Search Results (2,064)

Background and Objectives: The uric acid to HDL-cholesterol ratio (UHR) has recently emerged as a promising biomarker reflecting systemic inflammation and metabolic disturbances. Elevated liver transaminases are clinical indicators of hepatic injury and underlying metabolic dysfunction. Many Middle Eastern countries face constrained clinical and laboratory resources, where access to comprehensive diagnostic tools may be limited. In such settings, identifying simple and easily accessible markers could offer significant practical value in detecting and monitoring health disorders. This study investigates the potential association between UHR and elevated liver transaminases levels in the Saudi general population. Materials and Methods: This retrospective cross-sectional study included 9618 subjects, and the association between the UHR and elevated liver transaminases, alanine transaminase (ALT), and aspartate transaminase (AST), was comprehensively analysed. In addition, the study assessed risk indicators including the prevalence ratio (PR) and odds ratio (OR) as well as the diagnostic accuracy of UHR and C-reactive protein (CRP) in detecting liver transaminases abnormalities, with analyses stratified by age and gender. Results: UHR was significantly elevated in subjects with increased ALT and AST activities, and this pattern was consistent across all age and gender categories. High UHR was significantly associated with elevated ALT (OR = 2.32, 95% CI: 2.12–2.53, p < 0.001) and AST (OR = 1.38, 95% CI: 1.25–1.52, p < 0.001), with stronger associations observed in males and for ALT activity. In addition, elevated UHR was more prevalent among individuals with increased liver transaminase activities. Receiver operating characteristic (ROC) analysis showed that UHR outperformed CRP in identifying elevated liver transaminases, with better discriminative ability for ALT than AST activity. Conclusions: These findings highlight a significant association between UHR and liver transaminase abnormalities in the general population, underscoring the potential utility of UHR as a simple and accessible indicator for liver function assessment in clinical settings. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Understanding the components of the diet, food groups, and nutritional strategies that help prevent MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) is essential for identifying dietary behaviors that can stop the progression of this condition, which currently affects over one-quarter of the global population. This review highlights the importance of including antioxidant nutrients in the diet, such as vitamins C and E, CoQ10, and polyphenolic compounds. It also emphasizes substances that support lipid metabolism, including choline, alpha-lipoic acid, and berberine. Among food groups, it is crucial to choose those that help prevent metabolic disturbances. Among carbohydrate-rich foods, vegetables, fruits, and high-fiber products are recommended. For protein sources, eggs, fish, and white meat are preferred. Among fat sources, plant oils and fatty fish are advised due to their content of omega-3 and omega-6 fatty acids. Various dietary strategies aimed at preventing MASLD should include elements of the Mediterranean diet or be personalized to provide anti-inflammatory compounds and substances that inhibit fat accumulation in liver cells. Other recommended dietary models include the DASH diet, the flexitarian diet, intermittent fasting, and diets that limit fructose and simple sugars. Additionally, supplementing the diet with spirulina or chlorella, berberine, probiotics, or omega-3 fatty acids, as well as drinking several cups of coffee per day, may be beneficial. Full article

Background/Objectives: Rest–activity rhythm (RAR) disturbances can contribute to aging and dementia via metabolic dysregulation. Hydroxycholesterol (OH) is thought to mediate the link between hypercholesterolemia and neurodegeneration. This study compared sleep and RAR parameters between amnestic mild cognitive impairment (aMCI) patients and normal controls (NCs), and examined their associations with plasma 27-OH levels, reflecting peripheral cholesterol metabolism. Methods In total, 18 aMCI patients (76.6 ± 6.1 years) and 21 NCs (70.4 ± 6.7 years) underwent five-day actigraphy and dim light melatonin onset assessment. Plasma 27-OH levels were measured via high-performance liquid chromatography-mass spectrometry. Generalized linear models (GLMs) were used to analyze the relationships between sleep, RAR, and 27-OH levels. Results: The aMCI group had significantly lower 27-OH levels and 27-OH/total cholesterol ratios (p < 0.05). GLM revealed that longer sleep onset latency (SOL) was associated with higher 27-OH levels in aMCI, distinguishing them from NCs. Additionally, in aMCI, longer SOL, lower sleep efficiency (SE), and higher fragmentation index (FI) were associated with an increased 27-OH/total cholesterol ratio (p < 0.05). Higher relative amplitude of RAR was linked to lower 27-OH levels across groups (p < 0.01), but RAR parameters showed no significant association with the 27-OH/total cholesterol ratio. Sleep disturbances, including prolonged SOL, reduced SE, and increased FI, were associated with altered peripheral cholesterol oxygenation in aMCI. Conclusions: Greater RAR amplitude correlated with lower 27-OH levels, regardless of cognitive status. These findings suggest that peripheral cholesterol oxygenation in aMCI is related to both sleep disturbances and circadian rhythm dysregulation, highlighting their role in cholesterol metabolism and neurodegeneration. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder frequently associated with metabolic and inflammatory disturbances. Due to its antioxidant and anti-inflammatory properties, pomegranate juice has been proposed as a potential adjunctive therapy in managing PCOS. To evaluate the effects of pomegranate juice on hormonal, inflammatory, and lipid parameters and body mass index (BMI) in women with PCOS. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. Comprehensive searches were performed in electronic databases including Medline, Scopus, Web of Science, Cochrane CENTRAL, and Embase from inception to July 2025, using keywords and MeSH terms related to “polycystic ovary syndrome” and “pomegranate juice” without language restrictions. The primary outcomes were changes in serum testosterone, luteinizing hormone (LH), high-sensitivity C-reactive protein (hs-CRP), lipid profile parameters (HDL, LDL, triglycerides, and total cholesterol), and body mass index (BMI). Results: Four RCTs published between 2020 and 2023, encompassing 128 women with PCOS, were included. The meta-analysis revealed significant reductions in testosterone (MD: −0.05; 95% CI: −0.07 to −0.03; p < 0.0001; I² = 0%, two studies, 85 participants) and hs-CRP (SMD: −0.85; 95% CI: −1.35 to −0.35; p = 0.0009; I² = 20%, two studies, 85 participants), along with increases in HDL (MD: 6.21; 95% CI: 2.43 to 10.00; p = 0.001; I² = 0%, two studies, 85 participants) and reductions in triglycerides (MD: −23.30; 95% CI: −45.19 to −1.42; p = 0.04; I² = 0%, two studies, 85 participants). No significant changes were observed in LH, LDL, total cholesterol, or BMI. Conclusions: Pomegranate juice demonstrates promising effects as an adjunctive intervention in women with PCOS, improving androgen levels, inflammatory markers, and certain lipid parameters. Further long-term studies are needed to confirm these findings. Full article

Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a serious social problem. Risk factors for the development of these diseases include overweight and obesity, gender, and intestinal microbiome disorders. Another factor that is considered to influence joint diseases is trace elements. Under normal conditions, elements such as iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni) selenium (Se), boron (B), and silicon (Si) are part of enzymes involved in reactions that determine the proper functioning of cells, regulate redox metabolism, and determine the maturation of cells that build joint components. However, when the normal concentration of the above-mentioned elements is disturbed and toxic elements are present, dangerous joint diseases can develop. In this article, we focus on the role of trace elements in joint function. We describe the molecular mechanisms that explain their interaction with chondrocytes, osteocytes, osteoblasts, osteoclasts, and synoviocytes, as well as their proliferation, apoptosis, and extracellular matrix synthesis. We also focus on the role of these trace elements in the pathogenesis of joint diseases: rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). We describe the roles of increased or decreased concentrations of individual elements in the pathogenesis and development of joint diseases and their impact on inflammation and disease progression, referring to molecular mechanisms. We also discuss their potential application in the treatment of joint diseases. Full article

Schistosoma mansoni infection is associated with hepatic inflammation and fibrosis, but its systemic metabolic effects remain poorly understood. This study aimed to investigate changes in the serum lipidomic profile associated with S. mansoni infection and parasite load in individuals from an endemic area. This cross-sectional analysis was nested within a longitudinal cohort study conducted in northeastern Brazil. Parasitological diagnosis and quantification were performed using the Kato–Katz technique. A total of 45 individuals were selected and divided into three groups: high parasite load (HL), low parasite load (LL), and uninfected controls (NegE). Serum samples were analyzed using mass-spectrometry-based lipidomics. The most abundant lipid subclasses across all groups were phosphatidylcholines (PC), triacylglycerols (TAG), and phosphatidylethanolamines (PE). However, individuals in the HL group exhibited distinct lipidomic profiles, with increased levels of specific phosphatidylinositols (PI) and reduced levels of certain TAG species compared to the NegE group. These changes may reflect host–parasite interactions and immune–metabolic alterations driven by intense infection. Our findings suggest that S. mansoni infection, particularly at higher parasite burdens, can influence the host’s serum lipid profile and may contribute to metabolic disturbances in endemic populations. Full article

Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population remain limited. Methods: A single-center, prospective observational study included 100 children aged 4–18 years, with a comparable number of girls and boys. Among them, 72 had IBD (27 CD, 45 UC) and 28 were healthy controls. Anthropometric, biochemical, and densitometric assessments were performed, including serum levels of RANKL and OPG, and markers of inflammation and bone turnover. Results: Children with CD had significantly lower height and weight percentiles compared to UC and controls. Serum RANKL and the RANKL/OPG ratio were significantly elevated in IBD patients, particularly in CD (p < 0.01). Total body BMD Z-scores were lower in IBD compared to controls (p = 0.03). Low BMD was found in 14.7% of UC and 26.3% of CD patients. In both groups, over 30% had values in the “gray zone” (−1.0 to −2.0). A positive correlation was observed between height and weight and bone density (p < 0.01). Higher OPG was associated with lower body weight (p < 0.001), while increased RANKL correlated with osteocalcin (p = 0.03). Patients receiving biological therapy had significantly lower BMD. Conclusions: Pediatric IBD is associated with significant alterations in the RANKL/OPG axis and reduced bone density. These findings support early screening and suggest RANKL/OPG as a potential biomarker of skeletal health. Full article

The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies before and after weight loss. Using mass spectrometry, 275 lipid species were analysed in non-obese controls, patients with severe obesity, and patients one year after bariatric surgery. The results showed that severe obesity disrupts lipid pathways, contributing to lipotoxicity, inflammation, mitochondrial stress, and abnormal lipid metabolism. Although weight loss improved these disturbances, surgery did not fully normalise the lipid profiles of all patients. Outcomes varied depending on their baseline liver health and genetic differences. Persistent alterations in cholesterol handling, membrane composition, and mitochondrial function were observed in partial responders. Elevated levels of sterol lipids, glycerophospholipids, and sphingolipids emerged as markers of complete metabolic recovery, identifying candidates for targeted post-surgical interventions. These findings support the use of lipidomics to personalise obesity treatment and follow-up. Full article

The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain–body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell–cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection. Full article

Hypomagnesemia is a frequent and often underrecognized electrolyte disturbance with important clinical consequences, especially in hospitalized and critically ill patients. This multifactorial condition arises from impaired intestinal absorption, renal magnesium wasting, and the effects of various medications. Magnesium, the second most abundant intracellular cation, is crucial in enzymatic and physiological processes; its deficiency is associated with neuromuscular, cardiovascular, and metabolic complications. This narrative review focuses on the mechanisms and clinical consequences of drug-induced hypomagnesemia, highlighting the major drug classes involved such as diuretics, antibiotics, antineoplastic agents, and immunosuppressants. Management strategies include magnesium supplementation and adjunctive therapies like amiloride and SGLT2 inhibitors to reduce renal magnesium losses. Recognizing and addressing drug-induced hypomagnesemia is essential to improve patient outcomes and prevent long-term complications. Full article

Anthropogenic disturbance alters macro- and microclimatic conditions, often increasing ambient temperatures. These changes can strongly affect insects, particularly those experiencing high thermal stress (i.e., large differences between body and environmental temperature), as prolonged exposure to elevated temperatures can reduce their energetic reserves due to increased metabolic demands and physiological stress. We evaluated thermal stress in 16 insect dragonfly species during two sampling periods (2019 and 2022) in preserved and disturbed sites within a tropical dry forest in western Mexico. Also, we compared energetic condition (lipid and protein content) and thoracic mass for the seven most abundant species between both habitat types. In preserved sites, insects showed higher thermal stress at lower maximum temperatures, which decreased as temperatures increased. Dragonflies in disturbed sites maintained consistent levels of thermal stress across the temperature gradient. Thermal stress was linked to lower lipid and protein content, and individuals from disturbed sites had reduced energy reserves. We also found a weak but consistent positive relationship between mean ambient temperature and protein content. In preserved sites, thoracic mass increased with thermal stress, but only at high mean temperatures. These findings suggest that although species can persist in disturbed environments, their energetic condition may be compromised, potentially affecting their performance and fitness. Preserving suitable habitats is essential for preserving both biodiversity and ecological function. Full article

High-temperature stress has become an important factor that has restricted the aquaculture industry. Huso dauricus is a high-economic-value fish that has faced the threat of thermal stress. Based on this point, our investigation aimed to explore the detailed mechanism of the negative impacts of heat stress on the liver metabolism functions in Huso dauricus. In this study, we set one control group (19 °C) and four high-temperature treatment groups (22 °C, 25 °C, 28 °C, 31 °C) with 40 fish in each group for continuous 53-day heat exposure. Histological analysis, biochemical detection, and transcriptome technology were used to explore the effects of heat stress on the liver structure and functions of juvenile Huso dauricus. It suggested heat-stress-induced obvious liver injury and reactive oxygen species accumulation in Huso dauricus with a time/temperature-dependent manner. Serum total protein, transaminase, and alkaline phosphatase activities showed significant changes under heat stress (p < 0.05). In addition, 6433 differentially expressed genes (DEGs) were identified based on the RNA-seq project. Gene Ontology enrichment analysis showed that various DEGs could be mapped to the lipid-metabolism-related terms. KEGG enrichment and immunohistochemistry analysis showed that ferroptosis and FoxO signaling pathways were significantly enriched (p < 0.05). These results demonstrated that thermal stress induced oxidative stress damage in the liver of juvenile Huso dauricus, which triggered lipid metabolism disorder and hepatocyte ferroptosis to disrupt normal liver functions. In conclusion, chronic thermal stress can cause antioxidant capacity imbalance in the liver of Huso dauricus to mediate the ferroptosis process, which would finally disturb the lipid metabolism homeostasis. In further research, it will be necessary to verify the detailed cellular signaling pathways that are involved in the heat-stress-induced liver function disorder response based on the in vitro experiment, while the multi-organ crosswalk mode under the thermal stress status is also essential for understanding the comprehensive mechanism of heat-stress-mediated negative effects on fish species. Full article

The global obesity epidemic and associated metabolic disorders present urgent public health challenges. This study employed a multi-omics approach (lipidomics, metabolomics, and gut microbiome analysis) to investigate how Bletilla striata polysaccharides (BSPs) and composite polysaccharides modulate liver lipid metabolism and gut microbiota in high-fat diet (HFD)-induced obese mice. HFD elevated hepatic phosphatidylcholines, cholesteryl esters (CEs), and acylcarnitines (CARs), alongside increased cecal choline and trimethylamine. BSP interventions reduced hepatic CEs, free fatty acids (FAs), CARs, and cecal sarcosine while restoring gut microbial diversity. Notably, BSP enriched beneficial genera, including Jeotgalicoccus and Atopostipes, and the network analysis revealed negative correlations between these genera and hepatic triglycerides (TGs), implicating the gut–liver axis in lipid metabolism regulation. These findings elucidate the anti-obesity mechanisms of polysaccharides through gut microbiota remodeling and cross-tissue metabolic interactions, providing a foundation for leveraging plant polysaccharides in developing safer, effective obesity therapies. Full article

Background/Objectives: Pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) is complicated by iron overload and hypomagnesemia, both contributing to immune dysfunction and post-transplant morbidity. The combined impact of these metabolic disturbances on pediatric allo-HSCT outcomes remains unexplored. This study aims to determine whether hypomagnesemia can serve as a prognostic biomarker for delayed immune reconstitution and explores its interplay with iron overload in predicting post-transplant complications and survival outcomes. Methods: A retrospective analysis was conducted on 163 pediatric allo-HSCT recipients. Serum magnesium levels were measured at defined intervals post-transplant, and outcomes were correlated with CD4+ T cell recovery, time to engraftment, incidence of graft-versus-host disease (GVHD), and survival within 12 months. Iron status, including siderosis severity, was evaluated using imaging and laboratory parameters obtained from clinical records. Results: Patients who died within 12 months post-transplant exhibited significantly lower magnesium levels. Hypomagnesemia was associated with delayed CD4+ T cell recovery, prolonged engraftment, and an increased risk of acute GVHD. A strong inverse correlation was observed between magnesium levels and the severity of siderosis. Iron overload appeared to exacerbate magnesium deficiency. Additionally, the coexistence of hypomagnesemia and siderosis significantly increased the risk of immune dysfunction and early mortality. No significant association was found with chronic GVHD. Conclusions: Hypomagnesemia is a significant, early predictor of poor outcomes in pediatric allo-HSCT, particularly in the context of iron overload, underscoring the need for early intervention, including iron chelation and MRI, to improve outcomes. Full article