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Cattle farming faces challenges linked to intensive exploitation and climate change, requiring the reinforcement of animal resilience in response to these dynamic environments. Currently, genetic selection is used to enhance resilience by identifying animals resistant to specific diseases; however, certain diseases, such as mastitis, pose difficulties in genetic prediction. This study introduced the utilization of enzymatic methyl sequencing (EM-seq) of the blood genomic DNA from twelve dairy cows to identify DNA methylation biomarkers, with the aim of predicting resilience and susceptibility to mastitis. The analysis uncovered significant differences between cows resilient and susceptible to mastitis, with 196,275 differentially methylated cytosines (DMCs) and 1,227 Differentially Methylated Regions (DMRs). Key genes associated with the immune response and morphological traits, including ENOPH1, MYL10 and KIR2DL5A, were identified by our analysis. Quantitative trait loci (QTL) were also highlighted and the body weight trait was the most targeted by DMCs and DMRs. Based on our results, the risk of developing mastitis can potentially be estimated with as few as fifty methylation biomarkers, paving the way for early animal selection. This research sets the stage for improved animal health management and economic yields within the framework of agricultural sustainability through early selection based on the epigenetic status of animals.
Assuntos
Metilação de DNA , Epigênese Genética , Mastite Bovina , Locos de Características Quantitativas , Animais , Bovinos/genética , Feminino , Mastite Bovina/genética , Predisposição Genética para Doença , Marcadores GenéticosRESUMO
Choline is a vital micronutrient that can be utilized in the formation of betaine and multiple phospholipids. In this study, we aimed to confirm, and expand on previous findings, how choline impacts embryos from the first 7 days of development to affect postnatal phenotype. Bos indicus embryos were cultured in a choline-free medium (termed vehicle) or medium supplemented with 1.8 mM choline Blastocyst-stage embryos were transferred into crossbred recipients. Once born, calves were evaluated at birth, 94 d, 178 d and at weaning (average age = 239 d). Following weaning, all calves were enrolled into a feed efficiency trial before being separated by sex, with males being slaughtered at approximately 580 d of age and females followed until their first pregnancy check. Results confirm that exposure of 1.8 mM choline chloride during the first 7 d of development alters postnatal characteristics of the resultant calves. Calves of both sexes from choline-treated embryos were consistently heavier through weaning and males had heavier testes at 3 mo of age. There were sex-dependent alterations in DNA methylation in whole blood caused by choline treatment. After weaning, feed efficiency was affected by an interaction with sex, with choline calves being more efficient for females and less efficient for males. Calves from choline-treated embryos were heavier, or tended to be heavier, than calves from vehicle embryos at all observations after weaning. Carcass weight was heavier for choline calves and the cross-sectional area of the Longissumus thoracis muscle was increased by choline. Few females became pregnant during the experiment although numerically more choline females were pregnant than vehicle females. Results confirm that exposure of the preimplantation embryo to 1.8 mM choline can alter phenotypes of the resultant calves through the first 19 months after birth.
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This work relates to the design and synthesis of a series of novel multi-target directed ligands (MTDLs), i.e., compounds 4a-l, via a convenient one-pot three-component Hantzsch reaction. This approach targeted calcium channel antagonism, antioxidant capacity, cathepsin S inhibition, and interference with Nrf2 transcriptional activation. Of these MTDLs, 4i emerged as a promising compound, demonstrating robust antioxidant activity, the ability to activate Nrf2-ARE pathways, as well as calcium channel blockade and cathepsin S inhibition. Dihydropyridine 4i represents the first example of an MTDL that combines these biological activities.
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Sperm small non-coding RNAs (sncRNAs), such as microRNAs (miRNAs) and tRNA-derived small RNAs (tsRNAs), have been found to have implications for male fertility and play a role in the intergenerational transmission of specific phenotypes by influencing the early embryo's physiological processes in various animal species. This study postulates that there exists a correlation between sperm small non-coding RNAs (sncRNAs) and bull fertility, which in turn can influence the fertility of offspring through the modulation of early embryo development. To investigate this hypothesis, we generated comparative libraries of sperm sncRNAs from sires exhibiting high (n = 3) versus low bull fertility (n = 3), as well as high (n = 3) versus low daughter fertility (n = 3), as determined by the industry-standard Bull fertility index and Daughter fertility index. In total, 12 tsRNAs carried by sperm (11 down-regulated and 1 up-regulated) were found to be associated with bull fertility, while 19 tsRNAs (11 down-regulated and 8 up-regulated) were found to be associated with daughter fertility (q < 0.05, Log2foldchange>±1.5, base mean > 50). Notably, tRX-Glu-NNN-3811 exhibited potential as a biomarker for predicting fertility in both male and female dairy cattle. Moreover, a total of six miRNAs sperm-borne (two up-regulated and four down-regulated) and 35 miRNAs (27 up-regulated and eight down-regulated) exhibited a significant correlation with both bull fertility and daughter fertility individually (p < 0.05, base mean > 50, log2foldchange>±1.5), two microRNAs, namely miR-2385-5p (down-regulated) and miR-98 (up-regulated), exhibit a significant association (p < 0.05, base mean > 50, log2foldchange>±1.5) with the fertility of both bulls and daughter. The targets of these two microRNAs were subsequently identified and integrated with the transcriptomic database of the embryonic cells at the two-cell stage, which is known to be indicative of embryonic competence. The KEGG analysis revealed a potential correlation between these targets and choline metabolism, a crucial factor in embryonic epigenetic programming. In summary, the findings of this study indicate that sperm-borne small non-coding RNAs (sncRNAs) hold promise as biomarkers for predicting and enhancing fertility in dairy cattle. Furthermore, it is plausible that these sncRNAs may exert their effects on daughter fertility by targeting genes in the early embryo.
Assuntos
MicroRNAs , Pequeno RNA não Traduzido , Masculino , Bovinos/genética , Animais , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Sêmen/metabolismo , Fertilidade/genética , Espermatozoides/fisiologia , Pequeno RNA não Traduzido/metabolismoRESUMO
The current decline in dairy cattle fertility has resulted in significant financial losses for dairy farmers. In the past, most efforts to improve dairy cattle fertility have been focused on either management or genetics, while epigenetics have received less attention. In this study, 12 bulls were selected from a provided 100 bull list and studied (High daughter fertility = 6, Low daughter fertility = 6) for Enzymatic methylation sequencing in the Illumina HiSeq platform according to the Canadian daughter fertility index (DFI), sires with high and low daughter fertility have average DFI of 92 and 112.6, respectively. And the bull list provided shows a mean DFI of 103.4. 252 CpGs with methylation differences greater than 20% (q < 0.01) were identified, as well as the top 10 promising DMRs with a 15% methylation difference (q < 1.1e-26). Interestingly, the DMCs and DMRs were found to be distributed more on the X chromosome than on the autosome, and they were covered by gene clusters linked to germ cell formation and development. In conclusion, these findings could enhance our ability to make informed decisions when deciding on superior bulls and advance our understanding of paternal epigenetic inheritance.
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Metilação de DNA , Sêmen , Bovinos/genética , Animais , Masculino , Núcleo Familiar , Canadá , Espermatozoides/metabolismo , Fertilidade/genéticaRESUMO
Early psychological factors, including childhood traumas and personality, play a crucial role in the emergence and persistence of painful symptoms and appears to be frequent in patients with nociplastic pain. Patient care involves validating the reality of their pain and identifying various facets of their suffering, taking into account their individual history and context. A multimodal therapeutic approach, within a bio-psycho-social model, emphasizing psychotherapeutic care, is recommended.
Les facteurs psychologiques précoces, notamment les traumatismes infantiles et la personnalité, jouent un rôle primordial dans l'émergence et la pérennisation des symptômes douloureux, et sont très fréquemment retrouvés chez les patients atteints de douleurs nociplastiques. La prise en charge des patients passe par la validation de la réalité de leur douleur et l'identification des diverses facettes de leur souffrance, en tenant compte de l'histoire et du contexte individuel. Une approche thérapeutique multimodale, dans un modèle de type biopsychosocial et privilégiant la prise en soins psychothérapeutique, est recommandée.
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Dor Crônica , Humanos , Dor Crônica/terapia , Ansiedade , Personalidade , Transtornos da PersonalidadeRESUMO
This study characterized variations in the methylation profile of mitochondrial DNA (mtDNA) during initial bovine embryo development and correlated the presence of methylation with mtDNA transcription. Bovine oocytes were obtained from abattoir ovaries and submitted to in vitro culture procedures. Oocytes and embryos were collected at various stages (immature oocyte, IM; mature oocyte, MII; zygote, ZY; 4-cells, 4C; 16-cells, 16C and blastocysts, BL). Total DNA (including mtDNA) was used for Whole Genome Enzymatic Methyl Sequencing and for quantification of mtDNA copy number. Extracted RNA was used for quantification of mitochondrial transcripts using Droplet Digital PCR. We selected ND6, CYTB, tRNA-Phe and tRNA-Gln based on their location in the mitochondrial genome, functionality and/or previous literature associating these regions with cytosine methylation. The number of mtDNA copies per oocyte/embryo was found to be similar, while methylation levels in mtDNA varied among stages. Higher total methylation levels were found mainly at 4C and 16C. In specific gene regions, higher methylation levels were also observed at 4C and 16C (ND6, CYTB and tRNA-Phe), as well as an inverse correlation with the quantity of transcripts for these regions. This is a first description of epigenetic changes occurring in mtDNA during early embryonic development. Our results indicate that methylation might regulate the mtDNA transcription at a local level, particularly around the time of embryonic genome activation.
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Metilação de DNA , DNA Mitocondrial , Gravidez , Feminino , Animais , Bovinos/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Desenvolvimento Embrionário/genética , Oócitos/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Blastocisto/metabolismoRESUMO
BACKGROUND: Intestinal inflammation, dysbiosis, intestinal permeability (IP), and bacterial translocation (BT) have been identified in patients with spondyloarthritis but the time at which they appear and their contribution to the pathogenesis of the disease is still a matter of debate. OBJECTIVES: To study the time-course of intestinal inflammation (I-Inf), IP, microbiota modification BT in a rat model of reactive arthritis, the adjuvant-induced arthritis model (AIA). METHODS: Analysis was performed at 3 phases of arthritis in control and AIA rats: preclinical phase (day 4), onset phase (day 11), and acute phase (day 28). IP was assessed by measuring levels of zonulin and ileal mRNA expression of zonulin. I-inf was assessed by lymphocyte count from rat ileum and by measuring ileal mRNA expression of proinflammatory cytokines. The integrity of the intestinal barrier was evaluated by levels of iFABP. BT and gut microbiota were assessed by LPS, soluble CD14 levels, and 16S RNA sequencing in mesenteric lymph node and by 16S rRNA sequencing in stool, respectively. RESULTS: Plasma zonulin levels increased at the preclinical and onset phase in the AIA group. Plasma levels of iFABP were increased in AIA rats at all stages of the arthritis course. The preclinical phase was characterized by a transient dysbiosis and increased mRNA ileal expression of IL-8, IL-33, and IL-17. At the onset phase, TNF-α, IL-23p19, and IL-8 mRNA expression were increased. No changes in cytokines mRNA expression were observed at the acute phase. Increased CD4+ and CD8+ T cell number was measured in the AIA ileum at day 4 and day 11. No increase in BT was observed. CONCLUSION: These data show that intestinal changes precede the development of arthritis but argue against a strict "correlative" model in which arthritis and gut changes are inseparable.
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Artrite Experimental , Interleucina-8 , Ratos , Animais , Disbiose/microbiologia , RNA Ribossômico 16S , Citocinas/metabolismo , Inflamação/patologia , Permeabilidade , RNA MensageiroRESUMO
During the screening of new N2,N4-disubstituted quinazoline 2,4-diamines as phosphodiesterase-5 inhibitors and pulmonary artery vasodilators, one N2-methyl-N4-[(thiophen-2-yl)methyl]quinazoline-2,4-diamine (compound 8) presented a greater selectivity for systemic than pulmonary vasculature. The present study aimed to characterize its vasorelaxant and hypotensive effects in Wistar rats. Vasorelaxant effects of compound 8 and underlying mechanisms were evaluated on isolated mesenteric arteries. Acute hypotensive effect was evaluated in anesthetized rats. Additionally, cell viability and cytochrome P450 (CYP) activities were studied in rat isolated hepatocytes. Nifedipine was used as a comparator. Compound 8 induced a strong vasorelaxant effect, similar to nifedipine. This was unaffected by endothelium removal but was decreased by inhibitors of guanylate cyclase (ODQ) and KCa channel (iberiotoxin). Compound 8 enhanced sodium nitroprusside-induced relaxation, but inhibited vasoconstriction evoked by α1-adrenergic receptor activation and extracellular Ca2+ influx via receptor-operated Ca2+ channels. Acute intravenous infusion of compound 8 (0.05 and 0.1 mg/kg) produced hypotension. It showed similar potency to nifedipine for lowering diastolic and mean arterial blood pressure, but less so for the effect on systolic blood pressure. Compound 8 had no effect on hepatocyte viability and CYP activities except at high concentration (10 µM) at which a weak inhibitory effect on CYP1A and 3A was observed. In conclusion, this study identified a N2-methyl-N4-[(thiophen-2-yl)methyl]quinazoline-2,4-diamine with a potent vasodilator effect on resistance vessels, leading to an acute hypotensive effect and a low risk of liver toxicity or drug-drug interactions. These vascular effects were mediated mainly through sGC/cGMP pathway, opening of KCa channels, and inhibition of calcium entry.
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Artérias Mesentéricas , Vasodilatadores/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , Quinazolinas/química , Quinazolinas/isolamento & purificação , Quinazolinas/farmacologia , Diaminas/química , Artérias Mesentéricas/química , Hipotensão , Masculino , Animais , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that has a heavy social and economic impact on all societies and for which there is still no cure. Multitarget-directed ligands (MTDLs) seem to be a promising therapeutic strategy for finding an effective treatment for this disease. For this purpose, new MTDLs were designed and synthesized in three steps by simple and cost-efficient procedures targeting calcium channel blockade, cholinesterase inhibition, and antioxidant activity. The biological and physicochemical results collected in this study allowed us the identification two sulfonamide-dihydropyridine hybrids showing simultaneous cholinesterase inhibition, calcium channel blockade, antioxidant capacity and Nrf2-ARE activating effect, that deserve to be further investigated for AD therapy.
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Doença de Alzheimer , Di-Hidropiridinas , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Ligantes , Doenças Neurodegenerativas/tratamento farmacológico , Di-Hidropiridinas/farmacologia , Di-Hidropiridinas/uso terapêutico , Canais de Cálcio , Colinesterases/metabolismo , Acetilcolinesterase/metabolismoRESUMO
OBJECTIVE: Epidural hematoma (EDH) has rarely been studied specifically in infants. The objective of this study was to investigate the outcomes of patients aged < 18 months (infants) with EDH. METHODS: The authors conducted a single-center retrospective study of 48 infants aged less than 18 months who underwent an operation for a supratentorial EDH in the last decade. Clinical, radiological, and biological variables were used in a statistical analysis to identify factors predictive of radiological and clinical outcome. RESULTS: Forty-seven patients were included in the final analysis. Seventeen children (36%) had cerebral ischemia on postoperative imaging, either due to stroke (cerebral herniation) or by local compression. Factors associated with ischemia after multivariate logistic regression were the presence of an initial neurological deficit (76% vs 27%, p = 0.03), low platelet count (mean 192 vs 267 per mm3, p = 0.01), low fibrinogen level (mean 1.4 vs 2.2 g/L, p = 0.04) and long intubation time (mean 65.7 vs 10.1 hours, p = 0.03). Cerebral ischemia on MRI was predictive of a poor clinical outcome. CONCLUSIONS: Infants with EDH have a low mortality rate but a high risk of cerebral ischemia, along with long-term neurological sequelae.
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Everolimus is the first oral targeted therapy widely used in advanced HR+/HER2- breast cancer. We sought to evaluate the impact of everolimus-based therapy on overall survival in the ESME-MBC database, a national metastatic breast cancer cohort that collects retrospective data using clinical trial-like methodology including quality assessments. We compared 1693 patients having received everolimus to 5928 patients not exposed to everolimus in the same period. Overall survival was evaluated according to treatment line, and a propensity score with the inverse probability of treatment weighting method was built to adjust for differences between groups. Crude and landmark overall survival analyses were all compatible with a benefit from everolimus-based therapy. Adjusted hazard ratios for overall survival were 0.34 (95% CI: 0.16-0.72, p = 0.0054), 0.34 (95% CI: 0.22-0.52, p < 0.0001), and 0.23 (95% CI: 0.14-0.36, p < 0.0001) for patients treated with everolimus in line 1, 2, and 3 and beyond, respectively. No clinically relevant benefit on progression-free survival was observed. Causes for everolimus discontinuation were progressive disease (56.2%), adverse events (27.7%), and other miscellaneous reasons. Despite the limitations inherent to such retrospective studies, these results suggest that adding everolimus-based therapy to the therapeutic sequences in patients with advanced HR+/HER2- breast cancer may favorably affect overall survival.
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Rheumatoid arthritis (RA) is associated with excessive cardiovascular mortality secondary to premature atherosclerosis, in which endothelial activation (EA) plays a central role. EA is characterized by loss of vascular integrity, expression of leucocyte adhesion molecules, transition from antithrombotic to prothrombotic phenotype, cytokines production, shedding of membrane microparticles and recruitment of endothelial progenitor cells. As EA is an early event in atherogenesis, circulating markers of EA are putative markers of vascular pathology and cardiovascular (CV) risk. After a presentation of biology of EA, the present review analyzed the available data regarding changes in EA markers in RA in link with the vascular pathology and CV events, discussed their relevance as biomarkers of CV risk and proposed future directions.
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Artrite Reumatoide , Aterosclerose , Doenças Cardiovasculares , Humanos , Fatores de Risco , Doenças Cardiovasculares/metabolismo , Endotélio Vascular/metabolismo , Artrite Reumatoide/metabolismo , Aterosclerose/metabolismo , Fatores de Risco de Doenças Cardíacas , Biomarcadores/metabolismoRESUMO
The gastrointestinal tract represents one of primary routes of entry for many nanomaterials. Their size in the nanometer range and their high surface area confer them very interesting properties as food additives. They are used as texturizing, opacifying or anticaking agents. Food packaging contains nanomaterials with antimicrobial properties. Humans are also orally exposed to nanoparticles (NPs) present in the air or drinking water. Ingested NPs can then reach the intestinal lumen and interact with the gastrointestinal fluids, microbiota, mucus layers and the epithelial barrier, allowing a potential translocation. The toxicological profile of ingested NPs is still unclear due to their variety in terms of composition and physicochemical properties as well as the limited number of investigations. Their unique properties related to their small size could however affect the intestinal ecosystem but also the physical and functional properties of the intestinal barrier. This review focuses on the fate of ingested organic and inorganic NPs in the intestinal lumen and their toxicity on the microbiota and epithelial cells.
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Nanopartículas , Nanoestruturas , Humanos , Ecossistema , Nanopartículas/toxicidade , Nanopartículas/química , Intestinos , Trato Gastrointestinal , Nanoestruturas/químicaRESUMO
Although placental small extracellular vesicles (sEVs) are extensively studied in the context of pregnancy, little is known about their role during viral congenital infection, especially at the beginning of pregnancy. In this study, we examined the consequences of human cytomegalovirus (hCMV) infection on sEVs production, composition, and function using an immortalized human cytotrophoblast cell line derived from first trimester placenta. By combining complementary approaches of biochemistry, electron microscopy, and quantitative proteomic analysis, we showed that hCMV infection increases the yield of sEVs produced by cytotrophoblasts and modifies their protein content towards a potential proviral phenotype. We further demonstrate that sEVs secreted by hCMV-infected cytotrophoblasts potentiate infection in naive recipient cells of fetal origin, including human neural stem cells. Importantly, these functional consequences are also observed with sEVs prepared from an ex vivo model of infected histocultures from early placenta. Based on these findings, we propose that placental sEVs could be important actors favoring viral dissemination to the fetal brain during hCMV congenital infection.
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Infecções por Citomegalovirus , Vesículas Extracelulares , Citomegalovirus/genética , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Placenta , Gravidez , ProteômicaRESUMO
Phosphodiesterase 5 (PDE5) inhibitors are an attractive option among the currently available therapies in the management of pulmonary arterial hypertension (PAH). Good selectivity for PDE5 is associated with reduced side effects and greater vasorelaxant effect on pulmonary arteries (PA). This study investigated the vasorelaxant effects of a series of quinazoline-based PDE5 inhibitors and their precise mechanisms action using rat isolated PA and aorta, as compared to sildenafil. Their effects on rat hepatocytes (viability and CYP activities) were also evaluated. Compounds 5 and 11 displayed lower human PDE5 IC50 of the analogs studied here and induced a greater relaxant effect on PA (EC50 0.94 ± 0.30 and 1.03 ± 0.23 µM, respectively). As compared to sildenafil (EC50 = 0.05 ± 0.02 µM on PA), the relaxant effect of 5 and 11 on PA was lower but their selectivity for PA compared to aorta was higher. The effects of 5 and 11 were reduced by NG-nitro-L-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one, but not by indomethacin or potassium channels blockers. They also enhanced the relaxant effect of sodium nitroprusside, and inhibited extracellular Ca2+ influx and intracellular Ca2+release. Compounds 5 and 11 did not reduce hepatocyte viability except at concentration > 10 µM, inhibited CYP3A at 10 µM, like sildenafil, but did not induce CYP1A. In conclusion, this study identified 2 quinazoline analogues with good PDE5 inhibitory activity and good selectivity for the pulmonary vasculature. Their relaxant effect involves both the potentiation of nitric oxide-sGC-cGMP pathway and calcium inhibition. These compounds are potential leads for developing new drugs for PAH.
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Inibidores da Fosfodiesterase 5 , Vasodilatadores , Animais , Humanos , Ratos , Vasodilatadores/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Cálcio/metabolismo , Citrato de Sildenafila/farmacologia , Artéria Pulmonar , Vasodilatação , Quinazolinas/farmacologia , GMP Cíclico/metabolismoRESUMO
Usutu virus (USUV) is a neurotropic mosquito-borne flavivirus that has dispersed quickly in Europe these past years. This arbovirus mainly follows an enzootic cycle involving mosquitoes and birds, but can also infect other mammals, causing notably sporadic cases in humans. Although it is mainly asymptomatic or responsible for mild clinical symptoms, USUV has been associated with neurological disorders, such as encephalitis and meningoencephalitis, highlighting the potential health threat of this virus. Among the different transmission routes described for other flaviviruses, the capacity for some of them to be transmitted vertically has been demonstrated, notably for Zika virus or West Nile virus, which are closely related to USUV. To evaluate the ability of USUV to replicate in the placenta and gain access to the fetus, we combined the use of several trophoblast model cell lines, ex vivo human placental explant cultures from first and third trimester of pregnancy, and in vivo USUV-infected pregnant mice. Our data demonstrate that human placental cells and tissues are permissive to USUV replication, and suggest that viral transmission can occur in mice during gestation. Hence, our observations suggest that USUV could be efficiently transmitted by the vertical route.
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Culicidae , Infecções por Flavivirus , Flavivirus , Vírus do Nilo Ocidental , Infecção por Zika virus , Zika virus , Animais , Feminino , Humanos , Camundongos , Placenta , GravidezRESUMO
Titanium dioxide (TiO2) is one of the most commonly used nanomaterials in the world. Additive E171, which is used in the food industry, contains a nanometric particle fraction of TiO2. Oral exposure of humans to these nanoparticles (NPs) is intensive, leading to the question of their impact on health. Daily oral intake by rats of amounts of E171 that are relevant to human intake has been associated with an increased risk of chronic intestinal inflammation and carcinogenesis. Due to their food preferences, children are very exposed to this NP. Furthermore, maternal-foetal transfer of TiO2 NPs during pregnancy, as well as exposure of the offspring by breastfeeding, have been recently described. In France, the use of E171 in the production of foodstuffs was suspended in January 2020 as a precautionary measure. To provide some answers to this public health problem and help global regulatory agencies finalize their decisions, we reviewed in vitro and in vivo studies that address the effects of TiO2 NPs through oral exposure, especially their effects on the gastrointestinal tract, one of the most exposed tissues. Our review also highlights the effects of exposure on the offspring during pregnancy and by breastfeeding.
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Nanopartículas Metálicas , Nanopartículas , Animais , Criança , Ingestão de Alimentos , Feminino , Aditivos Alimentares , Humanos , Inflamação , Nanopartículas/toxicidade , Gravidez , Ratos , Titânio/toxicidadeRESUMO
BACKGROUND/OBJECTIVES: We observed isolated cases of perialar intertrigo in children and teenagers that did not appear to correspond to any known clinical entity. The objective of this study was to describe the clinical features of this dermatosis and the clinical characteristics of the patients. METHODS: We conducted a prospective, multicenter cohort study in France from August 2017 to November 2019. All the patients under 18 years of age with chronic perinasal intertrigo were included. A standardized questionnaire detailing the clinical characteristics of the patients and the description of the intertrigo. If possible, a Wood's lamp examination of the intertrigo was done. RESULTS: Forty-one patients were included (25 boys and 16 girls, average age: 12.1 years). Intertrigo was bilateral in 38 patients (93%). The majority of patients had no symptoms (54%). Pruritus was present in 39% of cases. Orange red follicular fluorescence was present in the perialar region on Wood's light examination in 78% of cases with active fluorescence. The presumptive diagnoses suggested by the investigators were acne (24.4%), seborrheic dermatitis (19.5%), rosacea (9.8%), psoriasis (9.8%) and perioral dermatitis (7.3%). No diagnosis was proposed in 22% of the cases. CONCLUSIONS: We describe a previously undescribed clinical sign which is characterized by a chronic bilateral erythematous intertrigo located in the perialar region. It can be isolated or associated with various facial dermatoses.
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Intertrigo , Psoríase , Rosácea , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Intertrigo/diagnóstico , Masculino , Estudos Prospectivos , Psoríase/diagnósticoRESUMO
The E551 food additive is composed of synthetic amorphous silica particles. The current regulation does not mention any specifications regarding their size and granulometric distribution, thus allowing the presence of silica nanoparticles despite their potential toxicity. The digestion process could modify their physicochemical properties and then influence their toxicological profile. After physicochemical characterization, subacute toxicity of engineered silica nanoparticles from 20 to 200 nm, native and digested E551 additives were evaluated from in vitro models of the intestinal barrier. Single cultures and a co-culture of enterocytes and mucus-secreting cells were established to investigate the mucus role. Toxicological endpoints including cytotoxicity, ROS production, intestinal permeability increase, and actin filament disruption were addressed after a 7-day exposure. The results showed a size-dependent effect of silica nanoparticles on cytotoxicity and intestinal permeability. A time-dependent disruption of actin filaments was observed in Caco-2 cells. The mucus layer spread on the HT29-MTX single culture acted as an efficient protective barrier while in the co-culture, small nanoparticles were able to cross it to reach the cells. From a hydrodynamic diameter of 70 nm, nanoparticles were not internalized in the intestinal cells, even in mucus-free models. Digestion did not affect the physicochemical properties of the additive. Due to a mean hydrodynamic diameter close to 200 nm, both native and digested E551 additives did not induce any toxic effect in intestinal barrier models. This study emphasized a cutoff size of 70 nm from which the interactions of the E551 additive with intestinal cells would be limited.