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1.
Sci Rep ; 14(1): 13401, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862526

RESUMO

This study aimed to determine an immune-related RNA signature as a prognostic marker, in this study, we developed a risk score model for predicting the prognosis of osteosarcoma metastasis. We first downloaded the clinical information and expression data of osteosarcoma samples from the UCSC Xena and GEO databases, of which the former was the training set and the latter was the validation set. Immune infiltration was assessed using the ssGSEA and ESTIMATE algorithms, and the osteosarcoma samples were divided into the Immunity_L and Immunity_H groups. Then, eleven RNAs were identified as the optimal prognostic RNA signatures using LASSO Cox regression analysis for establishing a risk score (RS) model. Kaplan-Meier approach indicated the high-risk group exhibited a shorter survival. Furthermore, we analyzed the tumor metastasis, age, and RS model status were determined to be independent clinical prognostic factors using Cox regression analysis. Decision curve analysis (DCA) indicated that the prognostic factor + RS model had the best net benefit. Finally, nine tumor-infiltrating immune cells (TIICs) showed significant differences in abundance between high- and low-risk groups via CIBERSORT deconvolution algorithm. In conclusion, the immune-related eleven-RNA signature be could served as a potential prognostic biomarker for osteosarcoma metastasis.


Assuntos
Biomarcadores Tumorais , Neoplasias Ósseas , Osteossarcoma , Osteossarcoma/genética , Osteossarcoma/imunologia , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Humanos , Prognóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/patologia , Biomarcadores Tumorais/genética , Feminino , Masculino , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , Estimativa de Kaplan-Meier , Perfilação da Expressão Gênica , Transcriptoma , Modelos de Riscos Proporcionais , Fatores de Risco , Algoritmos
2.
Cell Rep Med ; 4(10): 101222, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37794586

RESUMO

Sporadic synchronous colorectal cancer (SCRC) refers to multiple primary CRC tumors detected simultaneously in an individual without predisposing hereditary conditions, which accounts for the majority of multiple CRCs while lacking a profound understanding of the genomic landscape and evolutionary dynamics to optimize its treatment. In this study, 103 primary tumor samples from 51 patients with SCRC undergo whole-exome sequencing. The germline and somatic mutations and evolutionary and clinical features are comprehensively investigated. Somatic genetic events are largely inconsistent between paired tumors. Compared with solitary CRC, SCRCs have higher prevalence of tumor mutation burden high (TMB-H; 33.3%) and microsatellite-instability high (MSI-H; 29.4%) and different mutation frequencies in oncogenic signaling pathways. Moreover, neutrally evolving SCRC tumors are associated with higher intratumoral heterogeneity and better prognosis. These findings unveil special molecular features, carcinogenesis, and prognosis of sporadic SCRC. Strategies for targeted therapy and immunotherapy should be optimized accordingly.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Instabilidade de Microssatélites , Prognóstico , Biomarcadores Tumorais/genética , Genômica
3.
Mar Pollut Bull ; 187: 114505, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36566512

RESUMO

Microplastics (MPs) are widely distributed in marine environments. The pollution characteristics and risk assessment of MPs in estuarine sediments are still insufficient. In this study, the MPs pollution characteristics in surface sediments of the Liao Estuary and Daliao Estuary were investigated. The characteristics of MPs in sediments were determined by stereo microscopy and micro-Fourier transform infrared spectroscopy. The results showed that the average MPs abundance ranged from 32.33 to 49.91 items·kg-1 d.w. The MPs were mainly composed of 500-2000 µm black and blue fibers. Five polymer types were identified, including rayon (RA) (87.46 %), polyethylene terephthalate (PET) (6.81 %), polyamide (PA) (2.94 %), polypropylene (PP) (2.17 %) and polyethylene (PE) (0.62 %). The pollution load index (PLI) risk assessment showed that all sampling sites were at Hazard Level I. Our results can provide useful information for assessing the environmental risks of MPs in coastal areas of China.


Assuntos
Microplásticos , Poluentes Químicos da Água , Plásticos/química , Baías/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental , China , Sedimentos Geológicos
4.
Front Plant Sci ; 13: 883140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35712579

RESUMO

Eudicots account for ~75% of living angiosperms, containing important food and energy crops. Recently, high-quality genome sequences of several eudicots including Aquilegia coerulea and Nelumbo nucifera have become available, providing an opportunity to investigate the early evolutionary characteristics of eudicots. We performed genomic hierarchical and event-related alignments to infer homology within and between representative species of eudicots. The results provide strong evidence for multiple independent polyploidization events during the early diversification of eudicots, three of which are likely to be allopolyploids: The core eudicot-common hexaploidy (ECH), Nelumbo-specific tetraploidy (NST), and Ranunculales-common tetraploidy (RCT). Using different genomes as references, we constructed genomic alignment to list the orthologous and paralogous genes produced by polyploidization and speciation. This could provide a fundamental framework for studying other eudicot genomes and gene(s) evolution. Further, we revealed significantly divergent evolutionary rates among these species. By performing evolutionary rate correction, we dated RCT to be ~118-134 million years ago (Mya), after Ranunculales diverged with core eudicots at ~123-139 Mya. Moreover, we characterized genomic fractionation resulting from gene loss and retention after polyploidizations. Notably, we revealed a high degree of divergence between subgenomes. In particular, synonymous nucleotide substitutions at synonymous sites (Ks) and phylogenomic analyses implied that A. coerulea might provide the subgenome(s) for the gamma-hexaploid hybridization.

5.
BMC Plant Biol ; 22(1): 298, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35710333

RESUMO

BACKGROUND: Gene conversion has an important effect on duplicate genes produced by polyploidization. Poplar (Populus trichocarpa) and willow (Salix brachista) are leading models and excellent green plants in the Salicaceae. Although much attention has been paid to the evolution of duplicated genes in poplar and willow, the role of conversion between duplicates generated from polyploidization remains poorly understood. RESULTS: Here, through genomic synteny analyses, we identified duplicate genes generated by the Salicaceae common tetraploidization (SCT) in the poplar and willow genomes. We estimated that at least 0.58% and 0.25% of poplar and willow duplicates were affected by whole-gene conversion after the poplar-willow divergence, with more (5.73% and 2.66%) affected by partial-gene conversion. Moreover, we found that the converted duplicated genes were unevenly distributed on each chromosome in the two genomes, and the well-preserved homoeologous chromosome regions may facilitate the conversion of duplicates. Notably, we found that conversion maintained the similarity of duplicates, likely contributing to the conservation of certain sequences, but is essentially accelerated the rate of evolution and increased species divergence. In addition, we found that converted duplicates tended to have more similar expression patterns than nonconverted duplicates. We found that genes associated with multigene families were preferentially converted. We also found that the genes encoding conserved structural domains associated with specific traits exhibited a high frequency of conversion. CONCLUSIONS: Extensive conversion between duplicate genes generated from the SCT contributes to the diversification of the family Salicaceae and has had long-lasting effects on those genes with important biological functions.


Assuntos
Populus , Salix , Evolução Molecular , Genes Duplicados/genética , Família Multigênica , Populus/genética , Salix/genética , Sintenia
6.
Nat Commun ; 13(1): 2342, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35487942

RESUMO

The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research.


Assuntos
Neoplasias Colorretais , Exoma , Instabilidade Cromossômica , Neoplasias Colorretais/genética , Exoma/genética , Genômica , Humanos , Cinesinas , Sequenciamento do Exoma/métodos
7.
Sci Total Environ ; 831: 154769, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35339544

RESUMO

Microbial colonization and biofilm formation associated with microplastics (MPs) have recently attracted wide attention. However, little is known about the effect of MP aging and different exposed habitats on biofilm formation and associated microbial community characteristics. To obtain a comprehensive understanding, virgin and aged polypropylene MPs were selected as attachment substrates and exposed to different aquatic habitats (marine, estuary, and river). The results showed that the aging process could destroy surface structure and increase oxygen-containing groups of MPs. The total biomass of the biofilms, attached-bacterial OTU numbers, and α diversities increased with exposure time. The biofilms biomass and α diversity of MPs in the river were significantly higher than those in the marine and estuary habitats, and temperature and salinity were primary factors affecting microbial colonization. Bacterial communities in MP-attached biofilms were significantly different from those in surrounding water. Microorganisms tend to adhere to aged MPs, and especially, genes related to human pathogens were significantly expressed on aged MPs, suggesting a potential ecological and health risk of aged MPs in aquatic ecosystems. Our results showed that aged MPs and different habitats have an important influence on microbial colonization, and the weathering process can accelerate biofilm formation on MPs.


Assuntos
Microplásticos , Poluentes Químicos da Água , Idoso , Envelhecimento , Bactérias , Biofilmes , Ecossistema , Humanos , Plásticos , Polipropilenos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
8.
Exp Cell Res ; 414(2): 113085, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35292240

RESUMO

BACKGROUND: The physical health and quality of life of the elderly are severely affected by osteoporosis (OP). METHODS: We explored the regulatory mechanism of ICA in vivo and in vitro by constructing OP rats and inducing osteogenic differentiation of BMSCs. First, we determined the expression of miR-335-5p in bone tissues of OP patients, bone tissues of OP rats, and osteogenic BMSCs by RT-qPCR. Alizarin red staining was employed to detect the formation of calcium nodules in the cells. MTT was used to detect cell viability. Finally, we detected the bone tissue changes in OP rats by overexpression of miR-335-5p or oral ICA. RESULTS: miR-335-5p was lowly expressed in bone tissues of OP patients and OP rats. ICA treatment reversed the inhibitory effect of miR-335-5p inhibitor on BMSCs matrix mineralization. Moreover, PTEN was verified to be a downstream effector of miR-335-5p. During ICA induction, overexpression of PTEN reversed the promotive effect of miR-335-5p mimics on the osteogenic differentiation of BMSCs. In vivo experiments also found that overexpression of miR-335-5p or ICA treatment improved the pathogenesis of OP in rats. CONCLUSION: ICA improved OP by up-regulating miR-335-5p to inhibit PTEN, thereby providing a new strategy for the prevention and treatment of OP.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Osteoporose , Idoso , Animais , Células da Medula Óssea/metabolismo , Diferenciação Celular , Células Cultivadas , Flavonoides , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Osteogênese/genética , Osteoporose/tratamento farmacológico , Osteoporose/genética , Osteoporose/metabolismo , Qualidade de Vida , Ratos
9.
Sci Total Environ ; 807(Pt 3): 151049, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34673075

RESUMO

Microplastics (MPs) are widely detected in many marine fishes. Fish meal contaminated by MP may constitute a potential threat to aquaculture animals. This study analyzed the characteristics of MP in fish meals from ten major fish meal-producing countries around the world. Microplastics were isolated from fish meal, examined under a microscope and identified using Fourier transform infrared microspectroscopy (µ-FT-IR). The results showed that MP pollution was widely detected in fish meal samples from ten countries. The average MP abundance of fish meals was 5.5 ± 1.6 items/g, with higher levels in China, Peru and Myanmar, which might be related to the high pollution level in fish and their habitats. In isolated MPs, fibers were the main shape type, and the most common size was 500-1000 µm. A total of 6 polymers were identified, with cellophane (CP), polypropylene (PP) and polyethylene teraphalate (PET) being the most common types. The total amount of MP ingestion from fish meals by different cultured animals was also estimated, with Atlantic salmon Salmon salar ingesting the largest number of MPs (9361 items), and red swamp crayfish Procambarus clarkii ingesting the smallest number of MPs (19 items). Thus, fish meal constitutes an important exposure route of MPs for aquaculture animals. The results of this study will provide a basis to assess the potential health risks of MPs in fish meals around the world.


Assuntos
Microplásticos , Plásticos , Animais , Aquicultura , Peixes , Refeições , Polietileno , Espectroscopia de Infravermelho com Transformada de Fourier
10.
Genes (Basel) ; 12(12)2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34946893

RESUMO

The peanut (Arachis hypogaea L.) is the leading oil and food crop among the legume family. Extensive duplicate gene pairs generated from recursive polyploidizations with high sequence similarity could result from gene conversion, caused by illegitimate DNA recombination. Here, through synteny-based comparisons of two diploid and three tetraploid peanut genomes, we identified the duplicated genes generated from legume common tetraploidy (LCT) and peanut recent allo-tetraploidy (PRT) within genomes. In each peanut genome (or subgenomes), we inferred that 6.8-13.1% of LCT-related and 11.3-16.5% of PRT-related duplicates were affected by gene conversion, in which the LCT-related duplicates were the most affected by partial gene conversion, whereas the PRT-related duplicates were the most affected by whole gene conversion. Notably, we observed the conversion between duplicates as the long-lasting contribution of polyploidizations accelerated the divergence of different Arachis genomes. Moreover, we found that the converted duplicates are unevenly distributed across the chromosomes and are more often near the ends of the chromosomes in each genome. We also confirmed that well-preserved homoeologous chromosome regions may facilitate duplicates' conversion. In addition, we found that these biological functions contain a higher number of preferentially converted genes, such as catalytic activity-related genes. We identified specific domains that are involved in converted genes, implying that conversions are associated with important traits of peanut growth and development.


Assuntos
Arachis/genética , Evolução Molecular , Genes Duplicados , Genoma de Planta , Poliploidia , Recombinação Genética , Arachis/classificação , Arachis/metabolismo , Biologia Computacional , Bases de Dados Genéticas , Análise de Sequência de DNA/métodos
12.
BMC Genomics ; 22(1): 460, 2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34147070

RESUMO

BACKGROUND: Duplicated gene pairs produced by ancient polyploidy maintain high sequence similarity over a long period of time and may result from illegitimate recombination between homeologous chromosomes. The genomes of Asian cultivated rice Oryza sativa ssp. indica (XI) and Oryza sativa ssp. japonica (GJ) have recently been updated, providing new opportunities for investigating ongoing gene conversion events and their impact on genome evolution. RESULTS: Using comparative genomics and phylogenetic analyses, we evaluated gene conversion rates between duplicated genes produced by polyploidization 100 million years ago (mya) in GJ and XI. At least 5.19-5.77% of genes duplicated across the three rice genomes were affected by whole-gene conversion after the divergence of GJ and XI at ~ 0.4 mya, with more (7.77-9.53%) showing conversion of only portions of genes. Independently converted duplicates surviving in the genomes of different subspecies often use the same donor genes. The ongoing gene conversion frequency was higher near chromosome termini, with a single pair of homoeologous chromosomes, 11 and 12, in each rice genome being most affected. Notably, ongoing gene conversion has maintained similarity between very ancient duplicates, provided opportunities for further gene conversion, and accelerated rice divergence. Chromosome rearrangements after polyploidization are associated with ongoing gene conversion events, and they directly restrict recombination and inhibit duplicated gene conversion between homeologous regions. Furthermore, we found that the converted genes tended to have more similar expression patterns than nonconverted duplicates. Gene conversion affects biological functions associated with multiple genes, such as catalytic activity, implying opportunities for interaction among members of large gene families, such as NBS-LRR disease-resistance genes, contributing to the occurrence of the gene conversion. CONCLUSION: Duplicated genes in rice subspecies generated by grass polyploidization ~ 100 mya remain affected by gene conversion at high frequency, with important implications for the divergence of rice subspecies.


Assuntos
Oryza , Idoso de 80 Anos ou mais , Evolução Molecular , Duplicação Gênica , Genes Duplicados , Genoma de Planta , Humanos , Oryza/genética , Filogenia
13.
Sci Total Environ ; 770: 145303, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33515883

RESUMO

At present, microplastics (MPs) have gradually become a hot issue in marine environmental pollution and may pose a potential threat to marine ecosystems. Since MPs are not easily biodegradable, they can provide the attachment substrates for various organisms, which will affect their floating and transport, and may also lead to the invasion of harmful microorganisms. In this study, polypropylene, polyethylene, polylactic acid pellets, and glass particles were exposed for 6 weeks in different seasons at three stations in the Yellow Sea, China. The results showed that the total amounts of biofilms significantly varied among seasons and functional zones and that the temperature of seawater was the main influencing factor. A variety of biological communities (especially diatoms and bacteria) and extracellular polymeric substances were observed on the MP surfaces using scanning electron microscopy and confocal laser scanning microscopy. Sequencing analysis indicated that the structure and composition of microbial communities on MPs mainly varied with seasons and locations. In addition, most of the microorganisms were generally attached to the surface and were not any specific selection of plastic by different chemical compositions. However, the bacteria inhabiting microplastics harbored distinct metabolisms. Our results suggest that low-density MPs may settle quickly in summer in some eutrophic areas.


Assuntos
Microplásticos , Poluentes Químicos da Água , Biofilmes , China , Ecossistema , Monitoramento Ambiental , Plásticos , Estações do Ano , Poluentes Químicos da Água/análise
14.
Chemosphere ; 263: 127962, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32841876

RESUMO

Microplastic (MP) pollution has become an emerging global concern in marine environments, but research on the uptake of MPs by commercial marine fish is relatively sparse. In this study, 29 commercial fish species (n = 584) with different feeding habits and trophic levels were collected from 8 sites along the Bohai Sea for MP uptake analysis. Approximately 85.4% of the total fish among all species ingested MPs, and there was an average abundance of 2.14 items/individual or 0.043 items/g of wet weight. Compared with other studies, MP pollution in fishes from the Bohai Sea was relatively moderate. The MPs were predominantly fibrous in shape and were cellophane, polyethylene terephthalate (PET) and polypropylene (PP) in polymer composition. The highest abundance and polymer composition of MPs was observed in benthivores, suggesting that they might ingest these MPs from their food. The small fish Konosirus punctatus, which had a high level of MPs, may increase the risk of human exposure to the MPs when it is dried and consumed. Moreover, the spatial variation of MPs was determined in terms of abundance, shape composition, and major polymer types, but there was no marked relationship between MP abundance and the trophic levels of fish. Overall, this study provides a basis for the ecological risk assessment of MPs in fish and for a health risk assessment for human beings.


Assuntos
Monitoramento Ambiental , Peixes/metabolismo , Microplásticos/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , China , Poluição Ambiental/análise , Humanos , Plásticos/análise
15.
Am J Cancer Res ; 10(9): 3037-3046, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042632

RESUMO

Gastric cancer (GC) is the second most common cancer in China. The ToGA study showed that trastuzumab in combination with fluoropyrimidine plus cisplatin prolonged overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced GC (AGC). However, some patients may not be able to receive this regimen. We conducted a clinical study to evaluate the efficacy and safety of trastuzumab in combination with docetaxel+capecitabine (DX) in patients with HER2-positive AGC. This phase II, multi-center, open-label, single arm study enrolled patients with HER2-positive AGC who had not received prior treatment for metastatic disease. Patients were treated with a regimen of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg, day 1), capecitabine (1000 mg/m2 twice daily, days 1-14) and docetaxel (60 mg/m2, day 1 for 6 cycles) every 3 weeks. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), OS and safety profiles. Sixty-seven patients with AGC were enrolled from 14 centers. 64 were included in the full analysis set (FAS). The median PFS was 8.1 months (95% confidence interval [CI]: 5.6-12.8) and the median OS was 20.9 months (95% CI: 15.1-33.0). Response was evaluated in 59 patients. The ORR was 67.8%. The most common adverse events of Grade ≥3 were neutropenia, leukopenia, hand-foot syndrome, febrile neutropenia and anemia. We concluded that combination treatment with trastuzumab and DX was well-tolerated and highly effective in patients with HER2-positive AGC, and may offer an alternative to current treatments.

16.
Cancer Commun (Lond) ; 40(11): 620-632, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32914570

RESUMO

BACKGROUND: Inherited susceptibility accounts for nearly one-third of colorectal cancer (CRC) predispositions and has an 80%-100% lifetime risk of this disease. However, there are few data about germline mutations of hereditary CRC-related genes in Chinese patients with CRC. This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC, differences between Chinese and Western patients, and the phenotype-genotype correlation. METHODS: We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing. A series of bioinformatic analyses, as well as statistical comparisons, were performed. RESULTS: We found that 77 patients (14.6%) harbored functional variants of the 12 genes. The mutation frequencies of the top 5 mutated genes were 6.5% for MutL homolog 1 (MLH1), 5.1% for MutS homolog 2 (MSH2), 1.0% for MSH6, 0.8% for PMS1 homolog 2 (PMS2), and 0.8% for APC regulator of the WNT signaling pathway (APC). Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair (MMR) genes as compared with those in Western populations. Mutations in MLH1, MSH2, and MSH6 were found to be mutually exclusive. Patients with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer (MLH1: 20.6% vs. 8.7%; MSH2: 25.9% vs. 8.6%) and family history of cancer than those without these mutations (MLH1: 73.5% vs. 48.4%; MSH2: 70.4% vs. 48.9%), and the lesions were more prone to occur on the right side of the colon than on the left side (MLH1: 73.5% vs. 29.3%; MSH2: 56.0% vs. 31.0%). The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations (70.6% vs. 50.7%), and the rate of polyps was higher in patients with APC mutations than in those with wild-type APC (75.0% vs. 17.4%). CONCLUSION: These results provide a full-scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi-gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.


Assuntos
Neoplasias Colorretais , Mutação em Linhagem Germinativa , Idoso , China , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Feminino , Células Germinativas , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Estudos Retrospectivos
17.
Environ Pollut ; 263(Pt A): 114428, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32229373

RESUMO

Research on microplastic (MP) pollution in the marine environment has received widespread attention in recent years. To assess the degree of MP contamination in the intertidal zone of China, the abundance, shape, particle size and composition of MPs in sediment were investigated in this study. Sediment samples were collected from 13 stations along the coast of China. The density separation method was employed to isolate MPs from sediment and the polymer types of the MPs were determined by Fourier transform infrared microspectroscopy. Our study demonstrated that MP pollution was widespread in the 13 intertidal stations. The average abundance of MPs was 309 ± 81 items/kg dry weight. Fiber accounted for 71.5% of the isolated MPs, and the particles of less than 500 µm accounted for the highest proportion (35.0%). A total of 12 polymers were identified; the main types were rayon (RY), polypropylene (PP), polyethylene terephthalate (PET) and polyethylene (PE). The shape and chemical composition of the MPs from the intertidal sediments of South and North China were different. In South China, MP fragments were more extensive, and PP was a more important component. In contrast, the intertidal sediments of North China contained more MP fibers with the majority being RY, indicating that the major source of MPs in the intertidal zone of North China may be domestic sewage. Additionally, the abundance of MPs in the intertidal sediments of the Pearl River and Jiulong River estuaries was higher than at other sites. A Spearman's correlation analysis showed that there was no correlation between MP abundance and sediment grain size or organic matter content. Our study highlights the ubiquitous distribution of MPs in the sediment along the coast of China and provides valuable information for risk assessment and source control of MP pollution in China's intertidal zone.


Assuntos
Plásticos , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental , Sedimentos Geológicos , Microplásticos
18.
PeerJ ; 7: e6639, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31106043

RESUMO

BACKGROUND: Hydra actinoporin like toxin -1 (HALT-1), is a small 18.5 kDa pore forming toxin derived from Hydra magnipapillata which has been shown to elicit strong haemolytic and cytolytic activity when in contact with cell membranes. Due to its cytotoxic potency, HALT-1 was further investigated for its potential as a toxin moiety candidate in immunotoxin developmental efforts, ideally as a form of targeted therapy against cancer. METHODS: In this study, wtHALT-1 (wild type) and its Y110A mutated binding domain counterpart (mHALT-1) were produced and evaluated for their cytotoxic and apoptotic effects on various cancer cell lines. A total of seven different tumour and non-tumour cell lines including HeLa, HepG2, SW-620, MCF-7, CCD841CoN, NHDF and HCT116 were used. Immunofluorescence assays were used to observe membrane binding and localization changes between both HALT-1 recombinant proteins based on 6xHis-tag detection. RESULT: Based on MTT data, mHALT-1 demonstrated a significant reduction of 82% ±  12.21% in cytotoxic activity across all cell lines after the membrane recognition domain had been mutated in comparison to the wtHALT-1. Annexin V FITC/PI assay data also indicated that HeLa, HepG2 and MCF-7 demonstrated an apoptosis-mediated cell death after being treated with wtHALT-1. Additionally, a notable difference between wtHALT-1 and mHALT-1 binding affinity was clearly observed where emission of green fluorescence along the cell membrane was observed only in wtHALT-1 treated cells. DISCUSSION: These results suggest that mHALT-1 (Y110A) can be potentially developed as a toxin-moiety candidate for the development of future immunotoxins against various human cell-based diseases.

19.
Clin Rheumatol ; 38(1): 107-115, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30123930

RESUMO

To estimate the mortality and describe the causes of death in a large multicenter cohort of hospitalized patients with SLE in China. This was a retrospective study of a nationwide SLE cohort (10 centers, 29,510 hospitalized patients) from 2005 to 2014 in China. Standardized mortality ratios (SMRs) were calculated for all death and were stratified by sex and age. Chi-square test was used to determine whether the major causes of death vary in age, sex, duration of SLE, disease activity, or medications. Comparison between dead patients and survival controls was used to identify the risk factors for mortality. Logistic regression analysis was used to evaluate the risk factors for mortality. A total of 360 patients died during the study period, accounting for 1.22%. The overall SMR was 2.13 (95% CI 1.96, 2.30), with a particularly high SMR seen in subgroups characterized by younger age. Infection (65.8%) was the most common cause of death, followed by lupus nephritis (48.6%), hematological abnormality (18.1%), neuropsychiatric lupus/NPSLE (15.8%), and interstitial pneumonia (13.1%). Cardiovascular disease and malignancy contributed little to the causes of death. Infection, in particular severe pulmonary infection, emerged as the foremost risk factor for mortality, followed by lupus encephalopathy. However, lupus nephritis and hematological abnormalities occurred more frequently in survival patients. SLE patients at a younger age of diagnosis have a poorer prognosis. Infection dominated the causes of death in recent China. Ethnicity and medications might account for the differences in causes of death compared with western populations.


Assuntos
Causas de Morte , Lúpus Eritematoso Sistêmico/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/complicações , Criança , China/epidemiologia , Feminino , Humanos , Infecções/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Adulto Jovem
20.
BMC Immunol ; 18(1): 32, 2017 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-28645246

RESUMO

BACKGROUND: The monoclonal gammopathies are a group of plasma-cell proliferative disorders characterized by the secretion of monoclonal immunoglobulin (M protein or paraprotein). Some rare cases have revealed the specific affinity of paraprotein as autoantibody. Here we report a patient with monoclonal gammopathy of undetermined significance (MGUS) accompanied by a remarkable increase of anticardiolipin antibody (aCL) and an extensively decreased coagulation factor activity, however, without any clinical signs of antiphospholipid syndrome (APS) and bleeding. RESULTS: Our further investigation indicated that IgMκ paraprotein of this patient possessed an antibody activity against phospholipids so as to bind to cardiolipin and interfere with coagulation assay in vitro. CONCLUSIONS: This case might be indicative that an abnormality of coagulation tests, disturbed by IgMκ paraprotein, does not predict a risk of bleeding in this patient.


Assuntos
Autoanticorpos/metabolismo , Testes de Coagulação Sanguínea/métodos , Cardiolipinas/metabolismo , Erros de Diagnóstico/prevenção & controle , Imunoglobulina M/metabolismo , Cadeias kappa de Imunoglobulina/metabolismo , Paraproteinemias/diagnóstico , Coagulação Sanguínea , Testes de Coagulação Sanguínea/normas , Humanos , Imunoglobulina M/genética , Cadeias kappa de Imunoglobulina/genética , Masculino , Pessoa de Meia-Idade , Paraproteinemias/sangue , Ligação Proteica
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