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https://www.readbyqxmd.com/read/28526769/tam-receptor-tyrosine-kinases-in-cancer-drug-resistance
#1
REVIEW
Mikaella Vouri, Sassan Hafizi
Receptor tyrosine kinases (RTK) are major regulators of key biological processes, including cell growth, survival, and differentiation, and were established early on as proto-oncogenes, with aberrant expression linked to tumor progression in many cancers. Therefore, RTKs have emerged as major targets for selective therapy with small-molecule inhibitors. However, despite improvements in survival rates, it is now apparent that the targeting of RTKs with selective inhibitors is only transiently effective, as the majority of patients eventually become resistant to therapy...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28526474/recent-updates-on-third-generation-egfr-inhibitors-and-emergence-of-fourth-generation-egfr-inhibitors-to-combat-c797s-resistance
#2
REVIEW
Harun Patel, Rahul Pawara, Azim Ansari, Sanjay Surana
EGFR T790M mutation leads to resistance to most of clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development, which includes osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. On the other hand recently EGFR C797S mutation was reported to be a leading mechanism of resistance to the third-generation inhibitors. The C797S mutation appears to be an ideal target for overcoming the acquired resistance to the third generation inhibitors...
May 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28526271/an-in-vitro-urinary-catheterization-model-that-approximates-clinical-conditions-for-evaluation-of-innovations-to-prevent-catheter-associated-urinary-tract-infections
#3
R Y R Chua, K Lim, S S J Leong, P A Tambyah, B Ho
BACKGROUND: Catheter associated urinary tract infections (CAUTI) account for about 25% of nosocomial infections globally and often result in increased morbidity and healthcare costs. An added concern is the presence of microbial biofilms which are major reservoirs of bacteria, especially antibiotic resistant bacteria, in catheters. Since the practice of the closed drainage system, innovations to combat CAUTI have not produced significant improvements in clinical outcomes. The lack of a robust laboratory platform to test new CAUTI preventive strategies may impede development of novel technologies...
May 16, 2017: Journal of Hospital Infection
https://www.readbyqxmd.com/read/28525860/a-comparison-of-individual-exposure-perception-and-acceptable-levels-of-pm2-5-with-air-pollution-policy-objectives-in-china
#4
Lei Huang, Chao Rao, Tsering Jan van der Kuijp, Jun Bi, Yang Liu
Atmospheric pollution has emerged as a major public health issue in China. Public perception and acceptable risk levels of air pollution can prompt individual behavioral changes and play a major role in the public's response to health risks. Therefore, to explore these responses and evaluate what constitutes publicly acceptable concentrations of fine particulate matter (PM2.5), questionnaire surveys were conducted in three representative cities of China: Beijing, Nanjing, and Guangzhou. Great differences in public risk perception were revealed...
May 16, 2017: Environmental Research
https://www.readbyqxmd.com/read/28525348/obesity-prevalence-and-contributing-factors-among-adolescents-in-secondary-schools-in-pemagatshel-district-bhutan
#5
Wang Norbu, Ugyen Wangdi, Desang Dorji, Dumrongkiet Arthan, Ngamphol Soonthornworasiri, Pannamas Maneekan, Pimpimon Thongthien, Nantaporn Viravathana, Pattaneeya Prangthip
Background The prevalence of obesity has increased globally, with childhood and adolescent obesity being more common in developed countries. There has been no study on teenage obesity in Bhutan. In this study, we aimed to assess the prevalence of obesity in Bhutan for the first time in order to provide a baseline for future researchers. Methods The investigation, which included 392 adolescents, aimed to identify the prevalence of overweight and obesity and its contributing factors. Anthropometric measurements, food recall and knowledge, attitude, behaviour and environment questionnaires were administered...
May 18, 2017: International Journal of Adolescent Medicine and Health
https://www.readbyqxmd.com/read/28524859/mesenchymal-stem-cells-sense-mitochondria-released-from-damaged-cells-as-danger-signals-to-activate-their-rescue-properties
#6
Meriem Mahrouf-Yorgov, Lionel Augeul, Claire Crola Da Silva, Maud Jourdan, Muriel Rigolet, Sylvie Manin, René Ferrera, Michel Ovize, Adeline Henry, Aurélie Guguin, Jean-Paul Meningaud, Jean-Luc Dubois-Randé, Roberto Motterlini, Roberta Foresti, Anne-Marie Rodriguez
Mesenchymal stem cells (MSCs) protect tissues against cell death induced by ischemia/reperfusion insults. This therapeutic effect seems to be controlled by physiological cues released by the local microenvironment following injury. Recent lines of evidence indicate that MSC can communicate with their microenvironment through bidirectional exchanges of mitochondria. In particular, in vitro and in vivo studies report that MSCs rescue injured cells through delivery of their own mitochondria. However, the role of mitochondria conveyed from somatic cells to MSC remains unknown...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28524810/gender-and-leadership-for-health-literacy-to-combat-the-epidemic-rise-of-non-communicable-diseases
#7
Rufaro Manhanzva, Praise Marara, Theodore Duxbury, Amy Claire Bobbins, Noel Pearse, Erik Hoel, Thandi Mzizi, Sunitha C Srinivas
Until recently, the Non Communicable Diseases (NCD) epidemic has been considered only a significant burden to men in high-income countries. However, latest figures indicate that half of all NCD-related deaths affect women, especially in Low- and Middle-Income Countries (LMICs), with global responses to the NCD epidemic overlooking the significance of women and girls in their approaches and programmes. This case study highlights the burden of disease challenging South Africa that disproportionately affects women in the country, and suggests that the country, along with other LMICs internationally, requires a shift in the gender-based leadership of health literacy and self-empowerment...
May 19, 2017: Health Care for Women International
https://www.readbyqxmd.com/read/28524159/hallmarks-of-response-to-immune-checkpoint-blockade
#8
Alexandria P Cogdill, Miles C Andrews, Jennifer A Wargo
Unprecedented advances have been made in the treatment of cancer through the use of immune checkpoint blockade, with approval of several checkpoint blockade regimens spanning multiple cancer types. However, responses to this form of therapy are not universal, and insights are clearly needed to identify optimal biomarkers of response and to combat mechanisms of therapeutic resistance. A working knowledge of the hallmarks of cancer yields insight into responses to immune checkpoint blockade, although the focus of this is rather tumour-centric and additional factors are pertinent, including host immunity and environmental influences...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28523736/hyper-activation-of-%C3%AE-catenin-signalling-induced-by-ikk%C3%AE%C2%B5-inhibition-thwarts-colorectal-cancer-cell-proliferation
#9
Jie Chen, Jun Zhao, Xuan Chen, Chengming Ding, Katie Lee, Zeming Jia, Yaoting Zhang, Yuzheng Zhou, Chaoying Wei, Jiantai He, Zanxian Xia, Jian Peng
OBJECTIVE: Aberrant activation of Wnt/β-catenin signalling contributes significantly to the development of human colorectal cancers and β-catenin is the key signalling molecule transducing canonical Wnt/β-catenin signalling. Therefore, β-catenin is a promising therapeutic target for cancer treatment. This study demonstrates that the oncogenic IKKε kinase phosphorylates β-catenin to restrain its hyper activation, therefore promoting colorectal cancer (CRC) cell proliferation. MATERIALS AND METHODS: IKKε and β-catenin expression levels in human colorectal cancer tissues and cell lines were analysed by immunohistochemical staining and Western blotting...
May 19, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28523592/islet-microencapsulation-strategies-and-clinical-status-in-diabetes
#10
REVIEW
Mustafa Omami, James J McGarrigle, Mick Reedy, Douglas Isa, Sofia Ghani, Enza Marchese, Matthew A Bochenek, Maha Longi, Yuan Xing, Ira Joshi, Yong Wang, José Oberholzer
PURPOSE OF REVIEW: Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from the destruction of insulin-producing pancreatic β cells in the islets of Langerhans. Islet cell transplantation has become a successful therapy for specific patients with T1DM with hypoglycemic unawareness. The reversal of T1DM by islet transplantation is now performed at many major medical facilities throughout the world. However, many challenges must still be overcome in order to achieve continuous, long-term successful transplant outcomes...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28523289/core-canonical-pathways-involved-in-developing-human-glioblastoma-multiforme-gbm
#11
Somiranjan Ghosh, Sisir Dutta, Gabriel Thorne, Ava Boston, Alexis Barfield, Narendra Banerjee, Rayshawn Walker, Hirendra Nath Banerjee
Glioblastoma multiforme (GBM) is the most common and aggressive type of the primary brain tumors with pathologic hallmarks of necrosis and vascular proliferation. The diagnosis of GBM is currently mostly based on histological examination of brain tumor tissues, after radiological characterization and surgical biopsy. The ability to characterize tumors comprehensively at the molecular level raises the possibility that diagnosis can be made based on molecular profiling with or without histological examination, rather than solely on histological phenotype...
February 2017: Int J Sci Res Sci Eng Technol
https://www.readbyqxmd.com/read/28522817/lactobacillus-johnsonii-ameliorates-intestinal-extra-intestinal-and-systemic-pro-inflammatory-immune-responses-following-murine-campylobacter-jejuni-infection
#12
Stefan Bereswill, Ira Ekmekciu, Ulrike Escher, Ulrike Fiebiger, Kerstin Stingl, Markus M Heimesaat
Campylobacter jejuni infections are progressively increasing worldwide. Probiotic treatment might open novel therapeutic or even prophylactic approaches to combat campylobacteriosis. In the present study secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally reassociated with a commensal murine Lactobacillus johnsonii strain either 14 days before (i.e. prophylactic regimen) or 7 days after (i.e. therapeutic regimen) peroral C. jejuni strain 81-176 infection. Following peroral reassociation both C...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522681/endothelial-nox1-oxidase-assembly-in-human-pulmonary-arterial-hypertension-driver-of-gremlin1-mediated-proliferation
#13
Imad Al Ghouleh, Sanghamitra Sahoo, Daniel N Meijles, Jefferson H Amaral, Daniel S de Jesus, John Sembrat, Mauricio Rojas, Dmitry A Goncharov, Elena A Goncharova, Patrick J Pagano
Background: Pulmonary arterial hypertension (PAH) is a rapidly degenerating and devastating disease of increased pulmonary vessel resistance leading to right heart failure. Palliative modalities remain limited despite recent endeavors to investigate the mechanisms underlying increased pulmonary vascular resistance, i.e. aberrant vascular remodeling and occlusion. However, little is known of the molecular mechanisms responsible for endothelial proliferation, a root cause of PAH-associated vascular remodeling...
May 18, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28522597/alcohol-aging-and-innate-immunity
#14
REVIEW
Lisbeth A Boule, Elizabeth J Kovacs
The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28522365/knowns-and-unknowns-of-membrane-lipid-synthesis-in-streptomycetes
#15
Mario Sandoval-Calderón, Ziqiang Guan, Christian Sohlenkamp
Bacteria belonging to the genus Streptomyces are among the most prolific producers of antibiotics. Research on cellular membrane biosynthesis and turnover is lagging behind in Streptomyces compared to related organisms like Mycobacterium tuberculosis. While natural products discovery in Streptomyces is evidently a priority in order to discover new antibiotics to combat the increase in antibiotic resistant pathogens, a better understanding of this cellular compartment should provide insights into the interplay between core and secondary metabolism...
May 15, 2017: Biochimie
https://www.readbyqxmd.com/read/28522293/direct-action-of-adiponectin-ameliorates-increased-androgen-synthesis-and-reduces-insulin-receptor-expression-in-the-polycystic-ovary
#16
Anusha Singh, Puran Bora, Amitabh Krishna
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder of reproductive age females, leading to infertility. Despite extensive research, the exact pathophysiology and treatment are lacking. The aim of the current study was to evaluate the direct role of adiponectin either alone or together with luteinizing hormone (LH) on sex hormone synthesis and changes in insulin receptor (IR) in the ovary of dehydroepiandrosterone (DHEA)-treated PCOS-mice. Immunohistochemical study showed decreased expression of adiponectin receptor (AdipoR1) in PCOS-ovary which correlated with increased synthesis of androgen and decreased expression of IR...
May 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28522271/medroxyprogesterone-acetate-drives-m2-macrophage-differentiation-toward-a-phenotype-of-decidual-macrophage
#17
Yung-Chieh Tsai, Joseph T Tseng, Chia-Yih Wang, Mei-Tsz Su, Jyun-Yuan Huang, Pao-Lin Kuo
M1 macrophage differentiation plays a crucial role in enhanced inflammation during pregnancy, which may lead to pregnancy complications. Therefore, modulation of macrophage differentiation toward the M2 phenotype is desirable to ensure a successful pregnancy. Medroxyprogesterone acetate (MPA) is a potent progestin with an anti-inflammatory property, but its effect on macrophage differentiation is unknown. This study aimed to examine whether MPA can induce an M2 macrophage differentiation by using the human monocytes cell line THP-1 or primary monocytes...
May 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28522157/antiviral-goes-viral-harnessing-crispr-cas9-to-combat-viruses-in-humans
#18
REVIEW
Jasper Adriaan Soppe, Robert Jan Lebbink
The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a sequence-dependent manner, resulting in DNA cleavage by the endonuclease upon target binding. A rewired CRISPR/Cas9 system can be used for targeted and precise genome editing in eukaryotic cells. CRISPR/Cas has also been harnessed to target human pathogenic viruses as a potential new antiviral strategy...
May 15, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28522039/injectable-and-topical-neurotoxins-in-dermatology-indications-adverse-events-and-controversies
#19
REVIEW
Cerrene N Giordano, Seth L Matarasso, David M Ozog
The use of neuromodulators for therapeutic and cosmetic indications has proven to be remarkably safe. While aesthetic and functional adverse events are uncommon, each anatomic region has its own set of risks of which the physician and patient must be aware before treatment. The therapeutic usages of botulinum toxins now include multiple specialties and multiple indications. New aesthetic indications have also developed, and there has been an increased utilization of combination therapies to combat the effects of global aging...
June 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28522011/vaccination-with-a-live-attenuated-acinetobacter-baumannii-deficient-in-thioredoxin-provides-protection-against-systemic-acinetobacter-infection
#20
Sarah Ainsworth, Patrick M Ketter, Jieh-Juen Yu, Rose C Grimm, Holly C May, Andrew P Cap, James P Chambers, M Neal Guentzel, Bernard P Arulanandam
Multi-drug resistant Acinetobacter baumannii (MDR-Ab), an opportunistic pathogen associated with nosocomial and combat related infections, has a high mortality due to its virulence and limited treatment options. Deletion of the thioredoxin gene (TrxA) from a clinical isolate of MDR-Ab resulted in a 100-fold increase in 50% lethal dose (LD50) in a systemic challenge murine model. Thus, we investigated the potential use of this attenuated strain as a live vaccine against MDR-Ab. Mice were vaccinated by subcutaneous (s...
May 15, 2017: Vaccine
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