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https://www.readbyqxmd.com/read/28326166/trail-delivery-by-msc-derived-extracellular-vesicles-is-an-effective-anticancer-therapy
#1
ZhengQiang Yuan, Krishna K Kolluri, Kate H C Gowers, Sam M Janes
Extracellular vesicles (EVs) are lipid membrane-enclosed nanoparticles released by cells. They mediate intercellular communication by transferring biological molecules and therefore have potential as innovative drug delivery vehicles. TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis of cancer cells. Unfortunately, the clinical application of recombinant rTRAIL has been hampered by its low bioavailability and resistance of cancer cells. EV-mediated TRAIL delivery may circumvent these problems...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28323918/elucidating-the-role-of-the-desmosome-protein-p53-apoptosis-effector-related-to-pmp-22-perp-in-growth-hormone-tumors
#2
Katja Kiseljak-Vassiliades, Taylor S Mills, Yu Zhang, Mei Xu, Kevin O Lillehei, B K Kleinschmidt-DeMasters, Margaret E Wierman
Purpose: Densely granulated (DG) and sparsely granulated (SG) growth hormone (GH) pituitary adenomas differ in biological behavior which may be correlated with their known differences in cytoplasmic keratin distribution and E-cadherin expression. We desired to explore candidate genes which might further explain this behavior. Methods: Exon expression microarray was performed on 21 GH tumors (10 SG and 11 DG) and 20 normal control pituitaries from autopsy. Results: Bioinformatic analyses confirmed a differential molecular signature between normal pituitary and GH tumors as well as between the GH tumor subtypes...
February 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28314260/induction-of-apoptosis-in-human-oral-keratinocyte-by-doxorubicin
#3
Hiroshi Sakagami, Noriyuki Okudaira, Yoshiko Masuda, Osamu Amano, Satoshi Yokose, Yumiko Kanda, Madoka Suguro, Takenori Natori, Hiroshi Oizumi, Takaaki Oizumi
BACKGROUND/AIM: We have previously reported that doxorubicin (DXR) showed much higher cytotoxicity against human oral squamous cell carcinoma cell lines compared to normal human mesenchymal normal oral cells (gingival fibroblast, periodontal ligament fibroblast, pulp cell), yielding high tumor-specificity. However, we unexpectedly found that doxorubicin showed potent cytotoxicity against human normal oral keratinocytes and primary gingival epithelial cells. In the present study, we investigated the reproducibility, underlining mechanisms and generality of this unexpected finding...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314211/the-role-of-kupffer-cells-in-hepatic-diseases
#4
REVIEW
Peizhi Li, Kun He, Jinzheng Li, Zuojin Liu, Jianping Gong
Kupffer cells (KCs) constitute 80-90% of the tissue macrophages present in the body. Essential to innate and adaptive immunity, KCs are responsible for the swift containment and clearance of exogenous particulates and immunoreactive materials which are perceived as foreign and harmful to the body. Similar to other macrophages, KCs also sense endogenous molecular signals that may result from perturbed homeostasis of the host. KCs have been implicated in host defense and the pathogenesis of various hepatic diseases, including endotoxin tolerance, liver transplantation, nonalcoholic fatty liver disease, and alcoholic liver disease...
March 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28291403/a-rat-model-of-chronic-syringomyelia-induced-by-epidural-compression-of-the-lumbar-spinal-cord
#5
Ji Yeoun Lee, Shin Won Kim, Saet Pyoul Kim, Hyeonjin Kim, Jung-Eun Cheon, Seung-Ki Kim, Sun Ha Paek, Dachling Pang, Kyu-Chang Wang
OBJECTIVE There has been no established animal model of syringomyelia associated with lumbosacral spinal lipoma. The research on the pathophysiology of syringomyelia has been focused on Chiari malformation, trauma, and inflammation. To understand the pathophysiology of syringomyelia associated with occult spinal dysraphism, a novel animal model of syringomyelia induced by chronic mechanical compression of the lumbar spinal cord was created. METHODS The model was made by epidural injection of highly concentrated paste-like kaolin solution through windows created by partial laminectomy of L-1 and L-5 vertebrae...
February 17, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/28286420/hlbt-100-a-highly-potent-anti-cancer-flavanone-from-tillandsia-recurvata-l-l
#6
Henry I C Lowe, Ngeh J Toyang, Charah T Watson, Kenneth N Ayeah, Joseph Bryant
BACKGROUND: The incidence and mortalities from cancers remain on the rise worldwide. Despite significant efforts to discover and develop novel anticancer agents, many cancers remain in the unmet need category. As such, efforts to discover and develop new and more effective and less toxic agents against cancer remain a top global priority. Our drug discovery approach is natural products based with a focus on plants. Tillandsia recurvata (L.) L. is one of the plants selected by our research team for further studies based on previous bioactivity findings on the anticancer activity of this plant...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28281516/-features-of-a-necrotic-and-inflammatory-process-in-different-forms-of-nonalcoholic-fatty-liver-disease
#7
I V Kurbatova, O P Dudanova
AIM: To identify the features of development of a necrotic and inflammatory process in different forms of nonalcoholic fatty liver disease (NAFLD), by comparatively analyzing a full set of clinical and laboratory parameters, including the cytokine status and the expression level of enzyme genes controlling the apoptosis of peripheral leukocytes. SUBJECTS AND METHODS: 86 patients with NAFLD, including 8 (9.3%) with hepatic steatosis (HS), 70 (81.4%) with nonalcoholic steatohepatitis (NASH), 40, 19, and 11 with mild, moderate, and high disease activity, respectively, and 8 (9...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28280602/impact-of-caspase-1-11-3-7-or-il-1%C3%AE-il-18-deficiency-on-rabies-virus-induced-macrophage-cell-death-and-onset-of-disease
#8
E Kip, F Nazé, V Suin, T Vanden Berghe, A Francart, S Lamoral, P Vandenabeele, R Beyaert, S Van Gucht, M Kalai
Rabies virus is a highly neurovirulent RNA virus, which causes about 59000 deaths in humans each year. Previously, we described macrophage cytotoxicity upon infection with rabies virus. Here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies virus: Challenge Virus Standard strain-11 (CVS-11) is highly neurotropic and lethal for mice, while the attenuated Evelyn-Rotnycki-Abelseth (ERA) strain has a broader cell tropism, is non-lethal and has been used as an oral vaccine for animals...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28275791/-knockdown-of-grb7-inhibits-growth-of-oral-squamous-cell-carcinoma-cell-proliferation-and-promoted-apoptosis-through-erk-foxm1-pathway
#9
Bing-Yao Liu, Gang Cao, Zhen Dong, Wei Chen, Jin-Ke Xu, Sen-Lin Zhang, Zhi-Qiang Weng
PURPOSE: To investigate the effect of growth factor receptor-bound 7 (Grb7) on oral squamous cell carcinoma growth and tumor xenografts. METHODS: Cal27 and hNOK cells were cultivated, real-time PCR and Western blotting were used to detect the expression of Grb7 in hNOK and Cal27. Cal27 was transfected with Grb7 siRNA for 48 h, cell proliferation was assayed using MTT. Flow cytometry was used to determine the cell cycle and apoptosis. Western blot was used to evaluate the expression of caspase3, Bax, bcl-2, Cyclin D1, Rb, E2F1, ERK and FOXM1...
December 2016: Shanghai Kou Qiang Yi Xue, Shanghai Journal of Stomatology
https://www.readbyqxmd.com/read/28266268/p2x7-receptor-orchestrates-multiple-signalling-pathways-triggering-inflammation-autophagy-and-metabolic-trophic-responses
#10
Elisa Orioli, Elena De Marchi, Anna Lisa Giuliani, Elena Adinolfi
P2X7 receptor is an ion channel activated by extracellular adenosine trisphosphate (eATP) that attracted increasing attention for its role in immune reactions, neurobiology and oncology. As receptor for an extracellular ligand, P2X7 activates a series of intracellular signalling pathways mainly via alterations of the ion permeability, but also through formation of a large unselective pore and direct interaction with other proteins. Here we wish to give an overview on the main biochemical paths initiated by P2X7 activation by revising recent and established literature on P2X7-triggered signalling cascades leading to cell death, inflammatory and immune response activation, proliferation and metabolism modulation...
March 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28259972/inhibitory-effects-of-vitamin-e-on-osteocyte-apoptosis-and-dna-oxidative-damage-in-bone-marrow-hemopoietic-cells-at-early-stage-of-steroid-induced-femoral-head-necrosis
#11
Yan-Bo Jia, Dian-Ming Jiang, Yi-Zhong Ren, Zi-Hong Liang, Zhen-Qun Zhao, Yu-Xin Wang
Apoptosis and DNA oxidative damage serve significant roles in the pathogenesis of steroid‑induced femoral head necrosis. Vitamin E demonstrates anti‑apoptotic and anti‑oxidant properties. Therefore, the present study investigated the effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at an early stage of steroid‑induced femoral head osteonecrosis. Japanese white rabbits were randomly divided into three groups (steroid, vitamin E‑treated, and control groups), each comprising 12 rabbits...
February 2, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28253574/-reverse-of-the-resistance-to-paclitaxel-of-the-heparin-binding-epidermal-growth-factor-like-growth-factor-inhibitor-in-ovarian-cancer
#12
X H Tang, M S Lu, S Deng, M Li
Objective: To investigate the effect and mechanism of CRM197, the heparin binding-epidermal growth factor-like growth factor (HB-EGF) inhibitor, on the reverse of the resistance of ovarian cancer to paclitaxel. Methods: (1)The effect of CRM197 on the 50% inhibitory concentrations (IC(50)) of human ovarian carcinoma cell line A2780 and paclitaxel-resistant ovarian carcinoma cell line A2780/Taxol was tested by methyl thiazolyl tetrazolium (MTT) assay. Western blot was used to detect the effect of CRM197 on the expression of HB-EGF, epidermal growth factor receptor (EGFR) and plasma membrane glycoprotein (P-gp) protein in A2780 and A2780/Taxol cells...
February 25, 2017: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/28246455/molecular-markers-for-resistance-against-infectious-diseases-of-economic-importance
#13
REVIEW
B M Prajapati, J P Gupta, D P Pandey, G A Parmar, J D Chaudhari
Huge livestock population of India is under threat by a large number of endemic infectious (bacterial, viral, and parasitic) diseases. These diseases are associated with high rates of morbidity and mortality, particularly in exotic and crossbred cattle. Beside morbidity and mortality, economic losses by these diseases occur through reduced fertility, production losses, etc. Some of the major infectious diseases which have great economic impact on Indian dairy industries are tuberculosis (TB), Johne's disease (JD), mastitis, tick and tick-borne diseases (TTBDs), foot and mouth disease, etc...
January 2017: Veterinary World
https://www.readbyqxmd.com/read/28238093/role-of-hif-1%C3%AE-and-caspase-3-in-cystogenesis-of-odontogenic-cysts-and-tumors
#14
Natacha M M da Costa, Adriane S de Siqueira, André L R Ribeiro, Maria S da Silva Kataoka, Ruy G Jaeger, Sérgio M de Alves-Júnior, Andrew M Smith, João de Jesus Viana Pinheiro
OBJECTIVES: Odontogenic cysts and tumors are the most relevant lesions that affect the gnathic bones. These lesions have in common the formation of cystic areas and this common feature may suggest involvement of similar mechanisms. The hypoxia inducible factor 1 alpha (HIF-1α), a responsive protein to hypoxia and caspase-3, an irreversible apoptosis marker, may contribute to cyst formation. Thus, this study aimed to investigate the immunoexpression of these proteins in odontogenic cysts and tumors...
February 25, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28237528/identification-of-potential-therapeutic-target-genes-key-mirnas-and-mechanisms-in-oral-lichen-planus-by-bioinformatics-analysis
#15
Cuihua Gong, Shangtong Sun, Bing Liu, Jing Wang, Xiaodong Chen
The study aimed to identify the potential target genes and key miRNAs as well as to explore the underlying mechanisms in the pathogenesis of oral lichen planus (OLP) by bioinformatics analysis. The microarray data of GSE38617 were downloaded from Gene Expression Omnibus (GEO) database. A total of 7 OLP and 7 normal samples were used to identify the differentially expressed genes (DEGs) and miRNAs. The DEGs were then performed functional enrichment analyses. Furthermore, DEG-miRNA network and miRNA-function network were constructed by Cytoscape software...
February 12, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28222398/isolation-of-a-new-resorcinolic-lipid-from-mangifera-zeylanica-hook-f-bark-and-its-cytotoxic-and-apoptotic-potential
#16
Meran Keshawa Ediriweera, Kamani Hemamala Tennekoon, Sameera Ranganath Samarakoon, Achyut Adhikari, Ira Thabrew, E Dilip de Silva
Mangifera zeylanica is a plant endemic to Sri Lanka and its bark has been used in traditional medicine to treat some cancers. This study was aimed to isolate potentially cytotoxic compound/s from the hexane extract of the bark of M. zeylanica by bio-activity guided fractionation. The structure of the isolated compound (1) was elucidated using (1)H, (13)C NMR and mass spectrometric techniques. Compound 1 was identified as a new resorcinolic lipid (5-((8Z, 11Z, 14Z)-hexatriaconta-8, 11, 14-trienyl) benzene-1,3-diol)...
February 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28215509/triphenylphosphonium-modified-poly-ethylene-glycol-poly-%C3%AE%C2%B5-caprolactone-micelles-for-mitochondria-targeted-gambogic-acid-delivery
#17
Yingqi Xu, Shengpeng Wang, Hon Fai Chan, Yuling Liu, Hui Li, Chengwei He, Zeyong Li, Meiwan Chen
Mitochondria are important targets for the intracellular delivery of drugs and DNA. For mitochondria-targeted delivery, a mitochondriotropic molecule, triphenylphosphonium (TPP), was applied to the synthesis of amphiphilic TPP-poly(ethylene glycol)-poly(ε-caprolactone) (TPP-PEG-PCL) polymers. The TPP-PEG-PCL polymer was used to prepare micelles using a solvent evaporation method for the delivery of gambogic acid (GA) (GA-TPP). The micelles were obtained with a favorable particle size of 150.07±11.71nm and an encapsulation efficiency of 80...
February 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28214863/stimulation-of-erythrocyte-cell-membrane-scrambling-by-c-reactive-protein
#18
Majed Abed, Christian Thiel, Syeda T Towhid, Kousi Alzoubi, Sabina Honisch, Florian Lang, Alfred Königsrainer
BACKGROUND: Eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine-translocation, is triggered by fever and inflammation. Signaling includes increased cytosolic Ca2+-activity ([Ca2+]i), caspase activation, and ceramide. Inflammation is associated with increased plasma concentration of C-reactive protein (CRP). The present study explored whether CRP triggers eryptosis. METHODS: Phosphatidylserine abundance at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide abundance and caspase-3-activity utilizing FITC-conjugated antibodies...
February 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28197335/caspase-8-not-so-silently-deadly
#19
REVIEW
Rebecca Feltham, James E Vince, Kate E Lawlor
Apoptosis is a caspase-dependent programmed form of cell death, which is commonly believed to be an immunologically silent process, required for mammalian development and maintenance of cellular homoeostasis. In contrast, lytic forms of cell death, such as RIPK3- and MLKL-driven necroptosis, and caspase-1/11-dependent pyroptosis, are postulated to be inflammatory via the release of damage associated molecular patterns (DAMPs). Recently, the function of apoptotic caspase-8 has been extended to the negative regulation of necroptosis, the cleavage of inflammatory interleukin-1β (IL-1β) to its mature bioactive form, either directly or via the NLRP3 inflammasome, and the regulation of cytokine transcriptional responses...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28197319/structure-based-design-of-non-natural-peptidic-macrocyclic-mcl-1-inhibitors
#20
Jeffrey W Johannes, Stephanie Bates, Carl Beigie, Matthew A Belmonte, John Breen, Shenggen Cao, Paolo A Centrella, Matthew A Clark, John W Cuozzo, Christoph E Dumelin, Andrew D Ferguson, Sevan Habeshian, David Hargreaves, Camil Joubran, Steven Kazmirski, Anthony D Keefe, Michelle L Lamb, Haiye Lan, Yunxia Li, Hao Ma, Scott Mlynarski, Martin J Packer, Philip B Rawlins, Daniel W Robbins, Haidong Shen, Eric A Sigel, Holly H Soutter, Nancy Su, Dawn M Troast, Haiyun Wang, Kate F Wickson, Chengyan Wu, Ying Zhang, Qiuying Zhao, Xiaolan Zheng, Alexander W Hird
Mcl-1 is a pro-apoptotic BH3 protein family member similar to Bcl-2 and Bcl-xL. Overexpression of Mcl-1 is often seen in various tumors and allows cancer cells to evade apoptosis. Here we report the discovery and optimization of a series of non-natural peptide Mcl-1 inhibitors. Screening of DNA-encoded libraries resulted in hit compound 1, a 1.5 μM Mcl-1 inhibitor. A subsequent crystal structure demonstrated that compound 1 bound to Mcl-1 in a β-turn conformation, such that the two ends of the peptide were close together...
February 9, 2017: ACS Medicinal Chemistry Letters
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