Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is responsible for coronavirus disease of 2019 (COVID‐19) that infected more than 760 million people worldwide with over 6.8 million deaths to date. COVID‐19 is one of the most challenging diseases of our times due to the nature of its spread, its effect on multiple organs, and an inability to predict disease prognosis, ranging from being completely asymptomatic to death. Upon infection, SARS‐CoV‐2 alters the host immune response by changing host‐transcriptional machinery. MicroRNAs (miRNAs) are regarded as post‐transcriptional regulators of gene expression that can be perturbed by invading viruses. Several in vitro and in vivo studies have reported such dysregulation of host miRNA expression upon SARS‐CoV‐2 infection. Some of this could occur as an anti‐viral response of the host to the viral infection. Viruses themselves can counteract that response by mounting their own pro‐viral response that facilitates virus infection, an aspect which may cause pathogenesis. Thus, miRNAs could serve as possible disease biomarkers in infected people. In the current review, we have summarised and analysed the existing data about miRNA dysregulation in patients infected with SARS‐CoV‐2 to determine their concordance between studies, and identified those that could serve as potential biomarkers during infection, disease progression, and death, even in people with other co‐morbidities. Having such biomarkers can be vital in not only predicting COVID‐19 prognosis, but also the development of novel miRNA‐based anti‐virals and therapeutics which can become invaluable in case of the emergence of new viral variants with pandemic potential in the future.

Background: This study investigated the anticancer potential of the medicinal herb,Cleome droserifolia(CD),a local plant of the Arabian Peninsula.C. droserifoliais traditionally known for its rubefacient, anti-diabetic, anti-oxidant, and anti-inflammatory properties.Methods: Organic fractions of the aerial parts ofCleome droserifoliaharvested from the Arabian Peninsula were tested in human breast and cervical cancer cell lines for their anticancer potential. This was accomplished by using biochemical and cellular assays, including MTT, caspase Glo, western blot, and annexin V/propidium iodide-based flow cytometry analyses.Results: Test of the dichloromethane fraction of the methanolic extract ofC. droserifolia,(CDD) revealed potent cytotoxic activity (from 70 to 90%) against several human cancer cell lines, including MCF-7, MDA-MB-231, and HeLa. Further characterization of the CDD fraction in MCF-7 cells revealed that it could activate the enzymatic activity of various caspases in a statistically significant manner, and induce cleavage of both caspase 7 and poly ADB ribose polymerase (PARP) proteins, but not the ethyl acetate fraction. Test of the ability of CDD to induce early signs of apoptosis was validated by annexin V/propidium iodide assay using FACS analysis. Induction of apoptosis was completely reversed by the classic pan inhibitor of apoptosis, Z-VAD-FMK, reducing early apoptosis from 29.7 to 0.6%, confirming that CDD could induce caspase-dependent apoptosis.Conclusions: Altogether, our results reveal thatC. droserifoliais a valuable medicinal plant with bioactive molecules that can induce apoptosis in human cancer cells. Thus, this plant should be explored further for its potential as an anticancer natural therapy as well as the isolation of novel molecules with anticancer properties.

This study systematically analyzed the anticancer potential of Acridocarpus orientalis (AO), a traditional medicinal plant of the Arabian Peninsula/East Africa known for its anti-inflammatory and pain relief properties. Tests of serial organic fractions from methanolic extracts of its leaves and stems revealed that only some fractions showed anti-proliferative potential with the dichloromethane fraction from leaves (AOD (L)) showing the most cytotoxic effect against both breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cell lines. The n-butanol fraction from the stems (AOB (S)), on the other hand, was more effective against cervical cancer cells and did not harm the normal cells. Further characterization of the mode of cell killing revealed that AOD (L) depended more on non-apoptotic pathways for its cytotoxicity in breast cancer cells, while it could activate some apoptosis and necroptosis in HeLa cells. The AOB (S) fraction could primarily activate apoptosis and some necroptosis in HeLa cells. Both fractions perturbed autophagy, but in a dissimilar manner. Thus, different parts of A. orientalis revealed variable potential to induce cell death in cancer cells via apoptotic and non-apoptotic pathways, making A. orientalis a valuable plant for the exploration of anticancer bioactive reagents, some of which may be protective for normal cells.

This study aimed to identify miRNA-based biomarkers in a multi-ethnic cohort of SARS-CoV-2-infected individuals to enhance preparedness for future variants of concern. A total of 31 healthy controls and 154 infected patients were enrolled, from which 13 matched controls and 38 infected nasal swab samples were analyzed using miRNA sequencing, followed by qRT-PCR validation. Among the 1788 miRNAs detected, 14 differentially expressed miRNAs and four novel miRNAs were identified, with novel-miR-264-5p showing a ≥ 2-fold change. Correlation with clinical markers highlighted several miRNAs as potential prognostic biomarkers. Seven miRNAs, including miR-146b-3p, miR-154-5p, miR-5010-3p, miR-127-3p, miR-335-3p, miR-30c-5p, and miR-202-5p, showed strong prognostic potential. Combined ROC analysis demonstrated that a panel of top-performing miRNAs significantly enhanced diagnostic accuracy (AUC 0.939–0.972; p < 0.0001). Moreover, integrating miRNA biomarkers with clinical parameters further improved performance (AUC = 0.982; p < 0.0001). miR-146b-3p, detected exclusively in infected patients, emerged as a highly specific biomarker. Several nasal miRNAs mirrored blood profiles, highlighting the utility of nasal swabs for non-invasive monitoring. Collectively, these findings suggest that miRNA-based biomarkers, alone or combined with clinical markers, offer a promising platform for COVID-19 prognosis and diagnosis, and lay groundwork for future miRNA-based antiviral strategies.

Mouse mammary tumor virus (MMTV) is a betaretrovirus that causes breast cancer in mice. The mouse mammary epithelial cells are the most permissive cells for MMTV, expressing the highest levels of virus upon infection and being the ones later transformed by the virus due to repeated rounds of infection/superinfection and integration, leading eventually to mammary tumors. The aim of this study was to identify genes and molecular pathways dysregulated by MMTV expression in mammary epithelial cells. Towards this end, mRNAseq was performed on normal mouse mammary epithelial cells stably expressing MMTV, and expression of host genes was analyzed compared with cells in its absence. The identified differentially expressed genes (DEGs) were grouped on the basis of gene ontology and relevant molecular pathways. Bioinformatics analysis identified 12 hub genes, of which 4 were up-regulated (Angp2, Ccl2, Icam, and Myc) and 8 were down-regulated (Acta2, Cd34, Col1a1, Col1a2, Cxcl12, Eln, Igf1, and Itgam) upon MMTV expression. Further screening of these DEGs showed their involvement in many diseases, especially in breast cancer progression when compared with available data. Gene Set Enrichment Analysis (GSEA) identified 31 molecular pathways dysregulated upon MMTV expression, amongst which the PI3-AKT-mTOR was observed to be the central pathway down-regulated by MMTV. Many of the DEGs and 6 of the 12 hub genes identified in this study showed expression profile similar to that observed in the PyMT mouse model of breast cancer, especially during tumor progression. Interestingly, a global down-regulation of gene expression was observed, where nearly 74% of the DEGs in HC11 cells were repressed by MMTV expression, an observation similar to what was observed in the PyMT mouse model during tumor progression, from hyperplasia to adenoma to early and late carcinomas. Comparison of our results with the Wnt1 mouse model revealed further insights into how MMTV expression could lead to activation of the Wnt1 pathway independent of insertional mutagenesis. Thus, the key pathways, DEGs, and hub genes identified in this study can provide important clues to elucidate the molecular mechanisms involved in MMTV replication, escape from cellular anti-viral response, and potential to cause cell transformation. These data also validate the use of the MMTV-infected HC11 cells as an important model to study early transcriptional changes that could lead to mammary cell transformation.

The mouse mammary tumor virus (MMTV) is a well-known cause of breast cancer in mice. Previously, we have shown that MMTV dysregulates expression of the host miR-17-92 cluster in MMTV-infected mammary glands and MMTV-induced tumors. This cluster, better known as oncomiR-1, is frequently dysregulated in cancers, particularly breast cancer. In this study, our aim was to uncover a functional interaction between MMTV and the cluster. Our results reveal that MMTV expression led to dysregulation of the cluster in both mammary epithelial HC11 and HEK293T cells with the expression of miR-92a cluster member being affected the most. Conversely, overexpression of the whole or partial cluster significantly repressed MMTV expression. Notably, overexpression of cluster member miR-92a alone repressed MMTV expression to the same extent as overexpression of the complete/partial cluster. Inhibition of miR-92a led to nearly a complete restoration of MMTV expression, while deletion/substitution of the miR-92a seed sequence rescued MMTV expression. Dual luciferase assays identified MMTV genomic RNA as the potential target of miR-92a. These results show that the miR-17-92 cluster acts as part of the cell’s well-known miRNA-based anti-viral response to thwart incoming MMTV infection. Thus, this study provides the first evidence highlighting the biological significance of host miRNAs in regulating MMTV replication and potentially influencing tumorigenesis.