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Clinical and Translational Medicine

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https://www.readbyqxmd.com/read/29340951/a-perspective-on-multi-target-drug-discovery-and-design-for-complex-diseases
#1
Rona R Ramsay, Marija R Popovic-Nikolic, Katarina Nikolic, Elisa Uliassi, Maria Laura Bolognesi
Diseases of infection, of neurodegeneration (such as Alzheimer's and Parkinson's diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets...
January 17, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29335786/anti-inflammatory-and-antiplatelet-effects-of-non-vitamin-k-antagonist-oral-anticoagulants-in-acute-phase-of-ischemic-stroke-patients
#2
Taizen Nakase, Junta Moroi, Tatsuya Ishikawa
BACKGROUND: Recently, non-vitamin K antagonist oral anticoagulants such as direct thrombin and direct factor Xa inhibitors have been prescribed for prevention of embolic stroke. While in Japan, argatroban, also a direct thrombin inhibitor, is available for the treatment of atherothrombotic stroke patients. This study aimed to explore whether there is any differences between direct thrombin and direct factor Xa inhibitors regarding the inhibiting effect against thrombogenesis in the clinical setting of acute ischemic stroke...
January 12, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29318404/does-alk-rearrangement-predict-favorable-response-to-the-therapy-of-bevacizumab-plus-pemetrexed-in-advanced-non-small-cell-lung-cancer-case-report-and-literature-review
#3
Zhichao Liu, Youting Bao, Butuo Li, Xindong Sun, Linlin Wang
BACKGROUND: Advanced ALK-rearranged non-small cell lung cancer (NSCLC) patients will develop acquired resistance after anaplastic lymphoma kinase (ALK) inhibitors therapies. Vascular endothelial growth factor-A (VEGF-A) production and tumor vessel formation were found to be more significantly enriched in ALK-rearrangement NSCLC than that in epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene mutated NSCLC. However, the correlation between ALK rearrangement and the efficacy of bevacizumab (a recombinant humanized IgG1 monoclonal antibody targeting VEGF-A) was still elusive...
January 9, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29285690/using-single-cell-multiple-omics-approaches-to-resolve-tumor-heterogeneity
#4
REVIEW
Michael A Ortega, Olivier Poirion, Xun Zhu, Sijia Huang, Thomas K Wolfgruber, Robert Sebra, Lana X Garmire
It has become increasingly clear that both normal and cancer tissues are composed of heterogeneous populations. Genetic variation can be attributed to the downstream effects of inherited mutations, environmental factors, or inaccurately resolved errors in transcription and replication. When lesions occur in regions that confer a proliferative advantage, it can support clonal expansion, subclonal variation, and neoplastic progression. In this manner, the complex heterogeneous microenvironment of a tumour promotes the likelihood of angiogenesis and metastasis...
December 28, 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29238879/the-small-vesicular-culprits-the-investigation-of-extracellular-vesicles-as-new-targets-for-cancer-treatment
#5
REVIEW
Fumihiko Urabe, Nobuyoshi Kosaka, Yusuke Yoshioka, Shin Egawa, Takahiro Ochiya
Extracellular vesicles (EVs) are membranous vesicles released from almost all type of cells including cancer cells. EVs transfer their components, such as microRNAs (miRNAs), messenger RNAs, lipids and proteins, from one cell to another, affecting the target cells. Emerging evidence suggests that reciprocal interactions between cancer cells and the cells in their microenvironment via EVs drive disease progression and therapy resistance. Therefore, understanding the roles of EVs in cancer biology will provide us with new opportunities to treat patients...
December 13, 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29230567/cancer-nanomedicine-a-review-of-recent-success-in-drug-delivery
#6
REVIEW
Stephanie Tran, Peter-Joseph DeGiovanni, Brandon Piel, Prakash Rai
Cancer continues to be one of the most difficult global healthcare problems. Although there is a large library of drugs that can be used in cancer treatment, the problem is selectively killing all the cancer cells while reducing collateral toxicity to healthy cells. There are several biological barriers to effective drug delivery in cancer such as renal, hepatic, or immune clearance. Nanoparticles loaded with drugs can be designed to overcome these biological barriers to improve efficacy while reducing morbidity...
December 11, 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28782090/purified-umbilical-cord-derived-mesenchymal-stem-cell-treatment-in-a-case-of-systemic-lupus-erythematosus
#7
Christopher D Phillips, Pornpatcharin Wongsaisri, Thein Htut, Terry Grossman
INTRODUCTION: Systemic lupus erythematosus (SLE) is a multiple organ system autoimmune disorder for which there is no known cure. METHODS: We report a case of a young adult lady with SLE and Sjogren's with diagnostic and clinical resolution following purified umbilical cord derived mesenchymal stem cell (MSC) and globulin component protein macrophage activating factor (GcMAF) therapy in a combined multidisciplinary integrative medicine protocol. RESULTS: Our patient had complete reversal of all clinical and laboratory markers...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28782089/the-role-of-lipids-in-corneal-diseases-and-dystrophies-a-systematic-review
#8
REVIEW
Tyler G Rowsey, Dimitrios Karamichos
Corneal diseases are an extensive cause of blindness worldwide and continue to persist as a challenging public health concern. Recently, various lipid-based therapies have been advocated for the modulation of corneal diseases; however, the number of studies is still very limited. Here we focus on developments and challenges on lipid-based therapies for dry eye disease, diabetic neuropathy, and Fuchs' endothelial corneal dystrophy. All three diseases are highly prevalent conditions and involve corneal stress and inflammation...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28776171/the-role-of-heterogeneity-in-asthma-a-structure-to-function-perspective
#9
REVIEW
Justin K Lui, Kenneth R Lutchen
A number of methods have evolved through the years in probing the dysfunction that impacts mechanics and ventilation in asthma. What has been consistently found is the notion of heterogeneity that is not only captured in the frequency dependence of lung mechanics measurements but also rendered on imaging as patchy diffuse areas of ventilation defects. The degree of heterogeneity has been linked to airway hyperresponsiveness, a hallmark feature of asthma. How these heterogeneous constriction patterns lead to functional impairment in asthma have only been recently explored using computational airway tree models...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28770521/styrene-maleic-acid-encapsulated-raloxifene-micelles-for-management-of-inflammatory-bowel-disease
#10
Khaled Greish, Safa Taha, Anfal Jasim, Sara Abd Elghany, Ameera Sultan, Ali AlKhateeb, Manal Othman, Fang Jun, Sebastien Taurin, Moiz Bakhiet
BACKGROUND: Inflammatory bowel disease (IBD) comprises a group of disorders that manifest through chronic inflammation of the colon and small intestine. Although the exact cause of IBD is still unclear, dysfunctional immunoregulation involving overproduction of inflammatory cytokines such as TNF-α, and IL-6 have been implicated in pathogenesis. Current therapy relies on immunosuppression, cytotoxic drugs, and monoclonal antibodies against TNF-α. These classes of drugs have severe side-effects, especially when used for long duration...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28766182/lipidomics-and-anti-trypanosomatid-chemotherapy
#11
REVIEW
Michael Biagiotti, Sedelia Dominguez, Nader Yamout, Rachel Zufferey
BACKGROUND: Trypanosomatids such as Leishmania, Trypanosoma brucei and Trypanosoma cruzi belong to the order Kinetoplastida and are the source of many significant human and animal diseases. Current treatment is unsatisfactory and is compromised by the rising appearance of drug resistant parasites. Novel and more effective chemotherapeutics are urgently needed to treat and prevent these devastating diseases, which relies on the identification of essential, parasite specific targets that are absent in the host...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28755163/cxcl9-11-polymorphisms-are-associated-with-liver-fibrosis-in-patients-with-chronic-hepatitis-c-a-cross-sectional-study
#12
María Ángeles Jiménez-Sousa, Ana Zaida Gómez-Moreno, Daniel Pineda-Tenor, Luz Maria Medrano, Juan José Sánchez-Ruano, Amanda Fernández-Rodríguez, Tomas Artaza-Varasa, José Saura-Montalban, Sonia Vázquez-Morón, Pablo Ryan, Salvador Resino
BACKGROUND AND AIMS: CXCL9-11 polymorphisms are related to various infectious diseases, including hepatitis C virus (HCV) infection. In this study, we analyzed the association between CXCL9-11 polymorphisms and liver fibrosis in HCV-infected patients. METHODS: We performed a cross-sectional study in 389 patients who were genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using the Sequenom's MassARRAY platform. The primary outcome variable was the liver stiffness measurement (LSM)...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28752333/significance-of-long-chain-polyunsaturated-fatty-acids-in-human-health
#13
REVIEW
Rafael Zárate, Nabil El Jaber-Vazdekis, Noemi Tejera, José A Pérez, Covadonga Rodríguez
In the last decades, the development of new technologies applied to lipidomics has revitalized the analysis of lipid profile alterations and the understanding of the underlying molecular mechanisms of lipid metabolism, together with their involvement in the occurrence of human disease. Of particular interest is the study of omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFAs), notably EPA (eicosapentaenoic acid, 20:5n-3), DHA (docosahexaenoic acid, 22:6n-3), and ARA (arachidonic acid, 20:4n-6), and their transformation into bioactive lipid mediators...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28748360/autophagy-and-inflammation
#14
REVIEW
Mengjia Qian, Xiaocong Fang, Xiangdong Wang
Autophagy is a homeostatic mechanism involved in the disposal of damaged organelles, denatured proteins as well as invaded pathogens through a lysosomal degradation pathway. Recently, increasing evidences have demonstrated its role in both innate and adaptive immunity, and thereby influence the pathogenesis of inflammatory diseases. The detection of autophagy machinery facilitated the measurement of autophagy during physiological and pathophysiological processes. Autophagy plays critical roles in inflammation through influencing the development, homeostasis and survival of inflammatory cells, including macrophages, neutrophils and lymphocytes; effecting the transcription, processing and secretion of a number of cytokines, as well as being regulated by cytokines...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28744848/systems-and-precision-medicine-approaches-to-diabetes-heterogeneity-a-big-data-perspective
#15
Enrico Capobianco
Big Data, and in particular Electronic Health Records, provide the medical community with a great opportunity to analyze multiple pathological conditions at an unprecedented depth for many complex diseases, including diabetes. How can we infer on diabetes from large heterogeneous datasets? A possible solution is provided by invoking next-generation computational methods and data analytics tools within systems medicine approaches. By deciphering the multi-faceted complexity of biological systems, the potential of emerging diagnostic tools and therapeutic functions can be ultimately revealed...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28646367/ifn%C3%AE-producing-cd4-t-lymphocytes-the-double-edged-swords-in-tuberculosis
#16
Pawan Kumar
IFNγ-producing CD4(+) T cells (IFNγ(+)CD4(+) T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ(+)CD4(+) T cells in TB pathogenesis. High frequency of IFNγ(+)CD4(+) T cells is the most invariable feature of the active disease...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28639235/biofluid-lipidome-a-source-for-potential-diagnostic-biomarkers
#17
REVIEW
Arkasubhra Ghosh, Krishnatej Nishtala
Lipidomics is the identification and quantitation of changes in the lipidome of a cell, tissue, organ or biofluid in health and disease using high resolution mass spectrometry. Lipidome of a particular organism has relevance to the disease manifestation as it reflects the metabolic changes which can be a consequence of the disease. Hence these changes in the molecules can be considered as potential markers for screening and early detection of the disease. Biological fluids as blood/serum/plasma, urine, saliva, tear and cerebrospinal fluid, due to their accessibility, offer ease of collection with minimal or no discomfort to the patient and provide a ready footprint of the metabolic changes occurring during disease...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28597408/single-cell-rna-sequencing-of-the-brain
#18
REVIEW
Raquel Cuevas-Diaz Duran, Haichao Wei, Jia Qian Wu
Single-cell RNA-sequencing (scRNA-seq) is revolutionizing our understanding of the genomic, transcriptomic and epigenomic landscapes of cells within organs. The mammalian brain is composed of a complex network of millions to billions of diverse cells with either highly specialized functions or support functions. With scRNA-seq it is possible to comprehensively dissect the cellular heterogeneity of brain cells, and elucidate their specific functions and state. In this review, we describe the current experimental methods used for scRNA-seq...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28577109/phosgene-induced-acute-lung-injury-ali-differences-from-chlorine-induced-ali-and-attempts-to-translate-toxicology-to-clinical-medicine
#19
REVIEW
Wenli Li, Juergen Pauluhn
BACKGROUND: Phosgene (carbonyl dichloride) gas is an indispensable chemical inter-mediate used in numerous industrial processes. There is no clear consensus as to its time- and inhaled-dose-dependent etiopathologies and associated preventive or therapeutic treatment strategies. METHODS: Cardiopulmonary function was examined in rats exposed by inhalation to the alveolar irritant phosgene or to the airway irritant chlorine during and following exposure. Terminal measurements focused on hematology, protein extravasation in bronchoalveolar lavage (BAL), and increased lung weight...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28510121/can-glypican-3-be-a-disease-specific-biomarker
#20
REVIEW
Chaolei Chen, Xiaomin Huang, Zhaojian Ying, Dengmin Wu, Yani Yu, Xiangdong Wang, Chengshui Chen
BACKGROUND: Glypican-3 (GPC3) is a cell surface-bound proteoglycan which has been identified as a potential biomarker candidate in hepatocellular carcinoma, lung carcinoma, severe pneumonia, and acute respiratory distress syndrome (ARDS). The aim of our review is to evaluate whether GPC3 has utility as a disease-specific biomarker, to discuss the potential involvement of GPC3 in cell biology, and to consider the changes of GPC3 gene and protein expression and regulation in hepatocellular carcinoma, lung cancer, severe pneumonia, and ARDS...
December 2017: Clinical and Translational Medicine
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