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The present study was aimed to compare and evaluate the impacts of supplemented diets with different yeast hydrolysate (YH) levels on growth performance, body composition, hematological characteristics, antioxidant enzyme activities, and non-specific immunity (intestinal cytokines) of juvenile Nile tilapia (Oreochromis niloticus). Three isonitrogenous (protein, 33%) and isolipidic (lipid, 6%) experimental diets supplemented graded levels of YH (0% for control; 1% and 3% as tested diets) were fed to juvenile Nile tilapia. A total of 240 fish with initial body weight averaging 3.5 ± 0.02 g were randomly divided into three groups with four replicates per group and 20 fish for each replicate. For apparent satiation, the fish were fed twice daily during eight weeks. The results showed no significant difference in survival among all treatments. The fish fed the diet containing 1% yeast hydrolysate had significantly elevated weight gain (WG), specific growth rate (SGR), protein efficiency ratio (PER) compared to the control group and lower feed conversion ratio (FCR). The fish fed 1% and 3% YH showed higher glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) activity and a significantly lower malondialdehyde (MDA) level in the liver than the control group, indicating enhancement of the anti-oxidant status. Selleck BAY 43-9006 Serum lysozyme activity was significantly increased in the diet having 1% and 3% yeast hydrolysate supplementation groups, suggesting an improvement influence on the non-specific immune response. The expression of IL-1β, IL-10, TNF-α, TGF-β2, ALP and TLR2 was significantly elevated in fish fed the diet containing 1% YH. In conclusion, dietary supplementation with 1% yeast hydrolysate improves growth performance, and feed utilization enhances the antioxidant status and exerts an adequate stimulus on the non-specific immunity (intestinal cytokines) of Nile tilapia. Human cytomegalovirus (HCMV) infection causes severe illness in newborns and immunocompromised patients. Since treatment options are limited there is an unmet need for new therapeutic approaches. Defensins are cationic peptides, produced by various human tissues, which serve as antimicrobial effectors of the immune system. Furthermore, some defensins are proteolytically cleaved, resulting in the generation of smaller fragments with increased activity. Together, this led us to hypothesize that defensin-derived peptides are natural human inhibitors of virus infection with low toxicity. link2 We screened several human defensin HNP4- and HD5-derived peptides and found HD5(1-9) to be antiviral without toxicity at high concentrations. HD5(1-9) inhibited HCMV cellular attachment and thereby entry and was active against primary as well as a multiresistant HCMV isolate. Moreover, cysteine and arginine residues were identified to mediate the antiviral activity of HD5(1-9). Altogether, defensin-derived peptides, in particular HD5(1-9), qualify as promising candidates for further development as a novel class of HCMV entry inhibitors. V.Neuronal growth regulator 1 (NEGR1), a member of the immunoglobulin superfamily cell adhesion molecule subgroup IgLON, has been involved in neuronal growth and connectivity. Genetic variants, in or near the NEGR1 locus, have been associated with obesity and, more recently, with learning difficulties, intellectual disability, and psychiatric disorders. Here, we described the only second report of NEGR1 gene disruption in 1p31.1 microdeletion in two patients. Patient 1 is a 14-year-old female with neurological and psychiatric features present also in her family. Patient 2 is a 5-month-old infant showing global hypotonia as unique neurological features till now. This patient also carries 7p22.1 duplication, of paternal origin, that could be responsible for some malformations present in the child. We hypothesize a role of NEGR1 in producing the phenotype of our patients and compare them with other cases previously reported in the literature and DECIPHER database to better identify a possible genotype-phenotype correlation. An elaborated phytochemical study on the fresh fruits of Terminalia chebula var. tomentella (Combretaceae) led to the isolation of five new lignans, including three tetrahydrofuran (1-3) and two furofuran (4 and 5) derivatives, namely termitomenins A-E (1-5), along with 10 known ones. All of them were obtained from the titled plant for the first time. Their structures were determined by extensive spectroscopic analysis, including 1D/2D NMR, MS, UV, IR, electronic circular dichroism (ECD), time-dependent density functional theory (TDDFT) calculation of ECD spectra, and single crystal X-ray diffraction in case of 3. Compounds 1-15 exhibited certain anti-inflammatory activities. Interestingly, compounds 6 (IC50 = 18.17 ± 0.57  μM) and 7 (IC50 = 13.66 ± 0.38 μM) which contain an aldehyde group displayed stronger NO inhibitory activity than the positive control L-NMMA (IC50 = 42.34 ± 0.66 μM). Four polyacetylenic glycosides, three of which are new, together with two known flavonoids were isolated from the methanol extract of the aerial parts of Launaea capitate, designated bidensyneoside A1 (1), 6´-O-acetyl-bidensyneoside A1 (2), bidensyneoside E (3), bidensyneoside F (4), luteolin (5) and luteolin-7-glucoside (6) also known as cynaroside. Their structures were elucidated by comprehensive analysis of 1D, 2D-NMR and HR-MS data. The absolute configuration of bidensyneosides was determined by Mosher ester analysis and the optical rotation values. The isolated compounds were tested against biofilm formation of Staphylococcus aureus as well as against several pathogens including Gram-positive bacteria, Gram-negative bacteria, fungi and yeasts. Furthermore, they were tested for their cytotoxicity against two cancer cell lines L929 and KB-3-1. Compound 4 showed moderate inhibition of S. aureus biofilm formation with 30% and 25% at 256 and 128 μg/mL, respectively, while compounds 1 and 5 showed weak inhibition with 20% at 256 μg/mL. Compound 5 showed moderate cytotoxicity against both cell lines L929 and KB-3-1, with IC50 values of 18 μg/mL. BACKGROUND Coronary artery disease (CAD) is the most common cause of heart failure (HF) in developed countries. The aim of this study is to elucidate the mechanisms of reduction of arrhythmias after LCZ696 therapy in a myocardial infarction (MI)-HF rabbit model. METHODS AND RESULTS Chronic MI with HF rabbits were divided into three groups placebo control, valsartan 30 mg/day and LCZ696 60 mg/day. After 4-week therapy, electrophysiological study and dual voltage-calcium optical mapping study were performed. The LCZ696 group had significant better left ventricular ejection fraction and lower ventricular tachyarrhythmia (VA) inducibility than the valsartan and placebo groups. The most common VA pattern was one or two ectopic beats originated from the peri-infarct areas followed by reentrant beats surrounding phase singularity points. link3 Compared to the valsartan and placebo groups, the LCZ696 group had significantly shorter action potential duration, shorter intracellular calcium tau constant, faster conduction velocity and shorter pacing cycle length to induce arrhythmogenic alternans. LCZ696 therapy reduced the phosphorylated calmodulin-dependent protein kinase II (CaMKII-p) expression. CONCLUSIONS In a rabbit model with chronic MI and HF, LCZ696 therapy ameliorated post-infarct heart function impairment, electrophysiological remodeling and altered CaMKII-p expression, leading to reduced VA inducibility. ETHNOPHARMACOLOGICAL RELEVANCE Cuphea is the largest genus of the Lythraceae family. It is popularly known as "sete-sangrias" in Brazil used in folk medicine as a diuretic, antipyretic, anti-inflammatory, laxative and antihypertensive agent. The raw material of Cuphea has shown promising results in the production of fitotherapics, which are chemically characterized by quercetin core flavonoids. AIMS OF THE STUDY Present work aims to investigate the chemical composition of Cuphea calophylla, Cuphea carthagenensis, Cuphea glutinosa and Cuphea racemosa by UHPLC-MS using ESI-Q-TOF, and also to investigate the inhibition of angiotensin-converting enzyme (ACE) in vitro. MATERIALS AND METHODS Leaves extraction was conducted by an ultrasound-assisted system under the following conditions 40% ethanol, particle size ≤180 μm, plantsolvent ratio 120 (w/v) for 30 min. The leaf extracts were analyzed by UHPLC-MS positive mode ionization. For the inhibition of ACE, the leaf extracts used were obtained from different Cuphea species collected from several regions of Rio Grande do Sul (Brazil). RESULTS In total 26 polyphenolic compounds were proposed, which were mostly derived from quercetin, myricetin, and kaempferol. Of these compounds, ten are described in the genus for the first time. The ACE-inhibiting activities are presented in descending order miquelianin (32.41%), C. glutinosa 1 (31.66%), C. glutinosa 5 (26.32%) and C. carthagenensis 1 (26.12%). CONCLUSION The obtained results suggest that the ACE-inhibiting potential may be increased by the interactions among the different phytoconstituents present in the crude extract. These results corroborate with the popular usage of Cuphea genus as diuretic and antihypertensive agents in folk medicine. ETHNOPHARMACOLOGICAL RELEVANCE Asteris Radix et Rhizoma (AR) refers to the roots and rhizomes of Aster tataricus L., which is widely distributed throughout East Asia. AR has been consumed as a traditional medicine in Korea, Japan and China for the treatment of urologic symptoms. To date, however, the therapeutic effect of AR on benign prostatic hyperplasia (BPH) has not been investigated. AIM OF THE STUDY The present study evaluated the therapeutic effects of AR on a testosterone-induced BPH rats. MATERIALS AND METHODS We induced BPH to rats by subcutaneous injections (s.c) of testosterone propionate (TP) daily for four weeks. Rats were also administered daily oral gavage of AR (150 mg/kg) or vehicle. After four weeks of induction, all animals were euthanized humanely and their prostate glands were removed, weighed and processed for further analysis, including histopathological examination, real-time PCR, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and Western blot analysis. RESULTS Administration of AR to TP-induced BPH rats considerably reduced prostate weight and concentrations of serum testosterone and prostate dihydrotestosterone (DHT). Epithelial thickness and expression of proliferating cell nuclear antigen (PCNA) were markedly suppressed by AR-treatment in the rats. Furthermore, the expression of the B-cell lymphoma 2 (Bcl-2) were reduced and expression of the Bcl-2-associated X protein (Bax) increased, resulting in significant reduction in Bcl-2/Bax ratio. In addition, AR decreased the level of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were reduced by AR treatment in a TP-induced BPH rat model. CONCLUSIONS AR alleviates BPH by promoting apoptosis and suppressing inflammation, indicating that AR may be used clinically to treat BPH accompanied by inflammation.

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