Reduction in Serum Carotenoid Levels Following One Anastomosis Gastric Bypass.

Given the health benefits of carotenoids, it is crucial to evaluate their levels in patients undergoing malabsorptive procedures like one anastomosis gastric bypass (OAGB). This study aimed to assess serum carotenoid levels before and 6 months following OAGB. Prospectively collected data from patients who underwent primary OAGB were analyzed.

Gene deletion of Interleukin-1α reduces ER stress-induced CHOP expression in macrophages and attenuates the progression of atherosclerosis in apoE-deficient mice.

The pathophysiology of atherosclerosis initiation and progression involves many inflammatory cytokines, one of them is interleukin (IL)-1α that has been shown to be secreted by activated macrophages. We have previously shown that IL-1α from bone marrow-derived cells is critical for early atherosclerosis development in mice. It is known that endoplasmic reticulum (ER) stress in macrophages is involved in progression to more advanced atherosclerosis, but it is still unknown whether this effect is mediated through cytokine activation or secretion.

Second pregnancy following kidney transplantation is not associated with an increased risk of graft loss in a single center retrospective cohort study.

Introduction: Previous studies on first pregnancy following kidney transplantation (KT) show no association with decreased graft survival. This study examined patients with multiple gestations compared to a single pregnancy following KT and evaluated the risk of graft function deterioration.

Methods: A retrospective cohort study on fertile female kidney transplant recipients (KTRs) from Rabin Medical Center between January 2001 and December 2017 was performed.

Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors.

Argininosuccinate synthase (ASS1) downregulation in different tumors has been shown to support cell proliferation and yet, in several common cancer subsets ASS1 expression associates with poor patient prognosis. Here we demonstrate that ASS1 expression under glucose deprivation is induced by c-MYC, providing survival benefit by increasing nitric oxide synthesis and activating the gluconeogenic enzymes pyruvate carboxylase and phosphoenolpyruvate carboxykinase by S-nitrosylation. The resulting increased flux through gluconeogenesis enhances serine, glycine and subsequently purine synthesis.

Acid-Induced Downregulation of ASS1 Contributes to the Maintenance of Intracellular pH in Cancer.

Downregulation of the urea cycle enzyme argininosuccinate synthase (ASS1) by either promoter methylation or by HIF1α is associated with increased metastasis and poor prognosis in multiple cancers. We have previously shown that in normoxic conditions, ASS1 downregulation facilitates cancer cell proliferation by increasing aspartate availability for pyrimidine synthesis by the enzyme complex CAD. Here we report that in hypoxia, ASS1 expression in cancerous cells is downregulated further by HIF1α-mediated induction of miR-224-5p, making the cells more invasive and dependent on upstream substrates of ASS1 for survival.

Rewiring urea cycle metabolism in cancer to support anabolism.

Cancer cells reprogramme metabolism to maximize the use of nitrogen and carbon for the anabolic synthesis of macromolecules that are required during tumour proliferation and growth. To achieve this aim, one strategy is to reduce catabolism and nitrogen disposal. The urea cycle (UC) in the liver is the main metabolic pathway to convert excess nitrogen into disposable urea.

Urea Cycle Dysregulation Generates Clinically Relevant Genomic and Biochemical Signatures.

The urea cycle (UC) is the main pathway by which mammals dispose of waste nitrogen. We find that specific alterations in the expression of most UC enzymes occur in many tumors, leading to a general metabolic hallmark termed "UC dysregulation" (UCD). UCD elicits nitrogen diversion toward carbamoyl-phosphate synthetase2, aspartate transcarbamylase, and dihydrooratase (CAD) activation and enhances pyrimidine synthesis, resulting in detectable changes in nitrogen metabolites in both patient tumors and their bio-fluids.

Arginine and the metabolic regulation of nitric oxide synthesis in cancer.

Nitric oxide (NO) is a signaling molecule that plays important roles in diverse biological processes and thus its dysregulation is involved in the pathogenesis of various disorders. In cancer, NO has broad and sometimes dichotomous roles; it is involved in cancer initiation and progression, but also restricts cancer proliferation and invasion, and contributes to the anti-tumor immune response. The importance of NO in a range of cellular processes is exemplified by its tight spatial and dosage control at multiple levels, including via its transcriptional, post-translational and metabolic regulation.

c-Abl forces YAP to switch sides.

Cancer research has been significantly accelerated by viewing cancer as a functional collision between 2 dichotomous sets of genes: oncogenes and tumor suppressors. Signaling pathways turn oncogenes and tumor suppressors on and off to dictate cell fate decisions. We contend that signaling also dictates opposing behaviors of a given effector.

Dual Regulatory Role of Polyamines in Adipogenesis.

Adipogenesis is a complex process, accompanied by a chain of interdependent events. Disruption of key events in this cascade may interfere with the correct formation of adipose tissue. Polyamines were demonstrated necessary for adipogenesis; however, the underlying mechanism by which they act has not been established.

c-Abl tyrosine kinase promotes adipocyte differentiation by targeting PPAR-gamma 2.

Adipocyte differentiation, or adipogenesis, is a complex and highly regulated process. A recent proteomic analysis has predicted that the nonreceptor tyrosine kinase Abelson murine leukemia viral oncogene (c-Abl) is a putative key regulator of adipogenesis, but the underlying mechanism remained obscure. We found that c-Abl was activated during the early phase of mouse 3T3-L1 preadipocyte differentiation.

Targeting ErbB-1 and ErbB-4 in irradiated head and neck cancer: results of in vitro and in vivo studies.

Background: ErbB oncogenes have a major role in cancer. The role of ErbB-4 in cancer cell biology and the effect of anti-ErbB-1 and anti-ErbB-4 monoclonal antibodies were evaluated in this study.

Methods: ErbB-4 expression and binding was evaluated by Western blot, enzyme-linked immunosorbent assay (ELISA), fluorescent microscopy, and flow cytometry.

Diagnostic and prognostic significance of serum C-reactive protein levels in patients admitted to the department of medicine.

Background: : Despite its apparent role as a marker of different disease processes, to date, no study has presented comprehensive comparative data regarding the distribution of serum C-reactive protein (CRP) levels in all admitted patients. We aimed to examine the distribution of serum CRP levels in internal medicine patients and to find whether initial serum CRP value had a diagnostic and prognostic significance.

Methods: : Serum CRP levels together with epidemiologic, clinical, and laboratory data were analyzed for 370 consecutive adult patients admitted to the department of internal medicine during a 2-month period.