Enhanced Amikacin Diffusion With Ultrasound and Microbubbles in a Mechanically Ventilated Condensed Lung Rabbit Model
In conclusion, this study demonstrates that USMB is a promising method for the targeted delivery of amikacin in mechanically ventilated condensed lung, thus opening new therapeutic fields against lung infections. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 16, 2020 Category: Drugs & Pharmacology Source Type: research

Differential Expression of the Metabotropic P2Y Receptor Family in the Cortex Following Status Epilepticus and Neuroprotection via P2Y1 Antagonism in Mice
In conclusion, our results further support a role for P2Y1-mediated signaling during seizure generation and seizure-induced neurodegeneration, suggesting P2Y1-targeting therapies as novel treatment for drug-refractory status epilepticus. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 16, 2020 Category: Drugs & Pharmacology Source Type: research

Editorial: Molecular Mechanisms and New Therapeutic Targets in Epithelial to Mesenchymal Transition (EMT) and Fibrosis
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 16, 2020 Category: Drugs & Pharmacology Source Type: research

Integrated Plasma and Bile Metabolomics Based on an UHPLC-Q/TOF-MS and Network Pharmacology Approach to Explore the Potential Mechanism of Schisandra chinensis-Protection From Acute Alcoholic Liver Injury
Schisandra chinensis (SC) is a well-known important traditional Chinese medicine (TCM) that has been used to treat liver disease in China for a long time. However, its overall effects and mechanism of action are unclear. The present study aimed to explore the potential mechanism of SC in protection against alcoholic liver injury (ALI). In this research, to enable a full assessment of metabolic changes in ALI in Sprague-Dawley rats and to increase our understanding of physiological changes in normal and pathological states, ultra-high performance liquid chromatography combined with quadrupole time of flight mass spectrometr...
Source: Frontiers in Pharmacology - January 16, 2020 Category: Drugs & Pharmacology Source Type: research

Pimozide Inhibits the Human Prostate Cancer Cells Through the Generation of Reactive Oxygen Species
We examined cell proliferation, colony formation, migration, ROS production, and the expression of antioxidant-related genes after treatment of human prostate cancer PC3 and DU145 cells with pimozide. In addition, histopathology, ROS production, and superoxide dismutase (SOD) activity were analyzed after administering pimozide to TRAMP, a transgenic mouse with prostate cancer. Pimozide increased the generation of ROS in both cell lines and inhibited cell proliferation, migration, and colony formation. Oxidative stress induced by pimozide caused changes in the expression of antioxidant enzymes (SOD1, peroxiredoxin 6, and gl...
Source: Frontiers in Pharmacology - January 16, 2020 Category: Drugs & Pharmacology Source Type: research

Cost-Utility Analysis of Incobotulinumtoxin-A Compared With Conventional Therapy in the Management of Post-Stroke Spasticity in Romania
Conclusions: This therapy should be taken into account when considering rehabilitation options because it is highly cost-effective at
Source: Frontiers in Pharmacology - January 16, 2020 Category: Drugs & Pharmacology Source Type: research

Intracellular ATP Delivery Causes Rapid Tissue Regeneration via Upregulation of Cytokines, Chemokines, and Stem Cells
In this study, we performed a preliminary exploration of the possible mechanisms by focusing on the roles of cytokines, growth factors, and stem cells in this process. Among the 33 adult rabbits, 18 were used for cytokine measurements and the remaining were used for histological and immunohistochemical studies. Four wounds were created on the ventral side of each ear. Two wounds on one side were treated with ATP-vesicles (10 mM ATP), and the other two were treated with controls (normal saline or Regranex). Dressing changes were made daily and the rabbits were sacrificed at 5 h, 12 h, and 1, 2, 3, 4, 6, 9, 15, and 26 days a...
Source: Frontiers in Pharmacology - January 16, 2020 Category: Drugs & Pharmacology Source Type: research

Meta-Analysis of Randomized Controlled Trials Using Botulinum Toxin A at Different Dosages for Urinary Incontinence in Patients With Overactive Bladder
Conclusions: This meta-analysis indicated that BTX-A 200U and 300U are more effective than placebo in the treatment of NDO, with minimal, local, and manageable adverse events. Furthermore, BTX-A 300U and 200U could also improve detrusor compliance of IOAB. However, more RCTs would still be necessary to explore the effect of BTX-A on management of UI in NDO and IOAB patients. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

Connexins in Astrocyte Migration
Astrocytes have long been considered the supportive cells of the central nervous system, but during the last decades, they have gained much more attention because of their active participation in the modulation of neuronal function. For example, after brain damage, astrocytes become reactive and undergo characteristic morphological and molecular changes, such as hypertrophy and increase in the expression of glial fibrillary acidic protein (GFAP), in a process known as astrogliosis. After severe damage, astrocytes migrate to the lesion site and proliferate, which leads to the formation of a glial scar. At this scar-forming ...
Source: Frontiers in Pharmacology - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

Relationship Between Medication Literacy and Medication Adherence in Inpatients With Coronary Heart Disease in Changsha, China
Background: Medication literacy may be associated with medication safety, and medication adherence is critical in treating coronary heart disease. Few studies have explored the association between medication literacy and medication adherence in patients with coronary heart disease. The aim was to investigate the status of medication literacy and medication adherence among Chinese inpatients with coronary heart disease, and explore the association between medication literacy and medication adherence.Methods: The study was a cross-sectional survey. Four hundred seventy inpatients with coronary heart disease were recruited fr...
Source: Frontiers in Pharmacology - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

DeepMalaria: Artificial Intelligence Driven Discovery of Potent Antiplasmodials
Antimalarial drugs are becoming less effective due to the emergence of drug resistance. Resistance has been reported for all available malaria drugs, including artemisinin, thus creating a perpetual need for alternative drug candidates. The traditional drug discovery approach of high throughput screening (HTS) of large compound libraries for identification of new drug leads is time-consuming and resource intensive. While virtual in silico screening is a solution to this problem, however, the generalization of the models is not ideal. Artificial intelligence (AI), utilizing either structure-based or ligand-based approaches,...
Source: Frontiers in Pharmacology - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

Evolution of Ethical Principles in the Practice of Pharmaceutical Medicine From a UK Perspective
Pharmaceutical medicine has evolved to be a distinct medical scientific discipline over time. Pharmaceutical medicine has distinctive features related to complex innovative medicines development activities in an often commercially focused competitive environment. This sometimes uneasy mix of professionalism and commercialisation demands of its medical and scientific researchers alike, a focus on strict adherence to ethical standards, guidelines, practices and behaviors in the interest of delivering new, effective, high-quality lifesaving and life-enhancing medicines quickly and reliably to patients in need. To support the ...
Source: Frontiers in Pharmacology - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

Efficacy and Safety of Chemotherapy Regimens in Advanced or Metastatic Bladder and Urothelial Carcinomas: An Updated Network Meta-Analysis
Conclusions: In our analysis, PGC was superior to MVAC and GC in only the ORR results and superior to GC in the OS and PFS results but was not significantly different from MVAC. More individualized therapies with targeted drugs need to be studied. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

Pedunculopontine Nucleus Degeneration Contributes to Both Motor and Non-Motor Symptoms of Parkinson ’s Disease
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by hypokinetic motor features; however, patients also display non-motor symptoms like sleep disorders. The standard treatment for PD is dopamine replacement with L-DOPA; however, symptoms including gait deficits and sleep disorders are unresponsive to L-DOPA. Notably, these symptoms have been linked to aberrant activity in the pedunculopontine nucleus (PPN). Of late, clinical trials involving PPN deep brain stimulation (DBS) have been employed to alleviate gait deficits. Although preclinical evidence implicating PPN cholinergic neurons in gait dys...
Source: Frontiers in Pharmacology - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review
Numerous studies have shown that berberine and its derivatives demonstrate important anti-tumor effects. However, the specific underlying mechanism remains unclear. Therefore, based on systems pharmacology, this review summarizes the information available on the anti-tumor effects and mechanism of berberine and its derivatives. The action and potential mechanism of action of berberine and its derivatives when used in the treatment of complex cancers are systematically examined at the molecular, cellular, and organismic levels. It is concluded that, with further in-depth investigations on their toxicity and efficacy, berber...
Source: Frontiers in Pharmacology - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

Saussureae Involucratae Herba (Snow Lotus): Review of Chemical Compositions and Pharmacological Properties
Saussureae Involucratae Herba is the dried ground part of Saussurea involucrata (Kar. et Kir.) Sch.-Bip, which is also named as “Snow lotus” and being used in traditional Uyghur and/or Chinese medicine. This rare herb can be found at 4,000 m elevation in western part of Tianshan Mountain, Xinjiang China. According to China Pharmacopoeia (2015), the major pharmaceutical values of “Snow lotus” (Xuě liánhuā in Chinese) are alleviating rheumatoid arthritis, accelerating blood circulation and mitigating other “cold” syndromes. Traditionally, the clinical application of “Snow lo...
Source: Frontiers in Pharmacology - January 14, 2020 Category: Drugs & Pharmacology Source Type: research

Pulmonary Toxicity and the Pathophysiology of Electronic Cigarette, or Vaping Product, Use Associated Lung Injury
New emerging tobacco products, especially electronic cigarettes (E-Cig) or electronic nicotine delivery systems (ENDS), have gained a huge popularity, particularly in younger populations. The lack of sufficient evidence-based health effect studies has promoted widespread use/abuse with the assumption that E-Cig or ENDS and/or vaping products are safer and less toxic than conventional tobacco smoking. However, the recent escalation in acute lung injuries and their associated fatalities among ENDS or vaping product users has now brought attention to this silent epidemic via investigation into the constituents of ENDS/vaping ...
Source: Frontiers in Pharmacology - January 14, 2020 Category: Drugs & Pharmacology Source Type: research

Scaffold-Based Gene Therapeutics for Osteochondral Tissue Engineering
Significant progress in osteochondral tissue engineering has been made for biomaterials designed to deliver growth factors that promote tissue regeneration. However, due to diffusion characteristics of hydrogels, the accurate delivery of signaling molecules remains a challenge. In comparison to the direct delivery of growth factors, gene therapy can overcome these challenges by allowing the simultaneous delivery of growth factors and transcription factors, thereby enhancing the multifactorial processes of tissue formation. Scaffold-based gene therapy provides a promising approach for tissue engineering through transfecting...
Source: Frontiers in Pharmacology - January 14, 2020 Category: Drugs & Pharmacology Source Type: research

Thrombin as Key Mediator of Seizure Development Following Traumatic Brain Injury
In conclusion, these observations indicate a synergism between thrombin and mTBI in lowering seizure in the pilocarpine model and possibly aggravating inflammation. We believe that these results will improve the understanding of PTS pathophysiology and contribute to the development of more targeted therapies in the future. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 14, 2020 Category: Drugs & Pharmacology Source Type: research

Comprehensive Survey of Clinical Trials Registration for Melanoma Immunotherapy in the ClinicalTrials.gov
Conclusions: Currently, most of the registered clinical trials for melanoma immunotherapy were interventional open-label trials. Most immunotherapy research hotspots were in the FDA-regulated drug product, and a few trials reported available test results. It is necessary to strengthen the supervision of results and explore and disseminate more effective and safe immunotherapy methods. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 10, 2020 Category: Drugs & Pharmacology Source Type: research

Assessment of the Preventive Effect Against Diabetic Cardiomyopathy of FGF1-Loaded Nanoliposomes Combined With Microbubble Cavitation by Ultrasound
In conclusion, the VVI and RT-MCE techniques can detect left ventricular systolic function and perfusion changes in DM rats, providing a more effective experimental basis for the early detection and treatment evaluation of DCM, which is of great significance for the prevention of DCM. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 10, 2020 Category: Drugs & Pharmacology Source Type: research

Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis
Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activator of NF-kB ligand (RANKL)/Osteoprotegerin (OPG), which then leads to the overactivation of osteoclastogenesis. Tetrandrine, a bis-benzylisoquinoline alkaloid, has been widely used in the treatment of rheumatoid arthritis clinically in China. Here, we demonstrate that tetrandrine significantly prevented ovariectomy-induced bon...
Source: Frontiers in Pharmacology - January 10, 2020 Category: Drugs & Pharmacology Source Type: research

Validation and Reliability of Healthcare Workers ’ Knowledge, Attitude, and Practice Instrument for Uncomplicated Malaria by Rasch Measurement Model
This study assessed the validity and reliability of healthcare workers’ knowledge, attitudes, and practices instrument for uncomplicated malaria (HKAPIUM) for evaluation of healthcare workers’ knowledge, attitudes, and practices (KAP) on uncomplicated malaria management in primary healthcare (PHC) facilities in Plateau state, Nigeria.Methods: Relevant variables from literature, malaria treatment guidelines for Nigeria, and World Health Organization (WHO) were used to generate and present the items for the draft HKAPIUM scale, which was first screened by six experts before administered to 121 respondents who fil...
Source: Frontiers in Pharmacology - January 10, 2020 Category: Drugs & Pharmacology Source Type: research

Perspective of Key Healthcare Professionals on Antimicrobial Resistance and Stewardship Programs: A Multicenter Cross-Sectional Study From Pakistan
This study was intended to determine the attitude of key healthcare professionals (HCPs), including physicians, nurses, and hospital pharmacists, towards AMR and hospital ASPs.Methods: A cross-sectional study design was used to collect data from HCPs employed in public teaching hospitals of Punjab, Pakistan, from January 2019 to March 2019. A cluster-stratified sampling method was applied. Descriptive statistics, Mann Whitney and Kruskal Wallis tests were used for analysis.Results: A response rate of 81.3% (881/1083) for the surveys was obtained. The majority of the physicians (247/410, 60.2%) perceived AMR to be a serious...
Source: Frontiers in Pharmacology - January 10, 2020 Category: Drugs & Pharmacology Source Type: research

Erratum: microRNA Crosstalk Influences Epithelial-to-Mesenchymal, Endothelial-to-Mesenchymal, and Macrophage-to-Mesenchymal Transitions in the Kidney
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 10, 2020 Category: Drugs & Pharmacology Source Type: research

Using Recombinant Human Collagen With Basic Fibroblast Growth Factor to Provide a Simulated Extracellular Matrix Microenvironment for the Revascularization and Attachment of Islets to the Transplantation Region
Islet transplantation is considered a potential therapeutic option to reverse diabetes. The pancreatic basement membrane contains a variety of extracellular matrix (ECM) proteins. The abundant ECM is essential for the survival of transplanted islets. However, the ECM proteins necessary for maintaining islet vascularization and innervation are impaired by enzymatic digestion in the isolation process before islet transplantation, leading to destruction of islet microvessels. These are the primary concern and major barrier for long-term islet survival and function. Thus, it is crucial to create an appropriate microenviro...
Source: Frontiers in Pharmacology - January 10, 2020 Category: Drugs & Pharmacology Source Type: research

Compound 15c, a Novel Dual Inhibitor of EGFRL858R/T790M and FGFR1, Efficiently Overcomes Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance of Non-Small-Cell Lung Cancers
In the past decades, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) had been proved as an effective treatment strategy for the patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, the tolerance for the EGFR-TKI always occurred after continuous administration for a period of time and limiting the application of these drugs. Activation of FGFR1 signaling pathway was one of the important escape mechanisms for EGFR-TKI resistant in NSCLC. Here, a novel dual inhibitor of EGFRL858R/T790M and FGFR1, compound15c, was found and can efficiently overcame the EGFR-TKI resistance via its simu...
Source: Frontiers in Pharmacology - January 10, 2020 Category: Drugs & Pharmacology Source Type: research

Doxorubicin Induces Endotheliotoxicity and Mitochondrial Dysfunction via ROS/eNOS/NO Pathway
Conclusion: Dox produces excess ROS in the mitochondria, thereby weakens the MMP, opens mPTP, activates the ROS-induced ROS release mechanism, induces ROS burst, and leads to mitochondrial dysfunction, which in turn damages VE. Therefore, interrupting any step of the cycles, as mentioned above can end the related vicious cycle and prevent the occurrence and development of injury. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 10, 2020 Category: Drugs & Pharmacology Source Type: research

Necrosulfonamide Ameliorates Neurological Impairment in Spinal Cord Injury by Improving Antioxidative Capacity
In conclusion, our data suggest a close association between the NSA level inhibiting p-MLKL independently of RIP3 phosphorylation and induction of neurological impairment by improving antioxidative capacity after SCI. NSA ameliorates neurological impairment in SCI through inhibiting MLKL-dependent necroptosis. It also provides a theoretical basis for further research and application of NSA in the treatment of SCI. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

Qing-Kai-Ling Injection Induces Immediate Hypersensitivity Reaction via the Activation of Anaphylatoxin C3
Conclusion: QKLI-IHR is complement activation-related pseudoallergy, rather than an IgE-mediated allergy. QKLI activates C3 and might consequently provoke mast cells to release histamine, which is a principal effector of its IHR. The pseudoallergic reaction induced by QKLI was attributed to the extract of Isatidis Radix. This study suggests a potential therapeutic strategy for the prophylaxis and treatment of QKLI-IHR. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

The Incidence and Risk Factors for Adverse Drug Reactions Related to Tanreqing Injection: A Large Population-Based Study in China
Conclusion: TRQ is well tolerated in the general population, yet off-label use is prevalent. Efforts are required to educate prescribers to adhere to the drug label in order to minimize potential patient harm. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

Inhibitory Effects of Columbianadin on Nociceptive Behaviors in a Neuropathic Pain Model, and on Voltage-Gated Calcium Currents in Dorsal Root Ganglion Neurons in Mice
Radix angelicae pubescentis (RAP) has been used in Chinese traditional medicine to treat painful diseases such as rheumatism and headache. A previous study has reported that columbianadin (CBN), a major coumarin in RAP inhibits acute and inflammatory pain behaviors. However, the effects of CBN on neuropathic pain behaviors, and the potential underlying mechanism have not been reported. In the present study, the effects of CBN, compared to another major coumarin of RAP osthole (OST), on oxaliplatin-induced neuropathic pain behaviors and on the voltage-gated calcium currents in small dorsal root ganglion (DRG) neurons were s...
Source: Frontiers in Pharmacology - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

Book Review: Herbal Principles in Cosmetics: Properties and Mechanisms of Action
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

Berberine-Incorporated Shape Memory Fiber Applied as a Novel Surgical Suture
The surgical suture has long been used to reconnect the injured tissues to restore their structure and function. However, its utility remains challenging in many areas, such as surgical site infections and minimally invasive surgeries. Herein, we report a novel surgical suture that possesses both antibacterial activity and shape memory effect to address these issues. In detail, natural antibacterial berberine was incorporated directly into the spinning solution of shape memory polyurethane with a near body transition temperature, and then berberine-containing polyurethane (BP) fibers were prepared by a facile one-step wet-...
Source: Frontiers in Pharmacology - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

Use of Herbal Medicine by Pregnant Women: What Physicians Need to Know
About 80% of the consumers worldwide use herbal medicine (HMs) or other natural products. The percentage may vary significantly (7%–55%) among pregnant women, depending upon social status, ethnicity, and cultural traditions. This manuscript discusses the most common HMs used by pregnant women, and the potential interactions of HMs with conventional drugs in some medical conditions that occur during pregnancy (e.g., hypertension, asthma, epilepsy). It also includes an examination of the characteristics of pregnant HM consumers, the primary conditions for which HMs are taken, and a discussion related to the potential t...
Source: Frontiers in Pharmacology - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

Medicinal Plant Analysis: A Historical and Regional Discussion of Emergent Complex Techniques
The analysis of medicinal plants has had a long history, and especially with regard to assessing a plant’s quality. The first techniques were organoleptic using the physical senses of taste, smell, and appearance. Then gradually these led on to more advanced instrumental techniques. Though different countries have their own traditional medicines China currently leads the way in terms of the number of publications focused on medicinal plant analysis and number of inclusions in their Pharmacopoeia. The monographs contained within these publications give directions on the type of analysis that should be performed, and f...
Source: Frontiers in Pharmacology - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

Overexpression of Kr üppel-Like Factor 4 Suppresses Migration and Invasion of Non-Small Cell Lung Cancer Through c-Jun-NH2-Terminal Kinase/Epithelial-Mesenchymal Transition Signaling Pathway
Krüppel-like factor 4 (KLF4) is a transcription factor and plays a vital role in cancer initiation and development. However, the role of Krüppel-like factor 4 in the metastasis of non-small cell lung cancer (NSCLC) is not clear. Here, we demonstrated that the expression of Krüppel-like factor 4 was significantly decreased in human non-small cell lung cancer tissues compared with that in normal tissues using Western blot. We performed immunohistochemical staining and observed the decreased expression of Krüppel-like factor 4 in human lung cancer tissues, and metastatic tumor tissues located in the trache...
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

Nephrotoxicity in a Patient With Inadequate Pain Control: Potential Role of Pharmacogenetic Testing for Cytochrome P450 2D6 and Apolipoprotein L1
A case is presented which demonstrates the perils of opioid inefficacy and how pharmacogenomic testing may have prevented nonsteroidal anti-inflammatory drug (NSAID)-induced nephrotoxicity and progression to chronic kidney disease (CKD). A 62 year-old female with back pain was treated with tramadol and hydrocodone; however, neither proved effective. Consequently, to control her pain, she resorted to cocaine, marijuana, and high dose nonsteroidal anti-inflammatory drugs (NSAIDs). She eventually developed CKD. To identify CKD contributors, she underwent genotyping for Apolipoprotein L1 (APOL1), a known risk factor of CKD, as...
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

Microarray Expression Profiling and Raman Spectroscopy Reveal Anti-Fatty Liver Action of Berberine in a Diet-Induced Larval Zebrafish Model
Conclusion: BBR can significantly improve hepatic steatosis in HCD-fed zebrafish larvae. Its mechanisms might be associated with the regulation of lipid metabolism, oxidative stress, and iron homeostasis. Raman imaging in larval zebrafish might become a useful tool for drug evaluation. Mainly, the gene expression profiles provide molecular information for BBR on the prevention and treatment of pediatric NAFLD. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

Ethoxysanguinarine, a Novel Direct Activator of AMP-Activated Protein Kinase, Induces Autophagy and Exhibits Therapeutic Potential in Breast Cancer Cells
Ethoxysanguinarine (Eth) is a benzophenanthridine alkaloid extracted from Macleaya cordata (Willd) R. Br. It possesses antibacterial and antiviral activities and offers therapeutic benefits for the treatment of respiratory syndrome virus-induced cytopathic effects. However, the effect of Eth on human tumors and its pharmacological effects remain to be elucidated, together with its cellular target. Here, we examined the effects of Eth on breast cancer (BC) cells. We found that at low doses, Eth strongly inhibited the viability of BC cell lines and induced autophagy. Mechanistic studies showed that Eth induced autophagy by u...
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

Type 2 β Corticotrophin Releasing Factor Receptor Forms a Heteromeric Complex With Dopamine D1 Receptor in Living Cells
In conclusion, our results show that CRF2β forms a stable heteromeric protein complex with D1R, a potential new therapeutic target in tissues where both receptors are co-expressed, such as the septum in the brain, and heart, kidney, and skeletal muscle in the periphery. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

Modulation of Cytokine-Induced Astrocytic Endothelin-1 Production as a Possible New Approach to the Treatment of Multiple Sclerosis
Conclusions: ET-1 secretion by astrocytoma cells was only stimulated by the pro-inflammatory cytokines IL-1β and TNF-α. Fluoxetine, simvastatin, and resveratrol significantly inhibited this IL-1β- and TNF-α-induced ET-1 production. Simvastatin and resveratrol significantly reduced ET-1 mRNA levels, indicating an effect at the level of transcription. Fluoxetine significantly reduced endothelin converting enzyme-1 mRNA levels, suggesting and effect at the level of protein-processing. The required concentrations of simvastatin (>0.1 µM) and resveratrol (>10 µM) cannot be achieved in hum...
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

Narrowing the Gap Between In Vitro and In Vivo Genetic Profiles by Deconvoluting Toxicogenomic Data In Silico
Toxicogenomics (TGx) is a powerful method to evaluate toxicity and is widely used in both in vivo and in vitro assays. For in vivo TGx, reduction, refinement, and replacement represent the unremitting pursuit of live-animal tests, but in vitro assays, as alternatives, usually demonstrate poor correlation with real in vivo assays. In living subjects, in addition to drug effects, inner-environmental reactions also affect genetic variation, and these two factors are further jointly reflected in gene abundance. Thus, finding a strategy to factorize inner-environmental factor from in vivo assays based on gene expression levels ...
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

Systemic Evaluation on the Pharmacokinetics of Platinum-Based Anticancer Drugs From Animal to Cell Level: Based on Total Platinum and Intact Drugs
In this study, we conduct a systemic evaluation on the pharmacokinetics of three platinum analogues at animal and cell levels, with quantification of both total platinum and intact drugs. A detailed animal study to address and compare the different pharmacokinetic behaviors of three platinum analogues has been conducted in three biological matrices: blood, plasma, and ultrafiltrate plasma. Carboplatin showed an obviously different pharmacokinetic characteristic from cisplatin and oxaliplatin. On the one hand, carboplatin has the highest proportion of Pt distribution in ultrafiltrate plasma. On the other hand, carboplatin h...
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

Genetics of Non-Alcoholic Fatty Liver and Cardiovascular Disease: Implications for Therapy?
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. The most common cause of mortality in NAFLD is cardiovascular disease (CVD), and a key of focus in drug development is to discover therapies that target both liver injury and CVD risk. NAFLD and CVD are complex disease spectra with complex heritability patterns. Nevertheless, genome wide association studies and meta-analyses of these have identified genetic loci that are associated with increased risk of relevant pathological features of disease or clinical endpoints. This review focuses on the genetic risk loci identifie...
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

In Vitro Antioxidant, Anti-Inflammatory and Skin Permeation of Myrsine africana and Its Isolated Compound Myrsinoside B
Dermal aging is characterized by states of oxidative stress, chronic inflammation, and abnormal proteolytic degradation due to the action of hydrogen peroxide, superoxide, 5-lipoxygenase, and elastase, respectively. Noteworthy elastase inhibition has previously been reported, and so this study aimed to investigate the ability of Myrsine africana and myrsinoside B to reduce the activity of hydrogen peroxide, superoxide, and 5-lipoxygenase as supplementary mechanisms of action by which M. africana may reduce the appearance of wrinkles. The use of maltose microneedles were also investigated as a means to enhance the delivery ...
Source: Frontiers in Pharmacology - January 8, 2020 Category: Drugs & Pharmacology Source Type: research

Xuebijing Injection Maintains GRP78 Expression to Prevent Candida albicans –Induced Epithelial Death in the Kidney
Sepsis and septic shock threaten the survival of millions of patients in the intensive care unit. Secondary fungal infections significantly increased the risk of mortality in sepsis patients. Chinese medicine Xuebijing injection (XBJ) has been routinely used as an add-on treatment to sepsis and septic shock in China. Our network pharmacology analysis predicted that XBJ also influences fungal infection, consisting with results of pioneer clinical studies. We conducted in vivo and in vitro experiments to verify this prediction. To our surprise, XBJ rescued mice from lethal Candida sepsis in a disseminated Candida albicans in...
Source: Frontiers in Pharmacology - January 7, 2020 Category: Drugs & Pharmacology Source Type: research

Efficacy and Safety of Sodium Tanshinone IIA Sulfonate Injection on Hypertensive Nephropathy: A Systematic Review and Meta-Analysis
Background: Sodium tanshinone IIA sulfonate (STS) injection, the extractive of traditional Chinese medicine Danshen, is supposed to be a supplementary treatment in hypertensive nephropathy.Objectives: To evaluate the efficacy and safety of STS in treatment of hypertensive nephropathy.Methods: We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan-fang database, Chinese Biomedicine Database (CBM), PubMed, Embase, Web of Science, and Cochrane Library from their inception to December 2018. All studies were screened by two reviewers according to the inclusion ...
Source: Frontiers in Pharmacology - December 24, 2019 Category: Drugs & Pharmacology Source Type: research

Terlipressin Versus Norepinephrine for Septic Shock: A Systematic Review and Meta-Analysis
Conclusions: Current results suggest that terlipressin showed no added survival benefit for septic shock when compared with norepinephrine, while terlipressin could decrease heart rate in the late phase of septic shock compared with norepinephrine without further liver and kidney injury.Systematic Review Registration: PROSPERO (ID: CRD42019128743). Available online at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42019128743. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 24, 2019 Category: Drugs & Pharmacology Source Type: research

Retraction: DEAD-Box Helicase 5 Interacts With Transcription Factor 12 and Promotes the Progression of Osteosarcoma by Stimulating Cell Cycle Progression
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 23, 2019 Category: Drugs & Pharmacology Source Type: research