1.Extracellular vesicles: Roles in oocytes and emerging therapeutic opportunities.
Zhongyu ZHAO ; Yinrui SUN ; Renhao GUO ; Junzhi LIANG ; Wanlin DAI ; Yutao JIANG ; Yafan YU ; Yuexin YU ; Lixia HE ; Da LI
Chinese Medical Journal 2025;138(9):1050-1060
The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
Humans
;
Extracellular Vesicles/physiology*
;
Oocytes/cytology*
;
Female
;
Animals
;
Cell Communication/physiology*
2.Crosstalk and the progression of hepatocellular carcinoma.
Lei-Rong GU ; Hui ZHANG ; Juan CHEN ; Sheng-Tao CHENG
Acta Physiologica Sinica 2025;77(2):267-276
Malignant proliferating liver cancer cells possess the ability to detect and respond to various body signals, thereby facilitating tumor growth, invasion, and metastasis. One crucial mechanism through which hepatocellular carcinoma (HCC) cells interpret these signals is crosstalk. Within liver cancer tissues, cancer cells engage in communication with hepatic stellate cells (HSCs), tumor-associated macrophages (TAMs), and immune cells. This interaction plays a pivotal role in regulating the proliferation, invasion, and metastasis of HCC cells. Crosstalk occurs in multiple ways, each characterized by distinct functions. Its molecular mechanisms primarily involve regulating immune cell functions through the expression of specific receptors, such as CD24 and CD47, modulating cell functions by secreting cytokines like transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), and mediating cell growth and proliferation by activating pathways such as Wnt/β-catenin and Hedgehog. A comprehensive understanding of the mechanisms and interactions within crosstalk is essential for unraveling the pathogenesis of HCC. It also opens up new avenues for the development of innovative therapeutic strategies. This article reviews the relationship between crosstalk and the progression of HCC, offering insights and inspiration for future research.
Humans
;
Carcinoma, Hepatocellular/metabolism*
;
Liver Neoplasms/metabolism*
;
Hepatic Stellate Cells/physiology*
;
Disease Progression
;
Signal Transduction/physiology*
;
Transforming Growth Factor beta/metabolism*
;
Cell Proliferation
;
Hedgehog Proteins/metabolism*
;
Tumor-Associated Macrophages
;
Platelet-Derived Growth Factor/metabolism*
;
Cell Communication/physiology*
3.Research progress on the role of extracellular vesicles in the repair of skeletal muscle membrane injury.
Acta Physiologica Sinica 2025;77(5):956-968
The timely and efficient repair of the plasma membrane in skeletal muscle cells following injury is critical for maintaining cellular function and tissue integrity. Extracellular vesicles (EVs) play a pivotal role in this process through multi-level mechanisms. This review systematically summarizes the generation, secretion, and multifunctional roles of EVs in the repair of skeletal muscle plasma membrane damage: (1) removing damaged membrane fragments and cellular debris via endocytosis and exocytosis to maintain plasma membrane stability; (2) fusing with the injured plasma membrane to supply essential components for membrane repair and restore membrane integrity; and (3) serving as a vital mediator of intercellular communication, transmitting repair signals, promoting intercellular interactions, and orchestrating multi-level responses to facilitate tissue regeneration and functional recovery. Additionally, this article explores the potential applications of EVs in the treatment of exercise-induced injuries and muscular diseases, aiming to provide theoretical insights and novel strategies for future research and EV-based therapeutic approaches.
Extracellular Vesicles/physiology*
;
Humans
;
Muscle, Skeletal/physiology*
;
Cell Membrane/physiology*
;
Animals
;
Regeneration/physiology*
;
Exocytosis/physiology*
;
Endocytosis/physiology*
;
Cell Communication/physiology*
4.Single-cell transcriptomic analysis reveals immune dysregula-tion and macrophage reprogramming in diabetic foot ulcers.
Chunli HUANG ; Yu JIANG ; Wei JIAO ; Ying SUI ; Chunlei WANG ; Yongtao SU
Journal of Zhejiang University. Medical sciences 2025;54(5):602-610
OBJECTIVES:
To elucidate the underlying mechanisms of macrophage-mediated inflammation and tissue injury in diabetic foot ulcer (DFU).
METHODS:
Skin tissue samples were collected from patients with DFU and with non-DFU. A total of 79 272 high-quality cell transcriptomes were obtained using single-cell RNA sequencing. An unbiased clustering approach was employed to identify cell subpopulations. Seurat functions were used to identify differentially expressed genes between DFU and non-DFU groups, and gene ontology (GO) enrichment analysis was used to reveal gene function. Furthermore, cell-cell communication network construction and ligand-receptor interaction analysis were performed to reveal the mechanisms underlying cellular interactions and signaling regulation in the DFU microenvironment from multiple perspectives.
RESULTS:
The results revealed a significant expansion of myeloid cells in DFU tissues, alongside a marked reduction in structural cells such as endothelial cells, epithelial cells, and smooth muscle cells. Major cell types underwent functional reprogramming, characterized by immune activation and impaired tissue remodeling. Specifically, macrophages in DFU skin tissues exhibited a shift toward a pro-inflammatory M1 phenotype, with upregulation of genes associated with inflammation and oxidative stress. Cell communication analysis further demonstrated that M1 macrophages served as both primary signal receivers and influencers in the COMPLEMENT pathway mediated communication network, and as key signal senders and mediators in the secreted phosphoprotein 1 (SPP1) pathway mediated communication network, actively shaping the inflammatory microenvironment. Key ligand-receptor interactions driving macrophage signaling were identified, including C3-(ITGAM+ITGB2) and SPP1-CD44.
CONCLUSIONS
This study establishes a comprehensive single-cell atlas of DFU, revealing the role of macrophage-driven cellular networks in chronic inflammation and impaired healing. These findings may offer potential novel therapeutic targets for DFU treatment.
Humans
;
Macrophages/immunology*
;
Diabetic Foot/pathology*
;
Single-Cell Analysis
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Transcriptome
;
Gene Expression Profiling
;
Inflammation
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Skin
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Cell Communication
;
Signal Transduction
;
Cellular Reprogramming
5.Crosstalk between Tumor Cells and Neural Signals in Neuroendocrine Carcinoma Metastasis: Communication Hijacking Based Perspective.
Shuping SONG ; Xinyi WANG ; Siqi ZHOU ; Xuchen CHENG ; Weixuan LIN ; Yongxuan WANG ; Yanqin SUN
Chinese Journal of Lung Cancer 2025;28(2):138-145
Neuroendocrine carcinoma (NEC) represents a category of malignant tumors originating from neuroendocrine cells. Given that NEC cells exhibit characteristics of both neural and endocrine cells, they can hijack neuronal signaling pathways and dynamically regulate the expression of neuronal lineage markers during tumor metastasis, thereby constructing a microenvironment conducive to tumor growth and metastasis. Conversely, alterations in the tumor microenvironment can enhance the interactions between neurons and tumor cells, ultimately synergistically promoting the metastasis of NEC. This review highlights recent advancements in the field of cancer neuroscience, uncovering neuronal lineage markers in NEC that facilitate tumor dissemination through mediating crosstalk, bidirectional communication, and synergistic interactions between tumor cells and the nervous system. Consequently, the latest findings in tumor neuroscience have enriched our understanding of the biological mechanisms underlying tumor metastasis, opening new research avenues for a deeper comprehension of the complex biological processes involved in tumor metastasis, particularly brain metastasis. This review provides a comprehensive review of the crosstalk between tumor cells and neural signaling in the metastasis of NEC.
.
Humans
;
Carcinoma, Neuroendocrine/metabolism*
;
Signal Transduction
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Animals
;
Neoplasm Metastasis
;
Neurons/pathology*
;
Tumor Microenvironment
;
Cell Communication
6.The role of Staphylococcus aureus in the occurrence and development of chronic rhinosinusitis with nasal polyps.
Jun NEI ; Yuhuang WU ; Youqin DU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(7):679-685
Chronic rhinosinusitis with nasal polyps(CRSwNP) represents a prevalent inflammatory disorder, which is often accompanied by nasal congestion, mucopurulent discharge, olfactory dysfunction, dizziness, and headache. Staphylococcus aureus(SA), a predominant opportunistic pathogen within the sinonasal microenvironment, has been implicated in modulating the pathogenesis and progression of CRSwNP through multifaceted mechanisms. The physiological activities of SA-dependent quorum-sensing system and biofilm in the nasal microenvironment, including interactions with host, fungi, viruses, and other bacteria, as well as the effects of important superantigens secreted by SA on the microenvironment and immune barrier, are briefly reviewed in this article. These insights provide theoretical foundations for elucidating CRSwNP mechanisms and advancing clinical therapeutic strategies.
Humans
;
Sinusitis/microbiology*
;
Nasal Polyps/microbiology*
;
Staphylococcus aureus
;
Chronic Disease
;
Rhinitis/microbiology*
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Staphylococcal Infections/microbiology*
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Quorum Sensing
;
Biofilms
;
Rhinosinusitis
7.Acyl homoserine lactones facilitate the isolation and cultivation of Gram-negative bacteria from mouse intestine.
Changyu WANG ; Qinghua ZHAO ; Chang LIU ; Shuangjiang LIU
Chinese Journal of Biotechnology 2025;41(6):2349-2359
N-dodecanoyl-l-homoserine lactone (C12-HSL) is a signaling molecule that mediates bacterial quorum sensing, regulating bacterial population behaviors. This study investigated the effects of C12-HSL on the isolation and cultivation of gut microbiota, with the goal of enriching the diversity and number of cultivable bacterial strains from the mouse gut microbiota. Using a culture medium supplemented with C12-HSL, we isolated and cultivated bacterial strains from mouse intestinal contents, obtaining a total of 235 isolates. Preliminary identification based on the 16S rRNA gene revealed 54 bacterial species, including 4 potential new species, 4 potential new genera and 1 potential new family. Compared with the previously established mouse gut microbial biobank (mGMB), this study newly identified 42 bacterial species, enhancing the diversity of the strain library. Statistical analysis showed that the proportion of Gram-negative bacteria, particularly those belonging to Proteobacteria, isolated by this method was significantly higher than that obtained by conventional isolation and cultivation methods without the addition of C12-HSL. Subsequent cultivation experiments with one of the newly discovered bacterial species indicated that exogenous C12-HSL at 20-200 μmol/L significantly promoted the growth of this species, while higher concentrations of C12-HSL significantly reduced the cell density of this bacterium. This work confirms that quorum sensing molecules, such as C12-HSL, can enhance the growth, isolation, and cultivation of Gram-negative bacteria in the gut within a specific concentration range. Although the mechanism by which C12-HSL promotes the growth of gut bacterial strains requires further investigation, the findings of this study provide new insights into the targeted isolation, cultivation, and regulation of gut microbiota using bacterial quorum sensing signal molecules.
Animals
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Mice
;
Acyl-Butyrolactones/pharmacology*
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Gastrointestinal Microbiome/drug effects*
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Quorum Sensing
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Gram-Negative Bacteria/classification*
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Intestines/microbiology*
;
RNA, Ribosomal, 16S/genetics*
;
Culture Media
8.Shewanella biofilm formation regulated by acyl-homoserine lactones and its application in UO22+ electrosorption.
Tingting LIU ; Hong SHU ; Qian LI ; Zhao CUI ; Guangyue LI ; Ting LI ; Yongdong WANG ; Jing SUN
Chinese Journal of Biotechnology 2025;41(8):3081-3097
Shewanella oneidensis MR-1, a Gram-negative bacterium with a significant role in the adsorption and reduction of uranium in wastewater and a quorum-sensing effect, can be used to remove uranium from wastewater. Exogenous signaling molecules (acyl-homoserine lactones, AHLs) can be added to induce the quorum sensing behavior for rapid biofilm formation, thereby improving the removal efficiency of this bacterium for uranium. Extracellular polymeric substances (EPS), as the significant components of biofilm, play a key role in biofilm formation. To investigate the quorum sensing behavior induced by AHLs, we systematically investigated the effects of AHLs on the EPS secretion and biofilm properties of S. oneidensis MR-1 by regulating parameters such as AHL species, concentration, addition time point, and contact time. The results showed that the addition of 10 μmol/L N-butyryl-l-homoserine lactone (C4-HSL) after 6 h of culture and continued incubation to reach the time point of 72 h significantly promoted the secretion of EPSs, in which the content of extracellular proteins and extracellular polysaccharides was increased by 15.2% and 28.2%, respectively, compared with that of the control group. The biofilm electrodes induced by signaling molecules showed superior properties, which were evidenced by an increase of exceeding 20 μm in biofilm thickness, an increase of 33.9% in the proportion of living cells, enhanced electroactivity, and an increase of 10.7% in the uranium removal rate. The biofilm electrode was confirmed to immobilize uranium in wastewater mainly by electrosorption, physicochemical adsorption, and electro-reduction through characterization means such as X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). This study provides a new technical idea for the efficient recovery of uranium in wastewater and enriches the theoretical system of quorum sensing regulation of electroactive biofilms.
Biofilms/drug effects*
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Acyl-Butyrolactones/pharmacology*
;
Quorum Sensing/drug effects*
;
Uranium/metabolism*
;
Shewanella/metabolism*
;
Adsorption
;
Uranium Compounds/metabolism*
;
Wastewater/chemistry*
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Biodegradation, Environmental
;
Extracellular Polymeric Substance Matrix/metabolism*
9.Emerging roles of exosomes in oral diseases progression.
Jiayi WANG ; Junjun JING ; Chenchen ZHOU ; Yi FAN
International Journal of Oral Science 2024;16(1):4-4
Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine. Exosomes, which are characterized as nanometer-sized extracellular vesicles, are secreted by virtually all types of cells. As the research continues, the complex roles of these intracellular-derived extracellular vesicles in biological processes have gradually unfolded. Exosomes have attracted attention as valuable diagnostic and therapeutic tools for their ability to transfer abundant biological cargos and their intricate involvement in multiple cellular functions. In this review, we provide an overview of the recent applications of exosomes within the field of oral diseases, focusing on inflammation-related bone diseases and oral squamous cell carcinomas. We characterize the exosome alterations and demonstrate their potential applications as biomarkers for early diagnosis, highlighting their roles as indicators in multiple oral diseases. We also summarize the promising applications of exosomes in targeted therapy and proposed future directions for the use of exosomes in clinical treatment.
Humans
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Exosomes
;
Quality of Life
;
Extracellular Vesicles
;
Biomarkers
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Cell Communication
;
Mouth Neoplasms
10.Pathophysiological implications of cellular senescence and prospects for novel anti-aging drugs.
Acta Physiologica Sinica 2023;75(6):847-863
Chronological aging is the leading risk factor for human diseases, while aging at the cellular level, namely cellular senescence, is the fundamental driving force of organismal aging. The impact of cellular senescence on various life processes, including normal physiology, organismal aging and the progress of various age-related pathologies, has been largely ignored for a long time. However, with recent advancement in relevant fields, cellular senescence has become the core of aging biology and geriatric medicine. Although senescent cells play important roles in physiological processes including tissue repair, wound healing, and embryonic development, they can also contribute to tissue dysfunction, organ degeneration and various pathological conditions during adulthood. Senescent cells exert paracrine effects on neighboring cells in tissue microenvironments by developing a senescence-associated secretory phenotype, thus maintaining long-term and active intercellular communications that ultimately results in multiple pathophysiological effects. This is regarded as one of the most important discoveries in life science of this century. Notably, selective elimination of senescent cells through inducing their apoptosis or specifically inhibiting the senescence-associated secretory phenotype has shown remarkable potential in preclinical and clinical interventions of aging and age-related diseases. This reinforces the belief that senescent cells are the key drug target to alleviate various aging syndromes. However, senescent cells exhibit heterogeneity in terms of form, function and tissue distribution, and even differ among species, which presents a challenge for the translation of significant research achievements to clinical practice in future. This article reviews and discusses the characteristics of senescent cells, current targeting strategies and future trends, providing useful and valuable references for the rapidly blooming aging biology and geriatric medicine.
Humans
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Adult
;
Aged
;
Cellular Senescence/genetics*
;
Aging
;
Apoptosis
;
Cell Communication
;
Wound Healing/physiology*

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