1.Exercise-induced Mitohormesis in Counteracting Age-related Sarcopenia
Zi-Yi ZHANG ; Mei MA ; Hai BO ; Tao LIU ; Yong ZHANG
Progress in Biochemistry and Biophysics 2025;52(6):1349-1361
Sarcopenia, an age-related degenerative skeletal muscle disorder characterized by progressive loss of muscle mass, diminished strength, and impaired physical function, poses substantial challenges to global healthy aging initiatives. The pathogenesis of this condition is fundamentally rooted in mitochondrial dysfunction, manifested through defective energy metabolism, disrupted redox equilibrium, imbalanced dynamics, and compromised organelle quality control. This comprehensive review elucidates the central role of exercise-induced mitochondrial hormesis as a critical adaptive mechanism counteracting sarcopenia. Mitohormesis represents an evolutionarily conserved stress response wherein sublethal mitochondrial perturbations, particularly transient low-dose reactive oxygen species (ROS) generated during muscle contraction, activate cytoprotective signaling cascades rather than inflicting macromolecular damage. The mechanistic foundation of this process involves ROS functioning as essential signaling molecules that activate the Keap1 nuclear factor erythroid 2 related factor 2 (Nrf2) antioxidant response element pathway. This activation drives transcriptional upregulation of phase II detoxifying enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GPx), thereby enhancing cellular redox buffering capacity. Crucially, Nrf2 engages in bidirectional molecular crosstalk with peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α), the principal regulator orchestrating mitochondrial biogenesis through coordinated induction of nuclear respiratory factors 1 and 2 (NRF1/2) along with mitochondrial transcription factor A (Tfam), collectively facilitating mitochondrial DNA replication and respiratory complex assembly. Concurrently, exercise-induced alterations in cellular energy status, specifically diminished ATP to AMP ratios, potently activate AMP activated protein kinase (AMPK). This energy-sensing kinase phosphorylates PGC-1α while concomitantly stimulating NAD dependent deacetylase sirtuin 1 (SIRT1) activity, which further potentiates PGC-1α function through post-translational deacetylation. The integrated AMPK/PGC-1α/SIRT1 axis coordinates mitochondrial biogenesis, optimizes network architecture through regulation of fusion proteins mitofusin 1 (Mfn1), mitofusin 2 (Mfn2) and optic atrophy protein 1 (OPA1), and enhances clearance of damaged organelles via selective activation of mitophagy receptors BCL2 interacting protein 3 (Bnip1) and FUN14 domain containing 1 (FNDC1). Exercise further stimulates the mitochondrial unfolded protein response (UPRmt), increasing molecular chaperones such as heat shock protein 60 (HSP60) and HSP10 to preserve proteostasis. Within the mitochondrial matrix, SIRT3 fine-tunes metabolic flux through deacetylation of electron transport chain components, improving phosphorylation efficiency while attenuating pathological ROS emission. Distinct exercise modalities differentially engage these pathways. Aerobic endurance training primarily activates AMPK/PGC-1α signaling and UPRmt to expand mitochondrial volume and oxidative capacity. Resistance training exploits mechanical tension to acutely stimulate mechanistic target of rapamycin complex 1 (mTORC1) mediated protein synthesis while modulating dynamin related protein 1 (Drp1) phosphorylation dynamics to support mitochondrial network reorganization. High intensity interval training generates potent metabolic oscillations that rapidly amplify AMPK/PGC-1α and Nrf2 activation, demonstrating particular efficacy in insulin-resistant phenotypes. Strategically designed concurrent training regimens synergistically integrate these adaptations. Mitochondrial-nuclear communication through tricarboxylic acid cycle metabolites and mitochondrially derived peptides such as mitochondrial open reading frame of 12s rRNA-c (MOTS-c) coordinates systemic metabolic reprogramming, with exercise-responsive myokines including fibroblast growth factor 21 (FGF-21) mediating inter-tissue signaling to reduce inflammation and enhance insulin sensitivity. This integrated framework provides the scientific foundation for precision exercise interventions targeting mitochondrial pathophysiology in sarcopenia, incorporating biomarker monitoring and exploring pharmacological potentiators including nicotinamide riboside and MOTS-c mimetics. Future investigations should delineate temporal dynamics of mitohormesis signaling and epigenetic regulation to optimize therapeutic approaches for age-related muscle decline.
2.The protective effect of icaritin on D-galactose-induced TM4 cell junctional function damage
Zhi-Li YAO ; Hai-Xia ZHAO ; Xiao-Yu MA ; Guo-Qing FU ; Jie WU ; Lai-Xin SONG ; Chang-Cheng ZHANG
Chinese Pharmacological Bulletin 2024;40(9):1634-1641
Aim To investigate the mechanism of icar-itin(ICT)on D-galactose(D-gal)-induced TM4 ser-toli cell junctional function damage in vitro.Methods TM4 cells were divided into the normal control group and D-gal treatment group with different concentra-tions.The expression changes of TM 4 cell junction function-related proteins(ZO-1,Occludin,β-catenin and Cx43)and ERα/FAK signaling pathway-related proteins(ERα,FAK and pY397-FAK)were detected by Western blot.The concentration of ICT was screened by MTT method.TM4 cells were divided into normal control group,D-gal treatment group,and D-gal treatment+different concentrations of ICT group.The expression levels of the above proteins were detected by Western blot.Molecular docking was used to study the interaction between ERα and ICT,meanwhile predict the affinity between them.Finally,TM4 cells were di-vided into normal control group,D-gal treatment group,ERα inhibitor group,D-gal+ICT group,and ERα inhibitor+ICT group.The expression levels of the above proteins were detected by Western blot.Re-sults Compared with the normal control group,the ex-pression of junctional function-related proteins(ZO-1,Occludin,β-catenin and Cx43)and ERα/FAK signa-ling pathway-related proteins(ERα,FAK and pY397-FAK)were significantly down-regulated.After treat-ment with ICT,the expression of above proteins were significantly up-regulated.The docking results of ERα and ICT molecules revealed the formation of two hydro-gen bonds between Asp351 amino acid residue of ERα and ICT,with bond distances measuring 3.4? and 2.4?.Additionally,the docking binding energy be-tween them was found to be lower than-7 kcal·mol-1.After TM4 cells were treated with ERα inhibi-tor,the expression of above proteins and ERα/FAK signaling pathway-related proteins were significantly down-regulated,while the expression levels of the a-bove proteins did not change significantly after being given ICT protected group.Conclusions D-gal can cause damage to the junctional function of TM4 cells,and ICT can improve this damage,which may be related to the up-regulation of ERα/FAK signaling pathway.
3.Analysis of the efficacy of high tibial osteotomy combined with medial meniscus centralization in knee osteoarthritis
Li-Ming ZHU ; Jie GUAN ; Yi-Min CHEN ; Hai-Tao MA ; Jia-Kuan YE
China Journal of Orthopaedics and Traumatology 2024;37(2):173-178
Objective To explore the efficacy of high tibial osteotomy(HTO)combined with medial meniscus centraliza-tion in knee osteoarthritis.Methods A total of 26 patients who underwent surgery from October 2018 to October 2020 were re-viewed.Among them,14 patients underwent high tibial osteotomy combined with arthroscopic meniscus centralization surgery were centralized group,including 8 males and 6 females,with an average age of(50.2±1.4)years old and follow-up time of(16.8±4.0)months.Twelve patients with high tibial osteotomy were in the control group,including 6 males and 6 females,with an average age of(50.9±1.8)years and follow-up time of(19.0±4.8)months.Operation time,the knee Lysholm score,knee 2000 IKDC score,MRI,femoral tibial angle(FTA),hip knee ankle angle(HKA),and intraoperative and postoperative compli-cations were recorded.Results All the incisions healed without any complication.The operation time in the centralized group was longer than that in the control group[(65.0±2.1)min vs(52.0±2.1)min,P<0.05].The medial meniscus extrusion reduction value in the centralized group was significantly reduced compared with the control group[(2.8±1.4)mm vs(1.1±2.2)mm,P<0.05].The FTA,HKA,knee Lyshlom score,and 2000 IKDC score between two groups were no significantly(P>0.05).Postop-erative knee Lyshlom score and knee 2000 IKDC score improved in both groups(P<0.05).Conclusion HTO combined with centralization of medial meniscus can improve the reduction of medial meniscus and improve knee function.The medium and long-term curative effect still needs long-term follow-up of more cases.
4.Echinococcus multilocularis metacestode vesicle-derived EVs containing emu-miR-10-5p promote mouse hepatic stellate cell activation
Yu-Qi WANG ; Zhuo-Ma DAWA ; Chuan-Chuan LIU ; Hai-Ning FAN
Chinese Journal of Zoonoses 2024;40(5):454-463,482
This study investigated the role of Echinococcus multilocularis vesicle-derived extracellular vesicles(EVs)con-taining emu-miR-10-5p in regulating HSC activation in vitro.Mice were injected intraperitoneally with protoscoleces to con-struct a secondary alveolar echinococcosis model,and E.multilocularis vesicles were cultured in mice and identified by PCR.The EV structure in cultured vesicle tissue was observed by transmission electron microscopy.EVs were isolated from vesicle culture supernatants through differential-ultracentrifugation,and identified by transmission electron microscopy,nanoparticle size analysis,and western blotting.The activity of HSCs treated with different EV concentrations was detected with CCK-8 assays.The expression levels of α-SMA,and collagen Ⅰ and Ⅲ were detected by RT-qPCR and western blotting after EV treatment of HSCs.Bioinformatics analysis identified the specific miRNA emu-miR-10-5p.The proliferation of HSCs was detected with EdU after overexpression of emu-miR-10-5p,and the expression levels of α-SMA,collagen Ⅰ,and collagen Ⅲ in cells were detected by RT-qPCR and western blotting.Detection of α-SMA,collagen Ⅰ,and collagen Ⅲ expression levels in HSCs was performed after EVs were extracted from the culture supernatant of vesicular tissues with emu-miR-10-5p knockdown.E.multilocularis vesicles were successfully cultured from focal material in mice,and the E.multilocularis origin was confirmed through PCR amplification of specific genes.TEM observation of culture vesicles in-dicated abundant surface vesicular structures.E.multilocularis vesicle-derived EVs were isolated by differential-ultracentrifu-gation,and confirmed by TEM to be spherical and membrane like-structures.Vesicle-derived EVs were internalized by HSCs,and promoted the proliferation and activation of HSCs.Comprehensive analysis of miRNA sequencing results revealed emu-miR-10-5p expression in E.multilocularis-infected mouse serum,metacestode tissue,E.multilocularis-derived EVs,germi-nal layer cells,and protoscoleces.Moreover emu-miR-10-5p was confirmed to be present in higher amounts in E.multilocu-laris-derived EVs,according to RT-qPCR.Further studies confirmed that overexpression of emu-miR-10-5p promoted HSC proliferation and increased α-SMA,collagen Ⅰ,and collagen Ⅲ mRNA and protein expression levels in HSCs.In contrast,EVs extracted from culture supernatants after emu-miR-10-5p knockdown in vesicles did not increase a-SMA,collagen Ⅰ,and colla-gen Ⅲ mRNA and protein expression levels.E.multilocularis vesicle-derived EVs and emu-miR-10-5p thus promote the acti-vation of HSCs.
5.LncRNA 606938 Inhibits Proliferation of Colorectal Cancer Cells
Hai-Li WU ; Bing DUAN ; Jin-E DU ; Jia-Jing MA ; Zhuo-Yu LI
Chinese Journal of Biochemistry and Molecular Biology 2024;40(7):964-975
In recent years,the application of long non-coding RNAs(lncRNAs)in the treatment of dis-eases has been widely concerned.LncRNAs have been proved to play a crucial role in tumor therapy.They usually act as oncogene or suppressor genes to regulate the occurrence and development of tumors.Previously,our group discovered a new lncRNA 606938 that can be used as a target in colorectal cancer through transcriptome analysis.However,its molecular mechanism in colorectal cancer is still unclear.In this study,RT-qPCR test shows that lncRNA 606938 is low expressed in colorectal cancer cell lines com-pared with normal colon epithelial cells.The clonogenicity was decreased by 97%and 54.5%in lncRNA 606938 overexpressed DLD-1 and SW620 cells,respectively.The results of flow cytometry assay showed that overexpression of lncRNA 606938 caused cell cycle arrest at G1 phase(They were prolonged by 50.5%and 63.9%,respectively)and promoted apoptosis of colorectal cancer cells,which was increased by 1.9%and 3.3%,respectively.Western blot results showed that overexpression of lncRNA 606938 down-regulated the expression of related oncogenes(β-catenin,c-Myc,cyclin D1,cyclin D2,cyclin D3,CDK 4,CDK 6)in colorectal cancer cells,and the expression of tumor suppressor genes(TRIM33,caspase 2,and actived caspase 3)was up-regulated.The above results were reversed after knockdown of lncRNA 606938.Mechanistically,it has been confirmed through RNA pulldown assay,RIP assay,and Rescue assay that lncRNA 606938 can target and promote TRIM33 expression,thereby promoting the degradation of β-catenin and blocking the expression of β-catenin and its downstream oncogenes such as c-Myc and cycline D1 to inhibit the progression of colorectal cancer.This study elucidates the molecular mechanism by which the lncRNA 606938 targets TRIM33/β-catenin signaling pathway,inhibits the pro-liferation and promotes the apoptosis of colorectal cancer cells.This study reveals the potential of lncRNA 606938 as a tumor suppressor gene,providing new target and strategies for the clinical treatment of color-ectal cancer.
6.Intervention of traditional Chinese medicine in spermatogenic epithelium injury by regulating the ferroptosis pathway:Advances in studies
Jin-Tao WEI ; Zi-Yang MA ; Jun CAO ; Pei-Hai ZHANG
National Journal of Andrology 2024;30(5):450-455
The incidence of male infertility has been increasing year by year,and one of the major causes is testicular spermato-genic epithelial injury,which affects the spermatogenic function of the testis.Ferroptosis is a novel mode of cell death and plays an im-portant role in testicular cell injury.Some traditional Chinese medicines can intervene in the progression of testicular injury by regula-ting the ferroptosis pathway in testicular spermatogenic epithelia.This paper focuses on the effect of traditional Chinese drugs in regula-ting the ferroptosis pathway in testicular cells,and summarizes the advances in the studies of traditional Chinese medicines in the treat-ment of testicular spermatogenic epithelial injury,aiming to provide a theoretical basis for the selection of relevant medicines and their clinical application.
7.Double J-tube indwelling after transurethral seminal vesiculoscopy reduces recurrence of ejaculatory duct obstruction
Kun PANG ; Bo CHEN ; Deng PAN ; Hao XU ; Yu-Yang MA ; Hai-Luo WANG ; Wei-Ling WANG
National Journal of Andrology 2024;30(8):681-686
Objective:To introduce a surgical method involving the indwelling of double-J tubes(DJT)in the seminal vesicles after transurethral seminal vesiculoscopy(TSV)in order to reduce the recurrence of refractory ejaculatory duct obstruction(EDO).Methods:This randomized controlled trial included 67 EDO patients undergoing TSV in our hospitals,27 with(the trial group)and 29 without postoperative indwelling of DJTs in the seminal vesicles(the control group).We collected the general information on the pa-tients and TSV-related parameters,including age,body mass index(BMI),preoperative use of antibiotics,history of urinary tract dis-ease,operation time,hospital stay and intra-and postoperative complications,and performed comparative analyses particularly on the surgical effect,complications,recurrence rate and time to recurrence in the two groups of patients.Results:The patients in the trial and control groups were followed up for(40.5±10.6)and(32.5±14.8)months,respectively.There were no statistically signifi-cant differences in the baseline data,intra-and postoperative complications,and postoperative hospital days between the two groups(P>0.05).Compared with the controls,the patients in the trial group showed a significantly shorter operation time([62.8±6.1]vs[49.5±7.7]min,P<0.05)and a lower recurrence rate than the controls(18.5%vs 44.8%,P<0.05),but with no statisti-cally significant difference in the median time to recurrence(21.0 mo vs 22.0 mo,P>0.05).Conclusion:The novel technique of indwelling double-J tubes in the seminal vesicles after TSV can significantly reduce the recurrence rate of refractory EDO.
8.Quality evaluation of Yanyangke Mixture
Xiao-Lian LIANG ; Xiong-Bin GUI ; Yong CHEN ; Zheng-Teng YANG ; Jia-Bao MA ; Feng-Xian ZHAO ; Hai-Mei SONG ; Jia-Ru FENG
Chinese Traditional Patent Medicine 2024;46(6):1781-1787
AIM To evaluate the quality of Yanyangke Mixture.METHODS The HPLC fingerprints were established,after which cluster analysis,principal component analysis and partial least squares discriminant analysis were performed.The contents of liquiritin,rosmarinic acid,sheganoside,irisgenin,honokiol,monoammonium glycyrrhizinate,irisflorentin,isoliquiritin and magnolol were determined,the analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX SB-C18 column(5 μm,250 mmx4.6 mm),with the mobile phase comprising of 0.1%phosphoric acid-acetonitrile flowing at 1 mL/min in a gradient elution manner,and multi-wavelength detection was adopted.RESULTS There were ten common peaks in the fingerprints for twelve batches of samples with the similarities of more than 0.9.Various batches of samples were clustered into three types,three principal components displayed the acumulative variance contribution rate of 87.448%,peaks 5、14(honokiol),3(liquiritin),11(monoammonium glycyrrhizinate)and 15(asarinin)were quality markers.Nine constituents showed good linear relationships within their own ranges(r>0.999 0),whose average recoveries were 98.5%-103.6%with the RSDs of 0.92%-1.7%.CONCLUSION This stable and reliable method can provide a basis for the quality control of Yanyangke Mixture.
9.Analysis of etiology and risk factors of cerebral infarction in Zang nationality patients of different ages in Xizang Autonomous Region
Biao LIU ; Jianfeng MA ; Yufei ZHANG ; Yuhua ZHAO ; Hai XIONG
Chinese Journal of Neurology 2024;57(11):1227-1238
Objective:To analyze the etiology and risk factors of Zang nationality cerebral infarction patients of different ages in Xizang Autonomous Region, so as to provide basis for more targeted diagnosis, treatment and prevention of cerebral infarction in this region.Methods:The clinical data of 500 Zang nationality cerebral infarction patients hospitalized in Xizang Autonomous Region People′s Hospital from January 2019 to December 2023 were retrospectively analyzed. According to age, they were divided into young and middle-aged group (18-59 years old) and elderly group (60-75 years old). Baseline data, laboratory data and imaging results of patients in each group were collected and retrospectively analyzed.Results:The proportion of males in the young and middle-aged group ( n=267) [188 (70.41%)] was higher than that in the elderly group ( n=233) [130 (55.79%), χ 2=11.485, P=0.001]. The proportion of smokers [131 (49.06%) vs 74 (31.76%), χ 2=15.401], drinkers [121 (45.32%) vs 84 (36.05%), χ 2=4.417], high altitude polycythemia (HAPC)[ 51 (19.10%) vs 23 (9.87%), χ 2=8.406], hyperuricemia (HUA)[ 61 (28.90%) vs 34 (19.32%), χ 2=4.766], increased hemoglobin [152 (56.93%) vs 97 (41.63%), χ 2=6.677], hypertriglyceridemia [47 (17.60%) vs 18 (7.73%), χ 2=10.734], hypercholesterolemia [12 (4.94%) vs 3 (1.29%), χ 2=4.397], hyperlipidemia [79 (29.59%) vs 43 (18.45%), χ 2=8.360] in the young and middle-aged group was higher than that in the elderly group (all P<0.05). The proportion of hypertension [108 (40.44%) vs 158 (67.81%), χ 2=37.413], atrial fibrillation [5 (1.87%) vs 20 (8.58%), χ 2=11.797], hyperhomocysteinemia (HHcy)[159 (59.55%) vs 168 (72.10%), χ 2=8.664], abnormal creatinine [18 (6.74%) vs 29 (12.45%), χ 2=4.755], atherosclerosis [113 (42.32%) vs 145 (62.23%), χ 2=19.748], heart disease [135 (50.56%) vs 150 (64.38%), χ 2=9.690] in the young and middle-aged group was lower than that in the elderly group (all P<0.05). Multivariate Logistic regression analysis showed that hypertension ( OR=2.865, 95% CI 1.742-4.710) and HHcy ( OR=1.968, 95% CI 1.177-3.290) were risk factors of cerebral infarction in the elderly group. Smoking ( OR=1.848, 95% CI 1.017-3.360), HAPC ( OR=1.993, 95% CI 1.991-4.011), HUA ( OR=1.863, 95% CI 1.015-3.419) and living at the extremely high altitude ( OR=2.405, 95% CI 1.207-4.791) were risk factors of cerebral infarction in the young and middle-aged group. According to the TOAST etiological classification, the causes of stroke of other determined etiology and stroke of other undetermined etiology were complex and diverse, which were more common in the young and middle-aged group, while cardiac embolism was more common in the elderly group. Conclusions:There are significant differences in the risk factors and etiology of cerebral infarction in different age groups in Xizang Autonomous Region. The occurrence of cerebral infarction in elderly patients is significantly related to hypertension and HHcy, while the occurrence of cerebral infarction in young and middle-aged patients is significantly related to smoking, HAPC, HUA, and living in extremely high altitude areas. In clinical practice, diagnosis and treatment of cerebral infarction patients in different age groups should have different focuses.
10.Effectiveness and safety of laparoscopic-assisted liposuction for treatment of gynaecomastia
Zhiqiang MA ; Jianxin HE ; Ruonan WANG ; Wei GUO ; Mengyuan CHEN ; Hai LU ; Bingshuai SHI
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(5):501-505
Objective:To explore the effectiveness and safety of laparoscopic-assisted liposuction in the treatment of gynecomastia.Methods:A retrospective study was conducted on 115 male breast development patients from January 2021 to May 2023 at the First Affiliated Hospital of Henan University and Shaoguan Hospital of Southern Medical University. The patients were divided into two groups based on surgical methods: the laparoscopic combined liposuction technique group (observation group) and the traditional areola incision group (control group). The control group consisted of 59 cases, aged between 18 and 52 years (26.2±5.2); There were 56 cases in the observation group, aged between 18 and 55 years (26.5±5.2). The differences in surgical time, intraoperative blood loss, drainage tube removal time, incidence of surgical complications, postoperative drainage volume, pain visual analog scale (VAS), and patient satisfaction were compared between two groups of patients.Results:The intraoperative bleeding volume, drainage tube removal time, and postoperative drainage volume in the observation group were 12.25±2.23, 2.85±0.53, and 80.52±7.53, respectively, all of which were lower than those in the control group (26.53±2.35, 4.22±0.59, 81.25±8.54, respectively), and the differences were statistically significant (all P<0.05).The incidence of sensory abnormalities in the nipple areola area of the observation group was 1.8% (1/56), which was lower than the 10.2% (6/59) of the control group, and the difference was statistically significant ( P<0.05).The postoperative breast shape, nipple shape, and incision score of the observation group were 81.15±18.52, 77.85±22.15, and 72.58±10.56 points, respectively, all higher than the control group's 69.34±18.48, 78.12±21.75, and 60.35±9.35 points, and the differences were statistically significant (all P<0.05). Conclusions:Laparoscopic combined with liposuction technology for the treatment of gynecomastia can reduce intraoperative bleeding and postoperative drainage volume and shorten the time for removing drainage tubes with better safety.

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