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peptide science.

Tanshinone-IIA Mediated Attenuation of Post-Infarction Myocardial Fibrosis via IL-33/ST-2 Signaling Changes in Rat Epicardial Adipose Tissue.

J Vis Exp

Kehan Gao, Xingming Xu, Minyan Sun +6 more

Myocardial infarction (MI), a severe form of coronary artery disease, often results in myocardial fibrosis, a key contributor to cardiac dysfunction and heart failure. Epicardial adipose tissue (EAT) is increasingly implicated in cardiovascular pathology through cytokine-mediated modulation of cardiac function. Tanshinone IIA (TanIIA), a lipophilic compound derived from Salvia miltiorrhiza, exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties. This study aimed to evaluate the therapeutic potential of TanIIA in attenuating post-MI myocardial fibrosis and to explore its underlying mechanisms using an integrative approach combining in vivo experiments and in silico analyses. A murine MI model was established, and molecular docking was employed to assess TanIIA binding to key components of the interleukin-33/growth stimulation expressed gene 2 (IL-33/ST2) signaling pathway. Our results showed that TanIIA treatment significantly enhanced cardiac function, reduced histological injury, and mitigated myocardial fibrosis, alongside decreased serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI). TanIIA also attenuated inflammatory responses and oxidative stress in the serum, myocardium, and EAT. Mechanistically, TanIIA downregulated IL-33 and ST2 expression, suppressed the myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) pathway, and reduced transforming growth factor-β1 (TGF-β1) levels. In silico analyses further revealed that TanIIA exhibited strong binding affinities for IL-33, ST2, MyD88, and NF-κB p65, with the most stable interaction predicted for ST2. Collectively, these findings indicate that TanIIA alleviates MI-induced myocardial fibrosis by modulating EAT-associated inflammation and oxidative stress, potentially via multi-target inhibition of the IL-33/ST2 axis. These results support TanIIA as a promising therapeutic candidate for the management of post-infarction myocardial fibrosis.

Fatty acid regulation of feeding in Caenorhabditis elegans reveals the potential ancestral origin of a GLP-1-like multiagonist signaling system.

Proc Natl Acad Sci U S A

Feimei Zhu, Jorge Iván Castillo-Quan, Takafumi Ogawa +11 more

Regulation of food intake in mammals is complex and controlled by an interplay between hedonic and homeostatic signals, including hormones like leptin, which senses fat storage and suppresses food intake. Caenorhabditis elegans lack leptin and leptin receptors but still exhibit controlled eating. Here, we show that in C. elegans eating can be regulated by a balance between saturated and monounsaturated fatty acids interacting with transcriptional pathways regulating lipid synthesis, c-AMP response element binding protein and AMP kinase. This effect is mediated at the endoplasmic reticulum through formation of phospholipids and activation of the IRE-1 sensor in the nervous system, which controls behavior through neuronal serotonin and the G-protein-coupled ligand/receptor pair PDF-1/PDFR-1. We show that this peptide/receptor pair may be an ancestral precursor of the whole family of GLP-1/GIP-related peptides and their receptors. Indeed, administration of a 37 amino acid peptide derived from PDF-1 resulted in a reduction in body weight and improved insulin sensitivity in mice. In worms, signaling through this pathway induced food-leaving behavior on concentrated food and roaming behavior on dispersed food, a state we have termed "food-apathy," paralleling pharmacologic effects of GLP-1/GIP-related peptides in humans. These findings highlight the potential evolutionary origin of this family of hormones and their receptors, and its link to metabolic and neuronal responses in control of feeding behavior.

Uncommon tumor, uncertain course: functional oncocytic adrenocortical neoplasm with mild autonomous cortisol secretion.

JCEM Case Rep

Fatima Hallak, Kendra Frey, Maria Ortega Abad +3 more

Oncocytic adrenocortical neoplasms are rare adrenal tumors that are usually discovered incidentally. Although most are nonfunctional, about one-third secrete hormones, most often cortisol. We present the case of a 59-year-old man with a right adrenal mass and long-standing, difficult-to-control hypertension. Biochemical testing revealed a 1 mg dexamethasone suppression test (DST) of 2.8 μg/dL (77.25 nmol/L) (reference range: <1.8 μg/dL; <50 nmol/L), a repeated 1 mg DST of 2.3 μg/dL (63.44 nmol/L), a baseline adrenocorticotropic hormone of 6.5 pg/dL (1.4 pmol/L) (reference range: 7.2-63.3 pg/mL; 1.6-13.9 pmol/L), and a dehydroepiandrosterone of 66.5 μg/dL (1.80 μmol/L) (reference range: 51.7-295 μg/dL; 1.4-8.0 μmol/L); consistent with mild autonomous cortisol secretion. Adrenal computed tomography (CT) showed a stable 21 mm indeterminate adrenal nodule with an unenhanced CT attenuation of 22 Hounsfield units. The patient underwent laparoscopic adrenalectomy, and pathology confirmed an oncocytic adrenocortical neoplasm of uncertain malignant potential. Postoperatively, a 1 mg DST was within normal limits, confirming the resolution of mild autonomous cortisol secretion. He is currently under surveillance with annual CT imaging. This case underscores the need to consider oncocytic adrenocortical neoplasms in the differential diagnosis of adrenal incidentalomas and highlights the importance of further research into this rare entity.

Growth hormone: Synthesis and regulation.

Vitam Horm

Pedro Iglesias, Fernando Guerrero-Pérez

Growth hormone (GH) plays an essential role in the regulation of postnatal growth and metabolism through both direct and GH-IGF-1 axis-mediated mechanisms. GH action involves a complex interplay of endocrine, paracrine and autocrine signals that affect multiple tissues and organs. This review addresses the molecular and physiological fundamentals of GH secretion and action, as well as the multiple factors that modulate it, including central and peripheral signals, metabolic variables, physiological and pharmacological states. The relevance of GH receptor signaling and intracellular pathways involved in tissue response is discussed, as well as the mechanisms of hormone resistance that may arise in different clinical contexts. GH secretion, which is pulsatile, is subject to strict regulation by the hypothalamic-pituitary system, involving GHRH, somatostatin and ghrelin, together with negative feedback from GH and IGF-1. In addition, factors such as sleep, nutrition, stress, age or sex contribute significantly to its physiological variability. The implications of the somatotropic axis in pathological conditions such as GH deficiency, acromegaly or GH insensitivity syndromes are also explored.

GH and GnRH-gonadotropin secretion.

Vitam Horm

Adriana De Sousa Lages, Valentim Lopes, Richard Anderson

The hypothalamic pituitary gonadal (HPG) and hypothalamic pituitary somatotropic (HPS) axes are interconnected, orchestrating growth, metabolism, and reproduction through reciprocal feedback. Growth hormone (GH) and insulin like growth factor 1 (IGF-1) stimulate gonadotropin releasing hormone (GnRH) and kisspeptin neurons, support luteinizing hormone release, and regulate gonadal steroidogenesis and gametogenesis. Conversely, sex steroids, particularly estradiol, potentiate GH secretion by sensitizing somatotrophs to growth hormone releasing hormone and enhancing ghrelin driven pathways. This crosstalk evolves across developmental stages, most prominently during puberty, when the synergistic rise of sex steroids, GH, and IGF-1 creates an anabolic environment driving linear growth, skeletal maturation, and reproductive competence. From a translational perspective, this interplay has important diagnostic and therapeutic implications. In short stature with delayed diagnosis, combined GH and GnRH analogue therapy may extend growth potential and improve adult height. In central or peripheral precocious puberty, particularly when growth velocity declines during GnRH analogue treatment, co-treatment can prevent growth deceleration and optimize stature. In reproductive medicine, GH has been explored as an adjuvant in assisted reproductive technologies, with evidence suggesting benefits in follicular recruitment, oocyte quality, embryo development, and endometrial receptivity, although consistent effects on live birth rates remain uncertain. Emerging strategies, including kisspeptin analogues, highlight opportunities to modulate reproductive and somatotropic axes simultaneously, offering potential interventions in hypogonadism and functional hypothalamic disorders. By integrating mechanistic insights with clinical application, the coordinated regulation of GnRH and GH illustrates how translational neuroendocrinology can bridge molecular discovery with diagnostic innovation and therapeutic progress in growth and reproductive health.

Acromegaly and histopathology.

Vitam Horm

Gabriela A Caballero, Teresa Ribalta, Iban Aldecoa

Acromegaly is a chronic disorder caused by sustained excess of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), most commonly due to GH-secreting pituitary neuroendocrine tumors (PitNETs), mainly limited to Pit-1 expressing lineages. Histopathology remains central to diagnosis, prognosis, and treatment planning. Among GH-secreting or somatotroph neoplasms, densely and sparsely granulated are the most relevant clinicopathological subgroups, as they show distinct morphological, radiological, and clinical profiles. Risk assessment is refined by combining routine histology with immunohistochemistry (IHC), including lineage factors, proliferative markers, and somatostatin receptor (SSTR) subtypes, as well as selected molecular tests. Some assays, such as standardized evaluation of SSTR expression, still require further validation. Radiological signs of invasion complement tissue findings and contribute to practical grading systems. Optimal care requires a multidisciplinary approach that integrates endocrine evaluation, high-quality MRI, and expert neuropathology, essential not only for routine care but also for recognizing atypical presentations of acromegaly, such as pituitary hyperplasia, or ectopic growth hormone-releasing hormone (GHRH) or GH secretion. The integration of clinical, pathological, and molecular information provides the foundation for accurate diagnosis and personalized therapy in acromegaly.

Lycium barbarum polysaccharides as prebiotics prevent colorectal cancer liver metastasis in non-alcoholic fatty liver disease by modulating gut microbiota-FGF21-PI3K-AKT axis.

Front Pharmacol

Shuai Zhao, Zhenyao Tan, Jiaxin Suo +1 more

Colorectal cancer liver metastasis (CRLM) is the leading cause of death in colorectal cancer, and nonalcoholic fatty liver disease (NAFLD) promotes CRLM. Lycium barbarum polysaccharides (LBPs), bioactive metabolites of the traditional medicinal plant Lycium barbarum L, inhibit the progression of colorectal cancer and NAFLD by regulating gut microbiota composition. However, their roles in preventing CRLM under NAFLD conditions remain unclear. This study aimed to investigate the preventive effect of LBPs on liver metastasis of colorectal cancer in the context of NAFLD and explore its potential mechanisms.

CIMT combined with BoNT-A regenerates skeletal muscle and improves upper limb function through activating IGF-1/FGFR2 axis in hemiplegic cerebral palsy.

Exp Neurol

You Wang, Qihong Wu, Xiuying Zhao +16 more

Hemiplegic cerebral palsy (HCP) is a prevalent cause of pediatric motor disability. Constraint-induced movement therapy (CIMT), when combined with botulinum neurotoxin type A (BoNT-A), improves upper limb function and social participation in individuals with HCP. However, the mechanisms underlying the combined interventions remain unclear.

Cathelicidin Links Visceral Fat Accumulation and Coronary Artery Disease.

Circ J

Motoki Taniguchi, Akira Taruya, Chie Kitahara +20 more

Visceral fat (VF), particularly epicardial adipose tissue (EAT), plays a crucial role in the development of coronary artery disease (CAD). Cathelicidin (LL37) is an antimicrobial peptide involved in innate immunity and has been implicated in inflammatory processes. However, the relationship between VF accumulation, cathelicidin, and atherosclerosis remains unclear.

Tirzepatide mitigates atherosclerosis progression and modulates oxLDL-mediated proatherogenic effects in macrophages: evidence for M1/M2 homeostasis restoration.

Arch Pharm Res

Mengjie Kang, HaoLin Ren, Yanru Zhen +10 more

Tirzepatide (TZP), a novel dual agonist of glucagon-like peptide (GLP)-1/glucose-dependent insulinotropic polypeptide (GIP) receptors (GLP-1R/GIPR), has been shown to reduce cardiovascular (CV) risk in patients with diabetes or obesity. This study investigated anti-atherosclerotic effects of TZP and the underlying mechanisms using apo E-/- mice and cultured macrophages. In the present study, apo E-/- mice were fed a high fat/high cholesterol (HF) diet with or without TZP treatment for 12 weeks. Atherosclerotic lesions, metabolic parameters, and M1/M2 macrophage homeostasis were assessed. In vitro, RAW264.7 and THP-1 macrophages were treated with oxLDL and TZP to evaluate foam cell formation, inflammation, and signaling pathways. The results showed that TZP significantly lowered body weight, plasma lipids, and atherosclerotic burden in vivo, and favorably modulated the expression of M1/M2 macrophage markers. ANCOVA suggested that the anti-atherosclerotic effect may be partially independent of metabolic improvements, although further studies are needed for confirmation. While these data support macrophage modulation as a key mechanism, other vascular cell types and plaque components likely contribute to the observed plaque-stabilizing effects. In vitro, TZP inhibited oxidized Low-density Lipoprotein (oxLDL)-induced cholesterol accumulation and foam cell formation, cluster of differentiation (CD) 36 expression and M1 inflammatory markers while promoting M2 markers. These effects were blocked by combined GLP-1R/GIPR antagonism and further confirmed in human THP-1 macrophages. Mechanistically, the anti-inflammatory effects and modulation of M1/M2 macrophage homeostasis by TZP were mediated via activating kruppel-like factor 4/the peroxisome proliferator-activated receptor γ pathway. Collectively, these findings indicate that TZP confers CV protection and anti-atherosclerotic benefits through both lipid-lowering dependent and independent mechanisms, highlighting its therapeutic potential for diabetic and obese patients who are at high risk of atherosclerotic CV diseases.

GLP-1 and dual GIP/GLP-1 agonists in obese patients with HFpEF: a systematic review and meta-analysis of RCTs.

BMC Cardiovasc Disord

Elhaitham Yasir Awad Musa, Amar Yasir Awad Musa

Saikosaponin D protects against isoproterenol-induced kidney injury in rats by regulating the intrarenal renin-angiotensin system.

Toxicol Appl Pharmacol

Xiaoli Yi, Shanshan Song, Huiru Yang +3 more

Saikosaponin D (SSD), a triterpene saponin isolated from Bupleurum falcatum, exhibits diverse pharmacological activities and has been shown to alleviate kidney-related diseases in rodent models. However, its effects on isoproterenol (ISO)-induced kidney injury and the underlying mechanisms have not been fully elucidated. Herein, SSD administration effectively mitigated ISO-induced kidney injury in Sprague-Dawley rats, as evidenced by improvements in renal function parameters (e.g., reduced plasma creatinine and blood urea nitrogen) and histopathological structure. Specifically, SSD significantly suppressed ISO-induced upregulation of inflammatory cytokines, fibrotic markers, and kidney injury biomarkers in renal tissues. SSD treatment downregulated renal expression of angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE), reduced renal ACE activity and urinary angiotensin II (AngII) excretion, and upregulated renal angiotensin-converting enzyme 2 (ACE2) activity (without altering its expression) while increasing urinary angiotensin 1-7 (Ang1-7) excretion. Notably, no significant changes in plasma AngII or Ang1-7 concentrations were observed, indicating SSD specifically modulates the intrarenal renin-angiotensin system. Functional validation experiments showed that co-administration of SSD with the ACE inhibitor enalapril or AngII type 1 receptor (AT1R) antagonist losartan further potentiated its protective effects against ISO-induced kidney injury. In contrast, co-treatment with the ACE2 inhibitor MLN-4760 or Mas receptor (MasR) antagonist A779 completely abrogated SSD's renoprotective effects. In conclusion, our findings demonstrate that SSD exerts renoprotective effects against ISO-induced kidney injury by inhibiting renal fibrosis and inflammation. Mechanistically, SSD shifts the intrarenal RAS balance from the pro-inflammatory/fibrotic ACE/AngII/AT1R axis to the protective ACE2/Ang1-7/MasR axis, providing a novel therapeutic target for ISO-related kidney damage.

Serum malondialdehyde predicts mortality in patients with acute heart failure.

Redox Biol

Marija Pinterić, Iva Klobučar, Margarete Lechleitner +7 more

Acute heart failure (AHF) is associated with high short- and long-term mortality, and early identification of patients at highest risk remains challenging despite the use of established biomarkers and clinical risk scores. Oxidative stress plays a central role in the pathophysiology of AHF but has been insufficiently investigated as a prognostic target. This study aimed to evaluate the prognostic value of serum oxidative stress biomarkers for predicting short- and long-term mortality in AHF patients and to determine whether they improve risk stratification beyond established tools.

From Regeneration to Analgesia: The Role of BPC-157 in Tissue Repair and Pain Management.

Int J Mol Sci

Claire Yuan, Ariana Demers, Victor Silva-Ortiz +7 more

Body Protective Compound-157 (BPC-157) is a synthetic pentadecapeptide derived from gastric proteins that has demonstrated notable reparative and anti-inflammatory properties across diverse preclinical models. Experimental evidence reveals that BPC-157 supports angiogenesis, collagen synthesis, fibroblast activity, and modulation of nitric oxide pathways, contributing to enhanced healing of muscle, tendon, ligament, bone, and gastrointestinal tissue. Studies also report reduced inflammatory cytokine activity, improved microvascular integrity, and beneficial effects on pain modulation through peripheral and dopaminergic mechanisms. Although animal data indicate favorable safety and pharmacokinetics, human research remains limited to small pilot studies investigating musculoskeletal pain, interstitial cystitis, and intravenous administration, all suggesting potential therapeutic value without reported major adverse effects. However, inconsistent preparation standards, limited clinical validation, and regulatory restrictions underscore the need for rigorous controlled trials. BPC-157 remains a promising candidate for regenerative medicine, yet comprehensive evaluation is required before clinical translation can be recommended.

Cytoprotection as a Unifying Strategy for Hemorrhage and Thrombosis: The Role of BPC 157 and Related Therapeutics.

Pharmaceuticals (Basel)

Predrag Sikiric, Ivan Barisic, Mario Udovicic +21 more

This review presents an innovative and timely exploration of how cytoprotection can serve as a cohesive therapeutic approach by which to address the hemorrhage-thrombosis paradox. Presenting counteraction of both hemorrhage and thrombosis as phase-dependent outcomes of vascular dysregulation, the manuscript synthesizes conceptual, experimental, and clinical evidence into a unified systems-level model focused on the stable gastric pentadecapeptide BPC 157, which acts as a cytoprotective mediator. In rodents, BPC 157 can simultaneously counteract hemorrhage and thrombosis without directly affecting the coagulation cascade (aggregometry, thromboelastometry). This cytoprotective framework (decreased hemorrhage, decreased thrombosis) stands with presentation of both hemorrhage and thrombosis in the wound, arrhythmias, and Virchow triad, and resolution of these disturbances. As proof of the concept (full cytoprotective effect), a vasoprotective cytoprotective mediator capable of bidirectional regulation, BPC 157, is effective for wound healing, arrhythmia control, and normalization of Virchow's triad (i.e., following major injuries, occlusion/occlusion-like syndromes). As a comparison from a cytoprotective (partial vs. full) standpoint, conventional agents-anticoagulants, antiplatelet drugs, and fibrinolytics-provide only partial protection by targeting isolated components of hemostasis. Beta blockers, calcium channel blockers, prostaglandins, NO modulators, ACE inhibitors, and statins each exert broader cytoprotective effects; however, these actions remain incomplete and context-dependent, typically unidirectional, dose-limited, or are achieved at the expense of opposing pathological risks. Contrarily, for BPC 157, decreased hemorrhage (including both anticoagulants and antiplatelet agents), decreased thrombosis, effective wound healing, arrhythmia control, and normalization of Virchow's triad involve preservation of endothelial integrity, normalization of microcirculation, modulation of the NO system, stabilization of hemostatic balance, and recruitment of adaptive collateral pathways. Nevertheless, reliance on preclinical models necessitates further clinical validation.

Growth Hormone-Releasing Peptide-6 (GHRP-6) Ameliorates Post-Infarct Ventricular Remodeling and Systolic Dysfunction in a Model of Permanent Coronary Ligation.

Pharmaceuticals (Basel)

Linlin Wang, Arielis Rodriguez-Ulloa, Jorge Berlanga-Acosta +7 more

Background/Objective: GHRP-6 is a GH secretagogue hexapeptide with expanding and promising cardioprotective effects. Having determined 0.4 mg/kg as the minimum effective dose for enhancing inotropy based on echocardiographic parameters in healthy rats, we implemented a non-reperfusion myocardial infarct model, with its consequent left ventricle wall thinning and ballooning, via permanent left descending coronary artery ligation. Methods: Rats were assigned to three groups: sham-operated/normal rats, infarcted + saline-treated control rats, and infarcted + GHRP-6-administration rats. Treatments were initiated post-surgery and continued for 7 days. On day 7, the animals were echocardiographically and histologically evaluated. For mitochondrial proteomic analysis, an additional 12 healthy rats were used. Six animals received GHRP-6 or normal saline and were observed for 6 h after the inoculation. Results: Here, we show that GHRP-6 attenuated myocardial tissue demise, reduced myocardial interstitial fibrosis/scarring, and integrally improved left ventricle physiology. The proteomic analysis indicated that the GHRP-6 cardioprotective effects may be theoretically mediated by the concerted upregulation of proteins/pathways involved in fatty acid beta-oxidation, apoptosis prevention pathways, antioxidant defenses, and mitochondrial metabolic reprogramming. Conclusions: GHRP-6 is a potent cardioprotective candidate attenuating morphological and functional outcomes caused by late ischemia.

Myrtenol from Lavender Essential Oil Possesses Neuroprotective Effects and Promotes Neurite Outgrowth by Potentially Targeting TrkA and IGF-1R in PC12 Cells.

Int J Mol Sci

Ting Jiang, Lan Xiang, Jianhua Qi

Alzheimer's disease (AD) is a prevalent chronic neurodegenerative disorder; the progression of this disease is driven by cellular determinants such as oxidative stress and dysregulated neurotrophic signaling. Lavender essential oil is traditionally used in aromatherapy for neuronal regulation and neuroprotection, suggesting its potential neuroprotective effects for chronic neurodegenerative disorders like AD. However, the key active constituents responsible for its benefits and the specific molecular pharmacological mechanisms remain unclear. In this study, we isolated myrtenol from lavender essential oil under the guidance of activity evaluation. Its neuroprotective effects were evaluated in PC12 cells via neurite outgrowth, anti-Aβ/H2O2 cytotoxicity, and antioxidant assays. Targets and pathways were explored using inhibitor experiments, cell thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and Western blot. Myrtenol significantly induced neurite outgrowth in PC12 cells and effectively mitigated cytotoxicity and oxidative stress damage induced by Aβ25-35 and H2O2. Mechanistic studies revealed that myrtenol's effects are associated with the modulation of tyrosine kinase receptor A (TrkA) and insulin-like growth factor-1 receptor (IGF-1R), activating phospholipase C (PLC)/protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways to jointly mediate neuroprotection effects against the pathology of AD. This study demonstrates that myrtenol as a highly active component of lavender essential oil possesses NGF-like neuritogenic activity and neuroprotective effects. It provides a foundation for understanding the cellular mechanisms of myrtenol as a small-molecule lead for further investigation in neurodegeneration-related research.

Satellite Glial Cells in Peripheral Nerve Injury and Regeneration.

Biomedicines

Linjia Hu, Haimin Lu, Yufan Shen +4 more

Satellite glial cells (SGCs) are morphologically unique peripheral glial cells that surround neuronal somas in sensory, sympathetic, and parasympathetic ganglia. Satellite glial cells communicate with neurons that they ensheathe and form a distinct structural and functional unit. Following peripheral nerve injury, satellite glial cells undergo remarkable morphological changes, including gliosis, and help regulate the microenvironment surrounding neuronal somas. The expression of many satellite glial cell markers such as glial fibrillary acidic protein (GFAP) and connexin-43, pro-inflammatory cytokines, and growth factors in satellite glial cells is altered in these cells. Injury responses of satellite glial cells, particularly the activation of peroxisome proliferator-activated receptor α (PPARα), contribute to enhanced axonal regeneration. Targeting satellite glial cells may therefore offer novel therapeutic strategies for the treatment of peripheral nerve injury.

Review of the Pathology of Muscle in Amyotrophic Lateral Sclerosis.

Int J Mol Sci

Matthew Katz, Thomas Robertson, Shyuan T Ngo +4 more

In amyotrophic lateral sclerosis (ALS), a central event is the withdrawal of the motor nerve terminal from its target muscle. Whether this defect is driven by faults in the motor neuron or faults that originate within the muscle remains an area of investigation. In this review, we focus on the pathological abnormalities that are found in skeletal muscle, focusing, when possible, on human ALS, with support from ALS animal models. We begin with an overview of skeletal muscle, including a review of muscle fiber type, motor units and the neuromuscular synapse. Next, we provide a description of the clinical and biomarker changes that occur in the muscles of patients with ALS. We provide an extensive account of the histopathological changes that are evident in ALS muscle, such as fiber type grouping, muscle inflammation, protein misfolding, mitochondrial dysfunction, and alterations in neuromuscular junctions and muscle satellite cells. Our review then concludes with an update of metabolic and molecular-genetic changes that are found in ALS muscle. The evidence shows that muscle can be an additional target for therapy in ALS, in combination with therapies targeting neurons and glia within the central nervous system (CNS).

Single-Cell RNA-Sequencing Reveals Cachectic Satellite Cell Population in Muscle of Male Mice With Cancer Cachexia.

J Cachexia Sarcopenia Muscle

Alex Brown, Nicolás Collao, Aisha Saleh +3 more

Cancer cachexia leads to decreases in body mass, lean mass and fat mass, decreased therapeutic potential and ~20% of cancer-related deaths. While several studies have demonstrated changes to components of the muscle microenvironment with cancer cachexia, none have comprehensively assessed changes to cellular dynamics across the duration of cachexia development.