Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

metabolomics; +16 new citations

Fri, 31/08/2018 - 16:52
16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/31PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +16 new citations

Fri, 31/08/2018 - 13:52
16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/31PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +20 new citations

Thu, 30/08/2018 - 15:50
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/30PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +20 new citations

Thu, 30/08/2018 - 12:46
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/30PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +18 new citations

Wed, 29/08/2018 - 18:38
18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/29PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +18 new citations

Wed, 29/08/2018 - 12:31
18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/29PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Metabolomics analysis reveals potential mechanisms of tolerance to excess molybdenum in soybean seedlings.

Tue, 28/08/2018 - 12:16
Metabolomics analysis reveals potential mechanisms of tolerance to excess molybdenum in soybean seedlings. Ecotoxicol Environ Saf. 2018 Aug 24;164:589-596 Authors: Xu S, Hu C, Hussain S, Tan Q, Wu S, Sun X Abstract Most plants exhibit strong tolerance to excess molybdenum (Mo). However, the metabolic profile and tolerance mechanisms of plants in response to excess Mo remain unknown. We comprehensively analyzed changes in the metabolic profiles of leaves and roots in soybean (Glycine max L.) seedlings cultured under normal-Mo and excess-Mo conditions by using ultra performance liquid chromatography (UPLC) combined with MS/MS (mass spectrometry). There were 42 differential metabolites in the roots and 19 differential metabolites in the leaves in response to excess Mo stress. In roots, the organic acids, levels of gluconic acid, D-glucarate and citric acid increased by 107.63-, 4.42- and 2.87-folds after excess Mo exposure. Several hormones (salicylic acid, jasmonic acid) and lipids (PG, MG, DG etc) also increased significantly under excess Mo condition. Metabolites related to ascorbate-glutathione metabolism and flavonoid and isoflavone biosynthesis notably accumulated in roots. Only lipid metabolism and salicylic acid accumulation were induced in leaves under excess Mo stress. It is speculated that organic compounds such as 2-oxoarginine, L-nicotine, gluconic acid, D-glucurate, and citric acid played important roles to chelate Mo and reduce its toxicity. Signaling molecules (JA, SA, and some lipids) and non-enzyme antioxidants such as flavonoids/isoflavones act synergistically to detoxify ROS and contribute to Mo tolerance in soybean seedlings. More metabolic pathways were induced by Mo excess in roots than in leaves, suggesting that roots play more implant role in Mo tolerance. PMID: 30149358 [PubMed - as supplied by publisher]

Metabolomics analysis reveals that elevated atmospheric CO2 alleviates drought stress in cucumber seedling leaves.

Tue, 28/08/2018 - 12:16
Metabolomics analysis reveals that elevated atmospheric CO2 alleviates drought stress in cucumber seedling leaves. Anal Biochem. 2018 Aug 24;: Authors: Li M, Li Y, Zhang W, Li S, Gao Y, Ai X, Zhang D, Liu B, Li Q Abstract Elevated atmospheric CO2 alleviates moderate to severe drought stresses at physiological level in cucumber. To investigate the underlying metabolic mechanisms, cucumber seedlings were treated with two [CO2] and three water treatments combinations, and their leaves were analyzed using a non-targeted metabolomics approach. The results showed that elevated [CO2] changed 79 differential metabolites which were mainly associated with alanine, aspartate and glutamate metabolism; arginine and proline metabolism; TCA cycle; and glycerophospholipid metabolism under moderate drought stress. Moreover, elevated [CO2] promoted the accumulation of secondary metabolites; including isoferulic acid, m-coumaric acid and salicyluric acid. Under severe drought stress, elevated [CO2] changed 26 differential metabolites which mainly involved in alanine, aspartate and glutamate metabolism; pyruvate metabolism; arginine and proline metabolism; glyoxylate and dicarboxylate metabolism; cysteine and methionine metabolism; starch and sucrose metabolism; glycolysis or gluconeogenesis; and pyrimidine metabolism. In addition, elevated [CO2] accumulated carbohydrates, 1,2,3-trihydroxybenzene, pyrocatechol, glutamate, and L-gulonolactone, to allow adaption to severe drought. In conclusion, the metabolites and metabolic pathways associated with the alleviation of drought stresses by elevated [CO2] were different according to the level of drought stress. Our results may provide a theoretical basis for CO2 fertilization and application of exogenous metabolites to enhance drought tolerance of cucumber. PMID: 30149025 [PubMed - as supplied by publisher]

Ion-pair selection method for pseudotargeted metabolomics based on SWATH MS acquisition and its application in differential metabolite discovery of Type 2 diabetes.

Tue, 28/08/2018 - 12:16
Ion-pair selection method for pseudotargeted metabolomics based on SWATH MS acquisition and its application in differential metabolite discovery of Type 2 diabetes. Anal Chem. 2018 Aug 27;: Authors: Wang L, Su B, Zeng Z, Li C, Zhao X, Lv W, Xuan Q, Ouyang Y, Zhou L, Yin P, Peng X, Lu X, Lin X, Xu G Abstract Pseudotargeted metabolomics method integrates advantages of non-targeted and targeted analysis because it can acquire data of metabolites in the multi-reaction monitoring (MRM) mode of mass spectrometry (MS) without needing standards. The key is the ion-pair information collection from samples to be analyzed. It is well known that sequential windowed acquisition of all theoretical Fragment ion (SWATH) MS mode can acquire MS2 information in a maximum extent. To expediently acquire as many ion-pairs as possible with optimal collision energy (CE), an ion-pair selection approach based on SWATH MS acquisition with variable isolation windows was developed in this study. Initially, non-targeted acquisition of all metabolites information in plasma Standard Reference Material (SRM 1950) was performed by ultra-performance liquid chromatography (UHPLC)-quadrupole time-of-flight (Q-TOF) MS platform with three CEs. With the help of software tool, the ion-pairs of unique metabolites were gained. Then they were validated in scheduled MRM coupled with UHPLC. After removing false positive, the ion-pairs with an optimal CE was integrated. A total of 1373 unique metabolite ion-pairs were obtained at positive ion mode. And repeatability of the established pseudotargeted approach was evaluated by intraday and interday precision. The results demonstrated the method was stable, reliable and suitable for metabolomics study. As an application example, alterations of serum metabolites in Type 2 diabetes were investigated by using the established method. This work provides a pseudotargeted ion-pair selection method based on SWATH MS acquisition with the characters of increased metabolite coverage, suitable CE and convenient processing. PMID: 30148611 [PubMed - as supplied by publisher]

Emerging role of metabolomics in rheumatology.

Tue, 28/08/2018 - 12:16
Related Articles Emerging role of metabolomics in rheumatology. Int J Rheum Dis. 2018 Aug;21(8):1468-1477 Authors: Gupta L, Ahmed S, Jain A, Misra R Abstract The pursuit for understanding disease pathogenesis, in this age of rapid laboratory diagnostics and fast-paced research, has led scientists worldwide to take recourse in hypothesis-free approaches for molecular diagnosis. Metabolomics is one such powerful tool that explores comprehensibly the metabolic alternations in human diseases. It involves study of small molecules of less than 1 kD in size by either LSMS or nuclear magnetic resonance. Unlike genomics, which tells us what may have happened, metabolomics reflects what did happen. The NMR technique has an advantage of analyzing metabolites without sample preparation, thereby diminishing artifacts, is less cumbersome and with the latest database on Metabolome; about 30 000 metabolites can be identified. The study of metabolomics for several rheumatic diseases, including rheumatoid arthritis, lupus, osteoarthritis and vasculitis, has revealed distinctive metabolic signatures. Thus, metabolomics is a technique that promises precision medicine with better biomarkers, robust predictors of drug response and of disease outcome, discovery of newer metabolites and pathways in disease pathogenesis, and finally, targeted drug development. This review intends to decipher its relevance in common rheumatic diseases. PMID: 30146741 [PubMed - in process]

Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis.

Tue, 28/08/2018 - 12:16
Related Articles Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis. Cell Metab. 2018 Aug 20;: Authors: Kalucka J, Bierhansl L, Conchinha NV, Missiaen R, Elia I, Brüning U, Scheinok S, Treps L, Cantelmo AR, Dubois C, de Zeeuw P, Goveia J, Zecchin A, Taverna F, Morales-Rodriguez F, Brajic A, Conradi LC, Schoors S, Harjes U, Vriens K, Pilz GA, Chen R, Cubbon R, Thienpont B, Cruys B, Wong BW, Ghesquière B, Dewerchin M, De Bock K, Sagaert X, Jessberger S, Jones EAV, Gallez B, Lambrechts D, Mazzone M, Eelen G, Li X, Fendt SM, Carmeliet P Abstract Little is known about the metabolism of quiescent endothelial cells (QECs). Nonetheless, when dysfunctional, QECs contribute to multiple diseases. Previously, we demonstrated that proliferating endothelial cells (PECs) use fatty acid β-oxidation (FAO) for de novo dNTP synthesis. We report now that QECs are not hypometabolic, but upregulate FAO >3-fold higher than PECs, not to support biomass or energy production but to sustain the tricarboxylic acid cycle for redox homeostasis through NADPH regeneration. Hence, endothelial loss of FAO-controlling CPT1A in CPT1AΔEC mice promotes EC dysfunction (leukocyte infiltration, barrier disruption) by increasing endothelial oxidative stress, rendering CPT1AΔEC mice more susceptible to LPS and inflammatory bowel disease. Mechanistically, Notch1 orchestrates the use of FAO for redox balance in QECs. Supplementation of acetate (metabolized to acetyl-coenzyme A) restores endothelial quiescence and counters oxidative stress-mediated EC dysfunction in CPT1AΔEC mice, offering therapeutic opportunities. Thus, QECs use FAO for vasculoprotection against oxidative stress-prone exposure. PMID: 30146488 [PubMed - as supplied by publisher]

Impairment of Angiogenesis by Fatty Acid Synthase Inhibition Involves mTOR Malonylation.

Tue, 28/08/2018 - 12:16
Related Articles Impairment of Angiogenesis by Fatty Acid Synthase Inhibition Involves mTOR Malonylation. Cell Metab. 2018 Aug 21;: Authors: Bruning U, Morales-Rodriguez F, Kalucka J, Goveia J, Taverna F, Queiroz KCS, Dubois C, Cantelmo AR, Chen R, Loroch S, Timmerman E, Caixeta V, Bloch K, Conradi LC, Treps L, Staes A, Gevaert K, Tee A, Dewerchin M, Semenkovich CF, Impens F, Schilling B, Verdin E, Swinnen JV, Meier JL, Kulkarni RA, Sickmann A, Ghesquière B, Schoonjans L, Li X, Mazzone M, Carmeliet P Abstract The role of fatty acid synthesis in endothelial cells (ECs) remains incompletely characterized. We report that fatty acid synthase knockdown (FASNKD) in ECs impedes vessel sprouting by reducing proliferation. Endothelial loss of FASN impaired angiogenesis in vivo, while FASN blockade reduced pathological ocular neovascularization, at >10-fold lower doses than used for anti-cancer treatment. Impaired angiogenesis was not due to energy stress, redox imbalance, or palmitate depletion. Rather, FASNKD elevated malonyl-CoA levels, causing malonylation (a post-translational modification) of mTOR at lysine 1218 (K1218). mTOR K-1218 malonylation impaired mTOR complex 1 (mTORC1) kinase activity, thereby reducing phosphorylation of downstream targets (p70S6K/4EBP1). Silencing acetyl-CoA carboxylase 1 (an enzyme producing malonyl-CoA) normalized malonyl-CoA levels and reactivated mTOR in FASNKD ECs. Mutagenesis unveiled the importance of mTOR K1218 malonylation for angiogenesis. This study unveils a novel role of FASN in metabolite signaling that contributes to explaining the anti-angiogenic effect of FASN blockade. PMID: 30146486 [PubMed - as supplied by publisher]

Direct screening of malonylginsenosides from nine Ginseng extracts by an untargeted profiling strategy incorporating in-source collision-induced dissociation, mass tag, and neutral loss scan on a hybrid linear ion-trap/Orbitrap mass spectrometer...

Tue, 28/08/2018 - 12:16
Related Articles Direct screening of malonylginsenosides from nine Ginseng extracts by an untargeted profiling strategy incorporating in-source collision-induced dissociation, mass tag, and neutral loss scan on a hybrid linear ion-trap/Orbitrap mass spectrometer coupled to ultra-high performance liquid chromatography. J Chromatogr A. 2018 Aug 11;: Authors: Shi X, Yang W, Huang Y, Hou J, Qiu S, Yao C, Feng Z, Wei W, Wu W, Guo D Abstract Specific analytical approaches that enable untargeted profiling of modified metabolites are in great need. An untargeted profiling strategy, by integrating in-source collision-induced dissociation (ISCID)-MS1, mass tag-MS2, and neutral loss scan-MS3, is established on a linear ion-trap/Orbitrap mass spectrometer coupled to ultra-high performance liquid chromatography. This strategy is applied to screen malonylginsenosides from three reputable Panax species (P. ginseng, P. quinquefolius, and P. notoginseng). In light of the preferred neutral elimination of CO2 and entire malonyl substituent (C3H2O3) in the negative electrospray ionization mode, a pseudo-neutral loss scan (PNL) method was established by applying ISCID energy 40 V in MS1, mass tag 43.9898 Da oriented CID-MS2 at normalized collision energy (NCE) 30%, and neutral loss 43.9898 Da-triggered high-energy C-trap dissociation-MS3 at NCE 70%. The PNL approach achieved a high coverage of targeted malonylginsenosides but introduced less false positives. It displayed comparable performance to a precursor ions list-driven targeted approach we have reported in the profiling and characterization of malonylginsenosides, but could avoid complex data processing. Totally 178 malonylginsenosides were characterized from the roots, leaves, and flower buds of P. ginseng, P. quinquefolius, and P. notoginseng, and most of them possess potentially new structures. The compositions of malonylginsenosides identified from these three Panax species are similar, and only malonylginsenoside Rb2 and some minor may have potential chemotaxonomic significance. In conclusion, we provide a potent analytical strategy for the direct and efficient screening of modified metabolites, which may have broad applications in the fields of metabolomics, drug metabolism, and natural product research. PMID: 30146372 [PubMed - as supplied by publisher]

Are we closer to the vision? A proposed framework for incorporating omics into environmental assessments.

Tue, 28/08/2018 - 12:16
Related Articles Are we closer to the vision? A proposed framework for incorporating omics into environmental assessments. Environ Toxicol Pharmacol. 2018 Apr;59:87-93 Authors: Martyniuk CJ Abstract Environmental science has benefited a great deal from omics-based technologies. High-throughput toxicology has defined adverse outcome pathways (AOPs), prioritized chemicals of concern, and identified novel actions of environmental chemicals. While many of these approaches are conducted under rigorous laboratory conditions, a significant challenge has been the interpretation of omics data in "real-world" exposure scenarios. Clarity in the interpretation of these data limits their use in environmental monitoring programs. In recent years, one overarching objective of many has been to address fundamental questions concerning experimental design and the robustness of data collected under the broad umbrella of environmental genomics. These questions include: (1) the likelihood that molecular profiles return to a predefined baseline level following remediation efforts, (2) how reference site selection in an urban environment influences interpretation of omics data and (3) what is the most appropriate species to monitor in the environment from an omics point of view. In addition, inter-genomics studies have been conducted to assess transcriptome reproducibility in toxicology studies. One lesson learned from inter-genomics studies is that there are core molecular networks that can be identified by multiple laboratories using the same platform. This supports the idea that "omics-networks" defined a priori may be a viable approach moving forward for evaluating environmental impacts over time. Both spatial and temporal variability in ecosystem structure is expected to influence molecular responses to environmental stressors, and it is important to recognize how these variables, as well as individual factor (i.e. sex, age, maturation), may confound interpretation of network responses to chemicals. This mini-review synthesizes the progress made towards adopting these tools into environmental monitoring and identifies future challenges to be addressed, as we move into the next era of high throughput sequencing. A conceptual framework for validating and incorporating molecular networks into environmental monitoring programs is proposed. As AOPs become more defined and their potential in environmental monitoring assessments becomes more recognized, the AOP framework may prove to be the conduit between omics and penultimate ecological responses for environmental risk assessments. PMID: 29549817 [PubMed - indexed for MEDLINE]

Energy-Protein Supplementation and Lactation Affect Fatty Acid Profile of Liver and Adipose Tissue of Dairy Cows.

Tue, 28/08/2018 - 12:16
Related Articles Energy-Protein Supplementation and Lactation Affect Fatty Acid Profile of Liver and Adipose Tissue of Dairy Cows. Molecules. 2018 Mar 09;23(3): Authors: Brzozowska AM, Lukaszewicz M, Oprzadek JM Abstract This article addresses the hypothesis that lactation stage, parity and energy-protein feed additive affect fatty acid composition of blood, liver and adipose tissue of cows. The experiment was conducted on 24 Polish Holstein-Friesian cows divided into two feeding groups. One group of cows was fed solely a total mixed ration, while the other group was fed a ration with the addition of 2 kg of energy-protein supplement per cow/day. During the experiment, the samples of liver, adipose tissue and blood were taken and their fatty acid compositions were determined. Analysis of variance was applied to fatty acid relative weight percentage to determine the effect of the stage of lactation, parity, and energy-protein supplement on the fatty acid composition of the tissues. Stage of lactation had a significant impact on the content of many fatty acids in all examined tissues. We found that parity had no effect on fatty acid composition of blood, whereas it significantly affected C16:1 c9 in liver, and C16:1 c9 and C18:0 in adipose tissue. Energy-protein supplement significantly affected the content of most fatty acids in blood (e.g., C18:1 t11 and C18:3 n-3) and liver (C18:3 n-3, both isomers of conjugated linolenic acid and n-3 fatty acids derived from fish oil), but it did not affect the profile of the adipose tissue of cows. According to our best knowledge, this is the first study showing the relationship between parity, stage of lactation and the composition of fatty acids in blood, liver and adipose tissue of cows. PMID: 29522430 [PubMed - indexed for MEDLINE]

Calycophyllum spruceanum (Benth.), the Amazonian "Tree of Youth" Prolongs Longevity and Enhances Stress Resistance in Caenorhabditis elegans.

Tue, 28/08/2018 - 12:16
Related Articles Calycophyllum spruceanum (Benth.), the Amazonian "Tree of Youth" Prolongs Longevity and Enhances Stress Resistance in Caenorhabditis elegans. Molecules. 2018 Feb 27;23(3): Authors: Peixoto H, Roxo M, Koolen H, da Silva F, Silva E, Braun MS, Wang X, Wink M Abstract The tree popularly known in Brazil as mulateiro or pau-mulato (Calycophyllum spruceanum (Benth.) K. Schum.) is deeply embedded in the herbal medicine of the Amazon region. Different preparations of the bark are claimed to have anti-aging, antioxidant, antimicrobial, emollient, wound healing, hemostatic, contraceptive, stimulant, and anti-diabetic properties. The current study aims to provide the first step towards a science-based evidence of the beneficial effects of C. spruceanum in the promotion of longevity and in the modulation of age-related markers. For this investigation, we used the model system Caenorhabditis elegans to evaluate in vivo antioxidant and anti-aging activity of a water extract from C. spruceanum. To chemically characterize the extract, HPLC MS (High Performance Liquid Chromatography Mass Spectrometry)/MS analyses were performed. Five secondary metabolites were identified in the extract, namely gardenoside, 5-hydroxymorin, cyanidin, taxifolin, and 5-hydroxy-6-methoxycoumarin-7-glucoside. C. spruceanum extract was able to enhance stress resistance and to extend lifespan along with attenuation of aging-associated markers in C. elegans. The demonstrated bioactivities apparently depend on the DAF-16/FOXO pathway. The data might support the popular claims of mulateiro as the "tree of youth", however more studies are needed to clarify its putative benefits to human health. PMID: 29495517 [PubMed - indexed for MEDLINE]

Black Tea Samples Origin Discrimination Using Analytical Investigations of Secondary Metabolites, Antiradical Scavenging Activity and Chemometric Approach.

Tue, 28/08/2018 - 12:16
Related Articles Black Tea Samples Origin Discrimination Using Analytical Investigations of Secondary Metabolites, Antiradical Scavenging Activity and Chemometric Approach. Molecules. 2018 Feb 26;23(3): Authors: Koch W, Kukula-Koch W, Komsta Ł Abstract A comprehensive study on the composition and antioxidant properties of black tea samples with a chemometric approach was performed via LC-ESI-Q-TOF-MS, DPPH radical scavenging assay, and Folin-Ciocalteu assay (TPC). Marked differences between the teas from seven different countries (China, India, Iran, Japan, Kenya, Nepal, Sri Lanka) were shown. The Indian samples demonstrated the highest total catechin content (184.8 mg/100 mL), the largest TPC and DPPH scavenging potential (58.2 mg/100 mL and 84.5%, respectively). The applied principal component analysis (PCA) and ANOVA revealed several correlations between the level of catechins in tea infusions. EC (epicatechin), ECG (epicatechin gallate), EGC (epigallocatechin), and EGCG (epigallocatechin-3-gallate) content was not correlated with DPPH, gallic acid, and TPC; however, a strong correlation of EC and ECG between themselves and a negative correlation of these two catechins with EGCG and EGC was noted. Interestingly, simple catechins were not found to be responsible for antioxidant properties of the black teas. The samples collected in the higher altitudes were similar. PMID: 29495365 [PubMed - indexed for MEDLINE]

Six genes of ompA family shuffling for development of polyvalent vaccines against Vibrio alginolyticus and Edwardsiella tarda.

Tue, 28/08/2018 - 12:16
Related Articles Six genes of ompA family shuffling for development of polyvalent vaccines against Vibrio alginolyticus and Edwardsiella tarda. Fish Shellfish Immunol. 2018 Apr;75:308-315 Authors: Cheng ZX, Chu X, Wang SN, Peng XX, Li H Abstract Polyvalent vaccines against more than one species of pathogens are especially important due to the complex ecosystem in aquaculture. We have previously shown that the development of polyvalent vaccines by shuffling six ompA genes from different bacteria with V. parahaemolyticus VP0764 primers. Here, we used the same 6 genes, V. alginolyticus VA0764 and VA1186, V. parahaemolyticus VP0764 and VP1186, E. tarda ompA and E. coli ompA, but with E. tarda ompA primers to develop new polyvalent vaccines. By this approach, we identified 7 potential polyvalent vaccines that were effective against both V. alginolyticus and E. tarda infections. Furthermore, the innate immunity triggered by the vaccines were also explored in three groups, no protection (group I), protection against V. alginolyticus (group II), and protection against both V. alginolyticus and E. tarda (group III). The transcription of IL-1β, IL-6, IL-8, C3b and NF-kB were significantly increased in group II and group III but not group I, where the expression level of group III was higher than group II. In addition, differential activities of succinate dehydrogenase were detected among the three groups. These results indicate the expansion of polyvalent vaccine reservoir with the same shuffling genes but different primers, and promote the understanding of the mechanisms of polyvalent vaccines based on vaccine-induced innate immunity. PMID: 29438846 [PubMed - indexed for MEDLINE]

Associations Between CagA, VacA, and the Clinical Outcomes of Helicobacter Pylori Infections in Okinawa, Japan.

Tue, 28/08/2018 - 12:16
Related Articles Associations Between CagA, VacA, and the Clinical Outcomes of Helicobacter Pylori Infections in Okinawa, Japan. Kobe J Med Sci. 2017 Nov 22;63(2):E58-E67 Authors: Inagaki T, Nishiumi S, Ito Y, Yamakawa A, Yamazaki Y, Yoshida M, Azuma T Abstract Helicobacter pylori, which is involved in the pathogenesis of gastroduodenal disease, produces CagA and VacA as major virulence factors. CagA is classified into East Asian and Western types based on the number and sequences of its Glu-Pro-Ile-Tyr-Ala motifs. The vacA gene has three polymorphic regions: the signal (s), intermediate (i), and middle (m) regions. The lowest gastric cancer mortality rate is seen in Okinawa. On the Japanese mainland (Honshu), most H. pylori produce s1/m1-VacA, which exhibits strong toxicity, and East Asian-type CagA. However, the H. pylori detected in Okinawa produces s1/m2-VacA, which exhibits weak toxicity, or s2/m2-VacA, which is non-toxic, and Western-type CagA. Studies about the i-region of vacA have been performed around the world, but there have been few such studies in Japan. Therefore, the aim of this study was to assess the relationships between the clinical outcomes of H. pylori infections in Okinawa, vacA (especially the i-region genotype), and cagA. H. pylori strains that were collected from patients with gastric cancer or gastric ulcers in Okinawa only produced the i1-type VacA virulence factor. The vacuolating cytotoxin activity of i1-type VacA was stronger than that of i2-type VacA, suggesting that the i-region genotype of vacA is closely associated with vacuolating cytotoxin activity. These results indicate that the i-region genotype of vacA is a useful marker of both H. pylori virulence and the clinical outcomes of H. pylori infections in Okinawa, Japan. PMID: 29434176 [PubMed - indexed for MEDLINE]

Effects of perinatal exposure to BPA and its alternatives (BPS, BPF and BPAF) on hepatic lipid and glucose homeostasis in female mice adolescent offspring.

Mon, 27/08/2018 - 15:03
Related Articles Effects of perinatal exposure to BPA and its alternatives (BPS, BPF and BPAF) on hepatic lipid and glucose homeostasis in female mice adolescent offspring. Chemosphere. 2018 Aug 17;212:297-306 Authors: Meng Z, Wang D, Yan S, Li R, Yan J, Teng M, Zhou Z, Zhu W Abstract The widespread application of bisphenols (BPs) makes them ubiquitous in the natural environment and poses many potential risks. In this study, we examined the effects of perinatal exposure to BPA and its 3 alternatives (BPS, BPF, and BPAF) on lipid and glucose homeostasis in female mice adolescent offspring. Specifically, BPA exposure promoted the expression of hepatic lipid synthesis and fatty acid accumulation genes, resulting in a significant increase in 2 free fatty acids contents. BPS exposure caused an increase in 6 free fatty acids and triglyceride contents through promoting the expression of fatty acid synthesis, triglyceride synthesis and fatty acid accumulation genes and inhibiting the expression of fatty acid β-oxidation genes. Interestingly, BPAF exposure showed completely opposite effects on hepatic lipid metabolism compared to BPS exposure. 9 free fatty acids and triglycerides contents in the liver were significantly reduced. In particular, BPF exposure caused decreases in 2 free fatty acids contents, but no significant changes were found in the genes for lipid metabolism. In addition, unlike BPA and BPF exposure, BPS and BPAF exposure also resulted in significant increases in glucose and glycogen contents in the liver by activation of Fxr-Shp pathway and glycolysis, and inhibition of gluconeogenesis. The results showed that compared to BPA and BPF exposure, BPS and BPAF exposure significantly regulated the expression of genes related to glucose and lipid metabolism and severely interfered with hepatic lipid and glucose homeostasis. This suggested that we should thoroughly evaluate the potential health risks of BPA and its alternatives. PMID: 30145421 [PubMed - as supplied by publisher]

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