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Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors

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The Innovation 2024年第3期5卷 129-137页

作者： Balázs Gyorffy Department of Biophysics Medical SchoolUniversity of Pecs7624 PecsHungary Department of Bioinformatics Semmelweis University1094 BudapestHungary Cancer Biomarker research Group Institute of Molecular Life SciencesHUN-REN Research Centre for Natural Sciences1117 BudapestHungary

Identifying genes with prognostic significance that can act as biomarkers in solid tumors can help stratify patients and uncover novel therapy ***,our goal was to expand our previous ranking analysis of survival-associated genes in various solid tumors to include colon cancer specimens with available transcriptomic and clinical data.A Gene Expression Omnibus search was performed to identify available datasets with clinical data and raw gene expression measurements.A combined database was set up and integrated into our Kaplan-Meier plotter,making it possible to identify genes with expression changes linked to altered *** a demonstration of the utility of the platform,the most powerful genes linked to overall survival in colon cancer were identified using uni-and multivariate Cox regression *** combined colon cancer database includes 2,137 tumor samples from 17 independent *** most significant genes associated with relapse-free survival with a false discovery rate below 1%in colon cancer carcinoma were RBPMS(hazard rate[HR]=2.52),TIMP1(HR=2.44),and COL4A2(HR=2.36).The three strongest genes associated with shorter survival in stage II colon cancer include CSF1R(HR=2.86),FLNA(HR=2.88),and TPBG(HR=2.65).In summary,a new integrated database for colon cancer is presented.A colon cancer analysis subsystem was integrated into our Kaplan-Meier plotter that can be used to mine the entire database(https://***).The portal has the potential to be employed for the identification and prioritization of promising biomarkers and therapeutic target candidates in multiple solid tumors including,among others,breast,lung,ovarian,gastric,pancreatic,and colon cancers.

关键词： colon tumors analysis

The role of gap junctions in cell death and neuromodulation in the retina

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Neural Regeneration research 2021年第10期16卷 1911-1920页

作者： Gergely Szarka Marton Balogh Adam J.Tengolics Alma Ganczer Bela Volgyi Tamas Kovacs-Oller janos szentagothai research centre University of PecsPecsHungary Retinal Electrical Synapses research Group National Brain Research Program(NAP 2.0)Hungarian Academy of SciencesBudapestHungary Department of Experimental Zoology and Neurobiology University of PecsPecsHungary Medical School University of PecsPecsHungary

Vision altering diseases,such as glaucoma,diabetic retinopathy,age-related macular degeneration,myopia,retinal vascular disease,traumatic brain injuries and others cripple many lives and are projected to continue to cause anguish in the foreseeable *** junctions serve as an emerging target for neuromodulation and possible regeneration as they directly connect healthy and/or diseased cells,thereby playing a crucial role in *** they are permeable for macromolecules,able to cross the cellular barriers,they show duality in illness as a cause and as a therapeutic *** this review,we take recent advancements in gap junction neuromodulation(pharmacological blockade,gene therapy,electrical and light stimulation)into account,to show the gap junction’s role in neuronal cell death and the possible routes of rescuing neuronal and glial cells in the retina succeeding illness or injury.

关键词： age-related macular degeneration bystander effect connexin diabetic retinopathy gap junction glaucoma neuromodulation retina retinal disease vision

Cell death and survival following manual and femtosecond laser-assisted capsulotomy in age-related cataract

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International Journal of Ophthalmology(English edition) 2018年第9期11卷 1440-1446页

作者： Andrea Krisztina Siikosd Judit Rapp Diatna Feller Gyorgy Setalo Jr Beata Gaspar Judit E.Pongracz Hajnalka Abraham Zsolt Biro Department of Ophthalmology the University of Pecs Medical School and Clinical CentrePecs 7623Hungary Department of Pharmaceutical Biotechnology Faculty of Pharmacythe University of PecsPecs 7624Hungary janos szentagothai research centre of the university of pecs Pecs 7624Hungary Department of Medical Biology and Central Electron Microscopic Laboratory the University of Pecs Medical SchoolPecs 7624Hungary Optimum Laser centre Budapest 1124Hungary

AIM： To study molecular and morphological changes in lens epithelial cells following femtosecond laser-assisted and manually performed continuous curvilinear capsulotomy（CCC） in order to get information about these methods regarding their potential role in the induction of development of secondary cataract. METHODS： Anterior lens capsules（ALC） were removed from 40 patients with age-related cataract by manual CCC and by femtosecond laser-assisted capsulotomy（FLAC）. Samples removed by manual CCC were assorted in group 1, FLAC samples were classified in group 2. Morphology of lens epithelial cells was examined with light and electron microscopes. Following capsulotomy, expressions of p53, Bcl-2 and cyclin D1 genes were analyzed with reverse transcriptase polymerase chain reaction. Immunohistochemistry was used to detect the pro-apoptotic p53 in the epithelial cells. RESULTS： Light and electron microscopic examination showed that ALC of group 1 contained more degenerating cells following manual CCC than after FLAC. The expression level of p53 was higher after manual than laser-assisted surgery. Immunocytochemistry indicated significantly higher number of cells containing p53 protein in the manual CCC group than following FLAC. Bcl-2 and cyclin D1 gene expression levels were slightly lower following manual CCC than after FLAC, but the difference was not significant. CONCLUSION： Manually removed ALC shows slightly, but not significantly larger damage due to the mechanical stretching and pulling of the capsule than those removed using FLAC.

关键词： capsulotomy capsulorhexis femtosecond laser immunhistology ultrastructure gene expression

Interleukin and interleukin receptor gene polymorphisms in inflammatory bowel diseases susceptibility

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World Journal of Gastroenterology 2014年第12期20卷 3208-3222页

作者： Lili Magyari Erzsebet Kovesdi Patricia Sarlos Andras Javorhazy Katalin Sumegi Bela Melegh Department of Medical Genetics University of Pecs szentagothai research centre 1~(st) Department of Internal Medicine University of Pecs Department of Urology University of Pecs

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), represents a group of chronic inflammatory disorders caused by dysregulated immune responses in genetically predisposed individuals. Genetic markers are associated with disease phenotype and long-term evolution, but their value in everyday clinical practice is limited at the moment. IBD has a clear immunological background and interleukins play key role in the process. Almost 130 original papers were revised including meta-analysis. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but text often do not available for the doctors use these in the clinical practice nowadays. We conducted a systematic review of the current literature on interleukin and interleukin receptor gene polymorphisms associated with IBD, performing an electronic search of PubMed Database from publications of the last 10 years, and used the following medical subject heading terms and/or text words: IBD, CD, UC, interleukins and polymorphisms.

关键词： Inflammatory bowel disease, Crohn’ s disease, Ulcerative colitis, Interleukin, Interleukin receptor, Polymorphisms

Surgical stress and cytoskeletal changes in lens epithelial cells following manual and femtosecond laser-assisted capsulotomy

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International Journal of Ophthalmology(English edition) 2020年第6期13卷 927-934页

作者： ANDrea Krisztina Sükosd Krisztina Szabadfi Edina Szabó-Meleg Beáta Gáspár Pavel Stodulka Gyorgy SétálóJr Róbert Gábriel Miklós Nyitrai Zsolt Biró Hajnalka Abrahám Department of Ophthalmology University of Pecs Medical School and Clinical CentrePecs 7623Hungary Department of Experimental Zoology and Neurobiology University of PecsPecs 7624Hungary Department of Biophysics University of Pecs Medical School and Clinical CentrePecs 7624Hungary janos szentagothai research centre University of PecsPecs 7624Hungary Optimum Laser centre Budapest 1124Hungary Gemini Eye Clinics Zlin 76001Czech Republic Department of Medical Biology and Central Electron Microscopic Laboratory University of Pecs Medical SchoolPecs 7624Hungary

AIM:To study the effect of mechanical stress on the cytoskeleton in lens epithelial cells following conventional phacoemulsification surgery(CPS)and femtosecond laserassisted cataract surgery(FLACS).METHODS:The cytoskeleton of the epithelial cells of the anterior lens capsules(ALC)removed by CPS and FLACS was examined by *** of the intermediate filament,glial fibrillary acidic protein(GFAP),and glutamine synthetase(GS)immunoreactivity were *** order to map the actin network of cells,fluorescently labeled phalloidin was *** samples were examined using confocal laser scanning ***:GFAP expression was visible in a larger number of the epithelial cells after CPS compared to *** CPS sample’s epithelial cells,GFAP immunoreactivity indicated robust morphological *** the actin filaments,the presence of tubular elements connecting epithelial cells,regular actin pattern and marked cortical network after CPS were *** FLACS,the actin cytoskeleton of the epithelial cells remained densely structured,and the tubular elements were undetectable,however,the above-mentioned regular actin pattern and the marked cortical network were ***:The conventional removal of the ALC induces more robust changes of the cytoskeleton of the lens epithelial cells.

关键词： lens epithelial cell cytoskeleton capsulotomy glial fibrillary acidic protein actin

Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions

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World Journal of Gastroenterology 2014年第1期20卷 219-227页

作者： Patricia Sarlos Dalma Varszegi Veronika Csongei Lili Magyari Luca Jaromi Lajos Nagy Bela Melegh 1~(st) Department of Internal Medicine University of Pecs7623 PecsHungary Department of Dermatology Venereology and OncodermatologyUniversity of Pecs7624 PecsHungary Department of Immunology and Biotechnology University of Pecs7624 PecsHungary szentagothai research centre 7624 PecsHungary Department of Medical Genetics University of Pecs7624 PecsHungary Institute of Family Medicine University of Pecs7632 PecsHungary

AIM: To study the inflammatory bowel disease-5 locus (IBD5) and interleukin-23 receptor (IL23R) gene variants in UC patients and test for gene-gene interaction.

关键词： Gene-gene interaction Interleukin-23 receptor gene Inflammatory bowel disease-5 locus Ulcerative colitis Inflammatory bowel disease

Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim janos M.Kanczler Stuart Lanham Andrew Rawlings Marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of Medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon *** composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)*** inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

Immunological changes in different patient populations with chronic hepatitis C virus infection

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World Journal of Gastroenterology 2016年第20期22卷 4848-4859页

作者： Laszlo Szereday Matyas Meggyes Melinda Halasz Julia Szekeres-Bartho Alajos Par Gabriella Par Department of Medical Microbiology and Immunology University of PecsClinical Centre7624 PecsHungary janos szentagothai research centre 7624 PecsHungary First Department of Internal Medicine University of PecsClinical Centre7624 PecsHungary

AIM: To investigate killer inhibitory and activating receptor expression by natural killer(NK), natural killer T-like(NKT-like) and CD8+ T lymphocytes in patients with chronic hepatitis C virus(HCV) infection with elevated and with persistently normal alanine aminotransferase(PNALT).METHODS: The percentage of peripheral blood Treg cells, KIR2DL3, ILT-2, KIR3DL1, CD160, NKG2 D, NKG2 C expressing NK, T and NKT-like cells, cytokine production and NK cytotoxicity were determined by flow cytometry. Twenty-one patients with chronic HCV infection with elevated alanine aminotransferase, 11 HCV carriers with persistently normal alanine aminotransferase and 15 healthy volunteers were enrolled. RESULTS: No significant differences were observed in the percentage of total T, NK or NKT-like cells between study groups. Comparing the activating and inhibitoryreceptor expression by NK cells obtained from HCV carriers with PNALT and chronic HCV hepatitis patients with elevated alanine aminotransferase, NKG2 D activating receptor expression was the only receptor showing a significant difference. NKG2 D expression of NK cells was significantly lower in patients with elevated alanine aminotransferase. The expression of CD160, NKG2 D and NKG2 C activating receptor by CD8+ T cells were significantly lower in patients with chronic HCV hepatitis than in healthy controls and in HCV carriers with PNALT. Plasma TGF-β1 levels inversely correlated with NKG2 D expression by NK cells. In vitro TGF-β1 treatment inhibited NK cells cytotoxic activity and downregulated NKG2 D expression. CD8+ T cells from HCV carriers with PNALT showed significantly elevated expression of CD160, NKG2 D and NKG2 C activating receptors compared to chronic HCV patients with elevated alanine aminotransferase. Enhanced expression of inhibitory KIR2DL3 receptor, and decreased ILT-2 expression on NK cells were also found in chronic hepatitis C patients compared to healthy ***: Our study demonstrated a complex

关键词： Hepatitis C Natural killer cell NKG2D Cytotoxicity Cytokine

Tilted pulse front pumping techniques for efficient terahertz pulse generation

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Light(Science & Applications) 2023年第11期12卷 2291-2308页

作者： Gyorgy Toth Gyula Polonyi janos Hebling university of pecs Pecs 7624Hungary szentagothai research centre Pecs 7624Hungary HUN-REN-PTE High-Field Terahertz research Group Pecs 7624Hungary

Optical rectification of femtosecond laser pulses has emerged as the dominant technique for generating single-and few-cycle terahertz(THz)*** advent of the tilted pulse front pumping(TPFP)velocity matching technique,proposed and implemented two decades ago,has ushered in significant advancements of these THz sources,which are pivotal in the realm of THz pump-probe and material control experiments,which need THz pulses with microjoule energies and several hundred kV/cm electric field ***,these THz sources are poised to play a crucial role in the realization of THz-driven particle accelerators,necessitating millijoule-level pulses with tens of MV/cm electric field *** has enabled the efficient velocity matching in lithium niobate crystals renowned for their extraordinary high nonlinear ***,its adaptation to semiconductor THz sources has resulted in a two-hundred-times enhancement in conversion *** this comprehensive review,we present the seminal achievements of the past two *** expound on the conventional TPFP setup,delineate its scaling limits,and elucidate the novel generation TPFP configurations proposed to surmount these constraints,accompanied by their preliminary ***,we provide an in-depth analysis of the THz absorption,refractive index,and nonlinear coefficient spectra of lithium niobate and widely used semiconductors employed as THz generators,which dictate their suitability as THz *** underscore the far-reaching advantages of tilted pulse front pumping,not only for LN and semiconductor-based THz sources but also for selected organic crystal-based sources and Yb-laserpumped GaP sources,previously regarded as velocity-matched in the literature.

关键词： pumping pulse realization