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Background Acute diarrhea is still a common and serious disease. TJ-M2010-5 mw The causes of acute diarrhea are very complicated. Therefore, we need to find a medicine to control diarrhea symptoms, save time for diagnosis of pathogens, and prevent drug abuse. Ellagic acid (EA), a natural polyphenol drug, has anti-diarrhea effects. However, the action mechanisms of EA for non-specific diarrhea have not been characterized. Materials and Methods To study the mechanisms of EA, mice were divided into four groups. Group C were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml physiological saline, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group D were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group E were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then afcastor oil-induced inflammation and diarrhea by activating the PPAR signaling pathway and a method was used to study the mechanism of EA. Copyright © 2020 Chen, Yang and Sheng.Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder that slowly destroys memory. The precise mechanism of AD is still not entirely understood and remains under discussion; it is believed to be a multifactorial disease in which a number of mechanisms are involved in its pathogenesis. Worldwide, near 37 million people suffer from the effects of AD. As a cause of death for elderly, it is predicted that AD will rank third in the coming years, just behind cancer and heart disease. Unfortunately, AD remains an incurable condition. Despite the devastating problems associated with AD, there are only four FDA approved drugs for palliative treatment of this pathology. Hence, renewed scientific efforts are required not only to uncover more insights into the AD process but also to develop more efficient pharmacological tools against this disease. Due to the complexity and multiple mechanisms at play in the progression of AD, the development of drugs by rational design is extremely diffif substitution patterns that display multi-target neuroactivity against multiple events involved in AD. This benzofuran chemical framework will establish a multi-target chemical space that could set the basis for the development of super drugs against AD. Copyright © 2020 Cabrera-Pardo, Fuentealba, Gavilán, Cajas, Becerra and Napiórkowska.Introduction Uwhangchungsimwon (UCW) is one of the most representative standardized herbal drugs for the treatment of central nervous system diseases, including mood disorders, and has been used for over 600 years in Korea and China. In spite of the long clinical application of UCW, no experimental evidence for its use against depressive disorders exists. Here, we performed an animal study to investigate the anti-depressive effect of UCW and the underlying mechanisms. Methods A social isolation-induced depressive-like model was produced using C57BL/6J male mice by housing the mice individually for 31 days, and the mice underwent daily oral administration of distilled water, UCW (100, 200, 400 mg/kg) or fluoxetine (20 mg/kg) during the final 17 days. A tail suspension test (TST), forced swimming test (FST), and open field test (OFT) were used to explore the effects of UCW on depressive-like behaviors. 5-Hydroxytryptamine (5-HT) was measured in the dorsal raphe nuclei (DRN) using immunofluorescence. The serum cay involve regulating the serotonergic system, the hypothalamic-pituitary-adrenal (HPA) axis, and neurotrophin. Copyright © 2020 Oh, Lee, Kim, Oh, Kim, Lee, Cho, Jeon, Cho and Son.Introduction The role of combination treatment in the management of carbapenem-resistant Enterobacteriaceae infections (CRE) is still unclear. There have been no meta-analysis comparing the efficiency of triple therapy in treating CRE infections with that of double therapy. In this perspective, we conducted a meta-analysis to clarify whether triple therapy is superior to double therapy in treating patients with CRE infections. Methods We performed a systematic review, using PubMed and Embase without any restrictions until October 2019. Risk ratio (RR) with 95% CI were pooled to evaluate the effect of intervention. Results A total of 33 studies with 1,441 subjects were identified. Pooled analysis showed that triple therapy was not associated with a reduced mortality compared with double therapy (HR 0.99 95% CI 0.85-1.14, P = 0.85). Conclusions This meta-analysis suggests that triple therapy is not superior to double therapy in the treatment of patients with CRE infections, although the quality of evidence is generally low based on current literatures. Future well-defined, randomized controlled trials will be required to elucidate the role of triple therapy in the treatment of CRE infections. Copyright © 2020 Wang, Tong, Huang, Zhang, Wang, Wu, Liu and Fan.Long-term use of imatinib is effective and well-tolerated in children with chronic myeloid leukaemia (CML) yet defining an optimal dosing regimen for imatinib in younger patients is a challenge. The potential interactions between imatinib and coadministered drugs in this "special" population also remains largely unexplored. This study implements a physiologically based pharmacokinetic (PBPK) modeling approach to investigate optimal dosing regimens and potential drug interactions with imatinib in the paediatric population. A PBPK model for imatinib was developed in the Simcyp Simulator (version 17) utilizing in silico, in vitro drug metabolism, and in vivo pharmacokinetic data and verified using an independent set of published clinical pharmacokinetic data. The model was then extrapolated to children and adolescents (aged 2-18 years) by incorporating developmental changes in organ size and maturation of drug-metabolising enzymes and plasma protein responsible for imatinib disposition. The PBPK model described imatinib pharmacokinetics in adult and paediatric populations and predicted drug interaction with carbamazepine, a cytochrome P450 (CYP)3A4 and 2C8 inducer, with a good accuracy (evaluated by visual inspections of the simulation results and predicted pharmacokinetic parameters that were within 1.25-fold of the clinically observed values). The PBPK simulation suggests that the optimal dosing regimen range for imatinib is 230-340 mg/m2/d in paediatrics, which is supported by the recommended initial dose for treatment of childhood CML. The simulations also highlighted that children and adults being treated with imatinib have similar vulnerability to CYP modulations. A PBPK model for imatinib was successfully developed with an excellent performance in predicting imatinib pharmacokinetics across age groups. This PBPK model is beneficial to guide optimal dosing regimens for imatinib and predict drug interactions with CYP modulators in the paediatric population. Copyright © 2020 Adiwidjaja, Boddy and McLachlan.
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