Huaifang Li’s research while affiliated with Tongji Hospital and other places

Accelerating wound healing is a main consideration in surgery. The three stages of wound healing are inflammatory response, tissue repair and cell proliferation. Much research has focused on epidermal cell proliferation and migration because this is an essential step in wound healing. The current study discovered that exosomes from Adipose-derived stem cell (ADSC) following hypoxic preconditioning (HExo) have a greater promotional effect on vaginal wound healing. Protein kinase B (AKT)/hypoxia-inducible factor 1-alpha (HIF-1α) play an important role in HExo-mediated HaCaT cell migration and proliferation. The promotional effect of HExo on rat wound healing was reversed by both, HIF‑1α and AKT inhibition. Phosphorylation of AKT (p-AKT) or HIF‑1α suppression reversed the protective effect of HExo on vaginal wound healing. Taken together, our study found that hypoxic preconditioning of adipose MSC exosomes enhances vaginal wound healing via accelerated keratinocyte proliferation and migration through AKT/HIF‑1α axis activation.

The process of endometrial repair after injury involves the synergistic action of various cells including immune cells and stem cells. In this study, after combing Fibrinogen(Fg) with poly(L-lacticacid)-co-poly(ε-caprolactone)(P(LLA-CL)) by electrospinning, we placed Fg/P(LLA-CL) into the uterine cavity of endometrium-injured rats, and bioinformatic analysis revealed that Fg/P(LLA-CL) may affect inflammatory response and stem cell biological behavior. Therefore, we verified that Fg/P(LLA-CL) could inhibit the lipopolysaccharide (LPS)-stimulated macrophages from switching to the pro-inflammatory M1 phenotype in vitro. Moreover, in the rat model of endometrial injury, Fg/P(LLA-CL) effectively promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype and enhanced the presence of mesenchymal stem cells at the injury site. Overall, Fg/P(LLA-CL) exhibits significant influence on macrophage polarization and stem cell behavior in endometrial injury, justifying further exploration for potential therapeutic applications in endometrial and other tissue injuries. Graphical Abstract

While the link between female reproductive function and cardiovascular health (CVH) is well-established, the association between pelvic inflammatory disease (PID) and CVH remains largely unexplored. This study, therefore, sets out to fill this gap in knowledge by investigating the potential relationship between PID and CVH. To ensure the reliability and validity of our findings, data for this cross-sectional study were meticulously collected from the 2015–2018 National Health and Nutrition Examination Survey (NHANES). After applying stringent exclusion criteria, a total of 2442 women were included in the study. The Life Essential 8 (LE8) scoring system, a robust tool developed by the American Heart Association (AHA), was employed to assess the CVH. Logistic regression with multiple variables and smooth curve fitting were utilized to analyze the association. Subgroup and interaction analyses were performed to determine the strength of this association across different demographic groups. The study included 2442 women, with an average CVH score of 66.29 ± 16.27. After accounting for all covariates, each unit increase in CVH score was associated with 2% lower odds of PID prevalence (OR = 0.98, 95% CI: 0.97–0.99). Notably, participants with high CVH had a striking 71% lower odds of PID prevalence compared to those with low CVH. Stratified analyses further revealed a consistent inverse association between CVH score and PID across various subgroups, underscoring the robustness of our findings. The research has uncovered a significant inverse association between CVH and PID. This suggests that improving the CVH level could be a promising strategy for reducing the odds of PID.

Background Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear. Methods We screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS’s function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC. Results We found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes. Conclusion The depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS’s role in regulating angiogenesis and provides a novel target for EC treatment. Supplementary Information The online version contains supplementary material available at 10.1186/s11658-024-00612-7.

(Abstracted from Urogynecology (Phila) 2024;30:138–146 Long-term pelvic floor dysfunction may be caused by pregnancy and childbirth, with urinary incontinence (UI) prevalence rates of 30% in the first 3 postpartum months and persisting in half of those women 20 years after delivery. Combatting pelvic floor dysfunction is possible through pelvic floor muscle training (PFMT), which may improve overall quality of life, as well as prevent UI, sexual dysfunction, and postpartum pelvic muscle impairment.

Background/aim: Chronic pelvic pain (CPP) is a common gynecological condition in women with multifactorial etiology. Some studies have revealed that patients with CPP have the same structural and functional changes in the pain matrix in the brain to patients with other types of chronic pain. However, the relationship between localized pelvic pain and changes in the structure and function of the central nervous system is still unclear. Materials and methods: In this study, a rat model of CPP was established by pelvic nerve ligation and behavioral tests were used to validate the model. Afterwards, we compared the expression of CCL2 in CPP and control rats and observed the changes in their behavioral patterns by blocking the expression of CCL2 in the former group. In addition, we upregulated the expression of CCL2 in human microglia cells (HMC3) to further observe the effect of CCL2 on the Notch2 pathway. Results: Our results showed that the expression of chemokine ligand 2 (CCL2) in the serum exosomes, pelvic vascular endothelial cells, and cerebrospinal fluid was higher in the CPP group than the control group (p<0.05). In HMC3 treated with recombinant CCL2 protein, a significant increase in the mRNA and protein expression of Notch2 was observed. Conclusion: CCL2 can activate the Notch2 signaling pathway and plays an important role in the central sensitization of chronic pelvic pain.

Endometrial damage resulting from surgical procedures is a significant cause of intrauterine adhesion, thin endometrium, and subsequent miscarriage and infertility. Unfortunately, there is currently no effective clinical solution to promote endometrial regeneration after severe injury. In this study, we combined fibrinogen (Fg) and P(LLA‐CL) by electrostatic spinning to form a stable nano‐biomaterial Fg/P(LLA‐CL), which can promote endometrial regeneration. After inducing physical injury to rat endometrium, we found that Fg/P(LLA‐CL) membranes placed in the uterine cavities increased endometrial thickness and the number of glands after injury, while reducing the area of endometrial fibrosis. In addition, Fg/P(LLA‐CL) increased neovascularization and decreased COL1A1 deposition. The expression of TGF‐β1, a cytokine that promotes fibrosis, was down‐regulated in the early stage of injury. Finally, fertility assays confirmed that Fg/P(LLA‐CL) improved the pregnancy rate in rats with endometrial injury, and its safety was verified by blood tests and pathological examination of heart, liver, spleen, lung, and kidney. Therefore, Fg/P(LLA‐CL) shows great potential as a safe and nontoxic biomaterial for endometrial regeneration, ultimately improving pregnancy outcomes in patients with intrauterine adhesion.