The advent of nanoparticle technology has transformed oncology therapeutics through its capacity for accurate drug delivery and regulated pharmaceutical release, boosting treatment effectiveness while minimizing adverse reactions. Various nanostructures, including polymeric carriers, liposomal formulations, and metal-based nanoparticles, can be engineered with tumor-specific targeting molecules to facilitate cellular uptake in malignant cells. Despite these advancements, issues such as production scalability, potential chronic toxicity, and regulatory approval processes still need to be addressed. Viral nanoparticles and virus-like particles (VLPs) represent innovative tools in nanotechnology and biomedicine, offering exceptional potential for targeted therapies, immune modulation, and diagnostic applications. Their natural biocompatibility, precise structural organization, and capacity for surface modification make them highly suitable for developing strategies to treat malignant tumors. Alongside VLP development, other approaches have also been investigated, such as magnetic hyperthermia, where magnetic nanoparticles are used to generate localized heat under an external magnetic field, selectively destroying cancer cells while sparing healthy tissue. This paper presents a brief review of nanocarriers in drug delivery systems and discusses the integration of nanoparticles, viral nanoparticles, and VLPs. Additionally, we explore the challenges and propose cutting-edge solutions, offering a forward-looking perspective on how the combination of these advanced technologies could transform oncology.

Targeted drug delivery remains a major challenge in cancer therapy, often limiting both efficacy and safety. Although microRNA sponges and short-hairpin RNAs show potential for gene-based cancer treatment, their clinical use is restricted by delivery inefficiency, off-target effects, cytotoxicity, and instability. Viral vectors offer high efficiency but are associated with issues such as immune responses, insertional mutagenesis, and limited cargo capacity. Non-viral carriers are safer and more affordable but suffer from poor transfection efficiency, instability, and inadequate endosomal escape. These limitations hinder the clinical application of RNA therapeutics. The Vir-inspired Biotechnical Vector (VIBV) is a novel hybrid platform that combines viral and non-viral elements with nanotechnology to enable personalized, tumor-specific gene therapy. Engineered with a spindle-shaped nanocore and a polyethylene glycolylated liposomal shell, VIBV ensures immune evasion, prolonged circulation, and controlled therapeutic release triggered by tumor microenvironmental cues such as acidity, hypoxia, and elevated glutathione levels. It delivers oncogenic microRNA sponges, short-hairpin RNAs, tumor-specific antigens, and cyclin-targeting RNAs to enhance gene silencing, immune activation, and tumor suppression. This review examines the limitations of current delivery systems and presents VIBV as a promising next-generation strategy with improved biocompatibility, targeting precision, and potential for cost-effective, personalized cancer therapy, while also addressing its remaining challenges and prospects.

Harlequin ichthyosis, one of the rarest and most severe skin disorders, is mainly characterized by extreme hyperkeratosis, severely impairing the natural barrier function of the skin. This congenital disease results from a mutation in the ABCA12 gene responsible for lipid transport, whereby healthy skin development is assured. Harlequin ichthyosis is an autosomal recessive condition that requires parents to carry a defective gene copy for the disorder to manifest in their offspring. Babies born with Harlequin ichthyosis have thick skin plates that crack and flake off; they easily become dehydrated, infected, and may suffer from respiratory complications. With new improvements in neonatal care and systemic therapy, notably retinoid therapy, infants’ survival rates have improved. This review provides an inclusive overview of the pathophysiology, clinical features, diagnostic methods, management, and potential future therapies for Harlequin ichthyosis. In addition, a discussion on genetic counseling and its importance in managing family risk factors is also included, as well as a look into cutting-edge research focused on gene therapy and potential curative treatments.

The Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise and rename the 2019 “Chinese Guidelines on the Management of Liver Cirrhosis” to “Chinese Guidelines for Clinical Diagnosis, Treatment, and Management of Cirrhosis (2025)”. These updated guidelines are aimed at providing recommendations for the clinical diagnosis and management of liver cirrhosis across the compensated, decompensated, and recompensated stages, as well as guidance on cirrhosis reversal and associated complications.

Primary biliary cholangitis (PBC) is a chronic progressive autoimmune disorder characterized by small non-purulent intrahepatic bile duct destruction (ductopenia) and cholestasis. While the etiology of PBC remains unclear, it is believed to involve genetic-environmental interactions. Emerging evidence highlights gut microbiota dysbiosis in PBC patients, with increased symbiotic bacteria and decreased pathogenic bacteria. Microbial alterations potentially influence disease pathogenesis through multiple mechanisms, including immune dysregulation, intestinal barrier damage, BA metabolic dysregulation, and cholestasis. These findings suggest that the gut microbiota can serve not only as a non-invasive biomarker for diagnosis and prognosis evaluation but also as a therapeutic target for the disease. In this review, we summarize changes in PBC patients’ gut microbiota, explain how these changes affect disease occurrence and development, and discuss treatment methods with potential clinical value that intervene in gut microbiota.

Autoimmune hepatitis (AIH) is an inflammatory liver disease influenced by genetic, environmental, and immunologic factors. Individuals diagnosed with AIH may exhibit concurrent autoimmune manifestations affecting multiple organ systems. The prevalence of AIH associated with other autoimmune diseases has been reported to range from 20% to 40%. This review indicates that the associations between AIH and autoimmune thyroiditis, type 1 diabetes mellitus, ulcerative colitis, Crohn disease, and celiac disease appear to be significant. However, the associations between AIH and primary sclerosing cholangitis, primary biliary cholangitis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, and vitiligo are not well-supported. The aim of this review is to evaluate the strength of the reported associations between AIH and other autoimmune diseases, and to update and present the available evidence on their prevalence, proposed underlying pathogenic mechanisms, diagnostic considerations, and treatment approaches.

Aging is characterized by a progressive decline in physiological function, an increased risk of chronic diseases, and multiple molecular and cellular alterations, including inflammation, oxidative stress, and mitochondrial dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for the treatment of type 2 diabetes and obesity, may modulate pathways associated with the hallmarks of aging. This review aims to summarize the mechanistic and therapeutic evidence for GLP-1 RAs in targeting key aging processes and their potential to restore cellular homeostasis and enhance healthspan. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to August 2025. Both preclinical and clinical studies were included if they evaluated the effects of GLP-1 RAs on the major biological processes encompassed by the 12 hallmarks of aging, such as mitochondrial dysfunction, insulin resistance, dysbiosis, inflammaging, autophagy, proteostasis, and genomic stability. Data were analyzed narratively to elucidate potential mechanisms and translational relevance. Evidence from animal and human studies demonstrates that GLP-1 RAs improve mitochondrial function, reduce oxidative stress, attenuate chronic inflammation, and enhance autophagic activity. Additionally, they modulate nutrient-sensing pathways and metabolic processes, thereby improving cellular resilience. Preclinical studies indicate neuroprotective, cardioprotective, and hepatoprotective effects, while emerging clinical data support improvements in metabolic and inflammatory profiles in older adults. Taken together, GLP-1 RAs exert pleiotropic effects across all 12 hallmarks of aging. Although long-term safety and efficacy require further evaluation, current evidence positions GLP-1 RAs as promising therapeutic agents in translational geroscience, with the potential to mitigate age-related physiological decline and promote a longer, healthier lifespan.

The causal biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) and their clinical value remain unclear. In this study, we aimed to identify biomarkers for MASLD and evaluate their diagnostic and prognostic significance.

We conducted a Mendelian randomization analysis to assess the causal effects of 2,925 molecular biomarkers (from proteomics data) and 35 clinical biomarkers on MASLD. Mediation analysis was performed to determine whether clinical biomarkers mediated the effects of molecular biomarkers. The association between key clinical biomarkers and MASLD was externally validated in a hospital-based cohort (n = 415). A machine learning–based diagnostic model for MASLD was developed and validated using the identified molecular biomarkers. Prognostic significance was evaluated for both molecular and clinical biomarkers.

Six molecular biomarkers—including canopy FGF signaling regulator 4 (CNPY4), ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6), and major histocompatibility complex, class I, A (HLA-A)—and eight clinical biomarkers (e.g., serum total protein (STP)) were identified as causally related to MASLD. STP partially mediated the effect of HLA-A on MASLD (23.61%) and was associated with MASLD in the external cohort (odds ratio = 1.080, 95% confidence interval: 1.011–1.155). A random forest model demonstrated high diagnostic performance (AUC = 0.941 in training; 0.875 in validation). High expression levels of CNPY4 and ENTPD6 were associated with the development of and poorer survival from hepatocellular carcinoma. Low STP (<60 g/L) predicted all-cause mortality (HR = 2.50, 95% confidence interval: 1.22–5.09).

This study identifies six causal molecular biomarkers (e.g., CNPY4, ENTPD6, HLA-A) and eight clinical biomarkers for MASLD. Notably, STP mediates the effect of HLA-A on MASLD and is associated with all-cause mortality.

Ischemic stroke is a complex cerebrovascular disorder characterized by highly unpredictable outcomes influenced by patient-specific variables, including age, stroke severity, and preventable stroke-related complications such as infections. Analyses of clinical data have indicated a cumulative post-stroke infection rate of approximately 30%, with reported rates ranging from 5% to 65%. Post-stroke infections pose a significant challenge, as they not only increase the financial burden of stroke care but are also associated with adverse clinical outcomes, prolonged hospital stays, and a higher risk of stroke recurrence. The inflammatory response plays a pivotal role in the pathophysiology of ischemic stroke, encompassing the activation of inflammatory cells, the release of inflammatory mediators, and the engagement of inflammatory signaling pathways. Recent advances in molecular biology have facilitated the identification and investigation of numerous inflammation-related biomarkers. This article reviews the roles and mechanisms of key inflammatory biomarkers, including cytokines, chemokines, adhesion molecules, inflammation-related enzymes and mediators, receptors, signaling pathway molecules, and acute-phase proteins in the context of ischemic stroke, highlighting their significance in stroke pathophysiology and prognostic assessment. Additionally, in conjunction with the latest research advances, the article discusses novel biomarkers such as microRNAs and galectin-3, which are emerging as important tools in multiple domains, including diagnosis and treatment. Drawing on clinical diagnostic and therapeutic practices, this review analyzes the diagnostic and therapeutic roles of both novel and traditional biomarkers in the progression of ischemic stroke, following the temporal sequence from disease onset to prognosis. Finally, the article addresses the limitations of current research and offers perspectives on future directions, providing insights that may contribute to the advancement of precision medicine in the management of ischemic stroke.

Drug discovery is an exceptionally long and costly process, often taking over 10 years and costing billions of dollars. Despite these efforts, more than 90% of drug candidates fail, with most failures occurring during clinical trials due to issues related to efficacy, safety, or poor pharmacokinetics. A major contributor to these failures is biopharmaceutic barriers, including poor solubility, limited permeability, active efflux by transporters such as P-glycoprotein and breast cancer resistance protein, and extensive first-pass metabolism by CYP450 enzymes. These factors severely limit drug absorption and bioavailability, reducing therapeutic efficacy. Although traditional approaches, such as high-throughput absorption, distribution, metabolism, and excretion screening and improved chemical design, have achieved some progress, a major shift is now occurring through the use of in silico modeling, artificial intelligence (AI), and machine learning. These AI-driven tools enhance the prediction accuracy of absorption, distribution, metabolism, and excretion profiles, identify transporter interactions, and even simulate metabolic pathways. Additionally, modern formulation technologies, such as three-dimensional printing, lipid-based nanocarriers, and biodegradable delivery systems, are increasingly being integrated with AI-powered design platforms to personalize and optimize drug delivery. However, these promising advancements also raise regulatory and ethical concerns that must be addressed before widespread adoption. This review examines the major biopharmaceutic barriers responsible for drug development failures and explores how emerging AI-driven strategies and formulation innovations are being used to overcome these limitations. It also discusses current regulatory challenges and ethical considerations associated with adopting these technologies.