Loss of skeletal muscle mass and strength is a debilitating consequence various chronic diseases, inflammatory myopathies, neuromuscular disorders. Inflammation plays major role in the perpetuation myopathy degenerative diseases. TAK1 signaling protein that mediates activation multiple pathways response to cytokines microbial products. Recent studies have demonstrated essential for growth maintenance adult mice. However, effects overstimulation activity regulation remain unknown. In present...

Skeletal muscle wasting causes both morbidity and mortality of cancer patients. Accumulating evidence suggests that the markers endoplasmic reticulum (ER) stress unfolded protein response (UPR) pathways are increased in skeletal under multiple catabolic conditions, including cancer. However, signaling mechanisms role individual arms UPR regulation mass remain largely unknown. In present study, we demonstrated gene expression Toll-like receptors (TLRs) myeloid differentiation primary 88...

Abstract Skeletal muscle mass is regulated through coordinated activation of multiple signaling pathways. TAK1 signalosome has been found to be activated in various conditions atrophy and hypertrophy. However, the role mechanisms by which regulates skeletal remain less understood. Here, we demonstrate that supraphysiological adult mice stimulates translational machinery, protein synthesis, myofiber growth. causes phosphorylation elongation initiation factor 4E (eIF4E) independent mTOR....

Abstract Skeletal muscle regeneration involves a signaling network that regulates the proliferation, differentiation, and fusion of precursor cells to injured myofibers. IRE1α, one arms unfolded protein response, cellular proteostasis in response ER stress. Here, we demonstrate inducible deletion IRE1α satellite mice impairs skeletal through inhibiting myoblast fusion. Knockdown or its downstream target, X-box 1 (XBP1), also inhibits during myogenesis. Transcriptome analysis revealed...

Abstract Transcriptional determinants in the skeletal muscle that govern exercise capacity, while poorly defined, could provide molecular insights into how improves fitness. Here, we have elucidated role of nuclear receptors, estrogen‐related receptor alpha and gamma (ERRα/γ) regulating myofibrillar composition, contractility, capacity muscle. We used muscle‐specific single or double (DKO) ERRα/γ knockout mice to investigate effect deletion on parameters. Individual did not a significant...

Selenoprotein N-related myopathy (SEPN1-RM) is a genetic disease that causes muscle weakness and respiratory failure. Germani et al.1Germani S. Ho A.T.V. Cherubini A. Varone E. Chernorudskiy Renna G.M. Fumagalli Gobbi M. Lucchetti J. Bolis al.SEPN1-related depends on the oxidoreductase ERO1 alpha druggable with chemical chaperone TUDCA.Cell Rep. Med. 2024; 5: 101439https://doi.org/10.1016/j.xcrm.2024.101439Google Scholar demonstrate diaphragm in SEPN1-RM prevented by inhibition of ER stress...

Triple negative breast cancer (TNBC) tends to form aggressive tumors associated with high mortality and morbidity which urge the need for development of new therapeutic strategies. Recently, normal metabolite Methylglyoxal (MG) has been documented its anti‐proliferative activity against human cancer. However, mode action MG TNBC remains open question. In our study, we investigated anticancer in MDA MB 231 4T1 cell lines elucidated underlying mechanisms. dose‐dependently caused death, induced...

Skeletal muscle regeneration is regulated by coordinated activation of multiple signaling pathways. The unfolded protein response (UPR) a major mechanism that detects and alleviates protein-folding stresses in the endoplasmic reticulum. However, role individual arms UPR skeletal remain less understood. In present study, we demonstrate IRE1α (also known as ERN1) its downstream target, XBP1, are activated mice upon injury. Myofiber-specific ablation or XBP1 diminishes accompanied with reduced...

Skeletal muscle atrophy is a debilitating complication of many chronic disease states and disuse conditions including denervation. However, molecular signaling mechanisms wasting remain less understood. Here, we demonstrate that the levels several toll-like receptors (TLRs) their downstream adaptor, myeloid differentiation primary response 88 (MyD88), are induced in skeletal mice to sciatic nerve Muscle-specific ablation MyD88 mitigates denervation-induced mice. Targeted suppresses...

Skeletal muscle regeneration involves coordinated activation of an array signaling pathways. Fibroblast growth factor-inducible 14 (Fn14) is a bona fide receptor for the TWEAK cytokine. Levels Fn14 are increased in skeletal mice after injury. However, cell-autonomous role remains unknown. Here, we demonstrate that global deletion attenuates regeneration. Conditional ablation myoblasts but not differentiated myofibers inhibits promotes myoblast fusion without affecting levels myogenic...

The normal metabolite methylglyoxal (MG) specifically kills cancer cells by inhibiting glycolysis and mitochondrial respiration without much adverse effect upon cells. Though the anticancer property of MG is well documented, its gradual enzymatic degradation in vivo has prompted interest developing a nanoparticulate drug delivery system to protect it also enhance efficacy.MG-conjugated chitosan nanoparticles (Nano-MG) were prepared conjugating carbonyl group with amino polymer (Schiff's base...

Skeletal muscle atrophy is debilitating consequence of a large number chronic disease states, aging, and disuse conditions. mass regulated through coordinated activation signaling cascades. Transforming growth factor-β activated kinase 1 (TAK1) central that mediates the multiple pathways in response to various factors, cytokines, microbial products. Accumulating evidence suggests TAK1 promotes skeletal essential for maintenance adults. Targeted inactivation leads severe wasting kyphosis...

Bromodomains are evolutionarily conserved reader modules that recognize acetylated lysine residues on the histone tails to facilitate gene transcription. The bromodomain and PHD finger containing protein 3 (BRPF3) is a scaffolding forms tetrameric complex with HBO1 acetyltransferase (HAT) two other subunits, which known regulate HAT activity substrate specificity. However, its molecular mechanism, ligands, biological functions remain unknown. Herein, we identify mono- (H4K5ac) di-...

Skeletal muscle atrophy is a prevalent complication in multiple chronic diseases and disuse conditions. Fibroblast growth factor-inducible 14 (Fn14) member of the TNF receptor superfamily bona fide TWEAK cytokine. Accumulating evidence suggests that Fn14 levels are increased catabolic conditions as well during exercise. However, role regulation skeletal mass function remains poorly understood. In this study, through generation novel muscle-specific Fn14-knockout mice, we have investigated...

TRIM24 is a multi-functional chromatin reader, and it binds to the estrogen receptor activate estrogen-dependent target genes associated with tumor development. known ubiquitinate p53 via an N-terminal RING domain specific combinatorial histone signature of H3K4me0/H3K23ac its C-terminal plant homeodomain (PHD) bromodomain (Bromo). Aberrant expression positively correlates H3K23ac levels, high levels both predict poor survival breast cancer patients. Little has been explored about acetylated...

The material used in the present study is of diverse nature and can be breeding programme for development improved genotypes cucumber (Cucumis sativus L.). unique accessions identified this useful as genetic stocks. superior fruit trait variability combined with disease resistance may assist breeders identifying populations desired traits inclusion crop improvement programme.

HBO1 [HAT bound to the origin recognition complex (ORC)], a member of MYST family histone acetyltransferases (HATs), was initially identified as binding partner ORC that acetylates free H3, H4, and nucleosomal H3. It functions quaternary with BRPF (BRPF1/2/3) scaffolding protein two accessory proteins, ING4/5 Eaf6. Interaction BRPF2 has been shown be important for regulating H3K14 acetylation during embryonic development. However, how directs HAT chromatin regulate its activity toward...

Therapy resistance and relapse is the worst prognostic outcome of cancer attributed to presence cancer stem cells in tumor mass. Cancer stem survive cytotoxic effects commonly used chemotherapeutic drugs radiation which targets eradicates non reducing bulk but unable to stop recurrence. re-initiate evolutionary conserved embryonic signaling pathways such as Wnt, Hedgehog Notch thereby endowing themselves with properties pluripotency, self renewal and maintenance, activate DNA damage...

Background: A target protein-based affinity extraction LC–MS/MS method was developed to enable plasma level determination following ultralow dosing (0.1–3 µg/kg) of an inhibitor apoptosis proteins molecule. Methodology & results: Affinity (AE) utilizing immobilized protein BIR2/BIR3 used selectively capture the molecule from dog and removal background matrix components. Pretreatment samples using precipitation found provide additional sensitivity gain. LLOQ 7.8 pM achieved by combining with...

ABSTRACT Cachexia is an involuntary loss of body weight mostly due to skeletal muscle wasting. The proinflammatory cytokine TWEAK and its receptor Fn14 constitute a major signaling system that regulates mass in diverse conditions. However, the role TWEAK/Fn14 regulation during cancer-induced cachexia remains poorly understood. In this study, we demonstrate levels Fn14, but not TWEAK, are induced multiple mouse models cancer cachexia. Targeted deletion inhibits wasting gene expression...