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https://www.readbyqxmd.com/read/28934595/copd-alters-immune-cell-composition-and-immune-checkpoint-inhibitor-efficacy-in-nsclc
#1
Nicholas M Mark, Julia Kargl, Stephanie E Busch, Grace H Y Yang, Heather E Metz, Huajia Zhang, Jesse J Hubbard, Sudhakar N J Pipavath, David K Madtes, A McGarry Houghton
RATIONALE: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality; the pathogenesis of both involves aberrant immune functioning. OBJECTIVE: To profile the immune cell composition and function in patients with NSCLC and describe the effect of COPD on lung and tumor microenvironments. METHODS: We profiled resected lung and tumor tissue using flow cytometry and T-cell receptor sequencing in patients with and without COPD from a prospective cohort of patients undergoing resection of NSCLC...
September 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28934428/hiv-infected-children-have-elevated-levels-of-pd-1-memory-cd4-t-cells-with-low-proliferative-capacity-and-high-inflammatory-cytokine-effector-functions
#2
Julia Foldi, Lina Kozhaya, Bret McCarty, Mussa Mwamzuka, Fatma Marshed, Tiina Ilmet, Max Kilberg, Adam Kravietz, Aabid Ahmed, William Borkowsky, Derya Unutmaz, Alka Khaitan
Background: During human immunodeficiency virus (HIV) disease, chronic immune activation leads to T-cell exhaustion. PD-1 identifies "exhausted" CD8 T cells with impaired HIV-specific effector functions, but its role on CD4 T cells and in HIV-infected children is poorly understood. Methods: In a Kenyan cohort of vertically HIV-infected children, we measured PD-1+ CD4 T-cell frequencies and phenotype by flow cytometry and their correlation with HIV disease progression and immune activation...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934392/nceh-1-modulates-cholesterol-metabolism-and-protects-against-%C3%AE-synuclein-toxicity-in-a-c-elegans-model-of-parkinson-s-disease
#3
Siyuan Zhang, Samantha A Glukhova, Kim A Caldwell, Guy A Caldwell
Parkinson's disease (PD) is an aging-associated neurodegenerative disease affecting millions worldwide. Misfolding, oligomerization and accumulation of the human α-synuclein protein is a key pathological hallmark of PD and is associated with the progressive loss of dopaminergic neurons over the course of aging. Lifespan extension via the suppression of IGF-1/insulin-like signaling (IIS) offers a possibility to retard disease onset through induction of metabolic changes that provide neuroprotection. The nceh-1 gene of Caenorhabditis elegans encodes an ortholog of neutral cholesterol ester hydrolase 1 (NCEH-1), an IIS downstream protein that was identified in a screen as a modulator of α-synuclein accumulation in vivo...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934248/vps35-deficiency-impairs-slc4a11-trafficking-and-promotes-corneal-dystrophy
#4
Wei Liu, Fu-Lei Tang, Sen Lin, Kai Zhao, Lin Mei, Jian Ye, Wen-Cheng Xiong
Vps35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD). However, Vps35/retromer's function in the eye or the contribution of Vps35-deficiency to eye degenerative disorders remains to be explored. Here we provide evidence for a critical role of Vps35 in mouse corneal dystrophy. Vps35 is expressed in mouse and human cornea...
2017: PloS One
https://www.readbyqxmd.com/read/28934104/microwave-deposition-of-palladium-catalysts-on-graphite-spheres-and-reduced-graphene-oxide-sheets-for-electrochemical-glucose-sensing
#5
Jian-De Xie, Siyong Gu, Houan Zhang
This work outlines a synthetic strategy inducing the microwave-assisted synthesis of palladium (Pd) nanocrystals on a graphite sphere (GS) and reduced graphene oxide (rGO) supports, forming the Pd catalysts for non-enzymatic glucose oxidation reaction (GOR). The pulse microwave approach takes a short period (i.e., 10 min) to fast synthesize Pd nanocrystals onto a carbon support at 150 °C. The selection of carbon support plays a crucial role in affecting Pd particle size and dispersion uniformity. The robust design of Pd-rGO catalyst electrode displays an enhanced electrocatalytic activity and sensitivity toward GOR...
September 21, 2017: Sensors
https://www.readbyqxmd.com/read/28933824/pd-cu-oxide-nanoconjugate-at-zeolite-y-crystallite-crafting-the-mesoporous-channels-for-selective-oxidation-of-benzyl-alcohols
#6
Mukesh Sharma, Biraj Das, Mitu Sharma, Biplab K Deka, Young-Bin Park, Suresh K Bhargava, Kusum K Bania
Solid-state grinding of palladium and copper salts allowed the growth of palladium/copper oxide interface at the zeolite-Y surface. The hybrid nanostructured material was used as reusable heterogeneous catalyst for selective oxidation of various benzyl alcohols. The large surface area provided by the zeolite-Y matrix highly influenced the catalytic activity as well as the recyclability of the synthesized catalyst. Impregnation of PdO-CuO nanoparticles on zeolite crystallite leads to the generation of mesoporous channel that probably prevented the leaching of the metal-oxide nanoparticles and endorsed high mass transfer...
September 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28933786/pink1-interacts-with-%C3%AE-synuclein-and-abrogates-%C3%AE-synuclein-induced-neurotoxicity-by-activating-autophagy
#7
Jia Liu, Xue Wang, Yongquan Lu, Chunli Duan, Ge Gao, Lingling Lu, Hui Yang
Parkinson's disease (PD) is one of the most common neurodegenerative diseases, characterized by degeneration of dopaminergic neurons in the substantia nigra. α-synuclein (α-syn) and PTEN-induced putative kinase (PINK)1 are two critical proteins associated with the pathogenesis of PD. α-syn induces mitochondrial deficits and apoptosis, PINK1 was found to alleviate α-syn-induced toxicity, but the mechanistic details remain obscure. Here, we show that PINK1 interacts with α-syn mainly in the cytoplasm, where it initiates autophagy...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28933707/high-accuracy-automatic-classification-of-parkinsonian-tremor-severity-using-machine-learning-method
#8
Hyoseon Jeon, Woongwoo Lee, Hyeyoung Park, Hong Ji Lee, Sang Kyong Kim, Han Byul Kim, Beomseok Jeon, Kwang Suk Park
Although clinical aspirations for new technology to accurately measure and diagnose Parkinsonian tremors exist, automatic scoring of tremor severity using machine learning approaches has not yet been employed. Objective: This study aims to maximize the scientific validity of automatic tremor-severity classification using machine learning algorithms to score Parkinsonian tremor severity in the same manner as the Unified Parkinson's Disease Rating Scale (UPDRS) used to rate scores in real clinical practice...
September 21, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28933618/novel-cns-drug-discovery-and-development-approach-model-based-integration-to-predict-neuro-pharmacokinetics-and-pharmacodynamics
#9
Elizabeth C M de Lange, Willem van den Brink, Yumi Yamamoto, Wilhelmus E A de Witte, Yin Cheong Wong
CNS drug development has been hampered by inadequate consideration of CNS pharmacokinetic (PK), pharmacodynamics (PD) and disease complexity (reductionist approach). Improvement is required via integrative model-based approaches. Areas covered: The authors summarize factors that have played a role in the high attrition rate of CNS compounds. Recent advances in CNS research and drug discovery are presented, especially with regard to assessment of relevant neuro-PK parameters. Suggestions for further improvements are also discussed...
September 21, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28933540/metal-complexes-with-a-hexadentate-macrocyclic-diamine-tetracarbene-ligand
#10
Taotao Lu, Chu-Fan Yang, Li-Yi Zhang, Fan Fei, Xue-Tai Chen, Zi-Ling Xue
A hexadentate macrocyclic N-heterocyclic carbene (NHC) ligand precursor (H4L)(PF6)4 containing four benzimidazolium and two secondary amine groups, has been synthesized and characterized. Coordination chemistry of this new macrocyclic diamine-tetracarbene ligand has been studied by the synthesis of its Ag(I), Au(I), Ni(II), and Pd(II) complexes. Reactions of (H4L)(PF6)4 with different equiv of Ag2O result in Ag(I) complexes [Ag(H2L)](PF6)3 (1) and [Ag2(H2L)](PF6)4 (2). A mononuclear Au(I) complex [Au(H2L)](PF6)3 (3) and a trinuclear Au(I) complex [Au3(H2L)(Cl)2](PF6) (4) are obtained by transmetalation of 1 and 2 with AuCl(SMe2), respectively...
September 21, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28933155/catalyst-dependent-selective-hydrogenation-of-nitriles-selective-synthesis-of-tertiary-and-secondary-amines
#11
Yasunari Monguchi, Masahiro Mizuno, Tomohiro Ichikawa, Yuki Fujita, Eri Murakami, Tomohiro Hattori, Tomohiro Maegawa, Yoshinari Sawama, Hironao Sajiki
In the presence of palladium on carbon (Pd/C) as a catalyst, hydrogenation of aliphatic nitriles in cyclohexane efficiently proceeded at 25-60 °C under ordinary hydrogen gas pressure to afford the corresponding tertiary amines. On the other hand, the use of rhodium on carbon (Rh/C) led to the highly selective generation of secondary amines. Hy-drogenation of aromatic nitriles and cyclohexanecarbonitrile selectively produced secondary amines in the presence of either Pd/C or Rh/C.
September 21, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28933042/anterior-chamber-changes-after-implantable-collamer-lens-implantation-in-high-myopia-using-pentacam-a-prospective-study
#12
Mohamed Nagy Elmohamady, Walid Abdelghaffar
INTRODUCTION: The objective of this study was to evaluate the changes of the anterior chamber (AC) of the eye after implantable Collamer lens (ICL) implantation in high myopia by using the Pentacam. METHODS: The prospective study included 34 high myopic patients (34 eyes). All patients were treated with Visian implantable Collamer lens (ICL) (Staar Surgical Co.) implantation. The Pentacam (Oculus) was used for all cases preoperatively and 1, 3 and 6 months postoperatively...
September 20, 2017: Ophthalmology and Therapy
https://www.readbyqxmd.com/read/28932839/the-fluorescence-properties-of-tiara-like-structural-thiolated-palladium-clusters
#13
Jishi Chen, Yanze Pan, Zonghua Wang, Peng Zhao
A series of tiara like structural Pdn(SR)2n (5 ≤ n ≤ 20) nanoclusters were synthesized by using a modified Brust-Schiffrin route and isolated via thin layer chromatography, and further measured using MALDI-MS. A new crystal structure of tiara like structural Pd6(SC2H4Ph)12 was determined by single-crystal X-ray crystallography. The atomic distance of PdPd increased and the Pd-S bond length decreased with the increase in the n value in the optimized structure of Pdn(SR)2n (5 ≤ n ≤ 10), which were optimized by density functional theory at the B3LYP level...
September 21, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28932643/clinical-relevance-of-tumor-infiltrating-lymphocytes-pd-l1-expression-and-correlation-with-hpv-p16-in-head-and-neck-cancer-treated-with-bio-or-chemo-radiotherapy
#14
Dan Ou, Julien Adam, Ingrid Garberis, Pierre Blanchard, France Nguyen, Antonin Levy, Odile Casiraghi, Philippe Gorphe, Ingrid Breuskin, François Janot, Stephane Temam, Jean-Yves Scoazec, Eric Deutsch, Yungan Tao
To investigate the prognostic value of tumor infiltrating lymphocytes (TILs: CD8+ and FoxP3+), and PD-L1 expression in patients with head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy combined with cisplatin (CRT) or cetuximab (BRT). Immunohistochemistry for CD8, FoxP3 was performed on pretreatment tissue samples of 77 HNSCC patients. PD-L1 results were evaluable in 38 patients. Cox regression analysis was used to analyze the correlations of these biomarkers expression with clinicopathological characteristics and treatment outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932641/response-to-first-line-chemotherapy-regimen-is-associated-with-efficacy-of-nivolumab-in-non-small-cell-lung-cancer
#15
Courèche-Guillaume Kaderbhai, Corentin Richard, Jean David Fumet, Anne Aarnink, Sandra Ortiz-Cuaran, Maurice Pérol, Pascal Foucher, Bruno Coudert, Laure Favier, Aurélie Lagrange, Emeric Limagne, Romain Boidot, Sylvain Ladoire, Michel Poudenx, Marius Ilie, Paul Hofman, Pierre Saintigny, François Ghiringhelli
Nivolumab, an anti PD-1 checkpoint inhibitor has demonstrated efficacy in metastatic non-small-cell lung cancer (NSCLC) patients after failure to standard chemotherapy. Standard chemotherapy agents could promote antitumor immune response. We thus examined whether the response to first line chemotherapy could impact on nivolumab benefit. One hundred and 15 patients with NSCLC were included in this retrospective study from 4 different French centers. Forty-three squamous cell carcinomas (SCC), and 72 non-SCC received nivolumab between 2015 and 2016 (3 mg/kg IV Q2W)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932637/muc1-c-promotes-the-suppressive-immune-microenvironment-in-non-small-cell-lung-cancer
#16
Audrey Bouillez, Dennis Adeegbe, Caining Jin, Xiufeng Hu, Ashujit Tagde, Maroof Alam, Hasan Rajabi, Kwok-Kin Wong, Donald Kufe
The cancer immune microenvironment is of importance for the effectiveness of immunotherapy; however, its dysregulation is poorly understood. The MUC1-C oncoprotein is aberrantly overexpressed in non-small cell lung cancer (NSCLC) and has been linked to the induction of PD-L1. The present work investigated the effects of targeting MUC1-C in an immuno-competent MUC1 transgenic (MUC1.Tg) mouse model. We show that Lewis Lung Carcinoma cells expressing MUC1-C (LLC/MUC1) exhibit upregulation of PD-L1 and suppression of interferon-γ (IFN-γ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932634/pd1-positive-tumor-infiltrating-lymphocytes-are-associated-with-poor-clinical-outcome-after-pulmonary-metastasectomy-for-colorectal-cancer
#17
Dagmar Kollmann, Thomas Schweiger, Stefan Schwarz, Desislava Ignatova, Yun-Tsan Chang, Gerrit Lewik, Sebastian F Schoppmann, Wolfram Hoetzenecker, Walter Klepetko, Emmanuella Guenova, Konrad Hoetzenecker
Pulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression of PD-1 and its ligands are prognostic factors in a variety of primary tumors. However, their impact on patients' outcome in the setting of PM for CRC has not been evaluated before. 53 CRC patients with pulmonary metastases receiving PM with curative intent were included in this study...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932565/unique-distribution-of-programmed-death-ligand-1-pd-l1-expression-in-east-asian-non-small-cell-lung-cancer
#18
Yunjian Pan, Difan Zheng, Yuan Li, Xu Cai, Zongli Zheng, Yan Jin, Haichuan Hu, Chao Cheng, Lei Shen, Jian Wang, Hongbin Ji, Yihua Sun, Xiaoyan Zhou, Haiquan Chen
BACKGROUND: To determine the proportion and clinical features of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer (NSCLC). METHODS: PD-L1 expression was assessed by immunohistochemistry (IHC) and tumor proportion score (TPS) with the use of PD-L1 IHC 22C3 antibody (Dako North America) in 108 surgically resected lung squamous cell carcinomas (SCC) and 221 lung adenocarcinomas (LUADs), and was correlated with clinical variables, histologic subtypes, and common driver mutations...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28932563/a-systematic-and-genome-wide-correlation-meta-analysis-of-pd-l1-expression-and-targetable-nsclc-driver-genes
#19
Jin Li, Yaoqi Chen, Xiaoshun Shi, Xiaobing Le, Fenglan Feng, Jingyi Chen, Chengzhi Zhou, Yusong Chen, Shuai Wen, Haikang Zeng, Allen M Chen, Yu Zhang
BACKGROUND: Studies have shown that the ligand of programmed cell death protein 1 (B7-H1, CD274 or PD-L1) is related to lung cancer driver genes. Although studies have examined the association between lung cancer driver gene mutations or expression and PD-L1 expression, the present studies have not been mined the correlation systematically and genome-widely. METHODS: All relevant published PD-L1 articles with driver genes data and the RNA-seq dataset from The Cancer Genome Atlas (TCGA) were analyzed...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28932425/crystal-structure-of-unsymmetrical-%C3%AE-di-imine-palladium-ii-complex-cis-arn-c-me-et-c-nar-pdcl2-ar-2-6-ipr-2c6h3
#20
Shravan Kumar Ellandula, Cosmos Opoku Amoako, Joel T Mague, Perumalreddy Chandrasekaran
The unsymmetrical α-di-imine ligand N-{2-[2,6-bis-(propan-2-yl)phenylimino]pentan-3-yl-idene}-2,6-bis-(propan-2-yl)aniline, [ArN=C(Me)-(Et)C=NAr] [Ar = 2,6-(iPr)2C6H3], (I), and the corresponding palladium complex, cis-(N-{2-[2,6-bis-(propan-2-yl)phenylimino]pentan-3-yl-idene}-2,6-bis-(propan-2-yl)aniline)di-chlor-ido-palladium(II) 1,2-di-chloro-ethane monosolvate, [PdCl2(C29H42N2)]·C2H4Cl2 or cis[PdCl2{I}], (II), have been synthesized and characterized. The crystal and mol-ecular structure of the palladium(II) complex have been established by single-crystal X-ray diffraction...
July 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
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