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https://www.readbyqxmd.com/read/29901076/lipid-raft%C3%A2-associated-%C3%AE-%C3%A2-adducin-participates-in-neutrophil-migration
#1
Chen Yang, Zhefeng Sui, Tingshuang Xu, Wenai Liu, Xiaoguang Wang, Xianlu Zeng
Previous studies have demonstrated that lipid rafts and β‑adducin serve an important role in leukocyte rolling. In the present study the migratory ability and behavior of neutrophils was demonstrated to rely on the integrity of the lipid raft structure. β‑adducin was demonstrated to have a critical role in neutrophil migration. Knockdown of β‑adducin attenuated the migratory ability of dHL‑60 cells and the distribution of β‑adducin in lipid raft structures was changed by N‑formylmethionyl‑leucyl‑phenyl‑alanine treatment...
May 31, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29899382/constitutive-ip-3-signaling-underlies-the-sensitivity-of-b-cell-cancers-to-the-bcl-2-ip-3-receptor-disruptor-bird-2
#2
Mart Bittremieux, Rita M La Rovere, Haidar Akl, Claudio Martines, Kirsten Welkenhuyzen, Kathia Dubron, Myriam Baes, Ann Janssens, Peter Vandenberghe, Luca Laurenti, Katja Rietdorf, Giampaolo Morciano, Paolo Pinton, Katsuhiko Mikoshiba, Martin D Bootman, Dimitar G Efremov, Humbert De Smedt, Jan B Parys, Geert Bultynck
Anti-apoptotic Bcl-2 proteins are upregulated in different cancers, including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), enabling survival by inhibiting pro-apoptotic Bcl-2-family members and inositol 1,4,5-trisphosphate (IP3 ) receptor (IP3 R)-mediated Ca2+ -signaling. A peptide tool (Bcl-2/IP3 R Disruptor-2; BIRD-2) was developed to abrogate the interaction of Bcl-2 with IP3 Rs by targeting Bcl-2's BH4 domain. BIRD-2 triggers cell death in primary CLL cells and in DLBCL cell lines...
June 13, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29876927/carious-lesion-severity-and-demarcated-hypomineralised-lesions-of-tooth-enamel-in-schoolchildren-from-melbourne-australia
#3
K Gambetta-Tessini, R Mariño, A Ghanim, H Calache, D J Manton
BACKGROUND: Developmental hypomineralised lesions of enamel (DHL) may represent a significant caries-risk factor. The present study's aim is to determine the association between carious lesion severity and DHL in 6 to 12-year-old schoolchildren from Melbourne, Australia. METHODS: The sample was derived from randomly selected schools in inner Melbourne. A full dental examination was performed at the school. Socio-demographic data, caries experience (DMFT/dmft/ICDAS II) and the consequences of untreated carious lesions (PUFA/pufa) were measured...
June 7, 2018: Australian Dental Journal
https://www.readbyqxmd.com/read/29786748/protective-effects-of-dehydrocostuslactone-on-rat-hippocampal-slice-injury-induced-by-oxygen%C3%A2-glucose-deprivation-reoxygenation
#4
Qipeng Zhao, Ailing Chen, Xiaobo Wang, Zhuanzhuan Zhang, Yunsheng Zhao, Yu Huang, Shuanglai Ren, Yafei Zhu
The present study aimed to investigate the protective effects of dehydrocostuslactone (DHL) against rat hippocampal slice injury caused by oxygen‑glucose deprivation/reoxygenation (OGD/R). Rat hippocampal slice injury was induced by OGD/R in vitro, and the degree of injury was evaluated through a lactate dehydrogenase (LDH) assay and 2,3,5‑triphenyltetrazolium chloride (TTC) staining. The protein expression levels of B‑cell lymphoma-2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), cytochrome c (cyt‑c), apoptotic protease activating factor 1 (apaf‑1), caspase‑9, caspase‑7, caspase‑3, sequestosome 1 (SQSTM1) and microtubule‑associated protein 1 light chain 3 (LC3) were analyzed through western blot analysis...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29774652/nonscarring-diffuse-hair-loss-in-women-a-clinico-etiological-study-from-tertiary-care-center-in-north-west-india
#5
Kavita Poonia, Gurvinder Pal Thami, Mala Bhalla, Shivani Jaiswal, Jasleen Sandhu
BACKGROUND: Diffuse hair loss (DHL) is a common problem in adult women and has a major impact on quality of life. Ascertaining the etiological diagnosis is a challenging task in such patients. Satisfactory treatment can only be instituted after ascertaining the cause of hair loss. OBJECTIVE: To study the clinico-epidemiological profile of nonscarring DHL in females and to ascertain its underlying etiological factors. STUDY DESIGN: Of a total of 110 females, who presented with nonscarring DHL to the outpatient dermatology department, 100 qualified for inclusion in the study...
May 17, 2018: Journal of Cosmetic Dermatology
https://www.readbyqxmd.com/read/29731969/indolent-lymphoma-with-composite-histology-and-simultaneous-transformation-at-initial-diagnosis-exhibit-clinical-features-similar-to-de-novo-diffuse-large-b-cell-lymphoma
#6
Hanno Witte, Harald Biersack, Svenja Kopelke, Dirk Rades, Hartmut Merz, Veronica Bernard, Hendrik Lehnert, Niklas Gebauer
While various studies characterized clinical and prognostic properties of de novo diffuse large B-Cell lymphoma (DLBCL) and transformed indolent lymphomas, the clinicopathological features of indolent lymphoma and simultaneous secondary transformation upon initial diagnosis (ssDLBCL) are insufficiently established. Between 2010 and 2017, 247 consecutive patients admitted to our institution and treated for DLBCL were investigated for composite histology of ssDLBCL-type. Upon systematical histopathological evaluation composite histology was identified in 22/247 cases (8...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29722657/patterns-of-failure-in-patients-with-double-hit-or-double-expressor-lymphomas-implications-for-radiation-therapy
#7
Vasu Tumati, Lakshya Trivedi, Hsiao-Ching Li, Prapti Patel, Pier P Scaglioni, Madhuri Vusirikala, Navid Sadeghi, Syed Rizvi, Weina Chen, Jason Wachsmann, Robert Collins, Neil B Desai
PURPOSE: Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy. Optimal therapy is not clear, and little information exists on the contribution of consolidative radiation therapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiation therapy in unselected diffuse large B-cell lymphoma (DLBCL)...
April 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29681711/diagnostic-hysterolaparoscopy-for-evaluation-of-infertility-our-experience-in-a-tertiary-care-hospital
#8
Sairem Mangolnganbi Chanu, Gouri Sankar Rudra Pal, Subrat Panda, A S Santa Singh
Objective: The objective of this study is to analyze the role of diagnostic hysterolaparoscopy (DHL) for evaluation of infertility in a tertiary care hospital. Materials and Methods: This retrospective study was conducted from July 2014 to June 2016. Results: Out of 151 patients, 58.28% and 41.72% had primary and secondary infertility, respectively. In primary infertility group 37.5% and in secondary infertility group 49.2% had abnormal findings...
January 2018: Journal of Human Reproductive Sciences
https://www.readbyqxmd.com/read/29649047/preliminary-outcomes-report-for-co2-laser-assisted-electric-acoustic-cochlear-implantation
#9
Shawn M Stevens, Andrew Redmann, Kayla Whitaker, Alyson Ruotanen, Lisa Houston, Theresa Hammer, Ravi N Samy
OBJECTIVE: Report on the safety/efficacy of a novel, carbon dioxide (CO2) laser-assisted protocol for hearing-preservation cochlear implantation (HPCI) and electric-acoustic stimulation (EAS). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Adult patients meeting established criteria for HPCI and EAS. INTERVENTION: Therapeutic/rehabilitative. A standardized protocol used CO2 laser to achieve meticulous hemostasis and perform cochleostomy was evaluated...
June 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29629947/identification-of-double-hit-lymphomas-using-updated-who-criteria-insights-from-routine-myc-immunohistochemistry-in-272-consecutive-cases-of-aggressive-b-cell-lymphomas
#10
Hany Sakr, James R Cook
Aggressive lymphomas with MYC and BCL2 and/or BCL6 translocations ("double hit" lymphomas, DHL) represent a distinct diagnostic category in the updated World Health Organization (WHO) classification. The diagnostic yield of MYC immunohistochemistry (IHC) for the identification of DHL is currently uncertain. MYC IHC was performed in 272 consecutive cases of aggressive B-cell lymphoma, and results correlated with fluorescence in situ hybridization (FISH) for MYC translocations. Among 156 patients with IHC and FISH data, MYC IHC identified MYC translocations with 89% sensitivity, 38% specificity, 92% negative predictive value, and 29% positive predictive value...
April 7, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29627725/proteolysis-targeting-chimeras-protacs-of-anaplastic-lymphoma-kinase-alk
#11
Chengwei Zhang, Xiao-Ran Han, Xiaobao Yang, Biao Jiang, Jing Liu, Yue Xiong, Jian Jin
Anaplastic lymphoma kinase (ALK) activation has been associated with many types of human cancer. Significant efforts have been devoted to the development of ALK inhibitors to antagonize the kinase activity of ALK. Four ALK inhibitors have been approved by the FDA to date for treating patients with ALK-positive non-small cell lung cancers (NSCLC). However, drug resistance has been observed in the majority of patients treated with these inhibitors. New therapeutic strategies (e.g., compounds with novel mechanisms of action) are needed to overcome the drug resistance issue...
May 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29601991/discovery-of-novel-quinazolinone-derivatives-as-high-potent-and-selective-pi3k%C3%AE-and-pi3k%C3%AE-%C3%AE-inhibitors
#12
Chen-Chen Ma, Cheng-Mei Zhang, Long-Qian Tang, Zhao-Peng Liu
PI3Kδ and PI3Kγ regulate immune cell signaling. Selective PI3Kδ or PI3Kγ inhibitors and dual PI3Kδ/γ inhibitors have the potential for the treatment of immune cell-mediated diseases and hematological malignancies. Based on the quinazolinone pharmacophore, we used a pyrazolo[3,4-d]pyrimidin-4-amine portion as the hinge region binding moiety, an aromatic or a heteroaromatic substituent at the 3-position of the pyrazolo[3,4-d]pyrimidine core as the affinity element, and designed novel 2-tolyl and 2,6-dimethylphenyl quinazolinone derivatives as potential PI3Kδ inhibitors...
May 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29593718/secretion-of-the-phosphorylated-form-of-s100a9-from-neutrophils-is-essential-for-the-proinflammatory-functions-of-extracellular-s100a8-a9
#13
Véronique Schenten, Sébastien Plançon, Nicolas Jung, Justine Hann, Jean-Luc Bueb, Sabrina Bréchard, Eric J Tschirhart, Fabrice Tolle
S100A8 and S100A9 are members of the S100 family of cytoplasmic EF-hand Ca2+ -binding proteins and are abundantly expressed in the cytosol of neutrophils. In addition to their intracellular roles, S100A8/A9 can be secreted in the extracellular environment and are considered as alarmins able to amplify the inflammatory response. The intracellular activity of S100A8/A9 was shown to be regulated by S100A9 phosphorylation, but the importance of this phosphorylation on the extracellular activity of S100A8/A9 has not yet been extensively studied...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29536777/introduction-of-pyrrolidineoxy-or-piperidineamino-group-at-the-4-position-of-quinazoline-leading-to-novel-quinazoline-based-phosphoinositide-3-kinase-delta-pi3k%C3%AE-inhibitors
#14
Minhang Xin, Weiming Duan, Yifan Feng, Yuan-Yuan Hei, Hao Zhang, Ying Shen, Hong-Yi Zhao, Shuai Mao, San-Qi Zhang
Phosphoinositide 3-kinase Delta (PI3Kδ) plays a key role in B-cell signal transduction and inhibition of PI3Kδ was confirmed to have clinical benefit in certain types of activation of B-cell malignancies. Herein, we reported a novel series of 4-pyrrolidineoxy or 4-piperidineamino substituted quinazolines, showing potent PI3Kδ inhibitory activities. Among these compounds, 12d, 14b and 14c demonstrated higher potency against PI3Kδ with the half maximal inhibitory concentration (IC50 ) values of 4.5, 3.0, and 3...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29534936/novel-6-aryl-substituted-4-pyrrolidineaminoquinazoline-derivatives-as-potent-phosphoinositide-3-kinase-delta-pi3k%C3%AE-inhibitors
#15
Minhang Xin, Weiming Duan, Yifan Feng, Yuan-Yuan Hei, Hao Zhang, Ying Shen, Hong-Yi Zhao, Shuai Mao, San-Qi Zhang
In this study, a novel series of 6-aryl substituted 4-pyrrolidineaminoquinazoline derivatives were designed and evaluated as potent PI3Kδ inhibitors. The preliminary SAR was established, and compounds 12d, 20a and 20c displayed leading potent PI3Kδ inhibition, with IC50 values of 4.5, 2.7 and 3.1 nM, respectively, that were comparable to idelalisib (IC50  = 2.7 nM). Moreover, these three compounds showed favorable PI3Kδ isoform selectivity over PI3Kα, PI3Kβ, and PI3Kγ, and showed distinct anti-proliferation profiles against four human B cell lines of Ramos, Raji, RPMI-8226 and SU-DHL-6...
May 1, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29510342/uric-acid-disrupts-hypochlorous-acid-production-and-the-bactericidal-activity-of-hl-60-cells
#16
Larissa A C Carvalho, João P P B Lopes, Gilberto H Kaihami, Railmara P Silva, Alexandre Bruni-Cardoso, Regina L Baldini, Flavia C Meotti
Uric acid is the end product of purine metabolism in humans and is an alternative physiological substrate for myeloperoxidase. Oxidation of uric acid by this enzyme generates uric acid free radical and urate hydroperoxide, a strong oxidant and potentially bactericide agent. In this study, we investigated whether the oxidation of uric acid and production of urate hydroperoxide would affect the killing activity of HL-60 cells differentiated into neutrophil-like cells (dHL-60) against a highly virulent strain (PA14) of the opportunistic pathogen Pseudomonas aeruginosa...
June 2018: Redox Biology
https://www.readbyqxmd.com/read/29500147/a-retrospective-study-of-double-hit-lymphomas-in-elderly-patients-aged-70-years-overall-outcomes
#17
Christie Hancock, Phillip Knouse, Imad Almanaseer, Jacob Bitran
BACKGROUND: Double-hit lymphomas (DHLs) are high-grade diffuse large B-cell lymphomas with concurrent translocations involving myc and bcl-2 and/or bcl-6. A patient with DHL often has advanced disease at presentation and typically responds poorly to standard therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). More intensive treatment regimens have been studied; however, few data are available on the outcomes in elderly patients (aged > 70 years) treated with these therapies...
April 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29445868/induction-of-systemic-resistance-in-tomato-against-botrytis-cinerea-by-n-decanoyl-homoserine-lactone-via-jasmonic-acid-signaling
#18
Zhangjian Hu, Shujun Shao, Chenfei Zheng, Zenghui Sun, Junying Shi, Jingquan Yu, Zhenyu Qi, Kai Shi
N-decanoyl-homoserine lactone activates plant systemic resistance against Botrytis cinerea in tomato plants, which is largely dependent on jasmonic acid biosynthesis and signal transduction pathways. Rhizosphere bacteria secrete N-acylated-homoserine lactones (AHLs), a type of specialized quorum-sensing signal molecule, to coordinate their population density during communication with their eukaryotic hosts. AHLs behave as low molecular weight ligands that are sensed by plants and promote the host's resistance against foliar pathogens...
May 2018: Planta
https://www.readbyqxmd.com/read/29427012/-blood-pressure-targets-the-lower-the-better-does-not-suit-all
#19
REVIEW
U Hoffmann
BACKGROUND: The systolic blood pressure intervention trial (SPRINT) published in 2015 has opened up new discussions on whether a lower blood pressure target as recommended by the current guidelines would be better for some patient groups. OBJECTIVES: To review patient groups in which lower blood pressure targets would not be better. MATERIALS AND METHODS: The results of SPRINT, its post-hoc and subgroup analyses, other studies and newer studies, as well as metaanalyses on the topic of blood pressure targets are reviewed and discussed...
April 2018: Der Internist
https://www.readbyqxmd.com/read/29419530/challenges-and-opportunities-for-high-grade-b-cell-lymphoma-with-myc-and-bcl2-and-or-bcl6-rearrangement-double-hit-lymphoma
#20
Dongfeng Zeng, Aakash Desai, Fangfang Yan, Tiejun Gong, Haige Ye, Makhdum Ahmed, Krystle Nomie, Jorge Romaguera, Richard Champlin, Shaoying Li, Michael Wang
The most common subtype of non-Hodgkin lymphoma, diffuse large B-cell lymphoma, is cured in approximately two thirds of patients after initial therapy. The remaining one-third of patients who suffer relapse or become refractory have very poor survival outcomes despite salvage chemotherapy with or without stem cell transplantation. A considerable proportion of relapsed or refractory large B cells belong to the WHO subtype known as high-grade B-cell lymphoma with rearrangement of MYC and BCL2 and/or BCL6, also known as double-hit lymphoma (DHL)...
February 6, 2018: American Journal of Clinical Oncology
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