Dexmedetomidine Improves Cardiovascular and Ventilatory Outcomes in Critically Ill Patients: Basic and Clinical Approaches
Dexmedetomidine (DEX) is a highly selective α2-adrenergic agonist with sedative and analgesic properties, with minimal respiratory effects. It is used as a sedative in the intensive care unit and the operating room. The opioid-sparing effect and the absence of respiratory effects make dexmedetomidine an attractive adjuvant drug for anesthesia in obese patients who are at an increased risk for postoperative respiratory complications. The pharmacodynamic effects on the cardiovascular system are known; however the mechanisms that induce cardioprotection are still under study. Regarding the pharmacokinetics properties, t...
Source: Frontiers in Pharmacology - February 28, 2020 Category: Drugs & Pharmacology Source Type: research

A Compartmentalized Reduction in Membrane-Proximal Calmodulin Reduces the Immune Surveillance Capabilities of CD8+ T Cells in Head and Neck Cancer
The limited ability of cytotoxic CD8+ T cells to infiltrate solid tumors and function within the tumor microenvironment presents a major roadblock to effective immunotherapy. Ion channels and Ca2+-dependent signaling events control the activity of T cells and are implicated in the failure of immune surveillance in cancer. Reduced KCa3.1 channel activity mediates the heightened inhibitory effect of adenosine on the chemotaxis of circulating T cells from head and neck squamous cell carcinoma (HNSCC) patients. Herein, we conducted experiments that elucidate the mechanisms of KCa3.1 dysfunction and impaired chemotaxis in HNSCC...
Source: Frontiers in Pharmacology - February 28, 2020 Category: Drugs & Pharmacology Source Type: research

A Review of the Anti-Inflammatory Effects of Rosmarinic Acid on Inflammatory Diseases
This article mainly describes the preclinical research of RosA on inflammatory diseases and depicts a small amount of clinical research data. The purpose of this review is to discuss the anti-inflammatory effects of RosA in inflammatory diseases and its underlying mechanism. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 28, 2020 Category: Drugs & Pharmacology Source Type: research

Corrigendum: An Improved Enzyme-Linked Focus Formation Assay Revealed Baloxavir Acid as a Potential Antiviral Therapeutic Against Hantavirus Infection
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

Low Level Antibodies Against Alpha-Tropomyosin Are Associated With Increased Risk of Coronary Heart Disease
ObjectiveNatural autoantibodies have been implicated to play a key role in the pathogenesis of coronary heart disease (CHD) because they augment autoimmune activation. The aim of this study was to identify novel specific autoantibodies of CHD, and analyze the relationship between their levels and CHD risk indicators.Approach and ResultsFirst, clinical data and sera from CHD patients were collected. Then, one protein microarray containing 37 proteins that represent candidate autoantigens was developed. The arrays were used to profile autoantibodies in randomly selected sera from 35 samples (20 CHD patients, and 15 healthy c...
Source: Frontiers in Pharmacology - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

The Clinical Pharmacist-Led Consultation for Infectious Diseases in Guizhou Province, China: A Survey Among Hospital Pharmacies
ConclusionCPC adoption is gradually increasing among hospitals and will be a promising intervention for ID treatment at grassroots medical institutions in Guizhou Province. Training more clinical pharmacists to specialize in ID, respiratory, or general diseases might be the most practical measure to promote the development of CPC for ID. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

Local Irradiation Modulates the Pharmacokinetics of Metabolites in 5-Fluorouracil —Radiotherapy–Pharmacokinetics Phenomenon
BackgroundThe effects of radiotherapy (RT) on the pharmacokinetics (PK) of 5-FU and 5-fluoro-5,6-dihydro-uracil (5-FDHU) were investigated by animal experiments.MethodsWhole-pelvis RT with 0.5 and 2 Gy was delivered to Sprague–Dawley rats. 5-FU at 100 mg/kg was intravenously infused 24 h after radiation. The pharmacokinetics of 5-FU and 5-FDHU in the plasma and bile system were calculated.ResultsThe areas under the concentration versus time curve (AUC) of 5-FU in the plasma were reduced by local irradiation by 23.7% at 0.5 Gy (P
Source: Frontiers in Pharmacology - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

Single Cell Transcriptome in Colorectal Cancer —Current Updates on Its Application in Metastasis, Chemoresistance and the Roles of Circulating Tumor Cells
Colorectal cancer (CRC) is among the most common cancer worldwide, a challenge for research, and a model for studying the molecular mechanisms involved in its development. Previously, bulk transcriptomics analyses were utilized to classify CRC based on its distinct molecular and clinicopathological features for prognosis and diagnosis of patients. The introduction of single-cell transcriptomics completely turned the table by enabling the examination of the expression levels of individual cancer cell within a single tumor. In this review, we highlighted the importance of these single-cell transcriptomics analyses as well as...
Source: Frontiers in Pharmacology - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

Meta-Analysis of Paclitaxel-Based Chemotherapy Combined With Traditional Chinese Medicines for Gastric Cancer Treatment
This study aimed to compare the efficacy and safety of traditional Chinese medicines (TCMs) combined with paclitaxel-based chemotherapy and paclitaxel-based chemotherapy alone for gastric cancer treatment. Literature searches (up to September 25, 2019) were performed using the Cochrane Library, EMBASE, PubMed, Chinese Science and Technology Journals (CQVIP), Wanfang, and China Academic Journals (CNKI) databases. Data from 14 randomized controlled trials (RCTs), with 1,109 participants, were included. The results indicated that, compared with paclitaxel-based chemotherapy alone, the combination of TCMs and paclitaxel-based ...
Source: Frontiers in Pharmacology - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

ZnO Quantum Dots Induced Oxidative Stress and Apoptosis in HeLa and HEK-293T Cell Lines
In this study, the cytotoxicity of ZnO QDs was assessed using HeLa cervical cancer cell and HEK-293T human embryonic kidney cell lines. Cell viability was significantly decreased by treatment with 50 µg/ml ZnO QDs after only 6 h, and the cytotoxicity of ZnO QDs was higher in HEK-293T than in HeLa cells. ZnO QDs increased the level of reactive oxygen species and decreased the mitochondria membrane potential in a dose-dependent manner. Several gene expression involved in apoptosis was regulated by ZnO QDs, including bcl-2 gene and caspase. In HeLa cells, ZnO QDs significantly increased early and late apoptosis, but onl...
Source: Frontiers in Pharmacology - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

αvβ3 Integrin Antagonists Enhance Chemotherapy Response in an Orthotopic Pancreatic Cancer Model
This study was undertaken to investigate whether αvβ3 integrin receptor antagonist compounds NDAT and XT199 can suppress the development of cisplatin resistance and cisplatin-induced peripheral neuropathy in an orthotopic pancreatic SUIT2-luc cancer cell mouse model. Anticancer effects of these compounds and their combination with cisplatin were assessed in this tumor mouse model with bioluminescent signaling and histopathology, and a cytokine assay was used to examine expression of inflammatory cytokines IL-1β, IL-6, IL-10, and TNF-α from plasma samples. To determine the neuroprotective effects of th...
Source: Frontiers in Pharmacology - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

Genetic Diversity of HLA Class I and Class II Alleles in Thai Populations: Contribution to Genotype-Guided Therapeutics
Human leukocyte antigen (HLA) class I and II are known to have association with severe cutaneous adverse reactions (SCARs) when exposing to certain drug treatment. Due to genetic differences at population level, drug hypersensitivity reactions are varied, and thus common pharmacogenetics markers for one country might be different from another country, for instance, HLA-A*31:01 is associated with carbamazepine (CBZ)-induced SCARs in European and Japanese while HLA-B*15:02 is associated with CBZ-induced Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) among Taiwanese and Southeast Asian. Such differences p...
Source: Frontiers in Pharmacology - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

Efficacy of Chinese Herbal Formula Sini Zuojin Decoction in Treating Gastroesophageal Reflux Disease: Clinical Evidence and Potential Mechanisms
BackgroundBased on 122 cases reported in China, data mining indicated that Sini Powder (SNP) and the Zuojin Pill (ZJP) are both widely used as the basic recipe for treating Gastroesophageal Reflux Disease (GERD).ObjectivesTo evaluate the intervention effects of Sini Zuojin Decoction (SNZJD) in patients with GERD.MethodsA comprehensive collection of randomized controlled trials (RCTs) using SNZJD in patients with GERD that were published in domestic and foreign journals was made by computer retrieval. RevMan 5.3 software was used for meta-analysis and bias risk assessment, Stata 14.0 software was used for sensitivity analys...
Source: Frontiers in Pharmacology - February 27, 2020 Category: Drugs & Pharmacology Source Type: research

Early-Life Stress Induces Depression-Like Behavior and Synaptic-Plasticity Changes in a Maternal Separation Rat Model: Gender Difference and Metabolomics Study
More than 300 million people suffer from depressive disorders globally. People under early-life stress (ELS) are reportedly vulnerable to depression in their adulthood, and synaptic plasticity can be the molecular mechanism underlying such depression. Herein, we simulated ELS by using a maternal separation (MS) model and evaluated the behavior of Sprague–Dawley (SD) rats in adulthood through behavioral examination, including sucrose preference, forced swimming, and open-field tests. The behavior tests showed that SD rats in the MS group were more susceptible to depression- and anxiety-like behaviors than did the non-...
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

WNT7A Promotes EGF-Induced Migration of Oral Squamous Cell Carcinoma Cells by Activating β-Catenin/MMP9-Mediated Signaling
ConclusionsThe data in this paper indicated that WNT7A could be a potential oncogene in OSCC and identified a novel PI3K/AKT/WNT7A/β-catenin/MMP9 signaling for EGF-induced migration of OSCC cells. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Mechanical Changes and Microfilament Reorganization Involved in Microcystin-LR-Promoted Cell Invasion in DU145 and WPMY Cells
Microcystin-leucine arginine (MC-LR) is a potent tumor initiator that can induce malignant cell transformation. Cellular mechanical characteristics are pivotal parameters that are closely related to cell invasion. The aim of this study is to determine the effect of MC-LR on mechanical parameters, microfilament, and cell invasion in DU145 and WPMY cells. Firstly, 10 μM MC-LR was selected as the appropriate concentration via cell viability assay. Subsequently, after MC-LR treatment, the cellular deformability and viscoelastic parameters were tested using the micropipette aspiration technique. The results showed that MC-LR...
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Iguratimod as a New Drug for Rheumatoid Arthritis: Current Landscape
Iguratimod (IGU) is a novel synthetic small molecule disease modified anti-rheumatic drug approved only in Japan and China up to date. IGU plays an important immunomodulatory role in the synovial tissue of rheumatoid arthritis by inhibiting the production of immunoglobulins and cytokines and regulating T lymphocyte subsets. IGU also regulates bone metabolism by stimulating bone formation while inhibiting osteoclast differentiation, migration, and bone resorption. In clinical trials, IGU was shown to be superior to placebo and not inferior to salazosulfapyridine. Combined therapy of IGU with other disease-modifying anti-rhe...
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Editorial: Alzheimer ’s Disease: Original Mechanisms and Translational Impact
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Exosomes Derived From Epigallocatechin Gallate-Treated Cardiomyocytes Attenuated Acute Myocardial Infarction by Modulating MicroRNA-30a
ConclusionsThe findings showed that EGCG upregulates miR30a, which was efficiently transferred via exosomes between cardiomyocytes, thereby contributing to the suppression of apoptosis and autophagy. By focusing on the cardiomyocyte microenvironment, we identified a new target of EGCG alleviating AMI by regulating apoptosis and autophagy. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Shenfu Injection Promotes Vasodilation by Enhancing eNOS Activity Through the PI3K/Akt Signaling Pathway In Vitro
In conclusion, our study showed the vasodilation effect of SFI in thoracic aorta is mediated entirely by enhancing eNOS activity through the PI3K/Akt signaling pathway, providing novel knowledge on the effect of SFI on shock and HF for future clinical applications. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Synthetic Biology Speeds Up Drug Target Discovery
As a rising emerging field, synthetic biology intends to realize precise regulations of cellular network by constructing artificial synthetic circuits, and it brings great opportunities to treat diseases and discover novel drug targets. Depending on the combination mode of different logic gates, various synthetic circuits are created to carry out multilevel regulations. In given synthetic circuits, drugs often act as inputs to drive circuits operation. It is becoming available to construct drug-responsive gene circuits for experimentally treating various disease models, including metabolic disease, immunity disease, cancer...
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Scutellarin Attenuates the IL-1 β-Induced Inflammation in Mouse Chondrocytes and Prevents Osteoarthritic Progression
Osteoarthritis (OA) is a chronic degenerative disease wherein the articular cartilage exhibits inflammation and degradation. Scutellarin (SCU) is a flavonoid glycoside with a range of pharmacological activities, as shown in previous studies demonstrating its anti-inflammatory activity. How SCU impacts the progression of OA, however, has not been explored to date. Herein, we assessed the impact of SCU on murine chondrocytes in an OA model system. In in vitro assays, we measured chondrocyte expression of key OA-associated factors such as matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombosp...
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Pimavanserin: A Novel Antipsychotic With Potentials to Address an Unmet Need of Older Adults With Dementia-Related Psychosis
Dementia affects more than 40 million people worldwide. When it is accompanied by psychosis, symptom management is especially challenging. Although no drug has been approved by the US Food and Drug Administration (FDA) for psychosis in patients with dementia, atypical antipsychotics are used off-label in severe cases in patients who do not respond to non-pharmacological interventions. However, antipsychotic use in elderly patients with dementia-related psychosis (DRP) is associated with adverse reactions including motor function disorders, cognitive impairment, cerebrovascular events, and increased risk of death. In 2017, ...
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Chemotherapeutic Nanoparticle-Based Liposomes Enhance the Efficiency of Mild Microwave Ablation in Hepatocellular Carcinoma Therapy
In this study, we demonstrated that the uptake of DNPs by HCC cells was increased 1.5-fold compared with that of free DOX. Enhanced synergism was observed in the combination of DNPs and MWA, which induced nearly 80% cell death. The combination of mild MWA and DNPs enhanced the ablation efficiency of HCC with significant inhibition of liver tumors and accounted for the longest survival rate among all groups. A much higher accumulation of the DNPs was observed in the transitional zone than in the ablation zone. No apparent systemic toxicity was observed for any of the treatments after 14 days. The present work demonstrates t...
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Constituents and Metabolites of a French Oak Wood Extract (Robuvit ®) in Serum and Blood Cell Samples of Women Undergoing Hysterectomy
Ellagitannins are signature constituents of oak wood and their consumption has been associated with various health benefits. In vivo, they undergo metabolic degradation including gut microbial metabolism yielding urolithins. Only limited data is available about compounds being present in blood after intake of an extract from French oak wood, Robuvit®. In the course of a randomized, double-blind, controlled clinical investigation, 66 patients undergoing hysterectomy received placebo or 300 mg Robuvit® per day before and over 8 weeks after surgery. Serum and blood cell samples were analyzed by liquid chromatography e...
Source: Frontiers in Pharmacology - February 26, 2020 Category: Drugs & Pharmacology Source Type: research

Relationship Between Ginsenoside Rg3 and Metabolic Syndrome
Metabolic syndrome is an important public health issue and is associated with a more affluent lifestyle. Many studies of metabolic syndrome have been reported, but its pathogenesis remains unclear and there is no effective treatment. The ability of natural compounds to ameliorate metabolic syndrome is currently under investigation. Unlike synthetic chemicals, such natural products have proven utility in various fields. Recently, ginsenoside extracted from ginseng and ginseng root are representative examples. For example, ginseng is used in dietary supplements and cosmetics. In addition, various studies have reported the ef...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Dexmedetomidine Protects Against Lipopolysaccharide-Induced Acute Kidney Injury by Enhancing Autophagy Through Inhibition of the PI3K/AKT/mTOR Pathway
ConclusionsHere, we demonstrate a novel mechanism in which DEX protects against LPS-induced AKI. DEX enhances autophagy, which results in the removal of damaged mitochondria and reduces oxidative stress and apoptosis in LPS-induced AKI through the α2-AR and inhibition of the PI3K/AKT/mTOR pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway
In this study, we investigated the anti-metastatic potential of this compound on highly metastatic murine B16-F10 and human A375 melanoma cells. We found that TAP7f inhibited cell adhesion, migration and invasion in a dose-dependent manner. Additionally, we demonstrated that TAP7f downregulated integrin αvβ3 expression and Wnt/β-catenin pathway, a signaling cascade commonly related to tumor invasion and metastasis. Thus, TAP7f reduced both the enzymatic activity and the expression levels of matrix-metalloproteinases-2 and -9 in a time dependent manner. Moreover, TAP7f inhibited the expression of the transcr...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Effect of Transcranial Direct Current Stimulation Combined With Patient-Controlled Intravenous Morphine Analgesia on Analgesic Use and Post-Thoracotomy Pain. A Prospective, Randomized, Double-Blind, Sham-Controlled, Proof-of-Concept Clinical Trial
ConclusionIn lung cancer patients undergoing thoracotomy, three to five tDCS sessions significantly reduced cumulative postoperative morphine use, maximum VAS pain scores with cough, and pain interference with cough on postoperative day 5, but there was no obvious long-term benefit from tDCS. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Pathogenesis of Chronic Plaque Psoriasis and Its Intersection With Cardio-Metabolic Comorbidities
Psoriasis is a chronic, systemic immune-mediated disease characterized by development of erythematous, indurated, scaly, pruritic plaques on the skin. Psoriasis is frequently associated to comorbidities, including psoriatic arthritis, cardiovascular diseases, diabetes mellitus, obesity, non-alcoholic fatty liver disease, and inflammatory bowel diseases. In this review, we discuss the pathophysiological relationship between psoriasis and cardio-metabolic comorbidities and the importance of therapeutic strategies to reduce systemic inflammation in patients with moderate-to-severe psoriasis. Pathogenesis of psoriasis and its ...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Escins Isolated from Aesculus chinensis Bge. Promote the Autophagic Degradation of Mutant Huntingtin and Inhibit its Induced Apoptosis in HT22 cells
In conclusion, we are the first to report that the escins, including EA, EB and IEA are novel autophagy inducers that degrade mHtt and inhibit mHtt-induced apoptosis in vitro and in vivo. As a result of these findings, the triterpenoid saponins in ACB might be considered to be promising candidates for the treatment of HD in the future. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Eriodictyol Inhibits Proliferation, Metastasis and Induces Apoptosis of Glioma Cells via PI3K/Akt/NF- κB Signaling Pathway
In this study, we found that eriodictyol has anti-tumor activity in lung, colon, breast, pancreas, and liver cancer, and most significantly in glioma cell lines. Eriodictyol dose- and time-dependently suppresses cell proliferation, migration, and invasion in U87MG and CHG-5 glioma cells. In addition, eriodictyol induces apoptosis in U87MG and CHG-5 cells, as evaluated by flow cytometry, immunofluorescence, and Western blot. Furthermore, eriodictyol downregulates the phosphoinositide 3-kinase (PI3K)/Akt/NF-κB signaling pathway in a concentration-dependent manner. Moreover, the effects of eriodictyol on the apoptosis o...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Structure –Function Studies and Mechanism of Action of Snake Venom L-Amino Acid Oxidases
Snake venom L-amino acid oxidases (SV-LAAOs) are the least studied venom enzymes. These enzymes catalyze the stereospecific oxidation of an L-amino acid to their corresponding α-keto acid with the liberation of hydrogen peroxide (H2O2) and ammonia (NH3). They display various pathological and physiological activities including induction of apoptosis, edema, platelet aggregation/inhibition, hemorrhagic, and anticoagulant activities. They also show antibacterial, antiviral and leishmanicidal activity and have been used as therapeutic agents in some disease conditions like cancer and anti-HIV drugs. Although the crystal ...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Ferulic Acid Attenuates Hypoxia/Reoxygenation Injury by Suppressing Mitophagy Through the PINK1/Parkin Signaling Pathway in H9c2 Cells
Ferulic acid protects against cardiac injury by scavenging free radicals. However, the role of mitophagy in ferulic acid-induced cardioprotection remains obscure. In the present study, H9c2 cells were exposed to hypoxia/reoxygenation and ferulic acid treatment during hypoxia. We illustrated the impact of ferulic acid on oxidative damage in H9c2 cells. Our results showed that ferulic acid significantly attenuated apoptosis induced by hypoxia/reoxygenation injury and reduced mitochondrial dysfunction, evidenced by a decline in the overproduction of reactive oxygen species and ATP depletion and recovery of the membrane potent...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Treatment With 2-Pentadecyl-2-Oxazoline Restores Mild Traumatic Brain Injury-Induced Sensorial and Neuropsychiatric Dysfunctions
Traumatic brain injury (TBI) represents an important public health problem and is followed by neuroinflammation and neurological dysfunctions. It has been suggested that brain trauma is often associated to deep behavioral alterations and chronic pain-like syndrome. Despite inducing minimal brain damage, mild TBI (mTBI) leads to persistent behavioral changes, including anxiety, depression, social interaction impairment, and aggressiveness. The clinical management of these symptoms is still unsatisfactory and new pharmacological treatments are needed, especially for the aggressiveness and depression. In a mouse model of mTBI...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Divergence and Convergence of Cerebral Ischemia Pathways Profile Deciphers Differential Pure Additive and Synergistic Mechanisms
ConclusionThe divergence pathways of pure additive effect of BJ were mainly related to cell adhesion and G-protein signaling, while the pure synergistic mechanism of JU depended on metabolism, translation and DNA damage. Such a systematic analysis of pathways may provide an important paradigm to reveal the pharmacological mechanisms underlying drug combinations. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Calcium Handling Defects and Cardiac Arrhythmia Syndromes
Calcium ions (Ca2+) play a major role in the cardiac excitation-contraction coupling. Intracellular Ca2+ concentration increases during systole and falls in diastole thereby determining cardiac contraction and relaxation. Normal cardiac function also requires perfect organization of the ion currents at the cellular level to drive action potentials and to maintain action potential propagation and electrical homogeneity at the tissue level. Any imbalance in Ca2+ homeostasis of a cardiac myocyte can lead to electrical disturbances. This review aims to discuss cardiac physiology and pathophysiology from the elementary membrane...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Predicting or Pretending: Artificial Intelligence for Protein-Ligand Interactions Lack of Sufficiently Large and Unbiased Datasets
We examined the model performance of atomic convolutional neural network (ACNN) on the PDBbind core set and achieved a Pearson R2 of 0.73 between experimental and predicted binding affinities. Strikingly, the ACNN models did not require learning the essential protein-ligand interactions in complex structures and achieved similar performance even on datasets containing only ligand structures or only protein structures, while data splitting based on similarity clustering (protein sequence or ligand scaffold) significantly reduced the model performance. We also identified the property and topology biases in the DUD-E dataset ...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects
This review aims to present completed clinical trial data surrounding the medicinal benefits and potential side effects of the increasingly popular cannabidiol (CBD)-based drug products, specifically Epidiolex. The article is divided into two sections based on if the ailment being treated by this cannabinoid is classified as either physiological or neurological conditions. In addition to describing the current status, we also examined the different primary and secondary outcomes recorded for each study, which varies greatly depending on the funding source of the clinical trial. With the recent FDA-approval of Epidiolex, th...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

The Specialist in Medicines Development (SMD) as a Vocational Program in Pharmaceutical Medicine: The Japanese and Italian Experience
The growing complexity of the drug development process requires globally recognized professionals who have not only completed the cognitive path of competence, i.e. the specialized post graduate course in Pharmaceutical Medicine, but suggests that these individuals should join a vocational training program in order to consolidate the seven competencies which characterize a competent Pharmaceutical Professional. The Specialist in Medicines Development (SMD) program developed by the IMI project PharmaTrain and further supported by the IMI project IMI-TRAIN can be considered a prototype vocational program. In order to test th...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Significance of Ligand-Anchored Polymers for Drug Targeting in the Treatment of Colonic Disorders
Treatment of a variety of bowel diseases like Crohn’s disease, ulcerative colitis, colonic cancers, colonic pathologies, and systemic delivery of drugs at the target sites can be done with the help of targeted drug delivery technique. Conventional colon specific drug delivery systems lack specificity and release significant amount of drug prior reaching the target site. Hence, efficient drug delivery system that ensures effective release of the drug at the colon is still a sought after research arena. Ligand anchored therapy is a strong and effective approach to execute drug delivery in selective target cells, for bo...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Metabolic Profiling Reveals an Abnormal Pattern of Serum Fatty Acids in MRL/lpr Mice Under Treatment With Prednisone
Glucocorticoids (GCs) are commonly used to treat systemic lupus erythematosus (SLE). Unfortunately, excessive GCs can induce many side effects associated with disordered fatty acid (FA) metabolism. Although an increased level of total FA has been found after GCs treatment, it is not clear whether all FA species increased or only certain FA species were altered. A gas chromatography–mass spectrometry-based FA profiling approach was performed to reveal the alterations of FA species in SLE model mice (MRL/lpr) after treatment with 5 mg/kg of prednisone. The study showed a distinct FA profile in MRL/lpr mice compared to ...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Progress in Research on the Role of FGF in the Formation and Treatment of Corneal Neovascularization
Corneal neovascularization (CNV) is a sight-threatening disease usually associated with inflammatory, infectious, degenerative, and traumatic disorders of the ocular surface. Fibroblast growth factor (FGF) family members play an important role in angiogenesis to induce corneal neovascularization, which significantly affects the differentiation, proliferation, metastasis, and chemotaxis of vascular endothelial cells. Both acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) demonstrate positive staining in capillaries and induce corneal stromal cells. The anabolism of endothelial cells is induced...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Bungeanum Improves Cognitive Dysfunction and Neurological Deficits in D-Galactose-Induced Aging Mice via Activating PI3K/Akt/Nrf2 Signaling Pathway
Zanthoxylum bungeanum Maxim (Rutaceae), a popular condiment and dietetic herbal medicine, has been used traditionally in the treatment of forgetfulness, as recorded in Shen Nong's Herbal Medicine, an old Chinese medicine book. To explore effects and potential mechanisms of it, extracts of Z. bungeanum through water (WEZ), volatile oil (VOZ), petroleum ether (PEZ), and methylene chloride (MCZ) were used to treat the memory loss induced in D-galactose-induced aging mice. The impaired memory was significantly alleviated after WEZ and VOZ extract treatment. WEZ and VOZ extracts also prevented D-galactose-induced hippocampal ne...
Source: Frontiers in Pharmacology - February 25, 2020 Category: Drugs & Pharmacology Source Type: research

Corrigendum: Improvement of Sepsis Prognosis by Ulinastatin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - February 21, 2020 Category: Drugs & Pharmacology Source Type: research

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