scholarly journals Effects of Sphingolipid Fractions from Golden Oyster Mushroom (Pleurotus citrinopileatus) on Apoptosis Induced by Inflammatory Stress in an Intestinal Tract in vitro Model

2020 ◽  
Vol 69 (9) ◽  
pp. 1087-1093
Author(s):  
Mirinthorn Jutanom ◽  
Chisato Higaki ◽  
Shinji Yamashita ◽  
Kiyotaka Nakagawa ◽  
Satoshi Matsumoto ◽  
...  
ACS Omega ◽  
2021 ◽  
Vol 6 (4) ◽  
pp. 3140-3148
Author(s):  
Ephantus Nguma ◽  
Shinji Yamashita ◽  
Kei Kumagai ◽  
Yurika Otoki ◽  
Ayaka Yamamoto ◽  
...  

2009 ◽  
Vol 53 (4) ◽  
pp. 1377-1385 ◽  
Author(s):  
Tse-I Lin ◽  
Oliver Lenz ◽  
Gregory Fanning ◽  
Thierry Verbinnen ◽  
Frédéric Delouvroy ◽  
...  

ABSTRACT The hepatitis C virus (HCV) NS3/4A serine protease has been explored as a target for the inhibition of viral replication in preclinical models and in HCV-infected patients. TMC435350 is a highly specific and potent inhibitor of NS3/4A protease selected from a series of novel macrocyclic inhibitors. In biochemical assays using NS3/4A proteases of genotypes 1a and 1b, inhibition constants of 0.5 and 0.4 nM, respectively, were determined. TMC435350 inhibited HCV replication in a cellular assay (subgenomic 1b replicon) with a half-maximal effective concentration (EC50) of 8 nM and a selectivity index of 5,875. The compound was synergistic with alpha interferon and an NS5B inhibitor in the replicon model and additive with ribavirin. In rats, TMC435350 was extensively distributed to the liver and intestinal tract (tissue/plasma area under the concentration-time curve ratios of >35), and the absolute bioavailability was 44% after a single oral administration. Compound concentrations detected in both plasma and liver at 8 h postdosing were above the EC99 value measured in the replicon. In conclusion, given the selective and potent in vitro anti-HCV activity, the potential for combination with other anti-HCV agents, and the favorable pharmacokinetic profile, TMC435350 has been selected for clinical development.


2017 ◽  
Vol 6 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Yuchi Jia ◽  
Xiaomei Wu

Abstract Objective We aimed to evaluate the combined antibacterial effects of allicin in combination with levofloxacin and ceftriaxone on Shigella isolated from the intestinal tract in vitro. Materials and Methods Using a checkerboard design, broth microdilution assay was used to test the effects of the compounds on the organism. We also determined the MIC of the two groups of antibacterial drugs against 30 strains of Shigella and calculated the fractional inhibitory concentration (FIC) index, to judge the combination effect. Result After the combined application of allicin and ceftriaxone the MIC decreased significantly. Distribution of the FIC index was as follows: FIC ≤0.5, accounting for 10%; 0.5< FIC ≤1.0, accounting for 60%; 1 < FIC ≤2, accounting for 30%; FIC >2, percentage is zero. After combined application of allicin and levofloxacin, distribution of FIC index was as follows: FIC≤0.5, ratio is zero; 0.5< FIC ≤1, accounting for 56.7%; 1 < FIC ≤2, accounting for 43.3%; FIC >2, ratio is zero. Conclusion After the combined use of ceftriaxone, levofloxacin, and allicin, most of the tests showed synergistic effects and additive effects on Shigella, while some of them showed no correlation and no antagonistic effect.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Islam Mohamed ◽  
Sheena Thomas ◽  
Kimberly Rooney ◽  
Roy Sutliff ◽  
Nick Willett ◽  
...  

Introduction: Shear stress forces play an integral role in dictating the endothelial cell (EC) response to changes in blood flow, pro-inflammatory response and hence development of atherosclerosis. Previously, our group has identified EC microRNA-155 (miR-155) as one of the key signature dysregulated miRNAs in areas of chronic low magnitude oscillatory shear stress (OSS) in vasculature and OSS models of in-vitro. Hypothesis: we hypothesized that acute induction of OSS mediates EC oxidative stress, inflammation and dysfunction, via dysregulation of EC miR-155. Methods: 12-week old C57B/6J mice were subjected to abdominal aortic coarctation (AAC), a unique model of acute induction of OSS, for 3 days and downstream segments of acute OSS were compared to upstream unidirectional shear stress (USS) segments of the thoracic aorta. Results: Acute OSS resulted in down regulation of EC miR-155 expression and inverse upregulation of EC RhoA and Myosin light chain kinase (MYLK), known targets of miR-155-mediated EC cytoskeleton organization, in OSS segments compared with USS. This was associated with impaired EC dependent relaxation, differential contractile response to phenylephrine, and loss of EC barrier function as evaluated by extravasation of Evans-blue dye assay. In parallel, En-face immunohistochemical staining also showed increased expression of EC nitric oxide synthase (eNOS) along with increased levels of reactive oxygen species (ROS) and nitrotyrosine (NY) formation in OSS segments compared with USS. Conclusions: Together, our studies shed light on the early changes in EC response to acute induction of OSS and resulting down-regulation of EC mir-155, including; oxidative/inflammatory stress, EC dysfunction, loss of barrier function and cytoskeletal changes. Despite the early upregulation of eNOS, it could also potentially synergize with the activation of the RhoA-MYLK pathway in EC oxidative (ROS/NY)/inflammatory stress and associated EC dysfunction. Further studies are in progress to dissect the interplay between these different pathways and their causal relationships as downstream targets of EC miR-155.


2001 ◽  
Vol 47 (1) ◽  
pp. 91-95 ◽  
Author(s):  
J Wayne Conlan ◽  
Sonia L Bardy ◽  
Rhonda KuoLee ◽  
Ann Webb ◽  
Malcolm B Perry

In an attempt to improve upon a current mouse model of intestinal colonization by Escherichia coli O157:H7 used in this laboratory for vaccine development, nine clinical isolates of the pathogen were screened for their ability to persist in the intestinal tract of conventional adult CD-1 mice. None of the test isolates of E. coli O157:H7 were capable of colonizing these mice for a period of more than two weeks. Most of the isolates appeared to be benign for the experimental host, but one isolate was lethal. This virulence correlated with the ability of the latter isolate to produce large quantities of Shiga-like toxin 2 in vitro.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Fan Yang ◽  
Haoran Hu ◽  
Wenjing Yin ◽  
Guangyi Li ◽  
Ting Yuan ◽  
...  

Background. Platelet-rich plasma (PRP) has been shown to be a promising therapeutic agent against osteoarthritis (OA), whereas its chondroprotection mechanism is not fully elucidated. Autophagy is considered an important biological process throughout the development of OA. Therefore, the objective of the present study is to investigate the role of autophagy in the chondroprotection and compare the effects of releasate between L-PRP and P-PRP. Methods. PRP were prepared from rat blood. Rat chondrocytes pretreated in the presence or absence of interleukin-1 beta (IL-1β) were incubated with PRP releasate. The expressions of OA-related genes and autophagy-related genes were determined by RT-PCR and western blot, respectively. Autophagic bodies were assessed by transmission electron microscopy and the autophagy flux was monitored under the confocal microscopy. The effect of PRP on autophagy was further investigated in the milieu of autophagy activator, rapamycin, or autophagy inhibition by downregulation of Atg5. The effect of PRP on cartilage repair and autophagy was also evaluated in an OA rat model. Results. In vitro, PRP releasate increased the expression of the anabolic genes, COL2 and Aggrecan, and decreased the expression of the catabolic genes, whereas the expression of autophage markers, Atg5 and Beclin-1, as well as the ratio of LC3 II/LC3 I, was not significantly altered in normal or IL-1β-treated chondrocytes. Similar expression pattern was found following the activation (rapamycin) or inhibition (Atg5 silencing) of autophagy. In vivo, PRP releasate ameliorated posttraumatic cartilage degeneration while the expression of LC3 was comparable to that in the vehicle treatment group. Conclusions. PRP releasate promoted the anabolic gene expression, relieved inflammatory stress in chondrocytes, and ameliorated cartilage degeneration, but autophagy was independent of these processes.


1987 ◽  
Vol 10 (4) ◽  
pp. 269-274 ◽  
Author(s):  
E.A. Wolfe ◽  
T.M.S. Chang

Dialysis is the conventional treatment for chronic renal failure. It is cumbersome, expensive and time-consuming and thus alternate treatments have long been sought. A compact system consisting of haemoperfusion in series with ultrafiltration can nearly replace dialysis. A urea removal system is the only step required to complete this approach. The potential of combining a microencapsulated enzyme, urease, with an ammonium ion adsorbent, zirconium phosphate, to remove urea was examined in vitro. Urease converts urea to ammonium ions which are then adsorbed on-to zirconium phosphate. This combination would be most effective in the intestinal tract. The capacity of zirconium phosphate is probably not enough to effect the removal of enough urea to completely replace dialysis in patients with no renal function. However, this system could potentially 1) delay the onset of dialysis therapy in patients who still have some renal function, either alone or in combination with haemoperfusion-ultrafiltration, or 2) reduce dialysis treatment times.


Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1422
Author(s):  
Alexandro Barbosa de Souza ◽  
Marco Vinícius Chaud ◽  
Thais Francine Alves ◽  
Juliana Ferreira de Souza ◽  
Maria Helena Andrade Santana

Oral hyaluronic acid (HA) is a ubiquitous biopolymer that has gained attention as a treatment for local or systemic diseases. Here, we prepared and characterized structures of free HA (f-HA) with a high (>105 Da), intermediate (≤105 Da), and low (≤104 Da) average molar mass (MM); nanoparticles crosslinked with adipic dihydrazide (n-HA); and mixed formulations (mixed-HA) containing f-HA and n-HA. MM distribution determined the structure, hydrodynamic diameter, and zeta potential of the f-HAs. Crosslinking changed the physicochemical properties in n-HA. In vitro tack adhesion assays, using mucin tablets or a viable rat intestinal mucosa, showed better mucoadhesion with f-HA (intermediate MM) and mixed-HA (25% n-HA), especially in the jejunum segment. High MM f-HA presented negligible mucoadhesion. n-HA showed the deepest diffusion into the porous of the membranes. In vivo results showed that, except for high MM f-HA, there is an inverse relationship between rheological changes in the intestinal membrane macerates resulting from mucoadhesion and the effective intestinal permeability that led to blood clearance of the structures. We conclude that the n-HA formulations are promising for targeting other tissues, while formulations of f-HA (intermediate MM) and mixed-HA are better for treating dysbiosis.


2014 ◽  
Vol 112 (10) ◽  
pp. 781-788 ◽  
Author(s):  
Vanessa Roldán ◽  
Ana Belen Arroyo ◽  
Sallam Salloum-Asfar ◽  
Sergio Manzano-Fernández ◽  
Nuria García-Barberá ◽  
...  

SummaryThere are few biomarkers able to forecast new thrombotic events in patients with AF. In this framework, microRNAs have emerged as critical players in cardiovascular biology. In particular, miR-146a-5p is recognised as an important negative regulator of inflammation. This study aims to evaluate the prognostic role and biological effect of functional MIR146A polymorphisms, rs2431697 and rs2910164, in non-valvular atrial fibrillation (AF) patients under oral anticoagulation. We studied 901 patients with permanent/paroxysmal AF stabilized for at least six months. Patients were followed-up for two years and adverse cardiovascular events (ACE) were recorded. In vitro studies were performed in monocytes from healthy homozygous for the two genotypes of rs2431697. Rs2910164 had no association with ACE. However, multivariate analysis (adjusted by CHA2DS2–VASc score) revealed that rs2431697TT was associated with adverse cardiovascular events [HR: 1.64 (1.09–2.47); p=0.017]. The predictive value of usefulness of the CHA2DS2–VASc+IL6+rs2431697 for predicting ACE, was statistically better than that predicted by CHA2DS2–VASc+IL6. Functional studies showed that after 24 hours incubation, monocytes from CC individuals showed a 65 % increase in miR-146a-5p levels, while TT individuals only showed a 28 % increase. Indeed, after 24 hours of LPS activation, TT monocytes showed a higher increase in IL6 mRNA expression than CC (52 % vs 26 %). Our study established MIR146A rs2431697 as a prognostic biomarker for ACE in anticoagulated AF patients. These data suggest that TT individuals, when submitted to an inflammatory stress, may be prone to a highest pro-inflammatory state due, in part, to lower levels of miR-146a-5p.


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