Metabolic dysfunction-associated fatty liver disease (MAFLD) poses a significant challenge in modern medicine due to its high prevalence. The pathogenesis of MAFLD involves a complex dysmetabolic process consistent with the “multiple-hit” hypothesis. This process includes excessive triglyceride (TC) accumulation within hepatocytes, lipotoxicity, insulin resistance (IR), chronic low-grade inflammation, and increased oxidative stress. The role of leptin in the liver has been extensively studied, demonstrating both direct effects on hepatic cells and indirect actions mediated through the central nervous system (CNS). In MAFLD, leptin modulates several physiological processes: it improves glucose metabolism by enhancing insulin sensitivity and lowering glucose levels; regulates lipid metabolism by promoting β-oxidation and TC export while inhibiting lipogenesis; and contributes to fibrogenesis by upregulating transforming growth factor-β (TGF-β) expression and activating hepatic stellate cells (HSCs) and the immune response. This review explores the structure of leptin, its primary physiological functions, its potential role in MAFLD pathogenesis, and its promise as a novel therapeutic target.

Circular RNAs (circRNAs) are non-coding RNAs characterized by a strictly closed-loop covalent structure. They are abundantly detected in various cells due to their conserved nature. Studies have reported their potential association with chronic liver disease (CLD), including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), with possible roles as diagnostic and prognostic markers. This study aimed to analyze the potential use of serum-derived hsa_circ_101555 as a diagnostic tool for CLD without HCC, and to compare it with other known non-invasive parameters for liver disease severity and inflammation. Additionally, it aimed to evaluate its expression among non-HCC CLD patients, CLD with HCC cases reported in our published (phase I) study, and healthy controls.

A cross-sectional study (phase II) was conducted involving 30 clinically, laboratory, and radiologically diagnosed Egyptian non-HCC CLD patients and 30 healthy subjects. The serum expression level of hsa_circ_101555 was measured using real-time polymerase chain reaction. The diagnostic accuracy was assessed through receiver operating characteristic curve analysis, calculating the area under the curve to determine sensitivity and specificity. The study also compared hsa_circ_101555 levels with established non-invasive parameters such as the Child-Turcotte-Pugh and model for end-stage liver disease scores, as well as inflammatory markers like the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

hsa_circ_101555 demonstrated high diagnostic accuracy (area under the curve of 0.970) at a cutoff point of 2.088 for differentiating non-HCC CLD patients from healthy controls. Elevated circRNA levels were noted in patients with hepatic encephalopathy and ascites, correlating with advanced liver disease scores (Child-Turcotte-Pugh/model for end-stage liver disease scores). Mean circRNA values were highest in HCC cases, followed by non-HCC CLD patients, and lowest in healthy controls.

Serum-derived hsa_circ_101555 demonstrates high diagnostic accuracy in differentiating non-HCC CLD patients from healthy controls. These findings suggest that hsa_circ_101555 has the potential to serve as a reliable non-invasive biomarker for the early diagnosis of CLD, correlating with disease severity and inflammation markers. Further research with larger sample sizes is warranted to validate its clinical utility and enhance the management of CLD.

Globally, the integration of traditional medicine and modern medicine has been recognized as a global health priority aimed at improving healthcare accessibility, cultural relevance, and therapeutic effectiveness. This review systematically examines the global landscape of traditional medicine-modern medicine integration by analyzing policy developments, regulatory frameworks, and clinical implementation models across various regions, including Asia, Africa, Europe, and the USA. The scope of the review encompasses five key domains: (1) global policy initiatives, (2) regulatory and institutional frameworks, (3) clinical integration models, (4) impacts and outcomes of integrative practices, and (5) challenges and barriers to implementation. Based on peer-reviewed literature and official health policy documents published between 2000 and 2025, the present review investigates how countries have operationalized clinical integration models combining traditional and complementary medicine. Although interest in traditional and complementary medicine has grown worldwide, persistent challenges, such as limited scientific validation, lack of standardization, and professional resistance, continue to hinder progress. This review concludes that successful and sustainable integration requires evidence-based clinical approaches, inclusive regulatory reforms, and coordinated policy strategies. Countries such as China, India, and Brazil have made significant advances, offering valuable models for future implementation worldwide.

Ginseng, a traditional Chinese medicinal herb, has been used for centuries to enhance vitality and overall well-being. This review synthesizes multiple studies to summarize the latest discoveries on the immunoregulatory effects of ginseng, its role in improving patients’ quality of life, and new evidence of its antitumor properties. It concludes that ginseng and its extracts can improve patients’ quality of life and may have the potential to target tumor cells. Meanwhile, ginseng extracts significantly improve sub-health status, with an 85% improvement rate observed in young adults after 30 days of intervention. This review provides valuable new evidence for ongoing research on ginseng and its extracts.

Further decompensation in cirrhosis is associated with increased mortality. However, reliable tools to predict further decompensation after transjugular intrahepatic portosystemic shunt (TIPS) are currently limited. This study aimed to investigate the incidence and risk factors of further decompensation within one year post-TIPS in patients with cirrhosis and to develop a predictive model for identifying high-risk individuals.

This retrospective cohort study enrolled 152 patients with cirrhosis undergoing TIPS for variceal bleeding and/or refractory ascites (January 2018–January 2024). Patients were stratified according to one-year decompensation outcomes. LASSO regression and multivariable logistic analysis were used to identify predictors, and a nomogram was constructed and internally validated using bootstrapping (1,000 replicates).

Among the 152 patients (median age 57.5 years [IQR 50.0–66.0]; 58.6% male; 58.6% viral/alcohol-associated etiology), 65.8% (100/152) achieved clinical stability at one year post-TIPS, while 34.2% (52/152) developed further decompensation. LASSO regression identified right hepatic lobe volume, spleen volume, and portal pressure gradient (PPG) reduction as key predictors, all independently associated with further decompensation risk in multivariable analysis (OR [95% CI]: 0.683 [0.535–0.873], 1.435 [1.240–1.661], and 0.961 [0.927–0.996], respectively). The nomogram demonstrated superior discrimination compared with PPG reduction alone and benchmark prognostic scores (AUC 0.854 [0.792–0.915] vs. 0.619–0.652; ΔAUC +0.201–+0.235, p < 0.001) with 92.3% sensitivity. High-risk patients (score > 86) had a 10.7-fold higher risk of further decompensation than low-risk patients (60.0% vs. 5.6%; p < 0.0001).

This validated model, combining hepatosplenic volumetry and PPG reduction, accurately stratifies further decompensation risk post-TIPS and may guide targeted surveillance and preventive interventions.

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most common chronic liver disorder worldwide, results from multidimensional network dysregulation involving lipid metabolism imbalance, insulin resistance, oxidative stress, chronic inflammation, and gut-liver axis disruption. Silent information regulator 1 (SIRT1), an NAD+-dependent deacetylase, functions as a central regulator of metabolic homeostasis and a key mediator in immune microenvironment remodeling and inter-organ communication. This review systematically describes the multi-target mechanisms of SIRT1 in MASLD pathogenesis through its regulation of critical factors, including peroxisome proliferator-activated receptor gamma coactivator 1-α, Forkhead Box O, and nuclear factor kappa-light-chain-enhancer of activated B cells, which govern hepatocyte lipid remodeling, mitochondrial quality control, autophagy–endoplasmic reticulum stress balance, and Kupffer cell/T cell polarization. This work introduces, for the first time, the concept that SIRT1 mediates systemic regulation of MASLD via coordinated “metabolism–inflammation–organ axis” interactions. Recent studies indicate that natural compounds (e.g., resveratrol, curcumin) improve gut-liver barrier function through microbiota–SIRT1 interactions, while synthetic activators (SRT1720) and NAD+ precursors (NMN) enhance hepatocyte antioxidant capacity and fatty acid β-oxidation. This innovative analysis highlights the spatiotemporal specificity of various SIRT1 activators, emphasizing that tissue-selective delivery and dynamic dosage optimization are crucial for overcoming clinical translation challenges. By integrating mechanistic and translational insights, this review provides a novel foundation for precision intervention strategies targeting SIRT1 network reprogramming.

Persistent liver injury halts the regenerative capacity of hepatocytes and activates mechanisms that result in the replacement of normal hepatic parenchyma with extracellular matrix deposits. As liver fibrosis develops, the liver undergoes architectural changes and alterations in microcirculation that lead to increased intrahepatic vascular resistance and portal hypertension. Thrombocytopenia is a prevalent condition in patients with chronic liver disease and portal hypertension. Multiple mechanisms related to increased platelet destruction or decreased platelet production contribute to thrombocytopenia. Increased platelet destruction occurs due to splenic sequestration caused by hypersplenism or immune-mediated conditions. Decreased platelet production results from a decline in thrombopoietin production, bone marrow suppression by medications, or toxic insults. Therapies aimed at improving thrombocytopenia are controversial, and individual factors must be considered. Although hepatic venous pressure gradient measurement is the gold standard for diagnosing portal hypertension, non-invasive tests show adequate correlation with hepatic venous pressure gradients. Various clinical risk scores consider platelet counts as independent predictors of adverse liver outcomes, such as the development of esophageal varices and the presence of advanced fibrosis. Nonselective beta-blockers are the cornerstone of long-term management for clinically significant portal hypertension. Indications for transjugular intrahepatic portosystemic shunt placement include failure to control portal hypertension-related bleeding, early rebleeding, and refractory or recurrent ascites. Ultimately, liver transplantation is the only definitive cure for portal hypertension and its major complications, including thrombocytopenia. Understanding the mechanisms underlying thrombocytopenia in patients with portal hypertension and chronic liver disease is essential for accurate diagnosis and effective patient management. This review aimed to evidence on the pathophysiological mechanisms linking chronic liver disease, portal hypertension, and thrombocytopenia, and to discuss their diagnostic and therapeutic implications.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an escalating healthcare burden across the Middle East and North Africa (MENA) region; however, system-level preparedness remains largely undefined. This study aimed to assess existing models of care, clinical infrastructure, policy frameworks, and provider perspectives across 17 MENA countries.

A cross-sectional, mixed-methods survey was distributed to clinicians from MASLD-related specialties across the region. A total of 130 experts (87.2% response rate) from academic, public, and private sectors in 17 countries participated. The questionnaire addressed national policies, diagnostic and therapeutic practices, referral pathways, multidisciplinary team (MDT) integration, and patient/public engagement. Quantitative responses were analyzed descriptively, while qualitative inputs underwent thematic analysis.

Only 35.4% of respondents confirmed the presence of national clinical guidelines for MASLD, and 73.1% reported the absence of a national strategy. Structured referral pathways were reported by 39.2% of participants, and only 31.5% believed the current model adequately addresses MASLD. While 60% supported MDT approaches, implementation remained inconsistent. Limited access to transient elastography was reported by 26.2% of providers. Public education efforts were minimal: 22.3% reported no available tools, and 87.7% indicated the absence of patient-reported outcomes data. Nearly half (47.7%) cited poor patient adherence, attributed to low awareness, financial barriers, and lack of follow-up.

Significant policy, structural, and educational gaps persist in MASLD care across the MENA region. To address this rising burden, countries must adopt integrated national strategies, expand access to non-invasive diagnostic tests, institutionalize MDT care, and invest in both public and provider education as essential pillars of system-wide preparedness.

Sclerocarya birrea (A. Rich) Hochst (Anacardiaceae) is a plant widely used by traditional healers in several African countries to treat numerous illnesses such as Alzheimer’s disease, schizophrenia, inflammation, infections, arterial hypertension, headaches, and others. This study aimed to determine the therapeutic efficacy of Sclerocarya birrea (S. birrea) against glutamate-induced neurotoxicity.

Thirty naïve white mice (Mus musculus Swiss, Muridae), of both genders and weighing between 18 and 25 g, were used in the experiments. Different doses (102.5, 205, and 410 mg/kg) of the extract and vitamin C (100 mg/kg) were administered to the animals one hour before administration of monosodium glutamate (4 mg/kg) for 15 consecutive days. T-maze and Y-maze tests were conducted over three days to assess the animals’ behavioral performance. After behavioral testing, the animals were sacrificed and their brains removed for analysis of oxidative stress parameters.

S. birrea extract reversed glutamate-induced behavioral alterations by significantly (P < 0.001) reducing the latency to reach the platform in the T-maze and significantly increasing the percentage of spontaneous alternation in the Y-maze. The extract also significantly counteracted (P < 0.001) glutamate-induced oxidative stress parameters. The 102.5 and 205 mg/kg doses of the extract significantly (P < 0.001) reduced catalase and reduced glutathione levels, as well as the increase in malondialdehyde levels induced by glutamate.

S. birrea root bark extract exhibits neuroprotective properties that facilitate memory and ameliorate glutamate-induced cognitive deficits in white mice. The results provide partial justification for the traditional medicinal use of S. birrea extract.

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.

Portal vein thrombosis (PVT) frequently occurs in patients with porto-sinusoidal vascular disease (PSVD), but its clinical characteristics and outcomes remain poorly understood. This study aimed to investigate the clinical features and outcomes of PVT in PSVD.

A total of 169 patients with PSVD confirmed by hepatic histology were included. PVT was diagnosed using contrast-enhanced magnetic resonance imaging or computed tomography. Demographic, clinical, and laboratory data, portal hypertension-related complications, comorbidities, and mortality were collected and compared between patients with and without PVT. The primary outcomes were baseline clinical characteristics and liver-transplantation-free mortality; the secondary outcome was the dynamic changes of PVT during follow-up.

At baseline, 45 (26.6%) PSVD patients had PVT. Compared to those without PVT, patients with PVT had significantly higher rates of esophageal variceal bleeding (62.2% vs. 29.0%), ascites (73.3% vs. 35.5%), antithrombin III deficiency (78.1% vs. 38.4%) (all p < 0.001), and a history of hematological disorders (11.1% vs. 0.8%, p = 0.005). After a median follow-up of 40.1 (23.4–62.3) months, liver-transplantation-free mortality rates were 7.9% (3/38) and 1.8% (2/112) in patients with and without PVT, respectively (log-rank p = 0.110). Among 41 patients followed for a median of 17.1 (7.4–39.3) months, PVT resolved in 9.1% (1/11) of those with baseline PVT and developed in 13.3% (4/30) of those without PVT at baseline. The one- and two-year cumulative incidence rates of PVT were 3.3% and 6.7%, respectively.

PSVD patients with PVT experience more portal hypertension-related complications, complex coagulation profiles, hematological disorders, and a higher risk of death compared to those without PVT.

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.

Metabolic dysfunction-associated steatohepatitis (MASH) represents a critical step in the progression from simple fatty liver disease to more severe conditions such as cirrhosis and hepatocellular carcinoma, and it remains difficult to treat. Arctigenin (ATG), a monomer of Fructus Arctii, exhibits anti-inflammatory activity. Therefore, we aimed to examine its potential protective role against MASH and explore the underlying mechanisms.

Male C57BL/6 mice were divided into four groups: control, MASH, low-dose ATG (30 mg/kg/day), and high-dose ATG (120 mg/kg/day). MASH was induced through a choline-deficient, L-amino acid-defined high-fat diet for eight weeks, with concurrent preventive ATG administration. Liver injury, lipid metabolism, inflammation, oxidative stress, and fibrosis were assessed. Network pharmacology was employed to identify the potential protective mechanisms of ATG. Key factors were evaluated in vitro to verify the ATG targets.

ATG administration prevented the progression of MASH in a dose-dependent manner. High-dose ATG significantly reduced hepatic macrophage and neutrophil infiltration, serum enzyme levels, and lipid peroxidation, while enhancing antioxidant enzyme activity. Mechanistic network pharmacology identified modulation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome as the central pathway underlying ATG’s bioactivity. Functional analyses in lipopolysaccharide-stimulated RAW264.7 cells confirmed that ATG inhibited NLRP3 expression, pyroptosis-related protein cleavage (hereinafter referred to as GSDMD-N), and pro-inflammatory chemokine production in a concentration-dependent manner. Notably, ATG disrupted NLRP3/GSDMD-N axis activity in macrophages without causing cellular toxicity.

ATG may inhibit the inflammatory cascade primarily by targeting macrophage NLRP3 inflammasomes, thereby preventing the progression of MASH.

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.

Regular exercise is fundamental for people with metabolic dysfunction-associated steatotic liver disease (MASLD), yet exercise maintenance is generally poor. This generative co-design process aimed to embed the voices and opinions of people with lived experience of MASLD and their care stakeholders to (i) frame barriers and enablers to exercise maintenance and (ii) highlight priorities for exercise-focused research agendas in MASLD.

A generative co-design framework was applied. Two virtual co-design sessions were undertaken: Session 1 – Framing the issue, where initial discovery was conducted with people with lived experience of MASLD; and Session 2 – Generative design and sharing ideas with lived experience partners and healthcare stakeholders. Sessions were audio-recorded and transcribed, and key determinants and considerations were discerned by two independent researchers.

Lived experience partners (n = 5, 53 ± 16 years, 40% male) ranked five equally important barriers to exercise maintenance: musculoskeletal and pain issues, lack of access to exercise equipment/facilities, cost, competing priorities, and low energy levels, which influenced core positive and negative determinants. Alongside lived experience partners, healthcare stakeholders (hepatologists [n = 3], exercise professionals [n = 3], 67% male) identified three core needs with eight considerations. Some disconnects in priorities were observed. Lived experience partners emphasized affordability, accessibility, and considerations for comorbidities, while healthcare partners advocated for research on natural history, prevention, behavior change, cost-effectiveness, and health system change.

This co-design methodology highlights unique consumer-informed research questions. Exercise interventions and their associated implementation trials will benefit from being co-designed with both people with MASLD and care stakeholders.