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Millipore mefloquine hydrochloride
Pharmacological characterization of MoNNet neuronal and network activity. a Characterization of MoNNet functional properties by pharmacological treatments with GABAergic and Glutamatergic synaptic inhibitors: Bicuculine [10 μM], Picrotoxin[10 μM], D-APV [40 μM] and NBQX [10 μM]), and ionic channel blockers: <t>Mefloquine</t> [25 μM], Nifedipine [10 μM] and TTX [1 μM]. Control samples were treated with the solvent DMSO alone. Y -axes quantify the increment relative to the baseline in same samples, after 1 h of treatments. Number of biological replicates ( n ) is shown on the plot. Blue and Orange bars are for MoNNets in phase I and II, respectively. Statistical significance was calculated by using one-way ANOVA and Dunnett multiple comparison test. * padj
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Images

1) Product Images from "An in vitro model of neuronal ensembles"

Article Title: An in vitro model of neuronal ensembles

Journal: Nature Communications

doi: 10.1038/s41467-022-31073-1

Pharmacological characterization of MoNNet neuronal and network activity. a Characterization of MoNNet functional properties by pharmacological treatments with GABAergic and Glutamatergic synaptic inhibitors: Bicuculine [10 μM], Picrotoxin[10 μM], D-APV [40 μM] and NBQX [10 μM]), and ionic channel blockers: Mefloquine [25 μM], Nifedipine [10 μM] and TTX [1 μM]. Control samples were treated with the solvent DMSO alone. Y -axes quantify the increment relative to the baseline in same samples, after 1 h of treatments. Number of biological replicates ( n ) is shown on the plot. Blue and Orange bars are for MoNNets in phase I and II, respectively. Statistical significance was calculated by using one-way ANOVA and Dunnett multiple comparison test. * padj
Figure Legend Snippet: Pharmacological characterization of MoNNet neuronal and network activity. a Characterization of MoNNet functional properties by pharmacological treatments with GABAergic and Glutamatergic synaptic inhibitors: Bicuculine [10 μM], Picrotoxin[10 μM], D-APV [40 μM] and NBQX [10 μM]), and ionic channel blockers: Mefloquine [25 μM], Nifedipine [10 μM] and TTX [1 μM]. Control samples were treated with the solvent DMSO alone. Y -axes quantify the increment relative to the baseline in same samples, after 1 h of treatments. Number of biological replicates ( n ) is shown on the plot. Blue and Orange bars are for MoNNets in phase I and II, respectively. Statistical significance was calculated by using one-way ANOVA and Dunnett multiple comparison test. * padj

Techniques Used: Activity Assay, Functional Assay

2) Product Images from "Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive Compounds"

Article Title: Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive Compounds

Journal: Membranes

doi: 10.3390/membranes11120943

Superoxide production induced by action of antimalarials on MRC, expressed as percentages of stimulation over basal activity in absence of drug, in absence and presence of dUQ transporter. ( A ) Superoxide formation induced by atovaquone; ( B ) Superoxide formation induced by quinidine; ( C ) Superoxide formation induced by mefloquine; ( D ) Superoxide formation induced by doxycycline; ( E ) Superoxide formation induced by artemisin; ( F ) Superoxide formation induced by tafenoquine. ANOVA statistical test * p
Figure Legend Snippet: Superoxide production induced by action of antimalarials on MRC, expressed as percentages of stimulation over basal activity in absence of drug, in absence and presence of dUQ transporter. ( A ) Superoxide formation induced by atovaquone; ( B ) Superoxide formation induced by quinidine; ( C ) Superoxide formation induced by mefloquine; ( D ) Superoxide formation induced by doxycycline; ( E ) Superoxide formation induced by artemisin; ( F ) Superoxide formation induced by tafenoquine. ANOVA statistical test * p

Techniques Used: Activity Assay

3) Product Images from "Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma"

Article Title: Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma

Journal: PLoS Neglected Tropical Diseases

doi: 10.1371/journal.pntd.0009511

In vitro schistosomula assays (step 1). Dot plot of individual IC50 values of 12 drugs and mefloquine control is shown. Each compound was tested in 3 independent, in vitro schistosomula experiments (except for MQ, N = 9) and individual IC50s (filled circles) are shown. Viability of schistosomula after 7 days drug exposure was assessed by microscopy. For four drugs (atovaquone, cycloguanil, doxycycline, clindamycin) the IC50 could not be calculated as no inhibition was observed. The IC50 is given in μM. Bar and lines indicate median IC50 and IQR. Dotted line: Threshold for drug activity is an IC50
Figure Legend Snippet: In vitro schistosomula assays (step 1). Dot plot of individual IC50 values of 12 drugs and mefloquine control is shown. Each compound was tested in 3 independent, in vitro schistosomula experiments (except for MQ, N = 9) and individual IC50s (filled circles) are shown. Viability of schistosomula after 7 days drug exposure was assessed by microscopy. For four drugs (atovaquone, cycloguanil, doxycycline, clindamycin) the IC50 could not be calculated as no inhibition was observed. The IC50 is given in μM. Bar and lines indicate median IC50 and IQR. Dotted line: Threshold for drug activity is an IC50

Techniques Used: In Vitro, Microscopy, Inhibition, Activity Assay

4) Product Images from "Action of mefloquine/amitriptyline THN101 combination on neuropathic mechanical hypersensitivity in mice"

Article Title: Action of mefloquine/amitriptyline THN101 combination on neuropathic mechanical hypersensitivity in mice

Journal: Pain

doi: 10.1097/j.pain.0000000000002276

Effect of amitriptyline and mefloquine combination on mechanical hypersensitivity in mice with neuropathic pain. The mechanical right hind paw withdrawal threshold (PWT) was assessed with von Frey filaments before surgery (B: baseline), the mean of postsurgical values before treatment is displayed as PS (postsurgery baseline), and the oral drug treatment was performed 2 to 3 weeks after surgery. On the drug treatment day, sham (n=8-11) and cuff (n=7-15 per group) mice were tested before and from 1 to 7 hours after drug administration. Mice PWT was assessed after amitriptyline (A) or mefloquine (B) treatment at different doses and after treatment with amitriptyline and mefloquine combination (C-F). Comparison of areas under the curve (AUC) between cuff VEH, mefloquine, amitriptyline, and THN101 (AMI 10 mg/kg/MEF 0.1 mg/kg)-treated groups are shown with whisker boxes (G). Vehicle solution (NaCl 0.9%, DMSO 0.02% 10 mL/kg p.o., once after time 0 test) was used as negative control (A to G). Results are expressed as mean ± SEM. Symbols for some of the post hoc comparisons: * P
Figure Legend Snippet: Effect of amitriptyline and mefloquine combination on mechanical hypersensitivity in mice with neuropathic pain. The mechanical right hind paw withdrawal threshold (PWT) was assessed with von Frey filaments before surgery (B: baseline), the mean of postsurgical values before treatment is displayed as PS (postsurgery baseline), and the oral drug treatment was performed 2 to 3 weeks after surgery. On the drug treatment day, sham (n=8-11) and cuff (n=7-15 per group) mice were tested before and from 1 to 7 hours after drug administration. Mice PWT was assessed after amitriptyline (A) or mefloquine (B) treatment at different doses and after treatment with amitriptyline and mefloquine combination (C-F). Comparison of areas under the curve (AUC) between cuff VEH, mefloquine, amitriptyline, and THN101 (AMI 10 mg/kg/MEF 0.1 mg/kg)-treated groups are shown with whisker boxes (G). Vehicle solution (NaCl 0.9%, DMSO 0.02% 10 mL/kg p.o., once after time 0 test) was used as negative control (A to G). Results are expressed as mean ± SEM. Symbols for some of the post hoc comparisons: * P

Techniques Used: Mouse Assay, Whisker Assay, Negative Control

Central descending aminergic pathways are necessary to the action of THN101 and mefloquine. The mechanical hind paw withdrawal thresholds (PWTs) were assessed using von Frey filaments in mice 2 to 4 weeks after cuff or sham surgery. Peripheral (A) and central (B–D) lesions were performed before surgery. In separate sets of experiments, cohorts of saline-treated and guanethidine-treated cuff mice were tested for response to vehicle and THN101 a week apart (A), cohorts of saline-treated and 6-OHDA-treated cuff mice were tested for response to vehicle and THN101 a week apart (B), cohorts of saline-treated and 6-OHDA-treated sham mice were tested for response to vehicle, THN101, and mefloquine (0.4 mg/kg) a week apart (C), and cohorts of saline-treated and 6-OHDA-treated cuff mice were tested for response to vehicle and mefloquine a week apart (D). Mice were tested before (0) and from 1 to 7 hours after drug administration. Results are expressed as mean ± SEM. Symbols for some of the post hoc comparisons: § P
Figure Legend Snippet: Central descending aminergic pathways are necessary to the action of THN101 and mefloquine. The mechanical hind paw withdrawal thresholds (PWTs) were assessed using von Frey filaments in mice 2 to 4 weeks after cuff or sham surgery. Peripheral (A) and central (B–D) lesions were performed before surgery. In separate sets of experiments, cohorts of saline-treated and guanethidine-treated cuff mice were tested for response to vehicle and THN101 a week apart (A), cohorts of saline-treated and 6-OHDA-treated cuff mice were tested for response to vehicle and THN101 a week apart (B), cohorts of saline-treated and 6-OHDA-treated sham mice were tested for response to vehicle, THN101, and mefloquine (0.4 mg/kg) a week apart (C), and cohorts of saline-treated and 6-OHDA-treated cuff mice were tested for response to vehicle and mefloquine a week apart (D). Mice were tested before (0) and from 1 to 7 hours after drug administration. Results are expressed as mean ± SEM. Symbols for some of the post hoc comparisons: § P

Techniques Used: Mouse Assay

Spinal action of mefloquine in THN101 combination. The experiment was conducted in cuff mice. The mechanical hind paw withdrawal thresholds (PWTs) were assessed using von Frey filaments in mice 2 to 3 weeks after cuff surgery. Central (i.t.) administration of mefloquine combined or not with oral administration of amitriptyline (10 mg/kg) was tested and monitored since 7hours after drug administration. Results are expressed as mean ± SEM. Symbols for some of the post hoc comparisons: * P
Figure Legend Snippet: Spinal action of mefloquine in THN101 combination. The experiment was conducted in cuff mice. The mechanical hind paw withdrawal thresholds (PWTs) were assessed using von Frey filaments in mice 2 to 3 weeks after cuff surgery. Central (i.t.) administration of mefloquine combined or not with oral administration of amitriptyline (10 mg/kg) was tested and monitored since 7hours after drug administration. Results are expressed as mean ± SEM. Symbols for some of the post hoc comparisons: * P

Techniques Used: Mouse Assay

Evaluation of mefloquine, amitriptyline, and nortriptyline concentrations by mass spectrometry after amitriptyline or THN101 treatment. Measures were performed only in cuff mice. Mefloquine, amitriptyline, and nortriptyline concentrations (nM) were measured in blood from 1 to 7 hours after amitriptyline (10 mg/kg) or THN101 (AMI 10 mg/kg/MEF 0.1 mg/kg) per os treatment. Results are expressed as mean ± SEM (A). Mefloquine, amitriptyline, and nortriptyline plasma concentrations (nM) (B), and spinal cord (C) and brain (D) concentrations (pmol/mg of protein) were also assessed 7 hours after amitriptyline or THN101 per os treatment (whisker boxes).
Figure Legend Snippet: Evaluation of mefloquine, amitriptyline, and nortriptyline concentrations by mass spectrometry after amitriptyline or THN101 treatment. Measures were performed only in cuff mice. Mefloquine, amitriptyline, and nortriptyline concentrations (nM) were measured in blood from 1 to 7 hours after amitriptyline (10 mg/kg) or THN101 (AMI 10 mg/kg/MEF 0.1 mg/kg) per os treatment. Results are expressed as mean ± SEM (A). Mefloquine, amitriptyline, and nortriptyline plasma concentrations (nM) (B), and spinal cord (C) and brain (D) concentrations (pmol/mg of protein) were also assessed 7 hours after amitriptyline or THN101 per os treatment (whisker boxes).

Techniques Used: Mass Spectrometry, Mouse Assay, Whisker Assay

THN101 action on mechanical hypersensitivity. Experiments were conducted in cuff mice. The mechanical right hind paw withdrawal threshold (PWT) was assessed with von Frey filaments before surgery (B: baseline), the mean of postsurgical values before treatment is displayed as PS (postsurgery baseline), and the drug treatment was performed or started 2 to 3 weeks after surgery. Treatments were given orally in the evening, and mice tested on the following day. In a first experiment, time course of THN101 (amitriptyline 10 mg/kg/mefloquine 0.1 mg/kg) action was compared with control, amitriptyline, and mefloquine treatments (A). In a second experiment, THN101 was orally given each evening over 5 consecutive days, and mice tested each time 12 hours postadministration (B). Results are expressed as mean ± SEM. Symbols for some of the post hoc comparisons: * P
Figure Legend Snippet: THN101 action on mechanical hypersensitivity. Experiments were conducted in cuff mice. The mechanical right hind paw withdrawal threshold (PWT) was assessed with von Frey filaments before surgery (B: baseline), the mean of postsurgical values before treatment is displayed as PS (postsurgery baseline), and the drug treatment was performed or started 2 to 3 weeks after surgery. Treatments were given orally in the evening, and mice tested on the following day. In a first experiment, time course of THN101 (amitriptyline 10 mg/kg/mefloquine 0.1 mg/kg) action was compared with control, amitriptyline, and mefloquine treatments (A). In a second experiment, THN101 was orally given each evening over 5 consecutive days, and mice tested each time 12 hours postadministration (B). Results are expressed as mean ± SEM. Symbols for some of the post hoc comparisons: * P

Techniques Used: Mouse Assay

In vitro evaluation of mefloquine pharmacological potential targets. In vitro determination of pharmacological targets of mefloquine at 1 µM (A). Binding and functional properties of mefloquine on relevant adenosine and serotonin targets (B). α1, alpha 1 adrenoceptor; α2, alpha 2 adrenoceptor; β1, beta 1 adrenoceptor; β2, beta 2 adrenoceptor; A1, adenosine receptor A1; A2A, adenosine receptor A2A; A3, adenosine receptor A3; DPCPX, 8-cyclopentyl-1,3-dipropylxanthine; CPA, N6-cyclopentyladenosine; NECA, 59-N-ethylcarboxamidoadenosine.
Figure Legend Snippet: In vitro evaluation of mefloquine pharmacological potential targets. In vitro determination of pharmacological targets of mefloquine at 1 µM (A). Binding and functional properties of mefloquine on relevant adenosine and serotonin targets (B). α1, alpha 1 adrenoceptor; α2, alpha 2 adrenoceptor; β1, beta 1 adrenoceptor; β2, beta 2 adrenoceptor; A1, adenosine receptor A1; A2A, adenosine receptor A2A; A3, adenosine receptor A3; DPCPX, 8-cyclopentyl-1,3-dipropylxanthine; CPA, N6-cyclopentyladenosine; NECA, 59-N-ethylcarboxamidoadenosine.

Techniques Used: In Vitro, Binding Assay, Functional Assay

In vivo evaluation of mefloquine pharmacological potential targets. All experiments were conducted in cuff mice. The mechanical right hind paw withdrawal threshold (PWT) was assessed with von Frey filaments. We tested the role of α 2 adrenoceptors in mefloquine action using yohimbine (YOH) (A) (* P
Figure Legend Snippet: In vivo evaluation of mefloquine pharmacological potential targets. All experiments were conducted in cuff mice. The mechanical right hind paw withdrawal threshold (PWT) was assessed with von Frey filaments. We tested the role of α 2 adrenoceptors in mefloquine action using yohimbine (YOH) (A) (* P

Techniques Used: In Vivo, Mouse Assay

5) Product Images from "Connexin-36-expressing Gap Junctions in VTA GABA Neurons Sustain Opiate Dependence"

Article Title: Connexin-36-expressing Gap Junctions in VTA GABA Neurons Sustain Opiate Dependence

Journal: bioRxiv

doi: 10.1101/2020.12.18.423554

Pharmacological blockade of VTA Cx36 spares LiCl CPA and somatic opiate withdrawal signs in rats. (A) Rats spent less time in a previously LiCl-paired compartment compared to a previously vehicle-paired compartment irrespective of whether they were DMSO-or mefloquine-pretreated (two-tailed t-test; t(6)=0.1387, p=0.8942; n =8). Bars represent the mean difference in time spent in the LiCl-paired compartment minus the vehicle-paired compartment. Error bars represent ± SEM. (B) Drug-naïve mice exhibited no somatic withdrawal signs at any timepoint following the last heroin injection, which was administered after a 5-day period of heroin administration. By contrast, ODW mice did exhibit somatic signs16 and 21 hours following the last heroin administration, irrespective of whether they were DMSO-or mefloquine-pretreated. As such, we saw significant effects of time ( F (2,60) =9.669, p=0.0002), I.C. pretreatment ( F (3,60) =20.11, p
Figure Legend Snippet: Pharmacological blockade of VTA Cx36 spares LiCl CPA and somatic opiate withdrawal signs in rats. (A) Rats spent less time in a previously LiCl-paired compartment compared to a previously vehicle-paired compartment irrespective of whether they were DMSO-or mefloquine-pretreated (two-tailed t-test; t(6)=0.1387, p=0.8942; n =8). Bars represent the mean difference in time spent in the LiCl-paired compartment minus the vehicle-paired compartment. Error bars represent ± SEM. (B) Drug-naïve mice exhibited no somatic withdrawal signs at any timepoint following the last heroin injection, which was administered after a 5-day period of heroin administration. By contrast, ODW mice did exhibit somatic signs16 and 21 hours following the last heroin administration, irrespective of whether they were DMSO-or mefloquine-pretreated. As such, we saw significant effects of time ( F (2,60) =9.669, p=0.0002), I.C. pretreatment ( F (3,60) =20.11, p

Techniques Used: Two Tailed Test, Mouse Assay, Injection

Pharmacological blockade of VTA Cx36 reverts ODW rats to a drug-naïve motivational state (A) Schematic of morphine CPP experiments in rats (created with BioRender.com). (B-F) Morphine CPP and opiate withdrawal CPA bar graphs where bars represent the mean difference in time spent in the morphine-paired compartment minus the vehicle-paired compartment, and the mean difference in time spent in the withdrawal-paired compartment minus the neutral compartment, respectively. (B) Morphine CPP difference scores for PBS-pretreated drug-naïve and ODW rats receiving intracranial DMSO or mefloquine ( n =6 per group). CPP difference scores were calculated as time spent in the morphine-paired compartment minus the time spent in the PBS-paired compartment. Rats exhibited morphine CPP irrespective of the I.C. pretreatment and motivational state, as there was no significant effect of motivational state (two-way ANOVA; F (1,20) =0.545, p=0.468), I.C. pretreatment ( F (1,20) =0.034, p=0.853) nor the motivational state × I.C pretreatment interaction ( F (1,20) =0.008, p=0.929, n =24). (C) Morphine CPP difference scores for α-flu-pretreated drug-naïve and ODW rats receiving intracranial DMSO or mefloquine ( n =6 per group). We saw a significant interaction of motivational state × I.C. pretreatment ( F (1,20) =10.26, p=0.0045, n =24) where α-flu blocked preferences in DMSO-pretreated ODW rats but not in mefloquine-pretreated ODW rats (two-tailed t-test; t (10) =4.803, p=0.0007, n =12). (D) Morphine CPP difference scores for TPP inactivation experiments wherein rats subjected to opiate dependence and withdrawal received PBS or lidocaine i nto the TPP, and DMSO or mefloquine into the VTA ( n =30). We saw a significant VTA pretreatment × TPP pretreatment interaction ( F (1,21)=6.943, p=0.0155, n =25). A significant difference was found between rats that received TPP lidocaine and VTA mefloquine vs. rats that received TPP PBS and VTA mefloquine (two-tailed t-test; t (11) =2.764, p=0.0184, n =13). (E) CPA difference scores for opiate-withdrawn DMSO and mefloquine-pretreated rats. Unlike the DMSO-pretreated group, mefloquine-pretreated rats did not avoid the withdrawal-paired compartment (two-tailed t-test; t (21) =2.099, p= 0.0481, n =23). (F) Morphine CPP difference scores for PBS or α-flu-pretreated rats that either received intracranial furosemide or a cocktail of furosemide and mefloquine. We saw a significant interaction between I.C. pretreatment × systemic pretreatment ( F (1,41) =4.440, p=0.0413) where α-flu blocked CPP in the furosemide group but not in the furosemide + mefloquine group (two-tailed t-test; t (21) =2.772, p=0.0114, n =23). (G) Top: representative brain section depicting VTA cannulation following cresyl violet staining. Bottom: schematic of coronal brain sections (−5.30 and −5.60 posterior to bregma). Bilateral cannulae were used and therefore each red dot represents a single cannula tip and has a corresponding red dot on the contralateral side. Subjects were included only if both placements were within the boundaries of the VTA. Schematic depicts placements from mefloquine-pretreated ODW rats in Fig 3c . Drawings adapted from Paxinos Watson ( Paxinos and Watson, 2006 ). Data are represented as mean ± SEM. * denotes differences where p
Figure Legend Snippet: Pharmacological blockade of VTA Cx36 reverts ODW rats to a drug-naïve motivational state (A) Schematic of morphine CPP experiments in rats (created with BioRender.com). (B-F) Morphine CPP and opiate withdrawal CPA bar graphs where bars represent the mean difference in time spent in the morphine-paired compartment minus the vehicle-paired compartment, and the mean difference in time spent in the withdrawal-paired compartment minus the neutral compartment, respectively. (B) Morphine CPP difference scores for PBS-pretreated drug-naïve and ODW rats receiving intracranial DMSO or mefloquine ( n =6 per group). CPP difference scores were calculated as time spent in the morphine-paired compartment minus the time spent in the PBS-paired compartment. Rats exhibited morphine CPP irrespective of the I.C. pretreatment and motivational state, as there was no significant effect of motivational state (two-way ANOVA; F (1,20) =0.545, p=0.468), I.C. pretreatment ( F (1,20) =0.034, p=0.853) nor the motivational state × I.C pretreatment interaction ( F (1,20) =0.008, p=0.929, n =24). (C) Morphine CPP difference scores for α-flu-pretreated drug-naïve and ODW rats receiving intracranial DMSO or mefloquine ( n =6 per group). We saw a significant interaction of motivational state × I.C. pretreatment ( F (1,20) =10.26, p=0.0045, n =24) where α-flu blocked preferences in DMSO-pretreated ODW rats but not in mefloquine-pretreated ODW rats (two-tailed t-test; t (10) =4.803, p=0.0007, n =12). (D) Morphine CPP difference scores for TPP inactivation experiments wherein rats subjected to opiate dependence and withdrawal received PBS or lidocaine i nto the TPP, and DMSO or mefloquine into the VTA ( n =30). We saw a significant VTA pretreatment × TPP pretreatment interaction ( F (1,21)=6.943, p=0.0155, n =25). A significant difference was found between rats that received TPP lidocaine and VTA mefloquine vs. rats that received TPP PBS and VTA mefloquine (two-tailed t-test; t (11) =2.764, p=0.0184, n =13). (E) CPA difference scores for opiate-withdrawn DMSO and mefloquine-pretreated rats. Unlike the DMSO-pretreated group, mefloquine-pretreated rats did not avoid the withdrawal-paired compartment (two-tailed t-test; t (21) =2.099, p= 0.0481, n =23). (F) Morphine CPP difference scores for PBS or α-flu-pretreated rats that either received intracranial furosemide or a cocktail of furosemide and mefloquine. We saw a significant interaction between I.C. pretreatment × systemic pretreatment ( F (1,41) =4.440, p=0.0413) where α-flu blocked CPP in the furosemide group but not in the furosemide + mefloquine group (two-tailed t-test; t (21) =2.772, p=0.0114, n =23). (G) Top: representative brain section depicting VTA cannulation following cresyl violet staining. Bottom: schematic of coronal brain sections (−5.30 and −5.60 posterior to bregma). Bilateral cannulae were used and therefore each red dot represents a single cannula tip and has a corresponding red dot on the contralateral side. Subjects were included only if both placements were within the boundaries of the VTA. Schematic depicts placements from mefloquine-pretreated ODW rats in Fig 3c . Drawings adapted from Paxinos Watson ( Paxinos and Watson, 2006 ). Data are represented as mean ± SEM. * denotes differences where p

Techniques Used: Two Tailed Test, Staining

6) Product Images from "Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1"

Article Title: Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Journal: Neuroscience Bulletin

doi: 10.1007/s12264-020-00594-4

The Cx36 inhibitor mefloquine reverses the pT-ION-induced increase in expression of Cx36, GluK2, TRPA1, and p-ERK. A , B Cx36 (green) is co-localized with TRPA1 (red) in both the TG-V2 ( A ) and TG-V3 ( B ) in pT-ION mice (scale bars, 50 μm). DAPI was used to stain the cell nuclei. C–I The pT-ION–induced upregulation of Cx36, GluK2, TRPA1, and p-ERK in the ipsilateral TG is reversed by repeated application of the Cx36 inhibitor mefloquine (mef, 20 mg/kg, i.p. , once a day from day 7 to day 13 after pT-ION). Data are shown as means ± SEM, n = 7/group. ** P
Figure Legend Snippet: The Cx36 inhibitor mefloquine reverses the pT-ION-induced increase in expression of Cx36, GluK2, TRPA1, and p-ERK. A , B Cx36 (green) is co-localized with TRPA1 (red) in both the TG-V2 ( A ) and TG-V3 ( B ) in pT-ION mice (scale bars, 50 μm). DAPI was used to stain the cell nuclei. C–I The pT-ION–induced upregulation of Cx36, GluK2, TRPA1, and p-ERK in the ipsilateral TG is reversed by repeated application of the Cx36 inhibitor mefloquine (mef, 20 mg/kg, i.p. , once a day from day 7 to day 13 after pT-ION). Data are shown as means ± SEM, n = 7/group. ** P

Techniques Used: Expressing, Mouse Assay, Staining

7) Product Images from "Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo"

Article Title: Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo

Journal: Journal of Virology

doi: 10.1128/JVI.01218-20

Antiviral activity of additional FDA-approved compounds against SARS-CoV-2. Other drugs that showed antiviral activity in our initial CellTiter-Glo screening were tested for inhibition of productive virus infection. Cells were treated with the indicated concentrations of amodiaquine dihydrochloride dihydrate (A), amodiaquine hydrochloride (B), chlorpromazine (C), imatinib (D), and mefloquine (E) for 2 h prior to infection with SARS-CoV-2 at an MOI of 0.1 for 24 h. Supernatant was collected and used for TCID 50 assays to quantify infectious virus production. Data are from a representative experiment of four performed on triplicate wells. Data are means, with error bars indicating standard deviations. In all cases, t tests were performed for vehicle control versus drug-treated samples, *, P
Figure Legend Snippet: Antiviral activity of additional FDA-approved compounds against SARS-CoV-2. Other drugs that showed antiviral activity in our initial CellTiter-Glo screening were tested for inhibition of productive virus infection. Cells were treated with the indicated concentrations of amodiaquine dihydrochloride dihydrate (A), amodiaquine hydrochloride (B), chlorpromazine (C), imatinib (D), and mefloquine (E) for 2 h prior to infection with SARS-CoV-2 at an MOI of 0.1 for 24 h. Supernatant was collected and used for TCID 50 assays to quantify infectious virus production. Data are from a representative experiment of four performed on triplicate wells. Data are means, with error bars indicating standard deviations. In all cases, t tests were performed for vehicle control versus drug-treated samples, *, P

Techniques Used: Activity Assay, Inhibition, Infection

Antiviral activity of selected FDA-approved drugs in A549-hACE2 cells infected with SARS-CoV-2. A549-hACE2 cells were pretreated with hydroxychloroquine (HCQ), chloroquine (CQ), amodiaquine dihydrochloride dihydrate (AmD), amodiaquine hydrochloride (AmH), chlorpromazine (CPZ), imatinib (Imat), or mefloquine (Mefl) at the indicated concentrations for 2 h prior to infection with SARS-CoV-2 at MOI 0.1. At 48 hpi, supernatant was collected for titer determination by TCID 50 assay, and cells were collected in TRIzol for RNA extraction and qRT-PCR. qRT-PCR was carried out for the RdRp gene (A) and the N gene (B), and data are presented as fold change relative to vehicle control (0.1% H 2 O for HCQ and CQ and 0.1% DMSO for all other drugs), with RNA levels being normalized to GAPDH. Data are from a representative experiment of three performed in triplicate. Error bars indicate standard deviations. (C) Titers of virus produced from drug-treated and vehicle control cells, presented as TCID 50 /ml. Data are from three independent experiments performed in triplicate. Error bars indicate standard deviations. t tests were performed for vehicle control versus drug-treated samples, ****, P
Figure Legend Snippet: Antiviral activity of selected FDA-approved drugs in A549-hACE2 cells infected with SARS-CoV-2. A549-hACE2 cells were pretreated with hydroxychloroquine (HCQ), chloroquine (CQ), amodiaquine dihydrochloride dihydrate (AmD), amodiaquine hydrochloride (AmH), chlorpromazine (CPZ), imatinib (Imat), or mefloquine (Mefl) at the indicated concentrations for 2 h prior to infection with SARS-CoV-2 at MOI 0.1. At 48 hpi, supernatant was collected for titer determination by TCID 50 assay, and cells were collected in TRIzol for RNA extraction and qRT-PCR. qRT-PCR was carried out for the RdRp gene (A) and the N gene (B), and data are presented as fold change relative to vehicle control (0.1% H 2 O for HCQ and CQ and 0.1% DMSO for all other drugs), with RNA levels being normalized to GAPDH. Data are from a representative experiment of three performed in triplicate. Error bars indicate standard deviations. (C) Titers of virus produced from drug-treated and vehicle control cells, presented as TCID 50 /ml. Data are from three independent experiments performed in triplicate. Error bars indicate standard deviations. t tests were performed for vehicle control versus drug-treated samples, ****, P

Techniques Used: Activity Assay, Infection, RNA Extraction, Quantitative RT-PCR, Produced

8) Product Images from "The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies"

Article Title: The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies

Journal: eLife

doi: 10.7554/eLife.52707

Cascade of differential transcription factor activity. Connections between differentially active transcription factors in TM based on the MCF7 network. Each bubble represents a set of transcription factors that are differentially active in TM at a given timepoint. The codes on each bubble represent their differential activity status in Tamoxifen (first digit), Mefloquine, (second digit), and TM (third digit), where one is differentially active and 0 is not. Synergistic transcription factors in TM (001), are categorized into ‘explained’ bubbles (gray) or not explained (white). At each timepoint, synergistic transcription factors can be ‘explained’ by a network connection to a transcription factor that is differentially active in Tamoxifen and Mefloquine (111, magenta), or to at least one transcription factor in each of Tamoxifen alone (101, blue) and Mefloquine alone (011, red), or both, resulting in the left-hand, right-hand, and middle gray bubbles, respectively, in the middle layer. The fourth gray bubble in the lowest layer represents transcription factors which have connections to transcription factors in the middle ‘explained’ layer, but not to transcription factors in the top layer. Numbers in italics represent synergistic transcription factors that can be explained by connections to transcription factors that were active in monotherapies at the previous time point (blue, magenta, and red bubbled with dashed outlines at top of each timepoint). At the right in each time point, the dashed-outline bubble represents ‘explained’ transcription factors in the gray bubbles at the previous time point. Synergistic transcription factors not explained by other means which have a connection to any ‘explained’ transcription factors at the previous time point are shown in the gray bubble below the dashed-outline bubble. Finally, synergistic transcription factors that cannot be explained by any network connections are shown in the white bubble resulting from the ‘null’ set at each timepoint. The colors in this figure correspond to Figure 9 , and the sum of all gray bubbles at each timepoint in this figure correspond to the single gray bubble shown at each timepoint in Figure 9 . (See also Source data 10 ).
Figure Legend Snippet: Cascade of differential transcription factor activity. Connections between differentially active transcription factors in TM based on the MCF7 network. Each bubble represents a set of transcription factors that are differentially active in TM at a given timepoint. The codes on each bubble represent their differential activity status in Tamoxifen (first digit), Mefloquine, (second digit), and TM (third digit), where one is differentially active and 0 is not. Synergistic transcription factors in TM (001), are categorized into ‘explained’ bubbles (gray) or not explained (white). At each timepoint, synergistic transcription factors can be ‘explained’ by a network connection to a transcription factor that is differentially active in Tamoxifen and Mefloquine (111, magenta), or to at least one transcription factor in each of Tamoxifen alone (101, blue) and Mefloquine alone (011, red), or both, resulting in the left-hand, right-hand, and middle gray bubbles, respectively, in the middle layer. The fourth gray bubble in the lowest layer represents transcription factors which have connections to transcription factors in the middle ‘explained’ layer, but not to transcription factors in the top layer. Numbers in italics represent synergistic transcription factors that can be explained by connections to transcription factors that were active in monotherapies at the previous time point (blue, magenta, and red bubbled with dashed outlines at top of each timepoint). At the right in each time point, the dashed-outline bubble represents ‘explained’ transcription factors in the gray bubbles at the previous time point. Synergistic transcription factors not explained by other means which have a connection to any ‘explained’ transcription factors at the previous time point are shown in the gray bubble below the dashed-outline bubble. Finally, synergistic transcription factors that cannot be explained by any network connections are shown in the white bubble resulting from the ‘null’ set at each timepoint. The colors in this figure correspond to Figure 9 , and the sum of all gray bubbles at each timepoint in this figure correspond to the single gray bubble shown at each timepoint in Figure 9 . (See also Source data 10 ).

Techniques Used: Activity Assay

9) Product Images from "Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo"

Article Title: Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo

Journal: Parasites & Vectors

doi: 10.1186/s13071-020-04235-7

Course of parasitemia (mean ± standard deviation) in BALB/c mice inoculated with 1 × 10 7 Babesia microti and treated with either vehicle, artesunate (ARS) 25 mg/kg, mefloquine (MEF) 50 mg/kg, tafenoquine (TAF) 10 mg/kg (base), artesunate (ARS) 25 mg/kg + mefloquine (MEF) 50 mg/kg and artesunate (ARS) 25 mg/kg + tafenoquine (TAF) 10 mg/kg (base). ARS dissolved in 5% sodium bicarbonate was administered intraperitoneally, MEF dissolved in 20% ethanol in polyethylene glycol in water was given orally, and TAF dissolved in 10% DMSO in polyethylene glycol in water was given orally. ARS was given daily for 5 days starting at day 4 of infection (green arrows), and MEF or TAF were given in alternate days (days 4, 6 and 8: blue arrows). Parasitemia was checked by microscopy. Mice in both TAF groups showed lower levels of parasitemia on day 8 ( P = 0.0079 for all groups compared with each TAF group) and all mice cleared parasitemia on day 9. The parasitemia of the mice in the other groups (ARS alone or MEF) were not significantly different from the parasitemia in the vehicle group
Figure Legend Snippet: Course of parasitemia (mean ± standard deviation) in BALB/c mice inoculated with 1 × 10 7 Babesia microti and treated with either vehicle, artesunate (ARS) 25 mg/kg, mefloquine (MEF) 50 mg/kg, tafenoquine (TAF) 10 mg/kg (base), artesunate (ARS) 25 mg/kg + mefloquine (MEF) 50 mg/kg and artesunate (ARS) 25 mg/kg + tafenoquine (TAF) 10 mg/kg (base). ARS dissolved in 5% sodium bicarbonate was administered intraperitoneally, MEF dissolved in 20% ethanol in polyethylene glycol in water was given orally, and TAF dissolved in 10% DMSO in polyethylene glycol in water was given orally. ARS was given daily for 5 days starting at day 4 of infection (green arrows), and MEF or TAF were given in alternate days (days 4, 6 and 8: blue arrows). Parasitemia was checked by microscopy. Mice in both TAF groups showed lower levels of parasitemia on day 8 ( P = 0.0079 for all groups compared with each TAF group) and all mice cleared parasitemia on day 9. The parasitemia of the mice in the other groups (ARS alone or MEF) were not significantly different from the parasitemia in the vehicle group

Techniques Used: Standard Deviation, Mouse Assay, Infection, Microscopy

Body weight ( a ), hematocrit ( b ) and platelet counts ( c ) (mean ± standard deviation) of BALB/c mice inoculated with 1 × 10 7 Babesia microti and treated with either vehicle, artesunate (ARS) 25 mg/kg, mefloquine (MEF) 50 mg/kg, tafenoquine (TAF) 10 mg/kg (base), ARS 25 mg/kg + MEF 50 mg/kg and ARS 25 mg/kg + TAF 10 mg/kg (base) (5 mice per group). a There was no significant difference in body weight changes between groups during infection, and mice in all groups showed a 3–10% increase of weight at day 20. b Hematocrit decreased in all groups and on days 8 and 12 the TAF alone group showed hematocrit levels higher than the other groups ( P = 0.0317 compared to VEH group), except ARS + TAF group. The picture was similar on days 15 and 20, except that mice in the ARS only group had a recovery in hematocrit and showed no significant difference in relation to the TAF groups. c The profile of the platelet count decrease was similar to that of the hematocrit, decreasing in all groups on days 8 and 12 - the TAF alone group showed platelet counts higher than the other groups including the ARS + TAF group ( P = 0.079 and 0.0456 compared to VEH on days 8 and 12, respectively). On day 20, only the groups VEH ( P = 0.0159) and ARS + MEF ( P = 0.0079) showed platelet counts significantly lower than the TAF group
Figure Legend Snippet: Body weight ( a ), hematocrit ( b ) and platelet counts ( c ) (mean ± standard deviation) of BALB/c mice inoculated with 1 × 10 7 Babesia microti and treated with either vehicle, artesunate (ARS) 25 mg/kg, mefloquine (MEF) 50 mg/kg, tafenoquine (TAF) 10 mg/kg (base), ARS 25 mg/kg + MEF 50 mg/kg and ARS 25 mg/kg + TAF 10 mg/kg (base) (5 mice per group). a There was no significant difference in body weight changes between groups during infection, and mice in all groups showed a 3–10% increase of weight at day 20. b Hematocrit decreased in all groups and on days 8 and 12 the TAF alone group showed hematocrit levels higher than the other groups ( P = 0.0317 compared to VEH group), except ARS + TAF group. The picture was similar on days 15 and 20, except that mice in the ARS only group had a recovery in hematocrit and showed no significant difference in relation to the TAF groups. c The profile of the platelet count decrease was similar to that of the hematocrit, decreasing in all groups on days 8 and 12 - the TAF alone group showed platelet counts higher than the other groups including the ARS + TAF group ( P = 0.079 and 0.0456 compared to VEH on days 8 and 12, respectively). On day 20, only the groups VEH ( P = 0.0159) and ARS + MEF ( P = 0.0079) showed platelet counts significantly lower than the TAF group

Techniques Used: Standard Deviation, Mouse Assay, Infection

In vitro activity of artesunate (ARS) ( a ), mefloquine (MEF) ( b ), tafenoquine (TAF) ( c ), primaquine (PRI) ( d ) and methylene blue (MB) ( e ) against Babesia bovis . Results are expressed as % (mean ± standard deviation) of growth at each drug concentration in relation to wells without drug (100% growth) after 4 days of culture. In the MB graph ( e ), wells containing uninfected red blood cells (uRBC) were run in parallel for all MB concentrations, because MB causes a background fluorescence and this background value was subtracted from the corresponding wells containing infected red blood cells (iRBC) to generate the iRBC MB drug response curve. Numbers in boxes in each graph represent the IC 50 (in µm) for each given drug. Abbreviation : Conc (x-axis), concentration of the drug
Figure Legend Snippet: In vitro activity of artesunate (ARS) ( a ), mefloquine (MEF) ( b ), tafenoquine (TAF) ( c ), primaquine (PRI) ( d ) and methylene blue (MB) ( e ) against Babesia bovis . Results are expressed as % (mean ± standard deviation) of growth at each drug concentration in relation to wells without drug (100% growth) after 4 days of culture. In the MB graph ( e ), wells containing uninfected red blood cells (uRBC) were run in parallel for all MB concentrations, because MB causes a background fluorescence and this background value was subtracted from the corresponding wells containing infected red blood cells (iRBC) to generate the iRBC MB drug response curve. Numbers in boxes in each graph represent the IC 50 (in µm) for each given drug. Abbreviation : Conc (x-axis), concentration of the drug

Techniques Used: In Vitro, Activity Assay, Standard Deviation, Concentration Assay, Fluorescence, Infection

In vitro activity of mefloquine (MEF) ( a ), tafenoquine (TAF) ( b ), primaquine (PRI) ( c ) and methylene blue (MB) ( d ), alone or in combination with artesunate (ARS), against Babesia bovis . Drugs were combined in equimolar concentrations, except for methylene blue where the proportion for each well was 25:1 ARS:MB. Results are expressed as % of growth (mean ± standard deviation) at each drug concentration in relation to wells without drug (100% growth) after 4 days of culture. Abbreviation : Conc (x-axis), concentration of the drug
Figure Legend Snippet: In vitro activity of mefloquine (MEF) ( a ), tafenoquine (TAF) ( b ), primaquine (PRI) ( c ) and methylene blue (MB) ( d ), alone or in combination with artesunate (ARS), against Babesia bovis . Drugs were combined in equimolar concentrations, except for methylene blue where the proportion for each well was 25:1 ARS:MB. Results are expressed as % of growth (mean ± standard deviation) at each drug concentration in relation to wells without drug (100% growth) after 4 days of culture. Abbreviation : Conc (x-axis), concentration of the drug

Techniques Used: In Vitro, Activity Assay, Standard Deviation, Concentration Assay

Body weight ( a ), hematocrit ( b ) and platelet counts ( c ) (mean ± standard deviation) of the uninfected control (CTL) and BALB/c mice inoculated with 1 × 10 7 Babesia microti and treated with either vehicle, artesunate (ARS) 25 mg/kg, mefloquine (MEF) 10 mg/kg or 50 mg/kg, artesunate (ARS) 25 mg/kg + mefloquine (MEF) 10 mg/kg or 50 mg/kg (5 mice per group). a Infected mice receiving mefloquine 50 mg/kg in both groups showed discomfort after drug administration and were subjected to euthanasia by day 8. Infected mice in the other groups showed transient loss of weight at day 10, around the peak parasitemia, and then recovered, and there were no significant differences in body weight changes between the groups. Infected mice of all groups showed marked decreases in hematocrit ( b ) and platelet counts ( c ), but there were no significant differences between the groups
Figure Legend Snippet: Body weight ( a ), hematocrit ( b ) and platelet counts ( c ) (mean ± standard deviation) of the uninfected control (CTL) and BALB/c mice inoculated with 1 × 10 7 Babesia microti and treated with either vehicle, artesunate (ARS) 25 mg/kg, mefloquine (MEF) 10 mg/kg or 50 mg/kg, artesunate (ARS) 25 mg/kg + mefloquine (MEF) 10 mg/kg or 50 mg/kg (5 mice per group). a Infected mice receiving mefloquine 50 mg/kg in both groups showed discomfort after drug administration and were subjected to euthanasia by day 8. Infected mice in the other groups showed transient loss of weight at day 10, around the peak parasitemia, and then recovered, and there were no significant differences in body weight changes between the groups. Infected mice of all groups showed marked decreases in hematocrit ( b ) and platelet counts ( c ), but there were no significant differences between the groups

Techniques Used: Standard Deviation, Mouse Assay, Infection

Course of parasitemia (mean ± standard deviation) in BALB/c mice inoculated with 1 × 10 7 Babesia microti and treated with either vehicle, artesunate (ARS) 25 mg/kg, mefloquine (MEF) 10 mg/kg or 50 mg/kg, artesunate (ARS) 25 mg/kg + mefloquine (MEF) 10 mg/kg or 50 mg/kg (5 mice per group). Drugs were dissolved in 5% sodium bicarbonate (ARS) or 20% ethanol in polyethylene glycol in water (MEF) and administered intraperitoneally. ARS was given daily for 5 days starting at day 4 of infection (green arrows) and MEF was given in alternate days (days 4, 6 and 8: red arrows). Parasitemia was determined by microscopy. No significant differences in the course of parasitemia were observed between the groups
Figure Legend Snippet: Course of parasitemia (mean ± standard deviation) in BALB/c mice inoculated with 1 × 10 7 Babesia microti and treated with either vehicle, artesunate (ARS) 25 mg/kg, mefloquine (MEF) 10 mg/kg or 50 mg/kg, artesunate (ARS) 25 mg/kg + mefloquine (MEF) 10 mg/kg or 50 mg/kg (5 mice per group). Drugs were dissolved in 5% sodium bicarbonate (ARS) or 20% ethanol in polyethylene glycol in water (MEF) and administered intraperitoneally. ARS was given daily for 5 days starting at day 4 of infection (green arrows) and MEF was given in alternate days (days 4, 6 and 8: red arrows). Parasitemia was determined by microscopy. No significant differences in the course of parasitemia were observed between the groups

Techniques Used: Standard Deviation, Mouse Assay, Infection, Microscopy

10) Product Images from "Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo"

Article Title: Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo

Journal: bioRxiv

doi: 10.1101/2020.03.25.008482

Antiviral activity of additional FDA approved compounds against SARS-CoV-2. Other drugs that showed antiviral activity in our initial CellTiter-Glo screening were tested for inhibition of productive virus infection. Cells were treated with the indicated concentrations of A) amodiaquine dihydrochloride dihydrate, B) amodiaquine hydrochloride, C) chlorpromazine, D) mefloquine and E) imatinib for 2 h prior to infection with SARS-CoV-2 at MOI 0.1 for 24 h. Supernatant was collected and used for TCID 50 assay to quantify infectious virus production. Data are from a representative experiment of four performed on triplicate wells. Data are the mean TCID 50 /ml with error bars being standard deviation.
Figure Legend Snippet: Antiviral activity of additional FDA approved compounds against SARS-CoV-2. Other drugs that showed antiviral activity in our initial CellTiter-Glo screening were tested for inhibition of productive virus infection. Cells were treated with the indicated concentrations of A) amodiaquine dihydrochloride dihydrate, B) amodiaquine hydrochloride, C) chlorpromazine, D) mefloquine and E) imatinib for 2 h prior to infection with SARS-CoV-2 at MOI 0.1 for 24 h. Supernatant was collected and used for TCID 50 assay to quantify infectious virus production. Data are from a representative experiment of four performed on triplicate wells. Data are the mean TCID 50 /ml with error bars being standard deviation.

Techniques Used: Activity Assay, Inhibition, Infection, Standard Deviation

11) Product Images from "Some ototoxic drugs destroy cochlear support cells before damaging sensory hair cells"

Article Title: Some ototoxic drugs destroy cochlear support cells before damaging sensory hair cells

Journal: Neurotoxicity research

doi: 10.1007/s12640-020-00170-8

Representative photomicrographs illustrating the surface architecture of cochlear organotypic cultures approximately 40% of the distance from the base of the cochlea. Samples labeled with Acti-Stain Phalloidin 555 (Top row) which preferentially labels the actin in the stereocilia and cuticular plate of the three rows of outer hair cells (OHC), one row of inner hair cells (IHC) and the hexagonal borders of the supporting cells (SC) in the inner sulcus (IC) and outer sulcus (OS) region of the epithelium. Nuclei stained with To-Pro-3 (blue, middle row). Merge of phalloidin and To-Pro-3 in bottom row. (A1) Control specimens maintained in culture for 48 h. Note intense labeling of the apical pole of three orderly rows of OHC and single row of IHC and actin labeling of borders of SC in the inner sulcus (IS) and outer sulcus (OS) regions. Inset shows higher magnification view of the hexagonally borders of SC. Note thick actin border surrounding the SC and minimal actin labeling within the border. Scale bar 20 μm. (A2) Note To-Pro-3 of hair cells and support cells in deeper layer of organ of Corti. (A3) Merge of A1 and A2. (B1) Cochlear culture treated with 0.25 mM gentamicin (GM) for 24 h. Note massive loss of stereocilia and cuticular plate of OHC and IHC; missing hair cells surrounded by circumferential ring of actin arranged in orderly rows corresponding to the missing hair cells (inset with dashed border). Inset with solid border shows higher magnification view of apical surface of SC. Note weak labeling of actin borders of SC and diffuse labeling inside the SC border. (B2) Note To-Pro-3 labeled nuclei of SC. (B3) Merge of B1 and B2. (C1) Cochlear culture treated with 50 μM of cisplatin (CIS) for 48 h. Note massive loss of OHC and IHC, disorganized hair cell rows and minimal actin labeling in the SC regions. Cuticular plate of remaining hair cells shrunken or fragmented. (C2) Note paucity of To-Pro-3 labeled nuclei throughout organ of Corti. (C3) Merge of C1 and C2. (D1) Cochlear culture treated with 50 μM mefloquine (MEF) for 24 h. Many OHC and IHC missing; cuticular plate of remaining hair cells shrunken or fragmented and hair cell rows in disarray. Note minimal actin labeling in SC regions. (D2) Note paucity of To-Pro-3 labeled nuclei throughout organ of Corti. (D3) Merge of D1 and D2. (E1) Cochlear culture treated with 100 μM of cadmium (Cd) for 48 h. Hair cell rows in moderate disarray; many OHC and IHC missing. Minimal actin labeling in SC regions. (E2) Note lack of To-Pro-3 nuclear labeling throughout organ of Corti. (D3) Merge of D1 and D2.
Figure Legend Snippet: Representative photomicrographs illustrating the surface architecture of cochlear organotypic cultures approximately 40% of the distance from the base of the cochlea. Samples labeled with Acti-Stain Phalloidin 555 (Top row) which preferentially labels the actin in the stereocilia and cuticular plate of the three rows of outer hair cells (OHC), one row of inner hair cells (IHC) and the hexagonal borders of the supporting cells (SC) in the inner sulcus (IC) and outer sulcus (OS) region of the epithelium. Nuclei stained with To-Pro-3 (blue, middle row). Merge of phalloidin and To-Pro-3 in bottom row. (A1) Control specimens maintained in culture for 48 h. Note intense labeling of the apical pole of three orderly rows of OHC and single row of IHC and actin labeling of borders of SC in the inner sulcus (IS) and outer sulcus (OS) regions. Inset shows higher magnification view of the hexagonally borders of SC. Note thick actin border surrounding the SC and minimal actin labeling within the border. Scale bar 20 μm. (A2) Note To-Pro-3 of hair cells and support cells in deeper layer of organ of Corti. (A3) Merge of A1 and A2. (B1) Cochlear culture treated with 0.25 mM gentamicin (GM) for 24 h. Note massive loss of stereocilia and cuticular plate of OHC and IHC; missing hair cells surrounded by circumferential ring of actin arranged in orderly rows corresponding to the missing hair cells (inset with dashed border). Inset with solid border shows higher magnification view of apical surface of SC. Note weak labeling of actin borders of SC and diffuse labeling inside the SC border. (B2) Note To-Pro-3 labeled nuclei of SC. (B3) Merge of B1 and B2. (C1) Cochlear culture treated with 50 μM of cisplatin (CIS) for 48 h. Note massive loss of OHC and IHC, disorganized hair cell rows and minimal actin labeling in the SC regions. Cuticular plate of remaining hair cells shrunken or fragmented. (C2) Note paucity of To-Pro-3 labeled nuclei throughout organ of Corti. (C3) Merge of C1 and C2. (D1) Cochlear culture treated with 50 μM mefloquine (MEF) for 24 h. Many OHC and IHC missing; cuticular plate of remaining hair cells shrunken or fragmented and hair cell rows in disarray. Note minimal actin labeling in SC regions. (D2) Note paucity of To-Pro-3 labeled nuclei throughout organ of Corti. (D3) Merge of D1 and D2. (E1) Cochlear culture treated with 100 μM of cadmium (Cd) for 48 h. Hair cell rows in moderate disarray; many OHC and IHC missing. Minimal actin labeling in SC regions. (E2) Note lack of To-Pro-3 nuclear labeling throughout organ of Corti. (D3) Merge of D1 and D2.

Techniques Used: Labeling, Staining, Immunohistochemistry

12) Product Images from "The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies"

Article Title: The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies

Journal: bioRxiv

doi: 10.1101/846915

Cascade of Differential Transcription Factor Activity Connections between differentially active transcription factors in TM based on the MCF7 network. Each bubble represents a set of transcription factors that are differentially active in TM at a given timepoint. The codes on each bubble represent their differential activity status in Tamoxifen (first digit), Mefloquine, (second digit), and TM (third digit), where 1 is differentially active and 0 is not. Synergistic transcription factors in TM (001), are categorized into “explained” bubbles (gray) or not explained (white). At each timepoint, synergistic transcription factors can be “explained” by a network connection to a transcription factor that is differentially active in Tamoxifen and Mefloquine (111, magenta), or to at least one transcription factor in each of Tamoxifen alone (101, blue) and Mefloquine alone (011, red), or both, resulting in the left-hand, right-hand, and middle gray bubbles, respectively, in the middle layer. The fourth gray bubble in the lowest layer represents transcription factors which have connections to transcription factors in the middle “explained” layer, but not to transcription factors in the top layer. Numbers in italics represent synergistic transcription factors that can be explained by connections to transcription factors that were active in monotherapies at the previous time point (blue, magenta, and red bubbled with dashed outlines at top of each timepoint). At the right in each time point, the dashed-outline bubble represents “explained” transcription factors in the gray bubbles at the previous time point. Synergistic transcription factors not explained by other means which have a connection to any “explained” transcription factors at the previous time point are shown in the gray bubble below the dashed-outline bubble. Finally, synergistic transcription factors that cannot be explained by any network connections are shown in the white bubble resulting from the “null” set at each timepoint. The colors in this figure correspond to figure 7 , and the sum of all gray bubbles at each timepoint in this figure correspond to the single gray bubble shown at each timepoint in figure 7 .
Figure Legend Snippet: Cascade of Differential Transcription Factor Activity Connections between differentially active transcription factors in TM based on the MCF7 network. Each bubble represents a set of transcription factors that are differentially active in TM at a given timepoint. The codes on each bubble represent their differential activity status in Tamoxifen (first digit), Mefloquine, (second digit), and TM (third digit), where 1 is differentially active and 0 is not. Synergistic transcription factors in TM (001), are categorized into “explained” bubbles (gray) or not explained (white). At each timepoint, synergistic transcription factors can be “explained” by a network connection to a transcription factor that is differentially active in Tamoxifen and Mefloquine (111, magenta), or to at least one transcription factor in each of Tamoxifen alone (101, blue) and Mefloquine alone (011, red), or both, resulting in the left-hand, right-hand, and middle gray bubbles, respectively, in the middle layer. The fourth gray bubble in the lowest layer represents transcription factors which have connections to transcription factors in the middle “explained” layer, but not to transcription factors in the top layer. Numbers in italics represent synergistic transcription factors that can be explained by connections to transcription factors that were active in monotherapies at the previous time point (blue, magenta, and red bubbled with dashed outlines at top of each timepoint). At the right in each time point, the dashed-outline bubble represents “explained” transcription factors in the gray bubbles at the previous time point. Synergistic transcription factors not explained by other means which have a connection to any “explained” transcription factors at the previous time point are shown in the gray bubble below the dashed-outline bubble. Finally, synergistic transcription factors that cannot be explained by any network connections are shown in the white bubble resulting from the “null” set at each timepoint. The colors in this figure correspond to figure 7 , and the sum of all gray bubbles at each timepoint in this figure correspond to the single gray bubble shown at each timepoint in figure 7 .

Techniques Used: Activity Assay

The Transcriptomics of Drug Combinations Mirror their Phenotypic Characteristics A) Monotherapies and drug combinations used in the study. B) Workflow of molecular analysis of synergy. Starburst highlights the novel component of RNAseq analysis. Question mark denotes the focus of the study. C-H) Fold change over control of cell count for MCF7 cells (C-E) and LNCaP cells (F-H) treated with Tamoxifen and Mefloquine (C,F), Mefloquine and Withaferin (D,G), and Tamoxifen and Withaferin (E,H). Predicted viability is based on the Bliss model. Excess Over Bliss (EOB) ± Error EOB is given for the 12, 24, and 48 hr time points (see Methods). I) Average gene expression for each treatment and time point in the MCF7 combination experiments (covering 108 treatment and 18 DMSO samples). G) Principal component analysis of gene expression for the average over replicates at each treatment and time point in the MCF7 combination and dose experiments. (See also Table S1 , Figures S1 - 3 , and Source Data Files 1 and 3.)
Figure Legend Snippet: The Transcriptomics of Drug Combinations Mirror their Phenotypic Characteristics A) Monotherapies and drug combinations used in the study. B) Workflow of molecular analysis of synergy. Starburst highlights the novel component of RNAseq analysis. Question mark denotes the focus of the study. C-H) Fold change over control of cell count for MCF7 cells (C-E) and LNCaP cells (F-H) treated with Tamoxifen and Mefloquine (C,F), Mefloquine and Withaferin (D,G), and Tamoxifen and Withaferin (E,H). Predicted viability is based on the Bliss model. Excess Over Bliss (EOB) ± Error EOB is given for the 12, 24, and 48 hr time points (see Methods). I) Average gene expression for each treatment and time point in the MCF7 combination experiments (covering 108 treatment and 18 DMSO samples). G) Principal component analysis of gene expression for the average over replicates at each treatment and time point in the MCF7 combination and dose experiments. (See also Table S1 , Figures S1 - 3 , and Source Data Files 1 and 3.)

Techniques Used: Cell Counting, Expressing

13) Product Images from "The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies"

Article Title: The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies

Journal: bioRxiv

doi: 10.1101/846915

Cascade of Differential Transcription Factor Activity Connections between differentially active transcription factors in TM based on the MCF7 network. Each bubble represents a set of transcription factors that are differentially active in TM at a given timepoint. The codes on each bubble represent their differential activity status in Tamoxifen (first digit), Mefloquine, (second digit), and TM (third digit), where 1 is differentially active and 0 is not. Synergistic transcription factors in TM (001), are categorized into “explained” bubbles (gray) or not explained (white). At each timepoint, synergistic transcription factors can be “explained” by a network connection to a transcription factor that is differentially active in Tamoxifen and Mefloquine (111, magenta), or to at least one transcription factor in each of Tamoxifen alone (101, blue) and Mefloquine alone (011, red), or both, resulting in the left-hand, right-hand, and middle gray bubbles, respectively, in the middle layer. The fourth gray bubble in the lowest layer represents transcription factors which have connections to transcription factors in the middle “explained” layer, but not to transcription factors in the top layer. Numbers in italics represent synergistic transcription factors that can be explained by connections to transcription factors that were active in monotherapies at the previous time point (blue, magenta, and red bubbled with dashed outlines at top of each timepoint). At the right in each time point, the dashed-outline bubble represents “explained” transcription factors in the gray bubbles at the previous time point. Synergistic transcription factors not explained by other means which have a connection to any “explained” transcription factors at the previous time point are shown in the gray bubble below the dashed-outline bubble. Finally, synergistic transcription factors that cannot be explained by any network connections are shown in the white bubble resulting from the “null” set at each timepoint. The colors in this figure correspond to figure 7 , and the sum of all gray bubbles at each timepoint in this figure correspond to the single gray bubble shown at each timepoint in figure 7 .
Figure Legend Snippet: Cascade of Differential Transcription Factor Activity Connections between differentially active transcription factors in TM based on the MCF7 network. Each bubble represents a set of transcription factors that are differentially active in TM at a given timepoint. The codes on each bubble represent their differential activity status in Tamoxifen (first digit), Mefloquine, (second digit), and TM (third digit), where 1 is differentially active and 0 is not. Synergistic transcription factors in TM (001), are categorized into “explained” bubbles (gray) or not explained (white). At each timepoint, synergistic transcription factors can be “explained” by a network connection to a transcription factor that is differentially active in Tamoxifen and Mefloquine (111, magenta), or to at least one transcription factor in each of Tamoxifen alone (101, blue) and Mefloquine alone (011, red), or both, resulting in the left-hand, right-hand, and middle gray bubbles, respectively, in the middle layer. The fourth gray bubble in the lowest layer represents transcription factors which have connections to transcription factors in the middle “explained” layer, but not to transcription factors in the top layer. Numbers in italics represent synergistic transcription factors that can be explained by connections to transcription factors that were active in monotherapies at the previous time point (blue, magenta, and red bubbled with dashed outlines at top of each timepoint). At the right in each time point, the dashed-outline bubble represents “explained” transcription factors in the gray bubbles at the previous time point. Synergistic transcription factors not explained by other means which have a connection to any “explained” transcription factors at the previous time point are shown in the gray bubble below the dashed-outline bubble. Finally, synergistic transcription factors that cannot be explained by any network connections are shown in the white bubble resulting from the “null” set at each timepoint. The colors in this figure correspond to figure 7 , and the sum of all gray bubbles at each timepoint in this figure correspond to the single gray bubble shown at each timepoint in figure 7 .

Techniques Used: Activity Assay

The Transcriptomics of Drug Combinations Mirror their Phenotypic Characteristics A) Monotherapies and drug combinations used in the study. B) Workflow of molecular analysis of synergy. Starburst highlights the novel component of RNAseq analysis. Question mark denotes the focus of the study. C-H) Fold change over control of cell count for MCF7 cells (C-E) and LNCaP cells (F-H) treated with Tamoxifen and Mefloquine (C,F), Mefloquine and Withaferin (D,G), and Tamoxifen and Withaferin (E,H). Predicted viability is based on the Bliss model. Excess Over Bliss (EOB) ± Error EOB is given for the 12, 24, and 48 hr time points (see Methods). I) Average gene expression for each treatment and time point in the MCF7 combination experiments (covering 108 treatment and 18 DMSO samples). G) Principal component analysis of gene expression for the average over replicates at each treatment and time point in the MCF7 combination and dose experiments. (See also Table S1 , Figures S1 - 3 , and Source Data Files 1 and 3.)
Figure Legend Snippet: The Transcriptomics of Drug Combinations Mirror their Phenotypic Characteristics A) Monotherapies and drug combinations used in the study. B) Workflow of molecular analysis of synergy. Starburst highlights the novel component of RNAseq analysis. Question mark denotes the focus of the study. C-H) Fold change over control of cell count for MCF7 cells (C-E) and LNCaP cells (F-H) treated with Tamoxifen and Mefloquine (C,F), Mefloquine and Withaferin (D,G), and Tamoxifen and Withaferin (E,H). Predicted viability is based on the Bliss model. Excess Over Bliss (EOB) ± Error EOB is given for the 12, 24, and 48 hr time points (see Methods). I) Average gene expression for each treatment and time point in the MCF7 combination experiments (covering 108 treatment and 18 DMSO samples). G) Principal component analysis of gene expression for the average over replicates at each treatment and time point in the MCF7 combination and dose experiments. (See also Table S1 , Figures S1 - 3 , and Source Data Files 1 and 3.)

Techniques Used: Cell Counting, Expressing

14) Product Images from "Increased Th1 bias in memory T cells corresponds with protection from reinfection in Plasmodium infection, and is regulated by T cell-intrinsic STAT3"

Article Title: Increased Th1 bias in memory T cells corresponds with protection from reinfection in Plasmodium infection, and is regulated by T cell-intrinsic STAT3

Journal: bioRxiv

doi: 10.1101/724963

Response to P. chabaudi infection in drug-cured Bcl6, Blimp-1, and STAT3 TKO mice. TKO and WT animals were infected. Animals were given mefloquine (+MQ) starting on day 3 p.i. or left untreated (NTx). Splenocytes were harvested and analyzed by flow cytometry at day 7 p.i. (A) Contour plots show expression of IFN-γ and IL-21 in Teff. Bar graphs show average of fold change (%TKO/%WT) in a log2 scale of percentages of IFN-γ + IL-21 − and IFN-γ + IL-21 − Teff from NTx (black bars) and +MQ (white bars) from Bcl6 TKO (top), Blimp-1 TKO (middle), and STAT3 TKO (bottom). Intracellular cytokine staining in STAT3 TKO was the only one done with commercially prepared secretion inhibitor. (B) Contour plots show expression of PD-1 and CXCR5 in Teff from STAT3 TKO and WT mice. Bar graphs show percentages. Data representative of 2 experiments with 3 mice/group. † p
Figure Legend Snippet: Response to P. chabaudi infection in drug-cured Bcl6, Blimp-1, and STAT3 TKO mice. TKO and WT animals were infected. Animals were given mefloquine (+MQ) starting on day 3 p.i. or left untreated (NTx). Splenocytes were harvested and analyzed by flow cytometry at day 7 p.i. (A) Contour plots show expression of IFN-γ and IL-21 in Teff. Bar graphs show average of fold change (%TKO/%WT) in a log2 scale of percentages of IFN-γ + IL-21 − and IFN-γ + IL-21 − Teff from NTx (black bars) and +MQ (white bars) from Bcl6 TKO (top), Blimp-1 TKO (middle), and STAT3 TKO (bottom). Intracellular cytokine staining in STAT3 TKO was the only one done with commercially prepared secretion inhibitor. (B) Contour plots show expression of PD-1 and CXCR5 in Teff from STAT3 TKO and WT mice. Bar graphs show percentages. Data representative of 2 experiments with 3 mice/group. † p

Techniques Used: Infection, Mouse Assay, Flow Cytometry, Expressing, Staining

Drug-cured mice have fewer IFN-γ + IL-21 + CXCR5 + hybrid Th1/Tfh, and more IFN-γ + IL-21 − CXCR5 − Th1-like cells. C57BL/6J mice were infected, and one group was treated with mefloquine (MQ) starting day 3 and splenocytes were analyzed at day 7 p.i. (A) Parasitemia curve from not-treated (NTx, black filled circles) and treated (+MQ, open circles) groups. Arrows depict treatment days. (B) Bar graph shows CD4 Teff numbers in NTx (black) and +MQ (white) at day 7 p.i. (C) Contour plots show expression of PD-1 and CXCR5 and (D) IFN-γ and IL-21 in Teff. Bar graphs show percentages and numbers of Teff subsets. (E) Histogram shows CXCR5 expression in IFN-γ + IL-21 − Teff at day 7 p.i. Bar graph shows CXCR5 MFI (Mean Fluorescence Intensity) fold change over isotype control. (F) Boolean gating analysis of all possible combinations of CXCR5, IFN-γ and IL-21 expression by Teff. (G) Contour plots show expression of CD38 and GL-7 in B cells (B220 hi MHC-II hi ). Bar graph shows numbers of GC B cells. Data representative of 3 experiments with 3-4 mice/group.
Figure Legend Snippet: Drug-cured mice have fewer IFN-γ + IL-21 + CXCR5 + hybrid Th1/Tfh, and more IFN-γ + IL-21 − CXCR5 − Th1-like cells. C57BL/6J mice were infected, and one group was treated with mefloquine (MQ) starting day 3 and splenocytes were analyzed at day 7 p.i. (A) Parasitemia curve from not-treated (NTx, black filled circles) and treated (+MQ, open circles) groups. Arrows depict treatment days. (B) Bar graph shows CD4 Teff numbers in NTx (black) and +MQ (white) at day 7 p.i. (C) Contour plots show expression of PD-1 and CXCR5 and (D) IFN-γ and IL-21 in Teff. Bar graphs show percentages and numbers of Teff subsets. (E) Histogram shows CXCR5 expression in IFN-γ + IL-21 − Teff at day 7 p.i. Bar graph shows CXCR5 MFI (Mean Fluorescence Intensity) fold change over isotype control. (F) Boolean gating analysis of all possible combinations of CXCR5, IFN-γ and IL-21 expression by Teff. (G) Contour plots show expression of CD38 and GL-7 in B cells (B220 hi MHC-II hi ). Bar graph shows numbers of GC B cells. Data representative of 3 experiments with 3-4 mice/group.

Techniques Used: Mouse Assay, Infection, Expressing, Fluorescence

Day 5 mefloquine treatment has no effect on hybrid Th1/Tfh cell differentiation. C57BL/6J mice were infected, and one group was treated with mefloquine starting day 5 and splenocytes were analyzed at day 7 p.i. ( A ) Parasitemia on day 7 p.i. from untreated (NTx, black filled circles) and treated (+MQ, open circles) groups. Contour plots show expression of B ) PD-1 and CXCR5, and C) IFN-γ and IL-21 in Teff. Bar graphs show fraction of Teff and numbers of subsets. Data representative of 2 experiments with 3 mice/group.
Figure Legend Snippet: Day 5 mefloquine treatment has no effect on hybrid Th1/Tfh cell differentiation. C57BL/6J mice were infected, and one group was treated with mefloquine starting day 5 and splenocytes were analyzed at day 7 p.i. ( A ) Parasitemia on day 7 p.i. from untreated (NTx, black filled circles) and treated (+MQ, open circles) groups. Contour plots show expression of B ) PD-1 and CXCR5, and C) IFN-γ and IL-21 in Teff. Bar graphs show fraction of Teff and numbers of subsets. Data representative of 2 experiments with 3 mice/group.

Techniques Used: Cell Differentiation, Mouse Assay, Infection, Expressing

15) Product Images from "The Plasmodium falciparum cytoplasmic translation apparatus: a promising therapeutic target not yet exploited by clinically approved anti-malarials"

Article Title: The Plasmodium falciparum cytoplasmic translation apparatus: a promising therapeutic target not yet exploited by clinically approved anti-malarials

Journal: Malaria Journal

doi: 10.1186/s12936-018-2616-7

Dose-response curves of Pf growth, PfIVT, and RRIVT for mefloquine and controls. Dose-response curves comparing inhibition, calculated as % inhibition, of P. falciparum growth assay (black), P. falciparum in vitro translation assay (red), and commercially available rabbit reticulocyte in vitro translation assay (purple) for a cycloheximide, b DDD107498 (M5717), and c mefloquine. Name of compound, mechanism of action (where definitively known), and molecular structure are displayed at top of each graph
Figure Legend Snippet: Dose-response curves of Pf growth, PfIVT, and RRIVT for mefloquine and controls. Dose-response curves comparing inhibition, calculated as % inhibition, of P. falciparum growth assay (black), P. falciparum in vitro translation assay (red), and commercially available rabbit reticulocyte in vitro translation assay (purple) for a cycloheximide, b DDD107498 (M5717), and c mefloquine. Name of compound, mechanism of action (where definitively known), and molecular structure are displayed at top of each graph

Techniques Used: Inhibition, Growth Assay, In Vitro

16) Product Images from "Energy Stress-Mediated Cytotoxicity in Tuberous Sclerosis Complex 2-Deficient Cells with Nelfinavir and Mefloquine Treatment"

Article Title: Energy Stress-Mediated Cytotoxicity in Tuberous Sclerosis Complex 2-Deficient Cells with Nelfinavir and Mefloquine Treatment

Journal: Cancers

doi: 10.3390/cancers10100375

Mefloquine and nelfinavir drug combination causes increased ER stress in Tsc2 −/− MEFs. ( A ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with either DMSO, 1 µM thapsigargin (TPG), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV), or mefloquine and nelfinavir combination for 6 h, where indicated. Total protein levels of TSC2, IRE1α, ATF4, CHOP, GADD34, S6K1 and β-actin and S6K1 phosphorylated at Thr389 were detected by Western blot. ( B ) Xbp1 mRNA splicing was determined from the same treatments as described in ( A ). PCR products were resolved on agarose gels (unspliced = 480 bp upper band, spliced = 454 bp lower band). ( C – E ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with either DMSO or mefloquine and nelfinavir combination (MQ/NFV) for 6 h before being processed for RNA sequencing. A heat map for a panel of ER stress-linked genes is shown ( C ) and are graphed in ( D ). ( E ) Differences of mRNA expression between Tsc2 +/+ and Tsc2 −/− MEFs treated with mefloquine and nelfinavir is shown as a volcano plot and highlights ER stress genes. ( F ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with DMSO or mefloquine (MQ) and nelfinavir (NFV) combination for 6 h and 48 h. Total protein levels of ATF4, IRE-1α, GADD34, CHOP and β-actin were determined by Western blot.
Figure Legend Snippet: Mefloquine and nelfinavir drug combination causes increased ER stress in Tsc2 −/− MEFs. ( A ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with either DMSO, 1 µM thapsigargin (TPG), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV), or mefloquine and nelfinavir combination for 6 h, where indicated. Total protein levels of TSC2, IRE1α, ATF4, CHOP, GADD34, S6K1 and β-actin and S6K1 phosphorylated at Thr389 were detected by Western blot. ( B ) Xbp1 mRNA splicing was determined from the same treatments as described in ( A ). PCR products were resolved on agarose gels (unspliced = 480 bp upper band, spliced = 454 bp lower band). ( C – E ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with either DMSO or mefloquine and nelfinavir combination (MQ/NFV) for 6 h before being processed for RNA sequencing. A heat map for a panel of ER stress-linked genes is shown ( C ) and are graphed in ( D ). ( E ) Differences of mRNA expression between Tsc2 +/+ and Tsc2 −/− MEFs treated with mefloquine and nelfinavir is shown as a volcano plot and highlights ER stress genes. ( F ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with DMSO or mefloquine (MQ) and nelfinavir (NFV) combination for 6 h and 48 h. Total protein levels of ATF4, IRE-1α, GADD34, CHOP and β-actin were determined by Western blot.

Techniques Used: Western Blot, Polymerase Chain Reaction, RNA Sequencing Assay, Expressing

Mefloquine and nelfinavir drug cytotoxicity is not associated with mTORC1 hyperactivity and causes minimal autophagy inhibition. ( A ) Tsc2 −/− MEFs, NCI-H460, MCF7 and HCT116 cells were pre-treated with 50 nM rapamycin (RAP) for 1 h, where indicated, before being treated with 10 μM nelfinavir (NFV) and 10 µM mefloquine (MQ) for 48 h. Cells were stained with DRAQ7 and % cell death determined using flow cytometry. ( B ) Western blotting was carried out to determine rp-S6 phosphorylation at Ser235/236 in the cells treated in ( A ) after 48 h of treatment. ( C ) Tsc2 +/+ and Tsc2 −/− cells were treated with DMSO, 10 µM mefloquine (MQ), 20 µM chloroquine (CQ), 10 µM mefloquine or 20 µM chloroquine combined with 10 µM nelfinavir for 3 h. Accumulation of lipidated LC3-II were analyzed by Western blot. Total protein levels of β-actin were used as a loading control.
Figure Legend Snippet: Mefloquine and nelfinavir drug cytotoxicity is not associated with mTORC1 hyperactivity and causes minimal autophagy inhibition. ( A ) Tsc2 −/− MEFs, NCI-H460, MCF7 and HCT116 cells were pre-treated with 50 nM rapamycin (RAP) for 1 h, where indicated, before being treated with 10 μM nelfinavir (NFV) and 10 µM mefloquine (MQ) for 48 h. Cells were stained with DRAQ7 and % cell death determined using flow cytometry. ( B ) Western blotting was carried out to determine rp-S6 phosphorylation at Ser235/236 in the cells treated in ( A ) after 48 h of treatment. ( C ) Tsc2 +/+ and Tsc2 −/− cells were treated with DMSO, 10 µM mefloquine (MQ), 20 µM chloroquine (CQ), 10 µM mefloquine or 20 µM chloroquine combined with 10 µM nelfinavir for 3 h. Accumulation of lipidated LC3-II were analyzed by Western blot. Total protein levels of β-actin were used as a loading control.

Techniques Used: Inhibition, Staining, Flow Cytometry, Cytometry, Western Blot

Mefloquine and nelfinavir synergize to kill Tsc2 −/− Mouse embryonic fibroblasts (MEFs), ELT3-T3 and sporadic cancer cells. Dose response curves were performed in Tsc2 +/+ and Tsc2 −/− MEFs using flow cytometry to measure cell death following treatment with ( A ) nelfinavir (NFV); ( B ) mefloquine (MQ) and ( C ) combined mefloquine with a fixed concentration of 10 µM nelfinavir (MQ/NFV); ( D ) Tsc2 +/+ and Tsc2 −/− MEFs; ( E ) ELT3-T3 and ELT3-V3; ( F ) MCF7, HCT116 and NCI-H460 were treated with either DMSO, etoposide (ETO), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV) or mefloquine combined with nelfinavir (MQ/NFV) for 48 h. Cells were then tested by flow cytometry and cells were separated into viable and non-viable cell populations via DRAQ7 staining. Statistical significance is shown with combination treated Tsc2 −/− MEFs or the ELT3-V3 cells to their wild-type controls, and comparing single drug treatment of mefloquine and combination with the MCF7, HCT116 and NCI-H460.
Figure Legend Snippet: Mefloquine and nelfinavir synergize to kill Tsc2 −/− Mouse embryonic fibroblasts (MEFs), ELT3-T3 and sporadic cancer cells. Dose response curves were performed in Tsc2 +/+ and Tsc2 −/− MEFs using flow cytometry to measure cell death following treatment with ( A ) nelfinavir (NFV); ( B ) mefloquine (MQ) and ( C ) combined mefloquine with a fixed concentration of 10 µM nelfinavir (MQ/NFV); ( D ) Tsc2 +/+ and Tsc2 −/− MEFs; ( E ) ELT3-T3 and ELT3-V3; ( F ) MCF7, HCT116 and NCI-H460 were treated with either DMSO, etoposide (ETO), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV) or mefloquine combined with nelfinavir (MQ/NFV) for 48 h. Cells were then tested by flow cytometry and cells were separated into viable and non-viable cell populations via DRAQ7 staining. Statistical significance is shown with combination treated Tsc2 −/− MEFs or the ELT3-V3 cells to their wild-type controls, and comparing single drug treatment of mefloquine and combination with the MCF7, HCT116 and NCI-H460.

Techniques Used: Flow Cytometry, Cytometry, Concentration Assay, Staining

Mefloquine and nelfinavir prevents colony formation and spheroid growth. ( A ) Colony formation was tested in Tsc2 −/− MEFs seeded on soft agar that were treated for 14 days with Dimethyl Sulfoxide (DMSO), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV) or in combination. Tumor diameters were measured using Image J; scale bar is 200 μm. Significance was observed when comparing combined nelfinavir and mefloquine treatment to DMSO vehicle control. ( B ) Tsc2 −/− MEF spheroids were treated under the same conditions as ( A ) for 96 h. DRAQ7 was supplemented for the final 36 h to monitor cell death before images were taken and DRAQ7 fluorescence quantified. ( C ) Spheroids treated in ( B ) were re-plated onto standard tissue culture plates and grown in drug-free media. Images were taken every 24 h and the area of outgrowth calculated using Image J, scale bar is 200 μm and outgrowth area is graphed.
Figure Legend Snippet: Mefloquine and nelfinavir prevents colony formation and spheroid growth. ( A ) Colony formation was tested in Tsc2 −/− MEFs seeded on soft agar that were treated for 14 days with Dimethyl Sulfoxide (DMSO), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV) or in combination. Tumor diameters were measured using Image J; scale bar is 200 μm. Significance was observed when comparing combined nelfinavir and mefloquine treatment to DMSO vehicle control. ( B ) Tsc2 −/− MEF spheroids were treated under the same conditions as ( A ) for 96 h. DRAQ7 was supplemented for the final 36 h to monitor cell death before images were taken and DRAQ7 fluorescence quantified. ( C ) Spheroids treated in ( B ) were re-plated onto standard tissue culture plates and grown in drug-free media. Images were taken every 24 h and the area of outgrowth calculated using Image J, scale bar is 200 μm and outgrowth area is graphed.

Techniques Used: Fluorescence

17) Product Images from "Energy Stress-Mediated Cytotoxicity in Tuberous Sclerosis Complex 2-Deficient Cells with Nelfinavir and Mefloquine Treatment"

Article Title: Energy Stress-Mediated Cytotoxicity in Tuberous Sclerosis Complex 2-Deficient Cells with Nelfinavir and Mefloquine Treatment

Journal: Cancers

doi: 10.3390/cancers10100375

Mefloquine and nelfinavir drug combination causes increased ER stress in Tsc2 −/− MEFs. ( A ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with either DMSO, 1 µM thapsigargin (TPG), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV), or mefloquine and nelfinavir combination for 6 h, where indicated. Total protein levels of TSC2, IRE1α, ATF4, CHOP, GADD34, S6K1 and β-actin and S6K1 phosphorylated at Thr389 were detected by Western blot. ( B ) Xbp1 mRNA splicing was determined from the same treatments as described in ( A ). PCR products were resolved on agarose gels (unspliced = 480 bp upper band, spliced = 454 bp lower band). ( C – E ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with either DMSO or mefloquine and nelfinavir combination (MQ/NFV) for 6 h before being processed for RNA sequencing. A heat map for a panel of ER stress-linked genes is shown ( C ) and are graphed in ( D ). ( E ) Differences of mRNA expression between Tsc2 +/+ and Tsc2 −/− MEFs treated with mefloquine and nelfinavir is shown as a volcano plot and highlights ER stress genes. ( F ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with DMSO or mefloquine (MQ) and nelfinavir (NFV) combination for 6 h and 48 h. Total protein levels of ATF4, IRE-1α, GADD34, CHOP and β-actin were determined by Western blot.
Figure Legend Snippet: Mefloquine and nelfinavir drug combination causes increased ER stress in Tsc2 −/− MEFs. ( A ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with either DMSO, 1 µM thapsigargin (TPG), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV), or mefloquine and nelfinavir combination for 6 h, where indicated. Total protein levels of TSC2, IRE1α, ATF4, CHOP, GADD34, S6K1 and β-actin and S6K1 phosphorylated at Thr389 were detected by Western blot. ( B ) Xbp1 mRNA splicing was determined from the same treatments as described in ( A ). PCR products were resolved on agarose gels (unspliced = 480 bp upper band, spliced = 454 bp lower band). ( C – E ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with either DMSO or mefloquine and nelfinavir combination (MQ/NFV) for 6 h before being processed for RNA sequencing. A heat map for a panel of ER stress-linked genes is shown ( C ) and are graphed in ( D ). ( E ) Differences of mRNA expression between Tsc2 +/+ and Tsc2 −/− MEFs treated with mefloquine and nelfinavir is shown as a volcano plot and highlights ER stress genes. ( F ) Tsc2 +/+ and Tsc2 −/− MEFs were treated with DMSO or mefloquine (MQ) and nelfinavir (NFV) combination for 6 h and 48 h. Total protein levels of ATF4, IRE-1α, GADD34, CHOP and β-actin were determined by Western blot.

Techniques Used: Western Blot, Polymerase Chain Reaction, RNA Sequencing Assay, Expressing

Mefloquine and nelfinavir drug cytotoxicity is not associated with mTORC1 hyperactivity and causes minimal autophagy inhibition. ( A ) Tsc2 −/− MEFs, NCI-H460, MCF7 and HCT116 cells were pre-treated with 50 nM rapamycin (RAP) for 1 h, where indicated, before being treated with 10 μM nelfinavir (NFV) and 10 µM mefloquine (MQ) for 48 h. Cells were stained with DRAQ7 and % cell death determined using flow cytometry. ( B ) Western blotting was carried out to determine rp-S6 phosphorylation at Ser235/236 in the cells treated in ( A ) after 48 h of treatment. ( C ) Tsc2 +/+ and Tsc2 −/− cells were treated with DMSO, 10 µM mefloquine (MQ), 20 µM chloroquine (CQ), 10 µM mefloquine or 20 µM chloroquine combined with 10 µM nelfinavir for 3 h. Accumulation of lipidated LC3-II were analyzed by Western blot. Total protein levels of β-actin were used as a loading control.
Figure Legend Snippet: Mefloquine and nelfinavir drug cytotoxicity is not associated with mTORC1 hyperactivity and causes minimal autophagy inhibition. ( A ) Tsc2 −/− MEFs, NCI-H460, MCF7 and HCT116 cells were pre-treated with 50 nM rapamycin (RAP) for 1 h, where indicated, before being treated with 10 μM nelfinavir (NFV) and 10 µM mefloquine (MQ) for 48 h. Cells were stained with DRAQ7 and % cell death determined using flow cytometry. ( B ) Western blotting was carried out to determine rp-S6 phosphorylation at Ser235/236 in the cells treated in ( A ) after 48 h of treatment. ( C ) Tsc2 +/+ and Tsc2 −/− cells were treated with DMSO, 10 µM mefloquine (MQ), 20 µM chloroquine (CQ), 10 µM mefloquine or 20 µM chloroquine combined with 10 µM nelfinavir for 3 h. Accumulation of lipidated LC3-II were analyzed by Western blot. Total protein levels of β-actin were used as a loading control.

Techniques Used: Inhibition, Staining, Flow Cytometry, Western Blot

Mefloquine and nelfinavir synergize to kill Tsc2 −/− Mouse embryonic fibroblasts (MEFs), ELT3-T3 and sporadic cancer cells. Dose response curves were performed in Tsc2 +/+ and Tsc2 −/− MEFs using flow cytometry to measure cell death following treatment with ( A ) nelfinavir (NFV); ( B ) mefloquine (MQ) and ( C ) combined mefloquine with a fixed concentration of 10 µM nelfinavir (MQ/NFV); ( D ) Tsc2 +/+ and Tsc2 −/− MEFs; ( E ) ELT3-T3 and ELT3-V3; ( F ) MCF7, HCT116 and NCI-H460 were treated with either DMSO, etoposide (ETO), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV) or mefloquine combined with nelfinavir (MQ/NFV) for 48 h. Cells were then tested by flow cytometry and cells were separated into viable and non-viable cell populations via DRAQ7 staining. Statistical significance is shown with combination treated Tsc2 −/− MEFs or the ELT3-V3 cells to their wild-type controls, and comparing single drug treatment of mefloquine and combination with the MCF7, HCT116 and NCI-H460.
Figure Legend Snippet: Mefloquine and nelfinavir synergize to kill Tsc2 −/− Mouse embryonic fibroblasts (MEFs), ELT3-T3 and sporadic cancer cells. Dose response curves were performed in Tsc2 +/+ and Tsc2 −/− MEFs using flow cytometry to measure cell death following treatment with ( A ) nelfinavir (NFV); ( B ) mefloquine (MQ) and ( C ) combined mefloquine with a fixed concentration of 10 µM nelfinavir (MQ/NFV); ( D ) Tsc2 +/+ and Tsc2 −/− MEFs; ( E ) ELT3-T3 and ELT3-V3; ( F ) MCF7, HCT116 and NCI-H460 were treated with either DMSO, etoposide (ETO), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV) or mefloquine combined with nelfinavir (MQ/NFV) for 48 h. Cells were then tested by flow cytometry and cells were separated into viable and non-viable cell populations via DRAQ7 staining. Statistical significance is shown with combination treated Tsc2 −/− MEFs or the ELT3-V3 cells to their wild-type controls, and comparing single drug treatment of mefloquine and combination with the MCF7, HCT116 and NCI-H460.

Techniques Used: Flow Cytometry, Concentration Assay, Staining

Mefloquine and nelfinavir combined drug treatment induces cytotoxicity via energy stress in Tsc2 −/− MEFs. ( A ) The RNA sequencing data used for Figure 3 C−E was assessed for gene-expression of genes involved in energy homeostasis. A heatmap for a panel of energy stress-linked genes is shown. Differences of mRNA expression between Tsc2 +/+ and Tsc2 −/− MEFs treated with mefloquine and nelfinavir is shown as a volcano plot ( B ) and graphed ( C ). ( D ) Tsc2 −/− cells were treated with DMSO, 10 μM mefloquine and 10 μM nelfinavir combination (MQ/NFV) or mefloquine/nelfinavir combination with the addition of 8 mM methyl pyruvate (MQ/NFV/MP) for 48 h. Cells were then stained with DRAQ7 and % cell death determined by flow cytometry. ( E ) Tsc2 −/− were treated with either DMSO or 10 μM mefloquine and 10 μM nelfinavir combination in the presence or absence of 8 mM methyl pyruvate for 24 h and total and phosphorylated ACC and AMPK was determined by western blot. ( F ) Tsc2 +/+ and Tsc2 −/− cells were treated with either DMSO or 10 μM mefloquine and 10 μM nelfinavir combination in the presence or absence of 8 mM methyl pyruvate for 6 and 24 h, where indicated. Total protein levels of ACC, CHOP GADD34 and ATF4 as well as phosphorylated ACC were detected by Western blot.
Figure Legend Snippet: Mefloquine and nelfinavir combined drug treatment induces cytotoxicity via energy stress in Tsc2 −/− MEFs. ( A ) The RNA sequencing data used for Figure 3 C−E was assessed for gene-expression of genes involved in energy homeostasis. A heatmap for a panel of energy stress-linked genes is shown. Differences of mRNA expression between Tsc2 +/+ and Tsc2 −/− MEFs treated with mefloquine and nelfinavir is shown as a volcano plot ( B ) and graphed ( C ). ( D ) Tsc2 −/− cells were treated with DMSO, 10 μM mefloquine and 10 μM nelfinavir combination (MQ/NFV) or mefloquine/nelfinavir combination with the addition of 8 mM methyl pyruvate (MQ/NFV/MP) for 48 h. Cells were then stained with DRAQ7 and % cell death determined by flow cytometry. ( E ) Tsc2 −/− were treated with either DMSO or 10 μM mefloquine and 10 μM nelfinavir combination in the presence or absence of 8 mM methyl pyruvate for 24 h and total and phosphorylated ACC and AMPK was determined by western blot. ( F ) Tsc2 +/+ and Tsc2 −/− cells were treated with either DMSO or 10 μM mefloquine and 10 μM nelfinavir combination in the presence or absence of 8 mM methyl pyruvate for 6 and 24 h, where indicated. Total protein levels of ACC, CHOP GADD34 and ATF4 as well as phosphorylated ACC were detected by Western blot.

Techniques Used: RNA Sequencing Assay, Expressing, Staining, Flow Cytometry, Western Blot

Mefloquine and nelfinavir prevents colony formation and spheroid growth. ( A ) Colony formation was tested in Tsc2 −/− MEFs seeded on soft agar that were treated for 14 days with Dimethyl Sulfoxide (DMSO), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV) or in combination. Tumor diameters were measured using Image J; scale bar is 200 μm. Significance was observed when comparing combined nelfinavir and mefloquine treatment to DMSO vehicle control. ( B ) Tsc2 −/− MEF spheroids were treated under the same conditions as ( A ) for 96 h. DRAQ7 was supplemented for the final 36 h to monitor cell death before images were taken and DRAQ7 fluorescence quantified. ( C ) Spheroids treated in ( B ) were re-plated onto standard tissue culture plates and grown in drug-free media. Images were taken every 24 h and the area of outgrowth calculated using Image J, scale bar is 200 μm and outgrowth area is graphed.
Figure Legend Snippet: Mefloquine and nelfinavir prevents colony formation and spheroid growth. ( A ) Colony formation was tested in Tsc2 −/− MEFs seeded on soft agar that were treated for 14 days with Dimethyl Sulfoxide (DMSO), 10 µM mefloquine (MQ), 10 µM nelfinavir (NFV) or in combination. Tumor diameters were measured using Image J; scale bar is 200 μm. Significance was observed when comparing combined nelfinavir and mefloquine treatment to DMSO vehicle control. ( B ) Tsc2 −/− MEF spheroids were treated under the same conditions as ( A ) for 96 h. DRAQ7 was supplemented for the final 36 h to monitor cell death before images were taken and DRAQ7 fluorescence quantified. ( C ) Spheroids treated in ( B ) were re-plated onto standard tissue culture plates and grown in drug-free media. Images were taken every 24 h and the area of outgrowth calculated using Image J, scale bar is 200 μm and outgrowth area is graphed.

Techniques Used: Fluorescence

18) Product Images from "The Plasmodium falciparum cytoplasmic translation apparatus: a promising therapeutic target not yet exploited by clinically approved antimalarials"

Article Title: The Plasmodium falciparum cytoplasmic translation apparatus: a promising therapeutic target not yet exploited by clinically approved antimalarials

Journal: bioRxiv

doi: 10.1101/415513

Dose-response curves of Pf growth, PfIVT, and RRIVT for mefloquine and controls. Dose-response curves comparing inhibition, calculated as % inhibition, of P. falciparum growth assay (black), P. falciparum in vitro translation assay (red), and commercially available rabbit reticulocyte in vitro translation assay (purple). Name of compound, mechanism of action (where definitively known), and molecular structure are displayed at top of each graph.
Figure Legend Snippet: Dose-response curves of Pf growth, PfIVT, and RRIVT for mefloquine and controls. Dose-response curves comparing inhibition, calculated as % inhibition, of P. falciparum growth assay (black), P. falciparum in vitro translation assay (red), and commercially available rabbit reticulocyte in vitro translation assay (purple). Name of compound, mechanism of action (where definitively known), and molecular structure are displayed at top of each graph.

Techniques Used: Inhibition, Growth Assay, In Vitro

19) Product Images from "The Interactions of P-Glycoprotein with Antimalarial Drugs, Including Substrate Affinity, Inhibition and Regulation"

Article Title: The Interactions of P-Glycoprotein with Antimalarial Drugs, Including Substrate Affinity, Inhibition and Regulation

Journal: PLoS ONE

doi: 10.1371/journal.pone.0152677

A) Ap-Bas (solid square) and Bas-Ap (solid diamond) transport of mefloquine B). Ap-Bas (solid square) and Bas-Ap (solid diamond) transport of methylene blue alone and Ap-Bas (solid square with dots) plus Bas-Ap (hashed diamond) with PSC833 and Ap-Bas (open circle) plus Bas-Ap (hashed circle) with PSC833 combined with MK571
Figure Legend Snippet: A) Ap-Bas (solid square) and Bas-Ap (solid diamond) transport of mefloquine B). Ap-Bas (solid square) and Bas-Ap (solid diamond) transport of methylene blue alone and Ap-Bas (solid square with dots) plus Bas-Ap (hashed diamond) with PSC833 and Ap-Bas (open circle) plus Bas-Ap (hashed circle) with PSC833 combined with MK571

Techniques Used:

A) Western blot for 96 hours exposure of 20 μM antimalarials on Caco-2 cell monolayer. Beta actin was used as the reference protein. Lanes 1–15 were loaded with cell lysates of exposure 1)methylene blue, 2)mefloquine, 3)amodiaquine, 4)artesunate, 5)dihydroartemisinin, 6)artemisone, 7)0.5% ethanol, 8)artesunate plus mefloquine, 9)artesunate plus amodiaquine, 10)artemisone plus mefloquine, 11)artemisone plus amodiaquine, 12)dihydroartemisinin plus mefloquine, and 13)dihydroartemisinin plus amodiaquine 14) molecular weight marker 15) transfected Hela MDR1 positive control respectively. B) Regulation of P-gp transporter protein compared to control following 96 hours of antimalarial exposure on confluent Caco-2 cell monolayers.
Figure Legend Snippet: A) Western blot for 96 hours exposure of 20 μM antimalarials on Caco-2 cell monolayer. Beta actin was used as the reference protein. Lanes 1–15 were loaded with cell lysates of exposure 1)methylene blue, 2)mefloquine, 3)amodiaquine, 4)artesunate, 5)dihydroartemisinin, 6)artemisone, 7)0.5% ethanol, 8)artesunate plus mefloquine, 9)artesunate plus amodiaquine, 10)artemisone plus mefloquine, 11)artemisone plus amodiaquine, 12)dihydroartemisinin plus mefloquine, and 13)dihydroartemisinin plus amodiaquine 14) molecular weight marker 15) transfected Hela MDR1 positive control respectively. B) Regulation of P-gp transporter protein compared to control following 96 hours of antimalarial exposure on confluent Caco-2 cell monolayers.

Techniques Used: Western Blot, Molecular Weight, Marker, Transfection, Positive Control

A). Ap-Bas (striped square) and Bas-Ap (solid diamond) transport of rhodamine123 alone, Ap-Bas (hashed square) and Bas-Ap (open diamond) transport of rhodamine123 when combined with mefloquine B). Ap-Bas (hashed square) and Bas-Ap (open diamond) transport of rhodamine123 when combined with mefloquine compared to Ap-Bas (solid square) and Bas-Ap (hashed diamond) transport of rhodamine123 when co-incubated with mefloquine and artesunate (N = 3, Mean ±SEM)
Figure Legend Snippet: A). Ap-Bas (striped square) and Bas-Ap (solid diamond) transport of rhodamine123 alone, Ap-Bas (hashed square) and Bas-Ap (open diamond) transport of rhodamine123 when combined with mefloquine B). Ap-Bas (hashed square) and Bas-Ap (open diamond) transport of rhodamine123 when combined with mefloquine compared to Ap-Bas (solid square) and Bas-Ap (hashed diamond) transport of rhodamine123 when co-incubated with mefloquine and artesunate (N = 3, Mean ±SEM)

Techniques Used: Incubation

20) Product Images from "Behavioral effects of mefloquine in tail suspension and light/dark tests"

Article Title: Behavioral effects of mefloquine in tail suspension and light/dark tests

Journal: SpringerPlus

doi: 10.1186/s40064-015-1483-8

Behavior as a function of drug dose. a Emergence latency in the light dark test. b Rearing behavior in the light dark test. c Total time spent in the lighted area in the light dark test. d Total immobility time in the tail suspension test for Set 1 (0 vs. 5 mg/kg mefloquine). e Total immobility time in the tail suspension test for Set 2 (0 vs. 25 mg/kg mefloquine). f Total immobility time in the tail suspension test for Set 3 (0 vs. 100 mg/kg). All data is presented as M ± SEM. *Indicates a significant difference between indicated group and 0 mg/kg controls, p
Figure Legend Snippet: Behavior as a function of drug dose. a Emergence latency in the light dark test. b Rearing behavior in the light dark test. c Total time spent in the lighted area in the light dark test. d Total immobility time in the tail suspension test for Set 1 (0 vs. 5 mg/kg mefloquine). e Total immobility time in the tail suspension test for Set 2 (0 vs. 25 mg/kg mefloquine). f Total immobility time in the tail suspension test for Set 3 (0 vs. 100 mg/kg). All data is presented as M ± SEM. *Indicates a significant difference between indicated group and 0 mg/kg controls, p

Techniques Used:

21) Product Images from "Mefloquine in the nucleus accumbens promotes social avoidance and anxiety-like behavior in mice"

Article Title: Mefloquine in the nucleus accumbens promotes social avoidance and anxiety-like behavior in mice

Journal: Neuropharmacology

doi: 10.1016/j.neuropharm.2015.10.013

Direct infusion of mefloquine into nucleus accumbens promotes social avoidance behavior following subthreshold social defeat stress. (a) Schematic depicting bilateral cannula placements for all animals included in analysis (n=6–7 mice/group).
Figure Legend Snippet: Direct infusion of mefloquine into nucleus accumbens promotes social avoidance behavior following subthreshold social defeat stress. (a) Schematic depicting bilateral cannula placements for all animals included in analysis (n=6–7 mice/group).

Techniques Used: Mouse Assay

Single intraperitoneal injection of mefloquine promotes social avoidance behavior following subthreshold social defeat stress. (a) Experimental timeline. (b) Animals that received 20 mg/kg mefloquine prior to stress display decreased time in the interaction
Figure Legend Snippet: Single intraperitoneal injection of mefloquine promotes social avoidance behavior following subthreshold social defeat stress. (a) Experimental timeline. (b) Animals that received 20 mg/kg mefloquine prior to stress display decreased time in the interaction

Techniques Used: Injection

Direct infusion of mefloquine into ventral hippocampus has no effect on social avoidance behavior following subthreshold social defeat stress. (a) Schematic depicting bilateral cannula placements in the ventral hippocampus (n = 7–8 mice/group).
Figure Legend Snippet: Direct infusion of mefloquine into ventral hippocampus has no effect on social avoidance behavior following subthreshold social defeat stress. (a) Schematic depicting bilateral cannula placements in the ventral hippocampus (n = 7–8 mice/group).

Techniques Used: Mouse Assay

Direct infusion of mefloquine into nucleus accumbens coupled to stress is anxiogenic. (a) Stressed mice that received direct infusion of mefloquine into nucleus accumbens trend towards less time in the open arms ( t p=0.13, Student’s t-test, n =
Figure Legend Snippet: Direct infusion of mefloquine into nucleus accumbens coupled to stress is anxiogenic. (a) Stressed mice that received direct infusion of mefloquine into nucleus accumbens trend towards less time in the open arms ( t p=0.13, Student’s t-test, n =

Techniques Used: Mouse Assay

22) Product Images from "Comparison between Flow Cytometry, Microscopy, and Lactate Dehydrogenase-Based Enzyme-Linked Immunosorbent Assay for Plasmodium falciparum Drug Susceptibility Testing under Field Conditions"

Article Title: Comparison between Flow Cytometry, Microscopy, and Lactate Dehydrogenase-Based Enzyme-Linked Immunosorbent Assay for Plasmodium falciparum Drug Susceptibility Testing under Field Conditions

Journal: Journal of Clinical Microbiology

doi: 10.1128/JCM.01226-15

(A) An example of paradoxical increase in signal with very high concentrations of mefloquine. (B) Paradoxical increased apparent growth at high drug concentrations for the seven drugs with flow cytometry (FCM) and DELI methods (see Materials and Methods for the definition and calculation of paradoxical growth).
Figure Legend Snippet: (A) An example of paradoxical increase in signal with very high concentrations of mefloquine. (B) Paradoxical increased apparent growth at high drug concentrations for the seven drugs with flow cytometry (FCM) and DELI methods (see Materials and Methods for the definition and calculation of paradoxical growth).

Techniques Used: Flow Cytometry, Cytometry

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    Millipore mefloquine hydrochloride
    Pharmacological characterization of MoNNet neuronal and network activity. a Characterization of MoNNet functional properties by pharmacological treatments with GABAergic and Glutamatergic synaptic inhibitors: Bicuculine [10 μM], Picrotoxin[10 μM], D-APV [40 μM] and NBQX [10 μM]), and ionic channel blockers: <t>Mefloquine</t> [25 μM], Nifedipine [10 μM] and TTX [1 μM]. Control samples were treated with the solvent DMSO alone. Y -axes quantify the increment relative to the baseline in same samples, after 1 h of treatments. Number of biological replicates ( n ) is shown on the plot. Blue and Orange bars are for MoNNets in phase I and II, respectively. Statistical significance was calculated by using one-way ANOVA and Dunnett multiple comparison test. * padj
    Mefloquine Hydrochloride, supplied by Millipore, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/mefloquine hydrochloride/product/Millipore
    Average 86 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    mefloquine hydrochloride - by Bioz Stars, 2022-12
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    86
    Millipore mefloquine
    Pharmacological characterization of MoNNet neuronal and network activity. a Characterization of MoNNet functional properties by pharmacological treatments with GABAergic and Glutamatergic synaptic inhibitors: Bicuculine [10 μM], Picrotoxin[10 μM], D-APV [40 μM] and NBQX [10 μM]), and ionic channel blockers: <t>Mefloquine</t> [25 μM], Nifedipine [10 μM] and TTX [1 μM]. Control samples were treated with the solvent DMSO alone. Y -axes quantify the increment relative to the baseline in same samples, after 1 h of treatments. Number of biological replicates ( n ) is shown on the plot. Blue and Orange bars are for MoNNets in phase I and II, respectively. Statistical significance was calculated by using one-way ANOVA and Dunnett multiple comparison test. * padj
    Mefloquine, supplied by Millipore, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/mefloquine/product/Millipore
    Average 86 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    mefloquine - by Bioz Stars, 2022-12
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    Pharmacological characterization of MoNNet neuronal and network activity. a Characterization of MoNNet functional properties by pharmacological treatments with GABAergic and Glutamatergic synaptic inhibitors: Bicuculine [10 μM], Picrotoxin[10 μM], D-APV [40 μM] and NBQX [10 μM]), and ionic channel blockers: Mefloquine [25 μM], Nifedipine [10 μM] and TTX [1 μM]. Control samples were treated with the solvent DMSO alone. Y -axes quantify the increment relative to the baseline in same samples, after 1 h of treatments. Number of biological replicates ( n ) is shown on the plot. Blue and Orange bars are for MoNNets in phase I and II, respectively. Statistical significance was calculated by using one-way ANOVA and Dunnett multiple comparison test. * padj

    Journal: Nature Communications

    Article Title: An in vitro model of neuronal ensembles

    doi: 10.1038/s41467-022-31073-1

    Figure Lengend Snippet: Pharmacological characterization of MoNNet neuronal and network activity. a Characterization of MoNNet functional properties by pharmacological treatments with GABAergic and Glutamatergic synaptic inhibitors: Bicuculine [10 μM], Picrotoxin[10 μM], D-APV [40 μM] and NBQX [10 μM]), and ionic channel blockers: Mefloquine [25 μM], Nifedipine [10 μM] and TTX [1 μM]. Control samples were treated with the solvent DMSO alone. Y -axes quantify the increment relative to the baseline in same samples, after 1 h of treatments. Number of biological replicates ( n ) is shown on the plot. Blue and Orange bars are for MoNNets in phase I and II, respectively. Statistical significance was calculated by using one-way ANOVA and Dunnett multiple comparison test. * padj

    Article Snippet: Synaptic and ion channel inhibition experiments were performed with bicuculline (10 μM, Cat# 14340, Sigma), picrotoxin (10 μM, Cat# P1675, Sigma), NBQX (10 μM, Cat# N183, Sigma), D-APV (40 μM, Cat# A8054, Sigma), Nifedipine (10 μM, Cat# N7634, Sigma), TTX (1 μM, Cat# 1078, Tocris) and Mefloquine (25 μM, Cat# M2319, Sigma).

    Techniques: Activity Assay, Functional Assay