Carlsonbak0998

Vitamin D deficiency is a worldwide pandemic and results in osteoporosis, hypertension, and other cardiovascular diseases. At the cellular level, it produces significant oxidative stress, inflammatory markers, and mitochondrial damage. There is increasing evidence about the role of vitamin D in the regulation of the renin-angiotensin-aldosterone system (RAAS). Moreover, there is evidence of involvement in cardiovascular complications, as well as in the immune system disorders. Vitamin D values below 25ng/mL are related to an increase in vascular tone mediated by smooth muscle contraction. Furthermore, it can produce direct effects on vascular smooth muscle cells, RAAS over-regulation, modulation of calcium metabolism, and secondary hyperparathyroidism. All this predisposes patients to develop hypertrophy of the left ventricle and vascular wall, causing hypertension. In this work, a review is presented of the main mechanisms involved in the development of hypertension due to vitamin D deficiency. Among them are the link established between the levels of extra-mitochondrial inorganic phosphate, its main regulatory hormones -such as vitamin D-, the cardiovascular system, reactive oxygen species, and mitochondrial metabolism. The role of the mitochondrial vitamin D receptor and the regulation of the respiratory chain could influence arterial remodelling since its activation would reduce oxidative damage and preserve cell life. However, there are aspects not yet understood about the intricate signalling network that appeared simple in experimental trials, but complex in clinical studies. In this way, the completion of new studies as VITAL, could clarify, and thus support or refute the possible benefits of vitamin D in hypertensive cardiovascular disease.Background and objective Liver transplantation (LT) is the gold-standard treatment for end-stage liver disease; however, late-onset complications such as fatty liver can occur in the absence of metabolic comorbidities. We report a unique case of post-transplant hepatic steatosis developing in only a part of the liver graft. Case report A 1-year-old boy underwent ABO-incompatible living donor liver transplantation (LDLT) with a left lateral liver graft donated from his mother for biliary atresia. The biliary tract was reconstructed by hepaticojejunostomy using the previous Roux-en-Y limb. Liver function tests increased by up to 2-fold of the upper normal limit after the second year. He developed segmental steatosis in a part of the liver graft 2 years after LDLT. Venous blood drained into the area of the liver graft from veins in the Roux-en-Y limb of the jejunum. Pathologic findings from a liver biopsy showed fatty depositions without steatohepatitis, acute rejection, or tumors. Portal vein stricture (PVS) subsequently became apparent, which was complicated by the symptoms of portal hypertension, such as gastrointestinal varices. We treated PVS with 2 sessions of percutaneous transhepatic portal vein angioplasty (PTPA), after which the segmental steatosis disappeared. We hypothesize that PVS caused local hemodynamic anomalies, leading to fatty deposition in a part of the liver graft. Conclusion We experienced a case of post-LT with segmental steatosis that was successfully treated by portal vein flow modification with PTPA. Steatosis of the graft might indicate a vascular abnormality, and further examinations should be performed after LT.GATA1 is a master transcription factor of megakaryopoiesis and erythropoiesis, and loss-of-function mutation can induce accumulation of megakaryocyte-erythroid progenitors (MEPs) in mice and humans. Accordingly, the murine MEP cell line (termed G1ME2 cells) encoding doxycycline (dox)-inducible anti-Gata1 shRNA on Hprt locus has been developed. The cells were CD41+CD71+KIT+, expand under dox, stem cell factor, and thrombopoietin (TPO), and terminally differentiate into erythroid cells or megakaryocytes upon removal of dox. Surprisingly, in this study, these Gata1low murine MEPs displayed accelerated growth from around 90-100 days after cell culture, impeded megakaryocytic potential, and maintained erythropoiesis. We specified them as late G1ME2 cells and discovered that increased CD41-KIT+ population during long-term culture was the main reason for the delayed megakaryopoiesis. The CD41 expression level was partially de-repressed by PI3K/AKT inhibitors, suggesting that TPO-mediated cell survival signaling pathway might have impacted on CD41 in the late G1ME2 cells. Nevertheless, among the late cells, the CD41+KIT+ cells could still generate megakaryocytes on dox withdrawal. Taken together, G1ME2 cells could provide a good model to study molecular mechanism of hematopoiesis because of their ability to expand excessively without artificial immortalization.The acquisition of chemoresistance is a major clinical challenge for pancreatic cancer (PC) treatment. Chemoresistance is largely attributed to aberrant DNA damage repair. However, the underlying mechanisms of chemoresistance in pancreatic cancer remain unclear. Here, we showed that CD147 was strongly correlated to DNA damage response (DDR) indices and poor prognosis in pancreatic ductal adenocarcinoma (PDAC) patients. CD147 knockdown or monoclonal antibodies improved the killing effects of gemcitabine in gemcitabine resistant cells, exhibiting reduced activation of ATM/p53. Moreover, we found the interaction of CD147 with ATM, ATR and p53, which was augmented in gemcitabine resistant cells. High CD147/p-ATM/p-ATR/p-p53 cytoplasmic expression associated with poor survival of PC patients. Our studies thus identify CD147 as a critical player in DDR programing that affects gemcitabine therapeutic outcomes of pancreatic cancer patients.Negatively charged synthetic hydrogels have been known to facilitate various cellular responses including cell adhesion, proliferation, and differentiation; however, the molecular mechanism of hydrogel-dependent control of cell behavior remains unclear. Recently, we reported that negatively charged poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel induces chondrogenic differentiation of ATDC5 cells via novel protein reservoir function. In this study, we identified the cell adhesion molecules binding to PAMPS gels that act as mechanoreceptors. First, we performed a pull-down assay by particle gels using cell membrane proteins of ATDC5, and found that multiple membrane proteins bound to the PAMPS gel, whereas the uncharged poly(N,N'-dimethylacrylamide) gel as control did not bind to any membrane proteins. Western blot analysis indicated differential binding of integrin (ITG) isoforms to the PAMPS gel, in which the α4 isoform, but not α5 and αv, efficiently bound to the PAMPS gel. selleck chemicals ITG α4 knockdown decreased cell spreading of ATDC5 on PAMPS gels, whereas the enhanced expression increased the behavior.