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https://www.readbyqxmd.com/read/28237965/genetic-dissection-of-anterior-segment-dysgenesis-caused-by-a-col4a1-mutation
#1
Mao Mao, Márton Kiss, Yvonne Ou, Douglas B Gould
Ocular anterior segment dysgenesis (ASD) describes a spectrum of clinically and genetically heterogeneous congenital disorders affecting anterior structures that often lead to impaired vision. More importantly, between 50-75% of patients with ASD develop early onset and aggressive glaucoma. Although several genes have been implicated in the etiology of ASD, the underlying mechanisms remain elusive. Type IV collagen alpha 1 (COL4A1) is an extracellular matrix protein and a critical component of nearly all basement membranes...
February 24, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28230773/programmed-death-ligand-1-pd-l1-tumor-expression-is-associated-with-a-better-prognosis-and-diabetic-disease-in-triple-negative-breast-cancer-patients
#2
Gerardo Botti, Francesca Collina, Giosuè Scognamiglio, Federica Rao, Valentina Peluso, Rossella De Cecio, Michela Piezzo, Gabriella Landi, Michelino De Laurentiis, Monica Cantile, Maurizio Di Bonito
Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28229168/cd14-cd16-nonclassical-monocytes-are-associated-with-endothelial-dysfunction-in-patients-with-coronary-artery-disease
#3
Karol Urbanski, Dominik Ludew, Grzegorz Filip, Magdalena Filip, Agnieszka Sagan, Piotr Szczepaniak, Grzegorz Grudzien, Jerzy Sadowski, Barbara Jasiewicz-Honkisz, Tomasz Sliwa, Boguslaw Kapelak, Eilidh McGinnigle, Tomasz Mikolajczyk, Tomasz J Guzik
Endothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14(++)CD16(-) "classical - Mon1", CD14(++)CD16(+) "intermediate - Mon2" and CD14(+)CD16(++) "nonclassical - Mon3"), endothelial function and risk factor profiles in 130 patients with CAD undergoing coronary artery bypass grafting...
February 23, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28220199/-novel-pharmaceutical-treatment-approaches-for-gastric-cancer
#4
F Lordick
This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging...
February 20, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28218355/mechanisms-of-endothelial-activation-in-sepsis-and-cell-culture-models-to-study-the-heterogeneous-host-response
#5
Tanja Eichhorn, Michael B Fischer, Viktoria Weber
Sepsis is currently viewed as a fundamental disintegration of control functions from intracellular signalling to immunoregulatory and neuroendocrine mechanisms. The immediate threat in sepsis is invasive infection, and the need to activate immune defense mechanisms to clear the pathogen before irreparable damage occurs. In the process of pathogen elimination, however, the systemic host response to infection may cause collateral damage to the endothelium and may lead to the destruction of host tissues.A number of experimental models have been developed to monitor endothelial activation and to study endothelial dysfunction under septic conditions...
February 13, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28216514/diallyl-trisulfide-augments-ischemia-induced-angiogenesis-via-an-endothelial-nitric-oxide-synthase-dependent-mechanism
#6
Ryo Hayashida, Kazuhisa Kondo, Sumio Morita, Kazumasa Unno, Satoshi Shintani, Yuuki Shimizu, John W Calvert, Rei Shibata, Toyoaki Murohara
BACKGROUND: Hydrogen sulfide (H2S) exerts beneficial actions against the development of cardiovascular disease. Diallyl trisulfide (DATS) is an organic polysulfide found in garlic oil that liberates H2S under physiological conditions. This study investigated whether DATS modulates endothelial cell function, as well as revascularization processes in a mouse model of hind-limb ischemia.Methods and Results:Wild-type (WT), endothelial nitric oxide synthase-deficient (eNOS-KO) and Akt1-heterogenic deficient (Akt-Het) mice were subjected to unilateral hindlimb ischemia (HLI)...
February 17, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28216374/yin-yang-effect-of-tumor-infiltrating-b-cells-in-breast-cancer-from-mechanism-to-immunotherapy
#7
Zhigang Zhang, Ying Zhu, Zhen Wang, Ting Zhang, Pin Wu, Jian Huang
Breast cancer cells secrete chemokines, such as CXCL13, and antigens or express high endothelial venules, attracting B cells to infiltrate into the tumor microenvironment and play a "yin-yang" effect. They not only enhance the anti-tumor immune effect via secreting antibodies and influencing the Fas/FasL, CXCR4/CXCL12 and perforin pathways but they also promote the tumor to form a suppressive milieu by producing immunomodulatory factors and cytokines or using cell-to-cell education to induce the generation of Tregs or myeloid-derived suppressor cells (MDSCs)...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28216298/cell-instructive-starpeg-heparin-collagen-composite-matrices
#8
Marcus Binner, Laura J Bray, Jens Friedrichs, Uwe Freudenberg, Mikhail V Tsurkan, Carsten Werner
: Polymer hydrogels can be readily modulated with regard to their physical properties and functionalized to recapitulate molecular cues of the extracellular matrix (ECM). However, they remain structurally different from the hierarchical supramolecular assemblies of natural ECM. Accordingly, we herein report a set of hydrogel composite materials made from starPEG-peptide conjugates, maleimide-functionalized heparin and collagen type I that combine semisynthetic and ECM-derived components...
February 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28208166/incidence-and-visual-outcomes-of-culture-proven-endophthalmitis-following-dexamethasone-intravitreal-implant
#9
Maxwell S Stem, Bozho Todorich, Yoshihiro Yonekawa, Antonio Capone, George A Williams, Alan J Ruby
Importance: The rate of endophthalmitis following dexamethasone intravitreal implant (DEX) has varied in large clinical trials. Furthermore, to our knowledge, the optimal management of eyes with endophthalmitis associated with DEX has not been established. Objective: To report the incidence of culture-proven endophthalmitis in a single vitreoretinal practice over the course of 3 years and describe the clinical outcomes associated with each case of endophthalmitis...
February 16, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28205564/elevated-serum-interferon-%C3%AE-induced-protein-10-kda-is-associated-with-tafro-syndrome
#10
Noriko Iwaki, Yuka Gion, Eisei Kondo, Mitsuhiro Kawano, Taro Masunari, Hiroshi Moro, Koji Nikkuni, Kazue Takai, Masao Hagihara, Yuko Hashimoto, Kenji Yokota, Masataka Okamoto, Shinji Nakao, Tadashi Yoshino, Yasuharu Sato
Multicentric Castleman disease (MCD) is a heterogeneous lymphoproliferative disorder. It is characterized by inflammatory symptoms, and interleukin (IL)-6 contributes to the disease pathogenesis. Human herpesvirus 8 (HHV-8) often drives hypercytokinemia in MCD, although the etiology of HHV-8-negative MCD is idiopathic (iMCD). A distinct subtype of iMCD that shares a constellation of clinical features including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been reported as TAFRO-iMCD, however the differences in cytokine profiles between TAFRO-iMCD and iMCD have not been established...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28190431/posterior-reversible-encephalopathy-in-the-intensive-care-unit
#11
M Toledano, J E Fugate
Posterior reversible encephalopathy syndrome (PRES) is increasingly diagnosed in the emergency department, and medical and surgical intensive care units. PRES is characterized by acute onset of neurologic symptoms in the setting of blood pressure fluctuations, eclampsia, autoimmune disease, transplantation, renal failure, or exposure to immunosuppressive or cytotoxic drugs, triggers known to admit patients to the intensive care unit (ICU). Although the exact pathophysiology remains unknown, there is growing consensus that PRES results from endothelial dysfunction...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28183278/a-rare-case-of-renal-thrombotic-microangiopathy-associated-with-castleman-s-disease
#12
Anubha Mutneja, L Nicholas Cossey, Helen Liapis, Ying Maggie Chen
BACKGROUND: Castleman's disease (CD) is an uncommon, heterogeneous lympho-proliferative disorder leading to high circulating levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). Renal involvement has been only described in a limited number of small studies. Herein, we report a rare case of renal thrombotic microangiopathy (TMA) associated with CD and investigate the podocyte expression of VEGF in the renal biopsy prior to initiation of treatment. CASE PRESENTATION: An 18-year-old male presented with fever, diarrhea, diffuse lymphadenopathy, ascites and acute kidney injury...
February 10, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28183139/cancer-treatment-scheduling-and-dynamic-heterogeneity-in-social-dilemmas-of-tumour-acidity-and-vasculature
#13
Artem Kaznatcheev, Robert Vander Velde, Jacob G Scott, David Basanta
BACKGROUND: Tumours are diverse ecosystems with persistent heterogeneity in various cancer hallmarks like self-sufficiency of growth factor production for angiogenesis and reprogramming of energy metabolism for aerobic glycolysis. This heterogeneity has consequences for diagnosis, treatment and disease progression. METHODS: We introduce the double goods game to study the dynamics of these traits using evolutionary game theory. We model glycolytic acid production as a public good for all tumour cells and oxygen from vascularisation via vascular endothelial growth factor production as a club good benefiting non-glycolytic tumour cells...
February 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28170195/are-mesenchymal-stem-cells-so-bloody-great-after-all
#14
Stephanie J Marfy-Smith, Claire E Clarkin
This Perspective discusses some activities of mesenchymal stem cells (MSCs) in the context of angiogenesis, focusing on contrasting effects that could call into question the extent to which MSCs can be used clinically in the future. We report on the antiangiogenic/antiproliferative effects of specific MSC populations (including bone marrow MSCs), their paracrine activity, tissue heterogeneity, and endothelial cell interactions. Also discussed are what could lead to contrasting effects of the influence of MSCs in regulating angiogenesis, pointing to some negative effects of these cells...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28170183/functional-human-and-murine-tissue-engineered-liver-is-generated-from-adult-stem-progenitor-cells
#15
Nirmala Mavila, Andrew Trecartin, Ryan Spurrier, Yi Xiao, Xiaogang Hou, David James, Xiaowei Fu, Brian Truong, Clara Wang, Gerald S Lipshutz, Kasper S Wang, Tracy C Grikscheit
Liver disease affects large numbers of patients, yet there are limited treatments available to replace absent or ineffective cellular function of this crucial organ. Donor scarcity and the necessity for immunosuppression limit one effective therapy, orthotopic liver transplantation. But in some conditions such as inborn errors of metabolism or transient states of liver insufficiency, patients may be salvaged by providing partial quantities of functional liver tissue. After transplanting multicellular liver organoid units composed of a heterogeneous cellular population that includes adult stem and progenitor cells, both mouse and human tissue-engineered liver (TELi) form in vivo...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28165469/notch3-signaling-mediated-melanoma-endothelial-crosstalk-regulates-melanoma-stem-like-cell-homeostasis-and-niche-morphogenesis
#16
Mei-Yu Hsu, Moon Hee Yang, Caroline I Schnegg, Soonyean Hwang, Byungwoo Ryu, Rhoda M Alani
Melanoma is among the most virulent cancers, owing to its propensity to metastasize and its resistance to current therapies. The treatment failure is largely attributed to tumor heterogeneity, particularly subpopulations possessing stem cell-like properties, ie, melanoma stem-like cells (MSLCs). Evidence indicates that the MSLC phenotype is malleable and may be acquired by non-MSLCs through phenotypic switching upon appropriate stimuli, the so-called 'dynamic stemness'. Since the phenotypic characteristics and functional integrity of MSLCs depend on their vascular niche, using a two-dimensional (2D) melanoma-endothelium co-culture model, where the MSLC niche is recapitulated in vitro, we identified Notch3 signaling pathway as a micro-environmental cue governing MSLC phenotypic plasticity via pathway-specific gene expression arrays...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28164774/tauopathies-focus-on-changes-at-the-neurovascular-unit
#17
Alena Michalicova, William A Banks, Jaroslav Legath, Andrej Kovac
In the past, the blood-brain barrier (BBB) had been characterized mainly as a layer of endothelial cells forming the vessel/capillary wall of the brain. More recently, the BBB is considered to be a part of a highly dynamic and interactive system called the neurovascular unit (NVU), consisting of vascular cells, glial cells, and neurons. The list of central nervous system (CNS) pathologies involving BBB dysfunction is rapidly growing. The opening of the BBB and subsequent infiltration of serum components to the brain can lead to host of processes resulting in progressive synaptic and neuronal dysfunction and loss...
February 3, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28149782/six-year-outcomes-in-neovascular-age-related-macular-degeneration-with-ranibizumab
#18
Julie Jacob, Heidi Brié, Anita Leys, Laurent Levecq, Filip Mergaerts, Kris Denhaerynck, Stefaan Vancayzeele, Eline Van Craeyveld, Ivo Abraham, Karen MacDonald
AIM: To evaluate the outcomes of ≥6y ranibizumab therapy in neovascular age-related macular degeneration (AMD). METHODS: HELIX was a retrospective, observational effectiveness study using medical records of patients treated in three clinics in Belgium. Patients had neovascular AMD and were initially treated with intravitreal ranibizumab (0.5 mg) between November 1, 2007 and October 31, 2008, had ≥6y of data available, and were treated on an ongoing, as-needed basis...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28145158/impact-of-dpp-4-inhibition-on-acute-and-chronic-endothelial-function-in-humans-with-type-2-diabetes-on-background-metformin-therapy
#19
Michael E Widlansky, Venkata K Puppala, Tisha M Suboc, Mobin Malik, Amberly Branum, Kara Signorelli, Jingli Wang, Rong Ying, Michael J Tanner, Sudhi Tyagi
: Cell culture and animal work indicate that dipeptidyl peptidase-4 (DPP-4) inhibition may exert cardiovascular benefits through favorable effects on the vascular endothelium. Prior human studies evaluating DPP-4 inhibition have shown conflicting results that may in part be related to heterogeneity of background anti-diabetes therapies. No study has evaluated the acute response of the vasculature to DPP-4 inhibition in humans. We recruited 38 patients with type 2 diabetes on stable background metformin therapy for a randomized, double-blind, placebo-controlled crossover trial of DPP-4 inhibition with sitagliptin (100 mg/day)...
January 1, 2017: Vascular Medicine
https://www.readbyqxmd.com/read/28134810/acidosis-activates-endoplasmic-reticulum-stress-pathways-through-gpr4-in-human-vascular-endothelial-cells
#20
Lixue Dong, Elizabeth A Krewson, Li V Yang
Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the "Warburg effect"), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined...
January 27, 2017: International Journal of Molecular Sciences
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