(1S,3R)-3-Ammonio­cyclo­hexa­necarboxyl­ate

The title γ-amino­butyric acid, C7H13NO2, exists as a zwitterion. The crystal structure is stabilized by a network of inter­molecular N—H⋯O hydrogen bonds, forming a two-dimensional bilayer. An inter­molecular C—H⋯O hydrogen bond is also observed

Chemical proteomic analysis of the potential toxicological mechanisms of microcystin-RR in zebrafish (Danio rerio) liver

Microcystins (MCs) are common toxins produced by freshwater cyanobacteria, and they represent a potential health risk to aquatic organisms and animals, including humans. Specific inhibition of protein phosphatases 1 and 2A is considered the typical mechanism of MCs toxicity, but the exact mechanism has not been fully elucidated. To further our understanding of the toxicological mechanisms induced by MCs, this study is the first to use a chemical proteomic approach to screen proteins that exhibit special interactions with MC-arginine-arginine (MC-RR) from zebrafish (Danio rerio) liver. Seventeen proteins were identified via affinity blocking test. Integration of the results of previous studies and this study revealed that these proteins play a crucial role in various toxic phenomena of liver induced by MCs, such as the disruption of cytoskeleton assembly, oxidative stress, and metabolic disorder. Moreover, in addition to inhibition of protein phosphate activity, the overall toxicity of MCs was simultaneously modulated by the distribution of MCs in cells and their interactions with other target proteins. These results provide new insight into the mechanisms of hepatotoxicity induced by MCs. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1206-1216, 2016.</p

MicroRNA and Lung Cancer: A Mini Review

MicroRNAs (miRNAs) a class of non-coding RNAs about 22 nt in size that are found in a wide range of organisms from plants, viruses to humans. MicroRNA has a wide range of biological functions. It can recruit related RNA enzymes and lead to mRNA degradation after binding to mRNA specificity, thus blocking the expression of protein encoding genes and then affecting their biological functions. In recent years, microRNA has been found to be closely related to the biological behaviors, such as the occurrence, development, invasion and metastasis of multiple human malignant carcinomas, and play a regulatory role in the above biological phenotypes. Lung cancer is the highest incidence of malignancy. The exact molecular mechanism of its occurrence and development has not been fully elucidated. Previous studies have shown that microRNA plays an important role in lung tumor suppressor gene inactivation, oncogene activation and epigenetics. At the same time, there are also reports that there is a significant difference in the expression of microRNA in patients with lung cancer and benign lung diseases. This differential expression provides a basis for the feasibility of microRNA as a diagnostic and pre biological marker for lung cancer

Simultaneous quantitative determination of microcystin-LR and its glutathione metabolites in rat liver by liquid chromatography-tandem mass spectrometry

The roles of glutathione (GSH) and cysteine (Cys) in the detoxification of Microcystin-LR (MC-LR) have recently become a popular area of research. However, lacking analysis methods for MC-LR-GSH and MC-LR-Cys (two main GSH pathway metabolites) in mammals, elucidation of the detoxification mechanism and metabolic pathway of MC-LR in mammals is difficult. In this study, a novel method for the simultaneous quantitative analysis of MC-LR, MC-LR-GSH and MC-LR-Cys in rat liver was developed and validated. The analytes were simultaneously extracted from rat liver using 3 M sodium chloride solution containing 0.01 M EDTA-Na-2-5% acetic acid, followed by solid-phase extraction (SPE) on Oasis HLB and silica cartridges and determination by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS/MS). Under the optimized pretreatment conditions and instrument parameters, good recoveries of MC-LR, MC-LR-GSH and MC-LR-Cys were obtained at three concentrations (0.2, 1.0 and 2.5 mu g g(-1) dry weight (DW)) with values ranging from 97.7 +/- 4.2 to 98.7 +/- 5.1%, 70.1 +/- 4.8 to 71.1 +/- 4.1% and 79.8 +/- 3.5 to 81.4 +/- 4.0%, respectively. The relative standard deviations (RSDs) of these compounds at 0.2, 1.0 and 2.5 mu g g(-1) DW were between 4.3% and 6.9%. The limits of detection (LODs) were 0.005, 0.007 and 0.006 mu g g(-1) DW and the limits of quantification (LOQs) were 0,017, 0.023 and 0.020 mu g g(-1) DW for MC-LR, MC-LR-GSH and MC-LR-Cys, respectively. Furthermore, this method was successfully applied to both time- and dosage-effect studies of MC-LR, MC-LR-GSH and MC-LR-Cys in vivo. (C) 2014 Elsevier B.V. All rights reserved

Epidemiology characteristics of human coronaviruses in patients with respiratory infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010-2015 in Guangzhou.

Human coronavirus (HCoV) is one of the most common causes of respiratory tract infection throughout the world. To investigate the epidemiological and genetic variation of HCoV in Guangzhou, south China, we collected totally 13048 throat and nasal swab specimens from adults and children with fever and acute upper respiratory infection symptoms in Gunazhou, south China between July 2010 and June 2015, and the epidemiological features of HCoV and its species were studied. Specimens were screened for HCoV by real-time RT-PCR, and 7 other common respiratory viruses were tested simultaneously by PCR or real-time PCR. HCoV was detected in 294 cases (2.25%) of the 13048 samples, with most of them inpatients (251 cases, 85.4% of HCoV positive cases) and young children not in nursery (53.06%, 156 out of 294 HCoV positive cases). Four HCoVs, as OC43, 229E, NL63 and HKU1 were detected prevalent during 2010-2015 in Guangzhou, and among the HCoV positive cases, 60.20% were OC43, 16.67% were 229E, 14.97% were NL63 and 7.82% were HKU1. The month distribution showed that totally HCoV was prevalent in winter, but differences existed in different species. The 5 year distribution of HCoV showed a peak-valley distribution trend, with the detection rate higher in 2011 and 2013 whereas lower in 2010, 2012 and 2014. The age distribution revealed that children (especially those 50 years) were both high risk groups to be infected by HCoV. Of the 294 HCoV positive patients, 34.69% (101 cases) were co-infected by other common respiratory viruses, and influenza virus was the most common co-infecting virus (30/101, 29.70%). Fifteen HCoV-OC43 positive samples of 2013-2014 were selected for S gene sequencing and phylogenetic analysis, and the results showed that the 15 strains could be divided into 2 clusters in the phylogenetic tree, 12 strains of which formed a separate cluster that was closer to genotype G found in Malaysia. It was revealed for the first time that genotype B and genotype G of HCoV-OC43 co-circulated and the newly defined genotype G was epidemic as a dominant genotype during 2013-2014 in Guanzhou, south China

Why mammals more susceptible to the hepatotoxic microcystins than fish: evidences from plasma and albumin protein binding through equilibrium dialysis

To elucidate the interspecies variation of susceptibility to microcystins (MCs), fresh plasma and purified albumin from six kinds of mammals and fish were used in toxins-substances binding test. Protein contents in the test plasma were analyzed and the binding characteristics to MCs were compared. Two kinds of widely observed MCs, microcystin-LR (MC-LR) and microcystin-RR (MC-RR) were tested and data were collected through the method of equilibrium dialysis. It was found that total plasma protein and albumin content in mammals were nearly two times and four times higher than that in fish, respectively. In the test range of 0-100 mu g/mL, binding rates of fish plasma to MCs were considered significant lower (p &lt; 0.01) than that of mammals. And human plasma demonstrated the highest binding rate in mammals. In all the test species, plasma protein binding rates of MC-RR were significantly higher than MC-LR (p &lt; 0.01). Besides, binding profiles of albumin were acquired under the protein content of 0.67 mg/mL. Human serum albumin demonstrated the highest affinity to MCs throughout the six species and differences among the other five species were considered not significant (p &gt; 0.05). From the view of protein binding, it is concluded that both the variation of plasma protein composition and albumin binding characteristic could influence the existing form of MCs in circulation, change MCs utilization, alter MCs half-life and further contribute to the difference of susceptibility between mammals and fish.To elucidate the interspecies variation of susceptibility to microcystins (MCs), fresh plasma and purified albumin from six kinds of mammals and fish were used in toxins-substances binding test. Protein contents in the test plasma were analyzed and the binding characteristics to MCs were compared. Two kinds of widely observed MCs, microcystin-LR (MC-LR) and microcystin-RR (MC-RR) were tested and data were collected through the method of equilibrium dialysis. It was found that total plasma protein and albumin content in mammals were nearly two times and four times higher than that in fish, respectively. In the test range of 0-100 mu g/mL, binding rates of fish plasma to MCs were considered significant lower (p 0.05). From the view of protein binding, it is concluded that both the variation of plasma protein composition and albumin binding characteristic could influence the existing form of MCs in circulation, change MCs utilization, alter MCs half-life and further contribute to the difference of susceptibility between mammals and fish

Rapid conversion and reversible conjugation of glutathione detoxification of microcystins in bighead carp (Aristich-thys nobilis)

The glutathione and cysteine conjugates of microcystin (MC-GSH and MC-Cys, respectively) are two important metabolites in the detoxification of microcystins (MCs). Although studies have quantitated both conjugates, the reason why the amounts of MC-GSH are much lower than those of MC-Cys in various animal organs remains unknown. In this study, MC-RR-GSH and MC-RR-Cys were respectively i.p. injected into the cyanobacteria-eating bighead carp (Aristichthys nobilis), to explore the biotransformation and detoxification mechanisms of the two conjugates. The contents of MC-RR, MC-RR-GSH, MC-RR-Cys and MC-RR-N-acetyl-cysteine (MC-RR-Nac, the acetylation product of MC-RR-Cys) in the liver, kidney, intestine and blood of bighead carp in both groups were quantified via liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). In the MC-RR-GSH-treated group, the MC-RR-Cys content in the kidney increased 96.7-fold from 0.25 to 0.5 h post-injection, demonstrating that MC-RR-GSH acts as a highly reactive intermediate and is rapidly converted to MC-RR-Cys. The presence of MC-RR in both MC-RR-GSH- and MC-RR-Cys-treated groups indicates, for the first time, that MC conjugation with the thiol of GSH/Cys is a reversible process in vivo. Total MC-RR concentrations dissociated from MC-RR-Cys were lower than those from MC-RR-GSH, suggesting that MC-RR-Cys is more capable of detoxifying MC-RR. MC-RR-Cys was the most effectively excreted form in both the kidney and intestine, as the ratios of MC-RR-Cys to MC-RR reached as high as 15.2,2.9 in the MC-RR-GSH-treated group and 63.4, 19.1 in the MC-RR-Cys-treated group. Whereas MC-RR-Nac could not be found in all of the samples of the present study. Our results indicate that MC-RR-GSH was rapidly converted to MC-RR-Cys and then excreted, and that both glutathione and cysteine conjugates could release MC-RR. This study quantitatively proves the importance of the GSH detoxification pathway and furthers our understanding of the biochemical mechanism by which bighead carp are resistant to toxic cyanobacteria. (C) 2014 Elsevier B.V. All rights reserved.The glutathione and cysteine conjugates of microcystin (MC-GSH and MC-Cys, respectively) are two important metabolites in the detoxification of microcystins (MCs). Although studies have quantitated both conjugates, the reason why the amounts of MC-GSH are much lower than those of MC-Cys in various animal organs remains unknown. In this study, MC-RR-GSH and MC-RR-Cys were respectively i.p. injected into the cyanobacteria-eating bighead carp (Aristichthys nobilis), to explore the biotransformation and detoxification mechanisms of the two conjugates. The contents of MC-RR, MC-RR-GSH, MC-RR-Cys and MC-RR-N-acetyl-cysteine (MC-RR-Nac, the acetylation product of MC-RR-Cys) in the liver, kidney, intestine and blood of bighead carp in both groups were quantified via liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). In the MC-RR-GSH-treated group, the MC-RR-Cys content in the kidney increased 96.7-fold from 0.25 to 0.5 h post-injection, demonstrating that MC-RR-GSH acts as a highly reactive intermediate and is rapidly converted to MC-RR-Cys. The presence of MC-RR in both MC-RR-GSH- and MC-RR-Cys-treated groups indicates, for the first time, that MC conjugation with the thiol of GSH/Cys is a reversible process in vivo. Total MC-RR concentrations dissociated from MC-RR-Cys were lower than those from MC-RR-GSH, suggesting that MC-RR-Cys is more capable of detoxifying MC-RR. MC-RR-Cys was the most effectively excreted form in both the kidney and intestine, as the ratios of MC-RR-Cys to MC-RR reached as high as 15.2,2.9 in the MC-RR-GSH-treated group and 63.4, 19.1 in the MC-RR-Cys-treated group. Whereas MC-RR-Nac could not be found in all of the samples of the present study. Our results indicate that MC-RR-GSH was rapidly converted to MC-RR-Cys and then excreted, and that both glutathione and cysteine conjugates could release MC-RR. This study quantitatively proves the importance of the GSH detoxification pathway and furthers our understanding of the biochemical mechanism by which bighead carp are resistant to toxic cyanobacteria. (C) 2014 Elsevier B.V. All rights reserved