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https://www.readbyqxmd.com/read/29783682/heat-shock-gene-inactivation-and-protein-aggregation-with-links-to-chronic-diseases
#1
Ian James Martins
The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and autoimmunity. Overnutrition, temperature dysregulation, and stress repress the heat shock gene Sirtuin 1 with the induction of HSP regulated amyloid beta aggregation involved in the autoimmune response. Defective circadian rhythm alterations are connected to inactivation of the peripheral sink amyloid beta clearance pathway and related to insulin resistance, protein aggregation, and autoimmune disease in non-alcoholic fatty liver disease (NAFLD) and various neurodegenerative diseases such as Alzheimer's disease...
May 18, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29780805/stabilization-of-hypoxia-inducible-factor-1-alpha-augments-the-therapeutic-capacity-of-bone-marrow-derived-mesenchymal-stem-cells-in-experimental-pneumonia
#2
Naveen Gupta, Victor Nizet
Bone marrow-derived mesenchymal stem cells (MSCs) have therapeutic effects in experimental models of lung injury. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcriptional regulator that influences cellular metabolism, energetics, and survival under hypoxic conditions. The current study investigated the effects of stabilizing HIF-1α on the therapeutic capacity of MSCs in an experimental mouse model of bacterial pneumonia. HIF-1α stabilization was achieved by the small molecule prolyl-hydroxlase inhibitor, AKB-4924 (Aerpio Therapeutics, Inc...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29772289/nose-to-brain-drug-delivery-an-update-on-clinical-challenges-and-progress-towards-approval-of-anti-alzheimer-drugs
#3
REVIEW
Mukta Agrawal, Swarnlata Saraf, Shailendra Saraf, Sophia G Antimisiaris, Mahavir Chougule, Sunday A Shoyele, Amit Alexander
According to the Alzheimer Association Report (2017), Alzheimer's disease (AD) is the 6th primary cause of death in the USA, which affects nearly 5.5 million people. In the year 2017 itself, the cost of AD treatment in the USA has been reported to rise to $259 billion. This statistic shows the severity of the disease in the USA which is very much similar across the globe. On the other hand, the treatment remains limited to a few conventional oral medications (approved by FDA). These are mainly acting superficially from mild to the moderate AD...
May 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29768412/adverse-events-following-single-dose-treatment-of-lymphatic-filariasis-observations-from-a-review-of-the-literature
#4
Philip J Budge, Carly Herbert, Britt Andersen, Gary J Weil
BACKGROUND: WHO's Global Programme to Eliminate Lymphatic Filariasis (LF) uses mass drug administration (MDA) of anthelmintic medications to interrupt LF transmission in endemic areas. Recently, a single dose combination of ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB) was shown to be markedly more effective than the standard two-drug regimens (DEC or IVM, plus ALB) for achieving long-term clearance of microfilaremia. OBJECTIVE AND METHODS: To provide context for the results of a large-scale, international safety trial of MDA using triple drug therapy, we searched Ovid Medline for studies published from 1985-2017 that reported adverse events (AEs) following treatment of LF with IVM, DEC, ALB, or any combination of these medications...
May 16, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29768205/c-elegans-blastomeres-clear-the-corpse-of-the-second-polar-body-by-lc3-associated-phagocytosis
#5
Gholamreza Fazeli, Maurice Stetter, Jaime N Lisack, Ann M Wehman
To understand how undifferentiated pluripotent cells cope with cell corpses, we examined the clearance of polar bodies born during female meiosis. We found that polar bodies lose membrane integrity and expose phosphatidylserine in Caenorhabditis elegans. Polar body signaling recruits engulfment receptors to the plasma membrane of embryonic blastomeres using the PI3K VPS-34, RAB-5 GTPase and the sorting nexin SNX-6. The second polar body is then phagocytosed using receptor-mediated engulfment pathways dependent on the Rac1 ortholog CED-10 but undergoes non-apoptotic programmed cell death independent of engulfment...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29765590/a-case-of-rhabdomyolysis-after-kidney-transplantation-successfully-managed-with-intensive-continuous-dialysis
#6
Rauf Shahbazov, Michael Fox, Jennifer L Alejo, Malik A Anjum, Feredun Azari, Alden Doyle, Avinash Agarwal, Kenneth L Brayman
Rhabdomyolysis is characterized by muscle cell death which can result in acute kidney injury from pigment nephropathy. We present a patient who developed rhabdomyolysis immediately after deceased donor kidney transplantation surgery and was managed with continuous renal replacement therapy that resulted in successful salvage of the kidney allograft. Patients who develop acute kidney failure requiring renal replacement therapy generally have a poor prognosis. It is worth noting that while continuous veno-venous hemofiltration (CVVHF) offers greater volume support and continuous clearance compared to hemodialysis (HD), recent studies have demonstrated no clinically significant improvement in clinical outcome between the two...
April 2018: Journal of Surgical Case Reports
https://www.readbyqxmd.com/read/29761371/tolerability-and-efficacy-of-deferasirox-in-patients-with-transfusional-iron-overload-results-from-a-german-2-year-non-interventional-study
#7
Florian Nolte, Holger Nückel, Burkhard Schmidt, Thomas Geer, Oleg Rubanov, Holger Hebart, Andrea Jarisch, Stefan Albrecht, Christiane Johr, Christiane Schumann, Wolf-Karsten Hofmann
BACKGROUND: Iron overload (IOL) due to repetitive transfusions of packed red blood cells (pRBC) has a major impact on morbidity and mortality in patients with inherited bone marrow failure syndromes and hemoglobinopathies such as thalassemia and sickle cell disease. However, whether IOL influences the outcome of elderly patients with myeloid malignancies is not yet clear. Moreover, clinical trials have reported high drop-out rates during treatment with the oral iron chelator deferasirox (DFX)...
May 14, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29760395/silver-nanoparticles-promote-the-emergence-of-heterogeneic-human-neutrophil-sub-populations
#8
Jennifer A Fraser, Sadie Kemp, Lesley Young, Mark Ross, Morag Prach, Gary R Hutchison, Eva Malone
Neutrophil surveillance is central to nanoparticle clearance. Silver nanoparticles (AgNP) have numerous uses, however conflicting evidence exists as to their impact on neutrophils and whether they trigger damaging inflammation. Neutrophil's importance in innate defence and regulating immune networks mean it's essential we understand AgNP's impact on neutrophil function. Human neutrophil viability following AgNP or Ag Bulk treatment was analysed by flow cytometry and AnV/PI staining. Whilst AgNP exposure did not increase the total number of apoptotic neutrophils, the number of late apoptotic neutrophils was increased, suggesting AgNP increase transit through apoptosis...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760178/region-and-activity-dependent-regulation-of-extracellular-glutamate
#9
Nawrin F Pinky, Crystal M Wilkie, Jocelyn R Barnes, Matthew P Parsons
Transporter-mediated glutamate uptake plays an essential role in shaping synaptic neurotransmission. The rapid removal of synaptically-released glutamate ensures the high temporal dynamics characteristic of fast excitatory chemical neurotransmission and prevents the overexcitation of extrasynaptic NMDA receptors that have been implicated in synaptic plasticity impairments and cell death. Despite clear regional differences in plasticity and excitotoxic thresholds, few studies have compared extracellular glutamate dynamics across different brain regions and in response to a range of neural activity including plasticity-inducing stimuli...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29755319/ambra1-mediated-mitophagy-counteracts-oxidative-stress-and-apoptosis-induced-by-neurotoxicity-in-human-neuroblastoma-sh-sy5y-cells
#10
Anthea Di Rita, Pasquale D'Acunzo, Luca Simula, Silvia Campello, Flavie Strappazzon, Francesco Cecconi
Therapeutic strategies are needed to protect dopaminergic neurons in Parkinson's disease (PD) patients. Oxidative stress caused by dopamine may play an important role in PD pathogenesis. Selective autophagy of mitochondria (mitophagy), mainly regulated by PINK1 and PARKIN, plays an important role in the maintenance of cell homeostasis. Mutations in those genes cause accumulation of damaged mitochondria, leading to nigral degeneration and early-onset PD. AMBRA1ActA is a fusion protein specifically expressed at the mitochondria, and whose expression has been shown to induce a powerful mitophagy in mammalian cells...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29746472/differential-t-cell-response-against-bk-virus-regulatory-and-structural-antigens-a-viral-dynamics-modelling-approach
#11
Arturo Blazquez-Navarro, Thomas Schachtner, Ulrik Stervbo, Anett Sefrin, Maik Stein, Timm H Westhoff, Petra Reinke, Edda Klipp, Nina Babel, Avidan U Neumann, Michal Or-Guil
BK virus (BKV) associated nephropathy affects 1-10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot) in six patients with BKV associated nephropathy using ODE modelling...
May 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29740404/inhalational-gentamicin-treatment-is-effective-against-pneumonic-plague-in-a-mouse-model
#12
David Gur, Itai Glinert, Moshe Aftalion, Yaron Vagima, Yinon Levy, Shahar Rotem, Ayelet Zauberman, Avital Tidhar, Arnon Tal, Sharon Maoz, Raphael Ber, Avi Pass, Emanuelle Mamroud
Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, Yersinia pestis (Y. pestis) , is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therapeutic window after symptom onset. However, the non-specific "flu-like" symptoms often lead to delayed diagnosis and therapy. In this study, we evaluated inhalational gentamicin therapy in an infected mouse model as a means to improve antibiotic treatment efficacy...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29738881/rhim-based-protein-protein-interactions-in-anti-microbial-defence-against-programmed-cell-death-by-necroptosis
#13
REVIEW
Max O D G Baker, Nirukshan Shanmugam, Chi L L Pham, Merryn Strange, Megan Steain, Margaret Sunde
The Receptor-interacting protein kinase Homotypic Interaction Motif (RHIM) is an amino acid sequence that mediates multiple protein:protein interactions in the mammalian programmed cell death pathway known as necroptosis. At least one key RHIM-based complex has been shown to have a functional amyloid fibril structure, which provides a stable hetero-oligomeric platform for downstream signaling. RHIMs and related motifs are present in immunity-related proteins across nature, from viruses to fungi to metazoans...
May 5, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29736957/functional-up-regulation-of-the-m-current-by-retigabine-contrasts-hyperexcitability-and-excitotoxicity-on-rat-hypoglossal-motoneurons
#14
Filippo Ghezzi, Laura Monni, Andrea Nistri
KEY POINT SUMMARY: Excessive neuronal excitability characterizes several neuropathological conditions including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Hypoglossal motoneurons (HMs) that control tongue muscles, are extremely vulnerable to this disease and undergo damage and death when exposed to excessive glutamate extracellular concentration that causes excitotoxicity. Our laboratory devised an in vitro model of excitotoxicity obtained by pharmacological block of glutamate transporters...
May 7, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29721243/opportunistic-infections-in-end-stage-liver-disease
#15
Michele Bartoletti, Maddalena Giannella, Sara Tedeschi, Pierluigi Viale
Liver cirrhosis is the 10th most common cause of death in Western world and infection is associated with a high morbidity and mortality, and represents the leading cause of acute liver decompensation. Patients with end-stage liver disease exhibit an important impairment of immune system. This condition, called cirrhosis-associated immune dysfunction, summarizes both local and systemic immune system alterations in liver cirrhosis that play a pivotal role in determining both the high incidence of infections and the ominous infections related mortality in this population...
March 29, 2018: Infectious Disease Reports
https://www.readbyqxmd.com/read/29714486/melanoma-imaging-using-18-f-labeled-%C3%AE-melanocyte-stimulating-hormone-derivatives-with-positron-emission-tomography
#16
Chengcheng Zhang, Zhengxing Zhang, Kuo-Shyan Lin, Joseph Lau, Jutta Zeisler, Nadine Colpo, David M Perrin, Francois Benard
Melanocortin 1 receptor (MC1R) is specifically expressed in the majority of melanomas, a leading cause of death related to skin cancers. Accurate staging and early detection is crucial in managing melanoma. Based on the α-melanocyte-stimulating hormone (αMSH) sequence, MC1R-targeted peptides have been studied for melanoma imaging, predominately for use with single-photon emission computed tomography (SPECT), with few attempts made for positron emission tomography (PET). 18 F is a commonly used PET isotope due to readily available cyclotron production, pure positron emission and a favorable half-life (109...
May 1, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29707136/bnip3-modulates-the-interface-between-b16-f10-melanoma-cells-and-immune-cells
#17
Erminia Romano, Nicole Rufo, Hannelie Korf, Chantal Mathieu, Abhishek D Garg, Patrizia Agostinis
The hypoxia responsive protein BNIP3, plays an important role in promoting cell death and/or autophagy, ultimately resulting in a cancer type-dependent, tumour-enhancer or tumour-suppressor activity. We previously reported that in melanoma cells, BNIP3 regulates cellular morphology, mitochondrial clearance, cellular viability and maintains protein expression of CD47, a pro-cancerous, immunosuppressive 'don't eat me' signal. Surface exposed CD47 is often up-regulated by cancer cells to avoid clearance by phagocytes and to suppress immunogenic cell death (ICD) elicited by anticancer therapies...
April 3, 2018: Oncotarget
https://www.readbyqxmd.com/read/29698625/sphingolipids-as-targets-for-inhalation-treatment-of-cystic-fibrosis
#18
Katrin Anne Becker, Joachim Riethmüller, Aaron P Seitz, Aaron Gardner, Ryan Boudreau, Markus Kamler, Burkhard Kleuser, Edward Schuchman, Charles C Caldwell, Michael J Edwards, Heike Grassmé, Malcolm Brodlie, Erich Gulbins
Studies over the past several years have demonstrated the important role of sphingolipids in cystic fibrosis (CF), chronic obstructive pulmonary disease and acute lung injury. Ceramide is increased in airway epithelial cells and alveolar macrophages of CF mice and humans, while sphingosine is dramatically decreased. This increase in ceramide results in chronic inflammation, increased death of epithelial cells, release of DNA into the bronchial lumen and thereby an impairment of mucociliary clearance; while the lack of sphingosine in airway epithelial cells causes high infection susceptibility in CF mice and possibly patients...
April 24, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29688442/impact-of-residual-kidney-function-on-hemodialysis-adequacy-and-patient-survival
#19
Mengjing Wang, Yoshitsugu Obi, Elani Streja, Connie M Rhee, Jing Chen, Chuanming Hao, Csaba P Kovesdy, Kamyar Kalantar-Zadeh
Background: Both dialysis dose and residual kidney function (RKF) contribute to solute clearance and are associated with outcomes in hemodialysis patients. We hypothesized that the association between dialysis dose and mortality is attenuated with greater RKF. Methods: Among 32 251 incident hemodialysis patients in a large US dialysis organization (2007-11), we examined the interaction between single-pool Kt/V (spKt/V) and renal urea clearance (rCLurea) levels in survival analyses using multivariable Cox proportional hazards regression model...
April 23, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29686673/the-cd8-t-cell-response-to-respiratory-virus-infections
#20
REVIEW
Megan E Schmidt, Steven M Varga
Humans are highly susceptible to infection with respiratory viruses including respiratory syncytial virus (RSV), influenza virus, human metapneumovirus, rhinovirus, coronavirus, and parainfluenza virus. While some viruses simply cause symptoms of the common cold, many respiratory viruses induce severe bronchiolitis, pneumonia, and even death following infection. Despite the immense clinical burden, the majority of the most common pulmonary viruses lack long-lasting efficacious vaccines. Nearly all current vaccination strategies are designed to elicit broadly neutralizing antibodies, which prevent severe disease following a subsequent infection...
2018: Frontiers in Immunology
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