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Background Retrospective or single-center prospective studies with relatively small samples have shown that contrast-enhanced US (CEUS) can improve the diagnostic accuracy of percutaneous biopsy, but larger prospective studies are lacking. Purpose To assess the diagnostic performance of CEUS-guided biopsy (CEUS-GB) of focal liver lesions (FLLs) compared with US-guided biopsy (US-GB) in a prospective multicenter study. Materials and Methods In this randomized controlled study conducted in nine hospitals in China between March 2016 and August 2019, adult participants with FLLs detected with US, CT, or MRI and planned for percutaneous biopsy were randomly assigned to undergo either US-GB or CEUS-GB. Lesions diagnosed as malignant at histopathologic analysis were considered true-positive findings. Benign or indeterminate lesions required further confirmation with either repeat biopsy or clinical follow-up at 6 months or later. The primary endpoint was the diagnostic accuracy rate, and comparison between groups was made using the χ2 test. Results In this study, 2056 participants (1297 men, 759 women; mean age, 58 years ± 11 [SD]) were analyzed: 1030 underwent biopsy with US guidance and 1026 underwent biopsy with CEUS guidance. The overall diagnostic accuracy rate of CEUS-GB was 96% (983 of 1026) versus 93% (953 of 1030) for US-GB (P = .002), CEUS-GB enabled correct identification in 96% of participants (983 of 1026) compared with 92% (953 of 1030) with US-GB (P = .002). The negative predictive value (NPV) for both biopsy methods was moderate but significantly higher for CEUS-GB than for US-GB (74% vs 57%, P = .001). The difference was remarkable for lesions smaller than 2.0 cm, with CEUS-GB showing higher diagnostic accuracy (96% vs 88%, P = .004) and sensitivity (95% vs 87%, P = .007) than US-GB. Among lesions smaller than 2.0 cm, the accuracy of CEUS-GB and US-GB for detection of hepatocellular carcinoma was 93% and 80%, respectively (P = .008), while it was comparable for liver metastases (98% vs 95%, P = .63). Conclusion Contrast-enhanced US-guided biopsy of focal liver lesions is an effective and safe procedure with a higher diagnostic accuracy than US-guided biopsy, especially for lesions smaller than 2.0 cm and for hepatocellular carcinoma diagnosis. Clinical trial registration no. NCT02413437 © RSNA, 2022 Online supplemental material is available for this article.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma Hepatocelular/patologia , Estudos Prospectivos , Meios de Contraste , Estudos Retrospectivos , Ultrassonografia/métodos , Sensibilidade e Especificidade , Neoplasias Hepáticas/patologia , BiópsiaRESUMO
BACKGROUND: Triple-negative breast cancer (TNBC) patients have relatively poor clinical outcomes. A marker predicting the prognosis of patients with TNBC could help guide treatment. Extensive evidence demonstrates that angiopoietin-like 4 (ANGPTL4) is involved in the regulation of cancer growth, metastasis and angiogenesis. Therefore, its role in TNBC is of interest. METHODS: We tested the ANGPTL4 expression level in tumor tissues by immunohistochemistry (IHC) and detected its association with the clinical features of TNBC patients. Next, the effects and mechanisms of ANGPTL4 on TNBC cell migration and adhesion were investigated. RESULTS: We found that ANGPTL4 overexpression was associated with favorable outcomes in TNBC patients. ANGPTL4 upregulation inhibited cell adhesion, migration and invasion in vitro. Further analyses demonstrated that the possible mechanism might involve suppression of TNBC progression by interacting with extracellular matrix-related genes. CONCLUSIONS: The present findings demonstrated that enhancement of ANGPTL4 expression might inversely correlate with TNBC progression. ANGPTL4 is a promising marker of TNBC and should be evaluated in further studies. TRIAL REGISTRATION: Retrospectively registered.
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Proteína 4 Semelhante a Angiopoietina/genética , Prognóstico , Neoplasias de Mama Triplo Negativas/genética , Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
AIM: To study the expression and prognostic significance of CD80 in patients with gastric adenocarcinoma. Materials & methods: Real-time quantitative PCR, western blot and immunohistochemistry were performed to detect the expression of CD80 in gastric cancer tissues and matched adjacent normal tissues. Double immunohistochemical staining was performed to preliminary examine the relationship between CD80+ cells and CD8+ cytotoxic T lymphocytes. RESULTS: The expression of CD80 was downregulated in tumor tissues compared with normal tissues (p = 0.002). Immunohistochemistry analysis showed that 49 (39.8%) of 123 patients with gastric cancer demonstrated reduced CD80 expression, which was correlated with the tumor differentiation grade. CONCLUSION: Our data suggest that reduced CD80 expression independently predicts a poor prognosis in patients with gastric adenocarcinoma.
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Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Antígeno B7-1/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Antígeno B7-1/genética , Biomarcadores Tumorais , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
2,5-Furandicarboxylic acid (FDCA) is a bio-based platform chemical for the production of polyethylene furanoate (PEF) and other valuable furanic chemicals. A magnetic laccase catalyst with (2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (TEMPO) as the mediator has the remarkable capability of oxidizing 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA). Under optimal reaction conditions, a quantitative yield (90.2 %) of FDCA with complete HMF conversion was obtained after 96â h of reaction. More importantly, the magnetic laccase catalyst exhibited good recyclability and stability, maintaining 84.8 % of its original activity following six reuse cycles. This is the first report on the efficient catalytic oxidation of HMF to FDCA by using an immobilized enzyme catalyst.
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Ácidos Dicarboxílicos/síntese química , Enzimas Imobilizadas/química , Furaldeído/análogos & derivados , Furanos/síntese química , Lacase/química , Nanopartículas de Magnetita/química , Biocatálise , Óxidos N-Cíclicos/química , Furaldeído/química , Química Verde/métodos , Oxirredução , Dióxido de Silício/químicaRESUMO
An efficient strategy for laccase production in Trametes versicolor cultures was developed using vanillic acid as the inducer. The optimized vanillic acid treatment strategy consisted of exposing 2-day-old mycelia cultures to 80 mg/L vanillic acid. After 4 days, laccase activity of 588.84 U/L was achieved in flasks which represented a 1.79-fold increase compared to the control. In 200-L airlift bioreactor, the maximal laccase activity reached up to 785.12 U/L using the optimized vanillic acid treatment strategy. The zymograms of culture supernatants revealed three bands with laccase activity, among which Lac1 and Lac2 were abundant laccase isoforms constitutively expressed, and Lac3 was an inducible isozyme by vanillic acid. The results of real-time quantitative PCR showed that the transcription level of lcc in T. versicolor cultures grown with vanillic acid for 7 days was about 5.64-fold greater than that without vanillic acid in flasks. In 200-L airlift bioreactor cultures of T. versicolor with addition of vanillic acid, the transcript level of lcc at day 7 was 2.62-fold higher than that in flasks with vanillic acid due to the good mass transfer and oxygen supply in the bioreactor system. This study provides a basis for understanding the induction mechanism of vanillic acid for laccase production and has good potential for industrial applications.
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Lacase/biossíntese , Trametes/efeitos dos fármacos , Ácido Vanílico/farmacologia , Biomassa , Reatores Biológicos , Eletroforese em Gel de Poliacrilamida Nativa , Reação em Cadeia da Polimerase em Tempo Real , Trametes/metabolismoRESUMO
BACKGROUND: This study was conducted to evaluate the chemical composition of eight types of urinary calculi using spiral computerized tomography (CT) in vivo. METHODS: From October 2011 to February 2013, upper urinary tract calculi were obtained from 122 patients in the department of urinary surgery of the First Affiliated Hospital of Soochow University. All patients were scanned with a 64-detector row helical CT scanner using 6.50 mm collimation before ureterorenoscopy. Data from the preoperative spiral CT scans and postoperative chemical composition of urinary calculi were collected. RESULTS: The chemical composition analysis indicates that there were five types of pure calculi and three types of mixed calculi, including 39 calcium oxalate calculi, 12 calcium phosphate calculi, 10 calcium carbonate calculi, 8 magnesium ammonium phosphate calculi, 6 carbonated apatite, 21 uric acid/ammonium urate calculi, 10 uric acid/calcium oxalate calculi, and 16 calcium oxalate/calcium phosphate calculi. There were significant differences in the mean CT values among the five types of pure calculi (P < 0.001). Furthermore, we also observed significant differences in the mean CT values among three types of mixed calculi (P < 0.001). Significant differences in the mean CT values were also found among eight types of urinary calculi (P < 0.001). However, no statistically significant difference was observed between the mean CT values of magnesium ammonium phosphate calculi and uric acid/calcium oxalate calculi (P = 0.262). CONCLUSION: Our findings suggest that spiral CT could be a promising tool for determining the chemical composition of upper urinary tract calculi.
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Tomografia Computadorizada Espiral/métodos , Cálculos Urinários/química , Cálculos Urinários/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ânions/análise , Ânions/química , Compostos de Cálcio/análise , Compostos de Cálcio/química , China , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Úrico/análise , Ácido Úrico/química , Adulto JovemRESUMO
BACKGROUND: MiR-133b is a muscle-specific microRNA; it has a role in the formation of cardiocytes and the expression of myocardium ion channels by regulating target genes. Many human malignant tumors demonstrate a low expression of miR-133b, as noted in colorectal, lung, esophagus and bladder cancers, but the role of miR-133b in bladder cancer is unknown. METHODS: The expression of miR-133b in clinical bladder cancer specimens and adjacent normal tissues was confirmed by stem-loop RT-PCR. We also analyzed the relationship between miR-133b expression and clinicopathological factors of bladder cancer. Bcl-w and Akt1 protein expression in 41 bladder cancer specimens and adjacent normal tissues was detected by Western blot. After transfection of miR-133b mimics or inhibitor into a T24 human bladder cancer cell line, Bcl-w and Akt1 protein and mRNA expression were examined by Western blot and RT-PCR, respectively. The effect of miR-133b on T24 cell proliferation and apoptosis was measured by CCK-8 tests and flow cytometry, respectively. RESULTS: The expression of miR-133b in bladder cancer tissues from 41 patients was significantly down-regulated (P < 0.01); low expression of miR-133b was strongly associated with high-grade bladder cancer (P < 0.01). Bcl-w and Akt1 proteins were significantly overexpressed in bladder cancer tissues versus adjacent normal tissues (P < 0.01 for both). The expression of Akt1 and Bcl-w proteins and Akt1 mRNA, in T24 cells was significantly down-regulated or up-regulated after transfection of miR-133b mimics or inhibitor, respectively; however, there was no significant difference in Bcl-w mRNA expression. Transfection of HEK-293 T cells with miR-133b significantly suppressed a luciferase-reporter containing the Bcl-w or Akt 1 3'-untranslated regions. MiR-133b mimics significantly inhibited T24 cell proliferation, as well as increased T24 cell apoptosis (P < 0.05 and P < 0.01, respectively) while the miR-133b inhibitor increased and decreased these, respectively (P < 0.05 for both). CONCLUSIONS: MiR-133b may play a very important role in the proliferation and apoptosis of T24 cells by regulating the expression of Bcl-w and Akt1.
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BACKGROUND: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma in which the upper aerodigestive tract is the most commonly involved site. To date, optimal treatment strategies and prognosis for patients with ENKTL have not been fully defined. METHODS: This prospective study was conducted to evaluate the efficacy and safety profiles of first-line combined gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE ENKTL. The primary endpoints were the complete response rate, the objective response rate, and toxicities. Secondary endpoints were overall survival and progression-free survival. RESULTS: Twenty-seven patients with newly diagnosed ENKTL were enrolled and completed the entire course of treatment. At the end of treatment, the overall response rate was 96.3%, including 20 patients (74.1%) who attained a complete response and 6 patients (22.2%) who attained a partial response. No patients developed disease progression during therapy. Grade 1 and 2 toxicities were frequent during GELOX, but grade 3 and 4 toxicities were few, and no treatment-related deaths occurred. At a median follow-up of 27.37 months, 7 patients (25.9%) experienced disease progression, and 4 of those patients died of disease. The rates of 2-year overall and progression-free survival were both 86%, and patients who attained a complete response at the end of treatment had significantly longer progression-free survival (P = .012) and overall survival (P = .021) than patients who did not attain a complete response. CONCLUSIONS: The current results indicated that GELOX followed by involved-field radiation therapy can be an effective and feasible treatment strategy for patients with stage IE/IIE ENKTL of the upper aerodigestive tract. These results will require further investigation in larger prospective trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Quimioterapia de Indução , Linfoma Extranodal de Células T-NK/terapia , Adulto , Idoso , Hidróxido de Alumínio/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bentonita/administração & dosagem , Quimiorradioterapia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/patologia , Hidróxido de Magnésio/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem , GencitabinaRESUMO
OBJECTIVE: To investigate the effects of atorvastatin on advanced glycation end products (AGE) induced monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells (HUVECs) and whether this effect could be linked to peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor-κB (NF-κB). METHODS: Grouping: (1) Blank control group; (2) BSA group; (3) AGE group: cells were incubated with different concentrations of AGE (10(-4), 10(-3), 10(-2) and 10(-1) g/L) for 24 hours; (4) AGE + Atorvastatin group: cells were incubated with different concentrations of atorvastatin (0.1, 1, 10 µmol/L) for 1 hour, then incubated with AGE (10(-1) g/L) for 24 hours; (5) PPAR-γ agonist (15 d-PGJ2) group: cells were incubated with 15 d-PGJ2 (10 µmol/L) for 1 hour, then incubated with AGE (10(-1) g/L) for 24 hours; (6) PPAR-γ inhibitor (GW9662) group: cells were incubated with GW9662 (5000 nmol/L) for 1 hour, then incubated with atorvastatin (1 µmol/L) and AGE (10(-1) g/L) for 24 hours. Collagenase was used to isolate the endothelial cell from human umbilical vein; RT-PCR was performed to examine the mRNA expression of MCP-1 and PPAR-γ; Western blot was performed to detect NF-κB p65 protein. RESULTS: (1) The expression of MCP-1 mRNA was increased in proportion with increasing concentrations of AGEs which could be blocked by atorvastatin in a dose-dependent manner. (2) AGE (10(-1) g/L) significantly downregulated the expression of PPAR-γ mRNA (0.22 ± 0.08 vs. 0.69 ± 0.09, P < 0.01) while upregulated the expression of phospho-NF-κB p65 protein (0.78 ± 0.06 vs. 0.31 ± 0.01, P < 0.01) and nonphospho-NF-κB p65 protein (1.61 ± 0.16 vs. 0.59 ± 0.14, P < 0.01) compared with the control group which could be significantly attenuated by atorvastatin. (3) PPAR-γ agonist decreased the expression of phospho-NF-κB p65 protein (0.21 ± 0.01 vs. 0.78 ± 0.06, P < 0.01), nonphospho-NF-κB p65 protein (0.67 ± 0.14 vs. 1.61 ± 0.16, P < 0.01) and MCP-1 mRNA (0.17 ± 0.02 vs. 0.93 ± 0.12, P < 0.01) compared with AGE (10(-1) g/L) group. (4) PPAR-γ inhibitor antagonized the effect of atorvastatin on the expression of phospho-NF-κB p65 protein, nonphospho-NF-κB p65 protein and MCP-1 mRNA stimulated by AGE in HUVECs (P < 0.01). CONCLUSION: The anti-inflammatory properties of atorvastatin in AGE stimulated HUVECs may partly be attributed to the effect on upregulation of PPAR-γ and downregulation of NF-κB signaling pathway.
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Quimiocina CCL2/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Ácidos Heptanoicos/farmacologia , Pirróis/farmacologia , Atorvastatina , Células Cultivadas , Quimiocina CCL2/genética , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , PPAR gama/metabolismo , RNA Mensageiro/genética , Transdução de Sinais , Fator de Transcrição RelA/metabolismoRESUMO
To investigate the diversity and distribution of rhizobia associated with Sophora davidii in habitats with different light and soil conditions at the Loess Plateau, we isolated rhizobia from root nodules of this plant grown at 14 sites at forest edge or understory in Shaanxi Province. Based on PCR-RFLP and phylogenies of 16S rRNA gene, housekeeping genes (atpD, dnaK, recA), and symbiosis genes (nodC and nifH), a total of 271 isolates were identified as 16 Mesorhizobium genospecies, belonging to four nodC lineages, and three nifH lineages. The dominance of M. waimense in the forest edge and of M. amorphae/Mesorhizobium sp. X in the understory habitat evidenced the illumination as a possible factor to affect the diversity and biogeographic patterns of rhizobia. However, the results of Canonical Correlation Analysis (CCA) among the environmental factors and distribution of rhizobial genospecies illustrated that soil pH and contents of total phosphorus, total potassium and total organic carbon were the main determinants for the community structure of S. davidii rhizobia, while the illumination conditions and available P presented similar and minor effects. In addition, high similarity of nodC and nifH genes between Mesorhizobium robiniae and some S. davidii rhizobia under the forest of Robinia pseudoacacia might be evidence for symbiotic gene lateral transfer. These findings firstly brought an insight into the diversity and distribution of rhizobia associated with S. davidii, and revealed illumination conditions a possible factor with impacts less than the soil traits to drive the symbiosis association between rhizobia and their host legumes.
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Rhizobium/classificação , Sophora , China , DNA Bacteriano/genética , Ecossistema , Florestas , Genes Bacterianos , Variação Genética , Filogenia , RNA Ribossômico 16S/genética , Rhizobium/isolamento & purificação , Nódulos Radiculares de Plantas/microbiologia , Solo , Microbiologia do Solo , Sophora/microbiologia , SimbioseRESUMO
Alkyl carboxylic acids as well as primary amines are ubiquitous in all facets of biological science, pharmaceutical science, chemical science and materials science. By chemical conversion to redox-active esters (RAE) and Katritzky's N-alkylpyridinium salts, respectively, alkyl carboxylic acids and primary amines serve as ideal starting materials to forge new connections. In this work, a Mn-mediated reductive decarboxylative/deaminative functionalization of activated aliphatic acids and primary amines is disclosed. A series of C-X (X = S, Se, Te, H, P) and C-C bonds are efficiently constructed under simple and mild reaction conditions. The protocol is applicable to the late-stage modification of some structurally complex natural products or drugs. Preliminary mechanistic studies suggest the involvement of radicals in the reaction pathway.
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Aminas/química , Técnicas de Química Sintética/métodos , Ácidos Graxos/química , Manganês/química , Catálise , Estudos de Viabilidade , OxirreduçãoRESUMO
Immune checkpoint blockade of programmed cell death protein 1 (PD-1) had an impressive long-lasting effect in a portion of advanced-stage melanoma patients, however, this therapy failed to induce responses in several patients; how to increase the objective response rate is very important. Cellular FLICE-inhibitory protein (c-FLIP) could inhibit apoptosis directly at the death-inducing signaling complex of death receptors and is also considered to be the main cause of immune escape. The overexpression of c-FLIPL occurs frequently in melanoma and its expression is associated with the prognosis. We found that the level of c-FLIPL expression was associated with the PD-1 blockade response rate in melanoma patients. Thus, we performed this research to investigate how c-FLIPL regulates immunotherapy in melanoma. We demonstrate that down regulation of c-FLIPL enhances the PD-1 blockade efficacy in B16 melanoma tumor model. Down regulation of c-FLIPL could increase the tumor apoptosis and enhance the antitumor response of T cells in the lymphocyte tumor cells co-culture system. Moreover, knockdown of c-FLIPL could decrease the expression of PD-L1 and recruit more effector T cells in the tumor microenvironment. Our results may provide a new combined therapeutic target for further improving the efficacy of PD-1 blockade in melanoma.
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Coenzyme Q10 (CoQ10) is an important component of the respiratory chain in humans and some bacteria. As a high-value-added nutraceutical antioxidant, CoQ10 has excellent capacity to prevent cardiovascular disease. The content of CoQ10 in the industrial Rhodobacter sphaeroides HY01 is hundreds of folds higher than normal physiological levels. In this study, we found that overexpression or optimization of the synthetic pathway failed CoQ10 overproduction in the HY01 strain. Moreover, under phosphate- limited conditions (decreased phosphate or in the absence of inorganic phosphate addition), CoQ10 production increased significantly by 12% to220 mg/L, biomass decreased by 12%, and the CoQ10 productivity of unit cells increased by 27%. In subsequent fed-batch fermentation, CoQ10 production reached 272 mg/L in the shake-flask fermentation and 1.95 g/L in a 100-L bioreactor under phosphate limitation. Furthermore, to understand the mechanism associated with CoQ10 overproduction under phosphate- limited conditions, the comparatve transcriptome analysis was performed. These results indicated that phosphate limitation combined with glucose fed-batch fermentation represented an effective strategy for CoQ10 production in the HY01. Phosphate limitation induced a pleiotropic effect on cell metabolism, and that improved CoQ10 biosynthesis efficiency was possibly related to the disturbance of energy metabolism and redox potential.
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Besides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it has not been used for the detection of small molecules. Bacterial allosteric transcription factors (aTFs) have evolved to sense and respond sensitively to a variety of small molecules to benefit bacterial survival. By combining the single-stranded DNA cleavage ability of CRISPR-Cas12a and the competitive binding activities of aTFs for small molecules and double-stranded DNA, here we develop a simple, supersensitive, fast and high-throughput platform for the detection of small molecules, designated CaT-SMelor (CRISPR-Cas12a- and aTF-mediated small molecule detector). CaT-SMelor is successfully evaluated by detecting nanomolar levels of various small molecules, including uric acid and p-hydroxybenzoic acid among their structurally similar analogues. We also demonstrate that our CaT-SMelor directly measured the uric acid concentration in clinical human blood samples, indicating a great potential of CaT-SMelor in the detection of small molecules.
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Proteínas Associadas a CRISPR , Sistemas CRISPR-Cas , Endodesoxirribonucleases , Fatores de Transcrição , Regulação Alostérica , Bioensaio , Clostridiales , Humanos , Limite de Detecção , Motivos de Nucleotídeos , Parabenos , Biologia Sintética , Ácido Úrico/sangueRESUMO
The over expression of fatty acid synthase (FAS), a key enzyme in biosynthesis of fatty acid, can enhance enzyme activity and result in the malignant behavior, special material metabolism and energy metabolism of tumors. The expression of FAS is significantly higher in prostate cancer than in normal prostate tissues, which shows that FAS can be used as a marker in the early diagnosis of prostate cancer. The abnormally increased expression of FAS in prostate cancer may offer a new target for the drug treatment of the disease.
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Ácido Graxo Sintases/metabolismo , Neoplasias da Próstata/enzimologia , Biomarcadores Tumorais/metabolismo , Diagnóstico Precoce , Humanos , Masculino , Neoplasias da Próstata/diagnósticoRESUMO
As the first fungal quorum sensing molecule, farnesol-induced morphological transition is usually studied in dimorphic fungi, but in basidiomycetes the morphological changes regulated by farnesol are rarely investigated. In this study, we found that farnesol made the basidiomycete Coriolus versicolor develop into a hyperbranched morphology with short hyphae and bulbous tips. Farnesol treatment resulted in a significant increase of intracellular oxidative stress level, which influenced the expression of several morphogenesis-related genes, and thereby led to the morphological changes. High oxidative stress level significantly stimulated the expression of laccase genes for improving intracellular laccase biosynthesis. The resulted hyperbranched morphology further accelerated the secretion of intracellular laccase into culture medium. As a result, extracellular laccase production reached a maximum of 2189.2 ± 54.7 U/L in farnesol-induced cultures, which was 6.8-fold greater than that of control cultures. SDS-PAGE and native-PAGE showed that farnesol increased laccase production by promoting the biosynthesis of three laccase isoforms. Together these results provide new opportunities in not only understanding the farnesol-regulated mycelial morphology in basidiomycetes, but also developing novel strategies for enhancing the production of secreted enzymes of biotechnological interest.
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Agaricales/fisiologia , Farneseno Álcool/farmacologia , Hifas/fisiologia , Agaricales/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Genes Fúngicos , Dissulfeto de Glutationa/metabolismo , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Lacase/metabolismo , Morfogênese/efeitos dos fármacos , Morfogênese/genética , Espécies Reativas de Oxigênio/metabolismo , Fatores de TempoRESUMO
Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is an uncommon extranodal non-Hodgkin's lymphoma (NHL), which was traditionally treated with anthracycline-containing regimens followed by consolidative radiation therapy (RT) to add therapeutic benefits. The introduction of anti-CD20 antibody rituximab for the treatment of B-cell NHLs has significantly improved the clinical outcome of these malignant diseases. It is unclear, however, whether consolidative RT could still add therapeutic benefits for PB-DLBCL patients treated with rituximab. To answer this important question, we used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the impact of RT on the clinical outcomes of PB-DLBCL patients in the rituximab era. Information on patient age, year of diagnosis, stage, race, laterality, and RT status for PB-DLBCL patients diagnosed between 2001 and 2014 were extracted. Kaplan-Meier survival curves were plotted, and log-rank test was used to compare the potential survival difference. Multivariate analysis using Cox proportional hazards model was employed to determine the impact of RT and other factors such as age, race, tumor laterality, stage, and year of diagnosis on survival. Among the 386 patients identified, the median follow-up time was 45 months (range, 0-167 months); the median age was 64 years (range, 19-93 years); 33.9% of the patients were younger than 60 years of age; 69.9% of the patients were stage I; 79.0% were white; 51.8% received RT. The 5-year OS and cause-specific survival (CSS) for the whole cohort were 72.3% and 82.5%, respectively. The 5-year OS was significantly superior for patients who received RT compared to those who did not receive RT (78.1% vs. 66.0%, P = 0.031). In multivariable analysis, RT remained significantly associated with improved OS (P = 0.026). In summary, our study suggests that RT still adds significant therapeutic benefits for patients with PB-DLCBL in the rituximab era.
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Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/terapia , Quimiorradioterapia/métodos , Linfoma Difuso de Grandes Células B/terapia , Rituximab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rituximab/uso terapêutico , Programa de SEER , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the diagnosis, treatment and prognosis of sarcoma of the adult prostate. METHODS: We reported 6 cases of sarcoma of the adult prostate, of which 3 were leiomyosarcoma, 2 rhabdomyosarcoma and 1 malignant neurilemoma, 2 at Ghavimi Stage II, 3 at Stage III and 1 at Stage IV. The patients were aged from 18 to 44 years (mean 31 years) and their disease course ranged from 3 to 12 months (mean 7 months). Five of them received operation, radiotherapy and / or chemotherapy and 1 underwent cystostomy only. RESULTS: Immunohistochemical dyeing showed vimentin to be positive while PSA and PAP negative in all the 6 cases, actin (HHF35) positive in the cases of leiomyosarcoma and rhabdomyosarcoma, and S-100 and lysozyme positive in the case of malignant neurilemoma. One case failed to be followed up, and the other 5 died 2-11 months after the operation. CONCLUSION: Sarcoma of the adult prostate initiates with the symptom of progressive dysuria, which can be diagnosed by DRE test and confirmed by needle biopsy. Early diagnosis and radical surgical resection may offer the best chance of survival, but with poor prognosis.
Assuntos
Neoplasias da Próstata/terapia , Sarcoma/terapia , Actinas/análise , Adolescente , Adulto , Terapia Combinada , Cistostomia , Tratamento Farmacológico , Evolução Fatal , Humanos , Imuno-Histoquímica , Masculino , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Radioterapia , Proteínas S100/análise , Sarcoma/diagnóstico , Sarcoma/metabolismo , Vimentina/análiseRESUMO
A novel strategy of exposing 2-day-old mycelia cultures to 0.8mM farnesol was developed to stimulate extracellular polysaccharide (EPS) production in Trametes versicolor submerged cultures. Farnesol, a quorum sensing molecule in fungi, could significantly increase EPS production by promoting polysaccharide biosynthesis and regulating mycelial morphology. EPS yield reached a maximum of 2.56g/L that was 2.7-fold greater than that of control cultures. Farnesol made T. versicolor develop into fluffy, loose and multi-hyphae morphology, which facilitated the excretion of intracellular polysaccharide into culture medium. Moreover, EPS from farnesol-induced cultures (EPS-F) with higher carbohydrate and uronic acid contents mainly contained high molecular weight polysaccharide (134kDa, 85%), and comprised glucose, mannose and galactose in a molar ratio of 34.2:2.1:1.0. These physicochemical properties led to stronger antioxidant and antitumor activities of EPS-F. This is the first report that farnesol can significantly improve the production of polysaccharide with higher biological activities. It provides a novel strategy to enhance the production and bioactivity of mushroom polysaccharide using microbial quorum sensing molecules.
Assuntos
Espaço Extracelular/efeitos dos fármacos , Farneseno Álcool/farmacologia , Polissacarídeos Fúngicos/biossíntese , Polissacarídeos Fúngicos/farmacologia , Percepção de Quorum , Trametes/citologia , Trametes/efeitos dos fármacos , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Espaço Extracelular/metabolismo , Células HeLa , Humanos , Percepção de Quorum/efeitos dos fármacos , Trametes/metabolismoRESUMO
Graphene as a 2-dimentional material has been widely used in the field of biomedical applications. In this study, molecular dynamics simulations are carried out on the fibrinopeptide-A and graphene surfaces with N and O modifications. A new set of parameters for the CHARMM force field are developed to describe the behaviors of the surfaces. Our results indicate that the existence of most oxygen and nitrogen groups may enhance the interaction between the surfaces and the peptide, whereas the substitutional nitrogen on the graphene surface does not make a big difference. The improvement of interaction is not only because of the functional group on the surface, but also the defective morphology. The defective morphology also clears away the surface water layer. Our results suggest that the interactions between graphene biomolecules can be affected by functionalizing the surface with different types of functional groups, which is in accordance with the theory of material design.