Vaccines have become one of the most effective strategies to deal with various infectious diseases and chronic noninfectious diseases, such as SARS virus, Novel Coronavirus, cancer, etc. However, recent studies have found that the neutralizing antibody titers induced by vaccines would drop to half level or even lower after vaccination. In this study, we designed a novel small-sized positively charged nanofiber-1 (PEI-CNF-1) as a vaccine carrier, which can induce a high long-term humoral immune response by controlled release of antigen. Further studies showed that PEI-CNF-1 could significantly induce the release of immune response factor IL-1 and bone marrow-derived cell (BMDC) maturation. Moreover, compare to other cellulose nanofibers (CNFs), PEI-CNF-1 combined antigen (ovalbumin, OVA) induced and maintained the highest and longest antibody titers after vaccination. Interestingly, the antibody titers have no significant difference between at 21 days and 90 days. Mechanically, we found that PEI-NCF-1 not only could control the slow-release of antigen, but also could be more easily swallowed by macrophages and metabolized by the bodies, thus presenting antigen more effectively. In conclusion, we believe that PEI-CNF-1 have a very high application prospect in inducing long-term humoral immune response, so as to achieve efficient prevention effect to epidemic viruses.
Problem: Recurrent pregnancy loss (RPL) is one of the big challenges of normal pregnancy. Immune dysregulation has been proposed for the key underline mechanisms of RPL. However, the essential roles of T cells, especially γδ T cells, have not been defined. Method of study:Decidua were obtained from normal pregnancy women or recurrent pregnancy loss patients and the surface molecules of γδ T cells in decidua were evaluated via flow cytometric analysis. The expression of PD-1 in clinical samples was analyzed by immunohistochemistry assay. The intracellular cytokines of decidual PD-1 + and PD-1γδ T cells were evaluated by flow cytometric analysis. The cytotoxicity of PD-1γδ T cells were confirmed via an in vitro co-culture experiment. The specific inhibitors for Erk, p38 and JNK against the MAPK pathway were added to the co-culture media to evaluate the functions of the Erk, p38 and JNK. Results:We demonstrated that PD-1 was significantly decreased on decidual tissue γδ T cells of patients with RPL, resulting in the enhanced cytotoxicity of γδ T cells against trophoblasts. We further elucidated an Erk-dependent TNF-α production mediates the γδ T cell cytotoxicity against the trophoblast cells. Finally, the reduced expression of PD-L1 in the villi tissues of patients with RPL might be the cause of the reduction of PD-1 on the tissue γδ T cells.Rong Guo, Silin Jiang, and Jianliang Zhang contribute equally to this work.
Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. The in vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a novel controlled release system based on microbial fermentation for the treatment of IBD.
Background: Overweight affects about 34.3% of Chinese adults, especially women of childbearing age. The purpose of this study was to investigate whether overweight affect the live birth rate of frozen-thawed embryo transfer (FET) cycles in Chinese mothers. Methods: This retrospective case-control study was conducted in all patients undergoing FET cycles from May 2016 to October 2020 at a single center. A total of 969 FET cycles performed in 632 patients were included in the analysis. Patients were divided into the four groups based on the mother’s body mass index (BMI): Group 1: BMI <18.5 kg/m2; Group 2: 18.5 kg/m2 ≤ BMI <24 kg/m2; Group 3: 24 kg/m2 ≤ BMI <28 kg/m2; Group 4: BMI ≥28 kg/m2. The main outcome indicator was the live birth rate per FET cycle. The secondary endpoints included rates of biochemical clinical pregnancy, clinical pregnancy, implantation, multiple pregnancy and miscarriage. Results: Ovarian reserve parameters were similar among the four groups (p = 0.382 for anti-Müllerian hormone and p = 0.195 for antral follicle count). Additionally, the rates of chemical pregnancy, clinical pregnancy, implantation and live birth were comparable in the four groups. Pregnancy outcomes were similar among the four groups using logistic regression analysis adjusting for age, anti-Müllerian hormone (AMH), antral follicle count (AFC), endometrial thickness, indication combined with polycystic ovarian syndrome (PCOS), duration of infertility (years), stage of embryos transferred, previous attempts, protocol of endometrial preparation, number of embryos transferred, and BMI. A decreasing tendency in the rates of clinical pregnancy (p = 0.032) and live birth (p = 0.011) with BMI change was observed through Chi Square for Trend test. Conclusions: Overweight might reduce the possibility of live birth after FET cycles in Chinese mothers.
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