BACKGROUND:Gastric cancer (GC) is a widespread malignancy and associated with high rates of morbidity and mortality worldwide. AIM:To examine the functional role of long non-coding RNAs small nucleolar RNA host gene 5 (SNHG5) and its regulation of miR-92a-3p and B-cell translocation gene 2 (BTG2) in GC progression. METHODS:Quantitative reverse transcription PCR and western blot analysis determined the expression of SNHG5, miR-92a-3p, and BTG2 in GC and adjacent non-neoplastic mucosa. Dual-luciferase assays demonstrated interactions of SNHG5 with miR-92a-3p and BTG2. AGS cells were transfected with SNHG5 overexpression and miR-92a-3p knockdown models. Various assays, including CCK-8, colony formation, scratch wound healing, and Transwell assays, were used to determine cell proliferation and migration. An experimental model of a xenograft mouse was used to determine in vivo tumor growth. At the same time histological changes were evaluated by hematoxylin and eosin staining, with western blot analysis used to evaluate signaling pathway protein expression. RESULTS:BTG2 and SNHG5 were downregulated in GC tissues, and miR-92a-3p was upregulated. Overexpression of SNHG5 or knockdown of miR-92a-3p reduced GC cell proliferation and migration, and increased BTG2 expression while decreasing PI3K/AKT signaling activity. The dual-luciferase assays demonstrated direct binding of miR-92a-3p to SNHG5 and BTG2. Tumor volume and weight were significantly reduced in mice transplanted with AGS cells treated with miR-92a-3p inhibitor or SNHG5 overexpression compared with control AGS cells. Hematoxylin and eosin staining revealed that treated tumors exhibited degenerative characteristics, including irregular morphology and nucleolysis. CONCLUSION:LncRNA SNHG5 inhibited GC cell growth and migration by modulating the PI3K/AKT pathway via the miR-92a-3p/BTG2 axis.
Background/Aim: Chemotherapy based on 5-fluorouracil (5-Fu) is the first-line treatment for advanced gastric cancer (GC) patients. Importantly, 5-Fu resistance is recognized as a major obstacle for the successful treatment of GC. Circular RNAs (circRNAs) are non-coding RNAs involved in the pathogenesis of GC. However, their role in the mechanism of 5-Fu resistance in GC remains largely unknown. The purpose of this study was to explore and elucidate the biological function and molecular mechanism of circRNAs underlying 5-Fu resistance in GC. Materials and Methods: High-throughput sequencing results for intersection analysis were used to select a novel differentially expressed circRNA hsa_circ_0004650. The expression levels of the new circRNA between 5-Fu-sensitive and 5-Fu-resistant GC cells were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), and biological behaviors, such as proliferation and apoptosis of GC cells, were observed after silencing the hsa_circ_0004650. The mechanism of hsa_circ_0004650 sponges miR-145-5p to regulate 5-Fu resistance in GC cells was investigated by luciferase reporter assay, qRT-PCR, CCK-8 assay, Calcein AM/PI double fluorescence staining and flow cytometry. Results: hsa_circ_0004650 was identified as a differentially expressed circRNA between 5-Fu-sensitive GC and 5-Fu-resistant GC cells. Hsa_circ_0004650 was up-regulated in 5-Fu-resistant GC cells. Silencing of hsa_circ_0004650 in 5-Fu-resistant GC cells, the survival rates of cells treated with increasing doses of 5-Fu for 24 h and 48 h were decreased (p<0.01); the mortality rates of SGC-7901-5-Fu cells were increased (17.86%+/- 0.6 vs. 44.86%+/- 1.52; p<0.001), and those of BGC-823-5-Fu cells were increased (8.17%+/- 7.80 vs. 26.61%+/- 1.12; p<0.001); and the apoptosis rates of cells treated with the same concentration of 5-Fu were increased (p<0.001). Mechanistically, miR-145-5p was confirmed as a downstream target of hsa_circ_0004650. By the down-regulation of the expression of miR-145-5p in 5-Fu-resistant GC cells, the survival rates of cells treated with increasing doses of 5-Fu for 24 h and 48 h were increased (p<0.05); the mortality rates of SGC-7901-5-Fu cells were decreased (12.86%+/- 1.10 vs. 7.83%+/- 0.53; p<0.01), those of BGC-823-5-Fu cells were decreased as well (16.99%+/- 1.31 vs. 11.40%+/- 0.72; p<0.01); and the apoptosis rates of cells treated with the same concentration of 5-Fu were decreased (p<0.001). Conclusion: The circRNA hsa_circ_0004650 promotes chemotherapy resistance to 5-Fu in GC cells through sponge adsorption of miR-145-5p, which offers a potential approach to overcome 5-Fu resistance in GC.
Background:Whether circRAN, which acts as a microRNA sponge, plays a role in 5-fluorouracil (5-Fu) resistant gastric cancer has not been reported. In this study, a 5-Fu resistant cell line with an IC50 of 16.59 µM was constructed.Methods:Using comparative analysis of circRNA in the transcriptomics of resistant and sensitive strains, 31 differentially expressed circRNAs were detected, and the microRNA interacting with them was predicted.Results:Hsacirc_004413 was selected for verification in drug resistant and sensitive cells. By interfering with hsacirc_004413 using antisense RNA, the sensitivity of drug resistant cells to 5-Fu was significantly promoted, and the apoptosis and necrosis of the cells were significantly increased. In sensitive cells, inhibition by inhibitors enhanced the resistance of cells to 5-Fu. We hypothesize that hsacirc_004413 makes gastric cancer cells resistant to 5-Fu mainly through adsorption of miR-145-5p.
ABSTRACT:Ileocolonoscopy is currently recognized as the gold standard for evaluating mucosal healing in patients with Crohn disease (CD). However, the ideal noninvasive marker to assess mucosal healing instead of invasive ileocolonoscopy is not available. This study aimed to determine the correlations between the mucosal healing and serological optimizing markers in CD.This retrospective study consecutively included 62 CD patients with 137 hospitalizations between March 2014 and March 2020. On the basis of the Simple Endoscopic Score for Crohn's disease (SES-CD), the CD patients were divided into mucosal healing group (SES-CD ≤ 2) and nonmucosal healing group (SES-CD > 2). We collected the results of ileocolonoscopy examination and inflammatory markers and then serological optimizing markers, including C-reactive protein/albumin ratio (CRP/ALB), platelet/albumin ratio (PLT/ALB), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. The control group consisted of 50 healthy volunteers in the corresponding period.We found that CRP/ALB, PLT/ALB, NLR, and PLR were correlated with the mucosal healing of CD, and the correlation of CRP/ALB with the mucosal healing was the highest (r = -0.64). Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CRP/ALB (0.87) was higher than NLR (0.69), PLR (0.72), and PLT/ALB (0.81). In the efficacy of assessing the mucosal healing in CD, the sensitivity of CRP/ALB, NLR, PLR, and PLT/ALB were 91.1%, 83.9%, 73.2%, and 73.2%, respectively, and the specificity was 76.5%, 46.9%, 64.2%, and 75.3%, respectively.CRP/ALB was the most appropriate marker to assess CD mucosal healing among the serological optimizing markers.
Background Chronic active Epstein-Barr virus infection (CAEBV) is a rare disease, which is difficult to be differentiated from inflammatory bowel disease (IBD). To cause the attention, we present twelve cases of CAEBV in immunocompetent patients with gastrointestinal tract involvement. Methods Twelve patients who fulfilled the diagnostic criteria of CAEBV were enrolled in this retrospective study. The control group was consisted of twenty-four IBD patients with EBV-DNA value increased in peripheral blood. The clinicopathologic and endoscopic characteristics were reviewed and analyzed. Results The major clinical presentations of CAEBV patients were intermittent fever (100%), hepatomegaly/splenomegaly (58%), lymphadenopathy (50%), diarrhea (50%) and hematochezia (50%). Compared with IBD patients, the incidence of intermittent fever and increased level of ferritin were significantly higher among CAEBV patients. The median values for EBV detected in peripheral blood were significantly higher in CAEBV group (1.42*10^6 copies/μg) than in IBD group (3.2*10^3 copies/μg, p <0.05). The main endoscopic findings of CAEBV included multifocal or isolated, irregular, multiform ulcers and diffuse inflammation, lacking of typical cobblestone appearance. Ten patients died within 5 years of disease onset. The average survival time is 21 months. Conclusions Symptoms such as intermittent fever, increased level of ferritin and atypical endoscopic findings could be a sign for CAEBV. Early detections of EBV-DNA in serum and EBV-encoded small nuclear RNA (EBER) by in situ hybridization in intestinal tissue are essential for differential diagnosis between CAEBV and IBD.
Hematologic and neurological expression 1 (HN1) has been reported to involved in certain cancers, but its role in hepatocellular carcinoma (HCC) is largely unknown. The contribution of HN1 to HCC progression was investigated in the present study. We found that HN1 was significantly up-regulated in HCC tissues, compared with normal tissues, by analyzing the Oncomine and Human Protein Atlas database; and found that high expression of HN1 was markedly associated with worse overall survival, relapse-free survival, progression- free survival and disease-specific survival in HCC patients via exploring the Kaplan-Meier plotter database. Functional assays revealed that HN1 knockdown by siRNA induced G1 cell cycle arrest, and inhibited the growth and migration of HCC cells; accordingly, HN1 over-expression promoted HCC cells proliferation and migration. Further studies indicated that HN1 knockdown reduced the expression of cyclin D1 and CDK4, while upregulated the cell cycle inhibitor p21WAF1/Cip1. Moreover, HN1 knockdown decreased c-Met (receptor tyrosine kinase of hepatocyte growth factor) expression, and suppressed ERK activation, which is a common downstream signaling pathway triggered by c-Met; consistently, HN1 over-expression reversed these effects. Meanwhile, down-regulation of c-Met partly eliminated the effect of HN1 over-expression in HCC cells. Thus, the present findings suggested that HN1 promotes the progression of HCC to some extent by up-regulating the expression of c-Met, and may act as a potential biomarker and therapeutic target for the treatment of HCC.
In China, hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer and the leading cause of cancer death in men, followed by lung and stomach cancer. There was an urgent need to identify novel prognostic biomarkers for HCC. We explored the expression pattern of m6A related proteins in HCC tissues by using TCGA in this study. We found that the m6A 'reader' YTHDF1 was significantly upregulated in HCC and was positive correlated with pathology stage. Kaplan-Meier analysis showed that Lower YTHDF1 expression level was associated with better survival of HCC patients. Furthermore, we performed GO and KEGG pathway analysis of YTHDF1 co-expressed genes and found YTHDF1 played an important role in regulating HCC cell cycle progression and metabolism. We believed that this study will provide a potential new therapeutic and prognostic target for HCC.
Objective To evaluate the clinical value of Danshen polyphenolate injection in the treatment of ischemic colitis. Methods Thirty patients with ischemic colitis were enrolled and randomly divided into control group (n=10) and treatment group (n=20), who were in hospital from January 2017 to December 2018.The control group was treated conservatively, and the treatment group was treated with intravenous infusion of Danshen polyphenolate injection on the basis of the control group.After treatment, the clinical index, morphological indices and laboratory indicators of the two groups were compared, and the clinical efficacy was compared between the two groups. Results There was no significant difference in remission and hospitalization days between the treatment group and the control group (P> 0.05).The days of occult blood turning cloudy in the treatment group were earlier than those in the control group (P < 0.05).After treatment, there was no significant difference in the degree of inflammation and ischemia between the treatment group and the control group (P>0.05).There was statistical significance in necrosis between the treatment group and the control group (P < 0.05).The platelet function in the treatment group was significantly lower than that in the control group (P < 0.05).Before treatment, there was no significant difference in positive area and OD value between the treatment group and the control group (P> 0.05).After treatment, the positive area and OD value of the treatment group were significantly higher than those of the control group (P < 0.05).There was no significant difference in clinical efficacy between the two groups (P> 0.05), but the curative effect of the treatment group was better than that of the control group. Conclusion Conservative treatment combined with Danshen polyphenolate injection in the treatment of patients with ischemic colitis can effectively improve the clinical indicators, morphological indicators and laboratory indicators, and improve the overall therapeutic effect.
Objective To investigate the effect of early feeding on postoperative recovery of laparoscopic resection of colorectal cancer. Method A total of 118 patients who had undergone laparoscopic colorectal resection were enrolled and divided into early feeding group and conventional feeding group according to whether early postoperative feeding was adopted, with 59 cases in each team. The postoperative recovery, nutritional status and complications were observed and compared between the two groups. Results No significant difference was detected in prealbumin and albumin levels before surgery between the two groups (P>0.05). The postoperative levels of prealbumin and albumin in the two groups were improved, and the improvement of the early feeding group was significantly greater than that of the conventional feeding group (P<0.05). When Compared with conventional feeding group, in early feeding group, the first exhaust time and the first defecation time after surgery were short, the hospitalization expense was low, and the differences were statis-tically significant (P<0.05);There was no significant difference found in hospitalization time between the two groups (P>0.05). No serious complications were observed in both groups (P>0.05). Conclusion It is safe and effective for early feeding after laparoscopic resection of colorectal cancer, which can improve the postoperative nutritional status and lead to rapid recovery. It is worthy of wide application in clinical practice.
Objective To study the role of salvianolate in the treatment of inflammation of intestinal mucosa by colitis mice model.Methods A total of 60 C57BL/6J mice were divided into acute control group,acute model group,acute interventional group,chronic control group,chronic model group and chronic interventional group with 10 mice in each group.Dextran sodium sulfate
Cholestyramine (CHO), as a bile acid sequestering exchange resin, has been widely used to treat hypercholesterolemia. The aim of this study was to explore how CHO regulated serum cholesterol amounts and bile acid levels in animal models. New Zealand White rabbits were randomly assigned to the control (given distilled water) and CHO-treated (given CHO solution 1 g/kg per day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were constructed in five rabbits in each group. Serum cholesterol levels and biliary and fecal bile outputs were determined. Liver cholesterol 7α-hydroxylase ( CYP7A1 ), small heterodimer partner ( SHP ), bile salt export pump ( BSEP ), ileal bile acid-binding protein ( IBABP ) and LDL receptor ( LDL-R ) mRNA expressions were assessed by real-time polymerase chain reaction. CYP7A1 activity was also determined. CHO treatment decreased serum cholesterol levels by 12.1%. Although CHO did not change the bile acid pool size and biliary bile acid output, it significantly increased fecal bile acid output. Interestingly, CHO also significantly increased the expression and activity of CYP7A1, as well as IBABP and LDL-R mRNA expressions, but decreased hepatic SHP and BSEP gene expressions. CHO markedly alters bile acid and cholesterol amounts in rabbit intestinal and liver tissues, downregulating genes responsible for cholesterol homeostasis.
OBJECTIVECholestyramine (CHO), as a bile acid sequestering exchange resin, has been widely used to treat hypercholesterolemia. The aim of this study was to explore how CHO regulated serum cholesterol amounts and bile acid levels in animal models. METHODS New Zealand White rabbits were randomly assigned to the control (given distilled water) and CHO‐treated (given CHO solution 1 g/kg per day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were constructed in five rabbits in each group. Serum cholesterol levels and biliary and fecal bile outputs were determined. Liver cholesterol 7α‐hydroxylase ( CYP7A1 ), small heterodimer partner ( SHP ), bile salt export pump ( BSEP ), ileal bile acid‐binding protein ( IBABP ) and LDL receptor ( LDL‐R ) mRNA expressions were assessed by real‐time polymerase chain reaction. CYP7A1 activity was also determined. RESULTS CHO treatment decreased serum cholesterol levels by 12.1%. Although CHO did not change the bile acid pool size and biliary bile acid output, it significantly increased fecal bile acid output. Interestingly, CHO also significantly increased the expression and activity of CYP7A1, as well as IBABP and LDL‐R mRNA expressions, but decreased hepatic SHP and BSEP gene expressions. CONCLUSION CHO markedly alters bile acid and cholesterol amounts in rabbit intestinal and liver tissues, downregulating genes responsible for cholesterol homeostasis.
活性氧簇(ROS )是一类含氧的化学活性分子,是体内正常氧代谢的自然副产物,紫外线照射、感染等均可导致体内ROS过度生成,从而引起氧化应激损伤。炎症性肠病(IBD )是一种反复发作的慢性非特异性肠道炎性疾病,其病因和发病机制尚未明确,有研究表明肠道炎性反应与ROS等活性中间产物的过量产生密切相关,因此氧化应激亦被认为是IBD的病理生理学机制之一。
This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway.
Objective To observe the treatment effect of Salvianolic injection on the adipokines of mice with experi-mental colitis and investigate the possible mechanism of it .Methods Thirty BALB/C mice were randomly divided into control group, modle group and interventional group .Colitis was induced by 5%DSS oral administration for 7 d.14 d later, indices were determined .Results Treatment of mice with Salvianolic injection could reduce colon inflammation induced by DSS ( P<0 .01 ) .Serum chemerin , leptin were higher in the model group than those in the control group ( P<0.05), but adiponectin decreased (P<0.05).Leptin decreased in the interventional group (P<0.05), while the changes of chemerin and adiponectin had no statistically significance ( P>0 .05 ) .Conclusion Salvianolic injection have some theroputic effect on colitis in mice ,and the mechanism maybe due to its regulation effcet on adipokines .
Objective This paper investigated the clinical efficacy of escitalopram in treating functional gastrointestinal disorder patients with health anxiety .Methods 42 patients were divided into two groups ,the deanxit group and the other psychiatric drugs group (here after referred to as"the other group") ,according to their primary psychiatric medication .Their primary psychiatric medication was replaced with escitalopram and continued treating with primary gastrointestinal drugs as a combination therapy .Results A 90 .5% of efficacy and an 81 .0% of remission were obtained in the deanxit group ,while only an 80 .0% of efficacy and a 60% of remission were obtained in the other group .A total 85 .4% efficacy and 70 .7% of remission were obtained in all patients .Conclusion Escitalopram and gastrointestinal drugs used as a combination had high clinical efficacy in treating functional gastrointestinal disorder patients with health anxiety .
肠型白塞氏病较为罕见,与克罗恩病的鉴别较困难.因其治疗方法有所差异,临床工作中需注意鉴别诊断.
AIM:To observe whether Salvianolate Injection has a therapeutic effect on colitis and to discuss the possible mechanisms involved.METHODS:50 Balb/c mice were randomly divided into a control group,a model group,and low-,medium-,and high-dose interventional groups.Colitis was induced by oral administration of 5% DSS for 7 d.Indices were determined 14 d after colitis induction.RESULTS:Treatment with Salvianolate Injection could reduce colonic inflammation induced with DSS (P < 0.01).Immunohistochemistry analysis showed that treatment with different doses of Salvianolate Injection significantly reduced CD40/CD40L protein expression compared to the model group (CD40:20.50 μm2 ±1.517 μm2,15.50 μm2 ± 4.680 μm2,13.33 μm2 ±0.816 μm2 vs 30.33 μm2 ± 4.227 μm2,all P < 0.01;CD40L:23.17 μm2 ± 2.714 μm2,15.50 μr2 ± 2.739μm2,14.17 μm2 ± 4.262 μm2 vs 27.83 μm2 ± 3.710μm2,all P < 0.01).RT-PCR analysis showed that treatment with different doses of Salvianolate Injection significantly reduced CD40/CD40L mRNA expression compared to the model group (CD40:1.20% ± 0.30%,0.78% ± 0.26%,0.41% ±0.15% vs 1.78% ± 0.41%,all P < 0.01; CD40L:2.59%± 1.68%,1.75% ± 0.64%,1.11% ± 0.53% vs 3.54% ±0.85%,all P < 0.01).The concentration of sCD40L in medium was decreased in the medium-and high-dose interventional groups compared to the model group (2.12 ng/mL ± 0.18 ng/mL,1.96ng/mL ± 0.12 ng/mL vs 5.62 ng/mL ± 0.36 ng/mL,P < 0.01).CONCLUSION:Salvianolate Injection can exert a therapeutic effect on colitis in mice possibly by reducing sCD40L and thus restraining the CD40/CD40L pathway.
Anti-platelet drugs have been used to treat inflammatory bowel disease. In this study, we observed the therapeutic effects of magnesium lithospermate B, a main component of salvianolate, on colitis induced by dextran sodiumsulfate (DSS). Colitis was induced by 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (60-240mg/kg) was given by subcutaneous injection for 2 weeks. Then, mice were sacrificed; serum and colon tissues were collected for biomarker assay, histological examination, immunohistochemical study and real-time quantitative polymerase chain reaction. DSS induced gross bleeding, inflammation, crypt damage and mucosal damage in colon. Treatment with magnesium lithospermate B could reduce colon inflammation induced by DSS. Magnesium lithospermate B could reverse the high CD40/CD40L expression and hypercoagulable state induced by DSS in colon. This study showed that magnesium lithospermate B could be used to treat colitis. The protective effects of magnesium lithospermate B may be due to its effects on CD40/CD40L expression and blood clotting status.