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Random-pattern skin flap is widely used in plastic and reconstructive surgery. However, its clinical effect is limited by ischemia necrosis occurs at the distal part of flap. Previous studies have proved that the protective effect of formononetin was associated with its antioxidant, anti-inflammatory ability. However, further research is still needed on the effect of formononetin on flap viability. The purpose of our study was to investigate the effect of formononetin on flap survival and the underlying mechanisms. Two doses (25 mg/kg, 50 mg/kg)of formononetin were administered for seven consecutive days on flap model. Flap tissues were collected on postoperative day 7. Our results revealed that formononetin promoted skin flap viability in a dose-dependent manner. Using immunohistochemical staining and western blot, we found that formononetin significantly reduced oxidative stress and inflammation. Hematoxylin and eosin (H and E) staining, laser Doppler images and immunofluorescence staining showed the enhancement of angiogenesis after formononetin treatment. Mechanistically, we demonstrated that the antioxidation of formononetin was mediated by activation and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2), while down-regulating cytoplasmic Kelch-like ECH-associated protein 1 (Keap1) expression. Co-treatment with formononetin and LY294002 (15 mg/kg), a potent Phosphatidylinositol-3-kinase (PI3K) inhibitor, which aborted nuclear Nrf2 expression and phosphorylated Akt, indicating that formononetin-mediated Nrf2 activation was related to PI3K/Akt pathway. Overall, our findings revealed that formononetin increased angiogenesis, reduced oxidative stress and inflammation, thus promoting flap survival. We highlighted the antioxidant effects of formononetin since the Nrf2 system was activated. Therefore, formononetin might be a promising candidate drug that can enhance survival of skin flaps.

Acute lung injury (ALI) is a life-threatening disease with high incidence and mortality rates. Urolithin A (UA) is a pomegranate intestinal flora metabolite with anti-inflammatory, antioxidant, and anti-aging properties. Ferroptosis is a critical factor in lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the link between UA and ferroptosis is unknown. The purpose of this research was to look into the role of UA in regulating LPS-induced ferroptosis in ALI. The current study used LPS to injure two models, one BEAS-2B cell injury model and one ALI mouse model. UA effectively alleviated LPS-induced ALI compared to the LPS group by lowering in vivo lung wet/dry weight ratio, reactive oxygen species, and malondialdehyde production, as well as superoxide dismutase, catalase, and glutathione depletion. Furthermore, by increasing GPX4 and SLC7A11 expression and decreasing Fe2+ levels, lung histopathological damage, inflammatory cytokine secretion, and ferroptosis levels can be significantly reduced. The Keap1-Nrf2/HO-1 pathway was upregulated by UA, which inhibited LPS-induced ALI and ferroptosis. ML385 inhibited UA’s protective effect against LPS-induced ALI. These findings suggested that UA could be a novel potential therapeutic target for ALI.

Problem: Preeclampsia (PE) is the main factor threatening the life of primipara.Defective migration and invasion of trophoblast cells was one of the causes of PE.Circ_0111277 had been reported to be related to the development of PE, but the mechanism of its effect on trophoblast cells needed further study. Method of Study:The expression of circ_0111277, and grainyhead-like 2 (GRHL2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-20deoxyuridine (EdU) and colony formation assay were used to examine cell proliferation ability. Tube formation and transwell assay were performed to assess the angiogenesis and metastasis ability of cells. Western blot was applied to measure the levels of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and Vimentin) and GRHL2 protein. The relationship between miR-188-3p and circ_0111277 or GRHL2 was verified by the dual luciferase reporter experiment.Results: Circ_0111277 and GRHL2 were elevated, and miR-188-3p was declined in PE patients. Overexpression of circ_0111277 could inhibit the proliferation, angiogenesis, migration, invasion and EMT of trophoblast cells (HTR-8/Svneo). Circ_0111277 was the molecular sponge of miR-188-3p. MiR-188-3p up-regulation could reduce the inhibition of HTR-8/Svneo cell growth caused by overexpression of circ_0111277. GRHL2 was a target gene of miR-188-3p, and GRHL2 silencing relieved the adverse effects of miR-188-3p inhibitors on HTR-8/Svneo. In general, circ_0111277 up-regulated GRHL2 expression through sponge miR-188-3p. Conclusion:Highly expressed circ_0111277 up-regulated the expression of GRHL2 through sponge miR-188-3p, thereby inhibiting trophoblast cells function, which suggested a new molecular mechanism for the pathogenesis of PE.Meixi Zhou and Xiang Yu contributed equally to this work.

Purpose This study aimed to identify risk factors for pulmonary hemorrhage (PH) and higher-grade PH that complicate computed tomography (CT)-guided percutaneous lung biopsy (CT-PNLB) and establish predictive models to quantify the risk. Methods A total of 2653 cases of CT-PNLB were enrolled. Multivariate logistic regression was used to identify independent risk factors to develop a nomogram prediction model. The model was assessed using the area under the curve (AUC) of the receiver operator characteristic (ROC) and calibration curves and validated in the validation group. Results PH occurred in 23.52% (624/2653) of cases, and higher-grade PH occurred in 7.09% (188/2653) of cases. The parameters of lesion size, puncture depth, and contact to pleura were identified as risk factors of PH and higher-grade PH in the logistic regression model, besides the position as a risk factor for PH. The AUC of the PH prediction model was 0.776 [95% confidence interval (CI): 0.752–0.800], whereas that of the validation group was 0.743 (95% CI: 0.706–0.780). The AUC of the higher-grade PH prediction model was 0.782 (95% CI: 0.742–0.832), whereas that of the validation group was 0.769 (95% CI: 0.716–0.822). The calibration curves of the model showed good agreement between the predicted and actual probability in the development and validation groups. Conclusion We identified risk factors associated with PH and higher-grade PH after PNLBs. Furthermore, we developed and validated two risk prediction models for PNLB-related PH and higher-grade PH risk prediction and clinical decision support. Key messages What is already known on this topic Pulmonary hemorrhage (PH) and other hemorrhagic complications are the most common complication in CT-guided percutaneous lung biopsy (CT-PNLB), except pneumothorax. However, the risk factors associated with PH remain controversial, and research on models of PH and higher-grade PH is also limited. What this study adds The parameters of lesion size, puncture depth, and contact to pleura were identified as risk factors of PH and higher-grade PH in the logistic regression model, besides the position as a risk factor for PH. In addition, we developed and validated two risk prediction models for PNLB-related PH and higher-grade PH risk prediction and clinical decision support. How this study might affect research, practice, or policy Of all the predictors, the position is the key factor to be considered by the operator. Moreover, two risk prediction models show good discrimination and calibration characteristics to identify patients at high risk of hemorrhage and higher-grade PH after PNLB, so these could assist clinicians in avoiding risk factors in advance.