👤 Jeffrey M Grabowski

Coronary artery disease (CAD), which is the manifestation of atherosclerosis in coronary arteries, is the most common single cause of death and is responsible for disabilities of millions of people worldwide. Despite numerous dedicated clinical studies and an enormous effort to develop diagnostic and therapeutic methods, coronary atherosclerosis remains one of the most serious medical problems of the modern world. Hence, new markers are still being sought to identify and manage CAD optimally. Trying to face this problem, we have raised the question of the most predominant gastrointestinal hormones; glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), mainly involved in carbohydrates disorders, could be also used as new markers of incidence, clinical course, and recurrence of CAD and are related to extent and severity of atherosclerosis and myocardial ischemia. We describe GIP and GLP-1 as expressed in many animal and human tissues, known to be connected to inflammation and related to enormous noncardiac and cardiovascular (CV) diseases. In animals, GIP and GLP-1 improve endothelial function and lead to reduced atherosclerotic plaque macrophage infiltration and stabilize atherosclerotic lesions by directly blocking monocyte migration. Moreover, in humans, GIPR activation induces the pro-atherosclerotic factors ET-1 (endothelin-1) and OPN (osteopontin) but also has anti-atherosclerotic effects through secretion of NO (nitric oxide). Furthermore, four large clinical trials showed a significant reduction in composite of CV death, MI, and stroke in long-term follow-up using GLP-1 analogs for DM 2 patients: liraglutide in LEADER, semaglutide in SUSTAIN-6, dulaglutide in REWIND and albiglutide in HARMONY. However, very little is known about GIP metabolism in the acute phase of myocardial ischemia or for stable patients with CAD, which constitutes a direction for future research. This review aims to comprehensively discuss the impact of GIP and GLP-1 on atherosclerosis and CAD and its potential therapeutic implications. Show less

From 1983, standardized therapeutic protocols for pediatric acute myeloid leukemia (AML) based on the BFM group experience were introduced in Poland. We retrospectively analyzed the results of pediatric AML treatment in Poland from 1983 to 2019 (excluding promyelocytic, therapy-related, biphenotypic, and Down syndrome AML). The study included 899 children suffering from AML treated with the following: AML-PPPLBC 83 (1983-1993, The probability of three-year overall survival was 0.34 ± 0.03, 0.37 ± 0.05, 0.54 ± 0.04, 0.67 ± 0.03, and 0.75 ± 0.05; event-free survival was 0.31 ± 0.03, 0.34 ± 0.05, 0.44 ± 0.04, 0.53 ± 0.03, and 0.67 ± 0.05; and relapse-free survival was 0.52 ± 0.03, 0.65 ± 0.05, 0.58 ± 0.04, 0.66 ± 0.03, and 0.78 ± 0.05, respectively, in the subsequent periods. A systematic reduction of early deaths and deaths in remission was achieved, while the percentage of relapses decreased only in the last therapeutic period. Surprisingly good results were obtained in the group of patients treated with AML-BFM 2012 with unfavorable genetic abnormalities like KMT2A-MLLT10/t(10;11)(p12;q23) and DEK-NUP214/t(6;9)(p23;q24), while unsatisfactory outcomes were found in the patients with FLT3-ITD. The use of standardized, systematically modified therapeutic protocols, with the successive consideration of genetic prognostic factors, and advances in supportive care led to a significant improvement in AML treatment outcomes over the last 40 years. Show less

Dietary fat absorption by the small intestine is a multistep process that regulates the uptake and delivery of essential nutrients and energy. One step of this process is the temporary storage of dietary fat in cytoplasmic lipid droplets (CLDs). The storage and mobilization of dietary fat is thought to be regulated by proteins that associate with the CLD; however, mechanistic details of this process are currently unknown. In this study we analyzed the proteome of CLDs isolated from enterocytes harvested from the small intestine of mice following a dietary fat challenge. In this analysis we identified 181 proteins associated with the CLD fraction, of which 37 are associated with known lipid related metabolic pathways. We confirmed the localization of several of these proteins on or around the CLD through confocal and electron microscopy, including perilipin 3, apolipoprotein A-IV, and acyl-CoA synthetase long-chain family member 5. The identification of the enterocyte CLD proteome provides new insight into potential regulators of CLD metabolism and the process of dietary fat absorption. Show less