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1.
Artigo em Inglês | MEDLINE | ID: mdl-34221254

RESUMO

Background: COVID-19 has infected over 35 million people worldwide and led to over 1 million deaths. Several risk factors that increase COVID-19 severity have emerged, including age and a history of cardiovascular disease, hypertension, or kidney disease. However, a number of outstanding questions persist, including whether the above comorbidities correlate with increased mortality from COVID-19 or whether age is a significant confounding variable that accounts for the observed relationship between COVID-19 severity and other comorbidities. Methods and Findings: We conducted a systematic review and meta-analysis of studies documenting COVID-19 patients with hypertension, cardiovascular disease, cerebrovascular disease, or chronic kidney disease. We classified COVID-19 cases into severe/non-severe or deceased/surviving and calculated the odds ratio (OR) for each of the four comorbidities in these cohorts. 36 studies, comprising 22,573 patients, are included in our meta-analysis. We found that hypertension is the most prevalent comorbidity in deceased COVID-19 patients (55.4%; CI: 49.4 - 61.3%), followed by cardiovascular disease (30.7%; CI: 22.6 - 38.8%), cerebrovascular disease (13.4%; CI: 9.12- 19.2%), then chronic kidney disease (9.05%; CI: 5.57-15.0%). The risk of death is also significantly higher for patients with these comorbidities, with the greatest risk factor being chronic kidney disease (OR: 8.86; CI: 5.27-14.89), followed by cardiovascular disease (OR: 6.87; CI: 5.56-8.50), hypertension (OR: 4.87; CI: 4.19-5.66), and cerebrovascular disease (OR: 4.28; CI: 2.86-6.41). These risks are significantly higher than previously reported, while correlations between comorbidities and COVID-19 severity are similar to previously reported figures. Using meta-regression analysis with age as a moderating variable, we observed that age contributes to the observed risks but does not explain them fully. Conclusions: In this meta-analysis, we observed that cardiovascular, cerebrovascular, and kidney-related comorbidities in COVID-19 significantly contributes to greater risk of mortality and increased disease severity. We also demonstrated that age may not be a confounder to these associations.

2.
Nucleic Acids Res ; 49(13): 7361-7374, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34181729

RESUMO

N6-methyladenosine (m6A) is a common modification on endogenous RNA transcripts in mammalian cells. Technologies to precisely modify the RNA m6A levels at specific transcriptomic loci empower interrogation of biological functions of epitranscriptomic modifications. Here, we developed a bidirectional dCasRx epitranscriptome editing platform composed of a nuclear-localized dCasRx conjugated with either a methyltransferase, METTL3, or a demethylase, ALKBH5, to manipulate methylation events at targeted m6A sites. Leveraging this platform, we specifically and efficiently edited m6A modifications at targeted sites, reflected in gene expression and cell proliferation. We employed the dCasRx epitranscriptomic editor system to elucidate the molecular function of m6A-binding proteins YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3), revealing that YTHDFs promote m6A-mediated mRNA degradation. Collectively, our dCasRx epitranscriptome perturbation platform permits site-specific m6A editing for delineating of functional roles of individual m6A modifications in the mammalian epitranscriptome.


Assuntos
Adenosina/análogos & derivados , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Metiltransferases/metabolismo , RNA Mensageiro/metabolismo , Adenosina/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Proteínas Associadas a CRISPR/genética , Proliferação de Células , Células Cultivadas , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Metiltransferases/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Processamento Pós-Transcricional do RNA , RNA Mensageiro/química , Proteínas de Ligação a RNA/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Transcriptoma
3.
Environ Sci Pollut Res Int ; 28(14): 17405-17416, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33394394

RESUMO

Wheat is the second most important food crop worldwide, which is prone to accumulate cadmium (Cd). Accumulation of Cd in wheat grains depends not only on wheat genotype, but also largely on the availability of soil Cd and its internal distribution. In this study, several experiments were used to achieve low-grain Cd content: a field trial for wheat genotype screening, a soil incubation experiment to test passivation effect of bamboo biochar on soil Cd, and a soil pot experiment to examine bamboo biochar effect on wheat grain accumulation. The results showed that of the 243 wheat cultivars tested, the variation range of grain Cd content was 0.365-1.243 mg/kg, in a field with soil Cd of 3 mg/kg. The application of bamboo biochar reduced soil Cd availability, among which 5.0% bamboo biochar treatment had the greatest effect. The content of available Cd in soil treated with 5.0% bamboo biochar decreased by 0.32 mg/kg compared with the control in a 120-day incubation experiment. Effect of bamboo biochar (0, 0.1%, 1.0%, and 5.0%) on reducing grain Cd content in two wheat genotypes (Mianyou-1 and 1279-9) was investigated. The application of bamboo biochar decreased Cd uptake by plants, while distribution of Cd in different wheat plant parts was more controlled by the plant genetic characteristics. Compared with the control, Cd content in roots, straw, and grains was decreased by 34.06% (P < 0.05), 21.57%, and 23.33%, respectively, in low-grain Cd wheat cultivar 1279-9 by 5% bamboo biochar application. Overall, the combination of low-grain Cd accumulation wheat and bamboo biochar may be a feasible strategy to lessen grain Cd accumulation in Cd-contaminated soils.


Assuntos
Sasa , Poluentes do Solo , Cádmio/análise , Carvão Vegetal , Grão Comestível/química , Genótipo , Solo , Poluentes do Solo/análise , Triticum/genética
4.
BMC Med Inform Decis Mak ; 20(1): 247, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993652

RESUMO

BACKGROUND: The recent Coronavirus Disease 2019 (COVID-19) pandemic has placed severe stress on healthcare systems worldwide, which is amplified by the critical shortage of COVID-19 tests. METHODS: In this study, we propose to generate a more accurate diagnosis model of COVID-19 based on patient symptoms and routine test results by applying machine learning to reanalyzing COVID-19 data from 151 published studies. We aim to investigate correlations between clinical variables, cluster COVID-19 patients into subtypes, and generate a computational classification model for discriminating between COVID-19 patients and influenza patients based on clinical variables alone. RESULTS: We discovered several novel associations between clinical variables, including correlations between being male and having higher levels of serum lymphocytes and neutrophils. We found that COVID-19 patients could be clustered into subtypes based on serum levels of immune cells, gender, and reported symptoms. Finally, we trained an XGBoost model to achieve a sensitivity of 92.5% and a specificity of 97.9% in discriminating COVID-19 patients from influenza patients. CONCLUSIONS: We demonstrated that computational methods trained on large clinical datasets could yield ever more accurate COVID-19 diagnostic models to mitigate the impact of lack of testing. We also presented previously unknown COVID-19 clinical variable correlations and clinical subgroups.


Assuntos
Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Influenza Humana/diagnóstico , Aprendizado de Máquina , Pneumonia Viral/diagnóstico , Betacoronavirus , COVID-19 , Teste para COVID-19 , Simulação por Computador , Infecções por Coronavirus/classificação , Conjuntos de Dados como Assunto , Diagnóstico Diferencial , Feminino , Humanos , Vírus da Influenza A , Masculino , Pandemias/classificação , Pneumonia Viral/classificação , SARS-CoV-2 , Sensibilidade e Especificidade
5.
Cancers (Basel) ; 12(9)2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32899474

RESUMO

Although 1 in 9 American men will receive a diagnosis of prostate cancer (PC), most men with this diagnosis will not die from it, as most PCs are indolent. However, there is a subset of patients in which the once-indolent PC becomes metastatic and eventually, fatal. In this study, we analyzed microbial compositions of intratumor bacteria in PC to determine the influence of the microbiome on metastatic growth. Using large-scale RNA-sequencing data and corresponding clinical data, we correlated the abundance of microbes to immune pathways and PC risk factors, identifying specific microbes that either significantly deter or contribute to cancer aggressiveness. Interestingly, most of the microbes we found appeared to play anti-tumor roles in PC. Since these anti-tumor microbes were overrepresented in tumor samples, we believe that microbes thrive in the tumor microenvironment, outcompete cancer cells, and directly mitigate tumor growth by recruiting immune cells. These include Listeria monocytogenes, Methylobacterium radiotolerans JCM 2831, Xanthomonas albilineans GPE PC73, and Bradyrhizobium japonicum, which are negatively correlated with Gleason score, Tumor-Node-Metastasis (TNM) stage, prostate-specific antigen (PSA) level, and Androgen Receptor (AR) expression, respectively. We also identified microbes that contribute to tumor growth and are positively correlated with genomic alterations, dysregulated immune-associated (IA) genes, and prostate cancer stem cells (PCSC) genes.

6.
Gene ; 738: 144485, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32087272

RESUMO

Impairment of neurogenesis is thought to be one of the important mechanisms underlying radiation-induced cognitive decline. Self-renewal and differentiation of neural stem cells (NSCs) are important components of neurogenesis. It has been well established that autophagy plays an important role in neurodegenerative conditions, however, its role in radiation-induced cognitive decline remains unclear. Our previous studies have found that ionizing radiation (IR) induces autophagy in mouse neurons, and minocycline, an antibiotic that can cross the blood-brain barrier, protects neurons from radiation-induced apoptosis through promoting autophagy, thus may contribute to the improvement of mouse cognitive performance after whole-brain irradiation. In the present study, we investigated whether autophagy is involved in radiation-induced damage in self-renewal and differentiation of NSCs. We found that NSCs were extremely sensitive to IR. Irradiation induced autophagy in NSCs in a dose-dependent manner. Atg7 knockdown significantly decreased autophagy, thus increased the apoptosis levels in irradiated NSCs, suggesting that autophagy protected NSCs from radiation-induced apoptosis. Moreover, compared with the negative control NSCs, the neurosphere size was significantly reduced and the neuronal differentiation was notably inhibited in Atg7-deficient NSCs after irradiation, indicating that autophagy defect could exacerbate radiation-induced reduction in NSC self-renewal and differentiation potential. In conclusion, down-regulating autophagy by selective Atg7 knockdown in NSCs enhanced radiation-induced NSC damage, suggesting an important protective role of autophagy in maintaining neurogenesis. Along with the protective effect of autophagy on irradiated neurons, our results on NSCs not only shed the light on the involvement of autophagy in the development of radiation-induced cognitive decline, but also provided a potential target for preventing cognitive impairment after cranial radiation exposure.


Assuntos
Proteína 7 Relacionada à Autofagia/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/efeitos da radiação , Animais , Apoptose/efeitos da radiação , Autofagia/efeitos da radiação , Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Células Cultivadas , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/citologia , Neurogênese/efeitos da radiação , Neurônios/efeitos da radiação , Gravidez , Radiação Ionizante
7.
Oxid Med Cell Longev ; 2019: 8636835, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911351

RESUMO

Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer's disease (AD). The aim of the study was undertaken to investigate the antiamnesic effects of the two drugs alone and in combination through in vivo models of the Morris water maze along with in vitro antioxidants, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The potential mechanisms were speculated by the activities of acetylcholine (ACh), AChE, superoxide dismutase (SOD), and malondialdehyde (MDA) and the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB). The combination group showed a concentration-dependent inhibition of cholinesterase and antioxidation. As far as its mechanism was concerned, the combination of two drugs exerted excellent effects on oxidative stress, cholinergic pathway damage, and inactivation of the BDNF-TrkB signaling pathway. Additionally, to elucidate the binding mechanism of GT active ingredients into the structure of AChE, the results of molecular docking studies indicated that hydrogen and/or hydrophobic bonds might play an important role in their binding process. Thus, the combination of drugs could treat AD perfectly and further verify the scientific rationality of clinical medication.


Assuntos
Amnésia/tratamento farmacológico , Donepezila/uso terapêutico , Ginkgo biloba/química , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Acetilcolina/metabolismo , Acetilcolinesterase , Amnésia/patologia , Animais , Benzotiazóis/química , Compostos de Bifenilo/química , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Inibidores da Colinesterase/farmacologia , Transtornos Cognitivos/tratamento farmacológico , Donepezila/farmacologia , Quimioterapia Combinada , Ginkgolídeos/química , Ligantes , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Picratos/química , Extratos Vegetais/farmacologia , Receptor trkB/metabolismo , Escopolamina , Ácidos Sulfônicos/química , Superóxido Dismutase/metabolismo , Comprimidos
8.
J Clin Lab Anal ; 33(2): e22694, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30338547

RESUMO

BACKGROUND: Serological tests are indispensable in the diagnosis of early infection. At present, only procalcitonin (PCT) and C-reactive protein (CRP) are commonly used in clinical practice. Recently, serum amyloid A1 (SAA1) and heparin binding protein (HBP) have been shown to be new biomarkers, because SAA1 is highly sensitive and specific for viral infections, and HBP is predictive for septic shock. In this study, PCT, CRP, HBP, and SAA1 were detected in different combinations to improve the diagnostic accuracy of early infection using the biotin-avidin amplifying system-based time-resolved fluorescent immunoassay (BA-TRFIA). METHODS: A time-resolved fluorescent immunoassay for PCT, CRP, HBP, and SAA1 was developed and then tested in a clinical setting. All experiments were carried out using the DR6608 time-resolved fluorescent immunoassay analyzer. RESULTS: The cutoff values of PCT, CRP, HBP, and SAA1 were 0.05 µg/L, 5.59 mg/L, 3.83 µg/L, and 1.56 mg/L, respectively. The area under the ROC curve (AUC) showed that PCT Ëƒ SAA1 Ëƒ CRP Ëƒ HBP > 0.8. A methodological comparison of the results showed that a combination of the four biomarkers had the highest accuracy for the diagnosis of infectious diseases. CONCLUSION: The time-resolved fluorescent immunoassay-based combined detection of PCT, CRP, HBP, and SAA1 was shown to significantly improve the diagnostic accuracy of early infection. Thus, our results indicate that combined detection based on BA-TRFIA may represent a promising strategy in the clinical diagnosis of infection.


Assuntos
Peptídeos Catiônicos Antimicrobianos/sangue , Infecções Bacterianas/diagnóstico , Proteína C-Reativa/análise , Proteínas de Transporte/sangue , Imunofluorescência/métodos , Pró-Calcitonina/sangue , Proteína Amiloide A Sérica/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/sangue , Biomarcadores/sangue , Proteínas Sanguíneas , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Viroses/sangue , Viroses/diagnóstico , Adulto Jovem
9.
Biomed Res Int ; 2018: 4598067, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30276207

RESUMO

In the present study, the process of ultrasound-assisted extraction (UAE) followed by macroporous resin purification was successfully developed to achieve maximal recovery of functional components (flavonoids and ginkgolides) with minimal contents of toxic components (alkylphenols) from Ginkgo biloba leaves. Three effective extracted factors including HAc%, EtOH%, and UAE power were screened by Plackett-Burman design (PBD). The important variables were further optimized by rotatable central composite design (RCCD). By combination of PBD and RCCD, the resulting optimal UAE conditions were as follows: HAc% of 1.8%, EtOH% of 63%, ultrasound power of 303 W, G. biloba leaves powder amount of 1.0 g (solvent-to-solid ratio 40 mL/g), particle size of 60 mesh, extraction time of 40 min, and extraction temperature of 45°C. Under the optimum conditions, the yield of flavonoids was 25.1 ± 0.81 mg/g, ginkgolides was 10.6 ± 0.57 mg/g, and alkylphenols was 3.96 ± 0.31 mg/g. Moreover, the further enriching the functional components and removing toxic components from the obtained extracts of G. biloba leaves using the above optimum UAE condition was successfully achieved by macroporous resin DA-201. After column adsorption and desorption on DA-201, the content of total flavonoids was 36.51 ± 1.53%, ginkgolides was 13.24 ± 0.85%, and alkylphenols was 7.0 ± 1.0 µg/g from the obtained dry extracts (drug to extract ratio of 45-50:1) of G. biloba leaves which were complied with Chinese pharmacopoeias.


Assuntos
Flavonoides/isolamento & purificação , Ginkgo biloba/química , Folhas de Planta/química , Ginkgolídeos , Extratos Vegetais , Resinas Vegetais , Ondas Ultrassônicas
10.
Molecules ; 23(5)2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29702576

RESUMO

In the present study, the process of ultrasonic assisted enzymatic extraction (UAEE), followed by macroporous resin purification, was successfully developed to achieve maximal recovery of flavonoids and ginkgolides from Ginkgo biloba fallen leaves (GBFL). Three effective extracted factors, including UAE power, EtOH%, and the amount of cellulase were screened by Plackett⁻Burman design (PBD). The important variables were further optimized by rotatable central composite design (RCCD). After the combination of PBD and RCCD, the resulting optimal UAEE conditions were as follows: UAE power of 218 W; EtOH% of 68%; the amount of cellulase of 8.4 mg; UAE temperature of 40 °C; UAE time of 20 min; pH of 5.0; and, sample particle size of 40 mesh. Under the optimum conditions; the yields of flavonoids were 0.74 ± 0.05% (n = 3) and ginkgolides was 0.42 ± 0.06% (n = 3), which were close to the predicted values. Moreover, the further enriching flavonoids and ginkgolides from the obtained GBFL extracts using the above optimum UAEE condition was successfully achieved by macroporous resin DA-201. After column adsorption and desorption on DA-201; the percentage of total flavonoids was (25.36 ± 1.03)%; ginkgolides was (12.43 ± 0.85)% and alkylphenols was (0.003 ± 0.0005)% from the obtained dry extracts of GBFL which were complied with Chinese pharmacopoeias. Therefore, the present study provided a convenient and efficient method for extraction and purification of flavonoids and ginkgolides from waste GBFL.


Assuntos
Celulase/metabolismo , Fracionamento Químico/métodos , Flavonoides/isolamento & purificação , Ginkgo biloba/química , Ginkgolídeos/isolamento & purificação , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Folhas de Planta/química , Porosidade , Resinas Vegetais/isolamento & purificação , Sonicação , Temperatura
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