Discovery of pyridazinone derivatives bearing tetrahydroimidazo[1,2-a]pyrazine scaffold as potent inhibitors of transient receptor potential canonical 5 to ameliorate hypertension-induced renal injury in rats

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 275, P. 116565 - 116565

Published: June 4, 2024

Language: Английский

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Are Aminoglycoside Antibiotics TRPing Your Metabolic Switches?

Cells, Journal Year: 2024, Volume and Issue: 13(15), P. 1273 - 1273

Published: July 29, 2024

Transient receptor potential (TRP) channels are broadly implicated in the developmental programs of most tissues. Amongst these tissues, skeletal muscle and adipose noteworthy for being essential establishing systemic metabolic balance. TRP respond to environmental stimuli by supplying intracellular calcium that instigates enzymatic cascades consequence often impinge on mitochondrial function biogenesis. Critically, aminoglycoside antibiotics (AGAs) have been shown block capacity conduct entry into cell response a wide range biophysical nature, including mechanical, electromagnetic, thermal, chemical. Paradoxically, vitro paradigms commonly used understand organismal development may led astray conventional use streptomycin, an AGA, help prevent bacterial contamination. Accordingly, streptomycin has disrupt both vivo myogenesis, as well phenotypic switch white beige thermogenic status. In vivo, TRP-mediated calcium-dependent exercise adaptations importance metabolism. Alternatively, also curb detrimental levels leakage dystrophic through aberrantly gated TRPC1 be involved etiology X-linked muscular dystrophies. susceptible AGA antagonism critically modulating tissues that, if administered behaving animals, translate systemwide disruption. Regenerative medicine clinical communities need made aware this caveat usage seek viable alternatives, contamination or infection paradigms, respectively.

Language: Английский

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TRPC absence induces pro-inflammatory macrophage polarization to promote obesity and exacerbate colorectal cancer

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 21, 2024

During the past half-century, although numerous interventions for obesity have arisen, condition’s prevalence has relentlessly escalated annually. Obesity represents a substantial public health challenge, especially due to its robust correlation with co-morbidities, such as colorectal cancer (CRC), which often thrives in an inflammatory tumor milieu. Of note, individuals commonly present calcium and vitamin D insufficiencies. Transient receptor potential canonical (TRPC) channels, subclass within broader TRP family, function critical transporters calcium-mediated signaling pathways. However, exact role of TRPC channels both CRC pathogenesis remains poorly understood. This study set out elucidate part played by development using mouse model lacking all seven proteins (TRPC HeptaKO mice). Relative wild-type counterparts, mice manifested severe obesity, evidenced significantly heightened body weights, augmented weights epididymal white adipose tissue (eWAT) inguinal (iWAT), increased hepatic lipid deposition, raised serum levels total cholesterol (T-CHO) low-density lipoprotein (LDL-C). Moreover, deficiency was accompanied decrease thermogenic molecules like PGC1-α UCP1, alongside upsurge factors tissue. Mechanistically, it revealed that pro-inflammatory originating from macrophages triggered accumulation exacerbated obesity-related phenotypes. Intriguingly, considering well-established connection between disrupted gut microbiota balance, changes composition were detected mice, contributing development. provides valuable insights into underlying mechanisms related complication, CRC. Our findings offer theoretical foundation prevention adverse effects associated inhibitors, potentially leading new therapeutic strategies prevention.

Language: Английский

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TRPC3: how current mechanistic understanding provides a basis for therapeutic targeting

Expert Opinion on Therapeutic Targets, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 9

Published: Nov. 15, 2024

Intensive and detailed investigations of the molecular function cellular role mammalian transient receptor potential canonical (TRPC) channels started back in early 90

Language: Английский

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SIRT-2 inhibition by AK-7 orchestrates fibrotic cascades in airways through neuroimmune interaction via TRPA1, TRPM8 and TGF-β signalling

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 116689 - 116689

Published: Nov. 1, 2024

Language: Английский

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Pyr3 inhibits cell viability and PKCα activity to suppress migration in human bladder cancer cells

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 177235 - 177235

Published: Dec. 1, 2024

Language: Английский

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