MedComm最新文献

Hydrogels have emerged as dependable candidates for tissue repair because of their exceptional biocompatibility and tunable mechanical properties. However, conventional hydrogels are vulnerable to damage owing to mechanical stress and environmental factors that compromise their structural integrity and reduce their lifespan. In contrast, self-healing hydrogels with their inherent ability to restore structure and function autonomously offer prolonged efficacy and enhanced appeal. These hydrogels can be engineered into innovative forms including stimulus-responsive, self-degradable, injectable, and drug-loaded variants, thereby enhancing their applicability in wound healing, drug delivery, and tissue engineering. This review summarizes the categories and mechanisms of self-healing hydrogels, along with their biomedical applications, including tissue repair, drug delivery, and biosensing. Tissue repair includes wound healing, bone-related repair, nerve repair, and cardiac repair. Additionally, we explored the challenges that self-healing hydrogels continue to face in tissue repair and presented a forward-looking perspective on their development. Consequently, it is anticipated that self-healing hydrogels will be progressively designed and developed for applications that extend beyond tissue repair to a broader range of biomedical applications.

Sudomotor dysfunction in diabetic patients increases the risk of fissures, infections, and diabetic foot ulcers (DFUs), thereby reducing the quality of life. Despite its clinical importance, the mechanisms underlying this dysfunction remain inadequately elucidated. This study addresses this gap by demonstrating that despite structural integrity, sweat glands (SGs) in diabetic individuals with DFUs, and a murine model of diabetic neuropathy (DN), exhibit functional impairments, as confirmed by histological and functional assays. Integrated transcriptome and proteome analysis revealed significant upregulation of the SG microenvironment in response to hypoxia, highlighting potential underlying pathways involved. In addition, histological staining and tissue clearing techniques provided evidence of impaired neurovascular networks adjacent to SGs. Single-cell RNA sequencing unveiled intricate intercellular communication networks among endothelial cells (ECs), neural cells (NCs), and sweat gland cells (SGCs), emphasizing intricate cellular interactions within the SG microenvironment. Furthermore, an in vitro SGC–NC interaction model (SNIM) was employed to validate the supportive role of NCs in regulating SGC functions, highlighting the neurovascular-SG axis in diabetic pathophysiology. These findings confirm the hypoxia-driven upregulation of the SG microenvironment and underscore the critical role of the neurovascular-SG axis in diabetic pathophysiology, providing insights into potential therapeutic targets for managing diabetic complications and improving patient outcomes.

From the pioneering days of cell therapy to the achievement of bioprinting organs, tissue engineering, and regenerative medicine have seen tremendous technological advancements, offering solutions for restoring damaged tissues and organs. However, only a few products and technologies have received United States Food and Drug Administration approval. This review highlights significant progress in cell therapy, extracellular vesicle-based therapy, and tissue engineering. Hematopoietic stem cell transplantation is a powerful tool for treating many diseases, especially hematological malignancies. Mesenchymal stem cells have been extensively studied. The discovery of induced pluripotent stem cells has revolutionized disease modeling and regenerative applications, paving the way for personalized medicine. Gene therapy represents an innovative approach to the treatment of genetic disorders. Additionally, extracellular vesicle-based therapies have emerged as rising stars, offering promising solutions in diagnostics, cell-free therapeutics, drug delivery, and targeted therapy. Advances in tissue engineering enable complex tissue constructs, further transforming the field. Despite these advancements, many technical, ethical, and regulatory challenges remain. This review addresses the current bottlenecks, emphasizing novel technologies and interdisciplinary research to overcome these hurdles. Standardizing practices and conducting clinical trials will balance innovation and regulation, improving patient outcomes and quality of life.

There are no effective curative treatments for Alzheimer's disease (AD), the most prevalent form of dementia. Amyloid-beta (Aβ) oligomers are considered key neurotoxic molecules that trigger AD. Recent studies have shown that direct antibody targeting of Aβ oligomers is beneficial for early AD patients; however, serious side effects (e.g., brain hemorrhage, edema, and shrinkage) persist. Considering that Aβ oligomers readily bind to other proteins, contributing to neurotoxicity and AD onset, those proteins could represent alternative therapeutic targets. However, proteins that bind to Aβ oligomers in the brains of AD patients have not yet been identified. In this study, we identified four proteins (DDX6, DSP, JUP, and HRNR) that bind to Aβ oligomers derived from the brains of AD patients. Intriguingly, among these four proteins, only the blockade of DEAD-box helicase 6 (DDX6) in human-derived Aβ oligomers attenuated their neurotoxicity both in vitro and in vivo. Mechanistic analysis revealed that DDX6 promotes the formation of Aβ oligomers, likely due to DDX6 bind to Aβ oligomers at four distinct sites. These findings suggest that DDX6 could serve as a potential therapeutic target to reduce the neurotoxicity of Aβ oligomers in the brain and prevent the progression of AD.

The emergence of coronavirus disease 2019 (COVID-19) has triggered research into its impact on male reproductive health. However, studies exploring the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on semen quality in infertile men remain limited. Herein, we enrolled 781 male infertile patients who recovered from COVID-19 and analyzed their semen and blood samples collected at different time points. We found that SARS-CoV-2 RNA was undetectable in semen samples. Compared with pre-COVID-19 status, total sperm count, sperm concentration, vitality, motility, and percentage of sperm cells with normal morphology decreased significantly in the first month post-COVID-19. However, these alterations were reversed in the third month. Furthermore, seminal plasma samples exhibited reduced proinflammatory cytokine levels and notable changes in amino acid, nucleic acid, and carbohydrate metabolism by the third month compared with those in the first month. By contrast, no significant alterations in reproductive hormone levels were found. Vitality, progressive motility, and total motility negatively correlated with body temperature when it was above 38°C. In conclusion, semen quality initially decreases post-COVID-19 but reverses after approximately 3 months, with a decline related to inflammatory and fever. These findings may provide guidance to infertile male patients who need assisted reproductive technology.

Pulmonary arterial hypertension (PAH) poses significant clinical management challenges due to gaps in understanding its global epidemiology. We analyzed PAH-related disability-adjusted life years (DALYs), deaths, and prevalence from 1990 to 2021. Age-period-cohort models and regression analyses assessed temporal trends and projected burdens to 2050. Globally, PAH-related DALYs declined by 6.6%, but increased by 13.9% in high socio-demographic index (SDI) countries. Middle SDI regions reported the highest DALYs in 1990 and 2021. Deaths rose by 48.5% worldwide, with high SDI nations experiencing a 76.6% surge. Age-standardized rates (ASRs) of DALYs and deaths decreased across SDI countries, with high-middle SDI regions showing the steepest declines. Younger age groups, especially males, had a higher proportion of global DALYs in earlier years, but the burden shifted toward older populations over time, with this trend more pronounced in high-SDI countries. Age-period-cohort analysis revealed declining DALYs in younger ages but rising rates in older cohorts. By 2050, deaths and prevalence are projected to rise, disproportionately affecting females. Significant regional disparities in PAH burden persist, necessitating targeted policies, improved healthcare access, and early detection strategies, especially in underserved areas. Addressing these disparities is critical for mitigating PAH’ s global impact.

Acute kidney injury (AKI) is a prevalent and serious clinical disease with a high incidence rate and significant health burden. The limited understanding of the complex pathological mechanisms has hindered the development of efficacious therapeutics. Tripartite motif containing 65 (TRIM65) has recently been identified as a key regulator of acute inflammation. However, its role in AKI remains unclear. The present study observed that TRIM65 expression was upregulated in AKI. Moreover, the knockout of the Trim65 gene in mice exhibited a substantial protective impact against rhabdomyolysis, ischemia-reperfusion (I/R), and cisplatin-induced AKI. Mechanistically, TRIM65 directly binds and mediates K48/K63-linked polyubiquitination modifications of voltage-dependent anion channel 1 (VDAC1) at its K161 and K200 amino acid sites. TRIM65 plays a role in maintaining the stability of VDAC1 and preventing its degradation by the autophagy pathway. TRIM65 deficiency attenuates mitochondrial dysfunction in renal tubular epithelial cells during AKI. Conversely, the overexpression of VDAC1 in renal tissues has been demonstrated to negate the protective effect of TRIM65 deficiency on AKI. These findings suggest that TRIM65 may play a role regulating of AKI through the targeting of VDAC1-dependent mitochondrial function, offering potential avenues for the development of new drug targets and strategies for the treatment of AKI.

Glioma subtyping is crucial for treatment decisions, but traditional approaches often fail to capture tumor heterogeneity. This study proposes a novel framework integrating multiplex immunohistochemistry (mIHC) and machine learning for glioma subtyping and prognosis prediction. 185 patient samples from the Huashan hospital cohort were stained using a multi-label mIHC panel and analyzed with an AI-based auto-scanning system to calculate cell ratios and determine the proportion of positive tumor cells for various markers. Patients were divided into two cohorts (training: N = 111, testing: N = 74), and a machine learning model was then developed and validated for subtype classification and prognosis prediction. The framework identified two distinct glioma subtypes with significant differences in prognosis, clinical characteristics, and molecular profiles. The high-risk subtype, associated with older age, poorer outcomes, astrocytoma/glioblastoma, higher tumor grades, elevated mesenchymal scores, and an inhibitory immune microenvironment, exhibited IDH wild-type, 1p19q non-codeletion, and MGMT promoter unmethylation, suggesting chemotherapy resistance. Conversely, the low-risk subtype, characterized by younger age, better prognosis, astrocytoma/oligodendroglioma, lower tumor grades, and favorable molecular profiles (IDH mutation, 1p19q codeletion, MGMT promoter methylation), indicated chemotherapy sensitivity. The mIHC-based framework enables rapid glioma classification, facilitating tailored treatment strategies and accurate prognosis prediction, potentially improving patient management and outcomes.

Tissue repair represents a highly intricate and ordered dynamic process, critically reliant on the orchestration of immune cells. Among these, neutrophils, the most abundant leukocytes in the body, emerge as the initial immune responders at injury sites. Traditionally recognized for their antimicrobial functions in innate immunity, neutrophils now garner attention for their indispensable roles in tissue repair. This review delves into their novel functions during the early stages of tissue injury. We elucidate the mechanisms underlying neutrophil recruitment and activation following tissue damage and explore their contributions to vascular network formation. Furthermore, we investigate the pivotal role of neutrophils during the initial phase of repair across different tissue types. Of particular interest is the investigation into how the fate of neutrophils influences overall tissue healing outcomes. By shedding light on these emerging aspects of neutrophil function in tissue repair, this review aims to pave the way for novel strategies and approaches in future organ defect repair, regeneration studies, and advancements in tissue engineering. The insights provided here have the potential to significantly impact the field of tissue repair and regeneration.