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Bacteroides fragilis Supernatant Extracts Enriched in Phenylacetic Acid Induce a Cytotoxic Effect in Mammalian Cells

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Advances in Microbiology 2015年第10期5卷 730-736页

作者： Laís S.Falcao Eduardo N.F.Antunes Eliane O.Ferreira Heidi Pauer maria teresa v.romanos Rossiane C.vommaro Sérgio H.Seabra Daniela S.Alviano Celuta S.Alviano Antonio Jorge R.da Silva Leandro A.Lobo Regina maria C.P.Domingues Departamento de Ciências Básicas Pólo Universitário de Nova FriburgoUniversidade Federal FluminenseNova FriburgoBrasil Instituto de Microbiologia Prof.Paulo de Góes Universidade Federal do Rio de JaneiroRio de JaneiroBrasil Instituto de Biofísica Carlos Chagas Filho Universidade Federal do Rio de JaneiroRio de JaneiroBrasil Centro Universitário Estadual da Zona Oeste—UEZO Rio de JaneiroBrasil Instituto de Pesquisa Produtos Naturais Universidade Federal do Rio de JaneiroRio de JaneiroBrasil

Bacteroides species are nearly half of the fecal flora community and some are host symbionts crucial to host nutrition and systemic immunity. Among Bacteroides species B. fragilis strains are considered to be the opportunistic ones, being the most isolated anaerobic bacteria in clinical samples. Cell-free supernatants of 65 B. fragilis strains were assayed and they were capable of inducing vacuolating phenotype on vero cells lineage. The supernatant of the Bacteroides fragilis ATCC 23745 strain was elicited to have the strongest vacuolating effect on vero cells monolayers and peritoneal macrophages. Some drastic cell alterations were observed, such as a general disorganization of cytoplasm and chromatin condensation, evidencing cell death. By transmission electron microscopy it was confirmed that the vacuoles observed were, in fact, swollen mitochondria. An immunocytochemical assay, TUNEL, was used to confirm this hypothesis and showed that vero cells and peritoneal macrophages were dying by apoptotic process after exposition of B. fragilis cell-free supernatant. Physical analysis of the apoptotic factor has revealed properties similar to short-chain fatty acids. After gas chromatography and mass spectrometry analysis, phenylacetic acid (PA) was characterized as the major compound present in the most purified active fraction. We believe that the PA is responsible for the pro-apoptotic effect elicited by the supernatant of B. fragilis cultures.

关键词： Bacteroides fragilis vacuolization Apoptosis vero cells Lineage Peritoneal Macrophages Phenylacetic Acid

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Non-celiac gluten sensitivity:Time for sifting the grain

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World Journal of Gastroenterology 2015年第27期21卷 8221-8226页

作者： Luca Elli Leda Roncoroni maria teresa Bardella Center for Prevention and Diagnosis of Celiac Disease Gastroenterology and Endoscopy Unit Department of Pathophysiology and Transplantation Università degli Studi di Milano. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico

In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism(autoimmune in celiac disease and Ig E-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity(NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.

关键词： Celiac disease Gluten Gluten-relateddisorders Gluten sensitivity Non-celiac gluten sensitivity

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CRISPR/Cas system: An emerging technology in stem cell research

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World Journal of Stem Cells 2019年第11期11卷 937-956页

作者： maria teresa valenti Michela Serena Luca Dalle Carbonare Donato Zipeto Department of Medicine Section of Internal Medicine DUniversity of VeronaVerona 37134Italy Department of Biochemistry University of OxfordOxford OX13QUUnited Kingdom Department of Neurosciences Biomedicine and Movement SciencesLaboratory of Molecular BiologyVerona 37134Italy

The identification of new and even more precise technologies for modifying and manipulating the genome has been a challenge since the discovery of the DNA double *** ability to modify selectively specific genes provides a powerful tool for characterizing gene functions,performing gene therapy,correcting specific genetic mutations,eradicating diseases,engineering cells and organisms to achieve new and different functions and obtaining transgenic animals as models for studying specific *** regularly interspaced short palindromic repeats(CRISPR)/Cas9 technology has recently revolutionized genome *** application of this new technology to stem cell research allows disease models to be developed to explore new therapeutic *** possibility of translating new systems of molecular knowledge to clinical research is particularly appealing for addressing degenerative *** this review,we describe several applications of CRISPR/Cas9 to stem cells related to degenerative *** addition,we address the challenges and future perspectives regarding the use of CRISPR/Cas9 as an important technology in the medical sciences.

关键词： Gene editing CRISPR/Cas9 Stem cells Degenerative diseases

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Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer:A focus on biological mechanisms and therapeutic opportunities

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World Journal of Gastroenterology 2023年第18期29卷 2764-2783页

作者： Federico Selvaggi teresa Catalano Rossano Lattanzio Roberto Cotellese Gitana maria Aceto Department of Surgical ASL2 Lanciano-Vasto-ChietiOspedale Clinicizzato SS Annunziata of ChietiChieti 66100Italy Department of Clinical and Experimental Medicine University of MessinaMessina 98125Italy Department of Innovative Technologies in Medicine&Dentistry University“G.d’Annunzio”Chieti-PescaraChieti 66100Italy Department of Medical Oral and Biotechnological SciencesUniversity“G.d’Annunzio”Chieti-PescaraChieti 66100Italy villa Serena Foundation for Research Villa Serena-Del Dott.L.PetruzziCittàSant’Angelo 65013PescaraItaly Department of Medical Oral and Biotechnological Sciences“G.d’Annunzio”University of Chieti-PescaraChieti 66100Italy

The liver is the most common site of metastases in patients with colorectal *** liver metastases(CRLMs)are the result of molecular mechanisms that involve different cells of the liver *** aberrant activation of Wingless/It(Wnt)/β-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium,but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymalepithelial transition *** liver microenvironment,metastatic cells can also survive and adapt through dormancy,which makes them less susceptible to pro-apoptotic signals and *** of CRLMs is challenging due to its variability and *** in surgery and oncology have been made in the last decade and a pivotal role for Wnt/β-catenin pathway has been recognized in *** the state of art,there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may *** this review,current knowledge on the involvement of Wnt signaling in the development of CRLMs was *** addition,an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.

关键词： Wingless/It/β-catenin signaling Colorectal cancer Epithelial-mesenchymal transition/mesenchymal-epithelial transition Liver metastasis Markers Surgical and non-surgical therapies

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Role of autophagy in bone and muscle biology

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World Journal of Stem Cells 2016年第12期8卷 396-398页

作者： maria teresa valenti Luca Dalle Carbonare Monica Mottes Department of Medicine Section of Internal Medicine D University of Verona Department of Neurological Biomedical and Movement Sciences Section of Biology and Genetics University of Verona

Autophagy in eukaryotic cells is a constitutive process and functions as a homeostatic mechanism; it is up-regulated in response to specific stress stimuli such as starvation, hypoxia and as oxidative stress. In addition to playing a crucial role in adaptive responses to different stimuli, autophagy is also required for intracellular quality control. This second aspect is important to prevent the activation of pathological processes. Autophagy also plays a central role in cellular development and differentiation because it is involved in the regulation of energetic balance. This final aspect is critical for maintaining proper bone and muscle function as well as to prevent any pathological changes. Therefore, identifying new molecular targets involved in autophagy is critical to assure a good quality of life.

关键词： Autophagy Bone Muscle

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Ectopic expression of the osteogenic master gene RUNX2 in melanoma

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World Journal of Stem Cells 2018年第7期10卷 78-81页

作者： maria teresa valenti Luca Dalle Carbonare Monica Mottes Department of Medicine University of Verona Department of Neurosciences Biomedicine and Movement Sciences University of Verona

The transcription factor RUNX2 is the osteogenic master gene expressed in mesenchymal stem cells during osteogenic commitment as well as in pre-osteoblasts and early ***,RUNX2 is also ectopically expressed in melanoma and other *** melanoma(MM)is a highly metastatic skin *** incidence of MM has increased considerably in the past *** expression levels and mutation rates of genes such as BRAF,KIT,NRAS,PTEN,P53,TERT and MITF are higher in melanoma than in other solid ***,transcription factors can affect cellular processes and induce cellular transformation since they control gene ***,several studies have identified alterations in RUNX2 *** particular,the regulation of KIT by RUNX2 and the increased expression of RUNX2 in melanoma specimens have been ***,whose transformation results in melanoma,arise from the neural crest and therefore show"stemness"***2 plays an important role in the re-activation of the MAPK and PI-3K/AKT pathways,thus endowing melanoma cells with a high metastatic *** melanoma,the most frequent metastatic sites are the lung,liver,brain and lymph *** addition,bone metastatic melanoma has been ***,studies focusing on RUNX2may contribute to the identification of an appropriate oncotarget in melanoma.

关键词： RUNX2 Mesenchymal stem cells Epitelial mesenchymal transition Bone Melanoma

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Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第20期25卷 2524-2538页

作者： Michele Barone maria teresa viggiani Giuseppe Losurdo mariabeatrice Principi Alfredo Di Leo Gastroenterology Section Department of Emergency and Organ Transplantation University of Bari Aldo Moro

BACKGROUND Neoangiogenesis is one of the key pathogenetic mechanisms in hepatocellular carcinoma (HCC). Modulation of the renin-angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) seems to be a possible adjuvant therapy for HCC, due to the antiangiogenic and anti-fibrogenic activity of these drugs. AIM To elucidate the role of ARBs and ACE-Is in HCC. METHODS We performed an electronic search of the literature using the most accessed online databases (PubMed, Cochrane library, Scopus and Web of Science), entering the query terms "angiotensin-converting enzyme inhibitors" OR "ACE inhibitors" OR "ACE-I" AND "hepatocarcinoma*" OR "hepatocellular carcinoma;moreover "angiotensin II type 1 receptor blockers" OR "ARBs" AND "hepatocarcinoma*" OR "hepatocellular carcinoma". Eligibility criteria were:(1) prospective or retrospective clinical studies;(2) epidemiological studies;and (3) experimental studies conducted in vivo or in vitro. Abstracts, conference papers, and reviews were excluded a priori. We limited our literature search to articles published in English, in peer-reviewed *** Thirty-one studies were selected. Three interventional studies showed that ACEIs had a significant protective effect on HCC recurrence only when used in combination with vitamin K or branched chain aminoacids, without a significant increase in overall survival. Of six retrospective observational studies, mainly focused on overall survival, only one demonstrated a prolonged survival in the ACE-Is group, whereas the two that also evaluated tumor recurrence showed conflicting results. All experimental studies displayed beneficial effects of RAS inhibitors on hepatocarcinogenesis. Numerous experimental studies, conducted either on animals and cell cultures, demonstrated the anti-angiogenetic and antifibrotic effect of ACE-Is and ARBs, thanks to the suppression of some cytokines such as vascular endothelial growth factor

关键词： Cirrhosis Renin Angiotensin Survival Cancer prevention Hepatocarcinoma

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Lesson from an intriguing case of cryoglobulinemia

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World Journal of Gastroenterology 2013年第2期19卷 304-306页

作者： Michele Barone Raffaele Licinio Annabianca Amoruso maria teresa viggiani Angela maria vittoria Larocca Alfredo Di Leo Department of Emergency and Organ Transplantation University of Bari70100 BariItaly Department of Biomedical Science and Human Oncology University of Bari70100 BariItaly

Cryoglobulinemia is a pathological condition usually associated with hepatitis C virus(HCv) chronic liver disease and less commonly with autoimmune or lymphoproliferative *** possible association of cryoglobulinemia with hepatitis B virus(HBv) infection is not widely *** our patient,serum negativity for HCv markers initially led us to consider two other causes of *** disorders were excluded on the basis of hematological studies,while serum markers for active HBv infection were ***,the detection of HCv RNA in the cryocrit,even in the absence of anti-HCv antibodies suggested a pathogenetic role of HCv in this case of *** "first level" tests for HCv in the serum do not completely exclude HCv involvement in the pathogenesis of *** of the cryoprecipitate is always essential for diagnosis.

关键词： Cryocrit Hepatitis B virus Hepatitis C virus Myelodysplastic disorders Cryoglobulinemia

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Risk factors associated with the development of ischemic colitis

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World Journal of Gastroenterology 2010年第36期16卷 4564-4569页

作者： Joaquín Cubiella Fernández Luisa Núez Calvo Elvira González vázquez maria Jesús García García maria teresa Alves Pérez Isabel Martínez Silva Javier Fernández Seara Department of Gastroenterology Complexo Hospitalario de Ourense32005 OurenseSpain Department of Internal Medicine Complexo Hospitalario de Ourense32005 OurenseSpain Department of Internal Medicine Fundación Pública Hospitalaria de Verín32600 VerinSpain Research Support Unit Complexo Hospitalario de Orense32005 OurenseSpain Biostatistic Unit University of Santiago de Compostela15703 Santiago de CompostelaSpain

AIM:To ascertain the role of cardiovascular risk factors,cardiovascular diseases,standard treatments and other diseases in the development of ischemic colitis(IC).METHODS:A retrospective,case-control study was designed,using matched data and covering 161 incident cases of IC who required admission to our hospital from 1998 through *** was diagnosed on the basis of endoscopic findings and diagnostic or compatible *** were randomly chosen from a cohort of patients who were admitted in the same period and required a colonoscopy,excluding those with diagnosis of *** were matched with controls(ratio 1:2),by age and sex.A conditional logistic regression was ***:A total of 483 patients(161 cases,322 con-trols)were included;mean age 75.67±10.03 years,55.9%*** principal indications for colonos-copy in the control group were lower gastrointestinal hemorrhage(35.4%),anemia(33.9%),abdominal pain(19.9%)and diarrhea(9.6%).The endoscopic findings in this group were hemorrhoids(25.5%),diverticular disease(30.4%),polyps(19.9%)and colorectal cancer(10.2%).The following variables were associated with IC in the univariate analysis:arterial hypertension(P= 0.033);dyslipidemia(Pve drugs(P=0.023);angiotensin-converting enzyme inhibitors;(P=0.018);calcium channel antagonists(P=0.028);and acetylsalicylic acid(ASA)(Pvariables were independently associated with the development of IC:diabetes mellitus[odds ratio(OR)1.76,95%confidence interval(CI):1.001-3.077,P=0.046];dyslipidemia(OR 2.12,95%CI:1.26-3.57,P=0.004);heart failure(OR 3.17,95%CI:1.31-7.68,P=0.01);peripheral arterial disease(OR 4.1,95%CI:1.32-12.72,P=0.015);treatment with digoxin(digitalis)(OR 0.27,95%CI:0.084-0.857,P=0.026);and ASA(OR 1.97,95%CI:1.16-3.36,P=0.012).CONCLUSION:The development of an episode of IC was independently associat

关键词： Ischemic colitis Diabetes mellitus Dyslipidemia Acetylsalicylic acid Peripheral arterial disease Digoxin

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Plasma betatrophin levels in patients with liver cirrhosis

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World Journal of Gastroenterology 2015年第37期21卷 10662-10668页

作者： maria teresa Arias-Loste maria teresa García-Unzueta Susana Llerena Paula Iruzubieta Angela Puente Joaquín Cabezas Carmen Alonso Antonio Cuadrado José Antonio Amado Javier Crespo Emilio Fábrega Gastroenterology and Hepatology Unit Marqués de Valdecilla University HospitalInstituto de Investigación Sanitaria ValdecillaAvenida Valdecilla s/n 39008 Santander Cantabria Spain Endocrinology Unit Marqués de Valdecilla University HospitalInstituto de Investigación Sanitaria Valdecilla Avenida Valdecilla s/n 39008 Santander Cantabria Spain

AIM: To investigate the plasma levels of betatrophin in patients with ***: Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic,or histological criteria were *** severity of cirrhosis was classified according to Pugh's modification of Child's classification and MELD score. Insulin resistance(IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched *** blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay(DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were vely. The normal values were between 2 and17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA(Aviscera Bioscience). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility werevels were significantly increased in patients with cirrhosis compared with those in healthy subjects(P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B(Pve correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification(r = 0.53; P verall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin(r= 0.39; P ved, as well as an inverse correlation between betatrophin and albumin(r =-0.41; P ver, insulin

关键词： Liver cirrhosis Betatrophin Insulin resistance Bet

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