Search Results (3,208)

Background: Acute pancreatitis (AP) is characterized by the abnormal activation of pancreatic enzymes due to various causes, leading to local pancreatic inflammation. This can trigger systemic inflammatory response syndrome and multi-organ dysfunction. Hyperlipidemia, mainly resulting from lipid metabolism disorders and elevated triglyceride levels, is a major etiological factor in AP. This study aims to investigate the role of lipid metabolism-related genes in the pathogenesis of AP and to propose novel strategies for its prevention and treatment. Methods: We obtained AP-related datasets GSE3644, GSE65146, and GSE121038 from the GEO database. Differentially expressed genes (DEGs) were identified using DEG analysis and gene set enrichment analysis (GSEA). To identify core lipid metabolism genes in AP, we performed least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) analysis. Gene and protein interactions were predicted using GeneMANIA and AlphaFold. Finally, biomarker expression levels were quantified using Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) in an AP mouse model. Results: Seven lipid metabolism-related genes were identified as key biomarkers in AP: Amacr, Cyp39a1, Echs1, Gpd2, Osbpl9, Acsl4, and Mcee. The biological roles of these genes mainly involve fatty acid metabolism, cholesterol metabolism, lipid transport across cellular membranes, and mitochondrial function. Conclusions: Amacr, Cyp39a1, Echs1, Gpd2, Osbpl9, Acsl4, and Mcee are characteristic biomarkers of lipid metabolism abnormalities in AP. These findings are crucial for a deeper understanding of lipid metabolism pathways in AP and for the early implementation of preventive clinical measures, such as the control of blood lipid levels. Full article

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant metabolic disorder in modern poultry production, particularly affecting high-yielding laying hens. This condition compromises bird welfare, productivity, and economic sustainability within commercial farming systems. This narrative review provides a comprehensive overview of the underlying mechanisms through which hepatic lipid accumulation, metabolic dysfunctions, hormonal imbalances, genetic susceptibilities, and environmental stress contribute to the development of NAFLD. The multifactorial nature of NAFLD is explored through a critical assessment of the literature, highlighting the influence of diet composition, management practices, and physiological demands associated with intensive egg production. Emphasis is placed on recent advancements in nutritional modulation, selective breeding, and housing improvements aimed at prevention and mitigation of NAFLD. Furthermore, the review identifies key research gaps, including limited understanding of epigenetic influences and the long-term efficacy of intervention strategies. An integrative framework is advocated, synergizing genetics, nutrition, and environmental optimization to effectively address the complexity of NAFLD in poultry and supports the development of resilient production systems. The insights presented aims to inform both future research and practical applications for enhancing poultry health and performance. Full article

Extracellular vesicles (EVs) are mediators of intercellular communication and serve as promising tools for drug discovery and targeted therapies. These lipid bilayer-bound nanovesicles facilitate the transfer of functional proteins, RNAs, lipids, and other biomolecules between cells, thereby influencing various physiological and pathological processes. This review outlines the molecular mechanisms governing EV biogenesis and cargo sorting, emphasizing the role of key regulatory proteins in modulating selective protein packaging. We explore the critical involvement of EVs in various disease microenvironments, including cancer progression, neurodegeneration, and immunological modulation. Their ability to cross biological barriers and deliver bioactive cargo makes them desirable candidates for precise drug delivery systems, especially in neurological and oncological disorders. Moreover, this review highlights advances in engineering EVs for the delivery of RNA therapeutics, CRISPR-Cas systems, and targeted small molecules. The utility of EVs as diagnostic tools in liquid biopsies and their integration into personalized medicine and companion diagnostics are also discussed. Patient-derived EVs offer dynamic insights into disease states and enable real-time treatment stratification. Despite their potential, challenges such as scalable isolation, cargo heterogeneity, and regulatory ambiguity remain significant hurdles. Recent studies have reported novel pharmacological approaches targeting EV biogenesis, secretion, and uptake pathways, with emerging regulators showing promise as drug targets for modulating EV cargo. Future directions include the standardization of EV analytics, scalable biomanufacturing, and the classification of EV-based therapeutics under evolving regulatory frameworks. This review emphasizes the multifaceted roles of EVs and their transformative potential as therapeutic platforms and biomarker reservoirs in next-generation precision medicine. Full article

Exposure to persistent organic pollutants such as 2,3,7,8-tetrachlorodibenzodioxin (TCDD) increases metabolic disorder risk. In this study, we show that a single intraperitoneal injection of TCDD (10 μg/kg) in C57BL/6J mice induced body weight gain, lipid accumulation in the liver and adipose tissue, macrophage infiltration, and elevated hepatic and serum triglyceride levels after 12 weeks. Despite serum aryl hydrocarbon receptor (AhR) ligand levels normalizing by 12 weeks, the persistent effects suggest TCDD sequestration in fat tissue. TCDD inhibited the expression of mitochondrial proteins (COX1, TOM20, TFAM, H2AX) and reduced mitochondrial oxygen consumption. Liver-specific AhR knockout ameliorated TCDD-induced mitochondrial dysfunction, lipid accumulation, and macrophage infiltration. Mechanistically, TCDD-induced hepatic plasminogen activator inhibitor-1 (PAI-1) promoted adipocyte hypertrophy. In the liver, PAI-1 disrupted the interaction between tissue-type plasminogen activator (tPA) and apolipoprotein B (ApoB), thereby enhancing very-low-density lipoprotein (VLDL) assembly. These findings reveal that hepatocyte-derived circulating PAI-1, upregulated via hepatic AhR activation, contributes to adipocyte hypertrophy and hepatosteatosis through the intracellular modulation of the tPA–PAI-1 axis. Thus, hepatic AhR activation drives mitochondrial dysfunction and obesity, even after a single TCDD exposure. Full article

The complex pathological mechanisms of atherosclerosis (AS) involve lipid metabolism disorders, inflammatory responses, and plaque instability, resulting in significant challenges to effective clinical management. Current therapeutic approaches, such as statins and stent implantation, suffer from issues including single-target action, notable side effects, and the risk of restenosis. Nanoparticle-based drug delivery systems have demonstrated considerable promise by enabling the codelivery of multiple agents directly to atherosclerotic lesions, thereby improving therapeutic efficacy and minimizing systemic toxicity. Among various nanomaterials, organic nanoparticles have recently emerged as a research hotspot in the field of AS treatment due to their excellent biocompatibility, degradability, and potential for targeted modification. This review systematically summarizes the recent advances and emerging trends in the application of organic nanoparticles for AS treatment, employing bibliometric analysis to delineate research frontiers. We employed bibliometric tools to analyze 1999 articles on organic nanocarriers for AS therapy indexed in the Web of Science Core Collection. The analysis included co-occurrence and clustering techniques to explore influential keywords and key contributors. Temporal analysis was applied to identify emerging research hotspots and track the evolution of this field. The literature reveals three major current focal areas: (1) the development of engineered biomimetic organic nanoparticles; (2) the design of multifunctional polymer-based organic nanocarriers; and (3) the innovation of organic-coated stents. This article not only provides a comprehensive overview of cutting-edge organic nanotechnologies for AS therapy, but also critically discusses the challenges in clinical translation, offering insights into future directions for the development of safe, effective, and personalized nanomedicine strategies against AS. Full article

Metabolic syndrome refers to a group of conditions that commonly occur together, including abdominal obesity, high blood pressure, elevated blood sugar, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL). These factors collectively increase the risk of cardiovascular disease, diabetes, and cognitive impairment. Recent research has identified a connection between metabolic syndrome and cognitive disorders such as mild cognitive impairment and vascular dementia (VaD). Mulberry (Morus alba L.) is a natural source of bioactive compounds with antioxidant, anti-inflammatory, and lipid-regulating properties. This meta-analysis assessed the potential of mulberry extract as an adjunctive treatment for metabolic risk factors linked to vascular dementia. We systematically reviewed randomized controlled trials (RCTs) published up to May 2025 that compared mulberry extract to placebo or standard care in adults with metabolic disorders. Fifteen trials including 1202 participants met the inclusion criteria. The primary outcomes were fasting glucose, fasting insulin, liver enzyme levels, lipid profiles, and inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). The pooled results indicated that mulberry supplementation improved blood sugar control and lowered total cholesterol, low-density lipoprotein cholesterol (LDL), triglycerides, fasting blood glucose, glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), and inflammatory markers. Aspartate aminotransferase (AST) improved, whereas alanine aminotransferase (ALT) showed no significant change. Subgroup analyses revealed that greater benefits were associated with shorter treatment durations and doses below 500 milligrams per day. Furthermore, extracts from different parts of the mulberry plant showed varying effects on lipid and glucose metabolism. None of the included trials directly measured cognitive or neurovascular outcomes, so any potential neurovascular protection is inferred from changes in metabolic and inflammatory markers rather than demonstrated. In summary, these findings suggest that mulberry extract may be a promising complementary approach for managing metabolic risk factors in people at risk for VaD. However, further large-scale and rigorously designed studies are required to confirm its clinical benefits and to identify the most effective preparations. Full article

Parkinson’s disease (PD) is recognized as one of the most common neurodegenerative disorders globally. The primary factor contributing to this condition is the loss of dopaminergic neurons, which results in both motor and nonmotor symptoms. The etiology of neurodegeneration remains unclear. However, it is characterized by the elevated production of reactive oxygen species, which subsequently leads to oxidative stress, lipid peroxidation, mitochondrial dysfunction, and inflammation. The investigation of the applicability of natural compounds and their derivatives to various diseases is becoming increasingly important. The possible role of curcumin from Curcuma longa L. and its derivatives in the treatment of PD has been partially investigated, but there are no data on the action of synthetic cyclic C₅-curcuminoids and chalcones tested in a Parkinson’s model. Two chalcones and five synthetic cyclic C₅-curcuminoids with potential antioxidant properties were investigated in an in vitro model of 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in differentiated SH-SY5Y cells. Reactive oxygen species (ROS) production, total antioxidant capacity, antioxidant enzyme activity, thiol and ATP levels, caspase-3 activity, and cytokine release were examined after treatment with the test compounds. Based on these results, one cyclic chalcone (compound 5) and three synthetic cyclic C₅-curcuminoids (compounds 9, 12, and 13) decreased oxidative stress and apoptosis in our in vitro model of neurodegeneration. Compounds 5 and 9 were also successful in decreasing the production of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α), while promoting the release of anti-inflammatory cytokines (IL-4 and IL-10). These findings indicate that these two compounds exhibit potential antioxidant, anti-apoptotic, and anti-inflammatory properties, rendering them promising candidates for drug development. Full article

Plant-derived compounds offer immense therapeutic potential, yet many suffer from limited solubility, instability, and poor bioavailability, restricting their clinical application. Curcumin, a polyphenol extracted from Curcuma longa, is one such molecule, with proven antioxidant and anti-inflammatory properties. To overcome its pharmacokinetic limitations, we developed Jamamina, a sustainable nanostructured lipid carrier (NLC) system incorporating curcumin and a Natural Deep Eutectic Solvent (NaDES) phase composed of malic acid and betaine. The bioinspired formulation, based on Amazonian tucumã butter and jambu oil, achieved high encapsulation efficiency (>80%) and curcumin amorphization, enhancing solubility and colloidal stability. In vitro assays with L132 demonstrated potent antioxidant activity (DPPH), a significant reduction in pro-inflammatory cytokines (TNF-α and IL-6), and upregulation of IL-10. The system also suppressed MMP-2/9 activity and preserved cytoskeletal integrity under oxidative stress. These findings highlight Jamamina as a multifunctional, eco-friendly nanoplatform that enables the pharmacological application of plant-derived curcumin, representing a promising platform for modulating redox balance and investigating inflammation in epithelial-like contexts. Full article

Lipids, together with water and proteins, constitute the essential structure of cell membranes, and in the CNS, critically contribute to the production, function, and maintenance of the myelin sheath. Myelin produced by oligodendrocytes (OLs) acts as an electric insulator and assures proper conduction of information. Three major fractions of myelin lipids are cholesterol, phospholipids, and glycolipids. These lipids not only sculpt the myelin landscape as a structural support for proteins, but they also play a crucial role in molecular interactions underlying processes of protein trafficking and signal transductions. The high lipid content of myelin makes it susceptible to lipid metabolism disorders. Disorders in systemic and local lipid metabolism may lead to loss of myelin integrity and stability, and potentially to CNS demyelination seen in neurodegenerative diseases, notably progressive multiple sclerosis, for which there are few effective therapies. Precise interactions among disorders in lipid metabolism, function of oligodendrocytes, and demyelination/remyelination events, including de novo myelin formation and myelin remodeling processes, may lay the foundation for novel therapeutics for progressive MS and other demyelinating CNS conditions. Full article

Peroxisomes are cellular organelles involved in multiple metabolic processes, including lipid oxidation, lipid synthesis, and the metabolism of reactive oxygen species. Peroxisomal disorders arise from defects in peroxisomal biogenesis or peroxisomal enzymes. Patients with severe peroxisomal disorders often present with a range of distinctive physical features and congenital malformations, such as neuronal migration defects, renal cysts, and bony stippling in the patellae and long bones. Liver disease has also been reported in some patients with peroxisomal biogenesis disorders, although the exact molecular mechanisms underlying its development remain unclear. Metabolic dysfunction-associated steatotic liver disease (MASLD) is now recognised as one of the most prevalent causes of chronic liver disease globally, due to its widespread incidence and potential for serious complications. This review aims to highlight the possible involvement of peroxisomal defects in the pathogenesis of MASLD. Full article

Objective: Insulin resistance (IR) is a complex and multifactorial disorder that contributes to type 2 diabetes and cardiovascular disease. MicroRNAs (miRNAs) play important roles in diverse developmental and disease processes. However, the molecular mechanisms of IR are unclear. This paper aims to explore the role of miRNA in regulating IR and to elucidate the mechanisms responsible for these effects. Methods: IR models were created by feeding a high-fat diet (HFD) to mice or stimulating 3T3-L1 cells with palmitate. Twelve weeks of HFD trigger weight gain, leading to lipid accumulation and insulin resistance in mice. The expression profiles of miRNAs in adipose tissues (AT) from the HFD-induced mouse models were analyzed. The relationship between miR-221-3p and SOCS1 was determined using dual luciferase reporter gene assays. Metabolic alterations in AT were investigated by real-time PCR and Western blot. Results: miR-221-3p was significantly increased in AT. HFD-induced disturbances in glucose homeostasis were aggravated by miR-221-3p upregulation. The inhibition of miR-221-3p promoted insulin sensitivity including reduced lipid accumulation and the disruption of glucose metabolism. Of note, the 3′-UTR of SOCS1 was found to be a direct target of miR-221-3p. The SOCS1 inhibitor attenuated miR-221-3p-induced increases in IRS-1 phosphorylation, AKT phosphorylation, and GLUT4. miR-221-3p was considered to be involved in the PI3K/AKT signaling pathway, thus leading to increased insulin sensitivity and decreased IR in HFD-fed mice and 3T3-L1 adipocytes. Conclusions: The miR-221-3p/SOCS1 axis in AT plays a pivotal role in the regulation of glucose metabolism, providing a novel target for treating IR and diabetes. Full article

Myokines are secreted by muscle and play crucial roles in muscle repair and regeneration and also impact diverse physiological effects through crosstalk with other metabolic organs. However, aging is associated with a progressive decline in muscle mass, which in turn leads to reduced myokine secretion. This decline may contribute to the development of sarcopenia, leading to an increased risk of metabolic disorders such as type 2 diabetes. Accordingly, interest in identifying novel myokines and elucidating their biological functions is increasing. In this study, we explored the function of biglycan (BGN), a novel myokine, in aging-related metabolic tissues. BGN levels decreased in the muscle tissue and plasma of older adults and aged mice, whereas exercise intervention restored BGN expression in aged mice. BGN counteracted the expression of atrophy-related genes involved in muscle degradation and mitigated muscle mass loss by regulating AKT/mTOR signaling pathway. Notably, BGN decreased the expression of the senescence marker p21 and senescence-associated secretory phenotype (SASP)-related genes in hepatocytes. Additionally, BGN attenuated senescence-induced lipid accumulation and ROS generation. Our results suggest that BGN has beneficial effects against muscle atrophy and hepatocellular senescence, indicating its potential as a protective factor for age-related diseases. Full article

Background/Objectives: Obesity is a chronic metabolic disorder characterized by the excessive expansion of adipose tissue and impaired energy homeostasis. Natural products, such as plant extracts, are gaining attention as potential anti-obesity agents. This study aimed to evaluate and compare the anti-obesity effects of ginger (Zingiber officinale Roscoe) extract alone and as a mixture with long pepper (Piper longum L.) extract in a mouse model of high-fat diet-induced obesity. Methods: Male ICR mice were fed a high-fat diet to induce obesity and were orally administered ginger extract (60 mg/kg/day) or a 1:1 mixture of ginger and long pepper extracts (30 mg/kg/day each) for 8 weeks. Body weight, fat mass, glucose tolerance, and serum lipid levels were measured. Results: Ginger extract alone significantly reduced body weight gain and visceral and subcutaneous fat accumulation and improved glucose homeostasis and serum lipid profiles compared to the high-fat diet group. These effects were more pronounced than those observed with the mixture group. Ginger extract upregulated lipolytic markers via activation of the protein kinase A (PKA) signaling pathway and increased expression of uncoupling protein 1 (UCP1), indicating browning of white adipose tissue. Conclusions: Ginger extract alone exhibited significant anti-obesity effects compared to the mixture with long pepper extract. These findings suggest that ginger extract may serve as a promising natural agent for the prevention and management of obesity-related metabolic dysfunction. Full article

Oxidative stress caused by excessive reactive oxygen species (ROS) contributes to numerous chronic diseases. Marine green algae of the Caulerpa genus are rich in bioactive compounds with potential antioxidant activity. Objective: This study aimed to evaluate the intracellular antioxidant effects of caulerpin (CAU) and its derivative caulerpinic acid (CA) using Saccharomyces cerevisiae as a eukaryotic model. Methods: Yeast cells were pretreated with 1 μM of CAU or CA, or with 1 μM of resveratrol (RESV) as a positive control, then exposed to 2 mM of H₂O₂. Growth, ROS levels, oxidative damage markers, and antioxidant defenses were assessed. Results: Both CAU and CA significantly improved cell survival under oxidative stress, restoring growth rates (CAU: 0.129 h⁻¹, CA: 0.137 h⁻¹) and doubling times (CAU: 5.38 h, CA: 5.07 h) close to control values. Intracellular ROS accumulation, protein carbonylation, and lipid peroxidation were reduced to near-baseline levels. While catalase (Cat) and superoxide dismutase (Sod) activity remained unchanged, CAU and CA elevated intracellular glutathione (GSH) levels (1.6–1.8 fold) and preserved glutathione peroxidase (GPx) activity, compared to stressed cells without antioxidant pretreatment. Conclusions: CAU and CA act as effective intracellular antioxidants, primarily via ROS scavenging and GSH-dependent pathways. These findings support their potential as natural candidates for developing antioxidant-based therapies against ROS-related disorders. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline, synaptic loss, and multifaceted pathology involving amyloid-β (Aβ) aggregation, tau hyperphosphorylation, neuroinflammation, and impaired proteostasis. In recent years, biologic therapies, such as monoclonal antibodies, vaccines, antisense oligonucleotides (ASOs), and gene therapies, have gained prominence as promising disease-modifying strategies. In this review, we provide a comprehensive synthesis of current biologic approaches under clinical evaluation for AD. Drawing on data curated from ClinicalTrials.gov (as of 2025), we systematically summarise the molecular targets, therapeutic modalities, mechanisms of action, trial phases, and sponsors of over 60 biologic agents. These include Aβ-directed antibodies targeting distinct conformers such as protofibrils, pyroglutamate-modified species, and soluble oligomers; tau-targeted immunotherapies and RNA-based interventions; and emerging platforms focused on neuroimmune modulation, peptide hormones, and microbiota-based strategies. Gene and RNA therapeutics, particularly ASOs and small interfering RNAs (siRNAs) delivered intrathecally or via lipid nanoparticles, are also reviewed for their potential to modulate intracellular targets with high specificity. We also analyse the historical landscape of biologic candidates that failed to reach approval, discussing key reasons for trial discontinuation, including lack of clinical efficacy, safety concerns (e.g., amyloid-related imaging abnormalities), or inadequate biomarker responses. These cases offer crucial insights for refining future drug design. Looking ahead, we highlight major challenges and evolving perspectives in AD biologic therapy: expanding therapeutic targets beyond Aβ and tau, overcoming delivery barriers to the brain, designing prevention-oriented and genetically stratified trials, and navigating regulatory and ethical considerations. Together, these efforts signal a paradigm shift in AD drug development, from symptomatic treatment to mechanism-based precision biologics. By integrating real-time clinical trial data with mechanistic insight, this review aims to inform both translational research and therapeutic innovation in AD. Full article