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1.
Sci Total Environ ; 931: 173001, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38710397

RESUMO

Mining activities can potentially release high levels of Pb(II) in acid mine drainage (AMD), which thereafter poses a significant threat to ecological security. In this study, green reduced graphene oxide/silver nanoparticles (rGO/Ag NPs) were successfully synthesized via a one-step approach using a green tea extract and subsequently used as a cost-effective absorbent to remove Pb(II) from AMD. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy indicated that organic functional groups in the green tea extracts, such as C=O-C, CO, and CC, acted both as reductants and stabilizers in the synthesis of rGO/Ag NPs. In addition, the removal efficiency of Pb(II) by rGO/Ag NPs (84.2 %) was much better than either rGO (75.4 %) or Ag NPs (12.3 %) alone. Also, in real AMD, the distribution coefficient (Kd) of Pb(II) (4528 mL/g), was much higher than other heavy metal indicating the adsorbent had a high selective affinity for Pb(II). Interestingly, after five cycles of use, the removal efficiency of Pb(II) by rGO/Ag NPs from AMD actually increased from 46.4 to 65.2 % due to iron oxides (i.e., Fe2O3 and Fe3O4) being generated when rGO/Ag NPs was exposed to AMD. The removal of Pb(II) via adsorption on the rGO/Ag NPs surface involved formation of hexagonal rod-like precipitates. This work demonstrated the potential of rGO/Ag NPs to be continuously used for the removal of Pb(II) from AMD.

2.
J Environ Manage ; 358: 120817, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38593740

RESUMO

Spartina alterniflora invasion is considered a critical event affecting sediment phosphorus (P) availability and stock. However, P retention and microbial phosphate solubilization in the sediments invaded with or without S. alterniflora have not been fully investigated. In this study, a sequential fractionation method and high-throughput sequencing were used to analyze P transformation and the underlying microbial mechanisms in the sediments of no plant (NP) zone, transition (T) zone, and plant (P) zone. Results showed that except for organic phosphate (OP), total phosphate (TP), inorganic phosphate (IP), and available phosphate (AP) all followed a significant decrease trend from the NP site to the T site, and to the P site. The vertical decrease of TP, IP, and AP was also observed with an increase in soil depth. Among the six IP fractions, Fe-P, Oc-P, and Ca10-P were the predominant forms, while the presence of S. alterniflora resulted in an obvious P depletion except for Ca8-P and Al-P. Although S. alterniflora invasion did not significantly alter the alpha diversity of phosphate-solubilizing bacteria (PSB) harboring phoD gene, several PSB belonging to p_Proteobacteria, p_Planctomycetes, and p_Cyanobacteriota showed close correlations with P speciation and IP fractions. Further correlation analysis revealed that the reduced soil pH, soil TN and soil EC, and the increased soil TOC mediated by the invasion of S. alterniflora also significantly correlated to these PSB. Overall, this study elucidates the linkage between PSB and P speciation and provides new insights into understanding P retention and microbial P transformation in the coastal sediment invaded by S. alterniflora.


Assuntos
Fosfatos , Fósforo , Poaceae , Áreas Alagadas , China , Estuários , Sedimentos Geológicos/microbiologia
3.
J Environ Manage ; 356: 120544, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38471323

RESUMO

Biofilters are the important source and sink of antibiotic resistance genes (ARGs) and antibiotic resistance bacteria (ARB) in the drinking water. Current studies generally ascribed the prevalence of BAR in biofilter from the perspective of gene behavior, i.e. horizontal gene transfer (HGT), little attentions have been paid on the ARGs carrier- ARB. In this study, we proposed the hypothesis that ARB participating in pollutant metabolism processes and becoming dominant is an important way for the enrichment of ARGs. To verify this, the antibiotic resistome and bacterial functional metabolic pathways of a sand filter was profiled using heterotrophic bacterial plate counting method (HPC), high-throughput qPCR, Illumina Hiseq sequencing and PICRUSt2 functional prediction. The results illustrated a significant leakage of ARB in the effluent of the sand filter with an average absolute abundance of approximately 102-103 CFU/mL. Further contribution analysis revealed that the dominant genera, such as Acinetobacter spp., Aeromonas spp., Elizabethkingia spp., and Bacillus spp., were primary ARGs hosts, conferring resistance to multiple antibiotics including sulfamethoxazole, tetracycline and ß-lactams. Notably, these ARGs hosts were involved in nitrogen metabolism, including extracellular nitrate/nitrite transport and nitrite reduction, which are crucial in nitrification and denitrification in biofilters. For example, Acinetobacter spp., the dominant bacteria in the filter (relative abundance 69.97 %), contributed the majority of ARGs and 53.79 % of nitrite reduction function. That is, ARB can predominate by participating in the nitrogen metabolism pathways, facilitating the enrichment of ARGs. These findings provide insights into the stable presence of ARGs in biofilters from a functional metabolism perspective, offering a significant supplementary to the mechanisms of the emergence, maintenance, and transmission of BARin drinking water.


Assuntos
Antibacterianos , Água Potável , Antibacterianos/farmacologia , Antibacterianos/análise , Genes Bacterianos , Antagonistas de Receptores de Angiotensina/análise , Nitritos/análise , Resistência Microbiana a Medicamentos/genética , Inibidores da Enzima Conversora de Angiotensina/análise , Nitrogênio/análise
4.
Environ Res ; 245: 118021, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38147917

RESUMO

Saltwater intrusion in estuarine ecosystems alters microbial communities as well as biogeochemical cycling processes and has become a worldwide problem. However, the impact of salinity intrusion on the dynamics of nitrous oxide (N2O) and associated microbial community are understudied. Here, we conducted field microcosms in a tidal estuary during different months (December, April and August) using dialysis bags, and microbes inside the bags encountered a change in salinity in natural setting. We then compared N2O dynamics in the microcosms with that in natural water. Regardless of incubation environment, saltwater intrusion altered the dissolved N2O depending on the initial saturation rates of N2O. While the impact of saltwater intrusion on N2O dynamics was consistent across months, the dissolved N2O was higher in summer than in winter. The N-related microbial communities following saltwater intrusion were dominated by denitrifers, with fewer nitrifiers and bacterial taxa involved in dissimilatory nitrate reduction to ammonium. While denitrification was a significant driver of N2O dynamics in the studied estuary, nitrifier-involved denitrification contributed to the additional production of N2O, evidenced by the strong associations with amoA genes and the abundance of Nitrospira. Higher N2O concentrations in the field microcosms than in natural water limited N2O consumption in the former, given the lack of an association with nosZ gene abundance. The differences in the N2O dynamics observed between the microcosms and natural water could be that the latter comprised not only indigenous microbes but also those accompanied with saltwater intrusion, and that immigrants might be functionally rich individuals and able to perform N transformation in multiple pathways. Our work provides the first quantitative assessment of in situ N2O concentrations in an estuary subjected to a saltwater intrusion. The results highlight the importance of ecosystem size and microbial connectivity in the source-sink dynamics of N2O in changing environments.


Assuntos
Bactérias , Microbiota , Humanos , Bactérias/genética , Água , Nitratos , Óxido Nitroso , Solo
5.
Cell Death Dis ; 14(11): 783, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-38030599

RESUMO

Li-Fraumeni syndrome (LFS) is characterized by germline mutations occurring on one allele of genome guardian TP53. It is a severe cancer predisposition syndrome with a poor prognosis, partly due to the frequent development of subsequent primary tumors following DNA-damaging therapies. Here we explored, for the first time, the effectiveness of mutant p53 rescue compound in treating LFS-mimicking mice harboring a deleterious p53 mutation. Among the ten p53 hotspot mutations in IARC LFS cohorts, R282W is one of the mutations predicting the poorest survival prognosis and the earliest tumor onset. Among the six clinical-stage mutant p53 rescue compounds, arsenic trioxide (ATO) effectively restored transactivation activity to p53-R282W. We thus constructed a heterozygous Trp53 R279W (corresponding to human R282W) mouse model for the ATO treatment study. The p53R279W/+ (W/+) mice exhibited tumor onset and overall survival well mimicking the ones of human LFS. Further, 35 mg/L ATO addition in drink water significantly extended the median survival of W/+ mice (from 460 to 596 days, hazard ratio = 0.4003, P = 0.0008). In the isolated tumors from ATO-treated W/+ mice, the representative p53 targets including Cdkn1a, Mdm2, and Tigar were significantly upregulated, accompanying with a decreased level of the proliferation marker Ki67 and increased level of apoptosis marker TUNEL. Together, the non-genotoxic treatment of p53 rescue compound ATO holds promise as an alternative for LFS therapeutic.


Assuntos
Síndrome de Li-Fraumeni , Humanos , Animais , Camundongos , Síndrome de Li-Fraumeni/tratamento farmacológico , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/complicações , Proteína Supressora de Tumor p53/genética , Trióxido de Arsênio/farmacologia , Trióxido de Arsênio/uso terapêutico , Predisposição Genética para Doença , Genes p53
6.
Mar Environ Res ; 192: 106196, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37751645

RESUMO

Temperature plays an important role in affecting the physiological traits of marine plankton. In this study, we conducted an outdoor incubation experiment to investigate the effects of elevated temperature on Chl a, photosynthetic carbon fixation and the composition of plankton communities in the surface seawater around Pingtan Island, the northwest Taiwan Strait in Autumn 2022. After 3-4 days of incubation, elevated temperature (1-4 °C higher than ambient temperature) led to a decrease in Chl a concentration across all three stations, did not result in significant increases in the particulate organic carbon (POC) and nitrogen (PON) concentrations in seawater with high nitrate concentrations, whereas increased POC and PON concentrations in nitrate-limited seawater. These findings suggest that the effect of temperature on the POC and PON contents of plankton is affected by the availability of nitrate. Diatoms were the dominant phytoplankton group in all three stations. Our results indicate that ocean warming has a potential to increase the POC contents of marine plankton per volume of seawater, which may increase the ability of phytoplankton to absorb atmospheric CO2 and to alleviate global warming.


Assuntos
Nitratos , Plâncton , Fitoplâncton/fisiologia , Água do Mar , Fotossíntese , China , Oceanos e Mares , Carbono
7.
Environ Res ; 235: 116663, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37451574

RESUMO

As one of the polycyclic aromatic hydrocarbons (PAHs), naphthalene is of serious environmental concern due to its carcinogenicity, persistence and refractory degradation. In this study, a new functional biomaterial based on Burkholderia cepacia (BK) immobilized on reduced graphene oxide (rGO) was prepared, resulting in the removal of 99.0% naphthalene within 48 h. This was better than the 67.3% for free BK and 55.6% for rGO alone. Various characterizations indicated that reduced graphene oxide-Burkholderia cepacia (rGO-BK) was successfully synthesized and secreted non-toxic and degradable surfactants which participated in the degradation of naphthalene. The adsorption kinetics and degradation kinetics conformed best to non-linear pseudo-second-order and pseudo-first-order kinetic models, respectively. Demonstrated in this work is that removing naphthalene by rGO-BK involved both chemically dominated adsorption and biodegradation. As well, GC-MS analysis revealed two things: firstly, that the degraded products of naphthalene were dibutyl phthalate, diethyl phthalate, phthalic acid, and benzoic acid; and secondly, two potentially viable biodegradation pathways of naphthalene by rGO-BK could be proposed. Finally, for practical application experiment, the rGO-BK was exposed to river water samples and generated 99% removal efficiency of naphthalene, so this study offers new insights into biomaterials that can remove naphthalene.


Assuntos
Burkholderia cepacia , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Burkholderia cepacia/metabolismo , Águas Residuárias , Materiais Biocompatíveis/metabolismo , Naftalenos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Biodegradação Ambiental , Adsorção , Poluentes Químicos da Água/química
8.
Sci Transl Med ; 15(690): eabn9155, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37018419

RESUMO

Tumor suppressor p53 is inactivated by thousands of heterogeneous mutations in cancer, but their individual druggability remains largely elusive. Here, we evaluated 800 common p53 mutants for their rescue potencies by the representative generic rescue compound arsenic trioxide (ATO) in terms of transactivation activity, cell growth inhibition, and mouse tumor-suppressive activities. The rescue potencies were mainly determined by the solvent accessibility of the mutated residue, a key factor determining whether a mutation is a structural one, and the temperature sensitivity, the ability to reassemble the wild-type DNA binding surface at a low temperature, of the mutant protein. A total of 390 p53 mutants were rescued to varying degrees and thus were termed as type 1, type 2a, and type 2b mutations, depending on the degree to which they were rescued. The 33 type 1 mutations were rescued to amounts comparable to the wild type. In PDX mouse trials, ATO preferentially inhibited growth of tumors harboring type 1 and type 2a mutants. In an ATO clinical trial, we report the first-in-human mutant p53 reactivation in a patient harboring the type 1 V272M mutant. In 47 cell lines derived from 10 cancer types, ATO preferentially and effectively rescued type 1 and type 2a mutants, supporting the broad applicability of ATO in rescuing mutant p53. Our study provides the scientific and clinical communities with a resource of the druggabilities of numerous p53 mutations (www.rescuep53.net) and proposes a conceptual p53-targeting strategy based on individual mutant alleles rather than mutation type.


Assuntos
Neoplasias , Proteína Supressora de Tumor p53 , Humanos , Animais , Camundongos , Trióxido de Arsênio/metabolismo , Trióxido de Arsênio/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Mutação , Neoplasias/genética
9.
Sci Total Environ ; 880: 163251, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37023805

RESUMO

Dissolved organic matter (DOM) is a heterogeneous mixture of dissolved material found ubiquitously in aquatic systems and dissolved organic nitrogen is one of its most important components. We hypothesised nitrogen species and salinity intrusions affect the DOM changes. Here, using the nitrogen rich Minjiang River as an easily accessible natural laboratory 3 field surveys with 9 sampling sites (S1-S9) were conducted in November 2018, April and August 2019. The excitation emission matrices (EEMs) of DOM were explored with parallel factor (PARAFAC) and cosine-histogram similarity analysis. Four indices including fluorescence index (FI), biological index (BIX), humification index (HIX) and the fluorescent DOM (FDOM) were calculated and the impact of physicochemical properties was assessed. The results suggested that the highest salinities of 6.15, 2.98 and 10.10, during each campaign corresponded to DTN concentrations of 119.29-240.71, 149.12-262.42 and 88.27-155.29 µmol·L-1, respectively. PARAFAC analysis revealed the presence of tyrosine-like proteins (C1), tryptophan-like proteins or a combination of the peak N and tryptophan-like fluorophore (C2) and the humic-like material (C3). The EEMs in the upstream reach (i.e. S1-S3) were complex with larger spectra ranges, higher intensities and similar similarity. Subsequently, the fluorescence intensity of three components decreased significantly with low similarity of EEMs (i.e. S4-S7). At the downstream, the fluorescence levels dispersed significantly and no obvious peaks were seen except in August. In addition, FI and HIX increased, while BIX and FDOM decreased from upstream to downstream. The salinity positively correlated with FI and HIX, and negatively related to BIX and FDOM. Besides, the elevated DTN had a significant effect on the DOM fluorescence indices. Altogether, salinity intrusion and elevated nitrogen are relevant for the distribution of the DOM, which is helpful for the water management tracing the DOM source according to the on-line monitoring of salinity and nitrogen in estuaries.

10.
Chemosphere ; 321: 138139, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36791818

RESUMO

Emerging evidence indicated phthalate exposure might raise the risk of eczema in children. However, these findings were inconsistent. The relation between phthalate exposure and childhood eczema remained debated. Therefore, we performed this meta-analysis to assess their association. PubMed, Web of Science, and Embase were searched for eligible studies. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated for risk estimate. Thirty studies involving 12,615 participants were included in this meta-analysis. For prenatal phthalate exposure assessed with maternal samples, the pooled results showed gestational exposure to monobenzyl phthalate (MBzP) (OR: 1.17, 95% CI: 1.00-1.36), but not the other phthalates, was correlated with increased risk of eczema in children. For childhood exposure assessed using children's urine sample, our pooled results indicated that postnatal exposure to MBzP (OR: 1.10, 95% CI: 1.02-1.19), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (OR: 1.32, 95% CI: 1.08-1.61), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) (OR: 1.24, 95% CI: 1.06-1.44), and molar summation of di-2-ethylhexyl phthalate (DEHP) (OR: 1.23, 95% CI: 1.06-1.42) were associated with higher risk of eczema. While for studies using household dust to estimate environmental phthalate exposure and eczema risk, the pooled results showed no significant association. Subgroup analyses indicated study country, diagnostic mode, and children's age contributed to the heterogeneity. The results of our meta-analysis demonstrated that phthalate exposure during both prenatal and postnatal periods was associated with elevated risk of eczema in children. However, such association was not strong as the pooled ORs were relatively small. Further studies are warranted to verify these findings and explore the underlying mechanism.


Assuntos
Dietilexilftalato , Eczema , Poluentes Ambientais , Ácidos Ftálicos , Feminino , Gravidez , Humanos , Criança , Ácidos Ftálicos/análise , Exposição Ambiental/análise , Eczema/induzido quimicamente , Razão de Chances , Poluentes Ambientais/análise
11.
Sci Total Environ ; 866: 161438, 2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36623659

RESUMO

Identifying the mixing processes of waters and currents in tidal reach is an important aspect of environmental management to protect freshwater resources and prevent water pollution. In this study, three field investigations conducted in a typical tidal reach in August, November and the following April focused on two isotopes (δD and δ18O) and salinity. A salinity-isotope conservative mixing model was established to differentiate water flows of the important control interface (CI) from freshwater, transition zone and saltwater end-members. Results suggested that the average δD and δ18O values during the ebb and flood tides depleted from August to November, then enriched significantly in the following April and were even higher than those in August. The δD and δ18O values in the saltwater zone enriched markedly compared with those in freshwater zone and transition zone due to the stronger evaporation occurring in the saltwater zone. Based on the revised model, the average contributions of freshwater end-member, transition zone end-member and saltwater end-member in three months were, respectively, 51.50 %, 36.93 % and 11.57 %. However, the contributions of freshwater and transition zones in April end-member were equivalent (47.45 % vs 44.31 %). Meanwhile the largest contribution of saltwater end-member was 20.56 % and occurred in August. The proportions of three end-members that contributed to CI changed with different evaporation scenarios and moisture sources of precipitation. Our research provides important information that furthers our understanding of the isotopes and their applications to environmental management in estuarine regions.

12.
Transl Neurodegener ; 12(1): 1, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624510

RESUMO

BACKGROUND: Ribosomal protein S6 kinase 1 (S6K1) is a serine-threonine kinase that has two main isoforms: p70S6K (70-kDa isoform) and p85S6K (85-kDa isoform). p70S6K, with its upstream mammalian target of rapamycin (mTOR), has been shown to be involved in learning and memory and participate in the pathophysiology of Alzheimer's disease (AD). However, the function of p85S6K has long been neglected due to its high similarity to p70S6k. The role of p85S6K in learning and memory is still largely unknown. METHODS: We fractionated the postsynaptic densities to illustrate the differential distribution of p85S6K and p70S6K. Coimmunoprecipitation was performed to unveil interactions between p85S6K and the GluA1 subunit of AMPA receptor. The roles of p85S6K in synaptic targeting of GluA1 and learning and memory were evaluated by specific knockdown or overexpression of p85S6K followed by a broad range of methodologies including immunofluorescence, Western blot, in situ proximity ligation assay, morphological staining and behavioral examination. Further, the expression level of p85S6K was measured in brains from AD patients and AD model mice. RESULTS: p85S6K, but not p70S6K, was enriched in the postsynaptic densities. Moreover, knockdown of p85S6K resulted in defective spatial and recognition memory. In addition, p85S6K could interact with the GluA1 subunit of AMPA receptor through synapse-associated protein 97 and A-kinase anchoring protein 79/150. Mechanistic studies demonstrated that p85S6K could directly phosphorylate GluA1 at Ser845 and increase the amount of GluA1 in synapses, thus sustaining synaptic function and spine densities. Moreover, p85S6K was found to be specifically decreased in the synaptosomal compartment in the brains of AD patients and AD mice. Overexpression of p85S6K ameliorated the synaptic deficits and cognitive impairment in transgenic AD model mice. CONCLUSIONS: These results strongly imply a significant role for p85S6K in maintaining synaptic and cognitive function by interacting with GluA1. The findings provide an insight into the rational targeting of p85S6K as a therapeutic potential for AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Animais , Camundongos , Doença de Alzheimer/genética , Receptores de AMPA , Disfunção Cognitiva/genética , Cognição , Camundongos Transgênicos , Mamíferos
13.
J Colloid Interface Sci ; 632(Pt B): 299-310, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36435071

RESUMO

The widespread use of antibiotics, such as oxytetracycline (OTC) and levofloxacin (LEV), has led to dangerous levels of environmental contamination. In this study, functionalized iron/manganese nanoparticles (Fe/Mn NPs), which act as both adsorbent and Fenton catalyst, were green-synthesized using a reducing agent derived from a tea extract. The resulting pre-sorption/Fenton-like oxidation system effectively removed both OTC and LEV from the aqueous solution with adsorption capacities of Fe/Mn NPs for OTC and LEV of 58.8 and 192.3 mg·g-1, respectively. In addition, Fe/Mn NPs also showed high catalytic activity, oxidizing more than 99.9 % of both OTC and LEV, while sodium persulfate (PDS) removed only 26.6 and 29.0 % of OTC and LEV, respectively. Mechanisms of PDS activation typically involve either catalyst-initiated or mediated electron transfer reactions. Fe/Mn NPs through heterogeneous catalytic and metal leaching-induced homogeneous Fenton reactions, which generated various reactive oxygen species (ROS) including 1O2, ·OH, SO4-· and ·O2-. Characterization of Fe/Mn NPs before and after reaction, and the identification of specific OTC and LEV degradation products by LC-MS, helped to elucidate a potential degradation pathway, as well as the removal mechanism. Finally, the practicality of using this system for wastewater treatment was demonstrated using real wastewater samples indicating that the system has great potential for simultaneously degrading both OTC and LEV in contaminated wastewater.


Assuntos
Nanopartículas , Oxitetraciclina , Levofloxacino , Águas Residuárias , Ferro , Eletrólitos , Oxirredução
14.
EMBO Rep ; 23(6): e54147, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35373418

RESUMO

Developmental arsenic exposure has been associated with cognitive deficits in epidemiological studies, but the underlying mechanisms remain poorly understood. Here, we establish a mouse model of developmental arsenic exposure exhibiting deficits of recognition and spatial memory in the offspring. These deficits are associated with genome-wide DNA hypomethylation and abnormal expression of cognition-related genes in the hippocampus. Arsenic atoms directly bind to the cysteine-rich ADD domain of DNA methyltransferase 3A (DNMT3A), triggering ubiquitin- and proteasome-mediated degradation of DNMT3A in different cellular contexts. DNMT3A degradation leads to genome-wide DNA hypomethylation in mouse embryonic fibroblasts but not in non-embryonic cell lines. Treatment with metformin, a first-line antidiabetic agent reported to increase DNA methylation, ameliorates the behavioral deficits and normalizes the aberrant expression of cognition-related genes and DNA methylation in the hippocampus of arsenic-exposed offspring. Our study establishes a DNA hypomethylation effect of developmental arsenic exposure and proposes a potential treatment against cognitive deficits in the offspring of pregnant women in arsenic-contaminated areas.


Assuntos
Arsênio , Metilação de DNA , DNA Metiltransferase 3A , Animais , Arsênio/toxicidade , Cognição , Feminino , Fibroblastos/metabolismo , Humanos , Camundongos , Gravidez
15.
Cell Rep ; 39(2): 110622, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35417717

RESUMO

The tumor suppressor p53 is inactivated by over hundreds of heterogenous mutations in cancer. Here, we purposefully selected phenotypically reversible temperature-sensitive (TS) p53 mutations for pharmacological rescue with thermostability as the compound-screening readout. This rational screening identified antiparasitic drug potassium antimony tartrate (PAT) as an agent that can thermostabilize the representative TS mutant p53-V272M via noncovalent binding. PAT met the three basic criteria for a targeted drug: availability of a co-crystal structure, compatible structure-activity relationship, and intracellular target specificity, consequently exhibiting antitumor activity in a xenograft mouse model. At the antimony dose in clinical antiparasitic therapy, PAT effectively and specifically rescued p53-V272M in patient-derived primary leukemia cells in single-cell RNA sequencing. Further scanning of 815 frequent p53-missense mutations identified 65 potential PAT-treatable mutations, most of which were temperature sensitive. These results lay the groundwork for repurposing noncovalent antiparasitic antimonials for precisely treating cancers with the 65 p53 mutations.


Assuntos
Neoplasias , Proteína Supressora de Tumor p53 , Animais , Antimônio/metabolismo , Antimônio/farmacologia , Antimônio/uso terapêutico , Antiparasitários , Reposicionamento de Medicamentos , Humanos , Camundongos , Mutação/genética , Neoplasias/genética , Temperatura , Proteína Supressora de Tumor p53/metabolismo
16.
Diagn Cytopathol ; 50(6): 300-312, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35322590

RESUMO

PURPOSE: To compare and analyze the diagnostic efficacy of nuclear matrix protein 22 (NMP22) and urine cytology (UC) in the diagnosis of bladder cancer. METHODS: Search the Chinese and English studies on NMP22 and urinary cytology in the diagnosis of bladder tumors published between 1999 and June, and conduct quality evaluation, data extraction and analysis. RESULTS: A total of 397 related articles were retrieved, and 12 articles were finally included after screening, including 2456 subjects. The heterogeneity test shows that there is no discernible threshold effect. Perform meta-analysis according to the random effects model. The results showed that the total sensitivity of NMP22 and UC were 0.79 (95% CI [0.73, 0.84]) (CI: Confidence interval), 0.55 (95% CI [0.41, 0.69]), and the total specificity 0.59 (95% CI [0.46], respectively, 0.71), 0.91 (95% CI (0.81, 0.96]), +LR 1.9 (95% CI [1.4, 2.6]) (+LR: positive likelihood ration), 5.9 (95% CI [3.3, 10.6]), -LR 0.35 (-LR: negative likelihood ration), respectively (95% CI [0.27, 0.47]), 0.49 (95% CI [0.38, 0.64]), diagnostic odds ratios 5 (95% CI [3, 9]), 12 (95% CI [7, 21]). The area under the summary receiver operating characteristics curve (AUC) was 0.79 (95% CI [0.75, 0.82]) and 0.81 (95% CI [0.77, 0.84]), respectively. CONCLUSIONS: NMP22 has moderate diagnostic efficiency for bladder cancer. Its sensitivity is greater than UC, but its specificity is significantly lower than that of UC. At present, it cannot replace traditional cystoscopy and UC, but it can be combined to detect bladder tumors. It plays a major role in screening, postoperative monitoring and follow-up.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Biomarcadores Tumorais , Carcinoma de Células de Transição/diagnóstico , Feminino , Humanos , Masculino , Proteínas Nucleares , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia
17.
Ann Palliat Med ; 10(9): 9859-9869, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628912

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) causes joint pain and dysfunction that severely affects the patient's ability to walk. Arthroscopy combined with intraarticular injection of sodium hyaluronate can slow the development of knee osteoarthritis, but there is a lack of rigorous evidence-based medicine evaluation, and it has not been recognized by some scholars at home and abroad. This paper analyzed the clinical efficacy of arthroscopy combined with intraarticular injection of sodium hyaluronate in slowing knee osteoarthritis based on Lysholm score. METHODS: Randomized control trials of arthroscopy combined with intra-articular injection of sodium hyaluronate in the treatment of KOA on Chinese and English databases were retrieved using the following search terms: "knee osteoarthritis", "arthroscopic debridement of the joint", "articular cavity", and "sodium hyaluronate". The quality of the literature was evaluated using the Rev Man 5.3 software. RESULTS: Twelve literatures were included in the meta-analysis. Regarding Newcastle-Ottawa Scale (NOS) score, of the 12 literatures, 7 literatures (58.33%) scored 6-9 points, 3 literatures (25%) scored 3-5 points, and 2 literatures (16.67%) scored 0-2 points. With a random effects model used for analysis, the Lysholm score after 1 month of combined treatment was significantly higher than that before treatment [mean difference (MD) =30.65, 95% confidence interval (CI): 19.44, 41.86, P<0.01]. Further, after 3 months of combination treatment, the Lysholm score was significantly higher than that before treatment (MD =24.04, 95% CI: 13.75, 34.32, P<0.01), and the same trend was also observed after 6 months (MD =20.41, 95% CI: 14.43, 26.40, P<0.01) and after 12 months (MD =20.86, 95% CI: 8.99, 32.72, P<0.01) of combination treatment. Overall, the combined treatment achieved significantly better clinical therapeutic effects than the single treatments in the control group [odds ratio (OR) =7.51, 95% CI: 4.84, 11.65, P<0.01]. DISCUSSION: This meta-analysis has confirmed that arthroscopy combined with intra-articular injection of sodium hyaluronate demonstrates significant clinical therapeutic effects in the treatment of KOA. This combination treatment can significantly improve knee joint function, relieve clinical symptoms, and improve patients' quality of life.


Assuntos
Ácido Hialurônico , Osteoartrite do Joelho , Artroscopia , Humanos , Ácido Hialurônico/uso terapêutico , Injeções Intra-Articulares , Osteoartrite do Joelho/tratamento farmacológico , Qualidade de Vida
18.
Ann Transl Med ; 8(18): 1158, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33241007

RESUMO

BACKGROUND: To evaluate the role of high-resolution computed tomography (HRCT) in the diagnosis of 2019 novel coronavirus (2019-nCoV) pneumonia and to provide experience in the early detection and diagnosis of 2019-nCoV pneumonia. METHODS: Seventy-two patients confirmed to be infected with 2019-nCoV from multiple medical centers in western China were retrospectively analyzed, including epidemiologic characteristics, clinical manifestations, laboratory findings and HRCT chest features. RESULTS: All patients had lung parenchymal abnormalities on HRCT scans, which were mostly multifocal in both lungs and asymmetric in all patients, and were mostly in the peripheral or subpleural lung regions in 52 patients (72.22%), in the central lung regions in 16 patients (22.22%), and in both lungs with "white lung" manifestations in 4 patients (5.56%). Subpleural multifocal consolidation was a predominant abnormality in 38 patients (52.78%). Ground-glass opacity was seen in 34 patients (47.22%). Interlobular septal thickening was found in 18 patients, 8 of whom had only generally mild thickening with no zonal predominance. Reticulation was seen in 8 patients (11.11%), and was mild and randomly distributed. In addition, both lungs of 28 patients had 2 or 3 CT imaging features. Out of these 72 patients, 36 were diagnosed as early stage, 32 patients as progressive stage, and 4 patient as severe stage pneumonia. Moreover, the diagnostic accuracy of HRCT features combined with epidemiological history was not significantly different from the detection of viral nucleic acid (all P >0.05). CONCLUSIONS: The HRCT features of 2019-nCoV pneumonia are characteristic to a certain degree, which when combined with epidemiological history yield high clinical value in the early detection and diagnosis of 2019-nCoV pneumonia.

19.
Mol Nutr Food Res ; 64(14): e2000096, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32506806

RESUMO

SCOPE: The effect of α-mangostin (α-M), a polyphenolic xanthone isolated from mangostin, on lipopolysaccharide (LPS)-induced microglial activation and memory impairment is explored. The possible underlying mechanisms are also investigated. METHODS AND RESULTS: Cytokine production and activation of transforming growth factor activated kinase-1 (TAK1) and nuclear factor-κB (NF-κB) are detected by enzyme-linked immunosorbent assay (ELISA) or Western blot. Microglial migration and phagocytosis are evaluated with scratch wound-healing assay and phagocytosis of fluorescent latex beads, respectively. Learning and memory abilities of mice are evaluated with the Morris water maze test. The nanomolar (100-500 nm) α-M suppresses LPS-induced pro-inflammatory cytokine production and inducible nitric oxide synthase (iNOS) expression in microglia. It also inhibits LPS-induced microglial migration and phagocytosis. α-M rescues LPS-caused, microglia-mediated neuronal dendritic damage. Moreover, α-M represses LPS-induced toll-like receptor 4 (TLR4) expression and activation of TAK1 and NF-κB. In a mouse neuroinflammation model, α-M (50 mg kg-1 day-1 ) shows obvious anti-neuroinflammatory, neuroprotective, and memory-improving effects in vivo. CONCLUSION: α-M inhibits microglia-mediated neuroinflammation and prevents neurotoxicity and memory impairment from inflammatory damage. These results indicate that α-M has great potential to be used as a nutritional preventive strategy for neuroinflammation-related neurodegenerative disorders such as Alzheimer's disease.


Assuntos
Encefalite/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Microglia/efeitos dos fármacos , Xantonas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Citocinas/metabolismo , Dendritos/efeitos dos fármacos , Dendritos/patologia , Encefalite/metabolismo , Encefalite/patologia , Lipopolissacarídeos/toxicidade , MAP Quinase Quinase Quinases/metabolismo , Masculino , Transtornos da Memória/metabolismo , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , NF-kappa B/metabolismo , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Fagocitose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
20.
ACS Omega ; 5(24): 14575-14585, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32596595

RESUMO

H2S is a small molecule known to have multiple signaling roles in animals. Recently, evidence shows that H2S also has signaling functions in plants; however, the role of H2S in invasive plants is unknown. Spartina alterniflora is a typical invasive species growing along the beaches of southern China. A physiological comparison proves that S. alterniflora is highly tolerant to salinity stress compared with the native species Cyperus malaccensis. To decipher the mechanism that enables S. alterniflora to withstand salinity stress, a chemico-proteomics analysis was performed to examine the salt stress response of the two species; an inhibitor experiment was additionally designed to investigate H2S signaling on salinity tolerance in S. alterniflora. A total of 86 proteins belonging to nine categories were identified and differentially expressed in S. alterniflora exposed to salt stress. Moreover, the expression level of enzymes responsible for the H2S biosynthesis was markedly upregulated, indicating the potential role of H2S signaling in the plant's response to salt stress. The results suggested that salt triggered l-CD enzyme activity and induced the production of H2S, therefore upregulating expression of the antioxidants ascorbate peroxidase, superoxide dismutase, and S-nitrosoglutathione reductase, which mitigates damage from reactive nitrogen species. Additionally, H2S reduced the potassium efflux, thereby sustaining intracellular sodium/potassium ion homeostasis and enhancing S. alterniflora salt tolerance. These findings indicate that H2S plays an important role in the adaptation of S. alterniflora to saline environments, which provides greater insight into the function of H2S signaling in the adaptation of an invasive plant species.

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