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https://www.readbyqxmd.com/read/29240283/proximal-tubular-epithelial-cells-preferentially-endocytose-covalently-modified-albumin-compared-to-native-albumin
#1
Nguyen D K Ly, Greg H Tesch, David J Nikolic-Paterson, Philip Poronnik
AIM: Albumin can be covalently modified at surface lysine residues and thus the circulation contains a mixture of native albumin (i.e. not modified) and albumin with varying degrees of modification. Uptake and lysosomal degradation of glomerular filtered albumin by proximal tubular cells via the megalin scavenger receptor is considered an important mechanism to limit albumin loss in the urine. However, whether this is a general mechanism of tubular uptake of albumin or if this is restricted to modified albumin is unknown...
December 14, 2017: Nephrology
https://www.readbyqxmd.com/read/29240051/influence-of-autophagy-on-the-genesis-and-development-of-atherosclerosis-and-its-risk-factors
#2
M A Sazonova, V V Sinev, V P Karagodin, A I Ryzhkova, E V Galitsyna, V A Barinova, R I Zelinyĭ, N A Nikitina, A N Orekhov
Autophagy is a highly conservative process of degeneration during which intracellular components including soluble macromolecules (e. g., nucleic acids, proteins, carbohydrates and lipids) and dysfunctional organelles (e. g., mitochondria, peroxisomes, and the endoplasmatic reticulum) are degraded by a lysosome. Autophagy serves as a dynamic system of recycling proving cells with energy and building components. Because of it in cells of an organism new proteins and membranes can form contributing to survival of the individual under starvation conditions...
2017: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/29239454/organelle-targeting-surface-enhanced-raman-scattering-sers-nanosensors-for-subcellular-ph-sensing
#3
Yanting Shen, Lijia Liang, Shuqin Zhang, Dianshuai Huang, Jing Zhang, Shuping Xu, Chongyang Liang, Weiqing Xu
The pH value of subcellular organelles in living cells is a significant parameter in the physiological activities of cells. Its abnormal fluctuations are commonly believed to be associated with cancers and other diseases. Herein, a series of surface-enhanced Raman scattering (SERS) nanosensors with high sensitivity and targeting function was prepared for the quantification and monitoring of pH values in mitochondria, nucleus, and lysosome. The nanosensors were composed of gold nanorods (AuNRs) functionalized with a pH-responsive molecule (4-mercaptopyridine, MPy) and peptides that could specifically deliver the AuNRs to the targeting subcellular organelles...
December 14, 2017: Nanoscale
https://www.readbyqxmd.com/read/29239447/carbon-nanotubes-as-nanovectors-for-intracellular-delivery-of-laronidase-in-mucopolysaccharidosis-type-i
#4
T Da Ros, A Ostric, F Andreola, M Filocamo, M Pietrogrande, F Corsolini, M Stroppiano, S Bruni, A Serafino, S Fiorito
The immobilization of proteins on carbon nanotubes (CNTs) has been widely reported mainly for the preparation of sensors while the conjugation of enzymes for therapeutic purposes has scarcely been considered. Herein we report, to the best of our knowledge, the first example of intracellular delivery of a therapeutic enzyme by means of CNTs, retaining its activity. Mucopolysaccharidosis I is a rare genetic disease characterized by the deficiency or absence of the activity of the α-l-iduronidase (IDUA) enzyme...
December 14, 2017: Nanoscale
https://www.readbyqxmd.com/read/29239314/taking-out-the-garbage-cathepsin-d-and-calcineurin-in-neurodegeneration
#5
REVIEW
Andreas Aufschnaiter, Verena Kohler, Sabrina Büttner
Cellular homeostasis requires a tightly controlled balance between protein synthesis, folding and degradation. Especially long-lived, post-mitotic cells such as neurons depend on an efficient proteostasis system to maintain cellular health over decades. Thus, a functional decline of processes contributing to protein degradation such as autophagy and general lysosomal proteolytic capacity is connected to several age-associated neurodegenerative disorders, including Parkinson's, Alzheimer's and Huntington's diseases...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29238336/combination-of-classifiers-identifies-fungal-specific-activation-of-lysosome-genes-in-human-monocytes
#6
João P Leonor Fernandes Saraiva, Cristina Zubiria-Barrera, Tilman E Klassert, Maximilian J Lautenbach, Markus Blaess, Ralf A Claus, Hortense Slevogt, Rainer König
Blood stream infections can be caused by several pathogens such as viruses, fungi and bacteria and can cause severe clinical complications including sepsis. Delivery of appropriate and quick treatment is mandatory. However, it requires a rapid identification of the invading pathogen. The current gold standard for pathogen identification relies on blood cultures and these methods require a long time to gain the needed diagnosis. The use of in situ experiments attempts to identify pathogen specific immune responses but these often lead to heterogeneous biomarkers due to the high variability in methods and materials used...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29238189/diethyl-citrate-and-sodium-citrate-reduce-the-cytotoxic-effects-of-nanosized-hydroxyapatite-crystals-on-mouse-vascular-smooth-muscle-cells
#7
Chong-Yu Zhang, Xin-Yuan Sun, Jian-Ming Ouyang, Bao-Song Gui
Objective: This study aimed to investigate the damage mechanism of nanosized hydroxyapatite (nano-HAp) on mouse aortic smooth muscle cells (MOVASs) and the injury-inhibiting effects of diethyl citrate (Et2Cit) and sodium citrate (Na3Cit) to develop new drugs that can simultaneously induce anticoagulation and inhibit vascular calcification. Methods: The change in cell viability was evaluated using a cell proliferation assay kit, and the amount of lactate dehydrogenase (LDH) released was measured using an LDH kit...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29238000/elevation-of-serum-acid-sphingomyelinase-activity-in-children-with-acute-respiratory-syncytial-virus-bronchiolitis
#8
Shuichiro Yoshida, Atsuko Noguchi, Wataru Kikuchi, Hiroshi Fukaya, Kiyoshi Igarashi, Tsutomu Takahashi
Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29237927/distinct-rab7-related-endosomal-autophagic-lysosomal-dysregulation-observed-in-cortex-and-hippocampus-in-appswe-psen1de9-mouse-model-of-alzheimer-s-disease
#9
Li Ba, Xiao-Hua Chen, Yan-Lin Chen, Qing Nie, Zhi-Jun Li, Feng-Fei Ding, Min Zhang
BACKGROUND: Amyloid-β deposition and accumulation of autophagic vacuoles are pathologic features of Alzheimer's disease (AD). Dysregulation of the endosomal-autophagic-lysosomal (EAL) pathway, which impairs amyloid precursor protein processing, is one of the earliest changes in AD. However, the precise role of EAL pathway in neurodegeneration remains unclear. This study aimed to investigate the role of EAL pathway in AD and further study the mechanism of EAL dysfunction. METHODS: We used 3-, 7-, and 12-month-old APPswe/PSEN1dE9 (APP/PS1) mice to model different stages of AD with age- and gender-matched wild-type littermates as controls (4-7 mice per group) and detected the changes of EAL markers, endosomal organizers Rab5 and Rab7, autophagosome marker LC3B, and lysosomal proteins Lamp1/2 in cortex and hippocampus by immunohistochemistry and Western blotting analysis...
December 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29237845/human-cytomegalovirus-replication-is-inhibited-by-the-autophagy-inducing-compounds-trehalose-and-smer28-through-distinctively-different-mechanisms
#10
Alex E Clark, Maite Sabalza, Philip L S M Gordts, Deborah H Spector
Human Cytomegalovirus (HCMV) is the top viral cause of birth defects worldwide, and current therapies have high toxicity. We previously published that the mTOR-independent autophagy-inducing disaccharide trehalose inhibits HCMV replication in multiple cell types. Here, we examine the mechanism of inhibition and introduce the autophagy inducer SMER28 as an additional inhibitor of HCMV acting through a different mechanism. We find that trehalose induces vacuolation and acidification of vacuoles, and that debris, including debris consistent in appearance with abnormal virions, is present in multivesicular bodies...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237821/sequential-actions-of-phosphatidylinositol-phosphates-regulate-phagosome-lysosome-fusion
#11
Andreas Jeschke, Albert Haas
Phagosomes mature into phagolysosomes by sequential fusion with early endosomes, late endosomes, and lysosomes. Phagosome-with-lysosome fusion (PLF) results in the delivery of lysosomal hydrolases into phagosomes and in digestion of the cargo. The machinery that drives PLF has been little investigated. Using a cell-free system, we recently identified the phosphoinositide lipids (PIPs) phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 4-phosphate [PI(4)P] as regulators of PLF. We now report the identification and the PIP requirements of four distinct sub-reactions of PLF...
December 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29237663/progressive-myoclonic-epilepsy-and-horizontal-gaze-palsy-a-rare-aetiology
#12
Rajveer Singh, Aditya Choudhary, Amith S Kumar, Manoj Kumar Goyal
Gaucher's disease is a rare autosomal recessive, potentially fatal disorder but most common type among lysosomal storage disorders. The disease's incidence is around 1/40 000 to 1/60 000 births in the general population. A 32-year-old man, born out of non-consanguineous union, presented with generalised tonic-clonic seizures and myoclonus since 17 years of age. Seizures were noted to be resistant to multiple epileptic drugs. He developed gait imbalance, intentional tremor and dysarthria. Detailed examination revealed hepatosplenomegaly, bilateral pancerebellar signs with normal power, reflexes and sensory system...
December 13, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29237570/synergistic-enhancement-of-anticancer-therapeutic-efficacy-of-hpma-copolymer-doxorubicin-conjugates-via-combination-of-ligand-modification-and-stimuli-response-srategies
#13
Lian Li, Minglu Zhou, Yuan Huang
N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer has been extensively studied as drug carrier for tumor therapy. Due to the Enhanced Permeability and Retention (EPR) effect, HPMA copolymer drug conjugates are able to be passively accumulated in the tumor site. Currently, efficient uptake of this polymeric system by the cancer cells remains a big challenge, as HPMA polymer is highly hydrophilic, neutrally charged, and has low affinity towards cell membrane. In this study, selective and enhanced intracellular internalization of the copolymer-drug conjugates was achieved by utilizing a hybrid strategy including ligand modification and stimuli response...
December 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29237114/emerging-paradigm-of-crosstalk-between-autophagy-and-the-ubiquitin-proteasome-system
#14
Taewook Nam, Jong Hyun Han, Sushil Devkota, Han-Woong Lee
Cellular protein homeostasis is maintained by two major degradation pathways, namely the ubiquitin-proteasome system (UPS) and autophagy. Until recently, the UPS and autophagy were considered to be largely independent systems targeting proteins for degradation in the proteasome and lysosome, respectively. However, the identification of crucial roles of molecular players such as ubiquitin and p62 in both of these pathways as well as the observation that blocking the UPS affects autophagy flux and vice versa has generated interest in studying crosstalk between these pathways...
December 12, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/29236977/gene2drug-a-computational-tool-for-pathway-based-rational-drug-repositioning
#15
Francesco Napolitano, Diego Carrella, Barbara Mandriani, Sandra Pisonero, Francesco Sirci, Diego Medina, Nicola Brunetti-Pierri, Diego di Bernardo
Motivation: Drug repositioning has been proposed as an effective shortcut to drug discovery. The availability of large collections of transcriptional responses to drugs enables computational approaches to drug repositioning directly based on measured molecular effects. Results: We introduce a novel computational methodology for rational drug repositioning, which exploits the transcriptional responses following treatment with small molecule. Specifically, given a therapeutic target gene, a prioritisation of potential effective drugs is obtained by assessing their impact on the transcription of genes in the pathway(s) including the target...
December 11, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29236866/thiol-disulfide-status-regulates-the-activity-of-thiol-containing-kinases-related-to-energy-homeostasis-in-rat-kidney
#16
Virginia C Rech, Nathana J Mezzomo, Genaro A Athaydes, Luciane R Feksa, Vandré C Figueiredo, Adriana Kessler, Itiane D DE Franceschi, Clovis M D Wannmacher
Considering that thiol-containing enzymes like kinases are critical for several metabolic pathways and energy homeostasis, we investigated the effects of cystine dimethyl ester and/or cysteamine administration on kinases crucial for energy metabolism in the kidney of Wistar rats. Animals were injected twice a day with 1.6 µmol/g body weight cystine dimethyl ester and/or 0.26 µmol/g body weight cysteamine from the 16th to the 20th postpartum day and euthanized after 12 hours. Pyruvate kinase, adenylate kinase, creatine kinase activities and thiol/disulfide ratio were determined...
December 7, 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29236390/serum-glycomarkers-of-endoplasmic-reticulum-and-lysosomal-endosomal-system-stress-in-human-healthy-aging-and-diseases
#17
I U Pismenetskaya, T D Butters
To verify the idea that extracellular free oligosaccharides might be able to reflect the functional status of the endoplasmic reticulum (ER) and lysosomal-endosomal system, HPLC-profiles of serum-derived free oligosaccharides (FOS) in human healthy aging, acute myeloproliferative neoplasms, and cardiovascular pathologies were compared with intracellular glycans. After plasma deproteinization and FOS purification the oligosaccharides were labelled with anthranilic acid, separated into the neutral and charged with QAE Sephadex (Q25-120) chromatography and analysed using high-performance liquid chromatography (HPLC)...
January 2017: Ukrainian Biochemical Journal
https://www.readbyqxmd.com/read/29235891/lipid-biomarkers-for-the-peroxisomal-and-lysosomal-disorders-their-formation-metabolism-and-measurement
#18
Ryuichi Mashima, Masamitsu Maekawa
Lipid biomarkers play important roles in the diagnosis of and monitoring of treatment in peroxisomal disorders and lysosomal storage disorders. Today, a variety of lipids, including very long chain fatty acids, glycolipids, bile acids and the oxidation products of cholesterol, have been considered as biomarkers for these disorders. In this brief review, the authors summarized the recent advances regarding these lipid biomarkers in terms of their formation, metabolism and measurement in these disorders. An understanding of these biomarkers will offer a key to the development of novel diagnoses and help create more effective therapies in the future...
December 13, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/29234937/-lysosomal-acid-lipase-deficiency-lal-d-diagnostic-and-therapeutic-options-in-an-underdiagnosed-disease
#19
REVIEW
S Synoracki, S Kathemann, K W Schmid, H Jastrow, H A Baba
BACKGROUND AND CLINICAL SETTING: Lysosomal acid lipase deficiency is an autosomal recessive storage disease caused by mutations in the LIPA gene. The accumulation of cholesteryl esters and triglycerides in hepatocytes lead to hepatomegaly with progressive fibrosis and liver cirrhosis. Characteristically, patients have a hepatomegaly combined with high serum levels of cholesterol, LDL-cholesterol and in some cases triglyceride, whereas HDL-cholesterol is decreased. Histologically, hepatocytes show a microvesicular steatosis with typically ballooned Kupffer cells...
December 12, 2017: Der Pathologe
https://www.readbyqxmd.com/read/29234429/effects-of-jiawei-shaoyao-gancao-decoction-and-its-drug-containing-serum-on-proliferation-apoptosis-and-ultrastructure-of-human-adenomyosis-foci-cells
#20
Yu-Yan Zeng, Kun-Yin Li
Objective: The present study aimed to investigate the effects of Jiawei Shaoyao-Gancao Decoction (JSGD) and its drug-containing serum (CDS) on the proliferation, apoptosis, and ultrastructure of human adenomyosis foci cells. Methods: Primary cultures of human adenomyosis foci cells were prepared from hard uterine lesions of adenomyosis patients. The cells were treated with JSGD (10 and 20 mg/ml), CDS, and mifepristone (MIF) for 24 or 48 h. Cell proliferation was detected using CCK-8 assay, cell apoptosis was measured by flow cytometry, and the cell ultrastructure was observed by transmission electron microscopy (TEM)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
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