Glycyrrhizic Acid Promotes Osteogenic Differentiation of Human Bone Marrow Stromal Cells by Activating the Wnt/ β-Catenin Signaling Pathway
Glycyrrhizic acid (GA) is a major triterpene glycoside isolated from liquorice root that has been shown to inhibit osteoclastogenesis. However, there have been no reports regarding the effect of GA on osteogenic differentiation. Therefore, this study was performed to explore the effects and mechanism of action of GA on osteogenesis. A CCK-8 array was used to assess cell viability. The osteogenic capability was investigated by real-time quantitative PCR, western blotting and immunofluorescence analyses. ALP staining and ARS were used to evaluate ALP activity and mineralization, respectively. GA-GelMA hydrogels were designed...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Targeted Therapy in Cardiovascular Disease: A Precision Therapy Era
Targeted therapy refers to exploiting the specific therapeutic drugs against the pathogenic molecules (a protein or a gene) or cells. The drug specifically binds to disease-causing molecules or cells without affecting normal tissue, thus enabling personalized and precision treatment. Initially, therapeutic drugs included antibodies and small molecules, (e.g. nucleic acid drugs). With the advancement of the biology technology and immunotherapy, the gene editing and cell editing techniques are utilized for the disease treatment. Currently, targeted therapies applied to treat cardiovascular diseases (CVDs) mainly include prot...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Adenosine Metabotropic Receptors in Chronic Pain Management
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Leonurine-Repressed miR-18a-5p/SOCS5/JAK2/STAT3 Axis Activity Disrupts CML malignancy
Leonurine, an active natural alkaloid compound isolated from Herba leonuri, has been reported to exhibit promising anticancer activity in solid tumors. The aim of this study was to explore whether leonurine is able to inhibit chronic myeloid leukemia (CML) malignancy. Here, we found that leonurine dose dependently inhibited the proliferation, migration, colony formation and promoted apoptosis of CML cells. Furthermore, leonurine markedly reduced CML xenograft growth in vivo. Mechanically, leonurine upregulated SOCS5 expression, thus leading JAK2/STAT3 signaling suppression. Silencing of SOCS5 by its siRNA abrogated the eff...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

SLE-DAS in the First Trimester of Gestation Predicts Maternal Lupus Flares Later in Pregnancy
Introduction: Systemic Lupus Erythematosus (SLE) mainly occurs during childbearing age. Remission or low disease activity state (LDAS) before conception are recommended by experts to achieve a favourable lupus pregnancy outcome but little is known on the best way to evaluate remission or activity status during pregnancy.Objectives: We tested SLE-disease activity score (SLE-DAS) in the first trimester as predictor of maternal flares and obstetrical complications in 2nd and 3rd trimester in a cohort of SLE pregnant women.Patients and Methods: Inclusion criteria were: 1) women ≥ 18 years; 2) affected with SLE (SLICC 2...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Clozapine Metabolism is Associated With Absolute Neutrophil Count in Individuals With Treatment-Resistant Schizophrenia
Up to one-third of those with schizophrenia fail to respond to standard antipsychotics and are considered to have treatment-resistant schizophrenia, a condition for which clozapine is the only evidence-based medication. While up to 60% of treated individuals obtain therapeutic benefits from clozapine, it is currently underprescribed worldwide, partly because of concerns related to its broad adverse effect profile. In particular, the potential effects of clozapine on the immune system have gained relevance after a recent study showed that drug plasma concentrations were inversely correlated with neutrophil counts in individ...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Dose-Related Urinary Metabolic Alterations of a Combination of Quercetin and Resveratrol-Treated High-Fat Diet Fed Rats
Most herbal polyphenols and flavonoids reveals multiple ameliorative benefits for obesity caused by chronic metabolic disorders. Accumulated studies have revealed that preferable therapeutic effects can be obtained through clinical combination of these two kinds of natural compounds for obesity improvement. The typical representative research was the combination of quercetin and resveratrol (CQR), in which the ratio of quercetin and resveratrol is 2:1, demonstrating a synergistic effect in anti-obesity process. Although there exists reports clarifying the mechanism of the combination of two to improve obesity from the pers...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Case Report: The Complexities of Managing Medications and the Importance of Deprescribing Anticholinergics in Older Adults
We present the case of a frail 86-year old female from the perspective of a community pharmacist managing outpatient medications and transitions of care. CD’s past medical history is significant for dementia, multiple falls, recurrent urinary tract infections, depression, cardiac arrhythmia, macular degeneration, chronic pain, depression, and cerebrovascular disease. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Unfolding New Roles for Guanine-Based Purines and Their Metabolizing Enzymes in Cancer and Aging Disorders
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Chemopreventive and Anticancer Property of Selenoproteins in Obese Breast Cancer
Obesity is a significant risk factor for various cancers including breast cancer resulting in an increased risk of recurrence as well as morbidity and mortality. Extensive studies on various pathways have been successful in establishing a biological relationship between obesity and breast cancer. The molecular classification of breast cancer includes five groups each having different responses to treatment. Increased levels of inflammatory cytokines seen in obese conditions drive the pro-proliferative pathways, such as the influx of macrophages, angiogenesis, and antiapoptotic pathways. Increased peripheral aromatization o...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Improved Survival and Retinal Function of Aging ZDF Rats in Long-Term, Uncontrolled Diabetes by BGP-15 Treatment
Retinal complications of diabetes often lead to deterioration or even loss of vision. This hastens discovery of pharmacological agents able to counterbalance diabetic retinopathy. BGP-15, an emerging small molecule agent, was formerly proven by our workgroup to be retinoprotective on nonobese diabetic animals, Goto-Kakizaki rats. In the present study, we aimed to examine its long-term tolerability or incidental side effects on obese-prone Zucker diabetic fatty (ZDF) rats to further increase the rationale for a future human translation. To make terminal visual status comparable with our other investigations, we also carried...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Editorial: Novel Cancer Treatments Based on Autophagy Modulation
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

MicroRNA-223 Suppresses IL-1 β and TNF-α Production in Gouty Inflammation by Targeting the NLRP3 Inflammasome
Introduction: MicroRNA-223 (MiR-223) serves as an important regulator of inflammatory and immune responses and is implicated in several auto-inflammatory disorders. Here, we measured miR-223 expression in acute and intercritical gout patients, after which we used RAW264.7 macrophages transfected with a miR-223 mimic/inhibitor to determine the function of miR-223 in monosodium urate (MSU)-induced gouty inflammation.Methods and Results: MiR-223 was detected among 122 acute gout patients (AG), 118 intercritical gout patients (IG), and 125 healthy subjects (HC). RAW264.7 macrophages were cultured and treated with MSU. Over-exp...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

The Effects of Repeated Morphine Treatment on the Endogenous Cannabinoid System in the Ventral Tegmental Area
The therapeutic utility of opioids is diminished by their ability to induce rewarding behaviors that may lead to opioid use disorder. Recently, the endogenous cannabinoid system has emerged as a hot topic in the study of opioid reward but relatively little is known about how repeated opioid exposure may affect the endogenous cannabinoid system in the mesolimbic reward circuitry. In the present study, we investigated how sustained morphine may modulate the endogenous cannabinoid system in the ventral tegmental area (VTA) of Sprague Dawley rats, a critical region in the mesolimbic reward circuitry. Studies here using proteom...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Improved Treatment Outcomes by Using Patient Specific Drug Combinations in Mammalian Target of Rapamycin Activated Advanced Metastatic Cancers
Conclusion: Patient-specific combination regimens with mTOR inhibition and other anti-neoplastic agents, when selected based on multi-analyte molecular and functional profiling of the tumor can yield meaningful outcomes in advanced or refractory solid organ cancers.Trial Registration: Details of all trials are available at WHO-ICTRP: https://apps.who.int/trialsearch/. RESILIENT ID CTRI/2018/02/011808. ACTPRO ID CTRI/2018/05/014178. LIQUID IMPACT ID CTRI/2019/02/017548. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

IMCC: A Novel Quantitative Approach Revealing Variation of Global Modular Map and Local Inter-Module Coordination Among Differential Drug ’s Targeted Cerebral Ischemic Networks
Stroke is a common disease characterized by multiple genetic dysfunctions. In this complex disease, detecting the strength of inter-module coordination (genetic community interaction) and subsequent modular rewiring is essential to characterize the reactive biosystematic variation (biosystematic perturbation) brought by multiple-target drugs, whose effects are achieved by hitting on a series of targets (target profile) jointly. Here, a quantitative approach for inter-module coordination and its transition, named as IMCC, was developed. Applying IMCC to mouse cerebral ischemia–related gene microarray, we investigated ...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Corrigendum: Predicting the Effects of CYP2C19 and Carboxylesterases on Vicagrel, a Novel P2Y12 Antagonist, by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Approach
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Corrigendum: Composition and Functionality of Lipid Emulsions in Parenteral Nutrition: Examining Evidence in Clinical Applications
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Atorvastatin Upregulates microRNA-186 and Inhibits the TLR4-Mediated MAPKs/NF- κB Pathway to Relieve Steroid-Induced Avascular Necrosis of the Femoral Head
In conclusion, Ato reduced apoptosis and promoted autophagy, thus alleviating SANFH via miR-186 and the TLR4-mediated MAPKs/NF-κB pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

Role of Leptin in the Digestive System
Leptin is a pluripotent peptide hormone produced mainly by adipocytes, as well as by other tissues such as the stomach. Leptin primarily acts on the central nervous system, particularly the hypothalamus, where this hormone regulates energy homeostasis and neuroendocrine function. Owing to this, disruption of leptin signaling has been linked with numerous pathological conditions. Recent studies have also highlighted the diverse roles of leptin in the digestive system including immune regulation, cell proliferation, tissue healing, and glucose metabolism. Of note, leptin acts differently under physiological and pathological ...
Source: Frontiers in Pharmacology - April 16, 2021 Category: Drugs & Pharmacology Source Type: research

PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer ’s Disease and Parkinson’s Disease
This article reviews the relationship between AKT signaling pathway and AD and PD, and discusses the potential natural products based on the PI3K/AKT signaling pathway to treat two diseases in recent years, hoping to provide guidance and reference for this field. Further development of Chinese herbal medicine is needed to treat these two diseases. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Multifocal Analysis of Acute Pain After Third Molar Removal
Conclusion: Polymorphisms in COMT, salivary concentrations of IL-2 and IFN-γ, BMI, and duration of surgery were predictors for pain fluctuation, swelling, and trismus on the 2nd day after lower third molar extraction. This therapy was effective in controlling inflammatory symptomatology after lower third molar extraction and ibuprofen was well tolerated by patients.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03169127. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Effect of Different Ratios of Yinchen and Gancao Decoction on ANIT-Treated Cholestatic Liver Injury in Mice and Its Potential Underlying Mechanism
Cholestasis is a pathological state that leads to serious liver disease; however, therapeutic options remain limited. Yinchen and Gancao are often used in combination at different ratios in traditional Chinese formulae for the treatment of jaundice and cholestasis. In the present study, we investigated the effect of decoctions containing different ratios of Yinchen and Gancao (YGD) on alpha-naphthyl isothiocyanate (ANIT)-treated intrahepatic cholestasis (IC) in mice, and further explored the underlying mechanism. Treatment with 0:4 and 1:4 YGD significantly reduced plasma total bile acid (TBA), total bilirubin (TBIL), aspa...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Probiotic Lactobacilli Isolated from Kefir Promote Down-Regulation of Inflammatory Lamina Propria T Cells from Patients with Active IBD
Ulcerative colitis and Crohn’s disease, the two main forms of inflammatory bowel disease (IBD), are immunologically mediated disorders. Several therapies are focused on activated T cells as key targets. Although Lactobacillus kefiri has shown anti-inflammatory effects in animal models, few studies were done using human mucosal T cells. The aim of this work was to investigate the immunomodulatory effects of this bacterium on intestinal T cells from patients with active IBD. Mucosal biopsies and surgical samples from IBD adult patients (n = 19) or healthy donors (HC; n = 5) were used. Lamina propria mononuclear cells w...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Comparison of Rifamycins for Efficacy Against Mycobacterium avium Complex and Resistance Emergence in the Hollow Fiber Model System
The objective of the study was to compare microbial kill and resistance emergence of rifamycins using principles of pharmacokinetics/pharmacodynamics. First, we identified rifamycin MICs in 20 MAC isolates from patients followed by concentration-response studies in test-tubes. Next, we examined efficacy and resistance suppression of three doses of each rifamycin in the hollow fiber system model of pulmonary MAC [HFS-MAC], mimicking human like concentration-time profile of the drugs. HFS-MAC units were repetitively sampled for total and drug-resistant MAC burden and for drug concentration measurements. Inhibitory sigmoid E ...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Xiaoyao Pills Ameliorate Depression-like Behaviors and Oxidative Stress Induced by Olfactory Bulbectomy in Rats via the Activation of the PIK3CA-AKT1-NFE2L2/BDNF Signaling Pathway
The objective of our study was to investigate the antidepressant-like effects of XYW and the underlying molecular mechanism in the olfactory bulbectomized (OB) rat model of depression using the open field test (OFT), sucrose preference test (SPT), splash test (ST), and novelty suppressed feeding test (NSFT). Results showed that XYW (0.93 and 1.86 g·kg−1) significantly alleviated depression-like behaviors in rats, which was indicated by increased sucrose preference in the SPT, prolonged grooming time in the ST, decreased horizontal movement in the OFT, and shorter feeding latency in the NSFT. In addition, ...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Hepatic Cytochrome P450 Abundance and Activity in the Developing and Adult G öttingen Minipig: Pivotal Data for PBPK Modeling
The Göttingen Minipig is gaining ground as nonrodent species in safety testing of drugs for pediatric indications. Due to developmental changes in pharmacokinetics and pharmacodynamics, physiologically based pharmacokinetic (PBPK) models are built to better predict drug exposure in children and to aid species selection for nonclinical safety studies. These PBPK models require high quality physiological and ADME data such as protein abundance of drug metabolizing enzymes. These data are available for man and rat, but scarce for the Göttingen Minipig. The aim of this study was to assess hepatic cytochrome P450 (CYP...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

E3 Ubiquitin Ligase in Anticancer Drugdsla Resistance: Recent Advances and Future Potential
Drug therapy is the primary treatment for patients with advanced cancer. The use of anticancer drugs will inevitably lead to drug resistance, which manifests as tumor recurrence. Overcoming chemoresistance may enable cancer patients to have better therapeutic effects. However, the mechanisms underlying drug resistance are poorly understood. E3 ubiquitin ligases (E3s) are a large class of proteins, and there are over 800 putative functional E3s. E3s play a crucial role in substrate recognition and catalyze the final step of ubiquitin transfer to specific substrate proteins. The diversity of the set of substrates contributes...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Different Pharmacokinetics of Tramadol, O-Demethyltramadol and N-Demethyltramadol in Postoperative Surgical Patients From Those Observed in Medical Patients
Conclusions:CYP2D6 polymorphism is a major factor in O-demethylation, while systemic inflammation accompanied by low ChE has an important role in the N-demethylation of tramadol in postoperative patients. Concentrations of tramadol, ODT, and NDT are lower in surgical patients than previously reported in non-surgical patients.Clinical Trial Registration: ClinicalTrials.gov, NCT04004481. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Ficus erecta Thunb. Leaves Ameliorate Cognitive Deficit and Neuronal Damage in a Mouse Model of Amyloid- β-Induced Alzheimer’s Disease
Alzheimer’s disease (AD) pathogenesis is linked to amyloid plaque accumulation, neuronal loss, and brain inflammation. Ficus erecta Thunb. is a food and medicinal plant used to treat inflammatory diseases. Here, we investigated the neuroprotective effects of F. erecta Thunb. against cognitive deficit and neuronal damage in a mouse model of amyloid-β (Aβ)-induced AD. First, we confirmed the inhibitory effects of ethanol extracts of F. erecta (EEFE) leaves on Aβ aggregation in vivo and in vitro. Next, behavioral tests (passive avoidance task and Morris water maze test) revealed EEFE markedly improved cog...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Bridging the Translational Divide in Pain Research: Biological, Psychological and Social Considerations
A gap exists between translating basic science research into effective pain therapies in humans. While preclinical pain research has primarily used animal models to understand biological processes, a lesser focus has been toward using animal models to fully consider other components of the pain experience, such as psychological and social influences. Herein, we provide an overview of translational studies within pain research by breaking them down into purely biological, psychological and social influences using a framework derived from the biopsychosocial model. We draw from a wide landscape of studies to illustrate that ...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Inflammation Pharmacological Reaction and YMDD Mutational Patterns in Lamivudine Therapeutics Hepatitis B Virus
Conclusions: Illuminating inflammation pharmacological reaction and YMDD mutational patterns of CHB during pathological process may have implications for future therapy in YMDD mutation patients. This may have impact on the choice of treatment strategies for lamivudine-resistant HBV. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Resveratrol Prevents Campylobacter jejuni-Induced Leaky gut by Restoring Occludin and Claudin-5 in the Paracellular Leak Pathway
In conclusion, the induction of the leak pathway by C. jejuni and the restoration of barrier function by resveratrol demonstrates its effectiveness as a potential preventive or therapeutic method of mitigating the leaky gut associated with campylobacteriosis. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

A Review of the Toxicity and Phytochemistry of Medicinal Plant Species Used by Herbalists in Treating People Living With HIV/AIDS in Uganda
Conclusion: Cytotoxicity varied with cell type, solvent and extract type used making it difficult for direct comparison of the plant species. Five of the eleven plant species namely, A. coriaria, C. sanguinolenta, G. ternifolia, P. febrifugium and Z. chalybeum had no cytotoxicity studies in animal models. For the remaining six plant species, the crude aqueous and ethanol extracts were mainly used in acute oral toxicity studies in mice. Herbalists reported only A. coriaria and W. ugandensis to cause toxic side effects in humans. However, selective cytotoxic plant extracts can potentially be beneficial as anticancer or anti-...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Th17 Cells in Depression: Are They Crucial for the Antidepressant Effect of Ketamine?
Conclusion: As Th17 cells play multiple roles in depression, it is important to explore the mechanisms of action of ketamine on Th17 cells and Th17/Treg cell balance. This provides new perspectives for strengthening the antidepressant effect of ketamine while reducing its side effects and adverse reactions. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Transcriptomic and microRNA Expression Profiles Identify Biomarkers for Predicting Neo-Chemoradiotherapy Response in Esophageal Squamous Cell Carcinomas (ESCC)
This study aimed to identify potential biomarkers for prediction of nCRT-response in patients with esophageal squamous cell carcinoma (ESCC). Microarray datasets of nCRT responder and non-responder samples (access number GSE45670 and GSE59974) of patients with ESCC were downloaded from Gene Expression Omnibus (GEO) database. The mRNA expression profiles of cancer biopsies from four ESCC patients were analyzed before and after nCRT. Differentially expressed genes (DEGs) and miRNAs were screened between nCRT responder and non-responder ESCC samples. Functional enrichment analysis was conducted for these DEGs followed by cons...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics of Anthraquinones from Medicinal Plants
Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce p...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Cardioprotective Roles of β-Hydroxybutyrate Against Doxorubicin Induced Cardiotoxicity
Conclusion: Our results suggested that BHB could protected from DOX-induced cardiotoxicity by inhibiting cell apoptosis and oxidative stress and maintaining mitochondrial membrane integrity. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Na + , K + ATPase as a target of cardiac glycosides for the treatment of SARS-Cov-2 infection
The new coronavirus (SARS-CoV-2), identified the first time in Wuhan, China, overcame epidemic status becoming pandemic. Since its discovery in December 2019, there were countless cases of mortality and morbidity. Several compounds such as chloroquine, hydroxychloroquine, liponavir-ritonavir, and remdesivir have been tested as alternative therapy; however, no effective treatment is recommended by regulatory agencies. Some studies on respiratory non-enveloped viruses such as adenoviruses and rhinovirus and some respiratory enveloped viruses, including human respiratory syncytial viruses, influenza A, parainfluenza, SARS-CoV...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

New Trends in Pharmacological Treatments for Osteoarthritis
Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease...
Source: Frontiers in Pharmacology - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Community-Based Interventions to Improve the Control of Non-Communicable Diseases in Underserved Rural Areas in Brazil: A Before-and-After Study
Background: Hypertension and diabetes mellitus are the second and third highest leading causes of disability-adjusted life-years (DALY), respectively, in Brazil. The clinical outcomes of chronic diseases are influenced by various factors. Therefore, there is a need for multifaceted interventions to achieve a decrease in the rate of DALY, with a better control of these diseases.Objective: To verify whether sustainable long-term interventions, such as health worker training and provision of health education to the patients, contribute to health improvements in patients with hypertension and diabetes from rural communities.Me...
Source: Frontiers in Pharmacology - April 14, 2021 Category: Drugs & Pharmacology Source Type: research

Organic Cation Transporter 1 an Intestinal Uptake Transporter: Fact or Fiction?
Intestinal transporter proteins are known to affect the pharmacokinetics and in turn the efficacy and safety of many orally administered drugs in a clinically relevant manner. This knowledge is especially well-established for intestinal ATP-binding cassette transporters such as P-gp and BCRP. In contrast to this, information about intestinal uptake carriers is much more limited although many hydrophilic or ionic drugs are not expected to undergo passive diffusion but probably require specific uptake transporters. A transporter which is controversially discussed with respect to its expression, localization and function in t...
Source: Frontiers in Pharmacology - April 14, 2021 Category: Drugs & Pharmacology Source Type: research

Cost-Effectiveness of Alirocumab for the Secondary Prevention of Cardiovascular Events after Myocardial Infarction in the Chinese Setting
Conclusion: Alirocumab is not cost-effective in general MI population based on current discounted price. High long-term costs of alirocumab may be offset by health benefit in patients with polyvascular disease (3 beds). (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 14, 2021 Category: Drugs & Pharmacology Source Type: research

Efficacy and Safety of Denosumab in Osteoporosis or Low Bone Mineral Density Postmenopausal Women
This study aimed to update the efficacy and safety of denosumab vs. placebo in osteoporosis or low bone mineral density (BMD) postmenopausal women. PubMed, Embase, Cochrane library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) reporting the efficacy and safety data of denosumab vs. placebo in osteoporosis or low BMD postmenopausal women. A random-effects model was used to calculate pooled weight mean differences (WMDs) or relative risks (RRs) with corresponding 95% confidence intervals (CIs) for treatment effectiveness of denosumab vs. placebo. Eleven RCTs including 12,013 postmenopausal wom...
Source: Frontiers in Pharmacology - April 14, 2021 Category: Drugs & Pharmacology Source Type: research

Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy
In conclusion, the study identified potential and novel biomarkers for POAG by crosslinking the metabolomic profiles in aqueous humor and plasma and correlating with the clinical parameters. These findings have important clinical implications given that no biomarkers are currently available for glaucoma in the clinic, and the study provided new insights in exploring diagnostic biomarkers and potential therapeutic strategies of POAG by targeting metabolic pathways. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 14, 2021 Category: Drugs & Pharmacology Source Type: research

Neutrophil Elastase Induces Chondrocyte Apoptosis and Facilitates the Occurrence of Osteoarthritis via Caspase Signaling Pathway
Osteoarthritis (OA) is the most common and prevalent chronic joint disorders in the elderly population across the globe, resulting in severe disability and impairment of quality of life. Existing treatment can only alleviate the symptoms and delay the progression of OA. Therefore, novel and effective therapeutics strategies for OA need to be developed. Our present study first found that neutrophil elastase (NE) was significantly increased in OA patients’ synovial fluid. Next, we examined the effect of neutrophil elastase (NE) on chondrocytes in vitro and in vivo. The results showed that NE suppressed cell proliferati...
Source: Frontiers in Pharmacology - April 14, 2021 Category: Drugs & Pharmacology Source Type: research

Development and Validation of an Interleukin-6 Nomogram to Predict Primary Non-response to Infliximab in Crohn ’s Disease Patients
Background: The primary non-response (PNR) rate of infliximab (IFX) varies from 20 to 46% for the treatment of Crohn’s disease (CD). Detected PNR reduces the improper use of specific treatments. To date, there is hardly any knowledge regarding early markers of PNR. The aim of this study was to evaluate the role of Interleukin-6 (IL-6) as an early predictor of PNR of IFX for the treatment of CD.Methods: We enrolled 322 bio-naïve patients diagnosed with CD from January 2016 to May 2020. Primary response was determined at week 14. Multivariable logistic regression was used to construct prediction models. Area under...
Source: Frontiers in Pharmacology - April 14, 2021 Category: Drugs & Pharmacology Source Type: research

Jianpi Jieyu Decoction, An Empirical Herbal Formula, Exerts Psychotropic Effects in Association With Modulation of Gut Microbial Diversity and GABA Activity
Conclusion: JPJY regulates gut microbiota to produce antidepressant-like effect and improve cognition deficit in depressive mice while its molecular mechanism possibly be enhanced NR1 and Tau expression in hippocampus and increased GABA in serum. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - April 14, 2021 Category: Drugs & Pharmacology Source Type: research

Natural Polysaccharides and Their Derivates: A Promising Natural Adjuvant for Tumor Immunotherapy
The treatment process of tumor is advanced with the development of immunotherapy. In clinical experience, immunotherapy has achieved very significant results. However, the application of immunotherapy is limited by a variety of immune microenvironment. For a long time in the past, polysaccharides such as lentinan and Ganoderma lucidum glycopeptide have been used in clinic as adjuvant drugs to widely improve the immunity of the body. However, their mechanism in tumor immunotherapy has not been deeply discussed. Studies have shown that natural polysaccharides can stimulate innate immunity by activating upstream immune cells ...
Source: Frontiers in Pharmacology - April 14, 2021 Category: Drugs & Pharmacology Source Type: research

Detection of EGFR Mutations From Plasma of NSCLC Patients Using an Automatic Cartridge-Based PCR System
The introduction of liquid biopsies for the detection of EGFR mutations in non-small cell lung cancer patients (NSCLC) has revolutionized the clinical care. However, liquid biopsies are technically challenging and require specifically trained personnel. To facilitate the implementation of liquid biopsies for the detection of EGFR mutations from plasma, we have assessed a fully automated cartridge-based qPCR test that allows the automatic detection of EGFR mutations directly from plasma. We have analyzed 54 NSCLC patients and compared the results of the cartridge-base device to an FDA-approved assay. Detection of EGFR mutat...
Source: Frontiers in Pharmacology - April 14, 2021 Category: Drugs & Pharmacology Source Type: research