Combined Use of Astragalus Polysaccharide and Berberine Attenuates Insulin Resistance in IR-HepG2 Cells via Regulation of the Gluconeogenesis Signaling Pathway
Insulin resistance (IR) is likely to induce metabolic syndrome and type 2 diabetes mellitus (T2DM). Gluconeogenesis (GNG) is a complex metabolic process that may result in glucose generation from certain non-carbohydrate substrates. Chinese herbal medicine astragalus polysaccharides and berberine have been documented to ameliorate IR, and combined use of astragalus polysaccharide (AP) and berberine (BBR) are reported to synergistically produce an even better effect. However, what change may occur in the GNG signaling pathway of IR-HepG2 cells in this synergistic effect and whether AP-BBR attenuates IR by regulating the GNG...
Source: Frontiers in Pharmacology - December 23, 2019 Category: Drugs & Pharmacology Source Type: research

Extract and Active Principal of the Neotropical Vine Souroubea sympetala Gilg. Block Fear Memory Reconsolidation
Background:Souroubea sympetala Gilg. is a neotropical vine native to Central America, investigated as part of a targeted study of the plant family Marcgraviaceae. Our previous research showed that extract of S. sympetala leaf and small branch extract had anxiolytic effects in animals and acts as an agonist for the GABAA receptor at the benzodiazepine binding site. To date, the potential effects of S. sympetala and its constituents on reconsolidation have not been assessed. Reconsolidation, the process by which formed memories are rendered labile and susceptible to change, may offer a window of opportunity for pharmacologic...
Source: Frontiers in Pharmacology - December 20, 2019 Category: Drugs & Pharmacology Source Type: research

Paracrine Fibroblast Growth Factor 1 Functions as Potent Therapeutic Agent for Intrahepatic Cholestasis by Downregulating Synthesis of Bile Acid
Endocrine fibroblast growth factor (FGF) 19 has been shown to be capable of maintaining bile acid (BA) homeostasis and thus hold promise to be a potential therapeutic agent for cholestasis liver disease. However, whether paracrine FGFs possess this BA regulatory activity remains to be determined. In our study, we identified that paracrine fibroblast growth factor 1 (FGF1) was selectively downregulated in the liver of alpha naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis mice, suggesting a pathological relevance of this paracrine FGF with abnormal BA metabolism. Therefore, we evaluated the effects of engineer...
Source: Frontiers in Pharmacology - December 20, 2019 Category: Drugs & Pharmacology Source Type: research

Taeumjowi-tang, a Traditional Korean Sasang Remedy, Improves Obesity-Atopic Dermatitis Comorbidity by Regulating Hypoxia-Inducible Factor 1 Alpha
Atopic dermatitis (AD) is an inflammatory disease of the skin, resulting from an immune dysfunction, that often occurs as a comorbidity of obesity. This investigation evaluated the capacity of Taeumjowi-tang (TJT), a Korean herbal formulation from the Sasang medical tradition to influence prognostic features of AD and obesity in a mouse model. Here, obesity and AD were induced by a high-fat diet (HFD) and 1-fluoro-2,4-dinitrobenzene (DNFB). Following an 8-week HFD regimen and 4 weeks of DNFB administration, the comorbid (CO) group manifested increased body weight and AD-like lesions, as compared to normal control (NC) mice...
Source: Frontiers in Pharmacology - December 20, 2019 Category: Drugs & Pharmacology Source Type: research

Suspected Hepatotoxicity With a Supercritical Carbon Dioxide Extract of Artemisia annua in Grapeseed Oil Used in New Zealand
A case series of hepatotoxicity associated with an extract of Artemisia annua L. was identified through the New Zealand spontaneous adverse drug reaction reporting system. A. annua extract, produced using a supercritical carbon dioxide extraction method and formulated with grapeseed oil, has been marketed in New Zealand as a natural product for joint health. As of 31 January 2019, the New Zealand Pharmacovigilance Centre had received 29 reports of hepatic adverse reactions occurring in patients taking A. annua extract in grapeseed oil. The case reports were assessed for patient and adverse reaction characteristics, pattern...
Source: Frontiers in Pharmacology - December 20, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacological Inhibition of Serine Proteases to Reduce Cardiac Inflammation and Fibrosis in Atrial Fibrillation
Systemic inflammation correlates with an increased risk of atrial fibrillation (AF) and thrombogenesis. Systemic inflammation alters vessel permeability, allowing inflammatory and immune cell migration toward target organs, including the heart. Among inflammatory cells infiltrating the atria, macrophages and mast cell have recently attracted the interest of basic researchers due to the pathogenic mechanisms triggered by their activation. This chemotactic invasion is likely implicated in short- and long-term changes in cardiac cell-to-cell communication and in triggering fibrous tissue accumulation in the atrial myocardium ...
Source: Frontiers in Pharmacology - December 20, 2019 Category: Drugs & Pharmacology Source Type: research

Treatment of Cystitis by Hungarian General Practitioners: A Prospective Observational Study
Conclusions: Many aspects of suboptimal cystitis management were identified (e.g. unnecessarily broad spectra agents, too long antibiotic courses). In this study, patient characteristics has weakly influenced fluoroquinolone prescribing. Based on these results there is considerable room for improvement in primary care antibiotic therapy of cystitis in Hungary. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Flunarizine Induced Parkinsonism in Migraine Group: A Nationwide Population-Based Study
Conclusion: At the population level, this study showed a complete picture of FIP in migraine patients. FIP is associated with older age, history of comorbidities, exposure to high-dose of Fz, and longer duration of exposure to Fz. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Low-Dose Dexmedetomidine Accelerates Gastrointestinal Function Recovery in Patients Undergoing Lumbar Spinal Fusion
Conclusions: Thus, low-dose dexmedetomidine accelerates gastrointestinal function recovery after lumbar spinal fusion. The effect may be partially produced by opioid-sparing effects rather than inhibition of inflammation.Clinical Trial Registration:www.chictr.org.cn, identifier ChiCTR1800018127. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Limited Associations Between 5-HT Receptor Gene Polymorphisms and Treatment Response in Antidepressant Treatment-Free Patients With Depression
Major depressive disorder has become a prominent cause of disability, as lifetime prevalence has increased to ~15% in the Western world. Pharmacological effects of serotonin (5-hydroxytryptamine, 5-HT) are mediated through 5-hydroxytryptamine receptor (5-HTR) binding. Serotonin regulation of amygdala activity is attained through activation of three 5-HT2 family receptor subtypes, 5-HT2A, 5-HT2B, and 5-HT2C. Specifically, HT2A and the HT2C receptors have similar gross cerebral distribution and function, with higher constitutive activity found in HT2C than in HT2A. We investigated the possible association of 5-HTR gene polym...
Source: Frontiers in Pharmacology - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin Signaling
Vascular calcification is a major complication of cardiovascular disease and chronic renal failure. Autophagy help to maintain a stable internal and external environment that is important for modulating arteriosclerosis, but its pathogenic mechanism is far from clear. Here, we aimed to identify the bioactive compounds from traditional Chinese medicines (TCM) that exhibit an anti-arteriosclerosis effect. In β-glycerophosphate (β-GP)-stimulated human aortic smooth muscle cells (HASMCs), the calcium level was increased and the expression of the calcification-related proteins OPG, OPN, Runx2, and BMP2 were all up-reg...
Source: Frontiers in Pharmacology - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Suhuang Antitussive Capsules-Ameliorative Effects on LPS-Induced Sputum Obstruction in Mice Through Promoting HGF Secretion
This study aims to investigate the effects and underlying mechanisms of SH Capsule on LPS-induced sputum obstruction in mice. The results showed that SH Capsule effectively promoted the tracheal phenol red output and mucociliary clearance. SH Capsule also alleviated airway inflammation-mediated mucin 5AC (MUC5AC) level through EGFR-ERK signaling. A further in vivo analysis showed that HGF inhibitor SU11274 abrogated the effects of SH Capsule on MUC5AC, well demonstrating that HGF was required for the beneficial effects of SH Capsule on expectoration in vivo. Moreover, SH Capsule promoted HGF secretion in a colon-dependent ...
Source: Frontiers in Pharmacology - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Superior Treg-Expanding Properties of a Novel Dual-Acting Cytokine Fusion Protein
Autoimmune diseases are caused by uncontrolled endogenous immune responses against healthy cells. They may develop due to an impaired function of regulatory T cells (Tregs), which normally suppress self-specific effector immune cells. Interleukin 2 (IL-2) and tumor necrosis factor (TNF) have been identified as key players that promote expansion, function, and stability of Tregs. In vivo, both low-dose IL-2 therapy and TNF receptor 2 (TNFR2) agonism were shown to expand Tregs and alleviate autoimmunity. We here designed a novel dimeric dual-acting fusion cytokine, where mouse IL-2 is genetically linked to a TNFR2-selective ...
Source: Frontiers in Pharmacology - December 18, 2019 Category: Drugs & Pharmacology Source Type: research

Long Non-Coding RNA in Drug Resistance of Non-Small Cell Lung Cancer: A Mini Review
Lung cancer is one of main causes of cancer mortality and 83% of lung cancer cases are classified as non-small cell lung cancer (NSCLC). Patients with NSCLC usually have a poor prognosis and one of the leading causes is drug resistance. With the progress of drug therapy, the emergence and development of drug resistance affected the prognosis of patients severely. Accumulating evidence reveals that long non-coding RNAs (lncRNAs), as “dark matters” of the human genome, is of great significance to drug resistance in NSCLC. Herein, we review the role of lncRNAs in drug resistance in NSCLC. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 18, 2019 Category: Drugs & Pharmacology Source Type: research

From Synthesis to Characterization of Site-Selective PEGylated Proteins
Covalent attachment of therapeutic proteins to polyethylene glycol (PEG) is widely used for the improvement of its pharmacokinetic and pharmacological properties, as well as the reduction in reactogenicity and related side effects. This technique named PEGylation has been successfully employed in several approved drugs to treat various diseases, even cancer. Some methods have been developed to obtain PEGylated proteins, both in multiple protein sites or in a selected amino acid residue. This review focuses mainly on traditional and novel examples of chemical and enzymatic methods for site-selective PEGylation, emphasizing ...
Source: Frontiers in Pharmacology - December 18, 2019 Category: Drugs & Pharmacology Source Type: research

Docetaxel and Doxorubicin Codelivery by Nanocarriers for Synergistic Treatment of Prostate Cancer
This study suggests that the DDC NPs possess noteworthy potential as prospects for the development of PCA clinical chemotherapy. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 18, 2019 Category: Drugs & Pharmacology Source Type: research

E-Synthesis: A Bayesian Framework for Causal Assessment in Pharmacosurveillance
Conclusions: E-Synthesis is highly flexible concerning the allowed input, while at the same time relying on a consistent computational system, that is philosophically and statistically grounded. Furthermore, by introducing evidential modulators, and thereby breaking up the different dimensions of evidence (strength, relevance, reliability), E-Synthesis allows them to be explicitly tracked in updating causal hypotheses. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 18, 2019 Category: Drugs & Pharmacology Source Type: research

Effectiveness of Subcutaneous Tumor Necrosis Factor Inhibitors in Patients With Ankylosing Spondylitis: A Real-World Prospective Observational Cohort Study in China
Objective: This prospective observational study investigated the efficacy of tumor necrosis factor inhibitors (TNFis) on disease activity, physical functionality, and mobility in patients with ankylosing spondylitis (AS) in a real-world setting.Methods: The Chinese Ankylosing Spondylitis Prospective Imaging Cohort (CASPIC) is an ongoing cohort study. Patients with AS were included to one of two groups: the TNFi user group included those who received TNFi at any time point; the non-TNFi user group included those who did not receive TNFi. Disease activity, physical functionality, and mobility were assessed by AS Disease Acti...
Source: Frontiers in Pharmacology - December 17, 2019 Category: Drugs & Pharmacology Source Type: research

Metabolomics and 16S rRNA Gene Sequencing Analyses of Changes in the Intestinal Flora and Biomarkers Induced by Gastrodia-Uncaria Treatment in a Rat Model of Chronic Migraine
Accumulating evidence suggests that natural medicines have notable curative effects on neurological conditions, such as migraine, that are mediated by regulating the gut microbial flora. A natural medicine pair used in traditional Chinese medicine, Gastrodia elata Blume and Uncaria rhynchophylla (Miq.) Miq. ex Havil. (GU), have shown excellent effect in treating migraine, yet the role of gut microbes in the therapeutic effect of GU in chronic migraine (CMG) is unknown. Here, we performed a 16S rRNA gene sequencing and metabolomics study of the effects of GU in a nitroglycerin (NTG)-induced rat model of CMG. Our results sho...
Source: Frontiers in Pharmacology - December 17, 2019 Category: Drugs & Pharmacology Source Type: research

The Contrasting Role of Extracellular Vesicles in Vascular Inflammation and Tissue Repair
Extracellular vesicles are a heterogeneous family of vesicles, generated from different subcellular compartments and released into the extracellular space. Composed of a lipid bilayer encompassing both soluble cytosolic material and nuclear components, these organelles have been recently described as novel regulators of intercellular communication between adjacent and remote cells. Due to their diversified composition and biological content, they portray specific signatures of cellular activation and pathological processes, their potential as diagnostic and prognostic biomarkers has raised significant interest in cardiovas...
Source: Frontiers in Pharmacology - December 17, 2019 Category: Drugs & Pharmacology Source Type: research

Effectiveness of Adalimumab for the Treatment of Psoriatic Arthritis: An Italian Real-Life Retrospective Study
Background: Few studies have evaluated the effectiveness of adalimumab in the real-life setting in psoriatic arthritis (PsA).Objective: To evaluate the 2-year retention rate of adalimumab in PsA patients. Potential baseline parameters influencing persistence on treatment were also evaluated.Methods: PsA patients from 16 Italian Rheumatology Units treated with adalimumab as first- or second-line biological therapy were retrospectively evaluated. Adalimumab retention rate was evaluated at 12 and 24 months. Logistic regression was used to evaluate the association between predictor variables and adalimumab retention rate.Resul...
Source: Frontiers in Pharmacology - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

Striatal Cholinergic Interneurons: How to Elucidate Their Function in Health and Disease
Striatal cholinergic interneurons (CINs) are the main source of acetylcholine in the striatum and are believed to play an important role in basal ganglia physiology and pathophysiology. The role of CINs in striatal function is known mostly from extracellular recordings of tonically active striatal neurons in monkeys, which are believed to correspond to CINs. Because these neurons transiently respond to motivationally cues with brief pauses, flanked by bursts of increased activity, they are classically viewed as key players in reward-related learning. However, CIN modulatory function within the striatal network has been mai...
Source: Frontiers in Pharmacology - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

Prevented and Ameliorated Pathogenesis of Crohn ’s Disease in Mice via Regulation of Inflammatory Response and Fibrosis
Crohn’s disease (CD) is a chronic, relapsing form of inflammatory bowel disease, seriously threatening human health. Thalidomide has been used for the treatment of CD. However, the effects and the possible mechanisms of thalidomide on CD are still unclear. Herein, our study demonstrated that thalidomide protected colon mucosa against trinitro-benzene-sulfonic acid (TNBS)-induced injury, diminished inflammatory infiltration and levels of IFN-γ, IGF-1, IL-6, IL-17, TNF-α, while increased the levels of IL-10 and TGF-γ. Moreover, it reversed the intestinal fibrosis and inhibited the accumulated infiltra...
Source: Frontiers in Pharmacology - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

A Significant Association Between Rhein and Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis
This study was registered with PROSPERO, number CRD42018105220.Results: Twenty-five studies involving 537 animals were included. There was significant association of rhein with levels of blood glucose (P
Source: Frontiers in Pharmacology - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

Epigenetic Regulation of Excitatory Amino Acid Transporter 2 in Neurological Disorders
Excitatory amino acid transporter 2 (EAAT2) is the predominant astrocyte glutamate transporter involved in the reuptake of the majority of the synaptic glutamate in the mammalian central nervous system (CNS). Gene expression can be altered without changing DNA sequences through epigenetic mechanisms. Mechanisms of epigenetic regulation, include DNA methylation, post-translational modifications of histones, chromatin remodeling, and small non-coding RNAs. This review is focused on neurological disorders, such as glioblastoma multiforme (GBM), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson&rsq...
Source: Frontiers in Pharmacology - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

Modulation of Transient Receptor Potential C Channel Activity by Cholesterol
Changes of cholesterol level in the plasma membrane of cells have been shown to modulate ion channel function. The proposed mechanisms underlying these modulations include association of cholesterol to a single binding site at a single channel conformation, association to a highly flexible cholesterol binding site adopting multiple poses, and perturbation of lipid rafts. These perturbations have been shown to induce reversible targeting of mammalian transient receptor potential C (TRPC) channels to the cholesterol-rich membrane environment of lipid rafts. Thus, the observed inhibition of TRPC channels by methyl-β-cycl...
Source: Frontiers in Pharmacology - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

Polygonum multiflorum-Induced Liver Injury: Clinical Characteristics, Risk Factors, Material Basis, Action Mechanism and Current Challenges
This study was aimed at reviewing the status of research on liver injury due to PM, including clinical characteristics, risk factors, material basis research and mechanism of action, with a view to understanding PM-induced hepatotoxicity, and taking reasonable and effective measures to prevent it. In short, quality control is still one of the major safety problems in TCM drug safety concerns. The model of safety monitoring and risk management of PM drugs is not yet developed. Indeed, the characteristics and risk factors associated with PM require both proper understanding and control of the risk by strengthening standardiz...
Source: Frontiers in Pharmacology - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat
Conclusion: All these results indicate that baicalin and baicalein should be used more accurately in specific diseases, especially baicalin or high content of baicalin in Scutellaria baicalensis (Tiaoqin) should be preferred in treatment of UC. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

Neuroprotective Effects of Salidroside on Cerebral Ischemia/Reperfusion-Induced Behavioral Impairment Involves the Dopaminergic System
This study examined the anti-stroke effects of salidroside in middle cerebral artery occlusion (MCAO)-induced rat model of stroke and its potential mechanisms involving the dopaminergic system. Salidroside administration increased the levels of dopamine (DA), homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in the ipsilateral striatum after induction of transient ischemia, which were assessed using microdialysis with high-performance liquid chromatography coupled with electrochemical detection (HPLC-ECD). Furthermore, treatment with salidroside ameliorated neurobehavioral impairment, assessed with the mo...
Source: Frontiers in Pharmacology - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

Angiotensin II Type I Receptor Antagonism Attenuates Nicotine-Induced Cardiac Remodeling, Dysfunction, and Aggravation of Myocardial Ischemia-Reperfusion Injury in Rats
This study sought to elucidate the role of angiotensin II type I (AT1) receptors in cardiac injury resulting from prolonged nicotine administration in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg ip) for 28 days to induce cardiac dysfunction, alone or in combination with the AT1 receptor antagonist, irbesartan (10 mg/kg, po). Vehicle-treated rats were used as controls. Rat hearts isolated from each experimental group at study endpoint were examined for changes in function, histology, gene expression, and susceptibility against acute I/R injury determined ex vivo. Rats administered nicotine alone exh...
Source: Frontiers in Pharmacology - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Efficacy and Tolerability of Lopinavir/Ritonavir- and Efavirenz-Based Initial Antiretroviral Therapy in HIV-1-Infected Patients in a Tertiary Care Hospital in Beijing, China
This study aims to assess the efficacy and adverse effect events of LPV/r plus lamivudine and tenofovir or zidovudine as an initial antiretroviral treatment in HIV-1-infected individuals for whom cannot take efavirenz (EFV) or is allergic to EFV.Methods: We performed a retrospective study of patients registering with the China’s National Free Antiretroviral Treatment Program from July 2012 to January 2017, followed at a tertiary care hospital in Beijing, China. The primary outcome was the proportion of subjects with HIV-1 RNA ≤40 copies/ml at 6 and 24 months of treatment. We assessed the immunological response and...
Source: Frontiers in Pharmacology - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe
4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe), commonly called “N-Bomb,” is a synthetic phenethylamine with psychedelic and entactogenic effects; it was available on the Internet both as a legal alternative to lysergic acid diethylamide (LSD) and as a surrogate of 3,4-methylenedioxy-methamphetamine (MDMA), but now it has been scheduled among controlled substances. 25I-NBOMe acts as full agonist on serotonergic 5-HT2A receptors. Users are often unaware of ingesting fake LSD, and several cases of intoxication and fatalities have been reported. In humans, overdoses of “N-Bomb” can ...
Source: Frontiers in Pharmacology - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Genome Analysis Reveals a Synergistic Mechanism of Ursodeoxycholic Acid and Jasminoidin in Mice Brain Repair After Ischemia/Reperfusion: Crosstalk Among Muti-Pathways
Studies have shown that combination drug therapy which corresponding treatment involves multiple genes and targets is more effective against cerebral ischemia. To identify the synergistic mechanism of ursodeoxycholic acid and jasminoidin based on differential pathway network, which protect against brain ischemia-reperfusion injury. Totally 115 mice with focal cerebral ischemia-reperfusion injury were allocated into five groups: sham, vehicle, ursodeoxycholic acid (UA), jasminoidin (JA), and JA and UA combination group (JU). The differentially expressed genes identified by microarray which consisted of 11,644 complementary ...
Source: Frontiers in Pharmacology - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Incidences of Hypothyroidism Associated With Surgical Procedures for Thyroid Disorders: A Nationwide Population-Based Study
Conclusion: Findings suggest that thyroidectomy was associated with transient postoperative hypothyroidism in thyroid disorder patients. The bilateral-total surgical procedure was strongly associated with temporary postoperative hypothyroidism. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Drug-Induced Liver Injury: Biomarkers, Requirements, Candidates, and Validation
The hepatotoxicity of drugs is the main cause of drug withdrawal from the pharmaceutical market and interruption of the development of new molecules. Biomarkers are useful in several situations. In case of suspected drug-induced liver injury (DILI), biomarkers can be used to confirm liver damage, its severity, prognosis, confirm drug causality, or define the type of DILI. In this review, we will first present the currently used biomarkers and candidate biomarkers for the future. The current biomarkers are certainly very helpful including with the assistance of diagnostic method such the Roussel Uclaf Causality Assessment M...
Source: Frontiers in Pharmacology - December 11, 2019 Category: Drugs & Pharmacology Source Type: research

Six-Year Immunologic Recovery and Virological Suppression of HIV Patients on LPV/r-Based Second-Line Antiretroviral Treatment: A Multi-Center Real-World Cohort Study in China
The World Health Organization guidelines recommend lopinavir/ritonavir (LPV/r) as a second-line antiretroviral therapy (ART) for HIV-infected adults in middle-income and low-income countries as a protease inhibitor boost based on clinical trials; however, the real-world safety and efficacy remain unknown. Therefore, we conducted a large-scale, multicenter retrospective cohort study to evaluate the efficacy and safety of LPV/r-based ART among HIV-infected adults in China in whom first-line therapy failed. The data were obtained from a national database covering 17 clinics in China for six years of follow-up from 2009 to 201...
Source: Frontiers in Pharmacology - December 11, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacological Profile of the Sodium Current in Human Stem Cell-Derived Cardiomyocytes Compares to Heterologous Nav1.5+ β1 Model
The cardiac Nav1.5 mediated sodium current (INa) generates the upstroke of the action potential in atrial and ventricular myocytes. Drugs that modulate this current can therefore be antiarrhythmic or proarrhythmic, which requires preclinical evaluation of their potential drug-induced inhibition or modulation of Nav1.5. Since Nav1.5 assembles with, and is modulated by, the auxiliary β1-subunit, this subunit can also affect the channel’s pharmacological response. To investigate this, the effect of known Nav1.5 inhibitors was compared between COS-7 cells expressing Nav1.5 or Nav1.5+β1 using whole-cell voltage ...
Source: Frontiers in Pharmacology - December 11, 2019 Category: Drugs & Pharmacology Source Type: research

In Vitro Research Reproducibility: Keeping Up High Standards
Concern regarding the reproducibility of observations in life science research has emerged in recent years, particularly in view of unfavorable experiences with preclinical in vivo research. The use of cell-based systems has increasingly replaced in vivo research and the application of in vitro models enjoys an ever-growing popularity. To avoid repeating past mistakes, high standards of reproducibility and reliability must be established and maintained in the field of in vitro biomedical research. Detailed guidance documenting the appropriate handling of cells has been authored, but was received with quite disparate percep...
Source: Frontiers in Pharmacology - December 10, 2019 Category: Drugs & Pharmacology Source Type: research

Fibromodulin – A New Target of Osteoarthritis Management?
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 10, 2019 Category: Drugs & Pharmacology Source Type: research

Transcriptomic Validation of the Protective Effects of Aqueous Bark Extract of Terminalia arjuna (Roxb.) on Isoproterenol-Induced Cardiac Hypertrophy in Rats
This study for the first time reveals that TA partially or completely restores the gene regulatory network perturbed by ISO treatment in rat heart; signifying its efficacy in checking ISO-induced cardiac hypertrophy. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 10, 2019 Category: Drugs & Pharmacology Source Type: research

Catalpol Ameliorates Podocyte Injury by Stabilizing Cytoskeleton and Enhancing Autophagy in Diabetic Nephropathy
This study mainly investigated the protective effect and potential mechanism of catalpol on podocyte injury of DN in vivo and in vitro. The results indicated that the pathological features of DN in mice were markedly ameliorated after treatment with catalpol. Moreover, podocyte foot process effacement, and down-regulation of nephrin and synaptopodin expression in DN mice were also significantly improved after treatment with catalpol. In vitro, catalpol rescued disrupted cytoskeleton and increased migration ratio in podocytes induced by high glucose, the effect might be attributable to the inhibition of RhoA and Cdc42 activ...
Source: Frontiers in Pharmacology - December 10, 2019 Category: Drugs & Pharmacology Source Type: research

Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice
Conclusion: Our findings revealed that EL significantly reduced blood uric acid levels, prevented pathological changes of kidney in PO induced hyperuricemia animal model, and improved renal urate transports. We partly clarified the mechanism was related to suppressing effect of URAT1 by quassinoid in EL. This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 10, 2019 Category: Drugs & Pharmacology Source Type: research

The Role of Biosimilars in Uveitis: Long-Term Real-World Outcomes of the Switch From Original to Biosimilar TNF-Alpha Inhibitors
Conclusions: The switch to biosimilars represents a feasible treatment choice associated with the maintenance of clinical efficacy in patients with non-infectious uveitis previously treated with the corresponding originator anti-TNF-α biologic agents. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 9, 2019 Category: Drugs & Pharmacology Source Type: research

The Pharmacology of Visual Hallucinations in Synucleinopathies
Visual hallucinations (VH) are commonly found in the course of synucleinopathies like Parkinson's disease and dementia with Lewy bodies. The incidence of VH in these conditions is so high that the absence of VH in the course of the disease should raise questions about the diagnosis. VH may take the form of early and simple phenomena or appear with late and complex presentations that include hallucinatory production and delusions. VH are an unmet treatment need. The review analyzes the past and recent hypotheses that are related to the underlying mechanisms of VH and then discusses their pharmacological modulation. Recent m...
Source: Frontiers in Pharmacology - December 9, 2019 Category: Drugs & Pharmacology Source Type: research

The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer ’s Disease
According to the World Alzheimer’s report, dementia was estimated to affect 50 million worldwide in 2018, number expected to increase to more than 150 million within 30 years. Alzheimer’s disease is the most common type of dementia, accounting on its own for 2/3 of all dementia cases. The initial signs and symptoms of Alzheimer’s disease relate to progressive cognitive decline, inexorably progressing until the loss of independence. Neuropsychiatric and behavioral symptoms may occur during the progression of the disease; around 20% of patients without any behavioral symptoms at the diagnosis will experienc...
Source: Frontiers in Pharmacology - December 6, 2019 Category: Drugs & Pharmacology Source Type: research

Incidence of Immune Checkpoint Inhibitor-Associated Diabetes: A Meta-Analysis of Randomized Controlled Studies
Conclusions: New-onset diabetes is uncommon with ICIs but the risk is increased compared with placebo or another therapeutic strategy. However, more studies are warranted to substantiate these findings across ICIs. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 6, 2019 Category: Drugs & Pharmacology Source Type: research

Harmful Effects of Smoking Cannabis: A Cerebrovascular and Neurological Perspective
Apart from being used as a medicine, cannabis or marijuana is the most widely abused recreational drug all over the world. The legalization and decriminalization of cannabis in Canada and various states of USA may be the underlying reason of the widespread popularity of it among young population. Various studies have reported about the relationship between cannabis use and different detrimental effects like cardiovascular, cerebrovascular, and neurological complications among different age groups. Specifically, the young population is getting adversely affected by this, harmful yet, readily accessible recreational drug. Al...
Source: Frontiers in Pharmacology - December 6, 2019 Category: Drugs & Pharmacology Source Type: research

Integrated UPLC-Q/TOF-MS Technique and MALDI-MS to Study of the Efficacy of YiXinshu Capsules Against Heart Failure in a Rat Model
In this study, a metabonomic approach based on integrated UPLC-Q/TOF-MS technique and MALDI-MS was utilized to explore potential metabolic biomarkers that may help increase the understanding of heart failure (HF) and in order to assess the potential mechanisms of YXSC against HF. Plasma metabolic profiles were analyzed by UPLC-Q/TOF-MS with complementary hydrophilic interaction chromatography and reversed-phase liquid chromatography. Moreover, time-course analysis at the 2nd, 4th, and 10th week after permanent occlusion was conducted. In an effort to identify a more reliable potential metabolic marker, common metabolic mar...
Source: Frontiers in Pharmacology - December 6, 2019 Category: Drugs & Pharmacology Source Type: research

Arsenic Species in Cordyceps sinensis and Its Potential Health Risks
This study contributed to the toxicity reveal, safety evaluation, and risk assessment of arsenic in C. sinensis. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 6, 2019 Category: Drugs & Pharmacology Source Type: research

Application and Mechanisms of Triptolide in the Treatment of Inflammatory Diseases —A Review
Bioactive compounds from medicinal plants with anti-inflammatory and immunosuppressive effects have been emerging as important sources of drugs for the treatment of inflammatory disorders. Triptolide, a diterpene triepoxide, is a pharmacologically active compound isolated from Tripterygium wilfordii Hook F (TwHF) that is used as a remedy for inflammatory and autoimmune diseases. As the most promising bioactive compound obtained from TwHF, triptolide has attracted considerable interest recently, especially for its potent anti-inflammatory and immunosuppressive activities. Over the past few years, an increasing number of stu...
Source: Frontiers in Pharmacology - December 6, 2019 Category: Drugs & Pharmacology Source Type: research