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1.
BJU Int ; 134(1): 72-80, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38459675

RESUMO

OBJECTIVES: To investigate the ability of propolis-coated ureteric stents to solve complications, especially urinary tract infections (UTIs) and crusting, in patients with long-term indwelling ureteric stents through antimicrobial and anti-calculus activities. MATERIALS AND METHODS: Polyurethane (PU) ureteric stents were immersed in the ethanol extract of propolis (EEP), a well-known antimicrobial honeybee product, and subjected to chemical, hydrophilic, and seismic tests. The antimicrobial activity of the EEP coating was then examined by in vitro investigation. Proteus mirabilis infection was induced in rats within uncoated and EEP-coated groups, and the infection, stone formation, and inflammation were monitored at various time points. RESULTS: The characterisation results showed that the hydrophilicity and stability of the EEP surface improved. In vitro tests revealed that the EEP coating was biocompatible, could eliminate >90% of bacteria biofilms attached to the stent and could maintain bacteriostatic properties for up to 3 months. The in vivo experiment revealed that the EEP-coating significantly reduced the amount of bacteria, stones, and salt deposits on the surface of the ureteric stents and decreased inflammation in the host tissue. CONCLUSIONS: Compared with clinically used PU stents, EEP-coated ureteric stents could better mitigate infections and prevent encrustation. Thus, this study demonstrated that propolis is a promising natural dressing material for ureteric stents.


Assuntos
Antibacterianos , Materiais Revestidos Biocompatíveis , Própole , Stents , Ureter , Animais , Ratos , Própole/farmacologia , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Proteus mirabilis/efeitos dos fármacos , Masculino , Infecções Urinárias/prevenção & controle , Ratos Sprague-Dawley , Biofilmes/efeitos dos fármacos , Infecções por Proteus/prevenção & controle , Poliuretanos
2.
PLoS Comput Biol ; 19(9): e1011444, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37695793

RESUMO

Different genes form complex networks within cells to carry out critical cellular functions, while network alterations in this process can potentially introduce downstream transcriptome perturbations and phenotypic variations. Therefore, developing efficient and interpretable methods to quantify network changes and pinpoint driver genes across conditions is crucial. We propose a hierarchical graph representation learning method, called iHerd. Given a set of networks, iHerd first hierarchically generates a series of coarsened sub-graphs in a data-driven manner, representing network modules at different resolutions (e.g., the level of signaling pathways). Then, it sequentially learns low-dimensional node representations at all hierarchical levels via efficient graph embedding. Lastly, iHerd projects separate gene embeddings onto the same latent space in its graph alignment module to calculate a rewiring index for driver gene prioritization. To demonstrate its effectiveness, we applied iHerd on a tumor-to-normal GRN rewiring analysis and cell-type-specific GCN analysis using single-cell multiome data of the brain. We showed that iHerd can effectively pinpoint novel and well-known risk genes in different diseases. Distinct from existing models, iHerd's graph coarsening for hierarchical learning allows us to successfully classify network driver genes into early and late divergent genes (EDGs and LDGs), emphasizing genes with extensive network changes across and within signaling pathway levels. This unique approach for driver gene classification can provide us with deeper molecular insights. The code is freely available at https://github.com/aicb-ZhangLabs/iHerd. All other relevant data are within the manuscript and supporting information files.


Assuntos
Aprendizado Profundo , Encéfalo , Aprendizagem , Registros
3.
Eur Radiol ; 34(8): 4883-4896, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38189980

RESUMO

OBJECTIVES: The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). METHODS: Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. RESULTS: A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). CONCLUSIONS: In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. CLINICAL RELEVANCE STATEMENT: The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. KEY POINTS: • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.


Assuntos
Displasia Arritmogênica Ventricular Direita , Ventrículos do Coração , Humanos , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Estudos Prospectivos , Fractais , Adulto , Imageamento por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodos , Morte Súbita Cardíaca
4.
Cell Biol Int ; 48(3): 290-299, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38100125

RESUMO

Oxidized low-density lipoprotein (ox-LDL) causes dysfunction of endothelial progenitor cells (EPCs), and we recently reported that 14-3-3-η can attenuate the damage triggered by ox-LDL in EPCs. However, the molecular mechanisms by which 14-3-3-η protects EPCs from the damage caused by ox-LDL are not fully understood. In this study, we observed that the expression of 14-3-3-η and BCL-2 were downregulated in ox-LDL-treated EPCs. Overexpression of 14-3-3-η in ox-LDL-treated EPC significantly increased BCL-2 level, while knockdown of BCL-2 reduced 14-3-3-η expression and mitigated the protective effect of 14-3-3-η on EPCs. In addition, we discovered that 14-3-3-η colocalizes and interacts with BCL-2 in EPCs. Taken together, these data suggest that 14-3-3-η protects EPCs from ox-LDL-induced damage by its interaction with BCL-2.


Assuntos
Células Progenitoras Endoteliais , Humanos , Apoptose , Células Cultivadas , Células Progenitoras Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipoproteínas LDL/farmacologia , Lipoproteínas LDL/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
5.
Environ Sci Technol ; 58(5): 2393-2403, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38268063

RESUMO

Bulk carbon-based materials can enhance anaerobic biodenitrification when they are present in extracellular matrices. However, little information is available on the effect of nitrogen and iron co-doped carbon dots (N, Fe-CDs) with sizes below 10 nm on this process. This work demonstrated that Fe-NX formed in N, Fe-CDs and their low surface potentials facilitated electron transfer. N, Fe-CDs exhibited good biocompatibility and were effectively absorbed by Pseudomonas stutzeri ATCC 17588. Intracellular N, Fe-CDs played a dominant role in enhancing anaerobic denitrification. During this process, the nitrate removal rate was significantly increased by 40.60% at 11 h with little nitrite and N2O accumulation, which was attributed to the enhanced activities of the electron transport system and various denitrifying reductases. Based on proteomics and metabolomic analysis, N, Fe-CDs effectively regulated carbon/nitrogen/sulfur metabolism to induce more electron generation, less nitrite/N2O accumulation, and higher levels of nitrogen removal. This work reveals the mechanism by which N, Fe-CDs enhance anaerobic denitrification and broaden their potential application in nitrogen removal.


Assuntos
Desnitrificação , Nitritos , Nitritos/metabolismo , Nitritos/farmacologia , Carbono , Anaerobiose , Proteômica , Nitrogênio/metabolismo , Nitrogênio/farmacologia
6.
Arch Gynecol Obstet ; 310(1): 55-67, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38836931

RESUMO

PURPOSE: To summarize evidence on levonorgestrel releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM) and to identify potential research gaps. METHODS: Search was conducted in MEDLINE, The Cochrane Library, EMBASE, CBM, CNKI, and Wanfang. We included studies investigating patients with AM treated with LNG-IUS combined with conservative therapy. RESULTS: Thirty-nine studies compared LNG-IUS with other conservative therapeutic drugs. The most common comparison was GnRH-a + LNG-IUS vs. LNG-IUS alone, followed by LNG-IUS vs. mifepristone, expected treatment, and GnRH-a. GnRH-a + LNG-IUS was more beneficial in reducing the intensity of dysmenorrhea than LNG-IUS alone at the 6-month follow-up in patients with an enlarged uterus and moderate to severe dysmenorrhea. Large and well-designed studies are needed to confirm the efficacy of LNG-IUS and GnRH-a on reducing uterine volume at 6-month follow-up. Thirty-two studies investigated LNG-IUS as the postoperative management. The most common comparison was surgical excision + LNG-IUS vs. surgical excision. Results showed VAS scores were lower in the surgical excision + LNG-IUS group than in the surgical excision group at the 1-year follow-up. Evidence on endometrial thickness, quality of life, adverse events and beneficial effect at 3 and 5 years are needed. CONCLUSIONS: Combined GnRH-a and LNG-IUS treatment was more efficacious than LNG-IUS alone for patients with an enlarged uterus and moderate to severe dysmenorrhea. Moreover, LNG-IUS seemed to show potential long-term benefits in postoperative therapy, warranting further meta-analysis for confirmation.


Assuntos
Adenomiose , Dismenorreia , Dispositivos Intrauterinos Medicados , Levanogestrel , Humanos , Feminino , Levanogestrel/administração & dosagem , Adenomiose/tratamento farmacológico , Dismenorreia/tratamento farmacológico , Resultado do Tratamento , Hormônio Liberador de Gonadotropina/agonistas , Contraceptivos Hormonais/administração & dosagem , Mifepristona/administração & dosagem , Mifepristona/uso terapêutico
7.
Angew Chem Int Ed Engl ; 63(16): e202319982, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38361437

RESUMO

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine and nanotechnology, artificial nanozymes offer advanced controllability and functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity and biosafety, still exist between nanozymes and their native counterparts. Here we report a non-metal single-selenium (Se)-atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mimetic activity. This novel single atom nanozyme provides a safe alternative to conventional metal-based catalysts and effectively cuts off the cellular energy and reduction equivalents through its distinctive catalytic function in tumors. In this study, we have demonstrated the substantial efficacy of SeSAE as an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism of the NADPH oxidase-like activity of the non-metal SeSAE was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation of the biological functions, cell death pathways, and metabolic remodeling effects of the nanozyme was conducted, aiming to provide valuable insights into the development of single atom nanozymes with clinical translation potential.


Assuntos
Nanotecnologia , Neoplasias , Animais , Camundongos , Metais , Catálise , Neoplasias/tratamento farmacológico , Nanomedicina
8.
Br J Cancer ; 128(5): 793-804, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36522478

RESUMO

BACKGROUND: This study aims to develop an attention-based deep learning model for distinguishing benign from malignant breast lesions on CESM. METHODS: Preoperative CESM images of 1239 patients, which were definitely diagnosed on pathology in a multicentre cohort, were divided into training and validation sets, internal and external test sets. The regions of interest of the breast lesions were outlined manually by a senior radiologist. We adopted three conventional convolutional neural networks (CNNs), namely, DenseNet 121, Xception, and ResNet 50, as the backbone architectures and incorporated the convolutional block attention module (CBAM) into them for classification. The performance of the models was analysed in terms of the receiver operating characteristic (ROC) curve, accuracy, the positive predictive value (PPV), the negative predictive value (NPV), the F1 score, the precision recall curve (PRC), and heat maps. The final models were compared with the diagnostic performance of conventional CNNs, radiomics models, and two radiologists with specialised breast imaging experience. RESULTS: The best-performing deep learning model, that is, the CBAM-based Xception, achieved an area under the ROC curve (AUC) of 0.970, a sensitivity of 0.848, a specificity of 1.000, and an accuracy of 0.891 on the external test set, which was higher than those of other CNNs, radiomics models, and radiologists. The PRC and the heat maps also indicated the favourable predictive performance of the attention-based CNN model. The diagnostic performance of two radiologists improved with deep learning assistance. CONCLUSIONS: Using an attention-based deep learning model based on CESM images can help to distinguishing benign from malignant breast lesions, and the diagnostic performance of radiologists improved with deep learning assistance.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Humanos , Feminino , Sensibilidade e Especificidade , Mama/diagnóstico por imagem , Mamografia/métodos , Redes Neurais de Computação , Neoplasias da Mama/patologia
9.
Antimicrob Agents Chemother ; 67(6): e0009823, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37140388

RESUMO

Spinal cystic echinococcosis, a severely neglected, rare disease, is characterized by high morbidity, disability, and mortality in prevalent regions. Due to the high-risk nature of surgical treatment and the ineffectiveness of conventional drugs, there is an unmet need for novel safe and effective drugs for the treatment of this disease. In this study, we examined the therapeutic effects of α-mangostin for spinal cystic echinococcosis, and explored its potential pharmacological mechanism. The repurposed drug exhibited a potent in vitro protoscolicidal effect and significantly inhibited the evolution of larval encystation. Moreover, it demonstrated a remarkable anti-spinal cystic echinococcosis effect in gerbil models. Mechanistically, we found that α-mangostin intervention led to intracellular depolarization of mitochondrial membrane potential and reactive oxygen species generation. In addition, we observed elevated expression of autophagic proteins, aggregation of autophagic lysosomes, activated autophagic flux, and disrupted larval microstructure in protoscoleces. Further metabolite profiling showed that glutamine was imperative for autophagic activation and anti-echinococcal effects mediated by α-mangostin. These results suggest that α-mangostin is a potentially valuable therapeutic option against spinal cystic echinococcosis through its effect on glutamine metabolism.


Assuntos
Equinococose , Xantonas , Humanos , Glutamina/uso terapêutico , Equinococose/tratamento farmacológico , Xantonas/farmacologia , Proteínas
10.
J Magn Reson Imaging ; 57(6): 1842-1853, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36219519

RESUMO

BACKGROUND: Previous studies have explored the potential on radiomics features of primary breast cancer tumor to identify axillary lymph node (ALN) metastasis. However, the value of deep learning (DL) to identify ALN metastasis remains unclear. PURPOSE: To investigate the potential of the proposed attention-based DL model for the preoperative differentiation of ALN metastasis in breast cancer on dynamic contrast-enhanced MRI (DCE-MRI). STUDY TYPE: Retrospective. POPULATION: A total of 941 breast cancer patients who underwent DCE-MRI before surgery were included in the training (742 patients), internal test (83 patients), and external test (116 patients) cohorts. FIELD STRENGTH/SEQUENCE: A 3.0 T MR scanner, DCE-MRI sequence. ASSESSMENT: A DL model containing a 3D deep residual network (ResNet) architecture and a convolutional block attention module, named RCNet, was proposed for ALN metastasis identification. Three RCNet models were established based on the tumor, ALN, and combined tumor-ALN regions on the images. The performance of these models was compared with ResNet models, radiomics models, the Memorial Sloan-Kettering Cancer Center (MSKCC) model, and three radiologists (W.L., H.S., and F. L.). STATISTICAL TESTS: Dice similarity coefficient for breast tumor and ALN segmentation. Accuracy, sensitivity, specificity, intercorrelation and intracorrelation coefficients, area under the curve (AUC), and Delong test for ALN classification. RESULTS: The optimal RCNet model, that is, RCNet-tumor+ALN , achieved an AUC of 0.907, an accuracy of 0.831, a sensitivity of 0.824, and a specificity of 0.837 in the internal test cohort, as well as an AUC of 0.852, an accuracy of 0.828, a sensitivity of 0.792, and a specificity of 0.853 in the external test cohort. Additionally, with the assistance of RCNet-tumor+ALN , the radiologists' performance was improved (external test cohort, P < 0.05). DATA CONCLUSION: DCE-MRI-based RCNet model could provide a noninvasive auxiliary tool to identify ALN metastasis preoperatively in breast cancer, which may assist radiologists in conducting more accurate evaluation of ALN status. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Metástase Linfática , Feminino , Humanos , Neoplasias da Mama/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
11.
BMC Neurol ; 23(1): 32, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36670390

RESUMO

BACKGROUND: The carriers of damaging heterozygous variants in interferon regulatory factor 2 binding protein-like (IRF2BPL), encoding a member of the IRF2BP family of transcriptional regulators, may be affected by a variety of neurological symptoms, such as neurodevelopmental regression, language and motor developmental delay, seizures, progressive ataxia and a lack of coordination, and even dystonia. CASE PRESENTATION: We report a Chinese boy who presented with dystonia, dysarthria, and normal development due to nonsense IRF2BPL mutation, with intact imaging and EEG findings but without developmental delays or seizures. Whole-exome sequencing revealed a novel nonsense variant IRF2BPL (NM_024496) Exon C.562C > T (p.Arg188*). CONCLUSION: This case report presents a Chinese boy with a novel nonsense variant in IRF2BPL, displaying rapid progressive dystonia and dysarthria, without early developmental delay or epilepsy; expands the IRF2BPL phenotypes in the Chinese population; and raises awareness of patients with IRF2BPL.


Assuntos
Distonia , Distúrbios Distônicos , Humanos , Proteínas de Transporte/genética , Disartria , Distonia/genética , População do Leste Asiático , Idioma , Mutação , Proteínas Nucleares/genética , Convulsões/genética
12.
BMC Infect Dis ; 23(1): 637, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37770837

RESUMO

BACKGROUND: Concurrent non-alcoholic fatty liver disease (NAFLD) is common in patients with chronic HBV infection. But the impact of fatty liver on the histologic progression of HBV infection remains controversial. METHODS: Consecutive HBV-infected patients who underwent liver biopsy between 2016 and 2021 were included. Alcohol consumption and other types of viral hepatitis were excluded. All biopsies were scored for grading and staging by Scheuer's score, and the steatosis was scored as an estimate of the percentage of liver parenchyma replaced by fat. Logistic regression analyses were applied to assess the associated factors for significant liver inflammation (G ≥ 2), significant fibrosis (S ≥ 2) and advanced fibrosis (S ≥ 3). RESULTS: Among the 871 HBV-infected patients, hepatic steatosis was prevalent in 255 patients (29.28%). Significant liver inflammation was present in 461 patients (52.93%). Significant fibrosis was observed in 527 patients (60.51%), while advanced liver fibrosis was observed in 171 patients (19.63%). Patients with concomitant NAFLD were more likely to have significant liver inflammation and advanced fibrosis. Fatty liver was an independent risk factor for significant liver inflammation (OR: 2.117, 95% CI: 1.500-2.988), but it could not predict the development of fibrosis. Especially, in HBV-infected patients with persistent normal ALT (immune tolerant and inactive carrier phase), the presence of significant liver inflammation was higher in NAFLD than those without NAFLD. The prevalence of advanced liver fibrosis was higher in NAFLD than non-NAFLD only in the immune tolerant phase, while NAFLD did not increase fibrosis burden in other stages of HBV infection. We developed a predictive model for significant liver inflammation with the area under receiver operating characteristic curve (AUROC) of 0.825, and a model for significant fibrosis with the AUROC of 0.760. CONCLUSIONS: NAFLD is independently associated with significant liver inflammation, and increases the burden of advanced liver fibrosis in HBV-infected patients. The influence of NAFLD on the degree of liver inflammation and fibrosis is different in distinct clinical phases of chronic HBV infection.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Vírus da Hepatite B , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Fibrose , Biópsia , Inflamação/complicações
13.
J Sep Sci ; 46(1): e2200656, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36285382

RESUMO

This paper reports a method for determining the carbonate content in barite ore using headspace gas chromatography. Based on the acidification reaction, the carbonate in the barite ore was converted to CO2 in a closed headspace vial. When the carbonate content was significant, the pressure caused changes in the CO2 and O2 signals and affected the measurement accuracy. It was found that carbonate content is proportional to the intensity ratio of the CO2 to O2 signals. Thus, the carbonate content in barite ore can be measured indirectly using a theoretical model. The results showed that the carbonate in 3 g of barite ore sample with a particle size of 74 µm could react completely with a hydrochloric acid solution (2 mol/L) at 65°C for 5 min. The method described herein had good precision (relative standard deviation < 4.14%) and accuracy (relative differences < 6.12%). Further, the limit of quantification was 0.07 mol/L. Owing to its simplicity and speed, this method can be used for the batch determination of carbonate content in barite ore.


Assuntos
Sulfato de Bário , Dióxido de Carbono , Carbonatos , Ácidos , Cromatografia Gasosa/métodos
14.
J Sep Sci ; 46(17): e2300331, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37438987

RESUMO

An efficient strategy for the identification of potential nephroprotective substances in Zhu-Ling decoction has been established with the integration of absorbed components characterization, pharmacokinetics, and activity evaluation. A qualitative method was developed to characterize the chemical constituents absorbed components in vivo of Zhu-Ling decoction by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. A quantitative method was established and validated for the simultaneous determination of eight compounds in rat plasma by using ultra-performance liquid chromatography-triple quadruple tandem mass spectrometry. Finally, the nephroprotective activities of absorbed components with high exposure were assessed by cell survival rate, superoxide dismutase, and malondialdehyde activities in hydrogen peroxide-induced Vero cells. As a result, 111 compounds in Zhu-Ling decoction and 36 absorbed components were identified in rat plasma and urine, and poricoic acid A, poricoic acid B, alisol A, 16-oxo-alisol A, and dehydro-tumulosic acid had high exposure levels in rat plasma. Finally, poricoic acid B, poricoic acid A, 16-oxo-alisol A, and dehydro-tumulosic acid showed remarkable nephroprotective activity against Vero cells damage induced by hydrogen peroxide. Besides, superoxide dismutase and malondialdehyde activities were obviously regulated in hydrogen peroxide-induced Vero cells by treatment with the four compounds mentioned above. Therefore, these four compounds were considered to be effective substances of Zhu-Ling decoction due to their relatively high exposure in vivo and biological activity. This study provided a chemical basis for the action mechanism of Zhu-Ling decoction in the treatment of chronic kidney diseases.


Assuntos
Medicamentos de Ervas Chinesas , Triterpenos , Chlorocebus aethiops , Ratos , Animais , Peróxido de Hidrogênio , Células Vero , Espectrometria de Massas/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão/métodos
15.
J Sep Sci ; 46(2): e2200723, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36401831

RESUMO

Codonopsis radix was commonly used as food materials or herbal medicines in many countries. However, the comprehensive analysis of chemical constituents, and in vivo xenobiotics of Codonopsis radix remain unclear. In the present study, an integrated strategy with feature-based molecular networking using ultra-high-performance liquid chromatography coupled with mass spectrometry was established to systematically screen the chemical constituents and the in vivo xenobiotics of Codonopsis radix. A step-by-step manner based on a composition database, visual structure classification, discriminant ions, and metabolite software prediction was proposed to overcome the complexities due to the similar structure of chemical constituents and metabolites of Codonopsis radix. As a result, 103 compounds were tentatively characterized, 20 of which were identified by reference standards. Besides, a total of 50 xenobiotics were detected in vivo, including 26 prototypes and 24 metabolites, while the metabolic features of the pyrrolidine alkaloids were elucidated for the first time. The metabolism reactions of pyrrolidine alkaloids and sesquiterpene lactones included oxidation, methylation, hydration, hydrogenation, demethylation, glucuronidation, and sulfation. This study provided a generally applicable approach to the comprehensive investigation of the chemical and metabolic profile of traditional Chinese medicine and offered reasonable guidelines for further screening of quality control indicators and pharmacodynamics mechanism of Codonopsis radix.


Assuntos
Alcaloides , Codonopsis , Medicamentos de Ervas Chinesas , Ratos , Animais , Medicamentos de Ervas Chinesas/análise , Codonopsis/química , Codonopsis/metabolismo , Ratos Sprague-Dawley , Cromatografia Líquida de Alta Pressão/métodos , Xenobióticos/metabolismo , Espectrometria de Massas/métodos , Alcaloides/química , Pirrolidinas
16.
J Enzyme Inhib Med Chem ; 38(1): 2244694, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37558230

RESUMO

In this study, 21 new honokiol derivatives were synthesised, and their anti-cancer properties were investigated. Among these, compound 1g exhibited the most potent cytotoxic activity against human nasopharyngeal carcinoma CNE-2Z cells, human gastric cancer SGC7901 cells, human breast cancer MCF-7 cells, and mouse leydig testicular cancer I-10 lines with IC50 values of 6.04, 7.17, 6.83, and 5.30 µM, respectively. Compared to the parental compound, 1g displayed up to 5.18-fold enhancement of the cytotoxic effect on CNE-2Z cells. We further demonstrated that 1g inhibited cell growth, suppressed migration and invasion, and induced apoptosis of CNE-2Z cells by down-regulating HIF-1α, MMP-2, MMP-9, Bcl-2, Akt and up-regulating Bax protein levels. Transfection of CNE-2Z cells with HIF-1α siRNA reduced cell migration and invasion. In addition, in vivo experiments confirmed that 1g inhibited tumour growth in CNE-2Z cell-xenografted nude mice with low toxicity. Thus, our data suggested that 1g was a potent and safe lead compound for nasopharyngeal carcinoma therapy.


Assuntos
Antineoplásicos , Carcinoma , Neoplasias Nasofaríngeas , Neoplasias Testiculares , Masculino , Humanos , Animais , Camundongos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Camundongos Nus , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
17.
Biodegradation ; 34(4): 341-355, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36808271

RESUMO

Sulfoxaflor (SUL, [N-[methyloxido[1-[6-(trifluoromethyl)-3-pyridinyl] ethyl]-λ4-sulfanylidene] cyanamide]) is a widely used systemic insecticide, and its residue has frequently been detected in the environment, posing a potential threat to the environment. In this study, Pseudaminobacter salicylatoxidans CGMCC 1.17248 rapidly converted SUL into X11719474 via a hydration pathway mediated by two nitrile hydratases (AnhA and AnhB). Extensive (96.4%) degradation of 0.83 mmol/L SUL was achieved by P. salicylatoxidans CGMCC 1.17248 resting cells within 30 min (half-life of SUL 6.4 min). Cell immobilization by entrapment into calcium alginate remediated 82.8% of the SUL in 90 min, and almost no SUL was observed in surface water after incubation for 3 h. P. salicylatoxidans NHases AnhA and AnhB both hydrolyzed SUL to X11719474, although AnhA exhibited much better catalytic performance. The genome sequence of P. salicylatoxidans CGMCC 1.17248 revealed that this strain could efficiently eliminate nitrile-containing insecticides and adapt to harsh environments. We firstly found that UV irradiation transforms SUL to the derivatives X11719474 and X11721061, and the potential reaction pathways were proposed. These results further deepen our understanding of the mechanisms of SUL degradation as well as the environmental fate of SUL.


Assuntos
Inseticidas , Raios Ultravioleta , Fotólise , Inseticidas/química , Inseticidas/metabolismo , Biodegradação Ambiental
18.
Reprod Health ; 20(1): 156, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37865796

RESUMO

BACKGROUND: The aim of the study is to investigate the proportion and clinical features of previous spontaneously ruptured ovarian endometrioma among women who underwent elective surgery for endometrioma. METHODS: This retrospective study was based on a cohort of elective surgeries for endometrioma performed by the same gynecologic team at Peking Union Medical College Hospital from January 2017 to October 2022. Patients diagnosed with previous spontaneously ruptured endometrioma during elective surgery were enrolled in the ruptured group. In the same cohort, patients with unruptured endometrioma treated during the same period were selected as the unruptured group by 1:2 matching according to age. Demographic and clinical information were collected and compared between two groups. RESULTS: A total of 422 patients in the cohort were diagnosed with endometrioma. There were 38 patients (9.0%) in ruptured group and 76 patients in unruptured group. All enrolled participants were treated by laparoscopic surgery. In ruptured group, 86.8% patients had a history of acute abdominal pain, which was only 13.2% in unruptured group (P < 0.001). Compared to unruptured group, patients diagnosed with ruptured endometrioma had a lower BMI (P = 0.021), larger maximum diameter of endometrioma (P = 0.040), higher proportion of cul-de-sac partial obliteration rather than complete obliteration (P = 0.003). CONCLUSIONS: Spontaneous rupture of endometrioma is not rare. The proportion of spontaneous rupture of endometrioma in our study was higher than that reported in the literatures. In women with endometrioma, the onset of acute abdominal pain should be considered a rupture of cyst, especially in patients with big cysts.


Assuntos
Endometriose , Humanos , Feminino , Estudos de Casos e Controles , Endometriose/complicações , Endometriose/cirurgia , Estudos Retrospectivos , Ruptura Espontânea/cirurgia , Dor Abdominal
19.
Arch Gynecol Obstet ; 307(1): 163-168, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35482067

RESUMO

PURPOSE: To classify abdominal wall endometriosis (AWE) according to the invasive levels of tissue mass, and to compare the differences in clinical characteristics between different types of AWE. METHODS: In this study, we retrospectively analyzed the clinical data of 367 patients who had undergone resection of abdominal-wall endometriotic lesions at the Peking Union Medical College Hospital from January 2008 to December 2018, and we divided the patients into three types according to their deepest level of lesion invasion. Type I designated invasion of skin and subcutaneous tissue; type II, of fascia and rectus abdominis; and type III, of peritoneum. We classified, compared, and analyzed the general conditions, clinical manifestations, auxiliary examinations, surgical conditions, postoperative conditions, and recurrence status of patients. RESULTS: Of the 367 patients, type I patients accounted for 13.62%, type II patients for 56.68%, and type III for 29.7%. With respect to group comparisons, we observed that as the location of the mass deepened, the rate of concurrent pelvic endometriosis increased (P = 0.007), recurrent AWE was augmented (P = 0.02), the size of the mass increased (P < 0.001), the rate of multiple lesions became elevated (P < 0.001), the rate of mesh implantation increased (P < 0.001), the length of postoperative hospital stay (P < 0.001) was lengthened, the number of postoperative fever cases (P = 0.006) increased, and the risk of drainage placement (P < 0.001) was enhanced. The 5-year cumulative recurrence rate was 3.3%, and there was no significant difference in the recurrence rate among various types of AWE. CONCLUSION: Type III AWE carries more severe clinical manifestations, larger lesion size, longer operative time, greater intraoperative surgical difficulty, higher necessity of mesh implantation, and longer postoperative recovery process. Complete resection of AWE lesion is the main therapeutically approach and shows relatively low long-term recurrency rate.


Assuntos
Parede Abdominal , Endometriose , Feminino , Humanos , Gravidez , Endometriose/cirurgia , Endometriose/patologia , Parede Abdominal/cirurgia , Parede Abdominal/patologia , Estudos Retrospectivos , Cesárea , Resultado do Tratamento
20.
Ophthalmic Plast Reconstr Surg ; 39(3): e75-e78, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36807287

RESUMO

A 4-year-old boy with a known diagnosis of neurofibromatosis 1 (NF1) and a diffusely infiltrative plexiform neurofibroma (PN) of the left orbit was started on selumetinib treatment for progressively worsening amblyopia. The patient first presented with new-onset left ptosis at 11 months old. He subsequently developed refractory anisometropic amblyopia of the left eye, in addition to clinically significant left proptosis and hypoglobus that interfered with glasses wear for his amblyopia treatment. The plexiform neurofibroma was not amenable to surgical resection and selumetinib treatment was initiated 3 years after the initial diagnosis. The patient showed remarkable clinical and radiographic improvement in tumor burden after treatment. Best corrected visual acuity improved from 20/50 to 20/20- in his amblyopic eye. Relative proptosis of the affected eye also improved from 4mm to 2mm on Hertel measurements, which allowed for consistent glasses wear. Adverse effects from the treatment were limited to an acneiform rash, which resolved following dose reduction according to the FDA dosing guidelines.


Assuntos
Ambliopia , Exoftalmia , Neurofibroma Plexiforme , Neurofibromatose 1 , Masculino , Humanos , Pré-Escolar , Lactente , Neurofibroma Plexiforme/complicações , Neurofibroma Plexiforme/diagnóstico , Neurofibroma Plexiforme/tratamento farmacológico , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/tratamento farmacológico
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