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https://www.readbyqxmd.com/read/29524527/imidazo-1-2-b-pyridazines-targeting-toxoplasma-gondii-calcium-dependent-protein-kinase-1-decrease-the-parasite-burden-in-mice-with-acute-toxoplasmosis
#1
Espérance Moine, Nathalie Moiré, Isabelle Dimier-Poisson, Kévin Brunet, William Couet, Cyril Colas, Nathalie Van Langendonck, Cécile Enguehard-Gueiffier, Alain Gueiffier, Bruno Héraut, Caroline Denevault-Sabourin, Françoise Debierre-Grockiego
The current therapeutic arsenal for toxoplasmosis is restricted to drugs non-specific to the parasite which cause important side effects. Development of more efficient and specific anti-Toxoplasma compounds is urgently needed. Imidazo[1,2-b]pyridazines designed to inhibit the calcium-dependent protein kinase 1 of Toxoplasma gondii (TgCDPK1) and effective against tachyzoite growth in vitro at submicromolar ranges were modified into hydrochloride salts to be administered in vivo in a mouse model of acute toxoplasmosis...
March 7, 2018: International Journal for Parasitology
https://www.readbyqxmd.com/read/29512755/effects-of-had-b1-on-the-proliferation-of-a549-cisplatin-resistant-lung-cancer-cells
#2
Hwa Jeong Kang, Ji-Hye Park, Hwa-Seung Yoo, Yu Mi Park, Chong-Kwan Cho, In-Cheol Kang
The present study investigated the toxicity of HangAmDan-B1 (HAD-B1) on A549-Cisplatin resistant (A549CR) cells. HAD‑B1 inhibited the growth of A549CR cells in a concentration‑dependent manner; HAD‑B1 was more effective at inhibiting A549CR cell viability compared with vehicle‑treated cells. The reduction in viability may be due to S‑phase cell cycle arrest and the induction of apoptosis in HAD‑B1‑treated cells. Cell cycle protein profile analysis of HAD‑B1‑treated A549CR cells using an InnoPharmaScreen (IPS) ProteoChip‑based antibody microarray chip indicated downregulation of signal transducer and activator of transcription 3...
May 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29496448/the-inhibitory-effect-of-cordycepin-on-the-proliferation-of-cisplatin-resistant-a549-lung-cancer-cells
#3
Seong Hyeok Cho, In-Cheol Kang
The goal of this study is to determine the anti-cancer mechanism of Cordycepin in A549 Cisplatin-Resistance (CR) lung cancer cells. Cordycepin inhibited the viability of A549CR cells in a dose-dependent manner. The cell inhibition was due to induction of apoptosis in the cells treated with Cordycepin by activation of caspase -3, -8 and -9 activities. The cell cycle analysis showed that accumulation of Sub G1 was observed in Cordycepin-treated with A549CR lung cancer cells. Based on the data of expression profile analysis of cell signaling proteins using IPS-FPAA, H-Ras was down-regulated in Cordycepin-treated A549CR cells...
April 6, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29435940/mechanism-and-method-for-generating-tumor-free-ips-cells-using-intronic-microrna-mir-302-induction
#4
Shi-Lung Lin, Shao-Yao Ying
Today's researchers generating induced pluripotent stem cells (iPS cells or iPSCs) usually consider their pluripotency rather than potential tumorigenicity. Oncogenic factors such as c-Myc and Klf4 are frequently used to boost the survival and proliferative rates of iPSCs, creating an inevitable problem of tumorigenicity that hinders the therapeutic usefulness of these iPSCs. To prevent stem cell tumorigenicity, we have examined mechanisms by which the cell cycle genes are regulated in embryonic stem cells (ESCs)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29393405/aurora-a-overexpression-is-linked-to-development-of-aggressive-teratomas-derived-from-human-ips-cells
#5
Seiga Ohmine, Jeffrey L Salisbury, James Ingle, Giuseppe Pettinato, Candace L Haddox, Tufia Haddad, Evanthia Galanis, Yasuhiro Ikeda, Antonino B D'assoro
The discovery of human induced pluripotent stem cells (hiPSCs) is a promising advancement in the field of regenerative and personalized medicine. Expression of SOX2, KLF4, OCT4 and MYC transcription factors induces the nuclear reprogramming of somatic cells into hiPSCs that share striking similarities with human embryonic stem cells (hESCs). However, several studies have demonstrated that hESCs and hiPSCs could lead to teratoma formation in vivo, thus limiting their current clinical applications. Aberrant cell cycle regulation of hESCs is linked to centrosome amplification, which may account, for their enhanced chromosomal instability (CIN), and thus increase their tumorigenicity...
April 2018: Oncology Reports
https://www.readbyqxmd.com/read/29321585/site-specific-randomization-of-the-endogenous-genome-by-a-regulatable-crispr-cas9-piggybac-system-in-human-cells
#6
Kentaro Ishida, Huaigeng Xu, Noriko Sasakawa, Mandy Siu Yu Lung, Julia Alexandra Kudryashev, Peter Gee, Akitsu Hotta
Randomized mutagenesis at an endogenous chromosomal locus is a promising approach for protein engineering, functional assessment of regulatory elements, and modeling genetic variations. In mammalian cells, however, it is challenging to perform site-specific single-nucleotide substitution with single-stranded oligodeoxynucleotide (ssODN) donor templates due to insufficient homologous recombination and the infeasibility of positive selection. Here, we developed a DNA transposon based CRISPR-Cas9 regulated transcription and nuclear shuttling (CRONUS) system that enables the stable transduction of CRISPR-Cas9/sgRNA in broad cell types, but avoids undesired genome cleavage in the absence two chemical inducing molecules...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321255/multisite-emergency-department-inpatient-collaborative-to-reduce-unnecessary-bronchiolitis-care
#7
Grant M Mussman, Michele Lossius, Faiza Wasif, Jeffrey Bennett, Kristin A Shadman, Susan C Walley, Lauren Destino, Elizabeth Nichols, Shawn L Ralston
BACKGROUND AND OBJECTIVES: There is high variation in the care of acute viral bronchiolitis. We sought to promote collaboration between emergency department (ED) and inpatient (IP) units with the goal of reducing unnecessary testing and treatment. METHODS: Multisite collaborative with improvement teams co-led by ED and IP physicians and a 1-year period of active participation. The intervention consisted of a multicomponent change package, regular webinars, and optional coaching...
February 2018: Pediatrics
https://www.readbyqxmd.com/read/29241918/human-amniotic-fluid-stem-cells-have-better-potential-in-early-second-trimester-of-pregnancy-and-can-be-reprogramed-to-ips
#8
S W Steven Shaw, Po-Jen Cheng, Yao-Lung Chang, An-Shine Chao, Tzu-Hao Wang, Shuenn-Dyh Chang, T'sang-T'ang Hsieh, Kuo-Hsuan Chang
OBJECTIVE: To study the difference of amniotic fluid stem cell potential at different gestational age. MATERIALS AND METHODS: Second trimester amniocentesis was performed during 15 to 22nd week of gestational age in a single medical center from 2015 to 2016. Early second trimester amniotic fluid stem cells (E-AFS) and later one (L-AFS) were defined 15-18th week, and 19-22nd week, respectively. Cell characteristics, surface markers and ability to form induced pluripotent stem cells (iPS) were studied...
December 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29159826/pharmacological-and-molecular-approaches-for-the-treatment-of-%C3%AE-hemoglobin-disorders
#9
REVIEW
Neelam Lohani, Nupur Bhargava, Anjana Munshi, Sivaprakash Ramalingam
β-hemoglobin disorders, such as β-thalassemia and sickle cell anemia are among the most prevalent inherited genetic disorders worldwide. These disorders are caused by mutations in the gene encoding hemoglobin-β (HBB), a vital protein found in red blood cells (RBCs) that carries oxygen from lungs to all parts of the human body. As a consequence, there has been an enduring interest in this field in formulating therapeutic strategies for the treatment of these diseases. Currently, there is no cure available for hemoglobin disorders, although, some patients have been treated with bone marrow transplantation, whose scope is limited because of the difficulty in finding a histocompatible donor and also due to transplant-associated clinical complications that can arise during the treatment...
June 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#10
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28967890/long-term-expansion-of-alveolar-stem-cells-derived-from-human-ips-cells-in-organoids
#11
Yuki Yamamoto, Shimpei Gotoh, Yohei Korogi, Masahide Seki, Satoshi Konishi, Satoshi Ikeo, Naoyuki Sone, Tadao Nagasaki, Hisako Matsumoto, Shigeo Muro, Isao Ito, Toyohiro Hirai, Takashi Kohno, Yutaka Suzuki, Michiaki Mishima
The stable expansion of tissue-specific stem cells in vitro has contributed to research on several organs. Alveolar epithelial type II (AT2) cells function as tissue stem cells in the lung, but robust models for studying human AT2 cells are lacking. Here we report a method for the efficient generation and long-term expansion of alveolar organoids (AOs) harboring SFTPC+ alveolar stem cells derived from human induced pluripotent stem cells (hiPSCs). hiPSC-derived SFTPC+ cells self-renewed, with transcriptomes and morphology consistent with those of AT2 cells, and were able to differentiate into alveolar epithelial type I (AT1)-like cells...
November 2017: Nature Methods
https://www.readbyqxmd.com/read/28815470/alterations-in-scai-expression-during-cell-plasticity-fibrosis-and-cancer
#12
Ákos Gasparics, Gábor Kökény, Attila Fintha, Rita Bencs, Miklós M Mózes, Emese Irma Ágoston, Anna Buday, Zoltán Ivics, Péter Hamar, Balázs Győrffy, László Rosivall, Attila Sebe
Suppressor of cancer cell invasion (SCAI) has been originally characterized as a tumor suppressor inhibiting metastasis in different human cancer cells, and it has been suggested that SCAI expression declines in tumors. The expression patterns and role of SCAI during physiological and pathophysiological processes is still poorly understood. Earlier we demonstrated that SCAI is regulating the epithelial-mesenchymal transition of proximal tubular epithelial cells, it is downregulated during renal fibrosis and it is overexpressed in Wilms' tumors...
August 16, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28782268/reprogramming-antagonizes-the-oncogenicity-of-hoxa13-long-noncoding-rna-hottip-axis-in-gastric-cancer-cells
#13
Deng-Chyang Wu, Sophie S W Wang, Chung-Jung Liu, Kenly Wuputra, Kohsuke Kato, Yen-Liang Lee, Ying-Chu Lin, Ming-Ho Tsai, Chia-Chen Ku, Wen-Hsin Lin, Shin-Wei Wang, Shotaro Kishikawa, Michiya Noguchi, Chu-Chieh Wu, Yi-Ting Chen, Chee-Yin Chai, Chen-Lung Steve Lin, Kung-Kai Kuo, Ya-Han Yang, Hiroyuki Miyoshi, Yukio Nakamura, Shigeo Saito, Kyosuke Nagata, Chang-Shen Lin, Kazunari K Yokoyama
Reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP7 promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase, WD repeat-containing protein 5, and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells...
August 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28673995/inhibition-of-acute-lethal-pulmonary-inflammation-by-the-ido-ahr-pathway
#14
Soung-Min Lee, Ha Young Park, Young-Sill Suh, Eun Hye Yoon, Juyang Kim, Won Hee Jang, Won-Sik Lee, Sae-Gwang Park, Il-Whan Choi, Inhak Choi, Sun-Woo Kang, Hwayoung Yun, Takanori Teshima, Byungsuk Kwon, Su-Kil Seo
The lung is a prototypic organ that was evolved to reduce immunopathology during the immune response to potentially hazardous endogenous and exogenous antigens. In this study, we show that donor CD4(+) T cells transiently induced expression of indoleamine 2,3-dioxygenase (IDO) in lung parenchyma in an IFN-γ-dependent manner early after allogeneic hematopoietic stem cell transplantation (HSCT). Abrogation of host IDO expression by deletion of the IDO gene or the IFN-γ gene in donor T cells or by FK506 treatment resulted in acute lethal pulmonary inflammation known as idiopathic pneumonia syndrome (IPS)...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28649446/phenotypic-profiling-of-cftr-modulators-in-patient-derived-respiratory-epithelia
#15
Saumel Ahmadi, Zoltan Bozoky, Michelle Di Paola, Sunny Xia, Canhui Li, Amy P Wong, Leigh Wellhauser, Steven V Molinski, Wan Ip, Hong Ouyang, Julie Avolio, Julie D Forman-Kay, Felix Ratjen, Jeremy A Hirota, Johanna Rommens, Janet Rossant, Tanja Gonska, Theo J Moraes, Christine E Bear
Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis, a disease caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Heterogeneity in CFTR genotype-phenotype relationships in affected individuals plus the escalation of drug discovery targeting specific mutations highlights the need to develop robust in vitro platforms with which to stratify therapeutic options using relevant tissue. Toward this goal, we adapted a fluorescence plate reader assay of apical CFTR-mediated chloride conductance to enable profiling of a panel of modulators on primary nasal epithelial cultures derived from patients bearing different CFTR mutations...
April 14, 2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28372287/organ-reconstruction-dream-or-reality-for%C3%A2-the%C3%A2-future
#16
REVIEW
J-F Stoltz, L Zhang, J S Ye, N De Isla
The relevance of research on reconstructed organs is justified by the lack of organs available for transplant and the growing needs for the ageing population. The development of a reconstructed organ involves two parallel complementary steps: de-cellularization of the organ with the need to maintain the structural integrity of the extracellular matrix and vascular network and re-cellularization of the scaffold with stem cells or resident cells.Whole organ engineering for liver, heart, lung or kidneys, is particularly difficult because of the structural complexity of organs and heterogeneity of cells...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28366292/integrating-lung-physiology-immunology-and-tuberculosis
#17
REVIEW
Jordi B Torrelles, Larry S Schlesinger
Lungs are directly exposed to the air, have enormous surface area, and enable gas exchange in air-breathing animals. They are constantly 'attacked' by microbes from both outside and inside and thus possess a unique, highly regulated local immune defense system which efficiently allows for microbial clearance while minimizing damaging inflammatory responses. As a prototypic host-adapted airborne pathogen, Mycobacterium tuberculosis traverses the lung and has several 'interaction points' (IPs) which it must overcome to cause infection...
August 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28332899/in-vitro-tests-for-aerosol-deposition-v-using-realistic-testing-to-estimate-variations-in-aerosol-properties-at-the-trachea
#18
Xiangyin Wei, Michael Hindle, Renishkumar R Delvadia, Peter R Byron
BACKGROUND: The dose and aerodynamic particle size distribution (APSD) of drug aerosols' exiting models of the mouth and throat (MT) during a realistic inhalation profile (IP) may be estimated in vitro and designated Total Lung Dose, TLDin vitro, and APSDTLDin vitro, respectively. These aerosol characteristics likely define the drug's regional distribution in the lung. METHODS: A general method was evaluated to enable the simultaneous determination of TLDin vitro and APSDTLDin vitro for budesonide aerosols' exiting small, medium and large VCU-MT models...
October 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28326803/when-is-an-alveolar-type-2-cell-an-alveolar-type-2-cell-a-conundrum-for-lung-stem-cell-biology-and-regenerative-medicine
#19
REVIEW
Michael F Beers, Yuben Moodley
Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors...
July 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28242132/abducens-nerve-palsy-due-to-inferior-petrosal-sinus-thrombosis
#20
Shivam Om Mittal, Junaid Siddiqui, Bashar Katirji
Isolated unilateral abducens nerve palsy is usually due to ischemia, trauma or neoplasm. Dorello's canal is the space between the petrous apex and superolateral portion of the clivus, bound superiorly by Gruber's ligament. The abducens nerve travels with inferior petrosal sinus (IPS) though the Dorello's canal before entering the cavernous sinus. A 31-year-old man presented with neck pain, and binocular horizontal diplopia, worse looking towards left and at distance. He had a history of intravenous drug abuse but no history of hypertension or diabetes...
June 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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