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https://www.readbyqxmd.com/read/29661736/loss-of-pd-l1-sp-142-expression-characterizes-renal-vein-tumor-thrombus-microenvironment-in-clear-cell-renal-cell-carcinoma
#1
José I López, Rafael Pulido, Charles H Lawrie, Javier C Angulo
Immunotherapy is a promising tool in the treatment of patients with advancer renal cancer, in particular the blockage of immune checkpoint inhibitors. Clear cell renal cell carcinoma is an example of heterogeneous neoplasm and this particular characteristic is responsible of many therapeutic failures so far. Since variations in the local microenvironment across a tumor may conditionate the effect of this new therapy, a deeper knowledge of this issue seems advisable for any treatment success. We have analyzed the PD-L1 (SP142) expression in three different areas in the tumor and in two areas in the renal vein/caval thrombi in 39 advanced clear cell renal cell carcinomas to determine the extent and potential clinical significance of this regional variability...
March 24, 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29648983/enhancement-of-brain-d-serine-mediates-recovery-of-cognitive-function-after-tbi
#2
Sigal Liraz-Zaltsman, Barbara Slusher, Dana Atrakchi-Baranes, Kinneret Rosenblatt, Yael Friedman Levi, Efrat Leah Kesner, Alcino J Silva, Anat Biegon, Esther Shohami
Cognitive deficits, especially memory loss, are common and devastating neuropsychiatric sequelae of traumatic brain injury (TBI). The deficits may persist for a long time and may be accompanied by increased risk of developing early onset dementia. Past attempts to reverse the neuropsychological effects of brain injury with glutamate-N-methyl-D-aspartate (NMDA) antagonists failed to show any benefits or worsened the outcome, suggesting activation, rather than blockage, of the NMDA receptor (NMDAR) may be useful in the sub-acute period after TBI and stroke...
March 14, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29550457/the-status-of-provision-of-post-abortion-care-services-for-women-and-girls-in-eastern-and-southern-africa-a-systematic-review
#3
REVIEW
Carolien J Aantjes, Andrew Gilmoor, Elena V Syurina, Tamaryn L Crankshaw
OBJECTIVE: To conduct a systematic review of the status of post-abortion care (PAC) provision in Eastern and Southern Africa with particular reference to reach, quality and costs of these services. STUDY DESIGN: We searched Pubmed, EMBASE, Science Direct, POPLINE and Web of Science for articles published between 2000 and October 2017 presenting primary or secondary data from one or more countries in the region. RESULTS: Seventy articles representing data from fourteen countries were abstracted and included in the review...
March 14, 2018: Contraception
https://www.readbyqxmd.com/read/29501898/modified-eversion-carotid-endarterectomy-a-14-years-experience-in-a-tertiary-teaching-university-hospital-in-brazil-south-america
#4
Fábio Hüsemann/Menezes, Natália Ponzio/Pagliuso, Giovani José Dal Poggetto/Molinari
INTRODUCTION: Carotid endarterectomy is one of the most performed vascular procedures. Since the first reports in the late 1950's the conventional open and the eversion techniques are the popularized ones. A short extraction or partial eversion technique has been previously described and recently has been subject to case-series reports. OBJECTIVE: to present the experience of a teaching hospital with modified or partial eversion endarterectomy compared to the conventional open procedure, performed exclusively by training vascular surgeons...
March 1, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29484736/pharmacological-or-transcriptional-inhibition-of-both-hdac1-and-2-leads-to-cell-cycle-blockage-and-apoptosis-via-p21-waf1-cip1-and-p19-ink4d-upregulation-in-hepatocellular-carcinoma
#5
Hengyu Zhou, Ying Cai, Dina Liu, Menghui Li, Yu Sha, Wenlu Zhang, Kai Wang, Jianping Gong, Ni Tang, Ailong Huang, Jie Xia
OBJECTIVES: Histone deacetylases (HDACs) are commonly dysregulated in cancer and represent promising therapeutic targets. However, global HDAC inhibitors have shown limited efficacy in the treatment of solid tumours, including hepatocellular carcinoma (HCC). In this study, we investigated the therapeutic effect of selectively inhibiting HDAC1 and 2 in HCC. METHODS: HDAC1 inhibitor Tacedinaline (CI994), HDAC2 inhibitor Santacruzamate A (CAY10683), HDAC1/2 common inhibitor Romidepsin (FK228) and global HDAC inhibitor Vorinostat (SAHA) were used to treat HCC cells...
February 27, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29464191/impact-of-nmda-receptor-overexpression-on-cerebellar-purkinje-cell-activity-and-motor-learning
#6
Elisa Galliano, Martijn Schonewille, Saša Peter, Mandy Rutteman, Simone Houtman, Dick Jaarsma, Freek E Hoebeek, Chris I De Zeeuw
In many brain regions involved in learning NMDA receptors (NMDARs) act as coincidence detectors of pre- and postsynaptic activity, mediating Hebbian plasticity. Intriguingly, the parallel fiber (PF) to Purkinje cell (PC) input in the cerebellar cortex, which is critical for procedural learning, shows virtually no postsynaptic NMDARs. Why is this? Here, we address this question by generating and testing independent transgenic lines that overexpress NMDAR containing the type 2B subunit (NR2B) specifically in PCs...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29425229/schistosoma-mansoni-smki-1-serine-protease-inhibitor-binds-to-elastase-and-impairs-neutrophil-function-and-inflammation
#7
Suellen B Morais, Barbara C Figueiredo, Natan R G Assis, Debora M Alvarenga, Mariana T Q de Magalhães, Rafaela S Ferreira, Angélica T Vieira, Gustavo B Menezes, Sergio C Oliveira
Protease inhibitors have important function during homeostasis, inflammation and tissue injury. In this study, we described the role of Schistosoma mansoni SmKI-1 serine protease inhibitor in parasite development and as a molecule capable of regulating different models of inflammatory diseases. First, we determine that recombinant (r) SmKI-1 and its Kunitz domain but not the C-terminal region possess inhibitory activity against trypsin and neutrophil elastase (NE). To better understand the molecular basis of NE inhibition by SmKI-1, molecular docking studies were also conducted...
February 9, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29408381/autophosphorylation-is-a-mechanism-of-inhibition-in-twitchin-kinase
#8
Rhys M Williams, Barbara Franke, Mark Wilkinson, Jennifer R Fleming, Daniel J Rigden, Guy M Benian, Patrick A Eyers, Olga Mayans
Titin-like kinases are muscle-specific kinases that regulate mechanical sensing in the sarcomere. Twitchin kinase (TwcK) is the best-characterized member of this family, both structurally and enzymatically. TwcK activity is auto-inhibited by a dual intrasteric mechanism, in which N- and C-terminal tail extensions wrap around the kinase domain, blocking the hinge region, the ATP binding pocket and the peptide substrate binding groove. Physiologically, kinase activation is thought to occur by a stretch-induced displacement of the inhibitory tails from the kinase domain...
February 3, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29395786/an-intramolecular-interaction-of-uhrf1-reveals-dual-control-for-its-histone-association
#9
Linfeng Gao, Xiao-Feng Tan, Shen Zhang, Tianchen Wu, Zhi-Min Zhang, Hui-Wang Ai, Jikui Song
UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) is one of the essential components of mammalian DNA methylation machinery. Chromatin association of UHRF1 is controlled via an interplay between its intramolecular interaction and dual recognition of histone H3 trimethylated at lysine 9 (H3K9me3) and hemimethylated DNA. Here, we report the crystal structure of the N-terminal tandem Tudor domain (TTD) of UHRF1 in complex with the C-terminal polybasic region (PBR). Structural analysis reveals that PBR binding leads to displacement of the TTD-plant homeodomain (PHD) linker, as well as blockage of the H3K9me3-engaging cage, both of which contribute to a chromatin-occluded UHRF1 conformation...
January 18, 2018: Structure
https://www.readbyqxmd.com/read/29343773/mitochondrial-mutations-in-cholestatic-liver-disease-with-biliary-atresia
#10
Hong Koh, Gun-Seok Park, Sun-Mi Shin, Chang Eon Park, Seung Kim, Seok Joo Han, Huy Quang Pham, Jae-Ho Shin, Dong-Woo Lee
Biliary atresia (BA) results in severe bile blockage and is caused by the absence of extrahepatic ducts. Even after successful hepatic portoenterostomy, a considerable number of patients are likely to show progressive deterioration in liver function. Recent studies show that mutations in protein-coding mitochondrial DNA (mtDNA) genes and/or mitochondrial genes in nuclear DNA (nDNA) are associated with hepatocellular dysfunction. This observation led us to investigate whether hepatic dysfunctions in BA is genetically associated with mtDNA mutations...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343555/antagonism-of-integrin-cd11b-affords-protection-against-endotoxin-shock-and-polymicrobial-sepsis-via-attenuation-of-hmgb1-nucleocytoplasmic-translocation-and-extracellular-release
#11
Huiting Zhou, Yanhong Li, Huan Gui, He Zhao, Ming Wu, Gang Li, Yiping Li, Zhenjiang Bai, Zhimin Yin, H Paul Redmond, Jian Wang, Jiang Huai Wang, Zhihui Zhao
High mobility group box 1 (HMGB1), a chromatin-binding nuclear protein, plays a critical role in sepsis by acting as a key "late-phase" inflammatory mediator. Integrin CD11b is essential for inflammatory cell activation and migration, thus mediating inflammatory responses. However, it is unclear whether CD11b participates in the development of sepsis. In this study, we report that CD11b contributes to LPS-induced endotoxin shock and microbial sepsis, as antagonism of CD11b with the CD11b blocking Ab or CD11b inhibitor Gu-4 protects mice against LPS- and microbial sepsis-related lethality, which is associated with significantly diminished serum HMGB1 levels...
January 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29303789/sevoflurane-blocks-the-induction-of-long-term-potentiation-when-present-during-but-not-when-present-only-before-the-high-frequency-stimulation
#12
Jinyang Liu, Lie Yang, Daisy Lin, James E Cottrell, Ira S Kass
BACKGROUND: This study tests the hypothesis that sevoflurane blocks long-term potentiation only if it is present during the high-frequency stimulation that induces long-term potentiation. METHODS: Long-term potentiation, an electrophysiologic correlate of memory, was induced by high-frequency stimulation and measured as a persistent increase in the field excitatory postsynaptic potential slope in the CA1 region. RESULTS: Long-term potentiation was induced in the no sevoflurane group (171 ± 58% vs...
March 2018: Anesthesiology
https://www.readbyqxmd.com/read/29290065/pathophysiology-of-primary-open-angle-glaucoma-from-a-neuroinflammatory-and-neurotoxicity-perspective-a-review-of-the-literature
#13
REVIEW
Karine Evangelho, Maria Mogilevskaya, Monica Losada-Barragan, Jeinny Karina Vargas-Sanchez
PURPOSE: Glaucoma is the leading cause of blindness in humans, affecting 2% of the population. This disorder can be classified into various types including primary, secondary, glaucoma with angle closure and with open angle. The prevalence of distinct types of glaucoma differs for each particular region of the world. One of the most common types of this disease is primary open-angle glaucoma (POAG), which is a complex inherited disorder characterized by progressive retinal ganglion cell death, optic nerve head excavation and visual field loss...
December 30, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/29284890/a-safe-regional-technique-in-a-high-risk-patient-cervical-plexus-blockage
#14
Ayhan Kaydu, Ebru Tarıkçı Kılıç, Erhan Gökçek, Mehmet Salim Akdemir
Regional anesthesia in the form of combined cervical plexus block is gaining popularity as a technique of choice for cervical spine surgeries, especially for urgent ones. An important advantage is that it allows continuous monitoring of patient's neurological status. The success of the block often depends on accurate placement of the local anesthetic. Landmarks for the block are therefore of great importance. In this case, we aimed to present a 74-year-old man with C4-5 odontoid fracture. We planned to perform a unilateral combined cervical plexus block for anterior cervical instrumentation and fusion (ACIF) operation because of his associated high-risk comorbid disorders...
October 2017: Anesthesia, Essays and Researches
https://www.readbyqxmd.com/read/29275014/development-of-a-reactive-oxygen-species-sensitive-nitric-oxide-synthase-inhibitor-for-the-treatment-of-ischemic-stroke
#15
Kevin M Nash, Isaac T Schiefer, Zahoor A Shah
Ischemic stroke is caused by a blockage of cerebral blood flow resulting in neuronal and glial hypoxia leading to inflammatory and reactive oxygen species (ROS)-mediated cell death. Nitric oxide (NO) formed by NO synthase (NOS) is known to be protective in ischemic stroke, however NOS has been shown to 'uncouple' under oxidative conditions to instead produce ROS. Nitrones are antioxidant molecules that are shown to trap ROS to then decompose and release NO. In this study, the nitrone 5 was designed such that its decomposition product is a NOS inhibitor, 6, effectively leading to NOS inhibition specifically at the site of ROS production...
February 1, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29190367/early-experience-with-bilateral-continuous-femoral-nerve-block-and-single-injection-spinal-anesthesia-for-bilateral-total-knee-arthroplasty-a-case-series
#16
Matthew R Patrick, Hari K Parvataneni, Donald S Bohannon, André P Boezaart
Objective: Total knee arthroplasty (TKA) is a commonly performed surgery in the United States, with demand for unilateral and simultaneous bilateral TKAs (BTKAs) expected to increase significantly over the coming decades. This study reports the authors' early experience in a consecutive series of simultaneous BTKAs performed under regional anesthesia and mild sedation. Methods: In this retrospective case series, the authors examined all simultaneous BTKAs performed over two years by a single surgeon...
November 28, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29133885/a-conserved-stem-of-the-myxococcus-xanthus-srna-pxr-controls-srna-accumulation-and-multicellular-development
#17
Yuen-Tsu N Yu, Elizabeth Cooper, Gregory J Velicer
The small RNA (sRNA) Pxr negatively controls multicellular fruiting body formation in the bacterium Myxococcus xanthus, inhibiting the transition from growth to development when nutrients are abundant. Like many other prokaryotic sRNAs, Pxr is predicted to fold into three stem loops (SL1-SL3). SL1 and SL2 are highly conserved across the myxobacteria, whereas SL3 is much more variable. SL1 is necessary for the regulatory function of Pxr but the importance of SL3 in this regard is unknown. To test for cis genetic elements required for Pxr function, we deleted the entire pxr gene from a developmentally defective strain that fails to remove Pxr-mediated blockage of development and reintroduced variably truncated fragments of the pxr region to test for their ability to block development...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29120327/capillary-pericytes-mediate-coronary-no-reflow-after-myocardial-ischaemia
#18
Fergus M O'Farrell, Svetlana Mastitskaya, Matthew Hammond-Haley, Felipe Freitas, Wen Rui Wah, David Attwell
After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic 'no-reflow' has been attributed to capillary constriction by contractile pericytes. We now show that occlusion of a rat coronary artery, followed by reperfusion, blocks 40% of cardiac capillaries and halves perfused blood volume within the affected region. Capillary blockages colocalised strongly with pericytes, where capillary diameter was reduced by 37%...
November 9, 2017: ELife
https://www.readbyqxmd.com/read/29118763/induction-of-antihuman-c-c-chemokine-receptor-type-5-antibodies-by-a-bovine-herpesvirus-type-4-based-vector
#19
Andrea Elizabeth Verna, Valentina Franceschi, Giulia Tebaldi, Francesca Macchi, Valentina Menozzi, Claudia Pastori, Lucia Lopalco, Simone Ottonello, Sandro Cavirani, Gaetano Donofrio
Bovine herpesvirus 4 (BoHV-4) is a promising vector for the delivery and intracellular expression of recombinant antigens and can thus be considered as a new prototype vaccine formulation system. An interesting, and actively pursued, antigen in the context of human immunodeficiency virus (HIV) infection prophylaxis (and therapy) is the C-C chemokine receptor type 5 (CCR5) co-receptor, whose blockage by specific antibodies has been shown to inhibit both viral entry and cell-to-cell transmission of the virus...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29091896/effect-of-the-nadph-oxidase-inhibitor-apocynin-on-ischemia-reperfusion-hippocampus-injury-in-rat-brain
#20
Monika Kapoor, Neha Sharma, Rajat Sandhir, Bimla Nehru
Blockage along with sudden restoration of blood following ischemia, results in several cascading events, such as a massive ROS production which plays an important role in the pathophysiology of ischemia. NADPH oxidase complex in mitochondria complex is believed to be the major source for ROS production. The present study explores the therapeutic potential of apocynin, an NADPH oxidase inhibitor in attenuating the ROS production, and the resultant neuroinflammation and mitochondrial injury during cerebral ischemia in rats...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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