Downregulation of Wnt3 Suppresses Colorectal Cancer Development Through Inhibiting Cell Proliferation and Migration.

The aberrant expression of Wnt3 has linked to several types of human malignancies. However, it is not known for its role in tumorigenesis of colorectal cancer (CRC). Herein, we show that Wnt3 is upregulated in human CRC tissues and is essential for the CRC progression. Knockdown of Wnt3 in human CRC cells delayed tumor formation in nude mouse xenografts through silencing of canonical Wnt pathway and glycolysis. We further found that silencing of Wnt3 enhanced the sensitivity of CRC cells to cisplatin through inducing apoptotic cell death. Taken together, it demonstrates that Wnt3 is a novel clinical biomarker for the detection of CRC and plays an important role in colorectal tumorigenesis. Therefore, downregulation of Wnt3 will be a valuable strategy in CRC treatment.

Knockdown of ZFPL1 results in increased autophagy and autophagy­related cell death in NCI­N87 and BGC­823 human gastric carcinoma cell lines.

Macroautophagy, which will hereafter be referred to as autophagy, is an evolutionarily conserved process, during which cells recycle and remove damaged organelles and proteins in response to cellular stress. However, the mechanisms underlying the regulation of autophagy remain to be fully elucidated. The present study demonstrated that knockdown of zinc finger protein like 1 (ZFPL1) induces autophagy and increases autophagic cell death in NCI­N87 and BGC­823 human gastric carcinoma cell lines. To examine the role of ZFPL1 in gastric carcinoma cells, ZFPL1 expression was downregulated by lentiviral infection. Zinc finger domain­FLAG was used to compete with ZFPL1 for golgin A2/GM130 binding. Autophagy was analyzed by red fluorescent protein­microtubule­associated protein 1A/1B­light chain 3 (LC3) puncta, LC3I to LC3II conversion, and p62 expression. The results demonstrated that knockdown of ZFPL1 was able to significantly increase cell death rate. However, ZFPL1 knockdown exerted almost no effect on the expression of apoptosis­associated markers, including B cell lymphoma 2 (Bcl­2), Bcl­x, Bcl­2­associated X protein, BH3 interacting domain death agonist, p53, and the classical caspase family members, caspase­3, caspase­8 and caspase­9. An endogenous ZFPL1­GM130 association was identified in NCI­N87 cells and BGC­823 cells by co­immunoprecipitation. Furthermore, cell death was restricted following treatment of ZFPL1 knockdown cells with an autophagy inhibitor. Therefore, knockdown of ZFPL1 expression may induce cell death via autophagy, rather than apoptosis. These results suggest that ZFPL1 may serve an important role in regulating autophagy in NCI­N87 and BGC­823 cells.

Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer: An Updated Meta-Analysis Based on GWAS Results.

Genome-wide association studies (GWASs) and a number of case-control studies have suggested that several single nucleotide polymorphisms (SNPs), rs7837328, rs7014346, rs6983267, rs10505477 on CASC8 gene and rs4939827, rs4464148, rs12953717 on SMAD7 gene are significantly correlated with the susceptibility to colorectal cancer (CRC). For the sake of clarifying the association, a meta-analysis was conducted and population heterogeneity was considered in the study.A total of 34 articles including 90 studies (168,471 cases and 163,223 controls) that evaluated the relationship between the CASC8, SMAD7 genes and the risk of CRC under the allelic model were reviewed. Also subgroup analysis was performed by ethnicity (Caucasian, Asian, and African) and all of the analyses were implemented in R 3.2.1 software.Pooled data from the meta-analysis revealed that the A allele of rs7837328, the A allele of rs7014346, the G allele of rs6983267, the A allele of rs10505477, the T allele of rs4939827, the T of rs4464148, and the T of rs12953717 were significantly associated with an increased risk of CRC under the allelic model. Additionally, subgroup analyses of 6 SNPs by ethnicity (rs4464148 excepted) witnessed that the A allele of rs7837328, the G allele of rs6983267, and the T of rs12953717 were notably associated with an increased risk of CRC among Caucasian and Asian. Furthermore, the A allele of rs7014346, the A allele of rs10505477, and the T allele of rs4939827 were significantly related with an elevated risk of CRC only among Caucasian.Our study suggested that for CASC8 gene, SNP of rs7837328 and rs6983267 are risk factors for CRC among both Caucasian and Asian whereas rs7014346 and rs10505477 are risky gene polymorphisms only among Caucasian. For SMAD7 gene, rs4939827 and rs4464148 are risk factors for CRC among Caucasian whereas rs12953717 could elevate the susceptibility to CRC in both Caucasian and Asian.

[Experiences of scarless laparoscopic radical resection of rectal cancer].

OBJECTIVE: To explore the feasibility and safety of scarless laparoscopic radical resection of rectal cancer. METHODS: Clinical data of 26 patients who underwent scarless laparoscopic radical resection of rectal cancer from January 2011 to June 2013 were retrospectively analyzed. Lymph node dissection and transection of proximal and distal colon were performed in the conventional manner of total mesorectal excision (TME). The distal rectum 2 cm away from the tumor was closed with a linear stapler, and was pulled out through the anus. The specimen was extracted through the Alexis. The rectal opening was reclosed with a linear stapler. End-to-end colorectal anastomosis was performed using the double-stapling technique. RESULTS: The operation time was (126±35) min. The intraoperative blood loss was (33±61) ml. The number of harvested lymph nodes was 17.0±5.6. The time to first bowel movement was (2.7±1.3) d. The postoperative hospital stay was (7.9±2.6) d. Only one case developed anastomotic hemorrhage. CONCLUSION: Scarless laparoscopic radical resection of rectal cancer is feasible.

Prevalence of rheumatic symptoms, rheumatoid arthritis, ankylosing spondylitis, and gout in Shanghai, China: a COPCORD study.

OBJECTIVE: To carry out a cross-sectional survey on prevalence of musculoskeletal symptoms, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and gout. METHODS: In Shanghai, 4 communities comprising 7603 inhabitants over 15 years of age in an urban population were randomly selected from 13 communities. Interviews were conducted from September 1997 to March 1998 by trained physicians using the COPCORD Core Questionnaire. Physical and radiographic examinations and serologic tests were carried out when required to classify categories of rheumatic diseases. The diagnoses of RA, systemic lupus erythematosus (SLE), and gout were based on American Rheumatism Association criteria. The diagnosis of AS strictly followed the modified New York criteria of 1984. Crude prevalence rates were standardized according to a standard Chinese population for age and sex structure. RESULTS: A total of 6584 adults (3394 women, 3190 men) were interviewed, and response rate was 86.6%. The age and sex standardized prevalence rate of rheumatic symptoms at any site amounted to 13.3% (95% CI 12.5-14.1%). Symptoms occurred more frequently in the following sites: knee 7.0% (95% CI 6.4-7.6%), lower back 5.6% (95% CI 5.0-6.2%), shoulder 4.7% (95% CI 4.2-5.2%), and neck 2.4% (95% CI 2.0-2.8%). Women complained of rheumatic symptoms more frequently than men. The standardized rates of RA, AS, gout, symptomatic knee osteoarthritis, and soft tissue rheumatism were 0.28% (95% CI 0.15-0.41%), 0.11% (95% CI 0.03-0.19%), 0.22% (95% CI 0.11-0.33%), 4.1% (95% CI 3.6-4.6%), and 3.4% (95% CI 3.0-3.8%), respectively. Two cases of SLE, one case of dermatomyositis, and one case of systemic sclerosis were found. CONCLUSION: Compared with rates in European and Western countries the prevalence rates of RA, AS, and gout are low in Shanghai, China, although the prevalence rates of rheumatic symptoms are high.

[The extraction and effects on mouse lymphocyte proliferation of immunoregulation components from Lysimachia hemsleyana].

OBJECTIVE: To study the effects of extracted fractions from the whole plants of Lysimachia hemsleyana Maxim on the proliferation ability of lymphocytes in mice in vitro. METHODS: We extracted the components by using of ethanol, ether from petroleum, chloroform, ethyl acetate and n-butanol, successively then study them on the proliferation of lymphocytes in mice. RESULTS: The n-butanol fraction obviously inhibited the proliferation of spleen lymphocytes induced by LPS, bilaterally regulated the T lymphocyte proliferation induced by ConA. The chloroform fraction markedly enhanced the lymphocytes proliferation induced by ConA or LPS. CONCLUSION: The results suggested that n-butanol fraction and chloroform fraction from Lysimachia hemsleyana possibly maybe have immunoregulation effects.

[Clinical study on effect of Agkistrodon antithrombogenase in auxiliary treatment of rheumatoid arthritis].

OBJECTIVE: To explore the clinical effect of Agkistrodon antithrombogenase (AAT) in the treatment of rheumatoid arthritis (RA) and its possible mechanism. METHODS: Besides the conventional non-steroid anti-inflammatory agents and disease-modifying anti-rheumatic drug, patients were treated supplementally with intravenous injection of AAT. The intracutaneous test showed allergic to AAT patients were treated with Salvia injection and taken as control group. Changes of related clinical indexes in the two groups were observed. RESULTS: After 3 weeks treatment, condition of patients in both groups were improved clinically in joint swollen index, joint tenderness index, morning stiffness time, pain assessment (VAS) and health assessment questionnaire (HAQ) on daily life activity as well as ESR level (P < 0.05 or P < 0.01), with the VAS, HAQ and fibrinogen levels more significantly improved than those of control (P < 0.05 or P < 0.01), and the total effective rate higher in the AAT treated group than those in the control group (P < 0.05). CONCLUSION: AAT has good effect on easing clinical symptoms of RA possibly through anti-inflammation and improving the microcirculation with less toxic and adverse reaction, so is worthy of recommendation.

[The effects of n-butanol fraction of Lysimachia hemsleyana on the activities of lymphocytes in mice].

OBJECTIVE: To study the effects of n-butanol fraction from the whole plants (Lysimachia hemsleyana) on the phagocytic activities of the peritoneal macrophage, production of interleukin-2. METHODS: We extracted the components with ethanol, acetic ether, n-butanol and chloroform, then studied the n-butanol fraction on the phagocytic activities of the peritoneal macrophage, production of interleukin-2 (IL-2) from splenocytes induced by ConA in mice in vitro. RESULTS: n-Butanol fraction of an ethanol extract of air-dried herbs bilaterally regulated the IL-2 production from splenocytes induced by ConA, and enhanced the phagocytic activities of activated mouse peritoneal macrophages. CONCLUSION: The results suggest that Lysimachia hemsleyana may has an immunoregulation effect and may be an potential agent in the treatment of the inflammatory pathological process and some autoimmune diseases.