YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway.

Radiotherapy is an important strategy in the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). However, effectiveness of radiotherapy is still restricted by radioresistance. Herein, we aimed to understand the mechanisms underlying ESCC radioresistance, for which we looked into the potential role of YY1. YY1 was upregulated in radioresistant tissues and correlated with poor prognosis of patients with ESCC. YY1 depletion enhanced the radiosensitivity of ESCC in vitro and in vivo. Multi-group sequencing showed that downregulation of YY1 inhibited the transcriptional activity of Kinesin Family Member 3B (KIF3B), which further activated the Hippo signaling pathway by interacting with Integrin-beta1 (ITGB1). Once the Hippo pathway was activated, its main effector, Yes-associated protein 1 (YAP1), was phosphorylated in the cytoplasm and its expression reduced in the nucleus, thus enhancing the radiosensitivity by regulating its targeted genes. Our study provides new insights into the mechanisms underlying ESCC radioresistance and highlights the potential role of YY1 as a therapeutic target for ESCC.

Bushen Qiangjin capsule inhibits the Wnt/α-catenin pathway to ameliorate papain-induced knee osteoarthritis in rat.

OBJECTIVE: To evaluate the molecular mechanism underlying the beneficial effect of Bushen Qiangjin capsule (BSQJ), a Traditional Chinese Medicine, on knee osteoarthritis (KOA). METHODS: In the present study, 32 female Sprague-Dawley rats were randomly divided into four groups: control, KOA, high-dose BSQJ (H-BSQJ), and low-dose BSQJ (L-BSQJ). After successfully establishing the KOA model by intra-articular injection of papain, H-BSQJ and L-BSQJ groups were intragastrically administered 0.243 and 0.122 g/kg BSQJ, respectively, daily for 6 weeks. At the end of the experiment, knee articular cartilage tissues of rats were collected for evaluation by hematoxylin and eosin staining, Safranin O-Fast Green staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Serum interleukin-1α and tumor necrosis factor-α levels of rats were detected with an enzyme-linked immunosorbent assay method. Gene expression of Wnt-4, α-catenin, Frizzled-2, glycogen synthase kinase-3ß (GSK-3ß), cysteinyl aspartate-specific proteinases 3 and 9 (caspases 3 and 9), collagen type II alpha 1 (Col2a1), and matrix metalloproteinases 1 and 13 (MMP-1 and MMP-3) of rat knee articular cartilage was quantified by reverse transcription-quantitative polymerase chain reaction analysis. Wnt-4, α-catenin, Frizzled-2, GSK-3ß, cleaved caspase-3, and cleaved caspase-9 protein expression in rat knee articular cartilage was determined by western blot analysis. RESULTS: BSQJ obviously reduced pathological damage and matrix degradation of articular cartilage in KOA rats. Compared with the KOA group, H-BSQJ rats exhibited downregulated mRNA and protein expression of Wnt-4, ß-catenin, Frizzled-2,and caspase-3, as well as upregulated mRNA and protein expression of GSK-3α. In addition, H-BSQJ significantly increased mRNA expression of Col2a1 and decreased mRNA expression of MMP-1 and MMP-13. CONCLUSION: BSQJ exerted a beneficial effect on KOA by a mechanism involving downregulation of the Wnt/α-catenin pathway, which inhibited both cartilage extracellular matrix degradation and chondrocyte apoptosis to ameliorate KOA in rats.

Effects of bushen qianggu method for primary osteoporosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Primary osteoporosis (POP) is one of the most common orthopedic diseases with a high risk of fracture. Effective treatment of POP is of great significance to reduce the rate of disability and improve the quality of life. Bushen qianggu (BSQG) is a classical method of TCM in treating POP. However, there is no systematic review related to BSQG for POP. The purpose of this study is to provide a comprehensive and reliable evaluation of the clinical evidence of BSQG in the treatment of POP. METHODS AND ANALYSIS: Relevant randomized controlled trial literature evaluating the effect of BSQG on patients with POP will be obtained by searching the PubMed, Embase, MEDLINE, Cochrane Library Central Register of Controlled Trials, China national knowledge infrastructure database, Wan fang database, Chongqing VIP information, and SinoMed from their inception to May 2020. Two researchers will select and evaluate qualified studies independently. The bone mineral density value and the incidence of fractures will be accepted as the primary outcomes. The meta-analyses will be performed by using the RevMan 5.3. RESULTS: This study will provide a comprehensive evaluation of the efficacy and safety of BSQG method for patients with POP. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether BSQG is an effective intervention for patients with POP. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/ZMX3W.

[Influence of Jiangu decoction on peroxisome proliferator-activated receptor (PPAR) in the femoral head of rabbits with steroid-induced femoral head necrosis].

OBJECTIVE: The Jiangu decoction is used in the treatment of steroid-induced femoral head necrosis in clinical experiences, which has functions of tonifying kidney and activating blood, and invigorating spleen to remove phlegm. The decoction is mainly composed of Radix Polygoni Multiflori, Rhizoma alismatis Rhizoma Drynariae, haw, medlar, Radix Astragali, radix rehmanniae, angelica, Radix Codonopsis, radix salviae miltiorrhizae, Fructus Ligustri Lucidi, licorice, pharmaceutical composition. This study was designed to investigate the influence of Jiangu decoction on peroxisome proliferator-activated receptor gamma (PPARgamma) in the femoral head of rabbits with steroid-induced femoral head necrosis. METHODS: Eighteen adult SPF healthy New Zealand rabbits were divided into 3 groups: control group, model group, Jiangu decoction group. The rabbits of Jiangu decoction group orally received Jiangu decoction suspension with a dose of 10 ml/kg each day and the drug content was 0.719 g/ml. The rabbits in control and model groups were given saline with a dose of 10 ml/kg. The methylprednisolone sodium succinate was injected intramuscularly into left leg with a dose of 40 mg/kg. Then the rabbits were fed continuously for 3 weeks. The glucocorticoid levels, PPARgamma and plasma glucocorticoid levels in the femoral head were measured before and after modeling. RESULTS: Before model established, the plasma glucocorticoid levels had no significant difference among three groups (P=0.301). At 3 weeks after model established,the plasma glucocorticoid level of rabbits in model group increased compared to the control group (P=0.001); and the plasma glucocorticoid level of rabbits in Jiangu decoction group decreased compared with model group (P=0.001). The glucocorticoid level in the local femoral head of rabbits in model group increased compared to the control group (P=0.001); and the glucocorticoid level in the local femoral head of rabbits in Jiangu decoction group decreased compared with model group (P=0.001). The PPARgamma level in the local femoral head of rabbits in model group increased compared to the control group (P=0.018);and the PPARgamma level in the local femoral head of rabbits in Jiangu decoction group decreased compared with model group (P=0.033). CONCLUSION: The Jiangu decoction is effective to inhibit the femoral head adipogenic differentiation by decrease the PPAR content, so as to prevent and treat steroid-induced femoral head necrosis.