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Therefore, this review aims to highlight major metabolic similarities between cancer cells and embryonic stem cells demonstrating that they have similar strategies in both signaling pathways regulation as well as metabolic profiles while focusing on key metabolites. Dihydroorotate dehydrogenase (DHODH) is an enzyme of the de novo pyrimidine synthesis pathway that provides nucleotides for RNA/DNA synthesis essential for proliferation. In mammalian cells, DHODH is localized in mitochondria, linked to the respiratory chain via the coenzyme Q pool. Here we discuss the role of DHODH in the oxidative phosphorylation system and in the initiation and progression of cancer. see more We summarize recent findings on DHODH biology, the progress made in the development of new, specific inhibitors of DHODH intended for cancer therapy, and the mechanistic insights into the consequences of DHODH inhibition. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists (SDH) with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. 9-point Likert scale questionnaires regarding 135 statements were administered. The RAND/UCLA appropriateness method was employed to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5-9 and disagreement index ≤1 were included in the guideline. For the final round, the guidelines were appraised by all the participants. An evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN are included. BACKGROUND Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, typically to a medication, that is characterized by fever, neutrophilia, and a disseminated non-follicular pustular eruption. AGEP is typically self-resolving upon withdrawal of the offending agent, however it is not without complications and distributive shock due to systemic inflammatory response can lead to hemodynamic instability and organ failure1-2. These patients have been successfully treated with systemic corticosteroids3. Cyclosporine use in patients with AGEP has been limited to only a few case reports4, 5. To date, no studies have evaluated the utility of cyclosporine in the management of AGEP. We report the largest cohort of patients with AGEP treated with cyclosporine and compare them to patients treated with systemic glucocorticoids. METHODS This was a retrospective study of adults admitted to Massachusetts General Hospital or Brigham and Women’s Hospital with a diagnosis of AGEP from 2009-2019.rences in the setting of the aforementioned comorbidities, some selection bias was unavoidable in this cohort. The small sample size and retrospective nature also limit this study. Nevertheless, cyclosporine appears to be a non-inferior therapeutic alternative to glucocorticoids in the appropriate patient who presents with AGEP, and future prospective studies are needed to further examine its utility in AGEP. Celastrol is a natural pentacyclic triterpene extracted from the roots of Tripterygium wilfordi (thunder god vine). Celastrol was reported as a powerful anti-obesity drug with leptin sensitizing properties that decreases food consumption and mediates body weight loss when administered to diet-induced obese mice at 100 μg/kg body weight. The weight lowering properties of celastrol are likely mediated by the CNS, in particular, by the hypothalamus, but the final proof for the accumulation of celastrol in the brain and hypothalamus remains to be established. Here, we aimed to demonstrate that intraperitoneal celastrol administration at 100 μg/kg can rapidly reach the brain and, in particular, the hypothalamus of mice. We developed and validated a sensitive liquid chromatography mass spectrometry method for the quantitative determination of celastrol in murine tissues, namely liver, brain and hypothalamus. Chow-fed lean mice were randomly assigned to the vehicle vs. celastrol groups, injected with saline or 100 μg/kg body weight of celastrol, and sacrificed 30 min or 120 min post injection. Celastrol was extracted from homogenized tissue using ethyl acetate as organic solvent, and quantified using a matrix-matched calibration curve with glycyrrhetinic acid as internal standard. Liver celastrol concentrations were 32.60 ± 8.21 pg/mg and 40.52 ± 15.6 pg/mg, 30 and 120 min after injection, respectively. We found 4.70 ± 0.31 pg/mg celastrol after 30 min, and 16.22 ± 3.33 pg/mg after 120 min in whole brain lysates, and detectable amounts in the hypothalamus. These results corroborate the validity of our methodology, demonstrate the accumulation of celastrol in the brain of mice injected intraperitoneally with a dose of 100 μg/kg, and confirm the CNS as possible site of action for the weight lowering properties of celastrol. Endothelins including its most abundant isoform, endothelin-1 (ET-1), are peptides acting as vasoconstrictors when binding to ETA and ETB receptors, and, in addition to their distinct roles in normal physiology, endothelins have a central role in the pathophysiology of many diseases including cardiovascular and renal diseases. Endothelin-1 (ET-1), the most potent vasoconstrictor in the cardiovascular system, regulates basal vascular tone and glomerular hemodynamics. ET-1 is involved also in vascular and cardiac hypertrophy, inflammation, and in the development and progression of cardiovascular diseases – e.g. essential hypertension, atherosclerosis, coronary artery disease, congestive heart failure, pulmonary arterial hypertension and cerebrovascular disease and renal diseases – e.g. acute renal failure, polycystic kidney disease and chronic kidney disease. Not surprisingly, the ET system has become a target for therapeutic interventions that now include a few already established and some new promising agents.