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https://www.readbyqxmd.com/read/28821999/developmental-neurotoxicity-of-the-hippocampus-following-in-utero-exposure-to-methylmercury-impairment-in-cell-signaling
#1
Luana Heimfarth, Jeferson Delgado, Moara Rodrigues Mignori, Daniel Pens Gelain, José Cláudio Fonseca Moreira, Regina Pessoa-Pureur
In this study, we assessed some hippocampal signaling cascades and behavioral impairments in 30-day-old rat pups prenatally exposed to methylmercury (MeHg). Pregnant rats were exposed to 1.0 or 2.0 mg/kg MeHg by gavage in alternated days from gestational day 5 until parturition. We found increased anxiety-like and decreased exploration behavior evaluated by open field test and deficit of both short- and long-term memories by novel object recognition task, respectively, in MeHg-treated pups. Downregulated PI3K/Akt/mTOR pathway and activated/hypophosphorylated (Ser9) GSK3β in MeHg-treated pups could be upstream of hyperphosphorylated Tau (Ser396) destabilizing microtubules and contributing to neural dysfunction in the hippocampus of these rats...
August 18, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28821969/interleukin-1-receptor-like-1-protein-st2-is-a-potential-biomarker-for-cardiomyopathy-in-duchenne-muscular-dystrophy
#2
Julia Anderson, Haeri Seol, Heather Gordish-Dressman, Yetrib Hathout, Christopher F Spurney
Duchenne muscular dystrophy (DMD) is a rare, fatal X-linked disorder characterized by the lack of dystrophin, a key sarcolemma muscle protein. Cardiac failure is a significant cause of death in DMD subjects. The purpose of our research was to identify potential cardiac serum biomarkers associated with DMD cardiomyopathy. This is an observational, case-controlled study using subjects from the CINRG DMD natural history study with cardiomyopathy (ejection fraction (EF) <55%; shortening fraction (SF) <28%), subjects without cardiomyopathy (EF ≥ 55%; SF ≥ 28%) compared to normal healthy volunteer subjects...
August 18, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28821644/calpain-dependent-degradation-of-nucleoporins-contributes-to-motor-neuron-death-in-a-mouse-model-of-chronic-excitotoxicity
#3
Kaori Sugiyama, Tomomi Aida, Masatoshi Nomura, Ryoichi Takayanagi, Hanns U Zeilhofer, Kohichi Tanaka
Glutamate-mediated excitotoxicity induces neuronal death by altering various intracellular signaling pathways and is implicated as a common pathogenic pathway in many neurodegenerative diseases. In the case of motor neuron disease, there is significant evidence to suggest that overactivation of AMPA receptors due to deficiencies in the expression and function of glial glutamate transporter GLT1 and GLAST plays an important role in the mechanisms of neuronal death. However, a causal role for glial glutamate transporter dysfunction in motor neuron death remains unknown...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821633/cell-autonomous-cytotoxicity-of-type-i-interferon-response-via-induction-of-endoplasmic-reticulum-stress
#4
Chrysovalantou Mihailidou, Athanasios G Papavassiliou, Hippokratis Kiaris
The interaction of IFN with specific membrane receptors that transduce death-inducing signals is considered to be the principle mechanism of IFN-induced cytotoxicity. In this study, the classic non-cell-autonomous cytotoxicity of IFN was augmented by cell-autonomous mechanisms that operated independently of the interaction of IFN with its receptors. Cells primed to produce IFN by 5-azacytidine (5-aza) underwent endoplasmic reticulum (ER) stress. The chemical chaperones tauroursodeoxycholate (TUDCA) and 4-phenylbutyrate (4-PBA), as well as the iron chelator ciclopirox (CPX), which reduces ER stress, alleviated the cytotoxicity of 5-aza...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821620/arjunolic-acid-a-peroxisome-proliferator-activated-receptor-alpha-agonist-regresses-cardiac-fibrosis-by-inhibiting-non-canonical-tgf-%C3%AE-signaling
#5
Trisha Bansal, Emeli Chatterjee, Jasdeep Singh, Arjun Ray, Bishwajit Kundu, V Thankamani, Shantanu Sengupta, Sagartirtha Sarkar
Cardiac hypertrophy and associated heart fibrosis remain a major cause of death worldwide. Phytochemicals have gained attention as alternative therapeutics for managing cardiovascular diseases. These include the extract from the plant Terminalia arjuna which is a popular cardioprotectant and may prevent or slow progression of pathological hypertrophy to heart failure. Here, we investigated the mode of action of a principal bioactive T. arjuna compound, arjunolic acid (AA) in ameliorating hemodynamic load-induced cardiac fibrosis and identified its intracellular target...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821560/optoacoustic-detection-of-early-therapy-induced-tumor-cell-death-using-a-targeted-imaging-agent
#6
Bangwen Xie, Michal R Tomaszewski, Andre Neves, Susana Ros, De-En Hu, Sarah McGuire, Stefanie Roshy Mullins, David A Tice, Richard C A Sainson, Sarah E Bohndiek, Robert W Wilkinson, Kevin M Brindle
The development of new treatments and their deployment in the clinic may be assisted by imaging methods that allow an early assessment of treatment response in individual patients. The C2A domain of Synaptotagmin-I (C2Am), which binds to the phosphatidylserine (PS) exposed by apoptotic and necrotic cells, has been developed as an imaging probe for detecting cell death. Multispectral optoacoustic tomography (MSOT) is a real-time and clinically applicable imaging modality that was used here with a near infrared (NIR) fluorophore-labeled C2Am to image tumor cell death in mice treated with a TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2) agonist and with 5-fluorouracil (5-FU)...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28820880/knock-out-of-a-mitochondrial-sirtuin-protects-neurons-from-degeneration-in-caenorhabditis-elegans
#7
Rachele Sangaletti, Massimo D'Amico, Jeff Grant, David Della-Morte, Laura Bianchi
Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis...
August 18, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28820571/comparison-of-spreading-depolarizations-in-the-motor-cortex-and-nucleus-accumbens-similar-patterns-of-oxygen-responses-and-the-role-of-dopamine
#8
Caddy Noahl Hobbs, Gordon Holzberg, Akira S Min, R Mark Wightman
Spreading depolarizations (SD) are pathophysiological phenomena that spontaneously arise in traumatized neural tissue and can promote cellular death. Most investigations of SD are performed in the cortex, a brain region that is susceptible to these depolarizing waves and accessible via a variety of monitoring techniques. Here, we describe SD responses in the cortex and the deep brain region of the nucleus accumbens (NAc) of the anesthetized rat with a minimally invasive, implantable sensor. With high temporal resolution, we characterize the time course of oxygen responses to SD in relation to the electrophysiological depolarization signal...
August 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28819122/anti-inflammatory-drugs-suppress-ultrasound-mediated-mesenchymal-stromal-cell-tropism-to-kidneys
#9
Scott R Burks, Ben A Nguyen, Michele N Bresler, Matthew E Nagle, Saejeong J Kim, Joseph A Frank
Mesenchymal stromal cells (MSC) are potential renal therapeutics. Clinically, results are mixed partly because MSC tropism to kidneys is minimal following infusion. Ultrasound augmentation of the renal microenvironment is becoming increasingly-important in renal MSC therapies. We demonstrated pulsed-focused-ultrasound (pFUS) increases enhanced homing permeability and retention of MSC in mouse kidneys. Here, we characterized the temporal proteomic response to pFUS in mouse kidneys and its association with MSC tropism...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817786/propofol-attenuates-bv2-microglia-inflammation-via-nmda-receptor-inhibition
#10
Qichao Wu, Yanjun Zhao, Xiangyuan Chen, Minmin Zhu, Changhong Miao
Activated microglia, involved in the occurrence and improvement of sepsis-associated encephalopathy, can induce the expression of pro-inflammatory cytokines and pro-inflammatory enzymes, resulting in inflammation-mediated neuronal cell death. It was reported that propofol could inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and pro-inflammatory enzymes expression in BV2 and primary microglial cells. However, the underlying mechanism is not well known. In the present study, we investigated whether and how propofol inhibited LPS-induced the expression of pro-inflammatory cytokines and pro-inflammatory enzymes in BV2 cells...
August 17, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28817373/cabozantinib-as-salvage-therapy-for-patients-with-tyrosine-kinase-inhibitor-refractory-differentiated-thyroid-cancer-results-of-a-multicenter-phase-ii-international-thyroid-oncology-group-trial
#11
Maria E Cabanillas, Jonas A de Souza, Susan Geyer, Lori J Wirth, Michael E Menefee, Stephen V Liu, Komal Shah, John Wright, Manisha H Shah
Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817116/total-tanshinones-exhibits-anti-inflammatory-effects-through-blocking-tlr4-dimerization-via-the-myd88-pathway
#12
Hongwei Gao, Xin Liu, Wen Sun, Naixin Kang, Yanli Liu, Shilin Yang, Qiong-Ming Xu, Chunming Wang, Xiuping Chen
Tanshinones belong to a group of lipophilic constituents of Salvia miltiorrhiza Bunge (Danshen), which is widely used in traditional Chinese medicine. A deluge of studies demonstrated that tanshinones exert anti-inflammatory effects, but the underlying mechanisms remain unclear to date. This study investigated the anti-inflammatory effects and mechanisms of total tanshinones (TTN). TTN suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the secretion of TNF-α, IL-6, and IL-1β in RAW264...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28816642/proteomic-analysis-of-the-human-olfactory-bulb
#13
Manjunath Dammalli, Gourav Dey, Anil K Madugundu, Manish Kumar, Benvil Rodrigues, Harsha Gowda, Bychapur Gowrishankar Siddaiah, Anita Mahadevan, Susarla Krishna Shankar, Thottethodi Subrahmanya Keshava Prasad
The importance of olfaction to human health and disease is often underappreciated. Olfactory dysfunction has been reported in association with a host of common complex diseases, including neurological diseases such as Alzheimer's disease and Parkinson's disease. For health, olfaction or the sense of smell is also important for most mammals, for optimal engagement with their environment. Indeed, animals have developed sophisticated olfactory systems to detect and interpret the rich information presented to them to assist in day-to-day activities such as locating food sources, differentiating food from poisons, identifying mates, promoting reproduction, avoiding predators, and averting death...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28815913/metastatic-triple-negative-breast-cancer-optimizing-treatment-options-new-and-emerging-targeted-therapies
#14
REVIEW
Parham Khosravi-Shahi, Luis Cabezón-Gutiérrez, Sara Custodio-Cabello
Triple negative breast cancer (TNBC) is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. It also has a distinct epidemiology. TNBCs are frequently of high histologic grade, typically more aggressive and difficult to treat than hormone receptor-positive tumors, and they are associated with a higher risk of early relapse with visceral metastasis after surgery, chemotherapy and/or radiotherapy. The lack of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression precludes the use of targeted therapies in advanced stages, and the only approved systemic treatment option is chemotherapy with or without bevacizumab...
August 16, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28815598/lpa1-is-a-key-mediator-of-intracellular-signalling-and-neuroprotection-triggered-by-tetracyclic-antidepressants-in-hippocampal-neurons
#15
Maria C Olianas, Simona Dedoni, Pierluigi Onali
Both lysophosphatidic acid (LPA) and antidepressants have been shown to affect neuronal survival and differentiation, but whether LPA signalling participates in the action of antidepressants is still unknown. In the present study we examined the role of LPA receptors in the regulation of ERK1/2 activity and neuronal survival by the tetracyclic antidepressants mianserin and mirtazapine in hippocampal neurons. In HT22 immortalized hippocampal cells antidepressants and LPA induced a time- and concentration-dependent stimulation of ERK1/2 phosphorylation...
August 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28815448/-1-h-15-n-and-13-c-chemical-shift-assignments-of-the-c-terminal-domain-of-tradd
#16
Ning Zhang, Wensu Yuan, Jing-Song Fan, Zhi Lin
The tumor necrosis factor receptor-associated death domain protein, TRADD, is a multifunctional intracellular molecule participating in divergent signaling pathways, such as NF-κB and apoptosis. TRADD consists of two structurally distinct domains. Its N-terminal domain displays an α-β plaits fold while its C-terminal domain belongs to the death domain (DD) superfamily. TRADD DD is a central component in the tumor necrosis factor receptor 1 signaling. It interacts with other DD-containing proteins through homotypic interactions...
August 16, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28815407/efficacy-and-safety-of-the-early-use-of-v2-receptor-antagonists-in-elderly-patients-with-decompensated-heart-failure
#17
Ryuichi Matsukawa, Toru Kubota, Masanori Okabe, Yusuke Yamamoto, Hiroshi Meno
We recently reported that the early initiation of tolvaptan in congestive heart failure shortened the hospital stay and reduced the rate of in-hospital death. However, whether or not these results apply to elderly patients with congestive heart failure is unclear. We performed a sub-analysis of our previous study. Among the 102 patients in that study, we retrospectively analyzed the elderly patients >75 years of age treated with tolvaptan. First, we analyzed the efficacy of early tolvaptan use in these patients...
August 16, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28814985/activation-of-endocannabinoid-receptor-2-as-a-mechanism-of-propofol-pretreatment-induced-cardioprotection-against-ischemia-reperfusion-injury-in-rats
#18
Hai-Jing Sun, Yan Lu, Hao-Wei Wang, Hao Zhang, Shuang-Ran Wang, Wen-Yun Xu, Hai-Long Fu, Xue-Ya Yao, Feng Yang, Hong-Bin Yuan
Propofol pretreatment before reperfusion, or propofol conditioning, has been shown to be cardioprotective, while its mechanism is unclear. The current study investigated the roles of endocannabinoid signaling in propofol cardioprotection in an in vivo model of myocardial ischemia/reperfusion (I/R) injury and in in vitro primary cardiomyocyte hypoxia/reoxygenation (H/R) injury. The results showed that propofol conditioning increased both serum and cell culture media concentrations of endocannabinoids including anandamide (AEA) and 2-arachidonoylglycerol (2-AG) detected by LC-MS/MS...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28814080/drug-delivery-from-a-multi-faceted-ultrasound-contrast-agent-influence-of-shell-composition
#19
Lauren J Jablonowski, Nutte T Teraphongphom, Margaret A Wheatley
Many cancer therapy regimes still rely heavily on the systemic administration of toxic chemotherapeutic agents. Ultrasound contrast agents consisting of microbubbles (MB) have emerged as a drug delivery vehicle to overcome the challenges associated with systemic chemotherapy. Here we describe the development of non-immunogenic, functionalized polylactic acid (PLA) MB for use in targeted cancer therapy. Our previous studies have shown that the balance between acoustic behavior and improved immune avoidance was scalable and successful to different degrees with two different PEGylation methods, and was best achieved using incorporation of PEG-PLA at 5 wt% and for a LipidPEG at 1 wt%...
August 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28812970/indole-3-carbinol-induces-g1-cell-cycle-arrest-and-apoptosis-through-aryl-hydrocarbon-receptor-in-thp-1-monocytic-cell-line
#20
Saeed Mohammadi, Fakhri Sadat Seyedhosseini, Nasser Behnampour, Yaghoub Yazdani
OBJECTIVES: The role of aryl hydrocarbon receptor (AhR) in carcinogenesis has been studied recently. Indole-3-carbinol (I3C) is an AhR agonist and a potential anticancer agent. Here, we investigated the effects of I3C on cell cycle progression and apoptosis through activation of AhR on THP-1 acute myeloid leukemia (AML) cell line. METHODS: MTT viability assay was used to measure the cytotoxic effects of I3C on THP-1 cells. Apoptosis and cell cycle assays were investigated using flow cytometry...
October 2017: Journal of Receptor and Signal Transduction Research
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