International journal of molecular medicine
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Multicenter Study
Association of six genetic variants with myocardial infarction.
Although various genes that confer susceptibility to myocardial infarction (MI) have been identified for Caucasian populations in genome-wide association studies (GWAS), genetic variants related to this condition in Japanese individuals have not been identified definitively. The aim of the present study was to examine an association of MI in Japanese individuals with 29 polymorphisms identified as susceptibility loci for MI or coronary artery disease in Caucasian populations by meta-analyses of GWAS. The study subjects comprised 1,824 subjects with MI and 2,329 controls. ⋯ Comparisons of allele frequencies by the χ(2) test revealed that rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1, FDR=0.0007), rs4977574 of the CDKN2B antisense RNA 1 gene (CDKN2B-AS1, FDR=0.0038), rs264 of the lipoprotein lipase gene (LPL, FDR=0.0061), rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1, FDR=0.0118), rs9319428 of the fms-related tyrosine kinase 1 gene (FLT1, FDR=0.0118) and rs12413409 of the cyclin and CBS domain divalent metal cation transport mediator 2 gene (CNNM2, FDR=0.0300) were significantly associated with MI. Multivariate logistic regression analysis with adjustment for covariates revealed that rs9369640 (P=0.0005; odds ratio, 0.89), rs4977574 (P=0.0001; odds ratio, 1.50), rs264 (P=0.0405; odds ratio, 0.85), rs599839 (P=0.0003; odds ratio, 0.68), rs9319428 (P=0.0155; odds ratio, 1.20) and rs12413409 (P=0.0076; odds ratio, 0.66) were significantly (P<0.05) associated with MI. PHACTR1, CDKN2B-AS1, LPL, PSRC1, FLT1 and CNNM2 may thus be susceptibility loci for MI in Japanese individuals.
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Endoplasmic reticulum (ER) stress and inflammation induced by obesity lead to adipocyte dysfunction, with the impairment of the insulin pathway. Recent studies have indicated that understanding the physiological role of autophagy is of great significance. In the present study, an in vitro model was used in which 3T3-L1 adipocytes were pre-loaded with palmitate (PA) to generate artificially hypertrophied mature adipocytes. ⋯ In conclusion, our data indicate that PA elicits a ER stress-JNK-autophagy axis, and that this confers a pro-survival effect against PA-induced cell death and stress in hypertrophied adipocytes. The JNK-dependent activation of autophagy diminishes PA-induced inflammation. Therefore, the stimulation of autophagy may become a method with which to attenuate adipocyte dysfunction and inflammation.
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Xuebijing (XBJ) is a type of traditional Tibetan medicine, and previous pharmacological studies have shown that the ethanol extract is derived from Chuanxiong, Chishao, Danshen and Honghua. Chuanxiong, Chishao, Danshen and Honghua possesses potent anti-inflammatory activity, and has been used in the treatment of inflammatory infectious diseases. In the present study, we investigated the effects of XBJ on pulmonary permeability and lung injury in cecal ligation and puncture (CLP)-induced sepsis in rats. ⋯ The histological results also demonstrated the attenuation effect of XBJ on CLP-induced lung inflammation. The results of the present study indicated that XBJ has a significantly reduced CLP-induced lung permeability by upregulating Tollip expression. The protective effects of XBJ suggest its therapeutic potential in CLP-induced acute lung injury treatment.
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Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are characteristic of AML. Zinc finger protein 382 (ZNF382) has been suggested to be a tumor suppressor gene possibly regulated by promoter hypermethylation in various types of human cancer. ⋯ The epigenetic inactivation of ZNF382 by promoter hypermethylation can be observed in AML cell lines and pediatric AML samples. Therefore, our study suggests that ZNF382 may be considered a putative tumor suppressor gene in pediatric AML. However, further studies focusing on the mechanisms responsible for ZNF382 downregulation in pediatric leukemia are required.
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Intestinal barrier dysfunction occurs in critical illnesses and involves the inflammatory and hypoxic injury of intestinal epithelial cells. Researchers are still defining the underlying mechanisms and evaluating therapeutic strategies for restoring intestinal barrier function. The anti-inflammatory drug, emodin, has been shown to exert a protective effect on intestinal barrier function; however, its mechanisms of action remain unknown. ⋯ The results revealed that emodin markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS and subjected to HR. Emodin also markedly alleviated the damage caused by LPS and HR (manifested by a decrease in the expression of the TJ protein, ZO-1), and inhibited the expression of HIF-1α, IκB-α, NF-κB and COX-2 in a dose-dependent manner. In conclusion, our data suggest that emodin attenuates LPS- and HR-induced intestinal epithelial barrier dysfunction by inhibiting the HIF-1α and NF-κB signaling pathways and preventing the damage caused to the TJ barrier (shown by the decrease in the expression of ZO-1).