Effect Of Co-treatment Research Articles

Puerarin and betahistine treatment of vertebrobasilar ischemia vertigo: A meta-analysis of randomized controlled trials.

The present meta-analysis aimed to evaluate the effectiveness and safety of puerarin co-treatment with betahistine in treating vertebrobasilar ischemia (VBI) vertigo. A total of 6 medical databases were searched, identifying randomized controlled trials (RCTs) of VBI vertigo performed until August 2014 that investigated a combined treatment of puerarin with betahistine or with other conventional drugs. The quality of the literature was evaluated using the Cochrane Collaboration's tool for assessing risk of bias, and Rev Man 5.0 software was used for statistical analysis and evaluation. The present study included 7 RCTs, involving a total of 664 subjects, and revealed a statistically significant increase in efficacy between the control and the experimental group (odds ratio [OR], 4.99; 95% confidence interval [CI], 3.05 to 8.15). The average blood flow velocity within the vertebrobasilar arteries increased following treatment with puerarin and betahistine compared with that of the control groups (OR, 7.59; 95% CI, 6.19 to 9.00); however, no difference was detected between these groups in the average flow velocity within the left vertebral artery (OR, 6.17; 95% CI, 5.22 to 7.13). The frequency of adverse reactions in the experimental group was lower (OR, 0.75; 95% CI, 0.32 to 1.77) compared with the control group. Combined puerarin and betahistine regimens were more effective in treating VBI vertigo compared with other, conventional drugs; effectively alleviating the associated symptoms, including dizziness and increased average blood flow velocity within the vertebrobasilar arteries, without causing an increased number of serious side effects. However, the efficacy and safety of puerarin and betahistine use in treating VBI vertigo requires additional investigation.

Metformin Protects H9C2 Cardiomyocytes from High-Glucose and Hypoxia/Reoxygenation Injury via Inhibition of Reactive Oxygen Species Generation and Inflammatory Responses: Role of AMPK and JNK.

Metformin is a first-line drug for the management of type 2 diabetes. Recent studies suggested cardioprotective effects of metformin against ischemia/reperfusion injury. However, it remains elusive whether metformin provides direct protection against hypoxia/reoxygenation (H/R) injury in cardiomyocytes under normal or hyperglycemic conditions. This study in H9C2 rat cardiomyoblasts was designed to determine cell viability under H/R and high-glucose (HG, 33 mM) conditions and the effects of cotreatment with various concentrations of metformin (0, 1, 5, and 10 mM). We further elucidated molecular mechanisms underlying metformin-induced cytoprotection, especially the possible involvement of AMP-activated protein kinase (AMPK) and Jun NH(2)-terminal kinase (JNK). Results indicated that 5 mM metformin improved cell viability, mitochondrial integrity, and respiratory chain activity under HG and/or H/R (P < 0.05). The beneficial effects were associated with reduced levels of reactive oxygen species generation and proinflammatory cytokines (TNF-α, IL-1α, and IL-6) (P < 0.05). Metformin enhanced phosphorylation level of AMPK and suppressed HG + H/R induced JNK activation. Inhibitor of AMPK (compound C) or activator of JNK (anisomycin) abolished the cytoprotective effects of metformin. In conclusion, our study demonstrated for the first time that metformin possessed direct cytoprotective effects against HG and H/R injury in cardiac cells via signaling mechanisms involving activation of AMPK and concomitant inhibition of JNK.

No synergism between bis(propyl)-cognitin and rasagiline on protecting dopaminergic neurons in Parkinson's disease mice.

Rasagiline, a monoamine oxidase-B inhibitor, and bis(propyl)-cognitin (B3C), a novel dimer are reported to be neuroprotective. Herein, the synergistical neuroprotection produced by rasagiline and B3C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice of Parkinsonism. By using neurobehavioural tests, high-performance liquid chromatography and western blot assay, we showed that B3C at 0.3 mg/kg, rasagiline at 0.02 mg/kg, as well as co-treatment with B3C and rasagiline prevented MPTP-induced behavioural abnormities, increased the concentrations of dopamine and its metabolites in the striatum, and up-regulated the expression of tyrosine hydroxylase in the substantia nigra. However, the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3C or rasagiline alone. Collectively, we have demonstrated that B3C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.

Translating G-CSF as an Adjunct Therapy to Stem Cell Transplantation for Stroke.

Among recently investigated stroke therapies, stem cell treatment holds great promise by virtue of their putative ability to replace lost cells, promote endogenous neurogenesis,and produce behavioral and functional improvement through their "bystander effects." Translating stem cell in the clinic, however, presents a number of technical difficulties. A strategy suggested to enhance therapeutic utility of stem cells is combination therapy, i.e., co-transplantation of stem cells or adjunct treatment with pharmacological agents and substrates,which is assumed to produce more profound therapeutic benefits by circumventing limitations of individual treatments and facilitating complementary brain repair processes. We previously demonstrated enhanced functional effects of cotreatment with granulocyte-colony stimulating factor (GCSF)and human umbilical cord blood cell (hUCB) transplantation in animal models of traumatic brain injury (TBI). Here,we suggest that the aforementioned combination therapy may also produce synergistic effects in stroke. Accordingly, G-CSF treatment may reduce expression of pro-inflammatory cytokines and enhance neurogenesis rendering a receptive microenvironment for hUCB engraftment. Adjunct treatment of GCSF with hUCB may facilitate stemness maintenance and guide neural lineage commitment of hUCB cells. Moreover, regenerative mechanisms afforded by G-CSF-mobilized endogenous stem cells, secretion of growth factors by hUCB grafts and G-CSF-recruited endothelial progenitor cells(EPCs), as well as the potential graft–host integration that may promote synaptic circuitry re-establishment could altogether produce more pronounced functional improvement in stroked rats subjected to a combination G-CSF treatment and hUCB transplantation. Nevertheless, differences in pathology and repair processes underlying TBI and stroke deserve consideration when testing the effects of combinatorial G-CSF and hUCB cell transplantation for stroke treatment. Further studies are also required to determine the safety and efficacy of this intervention in both preclinical and clinical stroke studies.

Thrombin inhibition and cyclophosphamide synergistically block tumor progression and metastasis

Cancer is often associated with an increased risk of thrombotic events which are exacerbated by treatment with chemotherapeutics such as cyclosphosphamide (CP). Evidence suggests that thrombin can stimulate tumor progression via formation of fibrin and activation of protease-activated receptors (PARs) and platelets. We examined the effect of co-treatment with CP and dabigatran etexilate, a direct inhibitor of thrombin, using the murine orthotopic 4T1 tumor model. Mice receiving co-treatment with both low dose CP and dabigatran etexilate had significantly smaller mammary tumors and fewer lung metastases than mice treated with CP or dabigratran etexilate alone. Co-treatment with dabigatran etexilate and low dose CP also significantly decreased the number of arginase+Gr-1+CD11b+ myeloid derived suppressor cells as well as levels of TGF-β in spleens from tumor bearing mice. 4T1 tumors express procoagulant tissue factor (TF) and spontaneously release TF+ microparticles which are potent procoagulant factors that promote thrombin generation. Treatment with dabigatran etexilate alone prevented tumor-induced increases in circulating TF+ microparticles and also decreased the numbers of tumor-induced activated platelets by 40%. These results show that co-treatment with dabigatran etexilate and CP synergistically inhibits growth and metastasis of mammary tumors, suggesting that oral administration of the thrombin inhibitor dabigatran etexilate may be beneficial in not only preventing thrombotic events in cancer patients but also in treating malignant tumors themselves.

Retino-protective effect of Bucida buceras against oxidative stress induced by H2O2 in human retinal pigment epithelial cells line.

BackgroundReactive Oxygen Species (ROS) impair the physiological functions of Retinal Pigment Epithelial (RPE) cells, which are known as one major cause of age-related macular degeneration and retinopathy diseases. The purpose of this study is to explore the cytoprotective effects of the antioxidant Bucida buceras extract in co-treatment with hydrogen peroxide (H2O2) delivery as a single addition or with continuous generation using glucose oxidase (GOx) in ARPE-19 cell cultures. The mechanism of Bucida buceras extract is believed to be associated with their antioxidant capacity to protect cells against oxidative stress.MethodsA comparative oxidative stress H2O2-induced was performed by addition and enzymatic generation using glucose oxidase on human retinal pigment epithelial cells line. H2O2-induced injury was measured by toxic effects (cell death and apoptotic pathway) and intracellular redox status: glutathione (GSH), antioxidant enzymes (catalase and glutathione peroxidase) and reducing power (FRAP). The retino-protective effect of co-treatment with Bucida buceras extract on H2O2-induced human RPE cell injury was investigated by cell death (MTT assay) and oxidative stress biomarkers (H2O2, GSH, CAT, GPx and FRAP).ResultsBucida buceras L. extract is believed to be associated with the ability to prevent cellular oxidative stress. When added as a pulse, H2O2 is rapidly depleted and the cytotoxicity analyses show that cells can tolerate short exposure to high peroxide doses delivered as a pulse but are susceptible to lower chronic doses. Co-treatment with Bucida buceras was able to protect the cells against H2O2-induced injury. In addition to preventing cell death treatment with antioxidant plant could also reverse the significant decrease in GSH level, catalase activity and reducing power caused by H2O2.ConclusionThese findings suggest that Bucida buceras could protect RPE against ocular pathogenesis associated with oxidative stress induced by H2O2-delivered by addition and enzymatic generation.

Mangiferin Protects Retinal Ganglion Cells in Ischemic Mouse Retina via SIRT1

Purpose: To investigate whether mangiferin can increase the viability of retinal ganglion cells (RGCs) in ischemic mouse retina, and to determine the possible mechanism of neuroprotection.Methods: C57BL/6J mice underwent constant elevation of intraocular pressure for 60 min and received saline or mangiferin (30 mg/kg) intraperitoneally once daily until sacrifice. HIF-1α, GFAP and SIRT1 expression was assessed at 1, 4, and 7 days after retinal ischemia. Bax and Bcl-2 expression was also analyzed at 1 and 4 days. RGC survival was assessed by labeling flat-mounted retinas with Brn3a at 2 weeks after retinal ischemia. The effect of co-treatment with mangiferin and sirtinol (SIRT1 inhibitor) was also evaluated.Results: The expression of HIF-1α and GFAP was upregulated in saline-treated retinas within 7 days after ischemia. Mangiferin treatment suppressed this upregulation. The expression of SIRT1 was downregulated in saline-treated ischemic retinas. This downregulation was reversed by mangiferin treatment, resulting in a significant difference from saline-treated ischemic retinas. In mangiferin-treated ischemic retinas, Bax expression was downregulated, whereas Bcl-2 expression was upregulated in comparison with saline-treated ischemic retinas. Mangiferin treatment protected ischemic retinas against RGC loss. Treatment of sirtinol decreased the neuroprotective effect of mangiferin.Conclusions: Our findings suggest that mangiferin has a neuroprotective effect on RGC through downregulation of HIF-1a and GFAP, and upregulation of SIRT1 in ischemic mouse retinas. We suggest that mangiferin might be a potential neuroprotective agent against RGC loss under oxidative stress.

Effects of red mold dioscorea with pioglitazone, a potentially functional food, in the treatment of diabetes

The prevalence of type 2 diabetes mellitus is increasing rapidly, and its treatment with pioglitazone is likely to induce rhabdomyolysis. We aimed to determine the effect of cotreatment with pioglitazone and red mold dioscorea (RMD) produced by Monascus purpureus NTU 568 on pancreas function in streptozotocin (STZ)-induced diabetic rats. In diabetic rats fed RMD, RMD with pioglitazone, and pioglitazone alone, insulin concentrations increased significantly by 18.6–40.4%, 64.0–100.0%, and 52.8%, respectively, compared with that in the diabetic group (p < 0.05). Oral glucose tolerance was impaired in the STZ-induced diabetic group within 4 weeks, however, oral glucose tolerance in rats treated with RMD or RMD with pioglitazone improved after 4 weeks, 6 weeks, and 8 weeks. Findings from this study might lend support to the use of RMD as a novel functional food for the prevention of diabetes.

Behavioral impairments and serotonin reductions in rats after chronic L-dopa

L-dopa, the main therapeutic for Parkinson's disease (PD), has been shown to increase brain dopamine concentrations that are necessary for proper motor control; however, PD patients experience non-motor symptoms that are not improved or could be exacerbated by L-dopa. The purpose of this study is to determine the effects of L-dopa treatment on cognitive and affective behavioral responses of rats, as well as their corresponding monoamine brain concentrations. Rats were treated with L-dopa (6 mg/kg; twice daily) for 10 consecutive days. Sodium ascorbate (400 mg/kg) was co-administered with L-dopa to investigate the effects of antioxidant co-treatment on behavior and monoamine concentrations. Rats underwent cognitive and affective behavioral testing. Monoamine concentrations of several brain regions were analyzed. L-dopa treatment resulted in significant impairment in the performance in the Barnes maze and improvement in conditioned fear stress paradigms. Specifically, L-dopa caused an increase in latency to find the goal box during Barnes maze testing and increased freezing behavior in context-induced conditioned fear testing. Furthermore, the rats in the conditioned fear stress experiments showed corresponding depletions in serotonin (5-HT) and its metabolite, 5-HIAA, in the dorsal raphe nucleus (DRN) and the mPFC. The behavioral impairments as well as monoamine depletions were blocked by ascorbate co-treatment. Chronic L-dopa may contribute to non-motor symptoms related to spatial memory and fear. These effects may be attributable to a dysregulation of brain 5-HT caused by L-dopa treatment. The results presented here provide further rationale for investigating adjunctive therapeutics to L-dopa for PD, such as antioxidants.

PTH-272 Modulation of NRF2 alters the responsiveness of colorectal cancer cells to irinotecan

<h3>Introduction</h3> Chemotherapy is essential to improve outcomes in colorectal cancer (CRC). Irinotecan is a pro-drug commonly used in CRC which requires conversion to the active metabolite Sn38. The cytoprotective protein NRF2 has been associated with chemo-resistance and a worse prognosis in a number of cancers.¹It also regulates the activity of enzymes (including CES1 and UGT1A1) that coordinate irinotecan metabolism and efflux. ²NRF2 remains bound to the regulatory protein KEAP1 in its quiescent state. The aim of this study is to establish the value of modulating NRF2 as a novel strategy for enhancing the efficacy of irinotecan-based chemotherapy either through increased conversion of irinotecan to Sn38 or by sensitisation of CRC cells to its effect. <h3>Method</h3> NRF2 was modulated in the human CRC cell line HCT116 using small inhibitory RNA (siRNA) targeting <i>NRF2</i>and <i>KEAP1 </i>or the chemical inhibitor brusatol and inducer CDDO-Me. Cells were then exposed to irinotecan over a range of concentrations for 48 h. Cell viability was measured by MTS assay and expressed as a percentage of control for the calculation of IC₅₀values. GraphPad Prism 6^®was used for all statistical analysis and the generation of dose-response curves. <h3>Results</h3> Successful NRF2 modulation was confirmed by western blotting for Nrf2 and downstream targets NQO1 and HO-1. The IC₅₀value of irinotecan in untreated control cells was 90µM. Induction of NRF2 by <i>KEAP1</i>siRNA (IC₅₀220µM) or CDDO-Me (IC₅₀325µM) significantly reduced irinotecan cytotoxicity (p &lt; 0.0001). In contrast, inhibition of NRF2 by <i>NRF2</i>siRNA (IC₅₀11µM) or brusatol (IC₅₀55µM) had the opposite effect (p &lt; 0.0001). <h3>Conclusion</h3> Inhibition of NRF2 sensitises CRC cells to irinotecan cytotoxicity and may allow improved response to treatment, or permit lower doses with fewer side effects. We are currently validating these findings <i><i>in vivo</i></i>and examining the contribution of processes that mediate the disposition of irinotecan. The availability of NRF2 inhibiting and inducing compounds may allow for successful modulation in the clinical setting. <h3>Disclosure of interest</h3> J. Evans Grant/ Research Support from: Cancer Research UK, B. Winiarski: None Declared, P. Sutton: None Declared, D. Palmer: None Declared, N. Kitteringham: None Declared. <h3>References</h3> Kawasaki Y, Ishigami S, Arigami T, Uenosono Y, Yanagita S, Uchikado Y, <i>et al</i>. Clinicopathological significance of nuclear factor (erythroid-2)-related factor 2 (Nrf2) expression in gastric cancer. BMC Cancer 2015;<b>15</b>(1):5 Wang M, Zhu JY, Chen S, Qing Y, Wu D, Lin YM, <i>et al</i>. Effects of co-treatment with sulforaphane and autophagy modulators on uridine 5’-diphospho-glucuronosyltransferase 1A isoforms and cytochrome P450 3A4 expression in Caco-2 human colon cancer cells. Oncol Lett. 2014;8(6):2407–16

Registered report: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs.

The Science in 2010 (Sugahara et al., 2010). The key experiments being replicated include Figure 2 and Supplemental Figure 9A. In Figure 2, Sugahara and colleagues presented data on the tumor penetrance of doxorubicin (DOX) when co-administered with the peptide iRGD, as well as the effect of co-treatment of DOX and iRGD on tumor weight and cell death. In Supplemental Figure 9A, they tracked body weight of mice treated with DOX and iRGD to provide evidence that iRGD does not increase known DOX toxicity. The Reproducibility Project: Cancer Biology is a collaboration between the eLife.

The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles.

Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24 h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6 mg/kg) and four days later, they were exposed intratracheally to DEP (0.5 mg/kg), and were sacrificed 24 h later. Oral TQ (20 mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP.

Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections.

Clindamycin, a lincosamide antibiotic with a good penetration into bone, is widely used for treating bone and joint infections by Gram-positive pathogens. To be active against Staphylococcus spp, its concentration at the infection site, C, must be higher than 2× the minimal inhibitory concentration (MIC). The aims of the work were to study the determinants of plasma clindamycin trough concentration, C min, especially the effect of co-treatment with rifampicin, and the consequences on clinical outcome. An observational study was performed, involving patients hospitalized for a bone and joint infection who received clindamycin as part of their antibiotic treatment. Target C min was 1.7 mg/L, to reach the desired bone concentration/MIC >2, assuming a 30% diffusion into bone and MIC = 2.5 mg/L. Sixty one patients (mean age: 56.8 years, 57.4% male) were included between 2007 and 2011. 72.1% underwent a surgery on a foreign material, and 91.1% were infected by at least a Gram-positive micro-organism. Median C min value was 1.39 mg/L, with 58% of the values below the threshold value of 1.7 mg/L. Median C min was significantly lower for patients taking rifampicin (0.46 vs 1.52 mg/L, p = 0.034). No patient with rifampicin co-administration reached the target concentration (maximal C min: 0.85 mg/L). After a median follow-up of 17 months (1.5-38 months), 4 patients relapsed, 2 died and 47 (88.7% of the patients with known outcome) were cured, independently of association with rifampicin. This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.

Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.

BackgroundHeroin use among young women of reproductive age has drawn much attention around the world. Although methadone is widely used in maintenance therapy for heroin/morphine addiction, the long-term effects of prenatal exposure to methadone and preventative therapy remain unclear. For revealing this question, female pregnant Sprague–Dawley rats were sub-grouped to receive (1) vehicle, (2) methadone 5 mg/kg at embryonic day 3 (E3) and then 7 mg/kg from E4 to E20, (3) dextromethorphan (DM) 3 mg/kg, and (4) methadone + DM (the rats received methadone followed by DM treatment), subcutaneously, twice a day from E3 to E20. The body weight, natural withdrawal, pain sensitivity, ED50, conditioned place preference and water maze were conducted at different postnatal stages (P1 to P79) of offspring. The quantitative real-time RT-PCR and electrophysiology were also used to measure the gene expression of opioid receptors in the spinal cord and changes of LTP/LTD in the hippocampus, separately.ResultsPrenatal exposure to methadone or DM did not affect survival rate, body weight, water maze and LTP or LTD of offspring. However, prenatal methadone significantly increased the withdrawal symptoms, pain sensitivity, addiction liability and decreased the mRNA expression of pain related opioid receptors. Co-administration of DM with methadone in the maternal rats effectively prevented these abnormalities of offspring induced by methadone.ConclusionsOur study clearly showed that co-administration of dextromethorphan with methadone in the maternal rats prevented the adverse effects induced by prenatal methadone exposure. It implies that dextromethorphan may have a potential to be used in combination with methadone for maintenance treatment in pregnant heroin-addicted women to prevent the adverse effects induced by methadone on offspring.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-015-0126-2) contains supplementary material, which is available to authorized users.

Single versus simultaneous species treatment of wood with Ceriporiopsis subvermispora and Postia placenta for ethanol applications, with observations on interspecific growth inhibition

In order to examine the potential efficacy of simultaneous dual-species fungal treatment of wood for lignocellulosic ethanol production, whole organism fungal biopulping methods utilizing white rot (Ceriporiopsis subvermispora) and brown rot (Postia placenta) fungi alone or in co-culture were compared for effect on wood microstructure, chemical composition, and enzymatic sugar solubilization. Liriodendron tulipifera wood chips exposed for 30 days to C. subvermispora and/or P. placenta fungi alone or in co-culture exhibited qualitative differences in wood microstructure, but did not significantly differ in final percent composition of holocellulose, α-cellulose, or lignin content compared to controls. All fungal treatments increased the soluble reducing sugar yield of enzymatic hydrolysis by ca. 28–30% over sterile controls. The co-culture fungal treatment did not significantly differ in reducing sugar yield compared to monoculture treatments, suggesting an unexpected lack of additive or other synergistic species effects on wood degradation using these fungi in co-culture. Paired interaction agar plate assays demonstrated that C. subvermispora and P. placenta exhibited mutual distance-mediated growth inhibition that was independent of substrate type or availability, suggesting an explanation for the observed lack of degradative synergy between these taxa. This study is the first to report the effects of simultaneous co-treatment with white and brown rot fungi, highlights the need for further optimization of methods to account for specialized fungal degradative mechanisms, and examines the potential influence of competitive interactions in whole-organism biopulping treatments utilizing different taxa.

Effects of co-treatment of &lt;i&gt;Rauwolfia vomitoria&lt;/i&gt; and &lt;i&gt;Gongronema latifolium&lt;/i&gt; on neurobehaviour and the neurohistology of the cerebral cortex in mice

Rauwolfia vomitoria and Gongronema latifolium are medicinal plants with antioxidant, antidiabetic and analgesic properties among others. R. vomitoria is reported to possess adverse neural effects, which G. latifolium has shown the potential to address. This study therefore investigated the effects of co-treatment of R. vomitoria and G. latifolium on the neurobehaviour and histology of the cerebral cortex of female mice. Twenty female Wistar mice were divided into 4 groups (A, B, C and D). Group A designated as the control received 0.4 mL of 20 % Tween, while groups B, C and D received oral doses of 150 mg/kg of R. vomitoria (RV), 200 mg/kg of G. latifolium (GL) and a combination of 150 mg/kg of R. vomitoria and 200 mg/kg of G. latifolium (RV+GL), respectively for seven days. Light and dark field behaviour test was carried out on day 8 and the animals were immediately sacrificed. Their brains were excised and routinely processed by haematoxylin and eosin method. There was no difference in body and brain weights, and the behavioural parameters. Cellular cyto-architecture showed higher glial population with no apparent histopathology. The cellular population was higher (p&lt;0.0001) in the RV and RV+GL groups, while the GL group was less (p&lt;0.0001) populated all compared to the control.In conclusion, the reported treatment regimes, RV administered singly and in combination with GL may not affect some neurobehavioural activities, but may result in cellular increase in the cerebral cortex.KEY WORDS: Rauwolfia vomitoria; Gongronema latifolium; Cerebral cortex; Mice

Effect of co-administration of Angelicae gigantis radix and Lithospermi radix on rat hepatic injury induced by carbon tetrachloride.

Background:Co-administration of Angelicae gigantis radix (AGR) and Lithospermi radix (LR) has been commonly applied to patients to treat cardiac and hepatic disorders. Individual bioactivities of these herbal medicines have been widely investigated, but the hepatoprotective effects of co-treatment of AGR and LR have yet to be clarified.Objective:The present study investigated the protective effects of extracts of AGR and LR on carbon tetrachloride (CCl4) induced hepatic injury.Materials and Methods:In this study, we measured the hepatoprotective activity of individual and co-treatment of the two herbal medicines on hepatic injury induced by CCl4 by measuring different biochemical parameters such as serum aspartate aminotransaminase (AST) and serum alanine aminotransaminase (ALT). Microarray technology also used to compare ontological difference with individual and co-treatment of these two.Results:Combined treatment with AGR and LR (AGR + LR) decreased AST and ALT level in serum which demonstrate hepatoprotective effect of the therapy. When the effect of AGR and LR according to treatment conditions was measured, co-treatment showed the most prominent effect on hepatic injury by CCl4 rather than individual treatment condition. We further defined gene set that could be the molecular target of herbal effect on hepatic injury by CCl4 using bioinformatical analysis of interaction network. Highly recovered genes by treating AGR + LR play significant roles in response to hepatic injury induced by CCl4.Conclusion:Combined treatment with AGR and LR showed synergistic protective effects on the CCl4-induced rat hepatic tissue injury.

Cooperative effects of hydrogen sulfide and nitric oxide on delaying softening and decay of strawberry

Abstract: Hydrogen sulfide (H2S) and nitric oxide (NO) as two signal molecules play prominent roles in plant response to biotic stress. The combination effects of these two molecules on ripening and decay of postharvest strawberry were investigated. Strawberries were first dipped in distilled water, 0.8 mmol/L NaHS solution, 5 µmmol/L sodium nitroprusside (SNP) solution, and combinative solutions of 0.8 mmol/L NaHS and 5 µmmol/L SNP for 10 min, respectively, and then stored at 20°C. Results showed that the effects of the co-treatment of 0.8 mmol/L NaHS solution and 5 µmmol/L SNP solution were superior to that of other treatments. The former could suppress the percentage of fruit decay, inhibit respiration rate, maintain the original crust color, and slow down the decrease of firmness and the change of relative conductivity, which preserved the fruit quality. Further investigation showed that co-treatment of hydrogen sulfide and nitric oxide maintained higher activities of chitinase (CHI) and beta-1,3-glucanase (GNS), and lowered activities of pectin methylesterase (PME), polygalacturonase (PG) and endo-β-1,4-glucanase (EGase). The study indicated that the synergistic function of H2S and NO could effectively prolong the shelf life and reduce the decay rate of harvested strawberry. Keywords: hydrogen sulfide, nitric oxide, strawberry, enzyme activities, shelf life DOI: 10.3965/j.ijabe.20140706.014 Citation: Zhang C, Shi J Y, Zhu L P, Li C L, Wang Q G. Cooperative effects of hydrogen sulfide and nitric oxide on delaying softening and decay of strawberry. Int J Agric & Biol Eng, 2014; 7(6): 114－122

Live birth rates after combined adjuvant therapy in IVF–ICSI cycles: a matched case-control study

The effectiveness of combined co-treatment with aspirin, doxycycline, prednisolone, with or without oestradiol patches, was investigated on live birth (LBR) rates after fresh and frozen embryo transfers (FET) in IVF and intracytoplasmic sperm injection cycles. Cases (n = 485) and controls (n = 485) were extensively matched in a one-to-one ratio on nine physical and clinical parameters: maternal age, body mass index, smoking status, stimulation cycle number, cumulative dose of FSH, stimulation protocol, insemination method, day of embryo transfer and number of embryos transferred. No significant differences were found in fresh cycles between cases and controls for the pregnancy outcomes analysed, but fewer surplus embryos were available for freezing in the combined adjuvant group. In FET cycles, LBR was lower in the treatment group (OR: 0.49, 95% CI 0.25 to 0.95). The lower LBR in FET cycles seemed to be clustered in patients receiving combined adjuvant treatment without luteal oestradiol (OR 0.37, 95% CI 0.17 to 0.80). No difference was found in LBR between cases and controls when stratified according to the number of previous cycles (<3 or ≥3). There is no benefit of this combined adjuvant strategy in fresh IVF cycles, and possible harm when used in frozen cycles.

214 TRICLOSAN-INDUCED CELL CYCLE RELATED AND APOPTOTIC RELATED GENES WERE REVERSED BY KAEMPFEROL IN IN VITRO BREAST CANCER AND XENOGRATED MOUSE MODELS

Triclosan (Tri) is one of many endocrine-disrupting chemicals (EDCs) that are scattered with environment agents, such as toothpastes, deodorants, and cleaning supplies. As a phytoestrogen, kaempferol (Kae) is one of bioflavonoids, which has been found in a variety of vegetables including broccoli, tea, and tomatoes. Although Kae may have anti-cancer activity, its exact mechanism is under investigation, and might be the induction of apoptosis and inhibition of cell proliferation or angiogenesis. In this study, we examined the anti-proliferative effects of Kae in Tri-induced cell growth in MCF-7 breast cancer cells. A proper concentration and co-treatment effect of Tri and Kae were determined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay to measure cell viability in vitro. MCF-7 cells were cultured with a negative control (0.1% DMSO), E2 (1 × 10–9 M), Tri (10–5–10–8 M) and Kae (50, 70, and 90 mM). In this study, treatment with Tri (10–6 M) increased the cell viability of MCF-7 cells, while Kae (50 mM) significantly reduced the cell viability compared to the negative control (P &lt; 0.05). In addition, Kae significantly reversed Tri-induced MCF-7 cell growth at 50 mM compared with a higher concentration (100 mM; P &lt; 0.05). To confirm that Kae inhibited Tri-induced cell growth, we examined the transcriptional levels of cell growth and apoptosis-related markers, i.e. cyclin D, p21, cyclin E, p27 and bcl-2, and bax genes, using reverse transcription (RT)-PCR. The expression levels of cyclin D, cyclin E, and bax/bcl-2 ratio were increased, while those of p21 and p27 mRNAs were decreased by Tri in MCF-7 cells. In addition, Kae treatment significantly reversed Tri-induced gene expressions in an opposite manner. In parallel with its mRNA level, the protein level of cyclin E, p-ERK and p-MEK1/2 were induced by Tri while it was reversed by Kae as shown by Western blot analysis. The expression levels of p21 and bax genes were altered by Tri and reversed by Kae treatment in this study. As an in vivo model, a xenografted mouse model was generated following injection with MCF-7 breast cancer cells in 6 weeks. In parallel with in vitro results, tumour volumes following treatment with E2 and Tri were continually increased compared to a vehicle (corn oil). It was of interest that treatment of the mice with combination of E2 plus Kae or Tri plus Kae showed less tumour formation rather than that of singly treated mice with E2 or Tri. Taken together, these results indicate that Kae may inhibit the growth of MCF-7 cells via regulating of cell cycle and apoptosis-related genes. In addition, EDC-induced progression of breast cancer may be suppressed by a phytoestrogen, i.e. Kae, in a specific manner.