It has been well demonstrated that hypoxic preconditioning (HPC) can attenuate hypoxia/reoxygenation (H/R)-induced oxidant stress and elicit delayed cardioprotection by upregulating the expression of multiple antioxidative enzymes such as heme oxygenase-1 (HO-1), manganese superoxide dismutase (MnSOD) and so on. However, the underlying mechanisms of HPC-induced upregulation of antioxidative enzymes are not fully understood. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor that regulates expression of several antioxidant genes via binding to the antioxidant response element (ARE) and plays a crucial role in cellular defence against oxidative stress. Here, we wondered whether activation of the Nrf2-ARE pathway is responsible for the induction of antioxidative enzymes by HPC and contributes to the delayed cardioprotection of HPC. Cellular model of HPC from rat heart-derived H9c2 cells was induced 24 h prior to H/R. The results showed that HPC efficiently attenuated H/R-induced viability loss and lactate dehydrogenase leakage. In addition, HPC increased nuclear translocation and ARE binding of Nrf2 during the late phase, upregulated the expression of antioxidative enzymes (HO-1 and MnSOD), inhibited H/R-induced oxidant stress. However, when Nrf2 was specifically knocked down by siRNA, the induction of antioxidative enzymes by HPC was completely abolished and, as a result, the inhibitory effect of HPC on H/R-induced oxidant stress was reversed, and the delayed cardioprotection induced by HPC was also abolished. These results suggest that HPC upregulates antioxidative enzymes through activating the Nrf2-ARE pathway and confers delayed cardioprotection against H/R-induced oxidative stress.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Abnormal ovarian folliculogenesis is the main factor responsible for PCOS. Iron metabolism plays a vital role in endocrine disorder. This study aimed to investigate the potentials of iron metabolism in PCOS and the underlying molecular mechanisms. Mice were injected with dehydroepiandrosterone (DHEA) to establish the PCOS model in-vivo. H & E staining was performed for histological analysis; qRT-PCR and western blot were employed to determine the mRNA and protein expressions. Immunofluorescence was used for mitochondrial staining. Cellular functions were detected using CCK-8 and PI staining assays. Ferric ammonium citrate (FAC) activates the transferrin receptor (TFRC), increases the iron content, and suppresses the cell viability of the human granulosa-like tumor cell line (KGN). However, TFRC knockdown suppressed ferroptosis of KGN cells. Iron uptake mediated the activation of NADPH oxidase 1 (NOX1) signaling, which induced the release of reactive oxygen species (ROS) and mitochondrial damage. Moreover, TFRC activated PTEN induced kinase 1 (PINK1) signaling and induced mitophagy; iron-uptake-induced upregulation of acyl-CoA synthetase long chain family member 4 (ACSL4) was required for mitophagy activation and glutathione peroxidase 4 (GPX4) degradation. Additionally, FAC increased iron uptake and suppressed the folliculogenesis in-vivo. In conclusion, TFRC increased the iron content, mediated the release of ROS, activated mitophagy, and induced lipid peroxidation, which further promoted the ferroptosis of KGN cells. Therefore, the inhibitory effects of TFRC/ NOX1/PINK1/ACSL4 signaling on folliculogenesis can be a potential target for PCOS.

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Background Infertile women often face stigmatization worldwide. This study aimed to investigate the stigma against infertile women in China and to analyze its influencing factors. Methods Of 270 women who were randomly selected from patients receiving adjuvant fertility treatment in Zhejiang Province, China, 254 successfully completed the general information questionnaire, disease information questionnaire, and Chinese version of the infertility stigma scale (ISS). The ISS contained 27 positively worded items, each of which was graded on a 5-point Likert-type scale. Results The total stigma score of female infertility patients was 66.39 ± 21.96. By dividing the number of items, the average score for each ISS item was 2.13 ± 0.81, indicating the presence of stigma. Among the four ISS factors, the social withdrawal score was the highest (2.64 ± 1.05), whereas the family stigma score was the lowest (1.88 ± 0.88). Multiple stepwise regression analysis further revealed that the duration of infertility and monthly income were important predictors of the stigma of infertile women. Conclusions Infertile women experience moderate to high levels of stigma in Zhejiang, China. Thus, supportive psychological interventions and public education are required to change patients’ cognition and assist patients in coping with negative experiences.

Peritoneal metastasis is a major cause of death in patients with advanced gastric carcinoma. DJ-1 is now considered to play an important role in the metastasis of various malignancies. However, it remains largely unclear whether DJ-1 is involved in the development of peritoneal metastasis by gastric carcinoma. In the present study, we showed that the expression of DJ-1 was significantly upregulated in gastric cancer specimens with peritoneal metastasis compared to those without peritoneal metastasis. Knockdown of DJ-1 expression significantly inhibited invasion and migration, in vitro and the in vivo peritoneal metastatic abilities of SGC7901 gastric cancer cells. Moreover, knockdown of DJ-1 also diminished the expression of matrix metallopeptidase (MMP)-2 and MMP-9. All of these effects were reversed by restoration of DJ-1 expression. Following investigation of the pathway through which DJ-1 regulates cell invasion and migration, DJ-1 was found to cause phosphorylation of Akt in SGC7901 gastric cancer cells. Inhibition of the Akt pathway in SGC7901 cells mimicked the effects of DJ-1 knockdown on cell migration, invasion, MMP-2 and MMP-9 expression, and abolished the effects of DJ-1 in promoting SGC7901 cell invasion and migration. Taken together, the present study revealed that DJ-1 plays an important role in the development of peritoneal carcinomatosis from gastric carcinoma, at least partially through activation of the Akt pathway and consequent upregulation of MMP-2 and MMP-9 expression. Thus, DJ-1 may be a potential therapeutic target for peritoneal carcinomatosis of gastric carcinoma.

We have recently shown that DJ-1 is implicated in the delayed cardioprotective effect of hypoxic preconditioning (HPC) against hypoxia/reoxygenation (H/R) injury as an endogenous protective protein. This study aims to further investigate the underlying mechanism by which DJ-1 mediates the delayed cardioprotection of HPC against H/R-induced oxidative stress. Using a well-characterized cellular model of HPC from rat heart-derived H9c2 cells, we found that HPC promoted nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein-1 (Keap1) dissociation and resulted in increased nuclear translocation, antioxidant response element-binding, and transcriptional activity of Nrf2 24 hours after HPC, with subsequent upregulation of manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1), which provided delayed protection against H/R-induced oxidative stress in normal H9c2 cells. However, the aforementioned effects of HPC were abolished in DJ-1-knockdown H9c2 cells, which were restored by restoration of DJ-1 expression. Importantly, we showed that inhibition of the Nrf2 pathway in H9c2 cells mimicked the effects of DJ-1 knockdown and abolished HPC-derived induction of antioxidative enzymes (MnSOD and HO-1) and the delayed cardioprotection. In addition, inhibition of Nrf2 also reversed the effects of restored DJ-1 expression on induction of antioxidative enzymes and delayed cardioprotection by HPC in DJ-1-knockdown H9c2 cells. Taken together, this work revealed that activation of Nrf2 pathway and subsequent upregulation of antioxidative enzymes could be a critical mechanism by which DJ-1 mediates the delayed cardioprotection of HPC against H/R-induced oxidative stress in H9c2 cells.

To investigate the differential expression of microRNA-150-5p (miR-150-5p) and early growth response 1 (EGR1) in myocardial fibrosis (MF) cells, and determine the effect between miR-150-5p and EGR1 on MF. Human MF cells were generated via Trypanosoma cruzi (T. cruzi) infection, a mouse model of MF was generated via angiotensin II. The expression levels of miR-150-5p and EGR1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay. The correlation between miR-150-5p and EGR1 was confirmed by a luciferase reporter assay. The viability, proliferation, and apoptotic rate were detected by cell counting kit-8 (CCK-8), colony-formation and flow cytometry assays. Hematoxylin-eosin (HE) staining and Masson staining visualized the degree of MF. Echocardiography was performed to obtain the levels of left ventricle fractional shortening (LVFS) and left ventricle ejection fraction (LVEF), computer algorithms and a videographics program were used to obtain the levels of left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and ±left ventricular dp/dt maximum (LV dp/dtmax). We found that the expression of miR-150-5p in MF cells was lower than normal cardiomyocytes, while the expression level of EGR1 in MF cells were higher than normal cardiomyocytes. Cell experiments demonstrated that EGR1 and miR-150-5p could influence the development of MF, and the expression of EGR1 in cardiomyocytes was regulated by miR-150-5p directly. Lastly, we confirmed that sh-Egr1 would decrease the severity of MF, while miR-150-5p antagomir could aggravate MF. Our results illustrate the mechanism of MF development, and provide a potential target for MF treatment.