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1.
J Proteome Res ; 23(6): 2028-2040, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38700954

RESUMO

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy that usually occurs among the nose and throat. Due to mild initial symptoms, most patients are diagnosed in the late stage, and the recurrence rate of tumors is high, resulting in many deaths every year. Traditional radiotherapy and chemotherapy are prone to causing drug resistance and significant side effects. Therefore, searching for new bioactive drugs including anticancer peptides is necessary and urgent. LVTX-8 is a peptide toxin synthesized from the cDNA library of the spider Lycosa vittata, which is consisting of 25 amino acids. In this study, a series of in vitro cell experiments such as cell toxicity, colony formation, and cell migration assays were performed to exam the anticancer activity of LVTX-8 in NPC cells (5-8F and CNE-2). The results suggested that LVTX-8 significantly inhibited cell proliferation and migration of NPC cells. To find the potential molecular targets for the anticancer capability of LVTX-8, high-throughput proteomic and bioinformatics analysis were conducted on NPC cells. The results identified EXOSC1 as a potential target protein with significantly differential expression levels under LVTX-8+/LVTX-8- conditions. The results in this research indicate that spider peptide toxin LVTX-8 exhibits significant anticancer activity in NPC, and EXOSC1 may serve as a target protein for its anticancer activity. These findings provide a reference for the development of new therapeutic drugs for NPC and offer new ideas for the discovery of biomarkers related to NPC diagnosis. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org) via the iProX partner repository with the data set identifier PXD050542.


Assuntos
Antineoplásicos , Movimento Celular , Proliferação de Células , Complexo Multienzimático de Ribonucleases do Exossomo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteômica , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Complexo Multienzimático de Ribonucleases do Exossomo/efeitos dos fármacos , Complexo Multienzimático de Ribonucleases do Exossomo/metabolismo , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Peptídeos/farmacologia , Peptídeos/química , Proteômica/métodos , Proteínas de Ligação a RNA/efeitos dos fármacos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Venenos de Aranha/farmacologia , Venenos de Aranha/química
2.
Biochem Biophys Res Commun ; 739: 150598, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39213754

RESUMO

Colorectal cancer is globally ranked as the third most common malignant tumor. Its development involves a complex biological process driven by various genetic and epigenetic alterations. To elucidate the biological significance of the extensive omics data, we conducted comparative multi-omics studies on colorectal cancer patients at different clinical stages. Bioinformatics methods were applied to analyze multi-omics datasets and explore the molecular landscape. Drug prediction and molecular docking also were conducted to assess potential therapeutic interventions. In vitro experiments were used to validate the inhibitory effect on the migration and proliferation of cell lines. The results indicate up-regulated proteins involved in immune-inflammatory related pathways, while biomarkers related to muscular contraction and cell adhesion are significantly down-regulated. Drug prediction, coupled with in vitro experiments, suggests that AZ-628 may act as a potential drug to inhibit the proliferation and migration of CRC cell lines HCT-116 and HT-29 by regulating the aforementioned key biological pathways or proteins. Complementing these findings, metabolomics analysis unveiled a down-regulation of key carbon metabolism pathways, alongside an up-regulation in amino acid metabolism, particularly proline metabolism. This metabolic shift may reflect an adaptive response in cancer cells, favoring specific amino acids to support their growth. Together, these integrated results provide valuable insights into the intricate landscape of tumor development, highlighting the crossroads of immune regulation, cellular structure, and metabolic reprogramming in the tumorigenic process and providing valuable insights into cancer pathology.

3.
Am J Gastroenterol ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382852

RESUMO

INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.

4.
Virol J ; 21(1): 201, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192225

RESUMO

BACKGROUND: The COVID-19 pandemic has underscored the critical role of sequencing technology in disease control and outbreak response. However, resource limitations and challenging environments often impede such efforts in low and middle-income countries. This study aimed to investigate the spectrum of viral co-infections, particularly with human viral pathogens, in SARS-CoV-2 positive individuals in Sierra Leone using metagenomic sequencing, evaluating the feasibility of utilizing this technology for epidemiological and evolutionary surveillance of pathogens related to public health in low-income environments. METHODS: We retrospectively collected and analyzed 98 nasopharyngeal swab specimens from SARS-CoV-2 positive individuals in Sierra Leone. Samples were pre-processed locally and transferred to China via FTA cards for metagenomic sequencing, which was performed using the Novaseq platform. The study focused on the identification of nasopharyngeal viruses co-infecting with SARS-CoV-2, with a deeper analysis of significant human viral pathogens such as HPV. RESULTS: The study identified 22 viral taxa from 20 families, including 4 human viruses. Notably, 19.4% of samples showed HPV co-infection with 34 distinct types, predominantly beta and gamma HPVs. Multiple HPV types were found in individual samples, indicating a high complexity of viral co-infections. CONCLUSIONS: The identification of a wide range of co-infecting viruses, particularly multiple HPV genotypes, highlights the complexity of viral interactions and their potential implications for public health. These findings enhance our understanding of viral co-infections and provide valuable insights for public health interventions in Sierra Leone. Further research is needed to explore the clinical significance of these findings and their impact on disease outcomes.


Assuntos
COVID-19 , Coinfecção , Infecções por Papillomavirus , SARS-CoV-2 , Humanos , Serra Leoa/epidemiologia , Estudos Retrospectivos , COVID-19/virologia , COVID-19/epidemiologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/classificação , Coinfecção/virologia , Coinfecção/epidemiologia , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Nasofaringe/virologia , Adolescente , Metagenômica , Filogenia , Papillomaviridae/genética , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Idoso , Criança
5.
Lipids Health Dis ; 23(1): 143, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760661

RESUMO

BACKGROUND: Lipid accumulation product (LAP) is an accessible and relatively comprehensive assessment of obesity that represents both anatomical and physiological lipid accumulation. Obesity and psoriasis are potentially related, according to previous research. Investigating the relationship between adult psoriasis and the LAP index was the goal of this study. METHODS: This is a cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2009-2014. The association between LAP and psoriasis was examined using multivariate logistic regression and smoothed curve fitting. To verify whether this relationship was stable across populations, subgroup analyses and interaction tests were performed. RESULTS: The LAP index showed a positive correlation with psoriasis in 9,781 adult participants who were 20 years of age or older. A 27% elevated probability of psoriasis was linked to every unit increase in ln LAP in the fully adjusted model (Model 3: OR 1.27, 95% CI 1.06-1.52). In comparison with participants in the lowest ln LAP quartile, those in the highest quartile had an 83% greater likelihood of psoriasis (Model 3: OR 1.83, 95% CI 1.08-3.11). This positive correlation was more pronounced for young males, participants who had never smoked, non-drinkers, participants who exercised little, as well as non-hypertensive and non-diabetic participants. CONCLUSIONS: This study found that the LAP index and adult psoriasis were positively correlated, especially in young males without comorbidities. Therefore, it is proposed that LAP may serve as a biomarker for early diagnosis of psoriasis and tracking the effectiveness of treatment.


Assuntos
Produto da Acumulação Lipídica , Inquéritos Nutricionais , Psoríase , Humanos , Psoríase/epidemiologia , Psoríase/metabolismo , Masculino , Adulto , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Obesidade/epidemiologia , Adulto Jovem , Fatores de Risco , Modelos Logísticos , Índice de Massa Corporal
6.
Crit Rev Biotechnol ; 43(3): 415-432, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35156471

RESUMO

While the research field and industrial market of in vitro diagnosis (IVD) thrived during and post the COVID-19 pandemic, the development of isothermal nucleic acid amplification test (INAAT) based rapid diagnosis was engendered in a global wised large measure as a problem-solving exercise. This review systematically analyzed the recent advances of INAAT strategies with practical case for the real-world scenario virus detection applications. With the qualities that make INAAT systems useful for making diagnosis relevant decisions, the key performance indicators and the cost-effectiveness of enzyme-assisted methods and enzyme-free methods were compared. The modularity of nucleic acid amplification reactions that can lead to thresholding signal amplifications using INAAT reagents and their methodology design were examined, alongside the potential application with rapid test platform/device integration. Given that clinical practitioners are, by and large, unaware of many the isothermal nucleic acid test advances. This review could bridge the arcane research field of different INAAT systems and signal output modalities with end-users in clinic when choosing suitable test kits and/or methods for rapid virus detection.


Assuntos
COVID-19 , Ácidos Nucleicos , Vírus , Humanos , Pandemias , Técnicas de Amplificação de Ácido Nucleico/métodos , Tecnologia
7.
Proteome Sci ; 21(1): 6, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37101287

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy cancer among the malignancies of thyroid. Despite of wide usages of proteomics in PTC, the profile of acetylated proteins in PTC remains unsettled, which is helpful for understanding the carcinogenesis mechanism and identifying useful biomarkers for PTC. METHODS: The surgically removed specimens of cancer tissues (Ca-T) and adjacent normal tissues (Ca-N) from 10 female patients pathological diagnosed as PTC (TNM stage III) were enrolled in the study. After preparing the pooled extracts of the whole proteins and the acetylated proteins from 10 cases, TMT labeling and LC/MS/MS methods were applied to the assays of global proteomics and acetylated proteomics separately. Bioinformatics analysis, including KEGG, gene ontology (GO) and hierarchical clustering were performed. Some differentially expressed proteins (DEPs) and differentially expressed acetylated proteins (DEAPs) were validated by individual Western blots. RESULTS: Controlled with the normal tissues adjacent to the lesions, 147 out of 1923 identified proteins in tumor tissues were considered as DEPs in global proteomics, including 78 up-regulated and 69 down-regulated ones, while 57 out of 311 identified acetylated proteins in tumor tissues were DEAPs in acetylated proteomics, including 32 up-regulated and 25 down-regulated, respectively. The top 3 up- and down-regulated DEPs were fibronectin 1, KRT1B protein and chitinase-3-like protein 1, as well as keratin, type I cytoskeletal 16, A-gamma globin Osilo variant and Huntingtin interacting protein-1. The top 3 up- and down-regulated DEAPs were ribosomal protein L18a-like protein, alpha-1-acid glycoprotein 2 and eukaryotic peptide chain release factor GTP-binding subunit ERF3A, as well as trefoil factor 3, thyroglobulin and histone H2B. Functional GO annotation and KEGG pathway analysis based on the DEPs and DEAPs showed completely different changing pictures. Contrary to the top 10 up- and -down regulated DEPs, most of which were addressed in PTC and other types of carcinomas, changes of the majority DEAPs were not mentioned in the literatures. CONCLUSIONS: Taken the profiling of the global and acetylated proteomics together will provide more broad view of protein alterations on the carcinogenesis and new direction for selecting biomarker for diagnosis of PTC.

8.
Arch Virol ; 168(11): 270, 2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37805966

RESUMO

Exosomes are double-layered vesicle bodies secreted by cells, in which microRNAs (miRNAs) play an important role. In a previous study, we found that treatment of the prion-infected cell line SMB-S15 with resveratrol can effectively inhibit the propagation of PrPSc in vitro and eliminate its infectivity in vivo. In this study, the global expression profiles of miRNAs in extracellular exosomes during resveratrol clearance of PrPSc in SMB-S15 cells were analyzed. Extracted exosomal miRNAs from the prion-infected cell line SMB-S15 (S15) and its normal partner cell line SMB-PS (PS) as well as SMB-S15 cells exposed to resveratrol for 4 days (RES4) and 8 days (RES8) were subjected into deep sequencing. Similarities and differences in the levels of differentially expressed miRNAs as well as the signaling pathways that are potentially involved were comparatively analyzed. The possible influences on the expression of genes affected by changes in exosomal miRNAs in the context of the prion pathway were further analyzed. These alterations in exosomal miRNA levels may help us to understand the functional transmission of intercellular messages and the pathogenesis of prion biology and prion disease.


Assuntos
Exossomos , MicroRNAs , Doenças Priônicas , Príons , Humanos , Resveratrol/farmacologia , Exossomos/metabolismo , Doenças Priônicas/patologia , MicroRNAs/genética
9.
Brain ; 145(2): 700-712, 2022 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-35288744

RESUMO

Genetic prion diseases are a rare and diverse group of fatal neurodegenerative disorders caused by pathogenic sequence variations in the prion protein gene, PRNP. Data on CSF biomarkers in patients with genetic prion diseases are limited and conflicting results have been reported for unclear reasons. Here, we aimed to analyse the diagnostic accuracy of CSF biomarkers currently used in prion clinical diagnosis in 302 symptomatic genetic prion disease cases from 11 prion diagnostic centres, encompassing a total of 36 different pathogenic sequence variations within the open reading frame of PRNP. CSF samples were assessed for the surrogate markers of neurodegeneration, 14-3-3 protein (14-3-3), total-tau protein (t-tau) and α-synuclein and for prion seeding activity through the real-time quaking-induced conversion assay. Biomarker results were compared with those obtained in healthy and neurological controls. For the most prevalent PRNP pathogenic sequence variations, biomarker accuracy and associations between biomarkers, demographic and genetic determinants were assessed. Additionally, the prognostic value of biomarkers for predicting total disease duration from symptom onset to death was investigated. High sensitivity of the four biomarkers was detected for genetic Creutzfeldt-Jakob disease associated with the E200K and V210I mutations, but low sensitivity was observed for mutations associated with Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. All biomarkers showed good to excellent specificity using the standard cut-offs often used for sporadic Creutzfeldt-Jakob disease. In genetic prion diseases related to octapeptide repeat insertions, the biomarker sensitivity correlated with the number of repeats. New genetic prion disease-specific cut-offs for 14-3-3, t-tau and α-synuclein were calculated. Disease duration in genetic Creutzfeldt-Jakob disease-E200K, Gerstmann-Sträussler-Scheinker-P102L and fatal familial insomnia was highly dependent on PRNP codon 129 MV polymorphism and was significantly associated with biomarker levels. In a large cohort of genetic prion diseases, the simultaneous analysis of CSF prion disease biomarkers allowed the determination of new mutation-specific cut-offs improving the discrimination of genetic prion disease cases and unveiled genetic prion disease-specific associations with disease duration.


Assuntos
Síndrome de Creutzfeldt-Jakob , Insônia Familiar Fatal , Doenças Priônicas , Príons , Biomarcadores/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/genética , Humanos , Insônia Familiar Fatal/genética , Doenças Priônicas/diagnóstico , Doenças Priônicas/genética , Proteínas Priônicas/genética , Príons/genética , alfa-Sinucleína
10.
BMC Public Health ; 23(1): 138, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658494

RESUMO

OBJECTIVE: Compared with other regions in the world, the transmission characteristics of the COVID-19 epidemic in Africa are more obvious, has a unique transmission mode in this region; At the same time, the data related to the COVID-19 epidemic in Africa is characterized by low data quality and incomplete data coverage, which makes the prediction method of COVID-19 epidemic suitable for other regions unable to achieve good results in Africa. In order to solve the above problems, this paper proposes a prediction method that nests the in-depth learning method in the mechanism model. From the experimental results, it can better solve the above problems and better adapt to the transmission characteristics of the COVID-19 epidemic in African countries. METHODS: Based on the SIRV model, the COVID-19 transmission rate and trend from September 2021 to January 2022 of the top 15 African countries (South Africa, Morocco, Tunisia, Libya, Egypt, Ethiopia, Kenya, Zambia, Algeria, Botswana, Nigeria, Zimbabwe, Mozambique, Uganda, and Ghana) in the accumulative number of COVID-19 confirmed cases was fitted by using the data from Worldometer. Non-autoregressive (NAR), Long-short term memory (LSTM), Autoregressive integrated moving average (ARIMA) models, Gaussian and polynomial functions were used to predict the transmission rate ß in the next 7, 14, and 21 days. Then, the predicted transmission rate ßs were substituted into the SIRV model to predict the number of the COVID-19 active cases. The error analysis was conducted using root-mean-square error (RMSE) and mean absolute percentage error (MAPE). RESULTS: The fitting curves of the 7, 14, and 21 days were consistent with and higher than the original curves of daily active cases (DAC). The MAPE between the fitted and original 7-day DAC was only 1.15% and increased with the longer of predict days. Both the predicted ß and DAC of the next 7, 14, and 21 days by NAR and LSTM nested models were closer to the real ones than other three ones. The minimum RMSEs for the predicted number of COVID-19 active cases in the next 7, 14, and 21 days were 12,974, 14,152, and 12,211 people, respectively when the order of magnitude for was 106, with the minimum MAPE being 1.79%, 1.97%, and 1.64%, respectively. CONCLUSION: Nesting the SIRV model with NAR, LSTM, ARIMA methods etc. through functionalizing ß respectively could obtain more accurate fitting and predicting results than these models/methods alone for the number of confirmed COVID-19 cases in Africa in which nesting with NAR had the highest accuracy for the 14-day and 21-day predictions. The nested model was of high significance for early understanding of the COVID-19 disease burden and preparedness for the response.


Assuntos
COVID-19 , Epidemias , Humanos , COVID-19/epidemiologia , Algoritmos , Egito , África do Sul , Previsões , Modelos Estatísticos
11.
Biochem Genet ; 61(4): 1509-1527, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36645555

RESUMO

In this study, machine learning-based multiple bioinformatics analysis was carried out for the purpose of the deep and efficient mining of high-throughput transcriptomics data from the TCGA database. Compared with normal colon tissue, 2469 genes were significantly differentially expressed in colon cancer tissue. Gene functional annotation and pathway analysis suggested that most DEGs were functionally related to the cell cycle and metabolism. Weighted gene co-expression network analysis revealed a significant module and the enriched genes that were closely related to fatty acid degradation and metabolism. Based on colon cancer progression, the trend analysis highlighted that several gene sets were significantly correlated with disease development. At the same time, the most specific genes were functionally related to cancer cell features such as the high performance of DNA replication and cell division. Moreover, survival analysis and target drug prediction were performed to prioritize reliable biomarkers and potential drugs. In consideration of a combination of different evidence, four genes (ACOX1, CPT2, CDC25C and PKMYT1) were suggested as novel biomarkers in colon cancer. The potential biomarkers and target drugs identified in our study may provide new ideas for colonic-related prevention, diagnosis, and treatment; therefore, our results have high clinical value for colon cancer.


Assuntos
Neoplasias do Colo , Transcriptoma , Humanos , Simulação de Acoplamento Molecular , Perfilação da Expressão Gênica/métodos , Biomarcadores , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Neoplasias do Colo/terapia , Biologia Computacional/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética
12.
Allergol Immunopathol (Madr) ; 51(1): 37-43, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36617820

RESUMO

OBJECTIVE: To reveal the possible effects of decursin on viability, oxidative stress, and inflammatory response in lipopolysaccharide (LPS)-treated human bronchial epithelial cells-2B (BEAS-2B) and human pulmonary artery endothelial cells (HPAEC) cells, and revealed the potential mechanisms. METHODS: LPS was used to induce acute lung injury (ALI) in normal human lung epithelial cells, including BEAS-2B and HPAEC cells. Cell viability and apoptosis in response to LPS and decursin in BEAS-2B and HPAEC cells were, respectively, evaluated by MTT colorimetric and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The oxidative stress and inflammatory response in LPS-treated BEAS-2B and HPAEC cells were detected by enzyme-linked-immunosorbent serologic assay. In addition, the role of decursin in nuclear -factor-kappa B (NF-κB) activation was analyzed by immunoblot and immunofluorescence assays. RESULTS: Our data revealed that decursin could alleviate the viability of LPS-induced BEAS-2B and HPAEC cells. Decursin could also reduce LPS-induced oxidative stress in BEAS-2B and HPAEC cells. In addition, it could reduce LPS-induced inflammation in BEAS-2B and HPAEC cells. Mechanically, decursin suppressed the activation of NF-κB pathway. CONCLUSION: Decursin suppressed NF-κB pathway, and therefore alleviated ALI.


Assuntos
Lesão Pulmonar Aguda , NF-kappa B , Humanos , NF-kappa B/metabolismo , Lipopolissacarídeos/efeitos adversos , Células Endoteliais/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Pulmão , Células Epiteliais
13.
Int J Mol Sci ; 24(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37445739

RESUMO

Small open reading frames (sORFs) are often overlooked features in genomes. In the past, they were labeled as noncoding or "transcriptional noise". However, accumulating evidence from recent years suggests that sORFs may be transcribed and translated to produce sORF-encoded polypeptides (SEPs) with less than 100 amino acids. The vigorous development of computational algorithms, ribosome profiling, and peptidome has facilitated the prediction and identification of many new SEPs. These SEPs were revealed to be involved in a wide range of basic biological processes, such as gene expression regulation, embryonic development, cellular metabolism, inflammation, and even carcinogenesis. To effectively understand the potential biological functions of SEPs, we discuss the history and development of the newly emerging research on sORFs and SEPs. In particular, we review a range of recently discovered bioinformatics tools for identifying, predicting, and validating SEPs as well as a variety of biochemical experiments for characterizing SEP functions. Lastly, this review underlines the challenges and future directions in identifying and validating sORFs and their encoded micropeptides, providing a significant reference for upcoming research on sORF-encoded peptides.


Assuntos
Genoma , Peptídeos , Fases de Leitura Aberta , Peptídeos/genética , Peptídeos/química , Biologia Computacional , Micropeptídeos
14.
Proteomics ; 22(4): e2100115, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34713569

RESUMO

Allotetraploid is a new species produced by distant hybridization between red crucian carp (Carassius auratus red var., abbreviated as RCC) and common carp (Cyprinus carpio L., abbreviated as CC). There is a significant difference in growth rate between allotetraploid and its parents. However, the underlying molecular mechanism is largely unknown. In this study, to find direct evidence associated with metabolism and growth rate in protein level, we performed quantitative proteomics analysis on liver tissues between allotetraploid and its parents. A total of 2502 unique proteins were identified and quantified by SWATH-MS in our proteomics profiling. Subsequently, comprehensive bioinformatics analyses including gene ontology enrichment analysis, pathway and network analysis, and protein-protein interaction analysis (PPI) were conducted based on differentially expressed proteins (DEPs) between allotetraploid and its parents. The results revealed several significant DEPs involved in metabolism pathways in liver. More specifically, the integrative analysis highlighted that the DEPs ACSBG1, OAT, and LDHBA play vital roles in metabolism pathways including "pentose phosphate pathway," "TCA cycle," and "glycolysis and gluconeogenesis." These could directly affect the growth rate in fresh water fishes by regulating the metabolism, utilization, and exchange of substance and energy. Since the liver is the central place for metabolism activity in animals, we firstly established the comprehensive and quantitative proteomics knowledge base for liver tissue from freshwater fishes, our study may serve as an irreplaceable reference for further studies regarding fishes' culture and growth.


Assuntos
Carpas , Animais , Carpa Dourada/genética , Fígado , Proteômica
15.
Clin Infect Dis ; 74(4): 630-638, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34043784

RESUMO

BACKGROUND: Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death. METHODS: A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses. RESULTS: Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78-23.33), presence of underlying disease (1.33; 1.19-1.49), worse case severity (severe: 3.86; 3.15-4.73; critical: 11.34; 9.22-13.95), and near-epicenter region (Hubei: 2.64; 2.11-3.30; Wuhan: 6.35; 5.04-8.00). CFR increased from 0.35% (30-39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%). CONCLUSIONS: Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.


Assuntos
COVID-19 , China/epidemiologia , Surtos de Doenças , Humanos , Modelos de Riscos Proporcionais , Fatores de Risco , SARS-CoV-2
16.
J Med Virol ; 94(9): 4548-4553, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35595682

RESUMO

Data on sofosbuvir-based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti-HCV antibody during the 1-year follow-up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow-up year one. In conclusion, this case series study found that sofosbuvir-based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir-based therapy as a reference when similar severe CHC situations are encountered during clinical practice.


Assuntos
Hepatite C Crônica , Sofosbuvir , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Fluorenos/uso terapêutico , Genótipo , Hepacivirus/genética , Humanos , Recém-Nascido , Gravidez , Gestantes , Sofosbuvir/uso terapêutico , Resultado do Tratamento
17.
Langmuir ; 38(46): 14153-14161, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36342371

RESUMO

Tribocatalysis, as a new approach in environmental purification, has drawn increasing attention in the past few years. In this work, we successfully convert mechanical energy to chemical energy by Bi12TiO20, which was synthesized by a hydrothermal method. Under magnetic stirring, electrons transfer from the surface of Bi12TiO20 to the polytetrafluoroethylene-sealed magnetic bar due to their friction. Moreover, the holes that remain on Bi12TiO20 provide oxidation properties in the process for organic matter degradation. According to a series of tests, it is noticed that the shape of the stirring bar and the material of the reaction vessel have a remarkable influence on the removal efficiency of contaminants. Simultaneously, multiple tests reveal the high stability of Bi12TiO20. A great potential for Bi12TiO20 to control water pollutants under dark conditions during collection of ambient mechanical energy was clearly demonstrated in this study.

18.
BMC Public Health ; 22(1): 1922, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36243709

RESUMO

OBJECTIVE: To evaluate the feasibility and performance of self-collected vaginal swab samples for HPV screening among women in Lagos, Nigeria. METHODS: A cross-sectional study was implemented from March to August 2020 among sexually active women. Study participants provided same-day paired vaginal swab samples. Medic-sampling and poster-directed self-sampling methods were used to collect the two samples per participant. A real-time PCR assay detected HPV 16, HPV 18, other-high-risk (OHR) HPV, and the human ß-globin gene. The self-collected samples' sensitivity, specificity, and accuracy were determined against the medic-collected samples using the MedCalc Online Diagnostic Calculator. RESULTS: Of the 213 women aged 16 ~ 63-year-old recruited, 187 (88%) participants had concordant results, while 26 (12%) participants had discordant results. Among the 187 concordant results, 35 (19%) were HPV positive, 150 (80%) participants were HPV negative, and two (1%) were invalid. 18 (69%) out of the 26 discordant samples were invalid. The self-collected sample was invalid for 14 (54%) participants. Two (8%) medic-collected samples were invalid. Compared to the medic-collected sample, the self-collected sample was 89.80% (95% CI: 77.77 ~ 96.60%) sensitive and 98.21% (95% CI: 94.87 ~ 99.63%) specific, with an accuracy of 96.31% (95% CI: 92.87 ~ 98.40%). The mean age for HPV positive and negative participants were 39 and 40, respectively, with an ANOVA p-value of 0.3932. The stratification of HPV infection by the age group was not statistically significant (P > 0.05). CONCLUSIONS: With high accuracy of 96%, self-collected sampling is adequate when tested with real-time PCR and may increase the uptake of HPV testing. Though more self-collected samples were invalid than medic-collected samples, most likely due to poor collection, they could be identified for repeat testing. Future implementation can avoid this error with improved guidance and awareness.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Estudos Transversais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Nigéria , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/métodos , Globinas beta
19.
Molecules ; 27(16)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36014456

RESUMO

Much attention has been paid to developing effective visible light catalytic technologies for VOC oxidation without requiring extra energy. In this paper, a series of sponge-based catalysts with rich three-dimensional porosity are synthesized by combining MnOx and graphitic carbon nitride (GCN) with commercial melamine sponges (MS) coated with polydopamine (PDA), demonstrating excellent photothermal catalytic performance for formaldehyde (HCHO). The three-dimensional porous framework of MS can provide a good surface for material modification and a reliable interface for gas-solid interaction. The grown layer of PDA framework not only increases the near-infrared wavelength absorption for improving the light-to-heat conversion of catalysts, but also brings excellent adhesion for the subsequent addition of MnOX and GCN. The efficient formaldehyde oxidation is attributed to the sufficient oxygen vacancies generated by co-loaded MnOX and GCN, which is conducive to the activation of more O2- in the oxidation process. As the surface temperature of catalyst rapidly increases to its maximum value at ca. 115 °C under visible light irradiation, the HCHO concentration drops from 160 ppm to 46 ppm within 20 min. The reaction mechanism is certified as a classical Mars-van Krevelen mechanism based on the photo-induced thermal catalysis process.

20.
Clin Infect Dis ; 72(2): 332-339, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33501949

RESUMO

The epidemic of novel coronavirus disease was first reported in China in late December 2019 and was brought under control after some 2 months in China. However, it has become a global pandemic, and the number of cases and deaths continues to increase outside of China. We describe the emergence of the pandemic, detail the first 100 days of China's response as a phase 1 containment strategy followed by phase 2 containment, and briefly highlight areas of focus for the future. Specific, simple, and pragmatic strategies used in China for risk assessment, prioritization, and deployment of resources are described. Details of implementation, at different risk levels, of the traditional public health interventions are shared. Involvement of society in mounting a whole country response and challenges experienced with logistics and supply chains are described. Finally, the methods China is employing to cautiously restart social life and economic activity are outlined.


Assuntos
COVID-19 , China/epidemiologia , Humanos , Pandemias , Saúde Pública , SARS-CoV-2
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