Tumour-associated endothelial cells (TECs) are heterogeneous and plastic regulators of the tumour microenvironment. Their angiogenic, metabolic, barrier, and immunoregulatory programs influence tumour perfusion, metastatic dissemination, immune-cell access, and therapeutic response. However, the causal roles and clinical utility of many newly identified endothelial states remain uncertain.

This review examines the origins and functional heterogeneity of TECs, drawing on findings from single-cell and spatial studies. It discusses the implications of endothelial states for anti-angiogenic therapy, vascular normalization, immune modulation, drug delivery, combination treatment, and therapeutic resistance.

Current evidence reveals endothelial states with distinct functional and therapeutic properties, although most remain descriptively characterized and lack causal or clinical validation. We propose a translational framework integrating single-cell and spatial profiling with protein-level validation, functional perturbation, vascular imaging, and longitudinal biomarkers to distinguish endothelial states that warrant suppression, normalization, reprogramming, or selective targeting.

TEC heterogeneity provides a rationale for precision vascular targeting. Establishing the causal functions and therapeutic relevance of endothelial states will be essential to advance vascular therapy beyond empirical angiogenesis inhibition and guide more selective treatment strategies.

Autoimmune diseases (AIDs) refer to a pathological condition in which the body’s immune tolerance mechanism is disrupted or fails to function properly, leading to damage or dysfunction of its own tissues. Most AIDs are chronic and recurrent, severely affecting patients’ quality of life and ability to work. Currently, there is no curative treatment for AIDs; conventional strategies mainly focus on suppressing immune responses and managing symptoms. However, long-term use of these approaches often leads to significant adverse reactions, and some patients respond poorly to therapy. Therefore, new, safe, and effective treatments are urgently needed. Cell therapy, which involves collecting cells via conventional or bioengineering methods, expanding or modifying them in vitro under specific conditions, and then reinfusing them into the body, has emerged as a promising treatment approach.

This review summarizes current cell-based therapeutic strategies, their clinical applications, and the key challenges in the context of AIDs.

Recent studies have reported remarkable outcomes with cell therapy across various diseases, making it a major research focus. Notably, cell therapy offers distinct advantages for treating AIDs, including targeted immune regulation and the potential for durable remission. Nevertheless, it also faces challenges such as complex manufacturing processes, high costs, safety concerns, and variable efficacy.

Cell therapy is a promising treatment approach for AIDs. However, further research is needed to overcome its current limitations and establish its safety and efficacy in clinical practice.

Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung injury caused by various factors, including infection, trauma and shock. The predominant pathological alteration in its late stages is pulmonary fibrosis (PF), characterised by progressive extracellular matrix deposition, architectural destruction and functional impairment. Particularly in COVID-19-induced ARDS, PF incidence has markedly increased, making it a major sequela impacting patients’ long-term quality of life.

This review systematically examines post-acute lung injury (ALI)/ARDS PF through three perspectives: pathogenesis, prediction and treatment.

Mechanistically, the fibrotic process involves epithelial injury and mesenchymal transition, fibroblast activation with aberrant extracellular matrix remodelling, dysregulated inflammation with immune cell involvement and clinical management-related factors. For prediction, various biomarkers (including growth factors, matrix proteins and inflammatory markers) and imaging features (particularly high-resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) characteristics) demonstrate clinical value. Integrated multiparameter models incorporating artificial intelligence show promise for early identification and risk stratification of high-risk patients. Therapeutic strategies encompass anti-inflammatory approaches (e.g., corticosteroids and antioxidants), antifibrotic agents (pirfenidone and nintedanib), cell-based therapies (mesenchymal stem cells and exosomes) and emerging genetic/RNA interventions. However, specific preventive and therapeutic approaches tailored to the post-ALI/ARDS PF population remain inadequate in clinical practice.

Future research should focus on elucidating underlying mechanisms, refining early-warning systems, exploring personalised treatments and facilitating clinical translation. The ultimate goal is to transition from traditional supportive care to proactive prevention through enhanced clinical surveillance, early prediction and rational intervention, thereby preventing fibrosis progression and improving outcomes in ARDS survivors.

Prader-Willi syndrome (PWS) is a leading genetic cause of life-threatening obesity, presenting with hypotonia and feeding difficulties in infancy, progressing to hyperphagia, cognitive impairment and behavioural challenges from childhood. It is a rare imprinting disorder caused by gene silencing at the 15q11–q13 locus. Early detection through newborn bloodspot screening (NBS) could enable timely interventions such as growth hormone therapy, dietary management and behavioural support to improve health and developmental outcomes for the affected infants.

This review applies the Australian Newborn Bloodspot Screening National Policy Framework as a reference to evaluate the suitability of incorporating PWS into NBS programs. The review outlines benefits and challenges in relation to key criteria used by this Framework, including condition severity, early detection benefits and screening test reliability.

Emerging screening technologies are recognised for their high sensitivity and specificity and could be integrated into existing NBS workflows using dried blood spots. However, several challenges outlined in this review need to be addressed, including the lack of cost-effectiveness data for population-wide PWS screening programs and the absence of a curative treatment for PWS.

Expanding NBS to include PWS has the potential to improve health and developmental outcomes through earlier diagnosis and timely interventions. Successful implementation will depend on addressing the remaining challenges.

Necrotizing enterocolitis (NEC) is a leading gastrointestinal emergency in preterm infants, characterized by severe epithelial injury, dysregulated inflammation, and defective mucosal repair. Intestinal stem cells (ISCs) at the crypt base are essential for epithelial renewal and barrier restoration after injury.

We summarized recent advances in the molecular and cellular mechanisms governing ISC injury and regeneration in NEC, emphasizing canonical repair pathways, niche-derived regulatory circuits, and emerging ISC-targeted therapies.

NEC disrupts ISC survival, proliferation, and differentiation through aberrant innate immune activation, microbial dysbiosis, and impairment of Wnt, Notch, and epidermal growth factor (EGF) signalling. ISC function is also shaped by interactions with Paneth cells, mesenchymal niche components, immune cells, and microbial metabolites. Disruption of this niche compromises crypt regeneration, perpetuates barrier dysfunction, and amplifies intestinal inflammation. Restoring ISC activity and niche integrity has therefore prompted interest in growth factor supplementation, microbiota modulation, immune-based interventions, and stem cell-oriented approaches.

ISC-centred regenerative failure provides an integrated framework linking epithelial biology, immunology, and microbiome research in NEC. Restoring ISC function and niche integrity represents a promising therapeutic direction with experimental and translational relevance.

Fibrosis is characterised by the pathological accumulation of extracellular matrix components and represents both a driver and consequence of chronic tissue injury across multiple organs and is a major contributor to global morbidity and mortality. Despite this substantial clinical burden, approved antifibrotic therapies remain limited. Adiponectin, an adipokine secreted predominantly by adipocytes, is an endogenous antifibrotic mediator with potential therapeutic applications.

This review examines the pathobiology of fibrosis, the molecular mechanisms underlying adiponectin-mediated antifibrotic effects, and current advances in adiponectin-based therapeutic development. Evidence from preclinical studies across multiple organ system is discussed, with a focus on adiponectin signaling pathways and receptor agonists.

Adiponectin actsprimarily through its cognate receptors AdipoR1 and AdipoR2, adiponectin suppresses key profibrotic signalling cascades, including TGF-β/Smad, NF-κB, Wnt/β-catenin, Notch and platelet-derived growth factor pathways, while simultaneously promoting anti-inflammatory, antioxidant and cytoprotective responses. Preclinical studies demonstrate that adiponectin deficiency exacerbates fibrotic remodelling in the liver, lungs, heart, kidneys, skeletal muscle and skin, whereas genetic or pharmacological augmentation of adiponectin signalling attenuates fibrosis progression. Two adiponectin receptor agonists, the small molecule AdipoRON and the peptide mimetic ALY688, have shown promising antifibrotic efficacy across multiple disease models.

Adiponectin signaling represents a promising therapeutic strategy for the prevention and treatment across multiple organs. Further investigation is needed to address current challenges and establish the safety, efficacy, and translational potential of adiponectin-based therapies in clinical settings.

Immune-related diseases contribute substantially to global morbidity and mortality. CD8+ T cells play a critical role in adaptive immunity by eliminating virus-infected and malignant cells. The biology of CD8+ T cells is governed by tightly regulated gene expression programs, and disruption of these programs can lead to diverse immunopathologies and malignancies. This article evaluates our current understanding of post-transcriptional and translational regulation of gene expression in CD8+ T cells by RNA-binding proteins.

Relevant and up-to-date literature was critically analysed to gain mechanistic insights into the roles of RNA-binding proteins in CD8+ T cell biology and to identify key knowledge gaps and future directions, with particular emphasis on therapeutic implications.

RNA-binding proteins regulate diverse aspects of CD8+ T cell biology, including differentiation, cytokine production, stress adaptation and proliferation. Recent studies further reveal how dysregulated expression and function of RNA-binding proteins contribute to hyperinflammation and haematological malignancies.

RNA-binding proteins are emerging as key post-transcriptional and translational checkpoint regulators of CD8+ T cell biology and represent promising therapeutic targets for immune-related diseases; however, substantial mechanistic and disease-specific studies, as well as rigorous translational validation, are required before RNA-binding protein-targeted therapeutic strategies can be safely and effectively advanced into clinical practice.

Multi-omics research is reshaping precision nephrology by linking genetic susceptibility, epigenetic regulation, transcriptional state, protein abundance, metabolic activity and spatial tissue context within integrated analytical frameworks.

We critically reviewed recent technological advances and applications of multi-omics in kidney diseases, with particular attention to biomarker discovery and clinical translation, and discussed the challenges and future directions of multi-omics integration and its application in precision medicine.

Emerging approaches, including single-cell and spatial omics, artificial intelligence-assisted analytics and integrative computational frameworks, have substantially improved the resolution of renal pathophysiology and molecular heterogeneity. These advancements not only reveal novel molecular pathways underlying chronic kidney disease, diabetic kidney disease, acute kidney injury and immune-mediated nephropathies, but also significantly facilitate biomarker discovery and therapeutic target prioritization. However, major challenges remain, including limited cohort diversity, high analytical complexity, lack of standardized pipelines, insufficient external validation and barriers to clinical implementation, such as cost, scalability and regulatory integration.

Collectively, multi-omics strategies are reshaping kidney disease research and hold considerable promise for advancing precision diagnosis, risk stratification and personalized therapeutics. Future efforts should prioritize harmonized multicentre datasets, longitudinal validation, explainable artificial intelligence models and clinically actionable frameworks to bridge the gap between omics discovery and routine nephrology practice.

Spinal Muscular Atrophy (SMA) is caused by a deficiency of the survival motor neuron (SMN) protein due to loss of SMN1 and inefficient compensation by SMN2. This genetic architecture has driven the development of precision therapeutics. Over the past decade, SMA management has progressed from supportive care to RNA-based splicing modulation and gene replacement therapy.

This review analyzes the evolution of three therapeutic waves in SMA management: antisense oligonucleotides (nusinersen) for SMN2 splicing correction; systemic small-molecule splicing modifiers (risdiplam) addressing SMA as a multisystem disorder; and gene replacement therapy (onasemnogene abeparvovec), including recent intrathecal formulations expanding patient eligibility.

Precision therapies have profoundly altered the disease trajectory, especially when administered presymptomatically. Nusinersen sustains splicing correction, risdiplam restores SMN across central and peripheral tissues, and gene replacement offers durable, one-time genetic correction. However, critical challenges persist regarding therapeutic durability, optimal treatment sequencing, systemic involvement, and long-term safety.

The evolution of SMA therapies has transformed neurogenetics. Clinical benchmarks have successfully shifted from reactive, symptomatic management to proactive, molecularly targeted precision medicine.

Myocardial infarction (MI) remains a critical focus in cardiovascular research, with in vitro models serving as essential tools for investigating pathophysiological mechanisms and evaluating therapeutic strategies. Despite their widespread use, the clinical relevance of these models is often assumed rather than rigorously validated.

In this review, we systematically examined 28 studies from the last decade that employed in vitro co-culture models of MI, selected via a PubMed search according to pre-defined criteria. Each study was analysed with respect to ischaemia/reperfusion (I/R)-mimicking conditions applied, species and cell types used, and strategies for verifying clinical relevance.

Our analysis revealed considerable heterogeneity in experimental design. Protocols for inducing I/R stress and the duration of treatment varied widely between studies, underscoring a lack of methodological standardization. Cell sources included swine, rat, mouse and human-derived cells, with nearly half of the studies utilizing cross-species combinations – often without addressing the implications for translational validity. Verification strategies were inconsistently applied and frequently limited to basic endpoints such as cell viability and oxidative stress assays. Some studies also employed in vivo models to validate in vitro findings.

To enhance translational potential, future studies should prioritize human-derived cells, standardized I/R protocols and verification strategies that better recapitulate MI pathology.

The sphingolipid rheostat – the interconversion between pro-apoptotic ceramide (Cer) and pro-survival sphingosine-1-phosphate (S1P) – governs female reproductive homeostasis. This review integrates mechanistic evidence across the reproductive continuum to elucidate how compartmentalised disruptions of this axis drive divergent pathologies.

A systematic search up to 2026 across PubMed and Web of Science identified molecular mechanisms and translational models linking sphingolipid signalling to ovarian ageing, polycystic ovary syndrome (PCOS), endometriosis, adenomyosis and uterine fibroids.

Pathological Cer accumulation drives mitochondrial outer membrane permeabilisation (MOMP) and cytochrome c release, accelerating follicular atresia in primary ovarian insufficiency (POI). Conversely, PCOS is associated with heterogeneous remodeling of follicular-fluid sphingolipids, compromising oocyte competence. Within uterine and peritoneal microenvironments, a hyper-activated S1P axis operating via S1PR1–3 networks acts as a core pathogenic engine. This axis exhibits a threshold-dependent dual nature: low thresholds promote homeostatic survival, whereas high thresholds drive M2 macrophage polarisation for immune evasion and cross-link with TGF-β/Smad and Activin A cascades to stimulate fibroblast-to-myofibroblast transdifferentiation (FMT) and extracellular matrix deposition in endometriosis and fibroids. Additionally, the SphK/S1P axis amplifies chronic pelvic pain by modulating nerve growth factor (NGF) and transient receptor potential vanilloid 4 channels.

The sphingolipid axis constitutes a unifying molecular rheostat in reproductive medicine. Mapping these compartmentalised lipidomic signatures enables high-resolution diagnostics, while targeted sub-receptor antagonists and non-hormonal drug repurposing offer promising, fertility-preserving therapeutic frontiers. However, successfully translating these lipid-targeted interventions into clinical practice demands addressing key bottlenecks regarding systemic off-target toxicities and engineering advanced, tissue-specific delivery platforms.

Spontaneous intracerebral hemorrhage (sICH) remains associated with high mortality and long-term disability worldwide. Since the publication of the Surgical Trial in Intracerebral Haemorrhage (STICH) in 2005, numerous randomized controlled trials have evaluated surgical, pharmacological, and physiological interventions, yet most have not demonstrated consistent improvements in functional outcomes.

We critically reviewed major randomized controlled trials and influential studies of acute sICH treatment published over the past two decades, with particular attention to surgical strategies, physiological and pharmacological interventions, treatment timing, patient selection, and sex-related biological heterogeneity.

Most conventional surgical and single-target medical interventions yielded neutral or modest results. Recent trials suggest that carefully selected surgery, early intervention, and bundled protocolized care may provide greater benefit. However, optimal treatment timing and sex-specific biological differences remain insufficiently investigated.

Further progress in acute sICH treatment will require time-sensitive, mechanism-informed, anatomically tailored, and sex-aware multimodal treatment strategies rather than isolated interventions.

Accumulating evidence suggests that long COVID (LC) is mediated by chronic immune activation, oxidative stress and metabolic dysregulation. These processes may impair glucose homeostasis and promote insulin resistance (IR). However, no prior meta-analysis has systematically and quantitatively evaluated IR indices and related biomarkers in LC compared with normal controls.

To systematically review and meta-analyse IR indices including HOMA-IR, HOMA-%B, HOMA-%S, insulin, fasting and random blood sugar (FBG, RBS), glycated haemoglobin (HbA1c), C-peptide and adipokine levels in individuals with LC compared with normal controls.

PubMed, SCOPUS, SciFinder and Google Scholar databases were searched for relevant studies from inception to September 2025. Fifty-six eligible studies were included, comprising 9623 participants, 5340 LC patients and 4283 normal controls.

LC disease is characterized by elevated HOMA-IR (standardized mean difference, SMD = 0.539; 95% confidence interval, CI: 0.311; 0.766), insulin (SMD = 0.424; 95% CI: 0.113; 0.735), FBG and RBS (SMD = 0.734; 95% CI: 0.190; 1.277, SMD = 0.325; 95% CI: 0.133; 0.517). Furthermore, reduced HOMA-%S was observed in LC patients versus normal controls. Publication bias was generally low, though evidence of small-study effects was observed for several outcomes. The Immunological Confounder Scale was employed to evaluate study quality, revealing an overall intermediate methodological quality.

Our results show that LC is associated with multiple abnormalities in glucose homeostasis, including increased HOMA-IR, hyperglycaemia and impaired insulin sensitivity indices, sustained metabolic disturbances beyond the acute phase.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with limited treatment options and a poor prognosis. Lung cancer (LC) is one of the most common comorbidities in IPF, and IPF is recognized as an independent risk factor for the development of LC. In recent years, increasing evidence has suggested that these two diseases may share convergent genetic, epigenetic and cellular mechanisms, particularly within their microenvironments.

A comprehensive literature search was performed across PubMed, Web of Science, and Google Scholar databases to identify relevant studies focusing on the shared cellular components, immune and stromal behaviors, and pathogenic pathways within the microenvironments of IPF and LC.

This review delineates the convergent features of the IPF and LC microenvironments by synthesizing the functional reprogramming of key cellular constituents. The immunological landscape is characterized by aberrant macrophage polarization, T-cell exhaustion and the accumulation of immunosuppressive myeloid-derived suppressor cells and immature dendritic cells. Furthermore, profound stromal alterations are observed, encompassing fibroblast activation, pathological extracellular matrix remodelling, epithelial–mesenchymal transition and dysregulated angiogenesis. These common cellular and molecular alterations may simultaneously drive fibrosis progression and tumorigenesis.

A deeper understanding of the relationship between the IPF and LC microenvironments will help identify shared pathological mechanisms and provide new insights for developing more targeted diagnostic and therapeutic strategies for idiopathic pulmonary fibrosis associated with lung cancer (IPF-LC).