1.Epigenetic changes and exercise regulation:mechanisms underlying skeletal muscle aging and improvement
Rao FAN ; Jianda KONG ; Lin LI ; Teng ZHAI ; Zirou YANG ; Lei ZHU
Chinese Journal of Tissue Engineering Research 2025;29(2):419-429
BACKGROUND:Muscle aging is closely related to various epigenetic changes,and exercise has a certain regulatory effect on these epigenetic changes.However,the specific mechanism is not fully understood. OBJECTIVE:To review the epigenetic mechanisms of skeletal muscle and how exercise can improve skeletal muscle aging and promote adaptive changes in muscle through these epigenetic mechanisms,aiming to provide a more comprehensive understanding of skeletal muscle aging and disease mechanisms. METHODS:During the period from June 1st to August 1st,2023,literature searches were conducted for relevant literature published from database inception to August 2023 in databases including Web of Science,PubMed,CNKI,WanFang,and VIP.The search terms used included"skeletal muscle,""muscle,""aging,""older adult,""aging,""exercise,""physical exercise,""epigenetic,"and"epigenetics"in Chinese as well as"skeletal muscle,muscle,aging,older adult,senescence,age,exercise,sports,physical activity,epigenetic,epigenetics"in English.Boolean logic operators were used to connect the search terms for retrieval,and corresponding strategies were developed.According to the predetermined inclusion and exclusion criteria,70 eligible articles were selected. RESULTS AND CONCLUSION:Epigenetics refers to the phenomenon where gene expression and function are regulated without changes in gene sequence,and epigenetic changes in skeletal muscle are an important field.The epigenetic mechanisms of skeletal muscle play an important role in muscle aging,mainly involving DNA methylation,histone modification,regulation of non-coding RNAs,chromatin remodeling,changes in mitochondrial function and expression changes of aging-related genes.Exercise significantly regulates the epigenetics of skeletal muscle,including promoting DNA methylation,muscle histone modification,regulating miRNA expression,and regulating lncRNA expression,regulating muscle factors(such as interleukin-6),regulating mitochondrial function(such as peroxisome proliferators-activated receptors γ co-activator 1α).Future studies are recommended for long-term,cross-diverse population-based exercise interventions;the application of multi-omics techniques such as proteomics and metabolomics;strengthening the understanding of epigenetic changes at the single-cell level;cross-species comparative studies as well as human clinical trials for the translation of animal model findings to humans;strategies for combining exercise and pharmacological interventions to assess their synergistic effects;and epigenetic studies of crosstalk interactions between skeletal muscle and different organs.
2.Effect of demethylase FTO knockout on 5-HT-induced abnormalities of coronary smooth muscle contractile function in mice with diabetes mellitus
Zi-fan WANG ; Liu-xiang JIANG ; Mei-ying LIANG ; Meng-yun LIU ; Mei-jiang CHEN ; Hui YANG ; Fang RAO ; Chun-yu DENG
Chinese Pharmacological Bulletin 2025;41(2):315-322
Aim To explore the influence of demethy-lase fat mass and obesity-related genes(FTO)on the abnormal contractile function of diabetic coronary smooth muscle.Methods Smooth muscle specific FTO knockout mice(FTOSMKO)were prepared by Cre-loxP recombinant technology.They were divided into four groups:control(WT)group,diabetes model group(DM),FTO knockout group(FTOSMKO),and FTOSMKO diabetic group(FTOSMKO-DM),with 15 mice in each group.Diabetic mice were prepared by intraperitoneal injection of streptozotocin(STZ);the remaining mice were injected with an equal amount of citric acid-sodi-um citrate buffer.The effects of 5-HTon the contractile response of coronary artery smooth muscle in the four groups of mice were observed by the technique of small-vessel ring tensiometry.Western blot and Dot blot were used to detect the changes of FTO protein and N6-methyladenine(m6A)methylation modification levels in mouse vascular tissues.Results Compared with the WT group,the DM group had significantly higher blood glucose(P<0.01)and lower body weight(P<0.05);the level of FTO protein in aorta of DM group increased(P<0.01),and the level of m6A methylation modification decreased(P<0.01).The 5-HT-induced contractile response significantly de-creased in the DM group compared with the WT group(P<0.01),whereas the contractile response signifi-cantly increased in the FTOSMKO-DM group compared with the DM group(P<0.01);the non-L-type calci-um channel-mediated vascular smooth muscle contrac-tile response was enhanced in the FTOSMKO-DM group,among which,the contractions induced by 1,4,5-triphosphate inositol receptor(IP3R)and caffeine-ac-tivated ranine receptor(RyR)mediated by sarcoplas-mic reticulum calcium release both significantly in-creased(P<0.05).Conclusions Specific knock-down of smooth muscle FTO improves coronary artery responsiveness to the vasoconstrictor 5-HT in diabetic mice,which may be related to abnormalities in the FTO-mediated 5-HT receptor signaling pathway.
3.Clinical application and long-term outcomes of transoral robotic surgery for resection of parapharyngeal space tumors
Lingzhao MENG ; Fan YANG ; Yuansheng RAO ; RAI BIKASH ; Jugao FANG
Journal of Clinical Medicine in Practice 2025;29(7):38-42
Objective To evaluate the safety,efficacy,and long-term outcomes of transoral ro-botic surgery(TORS)for the resection of parapharyngeal space tumors(PPST).Methods A retro-spective analysis was conducted on clinical data from 16 patients who underwent TORS for PPST re-section.Surgical outcomes,postoperative pathological findings,and complication rates were ob-served.Follow-up evaluations were performed to assess patient satisfaction,swallowing function re-covery,and tumor recurrence.Results Except for one patient who required an additional neck inci-sion,the remaining 15 patients successfully completed the surgery via the oral route.None of the pa-tients underwent tracheotomy or mandibulotomy.The mean surgical duration was 43.9 minutes,with an average tumor diameter of 4.5 cm resected.The mean intraoperative blood loss was 35.3 mL.Patients resumed oral intake after an average of 3.8 days and had a mean postoperative hospital stay of 8.3 days.Postoperative pathological examination revealed that the most common tumor type was pleomorphic adenoma(56.2%,9/16),followed by schwannoma(25.0%,4/16),with one case of basal cell adenoma,cyst,and lipoma,respectively.One patient experienced transient Horner's syndrome,two had wound dehiscence that healed spontaneously,and one had spontaneous wound healing after drainage tube dislodgement.With a mean follow-up of 79.5 months,no tumor recurrence or severe complications were observed.All patients had good swallowing function and were satisfied with the surgical outcomes.Conclusion TORS for PPST resection offers advantages such as clear surgical visualization,direct surgical access,minimal blood loss,reduced trauma,favorable cosmetic re-sults,and rapid postoperative recovery.It also demonstrates good long-term outcomes,with high safety and efficacy.
4.Application value of low-temperature plasma bipolar forceps in thyroid cancer surgery
Lingzhao MENG ; Xiaopeng QU ; Pengyu TAO ; Fan YANG ; Yuansheng RAO ; Ru WANG ; Jugao FANG
Journal of Capital Medical University 2025;46(3):553-558
Objective To explore the application value of low-temperature plasma bipolar forceps in open thyroid cancer surgery.Methods The clinical data of 30 patients with differentiated thyroid cancer treated with low-temperature plasma bipolar forceps by our team from May 2021 to October 2024 were retrospectively analyzed.And 30 patients with differentiated thyroid cancer treated with monopolar electrocautery+ultrasonic scalpel were selected as the control group.The surgical procedures for both groups were thyroid lobectomy,isthmus resection+ipsilateral level Ⅵ lymph node dissection.The age,gender,body mass index(BMI),tumor TNM stage,operation time,intraoperative blood loss,48 h postoperative drainage volume,and surgical complications of the two groups were compared.Results There were no significant differences in age,gender,BMI,and tumor TNM stage between the two groups.The operation time,intraoperative blood loss,48 h postoperative drainage volume,and the incidence of postoperative transient hypoparathyroidism in the low-temperature plasma bipolar forceps group were significantly less than those in the control group(P<0.05).There were no occurrences of postoperative subcutaneous hematoma,permanent recurrent laryngeal nerve palsy,and permanent hypoparathyroidism in both groups.Conclusion In thyroid cancer surgery,low-temperature plasma bipolar forceps can not only achieve fine detailed operations,but also effectively protect the blood supply of the recurrent laryngeal nerve,superior laryngeal nerve,and parathyroid glands.It has less trauma and a faster postoperative recovery,and is worthy of clinical promotion and application.
5.Study on mechanism of Vaccarin improving EMT in renal fibrosis model mice through regulating STAT3
Meng-jiao CUI ; Qi-ming XU ; Yu CAO ; Ye-nan FAN ; Yi-qing YANG ; Guang-bo GE ; Wen-rui LIU ; Jian-rao LU ; Jing HU
Chinese Pharmacological Bulletin 2025;41(4):745-752
Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.
6.Study on mechanism of Vaccarin improving EMT in renal fibrosis model mice through regulating STAT3
Meng-jiao CUI ; Qi-ming XU ; Yu CAO ; Ye-nan FAN ; Yi-qing YANG ; Guang-bo GE ; Wen-rui LIU ; Jian-rao LU ; Jing HU
Chinese Pharmacological Bulletin 2025;41(4):745-752
Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.
7.Application value of low-temperature plasma bipolar forceps in thyroid cancer surgery
Lingzhao MENG ; Xiaopeng QU ; Pengyu TAO ; Fan YANG ; Yuansheng RAO ; Ru WANG ; Jugao FANG
Journal of Capital Medical University 2025;46(3):553-558
Objective To explore the application value of low-temperature plasma bipolar forceps in open thyroid cancer surgery.Methods The clinical data of 30 patients with differentiated thyroid cancer treated with low-temperature plasma bipolar forceps by our team from May 2021 to October 2024 were retrospectively analyzed.And 30 patients with differentiated thyroid cancer treated with monopolar electrocautery+ultrasonic scalpel were selected as the control group.The surgical procedures for both groups were thyroid lobectomy,isthmus resection+ipsilateral level Ⅵ lymph node dissection.The age,gender,body mass index(BMI),tumor TNM stage,operation time,intraoperative blood loss,48 h postoperative drainage volume,and surgical complications of the two groups were compared.Results There were no significant differences in age,gender,BMI,and tumor TNM stage between the two groups.The operation time,intraoperative blood loss,48 h postoperative drainage volume,and the incidence of postoperative transient hypoparathyroidism in the low-temperature plasma bipolar forceps group were significantly less than those in the control group(P<0.05).There were no occurrences of postoperative subcutaneous hematoma,permanent recurrent laryngeal nerve palsy,and permanent hypoparathyroidism in both groups.Conclusion In thyroid cancer surgery,low-temperature plasma bipolar forceps can not only achieve fine detailed operations,but also effectively protect the blood supply of the recurrent laryngeal nerve,superior laryngeal nerve,and parathyroid glands.It has less trauma and a faster postoperative recovery,and is worthy of clinical promotion and application.
8.Effect of demethylase FTO knockout on 5-HT-induced abnormalities of coronary smooth muscle contractile function in mice with diabetes mellitus
Zi-fan WANG ; Liu-xiang JIANG ; Mei-ying LIANG ; Meng-yun LIU ; Mei-jiang CHEN ; Hui YANG ; Fang RAO ; Chun-yu DENG
Chinese Pharmacological Bulletin 2025;41(2):315-322
Aim To explore the influence of demethy-lase fat mass and obesity-related genes(FTO)on the abnormal contractile function of diabetic coronary smooth muscle.Methods Smooth muscle specific FTO knockout mice(FTOSMKO)were prepared by Cre-loxP recombinant technology.They were divided into four groups:control(WT)group,diabetes model group(DM),FTO knockout group(FTOSMKO),and FTOSMKO diabetic group(FTOSMKO-DM),with 15 mice in each group.Diabetic mice were prepared by intraperitoneal injection of streptozotocin(STZ);the remaining mice were injected with an equal amount of citric acid-sodi-um citrate buffer.The effects of 5-HTon the contractile response of coronary artery smooth muscle in the four groups of mice were observed by the technique of small-vessel ring tensiometry.Western blot and Dot blot were used to detect the changes of FTO protein and N6-methyladenine(m6A)methylation modification levels in mouse vascular tissues.Results Compared with the WT group,the DM group had significantly higher blood glucose(P<0.01)and lower body weight(P<0.05);the level of FTO protein in aorta of DM group increased(P<0.01),and the level of m6A methylation modification decreased(P<0.01).The 5-HT-induced contractile response significantly de-creased in the DM group compared with the WT group(P<0.01),whereas the contractile response signifi-cantly increased in the FTOSMKO-DM group compared with the DM group(P<0.01);the non-L-type calci-um channel-mediated vascular smooth muscle contrac-tile response was enhanced in the FTOSMKO-DM group,among which,the contractions induced by 1,4,5-triphosphate inositol receptor(IP3R)and caffeine-ac-tivated ranine receptor(RyR)mediated by sarcoplas-mic reticulum calcium release both significantly in-creased(P<0.05).Conclusions Specific knock-down of smooth muscle FTO improves coronary artery responsiveness to the vasoconstrictor 5-HT in diabetic mice,which may be related to abnormalities in the FTO-mediated 5-HT receptor signaling pathway.
9.Relationship between serum miR-410-3p expression and knee soft tissue lesions in patients with rheumatoid arthritis
Hui RAO ; Sheng-Zhi JIANG ; Yu-Bei FAN ; Yu-Qing ZHOU ; Li-Hua ZHANG
Journal of Regional Anatomy and Operative Surgery 2024;33(2):137-140
Objective To explore the expression of serum miR-410-3p in patients with rheumatoid arthritis(RA)and its relationship with knee soft tissue lesions.Methods A total of 89 RA patients admitted to our hospital were selected and divided into the active group(42 cases)and the remission group(47 cases)according to disease activity score in 28 joints(DAS28).In addition,52 healthy volunteers underwent physical examination during the same period in our hospital were selected as the healthy group.The expression level of serum miR-410-3p was detected by RT-PCR,the lesions of knee soft tissue was examined by ultrasound,and the relationship between the expression of serum miR-410-3p and knee soft tissue lesions was analyzed by Pearson.Results The expression levels of serum miR-410-3p of patients in the active group and the remission group were lower than that in the healthy group(P<0.05),and the expression level of serum miR-410-3p of patients in the active group was lower than that in the remission group(P<0.05).The cartilage thicknesses of medial and lateral ankle of patients in the active group and the remission group were smaller than those in the healthy group(P<0.05),and the above indexes in the active group were smaller than those in the remission group(P<0.05).The depths of suprapatellar bursa fluid and synovial thicknesses of patients in the active group and the remission group were greater than those in the healthy group(P<0.05),and the depth of suprapatellar bursa fluid and synovial thickness of patients in the active group were greater than those in the remission group(P<0.05).The level of serum miR-410-3p in RA patients was positively correlated with the depth of suprapatellar bursa fluid and synovial thickness(P<0.05),and negatively correlated with the cartilage thicknesses of medial and lateral ankle(P<0.05).Conclusion Serum miR-410-3p expression level in RA patients is decreased,which was closely related to knee soft tissue lesions,detecting the changes of serum miR-410-3p level may provide a reference for the evaluation of knee soft tissue lesions.
10.Pharmacokinetic study of the complication of Ephedra sinica and Prunus armeniaca in bronchial asthma model rats
Linlin CHEN ; Jingen XIE ; Xuecheng FAN ; Qian RAO ; Tianyi YANG ; Jiayu TIAN ; Xiong XIAO ; Wenjun GAO ; Wenhong LI
China Pharmacy 2024;35(13):1588-1593
OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group, model group, E. sinica group (12 g/kg, calculated by raw drug, similarly hereinafter), P. armeniaca group (6 g/kg) and E. sinica-P. armeniaca drug-pair group (12 g/kg of E. sinica+6 g/kg of P. armeniaca), with 6 rats in each group. Except for the blank group, the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate, once a day, for 7 d. One hour before modeling every time, rats in each group were gavaged with the corresponding drug/normal saline, once a day, for 7 d. After the final administration and provocation of asthma, blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated (with geranylgeranyl as the internal standard), and the mass concentrations of ephedrine/pseudoephedrine, methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group, cmax and AUC0-21.33 h (or AUC0-10.67 h) of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group, while CLZ/F and VZ/F were significantly increased (P<0.05 or P<0.01); tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened (P< 0.05).Compared with P. armeniaca group, the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened, and CLZ/F was significantly increased (P<0.01); the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened, and the AUC0-10.67 h, CLZ/F, and VZ/F were significantly increased (P<0.01). CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids, thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

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