Exogenous Stressors Research Articles

A note on the nomenclatural representation of plant transcription factors, and deviations thereof

Abstract Plant transcription factors (TFs) are integral proteins associated with gene transcription. That ability arises after TFs bind to specific DNA sequences, such as promoters, responding positively or negatively to a multitude of endogenous and exogenous factors or stressors. For this reason, in plants, the vast majority of TFs are associated with growth, development, and responses to biotic and abiotic stresses. As is commonly known, the genes coding for TFs are written in uppercase italics, whereas the resulting proteins are written in lowercase, such as OsWRKY28 and OsWRKY28, respectively for a member of the WRKY TF family in rice (Oryza sativa L.). However, despite the existence of some conventions for the nomenclature of TFs, some deviation from these norms has been observed in the literature. Several cases are highlighted, primarily related to NAC TFs. These cases emphasize the need for stricter quality control of literature pertaining to the nomenclature of plant TFs.

The Mediating Role of Neighborhood Networks on Long‐Term Trajectories of Subjective Well‐Being After Covid‐19

We investigate the trajectories of people’s subjective well‐being, measured as their overall life satisfaction at five points in time before, during, and after Covid‐19 in Switzerland. Using sequence analysis and hierarchical clustering, we identify three groups of typical trajectories. About half of all respondents experienced a decline in well‐being right after the first lockdown and subsequent recovery to high, pre‐pandemic levels. A quarter consistently reports very high satisfaction throughout all five waves, and another quarter experienced declining well‐being since the outbreak of the pandemic. As a second contribution, we then demonstrate how improving relations with neighbors increases the likelihood of recovering from the negative impact of the pandemic on subjective well‐being. This effect is largely constant across social groups. Conceptualizing vulnerability as the extent to which social groups with different endowments (e.g., financial situation or individual social networks) cope differently with (exogenous) stressors, we further find slightly more pronounced positive effects of improving neighborly relations during the pandemic for more vulnerable people in terms of household finances and education. Moreover, being able to count on emotional support from neighbors and friends prior to the pandemic generally guarded against experiencing declining well‐being. Meanwhile, people with less financial means, poorer health, and less support from friends and neighbors are also more likely to be in the trajectory cluster of declining well‐being.

Interactions of multiple stressors on the Bombay-duck Harpadon nehereus population in a complex estuarine ecosystem

In an era marked by unprecedented anthropogenic change, marine systems are increasingly subjected to interconnected and dynamic external stressors, which profoundly reshape the behavior and resilience of marine ecological components. Nevertheless, despite widespread recognition of the significance of stressor interactions, there persist notable knowledge deficits in quantifying their interactions and the specific biological consequences that result. To bridge this crucial gap, this research detected and examined the causal relationships between five key exogenous stressors in a complex estuarine ecosystem. Furthermore, a Bayesian Hierarchical Spatio-temporal modeling framework was proposed to quantitatively evaluate the distinct, interactive, and globally sensitive effects of multiple stressors on the population dynamics of a crucial fish species: Harpadon nehereus. The results showed that interactions were detected between fisheries pressure (FP), the Pacific Decadal Oscillation index (PDO), runoff volume (RV), and sediment load (SL), with five of these interactions producing significant synergistic effects on H. nehereus biomass. The SL*PDO and RV*PDO interactions had positive synergistic effects, albeit through differing processes. The former interaction amplified the individual effects of each stressor, while the latter reversed the direction of the original impact. Indeed overall, the synergistic effect of multiple stressors was not favorable, with FP in particular posing the greatest threat to H. nehereus population. This threat was more pronounced at high SL or negative PDO phases. Therefore, local management efforts aimed at addressing multiple stressors and protecting resources should consider the findings. Additionally, although the velocity of climate change (VoCC) failed to produce significant interactions, changes in this stressor had the most sensitive impacts on the response of H. nehereus population. This research strives to enhance the dimensionality, generalizability, and flexibility of the quantification framework for marine multi-stressor interactions, aiming to foster broader research collaboration and jointly tackle the intricate pressures facing marine ecosystems.

Full-length direct RNA sequencing uncovers stress-granule dependent RNA decay upon cellular stress.

Cells react to stress by triggering response pathways, leading to extensive alterations in the transcriptome to restore cellular homeostasis. The role of RNA metabolism in shaping the cellular response to stress is vital, yet the global changes in RNA stability under these conditions remain unclear. In this work, we employ direct RNA sequencing with nanopores, enhanced by 5' end adaptor ligation, to comprehensively interrogate the human transcriptome at single-molecule and nucleotide resolution. By developing a statistical framework to identify robust RNA length variations in nanopore data, we find that cellular stress induces prevalent 5' end RNA decay that is coupled to translation and ribosome occupancy. Unlike typical RNA decay models in normal conditions, we show that stress-induced RNA decay is dependent on XRN1 but does not depend on deadenylation or decapping. We observed that RNAs undergoing decay are predominantly enriched in the stress granule transcriptome while inhibition of stress granule formation via genetic ablation of G3BP1 and G3BP2 rescues RNA length. Our findings reveal RNA decay as a key determinant of RNA metabolism upon cellular stress and dependent on stress-granule formation.

Detection of DNA Breaks in Dividing Human Cells by Neutral Comet Assay.

DNA replication is constantly challenged by a wide variety of endogenous and exogenous stressors that can damage DNA. Such lesions encountered during genome duplication can stall replisomes and convert replication forks into double-strand breaks. If left unrepaired, these toxic DNA breaks can trigger chromosomal rearrangements, leading to heightened genome instability and an increased likelihood of cellular transformation. Additionally, cancer cells exhibit persistent replication stress, making the targeting of replication fork vulnerabilities in tumor cells an attractive strategy for chemotherapy. A highly versatile and powerful technique to study DNA breaks during replication is the comet assay. This gel electrophoresis technique reliably detects the induction and repair of DNA breaks at the single-cell level. Herein, a protocol is outlined that allows investigators to measure the extent of DNA damage in mitotically dividing human cells using fork-stalling agents across multiple cell types. Coupling this with automated comet scoring facilitates rapid analysis and enhances the reliability in studying induction of DNA breaks.

Frailty in Oncology: Updated Recommendations for Clinical Practice

Frailty is a clinical condition associated with aging and resulting in increased risk of adverse outcomes upon exogenous or endogenous stressors. In oncology, cancer treatment itself can be a stressor event. In older cancer patients, frailty therefore not only enhances the probability of age-related health events such as institutionalization or falls, but also of treatment complications such as toxicity and interruption or discontinuation of therapy. As demonstrated by recent randomized-controlled trials conducted in older cancer patients receiving systemic treatment, the evaluation of frailty by geriatric assessment (GA) followed by an adjustment of the oncological therapy as well as targeted frailty interventions help to improve cancer treatment tolerability and feasibility. Based on these data, the American Society of Clinical Oncology (ASCO) updated the clinical practice guidelines for the assessment and management of vulnerabilities in older adults receiving systemic cancer therapy. The guideline recommends the use of a new GA-tool named 'practical geriatric assessment' (PGA) to foster the implementation of GA-based frailty assessment and management in routine cancer care. This article describes the background and key aspects of these recent advances.

Rapid P-TEFb-dependent transcriptional reorganization underpins the glioma adaptive response to radiotherapy

Dynamic regulation of gene expression is fundamental for cellular adaptation to exogenous stressors. P-TEFb-mediated pause-release of RNA polymerase II (Pol II) is a conserved regulatory mechanism for synchronous transcriptional induction in response to heat shock, but this pro-survival role has not been examined in the applied context of cancer therapy. Using model systems of pediatric high-grade glioma, we show that rapid genome-wide reorganization of active chromatin facilitates P-TEFb-mediated nascent transcriptional induction within hours of exposure to therapeutic ionizing radiation. Concurrent inhibition of P-TEFb disrupts this chromatin reorganization and blunts transcriptional induction, abrogating key adaptive programs such as DNA damage repair and cell cycle regulation. This combination demonstrates a potent, synergistic therapeutic potential agnostic of glioma subtype, leading to a marked induction of tumor cell apoptosis and prolongation of xenograft survival. These studies reveal a central role for P-TEFb underpinning the early adaptive response to radiotherapy, opening avenues for combinatorial treatment in these lethal malignancies.

Identification and characterization of STAT family in silver pomfret (Pampus argenteus) involved in different exogenous stresses

Members of the Signal Transducer and Activator of Transcription (STAT) family function pivotally as transcriptional activators integral to the modulation of inflammatory responses. The aquaculture of silver pomfret is frequently compromised by the imposition of exogenous stressors, which include thermal fluctuations, notably low-temperatures, diminished oxygen levels, and the onslaught of bacterial pathogens. Notwithstanding the critical impact of these stressors, the scientific literature presents a notable gap in our understanding of the STAT pathway's role in the silver pomfret's adaptive response mechanisms. To address this lacuna, we identified stat genes in the silver pomfret—denominated as Pastat1, Pastat2, Pastat3, Pastat4, and Pastat5—through a thorough and systematic bioinformatics analysis. Further scrutiny of the gene configurations and constituent motifs has elucidated that STAT proteins possess analogous structural frameworks and exhibit significant evolutionary preservation. Subsequently, the expression patterns of five stat genes were verified by RT-qPCR in twelve different tissues and four growth periods in healthy fish, showing that the expression of Pastat genes was temporally and spatially specific, with most of the stat genes expressed at higher levels in the spleen, following muscle, gill, and liver. Transcriptomic analysis of exposure to exogenous stressors, specifically formaldehyde and low-temperature conditions, elucidated that Pastat1 and Pastat2 genes exhibited a heightened sensitivity to these environmental challenges. RT-qPCR assays demonstrated a marked alteration in the expression profiles of jak1 and Pastat gene suites in PaS upon prolonged bacterial infection subsequent to these exogenous insults. Moreover, the gene expression of the downstream effectors involved in innate immunity and apoptosis displayed marked deviations. This study additionally elucidated the Pastat gene family's role in modulating the innate immune response and apoptotic regulation within the silver pomfret during exogenous stressors and subsequent pathogenic incursions.

Building an Understanding of Proteostasis in Reproductive Cells: The Impact of Reactive Carbonyl Species on Protein Fate.

Significance: Stringent regulation of protein homeostasis pathways, under both physiological and pathological conditions, is necessary for the maintenance of proteome fidelity and optimal cell functioning. However, when challenged by endogenous or exogenous stressors, these proteostasis pathways can become dysregulated with detrimental consequences for protein fate, cell survival, and overall organism health. Most notably, there are numerous somatic pathologies associated with a loss of proteostatic regulation, including neurodegenerative disorders, type 2 diabetes, and some cancers. Recent Advances: Lipid oxidation-derived reactive carbonyl species (RCS), such as 4-hydroxynonenal (4HNE) and malondialdehyde, are relatively underappreciated purveyors of proteostatic dysregulation, which elicit their effects via the nonenzymatic post-translational modification of proteins. Emerging evidence suggests that a subset of germline proteins can serve as substrates for 4HNE modification. Among these, prevalent targets include succinate dehydrogenase, heat shock protein A2 and A-kinase anchor protein 4, all of which are intrinsically associated with fertility. Critical Issues: Despite growing knowledge in this field, the RCS adductomes of spermatozoa and oocytes are yet to be comprehensively investigated. Furthermore, the manner by which RCS-mediated adduction impacts protein fate and drives cellular responses, such as protein aggregation, requires further examination in the germline. Given that RCS-protein adduction has been attributed a role in infertility, there has been sparked research investment into strategies to prevent lipid peroxidation in germ cells. Future Directions: An increased depth of knowledge regarding the mechanisms and substrates of RCS-mediated protein modification in reproductive cells may reveal important targets for the development of novel therapies to improve fertility and pregnancy outcomes for future generations.

Ethosomes for Curcumin and Piperine Cutaneous Delivery to Prevent Environmental-Stressor-Induced Skin Damage.

Diesel particulate matter is one of the most dangerous environmental stressors affecting human health. Many plant-derived compounds with antioxidant and anti-inflammatory properties have been proposed to protect the skin from pollution damage. Curcumin (CUR) has a plethora of pharmacological activities, including anticancer, antimicrobial, anti-inflammatory and antioxidant. However, it has low bioavailability due to its difficult absorption and rapid metabolism and elimination. CUR encapsulation in nanotechnological systems and its combination with biopotentiators such as piperine (PIP) can improve its pharmacokinetics, stability and activity. In this study, ethosomes (ETs) were investigated for CUR and PIP delivery to protect the skin from damage induced by diesel particulate matter. ETs were produced by different strategies and characterized for their size distribution by photon correlation spectroscopy, for their morphology by transmission electron microscopy, and for their drug encapsulation efficiency by high-performance liquid chromatography. Franz cells enabled us to evaluate in vitro the drug diffusion from ETs. The results highlighted that ETs can promote the skin permeation of curcumin. The studies carried out on their antioxidant activity demonstrated an increase in the antioxidant power of CUR using a combination of CUR and PIP separately loaded in ETs, suggesting their possible application for the prevention of skin damage due to exogenous stressors. Ex vivo studies on human skin explants have shown the suitability of drug-loaded ETs to prevent the structural damage to the skin induced by diesel engine exhaust exposure.

A single case study on Ekakustha (Scalp Psoriasis) with Ayurvedic Management

Ekakustha (Psoriasis) is non-infectious chronic inflammatory disease of skin characterized by well-defined erythematous plaques with silvery scale which have a preference for extensor surface and scalp and by chronic fluctuating course. The disease not only disturbs the patient physically but also interrupts the mental and social health of the patient. Psoriasis occurs when the immune system mistakes the skin cells as pathogens and sends out faulty signals that speed up the growth cycle of skin tissues of the body. Psoriasis is a multi-factorial disease that arises due to many factors such as genetic predisposition, local trauma, general illness, smoking, excessive alcohol, indigestion, and stress. According to Ayurveda vitiation of Vata and Kapha Dosha by dietary and lifestyle changes play a primitive role in the generation of chronic psoriasis. In addition to this, Ama, a variety of exogenous environmental stressors and genetic / epigenetic factors play a significant role in the pathogenesis of psoriasis. These vitiated Doshas with and without Ama, in turn, adversely affect the skin and blood tissues as well. So, in psoriasis Vata, Kapha, and Pitta / Rakta vitiation are major contributing pathological factors in its manifestation. Here a 32 years old male patient came with complain of Shiro Kandu (itching on scalp), Kesha Patana (Hair falling), Darunaka (Dandruff), Vibandh (Constipation). He was diagnosed with Ekakustha (psoriasis). All the symptoms were resolved in 2 months. Psoriasis patient can get benefits from Ayurveda treatment like Takra Dhara and Shaman Chikitsa.

The frail patient undergoing cardiac surgery: lessons learned and future perspectives.

Frailty is a geriatric condition characterized by the reduction of the individual's homeostatic reserves. It determines an increased vulnerability to endogenous and exogenous stressors and can lead to poor outcomes. It is an emerging concept in perioperative medicine, since an increasing number of patients undergoing surgical interventions are older and the traditional models of care seem to be inadequate to satisfy these patients' emerging clinical needs. Nowadays, the progressive technical and clinical improvements allow to offer cardiac operations to an older, sicker and frail population. For these reasons, a multidisciplinary team involving cardiac surgeons, clinical cardiologists, anesthesiologists, and geriatricians, is often needed to assess, select and provide tailored care to these high-risk frail patients to optimize clinical outcomes. There is unanimous agreement that frailty assessment may capture the individual's biological decline and the heterogeneity in risk profile for poor health-related outcomes among people of the same age. However, since commonly used preoperative scores for cardiac surgery fail to capture frailty, a specific preoperative assessment with dedicated tools is warranted to correctly recognize, measure and quantify frailty in these patients. On the contrary, pre-operative and post-operative interventions can reduce the risk of complications and support patient recovery promoting surgical resilience. Minimally invasive cardiac procedures aim to reduce surgical trauma and may be associated with better clinical outcome in this specific sub-group of high-risk patients. Among postoperative adverse events, the occurrence of delirium represents a risk factor for several unfavorable outcomes including mortality and subsequent cognitive decline. Its presence should be carefully recognized, triggering an adequate, evidence based, treatment. There is evidence, from several cross-section and longitudinal studies, that frailty and delirium may frequently overlap, with frailty serving both as a predisposing factor and as an outcome of delirium and delirium being a marker of a latent condition of frailty. In conclusion, frail patients are at increased risk to experience poor outcome after cardiac surgery. A multidisciplinary approach aimed to recognize more vulnerable individuals, optimize pre-operative conditions, reduce surgical invasivity and improve post-operative recovery is required to obtain optimal long-term outcome.

Iron Metabolism of the Skin: Recycling versus Release.

The skin protects the body against exogenous stressors. Its function is partially achieved by the permanent regeneration of the epidermis, which requires high metabolic activity and the shedding of superficial cells, leading to the loss of metabolites. Iron is involved in a plethora of important epidermal processes, including cellular respiration and detoxification of xenobiotics. Likewise, microorganisms on the surface of the skin depend on iron, which is supplied by the turnover of epithelial cells. Here, we review the metabolism of iron in the skin with a particular focus on the fate of iron in epidermal keratinocytes. The iron metabolism of the epidermis is controlled by genes that are differentially expressed in the inner and outer layers of the epidermis, establishing a system that supports the recycling of iron and counteracts the release of iron from the skin surface. Heme oxygenase-1 (HMOX1), ferroportin (SLC40A1) and hephaestin-like 1 (HEPHL1) are constitutively expressed in terminally differentiated keratinocytes and allow the recycling of iron from heme prior to the cornification of keratinocytes. We discuss the evidence for changes in the epidermal iron metabolism in diseases and explore promising topics of future studies of iron-dependent processes in the skin.

Modulation of NRF2: Biological Dualism in Cancer, Targets and Possible Therapeutic Applications.

Significance: The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) system is a master regulator of redox homeostasis and cell adaptation to a variety of exogenous and endogenous stressors. Accumulating evidence from the last decade indicates that the impairment of the redox balance leads to oxidative stress (OS), a common alteration occurring in many human acute and chronic inflammatory diseases, such as cancer, diabetes, neurodegeneration, and metabolic disorders, and aging. Recent Advances: Being located at the intersection of crucial signaling pathways, NRF2 can influence several cellular functions, which extend beyond the maintenance of the redox balance and include cellular metabolism, proteostasis, mitochondrial function and inflammation. For this reason, there is a growing interest in the pharmacologic manipulation of NRF2 for therapeutic purposes, which requires the accurate knowledge of the cell context and the specific time frame both of NRF2 activation and inhibition. This appears to be an important prerequisite and reflects the extreme complexity of the NRF2 signaling, characterized by an intrinsic dualism that mediates beneficial or detrimental effects even in the same biological process. Critical Issues: Of crucial importance will be to understand whether the NRF2 activity modulation might be exploited to exert beneficial outcomes in patients suffering from pathological conditions, in which the OS and the deregulation of inflammatory processes play a crucial role. Future Directions: In this review, we discuss the dual involvement of NRF2 in aging, neurodegeneration, metabolic diseases, long-COVID-19, and carcinogenesis and we present an overview of the most recent therapeutic modulators of NRF2, particularly emphasizing on those selected for clinical trials. Antioxid. Redox Signal. 40, 636-662.

Immunomodulatory, cyto-genotoxic, and growth regulatory effects of nerolidol on melon fruit fly, Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae)

Insects have evolved a robust immune system consisting of humoral and cellular branches and their orchestrated response enables insect to defend against exogenous stressors. Exploration of underlying immune mechanisms of insect pest under allelochemical stress can give us new insights on insect pest management. In this study, nerolidol, a plant sesquiterpene was evaluated for its insecticidal, growth regulatory, immunomodulatory, and cyto-genotoxic effects against melon fruit fly, Zeugodacus cucurbitae (Coquillett). First, second, and third instar larvae of Z. cucurbitae were fed on artificial diet containing different concentrations (5, 25, 125, 625, and 3125 ppm) of nerolidol. Results revealed a significant reduction in pupation and adult emergence as well as prolongation of developmental duration of treated larvae. Decline in growth indices showed remarkable growth inhibitory effects of nerolidol. Pupal weight and nutritional parameters viz. Larval weight gain, food assimilated, and mean relative growth rate declined after treatment. Immunological studies on second instar larvae depicted a drop in total hemocyte count and variations in proportions of plasmatocytes and granulocytes of LC30 and LC50 treated larvae. Phenoloxidase activity in nerolidol treated larvae initially increased but was suppressed after 72 h of treatment. The frequency of viable hemocytes decreased and that of apoptotic and necrotic hemocytes increased with both the lethal concentrations of nerolidol. Comet assay revealed a significant damage to DNA of hemocytes. The findings of the current study indicate that nerolidol exerts its insecticidal action through growth regulation, immunomodulation, and cyto-genotoxicity thus revealing its potential to be used as biopesticide against Z. cucurbitae.

Examination of stress–turnover relationship through perceived employee's exploitation at workplace

PurposeIn the purview of stress–turnover relationship, the present study aims to explore the endogenous and exogenous aspects of stress and employees' turnover intentions. Further, it also intends to evaluate the mediating role of perceived employee's exploitation between stressors and employee turnover intentions. For that matter, antecedents of stressors were identified and classified into endogenous and exogenous stressors: endogenous stressors relate to the employees' negative psychological contact within an organization and exogenous stressors are various macro-economic factors which have a considerable influence on employees' workplace behavior.Design/methodology/approachFor the purpose of this study, this study choses private school teachers as respondents working in the economically depressed state of India. Thus, data for the present study has been collected from 628 private school teachers of J&K (India) which were randomly selected. In order to ensure valid and reliable statistical inferences from the study, data collected has been validated using confirmatory factor analysis and hypothesis testing has been carried out through structural equation modeling.FindingsIt was found that both types of stressors were contributing negatively toward employee's psychological state resulting in undesirable employee organizational relationships manifested as turnover intentions among employees. Moreover, perceived employee's exploitation was found to intensify the relationship of employee turnover as a dependent variable regressed on endogenous, exogenous and occupational stress by fully mediating the stress–turnover intricacies.Research limitations/implicationsThe implications of the study include the identification of employees' stressor needs in order to gauge the understanding of the mechanism by which employees react to their environment and develop attitudes toward their jobs. The present study includes a small sample size obtained from private educational institutions only. Therefore, there is a need to take a geographically diverse sample that is inevitable for universal inferences and validity.Originality/valueVery little research has been conducted to explore endogenous, exogenous and unique stressors such as economic stress and perceived external opportunities which constitute the overall stress. Moreover, to the best of the authors’ knowledge, this is the first study which tests the model empirically that examines the effect of stress–turnover relationship through perceived employee's exploitation in the teaching and educational sector.

Institutional stability and change in environmental governance

Efforts to better understand what prevents institutions from changing to meet contemporary demands – or what facilitates the evolution of existing constructs to address new challenges – are of particular import and relevance to environmental governance. While the existing literature provides valuable conceptualisation and empirical evaluation of institutional stability and change, the lack of a consistent and holistic typology complicates the evaluation of institutions over time. In this article, we use a combined stability–change typology to assess the dominant modes of institutional change and stability over a multi-decadal timespan across three environmental governance systems – air quality governance in the US and China, and climate governance in the European Union. Across cases, we find that these modes are not mutually exclusive but can occur simultaneously, in concert or in conflict. We also find that observed patterns of change and stability are reflective of the social and political context in which systems operate, as well as the focus of the system itself (for example, localised air quality versus global climate change). Apart from providing a proof-of-concept analysis of institutional change and stability, our findings raise questions about the mechanisms underlying spatial and temporal patterns across identified modes. Indirectly, our findings also further highlight challenges to designing systems both resilient to exogenous stressors and capable of adapting to new situations. Our combined stability–change typology may help to advance understanding of whether and how such balancing has occurred in the past, thus facilitating future efforts to address contemporary challenges.

Role of melatonin as a protective antioxidant in the amelioration of oxidative stress mediated tissue injury: a new vision for futuristic medicine

Melatonin (N-acetyl-5-methoxy tryptamine) is ubiquitous in almost every creature; diatoms, bacteria, plants, and animals. During thecourse of organic evolution, melatonin (a pineal secretory product in vertebrates and mammals, including humans) never changed itsstructure and thus remain conserved as an ancient molecule in nature. Since discovery of the antioxidant properties of melatonin byDr. Dun-Xian Tan in 1993, its antioxidative efficacy in various situations of oxidative stress in plants, animals and humans has been wellestablished. It is clear that melatonin has evolved much earlier than other antioxidants. Ischaemic heart disease (IHD) and consequential myocardial infarction (MI) is a health problem of global concern and its ubiquitous prevalence is increasing worldwide annually. The involvement of oxidative stress in myocardial ischemia has long been recognized around the globe. Moreover, the prescribed medicines for cardiac tissue well-being sometimes became detrimental for gastric epithelium. Though endogenous gastric melatonin plays a protective role in offering protection to the entire gastric system, stress-mediated challenged melatonin level brings about threats to the gastric system. Mitigation of oxidative stress in the myocardium and gastric system as well, by antioxidants, may play an effective role in protection and the results of our studies carried out through several years have revealed that melatonin offers extensive protection toward the said systems when subjected to stress by physiological as well as synthetic molecules. Further, we have extrapolated our studies to check whether its protective action is extended toward erythrocytes, the first exposed cellular system to various exogenous and endogenous stressors. Moreover, melatonin was also found to exhibit cardio-protection when ISO aggravated high-fat diet-induced oxidative stress-mediated myocardial onslaught. Our studies revealed the association of a unique pathway in cardio-protection by melatonin. These findings further strengthen the role of melatonin as a cardio-protective antioxidant with no or minimal side effects, recognized globally and having immense future therapeutic relevance

Spatial mapping of the DNA adducts in cancer

DNA adducts and strand breaks are induced by various exogenous and endogenous agents. Accumulation of DNA damage is implicated in many disease processes, including cancer, aging, and neurodegeneration. The continuous acquisition of DNA damage from exogenous and endogenous stressors coupled with defects in DNA repair pathways contribute to the accumulation of DNA damage within the genome and genomic instability. While mutational burden offers some insight into the level of DNA damage a cell may have experienced and subsequently repaired, it does not quantify DNA adducts and strand breaks. Mutational burden also infers the identity of the DNA damage. With advances in DNA adduct detection and quantification methods, there is an opportunity to identify DNA adducts driving mutagenesis and correlate with a known exposome. However, most DNA adduct detection methods require isolation or separation of the DNA and its adducts from the context of the nuclei. Mass spectrometry, comet assays, and other techniques precisely quantify lesion types but lose the nuclear context and even tissue context of the DNA damage. The growth in spatial analysis technologies offers a novel opportunity to leverage DNA damage detection with nuclear and tissue context. However, we lack a wealth of techniques capable of detecting DNA damage in situ. Here, we review the limited existing in situ DNA damage detection methods and examine their potential to offer spatial analysis of DNA adducts in tumors or other tissues. We also offer a perspective on the need for spatial analysis of DNA damage in situ and highlight Repair Assisted Damage Detection (RADD) as an in situ DNA adduct technique with the potential to integrate with spatial analysis and the challenges to be addressed.

The Role of Oxidative Stress and Cellular Senescence in the Pathogenesis of Metabolic Associated Fatty Liver Disease and Related Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) represents a worryingly increasing cause of malignancy-related mortality, while Metabolic Associated Fatty Liver Disease (MAFLD) is going to become its most common cause in the next decade. Understanding the complex underlying pathophysiology of MAFLD-related HCC can provide opportunities for successful targeted therapies. Of particular interest in this sequela of hepatopathology is cellular senescence, a complex process characterised by cellular cycle arrest initiated by a variety of endogenous and exogenous cell stressors. A key biological process in establishing and maintaining senescence is oxidative stress, which is present in multiple cellular compartments of steatotic hepatocytes. Oxidative stress-induced cellular senescence can change hepatocyte function and metabolism, and alter, in a paracrine manner, the hepatic microenvironment, enabling disease progression from simple steatosis to inflammation and fibrosis, as well as HCC. The duration of senescence and the cell types it affects can tilt the scale from a tumour-protective self-restricting phenotype to the creator of an oncogenic hepatic milieu. A deeper understanding of the mechanism of the disease can guide the selection of the most appropriate senotherapeutic agent, as well as the optimal timing and cell type targeting for effectively combating HCC.