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https://www.readbyqxmd.com/read/29156206/cytokine-release-syndrome-who-is-at-risk-and-how-to-treat
#1
REVIEW
Noelle Frey
T-cell engaging therapies such as blinatumomab and anti-CD19 chimeric antigen receptor (CAR) T cells have revolutionized our approach to patients with relapsed and refractory acute lymphoblastic leukemia (ALL). However, the immune activation responsible for high remission rates is also responsible for the unique treatment-related toxicity of cytokine release syndrome (CRS). The clinical signs of CRS include fever, hemodynamic instability, and capillary leak, which correlate with T-cell activation and elevated cytokine levels...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29154907/an-integrated-mathematical-epithelial-cell-model-for-airway-surface-liquid-regulation-by-mechanical-forces
#2
Dan Wu, Richard C Boucher, Brian Button, Timothy Elston, Ching-Long Lin
A robust method based on reverse engineering was utilized to construct the ion-channel conductance functions for airway epithelial sodium channels (ENaC), the cystic fibrosis transmembrane conductance regulator (CFTR), and calcium-activated chloride channels (CaCC). The ion-channel conductance models for both normal (NL) and cystic fibrosis (CF) airway epithelia were developed and then coupled to an adenosine triphosphate (ATP) metabolism model and a fluid transport model (collectively called the integrated cell model) to investigate airway surface liquid (ASL) volume regulation and hence mucus concentration, by mechanical forces in NL and CF human airways...
November 15, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29153608/cofilin-signaling-in-hemin-induced-microglial-activation-and-inflammation
#3
Muhammad Shahdaat Bin Sayeed, Qasim Alhadidi, Zahoor A Shah
Intracerebral hemorrhage (ICH) is the most severe form of stroke and is further exacerbated by the secondary injury involving inflammatory response due to the activation of microglia. This secondary injury is partly due to the toxic effects of hemin, an endogenous breakdown product of hemoglobin. Cofilin, an actin depolymerizing factor, controls actin dynamics and has been previously shown to be involved in mediating neuronal cell death in ischemic conditions and during bacterial lipopolysaccharide induced microglial activation...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29150328/randomized-phase-2-therapeutic-equivalence-study-of-abiraterone-acetate-fine-particle-formulation-vs-originator-abiraterone-acetate-in-patients-with-metastatic-castration-resistant-prostate-cancer-the-staar-study
#4
Cy A Stein, Richard Levin, Robert Given, Celestia S Higano, Paul Nemeth, Bill Bosch, Jillian Chapas-Reed, Robert Dreicer
BACKGROUND: This multicenter, randomized, open-label, active-controlled study evaluated therapeutic equivalence, steady-state pharmacokinetics, and safety of a novel abiraterone acetate fine particle formulation (AAFP) 500mg plus methylprednisolone vs. the originator AA (OAA) 1000mg plus prednisone in men with metastatic castrate-resistant prostate cancer (mCRPC). The primary endpoint was a comparison of average of serum testosterone levels on treatment days 9 and 10 between groups. METHODS: Men with progressive mCRPC, receiving gonadotropin-releasing hormone agonist or antagonist therapy, and with a serum testosterone level of <50ng/dl were randomized 1:1 to either AAFP 500mg daily plus 4mg methylprednisolone orally twice daily (BID), or OAA 1000mg daily plus 5mg prednisone BID for 84 days...
November 14, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29149414/role-of-tctp-for-cellular-differentiation-and-cancer-therapy
#5
Ean-Jeong Seo, Nicolas Fischer, Thomas Efferth
The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29148428/-sup-135-sup-la-as-an-auger-electron-emitter-for-targeted-internal-radiotherapy
#6
Jesper Fonslet, Boon Quan Lee, Thuy A Tran, Mattia Siragusa, Mikael Jensen, Tibor Kibedi, Andrew E Stuchbery, Gregory W Severin
<b>Introduction:</b> <sup>135</sup>La has favorable nuclear and chemical properties for Auger-based targeted internal radiotherapy. Here we present detailed investigations of the production, emissions, imaging characteristics, and dosimetry related to <sup>135</sup>La therapy. <b>Methods and Results:</b> <sup>135</sup>La was produced by 16.5 MeV proton irradiation of metallic <sup>nat</sup>Ba on a medical cyclotron, and was isolated and purified by trap-and-release on weak cation-exchange resin...
November 17, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29146540/temperature-sensitive-copolymer-coated-fluorescent-mesoporous-silica-nanoparticles-as-a-reactive-oxygen-species-activated-drug-delivery-system
#7
Feng Yu, Huijing Wu, Yao Tang, Yufang Xu, Xuhong Qian, Weiping Zhu
In this study, a temperature and ROS-responsive drug delivery system ROSP@MSN based on mesoporous silica nanoparticles has been designed and synthesized by taking advantage of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate modified polymers (ROSP) as "nano-valve", which can respond selectively to cancer exclusive microenvironment and implement targeted drug release. Due to the superior temperature-sensitive properties of ROSP, ROSP@MSN could achieve cargo loading in cold water, and subsequently close the pore by raising temperature to obtain ROSP@MSN@DOX...
November 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29142837/preoperative-management-in-patients-with-graves-disease
#8
REVIEW
Eliana Piantanida
Graves' disease is the most frequent cause of hyperthyroidism in iodine-sufficient geographical areas and is characterized by the presence in patients' serum of autoantibodies directed against the thyrotropin receptor (TRAb) that cause overproduction and release of thyroid hormones. Clinical presentation results from both hyperthyroidism and underlying autoimmunity. The diagnosis is based on characteristic clinical features and biochemical abnormalities. If serum thyrotropin (TSH) is low, serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations should be measured to distinguish between subclinical (with normal circulating thyroid hormones) and overt hyperthyroidism (with increased circulating thyroid hormones)...
October 2017: Gland Surgery
https://www.readbyqxmd.com/read/29142313/effects-of-exosome-on-the-activation-of-cd4-t-cells-in-rhesus-macaques-a-potential-application-for-hiv-latency-reactivation
#9
Xiaowu Hong, Blake Schouest, Huanbin Xu
Exosomes are small extracellular vesicles (EVs), released by a wide variety of cell types, carry donor origin-proteins, cytokines, and nucleic acids, transport these cargos to adjacent or distant specific recipient cells, and thereby regulate gene expression and activation of target cells. In this study, we isolated and identified exosomes in rhesus macaques, and investigated their effects on cell tropism and activation, especially their potential to reactivate HIV latency. The results indicated that plasma-derived exosomes preferentially fuse to TCR-activated T cells and autologous parent cells...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141866/prostate-specific-membrane-antigen-cleavage-of-vitamin-b9-stimulates-oncogenic-signaling-through-metabotropic-glutamate-receptors
#10
Charalambos Kaittanis, Chrysafis Andreou, Haley Hieronymus, Ninghui Mao, Catherine A Foss, Matthias Eiber, Gregor Weirich, Palak Panchal, Anuradha Gopalan, Juan Zurita, Samuel Achilefu, Gabriela Chiosis, Vladimir Ponomarev, Markus Schwaiger, Brett S Carver, Martin G Pomper, Jan Grimm
Prostate-specific membrane antigen (PSMA) or folate hydrolase 1 (FOLH1) is highly expressed on prostate cancer. Its expression correlates inversely with survival and increases with tumor grade. However, the biological role of PSMA has not been explored, and its role in prostate cancer remained elusive. Filling this gap, we demonstrate that in prostate cancer, PSMA initiates signaling upstream of PI3K through G protein-coupled receptors, specifically via the metabotropic glutamate receptor (mGluR). PSMA's carboxypeptidase activity releases glutamate from vitamin B9 and other glutamated substrates, which activate mGluR I...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141010/multiple-effects-of-toxins-isolated-from-crotalus-durissus-terrificus-on-the-hepatitis-c-virus-life-cycle
#11
Jacqueline Farinha Shimizu, Carina Machado Pereira, Cintia Bittar, Mariana Nogueira Batista, Guilherme Rodrigues Fernandes Campos, Suely da Silva, Adélia Cristina Oliveira Cintra, Carsten Zothner, Mark Harris, Suely Vilela Sampaio, Victor Hugo Aquino, Paula Rahal, Ana Carolina Gomes Jardim
Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle...
2017: PloS One
https://www.readbyqxmd.com/read/29137551/environmental-manipulations-as-an-effective-alternative-treatment-to-reduce-endometriosis-progression
#12
Annelyn Torres-Reverón, Leslie L Rivera, Idhaliz Flores, Caroline B Appleyard
Treatments for endometriosis include pharmacological or surgical procedures that produce significant side effects. We aimed to determine how environmental enrichment (EE) could impact the progression of endometriosis using the autotransplantation rat model. Female rats were exposed to EE (endo-EE: toys and nesting materials, 4 rats per cage, larger area enclosure) or no enrichment (endo-NE: 2 rats per cage) starting on postnatal day 21. After 8 weeks, sham surgery or surgical endometriosis was induced by suturing uterine horn tissue next to the intestinal mesentery, then allowed to progress for 60 days during which EE or NE continued...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29137240/mutational-re-modeling-of-di-aspartyl-intramembrane-proteases-uncoupling-physiologically-relevant-activities-from-those-associated-with-alzheimer-s-disease
#13
Anastasia P Grigorenko, Youri K Moliaka, Olga V Plotnikova, Alexander Smirnov, Vera A Nikishina, Andrey Y Goltsov, Fedor Gusev, Tatiana V Andreeva, Omar Nelson, Ilya Bezprozvanny, Evgeny I Rogaev
The intramembrane proteolytic activities of presenilins (PSEN1/PS1 and PSEN2/PS2) underlie production of β-amyloid, the key process in Alzheimer's disease (AD). Dysregulation of presenilin-mediated signaling is linked to cancers. Inhibition of the γ-cleavage activities of PSENs that produce Aβ, but not the ε-like cleavage activity that release physiologically essential transcription activators, is a potential approach for the development of rational therapies for AD. In order to identify whether different activities of PSEN1 can be dissociated, we designed multiple mutations in the evolutionary conserved sites of PSEN1...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136767/the-exposure-effect-toxicity-correlation-of-docetaxel-and-magnesium-isoglycyrrhizinate-in-non-small-cell-lung-tumor-bearing-mice
#14
Peijin Li, Suning Li, Hongmei Gu, Qianfeng Lu, Wenjiao Jiang, Xue Pei, Yilin Sun, Hongjiang Xu, Guangji Wang, Kun Hao
To take full advantage of combination therapy of Docetaxel (DTX) and Magnesium isoglycyrrhizinate (MGIG), the pharmacokinetic- pharmacodynamic- toxicodynamics (PK-PD-TD) interaction of DTX and MGIG in non-small cell lung tumor-bearing mice was investigated in the present study. A model, an integrated semi-mechanistic PK-PD-TD, was established for elucidating the exposure-effect-toxicity relationship between DTX and MGIG. A tumor growth and a transit compartmental system were applied to imitate the growth and death of tumor cell...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29135655/neutrophil-activation-and-enhanced-release-of-granule-products-in-hiv-tb-immune-reconstitution-inflammatory-syndrome
#15
Justine K Nakiwala, Naomi F Walker, Collin R Diedrich, William Worodria, Graeme Meintjes, Robert J Wilkinson, Harriet Mayanja-Kizza, Robert Colebunders, Luc Kestens, Katalin A Wilkinson, David M Lowe
BACKGROUND: Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) remains incompletely understood. Neutrophils are implicated in tuberculosis pathology but detailed investigations in TB-IRIS are lacking. We sought to further explore the biology of TB-IRIS and in particular the role of neutrophils. SETTING: Two observational, prospective cohort studies in HIV/TB co-infected patients starting antiretroviral therapy, one to analyze gene expression and subsequently one to explore neutrophil biology...
November 6, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29135573/evidence-of-inflammasome-activation-and-formation-of-monocyte-derived-apoptosis-associated-speck-like-protein-containing-a-caspase-recruitment-domain-specks-in-hiv-1-positive-patients
#16
Fareed Ahmad, Neha Mishra, Gerrit Ahrenstorf, Bernardo S Franklin, Eicke Latz, Reinhold E Schmidt, Lukas Bossaller
OBJECTIVE: The formation of large intracellular protein aggregates of the inflammasome adaptor apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) (PYCARD) is a hallmark of inflammasome activation. ASC speck-forming cells release the highly proinflammatory cytokine IL-1β in addition to ASC specks into the extracellular space during pyroptotic cell death. There ASC specks can propagate inflammation to other nonactivated cells or tissues. HIV-1 retroviral infection triggers inflammasome activation of abortively infected CD4 T cells in secondary lymphatic tissues...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29134588/encapsulation-strategies-of-bacteriophage-felix-o1-for-oral-therapeutic-application
#17
Golam S Islam, Qi Wang, Parviz M Sabour
Due to emerging antibiotic-resistant strains among the pathogens, a variety of strategies, including therapeutic application of bacteriophages, have been suggested as a possible alternative to antibiotics in food animal production. As pathogen-specific biocontrol agents, bacteriophages are being studied intensively. Primarily their applications in the food industry and animal production have been recognized in the USA and Europe, for pathogens including Salmonella, Campylobacter, Escherichia coli, and Listeria...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29133856/therapeutic-targeting-of-extracellular-dna-improves-the-outcome-of-intestinal-ischemic-reperfusion-injury-in-neonatal-rats
#18
Michael Boettcher, Georg Eschenburg, Stefan Mietzsch, Miguel Jiménez-Alcázar, Michaela Klinke, Deirdre Vincent, Bastian Tiemann, Robert Bergholz, Konrad Reinshagen, Tobias A Fuchs
Thrombosis and inflammation cooperate in the development of intestinal infarction. Recent studies suggest that extracellular DNA released by damaged cells or neutrophils in form of extracellular traps (NETs) contributes to organ damage in experimental models of ischemia-reperfusion injury. Here we compared the therapeutic effects of targeting fibrin or extracellular DNA in intestinal infarction after midgut volvulus in rats. Following iatrogenic midgut volvulus induction for 3 hours, we treated animals with a combination of tissue plasminogen activator (tPA) and low molecular weight heparin (LMWH) to target fibrin or with DNase1 to degrade extracellular DNA...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133512/exosomes-from-adipose-derived-stem-cells-attenuate-adipose-inflammation-and-obesity-through-polarizing-m2-macrophages-and-beiging-in-white-adipose-tissues
#19
Hui Zhao, Qianwen Shang, Zhenzhen Pan, Yang Bai, Zequn Li, Huiying Zhang, Qiu Zhang, Chun Guo, Lining Zhang, Qun Wang
Adipose-derived stem cells (ADSCs) play critical roles in controlling obesity-associated inflammation and metabolic disorders. Exosomes from ADSCs exert protective effects in several diseases, but their roles in obesity and related pathological conditions remain unclear. Here we showed that treatment of obese mice with ADSC-derived exosomes facilitated their metabolic homeostasis including improved insulin sensitivity (27.8% improvement), reduced obesity and alleviated hepatic steatosis. ADSC-derived exosomes drove M2 macrophage polarization, inflammation reduction and beiging in white adipose tissues (WAT) of diet-induced obese mice...
November 13, 2017: Diabetes
https://www.readbyqxmd.com/read/29132172/can-screening-and-confirmatory-testing-in-the-management-of-patients-with-primary-aldosteronism-be-improved
#20
Michael Stowasser, Ashraf Ahmed, Zeng Guo, Martin Wolley, Jacobus Ungerer, Brett McWhinney, Marko Poglitsch, Richard Gordon
Widespread application of the plasma aldosterone/renin ratio (ARR) as a screening test has led to the recognition that primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension, accounting for 5-10% of patients. Maximal detection requires accurate diagnostic approaches and awareness and control of factors that confound results, including most antihypertensives, posture, time of day, dietary salt, and plasma potassium. Recent studies have revealed potential for false positives in patients on beta-adrenoceptor blockers, and, when direct renin concentration (but not plasma renin activity) is used to measure renin, in women during the luteal phase of the menstrual cycle or receiving estrogen-containing contraceptives or hormonal replacement therapy...
November 13, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
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