Protective effects of nebivolol against cold restraint stress-induced gastric ulcer in rats: role of NO, HO-1, and COX-1,2

Nebivolol, a β(1)-adrenoceptor antagonist, exhibits vasodilatory and anti-oxidative properties that rendering it attractive candidate for protecting against gastric ulcer. The aim of this study therefore is to evaluate the protective effects of nebivolol against cold restraint stress (CRS)-induced gastric ulcer in rats. Rats were restrained, and maintained at 4°C for 3 h. Nebivolol (5 mg/kg, p.o.) was suspended in 0.5% aqueous solution of carboxymethyl cellulose and was administered 30 min before CRS. Nebivolol exhibited gastroprotective effects as evidenced by significant decreases in ulcer index as well as free and total acid output, and pepsin activity in gastric juice in addition to gastric mucosal malondialdehyde concentration, with concomitant increases in gastric juice pH and mucin concentration along with gastric mucosal reduced glutathione and nitric oxide (NO) concentrations compared with CRS rats. Moreover, immunohistochemical analysis demonstrated that nebivolol treatment markedly enhanced heme oxygenase-1 as well as cyclooxygenase-1 and cyclooxygenase-2 expressions. The protective effects of nebivolol were confirmed by gastric histopathological examination. Pretreatment with N(ω)-nitro-L-arginine, a NO synthase inhibitor, partly altered the protection afforded by nebivolol. In conclusion, nebivolol protected rats' gastric mucosa against CRS-induced gastric ulceration possibly through anti-oxidant activity, enhancement of gastric mucosal barrier and reduction in acid secretory parameters.     

Irisin immunohistochemistry in gastrointestinal system cancers

Cancer is the leading cause of morbidity and mortality worldwide. Some studies have shown that high heat kills cancer cells. Irisin is a protein involved in heat production by converting white into brown adipose tissue, but there is no information about how its expression changes in cancerous tissues. We used irisin antibody immunohistochemistry to investigate changes in irisin expression in gastrointestinal cancers compared to normal tissues. Irisin was found in human brain neuroglial cells, esophageal epithelial cells, esophageal epidermoid carcinoma, esophageal adenocarcinoma and neuroendocrine esophageal carcinoma, gastric glands, gastric adenosquamous carcinoma, gastric neuroendocrine carcinoma, gastric signet ring cell carcinoma, neutrophils in vascular tissues, intestinal glands of colon, colon adenocarcinoma, mucinous colon adenocarcinoma, hepatocytes, hepatocellular carcinoma, islets of Langerhans, exocrine pancreas, acinar cells and interlobular and interlobular ducts of normal pancreas, pancreatic ductal adenocarcinoma, and intra- and interlobular ducts of cancerous pancreatic tissue. Histoscores (area × intensity) indicated that irisin was increased significantly in gastrointestinal cancer tissues, except liver cancers. Our findings suggest that the relation of irisin to cancer warrants further investigation.     

Structures of new amphidinols with truncated polyhydroxyl chain and their membrane-permeabilizing activities

Two new homologues of amphidinols (AM14 and AM15) were isolated from the cultured dinoflagellate Amphidinium klebsii. The structures were elucidated on the basis of 2D NMR and collision-induced dissociation MS/MS and turned out to be closely related homologues of AM7. Their weak membrane-disrupting activity indicates that the hydrophobic polyene chain is essential for the potent biological activities. Structure-activity relationship for the polyhydroxyl part was then examined with use of AM homologues possessing various chain lengths, indicating that the pore size of the channel/lesion formed by AMs was not greatly affected by the length of the polyhydroxyl chain.     

Evidence for an early evolutionary emergence of γ-type carbonic anhydrases as components of mitochondrial respiratory complex I

Background  

The complexity of mitochondrial complex I (CI; NADH:ubiquinone oxidoreductase) has increased considerably relative to the homologous complex in bacteria. Comparative analyses of CI composition in animals, fungi and land plants/green algae suggest that novel components of mitochondrial CI include a set of 18 proteins common to all eukaryotes and a variable number of lineage-specific subunits. In plants and green algae, several purportedly plant-specific proteins homologous to γ-type carbonic anhydrases (γCA) have been identified as components of CI. However, relatively little is known about CI composition in the unicellular protists, the characterizations of which are essential to our understanding of CI evolution.     

Effects of <Emphasis Type="SmallCaps">l</Emphasis>-Canavanine and ozone on vascular reactivity in septicemic rats

Septicemia leads to oxidative stress with overproduction of reactive-oxygen species (ROS) and consumption of endogenous antioxidant enzymes. We tested a twofold hypothesis: (1) does oxidative stress (OxS) induced by sepsis acting alone or in concert with augmented inflammatory processes contributes to sepsis-related vascular dysfunction, and, (2) whether ozone (O₃) and l-canavanine (CAV) mitigate the negative impact of the aforementioned phenomena. We investigated the relative impact of treatment with CAV and/or O₃ on vascular OxS associated vascular functional changes in septicemic rats. For this study, 60 male Sprague–Dawley rats were used and divided into six experimental groups (n = 10): control group (C), sham-operated (Sham), septicemic rats (S), S rats treated with CAV (100 mg/kg. i.p; S + CAV), S rats treated with O₃ (1.2 mg/kg, i.p.; S + O₃) and S rats treated with both O₃ and CAV (S + O₃ + CAV). After 22 h, the mean arterial blood pressure (MAP), the aortic ring vascular reactivity to phenylephrine, abdominal aortic blood flow (AABF), serum tumor necrosis factor-α (TNF-α) and plasma nitrite/nitrate (NOx) concentration were measured. In addition, hepatic antioxidant enzyme activities sodium dismutase (SOD) and glutathione peroxidase (GSH-Px) were estimated. Septicemia caused significant elevation of serum TNF-α (p < 0.001) and plasma NOx (p < 0.001) and significant (p < 0.001) reduction of AABF (p < 0.001), aortic vascular response to phenylephrine (p < 0.001), MAP (p < 0.001) and hepatic SOD and GSH-Px activity (p < 0.001) compared with the C group, while treatment with O₃ and/or CAV induced significant amelioration of all those increases. Abnormalities were attenuated to a similar extent with treatment with both O₃ and CAV. These results suggested that concomitant administration of O₃ and CAV alleviated the compromised vascular reactivity in septicemic conditions and prevent its progression into septic shock compared with each alone.     

Fluoride in Commercially Important Bivalves from Polluted Sites along the Egyptian Sea Coasts: Relation to Human Health Risk

The human health risk of fluoride from the consumption of four commercial bivalve species collected from contaminated sites along the Egyptian Sea coasts was assessed. The fluoride concentration in soft and shell tissues of fresh bivalve species (Callista florida, Paphia textile, Donax vittatus and Anadara diluvii) was determined. The predicted human health risk of fluoride from the consumption of the samples was studied by applying the calculations of estimated daily intake and hazard quotient for toddlers' (1.84–3.99 mg/kg/day and 15.1–32.7, respectively) and adults' (1.22–2.64 mg/kg/day and 10.0–21.7, respectively) ingestion. The fluoride contents in soft and shell tissues of bivalve samples along all the sampling locations were 0.38–0.64 and 0.56–0.69 mg/g with averages 0.50 ± 0.10 and 0.62 ± 0.05 mg/g, respectively. ANOVA and multiple regression analyses reflected that the accumulation of fluoride in bivalve species was influenced by the dimensions and weight of the bivalve species. The average calculated estimation of the daily intake of fluoride for toddlers and adults ingesting the bivalve species exceeded the lowest-observed-adverse-effect level of skeletal effects' value (LOAEL; 0.25 mg fluoride/kg/day). The evaluated hazard quotient values also pointed to the human health hazards that may be caused by bivalve consumption.     

Leishmania major: solid phase radioimmunoassay for antibody detection in human cutaneous leishmaniasis

A radioimmunoassay for the quantitative determination of antileishmanial antibody in sera from patients suffering from cutaneous leishmaniasis was developed. The assay, using as antigen either the soluble fraction from freeze-thawed sonicated Leishmania major (LRC-L137) promastigotes or a carbohydrate-lipid containing fraction obtained by extraction with hexane-isopropanol, was shown to be sensitive and reproducible. The sera of 95 patients were examined. These were from patients with cutaneous leishmaniasis (26 from the Jordan Valley and 13 from Sinai), kala-azar (9), malaria (24), schistosomiasis (10), toxoplasmosis (5), and leprosy (8); controls were 37 normal human sera. No significant antigen dependent differences were observed using sera from cutaneous leishmaniasis patients, although differences in the immunological response were observed between the two populations of these patients. Antileishmanial activity was not detected in sera from patients with malaria, schistosomiasis, or toxoplasmosis. Although sera from leprosy patients crossreacted with the carbohydrate-lipid containing fraction, it was nevertheless more strain specific than freeze thawed sonicated L. major.     

Therapeutic properties and molecular docking study of some phenolic compounds as anti-human lung cancer potential: A biochemical approach

Chloroxine (5,7-dichloro-8-hydroxyquinoline) is a molecule utilized in some shampoos for the therapy of seborrheic dermatitis of the scalp and dandruff. In this study, we investigated the inhibition effects of 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate compounds on the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA Reductase) and urease enzymes. We have obtained results for the HMG-CoA Reductase and urease enzymes at the micromolar level. In our study, inhibition result of 5,7-dichloro-8-hydroxyquinoline and Methyl 3,4,5-trihydroxybenzoate on HMG-CoA reductase showed lower values 2.28 ± 0.78 and 33.25 ± 5.04 µg/ml, respectively. Additionally, inhibition result of 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate on urease showed lower values 6.18 ± 1.38 and 8.51 ± 1.35 µg/ml, respectively. Molecular docking calculations were made for their biological activities were compared. In the present work, the structures of the related compounds ( 1 and 2 ) were drawn using Gaussian 09 software and done geometry optimization at DFT/B3LYP/6-31G* basis set with aforementioned program. Cytotoxicity potential of these compounds against human lung cancer demonstrated that these compounds had good cytotoxic effects. Both compounds significantly decreased lung cell viability from low doses. In addition, 100 µM dose of all compounds caused significant reductions in lung cell viability. In general, we can say that of the two tested compounds, 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate have cytotoxic effects in all cell types, and this effect is particularly strong in lung cells. Activities were performed at concentrations of 10, 20, 50, 70, and 100 µl and we achieved good results. Lung cell viability (%) value was better at 100 µl concentration and IC₅₀ of them were 54.28 and 48.05 µM.