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11.
In this study, we examined the therapeutic effects of an immune-stimulating peptide, WKYMVm, in ulcerative colitis. The administration of WKYMVm to dextran sodium sulfate (DSS)-treated mice reversed decreases in body weight, bleeding score and stool score in addition to reversing DSS-induced mucosa destruction and shortened colon. The WKYMVm-induced therapeutic effect against ulcerative colitis was strongly inhibited by a formyl peptide receptor (FPR) 2 antagonist, WRWWWW, indicating the crucial role of FPR2 in this effect. Mechanistically, WKYMVm effectively decreases intestinal permeability by stimulating colon epithelial cell proliferation. WKYMVm also strongly decreases interleukin-23 and transforming growth factor-β production in the colon of DSS-treated mice. We suggest that the potent immune-modulating peptide WKYMVm and its receptor FPR2 may be useful in the development of efficient therapeutic agents against chronic intestinal inflammatory diseases.  相似文献   
12.
    
In this study, infrared spectroscopy, high-performance liquid chromatography, and matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) technology were applied to systematically explain the Schisandra chinensis’s polysaccharide transformation in configuration, molecular weight, monosaccharide composition, and anti-ulcerative colitis (UC) activity after vinegar processing. Scanning electron microscopic results showed that the appearance of S. chinensis polysaccharide changed significantly after steaming with vinegar. The MALDI-TOF-MS results showed that the mass spectra of raw S. chinensis polysaccharides (RSCP) were slightly lower than those of vinegar-processed S. chinensis polysaccharides (VSCP). The RSCP showed higher peaks at m/z 1350.790, 2016.796, and 2665.985, all with left-skewed distribution, and the molecular weights were concentrated in the range of 1300–3100, with no higher peak above m/z 5000. The VSCPs showed a whole band below m/z 3000, with m/z 1021.096 being the highest peak, and the intensity decreased with the increase of m/z. In addition, compared to RSCPs, VSCPs can significantly increase the content of intestinal short-chain fatty acids (SCFAs). This study showed that the apparent morphology and molecular weight of S. chinensis’s polysaccharides significantly changed after steaming with vinegar. These changes directly affect its anti-UC effect significantly, and its mechanism is closely related to improving the structure and diversity of gut microbiota and SCFA metabolism.  相似文献   
13.
    
Ulcerative colitis is a chronic inflammatory bowel disorder that is hard to cure once diagnosed. Bisdemethoxycurcumin has shown positive effects on inflammatory diseases. However, the underlying bioactive interaction between bisdemethoxycurcumin and ulcerative colitis is unclear. The objective of this study was to determine the core target and potential mechanism of action of bisdemethoxycurcumin as a therapy for ulcerative colitis. The public databases were used to identify potential targets for bisdemethoxycurcumin and ulcerative colitis. To investigate the potential mechanisms, the protein-protein interaction network, gene ontology analysis, and Kyoto encyclopedia of genes and genomes analysis have been carried out. Subsequently, experimental verification was conducted to confirm the findings. A total of 132 intersecting genes of bisdemethoxycurcumin, as well as ulcerative coli-tis-related targets, were obtained. SRC, EGFR, AKT1, and PIK3R1 were the targets of highest potential, and the PI3K/Akt and MAPK pathways may be essential for the treatment of ulcerative colitis by bisdemethoxycurcumin. Molecular docking demonstrated that bisdemethoxycurcumin combined well with SRC, EGFR, PIK3R1, and AKT1. Moreover, the in vitro experiments suggested that bisdemethoxycurcumin might reduce LPS-induced pro-inflammatory cytokines levels in RAW264.7 cells by suppressing PI3K/Akt and MAPK pathways. Our study provided a comprehensive overview of the potential targets and molecular mechanism of bisdemethoxycurcumin against ulcerative colitis. Furthermore, it also provided a theoretical basis for the clinical treatment of ulcerative colitis, as well as compelling evidence for further study on the mechanism of bisdemethoxycurcumin in the treatment of ulcerative colitis.  相似文献   
14.
    
Combination therapy through colon-targeted oral delivery of multiple drugs presents a promising approach for effectively treating ulcerative colitis (UC). However, the codelivery of drugs with diverse physicochemical properties in a single formulation remains a formidable challenge. Here, microcapsules are designed based on hydroxyethyl starch–curcumin (HES─CUR) conjugates to enable the simultaneous delivery of hydrophobic dexamethasone acetate (DA) and hydrophilic cefazolin sodium (CS), yielding multiple drug-loaded microcapsules (CS/DA-loaded HES─CUR microcapsules, CDHC-MCs) tailored for colon-targeted therapy of UC. Thorough characterization confirms the successful synthesis and exceptional biocompatibility of CDHC-MCs. Biodistribution studies demonstrate that the microcapsules exhibit an impressive inflammatory targeting effect, accumulating preferentially in inflamed colons. In vivo experiments employing a dextran-sulfate-sodium-induced UC mouse model reveal that CDHC-MCs not only arrest UC progression but also facilitate the restoration of colon length and alleviate inflammation-related splenomegaly. These findings highlight the potential of colon-targeted delivery of multiple drugs within a single formulation as a promising strategy to enhance UC treatment, and the CDHC-MCs developed in this study hold great potential in developing novel oral formulations for advanced UC therapy.  相似文献   
15.
    
Ginseng is a vastly used herbal supplement in Southeast Asian countries. Red ginseng extract enriched with Rg3 (Rg3-RGE) is a formula that has been extensively studied owing to its various biological properties. Persicaria tinctoria (PT), belonging to the Polygonaceae family, has also been reported for its anti-inflammatory properties. Ulcerative colitis (UC) is inflammation of the large intestine, particularly in the colon. This disease is increasingly common and has high probability of relapse. We investigated, separately and in combination, the effects of Rg3-RGE and PT using murine exemplary of UC induced by DSS (Dextran Sulfate Sodium). For in vitro and in vivo experiments, nitric oxide assay, qRT-Polymerase Chain Reaction (PCR), Western blot, ulcerative colitis introduced by DSS, Enzyme Linked Immunosorbent Assay (ELISA), and flow cytometry analysis were performed. The results obtained demonstrate that treatment with Rg3-RGE + PT showed synergism to suppress inflammation (in vitro) in RAW 264.7 cells via mitogen-activated protein kinase and nuclear factor κB pathways. Moreover, in C57BL/6 mice, this mixture exhibits strong anti-inflammatory effects in restoring colon length, histopathological damage, pro-inflammatory mediators, and cytokines amount, and decreasing levels of NLRP3 inflammasome (in vivo). Our results recommend that this mixture can be used for the prevention of UC as a prophylactic/therapeutic supplement.  相似文献   
16.
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Ulcerative colitis, an inflammatory bowel disease, is a chronic inflammatory disorder that results in ulcers of the colon and rectum without known etiology.Ulcerative colitis causes a huge public health care burden particularly in developed countries.Many studies suggest that ulcerative colitis results from an abnormal immune response against components of commensal microbiota in genetically susceptible individuals.However, understanding of the disease mechanisms at cellular and molecular levels remains largely elusive.In this paper, a network model is developed based on our previous study and computer simulations are performed using an agent-based network modeling to elucidate the dynamics of immune response in ulcerative colitis progression.Our modeling study identifies several important positive feedback loops as a driving force for ulcerative colitis initiation and progression.The results demonstrate that although immune response in ulcerative colitis patients is dominated by anti-inflammatory/regulatory cells such as alternatively activated macrophages and type Ⅱ natural killer T cells, proinflammatory cells including classically activated macrophages, T helper 1 and T helper 17 cells, and their secreted cytokines tumor necrosis factor-α, interleukin-12, interleukin-23, interleukin-17 and interferon-γ remain at certain levels (lower than those in Crohn's disease, another inflammatory bowel disease).Long-term exposure to these proinflammatory components, causes mucosal tissue damage persistently, leading to ulcerative colitis.Our simulation results are qualitatively in agreement with clinical and laboratory measurements, offering novel insight into the disease mechanisms.  相似文献   
17.
(Poly)phenols (PPs) may have a therapeutic benefit in gastrointestinal (GI) disorders, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). The aim of this review is to summarise the evidence-base in this regard. Observational evidence does not give a clear indication that PP intake has a preventative role for IBD or IBS, while interventional studies suggest these compounds may confer symptomatic and health-related quality of life improvements in known patients. There are inconsistent results for effects on markers of inflammation, but there are promising reports of endoscopic improvement. Work on the effects of PPs on intestinal permeability and oxidative stress is limited and therefore conclusions cannot be formed. Future work on the use of PPs in IBD and IBS will strengthen the understanding of clinical and mechanistic effects.  相似文献   
18.
Abstract

The anti-inflammatory activities of fucoxanthin, a marine carotenoid derived from the macroalgae and microalgae, have been demonstrated in the previous studies. However, the effect of fucoxanthin on ulcerative colitis (UC), an inflammatory bowel disease, was still unclear. In this study, we evaluated the in vivo anti-inflammatory effect of fucoxanthin on dextran sulfate sodium(DSS)-induced colitis in mice. Fucoxanthin at the doses of 50 and 100?mg/kg/day significantly protected against DSS-induced gradual loss of body weight, exhibited inhibitory effects on the DSS-induced increase of disease activity index and colon shortening. Moreover, fucoxanthin treatment resulted in a marked amelioration of the histological damage in the colon, and reduced the colonic PGE2 levels in colitic mice. In addition, the DSS-induced overexpressions of inflammation-related molecules including COX‐2 and NF-κB were significantly decreased in fucoxanthin-treated mice. These finding suggested that the use of fucoxanthin provides a new and attractive alternative to control UC.  相似文献   
19.
Metabolism of the colonic mucosa of patients with ulcerative colitis (UC; n=31) and Crohn's disease (CD; n=26) and normal mucosa (control, n=26) was investigated using in vitro high-resolution proton magnetic resonance spectroscopy. Of the 31 UC patients, 20 were in the active phase and 11 were in the remission phase of the disease. Out of 26 CD patients, 20 were in the active phase, while 6 were in the remission phase of the disease. Twenty-nine metabolites were assigned unambiguously in the perchloric acid extract of colonic mucosa. In the active phase of UC and CD, significantly lower (P相似文献   
20.

Background

The histological extent of inflammatory bowel disease (IBD) is greater than that evident by colonoscopic evaluation. We hypothesized that metabolic profile in macroscopically un-involved colonic mucosa in IBD is similar to that of controls with healthy colon. We thus assessed the differences in metabolic profile in macroscopically involved and un-involved colonic mucosa of IBD patients to further substantiate the extent of disease.

Patients and Methods

Colonic mucosal biopsies were obtained and snap frozen from both the macroscopically un-involved and involved colonic mucosa of IBD patients and macroscopically normal colonic mucosa of controls and were subjected to in-vitro high-resolution proton (1H) magnetic resonance (MR) spectroscopy and the concentrations of metabolites were determined.

Results

Thirty-two metabolites were assigned in the proton MR spectrum of colonic mucosa of IBD patients. The concentrations of amino acids (isoleucine, leucine, valine, arginine, lysine, glutamine/glutamate, alanine), membrane metabolites (choline, glycerophosphorylcholine/phosphorylcholine), glycolytic product (lactate) and short chain fatty acid (formate) were significantly lower while significantly high level of glucose were observed in the macroscopically un-involved colonic mucosa of IBD patients compared to the macroscopically normal mucosa of controls. There was no significant difference in the concentrations of metabolites in macroscopically involved and un-involved colonic mucosa of IBD patients.

Conclusions

The metabolic profile in macroscopically un-involved colonic mucosa of IBD patients is similar to that of macroscopically involved mucosa but different from colonic mucosa of controls. This suggests that even macroscopically un-involved colonic mucosa is metabolically abnormal and may explain the increase in extent of disease with time.  相似文献   
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