Adaptive resistance to Biocides and implications of cross-resistance to Antimicrobial Agents in Foodborne Pathogens.

This study was focused on the potential for adaptive resistance in Salmonella and Escherichia coli to commonly used biocides, to identify resistance strategies and any cross-resistance to antibiotics. Bacteria were serially exposed in sub-inhibitory concentrations of biocides and adaptive resistance was observed in all strains investigated. Erythromycin-resistant Salm. Enteritidis did not cross-resist to biocides, whereas erythromycin-resistant Salm. Typhimurium express cross-resistance to chlorohexidine. Benzalkonium chloride-resistant Salm. Virchow showed an elevated resistance to chlorohexidine, however chlorohexidine-resistant Salm. Virchow did not demonstrate it back

Mechanisms of resistance in Salmonella enterica

The aim of this study was to promote resistance in Salmonella enterica serovar Enteritidis, Typhimurium, and Virchow to commonly used antibacterials and to identify mechanisms underlying any resistance obtained. Strains were exposed to various biocides and following each passage adaptive resistance was recorded. Permeability changes in the outer membrane, including LPS, cell surface charge and hydrophobicity and efflux were investigated as possible resistance mechanism candidates. The outer membrane and LPS bands were analysed by SDS-PAGE and visualised by Coomassie blue and silver staining. The cell surface charge and hydrophobicity were investigated employing microelectrophoresis and microbial adhesion to hydrocarbons assay, respectively. Efflux activity was examined by comparing resistance in pre- and post-adapted strains in the presence of reserpine. The outer membrane and LPS did not reveal any significant changes. Most of the parent strains were not significantly hydrophobic, whereas adapted were. An active efflux system was associated with benzalkonium chloride and chlorohexidine resistance

MicroRNA expression profiles in pediatric dysembryoplastic neuroepithelial tumors.

© Springer Science+Business Media New York 2015Among noncoding RNAs, microRNAs (miRNAs) have been most extensively studied, and their biology has repeatedly been proven critical for central nervous system pathological conditions. The diagnostic value of several miRNAs was appraised in pediatric dysembryoplastic neuroepithelial tumors (DNETs) using miRNA microarrays and receiving operating characteristic curves analyses. Overall, five pediatric DNETs were studied. As controls, 17 samples were used: the FirstChoice Human Brain Reference RNA and 16 samples from deceased children who underwent autopsy and were not present with any brain malignancy. The miRNA extraction was carried out using the mirVANA miRNA Isolation Kit, while the experimental approach included miRNA microarrays covering 1211 miRNAs. Quantitative real-time polymerase chain reaction was performed to validate the expression profiles of miR-1909* and miR-3138 in all samples initially screened with miRNA microarrays. Our findings indicated that miR-3138 might act as a tumor suppressor gene when down-regulated and miR-1909* as a putative oncogenic molecule when up-regulated in pediatric DNETs compared to the control cohort. Subsequently, both miRNA signatures might serve as putative diagnostic biomarkers for pediatric DNETs.Peer reviewedFinal Accepted Versio

SV2B /miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme

© 2024 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Glioblastoma (GBM) is a heterogenous primary brain tumour that is characterised with unfavourable patient prognosis. The identification of biomarkers for managing brain malignancies is of utmost importance. MicroRNAs (miRNAs) are small, non-coding RNAs implicated in cancer development. This study aimed to assess the prognostic significance of miRNAs and their gene targets in GBM. An in silico approach was employed to investigate the differentially expressed miRNAs in GBM. The most dysregulated miRNAs were identified and analysed via Sfold in association with their gene target. The candidate gene was studied via multi-omics approaches, followed by in vitro and in vivo experiments. The in silico analyses revealed that miR-128a and miR-34a were significantly downregulated within GBM. Both miRNAs displayed high binding affinity to the synaptic vesicle glycoprotein 2B (SV2B) 3′ untranslated region (3′UTR). SV2B exhibited upregulation within brain regions with high synaptic activity. Significantly higher SV2B levels were observed in high grade brain malignancies in comparison to their normal counterparts. SV2B expression was observed across the cytoplasm of GBM cells. Our findings underscored the downregulated expression patterns of miR-128a and miR-34a, alongside the upregulation of SV2B in GBM suggesting the importance of the SV2B/miR-34a/miR-128 axis as a potential prognostic approach in GBM management.Peer reviewe

Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology

© 2024 The Author(s). Published by Cambridge University Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/The host immune system status remains an unresolved mystery among several malignancies. An immune-compromised state or smart immune-surveillance tactics orchestrated by cancer cells are the primary cause of cancer invasion and metastasis. Taking a closer look at the tumour-immune microenvironment, a complex network and crosstalk between infiltrating immune cells and cancer cells mediated by cytokines, chemokines, exosomal mediators and shed ligands are present. Cytokines such as interleukins can influence all components of the tumour microenvironment (TME), consequently promoting or suppressing tumour invasion based on their secreting source. Interleukin-10 (IL-10) is an interlocked cytokine that has been associated with several types of malignancies and proved to have paradoxical effects. IL-10 has multiple functions on cellular and non-cellular components within the TME. In this review, the authors shed the light on the regulatory role of IL-10 in the TME of several malignant contexts. Moreover, detailed epigenomic and pharmacogenomic approaches for the regulation of IL-10 were presented and discussed.Peer reviewe

Editorial: Recent breakthroughs in the decoding of circulating nucleic acids and their applications to human diseases

© 2023 El-Daly, Talaat, Braoudaki, Youness and Cho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).Peer reviewe

SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme

Data availability: The datasets generated and/or analysed during the current study are available upon reasonable request. Researchers interested in accessing the data can contact the corresponding authors.Supplementary Information is available online at: https://www.nature.com/articles/s41598-024-55917-6#Sec16 .Glioblastoma (GBM) is a heterogenous primary brain tumour that is characterised with unfavourable patient prognosis. The identification of biomarkers for managing brain malignancies is of utmost importance. MicroRNAs (miRNAs) are small, non-coding RNAs implicated in cancer development. This study aimed to assess the prognostic significance of miRNAs and their gene targets in GBM. An in silico approach was employed to investigate the differentially expressed miRNAs in GBM. The most dysregulated miRNAs were identified and analysed via Sfold in association with their gene target. The candidate gene was studied via multi-omics approaches, followed by in vitro and in vivo experiments. The in silico analyses revealed that miR-128a and miR-34a were significantly downregulated within GBM. Both miRNAs displayed high binding affinity to the synaptic vesicle glycoprotein 2B (SV2B) 3′ untranslated region (3′UTR). SV2B exhibited upregulation within brain regions with high synaptic activity. Significantly higher SV2B levels were observed in high grade brain malignancies in comparison to their normal counterparts. SV2B expression was observed across the cytoplasm of GBM cells. Our findings underscored the downregulated expression patterns of miR-128a and miR-34a, alongside the upregulation of SV2B in GBM suggesting the importance of the SV2B/miR-34a/miR-128 axis as a potential prognostic approach in GBM management

The frequency of NPM1 mutations in childhood acute myeloid leukemia

<p>Abstract</p> <p>Background</p> <p>Mutations in the nucleophosmin <it>(NPM1) </it>gene have been solely associated with childhood acute myeloid leukemia (AML). We evaluated the frequency of <it>NPM1 </it>mutations in childhood AML, their relation to clinical and cytogenetic features and the presence of common <it>FLT3 </it>and <it>RAS </it>mutations.</p> <p>Results</p> <p><it>NPM1 </it>mutations were found in 8% of cases. They involved the typical type 'A' mutation and one novel mutation characterized by two individual base pair substitutions, which resulted in 2 amino acid changes (W290) and (S293) in the NPM protein. <it>FLT3</it>/ITD mutations were observed in 12% of the cases and in one <it>NPM1-</it>mutated case bearing also t(8;21) (q22;q22). No common <it>RAS </it>mutations were identified.</p> <p>Conclusions</p> <p>A relatively consistent <it>NPM1 </it>mutation rate was observed, but with variations in types of mutations. The role of different types of <it>NPM1 </it>mutations, either individually or in the presence of other common gene mutations may be essential for childhood AML prognosis.</p

A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma

© 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the Creative Commons Attribution-Non Commercial-No Derivatives CC BY-NC-ND licence, https://creativecommons.org/licenses/by-nc-nd/4.0/Tumor microenvironment is an intricate web of stromal and immune cells creating an immune suppressive cordon around the tumor. In hepatocellular carcinoma (HCC), Tumor microenvironment is a formidable barrier towards novel immune therapeutic approaches recently evading the oncology field. In this study, the main aim was to identify the intricate immune evasion tactics mediated by HCC cells and to study the epigenetic modulation of the immune checkpoints; Programmed death-1 (PD-1)/ Programmed death-Ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT)/Cluster of Differentiation 155 (CD155) at the tumor-immune synapse. Thus, liver tissues, PBMCs and sera were collected from Hepatitis C Virus (HCV), HCC as well as healthy individuals. Screening was performed to PD-L1/PD-1 and CD155/TIGIT axes in HCC patients. PDL1, CD155, PD-1 and TIGIT were found to be significantly upregulated in liver tissues and peripheral blood mononuclear cells (PBMCs) of HCC patients. An array of long non-coding RNAs (lncRNAs) and microRNAs validated to regulate such immune checkpoints were screened. The lncRNAs; CCAT-1, H19, and MALAT-1 were all significantly upregulated in the sera, PBMCs, and tissues of HCC patients as compared to HCV patients and healthy controls. However, miR-944–5p, miR-105–5p, miR-486–5p, miR-506–5p, and miR-30a-5p were downregulated in the sera and liver tissues of HCC patients. On the tumor cell side, knocking down of lncRNAs—CCAT-1, MALAT-1, or H19—markedly repressed the co-expression of PD-L1 and CD155 and accordingly induced the cytotoxicity of co-cultured primary immune cells. On the immune side, ectopic expression of the under-expressed microRNAs; miR-486–5p, miR-506–5p, and miR-30a-5p significantly decreased the transcript levels of PD-1 in PBMCs with no effect on TIGIT. On the other hand, ectopic expression of miR-944–5p and miR-105–5p in PBMCs dramatically reduced the co-expression of PD-1 and TIGIT. Finally, all studied miRNAs enhanced the cytotoxic effects of PBMCs against Huh7 cells. However, miR-105–5p showed the highest augmentation for PBMCs cytotoxicity against HCC cells. In conclusion, this study highlights a novel co-targeting strategy using miR-105–5p mimics, MALAT-1, CCAT-1 and H19 siRNAs to efficiently hampers the immune checkpoints; PD-L1/PD-1 and CD155/TIGIT immune evasion properties in HCC.Peer reviewe

In Silico and In Vitro Mapping of Receptor-Type Protein Tyrosine Phosphatase Receptor Type D in Health and Disease: Implications for Asprosin Signalling in Endometrial Cancer and Neuroblastoma

Data Availability Statement: Data will be available upon reasonable request.Background: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) is involved in the regulation of cell growth, differentiation, and oncogenic transformation, as well as in brain development. PTPRD also mediates the effects of asprosin, which is a glucogenic hormone/adipokine derived following the cleavage of the C-terminal of fibrillin 1. Since the asprosin circulating levels are elevated in certain cancers, research is now focused on the potential role of this adipokine and its receptors in cancer. As such, in this study, we investigated the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). Methods: An array of in silico tools, in vitro models, tissue microarrays (TMAs), and liquid biopsies were employed to determine the gene and protein expression of PTPRD in healthy tissues/organs and in patients with EC and GBM. Results: PTPRD exhibits high expression in the occipital lobe, parietal lobe, globus pallidus, ventral thalamus, and white matter, whereas in the human placenta, it is primarily localised around the tertiary villi. PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated with obesity, whilst it is also expressed in the peripheral leukocytes. The EC TMAs revealed abundant PTPRD expression in both low- and high-grade tumours. Asprosin treatment upregulated the expression of PTPRD only in syncytialised placental cells. Conclusions: Our data indicate that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Future studies are needed to explore the potential molecular mechanisms/signalling pathways that link PTPRD and asprosin in cancer.This research was funded by GRACE, Registered Charity No. 1189729 and by the General Charities of the City of Coventry, Registered Charity No. 216235