scholarly journals miR-210 and GPD1L regulate EDN2 in primary and immortalized human granulosa-lutein cells

Reproduction ◽  
2018 ◽  
Vol 155 (2) ◽  
pp. 197-205 ◽  
Author(s):  
Ketan Shrestha ◽  
Adepeju Esther Onasanya ◽  
Iris Eisenberg ◽  
Noa Wigoda ◽  
Simcha Yagel ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Cell Types ◽  
Vital Role ◽  
The Novel ◽  
Gene Target ◽  
Hypoxic Induction ◽  
Its Gene ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Mimetic Compound ◽  
Cyclase Activator

Endothelin-2 (EDN2), expressed at a narrow window during the periovulatory period, critically affects ovulation and corpus luteum (CL) formation. LH (acting mainly via cAMP) and hypoxia are implicated in CL formation; therefore, we aimed to elucidate how these signals regulate EDN2 using human primary (hGLCs) and immortalized (SVOG) granulosa-lutein cells. The hypoxiamiR, microRNA-210 (miR-210) was identified as a new essential player in EDN2 expression. Hypoxia (either mimetic compound-CoCl2, or low O2) elevated hypoxia-inducible factor 1A (HIF1A), miR-210 and EDN2. Hypoxia-induced miR-210 was suppressed in HIF1A-silenced SVOG cells, suggesting that miR-210 is HIF1A dependent. Elevated miR-210 levels in hypoxia or by miR-210 overexpression, increased EDN2. Conversely, miR-210 inhibition reduced EDN2 levels, even in the presence of CoCl2, indicating the importance of miR-210 in the hypoxic induction of EDN2. A molecule that destabilizes HIF1A protein, glycerol-3-phosphate dehydrogenase 1-like gene-GPD1L, was established as a miR-210 target in both cell types. It was decreased by miR-210-mimic and was increased by miR-inhibitor. Furthermore, reducing GPD1L by endogenously elevated miR-210 (in hypoxia), miR-210-mimic or by GPD1L siRNA resulted in elevated HIF1A protein and EDN2 levels, implying a vital role for GPD1L in the hypoxic induction of EDN2. Under normoxic conditions, forskolin (adenylyl cyclase activator) triggered changes typical of hypoxia. It elevated HIF1A, EDN2 and miR-210 while inhibiting GPD1L. Furthermore, HIF1A silencing greatly reduced forskolin’s ability to elevate EDN2 and miR-210. This study highlights the novel regulatory roles of miR-210 and its gene target, GPD1L, in hypoxia and cAMP-induced EDN2 by human granulosa-lutein cells.

scholarly journals A Mathematical Model of Contact Tracing during the 2014–2016 West African Ebola Outbreak

Mathematics ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 608
Author(s):  
Danielle Burton ◽  
Suzanne Lenhart ◽  
Christina J. Edholm ◽  
Benjamin Levy ◽  
Michael L. Washington ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Disease Management ◽  
Ebola Virus ◽  
Virus Disease ◽  
Infected Individual ◽  
Vital Role ◽  
West African ◽  
Contact Tracing ◽  
The Novel ◽  
Using Data

The 2014–2016 West African outbreak of Ebola Virus Disease (EVD) was the largest and most deadly to date. Contact tracing, following up those who may have been infected through contact with an infected individual to prevent secondary spread, plays a vital role in controlling such outbreaks. Our aim in this work was to mechanistically represent the contact tracing process to illustrate potential areas of improvement in managing contact tracing efforts. We also explored the role contact tracing played in eventually ending the outbreak. We present a system of ordinary differential equations to model contact tracing in Sierra Leonne during the outbreak. Using data on cumulative cases and deaths, we estimate most of the parameters in our model. We include the novel features of counting the total number of people being traced and tying this directly to the number of tracers doing this work. Our work highlights the importance of incorporating changing behavior into one’s model as needed when indicated by the data and reported trends. Our results show that a larger contact tracing program would have reduced the death toll of the outbreak. Counting the total number of people being traced and including changes in behavior in our model led to better understanding of disease management.

scholarly journals Current Understanding of Exosomal MicroRNAs in Glioma Immune Regulation and Therapeutic Responses

2022 ◽  
Vol 12 ◽  
Author(s):  
Jinwu Peng ◽  
Qiuju Liang ◽  
Zhijie Xu ◽  
Yuan Cai ◽  
Bi Peng ◽  
...  
Keyword(s):  
Immune Regulation ◽  
Response Prediction ◽  
Cell Types ◽  
Clinicopathological Characteristics ◽  
The Novel ◽  
Multiple Cancer ◽  
Exosomal Mirnas ◽  
Multiple Cell ◽  
Almost All ◽  
Therapeutic Responses

Exosomes, the small extracellular vesicles, are released by multiple cell types, including tumor cells, and represent a novel avenue for intercellular communication via transferring diverse biomolecules. Recently, microRNAs (miRNAs) were demonstrated to be enclosed in exosomes and therefore was protected from degradation. Such exosomal miRNAs can be transmitted to recipient cells where they could regulate multiple cancer-associated biological processes. Accumulative evidence suggests that exosomal miRNAs serve essential roles in modifying the glioma immune microenvironment and potentially affecting the malignant behaviors and therapeutic responses. As exosomal miRNAs are detectable in almost all kinds of biofluids and correlated with clinicopathological characteristics of glioma, they might be served as promising biomarkers for gliomas. We reviewed the novel findings regarding the biological functions of exosomal miRNAs during glioma pathogenesis and immune regulation. Furthermore, we elaborated on their potential clinical applications as biomarkers in glioma diagnosis, prognosis and treatment response prediction. Finally, we summarized the accessible databases that can be employed for exosome-associated miRNAs identification and functional exploration of cancers, including glioma.

scholarly journals Candida aechmeae sp. nov. and Candida vrieseae sp. nov., novel yeast species isolated from the phylloplane of bromeliads in Southern Brazil

2010 ◽  
Vol 60 (1) ◽  
pp. 244-248 ◽  
Author(s):  
Melissa Fontes Landell ◽  
Raisa Billodre ◽  
Jesus P. Ramos ◽  
Orílio Leoncini ◽  
Marilene H. Vainstein ◽  
...  
Keyword(s):  
Type Strain ◽  
Yeast Species ◽  
Novel Species ◽  
Sequence Divergence ◽  
Rrna Gene ◽  
The Novel ◽  
D2 Domain ◽  
Its Gene ◽  
Ascomycetous Yeasts ◽  
Positive Results

Two novel yeast species, Candida aechmeae sp. nov. and Candida vrieseae sp. nov., were isolated from bromeliads in Itapuã Park, Rio Grande do Sul, Brazil. These species are genetically isolated from all other currently recognized ascomycetous yeasts based on their sequence divergence in the D1/D2 domain of the LSU rRNA gene. C. aechmeae sp. nov. is phylogenetically close to Candida ubatubensis, a species also isolated from bromeliads in Brazil, but the novel species can be differentiated on the basis of differences in the D1/D2 domain and positive results for the assimilation of l-arabinose, raffinose, inulin and citrate. Candida vrieseae sp. nov. is phylogenetically placed in a clade near Candida membranifaciens that is composed of several species associated with insects, but the novel species can be differentiated from them by the D1/D2 and ITS gene sequences, positive results for the assimilation of nitrite and a negative result for the assimilation of ethylamine. The type strain for Candida aechmeae sp. nov. is BI153T (=CBS 10831T=NRRL Y-48456T) and the type strain for C. vrieseae sp. nov. is BI146T (=CBS 10829T=NRRL Y-48461T).

scholarly journals The Novel WD-repeat Protein Morg1 Acts as a Molecular Scaffold for Hypoxia-inducible Factor Prolyl Hydroxylase 3 (PHD3)

2006 ◽  
Vol 281 (13) ◽  
pp. 8645-8655 ◽  
Author(s):  
Ulrike Hopfer ◽  
Helmut Hopfer ◽  
Katarina Jablonski ◽  
Rolf A. K. Stahl ◽  
Gunter Wolf
Keyword(s):  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
The Novel ◽  
Molecular Scaffold ◽  
Repeat Protein ◽  
Wd Repeat

Applications of Gold Nanoparticles in Cancer

2017 ◽  
pp. 194-229
Author(s):  
Solaimuthu Balakrishnan ◽  
Firdous Ahmad Bhat ◽  
Arunakaran Jagadeesan
Keyword(s):  
Drug Delivery ◽  
Gold Nanoparticles ◽  
Drug Delivery Systems ◽  
Protein Detection ◽  
Local Environment ◽  
Controlled Drug Release ◽  
Cell Types ◽  
The Novel ◽  
Gold Core ◽  
Novel Drug

This chapter deals with the applications of gold nanoparticle in cancer and various strategies to target cancer cells by using gold nanoparticles. They are in great demand for biomedical applications such as DNA/Protein detection, bimolecular regulators, cell imaging and cancer cell diagnostics. The ability to tune the surface of the particle provides access to cell –specific targeting and controlled drug release. Depending on their size, shape, degree of aggregation, and local environment, gold nanoparticles can appear red, blue, or other colors. The novel drug delivery systems offer the opportunity to improve poor solubility, limited stability, bio distribution, and pharmacokinetics of drug as well as offering the potential ability to target specific tissues and cell types. The multifunctional gold nanoparticles are attractive organic –inorganic hybrid material composed of an inorganic metallic gold core surrounded by an organic or bimolecular monolayer they provide desirable attributes for the creation of drug delivery in cancer.

scholarly journals A novel missense variant c.G644A (p.G215E) of the RPGR gene in a Chinese family causes X-linked retinitis pigmentosa

2019 ◽  
Vol 39 (10) ◽  
Author(s):  
Jiewen Fu ◽  
Jingliang Cheng ◽  
Qi Zhou ◽  
Chunli Wei ◽  
Hanchun Chen ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Expression Patterns ◽  
Missense Variant ◽  
Vital Role ◽  
Chinese Family ◽  
The Novel ◽  
Rna Seq ◽  
Targeted Next Generation Sequencing ◽  
Retinal Tissue ◽  
Eye Tissues

Abstract The mutations in patients with X-linked retinitis pigmentosa (xlRP) have not been well described in the Chinese population. In the present study, a five-generation Chinese retinitis pigmentosa (RP) family was recruited; targeted next-generation sequencing (TGS) was used to identify causative genes and Sanger sequencing for co-segregation. RNA-seq data analysis and revere transcriptional-polymerase chain reaction (RT-PCR) were applied to investigate gene expression patterns of RP GTPase regulator (RPGR) in human and Rpgr in mouse. A novel, hemizygous, deleterious and missense variant: c.G644A (p.G215E) in the RPGR gene (NM_000328.2) exon 7 of X-chromosome was identified in the proband, which was co-segregated with the clinical phenotypes in this family. RNA-seq data showed that RPGR is ubiquitously expressed in 27 human tissues with testis in highest, but no eye tissues data. Then the expressions for Rpgr mRNA in mice including eye tissues were conducted and showed that Rpgr transcript is ubiquitously expressed very highly in retina and testis, and highly in other eye tissues including lens, sclera, and cornea; and expressed highly in the six different developmental times of retinal tissue. Ubiquitous expression in different tissues from eye and very high expression in the retina indicated that RPGR plays a vital role in eye functions, particularly in retina. In conclusion, our study is the first to indicate that the novel missense variant c.G644A (p.G215E) in the RPGR gene might be the disease-causing mutation in this xlRP family, expanding mutation spectrum. These findings facilitate better understanding of the molecular pathogenesis of this disease; provide new insights for genetic counseling and healthcare.

scholarly journals Extracellular Vesicle as a Source of Alzheimer’s Biomarkers: Opportunities and Challenges

2019 ◽  
Vol 20 (7) ◽  
pp. 1728 ◽  
Author(s):  
Seongju Lee ◽  
Sakulrat Mankhong ◽  
Ju-Hee Kang
Keyword(s):  
Clinical Evidence ◽  
Biological Function ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Vital Role ◽  
Synaptic Loss ◽  
Memory Decline ◽  
Disease Propagation ◽  
The Central Nervous System ◽  
Yield And Purity

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease characterized by memory decline and cognitive dysfunction. Although the primary causes of AD are not clear, it is widely accepted that the accumulation of amyloid beta (Aβ) and consecutive hyper-phosphorylation of tau, synaptic loss, oxidative stress and neuronal death might play a vital role in AD pathogenesis. Recently, it has been widely suggested that extracellular vesicles (EVs), which are released from virtually all cell types, are a mediator in regulating AD pathogenesis. Clinical evidence for the diagnostic performance of EV-associated biomarkers, particularly exosome biomarkers in the blood, is also emerging. In this review, we briefly introduce the biological function of EVs in the central nervous system and discuss the roles of EVs in AD pathogenesis. In particular, the roles of EVs associated with autophagy and lysosomal degradation systems in AD proteinopathy and in disease propagation are discussed. Next, we summarize candidates for biochemical AD biomarkers in EVs, including proteins and miRNAs. The accumulating data brings hope that the application of EVs will be helpful for early diagnostics and the identification of new therapeutic targets for AD. However, at the same time, there are several challenges in developing valid EV biomarkers. We highlight considerations for the development of AD biomarkers from circulating EVs, which includes the standardization of pre-analytical sources of variability, yield and purity of isolated EVs and quantification of EV biomarkers. The development of valid EV AD biomarkers may be facilitated by collaboration between investigators and the industry.

scholarly journals Impact of naturally forming human α/β-tryptase heterotetramers in the pathogenesis of hereditary α-tryptasemia

2019 ◽  
Vol 216 (10) ◽  
pp. 2348-2361 ◽  
Author(s):  
Quang T. Le ◽  
Jonathan J. Lyons ◽  
Andrea N. Naranjo ◽  
Ana Olivera ◽  
Robert A. Lazarus ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mast Cells ◽  
Clinical Features ◽  
Hormone Receptor ◽  
Cell Types ◽  
The Novel ◽  
Monogenic Disorder ◽  
Α Subunit ◽  
Gene Copies ◽  
Protease Activated Receptor 2

Both α-tryptase and β-tryptase are preferentially expressed by human mast cells, but the purpose of α-tryptase is enigmatic, because its tetramers lack protease activity, whereas β-tryptase tetramers are active proteases. The monogenic disorder called hereditary α-tryptasemia, due to increased α-tryptase gene copies and protein expression, presents with clinical features such as vibratory urticaria and dysautonomia. We show that heterotetramers composed of 2α- and 2β-tryptase protomers (α/β-tryptase) form naturally in individuals who express α-tryptase. α/β-Tryptase, but not homotetramer, activates protease-activated receptor-2 (PAR2), which is expressed on cell types such as smooth muscle, neurons, and endothelium. Also, only α/β-tryptase makes mast cells susceptible to vibration-triggered degranulation by cleaving the α subunit of the EGF-like module–containing mucin-like hormone receptor-like 2 (EMR2) mechanosensory receptor. Allosteric effects of α-tryptase protomers on neighboring β-tryptase protomers likely result in the novel substrate repertoire of α/β-tryptase tetramers that in turn cause some of the clinical features of hereditary α-tryptasemia and of other disorders involving mast cells.

Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX

2009 ◽  
Vol 419 (2) ◽  
pp. 419-425 ◽  
Author(s):  
Martina Takacova ◽  
Tereza Holotnakova ◽  
Jan Vondracek ◽  
Miroslav Machala ◽  
Katerina Pencikova ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Aryl Hydrocarbon Receptor ◽  
Transcriptional Activation ◽  
Hypoxia Inducible Factor ◽  
Carbonic Anhydrase Ix ◽  
Independent Manner ◽  
Hypoxic Induction ◽  
Aryl Hydrocarbon ◽  
Ca Ix ◽  
Tcdd Treatment

Tumour-associated expression of CA IX (carbonic anhydrase IX) is to a major extent regulated by HIF-1 (hypoxia-inducible factor-1) which is important for transcriptional activation and consists of the oxygen-regulated subunit HIF-1α and the partner factor ARNT [AhR (aryl hydrocarbon receptor) nuclear translocator]. We have previously observed that HIF-1α competes with the AhR for interaction with ARNT under conditions when both conditionally regulated factors are activated. We have therefore investigated whether TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)-induced activation of the AhR pathway might interfere with CA IX expression. The results from the present study suggest that TCDD treatment reduces hypoxic induction of both CA IX mRNA and protein expression. Moreover, the transcriptional activity of the CA9 promoter was significantly reduced by expression of CAAhR (constitutively active AhR), which activates transcription in a ligand-independent manner. Finally, we found that ARNT is critical for both hypoxic induction and the TCDD-mediated inhibition of CA9 expression.

scholarly journals Induction of Proteases in Peritoneal Carcinomatosis, the Role of ICAM-1/CD43 Interaction

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Nawar A. Alkhamesi ◽  
Gretta Roberts ◽  
Paul Ziprin ◽  
David H. Peck ◽  
Ara W. Darzi
Keyword(s):  
Tumor Cells ◽  
Tumor Invasion ◽  
Direct Contact ◽  
Therapeutic Option ◽  
Gelatin Zymography ◽  
Cell Types ◽  
Vital Role ◽  
Indirect Contact ◽  
Clinical Issue

Introduction The development of peritoneal metastases is a significant clinical issue in the treatment of abdominal cancers and is associated with poor prognosis. We have previously shown that ICAM-1-CD43 interaction plays a significant role in tumor adhesion. However, an invasive phenotype is critical to establish tumor progression via cell associated and secreted proteases including matrix metalloproteinases. High metalloproteinases level significantly enhanced metastasis phenotype on tumors, a detrimental effect on surgical outcome. We investigated the role of direct and indirect signaling between the mesothelium and the tumor cells in enhancing tumor invasion and possible therapeutic intervention. Methods Mesothelial cells were enzymatically derived from human omental tissue and implanted in 24 wells plates. Colorectal cancer cells were then introduced and allowed a direct and an indirect contact with the mesothelial layer. Anti-ICAM antibodies, anti-CD43 antibodies, and heparin were used to block MMP production. Gelatin zymography was performed on the supernatant to detect MMPs activity. Results MMP production was observed in mesothelial and tumor cells. Direct contact between cell types enhanced MMP9 and 2 (p < 0.05). Indirect contact also stimulate MMPs but at a lower degree. ICAM-1 blocking antibodies attenuated MMP production in direct contact to that observed in the indirect. Heparin introduction achieved a similar outcome. Conclusions ICAM-1-CD43 interaction plays a vital role in tumor cells-peritoneum adhesion and invasion, which is manifested by the increased production of MMPs leading to tumor invasion and peritoneal loco-regional. Blocking this interaction with heparin can provide a new therapeutic option.

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