Identification of non-invasive biomarkers for chronic atrophic gastritis from serum exosomal microRNAs.

BACKGROUND: Serum exosomal microRNAs (miRNAs) have been suggested as novel biomarkers for various diseases, especially gastric cancer (GC). But circulating biomarkers for Chronic atrophic gastritis (CAG) which is defined as precancrerous lesions of GC remain largely elusive. To investigate serum exosomal miRNAs that are differently expressed in CAG patients and Chronic nonatrophic gastritis (CNAG) may be helpful for its diagnosis and therapy. METHODS: Patients were recruited according to the diagnosis and exclusioncriteria. RNA was extracted from serum exosomes of 30 CAG and 30 CNAG patients. The miRNA expression profiles were analyzed by next generation sequencing and were validated by qRT-PCR. Receiver operating characteristic (ROC) analysis has been used to evaluate the diagnostic value. RESULTS: 30 CAG patients and 30 CNAG patients were recruited in our study. sRNA-seq results showed that hsa-miR-3591-3p, - 122-3p, and - 122-5p of the top 10 miRNAs (hsa-miR-148a-3p, - 122-3p, - 486-3p, -451a, - 122-5p, - 3591-3p, - 486-5p, -151a-3p, -92a-3p, -320a) were significantly upregulated in exosomes from CAG patients versus those from CNAG patients, but hsa-miR-451a, -151a-3p, and -92a-3p were significantly downregulated. Furthermore, qRT-PCR analysis confirmed that hsa-miR-122-5p and hsa-miR-122-3p were significantly upregulated in CAG samples, but hsa-miR-122-3p hadnot a steable expression. ROC curves showed that the AUC for hsa-miR-122-5p was 0.67 (95% CI 0.52-0.82, SE 62%, SP 86%). A sum of the four miRNAs (panel 1, hsa-miR-122-5p, -451a, -151a-3p, and -92a-3p) did not significantly improve the diagnostic potential (AUC 0.63, 95% CI 0.47 to 0.78). Correlation analysis showed that the expression of hsa-miR-122-5p differed significantly between patients based on atrophic (Moderate atrophic vs. Absent, P value was 0.036.) and IM (compare moderate-severe, absent and mild P values were 0.001 and 0.014, respectively). However, there were no differences between groups based on age, gender, dysplasia, or chronic or active inflammation. CONCLUSION: These results suggested that hsa-miR-122-5p in serum exosomes might serve as a potential biomarker for CAG diagnosis. TRIAL REGISTRATION: Chinese Clinical Trial Registy ( ChiCTR-IOR-16008027 , Date of Registration:2016-03-01).

Anti-inflammatory effect of Chang-An-Shuan on TNBS-induced experimental colitis in rats.

BACKGROUND: Inflammatory bowel disease (IBD), denominated by Crohn's disease and ulcerative colitis, is often associated with abdominal pain, diarrhea and bloody stool. The standard protocols for treating colitis conditions are not satisfactory; thus, complementary and alternative medicines have been increasingly accepted by IBD sufferers worldwide. In this study, we aimed to elucidate the anti-inflammatory effect of Chang-An-Shuan (CAS), a 6-herb Chinese medicinal formula, on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats and the underlying mechanisms. METHODS: Sprague-Dawley rats were administered with rectal gavage of 2.5% TNBS in 50% ethanol for the induction of experimental colitis which is considered as a model for Crohn's disease. Upon the TNBS induction, rats were given CAS at 0.5 g/kg/day or 5 g/kg/day for 10 days. The application of salicylazosulfapyridine (0.5 g/kg/day) was served as a positive reference drug for the colitis condition. The efficacy and mechanistic action of CAS were evaluated by means of histopathological and biochemical approaches such as histological staining, real-time polymerase chain reaction, Western blotting analysis and enzyme-linked immunosorbent assay. RESULTS: Oral administration of CAS at 5 g/kg/day, but not 0.5 g/kg/day, significantly ameliorated the severity of TNBS-induced colitis as evidenced by the reduced loss of body weight, alleviated diarrhea and decreased bloody stool. While lowering the disease activity index, the administration of CAS lessened mucosal lesions thus mucosal integrity of the colitis rats was notably improved. Further, the CAS treatment also significantly suppressed the mRNA and protein levels of pro-inflammatory cytokines, namely interleukin-1ß and tumor necrosis factor-α while enhancing the level of anti-inflammatory cytokine IL-10 in the TNBS-treated rats. Importantly, the ameliorative effect of CAS was related to an inhibition of the nuclear factor-κB (NF-κB) signaling pathway by downregulating the expression levels of NF-κBp-65, p-38 and p-AKT. CONCLUSIONS: We suggest that CAS is a potential alternative remedial approach for treating IBD conditions, and the anti-inflammatory effect of CAS is associated with the down-regulation of the NF-κB signaling pathway and the balanced production of pro- and anti-inflammatory cytokines.

[Mining analysis and experience summary for chronic atrophic gastritis cases treated by Professor LIU Feng-bin].

To summarize Professor LIU Feng-bin's clinical experience and theoretical thoughts on chronic atrophic gastritis (CAG), the study group designed a retrospective study on his case series and expert interview. First of all, the data of CAG patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine between 2009 and 2013, e. g. herbs, diseases, syndrome type, prescription amount and number of herbs, was collected and processed. The statistical description and binary logistic regression were used to determined the syndrome type, initial basic remedy and modification. During the statistics, a complete and sub-group analysis was performed simultaneously. After the expert interview, the syndrome type and medication were finalized. As a result, a total of 228 CAG patients aged at (50.30 ± 10.18) were collected, including 151 males (66.23%). Of them, the TCM diagnosis and syndrome type were extracted from the information of 157 patients, including 115 cases with gastric stuffiness, 23 cases with gastric pain, 19 missing cases, 2 cases with spleen-stomach weakness syndrome, 57 cases with spleen deficiency and dampness-heat syndrome, 18 cases with spleen-stomach disharmony syndrome, 23 cases with syndrome of liver depression syndrome, 21 cases with liver qi invading stomach syndrome and 26 qi and yin deficiency syndrome, respectively. All of the 228 patients used totally 104 herbs, while the subgroups with 157 patients used 94 herbs. The most frequently used 15 herbs used in each groups were analyzed to determine the initial basic remedy and modification. Subsequently, based on the information of the sub-groups with 157 patients, with the syndrome type as the dependent variable, the logistic regression analysis was made on the most frequently used 32 herbs, in order to determined the modification in herbs for different syndrome types. After experts reviewed and modified, they believed the main causes of CAG were dietary irregularities, moodiness and weak constitution; the pathogenesis of CAG was spleen deficiency with qi stagnation, heat depression and blood stasis in the stomach meridian. The above six syndrome types and 12 herbs were determined, including Pseudostellariae Radix, Poria, Atractylodismacrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Fritillariae Thunbergii Bulbus, Sepiae Endoconcha, Arecae Pericarpium, Aurantii Fructus, Perillae Caulis, Herba Hedyotis Diffusae, Scutellariae Barbatae Herba, Curcumae Rhizoma. This study summarized Professor LIU Feng-bin's clinical experience and theoretical thoughts of chronic atrophic gastritis based on clinical practice data and expert interview, with a rigorous design and good scientificity and practicability.

[General integral medicine: the strategic direction for complex health interventions].

Nowadays, the simple combination of Western medicine (WM) and complementary and alternative medicine (CAM) cannot resolve all the health problems and various requirements. This article proposed the general integral medicine (GIM) theoretical model, which declares the disease causes analysis, clinical intervention and outcomes assessment should be recognized, managed and evaluated both from physiological, psychological, and spiritual status, and all the four dimensions: orthodox medicine (WM, Chinese medicine, etc.), individual inherent characteristics (emotion, attitude, psychology, etc.), cultural influences (doctors, caregivers, groups care, etc.), and natural environment and social systems (economic status, social security system, environmental pollution, etc). As for health outcomes assessment, a more comprehensive system including biological, doctors, patients, health intimate, social and environmental evaluations were required. The GIM model has individualized, dynamic, standardized, objective, systematic inherent characteristics, and opening and compatible external characteristics. It aims to provide the new theoretical guidance and strategic development direction for complex health interventions, and solve various medical related psychological and social problems.

Oxcarbazepine versus Carbamazepine for the Treatment of Post-Stroke Epilepsy: A Systematic Review and Meta-Analysis.

AIM: To systematically evaluate the medication safety and effectiveness of Oxcarbazepine (OXC) and carbamazepine (CBZ) for the treatment of post-stroke epilepsy (PSE). MATERIAL AND METHODS: We searched Medline and other databases to identify the randomized controlled trials (RCTs) that compare the efficacies of OXC and CBZ in treating PSE. Two authors extracted and analyzed the data independently with Revman 5.3 software. The Q-test and I2 were used to test the statistical heterogeneity. The fixed or random effect models were selected according to heterogeneity. RESULTS: Eight RCTs that include 671 patients were involved in this study. The meta-analyses result showed that the overall efficiency of OXC was significantly better than that of CBZ (OR=4.55, 95% confidence interval (CI) (3.04?6.81)), the overall adverse events (OR=0.27, 95% CI (0.18?0.42), and the incidence of vomiting (OR=0.28, 95% CI (0.09?0.85)) of OXC was significantly less than that of CBZ. No significant differences in the incidence of rash (OR=0.45, 95% CI (0.19?1.07)), lethargy (OR=0.49, 95% CI (0.16?1.45)), and dizziness (OR=0.51, 95% CI (0.20?1.35)) were detected between OXC and CBZ. CONCLUSION: OXC seems to be superior to CBZ in the treatment of PSE, with higher efficacy, and safety than the latter. However, more research on OXC and CBZ in the treatment of PSE is required in the later stage due to the sample size limitation of our study.

Efficacy of traditional Chinese Medicine for gastric precancerous lesion: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate efficacy of traditional Chinese medicine (TCM) for gastric precancerous lesion (GPL). METHOD: Literature retrieval was conducted in seven databases from their inception through Dec. 24th, 2018. The Cochrane collaboration, Review Manager (RevMan5.3) and GRADE profiler software were conducted for this meta-analysis. RESULTS: In primary outcomes, results of meta-analysis showed that TCM had superior to current routine pharmacotherapy (RP) in clinical efficacy, Helicobacter pylori (Hp) eradication rate, efficacy under endoscopy, and TCM syndrome efficacy. Meanwhile, no potential publication bias was detected by Begg's and Egger's tests. In secondary outcomes, compared with control groups, experimental groups were more positive effects on improvement of stomach distention, stomachache, and heartburn. CONCLUSION: Our findings indicated that TCM could have positive effects on GPL. However, further standardized RCTs of rigorous design should be required to obtain more forceful evidence.

Long Noncoding RNA AFAP1-AS1 Promotes Cell Proliferation and Metastasis via the miR-155-5p/FGF7 Axis and Predicts Poor Prognosis in Gastric Cancer.

BACKGROUND: Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) plays an important role in the development and progression of several human cancers. However, its biological function in gastric cancer (GC) progression is still unknown. METHODS: We used qRT-PCR to detect the relative expression of AFAP1-AS1 in GC tissues and cell lines. The loss-of-function assays were conducted to detect the effect of AFAP1-AS1 on GC development. Bioinformatics analysis, luciferase reporter gene analysis, and RIP analysis were used to identify and validate target genes of AFAP1-AS1. Finally, rescue tests were performed to confirm the influence of the AFAP1-AS1-miR-155-5p-FGF7 axis on GC development. RESULTS: AFAP1-AS1 was upregulated in GC tissues and cell lines and was closely correlated with poor prognosis of GC patients. AFAP1-AS1 knockdown inhibited proliferation, migration, and invasion of GC cells, indicating that AFAP1-AS1 acts as an oncogene in GC. Bioinformatics analysis, dual-luciferase reporter gene detection, and RIP assays validated that AFAP1-AS1 directly interacts to miR-155-5p and could positively affect cell proliferation, migration, and invasion by regulation of the expression of miR-155-5p and FGF7. Further rescue assays revealed that AFAP1-AS1 promotes cell proliferation and metastasis through the miR-155-5p/FGF7 axis in GC. CONCLUSIONS: AFAP1-AS1 might be an oncogenic lncRNA that promoted GC progression by acting as a competing endogenous RNA (ceRNA) that regulates the expression of FGF7 through sponging miR-155-5p, suggesting that AFAP1-AS1 may be a novel potential therapeutic target for GC.

Musashi 1-positive cells derived from mouse embryonic stem cells treated with LY294002 are prone to differentiate into intestinal epithelial-like tissues.

The majority of Musashi 1 (Msi1)­positive cells derived from mouse embryonic stem cells (mESCs) are prone to differentiate into neural epithelial­like cells, and only a small proportion of Msi1­positive cells differentiate into intestinal epithelial­like cells. Whether inhibiting the phosphatidylinositol 3­kinase (PI3K) signaling of mESCs can promote the differentiation of Msi1­positive cells into intestinal epithelial­like cells remains to be fully elucidated. In the present study, to inhibit PI3K signaling, mESCs were treated with LY294002. A pMsi1­green fluorescence protein reporter plasmid was used to sort the Msi1­positive cells from mESCs treated and untreated with LY294002 (5 µmol/l). The Msi1­positive cells were hypodermically engrafted into the backs of non­obese diabetic/severe combined immunodeficient mice. The presence of neural and intestinal epithelial­like cells in the grafts was detected by reverse transcription­quantitative polymerase chain reaction analysis and immunohistochemistry. Compared with the Msi1­positive cells derived from mESCs without LY294002 treatment, Msi1­positive cells derived from mESCs treated with LY294002 expressed higher levels of leucine­rich repeat­containing G­protein coupled receptor, a marker of intestinal epithelial stem cells, and lower levels of Nestin, a marker of neural epithelial stem cells. The grafts from Msi1­positive cells treated with LY294002 contained more intestinal epithelial­like tissues and fewer neural epithelial­like tissues, compared with those from untreated Msi1­positive cells. LY294002 had the ability to promote the differentiation of mESCs into intestinal epithelial­like tissues. The Msi1­positive cells selected from the cell population derived from mESCs treated with LY294002 exhibited more characteristics of intestinal epithelial stem cells than those from the untreated group.

Expansion and activation of monocytic-myeloid-derived suppressor cell via STAT3/arginase-I signaling in patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. The dysregulated immune system plays an important role in the pathogenesis of AS. Myeloid-derived suppressor cells (MDSCs) play a key immunoregulatory role in autoimmune arthritis. The aim of this study was to clarify the underlying immunoregulatory mechanism of MDSCs in patients with AS. METHODS: Flow cytometry was used to analyze the phenotype of MDSCs among peripheral blood mononuclear cells (PBMCs) from 46 patients with AS and 46 healthy control subjects. The correlation between MDSC frequency and the disease index of patients with AS was evaluated. A T cell proliferation experiment was used to evaluate the immunosuppressive function of MDSCs. RESULTS: Polymorphonuclear (PMN) and monocytic (M)-MDSCs were significantly elevated in the PBMCs of patients with AS, when compared with levels in healthy controls. Additionally, M-MDSC levels correlated positively with the clinical index of AS, including the Bath ankylosing spondylitis disease activity index (BASDAI) score, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. M-MDSCs derived from patients with AS suppressed T cell responses, and this effect was dependent on the induction of arginase-I. Furthermore, AS-derived M-MDSCs showed high levels of phosphorylated STAT3. Stattic, a STAT3-specific inhibitor, and STAT3-targeted siRNA abrogated the immunosuppressive function of M-MDSCs. Inhibition of STAT3 signaling also resulted in decreased arginase-I activity. CONCLUSIONS: STAT3/arginase-I signaling plays an important role in both the expansion and activation of M-MDSCs in patients with AS. This information may be beneficial in developing novel therapeutic strategies for preventing AS.

Changes of cytoskeleton and cell cycle in Lovo cells via deletion of Rac1.

BACKGROUND: Rac1, the better characterized Rac subfamily member, can regulate a large variety of different functions, including the organization of the actin cytoskeleton, cell migration, cell cycle progression, and cell survival through engagement of specific effectors. However, very little is currently known about the expression of Rac1 in colorectal cancer cells and the roles of Rac1 in the cell cycle progression and cell survival of human colorectal cancer cells. OBJECTIVE: To assess the change of cytoskeleton and cell cycle in Lovo (human colorectal cancer) cell via deletion of Rac1 with RNA interference. METHODS: Rac1 protein of all selected human colorectal cancer cells and in human colorectal tissue was detected by Western blotting, Rac1-shRNA was used to silence the Rac1 to reduce its expression specifically in Lovo cells. RESULTS: Rac1 protein was overexpressed in human colorectal cancer cells and in human colorectal tissue, RNA interference-mediated deletion of Rac1 strongly prolonged cell cycle progression and enhanced cell apoptosis of Lovo cells in vitro. CONCLUSIONS: depletion of Rac1 by the use of RNAi can arrest Lovo Cells in G_{0}/G_{1} and induce LoVo cells apoptosis.

Effect of ozone on aflatoxins detoxification and nutritional quality of peanuts.

Aflatoxins are a group of secondary metabolites produced by Aspergillus flavus and Aspergillus parasiticus with carcinogenicity, teratogenicity, and mutagenicity. Aflatoxins may be found in a wide range of agri-products, especially in grains, oilseeds, corns, and peanuts. In this study, the conditions for detoxifying peanuts by ozonation were optimised. Aflatoxins in peanuts at moisture content of 5% (w/w) were sensitive to ozone and easily degraded when reacted with 6.0mg/l of ozone for 30min at room temperature. The detoxification rates of the total aflatoxins and aflatoxin B1 (AFB1) were 65.8% and 65.9%, respectively. The quality of peanut samples was also evaluated in this research. No significant differences (P>0.05) were found in the polyphenols, resveratrol, acid value (AV), and peroxide value (PV) between treated and untreated samples. The results suggested that ozonation was a promising method for aflatoxin detoxification in peanuts.

Protective effects of BML-111 on cerulein-induced acute pancreatitis-associated lung injury via activation of Nrf2/ARE signaling pathway.

The aim of this study was to investigate whether BML-111 can exert protective effects on cerulein-induced acute pancreatitis-associated lung injury (APALI) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) signaling pathway. Severe acute pancreatitis (SAP) was established by intraperitoneal injection of cerulein (50 µg/kg) seven times at hourly intervals and Escherichia coli lipopolysaccharide (10 mg/kg) once after the last dose of cerulein immediately. BML-111 (1 mg/kg) was administered 1 h before the first injection of cerulein. Samples were taken at 3, 6, 12, and 24 h after the last injection. Pathologic lesions of the pancreas and lung tissues as well as the levels of serum amylase were analyzed; Myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase-1 (NQO1) of lung tissue were determined. The findings revealed that the injuries of pancreas and lung were typically induced by cerulein. The administration of BML-111 reduced the levels of serum amylase, lung MPO, lung MDA, the wet-to-dry weight ratio, and the pathology injury scores of the lung and pancreas, which increased in the SAP group. The expressions of Nrf2, HO-1, NQO1, and activity of SOD in lung tissue increased in the BML-111 group compared with those in the SAP group. This study indicates that BML-111 may play a critical protective role in APALI induced by cerulein. The underlying mechanisms of protective role may be attributable to its antioxidant effects through the activation of Nrf2/ARE pathway.

Literature review and analysis of the application of health outcome assessment instruments in Chinese medicine.

OBJECTIVE: To evaluate the application of health assessment instruments in Chinese medicine. METHODS: According to a pre-defined search strategy, a comprehensive literature search for all articles published in China National Knowledge Infrastructure databases was conducted. The resulting articles that met the defined inclusion and exclusion criteria were used for analysis. RESULTS: A total of 97 instruments for health outcome assessment in Chinese medicine have been used in fundamental and theoretical research, and 14 of these were also used in 29 clinical trials that were randomized controlled trials, or descriptive or cross-sectional studies. In 2 152 Chinese medicine-based studies that used instruments in their methodology, more than 150 questionnaires were identified. Among the identified questionnaires, 51 were used in more than 10 articles (0.5%). Most of these instruments were developed in Western countries and few studies (4%) used the instrument as the primary evidence for their conclusions. CONCLUSION: Usage of instruments for health outcome assessment in Chinese medicine is increasing rapidly; however, current limitations include selection rationale, result interpretation and standardization, which must be addressed accordingly.

Microsensor in vivo monitoring of oxidative burst in oilseed rape (Brassica napus L.) leaves infected by Sclerotinia sclerotiorum.

Oxidative burst is the rapid and transient production of large amounts of reactive oxygen species, including superoxide anion, hydrogen peroxide (H(2)O(2)), and hydroxyl radical. A rapid and simple technique was employed for in vivo detection of oxidative burst in oilseed rape (Brassica napus L.) leaves, using a modified electrode. Platinum (Pt) micro-particles were dispersed on a Pt electrode, coated with a poly (o-phenylenediamine) film. This exhibited high sensitivity, selectivity and stability in H(2)O(2) detection. Amperometry was used to obtain satisfactory linear relationships between reductive current intensities and H(2)O(2) concentrations at -0.1 V potential in different electrolytes. This electrode was used in vivo to detect oxidative burst in oilseed rape following fungal infection. Oxidative bursts induced by infection of the fungal pathogen Sclerotinia sclerotiorum (Lib.) de Bary exhibited notably different mechanisms between a susceptible and a resistant glucose oxidase-transgenic genotype.