Ascorbic Acid Sensitizes Colorectal Carcinoma to the Cytotoxicity of Arsenic Trioxide via Promoting Reactive Oxygen Species-Dependent Apoptosis and Pyroptosis
Arsenic trioxide (ATO) is an effective therapeutic agent against acute promyelocytic leukemia (APL); however, its anti-tumor effect on solid tumors such as colorectal cancer (CRC) is still in debate. Ascorbic acid (AA) also produces a selective cytotoxic activity against tumor cells. Here, we exploit the potential benefit of ATO/AA combination in generating cytotoxicity to CRC cells, which may lay the groundwork for the potential combinational chemotherapy of CRCs. According to the results, we found that ATO and AA effectively inhibited the viability of human CRC cells in a synergistic manner. AA and ATO corporately activa...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Roles and Mechanisms of Hawthorn and Its Extracts on Atherosclerosis: A Review
Cardiovascular disease (CVD), especially atherosclerosis, is a leading cause of morbidity and mortality globally; it causes a considerable burden on families and caregivers and results in significant financial costs being incurred. Hawthorn has an extensive history of medical use in many countries. In China, the use of hawthorn for the treatment of CVD dates to 659 AD. In addition, according to the theory of traditional Chinese medicine, it acts on tonifying the spleen to promote digestion and activate blood circulation to dissipate blood stasis. This review revealed that the hawthorn extracts possess serum lipid-lowering,...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

The Regulator of G Protein Signaling Homologous Domain of G Protein-Coupled Receptor Kinase 2 Mediates Short-Term Desensitization of β3-Adrenergic Receptor
G protein coupled receptor (GPCR) kinases (GRKs) are key regulators of GPCR signaling. Canonical mechanism of GPCR desensitization involves receptor phosphorylation by GRKs followed by arrestin recruitment and uncoupling from heterotrimeric G protein. Although β3-adrenergic receptor (β3AR) lacks phosphorylation sites by GRKs, agonist treatment proved to induce β3AR desensitization in many cell types. Here we show that GRK2 mediates short-term desensitization of β3AR by a phosphorylation independent mechanism but mediated by its domain homologous to the regulator of G protein signaling (RGS). HEK293T cel...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Toddalolactone Protects Lipopolysaccharide-Induced Sepsis and Attenuates Lipopolysaccharide-Induced Inflammatory Response by Modulating HMGB1-NF- κB Translocation
Toddalolactone (TA-8) is a main compound isolated from Toddalia asiatica (L.) Lam., and its anti-inflammatory activity and anti-inflammatory mechanism are less studied. In the present study, we investigated the anti-inflammatory effects of TA-8. Our experimental results showed that TA-8 inhibited the production of pro-inflammatory cytokines by both lipopolysaccharide (LPS)-activated RAW 264.7 cells and septic mice. Moreover, TA-8 suppressed the NF-κB transcriptional activity, reduced the nuclear translocation and phosphorylation of NF-κB, blocked the translocation of HMGB1 from the nucleus to cytosol, and decre...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn ’s Disease Development via the Upregulation of CARD3 Expression
There is increasing evidence that members of the gut microbiota, especially Fusobacterium nucleatum (F. nucleatum), are associated with Crohn’s disease (CD), but the specific mechanism by which F. nucleatum promotes CD development is unclear. Here, we first examined the abundance of F. nucleatum and its effects on CD disease activity and explored whether F. nucleatum aggravated intestinal inflammation and promoted intestinal mucosal barrier damage in vitro and in vivo. Our data showed that F. nucleatum was enriched in 41.21% of CD tissues from patients and was correlated with the clinical course, clinical activity, a...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Xuebijing Injection Alleviates Pam3CSK4-Induced Inflammatory Response and Protects Mice From Sepsis Caused by Methicillin-Resistant Staphylococcus aureus
In conclusion, our findings demonstrated that XBJ played a protective role in MRSA-challenged mice and down-regulated the inflammatory response and the activation of signaling pathways initiated by Pam3CSK4. It enlarged the clinical application of XBJ in the treatment of severe bacterial infection, e.g. caused by MRSA. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Pleiotropic Effects of Simvastatin on the Regulation of Potassium Channels in Monocytes
ConclusionOur data suggested Kv1.3 in monocytes was a potential molecular target of the pleiotropic effects of statins. KCa3.1 might be another marker of CAD, but not associated with statins treatment. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Brozopine Inhibits 15-LOX-2 Metabolism Pathway After Transient Focal Cerebral Ischemia in Rats and OGD/R-Induced Hypoxia Injury in PC12 Cells
In conclusion, BZP exerted protective effects against cerebral ischemia via inhibition of 15-LOX-2 activity. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

The P2X7 Receptor 489C > T Gain of Function Polymorphism Favors HHV-6A Infection and Associates With Female Idiopathic Infertility
The P2X7 receptor (P2X7R) is an ATP-gated ion channel known for its proinflammatory activity. Despite its participation in host defense against pathogens, the role played in viral infections, notably those caused by herpes viruses, has been seldom studied. Here we investigated the effect of P2X7R expression on human herpes virus 6 A (HHV-6A) infection of P2X7R-expressing HEK293 cells. We show that functional P2X7R increases while its blockade decreases viral load. Interestingly, HHV-6A infection was enhanced in HEK293 cells transfected with P2X7R cDNA bearing the gain of function 489C>T SNP (rs208294, replacing a histid...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Perindopril Improves Cardiac Function by Enhancing the Expression of SIRT3 and PGC-1 α in a Rat Model of Isoproterenol-Induced Cardiomyopathy
In this study, to investigate the mechanisms of PER in cardiac protection, a rat model of cardiomyopathy was established by continuous isoproterenol (ISO) stimulation. Changes in the body weight, heart weight index, echocardiography, histological staining, mitochondrial microstructure, and biochemical indicators were examined. Our results demonstrate that PER reduced myocardial remodeling, inhibited deterioration of cardiac function, and delayed HF onset in rats with ISO-induced cardiomyopathy. PER markedly reduced reactive oxygen species (ROS) production, increased the levels of antioxidant enzymes, inhibited mitochondria...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Preventive Effects of Dulaglutide on Disuse Muscle Atrophy Through Inhibition of Inflammation and Apoptosis by Induction of Hsp72 Expression
Pathological conditions such as joint immobilization, long-time bed rest, or inactivity may result in disuse-induced muscle wasting and dysfunction. To investigate the effect of dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist, on disuse muscle atrophy, disuse condition was induced by spiral wire immobilization in C57BL/6 mice and the mice were treated with dulaglutide. Dulaglutide treatment effectively improved muscle function and increased muscle mass compared with vehicle treatment. Dulaglutide inhibited the decrease of muscle fiber size and the expression of atrophic factors such as myostatin, atrogi...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Eugenol Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Autophagy via AMPK-mTOR-P70S6K Pathway
In conclusion, pretreatment with eugenol attenuated cerebral I/R injury by inducing autophagy via AMPK/mTOR/P70S6K signaling pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Morphine Addiction and Oxidative Stress: The Potential Effects of Thioredoxin-1
In conclusion, Trx-1 may be very promising for clinical therapy of morphine addiction in the future. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Sphingosine-1-Phosphate Receptors Modulators Decrease Signs of Neuroinflammation and Prevent Parkinson ’s Disease Symptoms in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model
Sphingosine-1-phosphate (S1P) is a potent bioactive lipid mediator that acts as a natural ligand upon binding to five different receptors that are located in astrocytes, oligodendrocytes, microglial and neuronal cells. Recently, global activation of these receptors by FTY720 (fingolimod) has been suggested to provide neuroprotection in animal model of Parkinson’s disease (PD). Among S1P receptors, the subtype 1 (S1P1R) has been linked to features of neuroprotection and, using the selective agonist SEW2871, the present investigation assessed potential benefits (and mechanisms) of this receptor subtype in an establishe...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

The Protective Effect of Basic Fibroblast Growth Factor on Diabetic Nephropathy Through Remodeling Metabolic Phenotype and Suppressing Oxidative Stress in Mice
This study aimed to investigate the therapeutic effect of basic fibroblast growth factor (bFGF) in db/db mice with diabetic nephropathy and explore its possible metabolic mechanisms using a nuclear magnetic resonance-based metabolomic approach. We found that bFGF treatment significantly alleviate urinary albumin to creatinine ratio and renal fibrosis in db/db mice, suggesting a potential renal protective effect. Metabolomics results reveal that bFGF remodeled metabolic phenotypes of the kidney and urine in db/db mice, mainly involving energy metabolism, methylamine metabolism, osmoregulation, and oxidative stress. Furtherm...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Long-Term Toxicity Study of Topical Administration of a Highly-Stable rh-aFGF Carbomer 940 Hydrogel in a Rabbit Skin Wound Model
This study aimed to reveal toxicity target organs and the toxicity dose-response in the long-term administration of rh-aFGF carbomer 940 hydrogel in a rabbit skin wound model. New Zealand rabbits were topically administrated rh-aFGF carbomer 940 hydrogel at a daily dose of 900 IU/cm2, 1,800 IU/cm2, and 3,600 IU/cm2 for 28 days. Lyophilized rh-aFGF agent was used as the positive control group. General behavior, serum chemistry, skin irritation, immunogenicity, immunotoxicity, and histopathology were analyzed at designated time points. Results revealed that food intake, body weight, body temperature, heart rate, and eye exam...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Implementation of Health Technology Assessment in the Middle East and North Africa: Comparison Between the Current and Preferred Status
Discussion group members helped to validate key conclusions during and after the conference.ResultsHealth policy experts in MENA countries would like to facilitate HTA implementation and expect significant changes with some generalizable directions in 10 years compared to the current status according. HTA capacity building has to be strengthened by more graduate and postgraduate programs. Increased public budget and enhanced institutionalization are necessary success factors of HTA implementation. The scope of HTA has to be extended from pharmaceuticals to non-pharmaceutical technologies and to revision of previous policy ...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Large Sample Size Fallacy in Trials About Antipsychotics for Neuropsychiatric Symptoms in Dementia
ConclusionSample size calculations were poorly reported in antipsychotic trials for dementia. Placebo-controlled trials of atypical antipsychotics showed large sample size fallacy while head-to-head trials were massively underpowered. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

An Updated Review of Randomized Clinical Trials Testing the Improvement of Cognitive Function of Ginkgo biloba Extract in Healthy People and Alzheimer ’s Patients
Alzheimer’s disease (AD) is a common neurodegenerative disease, mainly manifested by cognitive dysfunction. It seriously reduces the quality of life, and there is no ideal treatment strategy in clinical practice. Clinical studies on the treatment of AD with Ginkgo biloba L. leaf extract (EGb) have been reported since 1980s, and many clinical studies have been carried out during the following 30 years. However, the benefits of EGb on the treatment of AD are still controversial. In this review, we collected the clinical trial reports of EGb on cognitive function from Pubmed, Elsevier, Europe PMC, and other database sin...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine
Cystic fibrosis (CF) is a lethal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which result in impairment of CFTR mRNA and protein expression, function, stability or a combination of these. Although CF leads to multifaceted clinical manifestations, the respiratory disorder represents the major cause of morbidity and mortality of these patients. The life expectancy of CF patients has substantially lengthened due to early diagnosis and improvements in symptomatic therapeutic regimens. Quality of life remains nevertheless limited, as these individuals are subjected to conside...
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

Neuroprotective Effects of Qingnao Dripping Pills Against Cerebral Ischemia via Inhibiting NLRP3 Inflammasome Signaling Pathway: In Vivo and In Vitro
In conclusion, QNDP had neuroprotective effects against cerebral ischemia via inhibiting NLRP3 inflammasome signaling pathway, and was a potential candidate for the future treatment of ischemic stroke. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 20, 2020 Category: Drugs & Pharmacology Source Type: research

A Method for Predicting Hemolytic Potency of Chemically Modified Peptides From Its Structure
In the present study, a systematic effort has been made to predict the hemolytic potency of chemically modified peptides. All models have been trained, tested, and evaluated on a dataset that contains 583 modified hemolytic peptides and a balanced number of non-hemolytic peptides. Machine learning techniques have been used to build the classification models using an immense range of peptide features that include 2D, 3D descriptors, fingerprints, atom, and diatom compositions. Random Forest based model developed using fingerprints as an input feature achieved maximum accuracy of 78.33% with AUC of 0.86 on the main dataset a...
Source: Frontiers in Pharmacology - February 20, 2020 Category: Drugs & Pharmacology Source Type: research

New Insights About Doxorubicin-Induced Toxicity to Cardiomyoblast-Derived H9C2 Cells and Dexrazoxane Cytoprotective Effect: Contribution of In Vitro1H-NMR Metabonomics
The objective of the present work was to study from a metabolic point of view the side effects of DOX and the protective properties of DEX. In vitro1H-NMR metabonomics was applied to the rat cardiomyoblastic H9C2 cell line. This strategy was used with the hope of unveiling possible new targets to cope with DOX cardiotoxicity. Another underlying goal was the validation of H9C2 in vitro model for metabolic investigations of DOX and DEX effects. For this purpose, several parameters, including oxidative stress, cell mortality, and apoptosis, were measured to assess the effects of DOX and DEX alone or in combination. The metabo...
Source: Frontiers in Pharmacology - February 20, 2020 Category: Drugs & Pharmacology Source Type: research

Theranostic Attributes of Acoustic Cluster Therapy and Its Use for Enhancing the Effectiveness of Liposomal Doxorubicin Treatment of Human Triple Negative Breast Cancer in Mice
In this study we investigated the therapeutic efficacy of ACT with liposomal doxorubicin for the treatment of triple negative breast cancer using orthotopic human tumor xenografts (MDA-MB-231-H.luc) in athymic mice (ICR-NCr-Foxn1nu). Doxil® (6 mg/kg, i.v.) was administered at days 0 and 21, each time immediately followed by three sequential ACT (20 ml/kg PS101) treatment procedures (n = 7–10). B-mode and nonlinear ultrasound images acquired during the activation phase were correlated to the therapeutic efficacy.ResultsResults show that combination with ACT induces a strong increase in the therapeutic efficacy of ...
Source: Frontiers in Pharmacology - February 20, 2020 Category: Drugs & Pharmacology Source Type: research

Association of Disease Knowledge and Medication Adherence Among Out-Patients With Type 2 Diabetes Mellitus in Khobar, Saudi Arabia
ObjectiveThe study aimed to evaluate the association between disease knowledge and medication adherence in patients with type 2 diabetes mellitus.MethodsA cross-sectional study was conducted for three months, in patients with type 2 diabetes who visited three community pharmacies located in Khobar, Saudi Arabia. Patients’ disease knowledge and their adherence to medications were documented using Arabic versions of the Michigan Diabetes Knowledge Test and the General Medication Adherence Scale respectively. Data were analyzed through SPSS version 23. Chi-square test was used to report association of demographics with ...
Source: Frontiers in Pharmacology - February 20, 2020 Category: Drugs & Pharmacology Source Type: research

Characterization and Neuroprotection Potential of Seleno-Polymannuronate
Seleno-polymannuronate (Se-PM) was prepared from alginate-derived polymannuronate (PM) through a sulfation followed by a selenylation replacement reaction. The organic selenium content of Se-PM was 437.25 μg/g and its average molecular weight was 2.36 kDa. The neuroprotection effect of Se-PM and corresponding molecular mechanisms were investigated. Our results showed that, comparing to both sulfated PM (S-PM) and PM, Se-PM remarkably inhibited the aggregation of Aβ1–42 oligomer in vitro and significantly reduced the APP and BACE1 protein expression in N2a-sw cells, highlighting the critical function of the se...
Source: Frontiers in Pharmacology - February 20, 2020 Category: Drugs & Pharmacology Source Type: research

Synergistic Effect of Rubus crataegifolius and Ulmus macrocarpa Against Helicobacter pylori Clinical Isolates and Gastritis
This study aimed to evaluate synergistic effect of Rubus crataegifolius (RF) and Ulmus macrocarpa Hance (UL) against H. pylori. Antibacterial susceptibility of each extract either separately or in combination was studied against two H. pylori standard strains and 11 clinical isolates using agar dilution method. The effect of the extracts on H. pylori inoculated Balb/c mice model was also studied using single dosing (100 mg/kg each) approach. The MIC50 of RF and UL were more than 100 and 200 µg/ml, respectively, against the tested strains. However, simultaneous treatment with RF and UL at 75 and 50 µg/ml, respec...
Source: Frontiers in Pharmacology - February 20, 2020 Category: Drugs & Pharmacology Source Type: research

Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Are a Heterogeneous Population That Demonstrate Rapid Culture-Induced Changes
Human adipose-derived mesenchymal stromal cells (ASC) are showing clinical promise for the treatment of a range of inflammatory and degenerative conditions. These lipoaspirate-derived cells are part of the abundant and accessible source of heterogeneous stromal vascular fraction (SVF). They are typically isolated and expanded from the SVF via adherent cell culture for at least 2 weeks and as such represent a relatively undefined population of cells. We isolated ex vivo ASC directly from lipoaspirate using a cocktail of antibodies combined with immunomagnetic bead sorting. This method allowed for the rapid enrichment of a d...
Source: Frontiers in Pharmacology - February 20, 2020 Category: Drugs & Pharmacology Source Type: research

No Major Effect of Innate Immune Genetics on Acute Kidney Rejection in the First 2 Weeks Post-Transplantation
ConclusionsThis study did not detect any statistically significant effects of recipient or donor innate immune genetics on acute rejection incidence in the first 2 weeks post-transplantation. However, the sample size was small, and future larger studies or meta-analyses are required to demonstrate conclusively if innate immune genetics such as IL6 influence the risk of acute rejection after kidney transplantation. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 20, 2020 Category: Drugs & Pharmacology Source Type: research

Editorial: Nocebo Effects and Their Influence on Clinical Trials and Practice: Modulating Factors in Healthy and Pathological Conditions
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 19, 2020 Category: Drugs & Pharmacology Source Type: research

Corrigendum: Progression and Regression of Hepatic Lesions in a Mouse Model of NASH Induced by Dietary Intervention and Its Implications in Pharmacotherapy
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 19, 2020 Category: Drugs & Pharmacology Source Type: research

Hydrogen-Deuterium Exchange Mass-Spectrometry of Secondary Active Transporters: From Structural Dynamics to Molecular Mechanisms
Membrane transporters allow the selective transport of otherwise poorly permeable solutes across the cell membrane and thus, play a key role in maintaining cellular homeostasis in all kingdoms of life. Importantly, these proteins also serve as important drug targets. Over the last decades, major progress in structural biology methods has elucidated important structure-function relationships in membrane transporters. However, structures obtained using methods such as X-ray crystallography and high-resolution cryogenic electron microscopy merely provide static snapshots of an intrinsically dynamic, multi-step transport proce...
Source: Frontiers in Pharmacology - February 19, 2020 Category: Drugs & Pharmacology Source Type: research

Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK Rats
This study aims to investigate whether HIF-1/BNIP3-mediated mitochondrial autophagy is involved in the restoration of sevoflurane postconditioning cardioprotection in diabetic state. Ischemia/reperfusion (I/R) model was established by ligating the anterior descending coronary artery and sevoflurane was administered at the first 15 min of reperfusion. Myocardial infarct size, mitochondrial ultrastructure and autophagosome, ATP content, mitochondrial membrane potential, ROS production, HIF-1α, BNIP3, LC3B-II, Beclin-1, P62, LAMP2 protein expression were detected 2 h after reperfusion, and cardiac function was evaluated...
Source: Frontiers in Pharmacology - February 19, 2020 Category: Drugs & Pharmacology Source Type: research

Applying Machine Learning to Ultrafast Shape Recognition in Ligand-Based Virtual Screening
In this study we explore the use of suitable Machine Learning techniques that can be trained using USR descriptors, so as to improve the similarity detection of potential new leads. We use molecules from the Directory for Useful Decoys-Enhanced to construct machine learning models based on three different algorithms: Gaussian Mixture Models (GMMs), Isolation Forests and Artificial Neural Networks (ANNs). We train models based on full molecule conformer models, as well as the Lowest Energy Conformations (LECs) only. We also investigate the performance of our models when trained on smaller datasets so as to model virtual scr...
Source: Frontiers in Pharmacology - February 19, 2020 Category: Drugs & Pharmacology Source Type: research

Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway
This study investigated the neuroprotective effect of stachydrine. Male Sprague-Dawley (SD) rats were randomly divided into sham, control, and stachydrine groups. The neurological deficit score was evaluated and the infarct size of the brain was measured using 2,3,5-triphenyltetra-zolium (TTC) chloride staining assay, and the pathological changes in the brain tissues were examined by HE staining. Nissl and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) staining were performed to assess the numbers of Nissl bodies and the levels of apoptosis in the neurons. The activities of supero...
Source: Frontiers in Pharmacology - February 18, 2020 Category: Drugs & Pharmacology Source Type: research

Crosstalk Between Kappa Opioid and Dopamine Systems in Compulsive Behaviors
The strength of goal-oriented behaviors is regulated by midbrain dopamine neurons. Dysfunctions of dopaminergic circuits are observed in drug addiction and obsessive-compulsive disorder. Compulsive behavior is a feature that both disorders share, which is associated to a heightened dopamine neurotransmission. The activity of midbrain dopamine neurons is principally regulated by the homeostatic action of dopamine through D2 receptors (D2R) that decrease the firing of neurons as well as dopamine synthesis and release. Dopamine transmission is also regulated by heterologous neurotransmitter systems such as the kappa opioid sy...
Source: Frontiers in Pharmacology - February 18, 2020 Category: Drugs & Pharmacology Source Type: research

Contrasting Effects of Adipokines on the Cytokine Production by Primary Human Bronchial Epithelial Cells: Inhibitory Effects of Adiponectin
ConclusionsThe APN concentrations are abnormally low in obese individuals, and this fall may contribute to the susceptibility to viral lung infections and the severity of these infections in obese individuals. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 18, 2020 Category: Drugs & Pharmacology Source Type: research

Phytopharmacology and Clinical Updates of Berberis Species Against Diabetes and Other Metabolic Diseases
The incidences of diabetic mellitus and other metabolic diseases such as hypertension and hyperlipidemia are increasing worldwide; however, the current treatment is not able to control the rapidly increasing trend in diabetes mortality and morbidity. Studies related to the effectiveness of extracts and pure compounds obtained from plants have shown promising responses in preclinical and clinical studies related to these metabolic diseases. Plants belonging to the genus Berberis (Family: Berberidaceae) are widely distributed with nearly 550 species worldwide. Extracts and compounds obtained from Berberis species, especially...
Source: Frontiers in Pharmacology - February 18, 2020 Category: Drugs & Pharmacology Source Type: research

Jianpi Huayu Decoction Attenuates the Immunosuppressive Status of H22 Hepatocellular Carcinoma-Bearing Mice: By Targeting Myeloid-Derived Suppressor Cells
Tumor-induced immunosuppressive microenvironment in which myeloid-derived suppressor cells (MDSCs) plays an important role, remains an obstacle for effective oncotherapy currently. Inducing MDSCs into maturation was confirmed as an effective method to reduce the tumor-bearing host's immunosuppression. Traditional Chinese medicines (TCM) possess characteristics of alleviating immunosuppression of cancer patients and low toxicity. Jianpi Huayu Decoction (JHD) was an experienced formula of TCM for oncotherapy based on TCM theory and clinical practice. We previously observed that JHD attenuated the expression of interleukin-10...
Source: Frontiers in Pharmacology - February 18, 2020 Category: Drugs & Pharmacology Source Type: research

Ethnopharmacological Applications Targeting Alcohol Abuse: Overview and Outlook
Excessive alcohol consumption is the cause of several diseases and thus is of a major concern for society. Worldwide alcohol consumption has increased by many folds over the past decades. This urgently calls for intervention and relapse counteract measures. Modern pharmacological solutions induce complete alcohol self-restraint and prevent relapse, but they have many side effects. Natural products are most promising as they cause fewer adverse effects. Here we discuss in detail the medicinal plants used in various traditional/folklore medicine systems for targeting alcohol abuse. We also comprehensively describe preclinica...
Source: Frontiers in Pharmacology - February 15, 2020 Category: Drugs & Pharmacology Source Type: research

Development of Prediction Models for Drug-Induced Cholestasis, Cirrhosis, Hepatitis, and Steatosis Based on Drug and Drug Metabolite Structures
In this study, we developed binary classification models to predict drug-induced cholestasis, cirrhosis, hepatitis, and steatosis based on the structure of drugs and their metabolites. DILI-positive data was obtained from post-market reports of drugs and DILI-negative data from DILIrank, a database curated by the Food and Drug Administration (FDA). Support vector machine (SVM) and random forest (RF) were used in developing models with nine fingerprints and one 2D molecular descriptor calculated from drug (152 DILI-positives and 102 DILI-negatives) and drug metabolite (192 DILI-positives and 126 DILI-negatives) structures. ...
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research

Public Knowledge, Attitude, and Practice on Herbal Remedies Used During Pregnancy and Lactation in West Bank Palestine
This study is of great importance in order to decrease the possibility of endangering the lives of fetuses and infants. A combined effort among researchers, scientists, lactating women, and pregnant women may help in changing wrong uses and thoughts about medicinal plants and help to improve the overall health of both mother and fetus. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research

Phenolic Profile and Bioactivities of Sideritis perfoliata L.: The Plant, Its Most Active Extract, and Its Broad Biological Properties
Sideritis, also named “ironwort,” “mountain tea,” or “shepherd's tea,” is a genus of flowering plants used as herbal medicine in traditional Mediterranean-area medicine systems, and these plants are generally consumed as a herbal tea. Its use as herbal tea and in traditional herbal medicine is quite popular. There are currently few studies on Sideritis perfoliata L., and only one reports the use of a liquid chromatography coupled to diode array detection and electrospray ionization tandem mass spectrometry (LC-DAD-ESI-MSn) profile and the content of phenolic compounds without considering...
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research

Editorial: Targeting Monocytes/Macrophages to Treat Atherosclerotic Inflammation
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research

Cytochrome P450-Based Drug-Drug Interactions of Vonoprazan In Vitro and In Vivo
This study was conducted both in vitro and in vivo. In the in vitro study of rat liver microsomes, ultra-performance liquid chromatography coupled to tandem mass spectrometry was utilized to assess the reversible inhibition of cytochrome P450 by vonoprazan by determining the concentration of probe drugs (phenacetin, bupropion, tolbutamide, dextromethorphan, midazolam, chlorzoxazone). The differences in the levels of probe drugs between the rat groups with or without vonoprazan administration were also tested in the rats.ResultsIn vitro analysis revealed that the IC50 values of midazolam, tolbutamide, dextromethorphan, and ...
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research

Role of Platelet-Derived Growth Factor (PDGF) in Asthma as an Immunoregulatory Factor Mediating Airway Remodeling and Possible Pharmacological Target
Asthma is a chronic and heterogenic disease of the respiratory system, one of the most common lung diseases worldwide. The underlying pathologies, which are chronic inflammatory process and airway remodeling (AR), are mediated by numerous cells and cytokines. Particularly interesting in this field is the platelet-derived growth factor (PDGF), one of the members of the human growth factor family. In this article, the authors analyze the available data on the role of PDGF in asthma in experimental models and in human research. PDGF is expressed in airway by various cells contributing to asthma pathogenesis—mast cells, ...
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research

Alleviation of Synovial Inflammation of Juanbi-Tang on Collagen-Induced Arthritis and TNF-Tg Mice Model
In this study, we found that a traditional Chinese decoction, Juanbi-Tang (JBT), JBT attenuated the symptoms of collagen-induced arthritis (CIA) mice and in tumor necrosis factor transgenic (TNF-Tg) mice by attenuating the arthritis index and hind paw thickness. According to histopathological staining of ankle sections, JBT significantly decreased the area of inflammation and reduced bone destruction of ankle joints in both these two types of mice. Moreover, decreased tartaric acid phosphatase-positive osteoclasts were observed in the JBT group compared with those found in the control group. We also revealed that JBT suppr...
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research

Comparative Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Advanced Cancer: A Systematic Review and Meta-Analysis
ConclusionNIVO + IPI is more effective than NIVO alone for the treatment of advanced cancer and can significantly improve ORR and DCR and prolong mPFS. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to validate the above conclusions. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research

Evaluation of the Developmental Toxicity Induced by E804 in Zebrafish Embryos
In this study, we investigated the toxicity of E804 on the developments of zebrafish embryos. Our results showed that E804 treatment caused a significant increase of the malformation rate compared with the control groups. Pericardial edema and curved body shape were the most morphological abnormalities observed in E804-treated group. The hatching rates and body length of the zebrafish larvae was significantly decreased in E804-treated groups. E804 also affect the development of heart, liver, phagocytes and vascular formation. Further studies showed that the level of reactive oxygen species was significantly increased. The ...
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research

Combination of Rapamycin and MK-2206 Induced Cell Death via Autophagy and Necroptosis in MYCN-Amplified Neuroblastoma Cell Lines
This study delineates the role of MYCN in the cell death induced by combination treatment of rapamycin and MK-2206 in MYCN-amplified NB cells. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research