Search Results (57)

Although ART leads to viral suppression, people living with HIV (PLWH) still face an increased risk of comorbidities, such as cancer. The HIV-1 Tat protein may contribute to the promotion of chronic inflammation, oxidative stress, and genomic instability. While the presence of anti-Tat antibodies has been associated with slower disease progression, their potential role in modulating DNA damage remains unclear. Assess the effect of anti-Tat antibodies on cytotoxic and DNA damage in PLWH. A cross-sectional study was conducted in 178 PLWH. Serum anti-Tat IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Cytotoxicity and DNA damage were assessed via serum 8-hydroxy-2′-deoxyguanosine (8-OHdG) and nuclear anomalies (Micronucleus cytome assay) in 2000 buccal cells. Statistical significance was considered at p < 0.05. Anti-Tat antibodies were found in 24.2% of participants. Positive individuals had lower CD4+ T cell counts (p = 0.045) and higher levels of pyknosis (p = 0.0001). No differences in 8-OHdG were found, but 8-OHdG correlated positively with CD4+ counts (rho = 0.334, p = 0.006). Pyknosis negatively correlated with CD4+ counts (rho = −0.272, p = 0.027). Anti-Tat antibodies may not prevent DNA damage but could be related to cytotoxic effects in PLWH. Full article

Tuberculosis (TB) is a global public health issue requiring early and accurate diagnosis. The loop-mediated isothermal amplification (LAMP) assay is a promising alternative recommended by the WHO for the initial diagnosis of pulmonary TB, particularly in resource-limited settings. This study evaluated the sensitivity and specificity of a commercial LAMP assay for TB detection using 198 samples from different countries including Mexico. The LAMP assay results were compared to the results of standard tests: AFB smear microscopy, cell culture, and Xpert PCR. Across all samples, LAMP showed a sensitivity of 96.20% and a specificity of 84.61%. When compared specifically to “true positives” and “true negatives” (defined by the consistency across the standard tests), LAMP demonstrated 100% sensitivity and 92.30% specificity. For context, the sensitivity of AFB smear microscopy against the culture and Xpert tests was 79.04%. A significant finding was that the LAMP test detected a high percentage (92.5%) of samples found positive by the culture and Xpert tests but negative by the AFB smear, highlighting its ability to identify cases missed by traditional microscopy. This study concluded that the LAMP assay is a sensitive and specific tool for TB diagnosis with potential for rapid and accurate diagnosis, especially in resource-limited areas. Full article

In pathology laboratories, several volatile organic compounds (VOCs) are used, such as formaldehyde, ethanol, and xylene. These substances are recognized as genotoxic and cytotoxic, which is why their handling poses risks to human health. The buccal micronucleus (MN) cytome assay is a non-invasive, useful, and simple method to detect these effects in exposed individuals. The aim of the study was to evaluate the risk of genotoxicity and cytotoxicity of VOCs in pathology professionals of S. Miguel Island, Azores, Portugal. The study comprised two groups: exposed workers (n = 21) from the three laboratories of S. Miguel, and a reference group (n = 50), randomly chosen from other hospital services without known exposure to VOCs. The exfoliated buccal cells were auto-sampled by all the participants using a cytobrush. The samples were processed in ThinPrep^®, stained with modified Feulgen with Fast Green, and visualized for MN and other nuclear anomalies (ONAs), such as karyorrhexis, pyknotic, and karyolytic cells. Results showed that VOCs have a predictive significance for MN frequency, leading to the conclusion that their exposure is an increased risk factor for the health of these professionals, approximately four times greater than in the control group. Full article

This study evaluates DNA damage and multi-element exposure in populations from La Mojana, a region of North Colombia heavily impacted by artisanal and small-scale gold mining (ASGM). DNA damage markers from the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, including micronucleated binucleated cells (MNBN), nuclear buds (NBUDs) and nucleoplasmic bridges (NPB), were assessed in 71 exposed individuals and 37 unexposed participants. Exposed individuals had significantly higher MNBN frequencies (PR = 1.26, 95% CI: 1.02–1.57, p = 0.039). Principal Component Analysis (PCA) identified the “Soil-Derived Mining-Associated Elements” (PC1), including V, Fe, Al, Co, Ba, Se and Mn, as being strongly associated with high MNBN frequencies in the exposed population (PR = 10.45, 95% CI: 9.75–12.18, p < 0.001). GAMLSS modeling revealed non-linear effects of PC1, with greater increases in MNBN at higher concentrations, especially in exposed individuals. These results highlight the dual role of essential and toxic elements, with low concentrations being potentially protective but higher concentrations increasing genotoxicity. Women consistently exhibited higher MNBN frequencies than men, suggesting sex-specific susceptibilities. This study highlights the compounded risks of chronic metal exposure in mining-impacted regions and underscores the urgent need for targeted interventions to mitigate genotoxic risks in vulnerable populations. Full article

Propolis has been well known for centuries as a natural preventive and therapeutic agent. Its numerous health benefits are mainly attributed to its high content of phenolic compounds that have a remarkable antioxidant activity. Since phenolics may exert a dual nature (pro-oxidant and antioxidant) the aim of this study was to investigate the safety profile of the ethanolic extract of propolis and the related flavonoid galangin and their ability to protect lymphocytes from irinotecan-induced cyto/genotoxicity in vitro. Isolated human peripheral blood lymphocytes were exposed for 3 h to three concentrations of propolis extract and galangin corresponding to the average daily dose of 0.25 mL of extract [propolis in 70% ethanol (3:7, w/w)], as well as a five- and ten-fold higher concentration. Cyto- and genoprotective effects were tested using a cytokinesis-block micronucleus cytome assay. Treatment with propolis and galangin in the selected concentrations exerted high biocompatibility with lymphocytes and diminished the level of cytogenetic damage caused by irinotecan. Propolis at the same concentration offered a stronger protective effect than single galangin. Also, apoptosis was the prevailing mechanism of cell death in our experimental conditions. These preliminary results speak in favour of future investigations of propolis using other available cytogenetic methods and cell models. Full article

In Europe, there is a growing concern for animal welfare, encompassing both their rights and health. Consequently, identifying biomarkers that predict serious pathological conditions has become crucial in veterinary medicine. The Buccal Micronucleus Cytome (BMCyt) assay is a minimally invasive method that uses biomarkers to evaluate DNA damage and chromosomal instability, using exfoliated buccal cells. A rising frequency of anomalies, such as micronuclei formation, strongly indicates an elevated risk of cancer, neurodegenerative diseases, or accelerated aging, potentially originating from exposure to genotoxins and cytotoxins. This method has been validated in humans, but very little research has been conducted on animals. This work aims to provide a detailed description of an optimized method for collecting buccal exfoliated cells in dogs and to characterize a biomarker related to genomic damage using optical and fluorescent microscopy. Samples from dogs in breeding kennels, including pregnant animals, were tested for chromosomal instability. By following procedures similar to those used in humans, we were able to detect and count major nuclear abnormalities. The percentage of micronuclei was higher compared to other studies. Technical aspects, such as avoiding artifacts and ensuring prior training of the operator, must be taken into account. This work validated the BMCyt method for collecting and processing samples in dogs, potentially enhancing the understanding of micronuclei as biomarkers for pre-pathological states in canines. Full article

The prevalence of metabolic syndrome (MetS) worldwide is rapid and significant on a global scale. A 2022 meta-analysis of data from 28 million individuals revealed a global prevalence of 45.1%, with notably higher rates in the Eastern Mediterranean Region and the Americas, particularly in high-income countries. MetS is associated with impaired antioxidant defense mechanisms, resulting in the excessive generation of reactive oxygen and nitrogen species (RONS) and elevated levels of DNA damage. Unrepaired damage can lead to DNA base changes, chromosomal mutations, genomic loss and instability, and disrupted gene and protein expression. Such changes contribute to an increased risk of tumorigenesis, cancer progression, and mortality. The alkaline comet and micronucleus cytome assay are commonly used assays for DNA damage evaluation. The estimation of damage with those two techniques demonstrated the link between the increased risk of cancer and mortality. Incorporating these techniques in a set of biomarkers to assess the MetS severity holds promise; however, comprehensive literature reviews featuring large-scale studies integrating both assays remain scarce. This systematic review aims to integrate and critically evaluate the existing scientific literature regarding this topic. Full article

The increasing use of Cannabis sativa products for medicinal, dietary, and recreational purposes has raised concerns about mycotoxin contamination in cannabis and hemp. Mycotoxins persist in these products’ post-processing, posing health risks via multiple exposure routes. This study investigated cytotoxic and genotoxic interactions between cannabidiol (CBD) and the mycotoxin citrinin (CIT) using human cell models: SH-SY5Y, HepG2, HEK293, and peripheral blood lymphocytes. IC₅₀ values and membrane disruption were initially assessed, followed by an evaluation of genotoxicity in lymphocytes using the Comet Assay and Cytokinesis Blocked Micronucleus Cytome Assay. Obtained findings demonstrate that cell-type sensitivity varied across treatments, with combined CBD and CIT exposure exhibiting distinct interactions. Lactate dehydrogenase (LDH) release remained minimal, suggesting cytotoxicity did not stem from membrane disruption but likely involved intracellular pathways. In lymphocytes, CBD alone produced negligible cyto/genotoxic effects and weak antiproliferative responses, whereas CIT displayed clear toxic impacts. DNA damage indicates that CIT may induce genome instability through indirect mechanisms rather than direct DNA interaction, with evidence of potential aneuploidic effects from the CBMN Cyt Assay. Combined exposure led to a reduction in CIT-induced DNA and cytogenetic damage, suggesting CIT’s potential interference with the beneficial properties of CBD. These results provide a foundation for further toxicological assessments and highlight the necessity of standardized mycotoxin monitoring in cannabis-derived products. Full article

Even though anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) have improved survival, a high percentage of patients still do not respond to ICIs. Myeloid-derived suppressor cells (MDSCs) are circulating cells that express PD-L1 and can infiltrate and proliferate in the tumor microenvironment, inducing immunosuppression. By evaluating changes in PD-L1 expression of live peripheral blood MDSCs, we are able to define a new PD-L1 index, useful in predicting ICI escape in NSCLC patients before initiating anti-PD-1/PD-L1 immunotherapy. In this study, a cohort of 37 NSCLC patients was prospectively analyzed, obtaining independent PD-L1 indexes. In patients with a PD-L1 index > 5.88, progressive disease occurred in 58.33% of patients [median progression-free survival (PFS) = 5.73 months; 95%CI = 2.67–20.53], showing significant differences when compared with patients with a PD-L1 index ≤ 5.88, in whom 7.69% progressed and median PFS was not reached (NR); p-value = 0.0042. Overall survival (OS) was significantly worse in patients with a high vs. low PD-L1 index (41.67% vs. 76.92%; median OS = 18.03 months, 95%CI = 6.77–25.23 vs. NR, 95%CI = 1.87-NR; p-value = 0.035). The PD-L1 index can be applied to stratify NSCLC patients according to their probability of response to ICIs at baseline. In addition to quantifying tumoral expression, this index could be used to compare nonresponse to treatment. Full article

The characterization of wildland firefighters’ occupational exposure must consider different exposures, including those at the fire station. The present study aimed to characterize the occupational exposure of 172 Northern Portuguese wildland firefighters in fire stations during the pre-wildfire season of 2021. The biological impact of estimated inhaled doses of PM₁₀ and PM_2.5 (indoor/outdoor) was accessed through a buccal micronucleus cytome (BMCyt) assay in exfoliated buccal cells of a subgroup of 80 firefighters. No significant association was found between estimated inhaled doses of PM₁₀ and PM_2.5 (mean 1.73 ± 0.43 µg kg⁻¹ and 0.53 ± 0.21 µg kg⁻¹, respectively) and biological endpoints. However, increased frequencies of cell death parameters were found among subjects of the Permanent Intervention Teams (full-time firefighters). The intake of nutritional supplements was associated with a significant decrease in micronucleus frequencies (i.e., DNA damage or chromosome breakage). In addition, our findings showed a significantly increased frequency of cell death endpoints (i.e., nuclear fragmentation) with coffee consumption, while daily consumption of vegetables significantly decreased it (i.e., nuclear shrinkage). Our results provide data on the occupational exposure of wildland firefighters while working in fire stations during the pre-wildfire season, providing the essential baseline for further studies throughout the wildfire season. Full article

Sepsis is one of the most common causes of morbidity and mortality worldwide. Despite the remarkable advances in modern medicine throughout the last century, the mortality rates associated with sepsis have remained significantly elevated, both in high- and low-income countries. The main difficulty in the diagnosis and treatment of septic patients is the tremendous heterogeneity of this condition. The vast heterogeneity that characterizes sepsis ranges from the clinical presentation to the biological aspects of the disease. Evidence-based medicine approaches sepsis as a homogenous syndrome and does not consider the individual discrepancies between septic patients. This approach may contribute to the poor outcomes of septic patients. In recent years, personalized medicine has gained significant interest. This novel form of medicine underlines the importance of understanding the genetic, epigenetic, and molecular basis of a disease in order to provide a more tailored approach for the patient. The study of “omics”, such as cytomics, genomics, epigenomics, transcriptomics, proteomics, and metabolomics, provides a deeper comprehension of the complex interactions between the host, the disease, and the environment. The aim of this review is to summarize the potential role of a personalized approach in sepsis management, considering the interactions between various “omics”. Full article

Background: Cytogenotoxic damage caused by the consumption of legal and illegal drugs in drug abusers has been demonstrated, primarily due to alterations in their antioxidant capacity, cellular repair mechanisms, and increased production of free radicals. Folic acid shows antioxidant activity by acting as a reducing agent, neutralizing present free radicals, and reducing genomic damage. Methods: The intervention involved administering 15 mg of folic acid, divided into three doses per day, to a group of 44 drug abusers. The frequency of nuclear abnormalities (NAs) was determined; micronuclei (MNs), nuclear buds (NBUDs), binucleated cells (BNs), abnormally condensed chromatin (CC), karyorrhexis (KX), pyknotic nuclei (PNs), and karyolysis (KL) were determined at different pre-treatment (baseline) and post-treatment time points at 15 and 30 days. Additionally, a group of 44 healthy individuals was used as the control group. Results: We observed a statistically significant decrease in the frequency of NAs in the drug abuser group (28.45 ± 17.74 before supplementation vs. 11.18 ± 7.42 at 15 days and 9.11 ± 10.9 at 30 days of supplementation). Specifically, it decreased the frequency of NBUDs, BNs, CC, KX, and PNs (p < 0.05). Conclusion: Our study demonstrates a clear improvement in cytogenotoxic damage in drug abusers supplemented with folic acid. Full article

Aims/Objectives: The aim of this cross-sectional observational study was to investigate cytogenetic damage to the buccal mucosa in non-smokers and consumers of traditional combustible tobacco products and non-combustible alternatives. Methods: A total of 160 participants were divided into four groups according to the type of product used, including non-smokers, users of conventional combustible tobacco (cigarettes), heated tobacco, and electronic, tobacco-free vapor products (e-cigarettes). Buccal mucosa samples were analyzed using the micronucleus cytome assay to assess cytotoxic and genotoxic damage. Results: E-cigarette users showed significantly higher values for all tested parameters in the micronucleus test compared to non-smokers (p < 0.05). Similarly, users of tobacco heating products showed an increase in all parameters (p < 0.05), with the exception of the number of cells with micronuclei. Conventional cigarette smokers showed a notable increase in the number of binucleated cells and cells with karyorrhexis and karyolysis (p ≤ 0.05). When assessing the differences between users of traditional combustible tobacco products and non-combustible alternatives, these did not appear to be significant, except for e-cigarette users, who had significantly more cells with condensed chromatin (p ≤ 0.001), while users of tobacco heating products had more pyknotic cells (p ≤ 0.001). Conclusion: The results of this study underscore the heightened occurrence of cytotoxic and genotoxic damage in users of both conventional combustible tobacco products and non-combustible alternatives compared to non-smokers, emphasizing the detrimental impact of these products on the oral mucosa. Full article

Antibiotic resistance is now a first-order health problem, which makes the development of new families of antimicrobials imperative. These compounds should ideally be inexpensive, readily available, highly active, and non-toxic. Here, we present the results of our investigation regarding the antimicrobial activity of a series of natural and synthetic polyamines with different architectures (linear, tripodal, and macrocyclic) and their derivatives with the oxygen-containing aromatic functional groups 1,3-benzodioxol, ortho/para phenol, or 2,3-dihydrobenzofuran. The new compounds were prepared through an inexpensive process, and their activity was tested against selected strains of yeast, as well as Gram-positive and Gram-negative bacteria. In all cases, the conjugated derivatives showed antimicrobial activity higher than the unsubstituted polyamines. Several factors, such as the overall charge at physiological pH, lipophilicity, and the topology of the polyamine scaffold were relevant to their activity. The nature of the lipophilic moiety was also a determinant of human cell toxicity. The lead compounds were found to be bactericidal and fungistatic, and they were synergic with the commercial antifungals fluconazole, cycloheximide, and amphotericin B against the yeast strains tested. Full article

Flow cytometry is a single-cell based technology aimed to quantify the scattering of light and the emission of multiple fluorescence signals by individual cells, biological vesicles, or synthetic microscopical particles when examined one by one at high speed using lasers or other suitable illumination sources [...] Full article