Bronchopulmonary dysplasia (BPD) is a common and serious complication among preterm infants, particularly those born at extremely low gestational ages. It is primarily characterized by impaired alveolar and vascular development. Inflammation is increasingly recognized as a central mechanism in its pathogenesis. Both prenatal factors, such as intrauterine infection, and postnatal insults, including mechanical ventilation, oxygen toxicity, and infection, can trigger and sustain a dysregulated inflammatory response in the immature lung. This response involves the activation of inflammatory cells, such as neutrophils and macrophages, and the release of pro-inflammatory mediators, reactive oxygen species (ROS), and proteases. These factors disrupt critical developmental signaling pathways and contribute to alveolar simplification and abnormal vascular growth, which are the hallmark features of BPD. Current therapeutic strategies aim to limit these inflammatory processes and support lung development. Established interventions like caffeine and corticosteroids have demonstrated varying levels of effectiveness and safety. Emerging therapies-including anti-cytokine agents, inflammasome inhibitors, and stem cell-based approaches-offer promising avenues by specifically targeting the inflammatory cascade. Additionally, supportive strategies such as non-invasive ventilation, careful oxygen titration, and optimal nutrition play essential roles in reducing initial injury and facilitating recovery. Inflammation is a key mediator linking diverse perinatal insults to the disrupted lung development seen in BPD. A deeper understanding of the inflammatory mechanisms and timely, targeted interventions may offer improved outcomes for this vulnerable population.

Osteoarthritis (OA) is the most prevalent chronic degenerative joint disorder worldwide, characterized by progressive cartilage degradation, subchondral bone remodeling, synovial inflammation, and impaired mobility. Growing evidence has established mitochondrial dysfunction-including impaired oxidative phosphorylation (OXPHOS), excessive reactive oxygen species (ROS) generation, disrupted mitochondrial dynamics, and dysregulated mitophagy-as an early and pivotal driver of OA pathogenesis. These bioenergetic failures not only disrupt chondrocyte metabolism but also amplify inflammation, matrix degradation, and cell death. In recent years, mitochondrial transplantation has emerged as a revolutionary therapeutic paradigm, aiming to restore cellular homeostasis by delivering functional mitochondria into damaged chondrocytes. This review systematically summarizes the molecular mechanisms of mitochondrial dysfunction in OA and highlights three major therapeutic strategies: (1) cell-based approaches, particularly mesenchymal stem cell (MSC)-mediated mitochondrial transfer via tunneling nanotubes (TNTs) or extracellular vesicles (EVs); (2) cell-free approaches, utilizing purified mitochondria or MitoEVs for direct transplantation; and (3) engineered mitochondrial transplantation, integrating bioengineering, nanotechnology, and genetic modification to enhance mitochondrial quality, delivery efficiency, and therapeutic persistence. We further discuss opportunities and challenges in clinical translation, including standardization of mitochondrial preparation, optimization of delivery systems, immunological safety, and regulatory classification. Collectively, mitochondrial transplantation represents a disruptive strategy that directly addresses the bioenergetic collapse of chondrocytes and offers a promising avenue for disease-modifying therapy in OA. Future advances in mechanistic elucidation, technological optimization, and multicenter clinical trials will be crucial to transform "mitochondrial medicine" from experimental concept to clinical reality.

The management of bronchial asthma has evolved from a one-size-fits-all approach to the era of precision medicine, which is guided by intrinsic phenotypes. This article systematically reviews the mechanisms of action of current targeted biologics (targeting pathways such as IgE, IL-5/IL-5R, IL-4/IL-13, and TSLP), the efficacy and safety data derived from pivotal clinical trials, and the biomarker systems that guide clinical decision-making, further elaborating on how to implement tailored individualized therapy based on patient-specific characteristics. However, existing biologics still face challenges including the need for long-term administration and the inability to reverse disease progression. Therefore, this article focuses on the transformative prospects of next-generation therapeutic modalities. Cell therapy represents the most promising breakthrough, with its core shifting from "passive suppression" to "active regulation and remodeling". This is mainly reflected in three cutting-edge areas: cellular reprogramming (e.g., converting pathogenic Th2 cells into homing-competent regulatory T cells), engineering modification (e.g., designing CAR-NK cells with dual functions of targeted clearance and immune regulation), and multifunctional immune/repair modulation (e.g., utilizing mesenchymal stem cells and their exosomes to suppress immune abnormalities at the source and promote tissue repair). Collectively, these strategies drive a fundamental shift in treatment goals from symptom control to the induction of long-term immune tolerance and even functional cure. In conclusion, the future management of asthma will be a dynamically evolving individualized integrated system. By deeply integrating targeted biologics, intelligent advanced cell therapies, and continuously optimized precision management strategies, we are expected to ultimately establish a multi-level, closed-loop diagnosis and treatment pathway for each patient, laying the foundation for achieving long-term high-quality remission.

Epithelial stem cells in the interfollicular epidermis (IFE) and hair follicle (HF) play key roles in maintaining and regenerating the skin barrier by balancing self-renewal and differentiation. These fate decisions are governed by transcriptional and epigenetic mechanisms that respond to context-dependent signals from the skin microenvironment. In the IFE, basal stem cell divisions follow a stable pattern but rely on tightly regulated transcription factors and chromatin states to ensure proper epidermal maintenance. In contrast, HF stem cells exhibit a higher degree of plasticity that allows for rapid adaptation to changing environments, including IFE regeneration following injury. While this plasticity is critical for epidermal integrity, it can also drive disease onset if transcriptional programs become disrupted. This review provides a comprehensive analysis of how transcriptional and epigenetic regulators guide stem cell fate decisions required in the IFE and HF that promote epidermal homeostasis. We also explore how these programs are altered in various pathological contexts in the skin. By comparing differentiation mechanisms in the IFE and HF compartments, we highlight how dynamic control of gene expression sustains skin homeostasis.

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by increased platelet destruction and impaired megakaryopoiesis within a dysregulated bone marrow niche. Conventional therapies often achieve only transient platelet recovery, failing to restore immune tolerance, thereby underscoring the need for mechanism-based therapeutic strategies. Mesenchymal stem cells (MSCs) have emerged as promising candidates due to their ability to modulate immune responses and repair the hematopoietic microenvironment. This review synthesizes current evidence regarding the biological properties, immunomodulatory mechanisms, and therapeutic applications of MSCs in ITP, emphasizing intrinsic abnormalities of patient-derived MSCs and the corrective potential of exogenous MSCs from distinct tissue sources. It further integrates emerging insights into MSC functional heterogeneity, optimization of culture conditions, priming strategies, and cellular engineering approaches that may enhance therapeutic efficacy and safety. By highlighting the interplay between immune tolerance restoration and bone marrow niche remodeling, this review provides a translational framework that links mechanistic understanding to the future clinical development of MSC-based therapies for ITP.

Effective pharmacological therapies for small abdominal aortic aneurysms (AAAs) remain lacking. Most preclinical work focuses on aneurysm initiation rather than treatment of established disease, reducing translational relevance.

The lymphatic vasculature maintains tissue fluid homeostasis, lipid transport, and immune surveillance. Beyond these classical roles, lymphatic vessels regulate tissue development and repair through lymphangiocrine signalling, whereby lymphatic endothelial cells (LECs) secrete mediators such as Reelin, R-spondin-3, and CCL21 that modulate stem cell niches, immune trafficking, and regeneration. Ageing-associated lymphatic dysfunction, driven by LEC senescence, impaired lymphangiogenesis, and lymph node stromal remodelling, leads to defective tissue repair, chronic low-grade inflammation, and increased susceptibility to diseases including cancer, cardiovascular disease, and neurodegeneration.

Cranial sutures are dynamic growth sites that balance bone growth with mesenchymal patency to accommodate cranial expansion during development. While intramembranous ossification has traditionally been considered the default mechanism of suture fusion, accumulating evidence demonstrates that endochondral pathways might also play a significant role under both physiological and pathological conditions. In this review, we contrast normal developmental ossification processes with premature fusion in craniosynostosis, integrating histological, molecular, and imaging data. We highlight the context-dependent nature of cranial suture biology, influenced by embryonic origin, local signalling gradients, and genetic perturbations. Recognizing divergent ossification mechanisms reframes our understanding of both normal and premature suture fusion and has clinical implications for mechanism-specific therapeutic strategies. Finally, we outline areas for future investigation, including high-resolution profiling of human sutures across developmental stages, to establish a normative framework for cranial suture biology and inform mechanism-driven regenerative approaches.

The worldwide diabetes epidemic underscores the urgent need for innovative therapeutic approaches. This review provides an in-depth analysis of the significant potential of marine polysaccharides in both the prevention and management of diabetes. Derived from algae, animals, and microorganisms, these polymers offer distinct structural advantages compared to their terrestrial counterparts, such as increased sulfate content and a wider range of molecular weights. We systematically elucidate their multi-targeted hypoglycemic mechanisms, which include the inhibition of digestive enzymes (α-amylase and α-glucosidase), enhancement of insulin sensitivity, promotion of peripheral glucose metabolism, protection of pancreatic β-cell function, and modulation of gut microbiota. A comprehensive analysis of the intricate structure-activity relationships highlights the influence of specific structural characteristics on bioactivity. Additionally, the utilization of marine polysaccharides in novel drug delivery systems and strategies to enhance efficacy is examined. Despite challenges related to standardization and the necessity for more detailed mechanistic understanding, marine polysaccharides, due to their diverse actions, biocompatibility, and sustainability, present as a promising avenue for the development of next-generation, multi-targeted therapies and functional foods. This approach ultimately offers a holistic strategy for diabetes management, leveraging the extensive resources available within the marine environment.

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is an established marker of normal and cancer stemlike cells. LGR5 has been implicated in promoting cancer cell plasticity that drives tumorigenesis, metastasis, and therapeutic resistance. LGR5 rapidly and constitutively internalizes and potentiates Wnt (Wingless/Int-1)/β-catenin and adhesion signaling pathways, though its precise mechanisms and interacting partners remain unresolved. An improved understanding of LGR5 signaling may provide invaluable insight into its intricate and important functions in cancer progression. Moreover, several LGR5-targeting therapies, including peptibody- and antibody-drug conjugates and bispecific antibodies, are showing promising efficacy and tolerability in colorectal cancer and other tumor types. This review discusses the cancer-related functions of LGR5 and explores the preclinical and clinical approaches to therapeutically target this enigmatic protein.

Both the levels and duration of gene expression play critical roles in many biological processes. Recent studies have further revealed that the dynamics of oscillatory versus sustained gene expression also provide essential regulatory information during cell proliferation and differentiation. Oscillatory expression, governed by intracellular negative feedback loops and intercellular coupling with appropriate delays, promotes the proliferation of stem cells, whereas sustained expression typically drives cells toward quiescence or differentiation. Over time, oscillations can result in the gradual upregulation or downregulation of downstream factors or shifts in phase relationships between distinct oscillators, thereby functioning as a timer for cell state transition. Moreover, oscillation frequency encodes critical cues for cell fate choice. Thus, oscillatory dynamics add an extra dimension to the informational landscape of gene expression. Here, we discuss recent advances in our understanding of how oscillatory gene expression is regulated and how it influences the proliferation and differentiation of stem cells.

Nucleic acid-based therapeutics, which involve the manipulation of genetic materials to treat or prevent diseases, have gained considerable attention, leading to the approval of medicines such as COVID-19 vaccines, patisiran (Onpattro), and nusinersen (Spinraza). However, their clinical application is hindered by challenges such as nuclease degradation, poor biodistribution, limited cellular uptake, and inefficient endosomal escape. Extracellular vesicles (EVs), which are natural nanoscale drug delivery systems derived from various eukaryotic and prokaryotic cells, offer a safe, efficient, specifically targeted, and non-pathogenic method for nucleic acid delivery. In this review, we summarize the classical methods and the latest research advances in EV preparation and nucleic acid loading. Additionally, we review the primary administration routes for nucleic acid-loaded EVs, such as intravenous, local, oral, intranasal, and inhalation delivery. By addressing these aspects, this review aims to guide the optimal design and clinical application of nucleic acid-loaded EVs.

ARG1 catalyzes the conversion of L-arginine to L-ornithine, urea, polyamines, and L-proline, thereby balancing nitrogen detoxification with tissue-specific roles in proliferation and immunity. This review delineates the context-dependent functions of ARG1 across diverse cell types-including tumor cells, immune cells, endothelial cells, keratinocytes, and stem cells. In tumors, ARG1 drives immunosuppression and metabolic reprogramming but can paradoxically suppress tumorigenesis. Immune modulation via ARG1-polyamine crosstalk regulates T cell differentiation, macrophage polarization, and microbiota interactions, influencing infection and autoimmunity. Endothelial ARG1 exacerbates obesity-related vascular dysfunction, while keratinocyte ARG1 impacts wound healing and psoriasis. Emerging therapies-such as ARG1 inhibitors, engineered extracellular vesicles, and microbiome interventions-show preclinical promise in cancer, cardiovascular, and neurodegenerative diseases. By mapping ARG1's spatiotemporal metabolic networks, this work highlights its dual roles and positions ARG1 as a central player for precision medicine in complex pathologies.

Zone II flexor tendon injuries remain among the most challenging conditions in hand surgery due to the region's complex anatomy and high rates of postoperative complications, particularly adhesion formation and the resulting loss of range of motion. Although platelet-rich plasma (PRP), mesenchymal stromal cell (MSC) therapies, and hyaluronic acid (HA) have demonstrated therapeutic potential in other musculoskeletal conditions, their effectiveness in preventing postoperative adhesions following zone II flexor tendon repair, specifically, remains unclear. A comprehensive review of the literature was conducted using PubMed and Google Scholar to identify randomized controlled trials, prospective and retrospective cohort studies, and original research evaluating the use of PRP, MSCs, or HA in zone II flexor tendon repair. Only full-length English-language studies specifically addressing zone II injuries were included. Studies were excluded if they did not focus explicitly on zone II flexor tendon injuries, lacked clearly reported outcomes, or failed to assess postoperative adhesion formation and functional recovery. Search terms included but were not limited to "Zone II flexor tendon," "PRP Zone II flexor tendon repair," "stem cell Zone II flexor tendon repair," "hyaluronic acid Zone II flexor tendon repair." Data from both human and animal studies were collected to compare postoperative adhesion formation and functional outcomes. Studies across all compounds showed inconsistent results in animal and human trials. PRP for zone II flexor tendon repair showed limited and inconsistent benefits, with most preclinical and clinical trials reporting no significant improvement in adhesion prevention or range of motion. Higher leukocyte concentrations in PRP were associated with increased inflammatory activity, potentially promoting scar formation. In contrast, mesenchymal stromal cell therapies, particularly adipose- and synovium-derived MSCs, demonstrated promising preclinical effects by modulating inflammation, reducing scar-related gene expression, limiting apoptosis, and enhancing tendon gliding though statistical significance was not always achieved. HA showed the most promising results with a majority of animal and human studies consistently reducing adhesion formation and improving tendon excursion and functional outcomes in the long-term. Across all the examined studies, no agent- PRP, MSCs, or HA- consistently prevented postoperative adhesions or reliably improved range of motion following zone II flexor tendon repair, specifically. The complex anatomy of zone II, inconsistent functional outcomes, limited mechanistic understanding, and wide methodological variation among studies, continue to limit the ability to draw definitive conclusions. Cost and accessibility further complicate the clinical adoption of these adjuncts. Current evidence does not support the routine use of PRP, MSCs, or HA for preventing postoperative adhesions after zone II flexor tendon repair. Nevertheless, while research on this topic remains limited, a few existing studies have shown promising trends that warrant further investigation. Future research should incorporate age-specific analyses, standardized agent formulations, clearer mechanistic evaluation, and optimized delivery methods to better determine whether these adjuncts can consistently and reliably improve outcomes in this anatomically challenging region.

Both primary and metastatic brain tumors rely on signals from the surrounding environment for their survival and progression. In particular, the most common and lethal brain cancer, glioblastoma (GBM), derived from glial cells (astrocytes or microglia), has been shown to integrate into synaptic networks and to receive paracrine signals from neighbouring tumor microenvironment (TME) cells. There is increasing evidence that metastatic disease in the brain exhibits similar behavior. The TME both maintains malignant cells and is maintained by them, a process that relies on cancer stem cells (CSCs). These stem cells and their signaling mechanisms, including in the case of GBM, "GSCs," provide possible novel targets for immunotherapy. In this review, we will discuss the integration of primary and malignant brain tumors into normal synaptic networks, the role of tumor stem cells and the TME in this integration, and the potential for immunotherapeutic targeting of these processes.

This review synthesizes evidence from recent clinical and mechanistic studies published between 2015 and 2024 to provide updated insights into the prevention and management of adverse drug reactions (ADRs) associated with first-line anti-tuberculosis drugs (ATDs)-namely isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol (EMB)-which are essential for tuberculosis (TB) treatment but frequently cause significant ADRs that threaten therapeutic success. We examine four major toxicities: hepatotoxicity (primarily from INH and RIF, mediated by oxidative stress, mitochondrial dysfunction, and cytochrome P450 induction); peripheral neuropathy (driven by INH-induced pyridoxine depletion and EMB-related copper chelation leading to optic and axonal damage); central nervous system (CNS) toxicity (notably INH-induced seizures due to GABAergic disruption); and myelosuppression (mainly RIF- or PZA-related, involving oxidative injury to hematopoietic stem cells and impaired DNA synthesis). Key risk factors include advanced age, malnutrition, pre-existing organ dysfunction, and pharmacogenetic variations (eg, NAT2 acetylator status). Management strategies emphasize protocol-driven monitoring-including baseline and serial liver function tests (LFTs), complete blood counts (CBC), neurologic exams, and monthly visual assessments for EMB-and graded interventions based on severity thresholds (eg, temporary discontinuation if ALT >3× upper limit of normal (ULN) with symptoms or >5× ULN asymptomatic), alongside targeted therapies such as pyridoxine for neuropathy and N-acetylcysteine for hepatotoxicity. Proactive measures, including pretreatment risk stratification, patient education, and multidisciplinary coordination, are critical to optimizing adherence and outcomes. Effective management of first-line anti-TB drug toxicity requires mechanism-informed monitoring, individualized interventions, and proactive patient education to maintain treatment adherence and improve global TB outcomes.

To systematically evaluate the efficacy and safety of mesenchymal stem cell (MSC) therapy for patients with Multiple System Atrophy (MSA) by synthesising available clinical trial evidence and clarifying signals of disease modification.

Protein S-palmitoylation is a highly conserved posttranslational lipid modification that occurs on cysteine residues and critically influences protein maturation, subcellular localization, trafficking, and stability. Owing to its unique reversibility and dynamic nature, S-palmitoylation plays a pivotal role in cancer. This review comprehensively summarized the expression profiles and distribution of key cancer-related S-palmitoylation enzymes in recent years. Importantly, we highlight the specific mechanisms by which the dual states of palmitoylation and depalmitoylation function as a dynamic regulatory axis during the transformation of cancer cells into cancer stem cells and during the transition from a normal tissue environment to a tumor microenvironment. Furthermore, we discussed emerging therapeutic strategies targeting S-palmitoylation, including the development of specific inhibitors and competitive blockade of substrate-binding sites, which offer additional insights into the translational potential of S-palmitoylation as a therapeutic target for cancer.

Male factors contribute to approximately half of all infertility cases globally, with heat stress recognized as a major environmental determinant of impaired male reproductive function. Extensive research indicates that heat stress disrupts spermatogenesis through multiple pathways, including testicular oxidative stress (OS), compromise of the blood-testis barrier, and dysregulation of the spermatogonial stem cell niche. As global temperatures rise, the prevalence of heat-induced reproductive impairment is increasing, underscoring the urgent need to identify safe and effective interventions that target the underlying oxidative damage. L-citrulline demonstrates significant potential in the field of male reproductive protection. However, existing reviews primarily focus on general discussions of antioxidants, lacking a systematic analysis of the specific mechanisms of L-citrulline. This review systematically synthesizes current knowledge on the molecular mechanisms of heat stress-induced oxidative injury in male gametes. Particular emphasis is placed on the multifaceted protective role of L-citrulline, which acts through synergistic mechanisms involving modulation of the arginine-nitric oxide (NO) pathway, preservation of mitochondrial homeostasis, restoration of autophagy flux, and suppression of apoptotic signaling. By integrating experimental and clinical evidence, this analysis aims to elucidate both the translational potential and the key scientific challenges of L-citrulline supplementation in male reproductive health. The review seeks to advance the translation of L-citrulline from basic research to clinical practice and to propose novel nutritional strategies for improving fertility outcomes in men exposed to heat stress.

Male infertility due to spermatogenic failure remains a global challenge. While in vitro spermatogenesis (IVS) offers potential for fertility preservation, recapitulating the complex, species-specific testicular niche remains a formidable task. This review evaluates IVS progress and bottlenecks across rodents, primates, domestic animals, and humans.