Mechanotransduction in alveolar epithelial cells subjected to mechanical strain

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XRCC7 rs#7003908 Polymorphism and Helicobacter pylori Infection-Related Gastric Antrum Adenocarcinoma

The X-ray repair cross-complementing group 7 (XRCC7) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. To determine whether XRCC7 rs#7003908 polymorphism (XRCC7P) is associated with Helicobacter pylori (H. pylori) infection-related gastric antrum adenocarcinoma (GAA) risk, we conducted a hospital-based case-control study, including 642 patients with pathologically confirmed GAA and 927 individually matched controls without any evidence of tumours or precancerous lesions, among Guangxi population. Increased risks of GAA were observed for individuals with cagA positive (odds ratio (OR) 6.38; 95% confidence interval (CI) 5.03–8.09). We also found that these individuals with the genotypes of XRCC7 rs#7003908 G alleles (XRCC7-TG or -GG) featured increasing risk of GAA (ORs 2.80 and 5.13, resp.), compared with the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT). GAA risk, moreover, did appear to differ more significantly among individuals featuring cagA-positive status, whose adjusted ORs (95% CIs) were 15.74 (10.89–22.77) for XRCC7-TG and 38.49 (22.82–64.93) for XRCC7-GG, respectively. Additionally, this polymorphism multiplicatively interacted with XRCC3 codon 241 polymorphism with respect to HCC risk (ORinteraction=1.49). These results suggest that XRCC7P may be associated with the risk of Guangxiese GAA related to cagA

Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model

The remodeling of the extracellular matrix (ECM) in the parenchyma plays an important role in the development of acute respiratory distress syndrome (ARDS), a disease characterized by lung injury. Although it is clear that TGF-β1 can modulate the expression of the extracellular matrix (ECM) through intracellular signaling molecules such as Smad3, its role as a therapeutic target against ARDS remains unknown. In this study, a rat model was established to mimic ARDS via intratracheal instillation of lipopolysaccharide (LPS). A selective inhibitor of Smad3 (SIS3) was intraperitoneally injected into the disease model, while phosphate-buffered saline (PBS) was used in the control group. Animal tissues were then evaluated using histological analysis, immunohistochemistry, RT-qPCR, ELISA, and western blotting. LPS was found to stimulate the expression of RAGE, TGF-β1, MMP2, and MMP9 in the rat model. Moreover, treatment with SIS3 was observed to reverse the expression of these molecules. In addition, pretreatment with SIS3 was shown to partially inhibit the phosphorylation of Smad3 and alleviate symptoms including lung injury and pulmonary edema. These findings indicate that SIS3, or the blocking of TGF-β/Smad3 pathways, could influence remodeling of the ECM and this may serve as a therapeutic strategy against ARDS