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.Interventional Effect and Mechanisms of Renqing Mangjue on MNNG-induced Malignant Transformation of Gastric Mucosal Epithelial Cells
Peiping CHEN ; Fengyu HUANG ; Xinzhuo ZHANG ; Xiangying KONG ; Ziqing XIAO ; Yanxi LI ; Xiaohui SU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):69-77
ObjectiveThis study aimed to investigate the intervention effect of Renqing Mangjue on the malignant transformation of gastric mucosal epithelial cells induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and to explore its molecular mechanism in preventing precancerous lesions of gastric cancer based on the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. MethodsHuman gastric mucosal epithelial cells (GES-1) were initially induced by MNNG to establish a precancerous cell model (MC cells). The effective concentration of MNNG for inducing malignant transformation in GES-1 cells was screened using the cell proliferation activity decection (CCK-8) assay, and the effective concentration of Renqing Mangjue for inhibiting the proliferation of transformed GES-1 cells was also determined. GES-1 cells were divided into a blank control group, a model group, and treatment groups with Renqing Mangjue at concentrations of 1, 3, 10, and 30 mg·L-1. Furthermore, the effects of Renqing Mangjue on the migratory ability and epithelial-mesenchymal transition (EMT) characteristics of GES-1 malignant transformed cells were evaluated using Transwell migration assays, wound healing assays, and real-time quantitative reverse transcription polymerase chain reaction (Real-time PCR). Additionally, candidate chemical components and target sites of Renqing Mangjue were obtained from the TCMIP v2.0 database, and disease targets at various stages of gastric cancer precursors were sourced from the Gene Expression Omnibus (GEO) database. Pathway enrichment analysis was performed using the Metascape database to predict the potential mechanisms of action of Renqing Mangjue. Finally, the protective mechanism of Renqing Mangjue against gastric cancer precursors was validated through Western blot analysis. ResultsAt a concentration of 20 μmol·L-1, MNNG exhibited an inhibition rate of approximately 50% on GES-1 cells (P<0.01), and at this concentration, the GES-1 cells displayed biological characteristics indicative of malignant transformation. In contrast, Renqing Mangjue had no significant effect on the proliferation of normal GES-1 cells, but significantly inhibited the proliferation of MC cells (P<0.01) and markedly reduced their migratory capacity (P<0.01). Moreover, it also increased the mRNA expression level of E-cadherin during the EMT process (P<0.05), while inhibiting the expression of both N-cadherin and the transcription factor Snail mRNA (P<0.05, P<0.01). Network predictions suggested that Renqing Mangjue may prevent gastric cancer precursors through modulating the cGMP/PKG and MAPK/ERK signaling pathways. Furthermore, Western blot results indicated that Renqing Mangjue upregulated the expression of PKG and NPRB (B-type natriuretic peptide receptor) proteins in the cGMP/PKG pathway (P<0.01), while downregulating the expression of the downstream proteins MEK and ERK (P<0.05, P<0.01). ConclusionIn summary, Renqing Mangjue can prevent gastric cancer precursors by inhibiting the proliferation and migration of malignant transformed GES-1 cells, thereby delaying the EMT process. The underlying mechanisms may be related to the activation of the cGMP/PKG pathway and the inhibition of the MEK/ERK signaling pathway.
3.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
4.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
5.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
6.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
7.Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues
Yuqing JIANG ; Mingcheng XUE ; Lu OU ; Huiquan WU ; Jianhui YANG ; Wangzihan ZHANG ; Zhuomin ZHOU ; Qiang GAO ; Bin LIN ; Weiwei KONG ; Songyue CHEN ; Daoheng SUN
Tissue Engineering and Regenerative Medicine 2025;22(2):211-224
BACKGROUND:
The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.
METHODS:
We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.
RESULTS:
Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results.
CONCLUSION
This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.
8.Efficacy analysis of blood inflammation and liver function indexes in ICP diagnosis and delivery mode prediction
Yuanyan ZHANG ; Lingling ZHANG ; Lin KONG ; Yanting CHEN ; Qiyun HUANG ; Lichun TANG
Chongqing Medicine 2024;53(4):522-527
Objective To observe the changes of laboratory blood indexes in patients with intrahepatic cholestasis of pregnancy(ICP),and analyze the value of blood inflammation indexes and liver function indexes in the diagnosis of ICP and the prediction of delivery mode.Methods A total of 251 patients diagnosed with ICP in this hospital from January 2021 to December 2022 were selected as the ICP group,and another 200 healthy pregnant women were selected as the control group.The patients with ICP were further divided into the severe ICP group(n=47)and the mild ICP group(n=204),the vaginal delivery group(n=113)and the cesarean section group(n=138)according to the severity of ICP and delivery mode.Mann-Whitney U test was used for comparison of parameters between groups,and Spearman method was used for correlation analy-sis.Receiver operating characteristic(ROC)curves were used to evaluate the efficacy of laboratory indicators in diagnosing ICP and predicting delivery mode.Results Neutrophil/lymphocyte ratio(NLR)[6.01(4.45,8.37)vs.3.36(4.12,3.51)]and aspartate transaminase(AST)level[20.00(16.00,33.00)U/L vs.15.00(13.00,18.00)U/L]in the ICP group were significantly higher than those in the control group(P<0.05),and NLR in the severe ICP group was significantly higher than that in the mild ICP group[4.93(3.87,7.35)vs.4.14(3.12,5.17),P<0.05].Correlation analysis showed that NLR was positively correlated with AST level(r=0.279,P<0.001)and ICP severity(r=0.139,P=0.028)in patients with ICP.The area under ROC curve(AUC)of NLR combined with AST for ICP diagnosis was 0.882(95%CI:0.851-0.913).In ad-dition,cholinesterase(CHE)[6 020.00(5 499.50,6 703.50)U/L vs.5 341.50(4 651.75,6 259.25)U/L]and prealbumin(PA)[199.00(177.71,225.20)mg/Lvs.169.17(139.18,204.40)mg/L]levels in the va-ginal delivery group were significantly higher than those in the cesarean section group(P<0.05),and the AUC of CHE combined with PA for predicting vaginal delivery in ICP patients was 0.727(95%CI:0.664-0.789).Conclusion NLR and AST have potential value in the diagnosis of ICP,and CHE and PA have poten-tial value in predicting delivery mode of ICP patients.
9.Ilex pubescens var.kwangsiensis improved radiation-induced cognitive impairment of mice by inhibiting oxidative stress
Ting LI ; Gaigai HE ; Linsha KONG ; Lin RUAN ; Shaojun WANG ; Li WEI
Chinese Journal of Neuroanatomy 2024;40(1):57-64
Objective:To investigate the improvement of radiation-induced cognitive dysfunction and its preliminary mechanism by Ilex pubescens var.kwangsiensis.Methods:SPF grade male Kunming mice were randomly divided into control group(Control),Ilex pubescens var.kwangsiensis(IP),radiation group(Rad)and radiation+Ilex pubescens var.kwangsiensiss group(Rad+IP),with 10 mice in each group.Morris water maze test and dark avoidance test were used to detect the changes in cognitive function of mice before and after drug intervention.Hematoxylin-eosin(HE)staining and electron microscopy were used to observe the changes of brain histopathology and ultrastructure in the hip-pocampus of mice.The expressions of nuclear factor E2-associated factor 2(Nrf2),heme oxygenase 1(HO-1),man-ganese superoxide dismutase(MnSOD),B-cell lymphoma/leukemia-2(Bcl-2)and Bcl-2 associated X protein(Bax)were detected by immunohistochemical assay.Results:The expressions of MnSOD and Bcl-2 in hippocampal tissue of mice in Rad group were significantly decreased,the expressions of Nrf2,Bax and HO-1 were significantly increased,and the nuclear translocation of Nrf2 was also significantly increased.After intervention,he expressions of MnSOD,Nrf2 and HO-1 were significantly increased,and the apoptosis rate was significantly decreased.Conclusion:Ilex pu-bescens var.kwangsiensis improved cognitive dysfunction in mice after radiation,and the mechanism may be related to Nrf2 activation and regulation of HO-1 transcription and expression,reducing oxidative stress damage.
10.Endo-beta-N-acetylglucosaminidase: Possible Functions and Mechanisms
Xin-Rong LU ; Yong-Liang TONG ; Wei-Li KONG ; Lin ZOU ; Dan-Feng SHEN ; Shao-Xian LÜ ; Rui-Jie LIU ; Shao-Xing ZHANG ; Yu-Xin ZHANG ; Lin-Lin HOU ; Gui-Qin SUN ; Li CHEN
Progress in Biochemistry and Biophysics 2024;51(5):985-999
Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

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