• At the heart of ferroptosis

  2022-03-24

  

  At the heart of ferroptosis is a process of lethal lipid peroxidation, which is the oxidative addition of molecular oxygen (O2) to lipids, such as polyunsaturated fatty acyl tails in phospholipids. The first descriptions of such enzymatic reactions were in 1955 by Peterson and colleagues [50] and Ro

• br Formation of secretory vesicles and trafficking

  2022-03-24

  

  Formation of secretory vesicles and trafficking toward plasma membrane Insulin and other components of the secretory granules are sorting and providing certain cues for Hydroxyurea off the adjacent TGN membrane, forming immature secretory clathrin coated vesicles (Gehart and Ricci, 2013). Bin/Am

• Eltrombopag br Acknowledgement The authors would like to tha

  2022-03-24

  

  Acknowledgement The authors would like to thank the University of Johannesburg and the National Research Foundation for the financial support. Mr. D Harris and Dr. R Meyer from Shimadzu South Africa are thanked for their technical support. Prof Ian Dubery is thanked for access to the LC-MS instru

• The structures of KDM A revealed a Cys His Zn

  2022-03-24

  

  The structures of KDM4A revealed a Cys-His Zn(II) binding site that is close to the substrate binding spot, which bioinformatic analyses indicated was not present in any other histone demethylase subfamily. Therefore, an alternative method to inhibit the KDM4 family (95) would be to use compounds th

• LDC000067 sale br Materials and methods br Results We

  2022-03-24

  

  Materials and methods Results We studied 16 patients infected with HCV genotypes 1a and 1b, naïve for protease inhibitor-based therapy. All patients, chronically infected, were selected by the Hepatology Department for triple therapy. Most of them had severe liver fibrosis at the beginning of

• Under increased drug pressure more protease variants with mo

  2022-03-24

  

  Under increased drug pressure, more protease variants with more than one substitution will likely become clinically relevant. The accumulation of additional substitutions can allow RAS variants to emerge that alone are not viable, but in combination can rescue the viral fitness. We previously demons

• It is an open question if these

  2022-03-24

  

  It is an open question if these in vitro findings have implications for the use of sGC activators in the in vivo situation and in patients. Assuming that incorporation in de novo synthesised enzyme occurs during therapy, one might speculate that the duration of drug administration has an influence o

• One important aspect about GSK

  2022-03-24

  

  One important aspect about GSK-3 inhibitors is their effect on pluripotency of rhodamine 123 [4]. Many GSK-3 inhibitors are ATP-competitive and suppress both GSK-3alpha and GSK-3beta [476]. BIO was shown to suppress GSK-3 activity and promote Wnt/beta-catenin signaling. This combination of events pr

• Modulation of the cannabinoid system has been

  2022-03-24

  

  Modulation of the cannabinoid system has been reported to exert anti-parkinsonian properties through different mechanisms. On one hand, cannabinoids have neuroprotective properties in different rodent models of PD, both through a CB1/CB2 receptor-independent mechanism (Lastres-Becker et al., 2005) a

• br The mode of binding

  2022-03-24

  

  The mode of binding of ligands to GPR35 As noted above, although kynurenic orexin antagonist is an agonist at GPR35, this is true for neither kynurenine [8] nor kynurenic acid ethyl ester [13]. This implicates a key role for the carboxylate group in binding and/or activation of GPR35. Importantly

• Compounds and were tested for pharmacodynamic effects in

  2022-03-24

  

  Compounds , and were tested for pharmacodynamic effects in a mouse oral glucose tolerance test (oGTT) in wild-type and GPR120 deficient mice, and each compound demonstrated GPR120 mechanism-based effects. Data for compound is shown in , indicating mechanism-based reduction in glucose excursion a

• To further investigate if GPR was the

  2022-03-24

  

  To further investigate if GPR40 was the functional target of these phenylpropiolic Poly (A) Tailing analogs, GW-1100, a selective antagonist of GPR40-mediated Ca2+ elevations in HEK293 cells with an IC50 value equal to 1 μM, was used to inhibit agonist-induced intracellular calcium flux [15]. HEK293

• pHi regulation in astrocytes has been examined primarily in

  2022-03-24

  

  pHi regulation in astrocytes has been examined primarily in cell culture rather than in situ. Two HCO3−-dependent transporters, NBC and Na+-driven Cl-HCO3 exchange (NDCBE), have been described [10,16], in addition to Cl-HCO3 anion exchange (AE) [96]. Culture studies indicate that NHE is the principa

• To confirm the in vitro findings atorvastatin or pravastatin

  2022-03-24

  

  To confirm the in vitro findings, atorvastatin or pravastatin was given to C57BL6/J mice fed with high fat diet. Doses of atorvastatin were set to be 6 mg/kg and 12 mg/kg, which were within clinical therapeutic doses. The results revealed that treatment of atorvastatin but not pravastatin impaired g

• As cardiovascular disease accounts for the majority of

  2022-03-24

  

  As cardiovascular disease accounts for the majority of deaths in subjects with T2D, it is imperative that we better characterize the cardiovascular risks and benefits of the various therapies we prescribe to these individuals to control their glycemia. Indeed, the potential to identify subsets of di

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