1.Regulatory Effects of Exercise on The Natural Immune System and Related Molecular Mechanisms
Shu-Yang ZHAO ; Xin LI ; Ke NING ; Zhuo WANG
Progress in Biochemistry and Biophysics 2025;52(10):2535-2549
The innate immune system serves as the body’s first line of defense against pathogens and plays a central role in inflammation regulation, immune homeostasis, and tumor immunosurveillance. In recent years, with the growing recognition of the concept “exercise is medicine”, increasing attention has been paid to the immunoregulatory effects of physical activity. Accumulating evidence suggests that regular, moderate-intensity exercise significantly enhances innate immunity by strengthening the skin-mucosal barrier, increasing levels of secretory immunoglobulin A (sIgA), and improving the functional capacity of key immune cells such as natural killer (NK) cells, neutrophils, macrophages, and dendritic cells. It also modulates the complement system and various inflammatory mediators. This review comprehensively summarizes the effects of exercise on each component of the innate immune system and highlights the underlying molecular mechanisms, including activation of AMP-activated protein kinase (AMPK), inhibition of nuclear factor-kappa B (NF-κB), enhancement of mitochondrial function via the PGC-1α/TFAM axis, and initiation of autophagy through the ULK1/mTOR pathway. Emerging mechanisms are also discussed, such as exercise-induced epigenetic modifications (e.g., histone acetylation and miRNA regulation), modulation of the gut microbiota, and metabolite-mediated immune programming (e.g., short-chain fatty acids (SCFAs), β‑hydroxybutyrate). The effects of exercise on innate immunity vary considerably among individuals, depending on factors such as age, sex, and comorbidities. For example, adolescents exhibit enhanced NK cell mobilization, whereas older adults benefit from reduced chronic inflammation and immune aging. Sex hormones and metabolic conditions (e.g., obesity, diabetes, chronic obstructive pulmonary disease, cancer) further modulate the immune response to exercise. Based on these insights, we propose a personalized approach to exercise prescription guided by the FITT (frequency, intensity, time, and type) principle, aiming to optimize immune outcomes across diverse populations. Importantly, given the dual role of exercise in immune activation and regulation, caution is warranted: while moderate exercise enhances immune defense, excessive or high-intensity activity may induce transient immunosuppression. In pathological contexts such as infection, autoimmune diseases, or tissue injury, exercise intensity and timing must be carefully adjusted. This review provides practical guidelines for exercise-based immune modulation and underscores the need for dose-response studies and advancements in precision exercise medicine. In conclusion, exercise represents a safe and effective strategy for enhancing innate immune function and mitigating chronic inflammatory diseases.
2.The combination of berberine and cinnamon polyphenol can improve glucose metabolism in T2DM rats through Bas-TGR5-GLP-1
Wan LIU ; Fei LIANG ; Tie-quan CAI ; Ying LI ; Le LI ; Shu-cai YANG ; Ying LIU ; Yan ZHAO
Acta Pharmaceutica Sinica 2024;59(1):135-142
Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (
3.Clinical application and perspectives of unilateral biportal endoscopic technique
Zhen HU ; Yang YANG ; Shu-Xiong ZHAO ; Qun-Li ZHANG ; Tong-Tong ZHANG ; Lin LIU
Medical Journal of Chinese People's Liberation Army 2024;49(3):349-354
Unilateral biportal endoscopic(UBE)technique is a minimally invasive spinal technique developed rapidly in recent years.Compared with traditional spinal endoscopy,the prominent feature of UBE is that it can open two channels on the same side of the spine,which can be used to provide visual field and insert operating instruments respectively,greatly expanding the operating space and reducing the difficulty of surgery.It has the advantages of less bleeding,little injury,quick recovery and mild pain,and has unique advantages in the treatment of lumbar spinal stenosis,lumbar disc herniation and other lumbar degenerative diseases.With the continuous in-depth exploration and development of the UBE technique,the field of diseases that can be treated by this technology has gradually expanded.It is not only limited to lumbar diseases,but also has made great progress in cervical and thoracic diseases,which has attracted the attention of many spinal surgeons.UBE technique has become one of the promising surgical methods for spinal-related diseases,but there are also complications such as incomplete decompression,nerve root and dural injury,epidural hematoma,relatively prolonged operation time,operation fatigue and other deficiencies.This paper summarizes the progress of the UBE technique,discusses its complications and deficiencies,proposes relevant solutions and possible future directions for its development,so as to provide reference for the clinical practice of UBE technique.
6.Optimization of the Forming Process of Mingmu Yijing Pills Based on AHP-CRITIC Mixed Weighting Method
Chunhong YANG ; Shu LI ; Qi ZHAO ; Qian SHI ; Yanxiong GAN ; Xianrong LAI ; Rui LI
Chinese Journal of Modern Applied Pharmacy 2024;41(5):672-677
OBJECTIVE
To clarify the weight index and optimize the technology of compound Mingmu Yijing pills.
METHODS
Water content, dissolution time limit and bolus-forming pass rate were included as evaluation indexes. The analytic hierarchy process(AHP) and the criterion importance through inter-criteria correlation(CRITIC) method based on the objectivity of indicators were adopted, AHP-CRITIC mixed weighting method. In this way, the relative coefficients of each index were calculated for weight distribution and comprehensive score, and the molding process was optimized and verified by Box-Behnken response surface test.
RESULTS
Compared with the single weighting method, the AHP-CRITIC mixed weighting method was more reasonable and stable. This method finally optimized the forming process conditions of Mingmu Yijing pills as follows: adding water amount of 0.8 times, the damp mass infiltration for 0.5 h, drying temperature of 60 ℃, drying time of 8 h. The mean comprehensive score of validation experiment was 88.21, RSD was 0.29%.
CONCLUSION
AHP-CRITIC method scientifically determines the weight of multiple indicators, and the verification test confirms that the optimized molding process is stable and feasible, which can be used in practical large-scale production.
7.Role of Naoan capsules in treatment of ischemic stroke by network pharmacology combined with GEO database and molecular docking
Shu-Xian YANG ; A-Ning SUN ; Bin ZHU ; Wei-Zhong SHI ; Zhi-Gang ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(3):435-439
Objective To predict and verify the mechanism of Naoan capsules(NAC)in treatment of ischemic stroke(IS)by network pharmacology,Gene Expression Omnibus(GEO)database,and molecular docking technology.Methods The active components in NAC were collected using the Traditional Chinese Medicine System Pharmacological Analysis Platform,and the disease-related differential genes were screened using GEO database.After screening and obtaining the common targets of the two,the compound disease network was constructed by Cytoscape 3.8.2 software.At the same time,protein-protein interaction networks were created to identify candidate targets for NAC treatment of IS,and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed.Finally,core targets were verified by molecular docking technology.Results A total of 56 candidate compounds and 18 544 disease-related differential genes were screened.Further,quercetin,kaempferol,luteolin and baicalein were found to be the key active compounds of NAC in the treatment of IS through the compound disease network.In the search of PPI network core,eight key targets for NAC treatment of IS were screened,including mitogen-activated protein kinase 1(MAPK1),B-cell lymphoma factor 2(Bcl-2),cysteinylaspartate specific protease 3(CASP3),etc.In addition,the key pathways of NAC treatment of IS are mainly concentrated in lipid and atherosclerosis,advanced glycation end products and receptor for advanced glycation end products(AGE-RAGE),tumor necrosis factor(TNF),interleukin17(IL-17),C-type lectin receptor,apoptosis,hypoxia-inducing factor-1(HIF-1),MAPK and other signaling pathways.Finally,the molecular docking results showed that the key active compounds(quercetin,kaempferol,luteolin and baicalein)had good binding force with the 8 key targets,which initially verified the results of network pharmacology.Conclusion NAC plays a role in the treatment of IS through multi-component,multi-target and multi-pathway.
8.Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner
Mei Le YANG ; Qi ZHENG ; Jia Xiao LIU ; Xian Xian LI ; Lim VERONICA ; Qi CHEN ; Hua Zhong ZHAO ; Yang Shu WANG
Biomedical and Environmental Sciences 2024;37(1):71-84
Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.
9.Establishment and Application of a Duplex Real Time Fluorogenic Quantitative PCR Assay System for miR-451a and miR-21-5p
Shu-Xiao HU ; Hui-Xiang CHEN ; Sheng HU ; Yi-Xia ZHAO ; An-Quan JI ; Yang LI ; Jie LIAN ; Qi-Fan SUN
Progress in Biochemistry and Biophysics 2024;51(3):706-715
ObjectiveBody fluid stains left at crime scenes are frequently trace amounts, while the identification of body fluids through real time fluorogenic quantitative technique often necessitates the repeated detection within the limited sample, as multiple miRNA markers are the basis for the identification. Based on the goal of both the throughput and efficiency improvement of miRNA analysis in trace samples, a duplex real time fluorogenic quantitative PCR assay system was designed to accurately quantify two miRNAs simultaneously, and the system should be further verified by actual sample for the body fluid identification. MethodsThe duplex real time fluorogenic quantitative PCR system of miR-451a to miR-21-5p was established with specially designed primers and probes, and the concentrations of the primers and probes were both optimized. The specificity, sensitivity and reproducibility of the system were validated, while its capability for body fluid identification was assessed using the miR-451a to miR-21-5p ratio. ResultsThe optimized assay system exhibited excellent specificity and repeatability, with coefficients of variation consistently below 8% for both intra- and inter-batch variability. The amplification efficiency of miR-451a and miR-21-5p reached 71.77% and 74.81%, respectively, with high and relatively consistent results. By utilizing this duplex real time fluorogenic quantitative PCR assay system, a total of 58 body fluid samples were analyzed, exhibiting a discrimination rate of 100% between blood and non-blood samples, as well as between peripheral blood and menstrual blood samples. Moreover, the results, obtained from single real time fluorogenic quantitative PCR assay system and duplex real time fluorogenic quantitative PCR assay system, showed no statistically significant difference with randomly selected blood samples (n=20). Compared to previous single real time fluorogenic quantitative PCR assay system, the sensitivity of duplex real time fluorogenic quantitative PCR assay system exhibited remarkable improvement. A minimum input of only 0.1 ng total RNA was sufficient for accurate detection of peripheral blood and menstrual blood samples, while saliva, semen, and vaginal secretion required only 1 ng total RNA for precise identification purposes. Additionally, the duplex real time fluorogenic quantitative PCR assay system successfully differentiated between different types of body fluids in simulated samples under natural outdoor conditions. ConclusionThe duplex real time fluorogenic quantitative PCR assay system effectively reduced both the time and material costs by half compared to the single system, especially suitable for the examination of body fluid stains left at crime scenes, solving the contradiction between the trace amount and the multiple sample volumes demand of repeated real time fluorogenic quantitative PCR. The duplex real time fluorogenic quantitative PCR assay successfully distinguished blood and other body fluid, as well as peripheral blood and menstrual blood samples, which maintains an equivalent capability for body fluid identification with half sample, time and reagent consumption. This system provides an efficient tool for identifying suspicious body fluids, as well as a foundation for more multiplexed real time fluorogenic quantitative PCR assay system research.
10.Based on supramolecular chemistry to explore the scientific connotation of predecocting gypsum in Maxingshigan decoction preliminarily
Yao-zhi ZHANG ; Shu-chang YAO ; Lu-ping YANG ; Yi-hang ZHAO ; An-qi XU ; Xue-mei HUANG ; Peng-long WANG
Acta Pharmaceutica Sinica 2024;59(6):1828-1840
It has gradually become a consensus in the industry that the traditional Chinese medicine gypsum should be decocted first, but the understanding of decocting method is not completely unified in the works of doctors since ancient times, and there are occasional disputes about whether it is necessary to decocting first. In this study, the phase determination, physical and chemical characterization, qualitative and quantitative analysis of inorganic and organic components of the decoctions of herbal pairs and the whole prescription Maxingshigan decoction with gypsum as the center, and the pre-decoctions and co-decoctions of them were carried out to explore the scientific connotation of the pre-decoctions of gypsum. Results show that decoction phases were different between the co-decoctions and pre-decoctions of licorice-gypsum (Gancao-Shigao, GC-SG), ephedra-gypsum (Mahuang-Shigao, MH-SG) and almond-gypsum (Xingren-Shigao, XR-SG). The results of the micromorphology, particle size and zeta potential of herbal pairs and prescription (Quanfang, QF) showed that the supramolecular particles in pre-decoctions were smaller, more uniform and more stable than the co-decoctions. The results of organic components analysis showed that different cooking methods did not change the organic composition and content. ICP-OES results showed that the content of inorganic components in pre-decoctions was higher than in co-decoctions for the same boiling time of gypsum. The IR results showed that the pre-decoctions had stronger chemical functional group effect than the co-decoctions. To sum up, compared with the co-decoction, the pre-decoction of gypsum has different phase state and chemical composition interaction, and the difference of inorganic composition is an important material basis affecting the change of phase state compared with the co-decoction. It indicates that the material basis of traditional Chinese medicine decoction is indeed different whether gypsum is decocted first or not, which can provide a basis for the clinical application of decocted gypsum.


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