Review of recently reported Ricin detection techniques focusing on combined immunoassay detection with abrin and saxitoxin in human plasma

Increasing non-traditional threats from biological or chemical weapons, the Organisation for the Prohibition of Chemical Weapons (OPCW) have tried to perform the preliminary analysis of biotoxin sample to standardize analysis methods and strengthen analytical capabilities among OPCW member countries. With the changes of new analysis, ROK CBRN Defense Research Institute (CDRI) established enzyme-linked immunosorbent assay (ELISA) and cytotoxicity analysis methods for ricin, abrin, and saxitoxin through the OPCW exercise on Biotoxin sample analysis. Thus, this study aims to established analytical methods (ELISA and cytotoxicity analysis) for the biological toxins called ricin, abrin and saxitoxin according to recent OPCW Biotoxin detection exercise. In particular, to refine practical and effective methods of biological analysis, we reviewed recent research on scientific analysis of ricin as a potential bioterror weapon, letter with ricin sent in White House, and suggested future agendas for preparedness testing

The Effects of Gymnema sylvestre in High-Fat Diet-Induced Metabolic Disorders

This study used an integrated approach to investigate the effects of Gymnema sylvestre (GS) extract as a functional dietary supplement with a high-fat diet. This approach examined insulin resistance, the dysfunction of adipose tissue, and liver steatosis. Male C57BL/6J mice were fed a normal chow or high-fat diet (HFD) for the acute and chronic study, in addition to GS in different doses (100, 250 and 500 mg/kg body weight). Their body composition changes, serum lipid and glucose parameters, adipose and liver tissue histology, and gene expression were measured. It was found that GS significantly suppressed the increase of body weight, serum levels of lipid, insulin and leptin, and adipose tissue, and liver inflammation. GS also demonstrated hypoglycemic effects due to the amylase inhibition activity. Our results support the existence of a relationship between the HFD induced insulin resistance, adipose dysfunction and liver steatosis. In conclusion, GS works as a functional dietary supplement with preventative effects against metabolic disorder.

Restoration of mutant K-Ras repressed miR-199b inhibits K-Ras mutant non-small cell lung cancer progression

Background: miRNAs play crucial role in the progression of K-Ras-mutated nonsmall cell lung cancer (NSCLC). However, most studies have focused on miRNAs that target K-Ras. Here, we investigated miRNAs regulated by mutant K-Ras and their functions. Methods: miRNAs regulated by mutant K-Ras were screened using miRNA arrays. miR-199b expression levels were measured by qRT-PCR. The protein expression levels were measured using Western blot and immunohistochemistry. The effects of miR-199b on NSCLC were examined both in vitro and in vivo by overexpressing or inhibiting miR-199b. DNA methylation was measured by bisulfite sequencing. Results: An inverse correlation was observed between K-Ras mutation status and miR-199b levels in NSCLC specimens and cell lines. The inhibition of miR-199b stimulated NSCLC growth and metastasis, while restoration of miR-199b suppressed K-Ras mutation-driven lung tumorigenesis as well as K-Ras-mutated NSCLC growth and metastasis. miR-199b inactivated ERK and Akt pathways by targeting K-Ras, KSR2, PIK3R1, Akt1, and Rheb1. Furthermore, we determined that mutant K-Ras inhibits miR-199b expression by increasing miR-199b promoter methylation. Conclusion: Our findings suggest that mutant K-Ras plays an oncogenic role through downregulating miR-199b in NSCLC and that overexpression of miR-199b is a novel strategy for the treatment of K-Ras-mutated NSCLC.This work was supported by the National Natural Science Foundation of China (81672283 to H.J.) and the Startup Fund for Talented Scholars of Daping Hospital and Research Institute of Surgery, Third Military Medical University (to H.J. and C.-X.X).

Towards a strategic approaches in alternative tests for pesticide safety

Pesticides have provided significant benefits including plant disease control and increased crop yields since people developed and utilized them. However, pesticide use is associated with many adverse effects, which necessitate precise toxicological tests and risk assessment. Most of these methods are based on animal studies, but considerations of animal welfare and ethics require the development of alternative methods for the evaluation of pesticide toxicity. Although the usage of laboratory animals is inevitable in scientific evaluation and alternative approaches have limitations in the whole coverage, continuous effort is necessary to minimize animal use and to develop reliable alternative tests for pesticide evaluation. This review discusses alternative approaches for pesticide toxicity tests and hazard evaluation that have been used in peer-reviewed reports and could be applied in future studies based on the critical animal research principles of reduction, replacement, and refinement

Review of recently reported Ricin detection techniques focusing on combined immunoassay detection with abrin and saxitoxin in human plasma

Increasing non-traditional threats from biological or chemical weapons, the Organisation for the Prohibition of Chemical Weapons (OPCW) have tried to perform the preliminary analysis of biotoxin sample to standardize analysis methods and strengthen analytical capabilities among OPCW member countries. With the changes of new analysis, ROK CBRN Defense Research Institute (CDRI) established enzyme-linked immunosorbent assay (ELISA) and cytotoxicity analysis methods for ricin, abrin, and saxitoxin through the OPCW exercise on Biotoxin sample analysis. Thus, this study aims to established analytical methods (ELISA and cytotoxicity analysis) for the biological toxins called ricin, abrin and saxitoxin according to recent OPCW Biotoxin detection exercise. In particular, to refine practical and effective methods of biological analysis, we reviewed recent research on scientific analysis of ricin as a potential bioterror weapon, letter with ricin sent in White House, and suggested future agendas for preparedness testing

Benomyl-induced effects of ORMDL3 overexpression via oxidative stress in human bronchial epithelial cells

The respiratory system is a major site of exposure route during pesticide use. Although pesticide exposure is associated with chronic respiratory diseases including asthma, the underlying pathophysiological mechanism remains to be elucidated. In this study, we investigated the in vitro effects of benomyl-induced ORMDL3 overexpression on the toxicological mechanism using the human bronchial epithelial cell line 16HBE14o-. Benomyl increased reactive oxygen species and Ca2+ levels, and asthma related ADAM33 and ORMDL3 expression in 16HBE14o- cells. Considering the change in Ca2+ level and protein expression, we focused on ORMDL3 to elucidate the mechanism of benomyl-induced asthma. Antioxidant treatment showed that benomyl-induced ORMDL3 and endoplasmic reticulum stress could be triggered by oxidative stress. Furthermore, ORMDL3 knockdown alleviated the effects of benomyl on intracellular Ca2+, and the expression of metalloproteinases, and proinflammatory cytokines involved in the pathogenesis of asthma. In conclusion, our results suggest that benomyl-induced ORMDL3 over expression via oxidative stress might be a mechanism involved in asthma. Moreover, antioxidants and alleviating mechanisms that reduce ORMDL3 levels could serve as promising therapeutic targets for pesticide-induced asthma. (C) 2016 Elsevier Ltd. All rights reserved

Ultra-Stable Titanium Carbide MXene Functionalized with Heterocyclic Aromatic Amines

2D transition metal carbides (MXenes) obtained from bulk M(n+1)AX(n) (n = 1, 2, 3, or 4) phases are an intriguing class of crystalline solids with unique physicochemical properties for promising applications such as batteries, capacitive energy storage, and electrocatalysis. One of the obstacles that must be overcome for technical applications is that MXene flakes delaminated in aqueous conditions suffer from phase transition and/or structural decomposition over time. Herein, a simple but powerful strategy to enhance their stability by passivating vulnerable edges on the delaminated MXene (Ti3C2Tx) with heterocyclic aromatic amines is reported. In particular, pyrrole-functionalized MXenes are found to facilitate anti-oxidation in aqueous solutions at room temperature over 700 days, at 70 degrees C over 42 days, and even with a strong oxidizer (H2O2, 9.70 mmol) over 50 days. On the other hand, the as-prepared MXene solution lost its color within a month at room temperature, a day at 70 degrees C, and 5 min in the presence of H2O2 (9.70 mmol). Density functional theory calculations indicate that chemical interactions between MXene and pyrrole are extremely strong and involve the formation of Ti-C bonds. Furthermore, pyrrole-functionalized MXenes exhibit higher electrochemical performance than pristine MXenes as a supercapacitor.11Nsciescopu

Chlorpyrifos induces NLRP3 inflammasome and pyroptosis/apoptosis via mitochondrial oxidative stress in human keratinocyte HaCaT cells

Chlorpyrifos (CPF) has been widely used around the world as a pesticide for both agricultural and residential application. Although various studies have reported toxicity and health-related effects from CPF exposure, the molecular mechanism of CPF toxicity to skin has not been well-characterized. The present study determined the potential mechanism involved in skin toxicity of CPF using the HaCaT human skin keratinocyte cell line. After treating to HaCaT cells, CPF triggered reactive oxygen species (ROS) generation and mitochondrial oxidative stress. We focused on NLRP3 inflammasome, known to induce innate immune response. We used mitochondrial ROS (mROS) scavenger mitoTEMPO to demonstrate a role for mROS in NLRP3 inflammasome and programmed cell death induced by CPF. Our results showed that CPF provoked NLRP3 inflammasome and pyroptosis/apoptosis via an increase of mROS in HaCaT cells. This study proposes that CPF induces innate immune response and skin inflammation through activating the NLRP3 inflammasome in skin epithelial cells. CPF may lead to cutaneous disease conditions and antioxidants could be proposed for therapy against skin exposure to CPF. (c) 2015 Elsevier Ireland Ltd. All rights reserved

Ephedrine-induced mitophagy via oxidative stress in human hepatic stellate cells

The herb Ephedra sinica (also known as Chinese ephedra or Ma Huang), used in traditional Chinese medicine, contains alkaloids identical to ephedrine and pseudoephedrine as its principal active constituents. Recent studies have reported that ephedrine has various side effects in the cardiovascular and nervous systems. In addition, herbal Ephedra, a plant containing many pharmacologically active alkaloids, principally ephedrine, has been reported to cause acute hepatitis. Many studies reported clinical cases, however, the cellular mechanism of liver toxicity by ephedrine remains unknown. In this study, we investigated hepatotoxicity and key regulation of mitophagy in ephedrine-treated LX-2 cells. Ephedrine triggered mitochondrial oxidative stress and depolarization. Mitochondrial swelling and autolyso-some were observed in ephedrine-treated cells. Ephedrine also inhibited mitochondrial biogenesis, and the mitochondrial copy number was decreased. Parkin siRNA recovered the ephedrine-induced mitochondrial damage. Excessive mitophagy lead to cell death through imbalance of autophagic flux. Moreover, antioxidants and reducing Parkin level could serve as therapeutic targets for ephedrine-induced hepatotoxicity

Aerosol delivery of folate-decorated hyperbranched polyspermine complexes to suppress lung tumorigenesis via Akt signaling pathway

Lung cancer has been a leading cause of cancer mortality worldwide and aerosol-mediated gene therapy endows numerous advantages compared to other traditional modalities. Here, we reported a folic acid (FA)-modified hyperbranched polyspermine (HPSPE) with prominent biocompatibility for lung cancer cell targeted gene therapy. FA was decorated to the HPSPE via an amidation reaction and the physicochemical properties of nanoplexes formed with DNA were characterized. Gel electrophoresis study elucidated that the designed polymer was capable to condense DNA and protect it from degradation by DNase I. Cell viability and transfection efficiency assay in vitro and in vivo indicated its increased transfection performance with lower toxicity. Furthermore, reduced tumor numbers and down-regulation of Akt1 protein after aerosol treatment containing FA-HPSPE/shAkt1 complexes proved its therapeutic potential for lung cancer suppression. Results obtained in this study suggested that FA-HPSPE with highly biocompatibility and targeting capability while forming complexes with shAkt1 and administrated through noninvasive aerosol could be prospective for inhibiting lung tumorigenesis. (C) 2016 Elsevier B.V. All rights reserved