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1.
Eur J Clin Invest ; 53(11): e14079, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37589179

RESUMO

BACKGROUND: Evidence supports the observational associations of human blood metabolites with the risk of severe COVID-19. However, little is known about the potential pathological mechanisms and the analysis of blood metabolites may offer a better understanding of the underlying biological processes. METHODS: We applied a two-sample Mendelian randomization (MR) analysis to evaluate relationships between 486 blood metabolites and the risk of severe COVID-19. The inverse-variance weighted (IVW) model was used as the primary two-sample MR analysis method to estimate the causal relationship of the exposure on the outcome. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. RESULTS: Four hunderd and eighty six metabolites were included for MR analysis following rigorous genetic variants selection. After MR analyses and sensitivity analysis filtration, we found weak evidence of an association between 3-hydroxybutyrate (odds ratio [OR] = 1.21, 95% CI, 1.07-1.38, p = .0036) and the risk of severe COVID-19. A series of sensitivity analyses have been carried out to confirm the rigidity of the above results. CONCLUSION: This study suggested a causal relationship between 3-hydroxybutyrate and the severity of COVID-19, thus providing novel insights into biomarkers and pathways for COVID-19 prevention and clinical interventions.

2.
Crit Care ; 27(1): 476, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053214

RESUMO

BACKGROUND: Observational studies have indicated a potential association between autoimmune diseases and the occurrence of sepsis, with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown. METHODS: In the Mendelian randomization (MR) study, we accessed exposure Genome-wide association study (GWAS) data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium. GWAS data for sepsis and its 28-day mortality were obtained from MRC-IEU. We employed univariable, multivariable, and reverse MR analyses to explore potential associations between autoimmune disorders and sepsis and its 28-day mortality. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between autoimmune disorders and sepsis. Afterward, we conducted an observational analysis to further explore the relationship between autoimmune disease and occurrence as well as 28-day mortality of sepsis using a real-world database (the MIMIC-IV database). A cohort of 2537 patients diagnosed with autoimmune disease were extracted from the database for analysis. Multivariable logistic regression models were used to confirm the association between autoimmune diseases and the occurrence of sepsis, as well as the 28-day mortality associated with sepsis. RESULTS: In univariable MR analysis, there appeared to be causal relationships between genetically predicted type 1 diabetes (OR = 1.036, 95% CI = 1.023-1.048, p = 9.130E-09), rheumatoid arthritis (OR = 1.077, 95% CI = 1.058-1.097, p = 1.00E-15) and sepsis, while a potential causal link was observed between celiac disease and sepsis (OR = 1.013, 95% CI = 1.002-1.024, p = 0.026). In a subsequent multivariable MR analysis, only rheumatoid arthritis was found to be independently associated with the risk of sepsis (OR = 1.138, 95% CI = 1.044-1.240, p = 3.36E-03). Furthermore, there was no causal link between autoimmune disorders and 28-day mortality from sepsis. In reverse MR analysis, sepsis was suggested to potentially trigger the onset of psoriasis (OR = 1.084, 95% CI = 1.040-1.131, p = 1.488E-04). In the real-world observational study, adjusting for multiple confounders, rheumatoid arthritis (OR = 1.34, 95% CI = 1.11-1.64, p = 0.003) and multiple sclerosis (OR = 1.31, 95% CI = 1.03-1.68, p = 0.02) were associated with a higher risk of sepsis. In addition, we did not find that autoimmune diseases were associated with 28-day mortality from sepsis. CONCLUSION: Both in observational and MR analysis, only rheumatoid arthritis is highly correlated with occurrence of sepsis. However, autoimmune disease was not associated with an increased 28-day mortality in patient with sepsis. Sepsis may increase the risk of developing psoriasis.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Psoríase , Sepse , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Artrite Reumatoide/complicações , Artrite Reumatoide/genética , Sepse/complicações , Sepse/genética
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(11): 1187-1191, 2022 Nov 10.
Artigo em Zh | MEDLINE | ID: mdl-36317201

RESUMO

OBJECTIVE: To analyze the Z values of true and false positive cases by non-invasive prenatal testing (NIPT) in order to improve its accuracy in clinical practice. METHODS: Results of 24 384 NIPT tests were reviewed. For cases with high risks for trisomies 21, 18 and 13, the range of Z values in true and false positive cases was analyzed and discussed. RESULTS: A total of 335 high-risk cases were identified by NIPT, among which 256 had elected prenatal diagnosis, 153 (59.77%) were verified as true positives, and 103 (40.23%) were false positives, and the area under the curve (AUC) was 0.9994. For NIPT screening, the positive predictive value (PPV) for trisomy 21 was 100% when Z>13, regardless if the pregnant woman was over 35. When 335 and about 41.6% (5/12) for those<35. For trisomy 18, the PPV was 100% when Z>13, and only 14.3% (1/7) when 3

Assuntos
Transtornos Cromossômicos , Síndrome de Down , Feminino , Gravidez , Humanos , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/genética , Trissomia/diagnóstico , Trissomia/genética , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Transtornos Cromossômicos/genética , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Diagnóstico Pré-Natal/métodos
4.
J Org Chem ; 86(15): 10397-10406, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34283586

RESUMO

The tandem decarboxylative condensation-dimerization reaction of l-proline with 2,5-cyclohexadienones including p-quinone monoacetals, p-quinol ethers, and p-quinols is reported to provide a concise and rapid synthesis of octahydro-dipyrroloquinoline compounds. The reaction features the use of cost-effective and readily available starting materials, high efficiency, metal-free and green reaction conditions. The reaction is applied to the synthesis of incargranine B aglycone. The discovery of this reaction may suggest a biosynthetic pathway from 2,5-cyclohexadienones and proline for natural ingredients containing pyrroloquinoline moieties.


Assuntos
Cicloexenos , Prolina , Dimerização , Éteres
5.
Biochem Biophys Res Commun ; 526(2): 368-374, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32222279

RESUMO

Breast cancer (BC), the most frequent cancer in women worldwide, is extremely heterogeneous. For effective and precise treatment and to cope with drug resistance in BC, we need to find more therapeutic molecular targets. In this study, we found that the Proteasome 26S Subunit, Non-ATPase 12 (PSMD12) was upregulated in BC samples, its expression was heterogeneous among different cell lines, and high levels of PSMD12 were related to poor prognosis of BC patients. Notably, the expression of PSMD12 increased in the nucleus. Cytological experiments revealed that PSMD12 knockdown inhibited cell growth and migration, and a genome-wide CRISPR-Cas9 knockout (GeCKO) screen also confirmed that PSMD12 is a crucial gene for the growth of BC cells. Flow cytometry showed that cell apoptosis increased in the PSMD12 knockdown, and RNA-seq indicated that the apoptosis pathway was activated, and the TXNIP, GADD45A, GADD45B, RHOB, and CDKN1A pro-apoptotic genes were highly expressed, a result that was validated by RT-qPCR and Western blot. Furthermore, restoration of PSMD12 expression decreased the expression of pro-apoptotic genes. A tumor-bearing mice assay demonstrated that BC growth was arrested by reduced PSMD12 levels in vivo. Taken together, PSMD12, a subunit of 19S regulator of 26S proteasome, was identified as a potential prognostic and therapeutic molecular target for BC, which provides a new insight for developing anticancer drugs that promote apoptosis based on the targeting of the 26S proteasome complex.


Assuntos
Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Animais , Apoptose , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus
6.
Sensors (Basel) ; 20(19)2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32992678

RESUMO

Scattering hyperspectral technology is a nondestructive testing method with many advantages. Here, we propose a method to improve the accuracy of egg freshness, research the influence of incident angles of light source on the accuracy, and explain its mechanism. A variety of weak classifiers classify eggs based on the spectra after preprocessing and feature wavelength extraction to obtain three classifiers with the highest accuracy. The three classifiers are used as metamodels of stacking ensemble learning to improve the highest accuracy from 96.25% to 100%. Moreover, the highest accuracy of scattering, reflection, transmission, and mixed hyperspectral of eggs are 100.00%, 88.75%, 95.00%, and 96.25%, respectively, indicating that the scattering hyperspectral for egg freshness detection is better than that of the others. In addition, the accuracy is inversely proportional to the angle of incidence, i.e., the smaller the incident angle, the camera collects a larger proportion of scattering light, which contains more biochemical parameters of an egg than that of reflection and transmission. These results are very important for improving the accuracy of non-destructive testing and for selecting the incident angle of a light source, and they have potential applications for online non-destructive testing.


Assuntos
Ovos , Análise de Alimentos/métodos , Imageamento Hiperespectral , Aprendizado de Máquina , Luz
7.
Biochem Biophys Res Commun ; 516(1): 215-221, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31208716

RESUMO

Dysregulation of gluconeogenesis contributes to the pathogenesis of metabolic disease, such as type-2 diabetes. The role of long non-coding RNAs (lncRNAs) in the pathogenesis of diabetes has recently received increased attention. In the present study, we identified a novel lncRNA, betaine-homocysteine methyltransferase-antisense (Bhmt-AS), and examined its expression patterns under pathophysiological conditions. Our results revealed that the expression of Bhmt-AS was significantly increased in the livers of fasted and db/db mice and was induced by gluconeogenic hormonal stimuli. The Bhmt-AS was also shown to be a concordant regulator of Bhmt expression. Functionally, depletion of Bhmt-AS suppressed hepatic glucose production both in vivo and in vitro. Adenovirus-mediated hepatic knockdown of Bhmt-AS improved pyruvate tolerance, glucose tolerance, and insulin sensitivity. Furthermore, overexpression of Bhmt restored the decreased glucose production caused by knockdown of Bhmt-AS in primary hepatocytes. Taken together, we uncovered a novel antisense lncRNA (Bhmt-AS) that is co-expressed with Bhmt and concordantly and specifically regulates Bhmt expression both in vitro and in vivo to regulate hepatic gluconeogenesis.


Assuntos
Betaína-Homocisteína S-Metiltransferase/genética , Gluconeogênese , Fígado/metabolismo , RNA Longo não Codificante/genética , Animais , Células Cultivadas , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regulação para Cima
8.
Angew Chem Int Ed Engl ; 55(31): 9030-5, 2016 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-27253520

RESUMO

The development of superior non-platinum electrocatalysts for enhancing the electrocatalytic activity and stability for the oxygen-reduction reaction (ORR) and liquid fuel oxidation reaction is very important for the commercialization of fuel cells, but still a great challenge. Herein, we demonstrate a new colloidal chemistry technique for making structurally ordered PdCu-based nanoparticles (NPs) with composition control from PdCu to PdCuNi and PtCuCo. Under the dual tuning on the composition and intermetallic phase, the ordered PdCuCo NPs exhibit better activity and much enhanced stability for ORR and ethanol-oxidation reaction (EOR) than those of disordered PdCuM NPs, the commercial Pt/C and Pd/C catalysts. The density functional theory (DFT) calculations reveal that the improved ORR activity on the PdCuM NPs stems from the catalytically active hollow sites arising from the ligand effect and the compressive strain on the Pd surface owing to the smaller atomic size of Cu, Co, and Ni.

9.
Biosens Bioelectron ; 261: 116458, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38852321

RESUMO

Herein, a colorimetric-fluorescent hybrid bifunctional nanobead with Janus structure (J-cf-HBN) was synthesized via one-pot microemulsification. Oleylamine-coated AuNPs and aggregation-induced emission luminogens (AIEgens) were suggested as building blocks to obtain high-performance colorimetric-fluorescent signals. The as-prepared J-cf-HBNs were used as a signal amplification probe to construct an immunochromatographic assay (J-cf-HBNs-ICA) platform for the ultrasensitive detection of staphylococcal enterotoxin B (SEB) in milk samples. Owing to the rational spatial distribution of AuNPs and AIEgens, the J-cf-HBNs present a highly retained photoluminescence and enhanced colorimetric signals. Combined with a pair of highly affinitive anti-SEB antibodies, the J-cf-HBN-ICA platform enabled the fast naked-eye visualization and fluorescent quantitative detection of SEB in various milk matrices. Given the advantages of the dual-mode high-performance J-cf-HBNs, the proposed strip achieved a high sensitivity for SEB qualitative determination with a visual limit of detection (LOD) of 1.56 ng mL-1 and exhibited ultrasensitivity for SEB quantitative detection with a LOD of 0.09 ng mL-1, which is 139-fold lower than that of ELISA using same antibodies. In conclusion, this work provides new insights into the construction of multimode immunochromatographic methods for food safety detection in the field.


Assuntos
Técnicas Biossensoriais , Colorimetria , Enterotoxinas , Ouro , Limite de Detecção , Nanopartículas Metálicas , Leite , Leite/química , Enterotoxinas/análise , Enterotoxinas/imunologia , Enterotoxinas/isolamento & purificação , Animais , Técnicas Biossensoriais/métodos , Colorimetria/métodos , Ouro/química , Nanopartículas Metálicas/química , Corantes Fluorescentes/química , Contaminação de Alimentos/análise , Cromatografia de Afinidade/métodos , Imunoensaio/métodos
10.
Medicine (Baltimore) ; 103(10): e37315, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457585

RESUMO

Previous research has indicated that higher red blood cell distribution width (RDW) increases the risk of coronary heart disease. However, no studies have established a link between RDW and coronary heart disease in the rheumatoid arthritis population. This research aims to explore the association between RDW and coronary heart disease among individuals with rheumatoid arthritis. We selected demographic data, laboratory data, lifestyle, and medical history from the National Health and Nutrition Examination Survey (NHANES), specifically including age, gender, poverty, RDW, race, BMI, diabetes, education, coronary heart disease, hypertension, cholesterol, smoking, and drinking. RDW and coronary heart disease were found to have a positive association in the rheumatoid arthritis population (OR = 1.145, 95%CI: 1.036-1.266, P = .0098), even after adjusting for factors such as age, gender, race, education level, smoking, and drinking. Subgroup analysis showed a stronger positive association, particularly in individuals aged 55-66 years, males, and the Hispanic White population with diabetes or hypercholesterolemia. There is a significant correlation between RDW and coronary heart disease among individuals with rheumatoid arthritis.


Assuntos
Artrite Reumatoide , Doença das Coronárias , Diabetes Mellitus , Masculino , Humanos , Inquéritos Nutricionais , Estudos Transversais , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Doença das Coronárias/epidemiologia , Índices de Eritrócitos
11.
Food Chem ; 447: 138997, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38513493

RESUMO

Herein we developed a multicolor lateral flow immunoassay (LFIA) test strip for rapid and simultaneous quantitative detection of aflatoxin B1 (AFB1) and zearalenone (ZEN). Three differently colored aggregation-induced emission nanoparticles (AIENPs) were designed as LFIA signal tags, with red and green AIENPs for targeting AFB1 and ZEN at the test line, and yellow AIENPs for indicating the validity of the test strip at the control (C) line. After surface functionalization with antibodies, the developed AIENP-based multicolor LFIA allows simultaneous and accurate quantification of AFB1 and ZEN using an independent C-line assisted ratiometric signal output strategy. The detection limits of AFB1 and ZEN were 6.12 and 26 pg/mL, respectively. The potential of this method for real-world applications was well demonstrated in corn and wheat. Overall, this multicolor LFIA shows great potential for field screening of multiple mycotoxins and can be extended to rapid and simultaneous monitoring of other small molecule targets.


Assuntos
Nanopartículas Metálicas , Micotoxinas , Zearalenona , Zearalenona/análise , Aflatoxina B1/análise , Anticorpos Monoclonais , Micotoxinas/análise , Imunoensaio/métodos , Limite de Detecção , Contaminação de Alimentos/análise
12.
Int Immunopharmacol ; 126: 111295, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38048668

RESUMO

Immune dysfunction is one of the leading causes of death of sepsis. How to regulate host immune functions to improve prognoses of septic patients has always been a clinical focus. Here we elaborate on the efficacy and potential mechanism of a classical drug, thymopentin (TP5). TP5 could decrease peritoneal bacterial load, and reduce inflammatory cytokine levels both in the peritoneal lavage fluid (PLF) and serum, alleviate pathological injuries in tissue and organ, coaxed by cecal ligation and perforation (CLP) in mice, ultimately improve the prognosis of septic mice. Regarding the mechanism, using RNA-seq and flow cytometry, we found that TP5 induced peptidoglycan recognition protein 1 (PGLYRP1) expression, increased phagocytosis and restored TNF-α expression of small peritoneal macrophage (SPM) in the septic mice. This may be increased SPM's ability to clear peritoneal bacteria, thereby attenuates the inflammatory response both in the peritoneal cavity and the serum. It was shown that TP5 plays a key role in restoring the function of peritoneal macrophages to alleviate the sepsis process. We reckon that this is closely relevant to SPM phagocytosis, which might involve increased PGLYRP1 expression and restored TNF-α secretion.


Assuntos
Sepse , Timopentina , Humanos , Camundongos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo
13.
J Chromatogr A ; 1714: 464544, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38142618

RESUMO

Comprehensive and rapid analysis of secondary metabolites like saponins remains challenging. This study aimed to establish a semi-automated workflow for filtration, identification, and characterization of saikosaponins in six Bupleurum species. Radix Bupleuri, a high-sales herbal medicine, is often adulterated, restricting its quality control and applications. Two authentic Radix Bupleuri species and four major adulterants were analyzed through UHPLC-LTQ-Orbitrap-MS for targeted saikosaponin analysis. To reveal trace saikosaponins and obtain quality fragment data, a MATLAB-based process automatically enumerating "sugar chain + aglycone + side chain" combinations and deduplicating generated a predicted saikosaponin database covering all possible saikosaponins as a precursor ion list for comprehensive targeted acquisition. To focus on informative ions and reduce MS analysis workload, we utilized MATLAB to automatically filtrate the false positive ions by MS1 and MS2 spectrometry. The newly established MATLAB-assisted data acquisition approach exhibited 50 % improvement in characterization of targeted saikosaponins. Furthermore, positive and negative ionization workflows were designed for accurate saikosaponins characterization based on fragmentation rules. In total, 707 saikosaponins were characterized, including over 500 potential new compounds and previously unreported C29 aglycones. We identified 25 saikosaponins present in both authentic species but absent in adulterants as potential markers. This unprecedented comprehensive multi-origin species differentiation demonstrates the promise of MATLAB-assisted acquisition and processing to advance saponin identification and standardize the Radix Bupleuri market.


Assuntos
Bupleurum , Medicamentos de Ervas Chinesas , Ácido Oleanólico , Saponinas , Medicamentos de Ervas Chinesas/química , Bupleurum/química , Extratos Vegetais , Saponinas/análise , Ácido Oleanólico/análise , Cromatografia Líquida , Espectrometria de Massas , Íons , Cromatografia Líquida de Alta Pressão/métodos
14.
J Agric Food Chem ; 72(13): 7438-7456, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38513720

RESUMO

Aristolochic acid analogues (AAAs) are well-known toxins. We performed the first comprehensive screening on AAAs in Asari Radix et Rhizoma (underground part of Asarum heterotropoides Schmidt), the only Aristolochiaceae plant widely used in clinical practice. LC-HRMS revealed 70 trace AAAs using polygonal mass defect filtering and precursor ion list strategies, 38 of which were newly discovered in A. heterotropoides. UHPLC-QTrap-MS/MS was then utilized for quantitative/semiquantitative analysis of 26 abundant compounds. Seventeen AAAs were detected from 91 batches of A. heterotropoides and 20 AAAs from 166 consumable products. For 141 Asari-containing proprietary products, aristolactam I and aristolactam II-glucoside exhibited the widest distribution, present in 98% products. AA IVa was the most abundant, detected in 91%. Notably, 60% of the products contained AA I (0.03-0.79 ppm). The safety was assessed using linear extrapolation, permitted daily exposure, cumulative amount, and the margin of exposure. It is recommended that AA I content be limited to 3 ppm.


Assuntos
Ácidos Aristolóquicos , Medicamentos de Ervas Chinesas , Rizoma , Espectrometria de Massas em Tandem , Medição de Risco
15.
Biologicals ; 41(3): 201-8, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23313102

RESUMO

Residual host cell DNA poses potential safety concerns for cell culture-derived vaccines or other biological products. In addition to the quantity of residual DNA, the size distribution is an important measure for determination of its associated risk factor. We have developed a new method for residual DNA size analysis, based on capillary gel electrophoresis (CGE) technology with sensitive laser induced fluorescence detection (LIF). The performance of this method was optimized through empirical selection of appropriate testing conditions and optimized conditions are presented. Examples are given to demonstrate the successful employment of this method for residual DNA size analysis of cell culture-produced vaccine samples.


Assuntos
DNA/análise , Eletroforese Capilar/métodos , Vacinas Virais/biossíntese , Animais , Linhagem Celular , Chlorocebus aethiops , DNA/genética , Fluorescência , Vacinas contra Influenza/biossíntese , Vacinas contra Influenza/genética , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , Vacinas contra Vírus Sincicial Respiratório/biossíntese , Vacinas contra Vírus Sincicial Respiratório/genética , Células Vero , Vacinas Virais/genética
16.
Biologicals ; 41(4): 247-53, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23665302

RESUMO

The cold-adapted (ca) live attenuated influenza vaccine (LAIV) strains are manufactured in embryonated hens' eggs. Recently, a clonal isolate from Madin Darby Canine Kidney (MDCK) cells was derived and characterized to assess its utility as a potential cell substrate for the manufacturing of LAIV [1]. Since MDCK cells are a transformed continuous cell line [2], and low levels of residual cellular components (DNA and protein) are found in the intermediates and final filled vaccine, we sought to characterize the uptake and clearance of MDCK DNA from tissues in order to assess theoretical risks associated with manufacturing LAIV in MDCK cell culture. In order to address this concern, MDCK DNA uptake and clearance studies were performed in Sprague Dawley rats. DNA extracted from MDCK Master Cell Bank (MCB) cells was administered via an intranasal (IN) or intramuscular (IM) route. Tissue distribution and clearance of MDCK DNA were then examined in fourteen selected tissue types at selected time points post-administration using a quantitative PCR assay specific for canine (SINE) DNA. Results from these studies demonstrate that the uptake and clearance of MDCK DNA from tissues vary depending on the route of administration. When DNA was administered intranasally, as compared to intramuscularly, detectable DNA levels were lower at all time points. Thus, the intranasal route of vaccine administration appears to reduce potential risk associated with residual host cell DNA that may be present in cell culture produced final vaccine products.


Assuntos
DNA/farmacocinética , Administração Intranasal , Animais , Galinhas , DNA/efeitos adversos , DNA/química , DNA/isolamento & purificação , DNA/farmacologia , Cães , Vacinas contra Influenza/isolamento & purificação , Vacinas contra Influenza/farmacologia , Injeções Intramusculares , Células Madin Darby de Rim Canino , Ratos , Vacinas Atenuadas/isolamento & purificação , Vacinas Atenuadas/farmacologia
17.
Biomed Chromatogr ; 27(9): 1177-87, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23723086

RESUMO

Ganoderic acid B (GAB), a representative triterpenoid in Ganoderma lucidum, possesses various pharmaceutical effects and has been used as a chemical marker in quality control of G. lucidum and related products. The metabolites of GAB in vivo after its oral administration to rats were investigated by liquid chromatography coupled with electrospray ionization hybrid ion trap and time-of-flight mass spectrometry. A total of 14 metabolites of GAB in rat plasma, bile and various organs were detected and identified by direct comparison with the authentic compounds and their characteristic mass fragmentation patterns. The results showed that oxidization and hydroxylation were the common metabolic pathways for GAB in rats. Moreover, some reduction metabolites of GAB were detected in rat kidney and stomach and glucuronidation only appeared in rat bile. This is the first report on the metabolites of GAB in vivo.


Assuntos
Cromatografia Líquida/métodos , Polissacarídeos/química , Reishi/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Esteróis/química , Animais , Masculino , Redes e Vias Metabólicas , Modelos Moleculares , Polissacarídeos/sangue , Polissacarídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Esteróis/sangue , Esteróis/metabolismo
18.
Dalton Trans ; 52(32): 11120-11129, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37494113

RESUMO

By using 2-(9-phenanthryl)pyridine (phpyr) and its derivatives as cyclometalated ligands, we synthesized a set of isomeric red-emitting complexes Ir(phpyr-R)2tmd (R = -H, -CF3, -F and -CH3, tmd = 2,2,6,6-tetramethylheptane-3,5-dione) with different coordinated modes, including bis-five-membered and five- + six-membered Ir-(C^N) ring chelating modes. The latter are the first examples of hetero-coordinated Ir(C^N)2(L^X)-type complexes containing both five- and six-membered Ir-(C^N) metallocycles. Their coordination geometries were distinctly determined using X-ray crystallographic analysis. Compared to typical bis-five-membered ring-chelated complexes, these novel hetero-coordinated isomers show bathochromic emission and lower quantum yields. On careful analysis of their electrochemical behavior and DFT calculations, it has been found that the regulatory effects of the solitary six-membered metallocycles in Ir(phpyr-R)2tmd could not only stabilize the LUMO but also destabilize the HOMO, leading to a narrower energy gap. More importantly, DFT calculations of the relative energies of these isomeric complexes demonstrated that bis-five-membered and five- + six-membered chelating modes are more stable compared to bis-six-membered rings, consistent with experiments. This work provides guidance for the structural design of Ir(C^N)2(L^X)-type complexes.

19.
World J Diabetes ; 14(12): 1793-1802, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38222787

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with periodontitis. Currently, there are few studies proposing predictive models for periodontitis in patients with T2DM. AIM: To determine the factors influencing periodontitis in patients with T2DM by constructing logistic regression and random forest models. METHODS: In this a retrospective study, 300 patients with T2DM who were hospitalized at the First People's Hospital of Wenling from January 2022 to June 2022 were selected for inclusion, and their data were collected from hospital records. We used logistic regression to analyze factors associated with periodontitis in patients with T2DM, and random forest and logistic regression prediction models were established. The prediction efficiency of the models was compared using the area under the receiver operating characteristic curve (AUC). RESULTS: Of 300 patients with T2DM, 224 had periodontitis, with an incidence of 74.67%. Logistic regression analysis showed that age [odds ratio (OR) = 1.047, 95% confidence interval (CI): 1.017-1.078], teeth brushing frequency (OR = 4.303, 95%CI: 2.154-8.599), education level (OR = 0.528, 95%CI: 0.348-0.800), glycosylated hemoglobin (HbA1c) (OR = 2.545, 95%CI: 1.770-3.661), total cholesterol (TC) (OR = 2.872, 95%CI: 1.725-4.781), and triglyceride (TG) (OR = 3.306, 95%CI: 1.019-10.723) influenced the occurrence of periodontitis (P < 0.05). The random forest model showed that the most influential variable was HbA1c followed by age, TC, TG, education level, brushing frequency, and sex. Comparison of the prediction effects of the two models showed that in the training dataset, the AUC of the random forest model was higher than that of the logistic regression model (AUC = 1.000 vs AUC = 0.851; P < 0.05). In the validation dataset, there was no significant difference in AUC between the random forest and logistic regression models (AUC = 0.946 vs AUC = 0.915; P > 0.05). CONCLUSION: Both random forest and logistic regression models have good predictive value and can accurately predict the risk of periodontitis in patients with T2DM.

20.
J Clin Med ; 12(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36902664

RESUMO

BACKGROUND: Although neuromuscular blocker agents (NMBAs) are recommended by guidelines as a treatment for ARDS patients, the efficacy of NMBAs is still controversial. Our study aimed to investigate the association between cisatracurium infusion and the medium- and long-term outcomes of critically ill patients with moderate and severe ARDS. METHODS: We performed a single-center, retrospective study of 485 critically ill adult patients with ARDS based on the Medical Information Mart for Intensive Care III (MIMIC-III) database. Propensity score matching (PSM) was used to match patients receiving NMBA administration with those not receiving NMBAs. The Cox proportional hazards model, Kaplan-Meier method, and subgroup analysis were used to evaluate the relationship between NMBA therapy and 28-day mortality. RESULTS: A total of 485 moderate and severe patients with ARDS were reviewed and 86 pairs of patients were matched after PSM. NMBAs were not associated with reduced 28-day mortality (hazard ratio (HR) 1.44; 95% CI: 0.85~2.46; p = 0.20), 90-day mortality (HR = 1.49; 95% CI: 0.92~2.41; p = 0.10), 1-year mortality (HR = 1.34; 95% CI: 0.86~2.09; p = 0.20), or hospital mortality (HR = 1.34; 95% CI: 0.81~2.24; p = 0.30). However, NMBAs were associated with a prolonged duration of ventilation and the length of ICU stay. CONCLUSIONS: NMBAs were not associated with improved medium- and long-term survival and may result in some adverse clinical outcomes.

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