Search Results (302)

Dietary advanced glycation end-products (dAGEs) contained in high-sugar/fat and ultra-processed foods of the “Western diet” (WD) pattern predispose to several diseases by altering protein function or increasing oxidative stress and inflammation via RAGE (receptor for advanced glycation end-products). Although elevated endogenous AGEs are associated with loss of muscle mass and functionality (i.e., muscle wasting; MW), the impact of dAGEs on MW has not been elucidated. Here, we show that the most common dAGEs or their precursor, methylglyoxal (MGO), induce C2C12 myotube atrophy as endogenous AGE-derived BSA. ROS production, mitochondrial dysfunction, mitophagy, ubiquitin–proteasome activation, and inhibition of myogenic potential are common atrophying mechanisms used by MGO and AGE-BSA. Although of different origins, ROS are mainly responsible for AGE-induced myotube atrophy. However, while AGE-BSA activates the RAGE-myogenin axis, reduces anabolic mTOR, and causes mitochondrial damage, MGO induces glycolytic stress and STAT3 activation without affecting RAGE expression. Among thirty selected natural compounds, Vaccinium macrocarpon (VM), Camellia sinensis, and chlorophyll showed a surprising ability in counteracting in vitro AGE formation. However, only the standardized VM, containing anti-glycative metabolites as revealed by UHPLC-HRMS analysis, abrogates AGE-induced myotube atrophy. Collectively, our data suggest that WD-linked dAGE consumption predisposes to MW, which might be restricted by VM food supplements. Full article

The diagnostic algorithm for the demyelinating disorders of the central nervous system remains a work in progress, with the search for the ideal biomarkers ongoing. The so-called “ideal” biomarker should ensure the accurate differentiation between the most common demyelinating pathologies of the CNS and between the subtypes of the same pathology (for example, the conversion from relapsing–remitting multiple sclerosis to the secondary progressive phenotype). Advances in technology facilitated this research and in the following sections we will comprehensively review most of these, outlining the past, present, and prospects and the impact they had on both diagnosis and therapeutic approach. Full article

Peripheral nervous system (PNS) neurons, including motor neurons (MNs), possess a remarkable ability to regenerate and reinnervate target muscles following nerve injury. This process is orchestrated by a combination of intrinsic neuronal properties and extrinsic factors, with Schwann cells (SCs) playing a central role. Upon injury, SCs transition into a repair phenotype that allows axonal regeneration through molecular signaling and structural guidance. However, the identity of the SCs’ reprogramming factors is only partially known. We previously identified hydrogen peroxide (H₂O₂) as an early and key driver of nerve repair, inducing gene expression rewiring in SCs to support nerve re-growth. In this study, we quantitatively assessed the role of H₂O₂ in the activation of key pro-regenerative signaling pathways in SCs following sciatic nerve compression, specifically the extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun, which are essential for functional nerve recovery. Notably, we found that H₂O₂ neutralization does not impact degeneration, but it significantly affects the regenerative response. Collectively, our findings establish H₂O₂ as a promising regulator of the Schwann cell injury response at the injury site, linking oxidative signaling to the molecular mechanisms governing nerve regeneration. Full article

Background/Objectives: Parkinson’s disease (PD) and hypertension are often coexistent conditions that interact in entwined ways at various levels. Cardiovascular autonomic dysfunction (CAD), a non-motor feature of PD occurring across all stages, alters blood pressure (BP) regulation. Methods: We conducted a cross-sectional study enrolling patients with PD and primary hypertension, without diabetes mellitus or other causes of secondary CAD, aiming to characterize BP profiles/patterns by ambulatory BP monitoring. We also sought associations between different CAD phenotypes and PD characteristics, disability, and cardiovascular comorbidities. Results: We included 47 patients with a median age of 71 years, PD duration of 9 years, and Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score of 40. Diurnal and nocturnal BP values were within the reference range, but BP load was excessive. Almost one-third had neurogenic orthostatic hypotension (OH) and 80% were non-dippers. The overall burden of non-motor symptoms was significant in these phenotypes. Patients with neurogenic OH were more prone to constipation, anxiety, and urinary problems, whereas gustatory dysfunction, loss of libido, and erectile dysfunction were more frequently reported by non-dippers. No significant differences with regard to cognitive decline were identified in subjects with and without neurogenic OH. Neurogenic OH was symptomatic in 78% of the cases, whereas 56% of those with orthostatic symptoms did not have OH at repeated measurements. Conclusions: Neurogenic OH is an independent predictor of disability in patients with PD and hypertension, after adjusting for PD duration, Hoehn and Yahr stage, levodopa equivalent daily dose (LEDD), and Montreal Cognitive Assessment (MoCA) score. Full article

During skeletal muscle unloading, phosphoinositide 3-kinase (PI3K), and especially PI3K gamma (PI3Kγ), can be activated by changes in membrane potential. Activated IP3 can increase the ability of Ca²⁺ to enter the nucleus through IP3 receptors. This may contribute to the activation of transcription factors that initiate muscle atrophy processes. LY294002 inhibitor was used to study the role of PI3K in the ATP-dependent regulation of skeletal muscle signaling during three days of unloading. Inhibition of PI3K during soleus muscle unloading slows down the atrophic processes and prevents the accumulation of ATP and the expression of the E3 ubiquitin ligase MuRF1 and ubiquitin. It also prevents the increase in the expression of IP3 receptors and regulates the activity of Ca²⁺-dependent signaling pathways by reducing the mRNA expression of the Ca²⁺-dependent marker calcineurin (CaN) and decreasing the phosphorylation of CaMKII. It also affects the regulation of markers of anabolic signaling in unloaded muscles: IRS1 and 4E-BP. PI3K is an important mediator of skeletal muscle atrophy during unloading. Developing strategies for the localized skeletal muscle release of PI3K inhibitors might be one of the future treatments for inactivity and disease-induced muscle atrophy. Full article

Background and Clinical Significance: Sarcopenia, characterized by muscle loss and fat infiltration, poses a significant health burden for aging populations. Quantitative Color 2D and 3D radiodensitometry provides a powerful tool to monitor muscle quality and quantity through CT imaging. This study assessed the impact of a ten-year-long home-bed gym exercise intervention on muscle quality in an elderly subject using CT-derived radiodensitometric analysis. The study involved two comparative analyses: Study A, which compared knee-to-ankle CT scans of the subject between 2013 and 2023; and Study B, which compared the subject’s 2023 thigh CT scan with a cohort of 2500 elderly Icelandic individuals from the AGES-Reykjavik study. Case Presentation: A 70-year-old male began a home-based Full-Body In-Bed Gym exercise program in 2013. Quantitative muscle volume and radiodensity measurements were performed using CT at baseline and after ten years. Results: Study A shows significant improvements in muscle volume observed in the knee-to-ankle region, while a slower decline in radiodensity was noted, indicating substantial preservation of muscle quality despite the expected decay of ten-year aging. For instance, muscle volume increased by 15% in the left Soleus muscle and by 6% in the right Soleus muscle, while the average radiodensity decreased by 12–17 HU. The subject’s thigh muscle quality at 80-years-old is above the AGES-Reykjavik’s cohort average, with reduced fat infiltration. Conclusions: Long-term home Full-Body In-Bed Gym, a low-impact exercise, can mitigate aging sarcopenia, as evidenced by improved tissue radiodensity and muscle mass substantial preservation. This suggests potential applications in personalized healthcare strategies to enhance muscle preservation among aging populations. Full article

Congenital titinopathies reported to date show autosomal recessive inheritance and are caused by a variety of genomic variants, most of them located in metatranscript (MTT)-only exons. The aim of this study was to describe additional patients and establish robust genotype–phenotype associations in titinopathies. This study involved analyzing molecular, clinical, pathological, and muscle imaging features in 20 patients who had at least one pathogenic or likely pathogenic TTN variant in MTT-only exons, with onset occurring antenatally or in the early postnatal stages. The 20 patients with recessive inheritance exhibited a heterogeneous range of phenotypes. These included fetal lethality, progressive weakness, cardiac or respiratory complications, hyper-CKemia, or dystrophic muscle biopsies. MRI revealed variable abnormalities in different muscles. All patients presented severe congenital myopathy at birth, characterized by arthrogryposis (either multiplex or axial–distal) or neonatal hypotonia in most cases. This study provides detailed genotype–phenotype correlations in congenital titinopathies caused by mutations in MTT-only exons. The findings highlight the variability in clinical presentation and the severity of phenotypes associated with these specific genetic alterations. RNA-seq analyses provided valuable insights into the molecular consequences of TTN variants, particularly in relation to splicing defects and nonsense-mediated RNA decay. In conclusion, this study reinforces the genotype–phenotype correlations between congenital myopathies and variants in TTN MTT-only exons, improves their molecular diagnosis, and provides a better understanding of their pathophysiology. Full article

The coexistence of dementia and depression in older populations presents a complex clinical challenge, with each condition often exacerbating the other. Cognitive decline can intensify mood disturbances, and untreated or recurring depression accelerates neurodegenerative processes. As depression is a recognized risk factor for dementia, it is crucial to address both conditions concurrently to prevent further deterioration. Antidepressants are frequently used to manage depression in dementia patients, with some studies suggesting they offer neuroprotective benefits. These benefits include promoting neurogenesis, enhancing synaptic plasticity, and reducing neuroinflammation, potentially slowing cognitive decline. Additionally, antidepressants have shown promise in addressing Alzheimer’s-related pathologies by reducing amyloid-beta accumulation and tau hyperphosphorylation. However, treatment-resistant depression remains a significant challenge, particularly in older adults with cognitive impairment. Many do not respond well to standard antidepressant therapies due to advanced neurodegenerative changes. Conflicting findings from studies add to the uncertainty, with some research suggesting that antidepressants may increase dementia risk, especially when used in patients with undiagnosed early-stage dementia. This article aims to explore the intricate relationship between depression and dementia, examining the benefits and risks of antidepressant use. We highlight the urgent need for personalized, comprehensive treatment strategies that balance mental health improvement with cognitive protection. Full article

In most mammals, postural soleus muscles are involved in the maintenance of the stability of the body in the gravitational field of Earth. It is well established that immediately after a laboratory rat is exposed to conditions of weightlessness (parabolic flight) or simulated microgravity (hindlimb suspension/unloading), a sharp decrease in soleus muscle electrical activity occurs. However, starting from the 3rd day of mechanical unloading, soleus muscle electrical activity begins to increase and reaches baseline levels approximately by the 14th day of hindlimb suspension. This phenomenon, observed in the course of rat hindlimb suspension, was named the “spontaneous electrical activity of postural muscle”. The present review discusses spinal mechanisms underlying the development of such spontaneous activity of rat soleus muscle and the effect of this activity on intracellular signaling in rat soleus muscle during mechanical unloading. Full article

Vitamin E (Vit E) deficiency studies underline the relevance of this vitamin in skeletal muscle (SkM) homeostasis. The knowledge of the effectors and modulators of Vit E action in SkM cells is limited, especially in aging and chronic diseases characterized by a decline in musculoskeletal health. Vit E comprises eight fat-soluble compounds grouped into tocopherols and tocotrienols, which share the basic chemical structure but show different biological properties and potentials to prevent diseases. Vit E has antioxidant and non-antioxidant activities and both favorable and adverse effects depending on the specific conditions and tissues. In this review, we focus on the actual knowledge of Vit E forms in SkM functions and new potential signaling effectors (i.e., bioactive sphingolipids and myokines). The possible advantages of Vit E supplementation in counteracting SkM dysfunctions in sarcopenia and under microgravity will also be discussed. Full article

Recently, onychectomy, the “declaw” surgery in which all or part of the distal phalanges are removed, has been shown to have significant effects on the forearm muscles of felids. While this surgery should clearly affect the limb muscles (especially those that insert on the removed or modified bone), these effects have not been studied beyond felids or in the hindlimb. To that end, we herein evaluated the muscle architecture of a kinkajou (Potos flavus) that was declawed on all four of its limbs and compared its anatomy to that of intact specimens and the felid findings. As expected, some of the declawed kinkajou’s muscles were substantially different from those of the intact specimens, and as was seen in felids, its digital muscles appear to have been weaker. However, unlike in the felids, the declawed kinkajou had relatively larger forearm muscles. Also, contrary to expectation, the leg muscles of the declawed kinkajou were not substantially different, perhaps reflecting important differences in limb use. Future analyses should examine this anatomy in other declawed kinkajou specimens and also look at the effects of this surgery in other taxa, for instance, non-arboreal relatives of the kinkajou as well as other arboreal taxa. Full article

Purpose: This study examined lifespan changes in maximum tongue strength, swallowing time, and masseter activity during swallowing. It provides normative data with which to compare clinical assessments of orofacial myofunctional disorders (OMD) and oropharyngeal dysphagia (OPD). Method: 409 healthy participants without identified OMD or OPD (ages 5–79 years) provided instrumental measures of tongue strength and electromyographic measurements for oropharyngeal transit time and masseter activity during swallows of four boluses. Participants were placed in three broad age groups (5–15, 16–59, 60–79) for cross-sectional analysis. Results: Differences were found between age groups for tongue strength, such that the youngest group had significantly lower anterior tongue strength than the other groups, and lower posterior tongue strength than the 16–59 age group. Anterior tongue strength was significantly greater for males than females; posterior tongue strength did not differ significantly between the sexes. The youngest group had longer oropharyngeal transit times than either of the two older groups for most boluses. Swallowing transit time decreased in duration across the age groups, from youngest to oldest, for the 2.5 cc pudding bolus. Both right and left masseters differed in activation among tasks and age groups. The oldest age group had consistently greater levels of activation of the right masseter, and all groups had greater activation for the cracker bolus. Spearman rank-order correlations largely confirmed the inferential statistics and provided evidence of a relationship between tongue weakness and increased oropharyngeal transit time. Conclusion: Maximum tongue pressure generation and oropharyngeal timing measures support a developmental hypothesis, with lower tongue strength and longer swallowing transit times for children ages 5 through 15. The smaller pudding bolus provided the greatest differentiation among the age groups, which may prove to be a functional indicator for clinical evaluation. These results are largely consistent with existing data for tongue strength and oropharyngeal swallowing transit times. Full article