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1.
J Ethnopharmacol ; 264: 113021, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32479885

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is an outcome of many chronic liver diseases and often results in cirrhosis, liver failure, and even hepatocarcinoma. Xiaoyaosan decoction (XYS) as a classical Traditional Chinese Medicine (TCM) formula is used to liver fibrosis in clinical practice while its mechanism is unclear. AIM OF THE STUDY: The aim of this study was to investigate the anti-fibrosis effect of XYS and to explore the molecular mechanisms by combining network pharmacology and transcriptomic technologies. MATERIALS AND METHODS: The carbon tetrachloride (CCl4)-induced liver fibrosis rat were treated with three doses of XYS. The liver fibrosis and function were evaluated by histopathological examination and serum biochemical detection. The fibrosis related protein a-SMA and collagen I were assessed by Western blot. Different expressed genes (DEGs) between XYS-treated group and model group were analyzed. The herb-component-target network was constructed combined the network pharmacology. The predict targets and pathways were validated by in vitro and in vivo experiments. RESULTS: With XYS treatment, the liver function was significantly improved, and fibrotic changes were alleviated. The a-SMA and collagen I expression levels in the liver were also decreased in XYS-treated rats compared with CCl4 model rats. 108 active components and 42 targets from 8 herbs constituted herb-compound-target network by transcriptomics and network pharmacology analysis. The KEGG pathway and GO enrichment analyses showed that the FoxO, TGFß, AMPK, MAPK, PPAR, and hepatitis B and C pathways were involved in the anti-fibrosis effects of XYS. In the liver tissues, p-FoxO3a and p-Akt expression levels were significantly increased in the CCl4 model group but decreased in the XYS-treated group. The TGFß1/Smad pathway and Akt/FoxO3 pathway were verified in LX2 cells by inhibiting phosphorylation of Smad3 and Akt activity, respectively. CONCLUSIONS: Our findings suggested that XYS markedly alleviated CCl4-induced liver fibrosis in histopathological and serum liver function analyses, and this effect may occur via the TGFß1/Smad and Akt/FoxO signaling pathways.

2.
J Ethnopharmacol ; 265: 113302, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32860893

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Laminaria japonica, a brown seaweed, has been used in Traditional Chinese Medicine (TCM) to treat a variety of diseases including lung cancer. AIM OF THE STUDY: To demonstrate the effects of Fucoxanthin (FX), a major active component extracted from Laminaria japonica on metastasis and Gefitinib (Gef) sensitivity in human lung cancer cells both in vitro and in vivo. MATERIALS AND METHODS: Invasion and migration of lung cancer cells were detected using the wound healing assay and transwell assay. Epithelial-to-mesenchymal transition (EMT) factors and PI3K/AKT/NF-κB pathways were analyzed by western blotting. RNA interference (RNAi) technology was used to silence TIMP-2 gene expression in A549 cells. The anti-metastatic effect of FX was evaluated in vivo in an experimental lung metastatic tumor model. On the other hand, cell counting kit-8 assay was used to study the cell viability of human lung cancer PC9 cells and Gef resistant PC9 cells (PC9/G) after Gef, FX or FX combined with Gef treatment. PC9 xenograft model was established to explore the anti-tumor effect of FX or combined with Gef. Immunohistochemistry staining assay and immunofluorescence staining assay were used to reveal the effects of FX on lung cancer cell proliferation and apoptosis. RESULTS: FX was able to significantly inhibit lung cancer cells migration and invasion in vitro. FX suppressed the expressions of Snail, Twist, Fibronectin, N-cadherin, MMP-2, PI3K, p-AKT and NF-κB, and increased the expression of TIMP-2. Furthermore, knockdown of TIMP-2 attenuated FX-mediated invasion inhibition. Additionally, we demonstrated that FX inhibited lung cancer cells metastasis in vivo. The anti-metastatic effects of FX on lung cancer cells might be attributed to inhibition of EMT and PI3K/AKT/NF-κB pathway. We further demonstrated that the anti-tumor activity of FX was not only limited to the drug sensitive cell lines, but also prominent on lung cancer cells with Gef resistant phenotype. Furthermore, in vivo xenograft assay confirmed that FX inhibited tumor growth and enhanced the sensitivity of lung cancer cells to Gef and this effect may be due to inhibition of tumor cell proliferation and activation of apoptosis. CONCLUSION: Collectively, our findings suggested that FX suppresses metastasis of lung cancer cells and overcomes EGFR TKIs resistance. Thus, FX is worthy of further investigation as a drug candidate for the treatment of lung cancer.

3.
Biomaterials ; : 120455, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33162174

RESUMO

The rapid development of nanotechnology has triggered the emerging of tremendous theranostic nanoplatforms for combating cancers. Silicene, as an emerging two-dimensional (2D) material, has been recently explored as therapeutic agent due to their desirable biodegradation and strong photothermal-conversion performance. However, the rational design of silicene-based composites for further exerting multifunctional medical applications is still highly challenging. Herein, we report on the construction of silicene-based silicene@Pt composite nanosheets for computed tomography (CT)/photoacoustic (PA) imaging-guided dual-sensitized radiotherapy combined with photonic tumor hyperthermia, which has been achieved by a seed-growth approach to in situ grow Pt components onto silicene nanosheets' surface. Especially, by functionalization of Pt components, these nanosheets could act as both contrast agents for CT imaging and dual radio-sensitizing agents for radiotherapy, which could deposit Pt-involved radiation energy (sensitized therapeutic process I) and overcome hypoxia-associated radio-resistance by Pt-catalytic O2 generation from overexpressed H2O2 within the tumor microenvironment (sensitized therapeutic process II). The strong photothermal-conversion performance of silicene nanosheets not only endowed silicene@Pt composite nanosheets with photoacoustic imaging property, but also realized the photonic tumor hyperthermia and achieved a combined therapeutic effect with radiotherapy. This work not only broadens the biomedical applications of silicene, but also develops functionalization strategies of silicene for versatile biomedical applications.

4.
Clin Imaging ; 70: 136-141, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33161342

RESUMO

OBJECTIVES: We retrospectively analyzed data of the BECOME trial to investigate whether serial administration of triple-dose (3-dose) gadopentetate dimeglumine would result in the development of T1 signal-to-noise (S/N) changes in the cranial diploic space and whether S/N changes correlated with on-study hypophosphatemia. METHODS: Signal intensity analysis was performed on the first year's data of the BECOME trial using 3-dose Gd (14 months, maximum number of doses, 39, mean: 36). Routine blood and urine tests were obtained each month for safety monitoring. Linear mixed regression modeling with random intercept was used to analyze monthly signal-to-noise ratio (S/N = Bone/Air) using an ROI of the diploic space created from T2W images and overlaid on T1FS (T1 fat-saturated) images. Incidence of phosphate abnormalities was analyzed using the general estimation equation; correlation of phosphate and S/N change was achieved with type 3 test of fixed effects. RESULTS: Cranial diploic space T1FS S/N increased over 14 months: S/N = 0.039 mean monthly increase (S.E. 0.008; p < 0.0001). Subjects with consistently normal phosphate levels (n = 32) experienced more of a S/N increase than patients with at least one episode of hypophosphatemia (n = 35) (0.057 vs. 0.023, respectively, p = 0.037). Those with moderate hypophosphatemia demonstrated no significant S/N increase. CONCLUSION: Monthly administration of 3-dose gadopentetate dimeglumine is associated with development of increased S/N on T1FS imaging in the cranial diploic space, suggesting Gd retention in bone. Our data suggests MRI could be used as a noninvasive method of tracking Gd retention in bone, which was more pronounced in patients with normal phosphate levels.

5.
Reprod Biol Endocrinol ; 18(1): 119, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225937

RESUMO

BACKGROUND: Endometriosis is a benign gynecological disease with obviously feature of estrogen-dependence and inflammatory response. The applications of primary endometriotic stromal cells in research of endometriosis are restricted for short life span, dedifferentiation of hormone and cytokine responsiveness. The objective of this study was to establish and characterize immortalized human endometriotic stromal cells (ihESCs). METHODS: The endometriotic samples were from a patient with ovarian endometriosis and the primary endometriotic stromal cells were isolated from the endometriotic tissues. The primary cells were infected by lentivirus to establish telomerase reverse transcriptase (hTERT)-induced immortalized cells. Quantification of mRNA and proteins was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot. CCK-8 assay and EdU labeling assay were assigned to assess the growth of ihESCs. Karyotype assay was performed to detect the chromosomes of ihESCs. Colony formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities. RESULTS: ihESCs continuously overexpressed hTERT via infection of lentivirus and significant extended the life span reaching 31 passages. The morphology, proliferation and karyotype of ihESCs remained unchanged. The expression of epithelial-mesenchymal transition (EMT) markers, estrogen-metabolizing proteins and estrogen/progesterone receptors (ERs and PRs) were unaltered. Furthermore, the treatment of estrogen increased the proliferation and EMT of ihESCs. Lipopolysaccharides (LPS) and IL-1ß remarkably induced inflammatory response. The clonogenesis ability of ihESCs was consistent with primary cells, which were much lower than Ishikawa cells. In addition, nude mouse tumorigenicity assay demonstrated that ihESCs were unable to trigger tumor formation. CONCLUSION: This study established and characterized an immortalized endometriotic stromal cell line that exhibited longer life span and kept the cellular morphology and physiological function as the primary cells. The immortalized cells remained normal feedback to estrogen and inflammatory response. Moreover, the immortalized cells were not available with tumorigenic ability. Therefore, ihESCs would be serviceable as in vitro cell tool to investigate the pathogenesis of endometriosis.

6.
J Biosci Bioeng ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33077360

RESUMO

Quorum sensing (QS) exists in bacteria to communicate with each other and regulate group behaviors in a cell density-dependent manner, which uses signal molecule autoinducer-2 (AI-2) to intra- and inter-species communication. Effects of exogenous AI-2 on biofilm formation and environmental tolerance in Lactobacillus plantarum are the focus of this review. The responses to the exogenous AI-2 cross multiple physiological metabolic behaviors involving the bacteria growth, morphological characterization, biofilm development, extracellular polysaccharides (EPS) amount and related genes expression as well as the environmental stresses tolerance. The cell surface was smoother in the AI-2 supplemented treatments than without AI-2. Meanwhile, AI-2 had ability to promote the growth and formation of biofilm by increasing the yield of EPS, the main components of biofilm. The changes in lamC and ftsH gene expression point to altered regulation for hydrolysis process of polysaccharides as well as the potential for enhanced biofilm formation. The presence of AI-2 also significantly improved (p < 0.01) the tolerance of bile salts in L. plantarum, but the same results did not appear in acid tolerance. In conclusion, AI-2 supplementation could improve the biofilm formation and bile salts tolerance in L. plantarum, and this effect was likely modulated by facilitating EPS production and suppression polysaccharides hydrolysis.

7.
Environ Int ; 145: 106168, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33049548

RESUMO

BACKGROUND: Particulate pollution is currently regarded as a severe environmental problem, which is intimately linked to reductions in air quality and human health, as well as global climate change. OBJECTIVE: Accurately identifying the key factors that drive air pollution is of great significance. The temporal and spatial heterogeneity of such factors is seldom taken into account in the existing literature. METHOD: In this study, we adopted a geographically and temporally weighted regression model (GTWR) to explore the direction and strength of the influences of natural conditions and socioeconomic issues on the occurrence of PM2.5 pollutions in 287 Chinese cities covering the period 1998 to 2015. RESULT: Cities with serious PM2.5 pollution were discovered to mainly be situated in northern China, whilst cities with less pollution were shown to be located in southern China. Higher temperature and wind speed were found to be able to alleviate air pollution in the country's southeast, where enhanced precipitation was also shown to reduce PM2.5 concentrations; whilst in southern and central and western regions, precipitation and PM2.5 concentrations were positively correlated. Increased relative humidity was found to reinforce PM2.5 concentration in southwest and northeast China. Furthermore, per capita GDP and population density were shown to intensify PM2.5 concentrations in northwest China, inversely, they imposed a substantial adverse effect on PM2.5 concentration levels in other areas. The amount of urban built-up area was more positively associated with PM2.5 concentration levels in southeastern cities than in other cities in China. CONCLUSION: PM2.5 concentrations conformed to a series of stages and demonstrated distinct spatial differences in China. The associations between PM2.5 concentration levels and their determinants exhibit obvious spatial heterogeneity. The findings of this paper provide detailed support for regions to formulate targeted emission mitigation policies.

8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1570-1577, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067956

RESUMO

AbstractObjective:To investigate the expression of miR-215 and KDM1B in DLBCL patients, and to analysis its clinical significance. METHODS: Fifty patients with DLBCL treated in our hospital were selected as DLBCL group, and 30 cases of reactive proliferative lymphadenitis(RPL) were selected as controls. RQ-PCR was used to detect the expression level of miR-215, and immunohistochemistry was used to detect the expression of KDM1B protein. The expression of miR-215 and KDM1B in patients with different clinical characteristics and the survival rate of patients with different expression of miR-215 and KDM1B was compared. miR-215 mimics was transfected into SU-DHL-4 cells. Cell proliferation was detected by CCK-8. Cell apoptosis was measured by flow cytometry. The expression of KDM1B protein was detected by Western blot. RESULTS: The expression of miR-215 in DLBCL patients was significantly lower than that in control group, and the positive expression of KDM1B protein was higher, the difference was statistically significant(P<0.01). Spearman rank correlation analysis showed that the expression of miR-215 negatively correlated with KDM1B (r=-0.751,P<0.05). There was significant correlation of miR-215, KDM1B expression with symptoms of B,Serum level of LDH, International Prognostic Index(IPI), Ann Arbor stage,Tumor size, respectively in patients(P<0.05). Kaplan-Meier showed that 5-year overall survival rate of patients with high miR-215 expression was significantly longer than that with low miR-215 expression (P=0.013). The 5-year survival rate of the patients with high positive KDM1B expression was significantly lower than that with low positive expression(P=0.024). KDM1B protein was suppressed by the transfection of miR-215 mimics for 72 h, the cell proliferation rate in miR-215 mimics group was significantly lower than that in control group and NC mimics group (P<0.05), but cell apoptotic rate of miR-215 mimics were significantly higher(P<0.05). The expression of KDM1B protein was significantly lower than that in control and NC group(P<0.05). CONCLUSION: There are low expression of miR-215 and high expression of KDM1B protein in patients with DLBCL, suggesting that they may be the diagnostic and prognostic indicators of DLBCL. miR-215 can directly target KDM1B to inhibit cell growth and induce apoptosis.


Assuntos
Linfoma Difuso de Grandes Células B , MicroRNAs , Apoptose , Proliferação de Células , Humanos , Oxirredutases N-Desmetilantes , Prognóstico
9.
Artigo em Inglês | MEDLINE | ID: mdl-33025567

RESUMO

Immobilization of enzyme based on combination of adsorption and cellulose derivative membrane coating was established in this work for the first time. Laccase, a commonly used enzyme in varied fields, was chosen as the model enzyme to demonstrate this method. After investigating operational conditions, the optimal process was obtained as follows: diatomite or HPD-417 as the adsorption carrier, 0.5% (w/v) methylcellulose (40,000~50,000) acetone solution as the coating solution, 0.75% (w/v) polyethylene glycol or maltose as the protective agent, and drying at 4 °C for 9 h. Under the optimal conditions, the residual activities of diatomite and HPD-417 immobilized laccase reached 99.33% and 94.15%, respectively. The study on properties showed that the immobilized laccases held high pH tolerance and thermal stability. The immobilized laccases were further applied to the indigo decolorization and 2, 4-dichlorophenol degradation. They showed high catalytic efficiency and could be reused for several batches. On the whole, the immobilization method developed in this work can effectively avoid the inactivation of laccase during immobilization and improve the stability of immobilized laccase. The laccase immobilized by this method shows obvious potential for environmental governance.

10.
Arterioscler Thromb Vasc Biol ; 40(12): 2922-2940, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32998518

RESUMO

OBJECTIVE: In patients with peripheral artery disease, blockages in arterioles <1 mm cannot be treated surgically, and there are currently few effective medicines. Studies have shown that inflammation in ischemic tissue is related to injury recovery and angiogenesis, but insufficient attention has been paid to this area. Studies have suggested that HMGB1 (high mobility group protein 1), which is released by ischemic tissue, promotes angiogenesis, but the mechanism is not entirely clear. In this study, we tested the internalization of HMGB1 in endothelial cells and investigated a novel proangiogenic pathway. Approach and Results: Using green fluorescent protein-tagged HMGB1 to stimulate endothelial cells, we demonstrated HMGB1 internalization via dynamin and RAGE (receptor for advanced glycation end products)-dependent signaling. Using a fluorescence assay, we detected internalized protein fusion to lysosomes, followed by activation of CatB (cathepsin B) and CatL (cathepsin L). The latter promoted the release of VEGF (vascular endothelial growth factor)-A and endoglin and upregulated the capacities of cell migration, proliferation, and tube formation in endothelial cells. We identified that the cytokine-induced fragment-a key functional domain in HMGB1-mediates the internalization and angiogenic function of HMGB1. We further confirmed that HMGB1 internalization also occurs in vivo in endothelial cells and promotes angiogenesis in mouse femoral artery ligation. CONCLUSIONS: In this study, we identified a novel pathway of HMGB1 internalization-induced angiogenesis in endothelial cells. This finding sheds light on the regulatory role of inflammatory factors in angiogenesis through cell internalization and opens a new door to understand the relationship between inflammation and angiogenesis in ischemic diseases.

11.
Sci Rep ; 10(1): 16712, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009495

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1035-1043, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051416

RESUMO

OBJECTIVES: Long non-coding RNAs (lncRNAs) were involved in the development and regulation of necrotizing enterocolitis (NEC) in premature infants. To investigate the changes of lncRNA expression profile in intestinal tissues of NEC for its possible mechanisms. METHODS: Intestinal samples were collected from 11 patients with NEC who needed surgery(the NEC group), and 7 from neonatal non-NEC patients with surgery (the Control group).LncRNA's changes in intestinal samples (3 in the Control group and 3 in the NEC group) were analyzed with high-throughput sequencing.Part of the remaining samples were detected by real-time polymerase chain reaction (real-time PCR), and the results were used to validate the results of high-throughput sequencing. Gene Ontology (GO) analysis and KEGG signaling pathway analysis were performed on differentially expressed genes. RESULTS: There were 5 257 different lncRNAs between the control group and the NEC group. The results of up-regulated lncRNAs (NONHSAG008675.3, NONHSAG020715.2, NONHSAG038187.2) and down-regulated lncRNA (NONHSAG028744.3) were confirmed to be consistent with the results of high-throughput sequencing. Expressions of DUOX2, IL-6, TNF, and SAA1 were up-regulated in intestinal tissues of NEC. GO analysis showed that the different lncRNAs were involved in regulation of stimulation, molecular junction and function, and signal transduction and transcription. KEGG analysis identified mainly biological pathways involved in inflammatory bowel disease, PI3K-Akt, NF-κB, etc. CONCLUSIONS: LncRNAs might be involved in the pathogenesis of NEC and the inflammation-related lncRNAs may be one of the key factors.


Assuntos
Enterocolite Necrosante , RNA Longo não Codificante , Animais , Oxidases Duais , Enterocolite Necrosante/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Intestinos , Fosfatidilinositol 3-Quinases , RNA Longo não Codificante/genética
13.
Biosci Rep ; 40(10)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-32969465

RESUMO

BACKGROUND: Despite the prominent development of medical technology in recent years, the prognosis of non-small cell lung cancer (NSCLC) is still not optimistic. It is crucial to identify more reliable diagnostic biomarkers for the early diagnosis and personalized therapy of NSCLC and clarify the molecular mechanisms underlying NSCLC progression. METHODS: In the present study, bioinformatics analysis was performed on three datasets obtained from the Gene Expression Omnibus to identify the NSCLC-associated differentially expressed genes (DEGs). Immunohistochemistry-based tissue microarray of human NSCLC was used to experimental validating the potential targets obtained from bioinformatics analysis. RESULTS: By using protein-protein interaction (PPI) network analysis, Kaplan-Meier plotter, and Gene Expression Profiling Interactive Analysis, we selected 40 core DEGs for further study. Then, a re-analysis of 40 selected genes via Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that nine key genes involved in the cell cycle and p53 signaling pathway participated in the development of NSCLC. Then, we checked the protein level of nine key genes by semi-quantitative of IHC and checked the distribution at a single-cell level. Finally, we validated dual-specificity protein kinase TTK as a biomarker for prognosis in a tissue microarray. High TTK expression associated with a higher histological stage, advanced TNM stage, high frequency of positive lymph nodes, and worse 5-year overall survival. CONCLUSIONS: We found nine key genes were enriched in the cell cycle and p53 signaling pathway. TTK could be considered as a potential therapeutic target and for the prognosis biomarker of NSCLC. These findings will provide new insights for the development of individualized therapeutic targets for NSCLC.

15.
Expert Opin Drug Deliv ; : 1-17, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32954856

RESUMO

INTRODUCTION: Platinum chemotherapy is widely used in first-line treatment of patients with various cancers. PD-1/PD-L1 inhibitors have shown efficacy in several cancers, and the combination of platinum-based chemotherapy and PD-1/PD-L1 inhibitors has gradually become the focus of attention. Recently, the combination therapy has exhibited significant effects in preclinical models and clinical trials. AREAS COVERED: This review summarizes preclinical and clinical studies of the combination therapy in various cancers, and further explores mechanisms of the treatment. Furthermore, exploration of the mechanism demonstrates that the combination therapy plays a combination role in two ways. On the one hand, the positive effects of platinum-based chemotherapy on immunomodulation can be harnessed to increase the sensitivity of tumor cells to PD-1/PD-L1 inhibitors. On the other hand, platinum-based chemotherapy may upregulate PD-L1 expression in tumor tissue and exert a negative immunomodulatory effect, which can be counteracted by PD-1/PD-L1 inhibitors through their action pathway. What's more, different types of platinum-based chemotherapy exert different immunomodulation properties. EXPERT OPINION: This review describes a potential for the combination of PD-1/PD-L1 inhibitors and novel nanoparticles composed of platinum-loaded complex to yield positive effects in a wide range of doses, thus achieving higher therapeutic effects and lower side effects. ABBREVIATIONS: Treg: regulatory T cell; MDSC: myeloid-derived suppressor cell; TAM: tumor-associated macrophage; IL: interleukin; PD-1: programmed cell death protein-1; PD-L1: programmed death-ligand-1; NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer; HNSCC: head and neck squamous cell cancer; ICD: immunogenic cell death; TME: tumor microenvironment; CTLs: cytotoxic T lymphocytes; TCR: T cell receptor; MHC class 1: major histocompatibility complex class 1; DC: dendritic cell; APC: antigen-presenting cell; PD-L2: programmed death-ligand-2; STAT6: signal transducers and activators of transcription 6; PLG: poly (L-glutamic acid); mPEG: methoxy poly (ethylene glycol); LLC1: Lewis lung carcinoma 1; PI3K: phosphoinositide 3-kinase; AKT: protein kinase B; MOC1: mouse oral cancer 1; cGAS: cyclic guanosine monophosphate-adenosine monophosphate synthase; STING: stimulator of interferon genes; FDA: food and drug administration; cHL: classical Hodgkin's lymphoma; PMBCL: primary mediastinal large B-cell lymphoma; HCC: hepatocellular carcinoma; MCC: merkel cell carcinoma; RCC: renal cell carcinoma; ORR: overall response rate; OR: overall response; OS: overall survival; PFS: progression-free survival; vs: versus; EFGR: epidermal growth factor receptor; ALK: anaplastic lymphoma kinase; ES: extensive stage; CPS: combined positive score; DOR: duration of response; ITT: intention to treat; NMPA: national medical products administration; TKI: tyrosine kinase inhibitor; NPC: nasopharyngeal cancer; DLT: dose-limiting toxicity; MTD: maximum tolerated dose; TNBC: triple-negative breast cancer; GC: gastric cancer; GEJC: gastroesophageal junction carcinoma; DCR: disease control rate; BTC: biliary tract cancer; TTR: time to response; PR: partial response; SD: stable disease; PD: progressive disease; IC50: half maximal inhibitory concentration; IFN: interferon; HLA: human leukocyte antigen; NK: natural killer cell; M6PR: mannose-6-phosphate receptor; GrzB: granzyme B; TNF: tumor necrosis factor.

16.
J Psychosom Res ; 137: 110231, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32889478

RESUMO

OBJECTIVE: To perform an updated and comprehensive meta-analysis on the risks of adverse perinatal outcomes in children whose mothers received antidepressants during pregnancy. METHODS: A systematic literature search of several databases was conducted through December 2018 to identify relevant studies. Risk estimates and their corresponding 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Subgroup and sensitivity analyses were performed to explore the source of heterogeneity and test the robustness. RESULTS: Forty-eight cohort and 6 case-control studies were included. In cohort studies, children whose mothers received antidepressants during pregnancy had higher risks of preterm birth (RR = 1.62, 95% CI: 1.37, 1.90), low birth weight (RR = 1.37, 95% CI: 1.04, 1.80), and admissions to neonatal intensive care unit (RR = 1.60, 95% CI: 1.38, 1.85) when compared with children born by depressed but untreated pregnant women. The risks of spontaneous abortions (RR = 1.49, 95% CI: 1.29, 1.73), large for gestational age (RR = 1.11, 95% CI: 1.03, 1.20), stillbirths (RR = 1.16, 95% CI: 1.02, 1.32), low Apgar score at 5 min (RR = 1.91, 95% CI: 1.42, 2.56), and neonatal convulsions (RR = 1.97, 95% CI: 1.56, 2.48) increased in children whose mothers received antidepressants during pregnancy when compared with children born by healthy pregnant women. CONCLUSION: Compared with children whose mothers did not receive antidepressants during pregnancy, children whose mothers received antidepressants during pregnancy had increased risks of adverse perinatal outcomes. Further research on the dose of antidepressants is needed.

17.
Invest Radiol ; 55(10): 629-635, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32898355

RESUMO

OBJECTIVES: Gadolinium deposition is widely believed to occur, but questions regarding accumulation pattern and permanence remain. We conducted a retrospective study of intracranial signal changes on monthly triple-dose contrast-enhanced magnetic resonance imaging (MRI) examinations from the previously published Betaseron vs. Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints Trial (N = 67) to characterize the dynamics of gadolinium deposition in several deep brain nuclei and track persistence versus washout of gadolinium deposition on long-term follow-up (LTFU) examinations (N = 28) obtained approximately 10 years after enrollment in the Betaseron vs. Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints Trial. MATERIALS AND METHODS: Using T2 and proton density images and using image analysis software (ITK-SNAP), manual regions of interest were created ascribing boundaries of the caudate nucleus, dentate nucleus, globus pallidus, pulvinar, putamen, white matter, and air. Intensity analysis was conducted on T1-weighted fat-saturated (fat-sat) images using the FSL package. A linear rigid-body transform was calculated from the fat-sat image at each target time point to the region of interest segmentation reference time point fat-sat image. Serial MRI signal was analyzed using linear mixed regression modeling with random intercept. Annual MRI signal changes including LTFU scans were assessed with t test. RESULTS: During monthly scanning, all gray matter structures demonstrated a significant (P < 0.0001) increase in contrast-to-noise ratio. Yearly changes in deposition showed distinctive patterns for the specific nucleus: globus pallidus showed complete retention, pulvinar showed partial washout, while dentate, caudate, and putamen returned to baseline (ie, complete washout). CONCLUSIONS: Monthly increased contrast-to-noise ratio in gray matter nuclei is consistent with gadolinium deposition over time. The study also suggests that some deep gray matter nuclei permanently retain gadolinium, whereas others demonstrate washout of soluble gadolinium.

19.
J Sci Food Agric ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32869870

RESUMO

BACKGROUND: Ginkgotoxin including 4'-O-methylpyridoxine (MPN) and MPN-5'-glucoside (MPNG) is responsible for Ginkgo seed food poisoning. The purpose of the work reported was to prepare detoxified Ginkgo seed powder and at the same time to retain the nutritional and functional components of Ginkgo seed powder to the maximum extent. RESULTS: Resin adsorption technology was firstly employed to remove ginkgotoxin from water extract of Ginkgo seed powder. Under optimal conditions, the adsorption efficiency of the optimal resin for MPN could reach 100%, and that for MPNG could only reach 85.4 ± 0.93%. Resin adsorption alone could not effectively remove MPN and MPNG simultaneously. Endogenous enzymatic hydrolysis was next attempted to transform MPNG to MPN. MPNG could be completely hydrolyzed to MPN by endogenous enzyme(s) at 40 °C and pH 5.0 in 180 min. Ginkgotoxin only in the form of MPN in the enzymatic hydrolysate was then adsorbed with resin and the conditions were statistically optimized. The adsorption efficiency of MPN reached 98.89 ± 0.99% under the optimized conditions. CONCLUSIONS: Removal of ginkgotoxin by combining endogenous enzymatic hydrolysis with resin adsorption could preserve the main nutritional and functional components of Ginkgo seed powder to the most extent, and did not change its main characteristics. The ginkgotoxin removal method developed in this work is a relatively simple and efficient approach. © 2020 Society of Chemical Industry.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32924999

RESUMO

OBJECTIVES: To evaluate the efficacy of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in differential diagnosis of sclerosing adenosis (SA) from malignance and investigate the correlated features with pathology. METHODS: We retrospectively enrolled 103 pathologically confirmed SA. All lesions were evaluated with conventional US while 31 lesions with CEUS. Lesions were divided into SA with or without benign lesions (Group 1, n = 81) and SA with malignancy (Group 2, n = 22). Performance of two methods were analyzed. The ultrasonographic characteristics were compared between two groups with Student's t-test for measurement and chi-squared or Fisher's exact test for count data. RESULTS: There were 22 lesions complicated with malignancy, and the mean age of Group 2 was higher than Group 1 (55.27 vs. 41.57, p <  0.001). The sensitivity, specificity and accuracy of conventional US and CEUS were 95.45%, 46.91%, 57.28% and 100%, 62.5%, 70.97%. Angularity (p <  0.001), spicules (p = 0.023), calcification (p = 0.026) and enlarged scope (p = 0.012) or crab claw-like enhancement (p = 0.008) in CEUS were more frequent detected in SA with malignancy. CONCLUSIONS: Though CEUS showed an improved accuracy, the performance of ultrasound in the diagnosis of SA was limited. Awareness and careful review of the histopathologically related imaging features can be helpful in the diagnosis of SA.

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