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.
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-HT
receptor antagonist NAN-190 hydrobromide (NAN-190) prevented such effects. While sub-threshold of 5-HT
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-HT
-dependent PKA-CREB-BDNF signaling in the brain-gut axis.
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.
By improving retinoic acid synthesis, a novel probiotic L. intestinalis exerts a protective effect against colitis. Retinoic acid triggers epithelial gene alteration, including SAA1, SAA2, and C/EBPA, to downregulate RORγt+ Th17 cells. L. intestinalis and its associated metabolite, retinoic acid, have potential therapeutic effects for suppressing colonic inflammation.
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
-Resveratrol affects chronic-acute combined stress (CACS)-induced IBS-like symptoms including depression, anxiety and intestinal dysfunction.
ICR male mice were exposed to the CACS for 3 weeks.
-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
-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.
Administration with
-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
-Resveratrol in treatment of IBS-like disorder. Furthermore,
-Resveratrol improved hippocampal neuronal remodeling, protected ileal and colonic epithelial barrier structure against CACS insults. The further study suggested that
-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
-Resveratrol.
The dual effects of
-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.
It has been noticed that gastroenteritis or dysentery plays a role in pathogenesis of irritable bowel syndrome (IBS), and antibiotics can increase functional abdominal symptoms, both of which may be ...partly due to intestinal flora disorders. This study was to determine the change of gut flora of IBS, a cluster of abdominal symptoms. Because of the chronic course and frequent occurrence of the disease, IBS patients suffered much from it. So the quality of life (Qol) of IBS patients was also evaluated in this study.
Twenty-five Rome II criteria-positive IBS patients were recruited, and 25 age and gender-matched healthy volunteers were accepted as control. The fecal flora, including Lactobacillus, Bifidobacterium, Bacteroides, C. perfringens Enterobacteriacea and Enterococus, were analyzed quantitatively and qualitatively. We also calculated the ratio of Bifidobacterium to Enterobacteriaceae (B/E ratio) in both IBS patients and controls. In both groups, the data were further analyzed based on age difference, and comparisons were made between the younger and elder subgroups. We also evaluated the quality of life (QoL) of IBS patients and the control group using the Chinese version of SF-36 health questionnaire.
In IBS patients, the number of fecal Bifidobacterium was significantly decreased and that of Enterobacteriaceae was significantly increased compared with that in healthy controls (both P<0.05). The mean microbial colonization resistance (CR) of the bowel in IBS patients was smaller than 1, making a significant difference compared with that in control which was more than 1 (P<0.01). There was no significant difference in gut flora between two subgroups. While in control, the elder subgroup presented more Enterobacteriacea than the younger one (P<0.05). Compared with the control group, IBS patients had significantly lower scores on all SF-36 scales, with the exception of physical functioning. However, there was no significant correlation between quality of life and enteric symptoms in IBS patients.
There are intestinal flora disorders in IBS patients, which may be involved in triggering the IBS-like symptoms. IBS patients experience significant impairment in QoL, however, the impairment is not caused directly by enteric symptoms.
@Yun Qian$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang ...University!Hangzhou 310016, Zhejiang Province, China@Chi-Chun Wong$Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong!Hong Kong, China@San-Chuan Lai$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Zheng-Hua Lin$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Wei-Liang Zheng$Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Hui Zhao$Emergency Department, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Kong-Han Pan$Department of Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Shu-Jie Chen$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Jian-Min Si$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China
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.
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.
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.
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.
•An innovative strategy for recycling waste concrete is proposed.•Mass ratio of total waste content in recycled lump/aggregate concrete is great.•Good strength can still be attained when mass ratio ...of total waste content is 55%.•Formula is proposed to predict elastic modulus of recycled lump/aggregate concrete.•Recycled aggragate concrete with 100% replacement ratio is not suggested to be used.
Reusing coarsely crushed demolished concrete lumps (DCLs) and recycled coarse aggregates (RAs) simultaneously is proposed as a way to improve the total waste content in concrete. The compressive behaviour of compound concrete containing DCLs and recycled aggregate concrete (RAC), which referred to as recycled lump/aggregate concrete (RLAC), was experimentally investigated. In addition, mercury intrusion porosimetry and scanning electron microscope were employed to investigate the interfacial transition zone between DCLs and RAC at the micro level. The results revealed that: (a) the total waste content in RLAC can reach more than twice that in RAC in engineering practice; (b) when the compressive strength of RAC stays almost unchanged, only the compressive strength of RLAC containing RAC with 100% RA replacement ratio is relatively much lower; (c) satisfactory compressive strength can still be attained even when the total waste content in RLAC reaches 54.6%; and (d) when the RA replacement ratio is 100%, the porosity and harmful pores in the fresh mortar surrounding DCLs increase remarkably.
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 pmol/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.
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