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Disease resistance

Michelle J Wilkinson, Henry G Smith, Gráinne McEntee, Joan Kyula-Currie, Tim D Pencavel, David C Mansfield, Aadil A Khan, Victoria Roulstone, Andrew J Hayes, Kevin J Harrington
Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity...
October 22, 2016: Oncotarget
Tina Bernadette Angerer, Ylva Magnusson, Goran Landberg, John Stephen Fletcher
Breast cancer is an umbrella term used to describe a collection of different diseases with broad inter- and intra-tumor heterogeneity. Understanding this variation is critical in order to develop, and precisely prescribe, new treatments. Changes in the lipid metabolism of cancerous cells can provide important indications as to the metabolic state of the cells but are difficult to investigate with conventional histological methods. Due to the introduction of new higher energy (40 kV) gas cluster ion beams (GCIBs) time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is now capable of providing information on the distribution of hundreds of molecular species simultaneously on a cellular to sub-cellular scale...
October 26, 2016: Analytical Chemistry
Hiroshi Kaji
Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner...
September 15, 2016: Comprehensive Physiology
Laura Denise Mendes da Silva, Mariana Gatto, Mariana Miziara de Abreu Teodoro, Marjorie de Assis Golim, Érika Alessandra Pelisson Nunes da Costa, Francilene Capel Tavares Carvalho, Daniela Ramos Rodrigues, Paulo Câmara Marques Pereira, Ângela Maria Victoriano de Campos Soares, Sueli Aparecida Calvi
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi is a serious public health issue. Its evolution involves an acute stage, characterized by no specific symptoms, and the chronic stage during most individuals are asymptomatic, but about 30 to 40% of them become symptomatic presenting the cardiac or digestive disease. Host immune response mechanisms involved in symptomatic or asymptomatic chronic disease are not fully understood. The pro-inflammatory cytokines are crucial in host resistance. However, a fine control of this inflammatory process, by action of anti-inflammatory cytokines, is necessary to avoid tissue injury...
October 26, 2016: Scandinavian Journal of Immunology
Charles Dalcanale Tesser, Armando Henrique Norman
This article contends that the distinction between clinical care (illness) and prevention of future disease is essential to the practice of quaternary prevention. The authors argue that the ongoing entanglement of clinical care and prevention transforms healthy into "sick" people through changes in disease classification criteria and/or cut-off points for defining high-risk states. This diverts health care resources away from those in need of care and increases the risk of iatrogenic harm in healthy people...
October 20, 2016: Cadernos de Saúde Pública
Jonathan D Hibshman, Anthony Hung, L Ryan Baugh
Maternal effects of environmental conditions produce intergenerational phenotypic plasticity. Adaptive value of these effects depends on appropriate anticipation of environmental conditions in the next generation, and mismatch between conditions may contribute to disease. However, regulation of intergenerational plasticity is poorly understood. Dietary restriction (DR) delays aging but maternal effects have not been investigated. We demonstrate maternal effects of DR in the roundworm C. elegans. Worms cultured in DR produce fewer but larger progeny...
October 2016: PLoS Genetics
Dhiviya Prabaa Muthuirulandi Sethuvel, Naveen Kumar Devanga Ragupathi, Shalini Anandan, Balaji Veeraraghavan
Shigellosis represents a major burden of disease in developing countries. A low infectious dose allows the disease to be spread effectively. Although shigellosis is mostly a self-limiting disease, antibiotics are recommended to reduce deaths, disease symptoms, and organism-shedding time. However, In India, antimicrobial resistance among the genus Shigella is more common than among any other enteric bacteria. Notably, new serotypes or subserotypes in Shigella are reported from various parts of the world. Identification of new subserotypes of Shigella spp is becoming a major issue as these strains are non-typeable by conventional serotyping...
October 26, 2016: Letters in Applied Microbiology
F G A Silva, M F S F de Moura, N Dourado, J Xavier, F A M Pereira, J J L Morais, M I R Dias, P J Lourenço, F M Judas
Fracture characterization of human cortical bone under mode II loading was analyzed using a miniaturized version of the end-notched flexure test. A data reduction scheme based on crack equivalent concept was employed to overcome uncertainties on crack length monitoring during the test. The crack tip shear displacement was experimentally measured using digital image correlation technique to determine the cohesive law that mimics bone fracture behavior under mode II loading. The developed procedure was validated by finite element analysis using cohesive zone modeling considering a trapezoidal with bilinear softening relationship...
October 25, 2016: Medical & Biological Engineering & Computing
Paola Cipriani, Onorina Berardicurti, Francesco Masedu, Francesca D'Onofrio, Luca Navarini, Piero Ruscitti, Nicola Maruotti, Domenico Paolo Emanuele Margiotta, Vasiliki Liakouli, Paola Di Benedetto, Francesco Carubbi, Marco Valenti, Francesco Paolo Cantatore, Antonella Afeltra, Roberto Giacomelli
Since the introduction of biologics, many concerns about the increased risk of infections have been reported and, to date, the real impact of infections on the daily practice in the rheumatologic centers is still largely unknown. In this work, we evaluated the infection rates associated with the use of biologics in a large cohort of patients. A prospective study, between January 2010 and December 2013, enrolling 731 rheumatic patients, was performed. Demographic and disease characteristics, therapies, comorbidities, and infectious events were recorded and statistically analyzed by multivariate analysis...
October 25, 2016: Clinical Rheumatology
Takuya Hirai, Keigo Ikeda, Maki Fujishiro, Hiroshi Tsushima, Kunihiro Hayakawa, Satoshi Suzuki, Ayako Yamaguchi, Kazuhisa Nozawa, Shinji Morimoto, Yoshinari Takasaki, Hideoki Ogawa, Kenji Takamori, Naoto Tamura, Iwao Sekigawa
The study aims to confirm the feasibility of new oral triple combination therapy using methotrexate (MTX), mizoribine (MZR), and tacrolimus (TAC) in patients with rheumatoid arthritis (RA) by in vitro and clinical analyses. Triple therapy with a combination of MTX, MZR, and TAC was used for an in vitro study with osteoclasts and a prospective clinical study in order to show the efficacy of these agents against refractory RA. In particular, low-dose TAC or MZR was added to treat 14 patients with RA that was resistant to MTX + MZR or MTX + TAC dual therapy...
October 25, 2016: Clinical Rheumatology
Arielle Salmier, Benoit de Thoisy, Brigitte Crouau-Roy, Vincent Lacoste, Anne Lavergne
BACKGROUND: Although bats are natural reservoirs of many pathogens, few studies have been conducted on the genetic variation and detection of selection in major histocompatibility complex (MHC) genes. These genes are critical for resistance and susceptibility to diseases, and host-pathogen interactions are major determinants of their extensive polymorphism. Here we examined spatial patterns of diversity of the expressed MHC class II DRB gene of three sympatric Neotropical bats, Carollia perspicillata and Desmodus rotundus (Phyllostomidae), and Molossus molossus (Molossidae), all of which use the same environments (e...
October 26, 2016: BMC Evolutionary Biology
Kun-Chun Chiang, Ta-Sen Yeh, Ren-Chin Wu, Jong-Hwei S Pang, Chi-Tung Cheng, Shang-Yu Wang, Horng-Heng Juang, Chun-Nan Yeh
Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 (LCN2) in human cholangiocarcinoma as a potential therapeutic target and diagnostic marker. So far, the role of LCN2 in cancer is still controversial and studies regarding the role of LCN2 in CCA are limited. LCN2 knockdown inhibited CCA cell growth in vitro and in vivo through induction of cell cycle arrest at G0/G1 phases and decreased metastatic potential due to repression of epithelial-mesenchymal transition (EMT)...
October 26, 2016: Scientific Reports
Patrick M Shih, Khanh Vuu, Nasim Mansoori, Leïla Ayad, Katherine B Louie, Benjamin P Bowen, Trent R Northen, Dominique Loqué
The advent and growth of synthetic biology has demonstrated its potential as a promising avenue of research to address many societal needs. However, plant synthetic biology efforts have been hampered by a dearth of DNA part libraries, versatile transformation vectors and efficient assembly strategies. Here, we describe a versatile system (named jStack) utilizing yeast homologous recombination to efficiently assemble DNA into plant transformation vectors. We demonstrate how this method can facilitate pathway engineering of molecules of pharmaceutical interest, production of potential biofuels and shuffling of disease-resistance traits between crop species...
October 26, 2016: Nature Communications
Qian Zhang, Xiaofang Sun, Xinhua Xiao, Jia Zheng, Ming Li, Miao Yu, Fan Ping, Zhixin Wang, Cuijuan Qi, Tong Wang, Xiaojing Wang
An adverse intrauterine environment, induced by a chromium-restricted diet, is a potential cause of metabolic disease in adult life. Up to now, the relative mechanism has not been clear. C57BL female mice were time-mated and fed either a control diet (CD), or a chromium-restricted diet (CR) throughout pregnancy and the lactation period. After weaning, some offspring continued the diet diagram (CD-CD or CR-CR), while other offspring were transferred to another diet diagram (CD-CR or CR-CD). At 32 weeks of age, glucose metabolism parameters were measured, and the liver from CR-CD group and CD-CD group was analyzed using a gene array...
October 22, 2016: International Journal of Molecular Sciences
Ehsan Malek, Byung-Gyu Kim, James J Driscoll
While the clinical benefit of proteasome inhibitors (PIs) for multiple myeloma (MM) treatment remains unchallenged, dose-limiting toxicities and the inevitable emergence of drug resistance limit their long-term utility. Disease eradication is compromised by drug resistance that is either present de novo or therapy-induced, which accounts for the majority of tumor relapses and MM-related deaths. Non-coding RNAs (ncRNAs) are a broad class of RNA molecules, including long non-coding RNAs (lncRNAs), that do not encode proteins but play a major role in regulating the fundamental cellular processes that control cancer initiation, metastasis, and therapeutic resistance...
October 6, 2016: Genes
Xiao-Huang Xu, Ting Li, Chi Man Vivienne Fong, Xiuping Chen, Xiao-Jia Chen, Yi-Tao Wang, Ming-Qing Huang, Jin-Jian Lu
Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins) and steroid saponins (dioscin, polyphyllin, and timosaponin) isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions...
October 5, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Xiao-Jun Xu, Hong-Sheng Wang, Xiu-Li Ju, Pei-Fang Xiao, Yan Xiao, Hong-Man Xue, Hong-Yu Shi, Yi-Jin Gao, Guo-Cun Jia, Xue-Rong Li, Wei-Hong Zhao, Ning-Ling Wang, Yong-Min Tang
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous disease with major diagnostic and therapeutic difficulties. A large-scale multicenter study of pediatric HLH is still lacking in China. PROCEDURE: The Histiocytosis Study Group of the Chinese Pediatric Society conducted this retrospective study in 2014. A total of 323 patients diagnosed with HLH between 2011 and 2013 from 12 hospitals were registered. RESULTS: The median age at diagnosis was 2...
October 26, 2016: Pediatric Blood & Cancer
Mohammad Naderan, Ali Jahanrad
PURPOSE: This study aimed at evaluating the effect of pregnancy on topographic, tomographic and biomechanical parameters of patients with keratoconus (KC) in comparison with non-pregnant patients with KC. METHOD: In a cohort study, patients with KC, whose disease was stable for at least 2 years, were evaluated before pregnancy, at their third trimester of pregnancy (34th week of pregnancy) and 6 months after pregnancy. As the control group, an equivalent number of age- and severity-matched non-pregnant female patients with KC were evaluated at the corresponding times...
October 26, 2016: Acta Ophthalmologica
Thomas Nicholson, Catherine Admay, Aaron Shakow, Salmaan Keshavjee
The human rights arguments that underpinned the fight against HIV over the last three decades were poised, but ultimately failed, to provide a similar foundation for success against multidrug-resistant TB (MDR-TB) and other diseases of the poor. With more than 1.5 million deaths since 2000 attributed to strains of MDR-TB, and with half a million new, and mostly untreated, MDR-TB cases in the world each year, the stakes could not be higher. The World Health Organization (WHO), whose mandate is to champion the attainment by all peoples of the highest possible level of health, recommended unsound medical treatment for MDR-TB patients in resource-poor settings from 1993-2002...
June 2016: Health and Human Rights
Leslie London, Helen Cox, Fons Coomans
The right to enjoy the benefits of scientific progress (REBSP) is a little-known but potentially valuable right that can contribute to rights-based approaches to addressing multidrug-resistant TB (MDR-TB). We argue that better understanding of the REBSP may help to advance legal and civil society action for health rights. While the REBSP does not provide an individual entitlement to have a new drug developed for MDR-TB, it sets up entitlements to expect a state to establish a legislative and policy framework aimed at developing scientific capacity to address the most important health issues and at disseminating the outcomes of scientific research...
June 2016: Health and Human Rights
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