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https://www.readbyqxmd.com/read/29057791/emerging-therapeutics-to-overcome-chemoresistance-in-epithelial-ovarian-cancer-a-mini-review
#1
REVIEW
Robert Cornelison, Danielle C Llaneza, Charles N Landen
Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecologic malignancy. One of the leading causes of death in high-grade serous ovarian cancer (HGSOC) is chemoresistant disease, which may present as intrinsic or acquired resistance to therapies. Here we discuss some of the known molecular mechanisms of chemoresistance that have been exhaustively investigated in chemoresistant ovarian cancer, including drug efflux pump multidrug resistance protein 1 (MDR1), the epithelial-mesenchymal transition, DNA damage and repair capacity...
October 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29055013/a-synthetic-cd8%C3%AE-myd88-co-receptor-enhances-cd8-t-cell-responses-to-weakly-immunogenic-and-lowly-expressed-tumor-antigens
#2
Sabina Kaczanowska, Ann Mary Joseph, Jitao Guo, Alexander K Tsai, Jackline Joy M Lasola, Kenisha Younger, Yuji Zhang, Cruz Velasco Gonzalez, Eduardo Davila
T cell-based immunotherapies are a promising approach for patients with advanced cancers. However, various obstacles limit T cell efficacy, including suboptimal T cell receptor (TCR) activation and an immunosuppressive tumor environment. Here we developed a fusion protein by linking CD8α and MyD88 (CD8α:MyD88) to enhance CD8+ T cell responses to weakly immunogenic and poorly expressed tumor antigens. CD8α:MyD88-engineered T cells exhibited increased proliferation and expression of effector and co-stimulatory molecules in a tumor antigen-dependent manner...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29054519/nature-derived-scaffolds-for-tissue-engineering-applications-design-and-fabrication-of-a-composite-scaffold-incorporating-chitosan-g-d-l-lactic-acid-and-cellulose-nanocrystals-from-lactuca-sativa-l-cv-green-leaf
#3
Sung Won Ko, Juan Paolo E Soriano, Ji Yeon Lee, Afeesh Rajan Unnithan, Chan Hee Park, Cheol Sang Kim
Through exhaustive extraction via successive alkali and bleaching treatments cellulose was isolated from lettuce. The isolated cellulose was hydrolyzed using 64wt% H2SO4 at 55°C under constant stirring for 1h to obtain cellulose nanocrystals (CNCs). Characterizations such as SEM, TEM, FTIR, TGA and XRD were done in order to determine differences in the physico-chemical characteristics of cellulose after each treatment step. The isolated CNCs have mean dimensions of 237±26, 33±12 and 32±7nm in length, thickness and height, respectively...
October 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29053133/-ophthalmic-disorders-as-a-manifestation-of-parkinson-s-disease
#4
N B Chesnokova, T A Pavlenko, M V Ugrumov
Parkinson's disease is a severe neurodegenerative disease accompanied with the degeneration of dopaminergic neurons in the central and peripheral nervous system. The diagnosis of Parkinson's disease can still be made only on the stage of irreversible and nearly total degeneration of the nigrostriatum dopaminergic system and exhaustion of brain compensatory mechanisms that explains the low efficacy of therapy. Ophthalmic pathology is one of the nonmotor symptoms of Parkinson's disease. This can be explained firstly by the fact that eye is a 'peripheral part of brain' and secondly by the involvement of dopaminergic neurons (dopamine-producing cells) that are subject to the selective degeneration during Parkinson's disease in the regulation of visual function in the eye and brain...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29052507/metabolic-shift-in-density-dependent-stem-cell-differentiation
#5
Simar J Singh, William Turner, Drew E Glaser, Kara E McCloskey, Fabian V Filipp
BACKGROUND: Vascular progenitor cells (VPCs) derived from embryonic stem cells (ESCs) are a valuable source for cell- and tissue-based therapeutic strategies. During the optimization of endothelial cell (EC) inductions from mouse ESCs using our staged and chemically-defined induction methods, we found that cell seeding density but not VEGF treatment between 10 ng/mL and 40 ng/mL was a significant variable directing ESCs into FLK1(+) VPCs during stage 1 induction. Here, we examine potential contributions from cell-to-cell signaling or cellular metabolism in the production of VPCs from ESCs seeded at different cell densities...
October 20, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29051586/phosphatidylserine-induced-conformational-modulation-of-immune-cell-exhaustion-associated-receptor-tim3
#6
Jeffrey K Weber, Ruhong Zhou
In the face of chronic cancers and protracted viral infections, human immune cells are known to adopt an exhausted state in which their effector functions are lost. In recent years, a number of inhibitory receptors have been connected to the immune cell exhaustion phenotype; furthermore, ligands capable of activating these receptors have been discovered. The molecular mechanisms by which these ligands affect the exhausted states of immune cells, however, are largely unknown. Here, we present the results of molecular dynamics simulations of one potential exhaustion-associated system: the complex of human inhibitory receptor TIM3 (hTIM3) and its ligand phosphatidylserine (PSF)...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051561/magt1-mediated-disturbance-of-mg-2-homeostasis-lead-to-exhausted-of-hbv-infected-nk-and-cd8-t-cells
#7
Bo Diao, Xiaoyong Huang, Shen Guo, Chengying Yang, Guosong Liu, Yongwen Chen, Yuzhang Wu
The magnesium transporter 1 (MAGT1) is a critical regulator of basal intracellular free magnesium ([Mg(2+)]i) levels. It has been shown that MAGT1 was involved in the disorder in Mg(2+) homeostasis after Epstein-Barr virus (EBV) infection. Here, we identified the effects of MAGT1-mediated disturbance of Mg(2+) homeostasis on chronic hepatitis B virus (HBV)-infected natural killer (NK) and CD8(+) T cells. The expression of MAGT1 was gradually decreased with the increase of infected time in CD8(+) T cells, but not with that in NK cells, of the patients...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29050206/wnt-%C3%AE-catenin-signaling-promotes-aging-associated-hair-graying-in-mice
#8
Zhihui Zhang, Mingxing Lei, Haoran Xin, Chunyan Hu, Tian Yang, Yizhan Xing, Yuhong Li, Haiying Guo, Xiaohua Lian, Fang Deng
Canities is an obvious sign of aging in mouse and human, shown as hair graying. Melanocytes in the hair follicle show cyclic activity with hair cycling, which transitions from anagen, catagen to telogen. How the hairs turn gray during aging is not completely uncovered. Here, by using immunostaining and LacZ staining in Dct-LacZ mice, we show that β-catenin is expressed in melanocytes during hair cycling. RT-PCR, western blot and immunostaining show that β-catenin expression is significantly increased in both anagen and telogen skin of aged mice, when compared to the anagen and telogen skin of young mice, respectively...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29045899/early-transcriptional-divergence-marks-virus-specific-primary-human-cd8-t-cells-in-chronic-versus-acute-infection
#9
David Wolski, Peter K Foote, Diana Y Chen, Lia L Lewis-Ximenez, Catherine Fauvelle, Jasneet Aneja, Andreas Walker, Pierre Tonnerre, Almudena Torres-Cornejo, Daniel Kvistad, Sabrina Imam, Michael T Waring, Damien C Tully, Todd M Allen, Raymond T Chung, Jörg Timm, W Nicholas Haining, Arthur Y Kim, Thomas F Baumert, Georg M Lauer
Distinct molecular pathways govern the differentiation of CD8(+) effector T cells into memory or exhausted T cells during acute and chronic viral infection, but these are not well studied in humans. Here, we employed an integrative systems immunology approach to identify transcriptional commonalities and differences between virus-specific CD8(+) T cells from patients with persistent and spontaneously resolving hepatitis C virus (HCV) infection during the acute phase. We observed dysregulation of metabolic processes during early persistent infection that was linked to changes in expression of genes related to nucleosomal regulation of transcription, T cell differentiation, and the inflammatory response and correlated with subject age, sex, and the presence of HCV-specific CD4(+) T cell populations...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29044000/observation-on-shenqi-fuzheng-injection-combined-with-cefoxitin-sodium-after-cesarean-section
#10
Jingge Chen, Yumin Cheng, Xinxiang Ma, Yuanyuan Cao
This paper aims to observe the effect of Shenqi Fuzheng Injection combined with cefoxitin sodium after cesarean section. Clinical data of 126 puerperae were retrospectively analyzed. They randomized into control group and treatment group, and there were 63 cases in each group. Patients in control group were given Cefoxitin Sodium treatment. And patients in treatment group were given Shenqi Fuzheng Injection on the basis of control group. After 7 days of treatment, the clinical curative effect of the two groups was observed and compared...
July 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29043077/recent-advances-in-understanding-werner-syndrome
#11
REVIEW
Raghavendra A Shamanna, Deborah L Croteau, Jong-Hyuk Lee, Vilhelm A Bohr
Aging, the universal phenomenon, affects human health and is the primary risk factor for major disease pathologies. Progeroid diseases, which mimic aging at an accelerated rate, have provided cues in understanding the hallmarks of aging. Mutations in DNA repair genes as well as in telomerase subunits are known to cause progeroid syndromes. Werner syndrome (WS), which is characterized by accelerated aging, is an autosomal-recessive genetic disorder. Hallmarks that define the aging process include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication...
2017: F1000Research
https://www.readbyqxmd.com/read/29041864/targets-of-therapy-in-progressive-ms
#12
Hans Lassmann
Highly effective anti-inflammatory therapies have so far been developed for patients with relapsing/remitting multiple sclerosis, which also show some benefits in the early progressive stage of the disease. However, treatment options for patients, who have entered the progressive phase, are still limited. Disease starts as an inflammatory process, which induces focal demyelinating lesions in the gray and white matter. This stage of the disease dominates in the relapsing phase, extends into the early stages of progressive disease, and can be targeted by current anti-inflammatory treatments...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29040163/adipose-tissue-is-enriched-for-activated-and-late-differentiated-cd8-t-cells-and-shows-distinct-cd8-receptor-usage-compared-to-blood-in-hiv-infected-persons
#13
John R Koethe, Wyatt McDonnell, Arion Kennedy, Chike O Abana, Mark Pilkinton, Ian Setliff, Ivelin Georgiev, Louise Barnett, Cindy C Hager, Rita Smith, Spyros A Kalams, Alyssa Hasty, Simon Mallal
BACKGROUND: Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially pro-inflammatory T cell populations in adipose tissue among persons on long-term antiretroviral therapy, and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population. METHODS: We recruited 10 HIV-infected, overweight and obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression...
October 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29039848/high-throughput-dft-calculations-of-formation-energy-stability-and-oxygen-vacancy-formation-energy-of-abo3-perovskites
#14
Antoine A Emery, Chris Wolverton
ABO3 perovskites are oxide materials that are used for a variety of applications such as solid oxide fuel cells, piezo-, ferro-electricity and water splitting. Due to their remarkable stability with respect to cation substitution, new compounds for such applications potentially await discovery. In this work, we present an exhaustive dataset of formation energies of 5,329 cubic and distorted perovskites that were calculated using first-principles density functional theory. In addition to formation energies, several additional properties such as oxidation states, band gap, oxygen vacancy formation energy, and thermodynamic stability with respect to all phases in the Open Quantum Materials Database are also made publicly available...
October 17, 2017: Scientific Data
https://www.readbyqxmd.com/read/29038751/combining-graph-and-flux-based-structures-to-decipher-phenotypic-essential-metabolites-within-metabolic-networks
#15
Julie Laniau, Clémence Frioux, Jacques Nicolas, Caroline Baroukh, Maria-Paz Cortes, Jeanne Got, Camille Trottier, Damien Eveillard, Anne Siegel
BACKGROUND: The emergence of functions in biological systems is a long-standing issue that can now be addressed at the cell level with the emergence of high throughput technologies for genome sequencing and phenotyping. The reconstruction of complete metabolic networks for various organisms is a key outcome of the analysis of these data, giving access to a global view of cell functioning. The analysis of metabolic networks may be carried out by simply considering the architecture of the reaction network or by taking into account the stoichiometry of reactions...
2017: PeerJ
https://www.readbyqxmd.com/read/29035687/acute-glutamine-ingestion-modulates-lymphocytic-responses-to-exhaustive-exercise-in-the-heat
#16
Chen Zheng, Xiang-Ke Chen, Yue Zhou
The purpose of this study was to determine if acute intake of glutamine modulates homeostatic, hematologic, immune, and inflammatory responses to exhaustive exercise in the heat. Thirteen healthy untrained young men participated in this randomized, double-blind, placebo-controlled, crossover study. They served as their own control and completed two trials of treadmill exercise at 40% VO2max to exhaustion in a hot environment (38.0 ± 1.0 °C, 60.0 ± 5.0 % relative humidity, and 20.8% oxygen) following placebo (PLA) and glutamine (GLN) consumption...
October 16, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29033936/coinhibitory-receptor-expression-and-immune-checkpoint-blockade-maintaining-a-balance-in-cd8-t-cell-responses-to-chronic-viral-infections-and-cancer
#17
REVIEW
Isobel S Okoye, Michael Houghton, Lorne Tyrrell, Khaled Barakat, Shokrollah Elahi
In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called "immune checkpoints" by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29032765/recent-patent-advances-for-neurodegenerative-disorders-and-its-treatment
#18
Bhavna Kumar, Deepika Sharma
BACKGROUND: Neurodegenerative disorders are one of the common diseases that affect our society with tremendous medical and financial burdens. As a whole, neurodegeneration affects individuals of all ages, but becomes increasingly frequent with age, coming to affect a very large share of our elderly population which is severely affecting the patient, caregivers, and enormously increasing the financial burden of the nation. These diseases share a very complex nature, which often result from combined genetic, environment and pathogenic factors...
October 10, 2017: Recent Patents on Drug Delivery & Formulation
https://www.readbyqxmd.com/read/29032101/mitochondrial-activity-in-t-cells
#19
REVIEW
Gabriela Desdín-Micó, Gonzalo Soto-Heredero, María Mittelbrunn
Mitochondria fulfill important and diverse roles during the different stages of T cell adaptive responses. Here we discuss the role of the mitochondria in T cells from the initial steps of activation at the immune synapse to their participation in memory responses and T cell exhaustion. Mitochondria are relocated to the immune synapse in order to supply local ATP and to aid calcium signaling. During expansion and proliferation, mitochondrial reactive oxygen species drive proliferation. Aerobic glycolysis, glutaminolysis and fatty acid oxidation regulate the program of differentiation into effector or regulatory T cell subsets, and mitochondrial remodeling proteins are required for the long-lasting phenotype of memory cells...
October 12, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29031786/differentiation-and-protective-capacity-of-virus-specific-cd8-t-cells-suggest-murine-norovirus-persistence-in-an-immune-privileged-enteric-niche
#20
Vesselin T Tomov, Olesya Palko, Chi Wai Lau, Ajinkya Pattekar, Yuhang Sun, Ralitza Tacheva, Bertram Bengsch, Sasikanth Manne, Gabriela L Cosma, Laurence C Eisenlohr, Timothy J Nice, Herbert W Virgin, E John Wherry
Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8(+) T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8(+) T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion...
October 17, 2017: Immunity
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