Muscle Proteome Analysis of Facioscapulohumeral Dystrophy Patients Reveals a Metabolic Rewiring Promoting Oxidative/Reductive Stress Contributing to the Loss of Muscle Function.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the epigenetic de-repression of the double homeobox 4 (DUX4) gene, leading to asymmetric muscle weakness and atrophy that begins in the facial and scapular muscles and progresses to the lower limbs. This incurable condition can severely impair muscle function, ultimately resulting in a loss of ambulation. A thorough analysis of molecular factors associated with the varying degrees of muscle impairment in FSHD is still lacking.

Mass spectrometry proteomic profiling of postmortem human muscle degradation for PMI estimation.

The discovery of new methods for determining the post-mortem interval is of significant forensic interest. Mass spectrometry has enhanced the accuracy of assessing post-mortem protein decay, with skeletal muscle being the most studied substrate due to its intrinsic properties of postmortem decay. In this pilot study, human skeletal muscle tissue (iliopsoas) was harvested and allowed to decay under controlled temperature and humidity conditions at predetermined intervals.

Proteomic screening identifies PF4/Cxcl4 as a critical driver of myelofibrosis.

Despite increased understanding of the genomic landscape of Myeloproliferative Neoplasms (MPNs), the pathological mechanisms underlying abnormal megakaryocyte (Mk)-stromal crosstalk and fibrotic progression in MPNs remain unclear. We conducted mass spectrometry-based proteomics on mice with Romiplostim-dependent myelofibrosis to reveal alterations in signaling pathways and protein changes in Mks, platelets, and bone marrow (BM) cells. The chemokine Platelet Factor 4 (PF4)/Cxcl4 was up-regulated in all proteomes and increased in plasma and BM fluids of fibrotic mice.

Nitrosative Stress in Astronaut Skeletal Muscle in Spaceflight.

Long-duration mission (LDM) astronauts from the International Space Station (ISS) (>180 ISS days) revealed a close-to-normal sarcolemmal nitric oxide synthase type-1 (NOS1) immunoexpression in myofibers together with biochemical and quantitative qPCR changes in deep calf soleus muscle. Nitro-DIGE analyses identified functional proteins (structural, metabolic, mitochondrial) that were over-nitrosylated post- vs. preflight.

Proteomic analysis by mass spectrometry of postmortem muscle protein degradation for PMI estimation: A pilot study.

The determination of the postmortem interval is a topic of great forensic interest. The possibility of using new technologies has allowed the study of postmortem decay of biomolecules in the determination of PMI. Skeletal muscle proteins are promising candidates because skeletal muscle exhibits slower postmortem decay compared to other internal organs and nervous tissues, while its degradation is faster than cartilage and bone.

Space Omics and Tissue Response in Astronaut Skeletal Muscle after Short and Long Duration Missions.

The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International Space Station (ISS) astronauts.

Effects of Omega-3 and Antioxidant Cocktail Supplement on Prolonged Bed Rest: Results from Serum Proteome and Sphingolipids Analysis.

Physical inactivity or prolonged bed rest (BR) induces muscle deconditioning in old and young subjects and can increase the cardiovascular disease risk (CVD) with dysregulation of the lipemic profile. Nutritional interventions, combining molecules such as polyphenols, vitamins and essential fatty acids, can influence some metabolic features associated with physical inactivity and decrease the reactive oxidative and nitrosative stress (RONS). The aim of this study was to detect circulating molecules correlated with BR in serum of healthy male subjects enrolled in a 60-day BR protocol to evaluate a nutritional intervention with an antioxidant cocktail as a disuse countermeasure (Toulouse COCKTAIL study).

Molecular Fingerprint of BMD Patients Lacking a Portion in the Rod Domain of Dystrophin.

BMD is characterized by a marked heterogeneity of gene mutations resulting in many abnormal dystrophin proteins with different expression and residual functions. The smaller dystrophin molecules lacking a portion around exon 48 of the rod domain, named the D8 region, are related to milder phenotypes. The study aimed to determine which proteins might contribute to preserving muscle function in these patients.

Novel Insight into the Serum Sphingolipid Fingerprint Characterizing Longevity.

Sphingolipids (SLs) are structural components of the lipid bilayer regulating cell functions. In biological fluids, their distribution is sex-specific and is at variance in aging and many disorders. The aim of this study is to identify SL species associated with the decelerated aging of centenarians.

Novel Insight in Idiopathic Normal Pressure Hydrocephalus (iNPH) Biomarker Discovery in CSF.

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disease, causing motor and cognitive dysfunction and dementia. iNPH and Alzheimer's disease (AD) share similar molecular characteristics, including amyloid deposition, t-tau and p-tau dysregulation; however, the disease is under-diagnosed and under-treated. The aim was to identify a panel of sphingolipids and proteins in CSF to diagnose iNPH at onset compared to aged subjects with cognitive integrity (C) and AD patients by adopting multiple reaction monitoring mass spectrometry (MRM-MS) for sphingolipid quantitative assessment and advanced high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic analysis.

Skeletal Muscle Proteomic Profile Revealed Gender-Related Metabolic Responses in a Diet-Induced Obesity Animal Model.

Obesity is a chronic, complex pathology associated with a risk of developing secondary pathologies, including cardiovascular diseases, cancer, type 2 diabetes (T2DM) and musculoskeletal disorders. Since skeletal muscle accounts for more than 70% of total glucose disposal, metabolic alterations are strictly associated with the onset of insulin resistance and T2DM. The present study relies on the proteomic analysis of gastrocnemius muscle from 15 male and 15 female C56BL/J mice fed for 14 weeks with standard, 45% or 60% high-fat diets (HFD) adopting a label-free LC-MS/MS approach followed by bioinformatic pathway analysis.

Nitrosative Redox Homeostasis and Antioxidant Response Defense in Disused Muscle in Long-Term Bedrest (Toulouse Cocktail Study).

Increased oxidative stress by reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major determinant of disuse-induced muscle atrophy. Muscle biopsies (thigh vastus lateralis, ) obtained from healthy male subjects enrolled in the Toulouse Cocktail bedrest (BR) study were used to assess efficacy of an antioxidant cocktail (polyphenols, omega-3, vitamin E, and selenium) to counteract the increased redox homeostasis and enhance the antioxidant defense response by using label-free LC-MS/MS and NITRO-DIGE (nitrosated proteins), qPCR, and laser confocal microscopy. Label-free LC-MS/MS indicated that treatment prevented the redox homeostasis dysregulation and promoted structural remodeling (TPM3, MYH7, MYBPC, MYH1, MYL1, HRC, and LUM), increment of RyR1, myogenesis (CSRP3), and skeletal muscle development (MUSTN1, LMNA, AHNAK).

Muscle Proteomic Profile before and after Enzyme Replacement Therapy in Late-Onset Pompe Disease.

Mutations in the acidic alpha-glucosidase (GAA) coding gene cause Pompe disease. Late-onset Pompe disease (LOPD) is characterized by progressive proximal and axial muscle weakness and atrophy, causing respiratory failure. Enzyme replacement therapy (ERT), based on recombinant human GAA infusions, is the only available treatment; however, the efficacy of ERT is variable.

Proteomic insights on the metabolism in inflammatory bowel disease.

Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory conditions of the gut that include Crohn's disease and ulcerative colitis. The pathogenesis of IBD is not completely unraveled, IBD are multi-factorial diseases with reported alterations in the gut microbiota, activation of different immune cell types, changes in the vascular endothelium, and alterations in the tight junctions' structure of the colonic epithelial cells. Proteomics represents a useful tool to enhance our biological understanding and to discover biomarkers in blood and intestinal specimens.

Comparative proteomic analyses of Duchenne muscular dystrophy and Becker muscular dystrophy muscles: changes contributing to preserve muscle function in Becker muscular dystrophy patients.

Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are characterized by muscle wasting leading to loss of ambulation in the first or third decade, respectively. In DMD, the lack of dystrophin hampers connections between intracellular cytoskeleton and cell membrane leading to repeated cycles of necrosis and regeneration associated with inflammation and loss of muscle ordered structure. BMD has a similar muscle phenotype but milder.

Urinary physiology and hypoxia: a pilot study of moderate-altitude trekking effects on urodynamic indexes.

Exposure to high altitude is one of the most widely used models to study the adaptive response to hypoxia in humans. However, little is known about the related effects on micturition. The present study addresses the adaptive urinary responses in four healthy adult lowlanders, comparing urodynamic indexes at Kathmandu [1,450 m above sea level (a.

Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting.

The Sarcolab pilot study of 2 crewmembers, investigated before and after a 6-mo International Space Station mission, has demonstrated the substantial muscle wasting and weakness, along with disruption of muscle's oxidative metabolism. The present work aimed at evaluating the pro/anti-inflammatory status in the same 2 crewmembers (A, B). Blood circulating (c-)microRNAs (miRs), c-proteasome, c-mitochondrial DNA, and cytokines were assessed by real-time quantitative PCR or ELISA tests.

Erratum: Author Correction: Sarcolab pilot study into skeletal muscle's adaptation to longterm spaceflight.

[This corrects the article DOI: 10.1038/s41526-018-0052-1.].

ECM Remodeling in Breast Cancer with Different Grade: Contribution of 2D-DIGE Proteomics.

Tumor extracellular matrix (ECM) plays a pivotal role in outcome of breast cancer (BC) patients. Overexpression of 58 genes, encoding 43 structural ECM proteins, has been identified to determine a specific cluster of BC with accelerated metastatic potential only in the undifferentiated (grade III) phenotype. The scope of this study is to characterize protein repertoire able to predict patient outcome in BC according to ECM gene expression pattern and histological grade.

Sarcolab pilot study into skeletal muscle's adaptation to long-term spaceflight.

Spaceflight causes muscle wasting. The Sarcolab pilot study investigated two astronauts with regards to plantar flexor muscle size, architecture, and function, and to the underlying molecular adaptations in order to further the understanding of muscular responses to spaceflight and exercise countermeasures. Two crew members (A and B) spent 6 months in space.

Collagen VI Null Mice as a Model for Early Onset Muscle Decline in Aging.

Collagen VI is an extracellular matrix (ECM) protein playing a key role in skeletal muscles and whose deficiency leads to connective tissue diseases in humans and in animal models. However, most studies have been focused on skeletal muscle features. We performed an extensive proteomic profiling in two skeletal muscles (diaphragm and gastrocnemius) of wild-type and collagen VI null () mice at different ages, from 6- (adult) to 12- (aged) month-old to 24 (old) month-old.

Contribution of Extracellular Matrix and Signal Mechanotransduction to Epithelial Cell Damage in Inflammatory Bowel Disease Patients: A Proteomic Study.

This study utilizes 2D-DIGE (difference gel etrophoresis), isotope-coded protein labeling and biochemical assays to characterize protein alteration in ulcerative colitis (UC) and Crohn's disease (CD) in human epithelial cell and mucosal biopsies in inflammatory bowel disease (IBD)-affected patients. The aim of this study is to identify the key molecular signatures involved in epithelial cell structure of IBDs. In non-inflamed UC (QUC) keratins, vimentin, and focal adhesion kinase (7) increased, whereas vinculin and de-tyrosinated α-tubulin decreased; inflammation (IUC) exacerbated molecular changes, being collagen type VI alpha 1 chain (COL6A1), tenascin-C and vimentin increased.