st3gal1  (R&D Systems)


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    R&D Systems st3gal1
    St3gal1, supplied by R&D Systems, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    ceritinib dihydrochloride  (Bio-Techne corporation)


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    Bio-Techne corporation ceritinib dihydrochloride
    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or <t>Ceritinib</t> (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
    Ceritinib Dihydrochloride, supplied by Bio-Techne corporation, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Average 93 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    ceritinib dihydrochloride - by Bioz Stars, 2024-07
    93/100 stars

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    1) Product Images from "Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss"

    Article Title: Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss

    Journal: bioRxiv

    doi: 10.1101/2023.07.18.549357

    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or Ceritinib (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
    Figure Legend Snippet: A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or Ceritinib (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.

    Techniques Used: Injection, Inhibition

    A) Effects of vehicle (Veh), Semaglutide (Sem), Ceritinib (Cer), and Ceritinib + Semaglutide (Com) on gene expression in epididymal white adipose tissue (n=4/group). B,C) 24 hours after Cer or Veh treatment (B), genes in the melanocortin pathways are not significantly affected (n=5/group), but after 5 days days of treatment (C), changes in gene expression are consistent with homeostatic responses to negative energy balance rather than a causal involvement with decreased food intake (n=4/group). D) Targeted quantitative peptidomic analysis of the mouse hypothalamus did not reveal significant changes likely to drive reduced food intake (n=4/group). E, F) After 5 days of gene expression, Cer or Com treatment induces significant changes in hypothalamic gene expression relative to Veh (E) that consistently involve upregulation of the PI3K/AKT pathway (F, n=4/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
    Figure Legend Snippet: A) Effects of vehicle (Veh), Semaglutide (Sem), Ceritinib (Cer), and Ceritinib + Semaglutide (Com) on gene expression in epididymal white adipose tissue (n=4/group). B,C) 24 hours after Cer or Veh treatment (B), genes in the melanocortin pathways are not significantly affected (n=5/group), but after 5 days days of treatment (C), changes in gene expression are consistent with homeostatic responses to negative energy balance rather than a causal involvement with decreased food intake (n=4/group). D) Targeted quantitative peptidomic analysis of the mouse hypothalamus did not reveal significant changes likely to drive reduced food intake (n=4/group). E, F) After 5 days of gene expression, Cer or Com treatment induces significant changes in hypothalamic gene expression relative to Veh (E) that consistently involve upregulation of the PI3K/AKT pathway (F, n=4/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.

    Techniques Used: Expressing

    A, B) After both 24 hours of treatment with Veh or Cer (A) or 5 days of treatment with Veh, Sem, Cer, or Com, Glp1r is consistently upregulated in Cer-treated animals. C) Experimental schematic of 24 hour incubation with Veh or Cer in human hypothalamic cultures, followed by qPCR, or by administration of Semaglutide (Sem) and calcium imaging. D) Cer significantly increases the expression of several genes of interest, notably GLP1R (n=4/group). E) Representative calcium imaging traces of neurons incubated with Vehicle (grey) or Ceritinib (orange), and treated with Sem. F) Responses to Sem are significantly (p<0.05) potentiated by pre-treatment with Cer (n=62, N=3) relative to vehicle (n=57, N=3). Data represent mean ± SEM (qPCR) and mean with 95% CI (calcium imaging); *p<0.05, **p<0.01, ***p<0.001.
    Figure Legend Snippet: A, B) After both 24 hours of treatment with Veh or Cer (A) or 5 days of treatment with Veh, Sem, Cer, or Com, Glp1r is consistently upregulated in Cer-treated animals. C) Experimental schematic of 24 hour incubation with Veh or Cer in human hypothalamic cultures, followed by qPCR, or by administration of Semaglutide (Sem) and calcium imaging. D) Cer significantly increases the expression of several genes of interest, notably GLP1R (n=4/group). E) Representative calcium imaging traces of neurons incubated with Vehicle (grey) or Ceritinib (orange), and treated with Sem. F) Responses to Sem are significantly (p<0.05) potentiated by pre-treatment with Cer (n=62, N=3) relative to vehicle (n=57, N=3). Data represent mean ± SEM (qPCR) and mean with 95% CI (calcium imaging); *p<0.05, **p<0.01, ***p<0.001.

    Techniques Used: Incubation, Imaging, Expressing

    st3gal1  (R&D Systems)


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    R&D Systems st3gal1
    St3gal1, supplied by R&D Systems, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    6905 primescript rt reagent kit takara bio  (TaKaRa)


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    TaKaRa 6905 primescript rt reagent kit takara bio
    6905 Primescript Rt Reagent Kit Takara Bio, supplied by TaKaRa, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    86/100 stars

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    st3gal1  (R&D Systems)


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    R&D Systems st3gal1
    St3gal1, supplied by R&D Systems, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    94/100 stars

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    Structured Review

    abberior instruments imspector version 16 1 6905
    Imspector Version 16 1 6905, supplied by abberior instruments, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    86/100 stars

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    ceritinib dihydrochloride  (Bio-Techne corporation)


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    Bio-Techne corporation ceritinib dihydrochloride
    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or <t>Ceritinib</t> (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
    Ceritinib Dihydrochloride, supplied by Bio-Techne corporation, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/ceritinib dihydrochloride/product/Bio-Techne corporation
    Average 93 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    ceritinib dihydrochloride - by Bioz Stars, 2024-07
    93/100 stars

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    1) Product Images from "Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss"

    Article Title: Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss

    Journal: bioRxiv

    doi: 10.1101/2023.07.18.549357

    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or Ceritinib (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
    Figure Legend Snippet: A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or Ceritinib (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.

    Techniques Used: Injection, Inhibition

    A) Effects of vehicle (Veh), Semaglutide (Sem), Ceritinib (Cer), and Ceritinib + Semaglutide (Com) on gene expression in epididymal white adipose tissue (n=4/group). B,C) 24 hours after Cer or Veh treatment (B), genes in the melanocortin pathways are not significantly affected (n=5/group), but after 5 days days of treatment (C), changes in gene expression are consistent with homeostatic responses to negative energy balance rather than a causal involvement with decreased food intake (n=4/group). D) Targeted quantitative peptidomic analysis of the mouse hypothalamus did not reveal significant changes likely to drive reduced food intake (n=4/group). E, F) After 5 days of gene expression, Cer or Com treatment induces significant changes in hypothalamic gene expression relative to Veh (E) that consistently involve upregulation of the PI3K/AKT pathway (F, n=4/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
    Figure Legend Snippet: A) Effects of vehicle (Veh), Semaglutide (Sem), Ceritinib (Cer), and Ceritinib + Semaglutide (Com) on gene expression in epididymal white adipose tissue (n=4/group). B,C) 24 hours after Cer or Veh treatment (B), genes in the melanocortin pathways are not significantly affected (n=5/group), but after 5 days days of treatment (C), changes in gene expression are consistent with homeostatic responses to negative energy balance rather than a causal involvement with decreased food intake (n=4/group). D) Targeted quantitative peptidomic analysis of the mouse hypothalamus did not reveal significant changes likely to drive reduced food intake (n=4/group). E, F) After 5 days of gene expression, Cer or Com treatment induces significant changes in hypothalamic gene expression relative to Veh (E) that consistently involve upregulation of the PI3K/AKT pathway (F, n=4/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.

    Techniques Used: Expressing

    A, B) After both 24 hours of treatment with Veh or Cer (A) or 5 days of treatment with Veh, Sem, Cer, or Com, Glp1r is consistently upregulated in Cer-treated animals. C) Experimental schematic of 24 hour incubation with Veh or Cer in human hypothalamic cultures, followed by qPCR, or by administration of Semaglutide (Sem) and calcium imaging. D) Cer significantly increases the expression of several genes of interest, notably GLP1R (n=4/group). E) Representative calcium imaging traces of neurons incubated with Vehicle (grey) or Ceritinib (orange), and treated with Sem. F) Responses to Sem are significantly (p<0.05) potentiated by pre-treatment with Cer (n=62, N=3) relative to vehicle (n=57, N=3). Data represent mean ± SEM (qPCR) and mean with 95% CI (calcium imaging); *p<0.05, **p<0.01, ***p<0.001.
    Figure Legend Snippet: A, B) After both 24 hours of treatment with Veh or Cer (A) or 5 days of treatment with Veh, Sem, Cer, or Com, Glp1r is consistently upregulated in Cer-treated animals. C) Experimental schematic of 24 hour incubation with Veh or Cer in human hypothalamic cultures, followed by qPCR, or by administration of Semaglutide (Sem) and calcium imaging. D) Cer significantly increases the expression of several genes of interest, notably GLP1R (n=4/group). E) Representative calcium imaging traces of neurons incubated with Vehicle (grey) or Ceritinib (orange), and treated with Sem. F) Responses to Sem are significantly (p<0.05) potentiated by pre-treatment with Cer (n=62, N=3) relative to vehicle (n=57, N=3). Data represent mean ± SEM (qPCR) and mean with 95% CI (calcium imaging); *p<0.05, **p<0.01, ***p<0.001.

    Techniques Used: Incubation, Imaging, Expressing

    r d 6905 ab  (Tocris)


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    Tocris r d 6905 ab
    R D 6905 Ab, supplied by Tocris, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    r d 6905 ab  (Tocris)


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    Tocris r d 6905 ab
    R D 6905 Ab, supplied by Tocris, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Biotechnology Information nn 6905
    Nn 6905, supplied by Biotechnology Information, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    pigment grade copper phthalocyanine heliogen blue l 6905  (BASF)

     
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    BASF pigment grade copper phthalocyanine heliogen blue l 6905
    Pigment Grade Copper Phthalocyanine Heliogen Blue L 6905, supplied by BASF, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    recombinant human st3gal1  (Bio-Techne corporation)


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    Bio-Techne corporation recombinant human st3gal1
    Recombinant Human St3gal1, supplied by Bio-Techne corporation, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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  • 94
    R&D Systems st3gal1
    St3gal1, supplied by R&D Systems, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or <t>Ceritinib</t> (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
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    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or <t>Ceritinib</t> (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
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    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or <t>Ceritinib</t> (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
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    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or <t>Ceritinib</t> (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
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    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or <t>Ceritinib</t> (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
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    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or <t>Ceritinib</t> (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
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    Bio-Techne corporation recombinant human st3gal1
    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or <t>Ceritinib</t> (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.
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    Image Search Results


    A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or Ceritinib (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.

    Journal: bioRxiv

    Article Title: Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss

    doi: 10.1101/2023.07.18.549357

    Figure Lengend Snippet: A) Experimental schematic to test the acute effects of vehicle (Veh; DMSO) or Ceritinib (Cer) injection in mice fed for 1 week of 60% high fat diet (HFD) or a nutritionally matched control diet (CD) with an experimental end-point 24 hours later. B) Mice fed CD gained weight at a similar rate regardless of injection condition (n=10/group), whereas HFD-fed mice significantly lost weight when treated with Cer (n=5/group), suggesting it acts to normalise excess energy balance rather than inducing nausea or non-specific toxicity. C) Experimental schematic of the long-term effects of Veh, Cer, Semaglutide (Sem) or a combination of Ceritinib and Semaglutide (Com) given every 48 hours to DIO mice. D) Sem, Cer, and Com treatment all induce significant body weight loss relative to Veh controls, with the greatest effect observed in the Com group (n=12/group). E) Weight loss is associated with a significant improvement in glucose homeostasis as revealed by an intraperitoneal glucose tolerance test (n=4/group). F,G) EchoMRI measurements (n=12/group) reveal that fat mass is dramatically reduced by Sem, Cer, and Com treatment (F), and lean mass is also modestly but significantly reduced in these groups (G). H-I) The loss in fat mass is accompanied by a significant reduction in plasma concentrations of leptin (H) and cholesterol (I) in Cer and Com groups (n=12/group). J-M) Plasma concentrations of c-reactive protein (CRP) were not elevated in any treatment group relative to Veh (J), but GDF-15 (K) and the liver enzymes aspartate aminotransferase (AST, L) and alanine aminotransferase (ALT, M), were moderately but significantly elevated in only the Cer group, suggesting that drug toxicity does not drive the dramatic weight loss observed with Com treatment (n=12/group). N) Experimental schematic of metabolic measurements in DIO mice over 5 days of treatment. O) Body weight recorded prior to daily injection (n=8/group) followed a similar trajectory to earlier studies (D). P-S) In contrast to previous reports in Alk deficient mice, acute Alk inhibition with Cer or Com had no effect on energy expenditure (Q-R) but significantly reduced food intake (S-T) (n=8/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.

    Article Snippet: After the acclimatisation period, intraperitoneal injections (10 mL/kg injection volume) of vehicle (DMSO), 10 mg/kg Ceritinib dihydrochloride, 40 μg/kg Semaglutide, 20 mg/kg YNT-185 (Bio-Techne), or a combination of 10 mg/kg Ceritinib dihydrochloride and 40 μg/kg Semaglutide were performed every day at around 10:00h during which body weights were recorded.

    Techniques: Injection, Inhibition

    A) Effects of vehicle (Veh), Semaglutide (Sem), Ceritinib (Cer), and Ceritinib + Semaglutide (Com) on gene expression in epididymal white adipose tissue (n=4/group). B,C) 24 hours after Cer or Veh treatment (B), genes in the melanocortin pathways are not significantly affected (n=5/group), but after 5 days days of treatment (C), changes in gene expression are consistent with homeostatic responses to negative energy balance rather than a causal involvement with decreased food intake (n=4/group). D) Targeted quantitative peptidomic analysis of the mouse hypothalamus did not reveal significant changes likely to drive reduced food intake (n=4/group). E, F) After 5 days of gene expression, Cer or Com treatment induces significant changes in hypothalamic gene expression relative to Veh (E) that consistently involve upregulation of the PI3K/AKT pathway (F, n=4/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.

    Journal: bioRxiv

    Article Title: Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss

    doi: 10.1101/2023.07.18.549357

    Figure Lengend Snippet: A) Effects of vehicle (Veh), Semaglutide (Sem), Ceritinib (Cer), and Ceritinib + Semaglutide (Com) on gene expression in epididymal white adipose tissue (n=4/group). B,C) 24 hours after Cer or Veh treatment (B), genes in the melanocortin pathways are not significantly affected (n=5/group), but after 5 days days of treatment (C), changes in gene expression are consistent with homeostatic responses to negative energy balance rather than a causal involvement with decreased food intake (n=4/group). D) Targeted quantitative peptidomic analysis of the mouse hypothalamus did not reveal significant changes likely to drive reduced food intake (n=4/group). E, F) After 5 days of gene expression, Cer or Com treatment induces significant changes in hypothalamic gene expression relative to Veh (E) that consistently involve upregulation of the PI3K/AKT pathway (F, n=4/group). Data represent mean ± SEM; *p<0.05, **p<0.01, ***p<0.001.

    Article Snippet: After the acclimatisation period, intraperitoneal injections (10 mL/kg injection volume) of vehicle (DMSO), 10 mg/kg Ceritinib dihydrochloride, 40 μg/kg Semaglutide, 20 mg/kg YNT-185 (Bio-Techne), or a combination of 10 mg/kg Ceritinib dihydrochloride and 40 μg/kg Semaglutide were performed every day at around 10:00h during which body weights were recorded.

    Techniques: Expressing

    A, B) After both 24 hours of treatment with Veh or Cer (A) or 5 days of treatment with Veh, Sem, Cer, or Com, Glp1r is consistently upregulated in Cer-treated animals. C) Experimental schematic of 24 hour incubation with Veh or Cer in human hypothalamic cultures, followed by qPCR, or by administration of Semaglutide (Sem) and calcium imaging. D) Cer significantly increases the expression of several genes of interest, notably GLP1R (n=4/group). E) Representative calcium imaging traces of neurons incubated with Vehicle (grey) or Ceritinib (orange), and treated with Sem. F) Responses to Sem are significantly (p<0.05) potentiated by pre-treatment with Cer (n=62, N=3) relative to vehicle (n=57, N=3). Data represent mean ± SEM (qPCR) and mean with 95% CI (calcium imaging); *p<0.05, **p<0.01, ***p<0.001.

    Journal: bioRxiv

    Article Title: Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss

    doi: 10.1101/2023.07.18.549357

    Figure Lengend Snippet: A, B) After both 24 hours of treatment with Veh or Cer (A) or 5 days of treatment with Veh, Sem, Cer, or Com, Glp1r is consistently upregulated in Cer-treated animals. C) Experimental schematic of 24 hour incubation with Veh or Cer in human hypothalamic cultures, followed by qPCR, or by administration of Semaglutide (Sem) and calcium imaging. D) Cer significantly increases the expression of several genes of interest, notably GLP1R (n=4/group). E) Representative calcium imaging traces of neurons incubated with Vehicle (grey) or Ceritinib (orange), and treated with Sem. F) Responses to Sem are significantly (p<0.05) potentiated by pre-treatment with Cer (n=62, N=3) relative to vehicle (n=57, N=3). Data represent mean ± SEM (qPCR) and mean with 95% CI (calcium imaging); *p<0.05, **p<0.01, ***p<0.001.

    Article Snippet: After the acclimatisation period, intraperitoneal injections (10 mL/kg injection volume) of vehicle (DMSO), 10 mg/kg Ceritinib dihydrochloride, 40 μg/kg Semaglutide, 20 mg/kg YNT-185 (Bio-Techne), or a combination of 10 mg/kg Ceritinib dihydrochloride and 40 μg/kg Semaglutide were performed every day at around 10:00h during which body weights were recorded.

    Techniques: Incubation, Imaging, Expressing