DNA Damage Repair in Brain Tumor Immunotherapy

With the gradual understanding of tumor development, many tumor therapies have been invented and applied in clinical work, and immunotherapy has been widely concerned as an emerging hot topic in the last decade. It is worth noting that immunotherapy is nowadays applied under too harsh conditions, and many tumors are defined as “cold tumors” that are not sensitive to immunotherapy, and brain tumors are typical of them. However, there is much evidence that suggests a link between DNA damage repair mechanisms and immunotherapy. This may be a breakthrough for the application of immunotherapy in brain tumors. Therefore, in this review, first, we will describe the common pathways of DNA damage repair. Second, we will focus on immunotherapy and analyze the mechanisms of DNA damage repair involved in the immune process. Third, we will review biomarkers that have been or may be used to evaluate immunotherapy for brain tumors, such as TAMs, RPA, and other molecules that may provide a precursor assessment for the rational implementation of immunotherapy for brain tumors. Finally, we will discuss the rational combination of immunotherapy with other therapeutic approaches that have an impact on the DNA damage repair process in order to open new pathways for the application of immunotherapy in brain tumors, to maximize the effect of immunotherapy on DNA damage repair mechanisms, and to provide ideas and guidance for immunotherapy in brain tumors.

Developmental origins of cell heterogeneity in the human lung

The lung contains numerous specialized cell-types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a first comprehensive topographic atlas of early human lung development. We report 83 cell states, several spatially-resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated scRNA-Seq and spatial transcriptomics into a web-based, open platform for interactive exploration. To illustrate the utility of our approach we show distinct states of secretory and neuroendocrine cells, largely overlapping with the programs activated either during lung fibrosis or small cell lung cancer progression. We define the origin of uncharacterized airway fibroblasts associated with airway smooth muscle in bronchovascular bundles, and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.

Self-Healing Materials for Electronics Applications

Self-healing materials have been attracting the attention of the scientists over the past few decades because of their effectiveness in detecting damage and their autonomic healing response. Self-healing materials are an evolving and intriguing field of study that could lead to a substantial increase in the lifespan of materials, improve the reliability of materials, increase product safety, and lower product replacement costs. Within the past few years, various autonomic and non-autonomic self-healing systems have been developed using various approaches for a variety of applications. The inclusion of appropriate functionalities into these materials by various chemistries has enhanced their repair mechanisms activated by crack formation. This review article summarizes various self-healing techniques that are currently being explored and the associated chemistries that are involved in the preparation of self-healing composite materials. This paper further surveys the electronic applications of self-healing materials in the fields of energy harvesting devices, energy storage devices, and sensors. We expect this article to provide the reader with a far deeper understanding of self-healing materials and their healing mechanisms in various electronics applications.

Commentary on: Xbp1s-Ddit3, DNA damage and pulmonary hypertension

In this commentary, we discuss new observations stating that spliced X-box-binding protein 1 (Xbp1s)-DNA damage-inducible transcript 3 (Ddit3) promotes monocrotaline (MCT)-induced pulmonary hypertension (Jiang et al., Clinical Science (2021) 135(21), https://doi.org/10.1042/CS20210612). Xbp1s-Ddit3 is involved in the regulation of endoplasmic reticulum stress but is also associated with DNA damage repair machinery. Pathologic DNA damage repair mechanisms have emerged as critical determinants of pulmonary hypertension development. We discuss the potential relationship among Xbp1s-Ddit3, DNA damage, and pulmonary hypertension. Although Xbp1s-Ddit3 contributes to the regulation of cell proliferation and apoptosis and the development of vascular lesions, whether Xbp1s is a friend or foe remains controversial.

Comparative assessment of electronic nicotine delivery systems aerosol and cigarette smoke on endothelial cell migration: the Replica Project

Cigarette smoking is associated with impairment of repair mechanisms necessary for vascular endothelium homeostasis. Reducing the exposure to smoke toxicants may result in the mitigation of the harmful effect on the endothelium and cardiovascular disease development. Previous investigations performed by the tobacco industries evaluated in vitro the effect of electronic cigarette (e-cig) compared to cigarette smoke demonstrating a significant reduction in endothelial cell migration inhibition following e-cig aerosol exposure. In the present study, we replicated one of these studies, evaluating the effects of cigarette smoke on endothelial cell migration compared to e-cig and heated tobacco products. We used a multi-center approach (ring-study) to verify the robustness and reliability of the results obtained in the replicated study. Consistently with the original study, we observed a substantial reduction of the effects of e-cig and tobacco heated products on endothelial cell migration compared to cigarette smoke. In conclusion, our study further confirms the importance of e-cig and tobacco heated products as a possible harm reduction strategy for cardiovascular diseases development in smokers.

Cryptomphalus aspersa Eggs Extract Potentiates Human Epidermal Stem Cell Regeneration and Amplification

Modern life and extended life expectancy have prompted the search for natural compounds alleviating skin aging. Evidence supports the beneficial effects on skin integrity and health from the topical administration of preparations of the mollusc Cryptomphalus aspersa eggs extract (IFC-CAF®) and suggests these effects are partly derived from an impact on skin renewal and repair mechanisms. The objective was to dissect in vitro the specific impact of IFC-CAF® on different parameters related to the regenerative potential, differentiation phenotype and exhaustion of skin stem cells. A prominent impact of IFC-CAF® was the induction of stratification and differentiated phenotypes from skin stem cells. IFC-CAF® slowed down the cell cycle at the keratinocyte DNA repair phase and, decelerated proliferation. However, it preserved the proliferative potential of the stem cells. IFC-CAF® reduced the DNA damage marker, γH2AX, and induced the expression of the transcription factor p53. These features correlated with significant protection in telomere shortening upon replicative exhaustion. Thus, IFC-CAF® helps maintain orderly cell cycling and differentiation, thus potentiating DNA repair and integrity. Our observations support the regenerative and repair capacity of IFC-CAF® on skin, through the improved mobilization and ordered differentiation of keratinocyte precursors and the enhancement of genome surveillance and repair mechanisms that counteract aging.

In Silico Investigation of the Biological Implications of Complex DNA Damage with Emphasis in Cancer Radiotherapy through a Systems Biology Approach

Different types of DNA lesions forming in close vicinity, create clusters of damaged sites termed as “clustered/complex DNA damage” and they are considered to be a major challenge for DNA repair mechanisms resulting in significant repair delays and induction of genomic instability. Upon detection of DNA damage, the corresponding DNA damage response and repair (DDR/R) mechanisms are activated. The inability of cells to process clustered DNA lesions efficiently has a great impact on the normal function and survival of cells. If complex lesions are left unrepaired or misrepaired, they can lead to mutations and if persistent, they may lead to apoptotic cell death. In this in silico study, and through rigorous data mining, we have identified human genes that are activated upon complex DNA damage induction like in the case of ionizing radiation (IR) and beyond the standard DNA repair pathways, and are also involved in cancer pathways, by employing stringent bioinformatics and systems biology methodologies. Given that IR can cause repair resistant lesions within a short DNA segment (a few nm), thereby augmenting the hazardous and toxic effects of radiation, we also investigated the possible implication of the most biologically important of those genes in comorbid non-neoplastic diseases through network integration, as well as their potential for predicting survival in cancer patients.

Take a Break to Repair: A Dip in the World of Double-Strand Break Repair Mechanisms Pointing the Gaze on Archaea

All organisms have evolved many DNA repair pathways to counteract the different types of DNA damages. The detection of DNA damage leads to distinct cellular responses that bring about cell cycle arrest and the induction of DNA repair mechanisms. In particular, DNA double-strand breaks (DSBs) are extremely toxic for cell survival, that is why cells use specific mechanisms of DNA repair in order to maintain genome stability. The choice among the repair pathways is mainly linked to the cell cycle phases. Indeed, if it occurs in an inappropriate cellular context, it may cause genome rearrangements, giving rise to many types of human diseases, from developmental disorders to cancer. Here, we analyze the most recent remarks about the main pathways of DSB repair with the focus on homologous recombination. A thorough knowledge in DNA repair mechanisms is pivotal for identifying the most accurate treatments in human diseases.

Tools for Decoding Ubiquitin Signaling in DNA Repair

The maintenance of genome stability requires dedicated DNA repair processes and pathways that are essential for the faithful duplication and propagation of chromosomes. These DNA repair mechanisms counteract the potentially deleterious impact of the frequent genotoxic challenges faced by cells from both exogenous and endogenous agents. Intrinsic to these mechanisms, cells have an arsenal of protein factors that can be utilised to promote repair processes in response to DNA lesions. Orchestration of the protein factors within the various cellular DNA repair pathways is performed, in part, by post-translational modifications, such as phosphorylation, ubiquitin, SUMO and other ubiquitin-like modifiers (UBLs). In this review, we firstly explore recent advances in the tools for identifying factors involved in both DNA repair and ubiquitin signaling pathways. We then expand on this by evaluating the growing repertoire of proteomic, biochemical and structural techniques available to further understand the mechanistic basis by which these complex modifications regulate DNA repair. Together, we provide a snapshot of the range of methods now available to investigate and decode how ubiquitin signaling can promote DNA repair and maintain genome stability in mammalian cells.