TFEB triggers a matrix degradation and invasion program in triple-negative breast cancer cells upon mTORC1 repression.

The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently hyperactivated in triple-negative breast cancers (TNBCs) associated with poor prognosis and is a therapeutic target in breast cancer management. Here, we describe the effects of repression of mTOR-containing complex 1 (mTORC1) through knockdown of several key mTORC1 components or with mTOR inhibitors used in cancer therapy. mTORC1 repression results in an ∼10-fold increase in extracellular matrix proteolytic degradation.

Correlating symptom severity index, clinical diagnostic criteria of CTS-6 and timed Phalen's test in clinical evaluation of carpal tunnel syndrome.

Background: Carpal Tunnel Syndrome (CTS) poses significant diagnostic challenges, especially in resource-limited settings. Reliable tools such as the 6-item Symptom Severity Index, Timed Phalen's Test (TPT) and CTS-6 are promising but under investigated. Correlation between these tools and symptom severity remains underexplored.

Integrating traditional QSAR and read-across-based regression models for predicting potential anti-leishmanial azole compounds.

Leishmaniasis, a neglected tropical disease caused by various Leishmania species, poses a significant global health challenge, especially in resource-limited regions. Visceral Leishmaniasis (VL) stands out among its severe manifestations, and current drug therapies have limitations, necessitating the exploration of new, cost-effective treatments. This study utilized a comprehensive computational workflow, integrating traditional 2D-QSAR, q-RASAR, and molecular docking to identify novel anti-leishmanial compounds, with a focus on Glycyl-tRNA Synthetase (LdGlyRS) as a promising drug target.

Stem cell factor-mediated upregulation of SIRT1 protects melanin-deprived keratinocytes against UV-induced DNA damage in individuals with vitiligo.

Despite the loss of melanocytes, individuals with vitiligo have a significantly lower risk of developing skin malignancies compared to ethnicity-matched controls. The study investigated the molecular mechanisms that protect skin cells (keratinocytes) from UV-B-induced DNA damage in individuals with vitiligo. The study found that upregulation of stem cell factor (SCF) signaling significantly reduced γ-H2AX positivity and cyclobutane pyrimidine dimer formation and improved mitochondrial health (elongated mitochondria, reduced reactive oxygen species [ROS] and lipid peroxidation) in keratinocytes upon UV-B exposure.

Mitochondrial calcium uptake orchestrates vertebrate pigmentation via transcriptional regulation of keratin filaments.

Mitochondria regulate several physiological functions through mitochondrial Ca2+ dynamics. However, role of mitochondrial Ca2+ signaling in melanosome biology remains unknown. Here, we show that pigmentation requires mitochondrial Ca2+ uptake.