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1.
BMC Med Inform Decis Mak ; 23(1): 230, 2023 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-37858225

RESUMEN

BACKGROUND: Obstructive sleep apnea (OSA) is a globally prevalent disease with a complex diagnostic method. Severe OSA is associated with multi-system dysfunction. We aimed to develop an interpretable machine learning (ML) model for predicting the risk of severe OSA and analyzing the risk factors based on clinical characteristics and questionnaires. METHODS: This was a retrospective study comprising 1656 subjects who presented and underwent polysomnography (PSG) between 2018 and 2021. A total of 23 variables were included, and after univariate analysis, 15 variables were selected for further preprocessing. Six types of classification models were used to evaluate the ability to predict severe OSA, namely logistic regression (LR), gradient boosting machine (GBM), extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), bootstrapped aggregating (Bagging), and multilayer perceptron (MLP). All models used the area under the receiver operating characteristic curve (AUC) was calculated as the performance metric. We also drew SHapley Additive exPlanations (SHAP) plots to interpret predictive results and to analyze the relative importance of risk factors. An online calculator was developed to estimate the risk of severe OSA in individuals. RESULTS: Among the enrolled subjects, 61.47% (1018/1656) were diagnosed with severe OSA. Multivariate LR analysis showed that 10 of 23 variables were independent risk factors for severe OSA. The GBM model showed the best performance (AUC = 0.857, accuracy = 0.766, sensitivity = 0.798, specificity = 0.734). An online calculator was developed to estimate the risk of severe OSA based on the GBM model. Finally, waist circumference, neck circumference, the Epworth Sleepiness Scale, age, and the Berlin questionnaire were revealed by the SHAP plot as the top five critical variables contributing to the diagnosis of severe OSA. Additionally, two typical cases were analyzed to interpret the contribution of each variable to the outcome prediction in a single patient. CONCLUSIONS: We established six risk prediction models for severe OSA using ML algorithms. Among them, the GBM model performed best. The model facilitates individualized assessment and further clinical strategies for patients with suspected severe OSA. This will help to identify patients with severe OSA as early as possible and ensure their timely treatment. TRIAL REGISTRATION: Retrospectively registered.


Asunto(s)
Apnea Obstructiva del Sueño , Humanos , Adulto , Estudios Retrospectivos , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Curva ROC , Factores de Riesgo , Aprendizaje Automático
2.
BMC Surg ; 23(1): 254, 2023 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-37635206

RESUMEN

BACKGROUND: To investigate the relationship between tongue fat content and severity of obstructive sleep apnea (OSA) and its effects on the efficacy of uvulopalatopharyngoplasty (UPPP) in the Chinese group. METHOD: Fifty-two participants concluded to this study were diagnosed as OSA by performing polysomnography (PSG) then they were divided into moderate group and severe group according to apnea hypopnea index (AHI). All of them were also collected a series of data including age, BMI, height, weight, neck circumference, abdominal circumference, magnetic resonance imaging (MRI) of upper airway and the score of Epworth Sleepiness Scale (ESS) on the morning after they completed PSG. The relationship between tongue fat content and severity of OSA as well as the association between tongue fat content in pre-operation and surgical efficacy were analyzed.Participants underwent UPPP and followed up at 3rd month after surgery, and they were divided into two groups according to the surgical efficacy. RESULTS: There were 7 patients in the moderate OSA group and 45 patients in the severe OSA group. The tongue volume was significantly larger in the severe OSA group than that in the moderate OSA group. There was no difference in tongue fat volume and tongue fat rate between the two groups. There was no association among tongue fat content, AHI, obstructive apnea hypopnea index, obstructive apnea index and Epworth sleepiness scale (all P > 0.05), but tongue fat content was related to the lowest oxygen saturation (r=-0.335, P < 0.05). There was no significantly difference in pre-operative tongue fat content in two different surgical efficacy groups. CONCLUSIONS: This study didn't show an association between tongue fat content and the severity of OSA in the Chinese group, but it suggested a negative correlation between tongue fat content and the lowest oxygen saturation (LSaO2). Tongue fat content didn't influence surgical efficacy of UPPP in Chinese OSA patients. TRIAL REGISTRATION: This study didn't report on a clinical trial, it was retrospectively registered.


Asunto(s)
Adiposidad , Pueblos del Este de Asia , Procedimientos Quirúrgicos Otorrinolaringológicos , Apnea Obstructiva del Sueño , Lengua , Humanos , Pueblo Asiatico , Polisomnografía , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/cirugía , Somnolencia , Lengua/anatomía & histología , Lengua/cirugía
3.
Sleep Med ; 103: 106-115, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36774744

RESUMEN

PURPOSE: To explore whether the obstructive sleep apnea (OSA) has an impact on thyroid function in patients. METHOD: The data of 853 patients were retrospectively collected from the Second Affiliated Hospital of Xi'an Jiaotong University in recent ten years. All the objects were divided into the control group, mild-moderate and severe OSA groups according to the result of polysomnography. RESULTS: In the non-elderly population (age <60), there were significant differences in serum free triiodothyronine (FT3) and total triiodothyronine (TT3) between the mild-moderate and severe OSA groups (all p < 0.05). And there were differences in serum total thyroxine, anti-thyroid peroxidase, and antithyroglobulin between the control and mild-moderate OSA groups (all p < 0.05). Moreover, FT3 was associated with age (OR = 0.98, p < 0.05) and apnea-hypopnea index (OR = 1.01, p < 0.05). The occurrence of thyroid nodules was associated with average transcutaneous oxygen saturation (Mean SaO2) (OR = 0.97, p < 0.05). In the elderly (age ≥60), there was no difference in FT3 and TT3 between the mild-moderate and severe OSA. While the occurrence of thyroid nodules was also associated with Mean SaO2 (OR = 0.90, p < 0.05). CONCLUSION: In the non-elderly population, the progress of OSA may promote the increase in thyroid hormone (especially FT3) levels, while in the elderly population not. In the whole age population, Mean SaO 2 is associated with the occurrence of thyroid nodules. Future research on the relationship between OSA and thyroid function, and age stratification is necessary.


Asunto(s)
Apnea Obstructiva del Sueño , Nódulo Tiroideo , Humanos , Persona de Mediana Edad , Triyodotironina , Estudios Retrospectivos , Nódulo Tiroideo/complicaciones , Polisomnografía
4.
Food Res Int ; 163: 112255, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36596166

RESUMEN

Polysaccharides as a functional prebiotic have numerous activities such as regulating intestinal microorganisms and polysaccharide is one of the functional active components in tea has been known. In this study, we aimed to investigate the physicochemical characteristics of polysaccharides from four kinds of Tibetan teas at simulated digestion stages and the effect on the microbiota of fecal fermentation stages in vitro. The results revealed that Tibetan tea polysaccharides were partially digested during digestion. Additionally, during in vitro fecal microbial fermentation, Tibetan tea polysaccharides can promote the growth of some beneficial bacteria such as Bifidobacterium, Prevotella and Phascolarctobacterium to change the composition of intestinal microorganisms and promote the production of short-chain fatty acids (SCFAs). Finally, a strong correlation was found between the production of SCFAs and microorganisms including Bacteroides, Bifidobacterium and Lachnoclostridium. These results suggest that Tibetan tea polysaccharides could be developed as a prebiotic to regulate human gut microbiota.


Asunto(s)
Digestión , Polisacáridos , Humanos , Fermentación , Tibet , Prebióticos , Ácidos Grasos Volátiles ,
5.
Chem Asian J ; 18(2): e202201117, 2023 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-36458644

RESUMEN

The cascade sequential reaction of α-keto acids, 1-iodoalkynes, and alkyl halides are reported herein to synthesize tetra-substituted vinyl iodides. It represents an efficient protocol to access a diverse range of tetra-substituted vinyl iodides starting from simple materials in a one-pot fashion, featuring mild reaction conditions, ease of operation, and broad substrate scope.


Asunto(s)
Yoduros , Elementos de Transición , Cetoácidos , Catálisis , Compuestos de Vinilo
6.
Food Chem ; 405(Pt A): 134358, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36370574

RESUMEN

In this study, we investigated the effects of six different cooking methods on the nutrient composition, subsequent bioaccessibility, and biological activities of Boletus auripes using in vitro digestion. The cooking methods used included steaming, boiling, microwaving, stir-frying, frying, and roasting. The results indicated that the degree of protein hydrolysis and amino acid bioaccessibility were lowest during frying, while the opposite was true for microwaving. The fatty acid composition associated with cooking methods changed after digestion, especially linoleic acid, which significantly decreased (e.g., 53.34% to 21.32%, boiled). Mineral bioaccessibility varied by species and cooking method, with the lowest Fe (13.33%) and highest Mg (91.43%) in boiling. Cooking promoted carbohydrates release heavily, but not digestion, such as the superior bioaccessibility (17.21%) and inferior digestibility (6.23%) in roasting. Microwaving, with the lowest antioxidant activity, possessed notable hypoglycemic activity. The above study lays the foundation for choosing the appropriate cooking methods for B. auripes.


Asunto(s)
Basidiomycota , Culinaria , Culinaria/métodos , Nutrientes , Antioxidantes
7.
Front Cardiovasc Med ; 9: 1042996, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36545020

RESUMEN

Background: Obstructive sleep apnea (OSA) is a globally prevalent disease closely associated with hypertension. To date, no predictive model for OSA-related hypertension has been established. We aimed to use machine learning (ML) to construct a model to analyze risk factors and predict OSA-related hypertension. Materials and methods: We retrospectively collected the clinical data of OSA patients diagnosed by polysomnography from October 2019 to December 2021 and randomly divided them into training and validation sets. A total of 1,493 OSA patients with 27 variables were included. Independent risk factors for the risk of OSA-related hypertension were screened by the multifactorial logistic regression models. Six ML algorithms, including the logistic regression (LR), the gradient boosting machine (GBM), the extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), bootstrapped aggregating (Bagging), and the multilayer perceptron (MLP), were used to develop the model on the training set. The validation set was used to tune the model hyperparameters to determine the final prediction model. We compared the accuracy and discrimination of the models to identify the best machine learning algorithm for predicting OSA-related hypertension. In addition, a web-based tool was developed to promote its clinical application. We used permutation importance and Shapley additive explanations (SHAP) to determine the importance of the selected features and interpret the ML models. Results: A total of 18 variables were selected for the models. The GBM model achieved the most extraordinary discriminatory ability (area under the receiver operating characteristic curve = 0.873, accuracy = 0.885, sensitivity = 0.713), and on the basis of this model, an online tool was built to help clinicians optimize OSA-related hypertension patient diagnosis. Finally, age, family history of hypertension, minimum arterial oxygen saturation, body mass index, and percentage of time of SaO2 < 90% were revealed by the SHAP method as the top five critical variables contributing to the diagnosis of OSA-related hypertension. Conclusion: We established a risk prediction model for OSA-related hypertension patients using the ML method and demonstrated that among the six ML models, the gradient boosting machine model performs best. This prediction model could help to identify high-risk OSA-related hypertension patients, provide early and individualized diagnoses and treatment plans, protect patients from the serious consequences of OSA-related hypertension, and minimize the burden on society.

8.
Micromachines (Basel) ; 13(9)2022 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-36144144

RESUMEN

In recent years, the emergence of COVID-19 and other epidemics caused by RNA(ribonucleic acid)-type genetic viruses has aroused the close attention of governments around the world on emergency response to public safety and health emergencies. In this paper, an electrodeless biosensing detection chip for RNA virus medical detection is designed using quartz crystal microbalance technology and local surface plasmon resonance technology. The plasmonic resonance characteristic in the nanostructures of gold nanorods-quartz substrates with different parameters and the surface potential distribution of the quartz crystal microbalance sensing chip were studied by COMSOL finite element simulation software. The results show that the arrangement structure and spacing of gold nanorod dimers greatly affect the local surface plasmon resonance of nanorods, which in turn affects the detection results of biomolecules. Moreover, high concentrations of "hot spots" are distributed between both ends and the gap of the gold nanorod dimer, which reflects the strong hybridization of the multiple resonance modes of the nanoparticles. In addition, by simulating and calculating the surface potential distribution of the electrode area and non-electrode area of the biosensor chip, it was found that the biosensor chip with these two areas can enhance the piezoelectric effect of the quartz chip. Under the same simulation conditions, the biochip with a completely electrodeless structure showed a better sensing performance. The sensor chip combining QCM and LSPR can reduce the influence of the metal electrode on the quartz wafer to improve the sensitivity and accuracy of detection. Considering the significant influence of the gold nanorod dimer plasma resonance mode and the significant advantages of the electrodeless biosensor chip, an electrodeless biosensor combining these two technologies is proposed for RNA virus detection and screening, which has potential applications in biomolecular measurement and other related fields.

9.
RSC Adv ; 12(37): 24237-24241, 2022 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-36128547

RESUMEN

Annulation reaction of α-keto acids with cyclic or acyclic aliphatic ketones is reported herein to divergently access γ-hydroxy-butenolides and γ-alkylidene-butenolides depending on the amount of BF3·Et2O. This protocol features good functional tolerance and ease of operation, to open a route to access butenolides via an annulation and dehydration process.

10.
Perspect ASHA Spec Interest Groups ; 7(3): 728-740, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35875421

RESUMEN

Purpose: This study examined the relationship between judged speech sound distortions and spectral moment metrics in speakers with Class III malocclusion. Methods: A quantitative online survey was distributed to 30 speech specialists (clinicians and/or students) and 100 lay listeners to judge the clarity of the sounds /s/, /ʃ/, /t/ and /k/ using a visual analog scale (VAS) from recordings of 11 Class III (underbite) Dentofacial Disharmony (DFD) patients and eight Class I controls. Patients and controls were grouped according to high, moderate, and low /s/-/ʃ/ first spectral moment differences. A linear mixed model was used to analyze the data. Results: VAS scale ratings increased as a function of decreasing spectral contrast for both groups of listeners. VAS ratings of speech specialists were more homogenous than lay listeners, and speech specialists rated distortions as less severe than lay listeners. Conclusions: Recordings of Class III DFD patients with low /s/-/ʃ/ first spectral moment differences were scored by listeners as having increased VAS scale ratings, indicative of more significant perceived speech-sound distortions. Spectral moment analysis appears to be a promising approach for characterizing speech of DFD patients and other craniofacial disorders.

11.
Front Pediatr ; 10: 1027894, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36683819

RESUMEN

Background: As an important neuroprotective factor, the brain-derived neurotrophic factor (BDNF) may have a key role in cognitive impairment in children with sleep-disordered breathing (SDB). The main aim of this study was to compare the levels of BDNF and tyrosine kinase receptor B (TrkB) in normal children and those with obstructive sleep apnea (OSA) and primary snoring (PS) and to explore a possible link between BDNF/TrkB, inflammation, and SDB with cognitive impairment in children. Methods: A total of 44 OSA children and 35 PS children who completed polysomnography between October 2017 and October 2019 were enrolled. At the same time, 40 healthy children during the same period were included as a control. Enzyme-linked immunosorbent assay was used to measure serum indices of BDNF, TrkB, interleukin-1beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Correlation and pooled analyses were performed between the cognitive scores and four serological indicators. Logistic regression was used to analyze the risk factors for cognitive impairment. Results: Significant differences were found in serum BDNF, TrkB, IL-1ß, and TNF-α between the three groups (all P < 0.01). The serum BDNF and TrkB in the OSA and PS groups were lower than those in the control group, whereas the serum IL-1ß and TNF-α were higher than those in the control group (all P < 0.05). Moreover, among these four indices, the strongest correlation was found between BDNF and the Chinese Wechsler Intelligence Scale (all P < 0.05). Logistic regression analysis revealed a correlation between OSA status, TrkB, and course of mouth breathing and cognitive status. Conclusion: The levels of serum BDNF and TrkB were related to cognitive impairment in children with SDB. Also, BDNF and TrkB could be used as noninvasive and objective candidate markers and predictive indices of cognitive impairment in children with SDB.

12.
Org Biomol Chem ; 19(38): 8295-8300, 2021 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-34519742

RESUMEN

The electrochemical sulfonylation of enamides with sodium sulfinates was developed in an undivided cell in constant current mode, leading to the formation of ß-amidovinyl sulfones in moderate to good yields. The catalyst-, electrolyte- and oxidant-free protocol features good functional group tolerance and employs electric current as a green oxidant. Mechanistic insights into the reaction indicate that the reaction may proceed via a radical mechanism.


Asunto(s)
Sodio , Sulfonas , Catálisis , Iones , Oxidantes
13.
Curr Drug Metab ; 21(13): 1060-1067, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33198612

RESUMEN

BACKGROUND: Leonurine (Leo), a promising antilipemic agent that has been approved for clinical trials, is extensively metabolized into bioactive Leonurine-10-O-ß-glucuronide (L-10-G) vivo. OBJECTIVE: To explore the effects of breast cancer resistance protein (Bcrp) and multidrug resistance protein 2 (Mrp2) on the disposition of L-10-G. METHODS: The pharmacokinetics, tissue distribution and intestinal perfusion of Leo were studied by using efflux transporter gene knockout mouse models. The enzyme kinetics via liver and intestinal microsomes were also examined. RESULTS: After intravenous injection with Leo, the AUC0-∞ values of L-10-G in Bcrp1-/- and Mrp2-/- mice were 1.55-fold and 16.80-fold higher, respectively, than those in wild-type FVB mice (P < 0.05). After oral administration, the AUC0-∞ value of L-10-G showed a 2.82-fold increase in Mrp2-/- mice compared with wild-type FVB mice (P < 0.05). After gavage with Leo for 10 and 25 min, the bile accumulation of L-10-G in Mrp2-/- mice was 3-fold and 22-fold lower, respectively, than that in wild-type FVB mice (P < 0.05). Besides, the intestinal excreted amount of L-10-G showed 2.22-fold and 2.68-fold decrease in Bcrp1-/- and Mrp2-/- mice, respectively, compared with that in wild-type FVB mice (P < 0.05). The clearance of L-10-G decreased in liver microsomes and increased in intestinal microsomes of Bcrp1-/- and Mrp2-/- mice compared to the wild-type FVB mice (P < 0.05). CONCLUSION: Both Bcrp and Mrp2 are involved in the disposition of L-10-G, and Mrp2 exhibits a superior influence.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Ácido Gálico/análogos & derivados , Hipolipemiantes/farmacocinética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Animales , Área Bajo la Curva , Ácido Gálico/administración & dosificación , Ácido Gálico/farmacocinética , Glucurónidos/metabolismo , Hipolipemiantes/administración & dosificación , Masculino , Ratones , Ratones Noqueados , Microsomas Hepáticos , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Distribución Tisular
14.
Toxicol Appl Pharmacol ; 409: 115332, 2020 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-33171190

RESUMEN

Mesaconitine (MA) and hypaconitine (HA) are the main bioactive/toxic alkaloids of Aconitum carmichaelii Debx, and MDR1, BCRP and MRP2 are involved in their efflux in vitro. This study aimed to explore the effects of Mdr1a, Bcrp and Mrp2 on the efficacy/toxicity of MA and HA by using efflux transporter gene knockout mouse models. The analgesic and anti-inflammatory effects, neurotoxicity/cardiotoxicity, and pharmacokinetic profiles of MA and HA were studied. Compared to wild-type mice, the analgesic effects of MA or HA were significantly enhanced in Mdr1a--/-, Bcrp1-/- and Mrp2-/- mice, and the anti-inflammatory effects notably increased in Bcrp1-/- and Mrp2-/- mice. Compared to wild-type mice, Mdr1a-/-, Bcrp1-/- and Mrp2-/- mice suffered from severe karyopyknosis and edema in the brain after MA or HA treatment. Meanwhile, significant arrhythmia appeared, and the heart rate and RR-interval were greatly altered in Mdr1a-/-, Bcrp1-/- and Mrp2-/- mice. Additionally, obvious disorder of cardiomyocytes were observed, and the CK and cTnT (indicators of heart injury) levels were greatly enhanced in efflux transporter gene knockout mice. The brain levels of MA and HA were markedly increased in Mdr1a-/-, Bcrp1-/- and Mrp2-/- mice, and the heart levels of MA and HA enhanced greatly in Mdr1a-/- mice. The MRT0-t values of MA and HA were remarkably enhanced in most efflux transporter gene knockout mice. In conclusion, Mdr1a, Bcrp and Mrp2 were all involved in regulating the efficacy/toxicity of MA and HA by altering their tissue accumulation and in vivo residence. Among the three efflux transporters, Mdr1a had a superior regulatory effect.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Aconitina/análogos & derivados , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Aconitina/farmacología , Alcaloides/farmacología , Animales , Transporte Biológico/efectos de los fármacos , Transporte Biológico/genética , Encéfalo/efectos de los fármacos , Técnicas de Inactivación de Genes , Masculino , Ratones , Ratones Noqueados , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos
15.
Drug Metab Dispos ; 47(3): 203-214, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30602435

RESUMEN

Esculetin (ET)-7-O-glucuronide (ET-G) and 4-methylesculetin (4-ME)-7-O-glucuronide (4-ME-G) are the main glucuronide of ET and 4-ME, respectively. The disposition mediated by efflux transporters for glucuronide has significant influence on the pharmacokinetic profile and efficacy of bioactive compounds. In the current study, transporter gene knockout mice and Caco-2 cells were used to explore the effects of breast cancer resistance protein (BCRP) and multidrug resistance-associated protein 2 (MRP2) on the disposition of ET-G and 4-ME-G. After oral or i.v. administration of ET and 4-ME, the area under the plasma concentration-time curve from time 0 to the last data point or infinity values of ET, 4-ME, and their glucuronides (ET-G and 4-ME-G) were remarkably and significantly increased in most Bcrp1-/- and Mrp2-/- mice compared with those in wild-type FVB mice (P < 0.05). These results were accompanied with a significant increase of maximum plasma concentration values (P < 0.05). In Caco-2 monolayers, the efflux and clearance rates of ET-G and 4-ME-G were markedly reduced by the BCRP inhibitor Ko143 and MRP2 inhibitor MK571 on the apical side (P < 0.05). In an intestinal perfusion study, the excretion of ET-G was significantly decreased in perfusate and increased in plasma in Bcrp1-/- mice compared with those in wild-type FVB mice (P < 0.05). The 4-ME-G concentration was also decreased in the bile in transporter gene knockout mice. ET and 4-ME showed good permeability in both Caco-2 monolayers [apparent permeability (Papp ) ≥ 0.59 × 10-5 cm/s] and duodenum (Papp ≥ 1.81). In conclusion, BCRP and MRP2 are involved in excreting ET-G and 4-ME-G. ET and 4-ME are most likely absorbed via passive diffusion in the intestines.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteínas de Neoplasias/metabolismo , Umbeliferonas/farmacocinética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/antagonistas & inhibidores , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Animales , Área Bajo la Curva , Células CACO-2 , Dicetopiperazinas/farmacología , Glucurónidos/metabolismo , Glucuronosiltransferasa/metabolismo , Eliminación Hepatobiliar/efectos de los fármacos , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Humanos , Absorción Intestinal , Mucosa Intestinal/metabolismo , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Ratones , Ratones Noqueados , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/antagonistas & inhibidores , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas de Neoplasias/antagonistas & inhibidores , Perfusión , Propionatos/farmacología , Quinolinas/farmacología , Umbeliferonas/metabolismo
16.
Chemosphere ; 217: 298-307, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30419384

RESUMEN

Increasing PAHs pollution is creating more complex urban pollution system. However, the availability of sufficient monitoring activities for PAHs in multicompartment and corresponding multi-interface migration processes is still not well understood. In this study, a Level III steady state fugacity model was validated to evaluate the detailed local variations, and mass fluxes of PAHs in various environmental compartments (i.e., air, soil, sediment, water, vegetation and organic film). This model was applied to a region of Shanghai in 2012 based on a large number of measured data and brings model predictions in 2020. The model results indicate that most of the simulated concentrations agreed with the observed values within one order of magnitude with a tendency of underestimation for vegetation. Direct emission is the main input pathway of PAHs entering the atmosphere, whereas advection is the main outward flow from Shanghai. Organic film was achieved the highest concentration of PAHs compared to other compartments up to 58.17 g/m3. The soil and sediment served as the greatest sinks of PAHs and have the longest retention time (2421.95-78642.09 h). Importantly, a decreasing trend of PAHs was observed in multimedia from 2012 to 2020 and the transfer flux from the air to vegetation to soil was the dominant pathways of BaP intermedia circulation processes. A sensitivity analysis showed that temperature was the most influential parameter, especially for Phe. A Monte Carlo simulation emphasized heavier PAHs were overpredicted in film and sediment, but lighter PAHs in air and water were generally underestimated.


Asunto(s)
Contaminantes Ambientales/análisis , Modelos Teóricos , Hidrocarburos Policíclicos Aromáticos/análisis , Urbanización , China , Método de Montecarlo , Temperatura
17.
Mol Pharm ; 15(12): 5602-5614, 2018 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-30376625

RESUMEN

Glucuronidation is a major process of drug metabolism and elimination that generally governs drug efficacy and toxicity. Publications have demonstrated that efflux transporters control intracellular glucuronidation metabolism. However, it is still unclear whether and how efflux transporters interact with UDP-glucuronosyltransferases (UGTs) in subcellular organelles. In this study, kaempferol, a model fluorescent flavonoid, was used to investigate the interplay of glucuronidation with transport at the subcellular level. Human recombinant UGTs and microsomes were utilized to characterize the in vitro glucuronidation kinetics of kaempferol. The inhibition of UGTs and efflux transporters on the subcellular disposition of kaempferol were determined visually and quantitatively in Caco-2/TC7 cells. The knockout of transporters on the subcellular accumulation of kaempferol in liver and intestine were evaluated visually. ROS and Nrf2 were assayed to evaluate the pharmacological activities of kaempferol. The results showed that UGT1A9 is the primary enzyme responsible for kaempferol glucuronidation. Visual and quantitative data showed that the UGT1A9 inhibitor carvacrol caused a significant rise in subcellular aglycone and reduction in subcellular glucuronides of kaempferol. The inhibition and knockout of transporters, such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins (MRPs), exhibited a marked increase in subcellular kaempferol and decrease in its subcellular glucuronides. Correspondingly, inhibition of UGT1A9 and transporters led to increased kaempferol and, consequently, a significantly enhanced ROS scavenging efficiency and nuclear translocation of Nrf2. In conclusion, the interplay of efflux transporters (P-gp, BCRP, and MRPs) and UGTs govern the subcellular exposure and corresponding pharmacological activity of kaempferol.


Asunto(s)
Glucurónidos/metabolismo , Glucuronosiltransferasa/metabolismo , Quempferoles/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Animales , Células CACO-2 , Cimenos , Glucuronosiltransferasa/antagonistas & inhibidores , Humanos , Intestinos/citología , Proteínas de Transporte de Membrana/genética , Ratones Noqueados , Microsomas/metabolismo , Monoterpenos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , UDP Glucuronosiltransferasa 1A9
18.
Pain Physician ; 21(2): E157-E165, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29565958

RESUMEN

BACKGROUND: The extraforaminal ligaments between the L1-L5 lumbar spinal nerves and the tissues surrounding the intervertebral foramina (IVF) have been well studied. However, little research has been performed to describe the local anatomy of the entrance zones at the L1-L5 level. Detailed anatomic studies of the intraforaminal ligaments (IFLs) in the entrance zones at the L1-L5 levels have not been performed. OBJECTIVES: The objective of this study is to identify and describe the IFLs in the entrance zones of the L1-L5 IVF and to determine their possible clinical significance. STUDY DESIGN: A dissection-based study of 10 fresh-frozen human cadavers. SETTING: Guangdong Provincial Key Laboratory of Medical Biomechanics in Anatomy Department of Southern Medical University. METHODS: Eighty L1-L5 IVF from 10 fresh cadavers were studied, and the IFLs in the entrance zones were identified. The quantities, morphologies, origins, insertions, and spatial orientations of the IFLs in the entrance zones of the L1-L5 IVF were observed. The lengths, widths, diameters, and thicknesses of the ligaments were measured using a vernier caliper. Ten intraforaminal radiating ligaments were removed for histological examination. RESULTS: A total of 197 ligaments were identified in the entrance zones of the 80 L1-L5 IVF, including 191 (96.95%) radiating ligaments and 6 (3.05%) transforaminal ligaments. The thickest ligaments were observed at the L3-L4 IVF. The lengths of the ligaments varied from 0.59 to 11.92 mm. There were 66 (33.50%) ligaments in the superior aspect of the entrance zone of the IVF, 58 (29.44%) ligaments at the anterior aspect, 43 (21.83%) ligaments at the posterior aspect, and 30 (15.23%) ligaments at the inferior aspect. The morphologies of the IFLs were divided into 2 types: the strap type and the trabs type. Histological examination of the meningovertebral ligaments revealed fibrous connective tissue. LIMITATIONS: The major limitation of this study is the lack of actual clinical data from live patients. In addition, future medical biomechanics experiments are expected to contribute more objective data on the strength of the IFLs. CONCLUSIONS: In the lumbar spine, IFLs are common structures in the entrance zones of the L1-L5 IVF, and radiating ligaments are more likely to be present. KEY WORDS: Clinical Anatomy, microdissection, intraforaminal ligament, the entrance zone, L1-L5 intervertebral foramen, endoscopic spinal adhesiolysis, sacral hiatus, cerebrospinal fluid leakage, dural laceration.


Asunto(s)
Ligamentos/anatomía & histología , Región Lumbosacra/anatomía & histología , Adulto , Cadáver , Femenino , Humanos , Vértebras Lumbares , Masculino , Persona de Mediana Edad
19.
Mitochondrial DNA A DNA Mapp Seq Anal ; 28(3): 309-310, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-26713397

RESUMEN

Acer morrisonense (Aceraceae) is an important forest tree species and is endemic to Taiwan area. In this study, we determined the complete nucleotide sequence of A. morrisonense chloroplast genome (cpDNA) by using next-generation sequencing. The cpDNA was 157 197 bp in size, contained a pair of 26 728 bp inverted repeat (IR) regions, which were separated by a large single copy region (LSC) and a small single copy (SSC) region of 85 655 and 18 086 bp, respectively. The cpDNA contained 134 genes, including 86 protein-coding genes (78 PCG species), 8 ribosomal RNA genes (four rRNA species), and 40 transfer RNA genes (31 tRNA species). The most of gene species occur as a single copy, while 21 gene species occur in double copies. The overall AT content of A. morrisonense chloroplast genome were 62.2%, while the corresponding values of the LSC, SSC, and IR regions were 64.0%, 67.9%, and 57.3%, respectively. The phylogenetic analysis suggested that the cpDNA of A. morrisonense is closely related to that of congeneric A. buergerianum subsp. ningpoense.


Asunto(s)
Aceraceae/genética , Genoma del Cloroplasto/genética , Genoma Mitocondrial/genética , Filogenia , ARN Ribosómico/genética
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