Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.201
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Sci Rep ; 10(1): 102, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919462

RESUMO

Basidioradulum was morphologically considered to be a synonym of Xylodon. Here, its independence within Hymenochaetales is confirmed from a phylogenetic perspective. Basidioradulum radula, the generic type, is widely distributed in Northern Hemisphere. Two Southern Hemisphere species close to B. radula are newly described as B. mayi and B. tasmanicum, respectively, from Victoria and Tasmania, Australia. Basidioradulum mayi differs from B. radula by lack of cystidia. Moreover, the hymenial surface of B. radula is normally much more strongly hydnoid than that of B. mayi. Basidioradulum tasmanicum is distinct from B. radula and B. mayi by having capitate cystidia, ellipsoid to subglobose basidiospores, and crystal-covered hyphae. Although morphologically distinct, the two new species isolated by Bass Strait have an almost identical ITS region, and could not be differentiated by nLSU- and ITS-based phylogenetic analyses. This case reminds us that basing phylogeny simply on the ITS as a barcode region may underestimate fungal species diversity.

2.
Mol Pharm ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913047

RESUMO

Plant-based saponins are amphipathic glycosides composed of a hydrophobic aglycone backbone covalently bound to one or more hydrophilic sugar moieties. Recently, the endosomal escape activity of triterpenoid saponins has been investigated as a potentially powerful tool for improved cytosolic penetration of protein drugs internalized by endocytic uptake, thereby greatly enhancing their pharmacological effects. However, only a few saponins have been studied, and the paucity in understanding the structure-activity relationship of saponins imposes significant limitations on their applications. To address this knowledge gap, 12 triterpenoid saponins with diverse structural side chains were screened for their utility as endosomolytic agents. These compounds were used in combination with a toxin (MAP30-HBP) comprising a type I ribosome-inactivating protein fused to a cell-penetrating peptide. Suitability of saponins as endosomolytic agents were assessed on the basis of cytotoxicity, endosomal escape promotion and synergistic effects on toxins. Five saponins showed strong endosomal escape activity, enhancing MAP30-HBP cytotoxicity by more than 10^6 - 10^9 folds. These saponins also enhanced the apoptotic effect of MAP30-HBP in a pH-dependent manner. Additionally, growth inhibition of MAP30-HBP treated SMMC-7721 cells was greater than that of similarly treated HeLa cells, suggesting that saponin-mediated endosomolytic effect is likely to be cell-specific. Furthermore, the structural features and hydrophobicity of the sugar side chains were analyzed to draw correlations with endosomal escape activity and derive predictive rules, thus providing new insights into structure-activity relationships of saponins. This study revealed new saponins that can potentially be exploited as efficient cytosolic delivery reagents for improved therapeutic drug effects.

3.
J Dairy Sci ; 103(1): 220-227, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704015

RESUMO

This study was conducted to analyze the effect of milk types on the attributes of the glutinous rice wine-fermented yogurt-like product named Kouwan Lao (KWL). Four types of raw milks were used in this study, including high temperature, long time (HTLT: H milk), HTLT milk supplemented with 3% skim milk powder (S milk), pasteurized milk (P milk), and ultra-high temperature milk (U milk). Microbiological compositions of the fermented glutinous rice and KWL at different stages were analyzed using PCR-denaturing gradient gel electrophoresis and gene sequencing based on 16S rRNA and 26S rRNA. The physicochemical properties of KWL samples were determined, and textural properties of those were analyzed using a texture analyzer (Jiawei Innovation and Technology Co. Ltd., Zhejiang Province, China). The microstructure of KWL samples was observed using scanning electron microscopy. The results showed that the milk types had significant influences on the bacterial composition of KWL. In the curdling process, the predominant bacteria of H, S, P, and U KWL samples were Lactobacillus brevis, Janthinobacterium sp., Lactobacillus casei, and Streptococcus agalactiae, respectively. In the ripening process, the main strains in H KWL were Enterococcus faecium and Pediococcus pentosaceus. Lactobacillus casei and Lactobacillus paracasei were the dominant bacteria of U KWL. Lactobacillus casei was the main strain of P KWL, and no bacteria were detected in S KWL. Saccharomyces cerevisiae was the dominant fungus of KWL, and no significant effect of milk types on fungal composition of KWL was found. The results of physicochemical properties showed that significant differences in protein contents were found in the KWL samples, and P KWL had the highest protein content. The fat content of U KWL was significantly higher than that of samples from the other 3 groups. The U KWL and P KWL showed lower moisture than that of the other 2 KWL samples. In addition, no significant difference in pH value was found in all samples. The results of texture analysis and microstructure showed that compared with other 3 types of KWL samples, the related mass parameters of U KWL were more advantageous and improved significantly with the increase of the heat treatment temperature of raw milk and the addition of skim milk powder. Our findings revealed the effects of milk types on microbial composition, physicochemical properties, textural properties, and microstructure of KWL, and provided a basic theory for the optimization and industrial production of KWL.

4.
Am J Mens Health ; 13(6): 1557988319894480, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31838943

RESUMO

Holmium laser enucleation of the prostate (HoLEP) is one of the minimally invasive procedures that is used for patients with benign prostate hyperplasia. The procedure usually requires patients to stay in the hospital 2 nights or longer. The present study evaluated the safety and feasibility of HoLEP with discharge of the patients on Day 1 after surgery (1-day surgery). A total of 1,164 patients were included in the study, with 510 of them planned for 1-day surgery and others planned for inpatient surgery. The primary outcomes included complication rate and clinical outcomes. A total 489 out of 510 patients received 1-day HoLEP and were discharged on Day 1 after surgery. In a 30-day follow-up period, no significant differences were found between the 1-day and inpatient surgery groups in terms of the rate of complications and clinical outcomes. Patients in the 1-day surgery group had a significantly shorter waiting time for admission (9.5 ± 4.8 vs. 17.6 ± 7.4 days, p < .05), and the mean hospitalization cost was lower (CNY$ 9140.6 ± 1452.2 vs. 10533.4 ± 1594, p < .05).The 1-day HoLEP surgery was safe and had satisfactory clinical outcomes. This treatment strategy could reduce the waiting time for admission and cost of hospitalization. Majority of the patients found this 1-day surgery beneficial, especially elderly patients who prefer to have an early return home and rapid resumption of activities.

5.
Chem Commun (Camb) ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31825446

RESUMO

In this study, a multi-step phase transition hybrid composed of (Pr-dabco)2Ag4I6 clusters (Pr-dabco+ = 1-propyl-1,4-diazabicyclo[2.2.2]octan-1-ium) has been prepared and characterized by microanalysis, IR and UV-vis spectroscopy, TG and DSC techniques, etc. This hybrid is thermally stable up to ∼486 K with five phases in the temperature region below 486 K. The phase transition shows symmetry breaking (SB) character between phases II (space group P21/c) and III (space group Pa3[combining macron]), while inverse symmetry breaking (ISB) between phases II and I (space group Pbca), and it is rather exceptional for matter to exhibit simultaneously SB and ISB nature in two successive phase transitions. Most importantly, each phase transition is associated with a dielectric anomaly, and phase V appears to be a plastic crystal with extra high ac conductivity (>10-2 S cm-1). Our work opens up new avenues to find a multi-phase transition material in silver halide hybrids.

6.
Sci Rep ; 9(1): 20034, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882989

RESUMO

Resistance of cancer cells to chemotherapy is a significant clinical concern and mechanisms regulating cell death in cancer therapy, including apoptosis, autophagy or necrosis, have been extensively investigated over the last decade. Accordingly, the identification of medicinal compounds against chemoresistant cancer cells via new mechanism of action is highly desired. Autophagy is important in inducing cell death or survival in cancer therapy. Recently, novel autophagy activators isolated from natural products were shown to induce autophagic cell death in apoptosis-resistant cancer cells in a calcium-dependent manner. Therefore, enhancement of autophagy may serve as additional therapeutic strategy against these resistant cancers. By computational docking analysis, biochemical assays, and advanced live-cell imaging, we identified that neferine, a natural alkaloid from Nelumbo nucifera, induces autophagy by activating the ryanodine receptor and calcium release. With well-known apoptotic agents, such as staurosporine, taxol, doxorubicin, cisplatin and etoposide, utilized as controls, neferine was shown to induce autophagic cell death in a panel of cancer cells, including apoptosis-defective and -resistant cancer cells or isogenic cancer cells, via calcium mobilization through the activation of ryanodine receptor and Ulk-1-PERK and AMPK-mTOR signaling cascades. Taken together, this study provides insights into the cytotoxic mechanism of neferine-induced autophagy through ryanodine receptor activation in resistant cancers.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31878125

RESUMO

High air pollution levels have become a nationwide problem in China, but limited attention has been paid to prefecture-level cities. Furthermore, different time resolutions between air pollutant level data and meteorological parameters used in many previous studies can lead to biased results. Supported by synchronous measurements of air pollutants and meteorological parameters, including PM2.5, PM10, total suspended particles (TSP), CO, NO2, O3, SO2, temperature, relative humidity, wind speed and direction, at 16 urban sites in Xiangyang, China, from 1 March 2018 to 28 February 2019, this paper: (1) analyzes the overall air quality using an air quality index (AQI); (2) captures spatial dynamics of air pollutants with pollution point source data; (3) characterizes pollution variations at seasonal, day-of-week and diurnal timescales; (4) detects weekend effects and holiday (Chinese New Year and National Day holidays) effects from a statistical point of view; (5) establishes relationships between air pollutants and meteorological parameters. The principal results are as follows: (1) PM2.5 and PM10 act as primary pollutants all year round and O3 loses its primary pollutant position after November; (2) automobile manufacture contributes to more particulate pollutants while chemical plants produce more gaseous pollutants. TSP concentration is related to on-going construction and road sprinkler operations help alleviate it; (3) an unclear weekend effect for all air pollutants is confirmed; (4) celebration activities for the Chinese New Year bring distinctly increased concentrations of SO2 and thereby enhance secondary particulate pollutants; (5) relative humidity and wind speed, respectively, have strong negative correlations with coarse particles and fine particles. Temperature positively correlates with O3.

8.
Yi Chuan ; 41(12): 1110-1118, 2019 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-31857282

RESUMO

Myogenesis is a complex physiological process that is mainly involved in the proliferation of myogenic stem cells to form myoblasts, which then differentiated and fused to form multinucleated myotubes. Many proteins have been found to be involved in myoblast fusion, but none of them are muscle-specific fusion proteins. In recent years, two muscle-specific transmembrane proteins, i.e. Myomaker and Myomerger, have been discovered and identified, which can coordinate and promote the fusion of myoblasts and thus participate in the process of myogenesis. In this review, we summarize the research progress of Myomaker and Myomerger in myogenesis, including their expression patterns and functional domains, as well as their participation in myoblast fusion mechanisms, aiming to provide relevant ideas for in-depth study of the myogenesis process and treatment of diseases related to myoblast fusion.


Assuntos
Proteínas de Membrana , Músculo Esquelético , Mioblastos , Animais , Diferenciação Celular , Fusão Celular , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Desenvolvimento Muscular , Proteínas Musculares , Músculo Esquelético/citologia , Mioblastos/citologia
9.
Lasers Med Sci ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31858348

RESUMO

To explore the surgical effect and cost-effectiveness of day surgery versus inpatient surgery for photoselective vaporization of the prostate (PVP) in Chinese population. We retrospectively collected 240 patients undergoing day-surgery PVP (April 2016 to March 2018) and 156 patients undergoing inpatient-surgery PVP (May 2014 to March 2016). Differences between groups in demographics, perioperative outcomes, complications, and postoperative changes were calculated. Economical results in terms of hospital stay and relevant preoperative, intraoperative, and postoperative cost were evaluated. There was no significant difference in operative time, incidence of postoperative complications, and other functional outcomes between two groups (P > 0.05), but the waiting time for admission and the hospital cost including the drug charges, bed fee, nursing fee, laboratory test, and imaging fee of day-surgery group were significantly lower than that of inpatient-surgery group (P < 0.05). Day surgery of PVP has firm and well accepted position in ambulatory surgery of urology. It could significantly reduce the waiting time for admission and hospitalization costs in BPH patients.

10.
Huan Jing Ke Xue ; 40(11): 4810-4823, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854546

RESUMO

Northeastern China experiences severe atmospheric pollution, with an increasing occurrence of heavy haze episodes. Based on ground monitoring data, satellite products and meteorological products of atmospheric pollutants in northeast China from 2013 to 2017, the characteristics of spatial and temporal distribution of air quality and the causes of heavy haze events in northeast China were discussed. It was found that the "Shenyang-Changchun-Harbin" city belt was the most polluted area in the region on an annual scale. The spatial distribution of air quality index (AQI) values had a clear seasonality, with the worst pollution occurring in winter, an approximately oval-shaped polluted area around western Jilin Province in spring, and the best air quality occurring in summer and most of autumn. The three periods that typically experienced intense haze events were Period I from late-October to early-November (i. e., late autumn and early winter), Period Ⅱ from late-December to January (i. e., the coldest time in winter), and Period Ⅲ from April to mid-May (i. e., spring). During Period I, strong PM2.5 emissions from seasonal crop residue burning and coal burning for winter heating were the dominant reasons for the occurrence of extreme haze events (AQI>300). Period Ⅱ had frequent heavy haze events (200 < AQI < 300) in the coldest months of January and February(200 < AQI < 300), which were due to high PM2.5 emissions from coal burning and vehicle fuel consumption, a lower atmospheric boundary layer, and stagnant atmospheric conditions. Haze events in Period Ⅲ, with high PM10 concentrations, were primarily caused by the regional transportation of windblown dust from degraded grassland in central Inner Mongolia and bare soil in western Jilin Province. Local agricultural tilling could also release PM10 and enhance the levels of windblown dust from tilled soil.

11.
Nanomaterials (Basel) ; 9(11)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671586

RESUMO

It is essential to develop a novel and versatile strategy for constructing electrically conductive adhesives (ECAs) that have superior conductivity and high mechanical properties. In this work, easily synthesized polyaniline@cellulose (PANI@CNs) nanowhiskers with a high aspect ratio and excellent solubility in 1,4-dioxane were prepared and added to conventional Ag-containing adhesives. A small amount of PANI@CNs can dramatically tune the structure of the ECAs' conductive network and significantly improve the conductivity of the ECAs. Good solubility of PANI@CNs in solvents brings excellent dispersion in the polymer matrix. Thus, a three-dimensional (3D) conducting network formed with dispersed PANI@CNs and Ag flakes can enhance the conductivity of ECAs. The conductivity of the ECAs (with 1.5 wt% PANI@CNs and 55 wt% Ag flakes) showed three orders of magnitude higher than that of the ECAs filled with 55 wt% Ag flakes and 65 wt% Ag flakes. Meanwhile, the integration of PANI@CNs with Ag flakes in polymer matrices also significantly enhanced the mechanical compliance of the resulted ECAs. The resistivity remained unchanged after rolling the PANI@CNs-containing ECAs' film into a 4 mm bending radius for over 1500 cycles. A bendable printed circuit was fabricated using the above PANI@CNs-containing ECAs, which demonstrated their future potential in the field of flexible electronics.

12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 714-719, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762243

RESUMO

OBJECTIVE: To select and identify the bacterium which highly produces protease and ß-D-glucosidase from 72 strains of Shuidouchi from Sichuan, and to provide evidence for further research on its nutritional value and fermentation strain exploiting. METHODS: Casein degradation test and pNPG chemical test were applied respectively to detect the capacity to produce protease and ß-D-glucosidase of each strain. Characteristics of morphology, biochemistry, 16S rRNA and MALDI-TOF-MS were used to identify the fermentation strain, which genetic stability, curves of growth and enzyme producing were also obtained. RESULTS: The strain with the highest enzyme activity of ß-D-glucosidase (0.084 U/L) among the top 10 strains for producing protease was selected as the fermentation strain and was identified as Bacillus subtilis, which curves of growth and enzyme producing conformed as well. The result of genetic stability showed that capacity of enzyme producing was stable until the 10th generation. CONCLUSIONS: The fermentation strain which highly produced protease and ß-D-glucosidase was selected from 72 strains of shuidouchi from Sichuan and was identified as Bacillus subtilis.


Assuntos
Bacillus subtilis/enzimologia , Glucosidases/biossíntese , Peptídeo Hidrolases/biossíntese , Alimentos de Soja/microbiologia , China , Fermentação , RNA Ribossômico 16S
13.
J Agric Food Chem ; 67(47): 13033-13039, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31730339

RESUMO

Three new macrocyclic trichothecenes possessing rare 6'-ketal moieties, roridoxins A-C (1-3), and five known compounds (4-8) were isolated from the insect-associated fungus Myrothecium roridum. Their structures were confirmed by a combination of NMR and HRESIMS data, while their absolute configurations were unambiguously determined by single-crystal X-ray analysis and electronic circular dichroism experiments. Trichothecenes 1 and 3 showed potent antifungal activities against four strains of phytopathogenic fungi. In addition, 1, 3, 5, and 6 were found to significantly inhibit the cell growth of Candida albicans with minimal inhibitory concentration values from 8.8 to 18.5 µg/mL. Moreover, they were able to inhibit the biofilm formation of C. albicans better than the positive control.

14.
Int J Biol Macromol ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756484

RESUMO

In this study, an endophytic actinobacterium Glutamicibacter halophytocola KLBMP 5180, was investigated for the production and antioxidant activity of exopolysaccharides (EPSs). First, the suitable fermentation time, temperature, inoculation volume, pH value, and the carbon and nitrogen sources for EPSs production were obtained using the one variable at a time method (OVAT). Then, a central composition design was used for fermentation conditions optimization to obtain the maximum EPS yield. The optimal medium and condition were as follows: 100 mL broth in 250 mL Erlenmeyer flasks, including 3.65 g/L maltose, 9.88 g/L malt extract, 3.40 g/L yeast extract, 1.41 g/L MnCl2, pH 7.5, culture temperature 28 °C, and 200 rpm for 7 days, which increased the yield of EPSs to 2.89 g/L. Two purified EPSs, 5180EPS-1 (MW 58.9 kDa) and 5180EPS-2 (10.5 kDa), comprising rhamnose, galacturonic acid, glucose, glucuronic acid, xylose, and arabinose, were obtained for chemical analysis and antioxidant evaluation. The scavenging ability and reducing power of the superoxide anion and hydroxyl radicals demonstrated the moderate in vitro antioxidant activities of the two EPSs, thus indicating their potential to be a new source of natural antioxidants. However, further structure elucidation and functional studies need to be continued.

15.
Clin Chim Acta ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31758937

RESUMO

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in men, but its metabolic characteristics during tumor progression are still far from being fully understood. METHODS: The metabolic profiles of matched tissue, serum and urine samples from the same patients were analyzed using a 1H NMR-based metabolomics approach. We identified several important metabolites that significantly altered at different stages of PCa, including benign prostatic hyperplasia (BPH), early PCa (EPC), advanced PCa (APC), metastatic PCa (MPC) and castration-resistant PCa (CRPC). Metabolic correlation networks among tissue, serum and urine samples were examined using Pearson's correlation. RESULTS: The changes in metabolic phenotypes during the progression of PCa were more noticeable in tissue samples when compared with serum and urine samples. Herein we identified a series of important metabolic disturbances, including decreased trends of citrate, creatinine, acetate, leucine, valine, glycine, lysine, histidine, glutamine and choline as well as increased trends of uridine and formate. These metabolites are mainly implicated in energy metabolism, amino acid metabolism, choline and fatty acid metabolism as well as uridine metabolism. We also found that energy metabolism in tumor tissues was positively associated with amino acid metabolism in serum and urine. Additionally, CRPC patients had a peculiar metabolic phenotype, especially decreased amino acid metabolism in serum. CONCLUSIONS: The present study characterizes metabolic disturbances in both tissue and biofluid samples during PCa progression and provides potential diagnostic biomarkers and therapeutic targets for PCa.

16.
Math Biosci Eng ; 16(6): 6892-6906, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31698594

RESUMO

Alzheimer's disease (AD) is a neurological degenerative disease, which is mainly char-acterized by the memory loss. As electroencephalogram (EEG) device is relatively cheap, portable and non-invasive, it has been widely used in AD-related studies. We proposed a method to detect the differences between healthy subjects and AD patients, which combines classical sample entropy (Sam-pEn) and surrogate data method. EEGs from 14 AD patients and 20 healthy subjects were analyzed. The results based on the original data showed that the SampEn of AD patients was significantly de-creased (p < 0.01) at electrodes c3, f3, o2 and p4, which confirmed that AD could cause complexity loss. However, using original data could be subject to human judgement, so we generated a series of surrogate data. We found that, there were significant difference of SampEn between the original time series and their surrogate data at c3 and o2 electrodes and the differences between healthy subjects and AD patients can be verified. Our method is capable of distinguishing AD patients from healthy subjects, which is consistent with the concept of physiologic complexity, and providing insights for understanding of AD.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31745702

RESUMO

OBJECTIVE: To assess the use of the cell cycle progression (CCP) score versus actual risk stratification practice in making treatment decisions for prostate cancer patients with locally adverse pathology after radical prostatectomy (RP). PATIENTS AND METHODS: Men with adverse pathologic features, pT3 or positive surgical margins who underwent RP in 2010-2014 at Renji hospital were retrospectively analyzed. The primary outcome was biochemical recurrence (BCR) after RP. RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. The prognostic utility of the CCP score was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards model. RESULTS: Among the 100 men identified, 5-year BCR-free survival for the low- (< 0), intermediate- (0-1) and high- (> 1) CCP score groups was 89.3%, 38.8%, and 12.9%, respectively. In multivariable models adjusting for clinical and pathological variables with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score, both continuous CCP score [hazard ratio (HR) 1.373 per unit score, 95% confidence interval (CI) 1.006-1.874; p = 0.046) and the categorized CCP score (p < 0.001)were independent predictors of BCR. CONCLUSIONS: The present study provides insights into the role the CCP score plays in risk stratification of this cohort and in determining candidacy for deferred secondary treatment. From our perspective, the CCP score allows better stratification and can help identifying patients at lower risk of disease recurrence who could benefit from a wait-and-see policy.

18.
Hemoglobin ; 43(4-5): 289-291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31690135

RESUMO

A female of Chinese origin carried the codon 43 (G>T) (HBB: c.130G > T) and codons 71/72 (+A) (HBB: c.216_217insA) mutations of the ß-globin gene in cis, identified during prenatal thalassemia screening. The double in cis mutations were inherited from her mother. Both of the two carriers behave as a traditional heterozygote for ß-thalassemia (ß-thal) with microcytosis and a high Hb A2 level. This case report indicates that the possibility of multiple mutations in cis in a fetus with thalassemia trait has to be considered in a prenatal screening program.

19.
Int J Clin Oncol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31720994

RESUMO

OBJECTIVE: PBRM1, located on 3p21, functions as a tumor suppressor and somatic mutation of PBRM1 is frequent in clear cell renal cell carcinoma (ccRCC). This study aims to determine the influence of PBRM1 expression on the prognosis of patients with mRCC receiving tyrosine kinase inhibitor (TKI) treatment. METHODS: We identified 116 mRCC patients who were administered sunitinib or sorafenib as first-line therapy, between January 2006 and December 2016 at our institution. PBRM1 expression was assessed by immunohistochemistry. The Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS), log-rank test was used to compare the survival outcomes between patients with low and high PBRM1 expression levels, and the Cox proportional hazard regression model was used to estimate the prognostic value. Prognostic accuracy was determined using Harrell concordance index, and nomograms were built to evaluate the prognosis of mRCC. RESULTS: Patients with low PBRM1 expression had significantly shorter median PFS (9 vs 26 months, P < 0.001) and OS (21 vs 44 months, P < 0.001) than those with high expression. Multivariate analysis showed that PBRM1 expression was an independent predictor of PFS (HR 1.975, P = 0.013) and OS (HR 2.282, P = 0.007). The model built by the addition of PBRM1 improved the C-index of PFS and OS to 0.72 and 0.82, respectively. CONCLUSIONS: The expression of PBRM1 could be a significant prognostic factor for mRCC patients treated with targeted therapy, and it increases the prognostic accuracy of the established prognostic model.

20.
FEBS Lett ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721178

RESUMO

The constituent paired helical filaments (PHFs) in neurofibrillary tangles are insoluble intracellular deposits central to the development of Alzheimer's disease (AD) and other tauopathies. Full-length tau requires the addition of anionic cofactors such as heparin to enhance assembly. We have shown that a fragment from the proteolytically stable core of the PHF, tau 297-391 known as 'dGAE', spontaneously forms cross-ß-containing PHFs and straight filaments under physiological conditions. Here, we have analysed and compared the structures of the filaments formed by dGAE in vitro with those deposited in the brains of individuals diagnosed with AD. We show that dGAE forms PHFs that share a macromolecular structure similar to those found in brain tissue. Thus, dGAEs may serve as a model system for studying core domain assembly and for screening for inhibitors of tau aggregation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA