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Genetic Evidence for XPC-KRAS Interactions During Lung Cancer Development

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Journal of Genetics and Genomics 2015年第10期42卷 589-596页

作者： Xiaoli Zhang Nonggao He Dongsheng Gu Jeff Wickliffe James Salazar Istavan Boldogh Jingwu Xie department of Pediatrics Wells Center for Pediatrics Research Indiana University School of Medicine University of Texas Medical Branch School of Medicine Cancer Center department of Global Environmental Health Sciences Tulane University School of Public Health Biology department Galveston College department of Microbiology and Immunology University of Texas Medical Branch School of Medicine

Lung cancer causes more deaths than breast, colorectal and prostate cancers combined. Despite major advances in targeted therapy in a subset of lung adenocarcinomas, the overall 5-year survival rate for lung cancer worldwide has not significantly changed for the last few decades. DNA repair deficiency is known to contribute to lung cancer development. In fact, human polymorphisms in DNA repair genes such as xeroderma pigmentosum group C （XPC） are highly associated with lung cancer incidence. However, the direct genetic evidence for the role of XPC for lung cancer development is still lacking. Mutations of the Kirsten rat sarcoma viral oncogene homolog （Kras） or its downstream effector genes occur in almost all lung cancer cells, and there are a number of mouse models for lung cancer with these mutations. Using activated Kras, KrasTM, as a driver for lung cancer development in mice, we showed for the first time that mice with KrasTM and Xpc knockout had worst outcomes in lung cancer development, and this phenotype was associated with accumulated DNA damage. Using cultured ceils, we demonstrated that induced expression of oncogenic ***12v led to increased levels of reactive oxygen species （ROS） as well as DNA damage, and both can be suppressed by anti-oxidants. Our results suggest that XPC may help repair DNA damage caused by KRAS-mediated production of ROS.

关键词： Lung cancer XPC Kras ROS

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Successful liver transplantation for acute sickle cell intrahepatic cholestasis: A case report and review of the literature

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World Journal of Hepatology 2020年第3期12卷 108-115页

作者： Motasem Alkhayyat Mohannad Abou Saleh Mohammad Zmaili vedha Sanghi Tavankit Singh Carol Rouphael C Roberto Simons-Linares Carlos Romero-Marrero William D Carey Christina C Lindenmeyer department of internal medicine Cleveland ClinicClevelandOH 44195United States Digestive Disease&Surgery Institute Department of GastroenterologyHepatology&NutritionCleveland ClinicClevelandOH 44195United States

BACKGROUND Sickle cell hepatopathy(SCH)is an inclusive term referring to any liver dysfunction among patients with sickle cell *** sickle cell intrahepatic cholestasis is one of the rarest and most fatal presentations of *** present the 23rd reported case of liver transplantation(LT)for SCH;a rare case of acute sickle cell intrahepatic cholestasis managed with LT from a hepatitis C virus(HCv)nucleic acid amplification test positive *** SUMMARY A 29-year-old male with a past medical history of sickle cell disease presented with vaso-occlusive pain *** examination,he had jaundice and a soft,nontender *** he was alert and fully oriented;within 24 h he developed new-onset *** evaluation was notable for hyperbilirubinemia,leukocytosis,anemia,thrombocytopenia,acute kidney injury and elevated international normalized ratio(INR).Imaging by ultrasound and computed tomography scan suggested a cirrhotic liver morphology with no evidence of biliary ductal *** patient was diagnosed with acute sickle cell intrahepatic cholestasis after excluding competing etiologies of acute liver *** underwent LT from an HCv nucleic acid amplification test positive donor 9 d after initial *** liver explant was notable for widespread sinusoidal dilatation with innumerable clusters of sickled red blood cells and *** postoperative day 3,HCv RNA was detectable in the patient's peripheral blood and anti-HCv therapy with glecaprevir/pibrentasvir was initiated on postoperative day *** subsequently achieved sustained virologic response after completing 3 mo of therapy and has been followed clinically for 12 mo *** This case highlights the utility of LT as a viable treatment option for acute sickle cell intrahepatic cholestasis.

关键词： Case report Sickle cell hepatopathy Acute intrahepatic cholestasis Liver transplant Hepatitis C virus Post-operative surveillance

Actionable Genotypes and Their Association with Life Span in Iceland

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四川生理科学杂志 2024年第4期46卷 208-208页

作者： Brynjar O Jensson From deCODE Genetics-Amgen (B.O.J. G.A.A. H.K. R.F. H. Helgason A.O. G.S. H.P.E. G.H.H. B.A.A. H.J. G.R.O. A. Sturluson S.A.G. G.A.T. F.Z. K.H.S.M. G.P. A. Sigurdsson Adalbjorg Jonasdottir Aslaug Jonasdottir M.K.M. A. Helgadottir V.S. J.G. S.N.S. D.O.A. J.S. O.T.M. G.M. B.V.H. A. Helgason H.S. I.J. H. Holm T.R. U.T. D.F.G. K.S. P.S.) the Faculty of Medicine School of Health Sciences (G.A.A. M.K.M. R.H. D.O.A. I.J. U.T. K.S.) the Department of Anthropology (K.H.S.M. A. Helgason) and the School of Engineering and Natural Sciences (H. Helgason G.H.H. D.F.G.) University of Iceland the Departments of Urology (R.H.) Clinical Biochemistry (I.O.) Oncology (O.T.J.) Medicine (D.O.A.) and Immunology (I.J.) Landspitali-the National University Hospital of Iceland and the School of Science and Engineering Reykjavik University (B.V.H.) - all in Reykjavik Iceland.

Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are *** of the... 详细信息

关键词： College action Ice

Genomic analysis of indigenous goats in Southwest Asia reveals evidence of ancient adaptive introgression related to desert climate

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Zoological Research 2023年第1期44卷 20-29页

作者： Hojjat Asadollahpour Nanaei Yudong Cai Akil Alshawi Jiayue Wen Tanveer Hussain Wei-Wei Fu Nai-Yi Xu Abdulameer Essa Johannes ALenstra Xihong Wang Yu Jiang Key Laboratory of Animal Genetics Breeding and Reproduction of Shaanxi ProvinceCollege of Animal Science and TechnologyNorthwest A&F UniversityYanglingShaanxi 712100China department of internal and Preventive medicine College of Veterinary MedicineUniversity of BaghdadIraqi Ministry of Higher Education and Scientific ResearchBagdad 10090Iraq department of Molecular Biology Virtual University of PakistanLahore 54000Pakistan Animal Genetics Resources department Directorate of Animal Resourcesthe Ministry of Iraqi AgricultureBaghdad 10081Iraq Faculty of veterinary medicine Utrecht University3508 TD UtrechtThe Netherlands

Understanding how evolutionary pressures related to climate change have shaped the current genetic background of domestic animals is a fundamental pursuit of biology. Here, we generated wholegenome sequencing data from native goat populations in Iraq and Pakistan. Combined with previously published data on modern, ancient(Late Neolithic to Medieval periods), and wild Capra species worldwide, we explored the genetic population structure, ancestry components, and signatures of natural positive selection in native goat populations in Southwest Asia(SWA). Results revealed that the genetic structure of SWA goats was deeply influenced by gene flow from the eastern Mediterranean during the Chalcolithic period, which may reflect adaptation to gradual warming and aridity in the region. Furthermore, comparative genomic analysis revealed adaptive introgression of the KITLG locus from the Nubian ibex(C. nubiana) into African and SWA goats. The frequency of the selected allele at this locus was significantly higher among goat populations located near northeastern Africa. These results provide new insights into the genetic composition and history of goat populations in the SWA region.

关键词： Goat Adaptation KITLG Southwest Asia Nubian ibex

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Impact of endoscopy-based research on quality of life in healthy volunteers

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World Journal of Gastroenterology 2010年第4期16卷 467-473页

作者： Alexander Link Gerhard Treiber Brigitte Peters Thomas Wex Peter Malfertheiner department of Gastroenterology Hepatology and Infectious Diseases Otto-von-Guericke University Leipziger St.44 39120 Magdeburg Germany department of internal medicine Division of Gastroenterology Baylor Research Institute Baylor UniversityMedical Center 3500 Gaston Ave (H-250) Dallas TX 75246United States department of Gastroenterology Oncology and General Internal Medicine Zollernalb Clinic Tuebinger St.30 72336 Balingen Germany Institute for Biometry and Medical Informatics Otto-von-Guericke University Leipziger St. 44 39120 Magde-burg Germany department of Gastroenterology Hepatology and Infectious Diseases Otto-von-Guericke University Leipziger St.44 39120 MagdeburgGermany

AIM:To study the impact of an endoscopy-based long-term study on the quality of life in healthy volunteers(Hv).METHODS:Ten Hv were included into a long-term prospective endoscopy-based placebo-controlled trial with 15 endoscopic examinations per person in 5 different drug *** completed short form-36(SF-36) and visual analog scale-based questionnaires(vAS) for different abdominal symptoms at days 0,7 and 14 of each drug *** wereperformed according to short-and long-term changes and compared to the control ***:All Hv completed the study with duration of more than 6 *** quality of life score was comparable to a general *** of the SF-36 questionnaires showed no significant changes in physical,mental and total scores,either in a short-term perspective due to different medications,or to potentially endoscopic procedure-associated long-term cumulative *** to SF-36,vAS revealed no significant changes in total scores for pathological abdominal symptoms and remained unchanged over the time course and when compared to the control ***:This study demonstrates that quality of life in Hv is not significantly affected by a longterm endoscopy-based study with multiple endoscopic procedures.

关键词： Endoscopy research Ethics Healthy volunteers Quality of life

Antisense oligonucleotides-induced local blockade of T-bet expression leads to airway inflammation in rats

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Acta Pharmacologica Sinica 2006年第5期27卷 561-567页

作者： Gang WANG~2 Chun-tao LIU~(3,4) Zeng-li WANG~3 Li-li JIANG~5 Cun-liang YAN~6 Feng-min LUO~3 ~2department of Integrated Traditional Chinese and Western medicine.West China Hospital.Sichuan University,Chengdu 610041,China.~3department of Respiratory medicine,West China Hospital,Sichuan University.Chengdu 610041.China ~5department of Pathology,West China Hospital.Sichuan University,Chengdu 610041,China:~6department of Laboratory medicine.Shenzhen Hospital,Peking University.Shenzhen 518036,China department of Integrated Traditional Chinese and Western medicine West China Hospital Sichuan University Chengdu China department of Respiratory medicine West China Hospital Sichuan University Chengdu China department of Pathology West China Hospital Sichuan University Chengdu China department of Laboratory medicine Shenzhen Hospital Peking University Shenzhen China

Aim:To explore whether local blockade of T-box expressed in T cells (T-bet)expression in the lungs could lead to airway ***:Twenty-fourrats were randomly divided into 4 groups:saline group,ovalbumin (OvA)-sensi-tized group,nonsense group,and the antisense *** OvA-sensitized ratswere sensitized and challenged with OvA,and the rats in the nonsense andantisense groups were subjected to an aerosol delivery of the nonsense andantisense oligonucleotides (AS-ODN) of T-bet (0.1%,w/v).The levels of inter-feron-γ(IFN-γ),interleukin-4(IL-4),and IL-5 in the bronchoalveolar lavage fluid(BALF) were detected by ELISA,and the mRNA and the protein expression ofT-bet and GATA-3 genes were examined by in situ hybridization and Western blotanalysis,***:The expression of T-bet mRNA and protein in thelungs of the rats in the antisense group were inhibited *** lungs ofthe rats in the antisense and OvA-sensitized groups showed eosinophil and lym-phocyte inflammatory infiltration,and eosinophilia located predominantly aroundthe *** number of GATA-3 mRNA-positive cells and the level of GATA-3protein in the lungs of the rats in the antisense and the OvA-sensitized groupssignificantly *** level of IL-4 and IL-5 in the BALF in the antisenseand OvA-sensitized groups were elevated,but the level of IFN-γ ***:Antisense ODN-induced local blockade of T-bet expres-sion leads to airway inflammation with a selective alteration in patterns of cytokineexpression and recruitment of eosinophil cells similar to that in the OvA-sensitizedanimals.

关键词： airway inflammation antisense oligonucleotides GATA3 transcription factor interferon type Ⅱ interleukin-4 interleukin-5 Tbox expressed in T cells

Electrical stimulation promotes regeneration of injured oculomotor nerves in dogs

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Neural Regeneration Research 2016年第10期11卷 1666-1669页

作者： Lei Du Min Yang Liang Wan Xu-hui Wang Shi-ting Li department of Gerontology Xinhua Hospital Shanghai Jiao Tong University School of Medicine department of Neurosurgery Xinhua Hospital Shanghai Jiao Tong University School of Medicine

Functional recovery after oculomotor nerve injury is very poor. Electrical stimulation has been shown to promote regeneration of injured nerves. We hypothesized that electrical stimulation would improve the functional recovery of injured oculomotor nerves. Oculomotor nerve injury models were created by crushing the right oculomotor nerves of adult dogs. Stimulating electrodes were positioned in both proximal and distal locations of the lesion, and non-continuous rectangular, biphasic current pulses （0.7 v, 5 Hz） were administered 1 hour daily for 2 consecutive weeks. Analysis of the results showed that electrophysiological and morphological recovery of the injured oc- ulomotor nerve was enhanced, indicating that electrical stimulation improved neural regeneration. Thus, this therapy has the potential to promote the recovery of oculomotor nerve dysfunction.

关键词： nerve regeneration oculomotor nerve electrical stimulation dog nerve injury model cranial nerve peripheral nerve

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Assessment of Arterial Stiffening and vascular Calcifications in End‐Stage Renal Disease Patients

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World Journal of Cardiovascular Diseases 2017年第4期7卷 131-143页

作者： Mahmoud Kamal Elsamman Mohamed Abdel Wahab Ezzat Medhat Ibraheem Mohammad Raghda Gamal Mostafa Ali Taha Ali Hassan internal medicine department Sohag Faculty of Medicine Sohag University Sohag Egypt Diagnostic Radiology department Sohag Faculty of Medicine Sohag University Sohag Egypt

Background and Objective: Epidemiological and clinical studies have shown that vascular calcification and arterial vascular stiffness are associated with all-cause and cardiovascular (Cv) mortality in the general populations and end-stage renal disease (ESRD) patients. The objective of this study was the assessment of arterial stiffness and vascular calcification in ESRD patients in Sohag University Hospital. Patients and Methods: In this cross-sectional descriptive study, 100 patients with ESRD (63 males and 37 females) were included. The patients were on regular hemodialysis (HD) for 65.18 ± 50.25 months. Arterial stiffness was measured by brachial pulse pressure (PP). A simple vascular calcification score (SvCS) based on plain radiographic films of pelvis and hands was used for assessment of vascular calcification. The patients undergoing clinical evaluation and serum calcium, phosphorus and parathyroid hormone (PTH) were obtained. Results: PP > 70 mmHg was observed in 24 patients (24%) and vascular calcifications were detected in 50 patients (50%). SvCS ≥ 3 was observed in 36 patients (36%) and 10 patients (10%) had both SvCS ≥ 3 and PP > 70 mmHg. PP > 70 was significantly associated with presence of vascular disease (odds ratio;5, 95% CI = 1.56 - 16.01;P = 0.007). In multivariate analysis, PP > 70 was independently associated with elevated systolic blood pressure (odds ratio;1.34, 95% CI = 1.11 - 1.6;P = 0.002) and serum PTH (odds ratio;1.004, 95% CI = 1 - 1.008;P = 0.03). SvCS ≥ 3 was association with age (odds ratio;1.05, 95% CI = 1.02 - 1.09;P = 0.003) and presence of vascular disease (odds ratio;3.19, 95% CI = 1.3 - 7.85;P = 0.01). Elevated systolic blood pressure was independently associated with SvCS ≥ 3 (odds ratio;1.08, 95% CI = 1.03 - 1.14;P = 0.002). Conclusion: Arterial stiffness and vascular calcifications are common in patients with ESRD on regular hemodialysis. PP and SvCS are simple and inexpensive methods in assessment of vascular calcifications

关键词： Arterial Stiffness vascular Calcification Pulse Pressure Haemodialysis

Evaluation of oxidative stress levels in obesity and diabetes by the free oxygen radical test and free oxygen radical defence assays and correlations with anthropometric and laboratory parameters

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World Journal of Diabetes 2020年第5期11卷 193-201页

作者： Mihnea-Alexandru Găman Mirela Elena Epîngeac Camelia Cristina Diaconu Amelia Maria Găman "Carol Davila"University of medicine and Pharmacy Bucharest 050474Romania department of Hematology Center of Hematology and Bone Marrow TransplantationFundeni Clinical InstituteBucharest 022328Romania department of Pathophysiology University of Medicine and Pharmacy of CraiovaCraiova 200349Romania internal medicine Clinic Clinical Emergency Hospital of BucharestBucharest 014461Romania Clinic of Hematology Filantropia City HospitalCraiova 200143Romania

BACKGROUND Obesity and diabetes are associated with high levels of oxidative *** Romanian patients with obesity and(or)diabetes,this association has not been sufficiently *** To evaluate oxidative stress in obese and(or)diabetic subjects and to investigate the possible correlations between oxidative stress and anthropometric/biochemical *** Oxidative stress was evaluated from a single drop of capillary *** oxygen species(ROS)were evaluated using the free oxygen radical test(FORT).The free oxygen radical defence(FORD)assay was used to measure antioxidant *** FORT levels were higher in obese subjects(3.04±0.36 mmol/L H2O2)vs controls(2.03±0.14 mmol/L H2O2)(Pvels were lower in obese subjects(1.27±0.13 mmol/L Trolox)vs controls(1.87±1.20 mmol/L Trolox)(P=0.0072).Obese diabetic subjects had higher FORT values(3.16±0.39 mmol/L H2O2)vs non-diabetic counterparts(2.99±0.33 mmol/L H2O2)(P=0.0233).In obese subjects,FORT values correlated positively with body mass index(BMI)(r=0.48,P=0.0000),waist circumference(WC)(r=0.31,P=0.0018),fasting plasma glucose(FPG)(r=0.31,P=0.0017),total cholesterol(TC)(r=0.27,P=0.0068)and uric acid(r=0.36,P=0.0001).FORD values correlated negatively with BMI(r=-0.43,P=0.00001),WC(r=-0.28,P=0.0049),FPG(r=-0.25,P=0.0130),TC(r=-0.23,P=0.0198)and uric acid(r=-0.35,P=0.0002).In obese diabetic subjects,FORT values correlated positively with BMI(r=0.49,P=0.0034)and TC(r=0.54,P=0.0217).FORD values were negatively associated with BMI(r=-0.54,P=0.0217)and TC(r=-0.58,P=0.0121).CONCLUSION Oxidative stress levels,as measured by the FORT and FORD assays,were higher in obese subjects vs *** levels were elevated in diabetic obese patients vs obese non-diabetic patients and controls.

关键词： Oxidative stress Obesity Diabetes Reactive oxygen species Antioxidants Dyslipidaemia