Publications by authors named "Huan-Long Qin"

46 Publications

Impact of probiotics supplement on the gut microbiota in neonates with antibiotic exposure: an open-label single-center randomized parallel controlled study.

World J Pediatr 2021 Aug 31;17(4):385-393. Epub 2021 Jul 31.

Department of Pediatrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Middle Yanchang Road, Shanghai, China.

Background: Antibiotics, a common strategy used for neonatal infection, show consistent effect on the gut microbiota of neonates. Supplementation with probiotics has become increasingly popular in mitigating the loss of the gut microbiota. However, no clear consensus recommending the use of probiotics in the infection of neonates currently exists. This study examined the effects of probiotics on the gut microbiota of infectious neonates when used concurrently with or during the recovery period following antibiotic therapy.

Methods: Fifty-five full-term neonates diagnosed with neonatal infections were divided into the following groups: NI (no intervention, antibiotic therapy only), PCA (probiotics used concurrently with antibiotics), and PAA (probiotics used after antibiotics). The NI group received antibiotic treatment (piperacillin-tazobactam) for 1 week and the PCA group received antibiotic treatment together with probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) for 1 week. The PAA group received antibiotic treatment for 1 week followed by probiotics for 1 week. Fecal samples were collected at four time nodes: newborn, 1 week, 2 weeks, and 42 days after birth. The composition of the gut microbiota was determined by the high-throughput sequencing of 16S rRNA amplicons.

Results: Antibiotic exposure was found to dramatically alter gut microbiota, with a significant decrease of Bifidobacterium and Lactobacillus. The use of probiotics did not restore the overall diversity of the gut microbiota. However, using probiotics simultaneously with the antibiotics was found to be beneficial for the gut microbiota as compared to delaying the use of probiotics to follow treatment with antibiotics, particularly in promoting the abundance of Bifidobacterium.

Conclusions: These results suggest that the early use of probiotics may have a potential ability to remodel the gut microbiota during recovery from antibiotic treatment. However, further study is required to fully understand the long-term effects including the clinical benefits.
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http://dx.doi.org/10.1007/s12519-021-00443-yDOI Listing
August 2021

Helios serves as a suppression marker to reduce regulatory T cell function in pancreatic cancer patients.

Immunol Res 2021 Jun 6;69(3):275-284. Epub 2021 May 6.

Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

Destabilizing and reprogramming regulatory T (Treg) cells have become a potential strategy to treat tumor. Mounting evidence indicates that the transcription factor Helios is required for the stable differentiation of Treg lineage. Hence, we investigated whether Helios suppression could be a potential treatment option for pancreatic cancer patients. We found that Helios cells were predominantly in Foxp3 Treg cells. By contrast, Foxp3 Treg cells can be Helios or Helios, but the level of Foxp3 expression was significantly higher in HeliosFoxp3 Treg cells than in HeliosFoxp3 Treg cells. Resected pancreatic tumors were highly enriched with both HeliosFoxp3 Treg cells and HeliosFoxp3 Treg cells. Also, the proportion of Helios cells in total Foxp3 Treg cells was significantly higher in peripheral blood mononuclear cells (PBMCs) of patients than in PBMCs of healthy controls and further increased in patient tumors. Using shRNA, we knocked down Helios expression without significant downregulation of Foxp3. After Helios knockdown, CD4CD25CD127 Treg cells presented significantly lower levels of TGF-β secretion, lower levels of IL-10 secretion, and higher levels of IFN-γ secretion. In addition, Helios shRNA-transfected CD4CD25CD127 Treg cells presented lower capacity to inhibit CD4CD25CD127 T conventional cell proliferation than control shRNA-transfected CD4CD25CD127 Treg cells. Of note, CD4CD25CD127 Treg cells from pancreatic cancer patients demonstrated higher TGF-β expression and higher suppression capacity than the cells from healthy controls. Overall, these results suggest that in pancreatic cancer patients, Helios may serve as a candidate to suppress Treg function, which could be used as a target to treat pancreatic cancer.
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http://dx.doi.org/10.1007/s12026-021-09200-9DOI Listing
June 2021

SET1A-Mediated Mono-Methylation at K342 Regulates YAP Activation by Blocking Its Nuclear Export and Promotes Tumorigenesis.

Cancer Cell 2018 07 28;34(1):103-118.e9. Epub 2018 Jun 28.

Shanghai Tenth People's Hospital of Tongji University, School of Medicine and School of Life Science and Technology, Tongji University, Shanghai 200072, China. Electronic address:

YAP, a key effector of Hippo pathway, is activated by its translocation from cytoplasm to nucleus to regulate gene expression and promote tumorigenesis. Although the mechanism by which YAP is suppressed in cytoplasm has been well-studied, how the activated YAP is sequestered in the nucleus remains unknown. Here, we demonstrate that YAP is a nucleocytoplasmic shuttling protein and its nuclear export is controlled by SET1A-mediated mono-methylation of YAP at K342, which disrupts the binding of YAP to CRM1. YAP mimetic methylation knockin mice are more susceptible to colorectal tumorigenesis. Clinically, YAP K342 methylation is reversely correlated with cancer survival. Collectively, our study identifies SET1A-mediated mono-methylation at K342 as an essential regulatory mechanism for regulating YAP activity and tumorigenesis.
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http://dx.doi.org/10.1016/j.ccell.2018.06.002DOI Listing
July 2018

Analysis of fecal microbiota in patients with functional constipation undergoing treatment with synbiotics.

Eur J Clin Microbiol Infect Dis 2018 Mar 16;37(3):555-563. Epub 2018 Jan 16.

Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, No. 301 Yanchang Road, Shanghai, 200072, China.

This study was performed to identify changes to microbial composition after treatment with synbiotics in patients with functional constipation and to define the key microbiota in the pathogenesis of functional constipation. Fecal samples from 53 patients diagnosed with chronic functional constipation according to the Rome III criteria were analyzed using 16S rRNA sequencing. After treatment with synbiotics for 1 month, fecal samples were collected from 36 patients; after a total of 3 months, fecal samples were collected from 15 patients. The outcomes were compared with the intestinal microbiota profiles of 53 healthy community volunteers. The microbiota in the constipation group differed from that in the treatment group and healthy group. After synbiotic treatment for 1 and 3 months, the abundance of Escherichia/Shigella decreased, whereas that of Prevotella_9 and Lactococcus increased. Comparison of the microbiota among the three groups showed that Prevotella_9 was the characteristic bacteria that decreased in the constipation group and increased in the treatment group. Synbiotic treatment can improve the microbiota in patients with constipation. Identification of the key bacterial genus is important to reveal the mechanism and provide a reliable theoretical basis of synbiotic treatment. It will also promote relevant research of microbiota treatment and individualized treatments.
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http://dx.doi.org/10.1007/s10096-017-3149-7DOI Listing
March 2018

Identification of molecular mechanisms of glutamine in pancreatic cancer.

Oncol Lett 2017 Dec 26;14(6):6395-6402. Epub 2017 Sep 26.

Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, P.R. China.

The aim of the present study was to explore the critical genes and molecular mechanisms in pancreatic cancer (PC) cells with glutamine. By analyzing microarray data GSE17632 from the Gene Expression Omnibus database, the DEGs between PC cells treated with glutamine and without glutamine were evaluated. Additionally, function enrichment analyses and protein-protein interaction (PPI) network construction of DEGs were performed. Network module and literature mining analyses were performed to analyze the critical DEGs in PC cells. In total, 495 genes were selected as DEGs between control and glutamine cells in PC. These DEGs were mainly enriched in several Gene Ontology (GO) terms in biological process, cellular components and molecular function. Additionally, they were also enriched in certain pathways, including metabolic pathways and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. , heat shock 70kDa protein 5 (), interleukin 8 (), and chemokine (C-X-C motif) receptor 4 () were hub genes in the PPI network. Furthermore, two sub-network modules of PPI network and two co-occurrence networks were obtained. The DEGs of , , and may exert important roles in molecular mechanisms of PC cells with glutamine.
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http://dx.doi.org/10.3892/ol.2017.7068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688798PMC
December 2017

Safety and efficacy of an olive oil-based triple-chamber bag for parenteral nutrition: a prospective, randomized, multi-center clinical trial in China.

Nutr J 2015 Nov 14;14:119. Epub 2015 Nov 14.

Department of Surgery, Shanghai Sixth People's Hospital, Affiliated to Shanghai Jiao Tong University, Shanghai, 200233, China.

Background: Small studies suggest differences in efficacy and safety exist between olive oil-based (OLIVE) and soybean oil-based (SOYBEAN) parenteral nutrition regimens in hospitalized adult patients. This large, prospective, randomized (1:1), open-label, multi-center, noninferiority study compared the delivery, efficacy, and safety of OLIVE (N = 226) with SOYBEAN (N = 232) in Chinese adults (≥18 years) admitted to a surgical service for whom parenteral nutrition was required.

Methods: Treatments were administered for a minimum of 5 days up to 14 days (to achieve approximately 25 kcal/kg/day, 0.9 g/kg/day amino acids, 0.8 g/kg/day lipid). Impact of treatment on anabolic/catabolic and serum inflammatory, chemistry, and hematological markers, safety, and ease of use were assessed. The primary efficacy variable was serum prealbumin level at Day 5.

Results: OLIVE (n = 219) was not inferior to SOYBEAN (n = 224) based on the prealbumin least square geometric mean [LSGM] ratio [95% CI] 1.12 [1.06, 1.19]; P = 0.002), improved the anabolic/catabolic status of patients enrolled in the study, and was well tolerated compared with SOYBEAN. Improved anabolic status was supported by significantly higher levels of prealbumin at Day 5, albumin at Day 5 and IGF-1 at Day 14 in the OLIVE group, while catabolism was similar between groups. C-reactive protein, intercellular adhesion molecule-1, procalcitonin, and oxidation were similar in each group, but infections were significantly lower with OLIVE (3.6% versus 10.4%; P < 0.01).

Conclusions: OLIVE provided effective nutrition, was well tolerated, was associated with fewer infections, and conferred greater ease-of-use than SOYBEAN.

Trial Registration: NTC 01579097.
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http://dx.doi.org/10.1186/s12937-015-0100-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647821PMC
November 2015

Screening of nutritional risk and nutritional support in general surgery patients: a survey from Shanghai, China.

Int Surg 2015 May;100(5):841-8

1 Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

To determine the prevalence of nutritional risk in surgical departments and to evaluate the impact of nutritional support on clinical outcomes. The nutritional risk in different surgical diseases and the different way of nutritional support on clinical outcomes in patients at nutritional risk remain unclear. Hospitalized patients from general surgical departments were screened using the Nutritional Risk Screening (NRS) 2002 questionnaire on admission. Data were collected on nutritional risk, complications, and length of stay (LOS). Overall, 5034 patients were recruited; the overall prevalence of nutritional risk on admission were 19.2%. The highest prevalence was found among patients with gastric cancer. At-risk patients had more complications and longer LOS than nonrisk patients. Of the at-risk patients, the complication rate was significantly lower and LOS was significantly shorter in the nutritional-support group than in the no-support group (20.9 versus 30.0%, P < 0.05). Subgroup analysis showed reduced complication rates and LOS only in patients with gastric cancer, colorectal cancer, and hepato-pancreato-biliary (HPB) cancer. Significantly lower complication rates relative to nonsupported patients were found among patients who received enteral nutrition or who received support for 5 to 7 days, or daily support entailing 16 to 25 kcal/kg of nonprotein energy. Different surgical diseases have different levels of nutritional risk. The provision of nutritional support was associated with a lower complication rate and a shorter LOS for gastric, colorectal, and HPB cancer patients at nutritional risk. The improper use of nutritional support may not improve outcomes for at-risk patients.
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http://dx.doi.org/10.9738/INTSURG-D-14-00245.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452972PMC
May 2015

New endoscopic thyroidectomy with the transareola single-site approach: a comparison with the bilateral areolar approach.

Surg Laparosc Endosc Percutan Tech 2015 Apr;25(2):178-84

Department of General Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai, China.

Purpose: We developed the transareola single-site approach (TASSA) for less invasive endoscopic thyroidectomy to avoid scars on exposed areas. Here, we report our experience with the TASSA technique in treatment of benign thyroid tumors and evaluate its feasibility through comparison with the bilateral areolar approach (BAA).

Methods: From September 2009 to December 2011, 129 patients with benign thyroid tumors were enrolled in the study. Of these patients, 51 patients underwent endoscopic thyroidectomy by TASSA and 78 patients by BAA. The TASSA technique was performed using one 10 mm trocar and one 5 mm trocar through circumareolar incisions using conventional endoscopic instruments. The BAA procedure was performed using one 10 mm trocar and two 5 mm trocars through bilateral circumareolar incisions.

Results: Comparing TASSA with BAA, there were significant differences in the mean operative time (141.96 ± 19.85 vs. 98.14 ± 14.15 min) for lobectomy (P<0.05) and in the subcutaneous dissection area (101.00 ± 6.33 vs. 132.51 ± 5.25 cm, P<0.05). However, there were no significant differences in the duration of hospitalization, amount of drainage, occurrence of postoperative complications, and postoperative pain. All the patients were satisfied with the cosmetic result in the 2 groups.

Conclusions: Endoscopic thyroidectomy using the TASSA procedure is feasible and safe, and affords the advantages of minimal invasiveness and excellent cosmesis results compared with other approaches including BAA. The 2 procedures are technically more challenging procedures, which may become alternative procedures for treatment of patients with benign thyroid tumors, especially those with strong desire for cervical cosmesis.
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http://dx.doi.org/10.1097/SLE.0000000000000119DOI Listing
April 2015

Effect of a high-fat diet in development of colonic adenoma in an animal model.

World J Gastroenterol 2014 Jul;20(25):8119-29

Qing-Chao Zhu, Ren-Yuan Gao, Wen Wu, Bo-Min Guo, Jia-Yuan Peng, Huan-Long Qin, Department of Surgery, the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China.

Aim: To investigate the effect of a high-fat diet in the formation of the precursors of colorectal cancer using an animal model.

Methods: Wistar rats were divided into two groups that were fed either a high-fat diet (HFD) or a normal-fat diet (ND), and 1,2-dimethylhydrazine was administered at a dose of 40 mg/kg for 10 wk. The body weight/liver weight/epididymal fat weight were recorded after rats were sacrificed, and the formation of colonic adenoma was also observed. The levels of insulin, leptin, tumor necrosis factor (TNF)-α, insulin-like growth factor (IGF)-1 and triglycerides were determined by enzyme-linked immunosorbent assay in order to compare the altered levels of biochemical indices and inflammatory cytokines in the serum between rats fed an ND and HFD. Cell proliferation activity (Ki-67) was determined by immunohistochemical analysis. Western blot and immunofluorescence staining were used to examine the expression of proliferating cell nuclear antigen (PCNA), cyclooxygenase (COX)-2, cyclin D1, β-catenin and nuclear factor (NF)-κB proteins in the adenoma and comparative control tissues.

Results: The number of colonic adenomas and the colonic epithelial Ki-67 were significantly higher in the HFD group than in the ND group. The HFD group also had increased body weight, liver weight and epididymal fat weight, which were associated with increased levels of serum insulin, leptin, TNF-α, IGF-1 and triglycerides. HFD induced upregulation of PCNA, COX-2, cyclin D1, β-catenin and NF-κB proteins, as revealed by Western blot and immunofluorescence staining.

Conclusion: HFD promotes the formation of colonic adenoma through inflammation, metabolic abnormalities, and increases cell cycle progression.
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http://dx.doi.org/10.3748/wjg.v20.i25.8119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081683PMC
July 2014

Calcitonin gene-related peptide inhibits osteolytic factors induced by osteoblast in co-culture system with breast cancer.

Cell Biochem Biophys 2014 Nov;70(2):1097-104

Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Recently, it was found that α-Calcitonin gene-related peptide (CGRP) was associated with breast cancer metastases, but the role of CGRP in interaction between breast cancer and osteoblast during bone metastases is not clear. Here, we investigated the effect of CGRP on osteoblast in co-culture system with breast cancer. Using a breast cancer-osteoblast co-culture system, we chose MDA-MB-231 for breast cancer and human cell line MG-63 for osteoblast. CGRP was added to this co-culture system. The expression levels of the Runx2, RANK1, and osteoprotegerin (OPG) were analyzed using real-time PCR and western blot. CGRP receptors were investigated by immunofluorescence. We found that breast cancer cells cause osteolysis lesions by upregulating Runx2 expression, decreasing OPG expression, and increasing RANKL expression in osteoblasts. Our data prove that CGRP can regulate osteoclast coupling genes in osteoblast by increasing OPG, and decreasing RANKL and Runx2 expressions in a time-dependent manner; and inhibit those osteolytic factors induced by interaction between breast cancer cells and osteoblast. This inhibition could be abolished by the CGRP antagonist, CGRP8-37. In conclusion, calcitonin receptor-like receptor is the key player for CGRP's effect in this co-culture system.
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http://dx.doi.org/10.1007/s12013-014-0028-zDOI Listing
November 2014

Combined probiotic bacteria promotes intestinal epithelial barrier function in interleukin-10-gene-deficient mice.

World J Gastroenterol 2014 Apr;20(16):4636-47

Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.

Aim: To investigate the protective effects of combinations of probiotic (Bifico) on interleukin (IL)-10-gene-deficient (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 × 10(8) 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-α and interferon-γ, and attenuated colonic disease. Moreover, treatment of Caco-2 monolayers with Bifico or single-strain 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 epithelial-barrier function, enhanced resistance to EIEC invasion, and decreased proinflammatory cytokine secretion.
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http://dx.doi.org/10.3748/wjg.v20.i16.4636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000500PMC
April 2014

Solitary rectal ulcer syndrome: clinical features, pathophysiology, diagnosis and treatment strategies.

World J Gastroenterol 2014 Jan;20(3):738-44

Qing-Chao Zhu, Yu Wang, Department of Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China.

Solitary rectal ulcer syndrome (SRUS) is an uncommon benign disease, characterized by a combination of symptoms, clinical findings and histological abnormalities. Ulcers are only found in 40% of the patients; 20% of the patients have a solitary ulcer, and the rest of the lesions vary in shape and size, from hyperemic mucosa to broad-based polypoid. Men and women are affected equally, with a small predominance in women. SRUS has also been described in children and in the geriatric population. Clinical features include rectal bleeding, copious mucus discharge, prolonged excessive straining, perineal and abdominal pain, feeling of incomplete defecation, constipation, and rarely, rectal prolapse. This disease has well-described histopathological features such as obliteration of the lamina propria by fibrosis and smooth muscle fibers extending from a thickened muscularis mucosa to the lumen. Diffuse collage deposition in the lamina propria and abnormal smooth muscle fiber extensions are sensitive markers for differentiating SRUS from other conditions. However, the etiology remains obscure, and the condition is frequently associated with pelvic floor disorders. SRUS is difficult to treat, and various treatment strategies have been advocated, ranging from conservative management to a variety of surgical procedures. The aim of the present review is to summarize the clinical features, pathophysiology, diagnostic methods and treatment strategies associated with SRUS.
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http://dx.doi.org/10.3748/wjg.v20.i3.738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921483PMC
January 2014

Epithelial-mesenchymal transition and its role in the pathogenesis of colorectal cancer.

Asian Pac J Cancer Prev 2013 ;14(5):2689-98

Department of Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.

Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogen- activated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-to- mesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.
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http://dx.doi.org/10.7314/apjcp.2013.14.5.2689DOI Listing
January 2015

The effects of perioperative probiotic treatment on serum zonulin concentration and subsequent postoperative infectious complications after colorectal cancer surgery: a double-center and double-blind randomized clinical trial.

Am J Clin Nutr 2013 Jan 12;97(1):117-26. Epub 2012 Dec 12.

Gastrointestinal Institute of Sun Yat-sen University, Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Background: Zonulin is a newly discovered protein that has an important role in the regulation of intestinal permeability. Our previous study showed that probiotics can decrease the rate of infectious complications in patients undergoing colectomy for colorectal cancer.

Objective: The objective was to determine the effects of the perioperative administration of probiotics on serum zonulin concentrations and the subsequent effect on postoperative infectious complications in patients undergoing colorectal surgery.

Design: A total of 150 patients with colorectal carcinoma were randomly assigned to the control group (n = 75), which received placebo, or the probiotics group (n = 75). Both the probiotics and placebo were given orally for 6 d preoperatively and 10 d postoperatively. Outcomes were measured by assessing bacterial translocation, postoperative intestinal permeability, serum zonulin concentrations, duration of postoperative pyrexia, and cumulative duration of antibiotic therapy. The postoperative infection rate, the positive rate of blood microbial DNA, and the incidence of postoperative infectious complications-including septicemia, central line infection, pneumonia, urinary tract infection, and diarrhea-were also assessed.

Results: The infection rate was lower in the probiotics group than in the control group (P < 0.05). Probiotics decreased the serum zonulin concentration (P < 0.001), duration of postoperative pyrexia, duration of antibiotic therapy, and rate of postoperative infectious complications (all P < 0.05). The p38 mitogen-activated protein kinase signaling pathway was inhibited by probiotics.

Conclusions: Perioperative probiotic treatment can reduce the rate of postoperative septicemia and is associated with reduced serum zonulin concentrations in patients undergoing colectomy. We propose a clinical regulatory model that might explain this association. This trial was registered at http://www.chictr.org/en/ as ChiCTR-TRC-00000423.
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http://dx.doi.org/10.3945/ajcn.112.040949DOI Listing
January 2013

Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice.

World J Gastroenterol 2012 Aug;18(30):3977-91

Department of Hepatobiliary Surgery, No. 455 Hospital of People's Liberation Army, Shanghai 200052, China.

Aim: To investigate the mechanisms of Lactobacillus plantarum (L. plantarum) action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats.

Methods: Forty rats were randomly divided into groups of sham-operation, bile duct ligation (BDL), BDL + L. plantarum, BDL + internal biliary drainage (IBD), and BDL + IBD + L. plantarum. Ten days after L. plantarum administration, blood and ileal samples were collected from the rats for morphological examination, and intestinal barrier function, liver function, intestinal oxidative stress and protein kinase C (PKC) activity measurement. The distribution and expression of the PKC and tight junction (TJ) proteins, such as occludin, zonula occludens-1, claudin-1, claudin-4, junction adhesion molecule-A and F-actin, were examined by confocal laser scanning microscopy, immunohistochemistry, Western blotting, real-time fluorescent quantitative polymerase chain reaction assay.

Results: L. plantarum administration substantially restored gut barrier, decreased enterocyte apoptosis, improved intestinal oxidative stress, promoted the activity and expression of protein kinase (BDL vs BDL + L. plantarum, 0.295 ± 0.007 vs 0.349 ± 0.003, P < 0.05; BDL + IBD vs BDL + IBD + L. plantarum, 0.407 ± 0.046 vs 0.465 ± 0.135, P < 0.05), and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice (BDL vs BDL + L. plantarum, 0.266 ± 0.118 vs 0.326 ± 0.009, P < 0.05). The protective effect of L. plantarum was more prominent after internal biliary drainage ( BDL + IBD vs BDL + IBD + L. plantarum, 0.415 ± 0.105 vs 0.494 ± 0.145, P < 0.05).

Conclusion: L. plantarum can decrease intestinal epithelial cell apoptosis, reduce oxidative stress, and prevent TJ disruption in biliary obstruction by activating the PKC pathway.
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http://dx.doi.org/10.3748/wjg.v18.i30.3977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419994PMC
August 2012

SP1 mediates the link between methylation of the tumour suppressor miR-149 and outcome in colorectal cancer.

J Pathol 2013 Jan;229(1):12-24

Department of Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.

Although recent studies indicate that DNA methylation contributes to the down-regulation of microRNAs (miRNAs) in colorectal cancer (CRC), this field remains largely unexplored. To identify methylation-silenced miRNAs and clarify their role in CRC, we performed a microarray analysis and screened for miRNAs that were induced in CRC cells by 5-aza-2'-deoxycytidine treatment or by the knockdown of DNA methyltransferases. The DNA methylation status of the candidate miRNA was analysed by bisulphite sequencing PCR and methylation-specific PCR. We found that miRNA-149 (miR-149) was epigenetically silenced in CRC and down-regulation of miR-149 was associated with hypermethylation of the neighbouring CpG island (CGI). Quantitative RT-PCR analysis demonstrated that the miR-149 level was markedly reduced in 51.6% of the CRC tissues compared with matched non-cancerous tissues. In addition, low expression of miR-149 was associated with a greater depth of invasion (p = 0.012), lower 5-year survival rate (p = 0.025), and was found to be an independent prognostic factor for overall survival (p = 0.016) in a multivariate analysis. Moreover, transfection of miR-149 inhibited cell growth and invasion of CRC cells in vitro. We also identified mRNA for Specificity Protein 1 (SP1, Sp1), a potential oncogenic protein, as a target of miR-149. Our data suggest that, as a methylation-sensitive miRNA, miR-149 may play an important role as a tumour suppressor in CRC, which has prognostic and therapeutic implications.
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http://dx.doi.org/10.1002/path.4078DOI Listing
January 2013

UHRF1 promotes cell growth and metastasis through repression of p16(ink⁴a) in colorectal cancer.

Ann Surg Oncol 2012 Aug 5;19(8):2753-62. Epub 2012 Jan 5.

Department of Surgery, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.

Purpose: To investigate whether ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) expression is upregulated in colorectal cancer (CRC), whether UHRF1 promotes CRC cell growth and migration and the underlying molecular mechanism.

Methods: UHRF1 protein expression was determined in 144 pairs of primary CRC and their corresponding adjacent nontumor tissues by immunohistochemistry with tissue microarrays. UHRF1 mRNA expression was assessed in 20 pairs of the above tissues and four colon cancer cell lines by quantitative reverse transcriptase-polymerase chain reaction. Associations of UHRF1 expression with demographic and clinicopathologic features were determined. Additionally, the effects of lentiviral-mediated RNA interference (RNAi) of UHRF1 on cell proliferation and migration, cell cycle and apoptosis, and the expression of p16(ink4a) and p21(waf1/cip1) were investigated in CRC cell lines.

Results: UHRF1 was overexpressed in CRC tissues and cell lines. UHRF1 protein expression levels correlated with the presence of lymph nodes (P = 0.005), distal metastasis (P = 0.030), poor Dukes staging (P = 0.001), and absence of p16(ink4a) expression (P = 0.002). RNAi of UHRF1 inhibited proliferation and migration, and induced apoptosis and cell cycle arrest at the G0/G1 phase. Furthermore, RNAi of UHRF1 enhanced the expression of p16(ink4a), but not p21(waf1/cip1), in CRC cells.

Conclusions: UHRF1 expression is upregulated in CRC and is associated with the progression of CRC. Moreover, RNAi of UHRF1 decreases proliferation and migration but enhances apoptosis of CRC cells, with increased p16(ink4a) expression. UHRF1 promotes CRC growth and metastasis, likely by repressing p16(ink4a), and thus it may be used as a biomarker or even a therapeutic target for CRC.
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http://dx.doi.org/10.1245/s10434-011-2194-1DOI Listing
August 2012

Histidine decarboxylase is identified as a potential biomarker of intestinal mucosal injury in patients with acute intestinal obstruction.

Mol Med 2011 9;17(11-12):1323-37. Epub 2011 Sep 9.

Department of Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.

Various biomarkers currently used for the diagnosis of intestinal mucosal injury (IMI) in patients with acute intestinal obstruction have low sensitivity and specificity. In the present study, IMI, as indicated by the impaired expression of tight junction proteins, including zonula occludens-1, occludin and claudin-1, and inflammation were determined in colonic tissues of patients with 45 strangulated intestinal obstruction (STR-IO) and the adjacent "normal" colonic tissues of 35 patients with colon cancers by quantitative real-time polymerase chain reaction (QRT-PCR), Western blotting, immunohistochemistry and histological examination, respectively. Then, two-dimensional fluorescent difference gel electrophoresis coupled with linear trap quadrupole mass spectrometry was used to screen for potential biomarkers of IMI in the serum samples of 10 STR-IO, 10 simple intestinal obstruction (SIM-IO) and 10 normal healthy controls. A total of 35 protein spots were differentially expressed among the serum samples, and six of the proteins were identified as potential biomarkers. Among the six proteins, histidine decarboxylase (HDC) and ceruloplasmin (CP) were elevated significantly in patients with STR-IO, compared with patients with SIM-IO and healthy controls. Thus, HDC and CP were further validated by QRT-PCR, Western blotting, immunohistochemistry and enzyme-linked immunosorbent assay, respectively, in colonic tissues, serum and urine samples. Finally, the receiver operating characteristic curves were used to show the area under the curves of HDC, CP and several established biomarkers, followed by the determination of the appropriate cutoff values and their sensitivities and specificities. It was shown that for serum and urine, HDC levels achieved sensitivities and specificities compatible to or even greater than those of established biomarkers for the diagnosis of IMI in patients with acute intestinal obstruction, although further validation in a larger cohort is required.
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http://dx.doi.org/10.2119/molmed.2011.00107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321802PMC
August 2012

A genetic variant in microRNA-196a2 is associated with increased cancer risk: a meta-analysis.

Mol Biol Rep 2012 Jan 31;39(1):269-75. Epub 2011 May 31.

Department of Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, 600 Yishan Road, Shanghai, 200233, People's Republic of China.

MicroRNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. Common genetic variants (single nucleotide polymorphisms, SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences. Until now, several studies had evaluated the association between the polymorphisms in the hsa-miR-196a2 rs11614913 and cancer risk in diverse populations and in multiple types of cancer, with contradictory outcomes. Therefore, here we performed a meta-analysis to address the association between this polymorphism and cancer risk. A total of nine studies involving 6,540 cases and 7,562 controls were retrieved based on PubMed. Our analysis demonstrated that hsa-miR-196a2 rs11614913 CC genotype significantly increased the cancer risk in homozygote comparison model compared to TT genotype (OR=1.18; 95% CI, 1.01-1.68). Moreover, significant association of this polymorphism with breast cancer was found based on homozygote comparison model (OR=1.30; 95% CI, 1.01-1.26) and dominant model (OR=1.11; 95% CI, 1.01-1.23). In addition, hsa-miR-196a2 rs11614913 CC genotype was significantly associated with cancer risk in Chinese and Indian (OR=1.21; 95% CI, 1.05-1.40), but not in Caucasians (OR=1.03; 95% CI, 0.89-1.19). Taken together, our results indicate that the polymorphism of hsa-miR-196a2 rs11614913 is associated with cancer susceptibility, especially with breast cancer and in Chinese and Indian populations.
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http://dx.doi.org/10.1007/s11033-011-0735-0DOI Listing
January 2012

[Effect of enteral nutrition on liver function and inflammatory response after abdominal operation in patients complicated with liver dysfunction].

Zhonghua Wei Chang Wai Ke Za Zhi 2011 May;14(5):336-9

Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.

Objective: To investigate the effect of enteral nutrition(EN) on liver function and inflammatory response after abdominal operation in patients with liver dysfunction.

Methods: A prospective multicenter study was conducted. Patients requiring EN for at least 5 days after abdominal surgery with at least 1 abnormal liver function index were included. After operations, EN suspensions(TPF-FOS) were administered for 5 days after the return of bowel function with targeted content of 125.52 kJ(30 kcal)·kg(-1)·d(-1) maintained for a minimum of 3 days. Levels of serum pre-albumin, C-reaction protein(CRP), and liver function index were measured and the incidence of systemic inflammatory response syndrome(SIRS) was recorded before operation and 6 days after EN. Occurrence of gastrointestinal discomfort was monitored during the treatment.

Results: No statistically significant difference was found in pre-albumin between preoperative level and post-EN level[(175.94±71.79) mg/L vs.(192.22±91.26) mg/L, P=0.162]. Patients with abnormal level of γ-glutamyl transpeptidase were less after EN compared to the preoperative period(30 vs. 40, P=0.041), as was total bilirubin (3 vs. 9, P=0.034). No significant differences in other indices of liver function were found. Total bilirubin and direct bilirubin decreased after EN support(P=0.000 and P=0.015, respectively). CRP was notably reduced after EN support [(48.74±65.16) mg/L vs.(25.79±23.63) mg/L, P=0.009] and the incidence of SIRS largely declined after EN support(19.0% vs. 10.3%, P=0.059). The incidence of gastrointestinal discomfort was 22.4% on postoperative day 1 and declined to 19.0% on postoperative day 5.

Conclusion: For patients with liver dysfunction, enteral nutrition support with TPF-FOS after abdominal operation can reduce inflammatory response, improve liver function, and maintain serum protein level.
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May 2011

Effect of Lactobacillus plantarum LP-Onlly on gut flora and colitis in interleukin-10 knockout mice.

J Gastroenterol Hepatol 2011 Feb;26(2):405-11

Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.

Background And Aim: Probiotics are used in the therapy of inflammatory bowel disease. This study aimed to determine the effects of probiotic Lactobacillus plantarum LP-Onlly (LP) on gut flora and colitis in interleukin-10 knockout (IL-10(-/-) ) mice, a model of spontaneous colitis.

Methods: IL-10(-/-) and wild-type mice were used at 8 weeks of age and LP by gavage was administered at a dose of 10(9) cells/day per mice for 4 weeks. Mice were maintained for another one week without LP treatment. The colonic tissues were collected for histological and ultrastructural analysis at death after 4 weeks treatment of LP, and the feces were collected at 1-week intervals throughout the experiment for the analysis of gut flora and LP using selective culture-based techniques.

Results: Compared with control mice, IL-10(-/-) mice developed a severe intestinal inflammation and tissue damage, and had an abnormal composition of gut microflora. LP administration attenuated colitis with the decreased inflammatory scoring and histological injury in the colon of IL-10(-/-) mice. In addition, LP administration increased the numbers of beneficial total bifidobacteria and lactobacilli, and decreased the numbers of potential pathogenic enterococci and Clostridium perfringens, although the decrease of coliforms was not significant after LP treatment in IL-10(-/-) mice.

Conclusions: Oral administration of LP was effective in the treatment of colitis, with the direct modification of gut microflora in IL-10(-/-) mice. This probiotic strain could be used as a potential adjuvant in the therapy of inflammatory bowel disease, although further studies are required in human.
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http://dx.doi.org/10.1111/j.1440-1746.2010.06498.xDOI Listing
February 2011

Protective effects of Lactobacillus plantarum against epithelial barrier dysfunction of human colon cell line NCM460.

World J Gastroenterol 2010 Dec;16(45):5759-65

Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.

Aim: To investigate the effects of Lactobacillus plantarum (L. plantarum) in the intestinal permeability and expression of tight junction (TJ) using the normal human colon cell line NCM460.

Methods: Paracellular permeability of NCM460 monolayers was determined by transepithelial electrical resistance and dextran permeability. Expression of TJ proteins in NCM460 cell monolayers was detected by Western blotting and quantitative real-time polymerase chain reaction.

Results: L. plantarum played an important role in increasing transepithelial electrical resistance and decreasing the permeability to macromolecules of NCM460 monolayers against the disruption caused by enteropathogenic Escherichia coli (E. coli) or enteroinvasive E. coli. L. plantarum also prevented the decrease in the expression of TJ proteins and F-actin in NCM460 cells.

Conclusion: L. plantarum can protect against dysfunction of NCM460 intestinal epithelial barrier caused by enteropathogenic E. coli or enteroinvasive E. coli, and thus can be a potential candidate of therapeutic agents for the treatment of intestinal diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997994PMC
http://dx.doi.org/10.3748/wjg.v16.i45.5759DOI Listing
December 2010

Percutaneous injection of chemotherapeutic drugs in the guidance of magnetic resonance imaging for the treatment of cholangiocarcinoma.

Med Sci Monit 2010 Dec;16(12):HY31-3

Department of Surgery, Shanghai Jiao Tong University, Affiliated Sixth People's Hospital, Shanghai, China.

The morbidity and mortality of cholangiocarcinoma have been rising yearly. However, conventional therapies still cannot achieve a satisfactory survival rate. Furthermore, there is an urgent need to discover new approaches to overcome chemotherapeutic drug resistance of cholangiocarcinoma. Considering the unique advantage of magnetic irradiation, we hypothesize that percutaneous injection of chemotherapeutic drugs in the guidance of nuclear magnetic resonance imaging may enhance the survival rate of cholangiocarcinoma without increasing undesired side effects.
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December 2010

Lactobacillus plantarum consumption increases PepT1-mediated amino acid absorption by enhancing protein kinase C activity in spontaneously colitic mice.

J Nutr 2010 Dec 27;140(12):2201-6. Epub 2010 Oct 27.

Department of General Surgery, Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.

Although probiotic consumption has generally been shown to have many beneficial effects for the prevention and treatment of inflammatory bowel disease, the effects of Lactobacillus plantarum (LP) on intestinal nutrient absorption, particularly oligopeptide transporter 1 (PepT1)-mediated absorption of dietary protein under inflammatory conditions, has not yet been characterized. In this study, we first investigated the effects of LP consumption on plasma amino acid concentrations and PepT1-mediated absorption of cephalexin in the small intestine of wild-type (WT) mice and interleukin-10 knockout (IL-10(-/-)) mice, a model of spontaneous colitis. We then analyzed expression and distribution of PepT1 and protein kinase C (PKC) activity in the jejunum of these mice. LP consumption (10(9) colony-forming units/0.5 mL) delivered by gavage once per day for 4 wk increased the total plasma amino acid concentration and the concentration of plasma cephalexin through enhancement of PepT1-mediated uptake in LP treated IL-10(-/-) mice compared with IL-10(-/-) mice. However, Western blotting and quantitative PCR analysis revealed no significant differences in PepT1 protein and mRNA expression between LP-treated and untreated mice. Additionally, immunofluorescence analysis showed that PepT1 did not appear to be mislocalized in IL-10(-/-) mice. Interestingly, IL-10(-/-) mice had significantly lower PKC activity and expression of phosphorylated PKC compared with WT mice, and these decreases could be prevented by LP treatment. These data suggest that consumption of LP enhances PepT1-mediated amino acid absorption, likely through alterations in PKC activity, as opposed to changes in expression or distribution of PepT1 in the small intestine of IL-10(-/-) mice.
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http://dx.doi.org/10.3945/jn.110.123265DOI Listing
December 2010

Lactobacillus plantarum ameliorates colonic epithelial barrier dysfunction by modulating the apical junctional complex and PepT1 in IL-10 knockout mice.

Am J Physiol Gastrointest Liver Physiol 2010 Dec 30;299(6):G1287-97. Epub 2010 Sep 30.

Dept. of General Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong Univ., People's Republic of China.

Probiotics are efficacious in the treatment of inflammatory bowel disease. However, the precise mechanisms remain unknown. To determine whether probiotic Lactobacillus plantarum (LP) ameliorates colonic epithelial barrier dysfunction present in interleukin-10 knockout (IL-10⁻(/)⁻) mice, IL-10⁻(/)⁻ and wild-type mice received LP or the vehicle for 4 wk. Colitis was assessed by histological scores and clinical manifestation, and gut paracellular permeability was measured by Ussing chamber. Oligopeptide transporter 1 (PepT1)-mediated transepithelial transport was evaluated by measuring the plasma cephalexin concentration. The expression and distribution of apical junctional complex (AJC) proteins and PepT1 were determined by Western blotting and immunofluorescence and their mRNA by reverse transcriptase-PCR. Spontaneous colitis was observed in all IL-10⁻(/)⁻ mice in which paracellular permeability was increased, in conjunction with decreased expression and redistribution of zonula occludens-1, occludin, claudin-1, and β-catenin. PepT1 expression was increased, accompanied with an enhanced cephalexin transport. Colonic epithelial barrier dysfunction was further confirmed by increased bacterial translocation and proinflammatory cytokine production. Treatment with LP decreased colonic paracellular permeability with restoration of expression and distribution of AJC proteins and partially prevented PepT1 expression and cephalexin transport in IL-10⁻(/)⁻ mice. Moreover, treatment with LP also prevented bacterial translocation and proinflammatory cytokine production in IL-10⁻(/)⁻ mice. Results from this study indicated that treatment with LP may ameliorate colonic epithelial barrier dysfunction in IL-10⁻(/)⁻ mice, by modulating the AJC- and PepT1-mediated transepithelial transport.
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http://dx.doi.org/10.1152/ajpgi.00196.2010DOI Listing
December 2010

Human embryonic stem cells and metastatic colorectal cancer cells shared the common endogenous human microRNA-26b.

J Cell Mol Med 2011 Sep;15(9):1941-54

Department of Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China.

The increase in proliferation and the lack of differentiation of cancer cells resemble what occur in the embryonic stem cells during physiological process of embryogenesis. There are also striking similarities in the behaviour between the invasive placental cells and invasive cancer cells. In the present study, microarrays were used to analyse the global expression of microRNAs in a human embryonic stem cell line (i.e. HUES-17) and four colorectal cancer (CRC) cell lines (i.e. LoVo, SW480, HT29 and Caco-2) with different metastatic potentialities. Only the expression of miR-26b was significant decreased in HUES-17s and LoVo cells, compared with other three cell lines (P < 0.01). The quantitative real-time PCR analysis confirmed the results of the microarray analysis. Overexpression of miR-26b expression by miR-26 mimics transfection and led to the significant suppression of the cell growth and the induction of apoptosis in LoVo cells in vitro, and the inhibition of tumour growth in vivo. Moreover, the potential targets of miR-26b was predicted by using bioinformatics, and then the predicted target genes were further validated by comparing gene expression profiles between LoVo and NCM460 cell lines. Four genes (TAF12, PTP4A1, CHFR and ALS2CR2) with intersection were found to be the targets of miR-26b. MetaCore network analysis further showed that the regulatory pathways of miR-26b were significantly associated with the invasiveness and metastasis of CRC cells. These data suggest that miR-26b might serve as a novel prognostic factor and a potential therapeutic target for CRC.
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http://dx.doi.org/10.1111/j.1582-4934.2010.01170.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918049PMC
September 2011

[Effect of bowel preparation with probiotics on intestinal barrier after surgery for colorectal cancer].

Zhonghua Wei Chang Wai Ke Za Zhi 2010 Jul;13(7):528-31

Department of Surgery, The 6th People Hospital of Shanghai, Shanghai Jiaotong University, Shanghai 200233, China.

Objective: To study the effect of bowel preparation with probiotics on intestinal barrier function after surgery for colorectal cancer.

Methods: A total of 60 patients undergone colonic surgery were randomly divided into two groups:the trial group and the control group. One-day bowel preparation with probiotics was administered in trial group, while 3-day conventional bowel preparation in control group. Quality of the preparation was estimated during operation and the structure of intestinal epithelium in the colon was observed by microscope. Levels of transmembrane binding protein(occludin) and IgA in the colon were detected by immunohistochemistry method. White blood cell counts, microbial DNA, and C-reactive protein were measured before surgery and 1, 7 days after surgery. Postoperative systemic inflammation response syndrome(SIRS) and infection were evaluated.

Results: Good and excellent bowel preparation were achieved in 88% in the trial group and 92% in the control group(P=0.072). The expression levels of occludin and IgA of colon were significantly higher in the trial group[(19.32 + or - 2.40)% and (7.60 + or - 1.48)%, respectively] compared with those of the control group [(16.21 + or - 2.54)% and (5.29 + or - 1.57)%,respectively]. The number of microbial DNA PCR-positive patients in the trial group was significantly less than that in the control group after operation. There were no significant differences in the rates of SIRS or complications between the two groups.

Conclusion: One-day bowel preparation with probiotics can maintain the intestinal barrier function after surgery of colorectal cancer,which is suitable for elective colorectal surgery.
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July 2010

Gemcitabine combined with gum mastic causes potent growth inhibition and apoptosis of pancreatic cancer cells.

Acta Pharmacol Sin 2010 Jun;31(6):741-5

Department of Surgery, the Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.

Aim: To investigate the antiproliferative and apoptotic effects of gemcitabine combined with gum mastic and the underlying mechanisms in human pancreatic cancer cell lines.

Methods: Cell proliferation and apoptosis were examined using the methyl thiazolyl tetrazolium (MTT) assay and propidium iodine staining, respectively. The expression of Bcl-2, Bax, NF-kappaB p65 subunit, and IkappaBalpha protein was measured using Western blotting.

Results: Gemcitabine 0.01-100 microg/mL inhibited cell proliferation and induced apoptosis in both pancreatic cancer BxPC-3 and COLO 357 cells. Gum mastic 40 microg/mL significantly potentiated the antiproliferative and apoptotic effects of gemcitabine 10 microg/mL after 72-h treatment. When cells were treated with gemcitabine in combination with gum mastic, the IkappaBalpha level was increased, whereas NF-kappaB activation was blocked; the expression of Bax protein was substantially increased, but Bcl-2 protein was down-regulated.

Conclusion: Gemcitabine combined with gum mastic causes potent apoptosis in pancreatic cancer cells. The combination may be an effective therapeutic strategy for pancreatic cancer.
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http://dx.doi.org/10.1038/aps.2010.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002976PMC
June 2010

HnRNP K and PDI marked response to chemotherapy to human colorectal cancer cells.

Electrophoresis 2010 May;31(10):1731-8

Department of Surgery, Sixth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai, PR China.

Unlabelled: 5-Fluorouracil has been the chemotherapy agent of first-choice for colorectal cancer for many years, but since there are no proven predictors of a patient's response to therapy, all patients receive similar treatment. Consequently, identification of biomarkers for therapeutic effect is crucial for the development of novel therapeutic strategies. Two human colorectal cancer cell lines of different metastatic potential (LoVo and SW480) were studied. IC50 of 5-FU for both cell lines were measured by 3-(4,5-dimethy-lthiazol-2-yl)-2,5-diphenyltetrazolium assay and validated by cell cycle analysis. Then the cell lines were treated with 5-FU at IC50 concentration and protein was extracted for 2-DE. Differential protein spots were examined by MALDI-TOF/TOF MS. The expression levels of the different proteins were further confirmed by Western blot and immunofluorescence analyses. Eleven proteins were identified. Expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K) in LoVo cells was higher than in SW480 cells, while protein disulfide isomerase (PDI) displayed the opposite trend. After treatment with 5-FU, the expression of hnRNP K in LoVo decreased more significantly than in SW480, while PDI in SW480 increased more significantly than in LoVo cells.

Conclusion: hnRNP K and PDI in the two cell lines have different expression characteristics. The sensitivity to 5-FU is not consistent in tumor progression. It may assist in development of novel treatment strategies for colorectal cancer metastasis.
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http://dx.doi.org/10.1002/elps.200900495DOI Listing
May 2010
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