Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
Mais filtros

Medicinas Complementares
País/Região como assunto
Intervalo de ano de publicação
1.
Phytomedicine ; 129: 155559, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38579642

RESUMO

BACKGROUND: Osteoclast plays an important role in maintaining the balance between bone anabolism and bone catabolism. The abnormality of osteoclast is closely related to osteolytic bone diseases such as osteoporosis, rheumatoid arthritis and tumor bone metastasis. PURPOSE: We aim to search for natural compound that may suppress osteoclast formation and function. STUDY DESIGN: In this study, we assessed the impact of Dauricine (Dau) on the formation and function of osteoclasts in vitro, as well as its potential in preventing bone loss in an ovariectomy mouse model in vivo. METHODS: Multiple in vitro experiments were carried out, including osteoclastogenesis, podosomal belt formation, bone resorption assay, RNA-sequencing, real-time quantitative PCR, ROS level detection, surface plasmon resonance assay, luciferase assay and western blot. To verify the effect in vivo, an ovariectomized mouse model (OVX model) was constructed, and bone parameters were measured using micro-CT and histology. Furthermore, metabolomics analysis was performed on blood serum samples from the OVX model. RESULTS: In vitro experiments demonstrated that Dau inhibits RANKL-induced osteoclastogenesis, podosomal belt formation, and bone resorption function. RNA-sequencing results revealed that Dau significantly suppresses genes related to osteoclast. Functional enrichment analysis indicated that Dau's inhibition of osteoclasts may be associated with NF-κB signaling pathway and reactive oxygen metabolism pathway. Molecular docking, surface plasmon resonance assay and western blot analysis further confirmed that Dau inhibits RANKL-induced osteoclastogenesis by modulating the ROS/NF-κB/NFATc1 pathway. Moreover, administration of Dau to OVX-induced mice validated its efficacy in treating bone loss disease. CONCLUSION: Dau prevents OVX-induced bone loss by inhibiting osteoclast activity and bone resorption, potentially offering a new approach for preventing and treating metabolic bone diseases such as osteoporosis. This study provides innovative insights into the inhibitory effects of Dau in an in vivo OVX model and elucidates the underlying mechanism.


Assuntos
Benzilisoquinolinas , NF-kappa B , Fatores de Transcrição NFATC , Osteoclastos , Osteogênese , Ovariectomia , Ligante RANK , Espécies Reativas de Oxigênio , Animais , Benzilisoquinolinas/farmacologia , Feminino , Ligante RANK/metabolismo , Camundongos , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Osteogênese/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Modelos Animais de Doenças , Reabsorção Óssea/tratamento farmacológico , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Humanos , Tetra-Hidroisoquinolinas
2.
Chem Biol Interact ; 394: 110968, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38522564

RESUMO

Bone metastases caused by breast cancer pose a major challenge to the successful treatment of breast cancer patients. Many researchers have suggested that herbal medicines are extremely effective at preventing and treating cancer-associated osteolysis. Previous studies have revealed that Morusin (MOR) is cytotoxic to many cancer cells ex vivo. Nevertheless, how MOR contributes to osteolysis induced by breast cancer is still unknown, and the potential mechanism of action against osteolysis is worthy of further study. The protective effect and molecular mechanism of MOR in inhibiting breast cancer cell-induced osteolysis were verified by experiments and network pharmacology. Cell function was assessed by cell proliferation, osteoclast (OC) formation, bone resorption, and phalloidin staining. Tumour growth was examined by micro-CT scanning in vivo. To identify potential MOR treatments, the active ingredient-target pathway of breast cancer was screened using network pharmacology and molecular docking approaches. This study is the first to report that MOR can prevent osteolysis induced by breast cancer cells. Specifically, our results revealed that MOR inhibits RANKL-induced osteoclastogenesis and restrains the proliferation, invasion and migration of MDA-MB-231 breast cells through restraining the PI3K/AKT/MTOR signalling pathway. Notably, MOR prevented bone loss caused by breast cancer cell-induced osteolysis in vivo, indicating that MOR inhibited the development of OCs and the resorption of bone, which are essential for cancer cell-associated bone distraction. This study showed that MOR treatment inhibited osteolysis induced by breast cancer in vivo. MOR inhibited OC differentiation and bone resorption ex vivo and in vivo and might be a potential drug candidate for treating breast cancer-induced osteolysis.


Assuntos
Neoplasias da Mama , Osteólise , Fosfatidilinositol 3-Quinase , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Simulação de Acoplamento Molecular , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteólise/metabolismo , Osteólise/tratamento farmacológico , Osteólise/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
3.
Chemosphere ; 309(Pt 1): 136749, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36209864

RESUMO

Phosphorus (P) availability in highly weathered soils is significantly influenced by the contents of iron (Fe)/aluminum (Al) oxides, clay minerals, and organic matter. With the increasing interest in biofertilizers (e.g. chitosan), it is important to understand how they affect P adsorption profiles on colloids of weathered soils rich in Fe/Al oxides. Thus, the effect of chitosan on the adsorption of P to colloids of hematite, gibbsite, Oxisol, and Ultisol was studied through electrokinetic measurements, spectroscopic analysis, and adsorption edge/isotherm profiles. The presence of chitosan significantly improved the surface positive charge and the decreasing trend of surface positive charge was slower for chitosan-treated colloids compared to the control with increasing pH. At pH 5.0, all the colloids were positively charged, with the oxides containing more positve charges than the soil colloids. At this pH value, the surface coverage capacity of P was 99.1, 61.6, 50.5, and 37.5 mmol kg⁻1 for Oxisol, Ultisol, hematite, and gibbsite, respectively. This suggests that clay minerals in soil colloids were vital in enhancing P adsorption. In the presence of chitosan, the surface coverage capacity of P was increased by 111%, 173%, 647%, and 488% for Oxisol, Ultisol, gibbsite, and hematite, respectively. Drawing inferences from spectroscopic analysis, citric acid desorption profile, and zeta potential analysis, we suggest that chitosan (CH) enhanced P adsorption by promoting the formation of (i) citric acid "undisplaceable" inner-sphere P complexes such as [Colloid-OP-O-CH] and [Colloid-OP-N-CH], (ii) citric acid "displaceable" outer-sphere P complexes such as {[Colloid-O-CH]-OP} and {[Colloid-N-CH]-OP}, and (iii) water "leachable or soluble" P complexes such as {[Colloid-CH]+PO4³â»} and {[Colloid-OP]⁻CH+}. Thus, applying chitosan as a biofertilizer (source of N) along with P in highly weathered soils could improve P availability while reducing P leaching.


Assuntos
Quitosana , Poluentes do Solo , Fosfatos/química , Poluentes do Solo/análise , Argila , Alumínio , Solo/química , Coloides/química , Fósforo , Minerais , Ferro , Óxidos , Ácido Cítrico , Água
4.
J Neural Eng ; 19(5)2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36126643

RESUMO

Objective.Motor imagery-based brain computer interfaces (MI-BCIs) have been widely researched because they do not demand external stimuli and have a high degree of maneuverability. In most scenarios, superabundant selected channels, fixed time windows, and frequency bands would certainly affect the performance of MI-BCIs due to the neurophysiological diversities among different individuals. In this study, we attempt to effectively use the Riemannian geometry of spatial covariance matrix to extract more robust features and thus enhance the decoding efficiency.Approach.First, we utilize a Riemannian distance-based electroencephalography (EEG) channel selection method, which preliminarily reduces the information redundancy in the first stage. Second, we extract discriminative Riemannian tangent space features of EEG signals of selected channels from the most discriminant time-frequency bands to further enhance decoding accuracy for MI-BCIs. Finally, we train a support vector machine model with a linear kernel to classify our extracted discriminative Riemannian features, and evaluate our proposed method using publicly available BCI Competition IV dataset Ⅰ (DS1) and Competition Ⅲ dataset Ⅲa (DS2).Main results.The experimental results show that the average classification accuracy with the selected 16-channel EEG signals of our method is 90.0% and 89.4% in DS1 and DS2 respectively. The average improvements are 20.0% and 21.2% on DS1, 9.4% and 7.2% on DS2 for 8 and 16 selected channels, respectively.Significance.These results show that our proposed method is a promising candidate for the performance improvement of MI-BCIs.


Assuntos
Interfaces Cérebro-Computador , Algoritmos , Eletroencefalografia/métodos , Humanos , Imagens, Psicoterapia , Imaginação/fisiologia , Máquina de Vetores de Suporte
5.
Support Care Cancer ; 30(8): 6995-7003, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35576081

RESUMO

OBJECTIVE: Hypophosphatemia might cause respiratory and heart failure and even death. We aimed to evaluate risk factors for hypophosphatemia and refeeding-related hypophosphatemia in patients requiring parental nutrition (PN). METHODS: This was a single-center, retrospective study. Clinical parameters were obtained from medical records. Serum phosphate (inorganic phosphorus) was measured by photometric analysis. Hypophosphatemia was confirmed when serum phosphate level was less than 0.8 mmol/L (≈2.5 mg/dl). Refeeding related hypophosphatemia was confirmed if serum phosphate level had a decrease of 0.16 mmol/L or more from baseline and if the final assessment was below 0.65 mmol/L. RESULTS: A total number of 655 (426 men and 229 women, aged 62.8 ± 14.8 years) hospitalized patients requiring PN were included in the study, and 60.6% of them were patients with cancer. The average body mass index (BMI) was 21.1 ± 4.1 kg/m2 and the median of serum phosphate was 0.9 mmol/L (quartile range: 0.68 mmol/L, 1.11 mmol/L). The prevalence of hypophosphatemia was 37.6% (246/655). Older age (≥ 65 years vs. < 65 years), lower serum level of pre-albumin (< 160 mg/L vs. ≥ 160 mg/L), calcium (< 2.11 mmol/L vs. ≥ 2.11 mmol/L), and magnesium (< 0.75 mmol/L vs. ≥ 0.75 mmol/L) were associated with high risk of hypophosphatemia by multivariate logistic regression (OR ranged from 1.43 to 3.06, all p < 0.05). Refeeding related hypophosphatemia was 9.5% (16/168). Serum level of calcium at baseline was significantly lower in participants with refeeding related hypophosphatemia than those without it. Total calorie and nitrogen delivered during first week of PN period showed no obvious difference between patients with and without refeeding related hypophosphatemia. CONCLUSIONS: Hypophosphatemia is common (37.6%) in hospitalized patients requiring PN. Monitoring of serum level of phosphorus is necessary to facilitate early treatment of hypophosphatemia.


Assuntos
Cálcio , Hipofosfatemia , Cálcio/uso terapêutico , Feminino , Humanos , Hipofosfatemia/epidemiologia , Hipofosfatemia/etiologia , Masculino , Pais , Fosfatos/uso terapêutico , Fósforo/uso terapêutico , Prevalência , Estudos Retrospectivos
6.
Front Pharmacol ; 13: 803880, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35496311

RESUMO

Osteoporosis is a serious public health problem that results in fragility fractures, especially in postmenopausal women. Because the current therapeutic strategy for osteoporosis has various side effects, a safer and more effective treatment is worth exploring. It is important to examine natural plant extracts during new drug design due to low toxicity. Mogrol is an aglycon of mogroside, which is the active component of Siraitia grosvenorii (Swingle) and exhibits anti-inflammatory, anticancer and neuroprotective effects. Here, we demonstrated that mogrol dose-dependently inhibited osteoclast formation and function. To confirm the mechanism, RNA sequencing (RNA-seq), real-time PCR (RT-PCR), immunofluorescence and Western blotting were performed. The RNA-seq data revealed that mogrol had an effect on genes involved in osteoclastogenesis. Furthermore, RT-PCR indicated that mogrol suppressed osteoclastogenesis-related gene expression, including CTSK, ACP5, MMP9 and DC-STAMP, in RANKL-induced bone marrow macrophages Western blotting demonstrated that mogrol suppressed osteoclast formation by blocking TNF receptor-associated factor 6 (TRAF6)-dependent activation of the mitogen-activated protein kinase nuclear factor-B (NF-κB) signaling pathway, which decreased two vital downstream transcription factors, the nuclear factor of activated T cells calcineurin-dependent 1 (NFATc1) and c-Fos proteins expression. Furthermore, mogrol dramatically reduced bone mass loss in postmenopausal mice. In conclusion, these data showed that mogrol may be a promising procedure for osteoporosis prevention or therapy.

7.
Environ Geochem Health ; 44(11): 4191-4200, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35067762

RESUMO

The consortium of minerals and organic matter notably alters and affects minerals' surface characteristics and nutrients providence. Organic matter such as biochar can modify the availability status of macronutrients like phosphorus (P). Despite some investigation, the adsorption/desorption of P with pure iron (hydr)oxides and the probable mechanisms involved are still unknown. In the present study, the goethite/hematite or goethite-biochar/hematite-biochar complexes were prepared, and a batch experiment with different P concentrations, time spell, pH, and ionic strength is performed to evaluate the sorption characteristics of P. The results of our study suggest that the P adsorption on mineral surface decreased with the increasing pH. Furthermore, the coexistence of biochar and minerals significantly inhibits P adsorption on the minerals surface. The results of Languimner and Freundlich's equations signify that the biochar-minerals complexes have heterogeneous adsorption sites and the presence of biochar reduces P adsorption on minerals surface. Among four biochars including peanut straw biochar (PC (B1)), rice straw biochar (RC (B2)), canola straw biochar (CC (B3)), and soybean straw biochar (SC (B4)), PC was more effective than other biochars to inhibit P adsorption on minerals surfaces.


Assuntos
Fosfatos , Solo , Solo/química , Carvão Vegetal/química , Minerais/química , Adsorção , Fósforo , Ferro , Óxidos
8.
Pharm Biol ; 60(1): 1-8, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34860644

RESUMO

CONTEXT: As an inhibitor cytochrome P450 family 2 subfamily C polypeptide 8 (CYP2C8), quercetin is a naturally occurring flavonoid with its glycosides consumed at least 100 mg per day in food. However, it is still unknown whether quercetin and selexipag interact. OBJECTIVE: The study investigated the effect of quercetin on the pharmacokinetics of selexipag and ACT-333679 in beagles. MATERIALS AND METHODS: The ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate the pharmacokinetics of orally administered selexipag (2 mg/kg) with and without quercetin (2 mg/kg/day for 7 days) pre-treatment in beagles. The effect of quercetin on the pharmacokinetics of selexipag and its potential mechanism was studied through the pharmacokinetic parameters. RESULTS: The assay method was validated for selexipag and ACT-333679, and the lower limit of quantification for both was 1 ng/mL. The recovery and the matrix effect of selexipag were 84.5-91.58% and 94.98-99.67%, while for ACT-333679 were 81.21-93.90% and 93.17-99.23%. The UPLC-MS/MS method was sensitive, accurate and precise, and had been applied to the herb-drug interaction study of quercetin with selexipag and ACT-333679. Treatment with quercetin led to an increased in Cmax and AUC0-t of selexipag by about 43.08% and 26.92%, respectively. While the ACT-333679 was about 11.11% and 18.87%, respectively. DISCUSSION AND CONCLUSION: The study indicated that quercetin could inhibit the metabolism of selexipag and ACT-333679 when co-administration. Therefore, the clinical dose of selexipag should be used with caution when co-administered with foods high in quercetin.


Assuntos
Acetamidas/farmacocinética , Acetatos/farmacocinética , Inibidores do Citocromo P-450 CYP2C8/farmacologia , Pirazinas/farmacocinética , Quercetina/farmacologia , Animais , Anti-Hipertensivos/farmacocinética , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Cães , Feminino , Interações Ervas-Drogas , Masculino , Espectrometria de Massas em Tandem
9.
Artigo em Chinês | WPRIM | ID: wpr-935774

RESUMO

Objective: To provide scientific evidence for early lung cancer screening, to analyze the incidence of pulmonary nodules among petroleum company staffs in Sichuan-Chongqing Area. Methods: In January 2021 , 6002 petroleum company staffs in Sichuan-Chongqing Area which scanned by low-dose spiral computed tomography (LDCT) of chest in medical examination center in 2020 were retrospectively collected as objects. Their imaging and clinical data were collected. χ(2) test was used to analyze the differences in the detection rates of lung nodules and suspected lung cancer nodules among workers in petroleum company staffs of different genders, ages and types of work. Results: Among the 6002 objects, 3853 (64.2%) were male and 2149 (35.8%) were female, with an average age of (47.25±12.13) years old. A total of 431 cases (7.2%) of pulmonary nodules and 57 cases (0.9%) of suspected lung cancer nodules were detected. 45 cases were followed up with surgical treatment, and 41 cases (91.1%) of lung cancer were diagnosed by postoperative pathology. There were significant differences in the detection rates of pulmonary nodules and suspected lung cancer nodules between different age groups (χ(2)=51.23, 18.81 , P<0.001). The detection rates of pulmonary nodules in the age groups 51-60 years old and ≥61 years old were higher than those in the age groups≤40 years old and 41-50 years old (P<0.05). The detection rate of suspected lung cancer nodules in the age group≥ 61 years old was higher than those in the age groups≤40 years old, 41-50 years old and 51-60 years old (P< 0.05) . And the detection rate of suspected lung cancer pulmonary nodules in oil workers was higher than that of ordinary workers (P<0.05) . Among female objects, the detection rate of pulmonary nodules in oil workers was higher than that in ordinary workers (χ(2)=8.09, P=0.004) . The detection rate of pulmonary nodules in oil workers aged ≥61 years old was higher than ordinary workers (χ(2)=37.94, P<0.001) . Among male objects, the detection rate of suspected lung cancer pulmonary nodules in oil workers was higher than that in ordinary workers (χ(2)=8.42, P=0.004) . The detection rates of suspected lung cancer pulmonary nodules in oil workers aged 51-60 years old and ≥61 years old groups were higher than those of ordinary workers (χ(2)=4.70, 8.74; P=0.030, 0.003) . Conclusion: LDCT is suitable for early lung cancer screening for petroleum company staffs. During the clinical screening process, LDCT should be used as a routine physical examination item for petroleum workers older than 51 years old.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Programas de Rastreamento/métodos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Petróleo , Estudos Retrospectivos , Tomografia Computadorizada Espiral
10.
Huan Jing Ke Xue ; 42(10): 4897-4907, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581133

RESUMO

This study used 21 rock samples and 193 sets of paddy soil and rice grain samples collected form Baiwang Town, an area of clastic sedimentary rocks in Guangxi, China, to evaluate the potential for selenium-rich agriculture. We analyzed the concentrations of selenium and heavy metals in the soil and rice samples, and discuss the influencing factors by means of statistics and correlation analysis. The results showed that the selenium-rich rate of paddy soil and rice grain in Baiwang Town were 67.4% and 64.8%, respectively, but the content of cadmium in the selenium-rich soil samples was generally higher than the baseline value for China and the background value for Guangxi. In comparison to the screening value of soil pollution risk for agricultural land(GB 15618-2018), the over-standard rate of cadmium was 46.1%, while the over-standard rates of other heavy metals were negligible. The comparison shows that the selenium-rich rate of rice was 61.1% in the southern area of Baiwang Town with a negligible heavy metal content, and the advantages of green selenium-rich rice planting were clear. The correlation analysis showed that secondary enrichment was the main form of selenium enrichment in the study area. The soil pH and texture of the root-zone soil also affected the selenium content of the soil. The selenium content of rice seeds was mainly affected by the selenium content, active selenium content, pH, and aluminum oxide content of the root-zone soil. The risk assessment showed that the level of dietary exposure to cadmium is generally within safe limits, but it is still necessary to strengthen the monitoring of cadmium in rice and control cadmium pollution to reduce the levels of dietary exposure, especially in the central region of Baiwang Town.


Assuntos
Metais Pesados , Oryza , Selênio , Poluentes do Solo , Cádmio/análise , China , Metais Pesados/análise , Solo , Poluentes do Solo/análise
11.
Pharm Biol ; 59(1): 1133-1138, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34410882

RESUMO

CONTEXT: Ambrisentan is an oral endothelin-receptor antagonist (ERA). However, there is no report on the interaction between ambrisentan and shikonin. OBJECTIVE: To investigate the effect of shikonin on ambrisentan metabolism in vivo and in vitro. MATERIALS AND METHODS: This study developed an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of ambrisentan and (S)-4-hydroxymethyl ambrisentan in rat plasma. Twelve male Sprague-Dawley (SD) rats were divided into two groups (n = 6): the control group and shikonin (20 mg/kg) group. The pharmacokinetics of ambrisentan (2.5 mg/kg) were investigated after 30 min. Additionally, human and rat liver microsomes were used to investigate the herb-drug interaction. RESULTS: The UPLC-MS/MS method was shown to be accurate, precise and reliable, and was successfully applied to the herb-drug interaction study of ambrisentan with shikonin. When co-administrated with 20 mg/kg shikonin, the Cmax and AUC(0-∞) of ambrisentan were significantly increased by 44.96 and 16.65%, respectively (p < 0.05). In addition, there were modest decreases in (S)-4-hydroxymethyl ambrisentan Cmax and AUC(0-∞) in the presence of shikonin (p < 0.05), which indicated that these results were in accordance with the inhibition of shikonin on ambrisentan metabolism. Moreover, enzyme kinetic study indicated that shikonin had an inhibitory effect on human and rat microsomes where the IC50 values of shikonin were 5.865 and 6.358 µM, respectively. CONCLUSIONS: Our study indicated that shikonin could inhibit ambrisentan metabolism. Further studies need to be carried out to verify whether similar interaction truly apply in humans and whether this interaction has clinical significance.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Naftoquinonas/farmacologia , Fenilpropionatos/farmacocinética , Piridazinas/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Área Sob a Curva , Interações Ervas-Drogas , Humanos , Masculino , Microssomos Hepáticos , Fenilpropionatos/sangue , Piridazinas/sangue , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
12.
Front Pharmacol ; 12: 619339, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643050

RESUMO

Warfarin is a widely prescribed anticoagulant but the doses required to attain the optimum therapeutic effect exhibit dramatic inter-individual variability. Pharmacogenomics-guided warfarin dosing has been recommended to improve safety and effectiveness. We analyzed the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes among 120 patients taking warfarin. A new coding variant was identified by sequencing CYP2C9. The novel A > G mutation at nucleotide position 14,277 led to an amino acid substitution of isoleucine with valine at position 213 (I213V). The functional consequence of the variant was subsequently evaluated in vitro. cDNA of the novel variant was constructed by site-directed mutagenesis and the recombinant protein was expressed in vitro using a baculovirus-insect cell expression system. The recombinant protein expression was quantified at apoprotein and holoprotein levels. Its enzymatic activities toward tolbutamide, warfarin and losartan were then assessed. It exhibited changed apparent Km values and increases of 148%, 84% and 67% in the intrinsic clearance of tolbutamide, warfarin and losartan, respectively, compared to wild-type CYP2C9*1, indicating dramatically enhanced in vitro enzymatic activity. Our study suggests that the amino acid at position 213 in wild-type CYP2C9*1 may be important for the enzymatic activity of CYP2C9 toward tolbutamide, warfarin and losartan. In summary, a patient taking high-dose warfarin (6.0 mg/day) in order to achieve the target international normalized ratio was found to have a mutation in the CYP2C9 gene.

13.
J Neural Eng ; 18(2)2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33524961

RESUMO

Objective. Motor imagery (MI) is a mental representation of motor behavior and a widely used pattern in electroencephalogram (EEG) based brain-computer interface (BCI) systems. EEG is known for its non-stationary, non-linear features and sensitivity to artifacts from various sources. This study aimed to design a powerful classifier with a strong generalization capability for MI based BCIs.Approach. In this study, we proposed a cluster decomposing based ensemble learning framework (CDECL) for EEG classification of MI based BCIs. The EEG data was decomposed into sub-data sets with different distributions by clustering decomposition. Then a set of heterogeneous classifiers was trained on each sub-data set for generating a diversified classifier search space. To obtain the optimal classifier combination, the ensemble learning was formulated as a multi-objective optimization problem and a stochastic fractal based binary multi-objective fruit fly optimization algorithm was proposed for solving the ensemble learning problem.Main results.The proposed method was validated on two public EEG datasets (BCI Competition IV datasets IIb and BCI Competition IV dataset IIa) and compared with several other competing classification methods. Experimental results showed that the proposed CDECL based methods can effectively construct a diversity ensemble classifier and exhibits superior classification performance in comparison with several competing methods.Significance. The proposed method is promising for improving the performance of MI-based BCIs.


Assuntos
Interfaces Cérebro-Computador , Algoritmos , Eletroencefalografia/métodos , Imagens, Psicoterapia , Imaginação , Aprendizado de Máquina
14.
Sci Total Environ ; 720: 137711, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32325605

RESUMO

The phosphorus (P) supply is mismatched with rice demand in the early and late stages of rice growth, which primarily results in low P use efficiency and high environmental risk. In recent years, the use of the natural periphyton in nutrient regulation in paddy fields has attracted much research interest. However, a mechanistic understanding of the action of periphyton on P biogeochemical cycling during the pivotal stages of rice growth has received little attention. In this study, the influence of periphyton proliferation on the soil surface and its consequential decomposition on P migration and bioavailability were investigated in two paddy soils using two microcosm experiments. The results showed that periphyton rapidly accumulated fertilizer P when it proliferated on the soil surface under favorable light condition, which led to more fertilizer P being stored on the soil surface and less P being fixed by soil particles or transported via runoff into the water bodies. The decomposition of periphyton under unfavorable light condition not only increased soil soluble reactive P, but also increased the amount of easily available P species, such as labile P, AlP, FeP, and mobilized OP. Thus, periphyton colonizing the soil surface in the early stage of rice growth could act as a P sink and decrease the P environmental risk, and its decomposition in the late stage of rice growth could act as a P source and activator. Phosphorus bioavailability regulated by periphyton could be synchronous with rice needs. Thus, periphyton has the potential to increase P use efficiency in paddy fields.


Assuntos
Oryza , Fertilizantes , Perifíton , Fósforo , Solo
15.
Int J Biol Sci ; 16(10): 1753-1766, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226295

RESUMO

The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , Animais , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Antivirais/uso terapêutico , COVID-19 , Quirópteros/virologia , Citocinas/imunologia , Surtos de Doenças , Humanos , Imunização Passiva , Período de Incubação de Doenças Infecciosas , Medicina Tradicional Chinesa , Saúde Mental , Pandemias , Prognóstico , Fatores de Risco , SARS-CoV-2 , Viagem , Vacinação , Soroterapia para COVID-19
16.
Colloids Surf B Biointerfaces ; 181: 215-225, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31146245

RESUMO

The current knowledge of bacterial migration is mainly derived from work using bare or Fe-coated quartz sands as porous media. However, mineral coatings on quartz by phyllosilicates and Al-oxides prevail in natural soils, and their effect on bacterial transport remains unknown. Herein, we systematically explored the transport of two bacterial pathogens (Escherichia coli and Staphylococcus aureus) through saturated bare quartz and those coated by kaolinite (KaoQuartz), montmorillonite (MontQuartz) or Al-oxides (AlQuartz) under various solution ionic strength (IS) and pH levels. Elevating IS or decreasing pH discouraged bacterial mobility in all cases, with one exception for the migration of S. aureus through AlQuartz at various IS levels. E. coli showed a higher mobility than S. aureus in all cases. All the three coatings, especially the Al-oxides inhibited bacterial transport through quartz. Overall, the two phyllosilicates-coated sands showed transport behaviors (mobility trends with IS, pH, and cell type) similar to those for the bare quartz which could be explained by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Nevertheless, for transport within AlQuartz, there were deviations between the observations and the DLVO predictions, probably because of the existence of non-DLVO forces such as hydrophobic and chemical interactions. More importantly, the bacterial retention was found to correlate well with the adhesion regardless of the solution condition and the bacteria and media type, thereby revealing a central role of adhesion in mediating migration through mineral-coated sands. These findings highlight the significance of mineral coating and adhesion in pathogen dissemination in natural soils.


Assuntos
Óxido de Alumínio/química , Bentonita/química , Escherichia coli/metabolismo , Caulim/química , Staphylococcus aureus/metabolismo , Aderência Bacteriana , Transporte Biológico , Tamanho da Partícula , Porosidade , Areia/química , Propriedades de Superfície
17.
J Dig Dis ; 20(1): 11-17, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30444028

RESUMO

The current review aimed to elucidate the role of diet in every stage of inflammatory bowel diseases, from aspects of prevention, treatment and rehabilitation. Western diet, characterized by overconsumption of refined sugar and saturated fat and low consumption of dietary fiber, may partly be blamed for its pathogenesis. Some immune-modulated nutrients (fibers, monounsaturated fatty acids, n-3 polyunsaturated fatty acids and vitamin D) exert their potential beneficial effects on gut microbiota and immune function, resulting in clinical remission and/or preventing relapse. However, data is limited to conclude optimal micronutrient levels and therapeutic implications. Further, diet itself is complex; therefore, it is reasonable to evaluate diet as a whole rather than a single type of food. Some specific dietary patterns are generated for the management of inflammatory bowel diseases with controversial results. Only exclusive enteral nutrition has been widely recommended for pediatric patients with non-stricturing active Crohn's disease. Self-monitoring, avoidance of certain types of foods, limited intake of alcohol and smoking, supplementation of minerals and vitamins if deficiency is confirmed, and adherence to the diet enriched in vegetables and fruits and low in animal food and un-digested fiber during flares are the most common dietary recommendation. Further clinical trials with a high evidence rank are warranted.


Assuntos
Dieta/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Doenças Inflamatórias Intestinais/dietoterapia , Doenças Inflamatórias Intestinais/etiologia , Animais , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/fisiopatologia
18.
Ecotoxicol Environ Saf ; 165: 11-18, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30173021

RESUMO

Soil arsenic (As) contamination is a serious concern because of its mark negative impacts on plant growth and physiological processes. In plant-soil system, As competes against phosphorus (P) which depends on charge component of different soil types. The main objective of this study was to investigate the influence of ((NH4)3PO4 (PO43-) and Ca5(PO4)3(OH) (phosphorite)) in ameliorating As stress on plant physiological process against As toxicity and their role in As accumulation. We performed eighteen treatments with different levels of As (0, 35, and 70 mg/kg) and P (0, 100, and 200 mg/kg) against two P sources of PO43- and phosphorite. Overall, more improvement in plant growth was observed by addition of PO43- than phosphorite. Significant increases in plant height (51%), dry biomass (root (49%) and shoot (40%)), chlorophyll contents (88%), total soluble sugars (58%) and plant functional leaves (51%) were observed by PO43- application as compared to their corresponding un-fertilized treatment under As stress conditions. However, proline and MDA contents were decreased by 49% and 71% with PO43- applied, respectively, under As stress. The As and P uptake by soybean were remarkably enhanced by the application of PO43- than phosphorite. Therefore, highly soluble P supplementation has great potential to minimize As-induced damage to plant growth in acidic soils and improve As uptake by plants. The findings obtained in present study will be used as an important tool for amelioration of As polluted acidic soils.


Assuntos
Arsênio/toxicidade , Glycine max/efeitos dos fármacos , Fósforo/metabolismo , Poluentes do Solo/toxicidade , Arsênio/metabolismo , Transporte Biológico , Biomassa , Clorofila/análise , Peroxidação de Lipídeos , Minerais/análise , Minerais/metabolismo , Fosfatos/análise , Fosfatos/metabolismo , Fósforo/análise , Prolina/análise , Poluentes do Solo/metabolismo , Glycine max/química , Glycine max/crescimento & desenvolvimento , Glycine max/metabolismo , Estresse Fisiológico , Açúcares/metabolismo
19.
Iran J Basic Med Sci ; 21(4): 422-426, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29796228

RESUMO

OBJECTIVES: In this study, we aimed to evaluate the effect of salidroside on the activities of the different drug-metabolizing enzymes CYP1A2, CYP2B6, CYP2C9, CYP2D6 and CYP3A4 in rats, in which a specific probe drug was used for each enzyme. MATERIALS AND METHODS: After pretreatment with salidroside, five probe drugs were simultaneously administered to rats by gavage. The given dose was 2.0 mg/kg for phenacetin (CYP1A2 activity), 4.0 mg/kg for bupropion (CYP2B6 activity), 2.0 mg/kg for losartan (CYP2C9 activity), 8.0 mg/kg for metoprolol (CYP2D6 activity) and 1.0 mg/kg for midazolam (CYP3A4 activity). Then, an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the concentrations of rats' blood, which were collected at different corresponding times. RESULTS: Our data showed that salidroside exhibited an inductive effect on CYP1A2, CYP2B6, CYP2C9 and CYP3A4 activities by changing the main pharmacokinetic parameters (t1/2, CL/F, Cmax and AUC(0-∞)) of the four probe drugs in rats. However, no significant changes in CYP2D6 activity were observed. CONCLUSION: In a word, the results displayed that salidroside could induce the activities of CYP1A2, CYP2B6, CYP2C9 and CYP3A4, which may influence the disposition of the drugs that are mainly metabolized by these pathways. Our research can provide the basis for the study of related herb-drug interactions in clinic.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA