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Cell Apr 2022Skeletal muscle size is highly plastic and sensitive to a variety of stimuli. Muscle atrophy occurs as the result of changes in multiple signaling pathways that regulate...
Skeletal muscle size is highly plastic and sensitive to a variety of stimuli. Muscle atrophy occurs as the result of changes in multiple signaling pathways that regulate both protein synthesis and degradation. The signaling pathways that are activated or inhibited depend on the specific stimuli that are altered. To view this SnapShot, open of download the PDF.
Topics: Humans; Muscle, Skeletal; Muscular Atrophy; Signal Transduction
PubMed: 35487192
DOI: 10.1016/j.cell.2022.03.028 -
Nutrients Nov 2021The differential diagnosis and treatment of seronegative enteropathy, also termed seronegative villous atrophy (SNVA), is a clinical challenge. Although seronegative... (Review)
Review
The differential diagnosis and treatment of seronegative enteropathy, also termed seronegative villous atrophy (SNVA), is a clinical challenge. Although seronegative coeliac disease (CD) is a frequent cause of SNVA, the aetiology can include immune-mediated, inflammatory, infectious, and drug-related forms. As a misdiagnosis of SNVA can result in patients being unnecessarily placed on a lifelong strict gluten-free diet or even given incorrect immunosuppressive therapy, the aim of this paper is to provide an evidence-based and practical approach for the workup and management of SNVA.
Topics: Atrophy; Celiac Disease; Diagnosis, Differential; Diet, Gluten-Free; Humans; Intestinal Diseases; Intestinal Mucosa
PubMed: 34836279
DOI: 10.3390/nu13114027 -
Annals of Medicine Dec 2023() is recognized as a type I carcinogen in gastric cancer (GC). However, GC still occurs after eradication, and its diagnosis is more complicated. This study aimed to...
BACKGROUND
() is recognized as a type I carcinogen in gastric cancer (GC). However, GC still occurs after eradication, and its diagnosis is more complicated. This study aimed to summarize the characteristics of early GC (EGC) after eradication to help accurately identify EGC and avoid missed diagnosis and misdiagnosis.
METHODS
A total of 81 patients of EGC after eradication (Hp-eradicated group), resected by endoscopic submucosal dissection (ESD), and 105 cases of infection-related EGC (control group) were assessed. After propensity-score matching, the clinical characteristics, endoscopic manifestations, and histopathological features of the 62 matched patients in each group were analyzed. We also conducted specific analyses in combination with endoscopic and histopathological images.
RESULTS
There were more patients in the Hp-eradicated group who received proton pump inhibitor (PPI) for >1 year compared to the control group ( < 0.001). More patients at OLGA stages I-II before the diagnosis of EGC were in the control group ( = 0.045), especially at stage II. The mucosa in the Hp-eradicated group showed more moderate-to-severe atrophy ( = 0.047), map-like redness ( < 0.001) and mild activity ( < 0.001). The predominant histopathological types differed between the two groups ( < 0.001), and the majority of cases in the Hp-eradicated group were high-grade intraepithelial neoplasia (HGIN). Ki-67 expression was lower in the Hp-eradicated group ( = 0.025). But different eradication intervals of have little effect on the characteristics of EGC. Furthermore, PPI uses for >1 year ( = 0.005), mucosal map-like redness ( < 0.001), moderate mucosal atrophy ( = 0.017), and mild activity of gastric mucosa ( = 0.005) were independent characteristics of EGC after eradication.
CONCLUSION
Our multicenter study revealed that EGC after eradication was characterized by long-term PPI use, moderate mucosal atrophy, mucosal map-like redness, the mild activity of gastric mucosa, a higher proportion of HGIN cases, and lower levels of Ki-67.
Topics: Humans; Retrospective Studies; Helicobacter pylori; Stomach Neoplasms; Propensity Score; Ki-67 Antigen; Anti-Bacterial Agents; Helicobacter Infections; Proton Pump Inhibitors; Atrophy
PubMed: 37450336
DOI: 10.1080/07853890.2023.2231852 -
Annals of Clinical and Translational... Jan 2023Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a...
OBJECTIVE
Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice.
METHODS
Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay.
RESULTS
Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with sNfL-E included male sex, younger age, progressive disease subtype, diabetes mellitus, impaired renal function, and active smoking. Higher body mass index (BMI) was associated with lower odds of elevated sNfL. Active treatment with disease-modifying therapy was associated with lower odds of sNfL-E. MS participants with sNfL-E exhibited worse neurological function (patient-reported disability, walking speed, manual dexterity, and cognitive processing speed), lower brain parenchymal fraction, and higher T2 lesion volume. Longitudinal analyses revealed accelerated short-term rates of whole brain atrophy in sNfL-E participants and higher odds of new T2 lesion development, although both MS participants with or without sNfL-E exhibited faster rates of whole brain atrophy compared to HC. Findings were consistent in analyses examining age-normative sNfL Z-scores as a continuous variable.
INTERPRETATION
Elevated sNfL is associated with clinical disability, inflammatory disease activity, and whole brain atrophy in MS, but interpretation needs to account for comorbidities including impaired renal function, diabetes, and smoking.
Topics: Humans; Male; Biomarkers; Brain; Atrophy; Europe
PubMed: 36427295
DOI: 10.1002/acn3.51704 -
Journal of Cachexia, Sarcopenia and... Apr 2023Ageing is accompanied by an inexorable loss of muscle mass and functionality and represents a major risk factor for numerous diseases such as cancer, diabetes and... (Review)
Review
Ageing is accompanied by an inexorable loss of muscle mass and functionality and represents a major risk factor for numerous diseases such as cancer, diabetes and cardiovascular and pulmonary diseases. This progressive loss of muscle mass and function may also result in the insurgence of a clinical syndrome termed sarcopenia, exacerbated by inactivity and disease. Sarcopenia and muscle weakness yield the risk of falls and injuries, heavily impacting on health and social costs. Thus, screening, monitoring and prevention of conditions inducing muscle wasting and weakness are essential to improve life quality in the ageing modern society. To this aim, the reliability of easily accessible and non-invasive blood-derived biomarkers is being evaluated. C-terminal agrin fragment (CAF) has been widely investigated as a neuromuscular junction (NMJ)-related biomarker of muscle dysfunction. This narrative review summarizes and critically discusses, for the first time, the studies measuring CAF concentration in young and older, healthy and diseased individuals, cross-sectionally and in response to inactivity and physical exercise, providing possible explanations behind the discrepancies observed in the literature. To identify the studies investigating CAF in the above-mentioned conditions, all the publications found in PubMed, written in English and measuring this biomarker in blood from 2013 (when CAF was firstly measured in human serum) to 2022 were included in this review. CAF increases with age and in sarcopenic individuals when compared with age-matched, non-sarcopenic peers. In addition, CAF was found to be higher than controls in other muscle wasting conditions, such as diabetes, COPD, chronic heart failure and stroke, and in pancreatic and colorectal cancer cachectic patients. As agrin is also expressed in kidney glomeruli, chronic kidney disease and transplantation were shown to have a profound impact on CAF independently from muscle wasting. CAF concentration raises following inactivity and seems to be lowered or maintained by exercise training. Finally, CAF was reported to be cross-sectionally correlated to appendicular lean mass, handgrip and gait speed; whether longitudinal changes in CAF are associated with those in muscle mass or performance following physical exercise is still controversial. CAF seems a reliable marker to assess muscle wasting in ageing and disease, also correlating with measurements of appendicular lean mass and muscle function. Future research should aim at enlarging sample size and accurately reporting the medical history of each patient, to normalize for any condition, including chronic kidney disease, that may influence the circulating concentration of this biomarker.
Topics: Humans; Sarcopenia; Agrin; Hand Strength; Reproducibility of Results; Muscular Atrophy; Biomarkers; Renal Insufficiency, Chronic; Muscles
PubMed: 36772862
DOI: 10.1002/jcsm.13189 -
Alzheimer's Research & Therapy Nov 2023Understanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of...
BACKGROUND
Understanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of this study was to feature divergent symptom-deficit profiles in amnestic MCI (aMCI) and non-amnestic MCI (naMCI).
METHODS
T1 and DTI MRI data from a total of 158 older adults with 50 normal controls, 56 aMCI, and 52 naMCI were included. The voxel-wise gray matter volumes and the number of seed-based white matter fiber bundles were compared among these three groups. Furthermore, correlation and mediation analyses between the neuroimaging indices and cognitive measures were performed.
RESULTS
The aMCI with specific memory abnormalities was characterized by volumetric atrophy of the left hippocampus but not by damage in the linked white matter fiber bundles. Conversely, naMCI was characterized by both the altered volume of the right inferior frontal gyrus and the significant damage to fiber bundles traversing the region in all three directions, not only affecting fibers around the atrophied area but also distant fibers. Mediation analyses of gray matter-white matter-cognition showed that gray matter atrophy affects the number of fiber bundles and further affects attention and executive function. Meanwhile, fiber bundle damage also affects gray matter volume, which further affects visual processing and language.
CONCLUSIONS
The divergent structural damage patterns of the MCI subtypes and cognitive dysfunctions highlight the importance of detailed differential diagnoses in the early stages of pathological neurodegenerative diseases to deepen the understanding of dementia subtypes and inform targeted early clinical interventions.
Topics: Humans; Aged; Magnetic Resonance Imaging; Cognitive Dysfunction; Cerebral Cortex; Neurodegenerative Diseases; Dementia; Atrophy; Brain; Neuropsychological Tests
PubMed: 37957768
DOI: 10.1186/s13195-023-01335-1 -
International Journal of Molecular... May 2024Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which... (Review)
Review
Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle atrophy only. In this review, we summarize the data concerning unloading-induced fatigue in different muscles and different unloading models and provide several potential mechanisms of unloading-induced fatigue based on recent experimental data. The unloading-induced changes leading to increased fatigue include both neurobiological and intramuscular processes. The development of intramuscular fatigue seems to be mainly contributed by the transformation of soleus muscle fibers from a fatigue-resistant, "oxidative" "slow" phenotype to a "fast" "glycolytic" one. This process includes slow-to-fast fiber-type shift and mitochondrial density decline, as well as the disruption of activating signaling interconnections between slow-type myosin expression and mitochondrial biogenesis. A vast pool of relevant literature suggests that these events are triggered by the inactivation of muscle fibers in the early stages of muscle unloading, leading to the accumulation of high-energy phosphates and calcium ions in the myoplasm, as well as NO decrease. Disturbance of these secondary messengers leads to structural changes in muscles that, in turn, cause increased fatigue.
Topics: Humans; Muscle Fatigue; Animals; Muscle, Skeletal; Muscular Atrophy
PubMed: 38732203
DOI: 10.3390/ijms25094984 -
Nutrients Apr 2023Sarcopenia, a decrease in skeletal muscle mass and function caused by aging, impairs mobility, raises the risk of fractures, diabetes, and other illnesses, and severely...
Sarcopenia, a decrease in skeletal muscle mass and function caused by aging, impairs mobility, raises the risk of fractures, diabetes, and other illnesses, and severely affects a senior's quality of life. Nobiletin (Nob), polymethoxyl flavonoid, has various biological effects, such as anti-diabetic, anti-atherogenic, anti-inflammatory, anti-oxidative, and anti-tumor properties. In this investigation, we hypothesized that Nob potentially regulates protein homeostasis to prevent and treat sarcopenia. To investigate whether Nob could block skeletal muscle atrophy and elucidate its underlying molecular mechanism, we used the D-galactose-induced (D-gal-induced) C57BL/6J mice for 10 weeks to establish a skeletal muscle atrophy model. The findings demonstrated that Nob increased body weight, hindlimb muscle mass, lean mass and improved the function of skeletal muscle in D-gal-induced aging mice. Nob improved myofiber sizes and increased skeletal muscle main proteins composition in D-gal-induced aging mice. Notably, Nob activated mTOR/Akt signaling to increase protein synthesis and inhibited FOXO3a-MAFbx/MuRF1 pathway and inflammatory cytokines, thereby reducing protein degradation in D-gal-induced aging mice. In conclusion, Nob attenuated D-gal-induced skeletal muscle atrophy. It is a promising candidate for preventing and treating age-associated atrophy of skeletal muscles.
Topics: Mice; Animals; Galactose; Sarcopenia; Proteostasis; Quality of Life; Mice, Inbred C57BL; Muscular Atrophy; Muscle, Skeletal; Aging
PubMed: 37111020
DOI: 10.3390/nu15081801 -
Frontiers in Endocrinology 2023Age-related muscle atrophy and adipose accumulation begin to occur in young and middle-aged individuals, and exercise at an early age improves body composition....
BACKGROUND
Age-related muscle atrophy and adipose accumulation begin to occur in young and middle-aged individuals, and exercise at an early age improves body composition. Pyroptosis may play an essential role in age-related low-grade inflammation. This study aimed to explore the alleviation of muscle atrophy by weight-bearing training with increasing age inhibition of pyroptosis.
METHODS
Ninety 8-month-old male SD rats were randomly divided into three groups: (1) normal baseline group (N group, = 10), sacrificed after adaptive feeding; control group (C group, = 40); and weight-bearing running group (R group, = 40). Blood samples, adipose tissue (AT), and extensor digitorum longus (EDL) were collected after 8, 16, 24, and 32-weeks intervention.
RESULTS
The body weight, muscle mass, fat mass, plasma lipid, AT wet weight, adipocyte cross-sectional area (CSA), and apoptosis rates of AT and EDL were increased, while the muscle mass, wet weight, and fiber CSA of EDL were decreased by aging, which were reversed by exercise. Weight-bearing training promoted protein synthesis in EDL, inhibited protein degradation in EDL, and expression of pyroptotic key proteins in EDL and AT in rats.
CONCLUSION
Weight-bearing training improves body composition and alleviates age-related muscle atrophy in rats, and its mechanism may be related to the inhibition of pyroptosis in the EDL and AT and the improvement of muscle protein metabolism.
Topics: Male; Animals; Rats; Rats, Sprague-Dawley; Pyroptosis; Muscular Atrophy; Muscles; Adipose Tissue
PubMed: 37720530
DOI: 10.3389/fendo.2023.1202686 -
Diabetes & Metabolism Journal Sep 2022Type 2 diabetes mellitus (T2DM) is known to be associated with cognitive decline and brain structural changes. This study systematically reviews and estimates human... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Type 2 diabetes mellitus (T2DM) is known to be associated with cognitive decline and brain structural changes. This study systematically reviews and estimates human brain volumetric differences and atrophy associated with T2DM.
METHODS
PubMed, PsycInfo and Cochrane Library were searched for brain imaging studies reporting on brain volume differences between individuals with T2DM and healthy controls. Data were examined using meta-analysis, and association between age, sex, diabetes characteristics and brain volumes were tested using meta-regression.
RESULTS
A total of 14,605 entries were identified; after title, abstract and full-text screening applying inclusion and exclusion criteria, 64 studies were included and 42 studies with compatible data contributed to the meta-analysis (n=31,630; mean age 71.0 years; 44.4% male; 26,942 control; 4,688 diabetes). Individuals with T2DM had significantly smaller total brain volume, total grey matter volume, total white matter volume and hippocampal volume (approximately 1% to 4%); meta-analyses of smaller samples focusing on other brain regions and brain atrophy rate in longitudinal investigations also indicated smaller brain volumes and greater brain atrophy associated with T2DM. Meta-regression suggests that diabetes-related brain volume differences start occurring in early adulthood, decreases with age and increases with diabetes duration.
CONCLUSION
T2DM is associated with smaller total and regional brain volume and greater atrophy over time. These effects are substantial and highlight an urgent need to develop interventions to reduce the risk of T2DM for brain health.
Topics: Adult; Aged; Atrophy; Brain; Diabetes Mellitus, Type 2; Female; Humans; Magnetic Resonance Imaging; Male
PubMed: 35255549
DOI: 10.4093/dmj.2021.0189