Fanghua Gong

1. Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an acute respiratory disorder resulting from sepsis induced by diverse intra- and extrapulmonary factors, including bacteria...

Intrauterine adhesion (IUA), a common gynecological disorder that severely impairs female reproductive health, can cause irreversible damage to patients' fertility. Notably, among patients undergoing surgical treatment, cases of severe intrauterine adhesion not only exhibit a higher postoperative recurrence rate but also present a more prominent tendency toward recurrent miscarriage. Studies have demonstrated that fibroblast growth factor 11 (FGF11) can promote the repair of vascular dysfunction‐related damage. However, its role in IUA remains unclear. Clinical cohort analyses demonstrated that the expression of FGF11 in the serum of IUA patients was significantly upregulated, whereas the expression levels of other FGF11 subfamily members (FGF12, FGF13, and FGF14) exhibited no statistically significant differences, a trend further verified in rat models. Furthermore, FGF11 treatment significantly improved endometrial structure in IUA rats. Fibrosis‐related protein levels (α‐SMA, Collagen I) were markedly decreased, while angiogenesis‐, proliferation‐, and uterine function‐related protein levels (vWF, VEGF‐A, CK19, PCNA, PR, ER) were significantly elevated. Mechanistic studies showed that FGF11 reversed abnormal TGF‐β1/Smad pathway activation in IUA models and promoted the expression of epithelial–mesenchymal transition (EMT)‐related E‐cadherin and N‐cadherin. The TGF‐β1 activator SRI 011381 attenuated FGF11 efficacy and recapitulated TGF‐β1/Smad fibrotic pathway dysregulation. Notably, FGF11 enhanced pregnancy rates in IUA rats. In conclusion, FGF11 ameliorates IUAs and improves reproductive capacity in IUA rats, potentially by inhibiting the TGF‐β1/Smad signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized inflammatory imbalance, intestinal epithelial mucosal damage, and dysbiosis of the gut microbiota. Polygonatum cyrtonema polysaccharides (PCPs) can regulate gut microbiota and inflammation. Here, the different doses of PCPs were administered to dextran sodium sulfate-induced UC mice, and the effects of the whole PCPs were compared with those of the fractionated fractions PCP-1 (19.9 kDa) and PCP-2 (71.6 and 4.2 kDa). Additionally, an antibiotic cocktail was administered to UC mice to deplete the gut microbiota, and PCPs were subsequently administered to elucidate the potential role of the gut microbiota in these mice. The results revealed that PCP treatment significantly optimized the lost weight and shortened colon, restored the balance of inflammation, mitigated oxidative stress, and restored intestinal epithelial mucosal damage. And, the PCPs exhibited superior efficacy in ameliorating these symptoms compared with PCP-1 and PCP-2. However, depletion of the gut microbiota diminished the therapeutic effects of PCPs in UC mice. Furthermore, fecal transplantation from PCP-treated UC mice to new UC-afflicted mice produced therapeutic effects similar to PCP treatment. So, PCPs significantly ameliorated the symptoms, inflammation, oxidative stress, and intestinal mucosal damage in UC mice, and gut microbiota partially mediated these effects.

Background and Purpose: Oat β‐glucan could ameliorate epidermal hyperplasia and accelerate epidermal barrier repair. Dectin‐1 is one of the receptors of β‐glucan and many biological functions of β‐glucan are mediated by Dectin‐1. Dectin‐1 promotes wound healing through regulating the proliferation and migration of skin cells. Thus, this study aimed to investigate the role of oat β‐glucan and Dectin‐1 in epidermal barrier repair.Experimental Approach: To investigate the role of Dectin‐1 in the epidermal barrier, indicators associated with the recovery of a damaged epidermal barrier, including histopathological changes, keratinization, proliferation, apoptosis, differentiation, cell–cell junctions and lipid content were compared between WT and Dectin‐1^−/− mice. Further, the effect of oat β‐glucan on the disruption of the epidermal barrier was also compared between WT and Dectin‐1^−/− mice.Key Results: Dectin‐1 deficiency resulted in delayed recovery and marked keratinization, as well as abnormal levels of keratinocyte differentiation, cell–cell junctions and lipid synthesis during the restoration of the epidermal barrier. Oat β‐glucan significantly reduces epidermal hyperplasia, promotes epidermal differentiation, increases cell–cell junction expression, promotes lipid synthesis and ultimately accelerates the recovery of damaged epidermal barriers via Dectin‐1. Oat β‐glucan could promote CaS receptor expression and activate the PPAR‐γ signalling pathway via Dectin‐1.Conclusion and Implications: Oat β‐glucan promote the recovery of damaged epidermal barriers through promoting epidermal differentiation, increasing the expression of cell–cell junctions and lipid synthesis through Dectin‐1. Dectin‐1 deficiency delay the recovery of epidermal barriers, which indicated that Dectin‐1 may be a potential target in epidermal barrier repair.

The EGFR-RAS-ERK pathway is one of the most important signaling cascades in cell survival, growth, and proliferation. Aberrant activation of this pathway is a common mechanism in various cancers. Here, we report that CDK2 is a novel regulator of the ERK pathway via USP37 deubiquitinase (DUB). Mechanistically, CDK2 phosphorylates USP37, which is required for USP37 DUB activity. Further, USP37 deubiquitinates and stabilizes ERK1/2, thereby enhancing cancer cell proliferation. Thus, CDK2 is able to promote cell proliferation by activating USP37 and, in turn, stabilizing ERK1/2. Importantly, combined CDK1/2 and EGFR inhibitors have a synergetic anticancer effect through the downregulation of ERK1/2 stability and activity. Indeed, our patient-derived xenograft (PDX) results suggest that targeting both ERK1/2 stability and activity kills cancer cells more efficiently even at lower doses of these two inhibitors, which may reduce their associated side effects and indicate a potential new combination strategy for cancer therapy.

Background: Thin endometrium is a reproductive disorder that affects embryo implantation. There are several therapies available for this disease, however they are not so effective. Fibroblast growth factor 1 (FGF1) is a member of fibroblast growth factor superfamily (FGFs), and it has been demonstrated that FGF1 expression was altered in samples collected from patients with thin endometrium. However, it is unclear if FGF1 could improve thin endometrium. The aim of this study was to investigate whether FGF1 have a therapeutic effect on thin endometrium.Methods: A model of thin endometrium induced by ethanol was constructed to investigate the effect and mechanism of action of FGF1 in thin endometrium. In the characterization experiments, 6–8 weeks female rats (n = 40) were divided into four groups: i) Control group; ii) Sham group; iii) Injured group; (iv) FGF1 therapy group. Endometrial tissues would be removed after three sexuel cycles after molding. Morphology and histology of the endometrium were evaluated by visual and hematoxylin and eosin staining. Masson staining and expression of α-SMA in endometrium showed the degree of endometrial fibrosis. Western blotting (PCNA、vWF and Vim) and immunohistochemistry (CK19 and MUC-1) demonstrated the effect of FGF1 on cell proliferation and angiogenesis. Moreover, immunohistochemistry (ER and PR) was used to explore the function of endometrium. The remaining rats (n = 36) were divided into three groups: i) Injured group; ii) FGF1 therapy group; and iii) 3-methyladenine. Western blotting (p38、p-p38、PI3K 、SQSTM1/p62、beclin-1 and LC3) was used to explore the mechanisms of FGF1.Results: In FGF1 therapy group, the morphology and histology of endometrium improved compared with the model group. Masson staining and the expression level of α-SMA showed that FGF1 could decrease the fibrotic area of endometrium. Besides, changes in ER and PR expression in the endometrium suggested that FGF1 could restore endometrium-related functions. Western blotting and immunohistochemistry revealed that PCNA, vWF, Vim, CK19 and MUC-1 were significantly increased after FGF1 treatment compared with the thin endometrium. In addition, Western blotting showed that p38, p-p38, PI3K, SQSTM1/p62, beclin-1 and LC3 levels were higher in FGF1 group than in the injured group.Conclusion: FGF1 application cured the thin endometrium caused by ethanol through autophagy mechanism.