Age-Related ECM Stiffness Mediates TRAIL Activation in Muscle Stem Cell Differentiation.

The stiffening of the extracellular matrix (ECM) with age hinders muscle regeneration by causing intrinsic muscle stem cell (MuSC) dysfunction through a poorly understood mechanism. Here, the study aims to study those age-related molecular changes in the differentiation of MuSCs due to age and/or stiffness. Hence, young and aged MuSCs are seeded onto substrates engineered to mimic a soft and stiff ECM microenvironment to study those molecular changes using single-cell RNA sequencing (scRNA).

New antiparasitic flexible triaryl diamidines, their prodrugs and aza analogues: Synthesis, in vitro and in vivo biological evaluation, and molecular modelling studies.

Dicationic diamidines have been well established as potent antiparasitic agents with proven activity against tropical diseases like trypanosomiasis and malaria. This work presents the synthesis of new mono and diflexible triaryl amidines (6a-c, 13a,b and 17), their aza analogues (23 and 27) and respective methoxyamidine prodrugs (5, 7, 12a,b, 22 and 26). All diamidines were assessed in vitro against Trypanosoma brucei rhodesiense (T.

Targeting homologous recombination (HR) repair mechanism for cancer treatment: discovery of new potential UCHL-3 inhibitors virtual screening, molecular dynamics and binding mode analysis.

UCHL3 (ubiquitin C-terminal hydrolase-L3) is a de-ubiquitinating enzyme involved in the homologous recombination repair mechanism of double-strand breaks (DBS) of the DNA. Multiple studies indicated that UCHL3 inhibitors could be used in combination therapy with high therapeutic efficacy against cancer thus highlighting the validity of directing research against UCHL3 as a druggable target in oncology. In this study, a combination of virtual screening methods was utilized to identify new potential UCHL3 inhibitors.

Triaryl dicationic DNA minor-groove binders with antioxidant activity display cytotoxicity and induce apoptosis in breast cancer.

Despite advances in cancer treatment modalities, DNA still stands as one of the targets for anticancer agents. DNA minor groove binders (MGBs) represent an important investigational chemotherapeutic class with promising cytotoxic capacity. Herein this study reports the potent cytotoxic effect of a series of repurposed flexible bis-imidamides 1-4, triaryl bis-guanidine 5 and bis-N-substituted guanidines 6,7 having a 1,4-diphenoxybenzene scaffold backbone on MCF-7 and MDA-MB-231 breast cancer cell lines.