CIMB, Vol. 46, Pages 3551-3562: Multi-Omics Integration for Liver #cancer Using Regression Analysis

Genetic biomarkers have played a pivotal role in the classification, prognostication, and guidance of clinical #cancer therapies. Large-scale and multi-dimensional analyses of entire #cancer genomes, as exemplified by projects like The #cancer Genome Atlas (TCGA), have yielded an extensive repository of data that holds the potential to unveil the underlying biology of these malignancies. Mutations stand out as the principal catalysts of cellular transformation. Nonetheless, other global genomic processes, such as alterations in gene expression and chromosomal re-arrangements, also play crucial roles in conferring cellular immortality. The incorporation of multi-omics data specific to #cancer has demonstrated the capacity to enhance our comprehension of the molecular mechanisms underpinning carcinogenesis. This report elucidates how the integration of comprehensive data on methylation, gene expression, and copy number variations can effectively facilitate the unsupervised clustering of #cancer samples. We have identified regressors that can effectively classify tumor and normal samples with an optimal integration of #RNA sequencing, DNA methylation, and copy number variation while also achieving significant p-values. Further, these regressors were trained using linear and logistic regression with k-means clustering. For comparison, we employed autoencoder- and stacking-based omics integration and computed silhouette scores to evaluate the clusters. The proof of concept is illustrated using liver #cancer data. Our analysis serves to underscore the feasibility of unsupervised #cancer classification by considering genetic markers beyond mutations, thereby emphasizing the clinical relevance of additional global cellular parameters that contribute to the transformative process in cells. This work is clinically relevant because changes in gene expression and genomic re-arrangements have been shown to be signatures of cellular transformation across #cancers, as well as in liver #cancers. https://www.mdpi.com/1467-3045/46/4/222?utm_source=dlvr.it&utm_medium=tumblr

Plants, Vol. 13, Pages 1137: Biological Activity of Artificial Plant Peptides Corresponding to the Translational Products of Small ORFs in Primary #miRNAs and Other Long “Non-Coding” #RNAs

Generally, lncPEPs (peptides encoded by long non-coding #RNAs) have been identified in many plant species of several families and in some animal species. Importantly, molecular mechanisms of the miPEPs (peptides encoded by primary micro#RNAs, pri-#miRNAs) are often poorly understood in different flowering plants. Requirement for the additional studies in these directions is highlighted by alternative findings concerning positive regulation of pri-#miRNA/#miRNA expression by synthetic miPEPs in plants. Further extensive studies are also needed to understand the full set of their roles in eukaryotic organisms. This review mainly aims to consider the available data on the regulatory functions of the synthetic miPEPs. Studies of chemically synthesized miPEPs and analyzing the fine molecular mechanisms of their functional activities are reviewed. Brief description of the studies to identify lncORFs (open reading frames of long non-coding #RNAs) and the encoded protein products is also provided. https://www.mdpi.com/2223-7747/13/8/1137?utm_source=dlvr.it&utm_medium=tumblr

#RNA's hidden potential: New study unveils its role in early life and future bioengineering

The beginning of life on Earth and its #evolution over billions of years continue to intrigue researchers worldwide. The central dogma or the directional flow of genetic information from a deoxyribose nucleic acid (DNA) template to a ribose nucleic acid (#RNA) transcript, and finally into a functional protein, is fundamental to cellular structure and functions. https://phys.org/news/2024-04-rna-hidden-potential-unveils-role.html?utm_source=dlvr.it&utm_medium=tumblr

#RNA's hidden potential: New study unveils its role in early life and future bioengineering

The beginning of life on Earth and its #evolution over billions of years continue to intrigue researchers worldwide. The central dogma or the directional flow of genetic information from a deoxyribose nucleic acid (DNA) template to a ribose nucleic acid (#RNA) transcript, and finally into a functional protein, is fundamental to cellular structure and functions. https://phys.org/news/2024-04-rna-hidden-potential-unveils-role.html?utm_source=dlvr.it&utm_medium=tumblr

Ranking of cell clusters in a single-cell #RNA-sequencing analysis framework using prior knowledge

by Anastasis Oulas, Kyriaki Savva, Nestoras Karathanasis, George M. Spyrou Prioritization or ranking of different cell types in a Single-cell #RNA Sequencing (sc#RNA-Seq) framework can be performed in a variety of ways, some of these include: i) obtaining an indication of the proportion of cell types between the different conditions under study, ii) counting the number of differentially expressed genes (DEGs) between cell types and conditions in the experiment or, iii) prioritizing cell types based on prior knowledge about the conditions under study (i.e., a specific disease). These methods have drawbacks and limitations thus novel methods for improving cell ranking are required. Here we present a novel methodology that exploits prior knowledge in combination with expert-user information to accentuate cell types from a sc#RNA-seq analysis that yield the most biologically meaningful results with respect to a disease under study. Our methodology allows for ranking and prioritization of cell-types based on how well their expression profiles relate to the molecular mechanisms and drugs associated with a disease. Molecular mechanisms, as well as drugs, are incorporated as prior knowledge in a standardized, structured manner. Cell-types are then ranked/prioritized based on how well results from data-driven analysis of sc#RNA-seq data match the predefined prior knowledge. In additional cell-cell communication perturbations between disease and control networks are used to further prioritize/rank cell-types. Our methodology has substantial advantages to more traditional cell ranking techniques and provides an informative complementary methodology that utilizes prior knowledge in a rapid and automated manner, that has previously not been attempted by other studies. The current methodology is also implemented as an R package entitled Single Cell Ranking Analysis Toolkit (scRANK) and is available for download and installation via GitHub (https://#hub.com/aoulas/scRANK) https://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1011550&utm_source=dlvr.it&utm_medium=tumblr

Toxics, Vol. 12, Pages 301: Oleanolic Acid Acetate Alleviates Cisplatin-Induced Nephrotoxicity via Inhibition of Apoptosis and Necroptosis In Vitro and In Vivo

Cisplatin is a widely used anti-#cancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas it increased Bcl-2 expression. Moreover, in a cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. #RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor-interacting protein kinase (RIPK) and mixed lineage kinase domain-like (MLKL) were identified. In an in vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted via co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anti-#cancer adjuvant. https://www.mdpi.com/2305-6304/12/4/301?utm_source=dlvr.it&utm_medium=tumblr

Cells, Vol. 13, Pages 703: Establishment and Characterization of SV40 T-Antigen Immortalized Porcine Muscle Satellite Cell

Muscle satellite cells (MuSCs) are crucial for muscle development and regeneration. The primary pig MuSCs (pMuSCs) is an ideal in vitro cell model for studying the pig’s muscle development and differentiation. However, the long-term in vitro culture of pMuSCs results in the gradual loss of their stemness, thereby limiting their application. To address this conundrum and maintain the normal function of pMuSCs during in vitro passaging, we generated an immortalized pMuSCs (SV40 T-pMuSCs) by stably expressing SV40 T-antigen (SV40 T) using a lentiviral-based vector system. The SV40 T-pMuSCs can be stably sub-cultured for over 40 generations in vitro. An evaluation of SV40 T-pMuSCs was conducted through immunofluorescence staining, quantitative real-time PCR, EdU assay, and SA-β-gal activity. Their proliferation capacity was similar to that of primary pMuSCs at passage 1, and while their differentiation potential was slightly decreased. Si#RNA-mediated interference of SV40 T-antigen expression restored the differentiation capability of SV40 T-pMuSCs. Taken together, our results provide a valuable tool for studying pig skeletal muscle development and differentiation. https://www.mdpi.com/2073-4409/13/8/703?utm_source=dlvr.it&utm_medium=tumblr

IJMS, Vol. 25, Pages 4469: Myeloid Cell-Derived IL-1 Signaling Damps Neuregulin-1 from Fibroblasts to Suppress Colitis-Induced Early Repair of the Intestinal Epithelium

Neuregulin-1 (Nrg1, gene symbol: Nrg1), a ligand of the ErbB receptor family, promotes intestinal epithelial cell proliferation and repair. However, the dynamics and accurate derivation of Nrg1 expression during colitis remain unclear. By analyzing the public single-cell #RNA-sequencing datasets and employing a dextran sulfate sodium (DSS)-induced colitis model, we investigated the cell source of Nrg1 expression and its potential regulator in the process of epithelial healing. Nrg1 was majorly expressed in stem-like fibroblasts arising early in mouse colon after DSS administration, and Nrg1–Erbb3 signaling was identified as a potential mediator of interaction between stem-like fibroblasts and colonic epithelial cells. During the ongoing colitis phase, a significant infiltration of macrophages and neutrophils secreting IL-1β emerged, accompanied by the rise in stem-like fibroblasts that co-expressed Nrg1 and IL-1 receptor 1. By stimulating intestinal or lung fibroblasts with IL-1β in the context of inflammation, we observed a downregulation of Nrg1 expression. Patients with inflammatory bowel disease also exhibited an increase in NRG1+IL1R1+ fibroblasts and an interaction of NRG1–ERBB between IL1R1+ fibroblasts and colonic epithelial cells. This study reveals a novel potential mechanism for mucosal healing after inflammation-induced epithelial injury, in which inflammatory myeloid cell-derived IL-1β suppresses the early regeneration of intestinal tissue by interfering with the secretion of reparative neuregulin-1 by stem-like fibroblasts. https://www.mdpi.com/1422-0067/25/8/4469?utm_source=dlvr.it&utm_medium=tumblr

Viruses, Vol. 16, Pages 631: Favipiravir Treatment Prolongs Survival in a Lethal BALB/c Mouse Model of Ebinur Lake Virus Infection

Orthobunyavirus is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored the antiviral effects of two broad-spectrum antiviral drugs, favipiravir and ribavirin, in a BALB/c mouse model. Favipiravir significantly improved the clinical symptoms of infected mice, reduced viral titer and #RNA copies in serum, and extended overall survival. The median survival times of mice in the vehicle- and favipiravir-treated groups were 5 and 7 days, respectively. Favipiravir significantly reduced virus titers 10- to 100-fold in sera at all three time points compared to vehicle-treated mice. And favipiravir treatment effectively reduced the virus copies by approximately 10-fold across the three time points, relative to vehicle-treated mice. The findings expand the antiviral spectrum of favipiravir for orthobunyaviruses in vivo. https://www.mdpi.com/1999-4915/16/4/631?utm_source=dlvr.it&utm_medium=tumblr

Animals, Vol. 14, Pages 1222: Elucidating the Role of Transcriptomic Networks and DNA Methylation in Collagen Deposition of Dezhou Donkey Skin

DNA methylation represents a predominant epigenetic modification with broad implications in various biological functions. Its role is particularly significant in the process of collagen deposition, a fundamental aspect of dermal development in donkeys. Despite its critical involvement, the mechanistic insights into how DNA methylation influences collagen deposition in donkey skin remain limited. In this study, we employed whole genome bisulfite sequencing (WGBS) and #RNA sequencing (#RNA-seq) to investigate the epigenetic landscape and gene expression profiles in the dorsal skin tissues of Dezhou donkeys across three developmental stages: embryonic (YD), juvenile (2-year-old, MD), and mature (8-year-old, OD). Our analysis identified numerous differentially methylated genes that play pivotal roles in skin collagen deposition and overall skin maturation, including but not limited to COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, GLUL, SFRP2, FOSL1, SERPINE1, MMP1, MMP2, MMP9, and MMP13. Notably, we observed an inverse relationship between gene expression and DNA methylation proximal to transcription start sites (TSSs), whereas a direct correlation was detected in regions close to transcription termination sites (TTSs). Detailed bisulfite sequencing analyses of the COL1A1 promoter region revealed a low methylation status during the embryonic stage, correlating with elevated transcriptional activity and gene expression levels. Collectively, our findings elucidate key genetic markers associated with collagen deposition in the skin of Dezhou donkeys, underscoring the significant regulatory role of DNA methylation. This research work contributes to the foundational knowledge necessary for the genetic improvement and selective breeding of Dezhou donkeys, aiming to enhance skin quality attributes. https://www.mdpi.com/2076-2615/14/8/1222?utm_source=dlvr.it&utm_medium=tumblr

Biosensors, Vol. 14, Pages 200: PCR Independent Strategy-Based Biosensors for #RNA Detection

#RNA is an important information and functional molecule. It can respond to the regulation of life processes and is also a key molecule in gene expression and regulation. Therefore, #RNA detection technology has been widely used in many fields, especially in disease diagnosis, medical research, genetic engineering and other fields. However, the current RT-qPCR for #RNA detection is complex, costly and requires the support of professional technicians, resulting in it not having great potential for rapid application in the field. PCR-free techniques are the most attractive alternative. They are a low-cost, simple operation method and do not require the support of large instruments, providing a new concept for the development of new #RNA detection methods. This article reviews current PCR-free methods, overviews reported #RNA biosensors based on electrochemistry, SPR, microfluidics, nanomaterials and CRISPR, and discusses their challenges and future research prospects in #RNA detection. https://www.mdpi.com/2079-6374/14/4/200?utm_source=dlvr.it&utm_medium=tumblr

Dentistry Journal, Vol. 12, Pages 113: Do Concurrent Peri-Implantitis and Periodontitis Share Their Microbiotas? A Pilot Study

The microbial compositions from concurrent peri-implant and periodontal lesions were compared, since the results reported in the literature on the etiological relationship between these oral pathologies are contradictory. Microbial compositions from nine patients were evaluated using Illumina MiSeq sequencing of 16S #rRNA gene amplicons and Principal Components Analysis. Comparisons between the use of curettes or paper points as collection methods and between bacterial composition in both pathologies were performed. Paper points allowed the recovery of a higher number of bacterial genera. A higher bacterial diversity was found in peri-implantitis compared to periodontal samples from the same patient, while a greater number of operational taxonomic units (OTUs) were present in the corresponding periodontal samples. A higher abundance of oral pathogens, such as Porphyromonas or Treponema, was found in peri-implantitis sites. The opposite trend was observed for Aggregatibacter abundance, which was higher in periodontal than in peri-implantitis lesions, suggesting that both oral pathologies could be considered different but related diseases. Although the analysis of a higher number of samples would be needed, the differences regarding the microbial composition provide a basis for further understating the pathogenesis of peri-implant infections. https://www.mdpi.com/2304-6767/12/4/113?utm_source=dlvr.it&utm_medium=tumblr

Plants, Vol. 13, Pages 1130: Fine Mapping of qAL5.2 Controlling Anther Length in Oryza sativa

Anther length is the critical floral trait determining hybrid rice seed production and is controlled by many quantitative trait loci (QTL). However, the cloning of genes specifically controlling anther size has yet to be reported. Here, we report the fine mapping of qAL5.2 for anther size using backcross inbred lines (BILs) in the genetic background of Oryza sativa indica Huazhan (HZ). Gene chip analysis on the BC4F2 and BC5F1 population identified effective loci on Chr1, Chr5, and Chr8 and two genomic regions on Chr5, named qAL5.1 and qAL5.2. qAL5.2 was identified in both populations with LOD values of 17.54 and 10.19, which explained 35.73% and 25.1% of the phenotypic variances, respectively. Ultimately qAL5.2 was localized to a 73 kb region between HK139 and HK140 on chromosome 5. And we constructed two near-isogenic lines (NILs) for #RNA-seq analysis, named NIL-qAL5.2HZ and NIL-qAL5.2KLY, respectively. The result of the GO enrichment analysis revealed that differential genes were significantly enriched in the carbohydrate metabolic process, extracellular region, and nucleic acid binding transcription, and KEGG enrichment analysis revealed that alpha-linolenic acid metabolism was significantly enriched. Meanwhile, candidate genes of qAL5.2 were analyzed in #RNA-seq, and it was found that ORF8 is differentially expressed between NIL-qAL5.2HZ and NIL-qAL5.2KLY. The fine mapping of qAL5.2 conferring anther length will promote the breed improvement of the restorer line and understanding of the mechanisms driving crop mating patterns. https://www.mdpi.com/2223-7747/13/8/1130?utm_source=dlvr.it&utm_medium=tumblr

Viruses, Vol. 16, Pages 626: Detection and Characterization of Influenza A Virus Endemic Circulation in Suckling and Nursery Pigs Originating from Vaccinated Farms in the Same Production System

Inactivated influenza A virus (IAV) vaccines help reduce clinical disease in suckling piglets, although endemic infections still exist. The objective of this study was to evaluate the detection of IAV in suckling and nursery piglets from IAV-vaccinated sows from farms with endemic IAV infections. Eight nasal swab collections were obtained from 135 two-week-old suckling piglets from four farms every other week from March to September 2013. Oral fluid samples were collected from the same group of nursery piglets. IAV #RNA was detected in 1.64% and 31.01% of individual nasal swabs and oral fluids, respectively. H1N2 was detected most often, with sporadic detection of H1N1 and H3N2. Whole-genome sequences of IAV isolated from suckling piglets revealed an H1 hemagglutinin (HA) from the 1B.2.2.2 clade and N2 neuraminidase (NA) from the 2002A clade. The internal gene constellation of the endemic H1N2 was TTTTPT with a pandemic lineage matrix. The HA gene had 97.59% and 97.52% nucleotide and amino acid identities, respectively, to the H1 1B.2.2.2 used in the farm-specific vaccine. A similar H1 1B.2.2.2 was detected in the downstream nursery. These data demonstrate the low frequency of IAV detection in suckling piglets and downstream nurseries from farms with endemic infections in spite of using farm-specific IAV vaccines in sows. https://www.mdpi.com/1999-4915/16/4/626?utm_source=dlvr.it&utm_medium=tumblr

TDEseq – temporal gene expression patterns from multi-sample multi-stage single-cell transcriptomics data

A new statistical method called TDEseq is poised to r#evolutionize the way we study temporal gene expression dynamics in single-cell #RNA sequencing (scRNA-seq) studies... https://www.rna-seqblog.com/tdeseq-temporal-gene-expression-patterns-from-multi-sample-multi-stage-single-cell-transcriptomics-data/?utm_source=dlvr.it&utm_medium=tumblr

Next-generation sequencing-based spatial transcriptomics: a perspective from barcoding chemistry

With recent advancements in barcoding and sequencing chemistry, scientists can now explore the spatial dimension of gene expression. By correlating transcripts... https://www.rna-seqblog.com/next-generation-sequencing-based-spatial-transcriptomics-a-perspective-from-barcoding-chemistry/?utm_source=dlvr.it&utm_medium=tumblr

MD Anderson and CureVac enter strategic collaboration to develop novel #cancer vaccines

Aligning complementary expertise, collaboration aims to develop off-the-shelf mRNA-based #cancer vaccines for select hematologic and solid #cancers The University of Texas MD Anderson #cancer Center and CureVac N.V. today announced a co-development and licensing agreement to develop novel mRNA-based #cancer vaccines. The collaboration creates strong synergies between CureVac’s unique end-to-end capabilities for #cancer antigen discovery, mRNA design, and manufacturing ... https://www.rna-seqblog.com/md-anderson-and-curevac-enter-strategic-collaboration-to-develop-novel-cancer-vaccines/?utm_source=dlvr.it&utm_medium=tumblr