Silver nanoparticles: applications and toxic risks to human health and environment

Se estima que de todos los nanomateriales utilizados en productos para el consumo, las nanopartículas de plata (AgNPs) son las que tienen un mayor grado de comercialización. Se utilizan en electrónica, ropa, pinturas, cosméticos, bactericidas, biofungicidas, aplicaciones biomédicas, en la industria médico-farmaceútica y alimentaria. Por ello, se hace tremendamente necesario que los productos fabricados con nanopartículas así como sus aplicaciones sean seguros tanto para la salud de las personas como del medio ambiente. Algunos estudios han mostrado que la toxicidad intrínseca de las AgNPs depende de una serie de factores como son el tamaño, la forma, el área superficial, la carga superficial, la solubilidad y el estado de aglomeración. Asimismo, numerosas investigaciones in vitro indican que las AgNPs son tóxicas para las células de mamífero. Además, consecuencias inflamatorias, oxidativas y genotóxicas están asociadas con la exposición de AgNPs. Este artículo muestra una visión global de las principales aplicaciones de las AgNPs, sus vías de exposición, sus efectos tóxicos y los mecanismos de toxicidad implicados.It is estimated that of all the nanomaterials used in consumer products, silver nanoparticles (AgNPs) currently have the highest degree of commercialization. They are used in electronics, clothing, paints, cosmetic, bactericides, bio-fungicides, biomedical applications, in the medical-pharmaceutical industry and food industry. Therefore, it is extremely necessary that products made with nanoparticles as well as their applications are safe for the health and the environment. Some studies have shown that the intrinsic toxicity of AgNPs depend on a range of factors such as, size, shape, surface area, surface charge, solubility and state of agglomeration. In addition, a number of in vitro studies indicate that AgNPs are toxic to mammalian cells. Furthermore, inflammatory, oxidative and genotoxic consequences are associated with AgNPs exposure. This paper shows a global view of the main applications of AgNPs, their routes of exposure, toxic effects and toxicity mechanisms involved

N-nitrosopiperidina y N-nitrosodibutilamina (II): relevancia en la carcinógenesis química y genotoxicidad

La N-nitrosopiperidina (NPIP) y la N-nitrosodibutilamina (NDBA) han sido clasificadas como posibles carcinógenos en humanos. La NPIP causa tumores en esófago, y también en cavidad nasal, hígado y estómago, mientras que la NDBA es carcinógeno de vejiga urinaria. Ambas N-nitrosaminas son consideradas carcinógenos genotóxicos indirectos puesto que necesitan una bioactivación para generar metabolitos que reaccionen con el DNA. La principal lesión al DNA inducida por las N-nitrosaminas es el daño alquilativo. En el caso de la NDBA, la posición de alquilación es en el O6 de la guanina, formando la O6 butilguanina y la O6-4-hidroxibutilguanina. Sin embargo, esta N-nitrosamina alquila preferentemente proteínas. Por otra parte, la bioactivación de la NPIP genera metabolitos que reaccionan con el N2 de la guanina in vitro, aunque se desconocen sus efectos in vivo. Además, durante la activación metabólica pueden también producirse especies reactivas del oxígeno (EROs) y del nitrógeno (ERNs). Las lesiones oxidativas y nitrativas más comunes son la 8- hidroxideoxiguanosina (8 OHdG) y la 8-nitroguanina, respectivamente, que producen mutaciones y conducen a la carcinogénesis.N-nitrosopiperidine (NPIP) and N-nitrosodibutylamine (NDBA) have been classified as possibly carcinogenic to humans. NPIP causes tumours in oesophagus, and also in nasal cavity, liver and stomach, whereas NDBA is a bladder carcinogen. Both N-nitrosamines are considered indirect genotoxic carcinogens since they need a bioactivation to generate metabolites that react with DNA. The main DNA lesion induced by N nitrosamines is the alkylative damage. In the case of NDBA, the alkylation position is in O6 of guanine, forming O6 butylguanine and O6-4-hydroxybutylguanine. However, this N-nitrosamine alkylates proteins preferably. On the other hand, NPIP bioactivation generates metabolites that react with N2 of guanine in vitro, although its in vivo effects are unknown. Moreover, during metabolic activation reactive oxygen species (ROS) and nitrogen species (RNS) can be also produced. The most common oxidative and nitrative lesions are 8-hydroxydeoxyguanosine (8-OhdG) and 8-nitroguanine, respectively, that produce mutations and lead to carcinogenesis

N-nitrosopiperidina y N-nitrosodibutilamina (I): formación, exposición humana y metabolismo

Los vegetales, el agua de bebida y los productos cárnicos son las principales fuentes de exposición de nitratos en humanos. La toxicidad de estos compuestos es resultado de su conversión en nitritos que actúan como agentes nitrosantes en la formación de las Nnitrosaminas. Las N-nitrosaminas son uno de los grupos de agentes carcinogénicos más estudiados y existe una gran preocupación debido a su presencia en nuestra vida diaria. Sin embargo, son muy escasos los estudios realizados con dos N-nitrosaminas, la Nnitrosopiperidina (NPIP) y la N-nitrosodibutilamina (NDBA). La NPIP se encuentra en productos cárnicos que incluyan especias en la formulación de sus mezclas y la NDBA en productos cárnicos envasados en goma y en chupetes y tetinas para biberones. Además, la NPIP y la NDBA son compuestos genotóxicos indirectos que necesitan una activación metabólica para dañar el DNA y ejercer su efecto carcinogénico. Este proceso es llevado a cabo por el citocromo P450, en concreto, por las isoformas enzimáticas CYP 2A6 y el CYP 1A1, respectivamente.Vegetables, drinking water and meat products are the main sources of exposure to nitrates in humans. The toxicity of these compounds is usually the result of the conversion of nitrates into nitrites, which act as nitrosating agents in the N-nitrosamine formation. N-nitrosamines are one of the most studied carcinogenic group and great concern exists due to its presence in our daily life. However, the performed studies with two N-nitrosamines, N-nitrosopiperidine (NPIP) and N-nitrosodibutylamine (NDBA), are very limited. NPIP is found in meat products with spices in their formulation and NDBA in meat products packed in rubber nettings and in pacifiers and nipples. Moreover, NPIP and NDBA are indirect genotoxic compounds that need a metabolic activation to damage DNA and exert their carcinogenic effect. This process is carried out by cytochrome P450, in particular, by enzymatic isoforms CYP 2A6 y el CYP 1A1, respectively

Can online travel agencies contribute to the recovery of the tourism activity after a health crisis?

Purpose Online travel agencies (OTAs) have an important role to play in reactivating tourism activity following a health crisis by providing information about the health conditions of tourist destinations. Once developed, it is necessary to analyze the effectiveness of the information provided and ascertain whether the provision of such information effects the understanding of the value of using OTAs and, in turn, the intention to do so. Design/methodology/approach This paper, based on an empirical case study conducted during the COVID-19 pandemic, examines whether following a health crisis, the quality of information provided by OTAs on the health conditions of tourist destinations and the perceived value of their offer generate a greater OTA services reuse intention, and signals, therefore, a return to travel. Findings The results show the quality of the information positively influences the perceived value, but not the OTA services reuse intention. Rather, the perceived value positively influences the OTA services reuse intention. Practical implications Overall, it can be suggested that providing quality health information for a destination is a necessary strategy because it contributes to increasing the perceived value of OTAs. To incentivize the intention for repeated use of OTA services, it is necessary to consider the perceived value that influences the intention to make repeat OTA reservations. Originality/value This research offers a novel perspective about the OTAs’ contribution to the recovery of the activity of the tourism industry after a health crisis. This contributes to achieving a more resilient sector in the face of future health crises

Ipsilateral vagotomy to unilaterally ovariectomized pre-pubertal rats modifies compensatory ovarian responses

The present study evaluates the participation of the vagus nerve in pre-pubertal rats with unilateral ovariectomy on puberty onset, and on progesterone, testosterone and estradiol serum levels, and the compensatory responses of the ovary. Unilateral vagotomy did not modify the onset of puberty in unilaterally ovariectomized rats. Ovulation rates of animals with the left vagus nerve sectioned and the left ovary in-situ was lower than in rats with only unilateral ovariectomy. Sectioning the left vagus to 32-day old rats with the left ovary in-situ resulted in lower compensatory ovarian hypertrophy than in rats with right unilateral ovariectomy. Twenty-eight or 32-day old animals with sectioning of the right vagus nerve and the right ovary in situ showed higher compensatory ovulation. Twenty-eight -day old rats with the right ovary in situ had higher progesterone and testosterone levels than animals of the same age with the left ovary in-situ. Compared to animals with the right ovary in situ, animals treated at 32-days of age, sectioning the ipsi-lateral vagus nerve resulted in higher progesterone levels. Higher progesterone levels were observed in 28- and 32 days old rats with the left ovary in situ and left vagus nerve sectioned. Thirty-two day old animals with the right ovary in situ and right vagus nerve sectioned had higher progesterone levels than rats of the same age with the left ovary in situ and left vagus nerve sectioned. Left vagotomy to 28-day old rats with the left ovary in situ resulted in higher testosterone levels, a reverse response to that observed in animals with sectioning of the right vagus and the right ovary in situ. Thirty-two day old rats with the left ovary in situ and left vagus nerve sectioned showed lower testosterone levels than animals without vagotomy and with the left ovary in situ

Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors

Hypertension, diabetes and obesity are cardiovascular risk factors closely associated to the development of renal and cardiovascular target organ damage. VAV2 and VAV3, members of the VAV family proto-oncogenes, are guanosine nucleotide exchange factors for the Rho and Rac GTPase family, which is related with cardiovascular homeostasis. We have analyzed the relationship between the presence of VAV2 rs602990 and VAV3 rs7528153 polymorphisms with cardiovascular risk factors and target organ damage (heart, vessels and kidney) in 411 subjects. Our results show that being carrier of the T allele in VAV2 rs602990 polymorphism is associated with an increased risk of obesity, reduced levels of ankle-brachial index and diastolic blood pressure and reduced retinal artery caliber. In addition, being carrier of T allele is associated with increased risk of target organ damage in males. On the other hand, being carrier of the T allele in VAV3 rs7528153 polymorphism is associated with a decreased susceptibility of developing a pathologic state composed by the presence of hypertension, diabetes, obesity or cardiovascular damage, and with an increased risk of developing altered basal glycaemia. This is the first report showing an association between VAV2 and VAV3 polymorphisms with cardiovascular risk factors and target organ damage

Assessing the causal role of epigenetic clocks in the development of multiple cancers: a Mendelian randomization study

Background: Epigenetic clocks have been associated with cancer risk in several observational studies. Nevertheless, it is unclear whether they play a causal role in cancer risk or if they act as a non-causal biomarker. Methods: We conducted a two-sample Mendelian randomization (MR) study to examine the genetically predicted effects of epigenetic age acceleration as measured by HannumAge (nine single-nucleotide polymorphisms (SNPs)), Horvath Intrinsic Age (24 SNPs), PhenoAge (11 SNPs), and GrimAge (4 SNPs) on multiple cancers (i.e. breast, prostate, colorectal, ovarian and lung cancer). We obtained genome-wide association data for biological ageing from a meta-analysis (N = 34,710), and for cancer from the UK Biobank (N cases = 2671-13,879; N controls = 173,493-372,016), FinnGen (N cases = 719-8401; N controls = 74,685-174,006) and several international cancer genetic consortia (N cases = 11,348-122,977; N controls = 15,861-105,974). Main analyses were performed using multiplicative random effects inverse variance weighted (IVW) MR. Individual study estimates were pooled using fixed effect meta-analysis. Sensitivity analyses included MR-Egger, weighted median, weighted mode and Causal Analysis using Summary Effect Estimates (CAUSE) methods, which are robust to some of the assumptions of the IVW approach. Results: Meta-analysed IVW MR findings suggested that higher GrimAge acceleration increased the risk of colorectal cancer (OR = 1.12 per year increase in GrimAge acceleration, 95% CI 1.04-1.20, p = 0.002). The direction of the genetically predicted effects was consistent across main and sensitivity MR analyses. Among subtypes, the genetically predicted effect of GrimAge acceleration was greater for colon cancer (IVW OR = 1.15, 95% CI 1.09-1.21, p = 0.006), than rectal cancer (IVW OR = 1.05, 95% CI 0.97-1.13, p = 0.24). Results were less consistent for associations between other epigenetic clocks and cancers. Conclusions: GrimAge acceleration may increase the risk of colorectal cancer. Findings for other clocks and cancers were inconsistent. Further work is required to investigate the potential mechanisms underlying the results. Funding: FMB was supported by a Wellcome Trust PhD studentship in Molecular, Genetic and Lifecourse Epidemiology (224982/Z/22/Z which is part of grant 218495/Z/19/Z). KKT was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme) and by the Hellenic Republic's Operational Programme 'Competitiveness, Entrepreneurship & Innovation' (OΠΣ 5047228). PH was supported by Cancer Research UK (C18281/A29019). RMM was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. GDS and CLR were supported by the Medical Research Council (MC_UU_00011/1 and MC_UU_00011/5, respectively) and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). REM was supported by an Alzheimer's Society project grant (AS-PG-19b-010) and NIH grant (U01 AG-18-018, PI: Steve Horvath). RCR is a de Pass Vice Chancellor's Research Fellow at the University of Bristol

Nature and Distribution of Stable Subsurface Oxygen in Copper Electrodes During Electrochemical CO₂ Reduction

Oxide-derived copper (OD-Cu) electrodes exhibit higher activity than pristine copper during the carbon dioxide reduction reaction (CO₂RR) and higher selectivity toward ethylene. The presence of residual subsurface oxygen in OD-Cu has been proposed to be responsible for such improvements, although its stability under the reductive CO₂RR conditions remains unclear. This work sheds light on the nature and stability of subsurface oxygen. Our spectroscopic results show that oxygen is primarily concentrated in an amorphous 1–2 nm thick layer within the Cu subsurface, confirming that subsurface oxygen is stable during CO₂RR for up to 1 h at −1.15 V vs RHE. Besides, it is associated with a high density of defects in the OD-Cu structure. We propose that both low coordination of the amorphous OD-Cu surface and the presence of subsurface oxygen that withdraws charge from the copper sp- and d-bands might selectively enhance the binding energy of CO

Adaptation and Preadaptation of Salmonella enterica to Bile

Bile possesses antibacterial activity because bile salts disrupt membranes, denature proteins, and damage DNA. This study describes mechanisms employed by the bacterium Salmonella enterica to survive bile. Sublethal concentrations of the bile salt sodium deoxycholate (DOC) adapt Salmonella to survive lethal concentrations of bile. Adaptation seems to be associated to multiple changes in gene expression, which include upregulation of the RpoS-dependent general stress response and other stress responses. The crucial role of the general stress response in adaptation to bile is supported by the observation that RpoS− mutants are bile-sensitive. While adaptation to bile involves a response by the bacterial population, individual cells can become bile-resistant without adaptation: plating of a non-adapted S. enterica culture on medium containing a lethal concentration of bile yields bile-resistant colonies at frequencies between 10−6 and 10−7 per cell and generation. Fluctuation analysis indicates that such colonies derive from bile-resistant cells present in the previous culture. A fraction of such isolates are stable, indicating that bile resistance can be acquired by mutation. Full genome sequencing of bile-resistant mutants shows that alteration of the lipopolysaccharide transport machinery is a frequent cause of mutational bile resistance. However, selection on lethal concentrations of bile also provides bile-resistant isolates that are not mutants. We propose that such isolates derive from rare cells whose physiological state permitted survival upon encountering bile. This view is supported by single cell analysis of gene expression using a microscope fluidic system: batch cultures of Salmonella contain cells that activate stress response genes in the absence of DOC. This phenomenon underscores the existence of phenotypic heterogeneity in clonal populations of bacteria and may illustrate the adaptive value of gene expression fluctuations