benzofurans and Muscular-Atrophy

The in vitro capacity of

Topics: Animals; Benzofurans; Complex Mixtures; Dexamethasone; Dioxins; Mice; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Phaeophyceae; RNA, Messenger

Topics: Animals; Benzofurans; Diet, High-Fat; Dietary Fats; Gene Expression Regulation; Lipid Droplets; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Perilipin-1; Phaeophyceae; PPAR alpha

To identify natural inhibitors against MCT8 for Allan-Herndon-Dudley Syndrome.. Monocarboxylate Transporter 8 (MCT8) is a Thyroid Hormone (TH) transporter which is highly expressed in the liver and brain. Mutations in the MCT8 gene (SLC16A2) cause a syndrome of psychomotor retardation in humans, known as Allan-Herndon-Dudley syndrome (AHDS). Currently, no treatment is available for AHDS. Therefore, there is a need to discover new inhibitors of MCT8 for treating AHDS.. Considering the importance of natural compounds in drug discovery, this study aimed to identify potential natural inhibitors against MCT8.. As Protein-ligand interactions play a key role in structure based drug design, this study screened 24 natural kinase inhibitors and investigated their binding affinity against MCT8 by using molecular docking. The modelled 3D structure of MCT8 docked with 24 compounds using PyRX through Autodock Vina. Drug-likeness studies were made using Swiss ADME and Lipinski's rule of five was performed. Triac, desipramine and silychristin were used as the positive controls. Binding energies of the selected compounds were compared with that of positive controls.. The results showed that emodin exhibited best binding energy of -8.6 kcal/mol followed by helenaquinol, cercosporamide and resveratrol. Moreover, it was observed that emodin and helenaquinol exhibit higher binding energy than the positive controls. Cercosporamide and resveratrol exhibited higher binding energy than triac and desipramine and showed the binding energy similar to silychristin.. This study reveals that these compounds could be promising candidates for further evaluation for AHDS prevention.

Topics: Benzofurans; Biological Transport; Drug Discovery; Emodin; Humans; Mental Retardation, X-Linked; Molecular Docking Simulation; Monocarboxylic Acid Transporters; Muscle Hypotonia; Muscular Atrophy; Mutation; Phytochemicals; Protein Kinase Inhibitors; Resveratrol; Symporters; Thyroid Hormones

The role and significance of liver-derived cytokines in cancer-associated cachexia syndrome remain elusive. Here we report that combinatorial counterbalances of the leptin and Igf1 signaling pathways in hepatocellular carcinoma (HCC) models significantly relieves cachexia. Double transgenic zebrafish models of HCC that stably displayed focal lesions, anorexia, and wasting of adipose and muscle tissues were first generated. Knockout of lepr or mc4r from these zebrafish partially restored appetite and exerted moderate or no effect on tissue wasting. However, genetic replenishment of Igf1 in a lepr-mutant background effectively relieved the cachexia-like phenotype without affecting tumor growth. Similarly, administration of napabucasin, a Stat3/Socs3 inhibitor, on the zebrafish HCC model, mammalian cell lines with exogenous IGF1, and two mouse xenograft models restored insulin sensitivity and rescued the wasting of nontumor tissues. Together, these results describe the synergistic impact of leptin and Igf1 normalization in treating certain HCC-associated cachexia as a practical strategy. SIGNIFICANCE: Disruption of leptin signaling with normalized Igf1 expression significantly rescues anorexia, muscle wasting, and adipose wasting in Ras- and Myc-driven zebrafish models of HCC.

Topics: 3T3-L1 Cells; Adipose Tissue; Animals; Animals, Genetically Modified; Benzofurans; Cachexia; Carcinoma, Hepatocellular; Cells, Cultured; Cytokines; Disease Models, Animal; Drug Synergism; HEK293 Cells; Hep G2 Cells; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Liver; Liver Neoplasms; Mice; Muscular Atrophy; Naphthoquinones; Receptors, Leptin; Signal Transduction; Wasting Syndrome; Xenograft Model Antitumor Assays; Zebrafish

Topics: Animals; Benzofurans; Dexamethasone; Glucocorticoids; Inflammasomes; Male; Mice; Mice, Inbred ICR; Muscular Atrophy; NLR Family, Pyrin Domain-Containing 3 Protein; Plant Extracts; Pyroptosis

Muscle biopsy has long been expected to be replaced by noninvasive biomarkers with diagnostic value and prognostic applications for muscle atrophy. Growing evidence suggests that circulating microRNAs (miRNAs) could act as biomarkers for numerous pathophysiological statuses. In the present study, our results showed that the serum levels of six muscle-specific miRNAs (miR-1/23a/133/206/208b/499) were all elevated in unloading induced mice. The medium levels of these six muscle-specific miRNAs were all elevated in starvation induced atrophic C2C12 myotubes. Moreover, the serum levels of miR-23a/206/499 were induced in participants after 45 days of head-down bed rest (HDBR). The levels of miR-23a/206/499 were positively correlated with the ratio of soleus volume loss in HDBR participants, indicating that they might represent the process of muscle loss. In conclusion, our results demonstrated that circulating miRNAs could serve as useful biochemical and molecular indicators for muscle atrophy diagnosis and disease progression.

Topics: Adult; Animals; Bed Rest; Benzofurans; Biomarkers; Cells, Cultured; Humans; Male; Mice; MicroRNAs; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Prognosis; Quinolines