Downregulation of miR-3568 Protects Against Ischemia/Reperfusion-Induced Cardiac Dysfunction in Rats and Apoptosis in H9C2 Cardiomyocytes Through Targeting TRIM62
In conclusion, our study suggests that miR-3568 promotes simulated I/R-induced apoptosis in H9C2 cardiomyocytes through targeting TRIM62. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 13, 2020 Category: Drugs & Pharmacology Source Type: research

A Relative Bioavailability Study of Two Misoprostol Formulations Following a Single Oral or Sublingual Administration
ConclusionThe relative bioavailability between Angusta and Cytotec could not be confirmed as being equal at the 25 µg or 50 µg level because the 90% CI-values when comparing the ratios for AUC, AUC(0−t), and Cmax were wider than accepted. The reason for this could be the real-life, non-standardized circumstances in which the study was conducted. Sublingual administration seems to have higher bioavailability than oral administration. More studies are needed to ascertain an optimal dosage regime balancing both safety and efficacy for mother and child.Clinical Trial Registrationwww.ClinicalTrials.gov, identi...
Source: Frontiers in Pharmacology - February 12, 2020 Category: Drugs & Pharmacology Source Type: research

In Vitro Antibacterial Experiment of Fuzheng Jiedu Huayu Decoction Against Multidrug-Resistant Pseudomonas aeruginosa
ConclusionDrawing the growth curve of the experimental strain had high application value for ensuring the accuracy of the drug sensitivity test results. TCM combined with antibiotics could enhance the antibacterial and direct destruction effect of bacteria in vitro, thereby inhibiting bacterial resistance to a certain extent. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 12, 2020 Category: Drugs & Pharmacology Source Type: research

Improved Computational Identification of Drug Response Using Optical Measurements of Human Stem Cell Derived Cardiomyocytes in Microphysiological Systems
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) hold great potential for drug screening applications. However, their usefulness is limited by the relative immaturity of the cells’ electrophysiological properties as compared to native cardiomyocytes in the adult human heart. In this work, we extend and improve on methodology to address this limitation, building on previously introduced computational procedures which predict drug effects for adult cells based on changes in optical measurements of action potentials and Ca2+ transients made in stem cell derived cardiac microtissues. This meth...
Source: Frontiers in Pharmacology - February 12, 2020 Category: Drugs & Pharmacology Source Type: research

Intravitreal Delivery of Melatonin Is Protective Against the Photoreceptor Loss in Mice: A Potential Therapeutic Strategy for Degenerative Retinopathy
Melatonin is a circadian hormone with potent cytoprotective effects. Retinitis pigmentosa (RP) comprises a heterogeneous group of inherent retinopathies that characterized by the photoreceptor death in bilateral eyes. The N-methyl-N-nitrosourea (MNU) administered mouse is a type of chemically induced RP model with rapid progressive rate. We intend to study the melatonin mediated effects on the MNU administered mice. Melatonin was delivered into the vitreous body of the MNU administered mice. Subsequently, the melatonin treated mice were subjected to histological analysis, optokinetic behavior tests, spectral-domain optical...
Source: Frontiers in Pharmacology - February 12, 2020 Category: Drugs & Pharmacology Source Type: research

Protective Effects of Amlodipine Pretreatment on Contrast-Induced Acute Kidney Injury And Overall Survival In Hypertensive Patients
ConclusionIn conclusion, we first found amlodipine treatment before contrast exposure played a role in protecting hypertensive patients from CI-AKI and prolonging survival. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 11, 2020 Category: Drugs & Pharmacology Source Type: research

Fibroblast Growth Factor 22 Inhibits ER Stress-Induced Apoptosis and Improves Recovery of Spinal Cord Injury
This study also suggested a new tendency of FGF22 therapy development in central neural system injuries, which involved chronic ER stress-induced apoptosis. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 11, 2020 Category: Drugs & Pharmacology Source Type: research

Baicalin Protects Against 17 α-Ethinylestradiol-Induced Cholestasis via the Sirtuin 1/Hepatic Nuclear Receptor-1α/Farnesoid X Receptor Pathway
In this study, we demonstrated that baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum biomarkers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic BAs. In addition, baicalin protected against estrogen-induced liver injury by up-regulation of the expression of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat, Sult2a1) in EIC rats. We showed that baicalin significantly inhibited ...
Source: Frontiers in Pharmacology - February 11, 2020 Category: Drugs & Pharmacology Source Type: research

Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling
Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps take up Ca2+ from the cytoplasm to maintain the balance of intracellular Ca2+. A decline in expression or activity of SERCA results in persistent store-operated calcium entry (SOCE). In cardiomyocytes as well as vascular smooth muscle cells (SMCs), SERCA2 acts as an important regulator of calcium cycling. The purpose of this study is to identify and better understand the role of transglutaminases2 (TG2) as a key factor involved in SERCA2 serotonination (s-SERCA2) and to elucidate the underlying mechanism of action. Human pulmonary venous smooth muscle cell in normal pul...
Source: Frontiers in Pharmacology - February 11, 2020 Category: Drugs & Pharmacology Source Type: research

Clemastine Fumarate Protects Against Myocardial Ischemia Reperfusion Injury by Activating the TLR4/PI3K/Akt Signaling Pathway
The objective of this study is to determine the mechanism by which CLE relieves MIRI in cardiomyocytes and its relationship with the TLR4/PI3K/Akt signaling pathway. CCK8 analysis was used to test the optimal concentration of TLR4 inhibitor CLI-095 and TLR4 agonist lipopolysaccharide (LPS) on MIRI. The expression of inflammatory factors, oxidative stress response, cell damage, and intracellular calcium redistribution of cardiomyocytes were examined using the ELISA kits, Total Superoxide Dismutase Assay Kit with WST-8 and Lipid Peroxidation MDA Assay Kit, LDH Cytotoxicity Assay Kit, and laser scanning confocal microscope. T...
Source: Frontiers in Pharmacology - February 10, 2020 Category: Drugs & Pharmacology Source Type: research

Circulating Tumor DNA-Based Detection of Microsatellite Instability and Response to Immunotherapy in Pancreatic Cancer
We present a case of pancreatic cancer whose microsatellite instability status was identified on liquid biopsy (circulating tumor DNA testing). Our patient showed a dramatic ongoing durable response to immunotherapy. We were able to do serial monitoring with liquid biopsy that showed clinical utility and validity. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 10, 2020 Category: Drugs & Pharmacology Source Type: research

Anemonin Attenuates RANKL-Induced Osteoclastogenesis and Ameliorates LPS-Induced Inflammatory Bone Loss in Mice via Modulation of NFATc1
This study aimed to investigate the potential effect of ANE on osteoclastogenesis and inflammatory bone loss in mice. In in vitro studies, ANE suppressed RANKL-stimulated osteoclast differentiation and function by downregulating the expression of osteoclast master transcriptor NFATc1, as well as its upstream transcriptor c-Fos, by decreasing NF-κB and ERK1/2 signaling. Interestingly, ANE did not change the phosphorylation and degradation of IκB-α and activation of JNK and p38 MAPKs. However, ANE repressed the phosphorylation of MSK-1 which is the downstream target of ERK1/2 and p38 MAPK and can phosphoryl...
Source: Frontiers in Pharmacology - February 10, 2020 Category: Drugs & Pharmacology Source Type: research

Anticancer Effects of Wild Mountain Mentha longifolia Extract in Adrenocortical Tumor Cell Models
Mint [Mentha longifolia (L.) Hudson] is an aromatic plant that belongs to Lamiaceae family. It is traditionally used as herbal tea in Europe, Australia and North Africa and shows numerous pharmacological effects, such as spasmolytic, antioxidant, antimicrobial and anti-hemolytic. Recently, its antiproliferative role has been suggested in a small number of tumor cell models, but no data are available on adrenocortical carcinoma, a malignancy with a survival rate at 5 years of 20%–30% which frequently metastasize. This work aimed to study the effects of Mentha longifolia L. crude extract (ME) on two adrenocortical tumo...
Source: Frontiers in Pharmacology - February 10, 2020 Category: Drugs & Pharmacology Source Type: research

Mangiferin Ameliorates Hyperuricemic Nephropathy Which Is Associated With Downregulation of AQP2 and Increased Urinary Uric Acid Excretion
This study aimed to evaluate the effect of mangiferin treatment in HN. In a mouse model of HN, we observed lower circulating urate levels and ameliorated renal dysfunction with mangiferin treatment, which was associated with reduced renal inflammation and fibrosis. We next investigated the mechanism of urate lowering effect of mangiferin. Metabolic cage experiment showed that mangiferin-administrated mice excreted significantly more urinary uric acid due to elevated urine output, but no marked change in urine uric acid concentration. Expressions of water channels and urate transporters were further assessed by western blot...
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

Lignans: Quantitative Analysis of the Research Literature
The current study provides a comprehensive overview and analysis of the lignan literature. Data for the current study were extracted from the electronic Web of Science Core Collection database via the search string TOPIC = (“lignan*”) and processed by the VOSviewer software. The search yielded 10,742 publications. The ratio of original articles to reviews was 14.6:1. Over 80% of the analyzed papers have been published since the year 2000 and nearly 50% since the year 2010. Many of the publications were focused on pharmacology, chemistry, and plant sciences. The United States and Asian countries, such as China, ...
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

Depressive Symptoms in the Elderly —An Early Symptom of Dementia? A Systematic Review
ConclusionsThe exact nature of the relationship between depressive symptoms and dementia in the elderly remains inconclusive, with multiple studies supporting both the risk factor and prodromal hypotheses. Some provide arguments for common risk factors. It seems unlikely that there is no connection at all. We conclude that at least in a significant part of the patients, depressive symptoms and dementia are related. This may be due to common risk factors and/or depressive symptoms being a prodromal symptom of dementia and/or depression being a risk factor for dementia. These causal associations possibly overlap in some pati...
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

Hydrogen Sulfide Attenuates Particulate Matter-Induced Emphysema and Airway Inflammation Through Nrf2-Dependent Manner
ConclusionHydrogen sulfide played a protect role in PM-induced mice emphysema and airway inflammation by inhibiting NLRP3 inflammasome formation and apoptosis via Nrf2-dependent pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

The Application of DVDMS as a Sensitizing Agent for Sono-/Photo-Therapy
Both photodynamic therapy (PDT) and sonodynamic therapy (SDT) are fast growing activated therapies by using light or ultrasound to initiate catalytic reaction of sensitizing agents, showing great potentials in clinics because of high safety and noninvasiveness. Sensitizers are critical components in PDT and SDT. Sinoporphyrin sodium (DVDMS) is an effective constituent derived from Photofrin that has been approved by FDA. This review is based on previous articles that explore the applications of DVDMS mediated photodynamic/sonodynamic cancer therapy and antimicrobial chemotherapy. Researchers utilize different cell lines, d...
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

Alterations of Astrocytes in the Context of Schizophrenic Dementia
The levels of the astrocyte markers (GFAP, S100B) were increased unevenly in patients with schizophrenia. Reactive astrogliosis was found in approximately 70% of patients with schizophrenia. The astrocytes play a major role in etiology and pathogenesis of schizophrenia. Astrocytes produce the components that altered in schizophrenia extracellular matrix system which are involved in inflammation, functioning of interneurons, glio-, and neurotransmitter system, especially glutamate system. Astrocytes activate the interneurons through glutamate release and ATP. Decreased expression of astrocyte glutamate transporters was obse...
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

Bioactivity, Compounds Isolated, Chemical Qualitative, and Quantitative Analysis of Cymbaria daurica Extracts
This study provides a chemical basis for further characterization and utilization of C. daurica, which could be a potential source of novel anti-diabetic and anti-inflammatory agents. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

Distinct Types of Cell Death and the Implication in Diabetic Cardiomyopathy
Diabetic cardiomyopathy (DCM) is a chronic complication of diabetes mellitus, characterized by abnormalities of myocardial structure and function. Researches on the models of type 1 and type 2 diabetes mellitus as well as the application of genetic engineering technology help in understanding the molecular mechanism of DCM. DCM has multiple hallmarks, including hyperglycemia, insulin resistance, increased free radical production, lipid peroxidation, mitochondrial dysfunction, endothelial dysfunction, and cell death. Essentially, cell death is considered to be the terminal pathway of cardiomyocytes during DCM. Morphological...
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

Fibroblast Growth Factor 10 Attenuates Renal Damage by Regulating Endoplasmic Reticulum Stress After Ischemia –Reperfusion Injury
Renal ischemia–reperfusion (I/R) injury is a predominant cause of acute kidney injury (AKI), the pathologic mechanism of which is highly complex involving reactive oxygen species (ROS) accumulation, inflammatory response, autophagy, apoptosis as well as endoplasmic reticulum (ER) stress. Fibroblast growth factor 10 (FGF10), as a multifunctional growth factor, plays crucial roles in embryonic development, adult homeostasis, and regenerative medicine. Herein, we investigated the molecular pathways underlying the protective effect of FGF10 on renal I/R injury using Sprague–Dawley rats. Results showed that administ...
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

Clonal Selection of a Novel Deleterious TP53 Somatic Mutation Discovered in ctDNA of a KIT/PDGFRA Wild-Type Gastrointestinal Stromal Tumor Resistant to Imatinib
The standard of care for the first-line treatment of advanced gastrointestinal stromal tumor (GIST) is represented by imatinib, which is given daily at a standard dosage until tumor progression. Resistance to imatinib commonly occurs through the clonal selection of genetic mutations in the tumor DNA, and an increase in imatinib dosage was demonstrated to be efficacious to overcome imatinib resistance. Wild-type GISTs, which do not display KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations, are usually primarily insensitive to imatinib and tend to rapidly relapse in course of treatment. Here we report t...
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

Impact of Population and Pharmacogenetics Variations on Efavirenz Pharmacokinetics and Immunologic Outcomes During Anti-Tuberculosis Co-Therapy: A Parallel Prospective Cohort Study in Two Sub-Sahara African Populations
Efavirenz-based combination antiretroviral-therapy (cART) is the recommended regimen during tuberculosis (TB) therapy. In a multi-national parallel prospective-cohort study, we investigated the impact of population and pharmacogenetic variations for efavirenz pharmacokinetics, auto-induction, and immunologic outcome during antituberculosis treatment. A total of 921 treatment-naïve HIV patients with (196 Ethiopians and 231 Tanzanians) or without TB co-infection (285 Ethiopians and 209 Tanzanians) were enrolled and treated with efavirenz-based cART. TB-HIV patients started rifampicin-based anti-TB therapy 4 weeks before...
Source: Frontiers in Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Source Type: research

Celastrol Suppresses Glioma Vasculogenic Mimicry Formation and Angiogenesis by Blocking the PI3K/Akt/mTOR Signaling Pathway
Angiogenesis and vasculogenic mimicry (VM) are thought to be the predominant processes ensuring tumor blood supply during the growth and metastasis of glioblastoma (GBM). Celastrol has potential anti-glioma effects, however the mechanisms underlying these effects remain unclarified. Recent studies have shown that the PI3K/Akt/mTOR signaling pathway is closely related to angiogenesis and VM formation. In the present study, we have demonstrated, for the first time, that celastrol eliminated VM formation by blocking this signaling pathway in glioma cells. By the treatment of celastrol, tumor growth was suppressed, tight junct...
Source: Frontiers in Pharmacology - February 6, 2020 Category: Drugs & Pharmacology Source Type: research

Editorial: Innovative Biologics and Drugs to Target Renal Inflammation
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 6, 2020 Category: Drugs & Pharmacology Source Type: research

Naturally Occurring TPE-CA Maintains Gut Microbiota and Bile Acids Homeostasis via FXR Signaling Modulation of the Liver –Gut Axis
Antibiotics-induced changes in intestinal flora (dysbiosis) may have various effects on the host. Dysbiosis is associated with numerous metabolites including bile acids, which are produced in the liver from cholesterol and metabolized in the gut by intestinal microbiota. Total phenolic extracts of Citrus aurantium L. (TPE-CA) are rich in dietary flavanones and their glycosyl derivatives, including flavones, flavonols, polymethoxyflavones and coumarins, which exert positive health effects on the microbiota. The aim of this study is to elucidate the interplays between the intestinal microbiota and bile acids metabolism attri...
Source: Frontiers in Pharmacology - February 6, 2020 Category: Drugs & Pharmacology Source Type: research

A Novel C Type CpG Oligodeoxynucleotide Exhibits Immunostimulatory Activity In Vitro and Enhances Antitumor Effect In Vivo
ConclusionsHP06T07, a novel CpG-C ODN, shows potent immunostimulatory activity in vitro and suppresses tumor growth in the CT26 subcutaneous mouse model. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 6, 2020 Category: Drugs & Pharmacology Source Type: research

Ketamine Alleviates Postoperative Depression-Like Symptoms in Susceptible Mice: The Role of BDNF-TrkB Signaling
Patients are more likely to suffer from central nervous system (CNS) complications after anesthesia and surgery. However, postoperative depression (POD) has not yet received sufficient attentions, and its pathogenesis and therapeutic strategies remain poorly understood. We here aimed to investigate whether brain derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling plays an important role in POD. BDNF-TrkB signaling was altered in brain and peripheral tissues, including medial prefrontal cortex (mPFC), hippocampus, liver, and muscle, among control, POD susceptible, and resilient groups. Additiona...
Source: Frontiers in Pharmacology - February 6, 2020 Category: Drugs & Pharmacology Source Type: research

Healthcare Professionals ’ Preferred Efficacy Endpoints and Minimal Clinically Important Differences in the Assessment of New Medicines for Chronic Obstructive Pulmonary Disease
BackgroundRegistration authorities evaluate effects of new medicines for chronic obstructive pulmonary disease (COPD) on airway obstruction, dyspnea, health status and exacerbations. To establish clinical relevance, minimal clinically important differences (MCIDs) are used. The aim of this study was to investigate which efficacy endpoints and MCIDs healthcare professionals consider clinically relevant for new COPD medicines.Materials and Methods7,731 Healthcare professionals received an electronic questionnaire. Participants were asked for: 1) preferred efficacy endpoints for new COPD medicines and 2) cut-off values defini...
Source: Frontiers in Pharmacology - February 6, 2020 Category: Drugs & Pharmacology Source Type: research

Celastrol Suppresses Glioma Vasculogenic Mimicry Formation and Angiogenesis through blocking PI3K/Akt/mTOR Signalling Pathway
Angiogenesis and vasculogenic mimicry (VM) are thought to be the predominant process for tumor blood supply in the growth and metastasis of glioblastoma (GBM). Celastrol has potential anti-glioma effects, however the mechanism underlying its action remains unclarified. Recent studies showed that the signalling pathway of PI3K/Akt/ mTOR is closely related to angiogenesis and VM formation. In the present study, by the treatment of celastrol, tumor growth was suppressed, tight junction and basal lamina structures in tumor microvasculature was disarranged in U87 glioma orthotopic xenografts in nude mice. Periodic Acid Staining...
Source: Frontiers in Pharmacology - February 6, 2020 Category: Drugs & Pharmacology Source Type: research

Views of European Drug Development Stakeholders on Treatment Optimization and Its Potential for Use in Decision-Making
ConclusionsStakeholders involved in drug development consider treatment optimization studies to be valuable tools to address current evidence gaps and support their implementation into the existing research framework. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 5, 2020 Category: Drugs & Pharmacology Source Type: research

Challenges and Opportunities for Therapeutic Targeting of Calmodulin Kinase II in Heart
Heart failure remains a major health burden around the world. Despite great progress in delineation of molecular mechanisms underlying development of disease, standard therapy has not advanced at the same pace. The multifunctional signaling molecule Ca2+/calmodulin-dependent protein kinase II (CaMKII) has received considerable attention over recent years for its central role in maladaptive remodeling and arrhythmias in the setting of chronic disease. However, these basic science discoveries have yet to translate into new therapies for human patients. This review addresses both the promise and barriers to developing transla...
Source: Frontiers in Pharmacology - February 5, 2020 Category: Drugs & Pharmacology Source Type: research

Cyp2j5-Gene Deletion Affects on Acetylcholine and Adenosine-Induced Relaxation in Mice: Role of Angiotensin-II and CYP-Epoxygenase Inhibitor
Previously, we showed vascular endothelial overexpression of human-CYP2J2 enhances coronary reactive hyperemia in Tie2-CYP2J2 Tr mice, and eNOS−/− mice had overexpression of CYP2J-epoxygenase with adenosine A2A receptor-induced enhance relaxation, but we did not see the response in CYP2J-epoxygenase knockout mice. Therefore, we hypothesized that Cyp2j5-gene deletion affects acetylcholine- and 5'-N-ethylcarboxamidoadenosine (NECA) (adenosine)-induced relaxation and their response is partially inhibited by angiotensin-II (Ang-II) in mice. Acetylcholine (Ach)-induced response was tested with N-(methylsulfonyl)-2-(...
Source: Frontiers in Pharmacology - February 5, 2020 Category: Drugs & Pharmacology Source Type: research

Corrigendum: Genotype –Phenotype Association Analysis Reveals New Pathogenic Factors for Osteogenesis Imperfecta Disease
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 5, 2020 Category: Drugs & Pharmacology Source Type: research

Xiaozhang Tie Improves Intestinal Motility in Rats With Cirrhotic Ascites by Regulating the Stem Cell Factor/c-kit Pathway in Interstitial Cells of Cajal
We previously discovered that Xiaozhang Tie (XZT) was helpful for cirrhotic ascites, with obvious abdominal distention relief, suggesting that it may improve gastrointestinal (GI) motility. However, the underlying mechanisms of GI motility in cirrhotic ascites are unclear. Here, we aimed to discover explored the effect of XZT on GI motility in animal cirrhotic ascites and probed the action mechanism affecting GI motility by regulating the stem cell factor (SCF)/c-kit pathway in interstitial cells of Cajal (ICCs) and GI hormones. First, rat models of cirrhotic ascites were developed and then divided randomly into the follow...
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

Sensing Technology to Facilitate Behavioral and Psychological Symptoms and to Monitor Treatment Response in People With Dementia. A Systematic Review
ConclusionsTargeted clinical application of specific technologies is poised to revolutionize precision care in dementia as these technologies may be used both by patients and caregivers, and at a systems level to provide safe and effective care. To highlight awareness of legal regulations, data risk assessment, and patient and public involvement, we propose a necessary framework for sustainable ethical innovation in healthcare technology. The success of this field will depend on interdisciplinary cooperation and the advance in sustainable ethic innovation.Systematic Review RegistrationPROSPERO, identifier CRD42019134313. (...
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

Corilagin Alleviates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced C57BL/6 Mice by Ameliorating Oxidative Stress and Restoring Autophagic Flux
In conclusion, these results demonstrate that Cori is a potential candidate for the treatment of NAFLD via diminishing oxidative stress, restoring autophagic flux, as well as improving mitochondrial functions. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

Cell Membrane-Camouflaged Nanocarriers for Cancer Diagnostic and Therapeutic
Cell membrane (CM)-camouflaged nanocarriers (CMNPs) are the tools of a biomimetic strategy that has attracted significant attention. With a wide range of nanoparticle cores and CMs available, various creative CMNP designs have been studied for cancer diagnosis and therapy. The various functional CM molecules available allow CMNPs to demonstrate excellent properties such as prolonged circulation time, immune escape ability, reduced systemic toxicity, and homologous targeting ability when camouflaged with CMs derived from various types of natural cells including red and white blood cells, platelets, stem cells, and cancer ce...
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

Vascular Abnormalities and the Role of Vascular Endothelial Growth Factor in the Epileptic Brain
Epilepsy is a chronic neurological disorder generally defined to be caused by excessive neuronal activity. Thus, excessive neuronal activity is the main target of the currently used antiepileptic drugs (AEDs). However, as many as 30% of epileptic patients show drug resistance to currently available AEDs, which suggests that epilepsy should be attributed not only to neuronal cells but also to other brain cells, such as glial cells and vascular cells. Astrocytes, pericytes, and endothelial cells in particular comprise the blood–brain barrier (BBB), which tightly regulates the exchange of substances between the brain pa...
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

Developmental Population Pharmacokinetics and Dosing Optimization of Cefepime in Neonates and Young Infants
ConclusionA population pharmacokinetic model of cefepime in neonates and young infants was established. According to simulation results based on the developmental pharmacokinetics–pharmacodynamics, different dosage regimens should be given depending on pathogens and the postmenstrual age. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

TSG-6 Inhibits Oxidative Stress and Induces M2 Polarization of Hepatic Macrophages in Mice With Alcoholic Hepatitis via Suppression of STAT3 Activation
Tumor necrosis factor (TNF)-α-stimulated protein 6 (TSG-6) is a secreted protein with diverse tissue protective and anti-inflammatory properties. We aimed to investigate its effective in treating mice with alcoholic hepatitis (AH) and the associated mechanisms. AH was induced in 8–10 week female C57BL/6N mice by chronic-binge ethanol feeding for 10 days. Intraperitoneal (i.p.) injection of recombinant mouse TSG-6 or saline were performed in mice on day 10. Blood samples and hepatic tissues were collected on day 11. Biochemistry, liver histology, flow cytometry, and cytokine measurements were conducted. Compared...
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

Immune Challenges and Seizures: How Do Early Life Insults Influence Epileptogenesis?
The development of epilepsy, a process known as epileptogenesis, often occurs later in life following a prenatal or early postnatal insult such as cerebral ischemia, stroke, brain trauma, or infection. These insults share common pathophysiological pathways involving innate immune activation including neuroinflammation, which is proposed to play a critical role in epileptogenesis. This review provides a comprehensive overview of the latest preclinical evidence demonstrating that early life immune challenges influence neuronal hyperexcitability and predispose an individual to later life epilepsy. Here, we consider the range ...
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

The Efficacy of Berberine-Containing Quadruple Therapy on Helicobacter Pylori Eradication in China: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
ConclusionsThe analysis showed that the addition of berberine in standard triple therapy could improve Helicobacter pylori eradication rate and clinical symptom remission rate, accelerate ulcer healing, and reduce adverse events, which is very beneficial to clinical work in China. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

Alpha-Glucosidase Inhibitors Alter Gut Microbiota and Ameliorate Collagen-Induced Arthritis
Acarose is an anti-diabetic drug and exhibits anti-arthritic effects. We hypothesized that acarbose influences the gut microbiota to affect the course of arthritis and tested this hypothesis in a collagen-induced arthritis (CIA) murine model. Acarbose in drinking water was administered via gastric gavage started prior to or at the time of CIA induction. Gut microbiota were evaluated with 16S rRNA gene sequencing from fecal pellets collected prior to arthritis induction, during onset of arthritis, and after treatment. Immune response was evaluated by measuring changes in T helper-17 (Th17) and T regulatory (Treg) cells in t...
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

Progress in Genetic Polymorphisms Related to Lipid Disturbances Induced by Atypical Antipsychotic Drugs
Metabolic side effects such as weight gain and disturbed lipid metabolism are often observed in the treatment of atypical antipsychotic drugs (AAPDs), which contribute to an excessive prevalence of metabolic syndrome among schizophrenic patients. Great individual differences are observed but the underlying mechanisms are still uncertain. Research on pharmacogenomics indicates that gene polymorphisms involved in the pathways controlling food intake and lipid metabolism may play a significant role. In this review, relevant genes (HTR2C, DRD2, LEP, NPY, MC4R, BDNF, MC4R, CNR1, INSIG2, ADRA2A) and genetic polymorphisms related...
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

Edible Bird ’s Nest Protects Against Hyperglycemia-Induced Oxidative Stress and Endothelial Dysfunction
Increased oxidative stress by hyperglycemia is a major cause of vascular complications in diabetes. Bird’s nest, which is made from the saliva of swiftlets has both medicinal and nutritional values dated back to ancient China. However, its role in improving endothelial dysfunction due to diabetes is yet to be elucidated. The present study examined the protective effect and mechanism of action of the aqueous extract of hydrolyzed edible bird nest (HBN) on endothelium in models of diabetes, in vitro and in vivo. Male db/m+ and db/db mice were orally administered with or without HBN and glibenclamide for 28 days, follow...
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

Role of Estrogen Receptors α and β in a Murine Model of Asthma: Exacerbated Airway Hyperresponsiveness and Remodeling in ERβ Knockout Mice
In this study, we evaluated the receptor specific effect of circulating endogenous estrogen in regulating AHR and remodeling using ERα and ERβ knockout (KO) mice. C57BL/6J WT, ERα KO, and ERβ KO mice were challenged intranasally with a mixed-allergen (MA) or PBS. Lung function was measured using flexiVent followed by collection of broncho-alveolar lavage fluid for differential leukocyte count (DLC), histology using hematoxylin and eosin (H&E) and Sirius red-fast green (SRFG) and detecting αsmooth muscle actin (α-SMA), fibronectin and vimentin expression using immunofluorescence (IF). R...
Source: Frontiers in Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Source Type: research

MicroRNA-96 Promotes Vascular Repair in Oxygen-Induced Retinopathy —A Novel Uncovered Vasoprotective Function
ConclusionThis study demonstrates that miR-96 regulates the expression of angiogenic factors (VEGF/ANG-2) associated to the maintenance of retinal and choroidal microvasculature during physiological and pathological conditions. Intravitreal supplementation of miR-96 mimic could constitute a novel therapeutic strategy to improve vascular repair in OIR and other ischemic retinopathies. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 3, 2020 Category: Drugs & Pharmacology Source Type: research

Physiologically Based Pharmacokinetic Modeling to Understand the Absorption of Risperidone Orodispersible Film
ConclusionThe main absorption route for risperidone ODF was the gastrointestine. The absorption percentage via oral mucosa was almost negligible due to the physicochemical properties of risperidone although ODF dissolved completely in the oral cavity of Beagle dogs within 2 min. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 3, 2020 Category: Drugs & Pharmacology Source Type: research