Anticonvulsive Effect of Glucosyl Xanthone Mangiferin on Pentylenetetrazol (PTZ)-Induced Seizure-Provoked Mice.

Anxiety and depression are major side effects induced by currently available antiepileptic drugs; apart from this, they also diminish intelligence and language skills which cause hepatic failure, anemia, etc. Hence, in this study, we assessed antiepileptic effect of a phytochemical mangiferin. Epilepsy, a prevalent non communicable neurological disorder, affects infants and older population throughout the world. Epilepsy-induced comorbidities are more severe and if not treated cautiously lead to disability and even worse cases, mortality. The onset and duration of convulsion were observed. Seizure severity score was assessed by provoking kindling with 35 mg/kg PTZ. Prooxidants and antioxidants were measured to assess the antioxidant effect of mangiferin. Inflammatory markers were measured to determine the anti-inflammatory effect of mangiferin. The levels of neurotransmitters and ATPases were quantified to evaluate the neuroprotective effect of mangiferin. Mangiferin significantly decreased the onset and duration convulsion. It also decreased the seizure severity score, locomotor activity, and immobilization effectively. The excitatory neurotransmitter was reduced, and inhibitory neurotransmitter was increased in mice treated with mangiferin. Overall, our results confirm that mangiferin efficiently protects mice from PTZ-induced seizures. It can be subjected to further research to be prescribed as a potent antiepileptic drug.

Effect of Dezocine on the Ratio of Th1/Th2 Cytokines in Patients Receiving Postoperative Analgesia Following Laparoscopic Radical Gastrectomy: A Prospective Randomised Study.

PURPOSE: To evaluate the effect of dezocine on the postoperative ratio of Th1/Th2 cytokines in patients undergoing laparoscopic radical gastrectomy. PATIENTS AND METHODS: Sixty patients undergoing laparoscopic radical gastrectomy were randomly divided into two groups (n=30): dezocine group (Group D) and sufentanil group (Group S). They received patient-controlled intravenous analgesia (PCIA) after the operation with either dezocine 0.8 mg/kg (Group D) or sufentanil 2 µg/kg (Group S). Both groups also received ondansetron 8 mg diluted to 100 mL with saline. The primary outcome was the Th1/Th2 cytokines ratio at predetermined intervals, 30 min before the induction of general anaesthesia and 0, 12, 24 and 48 h after surgery. The secondary endpoints were patients' pain scores, measured on a visual analogue scale (VAS) at predetermined intervals (0, 12, 24 and 48 h after surgery), and side effects at follow-up 48 h after surgery. RESULTS: The Th1/Th2 cytokines ratio in Group D was significantly higher than Group S (P<0.05) 12, 24 and 48 h after the operation. There were no significant differences in VAS pain scores between groups at 0, 12, 24 and 48 h after surgery (P>0.05). Compared to Group S, the incidence of postoperative nausea, vomiting and lethargy was significantly lower in Group D (P<0.05). CONCLUSION: Dezocine increases the ratio of Th1/Th2 cytokines, relieves postoperative pain and causes fewer side effects in patients undergoing laparoscopic radical gastrectomy.

Neuroprotective effects of protocatechuic acid on sodium arsenate induced toxicity in mice: Role of oxidative stress, inflammation, and apoptosis.

Arsenic is a toxic metalloid abundantly found in nature and used in many industries. Consumption of contaminated water mainly results in human exposure to arsenic. Toxicity (arsenicosis) resulting from arsenic exposure causes cerebral neurodegeneration. Protocatechuic acid (PCA), a phenol derived from edible plants, has antioxidant properties. The present study investigated the neuroprotective potential of PCA against arsenic-induced neurotoxicity in mice. Male Swiss albino mice were divided into four groups: (i) orally administered physiological saline, (ii) orally administered 100 mg/kg PCA, (iii) orally administered 5 mg/kg NaAsO2, and (iv) orally administered 100 mg/kg PCA 120 min prior to oral administration of 5 mg/kg NaAsO2. Each group received its respective treatment for 1 week, after which cortical tissues from each group were analyzed for various parameters of oxidative stress, proinflammatory cytokines, apoptosis-related proteins, and changes in histopathology. NaAsO2-treatment resulted in a significant increase in lipid peroxidation (LPO), inducible nitric oxide synthetase (iNOs), and NO levels, with a decrease in the levels of both enzymatic (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and non-enzymatic (glutathione) antioxidant markers. Arsenic increased proinflammatory cytokine (tumor necrosis factor-α and interleukin-1ß) levels, enhanced caspase-3 and Bax expression, and reduced Bcl-2 expression. Furthermore, arsenic-exposure in mice decreased significantly acetylcholinesterase activity and brain-derived neurotrophic factor level in the cerebral cortex. Histopathological examination revealed changes in nerve cell cyto-architecture and distribution in arsenic-exposed brain tissue sections. PCA treatment before arsenic administration resulted in a positive shift in the oxidative stress and cytokine levels with decreased levels of LPO, iNOS, and NO. PCA pre-treatment considerably attenuated arsenic-associated histopathological changes in murine brain tissue. This study suggested that the presence of PCA may be responsible for the prevention of arsenic-induced neurotoxicity.

Endomorphin-2 Analog Inhibits the Growth of DLD-1 and RKO Human Colon Cancer Cells by Inducing Cell Apoptosis.

BACKGROUND In developed countries, colon cancer is a leading cause of cancer-associated mortality. Dietary changes have resulted in an increased incidence of colon cancer in Asia. This study aimed to investigate the effects of the structural analog of endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2) on human colon cancer cells in vitro. MATERIAL AND METHODS Human DLD-1 and RKO colon cancer cells and CCD-18Co normal human colonic fibroblasts were treated with increasing doses of the structural analog of endomorphin-2. Cells underwent the MTT assay, fluorescence confocal flow cytometry, and Hoechst 33258 staining to investigate cell proliferation, the cell cycle, and apoptosis. Western blot was used to measure the expression levels of poly(ADP-ribose) polymerase-1 (PARP-1), cytochrome c, caspase-3, and caspase-9. The 2',7'-dichlorofluorescein diacetate (DCFH-DA) fluorescence method measured reactive oxygen species (ROS). RESULTS Cell proliferation of DLD-1 and RKO cells was inhibited by the endomorphin-2 analog in a dose-dependent manner, and a 100 µM dose reduced DLD-1 and RKO cell proliferation by 28% and 23%, respectively, at 72 h. Endomorphin-2 analog induced cell apoptosis and the generation of ROS, activated caspase-3 and caspase-9, and increased the levels of p53 and cytochrome c release, and down-regulated of Akt activation in DLD-1 and RKO cells in a dose-dependent manner. Treatment of the DLD-1 and RKO cells with the endomorphin-2 analog increased the expression of Bax and reduced the expression of Bcl-2. CONCLUSIONS Endomorphin-2 analog inhibited colon cancer cell proliferation, activated apoptosis, and down-regulated Akt phosphorylation of human DLD-1 and RKO colon cancer cells in vitro in a dose-dependent manner.

Xanthohumol protects against Azoxymethane-induced colorectal cancer in Sprague-Dawley rats.

Colorectal cancer (CRC) is a major health problem and third most common deaths in western world. Dietary interventions together with modified dietary style can prevent the CRC in humans. Xanthohumol (XHA), a polyphenol isolated from Humulus lupulus L. contains many beneficial effects. The aim of the study is to analyze the effect of XHA on Azoxymethane (AOM)-induced experimental CRC in rats. Levels of MDA were increased and enzymic antioxidants levels were decreased in AOM-induced rats. However, these levels were reversed upon XHA treatment. Further, the mRNA expressions of iNOS and COX-2 were also downregulated in XHA treated rats compared to AOM-induced rats. Further, we found that administration of XHA suppressed the wnt/ß-catenin signaling together with modulation of apoptotic proteins Bax, Bcl-2, and caspase 3. We conclude that XHA can able to quench the free radicals, inhibits cell proliferation and induces apoptosis, thus it can be a chemopreventive/therapeutic agent against CRC.

Forkhead box O3 promotes colon cancer proliferation and drug resistance by activating MDR1 expression.

BACKGROUND: Globally, colon cancer (CC) is the third reason of tumor-related deaths. Previous reports indicate that Forkhead box O3 (FOXO3) is involved in the development of various tumors and may have different effects depending upon the types of tumors. Hence, this study was to examine the effects of FOXO3 on CC cells and uncover the possible mechanisms. METHODS: MTT and cell count assay were applied to analyze the viability of transfected CC cells. rVista, dual luciferase reporter assay, and chromatin immunoprecipitation assay were used to identify the downstream target of FOXO3 in HCT116 cells. The mRNA and protein abundance of FOXO3 and MDR1 were determined by quantitative PCR and Western blot, respectively. RESULTS: Forkhead box O3 stimulated the proliferation of both HCT116 and DLD1 cells. Moreover, FOXO3 overexpression inhibited doxorubicin sensitivity of HCT116 cells, while the knockout of FOXO3 by FOXO3 shRNA restored the doxorubicin sensitivity in doxorubicin-resistant HCT116 DR cells. Next, we found that FOXO3 directly bound to the promoter of MDR1 and enhanced MDR1 expression in HCT116 cells. MDR1 overexpression enhanced the viability and doxorubicin resistance of CC cells. Besides, MDR1 overexpression plasmid significantly abrogated the decrease in cell proliferation and resistance of HCT116 cells to doxorubicin caused by FOXO3 knockout. CONCLUSION: Forkhead box O3 exhibited promotive effects on the proliferation and doxorubicin resistance in CC cells via targeting MDR1.

Irinotecan and 5-fluorouracil-co-loaded, hyaluronic acid-modified layer-by-layer nanoparticles for targeted gastric carcinoma therapy.

For targeted gastric carcinoma therapy, hyaluronic acid (HA)-modified layer-by-layer nanoparticles (NPs) are applied for improving anticancer treatment efficacy and reducing toxicity and side effects. The aim of this study was to develop HA-modified NPs for the co-loading of irinotecan (IRN) and 5-fluorouracil (5-FU). A novel polymer-chitosan (CH)-HA hybrid formulation (HA-CH-IRN/5-FU NPs) consisting of poly(d,l-lactide-co-glycolide) (PLGA) and IRN as the core, CH and 5-FU as a shell on the core and HA as the outmost layer was prepared. Its morphology, average size, zeta potential and drug encapsulation ability were evaluated. Human gastric carcinoma cells (MGC803 cells) and cancer-bearing mice were used for the testing of in vitro cytotoxicity and in vivo antitumor efficiency of NPs. HA-CH-IRN/5-FU NPs displayed enhanced antitumor activity in vitro and in vivo than non-modified NPs, single drug-loaded NPs and drugs solutions. The results demonstrate that HA-CH-IRN/5-FU NPs can achieve impressive antitumor activity and the novel targeted drug delivery system offers a promising strategy for the treatment of gastric cancer.

Maternal Coffee Consumption During Pregnancy and Neural Tube Defects in Offspring: A Meta-Analysis.

PURPOSE: To examine the association between maternal coffee consumption during pregnancy and the occurrence of neural tube defects (NTDs) in offspring. METHODS: PubMed, Springer Link and Elsevier databases were searched up to August, 2014. Case-control and cohort studies published on the association between maternal coffee consumption during pregnancy and the occurrence of NTDs in offspring were included. Meta-analysis was applied to calculate the pooled effect estimates and their 95% confidence intervals (CIs) using a random-effects model. RESULTS: A total of six case-control studies and one cohort study were included. The pooled effect estimate of maternal coffee consumption during pregnancy was 0.86 for total NTDs (95% CI: 0.51- 1.45) and 1.30 (95% CI: 0.67- 2.52) for NTDs subtype of spina bifida. CONCLUSIONS: Our findings suggested that maternal coffee consumption during pregnancy was not significantly associated with the occurrence of total NTD or the spina bifida subtype of NTD.

The Efficacy of Leviteracetam versus Carbamazepine for Epilepsy: A Meta-Analysis.

Leviteracetam (LEV) is a novel antiepileptic drug with improved tolerance and safety, while carbamazepine (CBZ) represents classical antiepileptic drugs. So far, a systemic comparison of the efficacy and side effects of these two drugs is lacking. A literature review on the comparison of leviteracetam versus carbamazepine for patients with epilepsy was performed up to September 2013 using PubMed, EMBASE, the Cochrane Library and ISI web of science. Finally, 3 randomized controlled trials (RCT) studies met the criteria on comparing the efficacy of leviteracetam versus carbamazepine for patients with epilepsy were included for meta-analysis. Stata 11.0 was used to analyze and summarize the respective data. Three RCTs met the entry criteria. The relative risk (RR) and 95% and the confidence interval (CI) of leviteracetam versus carbamazepine for 6- and 12-month seizure free intervals were 1.0 (0.91-1.10) and 0.97 (0.84-1.13), respectively, for therapy discontinuation due to adverse events (AEs) were 0.62 (0.48-0.80) and 1.00 (0.94-2.05), respectively, and for withdrawal after 6- and 12-month treatment were 0.8 (0.64-0.99) and 0.87 (0.74-1.03), respectively. The RR and 95% CI for occurrence of headache, fatigue, diarrhea, vertigo, nasopharyngitis, depression, weight gain and rash were 0.88 (0.73-1.06), 1.08(0.63-1.83), 1.23 (0.66-2.28), 0.92 (0.49-1.71), 0.85 (0.59-1.22), 2.15 (1.26-3.68), 0.69 (0.45-1.04), 0.39 (0.23-0.68), respectively. The major outcomes such as rate of seizure freedom were similar between leviteracetam and carbamazepine. However, leviteracetam led to depression more frequently than carbamazepine, while carbamazepine caused rash more frequently. However, the limited numbers of available RCTs studies and included patients in this study made our results less convincing and accurate.