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Targeting hormone-resistant breast cancer cells with docetaxel:a look inside the resistance

Cancer Drug Resistance 2023年第1期6卷 103-115页

作者： Alexander M.Scherbakov Anna A.Basharina Danila V.Sorokin Ekaterina I.Mikhaevich Iman E.Mizaeva alexandra l.mikhaylova Tatiana A.Bogush Mikhail A.Krasil’nikov Department of Experimental Tumor Biology Blokhin N.N.National Medical Research Center of OncologyMoscow 115522Russian Federation Group of Molecular Tumor Markers Blokhin N.N.National Medical Research Center of OncologyMoscow 115522Russian Federation

Aim:The study aims to analyze the effect of long-term incubation of ERα-positive MCF7 breast cancer cells with 4-hydroxytamoxifen(HT)on their sensitivity to tubulin polymerization inhibitor ***:The analysis of cell viability was performed by the MTT *** expression of signaling proteins was analyzed by immunoblotting and flow ***αactivity was evaluated by gene reporter *** establish hormone-resistant subline MCF7,breast cancer cells were treated with 4-hydroxytamoxifen for 12 ***:The developed MCF7/HT subline has lost sensitivity to 4-hydroxytamoxifen,and the resistance index was *** Akt activity(2.2-fold)and decreased ERαexpression(1.5-fold)were revealed in MCF7/HT *** activity of the estrogen receptorαwas reduced(1.5-fold)in MCF7/*** of class Ⅲβ-tubulin expression(TUBB3),a marker associated with metastasis,revealed the following trends:higher expression of TUBB3 was detected in triple-negative breast cancer MDA-MB-231 cells compared to hormone-responsive MCF7 cells(Plowest expression of TUBB3 was found in hormone-resistant MCF7/HT cells(MCF7/HTly 1:2:4).High TUBB3 expression strongly correlated with docetaxel resistance:IC_(50)value of docetaxel for MDA-MB-231 cells was greater than that for MCF7 cells,whereas resistant MCF7/HT cells were the most sensitive to the *** accumulation of cleaved PARP(a 1.6-fold increase)and Bcl-2 downregulation(1.8-fold)were more pronounced in docetaxel-treated resistant cells(Plin D1 decreased(2.8-fold)only in resistant cells after 4 nM docetaxel treatment,while this marker was unchanged in parental MCF7 breast cancer ***:Further development of taxane-based chemotherapy for hormone-resistant cancer looks highly promising,especially for cancers with low TUBB3 expression.

关键词： Cancer docetaxel 4-hydroxytamoxifen classⅢβ-tubulin resistance breast cancer estrogen receptors alpha

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The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens

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Infectious Microbes & Diseases 2024年第2期6卷 65-73页

作者： alexandra Stream Ross Corriden Simon Döhrmann Richard l.Gallo Victor Nizet Ericka l.Anderson Division of Host-Microbe Systems and Therapeutics Department of PediatricsUniversity of California San Diego School of MedicineLa JollaCaliforniaUSA Department of Dermatology University of California San Diego School of MedicineLa JollaCaliforniaUSA Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San DiegoLa JollaCaliforniaUSA

Vitamin A and its biologically active derivative,retinoic acid(RA),are important for many immune ***,in particular,is essential for the development of immune cells,including neutrophils,which serve as a front-line defense against *** vitamin A deficiency has been linked to higher susceptibility to infections,the precise role of vitamin A/RA in host-pathogen interactions remains poorly ***,we provided evidence that RA boosts neutrophil killing of methicillin-resistant Staphylococcus aureus(MRSA).RA treatment stimulated primary human neutrophils to produce reactive oxygen species,neutrophil extracellular traps and the antimicrobial peptide cathelicidin(ll-37).Because RA treatment was insufficient to reduce MRSA burden in an in vivo murine model of skin infection,we expanded our analysis to other infectious *** did not affect the growth of a number of common bacterial pathogens,including MRSA,Escherichia coli K1 and Pseudomonas aeruginosa;however,RA directly inhibited the growth of group A Streptococcus(GAS).This antimicrobial effect,likely in combination with RA-mediated neutrophil boosting,resulted in substantial GAS killing in neutrophil killing assays conducted in the presence of ***,in a murine model of GAS skin infection,topical RA treatment showed therapeutic potential by reducing both skin lesion size and bacterial *** findings suggest that RA may hold promise as a therapeutic agent against GAS and perhaps other clinically significant human pathogens.

关键词： retinoic acid neutrophil bacterial infection Staphylococcus aureus group A Streptococcus neutrophil extracellular traps antimicrobial peptide cathelicidin

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Weight regain after intragastric balloon for pre-surgical weight loss

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2040-2046页

作者： Danielle Abbitt Kevin Choy alexandra Kovar Teresa S Jones Krzysztof J Wikiel Edward l Jones Department of Surgery University of ColoradoAuroraCO 80045United States Department of Surgery Rocky Mountain Regional Veteran Affairs Medical CenterAuroraCO 80045United States

BACKGROUND Over one-third of Americans carry the diagnosis of obesity,many also with obesity-related *** can place patients at increased risk of operative and postoperative *** intragastric balloon has been shown to aid in minor weight loss,however its weight recidivism in patients requiring short interval weight loss has not been well *** To evaluate weight loss,ability to undergo successful elective surgery after intragastric balloon placement,and weight management after balloon *** This study is a retrospective review of patients in a single academic institution undergoing intragastric balloon placement from 2019-2023 to aid in weight loss prior to undergoing elective *** outcomes including weight loss,duration of balloon placement,successful elective surgery,weight regain postballoon and post-procedure complications were *** criteria included those with balloon in place at time of *** Thirty-three patients completed intragastric balloon therapy from 2019-2023 as a bridge to elective *** patients were required to participate in a 12-month weight management program to be eligible for balloon *** surgeries included incisional hernia repair,umbilical hernia repair,inguinal hernia repair,and knee and hip *** average age at placement was 53 years±11 years,majority(91%)were *** average duration of intragastric balloon therapy was 186 days±41 *** average weight loss was 14.0 kg±7.4 kg and with an average percent excess body weight loss of 30.0%(7.9%-73.6%).Over half of the patients(52.0%)achieved the goal of 30-50 lbs(14-22 kg)weight ***-one patients(64%)underwent their intended elective surgery,2 patients(6%)deferred surgery due to symptom relief with weight loss ***-one of the patients(64%)have documented weights in 3 months after balloon removal,in these patients the majority(76%)gained weight after balloon *** pat

关键词： Intragastric balloon Weight loss Obesity Bariatric Body mass index

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*** model of riboflavin transporter deficiency(RTD)disorder reveals deficits in synaptic transmission and movement

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Genes & Diseases 2024年第4期11卷 120-123页

作者： Ramesh K.Narayanan Gonzalo Perez-siles Kamila A.Marzec alexandra Boyling Brent Neumann Manoj P.Menezes Marina l.Kennerson Northcott Neuroscience laboratory ANZAC Research Institute-Sydney Local Health DistrictSydneyNSW 2139Australia Sydney Medical School University of SydneySydneyNSw 2050Australia ANZAC Research Institute-Sydney local Health District SydneyNSW 2139Australia Neuroscience Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVictoria 3800Australia TY Nelson Department of Neurology and Neurosurgery and Kids Neuroscience Children's Hospital at WestmeadWestmeadSydneyNSW2145Australia Paediatrics and Child Health The University of SydneySydneySydneyNSW 2145Australia Molecular Medicine laboratory Concord General Repatriation HospitalSydneyNSW 2139Australia

Riboflavin transporter deficiency(RTD),previously known as Brown-Vialetto-Van laere syndrome,is a childhoodonset neurodegenerative disorder characterized by sensory and motor neuron degeneration causing ataxia,muscle weakness,optic atrophy,and respiratory *** in SlC52A2 and SlC52A3,solute carrier family members that encode riboflavin(RF)transporters RFVT2 and RFVT3,are known to cause RTD types 2 and 3,respectively.

关键词： RTD degeneration TD

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Effect of vaccinations and school restrictions on the spread of COVID-19 in different age groups in Germany

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Infectious Disease Modelling 2024年第4期9卷 1250-1264页

作者： Christiane Dings Dominik Selzer Nicola luigi Bragazzi Eva Mohler Markus Wenning Thomas Gehrke Ulf Richter alexandra Nonnenmacher Folke Brinkmann Tobias Rothoeft Michael Zemlin Thomas lücke Thorsten lehr Department of Clinical Pharmacy Saarland University66123SaarbrückenGermany Department of Child and Adolescent Psychiatry Saarland University Hospital66421HomburgGermany Medical Association Westfalen-Lippe48151MünsterGermany School of Education and Psychology Siegen University57072SiegenGermany University Children's Hospital Ruhr University44791BochumGermany University Children's Hospital Airway Research Center North(ARCN)German Center for Lung Research(DZL)LübeckGermany Department of General Pediatrics and Neonatology Saarland University Hospital66421HomburgGermany

With the emergence of SARS-CoV-2,various non-pharmaceutical interventions were adopted to control virus transmission,including school ***,the introduction of vaccines mitigated not only disease severity but also the spread of *** study leveraged an adapted SIR model and non-linear mixed-effects modeling to quantify the impact of remote learning,school holidays,the emergence of Variants of Concern(VOCs),and the role of vaccinations in controlling SARS-CoV-2 spread across 16 German federal states with an age-stratified *** highlight a significant inverse correlation(Spearman's ρ=0.92,pll age ***-parameter estimation using the observed number of cases stratified by federal state and age allowed to assess the effects of school closure and holidays,considering adjustments for vaccinations and spread of VOCs over ***,modeling revealed significant(pl children(0-4),children(5-11),adolescents(12-17),adults(18-59),and the elderly(60+).The transition to remote learning emerged as a critical measure in significantly reducing infection rates among children and adolescents(plderly during these periods,suggesting a shift in infection networks due to altered caregiving ***,during school holiday periods,infection rates among adolescents mirrored those observed when schools were *** exercises based on the model provided evidence that COVID-19 vaccinations might serve a dual purpose:they protect the vaccinated individuals and contribute to the broader community's safety.

关键词： COVID-19 Vaccination Non-pharmaceutical interventions Age Mathematical modeling

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Rare dentin defects:Understanding the pathophysiological mechanisms of COlXVA1 mutations

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Genes & Diseases 2024年第5期11卷 1-5页

作者： Isaac Maximiliano Bugueno Tristan Rey alexandra Jimenez-Armijo Marzena Kawczynski Naji Kharouf Marie-Cecile Maniere Yann Herault Agnes Bloch-Zupan Virginie Haushalterlaugel Institute of Genetics and Molecular and Cellular Biology(IGBMC) CNRS-UMR7104INSERM U1258Universitede StrasbourgIllkirch 67400France Faculty of Dentistry Universitede StrasbourgStrasbourg 67000France Institute of Advanced Studies(USIAS) Universitede StrasbourgStrasbourg 67045France Reference Center for Rare Oral and Dental Diseases(CRMR-O-Rares) Oral Medicine and Surgery DepartmentHopitaux Universitaires de Strasbourg(HUS)Strasbourg 67000France Rare Diseases Health Network“TETE COU”&European Reference Network ERN CRANIO Strasbourg 67000France “Institut de Genetique Medicale d’Alsace” Laboratory of Genetic DiagnosticHopitaux Universitaires de Strasbourg(HUS)Strasbourg 67000France Biomaterials and Bioengineering laboratory Inserm UMR_S 1121Strasbourg 67000France Orofacial Development and Regeneration Faculty of MedicineInstitute of Oral BiologyCentre of Dental MedicineUniversity of ZurichZurich 8032Switzerland

Dentin is a mineralized tissue with a chemical composition similar to bone but with a higher mineralized density and *** constitutes the central structure of the tooth between the internal pulp and external enamel toward the oral cavity or cementum toward the underlying *** dentin defects occur in a variety of rare genetic *** can manifest as“isolated”occurrences such as in dentinogenesis imperfecta(DI)or dentin dysplasia(DD)or can be associated with other symptoms in diseases such as osteogenesis imperfecta,Goldblatt syndrome,microcephalic osteodysplastic primordial dwarfism type Ⅱ,among others.

关键词： diseases den rigidity

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Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 57-68页

作者： Yanni li Eline H.van den Berg Alexander Kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu Esteban A.lopera-Maya alexandra Zhernakova lifelines Cohort Study Vincent E.de Meijer Serena Sanna Robin P.F.Dullaart Hans Blokzijl Eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma Department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFlD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FlI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics lifelines Initiative(UGlI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3l1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPlA3,TM6SF2,and *** of FlI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGlI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FlI(UGlI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3l1 and GCM1)were replicated in the FlI *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FlI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFlD Genome-wide association study Fatty liver index Magnetic resonance imaging proton density fat fraction

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Clinical and Demographic Profile of Women with Uterine Fibroids living in Puerto Rico

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Open Journal of Obstetrics and Gynecology 2024年第9期14卷 1347-1362页

作者： Edwin Y. Soto-Velázquez Alexander J. Jaramillo-Cañas Shania N. Aponte-Paris Gabriela V. Martínez-Marrero Irazu S. Guinan Gabrielle A. Rivera-Maldonado alexandra Novas Pedro l. Cruz-Rosa Idhaliz Flores-Caldera Maricarmen Colón-Diaz Department of Physiology and Pathology San Juan Bautista School of Medicine Caguas Puerto Rico United States Ponce Research Institute Ponce Health Sciences University Ponce Puerto Rico United States

Introduction: Uterine leiomyomas, or fibroids, are prevalent benign tumors affecting up to 70% of reproductive-age women in the United States, significantly impacting productivity and quality of life. Despite their commonality, the epidemiology and clinical patterns of leiomyomas in Puerto Rico remain inadequately researched. Methods: This study conducted a secondary data analysis using clinical, menstrual cycle characteristics, and demographic data from self-administered questionnaires of women undergoing diagnostic laparoscopy for endometriosis in Puerto Rico. Chi-square tests and t-tests analyzed categorical and continuous variables, respectively (p Results: Among 1,610 endometriosis cases, 312 included uterine fibroids. Prevalence estimates were 10.3% (40 years). Primiparous women averaged 22.14 years, with 40.71% having 2 - 3 pregnancies and 26.28% experiencing miscarriages. Symptoms included infertility (29.5%), dyspareunia (40.7%), severe pain (50%), and dysmenorrhea (75.6%). Comorbidities included ovarian cysts (52.2%) and abnormal uterine bleeding (37.8%). Conclusions: Advanced age, parity, and comorbidities like diabetes and hypertension were prevalent in our cohort. Understanding the epidemiological profile of women living in Puerto Rico with uterine fibroids is crucial for improving diagnostic awareness and enhancing patient care.

关键词： Uterine Fibroids Puerto Rico Epidemiology Dysmenorrhea Abnormal Uterine Bleeding

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Microbial community coalescence and nitrogen cycling in simulated mortality decomposition hotspots

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Ecological Processes 2023年第1期12卷 608-624页

作者： Sarah W.Keenan alexandra l.Emmons Jennifer M.DeBruyn Department of Geology and Geological Engineering South Dakota School of Mines and Technology501 East St.Joseph StreetRapidSD 57701USA Department of Anthropology University of TennesseeKnoxvilleTNUSA Department of Biosystems Engineering and Soil Science University of Tennessee2506 E.J.Chapman DriveKnoxvilleTN 37996USA

Background The pulsed introduction of dead plant and animal material into soils represents one of the primary mechanisms for returning organic carbon(C)and nitrogen(N)compounds to biogeochemical *** of animal carcasses provides a high C and N resource that stimulates indigenous environmental microbial communities and introduces non-indigenous,carcass-derived microbes to the ***,the dynamics of the coalesced microbial communities,and the relative contributions of environment-and carcass-derived microbes to C and N cycling are *** test whether environment-derived,carcass-derived,or the combined microbial communities exhibited a greater influence on C and N cycling,we conducted controlled laboratory experiments that combined carcass decomposition fluids and soils to simulate carcass decomposition *** selectively sterilized the decomposition fluid and/or soil to remove microbial communities and create different combinations of environment-and carcass-derived communities and incubated the treatments under three temperatures(10,20,and 30℃).Results Carcass-derived bacteria persisted in soils in our simulated decomposition scenarios,albeit at low *** communities had higher respiration rates at 10 and 30℃ compared to soil or carcass communities ***,at higher temperatures,mixed communities had reduced diversity,but higher respiration,suggesting functional *** communities treatments also provided evidence that carcass-associated microbes may be contributing to ammonification and denitrification,but that nitrification is still primarily carried out by native soil *** Our work yields insight into the dynamics of microbial communities that are coalescing during carcass decomposition,and how they contribute to recycling carcasses in terrestrial ecosystems.

关键词： Carcass decomposition Microcosm Nitrogen Carbon Biogeochemical cycling Coalescence

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Moving of a submarine under an ice cover in fluid of finite depth

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Journal of Hydrodynamics 2019年第3期31卷 562-569页

作者： alexandra V. Pogorelova Vitali l. Zemlyak Victor M. Kozin Sholom-A leichem Priamursky State University Birobidzhan Russia Institute of Machining and Metallurgy FEB RAS Komsomolsk-na-Amure Russia

The influence of a basin depth on ice cover deflections, when a submarine moves under it in fluid, is experimentally and theoretically analyzed. For a theoretical research the ice cover is modelled by an elastic floating plate, and the submarine is modelled by a source-sink system in a fluid flow. The problem is solved by means of asymptotic analysis and integral transformations. The experimental study is conducted with submarine models in the pool with the sizes l*B*H= 10m*3m*lm . The ice cover for experiments is modelled in two ways. The first way is the thin ice plate received by freezing of the surface layer of water at low temperatures. In the second case the rubber sheet floating on a reservoir surface is used. The special velocity (the velocity at which maximum values of the wave height are reached) is analyzed. It is obtained that the decrease of the basin depth leads to decrease of the special speed. For small speeds (less than the special speed) there is the fact that the basin depth decrease leads to the increase of the height of the flexural-gravity wave.

关键词： Ice cover submarine flexural gravity wave source-sink system

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