1.Regulatory Mechanism of Extracellular Vesicles in The Tumor Immune Microenvironment and Its Application in Diagnosis and Treatment
Zi-Qi WANG ; Jing WANG ; Yuan-Yu HUANG ; Mei LU
Progress in Biochemistry and Biophysics 2026;53(4):968-981
Extracellular vesicles (EVs) are pivotal mediators of intercellular communication within the tumor immune microenvironment (TME). They are broadly categorized into exosomes, microvesicles, and apoptotic bodies based on their distinct biogenesis pathways. Exosomes originate from the endosomal system via multivesicular body fusion, microvesicles bud directly from the plasma membrane, and apoptotic bodies are released during programmed cell death. By shuttling diverse bioactive cargoes—including proteins, lipids, and nucleic acids such as mRNA, miRNA, and DNA—EVs exert dual modulatory effects on tumor initiation, progression, and immune evasion. Importantly, EVs exhibit remarkable compositional heterogeneity that is intrinsically linked to their cellular origin. Tumor-derived EVs (TDEVs) are typically enriched with immunosuppressive molecules like PD-L1, TGF‑β, and miR-21, which promote tumor immune escape and metastasis. In contrast, EVs derived from immune cells, such as dendritic cells or cytotoxic T lymphocytes, often carry immunostimulatory components including antigens, co-stimulatory molecules, and granzymes, thereby potentiating anti-tumor immunity. This review systematically delineates the biogenesis and molecular composition of EVs, with a particular emphasis on their dynamic regulatory functions within the TME. Specifically, we discuss how EVs mediate intricate crosstalk between immune and tumor cells, facilitating signal transfer that reshapes immune surveillance. For instance, TDEVs can induce macrophage polarization toward an M2-like pro-tumor phenotype, while also suppressing natural killer cell cytotoxicity and dendritic cell maturation. The clinical utility of EV-associated biomarkers in liquid biopsy is increasingly recognized. Circulating EVs carry tumor-specific molecular signatures that mirror the genetic and proteomic alterations of primary tumors, enabling non-invasive early diagnosis, molecular subtyping, and real-time monitoring of therapeutic responses. Their natural biocompatibility, low immunogenicity, and intrinsic ability to traverse biological barriers make them ideal candidates for drug delivery systems. This review explores cutting-edge applications, including the use of EVs in immune checkpoint blockade therapy—for instance, engineered EVs displaying anti-PD-1 antibodies or carrying siRNA to silence immunosuppressive genes. Moreover, EV-based tumor vaccines are being developed, leveraging dendritic cell-derived EVs loaded with tumor antigens to elicit potent T cell responses. The feasibility of loading EVs with therapeutic molecules such as chemotherapeutic agents, oncolytic viruses, or CRISPR-Cas9 components is also under active investigation. The advent of engineered EVs has further expanded their therapeutic potential. Through surface modification or cargo encapsulation, EVs can be tailored for targeted delivery and controlled release, enhancing precision immunotherapy. However, several hurdles impede clinical translation. Current isolation and purification methods, such as ultracentrifugation and size-exclusion chromatography, suffer from low yield and purity. Distinguishing EV subpopulations remains technically challenging due to overlapping size and marker expression. Moreover, the lack of standardized protocols for EV production, characterization, and quality control poses significant barriers to regulatory approval and clinical adoption. Looking forward, the convergence of multi-omics technologies with artificial intelligence offers a powerful approach to decipher EV heterogeneity and identify robust diagnostic signatures. Machine learning algorithms can integrate proteomic, transcriptomic, and lipidomic data from large patient cohorts to construct predictive models for cancer diagnosis and prognosis. Concurrently, advances in bioengineering are enabling the design of next-generation EVs with enhanced targeting specificity, on-demand drug release, and reduced off-target effects. Future efforts should also focus on establishing good manufacturing practice (GMP)‑compliant production processes and conducting rigorous preclinical and clinical evaluations. In summary, this review provides a comprehensive overview of EV biology, their multifaceted roles in the TME, and their transformative potential in cancer diagnostics and therapeutics. By addressing current challenges and leveraging emerging technologies, EV-based strategies are poised to revolutionize precision oncology.
2.Exploring Pathogenesis and Treatment Principles of Chronic Obstructive Pulmonary Disease Based on Spleen-mitochondria Correlation
Shiyi WANG ; Miao YU ; Xinyao HE ; Zi WANG ; Haijun LUAN ; Yibo SUN ; Haotong WANG ; Linlin WANG ; Lijian PANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):258-264
According to the Qi-blood-body fluid theory and the association between the spleen in visceral manifestation theory of traditional Chinese medicine (TCM) and mitochondria in modern cellular biology, it is proposed that the role of the spleen in generating and transforming Qi and blood is analogous to the energy-producing function of mitochondria—both serving as fundamental power sources for vital activities of the human body. The spleen governs transportation and transformation, playing a critical role in energy metabolism and the digestion and absorption of nutrients. Similarly, mitochondria are vital for maintaining physiological functions such as cellular energy supply, cell survival, and overall human metabolism. Furthermore, spleen deficiency is closely linked to mitochondrial dysfunction. Accordingly, mitochondrial energy conversion and substance metabolism are regarded as the microscopic essence of the spleen's function in transportation and transformation. Spleen deficiency and mitochondrial dysfunction contribute to the formation of pathological products such as phlegm-turbidity and blood stasis. This aligns with the pathogenesis of chronic obstructive pulmonary disease (COPD), with Qi deficiency as the root cause and phlegm-turbidity and blood stasis as the manifestations. Therefore, the integrative treatment of COPD should follow the therapeutic principle of invigorating the spleen and reinforcing healthy Qi, while also resolving phlegm and removing blood stasis to address both root cause and manifestations. This approach can improve the mitochondrial function, regulate energy metabolism, and reduce oxidative stress levels to alleviate COPD symptoms, slow down disease progression, and improve prognosis. By integrating the holistic concept of TCM with molecular mechanisms of modern medicine, this paper explores the pathogenesis and therapeutic principles of COPD from the spleen-mitochondria correlation. It not only provides a new direction for the modern development of TCM and the integration of Chinese and Western medicine but also offers a theoretical foundation for the integrated treatment of chronic, complex age-related diseases.
3.Exploring Pathogenesis and Treatment Principles of Chronic Obstructive Pulmonary Disease Based on Spleen-mitochondria Correlation
Shiyi WANG ; Miao YU ; Xinyao HE ; Zi WANG ; Haijun LUAN ; Yibo SUN ; Haotong WANG ; Linlin WANG ; Lijian PANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):258-264
According to the Qi-blood-body fluid theory and the association between the spleen in visceral manifestation theory of traditional Chinese medicine (TCM) and mitochondria in modern cellular biology, it is proposed that the role of the spleen in generating and transforming Qi and blood is analogous to the energy-producing function of mitochondria—both serving as fundamental power sources for vital activities of the human body. The spleen governs transportation and transformation, playing a critical role in energy metabolism and the digestion and absorption of nutrients. Similarly, mitochondria are vital for maintaining physiological functions such as cellular energy supply, cell survival, and overall human metabolism. Furthermore, spleen deficiency is closely linked to mitochondrial dysfunction. Accordingly, mitochondrial energy conversion and substance metabolism are regarded as the microscopic essence of the spleen's function in transportation and transformation. Spleen deficiency and mitochondrial dysfunction contribute to the formation of pathological products such as phlegm-turbidity and blood stasis. This aligns with the pathogenesis of chronic obstructive pulmonary disease (COPD), with Qi deficiency as the root cause and phlegm-turbidity and blood stasis as the manifestations. Therefore, the integrative treatment of COPD should follow the therapeutic principle of invigorating the spleen and reinforcing healthy Qi, while also resolving phlegm and removing blood stasis to address both root cause and manifestations. This approach can improve the mitochondrial function, regulate energy metabolism, and reduce oxidative stress levels to alleviate COPD symptoms, slow down disease progression, and improve prognosis. By integrating the holistic concept of TCM with molecular mechanisms of modern medicine, this paper explores the pathogenesis and therapeutic principles of COPD from the spleen-mitochondria correlation. It not only provides a new direction for the modern development of TCM and the integration of Chinese and Western medicine but also offers a theoretical foundation for the integrated treatment of chronic, complex age-related diseases.
4.Insights on Peripheral Blood Biomarkers for Parkinson’s Disease
Yu-Meng LI ; Jing-Kai LIU ; Zi-Xuan CHEN ; Yu-Lin DENG
Progress in Biochemistry and Biophysics 2025;52(1):72-87
Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α‑synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.
5.Urease-powered micro/nanomotors:Current progress and challenges
Wen-Wen LI ; Zi-Li YU ; Jun JIA
Journal of Pharmaceutical Analysis 2025;15(3):547-563
Enzyme-powered micro/nanomotors(MNMs)(EMNMs)use natural enzymes to facilitate the decom-position of fuels,including hydrogen peroxide(H2O2),glucose,triglycerides,and urea to provide power.EMNMs can achieve self-propulsion through the in situ utilization of biofuels without additional fuels,exhibiting excellent biocompatibility and significant potential for application in the biomedical field.Compared with H2O2,which may cause oxidative damage to the body,urea exhibits superior biosafety characteristics.Presently,urease-powered MNMs(UMNMs)have made notable progress in their appli-cations in the biomedical field and have garnered considerable attention from researchers.In this review,we present the latest advancements in the biomedical field of UMNMs,primarily focusing on:1)diverse materials used for constructing the fundamental framework of motors;2)control of motor movement through the regulation of enzymatic reaction rates;and 3)research directions for the clinical application of motors,including in vivo imaging,biomarker detection,cancer treatment,optical therapy,overcoming biological barriers,antibacterial interventions,antithrombotic strategies,and gastric disease manage-ment.Despite showing immense potential in biomedical applications,there are still several challenges impeding its practical implementation,such as maintaining activity in the in vivo environment while accurately targeting specific sites to achieve the desired clinical therapeutic effects.
6.Clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period
Yu WANG ; Hui-yong ZHANG ; Lin-jin CHEN ; Zheng-yi ZHANG ; Cui LI ; Jie CUI ; Ben SU ; Ping BAI ; Zi-feng MA ; Zhen-hui LU
Chinese Traditional Patent Medicine 2025;47(1):81-86
AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1%,PEF%),inflammatory indices(EOS,EOS%,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P<0.05),and decreased TCM syndrome score(P<0.05),especially for the observation group(P<0.05);the observation group exhibited increased FEV1,FEV1%,PEF%(P<0.05),among which FEV1,PEF%were higher than those in the control group(P<0.05);the observation group showed decreased inflammatory indices(P<0.05),among which FeNO was lower than that in the control group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.
7.Study of debridement effects of multi shapes of plasma scalpels in explosion injury model
Hong-ye ZHENG ; Yu LI ; Zi-heng XU ; Yu-fan WEI ; Bo-ya ZHANG ; Yan LI ; Li ZHU ; Xi-ru LI
Chinese Medical Equipment Journal 2025;46(2):31-38
Objective To explore the debridement effects of 3 types of plasma scalpels for the animal model of explosion injury,and to compare them with the steel scalpel and high-frequency electrosurgical scalpel.Methods Firstly,blast wounds were constructed in the right inguinal regions of 9 Landrace pigs by high-pressure gas impact combined with preset metal shrapnel.Secondly,debridement was carried out in experimental groups with wide-,arrow-or needle-type plasma scalpel and in control groups with steel and high-frequency electrisurgical scalpel,with the operating temperature and debridement time recorded during the procedure and trauma specimens analyzed pathologically after the debridement;comparisons were performed among the five types of scalpels in terms of debridement effect,and among the four ones in terms of maximum operating temperature and depth of tissue thermal damage under electrocutaneous cutting and electrocoagulation modes with the steel scalpel excluded because it did not generate any heat.GraphPad Prism 9.5.1 software was used for statistical analysis.Results There were no significant differences in debridement effect found between the three plasma scalpels and the steel and high-frequency electrosurgical scalpels(P>0.05).The three types of plasma scalpels had the maximum operating temperature lower significantly than that of the high-frequency electrosurgical scalpel during debridement(P<0.05).Under electrosection and electrocoagulation modes the three plasma scalpels had the depths of tissue thermal damage statistically less than that by the high-frequency electrosurgical scalpel under electrosection and electrocoagulation modes(P<0.05).The depths of tissue thermal damage by the four scalpels under electrocoagulation mode were obviously greater than those under electrosection mode(P<0.05).Conclusion Multi shapes of plasma scalpels behave well in debridement with low operating temperature,little tissue thermal damage and high efficiency for wound protection and the same efficacy with the steel scalpel and high-frequency electrosur-gical scalpel.[Chinese Medical Equipment Journal,2025,46(2):31-38]
8.Design of intelligent airborne soldier physical training system based on human body composition analysis
Lin YANG ; Zheng LIU ; Yu-shan YE ; Jian-fei PANG ; Jing HE ; Xuan-zi ZHOU ; Qiong WANG ; Xin-sheng CAO ; Tao LIU
Chinese Medical Equipment Journal 2025;46(2):16-23
Objective To design an intelligent airborne soldier physical training system based on human body composition analysis to solve the problems in diversity of training mode,targeted training plan and high incidence of military training-related injuries.Methods The intelligent airborne military physical training system was designed with B/S architecture and developed with Python language,which was composed of four functional modules for airborne soldier information acquisition,trainee physical fitness state assessment,physical fitness training program recommendation and airborne soldier physical fitness training program evaluation.The airborne soldier information acquisition module collected and analyzed the trainee physiological parameter information with a human body composition analyzer,clarified the parameter characteristics related to physical training with considerations on military physical training requirements and constructed a trainee physical fitness assessment parameter model;the trainee physical fitness state assessment module established an evaluation model based on machine learning to realize stage-by-stage physical fitness evaluation for airborne soldiers;the physical fitness training program recommendation module was constructed based on the physical training feature similarity algorithm and graph embedding theory to provide decision making assistance for program development of airborne military physical training;the airborne soldier physical fitness training program evaluation module compared the physical fitness and evaluation results before and after training by means of list and chart,and updated the training program based on the evaluation results by calling the physical training program recommendation module.Results The intelligent airborne soldier physical training system contributed to forming an individualized physical fitness training recommendation mechanism after trainee body evaluation,modifying training program based on comparison and feedback for stage-by-stage training evaluation,so as to decrease the incidence of military training-related injuries while increasing the training efficiency.Conclusion The system developed improves airborne soldier physical training in rationality and reliability,and provides references for intelligent military training of the PLA.[Chinese Medical Equipment Journal,2025,46(2):16-23]
9.Construction of a recombinant adenovirus for Mycobacterium tuberculosis c-di-AMP phosphodiesterase expression and induction of humoral immunity
Jia-hao HU ; Huan-huan NING ; Meng-juan DONG ; Yan-zhi LU ; Ting DAI ; Cong-yue ZHANG ; Zi-qing XU ; Shu-yu WANG ; Zheng-yan ZHOU ; Yin-lan BAI
Chinese Journal of Zoonoses 2025;41(4):364-369
A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.
10.Mechanism of emodin improving cardiac hypertrophy in mice based on p38/ERK pathway
Jia SHI ; Sai-Ge SUN ; Yi-Lin HE ; Li XU ; Long-Xing LIU ; Zi-Jie GE ; Xiao-Yi ZOU ; Yu MA ; Yao-Cheng DING ; Kai QIAN
Chinese Pharmacological Bulletin 2025;41(7):1245-1252
Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

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