The present study aimed to examine the effects of isopsoralen against postmenopausal osteoporosis in an ovariectomized rat model. The ovariectomized rats were treated with three days 10 mg/kg isopsoralen or with three days 20 mg/kg isopsoralen. Alkaline phosphatase, the oxidative stress indicators and caspase‑3/9 were measured using ELISA assay kits. Reverse transcription‑quantitative polymerase chain reaction was used to measure collagen type I (Col I), osteocalcin and osteoprotegerin mRNA levels. Wnt, β‑catenin and peroxisome proliferators‑activated receptor γ (PPAR‑γ) were analyzed using western blot analysis. Isopsoralen suppressed mature adipocyte differentiation of C2C12 cells, inhibited serum calcium and urinary calcium levels, and reduced the structural scores of articular cartilage and cancellous bone in the proximal tibia metaphysis of mice with postmenopausal osteoporosis. Isopsoralen also promoted the activity of alkaline phosphatase and the mRNA expression levels of Col 1, osterix and osteopontin in mice with postmenopausal osteoporosis. Oxidative stress and activities of caspase‑3/9 in the mice with postmenopausal osteoporosis were effectively suppressed by isopsoralen treatment, which upregulated the protein expression of Wnt/β‑catenin and downregulated the protein expression of PPAR‑γ. These findings demonstrated that isopsoralen prevented osteoporosis through the regulation of PPAR‑γ/WNT, inhibiting oxidative stress by targeting the PPAR‑γ/WNT pathway. These results provide evidence of the potential targeted therapy for isopsoralen in the clinical treatment of postmenopausal osteoporosis.

ABSTRACT. Peroxisome proliferator-activated receptor is closely associated with the pathogenesis of osteoarthritis. The level of exogenous advanced glycation end-products (AGEs) in articular cartilage is highly associated with the severity of osteoarthritic lesions. However, their interactions and role in promoting osteoarthritisprogression remain unclear. Here, we investigated the effect of AGEs on transforming growth factor (TGF)-β and matrix metalloproteinase (MMP)-9 expression, and discussed the correlation between AGEs and osteoarthritis, possible signaling pathways and mechanism in rabbit chondrocytes. TGF-β and MMP-9 mRNA and protein expression, catalase (CAT) and superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and reactive oxygen species (ROS) levels were analyzed in chondrocytes treated with different concentrations of AGEs using RT-PCR and/or western blot; we detected NF-κB nuclear translocation by immunofluorescence. AGE treatment significantly increased TGF-β and MMP-9 mRNA and protein expression compared to controls (P < 0.01) in a dose-dependent manner (highest at 100 µg/mL). AGE-induced TGF-β and MMP-9 expressions in chondrocytes were significantly inhibited by anti-RAGE and PDTC (0.1 mM) treatment (P < 0.01). Furthermore, AGE-treatment significantly decreased CAT and SOD activity and increased MDA levels in a concentration-dependent manner compared to controls (P < 0.05), significantly promoting NF-κB nuclear translocation. AGE significantly inhibited the increased expression of TGF-β and MMP-9, and induced chondrocyte damage. Its mechanism is associated with RAGE activation, increased ROS expression, and activation of the NF-κB signaling pathways.

Introduction Diabetic foot (DF) is one of the most serious chronic complications of diabetes. In recent years, the use of the tibial cortex transverse transport (TTT) technique has enabled great progress in microcirculation reconstruction and achievement of good outcomes in DF treatment. The objective of this systematic review protocol is to evaluate the efficacy and safety of TTT for DF. Methods Literature search was conducted using the Cochrane Library, Embase, PubMed, Web of Science, China Science Technology Journal Database (VIP), Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Service System (SinoMed), and Chinese Biomedical Literature Service System (CBM) from inception until March, 1st 2022. In addition, our reviewers will retrieve dissertations, grey literature, systematic reviews, and reference lists of the relevant studies. Randomized controlled trials (RCTs) which compared the TTT for DF with conventional treatment will be included. Our reviewers will perform subgroup analysis, sensitivity analysis, and publication bias analysis to evaluate the heterogeneity and robustness. RevMan 5.3 software and Stata V.16.0 software will be used to analyze the available data. Ethics and dissemination Ethical approval was not required because this protocol neither collected private information, nor involved animal experiments. The research was disseminated by academic journals or related meetings. PROSPERO registration number CRD42021279717.

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IntroductionChronic lower extremity angiopathy is a peripheral vascular disease that can result in disability and death. The tibial transverse transport (TTT) technique has been used to treat this disease in recent years. TTT’s effect remains unclear owing to the lack of large samples and high-quality evidence. Therefore, this study aims to assess TTT’s effectiveness and safety in chronic lower extremity angiopathy treatment.Methods and analysisRelevant studies were acquired by searching the following databases: Cochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Science Technology Journal Database (VIP), Wanfang Data and Chinese Biomedical Literature Service System (CBM) until 20 September 2021. All randomised controlled trials and cohort studies on TTT for chronic lower extremity angiopathy will be included in this review. The primary outcomes will include the healing time and healing rate. The additional outcomes will include the Ankle Brachial Index, amputation rate, ankle skin temperature, Visual Analogue Scale, hospitalisation time, vascular endothelial growth factor, effective rate and complications. We will use Stata V.16.0 software and Review Manager V.5.3 software for meta-analysis. Subgroup and sensitivity analyses will be conducted, if necessary.Ethics and disseminationThis study was based on previous data. The medical ethics committee of Inner Mongolia People’s Hospital, located in China waived the need for formal approval of this research, as this study did not fall under the principles of the Declaration of Helsinki. The results will be disseminated through peer-reviewed journals or relevant conferences.PROSPERO registration numberCRD42021281124.