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targeted medicine

Jose Luis Lopez-Campos, Stefano Centanni
The study of airway diseases continues to present several challenges for modern medicine. The different disease presentations with variables and overlapping features may result in a real challenge for the clinician. In this context, the concept of precision medicine has started to emerge in order to give answers to some of these challenges from a diagnostic and therapeutic point of view. The main reasons to target for precision medicine in chronic obstructive pulmonary disease (COPD) include that there is variability in the clinical presentation, there is no correlation between the different clinical variables at the patient level, there are a number of relevant clinical variables associated with outcomes, we do have specific therapies for specific patient types, and that there is variability in the clinical response to different therapies...
March 20, 2018: COPD
Alexander N Orekhov, Igor A Sobenin
Atherosclerotic diseases are the leading cause of mortality in industrialized countries. Correspondingly, studying the pathogenesis of atherosclerosis and developing new methods of its diagnostic and treatment remain in the focus of current medicine and health care. This review aims to discuss the mechanistic role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in atherogenesis. In particular, the generally accepted hypothesis about the key role of oxidized LDL in atherogenesis is questioned, and an alternative concept of multiple modification of LDL is presented...
March 20, 2018: Current Medicinal Chemistry
Jenna L Gollihue, Samir P Patel, Alexander G Rabchevsky
Mitochondria are essential cellular organelles critical for generating adenosine triphosphate for cellular homeostasis, as well as various mechanisms that can lead to both necrosis and apoptosis. The field of "mitochondrial medicine" is emerging in which injury/disease states are targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. Consequently, novel mitochondrial transplantation strategies represent a potentially multifactorial therapy leading to increased adenosine triphosphate production, decreased oxidative stress, mitochondrial DNA replacement, improved bioenergetics and tissue sparing...
February 2018: Neural Regeneration Research
Peter J Turnbaugh
Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of specific genotypic or copy number variants in our "second genome" (the microbiome) has been largely overlooked. In this Perspective, I will discuss three major barriers to integrating metagenomics into pharmacology, highlighting ongoing research by us and others that has begun to shed light on the mechanisms that link the human microbiome to the efficacy and toxicity of small-molecule and biological therapies...
March 2018: MSystems
Xiangchun Li, Weiqi Xu, Wei Kang, Sunny H Wong, Mengyao Wang, Yong Zhou, Xiaodong Fang, Xiuqing Zhang, Huanming Yang, Chi H Wong, Ka F To, Stephen L Chan, Matthew T V Chan, Joseph J Y Sung, William K K Wu, Jun Yu
Objective: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with a dismal prognosis. However, driver genes and prognostic markers in HCC remain to be identified. It is hoped that in-depth analysis of HCC genomes in relation to available clinicopathological information will give rise to novel molecular prognostic markers. Methods: We collected genomic data of 1,061 HCC patients from previous studies, and performed integrative analysis to identify significantly mutated genes and molecular prognosticators...
2018: Theranostics
Xianhua Zhang, Linran Han, Jin Liu, Qiuyue Xu, Yuxin Guo, Wan Zheng, Jian Wang, Xi Huang, Ping Ren
In the present study, the pharmacokinetics of multi-components (naringenin, nobiletin, meranzin hydrate, narirutin, naringin, hesperidin, and neohesperidin) were investigated in acute depressive rats following oral administration of Fructus Aurantii (Zhi-Qiao, ZQ) extract (20 g/kg). A rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established to quantitatively or qualitatively analyze the 7 absorbed ingredients in the plasma, hippocampus and cortex of acute depressive rats...
2018: Frontiers in Pharmacology
Gordana Nikolić, Nikola M Stojanović, Pavle J Randjelović, Snežana Manojlović, Niko S Radulović
Utilization of herbal products (HPs) is a common practice in the traditional medicine of people from southeastern Serbia. In this study, we focused on the usage of HPs as a self-medication practice among patients diagnosed with a mental illness, by aiming to ascertain the usage prevalence, the identity of the main plant taxa utilized, their formulations and target symptoms. This was accomplished through a cross-sectional study of psychiatric outpatients, conducted in the Clinic for Mental Health Protection in Niš, and which included a questionnaire on HP utilization and a non-structured psychiatric interview...
March 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
M Urpi-Sarda, E Almanza-Aguilera, R Llorach, R Vázquez-Fresno, R Estruch, D Corella, J V Sorli, F Carmona, A Sanchez-Pla, J Salas-Salvadó, C Andres-Lacueva
AIM: To characterize the urinary metabolomic fingerprint and multi-metabolite signature associated with type 2 diabetes (T2D), and to classify the population into metabotypes related to T2D. METHODS: A metabolomics analysis using the1 H-NMR-based, non-targeted metabolomic approach was conducted to determine the urinary metabolomic fingerprint of T2D compared with non-T2D participants in the PREDIMED trial. The discriminant metabolite fingerprint was subjected to logistic regression analysis and ROC analyses to establish and to assess the multi-metabolite signature of T2D prevalence, respectively...
February 20, 2018: Diabetes & Metabolism
Jin Qu, Xin Zhao, Peter X Ma, Baolin Guo
Injectable hydrogels with multistimuli responsiveness to electrical field and pH as a drug delivery system have been rarely reported. Herein, we developed a series of injectable conductive hydrogels as "smart" drug carrier with the properties of electro-responsiveness, pH-sensitivity, and inherent antibacterial activity. The hydrogels were prepared by mixing chitosan-graft-polyaniline (CP) copolymer and oxidized dextran (OD) as a cross-linker. The chemical structures, morphologies, electrochemical property, swelling ratio, conductivity, rheological property, in vitro and in vivo biodegradation, and gelation time of hydrogels were characterized...
March 16, 2018: Acta Biomaterialia
Jason M Rohde, Kyle R Brimacombe, Li Liu, Michael E Pacold, Adam Yasgar, Dorian M Cheff, Tobie D Lee, Ganesha Rai, Bolormaa Baljinnyam, Zhuyin Li, Anton Simeonov, Matthew D Hall, Min Shen, David M Sabatini, Matthew B Boxer
Proliferating cells, including cancer cells, obtain serine both exogenously and via the metabolism of glucose. By catalyzing the first, rate-limiting step in the synthesis of serine from glucose, phosphoglycerate dehydrogenase (PHGDH) controls flux through the biosynthetic pathway for this important amino acid and represents a putative target in oncology. To discover inhibitors of PHGDH, a coupled biochemical assay was developed and optimized to enable high-throughput screening for inhibitors of human PHGDH...
February 27, 2018: Bioorganic & Medicinal Chemistry
Sagar B Kudchodkar, Hyeree Choi, Emma L Reuschel, Rianne Esquivel, Jackie Jin-Ah Kwon, Moonsup Jeong, Joel N Maslow, Charles C Reed, Scott White, J Joseph Kim, Gary P Kobinger, Pablo Tebas, David B Weiner, Kar Muthumani
Vaccines are considered one of the greatest advances in modern medicine. The global burden of numerous infectious diseases has been significantly reduced, and in some cases, effectively eradicated through the deployment of specific vaccines. However, efforts to develop effective vaccines against infectious pathogens such as influenza, HIV, dengue virus (DENV), chikungunya virus (CHIKV), Ebola virus, and Zika virus (ZIKV) have proven challenging. Zika virus is a mosquito-vectored flavivirus responsible for periodic outbreaks of disease in Africa, Southeast Asia, and the Pacific Islands dating back over 50 years...
March 16, 2018: Microbes and Infection
Xiaoni Liu, Shuang Wang, Jianji Xu, Buxin Kou, Dexi Chen, Yajie Wang, Xiaoxin Zhu
BACKGROUND: MicroRNAs(miRNAs)are involved in the initiation and progression of hepatocellular carcinoma. ESC, an extract of Stellerachamaejasme L, had been confirmed as a potential anti-tumor extract of Traditional Chinese Medicine. In light of the important role of miRNAs in hepatocellular carcinoma, we questioned whether the inhibitory effects of ESC on hepatocellular carcinoma (HCC) were associated with miRNAs. METHODS: The proliferation inhibition of ESC on HCC cells was measured with MTT assay...
March 20, 2018: BMC Complementary and Alternative Medicine
Julie A Lynch, Brygida Berse, Merry Rabb, Paul Mosquin, Rob Chew, Suzanne L West, Nicole Coomer, Daniel Becker, John Kautter
BACKGROUND: Tumor testing for mutations in the epidermal growth factor receptor (EGFR) gene is indicated for all newly diagnosed, metastatic lung cancer patients, who may be candidates for first-line treatment with an EGFR tyrosine kinase inhibitor. Few studies have analyzed population-level testing. METHODS: We identified clinical, demographic, and regional predictors of EGFR & KRAS testing among Medicare beneficiaries with a new diagnosis of lung cancer in 2011-2013 claims...
March 20, 2018: BMC Cancer
Zheng-Rong Lu, Peter Qiao
The treatment of malignancies has undergone dramatic changes in the past few decades. Advances in drug delivery techniques and nanotechnology have allowed for new formulations of old drugs, so as to improve the pharmacokinetics, to enhance accumulation in solid tumors, and to reduce the significant toxic effects of these important therapeutic agents. Here, we review the published clinical data in cancer therapy of several major drug delivery systems, including targeted radionuclide therapy, antibody drug conjugates, liposomes, polymer drug conjugates, polymer implants, micelles, and nanoparticles...
March 19, 2018: Molecular Pharmaceutics
Wei-Wei Tao, Jin-Gao Yu, Yan-Yan Chen, Dong Xiao, Jian-Ming Guo, Pei Liu, Jin-Ao Duan
The study was based on the toxic characteristics of the compatibility between "Zaojisuiyuan" and Gancao, with intestinal tract and intestinal bacteria as subject. From the angle of intestinal barrier function, motor function, steady state of intestinal flora and metabolism genes, the toxic and side effects of the compatibility between Qianjinzi and Gancao with similar properties, bases and chemical composition and types were further explored. The results showed that the combined application of Qianjinzi and Gancao enhanced intestinal mucosa damage, and led to abnormal changes in intestinal bacteria structure and metabolic function...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Sai-Sai Tian, Jian Yang, Jing Zhao, Wei-Dong Zhang
With the completion of the human genome project, people have gradually recognized that the functions of the biological system are fulfilled through network-type interaction between genes, proteins and small molecules, while complex diseases are caused by the imbalance of biological processes due to a number of gene expression disorders. These have contributed to the rise of the concept of the "multi-target" drug discovery. Treatment and diagnosis of traditional Chinese medicine are based on holism and syndrome differentiation...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Ya-Ping Xiao, Jie Zeng, Lin-Na Jiao, Xiao-Yu Xu
The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Andreas Domröse, Robin Weihmann, Stephan Thies, Karl-Erich Jaeger, Thomas Drepper, Anita Loeschcke
Microbial secondary metabolites represent a rich source of valuable compounds with a variety of applications in medicine or agriculture. Effective exploitation of this wealth of chemicals requires the functional expression of the respective biosynthetic genes in amenable heterologous hosts. We have previously established the TREX system which facilitates the transfer, integration and expression of biosynthetic gene clusters in various bacterial hosts. Here, we describe the yTREX system, a new tool adapted for one-step yeast recombinational cloning of gene clusters...
December 2017: Synthetic and Systems Biotechnology
Han-Qing Pang, Shi-Jun Yue, Yu-Ping Tang, Yan-Yan Chen, Ya-Jie Tan, Yu-Jie Cao, Xu-Qin Shi, Gui-Sheng Zhou, An Kang, Sheng-Liang Huang, Ya-Jun Shi, Jing Sun, Zhi-Shu Tang, Jin-Ao Duan
As a well-known traditional Chinese medicine (TCM) prescription, Xin-Sheng-Hua Granule (XSHG) has been applied in China for more than 30 years to treat postpartum diseases, especially anemia. However, underlying therapeutic mechanisms of XSHG for anemia were still unclear. In this study, plasma metabolomics profiling with UHPLC-QTOF/MS and multivariate data method was firstly analyzed to discover the potential regulation mechanisms of XSHG on anemia rats induced by bleeding from the orbit. Afterward, the compound-target-pathway network of XSHG was constructed by the use of network pharmacology, thus anemia-relevant signaling pathways were dissected...
2018: Frontiers in Pharmacology
Samaresh Sau, Katyayani Tatiparti, Hashem O Alsaab, Sushil K Kashaw, Arun K Iyer
Nanomedicines can be multifunctional drug delivery agents for cancer therapies. However, they have faced several challenges in clinical trials owing to poor targeting ability, insufficient tumor penetration, difficulty in synthesis and scale up, and limited understanding of interactions between a tumor and nanoparticles. In this regard, tumor muticomponent targeting drug delivery systems are a rational approach for developing tumor-site-specific therapeutics. One of the goals is to arrive at a ready-to-configure, combinatorial, reagent-free click-chemistry-based tumor multicomponent targeting nanoparticle library...
March 15, 2018: Drug Discovery Today
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