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Analyzing stem cell dynamics： use of cutting edge genetic approaches in model organisms

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Frontiers in Biology 2015年第1期10卷 1-10页

作者： Gary R. HIMe Nicole SIDDALL Katja HORVAY helen e. abud Department of Anatomy and Neuroseienee University of Melbourne VIC 3010 Australia Department of Anatomy and Developmental Biology Monash University Clayton VIC 3800 Australia

Regeneration of many cell types found in adult organs relies upon the presence of relatively small pools of undifferentiated stem cells. Initial studies that attempted to isolate stem cells and propagate them in vitro have been complemented by analysis of stem cells in their endogenous tissues where they are subject to a variety of regulatory cues. This has been facilitated by the advent of new methods for lineage tracing and genetic manipulation of stem cells and their associated niche cells. The picture that is emerging is that different stem cell populations utilize diverse processes to ensure maintenance of the stem cell pool accompanied by production of cells committed to regenerate differentiated cells.

关键词： stem cells Drosophila mouse testis intestine lineage tracing

CD44 and CD221 directed magnetic cubosomes for the targeted delivery of helenalin to rhabdomyosarcoma cells

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Nano Research 2023年第2期16卷 2915-2926页

作者： Hakmin Mun Yuriy Chaban Tanveer A.Tabish Nanasaheb Thorat Nathan Cowieson CDavid Owen helen e.Townley Nuffield Department of Women’s and Reproductive health University of OxfordOxford OX39DUUK electron Bio-Imaging Centre Diamond Light SourceDidcot OX110DEUK Radcliffe Department of Medicine University of OxfordOxford OX37BNUK B21 Diamond Light SourceDidcot OX110DEUK Department of engineering Science University of OxfordOxford OX13PJUK

Confining chemotherapy to tumour sites by means of active targeting nanoparticles(NPs)may increase the treatment effectuality while reducing potential side *** are one of the next-generation drug delivery nanocarriers by virtue of their biocompatibility and bioadhesion,sizeable payload encapsulation and high ***,an active tumour targeting system towards rhabdomyosarcoma(RMS)cells was *** were loaded with helenalin(a secondary metabolite from Arnica plants),which we have previously shown to induce apoptosis in RMS *** functionalization of the cubosomes was accomplished to enable binding to membrane receptors and translocation under a magnetic *** cells overexpress CD44 and CD221 on their membrane surface and,therefore,hyaluronic acid(HA,a ligand for CD44)and antibodies(Abs)against CD221 were coupled to cubosomes via electrostatic attraction and the thiol-Michael reaction,*** of the cubic phase NPs was achieved by embedding superparamagnetic iron oxide NPs(SPIONPs)into the cubic ***-function and multi-function cubosomes had Im3m cubic phase structures with well-organized lattice *** with 2%HA or anti-CD221 half Abs and/or 1%SPIONPs showed significantly higher uptake into RMS cells compared to unfunctionalized ***44 and CD221 directed magnetic(triple-function)cubosomes were capable of internalizing into RMS cells in an energy-independent ***-laden triple functionalized cubosomes showed limited impact on the viability of control fibroblast cells,while they induced a high degree cytotoxicity against RMS *** tumour cell death was observed in both two-dimensional(2D)culture and three-dimensional(3D)tumour spheroids.

关键词： cubosome active targeting rhabdomyosarcoma helenalin nanoparticle functionalization

Influence of biological sex and exercise on murine cardiac metabolism

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Journal of Sport and Health Science 2022年第4期11卷 479-494页

作者： Kyle Fulghum helen e.Collins Steven P.Jones Bradford G.Hill Diabetes and Obesity Center Department of MedicineDivision of Environmental MedicineChristina Lee Brown Envirome InstituteUniversity of LouisvilleLouisvilleKY 40202USA Department of Physiology University of LouisvilleLouisvilleKY 40202USA

Although the structural and functional effects of exercise on the heart are well established,the metabolic changes that occur in the heart during and after exercise remain *** this study,we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill *** the exercise bout,we also recorded blood lactate,glucose,and ketone body levels and measured cardiac mitochondrial *** both male and female mice,moderate-and high-intensity exercise acutely increased blood lactate *** both sexes,low-and moderate-intensity exercise augmented circulating 3-hydroxybutryrate levels immediately after the exercise bout;however,only in female mice did high-intensity exercise increase 3-hydroxybutyrate levels,with significant increases occurring 1 h after the exercise *** metabolomics analyses of sedentary female and male hearts suggest considerable sex-dependent differences in basal cardiac metabolite levels,with female hearts characterized by higher levels of pantothenate,pyridoxamine,homoarginine,tryptophan,and several glycerophospholipid and sphingomyelin species and lower levels of numerous metabolites,including acetyl coenzyme A,glucuronate,gulonate,hydroxyproline,prolyl-hydroxyproline,carnosine,anserine,and carnitinylated and glycinated species,as compared with male *** after a bout of treadmill exercise,both male and female hearts had higher levels of corticosterone;however,female mice showed more extensive exercise-induced changes in the cardiac metabolome,characterized by significant,time-dependent changes in amino acids(e.g.,serine,alanine,tyrosine,tryptophan,branched-chain amino acids)and the ketone body *** from experiments using isolated cardiac mitochondria suggest that high-intensity treadmill exercise does not acutely affect respiration or mitochondrial coupling;however,female cardiac mitochondria demonstrate generally higher adenosi

关键词： Ketone bodies Metabolomics Mitochondria Physical activity Sex difference

Histone deacetylase inhibitors as a novel therapeutic approach for pheochromocytomas and paragangliomas

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Oncology Research 2022年第5期30卷 211-219页

作者： ASPASIA MANTA SPYRIDON KAZANAS STeFANOS KARAMAROUDIS helen GOGAS DIMITRIOS C.ZIOGAS endocrine Unit Second Department of Internal Medicine Propaedeutic&Research InstituteMedical SchoolNational and Kapodistrian University of AthensAttikon University HospitalAthens12461Greece First Department of Internal Medicine Medical SchoolNational and Kapodistrian University of AthensLaikon General HospitalAthens11527Greece Department of Obstetrics&Gynecology General Hospital of Elefsina ThriassioElefsina19600Greece

epigenetic mechanisms,such as DNA methylation and histone modiﬁcations(e.g.,acetylation and deacetylation),are strongly implicated in the carcinogenesis of various *** transcription,the expression and functionality of coding gene products are altered following the histone acetylation and *** processes are regulated by histone acetyltransferases(HATs)and histone deacetylases(HDACs),*** inhibitors(HDACis)have been developed as promising therapeutic agents,to limit exposure to traditional and toxic chemotherapies and offer more alternatives for some speciﬁc malignant diseases with limited ***,these agents affect many intracellular pathways,including cell cycle arrest,apoptosis and differentiation,and their mechanism of action mainly depends on the type of ***,ﬁve HDACis have been approved for the treatment of several hematological malignancies(e.g.,T-cell lymphoma subtypes and multiple myeloma);while,many of them are tested for further therapeutic indications in solid tumors(e.g.,colorectal,thyroid,breast,lung and pancreatic cancer).Herein,we review the literature and gather all available evidence,from in vitro and in vivo data to clinical trial results,that recognizes the antitumor activity of HDACis on pheochromocytomas and paragangliomas;and supports their clinical implementation in the treatment of these rare neuroendocrine tumors at metastatic setting.

关键词： HDACis HDAC inhibitors Neuroendocrine tumors epigenetics Histone deacetylation Cancer

Successful management of a mixed epithelial and stromal renal tumor masquerading as lower pole renal cyst:A laparoscopic deroofing approach

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UroPrecision 2024年第1期2卷 36-39页

作者： Alain M.Mukendi emelia K.C.de Heer-Menlah Phaladi Charles e.Mathye Department of Surgery Division of UrologyHelen Joseph HospitalUniversity of the WitwatersrandJohannesburgSouth Africa

Background:Renal cysts are common in clinical practice,but some may harbor rare pathological entities such as mixed epithelial and stromal tumors(MeST).Imaging studies are crucial for accurate *** laparoscopic deroofing is an established approach for symptomatic renal cysts,encountering MeST within a cyst is *** Presentation:We present the case of a 37-year-old female who presented with persistent left flank *** revealed a large renal cyst in the lower pole of the left kidney,classified as Bosniak *** analgesia,the patient's symptoms persisted,leading to a laparoscopic deroofing *** examination postprocedure revealed a *** patient reported complete resolution of symptoms at the 3-month ***:This unique case presents the successful identification and surgical management of a MeST masquerading as a lower pole renal cyst through laparoscopic *** also contributes to the existing literature by highlighting the importance of considering rare pathological entities in the evaluation of renal cysts and the value of laparoscopic techniques in their management.

关键词： laparoscopic deroofing mixed epithelial and stromal tumor renal cyst renal tumor

Likelihood-based estimation and prediction for a measles outbreak in Samoa

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Infectious Disease Modelling 2023年第1期8卷 212-227页

作者： David Wu helen Petousis-Harris Janine Paynter Vinod Suresh Oliver J.Maclaren Department of engineering Science University of AucklandGraftonAuckland1010New Zealand Department of General Practice and Primary Health Care University of AucklandGraftonAuckland1023New Zealand Auckland Bioengineering Institute University of AucklandGraftonAuckland1010New Zealand

Prediction of the progression of an infectious disease outbreak is important for planning and coordinating a *** equations are often used to model an epidemic outbreak's behaviour but are challenging to ***,these models can suffer from misspecification,which biases predictions and parameter *** models can help with misspecification but are even more expensive to simulate and perform inference ***,we develop an explicitly likelihood-based variation of the generalised profiling method as a tool for prediction and inference under model *** approach allows us to carry out identifiability analysis and uncertainty quantification using profile likelihood-based methods without the need for *** provide justification for this approach by introducing a new interpretation of the model approximation component as a stochastic *** preserves the rationale for using profiling rather than integration to remove nuisance parameters while also providing a link back to stochastic *** applied an initial version of this method during an outbreak of measles in Samoa in 2019e2020 and found that it achieved relatively fast,accurate *** we present the most recent version of our method and its application to this measles outbreak,along with additional validation.

关键词： Generalised profiling Likelihood-based inference Profile likelihood Parameter estimation Bootstrap Measles

Interactions among age, adiposity, bodyweight, lifestyle factors and sex steroid hormones in healthy Singaporean Chinese men

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Asian Journal of Andrology 2007年第5期9卷 611-621页

作者： Victor H. H. Goh Terry Y. Y. Tong helen e e Mok Baharudin Said Department of Obstetrics and Gynaecology National University of Singapore National University Hospital Kent Ridge119074 Singapore Core Lab General Clinical Research Center LA BioMed at Harbor-UCLA Medical Center and Department of Medicine Division of Endocrinology David Geffen School of Medicine 1124W Carson Street Torrance CA 90502 USA

Aim： To examine the inter-relationships among age, lifestyle factors, anthropometric parameters, percent body fat and steroid hormone parameters in 531 healthy Singaporean Chinese men aged between 29 and 72 years old. Methods： Various lifestyle parameters were quantified through a survey, and testosterone （T）, estradiol （e2）, dehydroepiandrosterone sulphate （DHeAS） and sex hormone binding globulin （SHBG） were measured using established methods. Anthropometric parameters were collected and computed, and percent body fat （Siri） was measured using the DeXA scanner. Results： SHBG, DHeAS, bioavailable-T （Bio-T）, e2, Siri, Ht, W/H, W/Ht and work stress were independently correlated with age. Using multivariate analyses and adjusting for age and other related factors, exercise, smoking and alcohol consumption have positive impacts on androgen levels and body composition. However, black and green tea consumption was associated with negative effects on body composition and with higher levels of e2 and Free estradiol Index （FeI）. Men with shorter sleep duration had significantly lower T levels as compared to those with 6 h or more of nightly sleep. Higher T levels were associated with lower levels of adiposity and other indices of adiposity, whereas higher e2 levels were related to higher levels of adiposity. Men with higher DHeAS were significantly taller and heavier than those with low DHeAS levels. Conclusion： The study showed the close interactions among the gonadal/adrenal and metabolic compartments, with age being a key determinant in their interactions. Lifestyle factors such as exercise, smoking, sleeping and alcohol and tea consumption might play significantly roles in determining the status of health in men.

关键词： age testosterone sex hormone binding globulin estradiol dehydroepiandrosterone sulphate bioavailable-testosterone body fat exercise smoking alcohol tea coffee stress sleep

Regional variation in routes to diagnosis of cholangiocarcinoma in england from 2006 to 2017

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World Journal of Gastroenterology 2023年第24期29卷 3825-3842页

作者： Amy Zalin-Miller Sophie Jose Craig Knott Lizz Paley Daniela Tataru helen Morement Mireille B Toledano Shahid A Khan Department of Analytics Health Data Insight CICCambridge CB215XEUnited Kingdom Disease Registration Service NHS EnglandLondon E144PUUnited Kingdom CeO AMMFLondon CM241QWUnited Kingdom MRC Centre for environment and Health School of Public HealthImperial College LondonLondon SW72BXUnited Kingdom Liver Unit Division of Digestive DiseasesImperial College LondonLondon W21NYUnited Kingdom

BACKGROUND Incidence of cholangiocarcinoma(CCA)is rising,with overall prognosis remaining very *** for the high mortality of CCA include its late presentation in most patients,when curative options are no longer feasible,and poor response to systemic therapies for advanced *** presentation presents a large barrier to improving outcomes and is often associated with diagnosis via mergency presentation(eP).earlier diagnoses may be made by Two Week Wait(TWW)referrals through General practitioner(GP).We hypothesise that TWW referrals and eP routes to diagnosis differ across regions in *** To investigate routes to diagnosis of CCA over time,regional variation and influencing *** We linked patient records from the National Cancer Registration Dataset to Hospital episode Statistics,Cancer Waiting Times and Cancer Screening Programme datasets to define routes to diagnosis and certain patient characteristics for patients diagnosed 2006-2017 in *** used linear probability models to investigate geographic variation by assessing the proportions of patients diagnosed via TWW referral or eP across Cancer Alliances in england,adjusting for potential *** between the proportion of people diagnosed by TWW referral and eP was investigated with Spearman’s correlation *** Of 23632 patients diagnosed between 2006-2017 in england,the most common route to diagnosis was eP(49.6%).Non-TWW GP referrals accounted for 20.5%of diagnosis routes,13.8%were diagnosed by TWW referral,and the remainder 16.2%were diagnosed via an‘other’or Unknown *** proportion diagnosed via a TWW referral doubled between 2006-2017 rising from 9.9%to 19.8%,conversely eP diagnosis route declined,falling from 51.3%to 46.0%.Statistically significant variation in both the TWW referral and eP proportions was found across Cancer ***,presence of comorbidity and underlying liver disease were independently associated with both a lowe

关键词： Cholangiocarcinoma Route to diagnosis Two Week Wait emergency presentation Regional variation

Impact of Locus of Control and Job Type on the Perception of Autopsy among Medical and Nonmedical Workers in a Nigerian Tertiary Health Institution

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Journal of Forensic Science and Medicine 2016年第3期2卷 136-140页

作者： Uwom Okereke eze Mfon e Ineme helen O Osinowo Department of Pathology University College Hospital Department of Psychology University of IbadanIbadan1Department of PsychologyUniversity of UyoUyoNigeria

The impact of locus of control and job type on the perception of autopsy among medical and nonmedical workers in University College Hospital,Ibadan,was ***‑two medical and 46 nonmedical workers from the hospital participated in the *** ex post facto design was *** Autopsy Perception Scale and Locus of Control Scale were used as *** t‑test result(t[136]=−2.03;Ped that hospital workers with an internal locus of control reported to have a more positive perception of autopsy than those with an external locus of control;the t‑test result(t[136]=−2.29;Ped that medical workers reported a more positive perception of autopsy than nonmedical ***,the t‑test result(t[136]=−0.82;P>0.05)showed that there was no significant difference between workers who had had an autopsy conducted on their deceased relatives and those who had *** results were discussed in line with existing literature.

关键词： Autopsy hospital workers job type locust of control perception