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Frontiers in Pharmacology

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https://www.readbyqxmd.com/read/27909407/the-tlr4-active-morphine-metabolite-morphine-3-glucuronide-does-not-elicit-macrophage-classical-activation-in-vitro
#1
Samira Khabbazi, Nan Xie, Wenjun Pu, Yannick Goumon, Marie-Odile Parat
Macrophages are abundant in the tumor microenvironment where they adopt a pro-tumor phenotype following alternative polarization induced by paracrine factors from cancer and stromal cells. In contrast, classically activated macrophages have tumoricidal activities, such that the polarization of tumor-associated macrophages has become a novel therapeutic target. Toll-like receptor 4 engagement promotes classical activation of macrophages, and recent literature suggests TLR4 agonism to prevent metastasis and promote survival in experimental metastasis models...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27899893/raynaud-s-phenomenon-a-brief-review-of-the-underlying-mechanisms
#2
REVIEW
Manal M Fardoun, Joseph Nassif, Khodr Issa, Elias Baydoun, Ali H Eid
Raynaud's phenomenon (RP) is characterized by exaggerated cold-induced vasoconstriction. This augmented vasoconstriction occurs by virtue of a reflex response to cooling via the sympathetic nervous system as well as by local activation of α2C adrenoceptors (α2C-AR). In a cold-initiated, mitochondrion-mediated mechanism involving reactive oxygen species and the Rho/ROCK pathway, cytoskeletal rearrangement in vascular smooth muscle cells orchestrates the translocation of α2C-AR to the cell membrane, where this receptor readily interacts with its ligand...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27899892/age-dependent-hepatic-udp-glucuronosyltransferase-gene-expression-and-activity-in-children
#3
Elizabeth Neumann, Huma Mehboob, Jacqueline Ramírez, Snezana Mirkov, Min Zhang, Wanqing Liu
UDP-glucuronosyltransferases (UGTs) are important phase II drug metabolism enzymes. The aim of this study was to explore the relationship between age and changes in mRNA expression and activity of major human hepatic UGTs, as well as to understand the potential regulatory mechanism underlying this relationship. Using previously generated data, we investigated age-dependent mRNA expression levels of 11 hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17) and 16 transcription factors (AHR, AR, CAR, ESR2, FXR, GCCR, HNF1a, HNF3a, HNF3b, HNF4a, PPARA, PPARG, PPARGC, PXR, SP1, and STAT3) in liver tissue of donors (n = 38) ranging from 0 to 25 years of age...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27899891/cardiac-stat3-deficiency-impairs-contractility-and-metabolic-homeostasis-in-hypertension
#4
Raffaele Altara, Romain Harmancey, Sean P Didion, George W Booz, Fouad A Zouein
Signal transducer and activator of transcription 3 (STAT3) protects the heart from acute ischemic stress. However, the importance of STAT3 to the heart in chronic stress, such as hypertension, is not known. To study this, we used cardiomyocyte-targeted STAT3 knockout (KO) mice and Angiotensin II (ANG II) infusion by osmotic minipumps. After 4 weeks, ANG II induced similar cardiac hypertrophy in wild type (WT) and cardiac Cre-expressing control (CTRL) mice with no impairment of cardiac function. In contrast, STAT3 KO mice exhibited reduced contractile function but similar hypertrophy to CTRL mice...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27895586/weakening-impact-of-excessive-human-serum-albumin-ehsa-on-cisplatin-and-etoposide-anticancer-effect-in-c57bl-6-mice-with-tumor-and-in-human-nsclc-a549-cells
#5
Zhen Yang, Ting Zhou, Yuanchi Cheng, Mingming Li, Xianglin Tan, Feng Xu
Excessive human serum albumin (eHSA) impact on anticancer effects is inconsistent. We explored the outcome of cisplatin (DDP)/etoposide (VP-16) plus eHSA in vivo and in vitro. C57BL/6 mice with tumor were used to compare the efficacy of DDP/VP-16 alone and DDP/VP-16+eHSA. Blood albumin was measured to confirm whether eHSA elevate its level. Western blotting assay were used to measure the expression of ERCC1/TOP2A in tumor tissues. Cell proliferation, mRNA, and protein expression of ERCC1/TOP2A were also assayed to compare two groups in A549 cells...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27895585/feto-maternal-trafficking-of-exosomes-in-murine-pregnancy-models
#6
Samantha Sheller-Miller, Jun Lei, George Saade, Carlos Salomon, Irina Burd, Ramkumar Menon
Timing and initiation of labor are well-orchestrated by signals communicated between the fetal and maternal compartments; however, how these signals are communicated is not completely understood. Fetal exosomes, intercellular signaling vesicles, may play a key role in the process. The objective of this study was to evaluate exosome trafficking in vivo from fetal to maternal compartments. Pregnant CD-1 mice were intra-amniotically injected on gestational day 16 and 17 with exosomes isolated from primary human amnion epithelial cells fluorescently labeled with the lipophilic dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27895584/induced-pluripotent-stem-cells-inhibit-bleomycin-induced-pulmonary-fibrosis-in-mice-through-suppressing-tgf-%C3%AE-1-smad-mediated-epithelial-to-mesenchymal-transition
#7
Yan Zhou, Zhong He, Yuan Gao, Rui Zheng, Xiaoye Zhang, Li Zhao, Mingqi Tan
Pulmonary fibrosis is a progressive and irreversible fibrotic lung disorder with high mortality and few treatment options. Recently, induced pluripotent stem (iPS) cells have been considered as an ideal resource for stem cell-based therapy. Although, an earlier study demonstrated the therapeutic effect of iPS cells on pulmonary fibrosis, the exact mechanisms remain obscure. The present study investigated the effects of iPS cells on inflammatory responses, transforming growth factor (TGF)-β1 signaling pathway, and epithelial to mesenchymal transition (EMT) during bleomycin (BLM)-induced lung fibrosis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27895583/matching-adherence-interventions-to-patient-determinants-using-the-theoretical-domains-framework
#8
REVIEW
Samuel S Allemann, Robby Nieuwlaat, Bart J F van den Bemt, Kurt E Hersberger, Isabelle Arnet
Introduction: Despite much research, interventions to improve medication adherence report disappointing and inconsistent results. Tailored approaches that match interventions and patient determinants of non-adherence were seldom used in clinical trials. The presence of a multitude of theoretical frameworks and models to categorize interventions and patient determinants complicated the development of common categories shared by interventions and determinants. We retrieved potential interventions and patient determinants from published literature on medication adherence, matched them like locks and keys, and categorized them according to the Theoretical Domains Framework (TDF)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27895582/introduction-of-an-n-glycosylation-site-into-udp-glucuronosyltransferase-2b3-alters-its-sensitivity-to-cytochrome-p450-3a1-dependent-modulation
#9
Tatsuro Nakamura, Naho Yamaguchi, Yuu Miyauchi, Tomoki Takeda, Yasushi Yamazoe, Kiyoshi Nagata, Peter I Mackenzie, Hideyuki Yamada, Yuji Ishii
Our previous studies have demonstrated functional protein-protein interactions between cytochrome P450 (CYP) 3A and UDP-glucuronosyltransferase (UGT). However, the role of carbohydrate chains of UGTs in the interaction with CYP is not well understood. To address this issue, we examined whether CYP3A1 modulates the function of UGT2B3 which lacks potential glycosylation sites. We also examined whether the introduction of N-glycosylation to UGT2B3 affects CYP3A-dependent modulation of UGT function. To introduce a potential glycosylation site into UGT2B3, Ser 316 of UGT2B3 was substituted with Asn by site-directed mutagenesis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27895581/evaluation-of-near-infrared-dyes-as-markers-of-p-glycoprotein-activity-in-tumors
#10
Inessa Semenenko, Emma Portnoy, Mohammed Aboukaoud, Serge Guzy, Miriam Shmuel, Gal Itzhak, Sara Eyal
Aim: The multidrug resistance protein 1 (MDR1; P-glycoprotein) has been associated with efflux of chemotherapeutic agents from tumor cells and with poor patient prognosis. This study evaluated the feasibility of non-invasive, non-radioactive near infrared (NIR) imaging methodology for detection of MDR1 functional activity in tumors. Methods: Initial accumulation assays were conducted in MDR1-overexpressing MDCK cells (MDCK-MDR1) and control MDCK cells (MDCK-CT) using the NIR dyes indocyanine green (ICG), IR-783, IR-775, rhodamine 800, XenoLight DiR, and Genhance 750, at 0...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27895580/increased-levels-of-mirna-146a-in-serum-and-histologic-samples-of-patients-with-uveal-melanoma
#11
Andrea Russo, Rosario Caltabiano, Antonio Longo, Teresio Avitabile, Livio M Franco, Vincenza Bonfiglio, Lidia Puzzo, Michele Reibaldi
Purpose: To analyze MiRs expression in serum of UM patients, respect to healthy donors, and to compare this data with MiRs expressed in formalin-fixed, paraffin-embedded UM samples. Methods: Expression profile of 754 miRNAs was performed in serum of patients with uveal melanoma who underwent primary enucleation. The level of miRNAs increased in serum was individually analyzed on FFPE UM samples and compared to choroidal melanocytes from unaffected eyes. Results: Fourteen patients with uveal melanoma were included in the study...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27895579/pharmacodynamic-modeling-of-cell-cycle-effects-for-gemcitabine-and-trabectedin-combinations-in-pancreatic-cancer-cells
#12
Xin Miao, Gilbert Koch, Sihem Ait-Oudhia, Robert M Straubinger, William J Jusko
Combinations of gemcitabine and trabectedin exert modest synergistic cytotoxic effects on two pancreatic cancer cell lines. Here, systems pharmacodynamic (PD) models that integrate cellular response data and extend a prototype model framework were developed to characterize dynamic changes in cell cycle phases of cancer cell subpopulations in response to gemcitabine and trabectedin as single agents and in combination. Extensive experimental data were obtained for two pancreatic cancer cell lines (MiaPaCa-2 and BxPC-3), including cell proliferation rates over 0-120 h of drug exposure, and the fraction of cells in different cell cycle phases or apoptosis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27891094/anti-acne-activity-of-italian-medicinal-plants-used-for-skin-infection
#13
Kate Nelson, James T Lyles, Tracy Li, Alessandro Saitta, Eugenia Addie-Noye, Paula Tyler, Cassandra L Quave
Propionibacterium acnes is implicated in the pathogenesis of acne vulgaris, which impacts >85% of teenagers. Novel therapies are in high demand and an ethnopharmacological approach to discovering new plant sources of anti-acne therapeutics could contribute to filling this void in effective therapies. The aims of our study were two-fold: (1) To determine if species identified in ethnopharmacological field studies as having traditional uses for skin and soft tissue infection (SSTI) exhibit significantly more activity against P...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27891093/targeting-strategies-for-renal-cell-carcinoma-from-renal-cancer-cells-to-renal-cancer-stem-cells
#14
REVIEW
Zhi-Xiang Yuan, Jingxin Mo, Guixian Zhao, Gang Shu, Hua-Lin Fu, Wei Zhao
Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rationale for therapies targeting this aggressive cell population...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27891092/dihydrotanshinone-i-attenuates-atherosclerosis-in-apoe-deficient-mice-role-of-nox4-nf-%C3%AE%C2%BAb-mediated-lectin-like-oxidized-ldl-receptor-1-lox-1-of-the-endothelium
#15
Wenwen Zhao, Chunxia Li, Hongwei Gao, Qin Wu, Jingshan Shi, Xiuping Chen
Dihydrotanshinone I (DHT) is a natural compound extracted from Salvia miltiorrhiza Bunge which has been widely used for treating cardiovascular diseases. However, its role in atherosclerosis remains unclear. In this study, the effect of DHT on atherosclerosis were investigated using apolipoprotein E-deficient (ApoE(-/-)) mice and endothelial cells. In lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), DHT (10 nM) decreased lectin-like ox-LDL receptor-1 (LOX-1) and NADPH oxidase 4 (NOX4) expression, reactive oxygen species (ROS) production, NF-κB nuclear translocation, ox-LDL endocytosis and monocytes adhesion...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27881964/corrigendum-bioassay-guided-isolation-of-sesquiterpene-coumarins-from-ferula-narthex-bioss-a-new-anticancer-agent
#16
Mahboob Alam, Ajmal Khan, Abdul Wadood, Ayesha Khan, Shumaila Bashir, Akhtar Aman, Abdul Khaliq Jan, Abdur Rauf, Bashir Ahmad, Abdur Rahman Khan, Umar Farooq
[This corrects the article on p. 26 in vol. 7, PMID: 26909039.].
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27881963/angiogenesis-inhibitors-for-the-treatment-of-hepatocellular-carcinoma
#17
REVIEW
Massimiliano Berretta, Luca Rinaldi, Fabrizio Di Benedetto, Arben Lleshi, Vallì De Re, Gaetano Facchini, Paolo De Paoli, Raffaele Di Francia
Background: Angiogenesis inhibitors have become an important therapeutic approach in the treatment of hepatocellular carcinoma (HCC) patients. The therapeutic inhibition of angiogenesis of Sorafenib in increasing overall survival of patients with HCC is a fundamental element of the treatment of this disease. Considering the heterogeneous aspects of HCC and to boost therapeutic efficacy, prevail over drug resistance and lessen toxicity, adding antiangiogenic drugs to antiblastic chemotherapy (AC), radiation therapy or other targeted drugs have been evaluated...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27881962/cigarette-smoking-induced-cardiac-hypertrophy-vascular-inflammation-and-injury-are-attenuated-by-antioxidant-supplementation-in-an-animal-model
#18
Moustafa Al Hariri, Kazem Zibara, Wissam Farhat, Yasmine Hashem, Nadia Soudani, Farah Al Ibrahim, Eva Hamade, Asad Zeidan, Ahmad Husari, Firas Kobeissy
Background: Cardiovascular diseases are the leading causes of morbidity and mortality worldwide. Cigarette smoking remains a global health epidemic with associated detrimental effects on the cardiovascular system. In this work, we investigated the effects of cigarette smoke exposure on cardiovascular system in an animal model. The study then evaluated the effects of antioxidants (AO), represented by pomegranate juice, on cigarette smoke induced cardiovascular injury. This study aims at evaluating the effect of pomegranate juice supplementation on the cardiovascular system of an experimental rat model of smoke exposure...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27877130/cannabidiol-as-a-potential-new-type-of-an-antipsychotic-a-critical-review-of-the-evidence
#19
REVIEW
Cathrin Rohleder, Juliane K Müller, Bettina Lange, F M Leweke
There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ(9)-THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27877129/curcumin-inhibits-transforming-growth-factor-%C3%AE-induced-differentiation-of-mouse-lung-fibroblasts-to-myofibroblasts
#20
Daishun Liu, Ling Gong, Honglan Zhu, Shenglan Pu, Yang Wu, Wei Zhang, Guichuan Huang
Transforming growth factor β (TGF-β) induced differentiation of lung fibroblasts to myofibroblasts is a key event in the pathogenesis of pulmonary fibrosis. This study aimed to evaluate the effect of curcumin on TGF-β induced differentiation of lung fibroblasts to myofibroblasts and explore the underlying mechanism. Mouse lung fibroblasts were cultured and treated with TGF-β2 and curcumin or rosiglitazone. Cell vitality was examined by MTT assay. The secretion of collagen-1 was assessed by ELISA. α smooth muscle actin (α-SMA) was visualized by immunofluorescence technique...
2016: Frontiers in Pharmacology
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