Cutting-edge biotherapeutics and advanced delivery strategies for the treatment of metabolic dysfunction-associated steatotic liver disease spectrum

Journal of Controlled Release, Год журнала: 2025, Номер 380, С. 433 - 456

Опубликована: Фев. 11, 2025

Язык: Английский

---

The multifaceted roles of macrophages in the transition from hepatitis to hepatocellular carcinoma: From mechanisms to therapeutic strategies

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер 1871(3), С. 167676 - 167676

Опубликована: Янв. 18, 2025

Язык: Английский

---

Protective role of ginsenoside Rg1 in the dynamic progression of liver injury to fibrosis: a preclinical meta-analysis

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 28, 2025

Background The pathological progression from liver injury to fibrosis is a hallmark of disease, with no effective strategies halt this transition. Ginsenoside Rg1 has demonstrated range hepatoprotective properties; however, systematic preclinical evidence supporting its therapeutic potential for and remains limited. Purpose. This study evaluated the efficacy underlying mechanisms ginsenoside in animal models fibrosis, providing basis future clinical investigation. Methods A review was conducted on studies published PubMed, Web Science, Embase databases up 1 August 2024, adhereing rigorous quality standards. methodological assessed using SYRCLE’s risk bias tool. Meta-analysis subgroup analysis were performed Revman 5.4 software, while publication through funnel plots Egger’s test STATA 15.0 software. Additionally, time-dose interval curve utilized assess dose-response relationship identify dose treating fibrosis. Results Twenty-four trials involving 423 animals included. findings indicated that significantly improved function markers (ALT AST), reduced indicators associated lowered fibrosis-related (α-SMA, HYP, PCIII). Furthermore, it exhibited beneficial effects mechanistic inflammation, oxidative stress, apoptosis, compared control group ( P < 0.05). Time-dose revealed between 4 800 mg/kg/d. Conclusion at 4–800 mg/kg/d mitigates via anti-inflammatory, antioxidative, anti-apoptotic pathways. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD 42024557878.

Язык: Английский

---

Investigation of the Theranekron Ameliorative Effect on Sepsis-Induced Hepatotoxicity via Inflammation and Oxidative Stress Pathways

Cell Biochemistry and Biophysics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Язык: Английский

---

Integrated Spheroid-to-Population Framework for Evaluating PFHpA-Associated Metabolic Dysfunction and Steatotic Liver Disease

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), particularly among pediatric populations, requires identification modifiable risk factors to control progression. Per- and polyfluoroalkyl substances (PFAS) have emerged as potential contributors damage; however, their role in the etiology MASLD remains underexplored. This study aimed bridge gap between human epidemiological data vitro experimental findings elucidate effect perfluoroheptanoic acid (PFHpA), a short chain, unregulated PFAS congener on development. Our analysis Teen-LABS cohort, national multi-site obese adolescents undergoing bariatric surgery, revealed that doubling PFHpA plasma levels was associated with an 80% increase (OR, 1.8; 95% CI: 1.3–2.5) based biospies. To further investigate underlying mechanisms, we used 3D spheroids single-cell transcriptomics assess hepatic metabolism. Integrative identified dysregulation common pathways both spheroid models, those involved innate immunity, inflammation, lipid We applied latent unknown clustering integrated (LUCID) model associations exposure, multiomic signatures, risk. results proteome profile significantly higher odds (OR = 7.1), whereas distinct metabolome lower 0.51), highlighting critical protein pathogenesis. A translational framework uncover molecular mechanisms PFAS-induced cohort adolescents. Identifying key for can guide development targeted prevention treatment.

Язык: Английский

---

Pathogenic Mechanisms of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Associated Hepatocellular Carcinoma

Cells, Год журнала: 2025, Номер 14(6), С. 428 - 428

Опубликована: Март 13, 2025

Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of deaths worldwide. The etiology HCC has now dramatically changed from viral hepatitis to metabolic dysfunction-associated steatotic liver disease (MASLD). main pathogenesis MASLD-related hepatic lipid accumulation hepatocytes, which causes chronic inflammation subsequent progression fibrosis. Chronic generates oxidative stress DNA damage in contribute genomic instability, resulting development HCC. Several molecular pathways are also linked MASLD. In particular, MAPK PI3K-Akt-mTOR upregulated MASLD, promoting survival proliferation cells. addition, MASLD been reported enhance patients with infection. Although there no approved medication for besides resmetirom USA, some preventive strategies onset Sodium-glucose cotransporter-2 (SGLT2) inhibitor, a class medications, exert anti-tumor effects on by regulating reprogramming. Moreover, CD34-positive cell transplantation improves fibrosis intrahepatic angiogenesis supplying various growth factors. Furthermore, exercise through an increase energy consumption as well changes chemokines myokines. this review, we summarize recent progress made pathogenic mechanisms MASLD-associated introduced new therapeutic preventing based

Язык: Английский

---

Aspartate aminotransferase-to-platelet ratio index as a novel predictor of early mortality in heat stroke patients: a multi-centre retrospective study

Annals of Medicine, Год журнала: 2025, Номер 57(1)

Опубликована: Март 15, 2025

Background The aspartate aminotransferase-to-platelet ratio index (APRI) is an effective non-invasive marker for chronic liver dysfunction. Given that heat stroke patients often suffer from poor prognosis due to multi-organ involvement, with injury and coagulation dysfunction being of particular concern, this study aims investigate whether APRI can comprehensively reflect in explore its relationship 28-day mortality.

Язык: Английский

---

Prevalence and prognostic significance of cachexia diagnosed by novel definition for Asian population among Chinese cirrhotic patients

Archives of Gerontology and Geriatrics, Год журнала: 2025, Номер unknown, С. 105833 - 105833

Опубликована: Март 1, 2025

Язык: Английский

---

Editorial: Preventing and treating liver diseases: medicinal and food plants, their metabolites as potential options

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 18, 2025

Liver disease is seriously endangering human health in the world. It has become leading cause of death word (Israelsen et al., 2024). The presence and progression liver fibrosis led by hepatic inflammation main predictor liver-related across entire spectrum steatotic diseases (Taru A combination recent advancements widely available biomarkers for early detection together with considerable therapeutic interventions offer possibility to reduce morbidity mortality patients (Dabrowska Thus, it urgent find safe effective drugs treat diseases. medicinal food plants have unique advantages terms safety compliance, which always been an important source finding new hepatoprotective (Xu Consequently, discovery natural products from great practical significance development drugs, safety, multi-targets, multi-pathways. We are deeply privileged compile this research topic Frontiers Pharmacology dedicated "preventing treating diseases: plants, their metabolites as potential options".The study Han al. discussed about effects a low-dose (0.6 g/kg) high-dose (1.2 zhuyu pill on cholestasis rat model induced naphthyl isothiocyanate (50 mg/kg). In study, serum biochemistry histopathology results were used evaluate effect pill, mRNA-Seq analysis was performed verified using real-time uorescence quantitative PCR.The GO, KEGG, GSEA analyses integrated identify mechanism Zhuyu impacted cholestatic rats.It found that significantly improved abnormal changes biochemical blood indexes rats, regulated pathways related bile lipid metabolism, including fatty acid retinol steroid hormone biosynthesis, alleviated inflammation, cholestasis, metabolism disorders.Relative expression essential genes Cyp2a1, Ephx2, Acox2, Cyp1a2, Cyp2c11, Sult2a1 qRT-PCR showed same trend mRNA-seq (Han 2023). Therefore, significant anti-cholestatic regulating pathways. These findings indicate novel promising prospect cholestasis.Rutaecarpine pentacyclic indolopyridoquinazolinone alkaloid, isolated Evodia rutaecarpa first time. variety ailments, headaches, gastrointestinal disorders, postpartum hemorrhage, amenorrhea, difficult menstruation, other Li made comprehensive description Rutaecarpine derivatives focusing diverse biological activities. review, modification aimed at seeking its better physicochemical properties more potency had extensively studied. exhibited pharmacological activities, anti-inflammatory, anti-atherogenic, anti-Alzheimer's disease, anti-tumor, anti-fungal activities via mechanisms, such inhibiting cyclooxygenase-2, acetylcholine, phosphodiesterase 4B, 5, or topoisomerases (Li This review gave insight into encourage further exploration Rutaecarpine.Nawaz reviewed approaches chronic hepatitis C. he critically assesseed landscape C virus treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal management herbal rooted complementary medicine. understanding genome, variations, pathogenesis, impact dietary, social, environmental, economic factors (Nawaz primarily focused intricate nature genomes explored botanical both preventing infections.Feng meta-analysis search relevant preclinical references multiple databases. Statistical conducted STATA, included use 3D maps radar charts display matrine dosage frequency hepatoprotection hepatotoxicity. demonstrated bidirectional ALT AST levels, also SOD, MDA, TG, TC, IL-6, TNF-α, CAT levels. Based three-dimensional analysis, optimal ranged 10 69.1 mg/kg. However, high protection low toxicity dose 20-30 mg/kg/d 0.02-0.86 weeks. molecular docking revealed interaction MT SERCA well SREBP-SCAP complexes. Matrine could alter Ca 2+ homeostasis injury pathways, SREBP1c/SCAP, Notch/RBP-J/HES1, IκK/NF-κB, Cul3/Rbx1/Keap1/Nrf2 (Feng 2024).The pericarp Herpetospermum pedunculosum traditionally jaundice hepatitis. Liu characterized total cucurbitacins extracted H. evaluated potential.Molecular networking based UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin E major components cucurbitacins, comprising 70.3%, 26.1%, 3.6% determined RP-HPLC, respectively. Total treatment reversed CCl4-induced metabolic associated damage dose-dependent manner, impacting energy oxidative stress phenylalanine superior efficacy HLSP. Safety evaluation safe, higher LD50 NOAEL values than 36.21 15 mg/kg body weight, respectively, while HLSP 14 weight (Liu summary, agent, warranting investigation synergistic individual components. Kim applied additive medicines lifestyle non-alcoholic disease. eight randomized controlled trials 603 participants study. Participants administered multi-herbal formulas single-herbal extracts along 12 improvement ultrasoundbased steatosis measured odds ratio medicine group those alone (OR = 7.9, 95% CI 0.7 95.2, p < 0.1). addition, decreased levels aspartate transferase (MD-7.5, CI-13.4 -1.7, 0.01) cholesterol (MD-16.0, CI-32.7 0.7, 0.06) (Kim 2024).To fruit plant Forsythia suspensa (Thunb.) Vahl inflammation-associated diseases, Zhou animal models probe signaling underlying inflammation. all data Review Manager 5.3 presented flow diagrams, risk-of-bias summaries, forest plots, funnel plots. As result, 11 records selected final 710 initial search. F. inflammatory cytokine antioxidant enzyme superoxide dismutase. effectively change acute indicators models, regulation channel proteins suggested good drug (Zhou 2024).Tiao Zhi decoction alcohol-associated Xie Zhuo Tiao alcohol-induced dysfunction, histological examinations parameters after 4-week administration.Mechanically, alcohol-stimulated ameliorated Zhi, accompanied Nrf2/Keap1 alcohol-activated phosphorylation pro-inflammatory transcription factors, JNK, P38, P65, IκBα, rescued (Chang alleviating injury, stress, possibly through modulation MAPKs/NF-κB suggesting option alcoholic disease.Elshaer deterioration NaNO2 additives hematology, profile, function, kidney function male Wistar supplementation Saussurea costus root ethanolic extract improve NaNO2-induced hepatorenal toxicity. NaNO2-treated organ weights, hematological parameters, immunohistochemical histopathological alterations.Furthermore, increase TNF-α tumor suppressor gene P53 liver, reduction detected anti-inflammatory IL-4 apoptosis BCL-2, compared control group. Interestingly, S. ability alleviate toxic architecture. Additionally, modulate cytokines apoptotic (Elshaer word, established mitigating modulating metabolic, inflammatory, apoptosis, underscored promise detoxifying counteract harmful impacts sodium nitrite.Libreville. Various calculated collected One-way ANOVA independent samples t-test statistical analyses.The survey 63 species belonging 35 families. Prevalent symptoms treated fever (18%), cough (16%), fatigue (13%), cold (12%). demographic highlighted 52.58% subjects (p > 0.94) aged 31-44 years enrolled survey, 48.45% 0.0001) 74.73% 0.99) informants university-level education. indicated 66% prophylaxis (34%), prevention (26%), exclusively (3%), only (3%) suffering COVID-19, against 34% who did not treatment. Annickia chlorantha, Citrus sp., Alstonia congensis, Zingiber officinale, Carica papaya emerged most commonly cited highest RFC (0.15-0.26), ) (Mounanga reinforced method COVID-19 symptoms, thereby advocating utilization managing coronavirus infections.NASH mechanisms C57BL/6J mice subjected methionineand choline-deficient diet. salidroside preventive NASH vivo, upregulate autophagy, downregulate rebalance immunity, exert anti-NASH properties. Finally, transcript-proteome sequencing, evaluation, experimental validation might targeting PPARα. regulate autophagy innate immunity adaptive PPAR pathway, SDS be future (Chu 2024).Chen mouse high-fat diet feeding weeks, gavaged Polygonatum cyrtonema ethanol (100, 300, 900 mg/kg/day), simvastatin (4 211 analysis. P. hepatocellular degeneration way. restored AMPK, SIRT1, SREBP1, PPAR-α mRNA protein RNAseq profiles response treatments. Ingenuity pathway RNA-seq key canonical upstream molecules (Chen 2025). confirmed underscores AMPK/SIRT1 theraputic target treatment.To hepatotoxic

Язык: Английский

---

Exercise and tissue fibrosis: recent advances in therapeutic potential and molecular mechanisms

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Март 20, 2025

Tissue fibrosis represents an aberrant repair process, occurring because of prolonged injury, sustained inflammatory response, or metabolic disorders. It is characterized by excessive accumulation extracellular matrix (ECM), resulting in tissue hardening, structural remodeling, and loss function. This pathological phenomenon a common feature the end stage numerous chronic diseases. Despite advent novel therapeutic modalities, including antifibrotic agents, these have only modest efficacy reversing established are associated with adverse effects. In recent years, growing body research has demonstrated that exercise significant benefits potential treatment fibrosis. The anti-fibrotic effects mediated multiple mechanisms, direct inhibition fibroblast activation, reduction expression pro-fibrotic factors such as transforming growth factor-β (TGF-β) slowing collagen deposition. Furthermore, been to assist maintaining dynamic equilibrium repair, thereby indirectly reducing damage can also help maintain balance improving disorders, exerting anti-inflammatory antioxidant effects, regulating cellular autophagy, restoring mitochondrial function, activating stem cell activity, apoptosis, alleviating tissue. paper presents review its underlying mechanisms for range fibrosis, cardiac, pulmonary, renal, hepatic, skeletal muscle. offers valuable reference point non-pharmacological intervention strategies comprehensive fibrotic

Язык: Английский

---