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1.
Oncogene ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042113

RESUMO

Aiming to identify immune molecules with a novel function in cancer pathogenesis, we found the cluster of differentiation 177 (CD177), a known neutrophil antigen, to be positively correlated with relapse-free, metastasis-free, or overall survival in breast cancer. In addition, CD177 expression is correlated with good prognosis in several other solid cancers including prostate, cervical, and lung. Focusing on breast cancer, we found that CD177 is expressed in normal breast epithelial cells and is significantly reduced in invasive cancers. Loss of CD177 leads to hyperproliferative mammary epithelium and contributes to breast cancer pathogenesis. Mechanistically, we found that CD177-deficiency is associated with an increase in ß-catenin signaling. Here we identified CD177 as a novel regulator of mammary epithelial proliferation and breast cancer pathogenesis likely via the modulation of Wnt/ß-catenin signaling pathway, a key signaling pathway involved in multiple cancer types.

2.
Fitoterapia ; 142: 104489, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32004654

RESUMO

Influenza virus is one of the most widespread infectious diseases in the world. It poses a serious public health threat to humans. With the emergence of drug-resistant virus strains, antiviral drugs are urgently needed to control virus transmission and disease progression. In this study, three main active substances-curcumol, curdione and germacrone-were isolated from the traditional Chinese medicine zedoary. They inhibited the replication of influenza A (H1N1) virus in a dose-dependent manner. After treatment with these compounds, the expression of viral protein and RNA synthesis were inhibited. In vivo, these compounds also reduced H1N1-induced lung damage and the load of virus in serum as well as whole blood cells. In a proteomic analysis, after treatment with germacrone, the expression of antiviral protein and the amount of intracellular virus were significantly reduced, further proving that germacrone can inhibit viral replication. Our experiments have shown that curcumol, curdione and germacrone can inhibit the replication of H1N1 virus; in particular, germacrone shows potential both in vitro and in vivo as a therapeutic drug.

3.
Environ Res ; 182: 109103, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31918316

RESUMO

BACKGROUND: Orofacial clefts (OFCs) are common kind of congenital malformations. The teratogenicity of uranium (U) has been documented in animal study that maternal exposure to U can increase incidence of external malformations including cleft palate. However, there is limited evidence of the association of in utero exposure to U with OFCs risk in humans. OBJECTIVE: This study aimed to investigate the association between in utero exposure to U and the risk of OFCs and its subtypes. METHOD: All subjects were from a case-control study in Shanxi Province, northern China. Eighty-four OFCs cases and 142 healthy controls were included in this study. We used U concentration in umbilical cord as biomarkers to represent intrauterine exposure, which was detected by inductively coupled plasma mass spectrometry. Unconditional logistic regression was used to investigated the association between U level and the risk of OFCs and its subtypes. RESULTS: The median of U concentration in umbilical cord is 0.745 ng/g in case group and 0.455 ng/g in control group. When the U concentration was divided into two categories, high level of U exposure increased the risk of OFCs (OR: 2.08, 95% CI: 1.13-3.86) and its subtype cleft lip with cleft palate (CLP) (OR: 2.72, 95% CI: 1.21-6.14). When divided into three categories, high level of U elevated the risk for OFCs (OR: 2.40, 95% CI: 1.14-5.06) and CLP (OR: 3.04, 95% CI: 1.20-7.74). Meanwhile, a dose-response relationship between the U concentration and the risk of total OFCs (P for trend = 0.009) and CLP (P for trend = 0.007) was found. CONCLUSION: Our study found that in utero exposure to high level of U was associated with increased risk of OFCs and its subtype CLP.

4.
J Phys Chem Lett ; : 1261-1267, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31971388

RESUMO

Singlet fission is believed to improve the efficiency of solar energy conversion by breaking up the Shockley-Queisser thermodynamic limit. Understanding of triplet excitons generated by singlet fission is essential for solar energy exploitation. Here we employed transient absorption microscopy to examine dynamical behaviors of triplet excitons. We observed anisotropic recombination of triplet excitons in hexacene single crystals. The triplet exciton relaxations from singlet fission proceed in both geminate and non-geminate recombination. For the geminate recombination, the different rates were attributed to the significant difference in their related energy change based on the Redfield quantum dissipation theory. The process is mainly governed by the electron-phonon interaction in hexacene. On the other hand, the non-geminate recombination is of bimolecular origin through energy transfer. In the triplet-triplet bimolecular process, the rates along the two different optical axes in the a-b crystalline plane differ by a factor of 4. This anisotropy in the triplet-triplet recombination rates was attributed to the interference in the coupling probability of dipole-dipole interactions in the different geometric configurations of hexacene single crystals. Our experimental findings provide new insight into future design of singlet fission materials with desirable triplet exciton exploitations.

5.
J Cell Mol Med ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925905

RESUMO

Chronic hepatitis B (CHB) is a global epidemic disease that may progress to fibrosis, cirrhosis and hepatocellular carcinoma. The role of the liver-bile acid-microbiota axis in CHB remains unclear. The aims of this study are to elucidate the alteration of the gut microbiota and its functions in bile acid homeostasis in CHB patients with different degrees of fibrosis. In the present study, we evaluated serum and faecal bile acid profiles in healthy controls and CHB patients with biopsy-proven diagnosis: patients had stage 0-1 fibrosis were classified as mild CHB and patients had stage 2-4 fibrosis were classified as moderate/advanced CHB. The levels of serum total bile acids (BAs) and primary BAs were increased in CHB patients with moderate/advanced fibrosis, whereas faecal total and secondary BAs levels were significantly lower. Analyses of gut microbiota exhibited a trend of decreased abundance in bacteria genera responsible for BA metabolism in CHB patients with moderate/advanced fibrosis. CHB is associated with altered bile acid pool which is linked with the dysregulated gut microbiota. The higher level of FGF-19 may act in a negative feedback loop for maintaining the bile acid homeostasis.

6.
J Asian Nat Prod Res ; : 1-6, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31979983

RESUMO

Two new compounds named asperpenes D (1) and E (2) were isolated from the marine-derived fungus Aspergillus sp. SCS-KFD66. Their structures were determined on the basis of spectroscopic methods. Compound 2 represents the first natural product bearing a 2-substituted-5-oxo-4-phenyl-2,5-dihydrofuran-3-carboxylic acid skeleton. All the compounds were tested for enzyme inhibitory activity against AChE and α-glucosidase and DPPH radical scavenging activity, respectively.

7.
Aliment Pharmacol Ther ; 51(4): 469-478, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31943297

RESUMO

BACKGROUND: To date, 14 single-nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB). AIM: To investigate if these SNPs are associated with treatment response of hepatitis B e antigen (HBeAg)-positive CHB patients. METHODS: We performed a retrospective analysis of 1623 Han Chinese HBeAg-positive CHB patients (782 patients treated with pegylated interferon alpha [PegIFNα] for 48 weeks plus 24 weeks follow-up, and 841 patients treated with nucleos(t)ide analogues [NUCs] for 104 weeks) included in four phase-IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed. RESULTS: We found that rs12614, a missense variant of complement factor B (CFB), was significantly associated with CR in PegIFNα-treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one-third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFNα) was significantly associated with both CR (P-trend = 4.000 × 10-4 ) and HBsAg loss (P-trend = 0.010) in PegIFNα-treated patients. However, none of the SNPs were associated with treatment response in NUCs-treated patients. CONCLUSIONS: CFB rs12614 is an independent predictor of response to PegIFNα therapy in Chinese HBeAg-positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFNα from nonresponders.

8.
Sci Total Environ ; 712: 136450, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31931195

RESUMO

Singlet oxygen (1O2) is capable of degrading organic contaminants and inducing cell damage and inactivation of viruses. It is mainly generated through the interaction of dissolved oxygen with excited triplet states of dissolved organic matter (DOM) in natural waters. The present study aims at revealing the underlying mechanism of 1O2 generation and providing a potential tool for predicting the quantum yield of 1O2 (Φ1O2) generation from DOM by constructing a quantitative structure-activity relationship (QSAR) model. The determined Φ1O2 values for the selected DOM-analogs range from (0.54 ± 0.23) × 10-2 to (62.03 ± 2.97) × 10-2. A QSAR model was constructed and was proved to have satisfactory goodness-of-fit and robustness. The QSAR model was successfully used to predict the Φ1O2 of Suwannee River fulvic acid. Mechanistic interpretation of the descriptors in the model showed that hydrophobicity, molecular complexity and the presence of carbonyl groups in DOM play crucial roles in the generation of 1O2 from DOM. The presence of other heteroatoms besides O, such as N and S, also affects the generation of 1O2. The results of this study provide valuable insights into the generation of 1O2 from DOM in sunlit natural waters.

9.
Chem Biodivers ; 17(1): e1900560, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31769919

RESUMO

Borrelidins M-O (1-3), along with four previously known family members (4-7), were isolated from marine pulmonated mollusks Onchidium sp. associated Streptomyces olivaceus SCSIO LO13. The structures of 1-3 were elucidated by extensive spectral analyses of HR-ESI-MS, 1D and 2D NMR data. In addition, the cytotoxic and antibacterial activities of 1-7 were evaluated enabling us to propose some tentative structure-activity relationships (SARs), especially those involving modifications at C(22) and the moieties at C(7) and C(8) of the borrelidin scaffold.

10.
J Infect Dis ; 221(3): 389-399, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31550363

RESUMO

BACKGROUND: Patients on oral antiviral (OAV) therapy remain at hepatocellular carcinoma (HCC) risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. The aim of this study was to develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort. METHODS: Adult Asian chronic hepatitis B (CHB) patients on OAV were recruited from 25 centers in the United States and the Asia-Pacific region. Excluded persons were coinfected with hepatitis C, D, or human immunodeficiency virus, had HCC before or within 1 year of study entry, or their follow-up was <1 year. Patients were randomized to derivation and validation cohorts on a 2:1 ratio. Statistically significant predictors from multivariate modeling formed the Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV (REAL-B) score. RESULTS: A total of 8048 patients were randomized to the derivation (n = 5365) or validation group (n = 2683). The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and alpha fetoprotein), and scores were categorized as follows: 0-3 low risk, 4-7 moderate risk, and 8-13 high risk. Area under receiver operating characteristics were >0.80 for HCC risk at 3, 5, and 10 years, and these were significantly higher than other risk models (p < .001). CONCLUSIONS: The REAL-B score provides 3 distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy.

11.
Clin Gastroenterol Hepatol ; 18(1): 196-204.e8, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31042581

RESUMO

BACKGROUND & AIMS: Variants in STAT4 (rs7574865) have been associated with seroconversion to hepatitis B e antigen (HBeAg) and reduction in levels of hepatitis B virus (HBV) DNA in patients with chronic infection treated with interferon alpha (IFNA). We evaluated the associations among rs7574865, loss of HB surface antigen (HBsAg, a marker of functional cure of HBV infection), and response to treatment with pegylated IFNA (PegIFN) or nucleos(t)ide analogues (NUCs) in HBeAg-positive patients with chronic HBV infection. METHODS: We performed a retrospective analysis of 1823 HBeAg-positive patients with chronic HBV infection (954 patients treated with PegIFN and 869 patients treated with NUCs) included in 4 phase-4 multicenter randomized controlled trials. The Cochran-Armitage trend test was used to evaluate the association of rs7574865 genotype with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <2000 IU/mL) and loss of HBsAg at week 72, for patients given PegIFN, or week 104, for patients given NUCs. RESULTS: We found a significant association between rs7574865 genotype and CR (P = .004) and loss of HBsAg (P = .037) in patients treated with PegIFN. In patients with HBV genotype B infection, 43.6% of those with rs7574865 TT achieved a CR, compared to patients with rs7574865 GG (20.5%), and 7.7% had loss of HBsAg, compared to 1.9% of patients with rs7574865 GG. However, in patients treated with NUCs, we found no association of rs7574865 genotype with CR (P = .811) or loss of HBsAg (P=.439). CONCLUSIONS: In a retrospective analysis of data from 4 clinical trials, we found rs7574865 in STAT4 to be associated with functional cure of chronic HBV infection by PegIFN treatment, but not NUCs treatment, in HBeAg-positive patients with HBV genotype B infection.

12.
Clin Gastroenterol Hepatol ; 18(2): 457-467.e21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31306800

RESUMO

BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.

13.
J Hazard Mater ; 381: 120962, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31442691

RESUMO

Water-level-fluctuating zone (WLFZ) is a prevalent water-land ecotone favorable for mercury (Hg) methylation. The succession of flooding tolerance plants in WLFZ gradually changes the landscape, and also brings a new question worth understanding whether these plants would enhance methylmercury (MeHg) production in WLFZ and increase risks to the aquatic environment. Given bermudagrass (Cynodon dactylon (L). Pers) as the dominant perennial herb with high flooding-tolerance in WLFZ of the Three Gorges Reservoir (TGR), we conducted a comprehensive study to investigate its roles in the production and migration of MeHg in WLFZ by field observations and stable isotope tracer experiments. Results showed that both elevated MeHg levels and Hg methylation rates appeared in soil/sediment in bermudagrass growing area, implying that the growth of bermudagrass could significantly enhance MeHg production. However, MeHg migration from sediment to water was restricted during the flooding period of the TGR, as obviously higher partitioning coefficients of MeHg between the sediment and porewater (p <  0.05) and lower MeHg release fluxes were observed in vegetated area, indicating that the presence of bermudagrass instead probably decreased the water MeHg level. Whereas, it is noteworthy that elevated MeHg in soil/sediment induced by the bermudagrass could pose potential risks to the benthos and further to the TGR food chain.

14.
J Hepatol ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31786256

RESUMO

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome defined by liver failure on pre-existing chronic liver disease. It is often associated with bacterial infection and high short-term mortality. Experimental models that fully reproduce ACLF are lacking, so too are effective pharmacological therapies for this condition. METHODS: To mimic ACLF conditions, we developed a severe liver injury model by combining chronic injury (chronic carbon tetrachloride [CCl4] injection), acute hepatic insult (injection of a double dose of CCl4), and bacterial infection (intraperitoneal injection of bacteria). Serum and liver samples from patients with ACLF or acute drug-induced liver injury (DILI) were used. Liver injury and regeneration were assessed to ascertain the potential benefits of interleukin-22 (IL-22Fc) administration. RESULTS: This severe liver injury model recapitulated some of the key features of clinical ACLF, including acute-on-chronic liver injury, bacterial infection, multi-organ injury, and high mortality. Liver regeneration in this model was severely impaired because of a shift from the activation of the pro-regenerative IL-6/STAT3 pathway to the anti-regenerative IFN-γ/STAT1 pathway. The impaired IL-6/STAT3 activation was due to the inability of Kupffer cells to produce IL-6; whereas the enhanced STAT1 activation was due to a strong innate immune response and subsequent production of IFN-γ. Compared to patients with DILI, patients with ACLF had higher levels of IFN-γ but lower liver regeneration. IL-22Fc treatment improved survival in ACLF mice by reversing the STAT1/STAT3 pathway imbalance and enhancing expression of many antibacterial genes in a manner involving the anti-apoptotic protein BCL2. CONCLUSIONS: Acute-on-chronic liver injury or bacterial infection is associated with impaired liver regeneration due to a shift from a pro-regenerative to an anti-regenerative pathway. IL-22Fc therapy reverses this shift and attenuates bacterial infection, thus IL-22Fc may have therapeutic potential for ACLF treatment. LAY SUMMARY: A mouse model combining chronic liver injury, acute hepatic insult, and bacterial infection recapitulates some of the key features of acute-on-chronic liver failure (ACLF) in patients. Both fibrosis and bacterial infection contribute to the impaired regenerative capacity of the liver in patients with ACLF. Herein, we show that IL-22Fc therapy improves ACLF by reprogramming impaired regenerative pathways and attenuating bacterial infection. Thus, it may have therapeutic potential for patients with ACLF.

15.
J Nat Prod ; 82(12): 3456-3463, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31823605

RESUMO

Seven new quinazoline-containing indole alkaloids (1-7) named aspertoryadins A-G, along with nine known ones (8-16), were isolated from the marine-derived fungus Aspergillus sp. HNMF114 from the bivalve mollusk Sanguinolaria chinensis. The structures of the new compounds were elucidated from spectroscopic data, X-ray diffraction analysis, ECD spectra analysis, and ECD calculations. Compound 1 bears an aminosulfonyl group in the structure, which is rarely encountered in natural products. Compounds 6, 7, and 13 exhibited quorum sensing inhibitory activity against Chromobacterium violaceum CV026 with MIC values of 32, 32, and 16 µg/well, respectively.

16.
Clin Chim Acta ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31794766

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease with high disability rate, and it is sometimes difficult to distinguish from generalized osteoarthritis (GOA). Deoxyribonuclease 1-like 3 (DNASE1L3) was associated with a variety of autoimmune diseases. However, the serum DNASE1L3 level in AS and GOA remain unreported. Herein, this study was designed to gauge serum DNASE1L3 level in patients with AS and GOA, and to discern the utility of serum DNASE1L3 as a biomarker for assessing the severity of patients with AS. METHODS: The study population consisted of 60 patients with AS, 60 patients with GOA and 60 control subjects. Serum DNASE1L3 levels were measured using enzyme-linked immunosorbent assay (ELISA) assay. Disease activity were assessed with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS patients. RESULTS: Our data showed that serum DNASE1L3 levels were significantly higher in patients with AS than that of the healthy controls and patients with GOA. Serum DNASE1L3 levels in patients with AS were positively correlated with BASDAI scores, C3 and C-reactive protein (CRP). Furthermore, serum DNASE1L3 showed higher discriminatory accuracy in the diagnosis of AS from GOA (AUC = 0.851, sensitivity = 78.33% and specificity = 81.67%). CONCLUSIONS: Elevated Serum DNASE1L3 levels in patients with AS were significantly associated with the clinic features and disease activity. DNASE1L3 could be a serum biomarker with a positive diagnostic value in patients with AS, and which could be used as a differential diagnostic indicator for GOA and AS.

17.
BMC Med Inform Decis Mak ; 19(Suppl 5): 240, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31801521

RESUMO

BACKGROUND: Extracting useful information from biomedical literature plays an important role in the development of modern medicine. In natural language processing, there have been rigorous attempts to find meaningful relationships between entities automatically by co-occurrence-based methods. It has been increasingly important to understand whether relationships exist, and if so how strong, between any two entities extracted from a large number of texts. One of the defining methods is to measure semantic similarity and relatedness between two entities. METHODS: We propose a hybrid ranking method that combines a co-occurrence approach considering both direct and indirect entity pair relationship with specialized word embeddings for measuring the relatedness of two entities. RESULTS: We evaluate the proposed ranking method comparatively with other well-known methods such as co-occurrence, Word2Vec, COALS (Correlated Occurrence Analog to Lexical Semantics), and random indexing by calculating top-ranked entities related to Alzheimer's disease. In addition, we analyze gene, pathway, and gene-phenotype relationships. Overall, the proposed method tends to find more hidden relationships than the other methods. CONCLUSION: Our proposed method is able to select more useful related entities that not only highly co-occur but also have more indirect relations for the target entity. In pathway analysis, our proposed method shows superior performance at identifying (functional) cross clustering and higher-level pathways. Our proposed method, resulting from phenotype analysis, has an advantage in identifying the common genotype relating to phenotypes from biological literature.

18.
Cancer Manag Res ; 11: 9185-9193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802943

RESUMO

Objective: This study aims to evaluate the potential role of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in detecting high-grade meningiomas and predicting the prognosis of patients after meningioma surgery. Patients and methods: A total of 124 patients met the final inclusion criterion. Tumor to gray ratio (TGR) was compared with Ki-67 labeling index, and its correlations with pre-operative neurological function and treatment status were also evaluated. Receiver-operating characteristic (ROC) curve was drawn to determine a cut-off value which could discriminate meningioma of different grades. Prognostic factors including TGR were analyzed using Kaplan-Meier survival curve and cox proportional model. Results: The TGR of higher World Health Organization (WHO) grade meningioma was significantly higher than that in lower grade (p < 0.001), and it was correlated with the Ki-67 labeling index (p < 0.001, r = 0.1545). The TGR of 1.30 was the best cutoff value for the detection of high grade (WHO grade II&III) meningioma from low grade (WHO grade I) according to ROC analysis, with a sensitivity of 61.5%, the specificity of 86.7%, and accuracy of 81.5%. The TGR (p < 0.001), treatment status (p = 0.035), tumor grade (p < 0.001) and Ki-67 labeling index (p < 0.001) were significantly associated with progression-free survival (PFS). Cox proportional hazards model demonstrated that TGR (p = 0.013) was an independent prognostic factor for PFS. Conclusion: A high uptake of FDG was correlated with a more proliferative biological behavior and is a risk factor for tumor recurrence.

19.
Environ Pollut ; 258: 113700, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31838398

RESUMO

Dissolved organic matter (DOM) is the most important light absorber that may induce indirect photolytic transformation of organic pollutants in natural waters. In this study, effects of DOM derived from freshwater and seawater on the photodegradation of three antiviral drugs acyclovir, lamivudine and zidovudine were investigated. Results show that the photodegradation of acyclovir is promoted mainly by excited triplet states DOM (3DOM*), and the photodegradation of lamivudine is accelerated by 3DOM*, •OH and 1O2 together; however, the photodegradation of zidovudine is inhibited by DOM mainly via light screening. Compared with DOM from freshwater, promotion effect of DOM extracted from seawater (SDOM) on the photodegradation of acyclovir and lamivudine is weaker, which is attributed to lower productivity of reactive intermediates. On the other hand, inhibitory effect of SDOM on the photodegradation of zidovudine is also weaker, which is due to weaker light screening caused by lower light absorption. Photodegradation half-lives of the three antiviral drugs are predicted to be all more than 20 days in freshwater and seawater bodies of the Yellow River estuarine region. These findings are significant for understanding the phototransformation processes of antiviral drugs and other organic pollutants in estuarine and coastal regions.

20.
Commun Biol ; 2: 454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31840099

RESUMO

Antibiotic-producing microorganism can develop strategies to deal with self-toxicity. Cytorhodins X and Y, cosmomycins A and B, and iremycin, are produced as final products from a marine-derived Streptomyces sp. SCSIO 1666. These C-7 reduced metabolites show reduced antimicrobial and comparable cytotoxic activities relative to their C-7 glycosylated counterparts. However, the biosynthetic mechanisms and relevant enzymes that drive C-7 reduction in cytorhodin biosynthesis have not yet been characterized. Here we report the discovery and characterization of a reductase, CytA, that mediates C-7 reduction of this anthracycline scaffold; CytA endows the producer Streptomyces sp. SCSIO 1666 with a means of protecting itself from the effects of its anthracycline products. Additionally, we identified cosmomycins C and D as two intermediates involved in cytorhodin biosynthesis and we also broadened the substrate specificity of CytA to clinically used anthracycline drugs.

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