Eupafolin Suppresses Esophagus Cancer Growth by Targeting T-LAK Cell-Originated Protein Kinase
Eupafolin is the main bioactive component extracted from the traditional Chinese medicine Ay Tsao (Artemisia vulgaris L.), and its anti-tumor activity has had been studied in previous researches. T-LAK cell-originated protein kinase (TOPK) belongs to serine/threonine protein kinase and is highly expressed in several cancer cells and tissues, such as colon cancer, lung cancer, esophagus cancer, and so on. Therefore, it was recognized as an important target for treating tumors. Nowadays, we found that eupafolin suppressed TOPK activities at the first time in vitro and in vivo. The cells study indicated that eupafolin suppres...
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Cerebrolysin Ameliorates Focal Cerebral Ischemia Injury Through Neuroinflammatory Inhibition via CREB/PGC-1 α Pathway
In conclusion, CBL ameliorated cerebral ischemia injury through reducing neuroinflammation partly via the activation of CREB/PGC-1α pathway and may play a therapeutic role as anti-neuroinflammatory agents in the brain disorders associated with neuroinflammation. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Comparison of Healthcare Utilization and Costs Between RA Patients Receiving Biological and Conventional Synthetic DMARDs: A Nationwide Population-Based Cohort Study in Taiwan
Conclusion: Although total costs increased as a result of introducing biologics in RA treatment, biologics have undoubtedly given rise to the benefits of reduced healthcare utilization. The increase in medication costs from biologics was offset by the lower costs of healthcare utilization. Our findings suggest that the medication costs of biologics may be alleviated by an improvement in clinical outcomes. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Surprising Anticancer Activities of Psychiatric Medications: Old Drugs Offer New Hope for Patients With Brain Cancer
Despite decades of research and major efforts, malignant brain tumors remain among the deadliest of all cancers. Recently, an increasing number of psychiatric drugs has been proven to possess suppressing activities against brain tumors, and rapid progress has been made in understanding the potential mechanisms of action of these drugs. In particular, the traditional mood stabilizer valproic acid, the widely used antidepressants fluoxetine and escitalopram oxalate, and the atypical psychiatric drug aripiprazole have demonstrated promise for application in brain tumor treatment strategies through multiple lines of laboratory...
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Screening for Potential Active Components of Fangji Huangqi Tang on the Treatment of Nephrotic Syndrome by Using Integrated Metabolomics Based on “Correlations Between Chemical and Metabolic Profiles”
This study demonstrated a promising way to elucidate the active chemical material basis of TCM prescription. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Simultaneous Determination of Five Alkaloids by HPLC-MS/MS Combined With Micro-SPE in Rat Plasma and Its Application to Pharmacokinetics After Oral Administration of Lotus Leaf Extract
An environment-friendly and efficient method for simultaneous determination of five alkaloids (nunciferine, O-nornuciferin, liriodenine, armepavine, and pronuciferine) in rat plasma was established by HPLC-MS/MS associated with micro-solid phase extraction (micro-SPE). The plasma sample was pretreated by using micro-SPE columns filled with polymer materials PEP-2 and eluted by little organic solvent (400 µl acetonitrile). The five alkaloids were separated with acetonitrile and 0.1% formic acid aqueous solution on Eclipse plus C18 column. The mode of positive electrospray ionization was used to measure the anal...
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Eupafolin Suppresses Esophagus Cancer Growth by Targeting T-LAK Cell-Originated Protein Kinase Protein Kinase
Eupafolin is the main bioactive component extracted from the traditional Chinese medicine Ay Tsao (Artemisia vulgaris L.), and its anti-tumor activity has had been studied in previous researches. T-LAK cell-originated protein kinase (TOPK) belongs to serine/threonine protein kinase and is highly expressed in several cancer cells and tissues, such as colon cancer, lung cancer, esophagus cancer, and so on. Therefore, it was recognized as an important target for treating tumors. Nowadays, we found that eupafolin suppressed TOPK activities at the first time in vitro and in vivo. The cells study indicated that eupafolin suppres...
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Minocycline Ameliorates Depressive-Like Behavior and Demyelination Induced by Transient Global Cerebral Ischemia by Inhibiting Microglial Activation
Global cerebral ischemia (GCI) commonly occurs in the elderly. Subcortical white matter lesions and oligodendrocyte (OLG) loss caused by cerebral ischemia have been implicated in the development of post-ischemic depression and cognitive impairment. OLGs are necessary for axonal myelination; the disrupted differentiation of OLG progenitor cells (OPCs) is associated with impaired remyelination. Evidence has indicated that increased levels of inflammatory cytokines released from activated microglia induce depression-like behaviors by affecting neurotransmitter pathways, but the mechanisms remain elusive. We explored the poten...
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Cannabis for Neuropathic Pain in Multiple Sclerosis —High Expectations, Poor Data
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Pterostilbene, An Active Constituent of Blueberries, Suppresses Proliferation Potential of Human Cholangiocarcinoma via Enhancing the Autophagic Flux
Conclusion: Taken together, our findings indicate that pterostilbene, through the induction of autophagic flux, acts as an anti-cancer agent against CCA cells. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Lithraea caustic (Litre) Extract Promotes an Antitumor Response Against B16 Melanoma
Melanoma immunotherapy, specifically the autotransplant of dendritic cells charged with tumors antigens, has shown promising results in clinical trials. The positive clinical effects of this therapy have been associated to increased Th17 response and delayed-type hypersensitivity (DTH) against to tumor antigens. Some synthetic compounds, such as diphenylcyclopropenone (DPCP), are capable of triggering a DTH response in cutaneous malignancies and also to induce clinically relevant effects against melanoma. In this work, we evaluated Litre extract (LExT), a standardized extract of a Chilean stinging plant, Lithraea caustic (...
Source: Frontiers in Pharmacology - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

PTC-209 Anti-Cancer Effects Involved the Inhibition of STAT3 Phosphorylation
Conclusion: Our findings identify PTC-209 as a promising anticancer agent for the treatment of solid tumors either alone and/or in combination with the standard cytotoxic drugs cisplatin and camptothecin and the natural product Frondoside-A. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 21, 2019 Category: Drugs & Pharmacology Source Type: research

Small-Molecule Modulators of Sigma1 and Sigma2/TMEM97 in the Context of Cancer: Foundational Concepts and Emerging Themes
There are two known subtypes of the so-called sigma receptors, Sigma1 and Sigma2. Sigma1 (encoded by the SIGMAR1 gene and also known as Sigma-1 receptor, S1R) is a unique pharmacologically regulated integral membrane chaperone or scaffolding protein that allosterically modulates the activity of its associated proteins. Sigma2, recently identified as transmembrane protein 97 (TMEM97), is an integral membrane protein implicated in cellular cholesterol homeostasis. A number of publications over the past two decades have suggested a role for both sigma proteins in tumor biology. Although there is currently no clinically used a...
Source: Frontiers in Pharmacology - October 21, 2019 Category: Drugs & Pharmacology Source Type: research

The TRPA1 Channel in the Cardiovascular System: Promising Features and Challenges
The transient receptor potential ankyrin 1 (TRPA1) channel is a calcium-permeable nonselective cation channel in the plasma membrane that belongs to the transient receptor potential (TRP) channel superfamily. Recent studies have suggested that the TRPA1 channel plays an essential role in the development and progression of several cardiovascular conditions, such as atherosclerosis, heart failure, myocardial ischemia–reperfusion injury, myocardial fibrosis, arrhythmia, vasodilation, and hypertension. Activation of the TRPA1 channel has a protective effect against the development of atherosclerosis. Furthermore, TRPA1 c...
Source: Frontiers in Pharmacology - October 18, 2019 Category: Drugs & Pharmacology Source Type: research

Ocular Pharmacological Profile of Hydrocortisone in Dry Eye Disease
To investigate the ocular pharmacological profile of hydrocortisone (HC) using in vitro and in vivo models of dry eye disease. Rabbit corneal epithelial cells (SIRCs) were used to assess the effect of HC in two paradigms of corneal damage: hyperosmotic stress and scratch-wound assay. Dry eye was induced in albino rabbits by topical administration of atropine sulfate or by injection of concanavalin A (ConA) into the lacrimal gland. TNFα, TNF-related apoptosis-inducing ligand (TRAIL), IL-1β, and IL-8 were determined by ELISA or western blot in a corneal damage hyperosmotic in vitro model, with or without HC treatm...
Source: Frontiers in Pharmacology - October 18, 2019 Category: Drugs & Pharmacology Source Type: research

Immunomodulatory Activity of Tyrosine Kinase Inhibitors to Elicit Cytotoxicity Against Cancer and Viral Infection
Tyrosine kinase inhibitors (TKIs) of aberrant tyrosine kinase (TK) activity have been widely used to treat chronic myeloid leukemia (CML) for decades in clinic. An area of growing interest is the reported ability of TKIs to induce immunomodulatory effects with anti-tumor and anti-viral activity, which appears to be mediated by directly or indirectly acting on immune cells. In selected cases of patients with CML, TKI treatment may be interrupted and a non-drug remission may be observed. In these patients, an immune mechanism of increased anti-tumor cytotoxic activity induced by chronic administration of TKIs has been sugges...
Source: Frontiers in Pharmacology - October 18, 2019 Category: Drugs & Pharmacology Source Type: research

Importance of Quality Assessment in Clinical Research in Japan
Conclusions: The number of published papers does not correspond to paper quality. When assessing an institution’s ability to perform clinical research, an assessment of paper quality should be included along with the number of published papers. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 18, 2019 Category: Drugs & Pharmacology Source Type: research

Cytochrome P450 1A2 Is Incapable of Oxidizing Bilirubin Under Physiological Conditions
Conclusion: Our results indicated that the region-specific expression of CYP1A2 increased during development, but CYP family enzymes were physiologically incapable of metabolizing BR. The ability of CYPs to oxidize BR may be triggered by CYP inducers. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 18, 2019 Category: Drugs & Pharmacology Source Type: research

Methylprednisolone Decreases Mitochondria-Mediated Apoptosis and Autophagy Dysfunction in Hepatocytes of Experimental Autoimmune Hepatitis Model via the Akt/mTOR Signaling
In conclusion, MP ameliorated mitochondria-mediated apoptosis and autophagy dysfunction in ConA-induced hepatocyte injury in vivo and in vitro via the Akt/mTOR signaling pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 18, 2019 Category: Drugs & Pharmacology Source Type: research

Zearalenone and ß-Zearalenol But Not Their Glucosides Inhibit Heat Shock Protein 90 ATPase Activity
In conclusion, the mycotoxin ZEN has a very prominent target in plants, HSP90, but it can be inactivated by glycosylation. This may explain why there is little evidence for a virulence function of ZEN in host plants. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 18, 2019 Category: Drugs & Pharmacology Source Type: research

Construction and Analysis of circRNA-miRNA-mRNA Molecular Regulatory Networks During Herba Gelsemium elegans Intoxication
Gelsemium elegans (Gardner & Champ.) Benth. (GE) has therapeutic effects for pain and malignant tumors but also has high toxicity. Its mechanism of toxicity has not yet been fully clarified, thus limiting its application. Meanwhile, evidence has shown that circRNAs are closely related to the progression of disease. However, very little is known about their expression profiles during intoxication. In this paper, circRNA/mRNA microarrays were respectively performed to detect their expression profiles in mice with acute GE intoxication versus normal controls. CircRNAs were verified by qRT-PCR in subsequent experiments. A ...
Source: Frontiers in Pharmacology - October 17, 2019 Category: Drugs & Pharmacology Source Type: research

Patchouli Essential Oil and Its Derived Compounds Revealed Prebiotic-Like Effects in C57BL/6J Mice
Pogostemon cablin (Blanco) Benth (PC) is a Chinese medicinal plant traditionally used for the treatment of gastrointestinal symptoms. To investigate the prebiotic effect of patchouli essential oil (PEO) and its derived compounds through the modulation of gut microbiota (GM). C57BL/6J mice were treated with the PEO and three active components of PEO, i.e. patchouli alcohol (PA), pogostone (PO) and β-patchoulene (β-PAE) for 15 consecutive days. Fecal samples and mucosa were collected for GM biomarkers studies. PEO, PA, PO, and β-PAE improve the gut epithelial barrier by altering the status of E-cadherin vs. N-...
Source: Frontiers in Pharmacology - October 17, 2019 Category: Drugs & Pharmacology Source Type: research

Efficacy and Safety of Raltegravir-Based Dual Therapy in AIDS Patients: A Meta-Analysis of Randomized Controlled Trials
Conclusion: We found that the simplified regimen was noninferior to TT regimen in regard to viral suppression. Furthermore, the simplified DT regimen had a better CD4 cell count and lower adverse events than the TT regimen. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 17, 2019 Category: Drugs & Pharmacology Source Type: research

Notoginsenoside R1 for Organs Ischemia/Reperfusion Injury: A Preclinical Systematic Review
Notoginsenoside R1 (NGR1) exerts pharmacological actions for a variety of diseases such as myocardial infarction, ischemic stroke, acute renal injury, and intestinal injury. Here, we conducted a preclinical systematic review of NGR1 for ischemia reperfusion (I/R) injury. Eight databases were searched from their inception to February 23rd, 2019; Review Manager 5.3 was applied for data analysis. CAMARADES 10-item checklist and cell 10-item checklist were used to evaluate the methodological quality. Twenty-five studies with 304 animals and 124 cells were selected. Scores of the risk of bias in animal studies ranged from 3 to ...
Source: Frontiers in Pharmacology - October 17, 2019 Category: Drugs & Pharmacology Source Type: research

miR-128 Functions as an OncomiR for the Downregulation of HIC1 in Breast Cancer
Hypermethylated in cancer 1 (HIC1) is continually decreased in breast cancer. However, the underlying molecular basis of the upstream regulation of HIC1 remains elusive. Here, we showed that HIC1 was downregulated in breast cancer tissues. Bioinformatics analysis identified that miR-128 might potentially target HIC1. HIC1 was proved as the target gene of miR-128 by overexpressing or knocking down miR-128. Additionally, we observed that HIC1 suppression by miR-128 increased cell invasion, proliferation, and reduced apoptosis. Lastly, we found that miR-128 accelerated tumor growth in xenograft mice by inhibiting HIC1. Altoge...
Source: Frontiers in Pharmacology - October 17, 2019 Category: Drugs & Pharmacology Source Type: research

Phillyrin Attenuates Osteoclast Formation and Function and Prevents LPS-Induced Osteolysis in Mice
In this study, we reported for the first time that phillyrin (Phil), an active ingredient extracted from forsythia, significantly inhibited RANKL-induced osteoclastogenesis and bone resorption in vitro and protected against lipopolysaccharide-induced osteolysis in vivo. Further molecular investigations demonstrated that Phil effectively blocked RANKL-induced activations of c-Jun N-terminal kinase and extracellular signal-regulated kinase, which suppressed the expression of c-Fos and nuclear factor of activated T-cells cytoplasmic 1. Taken together, these data suggested that Phil might be a potential antiosteoclastogenesis ...
Source: Frontiers in Pharmacology - October 17, 2019 Category: Drugs & Pharmacology Source Type: research

Adverse Events of Concurrent Immune Checkpoint Inhibitors and Antiangiogenic Agents: A Systematic Review
Conclusions: Concurrent use of ICIs and antiangiogenic agents shows potential treatment-related toxicity. Further research is required to compare the efficacy and safety of the combination regimen and corresponding monotherapy and identify predictive biomarkers, as well as explore dose, duration, and sequencing schedules of drugs. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 17, 2019 Category: Drugs & Pharmacology Source Type: research

Sleep and the Pharmacotherapy of Alcohol Use Disorder: Unfortunate Bedfellows. A Systematic Review With Meta-Analysis
Conclusion: We included 26 studies: only three studies focused on sleep as a main outcome, two with polysomnography (objective measurement), and one with subjective self-reported sleep, while all the other studies reported sleep problems among the adverse effects (subjective report). The only study available on disulfiram showed reduced REM sleep. Acamprosate showed no/little effect on self-reported sleep but improved sleep continuity and architecture measured by polysomnography. The two opioidergic drugs naltrexone and nalmefene had mainly detrimental effect on sleep, giving increased insomnia and/or somnolence compared w...
Source: Frontiers in Pharmacology - October 17, 2019 Category: Drugs & Pharmacology Source Type: research

Toxicity Study of 28-Day Subcutaneous Injection of Arctigenin in Beagle Dogs
Our previous studies have investigated the systematic pharmacokinetic characteristics, biological activities, and toxicity of arctigenin. In this research, the potential toxicities of arctigenin in beagle dogs were investigated via repeated 28-day subcutaneous injections. Beagle dogs were randomly divided into control, vehicle [polyethylene glycol (PEG)], and arctigenin 6, 20, 60 mg/kg treated groups. The whole experimental period lasted 77 days, including adaptive period (35 days), drug exposure period (animals were treated with saline, PEG, or arctigenin for 28 consecutive days), and recovery period (14 days). Arctigenin...
Source: Frontiers in Pharmacology - October 16, 2019 Category: Drugs & Pharmacology Source Type: research

An Improved Enzyme-Linked Focus Formation Assay Revealed Baloxavir Acid as a Potential Antiviral Therapeutic Against Hantavirus Infection
Hantaviruses, etiologic pathogens responsible for two severe human diseases, exist in areas ranging from Eurasia to America and remain global public health concerns. Conventionally, plaque formation assays have been used for hantavirus titering. However, hantaviruses replicate slowly within cells and produce minimal cytopathic effects, making this technique difficult to master. The improved enzyme-linked immunosorbent assay-based antigen detection method is easier to perform but is still time consuming. Here, we established an enzyme-linked focus formation assay (FFA) for Hantaan virus titering that is twice as fast as tra...
Source: Frontiers in Pharmacology - October 16, 2019 Category: Drugs & Pharmacology Source Type: research

FGF10 Enhances Peripheral Nerve Regeneration via the Preactivation of the PI3K/Akt Signaling-Mediated Antioxidant Response
In this study, we aimed to investigate the underlying therapeutic effects of FGF10 on nerve regeneration and functional recovery after PNI and to explore the associated mechanism. Our results showed that FGF10 administration promoted axonal regeneration and functional recovery after nerve damage. Moreover, exogenous FGF10 treatment also prevented SCs from excessive oxidative stress-induced apoptosis, which was probably related to the activation of phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling. The inhibition of the PI3K/Akt pathway by the specific inhibitor LY294002 partially reversed the therapeutic ...
Source: Frontiers in Pharmacology - October 16, 2019 Category: Drugs & Pharmacology Source Type: research

Physiological and Pharmaceutical Considerations for Rectal Drug Formulations
Although the oral route is the most convenient route for drug administration, there are a number of circumstances where this is not possible from either a clinical or pharmaceutical perspective. In these cases, the rectal route may represent a practical alternative and can be used to administer drugs for both local and systemic actions. The environment in the rectum is considered relatively constant and stable and has low enzymatic activity in comparison to other sections of the gastrointestinal tract. In addition, drugs can partially bypass the liver following systemic absorption, which reduces the hepatic first-pass effe...
Source: Frontiers in Pharmacology - October 16, 2019 Category: Drugs & Pharmacology Source Type: research

Potassium Intake Prevents the Induction of the Renin-Angiotensin System and Increases Medullary ACE2 and COX-2 in the Kidneys of Angiotensin II-Dependent Hypertensive Rats
In this report we evaluate the expression of AGT, ACE, medullary prorenin/renin, ACE2, kallikrein and cyclooxygenase-2 (COX-2) in Ang II-infused rats fed with high K+ diet (2%) for 14 days. Dietary K+ enhances diuresis in non-infused and in Ang II-infused rats. The rise in systolic blood pressure in Ang II-infused rats was attenuated by dietary K+. Ang II-infused rats showed increased renal protein levels of AGT, ACE and medullary prorenin and renin. This effect was attenuated in the Ang II + K+ group. Ang II infusion decreased ACE2 compared to the control group; however, K+ diet prevented this effect in the renal medulla....
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Synthesis, Biological Evaluation, and Mode of Action of Pulsatilla Saponin D Derivatives as Promising Anticancer Agents
A series of ester and amide derivatives of triterpenoid saponin Pulsatilla saponin D (PSD) were designed, synthesized, and evaluated for their antiproliferative activity. Compounds 1 and 6 displayed 1.7–8.3 times more potent cytotoxicity (IC50 = 1.2–4.7 and 1.7–4.5 μM, respectively) against five human tumor cell lines (SMMC-7721, MCF-7, NCI-H460, A549, and HCT-116) in vitro and lower acute toxicity to mice in vivo than did PSD. Furthermore, compound 6 was observed to show potent tumor growth inhibition against mice H22 hepatocellular cells (49.8% at 20 mg/kg) and induce cell cycle at G1 phase and apopt...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Growth Inhibitory Activity of Callicarpa americana Leaf Extracts Against Cutibacterium acnes
This study investigated the C. acnes inhibitory activity of Callicarpa americana leaves, a native Southeastern United States shrub historically used by Native Americans to treat fever, stomachache, and pruritis. Flash chromatography fractions of the ethyl acetate-soluble C. americana ethanol leaf extract (649C-F9 and 649C-F13) exhibited MICs ranging from 16 to 32 µg ml−1 and IC50 range of 4–32 μg ml−1 against a panel of 10 distinct C. acnes isolates. Cytotoxicity against an immortalized human keratinocyte cell line (HaCaTs) skin was detected at more than eight times the dose required for growth i...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Mitigating the Impact of Admixtures in Thai Herbal Products
This study aims to clarify the nature and extent of species admixtures reported in the Thai herbal trade market and discuss the potential reasons for such adulteration. In the broader context of species admixtures, we strongly propose the establishment of multiple herbal crude drug repositories that can be developed to facilitate the use of comparative identity tests by industry, traders, and researchers to maintain authentic natural health product (NHP) standards and to certify the authenticity of NHPs. The proposition of the establishment of centralized testing (CT) could be a promising initiative in Thailand for the dev...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Genotype –Phenotype Association Analysis Reveals New Pathogenic Factors for Osteogenesis Imperfecta Disease
Osteogenesis imperfecta (OI), mainly caused by structural abnormalities of type I collagen, is a hereditary rare disease characterized by increased bone fragility and reduced bone mass. Clinical manifestations of OI mostly include multiple repeated bone fractures, thin skin, blue sclera, hearing loss, cardiovascular and pulmonary system abnormalities, triangular face, dentinogenesis imperfecta (DI), and walking with assistance. Currently, 20 causative genes with 18 subtypes have been identified for OI, of them, variations in COL1A1 and COL1A2 have been demonstrated to be major causative factors to OI. However, the complexi...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

2-APB and CBD-Mediated Targeting of Charged Cytotoxic Compounds Into Tumor Cells Suggests the Involvement of TRPV2 Channels
Targeted delivery of therapeutic compounds to particular cell types such that they only affect the target cells is of great clinical importance since it can minimize undesired side effects. For example, typical chemotherapeutic treatments used in the treatment of neoplastic disorders are cytotoxic not only to cancer cells but also to most normal cells when exposed to a critical concentration of the compound. As such, many chemotherapeutics exhibit severe side effects, often prohibiting their effective use in the treatment of cancer. Here, we describe a new means for facilitated delivery of a clinically used chemotherapy co...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Neferine Attenuates Acute Kidney Injury by Inhibiting NF- κB Signaling and Upregulating Klotho Expression
Conclusion: Neferine mitigated renal injury in AKI models, perhaps by suppressing the activation of NF-κB and upregulating the expression of Klotho. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Antibiotic Treatment of Suspected and Confirmed Neonatal Sepsis Within 28 Days of Birth: A Retrospective Analysis
This study aims to retrospectively describe and compare treatments of blood culture-confirmed and unconfirmed, but suspected, sepsis within the University of Utah Hospital system. Electronic health records were obtained from 1,248 neonates from January 1, 2006, to December 31, 2017. Sepsis was categorized into early-onset (≤3 days of birth, EOS) and late-onset (>3 and ≤28 days of birth, LOS) and categorized as culture-confirmed sepsis if a pathogen was cultured from the blood and unconfirmed if all blood cultures were negative with no potentially contaminated blood cultures. Of 1,010 neonates in the EOS cohort, 23...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Chinese Herbal Formula (CHF03) Attenuates Non-Alcoholic Fatty Liver Disease (NAFLD) Through Inhibiting Lipogenesis and Anti-Oxidation Mechanisms
In this study, ICR male mice were fed a high-fat diet (HFD) in vivo and the AML12 cells were treated with palmitic acid (PA) in vitro. We explore the protective effect and potential mechanism of Chinese Herbal Formula (CHF03) against NAFLD by HE staining, transmission Electron Microscopy assay, Western blotting, and gene expression. In vivo, oxidative stress markers (GSH, GSH-px, MDA, SOD, and CAT) confirmed that CHF03 alleviated oxidative stress and abundance of NF-κB proteins indicating a reduction in inflammation and oxidative stress. The lower protein abundance of ACACA and FASN indicated a preventive effect on l...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Variability in Loss of Multiple Enzyme Activities Due to the Human Genetic Variation P284T Located in the Flexible Hinge Region of NADPH Cytochrome P450 Oxidoreductase
Cytochromes P450 located in the endoplasmic reticulum require NADPH cytochrome P450 oxidoreductase (POR) for their catalytic activities. Mutations in POR cause multiple disorders in humans related to the biosynthesis of steroid hormones and also affect drug-metabolizing cytochrome P450 activities. Electron transfer in POR occurs from NADH to FAD to FMN, and the flexible hinge region in POR is essential for domain movements to bring the FAD and FMN close together for electron transfer. We tested the effect of variations in the hinge region of POR to check if the effects would be similar across all redox partners or there wi...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Induction Apoptosis of Erinacine A in Human Colorectal Cancer Cells Involving the Expression of TNFR, Fas, and Fas Ligand via the JNK/p300/p50 Signaling Pathway With Histone Acetylation
This study found that treatment with erinacine A not only triggers the activation of extrinsic apoptosis pathways (TNFR, Fas, FasL, and caspases) but also suppresses the expression of antiapoptotic molecules Bcl-2 and Bcl-XL via a time-dependent manner in DLD-1 cells. Furthermore, phosphorylation of Jun N-terminus kinase (JNK1/2), NFκB p50, and p300 is involved in erinacine A–induced cancer cell apoptosis. Inhibition of these signaling pathways by kinase inhibitors blocks erinacine A–induced transcriptional activation implicates histone H3K9K14ac (Acetyl Lys9/Lys14) of the TNFR, Fas, and FasL as promoters...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

In Vitro Use of Cellular Synthetic Machinery for Biosensing Applications
The application of biosensors is expanding in diverse fields due to their high selectivity and sensitivity. Biosensors employ biological components for the recognition of target analytes. In addition, the amplifying nature of biosynthetic processes can potentially be harnessed to for biological transduction of detection signals. Recent advances in the development of highly productive and cost-effective cell-free synthesis systems make it possible to use these systems as the biological transducers to generate biosensing signals. This review surveys recent developments in cell-free biosensors, focusing on the newly devised m...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Ginsenoside Rb1 Induces Beta 3 Adrenergic Receptor –Dependent Lipolysis and Thermogenesis in 3T3-L1 Adipocytes and db/db Mice
In conclusion, we suggest Rb1 as a potential lipolytic and thermogenic therapeutic agent which can be used for obesity treatment. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Oxidized Lipids in Persistent Pain States
Chemotherapy, nerve injuries, or diseases like multiple sclerosis can cause pathophysiological processes of persistent and neuropathic pain. Thereby, the activation threshold of ion channels is reduced in peripheral sensory neurons to normally noxious stimuli like heat, cold, acid, or mechanical due to sensitization processes. This leads to enhanced neuronal activity, which can result in mechanical allodynia, cold allodynia, thermal hyperalgesia, spontaneous pain, and may initiate persistent and neuropathic pain. The treatment options for persistent and neuropathic pain patients are limited; for about 50% of them, current ...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway
Background: Effective interventions to improve the outcome of patients subjected to myocardial ischemia reperfusion (MI/R) are urgent in clinical settings. Tanshinone IIA (TSA) is reported to attenuate myocardial injury and improve ventricular remodeling post MI/R. Here, we evaluated the efficacy of AFC1 compound that is similar to TSA structure in murine MI/R models. We found that AFC1 had a comparable effect of improving murine cardiac function after MI/R while it was superior to TSA in safety profile. Administration of AFC1 reduced reactive oxygen species (ROS) production, inflammatory cells infiltration, and the expres...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Systems Pharmacology-Based Method to Assess the Mechanism of Action of Weight-Loss Herbal Intervention Therapy for Obesity
Obesity is a multi-factorial chronic disease that has become a serious, prevalent, and refractory public health challenge globally because of high rates of various complications. Traditional Chinese medicines (TCMs) as a functional food are considered to be a valuable and readily available resource for treating obesity because of their better therapeutic effects and reduced side effects. However, their “multi-compound” and “multi-target” features make it extremely difficult to interpret the potential mechanism underlying the anti-obesity effects of TCMs from a holistic perspective. An innovative sys...
Source: Frontiers in Pharmacology - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Piperlongumine, a Novel TrxR1 Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cells by ROS-Mediated ER Stress
We report that PL may interact with thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, and induce reactive oxygen species (ROS)-mediated apoptosis in HCC cells. Our results suggest that PL induces a lethal endoplasmic reticulum (ER) stress response in HCC cells by targeting TrxR1 and increasing intracellular ROS levels. Notably, PL treatment reduces TrxR1 activity and tumor cell burden in vivo. Additionally, TrxR1 is significantly upregulated in existing HCC databases and available HCC clinical specimens. Taken together, these results suggest PL as a novel anticancer candidate...
Source: Frontiers in Pharmacology - October 14, 2019 Category: Drugs & Pharmacology Source Type: research

The Modulatory Properties of Astragalus membranaceus Treatment on Triple-Negative Breast Cancer: An Integrated Pharmacological Method
Conclusion: This study provides a rational approach to discovering compounds with a polypharmacology-based therapeutic value. Our data established that APS intervenes with TNBC cell invasion, proliferation, and apoptosis via the PIK3CG/AKT/BCL2 pathway and could thus offer a promising therapeutic strategy for TNBC. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 14, 2019 Category: Drugs & Pharmacology Source Type: research