Antiviral Effectivity of Favipiravir Against Peste Des Petits Ruminants Virus Is Mediated by the JAK/STAT and PI3K/AKT Pathways

Antiviral Effectivity of Favipiravir Against Peste Des Petits Ruminants Virus Is Mediated by the JAK/STAT and PI3K/AKT Pathways

Peste des petits ruminants virus (PPRV), belonging to the genus Morbillivirus within the household Paramyxoviridae, causes extreme infectious illness in small ruminants and has been quickly spreading in lots of elements of Africa, the Center East, and Asia.
Though vaccination is taken into account to be an efficient technique of controlling PPR, the heat-sensitive nature of the vaccines towards PPRV enormously limits their utility in areas with a sizzling local weather. Within the current research, we investigated the anti-PPRV results of favipiravir and sought to determine the underlying mechanisms in vitro utilizing the Vero cell line.
MTT assays, Western blotting, oblique immunofluorescence assays, virus plaque formation assays, and qRT-PCR had been used to evaluate the consequences of favipiravir on the life cycle of PPRV and the expression of RNA-dependent RNA polymerase (RdRp). Moreover, the expression ranges of JAK1, STAT1, phosphorylated (p)-STAT1, PI3K, AKT, and p-AKT, in addition to these of signaling molecules appearing downstream of the JAK/STAT and PI3K/AKT signaling pathways, had been decided by Western blotting and qRT-PCR.
The outcomes indicated that, in PPRV-infected, favipiravir-treated Vero cells, the attachment, invasion, replication, and launch of PPRV had been considerably inhibited, as was the expression of RdRp, in comparison with that in untreated PPRV-infected cells.
Moreover, in favipiravir-treated cells, the expression of JAK1 and STAT1 was downregulated, whereas that of p-STAT1 was considerably upregulated. Equally, the expression ranges of PKR, IRF9, ISG54, and MxA proteins which are related to innate antiviral exercise in host cells had been additionally markedly elevated. Furthermore, with favipiravir therapy, the expression of PI3K and p-AKT and the p-AKT/AKT ratio had been considerably decreased, whereas the expression of AKT was noticeably upregulated.
The expression of GSK3, NF-κB p65, p-NF-κB p65, and BAD was additionally elevated with favipiravir therapy, whereas the expression of CREB, p-CREB, p-GSK3, and Bcl-2 was barely decreased. As well as, all of the p-GSK3/GSK3, p-CREB/CREB, p-NF-κB/NF-κB, and p-BAD/BAD ratios had been considerably decreased in favipiravir-treated cells.
These outcomes implied that the antiviral effectivity of favipiravir towards PPRV is mediated by the JAK/STAT and PI3K/AKT pathways and that favipiravir has potential to be used as an efficient antiviral agent towards PPRV.

Glycogen synthase kinase-3β inactivation promotes cervical most cancers development, invasion, and drug resistance

Human papillomavirus (HPV) infection-dependent cervical most cancers is without doubt one of the most typical gynecological cancers and infrequently turns into aggressive, with fast proliferation, invasion/migration, and drug resistance.
Right here, 135 recent human CSCC tissue specimens, comprising: 21 adjoining normals (AN), 30 cervical-intraepithelial-neoplasia (CIN1-3 ), 45 CSCC, and 39 medicine (chemo-radiation)-resistant cervical tumor (DRCT) tissues had been included.
HPV-positive (HeLa, SiHa), HPV-negative (C33A), and cisplatin-resistant (CisR-HeLa/-SiHa/-C33A) cell strains had been used for in vitro research. HPV16/18 oncoproteins E6/E7, pERK1/2, and glycogen synthase kinase-3 (GSK3) and the matrix metalloproteinases (MMPs) MMP-9/-2 had been assessed utilizing immunohistochemistry, WB, and gelatin zymography.
HPV16/18 an infection was noticed in 16.7% of the CIN1-3 , 77.8% of the CSCC, and 89.7% of DRCT samples. Whole and inactive GSK3β expressions had been related to total CSCC development (p = 0.039 and p = 0.024, respectively) and chemoresistance (p = 0.004 and p = 0.014, respectively).
Constructive correlations had been noticed, between the expression of E6 and pGSK3β expression (p = 0.013); E6 and CSCC development (p<0.0001)/ drug resistance (p = 0.0001). CisR-HeLa/-SiHa was extra depending on pGSK3β, and activation of GSK3 by SMIs (iAkt), therapy with nimbolide, or knockdown of E6/E7 decreased cisplatin-resistance and promoted apoptosis. Therefore, the activation of GSK3β with nimbolide and iAkt may be exploited for therapeutic interventions of cervical most cancers. This text is protected by copyright. All rights reserved.

G protein-coupled receptor kinase 2 is crucial to allow vasoconstrictor-mediated arterial clean muscle proliferation

Hypertension is related to elevated manufacturing and circulation of vasoconstrictors, leading to enhanced signalling by their cognate G protein-coupled receptors (GPCR). Extended vasoconstrictor GPCR signalling will increase arterial contraction and stimulates signalling pathways that promote vascular clean muscle cell (VSMC) proliferation, contributing to the event of atherosclerotic plaques, re-stenosis lesions and vascular remodelling.
GPCR signalling by phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) promotes VSMC proliferation. In VSMC, G protein-coupled receptor kinase 2 (GRK2) is thought to manage quite a few vasoconstrictor GPCRs and their downstream signalling pathways.
As GRK2 is implicated in controlling numerous elements of mobile development, we examined whether or not GRK2 might have an effect on VSMC proliferation. Utilizing two indices of cell development, we present that PI3K inhibition and depletion of GRK2 expression produced the same ablation of pro-proliferative vasoconstrictor-stimulated VSMC development.
Moreover, GRK2-knockdown ablated the sustained part of endothelin-1 and angiotensin-II-stimulated Akt phosphorylation, while the height (5 min) part was unaffected. Conversely, the GRK2 inhibitor compound 101 didn’t have an effect on vasoconstrictor-driven Akt phosphorylation.
Vasoconstrictor-stimulated phosphorylation of the Akt substrates GSK3α and GSK3β was ablated following RNAi-mediated GRK2 depletion, or after PI3K inhibition. Furthermore, GRK2 knockdown prevented endothelin-1 and angiotensin-II from rising cyclin D1 expression.
These knowledge counsel GRK2 expression is crucial to facilitate vasoconstrictor-driven VSMC proliferation by its potential to advertise environment friendly extended PI3K-Akt signalling, and thus relieve the GSK3-mediated block on cell biking. Contemplating VSMC GRK2 expression will increase early within the improvement of hypertension, this highlights the potential for GRK2 to advertise VSMC development and exacerbate hypertensive pathophysiological vascular remodelling.

Publicity to Perfluoro-Octanoic Acid Related With Upstream Uncoupling of the Insulin Signaling in Human Hepatocyte Cell Line

Perfluoro-alkyl substances (PFAS) are chemical pollution with prevalent stability and environmental persistence. Publicity to PFAS, notably perfluoro-octanoic acid (PFOA), has been related to elevated diabetes-related cardiovascular mortality in topics residing areas of excessive environmental contamination, nevertheless the precise pathogenic mechanism stays elusive.
Antiviral Effectivity of Favipiravir Against Peste Des Petits Ruminants Virus Is Mediated by the JAK/STAT and PI3K/AKT Pathways
Right here we used HepG2 cells, an in vitro mannequin of human hepatocyte, to research the potential position of PFOA publicity within the alteration of hepatic glucose metabolism. HepG2 cells had been uncovered for 24 hours to PFOA at rising focus from Zero to 1000 ng/mL after which stimulated with 100 nm Insulin (Ins).
The ensuing impact on glycogen synthesis, glucose uptake and Glut-Four glucose transporter translocation was then evaluated by, respectively, Periodic Acid Schiff (PAS) staining, 2-deoxyglucose (2-DG) uptake assay and immunofluorescence.
Publicity to PFOA was related to decreased glycogen synthesis and glucose uptake, at focus equal or higher than, respectively, 0,1 ng/mL and 10 ng/mL, with parallel impaired membrane translocation of Glut-Four upon Ins stimulation. Western blot evaluation confirmed early uncoupling of Insulin Receptor (InsR) activation from the downstream Akt and GSK3 phosphorylation.
Antiviral Effectivity of Favipiravir Against Peste Des Petits Ruminants Virus Is Mediated by the JAK/STAT and PI3K/AKT Pathways
Computational docking evaluation disclosed the potential stabilizing impact of PFOA on the advanced between InsR and GM3 ganglioside, beforehand proven to be related to the low grade persistent inflammation-related insulin resistance.

Glycogen Synthase Kinase 3 Alpha (GSK3A) Antibody

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Description: A Rabbit polyclonal antibody against Rat Glycogen Synthase Kinase 3 Alpha (GSK3a)

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Description: A Rabbit polyclonal antibody against Human Glycogen Synthase Kinase 3 Alpha (GSK3a)

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Description: A Rabbit polyclonal antibody against Rat Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with PE.

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Description: A Rabbit polyclonal antibody against Rat Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with APC.

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Description: A Rabbit polyclonal antibody against Rat Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with Cy3.

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Description: A Rabbit polyclonal antibody against Rat Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with HRP.

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Description: A Rabbit polyclonal antibody against Human Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with PE.

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Description: A Rabbit polyclonal antibody against Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with PE.

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Description: A Rabbit polyclonal antibody against Rat Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with FITC.

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Description: A Rabbit polyclonal antibody against Human Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with APC.

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Description: A Rabbit polyclonal antibody against Human Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with Cy3.

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Description: A Rabbit polyclonal antibody against Human Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with FITC.

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Human), HRP

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Description: A Rabbit polyclonal antibody against Human Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with HRP.

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Mouse), APC

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Description: A Rabbit polyclonal antibody against Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with APC.

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Mouse), Cy3

4-PAA630Mu01-Cy3
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Description: A Rabbit polyclonal antibody against Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with Cy3.

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Mouse), FITC

4-PAA630Mu01-FITC
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Description: A Rabbit polyclonal antibody against Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with FITC.

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Mouse), HRP

4-PAA630Mu01-HRP
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Description: A Rabbit polyclonal antibody against Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with HRP.

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

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Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

RPU41701-100ug 100ug
EUR 514.8

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

RPU41701-1mg 1mg
EUR 2282.8

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

RPU41701-50ug 50ug
EUR 413.6

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

RPU41702-100ug 100ug
EUR 552.2

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

RPU41702-1mg 1mg
EUR 2446.6

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

RPU41702-50ug 50ug
EUR 443.3

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

RPA630Hu01 10ug
EUR 167

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

4-RPA630Hu01
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  • 100 ug
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  • 200 ug
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  • 5 mg
Description: Recombinant Human Glycogen Synthase Kinase 3 Alpha expressed in: E.coli

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

RPA630Mu01 10ug
EUR 179

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

4-RPA630Mu01
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  • 100 ug
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  • 5 mg
Description: Recombinant Mouse Glycogen Synthase Kinase 3 Alpha expressed in: E.coli

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

RPA630Ra01 10ug
EUR 187

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

4-RPA630Ra01
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  • 100 ug
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  • 200 ug
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  • 5 mg
Description: Recombinant Rat Glycogen Synthase Kinase 3 Alpha expressed in: E.coli

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2018527-001mg 0.01mg
EUR 170

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2018527-005mg 0.05mg
EUR 305

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2018527-01mg 0.1mg
EUR 470

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2018527-02mg 0.2mg
EUR 570

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2018527-05mg 0.5mg
EUR 1085

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2018243-001mg 0.01mg
EUR 165

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2018243-005mg 0.05mg
EUR 295

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2018243-01mg 0.1mg
EUR 440

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2018243-02mg 0.2mg
EUR 535

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2018243-05mg 0.5mg
EUR 1020

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2028945-001mg 0.01mg
EUR 175

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2028945-005mg 0.05mg
EUR 320

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2028945-01mg 0.1mg
EUR 490

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2028945-02mg 0.2mg
EUR 595

Recombinant Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2028945-05mg 0.5mg
EUR 1130

GSK3A (GFP-tagged) - Human glycogen synthase kinase 3 alpha (GSK3A)

RG208698 10 µg Ask for price

Glycogen Synthase Kinase 3 Alpha Phospho-Ser21 (GSK3A pS21) Antibody

abx333153-100ul 100 ul
EUR 560.4

Glycogen Synthase Kinase 3 Alpha Phospho-Ser21 (GSK3A pS21) Antibody

20-abx329708
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  • 100 ug
  • 50 ug

Glycogen Synthase Kinase 3 Alpha Phospho-Ser21 (GSK3A pS21) Antibody

abx329708-100g 100 µg Ask for price

Glycogen Synthase Kinase 3 Alpha Phospho-Ser21 (GSK3A pS21) Antibody

abx329708-20g 20 µg
EUR 187.5

Glycogen Synthase Kinase 3 Alpha Phospho-Ser21 (GSK3A pS21) Antibody

abx329708-50g 50 µg
EUR 250

Glycogen Synthase Kinase 3 Alpha Phospho-Ser21 (GSK3A pS21) Antibody

abx333153-100g 100 µg Ask for price

Glycogen Synthase Kinase 3 Alpha Phospho-Ser21 (GSK3A pS21) Antibody

abx333153-20g 20 µg
EUR 412.5

Glycogen Synthase Kinase 3 Alpha Phospho-Ser21 (GSK3A pS21) Antibody

abx333153-50g 50 µg Ask for price

Rat Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099221-10x96Tests 10x96Tests
EUR 1445

Rat Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099221-10x96TestsMBS2090685AbPairsSupportPack110x96Tests 10x96Tests+MBS2090685(AbPairsSupportPack1,10x96Tests)
EUR 1570

Rat Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099221-5x96Tests 5x96Tests
EUR 915

Rat Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099221-5x96TestsMBS2090685AbPairsSupportPack15x96Tests 5x96Tests+MBS2090685(AbPairsSupportPack1,5x96Tests)
EUR 990

Gsk3a (untagged) - Mouse glycogen synthase kinase 3 alpha (Gsk3a), (10ug)

MC216926 10 µg Ask for price

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Rat), Biotinylated

4-PAA630Ra01-Biotin
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  • 100ul
  • 10ml
  • 1ml
  • 200ul
  • 20ul
Description: A Rabbit polyclonal antibody against Rat Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with Biotin.

Human Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099219-10x96Tests 10x96Tests
EUR 1340

Human Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099219-10x96TestsMBS2090685AbPairsSupportPack110x96Tests 10x96Tests+MBS2090685(AbPairsSupportPack1,10x96Tests)
EUR 1465

Human Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099219-5x96Tests 5x96Tests
EUR 855

Human Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099219-5x96TestsMBS2090685AbPairsSupportPack15x96Tests 5x96Tests+MBS2090685(AbPairsSupportPack1,5x96Tests)
EUR 925

Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099220-10x96Tests 10x96Tests
EUR 1515

Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099220-10x96TestsMBS2090685AbPairsSupportPack110x96Tests 10x96Tests+MBS2090685(AbPairsSupportPack1,10x96Tests)
EUR 1640

Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099220-5x96Tests 5x96Tests
EUR 960

Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a) Antibody Pair Kit (with Standard)

MBS2099220-5x96TestsMBS2090685AbPairsSupportPack15x96Tests 5x96Tests+MBS2090685(AbPairsSupportPack1,5x96Tests)
EUR 1035

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Rat), APC-Cy7

4-PAA630Ra01-APC-Cy7
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  • 100ul
  • 10ml
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  • 200ul
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Description: A Rabbit polyclonal antibody against Rat Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with APC-Cy7.

Glycogen Synthase Kinase 3 alpha, beta (GSK3a/b)

MBS609175-01mL 0.1mL
EUR 690

Glycogen Synthase Kinase 3 alpha, beta (GSK3a/b)

MBS609175-5x01mL 5x0.1mL
EUR 2955

Glycogen Synthase Kinase 3 alpha, beta (GSK3a/b)

MBS632730-10Blots 10Blots
EUR 665

Glycogen Synthase Kinase 3 alpha, beta (GSK3a/b)

MBS632730-5x10Blots 5x10Blots
EUR 2830

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Human), Biotinylated

4-PAA630Hu01-Biotin
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  • 100ul
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  • 200ul
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Description: A Rabbit polyclonal antibody against Human Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with Biotin.

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Mouse), Biotinylated

4-PAA630Mu01-Biotin
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  • 100ul
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Description: A Rabbit polyclonal antibody against Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with Biotin.

Rat Glycogen Synthase Kinase 3 Alpha (GSK3a) Protein

20-abx167726
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  • 100 ug
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  • 1 mg
  • 200 ug
  • 50 ug

Rat Glycogen Synthase Kinase 3 Alpha (GSK3a) Protein

abx167726-1ml 1 ml
EUR 225

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Human), APC-Cy7

4-PAA630Hu01-APC-Cy7
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  • 100ul
  • 10ml
  • 1ml
  • 200ul
  • 20ul
Description: A Rabbit polyclonal antibody against Human Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with APC-Cy7.

Glycogen Synthase Kinase 3 Alpha (GSK3a) Polyclonal Antibody (Mouse), APC-Cy7

4-PAA630Mu01-APC-Cy7
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  • 100ul
  • 10ml
  • 1ml
  • 200ul
  • 20ul
Description: A Rabbit polyclonal antibody against Mouse Glycogen Synthase Kinase 3 Alpha (GSK3a). This antibody is labeled with APC-Cy7.

PE-Linked Polyclonal Antibody to Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2045243-01mL 0.1mL
EUR 250

PE-Linked Polyclonal Antibody to Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2045243-02mL 0.2mL
EUR 325

PE-Linked Polyclonal Antibody to Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2045243-05mL 0.5mL
EUR 600

PE-Linked Polyclonal Antibody to Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2045243-1mL 1mL
EUR 735

PE-Linked Polyclonal Antibody to Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2045243-5mL 5mL
EUR 2105

APC-Linked Polyclonal Antibody to Glycogen Synthase Kinase 3 Alpha (GSK3a)

MBS2045244-01mL 0.1mL
EUR 250
Constantly, long run therapy with glucosyl-ceramide synthase inhibitor PDMP was in a position to largely restore glycogen synthesis, glucose uptake and Glut-Four translocation upon Ins stimulation in HepG2 uncovered to PFOA. Our knowledge help a novel pathogenic mechanism linking publicity to PFOA to derangement of hepatocyte cell metabolism.

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