scholarly journals Pathophysiological Effects of Overactive STIM1 on Murine Muscle Function and Structure

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1730
Author(s):  
Roberto Silva-Rojas ◽  
Anne-Laure Charles ◽  
Sarah Djeddi ◽  
Bernard Geny ◽  
Jocelyn Laporte ◽  
...  
Keyword(s):  
Muscle Function ◽  
Expression Profiles ◽  
Mitochondrial Activity ◽  
Key Factors ◽  
Aberrant Expression ◽  
Functional Studies ◽  
Cellular Processes ◽  
Disease Signature ◽  
Contraction And Relaxation

Store-operated Ca2+ entry (SOCE) is a ubiquitous mechanism regulating extracellular Ca2+ entry to control a multitude of Ca2+-dependent signaling pathways and cellular processes. SOCE relies on the concerted activity of the reticular Ca2+ sensor STIM1 and the plasma membrane Ca2+ channel ORAI1, and dysfunctions of these key factors result in human pathologies. STIM1 and ORAI1 gain-of-function (GoF) mutations induce excessive Ca2+ influx through SOCE over-activation, and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two overlapping disorders characterized by muscle weakness, and additional multi-systemic signs affecting growth, platelets, spleen, skin, and intellectual abilities. In order to investigate the pathophysiological effect of overactive SOCE on muscle function and structure, we combined transcriptomics with morphological and functional studies on a TAM/STRMK mouse model. Muscles from Stim1R304W/+ mice displayed aberrant expression profiles of genes implicated in Ca2+ handling and excitation-contraction coupling (ECC), and in vivo investigations evidenced delayed muscle contraction and relaxation kinetics. We also identified signs of reticular stress and abnormal mitochondrial activity, and histological and respirometric analyses on muscle samples revealed enhanced myofiber degeneration associated with reduced mitochondrial respiration. Taken together, we uncovered a molecular disease signature and deciphered the pathomechanism underlying the functional and structural muscle anomalies characterizing TAM/STRMK.

MicroRNA Expression and Regulation of Hematopoiesis in CD34+ Cells: A Bioinformatic Circuit Diagram of the Hematopoietic Differentiation Control.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1334-1334
Author(s):  
Robert W. Georgantas ◽  
Richard Hildreth ◽  
Jonathan Alder ◽  
Carlo M. Croce ◽  
George A. Calin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Expression Profiles ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Hematopoietic Differentiation ◽  
Aberrant Expression ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract MicroRNAs (miRs) are a recently realized class of epigenetic elements which block translation of mRNA to protein. MicroRNAs have been shown to control cellular metabolism, apoptosis, differentiation and development in numerous organisms including drosophila, rat, mouse, and humans. Recently, miRs have been implicated in the control of hematopoiesis. Importantly, both aberrant expression and deletion of miRs are have been associated with the development of various cancers. In a previous study, we determined the gene expression profiles of HSC-enriched, HPC-enriched, and total CD34+ cells from human PBSC, BM, and CB. One rather surprising finding from this study was that virtually all of “hematopoietic important” genes were expressed at virtually identical levels within all populations examined. One of our hypotheses to explain this phenomena was that miRs may control differentiation by controlling protein expression from these “hematopoietic” RNAs. To examine the possible role of miRs in normal hematopoiesis and their relation to the HSPC transcriptome, we used mir-miroarrays to determine the miR expression profile of primary normal human mobilized blood and bone marrow CD34+ hematopoietic stem-progenitor cells (HSPCs). We have combined this miR data with (1) our extensive mRNA expression data obtained previously for CD34+ HSPCs, CD34+/CD38−/Lin- stem cell-enriched, CD34+/CD38+/Lin+ progenitor-enriched populations, and total CD34+ HSPC (Georgantas, Cancer Research 64:4434) and (2) miR target predictions from various published algorithms. Combining these datasets into one integrated database allowed us to bioinformaticly examine the global interaction of HSPC mRNAs and miRs during hematopoiesis. The 3′UTR sequences from many of these “hematopoietic” mRNA were cloned behind a luciferase reporter. K562 cells were transfected with these luc-3′UTR constructs, confirmating that expression of many important hematopoietic proteins are controlled by miRs. Based on our bioinformatic and protein expression studies, we present a global in silico model by which microRNAs control and direct hematopoietic differentiation. Actual in vitro and in vivo studies addressing the action of specific miRs in hematopoietic differentiation are presented in separate abstracts.

scholarly journals Use of Imaging to Assess Normal and Adaptive Muscle Function

2007 ◽  
Vol 87 (6) ◽  
pp. 704-718 ◽  
Author(s):  
Richard L Segal
Keyword(s):  
Mr Imaging ◽  
Muscle Function ◽  
Phase Contrast ◽  
Physical Therapists ◽  
Mr Elastography ◽  
Cellular Processes ◽  
Medical Centers ◽  
Therapeutic Measures ◽  
Cine Phase Contrast

Physical therapists must be able to determine the activity and passive properties of the musculoskeletal system in order to accurately plan and evaluate therapeutic measures. Discussed in this article are imaging methods that not only allow for the measurement of muscle activity but also allow for the measurement of cellular processes and passive mechanical properties noninvasively and in vivo. The techniques reviewed are T1- and T2-weighted magnetic resonance (MR) imaging, MR spectroscopy, cine–phase-contrast MR imaging, MR elastography, and ultrasonography. At present, many of these approaches are expensive and not readily available in physical therapy clinics but can be found at medical centers. However, there are ways of using these techniques to provide important knowledge about muscle function. This article proposes creative ways in which to use these techniques as evaluative tools.

scholarly journals Elevated Expression of The Rhythm Gene NFIL3 Promotes The Progression of TNBC By Activating NF-κB Signaling Through Suppression of NFKBIA Transcription

2021 ◽  
Author(s):  
Wei-Wei Yang ◽  
Jing Li ◽  
Minghui Zhang ◽  
Haichuan Yu ◽  
Yuan Zhuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epidemiological Studies ◽  
Tumor Formation ◽  
Cell Counting ◽  
Aberrant Expression ◽  
Functional Studies ◽  
Proliferation And Metastasis

Abstract Background: Epidemiological studies have confirmed that abnormal circadian rhythms are associated with tumorigenesis in breast cancer. However, few studies have investigated the pathological roles of rhythm genes in breast cancer progression. Methods: The expressions of NFIL3 and NFKBIA were measured by Western blot, qRT–PCR and IHC analysis. The proliferation and metastasis of two TNBC cell lines were analyzed by cell counting assays, clone formation assays, subcutaneous tumor formation assay, wound healing assays, transwell assays and the mouse tail vein injection model.Results: We evaluated the aberrant expression of 32 rhythm genes in breast cancer and identified that nuclear factor interleukin 3 regulated (NFIL3) expression is significantly altered in triple-negative breast cancer (TNBC). We found that NFIL3 inhibits its own transcription, and thus, downregulated NFIL3 mRNA indicates high expression of NFIL3 protein in breast cancer. Functional studies demonstrated that NFIL3 promotes the proliferation and metastasis of TNBC cells in vitro and in vivo. Higher expression of NFIL3 is associated with poor prognosis of patients with TNBC. Gene enrichment assays revealed that NFIL3 primarily regulates cancer-associated inflammation. Correlation analysis showed that expression of NFIL3 is associated with infiltration level of various immune cells in breast cancer. We further demonstrated that NFIL3 enhances the activity of NF-κB signaling. Mechanistically, we revealed that NFIL3 directly suppresses the transcription of NFKBIA, which blocks the activation of NF-κB and inhibits the progression of TNBC cells in vitro and in vivo. Moreover, we showed that enhancing NF-κB activity by repressing NFKBIA largely mimics the oncogenic effect of NFIL3 in TNBC, and anti-inflammatory strategies targeting NF-κB activity block the oncogenic roles of NFIL3 in TNBC. Conclusion:NFIL3 promotes the progression of TNBC by suppressing NFKBIA and then enhancing NF-κB signaling-mediated cancer-associated inflammation. This study may provide a new target for TNBC prevention and therapy.

scholarly journals Comparative Transcriptomic and Metagenomic Analysis Reveal the Key Factors on the Growth Rate in Red Swamp Crayfish (Procambarus Clarkii)

2021 ◽  
Author(s):  
Duanduan Chen ◽  
Leifeng Guo ◽  
Hui Wang
Keyword(s):  
Procambarus Clarkii ◽  
Expression Profiles ◽  
Rapid Development ◽  
Key Factors ◽  
Kegg Database ◽  
Gut Flora ◽  
Important Species ◽  
Red Swamp Crayfish ◽  
Potential Impact

Abstract Background: Although red swamp crayfish (Procambarus clarkii) is one of the most important species in aquaculture, the factors that influence differences in growth and development between individual siblings are still not fully understood. To address this lack of knowledge, we designed experiments to elucidate factors contributing to individual differences by comparing the hepatopancreatic transcriptome and gut flora structure of individuals with differences in sibling crayfish size under the same rearing conditions and attempted to find links between gut flora and host transcriptome information. Result: In total, 300691028 high-quality reads were obtained that were used to assemble 60637958 unigenes. Comparison of the expression profiles of the hepatopancreas of crayfish of different sizes revealed 497 differentially expressed genes (P<0.05). A total of 32 KEGG signaling pathways were found to be enriched after the KEGG database and GO functional annotation analyses, with the highest number of unigene enrichments related to organismal metabolism. Additionally, we found that proteobacteria, tenericutes, actinobacteria, and bacteroidetes made up a larger portion of the microbiome of larger individuals, suggesting that crayfish microbiota adapts to rapid growth, which may promote accelerated development by regulating the expression level of relevant genes.Conclusions: This work has accumulated data to support the potential impact of structural alterations in gut flora under equivalent feeding conditions in explaining the differential expression of transcriptomic genes among differentially developing individuals of sibling crayfish. These results further elucidate how the intestinal environment affects the rapid development of invertebrate crustaceans and provide a reference for further understanding of the regulatory mechanisms of the host's in vivo environment.

scholarly journals Endogenous TDP-43 prevents retrotransposons activation through Dicer-2 activity and the RNA silencing machinery in Drosophila neurons

2019 ◽  
Author(s):  
Giulia Romano ◽  
Raffaella Klima ◽  
Fabian Feiguin
Keyword(s):  
Rna Binding ◽  
Expression Profiles ◽  
Physiological Role ◽  
Gene Expression Profiles ◽  
Genetic Rescue ◽  
Aberrant Expression ◽  
Genome Wide ◽  
Interfering Rna ◽  
Sirna Pathway

ABSTRACTThe aberrant expression of retrotransposable elements (RTEs) was observed in different neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a terminal disorder characterized by functional alterations in the small RNA-binding protein TDP-43, suggesting that these events might be connected. Using genome wide gene expression profiles, we detected RTEs highly upregulated in TDP-43-null Drosophila heads while, the genetic rescue of TDP-43 function reverted these modifications. Furthermore, we found that TDP-43 modulates the small interfering RNA (siRNA) silencing machinery responsible for RTEs repression. Molecularly, we observed that TDP-43 regulates the expression levels of Dicer-2 by direct protein-mRNA interactionsin vivo. Accordingly, the genetic or pharmacological recovery of Dicer-2 activity was sufficient to repress retrotransposons activation and revert the neurodegeneration in TDP-43-null Drosophila motoneurons. Our results, describe a novel physiological role of endogenous TDP-43 in the prevention of RTEs-induced neurodegeneration through the modulation of Dicer-2 activity and the siRNA pathway.

scholarly journals Upregulation of MicroRNA 18b Contributes to the Development of Colorectal Cancer by Inhibiting CDKN2B

2017 ◽  
Vol 37 (22) ◽  
Author(s):  
Yiming Li ◽  
Meng Chen ◽  
Juan Liu ◽  
Lianyun Li ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle Progression ◽  
Expression Profiles ◽  
Linear Regression Analysis ◽  
Ectopic Expression ◽  
Multiple Linear Regression Analysis ◽  
Luciferase Assay ◽  
Aberrant Expression

ABSTRACT MicroRNAs (miRNAs) exhibit aberrant expression in the initiation and progression of a variety of human cancers, including colorectal cancer (CRC). However, the exact mechanisms are not well defined. miRNA expression profiles were characterized by microarrays in CRC samples, and miRNA 18b (miR-18b) was increased significantly in tumor tissues. The expression of miR-18b was confirmed in the CRC cell lines SW480 and HCT116 and 44 clinical specimens by quantitative real-time PCR (qRT-PCR). Multiple linear regression analysis showed a strong correlation of miR-18b expression with lymph node and distant metastasis. Overexpression of miR-18b promoted cell proliferation by facilitating cell cycle progression, and knockdown of miR-18b significantly suppressed migration in CRC cells. CDKN2B was identified as a target of miR-18b by high-throughput RNA sequencing and bioinformatics. After transfection with a miR-18b mimic, expression of CDKN2B was reduced significantly in CRC cells, and the effect was restored when a miR-18b inhibitor was transfected. A luciferase assay indicated miR-18b directly binds to the 3′ untranslated region (UTR) of CDKN2B. Expression of CDKN2B was downregulated in patient cancer tissues and negatively correlated with miR-18b. In a model of ectopic expression of miR-18b and CDKN2B, CDKN2B overexpression antagonized the effects of miR-18b in vitro and in vivo. The data show that miR-18b is involved in CRC carcinogenesis through targeting CDKN2B.

scholarly journals LncRNA RP11-79H23.3 Functions as a Competing Endogenous RNA to Regulate PTEN Expression through Sponging hsa-miR-107 in the Development of Bladder Cancer

2018 ◽  
Vol 19 (9) ◽  
pp. 2531 ◽  
Author(s):  
Hong Chi ◽  
Rui Yang ◽  
Xiaying Zheng ◽  
Luyu Zhang ◽  
Rong Jiang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Cycle Progression ◽  
Expression Profiles ◽  
Clinical Stage ◽  
Suppressive Effect ◽  
Pten Expression ◽  
Aberrant Expression ◽  
Tensin Homolog

Accumulating evidence indicates that the aberrant expression of long noncoding RNAs (lncRNAs) is involved in tumorigenesis and cancer development. However, the biological functions and underlying mechanisms of lncRNAs in bladder cancer (BC) remain largely unknown. Here, we analyzed the lncRNA and mRNA expression profiles in BC using a microarray assay. We found that lncRNA RP11-79H23.3 and phosphatase and tensin homolog (PTEN) were significantly downregulated in BC tissues and cells. Meanwhile, RP11-79H23.3 expression was negatively correlated with clinical stage in BC. Functionally, we found that overexpression of RP11-79H23.3 could suppress cell proliferation, migration, and cell cycle progression, rearrange the cytoskeleton, and induce apoptosis in vitro. Moreover, upregulation of RP11-79H23.3 inhibited the angiogenesis, tumorigenesis, and lung metastasis in vivo, whereas RP11-79H23.3 knockdown exerted a contrary role. Mechanistically, we identified that RP11-79H23.3 could directly bind to miR-107 and abolish the suppressive effect on target gene PTEN, which leads to inactivation of the PI3K/Akt signaling pathway. Taken together, we first demonstrated that RP11-79H23.3 might suppress the pathogenesis and development of BC by acting as a sponge for miR-107 to increase PTEN expression. Our research revealed that RP11-79H23.3 could be a potential target for diagnosis and therapy of BC.

Prognostic Role of Hedgehog-GLI1 Signaling Pathway in Aggressive and Metastatic Breast Cancers

2020 ◽  
Vol 21 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Prasuja Rokkam ◽  
Shailender Gugalavath ◽  
Deepak Kakara Gift Kumar ◽  
Rahul Kumar Vempati ◽  
Rama Rao Malla
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Neural Development ◽  
Splice Variants ◽  
Metastatic Breast ◽  
Basic Function ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Aberrant Expression ◽  
Cellular Processes

Glioma-associated oncogene homolog 1 (GLI1) is reported as an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human. The GLI1 gene was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a region of 5’ and 3’- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also regulates tumor tolerance, chemoresistance, and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients. GLI1 is an essential mediator of the SHH signaling pathway regulating self-renewal of stem cells, angiogenesis, and expression of FOXS1, CYR61. GLI1 mediated HH pathway can induce apoptosis. Hence, GLI1 can be a future diagnostic, prognostic marker, and as well as a potent target of therapeutics in breast cancer.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

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