Search Results (1,074)

An open question in radiobiology concerns whether low doses of radiation are harmful or if cells are able to tolerate such exposure with minimal or no disruption. This issue is relevant for evaluating public health risks associated with the increasing number of medical computed tomography (CT) diagnostic procedures. This study evaluated the impact of CT scan-level exposure on human adipose mesenchymal stem cells (hMSCs) by measuring DNA damage responses (γH2AX, 53BP1, pATM foci), proliferation (Ki-67), senescence (β-galactosidase), and multiple gene expressions. Responses to one or five CT exposures were compared to a 2 Gy X-ray dose at intervals from 1 h to 10 passages post-irradiation. It was shown that CT scan briefly increased DNA damage markers but showed no significant long-term effects. A high dose of 2 Gy X-ray exposure caused sustained DNA damage, decreased proliferation, increased senescence, and significant changes in hundreds of genes even after several cell generations. After a single CT exposure, gene expression changes were minimal, while high-dose exposure led to strong activation of DNA repair and stress response pathways. Five CT scans caused a slight activation of LIF and HSPA1B genes, but these effects were minor compared to the high-dose group. All detected effects from CT scans were not observed by ten cell passages, whereas high-dose effects persisted. In conclusion, typical CT scan exposures have only short-term, mild effects on hMSCs, while high-dose radiation causes lasting cellular and genetic changes. Full article

Radioactive wastewater generated from nuclear energy, medical, and industrial sectors poses persistent ecological and health risks, necessitating the development of safe and sustainable treatment strategies. Compared with conventional physicochemical approaches, bioremediation using radiation-resistant bacteria (RRB) provides distinct advantages, including lower energy requirements, reduced secondary pollution, and superior ecological compatibility. This review synthesizes current knowledge on RRB’s biological characteristics, molecular resistance mechanisms, and applications in radioactive wastewater treatment. Moreover, potential applications in non-radioactive wastewater treatment—such as selective removal of heavy metals, degradation of refractory organics, and mitigation of antibiotic resistance—are discussed. Evidence from existing studies indicates that RRB share fundamental adaptive traits, including extraordinary radiotolerance, unique morphological modifications, and cross-tolerance to multiple stressors, which are underpinned by specialized DNA repair systems, potent antioxidant defenses, and radiation-responsive regulatory networks. These mechanisms collectively confer the ability to withstand and mitigate radiation-induced damage. Future research should responsibly prioritize the genetic engineering of RRB and its integration with complementary technologies, such as microbial fuel cells, to achieve synergistic pollutant removal and energy recovery. This synthesis provides a theoretical basis and technical reference for advancing RRB-enabled bioremediation toward sustainable wastewater management. Full article

Environmental pollutants such as heavy metals, endocrine-disrupting chemicals, microplastics, and airborne particulates are increasingly recognized for their potential to influence immune function through epigenetic mechanisms. This review examines conserved pollutant-associated pathways at interfaces of immunity and epigenetics, with particular attention to Toll-like receptor–NF-κB signalling, NLRP3 inflammasome activity, and reactive oxygen species-driven cascades. Evidence from cellular, animal, and epidemiological studies indicates that these pathways may converge on chromatin regulators such as DNA methyltransferases, histone deacetylases, and EZH2, leading to DNA methylation shifts, histone modifications, and altered chromatin accessibility. Pollutants are also reported to modulate non-coding RNAs, including miR-21, miR-155, and several lncRNAs, which can act as intermediaries between cytokine signalling and epigenetic remodelling. Findings from transgenerational models suggest that pollutant-linked immune–epigenetic alterations might persist across generations, raising the possibility of long-term consequences for immune and neurodevelopmental health. Comparative analyses further indicate convergence across diverse pollutant classes, pointing to a shared mechanistic axis of immune–epigenetic disruption. Overall, these insights suggest that pollutant-induced immune–epigenetic signatures may contribute to inflammation, altered immune responses, and heritable disease risks, and their clarification could inform biomarker discovery and future precision approaches in immunotoxicology. Full article

Cervical cancer remains a significant public health challenge, disproportionately affecting women in low- and middle-income countries (LMICs). Persistent infection with high-risk types of human papillomavirus (HPV), particularly HPV16 and HPV18, is the central cause of cervical carcinogenesis, driven by the viral oncoproteins E6 and E7, which disrupt the host tumor suppressors p53 and retinoblastoma protein (pRb). Advances in molecular understanding have catalyzed effective primary and secondary prevention strategies. Prophylactic HPV vaccination, especially the nonavalent formulation, has demonstrated high efficacy in reducing HPV infections and cervical precancer. Concurrently, HPV deoxyribonucleic acid (DNA) testing, self-sampling, and screen-and-treat protocols are transforming screening paradigms, particularly in resource-limited settings. However, global disparities in vaccine access, screening coverage, and health infrastructure persist, impeding progress toward the World Health Organization’s (WHO) 90–70–90 elimination targets. By synthesizing recent advances in virology, prevention strategies, and implementation innovations, such as therapeutic vaccines, artificial-intelligence (AI)-driven diagnostics, and mobile health solutions, this review sheds light on their potential to narrow these equity gaps. Full article

Myocardial infarction-induced cardiovascular diseases remain a leading cause of mortality worldwide. Excessive post-infarct fibrosis contributes to adverse cardiac remodeling and the progression to heart failure. In vivo reprogramming strategies offer a promising avenue for heart regeneration by directly converting resident fibroblasts into cardiomyocytes through enforced expression of cardiogenic genes. This approach circumvents the need for invasive biopsies, cell expansion, induction of pluripotency, or autologous transplantation. Despite these advantages, key challenges persist, including low reprogramming efficiency and limited cellular targeting specificity. A critical factor for effective anti-fibrotic therapy is the precise and efficient delivery of reprogramming effectors specifically to fibrotic fibroblasts, while minimizing off-target effects on non-fibroblast cardiac cells and fibroblasts in non-cardiac tissues. In this review, we discuss the cellular and molecular mechanisms underlying in vivo cardiac reprogramming, with a focus on fibroblast heterogeneity, key transcriptional drivers, and relevant intercellular interactions. We also examine current advances in fibroblast-specific delivery systems employing both viral and non-viral vectors for the administration of lineage-reprogramming factors such as cDNA overexpressions or microRNAs. Finally, we underscore innovative strategies that hold promise for enhancing the precision and efficacy of cellular reprogramming, ultimately fostering translational development and paving the way for rigorous preclinical assessment. Full article

The discovery of Asgard archaea has reshaped our understanding of eukaryotic origins, supporting a two-domain tree of life in which eukaryotes emerged from Archaea. Building on this revised framework, we propose the Pre-prokaryotic Organismal Lifeforms Existing Today (POLET) hypothesis, which suggests that relic pre-prokaryotic life forms—termed POLETicians—may persist in deep, anoxic, energy-limited environments. These organisms could represent a living bridge to the RNA world and other origin-of-life models, utilizing racemic oligoribonucleotides and peptides, non-enzymatic catalysis, and mineral-assisted compartmentalization. POLETicians might instead rely on radical-based redox chemistry or radiolysis for energy and maintenance. These biomolecules may be racemic or noncanonical, eluding conventional detection. New detection methods are required to determine such life. We propose generalized nanopore sequencing of any linear polymer—including mirror RNAs, mirror DNAs, or any novel genetic material—as a potential strategy to overcome chirality bias in modern sequencing technologies. These approaches, combined with chiral mass spectrometry and stereoisomer-resolved analytics, may enable the detection of molecular signatures from non-phylogenetic primitive lineages. POLETicians challenge the assumption that all life must follow familiar biochemical constraints and offer a compelling extension to our search for both ancient and extant forms of life hidden within Earth’s most extreme environments. Full article

Background: Hormone receptor-positive (HR+), HER2-negative breast cancer accounts for the majority of breast cancer diagnoses. While outcomes have improved with neoadjuvant and adjuvant therapies, the risk of late recurrence persists, and there remains a critical need for reliable biomarkers to guide prognosis and post-treatment surveillance. Circulating tumor DNA (ctDNA), detectable via liquid biopsy, has emerged as a promising tool for monitoring minimal residual disease and predicting survival outcomes. This systematic review evaluates the association between ctDNA detection during neoadjuvant or adjuvant treatment and survival outcomes in early-stage HR+/HER2− breast cancer. Methods: This systematic review was conducted in accordance with PRISMA guidelines. A comprehensive literature search of Ovid MEDLINE and Embase was conducted to identify studies published through 3 May 2024 that evaluated ctDNA as a prognostic biomarker in stage I–III HR+/HER2− breast cancer. We included studies reporting recurrence-free survival, invasive disease-free survival, or overall survival and excluded non-original studies, conference abstracts, and non-English articles. Data extraction and qualitative synthesis were performed, and the risk of bias was qualitatively assessed across studies. No review protocol was registered. Results: Eleven studies comprising 1644 patients met the inclusion criteria. In the neoadjuvant setting, ctDNA positivity prior to treatment initiation was associated with inferior survival outcomes. In the adjuvant setting, detection of ctDNA during or after treatment was consistently linked to poorer recurrence-free and invasive disease-free survival. Across studies, ctDNA detection was a significant negative prognostic marker. Conclusions: This systematic review supports the prognostic value of ctDNA in HR+/HER2− early-stage breast cancer. Limitations include small sample sizes, observational study designs, and heterogeneity in ctDNA assays. Standardization of ctDNA testing methods and further prospective trials are needed to validate its clinical utility and explore its potential role in guiding therapeutic interventions. Full article

Equine semen preservation is fundamental to modern equine reproduction, supporting breeding programs, genetic conservation, and industry sustainability. However, significant challenges persist, including temperature sensitivity, oxidative stress, bacterial contamination, individual variability, and lack of standardized preservation protocols. These factors contribute to reduced sperm viability and fertility following cryopreservation. This review examines critical obstacles in equine semen preservation, focusing on cryopreservation sensitivity, molecular damage mechanisms, economic constraints, and seasonal quality variations. We analyze the molecular and structural alterations (e.g., oxidative stress, membrane damage, and DNA fragmentation) and their impact on cryopreservation success. The review evaluates evidence-based enhancement strategies, including nutritional supplementation and genetic approaches, for improving semen quality. Nutritional interventions that utilize antioxidants, polyunsaturated fatty acids (PUFAs), and nutraceuticals have demonstrated promising results in enhancing sperm motility, preserving membrane integrity, and improving overall semen quality. Additionally, we discuss key candidate genes associated with equine semen-quality traits, including sperm motility, viability, and cryotolerance. The integration of nutritional supplementation and genetic selection strategies presents viable pathways for optimizing equine semen preservation techniques. These combined approaches offer potential solutions for overcoming current limitations, ultimately supporting sustainable breeding programs and advancing genetic conservation efforts in the equine industry. Full article

Quaternary ammonium compounds (QACs) are a class of chemicals used for their antimicrobial, surfactant, and antistatic properties. QACs are present in many consumer products, and people are regularly exposed to them. We have previously shown reproductive toxicity in mice exposed to the disinfectants alkyl dimethyl benzyl ammonium chloride (ADBAC) and dodecyl dimethyl ammonium chloride (DDAC). To assess the long-term reproductive impacts, a generational reproductive study was conducted. Sperm parameters were determined by CASA and epigenetic enzyme mRNA expression was determined by pathway-focused RT-PCR. Mice ambiently exposed to ADBAC+DDAC exhibited decreases in reproductive indices that persisted through the F1 generation. Male mice (F0) dosed with 120 mg/kg/day of ADBAC+DDAC exhibited decreased sperm concentration and motility that persisted through the F1 generation. Changes in the mRNA expression of chromatin-modifying enzymes in the testes were seen. Two histone acetyltransferases (Hat1 and Kat2b) were upregulated, and one lysine-specific demethylase (Kdm6b) was downregulated in the F0 generation. The DNA methyltransferase Dnmt1 was downregulated in F1 males. These changes in chromatin-modifying enzymes are known to decrease fertility and could be a mechanism for ADBAC+DDAC reproductive toxicity. In all experiments, the F2 generation was similar to the controls, showing multi-generational but not trans-generational epigenetic inheritance. Full article

Electrochemical biosensors have emerged as a promising tool for the early detection of diseases in oilseed crops such as rapeseed, soybean, and peanut. These biosensors offer high sensitivity, portability, and cost-effectiveness. Timely diagnosis is critical, as many pathogens exhibit latent infection phases or produce invisible metabolic toxins, leading to substantial yield losses before visible symptoms occur. This review summarises recent advances in the field of nanomaterial-assisted electrochemical sensing for oilseed crop diseases, with a particular focus on sensor mechanisms, interface engineering, and biomolecular recognition strategies. The following innovations are highlighted: nanostructured electrodes, aptamer- and antibody-based probes, and signal amplification techniques. These innovations have enabled the detection of pathogen DNA, enzymes, and toxins at ultra-low concentrations. Notwithstanding these achievements, challenges persist, including signal interference from plant matrices, limitations in device miniaturization, and the absence of standardized detection protocols. Future research should explore the potential of AI-assisted data interpretation, the use of biodegradable sensor materials, and the integration of these technologies with agricultural IoT networks. The aim of this integration is to enable real-time, field-deployable disease surveillance. The integration of laboratory innovations with field applications has been demonstrated to have significant potential in supporting sustainable agriculture and strengthening food security through intelligent crop health monitoring. Full article

Patients with First-Episode Psychosis (FEP) exhibit variable responses to antipsychotic treatment. Emerging evidence suggests that disease-related dysbiosis of gut and oropharyngeal microbiota may lead to the abnormal translocation of microorganisms via the bloodstream. This study aims to explore the blood microbiome to identify candidate biomarkers associated with treatment outcomes in FEP. To address this, blood samples were collected from twenty drug-naïve individuals with FEP, both before and after four weeks of antipsychotic medication. DNA extracted from these samples underwent 16S rRNA gene sequencing and comprehensive bioinformatics analysis. Clinical assessments were based on the Positive and Negative Syndrome Scale and standard remission criteria. Peripheral cytokines (IL1β, TNF-α, IL10) were quantified by immunoassays. Baseline comparisons showed a significantly greater microbiome alpha diversity in remitters, along with differential prevalence in five taxa and 217 metabolic pathways. Post-treatment assessments uncovered a significantly distinct impact of antipsychotics on blood bacterial composition between remission groups, while initial differences on metabolic profiles persisted. Additionally, strong correlations were observed, linking specific taxa abundances to cytokine levels. Conclusively, this pilot study suggests that blood microbiome profiling could provide novel biomarkers for predicting therapeutic response in early psychosis, paving the way for precision medicine interventions. Full article

Genome-wide paternal uniparental isodisomy mosaicism (GWpUPIDM) is an extremely rare condition characterized by varying proportions of an androgenetic cell line across different tissues. It is primarily associated with severe congenital hyperinsulinism (CHI), Beckwith–Wiedemann syndrome (BWS) stigmata, a high risk (69–79%) of developing neoplasia and, in some cases, additional manifestations of multilocus paternal imprinting disorders (MPIDs). We herein report the first Mexican/Latin American female patient GWpUPIDM presenting with non-syndromic CHI requiring subtotal pancreatectomy and persistent but unexplained asymptomatic diffuse hepatopathy. When she was 8.5 years old, whole-exome sequencing (WES) in blood revealed an unexpectedly high (~92%) proportion of regions of homozygosity. DNA profiling confirmed a single haploid set of paternal chromosomes in both biparental and androgenetic cell lines, with varying proportions of the androgenetic lineage in leukocytes (84%), resected pancreas (74%), buccal cells (47%), and hair follicles (0.7%). Additional WES trio analysis using gDNA from the patient’s buccal cells and blood samples from both parents revealed an allelic frequency of ~75% for the paternally inherited variant NM_000158.4(GBE1):c.555+1G>T [ClinVar:632422; dbSNP:rs759707498]. At age 8.5, the patient exhibited no clinical features of BWS, MPIDs, or neoplasia. However, she presented persistent hepatic abnormalities that warrant further investigation to rule out an unmasked glycogen storage disease type IV (OMIM#232500). Our findings emphasize the critical need for early diagnosis of GWpUPIDM using SNP-based microarray or WES with further confirmation through DNA profiling in patients presenting with CHI, placental mesenchymal dysplasia, BWS stigmata, or other MPID-related conditions, including neoplasia, to facilitate timely cancer surveillance and management. Full article

Background: Robust evidence supports the role of tetrahydrobiopterin (BH4) metabolism in sustaining inflammation; however, the mechanisms underlying the persistent upregulation of the BH4 pathway remain incompletely understood. This study investigated the epigenetic regulation of BH4 metabolism following a single injection of lipopolysaccharide (LPS) in the mouse hippocampus. Methods: Male C57BL/6J mice received either saline or LPS (0.33 mg/kg, i.p.) and were sacrificed at 4 h or 24 h post injection. Behavioral assessments and analyses of hippocampal neurotransmitter metabolism, DNA methylation profile, oxidative stress, and inflammasome activation were performed. Neopterin levels, a marker of immune system activation, were measured in both the plasma and hippocampus. Results: LPS-treated mice exhibited sickness behavior, including reduced locomotor and exploratory activity at both 4 and 24 h. While exploratory behavior showed partial recovery by 24 h, locomotor activity remained impaired. Neopterin levels increased in both the plasma and hippocampus following LPS administration but returned to baseline in the hippocampus by 24 h. Despite the normalization of neopterin, a persistent pro-inflammatory state in the hippocampus was evident at 24 h, as shown by increased expression of Ikbkb and components of the NLRP3 inflammasome, along with elevated oxidative stress markers. Upregulation of Nrf-2 and Hmox1 suggested activation of a protective antioxidant response. Dopaminergic metabolism was disrupted, indicating impaired BH4-dependent dopamine turnover. Epigenetic analysis revealed increased expression of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b) and Tet2, along with reduced expression of Tet1 and Tet3. Promoter hypomethylation of Gch1 and Ptps was observed, correlating with increased hippocampal expression and potentially elevated BH4 levels. Conclusions: Together, these findings show that a single LPS challenge was sufficient to induce the activation of the BH4 synthesis pathway during the late acute inflammatory phase, both systemically and in the hippocampus, potentially driven by epigenetic modifications such as promoter hypomethylation. This may contribute to the perpetuation of neuroinflammation. Full article

COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these pathophysiological manifestations and the predictors of this multi-organ pathology like the persistence of the virus, altered endothelial function, unrepaired tissue damage, immune dysregulation, and gut dysbiosis. We also discuss the similarities between long COVID and vaccine side effects together with possible common immuno-inflammatory pathways. Since the spike protein is present in SARS-CoV-2 (and its variants) but also produced by the COVID vaccines, its toxicity may also apply to all mRNA or adenoviral DNA vaccines as they are based on the production of a very similar spike protein to the virus. After COVID infection or vaccination, the spike protein can last for months in the body and may interact with ACE2 receptors and mannan-binding lectin (MBL)/mannan-binding lectin serine protease 2 (MASP-2), which are present almost everywhere in the organism. As a result, the spike protein may be able to trigger inflammation in a lot of organs and systems similar to COVID infection. We suggest that three immuno-inflammatory pathways are particularly key and responsible for long COVID and COVID vaccine side effects, as it has been shown for COVID, which may explain in large part their strong similarities: the renin–angiotensin–aldosterone system (RAAS), the kininogen–kinin–kallikrein system (KKS), and the lectin complement pathway. We propose that therapeutic studies should focus on these pathways to propose better cures for both long COVID as well as for COVID vaccine side effects. Full article

Background/Objectives: Inteins are mobile genetic elements invading highly conserved genes across all domains of life and viruses. Five active intein insertion sites (MCM-a through e) had previously been identified and studied in the archaeal replicative helicase minichromosome maintenance (MCM) subunit gene mcm, making MCM an ideal system for dissecting the dynamics of multi-intein genes. However, work in this system thus far has been limited to particular archaeal groups. To better understand the dynamics and diversity of these inteins, MCM homologs spanning all archaeal groups were extracted from NCBI’s non-redundant protein sequence database, and the distribution and structural architectures of their inteins were characterized. Methods: The amino acid sequences of 4243 archaeal MCM homologs were retrieved from NCBI’s non-redundant protein sequence database. These sequences were systematically assessed for their intein content through within-group multiple sequence alignments. To characterize the inteins present at each site, extensive intein structure predictions and comparisons were performed. Phylogenetic analyses were used to investigate intein relatedness between and within sites, as well as the distribution of different MCM inteins in geographically overlapping populations of archaea. Results: In total, 11 active MCM intein insertion sites were identified, expanding on the previously known five. The insertion sites have varied invasion activity levels across archaeal groups, with Nanobdellati (DPANN) being the only group with all 11 sites active. In all but two (Methanonatronarchaeia and Hadarchaeota) of the archaeal groups studied where inteins were present, at least one MCM homolog was invaded by more than one intein. With respect to intein structure, within-intein insertions bearing semblance to DNA-binding domains were identified, with varied presence between inteins. Additionally, a study of archaeal MCM sequences of samples collected from the Atacama Desert in June 2013 revealed high MCM intein diversity levels. Conclusions: We identified six new active intein insertion sites in archaeal MCM, more than doubling the five previously known sites. All eleven intein insertion sites were either close to the ATP binding site, or the lined the channel through which the single-stranded DNA is pulled during the catalytic cycle of the helicase. Many of the analyzed inteins contained insertions bearing similarity to DNA-binding helix-turn-helix domains suggesting potential involvement in the intein homing process. Additionally, the high levels of MCM intein diversity observed in archaea from the Atacama Desert provide novel and strong support for a co-existence model of intein persistence. Full article