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Diagnostic and prognostic potential of tissue and circulating long non-coding rNAs in colorectal tumors

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World Journal of Gastroenterology 2019年第34期25卷 5026-5048页

作者： Orsolya Galamb barbara K barták Alexandra Kalmár Zsófia b Nagy Krisztina A Szigeti Zsolt Tulassay Peter Igaz béla molnár Molecular Medicine research Group Hungarian Academy of SciencesBudapest H-1088Hungary 2nd Department of Internal Medicine Semmelweis UniversityBudapest H-1088Hungary

Long non-coding rNAs(lncrNAs)are members of the non-protein coding rNA family longer than 200 *** participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CrC).As CrC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is *** are promising candidates as they are involved in carcinogenesis,and certain lncrNAs(e.g.,CCAT1,CrNDE,CrCAL1-4)show altered expression in adenomas,making them potential early diagnostic *** addition to being useful as tissue-specific markers,analysis of circulating lncrNAs(e.g.,CCAT1,CCAT2,blaCAT1,CrNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic *** review article aims to describe the origin,structure,and functions of lncrNAs and to discuss their contribution to CrC ***,our purpose is to summarise lncrNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CrC.

关键词： Long non-coding rNA Colorectal cancer Colorectal adenoma Circulating long non-coding rNAs Exosome biomarker Diagnostic marker Prognostic marker

Epithelial toll-like receptor 9 signaling in colorectal inflammation and cancer: Clinico-pathogenic aspects

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World Journal of Gastroenterology 2013年第26期19卷 4119-4126页

作者： István Fri Ferenc Sipos Tiana M Germann Alexandra Kalmár Zsolt Tulassay béla molnár Gyrgyi Mzes 2nd Department of Internal Medicine Semmelweis University Faculty of Medicine Semmelweis University Molecular Medicine research Unit Hungarian Academy of Sciences

Toll-like receptors (TLrs) recognize specific motifs which are frequently present in bacteria, fungi, prokaryotes and viruses. Amongst TLrs, TLr9 can be activated by such bacterial or viral DNA fragments, immunoglobulin-DNA complexes or synthetic oligonucleotides, which all contain unmethylated cytosineguanine nucleotide sequences (CpGs). Emerging data indicate that TLr9 signaling has a role in, and may influence, colorectal carcinogenesis and colonic inflammation. CpGs are classified into three groups according to their influence on both the antigen-specific humoraland cellular immunity, and the production of type 1 interferons and proinflammatory cytokines. TLr9 activation via CpGs may serve as a new therapeutic target for several cancerous and various inflammatory conditions. Due to its probable anti-cancer effects, the application possibilities of TLr9-signaling modulation may be extremely diverse even in colorectal tumors. In this review we aimed to summarize the current knowledge about TLr-signaling in the pathogenesis and therapy of inflammatory bowel diseases and colorectal cancer. Due to the species-specific differences in TLr9 expression, however, one must be careful in translating the animal model data into the human system, because of the differences between CpG-oligodeoxynucleotide-responsive cells. TLr9 agonist DNA-based immunomodulatory sequences could also represent a promising therapeutic alternative in systemic inflammatory conditions and chronic colonic inflammations as their side effects are not significant.

关键词： Toll-like receptor 9 Synthetic oligodeoxy-nucleotide sequences DNA-based immunomodulatory sequences Colorectal cancer Inflammatory bowel diseases

Physiological and pathological role of local and immigrating colonic stem cells

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World Journal of Gastroenterology 2012年第4期18卷 295-301页

作者： Ferenc Sipos Gábor Valcz béla molnár 2nd Department of Internal Medicine Semmelweis University Molecular Medicine research Unit Hungarian Academy of Sciences

The latest avenue of research is revealing the existence of and role for the colonic stem cells in the physiological renewal of the mucosa and in pathological circumstanc- es where they have both positive and negative effects. In the case of human colon, different levels of stem cell compartments exist. First, the crypt epithelial stem cells, which have a role in the normal crypt epithelial cell dynamics and in colorectal carcinogenesis. Close to the crypts, the second layer of stern cells can be found; the local subepithelial stem cell niche, including the pericryptic subepithelial myofibroblasts that regulate the epithelial cell differentiation and have a crucial role in cancer progression and chronic inflammation-related fibrosis. The third level of stem cell compartment is the immigrating bone-marrow-derived stem cells, which have an important role in wound healing after severe mucosal inflammation, but are also involved in cancer invasion. This paper focuses on stem cell biology in the context of physiological and pathological processes in the human colon.

关键词： Colon Mesencyhmal stem cells bone marrow Myofibroblast Fibrosis Colorectal cancer Para-thyroid hormone Transforming growth factor-β

regulatory T cells in inflammatory bowel diseases and colorectal cancer

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World Journal of Gastroenterology 2012年第40期18卷 5688-5694页

作者： Gyrgyi Mzes béla molnár Ferenc Sipos 2nd Department of Internal Medicine Semmelweis University Molecular Medicine research Unit Hungarian Academy of Sciences

regulatory T cells(T regs) are key elements in immunological *** number of T regs may alter in both peripheral blood and in colonic mucosa during pathological *** local cellular,microbiological and cytokine milieu affect immunophenotype and function of T *** box P3+ T regs function shows altered properties in inflammatory bowel diseases(IbDs).This alteration of T regs function can furthermore be observed between Crohn's disease and ulcerative colitis,which may have both clinical and therapeutical *** mucosal inflammation may also influence T regs function,which together with the intestinal bacterial flora seem to have a supporting role in colitis-associated colorectal carcinogenesis.T regs have a crucial role in the immunoevasion of cancer cells in sporadic colorectal ***,their number and phenotype correlate closely with the clinical outcome of the disease,even if their contribution to carcinogenesis has previously been *** knowledge of the clinical relationship between IbD and colitis-associated colon cancer,and the growing number of immunological aspects encompassing sporadic colorectal carcinogenesis,the molecular and cellular links amongst T regs,regulation of the inflammation,and cancer development are still not well *** this paper,we aimed to review the current data surrounding the role of T regs in the pathogenesis of IbD,colitis-associated colon cancer and sporadic colorectal cancer.

关键词： regulatory T cells Forkhead box P3 Inflam-matory bowel diseases Colitis-associated colon cancer Colorectal cancer

Changes of the cytokine profile in inflammatory bowel diseases

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World Journal of Gastroenterology 2012年第41期18卷 5848-5861页

作者： Gyrgyi Mzes béla molnár Zsolt Tulassay Ferenc Sipos 2nd Department of Internal Medicine Semmelweis University1088 BudapestHungary Molecular Medicine research Unit Hungarian Academy of Sciences1051 BudapestHungary

Cytokines are indispensable signals of the mucosaassociated immune system for maintaining normal gut *** imbalance of their profile in favour of inflammation initiation may lead to disease states,such as that is observed in inflammatory bowel diseases(IbD).Although Crohn's disease(CD) is often described as a prototype of T-helper 1-type diseases,and ulcerative colitis(UC) is traditionally viewed as a T-helper 2-mediated condition,the classic paradigm,which categorises cytokines into pro-and anti-inflammatory groups,has recently been *** inflammation regulatory pathways may not be mutually exclusive as individual cytokines can have diverse and even opposing functions in various clinical and immunological *** the less there are many common immunological responses in IbD that are mediated by *** they regulate and influence the development,course and recurrence of the inflammatory process,the concrete pathogenic role of these small signaling molecules is sometimes not unambiguous in the subtypes of the *** aim is to review the current information about pro-and anti-inflammatory effects of traditionally studied and recently discovered cytokines in the pathogenesis of UC and *** better understanding of their production and functional activity may lead to the development of new therapeutic modalities.

关键词： Ulcerative colitis Crohn's disease Interleu-kin-33 Tumor necrosis factor-like factor Interleukin-8 Interleukin-35 Interleukin-25 Interleukin-4 Tumornecrosis factor ligand superfamily member 14

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World Journal of Gastroenterology 2016年第47期22卷 10325-10340页

作者： Orsolya Galamb Alexandra Kalmár barbara Kinga barták árpád V Patai Katalin Leiszter bálint Péterfia barnabás Wichmann Gábor Valcz Gábor Veres Zsolt Tulassay béla molnár Molecular Medicine research Group Hungarian Academy of Sciences 2~(nd) Department of Internal Medicine Semmelweis University 1~(st) Department of Paediatrics Semmelweis University

AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CrC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFrP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CrC patients using bisulfite-specific PCr followed by methylation-specific high resolution melting(MS-HrM) analysis. m rNA expression of age-related "epigenetic clock" genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CrC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture *** Fifty-seven age-related Cp G sites including hypermethylated PPP1r16 b, SFrP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CrC and normal tissues(P rmal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFrP1, SYNE1 and hypomethylated CEMIP, SPATA18(P rM analysis, the SFrP1 promoter region was significantly hypermethylated in CrC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P lation of SFrP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P rrelated with significantly increased S

关键词： DNA methylation Aging Colorectal cancer Adenoma Epigenetic drift Epigenetic clock Secreted frizzled related protein 1

How dopamine tunes parvalbumin interneurons in the hippocampus:new experimental observations in Alzheimer's disease

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Neural regeneration research 2025年第5期20卷 1405-1406页

作者： Livia la barbera Paraskevi Krashia Annalisa Nobili Department of Medicine and Surgery UniversitàCampus Bio-Medico di RomaViaÁlvaro del PortilloRomeItaly Department of Experimental Neurosciences IRCCS Santa Lucia FoundationVia del Fosso di FioranoRomeItaly Department of Science and Technology for Sustainable Development and One Health UniversitàCampus Bio-Medico di RomaViaÁlvaro del PortilloRomeItaly

Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc *** is cha racterized by featured histological alterations including amyloid-beta (Ab) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.

关键词： Alzheimer alterations dopamine

Knotting ligands to control metal coordination geometry

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Science China Chemistry 2025年第2期68卷 403-404页

作者： Fabien b.L.Cougnon Department of Chemistry and Nanoscience Centre University of JyväskyläJyväskyläFinland

Zinc is a metal of particular importance for life[1].It is the most abundant transition metal in biological systems after iron and contributes both structural and catalytic roles to many cellular *** properties of Zn^(Ⅱ),unlike those of any other first-row transition metal ions,explain its biological *** to its filled d-shell orbitals,Zn^(Ⅱ) is redox-stable,has a ligand-field energy stabilization of zero and,consequently,no typical coordination number and *** metalloproteins exploit these features to carry a broad range of chemical reactions in mild *** metalloenzymes,unsaturated ZnII centres often act as redox-stable Lewis *** protein backbone provides a highly preorganized environment around the metal centre and accompanies the changes in coordination geometry occurring as substrate transformation proceeds,thereby modulating the metal reactivity.

关键词： coordination geometry centre

Characterization and source apportionment of volatile organic compounds in Hong Kong:A 5-year study for three different archetypical sites

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Journal of Environmental Sciences 2025年第5期151卷 424-440页

作者： Yuchen Mai Vincent Cheung Peter K.K.Louie Kenneth Leung Jimmy C.H.Fung Alexis K.H.lau Donald r.b.lake Dasa Gu Division of Environment and Sustainability The Hong Kong University of Science and TechnologyHong Kong 999077China Environmental Protection Department Hong Kong 999077China Environment and Ecology bureau Hong Kong 999077China Department of Chemistry University of CaliforniaIrvine 92617USA

Initial success has been achieved in Hong Kong in controlling primary air pollutants,but ambient ozone levels kept increasing during the past three *** organic compounds(VOCs)are important for mitigating ozone pollution as its major *** study analyzed VOC characteristics of roadside,suburban,and rural sites in Hong Kong to investigate their compositions,concentrations,and source *** showthat the TVOC concentrations were 23.05±13.24,12.68±15.36,and 5.16±5.48 ppbv for roadside,suburban,and rural sites between May 2015 to June 2019,*** using Positive Matrix Factorization(PMF)model,six sources were identified at the roadside site over five years:Liquefied petroleum gas(LPG)usage(33%–46%),gasoline evaporation(8%–31%),aged air mass(11%–28%),gasoline exhaust(5%–16%),diesel exhaust(2%–16%)and fuel filling(75–9%).Similarly,six sources were distinguished at the suburban site,including LPG usage(30%–33%),solvent usage(20%–26%),diesel exhaust(14%–26%),gasoline evaporation(8%–16%),aged air mass(4%–11%),and biogenic emissions(2%–5%).At the rural site,four sources were identified,including aged airmass(33%–51%),solvent usage(25%–30%),vehicular emissions(11%–28%),and biogenic emissions(6%–12%).The analysis further revealed that fuel filling and LPG usage were the primary contributors to OFP and OH reactivity at the roadside site,while solvent usage and biogenic emissions accounted for almost half of OFP and OH reactivity at the suburban and rural sites,*** findings highlight the importance of identifying and characterizing VOC sources at different sites to help policymakers develop targeted measures for pollution mitigation in specific areas.

关键词： Volatile organic compounds Positive matrix factorization Source apportionment Ozone formation