Background: Baiyu Decoction (BYD), a clinical prescription of traditional Chinese medicine, has been proven to be valuable for treating ulcerative colitis (UC) by enema. However, the mechanism of BYD ...against UC remains unclear. Purpose: A combination of bio informatics methods including network pharmacology and molecular docking and animal experiments were utilized to investigate the potential mechanism of BYD in the treatment of UC. Materials and Methods: Firstly, the representative compounds of each herb in BYD were detected by liquid chromatography-mass spectrometry. Subsequently, we predicted the core targets and potential pathways of BYD for treating UC through network pharmacology. And rat colitis model was established with dextran sodium sulfate. UC rats were subjected to BYD enema administration, during which we recorded body weight changes, disease activity index, and colon length to assess the effectiveness of BYD. Besides, quantitative real-time PCR, western blotting, ELISA and immunofluorescence were used to detect intestinal inflammatory factors, intestinal barrier biomarkers and TOLL-like receptor pathway in rats. Finally, the core components and targets of BYD were subjected to molecular docking so as to further validate the results of network pharmacology. Results: A total of 41 active compositions and 203 targets related to BYD-UC were subjected to screening. The results of bioinformatics analysis showed that quercetin and kaempferol may be the main compounds. Additionally, AKT1, IL-6, TP53, TNF and IL-1beta were regarded as potential therapeutic targets. KEGG results explained that TOLL-like receptor pathway might play a pivotal role in BYD protecting against UC. In addition, animal experiments and molecular docking validated the network pharmacology results. BYD enema treatment can reduce body weight loss, lower disease activity index score, reverse colon shortening, relieve intestinal inflammation, protect intestinal barrier, and inhibit TOLL-like receptor pathway in UC rats. Besides, molecular docking suggested that quercetin and kaempferol docked well with TLR4, AKT1, IL-6, TP53. Conclusion: Utilizing network pharmacology, animal studies, and molecular docking, enema therapy with BYD was confirmed to have anti-UC efficacy by alleviating intestinal inflammation, protecting the intestinal barrier, and inhibiting the TOLL-like receptor pathway. Researchers should focus not only on oral medications but also on the rectal administration of medications in furtherance of the cure of ulcerative colitis. Keywords: network pharmacology, ulcerative colitis, enema therapy, TLR4/MyD88/NF-KB pathway
Identification of risk factors for dementia after stroke is best performed in comparison with stroke-free controls, because older subjects at high risk for stroke also have a substantial risk of ...dementia in the absence of stroke. Previous case-control studies were hospital-based. We used a nested case-control design to prospectively evaluate these risk factors in the community-based Framingham Study cohort.
We compared 212 subjects who were free of dementia in January 1982 and sustained a first stroke after this date, with 1060 age- and sex-matched, stroke- and dementia-free controls. We calculated 10-year risks of dementia (by Diagnostic and Statistical Manual of Mental Disorders, Volume IV criteria) developing in cases and controls and also estimated the hazard ratios within subgroups defined by exposure to various demographic factors (age, gender, education), stroke-related features (right or left hemisphere, stroke type, second stroke), stroke risk factors (hypertension, diabetes, atrial fibrillation, smoking) and apolipoprotein E genotype.
Dementia developed in 19.3% of cases and 11.0% of controls. Baseline stroke doubled the risk of dementia (hazard ratio HR: 2.0; 95% confidence interval CI: 1.5 to 3.1) and adjustment for age, sex, education, and exposure to individual stroke risk factors did not diminish the risk (HR: 2.4; 95% CI: 1.6 to 3.7). The HR was higher in younger subjects (age younger than 80 years HR: 2.6; 95% CI: 1.5 to 4.5), apolipoprotein E 3/3 homozygotes (HR: 3.4; 95% CI: 2.0 to 5.8), and high school graduates (HR: 2.4; 95% CI: 1.5 to 3.9).
Stroke increases a subject's risk of dementia as compared with age- and sex-matched controls. Primary and secondary prevention of stroke should significantly decrease the risk of all dementia.
Cerebral microbleeds (CMBs) are areas of low signal intensity on gradient echo T2*-weighted magnetic resonance imaging (T2*MRI) corresponding to hemosiderin deposits in the perivascular space. ...Microangiopathy from atherosclerosis or amyloid angiopathy might lead to the formation of these lesions; therefore, there may be associations between CMBs and cardiovascular risk factors, APOE allele status, and brain morphology. We examined these relationships in the Framingham Study (FHS).
In 472 subjects from the FHS Offspring and Cohort, we related CMB status to age, sex, systolic blood pressure, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels, smoking, diabetes, total hemispheric brain volume, white matter hyperintensity volume (WMHV), and APOE allele status.
Overall prevalence of CMBs was 4.7%, but CMBs were more prevalent with advanced age and male sex. Blood pressure, brain volume, and WMHV were related to CMBs in crude analysis but not after adjustment for age and sex. There were no significant relationships demonstrated between CMBs and APOE allele status, cholesterol, smoking, or diabetes.
There is a low prevalence of CMBs in the community and a strong relationship with increasing age and male sex. We found no independent relationships with cardiovascular risk factors, APOE status, brain volumes, or WMH.
Introduction
This study examined plasma glial fibrillary acidic protein (GFAP) as a biomarker of cognitive impairment due to Alzheimer's disease (AD) with and against plasma neurofilament light chain ...(NfL), and phosphorylated tau (p‐tau)181+231.
Methods
Plasma samples were analyzed using Simoa platform for 567 participants spanning the AD continuum. Cognitive diagnosis, neuropsychological testing, and dementia severity were examined for cross‐sectional and longitudinal outcomes.
Results
Plasma GFAP discriminated AD dementia from normal cognition (adjusted mean difference = 0.90 standard deviation SD) and mild cognitive impairment (adjusted mean difference = 0.72 SD), and demonstrated superior discrimination compared to alternative plasma biomarkers. Higher GFAP was associated with worse dementia severity and worse performance on 11 of 12 neuropsychological tests. Longitudinally, GFAP predicted decline in memory, but did not predict conversion to mild cognitive impairment or dementia.
Discussion
Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel to detect in vivo AD.
In today’s competitive fashion retailing business, providing “mix-and-match” or “fashion coordination” recommendations can enhance customer service, brand loyalty and improve sales. In this study, we ...propose a decision support tool for fashion coordination through the integration of the knowledge-based attribute evaluation expert system and the Takagi–Sugeno fuzzy neural network (TSFNN). A set of attributes of the apparel items for coordination are identified and formulated. The evaluation of these attributes can be accomplished by a knowledge-based expert system which can handle the difficulty of processing linguistic and categorical information effectively. A fuzzy clustering technique and a new hybrid learning algorithm combining the PSO and GA techniques are proposed to reduce the coordination rules and the training time for the TSFNN. The experimental results show that rules reduction can shorten the TSFNN training time while keeping a very satisfactory and low MSE value. The proposed hybrid algorithm outperforms the Back Propagation, the Genetic Algorithm, and the Particle Swarm Optimization. The apparel pairs recommended by the decision support tool are now integrated with a smart dressing system of a fashion retailing company in Hong Kong and practically used.
Considering the single-agent activity of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and doxorubicin in breast cancer and their potential non-cross-resistance, several ...docetaxel/anthracycline-based combination chemotherapies were developed in phase I and II programs for metastatic breast cancer patients. The rationale for these combinations was also reinforced by the fact that docetaxel showed significant activity in phase III trials in patients previously exposed or having failed anthracycline chemotherapy. In a pivotal randomized phase III study of doxorubicin plus docetaxel versus doxorubicin plus cyclophosphamide as first-line chemotherapy for 429 patients with metastatic breast cancer, doxorubicin/docetaxel emerged as the more effective regimen. Despite a lower-dose intensity of doxorubicin, patients receiving doxorubicin/docetaxel experienced a higher response rate as well as a significantly longer time to progression and time to treatment failure. This difference was seen even in patients with poor-prognosis disease. Febrile neutropenia was more common in doxorubicin/docetaxel-treated patients. However, there were no septic deaths among 213 patients receiving doxorubicin/ docetaxel. Extrahematologic toxicity appeared mild for both regimens and the combination docetaxel/doxorubicin did not increase the cardiac toxicity expected for an anthracycline-containing regimen. Docetaxel plus doxorubicin is the first regimen, involving a newly developed agent, proven superior to a standard anthracycline-containing combination in metastatic breast cancer and its potential is now being investigated in the adjuvant setting.
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