CRISPR-Cas9 delivery to hard-to-transfect cells via membrane deformation.
AuthorsHan X, Liu Z, Jo MC, Zhang K, Li Y, Zeng Z, Li N, Zu Y, Qin L,
Journal
PubMed ID26601238
'The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) nuclease system represents an efficient tool for genome editing and gene function analysis. It consists of two components: single-guide RNA (sgRNA) and the enzyme Cas9. Typical sgRNA and Cas9 intracellular delivery techniques are limited by their reliance on cell type and ... More
Clinically applicable magnetic-labeling of natural killer cells for MRI of transcatheter delivery to liver tumors: preclinical validation for clinical translation.
AuthorsLi K, Gordon AC, Zheng L, Li W, Guo Y, Sun J, Zhang G, Han G, Larson AC, Zhang Z,
Journal
PubMed ID26080698
To test the hypothesis that MRI can monitor intraportal vein (IPV) transcatheter delivery of clinically applicable heparin-protamine-ferumoxytol (HPF) nanocomplex-labeled natural killer (NK) cells to liver tumor. Liver tumor rat models underwent catheterization for IPV infusion of HPF-labeled NK cells (NK-92MI cell line). MRI measurements within tumor and adjacent liver tissues ... More
Selective Induction of Apoptosis by Azadarichta indica Leaf Extract by Targeting Oxidative Vulnerabilities in Human Cancer Cells.
AuthorsRoma A, Ovadje P, Steckle M, Nicoletti L, Saleem A, Pandey S
Journal
PubMed ID26626256
Natural products have been a great source of medications used in conventional medicines for the treatment of various diseases; more importantly, they have played a significant role in the development of anti-cancer drugs for a number of decades. The benefits to employing whole extracts of natural health products, rather than ... More
Tumor Microenvironment Remodeling by 4-Methylumbelliferone Boosts the Antitumor Effect of Combined Immunotherapy in Murine Colorectal Carcinoma.
AuthorsMalvicini M, Fiore E, Ghiaccio V, Piccioni F, Rizzo M, Olmedo Bonadeo L, García M, Rodríguez M, Bayo J, Peixoto E, Atorrasagasti C, Alaniz L, Aquino J, Matar P, Mazzolini G,
Journal
PubMed ID26105158
We have previously demonstrated that a low dose of cyclophosphamide (Cy) combined with gene therapy of interleukin-12 (AdIL-12) has a synergistic, although limited, antitumoral effect in mice with colorectal carcinoma. The main mechanism involved in the efficacy of Cy+AdIL-12 was the induction of a specific immune response mediated by cytotoxic ... More
Enrichment of circulating head and neck tumour cells using spiral microfluidic technology.
AuthorsKulasinghe A, Tran TH, Blick T, O'Byrne K, Thompson EW, Warkiani ME, Nelson C, Kenny L, Punyadeera C
JournalSci Rep
PubMed ID28198401
'Whilst locoregional control of head and neck cancers (HNCs) has improved over the last four decades, long-term survival has remained largely unchanged. A possible reason for this is that the rate of distant metastasis has not changed. Such disseminated disease is reflected in measurable levels of cancer cells in the ... More
Applicability of Automated Cell Counter with a Chlorophyll Detector in Routine Management of Microalgae.
AuthorsTakahashi T,
JournalSci Rep
PubMed ID29563559
'Microalgae have attracted attention for several industrial applications, but all such applications demand culture quality because of their sensitivity to environmental changes. Although simplicity, speed, and accuracy are important to assess algal cultures, researchers have expended vast amounts of labor to monitor algal health using hemocytometry. Along with its user ... More
Optimizing a serum-free/xeno-free culture medium for culturing and promoting the proliferation of human dental pulp stem cells.
AuthorsAbdel Moniem EM, El-Batran MM, Halawa AM, Gomaa DH, Eldeen GN, Aly RM,
JournalStem Cell Investig
PubMed ID31304181
'Dental pulp stem cells (DPSCs) hold great promise for utilization in tissue repair and regenerative medicine. Routinely, culture media used for culturing stem cells are supplemented with animal serum for promoting growth and successful maintenance of stem cells. However, there is a growing demand for optimizing a well-defined culture media ... More
In Vitro Self-Renewal Assays for Brain Tumor Stem Cells.
AuthorsSeyfrid M, Bobrowski D, Bakhshinyan D, Tatari N, Venugopal C, Singh SK,
JournalMethods Mol Biol
PubMed ID30324515
'Early development of human organisms relies on stem cells, a population of non-specialized cells that can divide symmetrically to give rise to two identical daughter cells, or divide asymmetrically to produce one identical daughter cell and another more specialized cell. The capacity to undergo cellular divisions while maintaining an undifferentiated ... More
Chemically Defined Neural Conversion of Human Pluripotent Stem Cells.
AuthorsChen Y, Tristan CA, Mallanna SK, Ormanoglu P, Titus S, Simeonov A, Singeç I,
JournalMethods Mol Biol
PubMed ID30656621
'Human pluripotent stem cells (hPSCs) are characterized by their ability to self-renew and differentiate into any cell type of the human body. To fully utilize the potential of hPSCs for translational research and clinical applications, it is critical to develop rigorous cell differentiation protocols under feeder-free conditions that are efficient, ... More
Expression of miR-21 and miR-138 in colon cancer and its effect on cell proliferation and prognosis.
AuthorsYou C, Jin L, Xu Q, Shen B, Jiao X, Huang X,
JournalOncol Lett
PubMed ID30675293
'Effect of miR-21 and miR-138 on the proliferation of colon cancer cells and their association with prognosis were investigated. Expression levels of miR-21 and miR-138 in colorectal cancer and normal adjacent tissues were compared. Differential expression of miR-21 and miR-138 in colon cancer tissues with different clinicopathological features were analyzed. ... More
A Multilayer Polymer-Film Inertial Microfluidic Device for High-Throughput Cell Concentration.
AuthorsXiang N, Zhang R, Han Y, Ni Z,
JournalAnal Chem
PubMed ID30920789
'We report here a novel multilayer polymer-film inertial microfluidic (MPIM) device with complex three-dimensional (3D) fluidic paths for realizing the massive parallelization of multiplexing functional channels. The proposed MPIM device is fabricated by simply stacking different polymer-film channel layers and adhesive layers. As a prototype demonstration, an MPIM device with ... More
Exploring the scope of new arylamino alcohol derivatives: Synthesis, antimalarial evaluation, toxicological studies, and target exploration.
AuthorsQuiliano M, Mendoza A, Fong KY, Pabón A, Goldfarb NE, Fabing I, Vettorazzi A, López de Cerain A, Dunn BM, Garavito G, Wright DW, Deharo E, Pérez-Silanes S, Aldana I, Galiano S
JournalInt J Parasitol Drugs Drug Resist
PubMed ID27718413
'Synthesis of new 1-aryl-3-substituted propanol derivatives followed by structure-activity relationship, in silico drug-likeness, cytotoxicity, genotoxicity, in silico metabolism, in silico pharmacophore modeling, and in vivo studies led to the identification of compounds 22 and 23 with significant in vitro antiplasmodial activity against drug sensitive (D6 IC50 = 0.19 µM) and multidrug resistant (FCR-3 IC50 = 0.40 µM and ... More
Two-Photon Microscopy Analysis of Gold Nanoparticle Uptake in 3D Cell Spheroids.
AuthorsRane TD, Armani AM
JournalPLoS One
PubMed ID27936027
'Nanomaterials can be synthesized from a wide range of material systems in numerous morphologies, creating an extremely diverse portfolio. As result of this tunability, these materials are emerging as a new class of nanotherapeutics and imaging agents. One particularly interesting nanomaterial is the gold nanoparticle. Due to its inherent biocompatibility ... More
Differences in Allelic Frequency and CDRH3 Region Limit the Engagement of HIV Env Immunogens by Putative VRC01 Neutralizing Antibody Precursors.
AuthorsYacoob C, Pancera M, Vigdorovich V, Oliver BG, Glenn JA, Feng J, Sather DN, McGuire AT, Stamatatos L
JournalCell Rep
PubMed ID27806295
'Elicitation of broadly neutralizing antibodies remains a long-standing goal of HIV vaccine research. Although such antibodies can arise during HIV-1 infection, gaps in our knowledge of their germline, pre-immune precursor forms, as well as on their interaction with viral Env, limit our ability to elicit them through vaccination. Studies of ... More
Dihydrotestosterone synthesis pathways from inactive androgen 5a-androstane-3ß,17ß-diol in prostate cancer cells: Inhibition of intratumoural 3ß-hydroxysteroid dehydrogenase activities by abiraterone.
AuthorsAndo T, Nishiyama T, Takizawa I, Ishizaki F, Miyashiro Y, Takeda K, Hara N, Tomita Y
JournalSci Rep
PubMed ID27561382
'Intratumoural dihydrotestosterone (DHT) synthesis could be an explanation for castration resistance in prostate cancer (PC). By using liquid chromatography-mass spectrometry, we evaluated the intratumoral DHT synthesis from 5a-androstane-3ß,17ß-diol (3ß-diol), which is inactive androgen metabolized from DHT. 3ß-diol had biochemical potential to be converted to DHT via three metabolic pathways and ... More
Rapalog resistance is associated with mesenchymal-type changes in Tsc2-null cells.
AuthorsValianou M, Filippidou N, Johnson DL, Vogel P, Zhang EY, Liu X, Lu Y, Yu JJ, Bissler JJ, Astrinidis A,
JournalSci Rep
PubMed ID30816188
'Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM) are caused by inactivating mutations in TSC1 or TSC2, leading to mTORC1 hyperactivation. The mTORC1 inhibitors rapamycin and analogs (rapalogs) are approved for treating of TSC and LAM. Due to their cytostatic and not cytocidal action, discontinuation of treatment leads to tumor regrowth ... More
Induction of Cell Death in Human A549 Cells Using 3-(Quinoxaline-3-yl) Prop-2-ynyl Methanosulphonate and 3-(Quinoxaline-3-yl) Prop-2-yn-1-ol.
'Despite major advancements in the development of various chemotherapeutic agents, treatment for lung cancer remains costly, ineffective, toxic to normal non-cancerous cells, and still hampered by a high level of remissions. A novel cohort of quinoxaline derivatives designed to possess a wide spectrum of biological activities was synthesized with promising ... More
Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial-Mesenchymal Transition: Enhanced Efficacy when Combined with Gemcitabine.
AuthorsWei R, Penso NEC, Hackman RM, Wang Y, Mackenzie GG,
JournalNutrients
PubMed ID31405071
'Most pancreatic cancers are usually diagnosed at an advanced stage when they have already metastasized. Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, has been shown to reduce pancreatic cancer growth, but its effect on metastasis remains elusive. This study evaluated the capacity of EGCG to inhibit pancreatic cancer ... More
Obesity alters oestrogen metabolism and contributes to pulmonary arterial hypertension.
AuthorsMair KM, Harvey KY, Henry AD, Hillyard DZ, Nilsen M, MacLean MR,
JournalEur Respir J
PubMed ID30923189
'Obesity is a common comorbidity for pulmonary arterial hypertension (PAH). Additionally, oestrogen and its metabolites are risk factors for the development of PAH. Visceral adipose tissue (VAT) is a major site of oestrogen production; however, the influence of obesity-induced changes in oestrogen synthesis and metabolism on the development of PAH ... More
Dietary Oligosaccharides Attenuate Stress-Induced Disruptions in Immune Reactivity and Microbial B-Vitamin Metabolism.
AuthorsAllen JM, Jaggers RM, Solden LM, Loman BR, Davies RH, Mackos AR, Ladaika CA, Berg BM, Chichlowski M, Bailey MT,
JournalFront Immunol
PubMed ID31417554
'Background: Exposure to stressful stimuli dysregulates inflammatory processes and alters the gut microbiota. Prebiotics, including long-chain fermentable fibers and milk oligosaccharides, have the potential to limit inflammation through modulation of the gut microbiota. To determine whether prebiotics attenuate stress-induced inflammation and microbiota perturbations, mice were fed either a control diet ... More
Integrated Approach Reveals Role of Mitochondrial Germ-Line Mutation F18L in Respiratory Chain, Oxidative Alterations, Drug Sensitivity, and Patient Prognosis in Glioblastoma.
'Glioblastoma is the most common and malignant primary brain tumour in adults, with a dismal prognosis. This is partly due to considerable inter- and intra-tumour heterogeneity. Changes in the cellular energy-producing mitochondrial respiratory chain complex (MRC) activities are a hallmark of glioblastoma relative to the normal brain, and associate with ... More
Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells.
AuthorsKijima T, Nakagawa H, Shimonosono M, Chandramouleeswaran PM, Hara T, Sahu V, Kasagi Y, Kikuchi O, Tanaka K, Giroux V, Muir AB, Whelan KA, Ohashi S, Naganuma S, Klein-Szanto AJ, Shinden Y, Sasaki K, Omoto I, Kita Y, Muto M, Bass AJ, Diehl JA, Ginsberg GG, Doki Y, Mori M, Uchikado Y, Arigami T, Avadhani NG, Basu D, Rustgi AK, Natsugoe S,
JournalCell Mol Gastroenterol Hepatol
PubMed ID30510992
'Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional characterization of cancer cells ex vivo. We investigated the feasibility and the utility of patient-derived ... More
Correlation of miR-425-5p and IL-23 with pancreatic cancer.
AuthorsLu Y, Wu X, Wang J,
JournalOncol Lett
PubMed ID30944648
'The aim of this study was to detect the levels of miR-425-5p and IL-23 in tissues of pancreatic cancer patients and to explore their effects on pancreatic cancer. A retrospective analysis of 76 cases of pancreatic cancer tissue specimens and normal fresh tissue specimens at 50 mm adjacent to the ... More
In Vitro Activity of Statins against Naegleria fowleri.
AuthorsRizo-Liendo A, Sifaoui I, Reyes-Batlle M, Chiboub O, Rodríguez-Expósito RL, Bethencourt-Estrella CJ, San Nicolás-Hernández D, Hendiger EB, López-Arencibia A, Rocha-Cabrera P, Piñero JE, Lorenzo-Morales J,
JournalPathogens
PubMed ID31398829
'Naegleria fowleri causes a deadly disease called primary amoebic meningoencephalitis (PAM). Even though PAM is still considered a rare disease, the number of reported cases worldwide has been increasing each year. Among the factors to be considered for this, awareness about this disease, and also global warming, as these amoebae ... More
Alpha6-Integrin Regulates FGFR1 Expression through the ZEB1/YAP1 Transcription Complex in Glioblastoma Stem Cells Resulting in Enhanced Proliferation and Stemness.
AuthorsKowalski-Chauvel A, Gouaze-Andersson V, Baricault L, Martin E, Delmas C, Toulas C, Cohen-Jonathan-Moyal E, Seva C,
JournalCancers (Basel)
PubMed ID30909436
'Glioblastoma (GBM) is the most lethal primary brain tumor in adults and is known to be particularly aggressive and resistant to anti-cancer therapies, mainly due to the presence of GBM stem cells (GBMSC). By in vitro approaches supported by analysis from patients'' databases, we determined how a6-integrin and Fibroblast Growth ... More
UHRF1 Promotes Proliferation of Human Adipose-Derived Stem Cells and Suppresses Adipogenesis via Inhibiting Peroxisome Proliferator-Activated Receptor ?.
AuthorsChen K, Guo Z, Luo Y, Yuan J, Mo Z,
JournalBiomed Res Int
PubMed ID31428652
'Once the adipose tissue is enlarged for the purpose of saving excess energy intake, obesity may be observed. Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is helpful in repairing damaged DNA as it increases the resistance of cancer cells against cytocidal drugs. Peroxisome proliferator-activated receptor ? (PPAR?), an ... More
Induced Neurons for the Study of Neurodegenerative and Neurodevelopmental Disorders.
'Patient-derived or genomically modified human induced pluripotent stem cells (iPSCs) offer the opportunity to study neurodevelopmental and neurodegenerative disorders. Overexpression of certain neurogenic transcription factors (TFs) in iPSCs can induce efficient differentiation into homogeneous populations of the disease-relevant neuronal cell types. Here we provide protocols for genomic manipulations of iPSCs ... More
Non-Invasive Quantification of the Growth of Cancer Cell Colonies by a Portable Optical Coherence Tomography.
AuthorsTsai MT, Huang BH, Yeh CC, Lei KF, Tsang NM,
JournalMicromachines (Basel)
PubMed ID30621072
'Investigation of tumor development is essential in cancer research. In the laboratory, living cell culture is a standard bio-technology for studying cellular response under tested conditions to predict in vivo cellular response. In particular, the colony formation assay has become a standard experiment for characterizing the tumor development in vitro. ... More
Two novel ANK1 loss-of-function mutations in Chinese families with hereditary spherocytosis.
AuthorsHao L, Li S, Ma D, Chen S, Zhang B, Xiao D, Zhang J, Jiang N, Jiang S, Ma J,
JournalJ Cell Mol Med
PubMed ID31016877
'Hereditary spherocytosis (HS) is the most common inherited haemolytic anaemia disorder. ANK1 mutations account for most HS cases, but pathogenicity analysis and functional research have not been widely performed for these mutations. In this study, in order to confirm diagnosis, gene mutation was screened in two unrelated Chinese families with ... More
PAN-INTACT enables direct isolation of lineage-specific nuclei from fibrous tissues.
AuthorsBhattacharyya S, Sathe AA, Bhakta M, Xing C, Munshi NV,
JournalPLoS One
PubMed ID30939177
'Recent studies have highlighted the extraordinary cell type diversity that exists within mammalian organs, yet the molecular drivers of such heterogeneity remain elusive. To address this issue, much attention has been focused on profiling the transcriptome and epigenome of individual cell types. However, standard cell type isolation methods based on ... More
Hypoxia-inducible factor-1a induces CX3CR1 expression and promotes the epithelial to mesenchymal transition (EMT) in ovarian cancer cells.
AuthorsSingh SK, Mishra MK, Singh R,
JournalJ Ovarian Res
PubMed ID31077234
'Chemokines are involved in the homing of various cancer cells, including those of ovarian cancer (OvCa), to distant organs. They may also promote or inhibit cancer progression and metastasis. Hypoxia, a common phenomenon in malignant tumors, promotes cell proliferation regulated by HIF-1a. Hypoxia-induced genes are involved in metastasis-associated functions and ... More
Drop-on-demand inkjet-based cell printing with 30-µm nozzle diameter for cell-level accuracy.
AuthorsKim YK, Park JA, Yoon WH, Kim J, Jung S
JournalBiomicrofluidics
PubMed ID27990212
We present drop-on-demand inkjet-based mammalian cell printing with a 30-µm nozzle diameter for cell-level accuracy. High-speed imaging techniques have been used to analyze the go-and-stop movement of cells inside the nozzle under a pulsed pressure generated by a piezo-actuator and the jet formation after ejection. Patterning of an array of ... More
Application of polystyrene disk substrates in cellular cultivation methods: generalized specimen preparation protocol for scanning electron microscopy.
AuthorsDeleon H
JournalJ Microsc
PubMed ID27237089
Sample preparation for scanning electron microscopy (SEM) may vary by cellular type, composition and method of cultivation. It has been proposed here that a generalized method of sample preparation may be applied for the visualization of bacteria, fungi, and human cellular tissue without modification of protocol between cell types. The ... More
DNA Damage-Inducible Transcript 4 Is an Innate Surveillant of Hair Follicular Stress in Vitamin D Receptor Knockout Mice and a Regulator of Wound Re-Epithelialization.
AuthorsZhao H, Rieger S, Abe K, Hewison M, Lisse TS
JournalInt J Mol Sci
PubMed ID27898044
Mice and human patients with impaired vitamin D receptor (VDR) signaling have normal developmental hair growth but display aberrant post-morphogenic hair cycle progression associated with alopecia. In addition, VDR(-/-) mice exhibit impaired cutaneous wound healing. We undertook experiments to determine whether the stress-inducible regulator of energy homeostasis, DNA damage-inducible transcript ... More
A novel thiophene-3-carboxamide analog of annonaceous acetogenin exhibits antitumor activity via inhibition of mitochondrial complex I.
AuthorsAkatsuka A, Kojima N, Okamura M, Dan S, Yamori T
JournalPharmacol Res Perspect
PubMed ID28116099
Previously we synthesized JCI-20679, a novel thiophene-3-carboxamide analog of annonaceous acetogenins which have shown potent antitumor activity, with no serious side effects, in mouse xenograft models. In this study, we investigated the antitumor mechanism of JCI-20679. The growth inhibition profile (termed "fingerprint") of this agent across a panel of 39 ... More
Structure and dynamics of a constitutively active neurotensin receptor.
AuthorsKrumm BE, Lee S, Bhattacharya S, Botos I, White CF, Du H, Vaidehi N, Grisshammer R
JournalSci Rep
PubMed ID27924846
Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3?Å crystal structure ... More
DAAs Rapidly Reduce Inflammation but Increase Serum VEGF Level: A Rationale for Tumor Risk during Anti-HCV Treatment.
AuthorsVillani R, Facciorusso A, Bellanti F, Tamborra R, Piscazzi A, Landriscina M, Vendemiale G, Serviddio G
JournalPLoS One
PubMed ID27997563
Novel direct-acting antivirals (DAAs) have completely changed the panorama of hepatitis C due to their high efficacy and optimal safety profile. Unfortunately, an unexpectedly high rate of early recurrence of hepatocellular carcinoma has been reported within weeks of starting treatment, but the mechanism is not known. ... More
Solanine-induced reactive oxygen species inhibit the growth of human hepatocellular carcinoma HepG2 cells.
The aim of the present study was to investigate the effect of solanine on promoting human hepatocellular carcinoma HepG2 cells to produce reactive oxygen species (ROS), and the molecular mechanisms leading to tumor cell apoptosis. Solanine was administered to HepG2 cells in vitro. A selection of probes targeting various cellular ... More
Paper-based microreactor array for rapid screening of cell signaling cascades.
AuthorsHuang CH, Lei KF, Tsang NM
JournalLab Chip
PubMed ID27377153
Investigation of cell signaling pathways is important for the study of pathogenesis of cancer. However, the related operations used in these studies are time consuming and labor intensive. Thus, the development of effective therapeutic strategies may be hampered. In this work, gel-free cell culture and subsequent immunoassay has been successfully ... More
Repertoire comparison of the B-cell receptor-encoding loci in humans and rhesus macaques by next-generation sequencing.
AuthorsVigdorovich V, Oliver BG, Carbonetti S, Dambrauskas N, Lange MD, Yacoob C, Leahy W, Callahan J, Stamatatos L, Sather DN
JournalClin Transl Immunology
PubMed ID27525066
Rhesus macaques (RMs) are a widely used model system for the study of vaccines, infectious diseases and microbial pathogenesis. Their value as a model lies in their close evolutionary relationship to humans, which, in theory, allows them to serve as a close approximation of the human immune system. However, despite ... More
MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder.
AuthorsHeimer G, Kerätär JM, Riley LG, Balasubramaniam S, Eyal E, Pietikäinen LP, Hiltunen JK, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance MA, Shalva N, Veber A, Tzadok M, Nissenkorn A, Tonduti D, Renaldo F, Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Hoffmann C, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B, Hayflick SJ
JournalAm J Hum Genet
PubMed ID27817865
Mitochondrial fatty acid synthesis (mtFAS) is an evolutionarily conserved pathway essential for the function of the respiratory chain and several mitochondrial enzyme complexes. We report here a unique neurometabolic human disorder caused by defective mtFAS. Seven individuals from five unrelated families presented with childhood-onset dystonia, optic atrophy, and basal ganglia ... More
A Toolbox for Rapid Quantitative Assessment of Chronological Lifespan and Survival in Saccharomyces cerevisiae.
AuthorsChadwick SR, Pananos AD, Di Gregorio SE, Park AE, Etedali-Zadeh P, Duennwald ML, Lajoie P
JournalTraffic
PubMed ID26939796
Saccharomyces cerevisiae is a well-established model organism to study the mechanisms of longevity. One of the two aging paradigms studied in yeast is termed chronological lifespan (CLS). CLS is defined by the amount of time non-dividing yeast cells can survive at stationary phase. Here, we propose new approaches that allow ... More
Paramagnetic fluorinated nanoemulsions for sensitive cellular fluorine-19 magnetic resonance imaging.
Fluorine-19 magnetic resonance imaging ((19)F MRI) probes enable quantitative in vivo detection of cell therapies and inflammatory cells. Here, we describe the formulation of perfluorocarbon-based nanoemulsions with improved sensitivity for cellular MRI. Reduction of the (19)F spin-lattice relaxation time (T1) enables rapid imaging and an improved signal-to-noise ratio, thereby improving cell ... More
WNT7A Regulation by miR-15b in Ovarian Cancer.
AuthorsMacLean JA, King ML, Okuda H, Hayashi K
JournalPLoS One
PubMed ID27195958
WNT signaling is well known to play an important role in the regulation of development, cell proliferation and cell differentiation in a wide variety of normal and cancerous tissues. Despite the wealth of knowledge concerning when and where various WNT genes are expressed and downstream events under their control, there ... More
Highly Expressed Integrin-a8 Induces Epithelial to Mesenchymal Transition-Like Features in Multiple Myeloma with Early Relapse.
AuthorsRyu J, Koh Y, Park H, Kim DY, Kim DC, Byun JM, Lee HJ, Yoon SS
JournalMol Cells
PubMed ID28008160
Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after ... More
Investigation of the anti-asthmatic activity of Oridonin on a mouse model of asthma.
AuthorsWang J, Li F, Ding J, Tian G, Jiang M, Gao Z, Tuyghun E
JournalMol Med Rep
PubMed ID27431862
Oridonin is an extract obtained from a traditional Chinese medicinal herb, Xihuangcao. Previous studies have demonstrated that Oridonin exerts various pharmaceutical effects, such as anti-tumor and immunosuppressive effects, as well as modulating cytokine balance. The present study identified that Oridonin could regulate the Th1/Th2 cytokine balance in mice. However, as ... More
Zanthoxylum fruit extract from Japanese pepper promotes autophagic cell death in cancer cells.
AuthorsNozaki R, Kono T, Bochimoto H, Watanabe T, Oketani K, Sakamaki Y, Okubo N, Nakagawa K, Takeda H
JournalOncotarget
PubMed ID27626481
Zanthoxylum fruit, obtained from the Japanese pepper plant (Zanthoxylum piperitum De Candolle), and its extract (Zanthoxylum fruit extract, ZFE) have multiple physiological activities (e.g., antiviral activity). However, the potential anticancer activity of ZFE has not been fully examined. In this study, we investigated the ability of ZFE to induce autophagic ... More
Effect of a feeder layer composed of mouse embryonic and human foreskin fibroblasts on the proliferation of human embryonic stem cells.
AuthorsYang H, Qiu Y, Zeng X, Ding Y, Zeng J, Lu K, Li D,
JournalExp Ther Med
PubMed ID27313670
The aim of the present study was to investigate the effects of feeder layers composed of various ratios of mouse embryonic fibroblasts (MEFs) and human foreskin fibroblasts (hFFs) on the growth of human embryonic stem cells (hESCs). In addition, the secretion levels of basic fibroblast growth factor (bFGF) by the ... More
Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose-Derived Stem Cells.
AuthorsSwioklo S, Constantinescu A, Connon CJ,
JournalStem Cells Transl Med
PubMed ID26826163
: Despite considerable progress within the cell therapy industry, unmet bioprocessing and logistical challenges associated with the storage and distribution of cells between sites of manufacture and the clinic exist. We examined whether hypothermic (4°C-23°C) preservation of human adipose-derived stem cells could be improved through their encapsulation in 1.2% calcium ... More
Anticancer Activity of Garcinia morella on T-Cell Murine Lymphoma Via Apoptotic Induction.
Traditional knowledge (TK) based medicines have gained worldwide attention and presently the scientific community is focussing on proper pharmacological validation and identification of lead compounds for the treatment of various diseases. The North East region of India is the home of valuable traditional herbal remedies. Garcinia morella Desr. (Guttiferae) is ... More
Selective Targeting of Myeloid-Derived Suppressor Cells in Cancer Patients Using DS-8273a, an Agonistic TRAIL-R2 Antibody.
AuthorsDominguez GA, Condamine T, Mony S, Hashimoto A, Wang F, Liu Q, Forero A, Bendell J, Witt R, Hockstein N, Kumar P, Gabrilovich DI
JournalClin Cancer Res
PubMed ID27965309
Purpose: Myeloid-derived suppressor cells (MDSC) are one of the major contributors to immune suppression in cancer. We recently have demonstrated in preclinical study that MDSCs are sensitive to TRAIL receptor 2 (TRAIL-R2) agonist. The goal of this study was to clinically test the hypothesis that targeting TRAIL-R2 can selectively eliminate ... More
Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de-differentiated state.
AuthorsFallahi-Sichani M, Becker V, Izar B, Baker GJ, Lin JR, Boswell SA, Shah P, Rotem A, Garraway LA, Sorger PK
JournalMol Syst Biol
PubMed ID28069687
Treatment of BRAF-mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live-cell imaging, single-cell analysis, and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a ... More
DIVERSet JAG Compounds Inhibit Topoisomerase II and Are Effective Against Adult and Pediatric High-Grade Gliomas.
AuthorsHowarth A, Simms C, Kerai N, Allen O, Mihajluk K, Madureira PA, Sokratous G, Cragg S, Lee SY, Morley AD, Ashkan K, Cox PA, Pilkington GJ, Hill R,
JournalTransl Oncol
PubMed ID31374406
High-grade gliomas (HGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis in both adult and pediatric patients. Clinical response is compounded by resistance to standard frontline antineoplastic agents, an absence of novel therapeutics, and poor in vitro models to evaluate these. We screened a range ... More
Poldip2 deficiency protects against lung edema and vascular inflammation in a model of acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) in a deadly disease that can be brought on by endotoxins such as lipopolysaccharide (LPS). ARDS is characterized by vascular permeability, a severe inflammatory response, lung leukocyte infiltration, and resultant lung edema. Polymerase d-interacting protein 2 (Poldip2) is a novel regulator of blood-brain barrier permeability; ... More
Molecular characterization of foveal versus peripheral human retina by single-cell RNA sequencing.
The human retina is a complex tissue responsible for detecting photons of light and converting information from these photons into the neurochemical signals interpreted as vision. Such visual signaling not only requires sophisticated interactions between multiple classes of neurons, but also spatially-dependent molecular specialization of individual cell types. In this ... More
Dihydrocapsaicin Inhibits Epithelial Cell Transformation through Targeting Amino Acid Signaling and c-Fos Expression.
AuthorsLee JS, Kim YA, Jang YJ, Oh Y, Byun S,
JournalNutrients
PubMed ID31167465
Chili peppers are one of the most widely consumed spices worldwide. However, research on the health benefits of chili peppers and some of its constituents has raised controversy as to whether chili pepper compounds possess cancer-promoting or cancer-preventive effects. While ample studies have been carried out to examine the effect ... More
IL-6 and miR-1271 expression levels in elderly and young gastric cancer patients and correlation analysis with prognosis.
AuthorsLiu S, Zhou Y, Zhao L, Wang J, Ji R, Wang Y, Wu J, Yan X,
JournalOncol Lett
PubMed ID31186760
Differences in inflammatory factors IL-6 and miR-1271 expression levels between elderly and young gastric cancer patients were investigated. A retrospective analysis of 146 cases of gastric cancer tissue and normal fresh tissue specimens diagnosed in The First Hospital of Lanzhou University from January 2013 to January 2015, was performed. Patients ... More
Optimizing Donor Cellular Dissociation and Subretinal Injection Parameters for Stem Cell-Based Treatments.
AuthorsScruggs BA, Jiao C, Cranston CM, Kaalberg E, Wang K, Russell SR, Wiley LA, Mullins RF, Stone EM, Tucker BA, Sohn EH,
JournalStem Cells Transl Med
PubMed ID31004408
Subretinal delivery of stem cell-derived retinal cells as a strategy to treat retinal degenerative blindness holds great promise. Currently, two clinical trials are underway in which human fetal retinal progenitor cells (RPCs) are being delivered to patients by intravitreal or subretinal injection to preserve or restore vision, respectively. With the ... More
Manuka Honey Modulates the Inflammatory Behavior of a dHL-60 Neutrophil Model under the Cytotoxic Limit.
AuthorsMinden-Birkenmaier BA, Cherukuri K, Smith RA, Radic MZ, Bowlin GL,
JournalInt J Biomater
PubMed ID30936919
Recent work has shown that Manuka honey, an increasingly popular wound additive with potent antibacterial properties, also has anti-inflammatory properties. However, little research has been done examining its effect on neutrophils. This study investigates the hypothesis that Manuka honey reduces neutrophil superoxide release and chemotaxis and reduces the activation of ... More
Dandelion Root and Lemongrass Extracts Induce Apoptosis, Enhance Chemotherapeutic Efficacy, and Reduce Tumour Xenograft Growth In Vivo in Prostate Cancer.
AuthorsNguyen C, Mehaidli A, Baskaran K, Grewal S, Pupulin A, Ruvinov I, Scaria B, Parashar K, Vegh C, Pandey S,
JournalEvid Based Complement Alternat Med
PubMed ID31391857
Many conventional chemotherapies have indicated side effects due to a lack of treatment specificity and are thus not suitable for long-term usage. Natural health products are well-tolerated and safe for consumption, and some have pharmaceutical uses particularly for their anticancer effects. We have previously reported the anticancer efficacy of dandelion ... More
Fabrication of thin-layer matrigel-based constructs for three-dimensional cell culture.
AuthorsKo KR, Tsai MC, Frampton JP,
JournalBiotechnol Prog
PubMed ID30315732
Extracellular matrix-based hydrogels such as Matrigel are easy-to-use, commercially available, and offer environments for three-dimensional (3-D) cell culture that mimic native tissue. However, manipulating small volumes of these materials to produce thin-layer 3-D culture systems suitable for analysis is difficult because of air-liquid-substrate interfacial tension effects and evaporation. Here, we ... More
Radiocontrast Agent Diatrizoic Acid Induces Mitophagy and Oxidative Stress via Calcium Dysregulation.
AuthorsWard DB, Brown KC, Valentovic MA,
JournalInt J Mol Sci
PubMed ID31438500
Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital associated kidney damage. Potential mechanisms of CI-AKI may involve diminished renal hemodynamics, inflammatory responses, and direct cytotoxicity. The hypothesis for this study is that diatrizoic acid (DA) induces direct cytotoxicity to human proximal tubule (HK-2) cells via ... More
Regulation of Intronic Polyadenylation by PCF11 Impacts mRNA Expression of Long Genes.
AuthorsWang R, Zheng D, Wei L, Ding Q, Tian B,
JournalCell Rep
PubMed ID30840896
Regulation of cleavage and polyadenylation (CPA) affects gene expression and polyadenylation site (PAS) choice. Here, we report that the CPA and termination factor PCF11 modulates gene expression on the basis of gene size. Although downregulation of PCF11 leads to inhibition of short gene expression, long genes are upregulated because of ... More
Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.
AuthorsOuchi R, Togo S, Kimura M, Shinozawa T, Koido M, Koike H, Thompson W, Karns RA, Mayhew CN, McGrath PS, McCauley HA, Zhang RR, Lewis K, Hakozaki S, Ferguson A, Saiki N, Yoneyama Y, Takeuchi I, Mabuchi Y, Akazawa C, Yoshikawa HY, Wells JM, Takebe T,
JournalCell Metab
PubMed ID31155493
Human organoid systems recapitulate in vivo organ architecture yet fail to capture complex pathologies such as inflammation and fibrosis. Here, using 11 different healthy and diseased pluripotent stem cell lines, we developed a reproducible method to derive multi-cellular human liver organoids composed of hepatocyte-, stellate-, and Kupffer-like cells that exhibit transcriptomic ... More
Targeting BCL-xL improves the efficacy of bromodomain and extra-terminal protein inhibitors in triple-negative breast cancer by eliciting the death of senescent cells.
Inhibitors of bromodomain and extra-terminal proteins (BETi) suppress oncogenic gene expression and have been shown to be efficacious in many in vitro and murine models of cancer, including triple-negative breast cancer (TNBC), a highly aggressive disease. However, in most cancer models, responses to BETi can be highly variable. We previously ... More
Precise Size-Based Cell Separation via the Coupling of Inertial Microfluidics and Deterministic Lateral Displacement.
AuthorsXiang N, Wang J, Li Q, Han Y, Huang D, Ni Z,
JournalAnal Chem
PubMed ID31304740
We report here a novel two-stage i-DLD sorter through coupling inertial microfluidics with deterministic lateral displacement (DLD), allowing for precise, continuous, and size-based cell separation. The first stage spiral inertial microfluidic sorter is responsible for removing the overwhelming majority of background blood cells at a high-throughput manner. The precise and ... More
A proof-of-concept study in HCV-infected Huh7.5 cells for shortening the duration of DAA-based triple treatment regimens.
AuthorsLi H, Tan JL, Li JR, Liu NN, Chen JH, Lv XQ, Zou LL, Dong B, Peng ZG, Jiang JD,
JournalBiomed Pharmacother
PubMed ID31103827
With the development of more effective direct-acting antivirals (DAAs), dual- or triple-therapy regimens represent the major strategy used to cure chronic hepatitis C virus (HCV) infection. Thus, shorter treatment duration regimens with low burden, few adverse effects and good patient adherence are urgently needed. This study theoretically demonstrates a proof-of-concept ... More
Alveolar Differentiation Potency of Human Distal Airway Stem Cells Is Associated with Pulmonary Pathological Conditions.
AuthorsWang Y, Lu Y, Wu Y, Sun Y, Zhou Y, Ma Q, Zheng Y, Yu Q, Cao Y, Chen G, Zhang T, Dai X, Ren T, Ma Y, Zuo W,
JournalStem Cells Int
PubMed ID31281383
This study is aimed at characterizing the human distal airway stem cells (DASCs) and assessing their therapeutic potential in patients with chronic, degenerative lung diseases. These findings will provide a comprehensive understanding for further clinical applications utilizing autologous airway stem cells as therapeutic intervention in respiratory diseases. DASCs were isolated ... More
Identification, cloning and characterization of SpEX exotoxin produced by Staphylococcus pseudintermedius.
AuthorsAbouelkhair MA, Bemis DA, Giannone RJ, Frank LA, Kania SA,
JournalPLoS One
PubMed ID31356636
Staphylococci have evolved numerous strategies to evade their hosts' immune systems. Some staphylococcal toxins target essential components of host innate immunity, one of the two main branches of the immune system. Analysis of the Staphylococcus pseudintermedius secretome using liquid chromatography mass spectrometry guided by genomic data, was used to identify ... More
Suicide gene-armed measles vaccine virus for the treatment of AML.
AuthorsMaurer S, Salih HR, Smirnow I, Lauer UM, Berchtold S,
JournalInt J Oncol
PubMed ID31268165
Virotherapy comprises a novel therapeutic approach to selectively eliminate cancer cells. Preclinical, as well as clinical data have demonstrated the efficacy of tumor-selective (oncolytic) viruses in hematological malignancies. In this study, we infected AML cell lines and primary AML cells from patients with measles vaccine virus either expressing GFP or ... More
Inhibition of host NOX1 blocks tumor growth and enhances checkpoint inhibitor-based immunotherapy.
NADPH oxidases catalyze the production of reactive oxygen species and are involved in physio/pathological processes. NOX1 is highly expressed in colon cancer and promotes tumor growth. To investigate the efficacy of NOX1 inhibition as an anticancer strategy, tumors were grown in immunocompetent, immunodeficient, or NOX1-deficient mice and treated with the ... More
Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes.
Redox-related plasma proteins are candidate reporters of protein signatures associated with endothelial structure/function. Thiol-proteins from protein disulfide isomerase (PDI) family are unexplored in this context. Here, we investigate the occurrence and physiological significance of a circulating pool of PDI in healthy humans. We validated an assay for detecting PDI in ... More
PPARa-Mediated Positive-Feedback Loop Contributes to Cold Exposure Memory.
AuthorsAlfaqaan S, Yoshida T, Imamura H, Tsukano C, Takemoto Y, Kakizuka A,
JournalSci Rep
PubMed ID30872768
Fluctuations in food availability and shifts in temperature are typical environmental changes experienced by animals. These environmental shifts sometimes portend more severe changes; e.g., chilly north winds precede the onset of winter. Such telltale signs may be indicators for animals to prepare for such a shift. Here we show that ... More