Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 69
Filtrar
1.
J Chromatogr A ; 1636: 461794, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33341433

RESUMO

A rapid, simple, and generic analytical method for the simultaneous determination of 140 undesirable low-weight pesticides and mycotoxins from different chemical classes in black tea was developed. The method involved swelling the sample in ammonium acetate buffer, extraction with acetonitrile-dimethyl sulfoxide, cleanup by dual dispersive solid-phase extraction (D-SPE) with the assistance of low-temperature centrifugation, and analysis by ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry using multiple reaction monitoring mode. The interferences in the extract were eliminated by the combination of dual d-SPE using only C18 sorbent and anhydrous magnesium sulfate, which maintained the chromatographic column under the ideal condition for a long time and enabled satisfactory recoveries of hydrophobic and hydrophilic analytes simultaneously. Matrix-matched calibration curves were obtained for most target compounds with linear regression coefficients above 0.9900. The limits of quantification (LOQs) ranged within 0.5-10.0 µg/kg, which were usually sufficient to verify the compliance of products with legal tolerances. Satisfactory recoveries of 64.5%-138.1% were obtained in black ta samples with the relative standard deviation (RSD) values between 1.8 and 25.9%. The inter-day precision ranged within 2.2%-24.9%. For over 90% of the analytes, the recoveries were between 70% and 120%, with RSD values below 15.0%. The application of this method in routine monitoring programs can drastically reduce effort and time.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Micotoxinas/análise , Praguicidas/análise , Espectrometria de Massas em Tandem/métodos , Chá/química , Acetonitrilos/química , Tampões (Química) , Dimetil Sulfóxido/química , Reprodutibilidade dos Testes , Extração em Fase Sólida , Espectrometria de Massas por Ionização por Electrospray
2.
Ultrasound Med Biol ; 47(2): 288-295, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33234327

RESUMO

The aim of study was to explore the correlation between shear wave elastography (SWE) and grade group (GG) of prostate cancer (PCa). This retrospective study involved prostate-specific antigen elevated patients with elevated prostate-specific antigen levels who underwent SWE before transrectal ultrasound-guided needle biopsy. A total of 49 PCa lesions were reviewed after radical prostatectomy; 3-7 regions of interest were placed within the cancerous area on axial view compared with the tumor foci outlined on the slides by pathologist. The maximum SWE value was measured, quantitative SWE parameters (Emax, Emean, Emin and standard deviation [SD]) were recorded and correlated with GG and then parameters were compared between indolent (≤2) and aggressive (≥3) GGs. The diagnostic value of each parameter was compared with the receiver operating characteristic curve. Forty-nine PCa foci were divided into two groups on the basis of their GGs. All SWE parameters exhibited a significant linear trend with GG. The area under the receiver operating characteristic curve (AUC) was 0.816 for Emax; with a cutoff point of 84 kPa, sensitivity and specificity were 81.3% and 82.4% to differentiate low and high GGs in PCa. The AUC was 0.776 for Emean; with a cutoff point of 71 kPa, sensitivity and specificity were 78.1% and 76.5%. For Emin, the AUC was 0.739; with a cutoff point of 60 kPa, sensitivity and specificity were 68.8% and 70.6%. For SD, the AUC was 0.681; with a cutoff point of 8.3 kPa, sensitivity and specificity were 46.9% and 94.1%. There were no significant differences between the four SWE parameters (p < 0.05 for all). SWE features were correlated with GGs, and this correlation may have excellent diagnostic performance in predicting high GG in PCa.

3.
Bioorg Chem ; : 104518, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33303210

RESUMO

A series of (E)-N-2(5H)-furanonyl sulfonyl hydrazone derivatives have been rationally designed and efficiently synthesized by one-pot reaction with good yields for the first time. This green approach with wide substrate range and good selectivity can be achieved at room temperature in a short time in the presence of metal-free catalyst. The cytotoxic activities against three human cancer cell lines of all newly obtained compounds have been evaluated by MTT assay. Among them, compound 5 k exhibits high cytotoxic activity against MCF-7 human breast cancer cells with an IC50 value of 14.35 µM. The cytotoxic mechanism may involve G2/M phase arrest pathway, which is probably caused by activating DNA damage. Comet test and immunofluorescence results show that compound 5 k can induce DNA damage in time- and dose-dependent manner. Importantly, 5 k also can effectively inhibit the proliferation of MCF-7 cells and angiogenesis in the zebrafish xenograft model. It is potential to further develop N-2(5H)-furanonyl sulfonyl hydrazone derivatives as potent drugs for breast cancer treatment with higher cytotoxic activity by modifying the structure of the compound.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33186278

RESUMO

STUDY DESIGN: An ex vivo study of the rabbit's vertebral endplate. OBJECTIVE: To assess the effect of axial compression and distraction on vascular buds and VEGFA expression of the VEP. SUMMARY OF BACKGROUND DATA: The abnormal load can lead to intervertebral disc degeneration (IDD), while axial distraction can delay this process. The effects of different mechanical loads on the intervertebral disc (IVD) have been hypothesized to be related to changes in the vascular buds of the vertebral endplate (VEP), moreover, the process that might involve the vascular endothelial growth factor (VEGF) within the VEP. METHODS: Rabbit spinal segments (n = 40) were harvested and randomly classified into four groups: Control group, no stress was applied; Group A, a constant compressive load applied; Group B, compression load removed for a fixed time daily on a continuous basis, and substituted with a distraction load for 30 min; and Group C, compression removed for 30 min for a fixed period daily on a continuous basis. Tissue specimens were collected prior to the culture (day 0) and on day 14 post-culture of each group for analysis of IVDs' morphology, and protein and mRNA expression of Aggrecan, COL2al, VEGFA, and VEGFR2 of the VEPs. RESULTS: Application of axial distraction and dynamic load compression significantly delayed time-and constant compression-mediated VEP changes and IDD. Moreover, the degree of degeneration was associated with loss of vascular buds, as well as the downregulation of VEGFA and its receptor. CONCLUSIONS: The regulation of vascular buds and VEGF expression in the VEP represents one of the mechanisms of axial distraction and dynamic loading. LEVEL OF EVIDENCE: N/A.

5.
Cancer Res ; 80(24): 5583-5596, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33093168

RESUMO

T-cell exhaustion was initially identified in chronic infection in mice and was subsequently described in humans with cancer. Although the distinct signature of exhausted T (TEX) cells in cancer has been well investigated, the molecular mechanism of T-cell exhaustion in cancer is not fully understood. Using single-cell RNA sequencing, we report here that TEX cells in esophageal cancer are more heterogeneous than previously clarified. Sprouty RTK signaling antagonist 1 (SPRY1) was notably enriched in two subsets of exhausted CD8+ T cells. When overexpressed, SPRY1 impaired T-cell activation by interacting with CBL, a negative regulator of ZAP-70 tyrosine phosphorylation. Data from the Tumor Immune Estimation Resource revealed a strong correlation between FGF2 and SPRY1 expression in esophageal cancer. High expression of FGF2 was evident in fibroblasts from esophageal cancer tissue and correlated with poor overall survival. In vitro administration of FGF2 significantly upregulated expression of SPRY1 in CD8+ T cells and attenuated T-cell receptor-triggered CD8+ T-cell activation. A mouse tumor model confirmed that overexpression of FGF2 in fibroblasts significantly upregulated SPRY1 expression in TEX cells, impaired T-cell cytotoxic activity, and promoted tumor growth. Thus, these findings identify FGF2 as an important regulator of SPRY1 expression involved in establishing the dysfunctional state of CD8+ T cells in esophageal cancer. SIGNIFICANCE: These findings reveal FGF2 as an important regulator of SPRY1 expression involved in establishing the dysfunctional state of CD8+ T cells and suggest that inhibition of FGF2 has potential clinical value in ESCC. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/24/5583/F1.large.jpg.

6.
Clin Breast Cancer ; 20(6): e786-e793, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32863154

RESUMO

INTRODUCTION: The purpose of this study was to evaluate the diagnostic performance of superb microvascular imaging (SMI) in breast lesions. MATERIALS AND METHODS: Eighty-five solid breast lesions were studied with color Doppler flow imaging (CDFI), power Doppler imaging (PDI), monochromatic SMI (mSMI), and contrast-enhanced ultrasonography (CEUS). The penetrating vessels (PVs) and microvascular morphologic and distribution features of the breast tumors were evaluated for each modality. RESULTS: The diagnostic accuracies of CDFI, PDI, mSMI, and CEUS were calculated and compared. Surgical pathologic analysis showed 47 benign and 38 malignant lesions. Compared with CDFI and PDI, mSMI and CEUS detected more PVs in breast lesions. The microvascular architecture showed significant differences between benign and malignant lesions. Benign lesions mainly displayed avascular, line-like, and branch-like patterns, and malignant lesions tended to display root hair-like and crab claw-like patterns. mSMI and CEUS identified more root hair-like and crab claw-like patterns in malignant lesions than CDFI and PDI. The sensitivity, negative predictive value, and accuracy of mSMI findings in diagnosing malignancy based on PVs and vascular patterns were both higher than those of CDFI and PDI. CONCLUSIONS: mSMI is equal to CEUS and superior to CDFI and PDI in identifying microvascular and discriminating malignant and benign breast masses.

7.
Ther Adv Med Oncol ; 12: 1758835920942367, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32843902

RESUMO

Objective: This study aimed to evaluate the correlation between cervical lymph node metastasis (CLNM) and each of the ultrasound features, immunohistochemical factors, and B-type Raf (BRAFV600E) mutation. Methods: A retrospective analysis was performed on 405 patients with single papillary thyroid carcinoma (PTC) nodules, all of whom underwent preoperative sonographic examinations, including gray-scale ultrasound, color Doppler ultrasound, and contrast-enhanced ultrasound (CEUS). All PTC patients were evaluated using 14 clinical and sonographic features, eight immunohistochemical factors, and BRAFV600E. Multivariate analyses were performed to identify the risk factors for CLNM, and an equation for CLNM was established. The diagnostic value of each modality was compared with a receiver operating characteristic (ROC) curve. Results: Among the 405 PTC nodules removed surgically, CLNM was confirmed in 138 patients, whereas extrathyroidal extension was confirmed in 185 patients. Multivariate analyses indicated significant differences between CLNM and non-CLNM groups in three conventional ultrasound features (p < 0.05), whereas other sonographic features, eight immunohistochemical factors, and BRAFV600E did not indicate significant differences. A ROC curve of 0.757 in the equation exhibited a significant difference compared with the solo factors (p < 0.05 for all). Hyper or isoechoic enhancement at peak time on CEUS was associated with CLNM, whereas the presence of the BRAFV600E mutation was associated with extrathyroidal extensions although BRAF appeared to be uncorrelated with CLNM in the present study. Conclusion: Intensity at peak time, homogeneity, and size are the three most significant features in predicting CLNM in PTC patients, and the presence of the BRAFV600E mutation was associated with extrathyroidal extensions when PTCs showed a hyper or isoechoic enhancement at peak time in CEUS.

8.
PLoS One ; 15(6): e0234747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584845

RESUMO

SUMMARY OF BACKGROUND DATA: The vascular buds in the vertebral endplate (VEP) are the structural foundation of nutrient exchange in the intervertebral disc (IVD). VEGF is closely related to angiogenesis in the endplate and intervertebral disc degeneration (IDD). OBJECTIVE: To investigate the effects of static load on vascular buds and VEGF expression in the VEP and to further clarify the relation between IDD and VEGF. METHODS: IVD motion segments were harvested from rabbit lumbar spines and cultured under no-loading conditions (controls) or in custom-made apparatuses under a constant compressive load (0.5 MPa) for up to 14 days. Tissue integrity and the number of vascular buds were determined, and the concentrations and expression of Aggrecan, COL2a1, and VEGFA in the VEPs were assessed after 3, 7, and 14 days of culturing and then compared with those of fresh tissues. RESULTS: Under the constant compression, the morphological integrity of the VEPs was gradually disrupted, and immunohistochemistry results showed a significant decrease in the levels of Agg and COL2a1. During the static load, the number of vascular buds in the VEPs was gradually reduced from the early stage of culture, and ELISA showed that the constant compressive load caused a significant decrease in the VEGFA and VEGFR2 protein concentrations, which were consistent with the immunohistochemistry results. Western blot and RT-PCR results also showed that the loading state caused a significant decrease in VEGFA expression compared with that of fresh and control samples. CONCLUSIONS: Constant compression caused degeneration of the VEP as well as a decreased number of vascular buds, thereby accelerating disc degeneration. VEGFA is involved in this process. We anticipate that regulating the expression of VEGFA may improve the condition of the lesions to the vascular buds in the endplates, thus enhancing the nutritional supply function in IVD and providing new therapeutic targets and strategies for the effective prevention and treatment of IDD.


Assuntos
Vasos Sanguíneos/fisiologia , Regulação da Expressão Gênica , Disco Intervertebral/irrigação sanguínea , Disco Intervertebral/metabolismo , Estresse Mecânico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Técnicas de Cultura , Masculino , Coelhos
9.
Zhongguo Zhong Yao Za Zhi ; 45(3): 609-616, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237520

RESUMO

The aim of this paper was to investigate the key targets and mechanism of "Epimedii Folium-Paeoniae Radix Alba" in the treatment of lumbar disc herniation by means of network pharmacology. The currently recognized databases and analysis software at home and abroad were used to construct the network from drugs and diseases. The chemical components of Epimedii Folium and Paeo-niae Radix Alba were collected by using databases such as TCMSP, while their active components were determined and the action targets were predicted according to threshold screening and literature reports. The genes for lumbar disc herniation were collected by using GeneCards, OMIM, and DisGeNET databases. The drug targets were mapped to disease targets, and protein interaction network analysis for key targets, GO function enrichment analysis and KEGG signaling pathway enrichment analysis were performed. Finally, 23 active components of Epimedium Folium and 13 active components of Paeoniae Radix Alba were determined, and a total of 624 drug targets were obtained. After standardization, 214 drug targets were obtained. In addition, 306, 2 and 5 related targets of lumbar disc herniation were collected from GeneCards, OMIM, and DisGeNET database, respectively, and a total of 293 disease targets were obtained after deduplication. After the mapping of drug target and disease target, 44 common targets were obtained. PPI protein interaction network analysis showed that IL-6, TNF, AKT1, MAPK1, and VEGFA may be the core targets for the treatment of lumbar disc herniation. GO enrichment analysis identified 56 items(P<0.05), among which biological processes mainly included immune response, apoptosis, etc.; cell components mainly included extracellular space, extracellular region, etc.; molecular functions mainly included cytokine activity, metallopeptidase activity and so on. Through KEGG pathway enrichment analysis, 91 signaling pathways related to inflammation, metabolism, and senescence were identified, mainly including IL-17 signaling pathway and TNF signaling pathway and so on. "Epimedii Folium-Paeoniae Radix Alba" showed the characteristics of multi-channel and multi-target for the treatment of lumbar disc herniation. This study preliminarily explored the key targets for its role and the biological processes and signaling pathways involved. It was found that it may play a therapeutic role by affecting inflammation and immune regulation, which laid the foundation for further experimental verification.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Epimedium/química , Deslocamento do Disco Intervertebral/tratamento farmacológico , Paeonia/química , Humanos , Vértebras Lombares , Medicina Tradicional Chinesa , Folhas de Planta/química , Raízes de Plantas/química , Transdução de Sinais
10.
BMC Med Imaging ; 20(1): 32, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228606

RESUMO

BACKGROUND: The value of contrast-enhanced ultrasound (CEUS) in differentiating between renal cell carcinoma (RCC) and angiomyolipoma (AML) was analyzed. The purpose of this study was to identify the independent indicators of CEUS for predicting RCC. METHODS: A total of 172 renal tumors (150 RCCs, 22 AMLs) in 165 patients underwent conventional ultrasound (CUS) and CEUS examinations before radical or partial nephrectomy, and the features on CUS and CEUS were analyzed. RESULTS: There were significant differences in echogenicity, blood flow signals in color Doppler flow imaging (CDFI), peak intensity, homogeneity of enhancement, wash in, wash out, and perilesional rim-like enhancement between RCC and AML (P < 0.05 for all). Multivariate analysis indicated that perilesional rim-like enhancement (P = 0.035, odds ratio [OR] = 9.907, 95% confidence interval [CI]: 1.169-83.971) and fast wash out (P = 0.001, OR = 9.755, 95%[CI]: 2.497-38.115) were independent indicators for predicting RCC. The area under the receiver operating characteristic (ROC) curve (AUC) for perilesional rim-like enhancement was 0.838 (95% CI: 0.774-0.890) with 76.7% sensitivity and 90.9% specificity, while the AUC of fast wash out was 0.833 (95% CI:0.768-0.885) with 74.7% sensitivity and 81.8% specificity. CONCLUSIONS: This study indicated that CEUS has value in differentiating RCC and AML. Present perilesional rim-like enhancement and fast wash out may be important indicators for predicting RCC.

11.
Acta Pharmacol Sin ; 41(5): 588-598, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31913348

RESUMO

Vascular dementia (VD) is the second most common dementia disease after Alzheimer's diseases (AD) in the world. Donepezil is used to treat mild to moderate AD, and it has been shown to treat cognitive impairment and memory deficits caused by VD. However, the action mechanism of donepezil against VD has not been clarified. In this study, a bilateral common carotid artery occlusion (BCCAO) model was established in rats to simulate the pathology of VD. Two weeks after the surgery, the rats were administered donepezil (10 mg · kg-1 · d-1, ig) for 3 weeks, and then subjected to behavioral tests. We showed that donepezil treatment significantly improved the performance of BCCAO rats in Morris Water Mazes test and Step-down test. Furthermore, we showed that donepezil treatment significantly attenuated neurodegeneration and restored the synapse dendritic spines density in cortex and hippocampus. We revealed that donepezil treatment significantly increased BDNF expression in cortex and hippocampus. Interestingly, donepezil treatment significantly decreased nuclear translocation of HDAC6 and the binding between HDAC6 and BDNF promoter IV in cortex, but not in the hippocampus. The attenuated neurodegeneration by donepezil in cortex and hippocampus might due to the reduced ROS levels and increased phosphorylation of AMPK, whereas increased phosphorylation of AKT was only detected in cortex. In conclusion, our results demonstrate that donepezil attenuates neurodegeneration in cortex and hippocampus via increasing BDNF expression; the regulation of donepezil on HDAC6 occurred in cortex, but not in the hippocampus. This study further clarifies the pharmacological mechanism of donepezil, while also emphasizes the promising epigenetic regulation of HDAC6.

12.
Oxid Med Cell Longev ; 2020: 4909103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998438

RESUMO

Direct peritoneal resuscitation with pyruvate (Pyr-PDS) has emerged as an interesting candidate to alleviate injury in diverse organs, while the potential mechanism has yet to be fully elucidated. To explore the effect of autophagy in the spinal cord ischemia-reperfusion (SCIR) injury and the underlying mechanism, we established a model of SCIR in vivo and in vitro. In vivo, male SD rats underwent aortic occlusion for 60 min and then followed by intraperitoneally infused with 20 mL of pyruvate or normal saline for 30 min, and the spinal cords were removed for analysis after 48 h of reperfusion. The functional and morphological results showed that Pyr-PDS alleviated SCIR injury; meanwhile, the expression of autophagy-related genes and transmission electron microscopy displayed autophagy was activated by SCIR injury, and Pyr-PDS treatment could further upregulate the degree of autophagy which plays a protective part in the SCIR injury, while there is no significant difference after treatment with saline. In addition, SCIR injury inhibited expression of PHD2, which results to activate its downstream HIF-1α/BNIP3 pathway to promote autophagy. In the Pyr-PDS, the results revealed PHD2 was further inhibited compared to the SCIR group, which could further activate the HIF-1α/BNIP3 signaling pathway. Additionally, oxygen-glucose deprivation and reoxygenation were applied to SH-SY5Y cells to mimic anoxic conditions in vitro, and the expression of autophagy-related genes, PHD2, and its downstream HIF-1α/BNIP3 pathway showed the same trend as the results in vivo. Besides, IOX2, a specific inhibitor of PHD2 was also treated to SH-SY5Y cells during reoxygenation, in which the result is as same as the pyruvate group. Then, we observed the expression of autophagy-related genes and the HIF-1α signal pathway in the process of reoxygenation; the results showed that as the reoxygenation goes, the expression of the HIF-1α signal pathway and degree of autophagy came to decrease gradually, while treated with pyruvate could maintain autophagy high and stable through keeping PHD2 at a lower level during reoxygenation, and the latter was observed downregulated during reoxygenation process from 0 to 24 hours in a time-effect way. The above results indicated that direct peritoneal resuscitation with pyruvate showed effective protection to ischemia-reperfusion of the spinal cord through activating autophagy via acting on PHD2 and its downstream HIF-1α/BNIP3 pathway.


Assuntos
Morte Celular Autofágica/efeitos dos fármacos , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Ácido Pirúvico/farmacologia , Traumatismo por Reperfusão , Transdução de Sinais/efeitos dos fármacos , Doenças da Medula Espinal , Animais , Modelos Animais de Doenças , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Injeções Intraperitoneais , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Ratos , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Ressuscitação , Doenças da Medula Espinal/enzimologia , Doenças da Medula Espinal/patologia , Doenças da Medula Espinal/prevenção & controle
13.
Artigo em Inglês | MEDLINE | ID: mdl-31931332

RESUMO

A rapid, simple, and generic analytical method that could simultaneously determine 291 undesirable low molecular weight chemical contaminants from different drug families in protein powder, such as veterinary drugs and pesticides, etc, had been developed. This method comprised the extraction with acetonitrile-dimethyl sulfoxide (DMSO), clean-up through dispersive solid phase extraction (D-SPE) and low temperature filtration, and analysis by ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry at multiple-reaction monitoring mode. Acetonitrile-DMSO was more generic than acetonitrile or methanol for the extraction of large-scale organic chemical contaminants with different polarities in protein powder. Most interferences in the extract were eliminated by the combination of D-SPE and low temperature filtration, which simultaneously provided satisfactory recoveries of both hydrophobic and hydrophilic analytes. In particular, besides the purification function, the sorbent of D-SPE also played an important role in grinding samples to improve extraction efficiency during homogenization. This streamlined approach allowed the processes of extraction and the main purification were carried out in one-step, and dramatically reduced sample preparation turnaround times and solvent consumption. For quantification, matrix-fortified calibration curves showed competent linearity for most of the target compounds with linear regression coefficients (r) higher than 0.9900, except for two analytes. The limits of quantification ranged from 0.1 µg/kg to 50 µg/kg, which was usually sufficient to verify the compliance of products with legal tolerances. The average recoveries for spiked protein powder ranged from 65.6% to 142.2% with associated RSD values between 0.5% and 28.5%. For over 90% of the analytes, the recoveries were between 70% and 120% with RSD values in the range of 1%-15%. Applying this method in routine monitoring programs would drastically reduce both effort and time.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Proteínas na Dieta , Resíduos de Drogas/análise , Contaminação de Alimentos/análise , Espectrometria de Massas em Tandem/métodos , Proteínas na Dieta/análise , Proteínas na Dieta/normas , Suplementos Nutricionais/análise , Suplementos Nutricionais/normas , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
Br J Pharmacol ; 177(8): 1865-1880, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31877572

RESUMO

BACKGROUND AND PURPOSE: Cannabis or cannabinoids produce characteristic tetrad effects-analgesia, hypothermia, catalepsy and suppressed locomotion, which are believed to be mediated by the activation of cannabinoid CB1 receptors. Given recent findings of CB2 and GPR55 receptors in the brain, we examined whether these receptors are also involved in cannabinoid action. EXPERIMENTAL APPROACH: We compared Δ9 -tetrahydrocannabinol (Δ9 -THC)-, WIN55212-2-, or XLR11-induced tetrad effects between wild-type (WT) and each genotype of CB1 -, CB2 - or GPR55-knockout (KO) mice and then observed the effects of antagonists of these receptors on these tetrad effects in WT mice. KEY RESULTS: Systemic administration of Δ9 -THC, WIN55212-2 or XLR11 produced dose-dependent tetrad effects in WT mice. Genetic deletion or pharmacological blockade of CB1 receptors abolished the tetrad effects produced by all three cannabinoids. Unexpectedly, genetic deletion of CB2 receptor abolished analgesia and catalepsy produced by Δ9 -THC or WIN55212-2, but not by XLR11. Microinjections of Δ9 -THC into the lateral ventricles also produced tetrad effects in WT, but not in CB1 -KO mice. CB2 -KO mice displayed a reduction in intraventricular Δ9 -THC-induced analgesia and catalepsy. In contrast to CB1 and CB2 receptors, genetic deletion of GPR55 receptors caused enhanced responses to Δ9 -THC or WIN55212-2. Antagonisim of CB1 , CB2 or GPR55 receptors produced alterations similar to those observed in each genotype mouse line. CONCLUSIONS AND IMPLICATIONS: These findings suggest that in addition to CB1 , both CB2 and GPR55 receptors are also involved in some pharmacological effects produced by cannabinoids. CB1 /CB2 , in contrast to GPR55, receptors appears to play opposite roles in cannabinoid action.

15.
J Surg Res ; 248: 98-108, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31877436

RESUMO

BACKGROUND: This study aimed to investigate the role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in protection by peritoneal resuscitation (PR) using pyruvate-peritoneal dialysis solution (PY-PDS) against intestinal injury from hemorrhagic shock (HS) in rats. MATERIALS AND METHODS: Sixty-four rats were assigned to eight groups: group SHAM; group intravenous resuscitation (VR); groups NS, LA, and PY in which the rats were subjected to HS and PR with normal saline (NS), lactate-peritoneal dialysis solution (LA-PDS), and PY-PDS, respectively, combined with VR; and groups DMSO, RPM, and AG490 in which the rats were subjected to HS and VR with pretreatment of dimethyl sulfoxide (DMSO), rapamycin (RPM), and tyrphostin B42 (AG490). RESULTS: At 2 h after HS and resuscitation, the levels of diamine oxidase, 15-F2t-isoprostane, thromboxane B2, and endothelin-1, in the blood and the intestinal mucosal apoptotic index and caspase-3 were lower in groups PY, RPM, and AG490 than in groups VR, NS, LA, and DMSO. Group PY showed lower levels of malondialdehyde and myeloperoxidase and a higher level of superoxide dismutase than groups VR, NS, and LA. Phosphorylated JAK2 and phosphorylated STAT3 levels were lower in groups PY, RPM, AG490, and LA than in groups VR, NS, and DMSO. CONCLUSIONS: The protection mechanism of PR with PY-PDS combined with VR was related to the inhibition of the JAK/STAT signaling pathway during HS and resuscitation. The process might include suppression of oxidative stress, reduction of neutrophil infiltration, regulation of microcirculation, and inhibition of apoptosis.


Assuntos
Enteropatias/prevenção & controle , Ácido Pirúvico/uso terapêutico , Ressuscitação/métodos , Choque Hemorrágico/terapia , Animais , Soluções para Diálise , Avaliação Pré-Clínica de Medicamentos , Enteropatias/etiologia , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismo , Masculino , Ácido Pirúvico/farmacologia , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição STAT/antagonistas & inibidores , Fatores de Transcrição STAT/metabolismo , Choque Hemorrágico/complicações , Transdução de Sinais/efeitos dos fármacos
16.
Biomed Res Int ; 2019: 9296010, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886269

RESUMO

Objective: To explore the conventional and contrast-enhanced ultrasound (CEUS) features of cervical lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) patients postoperatively and analyze its pathological basis. Materials and Methods: Conventional and CEUS were performed in 86 abnormal cervical lymph nodes (ACLNs) from 56 PTC patients who had received thyroidectomy. Then, fine-needle aspiration (FNA) was taken to confirm pathological results, a multivariate analysis was performed to correlate the sonographic features of the CLNM, and then an equation for CLNM was established. Results: Fifty-four lymph nodes were confirmed to be metastasis of PTC by FNA. Intensity at peak time, homogeneity, and color flow patterns, cystic change, or microcalcification and echogenicity were significantly associated with CLNM. Multivariate analysis showed three strongest features (homogeneity, intensity of peak, and cystic change or calcification) to be significantly associated with the evidence of CLNM. Then, the equation was established with the following significant predictive factors: P = 1/1 + exp∑[-3.213 + 2.77 ∗ cystic or calcification + 0.13 ∗ CDFI patterns + 3.65 ∗ homogeneity + 2.43 ∗ intensity at peak time]. Conclusion: Depiction of a heterogeneous hyperenhancement of cervical lymph nodes within CEUS studies and cystic change or microcalcification in conventional ultrasound were identified as predictive for metastatic lymph node invasion, and the equation was more accurate for predicting CLNM compared to single B-mode ultrasound and CEUS feature.


Assuntos
Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Câncer Papilífero da Tireoide/complicações , Neoplasias da Glândula Tireoide/complicações , Tireoidectomia/métodos , Ultrassonografia/métodos , Adulto , Idoso , Calcinose/patologia , Carcinoma Papilar/patologia , Feminino , Humanos , Metástase Linfática/patologia , Vasos Linfáticos/diagnóstico por imagem , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pescoço/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
17.
Biomed Pharmacother ; 118: 109363, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545277

RESUMO

OBJECTIVE: Alveolar epithelial barrier dysfunction in response to inflammatory reaction contributes to pulmonary edema in acute lung injury(ALI).Irisin,a newly-found myokine,exerts the anti-inflammatory effects. This study aims to investigate the protective effects of irisin on lipopolysaccharide (LPS)-induced ALIin vivo and in vitro, and to explore its underlying mechanism. METHODS: Male SD rats and A549 cells were divided into 4 groups: control group, LPS group, Irisin pretreated group, and Irisin/Compound C(a special inhibitor of AMPK)-treated group. The ALI model was established by intravenous injection of LPS in rats, and LPS challenge in A549 cells. Pulmonary specimens were harvested for microscopic examination of the pathological changes, and the expression of AMPK,SIRT1,NF-κB, p66Shc and caspase-3 in lung tissues. The pulmonary permeability were examined by wet/dry lung weight ratio(W/D) and lung permeability index(LPI). The apoptotic index, and the expression of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), monocyte chemoattractant activating protein-1 (MCP-1), tight junctions (occludin,ZO-1) were determined both in lung tissue and A549 cells. RESULTS: Irisin alleviated lung histological changes and decreased pulmonary microvascular permeability in LPS-induced rats. Irisin up-regulated the expression of occludin, ZO-1,AMPK,SIRT1, down-regulated the expression of TNF-α,IL-1ß,MCP-1,NF-κB, p66Shc caspase-3, and decreased the apoptotic index in LPS-induced rats and A549 cells. All these protective effects of irisin could be reversed by Compound C. CONCLUSION: Irisin improved LPS-induced alveolar epithelial barrier dysfunction via suppressing inflammation and apoptosis, and this protective effect might be mediated by activating AMPK/SIRT1 pathways.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Lesão Pulmonar Aguda/fisiopatologia , Epitélio/fisiopatologia , Fibronectinas/uso terapêutico , Pulmão/fisiopatologia , Transdução de Sinais , Sirtuína 1/metabolismo , Células A549 , Lesão Pulmonar Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Epitélio/ultraestrutura , Fibronectinas/farmacologia , Humanos , Inflamação/patologia , Pulmão/patologia , Pulmão/ultraestrutura , Masculino , Permeabilidade , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Regulação para Cima/efeitos dos fármacos
18.
Ultrasound Med Biol ; 45(8): 1924-1932, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31122812

RESUMO

The aim of this study was to analyze the diagnostic performance of contrast-enhanced ultrasound (CEUS) in differentiating between benign and malignant renal masses, with a special emphasis on the value of the pseudocapsule sign. A total of 163 consecutive patients with 163 renal masses were involved. The conventional ultrasonography and CEUS features were assessed. Sensitivity, specificity and the area under the receiver operating characteristic curve (Az) were calculated for qualitative CEUS, and a multivariate analysis was performed to analyze the correlation between the sonographic features and malignancy. Time to peak (TTP) and peak intensity (PI) were compared between benign and malignant renal masses for quantitative CEUS analysis in 72 of 163 patients. Intraclass correlations were calculated for variability in intensity and time parameters between qualitative and quantitative evaluation. Among all qualitative CEUS features, the pseudocapsule sign showed the highest Az (0.777; 95% confidence interval: 0.701-0.853) and yielded the highest sensitivity (67.4%) and specificity (88.0%); multivariate logistic regression analysis showed that the pseudocapsule sign and color Doppler flow imaging patterns were the two strongest independent predictors for malignancy. For quantitative CEUS analysis, higher PI and shorter TTP were found in malignant renal masses than those in benign ones. The Intraclass correlation coefficient values among qualitative and the quantitative assessments were 0.00 for time and 0.03 for intensity. The pseudocapsule sign offered the most efficient performance among all the qualitative and quantitative CEUS features.


Assuntos
Meios de Contraste , Aumento da Imagem/métodos , Neoplasias Renais/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
19.
Ultrasound Med Biol ; 45(8): 2040-2048, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31130409

RESUMO

Superb microvascular imaging (SMI) is an innovative vascular imaging technique for ultrasound (US). Compared with conventional color Doppler imaging (CDI) and power Doppler imaging (PDI), SMI can detect more blood flow in thyroid nodules. In this study, a total of 203 thyroid nodules (160 benign nodules, 43 malignant nodules) in 195 patients were assessed with the Thyroid Imaging Reporting and Data System (TI-RADS) published by the American College of Radiology in 2017) and SMI. With TI-RADS alone, 24 (15.0%), 76 (47.5%), 65 (40.6%) and 39 (24.4%) thyroid nodules were classified as TR2, TR3, TR4 and TR5, respectively. However, with the combination of TI-RADS and SMI, 31 (19.4%), 79 (49.4%), 44 (27.5%) and 49 (30.6%) thyroid nodules were classified as TR2, TR3, TR4 and TR5, respectively. The area under the receiver operating characteristic curves for the combination (0.952) was larger than that for TI-RADS alone (0.883) (Z = 3.478, p = 0.001). The efficiency of TI-RADS alone and the TI-RADS + SMI combination in diagnosing thyroid nodules was determined for all except TR2 nodules. Although no significant differences between the methods were observed for TR3 and TR5 thyroid nodules (p > 0.05), the diagnostic efficiency of TI-RADS + SMI for TR4 thyroid nodules was higher than that of TI-RADS alone for TR4 nodules (p < 0.05). This study indicated that the vascularity of thyroid nodules can be well characterized using SMI, and the combined use of gray-scale US and SMI can improve the diagnostic performance of TI-RADS for TR4 thyroid nodules.


Assuntos
Sistemas de Informação em Radiologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Glândula Tireoide/diagnóstico por imagem , Adulto Jovem
20.
Clin Endocrinol (Oxf) ; 91(1): 201-208, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31004514

RESUMO

OBJECTIVE: To evaluate the value of shear wave elastography (SWE) in avoiding repeat fine-needle aspiration of thyroid nodules with nondiagnostic and undetermined cytology. METHODS: A total of 232 thyroid nodules with nondiagnostic (n = 132) and undetermined (n = 100) cytology underwent ultrasound (US) and SWE, followed by repeat ultrasound (US)-guided fine-needle aspiration cytology (FNAC). The final diagnosis was based on cytological or pathological findings. The US and SWE characteristics of benign and malignant nodules were compared using the χ2 -test. The receiver operating characteristic (ROC) curves of the thyroid imaging reporting and data system (TI-RADS) categories from the US and the EMean and ESD from the SWE were graphed, and the areas under the curves (AUCs) were compared using a Z test. RESULTS: There were significant differences between the benign and malignant nodules in terms of the echogenicity, shape, margin, calcification and TI-RADS categories (all P < 0.05). The differences were significant between the malignant and benign nodules for EMean [(34.57 ± 14.81) kPa vs. (19.18 ± 7.09) kPa] and ESD [(13.68 ± 13.01) kPa vs. (3.97 ± 2.58) kPa] (both P < 0.001). Though the difference in the AUCs of EMean (0.864) and ESD (0.876) was not significant (P = 0.745), they both had higher diagnostic performances in comparison with TI-RADS categories (0.762) (all P < 0.05). Moreover, ESD attained a sensitivity of 100% with a relatively higher specificity of 49.75% when its cut-off value was 3.3 kPa. CONCLUSIONS: Shear wave elastography is a promising imaging method for reducing repeat FNAC for benign thyroid nodules with nondiagnostic and undetermined cytology when using ESD as an index.


Assuntos
Biópsia por Agulha Fina/métodos , Técnicas de Imagem por Elasticidade/métodos , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA