Idiopathic gastroparesis is associated with specific transcriptional changes in the gastric muscularis externa

: Breast cancer (BC) is a multifactorial disease and becoming a major health issue in women throughout the globe. BC is a malignant type of cancer which results from transcriptional changes in proteins and genes. Besides the availability of modern medicines and detection tools, BC has become a topmost deadly disease and its cure still remains challenging. Nanotechnology based approaches are being employed for the diagnosis and treatment of BC at clinical stages. Nanosystems have a significant role in the study of the interaction of malignant cells with their microenvironment through receptor-based targeted approach. Nowadays, lipid-based nanocarriers are being popularized in the domain of pharmaceutical and medical biology for cancer therapy. Lipidic nanoparticlized systems (LNPs) have proven to have high loading efficiency, less toxicity, improved therapeutic efficacy, enhanced bioavailability and stability of the bioactive compounds compared to traditional drug delivery systems. In the present context, several LNPs based formulations have been undertaken in various phases of clinical trials in different countries. This review highlights the importance of chemotherapeutics based lipidic nanocarriers and their anticipated use for the treatment of BC. Furthermore, the clinical trials and future prospective of LNPs have been widely elaborated.

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Transcriptional landscape of PTEN loss in primary prostate cancer

BMC Cancer ◽

10.1186/s12885-021-08593-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Eddie Luidy Imada ◽

Diego Fernando Sanchez ◽

Wikum Dinalankara ◽

Thiago Vidotto ◽

Ericka M. Ebot ◽

...

Keyword(s):

Prostate Cancer ◽

Meta Analysis ◽

Pten Loss ◽

Primary Prostate Cancer ◽

Expression Atlas ◽

Transcriptomic Signature ◽

Transcriptional Changes ◽

New Biomarkers ◽

Adaptive Immune Systems ◽

Transcriptional Landscape

Abstract Background PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. In this study, we highlight the transcriptional changes associated with PTEN loss in PCa. Methods Using a meta-analysis approach, we leveraged two large PCa cohorts with experimentally validated PTEN and ERG status by Immunohistochemistry (IHC), to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. This signature was expanded to lncRNAs using the TCGA quantifications from the FC-R2 expression atlas. Results The signatures indicate a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. Highlighting potential novel lncRNAs associated with PTEN loss and PCa progression. Conclusion We created a PCa specific signature of the transcriptional landscape of PTEN loss that comprises both the coding and an extensive non-coding counterpart, highlighting potential new players in PCa progression. We also show that contrary to what is observed in other cancers, PTEN loss in PCa leads to increased activation of the immune system. These findings can help the development of new biomarkers and help guide therapy choices.

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Microarray analysis reveals an inflammatory transcriptomic signature in peripheral blood for sciatica

BMC Neurology ◽

10.1186/s12883-021-02078-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yi Wang ◽

Guogang Dai ◽

Ling Jiang ◽

Shichuan Liao ◽

Jiao Xia

Keyword(s):

Functional Analysis ◽

Network Analysis ◽

Peripheral Blood ◽

Differentially Expressed ◽

Healthy Controls ◽

Toll Like Receptor ◽

Qrt Pcr ◽

Transcriptomic Signature ◽

Transcriptional Changes ◽

Key Genes

Abstract Background Although the pathology of sciatica has been studied extensively, the transcriptional changes in the peripheral blood caused by sciatica have not been characterized. This study aimed to characterize the peripheral blood transcriptomic signature for sciatica. Methods We used a microarray to identify differentially expressed genes in the peripheral blood of patients with sciatica compared with that of healthy controls, performed a functional analysis to reveal the peripheral blood transcriptomic signature for sciatica, and conducted a network analysis to identify key genes that contribute to the observed transcriptional changes. The expression levels of these key genes were assessed by qRT-PCR. Results We found that 153 genes were differentially expressed in the peripheral blood of patients with sciatica compared with that of healthy controls, and 131 and 22 of these were upregulated and downregulated, respectively. A functional analysis revealed that these differentially expressed genes (DEGs) were strongly enriched for the inflammatory response or immunity. The network analysis revealed that a group of genes, most of which are related to the inflammatory response, played a key role in the dysregulation of these DEGs. These key genes are Toll-like receptor 4, matrix metallopeptidase 9, myeloperoxidase, cathelicidin antimicrobial peptide, resistin and Toll-like receptor 5, and a qRT-PCR analysis validated the higher transcript levels of these key genes in the peripheral blood of patients with sciatica than in that of healthy controls. Conclusion We revealed inflammatory characteristics that serve as a peripheral blood transcriptomic signature for sciatica and identified genes that are essential for mRNA dysregulation in the peripheral blood of patients with sciatica.

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Single-Cell Transcriptional Heterogeneity of Lymphatic Endothelial Cells in Normal and Inflamed Murine Lymph Nodes

Cells ◽

10.3390/cells10061371 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1371

Author(s):

Eliane Sibler ◽

Yuliang He ◽

Luca Ducoli ◽

Nadja Keller ◽

Noriki Fujimoto ◽

...

Keyword(s):

Endothelial Cells ◽

Lymph Nodes ◽

Single Cell ◽

In Silico Analysis ◽

Skin Inflammation ◽

Lymphatic Endothelial Cells ◽

Depth Analysis ◽

Subcapsular Sinus ◽

Transcriptional Changes ◽

Sinus Floor

The lymphatic system plays a crucial role in immunity and lymph nodes (LNs) undergo drastic remodeling during inflammation. Here, we used single-cell RNA sequencing to investigate transcriptional changes in lymphatic endothelial cells (LECs) in LNs draining naïve and inflamed skin. We found that subsets of LECs lining the different LN sinuses responded individually to skin inflammation, suggesting that they exert distinct functions under pathological conditions. Among the genes dysregulated during inflammation, we confirmed an up-regulation of CD200 in the LECs lining the subcapsular sinus floor with a possible function in immune regulation. Furthermore, by in silico analysis, we predicted numerous possible interactions of LECs with diverse immune cells in the LNs and found similarities in the transcriptional changes of LN LECs in different skin inflammation settings. In summary, we provide an in-depth analysis of the transcriptional landscape of LN LECs in the naïve state and in skin inflammation.

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High-throughput transcriptomic analysis of human primary hepatocyte spheroids exposed to per- and polyfluoroalkyl substances (PFAS) as a platform for relative potency characterization

Toxicological Sciences ◽

10.1093/toxsci/kfab039 ◽

2021 ◽

Author(s):

A Rowan-Carroll ◽

A Reardon ◽

K Leingartner ◽

R Gagné ◽

A Williams ◽

...

Keyword(s):

Gene Expression ◽

Cholesterol Biosynthesis ◽

Health Hazard ◽

Biological Responses ◽

Similar Gene Expression Profile ◽

Transcriptional Changes ◽

Hazard And Risk ◽

Hepatocyte Spheroids ◽

Similar Gene ◽

Identify Gene Expression

Abstract Per- and poly-fluoroalkyl substances (PFAS) are widely found in the environment because of their extensive use and persistence. Although several PFAS are well studied, most lack toxicity data to inform human health hazard and risk assessment. This study focussed on four model PFAS: perfluorooctanoic acid (PFOA; 8 carbon), perfluorobutane sulfonate (PFBS; 4 carbon), perfluorooctane sulfonate (PFOS; 8 carbon), and perfluorodecane sulfonate (PFDS; 10 carbon). Human primary liver cell spheroids (pooled from 10 donors) were exposed to 10 concentrations of each PFAS and analyzed at four time-points. The approach aimed to: (1) identify gene expression changes mediated by the PFAS; (2) identify similarities in biological responses; (3) compare PFAS potency through benchmark concentration analysis; and (4) derive bioactivity exposure ratios (ratio of the concentration at which biological responses occur, relative to daily human exposure). All PFAS induced transcriptional changes in cholesterol biosynthesis and lipid metabolism pathways, and predicted PPARα activation. PFOS exhibited the most transcriptional activity and had a highly similar gene expression profile to PFDS. PFBS induced the least transcriptional changes and the highest benchmark concentration (i.e., was the least potent). The data indicate that these PFAS may have common molecular targets and toxicities, but that PFOS and PFDS are the most similar. The transcriptomic bioactivity exposure ratios derived here for PFOA and PFOS were comparable to those derived using rodent apical endpoints in risk assessments. These data provide a baseline level of toxicity for comparison with other known PFAS using this testing strategy.

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Distinct regulation of hippocampal neuroplasticity and ciliary genes by corticosteroid receptors

Nature Communications ◽

10.1038/s41467-021-24967-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Karen R. Mifsud ◽

Clare L. M. Kennedy ◽

Silvia Salatino ◽

Eshita Sharma ◽

Emily M. Price ◽

...

Keyword(s):

Dna Sequences ◽

Glucocorticoid Receptors ◽

Acute Stress ◽

Circadian Variation ◽

Rna Seq ◽

Physiological Regulation ◽

Behavioural Adaptation ◽

Neuronal Progenitor ◽

Genome Wide ◽

Transcriptional Changes

AbstractGlucocorticoid hormones (GCs) — acting through hippocampal mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) — are critical to physiological regulation and behavioural adaptation. We conducted genome-wide MR and GR ChIP-seq and Ribo-Zero RNA-seq studies on rat hippocampus to elucidate MR- and GR-regulated genes under circadian variation or acute stress. In a subset of genes, these physiological conditions resulted in enhanced MR and/or GR binding to DNA sequences and associated transcriptional changes. Binding of MR at a substantial number of sites however remained unchanged. MR and GR binding occur at overlapping as well as distinct loci. Moreover, although the GC response element (GRE) was the predominant motif, the transcription factor recognition site composition within MR and GR binding peaks show marked differences. Pathway analysis uncovered that MR and GR regulate a substantial number of genes involved in synaptic/neuro-plasticity, cell morphology and development, behavior, and neuropsychiatric disorders. We find that MR, not GR, is the predominant receptor binding to >50 ciliary genes; and that MR function is linked to neuronal differentiation and ciliogenesis in human fetal neuronal progenitor cells. These results show that hippocampal MRs and GRs constitutively and dynamically regulate genomic activities underpinning neuronal plasticity and behavioral adaptation to changing environments.

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