Chromosomal translocations are products of the illegitimate repair of DNA double-strand breaks (DSBs). Their formation can bring about significant structural and molecular changes in the cell that can be physiologically and pathologically relevant. The induced changes may lead to serious and life-threatening diseases such as cancer. As a growing body of evidence suggests, the formation of chromosomal translocation is not only affected by the mere close spatial proximity of gene loci as potential translocation partners. Several factors may affect formation of chromosomal translocations, including chromatin motion to the potential sources of DSBs in the cell. While these can be apparently random events, certain chromosomal translocations appear to be cell-type-specific. In this review, we discuss how chromosomal translocations are formed and explore how different cellular factors contribute to their formation.

Alzheimer’s disease (AD) is the leading cause of dementia globally, having a pathophysiology that is complex and multifactorial. Recent findings highlight the significant role of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs) in the molecular mechanisms underlying AD. These ncRNAs are involved in critical biological processes such as cell proliferation, apoptosis, oxidative stress, amyloid-beta aggregation, tau phosphorylation, neuroinflammation, and autophagy, which are pivotal in AD development and progression. This systematic review aims to consolidate current scientific knowledge on the role of ncRNAs in AD, making it the first to encompass the four types of ncRNAs associated with the disease. Our comprehensive search and analysis reveal that ncRNAs not only play crucial roles in the pathogenesis of AD but also hold potential as biomarkers for its early detection and as novel therapeutic targets. Specifically, the findings underscore the significance of miRNAs in regulating genes involved in key AD pathways such as activin receptor signaling pathway, actomyosin contractile ring organization, and advanced glycation endproducts-receptor advanced glycation endproducts (AGE-RAGE) signaling pathway. This review also highlights the potential of ncRNAs in unveiling novel diagnostic and therapeutic strategies, emphasizing the need for further research to validate their clinical utility. Our systematic exploration provides a foundation for future bioinformatic analyses and the development of ncRNA-based precision medicine approaches for AD, offering new insights into the disease’s molecular pathology and paving the way for innovative treatment strategies.Systematic review registration: PROSPERO, https://www.crd.york.ac.uk/prospero/, CRD42022355307.

Hepatocellular carcinoma (HCC) is a type of liver cancer with a poor prognosis for survival given the complications it bears on the patient. Though damages to the liver are acknowledged prodromic factors, the precise molecular aetiology remains ill-defined. However, many genes coding for proteins involved in calcium (Ca²⁺) homeostasis emerge as either mutated or deregulated. Ca²⁺ is a versatile signalling messenger that regulates functions that prime and drive oncogenesis, favouring metabolic reprogramming and gene expression. Ca²⁺ is present in cell compartments, between which it is trafficked through a network of transporters and exchangers, known as the Ca²⁺ transportome. The latter regulates and controls Ca²⁺ dynamics and tonicity. In HCC, the deregulation of the Ca²⁺ transportome contributes to tumorigenesis, the formation of metastasizing cells, and evasion of cell death. In this review, we reflect on these aspects by summarizing the current knowledge of the Ca²⁺ transportome and overviewing its composition in the plasma membrane, endoplasmic reticulum, and the mitochondria.

Introduction: COVID-19 diagnosis was one of the most pressing needs during the early stages of the pandemic. Its entire procedure has inherent biosafety risks that if not properly managed and mitigated can be life threatening. Cognizant of this vital aspect, the Department of Health (DOH) imposed a biosafety training requirement to all laboratories and institutions before they could perform COVID-19 diagnostic testing. But with the mandatory lockdown, conventional face-to-face training could not be conducted. To address this need, the Biosafety Education and Awareness Training COVID-19 Online Program was offered by the National Training Center for Biosafety and Biosecurity of the University of the Philippines Manila. Methods and Materials: This online training program implemented a distance learning approach made available through the Canvas Learning Management System. It consisted of seven modules on biosafety that were sufficient enough to capacitate the participants with information for them to effectively implement a biorisk management system. The participants were evaluated based on quiz, examination, and case analysis. Certificates of completion were awarded to participants who passed all evaluation methods. Results: A total of 3371 trainees from various medical professions passed and obtained the certificate. This resulted in >100 DOH-accredited COVID-19 testing laboratories by the end of 2020. Discussion and Conclusion: The online availability of this program proved to be an effective innovative solution to a unique problem. Therefore, this training program demonstrated that biosafety training can be effectively conducted online and in a distance learning approach.

Facteurs affectant les translocations chromosomiques dans les cellules: La plupart des translocations chromosomiques liées au cancer semblent être spécifiques d’un type cellulaire donné. Par exemple, la translocation MYC-IGH a toujours été rapportée et décrite dans les cellules B, et non dans d'autres types de cellules. Cela peut être dû soit aux translocations spontanées entre différents loci et qui sont spécifiques du type cellulaire, soit à la sélection post-translocation de cellules qui ont acquis un avantage sélectif de survie, tel qu'une croissance accrue ou une résistance à l'apoptose. Cette observation a été étudiée expérimentalement par induction simultanée de plusieurs cassures double brin (CDB) à des loci spécifiques pour générer des translocations chromosomiques spécifiques dans différents modèles cellulaires : RPMI8866 (lymphoïde, cellule B), Jurkat (lymphoïde, cellule T), K562 (myéloïde), MRC5 (fibroblaste pulmonaire) et Hek-293 (embryonnaire rénal, épithélial). À cet effet, un protocole d'électrotransfection a été optimisé pour transfecter ces cellules avec des plasmides codant pour la nucléase Cas9 et des ARN guides, y compris celles difficiles à transfecter telles que les cellules B. Quatre gènes ont été ciblés pour former deux combinaisons de 3-CDB chacune: MYC-IGH-AML (MIA) et AML-ETO-IGH (AEI). Dans chaque type cellulaire, l’une ou l’autre des combinaisons de 3-CDB a été induite en utilisant le protocole d'électrotransfection optimisé. Les translocations générées ont ensuite été mesurées par qPCR à l'aide d'amorces de PCR spécifiques à la translocation. Les résultats ont montré la fréquence des différentes translocations spécifiques pour chaque type de cellule après induction de CDB simultanées. Pour la combinaison MIA, la translocation oncogène MYC-IGH avait la fréquence la plus élevée après induction des CDB. Pour la combinaison AEI, la translocation ETO-IGH jamais décrite auparavant, et non la translocation oncogène AML-ETO, avait la fréquence la plus élevée après induction simultanée de CDB. Il a en outre été montré que des translocations chromosomiques étaient générées indépendamment de la position radiale nucléaire, de l'activité de transcription et de l'accessibilité de la chromatine des loci. Seule la proximité spatiale entre les loci après l'induction de la CDB était corrélée à la fréquence observée des translocations, soutenant le modèle du «breakage first» dans les mécanismes de formation des translocations. De plus, la culture à long terme jusqu’à 60 jours des cellules avec les translocations chromosomiques générées a montré une survie variable des différents types cellulaires. Ce qui suppose que l’avantage sélectif de survie acquis après la translocation est spécifique du type cellulaire. Dans l'ensemble, les résultats démontrent que les translocations chromosomiques peuvent être générées après induction expérimentale de CDB dans n'importe quel type de cellule, mais la persistance des cellules avec translocation dépend de l'avantage de survie sélectif que la translocation chromosomique confère à la cellule et qui est spécifique d’un type cellulaire.