Journal:

Article Title: Production of Protective Human Antipneumococcal Antibodies by Transgenic Mice with Human Immunoglobulin Loci

doi:

Figure Lengend Snippet: Survival of CBA/N mice after infection with serotype 3 S. pneumoniae. (A) Survival of mice treated with MAb doses of 10 μg; (B) survival of mice treated with mAb doses of 1 μg. The y axes show percentages of mice surviving the number of days after infection depicted on the x axes. Mice were infected as described in the text after the administration of IgM (depicted by ×), PBS (#), MAb 1.2 (■), or mAb 1.10 (○). The experiments were performed twice, and the results of one experiment are shown. In panel A, IgM (x) and PBS (#) had identical survival.

Article Snippet: Mouse inoculations were performed as follows: groups of 10 mice each received 0.5 ml (1 or 10 μg in sterile saline) of MAb 1.2, MAb 1.10, the human myeloma IgM control (Calbiochem) used as an isotype control as described elsewhere ( 46 ), or PBS intraperitoneally; 1 h later, 0.2 ml (300 CFU in tryptic soy broth) of S. pneumoniae (ATCC strain 10813) was given via intravenous inoculation into the lateral tail vein.

Techniques: Infection

Journal:

Article Title: In Vivo Pharmacodynamics of a New Oxazolidinone (Linezolid)

doi: 10.1128/AAC.46.11.3484-3489.2002

Figure Lengend Snippet: In vitro susceptibility of linezolid against susceptible and resistant S. pneumoniae and S. aureus strains

Article Snippet: The relationships between microbiologic effect against S. pneumoniae ATCC 10813 and each of the pharmacodynamic parameters, i.e., the percent time above the MIC, the AUC/MIC, and the peak/MIC, are shown in Fig. .

Techniques: In Vitro

Journal:

Article Title: In Vivo Pharmacodynamics of a New Oxazolidinone (Linezolid)

doi: 10.1128/AAC.46.11.3484-3489.2002

Figure Lengend Snippet: (A) In vivo PAE of linezolid after administration of single doses of 20 and 80 mg/kg against S. pneumoniae ATCC 10813. Symbols: □, data obtained with the 20-mg/kg dose; ▵, data obtained with the 80-mg/kg dose. Each symbol represents the mean ± the standard deviation for two mice. The solid bars represent the time that free-drug levels remained above the MIC. The open bars represent the time that total drug levels remained above the MIC. (B) In vivo PAE of linezolid after administration of single doses of 20 and 80 mg/kg against S. aureus ATCC 6538p. Symbols: □, data obtained with the 20-mg/kg dose; ▵, data obtained with the 80-mg/kg dose. Each symbol represents the mean ± the standard deviation for two mice. The solid bars represent the time that free-drug levels remained above the MIC. The open bars represent the time that total drug levels remained above the MIC.

Article Snippet: The relationships between microbiologic effect against S. pneumoniae ATCC 10813 and each of the pharmacodynamic parameters, i.e., the percent time above the MIC, the AUC/MIC, and the peak/MIC, are shown in Fig. .

Techniques: In Vivo, Standard Deviation

Journal:

Article Title: In Vivo Pharmacodynamics of a New Oxazolidinone (Linezolid)

doi: 10.1128/AAC.46.11.3484-3489.2002

Figure Lengend Snippet: Relationships between the percentage of the dosing interval that levels in serum remained above the MIC for S. pneumoniae ATCC 10813, the 24-h AUC/MIC, and the peak/MIC and the log10 number of CFU/thigh after 24 h of therapy. Each symbol represents the data for two mice. The lines represent the best fit line. R2 is the coefficient of determination.

Article Snippet: The relationships between microbiologic effect against S. pneumoniae ATCC 10813 and each of the pharmacodynamic parameters, i.e., the percent time above the MIC, the AUC/MIC, and the peak/MIC, are shown in Fig. .

Techniques:

Journal:

Article Title: In Vivo Pharmacodynamics of a New Oxazolidinone (Linezolid)

doi: 10.1128/AAC.46.11.3484-3489.2002

Figure Lengend Snippet: Relationship between between the percentage of the dosing interval that both total and free-drug levels in serum remained above the MIC for S. pneumoniae ATCC 10813. Each symbol represents the data for two mice. The lines represent the best fit line. R2 is the coefficient of determination.

Article Snippet: The relationships between microbiologic effect against S. pneumoniae ATCC 10813 and each of the pharmacodynamic parameters, i.e., the percent time above the MIC, the AUC/MIC, and the peak/MIC, are shown in Fig. .

Techniques:

Journal:

Article Title: In Vivo Pharmacodynamics of a New Oxazolidinone (Linezolid)

doi: 10.1128/AAC.46.11.3484-3489.2002

Figure Lengend Snippet: Bacteriostatic doses for linezolid against S. pneumoniae and S. aureus

Article Snippet: The relationships between microbiologic effect against S. pneumoniae ATCC 10813 and each of the pharmacodynamic parameters, i.e., the percent time above the MIC, the AUC/MIC, and the peak/MIC, are shown in Fig. .

Techniques:

Journal:

Article Title: In Vivo Pharmacodynamic Activity of Daptomycin

doi: 10.1128/AAC.48.1.63-68.2004

Figure Lengend Snippet: In vivo PAE of daptomycin against S. pneumoniae ATCC 10813 after administration of single doses of 2.5 (triangles) and 10 (squares) mg/kg. T > MIC, time that the concentration remains above the MIC.

Article Snippet: The low values for E. faecium may reflect the poor growth of the two strains of E. faecium in control mice (0.34 and 0.37 log 10 CFU/thigh over 24 h). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 4. caption a7 Dose-response curves for daptomycin against various strains of S. pneumoniae . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 5. caption a7 Dose-response curves for daptomycin against various strains of S. aureus (circles) and E. faecium (squares). table ft1 table-wrap mode="anchored" t5 TABLE 3. caption a7 Organism MIC (mg/liter) Static dose (mg/kg/24 h) a 24-h AUC/MIC ratio Peak/MIC ratio Static dose 1 log killing 2 log killing Static dose 1 log killing 2 log killing S. pneumoniae ATCC 10813 0.12 2.16 168 390 582 25.1 48.2 86.5 S. pneumoniae CDC 145 0.12 0.954 74.7 108 157 11.8 16 23.4 S. pneumoniae CDC 1199 0.12 2.62 203 346 594 30.5 51.5 88.1 S. pneumoniae CDC 1396 0.12 1.5 117 150 190 17.4 22.3 28.3 S. pneumoniae CDC 673 0.12 3.05 237 467 815 35.5 69.5 121 S. pneumoniae CDC 1325 0.25 5.34 199 373 673 29.8 55.5 100 S. pneumoniae CDC 49619 0.25 4.9 182 337 703 27.3 50 104 S. pneumoniae CDC 1020 0.25 3.39 126 215 395 18.9 32 58.5 Mean ± SD (95% CI) for S. pneumoniae 160 ± 51 (72-316) 290 ± 121 (100-660) 498 ± 131 (117-813) 24 ± 7.6 (11-44) 42.1 ± 17.2 (15-98) 73.9 ± 34.2 (20-204) S. aureus ATCC 25923 0.5 20.8 388 594 896 59 109 197 S. aureus ATCC 33591 0.5 28.6 537 733 1,099 93.6 147 264 S. aureus ATCC 29213 0.5 22.5 420 588 788 66.2 107 163 S. aureus ATCC 6538p 0.5 21.9 409 750 1,460 63.6 152 398 Mean ± SD (95% CI) for S. aureus 438 ± 67 (316-550) 666 ± 87 (501-832) 1,061 ± 296 (603-1,738) 70.6 ± 15.6 (47-102) 129 ± 24.1 (86-184) 255 ± 104 (114-507) E. faecium VA 20 2 0.203 0.94 4.14 ND b 0.14 0.62 ND E. faecium VA 21 2 0.36 1.67 33.8 ND 0.25 5.05 ND Open in a separate window a Calculations are based on total drug levels.

Techniques: In Vivo, Concentration Assay

Journal:

Article Title: In Vivo Pharmacodynamic Activity of Daptomycin

doi: 10.1128/AAC.48.1.63-68.2004

Figure Lengend Snippet: In vivo PAEs of free and total daptomycin concentrations of against S. aureus and S. pneumoniae

Article Snippet: The low values for E. faecium may reflect the poor growth of the two strains of E. faecium in control mice (0.34 and 0.37 log 10 CFU/thigh over 24 h). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 4. caption a7 Dose-response curves for daptomycin against various strains of S. pneumoniae . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 5. caption a7 Dose-response curves for daptomycin against various strains of S. aureus (circles) and E. faecium (squares). table ft1 table-wrap mode="anchored" t5 TABLE 3. caption a7 Organism MIC (mg/liter) Static dose (mg/kg/24 h) a 24-h AUC/MIC ratio Peak/MIC ratio Static dose 1 log killing 2 log killing Static dose 1 log killing 2 log killing S. pneumoniae ATCC 10813 0.12 2.16 168 390 582 25.1 48.2 86.5 S. pneumoniae CDC 145 0.12 0.954 74.7 108 157 11.8 16 23.4 S. pneumoniae CDC 1199 0.12 2.62 203 346 594 30.5 51.5 88.1 S. pneumoniae CDC 1396 0.12 1.5 117 150 190 17.4 22.3 28.3 S. pneumoniae CDC 673 0.12 3.05 237 467 815 35.5 69.5 121 S. pneumoniae CDC 1325 0.25 5.34 199 373 673 29.8 55.5 100 S. pneumoniae CDC 49619 0.25 4.9 182 337 703 27.3 50 104 S. pneumoniae CDC 1020 0.25 3.39 126 215 395 18.9 32 58.5 Mean ± SD (95% CI) for S. pneumoniae 160 ± 51 (72-316) 290 ± 121 (100-660) 498 ± 131 (117-813) 24 ± 7.6 (11-44) 42.1 ± 17.2 (15-98) 73.9 ± 34.2 (20-204) S. aureus ATCC 25923 0.5 20.8 388 594 896 59 109 197 S. aureus ATCC 33591 0.5 28.6 537 733 1,099 93.6 147 264 S. aureus ATCC 29213 0.5 22.5 420 588 788 66.2 107 163 S. aureus ATCC 6538p 0.5 21.9 409 750 1,460 63.6 152 398 Mean ± SD (95% CI) for S. aureus 438 ± 67 (316-550) 666 ± 87 (501-832) 1,061 ± 296 (603-1,738) 70.6 ± 15.6 (47-102) 129 ± 24.1 (86-184) 255 ± 104 (114-507) E. faecium VA 20 2 0.203 0.94 4.14 ND b 0.14 0.62 ND E. faecium VA 21 2 0.36 1.67 33.8 ND 0.25 5.05 ND Open in a separate window a Calculations are based on total drug levels.

Techniques: In Vivo

Journal:

Article Title: In Vivo Pharmacodynamic Activity of Daptomycin

doi: 10.1128/AAC.48.1.63-68.2004

Figure Lengend Snippet: Static doses of daptomycin for different dosing intervals

Article Snippet: The low values for E. faecium may reflect the poor growth of the two strains of E. faecium in control mice (0.34 and 0.37 log 10 CFU/thigh over 24 h). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 4. caption a7 Dose-response curves for daptomycin against various strains of S. pneumoniae . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 5. caption a7 Dose-response curves for daptomycin against various strains of S. aureus (circles) and E. faecium (squares). table ft1 table-wrap mode="anchored" t5 TABLE 3. caption a7 Organism MIC (mg/liter) Static dose (mg/kg/24 h) a 24-h AUC/MIC ratio Peak/MIC ratio Static dose 1 log killing 2 log killing Static dose 1 log killing 2 log killing S. pneumoniae ATCC 10813 0.12 2.16 168 390 582 25.1 48.2 86.5 S. pneumoniae CDC 145 0.12 0.954 74.7 108 157 11.8 16 23.4 S. pneumoniae CDC 1199 0.12 2.62 203 346 594 30.5 51.5 88.1 S. pneumoniae CDC 1396 0.12 1.5 117 150 190 17.4 22.3 28.3 S. pneumoniae CDC 673 0.12 3.05 237 467 815 35.5 69.5 121 S. pneumoniae CDC 1325 0.25 5.34 199 373 673 29.8 55.5 100 S. pneumoniae CDC 49619 0.25 4.9 182 337 703 27.3 50 104 S. pneumoniae CDC 1020 0.25 3.39 126 215 395 18.9 32 58.5 Mean ± SD (95% CI) for S. pneumoniae 160 ± 51 (72-316) 290 ± 121 (100-660) 498 ± 131 (117-813) 24 ± 7.6 (11-44) 42.1 ± 17.2 (15-98) 73.9 ± 34.2 (20-204) S. aureus ATCC 25923 0.5 20.8 388 594 896 59 109 197 S. aureus ATCC 33591 0.5 28.6 537 733 1,099 93.6 147 264 S. aureus ATCC 29213 0.5 22.5 420 588 788 66.2 107 163 S. aureus ATCC 6538p 0.5 21.9 409 750 1,460 63.6 152 398 Mean ± SD (95% CI) for S. aureus 438 ± 67 (316-550) 666 ± 87 (501-832) 1,061 ± 296 (603-1,738) 70.6 ± 15.6 (47-102) 129 ± 24.1 (86-184) 255 ± 104 (114-507) E. faecium VA 20 2 0.203 0.94 4.14 ND b 0.14 0.62 ND E. faecium VA 21 2 0.36 1.67 33.8 ND 0.25 5.05 ND Open in a separate window a Calculations are based on total drug levels.

Techniques:

Journal:

Article Title: In Vivo Pharmacodynamic Activity of Daptomycin

doi: 10.1128/AAC.48.1.63-68.2004

Figure Lengend Snippet: Dose-response curves for daptomycin against various strains of S. pneumoniae.

Article Snippet: The low values for E. faecium may reflect the poor growth of the two strains of E. faecium in control mice (0.34 and 0.37 log 10 CFU/thigh over 24 h). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 4. caption a7 Dose-response curves for daptomycin against various strains of S. pneumoniae . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 5. caption a7 Dose-response curves for daptomycin against various strains of S. aureus (circles) and E. faecium (squares). table ft1 table-wrap mode="anchored" t5 TABLE 3. caption a7 Organism MIC (mg/liter) Static dose (mg/kg/24 h) a 24-h AUC/MIC ratio Peak/MIC ratio Static dose 1 log killing 2 log killing Static dose 1 log killing 2 log killing S. pneumoniae ATCC 10813 0.12 2.16 168 390 582 25.1 48.2 86.5 S. pneumoniae CDC 145 0.12 0.954 74.7 108 157 11.8 16 23.4 S. pneumoniae CDC 1199 0.12 2.62 203 346 594 30.5 51.5 88.1 S. pneumoniae CDC 1396 0.12 1.5 117 150 190 17.4 22.3 28.3 S. pneumoniae CDC 673 0.12 3.05 237 467 815 35.5 69.5 121 S. pneumoniae CDC 1325 0.25 5.34 199 373 673 29.8 55.5 100 S. pneumoniae CDC 49619 0.25 4.9 182 337 703 27.3 50 104 S. pneumoniae CDC 1020 0.25 3.39 126 215 395 18.9 32 58.5 Mean ± SD (95% CI) for S. pneumoniae 160 ± 51 (72-316) 290 ± 121 (100-660) 498 ± 131 (117-813) 24 ± 7.6 (11-44) 42.1 ± 17.2 (15-98) 73.9 ± 34.2 (20-204) S. aureus ATCC 25923 0.5 20.8 388 594 896 59 109 197 S. aureus ATCC 33591 0.5 28.6 537 733 1,099 93.6 147 264 S. aureus ATCC 29213 0.5 22.5 420 588 788 66.2 107 163 S. aureus ATCC 6538p 0.5 21.9 409 750 1,460 63.6 152 398 Mean ± SD (95% CI) for S. aureus 438 ± 67 (316-550) 666 ± 87 (501-832) 1,061 ± 296 (603-1,738) 70.6 ± 15.6 (47-102) 129 ± 24.1 (86-184) 255 ± 104 (114-507) E. faecium VA 20 2 0.203 0.94 4.14 ND b 0.14 0.62 ND E. faecium VA 21 2 0.36 1.67 33.8 ND 0.25 5.05 ND Open in a separate window a Calculations are based on total drug levels.

Techniques:

Journal:

Article Title: In Vivo Pharmacodynamic Activity of Daptomycin

doi: 10.1128/AAC.48.1.63-68.2004

Figure Lengend Snippet: MICs, static doses, and magnitudes of 24-h AUC/MIC and peak/MIC ratios required to produce a bacteriostatic effect and killing of 1 and 2 log 10 CFU per thigh over 24 h

Article Snippet: The low values for E. faecium may reflect the poor growth of the two strains of E. faecium in control mice (0.34 and 0.37 log 10 CFU/thigh over 24 h). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 4. caption a7 Dose-response curves for daptomycin against various strains of S. pneumoniae . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 5. caption a7 Dose-response curves for daptomycin against various strains of S. aureus (circles) and E. faecium (squares). table ft1 table-wrap mode="anchored" t5 TABLE 3. caption a7 Organism MIC (mg/liter) Static dose (mg/kg/24 h) a 24-h AUC/MIC ratio Peak/MIC ratio Static dose 1 log killing 2 log killing Static dose 1 log killing 2 log killing S. pneumoniae ATCC 10813 0.12 2.16 168 390 582 25.1 48.2 86.5 S. pneumoniae CDC 145 0.12 0.954 74.7 108 157 11.8 16 23.4 S. pneumoniae CDC 1199 0.12 2.62 203 346 594 30.5 51.5 88.1 S. pneumoniae CDC 1396 0.12 1.5 117 150 190 17.4 22.3 28.3 S. pneumoniae CDC 673 0.12 3.05 237 467 815 35.5 69.5 121 S. pneumoniae CDC 1325 0.25 5.34 199 373 673 29.8 55.5 100 S. pneumoniae CDC 49619 0.25 4.9 182 337 703 27.3 50 104 S. pneumoniae CDC 1020 0.25 3.39 126 215 395 18.9 32 58.5 Mean ± SD (95% CI) for S. pneumoniae 160 ± 51 (72-316) 290 ± 121 (100-660) 498 ± 131 (117-813) 24 ± 7.6 (11-44) 42.1 ± 17.2 (15-98) 73.9 ± 34.2 (20-204) S. aureus ATCC 25923 0.5 20.8 388 594 896 59 109 197 S. aureus ATCC 33591 0.5 28.6 537 733 1,099 93.6 147 264 S. aureus ATCC 29213 0.5 22.5 420 588 788 66.2 107 163 S. aureus ATCC 6538p 0.5 21.9 409 750 1,460 63.6 152 398 Mean ± SD (95% CI) for S. aureus 438 ± 67 (316-550) 666 ± 87 (501-832) 1,061 ± 296 (603-1,738) 70.6 ± 15.6 (47-102) 129 ± 24.1 (86-184) 255 ± 104 (114-507) E. faecium VA 20 2 0.203 0.94 4.14 ND b 0.14 0.62 ND E. faecium VA 21 2 0.36 1.67 33.8 ND 0.25 5.05 ND Open in a separate window a Calculations are based on total drug levels.

Techniques:

Journal:

Article Title: In Vivo Pharmacodynamic Activity of Daptomycin

doi: 10.1128/AAC.48.1.63-68.2004

Figure Lengend Snippet: AUC over 24 h for free daptomycin associated with the static dose and doses producing killing of 1 and 2 log10 CFU/thigh for multiple strains of S. pneumoniae and S. aureus.

Article Snippet: The low values for E. faecium may reflect the poor growth of the two strains of E. faecium in control mice (0.34 and 0.37 log 10 CFU/thigh over 24 h). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 4. caption a7 Dose-response curves for daptomycin against various strains of S. pneumoniae . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 5. caption a7 Dose-response curves for daptomycin against various strains of S. aureus (circles) and E. faecium (squares). table ft1 table-wrap mode="anchored" t5 TABLE 3. caption a7 Organism MIC (mg/liter) Static dose (mg/kg/24 h) a 24-h AUC/MIC ratio Peak/MIC ratio Static dose 1 log killing 2 log killing Static dose 1 log killing 2 log killing S. pneumoniae ATCC 10813 0.12 2.16 168 390 582 25.1 48.2 86.5 S. pneumoniae CDC 145 0.12 0.954 74.7 108 157 11.8 16 23.4 S. pneumoniae CDC 1199 0.12 2.62 203 346 594 30.5 51.5 88.1 S. pneumoniae CDC 1396 0.12 1.5 117 150 190 17.4 22.3 28.3 S. pneumoniae CDC 673 0.12 3.05 237 467 815 35.5 69.5 121 S. pneumoniae CDC 1325 0.25 5.34 199 373 673 29.8 55.5 100 S. pneumoniae CDC 49619 0.25 4.9 182 337 703 27.3 50 104 S. pneumoniae CDC 1020 0.25 3.39 126 215 395 18.9 32 58.5 Mean ± SD (95% CI) for S. pneumoniae 160 ± 51 (72-316) 290 ± 121 (100-660) 498 ± 131 (117-813) 24 ± 7.6 (11-44) 42.1 ± 17.2 (15-98) 73.9 ± 34.2 (20-204) S. aureus ATCC 25923 0.5 20.8 388 594 896 59 109 197 S. aureus ATCC 33591 0.5 28.6 537 733 1,099 93.6 147 264 S. aureus ATCC 29213 0.5 22.5 420 588 788 66.2 107 163 S. aureus ATCC 6538p 0.5 21.9 409 750 1,460 63.6 152 398 Mean ± SD (95% CI) for S. aureus 438 ± 67 (316-550) 666 ± 87 (501-832) 1,061 ± 296 (603-1,738) 70.6 ± 15.6 (47-102) 129 ± 24.1 (86-184) 255 ± 104 (114-507) E. faecium VA 20 2 0.203 0.94 4.14 ND b 0.14 0.62 ND E. faecium VA 21 2 0.36 1.67 33.8 ND 0.25 5.05 ND Open in a separate window a Calculations are based on total drug levels.

Techniques:

Journal: The ISME Journal

Article Title: Taeniasis impacts human gut microbiome composition and function

doi: 10.1093/ismejo/wrae213

Figure Lengend Snippet: Microbial metabolomic pathway analysis and in vitro experiments. (A) The in vitro culture of B. longum or E. coli in the presence of excretory-secretory protein (ESP) (5 mg/ml) collected from different T. saginata tapeworm isolates ( n = 3 or 4). Colony-forming units (CFUs) were counted on plates ( n = 2 technical replicates for each sample). (B) PCoA using Bray–Curtis distance based on the relative abundances of MetaCyC pathways. (C) The pathways that were significantly increased in infection and negatively correlated with Bifidobacterium. The absolute value of the coefficient correlation between each pathway and the abundance of Bifidobacterium ( X -axis) and the coefficient in MaAsLin2 analysis (Y-axis) are shown. Only pathways with q value <0.05 in MaAsLin2 analysis were indicated with names. (D) The species with significantly differential abundance in the stachyose degradation pathway (the prevalence >0.1 and q value <0.25 after FDR correction) in MaAsLin2 analysis. The error bars indicate the 95% confidence intervals of coefficient estimates. (E) The negative correlations between B. longum and other species in the stachyose degradation pathway. The relative abundance was normalized by the centered log-ratio method. (F) In vitro growth rate of B. longum (left) and D. longicatena (right) in the presence of different concentrations (w/v) of stachyose ( n = 3 replicates for each sample). (G) In vitro growth experiments of B. longum (left) and D. longicatena (right) in the presence of different concentrations (w/v) of ESP ( n = 3 or 4 replicates). The data for panels A, F, and G are shown for mean ± SD, and P values for panels A and G were calculated by Student’s t -test. The R 2 statistic and P value for panel B were calculated by permutational multivariate analysis of variance (PERMANOVA). The box plot in panel B represents the 25th percentile, median, and 75th percentile and whiskers stretch to 1.5 times the interquartile range from the corresponding hinge.

Article Snippet: The Dorea longicatena strain (DSM13814, DSMZ, German), B. longum strain (ATCC15707, Mingzhoubio, China), and Escherichia coli O157:H7 strain (ATCC700728, Biobw, China) were purchased from bioresource centers and cultured in modified PYG medium (DSMZ), GAM medium (Cat. HB8518, HopeBio, China), and LB medium at 37°C in anaerobic condition, respectively.

Techniques: In Vitro, Infection

Journal:

Article Title: In Vivo Pharmacodynamic Activities of Two Glycylcyclines (GAR-936 and WAY 152,288) against Various Gram-Positive and Gram-Negative Bacteria

doi:

Figure Lengend Snippet: Organisms used and in vitro susceptibilities to GAR-936, WAY 152,288, and minocycline

Article Snippet: The MBCs were usually 1 to 2 dilutions higher than the MICs except for those for K. pneumoniae ATCC 43816 and E. coli 894. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism GAR-936 WAY 152,288 Minocycline MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) S. pneumoniae ATCC 10813 0.12 0.25 0.12 0.25 0.25 0.5 S. pneumoniae ATCC 49619 0.06 0.06 0.03 0.03 0.06 0.06 S. pneumoniae 1199 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1020 0.06 0.12 0.06 0.12 4 8 S. pneumoniae 1293 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1396 0.12 0.5 0.12 0.12 4 4 S. aureus ATCC 25923 0.12 0.5 0.25 0.5 0.12 ≥0.5 S. aureus ATCC 33591 0.5 1 1 1 8 8 S. aureus ATCC 29213 0.25 0.5 0.12 0.5 0.06 ≥0.25 S. aureus WIS-2 0.25 1 0.25 1 0.06 ≥0.25 E. coli ATCC 25922 0.12 0.12 0.12 0.25 0.25 0.25 E. coli 894 0.12 >8 0.25 >8 8 8 K. pneumoniae ATCC 43816 0.5 >32 0.5 >32 4 32 Open in a separate window Organisms used and in vitro susceptibilities to GAR-936, WAY 152,288, and minocycline

Techniques: In Vitro

Journal:

Article Title: In Vivo Pharmacodynamic Activities of Two Glycylcyclines (GAR-936 and WAY 152,288) against Various Gram-Positive and Gram-Negative Bacteria

doi:

Figure Lengend Snippet: Pharmacokinetic properties of the glycylcyclines in neutropenic mice infected with S. pneumoniae ATCC 10813

Article Snippet: The MBCs were usually 1 to 2 dilutions higher than the MICs except for those for K. pneumoniae ATCC 43816 and E. coli 894. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism GAR-936 WAY 152,288 Minocycline MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) S. pneumoniae ATCC 10813 0.12 0.25 0.12 0.25 0.25 0.5 S. pneumoniae ATCC 49619 0.06 0.06 0.03 0.03 0.06 0.06 S. pneumoniae 1199 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1020 0.06 0.12 0.06 0.12 4 8 S. pneumoniae 1293 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1396 0.12 0.5 0.12 0.12 4 4 S. aureus ATCC 25923 0.12 0.5 0.25 0.5 0.12 ≥0.5 S. aureus ATCC 33591 0.5 1 1 1 8 8 S. aureus ATCC 29213 0.25 0.5 0.12 0.5 0.06 ≥0.25 S. aureus WIS-2 0.25 1 0.25 1 0.06 ≥0.25 E. coli ATCC 25922 0.12 0.12 0.12 0.25 0.25 0.25 E. coli 894 0.12 >8 0.25 >8 8 8 K. pneumoniae ATCC 43816 0.5 >32 0.5 >32 4 32 Open in a separate window Organisms used and in vitro susceptibilities to GAR-936, WAY 152,288, and minocycline

Techniques: Infection

Journal:

Article Title: In Vivo Pharmacodynamic Activities of Two Glycylcyclines (GAR-936 and WAY 152,288) against Various Gram-Positive and Gram-Negative Bacteria

doi:

Figure Lengend Snippet: Effects of various GAR-936 (a), WAY 152,288 (b), and minocycline (c) dosage regimens on the number of S. pneumoniae ATCC 10813 organisms in the neutropenic mouse thigh muscle infection model after 48 h of treatment. The dashed horizontal line represents the number of CFU per thigh at the start of treatment. ●, single dose; ○, once-daily dose; ▾, twice-daily dose; ▿, four-times-daily dose; ——, single dose; ······, once-daily dose; –––, twice-daily dose; —··, four-times-daily dose; —–, log CFU at start of treatment.

Article Snippet: The MBCs were usually 1 to 2 dilutions higher than the MICs except for those for K. pneumoniae ATCC 43816 and E. coli 894. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism GAR-936 WAY 152,288 Minocycline MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) S. pneumoniae ATCC 10813 0.12 0.25 0.12 0.25 0.25 0.5 S. pneumoniae ATCC 49619 0.06 0.06 0.03 0.03 0.06 0.06 S. pneumoniae 1199 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1020 0.06 0.12 0.06 0.12 4 8 S. pneumoniae 1293 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1396 0.12 0.5 0.12 0.12 4 4 S. aureus ATCC 25923 0.12 0.5 0.25 0.5 0.12 ≥0.5 S. aureus ATCC 33591 0.5 1 1 1 8 8 S. aureus ATCC 29213 0.25 0.5 0.12 0.5 0.06 ≥0.25 S. aureus WIS-2 0.25 1 0.25 1 0.06 ≥0.25 E. coli ATCC 25922 0.12 0.12 0.12 0.25 0.25 0.25 E. coli 894 0.12 >8 0.25 >8 8 8 K. pneumoniae ATCC 43816 0.5 >32 0.5 >32 4 32 Open in a separate window Organisms used and in vitro susceptibilities to GAR-936, WAY 152,288, and minocycline

Techniques: Infection

Journal:

Article Title: In Vivo Pharmacodynamic Activities of Two Glycylcyclines (GAR-936 and WAY 152,288) against Various Gram-Positive and Gram-Negative Bacteria

doi:

Figure Lengend Snippet: Dose-effect relationship of the glycylcyclines GAR-936 (a) and WAY 152,288 (b) in an experimental thigh muscle infection with S. pneumoniae 1199 in neutropenic mice. Each point represents the results for a single mouse. The sigmoid curve represents the dose-effect curve established according to the Hill equation.

Article Snippet: The MBCs were usually 1 to 2 dilutions higher than the MICs except for those for K. pneumoniae ATCC 43816 and E. coli 894. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism GAR-936 WAY 152,288 Minocycline MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) S. pneumoniae ATCC 10813 0.12 0.25 0.12 0.25 0.25 0.5 S. pneumoniae ATCC 49619 0.06 0.06 0.03 0.03 0.06 0.06 S. pneumoniae 1199 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1020 0.06 0.12 0.06 0.12 4 8 S. pneumoniae 1293 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1396 0.12 0.5 0.12 0.12 4 4 S. aureus ATCC 25923 0.12 0.5 0.25 0.5 0.12 ≥0.5 S. aureus ATCC 33591 0.5 1 1 1 8 8 S. aureus ATCC 29213 0.25 0.5 0.12 0.5 0.06 ≥0.25 S. aureus WIS-2 0.25 1 0.25 1 0.06 ≥0.25 E. coli ATCC 25922 0.12 0.12 0.12 0.25 0.25 0.25 E. coli 894 0.12 >8 0.25 >8 8 8 K. pneumoniae ATCC 43816 0.5 >32 0.5 >32 4 32 Open in a separate window Organisms used and in vitro susceptibilities to GAR-936, WAY 152,288, and minocycline

Techniques: Infection

Journal:

Article Title: In Vivo Pharmacodynamic Activities of Two Glycylcyclines (GAR-936 and WAY 152,288) against Various Gram-Positive and Gram-Negative Bacteria

doi:

Figure Lengend Snippet: Dose-effect relationship of the glycylcyclines against various organisms, using a twice-daily dosing regimen

Article Snippet: The MBCs were usually 1 to 2 dilutions higher than the MICs except for those for K. pneumoniae ATCC 43816 and E. coli 894. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism GAR-936 WAY 152,288 Minocycline MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) S. pneumoniae ATCC 10813 0.12 0.25 0.12 0.25 0.25 0.5 S. pneumoniae ATCC 49619 0.06 0.06 0.03 0.03 0.06 0.06 S. pneumoniae 1199 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1020 0.06 0.12 0.06 0.12 4 8 S. pneumoniae 1293 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1396 0.12 0.5 0.12 0.12 4 4 S. aureus ATCC 25923 0.12 0.5 0.25 0.5 0.12 ≥0.5 S. aureus ATCC 33591 0.5 1 1 1 8 8 S. aureus ATCC 29213 0.25 0.5 0.12 0.5 0.06 ≥0.25 S. aureus WIS-2 0.25 1 0.25 1 0.06 ≥0.25 E. coli ATCC 25922 0.12 0.12 0.12 0.25 0.25 0.25 E. coli 894 0.12 >8 0.25 >8 8 8 K. pneumoniae ATCC 43816 0.5 >32 0.5 >32 4 32 Open in a separate window Organisms used and in vitro susceptibilities to GAR-936, WAY 152,288, and minocycline

Techniques:

Journal:

Article Title: In Vivo Pharmacodynamic Activities of Two Glycylcyclines (GAR-936 and WAY 152,288) against Various Gram-Positive and Gram-Negative Bacteria

doi:

Figure Lengend Snippet: In vivo PAE of GAR-936 after administration of 3 mg/kg subcutaneously to neutropenic mice infected with S. pneumoniae ATCC 10813 (a) and E. coli ATCC 25922 (b). t>MIC, period when an active concentration of GAR-936 is present; ●, untreated mice; ○, GAR-936-treated mice.

Article Snippet: The MBCs were usually 1 to 2 dilutions higher than the MICs except for those for K. pneumoniae ATCC 43816 and E. coli 894. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism GAR-936 WAY 152,288 Minocycline MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) S. pneumoniae ATCC 10813 0.12 0.25 0.12 0.25 0.25 0.5 S. pneumoniae ATCC 49619 0.06 0.06 0.03 0.03 0.06 0.06 S. pneumoniae 1199 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1020 0.06 0.12 0.06 0.12 4 8 S. pneumoniae 1293 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1396 0.12 0.5 0.12 0.12 4 4 S. aureus ATCC 25923 0.12 0.5 0.25 0.5 0.12 ≥0.5 S. aureus ATCC 33591 0.5 1 1 1 8 8 S. aureus ATCC 29213 0.25 0.5 0.12 0.5 0.06 ≥0.25 S. aureus WIS-2 0.25 1 0.25 1 0.06 ≥0.25 E. coli ATCC 25922 0.12 0.12 0.12 0.25 0.25 0.25 E. coli 894 0.12 >8 0.25 >8 8 8 K. pneumoniae ATCC 43816 0.5 >32 0.5 >32 4 32 Open in a separate window Organisms used and in vitro susceptibilities to GAR-936, WAY 152,288, and minocycline

Techniques: In Vivo, Infection, Concentration Assay

Journal:

Article Title: In Vivo Pharmacodynamic Activities of Two Glycylcyclines (GAR-936 and WAY 152,288) against Various Gram-Positive and Gram-Negative Bacteria

doi:

Figure Lengend Snippet: Relationship between pharmacokinetic-pharmacodynamic parameters and therapeutic efficacy of GAR-936 (free drug) against S. pneumoniae 1199 in the neutropenic mouse thigh muscle infection model (R2 = 0.82, 0.83, and 0.54 for panels a, b, and c, respectively). (a) time above the 0.5 × MIC versus effect. (b) Log AUC versus effect. (c) Log Cmax versus effect.

Article Snippet: The MBCs were usually 1 to 2 dilutions higher than the MICs except for those for K. pneumoniae ATCC 43816 and E. coli 894. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism GAR-936 WAY 152,288 Minocycline MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) S. pneumoniae ATCC 10813 0.12 0.25 0.12 0.25 0.25 0.5 S. pneumoniae ATCC 49619 0.06 0.06 0.03 0.03 0.06 0.06 S. pneumoniae 1199 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1020 0.06 0.12 0.06 0.12 4 8 S. pneumoniae 1293 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1396 0.12 0.5 0.12 0.12 4 4 S. aureus ATCC 25923 0.12 0.5 0.25 0.5 0.12 ≥0.5 S. aureus ATCC 33591 0.5 1 1 1 8 8 S. aureus ATCC 29213 0.25 0.5 0.12 0.5 0.06 ≥0.25 S. aureus WIS-2 0.25 1 0.25 1 0.06 ≥0.25 E. coli ATCC 25922 0.12 0.12 0.12 0.25 0.25 0.25 E. coli 894 0.12 >8 0.25 >8 8 8 K. pneumoniae ATCC 43816 0.5 >32 0.5 >32 4 32 Open in a separate window Organisms used and in vitro susceptibilities to GAR-936, WAY 152,288, and minocycline

Techniques: Drug discovery, Infection

Journal:

Article Title: In Vivo Pharmacodynamic Activities of Two Glycylcyclines (GAR-936 and WAY 152,288) against Various Gram-Positive and Gram-Negative Bacteria

doi:

Figure Lengend Snippet: Nonlinear regression analysis of the results of the experimental thigh muscle infection on predictors of drug efficacy a

Article Snippet: The MBCs were usually 1 to 2 dilutions higher than the MICs except for those for K. pneumoniae ATCC 43816 and E. coli 894. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism GAR-936 WAY 152,288 Minocycline MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) S. pneumoniae ATCC 10813 0.12 0.25 0.12 0.25 0.25 0.5 S. pneumoniae ATCC 49619 0.06 0.06 0.03 0.03 0.06 0.06 S. pneumoniae 1199 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1020 0.06 0.12 0.06 0.12 4 8 S. pneumoniae 1293 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1396 0.12 0.5 0.12 0.12 4 4 S. aureus ATCC 25923 0.12 0.5 0.25 0.5 0.12 ≥0.5 S. aureus ATCC 33591 0.5 1 1 1 8 8 S. aureus ATCC 29213 0.25 0.5 0.12 0.5 0.06 ≥0.25 S. aureus WIS-2 0.25 1 0.25 1 0.06 ≥0.25 E. coli ATCC 25922 0.12 0.12 0.12 0.25 0.25 0.25 E. coli 894 0.12 >8 0.25 >8 8 8 K. pneumoniae ATCC 43816 0.5 >32 0.5 >32 4 32 Open in a separate window Organisms used and in vitro susceptibilities to GAR-936, WAY 152,288, and minocycline

Techniques: Infection

Journal:

Article Title: In Vivo Pharmacodynamic Activities of Two Glycylcyclines (GAR-936 and WAY 152,288) against Various Gram-Positive and Gram-Negative Bacteria

doi:

Figure Lengend Snippet: Relation between effect of GAR-936 on number of CFU in the thigh after 24 h of therapy in a thigh muscle infection caused by S. pneumoniae ATCC 10813 in neutropenic mice and percent survival after 5 days (2) of treatment. The sigmoid curve represents the dose-effect curve according to the Hill equation. ●, mice for which the effect on the number of CFU was established; each point in the curve represents an individual mouse; ○, mice for which the survival percentage was established (five mice per group).

Article Snippet: The MBCs were usually 1 to 2 dilutions higher than the MICs except for those for K. pneumoniae ATCC 43816 and E. coli 894. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism GAR-936 WAY 152,288 Minocycline MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) MIC (μg/ml) MBC (μg/ml) S. pneumoniae ATCC 10813 0.12 0.25 0.12 0.25 0.25 0.5 S. pneumoniae ATCC 49619 0.06 0.06 0.03 0.03 0.06 0.06 S. pneumoniae 1199 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1020 0.06 0.12 0.06 0.12 4 8 S. pneumoniae 1293 0.06 0.06 0.06 0.06 4 8 S. pneumoniae 1396 0.12 0.5 0.12 0.12 4 4 S. aureus ATCC 25923 0.12 0.5 0.25 0.5 0.12 ≥0.5 S. aureus ATCC 33591 0.5 1 1 1 8 8 S. aureus ATCC 29213 0.25 0.5 0.12 0.5 0.06 ≥0.25 S. aureus WIS-2 0.25 1 0.25 1 0.06 ≥0.25 E. coli ATCC 25922 0.12 0.12 0.12 0.25 0.25 0.25 E. coli 894 0.12 >8 0.25 >8 8 8 K. pneumoniae ATCC 43816 0.5 >32 0.5 >32 4 32 Open in a separate window Organisms used and in vitro susceptibilities to GAR-936, WAY 152,288, and minocycline

Techniques: Infection

Journal: Cell Death & Disease

Article Title: Targeting EGFR-binding protein SLC7A11 enhancing antitumor immunity of T cells via inducing MHC-I antigen presentation in nasopharyngeal carcinoma

doi: 10.1038/s41419-024-07327-9

Figure Lengend Snippet: A Bubble chart of GO enrichment analysis for downregulated genes in SUNE1 cells post-SLC7A11 knockdown. B Upper: qPCR analysis of FAF2 mRNA post-SLC7A11 knockdown. Lower: the effect of knockdown SLC7A11 on the protein expression of FAF2 and MHC-I were verified by Western blot. β-actin were used as loading controls. C Upper: qPCR analysis of FAF2 mRNA following SLC7A11 overexpression. Lower: the effect of SLC7A11 overexpression on the protein expression of FAF2 and MHC-I were verified by Western blot. β-actin were used as loading controls. D Left: qPCR confirmation of FAF2 mRNA knockdown using siFAF2-2/3. Right: the effect of FAF2 knockdown on the protein expression of SLC7A11 and MHC-I were verified by Western blot. Tubulin were used as loading controls. E Immunofluorescence assessment of MHC-I in SUNE1 and 6-10B cells post-FAF2 knockdown. Scale bars, 50 μm. * P < 0.05, *** P < 0.001. The Welch one-way ANOVA test and Games-Howell test in SUNE1 cells, Kruskal–Wallis Test and Dunn’s test in 6-10B cells. Error bars, mean ± SEM . F Immunoblot assessment of SLC7A11, FAF2, and MHC-I in SUNE1 cells post-transfection: control, siSLC7A11, siFAF2, or combined siSLC7A11 and siFAF2. Tubulin were used as loading controls. G Left: Immunoblot of ERAD pathway proteins (VCP, OS9, SYVN1, HERP) in SUNE1 cells post-SLC7A11 knockdown (left), and in 5-8F cells post-SLC7A11 overexpression (right). H Left: Immunoblot of MHC-I in SUNE1 cells transfected with control or FAF2 siRNA for 36 h, then treated with cycloheximide (CHX, 100 μg/ml) for specified durations. Tubulin were used as loading controls. Right: The half-life of the MHC-I protein was calculated. I Immunoblot assessment of MHC-I in SUNE1 and 6-10B cells under control, MG132, or Chloroquine treatments. Tubulin were used as loading controls. J In 5-8F cells overexpressing SLC7A11, IP complexes of MHC-I were immunoblotted for ubiquitination (Ub) under control, VCP inhibitors (NMS-873, 10 μM, MERCK, SML1128), or ERAD inhibitors (Eeyarestatin I, 1.25 μM, MERCK, E1286) treatments. β-actin was used as loading controls.

Article Snippet: Western blotting was conducted in accordance with a previously established protocol [ ], using the following antibodies: SLC7A11 (1:1000, ab175186, Abcam, 35-55kD; 1:1000, 26864-1-AP, Proteintech Group, 55kD; 1:1000, 382036, Zenbio, 55kD), EGFR (1:2000, 26864-1-AP, Proteintech Group), p-EGFR (1:1000, R24173, ZenBioScience), Flag (1:2000, 66008-4-Ig,Proteintech Group), GR (1:5000, 66904-1-Ig, Proteintech Group), TAP1 (1:3000, 11114-1-AP, Proteintech Group), FAF2 (1:3000, 16251-1-AP, Proteintech Group), MHC-I (1:2000, 15240-1-AP, Proteintech Group), SYVN1 (1:1000, 13473-1-AP, Proteintech Group), OS-9 (1:1000, 10061-1-AP, Proteintech Group), VCP (1:2000, 10736-1-AP, Proteintech Group), HERP (1:1000, 10813-1-AP, Proteintech Group), Ubiquitin (1:1000, #3936, CST), β-actin (1:3000, AF7018, Affinity), Tubulin (1:10000, AC021, Abclonal), Histone H3 (1:2000, 68345-1-Ig, Proteintech Group).

Techniques: Knockdown, Expressing, Western Blot, Over Expression, Immunofluorescence, Transfection, Control, Ubiquitin Proteomics

Journal: Nature Communications

Article Title: Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction

doi: 10.1038/s41467-023-40094-3

Figure Lengend Snippet: a Subclustering analysis of fibroblasts. Populations shown at the upper right are cholesteatoma fibroblasts. Populations shown at the lower left are skin fibroblasts. Cholesteatoma fibroblasts are labeled blue, and skin fibroblasts are labeled red at the lower left. Cholesteatoma fibroblasts were associated with five subclusters labeled 1, 7, 8, 10, and 11. b Trajectory mapping performed using Monocle 3. Undifferentiated and differentiated cells are labeled blue and red, respectively. The most differentiated cells were observed in cholesteatoma (labeled red). The differentiated cells were identical to cholesteatoma fibroblasts in subcluster 8. c INHBA expression in fibroblasts in UMAP. Cholesteatoma fibroblasts showed high levels of INHBA expression. The area of high INHBA expression was identical to the area in cholesteatoma fibroblasts in subcluster 8. d Violin plots of INHBA expression in each cluster. Subcluster 8 shows a high INHBA normalized value. e Immunofluorescence staining of cholesteatoma perimatrix. Colocalization of vimentin and INHBA immunofluorescence showed that fibroblasts in the perimatrix expressed INHBA. CD45 was not colocalized with activin A. Leukocytes exhibited no activin A expression. INHBA was labeled with Alexa Fluor 568, vimentin was labeled with Alexa Fluor 488, and CD45 was labeled with Alexa Fluor 647. Scale bars: 10 µm. f INHBA mRNA expression level, corrected for GAPDH mRNA expression, was significantly higher in cholesteatoma fibroblasts than in control skin fibroblasts ( n = 6). Data represent means ± SDs. g IL-1β, PGE 2 , and TNF-α promoted INHBA expression in human primary skin fibroblasts. IL-6 did not promote INHBA expression in ear pinna-derived fibroblasts ( n = 4). The exact p -value between the control and IL-1β is 0.0000003. Data represent means ± SDs. Statistical significance was determined using the ratio paired two-tailed t -test ( f ) and two-tailed unpaired t -test ( g ). Source data are provided as a Source Data file.

Article Snippet: Human primary skin fibroblasts (C-12302; PromoCell, Heidelberg, Germany) were cultured for 3 days in DMEM supplemented with 10% FBS containing recombinant murine IL-1β (1 ng/mL; 201-LB-005; R&D Systems), PGE 2 (10 µM; 165–10813; Wako), TNF-α (50 ng/mL; 210-TA-005; R&D Systems), or IL-6 (50 ng/mL; 201-IL-010; R&D Systems).

Techniques: Labeling, Expressing, Immunofluorescence, Staining, Derivative Assay, Two Tailed Test

Journal: Nature Communications

Article Title: Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction

doi: 10.1038/s41467-023-40094-3

Figure Lengend Snippet: IL-1β, PGE 2 , and TNF-α secreted from infiltrating CD45 + cells, particularly macrophages, induced activin A-expressing pathogenic fibroblasts; the activin A acted in conjunction with RANKL to promote ectopic osteoclastogenesis.

Article Snippet: Human primary skin fibroblasts (C-12302; PromoCell, Heidelberg, Germany) were cultured for 3 days in DMEM supplemented with 10% FBS containing recombinant murine IL-1β (1 ng/mL; 201-LB-005; R&D Systems), PGE 2 (10 µM; 165–10813; Wako), TNF-α (50 ng/mL; 210-TA-005; R&D Systems), or IL-6 (50 ng/mL; 201-IL-010; R&D Systems).

Techniques: Expressing