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Diagnostic and therapeutic potentials of microRNAs in cholangiopathies

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Liver research 2017年第1期1卷 34-41页

作者： Lindsey Kennedy Heather Francis Fanyin Meng Shannon Glaser Gianfranco Alpini research Central Texas Veterans Health Care SystemTempleTXUSA Department of Medicine Texas A&M Health Science CenterCollege of MedicineTempleTXUSA baylor scott&white digestive disease research center Baylor Scott&White HealthTempleTXUSA

Cholangiopathies are a group of rare,devastating diseases that arise from damaged cholangiocytes,the cells that line the intra-and extra-hepatic bile ducts of the biliary *** result in significant morbidity and mortality and are a major cause of liver transplantation.A better understanding of the underlying pathogenesis that influences cholangiocyte dysregulation and cholangiopathy progression is necessary,considering the dismal prognosis associated with these *** are a class of small,non-coding RNAs that regulate post-transcriptional mRNA expression of specific *** role of microRNAs has expanded to include the initiation and development of many diseases,including *** microRNA regulation of cholangiopathies may provide diagnostic and therapeutic benefit for these *** this review,the authors primarily focus on studies published within the last five years that help determine the diagnostic and therapeutic potential of microRNAs in cholangiopathies.

关键词： microRNAs Cholangiopathies Diagnosis Therapy

Cellular crosstalk during cholestatic liver injury

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Liver research 2017年第1期1卷 26-33页

作者： Joanne Thomson Laura Hargrove Lindsey Kennedy Jennifer Demieville Heather Francis research Central Texas Veterans Healthcare SystemTXUSA digestive disease research center Baylor Scott&White HealthTXUSA Medicine Texas A&M Health Science CenterTempleTXUSA

The functions of the liver are very *** detoxifying blood to storing glucose in the form of glycogen and producing bile to facilitate fat digestion,the liver is a very active and important *** liver is comprised of many varied cell types whose functions are equally *** line the biliary tree and aid in transporting and adjusting the composition of bile as it travels to the *** stellate cells and portal fibroblasts are located in different areas within the liver architecture,but both contribute to the development of fibrosis upon activation after liver *** cells,including those that constitute the peribiliary vascular plexus,are involved in functions other than blood delivery to and from the liver,such as supporting the growth of the biliary tree during *** cells are normally found in healthy livers but in very low ***,after injury,mast cell numbers greatly increase as they infiltrate and release factors that exacerbate the fibrotic *** not an all-inclusive list,these cells have individual roles within the liver,but they are also able to communicate with each other by cellular *** this review,we examine some of these pathways that can lead to an increase in the homeostatic dysfunction seen in liver injury.

关键词： Mast cells Paracrine Cholangiocytes Hepatic stellate cells Crosstalk

Functional roles of gut bacteria imbalance in cholangiopathies

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Liver research 2019年第1期3卷 40-45页

作者： Keisaku Sato Fanyin Meng Giammarco Fava Shannon Glaser Gianfranco Alpini Division of research Central Texas Veterans Health Care SystemTempleTXUSA baylor scott&white digestive disease research center Baylor Scott&White Health CareTempleTXUSA Department of Medical Physiology Texas A&M University College of MedicineTempleTXUSA Ospedali Riuniti di Ancona AnconaItaly

Cholangiopathies are caused by bile duct damage or inflammation followed by cholestasis leading to liver *** duct epithelial cells,cholangiocytes,are a primary target for *** reaction is often observed in cholangiopathies and the proliferation of cholangiocytes is associated with ductular reaction and liver *** evidence suggests that patients with chol-angiopathies have different gut bacterial profiles from healthy individuals,indicating the association between gut microbiota and *** acids are produced by hepatocytes and modified by gut *** acids regulate cholangiocyte proliferation but effects vary depending on the type of bile *** studies suggest that therapies targeting gut bacteria,such as antibiotics administration and gut bacteria depletion or therapies using gut bacteria-associated bile acids,such as ursodeoxycholic acid(UDCA)administration,may be useful for treatments of cholangiopathies,although data are contro-versial depending on animal models or *** review summarizes current understandings of functional roles of gut bacterial imbalance and strategies for treatments of cholangiopathies targeting gut bacteria.

关键词： Cholangiopathies Bile acids Gut bacteria Cholangiocytes Cholestasis Inflammation

Biogenic amines serotonin and dopamine regulate cholangiocyte hyperplastic and neoplastic growth

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World Journal of Gastrointestinal Pathophysiology 2010年第2期1卷 63-68页

作者： Gabriel A Frampton Jonathan Ramirez Akimuddin Mohamad Sharon DeMorrow Department of Medicine Texas A&M Health Science CenterCollege of Medicine digestive disease research center Department of MedicineScott and White Hospital

Biogenic amines,such as serotonin and dopamine,regulate a multitude of cellular responses.A great deal of effort has been invested into understanding the effects of these molecules and their corresponding receptor systems on cholangiocyte and cholang-iocarcinoma secretion,apoptosis and *** review summarizes the results of these efforts and highlights the importance of these regulatory molecules on the physiology and pathophysiology of *** we have focused on the recent findings into the effects of serotonin and dopamine on cholangiocyte hyperplasia and neoplastic growth.

关键词： Ductal secretion Cholangiocarcinoma Monoamine oxidase A Tryptophan hydroxylase 1 Tyrosine hydroxylase

Involvement of cholangiocyte proliferation in biliary fibrosis

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World Journal of Gastrointestinal Pathophysiology 2010年第2期1卷 30-37页

作者： Sally Priester Candace Wise Shannon S Glaser Department of Medicine Scott and White and Texas A&M Health Science CenterCollege of Medicine Division of research and Education Scott and White and Texas A&M Health Science CenterCollege of Medicine digestive disease research center Scott and White and Texas A&M Health Science CenterCollege of Medicine

Cholangiocytes are the epithelial cells that line the biliary *** the adult liver,they are a mitotically dormant cell population,unless ductular reaction is triggered by *** ability of cholangiocytes to proliferate is important in many different human pathological liver conditions that target this cell type,which are termed cholangiopathies(*** biliary cirrhosis,primary sclerosing cholangitis and biliary atresia).In our article,we provide background information on the morphological and functional heterogeneity of cholangiocytes,summarize what is currently known about their proliferative processes,and briefly describe the diseases that target these *** addition,we address recent findings that suggest cholangiocyte involvement in epithelial-to-mesenchymal transformation and liver fibrosis,and propose directions for future studies.

关键词： Biliary epithelium Cholangiopathies Cholestasis Integrins Liver fibrosis Proliferation

Varicocele management in the era of in vitro fertilization/intracytoplasmic sperm injection

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Asian Journal of Andrology 2016年第3期18卷 343-348,I0006,I0007页

作者： Piyush Pathak Aravind Chandrashekar Tariq S Hakky Alexander W Pastuszak scott Department of Urology Baylor College of Medicine Houston TX USA scott Department of Urology Kaiser Permanente Riverside Medical Center Riverside CAUSA Advanced Uro ogy At anta GA USA scott Department of Urology Center for Reproductive Medicine Baylor College of Medicine Houston TX USA scott Department of Urology Baylor College of Medicine Houston TxUSA.

Varicocele is the most common surgically treatable cause of male infertility, and often results in alterations in semen parameters, sperm DNA damage, and changes to the seminal milieu. Varicocele repair can result in improvement in these parameters in the majority of men with clinical varicocele; data supporting repair in men with subclinical varicocele are less definitive. In couples seeking fertility using assisted reproductive technologies （ARTs）, varicocele repair may offer improvement in semen parameters and sperm health that can increase the likelihood of successful fertilization using techniques such as in vitro fertilization （IVF） or intracytoplasmic sperm injection （ICSI）, or may decrease the level of ART needed to achieve successful pregnancy. Male infertility is an indicator of general male health, and evaluation of the infertile male with an eye toward future health can facilitate optimal screening and treatment of these men. Furthermore, varicocele may represent a progressive lesion, offering an argument for its repair, although this is currently unclear.

关键词： hypogonadism Leydig cell male fertility Sertoli cell varicocele

The effects of advanced paternal age on fertility

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Asian Journal of Andrology 2013年第6期15卷 723-728,I0005页

作者： Jason R Kovac Josephine Addai Ryan P Smith Robert M Coward Dolores J Lamb Larry I Lipshultz scott Department of Urology Department of Molecular and Cellular Biology The Center for Reproductive Medicine Baylor College of Medicine Houston TX 77030 USA

Modern societal pressures and expectations over the past several decades have resulted in the tendency for couples to delay conception. While women experience a notable decrease in oocyte production in their late thirties, the effect of age on spermatogenesis is less well described. While there are no known limits to the age at which men can father children, the effects of advanced paternal age are incompletely understood. This review summarizes the current state of knowledge regarding advanced paternal age and its implications on semen quality, reproductive success and offspring health. This review will serve as a guide to physicians in counseling men about the decision to delay paternity and the risks involved with conception later in life.

关键词： aging male fertility outcomes male infertility paternal age

The varicocele： diagnostic dilemmas, therapeutic challenges and future perspectives

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Asian Journal of Andrology 2016年第2期18卷 276-281,J0007页

作者： Koji Chiba Ranjith Ramasamy Dolores J Lamb Larry I Lipshultz center for Reproductive Medicine Baylor College of Medicine Houston TX USA scott Department of Urology Baylor College of Medicine Houston TX USA Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX USA.

A varicocele is defined as the abnormal dilation of the internal testicular vein and pampiniform venus plexus within the spermatic cord. If a semen analysis is not obtained from the adolescent male, in the absence of other symptoms, the main clinical indication used by many urologists to recommend repair is testicular atrophy. The varicocele may result in testicular damage in some males causing testicular atrophy with impaired sperm production and decreased Leydig cell function, while in other males the varicocele may seemingly cause no ill effects. In adult men, varicoceles are frequently present and surgically correctable, yet the measurable benefits of surgical repair are slight according to a Cochrane review. While occurring more commonly in infertile men than fertile men, only 20% of men with a documented varicocele will suffer from fertility problems. Most varicoceles found in adolescents are detected during a routine medical examination, and it is difficult to predict which adolescent presenting with a varicocele will ultimately show diminished testicular function in adolescence or adulthood. As in adults, the mainstay of treatment for varicocele in adolescents is surgical correction. However, unlike an adult varicocelectomy （the microsurgical approach is the most common）, treatment for an adolescent varicocele is more often laparoscopic. Nevertheless, the goals of treatment are the same in the adolescent and adult patients. Controversy remains as to which patients to treat, when to initiate the treatment, and what type of treatment is the best. This review will present the current understanding of the etiology, diagnosis and treatment of the adolescent varicocele.

关键词： adolescent adult management varicocele

Maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in adult male and female mouse offspring

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Neural Regeneration research 2023年第11期18卷 2443-2448页

作者： McCoy Clementson Lauren Hurley Sarah Coonrod Calli Bennett Purvaja Marella Agnes S.Pascual Kasey Pull Brandi Wasek Teodoro Bottiglieri Olga Malysheva Marie A.Caudill Nafisa M.Jadavji Department of Biomedical Sciences Midwestern UniversityGlendaleAZUSA College of Osteopathic Medicine Midwestern UniversityGlendaleAZUSA College of Veterinary Medicine Midwestern UniversityGlendaleAZUSA center of Metabolomics Institute of Metabolic DiseaseBaylor Scott&White Research InstituteDallasTXUSA Division of Nutritional Sciences Cornell UniversityIthacaNYUSA Department of Neuroscience Carleton UniversityOttawaONCanada Department of Child Health College of Medicine–PhoenixUniversity of ArizonaPhoenixAZUSA

Maternal one-carbon metabolism plays an important role in early life *** is a well-established connection between the fetal environment and the health status of the *** r,there is a knowledge gap on how maternal nutrition impacts stro ke outcomes in *** aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcomes in 3-month-old *** female mice were fed a folic acid-deficient diet,choline-deficient diet,or control diet 4 weeks before *** we re continued on diets during pregnancy and la *** and female offspring were weaned onto a control diet and at 2 months of age were subjected to ischemic stroke within the sensorimotor cortex via photothrombotic *** maintained on either a folic acid-deficient diet or choline-deficient diet had reduced levels of S-adenosylm ethionine in the liver and S-adenosylhomocysteine in the *** ischemic stro ke,motor function was impaired in 3-month-old offspring from mothers receiving either a folic acid-deficient diet or choline-deficient diet compared to the animals receiving a control *** brain tissue,there was no difference in ischemic damage *** protein levels were assessed in ischemic brain tissue,there were lower levels of active caspase-3 and hypoxia-inducible factor 1α in males compared to females and betaine levels were reduced in offspring from the mothers receiving a choline-deficient *** results demonstrate that a deficient maternal diet at critical time points in neurodevelopment results in worse stro ke *** study emphasizes the importance of maternal diet and the impact it can have on offspring health.

关键词： apoptosis choline metabolism folic acid ischemic stroke maternal diet motor function one-carbon metabolism stroke outcome