Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis-Related Th17 Response by Host-Microbe Retinoic Acid Biosynthesis.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.

Resveratrol Improves Brain-Gut Axis by Regulation of 5-HT-Dependent Signaling in the Rat Model of Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is at high risk of co-morbid depression and anxiety, which reduces patients' quality of life and increases the burden of health care costs. However, the pathophysiological mechanisms responsible for IBS still remain unknown. This study investigated the effects of resveratrol on stress-related depression, anxiety, intestinal and visceral dysfunction in rat model of IBS. Rats received chronic acute combining stress (CACS) for 22 days exhibited depression/anxiety-like behavior, visceral hypersensitivity and altered intestinal motility, as measured by the forced swimming, marble bury, abdominal withdrawal reflex (AWR) and intestinal tract motility (ITM) tests. These abnormalities were accompanied by reduced 5-hydroxytryptamine (5-HT) level in the hippocampus and increased 5-HT expression in the gut (ileum and colon) after CACS. Chronic treatment of IBS rats with resveratrol dose-dependently normalized CACS-induced both central nervous and peripheral dysfunction, which were consistent with its differentially regulating 5-HT contents in the brain and intestine. Pretreatment with the 5-HT1A receptor antagonist NAN-190 hydrobromide (NAN-190) prevented such effects. While sub-threshold of 5-HT1A receptor agonist 8-OH-DPAT potentiated the effects of low dose of resveratrol (10 mg/kg) on CACS-related behavioral abnormalities. Furthermore, resveratrol markedly increased PKA, p-cAMP-response element binding protein (p-CREB) and brain derived neurotrophic factor (BDNF) expression in the hippocampus of IBS rats, while decreased PKA, pCREB and BDNF levels were found in the ileum and colon. These effects were prevented by NAN-190, which were consistent with the behavioral changes. The present results suggested that resveratrol improved anti-IBS-like effects on depression, anxiety, visceral hypersensitivity and intestinal motility abnormality through regulating 5-HT1A-dependent PKA-CREB-BDNF signaling in the brain-gut axis.

Outcomes of furazolidone- and amoxicillin-based quadruple therapy for Helicobacter pylori infection and predictors of failed eradication.

AIM: To evaluate the outcomes of furazolidone- and amoxicillin-based quadruple therapy for treatment of Helicobacter pylori (H. pylori) infection and identify predictors of failed eradication. METHODS: Patients with H. pylori infection treated with furazolidone, amoxicillin, bismuth, and proton pump inhibitor therapy (January 2015 to December 2015) who received the 13C-urea breath test > 4 wk after treatment were evaluated. Demographic and clinical data including prior H. pylori treatment attempts, medication adherence, alcohol and cigarette consumption during therapy, and treatment-related adverse events were recorded by reviewing medical records and telephone surveys. H. pylori eradication rates for overall and subgroups were evaluated. Multivariate analysis was performed to identify independent predictors of failed H. pylori eradication. RESULTS: Of the 992 patients treated and retested for H. pylori infection, the overall eradication rate was 94.5% [95% confidence interval (CI): 94.1%-95.9%]. H. pylori eradication rate of primary therapy was 95.0% (95%CI: 93.5%-96.5%), while that of rescue therapy was 91.3% (95%CI: 86.8%-95.8%). Among the 859 patients who completed the study protocol, 144 (17%) reported treatment-related adverse events including 24 (3%) leading to premature discontinuation. On multivariate analysis, poor medication adherence [adjusted odds ratio (AOR) = 6.7, 95%CI: 2.8-15.8], two or more previous H. pylori treatments (AOR = 7.4, 95%CI: 2.2-24.9), alcohol consumption during therapy (AOR = 4.4, 95%CI: 1.5-12.3), and possibly smoking during therapy (AOR = 1.9, 95%CI: 0.9-4.3) were associated with failed H. pylori eradication. CONCLUSION: Furazolidone- and amoxicillin-based quadruple therapy for H. pylori infection in an area with a high prevalence of clarithromycin resistance demonstrated high eradication rates as primary and rescue therapies with a favorable safety profile. Patient education targeting abstinence from alcohol during therapy and strict medication adherence may further optimize H. pylori eradication.

trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis.

Background: Irritable bowel syndrome (IBS) is a functional disorder characterized by abdominal pain and abnormalities in defecation associated with psychiatric disorders such as depression and anxiety due to the dysfunction of brain-gut axis. This study aims to determine whether trans-Resveratrol affects chronic-acute combined stress (CACS)-induced IBS-like symptoms including depression, anxiety and intestinal dysfunction. Methods: ICR male mice were exposed to the CACS for 3 weeks. trans-Resveratrol were administrated daily (2.5, 5, and 10 mg/kg, i.g.) 30 min before CACS. Behavioral tests were performed to evaluate the treatment effects of trans-Resveratrol on IBS. Hippocampus tissues were collected and processed Golgi staining and immuno-blot analysis. Ileum and colon tissues were collected and processed Hematoxylin and Eosin staining and immuno-blot analysis. Results: Administration with trans-Resveratrol before CACS for 3 weeks significantly reversed CACS-induced depression- and anxiety-like behaviors and intestinal dysfunction in mice, which implied a crucial role of trans-Resveratrol in treatment of IBS-like disorder. Furthermore, trans-Resveratrol improved hippocampal neuronal remodeling, protected ileal and colonic epithelial barrier structure against CACS insults. The further study suggested that trans-Resveratrol normalized phosphodiesterases 4A (PDE4A) expression and CREB-BDNF signaling that were disturbed by CACS. The increased pCREB and BDNF expression in the hippocampus were found, while decreased pCREB and BDNF levels were observed after treatment with trans-Resveratrol. Conclusions: The dual effects of trans-Resveratrol on stress-induced psychiatric and intestinal dysfunction may be related to normalization of PDE4A expression and subsequent pCREB-BDNF signaling in the hippocampus, ileum and colon.

HOTAIR induces the ubiquitination of Runx3 by interacting with Mex3b and enhances the invasion of gastric cancer cells.

BACKGROUND: Long non-coding RNAs (LncRNAs) exert their functions mainly by binding to their corresponding proteins. Runt-related transcription factor 3 (Runx3) is an important transcription factor that functions as a tumor suppressor in gastric cancer. Whether there is an interplay between LncRNAs and Runx3 remains unclear. METHODS: RPISeq was applied to screen the LncRNAs that potentially bind to Runx3. The interaction between LncRNA HOX antisense intergenic RNA (HOTAIR) and Runx3 was validated by RNA Immunoprecipitation and RNA pull-down assays. The role of Mex3b in the ubiquitination of Runx3 induced by HOTAIR was assessed by immunoprecipitation. Pearson's correlation between HOTAIR mRNA expression and Runx3 protein expression was analyzed. Cell migration and invasion were explored by transwell assays. RESULTS: We found that HOTAIR was bound to Runx3 protein and identified the fragment of HOTAIR spanning 1951-2100 bp as the specific binding site. In addition, mex-3 RNA binding family member B (Mex3b) was an E3 ligase involved in HOTAIR-induced ubiquitous degradation of Runx3. Silencing the expression of HOTAIR or Mex3b attenuated the degradation of Runx3. In human gastric cancer tissues, HOTAIR was negatively associated with the expression level of Runx3 protein (Pearson coefficient - 0.501, p = 0.025). Inhibition of HOTAIR significantly suppressed gastric cancer cell migration and invasion through upregulating claudin1, which could be reversed by co-deficiency of Runx3. CONCLUSIONS: These results uncovered the novel interaction between HOTAIR and Runx3, and provided potential therapeutic targets on the metastasis of gastric cancer.

Two-tube method for treatment of spontaneous esophageal rupture and concomitant mediastinal infection.

Objective Spontaneous esophageal rupture (SER) is a rare but life-threatening condition with high mortality. The prognosis of patients with SER treated with surgical intervention or the traditional "three-tube" method is controversial. Thus, the aim of this study was to evaluate the clinical efficacy, feasibility, and safety of a new "two-tube" method involving a trans-fistula drainage tube and a three-lumen jejunal feeding tube for the treatment of SER without concomitant pleural rupture. Methods From January 2007 to June 2016, patients with SER and managed with the "two-tube" method or other methods were retrospectively analyzed. Data collected included initial presentation, procedure time, duration of treatment, numbers of patients with eventual healing of leaks, and complications. Results The average procedure time for the "two-tube" method was 22.1 ± 5.5 minutes. In comparison with the control method, the "two-tube" method had a similar diagnosis time (3.6 ± 1.4 vs. 3.4 ± 1.4 days) but a significantly higher successful closure rate (94.4% vs. 63.6%) and shorter treatment time (38.2 ± 5.6 vs. 53.6 ± 16.9 days). No complications associated with performance of the "two-tube" method occurred. Conclusion The "two-tube" method is an effective and safe approach for patients with SER.

Impact of preprocedure simethicone on adenoma detection rate during colonoscopy: a multicenter, endoscopist-blinded randomized controlled trial.

BACKGROUND AND STUDY AIMS: Ideal bowel preparation for colonoscopy requires complete removal of fluid and foam from the colon. Polyethylene glycol (PEG) is widely used for bowel preparation, with antifoaming agents such as simethicone commonly used in combination with PEG. Data on the effect of simethicone on the adenoma detection rate (ADR) were limited. This study therefore aimed to investigate whether preprocedure simethicone could increase the ADR. PATIENTS AND METHODS: This was a prospective, multicenter, endoscopist-blinded randomized controlled trial involving consecutive patients who underwent colonoscopy in six centers in China. Patients were randomly assigned to one of two groups: PEG plus simethicone or PEG alone. The primary outcome was ADR; secondary outcomes were quality of bowel preparation, measured by the Boston bowel preparation scale (BBPS) and bubble scores. RESULTS: 583 patients were included. More adenomas were detected in the PEG plus simethicone group than in the PEG alone group (ADR 21.0 % vs. 14.3 %, P = 0.04; advanced ADR 9.0 % vs. 7.0 %, P = 0.38). The mean number of adenomas detected was 2.20 ±â€Š1.36 vs. 1.63 ±â€Š0.89 (P = 0.02). Patients in the PEG plus simethicone group showed better bowel cleansing efficacy: BBPS ≥ 6 in 88.3 % vs. 75.2 % (P < 0.001) and bubble scores of 1.00 ±â€Š1.26 vs. 3.98 ±â€Š2.50 (P < 0.001). Abdominal bloating was reported less frequently in the PEG plus simethicone group (7.8 % vs. 19.7 %, P < 0.001) than in the PEG alone group. CONCLUSION: Combined use of PEG and simethicone is associated with a significantly increased ADR in a Chinese population.

Klebsiella pneumoniae invasive liver abscess syndrome with purulent meningitis and septic shock: A case from mainland China.

We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient's condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in mainland China. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease.

Metformin Is Associated With Slightly Reduced Risk of Colorectal Cancer and Moderate Survival Benefits in Diabetes Mellitus: A Meta-Analysis.

To systematically assess the effect of metformin on colorectal cancer (CRC) risk and mortality in type 2 diabetes mellitus (T2DM) patients. We conducted a systematic search of PubMed, Web of Science, and the Cochrane Library databases for relevant articles before August 2015. Two investigators identified and extracted data independently. We adopted adjusted estimates to calculate summary estimates with 95% confidence interval (CI) using either a fixed-effects or a random-effects model. Subgroup and sensitivity analyses were conducted to evaluate the robustness of the pooled results. The risk of publication bias was assessed by examining funnel plot asymmetry as well as Begg test and Egger test. Fifteen studies on CRC incidence and 6 studies on CRC survival were finally included in our meta-analysis. The pooled odds ratio (OR) of observational studies illustrated that a slight 10% reduction of CRC incidence was associated with metformin use (OR = 0.90, 95% CI: 0.85-0.96). Furthermore, the pooled hazard ratio (HR) revealed an improved survival outcome for metformin users in CRC patients compared to nonusers (HR = 0.68, 95% CI: 0.58-081). There was no publication bias across studies. Our meta-analysis demonstrated that metformin therapy could slightly reduce CRC incidence and moderately improve the survival outcomes in patients with T2DM. More prospective studies are warranted to certify this protective association.

How reliable is the Ki-67 cytological index in grading pancreatic neuroendocrine tumors? A meta-analysis.

OBJECTIVE: To investigate the accuracy of the cytological Ki-67 index in distinguishing intermediate and high-grade (G2 + G3) from low-grade (G1) pancreatic neuroendocrine tumors (PNETs). METHODS: Two investigators independently searched databases to identify eligible studies using the following term: ('Ki-67') AND ('pancreatic endocrine tumor' OR 'pancreatic neuroendocrine tumor' OR 'pancreatic endocrine tumour' OR 'pancreatic neuroendocrine tumour' OR 'pancreatic endocrine tumors' OR 'pancreatic neuroendocrine tumors' OR 'pancreatic endocrine tumours' OR 'pancreatic neuroendocrine tumours'), and meta-analysis was performed to calculate the pooled sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). RESULTS: A total of 263 lesions from 13 studies were included in the study. The pooled sensitivity and specificity of Ki-67 (cut-off value: 2%) in the differential diagnosis of G2 + G3 from G1 PNETs were 64% and 87%, respectively. The pooled PLR, NLR and DOR were 3.96, 0.42 and 11.21, respectively. The area under the summary receiver operating characteristic curve (AUROC) was 0.8397. While the cut-off value of Ki-67 index was set as 5%, the sensitivity and specificity were increased up to 69% and 93%, respectively, and the AUROC was increased to 0.955. CONCLUSION: The cytological Ki-67 index is very useful in distinguishing intermediate and high-grade from low-grade PNETs, and a cut-off value of 5% had a better predictive value compared with that of 2%.

Endoscopic submucosal dissection for early gastric cancer in elderly patients: a meta-analysis.

BACKGROUND: The effectiveness of endoscopic submucosal dissection (ESD) has been increasingly reported. However, studies addressing the safety and application value of ESD in elderly patients with early gastric cancer (EGC) were still lacking. This meta-analysis was intended to evaluate the feasibility and safety of ESD in elderly patients with EGC. METHODS: A systematic search was conducted in PubMed, EBSCO, Cochrane Library, EMBASE, and Web of Science. Studies were screened out if data of elderly and non-elderly gastric cancer patients were reported separately. The qualities of included studies were assessed using Newcastle-Ottawa Quality Assessment Scale. The pooled odd ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Statistical analysis was conducted using the Review Manager 5.2 (Cochrane Collaboration, Oxford, UK). RESULTS: Nine studies (eight in Japan, one in China), including a total of 30,100 lesions, met the inclusion criteria. The "en bloc" and histological complete resection rates of the elderly and non-elderly groups were similar [OR, 0.98, 95 % CI, 0.56 to 1.71; P = 0.93 and OR, 0.79, 95 % CI, 0.58 to 1.07; P = 0.13, respectively]. As for procedure-related complications, similar perforation rates [OR, 1.19, 95 % CI, 0.94 to 1.51; P = 0.15], and bleeding rates [OR, 1.13, 95 % CI, 0.83 to 1.56); P = 0.43] between the elderly and non-elderly groups were observed. Whereas, the elderly patients had a higher procedure-related pneumonia rate compared with non-elderly ones [OR, 2.18, 95 % CI, 1.55 to 3.08; P < 0.01]. CONCLUSIONS: The ESD procedure appears to be a safe technique in elderly patients with EGC while appropriate approach should be taken to avoid procedure-related pneumonia.

Parkin represses 6-hydroxydopamine-induced apoptosis via stabilizing scaffold protein p62 in PC12 cells.

AIM: Parkin has been shown to exert protective effects against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in different models of Parkinson disease. In the present study we investigated the molecular mechanisms underlying the neuroprotective action of parkin in vitro. METHODS: HEK293, HeLa and PC12 cells were transfected with parkin, parkin mutants, p62 or si-p62. Protein expression and ubiquitination were assessed using immunoblot analysis. Immunoprecipitation assay was performed to identify the interaction between parkin and scaffold protein p62. PC12 and SH-SY5Y cells were treated with 6-OHDA (200 µmol/L), and cell apoptosis was detected using PI and Hoechst staining. RESULTS: In HEK293 cells co-transfected with parkin and p62, parkin was co-immunoprecipitated with p62, and parkin overexpression increased p62 protein levels. In parkin-deficient HeLa cells, transfection with wild-type pakin, but not with ligase activity-deficient pakin mutants, significantly increased p62 levels, suggesting that parkin stabilized p62 through its E3 ligase activity. Transfection with parkin or p62 significantly repressed ERK1/2 phosphorylation in HeLa cells, but transfection with parkin did not repress ERK1/2 phosphorylation in p62-knockdown HeLa cells, suggesting that p62 was involved in parkin-induced inhibition on ERK1/2 phosphorylation. Overexpression of parkin or p62 significantly repressed 6-OHDA-induced ERK1/2 phosphorylation in PC12 cells, and parkin overexpression inhibited 6-OHDA-induced apoptosis in PC12 and SH-SY5Y cells. CONCLUSION: Parkin protects PC12 cells against 6-OHDA-induced apoptosis via ubiquitinating and stabilizing scaffold protein p62, and repressing ERK1/2 activation.

[Searching for Rare Celestial Objects Automatically from Stellar Spectra of the Sloan Digital Sky Survey Data Release Eight].

There are many valuable rare and unusual objects in spectra dataset of Sloan Digital Sky Survey (SDSS) Data Release eight (DR8), such as special white dwarfs (DZ, DQ, DC), carbon stars, white dwarf main-sequence binaries (WDMS), cataclysmic variable (CV) stars and so on, so it is extremely significant to search for rare and unusual celestial objects from massive spectra dataset. A novel algorithm based on Kernel dense estimation and K-nearest neighborhoods (KNN) has been presented, and applied to search for rare and unusual celestial objects from 546 383 stellar spectra of SDSS DR8. Their densities are estimated using Gaussian kernel density estimation, the top 5 000 spectra in descend order by their densities are selected as rare objects, and the top 300 000 spectra in ascend order by their densities are selected as normal objects. Then, KNN were used to classify the rest objects, and simultaneously K nearest neighbors of the 5 000 rare spectra are also selected as rare objects. As a result, there are totally 21 193 spectra selected as initial rare spectra, which include error spectra caused by deletion, redden, bad calibration, spectra consisting of different physically irrelevant components, planetary nebulas, QSOs, special white dwarfs (DZ, DQ, DC), carbon stars, white dwarf main-sequence binaries (WDMS), cataclysmic variable (CV) stars and so on. By cross identification with SIMBAD, NED, ADS and major literature, it is found that three DZ white dwarfs, one WDMS, two CVs with company of G-type star, three CVs candidates, six DC white dwarfs, one DC white dwarf candidate and one BL Lacertae (BL lac) candidate are our new findings. We also have found one special DA white dwarf with emission lines of Ca II triple and Mg I, and one unknown object whose spectrum looks like a late M star with emission lines and its image looks like a galaxy or nebula.

Converting a microarray signature into a diagnostic test: a trial of custom 74 gene array for clarification and prediction the prognosis of gastric cancer.

BACKGROUND: Gastric cancer (GC) is associated with high mortality rates and an unfavorable prognosis at advanced stages. In addition, there are no effective methods for diagnosing gastric cancer at an early stage or for predicting the outcome for the purpose of selecting patient-specific treatment options. Therefore, it is important to investigate new methods for GC diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: To facilitate its use in a diagnostic setting, a group of 74 genes with diagnostic and prognostic information was translated into a customized microarray containing a reduced set of 1,042 probes suitable for high throughput processing. In this report, we demonstrate for the first time that the custom mini-array can be used as a reliable diagnostic tool in gastric cancer. With an AUC value of 0.565 (95% CI 0.305-0.825) indicating a perfect test, the sensitivity and specificity of diagnosis from the ROC curve were calculated to be 70% and 80%, respectively. CONCLUSIONS/SIGNIFICANCE: The data clearly demonstrate the reproducibility and robustness of the small custom-made microarray. The array is an excellent tool for classifying and predicting the outcome of disease in gastric cancer patients.

Cytomegalovirus: a probable cause of steroid-refractory ulcerative colitis.

Cytomegalovirus, regarded as a trigger of several autoimmune diseases, is an opportunistic pathogen. Patients with ulcerative colitis (UC) undergoing steroid treatment are susceptible to this infection. In the presence of cytomegalovirus, inflammation becomes more complex. Patients with active UC who are infected with cytomegalovirus are usually non-responders to steroid, while antiviral drugs could induce remission. Cytomegalovirus should be suggested as a probable cause of steroid-refractory UC based on the clinical data in the literatures.

Molecular evolutionary analysis of the duck MYOD gene family and its differential expression pattern in breast muscle development.

1. The objective of the research was to investigate the molecular evolutionary relationships between the duck myogenic determination factors (MYOD) gene family members and their roles in muscle development. 2. The four members of the duck MYOD gene family were cloned using RT-PCR, and their relative mRNA expression during duck muscle development was measured using qRT-PCR. 3. The results showed that MyoD and Myf5 clustered together, as did MyoG and MRF4 based on their complete amino acid sequence and the basic helix-loop-helix domain. Results of the evolutionary level analysis were consistent with that of the differential expression patterns during duck breast muscle development. As determined by qRT-PCR, MyoD and Myf5 were highly expressed in 22-day embryos, while MyoG and MRF4 expression was high in 14-day embryos. 4. We conclude that the entire MYOD gene family in the duck originated from a common ancestral gene and evolved after two duplication events. The roles of the MYOD gene family members in duck muscle development are similar to those in mammals.

Nuclear JAK2: form and function in cancer.

The conventional view of Janus kinase 2 (JAK2) is a nonreceptor tyrosine kinase which transmits information to the nucleus via the signal transducer and activator of transcriptions (STATs) without leaving the cytoplasm. However, accumulating data suggest that JAK2 may signal by exporting from cytoplasm to nucleus, where it guides the transcriptional machinery independent of STATs protein. Recent studies demonstrated that JAK2 is a crucial component of signaling pathways operating in the nucleus. Especially the latest landmark discovery confirmed that JAK2 goes into the nucleus and directly interacts with nucleoproteins, such as histone H3 at tyrosine 41 (H3Y41), nuclear factor 1-C2 (NF1-C2) and SWI/SNF-related helicases/ATPases (RUSH)-1α, indicating that JAK2 has a fresh nuclear function. Nuclear JAK2 is linked to a variety of cellular functions, such as cell cycle progression, apoptosis and genetic instability. The balance between these functions is an essential factor in determining whether a cell remains benign or becomes malignant. The aim of this review is intended to summarize the state of our knowledge on nuclear localization of JAK2 and nuclear JAK2 pathways, and to highlight the emerging roles for nuclear JAK2 in carcinogenesis.

Curcumin reverses chemoresistance of human gastric cancer cells by downregulating the NF-κB transcription factor.

Gastric cancer remains one of the major health problems worldwide. Chemotherapy is an important therapeutic modality for gastric cancer, but the success rate of this treatment is limited because of chemoresistance. The ubiquitously expressed transcription factor NF-κB has been suggested to be associated with chemoresistance of gastric cancer. Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance to chemotherapeutics are needed for the treatment of gastric cancer. Curcumin, a component of turmeric, is one such agent that has been shown to suppress NF-κB and increase the efficacy of chemotherapy. In this study, we investigated whether curcumin can reverse chemoresistance by downregulating NF-κB in human gastric cancer cells. SGC-7901 human gastric cancer cells was treated with chemotherapeutics (etoposide and doxorubicin) or by combined application of curcumin and chemotherapeutics. The viability of SGC-7901 cells was measured by MTT assay. Apoptosis of SGC-7901 cells was detected using the TUNEL and Annexin V/PI methods. The protein levels of NF-κB were analyzed by immunocytochemical staining. EMSA was used to confirm the increased nuclear translocation of RelA. The protein levels of p-IκBα, Bcl-2 and Bcl-xL were analyzed by Western blotting. The chemotherapeutics (etoposide and doxorubicin) suppressed the growth of SGC-7901 cells, in a time-dose-dependent manner. Use of curcumin in addition to these agents can suppress cell growth further (inhibitory rate: doxorubicin vs. doxorubicin + curcumin, 33% vs. 45%, p<0.05; etoposide vs. etoposide + curcumin, 35% vs. 48%, p<0.05). Furthermore, chemotherapeutics induced apoptosis of SGC-7901 cells and activated NF-κB. The combination of curcumin and chemotherapeutics induced apoptosis of SGC-7901 cells further, attenuated the activation of NF-κB, and reduced expression of the NF-κB-regulated anti-apoptotic gene products Bcl-2 and Bcl-xL. Curcumin potentiates the antitumor effects of chemotherapeutics in gastric cancer by suppressing NF-κB and NF-κB-regulated anti-apoptotic genes.

[Small interfering RNA inhibits cell proliferation in gastric cancer cell lines highly expressing RegIα].

OBJECTIVE: To investigate the effect of small interfering RNA on cell proliferation and apoptosis in gastric cancer cell lines with high expression of RegIα. METHODS: Total RNA was isolated from six gastric cancer cell lines,and the expression of RegI α mRNA was detected by RT-PCR. RegI α RNAi expression vector was constructed and stably transfected into MKN45 and AGS cells with high RegI α expression, empty-vector was used as control. RegI α mRNA and protein expression was measured by RT-PCR and Western blot respectively in stable transfected cell lines. Cell proliferation and apoptosis were detected with MTT assay and flow cytometry. RESULT: RT-PCR results indicated that RegI α mRNA expression was significantly inhibited by RNAi in both cell lines compared with empty-vector. Western blot results showed that RegIα protein was down-regulated to (44 ± 4)% and (25 ± 4)% respectively in MKN45 and AGS cells compared to empty-vector. MTT results showed that cell growth was significantly inhibited in MKN45 and AGS cells. The apoptosis rate in MKN45 and AGS cells was remarkable increased compared to that of empty-vector (12.96 ± 0.50)% compared with (3.99 ± 0.30)% and (11.59 ± 1.10)% compared with (4.22 ± 0.40)% (P < 0.05). CONCLUSION: Small interfering RNA of RegI α gene can efficiently down-regulate RegI α expression in MKN45 and AGS cell lines, and further inhibit cell growth and induce cell apoptosis.

[Construction of RegIα over-expression vector and its effect on proliferation and apoptosis of gastric cancer cells].

OBJECTIVE: To construct RegIα over-expression vector and to evaluate the effect of RegIα on the proliferation and apoptosis of gastric cancer MKN28 cells in vitro. METHODS: Full sequence of RegIα cDNA was amplified from normal gastric tissue samples by RT-PCR and cloned into pIRES2-EGFP vector. RT-PCR and Western blot were performed to detect expression levels of RegIα in MKN28 cells. The effects of over-expression RegIα on cell proliferation was measured by MTT assay and apoptosis was detected by flow cytometry. RESULT: RegIα cDNA over-expression vector of pIRES2-RegIα-EGFP was successfully constructed. The expressions of RegIα in MKN28 cells, including mRNA and protein levels, were significantly increased after stable transfection, which resulted in cell proliferation and anti-apoptotic effect induced by H(2)O(2). CONCLUSION: The over-expression of RegIα can promote cell proliferation and reduce cell apoptosis when induced by H(2)O(2) in gastric cancer cells.