Glycerol monolaurate ameliorates DSS-induced acute colitis by inhibiting infiltration of Th17, neutrophils, macrophages and altering the gut microbiota.

Background and aims: Inflammatory bowel disease (IBD) places a heavy medical burden on countries and families due to repeated and prolonged attacks, and the incidence and prevalence of IBD are increasing worldwide. Therefore, finding an effective treatment is a matter of great urgency. Glycerol monolaurate (GML), which has a twelve-carbon chain, is a compound naturally found in human breast milk. Some studies have shown that GML has antibacterial and anti-inflammatory effects. However, the specific mechanism of action remains unclear. Methods: Acute colitis was established in mice using 3% DSS, and glycerol monolaurate (500 mg·kg-1) was administered for two weeks. QPCR and western blotting were performed to examine the inflammatory status. Mice described were subjected to flow cytometry analysis for immune cell activation. Results: GML treated alleviated macroscopic symptoms such as shortened colons, increased spleen weight, and caused weight loss in mice with DSS-induced colitis. In addition, GML decreased the expression of pro-inflammatory factors (NF-α, IL-1ß and IL-1α) and increased the expression of anti-inflammatory factors (IL-10 and TGF-ß). GML inhibited the activation of the MAPK and NF-κB signalling pathways, improved tissue damage, and increased the expression of intestinal tight junction proteins. In addition, LPMCs extracted from intestinal tissue via flow cytometry showed that GML treatment led to a decrease of Th17 cells, Neutrophils and Macrophages. 16S rDNA sequencing showed that GML increased the abundance of commensal bacterium such as Akkermansia and Lactobacillus murinus. Conclusions: We showed that oral administration of GML ameliorated DSS-induced colitis by inhibiting infiltration of Th17 cells, Neutrophils, and Macrophages, protecting the intestinal mucosal barrier and altered the abundance of commensal bacterium. This study provides new insights into the biological function and therapeutic potential of GML in the treatment of IBD.

Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.

BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).

Mindin serves as a tumour suppressor gene during colon cancer progression through MAPK/ERK signalling pathway in mice.

Mindin is important in broad spectrum of immune responses. On the other hand, we previously reported that mindin attenuated human colon cancer development by blocking angiogenesis through Egr-1-mediated regulation. However, the mice original mindin directly suppressed the syngenic colorectal cancer (CRC) growth in our recent study and we aimed to further define the role of mindin during CRC development in mice. We established the mouse syngeneic CRC CMT93 and CT26 WT cell lines with stable mindin knock-down or overexpression. These cells were also subcutaneously injected into C57BL/6 and BALB/c mice as well as established a colitis-associated colorectal cancer (CAC) mouse model treated with lentiviral-based overexpression and knocked-down of mindin. Furthermore, we generated mindin knockout mice using a CRISPR-Cas9 system with CAC model. Our data showed that overexpression of mindin suppressed cell proliferation in both of CMT93 and CT26 WT colon cancer cell lines, while the silencing of mindin promoted in vitro cell proliferation via the ERK and c-Fos pathways and cell cycle control. Moreover, the overexpression of mindin significantly suppressed in vivo tumour growth in both the subcutaneous transplantation and the AOM/DSS-induced CAC models. Consistently, the silencing of mindin reversed these in vivo observations. Expectedly, the tumour growth was promoted in the CAC model on mindin-deficient mice. Thus, mindin plays a direct tumour suppressive function during colon cancer progression and suggesting that mindin might be exploited as a therapeutic target for CRC.

Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study.

BACKGROUND: Chemoprevention of colorectal adenoma and colorectal cancer remains an important public health goal. The present study aimed to investigate the clinical potential and safety of berberine for prevention of colorectal adenoma recurrence. METHODS: This double-blind, randomised, placebo-controlled trial was done in seven hospital centres across six provinces in China. Individuals aged 18-75 years who had at least one but no more than six histologically confirmed colorectal adenomas that had undergone complete polypectomy within the 6 months before recruitment were recruited and randomly assigned (1:1) to receive berberine (0·3 g twice daily) or placebo tablets via block randomisation (block size of six). Participants were to undergo a first follow-up colonoscopy 1 year after enrolment, and if no colorectal adenomas were detected, a second follow-up colonoscopy at 2 years was planned. The study continued until the last enrolled participant reached the 2-year follow-up point. All participants, investigators, endoscopists, and pathologists were blinded to treatment assignment. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. Analysis was based on modified intention-to-treat, with the full analysis set including all randomised participants who received at least one dose of study medication and who had available efficacy data. The study is registered with ClinicalTrials.gov, number NCT02226185; the trial has ended and this report represents the final analysis. FINDINGS: Between Nov 14, 2014, and Dec 30, 2016, 553 participants were randomly assigned to the berberine group and 555 to the placebo group. The full analysis set consisted of 429 participants in the berberine group and 462 in the placebo group. 155 (36%) participants in the berberine group and 216 (47%) in the placebo group were found to have recurrent adenoma during follow-up (unadjusted relative risk ratio for recurrence 0·77, 95% CI 0·66-0·91; p=0·001). No colorectal cancers were detected during follow-up. The most common adverse event was constipation (six [1%] of 446 patients in the berberine group vs one [<0·5%] of 478 in the placebo group). No serious adverse events were reported. INTERPRETATION: Berberine 0·3 g twice daily was safe and effective in reducing the risk of recurrence of colorectal adenoma and could be an option for chemoprevention after polypectomy. FUNDING: National Natural Science Foundation of China.

The pattern-recognition molecule mindin binds integrin Mac-1 to promote macrophage phagocytosis via Syk activation and NF-κB p65 translocation.

Mindin has a broad spectrum of roles in the innate immune system, including in macrophage migration, antigen phagocytosis and cytokine production. Mindin functions as a pattern-recognition molecule for microbial pathogens. However, the underlying mechanisms of mindin-mediated phagocytosis and its exact membrane receptors are not well established. Herein, we generated mindin-deficient mice using the CRISPR-Cas9 system and show that peritoneal macrophages from mindin-deficient mice were severely defective in their ability to phagocytize E  coli. Phagocytosis was enhanced when E  coli or fluorescent particles were pre-incubated with mindin, indicating that mindin binds directly to bacteria or non-pathogen particles and promotes phagocytosis. We defined that 131 I-labelled mindin binds with integrin Mac-1 (CD11b/CD18), the F-spondin (FS)-fragment of mindin binds with the αM -I domain of Mac-1 and that mindin serves as a novel ligand of Mac-1. Blockade of the αM -I domain of Mac-1 using either a neutralizing antibody or si-Mac-1 efficiently blocked mindin-induced phagocytosis. Furthermore, mindin activated the Syk and MAPK signalling pathways and promoted NF-κB entry into the nucleus. Our data indicate that mindin binds with the integrin Mac-1 to promote macrophage phagocytosis through Syk activation and NF-κB p65 translocation, suggesting that the mindin/Mac-1 axis plays a critical role during innate immune responses.

A single factor induces neuronal differentiation to suppress glioma cell growth.

AIM: Glioma, with fast growth and progression features, is the most common and aggressive tumor in the central nervous system and is essentially incurable. This study is aimed at inducing neuronal differentiation to suppress glioma cell growth with a single transcription factor. METHODS: Overexpression of transcription factor SRY (sex determining region Y)-box 11 (SOX11) and Zic family member 1 (ZIC1) was, respectively, performed in glioma cells with lentivirus infection. CRISPR/Cas9 technology was used to knock out ZIC1 in U87 cells, and knockout efficiency was identified by Western blotting and Sanger sequencing. Cell cycle and apoptosis were detected by flow cytometry. The downstream targets of SOX11 were analyzed by Affymetrix GeneChip microarrays. qRT-PCR and immunofluorescence technique were used to verify gene targets of genetically modified U87 cells. All the cells were imaged by a fluorescence microscope. Gene expression correlation analysis and overall survival analysis based on TCGA dataset are performed by GEPIA. RESULTS: We induced glioma cells into neuron-like cells to suppress cell growth using a single transcription factor, SOX11 or ZIC1. Besides, we proved that there is a strong correlation between SOX11 and ZIC1. Our study revealed that SOX11 upregulates ZIC1 expression by binding with ZIC1 promoter, and ZIC1 partially mediates SOX11-induced neuronal differentiation in U87 cells. However, SOX11 expression is not regulated by ZIC1. Moreover, high MAP2 expression means better overall survival in TCGA lower grade glioma. CONCLUSION: This study revealed that glioma cells can be reprogrammed into neuron-like cells using a single factor ZIC1, which may be a potential tumor suppressor gene for gliomas treatment.

Peptic Ulcer Is the Most Common Cause of Non-Variceal Upper-Gastrointestinal Bleeding (NVUGIB) in China.

BACKGROUND This study aimed to discover the common cause of non-variceal upper-gastrointestinal bleeding (NVUGIB) by conducting a multi-center retrospective study from 2008 to 2012. MATERIAL AND METHODS Hospitalized patients ages ≥18 years old, from 8 hospitals in China, diagnosed with NVUGIB by endoscopy from 1 January 2008 to 31 December 2012 were enrolled. Questionnaires were developed and a data-entry graphical user interface was designed by using EpiData software. RESULTS Total of 2977 hospitalized patients from 8 medical centers were included. A total of 95.47% (2842/2977) of patients were admitted to a general ward, 3.53% (105/2977) were admitted to an emergency ward, and 1.00% (31/2977) were admitted to an intensive care unit. Peptic ulcer remained the most common cause of NVUGIB (73.26%), but there was a declining trend in its constituent ratio, from 2008 to 2012. A total of 14.41% (429/2977) of patients had co-morbid conditions, 92.85% (2764/2977) used proton-pump inhibitors (PPIs) prior to endoscopic treatment, 19.65% (585/2977) underwent emergency endoscopy, and 23.45% (698/2977) received a transfusion of red blood cell suspensions. A total of 5.34% (159/2977) underwent endoscopic therapy, with a treatment rate of 16.9% in high-risk peptic ulcer patients (96/568). A total of 7.69% (237/2977) were administered aspirin, of whom 32.50% (77/237) resumed aspirin intake after gastrointestinal bleeding was controlled. The median length of hospitalization was 8 days (IQR, 5-11) and the mortality rate was 1.71% (51/2977). CONCLUSIONS Peptic ulcer was still the most common cause of NVUGIB in China. The proportion of patients with high-risk peptic ulcer bleeding who received endoscopic therapy was 16.9%. Only 19.65% of NVUGIB patients underwent emergency endoscopy.

Polaprezinc combined with clarithromycin-based triple therapy for Helicobacter pylori-associated gastritis: A prospective, multicenter, randomized clinical trial.

The efficacy and safety of polaprezinc combined with triple therapy was compared with triple therapy alone in the eradication of Helicobacter pylori. A randomized, parallel-group, open-label, controlled, prospective multicenter study was conducted in 11 cities in China. Treatment-naive patients with H. pylori-associated gastritis were randomly assigned to one of three arms for a 14-day treatment: Arm A triple therapy (omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, each twice daily) plus polaprezinc 75 mg twice daily; Arm B triple therapy plus polaprezinc 150 mg twice daily, or Arm C triple therapy alone. The rate of H. pylori eradication was the primary endpoint. Secondary endpoints were symptom improvement and lower incidence of adverse events. 303 patients completed the study- 106, 96, and 101 patients in Arms A, B, and C, respectively. Intention-to-treat (ITT) analysis showed that the rate of H. pylori eradication was significantly higher for Arms A (77.0%) and B (75.9%) compared to Arm C (58.6%) (P < 0.01), whereas there was no difference between Arms A and B (P = 0.90). Per-protocol (PP) analysis showed that the rate of H. pylori eradication was significantly higher for Arms A (81.1%) and B (83.3%) compared to Arm C (61.4%) (P < 0.01), whereas there was no significant difference between Arms A and B (P = 0.62). All three groups reported significant symptom improvement at 7, 14, and 28 days after treatment, compared to baseline (P < 0.0001). The adverse event rate for Arm B (5.1%) was higher than for Arms A (2.8%) (P = 0.04) and C (1.9%) (P = 0.02). There were no serious adverse events in any group. It appears that standard dose polaprezinc combined with triple therapy can significantly improve the H. pylori eradication rate, without an increase in toxicity.

A network pharmacology approach to establish the pharmacological mechanism of JiaWeiXianJiTang on inflammatory bowel disease.

The aim of the present study was to characterize the molecular mechanism of the effective components of JiaWeiXianJiTang (JWXJT), a traditional Chinese medicine, on inflammatory bowel disease (IBD) using network pharmacology technology. Data regarding natural molecules of JWXJT, targets of IBD, and interactions between natural molecules and IBD targets were screened. Network pharmacology of the interactions between natural molecules and IBD targets were drawn using Cytoscape v3.2.1. As a result of screening, 205 interactions were identified between 673 natural molecules and 76 targets of IBD. By analyzing the effective components, the complex effect mechanism of JWXJT on IBD was identified to be via enhancement of the immune system, inhibiting novel blood vessel growth through 15-hydroxyprostaglandin dehydrogenase, 5' AMP-activated protein kinase, interleukin-2 and macrophage colony-stimulating factor-1, and resulting in inflammation inhibition. In addition, JWXJT ameliorated IBD by antagonizing various molecular targets of IBD through its effective components, inhibiting inflammatory reactions, improving patient quality of life, as well as reducing the incidence of cancer.

Therapeutic targeting of liver cancer with a recombinant DNA vaccine containing the hemagglutinin-neuraminidase gene of Newcastle disease virus via apoptotic-dependent pathways.

A total of ~38.6 million mortalities occur due to liver cancer annually, worldwide. Although a variety of therapeutic methods are available, the efficacy of treatment at present is extremely limited due to an increased risk of malignancy and inherently poor prognosis of liver cancer. Gene therapy is considered a promising option, and has shown notable potential for the comprehensive therapy of liver cancer, in keeping with advances that have been made in the development of cancer molecular biology. The present study aimed to investigate the synergistic effects of the abilities of the hemagglutinin neuraminidase protein of Newcastle disease virus (NDV), the pro-apoptotic factor apoptin from chicken anaemia virus, and the interferon-γ inducer interleukin-18 (IL-18) in antagonizing liver cancer. Therefore, a recombinant DNA plasmid expressing the three exogenous genes, VP3, IL-18 and hemagglutinin neuraminidase (HN), was constructed. Flow cytometry, acridine orange/ethidium bromide staining and analysis of caspase-3 activity were performed in H22 cell lines transfected with the recombinant DNA plasmid. In addition, 6-week-old C57BL/6 mice were used to establish a H22 hepatoma-bearing mouse model. Mice tumor tissue was analyzed by immunohistochemistry and scanning electron microscopy. The results of the present study revealed that the recombinant DNA vaccine containing the VP3, IL-18 and HN genes inhibited cell proliferation and induced autophagy via the mitochondrial pathway in vivo and in vitro.

Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality. Chemotherapy resistance remains a major challenge for treating advanced CRC. Therefore, the identification of targets that induce drug resistance is a priority for the development of novel agents to overcome resistance. Dragon (also known as RGMb) is a member of the repulsive guidance molecule (RGM) family. We previously showed that Dragon expression increases with CRC progression in human patients. In the present study, we found that Dragon inhibited apoptosis and increased viability of CMT93 and HCT116 cells in the presence of oxaliplatin. Dragon induced resistance of xenograft tumor to oxaliplatinin treatment in mice. Mechanistically, Dragon inhibited oxaliplatin-induced JNK and p38 MAPK activation, and caspase-3 and PARP cleavages. Our results indicate that Dragon may be a novel target that induces drug resistance in CRC.

A Rapid and Accurate Method to Evaluate Helicobacter pylori Infection, Clarithromycin Resistance, and CYP2C19 Genotypes Simultaneously From Gastric Juice.

Because Helicobacter pylori (H pylori) would cause carcinogenesis of the stomach, we need sufficient information for deciding on an appropriate strategy of eradication. Many factors affect the efficacy of eradication including antimicrobial resistance (especially clarithromycin resistance) and CYP2C19 polymorphism. This study was to survey the efficiency of gastric juice for detecting H pylori infection, clarithromycin resistance, and CYP2C19 polymorphism.The specimens of gastric juice were collected from all patients while receiving gastroscopy. DNA was extracted from gastric juice and then urease A and cag A were amplified by polymerase chain reaction (PCR) for detecting the existence of H pylori. By PCR-restriction fragment length polymorphism (PCR-RFLP), the 23S rRNA of H pylori and CYP2C19 genotypes of host were examined respectively. During endoscopy examination, biopsy-based specimens were also collected for rapid urease test, culture, and histology. The blood samples were also collected for analysis of CYP2C19 genotypes. We compared the results of gastric juice tests with the results of traditional clinical tests.When compared with the results from traditional clinical tests, our results from gastric juice showed that the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and accuracy to detect H pylori infection were 92.1% (105/114), 92.9% (143/154), 90.5% (105/116), 94.1% (143/152), and 92.5% (248/268), respectively. The SEN, SPE, PPV, and NPV to detect clarithromycin resistance were 97.3% (36/37), 91.5% (43/47), 90.0% (36/40), and 97.7% (43/44), respectively. By using PCR-RFLP, the consistency of human CYP2C19 gene polymorphism from blood samples and gastric juice was as high as 94.9% (149/157).The manipulated gastric juice is actually an effective diagnostic sample for evaluation of H pylori existence, clarithromycin resistance, and host CYP2C19 polymorphism.

Chinese physicians' perceptions of fecal microbiota transplantation.

AIM: To explore Chinese physicians' perceptions towards fecal microbiota transplantation (FMT) and to provide information and an assessment of FMT development in China. METHODS: A self-administered questionnaire was developed according to the FMT practice guidelines and was distributed to physicians in hospitals via Internet Research Electronic Data Capture (REDcap) software and electronic mails to assess their attitudes toward and knowledge of FMT. The questionnaire included a brief introduction of FMT that was followed by 20 questions. The participants were required to respond voluntarily, under the condition of anonymity and without compensation. Except for the fill-in-the-blank questions, all of the other questions were required in the REDcap data collection systems, and the emailed questionnaires were completed based on eligibility. RESULTS: Up to December 9, 2014, 844 eligible questionnaires were received out of the 980 distributed questionnaires, with a response rate of 86.1%. Among the participants, 87.3% were from tertiary hospitals, and there were 647 (76.7%) gastroenterologists and 197 (23.3%) physicians in other departments (non-gastroenterologists). Gastroenterologists' awareness of FMT prior to the survey was much higher than non-gastroenterologists' (54.3 vs 16.5%, P < 0.001); however, acceptance of FMT was not statistically different (92.4 vs 87.1%, P = 0.1603). Major concerns of FMT included the following: acceptability to patients (79.2%), absence of guidelines (56.9%), and administration and ethics (46.5%). On the basis of understanding, the FMT indications preferred by physicians were recurrent Clostridium difficile infection (86.7%), inflammatory bowel disease combined with Clostridium difficile infection (78.6%), refractory ulcerative colitis (70.9%), ulcerative colitis (65.4%), Crohn's disease (59.4%), chronic constipation (43.7%), irritable bowel syndrome (39.1%), obesity (28.1%) and type 2 diabetes (23.9%). For donor selection, the majority of physicians preferred individuals with a similar gut flora environment to the recipients. 76.6% of physicians chose lower gastrointestinal tract as the administration approach. 69.2% of physicians considered FMT a safe treatment. CONCLUSION: Chinese physicians have awareness and a high acceptance of FMT, especially gastroenterologists, which provides the grounds and conditions for the development of this novel treatment in China. Physicians' greatest concerns were patient acceptability and absence of guidelines.

Syntheses and preliminary evaluation of [(18) F]AlF-NOTA-G-TMTP1 for PET imaging of high aggressive hepatocellular carcinoma.

The goal of this study is to evaluate a new (18) F-labeled imaging agent for diagnosing high metastatic (aggressive) hepatocellular carcinoma using positron emission tomography (PET). The new (18) F-labeled imaging agent [(18) F]AlF-NOTA-G-TMTP1 was synthesized and radiolabeled with (18) F using NOTA-AlF chelation method. The tumor-targeting characteristics of [(18) F]AlF-NOTA-G-TMTP1 was assessed in HepG2, SMCC-7721, HCC97L and HCCLM3 xenografts. The total synthesis time was about 20 min with radiochemical yield of 25 ± 6%. The specific activity was about 11.1-14.8 GBq/µmol at the end of synthesis based on the amount of peptide used and the amount of radioactivity trapped on the C18 column. The log P value of [(18) F]AlF-NOTA-G-TMTP1 was -3.166 ± 0.022. [(18) F]AlF-NOTA-G-TMTP1 accumulated in SMCC-7721 and HCCLM3 tumors (high metastatic potential) in vivo and result in tumor/muscle (T/M) ratios of 4.5 ± 0.3 and 4.7 ± 0.2 (n = 4) as measured by PET at 40 min post-injection (p.i.). Meanwhile, the tumor/muscle (T/M) ratios of HepG2 and HCC97L tumors (low metastatic potential) were1.6 ± 0.3 and 1.8 ± 0.4. The tumor uptake of [(18) F]AlF-NOTA-G-TMTP1 could be inhibited 61.9% and 57.6% by unlabeled G-TMTP1 in SMCC-7721 and HCCLM3 xenografts at 40 min p.i., respectively. Furthermore, [(18) F]AlF-NOTA-G-TMTP1 showed pretty low activity in the liver and intestines in all tumor bearing mice, such in vivo distribution pattern would be advantageous for the detection of hepatic carcinoma. Overall, [(18) F]AlF-NOTA-G-TMTP1 may specifically target high metastatic or/and aggressive hepatocellular carcinoma with low background activity and, therefore, holds the potential to be used as an imaging agent for detecting tumor lesions within the liver area. Copyright © 2016 John Wiley & Sons, Ltd.

Attenuated effects of Jianpi Qushi herbs on patients receiving FOLFOX4 after colorectal cancer surgery: A meta-analysis.

OBJECTIVE: To systematically review the attenuating effects of invigorating Pi (Spleen) and eliminating dampness (Jianpi Qushi, JPQS) herbs on post-operational colorectal cancer patients receiving FOLFOX4 [5-fluorouracil (5-FU) + folinic acid + oxaliplatin] treatment. METHODS: China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database, PubMed/MEDLINE, EMBASE, and the Cochrane Library databases (up to May 2014) were searched in English or Chinese, and clinical trials with specifific inclusion criteria were collected. Data were analyzed by using Stata 12. RESULTS: The meta-analysis comprised 8 randomized clinical studies of 449 patients (238 in the treatment group and 211 in the control group). The results showed that JPQS herbs could improve the quality of life for post-operational colorectal cancer patients receiving FOLFOX4 [weighted mean difference (WMD) = 8.883, 95% confifidence interval (CI): 5.548 to 12.217]; alleviate the symptoms defifined by Chinese medicine [odds ratio (OR) = 5.741, 95% CI: 3.683 to 8.947]; and reduce the incidence rate of neutropenia [relative risk (RR) = 0.669, 95% CI: 0.503 to 0.888], decreased hemoglobin (RR = 0.654, 95% CI: 0.464 to 0.922), diarrhea (RR = 0.427, 95% CI: 0.275 to 0.662), nausea and vomiting (RR = 0.502, 95% CI: 0.390 to 0.648), and neurotoxic reactions (RR = 0.752, 95% CI: 0.595 to 0.951); however, the results showed no signifificant difference in the incidence rate of thrombocytopenia or liver and kidney dysfunction. CONCLUSION: JPQS herbs can improve the quality of life for patients undergoing FOLFOX4 treatment after colorectal cancer surgery, relieve symptoms, and somewhat reduce the adverse effects of FOLFOX4 regimen.

Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy enhances real-time in vivo diagnosis of adenomatous polyps during colonoscopy.

Colorectal cancer can be prevented if detected early (e.g., precancerous polyps-adenoma). Endoscopic differential diagnosis of hyperplastic polyps (that have little or no risk of malignant transformation) and adenomas (that have prominent malignant latency) remains an unambiguous clinical challenge. Raman spectroscopy is an optical vibrational technique capable of probing biomolecular changes of tissue associated with neoplastic transformation. This work aims to apply a fiber-optic simultaneous fingerprint (FP) and high wavenumber (HW) Raman spectroscopy technique for real-time in vivo assessment of adenomatous polyps during clinical colonoscopy. We have developed a fiber-optic Raman endoscopic technique capable of simultaneously acquiring both the FP (i.e., 800-1800 cm(-1)) and HW (i.e., 2800-3600 cm(-1)) Raman spectra from colorectal tissue subsurface (<200 µm) for real-time assessment of colorectal carcinogenesis. In vivo FP/HW Raman spectra were acquired from 50 patients with 17 colorectal polyps during clinical colonoscopy. Prominent Raman spectral differences (p < 0.001) were found between hyperplastic (n = 118 spectra), adenoma (n = 184 spectra) that could be attributed to changes in inter- and intra-cellular proteins, lipids, DNA and water structures and conformations. Simultaneous FP/HW Raman endoscopy provides a diagnostic sensitivity of 90.9% and specificity of 83.3% for differentiating adenoma from hyperplastic polyps, which is superior to either the FP or HW Raman technique alone. This study shows that simultaneous FP/HW Raman spectroscopy technique has the potential to be a clinically powerful tool for improving early diagnosis of adenomatous polyps in vivo during colonoscopic examination.

Mechanisms of pyruvate kinase M2 isoform inhibits cell motility in hepatocellular carcinoma cells.

AIM: To investigate biological mechanisms underlying pyruvate kinase M2 isoform (PKM2) regulation of cell migration and invasion in hepatocellular carcinoma cells. METHODS: HepG2 and Huh-7 hepatocellular carcinoma cell lines were stably transfected and cultured in DMEM (HyClone, Logan, UT, United States). To investigate the effects of PKM2 on cellular proliferation, hepatocellular carcinoma cells were subjected to the Cell Counting Kit-8 (Dojindo, Kamimashiki-gun, Kumamoto, Japan). And investigate the effects of PKM2 on cell signal pathway related with migration and invasion, Western immunoblotting were used to find out the differential proteins. All the antibody used was purchaseed from Cell Signal Technology. In order to explore cell motility used Transwell invasion and wound healing assays. The transwell plate with 0.5 mg/mL collagen type I (BD Bioscience, San Jose, CA)-coated filters. The wound-healing assay was performed in 6-well plates. Total RNA was extracted using TRIzol reagent (Invitrogen, CA, United States) and then reverse transcription was conducted. Quantitative reverse transcription-polymerase chain reaction (PCR) analysis was performed with the ABI 7500 real-time PCR system (Applied Biosystems). We further use digital gene expression tag profiling and identification of differentially expressed genes. RESULTS: The cells seeded in four 96-well plates were measured OD450 by conducted Cell Counting Kit-8. From this conduction we observed that both HepG2 and Huh-7 hepatocellular carcinoma cells with silenced PKM2 turn on a proliferate inhibition; however, cell migration and invasion were enhanced compared with the control upon stimulation with epidermal growth factor (EGF). Our results indicate that the knockdown of PKM2 decreased the expression of E-cadherin and enhanced the activity of the EGF/EGFR signaling pathway, furthermore up-regulate the subsequent signal molecular the PLCγ1 and extracellular signal-regulated kinase 1/2 expression in the hepatocellular carcinoma cell lines HepG2 and Huh-7, which regulates cell motility. These variations we observed were due to the activation of the transforming growth factor beta (TGFß) signaling pathway after PKM2 knockdown. We also found that the expression of TGFBRI was increased and the phosphorylation of Smad2 was enhanced. Taken together, our findings demonstrate that PKM2 can regulate cell motility through the EGF/EGFR and TGFß/TGFR signaling pathways in hepatocellular carcinoma cells. CONCLUSION: PKM2 play different roles in modulating the proliferation and metastasis of hepatocellular carcinoma cells, and this finding could help to guide the future targeted therapies.

Dragon (repulsive guidance molecule b, RGMb) is a novel gene that promotes colorectal cancer growth.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. Dragon (RGMb), a member of the repulsive guidance molecule (RGM) family, has been recently identified as a co-receptor for bone morphogenetic protein (BMP) signaling, but the role of Dragon in CRC development is undefined. Here, we show that Dragon expression was increased in colon cancer tissues compared to control tissues in CAC mouse model and in human patients. Dragon promoted proliferation of CT26.WT and CMT93 colon cancer cells and accelerated tumor growth in the xenograft mouse model. Dragon's action on colon cancer development was mediated via the BMP4-Smad1/5/8 and Erk1/2 pathways. Therefore, our results have revealed that Dragon is a novel gene that promotes CRC growth through the BMP pathway. Dragon may be exploited as a potential therapeutic target for CRC treatment.