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Frontiers in Pharmacology

Hang Dong, Siyi Jiang, Yunfeng Fu, Yanwei Luo, Rong Gui, Jing Liu
Aim: To investigate the prognostic value of lncRNA NR_046683 in multiple myeloma (MM). Methods: High-throughput lncRNA array was combined with bioinformatics techniques to screen differentially expressed lncRNA in MM. qRT-PCR was adopted to determine the expression of target lncRNAs in MM patients and controls. Results: It was found for the first time that lncRNA NR_046683 is closely related to the prognosis of MM. It was also detected in tumor cell lines KM3, U266, especially in drug-resistant cell lines KM3/BTZ and MM1R...
2019: Frontiers in Pharmacology
Xiao Liu, Hong-Kui Yu, Li-Xian Gu, Jia-Kun Chen, Zhi-Bo Wen
Background and Objective: Intussusception is the most frequent pediatric abdominal emergency. Intestinal spasm, ischemia, necrosis and even death may occur without prompt diagnosis and treatment. The ultrasound-guided reduction by saline enema is a preferred non-surgical procedure for intussusception. Muscular relaxants can relieve the intestinal spasm and edema by relaxing the intestinal smooth muscle, which may facilitate the treatment of intussusception. However, controversy persists on whether muscular relaxants are effective in the procedure...
2019: Frontiers in Pharmacology
Chang Tu, Xiaojian Huang, Yifan Xiao, Mingyu Song, Yongzhuang Ma, Jiyuan Yan, Hongbo You, Hua Wu
Osteoarthritis (OA) is a common joint disease in the elderly population. Its development has been reported to be associated with cartilage degradation and inflammatory responses. Schisandrin A, a bioactive lignin in Schisandra sphenanthera , has shown its anti-inflammatory potential in various inflammation diseases. However, the effects of Schisandrin A on OA remain to explore. In this study, rat chondrocytes were treated with IL-1β (10 ng/ml) with or without different concentrations of Schisandrin A for 24 h...
2019: Frontiers in Pharmacology
Fang Bian, Xiao-Yan Yang, Gao Xu, Tao Zheng, Si Jin
The NLRP3 inflammasome, a multiprotein cytosolic complex that activates the IL-1 family of cytokines, plays an important role in atherosclerosis (AS). High-sensitivity c-reactive protein (hs-CRP) is widely recognized as a major cardiovascular risk predictor and recent studies name NLRP3 as a predictor of CRP levels. Mounting evidence has indicated that subendothelial retention of apolipoprotein B100-containing lipoproteins, such as low-density lipoprotein (LDL), is the initial step of atherogenesis, and is usually termed the "response to retention hypothesis...
2019: Frontiers in Pharmacology
Vincenzo Carafa, Lucia Altucci, Angela Nebbioso
Sirtuins (SIRTs), class III histone deacetylases, are differentially expressed in several human cancers, where they display both oncogenic and tumor-suppressive properties depending on cellular context and experimental conditions. SIRTs are involved in many important biological processes and play a critical role in cancer initiation, promotion, and progression. A growing body of evidence indicates the involvement of SIRTs in regulating three important tumor processes: epithelial-to-mesenchymal transition (EMT), invasion, and metastasis...
2019: Frontiers in Pharmacology
Kenji Hashimoto
Inflammation plays a key role in the pathogenesis of a number of psychiatric and neurological disorders. Soluble epoxide hydrolases (sEH), enzymes present in all living organisms, metabolize epoxy fatty acids (EpFAs) to corresponding 1,2-diols by the addition of a molecule of water. Accumulating evidence suggests that sEH in the metabolism of polyunsaturated fatty acids (PUFAs) plays a key role in inflammation. Preclinical studies demonstrated that protein expression of sEH in the prefrontal cortex, striatum, and hippocampus from mice with depression-like phenotype was higher than control mice...
2019: Frontiers in Pharmacology
Xuan Zeng, Weiwei Su, Yuying Zheng, Yudong He, Yan He, Hongyu Rao, Wei Peng, Hongliang Yao
Aging is an inevitable biological process characterized by the loss of functional capacity and associated with changes in all phases of pharmacokinetic processes. Naringin, a dietary flavanone glycoside, has been proved to be beneficial for the treatment of multiple age-associated chronic diseases. To date, the pharmacokinetic processes of naringin in aged individuals are still unknown. Thus, a rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QQQ-MS/MS) method was established for the determination of naringin and its metabolite naringenin in rat plasma, urine, feces, and tissue homogenate...
2019: Frontiers in Pharmacology
Ying Liu, Xia Zhang, Jingpu Zhang, Changqin Hu
Cephalosporins are beta-lactam antibiotics that are widely used in China. Five generations of cephalosporins have been introduced in clinical practice to date; moreover, some new candidates are also undergoing clinical evaluations. To improve the success rates of new drug development, we need to have a comprehensive understanding about the relationship between the structure of cephalosporins and the toxicity that it induces at an early stage. In the cephalosporins toxicity study using zebrafish, the drug absorption is a key point...
2019: Frontiers in Pharmacology
Daniel F Cruz, Carlos M Farinha, Agnieszka Swiatecka-Urban
Lemur Tyrosine Kinase 2 (LMTK2) is a recently cloned transmembrane protein, actually a serine/threonine kinase named after the Madagascar primate lemur due to the long intracellular C-terminal tail. LMTK2 is relatively little known, compared to other kinases but its role has been increasingly recognized. Published data show that LMTK2 regulates key cellular events, including endocytic trafficking, nerve growth factor signaling, apoptosis, and Cl- transport. Abnormalities in the expression and function of LMTK2 are associated with human disease, such as neurodegeneration, cancer and infertility...
2019: Frontiers in Pharmacology
Karl Kunzelmann, Jiraporn Ousingsawat, Inês Cabrita, Tereza Doušová, Andrea Bähr, Melanie Janda, Rainer Schreiber, Roberta Benedetto
The inflammatory airway disease cystic fibrosis (CF) is characterized by airway obstruction due to mucus hypersecretion, airway plugging, and bronchoconstriction. The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is dysfunctional in CF, leading to defects in epithelial transport. Although CF pathogenesis is still disputed, activation of alternative Cl- channels is assumed to improve lung function in CF. Two suitable non-CFTR Cl- channels are present in the airway epithelium, the Ca2+ activated channel TMEM16A and SLC26A9...
2019: Frontiers in Pharmacology
Bruno Laganà, Angelo Zullo, Maria Lia Scribano, Maria Sole Chimenti, Alberto Migliore, Andrea Picchianti Diamanti, Roberto Lorenzetti, Palma Scolieri, Lorenzo Ridola, Elena Ortona, Marina Pierdominici, Vincenzo Bruzzese
Spondyloarthritis (SpA) and inflammatory bowel diseases (IBD) are chronic inflammatory diseases characterized by an aberrant immune response and inflammation with a key role for TNF in their pathogenesis. Accordingly, TNF-inhibiting therapy (TNFi) has dramatically improved the management of these diseases. However, about 30% of patients discontinue TNFi for lack of response, loss of response, and side effects and/or adverse events. Thus, the possibility to identify in advance those patients who will have a good response to TNFi would be extremely beneficial...
2019: Frontiers in Pharmacology
Biljana Cvetanova, Ya-Ching Shen, Lie-Fen Shyur
Mutated proto-oncogene BRAF is a bona fide therapeutic target for melanomas. Regrettably, melanoma acquires resistance to BRAF inhibitors, e.g., vemurafenib (PLX4032) casting doubt on this promising melanoma targeted therapy. In this study, we explored the bioactivity of triterpenoid saponin cumingianoside A (CUMA), isolated from leaves and twigs of Dysoxylum cumingianum against PLX4032-resistant BRAFV 600E mutant melanoma A375-R in vitro and in vivo . Our data show that CUMA treatment inhibited A375-R melanoma cell proliferation in a time- and dose-dependent manner...
2019: Frontiers in Pharmacology
Ning-Ning Yuan, Cui-Zan Cai, Ming-Yue Wu, Qi Zhu, HuanXing Su, Min Li, JiaoYan Ren, Jie-Qiong Tan, Jia-Hong Lu
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of protein aggregates (namely Lewy bodies) in dopaminergic neurons in the substantia nigra region of the brain. Alpha-synuclein (α-syn) is the major component of Lewy bodies in PD patients, and impairment of the ubiquitin-proteasome system has been linked to its accumulation. In this work, we developed a tetracycline-inducible expression system, with simultaneous induced expression of α-syn-EGFP and a bright red fluorescent protein marker (mCherry) to screen for potential compounds for degrading α-syn...
2019: Frontiers in Pharmacology
Sara Redenšek, Dušan Flisar, Maja Kojović, Milica Gregorič Kramberger, Dejan Georgiev, Zvezdan Pirtošek, Maja Trošt, Vita Dolžan
Dopaminergic pathway is the most disrupted pathway in the pathogenesis of Parkinson's disease. Several studies reported associations of dopaminergic genes with the occurrence of adverse events of dopaminergic treatment. However, none of these studies adopted a pathway based approach. The aim of this study was to comprehensively evaluate the influence of selected single nucleotide polymorphisms of key dopaminergic pathway genes on the occurrence of motor and non-motor adverse events of dopaminergic treatment in Parkinson's disease...
2019: Frontiers in Pharmacology
Johan Georg Visser, Anton Du Preez Van Staden, Carine Smith
With the effectiveness of therapeutic agents ever decreasing and the increased incidence of multi-drug resistant pathogens, there is a clear need for administration of more potent, potentially more toxic, drugs. Alternatively, biopharmaceuticals may hold potential but require specialized protection from premature in vivo degradation. Thus, a paralleled need for specialized drug delivery systems has arisen. Although cell-mediated drug delivery is not a completely novel concept, the few applications described to date are not yet ready for in vivo application, for various reasons such as drug-induced carrier cell death, limited control over the site and timing of drug release and/or drug degradation by the host immune system...
2019: Frontiers in Pharmacology
Edyta Leyk, Marek Wesolowski
Hydroxypropyl methylcellulose (hypromellose) is a widely known excipient commonly used in the preparation of drug formulations. It can interact with some active pharmaceutical ingredients (APIs), thereby contributing to a reduction in crystallinity, serve as a solvent for API or form stable dispersion with no tendency to aggregation. The aim of the present study was to investigate the effect of hypromellose on the solubility, miscibility and amorphization of paracetamol in mixture with this polymer. Homogenized mixtures of paracetamol with hypromellose were studied using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier transform infrared (FT-IR) and Raman methods to obtain a deeper insight into the interactions between ingredients in solid state including phase diagram construction for crystalline API and amorphous polymer...
2019: Frontiers in Pharmacology
Xiaoting Tian, Fang Liu, Zhixiong Li, Yunfei Lin, Huan Liu, Pei Hu, Mingcang Chen, Zhaolin Sun, Zhou Xu, Yiting Zhang, Li Han, Yuanyuan Zhang, Guoyu Pan, Chenggang Huang
Objective: Inspired by the traditionally clinical application of herb pair Zhimu - Huangbo to treat diabetes, a combination of plant ingredients, timosaponin B2 (TB-2) and berberine (BBR), was evaluated for their anti-diabetic efficacy and cooperative mechanisms. Methods: The efficacy and pharmacokinetics of orally administered TB-2 (33.3 mg/kg/day), BBR (66.7 mg/kg/day), and TB-2+BBR (100 mg/kg/day) were evaluated in spontaneously non-obese diabetic Goto-Kakizaki (GK) rats, and metformin (200 mg/kg/day) was used as a positive control...
2019: Frontiers in Pharmacology
Yihua Yang, Zhe Wang, Ying Peng, Jinsong Ding, Wenhu Zhou
Micelles are highly attractive nano-drug delivery systems for targeted cancer therapy. While they have been demonstrated to significantly alleviate the side-effects of their cargo drugs, the therapy outcomes are usually suboptimal partially due to ineffective drug release and endosome entrapment. Stimulus-responsive nanoparticles have allowed controlled drug release in a smart fashion, and we want to use this concept to design novel micelles. Herein, we reported pH-sensitive paclitaxel (PTX)-loaded poly (ethylene glycol)-phenylhydrazone-dilaurate (PEG-BHyd-dC12 ) micelles (PEG-BHyd-dC12 /PTX)...
2019: Frontiers in Pharmacology
Hyunjun Park, Shinwoo Kang, Eunjoo Nam, Yoo-Hun Suh, Keun-A Chang
Polygala tenuifolia Willdenow is a herb known for its therapeutic effects in insomnia, depression, disorientation, and memory impairment. In Alzheimer's disease (AD) animal model, there has been no report on the effects of memory and cognitive impairment. PSM-04, an extract from the root of P. tenuifolia Willdenow, was developed with improved bioabsorption. The present study aimed to investigate the neuroprotective effects of PSM-04 on AD and reveal the possible molecular mechanism. The neuroprotective effect of PSM-04 in primary cortical neurons treated with L-glutamate, oligomeric Aβ, or H2 O2 ...
2019: Frontiers in Pharmacology
Francisco Ciruela, Kenneth A Jacobson
No abstract text is available yet for this article.
2019: Frontiers in Pharmacology
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