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Biological Evaluation of Lysionotin:a Novel Inhibitor of 5-Lipoxygenase for Anti-glioma

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Chinese Journal of Integrative medicine 2024年第9期30卷 826-834页

作者： SHAO Xin-xin CHEN Cong LIU Jie LI Qing-jun HE Shan QI Xiang-hua FU Xian-jun WANG Zhen-guo The First Clinical College of medicine Shandong University of Traditional Chinese MedicineJinan250355China Institute for Literature and Culture of Chinese medicine Shandong University of Traditional Chinese MedicineJinan250355China Key Laboratory of Classical Theory of Traditional Chinese medicine Ministry of EducationShandong University of Traditional Chinese MedicineJinan250355China College of Pharmacy Shandong University of Traditional Chinese MedicineJinan250355China Experimental Center Shandong University of Traditional Chinese MedicineJinan250355China Neurology Department Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan250014China Marine Traditional Chinese medicine Research Center Qingdao Academy of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineQingdao266114Shandong ProvinceChina

Objective:To explore the potential mechanism of lysionotin in treating ***:First,target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of *** binding between 5-lipoxygenase(5-LO)and lysionotin was detected by surface plasmon resonance(SPR)and molecular docking,and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis,***,the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry(LC-MS/MS).The protein expression,intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot,flow cytometry and fluorescence labeling,***:Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO,a key enzyme involved in the arachidonic acid metabolism pathway,to inhibit the proliferation of *** docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds,forming bonds with His600,Gln557,Asn554,and *** analysis further confirmed the interaction between 5-LO and ***,enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50%inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58µmol/L,respectively,and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid(P<0.05),and moreover,the LC-MS/MS results indicated that lysionotin can enter glioma cells well(P<0.01)and inhibit their *** blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO(P<0.05)and downstream leukotriene B4 receptor(P<0.01).In addition,the results showed that lysionotin affected intracellular calcium ion concentration by inh

关键词： 5-lipoxygenase inhibitor lysionotin 5-lipoxygenase leukotriene B4 calcium ion cytoskeleton

Epidemiological and Diagnostic Profile of Patients with Chronic Hepatitis B Virus from 2017 to 2021 in Parakou, Republic of Benin

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Advances in Infectious Diseases 2024年第1期14卷 147-161页

作者： Khadidjatou Saké Cossi Angelo Attinsounon Aboudou Raϊmi Kpossou Morayo Omm Ani Salami Astrid Alexandrine Hountondji Kofi-Mensa Savi de Tovè Rhonel Ahanhanzo-Glèlè Kpémahoun René Kèkè Sossa Edmond Gbédo Jean Sehonou Nicolas Kodjoh Department of medicine and Medical Specialties Faculty of Medicine University of Parakou Parakou Benin Department of medicine and Medical Specialties Faculty of Health Sciences University of Abomey-Calavi Cotonou Benin Health program to Fight AIDS Cotonou Benin National program for the Control of Hepatitis Cotonou Benin

Introduction: Viral hepatitis B is a public health problem worldwide. The objective of this study was to determine the epidemiological and diagnostic profile of chronic carriers of hepatitis B virus seen for gastroenterology consultations in Parakou, Republic of Benin. Patients and Methods: This was a cross-sectional and descriptive study with retrospective data collection. Patients seen for gastroenterology consultations from January 1, 2017 to June 30, 2021 at the Regional Teaching Hospital of Borgou/Alibori (CHUD-B/A) and having been diagnosed as chronic carriers of hepatitis B virus were included. A minimum initial assessment was required to be included. The minimum sample size was calculated with Schwartz formula. The variable of interest was the detection of HBsAg twice and at least 6 months apart. The other variables studied were sociodemographic, clinical and paraclinical data. The data collected were analyzed using SPSS 17 software. Results: A total of 2786 patients were seen for gastroenterology consultations, including 1126 (40.4%) HBsAg-positive patients. Among them, 417 patients met the inclusion criteria and were the subject of the present study. The average age of the patients was 34.8 ± 10.5 years. Two hundred and forty-seven patients (65.7%) were male, representing a sex ratio of 1.9. The discovery of positive HBsAg status was made during systematic screening in 231 patients (55.4%). Scarifications were noted in 373 patients (89.4%). Asthenia was reported in 184 patients (44.1%). Co-infections with human immunodeficiency virus, hepatitis C and D viruses were 0% (0 in 92), 2.8% (4 in 146) and 14.3% (2 in 146), respectively. During the initial assessment, 274 patients (65.7%) were sero-negative for chronic HBeAg infection, 21 (5%) had clinically significant fibrosis including 16 (3.8%) at the stage of cirrhosis and 7 patients (5.4%) had hepatocellular carcinoma. Conclusion: In Parakou, chronic hepatitis B virus infection is common and affects young pe

关键词： Chronic Infection HBV Epidemiology Diagnosis Parakou

Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes

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World Journal of Diabetes 2024年第6期15卷 1263-1271页

作者： Xiang-Yu Gao Chen-Xia Zhou Hong-Mei Li Min Cheng Da Chen Zi-Yi Li Bo Feng Jun Song Department of Endocrinology East HospitalTongji University School of MedicineShanghai 200120China Department of Endocrinology Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdao 266000Shandong ProvinceChina Department of Immunization program Huangdao District Center for Disease Prevention and ControlQingdao 266400Shandong ProvinceChina

BACKGROUND Cognitive dysfunction is the main manifestation of central *** cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive *** is closely related to neurological abnormalities,while often disregarded in clinical *** in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)*** A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East *** participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(<7.875%),Q2(7.875%-9.050%),Q3(9.050%-11.200%)and Q4(≥11.200%).Clinical data were collected and measured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical ***,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance *** The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).Spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(P<0.05),whereas HOMA-βwas negatively correlated with the HbA1c level(P<0.05).Ordered multiple logistic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-

关键词： Type 2 diabetes mellitus Hemoglobin A1c Proton magnetic resonance spectroscopy Neurotransmitters Central neuropathy

Molecular characterization and structure basis of a malonyltransferase with both substrate promiscuity and catalytic regiospecificity from Cistanche tubulosa

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2333-2348页

作者： Xiao Liu Yuyu Liu Xiping Xu Wenqian Huang Yaru Yan Yingxia Wang Weisheng Tian Ting Mo Xiaoxue Cui Jun Li She-Po Shi Pengfei Tu Modern Research Center for Traditional Chinese medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China Modern Research Center for Traditional Chinese medicine School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100029China

Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides ***,the catalytic potential and structural basis of plant malonyltransferase are far from being fully *** work identified a new malonyltransferase CtMaT1 from Cistanche *** displayed unprecedented mono-and/or di-malonylation activity toward diverse glucosides with different aglycons.A“one-pot”system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated *** investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse ***,it recognizes malonyl-CoA through strong electrotactic and hydrogen ***/MM calculation revealed the H167-mediated SN2 reaction mechanism of CtMaT1,while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167,resulting in its high malonylation *** energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates,emphasizing CtMaT1's preference for ***,a mutant CtMaT1H36A with notably increased di-malonylation activity was *** underlying molecular mechanism was illuminated through MM/GBSA binding free energy *** study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives,while also providing a versatile tool for enzymatic malonylation applications in pharmacology.

关键词： Plant acyltransferase Malonyltransferase Malonylated glycosides Enzymatic catalysis Enzyme promiscuity

Extracellular vesicles as tools and targets in therapy for diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 872-912页

作者： Mudasir A.Kumar Sadaf K.Baba Hana Q.Sadida Sara Al.Marzooqi Jayakumar Jerobin Faisal H.Altemani Naseh Algehainy Mohammad A.Alanazi Abdul-Badi Abou-Samra Rakesh Kumar Ammira S.Al-Shabeeb Akil Muzafar A.Macha Rashid Mir Ajaz A.Bhat Watson-Crick Centre for Molecular medicine Islamic University of Science and TechnologyAwantiporaKashmir 192122India Department of Human Genetics-Precision medicine in Diabetes Obesity and Cancer ProgramSidra MedicineDohaQatar Qatar Metabolic Institute Academic Health SystemHamad Medical CorporationDohaQatar Department of Medical Laboratory Technology Prince Fahad Bin Sultan Chair for Biomedical ResearchFaculty of Applied Medical SciencesUniversity of TabukTabukSaudi Arabia School of Biotechnology Shri Mata Vaishno Devi UniversityKatraIndia

Extracellular vesicles(EVs)are nano-sized,membranous structures secreted into the extracellular *** exhibit diverse sizes,contents,and surface markers and are ubiquitously released from cells under normal and pathological *** serum is a rich source of these EVs,though their isolation from serum proteins and non-EV lipid particles poses *** vesicles transport various cellular components such as proteins,mRNAs,miRNAs,DNA,and lipids across distances,influencing numerous physiological and pathological events,including those within the tumor microenvironment(TME).Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents,drug delivery systems,and disease *** in cancer diagnostics,EV detection can pave the way for early identification and offers potential as diagnostic ***,various EV subtypes are emerging as targeted drug delivery tools,highlighting their potential clinical *** need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains *** into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the *** this review,we discuss in detail the roles of EVs across various conditions,including cancers(encompassing head and neck,lung,gastric,breast,and hepatocellular carcinoma),neurodegenerative disorders,diabetes,viral infections,autoimmune and renal diseases,emphasizing the potential advancements in molecular diagnostics and drug delivery.

关键词： diseases sized sizes

Oketani massage with jasmine oil improves breast milk production on postpartum days 1-3

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Journal of Integrative Nursing 2024年第1期6卷 35-40页

作者： Ni Made Ratih Comala DEWI Made Ririn Sri WULANDARI Yupin AUNGSUROCH Department of Nursing Bali Mandara HospitalBaliIndonesia Bachelor program of Nursing Faculty of MedicineUniversitas Pendidikan GaneshaBaliIndonesia Nursing Management Faculty of NursingChulalongkorn UniversityBangkokThailand

Objective:This study aimed to determine the effect of Oketani massage with jasmine oil on improving breast milk production on days *** and Methods:This preexperimental one-group pretest-posttest design was conducted with 44 eligible respondents,selected using an incidental sampling *** massage with jasmine oil was conducted once a day for 3 consecutive days.A total of 44 respondents were selected with incidental *** breast milk production was observed through the frequency of baby urination in 24 h,the frequency of baby defecation in 24 h,the baby’s weight,and the length of time the baby slept or remained calm after ***:Results showed that Oketani massage using jasmine oil impacted on increasing breast milk production in postpartum on days 1-3(Z=6.633,P=0.000).The baby’s weight in 3 days was increased after intervention compared with intervention before(2858.25±180.62 g vs.2881.66±180.96 g,t=55.33,P=0.000),the baby’s urination frequency was increased after intervention(4.55±0.50 vs.7.20±0.70,t=17.87,P=0.000),the breastfeeding frequency has decreased(10.27±1.42 vs.8.82±0.82,t=6.94,P=0.000),and the time of baby’s sleeping or calming state has increased(5.14±6.46 h vs.8.48±10.24 h,t=2.11,P=0.041).Conclusion:Oketani massage combined with jasmine oil has been shown to be effective on improving breast milk production on days 1-3.

关键词： Exclusive breastfeeding Oketani massage postpartum

The potential of herbal drugs to treat heart failure:The roles of Sirt1/AMPK

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Journal of Pharmaceutical Analysis 2024年第2期14卷 157-176页

作者： Tao Zhang Lei Xu Xiaowei Guo Honglin Tao Yue Liu Xianfeng Liu Yi Zhang Xianli Meng State Key Laboratory of Southwestern Chinese medicine Resources Innovative Institute of Chinese Medicine and PharmacyChengdu University of Traditional Chinese MedicineChengdu611137China College of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu611137China School of Ethnic medicine Chengdu University of Traditional Chinese MedicineChengdu611137China Meishan Hospital of Chengdu University of Traditional Chinese medicine MeishanSichuan620032China

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic *** addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately *** information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,*** play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

关键词： Heart failure Silent information regulator 1 Adenosine monophosphate-activated protein kinase Traditional Chinese medicine

Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples

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Journal of Pharmaceutical Analysis 2024年第5期14卷 733-743页

作者： Alongkorn Kurilung Suphitcha Limjiasahapong Khwanta Kaewnarin Pattipong Wisanpitayakorn Narumol Jariyasopit Kwanjeera Wanichthanarak Sitanan Sartyoungkul Stephen Choong Chee Wong Nuankanya Sathirapongsasuti Chagriya Kitiyakara Yongyut Sirivatanauksorn Sakda Khoomrung Siriraj Center of Research Excellent in Metabolomics and Systems Biology(SiCORE-MSB) Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok10700Thailand Siriraj Metabolomics and Phenomics Center Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok10700Thailand Department of Biomedical Informatics University of Arkansas for Medical SciencesLittle RockAR72205USA SingHealth Duke-NUS Institute of Biodiversity medicine National Cancer Centre Singapore168583Singapore Waters Pacific Pte. Ltd.Singapore117528Singapore program in Translational medicine Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok10400Thailand Chakri Naruebodindra Medical Institute Faculty of Medicine Ramathibodi HospitalMahidol UniversitySamut Prakan10540Thailand Department of medicine Ramathibodi HospitalMahidol UniversityBangkok10400Thailand Department of Biochemistry Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok10700Thailand Center of Excellence for Innovation in Chemistry(PERCH-CIC) Faculty of ScienceMahidol UniversityBangkok10400Thailand

The collision cross-sections(CCS)measurement using ion mobility spectrometry(IMS)in combination with mass spectrometry(MS)offers a great opportunity to increase confidence in metabolite ***,owing to the lack of sensitivity and resolution,IMS has an analytical challenge in studying the CCS values of very low-molecular-weight metabolites(VLMs250 Da).Here,we describe an analytical method using ultrahigh-performance liquid chromatography(UPLC)coupled to a traveling wave ion mobility-quadrupole-time-of-flight mass spectrometer optimized for the measurement of VLMs in human urine *** experimental CCS values,along with mass spectral properties,were reported for the 174 *** experimental data included the mass-to-charge ratio(m/z),retention time(RT),tandem MS(MS/MS)spectra,and CCS *** the studied metabolites,263 traveling wave ion mobility spectrometry(TWIMS)-derived CCS values(TWCCSN2)were reported for the first time,and more than 70%of these were CCS values of *** TWCCSN2 values were highly repeatable,with inter-day variations of<1%relative standard deviation(RSD).The developed method revealed excellent TWCCSN2 accuracy with a CCS difference(DCCS)within±2%of the reported drift tube IMS(DTIMS)and TWIMS CCS *** complexity of the urine matrix did not affect the precision of the method,as evidenced by DCCS within±1.92%.According to the Metabolomics Standards Initiative,55 urinary metabolites were identified with a confidence level of *** these 55 metabolites,53(96%)were *** larger number of confirmed compounds found in this study was a result of the addition of TWCCSN2 values,which clearly increased metabolite identification confidence.

关键词： Very low-molecular-weight metabolites Traveling wave ion mobility Collision cross-section Human urine

Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model:A cohort study

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World Journal of Hepatology 2024年第2期16卷 193-210页

作者： Jonathan Soldera Leandro Luis Corso Matheus Machado Rech Vinícius Remus Ballotin Lucas Goldmann Bigarella Fernanda Tomé Nathalia Moraes Rafael Sartori Balbinot Santiago Rodriguez Ajacio Bandeira de Mello Brandão Bruno Hochhegger Post Graduate program at Acute medicine and Gastroenterology University of South WalesCardiff CF371DLUnited Kingdom Postgraduate program in Pathology Federal University of Health Sciences of Porto Alegre(UFCSPA)Porto Alegre 90050-170Brazil Department of Engineering Universidade de Caxias do SulCaxias do Sul 95070-560Brazil School of medicine Universidade de Caxias do SulCaxias do Sul 95070-560Brazil Postgraduate program in Hepatology Federal University of Health Sciences of Porto Alegre(UFCSPA)Porto Alegre 90050-170Brazil

BACKGROUND Liver transplant(LT)patients have become older and *** rate of post-LT major adverse cardiovascular events(MACE)has increased,and this in turn raises 30-d post-LT *** cardiac stress testing loses accuracy when applied to pre-LT cirrhotic *** To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional *** This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic *** developed a predictive model for post-LT MACE(defined as a composite outcome of stroke,new-onset heart failure,severe arrhythmia,and myocardial infarction)using the extreme gradient boosting(XGBoost)machine learning *** addressed missing data(below 20%)for relevant variables using the k-nearest neighbor imputation method,calculating the mean from the ten nearest neighbors for each *** modeling dataset included 83 features,encompassing patient and laboratory data,cirrhosis complications,and pre-LT cardiac *** performance was assessed using the area under the receiver operating characteristic curve(AUROC).We also employed Shapley additive explanations(SHAP)to interpret feature *** dataset was split into training(75%)and testing(25%)*** was evaluated using the Brier *** followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for ***-learn and SHAP in Python 3 were used for all *** supplementary material includes code for model development and a user-friendly online MACE prediction *** Of the 537 included patients,23(4.46%)developed in-hospital MACE,with a mean age at transplantation of 52.9 *** majority,66.1%,were *** XGBoost model achieved an impressive AUROC of 0.89 during the training *** model exhibited accuracy,precision,recall,and F1-score values of 0.84,0.85,0.80,and 0.79,***

关键词： Liver transplantation Major adverse cardiac events Machine learning Myocardial perfusion imaging Stress test