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Genes & Diseases 2023年第5期10卷 1751-1754页

作者： tamara kleinbielen Felix Olasagasti Elena Beristain Amparo Viguri-Díaz Isabel Guerra-Merino Africa García-Orad Marian Mde Pancorbo BIOMICs Research Group Lascaray Research CenterUniversity of the Basque Country UPV/EHUVitoria-GasteizAraba 01006Spain Bioaraba Health Research Institute Vitoria-GasteizAraba 01009Spain Department of Biochemistry and Molecular Biology University of the Basque CountryUPV/EHUVitoria-GasteizAraba 01006Spain Molecular Genetics Laboratory Araba University HospitalOsakidetza Basque Health ServiceVitoria-GasteizAraba 01009Spain Pathology Department Araba University HospitalVitoria-GasteizAraba 01009Spain Department of Genetics Physical Anthropology and Animal PhysiologyUniversity of the Basque Country(UPV/EHU)LeioaBizkaia 48940Spain BioCruces Bizkaia Health Research Institute BarakaldoBizkaia 48903Spain Department of Zoology and Animal Biology.University of the Basque Country(UPV/EHU) LeioaBizkaia 48940Spain

N6-methyladenosine(m6A)is the most abundant modification in eukaryotic messenger RNA.1 This modification is dynamic,reversible,and mediated by proteins characterized as methyltransferases and demethylases.Recent investigations have found that aberrant expression of methyltransferases and demethylases results in m6A dysregulation and,in consequence,affects the biological functions in which this modification is involved.Indeed,m6A dysregulation affects the development and maintenance of various diseases,including cancer.2 For this reason,we explored the potential role that m6A modification has in invasive breast cancer of no special type(IBC-NST)and its molecular subtypes luminal A,luminal B HER2-,luminal B HER2+,HER2+,and triple-negative breast cancer(TNBC)whose degree of global m6A methylation has not yet been studied.

关键词： breast cancer HER2

Sex differences in the risk of retinopathy of prematurity:a systematic review,frequentist and Bayesian meta‑analysis,and meta‑regression

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World Journal of Pediatrics 2024年第4期20卷 340-352页

作者： tamara M.Hundscheid Silvia Gulden Mohamad F.Almutairi František Bartoš Giacomo Cavallaro Eduardo Villamor Division of Neonatology Department of PediatricsMosaKids Children’s HospitalMaastricht University Medical Center(MUMC+)School for Oncology and Reproduction(GROW)Maastricht UniversityP.Debyelaan 25.P.O.Box 58006202 AZ MaastrichtThe Netherlands Neonatal Intensive Care Unit Sant’Anna HospitalComoItaly Department of Psychology University of Amsterdam1001 NK AmsterdamThe Netherlands Neonatal Intensive Care Unit Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilanItaly

Background Retinopathy of prematurity(ROP)is generally considered to be more frequent in males than in females.However,it is not known whether sex differences in ROP affect all degrees of the condition,are global and have changed as neonatology has developed.We aimed to conduct a systematic review and meta-analysis of studies addressing sex differences in the risk of developing ROP.Methods PubMed/MEDLINE and Embase databases were searched.The frequentist,random-effects risk ratio(RR)and 95%confidence interval(CI)were calculated.Bayesian model averaged(BMA)meta-analysis was used to calculate the Bayes factors(BFs).The BF10 is the ratio of the probability of the data under the alternative hypothesis(H1)over the probability of the data under the null hypothesis(H0).Results We included 205 studies(867,252 infants).Frequentist meta-analysis showed a positive association between male sex and severe ROP(113 studies,RR=1.14,95%CI=1.07–1.22)but no association with any ROP(144 studies,RR=1.00,95%CI=0.96–1.03).BMA showed extreme evidence in favor of H1 for severe ROP(BF10=71,174)and strong evidence in favor of H0 for any ROP(BF10=0.05).The association between male sex and severe ROP remained stable over time and was present only in cohorts from countries with a high or high-middle sociodemographic index.Conclusions Our study confirms the presence of a male disadvantage in severe ROP but not in less severe forms of the disease.There are variations in the sex differences in ROP,depending on geographical location and sociodemographic level of the countries.

关键词： Oxidative stress Retinopathy of prematurity Sex characteristics

Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

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World Journal of Stem Cells 2024年第5期16卷 604-614页

作者： Edoardo Agosti Marco Zeppieri Mattia Ghidoni tamara Ius Alessandro Tel Marco Maria Fontanella Pier Paolo Panciani Division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Neurosurgery Unit Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy Clinic of Maxillofacial Surgery Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their im

关键词： Glioma stem cells Chemoresistance Radioresistance Molecular pathways Targeted therapies Systematic review

Current status and future perspectives on stem cell transplantation for spinal cord injury

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World Journal of Transplantation 2024年第1期14卷 189-209页

作者： Edoardo Agosti Marco Zeppieri Andrea Pagnoni Marco Maria Fontanella Alessandro Fiorindi tamara Ius Pier Paolo Panciani Division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Department of Medical and Surgical Specialties Radiological Sciencesand Public HealthUniversity of BresciaBrescia 25123BSItaly Neurosurgery Unit Head-Neck and NeuroScience DepartmentUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systematic reviews prioritize effectiveness,often overlooking safety and translational feasibility.This situation prompts inquiries regarding the readiness for clinical adoption.AIM To offer an up-to-date systematic literature review of clinical trial results concerning stem cell therapy for SCI.METHODS A systematic search was conducted across major medical databases[PubMed,Embase,Reference Citation Analysis(RCA),and Cochrane Library]up to October 14,2023.The search strategy utilized relevant Medical Subject Heading(MeSH)terms and keywords related to"spinal cord","injury","clinical trials","stem cells","functional outcomes",and"adverse events".Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI.RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,496 papers were initially identified,with 237 chosen for full-text analysis.Among them,236 were deemed eligible after excluding 170 for various reasons.These studies encompassed 1086 patients with varying SCI levels,with cervical injuries being the most common(42.2%).Bone marrow stem cells were the predominant stem cell type used(71.1%),with various administration methods.Follow-up durations averaged around 84.4 months.The 32.7%of patients showed functional improvement from American spinal injury association Impairment Scale(AIS)A to B,40.8%from AIS A to C,5.3%from AIS A to D,and 2.1%from AIS B to C.Sensory improvements were observed in 30.9%of patients.A relatively small number of adverse events were recorded,including fever(15.1%),headaches(4.3%),muscle tension(3.1%),and dizziness(2.6%),highlighting the potential for SCI recovery with stem cell therapy.CONCLUSION In the realm of SCI treatment,stem cell-based thera

关键词： Spinal cord injury Stem cell therapy Adverse events Functional outcomes Systematic review

A Golden Touch in the Design of Multifunctional Porphyrin Metallacages:Host-Guest Chemistry for Drug-Target Interactions

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CCS Chemistry 2024年第7期6卷 1662-1671页

作者： tamara Rodríguez-Prieto Darren Wragg Nicole Heiduk Mihyun Park Nicole Strittmatter Roland A.Fischer Angela Casini Guillermo Moreno-Alcántar Chair of Medicinal and Bioinorganic Chemistry Department of ChemistrySchool of Natural SciencesTechnical University of Munich85748 Garching b.München Professorship for Analytical Chemistry Department of ChemistrySchool of Natural SciencesTechnical University of Munich85748 Garching b.München Chair of Inorganic and MetalOrganic Chemistry Department of ChemistrySchool of Natural SciencesTechnical University of Munich85748 Garching b.München Munich Data Science Institute(MDSI) Technical University of Munich85748 Garching b.München

The use of three-dimensional self-assembled metallacages(MCgs)as multimodal drug platforms holds great promise.However,the synthesis of MCgs with increased complexity and functionality is a great challenge since understanding of the interaction of MCgs with biological targets is still limited.In this context,this work reports on the integration of a gold(III)porphyrin scaffold into a prismatic MCg structure and explores its application for multimodal therapy of cancer in vitro,namely enabling both photodynamic therapy and chemotherapy.Combining experimental approaches with a state-of-the-art metadynamics theoretical study,we discovered that the gold cage shows unprecedented host-guest interaction-driven selective stabilization of guanine-quadruplex(G4)structures-validated anticancer drug targets-disclosing a new mechanism to pursue in the design of supramolecular drugs.

关键词： gold metallacages porphyrins G4stabili-zation host-guestchemistry anticanceragents

Treatment for paraganglioma with stereotactic radiotherapy

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World Journal of Clinical Cases 2024年第16期12卷 2729-2737页

作者： Antonio Pontoriero Paola Critelli Marco Zeppieri Filippo Flavio Angileri tamara Ius Radiation Oncology Unit Department of BiomedicalDental Science and Morphological and Functional ImagesUniversity of MessinaMessina 98125Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Neurosurgery Unit Department of BiomedicalDental Science and Morphological and Functional ImagesUniversity of MessinaMessina 98125Italy Neurosurgery Unit Head-Neck and NeuroScience DepartmentUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Paragangliomas(PG)are rare neoplasms of neuroendocrine origin that tend to be highly vascularized,slow-growing,and usually sporadic.To date,common treatment options are surgical resection(SR),with or without radiation therapy(RT),and a watch-and-wait approach.AIM To evaluate the local control and effectiveness of exclusive fractionated stereotactic RT(FSRT)treatment in unresectable PG(uPG).METHODS We retrospectively evaluated patients with uPG(medically inoperable or refused SR)treated with FSRT with a Cyberknife System(Accuray Incorporated,Sunnyvale,California).Toxicity and initial efficacy were evaluated.RESULTS From May 2009 to January 2023,6 patients with a median age of 68(range 20-84)were treated with FSRT.The median delivered dose was 21 Gy(range 20-30 Gy)at a median isodose line of 75.5%(range 70%-76%)in 4 fractions(range 3-5 fractions).The median volume was 13.6 mL(range 12.4-65.24 mL).The median cumulative biological effective dose and equivalent dose in 2-Gy fractions were 70 Gy and 37.10 Gy respectively.Site of origin involved were the timpa-nojugular glomus(4/6),temporal bone,and cervical spine.In 1 of the 6 patients,the follow-up was insufficient;5 of 6 patients showed a 5-year overall survival and 5-year progression-free survival of 100%.We observed negligible toxicities during and after RT.The majority of patients showed stable symptoms during follow-up.Only 1 patient developed spine metastases.CONCLUSION Our preliminary results on this small cohort of patients suggest that FSRT could be an effective and safe alternative to SR.

关键词： Unresectable paraganglioma Fractionated stereotactic radiation therapy Cyberknife Neurosurgery Metastasis

Aging impairs the osteocytic regulation of collagen integrity and bone quality

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Bone Research 2024年第1期12卷 78-94页

作者： Charles A.Schurman Serra Kaya Neha Dole Nadja M.Maldonado Luna Natalia Castillo Ryan Potter Jacob P.Rose Joanna Bons Christina D.King Jordan B.Burton Birgit Schilling Simon Melov Simon Tang Eric Schaible tamara Alliston Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC Berkeley/UCSF Graduate Program in Bioengineering San FranciscoCA 94143USA Buck Institute for Research on Aging NovatoCA 94945USA Washington University in St Louis Department of OrthopedicsSt.LouisMO 63130USA Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Poor bone quality is a major factor in skeletal fragility in elderly individuals.The molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by osteocytes.We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material properties.We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses PLR.The control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)bone.This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests.The effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

关键词： maintain primarily integrity

Inventory of unintentional POPs emission from anthropogenic sources in Antarctica

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Advances in Polar Science 2022年第2期33卷 156-166页

作者： Sergey KAKAREKA tamara KUKHARCHYK Institute for Nature Management National Academy of Sciences of Belarus-Laboratory on Transboundary PollutionSkoriny 10 Minsk 220076Belarus

In spite of remote location and very limited human activities,Antarctica is affected by persistent organic pollutants(POPs).POPs investigation in Antarctica has a comparatively long history,but there are still large knowledge gaps in assessment of their emission into environment.In the paper the results of the first inventory of unintentional POPs emission from anthropogenic sources in Antarctica for modern period and preliminary estimate for the late 1980s are presented.Assessment of dioxin/furans(PCDD/Fs)emission in different media,as well as polychlorinated biphenyls(PCBs)and hexachlorobenzene(HCB)in air is based on methodology of emission factors and indicators of human activity.The following sources of POPs emission have been estimated:power generation and heating,waste incineration,mobile sources and open burning of waste(in the past).According to the data obtained,annual PCDD/Fs air emission for modern period comprises 60.74 mg toxic equivalent(TEQ),PCBs-5.09 mg TEQ,and HCB-457.6 mg.Additionally 2.5 mg TEQ of dioxin/furans is released to residues,so total PCDD/Fs emission is amounted 63.23 mg TEQ.Waste incineration makes the greatest contribution to POPs emission(96% of PCDD/Fs,98%of PCBs and 36% of HCB air emission).In late 1980s open burning of waste was the major source of POPs.Retrospective assessment shows that over a 30-year period air emissions of PCDD/Fs decreased about 13 times,PCBs-15 times and HCB-57 times,primarily due to the prohibition of open burning of waste in compliance with the Protocol on Environmental Protection to the Antarctic Treaty requirements.

关键词： persistent organic pollutants emission inventory PCDD/Fs PCBs HCB

Transplanted: Chinese Herbal Medicine in the United States, 1800-1911

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Chinese Medicine and Culture 2023年第4期6卷 357-366页

作者： tamara Venit Shelton History Department Claremont McKenna CollegeClaremontCA 91711USA

Chinese medicine has a long history in the United States, dating back to its colonial period and extending up to the present. This essay focuses on the earliest generation of practitioners of traditional Chinese medicine in the United States. Although acupuncture is the modality most commonly associated with Chinese medicine in today's medical marketplace, up until the 1970s, Chinese healers in the United States typically specialized in herbalism. Well before mass emigration from China to the United States began, Chinese material medica crossed the oceans, in both directions: Chinese medicinal teas and herbs came west while Appalachian ginseng went east. Beginning in the 1850s, Chinese immigrants came to the United States and transplanted their health practices, sometimes quite literally by propagating medicinal plants in their adopted home. Over time, Chinese doctors learned how to sell their services to non-Chinese patients by presenting herbalism as “nature's remedies.”

关键词： American medicine Alternative medicine Chinese herbalism Natural medicine

Association between innate immunity gene polymorphisms and neonatal sepsis development:a systematic review and meta-analysis

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World Journal of Pediatrics 2022年第10期18卷 654-670页

作者： tamara Sljivancanin Jakovljevic Jelena Martic Jelena Jacimovic Nadja Nikolic Jelena Milasin Tanja Lazić Mitrović Department of Neonatology The Obstetrics and Gynecology Clinic“Narodni Front”BelgradeSerbia School of Medicine University of BelgradeBelgradeSerbia Department of Neonatology Mother and Child Health Care Institute of Serbia“Dr Vukan Cupic”BelgradeSerbia Central Library School of Dental MedicineUniversity of BelgradeBelgradeSerbia Department of Human Genetics School of Dental MedicineUniversity of BelgradeBelgradeSerbia

Background The aim of this meta-analysis was to analyze all available data from studies investigating associations between polymorphisms in genes responsible for innate immunity and neonatal sepsis development.Methods A comprehensive literature search,reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-S guidelines,was performed with no language restriction.Studies derived using the PICO(population,intervention,comparison and outcomes)strategy,with data on the genotype distribution for innate immunity gene polymorphisms in newborns with and without sepsis.Data were analyzed using Review Manager.The Cochran–Mantel–Haenszel test was used to calculate odds ratios with 95%confidence intervals.Heterogeneity was tested using the I2 index.Results From a total of 9428 possibly relevant articles,33 qualified for inclusion in this systematic review.According to the STrengthening the REporting of Genetic Association Studies,23 studies were found to be of moderate quality,while 10 were of low quality.The results showed an association of the mannose-binding lectin(MBL)exon 1 genetic polymorphism with the risk of culture-proven sepsis.Toll-like receptor(TLR)4 rs4986791 genotype distribution suggests its association with the increased risk of culture-proven sepsis.The certainty of evidence per GRADE(Grading of Recommendations,Assessment,Development,and Evaluation)varied from very low to low.Publication bias was not detected.Conclusions Out of the 11 investigated single-nucleotide polymorphisms,this meta-analysis found a possible association between the risk for culture-proven sepsis and MBL exon 1 and TLR4 rs4986791 polymorphisms.There is an evident need for larger well-designed,multicentric observational studies investigating inflammatory gene polymorphisms in neonatal sepsis.

关键词： Genetic Immunity Innate Neonatal sepsis Polymorphism