Objective To observe the therapeutic effect of thermosensitive hydrogel containing curcumin-vitamin E (VE) complex (hereinafter referred to as “curcumin-VE hydrogel”) on radiation-induced oral mucositis in mice. Methods Curcumin-VE hydrogel was prepared using the synthesized curcumin-VE complex as the carrier and poloxam as the substrate. The structure of curcumin-VE complex was characterized by Fourier transform infrared spectrometer, the microstructure of curcumin-VE hydrogel was determined by scanning electron microscope, and the gelation temperature was determined by rheometer, gel swelling and degradation were tested and gel adhesion was determined using a universal testing machine. Thirty healthy male BALB/C mice with specific pathogen free grade were randomly divided into three groups, with ten mice in each group. The radiation group and radiation+hydrogel group were modeled by a single high dose of radiation (25 Gy), while the control group had anesthesia but no radiation. The control group and radiation group were given daily feed and water 7 days after radiation. In addition to daily feed and water, the radiation+hydrogel group was given curcumin-VE hydrogel twice a day. The mice were sacreficed on the 8th day after radiation. The weight changes of each group were recorded after radiation. The ulceration area of tongue was measured by toluidine blue. The tongue of mouse were pathologically observed. The activities of superoxide dismutase, catalase (CAT), and glutathione peroxidase and the level of malondialdehyde in tongue tissue were determined. The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in tongue tissue were determined by enzyme linked immunosorbent assay. The distribution and positive expression of phosphorylated histone H2AX (γ-H2AX) and nuclear factor-erythroid 2-related factor 2 were determined by immunohistochemistry. Results Curcumin-VE hydrogel had a porous network structure and the gelation temperature was 30℃, the swelling rate was close to 300%, the gel degradation rate was up to 95% after 48 h, and the adhesion strength was 12.748 kPa. Compared with the radiation group, the weight of mice in the radiation+hydrogel group increased (P<0.05), the ulcer area decreased (P<0.05); the activity of CAT increased (P<0.05); the levels of TNF-α, IL-1β and IL-6 decreased (P<0.05); the expression of γ-H2AX was down-regulated (P<0.05). Conclusion Curcumin-VE hydrogel can delay or weaken the process of radiation-induced oral mucositis by reducing the DNA damage caused by radiation, inhibiting the production of reactive oxygen species, and effectively reducing the level of inflammation in tongue tissue.
ObjectiveTo develop an anti-inflammatory poly (lactic-co-glycolic acid) (PLGA) scaffold by loading xanthohumol, and investigate its anti-inflammatory and cartilage regeneration effects in goats. Methods The PLGA porous scaffolds were prepared by pore-causing agent leaching method, and then placed in xanthohumol solution for 24 hours to prepare xanthohumol-PLGA scaffolds (hereinafter referred to as drug-loaded scaffolds). The PLGA scaffolds and drug-loaded scaffolds were taken for general observation, the pore diameter of the scaffolds was measured by scanning electron microscope, the porosity was calculated by the drainage method, and the loading of xanthohumol on the scaffolds was verified by Fourier transform infrared (FTIR) spectrometer. Then the two scaffolds were co-cultured with RAW264.7 macrophages induced by lipopolysaccharide for 24 hours, and the expressions of inflammatory factors [interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α)] were detected by RT-PCR and Western blot to evaluate the anti-inflammatory properties in vitro of two scaffolds. Bone marrow mesenchymal stem cells (BMSCs) was obtained from bone marrow of a 6-month-old female healthy goat, cultured by adherent method, and passaged in vitro. The second passage cells were seeded on two scaffolds to construct BMSCs-scaffolds, and the cytocompatibility of scaffolds was observed by live/dead cell staining and cell counting kit 8 (CCK-8) assay. The BMSCs-scaffolds were cultured in vitro for 6 weeks, aiming to verify its feasibility of generating cartilage in vitro by gross observation, histological staining, collagen type Ⅱ immunohistochemical staining, and biochemical analysis. Finally, the two kinds of BMSCs-scaffolds cultured in vitro for 6 weeks were implanted into the goat subcutaneously, respectively. After 4 weeks, gross observation, histological staining, collagen type Ⅱ immunohistochemical staining, biochemical analysis, and RT-PCR were performed to comprehensively evaluate the anti-inflammatory effect in vivo and promotion of cartilage regeneration of the drug-loaded scaffolds. Results The prepared drug-loaded scaffold had a white porous structure with abundant, continuous, and uniform pore structures. Compared with the PLGA scaffold, there was no significant difference in pore size and porosity (P>0.05). FTIR spectrometer analysis showed that xanthohumol was successfully loaded to PLGA scaffolds. The in vitro results demonstrated that the gene and protein expressions of inflammatory cytokines (IL-1β and TNF-α) in drug-loaded scaffold significantly decreased than those in PLGA scaffold (P<0.05). With the prolongation of culture, the number of live cells increased significantly, and there was no significant difference between the two scaffolds (P>0.05). The in vitro cartilage regeneration test indicated that the BMSCs-drug-loaded scaffolds displayed smooth and translucent appearance with yellow color after 6 weeks in vitro culture, and could basically maintained its original shape. The histological and immunohistochemical stainings revealed that the scaffolds displayed typical lacunar structure and cartilage-specific extracellular matrix. In addition, quantitative data revealed that the contents of glycosaminoglycan (GAG) and collagen type Ⅱ were not significantly different from BMSCs-PLGA scaffolds (P>0.05). The evaluation of cartilage regeneration in vivo showed that the BMSCs-drug-loaded scaffolds basically maintained their pre-implantation shape and size at 4 weeks after implantation in goat, while the BMSCs-PLGA scaffolds were severely deformed. The BMSCs-drug-loaded scaffolds had typical cartilage lacuna structure and cartilage specific extracellular matrix, and no obvious inflammatory cells infiltration; while the BMSCs-PLGA scaffolds had a messy fibrous structure, showing obvious inflammatory response. The contents of cartilage-specific GAG and collagen type Ⅱ in BMSCs-drug-loaded scaffolds were significantly higher than those in BMSCs-PLGA scaffolds (P<0.05); the relative gene expressions of IL-1β and TNF-α were significantly lower than those in BMSCs-PLGA scaffolds (P<0.05). ConclusionThe drug-loaded scaffolds have suitable pore size, porosity, cytocompatibility, and good anti-inflammatory properties, and can promote cartilage regeneration after implantation with BMSCs in goats.
ObjectiveTo investigate the expression regulation of inflammation cytokines interleukin 4 (IL-4), IL-6, IL-13, and tumor necrosis factor α (TNF-α) in rats with sciatic nerve defect following olfactory ensheathing cell (OEC) transplantation. MethodsThe primary OEC for cell culture and identification was dissociated from the olfactory bulb of the green fluorescent protein-Sprague Dawley (GFP-SD) rat. One hundred SD rats were randomly divided into 2 groups, and the right sciatic nerve defect (10 mm in length) model was made, then repaired with poly (lactic acid-co-glycolic acid) (PLGA). The mixture of equivalent cultured GFP-OEC and extracellular matrix (ECM) was injected into both ends of PLGA nerve conduit in the experimental group (n=55), and the mixture of DMEM and ECM in the control group (n=45). The general situation of rats was observed after operation. At 6 hours, 1 day, 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, and 6 weeks, the inflammatory cytokines were detected by Western blot. At 2, 4, and 6 weeks, the survival of GFP-OEC was observed in the experimental group. At 9 weeks, HE staining was used to observe the morphology of nerve tissue, and the sensory and motor function and the electrophysiological index were detected. ResultsThe cultured primary cells were GFP-OECs by immunofluorescence staining. Compared with the control group, the experimental group showed significantly increased expression level of IL-4 at 2-6 weeks (P < 0.05), significantly decreased expression level of IL-6 and TNF-α at 3 days and 1 week (P < 0.05) and significantly increased expression level of IL-13 at 1 day and 3-6 weeks (P < 0.05) by Western blot detection. At 2, 4, and 6 weeks, the surviving GFP-OEC of regenerative nerve end was observed in the experimental group under the fluorescence microscope. At 9 weeks, regenerative nerve tissue was loose, and cell morphology was irregular in the experimental group, while the regenerative nerve tissue had vesicular voids and the cell number decreased significantly in the control group. At 9 weeks, the functional recovery of sciatic nerve in the experimental group was better than that of the control group, showing significant difference in the lateral foot retraction time, sciatic nerve function index, muscle action potential latency, and the amplitude of compound muscle action potential (P < 0.05). ConclusionOEC can promote the anti-inflammation cytokines expression of IL-4 and IL-13 and inhibit the pro-inflammatory cytokines expression of IL-6 and TNF-α, which can improve the local inflammatory microenvironment of sciatic nerve and effectively promote the structure and function recovery of sciatic nerve.
ObjectivesTo systematically review the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) on tennis elbow.MethodsPubMed, EMbase, The Cochrane Library, VIP, CNKI and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) on NSAIDs for tennis elbow from inception to May 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 8 RCTs involving 595 patients were included. The results of meta-analysis showed that there were no significant differences in the therapeutic effect between NSAIDs and the placebo group (RR=1.10, 95%CI 0.89 to 1.35, P=0.39) or non-placebo control group (RR=0.88, 95%CI 0.77 to 1.00, P=0.06). Compared with non-placebo control group, NSAIDs group had lower VAS score difference (MD=?1.41, 95%CI ?2.28 to ?0.53, P=0.002).ConclusionsCurrent evidence shows that the effect of NSAIDs on tennis elbow is still uncertain. The improvement of symptoms with NSAIDs may be superior to placebo, but inferior to other treatment methods. Due to the limited quantity and quality of included studies, the above conclusions are required to be verified by more high-quality studies.
ObjectiveTo study the potential protective effects of bone marrow mesenchymal stem cells (BMSCs) on chondrocytes injured by interleukin 1β (IL-1β), and the resistant capacity of chondrocytes when co-cultured indirectly with BMSCs against IL-1β. MethodsSix Sprague Dawley (SD) rats were randomly divided into experimental group (articular cartilage defects) and control group. The content and gene expression of IL-1β were detected at 6 hours after surgical intervention by quantitative real time RCR (qRT-PCR) and ELISA. BMSCs repairing function test: the 18-holes cultured chondrocytes were randomly divided into 3 groups (n=6): cells of blank group were not treated;cells of injured group and co-cultured group were intervened by IL-1β, and Transwell chamber was used to establish co-culture system of BMSCs with chondrocyte in co-cultured group. The mRNA relative expressions of cysteinyl aspartate specific proteinase 3 (Caspase 3), a disintegrin and metalloprotease with Thrombospondin motifs 4 (ADAMTS-4), and ADAMTS-5 were measured via qRT-PCR in chondrocytes, meanwhile Caspase-3 content was detected via ELISA, and the cell apoptosis rate was detected via flow cytometry. BMSCs protecting function test: the 12-holes cultured chondrocytes were randomly divided into 2 groups (n=6), Transwell chamber was used to establish co-culture system of BMSCs with chondrocyte in co-cultured group before the 2 groups were both intervened by IL-1β, then the same detected indexes were taken as the BMSCs repairing function test. ResultsAnimal in vivo studies showed that relative expression of IL-1β mRNA and IL-1β contents were significantly higher in experimental group than control group (P<0.05). BMSCs repair tests showed that mRNA relative expressions of Caspase-3, ADAMTS-4, and ADAMTS-5, Caspase-3 content, and cell apoptosis rate were significantly higher in injured group and co-cultured group than blank group, and in injured group than co-cultured group (P<0.05). BMSCs protect tests showed that mRNA relative expressions of Caspase-3, ADAMTS-4, and ADAMTS-5, Caspase-3 content, and cell apoptosis rate in co-cultured group were significantly lower than those in control group (P<0.05). ConclusionBMSCs, as seed cells for tissue engineering, have potential for applications to anti-inflammation and anti-apoptosis.
ObjectiveTo compare the effect of bromfenac sodium hydrate ophthalmic solution and fluorometholone following sub-bowmans keratomileusis (SBK) from the aspects of subjective visual perception, ophthalmic signs and intraocular pressure. MethodsFifty myopic patients (94 eyes) who underwent SBK from April to May 2013 were divided into two groups according to the different postoperative drug treatment. Patients in group A were treated with bromfenac sodium hydrate (51 eyes), and patients in group B were treated with fluorometholone (43 eyes). To compare the effects of two kinds of drugs after SBK, results of the routine examination were recorded including uncorrected visual acuity (UCVA), refractive status, visual symptoms and signs, intraocular pressure (IOP) and Haze under Corneal Epithelium (HAZE) on pre-operational and postoperative day 1, 7, and 30. ResultsOn the 30th day, IOP in group A and group B were (9.88±2.34) mm Hg (1 mm Hg=0.133 kPa) and (11.00±2.27) mm Hg, respectively, and the difference between the two groups was statistically significant (P<0.05), but there were no statistically significant differences at other time points. There was no statistically significant difference in UCVA, refractive status, visual symptoms and signs, and corneal epithelial staining between the two groups (on day 1, 7, and 30). ConclusionBromfenac sodium and fluorometholone have the same effect in the control of postoperative visual acuity and ophthalmic inflammation. Bromfenac sodium has greater advantages in IOP control. Therefore, bromfenac sodium can substitute fluorometholone in resisting inflammation after SBK.
目的 探討單用和聯用鹽酸氨基葡萄糖與非甾體抗炎藥（NSAID）在椎間盤源性腰痛（DLBP）治療中的有效性。 方法 2011年1月－12月72例DLBP患者，男42例，女30例；年齡22～71歲；體重43～84 kg；病程0.5～10年。通過隨機數字表的方法，將患者分為3組。A組給予鹽酸氨基葡萄糖膠囊750 mg，2次/d，同時給予尼美舒利分散片100 mg，2次/d；B組給予鹽酸氨基葡萄糖膠囊750 mg，2次/d；C組給予尼美舒利分散片100 mg，2次/d。3組均用藥8周后停藥，用藥期間停用其他活血化瘀類藥物及物理治療。選取治療前及治療后第4、8、16周4個時間點，運用疼痛數字評價量表（NRS）、Oswestry功能障礙指數（ODI）、生活質量評價量表SF-36分別對3組患者的腰痛、腰部功能及生活質量進行評價。 結果 63例獲得隨訪，失訪率12.5%。各組患者NRS評分、ODI評分、SF-36評分在治療前后比較差異均有統計學意義（P＜0.05），A組療效明顯優于B、C兩組，B組治療后各項數據較治療前明顯改善（P＜0.05）。 結論 單用鹽酸氨基葡萄糖治療DLBP有效，且在停藥后，仍有一定療效，聯用NSAID效果更佳；遠期療效有待進一步隨訪。
ObjectiveTo systematically review the efficacy and safety of traditional Chinese medicine (TCM) therapies versus non-steroidal anti-inflammatory drugs (NSAIDs) for knee osteoarthritis (KOA). MethodsWe electronically searched databases including PubMed, The Cochrane Library (Issue 5, 2015), EMbase, CNKI, CBM, VIP and WanFang Data from inception to 14 June 2015, to collect randomized controlled trials (RCTs) about TCM therapies for KOA. Two reviewers independently screened literature, extracted data and assessed the methodological quality of included studies. Then network meta-analysis was performed using Stata 12.0 and WinBUGS 1.4.3 softwares. ResultsA total of 56 RCTs involving 7256 patients were included, in which 19 different treatment strategies were investigated. All were short-term efficacy studies. Our work yielded 33 direct and 138 indirect comparisons, among which 76 were demonstrated statistically significant. The result of meta-analysis showed that, the TCM-based therapy group had lower complication rates, compared with the NSAIDs group. TCM internal application+acupuncture+fumigation, internal application+fumigation+moxibustion, acupuncture+massage, TCM extra-apply+massage, massage+fumigation+moxibustion, and massage+fumigation were the top six in terms of treatment effect. NSAIDs ranked 18th. ConclusionThe safety and effectiveness of TCM therapies are generally better than NSAIDs except moxibustion, particularly more remarkable for the top six TCM therapies. TCM comprehensive therapies are superior over mono-modality therapies. Due to the limitation of the present studies, the long-term efficacy of TCM therapies needs further investigation, and our findings also need to be verified by large-scale and well-designed RCTs.