1.The mechanism of Prim-O-glucosylcimifugin in improving cholesterol metabolism in osteoarthritis chondrocytes via lncRNA NEAT1/miR-128-3p
Yanming LIN ; Haishui TU ; Shujie LAN ; Chao LI ; Shiyu LU ; Yue CHEN ; Changlong FU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):55-67
Objective:
To investigate the mechanism of action of Prim-O-glucosylcimifugin (POG) to improve cholesterol metabolism in osteoarthritic (OA) chondrocytes based on the long noncoding RNA nuclear-enriched transcript 1 (lncRNA NEAT1)/microRNA-128-3p (miR-128-3p) pathway.
Methods:
For in vivo experiments, 60 mice were divided into the normal, sham operation, model, and POG groups using the random number table method, with 15 mice per group. The osteoarthritis mouse model was constructed using the modified Hulth method in the model and POG groups. Mice in the POG group were administered 30 mg/(kg·d)POG by gavage. The other groups were administered an equal amount of normal saline for 8 weeks. The cartilage tissue structure of mice in each group was observed using hematoxylin and eosin staining. Real-time PCR was used to detect changes in the lncRNA NEAT1 and miR-128-3p mRNA expression levels in the cartilage tissues of mice. Western blotting was used to detect the protein expressions of ATP-binding cassette transporter A1 (ABCA1), liver X receptor β (LXRβ), matrix metalloprotein-3 (MMP-3), and B-lymphoblastoma-2-associated X protein (Bax) in articular cartilage of mice. An enzyme-linked immunosorbent assay was used to measure the tumor necrosis factor-α (TNF-α) content in the synovial fluid of mice. A biochemical microplate assay was used to measure the total cholesterol level in the synovial fluid of mice. The in vitro experiments were divided into the negative control, interleukin-1β(IL-1β), IL-1β+ POG, IL-1β+ oe-lncRNA NEAT1, IL-1β+ oe-lncRNA NEAT1 + POG, IL-1β + miR-128-3p inhibition, and IL-1β+ miR-128-3p inhibition+ POG groups. An OA model was established by inducing chondrocytes with IL-1β for 24 h, and 90 mg/L of POG and miR-128-3p inhibitor(50 nmol/L) were administered for 48 h as an intervention. lncRNA NEAT1 expression in chondrocytes was detected using fluorescence in situ hybridization. A dual luciferase assay was used to detect the targeting relationship between lncRNA NEAT1 and miR-128-3p. Lentiviral plasmids overexpressing lncRNA NEAT1 were used to transfect mouse chondrocytes. Real-time PCR was used to detect the effect of lncRNA NEAT1 overexpression on the mRNA level of miR-128-3p in chondrocytes. Western blotting was used to detect ABCA1, LXRβ, MMP-3, and Bax protein expression in chondrocytes after lncRNA NEAT1 overexpression and miR-128-3p inhibition.
Results:
POG significantly reduced OA cartilage tissue damage. Compared with the model group, the lncRNA NEAT1 mRNA level decreased, whereas the miR-128-3p mRNA level increased in the cartilage tissue of the POG group (P<0.05). Compared with the model group, ABCA1 and LXRβ protein expression increased in the POG group, whereas MMP-3 and Bax protein expression decreased (P<0.05). The TNF-α levels decreased in the POG group compared to the model group (P<0.05). Compared with the model group, the total cholesterol level in the synovial fluid of the joint of mice in the POG group decreased (P<0.05). The mean fluorescence intensity of lncRNA NEAT1 in the IL-1β+ POG group decreased compared with the IL-1β group (P<0.05). The relative luciferase activity in the miR-128-3p mimics group bound to the lncRNA NEAT1-WT plasmid decreased compared with the miR-128-3p negative control group (P<0.05). The lncRNA NEAT1 mRNA levels decreased, whereas the miR-128-3p mRNA levels increased in the IL-1β+ oe-lncRNA NEAT1 + POG group compared with the IL-1β+ oe-lncRNA NEAT1 group (P<0.05). Compared with the IL-1β+ POG group, ABCA1 and LXRβ protein expression decreased, whereas MMP-3 and Bax protein expression increased (P<0.05).
Conclusion
POG mediates lncRNA NEAT1/miR-128-3p to improve cholesterol metabolism in OA chondrocytes.
2.Clinical Characteristics and Influencing Factors of Rheumatoid Arthritis in Patients with Cold Dampness Obstruction Syndrome
Yanyu CHEN ; Yanqi LI ; Longxiao LIU ; Liubo ZHANG ; Tianyi LAN ; Nan ZHANG ; Cheng XIAO ; Yuan XU ; Qingwen TAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):140-146
ObjectiveTo study the clinical characteristics and influencing factors of rheumatoid arthritis (RA) in the patients with cold dampness obstruction syndrome. MethodsThe RA patients treated in the Department of Traditional Chinese Medicine and Rheumatology of the China-Japan Friendship Hospital from August 2022 to June 2024 were selected. The demographic information, clinical data, laboratory test results, and traditional Chinese medicine (TCM) symptom information were collected for syndrome differentiation, on the basis of which the characteristics and influencing factors of cold dampness obstruction syndrome were analyzed. ResultsA total of 258 RA patients were selected in this study, including 88 (34.1%) patients with cold dampness obstruction syndrome, 53 (20.5%) patients with dampness and heat obstruction syndrome, 31 (12.0%) patients with wind dampness obstruction syndrome, 29 (11.2%) patients with liver-kidney deficiency syndrome, 19 (7.4%) patients with Qi-blood deficiency syndrome, 14 (5.4%) patients with phlegm-stasis obstruction syndrome, 15 (5.8%) patients with stasis obstructing collateral syndrome and 9 (3.5%) patients with Qi-Yin deficiency syndrome. The patients were assigned into two groups of cold dampness obstruction syndrome and other syndromes. The group of cold dampness obstruction syndrome had lower joint fever, 28-tender joint count (TJC28), and 28-joint disease activity score (DAS28)-C-reactive protein (CRP) and higher central sensitization, cold feeling of joints, fear of wind and cold, cold limbs, and abdominal distention than the group of other syndromes (P<0.05). The binary logistic regression analysis showed that central sensitization (OR 5.749, 95%CI 2.116-15.616, P<0.001) and DAS28-CRP (OR 0.600, 95% CI 0.418-0.862, P=0.006) were the independent factors influencing cold dampness obstruction syndrome in RA. ConclusionCold dampness obstruction syndrome is a common syndrome in RA patients. It is associated with central sensitization, cold feeling of joints, abdominal distension and may be a clinical syndrome associated with central sensitization.
3.Research Progress of Traditional Chinese Medicine Intervention in Malignant Tumor Metastasis Based on Metabolic Reprogramming
Hesheng LI ; Chunchan LI ; Huahui GUO ; Jiasheng HUANG ; Congying LAN ; Penghui CHEN ; Renfa HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):272-280
Malignant tumor metastasis is the key factor leading to poor prognosis of patients, and it is a difficult problem to be overcome in the field of tumor therapy. Metabolic reprogramming, as a key link in the regulation of tumor metastasis activity, affects the growth, invasion, and metastasis of tumor cells by changing the metabolic pathways of intracellular substances (such as glucose, amino acids, lipids, and nucleotides). In particular, metabolic reprogramming plays a key role in the multistage linked steps related to tumor metastasis and can play a crucial role in several key stages of tumor tissue dissociation in situ, hematogenous metastasis, and remote colonization. Malignant tumor cells can selectively adjust their own metabolic state to adapt to the growth conditions of different metastatic microenvironments and colonization sites and then choose the most favorable growth and metabolism strategy. According to the holistic concept of traditional Chinese medicine (TCM), the metastasis of malignant tumors is generally closely related to the metabolic state of the whole body. One of the advantages of TCM in the treatment of malignant tumors is systemic regulation. With its multi-pathway, multi-target, and multi-component therapeutic characteristics, TCM can effectively control the metastasis of malignant tumors by regulating the degradation of tumor epithelial mesenchymal transformation (EMT) and extracellular matrix (ECM), anchoring the independent growth of tumor cells and the tumor microenvironment. In this paper, the potential regulatory effects of metabolic reprogramming on the metastasis of malignant tumors were discussed, and the latest research progress of the regulation of metabolic reprogramming by TCM on tumor metastasis was reviewed. At the same time, the key targets of TCM and its bioactive components in the process of tumor metastasis intervention were reviewed. This study aims to provide a more valuable basis and clearer idea for the treatment of malignant tumor metastasis by regulating metabolic reprogramming with TCM.
4.Effects of exercise intervention on intestinal flora in college students:a systematic review
Zhaozhi LIU ; Li HUANG ; Haodong TIAN ; Lan LI ; Xiao CHEN ; Yunfei TAO ; Li PENG
Chinese Journal of Tissue Engineering Research 2025;29(11):2394-2401
BACKGROUND:The regulation of intestinal flora by exercise is closely related to human health,but intestinal flora involves many factors.Existing studies have lacked consistent evidence on the effect of exercise on the intestinal flora of college students. OBJECTIVE:To explore the effects of exercise on intestinal flora diversity and species composition of college students. METHODS:Through systematic search of PubMed,Web of Science,Embase,Medline,Cochrane Library,CNKI,WanFang Database and VIP database,eight empirical studies were selected and included,and semi-quantitative analysis was performed on them. RESULTS AND CONCLUSION:In terms of the species diversity of the intestinal flora,both high-intensity interval training and Tai Chi exercise significantly enhance the species diversity of intestinal flora in college students,while aerobic exercise does not have a significant effect on the enhancement of intestinal flora diversity in college students.In terms of the species composition of the intestinal flora,all three exercise modalities significantly alter the compositional structure of the intestinal flora in college students,which can increase the abundance of beneficial bacteria such as Ruminalococcus,Faecalis prevotelli,Blautia,and decrease the abundance of harmful bacteria such as Escherichia spp.Compared with high-intensity interval training,aerobic and Tai Chi exercise causes more elevated abundance of beneficial bacteria.In addition to changes in intestinal flora characteristics,exercise improves body composition,cardiorespiratory function,and executive function in college students,and these health benefits are closely linked to exercise-induced changes in intestinal flora that can produce health benefits for the body through metabolic regulation,barrier function,and neuromodulation.Although studies have confirmed the association between exercise and intestinal flora,the mechanism by which exercise affects intestinal flora has not yet been clarified,and at the same time,localizing the flora related to the host health is the key to targeting intestinal flora as a therapeutic target in the future,all of which are worthy of further attention and investigation.
5.Application of blood conservation measures with different red blood cell transfusion volumes in obstetrics and their impact on postpartum outcomes
Huimin DENG ; Fengcheng XU ; Meiting LI ; Lan HU ; Xiao WANG ; Shiyu WANG ; Xiaofei YUAN ; Jun ZHENG ; Zehua DONG ; Yuanshan LU ; Shaoheng CHEN
Chinese Journal of Blood Transfusion 2025;38(5):691-698
Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL(OR=1.699)(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma(FFP), cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.
6.Neuroplasticity Mechanisms of Exercise-induced Brain Protection
Li-Juan HOU ; Lan-Qun MAO ; Wei CHEN ; Ke LI ; Xu-Dong ZHAO ; Yin-Hao WANG ; Zi-Zheng YANG ; Tian-He WEI
Progress in Biochemistry and Biophysics 2025;52(6):1435-1452
Neuroscience is a significant frontier discipline within the natural sciences and has become an important interdisciplinary frontier scientific field. Brain is one of the most complex organs in the human body, and its structural and functional analysis is considered the “ultimate frontier” of human self-awareness and exploration of nature. Driven by the strategic layout of “China Brain Project”, Chinese scientists have conducted systematic research focusing on “understanding the brain, simulating the brain, and protecting the brain”. They have made breakthrough progress in areas such as the principles of brain cognition, mechanisms and interventions for brain diseases, brain-like computation, and applications of brain-machine intelligence technology, aiming to enhance brain health through biomedical technology and improve the quality of human life. Due to limited understanding and comprehension of neuroscience, there are still many important unresolved issues in the field of neuroscience, resulting in a lack of effective measures to prevent and protect brain health. Therefore, in addition to actively developing new generation drugs, exploring non pharmacological treatment strategies with better health benefits and higher safety is particularly important. Epidemiological data shows that, exercise is not only an indispensable part of daily life but also an important non-pharmacological approach for protecting brain health and preventing neurodegenerative diseases, forming an emerging research field known as motor neuroscience. Basic research in motor neuroscience primarily focuses on analyzing the dynamic coding mechanisms of neural circuits involved in motor control, breakthroughs in motor neuroscience research depend on the construction of dynamic monitoring systems across temporal and spatial scales. Therefore, high spatiotemporal resolution detection of movement processes and movement-induced changes in brain structure and neural activity signals is an important technical foundation for conducting motor neuroscience research and has developed a set of tools based on traditional neuroscience methods combined with novel motor behavior decoding technologies, providing an innovative technical platform for motor neuroscience research. The protective effect of exercise in neurodegenerative diseases provides broad application prospects for its clinical translation. Applied research in motor neuroscience centers on deciphering the regulatory networks of neuroprotective molecules mediated by exercise. From the perspectives of exercise promoting neurogenesis and regeneration, enhancing synaptic plasticity, modulating neuronal functional activity, and remodeling the molecular homeostasis of the neuronal microenvironment, it aims to improve cognitive function and reduce the incidence of Parkinson’s disease and Alzheimer’s disease. This has also advanced research into the molecular regulatory networks mediating exercise-induced neuroprotection and facilitated the clinical application and promotion of exercise rehabilitation strategies. Multidimensional analysis of exercise-regulated neural plasticity is the theoretical basis for elucidating the brain-protective mechanisms mediated by exercise and developing intervention strategies for neurological diseases. Thus,real-time analysis of different neural signals during active exercise is needed to study the health effects of exercise throughout the entire life cycle and enhance lifelong sports awareness. Therefore, this article will systematically summarize the innovative technological developments in motor neuroscience research, review the mechanisms of neural plasticity that exercise utilizes to protect the brain, and explore the role of exercise in the prevention and treatment of major neurodegenerative diseases. This aims to provide new ideas for future theoretical innovations and clinical applications in the field of exercise-induced brain protection.
7.Evaluation of PEscore performance in predicting platelet transfusion efficacy in hematological patients
Jun LI ; Lan WANG ; Yihua XIE ; Ziqi CHEN ; Gang ZHAO
Chinese Journal of Blood Transfusion 2025;38(6):797-802
Objective: To evaluate the performance of platelet efficacy score (PEscore) in predicting platelet transfusion efficacy in hematological patients. Methods: A total of 485 patients with hematological diseases, including 298 males (62.09±15.45 years) and 187 females (59.17±16.52 years) who received platelet transfusion from January 1, 2021 to December 31, 2024 were enrolled in this study. Clinical data of the patients such as diagnosis, gender, age, number of platelet transfusion, and platelet antibody data were analyzed to investigate the incidence and influencing factors of platelet transfusion refractoriness in hematological patients at our hospital. ROC curve was used to evaluate the performance of PEscore model in predicting platelet transfusion efficacy. The predictive performance of PEscore model was validated by calculating its sensitivity, specificity, and accuracy in 115 clinical cases. Results: The incidence of platelet transfusion refractoriness in 485 cases was 29.90% (145/485). Significant differences (P<0.05) were observed between the effective and ineffective platelet transfusion groups regarding the following factors: diagnosis: lymphoma [55.32% (26/47) vs 44.68% (21/47)], the number of previous platelet transfusions [≥25: 60.78% (31/51) vs 39.22% (20/51)], platelet antibody screening result [positive: 33.76% (53/157) vs 66.24% (104/157)], and platelet transfusion volume (×10
/L) [>6: 62.71% (74/118) vs 37.29% (44/118)]. The area under the ROC curve of PEscore was 0.876. The cut-off points and corresponding sensitivity and specificity were 19.90.59% and 69.44%, respectively. The results of clinical application showed that the sensitivity, specificity and accuracy of the PEscore model for predicting platelet transfusion were 87.50%, 93.41% and 92.17%, respectively. Conclusion: The incidence of platelet transfusion refractoriness in hematological patients is relatively high. PEscore prediction model has a good performance in predicting the effect of platelet transfusion, which can provide a reliable basis for predicting the effect of platelet transfusion in hematological patients before blood transfusion.
8.Effects of fractionated low-dose ionizing radiation on differentially expressed genes in ferroptosis of human bronchial epithelial cells
Min ZHANG ; Lingyu ZHANG ; Yashi CAI ; Huixian LI ; Yanting CHEN ; Guanyou CHEN ; Xin LAN ; Changyong WEN ; Weixu HUANG ; Jianming ZOU ; Huifeng CHEN
Chinese Journal of Radiological Health 2025;34(3):310-317
Objective To investigate the effects of fractionated low-dose ionizing radiation (LDIR) on the ferroptosis in human bronchial epithelial (HBE) cells as well as the associated differentially expressed genes (DEGs), biological processes, and signaling pathways. Methods HBE cells were exposed to different single doses of X-ray irradiation (0, 25, 50, 75, and 100 mGy) for 24, 48, and 72 h, respectively. The change in cell viability was detected by MTT assay. Cells were irradiated with 0, 25, 50, and 100 mGy X-rays 5 times, with 48 h between each irradiation and a dose rate of 50 mGy/min. Cells were harvested 24 h after irradiation for the measurement of the expression of ferroptosis-related genes SLC7A11 and GPX4 at the mRNA and protein levels, cellular iron content, and the expression of FTH1 and FTL mRNAs. High-throughput sequencing was used to screen for the DEGs in each dose group, followed by Gene Ontology-Biological Process (GO-BP) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA). Results Compared with the control group, single-dose LDIR significantly increased cell proliferation at 75 mGy after 24 h (P < 0.05), at 50, 75, and 100 mGy after 48 h (P < 0.05), and at 75 and 100 mGy after 72 h (P < 0.05). Compared with the control group, at the end of the fifth fractionated LDIR, SLC7A11 and GPX4 mRNAs decreased at all doses (P < 0.05), SLC7A11 protein decreased at all doses, GPX4 protein decreased at 25 and 100 mGy, iron content increased at all doses, and FTH1 and FTL mRNAs decreased at all doses (P< 0.05). Sequencing analysis identified 248, 30, and 291 DEGs and 10, 2, and 9 ferroptosis-associated genes at the three doses compared to the control. Gene Ontology-Biological Process analysis showed that DEGs were mainly enriched in biological processes such as response to lipids, cell death, and response to unfolded proteins. Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were mainly enriched in the JAK-STAT signaling pathway, lipids and atherosclerosis, ferroptosis, protein processing in the endoplasmic reticulum, and FoxO signaling pathway. Gene set enrichment analysis showed that DEGs were mainly enriched in ferroptosis, fatty acid degradation, and glutathione metabolism. Conclusion Fractionated low-dose radiation induced ferroptosis in HBE cells, and DEGs were predominantly enriched in biological processes and signaling pathways related to inflammation, ferroptosis, and endoplasmic reticulum stress.
9.Key Information Research and Ancient and Modern Application Analysis of Classic Prescription Houpo Sanwutang
Wenli SHI ; Qing TANG ; Huimin CHEN ; Jialei CAO ; Bingqi WEI ; Lan LIU ; Keke LIU ; Yun ZHANG ; Yujie CHANG ; Yihan LI ; Jingwen LI ; Bingxiang MA ; Lvyuan LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):214-221
Houpo Sanwutang, included in the Catalogue of Ancient Classical Prescriptions (Second Batch), was first recorded in the Synopsis of Golden Chamber written by ZHANG Zhongjing from the Eastern Han dynasty and was modified by successive generations of medical experts. A total of 37 pieces of effective data involving 37 ancient Chinese medical books were retrieved from different databases. Through literature mining, statistical analysis, and data processing, combined with modern articles, this study employed bibliometrics to investigate the historical origin, composition, decoction methods, clinical application, and other key information. The results showed that the medicinal origin of Houpo Sanwutang was clearly documented in classic books. Based on the conversion of the measurements from the Han Dynasty, it is recommended that 110.4 g Magnolia Officinalis Cortex, 55.2 g Rhei Radix et Rhizoma, and 72 g Aurantii Fructus Immaturus should be taken. Magnolia Officinalis Cortex and Aurantii Fructus Immaturus should be decocted with 2 400 mL water first, and 1 000 mL should be taken from the decocted liquid. Following this, Rhei Radix et Rhizoma should be added for further decoction, and then 600 mL should be taken from the decocted liquid. A single dose of administration is 200 mL, and the medication can be stopped when patients restore smooth bowel movement. Houpo Sanwutang has the effect of moving Qi, relieving stuffiness and fullness, removing food stagnation, and regulating bowels. It can be used in treating abdominal distending pain, guarding, constipation, and other diseases with the pathogenesis of stagnated heat and stagnated Qi in the stomach. The above results provide reference for the future development and research of Houpo Sanwutang.
10.Transzonal Projections and Follicular Development Abnormalities in Polycystic Ovary Syndrome
Di CHENG ; Yu-Hua CHEN ; Xia-Ping JIANG ; Lan-Yu LI ; Yi TAN ; Ming LI ; Zhong-Cheng MO
Progress in Biochemistry and Biophysics 2025;52(10):2499-2511
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.


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