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Seminars in Nephrology Mar 2023Muscle wasting (ie, atrophy) is a serious consequence of chronic kidney disease (CKD) that reduces muscle strength and function. It reduces the quality of life for CKD... (Review)
Review
Muscle wasting (ie, atrophy) is a serious consequence of chronic kidney disease (CKD) that reduces muscle strength and function. It reduces the quality of life for CKD patients and increases the risks of comorbidities and mortality. Current treatment strategies to prevent or reverse skeletal muscle loss are limited owing to the broad and systemic nature of the initiating signals and the multifaceted catabolic mechanisms that accelerate muscle protein degradation and impair protein synthesis and repair pathways. Recent evidence has shown how organs such as muscle, adipose, and kidney communicate with each other through interorgan exchange of proteins and RNAs during CKD. This crosstalk changes cell functions in the recipient organs and represents an added dimension in the complex processes that are responsible for muscle atrophy in CKD. This complexity creates challenges for the development of effective therapies to ameliorate muscle wasting and weakness in patients with CKD.
Topics: Humans; Quality of Life; Muscular Atrophy; Renal Insufficiency, Chronic; Muscle, Skeletal; Proteolysis
PubMed: 37611335
DOI: 10.1016/j.semnephrol.2023.151409 -
Biological Research Jun 2023Duchenne muscular dystrophy (DMD) is an X-linked lethal genetic disorder for which there is no effective treatment. Previous studies have shown that stem cell...
BACKGROUND
Duchenne muscular dystrophy (DMD) is an X-linked lethal genetic disorder for which there is no effective treatment. Previous studies have shown that stem cell transplantation into mdx mice can promote muscle regeneration and improve muscle function, however, the specific molecular mechanisms remain unclear. DMD suffers varying degrees of hypoxic damage during disease progression. This study aimed to investigate whether induced pluripotent stem cells (iPSCs) have protective effects against hypoxia-induced skeletal muscle injury.
RESULTS
In this study, we co-cultured iPSCs with C2C12 myoblasts using a Transwell nested system and placed them in a DG250 anaerobic workstation for oxygen deprivation for 24 h. We found that iPSCs reduced the levels of lactate dehydrogenase and reactive oxygen species and downregulated the mRNA and protein levels of BAX/BCL2 and LC3II/LC3I in hypoxia-induced C2C12 myoblasts. Meanwhile, iPSCs decreased the mRNA and protein levels of atrogin-1 and MuRF-1 and increased myotube width. Furthermore, iPSCs downregulated the phosphorylation of AMPKα and ULK1 in C2C12 myotubes exposed to hypoxic damage.
CONCLUSIONS
Our study showed that iPSCs enhanced the resistance of C2C12 myoblasts to hypoxia and inhibited apoptosis and autophagy in the presence of oxidative stress. Further, iPSCs improved hypoxia-induced autophagy and atrophy of C2C12 myotubes through the AMPK/ULK1 pathway. This study may provide a new theoretical basis for the treatment of muscular dystrophy in stem cells.
Topics: Mice; Animals; AMP-Activated Protein Kinases; Induced Pluripotent Stem Cells; Mice, Inbred mdx; Muscle Fibers, Skeletal; Muscle, Skeletal; Atrophy; Hypoxia; Autophagy; RNA, Messenger
PubMed: 37270528
DOI: 10.1186/s40659-023-00435-4 -
NeuroImage. Clinical 2022Volumetric magnetic resonance imaging (MRI) atrophy is a hallmark of Rasmussen's encephalitis (RE). Here, we aim to investigate voxel-wise gray matter (GM) atrophy in...
Volumetric magnetic resonance imaging (MRI) atrophy is a hallmark of Rasmussen's encephalitis (RE). Here, we aim to investigate voxel-wise gray matter (GM) atrophy in RE, and its associations with glucose hypometabolism and neurotransmitter distribution utilizing MRI and PET data. In this study, fifteen RE patients and fourteen MRI normal subjects were included in this study. Voxel-wise GM volume and glucose metabolic uptake were evaluated using structural MRI and FDG-PET images, respectively. Spatial Spearman's correlation was performed between GM atrophy of RE with FDG uptake alterations, and neurotransmitter distributions provided in the JuSpace toolbox. Compared with the control group, RE patients displayed extensive GM volume loss not only in the ipsilateral hemisphere, but also in the frontal lobe, basal ganglia, and cerebellum in the contralateral hemisphere. Within the RE group, the insular and temporal cortices exhibited significantly more GM atrophy on the ipsilesional than the contralesional side. FDG-PET data revealed significant hypometabolism in areas surrounding the insular cortices in the ipsilesional hemisphere. RE-related GM volumetric atrophy was spatially correlated with hypomebolism in FDG uptake, and with spatial distribution of the dopaminergic and serotonergic neurotransmitter systems. The spatial concordance of morphological changes with metabolic abnormalities suggest FDG-PET offers potential value for RE diagnosis. The GM alterations associated with neurotransmitter distribution map could provide novel insight in understanding the neuropathological mechanisms and clinical feature of RE.
Topics: Atrophy; Encephalitis; Gray Matter; Humans; Magnetic Resonance Imaging; Metabolome
PubMed: 34952352
DOI: 10.1016/j.nicl.2021.102918 -
Journal of Alzheimer's Disease : JAD 2022Apathy is highly frequent in behavioral variant frontotemporal dementia (bvFTD). It is presumed to involve different pathophysiological mechanisms and neuroanatomical...
BACKGROUND
Apathy is highly frequent in behavioral variant frontotemporal dementia (bvFTD). It is presumed to involve different pathophysiological mechanisms and neuroanatomical regions.
OBJECTIVE
We explored the hypothesis that subgroups showing distinct profiles of apathy and distinct patterns of atrophy within frontal lobes could be disentangled in bvFTD.
METHODS
Using data-driven clustering applied to 20 bvFTD patients, we isolated subgroups according to their profiles on the three subscales of the Dimensional Apathy Scale (DAS). We explored their apathy profiles and atrophy patterns. Apathy profiles were characterized through both subjective measures of apathy by questionnaires and measures including objective behavioral metrics. Atrophy patterns were obtained by voxel-based morphometry, contrasting each bvFTD subgroup with healthy controls (N = 16).
RESULTS
By clustering based on DAS dimensions, we disentangled three subgroups of bvFTD patients, with distinct apathy profiles and atrophy patterns. One subgroup, which presented the smallest pattern of atrophy (including orbitofrontal cortex) with a right asymmetry, was characterized by high self-reported emotional and initiation apathy and by a self-initiation deficit reversible by external guidance. In other subgroups showing more diffuse bilateral atrophies extending to lateral prefrontal cortex, apathy was not reversible by external guidance and more difficulty to focus on goal-management was observed, especially in the subgroup with the largest atrophy and highest levels of executive apathy.
CONCLUSION
Distinct clinical profiles of apathy, corresponding to distinct anatomical subtypes of bvFTD, were identified. These findings have implications for clinicians in a perspective of precision medicine as they could contribute to personalize treatments of apathy.
Topics: Humans; Atrophy; Cognition; Frontal Lobe; Frontotemporal Dementia; Magnetic Resonance Imaging; Neuropsychological Tests
PubMed: 36155506
DOI: 10.3233/JAD-220370 -
European Journal of Neurology Nov 2022Late-onset (LO) and early-onset (EO) dementia show neurobiological and clinical differences. Clinical and fluoro-deoxy-glucose positron emission tomography (FDG-PET)...
BACKGROUND AND PURPOSE
Late-onset (LO) and early-onset (EO) dementia show neurobiological and clinical differences. Clinical and fluoro-deoxy-glucose positron emission tomography (FDG-PET) features of LO and EO posterior cortical atrophy (LO_PCA, EO_PCA), the visual variant of Alzheimer's disease (AD), were compared. LO_PCA patients were also compared with a group of patients with LO typical AD (tAD).
METHODS
Thirty-seven LO_PCA patients (onset age ≥ 65 years), 29 EO_PCA patients and 40 tAD patients who all underwent a standard neuropsychological battery were recruited; PCA patients were also assessed for the presence of posterior signs and symptoms. Brain FDG-PET was available in 32 LO_PCA cases, 23 EO_PCA cases and all tAD cases, and their scans were compared with scans from 30 healthy elderly controls. Within the entire PCA sample FDG uptake was also correlated with age at onset as a continuous variable.
RESULTS
The main difference between the two PCA groups was a higher prevalence of Bálint-Holmes symptoms in EO cases, which was associated with the presence of severe bilateral occipito-temporo-parietal hypometabolism, whilst LO_PCA patients showed reduction of FDG uptake mainly in the right posterior regions. The latter group also showed mesial temporal hypometabolism, similarly to the tAD group, although with a right rather than left lateralization. Correlation analysis confirmed the association between older age and decreased limbic metabolism and between younger age and decreased left parietal metabolism.
CONCLUSIONS
The major involvement of the temporal cortex in LO cases and of the parietal cortex in EO cases reported previously within the AD spectrum holds true also for the visual variant of AD.
Topics: Aged; Alzheimer Disease; Atrophy; Fluorodeoxyglucose F18; Glucose; Humans; Positron-Emission Tomography
PubMed: 35950612
DOI: 10.1111/ene.15520 -
Clinical and Experimental Dermatology Dec 2022Oestrogen plays a vital role in maintaining a normal vulvovaginal epithelium, vaginal lubrication, as well as a healthy microbiome to ensure an acidic pH. The decrease... (Review)
Review
Oestrogen plays a vital role in maintaining a normal vulvovaginal epithelium, vaginal lubrication, as well as a healthy microbiome to ensure an acidic pH. The decrease in oestrogen levels in women going through menopause results in both physiological and physical changes of the genitourinary system, and more specifically the vulva. We conducted a literature review on the effects of low oestrogen levels on the physiology and function of the vulva and the vulvovaginal epithelium. 'Genitourinary syndrome of menopause' (GSM) is the term used to describe the signs and symptoms of a low oestrogen state. The symptoms and signs of GSM can overlap or coexist with other vulval dermatoses. Expert opinion is needed to diagnose and manage vulval dermatoses in menopause. This article will discuss the signs and symptoms of GSM, as well as the different management options available. Other vulval dermatoses that can be affected by hypo-oestrogenism are also reviewed.
Topics: Female; Humans; Vagina; Atrophy; Syndrome; Menopause; Estrogens; Skin Diseases
PubMed: 36103137
DOI: 10.1111/ced.15400 -
The Pan African Medical Journal 2023brain atrophy is the reduction of brain volume often accompanied with cognitive changes. Despite the availability of computerized-tomography (CT) scanners in Tanzania,...
INTRODUCTION
brain atrophy is the reduction of brain volume often accompanied with cognitive changes. Despite the availability of computerized-tomography (CT) scanners in Tanzania, little is known about the magnitude of brain atrophy, its associated confusion state and the risk factors in adults. This study aimed to fill those knowledge gaps.
METHODS
a retrospective cross-sectional hospital-based survey was conducted in northern Tanzania using a sample size of 384 CT images of adults who underwent brain CT scans in three referral hospitals. CT images were evaluated using a diagonal brain fraction (DBF) method to determine the presence of brain atrophy. Data for other covariates were also collected.
RESULTS
we report a prevalence of 60.67% for brain atrophy and 35% for the associated confusion state. Association between confusion state and brain atrophy was statistically significant (χ = 21.954, p<0.001). Brain atrophy was prognosticated by: age (adjusted OR: 1.11; 95% CI [1.05, 1.20], p<0.001), smoking (adjusted OR: 6.97; 95% CI [2.12, 26.19], p<0.001), alcohol-consumption (adjusted OR: 11.87; 95% CI [3.44, 40.81], p<0.001), hypertension (adjusted OR: 61.21; 95 CI [15.20, 349.43], p<0.001), type-2 diabetes mellitus (adjusted OR: 15.67; 95% CI [5.32, 52.77], p<0.001) and white matter demyelination (adjusted OR: 13.45; 95% CI [4.66, 44.25], p<0.001).
CONCLUSION
there is high prevalence of brain atrophy and associated confusion state among hospitalized adults in northern Tanzania. Reported prognostic factors for brain atrophy such as age, smoking, alcohol consumption, hypertension, type-2 diabetes mellitus and white matter demyelination could help focus interventions in this area.
Topics: Humans; Adult; Retrospective Studies; Prevalence; Tanzania; Cross-Sectional Studies; Risk Factors; Brain; Diabetes Mellitus, Type 2; Hypertension; Central Nervous System Diseases; Atrophy; Demyelinating Diseases; Magnetic Resonance Imaging
PubMed: 37346919
DOI: 10.11604/pamj.2023.45.1.36831 -
World Journal of Gastroenterology Mar 2022Research on celiac disease (CD) in northwest China is still in its infancy. At present, large-sample data on the epidemiological, clinical, and pathological...
BACKGROUND
Research on celiac disease (CD) in northwest China is still in its infancy. At present, large-sample data on the epidemiological, clinical, and pathological characteristics of CD are limited.
AIM
To investigate the epidemiological, clinical, and pathological characteristics of CD in northwest China.
METHODS
The clinical data of 2884 patients with gastrointestinal (GI) symptoms were retrospectively analyzed. Total immunoglobulin A (IgA) and anti-tissue transglutaminase (tTG) IgA levels were examined in all patients. Gastroscopy and colonoscopy were performed in patients with positive anti-tTG IgA and deficient total IgA levels. Atrophy of the duodenal and ileal villi was examined and histopathological examinations were performed. The modified Marsh-Oberhuber classification system was used to grade villous atrophy in the duodenum or distal ileum. The patients' () infection status was compared in terms of clinical presentation and Marsh grade. Statistical analyses were performed using the t-test or chi-square test.
RESULTS
Among the 2884 patients, 73 were positive for serum anti-tTG IgA, and 50 were diagnosed with CD. The CD detection rate was significantly higher in Kazakhs (4.39%) than in Uyghurs (2.19%), Huis (0.71%), and Hans (0.55%). The main symptoms of CD were chronic diarrhea, anorexia, anemia, fatigue, weight loss, sleep disorders, osteopenia, and osteoporosis. The body mass index of patients with CD was significantly lower than that of patients without CD. A total of 69 patients with positive serum anti-tTG IgA and two patients with deficient total IgA levels underwent GI endoscopy. Endoscopy revealed crypt hyperplasia and/or duodenal villous atrophy, mainly manifested as nodular mucosal atrophy, grooves, and fissures. The difference in infection rates was not statistically significant between CD and non-CD patients but was significantly different among CD patients with different Marsh grades.
CONCLUSION
Among the patients with GI symptoms in northwestern China, the prevalence of CD was more in the Uyghur and Kazakh populations. infection may be associated with CD severity.
Topics: Atrophy; Autoantibodies; Celiac Disease; Duodenum; Helicobacter Infections; Humans; Immunoglobulin A; Retrospective Studies; Transglutaminases
PubMed: 35431514
DOI: 10.3748/wjg.v28.i12.1272 -
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 -
The Journal of Medical Investigation :... 2020Critically ill patients exhibit prominent muscle atrophy, which occurs rapidly after ICU admission and leads to poor clinical outcomes. The extent of atrophy differs... (Review)
Review
Critically ill patients exhibit prominent muscle atrophy, which occurs rapidly after ICU admission and leads to poor clinical outcomes. The extent of atrophy differs among muscles as follows: upper limb: 0.7%-2.4% per day, lower limb: 1.2%-3.0% per day, and diaphragm 1.1%-10.9% per day. This atrophy is caused by numerous risk factors such as inflammation, immobilization, nutrition, hyperglycemia, medication, and mechanical ventilation. Muscle atrophy should be monitored noninvasively by ultrasound at the bedside. Ultrasound can assess muscle mass in most patients, although physical assessment is limited to almost half of all critically ill patients due to impaired consciousness. Important strategies to prevent muscle atrophy are physical therapy and electrical muscular stimulation. Electrical muscular stimulation is especially effective for patients with limited physical therapy. Regarding diaphragm atrophy, mechanical ventilation should be adjusted to maintain spontaneous breathing and titrate inspiratory pressure. However, the sufficient timing and amount of nutritional intervention remain unclear. Further investigation is necessary to prevent muscle atrophy and improve long-term outcomes. J. Med. Invest. 67 : 1-10, February, 2020.
Topics: Biomarkers; Critical Illness; Electric Stimulation Therapy; Humans; Muscular Atrophy; Physical Therapy Modalities; Ventilators, Mechanical
PubMed: 32378591
DOI: 10.2152/jmi.67.1