Search Results (878)

Parkinson’s Disease (PD) is the fastest-growing neurological disorder, characterized by the degeneration of dopaminergic neurons. Treatments remain symptomatic, and objective biomarkers for therapeutic response are lacking. This review aims to evaluate the potential of Proton Magnetic Resonance Spectroscopy (¹H-MRS) to provide objective and reproducible biomarkers for monitoring treatment response in PD. This systematic review followed PRISMA guidelines. Articles were searched in PubMed, Web of Science, Scopus, and Embase, and studies employing ¹H-MRS to evaluate pharmacological treatments in PD were included, analyzing pre- and post-treatment changes. Six studies were included, investigating cannabinoids, dopamine agonists, monoamine oxidase B inhibitors, and levodopa. Key metabolites analyzed were N-acetylaspartate, Creatine, Choline, myo-Inositol, and Glx (glutamate+glutamine). Increases in NAA, a marker of neuronal integrity and mitochondrial function, suggested neuroprotective mechanisms of dopaminergic drugs, while stable Cho and mI levels, markers of membrane metabolism and inflammatory processes, suggested limited short-term responsiveness. This is the first systematic review evaluating ¹H-MRS for monitoring neurometabolic changes induced by pharmacological treatments in PD. Observed metabolite changes appear to reflect treatment mechanisms and potential neuroprotective properties. Findings suggest that ¹H-MRS may serve as an objective biomarker for assessing therapeutic efficacy and potential neuroprotective drug effects, although further studies are needed to confirm its clinical utility. Full article

The gut microbiome is strongly implicated in the development of obesity and type 2 diabetes mellitus (T2DM). A recent study demonstrated that 6-week oral supplementation of Anaerostipes rhamnosivorans (ARHAM) combined with the prebiotic myo-inositol (MI) reduced fasting glucose levels in mice. In the present study, we investigated the effects of a 13-week ARHAM-MI supplementation in high-fat diet-fed mice and examined the metabolic fate of MI, including its microbial conversion into short-chain fatty acids (SCFAs), using ¹³C-MI and stable isotope tracers in the cecum, portal vein, and peripheral blood. The results showed that the ARHAM-MI group gained less weight than the MI-only and placebo groups. Analysis of intestinal mRNA and stable isotope tracing revealed that MI is primarily absorbed in the upper gastrointestinal tract, whereas microbial conversion to SCFAs predominantly occurs in the cecum and is enhanced by ARHAM. ARHAM-MI mice also showed increased cecal Gpr43 mRNA expression, indicating enhanced SCFA-mediated signaling. Notably, SCFAs derived from MI displayed distinct distribution patterns: ¹³C-butyrate was detected exclusively in the cecum, ¹³C-propionate was present in the cecum and portal vein, whereas ¹³C-acetate was the only SCFA detected in peripheral blood. Collectively, ARHAM-MI co-supplementation confers modest metabolic benefits in high-fat diet-fed mice, underscoring the need to optimize the dosage and administration frequency of ARHAM-MI to enhance its therapeutic efficacy. Full article

This study aimed to evaluate the regenerative effects of various microcurrent waveforms in cast-induced gastrocnemius muscle atrophy in rabbits, integrating both in vitro and in vivo analyses. After two weeks of enforced hindlimb immobilization via casting, twenty-four rabbits were divided into four groups and treated for two weeks: Group-1 (control) received sham microcurrent, Group-2 was treated with a square waveform microcurrent, Group-3 with a sine waveform, and Group-4 with a triangular waveform. Treatments were administered daily for one hour. Calf circumference, muscle thickness (via ultrasound), tibial nerve CMAP, muscle fiber CSA, and protein expression (via Western blot analysis) were assessed. Among the groups, the sine waveform microcurrent resulted in significantly enhanced recovery across all measured parameters (p < 0.05), showing superior improvements in muscle thickness, CMAP amplitude, and fiber CSA. Immunohistochemical analysis revealed increased expression of proliferation and angiogenesis markers, including BrdU, PCNA, VEGF, and PECAM-1, while Western blotting demonstrated robust upregulation of myogenic regulatory factors such as MyoD and myogenin. Furthermore, levels of inflammatory and apoptotic markers, including TNF-α, NF-κB, and cleaved caspase-3, and stress response proteins, including p-CHK1 and p-CHK2, were markedly reduced. Collectively, these findings indicate that sine waveform microcurrent stimulation most effectively promotes muscle regeneration in both dexamethasone-induced C2C12 myoblasts and cast-induced muscle atrophy, underscoring its therapeutic potential and warranting further studies to optimize clinical application parameters. Full article

We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor (RXR), promotes the differentiation and fusion of skeletal myoblasts. We have also analyzed the genomic programs underlying rexinoid-enhanced myogenic differentiation to identify novel regulatory pathways. As such, we observed a significant upregulation of a transcript encoding a predicted transmembrane protein, Tmem182, during C2C12 myoblast differentiation. Despite the documentation of Tmem182 expression in skeletal muscles, its regulation had yet to be explored. Here, we show that Tmem182 gene expression is markedly augmented in early myoblast differentiation and further enhanced by RXR signaling. In addition, Tmem182 expression is specific to muscle tissues and related to muscle master regulator MyoD. We found that MyoD and histone acetyltransferase p300 are bound to the Tmem182 promoter, and Tmem182 expression is p300-dependent. Thus, our data display a putative epigenetic signature associated with p300 and histone acetylation in rexinoid-responsive locus activation and transcription of myogenic targets. Full article

Background/Objectives: Thyroid disorders such as Hashimoto’s thyroiditis and Graves’ disease represent major endocrine challenges worldwide, often requiring long-term management. Recently, nutritional supplementation with selenium and myo-inositol has been proposed as a supportive strategy. This review aims to summarize the current evidence regarding their efficacy in improving thyroid function, reducing thyroid autoantibodies in Hashimoto’s disease, and restoring biochemical euthyroidism in Graves’ disease. Methods: A narrative review of the available literature was undertaken, concentrating on randomized controlled trials and observational studies evaluating selenium and myo-inositol, alone or in combination (MYO+Se), in patients with autoimmune thyroid disorders and benign thyroid nodules. Search Strategy and Study Selection: We searched MEDLINE/PubMed, Embase, Cochrane CENTRAL, and Scopus from inception to 31 July 2025. The search used Boolean operators to combine the following keywords: (“selenium” OR “selenomethionine”) AND (“myo-inositol” OR “inositol”) AND (thyroid OR Hashimoto* OR Graves’ OR hyperthyroid* OR hypothyroid* OR nodule* OR goiter OR orbitopathy). We included human studies in English. Inclusion criteria: Research designs include RCTs, quasi-experimental studies, cohort/case-control studies, and big case series (n ≥ 30). Exclusion criteria: Animal-only or in vitro studies (unless mechanistic), pediatric case reports, and editorials/commentaries. Study selection and data extraction: Two reviewers screened independently; discrepancies were settled through consensus. The data retrieved included the population, baseline iodine/selenium status (if reported), dose/formulation, treatment duration, outcomes (TSH, FT4, FT3, TPOAb, TgAb, TRAb, nodule metrics), and adverse events. Quality assessment: The risk of bias was assessed using the RoB-2 for RCTs and the Newcastle-Ottawa Scale or JBI checklists for observational studies. A qualitative synthesis emphasized study quality, consistency, directness, and accuracy. Results: Clinical research indicate that selenium supplementation may reduce thyroid peroxidase antibody (TPOAb) levels in Hashimoto’s disease, thereby attenuating autoimmune activity. Myo-inositol, particularly when combined with selenium, has been proven to improve thyroid hormone profiles while also lowering nodule size or growth. In Graves’ disease, supplementation has been linked to the restoration of biochemical euthyroidism in certain patients, albeit data are limited. Despite these encouraging results, diversity in trial design, treatment length, and dosages restrict the robustness of existing recommendations. Conclusions: Selenium and myo-inositol supplementation have shown promise as adjuvant treatments for autoimmune thyroid diseases and benign thyroid nodules. However, further large-scale, well-designed clinical trials are needed to determine the appropriate dosages, treatment duration, and patient selection criteria. Personalized supplementation solutions may improve medication efficacy and help with more comprehensive thyroid disease care. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated neurodegenerative disorder marked by inflammation, demyelination, and neuronal loss within the central nervous system. Despite advances in diagnostics, current tools remain insufficiently sensitive and specific. Metabolomics has emerged as a promising approach to explore MS pathophysiology and discover novel biomarkers. This PRISMA-guided systematic review included 29 original studies using validated metabolomic techniques in adult patients with MS. Biological samples analyzed included serum, cerebrospinal fluid, and feces. Consistent metabolic alterations were identified across several pathways. The kynurenine pathway demonstrated a shift toward neurotoxic metabolites, alongside reductions in microbial-derived indoles, indicating inflammation and gut dysbiosis. Energy metabolism was impaired, with changes in glycolysis, tricarboxylic acid (TCA) cycle, and mitochondrial function. Lipid metabolism showed widespread dysregulation involving phospholipids, sphingolipids, endocannabinoids, and polyunsaturated fatty acids, some modulated by treatments such as ocrelizumab and interferon-β. Nitrogen metabolism was also affected, including amino acids, peptides, and nucleotides. Non-classical and xenobiotic metabolites, such as myo-inositol, further reflected host–microbiome–environment interactions. Several studies demonstrated the potential of metabolomics-based machine learning to distinguish MS subtypes. These findings highlight the value of metabolomics for biomarker discovery and support its integration into personalized therapeutic strategies in MS. Full article

Duck enteritis virus (DEV) is responsible for duck viral enteritis, a contagious and lethal disease in waterfowls. The host proteins targeted by DEV are unknown. In this study, we developed a recombinant DEV rVP26-Flag and identified 17 host proteins that interact with VP26 in infected chicken embryo fibroblast cells using co-immunoprecipitation in conjunction with liquid chromatography–tandem mass spectrometry (Co-IP-MS/MS). The 17 potential targets of VP26 proteins include Xirp1, TMOD3, DCN, ATP5PD, AP3M1, MYO5A, MYH10, MYH9 (non-muscle myosin IIA heavy chain), and GSN. Most of these proteins are microfilament or cytoskeletal proteins with functions such as cytoskeletal protein binding, actin filament interaction, microfilament motor activity, and myosin II interaction. Using the Search Tool for the Retrieval of Interacting Genes analysis, we predicted a functional network of microfilament cytoskeletal proteins interacting with VP26. Interaction between DEV VP26 and the carboxyl-terminus domain of MYH9 (1651–1960 aa) was verified via co-localization and Co-IP assays. We also demonstrated that the inhibition of actin polymerization with cytochalasin D and latrunculin A reduced the DEV titer. Furthermore, siRNA-mediated knockdown of MYH9, which has intrinsic ATPase activity, also resulted in a reduced viral titer. A targeted inhibitor of myosin II ATPase, (-)-Blebbistatin, significantly suppressed DEV infection both in vitro and in vivo. These results suggest that the actin–myosin II network plays a crucial role in DEV proliferation, with MYH9 being an important host factor influencing DEV infection. Full article

Myo-inositol oxygenase (MIOX), as the sole enzyme catalyzing myo-inositol (MI) catabolism in mammals, plays a central role in maintaining intracellular MI homeostasis. Dysregulation of MIOX activity disrupts MI metabolic balance, leading to pathological processes including oxidative stress, inflammation, and ferroptosis, which subsequently induce multiple diseases such as metabolic syndrome, neurological disorders, tumors, and reproductive/developmental disorders. This article systematically reviews the structure and function of MIOX as well as the pathological consequences arising from its dysregulation. Although its pathological significance is increasingly recognized, the molecular mechanisms of MIOX in many diseases have not been fully elucidated, and targeted modulators of MIOX are lacking. Future research should focus on the in-depth elucidation of the pathogenic mechanisms of MIOX disorders and the development of MIOX modulators, thereby providing precise therapeutic strategies for related diseases. Full article

This study investigated the role of molecular mimicry in the context of autoimmunity associated with viral infection, using SARS-CoV-2 as a model system. A bioinformatic analysis was performed to identify sequence homologies between the SARS-CoV-2 Spike (S) protein and the human proteome, with a specific focus on immunogenic regions to assess potential cross-reactivity. The analysis revealed homologous regions between the viral S protein and several human proteins, including DAAM2, CHL1, HAVR2/TIM3, FSTL1, FHOD3, MYO18A, EMILIN3, LAMP1, and αENaC, which are predicted to be recognizable by B-cell receptors. Such recognition could potentially lead to the production of autoreactive antibodies, which can contribute to the development of autoimmune diseases. Furthermore, the study examined potential autoreactive CD4+ T-cell responses to human protein autoepitopes that could be presented by HLA class II molecules. Several HLA class II genetic variants were computationally associated with a higher likelihood of cross-reactive immune reactions following COVID-19, including HLA-DPA1*01:03/DPB1*02:01, HLA-DPA1*02:01/DPB1*01:01, HLA-DPA1*02:01/DPB1*05:01, HLA-DPA1*02:01/DPB1*14:01, HLA-DQA1*01:02/DQB1*06:02, HLA-DRB1*04:01, HLA-DRB1*04:05, HLA-DRB1*07:01, and HLA-DRB1*15:01. Additionally, seven T helper cell autoepitopes (YSEILDKYFKNFDNG, ERTRFQTLLNELDRS, AERTRFQTLLNELDR, RERKVEAEVQAIQEQ, NAINIGLTVLPPPRT, PQSAVYSTGSNGILL, TIRIGIYIGAGICAG) were identified that could be implicated in autoimmune T-cell responses through presentation by class II HLA molecules. These findings highlight the utility of viral B- and T-cell epitope prediction for investigating molecular mimicry as a possible mechanism in virus-associated autoimmunity. Full article

To evaluate the effects of dietary threonine levels on rice field eels (Monopterus albus), six experimental diets were formulated with graded threonine supplementation: 0 g/kg (T1), 3 g/kg (T2), 6 g/kg (T3), 9 g/kg (T4), 12 g/kg (T5), and 15 g/kg (T6). Rice field eels, with an initial body weight of 18.47 ± 0.11 g, were fed for 60 days. The weight gain ratio (WGR), specific growth rate (SGR), and protein efficiency ratio (PER) significantly increased in the T4 group, while feed conversion ratio (FCR) significantly decreased. Broken-line regression analysis determined the optimal dietary threonine requirement to be 7.5–9.0 g/kg. Concomitantly, whole-body crude protein content increased, while lipid content decreased; serum GOT and GPT activities declined, indicating reduced hepatic stress, whereas hepatic CAT and SOD activities markedly increased, enhancing antioxidant capacity. Digestive enzyme capacity was enhanced, as evidenced by elevated lipase and trypsin activities. Muscle texture properties, including cohesiveness, springiness, and chewiness, were significantly improved in the T4 and T5 groups. At the molecular level, MyoG, MyoD1, and MYF5 expression peaked in T4, while MRF4 expression increased progressively. LEfSe analysis of the microbiome, coupled with KEGG functional prediction, revealed that Corynebacterium and Methylocella were positively correlated with growth metrics; these genera likely promote muscle deposition through three enriched metabolic pathways that enhance energy and amino acid availability. Collectively, dietary threonine supplementation at 7.5–9.0 g/kg promotes growth, enhances digestive function, and improves muscle quality in rice field eels. Full article

Background: Salmonella Kentucky comprises two major lineages, ST152 and fluoroquinolone-resistant (Flu^R) ST198, which have diverged genotypically and phenotypically along distinct evolutionary and epidemiological trajectories. ST198 is linked to global human disease, while ST152 is primarily animal-associated in the U.S. We hypothesized that lineage-specific metabolic adaptations contribute to their differing host associations and pathogenicity. Methods: We performed comparative metabolic profiling of ST198 (n = 3) and ST152 (n = 4) strains across 948 substrates and environmental conditions. Growth assays tested the ability of these lineages and other non-typhoidal Salmonella (NTS) serovars (n = 5) to utilize myo-inositol and lactulose as sole carbon sources. Comparative genomic analyses of 294 ST198, 173 ST152, and 1300 other NTS serovars identified nutrient utilization genes. Results: ST198 exhibited significantly higher respiratory activity and broader metabolic versatility across carbon, nitrogen/sulfur sources, and stress conditions. The canonical iol gene cluster for myo-inositol catabolism was conserved in ST198 but absent in ST152, which nonetheless showed weak growth on myo-inositol, suggesting an alternative metabolic pathway for myo-inositol may exist. We also report for the first time that, despite lineage-specific differences in metabolic efficiency, multiple NTS serovars, including S. Kentucky, can metabolize lactulose, a synthetic disaccharide traditionally associated with beneficial gut microbes. These results suggest the potential existence of a novel lactulose metabolic pathway in NTS. Conclusions: These findings highlight ST198’s metabolic adaptability and reveal novel metabolic capacities in NTS. A mechanistic understanding of nutrient utilization pathways, particularly of myo-inositol and lactulose, will provide novel insights into the mechanisms underlying nutrient metabolism that likely modulate the ecological success and pathogenic potential of NTS in human and animal hosts. Full article

The study assesses the relationship between thalamic proton-MR spectroscopy (¹H-MRS) metabolites and thalamic ¹¹C-ER176 translocator-protein positron emission tomography (TSPO-PET) standardized uptake value ratios (SUVR) to advance our understanding of thalamic involvement in multiple sclerosis (MS)-associated neurodegeneration and disability. In this prospective cross-sectional study, patients with MS (pwMS) and controls underwent 3T-MRI, ¹H-MRS, and ¹¹C-ER176-PET targeting the thalamus. MRI-derived thalamic volume was normalized by intracranial volume. ¹H-MRS metabolites—N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln), total choline (tCho), and myo-inositol (mIns)—were normalized to total creatine (tCr). Clinical disability was evaluated using MS-specific tests of Expanded Disability Status Scale-EDSS and MS-functional composite-MSFC (including Paced Auditory Serial Addition Test-PASAT). Compared to controls (n = 30), pwMS (n = 21) exhibited smaller thalamic volume, higher thalamic ¹H-MRS mIns/tCr (putative gliosis marker), and higher thalamic ¹¹C-ER176-PET SUVR (glial density marker). In pwMS, higher thalamic mIns/tCr (r = −0.67) and tCho/tCr (r = −0.52) correlated with smaller thalamic volume. In pwMS, higher thalamic mIns/tCr correlated with higher thalamic ¹¹C-ER176-PET SUVR (r = 0.48) and decreased cognitive function (PASAT, rho = −0.48). In controls, decreased thalamic NAA/tCr correlated with increased thalamic ¹¹C-ER176-PET SUVR (r = −0.41). Thalamus, a core central nervous system relay, is affected early in MS disease course. Glial-mediated innate immune activation in the thalamus, evaluated by increased ¹H-MRS mIns/tCr and ¹¹C-ER176-PET SUVR, is associated with loss of thalamic volume and increased disability in pwMS. The multimodal imaging approach with ¹H-MRS mIns/tCr and ¹¹C-ER176-PET SUVR emerges as potential glial biomarkers, to better understand disease mechanisms and evaluate therapeutic interventions targeting glial activity in MS. Full article

Background: Vulvar leiomyosarcoma (VLMS) is a rare and aggressive soft tissue malignancy arising from smooth muscle cells, comprising less than 3% of vulvar cancers. Its clinical resemblance to benign vulvar lesions often leads to delayed diagnosis. Despite surgical resection and adjuvant therapy, VLMS is associated with high recurrence rates and a poor prognosis, and due to its rarity, there is no standardized management or surveillance protocol. Case Report: We present a case of high-grade VLMS in a postmenopausal woman, initially diagnosed in 2020 and managed with surgical excision and adjuvant radiotherapy. The primary tumor was a 10 cm solid, lobulated mass involving the mons pubis, with histology confirming high-grade leiomyosarcoma based on marked cellular atypia, high mitotic activity, and smooth muscle differentiation. Immunohistochemistry was positive for SMA, vimentin, and CD34, and negative for S100 and MyoD1. Five years later, the patient developed a local recurrence with an enlarged inguinal lymph node. She underwent complete tumor resection and bilateral inguinal lymphadenectomy. Histology of the recurrent lesion mirrored the initial findings, with no lymph node metastases. This case highlights the aggressive nature and potential for late recurrence in vulvar leiomyosarcoma, underscoring the importance of long-term surveillance. Conclusions: High-grade VLMS is a rare malignancy with a high recurrence risk. This case highlights the importance of early diagnosis, radical surgical treatment, and long-term surveillance. Although recurrence occurred five years after the initial treatment, timely surgical intervention led to a favorable postoperative course. Multidisciplinary management and individualized follow-up strategies remain key to improving outcomes in these rare gynecologic sarcomas. Full article

Hearing loss is often caused by genetic and environmental factors, with inherited mutations responsible for 50–60% of cases. The GJB2 gene, encoding connexin 26, is a major contributor to nonsyndromic sensorineural hearing loss (NSHL) due to its role in cellular communication critical for auditory function. In Taiwan, common deafness-associated genes include GJB2, SLC26A4, OTOF, MYO15A, and MTRNR1, which were similar to those found in other populations. The most common pathogenic genes is GJB2 mutations and the hearing level in children with GJB2 p.V37I/p.V37I or p.V37I/c.235delC was estimated to deteriorate at approximately 1 decibel hearing level (dB HL)/year. We found another common mutation in Taiwan Biobank, GJB2 p.I203T, which were identified in our data and individuals carrying this mutation experienced more severe hearing loss, suggesting a synergistic effect of these mutations on auditory impairment. We suggest GJB2 whole genetic screening is recommended for clinical management and prevention strategies in Taiwan. This study used data from the Taiwan Biobank to analyze allele frequencies of GJB2 gene variants. Predictive software (PolyPhen-2 version 2.2, SIFT for missense variants 6.2.1, MutationTaster Ensembl 112 and Alphamissense CC BY-NC-SA 4.0) assessed the pathogenicity of specific mutations. Additionally, 82 unrelated NSHL patients were screened for mutations in these genes using PCR and DNA sequencing. The study explored the correlation between genetic mutations and the severity of hearing loss in patients. Several common GJB2 mutation sites were identified from the Taiwan Biobank, including GJB2 p.V37I (7.7%), GJB2 p.I203T (6%), GJB2 p.V27I (31%), and GJB2 p.E114G (22%). Bioinformatics analysis classified GJB2 p.I203T as pathogenic, while GJB2 p.V27I and GJB2 p.E114G were considered polymorphisms. Patients with GJB2 p.I203T mutation experienced more severe hearing loss, emphasizing the potential interaction between the gene in auditory impairment. The mutation patterns of GJB2 in the Taiwanese population are similar to other East Asian regions. Although GJB2 mutations represent the predominant genetic cause of hereditary hearing loss, the corresponding mutant proteins exhibit detectable aggregation, particularly at cell–cell junctions, suggesting at least partial trafficking to the plasma membrane. Genetic screening for these mutations—especially GJB2 p.I203T (6%), GJB2 p.V27I (31%), and GJB2 p.E114G (22%)—is essential for the effective diagnosis and management of non-syndromic hearing loss (NSHL) in Taiwan. We found GJB2 p.I203T which were identified in our data and individuals carrying this mutation experienced more severe hearing loss, suggesting a synergistic effect of these mutations on auditory impairment. We suggest whole GJB2 gene sequencing in genetic screening is recommended for clinical management and prevention strategies in Taiwan. These findings have significant clinical and public health implications for the development of preventive and therapeutic strategies. Full article

This study explores the use of machine learning models to assess the severity of Parkinson’s disease symptoms based on data from wearable and smartphone sensors. It presents models to predict the severities of individual symptoms—tremor, bradykinesia, stiffness, and dyskinesia—as well as the overall state of patients, using both clinician and patient self-assessments as labels. The dataset, although limited and imbalanced, enabled the identification of key trends. The best performance was achieved when combining data from both the MYO armband and smartphone, and when using patient self-assessments as targets. Tremor was the most predictable symptom, while others proved more challenging—especially at higher severity levels, which were poorly represented in the dataset. These results highlight the value of multimodal data and the importance of patient input in symptom monitoring. However, they also point to the need for more balanced and extensive datasets to improve prediction accuracy across all severity levels and symptoms. Full article