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1Protective effect of probiotics on intestinal barrier function in malnourished rats after liver transplantation显示文摘BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR)ofPeyer'spatches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts oftranslocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer's patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8 + and γδTCR + lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer's patches, and also slightly restored the alteration of lymphocyte phenotypes. CONCLUSION: Supplementation with probiotics including Bifidobac-terium and Lactobacillus promoted partial restoration of intestinal microflora and improved intestinal barrier function in malnourished rats after liver transplantation with long-term use of antibiotics.Zhi-Gang Ren, Hui Liu, Jian-Wen Jiang, Li Jiang, Hui Chen, Hai-Yang Xie, Lin Zhou and Shu-Sen Zheng Key Laboratory of Combined Multi-organ Transplan- tation, Ministry of Public Health, and Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China and Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China 2011Hepatobiliary & Pancreatic Diseases International2011,10,5:20
2Enteral supplementation with glycyl-glutamine improves intestinal barrier function after liver transplantation in rats显示文摘BACKGROUND:Most patients after liver transplantation (LT) suffer from intestinal barrier dysfunction.Glycyl-glutamine (Gly-Gln) by parenteral supplementation is hydrolyzed to release glutamine,which improves intestinal barrier function in intestinal injury.This study aimed to investigate the effect of GlyGln by enteral supplementation on intestinal barrier function in rats after allogenetic LT under immunosuppressive therapy.METHODS:Twelve inbred Lewis rats were selected randomly as donors,and 24 inbred Brown Norway (BN) rats as recipients of allogenetic LT.The recipients were divided into a control group (Ala,n=12) and an experimental group (Gly-Gln,n=12).In each group,6 normal BN rats were sampled for normal parameters on preoperative day 3.The 6 recipients in the control group received alanine (Ala) daily by gastric perfusion for 3 preoperative days and 7 postoperative days,and the 6 recipients in the experimental group were given Gly-Gln in the same manner.The 12 BN recipients underwent orthotopic LT under sterile conditions after a 3-day fast and were given immunosuppressive therapy for 7 days.They were harvested for sampling on postoperative day 8.The following parameters were assessed:intestinal mucosal protein content,mucosal ultrastructure,ileocecal sIgA content,portal plasma levels of endotoxin and TNF-α,and bacterial translocation.RESULTS:All recipients were alive after LT.On preoperative day 3,all parameters were similar in the two groups.On postoperative day 8,all parameters in the two groups were remarkably changed from those on preoperative day 3.However,compared to the Ala group,supplementation withGly-Gln increased the levels of intestinal mucosal protein and ileocecal sIgA,improved mucosal microvilli,and decreased portal plasma levels of endotoxin and TNF-α as well as bacterial translocation.CONCLUSION:Enteral supplementation with Gly-Gln improved intestinal barrier function after allogenetic LT in rats.Jian-Wen Jiang,Zhi-Gang Ren,Lu-Yan Chen,Li Jiang,Hai-Yang Xie,Lin Zhou and Shu-Sen Zheng Key Laboratory of Combined Multi-organ Transplantation,Ministry of Public Health Department of Hepatobiliary and Pancreatic Surgery,First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China 2011Hepatobiliary & Pancreatic Diseases International2011,10,4:17
3Alginate oligosaccharide-induced intestinal morphology, barrier function and epithelium apoptosis modifications have beneficial effects on the growth performance of weaned pigs显示文摘Background: Alginate oligosaccharide(AOS), produced from alginate by alginate lyase-mediated depolymerisation, is a potential substitute for antibiotics and possesses growth-enhancing effects. Nevertheless, the mechanisms by which AOS regulates porcine growth remain to be elucidated. Therefore, we investigated the AOS-mediated changes in the growth performance of weaned pigs by determining the intestinal morphology, barrier function,as well as epithelium apoptosis.Methods: Twenty-four weaned pigs were distributed into two groups(n = 12) and received either a basal diet(control group) or the same diet supplemented with 100 mg/kg AOS. On d 15, D-xylose(0.1 g/kg body weight)was orally administrated to eight randomly selected pigs per treatment, and their serum and intestinal mucosa samples were collected 1 h later.Results: Our results showed that inclusion of AOS in the diet for 2 wk increased(P < 0.05) the average daily body weight gain in weaned pigs. Notably, AOS supplementation ameliorated the intestinal morphology and barrier function, as suggested by the enhanced(P < 0.05) intestinal villus height, secretory immunoglobulin A content and goblet cell counts. Compared to the control group, AOS ingestion both decreased(P < 0.05) the total apoptotic percentage and increased(P < 0.05) the proportion of S phase in the intestinal epithelial cells. Furthermore, AOS not only up-regulated(P < 0.05) the B-cell lymphoma-2(BCL2) transcriptional level but also down-regulated(P < 0.05) the B-cell lymphoma-2-associated X protein(BAX), cysteinyl aspartate-specific proteinase-3(caspase-3) and caspase-9 transcriptional levels in the small intestine.Conclusions: In summary, this study provides evidence that supplemental AOS beneficially affects the growth performance of weaned pigs, which may result from the improved intestinal morphology and barrier function,as well as the inhibited enterocyte death, through reducing apoptosis via mitochondria-dependent apoptosis.Jin Wan Jiao Zhang Daiwen Chen Bing Yu Xiangbing Mao Ping Zheng Jie Yu Junqiu Luo Jun He 2018Journal of Animal Science and Biotechnology2018,9,4:10
4Systems pharmacology approach reveals protective mechanisms of Jian-Pi Qing-Chang decoction on ulcerative colitis显示文摘BACKGROUND Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM. AIM To investigate the protective mechanisms of JPQC decoction on UC based on systems pharmacology approach. METHODS We performed systems pharmacology to predict the active ingredients, the matched targets, and the potential pharmacological mechanism of JPQC on UC. In vivo, we explored the effects of JPQC in a colitis model induced by dextran sulfate sodium. In vitro, we adopted the bone marrow-derived macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the underlying mechanisms and effects of JPQC on UC under TNF-α stimulation. RESULTS Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC. Protein-protein interaction networks were established to identify the underlying therapeutic targets of JPQC on UC. Based on enrichment analyses, we proposed our hypothesis that JPQC might have a protective effect on UC via the NF-κB/HIF-1α signalling pathway. Subsequent experimental validation revealed that treatment with TNFα activated the NF-κB/HIF-1α signalling pathway in BMDMs, thereby damaging the epithelial barrier permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The findings were also confirmed in a dextran sulfate sodium-induced colitis model. CONCLUSION JPQC could improve the mucosal inflammatory response and intestinal epithelial barrier function via the NF-κB/HIF-1α signalling pathway, which provides new perspectives on the pharmaceutical development and clinical practice of TCM.You-Lan Chen Yi-Yuan Zheng Yan-Cheng Dai Ya-Li Zhang Zhi-Peng Tang 2019World Journal of Gastroenterology2019,25,21:9
5Combined probiotic bacteria promotes intestinal epithelial barrier function in interleukin-10-gene-deficient mice显示文摘AIM:To investigate the protective effects of combinations of probiotic(Bifico)on interleukin(IL)-10-genedeficient(IL-10 KO)mice and Caco-2 cell monolayers.METHODS:IL-10 KO mice were used to assess the benefits of Bifico in vivo.IL-10 KO and control mice received approximately 1.5×108 cfu/d of Bifico for 4 wk.Colons were then removed and analyzed for epithelial barrier function by Ussing Chamber,while an ELISA was used to evaluate proinflammatory cytokines.The colon epithelial cell line,Caco-2,was used to test the benefit of Bifico in vitro.Enteroinvasive Escherichia coli(EIEC)and the probiotic mixture Bifico,or single probiotic strains,were applied to cultured Caco-2 monolayers.Barrier function was determined by measuring transepithelial electrical resistance and tight junction protein expression.RESULTS:Treatment of IL-10 KO mice with Bifico partially restored body weight,colon length,and epithelial barrier integrity to wild-type levels.In addition,IL-10 KO mice receiving Bifico treatment had reduced mucosal secretion of tumor necrosis factor-αand interferon-γ,and attenuated colonic disease.Moreover,treatment of Caco-2 monolayers with Bifico or singlestrain probiotics in vitro inhibited EIEC invasion and reduced the secretion of proinflammatory cytokines.CONCLUSION:Bifico reduced colon inflammation in IL-10 KO mice,and promoted and improved epithelialbarrier function,enhanced resistance to EIEC invasion,and decreased proinflammatory cytokine secretion.Chen-Zhang Shi Hong-Qi Chen Yong Liang Yang Xia Yong-Zhi Yang Jun Yang Jun-Dong Zhang Shu-Hai Wang Jing Liu Huan-Long Qin 2014World Journal of Gastroenterology2014,20,16:9
6Probiotic mixture VSL#3:An overview of basic and clinical studies in chronic diseases显示文摘Probiotics are known as“live microorganisms”and have been proven to have a health effect on hosts at the proper dose.Recently,a kind of probiotic mixture including eight live bacterial strains,VSL#3,has attracted considerable attention for its combined effect.VSL#3 is the only probiotic considered as a kind of medical food;it mainly participates in the regulation of the intestinal barrier function,including improving tight junction protein function,balancing intestinal microbial composition,regulating immune-related cytokine expression and so on.The objective of this review is to discuss the treatment action and mechanism for the administration of VSL#3 in chronic diseases of animals and humans(including children).We found that VSL#3 has a therapeutic or preventive effect in various systemic diseases per a large number of studies,including digestive systemic diseases(gastrointestinal diseases and hepatic diseases),obesity and diabetes,allergic diseases,nervous systemic diseases,atherosclerosis,bone diseases,and female reproductive systemic diseases.Fang-Shu Cheng Dan Pan Bing Chang Min Jiang Li-Xuan Sang 2020World Journal of Clinical Cases2020,8,8:7
7The impact of codon 54 variation in intestinal fatty acid binding protein gene on the pathogenesis of diabetes mellitus in Chinese显示文摘Noninsulindependentdiabetesmelitus(NIDDM)isnowconsideredtobeacomplexdiseaseresultingfromgeneticandenvironmentalfactors.Mutat...项坤三 郑泰山 贾伟平 孙多奇 丁炜 陆俊茜 唐峻岭 1999Chinese Medical Journal1999,,2:4
8Human small intestine is capable of restoring barrier function after short ischemic periods显示文摘AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and 120 min of reperfusion(R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose(L) and rhamnose(R). Plasma concentrations of citrulline,an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions( TJs),by plasma marker for enterocytes damage(I-FABP) and analyzed by electron microscopy(EM) using lanthanum nitrate as an electrondense marker.RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia(30 I) followed by 30 min of reperfusion(30 R) compared to control(0.75 ± 0.10 vs 0.20 ± 0.09,P < 0.05). At 120 min of reperfusion(120 R),ratio's normalized(0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points(correlation: 0.467,P < 0.01). TJs staining shows distortion of staining at 30 I. An intact lining of TJs was again observed at 30 I120 R. Electron microscopy analysis revealed disrupted TJs after 30 I with paracellular leakage of lanthanum nitrate,which restored after 30 I120 R. Furthermore,citrulline concentrations closely paralleled the histological perturbations during intestinal IR.CONCLUSION This study directly correlates histological data with intestinal permeability tests,revealing that the human gut has the ability of to withstand short episodes of ischemia,with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.Dirk HSM Schellekens Inca HR Hundscheid Claire AJI Leenarts Joep Grootjans Kaatje Lenaerts Wim A Buurman Cornelis HC Dejong Joep PM Derikx 2017World Journal of Gastroenterology2017,23,48:4
9Endoplasmic reticulum stress-induced apoptosis in intestinal epithelial cells:a feed-back regulation by mechanistic target of rapamycin complex 1(mTORC1)显示文摘Background: Endoplasmic reticulum(ER) stress is associated with multiple pathological processes of intestinal diseases. Despite a critical role of mechanistic target of rapamycin complex 1(m TORC1) in regulating cellular stress response, the crosstalk between m TORC1 and ER stress signaling and its contribution to the intestinal barrier function is unknown.Results: In the present study, we showed that intestinal epithelial cells(IEC-6) incubated with tunicamycin led to caspase-3-dependent apoptotic cell death. The induction of cell death was accompanied by activation of unfolded protein response as evidenced by increased protein levels for Bi P, p-IRE1α, p-e IF2α, p-JNK, and CHOP. Further study demonstrated that tunicamycin-induced cell death was enhanced by rapamycin, a specific inhibitor of m TORC1.Consistently, tunicamycin decreased transepithelial electrical resistance(TEER) and increased permeability of the cells. These effects of tunicamycin were exacerbated by m TORC1 inhibitor.Conclusions: Taken together, the data presented here identified a previously unknown crosstalk between an unfold protein response and m TORC1 signaling in the intestinal epithelium. This feed-back loop regulation on ER stress signaling by m TORC1 is critical for cell survival and intestinal permeability in epithelial cells.Yun Ji Xuan Luo Ying Yang Zhaolai Dai Guoyao Wu Zhenlong Wu 2018Journal of Animal Science and Biotechnology2018,9,3:3
10Dietary supplementation of Bacillus subtilis influenced intestinal health of weaned pigs experimentally infected with a pathogenic E. coli显示文摘Background: There is growing evidence to support the beneficial effects of supplementing direct-fed microbials(DFM) on performance, health status, and immune responses of weaned pigs. Therefore, the objective of this study was to investigate dietary supplementation of Bacillus subtilis(DSM 25841) on growth performance, diarrhea, gut permeability and immunity of weaned pigs experimentally infected with a pathogenic F-18 Escherichia coli(E. coli).Results: The F18 E. coli infection reduced(P < 0.05) growth performance and intestinal villi height, whereas increased(P < 0.05) diarrhea and transcellular and paracellular permeability in the jejunum compared with non-challenged control. Supplementation of Bacillus subtilis linearly enhanced average daily gain of E. coli infected pigs from d 0 to 5 post-inoculation(PI)(P < 0.05) and d 0 to 11 PI(P = 0.058). Supplementation of high dose of Bacillus subtilis reduced(P < 0.05) both transcellular and paracellular permeability on d 5 and d11 PI compared with the E. coli infected pigs fed with control diet. E. coli infection up-regulated(P < 0.05)the m RNA expression of SLC5 A10(soluble carrier family 5 member 10) and MUC2(mucin 2) on d 5 PI, but down-regulated(P < 0.05) expression of SLC5 A10, MUC2, and CLDN1 on d 11 PI in jejunal mucosa when pigs were fed with the control diet. Supplementation of Bacillus subtilis linearly up-regulated(P < 0.05) the m RNA expression of CFTR and ZO1 on d 5 PI and SLC5 A10 and MUC2 on d 11 PI in jejunal mucosa of E. coli infected pigs. In addition, E. coli infection increased(P < 0.05) the m RNA expression of several immune genes(IL1 A, IL1 B, and IL7 on d 5 PI, and IL1 B, IL6, IL7, and TNF on d 11 PI) in the ileal mucosa of weaned pigs. Inclusion of Bacillus subtilis to control diet linearly down-regulated gene expression of IL1 A on d 5 PI(P = 0.07) and IL6 on d 11 PI(P < 0.05) in ileal mucosa of E. coli infected pigs.Conclusions: Supplementation of Bacillus subtilis(DSM 25841) enhanced growth rate and improved gut barrier function of weaned pigs experimentally infected with a pathogenic E. coli.Kwangwook Kim Yijie He Xia Xiong Amy Ehrlich Xunde Li Helen Raybould Edward R.Atwill Elizabeth A.Maga Jens JΦrgensen Yanhong Liu 2019Journal of Animal Science and Biotechnology2019,10,4:3
11Hypoxia preconditioning protects Ca^(2+)-ATPase activation of intestinal mucosal cells against R/I injury in a rat liver transplantation model显示文摘AIM To investigate the effect of ischaemia and reperfusion(I/R) injury on the Ca^(2+)-ATPase activation in the intestinal tissue of a rat autologous orthotopic liver transplantation model and to determine if hypoxia preconditioning(HP) therapy induces HIF-1α to protect rat intestinal tissue against I/R injury.METHODS Rats received non-lethal hypoxic preconditioning therapy to induce HIF-1α expression. We used an autologous orthotopic liver transplantation model to imitate the I/R injury in intestinal tissue. Then, we detected the microstructure changes in small intestinal tissues, Ca^(2+)-ATPase activity, apoptosis, and inflammation within 48 h postoperatively. RESULTS HIF-1α expression was significantly increased in intestinal tissue at 12 h postoperatively in rats that were exposed to a hypoxic environment for 90 min compared with a non-HP group(HP vs AT, P = 0.0177). Pathological analysis was performed on the intestinal mucosa cells, and the cells in the HP group appeared healthier than the cells in the AT group. The Ca^(2+)-ATPase activity in the small intestinal cells in the AT group was significantly lower after the operation, and the Ca^(2+)-ATPase activity in the HP group recovered faster than that in the AT group at 6 h postoperatively(HP vs AT, P = 0.0106). BCL-2 expression in the HP group was significantly higher than that in the AT group at 12 h postoperatively(HP vs AT P = 0.0010). The expression of the inflammatory factors NO, SOD, IL-6, and TNF-α was significantly lower in the HP group than in the AT group.CONCLUSION Hypoxia-induced HIF-1α could protect intestinal mucosal cells against mitochondrial damage after I/R injury. HP could improve hypoxia tolerance in small intestinal mucosal cells and increase Ca^(2+)-ATPase activity to reduce the apoptosis of and pathological damage to intestinal cells. HP could be a useful way to promote the earlier recovery of intestinal function after graft procedure.Zhi-Peng Ji Yuan-Xin Li Bao-Xu Shi Zhuo-Nan Zhuang Jing-Yan Yang Sen Guo Xiao-Zhou Xu Ke-Sen Xu Hai-Lin Li 2018World Journal of Gastroenterology2018,24,3:3
12Role of intestinal barrier in pathogenesis of pigment gallstone in a guinea pig model显示文摘BACKGROUND: The function of the intestinal barrier has drawn more and more attention from researchers in recent years for its important role in many diseases such as burns, wounds, and pancreatitis. In our experimental studies on pigment gallstone, we found potential relationships between the function of the intestinal barrier and pigment gallstone formation. This study was undertaken to investigate the possible action and mechanism of the function of the intestinal barrier in the pathogenesis of pigment gallstone. METHODS: Eighty guinea pigs were divided into a normal group (CON), a pigment gallstone group (PS) and an intestinal mucosa protection group (GLN). Normal forage, pigment gallstone-forming forage and pigment gallstoneforming forage with supplemental intestinal mucosa protector (glutamine) were given to each group. In the gallstone-forming rate, morphology of intestinal mucosa, intestinal permeability, serum endotoxin and biliaryβ-glucuronidase were assessed after 8 weeks. RESULTS: The rate of gallstone-formation was 73.9% in the PS group. Damage of intestinal mucosa, endotoxemia (from 77±43×106 EU/L to 1367±525×l06 EU/L, P<0.01) and increased activity of biliaryβ-glucuronidase (endogenousβ-glucuromdase from 122.1±39.5 to 209.8±47.5 Fishman Unit, P<0.01, and exogenous p-glucuronidase from 573.5±476.9 to 2206.6±983.9 Fishman Unit, P<0.01) were observed in the PS group compared with the CON group. The rate gallstone-formation decreased significantly to 44.4% and the other indices except P-glucuronidase were lower in the GLN group than in the PS group. CONCLUSIONS: The function of the intestinal barrier is correlated with pigment gallstone formation. Dysfunction of the intestinal barrier function may promote pigment gallstone formation through bacterial translocation, endotoxemia, and biliaryβ-glucuronidase.2006Hepatobiliary & Pancreatic Diseases International2006,5,3:3
13Effects of Zhenren Yangzang Decoction Combined with Modified Shenling Baizhu Powder on Immune Function and Intestinal Microecology of Diarrhea Patients with Deficiency and Cold Syndrome显示文摘OBJECTIVE: To observe the effects of Zhenren Yangzang Decoction combined with modified Shenling Baizhu Powder on the immune function and intestinal microecology of diarrhea patients with deficiency and cold syndrome. METHODS: A total of 60 diarrhea patients with deficiency and cold syndrome were randomly divided into observation group and control group, with 30 cases in each group. The control group was treated with conventional western medicine. The observation group was given the treatment of Zhenren Yangzang Decoction combined with modified Shenling Baizhu Powder on the basis of the same treatment for 4 weeks. The clinical symptoms, fecal flora and immunoglobulin content of the 2 groups were observed and the clinical efficacy was evaluated. RESULTS: After treatment, the symptoms scores of fecal diarrhea, aversion to cold, cold limbs, loss of appetite, cold and painful waist and knee, abdominal fullness, abdominal distension and abdominal pain, and intestinal bacilli contents were significantly decreased(P < 0.05). The contents of lactobacillus, bifidus bacilli, IgG, IgM and IgA were significantly increased(P < 0.05), and the improvement of the above indexes in the observation group was significantly better than that in the control group(P < 0.05). The total effective rate after treatment in the observation group was 93.3%, which was significantly higher than 73.3% of the control group(P < 0.05). CONCLUSION: The treatment of diarrhea patients with deficiency and cold syndrome with Zhenren Yangzang Decoction and modified Shenling Baizhu Powder can effectively improve the intestinal micro-ecological environment, improve the immune function of patients and promote the rapid recovery of patients.张然 2018World Journal of Integrated Traditional and Western Medicine2018,4,4:2
14Cystic fibrosis transmembrane conductance regulator functional evaluations in a G542X+/-IVS8Tn:T7/9 patient with acute recurrent pancreatitis显示文摘BACKGROUND Acute recurrent pancreatitis(ARP)is characterized by episodes of acute pancreatitis in an otherwise normal gland.When no cause of ARP is identifiable,the diagnosis of'idiopathic'ARP is given.Mutations in the cystic fibrosis transmembrane conductance regulator(CFTR)gene increase the risk of ARP by 3-to 4-times compared to the general population,while cystic fibrosis(CF)patients present with a 40-to 80-times higher risk of developing pancreatitis.CASE SUMMARY In non-classical CF or CFTR-related disorders,CFTR functional tests can help to ensure a proper diagnosis.We applied an individualized combination of standardized and new CFTR functional bioassays for a patient referred to the Verona CF Center for evaluation after several episodes of acute pancreatitis.The CFTR genotype was G542X+/-with IVS8Tn:T7/9 polymorphism.The sweat(Cl-)values were borderline.Intestinal current measurements were performed according to the European Cystic Fibrosis Society Standardized Operating Procedure.Recent nasal surgery for deviated septum did not allow for nasal potential difference measurements.Lung function and sputum cultures were normal;azoospermia was excluded.Pancreas divisum was excluded by imaging but hypoplasia of the left hepatic lobe was detected.Innovative tests applied in this case include sweat rate measurement by image analysis,CFTR function in monocytes evaluated using a membrane potential-sensitive fluorescent probe,and the intestinal organoids forskolin-induced swelling assay.CONCLUSION Combination of innovative CFTR functional assays might support a controversial diagnosis when CFTR-related disorders and/or non-classical CF are suspected.Sara Caldrer Gabriella Bergamini Angela Sandri Silvia Vercellone Luca Rodella Angelo Cerofolini Francesco Tomba Filippo Catalano Luca Frulloni Mario Buffelli Gloria Tridello Hugo de Jonge Baroukh Maurice Assael Claudio Sorio Paola Melotti 2019World Journal of Clinical Cases2019,7,22:2
15Intestinal genetic inactivation of caspase-8 diminishes migration of enterocytes显示文摘AIM: To verify the hypothesis that caspase-8(Casp8), which regulates cellular apoptosis and necroptosis, is critically involved in enterocyte migration.METHODS: Casp8-silenced Caco2 cells were used in migration assays. In addition, enterocyte-specific Casp8 heterozygous(Casp8+/?int) or homozygous knockout mice(Casp8?int) were generated by crossing genetically modified mice carrying lox P recombination sites in intron 2 and 4 of the murine Casp8 gene with transgenic animals expressing a cre-transgene under control of the villin promoter in a pure C57/BL6 genetic background. The nucleoside analog Brd U was injected i.p. in male Casp8+/?int and Casp8?int animals 4 h, 20 h, or 40 h before performing morphometric studies. Locations of anti-Brd U-immunostained cells(cellmax) in at least 50 hemi-crypts of 6 histoanatomically distinct intestinal mucosal regions were numbered and extracted for statistical procedures. For the mice cohort(n = 28), the walking distance of enterocytes was evaluated from cellmax within crypt(n = 57), plateau(n = 19), and villus(n = 172) positions, resulting in a total of 6838 observations. Data analysis was performed by fitting a three-level mixed effects modelto the data.RESULTS: In cell culture experiments with Caco2 cells, Casp8 knockdown efficiency mediated by RNA interference on Casp8 transcripts was 80% controlled as determined by Western blotting. In the scratch assay, migration of Casp8-deleted Caco2 cells was significantly diminished when compared with controls(Casp8?scramble and Caco2). In Brd U-labeled Casp8?int mice, cellmax locations were found along the hemi-crypts in a lower position than it was for Casp8+/?int or control(cre-negative) animals. Statistical data analysis with a three-level mixed effects model revealed that in the six different intestinal locations(distinct segments of the small and large intestine), cell movement between the three mice groups differed widely. Especially in duodenal hemi-crypts, enterocyte movement was different between the groups. At 20 h, duodenal cellmax location was significantly lower in Casp8?int(25.67 ± 2.49) than in Casp8+/?int(35.67 ± 4.78; P < 0.05) or control littermates(44.33 ± 0.94; P < 0.01).CONCLUSION: C a s p 8- d e p e n d e n t m i g ra t i o n o f enterocytes is likely involved in intestinal physiology and inflammation-related pathophysiology.Elke Kaemmerer Paula Kuhn Ursula Schneider Min Kyung Jeon Christina Klaus Miriam Schiffer Danika Weisner Christian Liedtke J?rg J?kel Lieven Nils Kennes Ralf-Dieter Hilgers Norbert Wagner Nikolaus Gassler 2015World Journal of Gastroenterology2015,21,15:1
16Effects of Lactobacillus Microecologics on Production Performance, Immune Function and Intestinal Microflora of Egg Chicks显示文摘[Objective]The paper was to study the effects of lactobacillus microecologics on production performance,immune function and intestinal microflora of egg chicks.[Method]Totally 18001-day-old chicks of Hyline brown were randomly divided into three groups,four repeats each group and 150 chicks each repeat.The chicks in control group were supplied with basic diet,and those in experimental groups I and II were supplied with the basic diet added with 100 and 150 g/t microecologics,respectively.[Result]Compared with the control group,the daily gain of egg chicks in experimental group II after 7 weeks was increased by 3.67%(P<0.05),and the feed conversion ratio was significantly reduced by 0.05(P<0.05);the thymus indexes in experimental groups I and II were significantly improved by 4.95%and 5.94%(P<0.05),and the spleen indexes were significantly improved by 3.32% and 4.36% compared with the control group(P<0.05).The index of bursa of fabricius in experimental group II was extremely improved by 9.66%compared with the control group(P<0.01).Meantime,experimental group II extremely improved the number of living lactobacillus in caecum of egg chicks(P<0.01),and extremely reduced the number of Escherichia coli in caecum(P<0.01).[Conclusion]Lactobacillus microecologics are beneficial to the improvement of production performance,immune function and intestinal flora of egg chicks.The optimal addition amount in the feed of chicks is 150 g/t.Xiao Jianshe Pan Huiqing Zhang Yanda 2019Animal Husbandry and Feed Science2019,11,3:0
17Effect of small intestinal submucosa on islet recovery and function in vitro culture显示文摘BACKGROUND: The ability to maintain isolated human islet preparation in tissue culture has recently been adopted by most islet transplant centers to improve the safety and practicality of islet transplantation. However, maintaining islet viability and recovery remains a challenge in clinical setting. Extracellular matrix (ECM) is one of the most important components of islet microenvironment. The reconstruction of the cell-matrix relationship seems to be effective in improving the loss of differentiated islet structure and function. Small intestinal submucosa ( SIS ) , a naturally occurring ECM, has been investigated to be able to promote wound healing, tissue remodeling, and cell growth. The purpose of this study was to evaluate the recovery and function of isolated rat pancreatic islets after in vitro culture with SIS. METHODS: Pancreatic islets were isolated from Wistar rats by using standard surgical procurement followed by intra-ductal collagenase distension, mechanical dissociation, and EuroFicoll purification. Groups of purified islets were cultured in plates which were coated with multilayer SIS (SIS-treated group) or without ( standard cultured group) for 7 days and 14 days in standard islet culture conditions of RP-MI 1640 tissue culture media in humidified atmosphere containing 95% air and 5% CO2 at 37 ℃. The mean recovery of islets after the culture period was determined by sizing duplicate counts of a known volume and their viability was assessed by static incubation with low glucose (2.7 mmol) , high glucose (16.7 mmol) and high glucose solution supplemented with 50 μm 3-isobutyl-1-methylxanthine (IB-MX) solution. RESULTS: After 7 days and 14 days of in vitro tissue culture, the SIS-treated group showed a significantly higher recovery compared with those cultured under standard conditions. The recovery in the SIS-treated group was about two times of the control group cultured in standard conditions after 14 days culture. In the SIS-treated group, there was no statistically difference between the short and long periods of culture ( 95. 8 ± 1.0% vs. 90. 8±1. 5% , P > 0.05). During incubation in high glucose (16.7 mmol) solution, there was a 2-3 fold increase in insulin secretion from both groups, but the SIS-treated group showed a higher increase than the standard cultured group after 14-day culture (20.7 ±1.1 mU/L vs. 11. 8 ±1.1 mU/L, P < 0. 05). When islets were placed in the high glucose solution supplemented with IBMX, the stimulated insulin response in the SIS-treated group was higher than that in the standard cultured group in spite of the duration of the culture. The stimulation index of the SIS-treated group was about 2-3 times of the standard cultured group. In addition , after a long period of culture, the stimulation index of the SIS-treated group was statistically equivalent with that of the short period of culture (9.5 ±0.2 vs. 10.2 ±1.2, P>0.05). CONCLUSIONS: The co-culture of isolated rat islets with native sheet-like SIS can provide an excellent extracellular matrix, possible biotrophic and growth factors that promote the recovery and subsequent function of islets after in vitro tissue culture. In view of results of this study and rapid degradation of SIS in vitro, future studies will investigate the extended duration of culture and the effect of SIS on islets in vitro.2005Hepatobiliary & Pancreatic Diseases International2005,4,4:0
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