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Cell mechanics

Michael Platten, David A Reardon
Strategies to empower the immune system to successfully attack cancers, including vaccination approaches, adaptive T cell therapies, and immune checkpoint modulators, have recently achieved remarkable success across a spectrum of cancer indications. Nonetheless, with rare exception, only a minority of patients with a given type of cancer respond to an immunotherapeutic when administered as single-agent therapy. Although under extensive laboratory and clinical investigation, the role of these approaches for glioma patients remains to be determined...
February 2018: Seminars in Neurology
Po-Han Chen, Jen-Tsan Chi, Michael Boyce
In metazoans, thousands of intracellular proteins are modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to a wide range of stimuli and stresses. In particular, a complex and evolutionarily conserved interplay between O-GlcNAcylation and oxidative stress has emerged in recent years. Here, we review the current literature on the connections between O-GlcNAc and oxidative stress, with a particular emphasis on major signaling pathways, such as KEAP1/NRF2, FOXO, NFκB, p53 and cell metabolism...
March 14, 2018: Glycobiology
Shiqi Luo, Feng He, Junjie Luo, Shengqian Dou, Yirong Wang, Annan Guo, Jian Lu
Transfer RNA-derived small RNAs (tsRNAs) are an emerging class of small RNAs, yet their regulatory roles have not been well understood. Here we studied the molecular mechanisms and consequences of tsRNA-mediated regulation in Drosophila. By analyzing 495 public small RNA libraries, we demonstrate that most tsRNAs are conserved, prevalent and abundant in Drosophila. By carrying out mRNA sequencing and ribosome profiling of S2 cells transfected with single-stranded tsRNA mimics and mocks, we show that tsRNAs recognize target mRNAs through conserved complementary sequence matching and suppress target genes by translational inhibition...
March 14, 2018: Nucleic Acids Research
Joel D Ernst, Amber Cornelius, Ludovic Desvignes, Jacqueline Tavs, Brian A Norris
Infection with M. tuberculosis is associated with inconsistent and incomplete elimination of the bacteria, despite development of antigen-specific T cell responses. One mechanism employed by M. tuberculosis is to limit availability of antigen for activation of CD4 T cells. We examined the utility of systemic administration of epitope peptides to activate pre-existing T cells in mice infected with M. tuberculosis. We found that systemic peptide administration: 1) selectively activates T cells specific for the epitope peptide; 2) loads MHC class II on lung macrophages and dendritic cells; 3) activates CD4 T cells in the lung parenchyma; 4) has little antimycobacterial activity...
March 14, 2018: Journal of Infectious Diseases
Min Young Kim, Ji Sook Kim, Seung Han Son, Chang Su Lim, Hea Young Eum, Dae Hyun Ha, Mi Ae Park, Eun Jung Baek, Buom-Yong Ryu, Ho Chul Kang, Vladimir N Uversky, Chul Geun Kim
During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes. We found that both Mbd2 and Mbd3 expression is downregulated during differentiation of MEL cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis...
March 14, 2018: Nucleic Acids Research
Jiang He, Yuzu Zhao, Erhu Zhao, Xianxing Wang, Zhen Dong, Yibiao Chen, Liqun Yang, Hongjuan Cui
Background: The cancer-testis specific gene Opa interacting protein 5 (OIP5) is a testis-specific gene that is reactivated in many human cancers, but its functions in glioblastoma remain unclear. Here, we assessed the significance of OIP5 in the tumorigenesis and metastasis of glioblastoma for the first time. Methods: An immunohistochemistry assay was performed to detect OIP5 expression changes in glioblastoma patients. Overall survival analysis was performed to evaluate the prognostic significance of OIP5...
March 14, 2018: Neuro-oncology
Konstadinos Plestis, Oleg Orlov, Vishal N Shah, Joshua Wong, Matthew Thomas, Alon Aharon, Cinthia Orlov, Georgia Panagopoulos, Scott Goldman
OBJECTIVES: Minimally invasive aortic valve replacement (MIAVR) can be technically demanding and may lead to prolonged operative time. We evaluated the intraoperative and postoperative patient outcomes following implementation of 2 facilitating technologies (FT) in MIAVR: the Cor-Knot titanium fastener and Custodiol-histidine-tryptophan-ketoglutarate solution. METHODS: A total of 299 patients underwent MIAVR from 2008 to 2016; 172 (57.5%) patients were included in the FT group and 127 (42...
March 14, 2018: Interactive Cardiovascular and Thoracic Surgery
Yilun Deng, Yuejuan Qin, Subramanya Srikantan, Anqi Luo, Zi-Ming Cheng, Shahida K Flores, Kris S Vogel, Exing Wang, Patricia L M Dahia
The TMEM127 tumor suppressor gene encodes a transmembrane protein of unknown function mutated in pheochromocytomas and, rarely, in renal cancers. Tumors with inactivating TMEM127 mutations have increased mTORC1 signaling by undefined mechanisms. Here we report that TMEM127 interacts with the lysosome-anchored complex comprised of Rag GTPases, the LAMTOR pentamer (or 'ragulator') and vATPase, which controls amino acid-mediated mTORC1 activation. We found that in nutrient-rich conditions TMEM127 expression reduces mTORC1 recruitment to Rags...
March 14, 2018: Human Molecular Genetics
Kelsey A Herrmann, Heather T Broihier
Although retrograde neurotrophin signaling has provided an immensely influential paradigm for understanding growth factor signaling in the nervous system, recent studies indicate that growth factors also signal via cell-autonomous, or autocrine, mechanisms. Autocrine signals have been discovered in many neuronal contexts, providing insights into their regulation and function. The growing realization of the importance of cell-autonomous signaling stems from advances in both conditional genetic approaches and in sophisticated analyses of growth factor dynamics, which combine to enable rigorous in vivo dissection of signaling pathways...
March 13, 2018: Current Opinion in Neurobiology
Xi Wu, Xue Xue, Lihui Wang, Wenjing Wang, Jian Han, Xiaoxue Sun, Haotian Zhang, Yueyang Liu, Xiaohang Che, Jingyu Yang, Chunfu Wu
Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis. Disulfiram (DSF), a drug widely used to control alcoholism, possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. Our previous studies proved that DSF/Cu exerts increased anti-tumor effects on non-small cell lung cancer (NSCLC) xenograft models, and inhibits NSCLC recurrence driven by ALDH-positive cancer stem cells...
March 13, 2018: European Journal of Pharmacology
Mousumi Pal, Utpal Nandi, Debaraj Mukherjee
Ruthenium (Ru) complexes are known for their promising anticancer activity presumably due to octahedral coordination geometry, slow ligand exchange rate, the range of different oxidation states and target specificity. This review article summarizes the physicochemical processes which are responsible for the selectivity of Ru complexes toward cancer cells over the normal cells. Emphasis has been given on the activation mechanism of Ru(III) complex administered as a prodrug and then the release of active species in an acidic environment of cancer cell through normal or photo induced hydrolysis or ligand oxidation...
March 7, 2018: European Journal of Medicinal Chemistry
Asmaa E Kassab, Ehab M Gedawy
As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC50 values against the most sensitive cancer cell lines...
March 9, 2018: European Journal of Medicinal Chemistry
Yi Yan, Vitor Sencadas, Tiantian Jin, Xufeng Huang, Wilford Lie, Dongbin Wei, Zhengyi Jiang
Processing conditions deeply affect the mechanical, chemical and biological properties of elastomeric based nanocomposites. In this work, multi-walled carbon nanotubes (MWCNTs) were dispersed in poly(glycerol sebacate) (PGS) prepolymer, followed by curing under vacuum at 120 °C. It was observed an increase of the water contact angle with the amount of MWCNTs added, as well as the tensile strength and Young modulus, without compromising the elastomeric behaviour of the pristine PGS matrix. The cross-linking degree was determined by the Flory-Rehner swelling method and through the mechanical rubber elasticity model, and an increase of more than six-fold was observed, which demonstrates the chemical conjugation between the MWCNTs and the PGS polymer chains, resulting in stiff and elastomeric nanocomposites...
March 7, 2018: Journal of Colloid and Interface Science
Jialiang Liang, Fuyang Liu, Mian Li, Wen Liu, Meiping Tong
Magnetic Fe3 O4 @BiOI@AgI (FBA) spheres were synthesized through a multi-step process. The fabricated photocatalysts were characterized by different techniques. To testify the visible light driven photocatalytic activity of FBA, Rhodamine B and Bisphenol A were chosen as model common and emerging organic contaminants, respectively. While, gram-negative strain Escherichia coli was selected as model waterborne bacteria. The results showed that under visible light irradiation, FBA contained strong photocatalytic degradation capacity towards both RhB and BPA...
March 10, 2018: Water Research
Ariana Sherdil, Stéphan Chabardès, Isabelle Guillemain, Sandrine Michallat, Shivadatta Prabhu, Karine Pernet-Gallay, Olivier David, Brigitte Piallat
PURPOSE: Our objective was to propose a new on demand non-human primate model of mesial temporal lobe seizures suitable for pre-clinical innovative therapeutic research. METHODS: Five macaques were stereotaxically implanted unilaterally with a deep recording electrode in the hippocampus. For each experiment, penicillin was injected into the hippocampus and animals were monitored during five consecutive hours. A total of 12-27 experiments with a mean cumulative dose of 162644 ± 70190 UI of penicillin have been performed per animal Injections were repeated at least once a week over a period of 98-276 days...
March 9, 2018: Epilepsy Research
Evgenii Tcyganov, Jerome Mastio, Eric Chen, Dmitry I Gabrilovich
In recent years, myeloid-derived suppressor cells (MDSC) have emerged as one of the major inhibitors of immune effector cell function in cancer. MDSC represent a heterogeneous population of largely immature myeloid cells that are characterized by a pathological state of activation and display potent immune suppressive activity. Two major subsets of MDSC have been identified: monocytic (M-MDSC) and polymorphonuclear (PMN-MDSC). PMN-MSDC share phenotypic and morphologic features with neutrophils, whereas M-MDSC are similar to monocytes and are characterized by high plasticity...
March 13, 2018: Current Opinion in Immunology
Tao Wei, Lei Liu, Xiaoying Zhou
Airway smooth muscle (ASM) is a prominent effecter in maintaining bronchial muscle contraction and responsible for airway hyper-responsiveness (AHR); the phenotype change and over-proliferation of airway smooth muscle cells (ASMCs) play key roles in the pathogenesis of asthma. The aim of this study was to investigate the anti-proliferation effects of Cortex Dictamni aqueous extract (CDAE) and ethanol extract (CDE) on ASMCs and the possible underline mechanisms. Cell proliferation rates were determined by MTT assay; matrix metalloproteinases-2 (MMP-2) activity was examined by gelatin zymography; cell proliferation and migration were appraised by in-vitro cell-gap closure assessment; protein expressions of p38, Bcl-2 and FAK of ASMCs were evaluated by western blotting and Ca2+ influx of cells was measured by confocal laser microscope...
March 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Kenneth D Swanson, Bin Zheng
In this issue of Molecular Cell, Lin et al. (2018) report that chondroitin-4-sulfate, which is found in a common supplement meant to alleviate degenerative joint disorders, promotes the growth of BRAF V600E mutant melanoma. This study not only has implications for patient care but also sheds light on a novel mechanism for regulating phosphoinositide 3-kinase signaling.
March 15, 2018: Molecular Cell
Joseph D Turner, Nicolas Pionnier, Julio Furlong-Silva, Hanna Sjoberg, Stephen Cross, Alice Halliday, Ana F Guimaraes, Darren A N Cook, Andrew Steven, Nico Van Rooijen, Judith E Allen, Stephen J Jenkins, Mark J Taylor
Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection...
March 16, 2018: PLoS Pathogens
Nasir Mehmood, Ranim Alayoubi, Eric Husson, Cédric Jacquard, Jochen Büchs, Catherine Sarazin, Isabelle Gosselin
Imidazolium ionic liquids (ILs) are promising solvents for lignocellulosic biomass (LCB) pretreatment and allow the achievement of higher ethanolic yields after enzymatic hydrolysis and ethanolic fermentation. However, residual ILs entrapped in pretreated biomass are often toxic for fermentative microorganisms, but interaction mechanisms between ILs and cells are still unknown. Here we studied the effects of 1-ethyl-3-methylimidazolium acetate [Emim][OAc] and 1-ethyl-3-methylimidazolium methylphosphonate [Emim][MeO(H)PO₂] on Kluyveromyces marxianus , a thermotolerant ethanologenic yeast...
March 16, 2018: International Journal of Molecular Sciences
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