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Epididymis-specific lipocalin promoters

Asian Journal of Andrology 2007年第4期9卷 515-521页

作者： Kichiya Suzuki Xiuping Yu Pierre Chaurand Yoshihiko Araki Jean-Jacques Lareyre Richard M. Caprioli Marie-Claire Orgebin-Crist Robert J. Matusik Department of Obstetrics and Gynecology Tohoku University Graduate School of Medicine Sendai 980-8574 Japan departments of Urologic Surgery Vanderbilt University School of Medicine Nashville Tennessee 37232 USA departments of Biochemistry Vanderbilt University School of Medicine Nashville Tennessee 37232 USA departments of Obstetrics and Gynecology Vanderbilt University School of Medicine Nashville Tennessee 37232 USA departments of Cell and Developmental Biology Vanderbilt University School of Medicine Nashville Tennessee 37232 USA departments of Mass Spectrometry Research Center and Vanderbilt University School of Medicine Nashville Tennessee 37232 USA departments of Center for Reproductive Biology Research Vanderbilt University School of Medicine Nashville Tennessee 37232 USA

Our goal is to decipher which DNA sequences are required for tissue-specific expression of epididymal genes. At least 6 epididymis-specific lipocalin genes are known. These are differently regulated and regionalized in the epididymis. Lipocalin 5 （Lcn5 or mE-RABP） and Lipocalin 8 （Lcn8 or mEP17） are homologous genes belonging to the epididymis-specific lipocalin gene cluster. Both the 5 kb promoter fragment of the Lcn5 gene and the 5.3 kb promoter fragment of the Lcn8 gene can direct transgene expression in the epididymis （Lcn5 to the distal caput and Lcn8 to the initial segment）, indicating that these promoter fragments contain important cis-regulatory element（s） for epididymisspecific gene expression. To define further the fragments regulating gene expression, the Lcn5 promoter was examined in transgenic mice and immortalized epididymal cell lines. After serial deletion, the 1.8 kb promoter fragment of the Lcn5 gene was sufficient for tissue-specific and region-specific gene expression in transgenic mice. Transient transfection analysis revealed that a transcription factor forkhead box A2 （Foxa2） interacts with androgen receptor and binds to the 100 bp fragment of the Lcn5 promoter between 1.2 kb and 1.3 kb and that Foxa2 expression inhibits androgen-dependent induction of the Lcn5 promoter activity. Immunohistochemistry indicated a restricted expression of Foxa2 in the epididymis where endogenous Lcn5 gene expression is suppressed and that the Foxa2 inhibition of the Lcn5 promoter is consistent with the lack of expression of Lcn5 in the corpus and cauda. Our approach provides a basic strategy for further analysis of the epididymal lipocalin gene regulation and flexible control of epididymal function. （Asian J Androl 2007 July; 9： 515-521）

关键词： androgen epididymis gene cluster gene evolution gene regulation lipocalin transcription factor

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Denosumab in bone-metastatic prostate cancer： known effects on skeletal＇related events but unknown effects on quality of life

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Asian Journal of Andrology 2011年第4期13卷 612-613页

作者： Oliver Sartor departments of medicine and Urology Tulane University School of Medicine New Orleans LA USA

The purpose of new pharmaceuticals is to improve how patients feel, function or survive. Exceptions exist when surrogates are developed and we know that those surrogates correlate well with one of the above. Hypercholesterolemia is a well-accepted example. We know that high cholesterol is a reasonable indicator that results in increased risk of strokes and heart attacks. Thus, we treat hypercholesterolemia in hopes that our patients＇ health will improve.

关键词： new pharmaceuticals skeletal-related

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Osteocyte Egln1/Phd2 links oxygen sensing and biomineralization via FGF23

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Bone Research 2023年第1期11卷 178-192页

作者： Megan L.Noonan Pu Ni Emmanuel Solis Yamil G.Marambio Rafiou Agoro Xiaona Chu Yue Wang Hongyu Gao Xiaoling Xuei Erica L.Clinkenbeard Guanglong Jiang Sheng Liu Steve Stegen Geert Carmeliet William R.Thompson Yunlong Liu Jun Wan Kenneth E.White Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN46202USA Laboratory of Clinical and Experimental Endocrinology Department of Chronic Diseases and MetabolismKU Leuven3000LeuvenBelgium Department of Physical Therapy Indiana University School of MedicineIndianapolisIN46202USA Department of Anatomy Cell Biologyand PhysiologyIndiana University School of MedicineIndianapolisIN46202USA Center for Computational Biology and Bioinformatics Indiana University School of MedicineIndianapolisIN46202USA departments of medicine/Division of Nephrology Indiana University School of MedicineIndianapolisIN46202USA

Osteocytes act within a hypoxic environment to control key steps in bone ***23,a critical phosphate-regulating hormone,is stimulated by low oxygen/iron in acute and chronic diseases,however the molecular mechanisms directing this process remain *** goal was to identify the osteocyte factors responsible for FGF23 production driven by changes in oxygen/iron ***-inducible factor-prolyl hydroxylase inhibitors(HIF-PHI)which stabilize HIF transcription factors,increased Fgf23 in normal mice,as well as in osteocyte-like cells;in mice with conditional osteocyte Fgf23 deletion,circulating i FGF23 was *** inducible MSC cell line(‘MPC2’)underwent FG-4592 treatment and ATACseq/RNAseq,and demonstrated that differentiated osteocytes significantly increased HIF genomic accessibility versus progenitor *** genomics also revealed increased prolyl hydroxylase Egln1(Phd2)chromatin accessibility and expression,which was positively associated with osteocyte *** mice with chronic kidney disease(CKD),Phd1-3 enzymes were suppressed,consistent with FGF23 upregulation in this *** loss of Phd2 from osteocytes in vivo resulted in upregulated Fgf23,in line with our findings that the MPC2 cell line lacking Phd2(CRISPR Phd2-KO cells)constitutively activated Fgf23 that was abolished by HIF1α*** vitro,Phd2-KO cells lost iron-mediated suppression of Fgf23 and this activity was not compensated for by Phd1 *** sum,osteocytes become adapted to oxygen/iron sensing during differentiation and are directly sensitive to bioavailable ***,Phd2 is a critical mediator of osteocyte FGF23 production,thus our collective studies may provide new therapeutic targets for skeletal diseases involving disturbed oxygen/iron sensing.

关键词： FGF23 collective adapted

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Considerations on Research Priorities in Physical and Rehabilitation medicine

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中国康复医学杂志 2009年第11期24卷 961-966页

作者： Walter R. Frontera departments of Physical medicine and Rehabilitation and Physiology

Significant attention has been given recently to thetopic of research in the field of Physical and Rehabilitationmedicine (PRM) in professional organizations, national

关键词：康复医学医学研究医疗卫生行业物理治疗

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Effects of Chinese Herbal medicine Combined with He-Ne Laser on Lipoperoxide and Superoxide Dismutase in Chloasma Patients

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Journal of Traditional Chinese medicine 2009年第3期29卷 163-166页

作者：吴艳华李其林杨秀文陈正秋 departments of Chinese medicine and Dermatology Guangzhou Red Cross Hospital

Objective: To observe the effects of Chinese decoction and ligustrazin hydrochloride injection combined with He-Ne laser on lipoperoxide (LPO) and Superoxide dismutase (SOD) in patients with chloasma. Methods: 90 cases of chloasma were randomly divided into the following two groups: a treatment group (of 54 cases) treated by a self-prepared prescription for toning the kidneys and relieving the depressed liver to remove blood stasis, ligustrazin hydrochloricde injection and He-Ne laser therapy, and a control group (of 36 cases) treated with oral administration of Vitamin E and Vitamin C plus external application of 20% Azelaic acid cream. Results: The total effective rate in the treatment group was 79.6%, which was significantly higher than that of the control group (P<0.05). After treatment, the LPO level in the treatment group was significantly lowered (P<0.01), and the SOD level was significantly elevated (P<0.05). Conclusion: The therapeutic methods adopted in the treatment group may show the action of antioxidation, providing good clinical effects for treating chloasma.

关键词：超氧化物歧化酶激光治疗过氧化脂质黄褐斑氦氖盐酸川芎嗪中药抗氧化作用

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Axonal regeneration after spinal cord injury in zebrafish and mammals: differences, similarities, translation

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Neuroscience Bulletin 2013年第4期29卷 402-410页

作者： Katarina Vajn Jeffery A Plunkett Alexis Tapanes-Castillo Martin oudega departments of Physical medicine & Rehabilitation University of Pittsburgh School of Science Technology and Engineering Management St. Thomas University departments of Neurobiology University of Pittsburgh departments of Bioengineering University of Pittsburgh

Spinal cord injury （SCl） in mammals results in functional deficits that are mostly permanent due in part to the inability of severed axons to regenerate. Several types of growth-inhibitory molecules expressed at the injury site contribute to this regeneration failure. The responses of axons to these inhibitors vary greatly within and between organisms, reflecting axons＇ characteristic intrinsic propensity for regeneration. In the zebrafish （Danio rerio） many but not all axons exhibit successful regeneration after SCI. This review presents and compares the intrinsic and extrinsic determinants of axonal regeneration in the injured spinal cord in mammals and zebrafish. A better understanding of the molecules and molecular pathways underlying the remarkable individualism among neurons in mature zebrafish may support the development of therapies for SCI and their translation to the clinic.

关键词： spinal cord injury axonal regeneration growth inhibition functional recovery zebrafish

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Effect of arteriosclerotic intracranial arterial vessel wall enhancement on downstream collateral flow

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Chinese Medical Journal 2023年第18期136卷 2221-2228页

作者： Liqun Yan Jin Yan Zhenchang Wang Guoshi Wang Zhenzhong Li Yaping Hou Boyuan Huang Qianbo Dong Xiaodan Mu Wei Cao Pengfei Zhao Department of Radiology Beijing Friendship Hospital of Capital Medical UniversityBeijing 100050China departments of Medical Imaging Second Hospital of Hebei Medical UniversityShijiazhuangHebei 050004China Department of Clinical medicine Tianjin Medical UniversityTianjin 300203China departments of Neurology Second Hospital of Hebei Medical UniversityShijiazhuangHebei 050004China Hebei Province Blood Center ShijiazhuangHebei 050000China

Background:The effect of arteriosclerotic intracranial arterial vessel wall enhancement(IAVWE)on downstream collateral flow found in vessel wall imaging(VWI)is not *** of the mechanism underlying IAVWE on VWI,damage to the patient’s nervous system caused by IAVWE is likely achieved by affecting downstream cerebral blood *** present study aimed to investigate the effect of arteriosclerotic IAVWE on downstream collateral ***:The present study recruited 63 consecutive patients at the Second Hospital of Hebei Medical University from January 2021 to November 2021 with underlying atherosclerotic diseases and unilateral middle cerebral artery(MCA)M1-segment stenosis who underwent an magnetic resonance scan within 3 days of symptom *** patients were divided into 4 groups according to IAVWE and the stenosis ratio(Group 1,n=17;Group 2,n=19;Group 3,n=13;Group 4,n=14),and downstream collateral flow was analyzed using three-dimensional pseudocontinuous arterial spin labeling(3D-pCASL)and RAPID *** National Institutes of Health Stroke Scale(NIHSS)scores of the patients were also ***-factor multivariate analysis of variance using Pillai’s trace was used as the main statistical ***:No statistically significant difference was found in baseline demographic characteristics among the ***,but not the stenosis ratio,had a statistically significant significance on the late-arriving retrograde flow proportion(LARFP),hypoperfusion intensity ratio(HIR),and NIHSS scores(F=20.941,P<0.001,Pillai’s trace statistic=0.567).The between-subject effects test showed that IAVWE had a significant effect on the three dependent variables:LARFP(R^(2)=0.088,F=10.899,P=0.002),HIR(R^(2)=0.234,F=29.354,P<0.001),and NIHSS(R^(2)=114.339,F=33.338,P<0.001).Conclusions:Arteriosclerotic IAVWE significantly reduced downstream collateral flow and affected relevant neurological *** was an independent factor affecting downstream collateral fl

关键词： Intracranial arterial vessel wall enhancement Arteriosclerosis Stroke Cerebral collateral flow Three-dimensional pseudo-continuous arterial spin-labeling Magnetic Resonance Imaging

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Ryanodine receptors as pharmacological targets for heart disease

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Acta Pharmacologica Sinica 2007年第7期28卷 937-944页

作者： Marco SANTONASTAS Xander H T WEHRENS departments of Molecular Physiology and Biophysics departments of Molecular Physiology and Biophysics and Medieine(Cardiology) Baylor College of MedicineHoustonTexas 77030USA

Calcium release from intracellular stores plays an important role in the regulationof muscle contraction and electrical signals that determine the heart *** receptor （RyR） is the major calcium (Ca2+) release channel required forexcitation-contraction coupling in the *** studies have demonstratedthat RyR are macromolecular complexes comprising of 4 pore-forming channelsubunits,each of which is associated with regulatory *** andexperimental studies over the past 5 years have provided compelling evidencethat intracellular Ca2+release channels play a pivotal role in the development ofcardiac arrhythmias and heart *** in the channel regulation andsubunit composition are believed to cause diastolic calcium leakage from thesarcoplasmic reticulum,which could trigger arrhythmias and weaken ***,cardiac RyR have emerged as potential therapeutic tar-gets for the treatment of heart ***,there is a strong desire toidentify and/or develop novel pharmacological agents that may target these Ca2+signaling *** agents known to modulate RyR in the heart,and their potential application towards the treatment of heart disease are dis-cussed in this review.

关键词： arrhythmias calcium release channel heart failure pharmacology ryanodine receptor

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Implications of the prostate intervention versus observation trial （PIVOT）

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Asian Journal of Andrology 2012年第6期14卷 803-804页

作者： Oliver Sartor departments of medicine and Urology Tulane University School of Medicine New Orleans LA 70112 USA

PSA screening improves early detection of prostate cancer but can lead to overtreatment if all of these cancers are treated. The first randomized treatment study for men with PSA detected cancers has now been reported.

关键词： RADICAL PROSTATECTOMY CANCER

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Body mass index and COVID-19 outcomes:A retrospective cross-sectional study at a tertiary care center in India

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Journal of Acute Disease 2022年第2期11卷 71-76页

作者： Hardeva Ram Nehara Sahdev Kumawat Rohitash Kularia J Amareshwara Prashant Kumar Batar Vivek Goudgaon departments of 1Endocrinology SP Medical CollegeBikanerIndia departments of medicine SP Medical CollegeBikanerIndia

Objective:To determine the association between body weight and COVID-19 ***:This is a retrospective cohort study of COVID-19 patients admitted in a dedicated COVID-19 hospital,a tertiary health care center,between May and June *** data and baseline variables,including age,sex,body mass index(BMI),and comorbidities were ***(death or mechanical ventilation)of the patients with different BMI,age,comorbidities,and qSOFA scores were ***,the risk factors for death or mechanical ventilation were ***:The mean age of the subjects was(51.8±14.7)years old,and 233(74.2%)were *** were 103(32.8%)patients with normal weight,143(45.5%)patients were overweight,and 68(21.7%)patients were ***-hospital deaths and need of mechanical ventilations were significantly higher in the obese and the overweight group compared to the normal weight group,in age group≥65 years compared to<65 years,in patients with≥1 comorbidities compared to patients without comorbidities,in patients with qSOFA scores≥2 compared to patients with qSOFA scores<*** was a significantly increased risk of death(RR:4.1,95%CI 1.0-17.4,P=0.04)and significantly increased need of mechanical ventilation(RR:5.2,95%CI 1.8-15.2,P=0.002)in the obese patients compared with those with normal weight after controlling other ***:Obesity is one of the significant risk factors for adverse outcomes in COVID-19 patients and should be considered during management.

关键词： Overweight Obesity Body mass index COVID-19 Outcome

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