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Severe aconite poisoning successfully treated with veno-arterial extracorporeal membrane oxygenation:A case report

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World Journal of Clinical Cases 2024年第2期12卷 399-404页

作者： Saeko Kohara Yoshito Kamijo Ryoko Kyan Ichiro Okada Eiju Hasegawa Soichiro Yamada Koichi Imai Asuka Kaizaki-Mitsumoto Satoshi Numazawa Department of Critical Care Medicine and Trauma National Hospital Organization Disaster Medical CenterTokyo 1900014Japan Department of Clinical toxicology Saitama Medical UniversitySaitama 3500495Japan Saitama Prefectural Institute of Public Health Saitama Prefectural Institute of Public HealthSaitama 3550133Japan division of toxicology Department of PharmacologyToxicology and TherapeuticsShowa University School of PharmacyTokyo 1428555Japan

BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular *** describe a case of severe aconite poisoning that was successfully treated through venoarterial extracorporeal membrane oxygenation(VA-ECMO)and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).CASE SUMMARY A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled,“Aconitum japonicum Thunb”.Two hours after arrival,VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and *** hours after arrival,an electrocardiogram revealed a return to sinus *** patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5,*** hospital day 15,he was transferred to a psychiatric *** other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS,revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the *** on admission contained 1.50 ng/mL of *** hospital day 2,neither were *** on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine,but these rapidly decreased after hospital day *** The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.

关键词： Aconite poisoning Fatal arrhythmia Veno-arterial extracorporeal membrane oxygenation Aconitine Mesaconitine Case report

Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

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Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： Helen M.Knight Merve Demirbugen ?z Adriana PerezGrovas-Saltijeral division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham Department of Pharmaceutical toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer’s disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer’s disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is en

关键词： 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

Residential energy transition and chronic respiratory diseases

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The Innovation 2024年第3期5卷 33-43页

作者： Hongcheng Wei Qiurun Yu Danrong Chen Mingzhi Zhang Quanquan Guan Bo Hang Antoine M.Snijders Adrian Covaci Yankai Xia State Key Laboratory of Reproductive Medicine and Offspring Health Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China Key Laboratory of Modern toxicology of Ministry of Education School of Public HealthNanjing Medical UniversityNanjing 211166China The Affiliated Wuxi People’s Hospital of Nanjing medical University Wuxi People’s HospitalWuxi Medical CenterNanjing Medical UniversityWuxi 214023China Biological Systems and Engineering division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Toxicological Centre University of Antwerp2610 WilrijkBelgium

Obtaining clean energy is of prime importance for planetary health and sustainable *** aimed to assess the association between residential energy transition and the risk of chronic respiratory *** data from the Global Health Observatory and Global Burden of Diseases,Injuries,and Risk Factors Study,we delineated the spatial distribution and temporal trends of the population using clean fuels for cooking at a global *** the China Health and Retirement Longitudinal Study,we performed rigorous and well-structured multistage analyses incorporating both cross-sectional and prospective data analyses to examine the associations between solid fuel use,residential energy transition,duration of solid fuel use,and the risk of chronic respiratory *** great progress,huge disparities in access to clean energy persist *** energy transition was associated with a lower risk of chronic respiratory *** the period of 2011–2013,compared with persistent solid fuel users,both participants who switched from solid to clean fuels(adjusted risk ratio[RR]0.78,95%confidence interval[CI]0.62–0.98)and persistent clean fuel users(adjusted RR 0.71,95%CI 0.57–0.89)had significantly lower risk of chronic respiratory diseases(p<0.001 for trend).Consistent associations were observed in the period of 2011–2015 and 2011–*** energy transition from solid to clean fuels could reduce the risk of chronic respiratory *** is a valuable lesson for policy-makers and the general public to accelerate energy switching to alleviate the burden of chronic respiratory diseases and achieve health benefits,particularly in low-and middle-income countries.

关键词： cooking income globally

Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension

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Chronic Diseases and Translational Medicine 2024年第2期10卷 102-117页

作者： Nicholas R.Powell Tyler Shugg Jacob Leighty Matthew Martin Rolf P.Kreutz Michael T.Eadon Dongbing Lai Tao Lu Todd C.Skaar division of Clinical Pharmacology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Pharmacology and toxicology School of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Cardiology School of MedicineKrannert Institute of CardiologyIndiana UniversityIndianapolisIndianaUSA division of Nephrology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Department of medical and Molecular Genetics School of MedicineIndiana UniversityIndianapolisIndianaUSA

Background Hypertension(HTN)involves genetic variability in the renin-angiotensin system and influences antihypertensive *** previously reported that angiotensinogen(AGT)messenger RNA(mRNA)is endogenously bound by miR-122-5p and rs699 A>G decreases reporter mRNA in the microRNA functional-assay *** AGT promoter variant rs5051 C>T is in linkage disequilibrium(LD)with rs699 A>G and increases AGT *** independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C>T counterbalances AGT decreased by rs699 A>G,and when these variants occur independently,it translates to HTN-related *** We used in silico,in vitro,in vivo,and retrospective models to test this *** In silico,rs699 A>G is predicted to increase miR-122-5p binding affinity by 3%.Mir-eCLIP results show rs699 is 40–45 nucleotides from the strongest microRNA-binding site in the AGT ***,rs699 A>G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression ***-Tissue Expression(GTEx)and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A>G occurs independently from rs5051 C>***,GTEx and the in vitro experiments suggest rs699 A>G confers cell-type-specific effects on AGT mRNA abundance,and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A>G associations with *** We found that rs5051 C>T and rs699 A>G significantly associate with systolic blood pressure in Black participants in the UK Biobank,demonstrating a fourfold larger effect than in White *** studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C>T or rs699 A>*** like this will help clinicians move beyond the use of race as a surrogate for genotype.

关键词： angiotensinogen genetic and genomic medicine hypertension rs699

High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and Medicine TIGEMPozzuoliNaples 80131Italy medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

Elucidating regulatory processes of intense physical activity by multi-omics analysis

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Military medical Research 2024年第4期11卷 479-499页

作者： Ernesto S.Nakayasu Marina A.Gritsenko Young-Mo Kim Jennifer E.Kyle Kelly G.Stratton Carrie D.Nicora Nathalie Munoz Kathleen M.Navarro Daniel Claborne Yuqian Gao Karl K.Weitz Vanessa L.Paurus Kent J.Bloodsworth Kelsey A.Allen Lisa M.Bramer Fernando Montes Kathleen A.Clark Grant Tietje Justin Teeguarden Kristin E.Burnum-Johnson Biological Sciences division Pacific Northwest National LaboratoryRichlandWA 99352USA Environmental and Molecular Sciences division Pacific Northwest National LaboratoryRichlandWA 99352USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthWestern States DivisionDenverCO 80204USA Computational Analytics division Pacific Northwest National LaboratoryRichlandWA 99352USA National Security Directorate Pacific Northwest National LaboratoryRichlandWA 99352USA Los Angeles County Fire Department Los AngelesCA 90063USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthRespiratory Health DivisionMorgantownWV 26505USA Environmental and Molecular toxicology Oregon State UniversityCorvallisOR 97331USA

Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work ***:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise *** profiles ***-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics ***:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of *** blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy *** urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid *** saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory ***:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

关键词： Multi-omics analysis Intense exercise Human performance Biofluids Metabolism Immunity

HDPairFinder:A data processing platform for hydrogen/deuterium isotopic labeling-based nontargeted analysis of trace-level amino-containing chemicals in environmental water

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Journal of Environmental Sciences 2024年第2期136卷 583-593页

作者： Tingting Zhao Kristin Carroll Caley B.Craven Nicholas J.P.Wawryk Shipei Xing Jian Guo Xing-Fang Li Tao Huan Department of Chemistry Faculty of ScienceUniversity of British ColumbiaVancouver Campus2036 Main MallVancouverBritish ColumbiaV6T 1Z1Canada division of Analytical and Environmental toxicology Department of Laboratory Medicine and PathologyFaculty of Medicine and DentistryUniversity of AlbertaEdmontonAlberta T6G 2G3Canada

The combination of hydrogen/deuterium(H/D)formaldehyde-based isotopic methyl labeling with solid-phase extraction and high-performance liquid chromatography–high resolution mass spectrometry(HPLC-HRMS)is a powerful analytical solution for nontargeted analysis of trace-level amino-containing chemicals in water *** the huge amount of chemical information generated in HPLC-HRMS analysis,identifying all possible H/Dlabeled amino chemicals presents a significant challenge in data *** address this,we designed a streamlined data processing pipeline that can automatically extract H/D-labeled amino chemicals from the raw HPLC-HRMS data with high accuracy and ***,we developed a cross-correlation algorithm to correct the retention time shift resulting from deuterium isotopic effects,which enables reliable pairing of H-and D-labeled ***,we implemented several bioinformatic solutions to remove false chemical features generated by in-source fragmentation,salt adduction,and natural13C ***,we used a data mining strategy to construct the AMINES library that consists of over 38,000 structure-disjointed primary and secondary amines to facilitate putative compound ***,we integrated these modules into a freely available R program,*** rationale of each module was justified and its performance tested using experimental H/D-labeled chemical standards and authentic water *** further demonstrated the application of HDPairFinder to effectively extract N-containing contaminants,thus enabling the monitoring of changes of primary and secondary N-compounds in authentic water *** is a reliable bioinformatic tool for rapid processing of H/D isotopic methyl labeling-based nontargeted analysis of water samples,and will facilitate a better understanding of N-containing chemical compounds in water.

关键词： Isotope labeling Nontargeted analysis Reactive N-compounds HPLC-HRMS Source water

A Comprehensive Review on Preclinical Safety and Toxicity of Medicinal Plants

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Clinical Complementary Medicine and Pharmacology 2024年第1期4卷 95-111页

作者： Madhav Nilakanth Mugale Kapil Dev Bhumika S.More Vaishali Sunil Mishra Kaveri R.Washimkar Kishan Singh Rakesh Maurya Srikanta Kumar Rath Debprasad Chattopadhyay Naibedya Chattopadhyay division of toxicology and Experimental Medicine CSIR-Central Drug Research Institute(CSIR-CDRI)Lucknow 226031India division of Phytochemistry CSIR-Central Institute of Medicinal and Aromatic Plants(CSIR-CIMAP)Lucknow 226015India Medicinal and Process Chemistry division CSIR-CDRI Lucknow 226031India division of Endocrinology CSIR-CDRI Lucknow 226031India division of Ethnomedicine ICMR-National Institute of Traditional MedicineNehru NagarBelagavi 590010and ICMR-Virus UnitKolkata 700010India Department of Health Research NSHM Knowledge CampusKolkata 700051India

Background:Globally,80%people use plant-derived products for treating or preventing *** prevalent perception about medicinal plants is that they are safe and devoid of adverse ***,approximately 1,50,000 plants contain toxic ***:The present review focuses on medicinal plant extracts/fractions toxicity assessments made in preclin-ical models by oral ***:Detail studies were searched from databases including PubMed and Google Scholar.A manual reference screening of the selected studies was done to identify relevant articles,with no language restriction being imposed at the time of ***:The studies included were performed in rodents,and the test substances were administered *** search revealed 33 widely used plants or products with significant toxicity,and phytochemicals from these plants have been *** a systematic review,we identified a plethora of medicinal plant extracts reporting safety and toxicity ***:In the future,preclinical toxicokinetic studies of herbs and the determination of their no-observed-adverse-effect levels are required for a complete safety ***,the interaction of herbs with com-monly used/over-the-counter drugs in terms of the latter’s metabolic profile should be undertaken.

关键词： Extract Herbal medicine Toxicity Rodent Secondary metabolite

Gastric acid inhibitory and gastric protective effects of cannabis and cannabinoids

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Asian Pacific Journal of Tropical Medicine 2016年第5期9卷 401-408页

作者： Omar Abdel-Salam Department of toxicology and Narcotics Medical Division National Research Centre

Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation, the role of this ‘endocannabinoid system’ in different pathophysiologic processes is beginning to be delineated. There is evidence that CB1 receptor stimulation with synthetic cannabinoids or Cannabis sativa extracts rich in ?9-tetrahydrocannabinol inhibit gastric acid secretion in humans and in experimental animals. This is specially seen when gastric acid secretion is stimulated by pentagastrin, carbachol or 2 deoxy-D-glucose. Cannabis and/or cannabinoids protect the gastric mucosa against noxious challenge with non-steroidal anti-inflammatory drugs, ethanol as well as against stress induced mucosal damage. Cannabis/cannabinoids might protect the gastric mucosa by virtue of its antisecretory, antioxidant, anti-inflammatory, and vasodilator properties.

关键词： Cannabis sativa Gastric mucosa Gastric acid