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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

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Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases

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Neural Regeneration Research 2024年第3期19卷 571-577页

作者： Sonia Irais Gonzalez-Cano Gonzalo Flores Jorge Guevara Julio Cesar Morales-Medina Samuel Treviño Alfonso Diaz faculty of Chemical Sciences Benemerita Autonomous University of PueblaPueblaMexico Institute of Physiology Benemerita Autonomous University of PueblaPueblaMexico department of biochemistry Faculty of MedicineNational Autonomous University of MexicoMexico CityMexico Animal Reproduction Research Center CINVESTAV-Autonomous University of TlaxcalaTlaxcalaMexico

Aging is a natural phenomenon characterized by a progressive decline in physiological integrity,leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases,including cardiovascular diseases,osteoporosis,cancer,diabetes,and *** is considered the major risk factor for Parkinson’s and Alzheimer’s disease ***,diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative ***,no treatment can effectively reverse these neurodegenerative ***,some antidiabetic drugs have opened the possibility of being used against neurodegenerative *** the previous framework,Vanadium species have demonstrated a notable antidiabetic *** research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic *** results suggest that these polyoxidovanadates induce neuronal and cognitive restoration *** review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain,constituting a therapeutic alternative for aging and neurodegenerative diseases.

关键词： Alzheimer’s disease antidiabetic brain cognition diabetes insulin neurodegeneration neuroinflammation oxidative stress Vanadium species

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Z-shaped incision without epithelial resection in pterygium surgery

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1262-1266页

作者： Satoru Kase Shinki Chin Susumu Ishida department of Ophthalmology Faculty of Medicine and Graduate School of MedicineHokkaido UniversitySapporo 060-8638Japan

AIM:To introduce a novel surgical technique using a Z-shaped incision without epithelial resection in ophthalmic ***:This was a prospective *** pterygium surgery,all proliferative tissues were separated from the cornea and conjunctiva without resection of the *** unaffected conjunctiva was incised in a *** upper(or lower)conjunctival flap was sutured to the lower(or upper)normal conjunctiva on the limbal sclera,while the proliferative tissue was sutured to the upper conjunctiva(or lower)near the ***:Ten patients with pterygia were eligible for this *** patients with primary pterygia and 2 with recurrent pterygia were *** age of patients at surgery ranged from 47 to 90y(average:71.9y).Five patients each showed right and left-sided *** postoperative follow-up periods were from 8 to 78mo(average:25.0mo).The surgery was successfully conducted and wounds were favorably reconstructed in all *** proliferative tissues sutured to the normal conjunctiva showed palor and attenuated neovessles,and never showed re-growth after *** patients did not show *** pterygium was noted in 1 patient,but additional treatments were not ***:The procedure involves the reconstruction of pterygial tissue and normal conjunctiva using a Z-shaped *** scleral limbal wound can be covered with nonaffected conjunctiva without any excision of conjunctival epithelia in patients with primary or recurrent pterygia.

关键词： pterygium surgery Z-shape non-resection

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Promising use of metformin in treating neurological disorders:biomarker-guided therapies

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Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： Allison Loan Charvi Syal Margarita Lui Ling He Jing Wang Regenerative medicine Program Ottawa Hospital Research InstituteOttawaONCanada department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada department of Pediatrics and medicine Johns Hopkins Medical SchoolBaltimoreMDUSA department of Cellular and Molecular medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of Ottawa Brain and Mind Research Institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available *** most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy ***,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological *** that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological *** molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted *** this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy

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Comparing 11 early warning scores and three shock indices in early sepsis prediction in the emergency department

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World Journal of Emergency medicine 2024年第4期15卷 273-282页

作者： Rex Pui Kin Lam Zonglin Dai Eric Ho Yin Lau Carrie Yuen Ting Ip Ho Ching Chan Lingyun Zhao Tat ChiTsang Matthew Sik Hon Tsui Timothy Hudson Rainer department of Emergency medicine School of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina School of Public Health Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina Accident and Emergency department Queen Mary HospitalHong KongChina

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED).METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong *** primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED *** c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time ***:We analyzed 601 patients,of whom 166(27.6%)developed ***2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary ***,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),*** discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time ***:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

关键词： Sepsis Emergency department Clinical prediction rule Early warning score Shock index

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Advances in clinical applications of bioceramics in the new regenerative medicine era

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World Journal of Clinical Cases 2024年第11期12卷 1863-1869页

作者： Noha Elshazly Fayza Eid Nasr Ayat Hamdy Safa Saied Mohamed Elshazly Tissue Engineering Laboratory Faculty of DentistryAlexandria UniversityAlexandria 21526Egypt department of biochemistry Faculty of ScienceAlexandria UniversityAlexandria 21526Egypt Public Dental Clinic Central Administration of DentistryMinistry of Health and PopulationAlexandria 21554Egypt department of Surgery Faculty of Veterinary MedicineAlexandria 21526Egypt

In this editorial,we comment on the hard and soft tissue applications of different ceramic-based scaffolds prepared by different mechanisms such as 3D printing,sol-gel,and *** new concept of regenerative medicine relies on biomaterials that can trigger in situ tissue regeneration and stem cell recruitment at the defect site.A large percentage of these biomaterials is ceramic-based as they provide the essential requirements of biomaterial principles such as tailored multisize porosity,antibacterial properties,and angiogenic *** these previously mentioned properties put bioceramics on top of the hierarchy of biomaterials utilized to stimulate tissue regeneration in soft and hard tissue *** clinical applications registered the use of these materials in triggering soft tissue regeneration in healthy and diabetic patients such as bioactive glass *** results were promising and opened new frontiers for utilizing these materials on a larger *** same results were mentioned when using different forms and formulas of bioceramics in hard defect *** bioceramics were used in combination with other polymers and biological scaffolds to improve their regenerative and mechanical *** this progress will enable a larger scale of patients to receive such services with ease and decrease the financial burden on the government.

关键词： Regenerative medicine Bioceramics Chronic wounds Bone defects Clinical applications

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The role of polymorphic cytochrome P450 gene(CYP2B6)in B-chronic lymphocytic leukemia(B-CLL)incidence and outcome among Egyptian patients

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Oncology Research 2024年第4期32卷 785-797页

作者： MENNA AL-ADL MAGDY MYOUSSEF AHMED EL-SEBAIE SHERIF REFAAT AFAF EL-SAID Division of biochemistry Department of ChemistryFaculty of ScienceMansoura UniversityMansoura35511Egypt Hematology Unit Department of Clinical PathologyFaculty of MedicineMansoura UniversityMansoura35511Egypt Medical Oncology Unit Oncology Center Mansoura UniversityMansoura35511Egypt department of Genetics Mansoura University Children’s HospitalMansoura35511Egypt

Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including *** gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used *** research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide *** was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy *** presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed *** CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT ***,OR=5.4,p<0.001)*** cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian *** variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

关键词： B-CLL Xenobiotics Cytochromes P450 CYP2B6

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Prognostic factors and clinical features of rhino-orbitalmucormycosis cases:an update for patient and visual survivals

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 916-923页

作者： Mustafa Aksoy Altan Atakan Ozcan Burak Ulas department of Ophthalmology Cukurova University Faculty of MedicineSaricamAdana 01330Türkiye

AIM:To determine the frequency of patients’vision survival and prognostic factors and evaluate clinical features in rhino-orbital ***:Forty-three eyes of 43 patients followed up with orbital mucormycosis infections were included in the *** characteristics of the patients,symptoms at admission,ophthalmologic and non-ophthalmologic examination findings,clinical findings during follow-up,medical and surgical procedures,and complications were *** survival was determined by assessing the incidence of mortality,and vision survival was defined as achieving a final visual acuity of at least light ***:Twenty-seven(62.8%)patients were male,and 16(37.2%)were *** the underlying disease status of the patients was examined,it was observed that all patients had an underlying disease and diabetes constituted the majority(65.2%).Periorbital swelling(69.8%)and ophthalmoplegia(53.5%)were the most common symptoms and findings at the admission of patients with mucormycosis *** disease resulted in death in 22(51.2%)*** presence of fever and shorter duration of antifungal therapy were associated with lower patient *** surgery was not found to be associated with the survival of the *** eye,loss of pupillary light reflex,and development of central retinal artery occlusion were associated with lower vision ***:This study presents one of the most extensive patient series in the literature on rhino-orbital *** the patients’symptoms at the time of admission and the clinical findings during the infection process will increase awareness about the disease.

关键词： mucormycosis rhino-orbital-mucormycosis orbital apex syndrome retinal arterial occlusion

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Effects of high glucose and severe hypoxia on the biological behavior of mesenchymal stem cells at various passages

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World Journal of Stem Cells 2024年第4期16卷 434-443页

作者： Fatimah Almahasneh Ejlal Abu-El-Rub Ramada R Khasawneh Rawan Almazari department of Basic Medical Sciences Faculty of MedicineYarmouk UniversityIrbid 21163Jordan

BACKGROUND Mesenchymal stem cells(MSCs)have been extensively studied for therapeutic potential,due to their regenerative and immunomodulatory *** passage and stress factors may affect the biological characteristics of MSCs,but the details of these effects have not been recognized *** To investigate the effects of stress factors(high glucose and severe hypoxia)on the biological characteristics of MSCs at different passages,in order to optimize the therapeutic applications of *** In this study,we investigated the impact of two stress conditions;severe hypoxia and high glucose on human adipose-tissue derived MSCs(hAD-MSCs)at passages 6(P6),P8,and ***,senescence and apoptosis were evaluated measuring WST-1,senescence-associated beta-galactosidase,and annexin V,*** Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control,while the extent of senescence did not change significantly under stress *** P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at *** cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage,while no change in apoptosis was *** the other hand,MSCs cultured under hypoxia showed decreased senescence,increased apoptosis and no significant change in proliferation when compared to the same conditions at *** These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages,and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.

关键词： Mesenchymal stem cells High glucose Hypoxia Stressful microenvironment Serial passage Senescence Apoptosis

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MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1

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Oncology Research 2024年第3期32卷 463-476页

作者： Hur SUN MASANORI KAWANO TATSUYA IWASAKI ICHRO ITONAGA YUTA KUBOTA HROSHI TSUMURA KAZUHRO TANAKA department of Orthopaedic Surgery Faculty of MedicineOita UniversityOita879-5503Japan

An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding *** study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 *** growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of ***329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell ***,a clinical comparison study was performed using the TCGA ***,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo *** miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic *** expression of proteins that indicate apoptosis increased *** cell cycle was arrested in the G0/G1 phase,and the G1/S transition was *** introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt *** experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues *** 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in *** cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR *** these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcom

关键词： MiR-329-3p TCF7L1 Wnt/β-catenin pathway Osteosarcoma Proliferation

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