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The current study was aimed to investigate the involvement of endoplasmic reticulum stress (ERS)-mediated protein kinase R-like endoplasmic reticulum kinase (PERK) signaling in advanced glycation end products (AGEs)-exacerbated coronary microvascular dysfunctions (CMD) in non-obstructive coronary artery disease (NoCAD).

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mice were used as NoCAD animal model which were exposed to AGEs by intraperitoneal injections. Animal CMD was evaluated by coronary flow velocity reserve (CFVR). A viral vector carrying perk-siRNA was used to silence PERK in vivo and in vitro studies. Cell apoptosis was detected by TUNEL. Immunofluorescent staining was used to assess CD42c-positive cell number in cardiac sections and NFATc4 translocation in CMECs. Real-time PCR and Western blotting were used to evaluate the gene expression levels. Cytokine and AGEs concentrations were determined by ELISA. Enzymatic activity of CaN was measured by a colorimetric method. A registered cross sectional study consisted of 77 patients dian CMECs. IMR values increased significantly in NoCAD patients complicated with diabetes, which were significantly and positively correlated with serum AGEs concentrations.

Diabetes was associated with CMD in NoCAD. AGEs fostered in diabetes exacerbated CMD by activating ERS-mediated PERK/CaN/NFATc4 signaling in CMECs. IMR values increased significantly in NoCAD patients complicated with diabetes, which were significantly and positively correlated with serum AGEs concentrations.Algae are omnipresent in all seas and oceans, which make thema target for many applications such as bio-fertilizers, fish feeding and removal of heavy metals. In the present study, different algal species were examined as sustainable alternatives substrates for PHA production by Halomonas sp. Several media simulations were utilized to achieve high polymer productivity. The maximum poly(3-hydroxybutyrate) (PHB) concentrations were determined by using Corallina mediterranea hydrolysates as a carbon and nitrogen source. The isolates Halomonas pacifica ASL10 and Halomonas salifodiane ASL11 were found to be able to produce PHA by 67 % wt and 63 % wt CDW, respectively. PHB nanoparticles (NPs) had high zeta potential values and small particle sizes. These properties make it suitable for several drug delivery and pharmaceutical applications. Interestingly, NPs showed a potent antibacterial activity against several reference strains. The antibacterial efficacy of PHA-NPs has not been previously studied, thus this study opens a promising use of PHA-NPs.A novel glucose oxidase (GOD)-perhydrolase-in situ chemical oxidation (ISCO) cascade reaction system was designed, optimized, and verified the operation feasibility in this research. Among the determined four perhydrolases, acyltransferase from Mycobacterium smegmatis (MsAcT) displayed the highest specific activity for perhydrolysis reaction (76.4 U/mg) and the lowest Km value to hydrogen peroxide (13.9 mmol/L). GOD-MsAcT cascade reaction system also displayed high catalytic efficiency. Under the optimal parameters (501 activity unit ratio of GOD to MsAcT, pH 8.0, 50 mmol/L of β-d-glucose, and 15 mmol/L of glyceryl triacetate), the melanin decolorization rate using GOD-MsAcT-ISCO cascade reaction system reached 86.8 %. Kinetics of GOD-MsAcT-ISCO cascade reaction system for melanin decolorization fitted the kinetic model of Boltzmann sigmoid. As a substitutive skin whitening technology, GOD-MsAcT-ISCO cascade reaction system displayed an excellent application prospect.Ganoderic acids (GAs) produced by Ganoderma are a type of lanostane-type triterpenoids with anticancer and antimetastatic activities; however, low production of GAs limits its wide application. In this study, a novel strategy by promoting sporulation of Ganoderma was developed to increase GA production. First, a high-spore producing Ganoderma strain G. 260125 was obtained from dikaryotic strain CGMCC 5.0026, and the sporulation-specific gene of this strain exhibits a higher transcription level than CGMCC 5.0026. Then, the effect of promoting sporulation on GA content was investigated. The maximum ganoderic acid (GA)-T, GA-Mk, and GA-Me contents in G. 260125 in shake flasks were 358.97, 78.32, and 12.75 μg/100 mg dry weight, respectively, which were 3.42, 2.91, and 1.73 times higher than those obtained in CGMCC 5.0026. selleck kinase inhibitor Moreover, total and individual GA contents in spores were significantly higher than those in liquid static culture. Both concentrations of intermediates and transcription levels of GA biosynthetic genes also improved in G. 260125 during fermentation compared with those in CGMCC 5.0026. For scaling-up experiments, GA-T, GA-Me, and GA-Mk production in G. 260125 improved by 2.2-, 2.6-, and 2.1-fold compared with those in CGMCC 5.0026. In addition, the effectiveness of the developed strategy was also confirmed in three different Ganoderma strains. This work illustrated that promoting sporulation efficiently improves GA production in liquid static cultures of Ganoderma.Soluble expression of recombinant proteins in E. coli is often done by translocation of the product across the inner membrane (IM) into the periplasm, where it is retained by the outer membrane (OM). While the integrity of the IM is strongly coupled to viability and impurity release, a decrease in OM integrity (corresponding to increased "leakiness") leads to accumulation of product in the extracellular space, strongly impacting the downstream process. Whether leakiness is desired or not, differential monitoring and control of IM and OM integrity are necessary for an efficient E. coli bioprocess in compliance with the guidelines of Quality by Design and Process Analytical Technology. In this review, we give an overview of relevant monitoring tools, summarize the research on factors affecting E. coli membrane integrity and provide a brief discussion on how the available monitoring technology can be implemented in real-time control of E. coli cultivations.Cancer immunotherapy is a promising intervention to fight against this global health problem. In particular targeting immune checkpoints, such as cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed-death protein 1 (PD-1), by specific monoclonal antibodies is a current treatment for many malignances. A possible innovation in this field is based on the induction of humoral responses in the host by suppressing the effects of such immune checkpoints and as consequence favoring the activation of cellular immunity against the tumor cells. In this study, chimeric protein comprising the B subunit of Escherichia coli heat-labile enterotoxin as carrier and the extracellular domain of CTLA-4 (LTB-CTLA4) was produced in Nicotiana benthamiana by transient expression. The recombinant protein was accumulated up to 1.29 μg/g of leaves fresh weight on 4 day-post-infiltration. The integrity of the plant-made LTB-CTLA4 antigen was confirmed by western blot analysis and ELISA. Immunogenicity of the plant-made LTB-CTLA4 was assessed in BALB/c mice and the results showed that humoral responses were induced against both the LTB and CTLA-4 moieties.