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Background: Neuroblastoma (NB) is one of the most devastating malignancies in children, accounting for a high mortality rate due to limited treatment options. This study is aimed at elucidating the role of the ferroptosis‐related EIF2S1 gene in NB pathogenesis and exploring its potential as a therapeutic target. Methods: We conducted comprehensive bioinformatics analyses utilizing the FerrDb database and NB‐related transcriptomics data to investigate the role of EIF2S1 in NB. Changes in EIF2S1 expression were subsequently validated in NB tissues and cell lines. Loss‐of‐function experiments were performed in SK‐N‐SH and IMR‐32 cell lines through shRNA‐mediated EIF2S1 knockdown. The impact of EIF2S1 knockdown on the tumorigenesis of SK‐N‐SH cells was assessed in nude mice. Results: Bioinformatics analyses revealed a significant association between elevated EIF2S1 expression and poor prognosis in NB patients. The increased levels of EIF2S1 expression were confirmed in NB tissues and cancerous cell lines. Furthermore, EIF2S1 overexpression was linked to translational regulation and immune cell infiltration modulation. Silencing of EIF2S1 resulted in the suppression of cell proliferation, migration, and tumorigenicity in NB cells. Additionally, EIF2S1 knockdown led to an accumulation of iron and oxidative stress, as well as a reduction in GPX4 and SLC7A11 expression. Conclusion: Our findings indicate that EIF2S1 appears to facilitate the progression of NB by protecting tumor cells from ferroptosis through modulating GPX4 and SLC7A11 expression. Consequently, EIF2S1 may serve as a potential therapeutic target for the management of NB. [ABSTRACT FROM AUTHOR]

Telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) constitute the core telomerase enzyme that maintains the length of telomeres. Telomere maintenance is affected in a broad range of cancer and degenerative disorders. Taking advantage of gain‐ and loss‐of‐function approaches, we show that Argonaute 2 (AGO2) promotes telomerase activity and stimulates the association between TERT and TERC. AGO2 depletion results in shorter telomeres as well as in lower proliferation rates in vitro and in vivo. We also demonstrate that AGO2 interacts with TERC and with a newly identified sRNA (terc‐sRNA), arising from the H/ACA box of TERC. Notably, terc‐sRNA is sufficient to enhance telomerase activity when overexpressed. Analyses of sRNA‐Seq datasets show that terc‐sRNA is detected in primary human tissues and increases in tumors as compared to control tissues. Collectively, these data uncover a new layer of complexity in the regulation of telomerase activity by AGO2 and might lay the foundation for new therapeutic targets in tumors and telomere diseases. Synopsis: AGO2 promotes telomerase activity and the interaction between TERT and TERC. AGO2 further binds TERC and a small RNA derived from TERC, terc‐sRNA, that also stimulates telomerase activity. AGO2 depletion results in telomere shortening, impairment of association between TERT and TERC RNA and decrease of telomerase activity.AGO2 interacts with TERC RNA via CR4/CR5 and TBE domains and binds a small RNA (terc‐sRNA), which arises from the 3′end of TERC.Overexpression of terc‐sRNA stimulates telomerase activity. AGO2 promotes telomerase activity and the interaction between TERT and TERC. AGO2 further binds TERC and a small RNA derived from TERC, terc‐sRNA, that also stimulates telomerase activity. [ABSTRACT FROM AUTHOR]

We report on a hitherto poorly characterized class of genes that are expressed in all tissues, except in one. Often, these genes have been classified as housekeeping genes, based on their nearly ubiquitous expression. However, the specific repression in one tissue defines a special class of "disallowed genes." In this paper, we used the intersection-union test to screen for such genes in a multi-tissue panel of genome-wide mRNA expression data. We propose that disallowed genes need to be repressed in the specific target tissue to ensure correct tissue function. We provide mechanistic data of repression with two metabolic examples, exercise-induced inappropriate insulin release and interference with ketogenesis in liver. Developmentally, this repression is established during tissue maturation in the early postnatal period involving epigenetic changes in histone methylation. In addition, tissue-specific expression of microRNAs can further diminish these repressed mRNAs. Together, we provide a systematic analysis of tissue-specific repression of housekeeping genes, a phenomenon that has not been studied so far on a genome-wide basis and, when perturbed, can lead to human disease. [ABSTRACT FROM AUTHOR]

Objective and Rationale: Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, manifests with chronic intestinal inflammation and frequent sequential fibrosis. Current pharmacological therapies may show harmful side effects and are not useful for prevention or resolution of fibrosis. Thus, the use of alternative therapies is emerging as a novel useful approach. Previous results suggest that Scutellaria baicalensis Georgi (SBG) and Boswellia serrata (BS) display anti-inflammatory properties. The aim of this study was to investigate in intestinal epithelial cells and fibroblasts the anti-inflammatory and anti-fibrotic potential of SBG and BS, alone or in combination., Methods: Human colorectal adenocarcinoma cells (HT29), human intestinal epithelial cells (HIEC6) and human colon fibroblasts (CCD-18Co) were used. Cells were pretreated with SBG and BS and then exposed to pro-inflammatory and pro-fibrotic cytokines., Results: SBG and BS extracts significantly decreased pro-inflammatory cytokine expression and improved epithelial restitution in HT29 and HIEC6 cells. Besides, fibrotic marker expression, including SNAIL, ACTA2, ZNF281, was strongly reduced. Colon myofibroblasts treated with SBG and BS showed a significant decrease of fibrotic markers as well., Conclusions: SBG and BS extracts significantly reduce inflammation and impair fibrosis in intestinal epithelial cells and colon myofibroblasts. No cooperative effect is observed., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak demonstrates the potential of coronaviruses, especially bat-derived beta coronaviruses to rapidly escalate to a global pandemic that has caused deaths in the order of several millions already. The huge efforts put in place by the scientific community to address this emergency have disclosed how the implementation of new technologies is crucial in the prepandemic period to timely face future ecological crises. In this context, we argue that metagenomics and new approaches to understanding ecosystems and biodiversity offer veritable prospects to innovate therapeutics and diagnostics against novel and existing infectious agents. We discuss the opportunities and challenges associated with the science of metagenomics, specifically with an eye to inform and prevent future ecological crises and pandemics that are looming on the horizon in the 21st century.

Metagenomics is not only one of the newest omics system science technologies but also one that has arguably the broadest set of applications and impacts globally. Metagenomics has found vast utility not only in environmental sciences, ecology, and public health but also in clinical medicine and looking into the future, in planetary health. In line with the One Health concept, metagenomics solicits collaboration between molecular biologists, geneticists, microbiologists, clinicians, computational biologists, plant biologists, veterinarians, and other health care professionals. Almost every ecological niche of our planet hosts an extremely diverse community of organisms that are still poorly characterized. Detailed characterization of the features of such communities is instrumental to our comprehension of ecological, biological, and clinical complexity. This expert review article evaluates how metagenomics is improving our knowledge of microbiota composition from environmental to human samples. Furthermore, we offer an analysis of the common technical and methodological challenges and potential pitfalls arising from metagenomics approaches, such as metagenomics study design, data processing, and interpretation. All in all, at this critical juncture of further growth of the metagenomics field, it is time to critically reflect on the lessons learned and the future prospects of next-generation metagenomics science, technology, and conceivable applications, particularly from the standpoint of a metagenomics methodology perspective.

The analysis of microbiota composition in humans, animals, and built environments is important because of emerging roles and applications in a broad range of disease and ecological phenotypes. Next Generation Sequencing is the current method of choice to characterize microbial community composition. The taxonomic profile of a microbial community can be obtained either by shotgun analysis of random DNA fragments or through 16S ribosomal RNA gene (rDNA) amplicon sequencing. It has been previously shown that the 16S rDNA amplicon sequencing approach yields quantitatively and qualitatively different results compared to shotgun metagenomics when the two techniques are used to assess microbial community composition on the same samples. However, most of such comparisons were either based on the recovery of 16S rDNA sequences in the shotgun metagenomics data or limited to a single microbiome or synthetic samples. Direct comparison of shotgun metagenomics and 16S rDNA amplicon sequencing on the same samples was performed only once in the recent literature, suggesting that the two methods yield comparable results. Here, we set out to compare the outcome of these two alternative approaches to the microbiome characterization in human gut microbiomes from stool samples. To this end, we processed six different samples with both techniques. We report here that shotgun next generation sequencing metagenomics allows much deeper characterization of the microbiome complexity, allowing identification of a larger number of species for each sample, compared to 16S rDNA amplicon sequencing. Further comparative studies in independent samples are called for.