Search results for "pancreas"
showing 10 items of 231 documents
Overexpression of glucose 6 phosphate dehydrogenase preserves mouse pancreatic beta cells function until late in life.
2021
NAD(P)H donates electrons for reductive biosynthesis and antioxidant defense across all forms of life. Glucose-6- phosphate dehydrogenase (G6PD) is a critical enzyme to provide NADPH. G6PD deficiency is present in more than 400 million people worldwide. This enzymopathy provides protection against malaria but sensitizes cells to oxidative stressors. Oxidative stress has been involved in the pathogenesis of the diabetic complications and several studies have provided evidences of a link between G6PD deficiency and type 2 diabetes (T2D). We hypothesized that a moderate overexpression of G6PD (G6PD-Tg) could protect β-cells from age-associated oxidative stress thus reducing the risk of develop…
Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review
2021
Simple Summary Pancreatic cancer is a digestive tumor that is most difficult to treat and carries one of the worst prognoses. The anatomical location of the pancreas makes it very difficult to obtain enough tumor material to establish a molecular diagnosis, so knowing the biology of this tumor and implementing new targeted-therapies is still a pending issue. The use of liquid biopsy, a blood sample test to detect circulating-tumor DNA fragments (ctDNA), is key to overcoming this difficulty and improving the evolution of this tumor. Liquid biopsies are equally representative of the tissue from which they come and allow relevant molecular and diagnostic information to be obtained in a faster …
Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis
2016
Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates…
Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis
2016
Background Obesity has tremendous impact on the health systems. Its epigenetic bases are unclear. MacroH2A1 is a variant of histone H2A, present in two alternatively exon-spliced isoforms macroH2A1.1 and macroH2A1.2, regulating cell plasticity and proliferation, during pluripotency and tumorigenesis. Their role in adipose tissue plasticity is unknown. Results Here, we show evidence that macroH2A1.1 protein levels in the visceral adipose tissue of obese humans positively correlate with BMI, while macroH2A1.2 is nearly absent. We thus introduced a constitutive GFP-tagged transgene for macroH2A1.2 in mice, and we characterized their metabolic health upon being fed a standard chow diet or a hig…
Telomerase and pluripotency factors jointly regulate stemness in pancreatic cancer stem cells
2021
© 2021 by the authors.
Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real-world study.
2018
Abstract Introduction Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty. Aim To evaluate sunitinib efficacy and tolerability in panNETs patients treated in a real-world setting. Patients and methods Retrospective analysis of progressive panNETs treated with sunitinib. Efficacy was assessed by evaluating progression-free survival, overall survival, and disease control (DC) rate (stable disease (SD) + partial response + complete response). Data are reported as median (25th–75th IQR). Results Eighty patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had NET G3 neoplasms. A total of 53 patients (66.3…
Elevated Serum Fibroblast Growth Factor 21 in Humans with Acute Pancreatitis.
2016
Background The metabolic regulator Fibroblast Growth Factor 21 (FGF21) is highly expressed in the acinar pancreas, but its role in pancreatic function is obscure. It appears to play a protective role in acute experimental pancreatitis in mice. The aim of this study was to define an association between FGF21 and the course and resolution of acute pancreatitis in humans. Methods and Principal Findings Twenty five subjects with acute pancreatitis admitted from May to September 2012 to the Beth Israel Deaconess Medical Center (BIDMC) were analyzed. Serial serum samples were collected throughout hospitalization and analyzed for FGF21 levels by ELISA. Twenty healthy subjects sampled three times o…
Unexpected subcellular distribution of a specific isoform of the Coxsackie and adenovirus receptor, CAR-SIV, in human pancreatic beta cells
2018
Aims/hypothesis: The Coxsackie and adenovirus receptor (CAR) is a transmembrane cell-adhesion protein that serves as an entry receptor for enteroviruses and may be essential for their ability to infect cells. Since enteroviral infection of beta cells has been implicated as a factor that could contribute to the development of type 1 diabetes, it is often assumed that CAR is displayed on the surface of human beta cells. However, CAR exists as multiple isoforms and it is not known whether all isoforms subserve similar physiological functions. In the present study, we have determined the profile of CAR isoforms present in human beta cells and monitored the subcellular localisation of the princi…
Two different pathogenic mechanisms, dying-back axonal neuropathy and pancreatic senescence, are present in the YG8R mouse model of Friedreich ataxia
2016
Frataxin (FXN) deficiency causes Friedreich's ataxia (FRDA), a multisystem disorder with neurological and non-neurological symptoms. FRDA pathophysiology combines developmental and degenerative processes of dorsal root ganglia (DRG), sensory nerves, dorsal columns and other central nervous structures. A dying-back mechanism has been proposed to explain the peripheral neuropathy and neuropathology. In addition, affected individuals have non-neuronal symptoms such as diabetes mellitus or glucose intolerance. To go further in the understanding of the pathogenic mechanisms of neuropathy and diabetes associated with the disease, we have investigated the humanized mouse YG8R model of FRDA. By bio…
Molecular aspects of pancreatic β-cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA.
2018
Metabolic syndrome is known as a frequent precursor of type 2 diabetes mellitus (T2D). This disease could affect 8% of the people worldwide. Given that pancreatic β-cell dysfunction and loss have central roles in the initiation and progression of the disease, the understanding of cellular and molecular pathways associated with pancreatic β-cell dysfunction can provide more information about the underlying pathways involved in T2D. Multiple lines evidence indicated that oxidative stress, microRNA, and long noncoding RNA play significant roles in various steps of diseases. Oxidative stress is one of the important factors involved in T2D pathogenesis. This could affect the function and surviva…