Metabolic Disorders Research Articles

Efficacy and safety of electroacupuncture for metabolic dysfunction-associated fatty liver disease: a study protocol for a multicentre, randomised, sham acupuncture-controlled, patient-blinded clinical trial

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in the world and carries an increased risk of liver-related events, but no approved medicine. Electroacupuncture has...

Impact of PNPLA3 in Lean Individuals and in Cryptogenic Steatotic Liver Disease.

Although metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity, around 20% of individuals with hepatic steatosis may nonetheless have normal body mass index, a condition often referred to as lean nonalcoholic fatty liver disease (NAFLD). Under the new nomenclature and definition of MASLD, lean NAFLD can be further divided into lean MASLD (when there is one or more cardiometabolic risk factors) and cryptogenic steatotic liver disease (when there is no cardiometabolic risk factor). Current studies suggest that the at-risk PNPLA3 rs738409 variant is more common among individuals with lean NAFLD than their overweight and obese counterparts. However, even in this group, cardiometabolic risk factors are often required for the development of hepatic steatosis and liver injury. In the general population, PNPLA3 gene polymorphism is associated with an increased risk of MASLD, more severe liver histology (i.e., the presence of steatohepatitis and fibrosis) and future development of hepatocellular carcinoma and cirrhotic complications. Emerging data also suggest that individuals carrying the PNPLA3 GG genotype might have a greater reduction in hepatic steatosis and liver enzymes with lifestyle intervention and metabolic treatments, such as glucagon-like peptide-1 receptor agonists. Studies have not specifically examined the impact of PNPLA3 in lean individuals.

Exploring the Nephrotoxicity and Molecular Mechanisms of Di-2-ethylhexyl phthalate: A Comprehensive Review.

Di-2-ethylhexyl phthalate (DEHP), a widely applied plasticizer in various products, can be absorbed into the human body through several channels and accumulate in the lungs, liver, testes, and kidneys, potentially impairing the function of these organs. Recently, the nephrotoxicity of DEHP has received heightened attention. Numerous epidemiologic findings have demonstrated that DEHP exposure may contribute to renal damage, leading to structural and functional abnormalities and exacerbating the progression of kidney disease. Recent research has discovered the mechanisms behind DEHP-induced nephrotoxicity may involve a variety of pathways, including apoptosis, autophagy, ferroptosis, oxidative stress, inflammation, DNA damage, and lipid metabolism disorders. This review discusses the impact of DEHP on kidney function and delves into the molecular mechanisms of nephrotoxicity mediated by DEHP in recent years. In addition, the review examines evidence for the antioxidant and anti-inflammatory capacities of lycopene, green tea polyphenols, and quercetin in ameliorating DEHP-induced renal injury is reviewed, providing a basis for further research.

Harnessing the therapeutic potential of exercise in extracellular vesicle-based therapy in metabolic disease associated cardiovascular complications.

Cardiovascular disease (CVD) is a leading cause of mortality, affecting ∼18 million individuals each year. Obesity and type 2 diabetes mellitus in particular, both chronic metabolic disorders, are risk factors for CVD. The salutary effects of physical activity in preventing and ameliorating CVD have long been acknowledged, as it improves glucose and lipid homeostasis, alongside attenuating oxidative damage, increasing mitochondrial function, and ultimately improving cardiac function. Exercise serves as a catalyst for the secretion of extracellular vesicles (EVs), facilitating inter-tissue communication, by which tissues can deliver important signals from one tissue to another. In recent years, an increasing number of studies have focused on the cargo encapsulated within exercise-derived EVs, as well as the orchestration of inter-tissue crosstalk aimed at modulating metabolism and tissue function in CVDs. The precise mechanisms underpinning the cardioprotective properties of exercise-derived EVs, however, remains only partially elucidated. This review explores novel EV based therapeutic options in CVD and, in particular, EVs derived from models of exercise to alter metabolism and enhance cardiovascular outcomes.

Neuregulin 4 attenuates pancreatic β-cell apoptosis induced by lipotoxicity via activating mTOR-mediated autophagy

ABSTRACT Neuregulin 4 (Nrg4) is a brown fat-enriched endocrine factor that ameliorates lipid metabolism disorders. Autophagy is critical for pancreatic β-cell to counteract lipotoxicity-induced apoptosis. This study aimed at exploring whether Nrg4 attenuates lipotoxicity-induced β-cell apoptosis by regulating autophagy. The mouse pancreatic β-cell line MIN6 was cultured in palmitic acid (PA) with or without Nrg4 administration. Apoptosis rate, together with anti-apoptotic and pro-apoptotic protein levels, was investigated. Autophagic flux and autophagy-related protein levels along with related signaling pathways that regulate autophagy were also evaluated. Results showed that Nrg4 decreased PA-induced MIN6 apoptosis, enhanced anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) expression and reduced pro-apoptotic proteins Bcl-2-associated X protein (Bax) and cleaved-caspase 3 expressions. Autophagy levels in MIN6 also decreased with PA treatment and Nrg4 administration reactivated autophagy. Further, Nrg4 administration activated autophagy via the mammalian target of rapamycin (mTOR) signaling pathway. In addition, when the mTOR pathway was stimulated or autophagy was suppressed, the beneficial effects of Nrg4 administration on MIN6 apoptosis were diminished. These results imply that Nrg4 administration attenuates MIN6 apoptosis by promoting mTOR-dependent autophagy and thus may lead to a new therapeutic method for type 2 diabetes mellitus (T2DM).

A review of multiple diagnostic approaches in the undiagnosed diseases network to identify inherited metabolic diseases.

The number of known inherited metabolic diseases (IMDs) has been expanding, and the rate of diagnosis is improving with the development of innovative approaches including next generation sequencing (NGS). However, a substantial proportion of IMDs remain undetected by traditional diagnostic approaches. We aim to highlight the spectrum of IMDs diagnosed by the Undiagnosed Diseases Network (UDN) and to learn from the UDN diagnostic processes that were able to detect IMDs. We conducted a retrospective analysis of 757 UDN participants diagnosed from 2015 until 2023 using the cohort database, which were divided into a cohort with IMDs (n = 194; 27%) and a cohort whose phenotypes were not explained by an IMD (n = 563; 73%), based on the International Classification of Inherited Metabolic Disorders (ICIMD). Then, we divided the causes of the metabolic 194 diagnoses into seven groups that included all the ICIMD categories. We inspected which clinical and laboratory approaches contributed to a final UDN diagnosis. We also present a UDN case example from each group to highlight the diagnostic yields that resulted from combining newer diagnostic approaches in the UDN and illustrate potential pitfalls of current NGS methods. These 194 cases of IMDs included examples from 21/25 (84%) of the ICIMD categories. Of the UDN subjects 164/194 (85%) were diagnosed with IMDs through NGS. The spectrum of IMDs detected in the UDN cohort is large and growing and appropriate use of newer multiple diagnostic approaches should further increase diagnosis of IMDs that are presently missed by the traditional laboratory screening methods.

Skinny fat model of metabolic syndrome induced by a high-salt/sucrose diet in young male rats.

Childhood and puberty can affect metabolism, leading to tissue injury and malfunction later in life. The consumption of high-processed foods rich in salt and sugar is increasing in middle- and high-income countries, especially among young people. It is necessary to evaluate the effects of high salt and sugar levels in the youth on most injured organs during metabolic challenges. We aimed to investigate whether high salt/sucrose intake affects whole-body development and leads to end-organ injury. Weaned Male Wistar rats were divided into two groups: a control group fed a standard diet (CO) and tap water, and an experimental group (SS) fed a standard diet and a beverage containing 1.8% NaCl and 20% sucrose instead of tap water. The animals were treated for 60 days, starting after weaning at 21 days of age, after which the animals were subjected to glucose and insulin tolerance tests, urine collection, and heart rate monitoring, and euthanized for sample collection at 81 days of age. SS showed reduced body weight gain and increased food intake of sodium/sucrose solution. Interestingly, high salt/sucrose intake led to increased body adiposity, liver lipid inclusion, heart rate, and renal dysfunction. SS exhibits increased levels of peroxisome proliferator-activated receptor alpha to counterbalance the hypertrophy of brown adipose tissue. Our findings reveal that the SS rat model exhibits non-obvious obesity with end-organ damage and preserved brown adipose tissue function. This model closely parallels human conditions with normal BMI but elevated visceral adiposity, providing a relevant tool for studying atypical metabolic disorders.

Effect of vitamin D adjuvant therapy on the proportion of regulatory T cells in peripheral blood and pregnancy outcome of patients with recurrent miscarriage.

Recurrent miscarriage (RM) is influenced by immune factors, particularly regulatory T cells, which can impact immune function and miscarriage risk. Vitamin D (VD) is known to regulate the immune system, potentially improving pregnancy outcomes in RM patients. This study aims to assess the effect of VD adjuvant therapy on regulatory T cells and pregnancy outcomes in RM patients. Clinical data from 104 individuals with RM admitted to our hospital between March 2022 and February 2023 were allocated at random to either the VD group (VDG) or the control group (CG), with 52 patients in each group. Both groups received standard treatment; the CG was treated with aspirin, while the VDG received additional VD therapy. Outcomes measured included regulatory T cell proportion, metabolic factors, immune inflammatory markers, and pregnancy outcomes. After treatment, the proportion of regulatory T cells in VDG was considerably higher (p < 0.05). Additionally, triglyceride levels, leptin, fasting blood glucose, and fasting insulin were lower in the VDG, whereas adiponectin levels were higher (p < 0.05). Levels of progesterone, luteinizing hormone, and 25-hydroxy VD were also higher in the VDG (p < 0.05). Furthermore, interleukin-17, gamma interferon, tumor necrosis factor-α, and C-reactive protein were lower in the VDG (p < 0.05). The pregnancy success rate in the VDG was higher, and the preterm birth rate was lower (p < 0.05). Adjuvant treatment with VD can increase the proportion of regulatory T cells in peripheral blood of individuals with recurrent abortion, regulate metabolic disorder, alleviate immune inflammation, and improve pregnancy outcome.

Targeted TGF-βR2 Silencing in the Retrotrapezoid Nucleus Mitigates Respiratory Dysfunction and Cognitive Decline in a Mouse Model of Cerebral Amyloid Angiopathy with and without Stroke.

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-beta peptides within cerebral blood vessels, leading to neurovascular complications. Ischemic strokes result from acute disruptions in cerebral blood flow, triggering metabolic disturbances and neurodegeneration. Both conditions often co-occur and are associated with respiratory dysfunctions. The retrotrapezoid nucleus (RTN), which is crucial for CO2 sensing and breathing regulation in the brainstem, may play a key role in breathing disorders seen in these conditions. This study aims to investigate the role of Transforming Growth Factor Beta (TGF-β) signaling in the RTN on respiratory and cognitive functions in CAA, both with and without concurrent ischemic stroke.Adult male Tg-SwDI (CAA model) mice and C57BL/6 wild-type controls underwent stereotaxic injections of lentivirus targeting TGF-βR2 in the RTN. Stroke was induced by middle cerebral artery occlusion using a monofilament. Respiratory functions were assessed using whole-body plethysmography, while cognitive functions were evaluated through the Barnes Maze and Novel Object Recognition Test (NORT). Immunohistochemical analysis was conducted to measure TGF-βR2 and GFAP expressions in the RTN.CAA mice exhibited significant respiratory dysfunctions, including reduced respiratory rates and increased apnea frequency, as well as impaired cognitive performance. TGF-βR2 silencing in the RTN improved respiratory functions and cognitive outcomes in CAA mice. In CAA mice with concurrent stroke, TGF-βR2 silencing similarly enhanced respiratory and cognitive functions. Immunohistochemistry confirmed reduced TGF-βR2 and GFAP expressions in the RTN following silencing.Our findings demonstrate that increased TGF-β signaling and gliosis in the RTN contribute to respiratory and cognitive dysfunctions in CAA and CAA with stroke. Targeting TGF-βR2 signaling in the RTN offers a promising therapeutic strategy to mitigate these impairments. This study is the first to report a causal link between brainstem gliosis and both respiratory and cognitive dysfunctions in CAA and stroke models.

Diagnosis and prognosis prediction of gastric cancer by high-performance serum lipidome fingerprints.

Early detection is warranted to improve prognosis of gastric cancer (GC) but remains challenging. Liquid biopsy combined with machine learning will provide new insights into diagnostic strategies of GC. Lipid metabolism reprogramming plays a crucial role in the initiation and development of tumors. Here, we integrated the lipidomics data of three cohorts (n = 944) to develop the lipid metabolic landscape of GC. We further constructed the serum lipid metabolic signature (SLMS) by machine learning, which showed great performance in distinguishing GC patients from healthy donors. Notably, the SLMS also held high efficacy in the diagnosis of early-stage GC. Besides, by performing unsupervised consensus clustering analysis on the lipid metabolic matrix of patients with GC, we generated the gastric cancer prognostic subtypes (GCPSs) with significantly different overall survival. Furthermore, the lipid metabolic disturbance in GC tissues was demonstrated by multi-omics analysis, which showed partially consistent with that in GC serums. Collectively, this study revealed an innovative strategy of liquid biopsy for the diagnosis of GC on the basis of the serum lipid metabolic fingerprints.

Weighted Gene Co-Expression Network Based on Transcriptomics: Unravelling the Differentiation Dynamics of 3T3-L1 Preadipocytes and the Regulatory Mechanism of Protopanaxatriol

The intricate regulatory mechanisms governing adipocyte differentiation are pivotal in elucidating the complex pathophysiology underlying obesity. This study aims to explore the dynamic changes in gene expression during the differentiation of 3T3-L1 adipocytes using transcriptomics methods. Protopanaxatriol (PPT) significantly inhibited adipocyte differentiation. To uncover the molecular mechanisms, we conducted an extensive transcriptomic analysis of adipocytes throughout various differentiation stages, comparing gene expression profiles before and after PPT treatment. The construction of 16 co-expression modules was achieved using weighted gene co-expression network analysis (WGCNA). The 838 differentially expressed genes in the blue module were highly correlated with PPT treatment. Further analysis revealed that PIKfyve, STAT3, JAK1, CTTN, TYK2, JAK3, STAT2, STAT5b, SOCS3, and IRF9 were core genes closely associated with adipocyte differentiation. This discovery underscores the potential pivotal function of these ten genes in regulating adipocyte differentiation. This study elucidated that PPT, an active ingredient in ginseng, could reduce lipid accumulation by inhibiting the differentiation of adipocyte precursors through the negative regulation of genes such as PIKfyve, STAT3, and JAK1. Finally, molecular docking identified potential binding sites for PPT on PIKfyve and JAK1. This study provides potential drug targets for preventing obesity and related metabolic diseases.

Chrna2 Driven CRE is Expressed in Beige Adipocytes.

Significant research interest has been focused on beige adipocytes, activation of which improves glucose and lipid homeostasis, therefore representing new therapeutic opportunities for metabolic diseases. Various Cre/Lox-based strategies have been used to investigate the developmental history of beige adipocytes and how these cells adapt to environmental changes. Despite the significant advancement of our understanding of beige adipocyte biology, much of the molecular insights of the beige adipocyte, including its origin, cell type specific function, remain to be further illustrated. It has previously been shown that Chrna2 (cholinergic receptor nicotinic alpha 2 subunit) has selective functionality in beige adipocytes. In this study, we explore the Chrna2-Cre-driven reporter expression in mouse beige adipocytes in vivo and in vitro. Our findings indicate that Chrna2-Cre expression is present selectively in multiple locular beige adipocytes in subcutaneous inguinal white adipose tissue (iWAT) and differentiated stromal vascular fraction from iWAT. Chrna2-Cre expression was detected in iWAT of young pups and mice after cold exposure where significant number of beige adipocytes are present. Chrna2-Cre driven reporter expression is permanent in iWAT post labeling and can be detected in iWAT of adult mice or mice that have been housed extensively at thermoneutrality after cold exposure, even though only "inactive dormant" beige adipocytes are present in these mice. Chrna2-Cre expression can also be increased by rosiglitazone treatment and β-adrenergic activation. This research, therefore, introduces the Chrna2-Cre line as a valuable tool for tracking the development of beige adipocytes and investigate beige fat function.

Comprehensive analysis of molecular mechanisms underlying kidney stones: gene expression profiles and potential diagnostic markers

BackgroundThe study aimed to investigate the molecular mechanisms underlying kidney stones by analyzing gene expression profiles. They focused on identifying differentially expressed genes (DEGs), performing gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and screening optimal feature genes using various machine learning algorithms.MethodsData from the GSE73680 dataset, comprising normal renal papillary tissues and Randall’s Plaque (RP) tissues, were downloaded from the GEO database. DEGs were identified using the limma R package, followed by GSEA and WGCNA to explore functional modules. Functional enrichment analysis was conducted using KEGG and Disease Ontology. Various machine learning algorithms were used for screening the most suitable feature genes, which were then assessed for their expression and diagnostic significance through Wilcoxon rank-sum tests and ROC curves. GSEA and correlation analysis were performed on optimal feature genes, and immune cell infiltration was assessed using the CIBERSORT algorithm.Results412 DEGs were identified, with 194 downregulated and 218 upregulated genes in kidney stone samples. GSEA revealed enriched pathways related to metabolic processes, immune response, and disease states. WGCNA identified modules correlated with kidney stones, particularly the yellow module. Functional enrichment analysis highlighted pathways involved in metabolism, immune response, and disease pathology. Through machine learning algorithms, KLK1 and MMP10 were identified as optimal feature genes, significantly upregulated in kidney stone samples, with high diagnostic value. GSEA further elucidated their biological functions and pathway associations.ConclusionThe study comprehensively analyzed gene expression profiles to uncover molecular mechanisms underlying kidney stones. KLK1 and MMP10 were identified as potential diagnostic markers and key players in kidney stone progression. Functional enrichment analysis provided insights into their roles in metabolic processes, immune response, and disease pathology. These results contribute significantly to a better understanding of kidney stone pathogenesis and may inform future diagnostic and therapeutic strategies.

The correlation between metabolic dysfunction-associated steatotic liver disease (MASLD) grades and hemodynamic alterations of the portal, hepatic, and splenic vein and spleen size.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver condition worldwide, affecting over 25% of the population. Fatty infiltration in MASLD leads to hemodynamic changes in hepatic circulation, which can be quantitatively assessed using Color Doppler Ultrasonography (US). In this study, we aimed to investigate the correlation of Color Doppler US findings of the portal, hepatic, and splenic venous system within various degrees of MASLD. Between 2021 and 2024, 104 patients referred to Mousavi Hospital at Zanjan University of Medical Sciences were enrolled. Participants were divided into four groups based on the degree of hepatic fatty infiltration on biopsy results: normal, grade 1, grade 2, and grade 3, with 26 subjects in each group (13 men and 13 women). All patients were biopsy proved. Gray-scale and Color Doppler US were used to assess portal and splenic vein peak systolic velocity (PSV), portal and splenic vein diameter, hepatic vein waveform, and spleen size. The Spearman rank correlation was employed to evaluate the relationship between these variables under non-parametric conditions. A significant negative correlation was found between portal vein PSV and MASLD grade (r = - 0.499, p = 0.000). A significant difference was also observed in hepatic venous waveform abnormality between different grades of MASLD (p = 0.043). Accordingly, portal vein PSV and splenic vein PSV had a significantly positive correlation (r = 0.209, p = 0.033). We also observed a positive correlation between the portal vein and splenic diameter (r = 0.210, p = 0.032). Increasing MASLD severity is associated with reduced portal vein PSV and more pronounced abnormalities in hepatic vein flow. Routine assessment of portal and hepatic vein flow using Color Doppler US is recommended to accurately diagnose and monitor the effects of MASLD on hepatic circulation, potentially improving disease management and patient outcomes.

NAFLD No More: A Review of Current Guidelines in the Diagnosis and Evaluation of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Provide a concise update on metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as a practical approach to screening and initial evaluation. Nomenclature changes have placed a greater focus on cardiometabolic risk factors in the definition of MASLD. Screening for MASLD is by stepwise noninvasive serum and imaging tests which can identify patients at risk for advanced fibrosis and liver-related complications. MASLD has been increasing in prevalence and disease burden but is underrecognized in primary care and endocrinology clinics. Multiple society guidelines, synthesized here, provide a framework for the initial approach in the diagnosis and evaluation of MASLD. Recent advances in pharmacologic treatment underline the importance of screening for patients who are at risk for advanced fibrosis as they are most likely to benefit from new drug classes, such as the liver-directed thyroid receptor agonist resmiterom.

Metabolic dysfunction-associated steatotic liver disease: a key factor in hepatocellular carcinoma therapy response

The conceptual evolution of non-alcoholic fatty liver disease (NAFLD) to what, since 2023, is called metabolic dysfunction-associated steatotic liver disease (MASLD) not only represents a change in the classification and definition of the disease but also reflects a broader understanding of this heterogeneous condition, which still with many aspects to refine. Although the definition of NAFLD can be interchanged to a high percentage with the new MASLD concept in different aspects, MASLD has been proposed as a relevant factor that influences the response to new immunotherapeutic treatments in the management of MASLD-related hepatocellular carcinoma (HCC), compared to HCC of other etiologies. This indicates that the etiology of HCC plays a relevant role in the prognosis, highlighting the urgency of evaluating treatment regimens for this subgroup of patients in upcoming clinical trials. A better understanding of the pathophysiology of MASLD generates strategies that not only aid in its management but also provide strategies to directly intervene in the carcinogenesis of HCC.

Non-invasive testing in metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease, affecting up to 30% of the global population. MASLD is strongly associated with metabolic risk factors such as obesity and type 2 diabetes, and can progress to advanced stages including cirrhosis and hepatocellular carcinoma. Early diagnosis and accurate staging of fibrosis are critical in managing the disease and preventing complications. While liver biopsy has long been considered the gold standard for assessing fibrosis, it is invasive and carries associated risks. In response, non-invasive tests (NITs) have emerged as essential alternatives for the diagnosis and monitoring of MASLD. Key methods include blood-based biomarkers such as the Fibrosis-4 (FIB-4) score, NAFLD Fibrosis Score (NFS), and Enhanced Liver Fibrosis (ELF) test, as well as imaging modalities like vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE). These tests provide safer, more accessible methods for identifying liver fibrosis and guiding clinical management. They are integral in assessing disease severity, guiding treatment decisions, and monitoring disease progression, particularly in light of emerging therapies. NITs have become increasingly recommended by clinical guidelines as they reduce the need for invasive procedures like liver biopsy, improving patient care and outcomes. In conclusion, non-invasive testing plays a crucial role in the effective management of MASLD, offering reliable alternatives for diagnosis and monitoring while minimizing risks associated with traditional invasive methods.

COMPLEX PHYSICAL THERAPY OF PATIENTS WITH ADHESIVE CAPSULITIS

Adhesive capsulitis is predominantly an idiopathic condition and is more common in patients with metabolic disorders. PS contracture can be of varying degrees of severity, depending on the pathology of the PS with which we are dealing. This condition greatly aff ects work capacity and quality of life due to the presence of pain, discomfort and limitation of daily life activities. Prolonged pain syndrome can provoke sleep disorders and depression. Disruption of normal sleep, pain and depression form a pathological closed circle and contribute to the maintenance of the pathological process in the locus morbi.The development of a comprehensive program of physical therapy for patients with adhesive capsulitis with the use of modern means of recovery, which will reduce the risk of the disease re-emerging, and will also contribute to the faster recovery of the functional capacity of the musculoskeletal system of the patients.The objective of the study. The develop and practically substantiate a comprehensive program of therapy for patients with adhesive capsulitis using physical therapy.Materials and Research Methods. The study is based on a comprehensive therapeutic approach for 36 patients diagnosed with adhesive capsulitis in the acute phase of the condition. The assessed parameters included X-ray and computed tomography results, evaluation of range of motion in the shoulder joint, joint- muscle apparatus, and analysis of pain intensity indicators.Conclusions. To improve the condition of patients and optimize the process of treatment and rehabilitation of patients with adhesive capsulitis of the shoulder joint in the acute period, it is advisable to use with the diff erentiation of means of therapeutic intervention according to the diagnosis of the international classifi cation of functioning, optimization of physiotherapeutic means and special means of physical therapy allowed to shorten the terms of treatment and recovery of patients with adhesive capsulitis. It was determined that the best combination of means of therapeutic intervention for patients with adhesive capsulitis is the use of a complex of ideomotor exercises to create the patient’s idea of correct movement; correct positioning of the limb during sleep, everyday and professional activity; passive exercises to increase the volume of painless movements (bending, external rotation); restorationof the pattern of typical motor actions and optimization of physiotherapeutic means due to the use of shock wave and TENS therapy signifi cantly improved the eff ectiveness of their recovery in the short-term and long-term stages of the acute period of rehabilitation.

Metabolomic Analysis and Biochemical Profiling of Cadmium-Induced Metabolic Impairment and Its Amelioration by Resveratrol

Exposure to heavy metals, particularly cadmium (Cd), poses significant health risks because of their toxic effects and potential for bioaccumulation in living organisms. This study examined the biochemical and metabolomic changes induced by Cd exposure in an animal model via advanced liquid chromatography with tandem mass spectrometry (LC-MS/MS) and biochemical assays to reveal significant disruptions in lipid and amino acid metabolism as well as alterations in key metabolic pathways. Cd exposure led to significant weight loss, hyperglycemia, and insulin resistance, indicating its role in metabolic disorders such as diabetes. The accumulation of Cd in the liver and kidneys, identified via ICP-OES, corresponded with elevated levels of liver (ALT, AST) and kidney (BUN, creatinine) biomarkers, suggesting organ-specific toxicity. At the metabolic level, Cd exposure caused the accumulation of lipid metabolites such as ceramides and sphingolipids, which are associated with insulin resistance and broader metabolic impairments. Amino acid metabolism was also significantly disrupted, with increased concentrations of key amino acids such as phenylalanine, tryptophan, and arginine affecting pathways such as the urea cycle and Krebs cycle. These metabolic disturbances are linked to oxidative stress, systemic inflammation, and impaired glucose regulation, as evidenced by elevated CRP and IL-6 levels. The protective effects of resveratrol (RSV) were clearly demonstrated in this study. RSV treatment ameliorated Cd-induced biochemical and metabolic alterations, as shown by improved glycemic control, restored lipid profiles, and normalized amino acid concentrations. Additionally, RSV significantly reduced inflammatory markers and improved liver and kidney function, highlighting its antioxidant properties and potential as a therapeutic agent against Cd toxicity. However, RSV did not significantly reduce Cd accumulation in organs, indicating that its protective effects are related to mitigating oxidative damage and metabolic disruption rather than promoting Cd excretion. This study enhances our understanding of the molecular mechanisms underlying Cd-induced metabolic impairments and highlights the therapeutic potential of RSV in combating Cd toxicity. These findings underscore the need for further research into heavy metal exposure and its mitigation to protect human health, particularly in areas of environmental contamination.

Friend or foe: the paradoxical roles of MG53 in diabetes mellitus.

MG53 is predominantly expressed in striated muscles. The role of MG53 in diabetes mellitus has been gradually elucidated but is still full of controversy. Some reports have indicated that MG53 is upregulated in animal models with metabolic disorders, and that muscle-specific MG53 upregulation is sufficient to induce whole-body insulin resistance and metabolic syndrome through targeting both the insulin receptor (IR) and IR substrate-1 (IRS-1) for ubiquitin-dependent degradation. Additionally, MG53 has been identified as a myokine/cardiokine that is secreted from striated muscles into the bloodstream and circulating MG53 has further been shown to trigger insulin resistance by binding to the extracellular domain of the IR, thereby allosterically inhibiting insulin signaling. Conversely, other studies have reported findings that contradict these results. Specifically, no significant change in MG53 expression in striated muscles or serum has been observed in diabetic models, and the MG53-mediated degradation of IRS-1 may be insufficient to induce insulin resistance due to the compensatory roles of other IRS subtypes. Furthermore, sustained elevation of MG53 levels in serum or systemic administration of recombinant human MG53 (rhMG53) has shown no impact on metabolic function. In this review, we will fully characterize these two disparate views, strive to provide critical insights into their contrasts and propose several specific experimental approaches that may yield additional evidence. Our goal is to encourage the scientific community to elucidate the effects of MG53 on metabolic diseases and the molecular mechanisms involved, thereby providing the theoretical basis for the treatment of metabolic diseases and the applications of rhMG53.