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Differentiation of human embryonic stem cells derived mesenchymal stem cells into corneal epithelial cells after being seeded on decellularized SMILE-derived lenticules

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International Journal of Ophthalmology(English edition) 2019年第5期12卷 717-724页

作者： Yao Chen Ye-Wei Yin Yang Zhao Xiao-Ying Wu Kelly Young Wei-Tao Song Xiao-Bo Xia Dan Wen Department of Ophthalmology Xiangya HospitalCentral South University Department of veterans Affairs Miami VA Healthcare System

AIM: To evaluate the feasibility of mesenchymal stem cells(MSCs) to differentiate into corneal epithelial cells after being seeded on the decellularized small incision lenticule extraction(SMILE)-derived lenticules. METHODS: The fresh lenticules procured from patients undergoing SMILE for the correction of myopia were decellularized. The MSCs were subsequently cultivated on those denuded lenticules. The MSCs without lenticules were used as a control. The proliferation activity of the MSCs after seeding 24 h was quantitatively determined with the Cell Counting Kit-8(CCK-8) assay. Immunofluorescence staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR) were used to assess the marker expression in differentiated MSCs. RESULTS: The data showed that both fresh and decellularized lenticules could significantly promote the proliferation of MSCs, compared to that in control(P=0.02 for fresh lenticules, P=0.001 for decellularize ones, respectively). The MSCs seeded on both lenticules were positive for cytokeratin 3(CK3) staining. The expression of CK3 increased 5-fold in MSCs seeded on fresh lenticules and 18-fold on decellularized ones, compared to that in control. There was a significant difference in the expression of CK3 in MSCs seeded on fresh and decellularized lenticules(P0.05), while the expression of these markers was decreased in MSCs seeded on decellularized ones. CONCLUSION: These results suggest that the decellularized lenticules might be more suitable for MSCs to differentiate into corneal epithelial cells, which offersthe prospect of a novel therapeutic modality of SMILEderived lenticules in regenerative corneal engineering.

关键词： mesenchymal stem cells small incision lenticule extraction lenticules decellularization corneal epithelial cells

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Bile acid signaling and biliary functions

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Acta Pharmaceutica Sinica B 2015年第2期5卷 123-128页

作者： Hannah Jones Gianfranco Alpini Heather Francis Baylor Scott & White Digestive Disease Research Center Division Research Central Texas Veterans Health Care System Department of Medicine Texas A&M University

This review focuses on various components of bile acid signaling in relation to cholangiocytes. Their roles as targets for potential therapies for cholangiopathies are also explored. While many factors are involved in these complex signaling pathways, this review emphasizes the roles of transmembrane G protein coupled receptor(TGR5), farnesoid X receptor(FXR), ursodeoxycholic acid(UDCA) and the bicarbonate umbrella. Following a general background on cholangiocytes and bile acids,we will expand the review and include sections that are most recently known(within 5–7 years) regarding the field of bile acid signaling and cholangiocyte function. These findings all demonstrate that bile acids influence biliary functions which can, in turn, regulate the cholangiocyte response during pathological events.

关键词： Bile acids Cholangiocytes Receptors Signaling

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Quetiapine augmentation of prolonged exposure therapy in veterans with PTSD and a history of mild traumatic brain injury: design and methodology of a pilot study

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Military Medical Research 2021年第1期8卷 121-131页

作者： Muhammad R.Baig Robert D.Beck Jennifer L.Wilson Jennifer A.Lemmer Adeel Meraj Eric C.Meyer Jim Mintz Alan L.Peterson John D.Roache Mental Health South Texas Veterans Healthcare System116 A7400 Merton Minter BIvdSan AntonioTX 78229USA Polytrauma Rehabilitation Center South Texas Veterans Healthcare SystemSan AntonioTXUSA Department of Psychiatry and Behavioral Sciences University of Texas Health Science Center at San AntonioSan AntonioTXUSA Department of veterans Affairs VISN 17 Center of Excellence for Research on Returning War veterans WacoTXUSA central texas veterans healthcare system WacoTXUSA Department of Psychology and Neuroscience Baylor UniversityWacoTXUSA Department of Epidemiology and Biostatistics University of Texas Health Science Center at San AntonioSan AntonioTXUSA Department of Psychology University of Texas at San AntonioSan AntonioUSA Department of Pharmacology University of Texas Health Science Center at San AntonioSan AntonioTXUSA

Background: Selective serotonergic reuptake inhibitors(SSRIs) are first-line pharmacologic treatments for patients with posttraumatic stress disorder(PTSD), but must be given over extended period of time before the onset of action. The use of SSRIs in PTSD patients with mild traumatic brain injury(m TBI) is problematic since SSRIs could exacerbate post-concussion syndrome(PCS) symptoms. VA/DOD guidelines identify trauma-focused psychotherapy as the best evidence-based treatment for PTSD, but overall effectiveness is limited by reduced levels of patient engagement and retention. A previous study from this research group suggested that quetiapine monotherapy, but not risperidone or valproate, could increase engagement in trauma-focused ***: We report the study protocol of a pilot study funded under the South-central Mental Illness Research, Education, and Clinical Center pilot study program from the U.S. Department of veterans Affairs. This randomized, open-label study was designed to evaluate the feasibility of completing a randomized trial of quetiapine vs. treatment as usual to promote patient engagement in PTSD patients with a history of m ***: We expect that the success of this ongoing study should provide us with the preliminary data necessary to design a full-scale randomized trial. Positive efficacy results in a full-scale trial should inform new VA guidelines for clinical practice by showing that quetiapine-related improvements in patient engagement and retention may be the most effective approach to assure that VA resources achieve the best possible outcome for *** registration: NCT04280965.

关键词： Quetiapine Trauma-focused psychotherapy Posttraumatic stress disorder Mild traumatic brain injury veterans

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Increased susceptibility of aging gastric mucosa to injury and delayed healing:Clinical implications

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World Journal of Gastroenterology 2018年第42期24卷 4721-4727页

作者： Andrzej S Tarnawski Amrita Ahluwalia Department of Gastroenterology Research University of California Irvine and the Veterans Administration Long Beach Healthcare System

In this editorial we comment on the article by Fukushi K et al published in the recent issue of the World Journal of Gastroenterology 2018; 24(34): 3908-3918. We focus specifically on the mechanisms of the anti-thrombotic action of aspirin, gastric mucosal injury and aging-related increased susceptibility of gastric mucosa to injury. Aspirin is widely used not only for the management of acute and chronic pain and arthritis, but also importantly for the primary and secondary prevention of cardiovascular events such as myocardial infarcts and strokes. Clinical trials have consistently shown that antiplatelet therapy with long term, low dose aspirin(LDA)-75 to 325 mg daily, dramatically reduces the risk of non-fatal myocardial infarcts, stroke and mortality in patients with established arterial diseases. However, such treatment considerably increases the risk of gastrointestinal(GI) ulcerations and serious bleeding by > 2-4 fold, especially in aging individuals. This risk is further increased in patients using LDA together with other antiplatelet agents, other nonsteroidal anti-inflammatory agents(NSAIDs) and/or alcohol, or in patients with Helicobacter pylori(H. pylori) infection. Previous studies by our group and others have demonstrated prominent structural and functional abnormalities in gastric mucosa of aging individuals(which we refer to as aging gastric mucosa or "aging gastropathy") compared to the gastric mucosa of younger individuals. Aging gastric mucosa has impaired mucosal defense, increased susceptibility to injury by a variety of noxious agents such as aspirin, other NSAIDs and ethanol, and delayed and impaired healing of injury. The mechanism underlying these abnormalities of aging gastric mucosa include reduced mucosal blood flowcausing hypoxia, upregulation of PTEN, activation of proapoptotic caspase-3 and caspase-9, and reduced survivin(anti-apoptosis protein), importin-α(nuclear transport protein), vascular endothelial growth factor, and nerve grow

关键词： Aging gastric mucosa Injury Low dose aspirin Platelets Cyclooxygenase-1 Cyclooxygenase-2 Thromboxane A-2

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Functional significance of erythropoietin receptor on tumor cells

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World Journal of Gastroenterology 2006年第46期12卷 7460-7462页

作者： Kodetthoor B Udupa Reynolds Institute on Aging Department of Geriatrics Physiology and Biophysics University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System 4300 West Seventh Street Little Rock AR United States

Erythropoietin (Epo) is the regulator of red blood cell formation. Its receptor (EpoR) is now found in many cells and tissues of the body. EpoR is also shown to occur in tumor cells and Epo enhances the proliferation of these cells through cell signaling. EpoR antagonist can reduce the growth of the tumor in vivo. In view of our current knowledge of Epo, its recombinant forms and receptor, use of Epo in cancer patients to enhance the recovery of hematocrit after chemotherapy treatment has to be carefully evaluated.

关键词： Erythropoietin Tumor cell Receptor Cell signaling Proliferation Erythroid cell

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Endothelial cells and blood vessels are major targets for COVID-19-induced tissue injury and spreading to various organs

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World Journal of Gastroenterology 2022年第3期28卷 275-289页

作者： Andrzej S Tarnawski Amrita Ahluwalia Gastroenterology Research Department University of California Irvine and the Veterans Administration Long Beach Healthcare SystemLong BeachCA 90822United States Research Service Veterans Administration Long Beach Healthcare SystemLong BeachCA 90822United States

The coronavirus disease 2019(COVID-19)infected so far over 250 million people and caused the death of over 5 million ***,diabetes,and cardiovascular diseases,conditions with preexisting impaired endothelial functions predispose to *** respiratory epithelium is the main route of virus entry,the endothelial cells(ECs)lining pulmonary blood vessels are also an integral part of lung injury in COVID-19 ***-19 not only affects the lungs and respiratory system but also gastrointestinal(GI)tract,liver,pancreas,kidneys,heart,brain,and *** vessels are likely conduits for the virus dissemination to these distant ***,ECs are also critical for vascular regeneration during injury/lesions healing and restoration of vascular *** World Journal of Gastroenterology has published in last two years over 67 outstanding papers on COVID-19 infection with a focus on the GI tract,liver,pancreas,etc.,however,the role of the endothelial and vascular components as major targets for COVID-19-induced tissue injury,spreading to various organs,and injury healing have not been sufficiently *** the present article,we focus on these subjects and on current treatments including the most recent oral drugs molnupiravir and paxlovid that show a dramatic,significant efficacy in controlling severe COVID-19 infection.

关键词： Endothelial cells Impaired endothelial function Blood vessels SARS-CoV-2 COVID-19 Cytokine storm

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Can Weather Influence the Prevalence of Acute-on-chronic Liver Failure?

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Journal of Clinical and Translational Hepatology 2019年第4期7卷 285-286页

作者： Matthew McMillin central texas veterans Health Care system TempleTXUSA Department of Internal Medicine University of Texas at Austin Dell Medical SchoolAustinTXUSA

Acute-on-chronic liver failure(ACLF) results from an acute insult that occurs in patients with chronic liver disease,ultimately leading to liver *** underlying chronic liver dysfunction can be characterized into three categories:chronic liver disease with no cirrhosis;compensated liver cirrhosis;decompensated *** underlying chronic liver diseases are numerous and include alcoholic liver disease,viral hepatitis(types B and C),nonalcoholic fatty liver disease,and other underlying etiologies.1 Acute liver injury can arise from viral hepatitis infections(types A,B,and E),acetaminophen toxicity,drug-induced liver injury,toxin exposure,and numerous other hepatic and extrahepatic causes including heat stroke.2 Due to the numerous aspects of pathology that can generate both the chronic and acute components of ACLF,these patients can have significantly different pathology *** makes ACLF difficult to clas-sify,and this is evident by the different ACLF definitions being used by the Asian Pacific Association for the Study of the Liver,the European Association for the Study of the Liver–Chronic Liver Failure Consortium,and the North American Consortium for the Study of End-Stage Liver Disease with regards to mor-tality,presence of organ failure,inclusion/exclusion criteria,and other disease characteristics.3,4 In addition,these differ-ent definitions of ACLF,depending on which definition is used,could potentially influence the outcomes of studies depending upon the metric investigated.

关键词： Liver Acute acute

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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

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Role of the melatonin/menin signaling in the regulation of cholangiocarcinoma growth

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Cancer Biology & Medicine 2018年第S1期15卷 3-4页

作者： Shannon Glaser Gianfranco Alpini central texas veterans Health Care system Baylor Scott&White and Texas A&M UniversityTempleTexasUSA

Objective:There is decreased expression of arylalkylamine N-acetyltransferase(the rate-limiting enzyme regulating melatonin synthesis)and the clock gene,Per1 and increased expression of the MT1 melatonin receptor subtype in cholangiocarcinoma(CCA).This study tested the hypothesis that the inhibitory effects of the melatonin/MT1/Per1 axis on CCA growth are mediated by inhibition of miR-24.

关键词： Role melatonin regulation

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Carcinoma of the gastroesophageal junction in Chinese patients

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World Journal of Gastroenterology 2012年第48期18卷 7134-7140页

作者： Qin Huang Department of Pathology Nanjing Drum Tower Hospital Department of Pathology and Laboratory Medicine Veterans Affairs Boston Healthcare System and Harvard Medical School

Carcinoma of the gastroesophageal junction(GEJ) is defined as carcinoma that crosses the GEJ line,irrespective of where the tumor epicenter is *** group of cancer is rare but *** on study results from the majority of epidemiologic and clinicopathologic investigations carried out in Western countries,this cancer is believed to arise from Barrett's esophagus(BE) and includes both distal esophageal and proximal gastric carcinomas because of similar characteristics in epidemiology,clinicopathology,and molecular pathobiology in relation to *** such,the most recent American Joint Committee on Cancer staging manual requires staging all GEJ carcinomas with the rule for esophageal adenocarcinoma(EA).This mandate has been challenged recently by the data from several studies carried out mainly in Chinese *** emerging evidence derivedfrom those studies suggests:(1) both BE and EA are uncommon in the Chinese population;(2) almost all GEJ cancers in Chinese arise in the proximal stomach and show the features of proximal gastric cancer,not those of EA;(3) application of the new cancer staging rule to GEJ cancer of Chinese patients cannot stratify patients' prognosis effectively;and(4) prognostic factors of GEJ cancer in Chinese are similar,but not identical,to those of *** conclusion,the recent evidence suggests that GEJ cancer in Chinese shows distinct clinicopathologic characteristics that are different from *** investigations in molecular pathology may help illustrate the underlying pathogenesis mechanisms of this cancer in Chinese patients and better manage patients with this fatal disease.

关键词： Esophagus Stomach Cancer Gastroesophageal junction Staging Barrett's esophagus

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