1.The Regulatory Effects and Mechanisms of Piezo1 Channel on Chondrocytes and Bone Metabolic Dysregulation in Osteoarthritis
Yan LI ; Tao LIU ; Yu-Biao GU ; Hui-Qing TIAN ; Lei ZHANG ; Bi-Hui BAI ; Zhi-Jun HE ; Wen CHEN ; Jin-Peng LI ; Fei LI
Progress in Biochemistry and Biophysics 2026;53(3):564-576
Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca2+, K+, and Na+, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca2+ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca2+ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca2+ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.
2.Relationship between self-management behaviors and time perspective among patients with comorbid diabetes
YU Dandan ; ZHANG Yaping ; XU Huilin ; HE Dandan ; LIANG Tongtong ; YANG Jiali ; LI Jun
Journal of Preventive Medicine 2025;37(2):130-134
Objective:
To examine the relationship between self-management behaviors and time perspective among patients with comorbid diabetes, so as to provide the evidence for improving self-management behaviors among patients with comorbid diabetes.
Methods:
The patients with comorbid diabetes who were registered in the chronic disease health management system of Minhang District, Shanghai Municipality in 2021, followed up regularly, and lived in Meilong Town were recruited. Demographic information and family history of diabetes were collected through questionnaire surveys. Time perspective and self-management behaviors were assessed using the Zimbardo Time Perspective Inventory and Diabetes Self-Management Behavior Scale, respectively. The relationship between self-management behaviors and time perspective was analyzed using a multivariable ordinal logistic regression model.
Results:
A total of 907 patients with comorbid diabetes were enrolled, including 472 males (52.04%) and 435 females (47.96%). There were 652 cases aged 65 years and above, accounting for 71.89%. In terms of the types of time perspective, 280 patients were future-oriented (30.87%), 236 were balanced (26.02%), 162 were sensation-seeking (17.86%), 123 were fatalistic (13.56%), and 106 were negative (11.69%). In terms of the self-management behaviors, 46 patients were good (5.07%), 643 were moderate (70.89%), and 218 were poor (24.04%). Multivariable ordinal logistic regression analysis showed that after adjusting for age, gender, educational level, marital status, occupation status, monthly income, and family history of diabetes, the patients with comorbid diabetes who had a future-oriented time perspective had better self-management behaviors (OR=1.874, 95%CI: 1.204-2.915).
Conclusion
The self-management behaviors among patients with comorbid diabetes are moderate to poor, and patients with a future-oriented time perspective can better engage in self-management behaviors.
3.The Potential and Challenges of FGF9 as a Cancer Therapeutic Target
Qing ZHANG ; Hong-yan HE ; Jun-hua HUANG ; Xin-yu LU ; Hai-yan LI
Progress in Modern Biomedicine 2025;25(15):2554-2560
Fibroblast growth factor,as a critical protein regulating cell growth and differentiation,exhibits aberrant signaling closely associated with various pathological pathologies,including cancer.Among the members of the fibroblast growth factor family,fibroblast growth factor 9(FGF9)has been identified as a critical player in cancer initiation and progression.While numerous studies have investigated the molecular mechanisms of FGF9 individually,comprehensive reviews addressing its impact in cancer remain scarce.This article systematically reviews the functional mechanisms and regulatory networks of FGF9 in cancer,with a focus on its roles in common malignancies such as lung cancer,liver cancer,gastric cancer,colorectal cancer,breast cancer,and ovarian cancer.The aim is to facilitate translational research on FGF9 for targeted cancer diagnosis and therapy.
4.Treatment and mechanism of chrysoeriol on pulmonary hypertension based on network pharmacology and experimental study
Ying-fang MA ; Meng CAI ; Dan FENG ; Yang GUO ; Yu-he TIAN ; Yun-hua ZHANG ; Li-li WEI ; Yang WANG ; Jun-qiang SI
Chinese Pharmacological Bulletin 2025;41(11):2167-2176
Aim To investigate the effect of chrysoeriol on pulmonary vascular remodeling in pulmonary hyper-tension by animal experiments combined with cell ex-periments,and to explore its potential therapeutic tar-gets by network pharmacology.Methods The target of chrysoeriol was collected in Targetnet,SEA and SwissTargetPrediction database.Pulmonary arterial hy-pertension(PAH)targets were collected in the Dis-GeNET and GeneCards databases,and PPI network map was drawn in the STRING database,and key tar-gets were screened.The GO and KEGG pathway en-richment analysis was carried out through DAVID data-base and Weishengxing platform.AutoDock software was used for molecular docking of key core targets.The PAH model of rats was constructed,and the pulmo-nary hemodynamics and vascular remodeling were de-tected by echocardiography,HE and Masson staining.Primary pulmonary smooth muscle cells were extracted,and the effects of drugs on pathway proteins were de-tected in vitro.Results The results of network phar-macology showed that chrysoeriol exerted therapeutic effects on pulmonary hypertension by affecting key tar-gets such as AKT1,SRC,EGFR,MMP9 and gsk3 β,and signaling pathways such as EGFR and PI3K-AKT.Molecular docking showed that chrysoeriol had good binding ability with 5 key target genes.Animal experi-ments showed that the pulmonary hemodynamic func-tion of PAH rats was significantly improved after ad-ministration of chrysoeriol.The remodeling of small pulmonary arteries was significantly reduced.Cell ex-periments showed that chrysoeriol could inhibit the ex-pression of proliferation,migration and phenotypic transformation genes.Conclusion Chrysoeriol may play a role in the treatment of pulmonary hypertension through multiple targets.
5.Resveratrol protects against oxidative stress damage during sperm cryopreservation by mediating the NRF2 signaling pathway
Lei XIN ; Yutong ZHANG ; Liting LIU ; Jing TAN ; Jingjing ZHANG ; Zongliu DUAN ; Yang GAO ; Jun YANG ; Biao YU ; Qunshan SHEN ; Xiaojin HE
Chinese Journal of Reproduction and Contraception 2025;45(10):1038-1046
Objective:To investigate the protective effects of resveratrol (RSV) on human sperm cryopreservation and explore its underlying protective mechanisms.Methods:A total of 165 normal fresh semen samples were collected from the Reproductive Medicine Center, Department of Obstetrics and Gynecology and Human Sperm Bank of the First Affiliated Hospital of Anhui Medical University between December 2022 and December 2024. Among them, 65 samples were used to obtain semen parameters before and after conventional freezing. Each sample of the other 104 samples was mixed at a 2∶1 volume ratio with cryoprotectant containing 0, 10 -?, 10 -?, or 10 -? mol/L RSV, followed by cryopreservation in liquid nitrogen for 24 h. Post-thaw assessments included routine sperm parameters, sperm DNA fragmentation index (DFI) evaluated by sperm chromatin dispersion assay, reactive oxygen species (ROS) levels measured via flow cytometry, RSV and nuclear factor erythroid 2-related factor 2 (NRF2) interactions examined by molecular docking and cellular thermal shift assay (CETSA), NRF2 protein contents analyzed by immunofluorescence and Western blotting, mRNA levels of NRF2 and downstream antioxidant proteins Heme Oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) quantified by qRT-PCR and effects of NRF2 inhibitor ML385 on sperm parameters. Results:Compared with fresh samples, conventional cryopreservation significantly reduced sperm motility (all P<0.001). The addition of 10 -? mol/L RSV significantly improved the percentage of forward motile sperm after freezing (26.98%±8.98% vs. 19.61%±8.03%, P<0.001) while reducing DFI (9.84%±3.81% vs. 15.06%±4.22%, P<0.001) and ROS levels ( P<0.001) compared with the post-freezing group without the addition of RSV. Both molecular docking analysis and CETSA confirmed that RSV interacted with NRF2. Notably, sperm cryopreserved with 10 -? mol/L RSV exhibited significantly higher contents of NRF2 and its downstream effectors HO-1 and NQO1 compared with the post-freezing group without the addition of RSV (all P<0.001). This protective effect was markedly attenuated by co-treatment with the NRF2 inhibitor ML385, as evidenced by a significant decline in sperm motility ( P<0.001). Conclusion:RSV exerts cryoprotective effects likely through NRF2-mediated antioxidant pathways, reducing oxidative stress and enhancing post-thaw sperm quality.
6.Study on the accuracy of resting full-cycle ratio,quantitative flow ratio,and contrast-induced fractional flow reserve in evaluating coronary artery borderline lesions
Rui-tao ZHANG ; Zhen-yu TIAN ; Li-yun HE ; Lin MI ; Li-jun GUO ; Xin-ye XU
Chinese Journal of Interventional Cardiology 2025;33(3):163-169
Objective To compare the accuracy and clinical application value of contrast-induced fractional flow reserve(cFFR),resting full-cycle ratio(RFR),and quantitative flow ratio(QFR)in evaluating coronary artery borderline lesions,using fractional flow reserve(FFR)as the gold standard.Methods A retrospective study was conducted including 143 patients with 143 lesions who underwent coronary angiography(CAG)and were tested for cFFR,RFR,QFR,and FFR at Peking University Third Hospital from September 2020 to January 2022.Clinical data,CAG lesion anatomical data,and target vessel cFFR,RFR,QFR,and FFR measurements were collected.The correlation and diagnostic concordance of cFFR,RFR,QFR,and FFR were analyzed.Results The mean age of the 143 patients was 66(58,71)years,with 90(62.9%)being male.Among them,60(42.0%)patients were diagnosed with unstable angina,and 115(80.4%)target lesions were located in the left anterior descending artery.Correlation analysis showed that RFR,QFR,and cFFR were all significantly correlated with FFR(r=0.956,r=0.861,r=0.751,P<0.001).Bland-Altman analysis demonstrated high agreement between cFFR,RFR,QFR,and FFR.Receiver operating characteristics(ROC)curve analysis showed that the area under the curve(AUC)for RFR corresponding to FFR ≤0.80 was 0.92(95%CI 0.87-0.96),for QFR was 0.89(95%CI 0.83-0.95),and for cFFR was 0.96(95%CI 0.94-0.99).Conclusions cFFR,RFR,and QFR show high concordance with FFR,with similar diagnostic consistency between the three methods and FFR.
7.Correlation between systemic inflammatory response index and prognosis of elderly patients with heart failure
Jiling YU ; Zhaoyuan ZHANG ; Yifan DENG ; Zhen FANG ; Jun JI ; Shenghu HE ; Jing ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(4):450-453
Objective To explore the correlation between systemic inflammatory response index(SIRI)and the prognosis of elderly heart failure(HF)patients.Methods A retrospective study was conducted on 300 elderly HF patients with complete medical records hospitalized in our de-partment from January to December 2022.During the follow-up period for 1 year in different ways,46 of them were lost,and 254 were finally included.Baseline data,complete blood count at admission,and results of auxiliary examinations,and medicine adherence after discharge were col-lected and recorded.According to the occurrence of major adverse cardiovascular events(MACE),the subjected patients were divided into a MACE group(96 cases)and a non-MACE group(158 cases).The baseline data and relevant examination indicators were compared between the two groups,and the relevant factors for the occurrence were analyzed by using logistic regression.ROC curve analysis was employed to assess the predictive value of SIRI for MACE occurrence.Results The MACE group had significantly advanced age,larger proportion of diabetes mellitus,higher neutrophil and platelet counts,and elevated D-dimer level,but lower standardized medication rate when compared with the non-MACE group(P<0.05,P<0.01).The SIRI level was obviously higher in the MACE group than the non-MACE group[1.70(1.13,2.33)vs 1.29(0.85,2.06),P=0.002].Multivariate logistic regression analysis showed that atrial fibrillation,standardized medi-cation,mononuclear cells,and SIRI were independent risk factors for the occurrence of MACE in elderly HF patients(P<0.05,P<0.01).ROC curve analysis indicated that the AUC value of SIRI in predicting the occurrence of MACE was 0.614(95%CI:0.544-0.683),with a sensitivity of 0.813 and a specificity of 0.437.Conclusion SIRI is significantly correlated with the occurrence of MACE in elderly HF patients,and has a certain predictive value for their prognosis.
8.Comparative study of single-criteria and multi-criteria optimization modes for cervical cancer VMAT radiotherapy plans by Raystation planning system
Gang LI ; Yu-song LONG ; Jun-wen TAN ; Xian-tao HE ; Yong-fu FENG ; Zhan-yu WANG
Chinese Medical Equipment Journal 2025;46(9):39-44
Objective To carry out cervical cancer VMAT radiotherapy planning respectively with the single-criteria optimization(SCO)and multi-criteria optimization(MCO)modes of Raystation 4.7 planning system,and to provide references for selecting optimization mode clinically by comparing and analyzing the dosimetric parameters such as target dose distribution,exposure dose to organ at risk(OAR),monitor unit and beam-on time.Methods Ten cervical cancer patients who attended some hospital from February to December 2022 were retrospectively selected,and some VMAT plans were designed for them with the SCO mode of Raystation 4.7 planning system and then enrolled into a SCO group;other VMAT plans were redesigned with the MCO mode under the premise the setup conditions such as machine model and shot field angle were unchanged,and divided into a MCO group.The two groups were compared in terms of maximum dose(D2%),minimum dose(D98%),homogeneity index(HI)and conformity index(CI)of the planning target volume(PTV),beam-on time,monitor unit and exposure doses to OARs including bladder V50 Gy,V40 Gy and V30 Gy,rectum V50 Gy,V40 Gy and V30 Gy,small intestine V50 Gy,V40 Gy and V30 Gy and left and right femur V50 Gy,V40 Gy and V30 Gy.SPSS 22.0 software was used for statistical analysis.Results Both the two groups met clinical requirements.There were no significant differences between the two groups in D98%,CI,small intestine V50 Gy and left and right femur V40 Gy(P>0.05).The MCO group had the values of HI,D2%,V50 Gy,V40 Gy and V30 Gy,rectum V50 Gy,V40 Gy and V30 Gy,small intestine V40 Gy and V30 Gy and left and right femur V30 Gy lower than those of the SCO group,with the differences being statistically significant(P<0.05).The SCO group had less monitor units and shorter beam-on time when compared with the MCO group,with the differences being statistically siginificant(P<0.05).Conclusion When compared with the SCO mode-based VMAT plans,the MCO mode-based VMAT plans significantly decrease the exposure doses and volume to rectum,bladder and small intestine and raise the PTV homogeneity,while lower the treatment efficiency to some extent by increased monitor units and prolonged beam-on time.[Chinese Medical Equipment Journal,2025,46(9):39-44]
9.Treatment and mechanism of chrysoeriol on pulmonary hypertension based on network pharmacology and experimental study
Ying-fang MA ; Meng CAI ; Dan FENG ; Yang GUO ; Yu-he TIAN ; Yun-hua ZHANG ; Li-li WEI ; Yang WANG ; Jun-qiang SI
Chinese Pharmacological Bulletin 2025;41(11):2167-2176
Aim To investigate the effect of chrysoeriol on pulmonary vascular remodeling in pulmonary hyper-tension by animal experiments combined with cell ex-periments,and to explore its potential therapeutic tar-gets by network pharmacology.Methods The target of chrysoeriol was collected in Targetnet,SEA and SwissTargetPrediction database.Pulmonary arterial hy-pertension(PAH)targets were collected in the Dis-GeNET and GeneCards databases,and PPI network map was drawn in the STRING database,and key tar-gets were screened.The GO and KEGG pathway en-richment analysis was carried out through DAVID data-base and Weishengxing platform.AutoDock software was used for molecular docking of key core targets.The PAH model of rats was constructed,and the pulmo-nary hemodynamics and vascular remodeling were de-tected by echocardiography,HE and Masson staining.Primary pulmonary smooth muscle cells were extracted,and the effects of drugs on pathway proteins were de-tected in vitro.Results The results of network phar-macology showed that chrysoeriol exerted therapeutic effects on pulmonary hypertension by affecting key tar-gets such as AKT1,SRC,EGFR,MMP9 and gsk3 β,and signaling pathways such as EGFR and PI3K-AKT.Molecular docking showed that chrysoeriol had good binding ability with 5 key target genes.Animal experi-ments showed that the pulmonary hemodynamic func-tion of PAH rats was significantly improved after ad-ministration of chrysoeriol.The remodeling of small pulmonary arteries was significantly reduced.Cell ex-periments showed that chrysoeriol could inhibit the ex-pression of proliferation,migration and phenotypic transformation genes.Conclusion Chrysoeriol may play a role in the treatment of pulmonary hypertension through multiple targets.
10.Resveratrol protects against oxidative stress damage during sperm cryopreservation by mediating the NRF2 signaling pathway
Lei XIN ; Yutong ZHANG ; Liting LIU ; Jing TAN ; Jingjing ZHANG ; Zongliu DUAN ; Yang GAO ; Jun YANG ; Biao YU ; Qunshan SHEN ; Xiaojin HE
Chinese Journal of Reproduction and Contraception 2025;45(10):1038-1046
Objective:To investigate the protective effects of resveratrol (RSV) on human sperm cryopreservation and explore its underlying protective mechanisms.Methods:A total of 165 normal fresh semen samples were collected from the Reproductive Medicine Center, Department of Obstetrics and Gynecology and Human Sperm Bank of the First Affiliated Hospital of Anhui Medical University between December 2022 and December 2024. Among them, 65 samples were used to obtain semen parameters before and after conventional freezing. Each sample of the other 104 samples was mixed at a 2∶1 volume ratio with cryoprotectant containing 0, 10 -?, 10 -?, or 10 -? mol/L RSV, followed by cryopreservation in liquid nitrogen for 24 h. Post-thaw assessments included routine sperm parameters, sperm DNA fragmentation index (DFI) evaluated by sperm chromatin dispersion assay, reactive oxygen species (ROS) levels measured via flow cytometry, RSV and nuclear factor erythroid 2-related factor 2 (NRF2) interactions examined by molecular docking and cellular thermal shift assay (CETSA), NRF2 protein contents analyzed by immunofluorescence and Western blotting, mRNA levels of NRF2 and downstream antioxidant proteins Heme Oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) quantified by qRT-PCR and effects of NRF2 inhibitor ML385 on sperm parameters. Results:Compared with fresh samples, conventional cryopreservation significantly reduced sperm motility (all P<0.001). The addition of 10 -? mol/L RSV significantly improved the percentage of forward motile sperm after freezing (26.98%±8.98% vs. 19.61%±8.03%, P<0.001) while reducing DFI (9.84%±3.81% vs. 15.06%±4.22%, P<0.001) and ROS levels ( P<0.001) compared with the post-freezing group without the addition of RSV. Both molecular docking analysis and CETSA confirmed that RSV interacted with NRF2. Notably, sperm cryopreserved with 10 -? mol/L RSV exhibited significantly higher contents of NRF2 and its downstream effectors HO-1 and NQO1 compared with the post-freezing group without the addition of RSV (all P<0.001). This protective effect was markedly attenuated by co-treatment with the NRF2 inhibitor ML385, as evidenced by a significant decline in sperm motility ( P<0.001). Conclusion:RSV exerts cryoprotective effects likely through NRF2-mediated antioxidant pathways, reducing oxidative stress and enhancing post-thaw sperm quality.


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