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https://www.readbyqxmd.com/read/28625015/crispr-cas9-mediated-lag-3-disruption-in-car-t-cells
#1
Yongping Zhang, Xingying Zhang, Chen Cheng, Wei Mu, Xiaojuan Liu, Na Li, Xiaofei Wei, Xiang Liu, Changqing Xia, Haoyi Wang
T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy. One negative regulator of Tcell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout Tand CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture...
June 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28623937/the-association-of-lipid-metabolism-relative-gene-polymorphisms-and-ischemic-stroke-in-han-and-uighur-population-of-xinjiang
#2
Yun-Hua Yue, Ling-Yun Liu, Liang Hu, You-Mei Li, Jie-Ping Mao, Xiao-Ying Yang, Na-Mu Dila
BACKGROUND: The present study is aimed to evaluate difference of lipid metabolism related gene single nucleotide polymorphisms (SNPs) with ischemic stroke (IS) in Han and Uighur population of Xinjiang, China. METHODS: Four hundred eight patients with ischemic stroke and 347 unrelated healthy individuals of age and sex matched were genotyped for Apolipoprotein A5 (ApoA5), lipoprotein lipase (LPL), Cholesteryl ester transfer protein (CETP) and low-density lipoprotein receptor (LDL-R) genes...
June 17, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28623466/increases-in-circulating-amino-acids-with-in-feed-antibiotics-correlated-with-gene-expression-of-intestinal-amino-acid-transporters-in-piglets
#3
Miao Yu, Chunlong Mu, Yuxiang Yang, Chuanjian Zhang, Yong Su, Zan Huang, Kaifan Yu, Weiyun Zhu
In-feed antibiotics have been commonly used to promote the growth performance of piglets. The antibiotics can increase protein utilization, but the underlying mechanism is largely unknown. The present study investigated the effects of in-feed antibiotics on intestinal AA transporters and receptors to test the hypothesis that the alteration of circulating AA profiles may be concomitant with the change of intestinal AA transporters and receptors. Sixteen litters of piglets at day 7 started to receive creep feed with (Antibiotic) or without (Control) antibiotic...
June 16, 2017: Amino Acids
https://www.readbyqxmd.com/read/28621702/short-duration-physical-activity-prevents-the-development-of-activity-induced-hyperalgesia-through-opioid-and-serotoninergic-mechanisms
#4
Lucas V Lima, Josimari M DeSantana, Lynn A Rasmussen, Kathleen A Sluka, Lucas Vasconcelos Lima
Regular physical activity prevents development of chronic muscle pain through modulation of central mechanisms that involve rostral ventromedial medulla (RVM). We tested if pharmacological blockade or genetic deletion of mu-opioid receptors in physically active mice modulates excitatory and inhibitory systems in the RVM in an activity-induced hyperalgesia model. We examined response frequency to mechanical stimulation of the paw, muscle withdrawal thresholds, and expression of phosphorylation of the NR1 subunit of the NMDA receptor (p-NR1) and serotonin transporter (SERT) in the RVM...
June 8, 2017: Pain
https://www.readbyqxmd.com/read/28615716/lipid-vesicles-containing-transferrin-receptor-binding-peptide-tfr-t12-and-octa-arginine-conjugate-stearyl-r8-efficiently-treat-brain-glioma-along-with-glioma-stem-cells
#5
Li-Min Mu, Ying-Zi Bu, Lei Liu, Hong-Jun Xie, Rui-Jun Ju, Jia-Shuan Wu, Fan Zeng, Yao Zhao, Jing-Ying Zhang, Wan-Liang Lu
Surgery and radiotherapy cannot fully remove brain glioma; thus, chemotherapy continues to play an important role in treatment of this illness. However, because of the restriction of the blood-brain barrier (BBB) and the regeneration of glioma stem cells, post-chemotherapy relapse usually occurs. Here, we report a potential solution to these issues that involves a type of novel multifunctional vinblastine liposomes equipped with transferrin receptor binding peptide TfR-T12 and octa-arginine conjugate stearyl-R8...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28612394/tumor-associated-with-cd70-expression-is-involved-in-promoting-tumor-migration-and-macrophage-infiltration-in-gbm
#6
Haitao Ge, Luyan Mu, Linchun Jin, Changlin Yang, Yifan Emily Chang, Yu Long, Gabriel De Leon, Loic Deleyrolle, Duane A Mitchell, Paul S Kubilis, Dunyue Lu, Jiping Qi, Yunhe Gu, Zhiguo Lin, Jianping Huang
Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment...
June 13, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28596571/the-role-of-trpc6-in-the-neuroprotection-of-calycosin-against-cerebral-ischemic-injury
#7
Chao Guo, Yongyuan Ma, Shanbo Ma, Fei Mu, Jiao Deng, Jialin Duan, Lize Xiong, Ying Yin, Yanhua Wang, Miaomaio Xi, Aidong Wen
Our previous studies have provided evidences that calycosin can protect the brain from ischemia/reperfusion injury, but its mechanisms is not fully understand. Transient receptor potential canonical 6 (TRPC6) has a critical role in promoting neuronal survival against cerebral ischemic injury. The aim of the present study is to test whether calycosin protects against cerebral ischemic injury through TRPC6-CREB pathway. In vivo, rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h and then treated with different doses of calycosin at the onset of reperfusion...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28594147/casein-kinase-1-epsilon-deletion-increases-mu-opioid-receptor-dependent-behaviors-and-binge-eating
#8
Lisa R Goldberg, Stacey L Kirkpatrick, Neema Yazdani, Kimberly P Luttik, Olga A Lacki, R Keith Babbs, David F Jenkins, W Evan Johnson, Camron D Bryant
Genetic and pharmacological studies indicate that casein kinase-1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0...
June 8, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28591157/the-impact-of-de-novo-liver-metastasis-on-clinical-outcome-in-patients-with-advanced-non-small-cell-lung-cancer
#9
Yu-Ping Chang, Yu-Mu Chen, Chien-Hao Lai, Chiung-Yu Lin, Wen-Feng Fang, Cherng-Hua Huang, Shau-Hsuan Li, Hung-Chen Chen, Chin-Chou Wang, Meng-Chih Lin
Liver metastasis has been found to affect outcome in prostate cancer and colorectal cancer, but its role in lung cancer is unclear. The current study aimed to evaluate the impact of de novo liver metastasis (DLM) on stage IV non-small cell lung cancer (NSCLC) outcomes and to examine whether tyrosine kinase inhibitors (TKI) reverse poor prognosis in patients with DLM and epidermal growth factor receptor (EGFR)-mutant NSCLC. Among 1392 newly diagnosed NSCLC patients, 490 patients with stage IV disease treated between November 2010 and March 2014 at Kaohsiung Chang Gung Memorial Hospital were included...
2017: PloS One
https://www.readbyqxmd.com/read/28590714/reaching-out-for-sensitive-evaluation-of-the-mu-opioid-receptor-in-vivo-positron-emission-tomography-imaging-of-the-agonist-11c-ah7921
#10
Waqas Rafique, Shivashankar Khanapur, Mona Milde Spilhaug, Patrick J Riss
Imaging of the mu-opioid receptor availability with PET is a pertinent challenge in Neuroscience. Both, regulation of receptor expression and occupancy by endogeneous opioids play into cognitive and behavioural phenotypes of healthy function and disease. Receptor expression in the active and inactive states can be measured using high affinity radioagonist and radioanatonist PET tracers, respectively. Occupancy assessment requires radioligands showing competitive and reversible binding with moderate affinity to the MOR, which may lead to physical extinction of the receptor specific signal in vivo...
June 7, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28590406/de-novo-transcriptome-sequencing-and-the-hypothetical-cold-response-mode-of-saussurea-involucrata-in-extreme-cold-environments
#11
Jin Li, Hailiang Liu, Wenwen Xia, Jianqiang Mu, Yujie Feng, Ruina Liu, Panyao Yan, Aiying Wang, Zhongping Lin, Yong Guo, Jianbo Zhu, Xianfeng Chen
Saussurea involucrata grows in high mountain areas covered by snow throughout the year. The temperature of this habitat can change drastically in one day. To gain a better understanding of the cold response signaling pathways and molecular metabolic reactions involved in cold stress tolerance, genome-wide transcriptional analyses were performed using RNA-Seq technologies. A total of 199,758 transcripts were assembled, producing 138,540 unigenes with 46.8 Gb clean data. Overall, 184,416 (92.32%) transcripts were successfully annotated...
June 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28574864/methadone-management-of-withdrawal-associated-with-loperamide-related-opioid-use-disorder
#12
Raphael J Leo, Muhammad A Ghazi, Kelly S Jaziri
: Loperamide hydrochloride is an over-the-counter anti-diarrheal agent, acting via mu-opioid receptor agonist effects in the intestinal myenteric plexus. Although preclinical investigations suggested that abuse liability associated with loperamide use is low, there are increasing numbers of cases reported to the US Food and Drug Administration, of abuse, dependence, and withdrawal associated with loperamide use. A case of a patient with opioid use disorder, that is, in the form of protracted loperamide excess use, requiring management of withdrawal with methadone is presented...
June 1, 2017: Journal of Addiction Medicine
https://www.readbyqxmd.com/read/28571657/transplantation-of-bone-marrow-stromal-stem-cells-overexpressing-tropomyosin-receptor-kinase-a-for-peripheral-nerve-repair
#13
Meige Zheng, Junxiu Duan, Zhendan He, Zhiwei Wang, Shuhua Mu, Zhiwen Zeng, Junle Qu, Dong Wang, Jian Zhang
BACKGROUND AIMS: Previously we reported that overexpression of tropomyosin receptor kinase A (TrkA) could improve the survival and Schwann-like cell differentiation of bone marrow stromal stem cells (BMSCs) in nerve grafts for bridging rat sciatic nerve defects. The aim of this study was to investigate how TrkA affects the efficacy of BMSCs transplantation on peripheral nerve regeneration and functional recovery. METHODS: Rat BMSCs were infected with recombinant lentiviruses to construct TrkA-overexpressing BMSCs and TrkA-shRNA-expressing BMSCs, which were then seeded in acellular nerve allografts for bridging 10-mm rat sciatic nerve defects...
May 29, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28571007/eplerenone-prevents-atrial-fibrosis-via-the-tgf-%C3%AE-signaling-pathway
#14
Lili Du, Mu Qin, Yi Yi, Xiaoqing Chen, Weifeng Jiang, Li Zhou, Daoliang Zhang, Kai Xu, Yiqing Yang, Chao Li, Yan Liu, Xu Liu, Sheng-Zhong Duan
OBJECTIVES: Eplerenone (EPL), an antagonist of the mineralocorticoid receptor, is beneficial for atrial fibrillation and atrial fibrosis. However, the underlying mechanism remains less well known. We aimed to investigate the effect of EPL on atrial fibrosis using a mouse with selective atrial fibrosis and to explore the underlying mechanisms. METHODS: EPL-treated MHC-TGFcys33ser transgenic mice that have selective atrial fibrosis (Tx+EPL mice), as well as control mice, were used for in vivo studies including histological analyses, Western blotting, and qRT-PCR studies...
June 2, 2017: Cardiology
https://www.readbyqxmd.com/read/28567065/the-psychoneuroendocrine-immunotherapy-of-cancer-historical-evolution-and-clinical-results
#15
REVIEW
Paolo Lissoni, Giusy Messina, Arianna Lissoni, Rovelli Franco
The prognosis of the neoplastic diseases depends not only on the biogenetic characteristics of cancer cells but also on the immunological response of patients, which may influence the biological features of cancer cells themselves as well as the angiogenic processes. Moreover, the immune system in vivo is under a physiological psychoneuroendocrine (PNE) regulation, mainly mediated by the brain opioid system and the pineal gland. In more detail, the anticancer immunity is stimulated by the pineal hormone melatonin (MLT) and inhibited by the opioid system, namely, through a mu-opioid receptor...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28559159/hdac-inhibitor-tsa-ameliorates-mechanical-hypersensitivity-and-potentiates-analgesic-effect-of-morphine-in-a-rat-model-of-bone-cancer-pain-by-restoring-%C3%AE-opioid-receptor-in-spinal-cord
#16
Xinran Hou, Yingqi Weng, Bihan Ouyang, Zhuofeng Ding, Zongbin Song, Wangyuan Zou, Changsheng Huang, Qulian Guo
Bone cancer pain (BCP) is a common complication with inadequate management in patients suffering from advanced cancer. Histone deacetylase inhibitors showed significant analgesic effect in multiple inflammatory and neuropathic pain models, but their effect in bone cancer pain has never been explored. In this study, we utilized a BCP rat model with intra-tibial inoculation of Walker 256 mammary gland carcinoma cells, which developed progressive mechanical hypersensitivity but not thermal hypersensitivity. Intrathecal application of trichostatin A (TSA), a classic pan-HDAC inhibitor, ameliorated tactile hypersensitivity and enhanced the analgesic effect of morphine in BCP rats...
May 27, 2017: Brain Research
https://www.readbyqxmd.com/read/28558364/structural-and-functional-correlates-of-serum-soluble-il-6-receptor-level-in-patients-with-bipolar-disorder
#17
Pei-Chi Tu, Cheng-Ta Li, Wei-Chen Lin, Mu-Hong Chen, Tung-Ping Su, Ya-Mei Bai
OBJECTIVES: Inflammation is reported to play a crucial role in the pathogenesis of bipolar disorder (BD). Higher serum levels of soluble interleukin-6 receptor (sIL-6R), which forms a ligand-receptor complex with the potent proinflammatory cytokine IL-6, have been consistently observed in patients with BD. However, the effect of sIL-6R on neural structure and function remains unclear. This study investigated the association between serum sIL-6R levels and the structural and functional connectivity (FC) of the brain in patients with BD...
April 21, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28554249/suppression-of-asparaginyl-endopeptidase-attenuates-breast-cancer-induced-bone-pain-through-inhibition-of-neurotrophin-receptors
#18
Peng Yao, Yuanyuan Ding, Zhenkai Han, Ying Mu, Tao Hong, Yongqiang Zhu, Hongxi Li
Objective Cancer-induced bone pain is a common clinical problem in breast cancer patients with bone metastasis. However, the mechanisms driving cancer-induced bone pain are poorly known. Recent studies show that a novel protease, asparaginyl endopeptidase (AEP) plays crucial roles in breast cancer metastasis and progression. We aim to determine the functions and targeted suppress of AEP in a mouse model of breast cancer-induced bone pain. Methods Breast cancer cells with AEP knocked-down or overexpression were constructed and implanted into the intramedullary space of the femur to induce pain-like behavior in mice...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28554003/opioids-and-opioid-receptors-orchestrate-wound-repair
#19
Ying Wang, Mihir Gupta, Tasneem Poonawala, Mariya Farooqui, Yunfang Li, Fei Peng, Sheldon Rao, Michael Ansonoff, John E Pintar, Kalpna Gupta
We have previously shown that topical opioids including morphine and its congeners promote healing of full thickness ischemic wounds in rats. We examined the contribution of mu opioid receptor (MOPr)-mediated healing of full thickness ischemic wounds using MOPr and delta or kappa opioid receptor knockout (KO) mice. Wound closure in the early (day 5) as well as later phases was delayed in topical morphine or PBS-treated MOPr-KO mice compared with reciprocal treatments of wounds in wild-type (WT) mice. MOPr expression was significantly upregulated at 30 min in the wound margins and colocalized with wound margins and vasculature in the epidermal and dermal layers of the skin...
May 18, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28549041/value-of-osteoblast-derived-exosomes-in-bone-diseases
#20
Min Ge, Yingzhi Wu, Ronghu Ke, Tianyi Cai, Junyi Yang, Xiongzheng Mu
PURPOSE: The authors' purpose is to reveal the value of osteoblast-derived exosomes in bone diseases. METHODS: Microvesicles from supernatants of mouse Mc3t3 were isolated by ultracentrifugation and then the authors presented the protein profile by proteomics analysis. RESULTS: The authors detected a total number of 1536 proteins by mass spectrometry and found 172 proteins overlap with bone database. The Ingenuity Pathway Analysis shows network of "Skeletal and Muscular System Development and Function, Developmental Disorder, Hereditary Disorder" and pathway about osteogenesis...
June 2017: Journal of Craniofacial Surgery
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