Association between the Composite Dietary Antioxidant Index and Atherosclerotic Cardiovascular Disease in Postmenopausal Women: A Cross-Sectional Study of NHANES Data, 2013-2018.

The relationship between composite dietary antioxidant index (CDAI) levels and the risk of atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women is unknown. In total, 3109 women from the National Health and Nutrition Examination Survey 2013-2018 were included in this cross-sectional study. We evaluated the association between CDAI levels and the risk of ASCVD by using three logistic regression models and restricted cubic splines. A stratified analysis and sensitivity analysis were also conducted. The restricted cubic splines exhibited an L-shaped dose-response association between CDAI levels and the ASCVD risk. Logistic regression analysis found that CDAI levels were negatively associated with the occurrence of ASCVD. The ORs associated with a per-SD increase in CDAI were 0.67 (95% CI: 0.51-0.88) for ASCVD risk. Similarly, women in the group with high CDAI levels were less likely to have ASCVD (OR = 0.71, 95% CI: 0.50-0.98) compared to those in the group with low CDAI levels. When the CDAI levels were divided into quartiles, it was found that the ORs for ASCVD with CDAI levels in Q2 (-1.04-1.11), Q3 (1.11-3.72), and Q4 (3.72-43.87) were 0.63 (0.44, 0.90), 0.64 (0.42, 0.94), and 0.51 (0.27, 0.97), respectively, compared to those with CDAI levels in Q1 (-6.83--1.04). In addition, age, high-density lipoprotein cholesterol levels, and smoking behaviors acted as potential modifiers, and ORs were more significant in women aged 40-69 years, in individuals with low high-density lipoprotein cholesterol levels, and in smokers (p for interaction <0.05). These findings may offer valuable insights into the role of CDAI levels in the development of ASCVD among postmenopausal women.

SsATG8 and SsNBR1 mediated-autophagy is required for fungal development, proteasomal stress response and virulence in Sclerotinia sclerotiorum.

Autophagy plays vital roles in the interaction between the necrotrophic fungal pathogen Sclerotinia sclerotiorum and its hosts. However, so far, only little is known about the impacts of autophagy machinery in S. sclerotiorum per se on the fungal morphogenesis and pathogenesis. Here, through functional genomic approaches, we showed that SsATG8, one of the core components of the autophagy machinery, and its interactor SsNBR1, an autophagy cargo receptor, are important for vegetative growth, sclerotial formation, oxalic acid (OA) production, compound appressoria development, and virulence of S. sclerotiorum. Complementation assays with chimeric fusion constructs revealed that both LDS [AIM (ATG8 interacting motif) / LIR (LC3-interacting region) docking site] and UDS [UIM (ubiquitin-interacting motif) docking site] sites of the SsATG8 are required for its functions in autophagy and pathogenesis. Importantly, ΔSsatg8 and ΔSsnbr1 mutants showed enhanced sensitivity to the exogenous treatment with the proteasome inhibitors bortezomib and carfilzomib, and ΔSsnbr1 mutant had decreased expression of SsATG8 under the proteasomal stress conditions, suggesting that a cross-talk exists between ubiquitin-proteasome and selective autophagy pathways, which enables downstream protein degradation to proceed properly during diverse biological processes. Collectively, our data indicate that SsATG8- and SsNBR1-mediated autophagy is crucial for S. sclerotiorum development, proteasomal stress response and virulence.

Engineered T Cell Therapy for Gynecologic Malignancies: Challenges and Opportunities.

Gynecologic malignancies, mainly including ovarian cancer, cervical cancer and endometrial cancer, are leading causes of death among women worldwide with high incidence and mortality rate. Recently, adoptive T cell therapy (ACT) using engineered T cells redirected by genes which encode for tumor-specific T cell receptors (TCRs) or chimeric antigen receptors (CARs) has demonstrated a delightful potency in B cell lymphoma treatment. Researches impelling ACT to be applied in treating solid tumors like gynecologic tumors are ongoing. This review summarizes the preclinical research and clinical application of engineered T cells therapy for gynecologic cancer in order to arouse new thoughts for remedies of this disease.

Mesenchymal stem cells protect against neonatal rat hyperoxic lung injury.

OBJECTIVES: Bronchopulmonary dysplasia (BPD) is a significant global health problem and currently lacks effective therapy. We established a neonatal rat model of BPD to investigate therapeutic potential of bone marrow-derived mesenchymal stem cells (BMSCs) in neonatal hyperoxic lung injury. METHODS: BMSCs were isolated, identified, and transfected by lentiviral vector carrying green fluorescent protein gene in vitro. Neonatal Sprague-Dawley rats were injected intravenously with either BMSCs or phosphate-buffered saline following 95% oxygen exposure, and assessed for the survival rate and alveolar injury during recovery. RESULTS: Treatment with BMSCs after oxygen exposure for 7 days improved survival of neonatal rat during recovery. BMSCs protected against neonatal rat hyperoxic lung injury during recovery as demonstrated by enhanced expression of AQP5 and SP-C, likely due to the suppression of alveolar cell apoptosis and lung inflammation responses to oxygen with up-regulation of the expression of BCL-2 gene and down-regulation of the expression of BAX gene and stimulation of vascular endothelial growth factor and so on. CONCLUSIONS: BMSCs protect against O2-mediated injury partially through stimulation of potent mediators that participate in tissue repair.

Bone marrow mesenchymal stem cells attenuate lung inflammation of hyperoxic newborn rats.

BPD is a significant global health problem and currently lacks effective therapy. We established a neonatal rat model of BPD to investigate therapeutic potential of BMSCs in neonatal lung disease. BMSCs were isolated, identified, and transfected by lentiviral vector carrying GFP gene in vitro. Neonatal rats were injected intravenously with either BMSCs or PBS after they had been already exposed to high oxygen for seven days, and assessed on post-injection day 3, day 7, and day 14 for weight gaining, lung histology, radical alveolar counts, and lung cytokine level. BMSCs were positive for CD29, CD44, and CD90 whereas negative for CD34, CD45, CD11b and with differentiation potential into osteoblasts, adipocytes, and chondrocytes. BMSCs expressed GFP after transfected by lentivirus. After injection, BMSCs exert their therapeutic benefit of improving weight gaining, preventing alveolar growth arrest, and suppressing lung inflammation of neonatal rats. Intravenous delivery of BMSCs in newborn rats conferred protection from hyperoxia-induced lung injury, and one of the effects of BMSCs treatment is suppressing lung inflammation.

Multiple mesodermal lineage differentiation of Apodemus sylvaticus embryonic stem cells in vitro.

BACKGROUND: Embryonic stem (ES) cells have attracted significant attention from researchers around the world because of their ability to undergo indefinite self-renewal and produce derivatives from the three cell lineages, which has enormous value in research and clinical applications. Until now, many ES cell lines of different mammals have been established and studied. In addition, recently, AS-ES1 cells derived from Apodemus sylvaticus were established and identified by our laboratory as a new mammalian ES cell line. Hence further research, in the application of AS-ES1 cells, is warranted. RESULTS: Herein we report the generation of multiple mesodermal AS-ES1 lineages via embryoid body (EB) formation by the hanging drop method and the addition of particular reagents and factors for induction at the stage of EB attachment. The AS-ES1 cells generated separately in vitro included: adipocytes, osteoblasts, chondrocytes and cardiomyocytes. Histochemical staining, immunofluorescent staining and RT-PCR were carried out to confirm the formation of multiple mesodermal lineage cells. CONCLUSIONS: The appropriate reagents and culture milieu used in mesodermal differentiation of mouse ES cells also guide the differentiation of in vitro AS-ES1 cells into distinct mesoderm-derived cells. This study provides a better understanding of the characteristics of AS-ES1 cells, a new species ES cell line and promotes the use of Apodemus ES cells as a complement to mouse ES cells in future studies.