Buschkold8360
Moreover, BA could downregulate the expression of VASP at the protein and mRNA level by inhibiting NF-κB activity. In conclusion, these results suggest that BA could inhibit the expression of VASP by negatively regulating NF-κB, thereby inhibiting the proliferation and migration of the GC cells. Our study provides a theoretical basis for exploring the molecular mechanism underlying BA-induced inhibition of proliferation and migration in GC cells.
we know little about clinical outcomes of arterial calcifications. This study investigates the risk factors of intracranial artery calcifications and its association with cardiovascular disease and cognitive function.
patients were recruited from a Dutch memory clinic, between April 2009 and April 2015. The intracranial internal carotid artery (iICA) and basilar artery were analysed on the presence of calcifications. Calcifications in the iICA were also assessed on severity and location in the tunica intima or tunica media. Using logistic regression, risk factors of intracranial artery calcifications were analysed, as well as the association of these calcifications with cardiovascular disease, cognitive function and type of cognitive disorder (including subjective cognitive impairment, mild cognitive impairment and dementia). Cognitive function was assessed with the Cambridge Cognitive Examination.
1992 patients were included (median age 78.2 years, ±40% male). The majority of patients had calcificationiated with myocardial infarction and stroke, but not with cognitive outcomes.Experimental observations in lipid monolayers at the air-water interface have demonstrated that solitary sound pulses can be excited. These pulses propagate electrical, chemical, and thermal variations in addition to the mechanical changes in lateral pressure and lipid density, and can interact with nearby ions, polymers, and water. In addition, it was demonstrated that sound pulses that reversibly traverse the melting transition between the so-called liquid-expanded and liquid-condensed phases display unusual nonlinear properties that are strikingly similar to those of action potentials in living cells. This review describes recent experimental and theoretical investigations of sound in lipid membranes and their potential function in biology.Severe acute pancreatitis (SAP) is a non-bacterial inflammatory disease that clinically causes a very high rate of mortality. Dihydrokaempferol (DHK) is a natural flavonoid extracted from Bauhinia championii. Our research aimed to establish the treatment function of DHK on SAP-induced pancreas injury and delve into its potential mechanism. In this study, SAP was induced by caerulein (CER) and Lipopolysaccharide (LPS). DHK was administered orally at different doses of 20, 40, or 80 mg/kg. Results from serum amylase/lipase, pancreas hematoxylin-eosin staining technique, pancreas malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) showed the therapeutic effect of DHK in a mice SAP model. MTT revealed DHK alleviated CER + LPS induced cytotoxicity in a dose-dependent manner in the pancreatic acinar cells of mice. Next, we verified DHK suppressed the level of Keap1 and promoted transcriptional activation of nuclear Nrf2 in the presence of CER + LPS. The molecular docking study suggested that there is a potential interaction between DHK and Keap1. selleck products To further look at the role of Keap1 using in vitro and in vivo models, Keap1 overexpression adenovirus (ad-Keap1) was performed. The results revealed that ad-Keap1suppressed the nuclear translocation of Nrf2 which is enhanced by DHK, and suppressed the antioxidative functionality of DHK both in mice and cell models. Collectively, this research demonstrated that DHK bettered the SAP induced pancreas injury by regulating the Keap1/Nrf2 pathway and regulating oxidative stress injury.
Lipopolysaccharide (LPS) induces inflammatory cholestasis by impairing expression, localization, and function of carriers involved in bile formation, e.g. bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2). A specific therapy against this disease is still lacking. Therefore, we evaluated the anticholestatic effects of spironolactone (SL), a PXR ligand that regulates bile salt homeostasis, up-regulates Mrp2, and bears anti-inflammatory properties.
Male Wistar rats were divided into four groups Control, SL (83.3mg/kg/day of SL, i.p., for 3days), LPS (2.5mg/kg/day, i.p., at 8am of the last 2days, and 1.5mg/kg/day at 8pm of the last day), and SL+LPS. Biliary and plasma parameters and the expression, function, and localization of Mrp2 and Bsep were evaluated.
SL partially prevented LPS-induced drop of basal bile flow by normalizing the bile salt-independent fraction of bile flow (BSIBF), via improvement of glutathione output. This was due to a recovery in Mrp2 transport function, the major canalicular glutathione transporter, estimated by monitoring the output of its exogenously administered substrate dibromosulfophthalein. SL counteracted the LPS-induced downregulation of Mrp2, but not that of Bsep, at both mRNA and protein levels. LPS induced endocytic internalization of both transporters, visualized by immunofluorescence followed by confocal microscopy, and SL partially prevented this relocalization. SL did not prevent the increase in IL-1β, IL-6, and TNF-α plasma levels.
SL prevents the impairment in Mrp2 expression and localization, and the resulting recovery of Mrp2 function normalizes the BSIBF by improving glutathione excretion.
SL prevents the impairment in Mrp2 expression and localization, and the resulting recovery of Mrp2 function normalizes the BSIBF by improving glutathione excretion.
3,3'-Diindolylmethane (DIM) has limited anti-cancer effects in gastric cancer. Hydrogen sulfide (H
S) plays an important role in the tumor development and therapy, cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE), two key endogenous H
S biosynthesis enzymes, can affect endogenous H
S levels and alter cancer treatment. Our main objective was to investigate whether the aminooxyacetic acid (AOAA) and DL-Propargylglycine (PAG), two specific inhibitors of CBS and CSE, could assist DIM to exert a stronger anti-cancer effects in gastric cancer BGC-823 and SGC-7901 cells.
Cell proliferation was assayed by MTT and cell colony-forming assay. Apoptosis and migration were detected by Hoechst staining and scratch test respectively. Western blot was used to evaluate the expression of proteins related to proliferation, apoptosis and migration.
Combination of AOAA or PAG with DIM synergistically inhibited proliferation and migration, increased apoptosis in gastric cancer cells. The p38-p53 axis was also further activated by the combination of AOAA or PAG with DIM.
