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https://www.readbyqxmd.com/read/28646542/reconstitution-of-low-density-lipoproteins-with-fatty-acids-for-the-targeted-delivery-of-drugs-into-cancer-cells
#1
Chunlei Zhu, Pallab Pradhan, Da Huo, Jiajia Xue, Song Shen, Krishnendu Roy, Younan Xia
Low-density lipoproteins (LDLs) represent a novel class of nanocarriers for the targeted delivery of therapeutics into aberrant cells that overexpress the LDL receptor. Here we report a facile procedure for reconstituting the hydrophobic core of LDLs with a binary fatty acid mixture. Facilitated by the tumor targeting capability of the apolipoprotein, the reconstituted, drug-loaded LDLs can effectively target cancer cells that overexpress the LDL receptor while showing minor adverse impact on normal fibroblasts...
June 24, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28646478/newborn-screening-for-fabry-disease-in-the-north-west-of-spain
#2
Cristobal Colon, Saida Ortolano, Cristina Melcon-Crespo, Jose V Alvarez, Olalla E Lopez-Suarez, Maria L Couce, José R Fernández-Lorenzo
Fabry disease is an X-linked lysosomal storage disorder caused by the impairment of α-galactosidase A. Enzyme replacement therapy is available to treat patients, who often experience delayed diagnosis. A newborn screening for Fabry disease was performed to study the prevalence of the pathology and to evaluate the possibility to implement the test in systematic screenings. We collected 14,600 dried blood spot samples (7575 males and 7025 females) and carried out a diagnostic study by fluorometric measurement of α-galactosidase A enzymatic activity and GLA gene sequencing...
June 23, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28646367/ifn%C3%AE-producing-cd4-t-lymphocytes-the-double-edged-swords-in-tuberculosis
#3
Pawan Kumar
IFNγ-producing CD4(+) T cells (IFNγ(+)CD4(+) T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ(+)CD4(+) T cells in TB pathogenesis. High frequency of IFNγ(+)CD4(+) T cells is the most invariable feature of the active disease...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28646090/cellular-functions-of-wasp-family-proteins-at-a-glance
#4
REVIEW
Olga Alekhina, Ezra Burstein, Daniel D Billadeau
Proteins of the Wiskott-Aldrich syndrome protein (WASP) family function as nucleation-promoting factors for the ubiquitously expressed Arp2/3 complex, which drives the generation of branched actin filaments. Arp2/3-generated actin regulates diverse cellular processes, including the formation of lamellipodia and filopodia, endocytosis and/or phagocytosis at the plasma membrane, and the generation of cargo-laden vesicles from organelles including the Golgi, endoplasmic reticulum (ER) and the endo-lysosomal network...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28645573/evidence-that-fetal-death-is-associated-with-placental-aging
#5
Kaushik Maiti, Zakia Sultana, Robert John Aitken, Jonathan Morris, Felicity Park, Bronwyn Andrew, Simon C Riley, Roger Smith
BACKGROUND: The risk of unexplained fetal death or stillbirth increases late in pregnancy suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA and lipids. We hypothesized that placentas at more than 41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. OBJECTIVE: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging...
June 20, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28644509/comparative-transcriptomic-analysis-of-two-important-life-stages-of-angiostrongylus-cantonensis-fifth-stage-larvae-and-female-adults
#6
Liang Yu, Binbin Cao, Ying Long, Meks Tukayo, Chonglv Feng, Wenzhen Fang, Damin Luo
The mechanisms involved in the fast growth of Angiostrongylus cantonensis from fifth-stage larvae (L5) to female adults and how L5 breaks through the blood-brain barrier in a permissive host remain unclear. In this work, we compared the transcriptomes of these two life stages to identify the main factors involved in the rapid growth and transition to adulthood. RNA samples from the two stages were sequenced and assembled de novo. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of 1,346 differentially expressed genes between L5 and female adults was then undertaken...
April 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28644464/a-synthetic-ion-transporter-that-disrupts-autophagy-and-induces-apoptosis-by-perturbing-cellular-chloride-concentrations
#7
Nathalie Busschaert, Seong-Hyun Park, Kyung-Hwa Baek, Yoon Pyo Choi, Jinhong Park, Ethan N W Howe, Jennifer R Hiscock, Louise E Karagiannidis, Igor Marques, Vítor Félix, Wan Namkung, Jonathan L Sessler, Philip A Gale, Injae Shin
Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol...
July 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28643291/-more-than-expectorant-new-scientific-data-on-ambroxol-in-the-context-of-the-treatment-of-bronchopulmonary-diseases
#8
Manuel Plomer, Justus de Zeeuw
BACKGROUND: Ambroxol has been established for decades in the treatment of acute and chronic respiratory diseases. In 2015, the European Medicines Agency reassessed the clinical benefit-risk ratio of the drug. OBJECTIVE: What new scientific data on ambroxol, which are relevant to the treatment of bronchopulmonary diseases, are available? METHOD: The review is based on a systematic literature research in medline with the search term "ambroxol" during the publication period 2006-2015...
June 2017: MMW Fortschritte der Medizin
https://www.readbyqxmd.com/read/28643086/gallic-and-ellagic-acids-two-natural-immunomodulator-compounds-solve-infection-of-macrophages-by-leishmania-major
#9
Michel Muálem de Moraes Alves, Lucas Moreira Brito, Adriana Cunha Souza, Bárbara Cristina Silva Holanda Queiroz, Thaynara Parente de Carvalho, Joilson Ferreira Batista, Jéssica Sara de Sousa Macêdo Oliveira, Ivete Lopes de Mendonça, Silvéria Regina de Sousa Lira, Mariana Helena Chaves, Juan Carlos Ramos Gonçalves, Sabrina Maria Portela Carneiro, Daniel Dias Rufino Arcanjo, Fernando Aécio de Amorim Carvalho
Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities...
June 22, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28642633/proteases-revisited-roles-and-therapeutic-implications-in-fibrosis
#10
REVIEW
Jakub Kryczka, Joanna Boncela
Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., proteolysis of nonactive zymogens), decomposition of cell-cell junctions, release of sequestered growth factors (TGF-β and VEGF), activation of signal proteins and receptors, degradation of inflammatory inhibitors or inflammation-related proteins, and changes in cell mechanosensing and motility...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28642584/molecular-switching-system-using-glycosylphosphatidylinositol-to-select-cells-highly-expressing-recombinant-proteins
#11
Emmanuel Matabaro, Zeng'an He, Yi-Shi Liu, Hui-Jie Zhang, Xiao-Dong Gao, Morihisa Fujita
Although many pharmaceutical proteins are produced in mammalian cells, there remains a challenge to select cell lines that express recombinant proteins with high productivity. Since most biopharmaceutical proteins are secreted by cells into the medium, it is difficult to select cell lines that produce large amounts of the target protein. To address this issue, a new protein expression system using the glycosylphosphatidylinositol (GPI)-anchor was developed. PGAP2 is involved in processing GPI-anchored proteins (GPI-APs) during transport...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642463/acute-loss-of-the-hepatic-endo-lysosomal-system-in-vivo-causes-compensatory-changes-in-iron-homeostasis
#12
Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial, Martina U Muckenthaler
Liver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641977/a-novel-fluorescent-probe-reveals-starvation-controls-the-commitment-of-amyloid-precursor-protein-to-the-lysosome
#13
Leanne K Hein, Pirjo M Apaja, Kathryn Hattersley, Randall H Grose, Jianling Xie, Christopher G Proud, Timothy J Sargeant
Alzheimer's disease is the most important cause of dementia but there is no therapy that has been demonstrated to stop or slow disease progression. Amyloid precursor protein (APP) is the source of amyloid-β (Aβ), which aggregates in Alzheimer's disease to form toxic oligomeric species. The endo-lysosomal system can clear APP and Aβ from the cell if these molecular species are trafficked through to the lysosome. Currently, there are no easy methods available for the analysis of lysosomal APP trafficking. We therefore generated a fusion protein (tandem-fluorescent, or tf-APP) that allows detection of changes in APP trafficking using accessible techniques such as flow cytometry...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641519/neural-stem-cells-and-human-induced-pluripotent-stem-cells-to-model-rare-cns-diseases
#14
Lidia De Filippis, Cristina Zalfa, Daniela Ferrari
Despite the great effort spent over the last decades to unravel the pathological mechanisms underpinning the development of central nervous system disorders, most of them remain still unclear. In particular, the study of rare brain diseases is hurdled by the lack of post-mortem samples and of reliable epidemiological studies, thus the setting of in vitro modeling systems appears essential to dissect the puzzle of genetic and environmental alterations affecting neural cells viability and functionality The isolation and expansion in vitro of embryonic (ESC) and fetal neural stem cells (NSC) from human tissue has efficiently allowed to model several neurological diseases "in a dish" and has also provided a novel platform to test potential therapeutic strategies in a pre-clinical setting...
June 15, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28641163/6-shogaol-induces-autophagic-cell-death-then-triggered-apoptosis-in-colorectal-adenocarcinoma-ht-29-cells
#15
Ting-Yi Li, Been-Huang Chiang
6-shogaol is a phytochemical of dietary ginger, we found that 6-shogaol could induced both autophagic and apoptotic death in human colon adenocarcinoma (HT-29) cells. Results of this study showed that 6-shogal induced cell cycle arrest, autophagy, and apoptosis in HT-29 cells in a time sequence. After 6h, 6-shogal induced apparent G2/M arrest, then the HT-29 cells formed numerous autophagosomes in each phase of the cell cycle. After 18h, increases in acidic vesicles and LAMP-1 (Lysosome-associated membrane proteins 1) showed that 6-shogaol had caused autophagic cell death...
June 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28640995/colloidal-gold-nanoparticles-induce-changes-in-cellular-and-subcellular-morphology
#16
Xiaowei Ma, Raimo Hartmann, Dorleta Jimenez de Aberasturi, Fang Yang, Stefaan J H Soenen, Bella B Manshian, Jonas Franz, Daniel Valdeperez, Beatriz Pelaz, Neus Feliu, Norbert Hampp, Christoph Riethmüller, Henning Vieker, Natalie Frese, Armin Gölzhäuser, Michael Simonich, Robert L Tanguay, Xing-Jie Liang, Wolfgang J Parak
Exposure of cells to colloidal nanoparticles (NPs) can have concentration-dependent harmful effects. Mostly, such effects are monitored with biochemical assays or probes from molecular biology, i.e. viability assays, gene expression profiles, etc., neglecting that the presence of NPs can also drastically affect cellular morphology. In the case of polymer-coated Au NPs we demonstrate that upon NP internalization, cells undergo lysosomal swelling, alterations in mitochondrial morphology, disturbances in actin and tubulin cytoskeleton and associated signaling, and reduction of focal adhesion contact area and number of filopodia...
June 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28640985/the-interaction-between-progranulin-and-prosaposin-is-mediated-by-granulins-and-the-linker-region-between-saposin-b-and-c
#17
Xiaolai Zhou, Peter M Sullivan, Lirong Sun, Fenghua Hu
The frontotemporal lobar degeneration (FTLD) protein progranulin (PGRN) is essential for proper lysosomal function. PGRN localizes in the lysosomal compartment within the cell. Prosaposin (PSAP), the precursor of lysosomal saposin activators (saposin A, B, C, D), physically interacts with PGRN. Previously we have shown that PGRN and PSAP facilitate each other's lysosomal trafficking. Here we report that the interaction between PSAP and PGRN requires the linker region of saposin B and C (BC linker). PSAP protein with the BC linker mutated fails to interact with PGRN and target PGRN to lysosomes in the biosynthetic and endocytic pathways...
June 22, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28640947/clinico-molecular-analysis-of-eleven-patients-with-hermansky-pudlak-type-5-syndrome-a-mild-form-of-hps
#18
Vincent Michaud, Eulalie Lasseaux, Claudio Plaisant, Alain Verloes, Yaumara Perdomo-Trujillo, Christian Hamel, Nursel H Elcioglu, Bart Leroy, Josseline Kaplan, Pierre-Simon Jouk, Didier Lacombe, Patricia Fergelot, Fanny Morice-Picard, Benoit Arveiler
Hermansky-Pudlak syndrome (HPS), first described in 1959, is a rare form of syndromic oculocutaneous albinism associated with bleeding diathesis and in some cases pulmonary fibrosis and granulomatous colitis. All 10 HPS types are caused by defects in vesicle trafficking of lysosomes-related organelles (LRO) proteins. The HPS5 protein associates with HPS3 and HPS6 to form the Biogenesis of Lysosome-related Organelles Complex-2 (BLOC-2). Here we report the clinical and genetic data of 11 HPS-5 patients analyzed in our laboratory...
June 22, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28639285/porphyrin-modified-trastuzumab-improves-efficacy-of-her2-targeted-photodynamic-therapy-of-gastric-cancer
#19
Barbara Korsak, Gabriela M Almeida, Sara Rocha, Carla Pereira, Nuno Mendes, Hugo Osório, Patrícia M R Pereira, João M M Rodrigues, Rudolf J Schneider, Bruno Sarmento, João P C Tomé, Carla Oliveira
Gastric cancer (GC) is the 3(rd) deadliest cancer worldwide, due to limited treatment options and late diagnosis. Human epidermal growth factor receptor-2 (HER2) is overexpressed in ∼20% of GC cases and anti-HER2 antibody trastuzumab in combination with conventional chemotherapy, is recognized as standard therapy for HER2-positive metastatic GC. This strategy improves GC patients' survival by 2-3 months, however its optimal results in breast cancer indicate that GC survival may be improved. A new photoimmunoconjugate was developed by conjugating a porphyrin with trastuzumab (Trast:Porph) for targeted photodynamic therapy in HER2-positive GC...
June 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28638925/-autophagy-and-hypoxic-ischemic-brain-injuries
#20
Yong-Qiang Li, Su Fu, Lai Wang, Bin Liu, Zhen-Yu Shi, Jin-Bo Deng
Autophagy is a highly evolutionarily conserved physiological mechanism of organism, including several stages such as autophagosomes formation, the fusion of lysosomes and autophagosomes, and autophagosomes degradation. In physiological conditions, autophagy is responsible for clearing the spoiled organelles and long-lived proteins to maintain the homeostasis of cells and organism. Meanwhile, autophagy is also involved in the formation and development of diseases, but the mechanism has not been confirmed yet...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
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