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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 20 min 55 sec ago

Heat stress response in the closest algal relatives of land plants reveals conserved stress signaling circuits.

Sun, 26/04/2020 - 12:19
Related Articles Heat stress response in the closest algal relatives of land plants reveals conserved stress signaling circuits. Plant J. 2020 Apr 24;: Authors: de Vries J, de Vries S, Curtis BA, Zhou H, Penny S, Feussner K, Pinto DM, Steinert M, Cohen A, von Schwartzenberg K, Archibald JM Abstract All land plants (embryophytes) share a common ancestor that likely evolved from a filamentous freshwater alga. Elucidating the transition from algae to embryophytes-and the eventual conquering of Earth's surface-is one of the most fundamental questions in plant evolutionary biology. Here, we investigated one of the organismal properties that might have enabled this transition: resistance to drastic temperature shifts. We explored the effect of heat stress in Mougeotia and Spirogyra, two representatives of Zygnematophyceae-the closest known algal sister lineage to land plants. Heat stress induced pronounced phenotypic alterations of their plastids, and HPLC-MS/MS-based profiling of 565 transitions for the analysis of main central metabolites revealed significant shifts in 43 compounds. We also analyzed the global differential gene expression responses triggered by heat, generating 92.8 Gbp of sequence data and assembling a combined set of 8,905 well-expressed genes. Each organism had its own distinct gene expression profile; less than half of their shared genes showed concordant gene expression trends. We nevertheless detected common signature responses to heat such as elevated transcript levels for molecular chaperones, thylakoid components, and-corroborating our metabolomic data-amino acid metabolism. We also uncovered the heat-stress responsiveness of genes for phosphorelay-based signal transduction that link environmental cues, calcium signatures and plastid biology. Our data allow us to infer the molecular heat stress response that the earliest land plants might have used when facing the rapidly shifting temperature conditions of the terrestrial habitat. PMID: 32333477 [PubMed - as supplied by publisher]

Identifying the compounds that can distinguish between Saposhnikovia root and its substitute, Peucedanum ledebourielloides root, using LC-HR/MS metabolomics.

Sun, 26/04/2020 - 12:19
Related Articles Identifying the compounds that can distinguish between Saposhnikovia root and its substitute, Peucedanum ledebourielloides root, using LC-HR/MS metabolomics. J Nat Med. 2020 Apr 24;: Authors: Yoshitomi T, Wakana D, Uchiyama N, Tsujimoto T, Kawano N, Yokokura T, Yamamoto Y, Fuchino H, Hakamatsuka T, Komatsu K, Kawahara N, Maruyama T Abstract Previously, we established a 1H NMR metabolomics method using reversed-phase solid-phase extraction column (RP-SPEC), and succeeded in distinguishing wild from cultivated samples of Saposhnikoviae radix (SR), and between SR and its substitute, Peucedanum ledebourielloides root (PR). Herein, we performed LC-HR/MS metabolomics using fractions obtained via RP-SPEC to identify characteristic components of SR and PR. One and three characteristic components were respectively found for SR and PR; these components were isolated with their m/z values and retention times as a guide. The characteristic component of SR was identified as 4'-O-β-D-glucosyl-5-O-methylvisamminol (1), an indicator component used to identify SR in the Japanese Pharmacopoeia. In contrast, the characteristic components of PR were identified as xanthalin (2), 4'-O-β-D-apiosyl (1 → 6)-β-D-glucosyl-5-O-methylvisamminol (3), and 3'-O-β-D-apiosyl (1 → 6)-β-D-glucosylhamaudol (4) based on spectroscopic data such as 1D- and 2D-NMR, MS, and specific optical rotation. Among them, 4 is a novel compound. For the correlation between the NMR metabolomics results in the present and our previous report, only 1 and 2 were found to correlate with the chemical shifts, and the other compounds had no correlation. As the chemical shifts for compounds 1, 3, and 4 were similar to each other, especially for the aglycone moiety, they could not be distinguished because of the sensitivity and resolution of 1H NMR. Accordingly, combining NMR and LC/MS metabolomics with their different advantages is considered useful for metabolomics of natural products. The series of methods used in our reports could aid in quality evaluations of natural products and surveying of marker components. PMID: 32333306 [PubMed - as supplied by publisher]

Targeted metabolomics highlights perturbed metabolism in the brain of autism spectrum disorder sufferers.

Sun, 26/04/2020 - 12:19
Related Articles Targeted metabolomics highlights perturbed metabolism in the brain of autism spectrum disorder sufferers. Metabolomics. 2020 Apr 24;16(5):59 Authors: Graham SF, Turkoglu O, Yilmaz A, Ustun I, Ugur Z, Bjorndhal T, Han B, Mandal R, Wishart D, Bahado-Singh RO Abstract INTRODUCTION: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficiencies in social interactions and communication, combined with restricted and repetitive behavioral issues. OBJECTIVES: As little is known about the etiopathophysiology of ASD and early diagnosis is relatively subjective, we aim to employ a targeted, fully quantitative metabolomics approach to biochemically profile post-mortem human brain with the overall goal of identifying metabolic pathways that may have been perturbed as a result of the disease while uncovering potential central diagnostic biomarkers. METHODS: Using a combination of 1H NMR and DI/LC-MS/MS we quantitatively profiled the metabolome of the posterolateral cerebellum from post-mortem human brain harvested from people who suffered with ASD (n = 11) and compared them with age-matched controls (n = 10). RESULTS: We accurately identified and quantified 203 metabolites in post-mortem brain extracts and performed a metabolite set enrichment analyses identifying 3 metabolic pathways as significantly perturbed (p < 0.05). These include Pyrimidine, Ubiquinone and Vitamin K metabolism. Further, using a variety of machine-based learning algorithms, we identified a panel of central biomarkers (9-hexadecenoylcarnitine (C16:1) and the phosphatidylcholine PC ae C36:1) capable of discriminating between ASD and controls with an AUC = 0.855 with a sensitivity and specificity equal to 0.80 and 0.818, respectively. CONCLUSION: For the first time, we report the use of a multi-platform metabolomics approach to biochemically profile brain from people with ASD and report several metabolic pathways which are perturbed in the diseased brain of ASD sufferers. Further, we identified a panel of biomarkers capable of distinguishing ASD from control brains. We believe that these central biomarkers may be useful for diagnosing ASD in more accessible biomatrices. PMID: 32333121 [PubMed - as supplied by publisher]

Metabolic changes in early neonatal life: NMR analysis of the neonatal metabolic profile to monitor postnatal metabolic adaptations.

Sun, 26/04/2020 - 12:19
Related Articles Metabolic changes in early neonatal life: NMR analysis of the neonatal metabolic profile to monitor postnatal metabolic adaptations. Metabolomics. 2020 Apr 24;16(5):58 Authors: Georgakopoulou I, Chasapi SA, Bariamis SE, Varvarigou A, Spraul M, Spyroulias GA Abstract BACKGROUND: A major challenge from the moment a child is delivered is the adaptation to the extrauterine life, where rapid metabolic changes take place. The study of these changes during the first days of human life may assist in the understanding of the metabolic processes that occur at this critical period, which is likely to provide significant clinical insights. To date, metabolomics has become a powerful field, ideal for the monitoring of such dynamic variations, since it offers the possibility to identify alterations in metabolic profiles, even on daily basis. METHODS: The study included 253 healthy newborns (GA 35 to 40 weeks) from the region of Western Greece. Urine samples were collected immediately after birth and at the third day of life. NMR-based metabolomics was used to compare the metabolic urinary profiles of newborns from the first and third day of their life, assessing the impact of six perinatal factors; delivery mode, prematurity, maternal smoking, gender, nutrition and neonatal jaundice. RESULTS: Analysis of urine metabolic fingerprint from the first and third day of life, coupled with multivariate statistics, provides insights into the details of early life metabolic profile differentiation. Αt the third day of life metabolic adaptations are evident, as many differences were noted in urine of healthy neonates within the first 72 h postpartum. Trends in differentiation of metabolites levels between the two groups, late preterm and term newborns, have been also observed. CONCLUSIONS: Newborn's urine metabolic profiles confirmed the rapid changes in their metabolism after birth. Further, ongoing research will enable us to develop one reference model of urinary metabolomics in healthy newborns during the period of adaptation to the extra-uterine life. PMID: 32333120 [PubMed - as supplied by publisher]

Biological sex and DNA repair deficiency drive Alzheimer's disease via systemic metabolic remodeling and brain mitochondrial dysfunction.

Sun, 26/04/2020 - 12:19
Related Articles Biological sex and DNA repair deficiency drive Alzheimer's disease via systemic metabolic remodeling and brain mitochondrial dysfunction. Acta Neuropathol. 2020 Apr 24;: Authors: Demarest TG, Varma VR, Estrada D, Babbar M, Basu S, Mahajan UV, Moaddel R, Croteau DL, Thambisetty M, Mattson MP, Bohr VA Abstract Alzheimer's disease (AD) is an incurable neurodegenerative disease that is more prevalent in women. The increased risk of AD in women is not well understood. It is well established that there are sex differences in metabolism and that metabolic alterations are an early component of AD. We utilized a cross-species approach to evaluate conserved metabolic alterations in the serum and brain of human AD subjects, two AD mouse models, a human cell line, and two Caenorhabditis elegans AD strains. We found a mitochondrial complex I-specific impairment in cortical synaptic brain mitochondria in female, but not male, AD mice. In the hippocampus, Polβ haploinsufficiency caused synaptic complex I impairment in male and female mice, demonstrating the critical role of DNA repair in mitochondrial function. In non-synaptic, glial-enriched, mitochondria from the cortex and hippocampus, complex II-dependent respiration increased in female, but not male, AD mice. These results suggested a glial upregulation of fatty acid metabolism to compensate for neuronal glucose hypometabolism in AD. Using an unbiased metabolomics approach, we consistently observed evidence of systemic and brain metabolic remodeling with a shift from glucose to lipid metabolism in humans with AD, and in AD mice. We determined that this metabolic shift is necessary for cellular and organismal survival in C. elegans, and human cell culture AD models. We observed sex-specific, systemic, and brain metabolic alterations in humans with AD, and that these metabolite changes significantly correlate with amyloid and tau pathology. Among the most significant metabolite changes was the accumulation of glucose-6-phosphate in AD, an inhibitor of hexokinase and rate-limiting metabolite for the pentose phosphate pathway (PPP). Overall, we identified novel mechanisms of glycolysis inhibition, PPP, and tricarboxylic acid cycle impairment, and a neuroprotective augmentation of lipid metabolism in AD. These findings support a sex-targeted metabolism-modifying strategy to prevent and treat AD. PMID: 32333098 [PubMed - as supplied by publisher]

Modification of an atmospheric pressure photoionization source for online analysis of exhaled breath coupled with quadrupole time-of-flight mass spectrometry.

Sun, 26/04/2020 - 12:19
Related Articles Modification of an atmospheric pressure photoionization source for online analysis of exhaled breath coupled with quadrupole time-of-flight mass spectrometry. Anal Bioanal Chem. 2020 Apr 25;: Authors: Zhou W, Huang C, Zou X, Lu Y, Xia L, Shen C, Chu Y Abstract Breath analysis is a promising method for metabolomics studies and clinical diagnosis, as it enables the observation of metabolites in a convenient and noninvasive way. In this work, an atmospheric pressure photoionization (APPI) source was modified for online analysis of exhaled breath by coupling with quadrupole time-of-flight mass spectrometry (QTOFMS). Three parameters, namely, the capillary voltage, the sampling flow and the curtain gas flow of the APPI source, were optimized. Five healthy volunteers, three males and two females, were enrolled to test the performance of modified APPI-QTOFMS by analyzing their exhaled breath. A total of 21 compounds were tentatively identified, and four metabolites, namely, dimethyl selenoxide, δ-valerolactam, hydroxymandelic acid and palmitic amide were detected in the exhaled breath for the first time. The result shows that modified APPI-QTOFMS can be used for the online study of exhaled breath. Graphical abstract. PMID: 32333078 [PubMed - as supplied by publisher]

Global injury morbidity and mortality from 1990 to 2017: results from the Global Burden of Disease Study 2017.

Sun, 26/04/2020 - 12:19
Related Articles Global injury morbidity and mortality from 1990 to 2017: results from the Global Burden of Disease Study 2017. Inj Prev. 2020 Apr 24;: Authors: James SL, Castle CD, Dingels ZV, Fox JT, Hamilton EB, Liu Z, S Roberts NL, Sylte DO, Henry NJ, LeGrand KE, Abdelalim A, Abdoli A, Abdollahpour I, Abdulkader RS, Abedi A, Abosetugn AE, Abushouk AI, Adebayo OM, Agudelo-Botero M, Ahmad T, Ahmed R, Ahmed MB, Eddine Aichour MT, Alahdab F, Alamene GM, Alanezi FM, Alebel A, Alema NM, Alghnam SA, Al-Hajj S, Ali BA, Ali S, Alikhani M, Alinia C, Alipour V, Aljunid SM, Almasi-Hashiani A, Almasri NA, Altirkawi K, Abdeldayem Amer YS, Amini S, Loreche Amit AM, Andrei CL, Ansari-Moghaddam A, T Antonio CA, Yaw Appiah SC, Arabloo J, Arab-Zozani M, Arefi Z, Aremu O, Ariani F, Arora A, Asaad M, Asghari B, Awoke N, Ayala Quintanilla BP, Ayano G, Ayanore MA, Azari S, Azarian G, Badawi A, Badiye AD, Bagli E, Baig AA, Bairwa M, Bakhtiari A, Balachandran A, Banach M, Banerjee SK, Banik PC, Banstola A, Barker-Collo SL, Bärnighausen TW, Barrero LH, Barzegar A, Bayati M, Baye BA, Bedi N, Behzadifar M, Bekuma TT, Belete H, Benjet C, Bennett DA, Bensenor IM, Berhe K, Bhardwaj P, Bhat AG, Bhattacharyya K, Bibi S, Bijani A, Bin Sayeed MS, Borges G, Borzì AM, Boufous S, Brazinova A, Briko NI, Budhathoki SS, Car J, Cárdenas R, Carvalho F, Castaldelli-Maia JM, Castañeda-Orjuela CA, Castelpietra G, Catalá-López F, Cerin E, Chandan JS, Chanie WF, Chattu SK, Chattu VK, Chatziralli I, Chaudhary N, Cho DY, Kabir Chowdhury MA, Chu DT, Colquhoun SM, Constantin MM, Costa VM, Damiani G, Daryani A, Dávila-Cervantes CA, Demeke FM, Demis AB, Demoz GT, Demsie DG, Derakhshani A, Deribe K, Desai R, Nasab MD, da Silva DD, Dibaji Forooshani ZS, Doyle KE, Driscoll TR, Dubljanin E, Adema BD, Eagan AW, Eftekhari A, Ehsani-Chimeh E, Sayed Zaki ME, Elemineh DA, El-Jaafary SI, El-Khatib Z, Ellingsen CL, Emamian MH, Endalew DA, Eskandarieh S, Faris PS, Faro A, Farzadfar F, Fatahi Y, Fekadu W, Ferede TY, Fereshtehnejad SM, Fernandes E, Ferrara P, Feyissa GT, Filip I, Fischer F, Folayan MO, Foroutan M, Francis JM, Franklin RC, Fukumoto T, Geberemariyam BS, Gebre AK, Gebremedhin KB, Gebremeskel GG, Gebremichael B, Gedefaw GA, Geta B, Ghafourifard M, Ghamari F, Ghashghaee A, Gholamian A, Gill TK, Goulart AC, Grada A, Grivna M, Mohialdeen Gubari MI, Guimarães RA, Guo Y, Gupta G, Haagsma JA, Hafezi-Nejad N, Bidgoli HH, Hall BJ, Hamadeh RR, Hamidi S, Haro JM, Hasan MM, Hasanzadeh A, Hassanipour S, Hassankhani H, Hassen HY, Havmoeller R, Hayat K, Hendrie D, Heydarpour F, Híjar M, Ho HC, Hoang CL, Hole MK, Holla R, Hossain N, Hosseinzadeh M, Hostiuc S, Hu G, Ibitoye SE, Ilesanmi OS, Ilic I, Ilic MD, Inbaraj LR, Indriasih E, Naghibi Irvani SS, Shariful Islam SM, Islam MM, Ivers RQ, Jacobsen KH, Jahani MA, Jahanmehr N, Jakovljevic M, Jalilian F, Jayaraman S, Jayatilleke AU, Jha RP, John-Akinola YO, Jonas JB, Joseph N, Joukar F, Jozwiak JJ, Jungari SB, Jürisson M, Kabir A, Kadel R, Kahsay A, Kalankesh LR, Kalhor R, Kamil TA, Kanchan T, Kapoor N, Karami M, Kasaeian A, Kassaye HG, Kavetskyy T, Kebede HK, Keiyoro PN, Kelbore AG, Kelkay B, Khader YS, Khafaie MA, Khalid N, Khalil IA, Khalilov R, Khammarnia M, Khan EA, Khan M, Khanna T, Khazaie H, Shadmani FK, Khundkar R, Kiirithio DN, Kim YE, Kim D, Kim YJ, Kisa A, Kisa S, Komaki H, M Kondlahalli SK, Korshunov VA, Koyanagi A, G Kraemer MU, Krishan K, Bicer BK, Kugbey N, Kumar V, Kumar N, Kumar GA, Kumar M, Kumaresh G, Kurmi OP, Kuti O, Vecchia C, Lami FH, Lamichhane P, Lang JJ, Lansingh VC, Laryea DO, Lasrado S, Latifi A, Lauriola P, Leasher JL, Huey Lee SW, Lenjebo TL, Levi M, Li S, Linn S, Liu X, Lopez AD, Lotufo PA, Lunevicius R, Lyons RA, Madadin M, El Razek MMA, Mahotra NB, Majdan M, Majeed A, Malagon-Rojas JN, Maled V, Malekzadeh R, Malta DC, Manafi N, Manafi A, Manda AL, Manjunatha N, Mansour-Ghanaei F, Mansouri B, Mansournia MA, Maravilla JC, March LM, Mason-Jones AJ, Masoumi SZ, Massenburg BB, Maulik PK, Meles GG, Melese A, Melketsedik ZA, N Memiah PT, Mendoza W, Menezes RG, Mengesha MB, Mengesha MM, Meretoja TJ, Meretoja A, Merie HE, Mestrovic T, Miazgowski B, Miazgowski T, Miller TR, Mini GK, Mirica A, Mirrakhimov EM, Mirzaei-Alavijeh M, Mithra P, Moazen B, Moghadaszadeh M, Mohamadi E, Mohammad Y, Mohammad KA, Darwesh AM, Gholi Mezerji NM, Mohammadian-Hafshejani A, Mohammadoo-Khorasani M, Mohammadpourhodki R, Mohammed S, Mohammed JA, Mohebi F, Molokhia M, Monasta L, Moodley Y, Moosazadeh M, Moradi M, Moradi G, Moradi-Lakeh M, Moradpour F, Morawska L, Velásquez IM, Morisaki N, Morrison SD, Mossie TB, Muluneh AG, Murthy S, Musa KI, Mustafa G, Nabhan AF, Nagarajan AJ, Naik G, Naimzada MD, Najafi F, Nangia V, Nascimento BR, Naserbakht M, Nayak V, Ndwandwe DE, Negoi I, Ngunjiri JW, Nguyen CT, Thi Nguyen HL, Nikbakhsh R, Anggraini Ningrum DN, Nnaji CA, Nyasulu PS, Ogbo FA, Oghenetega OB, Oh IH, Okunga EW, Olagunju AT, Olagunju TO, Bali AO, Onwujekwe OE, Asante KO, Orpana HM, Ota E, Otstavnov N, Otstavnov SS, A MP, Padubidri JR, Pakhale S, Pakshir K, Panda-Jonas S, Park EK, Patel SK, Pathak A, Pati S, Patton GC, Paulos K, Peden AE, Filipino Pepito VC, Pereira J, Pham HQ, Phillips MR, Pinheiro M, Polibin RV, Polinder S, Poustchi H, Prakash S, Angga Pribadi DR, Puri P, Syed ZQ, Rabiee M, Rabiee N, Radfar A, Rafay A, Rafiee A, Rafiei A, Rahim F, Rahimi S, Rahimi-Movaghar V, Rahman MA, Rajabpour-Sanati A, Rajati F, Rakovac I, Ranganathan K, Rao SJ, Rashedi V, Rastogi P, Rathi P, Rawaf S, Rawal L, Rawassizadeh R, Renjith V, N Renzaho AM, Resnikoff S, Rezapour A, Ribeiro AI, Rickard J, Rios González CM, Ronfani L, Roshandel G, Saad AM, Sabde YD, Sabour S, Saddik B, Safari S, Safari-Faramani R, Safarpour H, Safdarian M, Sajadi SM, Salamati P, Salehi F, Zahabi SS, Rashad Salem MR, Salem H, Salman O, Salz I, Samy AM, Sanabria J, Riera LS, Santric Milicevic MM, Sarker AR, Sarveazad A, Sathian B, Sawhney M, Sawyer SM, Saxena S, Sayyah M, Schwebel DC, Seedat S, Senthilkumaran S, Sepanlou SG, Seyedmousavi S, Sha F, Shaahmadi F, Shahabi S, Shaikh MA, Shams-Beyranvand M, Shamsizadeh M, Sharif-Alhoseini M, Sharifi H, Sheikh A, Shigematsu M, Shin JI, Shiri R, Siabani S, Sigfusdottir ID, Singh PK, Singh JA, Sinha DN, Smarandache CG, R Smith EU, Soheili A, Soleymani B, Soltanian AR, Soriano JB, Sorrie MB, Soyiri IN, Stein DJ, Stokes MA, Sufiyan MB, Rasul Suleria HA, Sykes BL, Tabarés-Seisdedos R, Tabb KM, Taddele BW, Tadesse DB, Tamiru AT, Tarigan IU, Tefera YM, Tehrani-Banihashemi A, Tekle MG, Tekulu GH, Tesema AK, Tesfay BE, Thapar R, Tilahune AB, Tlaye KG, Tohidinik HR, Topor-Madry R, Tran BX, Tran KB, Tripathy JP, Tsai AC, Car LT, Ullah S, Ullah I, Umar M, Unnikrishnan B, Upadhyay E, Uthman OA, Valdez PR, Vasankari TJ, Venketasubramanian N, Violante FS, Vlassov V, Waheed Y, Weldesamuel GT, Werdecker A, Wiangkham T, Wolde HF, Woldeyes DH, Wondafrash DZ, Wondmeneh TG, Wondmieneh AB, Wu AM, Yadav R, Yadollahpour A, Yano Y, Yaya S, Yazdi-Feyzabadi V, Yip P, Yisma E, Yonemoto N, Yoon SJ, Youm Y, Younis MZ, Yousefi Z, Yu Y, Yu C, Yusefzadeh H, Moghadam TZ, Zaidi Z, Zaman SB, Zamani M, Zamanian M, Zandian H, Zarei A, Zare F, Zhang ZJ, Zhang Y, Zodpey S, Dandona L, Dandona R, Degenhardt L, Dharmaratne SD, Hay SI, Mokdad AH, Reiner RC, Sartorius B, Vos T Abstract BACKGROUND: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. METHODS: We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). FINDINGS: In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). INTERPRETATION: Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care. PMID: 32332142 [PubMed - as supplied by publisher]

Gluten-free diet yesterday, today and tomorrow: Forecasting using Google Trends data.

Sun, 26/04/2020 - 12:19
Related Articles Gluten-free diet yesterday, today and tomorrow: Forecasting using Google Trends data. Arab J Gastroenterol. 2020 Apr 21;: Authors: Kamiński M, Nowak JK, Skonieczna-Żydecka K, Stachowska E PMID: 32332000 [PubMed - as supplied by publisher]

Regional metabolic signatures in the Ndufs4(KO) mouse brain implicate defective glutamate/α-ketoglutarate metabolism in mitochondrial disease.

Sun, 26/04/2020 - 12:19
Related Articles Regional metabolic signatures in the Ndufs4(KO) mouse brain implicate defective glutamate/α-ketoglutarate metabolism in mitochondrial disease. Mol Genet Metab. 2020 Apr 03;: Authors: Johnson SC, Kayser EB, Bornstein R, Stokes J, Bitto A, Park KY, Pan A, Sun G, Raftery D, Kaeberlein M, Sedensky MM, Morgan PG Abstract Leigh Syndrome (LS) is a mitochondrial disorder defined by progressive focal neurodegenerative lesions in specific regions of the brain. Defects in NDUFS4, a subunit of complex I of the mitochondrial electron transport chain, cause LS in humans; the Ndufs4 knockout mouse (Ndufs4(KO)) closely resembles the human disease. Here, we probed brain region-specific molecular signatures in pre-symptomatic Ndufs4(KO) to identify factors which underlie focal neurodegeneration. Metabolomics revealed that free amino acid concentrations are broadly different by region, and glucose metabolites are increased in a manner dependent on both region and genotype. We then tested the impact of the mTOR inhibitor rapamycin, which dramatically attenuates LS in Ndufs4(KO), on region specific metabolism. Our data revealed that loss of Ndufs4 drives pathogenic changes to CNS glutamine/glutamate/α-ketoglutarate metabolism which are rescued by mTOR inhibition Finally, restriction of the Ndufs4 deletion to pre-synaptic glutamatergic neurons recapitulated the whole-body knockout. Together, our findings are consistent with mTOR inhibition alleviating disease by increasing availability of α-ketoglutarate, which is both an efficient mitochondrial complex I substrate in Ndufs4(KO) and an important metabolite related to neurotransmitter metabolism in glutamatergic neurons. PMID: 32331968 [PubMed - as supplied by publisher]

Metabolite profile and consumer sensory acceptability of meat from lean Nellore and Angus × Nellore crossbreed cattle fed soybean oil.

Sun, 26/04/2020 - 12:19
Related Articles Metabolite profile and consumer sensory acceptability of meat from lean Nellore and Angus × Nellore crossbreed cattle fed soybean oil. Food Res Int. 2020 Jun;132:109056 Authors: Antonelo DS, Cônsolo NRB, Gómez JFM, Beline M, Goulart RS, Corte RRPS, Colnago LA, Schilling MW, Gerrard DE, Silva SL Abstract Thirty each Nellore (NEL) and crossbred Angus × Nellore (AxN) were used to evaluate the effect of feeding soybean oil (SBO) and breed on meat sensory acceptability and its relation to muscle metabolite profiles. Cattle were fed for 133 d on two different diets: 1) basal feedlot diet (CON) and 2) CON diet with 3.5% added SBO. No interactions between diet and genetic group were detected for any traits measured. Meat from animals fed SBO diet had lower overall liking, flavor, tenderness and juiciness scores compared to meat from animals fed CON diet. The four most important compounds differing between animals fed CON and SBO diets were betaine, glycerol, fumarate, and carnosine, suggesting that metabolic pathways such as glycerolipid metabolism; glycine, serine and threonine metabolism; glutamine and glutamate metabolism; valine, leucine and isoleucine biosynthesis; and alanine, aspartate and glutamate metabolism were affected by diets. Nellore beef had a higher overall liking and meat flavor scores than AxN beef. The four most important compounds differing between breeds were glycine, glucose, alanine, and carnosine, which may indicate that metabolic pathways such as glutathione metabolism; primary bile acid biosynthesis; alanine, aspartate and glutamate metabolism; and valine, leucine and isoleucine biosynthesis were affected by genetic groups. Meat carnosine, inosine monophosphate, glutamate, betaine, glycerol and creatinine levels were correlated with sensory acceptability scores. Meat metabolite profiles and sensory acceptability were differentially impacted by diet and breed. PMID: 32331638 [PubMed - as supplied by publisher]

A Data Set of 255,000 Randomly Selected and Manually Classified Extracted Ion Chromatograms for Evaluation of Peak Detection Methods.

Sun, 26/04/2020 - 12:19
Related Articles A Data Set of 255,000 Randomly Selected and Manually Classified Extracted Ion Chromatograms for Evaluation of Peak Detection Methods. Metabolites. 2020 Apr 22;10(4): Authors: Müller E, Huber C, Beckers LM, Brack W, Krauss M, Schulze T Abstract Non-targeted mass spectrometry (MS) has become an important method over recent years in the fields of metabolomics and environmental research. While more and more algorithms and workflows become available to process a large number of non-targeted data sets, there still exist few manually evaluated universal test data sets for refining and evaluating these methods. The first step of non-targeted screening, peak detection and refinement of it is arguably the most important step for non-targeted screening. However, the absence of a model data set makes it harder for researchers to evaluate peak detection methods. In this Data Descriptor, we provide a manually checked data set consisting of 255,000 EICs (5000 peaks randomly sampled from across 51 samples) for the evaluation on peak detection and gap-filling algorithms. The data set was created from a previous real-world study, of which a subset was used to extract and manually classify ion chromatograms by three mass spectrometry experts. The data set consists of the converted mass spectrometry files, intermediate processing files and the central file containing a table with all important information for the classified peaks. PMID: 32331455 [PubMed - as supplied by publisher]

metabolomics; +33 new citations

Sat, 25/04/2020 - 15:09
33 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 2020/04/25PubMed 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; +33 new citations

Sat, 25/04/2020 - 12:09
33 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 2020/04/25PubMed 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.

Integrated metabolomics and network pharmacology strategy for ascertaining the quality marker of flavonoids for Sophora flavescens.

Fri, 24/04/2020 - 15:00
Integrated metabolomics and network pharmacology strategy for ascertaining the quality marker of flavonoids for Sophora flavescens. J Pharm Biomed Anal. 2020 Apr 08;186:113297 Authors: Chen L, Huang X, Wang H, Shao J, Luo Y, Zhao K, Liu Y, Wang S Abstract Traditional Chinese medicines (TCMs) have been widely used in Asian countries for thousands of years due to their supreme quality and good clinical efficacy. However, the increasing demand for TCMs in recent decades warrants effective quality control methodology to avoid clinical problems. Therefore, comprehensive quality evaluation systems should be established for ensuring TCM's quality, in terms of chemical components, as well as bioactivity for identifying quality markers in TCM and developing suitable analytical methods for quality control. In this study, we selected Sophora flavescens (S. flavescens) as the research object and developed a novel integrated strategy combining metabolomics and network pharmacology to explore the quality markers. Firstly, we determined the targeted metabolomic profiles of seventy-four batches of S. flavescens (aged from 1 to 6 years) by UHPLC/QE-MS. Six potential markers were successfully screened, quantified and reverse-verified as the most influential effective compounds by UHPLC/QE-MS and multivariate statistical analysis. Secondly, the network of "components-targets-pathways" was constructed, and the pharmacological activities of six potential markers were predicted. Finally, we determined the anti-tumor activity of six flavonoids (kurarinone, norkurarinone, kuraridin, kushenol N, trifolirhizin, and genistein) as the quality markers for Sophora flavescens, evaluated their pharmacokinetic profiles and reviewed their existing pharmacological researches. Thus, integrated metabolomics and network pharmacology technology were applied for the effective discovery of quality markers of Chinese material medica. PMID: 32325403 [PubMed - as supplied by publisher]

Physiological stress response of the scleractinian coral Stylophora pistillata exposed to polyethylene microplastics.

Fri, 24/04/2020 - 15:00
Physiological stress response of the scleractinian coral Stylophora pistillata exposed to polyethylene microplastics. Environ Pollut. 2020 Apr 12;263(Pt A):114559 Authors: Lanctôt CM, Bednarz VN, Melvin S, Jacob H, Oberhaensli F, Swarzenski PW, Ferrier-Pagès C, Carroll AR, Metian M Abstract We investigated physiological responses including calcification, photosynthesis and alterations to polar metabolites, in the scleractinian coral Stylophora pistillata exposed to different concentrations of polyethylene microplastics. Results showed that at high plastic concentrations (50 particles/mL nominal concentration) the photosynthetic efficiency of photosystem II in the coral symbiont was affected after 4 weeks of exposure. Both moderate and high (5 and 50 particles/mL nominal) concentrations of microplastics caused subtle but significant alterations to metabolite profiles of coral, as determined by Nuclear Magnetic Resonance (NMR) spectroscopy. Specifically, exposed corals were found to have increased levels of phosphorylated sugars and pyrimidine nucleobases that make up nucleotides, scyllo-inositol and a region containing overlapping proline and glutamate signals, compared to control animals. Together with the photo-physiological stress response observed and previously published literature, these findings support the hypothesis that microplastics disrupt host-symbiont signaling and that corals respond to this interference by increasing signaling and chemical support to the symbiotic zooxanthellae algae. These findings are also consistent with increased mucus production in corals exposed to microplastics described in previous studies. Considering the importance of coral reefs to marine ecosystems and their sensitivity to anthropogenic stressors, more research is needed to elucidate coral response mechanisms to microplastics under realistic exposure conditions. PMID: 32325355 [PubMed - as supplied by publisher]

Hepatotoxicity study of combined exposure of DEHP and ethanol: A comprehensive analysis of transcriptomics and metabolomics.

Fri, 24/04/2020 - 15:00
Hepatotoxicity study of combined exposure of DEHP and ethanol: A comprehensive analysis of transcriptomics and metabolomics. Food Chem Toxicol. 2020 Apr 20;:111370 Authors: Li Y, Zhang Q, Fang J, Ma N, Geng X, Xu M, Yang H, Jia X Abstract Both di(2-ethylhexyl)phthalate (DEHP) and ethanol have toxic effects on the liver, and the oral exposure to DEHP in combination with ethanol may exist in the alcohol consumers, however, current food safety risk assessments based solely on the toxicity data of DEHP may underestimate the health impacts of phthalates, especially in population that continually consume alcoholic beverages. Here we performed a comprehensive analysis of transcriptomics and metabolomics to study if there is a synergistic effect of DEHP and ethanol on the liver of mice. We found that the expression of genes associated with lipid accumulation and oxidation elevated simultaneously when exposed to DEHP alone or combined with ethanol, based on the results of pathophysiological tests, we considered that the elevated level of lipid accumulation was more significant which caused hepatic lipid accumulation ultimately. We observed no difference in the transcriptome profiles between combined exposure group and DEHP group, but metabolites pathway enrichment analysis showed that ethanol and DEHP may have a synergistic effect on the unsaturated fatty acid metabolism. In summary, our results suggest that DEHP exposed alone or combined with ethanol caused hepatic lipid accumulation, ethanol and DEHP may have a synergistic effect on the unsaturated fatty acid metabolism. PMID: 32325186 [PubMed - as supplied by publisher]

Untargeted Metabolomics to Reveal Red Versus White Meat-Associated Gut Metabolites in a Prudent and Western Dietary Context.

Fri, 24/04/2020 - 15:00
Untargeted Metabolomics to Reveal Red Versus White Meat-Associated Gut Metabolites in a Prudent and Western Dietary Context. Mol Nutr Food Res. 2020 Apr 23;:e2000070 Authors: Goethals S, Rombouts C, Hemeryck LY, Van Meulebroek L, Van Hecke T, Vossen E, Van Camp J, De Smet S, Vanhaecke L Abstract SCOPE: To improve understanding of the epidemiological link between red and processed meat consumption and chronic diseases, more insight in the formation of metabolites during meat digestion is warranted. METHODS AND RESULTS: Untargeted MS-based metabolomics was applied to explore the impact of red and processed meat consumption (compared to chicken), combined with a prudent or Western dietary pattern. A pig feeding study (n = 32), as a sentinel for humans, was conducted in a 2 × 2 factorial design for four weeks. The luminal content of the small intestine and colon of the pigs were collected to determine their metabolic fingerprints. Seventy-six unique metabolites (38 in small intestine, 32 in colon, and 6 in both intestinal compartments) contributing to the distinct gut metabolic profiles of pigs fed either chicken or red and processed meat were (tentatively) identified. Consumption of red and processed meat resulted in higher levels of short- and medium-chain acylcarnitines and 3-dehydroxycarnitine, irrespective of dietary context, whereas long-chain acylcarnitines and monoacylglycerols were specifically associated with the red and processed-Western diet. CONCLUSION: The identification of red and processed meat-associated gut metabolites in this study contributes to the understanding of meat digestion in a complex but controlled dietary context and its potential health effects. This article is protected by copyright. All rights reserved. PMID: 32324972 [PubMed - as supplied by publisher]

NOREVA: enhanced normalization and evaluation of time-course and multi-class metabolomic data.

Fri, 24/04/2020 - 15:00
NOREVA: enhanced normalization and evaluation of time-course and multi-class metabolomic data. Nucleic Acids Res. 2020 Apr 23;: Authors: Yang Q, Wang Y, Zhang Y, Li F, Xia W, Zhou Y, Qiu Y, Li H, Zhu F Abstract Biological processes (like microbial growth & physiological response) are usually dynamic and require the monitoring of metabolic variation at different time-points. Moreover, there is clear shift from case-control (N=2) study to multi-class (N>2) problem in current metabolomics, which is crucial for revealing the mechanisms underlying certain physiological process, disease metastasis, etc. These time-course and multi-class metabolomics have attracted great attention, and data normalization is essential for removing unwanted biological/experimental variations in these studies. However, no tool (including NOREVA 1.0 focusing only on case-control studies) is available for effectively assessing the performance of normalization method on time-course/multi-class metabolomic data. Thus, NOREVA was updated to version 2.0 by (i) realizing normalization and evaluation of both time-course and multi-class metabolomic data, (ii) integrating 144 normalization methods of a recently proposed combination strategy and (iii) identifying the well-performing methods by comprehensively assessing the largest set of normalizations (168 in total, significantly larger than those 24 in NOREVA 1.0). The significance of this update was extensively validated by case studies on benchmark datasets. All in all, NOREVA 2.0 is distinguished for its capability in identifying well-performing normalization method(s) for time-course and multi-class metabolomics, which makes it an indispensable complement to other available tools. NOREVA can be accessed at https://idrblab.org/noreva/. PMID: 32324219 [PubMed - as supplied by publisher]

Inhibition of transcription by dactinomycin reveals a new characteristic of immunogenic cell stress.

Fri, 24/04/2020 - 15:00
Inhibition of transcription by dactinomycin reveals a new characteristic of immunogenic cell stress. EMBO Mol Med. 2020 Apr 23;:e11622 Authors: Humeau J, Sauvat A, Cerrato G, Xie W, Loos F, Iannantuoni F, Bezu L, Lévesque S, Paillet J, Pol J, Leduc M, Zitvogel L, de Thé H, Kepp O, Kroemer G Abstract Chemotherapy still constitutes the standard of care for the treatment of most neoplastic diseases. Certain chemotherapeutics from the oncological armamentarium are able to trigger pre-mortem stress signals that lead to immunogenic cell death (ICD), thus inducing an antitumor immune response and mediating long-term tumor growth reduction. Here, we used an established model, built on artificial intelligence to identify, among a library of 50,000 compounds, anticancer agents that, based on their molecular descriptors, were predicted to induce ICD. This algorithm led us to the identification of dactinomycin (DACT, best known as actinomycin D), a highly potent cytotoxicant and ICD inducer that mediates immune-dependent anticancer effects in vivo. Since DACT is commonly used as an inhibitor of DNA to RNA transcription, we investigated whether other experimentally established or algorithm-selected, clinically employed ICD inducers would share this characteristic. As a common leitmotif, a panel of pharmacological ICD stimulators inhibited transcription and secondarily translation. These results establish the inhibition of RNA synthesis as an initial event for ICD induction. PMID: 32323922 [PubMed - as supplied by publisher]

STAT3-dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer.

Fri, 24/04/2020 - 15:00
STAT3-dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer. Mol Syst Biol. 2020 Apr;16(4):e9247 Authors: Oberhuber M, Pecoraro M, Rusz M, Oberhuber G, Wieselberg M, Haslinger P, Gurnhofer E, Schlederer M, Limberger T, Lagger S, Pencik J, Kodajova P, Högler S, Stockmaier G, Grund-Gröschke S, Aberger F, Bolis M, Theurillat JP, Wiebringhaus R, Weiss T, Haitel A, Brehme M, Wadsak W, Griss J, Mohr T, Hofer A, Jäger A, Pollheimer J, Egger G, Koellensperger G, Mann M, Hantusch B, Kenner L Abstract Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential biomarkers for risk stratification, by utilizing a gene co-expression network of transcriptomics data in addition to laser-microdissected proteomics from human and murine prostate FFPE samples. We show up-regulation of oxidative phosphorylation (OXPHOS) in PCa on the transcriptomic level and up-regulation of the TCA cycle/OXPHOS on the proteomic level, which is inversely correlated to STAT3 expression. We hereby identify gene expression of pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging, and PSA level. Therefore, low PDK4 is a promising marker for PCa with dismal prognosis. PMID: 32323921 [PubMed - in process]

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