1.Regulation of Immune Function by Exercise-induced Metabolic Remodeling
Hui-Guo WANG ; Gao-Yuan YANG ; Xian-Yan XIE ; Yu WANG ; Zi-Yan LI ; Lin ZHU
Progress in Biochemistry and Biophysics 2025;52(6):1574-1586
Exercise-induced metabolic remodeling is a fundamental adaptive process whereby the body reorganizes systemic and cellular metabolism to meet the dynamic energy demands posed by physical activity. Emerging evidence reveals that such remodeling not only enhances energy homeostasis but also profoundly influences immune function through complex molecular interactions involving glucose, lipid, and protein metabolism. This review presents an in-depth synthesis of recent advances, elucidating how exercise modulates immune regulation via metabolic reprogramming, highlighting key molecular mechanisms, immune-metabolic signaling axes, and the authors’ academic perspective on the integrated “exercise-metabolism-immunity” network. In the domain of glucose metabolism, regular exercise improves insulin sensitivity and reduces hyperglycemia, thereby attenuating glucose toxicity-induced immune dysfunction. It suppresses the formation of advanced glycation end-products (AGEs) and interrupts the AGEs-RAGE-inflammation positive feedback loop in innate and adaptive immune cells. Importantly, exercise-induced lactate, traditionally viewed as a metabolic byproduct, is now recognized as an active immunomodulatory molecule. At high concentrations, lactate can suppress immune function through pH-mediated effects and GPR81 receptor activation. At physiological levels, it supports regulatory T cell survival, promotes macrophage M2 polarization, and modulates gene expression via histone lactylation. Additionally, key metabolic regulators such as AMPK and mTOR coordinate immune cell energy balance and phenotype; exercise activates the AMPK-mTOR axis to favor anti-inflammatory immune cell profiles. Simultaneously, hypoxia-inducible factor-1α (HIF-1α) is transiently activated during exercise, driving glycolytic reprogramming in T cells and macrophages, and shaping the immune landscape. In lipid metabolism, exercise alleviates adipose tissue inflammation by reducing fat mass and reshaping the immune microenvironment. It promotes the polarization of adipose tissue macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Moreover, exercise alters the secretion profile of adipokines—raising adiponectin levels while reducing leptin and resistin—thereby influencing systemic immune balance. At the circulatory level, exercise improves lipid profiles by lowering pro-inflammatory free fatty acids (particularly saturated fatty acids) and triglycerides, while enhancing high-density lipoprotein (HDL) function, which has immunoregulatory properties such as endotoxin neutralization and macrophage cholesterol efflux. Regarding protein metabolism, exercise triggers the expression of heat shock proteins (HSPs) that act as intracellular chaperones and extracellular immune signals. Exercise also promotes the secretion of myokines (e.g., IL-6, IL-15, irisin, FGF21) from skeletal muscle, which modulate immune responses, facilitate T cell and macrophage function, and support immunological memory. Furthermore, exercise reshapes amino acid metabolism, particularly of glutamine, arginine, and branched-chain amino acids (BCAAs), thereby influencing immune cell proliferation, biosynthesis, and signaling. Leucine-mTORC1 signaling plays a key role in T cell fate, while arginine metabolism governs macrophage polarization and T cell activation. In summary, this review underscores the complex, bidirectional relationship between exercise and immune function, orchestrated through metabolic remodeling. Future research should focus on causative links among specific metabolites, signaling pathways, and immune phenotypes, as well as explore the epigenetic consequences of exercise-induced metabolic shifts. This integrated perspective advances understanding of exercise as a non-pharmacological intervention for immune regulation and offers theoretical foundations for individualized exercise prescriptions in health and disease contexts.
2.Treadmill Exercise Improves Cognitive Dysfunction in Diabetic Mice by Regulating PANoptosis Through the p38 MAPK Signaling Pathway
Ke-Yan SHENG ; Yu-Yan CHEN ; Yuan GAO ; Bao-Wen ZHANG ; Meng ZHANG ; Zhi WANG ; Xian-Juan KOU
Chinese Journal of Biochemistry and Molecular Biology 2024;40(7):987-998
Cognitive dysfunction is one of the serious complications of type 2 diabetes.Exercise interven-tion has a certain effect on improving diabetes cognition,but the exact process remains ambiguous.This research aims to explore the impact and molecular processes of treadmill exercises in enhancing cognitive impairments in type 2 diabetic mice.Ten m/m 8-week-old male mice were used as the control group.Forty db/db mice,each 8 weeks old and male,were categorized into four distinct groups with each group containing 10 mice,including the db/db group(model group),db+Exe group(exercise group),db+Exe+SB203580 group(exercise combined with the p38 MAPK inhibitor group),db+SB203580 group(p38 MAPK inhibitor group).db+Exe group and db+Exe+SB203580 group were subjected to treadmill running intervention(40 min/time,5 times/week,a total of 8 weeks).db+Exe+SB203580 and db+SB203580 group were intraperitoneally injected with SB203580(5 mg/kg,5 times/week,8 weeks)2 hours before treadmill exercise.The results of body weights and fasting blood glucose measurement showed that 8-week treadmill exercise could significantly reduce the body mass and fasting blood glucose levels(P<0.01);the results of water maze showed that treadmill exercise improved cognitive dysfunction in diabetic mice(P<0.05).Immunofluorescence staining revealed that treadmill exercise diminished the fluorescence intensity of NLRP3 in hippocampus,and there was a significant difference in CA1 and CA3 regions(P<0.05).Treadmill exercise reduced the fluorescence intensity of PI in the hippocampus,and there was a significant difference in the DG region(P<0.01).The results of qRT-PCR revealed that treadmill exercise decreased IL-1β and IL-18 mRNA levels in hippocampus,with a notable difference in IL-1β mRNA levels(P<0.05).Western blotting analysis revealed that treadmill exercise reduced the concentrations of Caspase3,Caspase9 and Bax in hippocampus(P<0.01),reduced the concentrations of TXNIP,NLRP3,GSDMD-N,IL-1β,IL-18,Cleaved Caspase1 and Caspasel(P<0.05),decreased the levels of p-RIPK1,RIPK1,p-RIPK3 and RIPK3(P<0.05).After adding p38 inhibitors,treadmill ex-ercise combined with p38 inhibitor intervention further inhibited the expression of Caspase3,TXNIP,GS-DMD-N and IL-18(P<0.05),and the expression levels of Caspase9,Bax,NLRP3,IL-1β,Cleaved Caspase 1 and Caspase 1 also showed a downward trend.The expression of RIPK1 and p-RIPK3 in-creased significantly(P<0.05),and the protein expression levels of p-p38,p-RIPK1 and RIPK3 showed an upward trend.In conclusion,treadmill running intervention can effectively improve the cogni-tive dysfunction in type 2 diabetic mice,and its mechanism is partly through the p38 MAPK signaling pathway to regulate PANoptosis.
3.Prognostic Factors Affecting Recurrence in Peripheral T-Cell Lymphoma Patients with Different HDAC Levels
Ying-Xin LI ; Yi-Dan LI ; Pei WANG ; Hui-Jie JIAO ; Ying LI ; Jing ZHANG ; Xian-Hua YUAN
Journal of Experimental Hematology 2024;32(3):733-741
Objective:To analyze the distribution characteristics of prognostic factors affecting recurrence in peripheral T-cell lymphoma(PTCL)patients with different levels of histone deacetylase(HDAC)based on latent class analysis.Methods:112 PTCL patients who were treated in our hospital from September 2012 to September 2019 were selected and divided into recurrence group and non-recurrence group.The clinical data of the two groups of patients were compared.Multivariate logistic regression was used to analyze the risk factors for recurrence.Latent class analysis was used to compare the distribution characteristics of prognostic factors affecting recurrence between the high-risk group and the low-risk group.Results:There were 87 patients(77.68%)in recurrence group and 25 patients(22.32%)in non-recurrence group.The result of multivariate logistic regression showed that ECOG score ≥2,Ann Arbor stage Ⅲ-Ⅳ,IPI score>2,bone marrow involvement,elevated serum β2-microglobulin(β2-MG),short-term efficacy not reaching complete remission(CR)or partial remission(PR),and the high expression of HDAC were all independent risk factors for recurrence in patients with PTCL(P<0.05).The recurrence rate of patients with high HDAC levels was significantly higher than that of patiens with low HDAC levels(P<0.05).The results of cluster analysis showed that the risk of recurrence was obviously clustered,and the patients could be divided into high recurrence risk group(HDAC>5 points)and low recurrence risk group(HDAC≤5 points).The results of latent class analysis showed that patients with multiple risk factors account for a higher proportion in the high recurrence risk group,compared with the low recurrence risk group(P<0.05).Conclusion:There are differences in recurrence rates among PTCL patients with different HDAC levels and in distribution characteristics of risk factors between high recurrence risk and low recurrence risk groups.
4.Design of patient lifting aid
Xian-Ju YUAN ; Zi-Hong WANG ; Fei-Ba CHANG ; Hu LUO
Chinese Medical Equipment Journal 2024;45(4):111-115
Objective To design a lifting aid to enhance the loading and unloading efficiency of casualties in emergency rescue.Methods The lifting aid was composed of a lifting mechanism,a motorized control unit and a manual control unit,which used a pulley set to enhance working efficiency,achieved lateral patient translation via a separable and movable sleeping pad and realized electric and manual control by a motor and lever respectively.An equivalent scaled-down model was made to test the forces at the lever under 0,5,10,20 and 30 kg bearing weights to verify the performance of the aid.Results The trend of the tensile force exerted on the lever under five sets of different loads was in accordance with the results of the theoretical analysis.Conclusion The lifting aid with easy operation ensures patient safety and enhances the loading and unloading efficiency while saving the workload.[Chinese Medical Equipment Journal,2024,45(4):111-115]
5.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
6.A comparison of neuroendoscopic minimally invasive surgery and traditional extraventricular drainage for severe hypertensive intraventricular hemorrhage:a single-center retrospective study
Xian XIAO ; Jiayi SUN ; Qijun YUAN ; Fang XU ; Kun LU ; Haihui LIANG ; Zhipeng CHEN ; Songqing WANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(3):300-303
Objective To analyze the safety and efficacy of neuroendoscopic minimally invasive surgery and traditional extraventricular drainage in the treatment of severe hypertensive intraventricular hemorrhage.Methods The clinical data of 50 cases with neuroendoscopic ventricular hematoma evacuation(endoscopy group)and 44 cases with traditional ventricles external puncture drainage(drainage group)from July 2020 to July 2023 were retrospectively analyzed,and the hematoma clearance rates,classification of activities of daily living(ADL)scale,incidence of hydrocephalus,secondary bleeding,intracranial infection,and pulmonary infection were observed between the two groups of patients.Results After surgery,the proportion of patients with hematoma clearance rate>60%and ADL grades Ⅰ,Ⅱ,and Ⅲ in the endoscopy group were significantly higher than those in the drainage group[the proportion of patients with hematoma clearance rate>60%:88.0%(44/50)vs.47.7%(21/44),χ2=17.794,P<0.001;the proportion of individuals with ADL grades Ⅰ,Ⅱ,and Ⅲ:94.0%(47/50)vs.77.3%(33/44),respectively,χ2=5.459,P=0.019],the incidence of complications in endoscopy group was significantly lower in the drainage group[8.0%(4/50)vs.34.1%(15/44),χ2=9.879,P=0.002].Conclusion Compared with traditional ventricular puncture drainage surgery,neuroendoscopic minimally invasive surgery for the treatment of severe hypertensive intracerebral hemorrhage with ventricular casting can achieve better treatment outcomes,a higher hematoma clearance rate,and fewer postoperative complications.
7.Downregulation of MUC1 Inhibits Proliferation and Promotes Apoptosis by Inactivating NF-κB Signaling Pathway in Human Nasopharyngeal Carcinoma
Shou-Wu WU ; Shao-Kun LIN ; Zhong-Zhu NIAN ; Xin-Wen WANG ; Wei-Nian LIN ; Li-Ming ZHUANG ; Zhi-Sheng WU ; Zhi-Wei HUANG ; A-Min WANG ; Ni-Li GAO ; Jia-Wen CHEN ; Wen-Ting YUAN ; Kai-Xian LU ; Jun LIAO
Progress in Biochemistry and Biophysics 2024;51(9):2182-2193
ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.
8.Exercise Improves Nonalcoholic Fatty Liver Disease in T2DM Mice by Inhibiting Ferroptosis Through p38 MAPK Signaling Pathway
Bao-Wen ZHANG ; Ying LI ; Yuan GAO ; Ke-Yan SHENG ; Zhi WANG ; Xian-Juan KOU
Progress in Biochemistry and Biophysics 2024;51(11):2983-2997
ObjectiveTo explore the mechanism of treadmill exercise against type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) based on the regulator effects of exercise on ferroptosis. MethodsEight 8-week-old male m/m mice were used as control group (Con, n=8), and db/db mice of the matched age were randomly divided into T2DM model group (db/db, n=8), exercise group (db+Exe, n=8), p38 mitogen-activated protein kinase (MAPK) inhibitor group (db+SB203580, n=8) and exercise combined with p38 MAPK inhibitor group (db+Exe+SB203580, n=8). After one-week adaptive feeding, the mice in the db+Exe group and db+Exe+SB203580 group underwent moderate intensity treadmill exercise for 40 min/d, 5 d/week lasting 8 weeks. The db+SB203580 group and db+Exe+SB203580 group were treated with SB203580 (a specific inhibitor of p38 MAPK) with a dose of 5 mg/kg, 5 d/week for 8 weeks. And the exercise intervention was performed 2 h later after the intraperitoneal injection of SB203580. The body weight and fasting blood glucose of mice were measured regularly every week during the experiment. After 24 h of the last intervention, the mice were weighted, the liver tissues were taken, weighted and the liver index was calculated. The pathological changes of liver were determined by Oil Red O and hematoxylin-eosin (HE) staining. The levels of blood lipids, liver function, Fe2+ and oxidative stress markers of liver were measured by enzyme linked immunosorbent assay (ELISA). The related mRNA expression levels of lipogenesis and inflammation were evaluated by quantitative reverse transcriptase-mediated PCR (qRT-PCR). The related protein expression levels of lipogenesis and ferroptosis in liver were determined by immunohistochemical (IHC) staining and Western blot. ResultsThe body weight, fasting blood glucose, liver index, blood lipid and transaminase levels in the db/db group were significantly increased compared with the Con group. HE and Oil Red O staining showed severe lipid accumulation and ballooning change in the liver of db/db mice. Biochemical tests showed that Fe2+ and MDA level of liver constitution homogenate increased, while GSH level decreased significantly. The results of qRT-PCR showed that the mRNA levels of MCP-1, IL-6, SREBF1 and ACC1 in liver tissue of db/db mice were all significantly increased. Western blot results showed that the expression levels of SREBF1, ACC1 increased, ferroptosis relative proteins were significantly decreased. The 8 weeks of exercise significantly reduced the rise in body weight, blood glucose, liver index and blood lipid levels in db/db mice. Exercise intervention also alleviated hepatic steatosis and reduced the expression levels of Fe2+, MDA, MCP-1, IL-6, ACC1 and SREBF1, upregulated the expression levels of GSH, NRF2, HO-1, SLC7A11 and GPX4 in liver tissue of db/db mice. The intervention of exercise combined with SB203580 significantly down-regulated the mRNA expression levels of ACC1, MCP-1, IL-6, reduced the levels of Fe2+ and MDA, and up-regulated the level of GSH in db/db mice. Compared with the db+Exe group, the expression of Fe2+, MDA, MCP-1, and SREBF1 in the liver of the db+Exe+SB203580 group mice significantly increased, while the expression level of GSH and expression levels of ferroptosis relative proteins also significantly decreased. In addition, compared with db+SB203580 group, the iron accumulation and lipid peroxidation in the liver of db+Exe+SB203580 group were significantly improved. ConclusionThe8-week treadmill exercise can effectively alleviate liver injury and steatosis, and its mechanism may be related to the inhibition of hepatocyte ferroptosis through p38 MAPK signal.
9.Analyzing the impact of electroacupuncture on the structure and function of gut microbiota by using microbiota-derived extracellular vesicles in high-fat diet-induced obesity mice
Xian-Yun WANG ; Yuan-Cheng SI ; Lu-Qi GAO ; Zhi-Ju LI ; Zhao-Xia KANG
Parenteral & Enteral Nutrition 2024;31(2):65-72
Objective:To explore the effects of electroacupuncture in regulating the intestinal flora of high-fat diet (HFD)-fed mice from microbiota-derived extracellular vesicles. Methods:Obese mice with established nutritional obesity model were randomly divided into either the model group (n=10) or the electroacupuncture group (n=10). Acupuncture groups were chosen to pinprick points of Zhongwan, Guanyuan, Tianshu and Zusanli. Stool samples were collected from groups at the end of the intervention and extracellular vesicles (EVs) were isolated using ultracentrifugation. The morphology of EVs isolated from the stool was confirmed by transmission electron microscopy (TEM) and analysis of the associated intestinal flora by extracting microbial DNA from them for 16S rRNA sequencing. Results:The weight and Lee's index of obese mice decreased significantly after electroacupuncture intervention treatment (P<0.01). TEM images showed that EV extracted from stools were in the form of round or oval double-membraned vesicle-like structures. The 16S rRNA sequencing analysis showed that at the phylum level, the relative abundance of Proteobacteria in the model group was significantly higher than that of the normal group (P<0.05), while the relative abundance of Frimicutes and Bacteroidetes was significantly lower than that of the normal group(P<0.05). At the genus level, expressions of Psychrobacter and Planomicrobium in the model group were significantly higher than those in the normal group (P<0.01), while expressions of Solibacillus, Solibacillus, Proteus, Lactobacillus, Agrobacterium, Enterobacter, Brevundimonas, and Comamonas were significantly lower than those in the normal group (P<0.05). After electroacupuncture intervention, the intestinal microbial diversity of experimental mice increased, and the flora structure was closer to that of normal mice. Conclusion:Structural changes in the gut flora of nutritionally obese mice accompanied by changes in gut microbial-derived EVs profiles, and 16S rRNA sequencing analysis showed that microbial DNA in gut microbial-derived EVs reflected the composition of the gut microbiota, and that electroacupuncture for the treatment of obesity was not only related to the modulation of the gut flora, but was also closely related to gut microbial-derived EVs.
10.Enzyme Linked Immunosorbent Assay and Gold Nanoparticle-based Lateral Flow Immunoassay for Rapid Detection of Deltamethrin
Pan-Pan CUI ; Gui-Xiu WANG ; Yan-Ling WU ; Zhao-Xian ZHANG ; Yuan DING ; Xiu-De HUA
Chinese Journal of Analytical Chemistry 2024;52(6):828-837,中插20-中插23
In this study,nine hybridoma cells secreting monoclonal antibodies against deltamethrin were prepared,and the monoclonal antibody 4D4E11 with best sensitivity was selected to develop indirect enzyme-linked immunosorbent assay (ic-ELISA) and gold nanoparticle-based lateral flow immunoassay (LFIA) for detection of deltamethrin. The optimal working buffer for ic-ELISA was 0.01 mol/L phosphate buffer (pH 7.4) containing 0.2 mol/L NaCl and 20% methanol,while 0.01 mol/L phosphate buffer (pH 7.4) containing 1 mol/L NaCl,5‰Tween-20 and 10%methanol for LFIA. Under the optimal conditions,the half inhibition concentration (IC50) and limit of detection (IC10) of ic-ELISA were 10.60 ng/mL and 1.43 ng/mL respectively,and the limit of detection of the developed LFIA was 0.5μg/mL. The developed ic-ELISA and LFIA showed no cross-reactivities (CRs) with eight kinds of analogues of deltamethrin,which indicated the excellent specificity of proposed immunoassays. The average recoveries of the ic-ELISA in spiked tomato,cabbage and lettuce samples were 79.8%-92.6%with relative standard deviations of 0.8%-5.5%. The detection results of LFIA were consistent with the spiked concentrations in the range of 1-5 mg/kg. Meanwhile,the results of ic-ELISA and LFIA showed close correlation with high performance liquid chromatography (HPLC) in the test of blind lettuce samples. The experimental results demonstrated that the two immunoassays proposed here were suitable for rapid detection of deltamethrin with high sensitivity and high accuracy.

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