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Biomedicine & Pharmacotherapy =... Jul 2021Muscle atrophy and weakness are the adverse effects of long-term or high dose usage of glucocorticoids. In the present study, we explored the effects of fucoxanthin...
Muscle atrophy and weakness are the adverse effects of long-term or high dose usage of glucocorticoids. In the present study, we explored the effects of fucoxanthin (10 μM) on dexamethasone (10 μM)-induced atrophy in C2C12 myotubes and investigated its underlying mechanisms. The diameter of myotubes was observed under a light microscope, and the expression of myosin heavy chain (MyHC), proteolysis-related, autophagy-related, apoptosis-related, and mitochondria-related proteins was analyzed by western blots or immunoprecipitation. Fucoxanthin alleviates dexamethasone-induced muscle atrophy in C2C12 myotubes, indicated by increased myotubes diameter and expression of MyHC, decreased expression of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1). Through activating SIRT1, fucoxanthin inhibits forkhead box O (FoxO) transcriptional activity to reduce protein degradation, induces autophagy to enhance degraded protein clearance, promotes mitochondrial function and diminishes apoptosis. In conclusion, we identified fucoxanthin ameliorates dexamethasone induced C2C12 myotubes atrophy through SIRT1 activation.
Topics: Animals; Apoptosis; Atrophy; Autophagy; Cell Line; Cell Survival; Dexamethasone; Forkhead Box Protein O3; Mice; Muscle Fibers, Skeletal; Proto-Oncogene Proteins c-akt; Sirtuin 1; Xanthophylls
PubMed: 33865017
DOI: 10.1016/j.biopha.2021.111590 -
Cell Death & Disease May 2023Astrocyte atrophy is the main histopathological hallmark of major depressive disorder (MDD) in humans and in animal models of depression. Here we show that...
Astrocyte atrophy is the main histopathological hallmark of major depressive disorder (MDD) in humans and in animal models of depression. Here we show that electroacupuncture prevents astrocyte atrophy in the prefrontal cortex and alleviates depressive-like behaviour in mice subjected to chronic unpredictable mild stress (CUMS). Treatment of mice with CUMS induced depressive-like phenotypes as confirmed by sucrose preference test, tail suspension test, and forced swimming test. These behavioural changes were paralleled with morphological atrophy of astrocytes in the prefrontal cortex, revealed by analysis of 3D reconstructions of confocal Z-stack images of mCherry expressing astrocytes. This morphological atrophy was accompanied by a decrease in the expression of cytoskeletal linker Ezrin, associated with formation of astrocytic leaflets, which form astroglial synaptic cradle. Electroacupuncture at the acupoint ST36, as well as treatment with anti-depressant fluoxetine, prevented depressive-like behaviours, astrocytic atrophy, and down-regulation of astrocytic ezrin. In conclusion, our data further strengthen the notion of a primary role of astrocytic atrophy in depression and reveal astrocytes as cellular target for electroacupuncture in treatment of depressive disorders.
Topics: Humans; Mice; Animals; Depression; Antidepressive Agents; Astrocytes; Depressive Disorder, Major; Electroacupuncture; Hippocampus; Atrophy; Disease Models, Animal
PubMed: 37248211
DOI: 10.1038/s41419-023-05839-4 -
International Journal of Molecular... Oct 2020Intensive care unit-acquired weakness (ICUAW) occurs in critically ill patients stemming from the critical illness itself, and results in sustained disability long after... (Review)
Review
Intensive care unit-acquired weakness (ICUAW) occurs in critically ill patients stemming from the critical illness itself, and results in sustained disability long after the ICU stay. Weakness can be attributed to muscle wasting, impaired contractility, neuropathy, and major pathways associated with muscle protein degradation such as the ubiquitin proteasome system and dysregulated autophagy. Furthermore, it is characterized by the preferential loss of myosin, a distinct feature of the condition. While many risk factors for ICUAW have been identified, effective interventions to offset these changes remain elusive. In addition, our understanding of the mechanisms underlying the long-term, sustained weakness observed in a subset of patients after discharge is minimal. Herein, we discuss the various proposed pathways involved in the pathophysiology of ICUAW, with a focus on the mechanisms underpinning skeletal muscle wasting and impaired contractility, and the animal models used to study them. Furthermore, we will explore the contributions of inflammation, steroid use, and paralysis to the development of ICUAW and how it pertains to those with the corona virus disease of 2019 (COVID-19). We then elaborate on interventions tested as a means to offset these decrements in muscle function that occur as a result of critical illness, and we propose new strategies to explore the molecular mechanisms of ICUAW, including serum-related biomarkers and 3D human skeletal muscle culture models.
Topics: Animals; COVID-19; Coronavirus Infections; Critical Care; Humans; Iatrogenic Disease; Muscle Weakness; Muscular Atrophy; Pandemics; Pneumonia, Viral
PubMed: 33105809
DOI: 10.3390/ijms21217840 -
International Journal of Molecular... Sep 2020Sarcopenia is primarily characterized by skeletal muscle disturbances such as loss of muscle mass, quality, strength, and physical performance. It is commonly seen in... (Review)
Review
Sarcopenia is primarily characterized by skeletal muscle disturbances such as loss of muscle mass, quality, strength, and physical performance. It is commonly seen in elderly patients with chronic diseases. The prevalence of sarcopenia in chronic heart failure (HF) patients amounts to up to 20% and may progress into cardiac cachexia. Muscle wasting is a strong predictor of frailty and reduced survival in HF patients. Despite many different techniques and clinical tests, there is still no broadly available gold standard for the diagnosis of sarcopenia. Resistance exercise and nutritional supplementation represent the currently most used strategies against wasting disorders. Ongoing research is investigating skeletal muscle mitochondrial dysfunction as a new possible target for pharmacological compounds. Novel agents such as synthetic ghrelin and selective androgen receptor modulators (SARMs) seem promising in counteracting muscle abnormalities but their effectiveness in HF patients has not been assessed yet. In the last decades, many advances have been accomplished but sarcopenia remains an underdiagnosed pathology and more efforts are needed to find an efficacious therapeutic plan. The purpose of this review is to illustrate the current knowledge in terms of pathogenesis, diagnosis, and treatment of sarcopenia in order to provide a better understanding of wasting disorders occurring in chronic heart failure.
Topics: Aged; Aged, 80 and over; Cachexia; Chronic Disease; Exercise; Heart Failure; Humans; Middle Aged; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Sarcopenia
PubMed: 32911600
DOI: 10.3390/ijms21186549 -
The Journal of Pathology Apr 2022Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with...
Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5-alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI-treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI-induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF-κB signaling and anti-apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3-1 expression. In addition, club-like cells within regions of 5ARI-induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI-treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell-like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.
Topics: 5-alpha Reductase Inhibitors; Atrophy; Dihydrotestosterone; Humans; Lower Urinary Tract Symptoms; Male; Prostate; Prostatic Hyperplasia
PubMed: 34928497
DOI: 10.1002/path.5857 -
British Journal of Pharmacology Jul 2022The mineralocorticoid receptor (MR or NR3C2) is expressed in all types of cells from the different skin compartments. The binding and activation by glucocorticoids has a... (Review)
Review
The mineralocorticoid receptor (MR or NR3C2) is expressed in all types of cells from the different skin compartments. The binding and activation by glucocorticoids has a higher affinity than that on the closely related glucocorticoid receptor (GR or NR3C1). As both corticosteroid receptors are co-express in the skin and considering the therapeutic relevance of glucocorticoids to combat skin inflammatory diseases, it was proposed that several of the major side effects of topical glucocorticoids, such as skin atrophy and delayed wound healing, were due to unintended activation of the MR. Indeed, cutaneous MR blockade using genetic and pharmacological approaches in mice and human reduced corticosteroid-associated skin atrophy in conditions of endogenous and pharmacological glucocorticoid excess. Although data support the safety of topical MR antagonists combined with glucocorticoid, it is crucial to address the efficacy of treatment in skin inflammatory conditions and its impact on the overall metabolism. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.
Topics: Animals; Atrophy; Glucocorticoids; Humans; Mice; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; Skin; Skin Diseases
PubMed: 34788475
DOI: 10.1111/bph.15736 -
Pathology Jan 2021The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance... (Review)
Review
The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance and many do not need to be reported. Their clinical relevance lies in the risk that they are misinterpreted as cancer. This review presents the histopathological features of benign mimics and discusses their distinction from cancer. The lesions that are most often misdiagnosed as cancer are atrophy and its variants, including simple atrophy, partial atrophy and post-atrophic hyperplasia. Benign proliferations are a group of lesions with crowded small glands with no or little nuclear atypia. The most problematic entity of this group is adenosis, which may have a more alarming architecture than some cancers. A diagnostic problem with atrophy and several of the benign proliferations is that the glands often have a discontinuous or absent basal cell layer. Hyperplastic and metaplastic lesions include basal cell hyperplasia. Basal cell hyperplasia may especially mimic prostate cancer with its small dark glands, variable nuclear atypia and a pseudoinfiltrative pattern, which may be present. The anatomical structure that most often causes diagnostic problems is the seminal vesicle. The mucosa of the seminal vesicle contains small acini, often with very pronounced nuclear atypia that may be misinterpreted as cancer. Pathologists need to be familiar with these mimics, as a false positive diagnosis of prostate cancer may lead to unnecessary radical treatment.
Topics: Adenocarcinoma; Atrophy; Diagnosis, Differential; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms
PubMed: 33070957
DOI: 10.1016/j.pathol.2020.08.006 -
The Pan African Medical Journal 2021
Topics: Atrophy; Brain; Brain Diseases; Humans; Magnetic Resonance Imaging; Seizures
PubMed: 34707757
DOI: 10.11604/pamj.2021.39.256.30993 -
CMAJ : Canadian Medical Association... Dec 2023
Topics: Humans; Young Adult; Adult; Hockey; Rotator Cuff; Muscular Atrophy
PubMed: 38049167
DOI: 10.1503/cmaj.230792-f -
American Journal of Physiology.... Jul 2022Skeletal muscle is an integral tissue system that plays a crucial role in the physical function of all vertebrates and is a key target for maintaining or improving... (Review)
Review
Skeletal muscle is an integral tissue system that plays a crucial role in the physical function of all vertebrates and is a key target for maintaining or improving health and performance across the lifespan. Based largely on cellular and animal models, there is some evidence that various forms of heat stress with or without resistance exercise may enhance skeletal muscle growth or reduce its loss. It is not clear whether these stimuli are similarly effective in humans or meaningful compared with exercise alone across various heating methodologies. Furthermore, the magnitude by which heat stress may influence whole body thermoregulatory responses and the connection to skeletal muscle adaptation remains ambiguous. Finally, the underlying mechanisms, which may include interaction between relevant heat shock proteins and intracellular hypertrophy and atrophy related factors, remain unclear. In this narrative review, we examine the relevant literature regarding heat stress alone or in combination with resistance exercise emphasizing skeletal muscle hypertrophy and atrophy across cellular and animal models, as well as human investigations. In addition, we present working mechanistic theories for heat shock protein-mediated signaling effects regarding hypertrophy and atrophy-related signaling processes. Importantly, continued research is necessary to determine the practical effects and mechanisms of heat stress with and without resistance exercise on skeletal muscle function via growth and maintenance.
Topics: Animals; Atrophy; Exercise; Heat-Shock Proteins; Heat-Shock Response; Hypertrophy; Muscle, Skeletal; Muscular Atrophy
PubMed: 35536704
DOI: 10.1152/ajpregu.00048.2022