Impact of DAA Treatment on Cardiovascular Disease Risk in Chronic HCV Infection: An Update
Hepatitis C virus (HCV) infection is a systemic disease associated with multiple significant extrahepatic manifestations. Emerging studies indicate association between the HCV infection and a higher incidence of major adverse cardiovascular events such as: coronary artery disease, heart failure, stroke and peripheral artery disease, when compared to general population. Atherosclerosis is a common pathophysiologic mechanism of cardiovascular disease (CVD) development which is the leading cause of mortality in the Western world. Proposed mechanisms of HCV-induced atherosclerosis includes systemic inflammation due to the chro...
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Antisense Tissue Factor Oligodeoxynucleotides Protected Diethyl Nitrosamine/Carbon Tetrachloride-Induced Liver Fibrosis Through Toll Like Receptor4-Tissue Factor-Protease Activated Receptor1 Pathway
In conclusion, we reported that blockage of TF expression by TFAS improved inflammatory and fibrotic changes associated with CCl4+DEN intoxication. In addition, we explored the potential crosslink between the TF, PAR1 and TLR4 in liver fibrogenesis. These findings offer a platform on which recovery from liver fibrosis could be mediated through targeting TF expression. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells
In this study, we mainly explore the molecular mechanism of ROS-induced CD13 expression using hepatocarcinoma cells as the research object. We show that the drug of fluorouracil (5FU), epirubicin (EPI) and gemcitabine (GEM) can induce ROS generation, activate Ets2 and promote CD13 expression. Meanwhile, CD13 can activate NRF1 and up-regulate ROS scavenging genes transcription, such as SOD1, GPX1, GPX2 and GPX3, leading to down-regulation of intracellular ROS level and reducing the sensitivity of cells to chemotherapy agent. We also detected the anti-tumor effect of the combination therapy, CD13 inhibitor ubenimex and a var...
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Microbiome-Metabolomics Analysis Reveals the Protection Mechanism of α-Ketoacid on Adenine-Induced Chronic Kidney Disease in Rats
Conclusion:α-Ketoacid has a reno-protective effect against adenine-induced CKD, which may be mediated regulation of serum metabolic profiles via affecting intestinal microbial community. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Maternal Nicotine Exposure Alters Hippocampal Microglia Polarization and Promotes Anti-inflammatory Signaling in Juvenile Offspring in Mice
In this study, we explored the impact of nicotine on the microglia during the development of hippocampus. Developmental nicotine exposure in a mouse model was conducted by supplementing nicotine in the drinking water to mother mice during gestation and lactation period. We found that juvenile offspring with maternal nicotine exposure presented physical and neurobehavioral development delay and an increase in anxiety-like behavior in the open field test on postnatal day (PND) 20. To further detect possible developmental neurotoxic effects of nicotine in offspring and underlying mechanism, whole genome microarray analysis of...
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Synergistic Effect of Cefazolin Plus Fosfomycin Against Staphylococcus aureus in vitro and in vivo in an Experimental Galleria mellonella Model
Conclusion: If susceptibility to fosfomycin is either confirmed or can be assumed based on local resistance patterns, combination therapy with cefazolin plus fosfomycin could be a valuable treatment option for empirical as well as targeted therapy of S. aureus and MRSA infections. Future studies proving the clinical significance of this combination therapy are therefore warranted. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Tibetan Medicine Duoxuekang Capsule Ameliorates High-Altitude Polycythemia Accompanied by Brain Injury
Conclusion: Together, the cerebral protection elicited by DXK was due to the decrease of hematological index, suppressing EPO, by affecting the MAPK signaling pathway in oxidative damage, and regulating the RAS signaling pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Histamine can be Formed and Degraded in the Human and Mouse Heart
Histamine is metabolized by several enzymes in vitro and in vivo. The relevance of this metabolism in the mammalian heart in vivo is unclear. However, histamine can exert positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H2-histamine receptors. In transgenic mice (H2-TG) that overexpress the human H2 receptor in cardiomyocytes but not in wild-type littermate mice (WT), histamine induced PIE and PCE in isolated left or right atrial preparations. These H2-TG were used to investigate the putative relevance of histamine degrading enzymes in the mammalian heart. Histidine, the precursor of h...
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages
In conclusion, our experimental results demonstrate that zerumbone effectively attenuates the LPS-induced inflammatory response in macrophages both in vitro and ex vivo by suppressing the activation of the ERK-MAPK and NF-κB signaling pathways as well as blocking the activation of the NLRP3 inflammasome. These results imply that zerumbone may be beneficial for treating sepsis and inflammasome-related diseases. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Integrated Strategy of Network Pharmacological Prediction and Experimental Validation Elucidate Possible Mechanism of Bu-Yang Herbs in Treating Postmenopausal Osteoporosis via ESR1
In conclusion, the current study suggested that Bu-Yang herbs are the most useful TCM herbs in treating PMOP. Furthermore, the integrated strategy of network pharmacology prediction with experimental validation suggested that BYD exerted its anti-PMOP via ESR1 and the downstream mechanism might be activation of the β-catenin signaling pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Cinnamomum Species: Bridging Phytochemistry Knowledge, Pharmacological Properties and Toxicological Safety for Health Benefits
In conclusion, the obtained results from preclinical studies and clinical trials, as well as reduced side effects provide insights into future research of new drugs based on extracts and bioactive compounds from Cinnamomum plants. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Chemical Composition, Diuretic, and Antityrosinase Activity of Traditionally Used Romanian Cerasorum stipites
Cherry stems (CS) represent a by-product intensively used in Eastern European countries as a traditional remedy for urinary tract disorders. Ethnopharmacological evidences sustain the use of CS as aqueous preparations (infusion and decoction), but few data were previously reported about phytochemical profile and pharmacological potential of CS hydroalcoholic extracts. In this regard, we aimed to evaluate the phenolic profile, in vitro antioxidant and tyrosinase inhibitory potential, and in vivo diuretic activity of 70% hydroethanolic cherry stems extract and cherry stems decoction (CSD). LC-DAD-ESI/MSn analysis revealed th...
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Derivation of a Human In Vivo Benchmark Dose for Perfluorooctanoic Acid From ToxCast In Vitro Concentration –Response Data Using a Computational Workflow for Probabilistic Quantitative In Vitro to In Vivo Extrapolation
A computational workflow which integrates physiologically based kinetic (PBK) modeling, global sensitivity analysis (GSA), approximate Bayesian computation (ABC), and Markov Chain Monte Carlo (MCMC) simulation was developed to facilitate quantitative in vitro to in vivo extrapolation (QIVIVE). The workflow accounts for parameter and model uncertainty within a computationally efficient framework. The workflow was tested using a human PBK model for perfluorooctanoic acid (PFOA) and high throughput screening (HTS) in vitro concentration–response data, determined in a human liver cell line, from the ToxCast/Tox21 databas...
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Reduction of Matrix Metallopeptidase 13 and Promotion of Chondrogenesis by Zeel T in Primary Human Osteoarthritic Chondrocytes
This study aimed to explore these effects further to better understand the mode of action of Ze14 on human OA chondrocytes in vitro.Methods: Primary chondrocytes were obtained from the knees of 19 OA patients and cultured either as monolayers or in alginate beads. The cultures were treated with 20% or 10% (v/v) Ze14 or placebo. For RNA-seq, reads were generated with Illumina NextSeq5000 sequencer and aligned to the human reference genome (UCSC hg19). Differential expression analysis between Ze14 and placebo was performed in R using the DESeq2 package. Protein quantification by ELISA was performed on selected genes from the...
Source: Frontiers in Pharmacology - May 11, 2021 Category: Drugs & Pharmacology Source Type: research

Assessment of Anti-Hypertensive Drug Adherence by Serial Aldosterone-To-Renin Ratio Measurement
In conclusion, the measurement of ΔARR is a powerful test, cheap and widely available to accurately identify the non-adherence to RAAS inhibitors treatment. Herein we propose the implementation of ΔARR in clinical practice through a multi-step flow-chart for the management of patients with uncontrolled blood pressure, with identification of those suspected of non-adherence, reserving therapeutic drug monitoring for non-adherence confirmation. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Repurposing Pharmaceuticals Previously Approved by Regulatory Agencies to Medically Counter Injuries Arising Either Early or Late Following Radiation Exposure
The increasing risks of radiological or nuclear attacks or associated accidents have served to renew interest in developing radiation medical countermeasures. The development of prospective countermeasures and the subsequent gain of Food and Drug Administration (FDA) approval are invariably time consuming and expensive processes, especially in terms of generating essential human data. Due to the limited resources for drug development and the need for expedited drug approval, drug developers have turned, in part, to the strategy of repurposing agents for which safety and clinical data are already available. Approval of drug...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Polyphyllin Ⅲ-Induced Ferroptosis in MDA-MB-231 Triple-Negative Breast Cancer Cells can Be Protected Against by KLF4-Mediated Upregulation of xCT
Ferroptosis, which is characterized by the accumulation of intracellular iron and subsequent lipid peroxidation, is a newly discovered form of regulated cell death and plays an important role in tumor suppression. Herein, we showed that Polyphyllin III, which is a major saponin extracted from Paris polyphylla rhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. ACSL4 deletion partly attenuated Polyphyllin III-induced ferroptosis. Polyphyllin III treatment also induced KLF4-mediated protec...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations
Low quality of life and life-threatening conditions often demand pharmacological screening of lead compounds. A spectrum of pharmacological activities has been attributed to pyrazole analogs. The substitution, replacement, or removal of functional groups on a pyrazole ring appears consistent with diverse molecular interactions, efficacy, and potency of these analogs. This mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of some pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs. Numerous interactions of t...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Herbal Medicine “Shulifenxiao” Formula for Nephrotic Syndrome of Refractory Idiopathic Membranous Nephropathy
This study aims to evaluate the effectiveness of Chinese herbal medicine, Shulifenxiao formula, as a promising regimen.Methods: A total of 31 RIMN patients resistant to corticosteroid or immunosuppressive agents were retrospectively analyzed. Shulifenxiao treatment lasted a minimum of 12°months in all patients and extended to 24°months in 11 patients. The primary outcomes [the complete remission (CR) and partial remission (PR)] and secondary outcomes (the serum creatinine and estimated glomerular filtration rate (eGFR) levels) were measured at 6, 12, 18, and 24°months.Results: The data provided an average follo...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

β-Asarone Ameliorates β-Amyloid–Induced Neurotoxicity in PC12 Cells by Activating P13K/Akt/Nrf2 Signaling Pathway
In conclusion, β-asarone could exert neuroprotective effects by modulating the P13K/Akt/Nrf2 signaling pathway. β-asarone might be a promising therapy for AD. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Comparative Efficacy of Oral Chinese Patent Medicine for Chronic Prostatitis/Chronic Pelvic Pain Syndrome With Sexual Dysfunction: A Bayesian Network Meta-Analysis of Randomized Controlled Trials
Conclusion: Based on the NMA, QLSTC, CRYSG, SGYYC, LWDHP/YGC, QLBXC plus WM demonstrated the maximum probability of being the optimal therapies. Owing to the limitations of this research, these results should be confirmed by elaborate RCTs.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021224060]. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Association of NQO2 With UDP-Glucuronosyltransferases Reduces Menadione Toxicity in Neuroblastoma Cells
The balance between detoxification and toxicity is linked to enzymes of the drug metabolism Phase I (cytochrome P450 or oxidoreductases) and phase II conjugating enzymes (such as the UGTs). After the reduction of quinones, the product of the reaction, the quinols—if not conjugated—re-oxidizes spontaneously to form the substrate quinone with the concomitant production of the toxic reactive oxygen species (ROS). Herein, we documented the modulation of the toxicity of the quinone menadione on a genetically modified neuroblastoma model cell line that expresses both the quinone oxidoreductase 2 (NQO2, E.C. 1.10.5.1)...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Routine Clinical Practice Treatment Outcomes of Eplerenone in Acute and Chronic Central Serous Chorioretinopathy
Conclusion: This routine clinical practice outcome study did not show evidence of efficacy of eplerenone on resolution of SRF in acute nor chronic CSCR. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

The Analyses of Chemical Components From Oldenlandia hedyotidea (DC.) Hand.-Mazz and Anticancer Effects in vitro
Oldenlandia hedyotidea (DC.) Hand.-Mazz (OH), also known as sweet tea, is a valuable functional food with medicinal properties and is used for the treatment of cold, cough, gastroenteritis, heatstroke, herpes zoster, and rheumatoid arthritis. The phytochemicals in plant-based foods are responsible for the occurrence of these diseases to some extent. However, there is a scarcity of information on the chemical components of OH. We, therefore, aimed to investigate the phytochemical components of OH using ultra high-performance liquid chromatography–mass spectrometry (UHPLC-MS) and UHPLC triple time-of-flight mass spectr...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

The Role of Chinese Herbal Therapy in Methamphetamine Abuse and its Induced Psychiatric Symptoms
Repeated intake of methamphetamine (METH) leads to drug addiction, the inability to control intake, and strong drug cravings. It is also likely to cause psychiatric impairments, such as cognitive impairment, depression, and anxiety. Because the specific neurobiological mechanisms involved are complex and have not been fully and systematically elucidated, there is no established pharmacotherapy for METH abuse. Studies have found that a variety of Chinese herbal medicines have significant therapeutic effects on neuropsychiatric symptoms and have the advantage of multitarget comprehensive treatment. We conducted a systematic ...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Increasing Efficiency of Repetitive Electroacupuncture on Purine- and Acid-Induced Pain During a Three-Week Treatment Schedule
Acupuncture (AP) is an important constituent of the therapeutic repertoire of traditional Chinese medicine and has been widely used to alleviate chronic painful conditions all over the world. We studied in rats the efficiency of electroacupuncture (EAP) applied to the Zusanli acupoint (ST36) as an analgesic treatment over a 3-week period of time on purine (α,β-methylene ATP, dibenzoyl-ATP)- and acid (pH 6.0 medium)-induced pain in the rat paw. The two ATP derivatives stimulated P2X3 and P2X7 receptors, respectively, while the slightly acidic medium stimulated the “acid-sensitive ion channel 3” (ASIC3...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

In-Vitro α-amylase, α-glucosidase Inhibitory Activities and In-Vivo Anti-Hyperglycemic Potential of Different Dosage Forms of Guduchi (Tinospora Cordifolia [Willd.] Miers) Prepared With Ayurvedic Bhavana Process
Guduchi (Tinospora cordifolia [Willd.] Miers) is a flagship rejuvenating herb of Ayurveda with reported anti-diabetic potential. In the present study, different dosage forms of Guduchi stem (growing on neem tree) were developed by adopting Ayurvedic pharmaceutical process of Bhavana (levigation). Guduchi Churna (GC) was subjected to 07 times Bhavana separately with its own extracted juice, decoction and potable water, and dosage forms namely Svarasa Bhavita Guduchi Churna (SBGC), Kwatha Bhavita Guduchi Churna (KBGC), and Jala Bhavita Guduchi Churna (JBGC) were prepared. The present study was aimed to evaluate the role of B...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Combined Oral and Topical Application of Pumpkin (Cucurbita pepo L.) Alleviates Contact Dermatitis Associated With Depression Through Downregulation Pro-Inflammatory Cytokines
This study aimed to evaluate the efficacy of the combined topical and oral application of pumpkin fruit (Cucurbita pepo L.) extract (PE) in relieving CD associated with chronic stress–induced depression and compare it to the topical pumpkin extract alone and to the standard treatment.Materials and Methods: Forty male albino rats were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks for induction of depression and then exposed to (1-fluoro-2, 4-dinitrofluorobenzene, DNFB) for 2 weeks for induction of CD. Those rats were assigned into 4 groups (n = 10 each); untreated, betamethasone-treated, PE...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Unraveling the Catha edulis Extract Effects on the Cellular and Molecular Signaling in SKOV3 Cells
In conclusion, khat induces significant cellular and molecular changes that could potentially cause a wide range of serious diseases and syndromes. Such an impact could have a heavy burden on the health care system in the countries where khat is consumed. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

A Systematic Review on Comparative Analysis, Toxicology, and Pharmacology of Medicinal Plants Against Haemonchus contortus
Conclusion: This review summarized different medicinal plants owing to nematicidal activities against H. contortus eggs, larvae, and adult worms. Plants like L. viridiflorum, C. citriodora, C. procera, and A. herba-alba, while compounds anethole and carvone having promising nematicidal activities and could be an alternative source for developing novel drugs after further investigation. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

A Novel Role of A2AR in the Maintenance of Intestinal Barrier Function of Eteric Glia from Hypoxia-Induced Injury by Combining with mGluR5
This study shows, for the first time, that hypoxia induces A2AR-mGluR5 interaction in EGCs to protect IEB function via the PKCα pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Exploring the Mechanism of Zhibai Dihuang Decoction in the Treatment of Ureaplasma Urealyticum-Induced Orchitis Based on Integrated Pharmacology
Background: Ureaplasma urealyticum (UU) infection is the most common cause of male infertility. Zhibai Dihuang Decoction (ZBDHD) can improve the rate of forwarding motility sperm, sperm deformity rate, seminal plasma zinc and refined berry sugar levels.Methods: The potential targets of ZBDHD are obtained from The Encyclopedia of Traditional Chinese Medicine (ETCM). Orchitis-related targets were collected from the Genecards and OMIM databases. The Cytoscape and the Database for Annotation, Visualization and Integrated Discovery (DAVID) were utilized to construct and analyzed the networks. Finally, a rat model of orchitis ca...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease
The presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidelines, respectively. An oral dose of 2000 mg/kg to rats for acute toxicity. Furthermore, 5, 10, 20, and 40 mg/kg doses were administered once daily for 28 days in subacute toxicity study. Teratogenicity study was performed with 40 mg/kg due to its excellent anti-Alzheimer results at this dose. SF1 induced a si...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Metabolite Profiling of the Indian Food Spice Lichen, Pseudevernia furfuracea Combined With Optimised Extraction Methodology to Obtain Bioactive Phenolic Compounds
This study is an attempt to find the best extraction methodology with respect to extractive yield, total polyphenolic content (TPC), total flavonoid content and antioxidant activities of lichen P. furfuracea. Two phenolic compounds, atraric acid and olivetoric acid were isolated and quantified in their respective extracts with the aid of reverse phase high performance liquid chromatography (RP-HPLC). The highest concentration of both the compounds, atraric acid (4.89 mg/g DW) and olivetoric acid (11.46 mg/g DW) were found in 70% methanol extract. A direct correlation was also observed between the concentrations o...
Source: Frontiers in Pharmacology - May 10, 2021 Category: Drugs & Pharmacology Source Type: research

Purinergic P2 Receptors: Novel Mediators of Mechanotransduction
Mechanosensing and mechanotransduction are vital processes in mechanobiology and play critical roles in regulating cellular behavior and fate. There is increasing evidence that purinergic P2 receptors, members of the purinergic family, play a crucial role in cellular mechanotransduction. Thus, information on the specific mechanism of P2 receptor-mediated mechanotransduction would be valuable. In this review, we focus on purinergic P2 receptor signaling pathways and describe in detail the interaction of P2 receptors with other mechanosensitive molecules, including transient receptor potential channels, integrins, caveolae-a...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway
Diabetes increases the risk of stroke, exacerbates neurological deficits, and increases mortality. Non-mitogenic fibroblast growth factor 1 (nmFGF1) is a powerful neuroprotective factor that is also regarded as a metabolic regulator. The present study aimed to investigate the effect of nmFGF1 on the improvement of functional recovery in a mouse model of type 2 diabetic (T2D) stroke. We established a mouse model of T2D stroke by photothrombosis in mice that were fed a high-fat diet and injected with streptozotocin (STZ). We found that nmFGF1 reduced the size of the infarct and attenuated neurobehavioral deficits in our mous...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Integrated Pharmacological Analysis on the Mechanism of Fuyou Formula in Treating Precocious Puberty
In this study, we analyze the components and mechanisms of FY in PP, based on the integrated pharmacology. Investigated main constituents, targets, pathways of FY by using an integrative pharmacology, and recognized main constituents by HPLC-MS/MS. Then, observed the levels of Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E2) in danazol-induced PP in Sprague–Dawley (SD) rats. Lastly, retrospective study analyzed the clinical data of 575 patients who were diagnosed PP, treated by the FY, and followed-up in our hospital from 2014–2020. The result that total of 116 important candidate...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Curcumin as a Potential Treatment for COVID-19
Coronavirus disease 2019 (COVID-19) is an infectious disease that rapidly spread throughout the world leading to high mortality rates. Despite the knowledge of previous diseases caused by viruses of the same family, such as MERS and SARS-CoV, management and treatment of patients with COVID-19 is a challenge. One of the best strategies around the world to help combat the COVID-19 has been directed to drug repositioning; however, these drugs are not specific to this new virus. Additionally, the pathophysiology of COVID-19 is highly heterogeneous, and the way of SARS-CoV-2 modulates the different systems in the host remains u...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Pemetrexed-Platinum With or Without Bevacizumab for Chinese Chemo-Naive Advanced Lung Adenocarcinoma Patients: A Real-World Study
This study was conducted to compare the efficacy and safety of pemetrexed–platinum with or without bevacizumab in Chinese chemo-naive advanced lung adenocarcinoma patients in a real-world setting. We retrospectively collected 100 patients who received pemetrexed–platinum with or without bevacizumab (PP, n = 46; Bev+PP, n = 54) until disease progression or unacceptable toxicity. Clinical characteristics of patients were balanced, except for the proportion of stage IV b+c (Bev+PP and PP: 67.4 vs. 37.0%, p = 0.0066). Bev+PP significantly improved the objective response rate (ORR, 65 vs. 30%, p = 0.0004) and progre...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Anti-Inflammatory Effects of Dimethyl Fumarate in Microglia via an Autophagy Dependent Pathway
Dimethyl fumarate (DMF), which has been approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis, is considered to exert anti-inflammatory and antioxidant effects. Microglia maintain homeostasis in the central nervous system and play a key role in neuroinflammation, while autophagy controls numerous fundamental biological processes, including pathogen removal, cytokine production, and clearance of toxic aggregates. However, the role of DMF in autophagy induction and the relationship of this effect with its anti-inflammatory functions in microglia are not well known. In the pr...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Downregulated MicroRNA-327 Attenuates Oxidative Stress –Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway
In conclusion, inhibition of miR-327 improved antioxidative ability and myocardial cell survival via regulating the FGF10/Akt/Nrf2 pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

BYHWD Alleviates Inflammatory Response by NIK-Mediated Repression of the Noncanonical NF- κB Pathway During ICH Recovery
Intracerebral hemorrhage (ICH) is a life-threatening type of stroke that lacks effective treatments. The inflammatory response following ICH is a vital response that affects brain repair and organism recovery. The nuclear factor κB (NF-κB) signaling pathway is considered one of the most important inflammatory response pathways and one of its response pathways, the noncanonical NF-κB signaling pathway, is known to be associated with persistent effect and chronic inflammation. NF-κB–inducing kinase (NIK) via the noncanonical NF-κB signaling plays a key role in controlling inflammation. Her...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

CYP2D6 in the Brain: Potential Impact on Adverse Drug Reactions in the Central Nervous System —Results From the ADRED Study
This study aimed to analyze variability in CYP2D6 activity linked to vigilance-related adverse drug reactions (ADRs) in the CNS. A dataset of N = 2939 ADR cases of the prospective multicenter observational trial in emergency departments (EDs) (ADRED; trial registration: DRKS-ID: DRKS00008979) was analyzed. Dizziness as the most frequent reported CNS ADR symptom (12.7% of patients, n = 372) related to vigilance was chosen as the outcome. The association of dizziness with CYP2D6 activity markers was analyzed. The number of CYP2D6 substrates taken, a CYP2D6 saturation score (no, moderate, and strong saturation), a CYP2D6 satu...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Aldehyde Dehydrogenase 2 Protects Against Lipopolysaccharide-Induced Myocardial Injury by Suppressing Mitophagy
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-induced circulatory and cardiac dysfunction is associated with high mortality rates. Mitophagy, a specific form of autophagy, is excessively activated in lipopolysaccharide-induced myocardial injury. The present study investigated whether aldehyde dehydrogenase 2 (ALDH2) regulates mitophagy in sepsis-induced myocardial dysfunction. After lipopolysaccharide administration, cardiac dysfunction, inflammatory cell infiltration, biochemical indicators of myocardial cell injury, and cardiomyocyte apoptosis were ame...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Ibudilast Attenuates Folic Acid –Induced Acute Kidney Injury by Blocking Pyroptosis Through TLR4-Mediated NF-κB and MAPK Signaling Pathways
Folic acid (FA)-induced renal tubule damage, which is characterized by extensive inflammation, is a common model of acute kidney injury (AKI). Pyroptosis, a pro-inflammatory form of cell death due to the activation of inflammatory caspases, is involved in AKI progression. Ibudilast, a TLR4 antagonist, has been used in the clinic to exert an anti-inflammatory effect on asthma. However, researchers have not explored whether ibudilast exerts a protective effect on AKI by inhibiting inflammation. In the present study, ibudilast reversed FA-induced AKI in mice, as indicated by the reduced serum creatinine and urea nitrogen leve...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Effects of a Common Eight Base Pairs Duplication at the Exon 7-Intron 7 Junction on Splicing, Expression, and Function of OCT1
Organic cation transporter 1 (OCT1, SLC22A1) is localized in the sinusoidal membrane of human hepatocytes and mediates hepatic uptake of weakly basic or cationic drugs and endogenous compounds. Common amino acid substitutions in OCT1 were associated with altered pharmacokinetics and efficacy of drugs like sumatriptan and fenoterol. Recently, the common splice variant rs35854239 has also been suggested to affect OCT1 function. rs35854239 represents an 8 bp duplication of the donor splice site at the exon 7-intron 7 junction. Here we quantified the extent to which this duplication affects OCT1 splicing and, as a consequence,...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Integrated Isogenic Human Induced Pluripotent Stem Cell –Based Liver and Heart Microphysiological Systems Predict Unsafe Drug–Drug Interaction
Three-dimensional (3D) microphysiological systems (MPSs) mimicking human organ function in vitro are an emerging alternative to conventional monolayer cell culture and animal models for drug development. Human induced pluripotent stem cells (hiPSCs) have the potential to capture the diversity of human genetics and provide an unlimited supply of cells. Combining hiPSCs with microfluidics technology in MPSs offers new perspectives for drug development. Here, the integration of a newly developed liver MPS with a cardiac MPS—both created with the same hiPSC line—to study drug–drug interaction (DDI) is reporte...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Falcarindiol Enhances Cisplatin Chemosensitivity of Hepatocellular Carcinoma via Down-Regulating the STAT3-Modulated PTTG1 Pathway
Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy globally and the third leading cause of cancer-related death. Chemotherapy is one of the main methods in treating HCC, while recent studies have found that the resistance of HCC to chemotherapeutic drugs reduces the efficacy of the chemotherapy. Falcarindiol (FAD) is a cytotoxic and anti-inflammatory polyacetylenic oxylipin found in food plants of the carrot family (Apiaceae), while its role in HCC remains to be explored. Here, HCC cells (Huh7 and LM3) were treated with FAD at different doses. Cell proliferation was tested by the cell counting kit...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Clinical Application of Chinese Herbal Injection for Cancer Care: Evidence-Mapping of the Systematic Reviews, Meta-analyses, and Randomized Controlled Trials
Conclusion: The current evidence mapping provides an overview of the outcomes and effects of Chinese herbal injections used in cancer care, and offers information on their clinical application which warrants further evidence-based research in order to inform clinical and policy decision-making. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Phytochemicals as a Complement to Cancer Chemotherapy: Pharmacological Modulation of the Autophagy-Apoptosis Pathway
Bioactive plant derived compounds are important for a wide range of therapeutic applications, and some display promising anticancer properties. Further evidence suggests that phytochemicals modulate autophagy and apoptosis, the two crucial cellular pathways involved in the underlying pathobiology of cancer development and regulation. Pharmacological targeting of autophagy and apoptosis signaling using phytochemicals therefore offers a promising strategy that is complementary to conventional cancer chemotherapy. In this review, we sought to highlight the molecular basis of the autophagic-apoptotic pathway to understand its ...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research