Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast Cancer

The relationship between non-alcoholic fatty liver disease (NAFLD) and triple-negative breast cancer (TNBC) has been widely recognized, but the underlying mechanisms are still unknown. The objective of this study was to identify the hub genes associated with NAFLD and TNBC, and to explore the potential co-pathogenesis and prognostic linkage of these two diseases. We used GEO, TCGA, STRING, ssGSEA, and Rstudio to investigate the common differentially expressed genes (DEGs), conduct functional and signaling pathway enrichment analyses, and determine prognostic value between TNBC and NAFLD. GO and KEGG enrichment analyses of the common DEGs showed that they were enriched in leukocyte aggregation, migration and adhesion, apoptosis regulation, and the PPAR signaling pathway. Fourteen candidate hub genes most likely to mediate NAFLD and TNBC occurrence were identified and validation results in a new cohort showed that ITGB2, RAC2, ITGAM, and CYBA were upregulated in both diseases. A univariate Cox analysis suggested that high expression levels of ITGB2, RAC2, ITGAM, and CXCL10 were associated with a good prognosis in TNBC. Immune infiltration analysis of TNBC samples showed that NCF2, ICAM1, and CXCL10 were significantly associated with activated CD8 T cells and activated CD4 T cells. NCF2, CXCL10, and CYBB were correlated with regulatory T cells and myeloid-derived suppressor cells. This study demonstrated that the redox reactions regulated by the NADPH oxidase (NOX) subunit genes and the transport and activation of immune cells regulated by integrins may play a central role in the co-occurrence trend of NAFLD and TNBC. Additionally, ITGB2, RAC2, and ITGAM were upregulated in both diseases and were prognostic protective factors of TNBC; they may be potential therapeutic targets for treatment of TNBC patients with NAFLD, but further experimental studies are still needed

Multinational companies’ coordination mechanism for extending corporate social responsibility to Chinese suppliers

From the global supply chain perspective, this research explores how multinational companies (MNCs) can extend corporate social responsibility (CSR) practices to emerging countries such as China. A two-stage supply chain game model consisting of a Chinese supplier and a MNC is constructed. The study finds that an increase in the level of the Chinese supplier's CSR increases the product demand and the stakeholders' economic profits, but reduces the supplier's economic return; the product demand and the stakeholders' benefits increase along with the product green degree improvement, but the changes in the Chinese supplier's economic profits are jointly affected by the level of CSR and green production efficiency. The supply chain coordination can be achieved based on a revenue sharing contract. Finally, the effects of revenue sharing fraction and supplier's CRS level on product green degree, supplier's revenue and MNC's earnings are discussed by numerical simulation

Risk factors for recurrence of gestational diabetes mellitus in southern Chinese awomen: a retrospective study

Objectives: Predictors of gestational diabetes mellitus (GDM) recurrence (GDMR) was determined in southern Chinese women. Material and methods: A total of 366 women with GDM who had two consecutive singleton deliveries at our hospital between January 2014 and October 2020 were enrolled in the current study. We retrospectively compared the clinical characteristics, fasting plasma glucose level (FPG-1), and oral glucose tolerance test-1h-1 and -2h-1 (OGTT 1hr-1: 1-h post-load glucose level during the first pregnancy and OGTT 2hr-1: 2-h post-load glucose level during the first pregnancy) for the first pregnancy between patients in the GDMR group (n = 166) and the non-GDMR group (n = 210). Results: The incidence of GDMR in the study population was 44.15%. During the first pregnancy, women in the GDMR group had significantly higher OGTT 1h-1, OGTT 2h-1, and FPG-1 + OGTT 1h + 2h-1 compared to the non-GDMR group. When the threshold of the FPG-1 + OGTT 1h + 2h-1 level in the first pregnancy was > 23.6 mmol/L, the specificity for predicting GDMR was 0.85, the sensitivity was 0.45, and the area under the receiver operating characteristic curve (ROC-AUC) was 0.70, indicating a 70% probability of predicting GDMR in the next pregnancy. Logistic regression analysis showed that patients with a combined abnormal FPG-1 + OGTT 1h + 2 h-1 level had a 10-fold increased risk for GDMR in subsequent pregnancies than patients with normal indicators (OR: 10.542, 95% CI: 3.097–35.881; p < 0.0001). Conclusions: The OGTT 1h-1 and OGTT 2h-1 are independent risk factors for GDMR in southern Chinese women. Women with an FPG-1 + OGTT 1h + 2h-1 threshold level > 23.6 mmol/L in the first pregnancy had a 10-fold greater probability of developing GDMR in the second pregnancy than women in the non-GDMR group

The IRF1/GBP5 axis promotes osteoarthritis progression by activating chondrocyte pyroptosis

Background: Osteoarthritis (OA) is a chronic degenerative joint disease that primarily affects middle-aged and elderly individuals. The decline in chondrocyte function plays a crucial role in the development of OA. Inflammasome-mediated chondrocyte pyroptosis is implicated in matrix degradation and cartilage degeneration in OA patients. Guanylate binding protein 5 (GBP5), a member of the GTPase family induced by Interferon-γ (IFN-γ), significantly influences cellular inflammatory responses, including intracellular inflammasome activation and cytokine release. However, the role of GBP5 in chondrocyte pyroptosis and OA progression remains unclear. Methods: In this study, we used tumor necrosis factor-α (TNF-α) to induce inflammation and created an OA mouse model with surgically-induced destabilization of the medial meniscus (DMM). We isolated and cultured primary chondrocytes from the knee joints of suckling C57 mice. TNF-α-stimulated primary chondrocytes served as an in vitro model for OA and underwent RNA sequencing. Chondrocytes were transfected with GBP5-overexpression plasmids and small interfering RNA and were subsequently treated with TNF-α. We assessed the expression of cartilage matrix components (COL2A1 and aggrecan), catabolic factors (MMP9 and MMP13), and NLRP3 inflammasome pathway genes (NLRP3, Caspase1, GSDMD, Pro-IL-1β, and Pro-Caspase1) using RT-qPCR and Western blotting. We analyzed the expression of GBP5, NLRP3, and Caspase1 in the cartilage of DMM-induced post-traumatic OA mice and human OA patients. Immunohistochemistry (IHC) was used to detect the expression of GBP5, NLRP3 and GSDMD in cartilage specimens from OA patients and mouse DMM models. Chondrocyte pyroptosis was assessed using flow cytometry, and the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured with ELISA. We conducted double luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays to confirm the relationship between IRF1 and GBP5. Results: GBP5 expression increased in TNF-α-induced chondrocytes, as revealed by RNA sequencing. GBP5 inhibited COL2A1 and aggrecan expression while promoting the expression of MMP9, MMP13, NLRP3, Caspase1, GSDMD, Pro-IL-1β, and Pro-Caspase1. GBP5 expression also increased in the cartilage of DMM-induced post-traumatic OA mice and human OA patients. Knockout of GBP5 reduced chondrocyte injury in OA mice. GBP5 promoted chondrocyte pyroptosis and the production of IL-1β and IL-18. Additionally, we found that IRF1 bound to the promoter region of GBP5, enhancing its expression. After co-transfected with ad-IRF1 and siGBP5, the expression of pyroptosis-related genes was significantly decreased compared with ad-IRF1 group. Conclusions: The IRF1/GBP5 axis enhances extracellular matrix (ECM) degradation and promotes pyroptosis during OA development, through the NLRP3 inflammasome signaling pathway. The translational potential of this article: This study underscores the significance of the IRF1/GBP5 axis in NLRP3 inflammasome-mediated chondrocyte pyroptosis and osteoarthritic chondrocyte injury. Modulating IRF1 and GBP5 expression could serve as a novel therapeutic target for OA

Parishin treatment alleviates cardiac aging in naturally aged mice

Background: Cardiac aging progressively decreases physiological function and drives chronic/degenerative aging-related heart diseases. Therefore, it is crucial to postpone the aging process of heart and create products that combat aging. Aims & methods: The objective of this study is to examine the effects of parishin, a phenolic glucoside isolated from traditional Chinese medicine Gastrodia elata, on anti-aging and its underlying mechanism. To assess the senescent biomarkers, cardiac function, cardiac weight/body weight ratio, cardiac transcriptomic changes, and cardiac histopathological features, heart tissue samples were obtained from young mice (12 weeks), aged mice (19 months) treated with parishin, and aged mice that were not treated. Results: Parishin treatment improved cardiac function, ameliorated aging-induced cardiac injury, hypertrophy, and fibrosis, decreased cardiac senescence biomarkers p16Ink4a, p21Cip1, and IL-6, and increased the “longevity factor” SIRT1 expression in heart tissue. Furthermore, the transcriptomic analysis demonstrated that parishin treatment alleviated the cardiac aging-related Gja1 downregulation and Cyp2e1, Ccna2, Cdca3, and Fgf12 upregulation in the heart tissues. The correlation analysis suggested a strong connection between the anti-aging effect of parishin and its regulation of gut microbiota and metabolism in the aged intestine. Conclusion: The present study demonstrates the protective role and underlying mechanism of parishin against cardiac aging in naturally aged mice