Synthesis, evaluation and mechanistic insights of novel IMPDH inhibitors targeting ESKAPEE bacteria.

Antimicrobial resistance poses a significant threat to global health, necessitating the development of novel therapeutic agents with unique mechanisms of action. Inosine 5'-monophosphate dehydrogenase (IMPDH), an essential enzyme in guanine nucleotide biosynthesis, is a promising target for the discovery of new antimicrobial agents. High-throughput screening studies have previously identified several urea-based leads as potential inhibitors, although many of these are characterised by reduced chemical stability.

A journey into the regulatory secrets of the purine nucleotide biosynthesis.

purine nucleotide biosynthesis (DNPNB) consists of sequential reactions that are majorly conserved in living organisms. Several regulation events take place to maintain physiological concentrations of adenylate and guanylate nucleotides in cells and to fine-tune the production of purine nucleotides in response to changing cellular demands. Recent years have seen a renewed interest in the DNPNB enzymes, with some being highlighted as promising targets for therapeutic molecules.

Insight into the role of the Bateman domain at the molecular and physiological levels through engineered IMP dehydrogenases.

Inosine 5'-monophosphate (IMP) dehydrogenase (IMPDH) is an ubiquitous enzyme that catalyzes the NAD -dependent oxidation of inosine 5'-monophosphate into xanthosine 5'-monophosphate. This enzyme is formed of two distinct domains, a core domain where the catalytic reaction occurs, and a less-conserved Bateman domain. Our previous studies gave rise to the classification of bacterial IMPDHs into two classes, according to their oligomeric and kinetic properties.

Challenges Facing Viral Hepatitis C Elimination in Lebanon.

Hepatitis C is a hepatotropic virus that causes progressive liver inflammation, eventually leading to cirrhosis and hepatocellular carcinoma if left untreated. All infected patients can achieve a cure if treated early. Unfortunately, many patients remain asymptomatic and tend to present late with hepatic complications.

Interaction network among de novo purine nucleotide biosynthesis enzymes in Escherichia coli.

In human cells, de novo purine nucleotide biosynthesis is known to be regulated through the formation of a metabolon called purinosome. Here, we employed a bacterial two-hybrid approach to characterize the protein-protein interactions network among the corresponding enzymes of Escherichia coli. Our study revealed a dense network of binary interactions that connect most purine nucleotide biosynthesis enzymes.

Improved Survival for Patients with Systemic Sclerosis-associated Pulmonary Arterial Hypertension: The Johns Hopkins Registry.

To date, it remains unclear whether recent changes in the management of patients with systemic sclerosis-associated pulmonary hypertension (SSc-PH) have improved survival. To describe a cohort of patients with SSc-PH and compare their characteristics and survival between the last two decades. Patients with SSc-PH prospectively enrolled in the Johns Hopkins Pulmonary Hypertension Center Registry were grouped into two cohorts based on the date of diagnostic right heart catheterization: cohort A included patients whose disease was diagnosed between 1999 and 2010, and cohort B included those whose disease was diagnosed between 2010 and 2021.

Serum Cadmium Levels and Risk of Metabolic Syndrome: A Cross-Sectional Study.

The increase in the prevalence of metabolic disorders globally is becoming a public health concern. Previous studies have reported an association between environmental exposures to hazardous substances, including various heavy metals, and the risk for metabolic syndrome. However, reports on the contributions of cadmium (Cd) to the risk for obesity and diabetes remain inconsistent.