The use of three-dimensional primary human myospheres to explore skeletal muscle effects of in vivo krill oil supplementation.

Purpose: Supplementation with krill oil has shown effects on whole-body lipid and glucose metabolism, as well as on skeletal muscle strength and function. We previously showed that krill oil intervention in vivo promoted fatty acid metabolism and protein synthesis in cultured human myotubes in a two-dimensional (2D) model. The aim of this study was to explore the effects of krill oil supplementation in vivo in a 3D myosphere model, and to compare a the human skeletal muscle 3D cell model to a 2D model.

Newly-diagnosed rheumatoid arthritis patients have elevated levels of plasma extracellular vesicles with protein cargo altered towards inflammatory processes.

Extracellular vesicles (EVs) are implicated in rheumatoid arthritis (RA) but have mainly been assessed in RA patients taking disease modifying anti-rheumatic drugs. EVs are nanoparticles important in cell-cell communication and their molecular cargo are biomarker candidates. We characterized the protein profiles of EVs from blood plasma from newly diagnosed, treatment naïve RA patients (N = 32) and compared them to healthy controls (N = 20), by size exclusion chromatography-based EV enrichment coupled with high-resolution quantitative proteomics.

Identification of determinants for variability in mitochondrial biochemical complex activities.

Diagnostics of mitochondrial disease requires a combination of clinical evaluations and biochemical characterization. However, the large normal variation in mitochondrial complex activity limits the precision of biochemical diagnostics. Thus, identifying factors that contribute to such variations could enhance diagnostic accuracy.

Suppression of Spry1 reduces HIF1α-dependent glycolysis and impairs angiogenesis in BRAF-mutant cutaneous melanoma.

Background: About 50% of cutaneous melanoma (CM) harbors the activating BRAF mutation which exerts most of the oncogenic effects through the MAPK signaling pathway. In the last years, a number of MAPK modulators have been identified, including Spry1. In this context, we have recently demonstrated that knockout of Spry1 (Spry1) in BRAF-mutant CM led to cell cycle arrest and apoptosis, repressed cell proliferation in vitro, and reduced tumor growth in vivo.

Reduced lipid and glucose oxidation and reduced lipid synthesis in AMPKα2 myotubes.

Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation of metabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscle energy metabolism, myotube cultures were established from and mice. Myotubes from mice had lower basal oleic acid and glucose oxidation compared to myotubes from mice.

Sex-dependent efficacy of sphingosine-1-phosphate receptor agonist FTY720 in mitigating Huntington's disease.

Huntington's disease (HD) is a debilitating neurodegenerative disorder characterized by severe motor deficits, cognitive decline and psychiatric disturbances. An early and significant morphological hallmark of HD is the activation of astrocytes triggered by mutant huntingtin, leading to the release of inflammatory mediators. Fingolimod (FTY), an FDA-approved sphingosine-1-phosphate (S1P) receptor agonist is used to treat multiple sclerosis (MS), a neuroinflammatory disease, and has shown therapeutic promise in other neurological conditions.

Krill oil supplementation promotes increased fuel metabolism and protein synthesis in cultured human skeletal muscle cells.

Introduction: Krill oil is a dietary supplement derived from Antarctic krill; a small crustacean found in the ocean. Krill oil is a rich source of omega-3 fatty acids, specifically eicosapentaenoic acid and docosahexaenoic acid, as well as the antioxidant astaxanthin. The aim of this study was to investigate the effects of krill oil supplementation, compared to placebo oil (high oleic sunflower oil added astaxanthin), on energy metabolism and substrate turnover in human skeletal muscle cells.

Aerobic adaptation and metabolic dynamics of DSM 20271: insights from comparative transcriptomics and surfaceome analysis.

Unlabelled: () DSM 20271 is a bacterium known for its ability to thrive in diverse environments and to produce vitamin B12. Despite its anaerobic preference, recent studies have elucidated its ability to prosper in the presence of oxygen, prompting a deeper exploration of its physiology under aerobic conditions. Here, we investigated the response of DSM 20271 to aerobic growth by employing comparative transcriptomic and surfaceome analyses alongside metabolite profiling.

PCSK1N as a Tumor Size Marker and an ER Stress Response Protein in Corticotroph Pituitary Adenomas.

Context: Silent corticotroph adenoma (SCA) exhibits more tumor aggressiveness features than functioning adenomas (FCAs).

Objective: We aimed to investigate proprotein convertase subtilisin/kexin type 1 inhibitor (PCSK1N) expression in CA and examine if endoplasmic reticulum (ER) stress-induced responses affect cell survival in a corticotroph tumor cell model.

Methods: Clinical and imaging characteristics were recorded in 33 patients with FCA (20 women, 11 macroadenomas) and 18 SCAs (8 women, all macroadenomas).

Supernumerary proteins of the human mitochondrial ribosomal small subunit are integral for assembly and translation.

Mitochondrial ribosomes (mitoribosomes) have undergone substantial evolutionary structural remodeling accompanied by loss of ribosomal RNA, while acquiring unique protein subunits located on the periphery. We generated CRISPR-mediated knockouts of all 14 unique (mitochondria-specific/supernumerary) human mitoribosomal proteins (snMRPs) in the small subunit to study the effect on mitoribosome assembly and protein synthesis, each leading to a unique mitoribosome assembly defect with variable impact on mitochondrial protein synthesis. Surprisingly, the stability of mS37 was reduced in all our snMRP knockouts of the small and large ribosomal subunits and patient-derived lines with mitoribosome assembly defects.

Benchmarking and integrating human B-cell receptor genomic and antibody proteomic profiling.

Immunoglobulins (Ig), which exist either as B-cell receptors (BCR) on the surface of B cells or as antibodies when secreted, play a key role in the recognition and response to antigenic threats. The capability to jointly characterize the BCR and antibody repertoire is crucial for understanding human adaptive immunity. From peripheral blood, bulk BCR sequencing (bulkBCR-seq) currently provides the highest sampling depth, single-cell BCR sequencing (scBCR-seq) allows for paired chain characterization, and antibody peptide sequencing by tandem mass spectrometry (Ab-seq) provides information on the composition of secreted antibodies in the serum.

Time-dependent reduction in oxidative capacity among cultured myotubes from spinal cord injured individuals.

Background: Skeletal muscle adapts in reaction to contractile activity to efficiently utilize energy substrates, primarily glucose and free fatty acids (FA). Inactivity leads to atrophy and a change in energy utilization in individuals with spinal cord injury (SCI). The present study aimed to characterize possible inactivity-related differences in the energy metabolism between skeletal muscle cells cultured from satellite cells isolated 1- and 12-months post-SCI.

Ancestral allele of DNA polymerase gamma modifies antiviral tolerance.

Mitochondria are critical modulators of antiviral tolerance through the release of mitochondrial RNA and DNA (mtDNA and mtRNA) fragments into the cytoplasm after infection, activating virus sensors and type-I interferon (IFN-I) response. The relevance of these mechanisms for mitochondrial diseases remains understudied. Here we investigated mitochondrial recessive ataxia syndrome (MIRAS), which is caused by a common European founder mutation in DNA polymerase gamma (POLG1).

Identifying a core protein signature of small extracellular vesicles derived from B-cell precursor acute lymphoblastic leukaemia.

Acute paediatric leukaemia is diagnosed and monitored via bone marrow aspirate assessment of blasts as a measure of minimal residual disease. Liquid biopsies in the form of blood samples could greatly reduce the need for invasive bone marrow aspirations, but there are currently no blood markers that match the sensitivity of bone marrow diagnostics. Circulating extracellular vesicles (EVs) represent candidate biomarkers that may reflect the blast burden in bone marrow, and several studies have reported on the utility of EVs as biomarkers for adult haematological malignancies.

Interplay between Cultured Human Osteoblastic and Skeletal Muscle Cells: Effects of Conditioned Media on Glucose and Fatty Acid Metabolism.

The interplay between skeletal muscle and bone is primarily mechanical; however, biochemical crosstalk by secreted mediators has recently gained increased attention. The aim of this study was to investigate metabolic effects of conditioned medium from osteoblasts (OB-CM) on myotubes and vice versa. Human skeletal muscle cells incubated with OB-CM showed increased glucose uptake and oxidation, and mRNA expression of the glucose transporter () , while fatty acid uptake and oxidation, and mRNA expression of the fatty acid transporter were decreased.

Towards optimised extracellular vesicle proteomics from cerebrospinal fluid.

The proteomic profile of extracellular vesicles (EVs) from cerebrospinal fluid (CSF) can reveal novel biomarkers for diseases of the brain. Here, we validate an ultrafiltration combined with size-exclusion chromatography (UF-SEC) method for isolation of EVs from canine CSF and probe the effect of starting volume on the EV proteomics profile. First, we performed a literature review of CSF EV articles to define the current state of art, discovering a need for basic characterisation of CSF EVs.

Progressive mitochondrial dysfunction in cerebellar synaptosomes of cystatin B-deficient mice.

The involvement of mitochondrial dysfunction in cystatin B (CSTB) deficiency has been suggested, but its role in the onset of neurodegeneration, myoclonus, and ataxia in the CSTB-deficient mouse model () is yet unknown. CSTB is an inhibitor of lysosomal and nuclear cysteine cathepsins. In humans, partial loss-of-function mutations cause the progressive myoclonus epilepsy neurodegenerative disorder, EPM1.

and proteomics of biofilms and the development of biofilm-binding synthetic nanobodies.

The antibiotic-tolerant biofilms present in tuberculous granulomas add an additional layer of complexity when treating mycobacterial infections, including tuberculosis (TB). For a more efficient treatment of TB, the biofilm forms of mycobacteria warrant specific attention. Here, we used (Mmr) as a biofilm-forming model to identify the abundant proteins covering the biofilm surface.

Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation.

Lifestyle disorders like obesity, type 2 diabetes (T2D), and cardiovascular diseases can be prevented and treated by regular physical activity. During exercise, skeletal muscles release signaling factors that communicate with other organs and mediate beneficial effects of exercise. These factors include myokines, metabolites, and extracellular vesicles (EVs).

SENP2 knockdown in human adipocytes reduces glucose metabolism and lipid accumulation, while increases lipid oxidation.

Adipose tissue is one of the main regulative sites for energy metabolism. Excess lipid storage and expansion of white adipose tissue (WAT) is the primary contributor to obesity, a strong predisposing factor for development of insulin resistance. Sentrin-specific protease (SENP) 2 has been shown to play a role in metabolism in murine fat and skeletal muscle cells, and we have previously demonstrated its role in energy metabolism of human skeletal muscle cells.

A homozygous POLR1A variant causes leukodystrophy and affects protein homeostasis.

RNA polymerase I transcribes ribosomal DNA to produce precursor 47S rRNA. Post-transcriptional processing of this rRNA generates mature 28S, 18S and 5.8S rRNAs, which form the ribosomes, together with 5S rRNA, assembly factors and ribosomal proteins.

Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants.

Focal lesions of articular cartilage give rise to pain and reduced joint function and may, if left untreated, lead to osteoarthritis. Implantation of generated, scaffold-free autologous cartilage discs may represent the best treatment option. Here we compare articular chondrocytes (ACs) and bone marrow-derived mesenchymal stromal cells (MSCs) for their ability to make scaffold-free cartilage discs.