Notes

Micro-Computed Tomography-Based Three-Dimensional Biological Construction of the Place Across the Pterygoid Hamulus.
Cardiac fibrosis is a common pathological manifestation accompanied by various heart diseases, and antifibrotic therapy is an effective strategy to prevent diverse pathological processes of the cardiovascular system. We currently report the pharmacological evaluation of a novel anthraquinone compound (1,8-dihydroxy-6-methyl-9,10-anthraquinone-3-oxy ethyl succinate) named Kanglexin (KLX), as a potent cardioprotective agent with antifibrosis activity. Our results demonstrated that the administration of KLX by intragastric gavage alleviated cardiac dysfunction, hypertrophy, and fibrosis induced by transverse aortic constriction (TAC) surgical operation. Meanwhile, KLX administration relieved endothelial to mesenchymal transition of TAC mice. In TGF β1-treated primary cultured adult mouse cardiac fibroblasts (CFs) and human umbilical vein endothelial cells (HUVECs), KLX inhibited cell proliferation and collagen secretion. Also, KLX suppressed the transformation of fibroblasts to myofibroblasts in CFs. Further studies revealed that KLX-mediated cardiac protection was due to the inhibitory role of TGF-β1/ERK1/2 noncanonical pathway. In summary, our study indicates that KLX attenuated cardiac fibrosis and dysfunction of TAC mice, providing a potentially effective therapeutic strategy for heart pathological remodeling.Several clinical therapies such as tissue repair by replacing injured tissues with functional ones have been reported; however, there is great potential for exploring traditional herbal-induced regeneration with good safety. Tongqiao Huoxue Decoction (TQHXD), a well-known classical traditional Chinese medicinal formula, has been widely used for clinical treatment of stroke. However, biological activity and mechanisms of action of its constituents toward conferring protection against cerebral ischemia-reperfusion (I/R) injury remain unclear. In this present study, we evaluated TQHXD quality using HPLC; then, it was screened for its potential active ingredients using a series of indices, such as their drug-likeness and oral bioavailability. Subsequently, we analyzed the potential mechanisms of TQHXD anti-I/R using gene ontology functional enrichment analyses. The network pharmacological approach enabled us to screen 265 common targets associated with I/R, indicating that TQHXD had remarkable protective effects angiogenesis via the VEGF pathway. Therefore, these results provide proof-of-concept evidence that angiogenesis is a major contributor to TQHXD-treated I/R and that TQHXD is a promising traditional ethnic medicine for the management of this condition.Antiplatelet drugs may increase the risk of gastrointestinal bleeding. Currently, there is no specific score for predicting the risk of gastrointestinal bleeding caused by oral antiplatelet drugs. In this study, the gastrointestinal bleeding risk score was established and compared with the CRUSADE score in order to reduce the occurrence of clinical gastrointestinal bleeding events. Our study included 4052 patients who received oral antiplatelet drugs. Data were obtained from the patient medical records inpatient system. Cases of acute gastrointestinal bleeding and mortality were recorded. The bleeding score was established by logistic regression, area under the receiver operating characteristic curve, and the Hosmer-Lemeshow test. Finally, 171 patients had acute gastrointestinal bleeding. The mortality rates of patients in the bleeding and nonbleeding groups were 24.6 and 4.7%, respectively. A multivariate analysis revealed that an age of >65 years, anemia, recent major bleeding, a history of gastrointestinal bleeding, combined oral anticoagulants, and dual antiplatelet therapy are risk factors, and combined proton pump inhibitors are protective factors for acute gastrointestinal bleeding. We used these risk factors to establish a score for predicting acute gastrointestinal bleeding, named (ABC)2D score. The area under the curve for (ABC)2D score was 0.857 (p less then 0.001), higher than the CRUSADE score of 0.693 (p less then 0.001). The Hosmer-Lemeshow p value was 0.324. We developed the (ABC)2D score based on seven risk factors (i.e., age, anemia, recent major bleeding, a history of gastrointestinal bleeding, no-proton pump inhibitors use, combined oral anticoagulants, and dual antiplatelet therapy). (ABC)2D score was superior to the CRUSADE score. This new risk-scoring model may help to identify patients at a significant risk of gastrointestinal bleeding.Herbaepimedii (HEP), a kidney-tonifying herb, has been commonly used alone or in formula for strengthening kidney function and treating bone disorders. Its bone protective activity has been demonstrated to be via estrogen receptor (ERs). HEP activates the phosphorylation of ERα in an estrogen response element- (ERE-) dependent manner. We examined the bone protective effects of HEP and its potential interactions with Selective Estrogen Receptor Modulators (SERMs, such as tamoxifen and raloxifene) as they act via the same ERs. Six-month-old mature Sprague Dawley sham-operated (Sham) or ovariectomized (OVX) rats were treated with either vehicle, 17ß-estradiol (1.0 mg/kg.day), tamoxifen (Tamo, 1.0 mg/kg.day), raloxifene (Ralo, 3.0 mg/kg.day), HEP (0.16 g/kg.day), or its combinations with respective SERMs (HEP + Tamo; HEP + Ralo) for 12 weeks. HEP and SERMs as well as their combinations significantly restored changes in bone mineral density (BMD), trabecular bone properties, and bone turnover biomarkers induced by ovarian sex hormone deficiency in ovariectomized rats. Besides the increase in serum estradiol, inhibition on follicle stimulating hormone (FSH) might also be involved in the osteoprotective activities of HEP and SERMs. HEP interacted with SERMs to protect bones from ovarian sex hormone deficiency without altering SERMs' bone protective activities. HEP neither induced changes in uterus weight nor altered the uterotrophic activity of SERMs in OVX rats. In human osteosarcoma MG-63 cells, HEP-treated serum (HEP-Ts) significantly promoted alkaline phosphatase (ALP) activity like the crude HEP extract did but did not stimulate ERE activity. Our study also reported that biologically activated HEP interacted with SERMs to promote ALP activity without altering the action of SERMs at most of the concentrations tested in MG-63 cells. HEP exerted bone protective activity and the use of HEP did not alter the bone protective activities of SERMs when they were used simultaneously in an estrogen-deficient rat model.Chronic heart failure (CHF) is a common cardiovascular disease with high mortality and a poor prognosis, which places heavy burdens upon society and families. Traditional Chinese medicine (TCM) has been used extensively as complementary treatment for CHF. Guanxinshutong (GXST) capsules are used commonly for the treatment of coronary heart disease (CHD). Experimental research and small-sample clinical trials have shown that GXST can attenuate CHF. However, the effects of GXST as complementary medicine in CHF treatment lack high-quality clinical evidence. We have designed a multicenter, randomized, double-blind, placebo-controlled clinical trial that explores the efficacy and safety of using GXST compared with placebo for patients with CHF with reduced left ventricular ejection fraction (LVEF). A total of 480 participants will be assigned randomly to the GXST group or placebo group at a 21 ratio. GXST and placebo will be added to standard treatment for 12 weeks, and then followed up for another 40 weeks. The primary outcome is the improvement value of 6-min walk distance, and the secondary outcomes include plasma levels of N-terminal pro-B-type natriuretic peptide, New York Heart Association classification, Minnesota Living with Heart Failure Questionnaire scores, echocardiographic parameters, and clinical endpoint events. Adverse events will be monitored throughout the trial. Data will be analyzed following a predefined statistical analysis plan. This study will show the effects of the specific use of GXST in CHF patients with reduced LVEF. The Research Ethics Committee of the Second Affiliated Hospital of Zhejiang Chinese Medical University has approved this study (2019-Y-003-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1900023877). Our results will be disseminated to the public through peer-reviewed journals, academic conferences, and the Internet.Aim To summarize the evidence on the performance of artificial intelligence vs. KPT-185 solubility dmso traditional pharmacoepidemiological techniques. Methods Ovid MEDLINE (01/1950 to 05/2019) was searched to identify observational studies, meta-analyses, and clinical trials using artificial intelligence techniques having a drug as the exposure or the outcome of the study. Only studies with an available full text in the English language were evaluated. Results In all, 72 original articles and five reviews were identified via Ovid MEDLINE of which 19 (26.4%) compared the performance of artificial intelligence techniques with traditional pharmacoepidemiological methods. In total, 44 comparisons have been performed in articles that aimed at 1) predicting the needed dosage given the patient's characteristics (31.8%), 2) predicting the clinical response following a pharmacological treatment (29.5%), 3) predicting the occurrence/severity of adverse drug reactions (20.5%), 4) predicting the propensity score (9.1%), 5) identifying subpopulation more at risk of drug inefficacy (4.5%), 6) predicting drug consumption (2.3%), and 7) predicting drug-induced lengths of stay in hospital (2.3%). In 22 out of 44 (50.0%) comparisons, artificial intelligence performed better than traditional pharmacoepidemiological techniques. Random forest (seven out of 11 comparisons; 63.6%) and artificial neural network (six out of 10 comparisons; 60.0%) were the techniques that in most of the comparisons outperformed traditional pharmacoepidemiological methods. Conclusion Only a small fraction of articles compared the performance of artificial intelligence techniques with traditional pharmacoepidemiological methods and not all artificial intelligence techniques have been compared in a Pharmacoepidemiological setting. However, in 50% of comparisons, artificial intelligence performed better than pharmacoepidemiological techniques.PurposeN6-methyladenosine (m6A) mRNA methylation is affected by dietary factors and associated with lipid metabolism; however, whether the regulatory role of resveratrol in lipid metabolism is involved in m6A mRNA methylation remains unknown. Here, the objective of this study was to investigate the effect of resveratrol on hepatic lipid metabolism and m6A RNA methylation in the liver of mice. Methods A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group). Final body weight of mice was measured before sacrificing. Perirhemtric fat, abdominal and epididymal fat, liver tissues, and serum were collected at sacrifice and analyzed. Briefly, mice phenotype, lipid metabolic index, and m6A modification in the liver were assessed. Results Compared to the HFD group, dietary resveratrol supplementation reduced the body weight and relative abdominal, epididymal, and perirhemtric fat weight in high-fat-exposed mice; however, resveratrol significantly increased average daily feed intake in mice given HFD.
Read More: https://www.selleckchem.com/products/kpt-185.html