Advances in Drug Delivery via Biodegradable Ureteral Stent for the Treatment of Upper Tract Urothelial Carcinoma
Drug eluting ureteral stent is an effective means for local drug delivery to the urinary tract. It can potentially solve a variety of upper urinary tract problems, such as stent-related urinary tract infections and discomfort, ureteral stricture, and neoplastic diseases. However, the release of drug elutes on the surface of biostable stents is unsustainable and uncontrollable. With the development of biomaterial science, the emergence of biodegradable ureteral stents (BUSs) provides a new approach for local drug delivery in the urinary tract. The drugs can be continuously released in a controlled manner from a drug-eluting...
Source: Frontiers in Pharmacology - March 17, 2020 Category: Drugs & Pharmacology Source Type: research

Biocompatible Nutmeg Oil-Loaded Nanoemulsion as Phyto-Repellent
Plant essential oils are widely used in perfumes and insect repellent products. However, due to the high volatility of the constituents in essential oils, their efficacy as a repellent product is less effective than that of synthetic compounds. Using a nanoemulsion as a carrier is one way to overcome this disadvantage of essential oils. Nutmeg oil-loaded nanoemulsion (NT) was prepared using a high speed homogenizer and sonicator with varying amounts of surfactant, glycerol, and distilled water. Using a phase diagram, different formulations were tested for their droplet size and insect repellent activity. The nanoemulsion c...
Source: Frontiers in Pharmacology - March 17, 2020 Category: Drugs & Pharmacology Source Type: research

Nintedanib Inhibits Wnt3a-Induced Myofibroblast Activation by Suppressing the Src/ β-Catenin Pathway
In this study, we found that nintedanib attenuated myofibroblast activation through inhibiting the expression of genes downstream of Wnt signaling such as Cyclin D1, Wisp1, and S100a4. Further experiments showed that nintedanib inhibited Wnt3a-induced β-catenin nuclear translocation through suppressing Src kinase activation and β-catenin Y654 phosphorylation. Additionally, Src knockdown fibroblasts exhibited a phenotype similar to that of the nintedanib treatment group, and the inhibitory effects of nintedanib were consistent with those of the Src kinase inhibitor KX2-391. In summary, our study shows that ninteda...
Source: Frontiers in Pharmacology - March 16, 2020 Category: Drugs & Pharmacology Source Type: research

Modulation of Pain Sensitivity by Chronic Consumption of Highly Palatable Food Followed by Abstinence: Emerging Role of Fatty Acid Amide Hydrolase
In this study, we investigated whether long-term exposure to a CAF diet could modify pain sensitivity and explored the role of the cannabinergic system in this modification. Male Sprague–Dawley rats were divided into two groups: one fed with standard chow only (CO) and the other with extended access (EA) to a CAF diet. Hot plate and tail flick tests were used to evaluate pain sensitivity. At the end of a 40-day CAF exposure, EA rats showed a significant increase in the pain threshold compared to CO rats, finding probably due to up-regulation of CB1 and mu-opioid receptors. Instead, during abstinence from palatable fo...
Source: Frontiers in Pharmacology - March 16, 2020 Category: Drugs & Pharmacology Source Type: research

Antiproliferative Effects of Roylea cinerea (D. Don) Baillon Leaves in Immortalized L6 Rat Skeletal Muscle Cell Line: Role of Reactive Oxygen Species Mediated Pathway
Roylea cinerea (D. Don) Baill. (Lamiaceae) is an indigenous plant of Western Himalayas, and has been used by the native population for the treatment of various diseases such as fever, malaria, diabetes, jaundice, and skin ailments. However, limited proportion of pharmacological and toxicological information is available on the bioactive properties of this plant. Therefore, the present study was designed to explore the anti-oxidant and anti-proliferative activities of Roylea cinerea. Methanolic extracts of leaves and stem of Roylea cinerea were prepared through maceration procedure and evaluated for the antioxidant activity...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

The Apelin/APJ System in Psychosis and Neuropathy
Apelin, an endogenous neuropeptide, has been identified as the cognate ligand for the G-protein-coupled receptor APJ. Apelin, APJ messenger RNA, and protein are widely expressed in the central nervous system and peripheral tissues of humans and animals. The apelin/APJ system has been implicated in diverse physiological and pathological processes. The present article reviews the progress of the latest research investigating the apelin/APJ system in pain, depression, anxiety, memory, epilepsy, neuroprotection, stroke, and brain injury and protection, and highlights its promising potential as a therapeutic target for treatmen...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Preparation and Characterization of Chitosan Nanoparticles for Chemotherapy of Melanoma Through Enhancing Tumor Penetration
In this study, positively charged nanoparticles based on chitosan were developed and synthesized to enhance tumor penetration capability of 10-Hydroxycamptothecin (HCPT) in order to improve the chemotherapeutic effect of melanoma. The HCPT encapsulated nanoparticles were noted as NPs/HCPT. NPs/HCPT was characterized by dynamic light scattering and zeta potential measurements. In addition, cell uptake, in vitro cytotoxicity, apoptosis and in vivo antitumor activity of NPs/HCPT were further investigated. The average diameter of NPs/HCPT was approximately 114.6 ± 4.1 nm. The viability of murine melanoma cell lines (B16...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Pathways Connecting Late-Life Depression and Dementia
In conclusion, different potential pathophysiological links between dementia and depression highlight several specific synergistic and multifaceted treatment possibilities, depending on the individual risk profile of the patient. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

(-)-Sativan Inhibits Tumor Development and Regulates miR-200c/PD-L1 in Triple Negative Breast Cancer Cells
In this study, SA displayed a significant inhibitory effect on the proliferation of TNBC cells by inducing apoptosis. SA increased Bax expression, and decreased Bcl-2 protein levels. SA inhibited cell migration and invasion of MDA-MB-231 and BT-549 cells. SA could decrease N-cadherin, Snail, Vimentin, and PD-L1 expression. SA increased miR-200c expression, and decreased PD-L1 expression. Luciferase assay showed that miR-200c directly targeted PD-L1. SA promoted tumor cell susceptibility to CTL-mediated lysis. Further study confirmed that SA could inhibit PD-L1 expression and EMT by up-regulating miR-200c. In vivo results d...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Effect of Berberine on Atherosclerosis and Gut Microbiota Modulation and Their Correlation in High-Fat Diet-Fed ApoE −/− Mice
Atherosclerosis and its associated cardiovascular diseases (CVDs) are serious threats to human health and have been reported to be associated with the gut microbiota. Recently, the role of berberine (BBR) in atherosclerosis and gut microbiota has begun to be appreciated. The purposes of this study were to observe the effects of high or low doses of BBR on atherosclerosis and gut microbiota modulation, and to explore their correlation in ApoE–/– mice fed a high-fat diet. A significant decrease in atherosclerotic lesions was observed after treatment with BBR, with the effect of the high dose being more obvious. B...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Striatal Dopamine D2-Muscarinic Acetylcholine M1 Receptor –Receptor Interaction in a Model of Movement Disorders
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor control deficits, which is associated with the loss of striatal dopaminergic neurons from the substantia nigra. In parallel to dopaminergic denervation, there is an increase of acetylcholine within the striatum, resulting in a striatal dopaminergic–cholinergic neurotransmission imbalance. Currently, available PD pharmacotherapy (e.g., prodopaminergic drugs) does not reinstate the altered dopaminergic–cholinergic balance. In addition, it can eventually elicit cholinergic-related adverse effects. Here, we investigated the interp...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Pathophysiological Mechanisms and Potential Therapeutic Targets in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), is a hereditary small-vessels angiopathy caused by mutations in the NOTCH 3 gene, located on chromosome 19, usually affecting middle-ages adults, whose clinical manifestations include migraine with aura, recurrent strokes, mood disorders, and cognitive impairment leading to dementia and disability. In this review, we provide an overview of the current knowledge on the pathogenic mechanisms underlying the disease, focus on the corresponding therapeutic targets, and discuss the most promising treatment strategies currently u...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Time- and Race-Specific Haematological Reference Intervals for Healthy Volunteer Trials: A Retrospective Analysis of Pooled Data From Multiple Phase I Trials
This study pools data from multiple phase I trials, assesses the effects of race and time of day on WBC count, and compares it to the existing literature to establish race and time-specific RIs. A total 13,332 venous blood samples obtained from 7,157 healthy male and female volunteers at the time of screening or admission (predosing) who took part in 35 phase I trials over a period of seven years were pooled and the data were analyzed using generalised estimating equation models. Adjusted RI of total WBC count and its individual parameters were then calculated according to time of day (morning vs. evening) for both black a...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Hazards of Using Masking Protocols When Performing Ligand Binding Assays: Lessons From the Sigma-1 and Sigma-2 Receptors
Sigma-1 and sigma-2 receptors are emerging therapeutic targets. Although the molecular identity of the sigma-2 receptor has recently been determined, receptor quantitation has used, and continues to use, the sigma-1 selective agents (+) pentazocine or dextrallorphan to mask the sigma-1 receptor in radioligand binding assays. Here, we have assessed the suitability of currently established saturation and competition binding isotherm assays that are used to quantify parameters of the sigma-2 receptor. We show that whilst the sigma-1 receptor mask (+) pentazocine has low affinity for the sigma-2 receptor (Ki 406 nM), it can ef...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Knowledge Mapping of Angelica sinensis (Oliv.) Diels (Danggui) Research: A Scientometric Study
ConclusionThe present scientometric study provides an overview of the development of AS research over the previous decade using quantitative and qualitative methods, and this overview can provide references for researchers focusing on AS. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Regulation of the Ras-Related Signaling Pathway by Small Molecules Containing an Indole Core Scaffold: A Potential Antitumor Therapy
The Ras-Related signaling pathway plays an important role in cell development and differentiation. A growing body of evidence collected in recent years has shown that the aberrant activation of Ras is associated with tumor-related processes. Several studies have indicated that indole and its derivatives can target regulatory factors and interfere with or even block the aberrant Ras-Related pathway to treat or improve malignant tumors. In this review, we summarize the roles of indole and its derivatives in the isoprenylcysteine carboxyl methyltransferase-participant Ras membrane localization signaling pathway and Ras-GTP/Ra...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Rosiglitazone Protects Endothelial Cells From Irradiation-Induced Mitochondrial Dysfunction
ConclusionPre-existing mitochondrial damage sensitizes endothelial cells to ionizing radiation-induced mitochondrial dysfunction. Rosiglitazone protects endothelial cells from the detrimental effects of radiation exposure on mitochondrial metabolism and oxidative stress. Thus, our findings indicate that rosiglitazone may have potential value as prophylactic for radiation-induced atherosclerosis. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Fitter Mitochondria Are Associated With Radioresistance in Human Head and Neck SQD9 Cancer Cells
The clinical management of head and neck squamous cell carcinoma (HNSCC) commonly involves chemoradiotherapy, but recurrences often occur that are associated with radioresistance. Using human SQD9 laryngeal squamous cell carcinoma cancer cells as a model, we aimed to identify metabolic changes associated with acquired radioresistance. In a top-down approach, matched radiosensitive and radioresistant SQD9 cells were generated and metabolically compared, focusing on glycolysis, oxidative phosphorylation (OXPHOS) and ROS production. The cell cycle, clonogenicity, tumor growth in mice and DNA damage-repair were assessed. Mitoc...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction
Although often overlooked in our daily lives, saliva performs a host of necessary physiological functions, including lubricating and protecting the oral cavity, facilitating taste sensation and digestion and maintaining tooth enamel. Therefore, salivary gland dysfunction and hyposalivation, often resulting from pathogenesis of the autoimmune disease Sjögren’s syndrome or from radiotherapy of the head and neck region during cancer treatment, severely reduce the quality of life of afflicted patients and can lead to dental caries, periodontitis, digestive disorders, loss of taste and difficulty speaking. Since thei...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Proteomics-Based Characterization of miR-574-5p Decoy to CUGBP1 Suggests Specificity for mPGES-1 Regulation in Human Lung Cancer Cells
MicroRNAs (miRs) are one of the most important post-transcriptional repressors of gene expression. However, miR-574-5p has recently been shown to positively regulate the expression of microsomal prostaglandin E-synthase-1 (mPGES-1), a key enzyme in the prostaglandin E2 (PGE2) biosynthesis, by acting as decoy to the RNA-binding protein CUG-RNA binding protein 1 (CUGBP1) in human lung cancer. miR-574-5p exhibits oncogenic properties and promotes lung tumor growth in vivo via induction of mPGES-1-derived PGE2 synthesis. In a mass spectrometry-based proteomics study, we now attempted to characterize this decoy mechanism in A54...
Source: Frontiers in Pharmacology - March 13, 2020 Category: Drugs & Pharmacology Source Type: research

Model-Based Biomarker Selection for Dose Individualization of Tyrosine-Kinase Inhibitors
This study investigated the efficacy, safety, and economical aspects of alternative dosing options for sunitinib in gastro-intestinal stromal tumors (GIST) and axitinib in metastatic renal cell carcinoma (mRCC). Dose individualization based on drug concentration, adverse effects, and sVEGFR-3 was explored using a modeling framework connecting pharmacokinetic and pharmacodynamic models, as well as overall survival. Model-based simulations were performed to investigate four different scenarios: (I) the predicted value of high-dose pulsatile schedules to improve clinical outcomes as compared to regular daily dosing, (II) the ...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Intravitreal Anti-VEGF Drugs and Signals of Dementia and Parkinson-Like Events: Analysis of the VigiBase Database of Spontaneous Reports
ConclusionPresent findings suggest a potential signal for Parkinson’s disease related to intravitreal ranibizumab. This is supported by several biologically plausible mechanisms but requires confirmation through pharmacoepidemiological studies, especially because of the low number of cases. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Novel Anti-Interleukin-1 β Therapy Preserves Retinal Integrity: A Longitudinal Investigation Using OCT Imaging and Automated Retinal Segmentation in Small Rodents
Retinopathy of prematurity (ROP) is the leading cause of blindness in neonates. Inflammation, in particular interleukin-1β (IL-1β), is increased in early stages of the disorder, and contributes to inner and outer retinal vasoobliteration in the oxygen-induced retinopathy (OIR) model of ROP. A small peptide antagonist of IL-1 receptor, composed of the amino acid sequence, rytvela, has been shown to exert beneficial anti-inflammatory effects without compromising immunovigilance-related NF-κB in reproductive tissues. We conducted a longitudinal study to determine the efficacy of “rytvela” in preser...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Silibinin Induces G2/M Cell Cycle Arrest by Activating Drp1-Dependent Mitochondrial Fission in Cervical Cancer
In conclusion, we are the first to demonstrate that SB induces cervical cancer cell G2/M cell cycle arrest by activating Drp1-dependent mitochondrial fission dysfunction. This study suggests the strategy of inducing Drp1-dependent mitochondrial fission for cervical cancer prevention and treatment. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Inhaled Phosphodiesterase 4 (PDE4) Inhibitors for Inflammatory Respiratory Diseases
PDE4 inhibitors can suppress a variety of inflammatory cell functions that contribute to their anti-inflammatory actions in respiratory diseases like chronic obstructive pulmonary disease (COPD) and asthma. The systemically delivered PDE4 inhibitor roflumilast has been approved for use in a subset of patients with severe COPD with chronic bronchitis and a history of exacerbations. Use of systemically delivered PDE4 inhibitors has been limited by systemic side effects. Inhaled PDE4 inhibitors have been considered as a viable alternative to increase tolerability and determine the maximum therapeutic potential of PDE4 inhibit...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Asking More of Our EHR Systems to Improve Outcomes for Pediatric Patients
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Dendrobium officinale Polysaccharide Protected CCl4-Induced Liver Fibrosis Through Intestinal Homeostasis and the LPS-TLR4-NF- κB Signaling Pathway
We explored the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on CCl4-induced liver fibrosis with respect to the intestinal hepatic axis using a rat model. Histopathological staining results showed that DOP alleviated extensive fibrous tissue proliferation in interstitium and lessened intestinal mucosal damage. Western blot and PCR results showed that DOP maintained intestinal balance by upregulating the expression of tight junction proteins such as occludin, claudin-1, ZO-1, and Bcl-2 proteins while downregulating the expression of Bax and caspase-3 proteins in the intestine. The transepithelial electr...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

A Novel Sulfonyl-Based Small Molecule Exhibiting Anti-cancer Properties
Phenotypic screening is an ideal strategy for the discovery of novel bioactive molecules. Using a customized high-throughput screening (HTS) assay employing primary T lymphocytes, we screened a small library of 4,398 compounds with unknown biological function/target to identify compounds eliciting immunomodulatory properties and discovered a sulfonyl-containing hit, we named InhiTinib. This compound inhibited interferon (IFN)-gamma production and proliferation of primary CD3+ T cells without inducing cell death. In contrast, InhiTinib triggered apoptosis in several murine and human cancer cell lines. Besides, the compound ...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation
In this study, we evaluated the potential of very early intervention with the active form of vitamin D (1,25-dihydroxyvitamin D3) to control neuroinflammation during EAE development. EAE was induced in C57BL/6J mice and 1,25-dihydroxyvitamin D3 administration began 1 day after disease induction. This procedure decreased prevalence, clinical score, inflammation, and demyelination. It also reduced MHCII expression in macrophages and microglia as well as the level of oxidative stress and messenger RNA (mRNA) expression for NLRP3, caspase-1, interleukin (IL)-1β, CX3CR1, CCL17, RORc and Tbx21 at the CNS. Otherwise, mRNA ex...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Medicinal Plants and Phytochemicals for the Treatment of Pulmonary Hypertension
ConclusionStudies have shown that herbs and phytochemicals used to treat PH do their effects from six mechanisms. These mechanisms include antiproliferative, antioxidant, antivascular remodeling, anti-inflammatory, vasodilatory and apoptosis inducing actions. According to the present study, many of these medicinal plants and phytochemicals can have effects that are more therapeutic than chemical drugs if used appropriately. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Hypertension Is Associated With Intestinal Microbiota Dysbiosis and Inflammation in a Brazilian Population
Hypertension is a major global health challenge, as it represents the main risk factor for stroke and cardiovascular disease. It is a multifactorial clinical condition characterized by high and sustained levels of blood pressure, likely resulting from a complex interplay of endogenous and environmental factors. The gut microbiota has been strongly supposed to be involved but its role in hypertension is still poorly understood. In an attempt to fill this gap, here we characterized the microbial composition of fecal samples from 48 hypertensive and 32 normotensive Brazilian individuals by next-generation sequencing of the 16...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members
Autophagy is a cellular degradative process that has multiple important actions in cancer. Autophagy modulation is under consideration as a promising new approach to cancer therapy. However, complete autophagy dysregulation is likely to have substantial undesirable side effects. Thus, more targeted approaches to autophagy modulation may prove clinically beneficial. One potential avenue to achieving this goal is to focus on the actions of tripartite motif-containing protein family members (TRIMs). TRIMs have key roles in an array of cellular processes, and their dysregulation has been extensively linked to cancer risk and p...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Synergistic Effects of Erzhi Pill Combined With Methotrexate on Osteoblasts Mediated via the Wnt1/LRP5/ β-Catenin Signaling Pathway in Collagen-Induced Arthritis Rats
This study demonstrated that EZP in combination with MTX played a synergistic role in regulating OBs in RA, which was connected to the modulatory effect of EZP and MTX on the Wnt1/LRP5/β-catenin signaling pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Herbal Therapy for the Treatment of Acetaminophen-Associated Liver Injury: Recent Advances and Future Perspectives
Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury worldwide, and mitochondrial oxidative stress is considered the major event responsible for APAP-associated liver injury (ALI). Despite the identification of N-acetyl cysteine, a reactive oxygen species scavenger that is regarded as an effective clinical treatment, therapeutic effectiveness remains limited due to rapid disease progression and diagnosis at a late phase, which leads to the need to explore various therapeutic approaches. Since the early 1990s, a number of natural products and herbs have been found to have hepatoprotective effects ...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Editorial: The Canonical and Non-Canonical Endocannabinoid System as a Target in Cancer and Acute and Chronic Pain
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Astaxanthin Ameliorated Parvalbumin-Positive Neuron Deficits and Alzheimer ’s Disease-Related Pathological Progression in the Hippocampus of AppNL-G-F/NL-G-F Mice
Growing evidence suggests that oxidative stress due to amyloid β (Aβ) accumulation is involved in Alzheimer’s disease (AD) through the formation of amyloid plaque, which leads to hyperphosphorylation of tau, microglial activation, and cognitive deficits. The dysfunction or phenotypic loss of parvalbumin (PV)-positive neurons has been implicated in cognitive deficits. Astaxanthin is one of carotenoids and known as a highly potent antioxidant. We hypothesized that astaxanthin’s antioxidant effects may prevent the onset of cognitive deficits in AD by preventing AD pathological processes associated with o...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Neuroprotective Effect of Danhong Injection on Cerebral Ischemia-Reperfusion Injury in Rats by Activation of the PI3K-Akt Pathway
In this study, we investigated the neuroprotective effect of DHI against cerebral ischemia-reperfusion injury mediated via the PI3K-Akt signaling pathway. After establishing the model of middle cerebral artery occlusion (MCAO), 60 male Sprague–Dawley rats were allocated to six groups as follows: sham, MCAO, DHI (MCAO + DHI), LY294002 (MCAO + LY294002 [PI3K-Akt pathway specific inhibitor]), DHI + LY294002 (MCAO + DHI + LY294002), and NMDP + LY294002 (MCAO + NMDP [nimodipine] + LY294002). Hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to evaluate t...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Chronic Fluoxetine Impairs the Effects of 5-HT1A and 5-HT2C Receptors Activation in the PAG and Amygdala on Antinociception Induced by Aversive Situation in Mice
Growing evidence suggests an important role of fluoxetine with serotonin 5-HT1A and 5-HT2C receptors in the modulation of emotion and nociception in brain areas such as the amygdala and periaqueductal gray (PAG). Acute fluoxetine impairs 5-HT2C (but not 5-HT1A) receptor activation in the amygdaloid complex. Given that fluoxetine produces its clinical therapeutic effects only when given chronically, this study investigated the effects of chronic treatment with fluoxetine on the effects produced by 5-HT1A or 5-HT2C receptors activation in the amygdala or PAG on fear-induced antinociception. We recorded the effects of chronic...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Repurposing Clinical Drugs as AdoMetDC Inhibitors Using the SCAR Strategy
With the escalating costs in drug development, discovering new uses of approved drugs, i.e., drug repurposing, has attracted increasing interest. Spermidine and spermine are important polyamines for most cells and their biosynthesis are strictly regulated by the polyamine metabolic network. In cancerous cells and tumor environments, the concentrations of polyamines are much higher than in normal cells. During the synthesis of spermidine and spermine, an amino-propyl group is provided by decarboxylated S-adenosylmethionine, and the latter is generated from S-adenosylmethionine by AdoMetDC (AdoMet decarboxylase). Therefore, ...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

The Reliability of Histamine Pharmacodynamic Response Phenotype Classification in Children With Allergic Disease
We have identified distinct histamine pharmacodynamic response phenotypes in children with allergic disease utilizing histamine iontophoresis with laser Doppler (HILD). These response phenotypes may be relevant in guiding therapeutic decision making for agents targeting the allergic response pathways. However, the reliability of these response phenotypes has not been assessed. Therefore, we performed HILD in children with allergic rhinitis and/or asthma on two to three separate occasions. HILD response-time data were analyzed in NONMEM using a linked effect PKPD model. Examination of observed vs. classified response phenot...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Erratum: Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A
In conclusion, miR-18a-5p may be a useful drug target for pathologic ocular neovascularization. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Ancient Chinese Medicine Herbal Formula Huanglian Jiedu Decoction as a Neoadjuvant Treatment of Chemotherapy by Improving Diarrhea and Tumor Response
Conclusion: Our study suggests the potential of HLJDD as a neoadjuvant treatment of chemotherapy by reducing diarrhea and improving tumor response. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

The Role of Fibroblast Growth Factor 10 Signaling in Duodenal Atresia
ConclusionDetermining the etiology of DA in humans is a clinical and scientific imperative. Fgf10/Fgfr2b murine models represent current science’s best key to unlocking this mystery. However, further research is required to understand the complex role of FGF10/FGFR2b signaling in DA development. Such complexity is expected, given the lethality of their associated defects makes ubiquitous interruption of either Fgf10 or Fgfr2b genes an unlikely cause of DA in humans. Rather, local or tissue-specific mutation in Fgf10, Fgfr2b, or their downstream targets, is the hypothesized basis of DA etiology. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

In silico Docking Studies of Fingolimod and S1P1 Agonists
We examined the binding properties of the endogenous substrate as well as a selection of synthetic sphingosine-derived S1P1 modulators of S1P1 with in silico docking simulations using the software package Molecular Operating Environment® (MOE®). The modeling studies reveal the relevance of phosphorylation, i.e., the presence of a phosphate or phosphonate moiety within the substrate for successful binding to occur, and indicate which residues are responsible for S1P1 binding of the most prominent sphingosine-1-phosphate receptor (S1PR) modulators, including fingolimod and its structural relatives. Furthermore, trend...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

SIRT1 Mediates Effects of FGF21 to Ameliorate Cisplatin-Induced Acute Kidney Injury
In this study, we show that the expression of FGF21 is significantly upregulated in both in vitro and in vivo cisplatin-induced AKI models. Administration of recombinant FGF21 to cisplatin-induced AKI mice resulted in significantly decreased blood urea nitrogen (BUN) and serum creatinine levels, as well as significantly reduced protein levels of kidney injury molecule-1 (TIM-1), C-caspase 3, and Bax. H&E-stained kidney sections from cisplatin-induced AKI mice treated with recombinant FGF21 showed a relatively normal renal tissue structure, a reduced number of necrotic sites and vacuolar changes, and decreased casts, su...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Fumitremorgin C Attenuates Osteoclast Formation and Function via Suppressing RANKL-Induced Signaling Pathways
In this study, we aim to find out whether Fum can inhibit the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and function. The results showed that Fum could significantly attenuate osteoclast formation and function at concentrations from 2.5 to 10 µM. The protein expression of bone resorption factors such as NFATc1, cathepsin K, V-ATPase-d2, and c-Fos was suppressed with the treatment of Fum at a concentration of 10 µM. In addition, Fum was also shown to suppress the activity of NF-κB, intracellular reactive oxygen species level, and MAPK pathway. Taken together,...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Targeting Neuroinflammation in Neovascular Retinal Diseases
Retinal blood vessels provide the necessary energy, nutrients and oxygen in order to support visual function and remove harmful particles from blood, thus acting to protect neuronal cells. The homeostasis of the retinal vessels is important for the maintenance of retinal visual function. Neovascularization is the most common cause of blindness in patients with retinopathy. Previous studies have shown that inflammatory mediators are known key regulators in retinopathy, but their causal link has been elusive. Although inflammation is often thought to arise from inflammatory cells like macrophages, neutrophils, and resident m...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Circulating Retinol-Binding Protein 4 as a Possible Biomarker of Treatment Response for Ankylosing Spondylitis: An Array-Based Comparative Study
ConclusionA dysregulated serum protein profile existed in AS. ADA exerted a considerable but not entire alteration toward the dysregulation. RBP4 could be a biomarker for predicting and monitoring ADA treatment response. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Dihydroartemisinin-Loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy
Recently, chemodynamic therapy (CDT) has represented a new approach for cancer treatment with low toxicity and side effects. Nonetheless, it has been a challenge to improve the therapeutic effect through increasing the amount of reactive oxygen species (ROS). Herein, we increased the amount of ROS agents in the Fenton-like reaction by loading dihydroartemisinin (DHA) which was an artemisinin (ART) derivative containing peroxide groups, into magnetic nanoparticles (MNP), thereby improving the therapeutic effect of CDT. Blank MNP were almost non-cytotoxic, whereas three MNP loading ART-based drugs, MNP-ART, MNP-DHA, and MNP-...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research