Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis.
In December 2019, an outbreak of novel coronavirus pneumonia spread over Wuhan, Hubei Province, China, which then developed into a significant global health public event, giving rise to substantial economic losses. We downloaded throat swab expression profiling data of COVID-19 positive and negative patients from the Gene Expression Omnibus (GEO) database to mine novel diagnostic biomarkers. XGBoost was used to construct the model and select feature genes. Subsequently, we constructed COVID-19 classifiers such as MARS, KNN, SVM, MIL, and RF using machine learning methods. We selected the KNN classifier with the optimal MCC value from these classifiers using the IFS method to identify 24 feature genes. Finally, we used principal component analysis to classify the samples and found that the 24 feature genes could effectively be used to classify COVID-19-positive and negative patients. Additionally, we analyzed the possible biological functions and signaling pathways in which the 24 feature genes were involved by GO and KEGG enrichment analyses. The results demonstrated that these feature genes were primarily enriched in biological functions such as viral transcription and viral gene expression and pathways such as Coronavirus disease-COVID-19. In summary, the 24 feature genes we identified were highly effective in classifying COVID-19 positive and negative patients, which could serve as novel markers for COVID-19.
Bisphenol A (BPA) is a chemical used in numerous consumer products that is able to interfere with the mammalian endocrine system. The aim of the present study was to investigate the effects of BPA on male mouse reproductive cells following prenatal to postnatal exposure. In addition, the influence of BPA was detected on the expression levels of β‑catenin and dickkopf WNT signaling pathway inhibitor 1 (DKK‑1) during the differentiation of spermatogenic cells in the mouse testes. β‑catenin and DKK‑1 are two important proteins of the Wnt/β‑catenin signaling pathway. On gestational day 1, pregnant ICR mice were randomly divided into four groups: A dimethyl sulfoxide group, and three groups treated with various concentrations of BPA (0.5, 10, and 50 µg/kg). BPA was administered from gestational day 1 to weaning on postnatal day (PND) 42. The number of murine pups and the male:female ratio was recorded for each group. On PND 42, the male pups were sacrificed and their wet weights and testicular coefficients were measured. Immunohistochemical and western blot analyses were used to detect the protein expression of β‑catenin and DKK‑1 in the testicular tissue samples of the six‑week‑old male mice. The results indicated that the number of murine pups, as well as the testicular viscera coefficient of the male mice, significantly decreased in the BPA‑treated groups, as compared with the control group (P<0.05, P<0.01); however, no significant difference was observed in the male/female ratio in the BPA‑treated groups, as compared with the control group (P>0.05). The results from the immunohistochemical and western blot analyses indicated that the protein expression of β‑catenin and DKK‑1 were significantly increased in the BPA‑treated groups, as compared with the control group, and the distribution of spermospore and Leydig cells also increased in the testes. These results suggest that high expression levels of β‑catenin and DKK‑1 may participate in BPA‑induced pathogenesis in male mouse reproductive cells.
Objective To investigate the value of ultrasound in the dynamic assessment of lung injury after acute paraquat poisoning. Methods A prospective observational study was performed on patients with paraquat poisoning from admission to day 28 or discharge. Ultrasound assessment of the lungs was performtyed every 48 hours. The correlation of the lung ultrasound score (LUS) with other indicators was analyzed. Results Twenty-six patients were enrolled, with an average age of 46 ± 16 years. The average toxic dose was 95 ± 51 mL. The intensive care unit (ICU) stay averaged 9 ± 8 days, and the 28-day mortality was 88.5%. There was a significant negative correlation between LUS and oxygenation index (rho = −0.896) and a significant positive correlation between LUS and carbon dioxide concentration (rho = 0.567). Lung ultrasound and computed tomography imaging correlated closely. Conclusion Lung ultrasound can reflect changes in lung status in patients with paraquat poisoning and can be used to evaluate lung injury in these patients. Trial registration: ChiCTR, ChiCTR-DDD-16010211. Registered 21 December 2016, http://www.chictr.org.cn/listbycreater.aspx .
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