Selective Estrogen Receptor Modulator-Like Activities of Herba epimedii Extract and its Interactions With Tamoxifen and Raloxifene in Bone Cells and Tissues
We examined the bone protective effects of HEP and its potential interactions with Selective Estrogen Receptor Modulators (SERMs, such as tamoxifen and raloxifene) as they act via the same ERs. Six-month-old mature Sprague Dawley sham-operated (Sham) or ovariectomized (OVX) rats were treated with either vehicle, 17ß-estradiol (1.0 mg/kg.day), tamoxifen (Tamo, 1.0 mg/kg.day), raloxifene (Ralo, 3.0 mg/kg.day), HEP (0.16 g/kg.day), or its combinations with respective SERMs (HEP + Tamo; HEP + Ralo) for 12 weeks. HEP and SERMs as well as their combinations significantly restored changes in bone mineral...
Source: Frontiers in Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Source Type: research

Panax quinquefolius L. Saponins Protect Myocardial Ischemia Reperfusion No-Reflow Through Inhibiting the Activation of NLRP3 Inflammasome via TLR4/MyD88/NF- κB Signaling Pathway
In this study, we established a MI/R model to investigate whether PQS decrease NR phenomenon via suppression of inflammation. We found that PQS significantly alleviated the symptoms of NR by reducing ischemia, infarction, and NR area; improving cardiac function; preventing pathological morphology changes of myocardium; depressing leukocytes’ aggregation and adhesion; and suppressing the excessive inflammation. Further study demonstrated that PQS remarkably inhibited TLR4, MyD88, p-NF-κB, and NLRP3 inflammasome-associated protein, and these effects could be reversed by LPS. These results indicated that PQS may p...
Source: Frontiers in Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Source Type: research

Timosaponin AIII Induces G2/M Arrest and Apoptosis in Breast Cancer by Activating the ATM/Chk2 and p38 MAPK Signaling Pathways
Timosaponin AIII (TAIII), a steroidal saponin, exerts potent anti-tumor activity in various cancers, especially breast cancer. However, the concrete molecular mechanisms of TAIII against breast cancer are still unclear. Here, we find that TAIII triggers DNA damage, leads to G2/M arrest, and ultimately induces apoptosis in breast cancer both in vitro and in vivo. TAIII induced G2/M phase arrest and apoptosis in MDA-MB-231 and MCF7 cells accompanied with down-regulation of CyclinB1, Cdc2 and Cdc25C. Further data showed that the ATM/Chk2 and p38 pathways were activated representing by up-regulated levels of p-H2A.X and p-p38,...
Source: Frontiers in Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Source Type: research

EFEMP1 Overexpression Contributes to Neovascularization in Age-Related Macular Degeneration
Conclusion: Our findings demonstrate EFEMP1 as a novel biomarker for CNV in AMD, providing a new target for the development of wet AMD-directed pharmaceuticals and diagnostics. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Source Type: research

Unlocking the Mystery of the Therapeutic Effects of Chinese Medicine on Cancer
Over the past decade, the rise of cancer immunotherapy has coincided with a remarkable breakthrough in cancer therapy, which attracted increased interests in public. The scientific community clearly showed that the emergence of immunotherapy is an inevitable outcome of a holistic approach for cancer treatment. It is well established that traditional Chinese medicine (TCM) utilizes the principle of homeostasis and balance to adjust the healthy status of body. TCM treatment toward cancer has a long history, and the diagnosis and treatment of tumors were discussed in the ancient and classical literatures of Chinese medicine, ...
Source: Frontiers in Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Source Type: research

Open Innovation in Medical and Pharmaceutical Research: A Literature Landscape Analysis
Open innovation in medical and pharmaceutical research has grown steadily over the last decade. However, the performance of the published literature in terms of the scientific impact and gaining social media attention remains largely unexplored. The scientific literature of open innovation was examined by means of bibliometric analyses to identify the most prolific authors, organizations, countries, journals, research areas, and recurring terms. By accessing the Web of Science Core Collection and Altmetric electronic databases, citation-related and Altmetric data were evaluated. Public-private partnerships and a selection ...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

The Ginsenoside Exhibits Antiosteoporosis Effects in Ketogenic-Diet-Induced Osteoporosis via Rebalancing Bone Turnover
This study demonstrated that ginsenoside-Rb2 retards bone loss and maintains biomechanics with KD. The underlying mechanism might be that ginsenoside-Rb2 inhibits bone resorption process and induces osteogenic differentiation, providing evidence for ginsenoside as being an alternative option for osteoporosis induced by KD. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Heavy Metal Contaminations in Herbal Medicines: Determination, Comprehensive Risk Assessments, and Solutions
Heavy metal contamination in herbal medicines is a global threat to human beings especially at levels above known threshold concentrations. The concentrations of five heavy metals cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg) and copper (Cu) were investigated using Inductively Coupled Plasma Optical Mass Spectrometry (ICP-MS) with 1773 samples around the world. According to Chinese Pharmacopoeia, 30.51% (541) samples were detected with at least one over-limit metal. The over-limit ratio for Pb was 5.75% (102), Cd at 4.96% (88), As at 4.17% (74), Hg at 3.78% (67), and of Cu, 1.75% (31). For exposure assessment, Pb, Cd...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Tissue Distribution of ACE2 Protein in Syrian Golden Hamster (Mesocricetus auratus) and Its Possible Implications in SARS-CoV-2 Related Studies
The Syrian golden hamster (Mesocricetus auratus) has recently been demonstrated as a clinically relevant animal model for SARS-CoV-2 infection. However, lack of knowledge about the tissue-specific expression pattern of various proteins in these animals and the unavailability of reagents like antibodies against this species hampers these models’ optimal use. The major objective of our current study was to analyze the tissue-specific expression pattern of angiotensin-converting enzyme 2, a proven functional receptor for SARS-CoV-2 in different organs of the hamster. Using two different antibodies (MA5-32307 and AF933),...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Allopregnanolone Decreases Evoked Dopamine Release Differently in Rats by Sex and Estrous Stage
Mesolimbic dopamine transmission is dysregulated in multiple psychiatric disorders, including addiction. Previous studies found that the endogenous GABAergic steroid (3α,5α)-3-hydroxy-5-pregnan-20-one (allopregnanolone) modulates dopamine levels in the nucleus accumbens and prefrontal cortex. As allopregnanolone is a potent positive allosteric modulator of GABAA receptors, and GABAA receptors can regulate dopamine release, we hypothesized that allopregnanolone would reduce phasic fluctuations in mesolimbic dopamine release that are important in learning and reward processing. We used fast-scan cyclic voltammetr...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Effects of Guanxinshutong Capsules as Complementary Treatment in Patients With Chronic Heart Failure: Study Protocol for a Randomized Controlled Trial
This study will show the effects of the specific use of GXST in CHF patients with reduced LVEF. The Research Ethics Committee of the Second Affiliated Hospital of Zhejiang Chinese Medical University has approved this study (2019-Y-003-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1900023877). Our results will be disseminated to the public through peer-reviewed journals, academic conferences, and the Internet. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Saponins in Chinese Herbal Medicine Exerts Protection in Myocardial Ischemia –Reperfusion Injury: Possible Mechanism and Target Analysis
Myocardial ischemia is a high-risk disease among middle-aged and senior individuals. After thrombolytic therapy, heart tissue can potentially suffer further damage, which is called myocardial ischemia-reperfusion injury (MIRI). At present, the treatment methods and drugs for MIRI are scarce and cannot meet the current clinical needs. The mechanism of MIRI involves the interaction of multiple factors, and the current research hotspots mainly include oxidative stress, inflammation, calcium overload, energy metabolism disorders, pyroptosis, and ferroptosis. Traditional Chinese medicine (TCM) has multiple targets and few toxic...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

IQGAP3 Overexpression Correlates With Poor Prognosis and Radiation Therapy Resistance in Breast Cancer
Conclusion: Our findings suggest that high IQGAP3 expression predicts poor prognosis and radioresistance in breast cancer. Therefore, IQGAP3 may be a reliable prognostic biomarker in breast cancer and could be used to identify patients who may benefit from radiotherapy. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Phytosterols: From Preclinical Evidence to Potential Clinical Applications
Phytosterols (PSs) are plant-originated steroids. Over 250 PSs have been isolated, and each plant species contains a characteristic phytosterol composition. A wide number of studies have reported remarkable pharmacological effects of PSs, acting as chemopreventive, anti-inflammatory, antioxidant, antidiabetic, and antiatherosclerotic agents. However, PS bioavailability is a key issue, as it can be influenced by several factors (type, source, processing, preparation, delivery method, food matrix, dose, time of administration into the body, and genetic factors), and the existence of a close relationship between their ch...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Kanglexin protects against cardiac fibrosis and dysfunction in mice by TGF- β1/ERK1/2 noncanonical pathway
Cardiac fibrosis is a common pathological manifestation accompanied by various heart diseases, and antifibrotic therapy is an effective strategy to prevent diverse pathological processes of the cardiovascular system. We currently report the pharmacological evaluation of a novel anthraquinone compound (1,8-dihydroxy-6-methyl-9,10-anthraquinone-3-oxy ethyl succinate) named Kanglexin (KLX), as a potent cardioprotective agent with antifibrosis activity. Our results demonstrated that the administration of KLX by intragastric gavage alleviated cardiac dysfunction, hypertrophy, and fibrosis induced by transverse aortic constricti...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Gut microbiota combined with metabolomics reveals the repeated dose oral toxicity of β-cyclodextrin in mice
Βeta-cyclodextrin (β-CD) with hydrophobic cavity enables formation of inclusion complexes with organic molecules. The formation of host–guest complexes makes application of β-CD popular in many fields, but their interaction with organisms is poorly understood. In the present study, the effect of β-CD on gut microbiota (16S rRNA gene sequencing), serum metabolites (gas chromatography–mass spectrometry platform) and their correlation (Pearson correlation analysis) was investigated after 14 days repeated oral exposure in mice. β-CD did not significantly affect the α-diversity indexes...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Are anticholinergic symptoms a risk factor for falls in older general practice patients with polypharmacy? Study protocol for the development and validation of a prognostic model
This study aims to develop a prognostic model that predicts falls in older general practice patients, to assess the performance of several anticholinergic burden scales, and to quantify the added predictive value of anticholinergic symptoms in this context. Methods Data from two cluster-randomized controlled trials investigating medication optimization in older general practice patients in Germany will be used. One trial (RIME, n = 1,197) will be used for the model development and the other trial (PRIMUM, n = 502) will be used to externally validate the model. A priori, candidate predictors will be selected based on a ...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

The Burden of The Serious and Difficult-to-treat Infections and a New Antibiotic Available: Cefiderocol
Conclusion The results highlighted there appeared to be clinical benefit from cefiderocol in the treatment of infections caused by Gram-negative aerobic microorganisms in adult patients with severe infections and limited treatment options. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

An integrated strategy for effective-component discovery of Astragali Radix in the treatment of lung cancer
Lung cancer is one of the most devastating diseases worldwide with high incidence and mortality worldwide, and the anti-cancer potential of traditional Chinese medicine (TCM) has been gradually recognized by the scientific community. Astragali Radix (AR) is commonly used in traditional Chinese medicine in the treatment of lung cancer and has a certain clinical effect, but effective components and targets are still unclear. In the study, we established an integrated strategy for effective-component discovery of AR in the treatment of lung cancer based on a variety of techniques. Firstly, the effective components and potenti...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Utilisation, availability and price changes of medicines and protection equipment for COVID-19 in India: findings and implications Short title: COVID-19 and price changes of treatments in India
Conclusion: The pandemic has impacted on utilisation and prices of pertinent medicines and PPE in India but moderated by increased scrutiny. Key stakeholder groups can play a role with enhancing evidenced-based approaches and reducing inappropriate purchasing in the future. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Rapid assessment of the potential paucity and price increases for suggested medicines and protection equipment for COVID-19 across developing countries with a particular focus on Africa and the implications
Conclusion: Encouraging to see increases in utilisation of vitamins/ immune boosters and PPE. However, concerns with increased utilisation of antimicrobials needs addressing alongside misinformation, unintended consequences from the pandemic and any appreciable price rise. Community pharmacists and patient organisations can play key role in providing evidence-based advice, helping moderate prices through improved stock management, and helping address unintended consequences of the pandemic. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Pros and Cons of Aspirin for the Primary Prevention of Cardiovascular Events: A Secondary Study of Trial Sequential Analysis using Intention-to-Treat Principles
Background and aims Aspirin leads to substantial benefits for the secondary prevention of cardiovascular disease (CVD). We aimed to cast more light on aspirin’s role for the primary prevention of CVD. Methods Databases were searched for clinical trials comparing aspirin vs. no aspirin use in this meta-analysis. Efficacy and safety profiles were rigorously investigated. Trial sequential analysis (TSA) was used to determine the robustness of the results. Results Fourteen studies with 163 840 participants were eligible (mean follow-up 6.2 y). Aspirin intake was found to be associated with 9%, 13%, and 12% reductions i...
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Machine learning for detection of safety signals from spontaneous reporting system data: example of nivolumab and docetaxel
Conclusions: Machine learning algorithm based on GBM performed better and detected more new ADR signals than traditional disproportionality analysis methods. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Discovery and preclinical development of orally active small molecules that exhibit highly selective follicle stimulating hormone receptor agonism
Conclusions: Two novel oral FSHR-AA, TOP5668 and TOP5300, were found to mimic the biological activity of recombinant human FSH in preclinical studies. Both compounds led to folliculogenesis and superovulation in rat and mice. Specifically, TOP5300 led to a similar number of ovulated oocytes that fertilized developed into hatched blastocysts in mice when compared to rh-FSH. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Source Type: research

Hemokinin-1 as a Mediator of Arthritis-Related Pain via Direct Activation of Primary Sensory Neurons
The tachykinin hemokinin-1 (HK-1) is involved in immune cell development and inflammation, but little is known about its function in pain. It acts through the NK1 tachykinin receptor, but several effects are mediated by a yet unidentified target. Therefore, we investigated the role and mechanism of action of HK-1 in arthritis models of distinct mechanisms with special emphasis on pain. Arthritis was induced by i.p. K/BxN serum (passive transfer of inflammatory cytokines, autoantibodies), intra-articular mast cell tryptase or Complete Freund’s Adjuvant (CFA, active immunization) in wild type, HK-1- and NK1-deficient m...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

The Bruton ’s Tyrosine Kinase Inhibitor Ibrutinib Impairs the Vascular Development of Zebrafish Larvae
Ibrutinib is an orally bioavailable, irreversible selective Bruton’s tyrosine kinase inhibitor that has demonstrated impressive therapeutic effects in patients with B cell malignancies. However, adverse effects, such as bleeding and hypertension, are also reported, implying that studies on the toxicological effect of ibrutinib on living organisms are needed. Here, we have used zebrafish, a successful model organism for studying toxicology, to investigate the influence of ibrutinib during embryogenesis. We found that ibrutinib had potent toxicity on embryonic development, especially vascular development in zebrafish e...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

Determination and Pharmacokinetic Profiles of Four Active Components From Scrophularia ningpoensis Hemsl. in Rats
Acteoside, angoroside C, harpagoside, and cinnamic acid, which are the main bioactive ingredients of Scrophularia ningpoensis Hemsl., have wide clinical use with various biological effects. A new and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established with taxifolin as the internal standard (IS) in this study and was successfully used to study the pharmacokinetic profiles of four active components from S. ningpoensis Hemsl. in rats after sublingual intravenous administration. After protein precipitation with acetonitrile, the mobile phase (consisting of acetonitril...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

Methylene Blue Inhibits the SARS-CoV-2 Spike –ACE2 Protein-Protein Interaction–a Mechanism that can Contribute to its Antiviral Activity Against COVID-19
Due to our interest in the chemical space of organic dyes to identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen of such compounds to assess their inhibitory activity against the interaction between SARS-CoV-2 spike protein and its cognate receptor ACE2, which is the first critical step initiating the viral attachment and entry of this coronavirus responsible for the ongoing COVID-19 pandemic. As part of this, we found that methylene blue, a tricyclic phenothiazine compound approved by the FDA for the treatment of methemoglobinemia and used for other medical ap...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

Dihydropyridine Calcium Channel Blockers Suppress the Transcription of PD-L1 by Inhibiting the Activation of STAT1
Programmed death ligand 1 (PD-L1) which is upregulated in various epithelial tumors, plays a central role in the evasion of the immune system. In addition to monoclonal antibodies that blocking PD1/PD-L1 axis, finding small molecule compounds that can suppress PD-L1 expression might be another substitutable strategy for PD1/PD-L1 based therapy. Here, we found that dihydropyridine calcium channel blockers dose-dependently reduced the expression of PD-L1, both in the cytoplasm and cell surface. IFNγ induced PD-L1 transcription was consistently suppressed by Lercanidipine in 24 h, whereas, the half-life of PD-L1 pr...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

Formononetin Activates the Nrf2/ARE Signaling Pathway Via Sirt1 to Improve Diabetic Renal Fibrosis
In this study, we carried out in vivo experiments in a db/db (diabetic) mouse model and demonstrated that FMN activated the nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway and improved oxidative stress by increasing levels of sirtuin-1 (Sirt1) protein level in renal tissue. We also found that this process reversed the up-regulation of fibronectin (FN) and intercellular adhesion molecule 1 (ICAM-1) and led to an improvement in renal insufficiency. In vitro results further showed that FMN significantly reversed the upregulation of FN and ICAM-1 in glomerular mesangial cells (GMC...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

Allium macrostemon Saponin Inhibits Activation of Platelet via the CD40 Signaling Pathway
Allium macrostemon saponin is a traditional Chinese medicine that exhibits anti-atherosclerosis effects. However, the mechanism of its action has not been fully clarified. Platelet activation induced by CD40L plays an important role in the process of atherosis. In the present study, we demonstrate for the first time that A. macrostemon saponin inhibits platelet activation induced by CD40L. Moreover, the effects of saponin on platelet activation were achieved by activation of the classical CD40L-associated pathway, including the PI3K/Akt, MAPK and NF-κB proteins. In addition, the present study further demonstrated tha...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

The Pharmacological Action of Kaempferol in Central Nervous System Diseases: A Review
In conclusion, we suggest that KPF and some glycosylated derivatives (KPF-3-O-rhamnoside, KPF-3-O-glucoside, KPF-7-O-rutinoside, and KPF-4′-methyl ether) have a multipotential neuroprotective action in CNS diseases, and further studies may make the KPF effect mechanisms in those pathologies clearer. Future in vivo studies are needed to clarify the mechanism of KPF action in CNS diseases as well as the impact of glycosylation on KPF bioactivity. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

Montelukast Use Decreases Cardiovascular Events in Asthmatics
Cysteinyl leukotrienes are proinflammatory mediators with a clinically established role in asthma and a human genetic and preclinical role in cardiovascular pathology. Given that cardiovascular disease has a critical inflammatory component, the aim of this work was to conduct an observational study to verify whether the use of a cysteinyl leukotriene antagonist, namely, montelukast, may protect asthmatic patients from a major cardiovascular event and, therefore, represent an innovative adjunct therapy to target an inflammatory component in cardiovascular disease. We performed an observational retrospective 3-year study on ...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

CPEB4-Promoted Paclitaxel Resistance in Ovarian Cancer In Vitro Relies on Translational Regulation of CSAG2
Conclusion: This study suggests that the drug-resistant protein CSAG2 is translationally induced by CPEB4, which underlies CPEB4-promoted paclitaxel resistance in ovarian cancer in vitro. Thus, interfering CPEB4/CSAG2 axis might be of benefit to overcome paclitaxel-resistant ovarian cancer. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

MYH9 Inhibition Suppresses TGF- β1-Stimulated Lung Fibroblast-to-Myofibroblast Differentiation
Previous cDNA microarray results showed that MYH9 gene expression levels are increased in TGF-β1-stimulated lung fibroblast. Recently, our proteomic results revealed that the expression levels of MYH9 protein are notably upregulated in lung tissues of bleomycin-treated rats. However, whether MYH9 plays a critical role in the differentiation of fibroblast remains unclear. Herein, we demonstrated that TGF-β1 increased MYH9 expression, and siRNA-mediated knockdown of MYH9 and pharmacological inhibition of MYH9 ATPase activity remarkably repressed TGF-β1-induced lung fibroblast-to-myofibroblast differentiation. ...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

Changes in Retinal Structure and Ultrastructure in the Aged Mice Correlate With Differences in the Expression of Selected Retinal miRNAs
Age and gender are two important factors that may influence the function and structure of the retina and its susceptibility to retinal diseases. The aim of this study was to delineate the influence that biological sex and age exert on the retinal structural and ultrastructural changes in mice and to identify the age-related miRNA dysregulation profiles in the retina by gender. Experiments were undertaken on male and female Balb/c aged 24 months (approximately 75–85 years in humans) compared to the control (3 months). The retinas were analyzed by histology, transmission electron microscopy, and age-related m...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

A Novel Insecticidal Spider Peptide that Affects the Mammalian Voltage-Gated Ion Channel hKv1.5
Spider venoms include various peptide toxins that modify the ion currents, mainly of excitable insect cells. Consequently, scientific research on spider venoms has revealed a broad range of peptide toxins with different pharmacological properties, even for mammal species. In this work, thirty animal venoms were screened against hKv1.5, a potential target for atrial fibrillation therapy. The whole venom of the spider Oculicosa supermirabilis, which is also insecticidal to house crickets, caused voltage-gated potassium ion channel modulation in hKv1.5. Therefore, a peptide from the spider O. supermirabilis venom, named Osu1,...
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

Even high-quality CPGs seldom include implementation strategies
Conclusions: Countries with established CPG programs, such as the UK and Colombia, where identified as having the highest number of high-quality CPGs, although CPG implementation content had significant differences. Among high-quality CPGs, the most common implementation strategies were at the professional and organizational levels. There is still room for improvement regarding the implementation strategies report, even among high-quality CPGs, especially concerning monitoring of implementation outcomes and selection of strategies based on relevant implementation barriers. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

DAGL α Inhibition as a Non-invasive and Translational Model of Episodic Headache
Recent findings suggested that Clinical Endocannabinoid Deficiency underlies the pathophysiology of pain disorders, including migraine and headache. In models of medication overuse headache induced by sustained administration of sumatriptan or morphine, 2-AG levels were selectively depleted in the periaqueductal gray (PAG) and anandamide (AEA) increased in the cortex suggesting distinct regulation of the endocannabinoid system during headache pain. These results led to the hypothesis that blockade of DAGL, to reduce 2-AG levels would induce headache-like behaviors as a new, translationally relevant model of episodic headac...
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

SGLT1 Inhibition Attenuates Apoptosis in Diabetic Cardiomyopathy via the JNK and p38 Pathway
In this study, we investigated the influence and underlying mechanism of SGLTI inhibition on DCM.Methods: SGLT1 levels were measured in diabetic patients with similar conditions who visited our hospital from January to December 2019. Wistar male rats (n = 50) were divided into five groups: control, diabetes induced by streptozotocin infusion, and diabetes treated with 0.5, 1.0, or 1.5 mg/kg mizagliflozin via stomach gavage for 12 weeks. H9C2 cardiomyocytes were treated with mizagliflozin and then exposed to a high glucose concentration (30 mmol/L). TUNEL assays were performed, and bcl2, bax, p-p38, p-Erk, p-JNK a...
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

Spatial Lipidomics Reveals Anticancer Mechanisms of Bufalin in Combination with Cinobufagin in Tumor-Bearing Mice
Bufalin (BFL) and cinobufagin (CBF) are the principal bioactive constituents of Chansu, a widely used traditional Chinese medicine (TCM). The synergistic effects of potential active components are responsible for the bioactivities of TCM. Our results showed that the cotreatment with BFL and CBF confers superior anticancer efficacy compared to monotreatment. To reveal the underlying mechanisms of their cotreatment, an integrated method composed of mass spectrometry-based lipidomics and matrix-assisted laser desorption/ionization mass spectrometry imaging was used to delineate the responses of tumor-bearing mice treated with...
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

Efficacy and Safety of Daprodustat for Anemia Therapy in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis
Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

Healthcare Professionals ’ Knowledge of Pharmacogenetics and Attitudes Towards Antimicrobial Utilization in Zambia: Implications for a Precision Medicine Approach to Reducing Antimicrobial Resistance
Introduction: Sub-Saharan Africa and other low- and middle-income countries (LMICs) have the highest rates of antimicrobial resistance (AMR) driven by high rates of antimicrobial utilization. This is a concern as AMR appreciably increases morbidity, mortality and costs. Pharmacogenetics (PGx) and precision medicine are emerging approaches to combat AMR. Consequently, as a first step there is a need to assess AMR knowledge and attitudes, and knowledge of PGx, among healthcare professionals and use the findings to guide future interventions.Methodology: We conducted a cross-sectional study involving 304 healthcare profession...
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

Research on Quality Markers of Guizhi Fuling Prescription for Endometriosis Treatment Based on Gray Correlation Analysis Strategy
In this study, a rapid ultraperformance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS/MS) method was established for Quality Markers investigation on GFP, and a total of 50 potentially bioactive constituents including triterpenoids, paeoniflorin and its derivatives, phenolic acids, and other species were identified based on their retention time, fragmentation pattern, and accurately measured mass value. Furthermore, regularity of recipe composition and gray correlation analysis revealed that all of the characteristic peaks contributed to the treatment of endometriosis. The relative...
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

Electrophysiological Abnormalities in VLCAD Deficient hiPSC-Cardiomyocytes Do not Improve with Carnitine Supplementation
Patients with a deficiency in very long-chain acyl-CoA dehydrogenase (VLCAD), an enzyme that is involved in the mitochondrial beta-oxidation of long-chain fatty acids, are at risk for developing cardiac arrhythmias. In human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs), VLCAD deficiency (VLCADD) results in a series of abnormalities, including: 1) accumulation of long-chain acylcarnitines, 2) action potential shortening, 3) higher systolic and diastolic intracellular Ca2+ concentrations, and 4) development of delayed afterdepolarizations. In the fatty acid oxidation process, carnitine is required for bid...
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

The Anti-Inflammatory Effect of KS23, A Novel Peptide Derived From Globular Adiponectin, on Endotoxin-Induced Uveitis in Rats
Conclusion: The in vivo and in vitro results demonstrated the anti-inflammatory effects of the peptide KS23 and suggested that KS23 is a compelling, novel therapeutic candidate for the treatment of ocular inflammation. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

Transcriptome Analysis of the Inhibitory Effect of Sennoside A on the Metastasis of Hepatocellular Carcinoma Cells
This study has provided new insight into the understanding of the inhibitory effects and potential targets of SA on the metastasis of HCC. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

An Updated Review of the Diagnostic Methods in Delayed Drug Hypersensitivity
Delayed drug hypersensitivity reactions are clinically diverse reactions that vary from isolated benign skin conditions that remit quickly with no or symptomatic treatment, drug discontinuation or even continued drug treatment, to the other extreme of severe cutaneous adverse reactions (SCARs) that are associated with presumed life-long memory T-cell responses, significant acute and long-term morbidity and mortality. Diagnostic “in clinic” approaches to delayed hypersensitivity reactions have included patch testing (PT), delayed intradermal testing (IDT) and drug challenges for milder reactions. Patch and IDT a...
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases
This study explores the various modulators that regulate the activity of SIRT1 and SIRT2, which may further assist in the treatment of neurodegenerative disease. Moreover, we analyze the structure and function of various small molecules that have potential significance in modulating sirtuins, as well as the technologies that advance the targeted therapy of neurodegenerative disease. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research

Trimetazidine in Heart Failure
Heart failure is a systemic syndrome caused by multiple pathological factors. Current treatments do not have satisfactory outcomes. Several basic studies have revealed the protective effect of trimetazidine on the heart, not only by metabolism modulation but also by relieving myocardial apoptosis, fibrosis, autophagy, and inflammation. Clinical studies have consistently indicated that trimetazidine acts as an adjunct to conventional treatments and improves the symptoms of heart failure. This review summarizes the basic pathological changes in the myocardium, with an emphasis on the alteration of cardiac metabolism in the d...
Source: Frontiers in Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Source Type: research