Thurstonholst3728

Preeclampsia is characterized by the emergence of hypertension and proteinuria after 20 weeks of pregnancy, and it threatens both maternal and fetal lives if it proceeds unabated. Despite numerous studies, thus far the only fundamental therapy for preeclampsia is termination of pregnancy, leading to preterm birth. Furthermore, preeclamptic women are reported to be at risk for cardiovascular diseases for 10 years after delivery. Therefore, preventative and therapeutic strategies for preeclampsia are required. Recently, statins have been reported to improve the regeneration of vascular endothelium, and pravastatin has attracted attention as a potential preventative or therapeutic candidate for preeclampsia. Pravastatin has been demonstrated to have preventative effects in preeclampsia model mice, and a large volume of human data from pregnant women taking statins supports the safety of these drugs. Moreover, small clinical trials have reported that pravastatin has strong preventative or therapeutic effects on preeclampsia and it has the potential to improve the prognosis of pregnant women, fetuses and neonates affected by this condition.Background Galangin has been extensively studied as the antitumor agent in various cancers. However, the effect of galangin in hepatocellular carcinoma (HCC) remains elusive. Methods Using RNA sequencing, the differential expression of lncRNA in human HCC cell line with highly metastatic potential (MHCC97H) cells treated with galangin was investigated. Furthermore, H19 expression pattern was also determined in MHCC97H cells following treatment with galangin. In addition, knockdown and overexpression of H19 was performed to analyze the effect of the expression pattern of H19 on cell apoptosis, cell cycle, migration, and invasion in HCC cells. Moreover, the in vivo effect of galangin on tumor development was also determined in nude mice. learn more In order to analyze loss expression of H19 in vivo, clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) was used. Results Total of 50 lncRNAs were significantly differentially expressed in MHCC97H cells treated with galangin. Besides, the expression of H19 was markedly reduced following treatment with galangin in MHCC97H cells. Compared to the Control group, the galangin-treated group inhibited cell migration and invasion. Knockdown of H19 expression showed increased cell apoptosis and decreased invasion. In addition, RNA-seq data also identified 161 mRNA which was significantly differentially expressed following treatment with galangin. To further determine the underlying mechanism, p53 protein was analyzed. Notably, the results indicated that knockdown of H19 and miR675 induced the expression of p53, eventually promoting cell apoptosis in MHCC97H cells. These results indicated that galangin promoted cell apoptosis through reduced the expression of H19 and miR675 in MHCC97H cells. The in vivo result showed that compared to the Con, tumor growth was remarkably suppressed with loss expression of H19. Conclusion Our data suggested that galangin has a crucial role in hepatocarcinogenesis through regulating the expression pattern of H19.Bone marrow-derived cells contribute to tissue repair, but traffic of hematopoietic stem/progenitor cells (HSPCs) is impaired in diabetes. We therefore tested whether HSPC mobilization with the CXCR4 antagonist plerixafor improved healing of ischemic diabetic wounds. This was a pilot, phase IIa, double-blind, randomized, placebo-controlled trial (NCT02790957). Patients with diabetes with ischemic wounds were randomized to receive a single subcutaneous injection of plerixafor or saline on top of standard medical and surgical therapy. The primary endpoint was complete healing at 6 months. Secondary endpoints were wound size, transcutaneous oxygen tension (TcO2 ), ankle-brachial index (ABI), amputations, and HSPC mobilization. Twenty-six patients were enrolled 13 received plerixafor and 13 received placebo. Patients were 84.6% males, with a mean age of 69 years. HSPC mobilization was successful in all patients who received plerixafor. The trial was terminated after a preplanned interim analysis of 50% of the target population showed a significantly lower healing rate in the plerixafor vs the placebo group. In the final analysis data set, the rate of complete healing was 38.5% in the plerixafor group vs 69.2% in the placebo group (chi-square P = .115). Wound size tended to be larger in the plerixafor group for the entire duration of observation. No significant difference was noted for the change in TcO2 and ABI or in amputation rates. No other safety concern emerged. In conclusion, successful HSPC mobilization with plerixafor did not improve healing of ischemic diabetic wounds. Contrary to what was expected, outside the context of hematological disorders, mobilization of diabetic HSPCs might exert adverse effects on wound healing.Background Proximal esophageal striated muscle contractility may be abnormal in patients with esophageal symptoms, but is not assessed in the Chicago Classification (CC) v3.0. We aimed to (a) determine the prevalence of abnormal proximal esophageal contractility in patients with esophageal symptoms; (b) compare proximal esophageal contractility in patients with different esophageal motility disorders; (c) assess the association of abnormal proximal esophageal contractility with esophageal symptoms. Methods Patients undergoing high-resolution esophageal manometry (HREM) from 7/2019 to 11/2019 and healthy volunteers (HVs) were studied. Measurements of the proximal esophageal segment included the vigor of contractility of the proximal esophagus (proximal contractile integral/PCI). Patients rated gastrointestinal symptoms' severity. Key results HREM was performed on 221 patients (63.8% females, mean age 57.1 ± 1.1 years) and 19 HVs. Mean PCI in HVs was 299.5 ± 30.6 (95% CI 32.3-566.7 mm Hg. s. cm). Of all patients, 61 (27.6%) had abnormal PCI. HVs and patients with different esophageal motility disorders had significantly different PCI (P less then .01). Type 1 achalasia patients had weaker PCI than patients with absent contractility (P = .02). Patients with abnormal PCI had more severe dysphagia (P = .02), nausea (P = .03), vomiting (P = .03), and lower bolus clearance (P less then .01) than patients with normal PCI. Conclusions and inferences Abnormal PCI was found in a fourth of patients with esophageal symptoms. PCI may be useful to distinguish some esophageal motility disorders. Patients with abnormal PCI had a higher severity of some upper gastrointestinal symptoms than patients with normal PCI. Assessing the proximal esophageal segment on HREM may be useful in characterizing patients with esophageal symptoms.