Restoration of Proresolution Pathway with Exogenous Resolvin D1 Prevents Sevoflurane-Induced Cognitive Decline by Attenuating Neuroinflammation in the Hippocampus in Rats with Type 2 Diabetes Mellitus
Sevoflurane (SEV), a commonly used volatile anesthetic, has been shown to cause cognitive decline in diabetic rats by aggregating neuroinflammation in the hippocampus, but the underlying mechanisms are unknown. Recent evidence suggests that neuroinflammation could be a consequence of failure to resolve inflammation by specialized pro-resolving lipid mediators including resolvin D1 (RvD1). Here we first examined whether type 2 diabetes mellitus (DM) alters RvD1 proresolution pathway. Diabetic Goto-Kakizaki (GK) rats and non-diabetic Wistar rats received control or 2.6% SEV exposure for 4 h. Seven days after exposure, G...
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Corrigendum: Exploring the Mechanism of Total Flavonoids of Drynariae Rhizoma to Improve Large Bone Defects by Network Pharmacology and Experimental Assessment
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy
In this report, we demonstrate that the activity of TFEB is reduced in the liver of mice fed a high-fat diet. Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB. We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Reynoutrin Improves Ischemic Heart Failure in Rats Via Targeting S100A1
This study investigated the effects of reynoutrin on the improvement of ischemic heart failure (IHF) and its possible mechanism in rats. The rat heart failure model was established by permanently ligating the left anterior descending coronary artery (LAD) and administering different doses of reynoutrin. Cardiac function, inflammatory factors releasing, oxidative stress, cardiomyocytes apoptosis, and myocardial fibrosis were evaluated. Western blotting was used to determine protein expression levels of S100 calcium-binding protein A1 (S100A1), matrix metallopeptidase 2(MMP2), MMP9, phosphorylated (p-) p65, and transforming ...
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Prediction of Rivaroxaban-Rifampin Interaction After Major Orthopedic Surgery: Physiologically Based Pharmacokinetic Modeling and Simulation
Rivaroxaban is commonly used for the prophylaxis of venous thromboembolism (VTE) for patients undergoing major orthopedic surgery. Rivaroxaban is primarily eliminated by hepatic CYP450 metabolism and renal excretion. Rifampin is a commonly used antibiotic for prosthetic joint infections (PJI) and a potent inducer of CYP450 enzymes. Clinical data about drug-drug interactions of rivaroxaban and rifampin are limited. The present study is to describe DDI of rivaroxaban and rifampin in several prosthetic joint infections patients undergoing major orthopedic surgery. We retrospectively identified six patients concomitantly admin...
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome
In conclusion, this study confirmed that MAG alleviates “M1” polarized macrophage-mediated NP cell damage by inactivating the HMGB1-MyD88-NF-κB pathway and NLRP3 inflammasome, which provides a new reference for IDD treatment. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Mechanistic Modeling of a Novel Oncolytic Virus, V937, to Describe Viral Kinetic and Dynamic Processes Following Intratumoral and Intravenous Administration
V937 is an investigational novel oncolytic non-genetically modified Kuykendall strain of Coxsackievirus A21 which is in clinical development for the treatment of advanced solid tumor malignancies. V937 infects and lyses tumor cells expressing the intercellular adhesion molecule I (ICAM-I) receptor. We integrated in vitro and in vivo data from six different preclinical studies to build a mechanistic model that allowed a quantitative analysis of the biological processes of V937 viral kinetics and dynamics, viral distribution to tumor, and anti-tumor response elicited by V937 in human xenograft models in immunodeficient mice ...
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

South African Regulatory Authority: The Impact of Reliance on the Review Process Leading to Improved Patient Access
Conclusion: The comparisons made through this study provided insight into the improvements that have been made through the establishment of SAHPRA and the transition in 2018 from the MCC. The re-engineered processes that have been developed and implemented by SAHPRA to address the backlog in the review of the applications for market authorization have demonstrated a decrease in the overall median approval times. The expansion of these processes into the routine review of medical products will contribute to the enhanced regulatory performance of SAHPRA and patients’ access to new medicines. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Cytokine Release Syndrome Is an Independent Risk Factor Associated With Platelet Transfusion Refractoriness After CAR-T Therapy for Relapsed/Refractory Acute Lymphoblastic Leukemia
Conclusion: We found for the first time that PTR is associated with the CRS grade. Improved knowledge on the mechanisms of PTR after CAR-T therapy is needed to design a rational therapeutic strategy that aims to improve the efficiency of transfusions. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Probiotic Supplementation for Rheumatoid Arthritis: A Promising Adjuvant Therapy in the Gut Microbiome Era
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease that ultimately leads to joint destruction and functional disability. Although the exact etiology of RA is not fully understood, it is well established that gut microbiota (GM) plays a vital role in the pathogenesis of RA, with accumulating evidence suggesting that gut dysbiosis induces a chronic inflammatory response that may be linked to disease development. Of interest, patients with RA have significant changes in the intestinal microbiota compared to healthy controls, and several studies have suggested the use of probiotics as a possible adjuva...
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Enhancement of Insulin/PI3K/Akt Signaling Pathway and Modulation of Gut Microbiome by Probiotics Fermentation Technology, a Kefir Grain Product, in Sporadic Alzheimer ’s Disease Model in Mice
Sporadic Alzheimer’s disease (AD) is the most common neurodegenerative disorder with cognitive dysfunction. Remarkably, alteration in the gut microbiome and resultant insulin resistance has been shown to be connected to metabolic syndrome, the crucial risk factor for AD, and also to be implicated in AD pathogenesis. Thus, this study, we assessed the efficiency of probiotics fermentation technology (PFT), a kefir product, in enhancing insulin signaling via modulation of gut microbiota to halt the development of AD. We also compared its effectiveness to that of pioglitazone, an insulin sensitizer that has been confirme...
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Autophagy Modulators From Chinese Herbal Medicines: Mechanisms and Therapeutic Potentials for Asthma
Asthma has become a global health issue, suffering more than 300 million people in the world, which is a heterogeneous disease, usually characterized by chronic airway inflammation and airway hyperreactivity. Combination of inhaled corticosteroids (ICS) and long acting β-agonists (LABA) can relieve asthma symptoms and reduce the frequency of exacerbations, especially for patients with refractory asthma, but there are limited treatment options for people who do not gain control on combination ICS/LABA. The increase in ICS dose generally provides little additional benefit, and there is an increased risk of side effects....
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Editorial: Imaging Technology in Oncology Pharmacological Research
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Cyp2d6 allele frequency in five malaria vivax endemic areas from brazilian amazon region
Genetic variability was linked with individual responses to treatment and susceptibility to malaria by Plasmodium vivax. Polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. The aim of the study was to investigate whether or not CYP2D6 single nucleotide polymorphisms (SNPs) rs1065852, rs38920-97, rs16947 and rs28371725 are unequally distributed in malaria by Plasmodium vivax individuals from the Brazilian Amazon region. The blood samples were collected from 220 unrelated Plasmodium vivax patients from five different endemic areas. Geno...
Source: Frontiers in Pharmacology - July 23, 2021 Category: Drugs & Pharmacology Source Type: research

Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production
In conclusion, matrine inhibits platelet function, arterial and venous thrombosis, possibly involving inhibition of ROS generation, suggesting that matrine might be used as an antiplatelet agent for treating thrombotic or cardiovascular diseases. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

The Effects of Erchen Decoction on Gut Microbiota and Lipid Metabolism Disorders in Zucker Diabetic Fatty Rats
In this study, we investigated the effects of ECD on obesity, especially lipid metabolism and the composition and function of gut microbiota in Zucker diabetic fatty (ZDF) rats, and explored the correlation between the biomarkers of gut microbiota and metabolite and host phenotype. The results showed that ECD could reduce body weight, improve IR and lipid metabolism, and reduce the concentration of free fatty acids (FFA) released from white adipose tissue (WAT) due to excessive lipolysis by interfering with the insulin receptor substrate 1 (IRS1)/protein kinase B (AKT)/protein kinase A (PKA)/hormone-sensitive triglyceride ...
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

Neferine Ameliorates Sepsis-Induced Myocardial Dysfunction Through Anti-Apoptotic and Antioxidative Effects by Regulating the PI3K/AKT/mTOR Signaling Pathway
This study aims to explore the protective effects of neferine against lipopolysaccharide (LPS)-induced myocardial dysfunction and its mechanisms. The LPS-induced cardiac dysfunction mouse model was employed to investigate the protective effects of neferine. In this study, we demonstrated that neferine remarkably improved cardiac function and survival rate and ameliorated morphological damage to heart tissue in LPS-induced mice. Neferine also improved cell viability and mitochondrial function and reduced cell apoptosis and the production of reactive oxygen species in LPS-treated H9c2 cells. In addition, neferine significant...
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

Recent Progresses in the Treatment of Osteoporosis
Osteoporosis (OP) is a chronic bone disease characterized by aberrant microstructure and macrostructure of bone, leading to reduced bone mass and increased risk of fragile fractures. Anti-resorptive drugs, especially, bisphosphonates, are currently the treatment of choice in most developing countries. However, they do have limitations and adverse effects, which, to some extent, helped the development of anabolic drugs such as teriparatide and romosozumab. In patients with high or very high risk for fracture, sequential or combined therapies may be considered with the initial drugs being anabolic agents. Great endeavors hav...
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

Differential Dermatologic Adverse Events Associated With Checkpoint Inhibitor Monotherapy and Combination Therapy: A Meta-Analysis of Randomized Control Trials
Conclusion: Our meta-analysis demonstrates a better safety profile for PD-1/-L1 inhibitor compared to CTLA-4 inhibitor in terms of pruritus and rash among both monotherapy and multiple combination therapies. PD-L1 inhibitor may contribute to an increased risk of pruritus and rash compared to PD-1 inhibitor. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

A Comparison of Nine Machine Learning Mutagenicity Models and Their Application for Predicting Pyrrolizidine Alkaloids
Random forest, support vector machine, logistic regression, neural networks and k-nearest neighbor (lazar) algorithms, were applied to a new Salmonella mutagenicity dataset with 8,290 unique chemical structures utilizing MolPrint2D and Chemistry Development Kit (CDK) descriptors. Crossvalidation accuracies of all investigated models ranged from 80 to 85% which is comparable with the interlaboratory variability of the Salmonella mutagenicity assay. Pyrrolizidine alkaloid predictions showed a clear distinction between chemical groups, where otonecines had the highest proportion of positive mutagenicity predictions and monoes...
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

Pimpinellin Inhibits Collagen-induced Platelet Aggregation and Activation Through Inhibiting Granule Secretion and PI3K/Akt Pathway
This study found that pimpinellin pretreatment effectively inhibited collagen-induced platelet aggregation, but did not alter ADP- and thrombin-induced aggregation. Platelets pretreated with pimpinellin showed reduced α granule (CD62) level and secretion of dense granule (ATP release). Pimpinellin-treated platelets also exhibited decreased clot reaction and TxB2 production. Pimpinellin pretreatment suppressed adhesion and spreading of human platelets on the fibrinogen coated surface. Analysis of tail bleeding time of mice administered with pimpinellin (40 mg/kg) revealed that pimpinellin did not change tail blee...
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

H2S Donor and Bone Metabolism
Hydrogen sulfide (H2S) has been recognized as the third gasotransmitter, following nitric oxide and carbon monoxide, and it exerts important biological effects in the body. Growing evidence has shown that H2S is involved in many physiological processes in the body. In recent years, much research has been carried out on the role of H2S in bone metabolism. Bone metabolic diseases have been linked to abnormal endogenous H2S functions and metabolism. It has been found that H2S plays an important role in the regulation of bone diseases such as osteoporosis and osteoarthritis. Regulation of H2S on bone metabolism has many intera...
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

rhKGF-2 Attenuates Smoke Inhalation Lung Injury of Rats via Activating PI3K/Akt/Nrf2 and Repressing FoxO1-NLRP3 Inflammasome
This study aims to probe the protective effect and mechanism of recombinant human keratinocyte growth factor 2 (rhKGF-2) against smoke inhalation-induced lung injury (SILI) in rats. The SILI was induced in rats using a smoke exposure model, which were then treated with rhKGF-2. The rat blood was collected for blood-gas analysis, and the levels of inflammatory factors and oxidative stress markers in the plasma were measured. The rat lung tissues were collected. The pathological changes and cell apoptosis were determined by hematoxylin-eosin (HE) staining and TdT-mediated dUTP nick end labeling (TUNEL) assay, and the PI3K/Ak...
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

First-in-Human, Double-Blind, Randomized, Placebo-Controlled Trial of TQ-F3083, a New Dipeptidyl Peptidase-4 Inhibitor, in Healthy Chinese Adults
Conclusion: TQ-F3083 was well tolerated in healthy Chinese adults, and the pharmacokinetic and pharmacodynamic characteristics support further evaluation of TQ-F3083 in a trial in T2DM patients. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

The Depolarization-Evoked, Ca2+-Dependent Release of Exosomes From Mouse Cortical Nerve Endings: New Insights Into Synaptic Transmission
Whether exosomes can be actively released from presynaptic nerve terminals is a matter of debate. To address the point, mouse cortical synaptosomes were incubated under basal and depolarizing (25 mM KCl-enriched medium) conditions, and extracellular vesicles were isolated from the synaptosomal supernatants to be characterized by dynamic light scattering, transmission electron microscopy, Western blot, and flow cytometry analyses. The structural and biochemical analysis unveiled that supernatants contain vesicles that have the size and the shape of exosomes, which were immunopositive for the exosomal markers TSG101, fl...
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

Effect of Osimertinib in Combination With Chemotherapy and Bevacizumab for Untreated Epidermal Growth Factor Receptor –Mutated Advanced Non-Small-Cell Lung Cancer: Case Report
Conclusions: The patient benefited from treatment with osimertinib in combination with chemotherapy and bevacizumab. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

Colony-Stimulating Factors on Mobilizing CD34+ Cells and Improving Neurological Functions in Patients With Stroke: A Meta-Analysis and a Systematic Review
Conclusion: Our study consolidates the security of CSF administration for its exerting no effect on detrimental outcomes. It has proven to be effective in elevating CD34+ cell counts in periphery blood at day 5, indicating CSF may participate in stroke recovery, but its efficacy in stroke recovery remains detected. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

Exploring the Mechanism of Indigo Naturalis in the Treatment of Ulcerative Colitis Based on TLR4/MyD88/NF- κB Signaling Pathway and Gut Microbiota
Conclusion: Indigo and indirubin are one of the main anti-UC components of indigo naturalis. INN could regulate intestinal flora, reduce inflammation, repair intestinal mucosa, and improve the physiological status of DSS-induced UC mice and its anti-UC mechanism may be involved in inhibiting TLR4/MyD88/NF-κB signal transduction. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

Modulation of HMGB1 Release in APAP-Induced Liver Injury: A Possible Strategy of Chikusetsusaponin V Targeting NETs Formation
In this study, APAP stimulation increased the level of HMGB1, IL-1β and Caspase-1 in mouse liver, especially hepatocytes, which had a synergistic effect with LPS/ATP combination. NETs were formatted at early stage of APAP or HMGB1-stimulated neutrophils’ damage. Conditioned mediums from APAP-treated hepatocytes induced more significant NETs than direct APAP stimulation. Neutrophil depletion or abolishing NETs formation decreased HMGB1 level, eventually blocked hepatocytes necrosis. CKV pretreatment interfered Caspase-1 activation and HMGB1 release in APAP-damaged hepatocytes. CKV also prevented NETs formation. T...
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Effects of Tranexamic Acid on Hemorrhage Control and Deep Venous Thrombosis Rate After Total Knee Arthroplasty: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Conclusions: TXA therapies in this study are effective and safe for the treatment of TKA-induced complications. M therapy (IV/IV infusion + oral TXA> 3 g) may be the most effective TXA therapy for hemorrhage control. TXA therapies in this study do not increase DVT risk. Considering hemorrhage control and DVT rate simultaneously, F therapy (IV TXA ≥ 15 mg/kg or 1 g three times) may be suggested to apply for TKA, and this study may provide a crucial clue to future TXA use. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage
To investigate the neuroprotective effect of brimonidine after retinal ischemia damage on mouse eye. Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGCs) death, irreversible peripheral and central visual field loss, and high intraocular pressure. Ischemia reperfusion (I/R) injury model was used in C57BL/6J mice to mimic conditions of glaucomatous neurodegeneration. Mouse eyes were treated topically with brimonidine and pattern electroretinogram were used to assess the retinal ganglion cells (RGCs) function. A wide range of inflammatory markers, as well as anti-inflammatory and neurotrophic molecul...
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Switching and Discontinuation Pattern of Biologic Disease-Modifying Antirheumatic Drugs and Tofacitinib for Patients With Rheumatoid Arthritis in Taiwan
In conclusion, this population-based study found that TNFi were the preferred agents as the index treatments during 2012–2017. Non-TNFi and tofacitinib were more common second-line agents being switched to. Nearly half of discontinued patients received retreatment, with a majority receiving the same agent. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Bicyclol Alleviates Signs of BDL-Induced Cholestasis by Regulating Bile Acids and Autophagy-Mediated HMGB1/p62/Nrf2 Pathway
In this study, we investigated the protective effect of bicyclol in cholestasis caused by bile duct ligation (BDL), as well as relevant mechanisms. Bicyclol attenuated liver damage in BDL mice by increasing the levels of hydrophilic bile acid such as α-MCA and β-MCA, regulating bile acid-related pathways and improving histopathological indexes. High-mobility group box 1 (HMGB1) is an extracellular damage-associated molecular pattern molecule which can be used as biomarkers of cells and host defense. Bicyclol treatment decreased extracellular release of HMGB1. In addition, HMGB1 is also involved in regulating aut...
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Three-Drug Regimens Containing Integrase Inhibitor Show Good Efficacy and Safety in Treatment-Naive Patients With HIV-1: A Bayesian Analysis
Conclusion: 3-drug regimens containing INI demonstrate better efficacy and safety than those containing RPV or EFV. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Exploring Phytochemicals for Combating Antibiotic Resistance in Microbial Pathogens
Antibiotic resistance or microbial drug resistance is emerging as a serious threat to human healthcare globally, and the multidrug-resistant (MDR) strains are imposing major hurdles to the progression of drug discovery programs. Newer antibiotic-resistance mechanisms in microbes contribute to the inefficacy of the existing drugs along with the prolonged illness and escalating expenditures. The injudicious usage of the conventional and commonly available antibiotics in human health, hygiene, veterinary and agricultural practices is proving to be a major driver for evolution, persistence and spread of antibiotic-resistance a...
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Glycoproteins From Rabdosia japonica var. glaucocalyx Regulate Macrophage Polarization and Alleviate Lipopolysaccharide-Induced Acute Lung Injury in Mice via TLR4/NF- κB Pathway
Conclusion: XPS was demonstrated to be a potential agent for treating ALI. Our findings might provide evidence supporting the traditional application of R. japonica var. glaucocalyx in inflammation-linked diseases. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Cardiovascular Toxicity Induced by Chronic Vincristine Treatment
In conclusion, chronic treatment with vincristine causes functional alterations in the vascular function of both conductance and resistance vessels and changes in the expressions of TNFα, eNOS, iNOS, and connexin 43 in cardiovascular tissues, implicating direct toxicity during its treatment. These functional alterations are transitory and disappear after the suspension of its treatment. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Crosstalk Between Dysfunctional Mitochondria and Inflammation in Glaucomatous Neurodegeneration
Mitochondrial dysfunction and excessive inflammatory responses are both sufficient to induce pathology in age-dependent neurodegenerations. However, emerging evidence indicates crosstalk between damaged mitochondrial and inflammatory signaling can exacerbate issues in chronic neurodegenerations. This review discusses evidence for the interaction between mitochondrial damage and inflammation, with a focus on glaucomatous neurodegeneration, and proposes that positive feedback resulting from this crosstalk drives pathology. Mitochondrial dysfunction exacerbates inflammatory signaling in multiple ways. Damaged mitochondrial DN...
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Biomarkers for the Clinical Diagnosis of Alzheimer ’s Disease: Metabolomics Analysis of Brain Tissue and Blood
With an increase in aging populations worldwide, age-related diseases such as Alzheimer’s disease (AD) have become a global concern. At present, a cure for neurodegenerative disease is lacking. There is an urgent need for a biomarker that can facilitate the diagnosis, classification, prognosis, and treatment response of AD. The recent emergence of highly sensitive mass-spectrometry platforms and high-throughput technology can be employed to discover and catalog vast datasets of small metabolites, which respond to changed status in the body. Metabolomics analysis provides hope for a better understanding of AD as well ...
Source: Frontiers in Pharmacology - July 21, 2021 Category: Drugs & Pharmacology Source Type: research

Corrigendum: Therapeutic Potentials of Antiviral Plants Used in Traditional African Medicine With COVID-19 in Focus: A Nigerian Perspective
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacotherapy for Beh çet’s Disease and the Risk of Malignancy
Conclusion: Our study revealed that CYC was associated with a high risk of cancer in BD patients. Furthermore, C4 and Hb are independent protective factors for oncogenesis in BD patients. These findings may provide references and suggestions for clinicians to select appropriate treatments and for the early recognition of high-risk patients to reduce cancer incidence in BD patients. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research

Physiologically Based Pharmacokinetic Modelling for Nicotine and Cotinine Clearance in Pregnant Women
Conclusion: The proposed p-PBPK model produces results consistent with available data sources. Further pharmacokinetic experiments are required to calibrate clearance parameters for individual organs, and for the fetus. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research

Case Report: Predicting the Range of Lamotrigine Concentration Using Pharmacokinetic Models Based on Monte Carlo Simulation: A Case Study of Antiepileptic Drug-Related Leukopenia
We report the case of a 15-year-old Chinese female epileptic patient weighing 60 kg who developed combined asymptomatic leukopenia after receiving concomitant therapy with LTG and valproate acid (VPA). In this case report, antiepileptic drug-related leukopenia may have occurred in definite relation to an increase in LTG concentration and reversed with the discontinuation of VPA. Monte Carlo (MC) simulations were performed to estimate the steady-state serum concentrations (Css) of LTG for different dosing regimens in adolescent Chinese epileptic patients weighing the same as the patient considered in the case study, ba...
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research

The Role of Co-Signaling Molecules in Psoriasis and Their Implications for Targeted Treatment
Psoriasis is a chronic, systemic immune-mediated inflammatory disease manifesting in the skin, joint or both. Co-signaling molecules are essential for determining the magnitude of the T cell response to the antigen. According to the function of co-signaling molecules, they can be divided into co-stimulatory molecules and co-inhibitory molecules. The role of co-signaling molecules in psoriasis is recognized, mainly including the co-stimulatory molecules CD28, CD40, OX40, CD27, DR3, LFA-1, and LFA-3 and the co-inhibitory molecules CTLA-4, PD-1, and TIM-3. They impact the pathological process of psoriasis by modulating the im...
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research

The Role of Gasotransmitters in Gut Peptide Actions
Although gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) receive a bad connotation; in low concentrations these play a major governing role in local and systemic blood flow, stomach acid release, smooth muscles relaxations, anti-inflammatory behavior, protective effect and more. Many of these physiological processes are upstream regulated by gut peptides, for instance gastrin, cholecystokinin, secretin, motilin, ghrelin, glucagon-like peptide 1 and 2. The relationship between gasotransmitters and gut hormones is poorly understood. In this review, we discuss the role of NO, CO and H2S on ...
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research

Remimazolam: Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent
A program to identify novel intravenous sedatives with a short and predictable duration of action was initiated in the late 1990’s by Glaxo Wellcome. The program focussed on the identification of ester-based benzodiazepine derivatives that are rapidly broken down by esterases. Remimazolam was identified as one of the lead compounds. The project at Glaxo was shelved for strategic reasons at the late lead optimization stage. Via the GSK ventures initiative, the program was acquired by the small biotechnology company, TheraSci, and, through successive acquisitions, developed as the besylate salt at CeNeS and PAION. The ...
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research

Patient Preferences for Attributes of Chemotherapy for Lung Cancer: Discrete Choice Experiment Study in Japan
Our study objective was to determine lung cancer chemotherapy attributes that are important to patients in Japan. A discrete choice experiment survey in an anonymous web-based questionnaire format with a reward was completed by 200 lung cancer patients in Japan from November 25, 2019, to November 27, 2019. The relative importance of patient preferences for each attribute was estimated using a conditional logit model. A hierarchical Bayesian logit model was also used to estimate the impact of each demographic characteristic on the relative importance of each attribute. Of the 200 respondents, 191 with consistent responses w...
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research

Medicinal Plants Used for Treating Mild Covid-19 Symptoms Among Thai Karen and Hmong
Conclusion: This study suggests alternative treatments for mild symptoms of COVID-19 with medicinal plants that are traditionally used by the ethnic minority groups of the Hmong and Karen in Thailand. Although COVID-19 is a new disease, its mild symptoms are shared with many other diseases. Traditional knowledge on medicinal plants used by the Thai Karen and Hmong could help in the treatments of these symptoms associated with COVID-19. Many of the proposed plants were used abundantly by both ethnic groups, and other studies on biological activities support their efficacy in such treatments. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research

Antileishmanial Activity of Flavones-Rich Fraction From Arrabidaea chica Verlot (Bignoniaceae)
Acknowledging the need of identifying new compounds for the treatment of leishmaniasis, this study aimed to evaluate, from in vitro trials, the activity of flavones from Arrabidaea chica against L. amazonensis. The chromatographic profiles of the hydroethanolic extract and a flavone-rich fraction (ACFF) from A. chica were determined by high-performance liquid chromatography coupled with a diode-array UV-Vis detector (HPLC-DAD-UV) and electrospray ionization mass spectrometry in tandem (LC-ESI-MS-MS). The flavones luteolin (1) and apigenin (2), isolated from chromatographic techniques and identified by Nuclear Magnetic Reso...
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research

Diarylpentanoid (1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one) (MS13) Exhibits Anti-proliferative, Apoptosis Induction and Anti-migration Properties on Androgen-independent Human Prostate Cancer by Targeting Cell Cycle –Apoptosis and PI3K Signalling Pathways
Diarylpentanoids exhibit a high degree of anti-cancer activity and stability in vitro over curcumin in prostate cancer cells. Hence, this study aims to investigate the effects of a diarylpentanoid, 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13) on cytotoxicity, anti-proliferative, apoptosis-inducing, anti-migration properties, and the underlying molecular mechanisms on treated androgen-independent prostate cancer cells, DU 145 and PC-3. A cell viability assay has shown greater cytotoxicity effects of MS13-treated DU 145 cells (EC50 7.57 ± 0.2 µM) and PC-3 cells (EC50 7.80 ± 0.7 ...
Source: Frontiers in Pharmacology - July 20, 2021 Category: Drugs & Pharmacology Source Type: research