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Pathophysiological mechanisms of death resistance in colorectal carcinoma

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World Journal of Gastroenterology 2015年第41期21卷 11777-11792页

作者： Ching-Ying Huang linda Chia-Hui Yu Graduate Institute of Physiology National Taiwan University College of Medicine

Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks ofunlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contri-butes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways(i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

关键词： Colon cancer Tumorigenesis Anti-apoptosis Chemores

Case-control study of factors that trigger inflammatory bowel disease flares

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World Journal of Gastroenterology 2014年第15期20卷 4329-4334页

作者： linda A Feagins Ramiz Iqbal Stuart J Spechler VA North Texas Healthcare System DallasTX 75216United States Division of Gastroenterology University of Texas Southwestern Medical CenterDallasTX 75216United States

AIM: To explore the association between inflammatory bowel diseases (IBD) flares and potential triggers.

关键词： Inflammatory bowel diseases, Flare, Non-adherence, Crohn’ s disease, Ulcerative colitis

Irritable bowel syndrome and functional constipation management with integrative medicine: A systematic review

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World Journal of Clinical Cases 2019年第21期7卷 3486-3504页

作者： Liang Dai linda LD Zhong Guang Ji Institute of Digestive Diseases Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China School of Chinese Medicine Hong Kong Baptist UniversityHong KongChina

BACKGROUND Irritable bowel syndrome(IBS)and functional constipation(FC)are two commonly encountered functional gastrointestinal disorders in clinical practice and are usually managed with Western medicines in cooperation with traditional Chinese medicine(TCM)*** clinical practice guidelines(CPGs)have been developed to assist clinicians with their decisions,there are still gaps in management with regard to integrative medicine(IM)*** To comprehensively review the currently available CPGs and to provide a reference for addressing the gaps in IBS and FC *** We searched mainstream English and Chinese databases and collected data from January 1990 to January *** search was additionally enriched by manual searches and the use of publicly available *** on the development method,the guidelines were classified into evidence-based(EB)guidelines,consensus-based(CB)guidelines,and consensus-based guidelines with no comprehensive consideration of the EB(CB-EB)*** regard to the recommendations,the strength of the interventions was uniformly converted to a 4-point grading *** Thirty CPGs met the inclusion criteria and were captured as data extraction *** Western medicine(WM)CPGs were developed as EB *** TCM CPGs and most IM CPGs were identified as CB *** the 2011 IBS and IM CPG was a CB-EB set of *** and peppermint oil for pain,loperamide for diarrhea,and linaclotide for constipation polyethylene glycol and lactulose as osmotic laxatives,bisacodyl and sodium picosulfate as stimulant laxatives,lubiprostone and linaclotide as prosecretory agents,and prucalopride were strongly recommended or recommended in *** interventions were suggested based on pattern differentiation,while the recommendation level was considered to be weak or *** WM CPGs generally provide a comprehensive management algorithm,although there are still s

关键词： Irritable bowel disease Functional constipation Clinical practice guideline Integrative medicine Systematic review

Preconditioners and Electron Density Optimization in Orbital-Free Density Functional Theory

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Communications in Computational Physics 2012年第6期12卷 135-161页

作者： linda Hung Chen Huang Emily A.Carter Program in Applied and ComputationalMathematics Princeton UniversityPrincetonNJ 08544USA Department of Physics Princeton UniversityPrincetonNJ 08544USA Department of Mechanical and Aerospace Engineering and Andlinger Center for Energy and the Environment Princeton UniversityPrincetonNJ 08544USA

Orbital-free density functional theory(OFDFT)is a quantum mechanical method in which the energy of a material depends only on the electron density and ionic *** examine some popular algorithms for optimizing the electron density distribution in OFDFT,explaining their suitability,benchmarking their performance,and suggesting some *** start by describing the constrained optimization problem that encompasses electron density ***,we discuss the line search(including Wolfe conditions)and the nonlinear conjugate gradient and truncated Newton algorithms,as implemented in our open source OFDFT *** finally focus on preconditioners derived from OFDFT energy *** preconditioners are successful for simulation cells of all sizes without regions of low electron-density and for small simulation cells with such regions.

关键词： Density functional theory truncated Newton method conjugate gradient method constrained optimization benchmarks

Exploring behavioral traits over different contexts in four species of Australian funnel-web spiders

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Current Zoology 2023年第6期69卷 766-774页

作者： linda Hernandez Duran David Thomas Wilson Tasmin Lee Rymer College of Science and Engineering James Cook UniversityP.O.Box 6811CairnsQLD 4870Australia Centre for Tropical Environmental and Sustainability Sciences James Cook UniversityCairnsQLD 4870Australia Centre for Molecular Therapeutics Austr alian Institute for Tropical Health and MedicineJames Cook UniversityCairnsQLD 4878Australia

Australian funnel-web spiders are arguably the most venomous spiders in the world,with much research focusing on this aspect of their ***,other aspects related to their life history,ecology and behaviour have been *** the first time,we assessed *** risk-taking behaviour,aggressiveness and activity in the contexts of predation,conspecific tolerance and exploration of a new territory in four species of Australian funnel-web spiders:two are closely related,Hadronyche valida and ***,and two have overlapping distributions but occupy different habitats,*** and Atrax *** also compared behaviors between *** the species level,we found that *** showed consistency in risk-taking behavior when exposed to a predator stimulus,aggressiveness against conspecifics,and exploration of a new *** contrast,in the other species,only *** showed repeatability in the context of exploration of a new *** results suggest that some behavioral traits are likely more flexible than others,and that the repeatability of behaviors may be species-specific in *** we compared species,we found differences in risk-taking behavior and *** study provides novel insights to understanding variation in behavioral traits within and between species of funnel-web spiders,suggesting that some behavioral traits are likely context and/or species dependent,as a result of their evolutionary *** findings provide key insights for understanding the ecological role of behavior and venom deployment in venomous animals,and a greater understanding of behavior in these medically significant and iconic spiders thatareof conservation concern.

关键词： arachnids behavior ecological contexts flexibility mygalomorphae repeatability

In silico docking analysis of beta-defensin 20 against cation channel sperm-associated protein 1–4 to predict its role in the sperm maturation

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Asian Journal of Andrology 2023年第4期25卷 528-532页

作者： Luluk Yunaini linda Erlina Fadilah Fadilah Dwi Ari Pujianto Doctoral Program for Biomedical Sciences Faculty of MedicineUniversitas IndonesiaJakarta 10430Indonesia Department of Medical Biology Faculty of MedicineUniversitas IndonesiaJakarta 10430Indonesia Department of Medical Chemistry Faculty of MedicineUniversitas IndonesiaJakarta 10430Indonesia Bioinformatics Core Facilities Indonesia Medical Education and Research Institute(IMERI)Faculty of MedicineUniversitas IndonesiaJakarta 10430Indonesia

Beta-defensin 20(DEFB20)is widely expressed in the epididymis with gene features involved in epididymal sperm ***,the action mechanism and function of DEFB20 in sperm maturation are still *** of the important roles of beta-defensin is the ion channel *** cation channel sperm-associated protein(CatSper)alpha is an ion channel protein found on the sperm *** study aimed to investigate the interaction between DEFB20 and CatSper1–4 protein in relation to the sperm maturation *** sequences were obtained from the National Center for Biotechnology Information(NCBI).Protein modeling and validation were carried out by using the Robetta modeling server and the Ramachandran plot *** web server was used for the docking *** results revealed a natural interaction between DEFB20 and CatSper1–*** interaction occurred at the cation channel(close to the casein kinase II),ion transport protein,and kinase c phosphorylation of the CatSper1–4 active *** DEFB20 region interacting with CatSper2–4 was the beta-defensin domain,while with CatSper1 was the non-beta-defensin *** on the analysis,DEFB20 may interact with CatSperαsubunits,particularly CatsSper1,to affect ion channel activity during sperm maturation.

关键词： CatSper DEFB20 docking sperm maturation

PAI-1 4G-4G and MTHFR 677TT in non-hepatitis C virus/hepatitis B virus-related liver cirrhosis

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World Journal of Hepatology 2015年第29期7卷 2920-2926页

作者： linda Pasta Francesca Pasta Department of Medicine Clinica Candela

AIM To evaluate the different roles of thrombophiliain patients with and without viral etiology. The thrombophilicgenetic factors （THRGFs）, PAI-1 4G-4G, MTHFR677TT, V Leiden 506Q and prothrombin 20210A,were studied as risk factors in 1079 patients with livercirrhosis （LC）, enrolled from January 2000 to ***： All Caucasian LC patients consecutivelyobserved in a seven year period were included; thepresence of portal vein thrombosis （PVT） and BuddChiari syndrome （BCS） was registered. The differencesbetween the proportions of each THRGF with regardto the presence or absence of viral etiology and thefrequencies of the THRGF genotypes with those predictedin a population by the Hardy-Weinberg equilibriumwere ***： Four hundred and seventeen/one thousandand seventy-six patients （38.6%） showed thrombophilia：217 PAI-1 4G-4G, 176 MTHFR C677TT, 71 V Leidenfactor and 41 prothrombin G20210 A, 84 with morethan 1 THRGF; 350 presented with no viral liver cirrhosis（NVLC） and 729 with, called viral liver cirrhosis （VLC）,of whom 56 patients were hepatitis C virus ＋ hepatitisB virus. PAI-1 4G-4G, MTHFR C677TT, the presence ofat least one TRHGF and the presence of 〉 1 THRGF,were statistically more frequent in patients with NVLC vspatients with VLC： All χ 2 〉 3.85 and P 〈 0.05. Patientswith PVT and/or BCS with at least one TRHGF were189/352 （53.7%）. The Hardy-Weinberg of PAI-1 andMTHFR 677 genotypes deviated from that expectedfrom a population in equilibrium in patients with NVLC（respectively χ 2 = 39.3; P 〈 0.000 and χ 2 = 27.94; P 〈0.05）, whereas the equilibrium was respected in ***： MTHFR 677TT was nearly twofold andPAI-1 4G-4G more than threefold more frequently foundin NVLC vs patients with VLC; the Hardy-Weinbergequilibrium of these two polymorphisms confirms thisdata in NVLC. We suggest that PAI-1 4G-4G and MTHFR677TT could be considered as factors of fibrosis andthrombosis mechanisms, increasing the inflammationresponse, and causing the hepa

关键词： PAI-1 4G-4G MTHFR 677TT V Leiden506Q Prothrombin 20210A Liver cirrhosis Portal veinthrombosis Budd Chiari syndrome Fibrogenesis

Study for the Forming Principle of Logix Gear Tooth Profile and Its Mesh Performance

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厦门大学学报（自然科学版） 2002年第S1期41卷 91-92页

作者： Lee Leckseng linda Lee Singapore Polytechnic Singapore Polytechnic SingaporeSingapore

In recent years, a new type of gear named Logix gea r was developed. Actually, the tooth profile of this new type of gear is composed of lots of micro-segment involute curves, and on the profile, there exist lots of points, which their relative curvatures are equal to zero. This can result in the sliding coefficient smaller between two meshed Logix gears, and the mesh ch aracteristic becomes almost rolling transmission from sliding transmission accor dingly. So, this new type of gear has lots of advantages such as higher contact intensity, longer useful life and can easily realize power transfer of bigger tr ansmission ratio than standard involute gear. Study results showed that the cont act fatigue strength is 3 times larger, the bend fatigue strength is 2.5 times l arger, and the minimum tooth number can be decreased to 3, much smaller than tha t of standard involute gear. In this paper, following studies had been done: 1) The formation principle of Logix gear tooth profile was studied. The theoreti cal models describing the geometrical formations of this type of gear and its re lative Logix rack had been deduced. 2) While cutting a Logix gear, its tooth profile is decided by its normal tooth profile of Logix rack. Besides the basic parameters of standard involute gear, L ogix rack has its own specific parameters such as preliminary pressure angle, re lative pressure angle, and preliminary referential circle radius etc. So, the in fluence of connatural parameters of Logix rack on the tooth profile of Logix gea r had been farther studied. Reasonable selection for these parameters had been d iscussed. 3) Several kinds of transition curves for gear’s tooth profile had been introdu ced, its selection used by Logix gear had been described, and also its mathemati cal description model had been deduced. 4) The mesh theories of Logix gears had been developed. It had been proved that the transmission performance between Logix gears coincides with E-W theorem as that of ord

关键词： Logix gear forming principle mesh performance big transmission ratio

Antigen presentation,autoantibody production,and therapeutic targets in autoimmune liver disease

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Cellular & Molecular Immunology 2021年第1期18卷 92-111页

作者： Andrea Kristina Horst Kingsley Gideon Kumashie Katrin Neumann linda Diehl Gisa Tiegs Institute of Experimental Immunology and Hepatology University Medical Center Hamburg-EppendorfMartinistraBe 52D-20251 HamburgGermany Hamburg Center for Translational Immunology University Medical Center Hamburg-EppendorfMartinistraBe 52D-20251 HamburgGermany

The liver is an important immunological organ that controls systemic *** liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and *** the immune response in homeostasis depends on a healthy and well-toned immunological liver microenvironment,which Is maintained by the crosstalk of liver-resident antigen-presenting cells and intrahepatic and liver-infiltrating *** response to pathogens or autoantigens,tolerance is disrupted by unknown *** parenchymal and nonparenchymal cells exhibit unique antigen-presenting *** presentation of microbial and endogenous lipid-,metabolite-and peptide-derived antigens from the gut via conventional and nonconventional mechanisms can educate intrahepatic immune cells and elicit effector responses or *** of this balance results in autoimmune liver diseases,such as autoimmune hepatitis,primary biliary cholangitis,and primary sclerosing *** the exact etiologies of these autoimmune liver diseases are unknown,it is thought that the disruption of tolerance towards self-antigens and microbial metabolites and lipids,as well as alterations in bile acid composition,may result in changes in effector cell activation and polarization and may reduce or impair protective antiinflammatory regulatory T and B cell ***,the canonical and noncanonical transmission of antigens and antigen:MHC complexes via trogocytosis or extracellular vesicles between different(non)immune cells in the liver may play a role in the induction of hepatic inflammation and ***,we summarize emerging aspects of antigen presentation,autoantibody production,and the application of novel therapeutic approaches in the characterization and treatment of autoimmune liver diseases.

关键词： liver tolerance autoimmune liver disease antigen presentating cell