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Recurrent spontaneous abortion (RSA) is a common complication of pregnancy that affects the physical and mental health of pregnant women, and approximately 50% of the mechanisms are unclear. Our previous studies have found that high mobility group box 1 (HMGB1) molecules are highly expressed at the maternal-fetal interface of unexplained recurrent spontaneous abortion (URSA) patients. The purpose of this study was to further detect the expression of HMGB1 and pyroptosis in decidual tissue of URSA patients, and explore the potential mechanism of the protective role of HMGB1 in URSA patients and mouse model. The decidua tissues of 75 URSA patients and 75 women who actively terminated pregnancy were collected, and URSA mouse models were established and treated with HMGB1 inhibitor-aspirin. The expression of HMGB1, and their receptors (RAGE, TLR2, TLR4), pyroptosis-associated proteins (NLRP-3, caspase-1, GSDMD) and NF-κB was examined at the maternal-fetal interface of human and mouse. Our study found that HMGB1, NLRP-3, Caspase-1, GSDMD, RAGE, TLR2 and TLR4 were highly expressed and NF-κB signaling pathway were activated in the decidua tissue of URSA group. Moreover, immune cell disorder and co-localization of HMGB1 and macrophages were found at the maternal-fetal interface of URSA mice. However, HMGB1, TLR2, TLR4, NF-κB, and pyroptosis-associated proteins can be down-regulated by administering low-dose aspirin. These data may indicate that highly expressed HMGB1 was actively secreted by macrophages and then activated pyroptosis through the TLR2/TLR4-NF-κB pathway to cause aseptic inflammation, leading to the occurrence and development of URSA. Moreover, low-dose aspirin can reduce HMGB1 protein levels of serum and decidual in URSA.

The aim of the present study was to investigate the antioxidant response mechanism of epigallocatechin‑3‑gallate (EGCG) in H2O2‑induced mouse renal tubular epithelial cells (MRTECs). The cultured MRTECs were divided into normal, H2O2 (control) and EGCG treatment groups. The MTT assay was used to assess cell viability, and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), immunocytochemical and western blot analyses were performed to detect the expression of nuclear factor erythroid 2‑related factor 2 (Nrf2) and γ‑glutamyl cysteine synthetase (γ‑GCS). EGCG was able to mitigate H2O2‑mediated cell damage. The RT‑qPCR results demonstrated that EGCG was able to upregulate the gene expression of Nrf2 and γ‑GCS in MRTECs in a dose‑dependent manner. The immunocytochemistry and western blot analyses demonstrated that EGCG was able to increase the protein expression of Nrf2 and γ‑GCS in MRTECs in a dose‑dependent manner. Oxidative stress may lead to a decrease in the viability of MRTECs, while EGCG was able to promote the expression of Nrf2 and γ‑GCS in MRTECs, thereby improving the antioxidant capacity of the cells and promoting the repair of oxidative stress injury.

C-ski is a complicated regulating factor for fibroblast proliferation and an important co-repressor of Smad3. Although inhibiting Smad3 activity can markedly promote wound healing because Smad3 mediates the role of transforming growth factor-beta in inhibiting cell proliferation and inducing cell apoptosis; there has been no report on whether c-ski is expressed during wound healing and the relationship between its expression and wound healing. By establishing animal models of normal and radiation-impaired wound healing and using immunohistochemistry, in situ hybridization, and reverse transcription-polymerase chain reaction, we found that c-ski was expressed after wounding and reached its peak on day 9 and then significantly decreased. C-ski was present in all repair cells, and was especially prominent in fibroblasts. Compared with the control side, the irradiated side showed a lower expression of c-ski on postwound days 3-9, but higher on day 15, and not significantly different after the wound was healed. The expression of Smad3 was in contrast to the c-ski and cellular proliferation was similar to that of c-ski expression. The apoptosis index was significantly higher on the irradiated side on days 3-9 compared with the control side. In vitro, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide results showed that c-ski could reverse the inhibitory role of Smad3 on fibroblast proliferation. Flow cytometry analysis found that c-ski also diminished fibroblast apoptosis induced by Smad3 transfection. These results suggest that there is not only obvious expression of this regulatory protein but there is also a significant change in the levels of c-ski during wound healing. Its in vivo expression pattern and experiments in vitro suggest that c-ski may be involved in tissue repair by repressing Smad3 activity. Radiation can reduce c-ski and increase Smad3 expression, resulting in elevated Smad3 activity, resulting in diminished cell proliferation, cell apoptosis, and wound-healing delays.

To study effects of Bcl-xLin the pancreatic β-cell, two transgenic lines were produced using different forms of the rat insulin promoter. Bcl-xLexpression in β-cells was increased 2- to 3-fold in founder (Fd) 1 and over 10-fold in Fd 2 compared with littermate controls. After exposure to thapsigargin (10 μM for 48 h), losses of cell viability in islets of Fd 1 and Fd 2 Bcl-xLtransgenic mice were significantly lower than in islets of wild-type mice. Unexpectedly, severe glucose intolerance was observed in Fd 2 but not Fd 1 Bcl-xLmice. Pancreatic insulin content and islet morphology were not different from control in either transgenic line. However, Fd 2 Bcl-xLislets had impaired insulin secretory and intracellular free Ca2+([Ca2+]i) responses to glucose and KCl. Furthermore, insulin and [Ca2+]iresponses to pyruvate methyl ester (PME) were similarly reduced as glucose in Fd 2 Bcl-xLislets. Consistent with a mitochondrial defect, glucose oxidation, but not glycolysis, was significantly lower in Fd 2 Bcl-xLislets than in wild-type islets. Glucose-, PME-, and α-ketoisocaproate-induced hyperpolarization of mitochondrial membrane potential, NAD(P)H, and ATP production were also significantly reduced in Fd 2 Bcl-xLislets. Thus, although Bcl-xLpromotes β-cell survival, high levels of expression of Bcl-xLresult in reduced glucose-induced insulin secretion and hyperglycemia due to a defect in mitochondrial nutrient metabolism and signaling for insulin secretion.

Background Recent studies suggest a role of the proteasome activator, REGγ, in cancer progression. Since there are limited numbers of known REGγ targets, it is not known which cancers and pathways are associated with REGγ. Methods REGγ protein expressions in four different cancers were investigated by immunohistochemistry (IHC) analysis. Following NCBI Gene Expression Omnibus (GEO) database search, microarray platform validation, differential expressions of REGγ in corresponding cancers were statistically analyzed. Genes highly correlated with REGγ were defined based on Pearson's correlation coefficient. Functional links were estimated by Ingenuity Core analysis. Finally, validation was performed by RT-PCR analysis in established cancer cell lines and IHC in human colon cancer tissues Results Here, we demonstrate overexpression of REGγ in four different cancer types by micro-tissue array analysis. Using meta-analysis of publicly available microarray databases and biological studies, we verified elevated REGγ gene expression in the four types of cancers and identified genes significantly correlated with REGγ expression, including genes in p53, Myc pathways, and multiple other cancer-related pathways. The predicted correlations were largely consistent with quantitative RT-PCR analysis. Conclusions This study provides us novel insights in REGγ gene expression profiles and its link to multiple cancer-related pathways in cancers. Our results indicate potentially important pathogenic roles of REGγ in multiple cancer types and implicate REGγ as a putative cancer marker.