Search Results (195)

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

Mitochondrial dysfunction is a key driver of neurological disorders due to the brain’s high energy demands and reliance on mitochondrial homeostasis. Despite advances in genetic characterization, the heterogeneity of mitochondrial diseases complicates diagnosis and treatment. Mitochondrial dysfunction spans a broad clinical spectrum, from early-onset encephalopathies to adult neurodegeneration, with phenotypic and genetic variability necessitating integrated models of mitochondrial neuropathology. Mutations in nuclear or mitochondrial DNA disrupt energy production, induce oxidative stress, impair mitophagy and biogenesis, and lead to neuronal degeneration and apoptosis. This narrative review provides a structured synthesis of current knowledge by classifying mitochondrial-related neurological disorders according to disrupted biochemical pathways, in order to clarify links between genetic mutations, metabolic impairments, and clinical phenotypes. More specifically, a pathway-oriented framework was adopted that organizes disorders based on the primary mitochondrial processes affected: oxidative phosphorylation (OXPHOS), pyruvate metabolism, fatty acid β-oxidation, amino acid metabolism, phospholipid remodeling, multi-system interactions, and neurodegeneration with brain iron accumulation. Genetic, clinical and molecular data were analyzed to elucidate shared and distinct pathophysiological features. A comprehensive table synthesizes genetic causes, inheritance patterns, and neurological manifestations across disorders. This approach offers a conceptual framework that connects molecular findings to clinical practice, supporting more precise diagnostic strategies and the development of targeted therapies. Advances in whole-exome sequencing, pharmacogenomic profiling, mitochondrial gene editing, metabolic reprogramming, and replacement therapy—promise individualized therapeutic approaches, although hurdles including heteroplasmy, tissue specificity, and delivery challenges must be overcome. Ongoing molecular research is essential for translating these advances into improved patient care and quality of life. Full article

Background: The limited bioavailability of free phytosterols restricts their clinical application in managing hypercholesterolemia. This study aimed to develop phytosterol nanoparticles (PNs) to enhance bioactivity and investigate their cholesterol-lowering efficacy and underlying mechanisms in vivo. Methods: Phytosterol nanoparticles (PNs) (93.35 nm) were engineered using soy protein isolate and administered orally at concentrations of 4.00–12.50 mg/mL to high-fat-diet-induced hypercholesterolemic mice (n = 60) over a 4-week period. Serum and hepatic lipid profiles, histopathology, gene/protein expression related to cholesterol metabolism, and fecal sterol content were evaluated. Results: PNs dose-dependently reduced serum total cholesterol (TC: 28.6–36.8%), triglycerides (TG: 22.4–30.1%), and LDL-C (31.2–39.5%), while increasing HDL-C by 18.7–23.4% compared to hyperlipidemic controls (p < 0.01). Hepatic TC and TG accumulation decreased by 34.2% and 41.7%, respectively, at the highest dose, with histopathology confirming attenuated fatty degeneration. Mechanistically, PNs simultaneously suppressed cholesterol synthesis through downregulating HMGCR (3.2-fold) and SREBP2 (2.8-fold), while enhancing cholesterol catabolism via CYP7A1 upregulation (2.1-fold) at protein level. Although less potent than simvastatin (p < 0.05), the nanoparticles exhibited unique dual-pathway modulation absent in conventional phytosterol formulations. Fecal analysis revealed dose-responsive cholesterol excretion (36.01 vs. 11.79 mg/g in controls), indicating enhanced enteric elimination. While slightly less potent than simvastatin (p < 0.05), PNs offered unique dual-pathway modulation absent in conventional phytosterol formulations. Conclusions: Nano-encapsulation significantly improves the bioavailability and hypocholesterolemic efficacy of phytosterols. PNs represent a promising nutraceutical strategy for cholesterol management by concurrently regulating cholesterol synthesis and catabolism, with potential application in both preventive and therapeutic contexts. Full article

Background/Objectives: Degenerative lumbar spinal stenosis (LSS) is a prevalent cause of disability in elderly populations, often treated with decompressive surgery. However, postoperative functional outcomes are variable and influenced by factors beyond neural compression alone. This study aimed to investigate the prognostic significance of the Goutallier Classification System (GS), a radiological index of paravertebral muscle fatty degeneration, in predicting long-term postoperative disability and pain in elderly patients undergoing decompression for LSS. Methods: A retrospective cohort study was conducted on 100 elderly patients who underwent primary lumbar decompression surgery for LSS between January 2020 and July 2022, with a minimum two-year follow-up. Patients were stratified according to their preoperative GS grades assessed via MRI. The Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) for pain were collected preoperatively and at follow-up. Changes in the ODI and VAS (ΔODI and ΔVAS) were analyzed to evaluate associations between GS grades and functional outcomes. Results: Significant improvements in the ODI (from 41.0 ± 17.5 to 16.9 ± 8.2) and VAS (from 6.23 ± 2.52 to 3.75 ± 2.38) were observed postoperatively (p < 0.01). However, higher GS grades were associated with greater residual disability and pain at follow-up, as well as with smaller postoperative improvements in these scores (p < 0.01 for ODI; p = 0.01 for VAS). Gender differences were noted, with females predominating in higher GS grades. No significant differences in comorbidities or complication rates were identified across GS subgroups. Conclusions: Preoperative paravertebral muscle degeneration, as measured by the GS, emerged as a significant predictor of postoperative disability and pain in elderly LSS patients. Incorporating GS assessment into preoperative planning may refine surgical risk stratification and inform shared decision-making to optimize long-term functional recovery. Full article

BYVET JOINT HEAL^TM (BJH) contains mucopolysaccharide protein, chondroitin sulfate, type II collagen, and omega-3 fatty acids, which protect and prevent osteoarthritis (OA)-associated tissue damage and degradation in dogs and cats. This study aimed to generate a novel dietary supplement and evaluate its prevention and therapeutic efficacy in an OA Sprague Dawley rat model induced using monosodium iodoacetate (MIA). Negative control, MIA-induced OA control (MIA), OA rats treated with BJH three weeks after (M+BJH3) and those treated two weeks before and three weeks after OA induction (BJH2+M+BJH3) groups were assigned. M+BJH3 and BJH2+M+BJH3 had similar mean body weight increases until 29 days. BJH2+M+BJH3 showed a significantly higher body weight than M+BJH3 and MIA on the final day. Interleukin-1β in BJH2+M+BJH3 was significantly lower than that in MIA. Tumor necrosis factor-α, aggrecan, matrix metalloproteinases13, and cyclooxygenase-2 levels in M+BJH3 and BJH2+M+BJH3 significantly differed compared to those in MIA. BJH administration before OA induction significantly decreased OA severity and functional recovery. Consuming a BJH supplement showed modifying and chondroprotective effects and significantly reduced cartilage degeneration and inflammation with no side effects. Hence, our findings demonstrate the potential of using BJH as a safe therapeutic and preventive supplement for OA and associated cartilage abnormalities. Also, 30 dogs diagnosed with OA by a veterinarian participated in the clinical trial, and BJH was provided for 8 weeks. Blood tests (CBC, serum chemistry) and joint assessment were performed before and after the feeding, and the effects of a BJH supplement were compared. BJH supplement was easy to administer, and no side effects were reported. Feeding BJH supplementation alone to dogs with arthritis had an overall positive effect on arthritis scores for 8 weeks without any other treatment, including non-steroidal drugs. Full article

Age-related macular degeneration (AMD) is an ocular pathology in humans characterized by the buildup of lipid-rich extracellular deposits, which leads to retinal degeneration. In recent years, considerable effort has been made to observe the effect of dietary fatty acids on oxidative stress and inflammation. In continuation of this, much effort has been made to study the effect of dietary fatty acids on the pathogenesis of AMD. Although studies have shown that dietary fatty acids are effective against few forms of AMD, particularly wet AMD or neovascular AMD, no dietary lipids have shown any conclusive results for dry AMD or geographic AMD. It is therefore important to look for new lipids and lipoproteins that can be helpful in treating various stages of AMD. This article reviews the impact of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) on retinal health and the progression of AMD. Furthermore, this manuscript discusses all studies investigating the implications of fatty acids on AMD, which may be beneficial for future treatment strategies and dietary guidelines related to it. In conclusion, studies suggest that omega-3 PUFAs, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), might provide protection against AMD, highlighting the necessity for additional clinical trials to evaluate their efficacy in the prevention and treatment of AMD. Full article

Background/Objectives: Fatty infiltration of muscle is a predictor of degeneration. The present study determined the effect of an active spinal orthosis on muscle quality as determined by fatty infiltration in paraspinal muscles in older women with vertebral fractures and kyphosis. Methods: Twenty-one community-dwelling women ≥65 years with chronic back pain and vertebral fractures ≥3 months were randomly allocated to a group which wore the Spinomed active orthoses 2 × 2–3 h/d for 16 weeks (SOG: n = 11) or an untreated control group (CG: n = 10). Outcomes of the present study were parameters related to fatty infiltration of the musculi erector spinae and psoas major as determined by Magnetic Resonance Imaging (MRI). We applied a per protocol analysis; data were consistently adjusted for baseline values applying an ANCOVA. Results: Despite positive trends for all MRI parameters, no significant effects of the active spinal orthosis on fat infiltration of the musculus erector spinae were observed. Significant positive effects were, however, determined for musculus psoas major intra-fascial volume (p = 0.021; d’: 1.18) and muscle tissue volume (p = 0.001; d’: 1.80). No further significant effects on m. psoas major intra-fascial or muscle tissue average fat fraction or m. psoas major intramuscular adipose tissue volume were assessed. Of importance, no changes in variables that might have confounded the present result were reported. Conclusions: In line with recent exercise studies, the present high-volume, low-intensity back-strengthening intervention, induced by an active spinal orthosis, failed to generate significant effects on MRI measures of the m. erector spinae. On the other hand, significant effects on m. psoas major hypertrophy, albeit not fatty muscle infiltration, were determined. This new and unexpected finding should be confirmed by future studies. Full article

Neuromuscular disorders (NMDs), such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and muscular dystrophies (e.g., Duchenne muscular dystrophy, DMD), are primarily driven by genetic mutations but are critically modulated by epigenetic mechanisms such as DNA methylation, histone modifications, and noncoding RNA activity. These epigenetic processes contribute to phenotypic variability and disease progression, and emerging evidence suggests that environmental factors, particularly nutrition and exercise, may further influence the molecular pathways that modulate these diseases. Dietary bioactive compounds (e.g., polyphenols and omega-3 fatty acids) exhibit epigenetic modulatory properties, which could mitigate oxidative stress, inflammation, and muscle degeneration in NMDs. For example, the inhibition of DNMTs and HDACs by curcumin in ALS models and the promyogenic effects of green tea catechins in DMD suggest plausible, though still requiring investigation, therapeutic avenues. However, the clinical application of nutriepigenetic interventions is preliminary and requires further validation. This review examines the interaction of genetic and epigenetic factors in ALS, SMA, and muscular dystrophies, highlighting their combined role in the heterogeneity of these diseases. Integrative therapeutic strategies combining gene therapies, epigenetic modulators, and lifestyle interventions may offer a multidimensional approach to the management of NMD. A deeper understanding of these interactions will be essential for advancing precision medicine and improving patient outcomes. Full article

Background/Objectives: Immune cells are integral to bone homeostasis, including the repair and remodeling of bone tissue. Chronic dysregulation within this osteoimmune network can lead to bone marrow defects of the jaw (BMDJ), particularly fatty degenerative osteonecrosis of the jaw (FDOJ). These localized pathologies are implicated in systemic immune dysfunctions. Methods: This study is designed to determine whether BMDJ/FDOJ samples are indicative of medullary bone pathology by evaluating FDOJ gene expression patterns using quantitative real-time PCR. Results: Comparative analyses between pathological and healthy samples evaluated the dysregulation of key molecular pathways. BMDJ/FDOJ samples showed significant upregulation of inflammatory mediators, including CCL5/RANTES, VEGF, IGF and KOR, and downregulation of structural proteins, such as collagen types I, II and IV, and osteogenesis-associated factors, such as SP7. Conclusions: The study provides new insights into the molecular mechanisms of BMDJ/FDOJ by identifying potential molecular changes suggesting a pro-inflammatory state in the affected jawbone which may contribute to systemic immune dysregulation. The findings are consistent with morphologic observations of BMDJ/FDOJ in degenerated jawbone and underscore the need for integrative approaches in dentistry and medicine while highlighting BMDJ/FDOJ as a potential target for therapeutic and preventive strategies against systemic diseases and emphasizing its clinical significance. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, and it is characterized by oxidative stress, lipid dysregulation, and dysfunction of the retinal pigment epithelium (RPE). A hallmark of AMD is the presence of drusen, extracellular deposits rich in lipids, proteins, and cellular debris, which are secreted by the RPE. These deposits impair RPE function, promote chronic inflammation, and accelerate disease progression. Despite advancements in understanding AMD pathogenesis, therapeutic strategies targeting lipid dysregulation and oxidative damage in RPE cells remain limited. This study evaluated the effects of liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on free fatty acid (FFA)-induced damage in ARPE-19 cells, a widely used in vitro model of RPE dysfunction. FFA treatment induced lipid droplet accumulation, oxidative stress, and epithelial–mesenchymal transition (EMT), which are processes implicated in AMD progression. Liraglutide significantly reduced lipid droplet accumulation, mitigated oxidative stress, and suppressed EMT, as demonstrated by high-content imaging, immunocytochemistry, and molecular assays. Mechanistic analyses revealed that liraglutide activates AMP-activated protein kinase (AMPK), enhancing lipophagy and restoring lipid homeostasis. Furthermore, liraglutide influenced exosome secretion, altering paracrine signaling and reducing EMT markers in neighboring cells. These findings underscore liraglutide’s potential to address critical mechanisms underlying AMD pathogenesis, including lipid dysregulation, oxidative stress, and EMT. This study provides foundational evidence supporting the development of GLP-1 receptor agonists as targeted therapies for AMD. Full article

Background: As an innovative approach to deep-sea aquaculture, fish farm vessels offer a dual benefit by alleviating the pressure on offshore fishing resources while providing an additional high-quality protein source. However, the potential impacts of vessel coatings on farmed fish remain poorly understood. Methods: In this study, to investigate the effects of vessel coatings on the large yellow croaker (Larimichthys crocea), we established four experimental groups with coating concentrations at 1-fold, 10-fold, 20-fold, and 80-fold levels. Antioxidant enzyme activities in kidney tissues were measured across all groups, while histological and transcriptome analyses were specifically conducted for the 1-fold and 80-fold concentration groups. Results: Firstly, significant alterations in antioxidant enzyme activity were observed in the 80-fold concentration group. Moreover, histological analysis demonstrated more severe pathological changes in kidney tissue at the higher concentration, including interstitial hemorrhage and tubular epithelial cell fatty degeneration. In addition, we identified 11,902 differentially expressed genes (DEGs) by high-throughput sequencing. KEGG pathway enrichment analysis revealed that the DEGs were predominantly involved in critical biological processes, including endoplasmic reticulum protein processing, oxidative phosphorylation, cytokine–cytokine receptor interactions, cell cycle regulation, DNA replication, and PPAR signaling pathways. Finally, the validation of nine selected DEGs through quantitative real-time PCR (qRT-PCR) showed significant correlation with RNA-Seq data, confirming the reliability of our transcriptome analysis. Conclusions: This study provides preliminary insights into the antioxidant stress response mechanisms of L. crocea to coating exposure and establishes a theoretical foundation for optimizing healthy fish farming practices in aquaculture vessels. Full article

Diabetes mellitus is a chronic metabolic disorder that often leads to hepatic complications, including oxidative stress, inflammation, and structural damage, highlighting the need for effective hepatoprotective agents. Glycyrrhiza glabra (licorice), known for its bioactive compounds with medicinal properties, has gained attention as a potential therapeutic option. This study investigated its hepatoprotective effects in a diabetic rat model. Diabetes was induced using streptozotocin, and animals were divided into four groups: a healthy control, a non-diabetic group treated with Glycyrrhiza glabra extract, an untreated diabetic group, and a diabetic group receiving daily doses of the extract. Liver function was assessed through serum enzyme levels (ALT, AST, and ALP), while oxidative stress markers, including malondialdehyde (MDA) and glutathione (GSH), were analyzed. Histological examination was conducted to evaluate inflammation, fibrosis, and fatty degeneration. Treatment with Glycyrrhiza glabra significantly improved liver function in diabetic rats, as evidenced by lower ALT, AST, and ALP levels compared to untreated diabetic rats (p < 0.05), suggesting hepatocyte protection through its antioxidant and anti-inflammatory properties. Favorable changes in oxidative stress markers were observed, with lower MDA levels indicating reduced lipid peroxidation and higher GSH activity reflecting enhanced antioxidant defense. Histological analysis confirmed these protective effects, showing reduced inflammation, diminished fatty degeneration, and overall structural improvements. These findings highlight the hepatoprotective potential of Glycyrrhiza glabra, suggesting it may be a promising therapeutic agent for managing hepatic complications associated with diabetes mellitus, though further research with larger sample sizes and mechanistic studies is needed for confirmation. Full article

The interplay between gut microbiota and retinal health, known as the gut-–retina axis, has gained increasing attention in recent years. Short-chain fatty acids (SCFAs), metabolites produced by gut microbiota, have been identified as key mediators of gut–retina communication. This systematic review explores the role of SCFAs in retinal health and their potential impact on the development and progression of retinal diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. A literature search was conducted across multiple databases, including PubMed, Google Scholar, and Science Direct, to identify studies published between 2014 and December 2024. Studies were included if they investigated the effects of SCFAs on retinal structure, function, or disease pathogenesis in animal models or human subjects. The review included 10 original articles spanning both preclinical and clinical studies. Evidence suggests that SCFAs play a crucial role in maintaining retinal homeostasis through anti-inflammatory and neuroprotective mechanisms. Dysbiosis of the gut microbiota, leading to altered SCFA production, was associated with increased retinal inflammation, oxidative stress, and vascular dysfunction. Furthermore, reduced SCFA levels were linked to the progression of retinal diseases, such as diabetic retinopathy and age-related macular degeneration. Modulation of gut microbiota and SCFA levels through dietary interventions or probiotics may represent a novel therapeutic strategy for preventing or managing retinal diseases. Further research is needed to elucidate the precise molecular mechanisms underlying SCFA-mediated retinal protection and to evaluate the efficacy of targeted therapies in clinical settings. Full article

Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive degeneration of motor neurons. The gut microbiota, a community of microorganisms in the digestive tract, has recently been implicated in ALS pathogenesis through its influence on neuroinflammation and metabolic pathways. This review explores the potential role of digestive microbiota and its metabolites in ALS progression and investigates therapeutic approaches targeting gut microbiota. Methods: A comprehensive review of the current literature was conducted to assess the relationship between gut microbiota composition, microbial metabolites, and ALS progression in patients. We searched for published reports on microbiota composition, microbial metabolites, and ALS, emphasizing the complex interplay between dysbiosis, neuroinflammation, and systemic metabolism. Special emphasis was placed on studies exploring short-chain fatty acids (SCFAs), bacterial amyloids (curli-like factors), and neurotoxins such as β-methylamino-L-alanine (BMAA). The role of the liver–gut axis was evaluated as well. The potential changes in microbiota would sustain the rationale for therapeutic strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions. Results: ALS patients exhibit gut dysbiosis, characterized by reduced SCFA-producing bacteria and an increase in potentially pathogenic genera. Of note, different studies do not agree on common patterns of microbiota being linked to ALS, supporting the need for further, more extensive studies. Dysbiosis sometimes correlates with systemic inflammation and disrupted liver function, amplifying neuroinflammatory responses. Key microbial metabolites, including SCFAs, bacterial amyloids, and BMAA, may exacerbate motor neuron degeneration by promoting protein misfolding, oxidative stress, and neuroinflammation. Emerging therapeutic strategies, including probiotics and FMT, show potential in restoring microbial balance, although clinical data in ALS patients remain limited. Conclusions: The gut microbiota could modulate neuroinflammation and systemic metabolism in ALS. Microbiota-targeted therapies, such as probiotics and dietary interventions, represent promising avenues for mitigating disease progression. Further research is required to validate these interventions through large-scale, longitudinal studies and to develop personalized microbiota-based treatments tailored to individual ALS phenotypes. Full article

Chronic hyperglycemia is a major driver of neurovascular damage in diabetic retinopathy (DR), a leading cause of preventable blindness in adults. DR progression is often undetected until its advanced stages, with oxidative stress recognized as a primary contributor. In diabetes, oxidative stress disrupts retinal cellular balance, damaging proteins, DNA, and lipids, and triggering photoreceptor degeneration. Pterostilbene (Pter), a polyphenol with antioxidant properties, has demonstrated protective effects in DR animal models and was assessed in a pilot clinical study. DR patients treated with 250 mg/day of oral Pter showed a reduction in the development of retinal vascular alterations characteristic of the disease. Urinary analyses confirmed Pter’s role in reducing the lipid peroxidation of polyunsaturated fatty acids (PUFAs), including arachidonic and adrenic acids, indicators of oxidative damage in DR. Pter also improved the GSH/GSSG ratio, reflecting a restored redox balance. However, after six months without treatment, retinal damage indicators reappeared, highlighting the importance of sustained intervention. These findings suggest that Pter may help slow the progression of DR by protecting against oxidative stress and highlight the importance of implementing antioxidant therapies from the diagnosis of diabetes, although its long-term impact and the development of consistent biomarkers deserve more research to optimize DR management. Full article