Anti-ACE monoclonal antibody, clone i2H5

beta-thalassemia is a hereditary disorder caused by defective production of beta-globin chains of hemoglobin (Hb) that leads to an increased alpha/beta globins ratio with subsequent free alpha-globins. Alpha globin excess causes oxidative stress, red blood cells membrane damage, premature death of late-stage erythroid precursors, resulting in ineffective erythropoiesis. The transforming growth factor beta (TGF-beta) superfamily signaling acts on biological processes, such as cell quiescence, apoptosis, proliferation, differentiation, and migration, and plays an essential role in regulating the hematopoiesis. This pathway can lose its physiologic regulation in pathologic conditions, leading to anemia and ineffective erythropoiesis. Activin receptor-ligand trap molecules such as Sotatercept and Luspatercept downregulate the TGF-beta pathway, thus inhibiting the Smad2/3 cascade and alleviating anemia in patients with beta-thalassemia and myelodysplastic syndromes. In this review, we describe in extenso the TGF-beta pathway, as well as the molecular and biological basis of activin receptors ligand traps, focusing on their role in various beta-thalassemia experimental models. The most recent results from clinical trials on sotatercept and luspatercept will also be reviewed.

Exposure to insecticides containing organophosphate (OP) and neonicotinoid (NEO) compounds has been associated with adverse reproductive health outcomes. This study characterized and identified predictors of exposure to OP and NEO among 100 reproductive-age farmworkers from two intensive farming areas in Chiang Mai Province, Thailand, including 50 each from the Fang (FA) and Chom Thong (CT) districts. OP exposure was determined by measuring the urinary concentrations of six dialkylphosphates (DAPs), whereas NEO exposure was determined by measuring the urinary concentrations of NEO compounds and their metabolites (NEO/m). The most frequently detected OPs were diethylphosphate (DEP) and diethylthiophosphate (DETP), with DETP having the highest geometric mean (GM) concentration, 8.9 mu g/g-creatinine. The most frequently detected NEO/m were N-desmethyl-acetamiprid (N-dm-ACE), imidacloprid (IMI), and thiamethoxam (THX), with IMI having the highest GM concentration, 8.7 mu g/g-creatinine. Consumption of well water was the predominant determinant of OP and NEO exposure in this population. In addition to encouraging workers to use personal protective equipment, exposure of farmworkers to these compounds may be reduced by nation-wide monitoring agricultural insecticides and other pesticides in community drinking water resources.