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08 September 2025, Volume 29 Issue 25 Previous Issue    Next Issue

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Therapeutic effects and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on premature ovarian insufficiency induced by chemotherapy Wei Luxiao, Huang Bingxue, Du Jing, Shi Shuanxia, Wang Jitian, Wang Ling 2025, 29 (25):  5281-5288.  doi: 10.12307/2025.518 Abstract ( 66 )   PDF (2500KB) ( 96 )   Save BACKGROUND: Current research has shown that human umbilical cord mesenchymal stem cells and melatonin can both improve ovarian function. However, the protective effect and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on chemotherapy-induced premature ovarian insufficiency have not been reported. OBJECTIVE: To investigate the protective effect and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on chemotherapy-induced premature ovarian insufficiency. METHODS: Forty Wistar rats with normal estrous cycle were randomly divided into control group, model group, human umbilical cord mesenchymal stem cell group, melatonin group, and human umbilical cord mesenchymal stem cell+melatonin group, with 8 rats in each group. In addition to the control group, the rat model of premature ovarian insufficiency was constructed by intraperitoneal injection of cisplatin solution. The rats in the human umbilical cord mesenchymal stem cell group and the human umbilical cord mesenchymal stem cell+melatonin group were injected with 1×106 human umbilical cord mesenchymal stem cells in the tail vein at 1, 6, and 11 days after modeling, respectively. The rats in the melatonin group and human umbilical cord mesenchymal stem cell+melatonin group were injected intraperitoneally with 10 mg/kg melatonin daily. The changes in body mass and estrous cycle of rats were monitored during treatment. After 14 days of treatment, ELISA was used to detect serum levels of estradiol, follicle stimulating hormone, luteinizing hormone, and anti Mullerian hormone. Ovarian index was calculated. Hematoxylin-eosin staining was performed to observe ovarian histological morphology. Ultrastructure of ovarian granulosa cells was observed by transmission electron microscopy. Western blot assay was conducted to detect the expression of PI3K/AKT/mTOR signaling pathway proteins and LC3 and P62 autophagy proteins in ovarian tissues. RESULTS AND CONCLUSION: (1) Compared with the control group, the body mass of rats in the model group decreased gradually, the estrous cycle was disturbed, and the ovarian index decreased significantly (P < 0.01). The levels of estradiol and anti-Mullerian hormone were decreased (P < 0.01), while the levels of follicle stimulating hormone and luteinizing hormone were increased (P < 0.01). The histological morphology and granulosa cell ultrastructure of ovary were seriously damaged. The protein expressions of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, and P62 were significantly decreased (P < 0.01), while the protein expressions of LC3II/I were significantly increased (P < 0.001). (2) Compared with the model group, the body mass of rats in all treatment groups recovered gradually, the estrous cycle of some rats returned to normal, and the ovarian index was significantly increased (P < 0.01); the levels of estradiol and anti-Mullerian hormone were increased (P < 0.05), while the levels of follicle stimulating hormone and luteinizing hormone were decreased (P < 0.05). The histological morphology and ultrastructure of ovary were significantly improved. The protein expressions of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, and P62 were significantly increased (P < 0.001), while the protein expression of LC3II/I was significantly decreased (P < 0.01). Human umbilical cord mesenchymal stem cell+melatonin group showed more significant improvement in the above indexes. The results suggest that human umbilical cord mesenchymal stem cells combined with melatonin may inhibit ovarian granulosa cell autophagy by upregulating PI3K/AKT/mTOR signaling pathway to treat premature ovarian insufficiency. Figures and Tables | References | Related Articles | Metrics

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Expression of Rab27A in ovarian tissue of polycystic ovary syndrome model mice treated with human umbilical cord mesenchymal stem cells Tao Chenyue, Chen Shuai, Wang Liping, Meng Defang, Zhou Dongjie, Zhou Luojing 2025, 29 (25):  5289-5295.  doi: 10.12307/2025.520 Abstract ( 81 )   PDF (1234KB) ( 146 )   Save BACKGROUND: Polycystic ovary syndrome is a common reproductive endocrine disease leading to infertility in women of reproductive age. Currently, there is no effective treatment. Human umbilical cord mesenchymal stem cells may help to repair ovarian function, but few studies have reported their role in the treatment of polycystic ovary syndrome. OBJECTIVE: To explore the effect and mechanism of human umbilical cord mesenchymal stem cells in the treatment of polycystic ovary syndrome.  METHODS: 3-week-old female ICR mice were divided into three groups (n=15). Normal control group was not treated. Model group was given letrozole for 21 days to induce polycystic ovary syndrome. Treatment group was given letrozole via intragastric administration for 21 consecutive days, and human umbilical cord mesenchymal stem cell suspension was injected through the tail vein. The body weight of mice was monitored before treatment, 7 and 14 days after treatment. The estrous cycle of mice was detected by continuous vaginal smears for 10 consecutive days after treatment. Fourteen days after treatment, peripheral blood sex hormone levels of mice were detected by ELISA. Hematoxylin-eosin staining was used to observe ovarian morphological changes. Immunofluorescence and immunohistochemistry were used to detect the expression of Rab27A protein in ovarian tissues.  RESULTS AND CONCLUSION: (1) Compared with the normal control group, the estrous cycle of mice in the model group was disturbed; body weight was significantly increased; follicle stimulating hormone was decreased; luteinizing hormone and testesterone were both increased; more follicles were found in the ovaries, and the relative expression level of Rab27A protein was decreased. (2) Compared with the model group, the treatment group had diminished body weight, increased follicle stimulating hormone, decreased luteinizing hormone and testesterone, decreased follicles with polycystic dilatation, and increased Rab27A protein relative expression level. (3) These findings suggest that human umbilical cord mesenchymal stem cells improve serum sex hormone levels and ovarian function in polycystic ovary syndrome mice by upregulating the expression of Rab27A. Figures and Tables | References | Related Articles | Metrics

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Mechanism of adipose tissue-derived mesenchymal stem cell-derived exosomes regulating autophagy of hepatic stellate cells Chen Zhenkun, Zhu Shiwei, Xiao Jingnan, Tang Weiping 2025, 29 (25):  5296-5303.  doi: 10.12307/2025.524 Abstract ( 69 )   PDF (2630KB) ( 84 )   Save BACKGROUND: Adipose tissue-derived mesenchymal stem cells release a large amount of exosomes to participate in various pathophysiological processes, but the impact and precise mechanism of exosomes derived from adipose tissue-derived mesenchymal stem cells on autophagy of hepatic stellate cells have not been fully elucidated. OBJECTIVE: To explore the targeted regulatory effect and molecular mechanism of adipose tissue-derived mesenchymal stem cell-derived exosomes on autophagy of hepatic stellate cells through miR-15a-5p.  METHODS: Adipose tissue was collected from inguinal region of 8-week male C57BL/6 mice. Adipose tissue-derived mesenchymal stem cells were extracted by collagenase digestion. Adipose tissue-derived mesenchymal stem cell-derived exosomes were extracted by ultracentrifugation. Mouse liver tissue was obtained, and hepatic stellate cells were isolated and extracted using collagenase perfusion digestion and density gradient centrifugation. The experiment was divided into two groups. In control group, hepatic stellate cells were cultured alone for 48 hours. In the exosome group, hepatic stellate cells were co-cultured with adipose tissue-derived mesenchymal stem cell-derived exosomes for 48 hours. The effects of exosomes on hepatic stellate cell proliferation, activation, autophagy, and expression of fibrosis markers were detected by western blot assay, RT-qPCR, and immunofluorescence staining. RT-qPCR and western blot assay were used to detect the effect of exosomes on the mRNA and protein expression of miR-15a-5p and the downstream signaling pathway Bcl-2, Beclin-1, and Rubicon in hepatic stellate cells.  RESULTS AND CONCLUSION: (1) Compared with the control group, the ratio of autophagy markers LC3-II expression decreased, the number of autophagosome was also significantly decreased, and the intracellular lipid droplets were regenerated, simultaneously, cell volume diminished with the weakening of proliferation in hepatic stellate cells of the exosome group, indicated that the hepatic stellate cell activation was significantly inhibited. (2) Compared with the control group, the expressions of α-smooth actin and type I collagen were significantly decreased (P < 0.01), and the expression of miR-15a-5p was significantly increased in hepatic stellate cells of the exosome group (P < 0.01). At the same time, the expression of its downstream target gene Bcl-2 was significantly decreased (P < 0.01), while the expressions of autophagy genes Beclin-1 and Rubicon were significantly increased in hepatic stellate cells of the exosome group (P < 0.01). The results indicate that adipose tissue-derived mesenchymal stem cell-derived exosomes inhibits the expression of Bcl-2 in hepatic stellate cells by targeting miR-15a-5p and increases the expression of downstream autophagy genes Beclin-1 and Rubicon, thereby inhibiting the autophagy of hepatic stellate cells.   Figures and Tables | References | Related Articles | Metrics

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Effect of culture time in vitro on maturity of induced pluripotent stem cell-derived cardiomyocytes Xiong Tinglin, Zhang Lisha, Wang Dewei, Cao Haiping, Yang Yan 2025, 29 (25):  5304-5310.  doi: 10.12307/2025.517 Abstract ( 124 )   PDF (1708KB) ( 103 )   Save BACKGROUND: It has been proved that induced pluripotent stem cells can differentiate into cardiomyocytes, but there are few reports on the maturity of differentiated cardiomyocytes. OBJECTIVE: To explore the effect of prolonging the induced differentiation time on the morphology, sarcomere length, binuclear cell content, cardiac gene expression, cardiac protein expression, and mitochondrial function of cardiomyocytes derived from induced pluripotent stem cells.    METHODS: Bone morphogenetic protein 4, CHIR 99021, and IWR1 were used to induce pluripotent stem cells to differentiate into cardiomyocytes, and differentiated cardiomyocytes were collected on days 20 and 40 respectively. The expression levels of cardiac genes and proteins in differentiated cardiomyocytes were detected by RT-PCR and immunofluorescence, respectively. LAS X image analysis software was used to analyze the morphology and sarcomere length of differentiated cardiomyocytes. MitoTracker Green FM mitochondrial staining was used to detect total mitochondria. JC-1 mitochondrial staining was used to detect mitochondrial membrane potential.   RESULTS AND CONCLUSION: Differentiated cardiomyocytes on day 40 had longer cell circumference and sarcomere length, and larger cell area than those on day 20 (P < 0.05). The proportion of multinucleated cells rose sharply from about 16% on day 20 to about 29% on day 40 (P < 0.05). Differentiated cardiomyocytes on day 40 had gene expression levels that were more similar to those of the primary cardiomyocytes, and the expression levels of SERCA2A, Cx-43, and α-MHC genes were significantly higher than on day 20 (P < 0.05). Compared with the differentiated cardiomyocytes on day 20, the expression density of TNNT2 and α-MHC protein was relatively higher, the distribution density of mitochondria was larger, and the number of functional mitochondria was greater on day 40 (P < 0.05). The results show that prolonging the induced differentiation time can increase the maturity of differentiated cardiomyocytes by increasing the length of sarcomere and the number of functional mitochondria, as well as improving the expression levels of cardiac genes and proteins. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which hydroxysafflor yellow A alleviates demyelination in cuprizone mice Chen Ying, Liu Jian, Liang Yajie, Li Yanqing, Song Lijuan, Huang Jianjun, Yu Jiezhong, Wang Qing, Ma Cungen 2025, 29 (25):  5311-5319.  doi: 10.12307/2025.519 Abstract ( 74 )   PDF (2156KB) ( 99 )   Save BACKGROUND: In the occurrence and development of demyelinating diseases of the central nervous system, neuroinflammation caused by microglia is the main pathological feature, so inhibiting the inflammatory response is very important to alleviate demyelination. Hydroxysafflor yellow A can protect the blood-brain barrier, inhibit neuronal apoptosis, and improve neurological function. OBJECTIVE: To explore the mechanism of hydroxysafflor yellow A inhibiting bicyclohexanone oxalyl dihydrazone-induced demyelination in mice. METHODS: (1) In vivo: Thirty healthy male C57BL/6 mice were randomly divided into three groups: normal group, cuprizone group, and hydroxysafflor yellow A group. The mice in the cuprizone group and the hydroxysafflor yellow A group were fed with 0.2 % cuprizone diet for 6 weeks to establish mouse models of demyelination. The mice in the normal group were fed with normal diet. At the end of the 4th week, the mice in the hydroxysafflor yellow A group were intraperitoneally injected with hydroxysafflor yellow A 20 mg/kg per day. The mice in the normal and cuprizone groups were intraperitoneally injected with normal saline for 2 weeks. The behavioral changes of mice were evaluated by open field test and elevated plus maze test. The loss of myelin sheath in corpus callosum was detected by black gold staining, myelin basic protein and degraded myelin basic protein immunofluorescence staining. The activation of microglia and the expression of inflammatory factors were detected by Iba-1 immunofluorescence staining and ELISA, respectively. The protein expression levels of Toll-like receptor 4, myeloid differentiation factor 88, and nuclear factor κB p65 in the brain of mice in each group were detected by western blot assay. (2) In vitro experiment: The inflammation model of BV2 microglia was established by lipopolysaccharide induction. BV2 cells were divided into normal group, lipopolysaccharide group (1 μg/mL), and lipopolysaccharide (1 μg/mL) + hydroxysafflor yellow A (25 μmol/L) group. The expression levels of tumor necrosis factor α and interleukin 6 in the supernatant were detected by ELISA.  RESULTS AND CONCLUSION: (1) Compared with the normal group, the mice in the cuprizone group had severe anxiety, abnormal autonomic movement ability, and a large amount of myelin sheath loss in the corpus callosum. The average fluorescence intensity of myelin basic protein was significantly reduced, and the average fluorescence intensity of degraded myelin basic protein was significantly increased. The number of Iba1+ microglia increased, the contents of interleukin 1β, tumor necrosis factor α, and interleukin 6 in the brain increased, and the protein expression levels of Toll-like receptor 4, myeloid differentiation factor 88, and nuclear factor κB p65 increased significantly. The above symptoms and indexes of mice were reversed after hydroxysafflor yellow A treatment. (2) Hydroxysafflor yellow A significantly inhibited the expression of inflammatory factors such as tumor necrosis factor α, and interleukin 6 induced by lipopolysaccharide in BV2 microglia. (3) The above results demonstrate that hydroxysafflor yellow A can significantly improve cuprizone-induced demyelination in mice. The mechanism of action is related to the inhibition of microglial activation-mediated inflammatory response through the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor κB p65 signaling pathway. Figures and Tables | References | Related Articles | Metrics

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M2 macrophage-derived exosomes promote microglia M2-type polarization Fang Jun, Wei Wei, Xue Yating, Cui Chenlong, Wei Jiasheng, Shi Xiao, Yang Lijuan, Yang Baozhong 2025, 29 (25):  5320-5327.  doi: 10.12307/2025.530 Abstract ( 266 )   PDF (1543KB) ( 156 )   Save BACKGROUND: Much of the current research on M2 macrophage-derived exosomes focuses on their effects on wound healing and osteoblast proliferation and differentiation, while few studies have focused on their role in regulating microglia phenotype.  OBJECTIVE: To discuss the role and molecular mechanisms of M2 macrophage-derived exosomes in the phenotypic regulation of microglia. MERHODS: (1) Bone marrow primary macrophages were extracted and then stimulated with 50 ng/mL interleukin 4 for 24 hours to promote macrophage M2-type polarization. Flow cytometry and cellular immunofluorescence were used to identify the M2-type macrophage marker CD206. (2) M2 macrophage-derived exosomes were extracted and identified. (3) Microglia BV2 were randomly divided into three groups: control group, lipopolysaccharide group, and treatment group. No treatment was done in the control group. 500 ng/mL lipopolysaccharide was added to the intervention for 24 hours in the lipopolysaccharide group. 500 ng/mL lipopolysaccharide and 25 μg/mL M2 macrophage-derived exosomes were added simultaneously to the treatment group for 24 hours. ELISA was performed to detect the secretion of tumor necrosis factor α and interleukin 10 in the culture supernatant. qRT-PCR was performed to detect the mRNA expression of inducible nitric oxide synthase, arginase 1, interleukin 1β, and interleukin 10 in the cells. Western blot assay was performed to detect the protein expression of inducible nitric oxide synthase, arginase 1, and nuclear factor-κB signaling pathway related protein expression. RESULTS AND CONCLUSION: (1) ELISA results showed that the secretion of tumor necrosis factor α was significantly increased in the lipopolysaccharide group compared with the control group. The secretion of tumor necrosis factor α was reduced and the secretion of interleukin 10 was increased in the treatment group compared with the lipopolysaccharide group. (2) The qRT-PCR results showed that compared with the control group, the mRNA expression of interleukin 1β and inducible nitric oxide synthase increased in the lipopolysaccharide group. Compared with the lipopolysaccharide group, the mRNA expression of interleukin 1β and inducible nitric oxide synthase decreased, and the mRNA expression of interleukin 10 and arginase 1 increased in the treatment group. (3) Western blot assay results showed that the expression of inducible nitric oxide synthase protein was increased in the lipopolysaccharide group compared with the control group. The expression of inducible nitric oxide synthase protein was decreased and the expression of arginase 1 protein was elevated in the treatment group compared with the lipopolysaccharide group. (4) Compared with the control group, the expression of p65 and p-IκB-α proteins in the nuclear factor-κB signaling pathway was reduced in the lipopolysaccharide group, whereas the expression of p65 and p-IκB-α proteins was elevated in the treatment group compared with the lipopolysaccharide group. The results showed that M2-type macrophage-derived exosomes could significantly inhibit lipopolysaccharide-induced inflammatory responses in microglia, enhance the expression of the anti-inflammatory factor interleukin 10, suppress the expression of the pro-inflammatory factors tumor necrosis factor α and interleukin 1β, and promote microglial cell phenotypes polarized from the M1-type to the M2-type. The mechanism may be related to the inhibition of nuclear factor-κB signaling pathway activation by M2-type macrophage-derived exosomes. Figures and Tables | References | Related Articles | Metrics

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Formononetin inhibits lipopolysaccharide-induced inflammation in nucleus pulposus mesenchymal stem cells Yu Qinghe, Cai Ziming, Tian He, Li Pian, Ruan Ye, Liang Jinzhu, Lin Shuhui, Lin Wenping 2025, 29 (25):  5328-5334.  doi: 10.12307/2025.527 Abstract ( 69 )   PDF (1674KB) ( 191 )   Save BACKGROUND: Formononetin demonstrates potent anti-inflammatory and antioxidant abilities. However, its protective effect on nucleus pulposus mesenchymal stem cells is not yet clear. OBJECTIVE: To investigate the effect and mechanism of formononetin on nucleus pulposus mesenchymal stem cells under an inflammatory microenvironment. METHODS: (1) Primary nucleus pulposus mesenchymal stem cells were isolated from the intervertebral discs of SD rats, and flow cytometry was performed to identify the surface markers of mesenchymal stem cells. (2) The CCK-8 assay was employed to evaluate the impact of lipopolysaccharide and formononetin on the proliferation viability of nucleus pulposus mesenchymal stem cells, aiming to determine the appropriate concentration of formononetin for subsequent cell treatments. (3) An inflammatory microenvironment was simulated by adding 5 μg/mL lipopolysaccharide to the DMEM/F-12 culture medium, and nucleus pulposus mesenchymal stem cells were treated with different concentrations of formononetin for 24 hours. Levels of inflammation markers were detected using western blot assay, real-time quantitative PCR, and immunofluorescence. Western blot assay was conducted to measure the protein levels of the nuclear factor kappa B signaling pathway.  RESULTS AND CONCLUSION: (1) The nucleus pulposus mesenchymal stem cells cultured in adherent wall were shuttle-shaped with good growth status. The results of flow cytometry showed that the surface markers of mesenchymal stem cells were positive for CD29, CD44, and CD90, and the surface markers of hematopoietic stem cells were negative for CD34 and CD45. (2) The treatment with formononetin at 12.5, 25, 50, 100, and 200 μmol/L concentrations for 24 hours had no significant proliferation inhibitory effect on nucleus pulposus mesenchymal stem cells. Compared with the lipopolysaccharide group, the cell viability of nucleus pulposus mesenchymal stem cells treated with 12.5, 25, and 50 μmol/L formononetin for 24 hours was significantly increased, so formononetin at 12.5, 25, and 50 μmol/L concentrations was subsequently selected as the low, medium, and high concentrations for treating nucleus pulposus mesenchymal stem cells. (3) Compared with the lipopolysaccharide group, the protein and mRNA expressions of matrix metalloproteinase-3, matrix metalloproteinase-13, and tumor necrosis factor-α in nucleus pulposus mesenchymal stem cells in the low, medium, and high concentrations of formononetin groups were significantly decreased (P < 0.05) in a dose-dependent manner. (4) Compared with the lipopolysaccharide group, the expressions of phosphorylated nuclear factor kappa B and phosphorylated nuclear factor kappa B inhibitor protein in nucleus pulposus mesenchymal stem cells in the low, medium, and high concentrations of formononetin groups were significantly decreased (P < 0.05) in a dose-dependent manner. The above results suggest that formononetin may attenuate lipopolysaccharide-induced inflammation in rat nucleus pulposus mesenchymal stem cells by inhibiting the activation of the nuclear factor kappa B signaling pathway.  Figures and Tables | References | Related Articles | Metrics

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Aloin mitigates hypoxic injury in rat cardiomyocytes: inhibiting oxidative stress and ferroptosis Tan Mingyue, Jin Yifeng, Zhang Jun, Li Hongxia 2025, 29 (25):  5335-5344.  doi: 10.12307/2025.525 Abstract ( 81 )   PDF (1874KB) ( 176 )   Save BACKGROUND: Myocardial cell hypoxic injury is closely associated with oxidative stress and ferroptosis. Previous studies have shown that aloin has various effects such as antioxidant, anti-inflammatory, and anti-tumor activities. OBJECTIVE: To investigate the effects of aloin on oxidative stress and ferroptosis in hypoxia-induced H9C2 cells. METHODS: A hypoxia model was established using H9C2 myocardial cells. Firstly, cell viability was determined to confirm the lack of cytotoxicity of aloin and to determine its optimal therapeutic concentration. Subsequently, the effects of aloin on hypoxia-induced lactate dehydrogenase release, reactive oxygen species production, and mitochondrial oxidative stress in H9C2 cells were evaluated using assay kits, dihydroethidium fluorescent probes, and MitoSOX™ Red fluorescent probes, respectively. To verify the effect of aloin on ferroptosis, intracellular Fe2+ content and lipid peroxidation level were detected using fluorescence staining and flow cytometry, respectively. Then, the expression levels of ferroptosis regulatory factors glutathione peroxidase 4, acyl-CoA synthetase long-chain family member 4, and nuclear factor E2-related factor 2 were detected using western blot assay and real-time fluorescence quantitative PCR techniques. Finally, the role of ferroptosis in aloin-mediated myocardial protection was further confirmed by using the ferroptosis inducer Erastin. RESULTS AND CONCLUSION: (1) Compared with the control group, the viability of H9C2 cells in the hypoxia group was significantly decreased, lactate dehydrogenase release, reactive oxygen species level, mitochondrial oxidative stress degree, Fe2+ content, and lipid peroxidation degree were significantly increased, while glutathione peroxidase 4 and nuclear factor E2-related factor 2 mRNA and protein expression levels were significantly decreased, and acyl-CoA synthetase long-chain family member 4 mRNA and protein expression were significantly increased (all P < 0.05). (2) Compared with the hypoxia group, both low and high doses of aloin reversed the changes in above indicators (all P < 0.05). (3) Compared with the hypoxia+aloin group, the hypoxia+aloin+Erastin group showed a significant decrease in H9C2 cell viability and a significant increase in lactate dehydrogenase release (both P < 0.01). The results indicate that aloin has a protective effect on hypoxia-treated H9C2 cells in a dose-dependent manner, mainly achieved by inhibiting oxidative stress and ferroptosis. Figures and Tables | References | Related Articles | Metrics

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Feasibility of gastric cancer organoid models for personalized drug screening Fan Hongkai, Guan Yingying, Wang Lumin, Zeng Fanwei, Yin Yirui 2025, 29 (25):  5345-5350.  doi: 10.12307/2025.532 Abstract ( 107 )   PDF (1255KB) ( 126 )   Save BACKGROUND: Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer, but the curative effect of chemotherapy in different patients varies considerably. A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.  OBJECTIVE: To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.  METHODS: The tissue samples of 20 patients with gastric cancer were collected, digested and decomposed, mixed with matrix glue, and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10. Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues. The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin, irinotecan, fluorouracil, oxaliplatin, paclitaxel, and epirubicin.  RESULTS AND CONCLUSION: Fourteen organoids of gastric cancer cases were successfully cultured. There were individual differences in morphology and growth characteristics of organoids. All organoids could be stably passed through, froze and resuscitated. Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues. Six organoids showed different drug sensitivities to six chemotherapy drugs, which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro. Figures and Tables | References | Related Articles | Metrics

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Histone deacetylase 1 gene inhibits pyroptosis of human umbilical vein endothelial cells and alleviates atherosclerosis and inflammatory response Zhang Guoan, Shi Jian, Song Baoguo, Huang Xiaoyan 2025, 29 (25):  5351-5361.  doi: 10.12307/2025.508 Abstract ( 37 )   PDF (2321KB) ( 130 )   Save BACKGROUND: Pyroptosis, as a unique form of inflammatory cell death, plays an important role in the instability of atherosclerotic lesions. OBJECTIVE: To explore the action mechanism of recombinant B-cell lymphoma 2-related protein A1 (BCL2A1) in atherosclerosis.  METHODS: (1) Human umbilical vein endothelial cells were treated with 200 μg/mL oxidized low-density lipoprotein for 24 hours to induce endothelial injury. Subsequently, 50 nmol/L BCL2A1 interfering plasmid (BCL2A1 short hairpin RNA, sh-BCL2A1) and 1.5 μg/mL histone deacetylase 1 gene (HDAC1) overexpression vector (pcDNA-HDAC1) was transfected into human umbilical vein endothelial cells, or both pcDNA-HDAC1 and BCL2A1 overexpression vector (pcDNA-BCL2A1) were transfected simultaneously. After 48 hours of cell culture, the expression levels of BCL2A1 and HDAC1, cell viability, cell pyroptosis level, and BCL2A1 acetylation level were detected. (2) The atherosclerosis mouse model was constructed by high-fat feeding APOE-/- mouse for in vivo verification. 500 μL of BCL2A1 and HDAC1 lentiviral overexpression vectors were injected into mice via tail vein, respectively or simultaneously. The expression levels of BCL2A1 and HDAC1 and the damage of arterial tissue in mice were detected.  RESULTS AND CONCLUSION: The expression of BCL2A1 was upregulated in human umbilical vein endothelial cells induced by oxidized low-density lipoprotein. Interference of BCL2A1 improved cell viability and inhibited pyroptosis and inflammatory response. In addition, HDAC1 was down-regulated in oxidized low-density lipoprotein-induced human umbilical vein endothelial cells. Cell viability was elevated and pyroptosis and inflammatory response were inhibited by promoting BCL2A1 deacetylation. In vivo experiments showed that BCL2A1 was highly expressed in arterial tissues of mice fed with high-fat diet, while HDAC1 was lowly expressed. Additionally, HDAC1 alleviated high-fat diet-induced arterial tissue lesions in ApoE-/- mice by promoting the deacetylation of BCL2A1. It is concluded that HDAC1 may inhibit pyroptosis of human umbilical vein endothelial cells by deacetylating BCL2A1 to reduce atherosclerosis and inflammatory response. Figures and Tables | References | Related Articles | Metrics

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Circular RNA CHACR regulates pressure overload-induced cardiac hypertrophy and oxidative stress damage Wang Shuang, Han Yu, Yuan Min, Cao Jimin, Sun Teng 2025, 29 (25):  5362-5373.  doi: 10.12307/2025.511 Abstract ( 79 )   PDF (2552KB) ( 98 )   Save BACKGROUND: Pathological cardiac hypertrophy is a risk factor for various heart diseases, but its pathogenesis remains unclear. Circular RNAs are strongly associated with cardiac hypertrophy. However, the role of circular RNA CHACR in cardiac hypertrophy and its regulatory mechanisms have not been clarified.  OBJECTIVE: To investigate the role of circular RNA CHACR in pressure overload-induced cardiac hypertrophy and the underlying mechanisms.   METHODS: (1) Transverse aortic constriction was used to induce cardiac hypertrophy in vivo after in situ injection of cyclic RNA CHACR overexpressing lentivirus into the heart for 1 week. Heart mass/tibia length ratio and lung mass/tibia length ratio were calculated; cardiomyocyte surface area was measured; hypertrophic marker gene expression levels were detected; myocardial fibrosis degree was detected, and cardiac function was assessed. (2) H9c2 cardiomyocytes were treated with circular RNA CHACR overexpressing lentivirus for 72 hours, and then treated with 1 µmol/L angiotensin II for 24 hours to induce hypertrophy of cardiomyocytes. The hypertrophy was assessed by measuring the surface area of cardiomyocytes, the expression level of hypertrophic marker genes, and the protein /DNA ratio. Oxidative stress damage was assessed by detecting reactive oxygen species levels and mitochondrial membrane potential.  RESULTS AND CONCLUSION: (1) The expression level of circular RNA CHACR was significantly decreased in both in vivo and in vitro myocardial hypertrophy models (P < 0.01). (2) The overexpression of circular RNA CHACR significantly inhibited the cardiac hypertrophy induced by transverse aortic constriction, including reducing the enlarged heart volume, significantly decreasing the increased heart mass/tibia length ratio (P < 0.05), lung mass/tibia length ratio (P < 0.05), and cardiomyocyte surface area (P < 0.05), and decreasing the upregulated expression levels of hypertrophic markers atrial natriuretic peptide (P < 0.05) and brain natriuretic peptide (P < 0.05). (3) Cardiac fibrosis induced by transverse aortic constriction in mice was significantly inhibited by enforcing expression of circular RNA CHACR, as evidenced by reduced fibrotic area (P < 0.01) and decreased expression levels of the fibrosis marker gene Acta1 (P < 0.05). (4) Overexpression of circular RNA CHACR significantly improved cardiac function in mice, including significantly increased ejection fraction (P < 0.05) and fractional shortening (P < 0.01). (5) Enforced expression of circular RNA CHACR significantly inhibited angiotensin II-induced cardiomyocyte hypertrophy, including a significant reduction in cardiomyocyte surface area (P < 0.05), downregulation of atrial natriuretic peptide (P < 0.05), and brain natriuretic peptide (P < 0.05) expression levels, and a significant decrease in protein/DNA ratio (P < 0.05). (6) Overexpression of circular RNA CHACR significantly inhibited the elevation of reactive oxygen species levels (P < 0.001) and the decrease in mitochondrial membrane potential (P < 0.05) induced by angiotensin II. These results confirm that the expression level of circular RNA CHACR is significantly decreased in cardiac hypertrophy at both in vivo and in vitro myocardial hypertrophy models, and overexpression of circular RNA CHACR significantly inhibits cardiac hypertrophy, alleviates cardiac fibrosis, improves cardiac function, and significantly attenuates angiotensin II-induced oxidative stress damage. Figures and Tables | References | Related Articles | Metrics

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Regulation of THZ1, an inhibitor of cyclin-dependent kinase 7, on stemness of glioma stem cells and its mechanism Hu Enxi, He Wenying, Tao Xiang, Du Peijing, Wang Libin 2025, 29 (25):  5374-5381.  doi: 10.12307/2025.528 Abstract ( 86 )   PDF (1442KB) ( 58 )   Save BACKGROUND: THZ1, an inhibitor of cyclin-dependent kinase 7, has been shown to inhibit the proliferation of a variety of tumor cells, but whether THZ1 can affect the stemness of glioma stem cells through the Wnt/β-catenin signaling pathway remains unclear.  OBJECTIVE: To investigate the effect of THZ1 on stemness of glioma cell U87 and its mechanism.  METHODS: U87 adherent cells were cultured to form stem cell mammospheres. The expressions of stemness related proteins were verified by western blot assay. The effect of THZ1 on half maximal inhibitory concentration (IC50) of U87 cells was determined by Cell Counting Kit-8 (CCK-8) assays. The effects of THZ1 on proliferation and migration of U87 cells were determined by cell colony-formation assays, cell wound healing assays, and Transwell migration assays. The effect of THZ1 treatment on mammosphere forming rate and mammosphere size of U87 stem cells was analyzed. Stemness associated proteins CD133, ABCG2, Nanog, OCT4, SOX2, epithelial-mesenchymal transformation-related proteins E-cadherin, N-cadherin, Occludin, Snail, and Wnt/β-catenin pathway associated proteins Axin1, β-Catenin, WNT-5A, GSK3β, Cyclind-1, and C-myc were measured by western blot assay.  RESULTS AND CONCLUSION: (1) Compared with adherent cells, the expressions of stemness related proteins Nestin, CD133, ABCG2, Nanog, OCT4, and SOX2 were significantly increased. (2) Compared with the control group, THZ1 decreased the proliferation and migration of U87 cells. (3) THZ1 inhibited the mammosphere forming rate and mammosphere size of U87 stem cells. (4) After THZ1 treatment, the expression of N-cadherin and Snail decreased, while the protein expression of E-cadherin and Occludin increased. (5) THZ1 treatment decreased the expression of Wnt/β-catenin pathway related proteins Axin1, β-Catenin, Wnt-5A, GSK3β, Cyclind-1, and C-myc in U87 stem cells. It is concluded that THZ1 can suppress the proliferation and migration of U87 cells, and inhibit the mammosphere forming ability, stemness related protein expression, and epithelial-mesenchymal transformation ability of U87 stem cells by down-regulating the expression of Wnt/β-catenin signaling pathway related molecules. Figures and Tables | References | Related Articles | Metrics

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Protective effect of paeoniflorin on angiotensin II-induced fibrosis in cardiac fibroblasts Ji Yaqiong, Ning Zhongping 2025, 29 (25):  5382-5389.  doi: 10.12307/2025.529 Abstract ( 96 )   PDF (1793KB) ( 75 )   Save BACKGROUND: Previous studies have shown that paeoniflorin has an ameliorative effect on fibrosis in liver and kidney organs, especially in hepatic fibrosis. However, the protective effect of paeoniflorin on angiotensin II-induced fibrosis in cardiac fibroblasts remains unclear. OBJECTIVE: To investigate the protective effects of paeoniflorin on angiotensin II-induced extracellular matrix deposition in cardiac fibroblasts and molecular mechanisms. METHODS: Angiotensin II (1 μmol/L) was added to primary isolated cultured SD rat mammary rat cardiac fibroblasts for 48 hours as the model group. The paeoniflorin low and high dose groups were pretreated with different doses of paeoniflorin (50 and 100 μmol/L) for 2 hours, and then treated with angiotensin II for 48 hours. The SIRT1 inhibitor group was treated with SIRT1 inhibitor EX527 10 μmol/L for 2 hours, followed by paeoniflorin (100 μmol/L) for 2 hours, and then co-incubation with angiotensin II for 48 hours. The cell viability was detected using the cell counting kit-8 method (CCK-8) assay. The cell migration ability was detected by Transwell. The level of intracellular reactive oxygen species was detected by DHA fluorescent probe. The level of oxidative stress markers was detected by relevant kits. Protein expression of fibrosis-related genes was detected by western blot assay. The mRNA expression levels of extracellular matrix and fibrosis-related genes were detected by qRT-PCR. RESULTS AND CONCLUSION: (1) Compared with the control group, the proliferation and migration of cardiac fibroblasts were significantly increased after angiotensin II intervention; the intracellular content of reactive oxygen species and malondialdehyde content were elevated; the activities of superoxide dismutase and catalase were decreased, and the mRNA expression levels of α-smooth muscle actin, type I collagen, type III collagen, fibronectin, connective tissue growth factor, and matrix metalloproteinase 9 were increased. Compared with the model group, paeoniflorin could dose-dependently inhibit the above effect changes (P < 0.01). (2) Compared with the model group, paeoniflorin up-regulated the protein expression of SIRT1 in dose-dependent manner (P < 0.001). (3) Compared with the high-dose paeoniflorin group, the number of cell migration and the expression level of α-smooth muscle actin, type I collagen, and type III collagen were significantly increased in the SIRT1-inhibitor group (P < 0.01). All the experimental results show that paeoniflorin effectively attenuates the angiotensin II-induced changes in cardiac fibroblast fibrosis possibly through up-regulating the expression of SIRT1, dose-dependently inhibits cardiac fibroblast oxidative stress and extracellular matrix deposition, and has a protective effect on cardiac fibroblast fibrosis. Figures and Tables | References | Related Articles | Metrics

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Changes in peripheral blood and bone marrow erythroblasts in rats after hypoxic exposure Xiong Hua, Li Jinjie, Wang Lu, Ma Jie 2025, 29 (25):  5390-5395.  doi: 10.12307/2025.526 Abstract ( 64 )   PDF (958KB) ( 42 )   Save BACKGROUND: The changes in peripheral blood erythrocytes of rats exposed to hypoxia are related to changes in proliferation of erythroblasts in the bone marrow. Related regulatory factors such as hypoxia-inducible factor and erythropoietin are involved. OBJECTIVE: To explore the changes and related factors of peripheral blood erythrocytes and bone marrow erythroblasts in rats after hypoxic exposure. METHODS: An altitude of 5 000 meters was simulated to establish an experimental rat model under a low-pressure and low-oxygen environment. The control group was raised in a laboratory at an altitude of 2 260 meters. The blood routine, bone marrow erythroblast ratio, hypoxia-inducible factor, and erythropoietin of rats were compared before and after hypoxic exposure. RESULTS AND CONCLUSION: (1) The peripheral blood erythrocyte count, hemoglobin, hematocrit and other indicators of the experimental group rats were higher than those of the control group (P < 0.05). (2) The proportion of bone marrow CD71+ erythroblasts of the experimental group rats increased compared with the control group (P < 0.05). (3) The expression level of hypoxia-inducible factor-2α in bone marrow CD71+ erythroblasts of experimental group rats increased compared with the control group (P < 0.05). (4) The erythropoietin level in the bone marrow supernatant of the experimental group rats was higher than that of the control group (P < 0.05). The results indicate that the proportion of peripheral blood erythrocytes and bone marrow erythroblasts in rats increases after hypoxic exposure, which may be related to the increased levels of hypoxia-inducible factor-2α in bone marrow erythroblasts and erythropoietin in bone marrow supernatant. Figures and Tables | References | Related Articles | Metrics

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Angiopoietin-like protein 4 affects progression of diabetic foot by regulating fibroblast and endothelial cell functions Song Qinghong, Wu Nan, Shi Yan, Cui Hongyu, Liu Fei, Liu Hanchong, Zhou Ning, Yao Bin 2025, 29 (25):  5396-5402.  doi: 10.12307/2025.516 Abstract ( 65 )   PDF (1526KB) ( 69 )   Save BACKGROUND: Studies have shown that vascular factors have an important impact on the occurrence of diabetic foot. OBJECTIVE: To investigate the important role of angiopoietin-like protein 4 in the formation of diabetic foot. METHODS: (1) Bioinformatics analysis was performed on the gene expression profile data of diabetic foot patients to find the key genes. The skin samples of diabetic foot patients and healthy people were collected for hematoxylin-eosin staining, immunohistochemical staining, and qRT-PCR experiments to detect the expression of angiopoietin-like protein 4. (2) The immortalized human skin fibroblast cell line and primary human umbilical vein endothelial cells were cultured. The two kinds of cells were divided into control group and exogenous angiopoietin-like protein 4 supplemented group. The migration ability and proliferation ability of fibroblasts were detected by scratch assay and CCK-8 assay. The proliferation ability of endothelial cells was detected by Ki67 assay. RESULTS AND CONCLUSION: (1) Bioinformatics analysis results showed that the down-regulation of angiopoietin-like protein 4 gene might be the key gene leading to the formation of diabetic foot. (2) Hematoxylin-eosin staining exhibited that compared with normal skin, angiopoietin-like protein 4 was weakly expressed in diabetic foot skin, and the mRNA level was decreased (P < 0.01). (3) Scratch assay results demonstrated that compared with the control group, fibroblast migration ability was significantly enhanced in the angiopoietin-like protein 4 group. CCK-8 assay showed that the absorbance value of fibroblasts in the angiopoietin-like protein 4 group was higher than that of the control group at 24 and 48 hours (P < 0.01, P < 0.001). It is suggested that angiopoietin-like protein 4 can enhance the migration and proliferation of fibroblasts. (4) Ki67 assay results demonstrated that the number of Ki67 positive cells in the angiopoietin-like protein 4 group was significantly more than that in the control group. CCK-8 assay results showed that the absorbance value of endothelial cells in the angiopoietin-like protein 4 group was higher than that of the control group at 24 and 48 hours (P < 0.05, P < 0.001). (5) All findings suggest that angiopoietin-like protein 4 can enhance the proliferation of endothelial cells treated with high glucose. Figures and Tables | References | Related Articles | Metrics

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Coiled-coil-helix-coiled-coil-helix domain-containing 2 inhibits apoptosis of Parkinson’ s disease SH-SY5Y cells by promoting mitochondrial autophagy Zhu Liuhui, Zhang Xinyue, Zhu Zhouhai, Yang Xinglong, Guan Ying, Liu Bin 2025, 29 (25):  5403-5413.  doi: 10.12307/2025.098 Abstract ( 135 )   PDF (2546KB) ( 195 )   Save BACKGROUND: Whether coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) can regulate the neuroprotective role of PINK1/Parkin-mediated mitochondrial autophagy in Parkinson’s disease remains unknown. OBJECTIVE: To explore the role and mechanisms of CHCHD2 in the 6-hydroxydopamine-induced Parkinson’s disease cell model in mediating the PINK1/Parkin signaling pathway and its involvement in mitochondrial autophagy. METHODS: Utilizing recombinant plasmid transfection technology to overexpress or knockdown CHCHD2, SH-SY5Y cells were constructed with a Parkinson’s disease model using 6-hydroxydopamine, and divided into control group, model group, overexpression negative control+6-hydroxydopamine group, knockdown negative control+6-hydroxydopamine group, overexpression CHCHD2+6-hydroxydopamine group, and knockdown CHCHD2+6-hydroxydopamine group. Western blot assay and RT-qPCR were used to detect CHCHD2 expression. Western blot assay was utilized to detect the protein expression of LC3I/II, p62, MFN1, COXIV, DRP1, PINK1, Parkin, TIM23, Bax, Bcl-2, and cleaved-caspase 3. CCK-8 assay, JC-1, and reactive oxygen species assay kits were used to measure cell viability, mitochondrial membrane potential, and reactive oxygen levels. Monodansylcadaverine staining was used to observe cell autophagy. Transmission electron microscopy was used to observe autophagolysosomes. RESULTS AND CONCLUSION: (1) Compared with the control group, cell activity, mitochondrial membrane potential, and the protein expression levels of CHCHD2, PINK1, and Parkin were decreased, and the levels of reactive oxygen species, apoptosis, and LC3I/II and p62 proteins were increased (P < 0.05), and the presence of autophagic lysosomes was observed in the model group. (2) Compared with the model group, overexpression of CHCHD2 could reduce the level of cellular reactive oxygen species, increase the mitochondrial membrane potential, and the expression levels of PINK1, Parkin, and MFN1 proteins, and observed an increase in mitochondrial autolysosomes, and the knockdown of CHCHD2 had the opposite effect with the increase of COXIV, TIM23 and p-DRP1 protein expression (P < 0.05). (3) Compared with the model group, overexpression of CHCHD2 reduced apoptosis, up-regulated Bcl-2, and down-regulated the expression of Bax and cleaved-caspase3 proteins, while knockdown of CHCHD2 had the opposite effect (P < 0.05). (4) The results suggest that CHCHD2 can play a neuroprotective role by promoting PINK1/Parkin-mediated mitochondrial autophagy, improving mitochondrial function, and alleviating apoptosis in 6-hydroxydopamine-induced Parkinson’s disease cell models. Figures and Tables | References | Related Articles | Metrics

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Action mechanism and progress of stem cells against ovarian granulosa cell senescence Lin Meiyu, Zhao Xilong, Gao Jing, Zhao Jing, Ruan Guangping 2025, 29 (25):  5414-5421.  doi: 10.12307/2025.521 Abstract ( 149 )   PDF (1153KB) ( 257 )   Save BACKGROUND: As an emerging treatment method, stem cell therapy is expected to improve the ovarian environment, delays the aging of ovarian granulosa cells, and brings new hope to older pregnant women. OBJECTIVE: To review the mechanism and research progress of stem cells against ovarian granulosa cell senescence. METHODS: CNKI and PubMed databases were retrieved for articles on stem cell therapy for ovarian granulosa cell senescence. Chinese and English search terms were “stem cells, ovary granulosa cells, aging.” Finally, 67 articles were included for analysis.  RESULTS AND CONCLUSION: (1) This review summarizes five mechanisms of ovarian granulosa cell senescence: DNA damage and decreased repair capacity, oxidative stress, impaired mitochondrial function, inflammatory response, and changes in hormone levels. (2) This article summarizes five main mechanisms of stem cells in the treatment of ovarian granulosa cell senescence: promoting proliferation and inhibiting apoptosis, differentiation potential and regeneration ability, secreting factors, anti-oxidation, anti-inflammatory response, and immune regulation. (3) At present, there are various types of stem cells that can cooperate to treat ovarian granulosa cell senescence through a variety of ways, and stem cell therapy has broad prospects in restoring female fertility. Figures and Tables | References | Related Articles | Metrics

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Effect of stromal cell-derived factor-1 in cartilage and subchondral bone homeostasis Liang Zhifeng, Yang Yingcai, Cheng Qiangang, Jia Yongxing, Wang Bo 2025, 29 (25):  5422-5433.  doi: 10.12307/2025.504 Abstract ( 39 )   PDF (2148KB) ( 173 )   Save BACKGROUND: Osteoarthritis is a degenerative disease characterized by cartilage degeneration and abnormal bone remodeling of subchondral bone. In recent years, many studies have shown that stromal cell diffracting factor-1 plays a key role in the pathological progression of osteoarthritis. Targeted regulation of stromal cell-derived factor-1 and its CXC chemokine receptor 4 and CXC chemokine receptor 7 signaling pathways is a new method for prevention and treatment of osteoarthritis. OBJECTIVE: To review the role of stromal derived factor-1 in regulating the proliferation, differentiation, and apoptosis of chondrocytes, bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts, as well as explore the mechanism by which the interaction of these cells leads to cartilage degeneration and abnormal bone remodeling of subchondral bone and accelerates the pathological progression of osteoarthritis, in order to provide new ideas for the prevention and treatment of osteoarthritis. METHODS: CNKI, WanFang Data, and VIP, were searched with Chinese search terms “stromal cell-derived factor 1, cartilage, chondrocytes, subchondral bone, bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, CXC chemokine receptor 4, CXC chemokine receptor 7.” PubMed, Medline, and Embase databases were searched with English search terms “stromal cell-derived factor 1, SDF-1, CXCL12, cartilage, chondrocyte, subchondral bone, mesenchymal stem cells, osteoblasts, osteoclasts, CXCR4, CXCR7.” Literature retrieval time was from inception to January 2024. A total of 77 articles were included and summarized in accordance with the inclusion and exclusion criteria. RESULTS AND CONCLUSION: (1) Stromal cell-derived factor-1 regulates the migration, proliferation, differentiation, and death of chondrocytes, bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts, which plays an important role in maintaining cartilage and subchondral bone homeostasis, promoting or inhibiting cartilage degeneration and abnormal bone remodeling in osteoarthritis. Targeted regulation of stromal cell-derived factor-1/CXC chemokine receptor type 4 / CXC chemokine receptor type 7 signaling pathway is expected to become the focus of future research on the prevention and treatment of osteoarthritis. (2) Because of the difference in the expression of stromal cell-derived factor-1 subtypes in tissues, stromal cell-derived factor-1 α is the most widely studied at present. The related studies of stromal cell-derived factor-1β and stromal cell-derived factor-1γ are mainly focused on exploring the effects on the biological behavior of stem cells, the role in the regulation of cartilage and subchondral bone homeostasis, and the correlation with osteoarthritis. (3) Stromal cell-derived factor-1 can effectively promote stem cells homing to cartilage injury sites, and induce their proliferation, survival, and cartilage differentiation. The application of stromal cell-derived factor-1-loaded biological scaffolds to improve the quality of cartilage repair has become the focus of cartilage tissue engineering research. However, previous studies have shown that stromal cell-derived factor-1 can promote the differentiation of bone marrow mesenchymal stem cells into hypertrophic chondrocytes, while the hypertrophic phenotype of newborn chondrocytes can lead to endochondral bone formation and chondrocyte apoptosis. The whole tissue is vascularized and ossified, which affects the quality of cartilage repair. In addition, when different scaffolds combined with stromal cell-derived factor-1 can repair partial cartilage injury and full-thickness cartilage injury, the regenerated tissue is not all ideal hyaline cartilage tissue. Therefore, in the future, in-depth exploration of the potential mechanism of stromal cell-derived factor-1 in stem cell biological effects and the best combination of stromal cell-derived factor-1 and scaffold in repairing different cartilage defects will help to improve the quality of cartilage repair. (4) The studies on CXC chemokine receptor 4 antagonists are mainly focused on AMD3100, T140 and TN14003, and most of them are in the basic experimental stage and need to be transformed into clinical practice. The safety and effectiveness of the therapeutic drugs developed for stromal cell-derived factor-1/CXC chemokine receptor 4 / CXC chemokine receptor 7 signaling pathway still need a large number of biological and clinical trials to support. Figures and Tables | References | Related Articles | Metrics

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Role of different cell-derived exosomal miRNAs in progression, diagnosis, and prognosis of gastric cancer Wang Lei, Wang Baiyan, Zhou Chunguang, Ren Xiaoyun, Dai Yueyou, Feng Shuying 2025, 29 (25):  5434-5442.  doi: 10.12307/2025.514 Abstract ( 54 )   PDF (1407KB) ( 195 )   Save BACKGROUND: Tumor microenvironment can participate in the occurrence and development of gastric cancer and promote chemotherapy resistance in various ways. Among them, the tumor microenvironment crosstalk mediated by exosomal miRNAs can induce matrix reprogramming, participate in tumor heterogeneity, and form a microenvironment conducive to tumor proliferation, migration, invasion, immune escape, and chemotherapy resistance.  OBJECTIVE: To review the mechanism of action of exosomal miRNAs in the microenvironment of gastric cancer and its application in the diagnosis and prognosis assessment of gastric cancer in recent years.  METHODS: “Exosomal miRNAs, gastric cancer, angiogenesis, apoptosis, proliferation, migration, autophagy, invasion, immune response, chemotherapy resistance, biomarker” for English search terms and “exosomal miRNAs, gastric cancer” for Chinese search terms were searched in PubMed and CNKI databases. The search period was from 2017 to 2024. After preliminary screening by reading the title and abstract, the articles with poor correlation and repeated content were excluded, and 77 articles were finally included for induction and discussion. RESULTS AND CONCLUSION: (1) Exosomes, as important carriers of intercellular information exchange, can carry a variety of information substances such as miRNA, and realize intercellular signal transmission through three ways: activation of cell surface receptors on target cells, fusion with the plasma membrane of recipient cells, and endocytosis. (2) Exosomal miRNAs play an important role in the progression of gastric cancer by regulating the proliferation, apoptosis, autophagy, angiogenesis, invasion and metastasis, immune response, and the formation of drug resistance of gastric cancer cells. (3) The interaction between miRNAs and target mRNA and its regulatory network are widely found in tumorigenesis and human cancer development. Different types of exosomal miRNAs have different effects on the regulation of apoptosis of gastric cancer cells, and the effects of different exosomal miRNAs on apoptosis related proteins and pathways of gastric cancer cells are screened. Rational use of its inducers or inhibitors can regulate the apoptosis level of gastric cancer cells. (4) Exosomal miRNAs of different cell origin play an important role in the establishment of tumor microenvironment, angiogenesis, immune response, and chemotherapy resistance by inducing M1-polarized macrophages to M2 type. (5) Exosomal miRNAs exist extensively and stably in blood and other body fluids, and their differential expression in patients with gastric cancer can be used as a basis for diagnosis, prognosis, and treatment of patients with gastric cancer. Currently, exosomal miRNAs widely studied as biomarkers include miR-379-5p, miR-590-5p, miR-29s, miR-21, etc. Among them, the sensitivity and specificity of miR-590-5p are 63.7% and 86%, respectively. The expression level of miR-590-5p is closely related to the overall survival rate and the depth of invasion of gastric cancer patients. (6) The design of exosomal miRNAs mimics or inhibitors and their targeted delivery to the tumor site using nano-delivery vectors (such as exosomes and liposomes) to restore the normal level of miRNAs may be a new strategy for the treatment of gastric cancer. (7) Although exosomal miRNAs have great application prospects in the diagnosis and treatment of gastric cancer patients, there are still some problems to be solved. For example, the potential targets and mechanisms of exosomal miRNAs have not been fully explored, and their effectiveness and safety need to be further confirmed. The extraction and purification of exosomes lack standardized large-scale preparation processes. Figures and Tables | References | Related Articles | Metrics

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Main pathways, roles, and regulatory mechanisms of intercellular mitochondrial transfer Li Xingfu, Zhou Guangqian, Lu Wei 2025, 29 (25):  5443-5453.  doi: 10.12307/2025.515 Abstract ( 268 )   PDF (1132KB) ( 407 )   Save BACKGROUND: Mitochondrial dysfunction leads to cellular senescence and apoptosis, exacerbating tissue damage. Intercellular mitochondrial transfer in injured cells restores mitochondrial function, offering potential therapeutic strategies for mitochondria-related diseases. OBJECTIVE: To review the effects and regulatory mechanisms of intercellular mitochondrial transfer. METHODS: A comprehensive literature search was conducted on mitochondrial transfer between cells in the CNKI and PubMed databases from 2014 to 2024. The Chinese and English search terms used were “mitochondrial transfer, tunneling nanotubes, gap junctions, microvesicles, cell fusion.” Eventually, a total of 74 articles were analyzed. RESULTS AND CONCLUSION: (1) The present review provides a comprehensive overview of the four principal mechanisms underlying mitochondrial transfer between cells, encompassing tunneling nanotubes, gap junctions, cell fusion, and microvesicles. (2) This article provides a comprehensive analysis of the pivotal roles played by intercellular mitochondrial transfer, encompassing material exchange, transmission of information, enhancement of host cell mitochondrial function, attenuation of oxidative stress, augmentation of cellular proliferation activity, anti-inflammatory effects, and anti-aging properties. (3) The article provides a comprehensive overview of the main regulatory mechanisms involved in cell mitochondria transfer. These include the promotion of tunneling nanotube formation and mitochondrial transfer by Miro 1, dependence of tunneling nanotubes-mediated mitochondrial transfer on host cell cyclic ADP ribose hydrolase expression, induction of tunneling nanotube formation in an oxidative stress environment, Ca2+-dependent gap junctions, influence of Cx43 on gap junction formation, contribution of Ras1 and actin activation to cell fusion, and involvement of actin and Rab6 in the regulation of mitochondrial exocytosis, activation of actin and NAD+-CD38-cADPR-Ca2+ signaling pathways for promoting mitochondrial entry. (4) The transfer of mitochondria occurs via tunneling nanotubes, gap junctions, microvesicles, and cell fusion under the influence of cell signaling proteins, proteins associated with cellular dynamics, and oxidative stress. (5) Mitochondrial transfer plays a pivotal role in facilitating both material and information exchange between cells, thereby intimately linking to the onset and progression of diseases, which can provide new ideas for the treatment of mitochondria-related diseases. However, further investigations are warranted to unravel the effects and regulatory mechanisms of intercellular mitochondrial transfer.  Figures and Tables | References | Related Articles | Metrics

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Exercise prevention and treatment of Parkinson’ s disease mediated by brain-derived neurotrophic factor: role and mechanism Lei Senlin, Chen Xiaoan, Chen Ping, Wang Zhaofeng 2025, 29 (25):  5454-5468.  doi: 10.12307/2025.503 Abstract ( 111 )   PDF (3781KB) ( 181 )   Save BACKGROUND: Exercise interventions, recognized for their economic and non-pharmaceutical efficacy, have demonstrated the potential to upregulate brain-derived neurotrophic factor levels, thereby offering a therapeutic approach to the prevention and management of Parkinson’s disease. However, the specific mechanisms by which exercise targeting brain-derived neurotrophic factor expression to delay Parkinson’s disease onset and progression are not clear.  OBJECTIVE: To explore the interplay between brain-derived neurotrophic factor and Parkinson’s disease, to analyze the specific regulatory effect and mechanism of exercise on the expression of brain-derived neurotrophic factor in the pathological state of Parkinson’s disease, to review the improvement effect of different exercise methods mediated by brain-derived neurotrophic factor on Parkinson’s disease, to clarify the potential mechanism of exercise therapy targeting brain-derived neurotrophic factor in the prevention and treatment of Parkinson’s disease, in order to provide a new theoretical basis for exercise prevention and treatment of Parkinson’s disease. METHODS: A systematic literature review was conducted using “Parkinson’s disease, brain-derived neurotrophic factor, neuroprotection, dopamine, neuronal apoptosis, neuroinflammation, and synaptic plasticity” as Chinese keywords, and “Parkinson’s disease, BDNF, neuroprotection, neuroinflammation, and synaptic plasticity” as English keywords. Databases including CNKI, WanFang Data, PubMed, and Web of Science were searched for relevant articles published up to February 2024. Totally 98 core articles were selected based on inclusion and exclusion criteria.  RESULTS AND CONCLUSION: (1) Within the pathophysiological framework of Parkinson’s disease, exercise has been shown to stimulate the release of the myokine Irisin and to specifically enhance brain-derived neurotrophic factor expression, counteracting kynurenine pathway metabolic dysregulation. (2) Aerobic activities, notably specialized forms such as Running on a Wheel with Electrical Stimulation (rotarod walking exercise) in animals and Nordic Walking in humans, along with multimodal exercise regimens, have been demonstrated to significantly enhance brain-derived neurotrophic factor expression. This upregulation is instrumental in ameliorating the motor symptoms associated with Parkinson’s disease. Furthermore, brain-derived neurotrophic factor is implicated in the beneficial modulation of non-motor symptoms, including cognitive and sleep disturbances, through the practice of mind-body interventions like Tai Chi. (3) Exercise-induced high expression of brain-derived neurotrophic factor exerts a neuroprotective effect through several mechanisms: By upregulating the expression of anti-inflammatory cytokines such as interleukin-10, nerve growth factor-beta, and transforming growth factor-beta, and concurrently downregulating the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta , thereby suppressing the activation of microglia via the inhibition of the nuclear factor-kappa B signaling pathway, leading to a reduction in neuroinflammatory responses; by augmenting the activity of tyrosine hydroxylase, which facilitates the synthesis and release of dopamine. This is complemented by the inhibition of matrix metalloproteinase-3 and glycogen synthase kinase-3 beta, preventing the hyperphosphorylation of alpha-synuclein at serine 129, thus counteracting abnormal neuronal apoptosis. By inducing long-term potentiation and promoting the robust expression of post-synaptic density protein 95 and synaptophysin, thereby enhancing synaptic plasticity and exerting a neuroprotective influence that may delay the onset and progression of Parkinson’s disease. (4) Considering the pivotal role of brain-derived neurotrophic factor in Parkinson’s disease progression and treatment, targeted exercise therapies could advance “Exercise + Medicine” precision medicine for Parkinson’s disease. However, current research is limited by a narrow focus on motor symptoms and a lack of diverse exercise protocols. There is a need for more comprehensive, longitudinal studies using varied exercise modalities to better understand and address non-motor symptoms in Parkinson’s disease patients to improve the lack of research in the field of Parkinson’s disease exercise prevention and treatment.  Figures and Tables | References | Related Articles | Metrics

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Major histocompatibility complex regulates immune responses in Parkinson’s disease Guan Mengya, Ren Binbin, Wang Jingying 2025, 29 (25):  5469-5477.  doi: 10.12307/2025.531 Abstract ( 31 )   PDF (1228KB) ( 71 )   Save BACKGROUND: The immune response is strongly associated with the pathological development of Parkinson’s disease. Studies have shown that the major histocompatibility complex plays a key role in immune response. OBJECTIVE: To summarize the mechanism of major histocompatibility complex regulation of immune response and the effect on the pathological marker α-synuclein of Parkinson’s disease.  METHODS: “Parkinson’s disease, the major histocompatibility complex, innate immunity, adaptive immunity, microglia, T cell, B cell, α-syn, inflammation, MHC-I, MHC-II” were used as search terms to search the literature in PubMed database. Finally, 92 articles were included for reading analysis. RESULTS AND CONCLUSION: (1) Congenital immune response is involved in the occurrence and development of Parkinson’s disease, and the change of microglia’s pro-inflammatory and anti-inflammatory phenotypes may aggravate the degenerative changes of Parkinson’s disease. (2) The phenotype and function of T cells are related to the progression of Parkinson’s disease. Regulatory T cells promote the activation of anti-inflammatory microglia and inhibit Th subgroup. B-cell-mediated humoral immunity can clear pathological α-synuclein, and its specific mechanism needs further study. (3) The major histocompatibility complex is closely related to the occurrence of innate and adaptive immunity, and thus affects the inflammation of Parkinson’s disease. (4) α-Synuclein can regulate the activation of microglia and the expression of major histocompatibility complex, which leads to inflammatory changes in Parkinson’s disease. (5) α-Synuclein is closely related to the immune response of Parkinson’s disease and has become an important target for the treatment of Parkinson’s disease.    Figures and Tables | References | Related Articles | Metrics

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Role of the sirtuins in pyroptosis Li Wenjie, Li Ying, Meng Maohua, Zeng Xiao, Sun Jinyi, Luo Yuncai, Wang Huan, Lu Jing, Dong Qiang 2025, 29 (25):  5478-5485.  doi: 10.12307/2025.522 Abstract ( 89 )   PDF (1717KB) ( 181 )   Save BACKGROUND: Unlike non-inflammatory cell apoptosis, pyroptosis is a form of inflammatory cell death, characterized by membrane integrity disruption and release of pro-inflammatory intracellular substances. Thus, it is associated with various diseases. The sirtuin family is a group of histone deacetylases dependent on nicotinamide adenine dinucleotide. In addition to deacetylation, it also possesses other enzymatic activities such as desuccinylation, demalonylation, adenosine diphosphate-ribosylation and playing crucial roles in the regulation of pyroptosis.  OBJECTIVE: To review the role of the sirtuins in pyroptosis. METHODS: The first author conducted a search on PubMed, Web of Science, CNKI, and WanFang Data from inception to March 2024, using the Chinese and English search terms “Sirtuins, Sirtuin1, Sirtuin2, Sirtuin3, Sirtuin4, Sirtuin5, Sirtuin6, Sirtuin7, pyroptosis”, resulting in the inclusion of 71 articles. RESULTS AND CONCLUSION: (1) The sirtuin family all participates in the regulation of pyroptosis. (2) Overexpression of sirtuin1 and sirtuin4 can inhibit pyroptosis through various pathways, thus alleviating the damage caused by pyroptosis to the organism. (3) In addition to affecting the classical pathway of pyroptosis, sirtuin3 can also inhibit pyroptosis by enhancing mitochondrial reactive oxygen species scavenging capacity and mitosis. (4) Sirtuin5 is involved in the regulation of intracellular metabolism and energy balance, including energy intake, storage, and consumption. (5) Sirtuin6 can influence pyroptosis through various pathways and also affect macrophage M1 polarization, generation of reactive oxygen species, and cleavage of pyroptosis-related factor sclerotin D to inhibit pyroptosis. (6) Overexpression of sirtuin7 can suppress pyroptosis. (7) Sirtuin2, unlike other family members, can restrain pyroptosis only after knockdown, but there are fewer reports, requiring more in-depth and comprehensive research.  Figures and Tables | References | Related Articles | Metrics

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Transcriptomic analysis and drug prediction of basement membrane-related genes in different traditional Chinese medicine patterns of rheumatoid arthritis Liu Yuan, Qu Yuan, Wan Yakun, Guo Jingyu, Jiang Ping 2025, 29 (25):  5486-5500.  doi: 10.12307/2025.505 Abstract ( 84 )   PDF (10901KB) ( 19 )   Save BACKGROUND: Basement membrane genes are closely related to the occurrence and development of rheumatoid arthritis, but the role of basement membrane-related genes in the pathogenesis of rheumatoid arthritis under different traditional Chinese medicine patterns is not yet clear. OBJECTIVE: To explore the differences in the pathogenesis of rheumatoid arthritis with five different traditional Chinese medicine syndromes based on the analysis of basement membrane-related genes and transcriptomics, and to predict potential therapeutic drugs.  METHODS: Rheumatoid arthritis-related traditional Chinese medicine syndrome microarray data and basement membrane-related genes were collected from the GEO database. The differentially expressed genes were screened using the R-limma package, and the expression trends were analyzed using the Mfuzz package. The protein-protein interaction network was constructed using the STRING database and key genes were selected using UPset. The differentially expressed genes were subjected to gene set enrichment analysis (GSEA) and enrichment analysis using the R-clusterProfiler package. Receiver operating characteristics curves were plotted to evaluate the diagnostic value of core basement membrane-related targets for each of the five syndromes. The immune infiltration of each syndrome was calculated using the CIBERSORT algorithm. Finally, potential traditional Chinese medicines and small molecule drugs targeting core basement membrane-related genes for the treatment of different traditional Chinese medicine syndromes of rheumatoid arthritis were predicted using SymMap and COREMINE databases.  RESULTS AND CONCLUSION: (1) 67, 47, 59, 57, and 55 basement membrane-related differentially expressed genes were screened for the five traditional Chinese medicine syndromes of rheumatoid arthritis (obstruction syndrome, cold-dampness obstruction syndrome, liver-kidney deficiency syndrome, qi-blood deficiency syndrome, and blood stasis obstructing collaterals syndrome), with 5, 7, 5, 3, and 5 key targets identified, respectively. (2) The most enriched biological processes in each syndrome were extracellular matrix adhesion, immune cell migration, collagen metabolism, and extracellular matrix receptor interaction, PI3K-Akt, focal adhesion, and Rap1 signaling pathways. (3) According to the predictions, Smilax glabra, Sargentodoxa cuneata, and Polygonatum sibiricum have the most potential as traditional Chinese medicines for the treatment of the five traditional Chinese medicine syndromes of rheumatoid arthritis by affecting basement membrane-related genes. (4) These results indicate that abnormal expression of basement membrane-related genes may affect the occurrence and development of rheumatoid arthritis through the regulation of cell adhesion, immune cell migration, and inflammatory reactions, among other pathways. These effects vary among different syndromes, with ITGA6 serving as a common diagnostic marker for the five traditional Chinese medicine syndromes of rheumatoid arthritis. Traditional Chinese medicines with heat-clearing and detoxifying properties may be potential effective drugs for the treatment of different syndromes of rheumatoid arthritis. Figures and Tables | References | Related Articles | Metrics