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1.
Cell Biosci ; 14(1): 101, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095802

RESUMEN

BACKGROUND: COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear. METHODS: The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo. RESULTS: Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs. CONCLUSIONS: In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.

2.
Metabolites ; 14(7)2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39057703

RESUMEN

This prospective study in Hong Kong aimed at identifying prognostic metabolomic and immunologic biomarkers for Coronavirus Disease 2019 (COVID-19). We examined 327 patients, mean age 55 (19-89) years, in whom 33.6% were infected with Omicron and 66.4% were infected with earlier variants. The effect size of disease severity on metabolome outweighed others including age, gender, peak C-reactive protein (CRP), vitamin D and peak viral levels. Sixty-five metabolites demonstrated strong associations and the majority (54, 83.1%) were downregulated in severe disease (z score: -3.30 to -8.61). Ten cytokines/chemokines demonstrated strong associations (p < 0.001), and all were upregulated in severe disease. Multiple pairs of metabolomic/immunologic biomarkers showed significant correlations. Fourteen metabolites had the area under the receiver operating characteristic curve (AUC) > 0.8, suggesting a high predictive value. Three metabolites carried high sensitivity for severe disease: triglycerides in medium high-density lipoprotein (MHDL) (sensitivity: 0.94), free cholesterol-to-total lipids ratio in very small very-low-density lipoprotein (VLDL) (0.93), cholesteryl esters-to-total lipids ratio in chylomicrons and extremely large VLDL (0.92);whereas metabolites with the highest specificity were creatinine (specificity: 0.94), phospholipids in large VLDL (0.94) and triglycerides-to-total lipids ratio in large VLDL (0.93). Five cytokines/chemokines, namely, interleukin (IL)-6, IL-18, IL-10, macrophage inflammatory protein (MIP)-1b and tumour necrosis factor (TNF)-a, had AUC > 0.8. In conclusion, we demonstrated a tight interaction and prognostic potential of metabolomic and immunologic biomarkers enabling an outcome-based patient stratification.

3.
Environ Sci Technol ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39016874

RESUMEN

Emerging aryl organophosphate esters (aryl-OPEs) have been employed as substitutes for organohalogen flame retardants in recent years; however, their environmental occurrence and associated impacts in urban estuarine sediments have not been adequately investigated, impeding regulatory decision-making. Herein, field-based investigations and modeling based on surface sediment and sediment core analysis were employed to uncover the historical pollution and current environmental impacts of aryl-OPEs in the Pearl River Estuary, South China. Our results revealed a substantial increase in aryl-OPE emission, particularly emerging aryl-OPEs, through sediment transport to the estuary since the 2000s. The emerging aryl-OPEs comprised 83% of the total annual input in the past decade, with an average annual input of 155,000 g. Additionally, the emerging-to-traditional aryl-OPE concentration ratios increased with decreasing distance from the shore, peaking in the highly urbanized riverine outlets. These findings indicate that inventories of emerging aryl-OPEs are likely increasing in estuarine sediments and their emissions are surpassing those of traditional aryl-OPEs. Our risk-based priority screening approach indicates that some emerging aryl-OPEs, particularly bisphenol A bis(diphenyl phosphate), can pose a higher environmental risk than traditional aryl-OPEs in estuarine sediments. Overall, our study highlights the importance of recognizing the environmental impacts of emerging aryl-OPEs.

4.
Environ Sci Technol ; 58(29): 12933-12942, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39003765

RESUMEN

Perfluoroethylcyclohexane sulfonate (PFECHS) is an emerging per- and polyfluoroalkyl substance used to replace perfluorooctane sulfonate (PFOS), mainly in aircraft hydraulic fluids. However, previous research indicates the potential neurotoxicity of this replacement chemical. In this study, marine medaka (Oryzias melastigma) was exposed to environmentally relevant concentrations of PFECHS (concentrations: 0, 0.08, 0.26, and 0.91 µg/L) from the embryonic stage for 90 days. After exposure, the brain and eyes of the medaka were collected to investigate the bioconcentration potential of PFECHS stereoisomers and their effects on the nervous systems. The determined bioconcentration factors (BCFs) of PFECHS ranged from 324 ± 97 to 435 ± 89 L/kg and from 454 ± 60 to 576 ± 86 L/kg in the brain and eyes of medaka, respectively. The BCFs of trans-PFECHS were higher than those of cis-PFECHS. PFECHS exposure significantly altered γ-aminobutyric acid (GABA) levels in the medaka brain and disrupted the GABAergic system, as revealed by proteomics, implying that PFECHS can disturb neural signal transduction like PFOS. PFECHS exposure resulted in significant alterations in multiple proteins associated with eye function in medaka. Abnormal locomotion was observed in PFECHS-exposed medaka larvae, which was rescued by adding exogenous GABA, suggesting the involvement of disrupted GABA signaling pathways in PFECHS neurotoxicity.


Asunto(s)
Oryzias , Animales , Oryzias/metabolismo , Contaminantes Químicos del Agua/toxicidad
5.
Mar Pollut Bull ; 205: 116635, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38936000

RESUMEN

This study provided a systematic investigation of microplastics in Hong Kong's surface marine waters during the pandemic from 2019 to 2021. Microplastics (2.07 ± 4.00 particles/m3) exhibited significant temporal variations with higher abundance in the wet season, without a consistent trend after the mandatory mask-wearing requirement was announced. The impact of pandemic restrictions on microplastic distribution was found to be relatively minor. However, significant correlations between microplastic abundances and rainfall highlighted the substantial contribution of local emissions through surface runoff. Notably, sites in closer proximity to the Pearl River Delta exhibited higher microplastic abundances, indicating their association with emission sources. The influence of rainfall and adverse weather on marine microplastic loads demonstrated different sensitivities among various locations but can generally last for one month. These results revealed the impact of seasonal rainfall on coastal microplastics and emphasized the need for efforts to reduce microplastic discharge from land-based sources.


Asunto(s)
Monitoreo del Ambiente , Microplásticos , Lluvia , Ríos , Contaminantes Químicos del Agua , Hong Kong , Contaminantes Químicos del Agua/análisis , Microplásticos/análisis , Ríos/química , Agua de Mar/química , Estaciones del Año
6.
Curr Pediatr Rev ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38778597

RESUMEN

BACKGROUND: The COVID-19 global pandemic was caused by a novel coronavirus (SARS-CoV-2), which then became an endemic infection. COVID refers to the World Health Organization's coined acronym for coronavirus disease. CASE PRESENTATION: We have, herein, reported three cases of coronavirus diseases that could have been misdiagnosed as COVID-19. All of these families reported previous COVID-19 infection based on self-administered Rapid Antigen Testing (RAT) and completed a period of home isolation. In the current presentation, one child had an RSV-associated asthma attack, one had norovirus gastritis, and another had an infection with Campylobacter and E. coli. NL63, OC43, and 229E, respectively, were found by PCR in these patients. DISCUSSION: Seven human coronaviruses cause infectious diseases, including in children. Confusion and issues associated with coronavirus disease diagnosis by Polymerase Chain Reaction (PCR) testing and Rapid Antigen Test (RAT) may arise. Some RATs are Antigen Fluorescent Immunoassays (FIA) that target monoclonal antibodies for the detection of viral nucleocapsid protein. Others target the non-nucleocapsid proteins. False positivity is possible. False negativity is also possible if the specimen's antigen level is below the test's detection limit. RAT results usually remain positive for 6 to 7 days, but they may stay positive as long as 2 weeks. Stigmatization with the COVID-19 diagnosis may occur. The PCR test is a highly sensitive 'gold standard' for the detection of COVID-19, but it can also detect non-infectious individuals' fragmented non-infectious viral nucleic acids, and could be positive for a long period. An individual may be tested positive for a few weeks to months after the individual becomes non-infectious. CONCLUSION: The cases presented here had coronavirus diseases other than COVID-19. Coronavirus diseases can be caused by coronavirus variants other than SARS-CoV-2. Co-infections with other pathogens are present in these diseases. PCR testing of non-COVID-19 diseases may help in the accurate diagnosis of these ailments and respiratory co-infections.

7.
NPJ Biofilms Microbiomes ; 10(1): 39, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589501

RESUMEN

Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/ß-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Microbiota , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Epigenómica , Disbiosis , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Bacterias , Fusobacterium nucleatum , Neoplasias de Cabeza y Cuello/genética , Epigénesis Genética , Microambiente Tumoral
8.
J Med Virol ; 96(2): e29460, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38348874

RESUMEN

A cross-sectional study in 2021-23 collected oral rinse gargle samples from an human papillomaviruses (HPV) vaccine-naïve general adult population in Hong Kong. HPV was detected by a PCR using SPF10 primers, and genotyped by a linear array covering 25 genotypes. Epidemiologic information including sociodemographics, medical history, oral health, and sexual behavior were collected by a self-administered questionnaire. Altogether, 2323 subjects aged 18-75 (median 47) years with 50.1% male were recruited. The prevalence for oral HPV infection with all genotypes combined, high-risk, and low-risk genotypes was 1.5%, 0.7%, and 0.7%, respectively; and with no statistically significant difference between participant gender. The prevalence increased with age and was highest in women at 45-54 years (2.7% for all genotypes combined), and highest in men aged >64 years (4.1% for all genotypes combined). HPV52 was the most common genotype among all participants. Univariate analysis suggested more lifetime sexual or oral sexual partners as risk factors, but they did not reach statistical significance upon multivariate analysis; whereas higher educational level had an independent protective effect. To conclude, oral HPV prevalence increased with age in Hong Kong. Strategies to prevent oral HPV infection and the associated cancers are urgently needed.


Asunto(s)
Infecciones por Papillomavirus , Adulto , Humanos , Masculino , Femenino , Hong Kong/epidemiología , Infecciones por Papillomavirus/epidemiología , Prevalencia , Estudios Transversales , Conducta Sexual , Factores de Riesgo , Papillomaviridae/genética , Genotipo
9.
Cancers (Basel) ; 16(1)2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38201653

RESUMEN

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers. Archived tumor tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010-2020. The HPV-positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016-2020 vs. 40.4% (19/47) in 2010-2015, p = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, p = 0.006), but no significant difference was observed between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.

10.
Environ Int ; 184: 108434, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38237506

RESUMEN

Pharmaceuticals are receiving increasing attention as emerging contaminants in the aquatic environment. Herein, we investigated the occurrence of 11 antidepressants, 6 antihistamines and 4 metabolites in treated wastewater effluents, rivers, stormwater, and seawater in Hong Kong, with special focus on chirality. The average levels of ∑pharmaceuticals ranged from 0.525 to 1070 ng/L in all samples and the total annual mass load of target pharmaceuticals in the marine environment of Hong Kong was 756 kg/y. Antihistamines accounted for >80 % of ∑pharmaceuticals, with diphenhydramine and fexofenadine being predominant. The occurrence and enantiomeric profiles of brompheniramine and promethazine sulfoxide were reported in global natural waters for the first time. Among chiral pharmaceuticals, mirtazapine and fexofenadine exhibited R-preference, while others mostly exhibited S-preference, implying that the ecological risks derived from achiral data for chiral pharmaceuticals may be biased. The joint probabilistic risk assessment of fluoxetine revealed that R-fluoxetine and rac-fluoxetine presented different ecological risks from that of S-fluoxetine; Such assessment also revealed that target pharmaceuticals posed only minimal to low risks, except that diphenhydramine posed an intermediate risk. As estimated, 10 % aquatic species will be affected when the environmental level of diphenhydramine exceeds 7.40 ng/L, which was seen in 46.9 % samples. Collectively, this study highlights further investigations on the enantioselectivity of chiral pharmaceuticals, particularly on environmental behavior and ecotoxicity using local aquatic species as target organisms.


Asunto(s)
Fluoxetina , Terfenadina/análogos & derivados , Contaminantes Químicos del Agua , Fluoxetina/toxicidad , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Antidepresivos , Antagonistas de los Receptores Histamínicos , Difenhidramina , Medición de Riesgo , Ríos , Preparaciones Farmacéuticas
11.
Environ Sci Technol ; 58(2): 1076-1087, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38166396

RESUMEN

The unintended exposure of humans and animals to isothiazolinones has led to an increasing concern regarding their health hazards. Isothiazolinones were previously found to disrupt reproductive endocrine homeostasis. However, the long-term reproductive toxicity and underlying mechanism remain unclear. In this study, life-cycle exposure of medaka to dichlorocthylisothiazolinone (DCOIT), a representative isothiazolinone, significantly stimulated the gonadotropin releasing hormone receptor (GnRHR)-mediated synthesis of follicle stimulating hormone and luteinizing hormone in the brain. Chem-Seq and proteome analyses revealed disturbances in the G-protein-coupled receptor, MAPK, and Ca2+ signaling cascades by DCOIT. The G protein αi subunit was identified as the binding target of DCOIT. Gαi bound by DCOIT had an enhanced affinity for the mitochondrial calcium uniporter, consequently changing Ca2+ subcellular compartmentalization. Stimulation of Ca2+ release from the endoplasmic reticulum and blockage of Ca2+ uptake into the mitochondria resulted in a considerably higher cytoplasmic Ca2+ concentration, which then activated the phosphorylation of MEK and ERK to dysregulate hormone synthesis. Overall, by comprehensively integrating in vivo, ex vivo, in silico, and in vitro evidence, this study proposes a new mode of endocrine disrupting toxicity based on isothiazolinones, which is expected to aid the risk assessment of the chemical library and favor the mechanism-driven design of safer alternatives.


Asunto(s)
Receptores Acoplados a Proteínas G , Transducción de Señal , Humanos , Animales , Transducción de Señal/fisiología , Reproducción , Hormona Liberadora de Gonadotropina/fisiología
12.
J Hazard Mater ; 465: 133176, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38070264

RESUMEN

The application of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) as an antifouling biocide causes high toxicity to non-target marine organisms. To examine the developmental cardiotoxicity and mechanisms of DCOIT, we concurrently performed sub-chronic exposure and life-cycle exposure experiments using marine medaka embryos. After sub-chronic exposure to DCOIT at 1, 3, 10, and 33 µg/L, cardiac defects were caused by upregulation of cardiac gene transcriptions, decreasing heart size, and accelerating heartbeat. Hyperthyroidism in medaka larvae was identified as the cause of developmental cardiotoxicity of DCOIT sub-chronic exposure. In addition, parental life-cycle exposure to 1, 3, and 10 µg/L DCOIT led to transgenerational impairment of cardiogenesis in offspring medaka. A crossbreeding strategy discriminated a concentration-dependent mechanism of transgenerational cardiotoxicity. At 1 µg/L, the DCOIT-exposed female parent transferred a significantly higher amount of triiodothyronine (T3) hormone to offspring, corresponding to an accelerated heart rate. However, DCOIT at higher exposure concentrations modified the methylome imprinting in larval offspring, which was associated with cardiac dysfunction. Overall, the findings provide novel insights into the developmental cardiotoxicity of DCOIT. The high risks of DCOIT-even at environmentally realistic concentrations-raise concerns about its applicability as an antifoulant in a marine environment.


Asunto(s)
Oryzias , Contaminantes Químicos del Agua , Animales , Femenino , Oryzias/fisiología , Cardiotoxicidad , Contaminantes Químicos del Agua/toxicidad , Tiazoles/toxicidad , Estadios del Ciclo de Vida , Larva
13.
Environ Int ; 181: 108308, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37939439

RESUMEN

Isothiazolinones are extensively used as preservatives and disinfectants in personal care products and household items. The unintended exposure of humans and animals to isothiazolinones has led to increasing concerns about their health hazards. The compound 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT), a representative isothiazolinone, can simultaneously induce endocrine disruption and neurotoxicity. However, the underlying mechanisms and linkages remain unclear. Our purpose was to elucidate the role of miRNAs as the signaling communicator during the crosstalk between endocrine and nervous systems in response to DCOIT stress. H295R cells were exposed to DCOIT, after which the alterations in intracellular miRNA composition, exosome secretory machinery, and extracellular miRNA composition were examined. Then, a PC12 cell line of neuronal differentiation potential was cultured with the extract of extracellular miRNAs from DCOIT-exposed H295R cell media to explore the functional implications in neurogenesis. The results showed that DCOIT exposure resulted in 349 differentially expressed miRNAs (DEMs) in H295R cells, which were closely related to the regulation of multiple endocrine pathways. In the media of H295R cells exposed to DCOIT, 66 DEMs were identified, showing distinct compositions compared to intracellular DEMs with only 2 common DEMs (e.g., novel-m0541-5p of inverse changes in the cell and medium). Functional annotation showed that extracellular DEMs were not only associated with sex endocrine synchronization, but were also implicated in nervous system development, morphogenesis, and tumor. Incubating PC12 cells with the extracellular exosomes (containing miRNAs) from DCOIT-exposed H295R cells significantly increased the neurite growth, promoted neuronal differentiation, and shaped the transcriptomic fingerprint, implying that miRNAs may communicate transduction of toxic information of DCOIT in endocrine system to neurons. Overall, the present findings provide novel insight into the endocrine disrupting and neural toxicity of DCOIT. The miRNAs have the potential to serve as the epigenetic mechanism of systems toxicology.


Asunto(s)
MicroARNs , Contaminantes Químicos del Agua , Animales , Ratas , Humanos , Contaminantes Químicos del Agua/toxicidad , Sistema Endocrino , Transducción de Señal , Neurogénesis , Tiazoles/toxicidad
15.
Cell Mol Life Sci ; 80(10): 278, 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37682346

RESUMEN

Human papillomavirus (HPV) encoded E7 oncoprotein plays an important role in supporting the viral productive cycle and inducing cancer phenotypes. The ability of E7 to exercise these functions, partly, depends upon its steady-state level. HPV manipulates the host de-ubiquitination pathway to maintain the stability of its viral proteins. In this study, we uncovered that HPV interacts with the host ubiquitin specific protease 7 (USP7), a universal de-ubiquitinating enzyme, leading to the stabilization of E7 oncoprotein. We observed that HPV16E7 complexes with USP7 via the E7-CR3 domain, and this E7-USP7 complex exists predominantly in the nucleus. Our results showed that USP7 stabilizes and prolongs the half-life of HPV16E7 by antagonizing ubiquitination and proteasomal degradation. Consistently, when we inhibited USP7 activity using HBX 19818, HPV16E7 protein level was reduced and its turnover was increased. We also provide evidence that HBX 19818-induced USP7 inhibition can halt HPV-mediated carcinogenesis, including cell proliferation, invasion, migration and transformation. These findings indicate that USP7 plays an essential role in stabilizing E7. The specific and potent inhibitory effects of HBX 19818 on HPV-induced carcinogenesis provide a molecular insight, suggesting the potential of targeting USP7 as a new therapeutic approach for the treatment of HPV-associated cancers.


Asunto(s)
Infecciones por Papillomavirus , Humanos , Peptidasa Específica de Ubiquitina 7 , Carcinogénesis , Núcleo Celular , Proliferación Celular , Virus del Papiloma Humano
16.
Environ Sci Technol ; 57(40): 14904-14916, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37774144

RESUMEN

Current toxicological data of perfluoroalkyl acids (PFAAs) are disparate under similar exposure scenarios. To find the cause of the conflicting data, this study examined the influence of chemical speciation on the toxicity of representative PFAAs, including perfluorooctanoic acid (PFOA), perfluorobutane carboxylic acid (PFBA), and perfluorobutanesulfonic acid (PFBS). Zebrafish embryos were acutely exposed to PFAA, PFAA salt, and a pH-negative control, after which the developmental impairment and mechanisms were explored. The results showed that PFAAs were generally more toxic than the corresponding pH control, indicating that the embryonic toxicity of PFAAs was mainly caused by the pollutants themselves. In contrast to the high toxicity of PFAAs, PFAA salts only exhibited mild hazards to zebrafish embryos. Fingerprinting the changes along the thyroidal axis demonstrated distinct modes of endocrine disruption for PFAAs and PFAA salts. Furthermore, biolayer interferometry monitoring found that PFOA and PFBS acids bound more strongly with albumin proteins than did their salts. Accordingly, the acid of PFAAs accumulated significantly higher concentrations than their salt counterparts. The present findings highlight the importance of chemical forms to the outcome of developmental toxicity, calling for the discriminative risk assessment and management of PFAAs and salts.

17.
Microbiol Spectr ; : e0118123, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37750685

RESUMEN

Rhinovirus (RV) is the leading pathogen causing childhood wheezing, with rhinovirus C (RV-C) species reported to cause asthma exacerbation. Allele A of single-nucleotide polymorphism (SNP) CDHR3_rs6967330 upregulates epithelial expression of RV-C receptors which results in more severe asthma exacerbations in children. Nevertheless, there are limited data on interactions between CDHR3 variants and their impact on severity of RV-related pediatric respiratory tract infections (RTIs). Medical records of RV-related RTIs in children aged below 18 years who were hospitalized in two public hospitals in 2015-2016 were independently reviewed by two paediatricians. Archived nasopharyngeal aspirates were retrieved for RV detection and sequencing as well as CDHR3 genotyping. HaploView v.5.0 and generalized multifactor dimensionality reduction (GMDR) analysis were employed for haplotypic assignment and gene-environment interaction analyses. Among 1019 studied cases, our results confirmed the relationship between RV-C species and more severe RTIs. Besides the top risk variant rs6967330-A, we identified rs140154310-T to be associated with RV-C susceptibility under the additive model [odds ratio (OR) 2.53, 95% CI 1.15-5.56; P = 0.021]. Rs140154310 was associated with wheezing illness (OR 2.38, 95% CI 1.12-5.04; P = 0.024), with such association being stronger in subjects who wheezed due to RV-C infections (OR 2.71, 95% CI 1.32-5.58; P = 0.007). Haplotype GAG constructed from rs4730125, rs6967330, and rs73195665 was associated with increased risk of RV-C infection (OR 1.71, 95% CI 1.11-2.65; P = 0.016) and oxygen supplementation (OR 1.93, 95% CI 1.13-3.30; P = 0.016). GMDR analyses revealed epistatic interaction between rs140154310 and rs6967330 of CDHR3 for RV-C infection (P = 0.001), RV-C-associated lower RTI (P = 0.004), and RV-C-associated wheeze (P = 0.007). There was synergistic gene-environmental interaction between rs3887998 and RV-C for more severe clinical outcomes (P < 0.001). To conclude, rs140154310-T is another risk variant for RV-C susceptibility and more severe RTIs. Synergistic epistatic interaction is found between CDHR3 SNPs and RV-C for RTI severity, which is likely mediated by susceptibility to RV-C. Haplotypic analysis and GMDR should be included in identifying prediction models of CDHR3 for childhood asthma and RTIs. IMPORTANCE This case-control study investigated the interaction between CDHR3 genotypes and rhinovirus (RV) species on disease severity in Hong Kong children hospitalized for respiratory tract infection (RTI). There were synergistic effects between RV-C and CDHR3 SNPs for RTI severity, which was mainly driven by RV-C. Specifically, rs6967330 and rs140154310 alone and their epistatic interaction were associated with RV-C-related and severe RTIs in our subjects. Therefore, genotyping of CDHR3 SNPs may help physicians formulate prediction models for severity of RV-associated RTIs.

18.
mSystems ; 8(5): e0052123, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37646516

RESUMEN

IMPORTANCE: Eczema is a major allergic disease in children, which is particularly prevalent in Chinese children during their first year of life. In this study, we showed that alterations in the infant gut microbiota precede the development of eczema in a prospective Chinese cohort. In particular, we discovered enrichments of the genera Clostridium sensu stricto 1 and Finegoldia in the cases at 3 and 1 month of age, respectively, which may represent potential targets for intervention to prevent eczema. Besides, we identified a depletion of Bacteroides from 1 to 6 months of age and an enrichment of Clostridium sensu stricto 1 at 3 months in the eczema cases, patterns also observed in C-section-born infants within the same time frames, providing first evidence to support a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema in infancy.


Asunto(s)
Eccema , Microbioma Gastrointestinal , Lactante , Niño , Embarazo , Femenino , Humanos , Estudios Prospectivos , Heces , Eccema/epidemiología , Clostridium , China/epidemiología
19.
Curr Pediatr Rev ; 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37605390

RESUMEN

BACKGROUND: From time to time, physicians face challenging diagnostic and therapeutic issues concerning the acute management of children with viral encephalitis. OBJECTIVE: The aim of this article is to provide an updated narrative review on the similarities and differences between SARS-CoV-2 and influenza encephalitis. METHODS: A PubMed search was performed with the function "Clinical Queries" using the key terms "SARS-CoV-2" OR "Influenza" AND "Encephalitis". The search strategy included meta-analyses, clinical trials, randomized controlled trials, reviews and observational studies. The search was restricted to the English literature and pediatric population. This article compares similarities and contrasts between SARS-CoV-2 and influenza-associated encephalitis. RESULTS: Encephalitis is an uncommon manifestation of both influenza and SARS-CoV-2. Both vi-ruses are associated with fever and respiratory symptoms. However, SARS-CoV-2 patients may on-ly have mild symptoms or be asymptomatic as silent carriers, rendering the disease spread difficult to control. Influenza patients usually have more severe symptomatology and are often bed bound for several days limiting its spread. Influenza is associated with seasonal and annual outbreaks, whereas SARS-CoV-2 has become endemic. Complications of encephalitis are rare in both viral infections but, when present, may carry serious morbidity and mortality. Many long-term sequelae of COVID-19 infections (long COVID-19) have been described but not with influenza infections. Mortality as-sociated with encephalitis appears higher with influenza than with SARS-CoV-2. Prophylaxis by immunization is available for both influenza and SARS-CoV-2. Specific efficacious antivirals are also available with oseltamivir for influenza and nirmatrelvir/ritonavir for SARS-CoV-2. Steroids are indicated with more severe SARS-CoV-2 but their role is not distinct in influenza disease. CONCLUSION: Encephalitis is a rare complication of influenza and SARS-CoV-2 infections. Both car-ry significant morbidity and mortality. Efficacious vaccines for prophylaxis and antivirals for treat-ment are available for both viruses.

20.
Environ Sci Technol ; 57(31): 11656-11665, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37503546

RESUMEN

Due to their prevalence in urban contaminated water, the driving factors of organophosphate esters (OPEs) need to be well examined, and their related ecological impacts should include that of their transformation products (TPs). Additionally, a robust framework needs to be developed to integrate multiple variables related to ecological impacts for improving the ecological health assessment. Therefore, OPEs and TPs in urban stormwater and wastewater in Hong Kong were analyzed to fill these gaps. The results revealed that the total concentrations of OPEs in stormwater were positively correlated with the area of transportation land. Individual TP concentrations and the mass ratios of individual TPs/OPEs were somewhat higher in sewage effluents than that in stormwater. OPEs generally showed relatively higher risk quotients than TPs; however, the total risk quotients increased by approximately 38% when TPs were factored in. Moreover, the molecular docking results suggested that the investigated TPs might cause similar endocrine disruption in marine organisms as their parent OPEs. This study employed the Toxicological-Priority-Index scheme to successfully integrate the ecological risks and endocrine-disrupting effects to refine the ecological health assessment of the exposure to OPEs and their TPs, which can better inform the authority on the prioritization for regulating these contaminants of emerging concern in urban built environments.


Asunto(s)
Retardadores de Llama , Contaminantes Químicos del Agua , Aguas del Alcantarillado , Contaminantes Químicos del Agua/análisis , Simulación del Acoplamiento Molecular , Monitoreo del Ambiente/métodos , Organofosfatos , Ésteres , China , Retardadores de Llama/análisis
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