Green tea, the fresh leaves of Camellia sinensis, is not only a health-promoting beverage but also a traditional Chinese medicine used for prevention or treatment of cancer, such as lung cancer. Theabrownin (TB) is the main fraction responsible for the medicinal effects of green tea, but whether it possesses anti-cancer ... More
The mGluR5 positive allosteric modulator VU0409551 improves synaptic plasticity and memory of a mouse model of Huntington's disease.
Huntingtonâs Disease (HD) is an autosomal-dominant neurodegenerative disorder, characterized by involuntary body movements, cognitive impairment, and psychiatric disorder. The metabotropic glutamate receptor 5 (mGluR5) plays an important role in HD and we have recently demonstrated that mGluR5-positive allosteric modulators (PAMs) can ameliorate pathology and the phenotypic signs of a mouse ... More
The gene SMART study: method, study design, and preliminary findings.
The gene SMART (genes and the Skeletal Muscle Adaptive Response to Training) Study aims to identify genetic variants that predict the response to both a single session of High-Intensity Interval Exercise (HIIE) and to four weeks of High-Intensity Interval Training (HIIT). While the training and testing centre is located at ... More
A novel regulatory relationship between RIPK4 and ELF3 in keratinocytes.
Dual inhibition of sodium-glucose linked cotransporters 1 and 2 exacerbates cardiac dysfunction following experimental myocardial infarction.
AuthorsConnelly KA,Zhang Y,Desjardins JF,Thai K,Gilbert RE
JournalCardiovascular diabetology
PubMed ID29981571
BACKGROUND: Inhibiting both type 1 and 2 sodiumâglucose linked cotransporter (SGLT1/2) offers the potential to not only increase glucosuria beyond that seen with selective SGLT2 inhibition alone but to reduce glucose absorption from the gut and to thereby also stimulate glucagon-like peptide 1 secretion. However, beyond the kidney and gut, ... More
Influence of the pneumococcal conjugate vaccines on the temporal variation of pneumococcal carriage and the nasal microbiota in healthy infants: a longitudinal analysis of a case-control study.
BACKGROUND: Bacterial colonization of the upper airways is a prerequisite for subsequent invasive disease. With the introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13), changes in pneumococcal upper airway colonization have been described. It is, however, less evident whether the vaccines lead to compositional changes of ... More
TDP-43 Depletion in Microglia Promotes Amyloid Clearance but Also Induces Synapse Loss.
Microglia coordinate various functions in the central nervous system ranging from removing synaptic connections, to maintaining brain homeostasis by monitoring neuronal function, and clearing protein aggregates across the lifespan. Here we investigated whether increased microglial phagocytic activity that clears amyloid can also cause pathological synapse loss. We identified TDP-43, a ... More
Angiopoietin-like 4 induces head and neck squamous cell carcinoma cell migration through the NRP1/ABL1/PXN pathway.
AuthorsHefni E,Menon D,Ma T,Asiedu EB,Sultan A,Meiller T,Schneider A,Sodhi A,Montaner S
JournalCellular signalling
PubMed ID37169211
OBJECTIVES: The molecular mechanisms whereby angiopoietin-like 4 (ANGPTL4), a pluripotent protein implicated in cancer development, contributes to head and neck squamous cell carcinoma (HNSCC) growth and dissemination are unclear. MATERIALS AND METHODS: We investigated ANGPTL4 expression in human normal oral keratinocytes (NOKs), dysplastic oral keratinocytes (DOKs), oral leukoplakia cells (LEUK1), ... More
Source of Dietary Fat in Pig Diet Affects Adipose Expression of Genes Related to Cancer, Cardiovascular, and Neurodegenerative Diseases.
AuthorsOczkowicz M,Szmatoła T,Świątkiewicz M
JournalGenes
PubMed ID31756991
It has been known for many years that excessive consumption of saturated fats has proatherogenic properties, contrary to unsaturated fats. However, the molecular mechanism covering these effects is not fully understood. In this paper, we aimed to identify differentially expressed genes (DEGs) using RNA-sequencing, following feeding pigs with different sources ... More
BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell differentiation.
AuthorsDeason K,Troutman TD,Jain A,Challa DK,Mandraju R,Brewer T,Ward ES,Pasare C
JournalThe Journal of experimental medicine
PubMed ID30093533
The toll-like receptor (TLR) and interleukin (IL)â1 family of receptors share several signaling components, including the most upstream adapter, MyD88. We previously reported the discovery of B cell adapter for phosphoinositide 3-kinase (BCAP) as a novel tollâIL-1 receptor homology domainâcontaining adapter that regulates inflammatory responses downstream of TLR signaling. Here ... More
Three Dimensional Printing Bilayer Membrane Scaffold Promotes Wound Healing.
AuthorsWang S,Xiong Y,Chen J,Ghanem A,Wang Y,Yang J,Sun B
JournalFrontiers in bioengineering and biotechnology
PubMed ID31803738
Full-thickness skin wounds are common and could be a heavy physical and economic burden. With the development of three dimensional (3D) printing technology, skin-like constructs have been fabricated for skin wound healing and regeneration. Although the 3D printed skin has great potential and enormous advantages before vascular networks can be ... More
CD200 Expression Marks a Population of Quiescent Limbal Epithelial Stem Cells with Holoclone Forming Ability.
AuthorsBojic S,Hallam D,Alcada N,Ghareeb A,Queen R,Pervinder S,Buck H,Amitai Lange A,Figueiredo G,Rooney P,Stojkovic M,Shortt A,Figueiredo FC,Lako M
JournalStem cells (Dayton, Ohio)
PubMed ID30157305
GABPA is a master regulator of luminal identity and restrains aggressive diseases in bladder cancer.
TERT promoter mutations occur in the majority of glioblastoma, bladder cancer (BC), and other malignancies while the ETS family transcription factors GABPA and its partner GABPB1 activate the mutant TERT promoter and telomerase in these tumors. GABPA depletion or the disruption of the GABPA/GABPB1 complex by knocking down GABPB1 was ... More
Divergent Functional Diversification Patterns in the SEP/AGL6/AP1 MADS-Box Transcription Factor Superclade.
Members of SEPALLATA (SEP) and APETALA1 (AP1)/SQUAMOSA (SQUA) MADS-box transcription factor subfamilies play key roles in floral organ identity determination and floral meristem determinacy in the rosid species Arabidopsis (Arabidopsis thaliana). Here, we present a functional characterization of the seven SEP/AGL6 and four AP1/SQUA genes in the distant asterid species ... More
Human glioblastoma-associated microglia/monocytes express a distinct RNA profile compared to human control and murine samples.
MPS-IIIA mice acquire autistic behaviours with age.
AuthorsLau AA,Tamang SJ,Hemsley KM
JournalJournal of inherited metabolic disease
PubMed ID29520737
FUT2 Secretor Status Is Not Associated With Oral Poliovirus Vaccine Immunogenicity in South Indian Infants.
AuthorsParker EPK,Whitfield H,Baskar C,Giri S,John J,Grassly NC,Kang G,Praharaj I
JournalThe Journal of infectious diseases
PubMed ID30239830
FUT2 determines whether histo-blood group antigens are secreted at mucosal surfaces. Secretor status influences susceptibility to enteric viruses, potentially including oral poliovirus vaccine (OPV). We performed a nested caseâcontrol study to determine the association between FUT2 genotype (single-nucleotide polymorphisms G428A, C302T, and A385T) and seroconversion among Indian infants who received ... More
A Combined Linkage and GWAS Analysis Identifies QTLs Linked to Soybean Seed Protein and Oil Content.
JournalInternational journal of molecular sciences
PubMed ID31775326
Soybean is an excellent source of vegetable protein and edible oil. Understanding the genetic basis of protein and oil content will improve the breeding programs for soybean. Linkage analysis and genome-wide association study (GWAS) tools were combined to detect quantitative trait loci (QTL) that are associated with protein and oil ... More
A systems biology approach reveals neuronal and muscle developmental defects after chronic exposure to ionising radiation in zebrafish.
AuthorsMurat El Houdigui S,Adam-Guillermin C,Loro G,Arcanjo C,Frelon S,Floriani M,Dubourg N,Baudelet E,Audebert S,Camoin L,Armant O
JournalScientific reports
PubMed ID31882844
Contamination of the environment after the Chernobyl and Fukushima Daiichi nuclear power plant (NPP) disasters led to the exposure of a large number of humans and wild animals to radioactive substances. However, the sub-lethal consequences induced by these absorbed radiological doses remain understudied and the long-term biological impacts largely unknown. ... More
Relationships between the Abundance and Expression of Functional Genes from Vinyl Chloride (VC)-Degrading Bacteria and Geochemical Parameters at VC-Contaminated Sites.
AuthorsLiang Y,Liu X,Singletary MA,Wang K,Mattes TE
JournalEnvironmental science & technology
PubMed ID28981261
The Skin Commensal Yeast Malassezia Triggers a Type 17 Response that Coordinates Anti-fungal Immunity and Exacerbates Skin Inflammation.
The DUX4 transcription factor is briefly expressed in the early cleavage-stage embryo, where it induces an early wave of zygotic gene transcription, whereas its mis-expression in skeletal muscle causes the muscular dystrophy facioscapulohumeral dystrophy (FSHD). Here, we show that DUX4 induces the expression of the histone variants H3.X and H3.Y. ... More
Microbial mechanisms and ecosystem flux estimation for aerobic NO(y) emissions from deciduous forest soils.
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID30659144
Reactive nitrogen oxides (NO(y); NO(y) = NO + NO(2) + HONO) decrease air quality and impact radiative forcing, yet the factors responsible for their emission from nonpoint sources (i.e., soils) remain poorly understood. We investigated the factors that control the production of aerobic NO(y) in forest soils using molecular techniques, ... More
Enhancement of Cellular Adhesion and Proliferation in Human Mesenchymal Stromal Cells by the Direct Addition of Recombinant Collagen I Peptide to the Culture Medium.
AuthorsMuraya K,Kawasaki T,Yamamoto T,Akutsu H
JournalBioResearch open access
PubMed ID31763065
Mesenchymal stromal cells (MSCs) have considerable potential for a wide range of clinical applications and regenerative medicine and cell therapy. As a consequence, there is considerable interest in developing robust culture methods for producing large number of MSCs for use in repair of injured tissues or treatment of diseases. In ... More
Quantification of Pneumocystis jirovecii: Cross-Platform Comparison of One qPCR Assay with Leading Platforms and Six Master Mixes.
AuthorsDellière S,Gits-Muselli M,White PL,Mengoli C,Bretagne S,Alanio A
JournalJournal of fungi (Basel, Switzerland)
PubMed ID31888050
Diagnosis of Pneumocystis jirovecii pneumonia relies on nucleic acid quantification in respiratory samples. Lack of standardization among molecular assays results in significant differences among assays/centers. To further promote standardization, we compared four thermocyclers and six master mixes for the detection of P. jirovecii. Whole nucleic acid (WNA) was extracted from ... More
Tetrabromobisphenol-A Promotes Early Adipogenesis and Lipogenesis in 3T3-L1 Cells.
AuthorsChappell VA,Janesick A,Blumberg B,Fenton SE
JournalToxicological sciences : an official journal of the Society of Toxicology
PubMed ID30496566
Tetrabromobisphenol A (TBBPA) is the most common flame retardant used in electrical housings, circuit boards, and automobiles. High-throughput screening and binding assays have identified TBBPA as an agonist for human peroxisome proliferator-activated receptor gamma (PPARγ), the master regulator of adipogenesis. TBBPA has been suggested to be an obesogen based on ... More
Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells.
JournalInternational journal of molecular sciences
PubMed ID31801200
Paracrine factors can induce cardiac regeneration and repair post myocardial infarction by stimulating proliferation of cardiac cells and inducing the anti-fibrotic, antiapoptotic, and immunomodulatory effects of angiogenesis. Here, we screened a human secretome library, consisting of 923 growth factors, cytokines, and proteins with unknown function, in a phenotypic screen with ... More
TIP60 up-regulates ΔNp63α to promote cellular proliferation.
An estimated 5.4 million cases of nonmelanoma skin cancer are reported in the United States at an associated cost of $4.8 billion. ÎNp63α, a proto-oncogene in the p53 family of transcription factors, is overexpressed in squamous cell carcinoma (SCC) and associated with poor prognosis and survival. ÎNp63α elicits its tumorigenic ... More
NKG2D and Its Ligand MULT1 Contribute to Disease Progression in a Mouse Model of Multiple Sclerosis.
AuthorsLegroux L,Moratalla AC,Laurent C,Deblois G,Verstraeten SL,Arbour N
JournalFrontiers in immunology
PubMed ID30787931
NKG2D is an activating receptor expressed on the surface of immune cells including subsets of T lymphocytes. NKG2D binds multiple ligands (NKG2DL) whose expression are differentially triggered in a cell type and stress specific manner. The NKG2D-NKG2DL interaction has been involved in autoimmune disorders but its role in animal models ... More
Protein Kinase R Is Constitutively Expressed in the Human Pancreas.
AuthorsJonsson A,Yngve E,Karlsson M,Ingvast S,Skog O,Korsgren O
JournalThe journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
PubMed ID30265185
Viral infection of the insulin-producing cells in the pancreas has been proposed in the etiology of type 1 diabetes. Protein kinase R (PKR) is a cytoplasmic protein activated through phosphorylation in response to cellular stress and particularly viral infection. As PKR expression in pancreatic beta-cells has been interpreted as a ... More
Mycobacterium tuberculosis Drives Expansion of Low-Density Neutrophils Equipped With Regulatory Activities.
AuthorsLa Manna MP,Orlando V,Paraboschi EM,Tamburini B,Di Carlo P,Cascio A,Asselta R,Dieli F,Caccamo N
JournalFrontiers in immunology
PubMed ID31849955
In human tuberculosis (TB) neutrophils represent the most commonly infected phagocyte but their role in protection and pathology is highly contradictory. Moreover, a subset of low-density neutrophils (LDNs) has been identified in TB, but their functions remain unclear. Here, we have analyzed total neutrophils and their low-density and normal-density (NDNs) ... More
IVIVC Assessment of Two Mouse Brain Endothelial Cell Models for Drug Screening.
Since most preclinical drug permeability assays across the blood-brain barrier (BBB) are still evaluated in rodents, we compared an in vitro mouse primary endothelial cell model to the mouse b.End3 and the acellular parallel artificial membrane permeability assay (PAMPA) models for drug screening purposes. The mRNA expression of key feature ... More
lncRNA/mRNA profiling of endometriosis rat uterine tissues during the implantation window.
AuthorsCai H,Zhu X,Li Z,Zhu Y,Lang J
JournalInternational journal of molecular medicine
PubMed ID31638262
Endometriosis is associated with changes in long non-coding RNA (lncRNA) and mRNA expression, but the exact changes during the implantation window are unknown. Therefore, this study aimed to explore the lncRNA and mRNA expression profiles in the uterus of rats with endometriosis during the implantation window. A total of 35 ... More
Zinc Deficiency During Pregnancy Leads to Altered Microbiome and Elevated Inflammatory Markers in Mice.
AuthorsSauer AK,Grabrucker AM
JournalFrontiers in neuroscience
PubMed ID31849598
Zinc is an essential trace metal for bacteria of the intestinal flora. Approximately 20% of dietary zinc â intake is used by intestinal bacteria. The microbiome has recently been described as an important factor for healthy brain function via so-called gut-brain interactions. Similarly, zinc deficiency has been associated with neurological ... More
High-throughput screening identifies histone deacetylase inhibitors that modulate GTF2I expression in 7q11.23 microduplication autism spectrum disorder patient-derived cortical neurons.
BACKGROUND: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition affecting almost 1% of children, and represents a major unmet medical need with no effective drug treatment available. Duplication at 7q11.23 (7Dup), encompassing 26â28 genes, is one of the best characterized ASD-causing copy number variations and offers unique translational ... More
Assessment of the Association of D2 Dopamine Receptor Gene and Reported Allele Frequencies With Alcohol Use Disorders: A Systematic Review and Meta-analysis.
AuthorsJung Y,Montel RA,Shen PH,Mash DC,Goldman D
JournalJAMA network open
PubMed ID31702801
IMPORTANCE: The association between the D2 dopamine receptor gene (DRD2) Taq1A locus (rs1800497) and alcohol use disorder (AUD) is enduring but the subject of long-standing controversy; meta-analysis of studies across 3 decades shows an association between rs1800497 and AUD, but genome-wide analyses have detected no role for rs1800497 in any ... More
Impact of Free-Choice Diets High in Fat and Different Sugars on Metabolic Outcome and Anxiety-Like Behavior in Rats.
OBJECTIVE: Rats were exposed to freeâchoice diets (fat plus one of two different sugar solutions, glucose or sucrose), and the metabolic consequences and impact on locomotor activity and anxietyâlike behavior were explored. METHODS: For 3 weeks, 7âweekâold male rats were offered either chow only or freeâchoice highâfat diets differing in ... More
Region-specific microRNA alterations in marmosets carrying SLC6A4 polymorphisms are associated with anxiety-like behavior.
AuthorsPopa N,Bachar D,Roberts AC,Santangelo AM,Gascon E
JournalEBioMedicine
PubMed ID35905539
BACKGROUND: Psychiatric diseases such as depression and anxiety are multifactorial conditions, highly prevalent in western societies. Human studies have identified a number of high-risk genetic variants for these diseases. Among them, polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) have attracted much attention. However, due to the ... More
Adipose-derived autotaxin regulates inflammation and steatosis associated with diet-induced obesity.
AuthorsBrandon JA,Kraemer M,Vandra J,Halder S,Ubele M,Morris AJ,Smyth SS
JournalPloS one
PubMed ID30730895
Autotaxin (ATX) is a secreted enzyme that generates the bioactive lipid lysophosphatidic acid (LPA). We generated mice with global inducible post-natal inactivation or adipose-specific loss of the Enpp2 gene encoding ATX. The animals are phenotypically unremarkable and exhibit differences in adipocyte size and adipose tissue expression of inflammatory genes after ... More
The regulation of sequence specific NF-κB DNA binding and transcription by IKKβ phosphorylation of NF-κB p50 at serine 80.
Phosphorylation of the NF-κB transcription factor is an important regulatory mechanism for the control of transcription. Here we identify serine 80 (S80) as a phosphorylation site on the p50 subunit of NF-κB, and IKKβ as a p50 kinase. Transcriptomic analysis of cells expressing a p50 S80A mutant reveals a critical ... More
Verification of hub genes in the expression profile of aortic dissection.
BACKGROUND: To assess the mRNA expression profile and explore the hub mRNAs and potential molecular mechanisms in the pathogenesis of human thoracic aortic dissection (TAD). METHODOLOGY: mRNA microarray expression signatures of TAD tissues (n = 6) and non-TAD tissues (NT; n = 6) were analyzed by an Arraystar human mRNA ... More
Evaluation of NV556, a Novel Cyclophilin Inhibitor, as a Potential Antifibrotic Compound for Liver Fibrosis.
Hepatic fibrosis can result as a pathological response to nonalcoholic steatohepatitis (NASH). Cirrhosis, the late stage of fibrosis, has been linked to poor survival and an increased risk of developing hepatocellular carcinoma, with limited treatment options available. Therefore, there is an unmet need for novel effective antifibrotic compounds. Cyclophilins are ... More
Oligomeric Forms of Human Amyloid-Beta(1-42) Inhibit Antigen Presentation.
Genetic, clinical, biochemical and histochemical data indicate a crucial involvement of inflammation in Alzheimer's disease (AD), but harnessing the immune system to cure or prevent AD has so far proven difficult. Clarifying the cellular heterogeneity and signaling pathways associated with the presence of the AD hallmarks beta-amyloid and tau in ... More
Improving engraftment of hepatocyte transplantation using alpha-1 antitrypsin as an immune modulator.
JournalJournal of molecular medicine (Berlin, Germany)
PubMed ID30820592
ABSTRACT: For patients with non-cirrhotic liver-based metabolic disorders, hepatocyte transplantation can be an effective treatment. However, long-term function of transplanted hepatocytes following infusion has not been achieved due to insufficient numbers of hepatocytes reaching the liver cell plates caused by activation of the instant blood-mediated inflammatory reaction (IBMIR). Our aim ... More
Sprayable and biodegradable, intrinsically adhesive wound dressing with antimicrobial properties.
AuthorsDaristotle JL,Lau LW,Erdi M,Hunter J,Djoum A Jr,Srinivasan P,Wu X,Basu M,Ayyub OB,Sandler AD,Kofinas P
JournalBioengineering & translational medicine
PubMed ID31989038
Conventional wound dressings are difficult to apply to large total body surface area (TBSA) wounds, as they typically are prefabricated, require a layer of adhesive coating for fixation, and need frequent replacement for entrapped exudate. Large TBSA wounds as well as orthopedic trauma and lowâresource surgery also have a high ... More
Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy.
Adoptive cell therapy represents a new paradigm in cancer immunotherapy but can be limited by poor persistence and function of transferred T cells(1). Here, through an in vivo pooled CRISPR-Cas9 mutagenesis screening, we demonstrate that CD8(+) T cells are reprogrammed to long-lived effector cells with extensive accumulation, better persistence and ... More
Droplet-based vitrification of adherent human induced pluripotent stem cells on alginate microcarrier influenced by adhesion time and matrix elasticity.
Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression.
AuthorsLim PH,Wert SL,Tunc-Ozcan E,Marr R,Ferreira A,Redei EE
JournalBehavioural brain research
PubMed ID29490235
Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis.
Chronic psychological stress is closely correlated with breast cancer growth and metastasis. Sini San (SNS) formula is a classical prescription for relieving depression-related symptoms in traditional Chinese medicine (TCM). Current researches have suggested that chronic psychological stress is closely correlated with cancer stem cells (CSCs) and endoplasmic reticulum (ER) stress. ... More
Development of Mithramycin Analogues with Increased Selectivity toward ETS Transcription Factor Expressing Cancers.
Mithramycin A (1) was identified as the top potential inhibitor of the aberrant ETS transcription factor EWS-FLI1, which causes Ewing sarcoma. Unfortunately, 1 has a narrow therapeutic window, compelling us to seek less toxic and more selective analogues. Here, we used MTMSA (2) to generate analogues via peptide coupling and ... More
Ablation of RIP3 protects from dopaminergic neurodegeneration in experimental Parkinson's disease.
Parkinsonâs disease (PD) is driven by dopaminergic neurodegeneration in the substantia nigra pars compacta (SN) and striatum. Although apoptosis is considered the main neurodegenerative mechanism, other cell death pathways may be involved. In this regard, necroptosis is a regulated form of cell death dependent on receptor interacting protein 3 (RIP3), ... More
Genome-wide Discovery and Identification of a Novel miRNA Signature for Recurrence Prediction in Stage II and III Colorectal Cancer.
JournalClinical cancer research : an official journal of the American Association for Cancer Research
PubMed ID29514841
PURPOSE: The current TNM (Tumor Node Metastasis) staging system is inadequate at identifying high-risk colorectal cancer (CRC) patients. Using a systematic and comprehensive-biomarker discovery and validation approach, we aimed to identify a miRNA-recurrence classifier (MRC) that can improve upon the current TNM-staging as well as superior to currently offered molecular ... More
FGF19 Analog as a Surgical Factor Mimetic That Contributes to Metabolic Effects Beyond Glucose Homeostasis.
AuthorsDePaoli AM,Zhou M,Kaplan DD,Hunt SC,Adams TD,Learned RM,Tian H,Ling L
JournalDiabetes
PubMed ID30862680
An experimental genetically attenuated live vaccine to prevent transmission of Toxoplasma gondii by cats.
Almost any warm-blooded creature can be an intermediate host for Toxoplasma gondii. However, sexual reproduction of T. gondii occurs only in felids, wherein fertilisation of haploid macrogametes by haploid microgametes, results in diploid zygotes, around which a protective wall develops, forming unsporulated oocysts. Unsporulated oocysts are shed in the faeces ... More
Common Cervicovaginal Microbial Supernatants Alter Cervical Epithelial Function: Mechanisms by Which Lactobacillus crispatus Contributes to Cervical Health.
AuthorsAnton L,Sierra LJ,DeVine A,Barila G,Heiser L,Brown AG,Elovitz MA
JournalFrontiers in microbiology
PubMed ID30349508
Cervicovaginal (CV) microbiota is associated with vaginal health and disease in non-pregnant women. Recent studies in pregnant women suggest that specific CV microbes are associated with preterm birth (PTB). While the associations between CV microbiota and adverse outcomes have been demonstrated, the mechanisms regulating the associations remain unclear. As the ... More
Evaluation and optimization of differentiation conditions for human primary brown adipocytes.
As an effective way to improve energy expenditure, increasing the mass and activity of brown adipose tissue (BAT) has become a promising treatment for obesity and its associated disorders. Many efforts have been made to promote brown adipogenesis and increase the thermogenic capacity of brown adipose cells (BACs). The present ... More
Cellular abundance of sodium phosphate cotransporter SLC20A1/PiT1 and phosphate uptake are controlled post-transcriptionally by ESCRT.
AuthorsZechner C,Henne WM,Sathe AA,Xing C,Hernandez G,Sun S,Cheong MC
JournalThe Journal of biological chemistry
PubMed ID35447110
Inorganic phosphate is essential for human life. The widely expressed mammalian sodium/phosphate cotransporter SLC20A1/PiT1 mediates phosphate uptake into most cell types; however, while SLC20A1 is required for development, and elevated SLC20A1 expression is associated with vascular calcification and aggressive tumor growth, the mechanisms regulating SLC20A1 protein abundance are unknown. Here, ... More
Effects of the dual orexin receptor antagonist DORA-22 on sleep in 5XFAD mice.
INTRODUCTION: Sleep disruption is a characteristic of Alzheimer's disease (AD) that may exacerbate disease progression. This study tested whether a dual orexin receptor antagonist (DORA) would enhance sleep and attenuate neuropathology, neuroinflammation, and cognitive deficits in an AD-relevant mouse model, 5XFAD. METHODS: Wild-type (C57Bl6/SJL) and 5XFAD mice received chronic treatment ... More
Saturated fatty acid regulated lncRNA dataset during in vitro human embryonic neurogenesis.
AuthorsArdah MT,Parween S,Varghese DS,Emerald BS,Ansari SA
JournalData in brief
PubMed ID30450400
Human embryonic stem cells (hESCs) were used as a model of embryonic neurogenesis to identify the effect of excess fat uptake on neurodevelopment (Ardah et al., 2018). Herein, by directed differentiation of hESCs into neurons using established protocols, this data was generated for expression profiles of select lncRNAs during in ... More
Early-Life Antibiotic-Driven Dysbiosis Leads to Dysregulated Vaccine Immune Responses in Mice.
It is recognized that the behavioral rhythms of organisms are controlled by the circadian clock, while the reverse direction, i.e., whether changes in physiology and behavior react to the internal rhythms, is unclear. Cryptochromes (CRYs) are photolyase-like flavoproteins with blue-light receptor function and other functions on circadian clock and migration ... More
Finely tuned conformational dynamics regulate the protective function of the lncRNA MALAT1 triple helix.
Nucleic acid triplexes may regulate many important biological processes. Persistent accumulation of the oncogenic 7-kb long noncoding RNA MALAT1 is dependent on an unusually long intramolecular triple helix. This triplex structure is positioned within a conserved ENE (element for nuclear expression) motif at the lncRNA 3â² terminus and protects the ... More
LXR-inverse agonism stimulates immune-mediated tumor destruction by enhancing CD8 T-cell activity in triple negative breast cancer.
AuthorsCarpenter KJ,Valfort AC,Steinauer N,Chatterjee A,Abuirqeba S,Majidi S,Sengupta M,Di Paolo RJ,Shornick LP,Zhang J,Flaveny CA
JournalScientific reports
PubMed ID31863071
Triple-negative breast cancer (TNBC) is a highly aggressive subtype that is untreatable with hormonal or HER2-targeted therapies and is also typically unresponsive to checkpoint-blockade immunotherapy. Within the tumor microenvironment dysregulated immune cell metabolism has emerged as a key mechanism of tumor immune-evasion. We have discovered that the Liver-X-Receptors (LXRα and ... More
Modulators of insulin secretion could be used to treat diabetes and as tools to investigate β cell regulatory pathways in order to increase our understanding of pancreatic islet function. Toward this goal, we previously used an insulin-linked luciferase that is cosecreted with insulin in MIN6 β cells to perform a ... More
Distinct patterns of innate immune activation by clinical isolates of respiratory syncytial virus.
Respiratory syncytial virus (RSV) is a major respiratory pathogen of infants and young children. Multiple strains of both subgroup A and B viruses circulate during each seasonal epidemic. Genetic heterogeneity among RSV genomes, in large part due to the error prone RNA-dependent, RNA polymerase, could mediate variations in pathogenicity. We ... More
Autophagy Alters the Susceptibility of Candida albicans Biofilms to Antifungal Agents.
AuthorsShen J,Ma M,Duan W,Huang Y,Shi B,Wu Q,Wei X
JournalMicroorganisms
PubMed ID37630575
Candida albicans (C. albicans) reigns as a major cause of clinical candidiasis. C. albicans biofilms are known to increase resistance to antifungal agents, making biofilm-related infections particularly challenging to treat. Drug resistance is of particular concern due to the spread of multidrug-resistant fungal pathogens, while autophagy is crucial for the ... More
An SFTPC BRICHOS mutant links epithelial ER stress and spontaneous lung fibrosis.
Alveolar type 2 (AT2) cell endoplasmic reticulum (ER) stress is a prominent feature in adult and pediatric interstitial lung disease (ILD and ChILD), but in vivo models linking AT2 cell ER stress to ILD have been elusive. Based on a clinical ChILD case, we identified a critical cysteine residue in ... More
Transcriptomic Analyses Revealed Systemic Alterations in Gene Expression in Circulation and Tumor Microenvironment of Colorectal Cancer Patients.
Colorectal cancer (CRC) is among the leading causes of cancer-related deaths worldwide, underscoring a need for better understanding of the disease and development of novel diagnostic biomarkers and therapeutic interventions. Herein, we performed transcriptome analyses on peripheral blood mononuclear cells (PBMCs), CRC tumor tissue and adjacent normal tissue from 10 ... More
Persistence of Candida albicans in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression.
Controlled immune activation in response to commensal microbes is critical for the maintenance of stable colonization and prevention of microbial overgrowth on epithelial surfaces. Our understanding of the host mechanisms that regulate bacterial commensalism has increased substantially, however, much less data exist regarding host responses to members of the fungal ... More
Therapeutic FGF19 promotes HDL biogenesis and transhepatic cholesterol efflux to prevent atherosclerosis.
AuthorsZhou M,Learned RM,Rossi SJ,Tian H,DePaoli AM,Ling L
JournalJournal of lipid research
PubMed ID30679232
Fibroblast growth factor (FGF)19, an endocrine hormone produced in the gut, acts in the liver to control bile acid synthesis. NGM282, an engineered FGF19 analog, is currently in clinical development for treating nonalcoholic steatohepatitis. However, the molecular mechanisms that integrate FGF19 with cholesterol metabolic pathways are incompletely understood. Here, we ... More
METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m(6)A Modification.
N(6)-methyladenosine (m(6)A), the most prevalent internal modification in eukaryotic messenger RNAs (mRNAs), plays critical roles in many bioprocesses. However, its functions in normal and malignant hematopoiesis remain elusive. Here we report METTL14, a key component of the m(6)A methyltransferase complex, is highly expressed in normal hematopoietic stem/progenitor cells (HSPCs) and ... More
Epigenetically mediated inhibition of S-adenosylhomocysteine hydrolase and the associated dysregulation of 1-carbon metabolism in nonalcoholic steatohepatitis and hepatocellular carcinoma.
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
PubMed ID29127188
The substantial rise in the prevalence of nonalcoholic steatohepatitis (NASH), an advanced form of nonalcoholic fatty liver disease, and the strong association between NASH and the development of hepatocellular carcinoma indicate the urgent need for a better understanding of the underlying mechanisms. In the present study, by using the Stelic ... More
FOXM1 Deubiquitination by USP21 Regulates Cell Cycle Progression and Paclitaxel Sensitivity in Basal-like Breast Cancer.
The transcription factor FOXM1 contributes to cell cycle progression and is significantly upregulated in basal-like breast cancer (BLBC). Despite its importance in normal and cancer cell cycles, we lack a complete understanding of mechanisms that regulate FOXM1. We identified USP21 in an RNAi-based screen for deubiquitinases that control FOXM1 abundance. ... More
BET bromodomain inhibitors and agonists of the beta-2 adrenergic receptor identified in screens for compounds that inhibit DUX4 expression in FSHD muscle cells.
AuthorsCampbell AE,Oliva J,Yates MP,Zhong JW,Shadle SC,Snider L,Singh N,Tai S,Hiramuki Y,Tawil R,van der Maarel SM,Tapscott SJ,Sverdrup FM
JournalSkeletal muscle
PubMed ID28870238
BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is a progressive muscle disease caused by mutations that lead to epigenetic derepression and inappropriate transcription of the double homeobox 4 (DUX4) gene in skeletal muscle. Drugs that enhance the repression of DUX4 and prevent its expression in skeletal muscle cells therefore represent candidate therapies for ... More
BAP1 induces cell death via interaction with 14-3-3 in neuroblastoma.
BRCA1-associated protein 1 (BAP1) is a nuclear deubiquitinating enzyme that is associated with multiprotein complexes that regulate key cellular pathways, including cell cycle, cellular differentiation, cell death, and the DNA damage response. In this study, we found that the reduced expression of BAP1 pro6motes the survival of neuroblastoma cells, and ... More
Sex-specific differences in the modulation of Growth Differentiation Factor 15 (GDF15) by hyperoxia in vivo and in vitro: Role of Hif-1α.
AuthorsZhang Y,Jiang W,Wang L,Lingappan K
JournalToxicology and applied pharmacology
PubMed ID28734801
Male premature neonates are more susceptible than females to the development of bronchopulmonary dysplasia (BPD). The reasons underlying sexually dimorphic outcomes in premature neonates are not known. GDF15 (Growth and differentiation factor 15) is a secreted cytokine and plays a role in cell proliferation, apoptosis, and angiogenesis. In this study, ... More
The wheat SnRK1α family and its contribution to Fusarium toxin tolerance.
AuthorsPerochon A,Váry Z,Malla KB,Halford NG,Paul MJ,Doohan FM
JournalPlant science : an international journal of experimental plant biology
PubMed ID31521211
Transcriptome Analyses of Female Somatotropes and Lactotropes Reveal Novel Regulators of Cell Identity in the Pituitary.
AuthorsPeel MT,Ho Y,Liebhaber SA
JournalEndocrinology
PubMed ID30247555
The differentiation of the hormone-producing cell lineages of the anterior pituitary represents an informative model of mammalian cell fate determination. The generation and maintenance of two of these lineages, the GH-producing somatotropes and prolactin (PRL)-producing lactotropes, are dependent on the pituitary-specific transcription factor POU1F1. Whereas POU1F1 is expressed in both ... More
Genetic Risk for Psychiatric Disorders and Telomere Length.
Background: Previous studies have revealed associations between psychiatric disorder diagnosis and shorter telomere length. Here, we attempt to discern whether genetic risk for psychiatric disorders, or use of pharmacological treatments (i.e., antidepressants), predict shorter telomere length and risk for aging-related disease in a United Kingdom population sample. Methods: DNA samples ... More
Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma due to cell cycle regulation and cellular stress.
Encoded by EEF1A1, the eukaryotic translation elongation factor eEF1α1 strongly promotes the heat shock response, which protects cancer cells from proteotoxic stress, following for instance oxidative stress, hypoxia or aneuploidy. Unexpectedly, therefore, we find that EEF1A1 mRNA levels are reduced in virtually all breast cancers, in particular in ductal carcinomas. ... More
Mechanism of Chronic Stress-induced Reduced Atherosclerotic Medial Area and Increased Plaque Instability in Rabbit Models of Chronic Stress.
AuthorsYu ZM,Deng XT,Qi RM,Xiao LY,Yang CQ,Gong T
JournalChinese medical journal
PubMed ID29336364
BACKGROUND: Chronic stress contributes to increased risks of atherosclerotic diseases including heart disease, stroke, and transient ischemic attack. However, its underline mechanisms are poorly understood. This study aimed to elucidate the mechanism via which chronic stress exerts its effect on atherosclerosis (AS). METHODS: Fifty male New Zealand white rabbits were ... More
The effect of antiretroviral treatment on selected genes in whole blood from HIV-infected adults sensitised by Mycobacterium tuberculosis.
AuthorsJhilmeet N,Lowe DM,Riou C,Scriba TJ,Coussens A,Goliath R,Wilkinson RJ,Wilkinson KA
JournalPloS one
PubMed ID30589870
HIV-1 co-infection is a leading cause of susceptibility to tuberculosis (TB), with the risk of TB being increased at all stages of HIV-1 infection. Antiretroviral treatment (ART) is the most effective way to reduce the risk of TB in HIV-1 co-infected people. Studying protective, ART-induced, immune restoration in HIV-1 infected ... More
Intra-Articular Injection of Fructus Ligustri Lucidi Extract Attenuates Pain Behavior and Cartilage Degeneration in Mono-Iodoacetate Induced Osteoarthritic Rats.
Fructus Ligustri Lucidi (FLL) has been widely used as a traditional Chinese medicine (TCM) for treating soreness and weakness of waist and knees. It has potential for treating OA owing to its kidney-tonifying activity with bone-strengthening effects, but there is so far no report of its anti-OA effect. This study ... More
AuthorsMikaeili H,Sandi M,Bayot A,Al-Mahdawi S,Pook MA
JournalScientific reports
PubMed ID30464193
Friedreich ataxia (FRDA) is a multisystem genetic disorder caused by GAA repeat expansion mutations within the FXN gene, resulting in heterochromatin formation and deficiency of frataxin protein. Elevated levels of the FXN antisense transcript (FAST-1) have previously been detected in FRDA. To investigate the effects of FAST-1 on the FXN ... More
Lrp6 is a target of the PTH-activated αNAC transcriptional coregulator.
AuthorsPellicelli M,Hariri H,Miller JA,St-Arnaud R
JournalBiochimica et biophysica acta. Gene regulatory mechanisms
PubMed ID29413898
Empagliflozin Improves Diastolic Function in a Nondiabetic Rodent Model of Heart Failure With Preserved Ejection Fraction.
AuthorsConnelly KA,Zhang Y,Visram A,Advani A,Batchu SN,Desjardins JF,Thai K,Gilbert RE
JournalJACC. Basic to translational science
PubMed ID30847416
Recent studies send an unambiguous signal that the class of agents known as sodium-glucoseâlinked co-transporter-2Â inhibitors (SGLT2i) prevent heart failure hospitalization in patients with type 2 diabetes. However, the mechanisms remain unclear. Herein the authors utilize a rodent model of heart failure with preserved ejection fraction (HFpEF), and demonstrate that treatment ... More
An Easy and Efficient Strategy for the Enhancement of Epothilone Production Mediated by TALE-TF and CRISPR/dcas9 Systems in Sorangium cellulosum.
AuthorsYe W,Liu T,Zhu M,Zhang W,Huang Z,Li S,Li H,Kong Y,Chen Y
JournalFrontiers in bioengineering and biotechnology
PubMed ID32039165
Epothilones are a kind of macrolides with strong cytotoxicity toward cancer cells and relatively lower side effects compared with taxol. Epothilone B derivate ixabepilone has been used for the clinical treatment of advanced breast cancer. However, the low yield of epothilones and the difficulty in the genetic manipulation of Sorangium ... More
Adenovirus-mediated ubiquitination alters protein-RNA binding and aids viral RNA processing.
Viruses promote infection by hijacking host ubiquitin machinery to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defenses and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing ... More
Altered expression of Sialyl Lewis X in experimental models of Parkinson's disease.
AuthorsNunes MJ,Carvalho AN,Rosa AI,Videira PA,Gama MJ,Rodrigues E,Castro-Caldas M
JournalJournal of molecular medicine (Berlin, Germany)
PubMed ID38197965
ABSTRACT: The mechanisms underlying neurodegeneration in Parkinsonâs disease (PD) are still not fully understood. Glycosylation is an important post-translational modification that affects protein function, cell-cell contacts and inflammation and can be modified in pathologic conditions. Although the involvement of aberrant glycosylation has been proposed for PD, the knowledge of the ... More
Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes.
Bleomycin hydrolase (BLMH) is a well-conserved cysteine protease widely expressed in several mammalian tissues. In skin, which contains high levels of BLMH, this protease is involved in the degradation of citrullinated filaggrin monomers into free amino acids important for skin hydration. Interestingly, the expression and activity of BLMH is reduced ... More
A dual regulatory circuit consisting of S-adenosylmethionine decarboxylase protein and its reaction product controls expression of the paralogous activator prozyme in Trypanosoma brucei.
AuthorsPatel MM,Volkov OA,Leija C,Lemoff A,Phillips MA
JournalPLoS pathogens
PubMed ID30365568
Polyamines are essential for cell growth of eukaryotes including the etiologic agent of human African trypanosomiasis (HAT), Trypanosoma brucei. In trypanosomatids, a key enzyme in the polyamine biosynthetic pathway, S-adenosylmethionine decarboxylase (TbAdoMetDC) heterodimerizes with a unique catalytically-dead paralog called prozyme to form the active enzyme complex. In higher eukaryotes, polyamine ... More
Association of colistin residues and manure treatment with the abundance of mcr-1 gene in swine feedlots.
Cell cycle arrest in mitosis promotes interferon-induced necroptosis.
AuthorsFrank T,Tuppi M,Hugle M,Dötsch V,van Wijk SJL,Fulda S
JournalCell death and differentiation
PubMed ID30742091
Resistance to apoptosis is a hallmark of cancer and deregulation of apoptosis often leads to chemoresistance. Therefore, new approaches to target apoptosis-resistant cancer cells are crucial for the development of directed cancer therapies. In the present study, we investigated the effect of cell cycle regulators on interferon (IFN)-induced necroptosis as ... More
MicroRNA Expression Profiling Predicts Nodal Status and Disease Recurrence in Patients Treated with Curative Intent for Colorectal Cancer.
AuthorsDavey MG,Feeney G,Annuk H,Paganga M,Holian E,Lowery AJ,Kerin MJ,Miller N
JournalCancers
PubMed ID35565239
SIMPLE SUMMARY: Determining the degree of nodal involvement provides key prognostic information in several malignancies, including colorectal cancer (CRC). Furthermore, predicting long-term outcomes in such cancers often proves challenging to the multidisciplinary team. Therefore, the purpose of this translational research study was to evaluate the role of mi(cro)RNAs as biomarkers ... More
MicroRNA profiling of the pig periaqueductal grey (PAG) region reveals candidates potentially related to sex-dependent differences.
AuthorsPawlina-Tyszko K,Oczkowicz M,Gurgul A,Szmatoła T,Bugno-Poniewierska M
JournalBiology of sex differences
PubMed ID33451362
BACKGROUND: MicroRNAs indirectly orchestrate myriads of essential biological processes. A wide diversity of miRNAs of the neurodevelopmental importance characterizes the brain tissue, which, however, exhibits region-specific miRNA profile differences. One of the most conservative regions of the brain is periaqueductal grey (PAG) playing vital roles in significant functions of this ... More
Tumor-Derived Extracellular Vesicles Inhibit Natural Killer Cell Function in Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Tumor-derived extracellular vesicles (EVs) induce pre-metastatic niche formation to promote metastasis. We isolated EVs from a highly-metastatic pancreatic cancer cell line and patient-derived primary cancer cells by ultracentrifugation. The protein content of EVs was analyzed by mass spectrometry. The ... More
Novel sequence variants in the TLR6 gene associated with advanced breast cancer risk in the Saudi Arabian population.
Herein, we evaluated the association of the Toll-like receptor 6 (TLR6) single nucleotide polymorphisms (SNPs) rs3796508 (Val327Met) and rs5743810 (Ser249Pro) with breast cancer (BC) susceptibility in Saudi Arabian women, using in silico analysis. We found no significant differences in genotypic and allelic frequencies for rs3796508 between the BC patients (n ... More
Hyperactive FOXO1 results in lack of tip stalk identity and deficient microvascular regeneration during kidney injury.
Loss of the microvascular (MV) network results in tissue ischemia, loss of tissue function, and is a hallmark of chronic diseases. The incorporation of a functional vascular network with that of the host remains a challenge to utilizing engineered tissues in clinically relevant therapies. We showed that vascular-bed-specific endothelial cells ... More
LCDR regulates the integrity of lysosomal membrane by hnRNP K-stabilized LAPTM5 transcript and promotes cell survival.
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID35091468
Lysosome plays important roles in cellular homeostasis, and its dysregulation contributes to tumor growth and survival. However, the understanding of regulation and the underlying mechanism of lysosome in cancer survival is incomplete. Here, we reveal a role for a histone acetylationâregulated long noncoding RNA termed lysosome cell death regulator (LCDR) ... More