Oncogenic potential of SARS-CoV-2-targeting hallmarks of cancer pathways.

The 2019 outbreak of SARS-CoV-2 has caused a major worldwide health crisis with high rates of morbidity and death. Interestingly, it has also been linked to cancer, which begs the issue of whether it plays a role in carcinogenesis. Recent studies have revealed various mechanisms by which SARS-CoV-2 can influence oncogenic pathways, potentially promoting cancer development. The virus encodes several proteins that alter key signaling pathways associated with cancer hallmarks. Unlike classical oncogenic viruses, which transform cells through viral oncogenes or by activating host oncogenes, SARS-CoV-2 appears to promote tumorigenesis by inhibiting tumor suppressor genes and pathways while activating survival, proliferation, and inflammation-associated signaling cascades. Bioinformatic analyses and experimental studies have identified numerous interactions between SARS-CoV-2 proteins and cellular components involved in cancer-related processes. This review explores the intricate relationship between SARS-CoV-2 infection and cancer, focusing on the regulation of key hallmarks driving initiation, promotion and progression of cancer by viral proteins. By elucidating the underlying mechanisms driving cellular transformation, the potential of SARS-CoV-2 as an oncovirus is highlighted. Comprehending these interplays is essential to enhance our understanding of COVID-19 and cancer biology and further formulating strategies to alleviate SARS-CoV-2 influence on cancer consequences.

Integrating Machine Learning with Multi-Omics Technologies in Geroscience: Towards Personalized Medicine.

Aging is a fundamental biological process characterized by a progressive decline in physiological functions and an increased susceptibility to diseases. Understanding aging at the molecular level is crucial for developing interventions that could delay or reverse its effects. This review explores the integration of machine learning (ML) with multi-omics technologies-including genomics, transcriptomics, epigenomics, proteomics, and metabolomics-in studying the molecular hallmarks of aging to develop personalized medicine interventions. These hallmarks include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Using ML to analyze big and complex datasets helps uncover detailed molecular interactions and pathways that play a role in aging. The advances of ML can facilitate the discovery of biomarkers and therapeutic targets, offering insights into personalized anti-aging strategies. With these developments, the future points toward a better understanding of the aging process, aiming ultimately to promote healthy aging and extend life expectancy.

A summer course in cancer for high school students-an update on lessons taught and lessons learned.

BACKGROUND: Previous graduate students and postdoctoral associates from the University of Florida Health Cancer Center, in partnership with the University of Florida Student Science Training Program, implemented a cooperative learning curriculum, providing high school students with a broad overview of cancer topics over six weeks over the summer. To address discussions necessitated by the COVID-19 pandemic on student autonomy, we report lessons learned and outcomes of a cancer biology and therapeutic curriculum modified for a collaborative learning environment. METHODS: This pre-post longitudinal observational study conducted in 2023 on a cancer biology and therapeutics course evaluated students' knowledge retention and general awareness and opinions in cancer research. A structured survey was employed for data collection, using learning assessment surveys and the Likert scale ranging from 1 to 10, with 10 being highly likely. RESULTS: Student performance tracked over a 7-year period indicated consistency in performance between years. Post-assessment analysis revealed significant improvements in student benchmark understanding, notably in their ability to define cancer in one sentence (p = 0.0407), identify cancer therapies (p = 0.0040), and recognize cancer hallmarks (p < 0.0001). An increased trend in median response to the likelihood of pursuing cancer research (p = 0.8793) and the possibility of pursuing cancer research (p = 0.4874) were also observed, although not statistically significant. Moreover, feedback from participating students indicated that "the educational activities at the end of class (e.g., escape room, case studies)" and "learning about cancer and getting to work in groups…" the curriculum fostered a positive educational learning environment. CONCLUSION: Students generally retained the course material presented and upheld a positive perception of the course. Incorporating opportunities for peer-to-peer learning, especially when introducing or discussing complex issues like cancer, may benefit student autotomy.

Membrane potential: A new hallmark of cancer.

Cancer remains a complex and multifaceted disease, characterized by a myriad of molecular and cellular alterations that collectively drive tumorigenesis and progression. Hanahan and Weinberg's concept of cancer hallmarks has offered a framework for comprehending the various but related aspects of cancer biology. Initially defined as a set of six hallmarks, further investigation has added more characteristics to this list that also contribute to the malignant phenotype. Changes in cellular energetics, proliferative signaling, and resistance to cell death are three of these hallmarks that have been thoroughly investigated and described. But new discoveries in the field of cancer biology have brought attention to the importance of another aspect of the biology of cancer: the dysregulation of membrane potential.

Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis.

Background: The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer. Methods: Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis. Results: The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network. Conclusion: The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.

Targeting Cancer Hallmarks Using Selected Food Bioactive Compounds: Potentials for Preventive and Therapeutic Strategies.

Cancer continues to be a prominent issue in healthcare systems, resulting in approximately 9.9 million fatalities in 2020. It is the second most common cause of death after cardiovascular diseases. Although there are difficulties in treating cancer at both the genetic and phenotypic levels, many cancer patients seek supplementary and alternative medicines to cope with their illness, relieve symptoms, and reduce the side effects of cytotoxic drug therapy. Consequently, there is an increasing emphasis on studying natural products that have the potential to prevent or treat cancer. Cancer cells depend on multiple hallmarks to secure survival. These hallmarks include sustained proliferation, apoptosis inactivation, stimulation of angiogenesis, immune evasion, and altered metabolism. Several natural products from food were reported to target multiple cancer hallmarks and can be used as adjuvant interventions to augment conventional therapies. This review summarizes the main active ingredients in food that have anticancer activities with a comprehensive discussion of the mechanisms of action. Thymoquinone, allicin, resveratrol, parthenolide, Epigallocatechin gallate, and piperine are promising anticancer bioactive ingredients in food. Natural products discussed in this review provide a solid ground for researchers to provide effective anticancer functional food.

Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.

Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis. The pivotal roles of heat shock proteins in modulating the hallmarks of cancer through the activation or inhibition of various signaling pathways has been well documented. Therefore, this review provides an overview of the roles of heat shock proteins in vital biological processes from the perspective of the hallmarks of cancer and summarizes the small-molecule inhibitors that target heat shock proteins to regulate various cancer hallmarks. Moreover, we further discuss combination therapy strategies involving heat shock proteins and promising dual-target inhibitors to highlight the potential of targeting heat shock proteins for cancer treatment. In summary, this review highlights how targeting heat shock proteins could regulate the hallmarks of cancer, which will provide valuable information to better elucidate and understand the roles of heat shock proteins in oncology and the mechanisms of cancer occurrence and development and aid in the development of more efficacious and less toxic novel anticancer agents.

Adipose tissue senescence: Biological changes, hallmarks and therapeutic approaches.

Adipose tissue (AT), the largest energy storage reservoir and endocrine organ, plays a crucial role in regulating systemic energy metabolism. As one of the most vulnerable tissues during aging, the plasticity of AT is impaired. With age, AT undergoes redistribution, characterized by expansion of visceral adipose tissue (VAT) and reduction of peripheral subcutaneous adipose tissue (SAT). Additionally, age-related changes in AT include reduced adipogenesis of white adipocytes, decreased proliferation and differentiation capacity of mesenchymal stromal/stem cells (MSCs), diminished thermogenic capacity in brown/beige adipocytes, and dysregulation of immune cells. Specific and sensitive hallmarks enable the monitoring and evaluation of the biological changes associated with aging. In this study, we have innovatively proposed seven characteristic hallmarks of AT senescence, including telomere attrition, epigenetic alterations, genomic instability, mitochondrial dysfunction, disabled macroautophagy, cellular senescence, and chronic inflammation, which are intricately interconnected and mutually regulated. Finally, we discussed anti-aging strategies targeting AT, offering insights into mitigating or delaying metabolic disturbances caused by AT senescence.

High sugar diet promotes tumor progression paradoxically through aberrant upregulation of pepck1.

High dietary sugar (HDS), a contemporary dietary concern due to excessive intake of added sugars and carbohydrates, escalates the risk of metabolic disorders and concomitant cancers. However, the molecular mechanisms underlying HDS-induced cancer progression are not completely understood. We found that phosphoenolpyruvate carboxykinase 1 (PEPCK1), a pivotal enzyme in gluconeogenesis, is paradoxically upregulated in tumors by HDS, but not by normal dietary sugar (NDS), during tumor progression. Targeted knockdown of pepck1, but not pepck2, specifically in tumor tissue in Drosophila in vivo, not only attenuates HDS-induced tumor growth but also significantly improves the survival of Ras/Src tumor-bearing animals fed HDS. Interestingly, HP1a-mediated heterochromatin interacts directly with the pepck1 gene and downregulates pepck1 gene expression in wild-type Drosophila. Mechanistically, we demonstrated that, under HDS conditions, pepck1 knockdown reduces both wingless and TOR signaling, decreases evasion of apoptosis, reduces genome instability, and suppresses glucose uptake and trehalose levels in tumor cells in vivo. Moreover, rational pharmacological inhibition of PEPCK1, using hydrazinium sulfate, greatly improves the survival of tumor-bearing animals with pepck1 knockdown under HDS. This study is the first to show that elevated levels of dietary sugar induce aberrant upregulation of PEPCK1, which promotes tumor progression through altered cell signaling, evasion of apoptosis, genome instability, and reprogramming of carbohydrate metabolism. These findings contribute to our understanding of the complex relationship between diet and cancer at the molecular, cellular, and organismal levels and reveal PEPCK1 as a potential target for the prevention and treatment of cancers associated with metabolic disorders.

Immunologic mediators profile in COVID-19 convalescence.

SARS-CoV-2 caused the pandemic situation experienced since the beginning of 2020, and many countries faced the rapid spread and severe form of the disease. Mechanisms of interaction between the virus and the host were observed during acute phase, but few data are available when related to immunity dynamics in convalescents. We conducted a longitudinal study, with 51 healthy donors and 62 COVID-19 convalescent patients, which these had a 2-month follow-up after symptoms recovery. Venous blood sample was obtained from all participants to measure blood count, subpopulations of monocytes, lymphocytes, natural killer cells and dendritic cells. Serum was used to measure cytokines, chemokines, growth factors, anti-N IgG and anti-S IgG/IgM antibodies. Statistic was performed by Kruskal-Wallis test, and linear regression with days post symptoms and antibody titers. All analysis had confidence interval of 95%. Less than 35% of convalescents were anti-S IgM+, while more than 80% were IgG+ in D30. Anti-N IgG decreased along time, with loss of seroreactivity of 13%. Eosinophil count played a distinct role on both antibodies during all study, and the convalescence was orchestrated by higher neutrophil-to-lymphocyte ratio and IL-15, but initial stages were marked by increase in myeloid DCs, B1 lymphocytes, inflammatory and patrolling monocytes, G-CSF and IL-2. Later convalescence seemed to change to cytotoxicity mediated by T lymphocytes, plasmacytoid DCs, VEGF, IL-9 and CXCL10. Anti-S IgG antibodies showed the longest perseverance and may be a better option for diagnosis. The inflammatory pattern is yet present on initial stage of convalescence, but quickly shifts to a reparative dynamic. Meanwhile eosinophils seem to play a role on anti-N levels in convalescence, although may not be the major causative agent. We must highlight the importance of immunological markers on acute clinical outcomes, but their comprehension to potentialize adaptive system must be explored to improve immunizations and further preventive policies.

The Impact of Aging on HIV-1-related Neurocognitive Impairment.

Depending on the population studied, HIV-1-related neurocognitive impairment is estimated to impact up to half the population of people living with HIV (PLWH) despite the availability of combination antiretroviral therapy (cART). Various factors contribute to this neurocognitive impairment, which complicates our understanding of the molecular mechanisms involved. Biological aging has been implicated as one factor possibly impacting the development and progression of HIV-1-related neurocognitive impairment. This is increasingly important as the life expectancy of PLWH with virologic suppression on cART is currently projected to be similar to that of individuals not living with HIV. Based on our increasing understanding of the biological aging process on a cellular level, we aim to dissect possible interactions of aging- and HIV-1 infection-induced effects and their role in neurocognitive decline. Thus, we begin by providing a brief overview of the clinical aspects of HIV-1-related neurocognitive impairment and review the accumulating evidence implicating aging in its development (Part I). We then discuss potential interactions between aging-associated pathways and HIV-1-induced effects at the molecular level (Part II).

Exploring the Geroprotective Potential of Nutraceuticals.

Aging is the result of the accumulation of a wide variety of molecular and cellular damages over time, meaning that "the more damage we accumulate, the higher the possibility to develop age-related diseases". Therefore, to reduce the incidence of such diseases and improve human health, it becomes important to find ways to combat such damage. In this sense, geroprotectors have been suggested as molecules that could slow down or prevent age-related diseases. On the other hand, nutraceuticals are another set of compounds that align with the need to prevent diseases and promote health since they are biologically active molecules (occurring naturally in food) that, apart from having a nutritional role, have preventive properties, such as antioxidant, anti-inflammatory and antitumoral, just to mention a few. Therefore, in the present review using the specialized databases Scopus and PubMed we collected information from articles published from 2010 to 2023 in order to describe the role of nutraceuticals during the aging process and, given their role in targeting the hallmarks of aging, we suggest that they are potential geroprotectors that could be consumed as part of our regular diet or administered additionally as nutritional supplements.

Molecular Morbidity Score-Can MicroRNAs Assess the Burden of Disease?

Multimorbidity refers to the presence of two or more chronic diseases and is associated with adverse outcomes for patients. Factors such as an ageing population have contributed to a rise in prevalence of multimorbidity globally; however, multimorbidity is often neglected in clinical guidelines. This is largely because patients with multimorbidity are systematically excluded from clinical trials. Accordingly, there is an urgent need to develop novel biomarkers and methods of prognostication for this cohort of patients. The hallmarks of ageing are now thought to potentiate the pathogenesis of multimorbidity. MicroRNAs are small, regulatory, noncoding RNAs which have been implicated in the pathogenesis and prognostication of numerous chronic diseases; there is a substantial body of evidence now implicating microRNA dysregulation with the different hallmarks of ageing in the aetiology of chronic diseases. This article proposes using the hallmarks of ageing as a framework to develop a panel of microRNAs to assess the prognostic burden of multimorbidity. This putative molecular morbidity score would have many potential applications, including assessing the efficacy of clinical interventions, informing clinical decision making and facilitating wider inclusion of patients with multimorbidity in clinical trials.

Detailing the biomedical aspects of geroscience by molecular data and large-scale "deep" bioinformatics analyses.

As scientists investigated the molecular mechanisms of the biology of aging, they discovered that these are malleable and can enhance healthy longevity by intervening in the drivers of aging, which are leading to disease, dysfunction and death. These exciting observations gave birth to the field of geroscience. As the mechanisms of aging affect almost all mechanisms of life, detailed molecular mechanistic knowledge must be gained or expanded by considering and integrating as many types of data as possible, from genes and transcripts to socioenvironmental factors. Such a large-scale integration of large amounts of data will in turn profit from "deep" bioinformatics analyses that provide insights beyond contextualizing and interpreting the data in the light of knowledge from databases such as the Gene Ontology. The authors suggest that "deep" bioinformatics, employing methods based on artificial intelligence, will be a key ingredient of future analyses.

Interleukin 4 and cancer resistance in glioblastoma multiforme.

In this review, the author highlights the role of IL4 in mitigating all the "hallmarks" of cancer growth and resistance to current immunotherapy, providing a framework for its role in GBM as well as guideline for future treatment regimens. This review is organized around six strategies by which IL4 contributes to the immune resistance seen in GBM: (i) apoptosis evasion, (ii) self-sufficiency in growth signals, (iii) insensitivity to anti-growth signals, (iv) invasion and metastasis, (v) limitless replicative potential, (vi) sustained angiogenesis.

The multifaceted roles of circular RNAs in cancer hallmarks: From mechanisms to clinical implications.

Circular RNAs (circRNAs) represent a distinct class of covalently closed RNA species lacking conventional 5' to 3' polarity. Derived predominantly from pre-mRNA transcripts of protein-coding genes, circRNAs arise through back-splicing events of exon-exon or exon-intron junctions. They exhibit tissue- and cell-specific expression patterns and play crucial roles in regulating fundamental cellular processes such as cell cycle dynamics, proliferation, apoptosis, and differentiation. CircRNAs modulate gene expression through a plethora of mechanisms at epigenetic, transcriptional, and post-transcriptional levels, and some can even undergo translation into functional proteins. Recently, aberrant expression of circRNAs has emerged as a significant molecular aberration within the intricate regulatory networks governing hallmarks of cancer. The tumor-specific expression patterns and remarkable stability of circRNAs have profound implications for cancer diagnosis, prognosis, and therapy. This review comprehensively explores the multifaceted roles of circRNAs across cancer hallmarks in various tumor types, underscoring their growing significance in cancer diagnosis and therapeutic interventions. It also details strategies for leveraging circRNA-based therapies and discusses the challenges in using circRNAs for cancer management, emphasizing the need for further research to overcome these obstacles.

Trajectories of cardiovascular ageing - from molecular mechanisms to clinical implementation.

Due to its peculiar structure and function, the cardiovascular system is particularly vulnerable to the detrimental effects of ageing. Current knowledge about the molecular mechanisms of ageing revealed the processes actively promoting ageing, e.g. progressive telomeres shortening, and the mechanisms opposing it, e.g. endogenous production of antioxidant substances. This knowledge can be used to measure biological age at a cellular and molecular level and to interfere with it by pharmacological or non-pharmacological interventions. Biological ageing is determined by the simultaneous occurrence of independent hallmarks, which encompass a wide range of biological processes, from genomic changes to systemic inflammation and dysbiosis. This narrative review will summarize the role of ageing hallmarks in the cardiovascular system, how they can be measured and what are the possible interventions to counteract their effects.

A Molecular Hypothesis on Malignant Transformation of Oral Lichen Planus: A Systematic Review and Meta-Analysis of Cancer Hallmarks Expression in This Oral Potentially Malignant Disorder.

We aimed to qualitatively and quantitatively analyze, through a systematic review and meta-analysis, the current evidence on the differential expression of the hallmarks of cancer in oral lichen planus (OLP) samples, in order to know the earliest molecular mechanisms that could be involved in the malignant transformation of this oral potentially malignant disorder. We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2023. We evaluated the methodological quality of studies and carried out meta-analyses to fulfill our objectives. Inclusion criteria were met by 110 primary-level studies, with 7065 OLP samples, in which the expression of 104 biomarkers were analyzed through immunohistochemistry. Most OLP samples showed sustained cell proliferation signaling (65.48%, 95%CI = 51.87-78.02), anti-apoptotic pathways (55.93%, 95%CI = 35.99-75.0), genome instability (48.44%, 95%CI = 13.54-84.19), and tumor-promoting inflammation events (83.10%, 95%CI = 73.93-90.74). Concurrently, OLP samples also harbored tumor growth suppressor mechanisms (64.00%, 95%CI = 53.27-74.12). In conclusion, current evidence indicates that molecular mechanisms promoting hyperproliferative signaling, an antiapoptotic state with genomic instability, and an escape of epithelial cells from immune destruction, are developed in LP-affected oral mucosa. It is plausible that these events are due to the actions exerted by the chronic inflammatory infiltrate. Malignant transformation appears to be prevented by tumor suppressor genes, which showed consistent upregulation in OLP samples.

Cell-cell fusion in cancer: The next cancer hallmark?

In this review, we consider the role of cell-cell fusion in cancer development and progression through an evolutionary lens. We begin by summarizing the origins of fusion proteins (fusogens), of which there are many distinct classes that have evolved through convergent evolution. We then use an evolutionary framework to highlight how the persistence of fusion over generations and across different organisms can be attributed to traits that increase fitness secondary to fusion; these traits map well to the expanded hallmarks of cancer. By studying the tumor microenvironment, we can begin to identify the key selective pressures that may favor higher rates of fusion compared to healthy tissues. The paper concludes by discussing the increasing number of research questions surrounding fusion, recommendations for how to answer them, and the need for a greater interest in exploring cell fusion and evolutionary principles in oncology moving forward.

Effects of Ginger (Zingiber officinale) on the Hallmarks of Aging.

Ginger (Zingiber officinale Roscoe) is broadly used as a traditional remedy and food ingredient, and numerous preclinical and clinical studies have demonstrated health benefits in a range of age-related disorders. Moreover, longevity-promoting effects have been demonstrated in several (preclinical) research models. With this work, we aimed to comprehensively review the reported effects of ginger and its bioactive constituents on the twelve established hallmarks of aging, with the ultimate goal of gaining a deeper understanding of the potential for future interventions in the area of longevity-extension and counteracting of aging-related diseases. The reviewed literature supports the favorable effects of ginger and some of its constituents on all twelve hallmarks of aging, with a particularly high number of animal research studies indicating counteraction of nutrient-sensing dysregulations, mitochondrial dysfunction, chronic inflammation, and dysbiosis. On this background, validation in human clinical trials is still insufficient or is entirely missing, with the exception of some studies indicating positive effects on deregulated nutrient-sensing, chronic inflammation, and dysbiosis. Thus, the existing body of literature clearly supports the potential of ginger to be further studied in clinical trials as a supplement for the promotion of both lifespan and health span.