1.Association between snack consumption and depressive symptoms among first year junior high school students with different left behind experiences in Yunnan Province
LIU Na, WU Huijuan, WANG Liangui, LUO Chengyong, CAO Yanrong, FU Yun, ZHANG Tai,〖JZ〗 KONG Jing, HU Mengdie, XIONG Yuan, XU Honglü ;
Chinese Journal of School Health 2026;47(1):18-22
Objective:
To explore the relationship between snack consumption and depressive symptoms in first year junior high school students with different left behind experiences in Yunnan Province, so as to provide a basis for improving depressive symptoms among first year junior high school students with different left behind experiences.
Methods:
From October to December 2022,a cluster random sampling method was used to select 8 500 first year junior high school students from 11 ethnic minority areas (Fugong County, Longling County, Longyang District, Luchun County, Mojiang County, Nanjian County, Qiaojia County, Shuangjiang County, Tengchong City, Yuanmou County, Zhenyuan County) in Yunnan Province for a questionnaire survey. The Chinese version of Depression Anxiety Stress Scale-21 was applied to assess depressive symptoms in first year junior high school students, and snack consumption was collected by employing food frequency questionnaire. The generalized linear model was used to analyze the association between first year junior high school students snack consumption and depressive symptoms, and the analysis was stratified according to left behind experience.
Results:
The detection rates of depressive symptoms among firstyear junior high school students with and without left behind experience were 36.25% and 26.91%, respectively. After controlling for confounding variables, the generalized linear model analysis showed that sweet snacks ( β=0.16, 95%CI =0.07-0.25), fast food ( β=0.14, 95%CI =0.04-0.23) and carbonated drinks ( β=0.09, 95%CI =0.01-0.17) of first year junior high school students with left behind experience (all P <0.05). Compared with those without such behavior, the risk of depressive symptoms was higher in consumption of fast food ( β=0.13, 95%CI =0.07-0.18) and carbonated drinks ( β=0.10, 95%CI =0.06-0.15)among first year junior high school students without left behind experience (both P <0.05).
Conclusion
Snack consumption among first year junior high school students in Yunnan may increase the risk of developing depressive symptoms, while first year junior high school students with left behind experience may have a greater risk of developing depressive symptoms.
2.Cross-cultural adaptation of blood donation behavior intention scale and its reliability and validity test in college students
Yuan CHEN ; Jiao XU ; Jing XIONG ; Jing XU ; Qing ZHANG
Chinese Journal of Blood Transfusion 2026;39(1):83-89
Objective: To translate the common metrics for donation attitude, subjective norm, perceived behavioral control, and intention for the blood donation context (BD-ASPI) into Chinese, and to test its reliability and validity among college students. Methods: A research team was established. Following Beaton's cross-cultural adaptation guidelines, the BD-ASPI was translated, culturally adapted, and pre-tested to develop the Chinese version. Using convenience sampling, 620 students from four universities in Wuhan were surveyed form August to November 2024 to test the scale's reliability and validity. Results: The Chinese version of the scale consisted of 21 items across four dimensions: attitude towards blood donation, subjective norm, perceived behavioral control, and intention. The item-level content validity index ranged from 0.89 to 1.00, and the average scale-level content validity index was 0.984. Confirmatory factor analysis indicated a good fit for the second-order factor model. The Criterion validity was 0.509 (P<0.001). The overall Cronbach's α coefficient was 0.965, with the coefficients for each dimension ranging from 0.891 to 0.974. The test-retest reliability was 0.894. Conclusion: The Chinese version of the BD-ASPI demonstrates good reliability and validity, and can serve as an effective tool for assessing the behavioral intention of voluntary blood donation among college students in China.
3.Association of traditional Chinese medicine syndromes with blood lipid profiles and cardiovascular prognosis in post-percutaneous coronary intervention atherosclerotic cardiovascular disease patients: a prospective cohort study
Huangyu XU ; Qian LI ; Haozhe XIONG ; Weidong HONG ; Xinyi ZHOU ; Xiaoyan LU ; Xiaoli LIU ; Xinrong FAN
Digital Chinese Medicine 2026;9(1):91-102
Objective:
Patients with atherosclerotic cardiovascular disease (ASCVD) following percutaneous coronary intervention (PCI) are classified as very-high-risk individuals in cardiovascular disease (CVD) risk stratification. The distribution pattern of traditional Chinese medicine (TCM) syndromes in this patient population, as well as its association with blood lipid profiles and clinical prognosis, remains unclear. The present prospective cohort study aims to investigate these correlations, thereby providing insights to enrich the research fields.
Methods:
We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1, 2020 and December 31, 2022. Demographics and clinical characteristics, signs and symptoms defining each TCM syndrome, and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events (MACEs). We analyzed the correlation between TCM syndromes, blood lipid profiles, and MACEs, and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression. The analyses were based on detailed baseline and one-year follow-up data.
Results:
A per-protocol analysis was performed on 586 patients with complete data ultimately. During the one-year follow-up, 174 patients (29.69%) experienced a MACE. We performed statistical analyses on comorbidities, medication, and biochemical indicators across groups defined by TCM syndrome differentiation. When comparing different TCM syndromes, no significant differences were found in age, body mass index (BMI), history of revascularization, comorbidities, family history of CVD, smoking or drinking, or statin intensity (P > 0.05). Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol (TC, 5.27 ± 1.18 mmol/L, P < 0.001), triglyceride (TG, 1.96 ± 1.33 mmol/L, P = 0.008), low-density lipoprotein cholesterol (LDL-C, 3.35 ± 0.79 mmol/L, P < 0.001), and high-density lipoprotein cholesterol (HDL-C, 1.24 ± 0.81 mmol/L, P < 0.001) compared with those with other TCM syndromes combined. A multivariable logistic regression model was constructed to predict MACEs. The model included TCM syndrome type [with intertwined phlegm and blood stasis as a predictor, adjusted odds ratio (OR) = 1.413, 95% confidence interval (CI): 0.517 – 3.864, P = 0.501], age (adjusted OR = 0.97, 95% CI: 0.955 – 1.001, P = 0.057), male gender (adjusted OR = 0.698, 95% CI: 0.416 – 1.170, P = 0.173), TC (adjusted OR = 1.004, 95% CI: 0.513 – 1.965, P = 0.990), and LDL-C (adjusted OR = 5.825, 95% CI: 2.214 – 15.326, P < 0.001). This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients [the area under the receiver operating characteristic (ROC) curve (AUC) = 0.865, 95% CI: 0.816 – 0.914].
Conclusion
The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C. The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters (TC and LDL-C) shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI, underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.
4.Effect of Tongbian Decoction (通便汤) on the VAPB-PTPIP51 Complex and Autophagy of Interstitial Cells of Cajal in the Colon of Slow Transit Constipation Model Rats
Chuyue WANG ; Jiacheng LI ; Yingqi YANG ; Sicheng SHEN ; Zhiyang CHEN ; Zhizhong XU ; Bensheng WU ; Meiyao CHEN ; Ziwei XIONG ; Jinhui GU ; Xiaopeng WANG
Journal of Traditional Chinese Medicine 2026;67(9):985-993
ObjectiveTo explore the possible mechanism of Tongbian Decoction (通便汤, TD) in treating slow transit constipation (STC). MethodsTwenty-four SD rats were randomly divided into normal group, model group, TD group, and mosapride group, with 6 rats per group. Except for the normal group, STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment, rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage, while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride, and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration, fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension, the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin (GAS) and motilin (MTL) were measured by ELISA. Colonic histopathology was observed by HE staining, and mucus secretion by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit, stem cell factor (SCF), autophagy-related protein 5 (ATG5), Beclin1, vesicle-associated membrane protein B (VAPB), and protein tyrosine phosphatase interacting protein 51 (VAPB-PTPIP51) were measured by Western Blot, and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF, C-kit, Beclin1, and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group, rats in the model group showed significantly reduced fecal pellet number, fecal water content, small intestinal transit rate, and serum GAS and MTL levels (P<0.01); the number of goblet cells decreased, and the mucosal and muscular layers of the colon became thinner; mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased, while calcium content decreased (P<0.05 or P<0.01); and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group, both TD group and mosapride group showed increased fecal pellet number, fecal water content, small intestinal transit rate, serum GAS and MTL levels, and colonic calcium content, along with decreased Beclin1 and ATG5 protein levels (P<0.05 or P<0.01); the mucosal thickness and goblet cell number increased significantly, and autophagosomes decreased; in the TD group, ATG5 and Beclin1 mRNA levels decreased; in the mosapride group, SCF, VAPB, and PTPIP51 mRNA levels increased, while Beclin1 mRNA decreased (P<0.05 or P<0.01). Compared to the mosapride group, the TD group showed higher fecal pellet number, fecal water content, serum GAS levels, colonic calcium content, and C-kit expression, along with lower ATG5 and Beclin1 levels (P<0.05 or P<0.01). ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions, reducing autophagy of interstitial cells of Cajal, and promoting intestinal motility.
5.Effect of Tongbian Decoction (通便汤) on the VAPB-PTPIP51 Complex and Autophagy of Interstitial Cells of Cajal in the Colon of Slow Transit Constipation Model Rats
Chuyue WANG ; Jiacheng LI ; Yingqi YANG ; Sicheng SHEN ; Zhiyang CHEN ; Zhizhong XU ; Bensheng WU ; Meiyao CHEN ; Ziwei XIONG ; Jinhui GU ; Xiaopeng WANG
Journal of Traditional Chinese Medicine 2026;67(9):985-993
ObjectiveTo explore the possible mechanism of Tongbian Decoction (通便汤, TD) in treating slow transit constipation (STC). MethodsTwenty-four SD rats were randomly divided into normal group, model group, TD group, and mosapride group, with 6 rats per group. Except for the normal group, STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment, rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage, while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride, and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration, fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension, the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin (GAS) and motilin (MTL) were measured by ELISA. Colonic histopathology was observed by HE staining, and mucus secretion by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit, stem cell factor (SCF), autophagy-related protein 5 (ATG5), Beclin1, vesicle-associated membrane protein B (VAPB), and protein tyrosine phosphatase interacting protein 51 (VAPB-PTPIP51) were measured by Western Blot, and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF, C-kit, Beclin1, and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group, rats in the model group showed significantly reduced fecal pellet number, fecal water content, small intestinal transit rate, and serum GAS and MTL levels (P<0.01); the number of goblet cells decreased, and the mucosal and muscular layers of the colon became thinner; mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased, while calcium content decreased (P<0.05 or P<0.01); and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group, both TD group and mosapride group showed increased fecal pellet number, fecal water content, small intestinal transit rate, serum GAS and MTL levels, and colonic calcium content, along with decreased Beclin1 and ATG5 protein levels (P<0.05 or P<0.01); the mucosal thickness and goblet cell number increased significantly, and autophagosomes decreased; in the TD group, ATG5 and Beclin1 mRNA levels decreased; in the mosapride group, SCF, VAPB, and PTPIP51 mRNA levels increased, while Beclin1 mRNA decreased (P<0.05 or P<0.01). Compared to the mosapride group, the TD group showed higher fecal pellet number, fecal water content, serum GAS levels, colonic calcium content, and C-kit expression, along with lower ATG5 and Beclin1 levels (P<0.05 or P<0.01). ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions, reducing autophagy of interstitial cells of Cajal, and promoting intestinal motility.
6.Mechanism of Shenling baizhu san in ameliorating ulcerative colitis via regulating flora metabolism-related proteins and TLR4/NF-κB/NLRP3 inflammatory axis
Jiajia XU ; Yu YOU ; Jiaoman WANG ; Yuhui LIU ; Shiyao CHANG ; Zhixian HE ; Ping LI ; Ziyan WANG ; Wei XIONG ; Fei HAN
China Pharmacy 2026;37(15):1992-1997
OBJECTIVE To investigate the mechanism of Shenling baizhu san (SLBZS) in ameliorating ulcerative colitis (UC). METHODS Mice were randomly divided into normal group, model group, and low-, medium-, high-dose SLBZS groups (3, 6, 12 g/kg), with 10 mice in each group. Except for the normal group, mice in other groups were given free access to 3% dextran sulfate sodium solution for 7 days to establish UC models. Simultaneously, mice in each group were intragastrically administered corresponding medicinal liquid or double-distilled water once a day for consecutive 7 days. After the last administration, the histopathological morphology of colon tissues was observed; the serum levels of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-18 were detected; the total bile acid contents in liver, gallbladder and colon tissues were determined; the expression level of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) in colon tissues was tested. The expression levels of flora metabolism-related proteins [G protein-coupled receptor 41(GPR41),GPR43,farnesoid X receptor (FXR), G protein-coupled bile acid receptor 1 (TGR5), flavin-containing monooxygenase 3 (FMO3), cytochrome P450 family 27 subfamily A member 1 (CYP27A1), CYP7A1] in liver or colon tissues, as well as the proteins related to Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)/NLRP3 inflammatory axis [TLR4, NF-κB, phosphorylated NF-κB (p-NF-κB), myeloid differentiation factor 88 (MyD88), NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1] in colon tissues were measured. RESULTS Compared with the model group, the colon tissue injury and inflammatory cell infiltration were alleviated in medium- and high-dose SLBZS groups. The serum levels of TNF-α, IL-1β and IL-18, total bile acid contents in liver and colon tissues, as well as the protein expression levels of FMO3 and CYP7A1 in liver tissues, TLR4, p-NF-κB, NF-κB, MyD88, NLRP3, ASC and caspase-1 in colon tissues were significantly decreased (P<0.05). Meanwhile, the total bile acid content in gallbladder, the protein expression levels of GPR41 and GPR43 in colon tissues, along with CYP27A1, FXR and TGR5 in liver tissues were significantly increased (P<0.05). CONCLUSIONS SLBZS may relieve colonic inflammatory injury and ameliorate UC by regulating the expression of flora metabolism-related proteins and inhibiting the abnormal activation of TLR4/NF-κB/NLRP3 inflammatory axis.
7.Progress of fecal microbiota transplantation in the treatment of lung cancer
Miao LIU ; Li XIONG ; Shan TAO ; Yi WU ; Weiwei KE ; Yuying LIU ; Yu XU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(09):1495-1500
Lung cancer is one of the most lethal cancers, and the overall survival rate of lung cancer patients is very low. With the increasing research on lung cancer, the critical role of intestinal flora in lung cancer treatment has been gradually discovered. Among the various therapeutic approaches targeting the intestinal flora, fecal microbiota transplantation (FMT) is considered as a potential strategy to treat lung cancer by interfering with the homeostasis of the intestinal flora. FMT can improve the efficacy of lung cancer treatment and attenuate the side effects associated with immunotherapy, chemotherapy, and radiotherapy by remodeling the microbial composition, modulating the metabolites, and activating immune responses. The aim of this paper is to discuss the current status and potential mechanisms of FMT in lung cancer treatment, and to provide a new strategy for regulating the intestinal flora to enhance the prevention and treatment of lung cancer.
8.Analysis of early upper limb function and physical and psychological status in breast cancer patients after different surgeries
Zihan SHAN ; Xiujia LUO ; Shuo XU ; Yimeng GENG ; Xiong WU ; Haoqing JIANG ; Jie JIA
Chinese Journal of Clinical Medicine 2026;33(5):866-871
Objective To explore the effects of breast-conserving surgery (BCS), simple mastectomy (SM), and modified radical mastectomy (MRM) on early postoperative upper limb motor function, physical and psychological status in breast cancer patients. Methods A total of 212 female breast cancer patients undergoing surgery at the Department of Breast Surgery of Zhangzhou Affiliated Hospital of Fujian Medical University from October 2024 to December 2025 were enrolled. Patients were divided into the BCS group (n=34), SM group (n=79), and MRM group (n=99). General demographic and clinical data were collected. At 3–7 days postoperatively, the Constant-Murley score (CMS), active range of motion (AROM) of the shoulder joint, and the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score were used to assess upper limb function; the Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Functional Assessment of Cancer Therapy-Breast (FACT-B), and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate patients’ psychological status, quality of life, and sleep quality. Results The total CMS score, pain score, and range of motion score in the BCS group were higher than those in the SM and MRM groups (P<0.05). The BCS group showed greater forward flexion range of motion than that in the SM and MRM groups (P<0.05); and the SM group showed smaller internal rotation range of motion than that in the MRM and BCS groups (P<0.05). The PHQ-9 depression score in the BCS group was significantly higher than that in the MRM group (P<0.05). There were no statistically significant differences among the three groups in QuickDASH, GAD-7, FACT-B, or PSQI scores. Conclusions Early postoperative upper limb function and depression status varied among breast cancer patients undergoing different surgical procedures. Patients undergoing BCS had better preservation of upper limb function but higher depression scores.
9.Resveratrol Ameliorates Obesity by Targeting NDUFS8/HMGB1 to Promote Adipocyte Browning and Inhibiting Adipose Inflammation
Zedong WANG ; Xianyu XU ; Linlin LI ; Yongping ZHU ; Junzhe ZHANG ; Liwei GU ; Yanqing LIU ; Nan TONG ; Shengnan SHEN ; Yibai XIONG ; Jigang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(23):136-143
ObjectiveTo identify the direct target proteins for the anti-obesity effect of resveratrol (Res) via chemical proteomic analysis and systematically explore the molecular mechanisms by which Res inhibits lipid accumulation in adipocytes from mitochondrial function regulation, adipocyte browning, and inflammation inhibition, thus providing new targets and experimental evidence for the prevention and treatment of obesity and related metabolic diseases. MethodsThe cell counting kit-8 (CCK-8) assay was adopted to detect the safe and effective doses (7.5, 15, 30 μmol·L-1) of Res for treating 3T3-L1 cells based on the cell survival rate. After being induced to differentiate into mature adipocytes, the cells were assigned into the blank [treated with dimethyl sulfoxide (DMSO)] group and the Res (7.5, 15, 30 μmol·L-1) groups and treated for 48 h. Oil red O staining and total triglyceride (TG) content were assessed to measure lipid accumulation in adipocytes. Target protein identification of Res was conducted through IAA-P-based chemical proteomics combined with high-resolution mass spectrometry. Target proteins of Res were validated by cellular thermal shift assay (CETSA) combined with Western blot analysis. Furthermore, the expression of browning markers peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial uncoupling protein 1 (UCP1), as well as the target proteins NADH-ubiquinone oxidoreductase core subunit S8 (NDUFS8) and high-mobility group protein B1 (HMGB1) were determined by Western blot. The ATP assay kit was used to measure the ATP concentration. Mitochondrial biogenesis was characterized with MitoTracker Green, on the basis of which the regulatory effect of Res on mitochondrial function was analyzed. The level of the inflammatory cytokine tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA), on the basis of which the anti-inflammatory effect of Res on adipocytes was evaluated. ResultsCompared with the control group, Res demonstrated safety and efficacy within the range of 7.5-30 μmol·L-1, without significantly affecting cell viability. Compared with the control group, different concentrations of Res reduced lipid accumulation in 3T3-L1 adipocytes (P<0.01), promoted the expression of NDUFS8 (P<0.01), increased the ATP concentration and the protein levels of UCP1 and PGC-1α, elevated the level of TNF-α (P<0.05, P<0.01). ConclusionNDUFS8 and HMGB1were identified as the target proteins of Res in mitigating obesity. Res promotes mitochondrial biogenesis to induce the browning of 3T3-L1 adipocytes via targeting NDUFS8 and it inhibits the TNF-α-mediated inflammatory signaling via targeting HMGB1, thus inhibiting lipid accumulation and ameliorating obesity.
10.LGR5 interacts with HSP90AB1 to mediate enzalutamide resistance by activating the WNT/β-catenin/AR axis in prostate cancer.
Ze GAO ; Zhi XIONG ; Yiran TAO ; Qiong WANG ; Kaixuan GUO ; Kewei XU ; Hai HUANG
Chinese Medical Journal 2025;138(23):3184-3194
BACKGROUND:
Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer.
METHODS:
A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes.
RESULTS:
LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide.
CONCLUSIONS
LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male
;
Humans
;
Phenylthiohydantoin/pharmacology*
;
Benzamides
;
Receptors, G-Protein-Coupled/genetics*
;
Nitriles
;
Cell Line, Tumor
;
HSP90 Heat-Shock Proteins/metabolism*
;
Drug Resistance, Neoplasm/genetics*
;
Prostatic Neoplasms/drug therapy*
;
beta Catenin/metabolism*
;
Receptors, Androgen/genetics*
;
Animals
;
Mice
;
Wnt Signaling Pathway/physiology*


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