Nicotinamide mononucleotide supplementation rescues mitochondrial and energy metabolism functions and ameliorates inflammatory states in the ovaries of aging mice.

Noninvasive pharmacological strategies like nicotinamide mononucleotide (NMN) supplementation can effectively address age-related ovarian infertility by maintaining or enhancing oocyte quality and quantity. This study revealed that ovarian nicotinamide adenine dinucleotide levels decline with age, but NMN administration significantly restores these levels, preventing ovarian atrophy and enhancing the quality and quantity of ovulated oocytes. Improvements in serum hormone secretion and antioxidant factors, along with decreased expression of proinflammatory factors, were observed.

Oxidation-responsive G-quadruplex ligand for selective inhibition of the proliferation of tumour cells.

Tumour cells show a higher level of reactive oxygen species (ROS) than normal cells. On the basis of this difference, we designed an oxidation-responsive G-quadruplex proligand PDS-B by installing borolanylbenzyls on a well-known pyridostatin (PDS) ligand PDS-S to response high level ROS in tumour cells. The rapid oxidative degradation of the proligand to its active form PDS-S in the presence of HO confirms the oxidation-responsive design.

Synergistic effect of naphthalenediimide and squaraine ligand targeting G-quadruplex DNA in cancer cells.

Targeting and stabilizing nonclassical DNA G-quadruplexes (G4s) with a ligand to inhibit cell proliferation is a very promising approach for cancer treatment. Here, we demonstrate that the combination of a naphthalenediimide (NDI) ligand and a squaraine ligand significantly improves the anticancer activity of either ligand alone. The NDI ligand binds the 5'-terminal of hybrid-type G4s and induces the topological conversion from a metastable hybrid to a stable parallel conformation, which allows the end-stacking of the squaraine ligand on the 3'-terminal of the resultant parallel-type G4 structure.

A naphthyridine-indole ligand for selective stabilization of G-quadruplexes and conformational conversion of hybrid topology.

The development of ligands to stabilize G-quadruplexes (G4s) or induce G4s to transition from metastable topology to stable topology is a potential strategy for inhibiting cancer cell proliferation. In this study, a novel G-quadruplex (G4) ligand based on a naphthyridine scaffold with two indole pendants, L5-DA, is reported to convert hybrid to the parallel topology. Circular dichroism (CD) and fluorescence spectroscopies were used to investigate the interactions between L5-DA and G4s.

Hydrogen-bond-driven dimers of naphthyridine derivatives for selective identification of DNA G-quadruplexes.

G-quadruplex (GQ) ligands as potential anti-cancer drugs have received extensive attention. Large aromatic systems are usually considered in the design of the ligands to improve the binding with GQs, which are typically constructed by the combination of small modules with covalent bonds. In this study, we presented a non-covalent bond approach to construct GQ ligands with an extended planar structure.

Topological conversion of human telomeric G-quadruplexes from hybrid to parallel form induced by naphthalene diimide ligands.

G-quadruplexes (GQs) have become promising anti-cancer therapeutic targets, which are formed by the folding of a guanine-rich repeat DNA/RNA sequence at human telomeres or oncogene promoters. Polymorphism has been observed for the folding topologies of intramolecular GQs. Here we report the topological conversion of human telomeric GQ induced by naphthalene diimide (NDI) ligands in K solution.

Urothelial Carcinoma Detection Based on Copy Number Profiles of Urinary Cell-Free DNA by Shallow Whole-Genome Sequencing.

Background: Current noninvasive assays for urothelial carcinoma (UC) lack clinical sensitivity and specificity. Given the utility of plasma cell-free DNA (cfDNA) biomarkers, the development of urinary cfDNA biomarkers may improve the diagnostic sensitivity.

Methods: We assessed copy number alterations (CNAs) by shallow genome-wide sequencing of urinary cfDNA in 95 cancer-free individuals and 65 patients with UC, 58 with kidney cancer, and 45 with prostate cancer.

In vitro Characterization of the Rapid Cytotoxicity of Anticancer Peptide HPRP-A2 through Membrane Destruction and Intracellular Mechanism against Gastric Cancer Cell Lines.

In this study, HPRP-A2, a synthetic 15-mer cationic peptides with all D-amino acids, effectively inhibited the survival of gastric cell lines in a dose-dependent manner. Gastric tumor cells killing by HPRP-A2 involves a rapid collapse of the membrane integrity and intracellular pathways. Propidium iodide (PI) and lactate dehydrogenase (LDH) assays demonstrated that one-hour treatment with HPRP-A2 led to membrane permeability changes of BGC-823 cells in a dose-dependent manner.

TAT Modification of Alpha-Helical Anticancer Peptides to Improve Specificity and Efficacy.

HPRP-A1 is an amphipathic α-helical anticancer peptide (ACP) derived from the N-terminus of ribosomal protein L1 (RpL1) of Helicobacter pylori. In our previously study, HPRP-A1 has been reported that induced HeLa cell apoptosis in a caspase-dependent approach and involved both by the death receptor 'extrinsic' pathway and the mitochondria 'intrinsic' pathway. Here we report the construction of a new hybrid peptide, HPRP-A1-TAT, comprising the cell-permeating peptide TAT linked to the C-terminus of HPRP-A1.

Alpha-helical cationic anticancer peptides: a promising candidate for novel anticancer drugs.

Cancer has become a serious concern in public health. Harmful side effects and multidrug resistance of traditional chemotherapy have prompted urgent needs for novel anticancer drugs or therapeutic approaches. Anticancer peptides (ACPs) have become promising molecules for novel anticancer agents because of their unique mechanism and several extraordinary properties.

Identification and functional analysis of mitogen-activated protein kinase kinase kinase (MAPKKK) genes in canola (Brassica napus L.).

Mitogen-activated protein kinase (MAPK) signalling cascades, consisting of three types of reversibly phosphorylated kinases (MAPKKK, MAPKK, and MAPK), are involved in important processes including plant immunity and hormone responses. The MAPKKKs comprise the largest family in the MAPK cascades, yet only a few of these genes have been associated with physiological functions, even in the model plant Arabidopsis thaliana. Canola (Brassica napus L.