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Drug Design, Development and Therapy

Yu-Jin Tang, Kai Li, Cheng-Liang Yang, Ke Huang, Jing Zhou, Yu Shi, Ke-Gong Xie, Jia Liu
Background: Spinal cord injury (SCI) is a disease of the central nervous system with few restorative treatments. Autophagy has been regarded as a promising therapeutic target for SCI. The inhibitor of phosphatase and tensin homolog deleted on chromosome ten (PTEN) bisperoxovanadium (bpV[pic]) had been claimed to provide a neuroprotective effect on SCI; but the underlying mechanism is still not fully understood. Materials and methods: Acute SCI model were generated with SD Rats and were treated with control, acellular spinal cord scaffolds (ASC) obtained from normal rats, bpV(pic), and combined material of ASC and bpV(pic)...
2019: Drug Design, Development and Therapy
Muhammad Faisal, Willi Cawello, Bjoern B Burckhardt, Stephanie Laer
Introduction: Comparative pharmacokinetic (PK) data analysis of drugs administered using developed child-appropriate and market authorized dosage formulation is sparse and is important in pediatric drug development. Objectives: To compare and evaluate any differences in PK of enalapril administered using two treatments of child-appropriate orodispersible minitablets (ODMTs) and market authorized reference tablet formulation (Renitec® ) using PK compartment model and validated least square minimization method (LSMM) of parameter estimation...
2019: Drug Design, Development and Therapy
Vincenzo Spagnuolo, Laura Galli, Andrea Poli, Alba Bigoloni, Luca Fumagalli, Nicola Gianotti, Silvia Nozza, Davide Ferrari, Massimo Locatelli, Adriano Lazzarin, Antonella Castagna
No abstract text is available yet for this article.
2019: Drug Design, Development and Therapy
Shiyu Gao, Jianwei Lin, Tianqi Wang, Yan Shen, Yan Li, Wenyu Yang, Kailiang Zhou, Haiyan Hu
Background: Qingxin kaiqiao fang (QKF) has been found to treat Alzheimer's disease (AD) through apoptosis inhibition. The mitogen-activated protein kinase (MAPK) pathway is closely related to apoptosis in the course of AD. This study aimed to investigate whether QKF-induced apoptosis depression is achieved through MAPK pathway. Materials and methods: C57BL/6 J and APP/PS1 mice were used as control and model groups. APP/PS1 mice were treated with different dosages of QKF (4...
2019: Drug Design, Development and Therapy
Yuzhang Liu, Qiang Du, Chengbang Ma, Xinping Xi, Lei Wang, Mei Zhou, James F Burrows, Tianbao Chen, Hui Wang
Background: Antimicrobial peptides (AMPs) from the skin secretions of amphibians are now considered as a potential alternative to conventional antibiotics. Phylloseptins are a family of AMPs identified in the skin secretions of Phyllomedusinae tree frogs which exhibit highly conserved structural characteristics. This study examines the structure-activity relationship of the newly discovered phylloseptin, Phylloseptin-PHa (PSPHa) from Pithecopus hypochondrialis . Materials and methods: PSPHa and modified analogs were produced by solid phase synthesis and purified by reverse-phase HPLC...
2019: Drug Design, Development and Therapy
Hui Zeng, Jiaping Zheng, Song Wen, Jun Luo, Guoliang Shao, Yongjun Zhang
Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide, however, the prognosis for HCC remains unsatisfactory. This study aimed to explore the role of miR-339-5p in HCC. Methods: We first used quantitative real-time PCR to examine the level of miR-339-5p in HCC tissues. Then we further adopted Western blotting assay, CCK8, cell invasion assays, apoptosis detection assay, and luciferase assay to analyze how it mediate the development of HCC...
2019: Drug Design, Development and Therapy
Buthina Abdallah Al-Oudat, Mohammad Ali Alqudah, Suaad Abdallah Audat, Qosay Ali Al-Balas, Tamam El-Elimat, Mohammad Abdelhafeez Hassan, Islam Nawaf Frhat, Marwah Mohammad Azaizeh
Background: Chrysin (5,7-dihydroxyflavone) is a widely distributed natural flavonoid found in many plant extracts, honey and propolis. Several studies revealed that chrysin possesses multiple biological activities including anti-cancer effects. It has been established that activation of apoptosis is the key molecular mechanism responsible for the cytotoxic potential of chrysin. The objective of this study was to design and synthesize potent chrysin analogues as potential cytotoxic agents...
2019: Drug Design, Development and Therapy
Dao-Kui Xia, Zhi-Gang Hu, Yu-Feng Tian, Fan-Jun Zeng
Background: Previous clinical studies reported inconsistent results on the associations of statins with the mortality and survival of lung cancer patients. This review and meta-analysis summarized the impact of statins on mortality and survival of lung cancer patients. Materials and methods: Eligible papers of this meta-analysis were searched by using PubMed, EMBASE, and Cochrane until July 2017. Primary end points were the mortality (all-cause mortality and cancer-specific mortality) and survival (progression-free survival and overall survival) of patients with statin use...
2019: Drug Design, Development and Therapy
Chi-Chun Huang, Hsin-Yi Chen, Ruei-Hsin Chang, Pen-An Liao, Heng-Hui Lien, Chih-Sheng Hung, Sien-Sing Yang, Jui-Ting Hu
Background: Sorafenib is an oral tyrosine kinase inhibitor that is indicated for advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine the clinical outcomes of HCC patients receiving sorafenib in real-life clinical setting in comparison with formal clinical trials. Methods: Patients diagnosed with advanced HCC between 2007 and 2015 at single institute were retrospectively enrolled and evaluated for survival and tolerability following sorafenib treatment...
2019: Drug Design, Development and Therapy
Kai Yao, Yong-Fei Zhao, Heng-Bing Zu
Purpose: As a novel antidepressant drug, agomelatine has good therapeutic effect on the mood disorder and insomnia in Alzheimer's disease (AD). Recent studies have shown the neuroprotective function of agomelatine, including anti-oxidative and anti-apoptosis effect. However, it remains unclear whether agomelatine exerts neuroprotection in AD. Thus, the neuroprotective effect of agomelatine against amyloid beta 25-35 (Aβ25-35 )-induced toxicity in PC12 cells was evaluated in this study...
2019: Drug Design, Development and Therapy
Qiuzhen Liang, Xinghua Song, Shengli She, Zhen Wang, Chong Wang, Dawei Jiang
Background: Low drug concentration in the tuberculosis (TB) lesion and bone defects or nonunion after debridement are two major problems that occur in the course of treating osteo-articular TB. Thus, the combination of drug-delivery system and bone tissue repair appears to be the most promising option for osteoarticular TB treatment. Materials and methods: Herein, we report a novel anti-TB dual delivery system based on rifapentine polylactic acid microspheres (RPMs) to treat infections, with the addition of adipose-derived mesenchymal stem cells (ASCs) seeded in hydroxyapatite/tricalcium phosphate (HA/TCP) to promote bone formation...
2019: Drug Design, Development and Therapy
Junbei Wu, Yunhong Lu, Xiaofei Cao
Background: Percutaneous radiofrequency ablation (RFA) is a recently introduced alternative technique for the treatment of hepatic cancer. Anesthesia is required for RFA of hepatic cancer to achieve patient comfort and immobilization during this painful procedure. The purpose of this study was to investigate the analgesic efficacy and evaluate the safety of a single intravenous injection of oxycodone hydrochloride for this procedure. Patients and methods: A total of 120 American Society of Anesthesiologists class I-II grade patients for elective ultrasound-guided percutaneous RFA were enrolled in this randomized controlled trial...
2019: Drug Design, Development and Therapy
Denise Ms van Marion, Xu Hu, Deli Zhang, Femke Hoogstra-Berends, Jean-Paul G Seerden, Lizette Loen, Andre Heeres, Herman Steen, Robert H Henning, Bianca Jjm Brundel
Background: The heat shock protein (HSP) inducer, geranylgeranylacetone (GGA), was previously found to protect against atrial fibrillation (AF) remodeling in experimental model systems. Clinical application of GGA in AF is limited, due to low systemic concentrations owing to the hydrophobic character of GGA. Objectives: To identify novel HSP-inducing compounds, with improved physicochemical properties, that prevent contractile dysfunction in experimental model systems for AF...
2019: Drug Design, Development and Therapy
Vo Van Giau, Seong Soo A An, John Hulme
The worldwide misuse of antibiotics and the subsequent rise of multidrug-resistant pathogenic bacteria have prompted a paradigm shift in the established view of antibiotic and bacterial-human relations. The clinical failures of conventional antibiotic therapies are associated with lengthy detection methods, poor penetration at infection sites, disruption of indigenous microflora and high potential for mutational resistance. One of the most promising strategies to improve the efficacy of antibiotics is to complex them with micro or nano delivery materials...
2019: Drug Design, Development and Therapy
Hui Tong, Kai Zhao, Jingyu Zhang, Jinxin Zhu, Jianqi Xiao
Background: Y-box-binding protein-1 (YB-1) is aberrantly expressed in a variety of cancers. However, the biological functional role of YB-1 in glioma is not yet clear. Methods: The expression of MDM2 and YB-1 was analyzed by real time PCR. Overexpression and knockdown of YB-1 in glioma cells were created by transfection of pcDNA-YB-1 and siRNA against YB-1, respectively. Cell viability was performed by CCK8 assay. Results: Our findings showed that glioma tissues had higher expressions of YB-1 than that in cancer-free tissues in 54 glioma patients, which were also positively correlated with Murine MDM2 expression...
2019: Drug Design, Development and Therapy
Ricardo Costa, Saif Zaman, Susan Sharpe, Irene Helenowski, Colleen Shaw, Hyo Han, Hatem Soliman, Brian Czerniecki
Human epidermal growth factor receptor 2 (HER2)-targeted vaccines are under development, but have so far demonstrated only modest clinical efficacy. Additionally, there has been a lack of adequate safety assessment in large-scale prospective clinical trials. Therefore, we performed a meta-analysis of available clinical trial data to summarize the toxicity profiles of these treatments. Literature search was conducted in February 2018. The trials analyzed had at least one study arm consisting of HER2 vaccine monotherapy...
2019: Drug Design, Development and Therapy
Qingquan Wei, Rui Chen, Qiyang Lou, Jing Yu
Purpose: The purpose of this meta-analysis was to compare the efficacy and safety of corticosteroid implant and intravitreal ranibizumab for the treatment of macular edema (ME). Materials and methods: PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were comprehensively searched for studies comparing dexamethasone implant with ranibizumab in patients with ME. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and adverse events were extracted from the final eligible studies...
2019: Drug Design, Development and Therapy
Shiyu Mao, Junfeng Zhang, Yadong Guo, Ziwei Zhang, Yuan Wu, Wentao Zhang, Longsheng Wang, Jiang Geng, Yang Yan, Xudong Yao
Background: Immune checkpoint blockade targeting programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) signaling was approved recently for locally advanced and metastatic urothelial bladder carcinoma (UBC). Some patients experience a very rapid tumor progression, rather than clinical benefit, from anti-PD-L1/PD-1 therapy. Case presentation: A 58-year-old male diagnosed with non-muscle-invasive bladder cancer 3 years ago received transurethral resection of bladder tumor (TURBT) and intravesical chemotherapy...
2019: Drug Design, Development and Therapy
Haitao Ren, Yuan Li, Yan Chen, Liang Wang
Aim: To testify the hypothesis that endostatin exerts antifibrotic effects in hepatic stellate cells (HSCs) by modulating RhoA (ras homolog gene family, member A)/ROCK 1 (Rho-associated protein kinase 1) signal pathways. Materials and methods: HSCs-T6 of passages 3-5 were cultured in DMEM and serum starved for 48 hours. HSCs were grouped as follows: control group, TGF-β1 (transforming growth factor β1) group, endostatin+TGF-β1 group, PDGF-BB (platelet-derived growth factor-BB) group, and endostatin+PDGF-BB group...
2019: Drug Design, Development and Therapy
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