Combined effect of pantoprazole and mesenchymal stem cells on experimentally induced gastric ulcer: implication of oxidative stress, inflammation and apoptosis pathways.

Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor ß1 (TGF-ß1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.

The Diagnostic Utility of Natural Killer Cell Subsets in Deep Vein Thrombosis.

Background: Natural killer (NK) cells are important components of adaptive and innate immune responses. NK cell subsets have different functions and may play a role in vascular disorders. This study aimed to evaluate the proportions of NK cells and their subsets to determine whether they can be used as markers of venous thrombosis and to identify whether there was a link between NK cell proportion and citrullinated histone (H3) levels. Patients and Methods: This study included 100 participants divided into Group I (n=50, patients with deep venous thrombosis (DVT)) and Group II (n=50, age- and sex-matched healthy controls). Group I was further categorized into Group Ia (n=25, patients with acute DVT) and Group Ib (n=25, patients with chronic DVT). The proportions of NK cells and their subsets were evaluated by flow cytometry using CD3/CD16/CD56. The levels of citrullinated histones (H3) were estimated using enzyme-linked immunosorbent assay (ELISA). Results: Compared to the control group, DVT patients had a significantly lower proportion of (CD56 dim/CD16+) NK cells, a significantly higher proportion of (CD56-/CD16+) NK cells and a high level of citrullinated histone (H3). Conclusion: NK cell subsets and citrullinated histone (H3) could be used as markers for DVT and as targets for therapeutic drugs to inhibit the formation or progression of thrombosis.

Assessment of the Antitumor Potentiality of Newly Designed Steroid Derivatives: Pre-Clinical Study.

Cancer is recognized as one of the most prevalent contributors to mortality in several nations and it remains one of the common health issues globally. In particular, hepatocellular carcinoma (HCC) has become a public health problem along with the increase of hepatitis B (HBV) and hepatitis C (HCV) virus infections. Based on this fact, our study goaled to synthesize newly hybrid drugs containing heterocyclic rings incorporated to steroid moiety and to examine the potential antitumor activity of the newly designed heterosteroid derivatives against HCC induced in animal model. Several heterocyclic steroids were synthesized 2-7 and confirmed via the analytical and spectral data (IR, 1H NMR13C NMR and Mass spectroscopy). Compounds 3, 4, and 5 were chosen to be investigated as anticancer agents in HCC rat model by means of validated biomarkers (alfa -fetoprotein, endoglin, lipocali-2 and heat shock protein-70). Following administration of compounds 3, 4 or 5, availability of the active tumor marker molecules was significantly dropped and a substantial decrease of the angiogenic and inflammatory mediators was also evident. These findings were supported by the histological examination of liver tissue. Taken together, this study indicates the potential anticancer activity of the newly synthesized heterosteroid derivatives against HCC in vivo. The antitumor activity of these compounds was likely attributable to modulating some signal transduction pathways involved in tumorigenesis, angiogenesis and inflammation.

Cytotoxic and genotoxic effects of arsenic on erythrocytes of Oryzias latipes: Bioremediation using Spirulina platensis.

BACKGROUND: Exposure to the environmental pollutants poses a serious threat to aquatic organism. The arsenic exposure in fish increases the risk of developing serious alterations from embryo to adult. OBJECTIVES: The present investigation was done to study the toxic effects of heavy metal arsenic [As(III)] on medaka (Oryzias latipes). Morphological alterations, apoptosis, nuclear abnormalities, and genotoxic biomarkers in erythrocytes were used to determine the stress caused by arsenic (As) exposure. METHODS: Medaka was exposed to As for 15 days at two toxic sublethal concentrations (7 ppm and 10 ppm) in combination with Spirulina platensis (SP) treatment as antioxidant algae at 200 mg/L. RESULTS: Results were consistent with a previous study results on tilapia. Exposure of medaka to As resulted in a dose-dependent increase in most the biomarkers used in the current study. Fish exposed to10 ppm As showed highest level of DNA damage. For the first time to our knowledge, using SP to counter the As toxicity in medaka, DNA damage restored to control levels. CONCLUSION: Accordingly, those results suggests that SP can protect medaka in aquaculture against As-induced damage by its ability as reactive oxygen species (ROS) reducer, antioxidant role, and DNA damage scavenger.

Environmental pollution and toxic substances: Cellular apoptosis as a key parameter in a sensible model like fish.

The industrial wastes, sewage effluents, agricultural run-off and decomposition of biological waste may cause high environmental concentration of chemicals that can interfere with the cell cycle activating the programmed process of cells death (apoptosis). In order to provide a detailed understanding of environmental pollutants-induced apoptosis, here we reviewed the current knowledge on the interactions of environmental chemicals and programmed cell death. Metals (aluminum, arsenic, cadmium, chromium, cobalt, zinc, copper, mercury and silver) as well as other chemicals including bleached kraft pulp mill effluent (BKME), persistent organic pollutants (POPs), and pesticides (organo-phosphated, organo-chlorinated, carbamates, phyretroids and biopesticides) were evaluated in relation to apoptotic pathways, heat shock proteins and metallothioneins. Although research performed over the past decades has improved our understanding of processes involved in apoptosis in fish, yet there is lack of knowledge on associations between environmental pollutants and apoptosis. Thus, this review could be useful tool to study the cytotoxic/apoptotic effects of different pollutants in fish species.

Hepatotoxic responses of 4-nonylphenol on African catfish (Clarias gariepinus): antixoidant and histochemical biomarkers.

4-Nonylphenol (NP) toxicity in fish attracts much attention due to its ability in targeting several organs; however, the researches regarding its potential hepatotoxicity are conflicting and still require further investigation. Therefore, the objective of this study is to focus on this issue from the histophysiological point of view using NP intoxicated African catfish (Clarias gariepinus) as a model of hepatotoxicity. Twelve adult fish (6 per group) were divided into two groups; the first was considered as a control and the second was exposed to NP dissolved in water at a dose of 0.1 mg/kg BW for 3 weeks. A significant reduction in the hepatic alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels was observed in NP-exposed fish. Concerning the oxidant/antioxidant balance, a significant depletion in superoxide dismutase, catalase, and glutathione peroxidase was found along with a significant elevation in total peroxide and malondialdhyde. The histopathological examination of the hepatic tissues revealed that NP had marked hepatotoxic effects including hepatitis, centrilobular and focal hydropic and fatty degeneration, fatty change (steatosis), hepatic coagulative necrosis, and nuclear alterations in addition to apoptosis of hepatocytes and necrosis of endothelial cells. Depletion of the glycogen and increased in pigments (lipofuscin and hemosiderin) content in the hepatocytes were also recorded. Hemosiderosis and proliferation of the connective tissue around the blood vessels and branches of bile ducts and in the portal areas were also observed. In light of these findings, it was concluded that NP has a well-defined hepatotoxic impact paving the road towards other studies to investigate other detrimental cyto-physiological influences of this aquatic pollutant.

Biochemical and molecular evidences for the antitumor potential of Ginkgo biloba leaves extract in rodents.

Hepatocellular carcinoma (HCC) is one of the deadliest primary cancers, with a 5-year survival rate of 10% or less. This study was undertaken to elucidate the underlying biochemical and molecular mechanisms in favor of N-nitrosodiethylamine-induced hepatocellular carcinoma. Furthermore, the aim of this work was extended to explore the efficacy of Ginkgo biloba leaves extract in deterioration of HCC in rats. In the current study, HCC group experienced significant downregulation of ING-3 gene expression and upregulation of Foxp-1 gene expression in liver. Treatment of HCC groups with Ginkgo biloba leaves extract resulted in upregulation of ING-3 and downregulation of Foxp-1 gene expression in liver. In addition, there was significant increase in serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and glypican-3 (GPC-3) levels in HCC group versus the negative control group. In contrast, the groups with HCC subjected to either high or low dose of Ginkgo biloba leaves extract elicited significant reduction (P<0.05) of AFP, CEA and GPC-3 in serum compared to the untreated HCC rats. Besides, histological examination of liver tissue sections of rats in HCC group revealed typical anaplasia. Interestingly, treatment with Ginkgo biloba leaves extract elicited marked improvement in the histological feature of liver tissue in HCC groups. In conclusion, this research indicated that the carcinogenic potency of N-nitrosodiethylamine targeted multiple systems on the cellular and molecular levels. In addition, the results of the current study shed light on the promising anticancer activity of Ginkgo biloba leaves extract in treatment of hepatocellular carcinoma induced chemically in the experimental model through its apoptotic and antiproliferative properties.