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Frontiers in Pharmacology

Benjamin Rémy, Sonia Mion, Laure Plener, Mikael Elias, Eric Chabrière, David Daudé
Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS) to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs), as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria...
2018: Frontiers in Pharmacology
Jian Li, Mengyang Liu, Haiyang Yu, Wei Wang, Lifeng Han, Qian Chen, Jingya Ruan, Shaoshi Wen, Yi Zhang, Tao Wang
Objective: Mangiferin (MGF) is a natural xanthone, with regulation effect on lipid metabolism. However, the molecular mechanism remains unclear. We purposed after oral administration, MGF is converted to its active metabolite(s), which contributes to the effects on lipid metabolism. Methods: KK-Ay mice were used to validate the effects of MGF on lipid metabolic disorders. Liver biochemical indices and gene expressions were determined. MGF metabolites were isolated from MGF administrated rat urine. Mechanism studies were carried out using HepG2 cells treated by MGF and its metabolite with or without inhibitors or small interfering RNA (siRNA)...
2018: Frontiers in Pharmacology
Hozeifa M Hassan, Bashir A Yousef, Hongli Guo, Liu Xiaoxin, Luyong Zhang, Zhenzhou Jiang
Tuberculosis (TB) is one of the oldest infectious diseases that affected humankind and remains one of the world's deadliest communicable diseases that could be considered as global emergency, but the discovery and development of isoniazid (INH) in the 1950s paved the way to an effective single and/or combined first-line anti-TB therapy. However, administration of INH induces severe hepatic toxicity in some patients. Previously, we establish a rat model of INH hepatotoxicity utilizing the inflammatory stress theory, in which bacterial lipopolysaccharide (LPS) potentially enhanced INH toxicity...
2018: Frontiers in Pharmacology
Yang Q Xia, Ren J Hua, Chen Juan, Zhou H Zhong, Cheng S Tao, Ren Fang, He Lin, Gong Rui, Chen Yong
Multidrug resistance (MDR) due to overexpression of MDR1 is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). In this study, we explored the function and underlying molecular mechanism of SIRT6 in MDR of HCC. Chemotherapeutic agents (doxorubicin, cisplatin, and sorafenib) treatment increased SIRT6 mRNA and protein level in two HCC cell lines in a dose-dependent manner. SIRT6 depletion resulted in decreased cell viability and increased apoptosis in HCC cells treated with chemotherapeutic agents...
2018: Frontiers in Pharmacology
Mariana Alves, Edward Beamer, Tobias Engel
Epilepsy encompasses a heterogeneous group of neurological syndromes which are characterized by recurrent seizures affecting over 60 million people worldwide. Current anti-epileptic drugs (AEDs) are mainly designed to target ion channels and/or GABA or glutamate receptors. Despite recent advances in drug development, however, pharmacoresistance in epilepsy remains as high as 30%, suggesting the need for the development of new AEDs with a non-classical mechanism of action. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype...
2018: Frontiers in Pharmacology
Xuechan Lyu, Jiang Du, Guilai Zhan, Yujie Wu, Hang Su, Youwei Zhu, Fredrik Jarskog, Min Zhao, Xiaoduo Fan
Objective: The rates of obesity and cigarette smoking are much higher in patients with schizophrenia compared to the general population. This study was to examine whether naltrexone and bupropion combination treatment can help weight loss and smoking cessation in patients with schizophrenia. Methods: Obese male schizophrenia patients with current cigarette smoking were randomized to receive adjunctive naltrexone (25 mg/day) and bupropion (300 mg/day) combination or placebo for 24 weeks. Twenty-two patients were enrolled in the study, and 21 patients completed the study (11 in the treatment group, and 10 in the placebo group)...
2018: Frontiers in Pharmacology
Irena Svobodova, Anirban Bhattaracharya, Milorad Ivetic, Zdenka Bendova, Hana Zemkova
The circadian rhythms in physiological and behavioral functions are driven by a pacemaker located in the suprachiasmatic nucleus (SCN). The rhythms continue in constant darkness and depend on cell-cell communication between neurons and glia. The SCN astrocytes generate also a circadian rhythm in extracellular adenosine 5'-triphosphate (ATP) accumulation, but molecular mechanisms that regulate ATP release are poorly understood. Here, we tested the hypothesis that ATP is released via the plasma membrane purinergic P2X7 receptors (P2X7Rs) and P2Y receptors (P2YRs) which have been previously shown to be expressed in the SCN tissue at transcriptional level...
2018: Frontiers in Pharmacology
Li Liu, Mingxing Miao, Yang Chen, Zhongjian Wang, Binbin Sun, Xiaodong Liu
This study investigated alterations in the function and expression of P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) at the blood-brain barrier (BBB) of acute liver failure (ALF) mice and its clinical significance. ALF mice were developed using intraperitoneal injection of thioacetamide. P-GP, BCRP, and MRP2 functions were determined by measuring the ratios of brain-to-plasma concentration of rhodamine 123, prazosin, and dinitrophenyl- S -glutathione, respectively...
2018: Frontiers in Pharmacology
Gan Wang, Chengbo Long, Weihui Liu, Cheng Xu, Min Zhang, Qiong Li, Qiumin Lu, Ping Meng, Dongsheng Li, Mingqiang Rong, Zhaohui Sun, Xiaodong Luo, Ren Lai
Considering blood-sucking habits of leeches from surviving strategy of view, it can be hypothesized that leech saliva has analgesia or anesthesia functions for leeches to stay undetected by the host. However, no specific substance with analgesic function has been reported from leech saliva although clinical applications strongly indicated that leech therapy produces a strong and long lasting pain-reducing effect. Herein, a novel family of small peptides (HSTXs) including 11 members which show low similarity with known peptides was identified from salivary glands of the leech Haemadipsa sylvestris ...
2018: Frontiers in Pharmacology
Laura Hidalgo-Garcia, Julio Galvez, M Elena Rodriguez-Cabezas, Per O Anderson
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract characterized by an exacerbated mucosal immune response. Macrophages play pivotal roles in the maintenance of gut homeostasis but they are also implicated in the pathogenesis of IBD. They are highly plastic cells and their activation state depends on the local environment. In the healthy intestine, resident macrophages display an M2 phenotype characterized by inflammatory energy, while inflammatory M1 macrophages dominate in the inflamed intestinal mucosa...
2018: Frontiers in Pharmacology
Alan L Pehrson, Christian S Pedersen, Kirstine Sloth Tølbøl, Connie Sanchez
Major depressive disorder (MDD) is associated with cognitive impairments that may contribute to poor functional outcomes. Clinical data suggests that the multimodal antidepressant vortioxetine attenuates some cognitive impairments in MDD patients, but the mechanistic basis for these improvements is unclear. One theory suggests that vortioxetine improves cognition by suppressing γ-amino butyric acid (GABA)ergic neurotransmission, thereby increasing glutamatergic activation. Vortioxetine's effects on cognition, GABA and glutamate neurotransmission have been supported in separate experiments, but no empirical work has directly connected vortioxetine's cognitive effects to those on GABA and glutamate neurotransmission...
2018: Frontiers in Pharmacology
Chien-Liang Fang, Yiwei Wang, Kevin H-Y Tsai, Hsin-I Chang
The dermis of human skin contains large numbers of fibroblasts that are responsible for the production of the extracellular matrix (ECM) that supporting skin integrity, elasticity and wound healing. Previously, an in vivo study demonstrated that dermal fibroblasts siting in the lower dermis are capable to convert into skin adipose layer and hence fibroblast lipogenesis may vary the structure and elasticity of dermis. In the present study, Hs68 human dermal fibroblasts were utilized as an in vitro model to study the lipogenesis via using adipogenic differentiation medium (ADM)...
2018: Frontiers in Pharmacology
Marilia N N Lima, Cleber C Melo-Filho, Gustavo C Cassiano, Bruno J Neves, Vinicius M Alves, Rodolpho C Braga, Pedro V L Cravo, Eugene N Muratov, Juliana Calit, Daniel Y Bargieri, Fabio T M Costa, Carolina H Andrade
Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium , affecting more than 200 million people worldwide every year and leading to about a half million deaths. Malaria parasites of humans have evolved resistance to all current antimalarial drugs, urging for the discovery of new effective compounds. Given that the inhibition of deoxyuridine triphosphatase of Plasmodium falciparum ( Pf dUTPase) induces wrong insertions in plasmodial DNA and consequently leading the parasite to death, this enzyme is considered an attractive antimalarial drug target...
2018: Frontiers in Pharmacology
Ruslan Masgutov, Galina Masgutova, Liliya Mukhametova, Ekaterina Garanina, Svetlana S Arkhipova, Elena Zakirova, Yana O Mukhamedshina, Zhuravleva Margarita, Zarema Gilazieva, Valeriia Syromiatnikova, Adelya Mullakhmetova, Gulnaz Kadyrova, Mariya Nigmetzyanova, Sergeev Mikhail, Pankov Igor, Ramil Yagudin, Albert Rizvanov
We examined the effect of transplantation of allogenic adipose-derived stem cells (ADSCs) with properties of mesenchymal stem cells (MSCs) on posttraumatic sciatic nerve regeneration in rats. We suggested an approach to rat sciatic nerve reconstruction using the nerve from the other leg as a graft. The comparison was that of a critical 10 mm nerve defect repaired by means of autologous nerve grafting versus an identical lesion on the contralateral side. In this experimental model, the same animal acts simultaneously as a test model, and control...
2018: Frontiers in Pharmacology
Hui Cao, Senlin Li, Rui Xie, Na Xu, Ying Qian, Hongdan Chen, Qinyu Hu, Yihong Quan, Zhihong Yu, Junjun Liu, Ming Xiang
Dangguiliuhuang decoction (DGLHD) has been demonstrated to be effective in treating inflammatory, hepatic steatosis, and insulin resistance. In the study, we tried to elucidate the pharmacological efficacy and mechanism of DGLHD against liver fibrosis and predicate potential active ingredients and targets via network analysis and experimental validation. In the formula, we totally discovered 76 potential active ingredients like baicalein, berberine, and wogonin, and 286 corresponding targets including PTGS (prostaglandin-endoperoxide synthase) 2, PPAR (peroxisome proliferator-activated receptors) -γ, and NF-κB (nuclear factor-κB)...
2018: Frontiers in Pharmacology
Yifan Wang, Weiye Deng, Nan Li, Shinya Neri, Amrish Sharma, Wen Jiang, Steven H Lin
Since the approval of anti-CTLA4 therapy (ipilimumab) for late-stage melanoma in 2011, the development of anticancer immunotherapy agents has thrived. The success of many immune-checkpoint inhibitors has drastically changed the landscape of cancer treatment. For some types of cancer, monotherapy for targeting immune checkpoint pathways has proven more effective than traditional therapies, and combining immunotherapy with current treatment strategies may yield even better outcomes. Numerous preclinical studies have suggested that combining immunotherapy with radiotherapy could be a promising strategy for synergistic enhancement of treatment efficacy...
2018: Frontiers in Pharmacology
Yassine Bouatou, Ludwig Stenz, Belen Ponte, Serge Ferrari, Ariane Paoloni-Giacobino, Karine Hadaya
Background: Corticosteroids are associated with reduced bone mineral density (BMD), as well as water and salt retention, leading to hypertension. They are substrates for P-glycoprotein, a protein coded by the highly polymorphic ABCB1 gene. We hypothesized that one ABCB1 polymorphism, rs1045642, is associated with blood pressure and BMD parameters at 1-year post kidney transplantation (KT). Methods: Rs1045642 was genotyped using pyrosequencing in 40 KT recipients. Both dominant (CC vs. CT + TT) and codominant (CC vs...
2018: Frontiers in Pharmacology
Vincenzo Sorrenti, Gabriella Contarini, Stefania Sut, Stefano Dall'Acqua, Francesca Confortin, Andrea Pagetta, Pietro Giusti, Morena Zusso
Systemic lipopolysaccharide (LPS) induces an acute inflammatory response in the central nervous system (CNS) ("neuroinflammation") characterized by altered functions of microglial cells, the major resident immune cells of the CNS, and an increased inflammatory profile that can result in long-term neuronal cell damage and severe behavioral and cognitive consequences. Curcumin, a natural compound, exerts CNS anti-inflammatory and neuroprotective functions mainly after chronic treatment. However, its effect after acute treatment has not been well investigated...
2018: Frontiers in Pharmacology
Ge Li-Sha, Liu Li, Zhou De-Pu, Shi Zhe-Wei, Gu Xiaohong, Chen Guang-Yi, Li Jia, Lin Jia-Feng, Chu Maoping, Li Yue-Chun
This study was designed to explore the effects of ivabradine on cardiomyocyte apoptosis in a murine model of chronic viral myocarditis (CVMC). Mice were inoculated intraperitoneally with Coxsackievirus B3 at days 1, 14, and 28, respectively. On day 42, the mice were gavaged with ivabradine for 30 days until the 72nd day. The heart of infected mice was dilated and a large number of interstitial fibroblasts infiltrated into the myocardium on day 42. Compared with the untreated CVMC mice, mice treated with ivabradine showed a significant reduction in heart rate and less impairment of left ventricular function on day 72...
2018: Frontiers in Pharmacology
Frédérique Rodieux, Laszlo Vutskits, Klara M Posfay-Barbe, Walid Habre, Valérie Piguet, Jules A Desmeules, Caroline F Samer
Children represent a vulnerable population in which management of nociceptive pain is complex. Drug responses in children differ from adults due to age-related differences. Moreover, therapeutic choices are limited by the lack of indication for a number of analgesic drugs due to the challenge of conducting clinical trials in children. Furthermore the assessment of efficacy as well as tolerance may be complicated by children's inability to communicate properly. According to the World Health Organization, weak opioids such as tramadol and codeine, may be used in addition to paracetamol and ibuprofen for moderate nociceptive pain in both children and adults...
2018: Frontiers in Pharmacology
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