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Mesenchymal stem cells (MSCs) are adult stromal cells with the capacity to differentiate into multiple types of cells. MSCs represent an attractive option in regenerative medicine due to their multifaceted abilities for tissue repair, immunosuppression, and anti-inflammation. Recent studies demonstrate that MSCs exert their effects via paracrine activity, which is at least partially mediated by extracellular vesicles (EVs). MSC-derived EVs (MSC-EVs) could mimic the function of parental MSCs by transferring their components such as DNA, proteins/peptides, mRNA, microRNA (miRNA), lipids, and organelles to recipient cells. In this review, we aim to summarize the mechanism and role of miRNA transfer in mediating the effects of MSC-EVs in the models of human diseases. The first three sections of the review discuss the sorting of miRNAs into EVs, uptake of EVs by target cells, and functional transfer of miRNAs via EVs. Then, we describe the composition of miRNAs in MSC-EVs. Next, we provide the existing evidence that MSC-EVs affect the outcomes of renal, liver, heart, and brain diseases by transferring their miRNA contents. In conclusion, EV-mediated miRNA transfer plays an important role in disease-modulating capacity of MSCs.

Extracellular vesicles (EVs) contain proteins, microRNAs, mRNAs, long non-coding RNAs, and phospholipids, and are a novel mechanism of intercellular communication. It has been proposed that the immunomodulatory and regenerative effects of mesenchymal stem/stromal cells (MSCs) are mainly mediated by soluble paracrine factors and MSC-derived EVs (MSC-EVs). Recent studies suggest that MSC-EVs may serve as a novel and cell-free alternative to whole-cell therapies. The focus of this review is to discuss the functional proteins which facilitate the effects of MSC-EVs. The first section of the review discusses the general functions of EV proteins. Next, we describe the proteomics of MSC-EVs as compared with their parental cells. Then, the review presents the current knowledge that protein contents of MSC-EVs play an essential role in immunomodulation and treatment of various diseases. In summary, functional protein components are at least partially responsible for disease-modulating capacity of MSC-EVs.

Background Identifying the past and future burden of kidney cancer (KC) and its temporal trends among older adults (≥ 65 years) at global, regional, and national levels is critical for effective prevention strategies. Methods The age-standardized incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated using data from the Global Burden of Disease (GBD) study from 1990 to 2021. These indicators were stratified by sex, age, and socio-demographic index (SDI). The correlation between these indicators and SDI was assessed. Temporal trends were quantified using the annual average percentage change (AAPC), and future trends from 2022 to 2040 were predicted using the Bayesian age-period-cohort (BAPC) model. Results The global age-standardized incidence rate (ASIR) of KC among older adults increased from 21.73 per 100,000 people in 1990 to 26.74 per 100,000 people in 2021, with an AAPC of 0.67%. Age-standardized DALYs rate (ASDR) remained stable, while significant increases were observed in age-standardized prevalence (AAPC = 1.24%, 95%CI: 1.14–1.34%) and mortality rate (AAPC = 0.13%, 95%CI: 0.05–0.22%). From 1990 to 2021, males consistently exhibited a higher disease burden than females, additionally, the ASIR of KC increased significantly in all age subgroups. Regions with higher SDI levels also showed a greater disease burden, while Oceania had the lowest burden of KC in 2021. The ASIR increased in almost all countries and territories. Czechia showed the highest ASIR (92.25 per 100,000 people) and ASDR (819.88 per 100,000 people). Smoking and high body mass index (BMI) remained significant risk factors for DALYs and mortality in the older population, and their effects were greatest in high SDI region. Furthermore, the burden of KC is expected to continue to decline through 2040. Conclusions The global burden of KC among older adults increased from 1990 to 2021, with notable regional and national variations. However, it is projected to continue to decline through 2040. The management of smoking and high BMI remain major challenges for people with KC, necessitating targeted clinical guidelines, particularly focusing on males and the older adults.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus to cause acute respiratory distress syndrome (ARDS) and contains four structural proteins: spike, envelope, membrane, and nucleocapsid. An increasing number of studies have demonstrated that all four structural proteins of SARS-CoV-2 are capable of causing lung injury, even without the presence of intact virus. Therefore, the topic of SARS-CoV-2 structural protein-evoked lung injury warrants more attention. In the current article, we first synopsize the structural features of SARS-CoV-2 structural proteins. Second, we discuss the mechanisms for structural protein-induced inflammatory responses in vitro . Finally, we list the findings that indicate structural proteins themselves are toxic and sufficient to induce lung injury in vivo . Recognizing mechanisms of lung injury triggered by SARS-CoV-2 structural proteins may facilitate the development of targeted modalities in treating COVID-19.

Background Traditional Chinese medicine (TCM) is an important source of bioactive compounds, hence enjoying a wide application in clinical treatment, while its pharmacodynamic material basis remains difficult to elucidate as it has a complex chemical composition. Piper longum L is a commonly used herbal medicine in prescriptions for chronic kidney disease (CKD), yet its key active ingredients responsible for anti-renal fibrosis effects remain unclear. This study aimed to establish a novel and efficient strategy for the screening and identification of anti-fibrotic compounds from Piper longum L. Methods HK-2 cells with fibrotic features induced by transforming growth factor-β (TGF-β) were used to develop a hollow fiber cell fishing coupled with high-performance liquid chromatography (HFCF-HPLC) mode. This model was integrated with network pharmacology and molecular biology techniques to screen and validate active anti-fibrotic compounds in Piper longum L. The in vivo efficacy of the identified compounds was further evaluated by a unilateral ischemia–reperfusion injury (uIRI) model with delayed contralateral nephrectomy in C57BL/6 J mice. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were taken into account to assess the renal function, while immunohistochemistry and western blot served for analyzing the fibrosis markers α-SMA and collagen-I. Results HFCF-HPLC screening identified two key active compounds from Piper longum L: piperlongumine (PIPA) and piperlonguminine (PLG). Among them, PIPA exhibited the strongest inhibitory effect on the expression of fibrosis markers in vitro. In vivo studies demonstrated that PIPA significantly reduced renal fibrosis in the uIRI model, as indicated by lower SCr and BUN levels, improved renal histopathology, and reduced extracellular matrix deposition. Conclusions A novel HFCF-HPLC model was successfully established to screen active compounds from TCM against renal fibrosis. PIPA was identified as a promising anti-fibrotic agent from Piper longum L, demonstrating significant renoprotective effects in in vitro and in vivo models. This work advances the modernization of herbal medicine research by offering a integrated strategy for identifying bioactive TCM components.

ObjectiveThis study aimed to investigate the pathways linking internship experience to psychological symptoms among Chinese healthcare trainees, with a particular focus on the mediating role of burnout.MethodsA single-center cross-sectional survey was conducted among 241 Chinese healthcare trainees at a teaching hospital. Data were collected using a self-developed Internship Experience Scale, the Maslach Burnout Inventory–Student Survey (MBI-SS), and the Symptom Checklist-90 (SCL-90). Structural equation modeling (SEM) was applied to examine the hypothesized relationships, and mediation effects were tested using bootstrap procedures.ResultsInternship experience was negatively associated with burnout, whereas burnout showed positive associations with anxiety and depression. Anxiety and depression were highly correlated, and mediation analysis confirmed burnout as a significant intermediary linking internship experience and psychological symptoms.ConclusionThis study highlights the critical role of burnout in shaping the mental health outcomes of healthcare trainees, emphasizing the need for supportive educational environments to foster resilience and well-being.

Mitochondria-associated membranes (MAMs), the specialized contact regions linking the endoplasmic reticulum (ER) and mitochondria, have emerged as dynamic communication hubs critical for preserving cellular homeostasis. These structures are crucial for controlling a range of essential cellular processes, such as calcium (Ca 2+ ) signaling, lipid metabolism, autophagy, apoptosis, and inflammatory response. Increasing evidence connects MAM dysfunction to various inflammatory conditions, such as metabolic disorders, neurodegenerative diseases, and antiviral response. In the context of acute lung injury, altered ER–mitochondria interactions can result in mitochondria Ca 2+ overload, heightened oxidative stress, and augmented inflammatory response. Together, these pathological processes enhance endothelial permeability and exacerbate pulmonary inflammation. This review highlights the structural and functional attributes of MAMs, the mechanisms underlying MAM-mediated inflammation, and the roles of MAMs in metabolic, neurological, and antiviral inflammation. It also delves into the role of MAMs in acute lung injury, unveiling fresh insights that may pave the way for innovative therapies targeting ER–mitochondria crosstalk.

Background Macrophages have heterogeneous phenotypes and complex functions within both innate and adaptive immune responses. To date, most experimental studies have been performed on macrophages derived from bone marrow, spleen and peritoneum. However, differences among macrophages from these particular sources remain unclear. In this study, the features of murine macrophages from bone marrow, spleen and peritoneum were compared. Results We found that peritoneal macrophages (PMs) appear to be more mature than bone marrow derived macrophages (BMs) and splenic macrophages (SPMs) based on their morphology and surface molecular characteristics. BMs showed the strongest capacity for both proliferation and phagocytosis among the three populations of macrophage. Under resting conditions, SPMs maintained high levels of pro-inflammatory cytokines expression (IL-6, IL-12 and TNF-α), whereas BMs produced high levels of suppressive cytokines (IL-10 and TGF-β). However, SPMs activated with LPS not only maintained higher levels of (IL-6, IL-12 and TNF-α) than BMs or PMs, but also maintained higher levels of IL-10 and TGF-β. Conclusions Our results show that BMs, SPMs and PMs are distinct populations with different biological functions, providing clues to guide their further experimental or therapeutic use.

Pan-arterial diseases, including atherosclerosis (AS), aortic aneurysm and dissection (AAD), and peripheral arterial disease (PAD), impose a substantial global health burden. Although ambient temperature has been implicated in individual arterial conditions, its association with mortality across the pan-arterial spectrum remains incompletely understood. To evaluate the association between ambient temperature and mortality from pan-arterial diseases across the United States. We analysed mortality data for adults aged ≥25 years with AS, AAD, or PAD in the United States CDC WONDER database from 1999 to 2023. Age-adjusted mortality rates (AAMR) and average annual percent change (AAPC) were estimated. Monthly air-temperature metrics (1999-2023) were linked at the United States Census region level. Seasonal variation was assessed using analysis of variance. Associations between temperature and mortality were examined using Spearman correlation, Poisson regression with lag structures, and distributed lag non-linear models (DLNM), with results expressed as relative risks (RR) per 10°F increase in temperature. Between 1999 and 2023, AAMRs declined for AS, AAD, and PAD, yet mortality burden remained substantial. Mortality from all three conditions was consistently higher in winter than in summer across Census regions. Monthly mean temperature was inversely correlated with crude mortality for pan-arterial diseases (P < 0.05). In the Northeast, cumulative RR per +10°F across lags 0-3 months was 0.919 for AS, 0.945 for AAD, and 0.953 for PAD, with similar patterns observed in other regions. DLNM analyses demonstrated a predominantly cold-related excess risk, with acute effects and regional heterogeneity at higher temperatures. Lower ambient temperatures are associated with increased mortality from pan-arterial diseases in the United States. These findings highlight shared vulnerability to cold exposure across arterial diseases and support winter-focused preventive and healthcare preparedness strategies.