Therapeutic effect of curcumin on experimental colitis mediated by inhibiting CD8+CD11c+ cells.

AIM: To verify whether curcumin (Cur) can treat inflammatory bowel disease by regulating CD8+CD11c+ cells. METHODS: We evaluated the suppressive effect of Cur on CD8+CD11c+ cells in spleen and Peyer's patches (PPs) in colitis induced by trinitrobenzene sulfonic acid. Mice with colitis were treated by 200 mg/kg Cur for 7 d. On day 8, the therapeutic effect of Cur was evaluated by visual assessment and histological examination, while co-stimulatory molecules of CD8+CD11c+ cells in the spleen and PPs were measured by flow cytometry. The levels of interleukin (IL)-10, interferon (IFN)-γ and transforming growth factor (TGF)-ß1 in spleen and colonic mucosa were determined by ELISA. RESULTS: The disease activity index, colon weight, weight index of colon and histological score of experimental colitis were obviously decreased after Cur treatment, while the body weight and colon length recovered. After treatment with Cur, CD8+CD11c+ cells were decreased in the spleen and PPs, and the expression of major histocompatibility complex II, CD205, CD40, CD40L and intercellular adhesion molecule-1 was inhibited. IL-10, IFN-γ and TGF-ß1 levels were increased compared with those in mice with untreated colitis. CONCLUSION: Cur can effectively treat experimental colitis, which is realized by inhibiting CD8+CD11c+ cells.

Curcumin Suppressed Activation of Dendritic Cells via JAK/STAT/SOCS Signal in Mice with Experimental Colitis.

Dendritic cells (DCs) play a pivotal role as initiators in the pathogenesis of inflammatory bowel disease and are regulated by the JAK/STAT/SOCS signaling pathway. As a potent anti-inflammatory compound, curcumin represents a viable treatment alternative or adjunctive therapy in the management of chronic inflammatory bowel disease (IBD). The mechanism of curcumin treated IBD on DCs is not completely understood. In the present study, we explored the mechanism of curcumin treated experimental colitis by observing activation of DCs via JAK/STAT/SOCS signaling pathway in colitis mice. Experimental colitis was induced by 2, 4, 6-trinitrobenzene sulfonic acid. After 7 days treatment with curcumin, its therapeutic effect was verified by decreased colonic weight, histological scores, and remitting pathological injury. Meanwhile, the levels of major histocompatibility complex class II and DC costimulatory molecules (CD83, CD28, B7-DC, CD40, CD40 L, and TLR2) were inhibited and followed the up-regulated levels of IL-4, IL-10, and IFN-γ, and down-regulated GM-CSF, IL-12p70, IL-15, IL-23, and TGF-ß1. A key finding was that the phosphorylation of the three members (JAK2, STAT3, and STAT6) of the JAK/STAT/SOCS signaling pathway was inhibited, and the three downstream proteins (SOCS1, SOCS3, and PIAS3) from this pathway were highly expressed. In conclusion, curcumin suppressed the activation of DCs by modulating the JAK/STAT/SOCS signaling pathway to restore immunologic balance to effectively treat experimental colitis.

Curcumin improves regulatory T cells in gut-associated lymphoid tissue of colitis mice.

AIM: To explore the probable pathway by which curcumin (Cur) regulates the function of Treg cells by observing the expression of costimulatory molecules of dendritic cells (DCs). METHODS: Experimental colitis was induced by administering 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Forty male C57BL/6 mice were randomly divided into four groups: normal, TNBS + Cur, TNBS + mesalazine (Mes) and TNBS groups. The mice in the TNBS + Cur and TNBS +Mes groups were treated with Cur and Mes, respectively, while those in the TNBS group were treated with physiological saline for 7 d. After treatment, the curative effect of Cur was evaluated by colonic weight, colonic length, weight index of the colon, and histological observation and score. The levels of CD4(+)CD25+Foxp3(+) T cells (Treg cells) and costimulatory molecules of DCs were measured by flow cytometry. Also, related cytokines were analyzed by enzyme-linked immunosorbent assay. RESULTS: Cur alleviated inflammatory injury of the colonic mucosa, decreased colonic weigh and histological score, and restored colonic length. The number of Treg cells was increased, while the secretion of TNF-α, IL-2, IL-6, IL-12 p40, IL-17 and IL-21 and the expression of costimulatory molecules (CD205, CD54 [ICAM-1], TLR4, CD252[OX40 L], CD256 [RANK] and CD254 [RANK L]) of DCs were notably inhibited in colitis mice treated with Cur. CONCLUSION: Cur potentially modulates activation of DCs to enhance the suppressive functions of Treg cells and promote the recovery of damaged colonic mucosa in inflammatory bowel disease.

Astragalus polysaccharide attenuates rat experimental colitis by inducing regulatory T cells in intestinal Peyer's patches.

AIM: To explore probable mechanism underlying the therapeutic effect of Astragalus polysaccharide (APS) against experimental colitis. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups. Colitis was induced with 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The rats with colitis were treated with 400 mg/kg of APS for 7 d. The therapeutic effect was evaluated by colonic weight, weight index of the colon, colonic length, and macroscopic and histological scores. The levels of regulatory T (Treg) cells in Peyer's patches were measured by flow cytometry, and cytokines in colonic tissue homogenates were analyzed using enzyme-linked immunosorbent assay. The expression of related orphan receptor-γt (ROR-γt), IL-23 and STAT-5a was measured by Western blot. RESULTS: After 7-d treatment with APS, the weight index of the colon, colonic weight, macroscopical and histological scores were decreased, while the colonic length was increased compared with the model group. The expression of interleukin (IL)-2, IL-6, IL-17, IL-23 and ROR-γt in the colonic tissues was down-regulated, but Treg cells in Peyer's patches, TGF-ß and STAT5a in the colonic tissues were up-regulated. CONCLUSION: APS effectively ameliorates TNBS-induced experimental colitis in rats, probably through restoring the number of Treg cells, and inhibiting IL-17 levels in Peyer's patches.

Si Shen Wan Regulates Phospholipase Cγ-1 and PI3K/Akt Signal in Colonic Mucosa from Rats with Colitis.

The present study explored the feasible pathway of Si Shen Wan (SSW) in inhibiting apoptosis of intestinal epithelial cells (IECs) by observing activation of phospholipase Cγ-1 (PLC-γ1) and PI3K/Akt signal in colonic mucosa from rats with colitis. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in the Sprague-Dawley rats. After SSW was administrated for 7 days after TNBS infusion, western blot showed an increment in levels of PI3K, p-Akt, and IL-23 and a decrement in levels of PLC-γ1 and HSP70 in colonic mucosal injury induced by TNBS. Meanwhile, assessments by ELISA revealed an increment in concentrations of IL-2, IL-6, and IL-17 and a reduction in level of TGF-ß after TNBS challenge. Impressively, treatment with SSW for 7 days significantly attenuated the expressions of PI3K and p-Akt and the secretion of IL-2, IL-6, IL-17, and IL-23 and promoted the activation of PLC-γ1, HSP70, and TGF-ß. Our previous studies had demonstrated that SSW restored colonic mucosal ulcers by inhibiting apoptosis of IECs. The present study demonstrated that the effect of SSW on inhibiting apoptosis of IECs was realized probably by activation of PLC-γ1 and suppression of PI3K/Akt signal pathway.

[A comparative study of Bolton index in the youth and middle-aged and elderly people].

PURPOSE: To Investigate the changes of Bolton index, maxillary and mandibular teeth size and teeth size discrepancy (TSD) in the youth and middle- aged and elderly people. METHODS: One hundred ninety-one youth dental plaster casts from malocclusion patients and 63 middle-aged and elderly people with snoring or obstructive sleep apnea-hypopnea syndrome (OSAHS) patients were selected. 12 teeth size between the upper and lower first molar, width of maxillary lateral incisor, Bolton anterior and overall ratios and teeth size discrepancy were measured and calculated. Statistical analysis was performed using SPSS 13.0 software package. RESULTS: There was no significant difference between the 2 groups in Bolton anterior and overall ratios (P<0.05 ).The mean size of the upper lateral tooth in the youth was larger than the middle-aged and elderly people(P<0.01).There was no significant difference in 6 upper or lower anterior teeth size between canine and 12 mandibular teeth size between first molar in 2 groups, but the mean teeth size in the middle-aged and elderly people was smaller.The prevalence of anterior and overall TSD in the youth was 31.4% and 42.4%,while it was 19.05% and 15.9% in the middle-aged and elderly group. There was significant difference(P<0.05) between 2 groups in width of upper lateral incisor, which was 7.46mm in the youth and 7.20 mm in the middle-aged and elderly group. Prevalence of laminal width of upper lateral incisor in patients with teeth size discrepancy was low. CONCLUSIONS: Bolton index does not change by age. Although the teeth size in middle-aged and elderly group are smaller than the youth group, the total reduction is little without clinical significance. The laminal width of upper lateral incisor isn't the main cause for anterior or overall dental size discrepancy. Supported by Research Fund from Department of Public Health of Guangxi Zhuang Autonomous Region (GWZ2013405 and GWZ2007149).

Si Shen Wan Inhibits mRNA Expression of Apoptosis-Related Molecules in p38 MAPK Signal Pathway in Mice with Colitis.

Si Shen Wan (SSW) is used to effectively treat ulcerative colitis (UC) as a formula of traditional Chinese medicine. To explore the mechanism of SSW-inhibited apoptosis of colonic epithelial cell, the study observed mRNA expression of apoptosis-related molecules in p38 MAPK signal pathway in colonic mucosa in colitis mice treated with SSW. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice; meanwhile, the mice were administrated daily either SSW (5 g/kg) or p38 MAPK inhibitor (2 mg/kg) or vehicle (physiological saline) for 10 days. While microscopical evaluation was observed, apoptosis rate of colonic epithelial cell and mRNA expression of apoptosis-related molecules were tested. Compared with colitis mice without treatment, SSW alleviated colonic mucosal injuries and decreased apoptosis rate of colonic epithelial cell, while the mRNA expressions of p38 MAPK, p53, caspase-3, c-jun, c-fos, Bax, and TNF- α were decreased in the colonic mucosa in colitis mice treated with SSW, and Bcl-2 mRNA and the ratio of Bcl-2/Bax were increased. The present study demonstrated that SSW inhibited mRNA expression of apoptosis-related molecules in p38 MAPK signal pathway to downregulate colonic epithelial cells apoptosis in colonic mucosa in mice with colitis.

[Treatment of skeletal Class II adult patients with microscrew implant anchorage and multi-loop edgewise arch wire].

OBJECTIVE: To evaluate the effects and mechanisms of the microscrew implant anchorage (MIA) combined with multi-loop edgewise arch wire (MEAW) technique in the treatment of skeletal Class II adult patients. METHODS: Eleven adult patients with skeletal Class II high-angle malocclusions were treated with fixed appliances. The spaces were closed by the springs from the MIA to the hook on the archwire. The height of the hook and the direction of the force were different according to the intrusion and retraction of upper anterior teeth. In the finishing stage, MEAW technique and modified class II elastics (from the first loop of MEAW to the MIA) were used for final detailing. Cephalometric analysis was used to evaluate the effect after treatment. RESULTS: After treatment, the decrease of SNA, ANB and FMA were (2.86 +/- 1.05) degrees , (2.82 +/- 0.96) degrees and (2.95 +/- 1.35) degrees , respectively. The torque control of upper anterior teeth was good. The protrusion of lower incisors and the molar extrusion were avoided. The upper molars were moved distally by (3.00 +/- 2.19) mm. CONCLUSIONS: The treatment of adult patients with skeletal Class II high angle malocclusions with MIA and MEAW technique could not only improve the facial esthetics but also avoided the common side effects of traditional Class II elastics.