Objective To investigate the medication advancement of gastrointestinal polyposis in patients with Peutz-Jeghers syndrome (PJS). Methods Literatures about the medication advancement on gastrointestinal polyposis of PJS were reviewed and analyzed. The recent development of targeting drugs, especially the data of cyclooxygenase-2 selective inhibitors and rapamycin, were emphatically summarized. Results With the deep investigation of PJS and application of selective drugs, the medication of gastrointestinal polyposis in cases of PJS has got more advancement. The extensive use of synthetic cyclooxygenase-2 inhibitors and rapamycin in clinic developed a new way to treat gastrointestinal polyposis of PJS. Conclusion The cyclooxygenase-2 selective inhibitors and rapamycin have the following features: noninvasive, high selectivity and good curative effects. They have splendid prospects in the clinical treatment of gastrointestinal polyposis in patients with PJS and are bring the treatment of gastrointestinal polyposis in cases of PJS into a targeting therapy phase.
Objective To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then investigate its physicochemical characteristics and in vitro and in vivo biological properties. Methods Using sulfhydryl POSS (POSS-SH) as a nano-construction platform, polyethylene glycol and DS were chemically linked through the “click chemistry” method to construct functional nanoparticle POSS-DS. The composition was analyzed by nuclear magnetic resonance spectroscopy and the morphology was characterized by transmission electron microscopy. In order to achieve drug sustained release, POSS-DS was encapsulated in HAMA, and hybrid hydrogel microspheres were prepared by microfluidic technology, namely HAMA@POSS-DS. The morphology of the hybrid hydrogel microspheres was characterized by optical microscope and scanning electron microscope. The in vitro degradation and drug release efficiency were observed. Cell counting kit 8 (CCK-8) and live/dead staining were used to detect the effect on chondrocyte proliferation. Moreover, a chondrocyte inflammation model was constructed and cultured with HAMA@POSS-DS. The relevant inflammatory indicators, including collagen type Ⅱ, aggrecan (AGG), matrix metalloproteinase 13 (MMP-13), recombinant A disintegrin and metalloproteinase with thrombospondin 5 (Adamts5), and recombinant tachykinin precursor 1 (TAC1) were detected by immunofluorescence staining and real-time fluorescence quantitative PCR, with normal cultured chondrocytes and the chondrocyte inflammation model without treatment as control group and blank group respectively to further evaluate their anti-inflammatory activity. Finally, by constructing a rat model of knee osteoarthritis, the effectiveness of HAMA@POSS-DS on osteoarthritis was evaluated by X-ray film and Micro-CT examination. Results The overall particle size of POSS-DS nanoparticles was uniform with a diameter of about 100 nm. HAMA@POSS-DS hydrogel microspheres were opaque spheres with a diameter of about 100 μm and a spherical porous structure. The degradation period was 9 weeks, during which the loaded POSS-DS nanoparticles were slowly released. CCK-8 and live/dead staining showed no obvious cytotoxicity at HAMA@POSS-DS, and POSS-DS released by HAMA@POSS-DS significantly promoted cell proliferation (P<0.05). In the chondrocyte anti-inflammatory experiment, the relative expression of collagen type Ⅱ mRNA in HAMA@POSS-DS group was significantly higher than that in control group and blank group (P<0.05). The relative expression level of AGG mRNA was significantly higher than that of blank group (P<0.05). The relative expressions of MMP-13, Adamts5, and TAC1 mRNA in HAMA@POSS-DS group were significantly lower than those in blank group (P<0.05). In vivo experiments showed that the joint space width decreased after operation in rats with osteoarthritis, but HAMA@POSS-DS delayed the process of joint space narrowing and significantly improved the periarticular osteophytosis (P<0.05). Conclusion HAMA@POSS-DS can effectively regulate the local inflammatory microenvironment and significantly promote chondrocyte proliferation, which is conducive to promoting cartilage regeneration and repair in osteoarthritis.
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.
Objective To improve the knowledge of epidemiology, diagnosis and treatment of aspirin induced asthma ( AIA) in China. Methods Thirty-six cases with AIA who were reported in 30 papers in recent 10 years were analyzed retrospectively. Results The drugs which induced AIA in China mainly included acetylsalicylic acid ( aspirin) , ibuprofen ( Fenbid, ibuprofen) , while acetaminophen ( paracetamol,Bufferin, Tylenol ) , phenylpropanoid thiazide ( Piroxicam) , methoxy-naphthalene C acid ( naproxen) ,diclofenac in rare cases. 28. 6% ( 8 /28) of AIA patients were complicated with nasal disease . AIA could occur at all ages, especially for those over 40 years ( 72. 2% , 26 /36) . No significant difference of prevalencein male and female. The onset time of AIA was less than 60min in 71. 4% and gt;120min in 38. 6% . Most patients took the medications by oral ( 83. 3% ,30/36) , but the AIA onset time was not different by different administration route. Conclusions The incidence of AIA increases in recent years because of widely use of NSAIDs. However, no awareness of NSAIDs induced asthma is common in patients and physicians. For asthma patients it must be caution to take antipyretic analgesic anti-inflammatory drugs. If necessary,methoxy-naphthalene C acid ( naproxen) and diclofenac could be better choice.
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.
Sepsis is a worldwide problem. Although there are many related researchs and animal experiments about sepsis, the mortality of sepsis is still high. In the early stage of sepsis, after the pathogenic bacteria invade the body, the immune response produced by the body promotes the synthesis and secretion of a series of cytokines. Among them, there are proinflammatory cytokines that promote inflammatory response and anti-inflammatory cytokines that inhibit inflammatory response. These cytokines interact with each other and maintain a dynamic balance in complex cell grid. This is to restore the steady state of the body after resisting and eliminating the invaders.Anti-inflammatory cytokines play an important role in it. They act on specific immune cells or immune regulatory receptors. Anti-inflammatory cytokines limit persistent or excessive inflammatory responses after killing invaders, and reduce or block pro-inflammatory cytokine activities. These anti-inflammatory cytokines also can heal body to restore the normal immune physiological level of the organism. This article will review the related research of anti-inflammatory cytokines in sepsis.
ObjectivesTo systematically review the risk factors for intestinal injury induced by non-steroidal anti-inflammatory drugs(NSAIDs).MethodsWe comprehensively searched WanFang Data, CNKI, Web of Science, EBSCO, PubMed and The Cochrane Library databases to collect studies on risk factors of NSAIDs-induced intestinal injury. Two reviewers independently screened literature, extracted data and assessed risk of bias, and then, meta-analysis was performed by using RevMan 5.2 and STATA 12.0 software.ResultsA total of 6 case-control studies were included, in which 265 patients were in the case group and 301 patients in the control group. The results of meta-analysis showed that PPI was an independent risk factor for NSAIDs-induced intestinal injury (OR=1.59, 95%CI 1.07 to 2.35, P=0.02). In addition, patients with osteoarthritis (OR=2.44, 95% CI 1.11 to 5.36, P=0.03) or rheumatoid arthritis (OR=3.04, 95% CI 1.31 to 7.03, P=0.01) was associated with intestinal mucosal injury induced by NSAIDs. Gender, age, smoking history, drinking history, H2RA and rebamipide medication history, cardiovascular disease and cerebrovascular disease were not associated with intestinal injury.ConclusionsPPI is an independent risk factor for NSAIDs-induced intestinal injury. However, studies with high-quality, larger sample size are required to further verify that PPI increases the prevalence of intestinal injury.