Microglia TREM2(R47H) Alzheimer-linked variant enhances excitatory transmission and reduces LTP via increased TNF-α levels.
AuthorsRen S,Yao W,Tambini MD,Yin T,Norris KA,D'Adamio L
JournaleLife
PubMed ID32579116
To study the mechanisms by which the p.R47H variant of the microglia gene and Alzheimerâs disease (AD) risk factor TREM2 increases dementia risk, we created Trem2(R47H) KI rats. Trem2(R47H) rats were engineered to produce human Aβ to define human-Aβ-dependent and -independent pathogenic mechanisms triggered by this variant. Interestingly, pre- and ... More
PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
Enhancing the response to interferon could offer an immunological advantage to the host. In support of this concept, we used a modified form of the transcription factor STAT1 to achieve hyper-responsiveness to interferon without toxicity and markedly improve antiviral function in transgenic mice and transduced human cells. We found that ... More
Unique maternal immune and functional microbial profiles during prenatal stress.
Maternal stress during pregnancy is widespread and is associated with poor offspring outcomes, including long-term mental health issues. Prenatal stress-induced fetal neuroinflammation is thought to underlie aberrant neurodevelopment and to derive from a disruption in intrauterine immune homeostasis, though the exact origins are incompletely defined. We aimed to identify divergent ... More
A puromycin selectable cell line for the enrichment of mouse embryonic stem cell-derived V3 interneurons.
AuthorsXu H,Iyer N,Huettner JE,Sakiyama-Elbert SE
JournalStem cell research & therapy
PubMed ID26555777
INTRODUCTION: Spinal V3 interneurons (INs) are a commissural, glutamatergic, propriospinal neuron population that holds great potential for understanding locomotion circuitry and local rewiring after spinal cord injury. Embryonic stem cells hold promise as a cell source. However, the inevitable heterogeneity resulting from differentiation protocols makes studying post-mitotic stem cell-derived neuron ... More
Electrospun biomaterial scaffolds with varied topographies for neuronal differentiation of human-induced pluripotent stem cells.
AuthorsMohtaram NK,Ko J,King C,Sun L,Muller N,Jun MB,Willerth SM
JournalJournal of biomedical materials research. Part A
PubMed ID25524598
Upregulation of DDAH2 Limits Pulmonary Hypertension and Right Ventricular Hypertrophy During Chronic Hypoxia in Ddah1 Knockout Mice.
AuthorsHannemann J,Glatzel A,Hillig J,Zummack J,Schumacher U,Lüneburg N,Harbaum L,Böger R
JournalFrontiers in physiology
PubMed ID33281630
Objective: Chronic hypoxia causes pulmonary vasoconstriction leading to pulmonary hypertension and right ventricular hypertrophy. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis; its level increases in hypoxia (HX) concomitantly with reduced activity of dimethylarginine dimethylaminohydrolases (DDAH-1 and DDAH-2), enzymes metabolizing ADMA. Ddah1 knockout (KO) mice may ... More
Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.
AuthorsMcCabe KL,Kunzevitzky NJ,Chiswell BP,Xia X,Goldberg JL,Lanza R
JournalPloS one
PubMed ID26689688
AIM: To generate human embryonic stem cell derived corneal endothelial cells (hESC-CECs) for transplantation in patients with corneal endothelial dystrophies. MATERIALS AND METHODS: Feeder-free hESC-CECs were generated by a directed differentiation protocol. hESC-CECs were characterized by morphology, expression of corneal endothelial markers, and microarray analysis of gene expression. RESULTS: hESC-CECs ... More
Attenuated Replication of Lassa Virus Vaccine Candidate ML29 in STAT-1(-/-) Mice.
AuthorsJohnson DM,Jokinen JD,Lukashevich IS
JournalPathogens (Basel, Switzerland)
PubMed ID30650607
Lassa virus (LASV), a highly prevalent mammalian arenavirus endemic in West Africa, can cause Lassa fever (LF), which is responsible for thousands of deaths annually. LASV is transmitted to humans from naturally infected rodents. At present, there is not an effective vaccine nor treatment. The genetic diversity of LASV is ... More
IL-6 trans-Signaling Impairs Sprouting Angiogenesis by Inhibiting Migration, Proliferation and Tube Formation of Human Endothelial Cells.
AuthorsZegeye MM,Andersson B,Sirsjö A,Ljungberg LU
JournalCells
PubMed ID32517159
Sprouting angiogenesis is the formation of new capillaries from existing vessels in response to tissue hypoxia due to growth/development, repair/healing, and also chronic inflammation. In this study, we aimed to elucidate the effect of IL-6, a pleiotropic cytokine with both pro-inflammatory and anti-inflammatory functions, in regulating the sprouting angiogenic response ... More
Development of a bioanalytical method for circulating human T cells in animals using Arthrobacter luteus-based quantitative polymerase chain reaction and its application in preclinical biodistribution studies.
AuthorsShimizu H,Kuze Y,Higuchi T,Matsumoto SI,Yamamoto S,Goto A,Moriya Y,Hirabayashi H
JournalRegenerative therapy
PubMed ID33426226
INTRODUCTION: In the development of cell therapy products for human use, studies on the biodistribution of transplanted cells in animals are important for assessing the safety and efficacy of these products. Although a few reports have described the biodistribution of human cells in animals using Arthrobacter luteus-based-polymerase chain reaction (Alu-PCR), ... More
Serum-free media supplements carry miRNAs that co-purify with extracellular vesicles.
AuthorsAuber M,Fröhlich D,Drechsel O,Karaulanov E,Krämer-Albers EM
JournalJournal of extracellular vesicles
PubMed ID31552133
Recent studies on extracellular RNA raised awareness that extracellular vesicles (EVs) isolated from cultured cells may co-purify RNAs derived from media supplements such as fetal bovine serum (FBS) confounding EV-associated RNA. Defined culture media supplemented with a range of nutrient components provide an alternative to FBS addition and allow EV-collection ... More
Efficient generation of gene-modified human natural killer cells via alpharetroviral vectors.
AuthorsSuerth JD,Morgan MA,Kloess S,Heckl D,Neudörfl C,Falk CS,Koehl U,Schambach A
JournalJournal of molecular medicine (Berlin, Germany)
PubMed ID26300042
Conventional parasitology and DNA-based diagnostic methods for onchocerciasis elimination programmes.
AuthorsLloyd MM,Gilbert R,Taha NT,Weil GJ,Meite A,Kouakou IM,Fischer PU
JournalActa tropica
PubMed ID25818324
Functional Beta2-Integrins Restrict Skin Inflammation In Vivo.
Lyme Disease Risk of Exposure to Blacklegged Ticks (Acari: Ixodidae) Infected with Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in Pittsburgh Regional Parks.
Duchenne muscular dystrophy (DMD) is a lethal, muscle degenerative disease causing premature death of affected children. DMD is characterized by mutations in the dystrophin gene that result in a loss of the dystrophin protein. Loss of dystrophin causes an associated reduction in proteins of the dystrophin glycoprotein complex, leading to ... More
Recombinant Laminins Drive the Differentiation and Self-Organization of hESC-Derived Hepatocytes.
Stem cell-derived somatic cells represent an unlimited resource for basic and translational science. Although promising, there are significant hurdles that must be overcome. Our focus is on the generation of the major cell type of the human liver, the hepatocyte. Current protocols produce variable populations of hepatocytes that are the ... More
Vitamin D Status and Association of VDR Genetic Polymorphism to Risk of Breast Cancer in Ethiopia.
Emerging evidence associates vitamin D deficiency and vitamin D receptor (VDR) genetic variations with risk for breast cancer. This study investigated the prevalence of vitamin D deficiency and its association with tumor characteristics and the implications of VDR genetic variations for risk of breast cancer in Ethiopia. This unmatched caseâcontrol ... More
Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines.
Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we ... More
Localization of Glucagon-Like Peptide-2 Receptor Expression in the Mouse.
AuthorsYusta B,Matthews D,Koehler JA,Pujadas G,Kaur KD,Drucker DJ
JournalEndocrinology
PubMed ID31237617
Glucagon-like peptide-2 (GLP-2), secreted from enteroendocrine cells, attenuates gut motility, enhances barrier function, and augments nutrient absorption, actions mediated by a single GLP-2 receptor (GLP-2R). Despite extensive analyses, the precise distribution and cellular localization of GLP-2R expression remains controversial, confounded by the lack of suitable GLP-2R antisera. Here, we reassessed ... More
Transfer-RNA-Derived Fragments Are Potential Prognostic Factors in Patients with Squamous Cell Carcinoma of the Head and Neck.
AuthorsGu X,Wang L,Coates PJ,Boldrup L,Fåhraeus R,Wilms T,Sgaramella N,Nylander K
JournalGenes
PubMed ID33202812
Transfer-RNA-derived fragments (tRFs) are a class of small non-coding RNAs that are functionally different from their parental transfer RNAs (tRNAs). tRFs can regulate gene expression by several mechanisms, and are involved in a variety of pathological processes. Here, we aimed at understanding the composition and abundance of tRFs in squamous ... More
Combined Use of Gene Expression Modeling and siRNA Screening Identifies Genes and Pathways Which Enhance the Activity of Cisplatin When Added at No Effect Levels to Non-Small Cell Lung Cancer Cells In Vitro.
Platinum-based combination chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). While cisplatin is effective, its use is not curative and resistance often emerges. As a consequence of microenvironmental heterogeneity, many tumour cells are exposed to sub-lethal doses of cisplatin. Further, genomic heterogeneity and unique tumor cell ... More
Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells.
HIV reservoirs and production of viral antigens are not eliminated in chronically infected participants treated with combination antiretroviral therapy (cART). Novel therapeutic strategies aiming at viral reservoir elimination are needed to address chronic immune dysfunction and non-AIDS morbidities that exist despite effective cART. The HIV envelope protein (Env) is emerging ... More
Fibroblast growth factor receptor-1 protein expression is associated with prognosis in estrogen receptor-positive/human epidermal growth factor receptor-2-negative primary breast cancer.
Recently, research into the development of new targeted therapies has focused on specific genetic alterations to create advanced, more personalized treatment. One of the target genes, fibroblast growth factor receptorâ1 (FGFR1), has been reported to be amplified in estrogen receptor (ER)âpositive subtype breast cancer, and is considered one possible mechanism ... More
Sex-related differences in small intestinal transit and serotonin dynamics in high-fat-diet-induced obesity in mice.
Obesity alters gastrointestinal (GI) motility and 5-hydroxytryptamine (5-HT) signaling. Altered 5-HT signaling disrupts control of GI motility. Levels of extracellular 5-HT depend on enterochromaffin (EC) cell release and serotonin transporter (SERT) uptake. We assessed GI transit and 5-HT signaling in the jejunum of normal and obese mice. Male and female ... More
Targeting senescent cells enhances adipogenesis and metabolic function in old age.
Senescent cells accumulate in fat with aging. We previously found genetic clearance of senescent cells from progeroid INK-ATTAC mice prevents lipodystrophy. Here we show that primary human senescent fat progenitors secrete activin A and directly inhibit adipogenesis in non-senescent progenitors. Blocking activin A partially restored lipid accumulation and expression of ... More
Distinct Profiles of Specialized Pro-resolving Lipid Mediators and Corresponding Receptor Gene Expression in Periodontal Inflammation.
Polyunsaturated fatty acid-derived specialized pro-resolving lipid mediators (SPMs) play an important role in modulating inflammation. The aim of the study was to compare profiles of SPMs, SPM related lipid mediators and SPM receptor gene expression in gingiva of subjects with periodontitis to healthy controls. A total of 28 subjects were ... More
Maternal Vitamin D Deficiency Causes Sustained Impairment of Lung Structure and Function and Increases Susceptibility to Hyperoxia-induced Lung Injury in Infant Rats.
AuthorsMandell EW,Ryan S,Seedorf GJ,Gonzalez T,Smith BJ,Fleet JC,Abman SH
JournalAmerican journal of respiratory cell and molecular biology
PubMed ID32135073
Vitamin D deficiency (VDD) during pregnancy is associated with increased respiratory morbidities and risk for chronic lung disease after preterm birth. However, the direct effects of maternal VDD on perinatal lung structure and function and whether maternal VDD increases the susceptibility of lung injury due to hyperoxia are uncertain. In ... More
Modified Alphavirus-Vesiculovirus Hybrid Vaccine Vectors for Homologous Prime-Boost Immunotherapy of Chronic Hepatitis B.
AuthorsChiale C,Yarovinsky TO,Mason SW,Madina BR,Menon M,Krady MM,Moshkani S,Chattopadhyay Pal A,Almassian B,Rose JK,Robek MD,Nakaar V
JournalVaccines
PubMed ID32517032
Virus-like vesicles (VLV) are hybrid vectors based on an evolved Semliki Forest virus (SFV) RNA replicon and the envelope glycoprotein (G) from vesicular stomatitis virus (VSV). Previously, we showed that VLV can be used to express protein antigens and generate protective antigen-specific CD8(+) T cells. This report describes VLV vectors ... More
N-acetylcysteine protects ovarian follicles from ischemia-reperfusion injury in xenotransplanted human ovarian tissue.
JournalAmerican journal of respiratory and critical care medicine
PubMed ID26669357
Rationale: Sequence variation, methylation differences, and transcriptional changes in desmoplakin (DSP) have been observed in patients with idiopathic pulmonary fibrosis (IPF). Objectives: To identify novel variants in DSP associated with IPF and to characterize the relationship of these IPF sequence variants with DSP gene expression in human lung. Methods: A ... More
JournalJournal of the mechanical behavior of biomedical materials
PubMed ID30953806
Craniomaxillofacial bone defects can occur as a result of congenital, post-oncologic, and high-energy impact conditions. The scale and irregularity of such defects motivate new biomaterials to promote regeneration of the damaged bone. We have recently described a mineralized collagen scaffold capable of instructing stem cell osteogenic differentiation and new bone ... More
Bone marrow-derived mesenchymal stem cells improve cognitive impairment in an Alzheimer's disease model by increasing the expression of microRNA-146a in hippocampus.
AuthorsNakano M,Kubota K,Kobayashi E,Chikenji TS,Saito Y,Konari N,Fujimiya M
JournalScientific reports
PubMed ID32612165
Alzheimerâs disease (AD) is characterized by the accumulation of amyloid-β and tau. We previously reported that administration of bone marrow mesenchymal stem cells (BM-MSCs) ameliorates diabetes-induced cognitive impairment by transferring exosomes derived from these cells into astrocytes. Here, we show that intracerebroventricularly injected BM-MSCs improve cognitive impairment in AD model ... More
AuthorsSjöqvist S,Ishikawa T,Shimura D,Kasai Y,Imafuku A,Bou-Ghannam S,Iwata T,Kanai N
JournalJournal of extracellular vesicles
PubMed ID30719240
The oral mucosa exhibits unique regenerative properties, sometimes referred to as foetal-like wound healing. Researchers from our institute have used sheets of oral mucosa epithelial cells (OMECs) for regenerative medicine applications including cornea replacement and oesophageal epithelial regeneration for stricture prevention. Here, we have isolated exosomes from clinical-grade production of ... More
Decreased LIN28B in preeclampsia impairs human trophoblast differentiation and migration.
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
PubMed ID30307771
Preeclampsia (PE) is a common cause of maternal morbidity, characterized by impaired trophoblast invasion and spiral artery transformation resulting in progressive uteroplacental hypoxia. Given the primary role of LIN28A and LIN28B in modulating cell metabolism, differentiation, and invasion, we hypothesized that LIN28A and/or LIN28B regulates trophoblast differentiation and invasion, and ... More
Fluid shear triggers microvilli formation via mechanosensitive activation of TRPV6.
AuthorsMiura S,Sato K,Kato-Negishi M,Teshima T,Takeuchi S
JournalNature communications
PubMed ID26563429
Microvilli are cellular membrane protrusions present on differentiated epithelial cells, which can sense and interact with the surrounding fluid environment. Biochemical and genetic approaches have identified a set of factors involved in microvilli formation; however, the underlying extrinsic regulatory mechanism of microvilli formation remains largely unknown. Here we demonstrate that ... More
Redistribution of EC-SOD resolves bleomycin-induced inflammation via increased apoptosis of recruited alveolar macrophages.
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
PubMed ID31560857
A human single nucleotide polymorphism (SNP) in the matrix-binding domain of extracellular superoxide dismutase (EC-SOD), with arginine to glycine substitution at position 213 (R213G), redistributes EC-SOD from the matrix into extracellular fluids. We reported that, following bleomycin (bleo), knockin mice harboring the human R213G SNP (R213G mice) exhibit enhanced resolution ... More
Erythroid Suppressor Cells Compromise Neonatal Immune Response against Bordetella pertussis.
AuthorsDunsmore G,Bozorgmehr N,Delyea C,Koleva P,Namdar A,Elahi S
JournalJournal of immunology (Baltimore, Md. : 1950)
PubMed ID28779022
Global targetome analysis reveals critical role of miR-29a in pancreatic stellate cell mediated regulation of PDAC tumor microenvironment.
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of malignancies with a nearly equal incidence and mortality rates in patients. Pancreatic stellate cells (PSCs) are critical players in PDAC microenvironment to promote the aggressiveness and pathogenesis of the disease. Dysregulation of microRNAs (miRNAs) have been shown ... More
High Expression of NEK2 and PIM1, but Not PIM3, Is Linked to an Aggressive Phenotype of Bronchopulmonary Neuroendocrine Neoplasms.
AuthorsMotylewska E,Braun M,Stępień H
JournalEndocrine pathology
PubMed ID32504181
Dysregulations of the NEK2 and PIM1-3 kinase signaling axes have been implicated in the pathogenesis of several cancers, including those with a neuroendocrine phenotype. However, their impact on bronchopulmonary neuroendocrine neoplasms (BP-NENs) has not been investigated. The aim of this pilot study was to determine mRNA and protein levels of ... More
5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response.
Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants, but the mechanisms by which they influence behavior are only partially resolved. Adult hippocampal neurogenesis is necessary for some of the responses to SSRIs, but it is unknown whether the mature dentate gyrus granule cells (mature DG GCs) also contribute. We ... More
Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture.
AuthorsHan Z,Li L,Wang L,Degos V,Maze M,Su H
JournalJournal of neurochemistry
PubMed ID25040630
Bone fracture at the acute stage of stroke exacerbates stroke injury by increasing neuroinflammation. We hypothesize that activation of α-7 nicotinic acetylcholine (α-7 nAchR) agonist attenuates neuroinflammation and oxidative stress, and reduces brain injury in mice with bone fracture and stroke. Permanent middle cerebral artery occlusion (pMCAO) was performed in ... More
Decreased Expression of Vitamin D Receptor Affects an Immune Response in Primary Biliary Cholangitis via the VDR-miRNA155-SOCS1 Pathway.
AuthorsKempinska-Podhorodecka A,Milkiewicz M,Wasik U,Ligocka J,Zawadzki M,Krawczyk M,Milkiewicz P
JournalInternational journal of molecular sciences
PubMed ID28146070
Primary biliary cholangitis (PBC) is an immune-mediated cholestatic disease. Vitamin D receptor (VDR)-dependent signaling constrains an inflammatory response by targeting the miRNA155-SOCS1 (suppressor of cytokine signaling 1) axis. The VDR-miRNA155-SOCS1 pathway was investigated in the context of the autoimmune response associated with PBC. Human liver tissues from non-cirrhotic PBC (n ... More
Curative effect of HF10 on liver and peritoneal metastasis mediated by host antitumor immunity.
AuthorsHotta Y,Kasuya H,Bustos I,Naoe Y,Ichinose T,Tanaka M,Kodera Y
JournalOncolytic virotherapy
PubMed ID28331843
BACKGROUND: HF10 is a highly attenuated type 1 herpes simplex virus (HSV) with proven effective oncolytic effect. Previous investigations have demonstrated that colon cancer mice model treated with HF10 not only had better survival but were also resistant to the reimplantation of the antitumor effect mediated by host antitumor immunity. ... More
Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System.
The glymphatic system (GS) hypothesis states that advective driven cerebrospinal fluid (CSF) influx from the perivascular spaces into the interstitial fluid space rapidly transport solutes and clear waste from brain. However, the presence of advection in neuropil is contested and solutes are claimed to be transported by diffusion only. To ... More
Reduction of endoglin receptor impairs mononuclear cell-migration.
AuthorsHan Z,Shaligram S,Faughnan ME,Clark D,Sun Z,Su H
JournalExploration of medicine
PubMed ID32954380
AIM: To test if the impairment of mononuclear cell (MNC) migration in patients with hereditary hemorrhagic telangiectasia (HHT) is due to the reduction of the endoglin (ENG) receptor on the cell surface and oxidative stress. METHODS: MNCs of HHT patients and normal controls were subjected to migration assay. Fractions of ... More
MiR-664 Protects Against UVB Radiation-Induced HaCaT Cell Damage via Downregulating ARMC8.
AuthorsZhang C,Xie X,Yuan Y,Wang Y,Zhou M,Li X,Zhen P
JournalDose-response : a publication of International Hormesis Society
PubMed ID32547335
BACKGROUND: MiR-664 has been demonstrated to play an important role in dermal diseases. However, the functions of miR-664 in ultraviolet B (UVB) radiation-induced keratinocytes damage remain to be elucidated. OBJECTIVE: The present study aimed to investigate the molecular mechanisms under the UVB-induced keratinocytes damage and provide translational insights for future ... More
Endothelial PPAR-γ provides vascular protection from IL-1β-induced oxidative stress.
AuthorsMukohda M,Stump M,Ketsawatsomkron P,Hu C,Quelle FW,Sigmund CD
JournalAmerican journal of physiology. Heart and circulatory physiology
PubMed ID26566726
Loss of peroxisome proliferator-activated receptor (PPAR)-γ function in the vascular endothelium enhances atherosclerosis and NF-κB target gene expression in high-fat diet-fed apolipoprotein E-deficient mice. The mechanisms by which endothelial PPAR-γ regulates inflammatory responses and protects against atherosclerosis remain unclear. To assess functional interactions between PPAR-γ and inflammation, we used a ... More
Conformational Change in the Ligand-Binding Pocket via a KISS1R Mutation (P147L) Leads to Isolated Gonadotropin-Releasing Hormone Deficiency.
AuthorsShimizu K,Yonekawa T,Yoshida M,Miyazato M,Miura A,Sakoda H,Yamaguchi H,Nakazato M
JournalJournal of the Endocrine Society
PubMed ID29264451
CONTEXT: Kisspeptin receptor (KISS1R) is expressed in hypothalamic gonadotropin-releasing hormone neurons and responsible for pubertal onset and reproductive functions. KISS1R mutations remain a rare cause of congenital hypogonadotropic hypogonadism (CHH). OBJECTIVE: The aim of this study was to identify the genetic cause of CHH in a patient and to functionally ... More
An Adaptable High-Throughput Technology Enabling the Identification of Specific Transcription Modulators.
AuthorsBergbrede T,Hoberg E,Larsson NG,Falkenberg M,Gustafsson CM
JournalSLAS discovery : advancing life sciences R & D
PubMed ID28328323
The Effect of Latency Reversal Agents on Primary CD8+ T Cells: Implications for Shock and Kill Strategies for Human Immunodeficiency Virus Eradication.
Shock and kill strategies involving the use of small molecules to induce viral transcription in resting CD4Â + T cells (shock) followed by immune mediated clearance of the reactivated cells (kill), have been proposed as a method of eliminating latently infected CD4Â + T cells. The combination of the histone deacetylase (HDAC) ... More
Molecular Characterization of Somatic Alterations in Dukes' B and C Colorectal Cancers by Targeted Sequencing.
Despite global progress in research, improved screening and refined treatment strategies, colorectal cancer (CRC) remains as the third most common malignancy. As each type of cancer is different and exhibits unique alteration patterns, identifying and characterizing gene alterations in CRC that may serve as biomarkers might help to improve diagnosis, ... More
BDNF/TrkB signaling mediates the anorectic action of estradiol in the nucleus tractus solitarius.
AuthorsShen L,Wang DQH,Xu M,Woods SC,Liu M
JournalOncotarget
PubMed ID29137402
Although compelling evidence indicates that estradiol (E2) acts in the nucleus tractus solitarius (NTS) to reduce food intake, the underlying mechanisms are largely unknown. We now report that estrogen's anorectic action occurs through enhancing the strength of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase (TrkB) signaling in the NTS. ... More
GABA selectively increases mucin-1 expression in isolated pig jejunum.
AuthorsBraun HS,Sponder G,Pieper R,Aschenbach JR,Deiner C
JournalGenes & nutrition
PubMed ID26471792
The inhibitory neurotransmitter GABA (γ-aminobutyric acid) is synthesized by glutamic acid decarboxylase, which is expressed in the central nervous system and in various other tissues including the intestine. Moreover, GABA can be ingested in vegetarian diets or produced by bacterial commensals in the gastrointestinal tract. As previous studies in lung ... More
Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice.
AuthorsLiu N,Jiang Y,Chung JY,Li Y,Yu Z,Kim JW,Lok JM,Whalen MJ,Wang X
JournalInternational journal of molecular sciences
PubMed ID31817350
Our laboratory and others previously showed that Annexin A2 knockout (A2KO) mice had impaired bloodâbrain barrier (BBB) development and elevated pro-inflammatory response in macrophages, implying that Annexin A2 (AnxA2) might be one of the key endogenous factors for maintaining homeostasis of the neurovascular unit in the brain. Traumatic brain injury ... More
ELX-02 Generates Protein via Premature Stop Codon Read-Through without Inducing Native Stop Codon Read-Through Proteins.
AuthorsCrawford DK,Alroy I,Sharpe N,Goddeeris MM,Williams G
JournalThe Journal of pharmacology and experimental therapeutics
PubMed ID32376628
miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice.
AuthorsDusaulcy R,Handgraaf S,Visentin F,Vesin C,Philippe J,Gosmain Y
JournalMolecular metabolism
PubMed ID30711402
OBJECTIVE: Diabetes is a complex disease implicating several organs and cell types. Within the islets, dysregulation occurs in both alpha- and beta-cells, leading to defects of insulin secretion and increased glucagon secretion. Dysregulation of alpha-cells is associated with transcriptome changes. We hypothesized that microRNAs (miRNAs) which are negative regulators of ... More
Increased Catecholamine Levels and Inflammatory Mediators Alter Barrier Properties of Brain Microvascular Endothelial Cells in vitro.
Recent studies have suggested a pathogenetic link between ischemic stroke and Takotsubo cardiomyopathy (TCM) with poor outcome, when occurring simultaneously. Increased catecholamine (CAT) levels as well as elevated inflammatory mediators (INF) are found in the blood of patients with ischemic stroke concomitant with Takotsubo syndrome (TTS). On molecular level, the ... More
A Comprehensive Study of Vesicular and Non-Vesicular miRNAs from a Volume of Cerebrospinal Fluid Compatible with Clinical Practice.
Cerebrospinal fluid (CSF) microRNAs (miRNAs) have emerged as potential biomarkers for minimally invasive diagnosis of central nervous system malignancies. However, despite significant advances in recent years, this field still suffers from poor data reproducibility. This is especially true in cases of infants, considered a new subject group. Implementing efficient methods ... More
Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching.
AuthorsMiyazawa H,Yamaguchi Y,Sugiura Y,Honda K,Kondo K,Matsuda F,Yamamoto T,Suematsu M,Miura M
JournalDevelopment (Cambridge, England)
PubMed ID28049690
Adapting the energy metabolism state to changing bioenergetic demands is essential for mammalian development accompanying massive cell proliferation and cell differentiation. However, it remains unclear how developing embryos meet the changing bioenergetic demands during the chorioallantoic branching (CB) stage, when the maternal-fetal exchange of gases and nutrients is promoted. In ... More
High expression of spliced X-Box Binding Protein 1 in lung tumors is associated with cancer aggressiveness and epithelial-to-mesenchymal transition.
Proteostasis imbalance is emerging as a major hallmark of cancer, driving tumor growth and aggressiveness. Endoplasmic Reticulum (ER) stress has been documented in most major cancers, and the ability to tolerate persistent ER stress through an effective unfolded protein response enhances cancer cell survival, angiogenesis, metastasis, drug resistance and immunosuppression. ... More
Registered report: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs.
AuthorsPhelps M,Coss C,Wang H,Cook M,Reproducibility Project: Cancer Biology,Reproducibility Project Cancer Biology
JournaleLife
PubMed ID26943900
The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and ... More
IDO1 Deficiency Does Not Affect Disease in Mouse Models of Systemic Juvenile Idiopathic Arthritis and Secondary Hemophagocytic Lymphohistiocytosis.
OBJECTIVES: Indoleamine 2,3-dioxygenase-1 (IDO1) is an immune-modulatory enzyme that catalyzes the degradation of tryptophan (Trp) to kynurenine (Kyn) and is strongly induced by interferon (IFN)-γ. We previously reported highly increased levels of IFN-γ and corresponding IDO activity in patients with hemophagocytic lymphohistiocytosis (HLH), a hyper-inflammatory syndrome. On the other hand, ... More
Shared extracellular vesicle miRNA profiles of matched ductal pancreatic adenocarcinoma organoids and blood plasma samples show the power of organoid technology.
JournalCellular and molecular life sciences : CMLS
PubMed ID33237353
Extracellular vesicles (EV) are considered as a promising diagnostic tool for pancreatic ductal adenocarcinoma (PDAC), a disease with a poor 5-year survival that has not improved in the past years. PDAC patient-derived 3D organoids maintain the intratumoral cellular heterogeneity, characteristic for the tumor in vivo.Thus, they represent an ideal in ... More
Modulation of the IL-33/IL-13 Axis in Obesity by IL-13Rα2.
AuthorsDuffen J,Zhang M,Masek-Hammerman K,Nunez A,Brennan A,Jones JEC,Morin J,Nocka K,Kasaian M
JournalJournal of immunology (Baltimore, Md. : 1950)
B-cell precursor acute lymphoblastic leukaemia (B-ALL) is a malignancy of lymphoid progenitor cells with altered genes including the Janus kinase (JAK) gene family. Among them, tyrosine kinase 2 (TYK2) is involved in signal transduction of cytokines such as interferon (IFN) α/β through IFNâα/β receptor alpha chain (IFNAR1). To search for ... More
Pitfalls of DNA Quantification Using DNA-Binding Fluorescent Dyes and Suggested Solutions.
AuthorsNakayama Y,Yamaguchi H,Einaga N,Esumi M
JournalPloS one
PubMed ID26937682
The Qubit fluorometer is a DNA quantification device based on the fluorescence intensity of fluorescent dye binding to double-stranded DNA (dsDNA). Qubit is generally considered useful for checking DNA quality before next-generation sequencing because it measures intact dsDNA. To examine the most accurate and suitable methods for quantifying DNA for ... More
The Effects of Alcohol Intoxication and Burn Injury on the Expression of Claudins and Mucins in the Small and Large Intestines.
AuthorsHammer AM,Khan OM,Morris NL,Li X,Movtchan NV,Cannon AR,Choudhry MA
JournalShock (Augusta, Ga.)
PubMed ID26368926
Alcohol intoxication at the time of burn injury exacerbates post-burn pathogenesis. Recent findings suggest gut barrier integrity is compromised after combined alcohol and burn insult, which could contribute to these complications. Tight junction proteins and mucins play critical roles in keeping the gut barrier intact. Therefore, the goal of this ... More
The neovascularization effect of dedifferentiated fat cells.
Mature adipocyte-derived dedifferentiated fat (DFAT) cells can be prepared efficiently and with minimal invasiveness to the donor. They can be utilized as a source of transplanted cells during therapy. Although the transplantation of DFAT cells into an ischemic tissue enhances angiogenesis and increases vascular flow, there is little information regarding ... More
Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors.
AuthorsAmano I,Takatsuru Y,Toya S,Haijima A,Iwasaki T,Grasberger H,Refetoff S,Koibuchi N
JournalThyroid : official journal of the American Thyroid Association
PubMed ID26914863
Background: Thyroid hormone (TH) plays a key role in the developing brain, including the cerebellum. TH deficiency induces organizational changes of the cerebellum, causing cerebellar ataxia. However, the mechanisms causing these abnormalities are poorly understood. Various animal models have been used to study the mechanism. Lacking dual oxidase (DUOX) and ... More
Stage Specific Expression Pattern of Alpha-Hemoglobin-Stabilizing-Protein (AHSP) Portrayed in Erythroblast Chronology.
AuthorsWalczak J,Camargo Johnson MD,Muthumalaiappan K
JournalMethods and protocols
PubMed ID32629835
During erythropoiesis, the molecular chaperone alpha-hemoglobin-stabilizing protein (AHSP) sequesters free alpha-hemoglobin (αHb) and prevents precipitation of excess αHb. While AHSP is linked to hereditary anemia, the pattern of expression during specific erythroblast stages is poorly understood. We investigated gene and protein expressions of AHSP throughout progressive maturation stages of erythroblasts ... More
Whole-Transcriptome Analysis in Peripheral Blood Mononuclear Cells from Patients with Lipid-Specific Oligoclonal IgM Band Characterization Reveals Two Circular RNAs and Two Linear RNAs as Biomarkers of Highly Active Disease.
The presence of anti-myelin lipid-specific oligoclonal IgM bands (LS-OCMBs) has been defined as an accurate predictor of an aggressive evolution of multiple sclerosis. However, the detection of this biomarker is performed in cerebrospinal fluid, a quite invasive liquid biopsy. In the present study we aimed at studying the expression profile ... More
Feasibility, potency, and safety of growing human mesenchymal stem cells in space for clinical application.
Growing stem cells on Earth is very challenging and limited to a few population doublings. The standard two-dimensional (2D) culture environment is an unnatural condition for cell growth. Therefore, culturing stem cells aboard the International Space Station (ISS) under a microgravity environment may provide a more natural three-dimensional environment for ... More
MicroRNA-21 is a candidate driver gene for 17q23-25 amplification in ovarian clear cell carcinoma.
AuthorsHirata Y,Murai N,Yanaihara N,Saito M,Saito M,Urashima M,Murakami Y,Matsufuji S,Okamoto A
JournalBMC cancer
PubMed ID25366985
BACKGROUND: Epithelial ovarian cancer (EOC) is the most common cause of gynecological malignancy-related mortality. Ovarian clear cell carcinoma (CCC) has unique clinical characteristics and behaviors that differ from other histological types of EOC, including a frequent association with endometriosis and a highly chemoresistant nature, resulting in poor prognosis. However, factors ... More
Immune regulation by glucocorticoids can be linked to cell type-dependent transcriptional responses.
Glucocorticoids remain the most widely used immunosuppressive and anti-inflammatory drugs, yet substantial gaps exist in our understanding of glucocorticoid-mediated immunoregulation. To address this, we generated a pathway-level map of the transcriptional effects of glucocorticoids on nine primary human cell types. This analysis revealed that the response to glucocorticoids is highly ... More
Spread of Amphibian Chytrid Fungus across Lowland Populations of Túngara Frogs in Panamá.
Chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), is an emergent infectious disease partially responsible for worldwide amphibian population declines. The spread of Bd along highland habitats (> 500 meters above sea level, m a.s.l.) of Costa Rica and Panamá is well documented and has been linked to amphibian ... More
Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis.
Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. ... More
Myosin phosphatase isoforms and related transcripts in the pig coronary circulation and effects of exercise and chronic occlusion.
AuthorsZheng X,Heaps CL,Fisher SA
JournalMicrovascular research
PubMed ID24534069
Myosin phosphatase (MP) is a key target of signaling pathways that regulate smooth muscle tone and blood flow. Alternative splicing of MP targeting subunit (MYPT1) exon 24 (E24) generates isoforms with variable presence of a C-terminal leucine zipper (LZ) required for activation of MP by NO/cGMP. Here we examined the ... More
Addition of milk fat globule membrane-enriched supplement to a high-fat meal attenuates insulin secretion and induction of soluble epoxide hydrolase gene expression in the postprandial state in overweight and obese subjects.
CVD and associated metabolic diseases are linked to chronic inflammation, which can be modified by diet. The objective of the present study was to determine whether there is a difference in inflammatory markers, blood metabolic and lipid panels and lymphocyte gene expression in response to a high-fat dairy food challenge ... More
MicroRNA-150 suppresses p27(Kip1) expression and promotes cell proliferation in HeLa human cervical cancer cells.
AuthorsOboshi W,Hayashi K,Takeuchi H,Ikeda K,Yamaguchi Y,Kimura A,Nakamura T,Yukimasa N
JournalOncology letters
PubMed ID32963616
MicroRNAs (miRNAs) exert critical roles in the majority of biological and pathological processes. Recent studies have associated miR-150 with a number of different cancer types. However, little is known about miR-150 targets in cervical cancer. In the present study, the HeLa human cervical cancer cell line was transfected with hsa-miR-150-5p ... More
Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene.
Human SERPINA1 gene is located on chromosome 14q31-32.3 and is organized into three (IA, IB, and IC) non-coding and four (II, III, IV, V) coding exons. This gene produces α1-antitrypsin (A1AT), a prototypical member of the serpin superfamily of proteins. We demonstrate that human peripheral blood leukocytes express not only ... More
Rat Cytomegalovirus Virion-Associated Proteins R131 and R129 Are Necessary for Infection of Macrophages and Dendritic Cells.
Cytomegalovirus (CMV) establishes persistent, latent infection in hosts, causing diseases in immunocompromised patients, transplant recipients, and neonates. CMV infection modifies the host chemokine axis by modulating chemokine and chemokine receptor expression and by encoding putative chemokine and chemokine receptor homologues. The viral proteins have roles in cellular signaling, migration, and ... More
Chikungunya virus superinfection exclusion is mediated by a block in viral replication and does not rely on non-structural protein 2.
AuthorsBoussier J,Levi L,Weger-Lucarelli J,Poirier EZ,Vignuzzi M,Albert ML
JournalPloS one
PubMed ID33180795
Superinfection exclusion (SIE) is a process by which a virally infected cell is protected from subsequent infection by the same or a closely related virus. By preventing cell coinfection, SIE favors preservation of genome integrity of a viral strain and limits its recombination potential with other viral genomes, thereby impacting ... More
CRISPR-Cas9 generated Pompe knock-in murine model exhibits early-onset hypertrophic cardiomyopathy and skeletal muscle weakness.
AuthorsHuang JY,Kan SH,Sandfeld EK,Dalton ND,Rangel AD,Chan Y,Davis-Turak J,Neumann J,Wang RY
JournalScientific reports
PubMed ID32587263
Infantile-onset Pompe Disease (IOPD), caused by mutations in lysosomal acid alpha-glucosidase (Gaa), manifests rapidly progressive fatal cardiac and skeletal myopathy incompletely attenuated by synthetic GAA intravenous infusions. The currently available murine model does not fully simulate human IOPD, displaying skeletal myopathy with late-onset hypertrophic cardiomyopathy. Bearing a Cre-LoxP induced exonic ... More
Role of pharmacogenetics in rifampicin pharmacokinetics and the potential effect on TB-rifampicin sensitivity among Ugandan patients.
AuthorsMukonzo JK,Kengo A,Kutesa B,Nanzigu S,Pohanka A,McHugh TD,Zumla A,Aklillu E
JournalTransactions of the Royal Society of Tropical Medicine and Hygiene
PubMed ID31789383
Telomere dynamics during aging in polygenic left ventricular hypertrophy.
Short telomeres are associated with increased risk of cardiovascular disease. Here we studied cardiomyocyte telomere length at key ages during the ontogeny of cardiac hypertrophy and failure in the hypertrophic heart rat (HHR) and compared these with the normal heart rat (NHR) control strain. Key ages corresponded with the pathophysiological ... More
Rational Targeting of Cooperating Layers of the Epigenome Yields Enhanced Therapeutic Efficacy against AML.
Disruption of epigenetic regulation is a hallmark of AML, but epigenetic therapy is complicated by the complexity of the epigenome. Herein, we developed a long-term primary AML ex vivo platform to determine whether targeting different epigenetic layers with 5-Azacytidine and LSD1 inhibitors would yield improved efficacy. This combination was most ... More
Profile of Pathogenic Proteins and MicroRNAs in Plasma-derived Extracellular Vesicles in Alzheimer's Disease: A Pilot Study.
AuthorsLi F,Xie XY,Sui XF,Wang P,Chen Z,Zhang JB
JournalNeuroscience
PubMed ID32135232
GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand.
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
PubMed ID27466341
Alzheimer's disease (AD) is characterized by the progressive accumulation of amyloid β (Aβ) and microtubule associate protein tau, leading to the selective degeneration of neurons in the neocortex, limbic system, and nucleus basalis, among others. Recent studies have shown that α-synuclein (α-syn) also accumulates in the brains of patients with ... More
COSMC mutations reduce T-synthase activity in advanced Alzheimer's disease.
AuthorsGollamudi S,Lekhraj R,Lalezari S,Lalezari P
JournalAlzheimer's & dementia (New York, N. Y.)
PubMed ID32607408
INTRODUCTION: Mutations in brain tissues that cumulate with age may contribute to Alzheimer's disease (AD). Abnormal glycoprotein and Tn antigen expression have been demonstrated in AD. We identified C1GALT1C1/COSMC mutations in AD and ageâmatched normals without AD. The COSMC coding mutations resulted in a significant reduction in Tâsynthase activity in ... More
Aldehyde dehydrogenase isoforms and inflammatory cell populations are differentially expressed in term human placentas affected by intrauterine growth restriction.
AuthorsChu A,Najafzadeh P,Sullivan P,Cone B,Elshimali R,Shakeri H,Janzen C,Mah V,Wadehra M
JournalPlacenta
PubMed ID31138432
OBJECTIVE: Intrauterine growth restriction (IUGR) is a complication of pregnancy that has both short- and long-term sequelae for affected mothers and offspring. The pathophysiology of disease stems from poor nutrient and oxygen provision to the fetus, resulting in increased oxidative stress within the placenta. As the milieu within the local ... More
IL-33 Augments Virus-Specific Memory T Cell Inflation and Potentiates the Efficacy of an Attenuated Cytomegalovirus-Based Vaccine.
JournalJournal of immunology (Baltimore, Md. : 1950)
PubMed ID30635396
Candidate vaccines designed to generate T cellâbased immunity are typically vectored by nonpersistent viruses, which largely fail to elicit durable effector memory T cell responses. This limitation can be overcome using recombinant strains of CMV. Proof-of-principle studies have demonstrated the potential benefits of this approach, most notably in the SIV ... More
Hepatitis B virus Core protein nuclear interactome identifies SRSF10 as a host RNA-binding protein restricting HBV RNA production.
Despite the existence of a preventive vaccine, chronic infection with Hepatitis B virus (HBV) affects more than 250 million people and represents a major global cause of hepatocellular carcinoma (HCC) worldwide. Current clinical treatments, in most of cases, do not eliminate viral genome that persists as a DNA episome in ... More
Heparin blocks transfer of extracellular vesicles between donor and recipient cells.
Extracellular vesicles (EVs) have been implicated in tumorigenesis. Biomolecules which can block EV binding and uptake into recipient cells may be of therapeutic value as well as enhance understanding of EV biology. Here, we show that heparin interacts with uptake of tumor-derived as well as non-tumor-derived EVs into recipient cells. ... More
In vitro evaluation of osteoprotegerin in chitosan for potential bone defect applications.
AuthorsJayash SN,Hashim NM,Misran M,Baharuddin NA
JournalPeerJ
PubMed ID27635307
BACKGROUND: The receptor activator of nuclear factor kappa-B (RANK)/RANK ligand/osteoprotegerin (OPG) system plays a critical role in bone remodelling by regulating osteoclast formation and activity. OPG has been used systemically in the treatment of bone diseases. In searching for more effective and safer treatment for bone diseases, we investigated newly ... More
Clock Genes Regulate the Circadian Expression of Piezo1, TRPV4, Connexin26, and VNUT in an Ex Vivo Mouse Bladder Mucosa.
OBJECTIVES: Clock(Î19/Î19) mice is an experimental model mouse for nocturia (NOC). Using the bladder mucosa obtained from Clock(Î19/Î19) mice, we investigated the gene expression rhythms of mechanosensory cation channels such as transient receptor potential cation channel subfamily V member 4 (TRPV4) and Piezo1, and main ATP release pathways including vesicular ... More
Thrombopoietin maintains cell numbers of hematopoietic stem and progenitor cells with megakaryopoietic potential.
AuthorsO'Neill A,Chin D,Tan D,Abdul Majeed ABB,Nakamura-Ishizu A,Suda T
JournalHaematologica
PubMed ID32527954
Thrombopoietin has long been known to influence megakaryopoiesis and hematopoietic stem and progenitor cells, although the exact mechanisms through which it acts are unknown. Here we show that MPL expression correlates with megakaryopoietic potential of hematopoietic stem and progenitor cells and identify a population of quiescent hematopoietic stem and progenitor ... More
mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells.
Macrophages and dendritic cells exposed to lipopolysaccharide (LPS) convert their lysosomes from small, punctate organelles into a network of tubules. Tubular lysosomes have been implicated in phagosome maturation, retention of fluid phase, and antigen presentation. There is a growing appreciation that lysosomes act as sensors of stress and the metabolic ... More