Preclinical and Clinical Pharmacokinetics of JNJ-75220795, an siRNA Therapeutic Targeting PNPLA3, for Metabolic Dysfunction-Associated Steatohepatitis.

JNJ-75220795 or ARO-PNPLA3 is an investigational small interfering ribonucleic acid agent conjugated with N-acetyl-d-galactosamine that targets the PNPLA3 gene, currently being developed for metabolic dysfunction-associated steatohepatitis (MASH). This study evaluated the pharmacokinetics (PK) profile of single subcutaneous doses of JNJ-75220795 in preclinical species as well as in human subjects with homozygous or heterozygous PNPLA3 I148M mutation in two phase 1 studies-a first-in-human study in the United States and a first-in-Japanese study in Japan. Preclinical PK in rats and non-human primates (NHP) showed a rapid systemic absorption and elimination following single subcutaneous doses.

Ancient evolutionary origins of hepatitis E virus in rodents.

Hepatitis E virus (HEV; family ) infections cause >40,000 human deaths annually. Zoonotic infections predominantly originate from ungulates and occasionally from rats, highlighting the zoonotic potential of rodent-associated hepeviruses. We conducted host genomic data mining and uncovered two genetically divergent rodent-associated hepeviruses, and two bat-associated hepeviruses genetically related to known bat-associated strains.

[Modern biochemical markers of acute mesenteric ischemia].

Objective: To analyze modern literature data on biochemical markers of critical mesenteric ischemia.

Material And Methods: We analyzed the most promising, highly specific and sensitive biochemical markers of total and segmental intestinal damage following acute mesenteric ischemia. Analysis included domestic and foreign literature data between 2015 and 2023.