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| http://dx.doi.org/10.14309/crj.0000000000001117 | DOI Listing |
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Population genetics and molecular xenomonitoring of Biomphalaria freshwater snails along the southern shoreline of Lake Malawi, Malawi.
Parasit Vectors
December 2024
Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Background: Intestinal schistosomiasis was confirmed endemic in Mangochi District, Malawi, in May of 2018 following an unexpected encounter with discreet populations of Biomphalaria spp. freshwater snails during routine malacological surveillance activities. Since then, only limited malacological surveillance of Biomphalaria has been carried out, and so the distribution of Biomphalaria populations in this area is currently unclear.
View Article and Find Full Text PDFSingle-Dose Drug Development Candidate for Schistosomiasis.
ACS Infect Dis
November 2024
College of Pharmacy, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska 986125, United States.
Aryl hydantoins were identified in the early 1980s as a promising antischistosomal chemotype. However, as exemplified by Ro 13-3978, this compound series produced antiandrogenic side effects on the host, a not unexpected outcome given their structural similarity to the antiandrogenic drug nilutamide. The two key advances in our optimization of Ro 13-3978 were swapping the aryl trifluoromethyl substituent with a difluoroethyl to abolish antiandrogenic effects and replacing the hydrogen atoms of the -dimethyl substructure with deuterium atoms to increase metabolic stability.
View Article and Find Full Text PDFUnexpected outcome of dyspeptic syndrome.
Rev Esp Enferm Dig
December 2024
Gastroenterology, Hospital Central de Maputo.
A 57-year-old black male patient was admitted with flatulence and post-prandial fullness a month ago. No other gastrointestinal complaints. He had history of arterial hypertension, medicated with nifedipine 30mg/day and hydrochlorthiazide 50mg/day, and had been diagnosed and treated for malaria a week before admission.
View Article and Find Full Text PDFThe "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.
J Med Chem
September 2024
Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Pyridine nucleotide-disulfide oxidoreductases are underexplored as drug targets, and thioredoxin reductases (TrxRs) stand out as compelling pharmacological targets. Selective TrxR inhibition is challenging primarily due to the reliance on covalent inhibition strategies. Recent studies identified a regulatory and druggable pocket in thioredoxin glutathione reductase (TGR), a TrxR-like enzyme, and an established drug target for schistosomiasis.
View Article and Find Full Text PDFEndogenous PGD2 acting on DP2 receptor counter regulates Schistosoma mansoni infection-driven hepatic granulomatous fibrosis.
PLoS Pathog
August 2024
Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Identifying new molecular therapies targeted at the severe hepatic fibrosis associated with the granulomatous immune response to Schistosoma mansoni infection is essential to reduce fibrosis-related morbidity/mortality in schistosomiasis. In vitro cell activation studies suggested the lipid molecule prostaglandin D2 (PGD2) as a potential pro-fibrotic candidate in schistosomal context, although corroboratory in vivo evidence is still lacking. Here, to investigate the role of PGD2 and its cognate receptor DP2 in vivo, impairment of PGD2 synthesis by HQL-79 (an inhibitor of the H-PGD synthase) or DP2 receptor inhibition by CAY10471 (a selective DP2 antagonist) were used against the fibrotic response of hepatic eosinophilic granulomas of S.
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