Ethanol extract of Andrographis paniculata alleviates aluminum-induced neurotoxicity and cognitive impairment through regulating the p62-keap1-Nrf2 pathway.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative and remains incurable. Aluminum is a potent neurotoxin associated with AD. The main pathological features of AD are extracellular amyloid-ß protein deposition and intracellular hyperphosphorylated Tau protein. A body of evidence suggest that oxidative stress and autophagy are involved in the pathogenesis of AD. Andrographis paniculata (AP) is a native plant with anti-inflammatory, anti-oxidative stress, and regulation of autophagy properties. AP significantly alleviated cognitive impairments, reduced Aß deposition and has neuroprotective effect. However, its effects on aluminum-induced AD model have not been studied much. In this study, we investigated whether AP protect against aluminum-induced neurotoxicity through regulation of p62-Kelch-like ECH-associated protein 1(Keap1)-Nuclear factor E2 related factor 2 (Nrf2) pathway and activation autophagy in vivo and in vitro. METHODS: UPLC-ESI-qTOF-MS/MS was used to identify the chemical constituents of AP ethanol extract. The mice with cognitive deficit were established by injecting aluminum chloride and D-galactose, and treated with either AP extract (200, 400, or 600 mg/kg/d) or andrographolide (2 mg/kg/2d).The spatial memory ability was detected by Morris water maze, HE staining were used to detect in brain tissue,Oxidative stress indexs and SOD activity in both serum and brain tissue were detected by kit.The expression of p62-Nrf2 pathway proteins were measured via western blotting. Furthermore, the neurotoxicity model was induced by aluminum maltolate (700 µM) in PC12 cells. Following AP and andrographolide treatment, the cell viability was detected. The relevant mRNA and protein expressions were detected in cells transfected with the p62 siRNA. RESULTS: The main active components of AP included andrographolide, neoandrographolide and deoxyandrographolide as identified. AP and andrographolide significantly improved the spatial memory ability of mice, attenuated pathological changes of hippocampal cells, reduced the level of malondialdehyde, and increased superoxide dismutase activity in serum or brain tissue as compared to model control. In addition, the Nrf2, p62 and LC3B-II proteins expression were increased, and p-Tau and Keap1 proteins were decreased in the hippocampus after AP and andrographolide treatment.Furthermore, AP increased aluminum maltolate-induced cell viability in PC12 cells. Silencing p62 could reverse the upregulation expression of Nrf2 and downregulation of Keap1 and Tau proteins induced by AP in aluminum maltolate-treated cells. CONCLUSIONS: AP had neuroprotective effects against aluminum -induced cognitive dysfunction or cytotoxicity, which was involved in the activation of the p62-keap1-Nrf2 pathway and may develop as therapeutic drugs for the treatment of AD. However, this study has certain limitations, further optimize the protocol or model and study the molecular mechanism of AP improving AD.

Perioperative parenteral fish oil supplementation improves postoperative coagulation function and outcomes in patients undergoing colectomy for ulcerative colitis.

OBJECTIVE: Ulcerative colitis (UC) is an independent risk factor for thromboembolism, especially during the perioperative period. This study aimed to determine the effects of perioperative parenteral nutrition (PN) supplemented with fish oil (FO) on coagulation function and postoperative outcomes in patients with UC. METHODS: This retrospective cohort included 92 consecutive patients who underwent colectomy for UC. Postoperative coagulation indices and outcomes, including thromboelastography (TEG) findings and comprehensive complication index (CCI), were compared. The relative change in serum D-dimer (ΔD-dimer) levels and maximal amplitude (ΔMA) on TEG were also determined. RESULTS: Patients receiving PN supplemented with FO (n = 48) had lower D-dimer (P = .036) levels on postoperative day (POD) 5 and a higher MA (P < 0.001) on POD 1 than those who did not receive it (n = 44). A lower ΔD-dimer level (P = .048) and ΔMA (P < 0.001) were also observed in patients receiving FO. The incidence of major postoperative complications (6.3 vs 22.7%; P = .017) and CCI (20.9 vs 23.4%; P = .044) were significantly lower in patients receiving FO. In multivariate analysis, FO (odds ratio, 0.231; 95% confidence interval, 0.055-0.971; P = .046) was a positive protector of major postoperative complications. CONCLUSION: Perioperative PN supplemented with FO improved coagulation function and reduced major postoperative complications in patients with UC requiring colectomy. These results may provide cues in formulating management strategies for preventing thromboembolisms and postoperative complications in patients with UC.

[Research progress on bidirectional effect of microRNA on Alzheimer's disease and intervention with traditional Chinese medicine].

Alzheimer's disease(AD) is a chronic progressive neurodegenerative disease with recent memory impairment as the main clinical manifestation and senile plaques and neurofibrillary tangles as the main pathological changes. In recent years, the effect of microRNAs on AD has attracted widespread attention. Patients with AD have abnormal expression of miRNA, which is closed related to regulation of AD pathophysiology-related genes. Therefore, this paper first elaborated neuroprotective and toxic effects of microRNA in AD, and then explored relevant traditional Chinese medicines that can regulate miRNA in the treatment of AD, so as to provide basis for revealing the pathogenesis relationship between miRNA and AD and provide ideas for further development of anti-AD traditional Chinese medicine.

Use of the Water-Soluble Contrast Medium Gastrografin in Treatment of Adhesive Small Bowel Obstruction in Patients with and Without Chronic Radiation Enteropathy: A Single-Center Retrospective Study.

BACKGROUND This retrospective cohort study from a single center aimed to compare patient outcomes following the use of the water-soluble contrast medium Gastrografin in the treatment of adhesive small bowel obstruction (ASBO) in patients with and without a history of chronic radiation enteropathy (CRE). MATERIAL AND METHODS Fifty-nine patients with CRE-induced small bowel obstruction (SBO) and 53 patients with ASBO at Jinling Hospital between April 2014 and February 2018 were enrolled. The patients were given 100 ml Gastrografin through a naso-jejunal tube, and erect abdominal X-rays were taken. Risk factors were found to be correlated with successful non-operative management (SNM) through statistical analyses. RESULTS The success rate of conservative treatment was higher in the Gastrografin group than in the control group (P<0.05). The Gastrografin challenge test is predictive of need for surgery in CRE-induced SBO and ASBO (AUC=0.860 and 0.749, respectively). The predictors associated with SNM in the CRE-induced SBO group were the total dose of radiotherapy, the Gastrografin challenge test, and previous operations for SBO. In the ASBO group, the predictors were the Gastrografin challenge test and previous operations for SBO. The operation rate of SBO patients with Gastrografin treatment was significantly lower than that in the control group (P<0.05). CONCLUSIONS The findings from this study showed that the use of Gastrografin effectively resolved ASBO in patients with and without a history of CRE, but a long-term requirement for surgery could not be avoided. The Gastrografin challenge may be a useful test to predict surgical outcomes.

Synthesis, extracorporeal nephrotoxicity, and 3D-QSAR of andrographolide derivatives.

Andrographolide is a traditional Chinese medicine monomer with many pharmacological activities, but has potential nephrotoxicity. Here, we aim to investigate the relationship between modification of andrographolide structure and its nephrotoxicity. Twenty-three andrographolide derivatives were synthesized, and their structures were confirmed by 1 H-NMR and HRMS. Nephrotoxicity of these compounds against human renal tubular epithelial (HK-2) cells was evaluated using the MTT assay. The results indicated that most of them had significantly reduced nephrotoxicity, especially compounds III, V, and IXc , with IC50 values of 1,985, 1,300, and 806.9 µmol/L, respectively, which were obviously superior to andrographolide (IC50 30.60 µmol/L). However, compounds Ia -If (IC50 values < 30 µmol/L), the 14-OH derivatives of andrographolide, showed higher nephrotoxicity than that of andrographolide. Three-dimensional quantitative structure-activity relationship (3D-QSAR) models of COMFA and COMSIA were established (COMFA: q2  = 0.639, r2  = 0.951; COMSIA: q2  = 0.569, r2  = 0.857). This model allowed proposing five new compounds with lower theoretical nephrotoxicity, which would be worthwhile to synthesize and evaluate. We believe that predicted models will help us to understand the structural modification requirements of andrographolide to reduce the nephrotoxicity, and further investigations will be needed to determine the mechanism involved in the effect of less nephrotoxic compounds.

Protective Effects of Moderate Intensity Static Magnetic Fields on Diabetic Mice.

The purpose of this study was to investigate the effects of moderate-intensity static magnetic field (SMF) on diabetic mice. We studied the effects of SMF on blood glucose of normal mice by starch tolerance and glucose tolerance tests. Then, we evaluated the effects of SMF on blood glucose of diabetic mice by establishing alloxan-induced type 1 diabetic mice and high-fat diet + streptozotocin (STZ)-induced type 2 diabetic mice. The results showed that different magnetic field intensities and blank control did not affect the blood glucose of normal mice. After starch and glucose administration, different magnetic fields could improve the glucose tolerance of normal mice, and this was obvious in the 600 mT group. In the experiment of type 1 diabetic mice induced by alloxan, the results showed that different magnetic field intensities could improve the starch tolerance of mice, and that in the 400 mT group was obvious. In the experiment of type 2 diabetic mice induced by a high-fat diet + STZ, the 400 mT group could reduce food intake and water consumption in the later period. The 600 mT group could improve the starch tolerance of mice. The 400 and 600 mT groups could reduce fasting blood glucose. At the same time, total cholesterol and triglyceride decreased in different magnetic field intensities, and the 600 mT group could significantly increase the serum insulin content of mice. In summary, the results of this study suggest that SMF has a protective role in diabetic mice. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

Network Pharmacology Study of Heat-Clearing and Detoxifying Traditional Chinese Medicine for Alzheimer's Disease.

This study aims to explore the possible homologous mechanism of 7 frequently-used herbs for heat-clearing and detoxification in traditional Chinese medicine (HDTCM) for treating Alzheimer's disease (AD), one of the most common types of dementia, based on network pharmacology. Herbs that satisfied the criteria of containing chlorogenic acid, relating to AD and aligning with HDTCM, were simultaneously collected to determine whether they have anti-AD effect based on a survey of the literature. Herb-ingredient-target-disease networks were constructed by collecting information from the TCMSP and GeneCards public databases. The common targets of the herbs and AD were identified for conducting a Gene Ontology (GO) analyses and a Reactome pathway enrichment analysis. The results showed that PTGS1, IL-6, CASP3, and VEGFA were the predicted key gene targets. The IL-4 and IL-13 signaling pathway, the ESR-mediated signaling pathway, and the extranuclear estrogen signaling pathway were the significant pathways associated with the 7 herbs. This study revealed that the analogous anti-AD mechanism of the 7 herbs of HDTCM may be associated with anti-inflammation, which is a common effect of the chlorogenic acid and quercetin components.

Moderate Intensity Static Magnetic Fields Prevent Thrombus Formation in Rats and Mice.

We established three types of thrombosis models to explore the effects of the static magnetic field (SMF) on thrombosis in rats and mice with three different MF intensities. In the carrageenan-induced thrombosis model in rats, the SMF treatments reduced the black tail length of rats, extracorporeal thrombus, and the mass of wet and dry thrombus, and improved the coagulation index value. In FeCl3 -induced arterial thrombosis model in rats, the SMF treatment showed some anti-thrombotic effects. More specifically, the SMF treatment affected rodent blood pressure, plasma plasminogen activator inhibitor, tissue-type plasminogen activator, thrombus mass, and thrombus protein content. In the adrenaline-induced thrombosis model in mice, the SMF treatment had certain effects on the diameter and blood flow velocity of mouse auricle microcirculation in fine veins and arteries. Overall, the highest MF intensities we tested, 20-150 mT, showed a trend of anti-thrombotic effect, indicating that the moderate-intensity SMF might serve as a potential treatment for clot-related diseases in the future. Bioelectromagnetics. 2020;41:52-62 © 2019 Bioelectromagnetics Society.

A network-based analysis of key pharmacological pathways of Andrographis paniculata acting on Alzheimer's disease and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata (AP) is a native plant with anti-inflammatory and antioxidant properties and used as an official herbal medicine. Recently more and more researches have indicated that AP shows pharmacological effects on Alzheimer's disease (AD) but its mechanism is unclear. AIMS OF THE STUDY: Network pharmacology approach combined with experimental validation was developed to reveal the underlying molecular mechanisms of AP in treating AD. MATERIALS AND METHODS: The compounds of AP from TCM database, the AD-related targets from disease database and the targets corresponding to compounds from swissTargetPrediction were collected. Then DAVID database was used for annotation and enrichment pathways, meanwhile the compound-target, protein-protein interaction from String database and compound-target-pathway network was constructed, molecular modeling was performed using Sybyl-x. Okadaic acid (OKA)-induced cytotoxicity model in PC12 cells was established to verify the mechanism of AP and the key proteins were detected by western blotting. RESULTS: 28 AP components were identified after ADME filter analysis and 52 targets were gained via mapping predicted targets into AD-related proteins. In addition, after multiple network analysis, the 22 hub target genes were enriched onto pathways involved in AD, such as neuroactive ligand-receptor interaction, serotonergic synapse, Alzheimer's disease, PI3K-Akt and NF-kB signaling pathway. Interestingly, molecular docking simulation revealed that the targets including PTGS2, BACE1, GSK3B and IKBKB had good ability to combine with AP components. Experimental validation in an in vitro system proved that AP treatment obviously increased in levels inactive of p-GSK3ß (P < 0.05) and decreased in levels of BACE (P < 0.05), PTGS2 (namely COX2, P < 0.05) and NF-kB protein (P < 0.05) compare with OKA treated group. CONCLUSION: Our data provided convincing evidence that the neuroprotective effects of AP might be partially related to their regulation of the APP-BACE1-GSK3B signal axis and inflammation, which should be the focus of study in this field in the future.

Pseudo-allergic reaction caused by Qingkailing injection partially via the PI3K-Rac1 signaling pathway in RBL-2H3 cells.

Qingkailing injection (QKLI) is a kind of multi-component traditional Chinese medicine injection. It has been widely used in clinical practice, but in recent years, it has caused more and more adverse reactions, mainly manifested as pseudo-allergic symptoms. To explore the potential mechanism of the pseudo-allergic reaction by QKLI, basophilic leukemia cell line 2H3 (RBL-2H3) was chosen. The results showed that QKLI at doses of 5, 10 and 20 mL L-1 activated phosphoinositide 3-kinase (PI3K) activity and also increased the levels of Ras-related C3 botulinum toxin substrate 1 (Rac1), p21 protein-activated kinase 1 (Pak1), LIM kinase (Limk1) and cofilin (an actin polymerization regulator) proteins. What's more, QKLI aggravated the depolymerization of F-actin. NSC23766, a Rac1 inhibitor, reversed the previous results in QKLI-treated RBL-2H3 cells. In addition, when the Rac1 gene was knocked down using lentiviral vector-loaded shRNA in RBL-2H3 cells, the PI3K activity and depolymerization of F-actin were downregulated, hinting that the pseudo-allergic reaction was significantly reduced. In general, the pseudo-allergic reaction induced by QKLI was likely to be based on PI3K-Rac1 signaling pathways partially.

Use of gastrografin in the management of faecal impaction in patients with severe chronic constipation: a randomized clinical trial.

BACKGROUND/AIM: Faecal impaction (FI) is a common cause of lower gastrointestinal tract obstruction. Gastrografin is a water-soluble radiologic contrast agent that may be orally or rectally administered, with proved therapeutic benefits in adhesive small bowel obstruction. Enemas have long been advocated as the best treatment for FI. The purpose of this study was to demonstrate that enteral administration of gastrografin might be more effective than enema in FI treatment inducing intestinal obstruction. METHODS: A double-blinded, controlled and randomized trial was conducted. Participants received 100 mL of gastrografin (gastrografin group) through nasointestinal tube or enemas (enema group) once daily for six consecutive days. Successful faecal disimpaction, FI time to resolution, Bristol Stool Scale, constipation severity, symptom assessment and adverse events were evaluated. RESULTS: A total of 124 patients were eligible, but only 83 were enrolled to this trial (mean age: 44 ± 15.8 years). Forty-two patients received enemas, and 41 patients received gastrografin, with six dropouts in each group. Successful disimpaction was achieved with enemas (69.44%) and gastrografin (88.57%; P = 0.034), mean duration of impaction was strikingly different between the two groups (67.13 versus 31.67, respectively; P < 0.01). Constipation severity and symptom assessment were significantly reduced in the gastrografin group. CONCLUSION: Gastrografin given through nasointestinal tube was more effective than enema in the treatment of FI inducing colon obstruction. Gastrografin might be taken into consideration as an effective and safe therapeutic option for FI.

Andrographolide Protects PC12 Cells Against ß-Amyloid-Induced Autophagy-Associated Cell Death Through Activation of the Nrf2-Mediated p62 Signaling Pathway.

Recent studies mentioned that Andrographolide (Andro), the main bioactive component of traditional Chinese medicine Andrographis paniculata, may be a potential natural product for treating Alzheimer's disease, but the underlining mechanism remains to be discovered. In this study, we investigated whether Andro regulates the nuclear factor E2-related factor 2 (Nrf2)/Sequestosome 1 (p62) signaling pathway and activates autophagy to protect neuronal PC12 cells from the toxicity of the ß-amyloid (Aß) peptide. Our results revealed that Andro protected and rescued PC12 cells from Aß1⁻42-induced cell death and restored abnormal changes in nuclear morphology, lactate dehydrogenase, malondialdehyde, intracellular reactive oxygen species, and mitochondrial membrane potential. RT-PCR and Western blotting analysis demonstrated that Andro activated autophagy-related genes and proteins (Beclin-1 and LC3); meanwhile, it also augmented the Nrf2 and p62 expression in mRNA and protein levels, and reduced p-tau and p21 protein expression in Aß1⁻42-stimulated cells. Then, further study showed that the pre-transfection of cells with Nrf2 small interfering RNA (siRNA) resulted in the downregulation of p62, Beclin-1, and LC3 proteins expression, as well as the upregulation of p21. Furthermore, the pre-transfection of cells with p62 siRNA didn't block the Nrf2 protein expression, accompanying with an elevated p21. Taken together, these results showed that Andro significantly ameliorated cell death due to Aß1⁻42 insult through the activation of autophagy and the Nrf2-mediated p62 signaling pathway.

Long-term follow-up of the effects of fecal microbiota transplantation in combination with soluble dietary fiber as a therapeutic regimen in slow transit constipation.

As some studies have reported that strategies targeting the gut microbiota such as fecal microbiota transplantation (FMT) with or without other microecological therapy might have efficacy in treating slow transit constipation (STC), we conducted a single-center, open-label trial to study the long-term effect of FMT combined with soluble dietary fiber (pectin) on STC. Thirty-one adult patients with STC were enrolled into the trial. Patients received 6-day FMT procedures repeatedly for the first 3 months and soluble dietary fiber (pectin) daily during the follow-up. The rate of clinical remission and improvement, stool consistency, the Wexner constipation scale, and assessment of constipation-related symptoms were evaluated at week 4 and 1 year later. The clinical remission and improvement rates at week 4 were 69.0% (20/29) and 75.9% (22/29), respectively. At the end of the study, 48.3% (14/29) of patients continued to have at least three complete spontaneous bowel movements per week and 58.6% (17/29) of patients showed clinical improvements. Stool consistency, the Wexner constipation scale, and constipation symptoms improved both at short-term and long-term follow-up. The results indicated that FMT in combination with soluble dietary fiber (pectin) had both short-term and long-term efficacy in treating STC.

HBVcircle: A novel tool to investigate hepatitis B virus covalently closed circular DNA.

BACKGROUND & AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists as a stable episome in infected hepatocytes and serves as a template for the transcription of all viral genes. Due to the narrow host range of HBV, the development of a robust mouse model that supports cccDNA-dependent viral replication is a key hurdle in the development of novel HBV therapeutics. This study aimed to develop a novel tool to investigate HBV cccDNA. METHODS: Through minicircle technology, HBVcircle, a recombinant cccDNA, was easily generated and extracted from a genetically engineered E. coli strain. We characterized the performance of HBVcircle in cell culture by transfection and in immunocompetent mice by hydrodynamic injection (HDI). RESULTS: We demonstrated that HBVcircle formed authentic cccDNA-like molecules in vitro in transiently transfected hepatic cells and in vivo in mouse liver after HDI. HBVcircle supported high levels and persistent HBV replication. In addition, we investigated different factors affecting HBV in vivo replication and persistence, including the host genetic background, vector design and dosage, viral genes and genotypes, and immune activation status. Furthermore, different classes of anti-HBV drugs were also assessed with the HBVcircle system. CONCLUSION: Compared with previous reported HBV mouse models which employ other viral vectors to introduce overlength HBV genomes, viral gene expression and associated phenotypes are entirely driven by cccDNA-like viral genomes in the HBVcircle mouse model. Therefore, the HBVcircle is a close mimic of cccDNA, and it represents a novel tool for addressing HBV cccDNA related biological questions and for anti-HBV drug discovery. LAY SUMMARY: To establish a mouse model that supports cccDNA-dependent transcription, a novel tool named HBVcircle, was developed with minicircle technology. HBVcircle formed authentic cccDNA-like molecules in hepatocytes, and supported high levels and persistent HBV replication in vivo. The HBVcircle is a close mimic of cccDNA, and it represents a novel tool for addressing HBV cccDNA related biological questions and for anti-HBV drug discovery.

Cyclic nucleotide-gated channel 18 functions as an essential Ca2+ channel for pollen germination and pollen tube growth in Arabidopsis.

We recently revealed that cyclic nucleotide-gated channel 18 (CNGC18) functioned as the main Ca2+ channel in pollen tube tips for pollen tube guidance to ovules by regulating external Ca2+ influx in Arabidopsis. In this study, we found that the reduction of external Ca2+ concentration ([Ca2+]ext) from 10 mM to 5 mM, and further to 2 mM, led to the decreases of pollen germination percentages, but led to the increases of the percentages of ruptured pollen grains and tubes, and branched pollen tubes in vitro in cngc18-17 compared with wild type. The second point mutant allele cngc18-22 showed similar phenotypes, including reduced pollen germination percentages, increased percentages of ruptured pollen tubes, but did not show obvious different percentages of ruptured pollen grains and branched pollen tubes compared with wild type. These data demonstrate that CNGC18 plays essential roles in pollen germination and tube growth as a Ca2+ channel in Arabidopsis.

[Short-term efficacy on fecal microbiota transplantation combined with soluble dietary fiber and probiotics in the treatment of slow transit constipation].

OBJECTIVE: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) combined with soluble dietary fiber and probiotics for slow transit constipation(STC). METHODS: Twenty-three patients with STC from Jinling Hospital, Medical School of Nanjing University were prospectively enrolled between April 2015 and January 2016. STC patients received FMT combined with soluble dietary fiber and probiotics. Fresh stool(100 g) was immediately mixed in a blender with 500 ml of 0.9% sterile saline for several seconds, which was then filtered through a gauze pad and a decreasing number of gauze screen (2.0 to 0.5 mm). The fecal bacteria suspension was stored frozen at -20centi-degree. The preparation time of FMT material was less than 1 hour. Total time of treatment was 9 days. An initial oral antibiotics(vancomycin 500 mg orally twice per day) was given for 3 consecutive days. Then the fecal microbiota(100 ml) was infused slowly(5 min) through nasojejunal tube for 6 consecutive days. After FMT, patients were recommended to receive soluble dietary fiber (pectin, 8 g/d) and probiotics (bifid triple viable capsules, twice per day) for 4 weeks. Rates of clinical improvement and remission, adverse events, constipation-related symptoms (PAC-SYM scores), bowel movements per week and gastrointestinal quality-of-life index (GIQLI) were recorded during the 12-week follow-up. This study was registered in the Clinical Trials.gov (NCT02016469). RESULTS: Among 23 patients, 7 were male, 16 were female, the mean age was (49.6±14.7) years, the body mass index was (21.2±2.2) kg/m2, the duration of constipation was (8.3±5.9) years, and the defecation frequency was 1.8±0.7 per week. Compared with pre-treatment, PAC-SYM scores decreased significantly from 2.3±0.5 to 1.3±0.4 at week 12 (P<0.01), defecation frequency increased from 1.8±0.7 per week to 4.8±2.0 per week at week 12 (P<0.01), and patients felt satisfied with improved GIQLI score (from 78.5±15.5 to 120.8±21.3, P<0.01). During the follow-up, the clinical improvement and remission of STC patients reached 69.6%(16/23) and 52.2%(12/23), respectively. No serious adverse events were observed. CONCLUSION: FMT combined with soluble dietary fiber and probiotics is safe and effective in treating slow transit constipation, which can improve the symptom and quality of life significantly.

Pectin enhances the effect of fecal microbiota transplantation in ulcerative colitis by delaying the loss of diversity of gut flora.

BACKGROUND: Fecal microbiota transplantation (FMT) induces remission in ulcerative colitis (UC). However, the treatment effect of FMT diminishes over time. Maintaining the diversity of the gut flora for long periods may improve the effects of FMT in UC. Pectin, which can be fermented by gut microbiota into short-chain fatty acids, is postulated to shape the composition and maintain the balance of gut microbiota following transplantation. This study investigated whether pectin could enhance the effects of FMT in UC patients. RESULTS: Three FMT patients and four FMTP patients achieved the primary outcome. The Mayo scores of the FMTP group were lower than those of the FMT group at weeks 4 and 12 (P = 0.042 and P = 0.042, respectively). There were no differences in the diversity of the gut flora between the two groups at weeks 4 and 12; however, the composition of the gut flora of the FMTP group was more similar than the FMT group to that of the donor at all-time points post-treatment. CONCLUSIONS: Pectin decreased the Mayo score by preserving the diversity of the gut flora following FMT for UC. TRIAL REGISTRATION: Current Controlled Trial NCT02016469 . Registered 10 November 2013.

Mucosal MicroRNAs Expression Profiles before and after Exclusive Enteral Nutrition Therapy in Adult Patients with Crohn's Disease.

MicroRNAs (miRNAs) have been shown to be important for the pathogenesis of Crohn's disease (CD). Exclusive enteral nutrition (EEN) is an effective therapy for inducing remission in CD. We aimed to investigate the alteration of miRNAs expression profile in the terminal ileal mucosa of CD patients before and after EEN. Twenty-five patients and ten healthy individuals were included. MiRNAs expression profile was firstly assessed using microarray technology and then validation was performed by qRT-PCR. The correlations between miRNAs and CD activity index (CDAI) score and serum C-reactive protein (CRP) level were also evaluated. Microarray analysis showed that mucosal miRNAs expression profile after EEN therapy was significantly changed compared with inflamed mucosa before treatment, and was most similar to the healthy one among all CD groups. Altered expressions of hsa-miR-192-5p, hsa-miR-423-3p, hsa-miR-99a-5p, hsa-miR-124-3p, hsa-miR-301a-5p, hsa-miR-495-5p, and hsa-let-7b-5p were confirmed by qRT-PCR. hsa-let-7b-5p was significantly correlated with serum CRP levels before and after EEN treatment (r = -0.518, p = 0.008, and r = -0.569, p = 0.003). Our study showed EEN induction therapy was associated with a trend for normalizing of the mucosal miRNAs expression profile, and expression of mucosal hsa-let-7b-5p was correlated with serum CRP level in patients with CD.

Oxymatrine Induces Liver Injury through JNK Signalling Pathway Mediated by TNF-α In Vivo.

Oxymatrine (OMT) is a traditional Chinese medicine monomer and has been used for the treatment of chronic viral hepatitis and many other diseases. We aimed to investigate whether OMT could induce hepatotoxicity in mice and explored the preliminary mechanisms of toxic effects. Twenty-four Institute for Cancer Research male mice were randomly divided into four groups: control group, 40, 160 and 320 mg/kg OMT-treated group. OMT was orally administered once daily for 7 days. The OMT-treated group exhibited an improved liver index and increase in serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase,augmented liver histological injury, elevated levels of malondialdehyde and tumour necrosis factor alpha (TNF-α) accompanied by the activation of caspase-9/-8/-3, up-regulated expressions of tumour necrosis factor receptor l (TNFR1), TNF receptor-associated structure domain (TRADD) and phosphorylation of stress-activated protein kinase/c-jun N-terminal protein kinases (p-SAPK/JNK). Altogether, these results suggest that OMT at a dose of 320 mg/kg leads to liver damage and is related to the activation of JNK signalling pathway mediated by TNF-α in the liver of mice.

Role of exclusive enteral nutrition in the preoperative optimization of patients with Crohn's disease following immunosuppressive therapy.

We conducted a study to evaluate the impact of the exclusive enteral nutrition (EEN) on perioperative outcome in Crohn's disease (CD) patients following immunosuppressive therapy. Patients with CD followed at a referral center between January 2001 and March 2014 who underwent abdominal surgery were identified. Patients were divided into 4 groups: patients not exposed to immunosuppressive agents in the previous 8 weeks before surgery (group 1); patients received immunosuppressive medications without preoperative drug-free interval (group 2); patients had preoperative immunosuppressants-free interval (group 3); patients treated with adding EEN to preoperative immunosuppressants-free interval regimen (group 4). Urgent operation requirement, stoma creation, postoperative complications, readmission, and reoperation were compared in patients among groups. Overall, 708 abdominal surgeries performed in 498 CD patients were identified. Three hundred seventy-six (53.11%) surgeries performed in those receiving preoperative immunosuppressive medications. Compared with other groups, group 2 had increased postoperative complications, more frequent urgent operation, and higher rate of stoma creation. Patients in group 4 were found to have better outcome including lower rate of stoma creation (P < 0.05), and decreased incidence of postoperative complications (P < 0.05) compared with group 2 and group 3. Additionally, decreased urgent operation requirement (P < 0.05) and extended preoperative drug-free interval (P < 0.001) were observed in the group 4 than those in the group 3. Preoperative optimization of CD following immunosuppressive therapy by EEN prolongs the immunosuppressants-free interval, reduces the risk of urgent surgery and reoperation, and most importantly, decreases complications after abdominal surgery.