Efficacy and safety of moxibustion for ulcerative colitis: protocol for a systematic review and meta-analysis.

INTRODUCTION: Ulcerative colitis (UC) is a global chronic inflammatory bowel disease, and the poor efficacy of currently available pharmacological regimens makes the management of UC a great challenge. Moxibustion has shown great potential in the management of UC. However, its effectiveness and safety are still controversial. The purpose of this study is to synthesise the latest evidence regarding the clinical efficacy and safety of moxibustion for UC. METHODS AND ANALYSIS: The Cochrane Library, PubMed, EMBASE, CNKI, Wanfang, VIP and SinoMed databases will be searched from inception to July 2023, to identify all randomised controlled trials with moxibustion for UC. The primary outcome will be clinical efficacy, as measured by validated scales. The serum inflammatory factor, colonoscopy results, quality of life, recurrence rate and adverse events will be the secondary outcomes. The Cochrane Risk of Bias 2.0 tool will be used to assess the methodological quality of each included trial. All data extraction will be carried out independently by two investigators. RevMan V.5.4 software will be used for data analysis and Cochran's Q statistic and I2 test will be used to assess heterogeneity between studies. In addition, we will perform subgroup analyses, sensitivity analyses and publication bias if the available data are sufficient. The strength of evidence will be graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. ETHICS AND DISSEMINATION: Ethics approval is not required for this review. Our findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023425481.

Coffee and caffeine intake reduces risk of ulcerative colitis: a case-control study in Japan.

BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.

Association between dietary acid load and the odds of ulcerative colitis: a case-control study.

Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBDs), which have a pivotal role in weakening the quality of lives of suffering patients. According to some recent studies, significant changes in dietary patterns may have contributed to the increased prevalence of UC. Potential renal acid load (PRAL) is an index used to estimate dietary acid load of the diet. The aim of the current study is to investigate the association between PRAL and odds of UC. The current case-control study included 62 newly diagnosed cases of UC and 124 healthy controls. Dietary habits of participants in the last year were collected with a valid food frequency questionnaire (FFQ). Thereafter, PRAL score was calculated based on a formula containing the dietary intake of protein, phosphorus, potassium, calcium, and magnesium. Participants were categorized according to quartiles of PRAL. Multivariable logistic regression models were used to estimate the odds' ratio (OR) with 95% confidence intervals (CIs) of UC across quartiles of PRAL. The results of the current study indicated that in the crude model, participants in the fourth quartile of PRAL had 2.51 time higher odds of UC compared with those in the first quartile of the PRAL [(OR 2.51; 95% CI 1.03-6.14), (P = 0.043)]. After adjustment for age and biological gender, this positive association remained significant [(OR 2.99; 95% CI 1.16-7.72), (P = 0.023)]. In the final model, after further adjustment for BMI, current smoking, education, Helicobacter pylori infection, and dietary intakes of total energy, omega-3 fatty acids, trans-fatty acids, and total dietary fiber, the odds of UC in the highest quartile of PRAL was significantly higher compared to the lowest quartile [(OR 3.08; 95% CI 1.01-9.39), (P = 0.048)]. So, we observed that higher dietary acid load assessed by PRAL score is associated with greater odds of UC.

Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis.

Fecal microbiota transplant is a promising therapy for ulcerative colitis. Parameters maximizing effectiveness and tolerability are not yet clear, and it is not known how import the transmission of donor microbes to patients is. Here (clinicaltrails.gov: NCT03006809) we have tested the effects of antibiotic pretreatment and compared two modes of maintenance dose delivery, capsules versus enema, in a randomized, pilot, open-label, 2 × 2 factorial design with 22 patients analyzed with mild to moderate UC. Clinically, the treatment was well-tolerated with favorable safety profile. Of patients who received antibiotic pretreatment, 6 of 11 experienced remission after 6 weeks of treatment, versus 2 of 11 non-pretreated patients (log odds ratio: 1.69, 95% confidence interval: -0.25 to 3.62). No significant differences were found between maintenance dosing via capsules versus enema. In exploratory analyses, microbiome turnover at both the species and strain levels was extensive and significantly more pronounced in the pretreated patients. Associations were also revealed between taxonomic turnover and changes in the composition of primary and secondary bile acids. Together these findings suggest that antibiotic pretreatment contributes to microbiome engraftment and possibly clinical effectiveness, and validate longitudinal strain tracking as a powerful way to monitor the dynamics and impact of microbiota transfer.

Role of vitamin D in ulcerative colitis: an update on basic research and therapeutic applications.

INTRODUCTION: Vitamin D deficiency is common in patients with ulcerative colitis (UC). Moreover, vitamin D supplementation seems to contribute to disease relief. Nevertheless, the exact etiological link between vitamin D deficiency and UC is far from clear, and an agreement has not been reached on the frequency and dosage of vitamin D supplementation required. AREAS COVERED: This review will outline the possible role of vitamin D in the pathogenesis of UC and summarize the current state of clinical research on vitamin D. Literature was searched on PUBMED, with 'Vitamin D,' 'Ulcerative colitis,' 'Vitamin D receptor,' and 'disease activity' as MeSH Terms. Relevant information is presented in figures or tables. EXPERT OPINION: The etiological relationship between vitamin D and the onset of UC is still being researched. More high-quality double-blind randomized clinical studies are needed to determine the efficacy of vitamin D supplementation in the treatment of UC, whether as the main treatment or as an adjuvant treatment. Importantly, determining the dosage and frequency of vitamin D supplementation should be the main research direction in the future, and regional factors should also be fully considered in this respect.

Hyperbaric oxygen therapy in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Translational data suggest a potential role of hyperbaric oxygen therapy (HBOT) in a subset of patients with inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis for the efficacy and safety of HBOT in IBD. METHODS: We searched Pubmed, Embase and CENTRAL to identify studies reporting the efficacy of HBOT in ulcerative colitis or Crohn's disease. We pooled the response rates for HBOT in ulcerative colitis and Crohn's disease separately. RESULTS: A total 18 studies were included in the systematic review and 16 in the analysis. The overall response rate of HBOT in ulcerative colitis was 83.24% (95% confidence interval: 61.90-93.82), while the response in Crohn's disease was 81.89 (76.72-86.11). The results of randomized trials for HBOT as adjuvant therapy in ulcerative colitis were conflicting. The complete healing of fistula in fistulizing Crohn's disease was noted 47.64% (22.05-74.54), while partial healing was noted in 34.29% (17.33-56.50%). Most of the adverse events were minor. CONCLUSION: Observational studies suggest benefit of use of HBOT in ulcerative colitis flares and Crohn's disease. However, adequately powered randomized trials are needed to draw a definite conclusion.

CD39/CD73/A2a Adenosine Metabolic Pathway: Targets for Moxibustion in Treating DSS-Induced Ulcerative Colitis.

Ulcerative Colitis (UC) is a chronic inflammation disease, and the incidence of UC is increasing recently. Both clinical trials and animal experiments show that moxibustion is a complementary and alternative treatment for UC. Previous studies showed that moxibustion can improve UC by regulating the balance of Tregs and Th17 (Sun et al., 2017). Treg cells is one subset of CD4[Formula: see text] T cells that exert the immunosuppressive function. CD39 and CD73, expressed on the surface of Tregs, hydrolyze ATP to AMP and are further involved in the immunosuppressive function of Tregs. In this study, we investigated the effect of moxibustion on CD39[Formula: see text] Tregs and CD73[Formula: see text] Tregs in dextran sulfate sodium (DSS) induced UC mice. The A2a receptor (A2aR), one of the targets of adenosine, was also detected. The results showed that moxibustion could increase the expression of CD39, CD73, and A2aR in colonic tissue and improve the proportion of CD39[Formula: see text] Tregs and CD73[Formula: see text] Tregs in peripheral blood, inguinal draining lymph nodes and spleen in the UC model. Additionally, A2aR agonists enhanced the cell viability of colonic epithelial cells and inhibit the production of cytokines IL-6 and TNF-[Formula: see text] in vitro, which may further influence the pathway of ATP purine signal metabolism and alleviates the gut inflammation of UC mice. Taken together, this study provides supplemental evidence to reveal the immune related mechanism of moxibustion in the treatment of UC.

Environmental factors associated with biological use and surgery in inflammatory bowel disease.

BACKGROUND AND AIM: While major efforts were made studying the complex etiology of inflammatory bowel disease (IBD) including environmental factors, less is known about underlying causes leading to the heterogeneous and highly variable course of disease. As cigarette smoking cessation is the best-known environmental factor with beneficial effect in Crohn's disease (CD), more exposome factors are likely involved. Further insights into the role of the exposome in heterogeneity of disease might not only further knowledge of underlying pathways, but also allow for better risk stratification. METHODS: Seven hundred twenty-eight IBD patients completed the validated Groningen IBD Environmental Questionnaire, collecting exposome data for 93 exposome factors. Associations with disease course, that is, for need for surgery or biological therapy, were evaluated using univariate and multivariate-adjusted logistic regression modeling. RESULTS: No significant associations were seen after Bonferroni correction. However, 11 novel exposome factors were identified with P < 0.05. Two factors were associated with course of CD and ulcerative colitis (UC): beer (CD OR0.3/UC OR0.3) and cannabis (0.5/2.2). While in CD, carpet flooring (0.5) was associated with biological use, and four factors were associated with surgery: working shifts (1.8), appendectomy (2.4), frequent tooth brushing (2.8), and large household size (0.1). For UC, migrants more often required biologicals (10.2). Childhood underweight (3.4), amphetamine use (6.2), and cocaine use (4.8) were associated with surgery. Five factors were replicated. CONCLUSIONS: We identified 16 environmental factors nominally associated with biological use and surgery in established IBD. These new insights form an important stepping stone to guide research on biological pathways involved, risk stratification, tailor-made interventions, and preventive strategies in IBD.

Depression in individuals who subsequently develop inflammatory bowel disease: a population-based nested case-control study.

OBJECTIVE: Depression is a potential risk factor for developing IBD. This association may be related to GI symptoms occurring before diagnosis. We aimed to determine whether depression, adjusted for pre-existing GI symptoms, is associated with subsequent IBD. DESIGN: We conducted a nested case-control study using the Clinical Practice Research Datalink identifying incident cases of UC and Crohn's disease (CD) from 1998 to 2016. Controls without IBD were matched for age and sex. We measured exposure to prevalent depression 4.5-5.5 years before IBD diagnosis. We created two sub-groups with prevalent depression based on whether individuals had reported GI symptoms before the onset of depression. We used conditional logistic regression to derive ORs for the risk of IBD depending on depression status. RESULTS: We identified 10 829 UC cases, 4531 CD cases and 15 360 controls. There was an excess of prevalent depression 5 years before IBD diagnosis relative to controls (UC: 3.7% vs 2.7%, CD 3.7% vs 2.9%). Individuals with GI symptoms prior to the diagnosis of depression had increased adjusted risks of developing UC and CD compared with those without depression (UC: OR 1.47, 95% CI 1.21 to 1.79; CD: OR 1.41, 95% CI 1.04 to 1.92). Individuals with depression alone had similar risks of UC and CD to those without depression (UC: OR 1.13, 95% CI 0.99 to 1.29; CD: OR 1.12, 95% CI 0.91 to 1.38). CONCLUSIONS: Depression, in the absence of prior GI symptoms, is not associated with subsequent development of IBD. However, depression with GI symptoms should prompt investigation for IBD.

Scutellaria baicalensis Georgi polysaccharide ameliorates DSS-induced ulcerative colitis by improving intestinal barrier function and modulating gut microbiota.

The aim of this study was to investigate the effect of a polysaccharide from Scutellaria baicalensis Georgi on UC. Gut microbiota dysbiosis is a worldwide problem associating with ulcerative colitis. One homogeneous polysaccharide, named SP2-1, was isolated from Scutellaria baicalensis Georgi. SP2-1 comprised mannose, ribose, rhamnose, glucuronic acid, glucose, xylose, arabinose, fucose in the molar ratio of 5.06:21.24:1.00:20.25:3.49:50.90:228.77:2.40, with Mw of 3.72 × 106 Da. SP2-1 treatment attenuated body weight loss, reduced DAI, ameliorated colonic pathological damage, and decreased MPO activity of UC mice induced by DSS. SP2-1 also suppressed the levels of proinflammatory cytokines. Additionally, the intestinal barrier was repaired due to the up-regulated expressions of ZO-1, Occludin and Claudin-5. SP2-1 remarkably enhanced the levels of acetic acid, propionic acid, and butyric acid in DSS-treated mice. Furthermore, as compared with model group, the abundance of Firmicutes, Bifidobacterium, Lactobacillus, and Roseburia were significantly increased with SP2-1 treatment. And SP2-1 could significantly inhibit the levels of Bacteroides, Proteobacteria and Staphylococcus. In conclusion, SP2-1 might serve as a novel drug candidate against UC.

Protective Effect of Cicer arietinum L. (Chickpea) Ethanol Extract in the Dextran Sulfate Sodium-Induced Mouse Model of Ulcerative Colitis.

Inflammatory bowel disease (IBD) is a major risk factor of colorectal cancer. Drugs currently used for IBD exhibit adverse effects including vomiting, nausea, and diarrhea. Naturally derived novel alternative therapies are required to overcome these limitations. In this study, we investigated the protective effects of ethanol extract of Cicer arietinum (CEE) in a dextran sodium sulfate (DSS)-induced mouse model of colitis. CEE markedly improved DSS-induced clinical symptoms and histological status, such as the disease activity index, spleen weight, and colon length. Moreover, CEE-treated mice showed significant recovery of DSS-induced crypt damage and cell death. CEE suppressed myeloperoxidase (MPO) activity and macrophage marker F4/80 mRNA expression in colonic tissue of mice with DSS-induced colitis, indicating neutrophil infiltration and macrophage accumulation, respectively. Although DSS upregulated pro-inflammatory mediators and activated transcription factors, CEE downregulated the mRNA expression of cytokines including interleukin-6, interleukin-1ß, and tumor necrosis factor-α, protein expression of cyclooxygenase-2 and inducible nitric oxide synthase, as well as activation of nuclear factor-kappa B (NF-кB) and signal transducer and activator of transcription 3 (STAT3). Hence, our findings reveal that the anti-inflammatory properties of CEE, involving the downregulation of the expression of pro-inflammatory mediators by inactivating NF-кB and STAT3 in DSS-induced colitis mice.

Vitamin D suppresses proangiogenic factors in patients with ulcerative colitis: A randomized double blind placebo controlled clinical trial.

BACKGROUND: Angiogenesis and inflammation are involved in the pathogenesis of ulcerative colitis (UC). This study aimed to assess the effect of vitamin D on serum levels of proangiogenic factors, visfatin and vascular endothelial growth factor (VEGF), in patients with UC. MATERIALS AND METHODS: Ninety patients were randomized to receive either a single intramuscular injection of 300,000 IU vitamin D or normal saline. Visfatin, VEGF, and 25-hydroxyvitamin D [25(OH)D] concentrations were assessed before and 90 days after the intervention. RESULTS: There were no significant differences in visfatin and VEGF levels between the two groups following supplementation. In patients with vitamin D insufficiency, visfatin increase was significantly lower in the intervention versus placebo group. There was an inverse correlation between serum 25(OH)D and visfatin in the subgroup with vitamin D insufficiency. CONCLUSION: Vitamin D might be beneficial in decreasing proangiogenic factors such as visfatin in UC patients with low 25(OH)D levels.

The Anti-inflammatory Effects of Dietary Anthocyanins against Ulcerative Colitis.

Ulcerative colitis (UC), which is a major form of inflammatory bowel disease (IBD), is a chronic relapsing disorder of the gastrointestinal tract affecting millions of people worldwide. Alternative natural therapies, including dietary changes, are being investigated to manage or treat UC since current treatment options have serious negative side effects. There is growing evidence from animal studies and human clinical trials that diets rich in anthocyanins, which are pigments in fruits and vegetables, protect against inflammation and increased gut permeability as well as improve colon health through their ability to alter bacterial metabolism and the microbial milieu within the intestines. In this review, the structure and bioactivity of anthocyanins, the role of inflammation and gut bacterial dysbiosis in UC pathogenesis, and their regulation by the dietary anthocyanins are discussed, which suggests the feasibility of dietary strategies for UC mitigation.

Beverage intake and risk of Crohn disease: A meta-analysis of 16 epidemiological studies.

Epidemiological studies were controversial in the association between beverage intake and risk of Crohn disease (CD). This study aimed to investigate the role of beverage intake in the development of CD. A systematic search was conducted in public databases to identify all relevant studies, and study-specific relative risks (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. Sixteen studies were identified with a total of 130,431 participants and 1933 CD cases. No significant association was detected between alcohol intake and CD risk (RR for the highest vs the lowest consumption level: 0.85, 95% CI 0.68-1.08), and coffee intake and the risk (RR 0.82, 95% CI 0.46-1.46). High intake of soft drinks was associated with CD risk (RR 1.42, 95% CI 1.01-1.98), and tea intake was inversely associated with CD risk (RR 0.70, 95% CI 0.53-0.93). In conclusion, high intake of soft drinks might increase the risk of CD, whereas tea intake might decrease the risk.

Vitamin D deficiency in adult patients with ulcerative colitis: Prevalence and relationship with disease severity, extent, and duration.

BACKGROUND: Vitamin D plays a key role in gut immunity and maintenance of the mucosal barrier. Vitamin D deficiency (VDD) worsens ulcerative colitis (UC) and its supplementation ameliorates the disease in mouse models. The prevalence and predictors of VDD in UC are not known. METHODS: Consecutive patients with UC (n = 80) underwent clinical, endoscopic, and histological evaluation to assess the extent, severity using UC disease activity index (UCDAI) score, and duration of illness. An equal number of age and gender-matched healthy adults without any features of inflammatory bowel disease (IBD) living in the same latitude were identified as controls. The serum 25-hydroxy vitamin D3 level was estimated. The subjects were classified as deficient (< 20 ng/mL), insufficient (20-32 ng/mL), sufficient (32-80 ng/mL), and optimal (> 80 ng/mL) based on vitamin D levels. Chi-square test and Mann-Whitney U test were done to identify factors associated with vitamin D deficiency. RESULTS: The patients and controls were similar in age and gender (40 ± 11.4 years, 51% male vs. 40 ± 12 years, 51% male; p = 1.000). Median vitamin D levels among patients were lower than the controls (18.1 ng/mL [IQR 14] vs. 32.5 ng/mL [IQR 36]; p < 0.001). Patients were more often VDD (56% vs. 40%) or insufficient (34% vs. 9%) and less often sufficient (9% vs. 40%) or optimal (1% vs. 11%), in contrast to controls (p < 0.001). Median vitamin D levels were lower in those with UCDAI > 6 (15 vs. 21 ng/mL; p = 0.01), having pancolitis (13 vs. 21 ng/mL, p = 0.01), and longer duration of illness > 2 years (13.8 vs. 20.8; p = 0.025). Vitamin D levels showed a negative correlation with frequency of stools (rho = - 0.244, p = 0.05), disease duration (rho = - 0.244, p = 0.007) and UCDAI score (r = - 0.348, p = 0.002). CONCLUSION: VDD is highly prevalent among patients with UC. Patients with longer disease duration, more severe symptoms, and pancolitis are likely to have lower vitamin D levels.

LB-9, Novel Probiotic Lactic Acid Bacteria, Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mice by Inhibiting TNF-α-Mediated Apoptosis of Intestinal Epithelial Cells.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a group of chronic and relapsing inflammatory conditions within the gastrointestinal tract. An increase in intestinal epithelial cell (IEC) apoptosis is a major characteristic of UC. Tumor necrosis factor-α (TNF-α) plays an essential role in the regulation of apoptosis. Aberrant activation of the immune response to resident microflora contributes to overproduction of TNF-α in the mucosal tissue of the gastrointestinal tract; a hallmark of UC. There are no curative medications for IBD. Thus, establishment of novel strategies for the treatment of this disease is imperative. Lactic acid bacteria (LAB) have been characterized as probiotics that can alleviate imbalances in indigenous microflora in UC, exhibiting beneficial effects for the treatment and prevention of IBD. In this study, we elucidate the potential of LB-9, a novel probiotic LAB, to protect against colitis development using a dextran sodium sulfate (DSS)-induced mouse model of UC. Treatment using LB-9 reduced clinical symptoms of colitis. In addition, both colitis-induced and NF-κB-mediated IEC apoptosis was markedly reduced in mice treated with LB-9. Moreover, these results were closely associated with reduced TNF-α levels. Our study demonstrates that the LB-9 probiotic exhibits therapeutic potential for UC through suppression of TNF-α-mediated IEC apoptosis in a murine DSS-induced colitis model, with important biological implications for treatment of IBD in humans.

Citrus aurantium L. and Its Flavonoids Regulate TNBS-Induced Inflammatory Bowel Disease through Anti-Inflammation and Suppressing Isolated Jejunum Contraction.

Inflammatory bowel disease (IBD) is a serious digestive system disease, for which the clinical therapeutic choices remain limited. Dried fruits of Citrus aurantium L. (CAL) are a traditional medicine used for regulation of the digestive system. The aim of this study was to identify the regulatory effects of CAL on IBD and to clarify the mechanism of the active compounds. In trinitrobenzene sulfonic acid-induced IBD rats, 125 to 500 mg/kg of oral CAL significantly alleviated weight loss and diarrhea, decreased colitis inflammatory cell infiltration, and inhibited pro-inflammatory cytokine production. The mechanisms of characteristic flavonoids in CAL were evaluated involving inflammation and intestine contraction aspects. Naringenin, nobiletin, and hesperetin showed anti-inflammatory effects on lipopolysaccharide-induced RAW cells. The mechanism may be related to the inhibition of the tumor necrosis factor-α (TNF-α)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway to suppress cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Naringenin and nobiletin showed inhibitory effects on isolated jejunum contraction. The mechanism of naringenin is partly related to COX, NOS, inositol triphosphate (IP3), and finally, to decreased jejunum motility. This study demonstrated that CAL, and its flavonoids' regulatory effects on IBD through anti-inflammation and inhibition of intestine muscle contraction, can provide basic information on developing new drugs or supplements against IBD based on CAL.

Herb-partitioned moxibustion alleviates colon injuries in ulcerative colitis rats.

AIM: To observe the effect of herb-partitioned moxibustion (HPM) on expression of colonic cytokines in ulcerative colitis (UC) rats. METHODS: A UC rat model was established by protein immunization in combination with topical chemical stimulation. Rats in the HPM group (n = 8) received HPM at bilateral Tianshu (ST25) points. The gross injury and pathological scores of the colon were recorded. The expression profile of colonic cytokines was assayed using the protein microarray technique. Specific differential cytokines were selected and verified by ELISA. The corresponding UniProt Accessions of the differentially expressed cytokines were retrieved in the UniProt database. The pathways involved were analyzed with the help of the KEGG PATHWAY database. The DAVID database was used for functional cluster and pathway analysis. RESULTS: HPM improved colon injuries in UC rats, manifested by accelerated repair of ulcers and alleviation of inflammation, and the gross injury and pathological scores both significantly decreased (P < 0.01). Fold change > 1.3 or < 0.77 was taken as the screening standard. There were 77 down-regulated and 9 up-regulated differentially expressed colonic cytokines in the HPM group compared with the model group, and expression of 20 differed significantly (P < 0.05). Twelve of the 20 significantly differentially expressed cytokines [ß-catenin, interleukin-1 receptor 6 (IL-1R6), IL-1ß, B7-1, nerve growth factor receptor, AMP-activated protein kinase-α1, neuropilin-2, orexin A, adipocyte differentiation-related protein, IL-2, Fas and FasL] were up-regulated in the model group (n = 3, compared with the normal group) but down-regulated in the HPM group (n = 3, compared with the model group). Functional cluster analysis showed that the differentially expressed colonic cytokines in the HPM group regulated apoptosis and protein phosphorylation. KEGG pathway analysis showed that 52 down-regulated and 7 up-regulated differentially expressed colonic cytokines in the HPM group had pathways. The pathways that interacted between the cytokines and their receptors accounted for the largest proportion (28 of the down-regulated and 5 of the up-regulated cytokines). CONCLUSION: HPM promotes the repair of colon injuries in UC rats, which is related to the regulation of several abnormally expressed cytokines.

Fat-soluble Vitamin Deficiencies and Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Vitamin deficiency is frequently associated with inflammatory bowel disease (IBD). Supplementation of vitamins could thus serve as an adjunctive therapy. The present meta-analysis reviews the deficiencies and alterations in serum fat-soluble vitamins (A, D, E, and K) reported in IBD patients. MATERIALS AND METHODS: PubMed database search was performed to identify all primary studies up to January 2015 that evaluated the serum concentrations of fat-soluble vitamin levels in IBD patients compared with healthy individuals. We estimated pooled mean differences between groups and estimated their relations with some compounding variables (age, disease duration, C-reactive protein, albumin), using a meta-regression analysis. RESULTS: Nineteen case-control studies met selection criteria. In patients with Crohn's disease (CD), vitamin A, D, E, K status was lower than in controls [D=212 µg/L.92; 95% confidence interval (CI), 95.36-330.48 µg/L, P=0.0002; D=6.97 nmol/L, 95% CI, 1.61-12.32 nmol/L, P=0.01; D=4.72 µmol/L, 95% CI, 1.60-7.84 µmol/L, P=0.003; D=1.46 ng/mL, 95% CI, 0.48-2.43 ng/mL, P=0.003, respectively]. Patients with ulcerative colitis had lower levels of vitamin A than controls (D=223.22 µg/L, 95% CI, 44.32-402.12 µg/L, P=0.01). Patients suffering from CD for a longer time had lower levels of vitamins A (95% CI=7.1-67.58 y, P=0.02) and K (95% CI, 0.09-0.71 y, P=0.02). Meta-regression analysis demonstrated statistically significant associations between the levels of inflammatory biomarkers: C-reactive protein (P=0.03, 95% CI, -9.74 to -0.6 mgl/L) and albumin (P=0.0003, 95% CI, 402.76-1361.98 g/dL), and vitamin A status in CD patients. CONCLUSION: Our meta-analysis shows that the levels of fat-soluble vitamins are generally lower in patients with inflammatory bowel diseases and their supplementation is undoubtedly indicated.

The neuroprotective effects of human bone marrow mesenchymal stem cells are dose-dependent in TNBS colitis.

BACKGROUND: The incidence of inflammatory bowel diseases (IBD) is increasing worldwide with patients experiencing severe impacts on their quality of life. It is well accepted that intestinal inflammation associates with extensive damage to the enteric nervous system (ENS), which intrinsically innervates the gastrointestinal tract and regulates all gut functions. Hence, treatments targeting the enteric neurons are plausible for alleviating IBD and associated complications. Mesenchymal stem cells (MSCs) are gaining wide recognition as a potential therapy for many diseases due to their immunomodulatory and neuroprotective qualities. However, there is a large discrepancy regarding appropriate cell doses used in both clinical trials and experimental models of disease. We have previously demonstrated that human bone marrow MSCs exhibit neuroprotective and anti-inflammatory effects in a guinea-pig model of 2,4,6-trinitrobenzene-sulfonate (TNBS)-induced colitis; but an investigation into whether this response is dose-dependent has not been conducted. METHODS: Hartley guinea-pigs were administered TNBS or sham treatment intra-rectally. Animals in the MSC treatment groups received either 1 × 105, 1 × 106 or 3 × 106 MSCs by enema 3 hours after induction of colitis. Colon tissues were collected 72 hours after TNBS administration to assess the effects of MSC treatments on the level of inflammation and damage to the ENS by immunohistochemical and histological analyses. RESULTS: MSCs administered at a low dose, 1 × 105 cells, had little or no effect on the level of immune cell infiltrate and damage to the colonic innervation was similar to the TNBS group. Treatment with 1 × 106 MSCs decreased the quantity of immune infiltrate and damage to nerve processes in the colonic wall, prevented myenteric neuronal loss and changes in neuronal subpopulations. Treatment with 3 × 106 MSCs had similar effects to 1 × 106 MSC treatments. CONCLUSIONS: The neuroprotective effect of MSCs in TNBS colitis is dose-dependent. Increasing doses higher than 1 × 106 MSCs demonstrates no further therapeutic benefit than 1 × 106 MSCs in preventing enteric neuropathy associated with intestinal inflammation. Furthermore, we have established an optimal dose of MSCs for future studies investigating intestinal inflammation, the enteric neurons and stem cell therapy in this model.