Big Data and Real-World Data based Cost-Effectiveness Studies and Decision-making Models: A Systematic Review and Analysis
Conclusion: The review shows that RWD has been increasingly applied in conducting the cost-effectiveness analysis. However, few CEA studies are based on big data. In future CEA studies using big data and RWD, it is encouraged to control confounders and to discount in long-term research when decision-analytic models are not used. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Klotho as Potential Autophagy Regulator and Therapeutic Target
The protein Klotho can significantly delay aging, so it has attracted widespread attention. Abnormal downregulation of Klotho has been detected in several aging-related diseases, such as Alzheimer’s disease, kidney injury, cancer, chronic obstructive pulmonary disease (COPD), vascular disease, muscular dystrophy and diabetes. Conversely, many exogenous and endogenous factors, several drugs, lifestyle changes and genetic manipulations were reported to exert therapeutic effects through increasing Klotho expression. In recent years, Klotho has been identified as a potential autophagy regulator. How Klotho may contribute...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation
Chemotherapy efficacy is often reduced by insufficient drug uptake in tumor cells. The combination of ultrasound and microbubbles (USMB) has been shown to improve drug delivery and to enhance the efficacy of several drugs in vitro and in vivo, through effects collectively known as sonopermeation. However, clinical translation of USMB therapy is hampered by the large variety of (non-clinical) US set-ups and US parameters that are used in these studies, which are not easily translated to clinical practice. In order to facilitate clinical translation, the aim of this study was to prove that USMB therapy using a clinical ultra...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

The Function of microRNAs in Pulmonary Embolism: Review and Research Outlook
Pulmonary embolism (PE) is a common pathologic condition that frequently occurs in patients with deep venous thrombosis. Severe PE may critically suppress cardiopulmonary function, thereby threatening the life of patients. Chronic pulmonary hypertension caused by PE may lead to deterioration of respiratory dysfunction, resulting in complete disability. MicroRNAs (miRNAs) are a group of abundantly expressed non-coding RNAs that exert multiple functions in regulating the transcriptome via post-transcriptional targeting of mRNAs. Specifically, miRNAs bind to target mRNAs in a matching mechanism between the miRNA seed sequence...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Treatment With Melatonin After Corneal Graft Attenuates Rejection
This study aimed to investigate the effect of melatonin (MT) on the rejection of corneal transplantation.Methods: Corneal allografts were performed by grafting corneas from BALB/C mice to C57BL/6 hosts. MT (50 mg/kg) was intraperitoneally injected into the hosts every day from the day of transplantation. The survival of grafts was observed by slit lamp biomicroscopy, and inflammatory cell infiltration was detected by hematoxylin and eosin staining and immunohistochemistry. The balance of Teff and Treg immune cells in draining lymph nodes (DLNs) was detected by flow cytometry. The levels of cytokines related to the gra...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Dimerized Translationally Controlled Tumor Protein-Binding Peptide 2 Attenuates Systemic Anaphylactic Reactions Through Direct Suppression of Mast Cell Degranulation
In this study, we explored the effects of dTBP2 on mast cell degranulation and allergen-induced anaphylactic reactions. We found that bacterial product lipopolysaccharide increased the expression of dTCTP in mast cells and rapidly released dTCTP by the mast cell stimulator compound 48/80. Interestingly, the released dTCTP further promoted mast cell degranulation in an autocrine activation manner and increased calcium mobilization in mast cells, which is essential for degranulation. Furthermore, dTBP2 directly and dose-dependently inhibited in vitro mast cell degranulation enhanced by compound 48/80, suggesting a direct and...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Therapeutic Potential of SphK1 Inhibitors Based on Abnormal Expression of SphK1 in Inflammatory Immune Related-Diseases
Sphingosine kinase 1(SphK1) a key enzyme that catalyzes the conversion of sphingosine (Sph) to sphingosine 1-phosphate (S1P), so as to maintain the dynamic balance of sphingolipid-rheostat in cells and participate in cell growth and death, proliferation and migration, vasoconstriction and remodeling, inflammation and metabolism. The normal expression of SphK1 maintains the balance of physiological and pathological states, which is reflected in the regulation of inflammatory factor secretion, immune response in traditional immune cells and non-traditional immune cells, and complex signal transduction. However, abnormal SphK...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Potentially Inappropriate Medications and Potential Prescribing Omissions in Elderly Patients Receiving Post-Acute and Long-Term Care: Application of Screening Tool of Older People ’s Prescriptions/Screening Tool to Alert to Right Treatment Criteria
Conclusion: PIMs and PPOs were highly prevalent in the studied patients receiving post-acute and long-term care in Units for Integrated Continuous Care. Therefore, STOPP/START criteria might be an effective tool for improving prescribing quality and clinical outcomes in these frail elderly patients. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Integrating Molecular Biomarker Inputs Into Development and Use of Clinical Cancer Therapeutics
Biomarkers can contribute to clinical cancer therapeutics at multiple points along the patient’s diagnostic and treatment course. Diagnostic biomarkers can screen or classify patients, while prognostic biomarkers predict their survival. Biomarkers can also predict treatment efficacy or toxicity and are increasingly important in development of novel cancer therapeutics. Strategies for biomarker identification have involved large-scale genomic and proteomic analyses. Pathway-specific biomarkers are already in use to assess the potential efficacy of immunotherapy and targeted cancer therapies. Judicious application of m...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Factors Associated With Off-Label Oncology Prescriptions: The Role of Cost and Financing in a Universal Healthcare System
This study characterized the financing sources of off-label oncology use and the predictors of the decision to forego treatment.Materials and Methods: All 708 off-label oncology requests submitted for approval in a large tertiary cancer center in Israel between 2016 and 2018 were examined for disease and patient sociodemographic characteristics, costs and financing sources, and the factors predicting actual off-label drug administration using multivariate logistic regression analysis.Results: The mean monthly cost of a planned off-label treatment was ILS54,703 (SD = ILS61,487, median = ILS39,928) (approximately US$ 15,500)...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis
Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, in the pathogenesis of which oxidative stress (OS) was believed to play a key role. Shenqi Fuzheng Injection (SFI) concocted from two kinds of Chinese medicinal herbs, Radix Codonopsis and Radix Astragali, was proven to be eligible to reduce the OS injury and increase the activity of the nuclear factor-erythroid-2–related factor 2 (Nrf2) pathway, an antioxidant enzymes inducer.Objective: We aim to investigate the effects and potential mechanisms underlying the action of SFI on a well-established transgenic mouse model of ALS.M...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Calycosin Alleviates Sepsis-Induced Acute Lung Injury via the Inhibition of Mitochondrial ROS-Mediated Inflammasome Activation
Sepsis-induced acute lung injury (ALI) culminates in multiple organ failure via uncontrolled inflammatory responses and requires effective treatment. Herein, we aimed to investigate the effect of calycosin (CA), a natural isoflavonoid, on sepsis-induced ALI. CA attenuated lipopolysaccharide (LPS) and cecal ligation and puncture (CLP)-induced structural damage and inflammatory cell infiltration in lung tissues by histopathological analysis. CA significantly reduced lung wet/dry ratio, inflammatory cell infiltration in bronchoalveolar lavage fluid, and myeloperoxidase activity. Moreover, CA improved the survival of septic mi...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Effect of CYP3A4 Inhibitors and Inducers on Pharmacokinetics and Pharmacodynamics of Saxagliptin and Active Metabolite M2 in Humans Using Physiological-Based Pharmacokinetic Combined DPP-4 Occupancy
We aimed to develop a physiological-based pharmacokinetic and dipepidyl peptidase 4 (DPP-4) occupancy model (PBPK-DO) characterized by two simultaneous simulations to predict pharmacokinetic (PK) and pharmacodynamic changes of saxagliptin and metabolite M2 in humans when coadministered with CYP3A4 inhibitors or inducers. Ketoconazole, delavirdine, and rifampicin were selected as a CYP3A4 competitive inhibitor, a time-dependent inhibitor, and an inducer, respectively. Here, we have successfully simulated PK profiles and DPP-4 occupancy profiles of saxagliptin in humans using the PBPK-DO model. Additionally, under the circum...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Prevention of Cyclophosphamide-Induced Immunosuppression in Mice With Traditional Chinese Medicine Xuanfei Baidu Decoction
Conclusion: Our findings suggested that XFBD played a crucial role in protection against immunosuppression in CY-treated mice and could be a potential candidate for immune modification and therapy. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Network Pharmacology –Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells
Xihuang pill, an approved Chinese medicine formula (state medical permit number. Z11020073), is a commonly used adjuvant drug for cancer patients in China. Xihuang pill has a satisfactory effect in treating breast cancer in clinics, especially triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer, and finite effective therapies. However, the mechanism of Xihuang pill in treating TNBC remains unclear. The present study aims to explore the pharmacological mechanism of Xihuang pill in treating advanced TNBC. We identified the main chemical components of Xihuang pill by using HPLC-Q-TOF-MS/MS...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Natural Product-Based Studies for the Management of Castration-Resistant Prostate Cancer: Computational to Clinical Studies
Conclusion: Our analysis suggested that natural compounds exert beneficial effects due to their broad-spectrum molecular disease-associated targets. In vitro and in vivo studies revealed several bioactive compounds, including rutaecarpine, berberine, curcumin, other flavonoids, pentacyclic triterpenoids, and steroid-based phytochemicals. Molecular modeling tools, including machine and deep learning, have made the analysis more comprehensive. Preclinical and clinical studies on resveratrol, soy isoflavone, lycopene, quercetin, and gossypol have further validated the translational potential of the natural products in the man...
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Antibiotic Treatment of Pulmonary Infections: An Umbrella Review and Evidence Map
Conclusions: We cannot evaluate which antibiotic is the best choice for the treatment of pulmonary infection. Carbapenems or adjunctive inhaled antibiotics showed a reasonable choice for HAP or VAP. However, we do not find a statistical difference between most antimicrobial therapy strategies for CAP patients. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Kaempferia galanga L.: Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses
In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 19, 2021 Category: Drugs & Pharmacology Source Type: research

Serum Amyloid A Correlates With the Osteonecrosis of Femoral Head by Affecting Bone Metabolism
Osteonecrosis of femoral head (ONFH) is a progressive hip joint disease without disease-modifying treatment. Lacking understanding of the pathophysiological process of ONFH has become the humper to develop therapeutic approach. Serum amyloid A (SAA) is an acute phase lipophilic protein during inflammation and we found that SAA is increased for the first time in the serum of ONFH patients through proteomic studies and quantitatively verified by ELISA. Treating rBMSCs with SAA inhibited the osteogenic differentiation via Wnt/β-catenin signaling pathway deactivation and enhanced the adipogenic differentiation via MAPK/PP...
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Editorial: Chronic Inflammation and Neurodegeneration in Retinal Disease
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation
Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice la...
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Evaluation of CML TKI Induced Cardiovascular Toxicity and Development of Potential Rescue Strategies in a Zebrafish Model
In this study, we established a zebrafish model to evaluate potential in vivo cardiovascular toxicity of TKIs. We treated the endothelium labeled Tg(kdrl:EGFP) transgenic zebrafish embryos with TKIs then performed confocal imaging to evaluate their vascular structure and function. We found that among FDA approved CML TKIs, ponatinib (the only approved TKI that is efficacious to T315I mutation) is the most toxic one. We then evaluated safety profiles of several clinical stage kinase inhibitors that can target T315I and found that HQP1351 treatment leads to vasculopathies similar to those induced by ponatinib while the allos...
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

CRISPA: A Non-viral, Transient Cas9 Delivery System Based on Reengineered Anthrax Toxin
Translating the CRISPR/Cas9 genome editing technology into clinics is still hampered by rather unspecific, unsafe and/or inconvenient approaches for the delivery of its main components - the Cas9 endonuclease and a guide RNA - into cells. Here, we describe the development of a novel transient and non-viral Cas9 delivery strategy based on the translocation machinery of the Bacillus anthracis anthrax toxin, PA (protective antigen). We show that Cas9 variants fused to the N-terminus of the lethal factor or to a hexahistidine tag are shuttled through channels formed by PA into the cytosol of human cells. As proof-of-principle,...
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways
This study investigated the neuroprotective effects of S. inappendiculata polyphenol rich extract (SiPE) against diabetic encephalopathy in rats and elucidated the potential mechanisms of action. Type 2 diabetes mellitus (T2DM) was induced using high fructose solution/intraperitoneal injection of streptozotocin and the diabetic rats were treated with SiPE (50, 100 and 200 mg/kg) for 8 weeks. Learning and memory functions were assessed using the Morris water and Y maze tests, depressive behaviour was evaluated using forced swimming and open field tests, while neuropathic pain assessment was assessed using hot plat...
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

BuqiTongluo Granule for Ischemic Stroke, Stable Angina Pectoris, Diabetic Peripheral Neuropathy with Qi Deficiency and Blood Stasis Syndrome: Rationale and Novel Basket Design
Conclusion: QDBS syndrome is a common phenotypic marker that was hypothesized to predict whether patients with multiple diseases would respond to this targeted therapy. No previous basket trial has assessed the potential efficacy of an herbal intervention for multiple diseases. The unique promise of the trial is its ability to exploit a disease phenotype to discover novel treatments for three diseases for which the root cause is unknown, complex, or multifactorial, and for which scientific understanding is insufficient to provide valid molecular targets. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Protective Effect of Oxytocin on Ventilator-Induced Lung Injury Through NLRP3-Mediated Pathways
Mechanical ventilation is an indispensable life-support treatment for acute respiratory failure in critically ill patients, which is generally believed to involve uncontrolled inflammatory responses. Oxytocin (OT) has been reported to be effective in animal models of acute lung injury. However, it is not clear whether Oxytocin has a protective effect on ventilator-induced lung injury (VILI). Therefore, in this study, we aimed to determine whether OT can attenuate VILI and explore the possible mechanism of this protection. To this end, a mouse VILI model was employed. Mice were pretreated with OT 30 min before the intr...
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

The Standard of Care Definitions on COVID-19 Pharmacological Clinical Trials: A Systematic Review
Conclusion: Our analysis shows that the findings emerging from several clinical trials regarding the efficacy and safety of pharmacological intervention for COVID-19 might be jeopardized by the quality of control arms. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Editorial: Cannabidiol Treatment in Neurotherapeutic Interventions
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Long-Term Use of Statins Lowering the Risk of Rehospitalization Caused by Ischemic Stroke Among Middle-Aged Hyperlipidemic Patients: A Population-Based Study
Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis.Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients>45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS ...
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Comprehensive Treatment of Trans-Arterial Chemoembolization Plus Lenvatinib Followed by Camrelizumab for Advanced Hepatocellular Carcinoma Patients
Conclusion:Trans-arterial chemoembolization plus lenvatinib and camrelizumab shows good results incontrolling tumour progression and prolonging median OS in patients with advanced HCC. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Myricetin Induces Autophagy and Cell Cycle Arrest of HCC by Inhibiting MARCH1-Regulated Stat3 and p38 MAPK Signaling Pathways
Myricetin is a type of natural flavonol known for its anticancer activity. However, the molecular mechanism of myricetin in anti-hepatocellular carcinoma (HCC) is not well defined. Previous studies indicated that downregulation of membrane-associated RING-CH finger protein 1 (MARCH1) contributed to the treatment of a variety of cancers. Whether the anticancer property of myricetin is associated with MARCH1 expression remains to be investigated. This research explored the anti-HCC mechanism of myricetin. Our results indicate that myricetin induces autophagy and arrests cell cycle at the G2/M phase to suppress the proliferat...
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Effect of Mahuang Fuzi and Shenzhuo Decoction on Idiopathic Membranous Nephropathy: A Multicenter, Nonrandomized, Single-Arm Clinical Trial
This study is a multicenter, nonrandomized, single-arm clinical trial carried out as per the objective performance criteria, with the target being set at 35.0%. 184 cases of patients suffering from idiopathic membranous nephropathy with Shaoyin Taiyin syndrome were collected. These patients were treated with Mahuang Fuzi and Shenzhuo Decoction with a follow-up period of 3 years. The 24-hour urine protein and blood albumin were observed, and the remission rates of the patients were compared with the target.Results: The mean follow-up time was 18 (12.5, 30) months, and the remission rate was 61.4%, which is a stati...
Source: Frontiers in Pharmacology - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

β-Adrenergic Receptor Inhibitor and Oncolytic Herpesvirus Combination Therapy Shows Enhanced Antitumoral and Antiangiogenic Effects on Colorectal Cancer
This study extended our previously observed combination effects of propranolol, a nonselective β-blocker, and the T1012G oncolytic virus into colorectal cancer models. A cell viability assay showed that cotreatment could induce synergistic killing effects on human and murine colorectal cell lines. Moreover, cotreatment caused sustained tumor regression compared with T1012G monotherapy or propranolol monotherapy in human HCT116 and murine MC38 tumor models. The propranolol activity was not via a direct effect on viral replication in vitro or in vivo. Western blotting showed that cotreatment significantly enhanced the e...
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Corrigendum: The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Beta-Adrenergic Blockade in Critical Illness
Catecholamine upregulation is a core pathophysiological feature in critical illness. Sustained catecholamine β-adrenergic induction produces adverse effects relevant to critical illness management. β-blockers (βB) have proposed roles in various critically ill disease states, including sepsis, trauma, burns, and cardiac arrest. Mounting evidence suggests βB improve hemodynamic and metabolic parameters culminating in decreased burn healing time, reduced mortality in traumatic brain injury, and improved neurologic outcomes following cardiac arrest. In sepsis, βB appear hemodynamically benign after acu...
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Bioactivities and Structure –Activity Relationships of Fusidic Acid Derivatives: A Review
Fusidic acid (FA) is a natural tetracyclic triterpene isolated from fungi, which is clinically used for systemic and local staphylococcal infections, including methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci infections. FA and its derivatives have been shown to possess a wide range of pharmacological activities, including antibacterial, antimalarial, antituberculosis, anticancer, tumor multidrug resistance reversal, anti-inflammation, antifungal, and antiviral activity in vivo and in vitro. The semisynthesis, structural modification and biological activities of FA derivatives have been exte...
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Influence of Cytochrome P450 2C19 Genotype on Helicobacter pylori Proton Pump Inhibitor-Amoxicillin-Clarithromycin Eradication Therapy: A Meta-Analysis
Background: Proton pump inhibitors (PPIs) are the first-line treatment for acid-related diseases. The pharmacokinetics and therapeutic efficacy of PPIs, however, are influenced by genetic factors such as variants in genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19 [CYP2C19]) and drug transporters. We performed a meta-analysis to evaluate the influence of CYP2C19 genotype and PPI class, PPI dose, treatment duration and clarithromycin dose on the cure rate of PPI-containing Helicobacter pylori eradication therapy.Methods: Randomized control trials (RCTs) investigating cure rates using a PPI-amoxicillin-cl...
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Doxorubicin-Loaded Tumor-Targeting Peptide-Decorated Polypeptide Nanoparticles for Treating Primary Orthotopic Colon Cancer
In this study, doxorubicin (DOX)-loaded tumor-targeting peptide-decorated mPEG-P(Phe-co-Cys) nanoparticles were developed to treat orthotopic colon cancer in mice. The peptide VATANST (STP) can specifically bind with vimentin highly expressed on the surface of colon cancer cells, thus achieving the tumor-targeting effects. The nanoparticles are core-shell structured, which can protect the loaded DOX while passing through the blood flow and increase the circulation time. The disulfide bonds within the nanoparticles are sensitive to the glutathione-rich microenvironment of tumor tissues. Rupture of disulfide bonds of the nan...
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Cost-Effectiveness of Testing for NS5A Resistance to Optimize Treatment of Elbasvir/Grazoprevir for Chronic Hepatitis C in China
Conclusions: Our results suggest prior assessment of NS5A sensitivity followed by optimizing treatment duration was an economic strategy. In addition, shortened 8-weeks treatment (no testing) was shown to be dominant with the SVR rate increased to 95%. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Running on Empty: Of Hypopinealism and Human Seasonality
The pineal hormone melatonin is the natural transducer of the environmental light–dark signal to the body. Although the responsiveness to photoperiod is well-conserved in humans, only about 25 percent of the human population experiences seasonal changes in behavior. As a consequence, humans seem to have adapted—at least partly—to the seasonal changes in day length. The aim of the study was to demonstrate that the individual melatonin deficit marker DOC (degree of pineal calcification) is related to variation of seasonal phenomena in humans. Out of 3,011 patients in which cranial computer tomography (cCT) ...
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

The Immunological Mechanisms and Immune-Based Biomarkers of Drug-Induced Liver Injury
Drug-induced liver injury (DILI) has become one of the major challenges of drug safety all over the word. So far, about 1,100 commonly used drugs including the medications used regularly, herbal and/or dietary supplements, have been reported to induce liver injury. Moreover, DILI is the main cause of the interruption of new drugs development and drugs withdrawn from the pharmaceutical market. Acute DILI may evolve into chronic DILI or even worse, commonly lead to life-threatening acute liver failure in Western countries. It is generally considered to have a close relationship to genetic factors, environmental risk factors,...
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Innovation in Informatics to Improve Clinical Care and Drug Accessibility for Rare Diseases in China
Conclusion: A national strategy and the coordinating mechanism is the key to success in the improvement of Chinese rare disease clinical care and drug accessibility. Application of innovative informatics solutions can help accelerate the process, improve quality and increase efficiency. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Schisandrin B Antagonizes Cardiotoxicity Induced by Pirarubicin by Inhibiting Mitochondrial Permeability Transition Pore (mPTP) Opening and Decreasing Cardiomyocyte Apoptosis
Conclusion: SchB has an obvious protective effect on THP-induced cardiotoxicity. The mechanism may be closely related to the protection of mitochondrial function, inhibition of mPTP opening, and alleviation of oxidative stress and apoptosis of cardiomyocytes. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Attenuation of Circulating Trimethylamine N-Oxide Prevents the Progression of Cardiac and Renal Dysfunction in a Rat Model of Chronic Cardiorenal Syndrome
Chronic heart failure (HF) frequently causes progressive decline in kidney function, known as cardiorenal syndrome-2 (CRS2). Current treatment options for CRS2 remain unacceptably limited. Trimethylamine-N-oxide (TMAO), a metabolite of gut microbiota, has recently been implicated in the pathogenesis of both HF and chronic kidney disease. Here we examined whether circulating TMAO is elevated in CRS2 and if so, whether attenuation of circulating TMAO would ameliorate the progression of CRS2. Sprague-Dawley rats underwent surgery for myocardial infarction (MI) or sham (week 0) followed by subtotal (5/6) nephrectomy (STNx) or ...
Source: Frontiers in Pharmacology - October 14, 2021 Category: Drugs & Pharmacology Source Type: research

Effects of Volume-Price Contracts on Pharmaceutical Prices: A Retrospective Comparative Study of Public Hospitals in Hubei of China
Conclusion: The volume-price contract initiative has the potential to bring down the price of pharmaceutical supplies. Higher responses from the domestic suppliers are evident. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 14, 2021 Category: Drugs & Pharmacology Source Type: research

Mechanisms Underlying the Effects of Lianhua Qingwen on Sepsis-Induced Acute Lung Injury: A Network Pharmacology Approach
Conclusion: This study reveals that LHQW may alleviate LPS-induced ALI via inhibiting p53-mediated intrinsic apoptosis pathways. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 14, 2021 Category: Drugs & Pharmacology Source Type: research

Contributions of UDP-Glucuronosyltransferases to Human Hepatic and Intestinal Metabolism of Ticagrelor and Inhibition of UGTs and Cytochrome P450 Enzymes by Ticagrelor and its Glucuronidated Metabolite
Ticagrelor is the first reversibly binding, direct-acting, oral P2Y12 receptor inhibitor. The contribution of UDP-glucuronosyltransferases (UGTs) enzymes to the metabolism of ticagrelor to its glucuronide conjugation, ticagrelor-O-glucuronide, in human liver microsomes (HLM) and human intestinal microsomes (HIM), was well characterized in the current study. The inhibition potential of human major UGTs by ticagrelor and ticagrelor-O-glucuronide was explored. The inhibitory effects of ticagrelor-O-glucuronide on cytochrome P450s (CYPs) enzymes were investigated as well. Ticagrelor glucuronidation exhibits substrate inhibitio...
Source: Frontiers in Pharmacology - October 14, 2021 Category: Drugs & Pharmacology Source Type: research

Path4Drug: Data Science Workflow for Identification of Tissue-Specific Biological Pathways Modulated by Toxic Drugs
In this study, we present a computational technique that employs the propagation of drug-protein interactions to connect compounds to biological pathways. Target profiles for drugs were built by retrieving drug target proteins from public repositories such as ChEMBL, DrugBank, IUPHAR, PharmGKB, and TTD. Subsequent enrichment test of the protein pool using Reactome revealed potential pathways affected by the drugs. Furthermore, an optional tissue filter utilizing the Human Protein Atlas was applied to identify tissue-specific pathways. The analysis pipeline was implemented in an open-source KNIME workflow called Path4Drug t...
Source: Frontiers in Pharmacology - October 14, 2021 Category: Drugs & Pharmacology Source Type: research

Parkia speciosa Hassk. Empty Pod Extract Alleviates Angiotensin II-Induced Cardiomyocyte Hypertrophy in H9c2 Cells by Modulating the Ang II/ROS/NO Axis and MAPK Pathway
This study investigated the activity of P. speciosa empty pod extract against cardiomyocyte hypertrophy in H9c2 cardiomyocytes exposed to angiotensin II (Ang II). In particular, its role in modulating the Ang II/reactive oxygen species/nitric oxide (Ang II/ROS/NO) axis and mitogen-activated protein kinase (MAPK) pathway was examined. Treatment with the extract (12.5, 25, and 50 μg/ml) prevented Ang II-induced increases in cell size, NADPH oxidase activity, B-type natriuretic peptide levels, and reactive oxygen species and reductions in superoxide dismutase activity. These were comparable to the effects of the valsa...
Source: Frontiers in Pharmacology - October 14, 2021 Category: Drugs & Pharmacology Source Type: research

Traditional Uses, Chemistry, Pharmacology, Toxicology and Quality Control of Alhagi sparsifolia Shap.: A Review
Alhagi sparsifolia Shap. (Kokyantak) is a ethnic medicine used in the Uyghur traditional medicine system for the treatment of colds, rheumatic pains, diarrhea, stomach pains, headaches, and toothaches, in addition to being an important local source of nectar and high-quality forage grass, and playing a crucial role in improving the ecological environment. Currently, approximately 178 chemical constituents have been identified from A. sparsifolia, including flavonoids, alkaloids, phenolic acids, and 19 polysaccharides. Pharmacological studies have already confirmed that A. sparsifolia has antioxidant, anti-tumor, anti-neuro...
Source: Frontiers in Pharmacology - October 14, 2021 Category: Drugs & Pharmacology Source Type: research