Michelsenmedeiros2766

Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. Stroke is a disease with high prevalence and incidence, the pathogenesis is a complex cascade reaction. In recent years, it's reported that a vast number of natural products have demonstrated beneficial effects on stroke worldwide. Natural products have been discovered to modulate activities with multiple targets and signaling pathways to exert neuroprotection via direct or indirect effects on enzymes, such as kinases, regulatory receptors, and proteins. This review provides a comprehensive summary of the established pharmacological effects and multiple target mechanisms of natural products for cerebral ischemic injury in vitro and in vivo preclinical models, and their potential neuro-therapeutic applications. In addition, the biological activity of natural products is closely related to their structure, and the structure-activity relationship of most natural products in neuroprotection is lacking, which should be further explored in future. GSK'872 mouse Overall, we stress on natural products for their role in neuroprotection, and this wide band of pharmacological or biological activities has made them suitable candidates for the treatment of stroke.Statins can cause muscle symptoms resulting in poor adherence to therapy and increased cardiovascular risk. We hypothesize that combinations of potentially functional SNPs (pfSNPs), rather than individual SNPs, better predict myalgia in patients on atorvastatin. This study assesses the value of potentially functional single nucleotide polymorphisms (pfSNPs) and employs six machine learning algorithms to identify the combination of SNPs that best predict myalgia. Methods Whole genome sequencing of 183 Chinese, Malay and Indian patients from Singapore was conducted to identify genetic variants associated with atorvastatin induced myalgia. To adjust for confounding factors, demographic and clinical characteristics were also examined for their association with myalgia. The top factor, sex, was then used as a covariate in the whole genome association analyses. link2 Variants that were highly associated with myalgia from this and previous studies were extracted, assessed for potential functionality (pfSNPs) and incorporathe majority of machine learning models tested. Conclusion Combinations of pfSNPs that were consistently identified by different machine learning models to have high predictive performance have good potential to be clinically useful for predicting atorvastatin-induced myalgia once validated against an independent cohort of patients.Andrographolide (Andro) has known to treat various illnesses such as colds, diarrhea, fever and infectious diseases. However, the effect mechanism of Andro is still unclear. Therefore, we used high-throughput metabolomics analysis to discover biomarkers, metabolic profiles and pathways to reveal the pharmacological action and effective mechanism of Andro against lung cancer. The metabolic effects of Andro on lung cancer animal was explored by ultra-performance liquid chromatography-triple-time of flight/mass spectrometry (UPLC-TOF/MS) analysis. Our results showed that Andro exhibited significant protective effects against lung cancer. Compared with control group, a total of 25 metabolites biomarkers was identified in urine of model animals, which 18 of them were regulated toward the normal direction after Andro treatment, and network pharmacology analysis showed that they were related with 570 proteins. Biological pathways analysis showed that the 11 metabolism pathways were regulated by Andro treatment in lung cancer mouse, and amino acid metabolism and arachidonic acid metabolism have great potential as target pathways for Andro against lung cancer. It revealed that high-throughput metabolomics combined with network pharmacology analysis provides deeply insight into the therapeutic mechanisms of natural product for promoting medicine development and disease treatment.Dichroa alkali salt (DAS) is the active ingredient of Changshan, a traditional Chinese antimalarial medicine. However, owing to its vomiting side effects, its clinical use is limited. Recently, DAS-induced vomiting has attracted broad attention; however, the mechanisms involved have not yet been elucidated. The present study aimed to explore DAS induced vomiting and decipher the potential role of the 5-serotonin (5-HT) and substance p (SP) signaling pathways. We used a combination of approaches in the context of a rat pica model, such as immunoblot analysis, HPLC-ECD, ELISA, quantitative real-time PCR, pharmacological inhibition, and immunohistochemistry assays. We demonstrated that DAS contributed to Changshan-induced vomiting via the activation of the 5-HT and SP signaling pathways. DAS could induce a dose-dependent kaolin intake in the rat pica model. Moreover, DAS caused a similar profile as Cisplatin (DDP) "low-dose double-peak, high-dose single-peak pica phenomenon". Interestingly, treatment with DAS stimulated the peripheral ileum and central medulla oblongata and augmented the release of 5-HT, SP, and preprotachykinin-A and the expression of 5-HT3 and NK1 receptors in the two issues in acute phase. Additionally, the 5-HT3 and NK1 receptor antagonists effectively alleviated DAS-induced kaolin intake and significantly reduced DAS-induced 5-HT and SP levels in the two issues in acute phase. Similar responses were not observed in the context of dopamine receptor inhibition. This study innovatively revealed that the 5-HT and SP-mediated vomiting network plays an important role in DAS-induced acute vomiting; of note, ondansetron, and aprepitant can effectively antagonize DAS-induced vomiting. Our results suggest a potential therapeutic strategy (based on drugs approved for human use) to prevent the DAS-associated adverse reactions.To test the pharmacokinetics and toxicology of whole organs and tissues after intradiscal injection of simvastatin in rabbits. To provide the information needed to support human clinical trials. Twelve male and twelve female rabbits were randomly divided into four groups control group (0 mg/ml), low dose group (0.1 mg/ml), medium dose group (1 mg/ml) and high dose group (10 mg/ml). Simvastatin at different concentrations of 10 μl was injected into L3/4, L4/5 and L5/6 intervertebral discs in each group. Poly (ethylene glycol) -poly (lactic-co-glycolic acid) -poly (ethylene glycol) (PEG-PLGA-PEG) polymer as the drug carrier. The pharmacokinetics of blood samples were measured by LC-MS/MS. Cerebrospinal fluid was obtained and the drug concentration was measured. Blood routine, blood biochemistry and urine of all animals were analyzed and evaluated. The heart, kidney, liver and spleen of each animal were observed and weighed. The intervertebral disc tissues were stained with hematoxylin and hematoxylin (H&E), and then qualitatively analyzed by optical microscopy. 28 days after intradiscal injection of simvastatin, 28 days after simvastatin intradiscal injection, there was no significant difference between the weight, food residue, blood routine, blood biochemistry, urine routine results and the weight of each organ in the four groups (p > 0.05). The serum concentration of simvastatin is lower than the lowest measurable concentration. The histological score of the intervertebral disc in the high-dose group was significantly higher than that in the other three groups at 28 days (p less then 0.05). Three doses of simvastatin were injected into male and female animals respectively, showing no toxic effects. Microscopic histological evaluation of the intervertebral disc showed that the high dose group (10 mg/ml) had damage to the intervertebral disc tissue.C. morifolium flower and C. indicum flower are two closely related herbal species with similar morphological and microscopic characteristics but are discriminated in edible and medicinal purpose. However, there is no effective approach to distinguish the two herbs. A novel workflow for quickly differentiating C. morifolium flower and C. indicum flower was developed. Firstly, the difference in anti-inflammatory effects for C. morifolium flower and C. indicum flower was characterized using lipopolysaccharide-treated rats. Then HPLC fingerprint analysis for 53 batches of C. morifolium flowers and 33 batches of C. indicum flower was carried out to deep profile the chemical components. The preliminary markers were screened out by OPLS-DA, identified by HPLC-ESI-QTOF-MS, and quantified by the improved SSDMC (single reference standard to determine multiple compounds) approach. link3 Finally, multiple statistical data mining was performed to confirm the markers and a binary logistic regression equation was built to differentiate C. morifolium flower and C. indicum flower successfully. In general, the established workflow was rapid, effective and highly feasible, which would provide a powerful tool for herb identification.Background Reverse remodeling is a clinically relevant endpoint in heart failure with reduced ejection fraction (HFrEF). Rho-kinase (ROCK) signaling cascade activation correlates with cardiac remodeling and left ventricular (LV) systolic dysfunction in HFrEF patients. Cardiac resynchronization therapy (CRT) is effective in HFrEF, especially when there is a left bundle block, as this treatment may stimulate reverse remodeling, thereby improving quality of life and prolonging survival for patients with this severe condition. Here, we evaluate the hypothesis that ROCK activation is reduced after effective CRT in HFrEF. Methods ROCK activation in circulating leukocytes was evaluated in 28 HFrHF patients, using Western blot (myosin light chain phosphatase subunit 1 phosphorylation, MYPT1p/t), before and three months after initiation of CRT. LV systolic function and remodeling were assessed by echocardiography. Results Three months after CRT, LV ejection fraction increased an average of 14.5% (p less then 0.001) in 13 patients (responders), while no change was observed in 15 patients (non-responders). End-systolic diameter decreased 16% (p less then 0.001) in responders, with no change in non-responders. ROCK activation in PBMCs decreased 66% in responders (p less then 0.05) but increased 10% in non-responders (NS). LV end-diastolic diameter was also 5.2 mm larger in non-responders vs. responders (p = 0.058). LV ejection fraction, systolic diameter, and ROCK activation levels were similar in both groups at baseline. Conclusion In HFrEF patients, 3 months of effective CRT induced reverse myocardial remodeling, and ROCK activation was significantly decreased in circulating leukocytes. Thus, decreased ROCK activation in circulating leukocytes may reflect reverse cardiac remodeling in patients with heart failure.Introduction Antibiotic resistance is a serious threat to global public health. It reduces the effectiveness of treatments for serious bacterial infections and thus increases the risk of fatal outcomes. Antibiotic prescriptions are often not in line with clinical evidence-based guidelines. The process of emergence of resistant bacteria can be slowed down by adherence to guidelines. Yet this adherence seems to be lacking in primary health care. Methods and Analysis This pragmatic quasi-experimental study using a controlled before-after design was carried out in South-East-Lower Saxony in 2018-2020. The voluntary attendance of interactive trainings with condensed presentation of current guidelines for general practitioners (GP) on antibiotic management for urinary and respiratory tract infections is regarded as intervention. Those GP not attending the trainings constitute the control group. Data were collected via questionnaires; routine health records are provided by a statutory health insurance. The primary outcome is the proportion of (guideline-based) prescriptions in relation to the relevant ICD-10 codes as well as daily defined doses and the difference in proportion of certain prescriptions according to guidelines before and after the intervention as compared to the control group.