obesity is a major global health concern tightly linked to insulin resistance and type 2 diabetes. Environmental exposure to endocrine-disrupting chemicals (EDs), including bisphenols (BPs) and perfluoroalkyl substances (PFs), has been implicated in metabolic dysfunction, yet the impact of chronic low-dose co-exposure on human adipocyte development and insulin responsiveness remains poorly defined. Here, we evaluated bisphenol S (BPS) and perfluorooctane sulfonate (PFOS), alone or combined, in human adipose-derived stem cells undergoing adipogenic differentiation. Cells were chronically exposed to environmentally relevant low doses of bisphenol S (BPS) and perfluorooctane sulfonate (PFOS), alone or in combination, throughout adipogenic differentiation. Lipid droplet accumulation was unchanged across conditions, indicating preserved terminal differentiation. In contrast, BPS and PFOS altered the timing and magnitude of key adipogenic transcriptional programs (CEBPA, PPARγ) and the mature adipocyte marker FABP4. PFOS and BPS+PFOS selectively increased IL1β expression in mature adipocytes, suggesting a limited pro-inflammatory shift. Functionally, all ED-treated groups showed reduced insulin-stimulated glucose uptake, associated with impaired GLUT4 translocation to the plasma membrane despite unchanged total GLUT4 levels. Notably, combined exposure produced the strongest defects in insulin signalling, reducing PI3K pathway activation and decreasing total AKT and ERK1/2 protein levels. In contrast, individually administered BPS and PFOS impaired glucose uptake without detectable PI3K alterations, suggesting the involvement of additional mechanisms. Overall, chronic low-dose exposure to BPS and PFOS disrupts adipocyte transcriptional and signalling networks, inducing features consistent with impaired insulin responsiveness and underscoring the importance of considering ED mixtures in metabolic risk assessment.

Bisphenol S (BPS) is widely used as a replacement for bisphenol A, yet accumulating evidence suggests that it has comparable endocrine and cardiovascular toxicity. Here, we investigated whether prolonged low-dose BPS exposure induces subtle but classifiable phenotypic alterations in human coronary artery endothelial cells (HCAEC), using an end-to-end experimental and ML pipeline that spans cell culture, high-content imaging, feature extraction, and robust classification. Cells were exposed to 0.1 µM BPS for 96 h and profiled using a cell painting assay and high-content microscopy. Image segmentation yielded ~2500 quantitative features per cell across four compartments—Membrane, Cytoplasm, Ring region (i.e., perinuclear region), and Nucleus—for multiple fluorophores. We systematically compared different classifiers (Random Forest, XGBoost, LASSO logistic regressor) using feature selection (MRMR, ReliefF, LASSO) or transformation-based dimensionality reduction (PCA, autoencoders). Tree-based ensembles robustly handled high-dimensional inputs, with XGBoost combined with ReliefF-selected features achieving the best performance. The most informative descriptors predominantly mapped to mitochondrial and nuclear channels, indicating early alterations in mitochondrial organisation and chromatin-related features. These findings show that chronic low-dose BPS exposure elicits a distinct endothelial phenotype, consistent with early endothelial dysfunction, and demonstrate that integrating high-content imaging with machine learning provides a sensitive, scalable framework for vascular toxicity assessment of environmental contaminants.

Glucocorticoids (GCs) are key regulators of stress responses and fetal maturation, and their physiological rise during pregnancy supports coordinated organ development. Clinically relevant GC exposure during sensitive windows of brain development occurs in several contexts, including antenatal treatment for risk of preterm birth to promote lung maturation, prolonged maternal therapy for chronic inflammatory or autoimmune conditions, and postnatal GC treatment in preterm infants, including regimens used to prevent or treat bronchopulmonary dysplasia. Although these contexts differ in timing, dose, and duration, they share the capacity to engage a glucocorticoid receptor (GR) signaling during critical windows of neurodevelopment, with possible long-term consequences for brain development and stress responsiveness. This review synthesizes clinical, experimental, and stem cell-based evidence to examine how GC signaling can shape brain structure and function across the lifespan. We discuss GR signaling in the central nervous system (CNS) and summarize evidence that sustained activation can be associated with paradoxical pro-inflammatory and neurotoxic phenotypes. We highlight epigenetic mechanisms through which GC signals may produce persistent changes in gene regulation, and we integrate data from prenatal exposure together with evidence on maternal metabolic and inflammatory context as modifiers of developmental risk. Finally, we propose an integrated view in which CNS outcomes attributed to GCs reflect a composite of direct neural actions and indirect effects shaped by peripheral tissues. We discuss adipose- and muscle-linked pathways as candidate mediators of systemic-to-central communication. This perspective links stress endocrinology, metabolism, and brain vulnerability, and highlights key mechanistic gaps and translational priorities for future research.

Endocrine disruptors (EDs) are environmental chemicals that interfere with hormone function, posing significant risks to human health, including the cardiovascular system. This review comprehensively examines the impact of EDs on cardiovascular health, with a specific focus on sex differences observed in various models. Utilizing in-vitro studies, in vivo animal models, and human clinical data, we delineate how sex-specific hormonal environments influence the cardiovascular effects of ED exposure. In vitro studies highlight cellular and molecular mechanisms that differ between male and female-derived cells. In vivo models reveal distinct physiological responses and susceptibilities to EDs, influenced by sex hormones. Human studies provide epidemiological evidence and clinical observations that underscore the variability in cardiovascular outcomes between men and women. This review underscores the necessity of considering sex as a critical factor in understanding the cardiovascular implications of ED exposure, advocating for gender-specific risk assessment and therapeutic strategies. The findings aim to enhance awareness and inform future research and policy-making to mitigate the adverse cardiovascular effects of EDs across different sexes.

IntroductionThe holistic development of elite athletes is a priority within European sports policies, necessitating a coordinated approach to dual career support. This study evaluated the perspectives of both university experts and student-athletes (S-As) on various dual career aspects, aiming to provide actionable insights for improving policies within European higher education institutions (HEIs).Materials and methodsData was collected through an online survey tailored for HEI experts and S-As across multiple countries. A total of 46 HEI experts and 321 S-As responded to the survey. The role of the country of origin on each dual career aspect for S-As was investigated using a MANOVA, followed by an ANOVA and post hoc analyses using Tukey's test when an effect emerged. The data from HEI experts and comparisons between S-As and HEI experts were handled descriptively due to the violation of assumptions of homogeneity of variances and sufficient sample size.ResultsThe study revealed significant trends and disparities in the availability and quality of support services. In particular, logistic, and financial support, and other support/policies areas showed a significant effect for S-As countries of origin, with Romanian and Serbian S-As generally reporting better scores and Italian and Spanish worse. In general, HEI experts rated dual career provision areas more favorably than S-As.ConclusionThis study underscores the importance of integrating both HEI expert and S-As' perspectives to develop effective dual career policies. Tailored interventions and enhanced communication about available resources are crucial for improving the dual career experiences of S-As across Europe.

Endocrine-disruptors (EDs), such as bisphenol-S (BPS) and perfluorooctane-sulfonate (PFOS), can cross the placental barrier and interfere with fetal development, inducing consequences that seem to be more pronounced in males. We investigated whether BPS and PFOS could have different effects on male and female human induced-pluripotent-stem cells (hiPSCs) by analyzing their impact on estrogen signaling pathways. Our results demonstrate that in male hiPSCs, BPS and PFOS induce alterations in the estrogen pathways, confirming their role as xenoestrogens. BPS and PFOS also upregulated oxidative phosphorylation proteins in males, while disruptions in Golgi apparatus integrity were observed in female cells. These findings highlight the differential susceptibility of male and female cells to ED exposure and suggest that such chemicals, perturbing the hormonal network, may affect developmental programming and long-term health. Moreover, this study emphasizes the importance of considering sex-specific responses to environmental pollutants and their impact during the highly sensitive periods of fetal growth.

ObjectivePrenatal exposure to environmental endocrine-disrupting chemicals (EDCs) has been increasingly linked to neurodevelopmental impairment. Bisphenol S (BPS) and perfluoro-octane sulfonate (PFOS), two widely distributed EDCs detected in maternal and fetal tissues, raise concern due to their potential to interfere with brain development even at low environmental doses.Methodsa phenotypic screening on human iPSC-derived cerebral organoids was performed to explore whether chronic exposure to BPS and PFOS could affect key neurodevelopmental processes.ResultsBoth compounds affected key neurodevelopmental processes, including neuronal proliferation, cortical specification, synaptogenesis, glutamatergic differentiation, mitochondrial function, and choroid plexus formation. Importantly, TUNEL assay confirmed the absence of significant cytotoxicity. BPS exposure was associated with reduced ERβ, GPER, and phosphorylated Akt expression, suggesting a possible involvement of estrogen-related pathways. PFOS exposure coincided with decreased transthyretin expression, suggesting a potential influence on thyroid hormone availability.ConclusionsExposure to multiple EDCs may disrupt distinct endocrine axes, producing cumulative impacts on human brain development. These findings underscore the value of human-relevant models for identifying endocrine-mediated neurodevelopmental hazards. While the observed molecular changes suggest distinct hormonal pathways may be involved, future mechanistic studies, including co-exposures with receptor modulators, will be required to establish causal relationships.

IntroductionObesity and overweight are linked to metabolic disturbances, which contribute to the onset of diseases like type 2 diabetes (T2D) and cardiovascular disorders. Metabolic health is also closely linked to autonomic function, as measured by heart rate variability (HRV), making HRV a potential non-invasive indicator of metabolic status. While studies have examined metabolic changes with body mass index (BMI), the link between HRV and specific metabolic profiles in normal-weight (NW), overweight (OW), and obese (OB) individuals is less understood. Additionally, whether HRV can reliably predict key metabolites associated with metabolic dysregulation remains largely unexplored.MethodsThis study uses targeted metabolomics to profile amino acids and acylcarnitines in a group of academic employees across BMI categories (NW, OW, and OB) and investigates correlations between HRV variables and these metabolites. Finally, a machine learning approach was employed to predict relevant metabolite levels based on HRV features, aiming to validate HRV as a non-invasive predictor of metabolic health.ResultsNW, OW, and OB subjects showed different metabolic profiles, as demonstrated by sparse partial least square discriminant analysis (sPLS-DA). The main upregulated metabolites differentiating NW from OB were C6DC and C8:1, while C6DC and C10:2 were higher in OW than NW. Time- and frequency-domain HRV features show a good correlation with the regulated metabolites. Finally, our machine learning approach allowed us to predict the most regulated metabolites in OB and OW subjects using HRV metrics.ConclusionOur study advances our understanding of the metabolic and autonomic changes associated with obesity and suggests that HRV could serve as a practical tool for non-invasively monitoring metabolic health, potentially facilitating early intervention in individuals with elevated BMI.

Small activating RNAs are short double-stranded RNAs designed to upregulate transcription of target genes. By this virtue, they can be used to restore expression of genes frequently silenced in cancer. AW1-51 (also referred to as CEBPA-51), the first small activating RNA therapeutic to enter clinical evaluation, has demonstrated biological activity and safety in Phase II trials for hepatocellular carcinoma, both as monotherapy and in combination with sorafenib, and in Phase 1a/1b in combination with pembrolizumab for patients with advanced solid tumors. It targets the master regulator CCAAT enhancer-binding protein alpha, abnormally silenced by DNA methylation in a wide range of hematological and non-hematological malignancies. However, the molecular events enabling this mechanism are only partially elucidated. In this study, we uncovered the molecular basis for AW1-51-induced transcriptional reactivation of CCAAT enhancer-binding protein alpha demonstrating that by directly promoting DNA demethylation of its promoter restores its expression, protein synthesis, and consequently cell differentiation. These findings unveil AW1-51 as a prototype for RNA-based precision medicine enabling conditional expression of CCAAT enhancer-binding protein alpha in diseases characterized by aberrant gene silencing and extending its potential therapeutic impact beyond cancer.

Dual career (DC) athletes face significant challenges in balancing dual demands of academic and athletic commitments. A scoping review of 25 studies published between 2014 and 2024 included data from over 3,000 student-athletes across 23 countries, with 88.5% focused on European contexts. Most adopted qualitative (52%) or quantitative (44%) approaches, with one study (4%) using a mixed method. Findings, synthesized using PRISMA guidelines, addressed logistical, social, financial, tutorship, curricula, and policy aspects. Recurring barriers included a lack of flexible educational programs, insufficient financial aid, and limited access to proximate sports and facilities. Social support systems, such as mentorship and institutional committees, emerged as essential for engagement and reducing isolation. European athletes frequently cited the need for improved financial support, highlighting scholarships and fee waivers. During the COVID-19 pandemic, e-learning strategies supported educational adherence and reduced stress, emphasizing their potential as flexible tool for addressing DC demands. However, disparities in policy implementation and service provision persist, with studies identifying cohesive institutional strategies for DC athletes. These findings underscore the need to develop harmonized frameworks across Europe, prioritizing integrated logistical planning, expanded financial support and tailored curricula. Broader perspectives from stakeholders are needed to enable DC athletes to thrive academically and athletically.

Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are examples of neurodegenerative movement disorders (NMDs), which are defined by a gradual loss of motor function that is frequently accompanied by cognitive decline. Although genetic abnormalities have long been acknowledged as significant factors, new research indicates that epigenetic alterations are crucial for the initiation and development of disease. This review delves into the complex interactions that exist between the pathophysiology of NMDs and epigenetic mechanisms such DNA methylation, histone modifications, and non-coding RNAs. Here, we examine how these epigenetic changes could affect protein aggregation, neuroinflammation, and gene expression patterns, thereby influencing the viability and functionality of neurons. Through the clarification of the epigenetic terrain underpinning neurodegenerative movement disorders, this review seeks to enhance comprehension of the underlying mechanisms of the illness and augment the creation of innovative therapeutic strategies.

Sleep quality is a vital component of one’s overall health and well-being. Inadequate sleep quality is linked to various adverse consequences, including cognitive decline, mood disruptions, and an elevated susceptibility to non-communicable diseases. Hence, it is crucial to precisely evaluate the quality of sleep, in order to identify individuals who are at risk and to develop successful interventions. Importantly, it has been shown that sleep quality can impact physiological processes even when a person is awake, leading to changes in heart rate variability (HRV). From this standpoint, the utilization of wearables and contactless technologies that can measure HRV without causing any discomfort is extremely well-suited for evaluating sleep quality. Nevertheless, there is a dearth of studies that analyze the correlation between HRV and sleep quality during waking. The aim of this study is to create a machine-(ML) learning model that uses HRV data to estimate sleep quality, as evaluated by the Pittsburgh Sleep Quality Index (PSQI). The measurement of HRV was conducted using a wearable photoplethysmography (PPG) sensor positioned on the fingertip. Subsequently, models were created to classify sleep quality based on the PSQI score. By employing the current approach, a classification good accuracy of 76.7

Regenerative medicine and tissue engineering aim to restore or replace impaired organs and tissues using cell transplantation supported by scaffolds. Recently scientists are focusing on developing new biomaterials that optimize cellular attachment, migration, proliferation, and differentiation. Nanoparticles, such as graphene oxide (GO), have emerged as versatile materials due to their high surface-to-volume ratio and unique chemical properties, such as electrical conductivity and flexibility. However, GO faces challenges such as cytotoxicity at high concentrations, a negative surface charge, and potential inflammatory responses; for these reasons, variations in synthesis have been studied. A GO derivative, Graphene Oxide-Polyethylenimine (GO-PEI), shows controlled porosity and structural definition, potentially offering better support for cell growth. Human amniotic fluid stem cells (hAFSCs) are a promising candidate for regenerative medicine due to their ability to differentiate into mesodermic and ectodermic lineages, their non-immunogenic nature, and ease of isolation. This study investigates the effects of GO and GO-PEI on hAFSCs, focusing on the effects on adhesion, proliferation, and metabolic features. Results indicate that GO-PEI restores cell proliferation and mitochondrial activity to control levels, with respect to GO that appeared less biocompatible. Both materials also influence the miRNA cargo of hAFSC-derived microvesicles, potentially influencing also cell-to-cell communication.

Sleep quality (SQ) is a crucial aspect of overall health. Poor sleep quality may cause cognitive impairment, mood disturbances, and an increased risk of chronic diseases. Therefore, assessing sleep quality helps identify individuals at risk and develop effective interventions. SQ has been demonstrated to affect heart rate variability (HRV) and skin temperature even during wakefulness. In this perspective, using wearables and contactless technologies to continuously monitor HR and skin temperature is highly suited for assessing objective SQ. However, studies modeling the relationship linking HRV and skin temperature metrics evaluated during wakefulness to predict SQ are lacking. This study aims to develop machine learning models based on HRV and skin temperature that estimate SQ as assessed by the Pittsburgh Sleep Quality Index (PSQI). HRV was measured with a wearable sensor, and facial skin temperature was measured by infrared thermal imaging. Classification models based on unimodal and multimodal HRV and skin temperature were developed. A Support Vector Machine applied to multimodal HRV and skin temperature delivered the best classification accuracy, 83.4%. This study can pave the way for the employment of wearable and contactless technologies to monitor SQ for ergonomic applications. The proposed method significantly advances the field by achieving a higher classification accuracy than existing state-of-the-art methods. Our multimodal approach leverages the synergistic effects of HRV and skin temperature metrics, thus providing a more comprehensive assessment of SQ. Quantitative performance indicators, such as the 83.4% classification accuracy, underscore the robustness and potential of our method in accurately predicting sleep quality using non-intrusive measurements taken during wakefulness.

EDITORIAL article Front. Cell Dev. Biol., 15 March 2023Sec. Epigenomics and Epigenetics Volume 11 - 2023 | https://doi.org/10.3389/fcell.2023.1164429

Endocrine disruptors (EDs), such as Bisphenols (BPs) and Perfluoroalkyls (PFs), are a class of plastic pollutants widely used in industrial applications. Human exposure to these molecules usually occurs through ingestion of contaminated food and water. Once entered the human body they can interfere with endogenous hormone signaling, leading to a wide spectrum of diseases. It has been reported that BPs and PFs can cross the placental barrier accumulating in the fetal serum, but the detrimental consequences for human development remain to be clarified. Here we analyze the effects of different doses of bisphenol A and S (BPA, BPS) perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on proliferation and mitochondrial health on different types of stem cells: through an integrated approach that combines data from pluripotent stem cells (hiPSCs) with that from the “environment” in which the embryo develops (fetal annexes-derived perinatal stem cells) we verified the potential developmental toxicity of the in utero EDs exposure. Data obtained showed that overall, BPs, and PFs tended to increase the proliferation rate of perinatal stem cells; a similar response was observed in hiPSCs exposed to very low doses of BPs and PFs, while at higher concentrations these chemicals were toxic; in addition, both the BPs and the PFs exerted a mitotoxic effects hiPSCs at all the concentration studied. All these data suggest that antenatal exposure to BPs and PFs, also at very low concentrations, may modify the biological characteristics of stem cells present in both the developing fetus and the fetal annexes, thus perturbing normal human development.

The present study investigates the impact of two endocrine disruptors, namely Bisphenols (BPs) and Perfluoroalkyls (PFs), on human stem cells. These chemicals leach from plastic, and when ingested through contaminated food and water, they interfere with endogenous hormone signaling, causing various diseases. While the ability of BPs and PFs to cross the placental barrier and accumulate in fetal serum has been documented, the exact consequences for human development require further elucidation. The present research work explored the effects of combined exposure to BPs (BPA or BPS) and PFs (PFOS and PFOA) on human placenta (fetal membrane mesenchymal stromal cells, hFM-MSCs) and amniotic fluid (hAFSCs)-derived stem cells. The effects of the xenobiotics were assessed by analyzing cell proliferation, mitochondrial functionality, and the expression of genes involved in pluripotency and epigenetic regulation, which are crucial for early human development. Our findings demonstrate that antenatal exposure to BPs and/or PFs may alter the biological characteristics of perinatal stem cells and fetal epigenome, with potential implications for health outcomes at birth and in adulthood. Further research is necessary to comprehend the full extent of these effects and their long-term consequences.

Parkinson’s disease (PD) is the second most common neurodegenerative disease and is characterized by the loss of midbrain dopaminergic neurons. Endocrine disrupting chemicals (EDCs) are active substances that interfere with hormonal signaling. Among EDCs, bisphenols (BPs) and perfluoroalkyls (PFs) are chemicals leached from plastics and other household products, and humans are unavoidably exposed to these xenobiotics. Data from animal studies suggest that EDCs exposure may play a role in PD, but data about the effect of BPs and PFs on human models of the nervous system are lacking. Previous studies demonstrated that machine learning (ML) applied to microscopy data can classify different cell phenotypes based on image features. In this study, the effect of BPs and PFs at different concentrations within the real-life exposure range (0.01, 0.1, 1, and 2 µM) on the phenotypic profile of human stem cell-derived midbrain dopaminergic neurons (mDANs) was analyzed. Cells exposed for 72 h to the xenobiotics were stained with neuronal markers and evaluated using high content microscopy yielding 126 different phenotypic features. Three different ML models (LDA, XGBoost and LightGBM) were trained to classify EDC-treated versus control mDANs. EDC treated mDANs were identified with high accuracies (0.88–0.96). Assessment of the phenotypic feature contribution to the classification showed that EDCs induced a significant increase of alpha-synuclein (αSyn) and tyrosine hydroxylase (TH) staining intensity within the neurons. Moreover, microtubule-associated protein 2 (MAP2) neurite length and branching were significantly diminished in treated neurons. Our study shows that human mDANs are adversely impacted by exposure to EDCs, causing their phenotype to shift and exhibit more characteristics of PD. Importantly, ML-supported high-content imaging can identify concrete but subtle subcellular phenotypic changes that can be easily overlooked by visual inspection alone and that define EDCs effects in mDANs, thus enabling further pathological characterization in the future.

Aims: Recent evidence supports non-class cardioprotective effects of metoprolol against neutrophil-mediated ischemia-reperfusion injury during exacerbated inflammation. Whether metoprolol exerts direct antiinflammatory effect on cardiomyocytes is unknown. Accordingly, we aimed to investigate the direct antiinflammatory effects of metoprolol in a cellular model of human induced pluripotent stem cell-derived cardiomyocytes (hiCMs) and to explore the role of beta-arrestin2 (beta-ARR2) biased agonism signaling pathway.Methods and results: hiCMs were treated with TNF-alpha for 24 h, followed by 4-hour treatment with metoprolol or esmolol. Electrical response of hiCMs to beta 1-selective blockade was assessed by microelectrode arrays technology. The effect on inflammatory and adhesion molecule expression was evaluated in wild-type and beta-ARR2 silenced hiCMs. To silence beta-ARR2 expression, hiCMs were transfected with a specific small interfering RNA targeting beta-ARR2 mRNA and preventing its translation.TNF-alpha stimulation boosted the expression of I kappa B, NF-kappa B, IL1 beta, IL6, and VCAM1 in hiCMs. TNF-alpha-treated hiCMs showed similar physiological responses to metoprolol and esmolol, with no difference in field potential duration and beat period recorded. Adding metoprolol significantly decreased inflammatory response patterns in wildtype hiCMs by dampening TNF-alpha induced expression of NF-kappa B, IL1 beta, and IL6, but not in beta-ARR2-knockout hiCMs. A similar response was not observed in presence of beta 1-selective blockade with esmolol. Conclusions: Metoprolol exerts a non-class direct anti-inflammatory effect on hi-CMs. beta 1-selective blockade with metoprolol disrupts inflammatory responses induced by TNF-alpha and induces significant inhibition of NF-kappa B signaling cascade via beta-ARR2 biased agonism. If confirmed at clinical level, metoprolol could be tested and repurposed to treat cardiac inflammatory disorders.

Skeletal muscle atrophy is represented by a dramatic decrease in muscle mass, and it is related to a lower life expectancy. Among the different causes, chronic inflammation and cancer promote protein loss through the effect of inflammatory cytokines, leading to muscle shrinkage. Thus, the availability of safe methods to counteract inflammation-derived atrophy is of high interest. Betaine is a methyl derivate of glycine and it is an important methyl group donor in transmethylation. Recently, some studies found that betaine could promote muscle growth, and it is also involved in anti-inflammatory mechanisms. Our hypothesis was that betaine would be able to prevent tumor necrosis factor-α (TNF-α)-mediated muscle atrophy in vitro. We treated differentiated C2C12 myotubes for 72 hr with either TNF-α, betaine, or a combination of them. After the treatment, we analyzed total protein synthesis, gene expression, and myotube morphology. Betaine treatment blunted the decrease in muscle protein synthesis rate exerted by TNF-α, and upregulated Mhy1 gene expression in both control and myotube treated with TNF-α. In addition, morphological analysis revealed that myotubes treated with both betaine and TNF-α did not show morphological features of TNF-α-mediated atrophy. We demonstrated that in vitro betaine supplementation counteracts the muscle atrophy led by inflammatory cytokines.