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• The CASP1 rs2409062 polymorphism correlates with a higher risk of RA. • This polymorphism relates with females, age ≥ 55, CRP-positive, or DAS28 < 3.20. • The level of CASP1 protein in the plasma of RA cases rised significantly. • RA cases displayed greater levels of CASP1 mRNA versus the control group. The goals of present research are to investigate if the genetic polymorphisms in the caspase-1 (CASP1) gene are associated with the risk of rheumatoid arthritis (RA) and the clinical characteristics of the illness in Han patients from China. Our team studied the CASP1 rs2409062 A/G polymorphisms in 1095 healthy controls and 805 RA patients, while the genotype was identified via a custom-by-design 48-Plex single nucleotide polymorphism (SNP) scan™ Kit. The mRNA expression levels of the CASP1 in 40 RA cases and 40 healthy controls were detected by qRT-PCR, while blood plasma levels of the CASP1 in 40 RA cases and 40 paired controls measured via ELISA. Our research showed that the CASP1 rs2409062 A/G polymorphisms were related to an elevated risk for RA. By stratified analysis, our team discovered a remarkably elevated RA risk in females sufferers, age ≥ 55, CRP-positive, or DAS28 < 3.20. In contrast to the control group, the mean level of CASP1 protein in the plasma of RA cases rised significantly. Moreover, RA cases displayed significantly greater levels of CASP1 mRNA versus the control group (P < 0.05). Those outcomes reveal that the CASP1 rs2409062 A/G gene polymorphisms are associated with an elevated risk for RA in a Chinese Han population. [ABSTRACT FROM AUTHOR]

Graphical abstract PDMS sponge supported DMAP on polymer brushes can be used as highly efficient recyclable base catalyst and ligand for various organic transformations and provide much better catalytic activities and selectivities than free DMAP in water. Highlights • PDMS sponge DMAP has high catalytic activity and selectivity in water. • The polymer brush nano-structures on sponge can provide excellent reactive sites. • The catalyst's easy preparation by solid-phase synthetic strategy. • Recyclable catalyst and ligand, and easy to scale up by a flow reactor. • This hydrophobic PDMS sponge will be an excellent catalyst carrier in water. Abstract The successfully developed polydimethylsiloxane (PDMS, a stable hydrophobic polymer material) sponge supported DMAP can be used as base catalyst and ligand to facilitate a series of organic transformations with high efficiency and good reusability in water. This PDMS sponge DMAP can provide much better catalytic activities and selectivities than free DMAP in water. Through an easy-to-build continuous flow reactor, the PDMS sponge DMAP facilitated reactions can be facilely scaled up. This porous hydrophobic PDMS sponge material will be a promising carrier for the development of highly efficient recyclable catalysts in water. [ABSTRACT FROM AUTHOR]

Abstract: Acetaldehyde, the major metabolite of ethanol, which is far more toxic and reactive than ethanol, may be responsible for alcohol-induced cardiac damage. This study was designed to examine the impact of facilitated acetaldehyde metabolism using transfection of human aldehyde dehydrogenase-2 (ALDH2) transgene on acetaldehyde- and ethanol-induced cell injury. Fetal human cardiac myocytes were transfected with ALDH2, the efficacy of which was verified by flow cytometry, Western blot and ALDH2 activity assays. Generation of reactive oxygen species (ROS) was detected using 5-(6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate (CM-H2DCFDA). Apoptosis was evaluated by 4′,6′-diamidino-2′-phenylindoladihydrochloride (DAPI) fluorescence microscopy, quantitative DNA fragmentation ELISA and caspase 3 activity. Acetaldehyde and ethanol elicited overt ROS generation and apoptosis in human cardiac myocytes following 24–48 h of incubation. Immunostaining revealed activation of the MAP kinase cascades ERK1/2, SAPK/JNK and p38 MAP kinase in acetaldehyde-treated myocytes. Interestingly, ALDH2 transgene significantly attenuated acetaldehyde-induced ROS generation, apoptosis and phosphorylation of ERK1/2 and SAPK/JNK. Time-dependent response (0–12 h) revealed ROS accumulation and activation of MAP kinases prior to acetaldehyde-induced apoptosis. In addition, acetaldehyde-induced ROS generation and apoptosis were antagonized by non-enzymatic antioxidants. Our results suggested that ALDH2 transgene overexpression may effectively alleviate acetaldehyde-elicited cell injury through an ERK1/2 and SPAK/JNK-dependent mechanism. Our data are consistent with the notion of acetaldehyde as a contributor to alcoholic cardiomyopathy and implicate the therapeutic potential of ALDH2 enzyme in alcoholic complications. [Copyright &y& Elsevier]

Sirtuins are a family of highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent enzymes. Among the sirtuins, SIRT1 and SIRT6 participate in the regulation of endothelial functions and play significant roles in the physiological and pathological processes of cardiovascular diseases (CVD). Recently, our study found that minute cholesterol crystals (CC) can be endocytosed by endothelial cells and further impair endothelial functions. Since previous studies have reported that angiotensin-converting enzyme (ACE2) involves Angiotensin (Ang) II-induced inflammation in endothelial cells, this study was designed to investigate the role of SIRT1 and SIRT6 in CC-induced variation of ACE2 expression and the related mechanism between SIRT6 and ACE2. We found that ACE2 is involved in CC-induced endothelial dysfunction, which inhibits decreases in nitric oxide (NO) level and endothelial nitric oxide synthase (eNOS) activity and increases in inflammatory factors and adhesion molecules. Besides, SIRT1 and SIRT6 regulated the protein expression of ACE2 in CC-stimulated human umbilical vein endothelial cells (HUVECs). Moreover, bioinformatics analysis from the Enrichr database indicated that activating transcription factor 2 (ATF2), is highly correlated with genes that significantly upregulated after infection with the SIRT6 adenovirus vector. In CC-induced HUVECs, ACE2 expression was up-regulated in cells transfected with ATF2 siRNA. However, further mechanism studies revealed that overexpression of SIRT6 decreases the accumulation of p-ATF2 in the nucleus, but did not affect p-ATF2 expression in the cytoplasm. Taken together, these data indicated that SIRT6 regulates ACE2 might via inhibiting the accumulation of nucleus p-ATF2 in CC-induced endothelial dysfunction. • ACE2 was involved in CC-induced endothelial dysfunction. • SIRT1 and SIRT6 contributed to regulating the protein expression of ACE2 in CC-stimulated endothelial cells. • SIRT6 regulated ACE2 with intranuclear p-ATF2, but not affecting p-ATF2 expression in the cytoplasm. [ABSTRACT FROM AUTHOR]