The endothelin family has been related with several pathological diseases including cardiovascular disorders, hypertension and cancer. However, little is known about endothelin system in early stages of colorectal can...The endothelin family has been related with several pathological diseases including cardiovascular disorders, hypertension and cancer. However, little is known about endothelin system in early stages of colorectal cancer and there are no studies evaluating differences in proximal and distal colon segments. To deepen in this issue, we have studied the endothelin’s family gene and protein expression in normal mice and early stage of a mice model of Azoxymethane (AOM) and Dextran Sodium Sulphate (DSS) induced colorectal cancer in proximal and distal segments. Additionally, using nonlinear microscopy (NLM) techniques, we have characterized collagen changes in early stages of cancer disease development. In the present study, we have found significant differential gene expression and protein localization between these colon regions, which allow us to hypothesize a new role for the ET-2 as an early marker of colon cancer development.展开更多
BACKGROUND Anti-tumor necrosis factor α(TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microb...BACKGROUND Anti-tumor necrosis factor α(TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal healing.AIM To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium(DSS) colitis.METHODS Eighty C57 BL/6 mice were divided into four groups: "No DSS", "No DSS + antiTNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and"DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score(Disease Activity Index), colon length and histology. Bacteria such as Bacteroides, Clostridiaceae, Enterococcaceae and Fecalibacterium prausnitzii(F. prausnitzii) were evaluated by quantitative PCR.Type 1 helper T lymphocytes(Th1), type 17 helper T lymphocytes(Th17) and CD4+ regulatory T lymphocytes(Treg) distributions in the mesenteric lymph node(MLN) were studied by flow cytometry.RESULTS Bacteria associated with a healthy state(i.e., such as Bacteroides, Clostridiaceae and F. prausnitzii) decreased during colitis and increased in course of anti-TNFαtreatment. Conversely, microorganisms belonging to Enterococcaceae genera,which are linked to inflammatory processes, showed an opposite trend.Furthermore, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase(day 5 of the colitis) in Treg cells and a consequent decrease(day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune features of untreated colitic mice. "No D展开更多
Inflammatory bowel diseases(IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeu...Inflammatory bowel diseases(IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary noninvasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography,discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.展开更多
AIM:To investigate the effects of the free radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decandioate(IAC) in the dextran sodium sulphate(DSS) experimental model of ulcerative colitis.METHODS:Colit...AIM:To investigate the effects of the free radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decandioate(IAC) in the dextran sodium sulphate(DSS) experimental model of ulcerative colitis.METHODS:Colitis was induced in Sprague Dawley male rats by administration of 5% DSS in drinking water.IAC(30 mg/kg,lipophilic or hydrophilic form) was administered daily(orally or ip) for 6 d until sacrifice.Colonic damage was assessed by means of indirect(Disease Activity Index score) and direct measures(macroscopic and microscopic scores) and myeloperoxidase(MPO)activity.Neutrophil infiltration within the tissue and glutathione S-transferase activity were also investigated.RESULTS:DSS-induced colitis impaired body weight gain and markedly increased all inflammatory parameters.Six-day treatment with lipophilic IAC significantly reduced intestinal damage caused by inflammation,induced a down-regulation in MPO activity(0.72 ± 0.12 and 0.45 ± 0.12 with lipophilic IAC po and ip,respectively,vs 1.10 ± 0.27 in untreated DSS colitis animals) and minimized DSS-induced neutrophil infiltration,while hydrophilic IAC administered orally did not ameliorate DSS-induced damage.CONCLUSION:These results support the hypothesis that reactive oxygen metabolites contribute to inflammation and that the radical scavenger IAC has therapeutic potential in inflammatory bowel disease.展开更多
文摘The endothelin family has been related with several pathological diseases including cardiovascular disorders, hypertension and cancer. However, little is known about endothelin system in early stages of colorectal cancer and there are no studies evaluating differences in proximal and distal colon segments. To deepen in this issue, we have studied the endothelin’s family gene and protein expression in normal mice and early stage of a mice model of Azoxymethane (AOM) and Dextran Sodium Sulphate (DSS) induced colorectal cancer in proximal and distal segments. Additionally, using nonlinear microscopy (NLM) techniques, we have characterized collagen changes in early stages of cancer disease development. In the present study, we have found significant differential gene expression and protein localization between these colon regions, which allow us to hypothesize a new role for the ET-2 as an early marker of colon cancer development.
文摘BACKGROUND Anti-tumor necrosis factor α(TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal healing.AIM To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium(DSS) colitis.METHODS Eighty C57 BL/6 mice were divided into four groups: "No DSS", "No DSS + antiTNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and"DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score(Disease Activity Index), colon length and histology. Bacteria such as Bacteroides, Clostridiaceae, Enterococcaceae and Fecalibacterium prausnitzii(F. prausnitzii) were evaluated by quantitative PCR.Type 1 helper T lymphocytes(Th1), type 17 helper T lymphocytes(Th17) and CD4+ regulatory T lymphocytes(Treg) distributions in the mesenteric lymph node(MLN) were studied by flow cytometry.RESULTS Bacteria associated with a healthy state(i.e., such as Bacteroides, Clostridiaceae and F. prausnitzii) decreased during colitis and increased in course of anti-TNFαtreatment. Conversely, microorganisms belonging to Enterococcaceae genera,which are linked to inflammatory processes, showed an opposite trend.Furthermore, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase(day 5 of the colitis) in Treg cells and a consequent decrease(day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune features of untreated colitic mice. "No D
基金Supported by The European Union Seventh Framework Programme for Research and Technological Development(FP 7)grant EUTRAIN(European Translational Training for Autoimmunity and Immune Manipulation NetworkNo.289903 to Gohar F
文摘Inflammatory bowel diseases(IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary noninvasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography,discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.
基金Supported by A Grant from the University of Bologna (Ricerca Fondamentale Orientata)
文摘AIM:To investigate the effects of the free radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decandioate(IAC) in the dextran sodium sulphate(DSS) experimental model of ulcerative colitis.METHODS:Colitis was induced in Sprague Dawley male rats by administration of 5% DSS in drinking water.IAC(30 mg/kg,lipophilic or hydrophilic form) was administered daily(orally or ip) for 6 d until sacrifice.Colonic damage was assessed by means of indirect(Disease Activity Index score) and direct measures(macroscopic and microscopic scores) and myeloperoxidase(MPO)activity.Neutrophil infiltration within the tissue and glutathione S-transferase activity were also investigated.RESULTS:DSS-induced colitis impaired body weight gain and markedly increased all inflammatory parameters.Six-day treatment with lipophilic IAC significantly reduced intestinal damage caused by inflammation,induced a down-regulation in MPO activity(0.72 ± 0.12 and 0.45 ± 0.12 with lipophilic IAC po and ip,respectively,vs 1.10 ± 0.27 in untreated DSS colitis animals) and minimized DSS-induced neutrophil infiltration,while hydrophilic IAC administered orally did not ameliorate DSS-induced damage.CONCLUSION:These results support the hypothesis that reactive oxygen metabolites contribute to inflammation and that the radical scavenger IAC has therapeutic potential in inflammatory bowel disease.
