Fremanezumab autoinjector pencil to prevent migraine headache

We used steric-clashes alleviating receptors (SCAR), a computer-aided drug discovery strategy developed by us recently for in silico screening. By combining computational screening and experimental validation, we successfully identified two approved drugs that have inhibitory potency on AdoMetDC's enzymatic activity. SCAR was previously shown to be suitable for the discovery of both covalent and non-covalent inhibitors, and this work further demonstrated the value of the SCAR strategy in drug repurposing. Copyright © 2020 Zhang, Zheng, Zhou and Liu.Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by chronic synovitis, bone erosion, and bone loss. Erzhi Pill (EZP), a classic Chinese patent medicine, is often used to treat osteoporosis and shows a capacity for bone metabolism regulation. Methotrexate (MTX), an essential drug for RA treatment, has been reported to inhibit generalized bone loss in RA patients. However, the combined therapeutic effects and mechanism of EZP and MTX in RA have not been fully elucidated. The aim of this study was to investigate the synergistic effect of EZP and MTX on RA and to explore the underlying mechanism through network pharmacological prediction and experimental verification. Chemical compounds of EZP, human target proteins of EZP and MTX, and RA-related human genes were identified in the Encyclopedia of Traditional Chinese Medicine database, PubChem database, and NCBI database, respectively. The molecular network of EZP and MTX in RA was generated and analyzed with Ingenuity Pathway AnalyIn vitro experiments showed that EZP combined with MTX could also improve the expression of genes related to the Wnt1/LRP5/β-catenin pathway. This study demonstrated that EZP in combination with MTX played a synergistic role in regulating OBs in RA, which was connected to the modulatory effect of EZP and MTX on the Wnt1/LRP5/β-catenin signaling pathway. Copyright © 2020 Li, Lu, Fan, Li, Lu, Tan, Xia, Zhao, Fan and Xiao.We have identified distinct histamine pharmacodynamic response phenotypes in children with allergic disease utilizing histamine iontophoresis with laser Doppler (HILD). These response phenotypes may be relevant in guiding therapeutic decision making for agents targeting the allergic response pathways. However, the reliability of these response phenotypes has not been assessed. Therefore, we performed HILD in children with allergic rhinitis and/or asthma on two to three separate occasions. HILD response-time data were analyzed in NONMEM using a linked effect PKPD model. Examination of observed vs. classified response phenotypes predicted response plots and the sum of residuals. The intraclass correlation coefficient (ICC) was used to determine the reliability of phenotype classification. Eighty-two percent of children exhibited a reliable histamine response phenotype [intraclass correlation coefficient 0.77 (95% CI 0.44-0.93]. These preliminary results suggest moderate reliability of HILD response phenotype in children. Further exploration is needed to determine contributions to phenotype variability. Copyright © 2020 Kumar, Liu, Sherwin and Jones.Chronic pain is a common detrimental condition that affects around 20% of the world population. The current drugs to treat chronic pain states, especially neuropathic pain, have a limited clinical efficiency and present significant adverse effects that complicates their regular use. selleck chemical Recent studies have proposed new therapeutic strategies focused on the pharmacological modulation of G-protein-coupled receptors, transporters, enzymes, and ion channels expressed on the nociceptive pathways. The present work intends to summarize recent advances on the pharmacological modulation of pentameric ligand-gated ion channels, which plays a key role in pain processing. Experimental data have shown that novel allosteric modulators targeting the excitatory nicotinic acetylcholine receptor, as well as the inhibitory GABAA and glycine receptors, reverse chronic pain-related behaviors in preclinical assays. Collectively, these evidences strongly suggest the pharmacological modulation of pentameric ligand-gated ion channels is a promising strategy towards the development of novel therapeutics to treat chronic pain states in humans. Copyright © 2020 Lara, Burgos, Moraga-Cid, Carrasco and Yévenes.Background In geriatric age, cognitive impairment and cardiovascular disorders are frequent comorbidities. Age-related anatomical and functional cardiac changes, including the autonomic system, could interfere with the control of different cognitive domains. Therefore, we assess the relationship between long-term heart rate variability (HRV), as a measure of autonomic nervous system (ANS) functioning, and cognitive performance in elderly patients representative of outpatients in a real-life setting. Methods Of 155 elderly outpatients (aged >65 years) screened, 117 enrolled patients underwent anthropometric evaluation, cardiac assessment by 12-lead electrocardiogram, 24-h ECG recording, and blood pressure (BP) measurement, as well as global cognitive evaluation by a standardized multidimensional assessment, including the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment test (MoCA). HRV analysis was performed on 24-h ECG recordings focusing on time-domain indices [Standard deviation of theperformances and a moderate prevalence of autonomic function appears dependent on long-term changes in heart rate, mediated by sympathetic activation. Copyright © 2020 Dalise, Prestano, Fasano, Gambardella, Barbieri and Rizzo.Dendritic spines are the morphological basis of excitatory synapses in the cortex and their size and shape correlates with functional synaptic properties. Recent experiments show that spines exhibit large shape fluctuations that are not related to activity-dependent plasticity but nonetheless might influence memory storage at their synapses. To investigate the determinants of such spontaneous fluctuations, we propose a mathematical model for the dynamics of the spine shape and analyze it in 2D-related to experimental microscopic imagery-and in 3D. We show that the spine shape is governed by a local imbalance between membrane tension and the expansive force from actin bundles that originates from discrete actin polymerization foci. Experiments have shown that only few such polymerization foci co-exist at any time in a spine, each having limited life time. The model shows that the momentarily existing set of such foci pushes the membrane along certain directions until foci are replaced and other directions may now be affected.