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https://www.readbyqxmd.com/read/29332224/phosphatidylserine-exposing-blood-and-endothelial-cells-contribute-to-the-hypercoagulable-state-in-essential-thrombocythemia-patients
#1
Dongxia Tong, Muxin Yu, Li Guo, Tao Li, Jihe Li, Valerie A Novakovic, Zengxiang Dong, Ye Tian, Junjie Kou, Yayan Bi, Jinghua Wang, Jin Zhou, Jialan Shi
The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P < 0...
January 13, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29332184/neurologic-complications-of-immune-checkpoint-inhibitors
#2
Avi Fellner, Chen Makranz, Michal Lotem, Felix Bokstein, Alisa Taliansky, Shai Rosenberg, Deborah T Blumenthal, Jacob Mandel, Suzana Fichman, Elena Kogan, Israel Steiner, Tali Siegal, Alexander Lossos, Shlomit Yust-Katz
Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment for cancer. These agents, transforming the field of oncology, are not devoid of toxicity and cause immune-related side effects which can involve any organ including the nervous system. In this study, we present 9 patients (7 men and 2 women) with neurologic complications secondary to ICPI treatment. These included meningoencephalitis, limbic encephalitis, polyradiculitis, cranial polyneuropathy, myasthenic syndrome and myositis...
January 13, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29332158/combined-sublethal-irradiation-and-agonist-anti-cd40-enhance-donor-t-cell-accumulation-and-control-of-autochthonous-murine-pancreatic-tumors
#3
Lindsay K Ward-Kavanagh, Kathleen M Kokolus, Timothy K Cooper, Aron E Lukacher, Todd D Schell
Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells...
January 13, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29332115/ultrasound-guided-transversus-abdominis-plane-block-postoperative-analgesia-in-children-with-spinal-dysraphism
#4
Eralp Çevikkalp, Koray Erbüyün, Serpil Erbüyün, Gülay Ok
Pediatric regional anesthesia is widely used to relieve postoperative pain after abdominal surgery. Commonly used techniques of regional anesthesia include lumbar epidural and caudal block. However, the use of central neuraxial blockade has limitations. It is contraindicated in patients with clotting abnormalities, spinal dysraphism with tethered cord syndrome, meningomyelocele, and following spinal surgery with instrumentation. Ultrasound guided transversus abdominis plane block is a new method of regional anesthesia that can be used in settings where central neuraxial blockade is contraindicated...
January 2018: Saudi Medical Journal
https://www.readbyqxmd.com/read/29331980/dmc1-mutation-that-causes-human-non-obstructive-azoospermia-and-premature-ovarian-insufficiency-identified-by-whole-exome-sequencing
#5
Wen-Bin He, Chao-Feng Tu, Qiang Liu, Lan-Lan Meng, Shi-Min Yuan, Ai-Xiang Luo, Fu-Sheng He, Juan Shen, Wen Li, Juan Du, Chang-Gao Zhong, Guang-Xiu Lu, Ge Lin, Li-Qing Fan, Yue-Qiu Tan
BACKGROUND: The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown. OBJECTIVE: To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family. METHODS: We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family...
January 13, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29331886/anti-cancer-effects-of-hnha-and-lenvatinib-by-the-suppression-of-emt-mediated-drug-resistance-in-cancer-stem-cells
#6
Yong Sang Lee, Seok-Mo Kim, Bup-Woo Kim, Ho Jin Chang, Soo Young Kim, Cheong Soo Park, Ki Cheong Park, Hang-Seok Chang
Anaplastic thyroid cancer (ATC) constitutes less than 2% of total thyroid cancers but accounts for 20-40% of thyroid cancer-related deaths. Cancer stem cell drug resistance represents a primary factor hindering treatment. This study aimed to develop targeted agents against thyroid malignancy, focusing on individual and synergistic effects of HNHA (histone deacetylase), lenvatinib (FGFR), and sorafenib (tyrosine kinase) inhibitors. Patients with biochemically and histologically proven papillary thyroid cancer (PTC) and ATC were included...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331804/toll-like-receptor-9-antagonist-suppresses-humoral-immunity-in-experimental-autoimmune-myasthenia-gravis
#7
Peng Zhang, Chun-Lin Yang, Ru-Tao Liu, Heng Li, Min Zhang, Na Zhang, Long-Tao Yue, Cong-Cong Wang, Ying-Chun Dou, Rui-Sheng Duan
Recent studies have demonstrated the important role of toll-like receptor 9 (TLR9) signalling in autoimmune diseases, but its role in myasthenia gravis (MG) has not been fully established. We show herein that blocking TLR9 signalling via the suppressive oligodeoxynucleotide (ODN) H154 alleviated the symptoms of experimental autoimmune myasthenia gravis (EAMG). With the downregulation of dendritic cells (DCs), TLR9 interruption reduced follicular helper T cells (Tfh) and germinal centre (GC) B cells, leading to decreased antibody production...
January 11, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29331788/curcumin-inhibits-cardiac-hypertrophy-and-improves-cardiovascular-function-via-enhanced-na-ca2-exchanger-expression-after-transverse-abdominal-aortic-constriction-in-rats
#8
Xiao-Jie Bai, Jun-Tao Hao, Jin Wang, Wei-Fang Zhang, Cai-Ping Yan, Jia-Hui Zhao, Zhi-Qing Zhao
BACKGROUND: This study tested the hypothesis that inhibition of cardiac hypertrophy and preservation of cardiac/endothelial function by the natural yellow pigment curcumin are associated with upregulated expression of Na+/Ca2+ exchanger (NCX) after transverse aortic constriction (TAC). METHODS: Male Wistar rats were subjected to TAC for 10 weeks and curcumin (50 mg/kg/day) was fed by gastric gavage during TAC. Expression of NCX and endothelial nitric oxide synthase (eNOS) was analyzed by Western blot and immunohistochemistry...
July 15, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29331727/individual-variation-in-working-memory-is-associated-with-fear-extinction-performance
#9
Daniel M Stout, Dean T Acheson, Tyler M Moore, Ruben C Gur, Dewleen G Baker, Mark A Geyer, Victoria B Risbrough
PTSD has been associated consistently with abnormalities in fear acquisition and extinction learning and retention. Fear acquisition refers to learning to discriminate between threat and safety cues. Extinction learning reflects the formation of a new inhibitory-memory that competes with a previously learned threat-related memory. Adjudicating the competition between threat memory and the new inhibitory memory during extinction may rely, in part, on cognitive processes such as working memory (WM). Despite significant shared neural circuits and signaling pathways the relationship between WM, fear acquisition, and extinction is poorly understood...
January 5, 2018: Behaviour Research and Therapy
https://www.readbyqxmd.com/read/29331665/blocking-lpa-dependent-signaling-increases-ovarian-cancer-cell-death-in-response-to-chemotherapy
#10
LeAnn C Rogers, Ryan R Davis, Naveen Said, Thomas Hollis, Larry W Daniel
The paradoxical role of reactive oxygen species in cell death versus cell survival establishes a delicate balance between chemotherapy efficacy and management of detrimental side effects. Normal proliferative signaling requires that cells remain inside a redox range that allows reversible protein oxidation to occur. Shifting the redox environment toward highly reducing or oxidizing states leads to cellular stress and cell death. Reactive oxygen species produced in response to Taxol and cisplatin treatment are necessary for effective cancer cell killing but the same ROS leads to damaging side effects in normal tissues...
January 4, 2018: Redox Biology
https://www.readbyqxmd.com/read/29331638/comparative-analysis-of-membrane-protein-structure-databases
#11
REVIEW
Kentaro Shimizu, Wei Cao, Gull Saad, Michiru Shoji, Tohru Terada
BACKGROUND: Membrane proteins play important roles in cell survival and cell communication, as they function as transporters, receptors, anchors and enzymes. They are also potential targets for drugs that block receptors or inhibit enzymes related to diseases. Although the number of known structures of membrane proteins is still small relative to the size of the proteome as a whole, many new membrane protein structures have been determined recently. SCOPE OF THE ARTICLE: We compared and analyzed the widely used membrane protein databases, mpstruc, Orientations of Proteins in Membranes(OPM), and PDBTM, as well as the extended dataset of mpstruc based on sequence similarity, the PDB structures whose classification field indicates that they are "membrane proteins" and the proteins with Structural Classification of Proteins (SCOP) class-f domains...
January 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29331635/sotatercept-with-long-term-extension-for-the-treatment-of-anaemia-in-patients-with-lower-risk-myelodysplastic-syndromes-a-phase-2-dose-ranging-trial
#12
Rami Komrokji, Guillermo Garcia-Manero, Lionel Ades, Thomas Prebet, David P Steensma, Joseph G Jurcic, Mikkael A Sekeres, Jesus Berdeja, Michael R Savona, Odile Beyne-Rauzy, Aspasia Stamatoullas, Amy E DeZern, Jacques Delaunay, Gautam Borthakur, Robert Rifkin, Thomas E Boyd, Abderrhamane Laadem, Bond Vo, Jennie Zhang, Marie Puccio-Pick, Kenneth M Attie, Pierre Fenaux, Alan F List
BACKGROUND: Myelodysplastic syndromes are characterised by ineffective erythropoiesis leading to anaemia. Sotatercept (ACE-011) is a novel activin receptor type IIA fusion protein that acts as a ligand trap to neutralise negative regulators of late-stage erythropoiesis. The aim of the study was to establish a safe and effective dose of sotatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes. METHODS: This open-label, multicentre, dose-ranging, phase 2 trial took place at 11 treatment centres in the USA and France...
January 10, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29331583/importins-%C3%AE-and-%C3%AE-signaling-mediates-endothelial-cell-inflammation-and-barrier-disruption
#13
Antony Leonard, Arshad Rahman, Fabeha Fazal
Nucleocytoplasmic shuttling via importins is central to the function of eukaryotic cells and an integral part of the processes that lead to many human diseases. In this study, we addressed the role of α and β importins in the mechanism of endothelial cell (EC) inflammation and permeability, important pathogenic features of many inflammatory diseases such as acute lung injury and atherosclerosis. RNAi-mediated knockdown of importin α4 or α3 each inhibited NF-κB activation, proinflammatory gene (ICAM-1, VCAM-1, and IL-6) expression, and thereby endothelial adhesivity towards HL-60 cells, upon thrombin challenge...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29331464/somatic-cell-count-based-selection-reduces-susceptibility-to-energy-shortage-during-early-lactation-in-a-sheep-model
#14
J Bouvier-Muller, C Allain, F Enjalbert, Y Farizon, D Portes, G Foucras, R Rupp
During the transition from late gestation to early lactation ruminants experience a negative energy balance (NEB), which is considered to increase susceptibility to mammary infections. Our previous study in 2 divergent lines of sheep selected for high and low somatic cell score (SCS) suggested an association between the response to NEB and genetic susceptibility to mastitis. Forty-eight early-lactation primiparous dairy ewes from the 2 SCS genetic lines were allocated to 2 homogeneous subgroups-an NEB group, which was energy restricted and received 60% of the energy requirements for 15 d, and a control-fed group-to obtain 4 balanced groups of 12 ewes: high-SCS positive energy balance, low-SCS positive energy balance, high-SCS NEB, and low-SCS NEB...
January 10, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29331425/low-picomolar-label-free-procalcitonin-analytical-detection-with-an-electrolyte-gated-organic-field-effect-transistor-based-electronic-immunosensor
#15
Preethi Seshadri, Kyriaki Manoli, Nicole Schneiderhan-Marra, Uwe Anthes, Piotr Wierzchowiec, Klaus Bonrad, Cinzia Di Franco, Luisa Torsi
Herein a label-free immunosensor based on electrolyte-gated organic field-effect transistor (EGOFET) was developed for the detection of procalcitonin (PCT), a sepsis marker. Antibodies specific to PCT were immobilized on the poly-3-hexylthiophene (P3HT) organic semiconductor surface through direct physical adsorption followed by a post-treatment with bovine serum albumin (BSA) which served as the blocking agent to prevent non-specific adsorption. Antibodies together with BSA (forming the whole biorecognition layer) served to selectively capture the procalcitonin target analyte...
December 26, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29331421/hyperglycaemia-induced-mir-301a-promotes-cell-proliferation-by-repressing-p21-and-smad4-in-prostate-cancer
#16
Xiaojuan Li, Jun Li, Yi Cai, Shubin Peng, Jun Wang, Zhaoming Xiao, Yu Wang, Yiran Tao, Jun Li, Qu Leng, Dinglan Wu, Shaodong Yang, Ziliang Ji, Yuefu Han, Liren Li, Xin Gao, Chunxian Zeng, Xingqiao Wen
Hyperglycaemia promotes the development of Prostate cancer (PCa). However, the roles of miRNAs in this disease process and the underlying mechanisms are largely unknown. In this study, we recruited 391 PCa patients in China and found that PCa patients with high level blood glucose (≥100 mg/dL) trended to have high Gleason score (GS≥7). miRNA-301a levels were significantly higher in prostate cancer than that in normal prostate tissues. Hyperglycaemia or high glucose treatment induced miR-301a expression in prostate tissues or PCa cell lines...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29331416/deubiquitinating-enzyme-psmd14-promotes-tumor-metastasis-through-stabilizing-snail-in-human-esophageal-squamous-cell-carcinoma
#17
Rui Zhu, Yongshuo Liu, Honghong Zhou, Lei Li, Yi Li, Fang Ding, Xiufeng Cao, Zhihua Liu
The epithelial-mesenchymal transition (EMT) transcription factor SNAIL is associated with distant metastasis and poor prognosis of esophageal squamous cell carcinoma (ESCC) patients. The proteolysis of SNAIL is mediated by the ubiquitin-proteasome system. Several E3 ligases have been characterized to promote SNAIL ubiquitination and degradation. However, the reverse process - deubiquitination of SNAIL remains largely unknown. In this study, we performed a mass spectrometry to examine the interaction between SNAIL and deubiquitinating enzyme(s)...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29331229/hominin-raw-material-procurement-in-the-oldowan-acheulean-transition-at-olduvai-gorge
#18
Lindsay J McHenry, Ignacio de la Torre
The lithic assemblages at the Oldowan-Acheulean transition in Bed II of Olduvai Gorge, Tanzania, represent a wide variety of raw materials reflecting both the diversity of volcanic, metamorphic, and sedimentary source materials available in the Olduvai basin and surroundings and the preferences of the tool-makers. A geochemical and petrographic systematic analysis of lava-derived archaeological stone tools, combined with textural and mineralogical characterization of quartzite, chert, and other metamorphic and sedimentary raw materials from two Middle and Upper Bed II sites, has enabled us to produce a comprehensive dataset and characterization of the rocks employed by Olduvai hominins, which is used here to establish a referential framework for future studies on Early Stone Age raw material provenancing...
January 10, 2018: Journal of Human Evolution
https://www.readbyqxmd.com/read/29330972/immunohistochemical-evaluation-of-oestrogen-receptors-in-adenoid-cystic-carcinoma-of-salivary-gland
#19
Hasan Mujtaba, Muhammad Atique, Iffat Batool, Muhammad Farooq Umer
Background: Oestrogen has a physiological role throughout the body including oral cavity. The effects are mediated by binding to two receptors in nucleus alpha and beta, which are ligand-activated transcription factors. The alpha receptors have a prognostic significance in cancer of breast while in Adenoid cystic carcinoma of salivary glands the results are inconsistent. This study was conducted to determine the oestrogen receptor Alpha staining in adenoid cystic carcinoma of salivary gland...
October 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/29330958/do-muscles-constrain-skull-shape-evolution-in-strepsirrhines
#20
Anne-Claire Fabre, Jonathan M G Perry, Adam Hartstone-Rose, AuróLien Lowie, Andy Boens, MaÏtena Dumont
Despite great interest and decades of research, the musculoskeletal relationships of the masticatory system in primates are still not fully understood. However, without a clear understanding of the interplay between muscles and bones it remains difficult to understand the functional significance of morphological traits of the skeleton. Here, we aim to study the impacts of the masticatory muscles on the shape of the cranium and the mandible as well as their co-variation in strepsirrhine primates. To do so, we use 3D geometric morphometric approaches to assess the shape of each bone of the skull of 20 species for which muscle data are available in the literature...
February 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
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