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| 1 | Recent advances in gastric cancer early diagnosis显示文摘Gastric cancer(GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva,stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC. | Laura Necula Lilia Matei Denisa Dragu Ana I Neagu Cristina Mambet Saviana Nedeianu Coralia Bleotu Carmen C Diaconu Mihaela Chivu-Economescu | 2019 | World Journal of Gastroenterology2019，25，17： | 70 |
| 2 | Daily genetic profiling indicates JAK/STAT signaling promotes early hepatic stellate cell transdifferentiation显示文摘AIM: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation. METHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor. RESULTS: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SMA, PDGFR and TGFβR. CONCLUSION: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation. | Ashley M Lakner Cathy C Moore Alyssa A Gulledge Laura W Schrum | 2010 | World Journal of Gastroenterology2010，16，40： | 23 |
| 3 | New therapeutic options opened by the molecular classification of gastric cancer显示文摘Gastric cancer(GC) is one of the most lethal and aggressive cancers, being the third cause of cancer related death worldwide. Even with radical gastrectomy and the latest generation of molecular chemotherapeutics, the numbers of recurrence and mortality remains high. This is due to its biological heterogeneity based on the interaction between multiple factors, from genomic to environmental factors, diet or infections with various pathogens. Therefore, understanding the molecular characteristics at a genomic level is critical to develop new treatment strategies. Recent advances in GC molecular classification provide the unique opportunity to improve GC therapy by exploiting the biomarkers and developing novel targeted therapy specific to each subtype. This article highlights the molecular characteristics of each subtype of gastric cancer that could be considered in shaping a therapeutic decision, and also presents the completed and ongoing clinical trials addressed to those targets. The implementation of the novel molecular classification system will allow a preliminary patient selection for clinical trials, a mandatory issue if it is desired to test the efficacy of a certain inhibitor to the given target. This will represent a substantial advance as well as a powerful tool for targeted therapy. Nevertheless, translating the scientific results into new personalized treatment opportunities is needed in order to improve clinical care, the survival and quality of life of patients with GC. | Mihaela Chivu-Economescu Lilia Matei Laura G Necula Denisa L Dragu Coralia Bleotu Carmen C Diaconu | 2018 | World Journal of Gastroenterology2018，24，18： | 14 |
| 4 | Diffusion-weighted magnetic resonance imaging to predict response of hepatocellular carcinoma to chemoembolization显示文摘AIM: To investigate whether intra-procedural diffusion- weighted magnetic resonance imaging can predict response of hepatocellular carcinoma (HCC) during trans- catheter arterial chemoembolization (TACE). METHODS: Sixteen patients (15 male), aged 59 ±11 years (range: 42-81 years) underwent a total of 21 separate treatments for unresectable HCC in a hybrid magnetic resonance/interventional radiology suite. Ana- tomical imaging and diffusion-weighted imaging (b = 0, 500 s/mm2) were performed on a 1.5-T unit. Tumor enhancement and apparent diffusion coefficient (ADC, mm2/s) values were assessed immediately before and at 1 and 3 mo after TACE. We calculated the percent change (PC) in ADC values at all time points. We compared follow-up ADC values to baseline values using a paired t test (α = 0.05). RESULTS: The intra-procedural sensitivity, specificity, and positive and negative predictive values (%) for detecting a complete or partial 1-mo tumor response using ADC PC thresholds of ±5%, ±10%, and ±15% were 77, 67, 91, and 40; 54, 67, 88, and 25; and 46, 100, 100, and 30, respectively. There was no clear predictive value for the 3-mo follow-up. Compared to baseline, the immediate post-procedure and 1-mo mean ADC values both increased; the latter obtaining statistical significance (1.48 ± 0.29 mm2/s vs 1.65 ± 0.35 × 10-3 mm2/s, P < 0.014). CONCLUSION: Intra-procedural ADC changes of > 15% predicted 1-mo anatomical HCC response with the greatest accuracy, and can provide valuable feedback at the time of TACE. | Johnathan C Chung Neel K Naik Robert J Lewandowski Mary F Mulcahy Laura M Kulik Kent T Sato Robert K Ryu Riad Salem Andrew C Larson Reed A Omary | 2010 | World Journal of Gastroenterology2010，16，25： | 13 |
| 5 | Therapies targeting cancer stem cells: Current trends and future challenges显示文摘Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers. | Denisa L Dragu Laura G Necula Coralia Bleotu Carmen C Diaconu Mihaela Chivu-Economescu | 2015 | World Journal of Stem Cells2015，7，9： | 10 |
| 6 | Nonalcoholic fatty liver disease in patients with inflammatory bowel disease: Beyond the natural history显示文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a frequently reported condition in patients with inflammatory bowel disease(IBD).Both intestinal inflammation and metabolic factors are believed to contribute to the pathogenesis of IBDassociated NAFLD.AIM To evaluate the prevalence of steatosis and liver fibrosis(LF)in a cohort of IBD patients and the identification of metabolic-and IBD-related risk factors for NAFLD and LF.METHODS IBD patients were consecutively enrolled from December 2016 to January 2018.Demographic,anthropometric and biochemical data were collected so as eating habits.Abdominal ultrasound and transient elastography were performed to evaluate the presence of NAFLD and LF respectively.RESULTS A total of 178 consecutive patients were enrolled and included in the analysis(95 Ulcerative colitis,83 Crohn’s disease).NAFLD was detected by imaging in 72(40.4%)patients.Comparison between patients with and without NAFLD showed no significant differences in terms of IBD severity,disease duration,location/extension,use of IBD-related medications(i.e.,steroids,anti-TNFs,and immunomodulators)and surgery.NAFLD was significantly associated with the presence of metabolic syndrome[MetS;odds ratio(OR):4.13,P=0.001]and obesity defined by body mass index(OR:9.21,P=0.0002).IBD patients with NAFLD showed higher caloric intake and lipid consumption than those without NAFLD,regardless disease activity.At the multivariate analysis,male sex,advanced age and high lipid consumption were independent risk factors for the development of NAFLD.An increased liver stiffness was detected in 21 patients(16%)and the presence of MetS was the only relevant factor associated to LF(OR:3.40,P=0.01).CONCLUSION In this study,we demonstrate that risk factors for NAFLD and LF in the IBD population do not differ from those in the general population. | Salvatore Magrì Danilo Paduano Fabio Chicco Arianna Cingolani Cristiana Farris Giovanna Delogu Francesca Tumbarello Mariantonia Lai Alessandro Melis Laura Casula Massimo C Fantini Paolo Usai | 2019 | World Journal of Gastroenterology2019，25，37： | 8 |
| 7 | Successful endoscopic treatment of an intraductal papillary neoplasm of the bile duct显示文摘We present a case of a 76-year-old man with right upper quadrant abdominal pain and weight loss,who was found to have an intraductal papillary neoplasm of the bile duct(IPNB)of the pancreaticobiliary subtype,deemed curatively resectable.The patient declined surgery and opted for endoscopic therapy.He underwent two sessions of endoscopic retrograde cholangiopancreatography(ERCP)-guided radiofrequency ablation(RFA).Ten months later,no evidence of recurrence was identified on repeat ERCP.To our knowledge,this is the first reported case of successful use of RFA as a primary treatment modality for resectable IPNB. | Nikola S Natov Laura C Horton Sanjay R Hegde | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，5： | 5 |
| 8 | Magnetic resonance imaging may predict deep remission in patients with perianal fistulizing Crohn's disease显示文摘AIM To evaluate the imaging course of Crohn's disease(CD) patients with perianal fistulas on long-term maintenance anti-tumor necrosis factor(TNF)-α therapy and identify predictors of deep remission.METHODS All patients with perianal CD treated with anti-TNF-α therapy at our tertiary care center were evaluated by magnetic resonance imaging(MRI) and clinical assessment. Two MR examinations were performed: at initiation of anti-TNF-α treatment and then at least 2 years after. Clinical assessment(remission, response and non-response) was based on Present's criteria. Rectoscopic patterns, MRI Van Assche score, and MRI fistula activity signs(T2 signal and contrast enhancement) were collected for the two MR examinations. Fistula healing was defined as the absence of T2 hyperintensity and contrast enhancement on MRI. Deep remission was defined as the association of both clinical remission, absence of anal canal ulcers and healing on MRI. Characteristics and imaging patterns of patients with and without deep remission were compared by univariate and multivariate analyses.RESULTS Forty-nine consecutive patients(31 females and 18 males) were included. They ranged in age from 14-70 years(mean, 33 years). MRI and clinical assessment were performed after a mean period of exposure to anti-TNF-α therapy of 40 ± 3.7 mo. Clinical remission, response and non-response were observed in 53.1%, 20.4%, and 26.5% of patients, respectively. Deep remission was observed in 32.7% of patients. Among the 26 patients in clinical remission, 10 had persisting inflammation of fistulas on MRI(T2 hyperintensity, n = 7; contrast enhancement, n = 10). Univariate analysis showed that deep remission was associated with the absence of rectal involvement and the absence of switch of anti-TNF-α treatment or surgery requirement. Multivariate analysis demonstrated that only the absence of rectal involvement(OR = 4.6; 95%CI: 1.03-20.5) was associated with deep remission.CONCLUSION Deep remission is achieved in approximately one third of patients on maintenance anti-TNF-α therapy. Absence of rectal involvement is predictive of deep remission. | Lucie Thomassin Laura Armengol-Debeir Cloé Charpentier Valerie Bridoux Edith Koning Guillaume Savoye Céline Savoye-Collet | 2017 | World Journal of Gastroenterology2017，23，23： | 5 |
| 9 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 10 | CABYR binds to AKAP3 and Ropporin in the human sperm fibrous sheath显示文摘钙绑定酷氨酸调整 phosphorylation 的蛋白质(CABYR ) 是高度多态的钙绑定 tyrosine-/threonine-phosphorylated 和 serine-/threonine-phosphorylated 涉及 capacitation 的含纤维的鞘(FS ) 蛋白质。一个通常认为的领域(氨基酸 12 鈥 ? 8 ) 对类型 II 营地依赖者蛋白质 kinase A (RII ) dimerisation 和抛锚 kinase 蛋白质(AKAP ) 的规章的子单元相应在 N 终点的蛋白质 kinase A 的有约束力的领域建议那 CABYR 可以自我装配并且绑在 AKAP。而且,有证据, CABYR 与 AKAP 限制了相互作用。然而,推进在 CABYR 之间的证据和新关系,包括 AKAP,另外的 FS 蛋白质将在理解 FS 的基本生理学是有用的。在这研究,为不可溶解的蛋白质的 co-immunoprecipitation 的新策略,以及在有集体 spectrometry 和西方的污点的联合的标准 co-immunoprecipitation 方法,被采用探索在 CABYR, AKAP3 和 Ropporin 之间的关系。结果证明 AKAP3 是有由 anti-CABYR-A polyclonal 抗体的 CABYR 的 co-immunoprecipitated,并且,相反地, CABYR 也是有由 anti-AKAP3 polyclonal 抗体的 AKAP3 的 co-immunoprecipitated。包含蛋白质的另一象 RII 一样域, Ropporin,也是有 CABYR 的 co-immunoprecipitated,显示 Ropporin 是 CABYR 的绑定之一合伙。在 CABYR, AKAP3 和 Ropporin 之间的相互作用被酵母证实二混血儿的试金。进一步的分析显示出那 CABYR 不仅由它的 RII 领域绑在 AKAP3 而且除象 RII 一样领域以外通过另外的区域绑在 Ropporin。这是 CABYR 变体形成的第一示范不仅有 scaffolding 蛋白质 AKAP3 而且与在人的精子 FS 的另一象 RII 一样包含域的蛋白质的建筑群。 | Yan-Feng Li Wei He Arabinda Mandal Young-Hwan Kim Laura Digilio Ken Klotz Charles J Flickinger John C Herr | 2011 | Asian Journal of Andrology2011，13，2： | 5 |
| 11 | Approach to medical therapy in perianal Crohn’s disease显示文摘Perianal Crohn’s disease remains a challenging condition to treat and can have a substantial negative impact on quality of life.It often requires combined surgical and medical interventions.Anti-tumor necrosis factor(anti-TNF)therapy,including infliximab and adalimumab,remain preferred medical therapies for perianal Crohn’s disease.Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials.Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn’s disease.Specific issues include evaluation for the presence of perianal sepsis,the treatment target of therapy,the ideal time to commence treatment,whether additional medical therapy should be used in conjunction with anti-TNF therapy,and the duration of treatment.This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn’s disease.It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn’s disease.Lastly,new therapies such as local injection of mesenchymal stem cell therapy will be discussed. | Abhinav Vasudevan David H Bruining Edward V Loftus Jr William Faubion Eric C Ehman Laura Raffals | 2021 | World Journal of Gastroenterology2021，27，25： | 4 |
| 12 | Zn-Mg and Zn-Cu alloys for stenting applications:From nanoscale mechanical characterization to in vitro degradation and biocompatibility显示文摘In the recent decades,zinc(Zn)and its alloys have been drawing attention as promising candidates for bioresorbable cardiovascular stents due to its degradation rate more suitable than magnesium(Mg)and iron(Fe)alloys.However,its mechanical properties need to be improved in order to meet the criteria for vascular stents.This work investigates the mechanical properties,biodegradability and biocompatibility of Zn-Mg and Zn-Cu alloys in order to determine a proper alloy composition for optimal stent performance.Nanoindentation measurements are performed to characterize the mechanical properties at the nanoscale as a function of the Zn microstructure variations induced by alloying.The biodegradation mechanisms are discussed and correlated to microstructure,mechanical performance and bacterial/cell response.Addition of Mg or Cu alloying elements refined the microstructure of Zn and enhanced yield strength(YS)and ultimate tensile strength(UTS)proportional to the volume fraction of secondary phases.Zn-1Mg showed the higher YS and UTS and better performance in terms of degradation stability in Hanks’solution.Zn-Cu alloys presented an antibacterial effect for S.aureus controlled by diffusion mechanisms and by contact.Biocompatibility was dependent on the degradation rate and the nature of the corrosion products. | Claudia García-Mintegui Laura Catalina Córdoba Judit Buxadera-Palomero Andrea Marquina Emilio Jiménez-Piqué Maria-Pau Ginebra JoséLuis Cortina Marta Pegueroles | 2021 | Bioactive Materials2021，6，12： | 4 |
| 13 | Inhibition of the G9a/GLP histone methyltransferase complex modulates anxiety-related behavior in mice显示文摘Epigenetic 基因规定畸形包括精神分裂症和消沉在各种各样的 neuropsychiatric 混乱,以及在心情和焦虑的规定被含有。另外, epigenetic 机制涉及精神病学的药的行动。当前的 anxiolytic 药有新药的重要缺点,和开发被保证。二蛋白质, G9a (也作为 EHMT2 或 KMT1C 知道) 并且 GLP (象 G9a 一样蛋白质,也作为 EHMT1 或 KMT1D 知道) ,它甲醇化物离氨酸 9 histone H3 (H3K9 ) ,能正在答应 anxiolytic 目标。G9a 的出生后的基因大美人减少焦虑相关的行为,与由过去常对待焦虑(amitriptyline, imipramine 和 paroxetine ) 的一些药的 G9a 层次的减小一致。相反地,在有 GLP haplodeficiency 的老鼠有增加的像焦虑的行为。我们寻求了决定是否 G9a/GLP, UNC0642 和 A-366 的二个药理学禁止者,将有类似的效果到基因 G9a/GLP 不足。当予成年老鼠以时,我们发现有任何一个化合物的 G9a/GLP 抑制减少了像焦虑的行为,与在大脑的减少的 H3K9 methylation 一起。相反,到这些的暴露从胚胎的白天加重(E9.5 ) 9.5 增加了像焦虑的行为直到出生并且减少在成人生活的社会相互作用,当 H3K9 methylation 在在成年老鼠的大脑的正常层次时。这些调查结果增强 G9a/GLP 在大脑开发的不同阶段在像焦虑的行为上有不同效果的基因证据,并且建议指向这条 histone methyltransferase 小径能为开发新 anxiolytic 药是有用的。这些数据也建议在 utero 的抗抑郁剂暴露能在成人生活有否定效果,并且这些效果的进一步的调查被保证。 | Dong-yao WANG Joel KOSOWAN James SAMSOM Laura LEUNG Kai-lai ZHANG Ying-xiang LI Yan XIONG Jian JIN Arturas PETRONIS Gabriel OH Albert H C WONG | 2018 | Acta Pharmacologica Sinica2018，39，5： | 4 |
| 14 | Nutritional and health benefits of semi-elemental diets: A comprehensive summary of the literature显示文摘AIM:To critically review and summarize the literature on nutritional and health outcomes of semi-elemental formulations on various nutritionally vulnerable patient populations who are unable to achieve adequate nutrition from standard oral diets.METHODS:We conducted a comprehensive literature search of Pubmed and Embase databases.We manually screened articles that examined nutritional and health outcomes(e.g.,growth,disease activity,gastrointestinal impairment,mortality,and economic impact)among various patient groups receiving semi-elemental diets.This review focused on full-text articles of randomized controlled clinical trials and other intervention studies,but pertinent abstracts and case studies were also included.Results pertaining primarily to tolerance,digestion,and absorption were summarized for each patient population in this systematic review.RESULTS:Results pertaining primarily to tolerance,digestion,and absorption were summarized for each patient population.The efficacy of semi-elemental whey hydrolyzed protein(WHP)diet have been reported in various nutritionally high risk patient populations including-Crohn’s disease,short bowel syndrome,acute and chronic pancreatitis,cerebral palsy,cystic fibrosis,cerebrovascular accidents,human immunodeficiency virus,critically ill,and geriatrics.Collectively,the evidence from the medical literature indicates that feeding with a semi-elemental diet performs as well or better than parenteral or amino acid based diets in terms of toler-ance,digestion,and nutrient assimilation measures across various disease conditions.CONCLUSION:Based on this comprehensive review of the literature,patient populations who have difficulty digesting or absorbing standard diets may be able to achieve improved health and nutritional outcomes through the use of semi-elemental WHP diets. | Dominik D Alexander Lauren C Bylsma Laura Elkayam Douglas L Nguyen | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，2： | 3 |
| 15 | Skeletal muscle mitochondrial health and spinal cord injury显示文摘Mitochondria are the main source of cellular energy production and are dynamic organelles that undergo biogenesis, remodeling, and degradation. Mitochondrial dysfunction is observed in a number of disease states including acute and chronic central or peripheral nervous system injury by traumatic brain injury, spinal cord injury(SCI), and neurodegenerative disease as well as in metabolic disturbances such as insulin resistance, type Ⅱ diabetes and obesity. Mitochondrial dysfunction is most commonly observed in high energy requiring tissues like the brain and skeletal muscle. In persons with chronic SCI, changes to skeletal muscle may include remarkable atrophy and conversion of muscle fiber type from oxidative to fast glycolytic, combined with increased infiltration of intramuscular adipose tissue. These changes contribute to a proinflammatory environment, glucose intolerance and insulin resistance. The loss of metabolically active muscle combined with inactivity predisposes individuals with SCI to type Ⅱ diabetes and obesity. The contribution of skeletal muscle mitochondrial density and electron transport chain activity to the development of the aforementioned comorbidities following SCI is unclear. A better understanding of the mechanisms involved in skeletal muscle mitochondrial dynamics is imperative to designing and testing effective treatments for this growing population. The current editorial will review ways to study mitochondrial function and the importance of improving skeletal muscle mitochondrial health in clinical populations with a special focus on chronic SCI. | Laura C O'Brien Ashraf S Gorgey | 2016 | World Journal of Orthopedics2016，7，10： | 3 |
| 16 | Comparative transcriptomics of Central Asian Vitis vinifera accessions reveals distinct defense strategies against powdery mildew显示文摘Grape powdery mildew(PM),caused by the biotrophic ascomycete Erysiphe necator,is a devastating fungal disease that affects most Vitis vinifera cultivars.We have previously identified a panel of V.vinifera accessions from Central Asia with partial resistance to PM that possess a Ren1-like local haplotype.In this study,we show that in addition to the typical Ren1-associated late post-penetration resistance,these accessions display a range of different levels of disease development suggesting that alternative alleles or additional genes contribute to determining the outcome of the interaction with the pathogen.To identify potential Ren1-dependent transcriptional responses and functions associated with the different levels of resistance,we sequenced and analyzed the transcriptomes of these Central Asian accessions at two time points of PM infection.Transcriptomes were compared to identify constitutive differences and PM-inducible responses that may underlie their disease resistant phenotype.Responses to E.necator in all resistant accessions were characterized by an early up-regulation of 13 genes,most encoding putative defense functions,and a late down-regulation of 32 genes,enriched in transcriptional regulators and protein kinases.Potential Ren1-dependent responses included a hotspot of co-regulated genes on chromosome 18.We also identified 81 genes whose expression levels and dynamics correlated with the phenotypic differences between the most resistant accessions‘Karadzhandahal’,DVIT3351.27,and O34-16 and the other genotypes.This study provides a first exploration of the functions associated with varying levels of partial resistance to PM in V.vinifera accessions that can be exploited as sources of genetic resistance in grape breeding programs. | Katherine C H Amrine Barbara Blanco-Ulate Summaira Riaz Dániel Pap Laura Jones Rosa Figueroa-Balderas M Andrew Walker Dario Cantu | 2015 | Horticulture Research2015，2，1： | 3 |
| 17 | Retinoic acid receptors and cancer: from molecular mechanisms to therapy显示文摘 | Alessandra di Masi Loris Leboffe Elisabetta De Marinis Francesca Pagano Laura Cicconi Cécile Rochette-Egly Francesco Lo Coco Paolo Ascenzi Clara Nervi | 2014 | Molecular Aspects of Medicine2014，，： | 2 |
| 18 | Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression显示文摘 | Brian J Reid Laura J Prevo Patricia C Galipeau Carissa A Sanchez Gary Longton Douglas S Levine Patricia L Blount Peter S Rabinovitch | 2001 | The American Journal of Gastroenterology2001，，10： | 2 |
| 19 | A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification显示文摘MLL-AF4 熔化基因是在在婴儿的高风险的尖锐成淋巴细胞的白血病的一个特点 genomic 错误。尽管 MLL-AF4 在人的开发期间出生前地产生,这很好被建立,它在在 utero 的造血的开发的效果仍然保持未经勘探。我们创造了一个人特定的细胞的系统在 MLL-AF4-expressing 人的胚胎的干细胞(hESCs ) 学习早 hemato-endothelial 开发。介绍的功能的研究,同种细胞的分析和基因表示表明在 hESCs 的 MLL-AF4 的那表情有 phenotypic,功能并且基因表示影响。MLL-AF4 在 hESCs 充当全球 transcriptional 使活跃之物和 homeobox 基因表示的一个积极管理者。机能上地, MLL-AF4 从 hESCs 提高 hemogenic 先锋的说明,但是强烈损害进一步造血的承诺赞成 endothelial 房间命运。MLL-AF4 hESCs transcriptionally 被告知向对 endothelial 成熟敏感的 hemogenic 先锋区分,由联系到 vascular-endothelial 功能和早造血作用的主人基因的显著 upregulation 思考了。而且,我们报导那 MLL-AF4 表情不是足够的转变导出 hESC 的造血的房间。这个工作说明 hESCs 怎么可以提供唯一的卓见进人的开发并且推进我们理解白血病的熔化基因,知道出生前地产生,调整人的胚胎的造血的说明。 | Clara Bueno Rosa Montes Gustavo J Melen Verdnica Ramos-Mejia Pedro J Real Ver6nica Ayllo'n Laura Sanchez Gertmdis Ligero Inmaculada Gutierrez-Aranda Agustin F Femfindez Mario F Fraga Inmaculada Moreno-Gimeno Deborah Btlrks Maria del Carmen Plaza-Calonge Juan C Rodriguez-Manzaneque Pablo Menendez | 2012 | Cell Research2012，22，6： | 2 |
| 20 | Heavy metal immobilization by chemical amendments in a polluted soil and influence on white lupin growth显示文摘 | Paola C Laura S Pietro M | 2005 | Chemosphere2005，60，： | 1 |
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