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claudin-11 and occludin are major contributors to Sertoli cell tight junction function, in vitro

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Asian Journal of Andrology 2016年第4期18卷 620-626页

作者： Mark J Mccabe caroline FH Foo Marcel e Dinger peter M Smooker peter G Stanton Male Fertility Regulation Laboratory Hudson Institute of Medical Research Monash Medical Centre Clayton Victoria 3168 Australia School of Applied Sciences Royal Melbourne Institute of Technology University Bundoora Victoria 3088 Australia Kinghorn centre for clinical Genomics Garvan Institute of Medical Research Darlinghurst New South Wales 2010 Australia St Vincent's clinical School UNSW Sydney New South Wales 2052 Australia.

The Sertoli cell tight junction （T J） is the key component of the blood-testis barrier, where it sequesters developing germ cells undergoing spermatogenesis within the seminiferous tubules. Hormonally regulated claudin-11 is a critical transmembrane protein involved in barrier function and its murine knockout results in infertility. We aimed to assess quantitatively the significance of the contribution of claudin-11 to TJ function, in vitro, using siRNA-mediated gene silencing. We also conducted an analysis of the contribution of occludin, another intrinsic transmembrane protein of the TJ. Silencing of claudin-11 and/or occludin was conducted using siRNA in an immature rat Sertoli cell culture model. Transepithelial electrical resistance was used to assess quantitatively TJ function throughout the culture. Two days after siRNA treatment, cells were fixed for immunocytochemical localization of junction proteins or lyzed for RT-PcR assessment of mRNA expression. Silencing of claudin-11, occludin, or both resulted in significant decreases in TJ function of 55% （P 〈 0.01）, 51% （P 〈 0.01）, and 62% （P 〈 0.01）, respectively. Data were concomitant with significant decreases in mRNA expression and marked reductions in the localization of targeted proteins to the Sertoli cell TJ. We provide quantitative evidence that claudin-11 contributes significantly （P 〈 0.01） to Sertoli cell TJ function in vitro. Interestingly, occludin, which is hormonally regulated but not implicated in infertility until late adulthood, is also a significant （P 〈 0.01） contributor to barrier function. Our data are consistent with in vivo studies that clearly demonstrate a role for these proteins in maintaining normal TJ barrier structure and function.

关键词： blood-testis barrier claudin-11 occludin Sertoli cell tight junction siRNA

Trans-synaptic degeneration as a mechanism of neurodegeneration in multiple sclerosis

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Neural Regeneration Research 2023年第12期18卷 2682-2684页

作者： Olwen c.Murphy peter A.calabresi Shiv Saidha Division of Neuroimmunology and Neurological Infections Department of NeurologyJohns Hopkins UniversityBaltimoreMDUSA

Multiple sclerosis(MS) is regarded as an immunemediated,demyelinating disorder of the central nervous system,however neuroaxonal degeneration is accepted as the principal substrate of disability accumulation(Dutta and... 详细信息

关键词： degeneration sclerosis myelin

On environmental threats to male infertility

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Asian Journal of Andrology 2013年第2期15卷 199-200,I0005页

作者： Allen J Wilcox Jens peter e Bonde epidemiology Branch National Institute of Environmental Health Sciences Durham NC 27709-2233 USA Department of Occupational and environmental Medicine University Hospital of Copenhagen Copenhagen NV DK-2400 Denmark

The possibility that environmental pollutants damage human fertility is a topic of both public concern and scientific interest. The effect of environmental factors on male fertility （semen parameters） has been a special focus, stimulated in part by the dramatic damage inflicted by the pcstlcide DBcP on testicular function. extensive searches for testicular toxicants （in particular, the proposed effects of endocrine-disrupting compounds through fetal exposure） have produced little hard evidence of impairment in humans. This scarcity of evidence may reflect the difficultles of studying human fertility. Future fertifity studies should consider the wide spectrum of environmental exposures that plausibly affect reproduction.

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Relationship between apoptotic markers in semen from fertile men and demographic, hormonal and seminal characteristics

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Asian Journal of Andrology 2012年第6期14卷 890-896页

作者： Ina O Specht Marcello Spano Karin S Hougaard Gian c Manicardi Davide Bizzaro Gunnar Toft Aleksander Giwercman Jens-peter e Bonde Department of Occupational and environmental Medicine University Hospital of Copenhagen Copenhagen NV DK-2400 Denmark Laboratory of Toxicology Unit of Radiation Biology and Human Health ENEA Casaccia Research Center Rome 1-00123 Italy National Research centre for the Working environment Copenhagen 0 DK-2100 Denmark Dipartimento di Scienze Agrarie e degli Alimenti Universita di Modena e Reggio Emilia Reggio Emilia 1-42121 Italy Department of Life and environmental Sciences Polytechnic University of Marche Ancona 1-60131 Italy epartment of Occupational Medicine Aarhus University Hospital Aarhus C DK-8000 Denmark Reproductive Medicine centre Maim6 University Hospital Lund University MalmO SE-20502 Sweden

Apoptosis in the testis has two putative roles during normal spermatogenesis; limitation of the germ cell population to numbers that can be supported by the Sertoli cells, and, possibly, selective depletion of meiotic and postmeiotic abnormal germ cells. We investigated the demographic and biological correlates of the pro-apoptotic marker Fas and the anti-apoptotic marker Bcl-xL in sperm cells of fertile men. Six hundred and four men from Greenland, Poland and Ukraine were consecutively enrolled during their pregnant wife＇s antenatal visits. Semen analysis was performed as recommended by the World Health Organization. Immunofluorescence coupled to flow cytometry was utilized for detection of apoptotic markers in the sperm cell. DNA damage was assessed by flow cytometry using both the sperm chromatin structure assay （ScSA） and the terminal deoxynucleotidyl transferase dUTP nick end labelling （TUNeL） assay. The percentage of Fas-positive sperm cells was higher in men with high total sperm count （P〈O.01）, more motile sperms （P=-O.04） and fewer sperm head defects （P=-O.05）. These associations were consistent within and across study regions. Furthermore, testosterone, follicle-stimulating hormone （FSH） and sexual hormone-binding globulin （SHBG） were significantly negatively correlated with Fas within and across regions as well. The data indicated no association between the anti-apoptotic Bcl-xL marker and semen or personal characteristics. The finding of Fas-positive sperm cells associated with better semen quality in a cohort of spouses of pregnant women seems different from previous data obtained in infertile men and warrants further investigation to clarify the biological significance of sperm apoptotic markers.

关键词： apoptosis Bcl-x protein Fas-associated death domain protein fertility sperm chromatin structure assay (ScSA) sper- matozoa TUN eL assay

effect of restricted feeding on hen performance,egg quality and organ characteristics of individual laying hens

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Animal Nutrition 2023年第3期14卷 141-151页

作者： Doreen O.Anene Yeasmin Akter peter c.Thomson peter Groves cormac J.O'Shea Department of Animal Science School of BiosciencesUniversity of NottinghamLoughboroughLE125RDUnited Kingdom School of Life and environmental Sciences Faculty of ScienceUniversity of SydneyCamdenNSW 2570Australia Sydney School of Veterinary Science Faculty of SciencePoultry Research FoundationUniversity of SydneyCamdenNSW 2570Australia Department of Bioveterinary and Microbial Sciences Technological University of the Shannon:Midlands MidwestDublin RoadAthloneCo WestmeathN37 HD68Ireland

This study was to assess the impact of permanent or temporary restricted feeding on laying hen production traits,physiology,and egg *** hundred and forty individually housed ISA Brown hens were monitored across 2 phases,assigned to 3 treatments:ad libitum feeding(ALF),temporary restricted feeding(TRF)and permanent restricted feeding(PRF),n=80 hens per *** Phase 1(P1),22 to40 weeks,the TRF and PRF hens were offered 115 g of feed *** Phase 2(P2),41 to 46 weeks,the TRF hens were transitioned to ALF status while the ALF and PRF hens remained as in *** 35 to 40 weeks,eggs were collected once weekly from 15 hens per treatment and assessed for differences in albumen,yolk,and shell *** 45 weeks,10 hens each from the ALF and PRF groups were euthanized and differences in organ characteristics were *** P1,feed intake,feed to egg conversion ratio and body weight(BW)change were lower(Pe albumen height and Haugh unit were higher(Pen treatments compared to hens allocated the ALF *** P2,TRF and ALF hens had a higher egg production and egg mass than PRF(Peight change in P2 was higher in TRF and similar in both ALF and PRF,while feed intake and feed conversion ratio were higher in TRF followed by ALF and least in the PRF treatment group(Peeks ALF hens had a greater abdominal fat pad weight and fatty liver haemorrhagic syndrome lesion score compared to *** hens to 115 g of feed per day from point of lay restrained BW,improved feed conversion ratio and albumen quality and reduced abdominal fat pad deposition and clinical signs of fatty liver haemorrhagic syndrome in individually housed laying hens.

关键词： Restricted feeding Albumen quality Fatty liver haemorrhagic syndrome Abdominal fat Laying hen Body weight

Management of locally advanced and metastatic colon cancer in elderly patients

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World Journal of Gastroenterology 2014年第8期20卷 1910-1922页

作者： peter c Kurniali Borys Hrinczenko Anas Al-Janadi Division of Hematology/Oncology Michigan State UniversityMi 48910United States

colon cancer is the second leading cause of cancer mortality in the United States with a median age at diagnosis of 69 years. Sixty percent are diagnosed over the age of 65 years and 36% are 75 years or older. At diagnosis, approximately 58% of patients will have locally advanced and metastatic disease, for which systemic chemotherapy has been shown to improve survival. Treatment of cancer in elderly patients is more challenging due to multiple factors, including disabling co-morbidities as well as a decline in organ function. cancer treatment of elderly patients is often associated with more toxicities that may lead to frequent hospitalizations. In locally advanced disease, fewer older patients receive adjuvant chemotherapy despite survival benefit and similar toxicity when compared to their younger counterparts. A survival benefit is also observed in the palliative chemotherapy setting for elderly patients with metastatic disease. When treating elderly patients with colon cancer, one has to consider drug pharmacokinetics and pharmacodynamics. Since chronological age is a poor marker of a patient’s functional status, several methods of functional assessment including performance status and activities of daily living (ADL) or instrumental ADL, or even a comprehensive geriatric assessment, may be used. There is no ideal chemotherapy regimen that fits all elderly patients and so a regimen needs to be tailored for each individual. Important considerations when treating elderly patients include convenience and tolerability. This review will discuss approaches to the management of elderly patients with locally advanced and metastatic colon cancer.

关键词： colon cancer elderly chemotherapy Management Toxicity

Invariant Measures for Nonlinear conservation Laws Driven by Stochastic Forcing

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chinese Annals of Mathematics,Series B 2019年第6期40卷 967-1004页

作者： Gui-Qiang G.cHeN peter H.c.PANG Mathematical Institute University of Oxford

Some recent developments in the analysis of long-time behaviors of stochastic solutions of nonlinear conservation laws driven by stochastic forcing are *** existence and uniqueness of invariant measures are established for anisotropic degenerate parabolic-hyperbolic conservation laws of second-order driven by white *** further developments,problems,and challenges in this direction are also discussed.

关键词： Stochastic solutions entropy solutions Invariant measures existence Uniqueness Stochastic forcing Anisotropic degenerate Parabolichyperbolic equations Long-time behavior

Hepatotoxicity of NONI juice: Report of two cases

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World Journal of Gastroenterology 2005年第30期11卷 4758-4760页

作者： Vanessa Stadlbauer peter Fickert carolin Lackner Jutta Schmerlaib peter Krisper Michael Trauner Rudolf e Stauber Department of Internal Medicine Institute of Pathology

NONI juice (Morinda citrifolia) is an increasingly popular wellness drink claimed to be beneficial for many *** overt toxicity has been reported to date. We present two cases of novel hepatotoxicity of NONI juice. causality of liver injury by NONI juice was asses-sed. Routine laboratory tests and transjugular or percutaneous liver biopsy were performed. The first patient underwent successful liver transplantation while the second patient recovered spontaneously after cessation of NONI juice.A 29-year-old man with previous toxic hepatitis associated with small doses of paracetamol developed sub-acute hepatic failure following consumption of 1.5 L NONI juice over 3 wk necessitating urgent liver transplantation. A 62-year-old woman without evidence of previous liver disease developed an episode of self-limited acutehepatitis following consumption of 2 L NONI juice for over 3 mo. The most likely hepatotoxic components of Morinda citrifolia were anthraquinones. Physicians should be aware of potential hepatotoxicity of NONI juice.

关键词： Herbal hepatotoxicity Drug-induced hepatitis NONI juice Acute liver failure

Small bowel MRI enteroclysis or follow through:Which is optimal?

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World Journal of Gastroenterology 2009年第42期15卷 5300-5306页

作者： Ian c Lawrance christopher J Welman peter Shipman Kevin Murray School of Medicine and Pharmacology University of Western AustraliaFremantle HospitalWA 6160Australia centre for Inflammatory Bowel Disease Fremantle HospitalWA 6160Australia Department of Radiology Fremantle HospitalWA 6160Australia Statistical consulting Group School of Mathe-matics and StatisticsUniversity of Western AustraliaWA 6009Australia

AIM： TO determine if a nasojejunal tube （NJT） is required for optimal examination of enteroclysis and if patients can be examined only in the supine position. MeTHODS： Data were collected from all patients undergoing small bowel （SB） magnetic resonance imaging （MRI） examination over a 32-mo period. Patients either underwent a magnetic resonance （MR） follow-through （MRFT） or a MR enteroclysis （MRe） in the supine position. The quality of proximal and distal SB distension as well as the presence of motion artefact and image quality were assessed by 2 radiologists. ReSULTS： One hundred and fourteen MR studies were undertaken （MRFT-49, MRe-65） in 108 patients in the supine position only. Image artefact was more frequent in MRe than in MRFT （29.2% vs 18.4%）, but was not statistically significant （P = 0.30）. Adequate distension of the distal SB was obtained in 97.8% of MRFT examinations and in 95.4% of MRe examinations, respectively. Proximal SB distension was, however, less frequently optimal in MRFT than in MRe （P = 0.0036）, particularly in patients over the age of 50 years （P = 0.0099）. Image quality was good in all examinations. cONcLUSION： All patients could be successfully iraaged in the supine position. MRe and MRFT are equivalent for distal SB distension and artefact effects. Proximal SB distension is frequently less optimal in MRFT than in MRe. MRe is, therefore, the preferred MR examination method of the SB.

关键词： Magnetic resonance enteroclysis Magnetic resonance enterography Magnetic resonance follow through Artefact