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Total 58 results found since Jan 2013.

SLN124, a Galnac-siRNA Conjugate Targeting TMPRSS6, for the Treatment of Iron Overload and Ineffective Erythropoiesis Such As in Beta-Thalassemia
Accumulation of excess iron in tissues causes organ damage and dysfunction and may lead to serious clinical consequences including liver cirrhosis, diabetes, growth retardation and heart failure. Iron overload is a major health threat in iron loading anemias, like beta-thalassemia, myelodysplastic syndrome and in hereditary hemochromatosis. In patients with beta-thalassemia major, iron overload develops due to frequent blood transfusions to control the severe anemia. In addition, iron overload also occurs in patients with beta thalassemia intermedia (non-transfusion dependent beta-thalassemia). In the later cases, iron ove...
Source: Blood - November 21, 2018 Category: Hematology Authors: Altamura, S., Altamura, S., Muckenthaler, M. U., Dames, S., Frauendorf, C., Schubert, S., Aleku, M., Vadolas, J., Grigoriadis, G., Zugel, U. Tags: 102. Regulation of Iron Metabolism: Poster II Source Type: research

TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter
Discussion Dynamic changes in the functional phenotype of macrophages are associated with pathogenesis of inflammatory diseases (5–7). TonEBP primes macrophages toward an M1 phenotype, which has pro-inflammatory properties. TonEBP does this by promoting expression of pro-inflammatory genes via interaction with NF-κB (36) and by binding directly to the promoter (37, 64). In addition, TonEBP suppresses expression of the anti-inflammatory cytokine IL-10 by limiting chromatin access to the promoter (37). The pro-inflammatory function of TonEBP suggests that inhibiting its expression or activation could suppres...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research

High-Throughput Characterization of Viral and Cellular Protein Expression Patterns During JC Polyomavirus Infection
Discussion The study of viral infections in vitro has provided innumerable advances to the field of virology. However, the lack of rapid and efficient screening tools has hindered research progress for some viruses, like JCPyV (Houff et al., 1983; Zu Rhein, 1983; Assetta and Atwood, 2017). To overcome this challenge, the development of high-throughput analyses is needed to help aid in the production of large data sets and generation of multiple lines of inquiry. Current methodologies for analyzing JCPyV infectivity predominantly rely on manual quantitation of infection by indirect immunodetection of viral proteins by epif...
Source: Frontiers in Microbiology - April 16, 2019 Category: Microbiology Source Type: research

IFIT5 Participates in the Antiviral Mechanisms of Rainbow Trout Red Blood Cells
We described a new defense mechanism based on IFIT5 antiviral activity in nucleated RBCs that appeared to contribute to halting the VHSV infection. This finding sheds light into novel antiviral therapeutics to mitigate the economic losses and social impact caused by viral infections in the aquaculture industry. This work broadens the knowledge of fish nucleated RBCs functions and their role in the immune response to viral infections. Ethics Statement Experimental protocols and methods relating to experimental animals were reviewed and approved by the Animal Welfare Body and the Research Ethics Committee at the University...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

Role of Sirt3 in mitochondrial biogenesis and developmental competence of human in vitro matured oocytes
STUDY QUESTION Does Sirt3 dysfunction result in poor developmental outcomes for human oocytes after in vitro maturation (IVM)? SUMMARY ANSWER Inefficient Sirt3 expression induced decreased mitochondrial DNA copy number and biogenesis, and therefore impaired the developmental competence of human IVM oocytes. WHAT IS KNOWN ALREADY Cytoplasmic immaturity in IVM oocytes may lead to reduced developmental competence. Mitochondrial dysfunction results in the accumulation of free radicals and leads to DNA mutations, protein damage, telomere shortening and apoptosis. SIRT3 (in the Sirtuin protein family) has emerged as a mitochon...
Source: Human Reproduction - February 16, 2016 Category: Reproduction Medicine Authors: Zhao, H.-C., Ding, T., Ren, Y., Li, T.-J., Li, R., Fan, Y., Yan, J., Zhao, Y., Li, M., Yu, Y., Qiao, J. Tags: Reproductive biology Source Type: research

The Functions of Non-coding RNAs in rRNA Regulation
Qi Yan1, Chengming Zhu1, Shouhong Guang1,2* and Xuezhu Feng1* 1Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China 2CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Hefei, China Ribosomes are ribonucleoprotein machines that decode the genetic information embedded in mRNAs into polypeptides. Ribosome biogenesis is tightly coordinated and controlled from the transcription of pre-rRNAs to the assembly of ribosomes. Defects or disorders in rRNA production result in a number of human ri...
Source: Frontiers in Genetics - April 4, 2019 Category: Genetics & Stem Cells Source Type: research

Detailed Dissection of UBE3A-Mediated DDI1 Ubiquitination
Discussion Poly-ubiquitinated proteins targeted for degradation might be recognized directly by proteasomal receptors or by proteasomal shuttling proteins. The first shuttling proteins – Ddi1, Rad23 and Dsk2 – were identified and characterized in Saccharomyces cerevisiae (Lambertson et al., 1999; Kaplun et al., 2005). Proteasomal shuttles contain an N-terminal ubiquitin-like (UBL) domain that interacts with the 26S proteasome (Finley, 2009), and a C-terminal ubiquitin-binding domain domain (UBD) that binds to ubiquitin or poly-ubiquitin chains (Bertolaet et al., 2001). When ubiquitinated, substrates are capt...
Source: Frontiers in Physiology - May 2, 2019 Category: Physiology Source Type: research

The role of the osteopontin-integrin {alpha}v{beta}3 interaction at implantation: functional analysis using three different in vitro models
STUDY QUESTION Does the interaction between integrin and its ligand osteopontin (OPN) mediate embryonic attachment to endometrial epithelium at implantation? SUMMARY ANSWER OPN of epithelial origin binds the receptor integrin αvβ3 at the maternal surface to support adhesion during the early stages of implantation. WHAT IS KNOWN ALREADY Integrin αvβ3 and OPN are both present in the endometrial luminal epithelium in the mid-secretory phase. STUDY DESIGN, SIZE, DURATION Microscopy of attachment sites of blastocysts (mouse, n = 151, human, n = 8) and OPN- or BSA-coated beads (n = 488) interacting with ...
Source: Human Reproduction - March 11, 2014 Category: Reproduction Medicine Authors: Kang, Y.-J., Forbes, K., Carver, J., Aplin, J. D. Tags: Reproductive biology Source Type: research

NEDD8-mediated neddylation is required for human endometrial stromal proliferation and decidualization
STUDY QUESTION Does NEDD8-mediated neddylation regulate human endometrial stromal proliferation and decidualization? SUMMARY ANSWER Neddylation inhibition by a selective NEDD8-activating enzyme inhibitor, MLN4924, significantly impairs human endometrial stromal cell (HESC) proliferation and decidualization and facilitates cell senescence, via p21 accumulation. WHAT IS KNOWN ALREADY Neddylation regulates cell proliferation and tissue remodeling during embryogenesis and tumorigenesis, while human endometrial stroma undergoes sequential proliferation, differentiation, as well as dynamic tissue remodeling during each menstru...
Source: Human Reproduction - June 18, 2015 Category: Reproduction Medicine Authors: Liao, Y., Jiang, Y., He, H., Ni, H., Tu, Z., Zhang, S., Wang, B., Lou, J., Quan, S., Wang, H. Tags: Reproductive biology Source Type: research

Spindlin 1 is essential for metaphase II stage maintenance and chromosomal stability in porcine oocytes
This study is based on <span style="font-style:italic;">in vitro</span> investigations with abnormal expression levels of Spin1. This may or may not accurately reflect the situation <span style="font-style:italic;">in vivo</span>.<div class="boxTitle">Wider implications of the findings</div>Spin1 is essential to maintain MII arrest, but a high level of Spin1 induces DNA damage in oocytes and embryos. Thus, a system to accurately regulate Spin1 expression operates in porcine MII-stage oocytes and embryos.<div class="boxTitle">Study funding and competing interest(s)</div>This r...
Source: Molecular Human Reproduction - March 6, 2017 Category: Molecular Biology Source Type: research

Immune-Modulation by the Human Respiratory Syncytial Virus: Focus on Dendritic Cells
This study is complemented by another report that found that hRSV infection induces significant expression of three miRNAs, namely hsa-miR-4448, hsa-miR-30a-5p, and hsa-miR-4634 in human DCs (104). Interestingly, this latter study also performed comparative analyses of miRNA profiles between DCs infected with hRSV and a related virus, namely the human metapneumovirus, and found that both viruses induced the expression of elevated levels of hsa-miR-4634. Elucidating the contribution of these miRNAs in DCs in response to hRSV remains to be determined. Dendritic Cell Phenotype and Migration Upon hRSV Infection in vivo Altho...
Source: Frontiers in Immunology - April 14, 2019 Category: Allergy & Immunology Source Type: research

A Novel Regulator of Preadipocyte Differentiation, Transcription Factor TCF21, Functions Partially Through Promoting LPL Expression
Discussion Excessive fat deposition in chickens can result in many undesirable consequences within the poultry industry, including reduced feeding efficiency (Zhou et al., 2006) and decreased reproductive performance (Walzem and Chen, 2014). Thus, broiler breeders urgently require a more thorough understanding of the molecular mechanism governing chicken adipogenesis. We previously found that broilers from lean and fat lines exhibit clear differences in reproductive performance (Zhang et al., 2018). In addition, TCF21 was found to be related to testis growth and development in these broilers (Zhang et al., 2017). In mice ...
Source: Frontiers in Physiology - April 22, 2019 Category: Physiology Source Type: research

GnRH regulates trophoblast invasion via RUNX2-mediated MMP2/9 expression
STUDY HYPOTHESIS We hypothesized that Runt-related transcription factor 2 (RUNX2), matrix metalloproteinase (MMP)2 and MMP9 are involved in basal and gonadotrophin-releasing hormone (GnRH)-induced human extravillous trophoblast (EVT) cell invasion. STUDY FINDING Our finding indicates that GnRH-induced RUNX2 expression enhances the invasive capacity of EVT cells by modulating the expression of MMP2 and MMP9. WHAT IS KNOWN ALREADY GnRH is expressed in first-trimester placenta and exerts pro-invasive effects on EVT cells in vitro. RUNX2 regulates MMP2 and MMP9 expression and is often associated with invasive phenotypes. ST...
Source: Molecular Human Reproduction - January 30, 2016 Category: Molecular Biology Authors: Peng, B., Zhu, H., Klausen, C., Ma, L., Wang, Y.-l., Leung, P. C. K. Tags: Articles Source Type: research

Overexpression of chloride channel-3 is associated with the increased migration and invasion ability of ectopic endometrial cells from patients with endometriosis
STUDY QUESTION Is chloride channel-3 (ClC-3) involved in regulating the biological behavior of endometrial stromal cells (ESCs)? SUMMARY ANSWER ClC-3 promotes endometriotic cell migration and invasion. WHAT IS KNOWN ALREADY ClC-3 plays a significant role in the migration and invasion of various kinds of cells. STUDY DESIGN, SIZE, DURATION An in vitro investigation of the effect of ClC-3 on the migration and invasion of ectopic ESCs from patients with endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS The ectopic and eutopic endometrial samples from 43 female patients with endometriosis and the endometrial samples ...
Source: Human Reproduction - April 20, 2016 Category: Reproduction Medicine Authors: Guan, Y.-t., Huang, Y.-q., Wu, J.-b., Deng, Z.-q., Wang, Y., Lai, Z.-y., Wang, H.-b., Sun, X.-x., Zhu, Y.-l., Du, M.-m., Zhu, L.-y., Chen, L.-x., Wang, L.-w. Tags: Gynaecology Source Type: research