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1.
Int J Clin Oncol ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062731

RESUMO

BACKGROUND: To investigate the survival outcomes of stage IB1 cervical cancer patients with tumor size ≤ 2 cm who underwent laparoscopic or abdominal radical hysterectomy. METHODS: We retrospectively analyzed stage IB1 cervical cancer patients with a tumor size ≤ 2 cm who underwent laparoscopic or abdominal radical hysterectomy in China between 2004 and 2016. A real-world study (RWS) and 1:1 matching was used in the study. RESULTS: After 1:1 matching, laparoscopic (n = 926) and abdominal radical hysterectomy (n = 926) had similar 5-year overall survival and disease-free survival rates in stage IB1 cervical cancer with a tumor size ≤ 2 cm. Subsequently, in cervical squamous carcinoma with tumor size ≤ 2 cm, the laparoscopic and abdominal groups (724 cases, respectively) showed comparable 5-year overall survival and disease-free survival rates. Finally, in cervical adenocarcinoma or adenosquamous carcinoma with tumor size ≤ 2 cm, the laparoscopic group (n = 174) had a similar 5-year overall survival rate but a lower disease-free survival rate compared to those of the abdominal group (disease-free survival: 89.9% vs. 98.0%, respectively, P = 0.006; hazard ratio (HR), 5.094; 95% confidence interval (CI), 1.400-18.535; P = 0.013; n = 174). The RWS results were similar to the 1:1 matching results. CONCLUSIONS: Patients with squamous cell carcinoma in stage IB1 cervical cancer with tumor size ≤ 2 cm might be suitable for laparoscopic surgery, while patients with adenocarcinoma or adenosquamous carcinoma with tumor size ≤ 2 cm are not candidates for laparoscopic surgery.

2.
AAPS J ; 22(2): 38, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31997095

RESUMO

Blood-based soluble protein biomarkers provide invaluable clinical information about patients and are used as diagnostic, prognostic, and pharmacodynamic markers. The most commonly used blood sample matrices are serum and different types of plasma. In drug development research, the impact of sample matrix selection on successful protein biomarker quantification is sometimes overlooked. The sample matrix for a specific analyte is often chosen based on prior experience or literature searches, without good understanding of the possible effects on analyte quantification. Using a data set of 32 different soluble protein markers measured in matched serum and plasma samples, we examined the differences between serum and plasma and discussed how platelet or immune cell activation can change the quantified concentration of the analyte. We have also reviewed the effect of anticoagulant on analyte quantification. Finally, we provide specific recommendations for biomarker sample matrix selection and propose a systematic and data-driven approach for sample matrix selection. This review is intended to raise awareness of the impact and considerations of sample matrix selection on biomarker quantification.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31702013

RESUMO

CONTEXT: Gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) have been widely used to treat idiopathic central precocious puberty (CPP) or early and fast puberty (EFP). However, large-scale studies to evaluate the treatment effects on final adult height (FAH) are still lacking. OBJECTIVE: To assess the effects of long-term treatment for CPP/EFP on FAH and its main influencing factors. DESIGN AND SETTING: Retrospective, multi-center observational study from 1998-2017. PARTICIPANTS: Four hundred forty-eight Chinese girls with CPP/EFP received GnRHa and rhGH treatment (n=118), GnRHa alone (n=276), or no treatment (n=54). MAIN OUTCOME MEASURES: FAH, target height (Tht), and predictive adult height (PAH). RESULTS: The height gain (FAH-PAH) was significantly different among the GnRHa and rhGH treatment, GnRHa alone, and no treatment groups (p<0.05; 9.51±0.53, 8.07±0.37, and 6.44±0.91 cm, respectively). The genetic height gain (FAH-Tht) was 4.0±0.5 cm for the GnRHa+rhGH group and 2.0±0.27 cm for the GnRHa group, while the control group reached their Tht. In addition, five critical parameters derived from PAH, bone age, and Tht, showed excellent performance in predicting which patients could gain ≥5 cm (FAH-PAH), and this was further validated using an independent study. CONCLUSIONS: The overall beneficial effect of GnRHa+rhGH or GnRHa on FAH was significant. The control group also reached their genetic target height. Clinicians are recommended to consider both the potential gains in height and the cost of medication.

4.
Mol Nutr Food Res ; 63(24): e1900612, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31703241

RESUMO

SCOPE: Vegetarian diets confer health benefits to many cardiometabolic diseases, although whether and how gut microbiota in vegetarians contributes to host metabolism remains unclear. Thus, the aim is to explore the possible links between the gut microbiota and circulating gut microbiota-host co-metabolites among vegetarians and omnivores. METHODS AND RESULTS: Fecal and serum samples from 36 adults following a vegan, lacto-ovo vegetarian, or omnivorous diet are collected. A 16S rRNA gene, metagenome, metatranscriptome, and metabolome integrated multi-omics approach is adopted to profile fecal microbial composition and functionality and circulating gut microbiota-host co-metabolites. 16S rRNA gene and metagenomic sequencing suggest a significant difference in gut microbial composition between the two vegetarian groups and the omnivorous group at the family, genus, and species level. Metabolomic analysis reveals that circulating branched-chain amino acids (BCAAs)-valine, leucine, and isoleucine-are significantly lower in the two vegetarian groups than those in the omnivorous group. In line with the lower concentrations of BCAAs, metatranscriptomic analysis shows that the gut microbial pathway for the degradation of BCAAs is significantly upregulated among vegetarians compared with the omnivores. CONCLUSIONS: The results indicate that gut microbiota plays an important role in the modulation of circulating BCAAs among vegetarians.

5.
EBioMedicine ; 48: 81-91, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31631041

RESUMO

BACKGROUND: Histological assessment of resected margins has some drawbacks. We therefore aimed to identify a panel of metabolic markers for evaluating the surgical margins of oral squamous cell carcinoma during surgery. METHODS: A total of 28 case of OSCC samples were enrolled in the study. Gas chromatography-mass spectrometry based untargeted metabolic analysis was employed to acquire the metabolic perturbation of the distance-related surgical margins in the development group. The acquired MS data were then subjected to univariate and multivariate analysis by MetaboAnalyst. Ultra-high performance liquid chromatography-tandem mass spectrometerbased targeted metabolomics for quantitative analysis of the validation group was performed to verify the results of the development group. Another 60 OSCC patients with dysplastic surgical margins were used to further validate the results of the development group by immunohistochemical examination of key enzyme expression, and correlate them with clinicopathological parameters and clinical outcomes. FINDINGS: We finally identified 4 amino acids as negative margin markers, and 6 amino acids as dysplastic margin markers. IHC analysis showed that asparagine synthetase positive expression in dysplastic surgical margins and its higher expression was correlated with tumor recurrence and local relapse-free survival. INTERPRETATIONS: We developed a panel of metabolic molecular markers to supplement the evaluation of negative and dysplastic margins. FUND: This study was supported by Nanjing Municipal Key Medical Laboratory Constructional Project Funding (Since 2012); Center of Nanjing Clinical Medicine Tumor (Since 2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

6.
Zhongguo Zhong Yao Za Zhi ; 44(14): 3022-3034, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602849

RESUMO

To characterize the chemical constituents of Huanbei Zhike Prescription by ultra-high performance liquid chromatography-time of flight mass spectrometry( UPLC-Q-TOF-MS/MS). A Thermo Syncronls C18 column( 2. 1 mm×100 mm,1. 7 µm) was used with methanol( A)-0. 1% formic acid solution( B) as the mobile phase for gradient elution. The injection volume was 2 µL; the column temperature was 40 ℃; the flow rate was 0. 3 m L·min-1; and electrospray ionization( ESI) source was used to collect data in positive and negative ion modes. The ion scanning range was m/z 50-1 200,with capillary voltage of 3 000 V,ion source temperature of100 ℃,atomization gas flow rate of 50 L·h-1,desolvent gas flow rate of 800 L·h-1,desolvent temperature of 400 ℃,cone hole voltage of 40 V,with argon as the collision gas and the collision energy was 20-35 V. The excimer ion peak information was analyzed by Waters UNIFI data processing software. The molecular formula with error within 1×10-5 was compared with the data in database to identify the compounds. The secondary fragment ion information of the target compound was selected,and then compared with the retention time and fragmentation patterns provided by the database and the existing literature to further confirm the compositions and structures of the compounds. A total of 68 main compounds in Huanbei Zhike Prescription were identified,including 38 flavonoids,10 organic acids,6 terpenoids and 10 nitrogen-containing compounds,of which 12 compounds were verified by the control substances. This method is rapid and accurate,which provides a new strategy for the qualitative analysis of the chemical constituents of Huanbei Zhike Prescription,and lays a foundation for the further study and quality control of the compound pharmacodynamic substance.


Assuntos
Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Espectrometria de Massas em Tandem , Terpenos/análise
7.
Biomater Sci ; 7(12): 5270-5282, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603446

RESUMO

To ensure site-specific drug delivery/release in tumor cells and cancer-associated fibroblasts (CAFs) and reduce the systemic toxicity of chemotherapy, a novel drug delivery system called human serum albumin-indocyanine green-cisplatin nanoparticles (HSA-ICG-DDP NPs) was developed in our study. We characterized this system in vitro and in vivo and showed synergistic effects with photodynamic therapy (PDT), photothermal therapy (PTT) and chemotherapy; thereby it can significantly improve therapeutic efficacy compared with cancer monotherapy. High expression of secreted protein acidic and rich in cysteine (SPARC) in oral squamous cell cancer (OSCC) and CAFs was also confirmed in our study. Our study also found that the cellular uptake of HSA-ICG-DDP NPs in tumor cells and CAFs can be enhanced by SPARC-mediated endocytosis. Cisplatin (DDP) release from the NPs in the tumor site can be precisely triggered by the cleavage of the coordination bond of ICG-DDP via a near infrared (NIR)-induced photothermal effect of ICG. Treatment with HSA-ICG-DDP NPs induced generation of reactive oxygen species (ROS) and cytotoxicity in SPARC-highly expressed tumor and CAFs. On in vivo treatment, HSA-ICG-DDP NPs were accumulated within the tumor tissue, where they exhibited stronger antitumor effects, compared to treatment with ICG, HSA-ICG and DDP. Therefore, this novel NIR-triggered drug release system displays potential for the improvement of OSCC treatment through its synergistic effects of PTT/PDT and chemotherapy.

8.
Pathol Oncol Res ; 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606786

RESUMO

Tumor-infiltrating immune cells engage in an extensive crosstalk with tumors and act as two-edged swords by inhibiting or promoting cancer growth. Therefore, identifying the density and prognostic values of tumor-infiltrating immune cells will provide valuable tips for cancer treatments. In this study, we identified the density of tumor inflammatory infiltrates and the number of tumor-infiltrating immune cells, including CD3+, CD4+, CD8+, FoxP3+ T cells and CD1a+ dendritic cells (DCs) in 153 tongue squamous cell carcinomas (TSCC). High inflammatory cell infiltration was associated with better overall survival (OS) and disease free survival (DFS). Moreover, the number of CD3+, CD4+, FoxP3+ and CD1a+ cells were associated with tumor differentiation (P<0.001) and the number of FoxP3+, CD1a+ cells and CD8+/FoxP3+ ratios were also associated with tumor stage (P<0.01, P<0.01, P<0.05). In addition, patients with higher CD1a+ DCs had better OS and increased CD8+/FoxP3+ ratios were associated with improved OS and DFS (P = 0.037; P = 0.047; P = 0.033). In conclusion, our results indicated that tumor-infiltrating CD1a+ DCs and CD8+/FoxP3+ ratios were associated with favorable clinical outcomes but not independent prognostic factors for TSCC patients.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31565063

RESUMO

Xueniao capsule, one of the famous traditional Chinese medicine (TCM) formulas, has been proved to be effective for treating acute pyelonephritis (APN) in the clinic. However, the probable mechanisms are still unclear. This study was aimed at investigating the therapeutic effect and action mechanism of Xueniao capsule on acute pyelonephritis rats. Chemical analysis of Xueniao capsule and four different extracts was conducted by HPLC and GC-MS. 21 compounds were identified in the Xueniao capsule, and obvious chemical difference was also revealed among the different extracts by chemical analysis. Metabolomics, combined with bacteriological examination, traditional histopathology, and biochemical parameters, was used to evaluate the effects of Xueniao capsule and four different extracts. After treatment with Xueniao capsule, the bacterial count of urine was decreased and the renal lesions of APN rats were ameliorated by histopathology inspection. Levels of Scr and Ucr, IL-1α, IL-1ß, IL-6, IL-10, CXCL-2, and MCP-1 were decreased significantly, and the reserving effect of Xueniao capsule was superior to the different extracts and norfloxacin. 16 endogenous metabolites related to APN model were revealed, and 12 of them could be reversed by the Xueniao capsule. 1H NMR metabolomic results demonstrated that the formula of Xueniao capsule played the best therapeutic role on APN through regulating energy metabolism and alterations of osmotic pressure. The effect of Xueniao capsule on the APN was the synergistic actions of multiple components, which need to be further investigated in future studies.

10.
Int J Gynecol Cancer ; 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31097513

RESUMO

BACKGROUND: In 2018 the International Federation of Gynecology and Obstetrics (FIGO) revised the staging system of cervical cancer. This study aimed to assess the quality of staging early cervical cancer in China before the revision. METHODS: This multicenter retrospective study included 34 tertiary hospitals in China. Medical records of patients with cervical cancer who underwent primary surgical treatment between January 2010 and December 2015 were reviewed retrospectively. All patients were clinically staged according to the 2009 FIGO staging system. Eligibility criteria included: histopathologically confirmed cervical cancer; 2009 FIGO stage IA-IIA2 based on 2009 FIGO staging system; primary surgical treatment including extrafascial, type II or type III radical hysterectomy; radical trachelectomy; with or without pelvic lymphadenectomy; regardless of surgical route via laparotomy or laparoscopy; and complete clinical and pathological data. Patients who received non-surgical treatment, neoadjuvant treatment, or those with incomplete data were excluded. The accuracy of clinical staging was assessed by comparison between clinical and pathologic stage using the latter as the reference standard. RESULTS: A total of 23 933 cases of cervical cancer were identified and 12 681 fulfilled the inclusion criteria. Of these patients, 69.6% were staged accurately, 9.4% were clinically understaged, and 21.0% were clinically overstaged. The accuracy of stage IA, IB1, IB2, IIA1, and IIA2 was 90.0%, 87.5%, 57.4%, 20.3%, and 25.5%, respectively. The causes of stage inaccuracy were as follows: vaginal involvement (62.3%), maximal tumor diameter (24.6%), extent of cervical stromal invasion (7.1%), parametrial invasion (5.8%), bladder or rectal infiltration (0.1%), and distant metastases (0.1%). CONCLUSION: The accuracy of staging early cervical cancer in China was suboptimal before the revision of the staging system, especially for IIA1 and IIA2. The most common reasons for staging inaccuracy were vaginal involvement and tumor diameter.

11.
Cancer Manag Res ; 11: 3603-3609, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118782

RESUMO

Purpose: To evaluate the impact of pelvic magnetic resonance imaging (MRI) on staging of IB1-IIA2 cervical cancer in routine clinical practice. Patients and Methods: A total of 1,016 patients with IB1-IIA2 cervical cancer who underwent primary surgery and preoperative pelvic MRI between January 2009 and December 2015 were identified in a retrospective multicentre study. Data on clinical stage, MRI reports and surgicopathologic findings were extracted from medical records. The impact of MRI on clinical staging was evaluated by comparison before and after combination of MRI. Using surgicopathologic findings as the reference standard, the impact of pelvic MRI on the accuracy of clinical staging was evaluated. Furthermore, the impact on the accuracy of individual staging parameters such as maximal tumor diameter, vaginal involvement or parametrial infiltration were also evaluated. Results: After combination of pelvic MRI, clinical stage remained unchanged in 59.7%, upstaged in 17.2%, and downstaged in 23.0% of the patients. The overall accuracy of clinical staging increased from 61.0% to 81.4% in our study (P<0.05). As for individual staging parameters, the area under the curve (AUC) for maximal tumor diameter increased from 0.58 to 0.81 (P<0.05). However, the AUC for vaginal involvement decreased from 0.61 to 0.57 (P>0.05). The AUC for parametrial infiltration was also suboptimal (AUC=0.56, P<0.05). Conclusion: In routine clinical practice, MRI could increase the overall accuracy of clinical staging in IB1-IIA2 cervical cancer. For staging parameters, it only significantly increased the accuracy of maximal tumor diameter.

12.
Endokrynol Pol ; 70(4): 318-322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30938833

RESUMO

INTRODUCTION: The aim of this study was to explore the potential role of IL-35 in Graves' disease (GD). MATERIAL AND METHODS: A total of 142 GD patients including 80 newly onset patients, 52 refractory patients and 10 remission patients and 70 normal controls (NCs) were recruited. The messenger RNA (mRNA) expressions of P35 and Epstein-Barr-virus-induced gene 3 (Ebi3) were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Serum level of IL-35 was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression of IL-35mRNA in new onset GD and refractory GD were both significantly higher than NC. Comparison between remission GD and NC showed no significant difference (p > 0.05). A significant increase of Ebi3mRNA expression was observed in new onset GD compared with remission GD (p = 0.030). The new onset GD showed a tendency for increased expression of serum IL-35 but without significant difference. No correlation between IL-35 expression and clinic parameters was found. CONCLUSIONS: Our preliminary observations indicate that IL-35 and CD4+P35+Ebi3+T cells may be involved in the pathogenesis of GD.

13.
Clin Nutr ; 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30876827

RESUMO

BACKGROUND & AIMS: Observational studies have shown that diets high in fat and low in dietary fiber, might have an unfavorable impact on bile acid (BA) profiles, which might further affect host cardiometabolic health. In the current study, we aimed to evaluate the effects of dietary fat content on BA profiles and associated gut microbiota, and their correlates with cardiometabolic risk factors. METHODS: In a randomized controlled-feeding trial, healthy young adults were assigned to one of the three diets: a lower-fat diet (fat 20%, carbohydrate 66% and protein 14%), a moderate-fat diet (fat 30%, carbohydrate 56% and protein 14%) and a higher-fat diet (fat 40%, carbohydrate 46% and protein 14%) for 6 months. All the foods were provided during the entire intervention period. The BA profiles, associated gut microbiota and markers of cardiometabolic risk factors were determined before and after intervention. RESULTS: The higher-fat diet resulted in an elevated concentration of total BAs (p < 0.001), and unconjugated BAs (p = 0.03) compared with lower-fat diet. Secondary BAs, such as deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), 12ketolithocholic acid (12keto-LCA), 3ß-DCA and taurolithocholic acid (TLCA) (p < 0.05 after FDR correction) were significantly increased in the higher-fat diet group after the 6-month intervention. Consistently, the abundances of gut bacteria (Bacteroides, Clostridium, Bifidobacterium and Lactobacillus) which affect bile salt hydrolase gene expression were significantly increased after higher-fat consumption. The change of DCA was positively associated with the relative abundance of Bacteroides (r = 0.31, p = 0.08 after FDR correction). In addition, the changes of fecal concentrations of DCA and 12keto-LCA were positively associated with serum total cholesterol (r > 0.3, p = 0.02 and p = 0.008 after FDR correction, respectively). In line with these findings, serum fibroblast growth factor 19 (FGF19) was marginally significantly elevated in the higher-fat group after intervention (p = 0.05). CONCLUSIONS: The higher-fat diet resulted in an alteration of BAs, especially unconjugated BAs and secondary BAs, most likely through actions of gut microbiota. These alterations might confer potentially unfavorable impacts on colonic and host cardiometabolic health in healthy young adults. Clinical trial registry number: NCT02355795 listed on NIH website: ClinicalTrials.gov.

14.
Breast Cancer Res Treat ; 175(2): 353-368, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30830488

RESUMO

PURPOSE: Low expression of long intergenic non-coding RNA LINC00472 in breast cancer is associated with aggressive tumors and unfavorable disease outcomes in multiple clinical datasets, but the reasons for these associations were unknown. METHODS: To study the mechanisms underlying the lncRNA's connection to breast cancer, we investigated the molecular targets and regulation of LINC00472 in breast cancer cells, and analyzed relevant molecular features in relation to patient survival. Gene expression profiles of breast cancer cells overexpressing LINC00472 were analyzed for its regulatory pathways and downstream targets. Effects of LINC00472 overexpression on cell behaviors were evaluated in vitro and in vivo. Meta-analysis was performed using online datasets and our own study. RESULTS: Analysis of LINC00472 transcriptome revealed ERα upregulation of LINC00472 expression, and an ERα-binding site in the LINC00472 promoter was identified. Evaluation of LINC00472 overexpression also indicated a possible link between LINC00472 and NF-κB. Cell experiments confirmed that LINC00472 suppressed the phosphorylation of p65 and IκBα through binding to IKKß, inhibiting its phosphorylation. High LINC00472 expression inhibited tumor growth both in vitro and in vivo and suppressed aggressive tumor cell behaviors in vitro. Suppressing LINC00472 expression in ER-positive tumor cells increased cell aggressive behaviors. Tamoxifen treatment of ER-positive cells inhibited ERα and LINC00472 expression and increased p65 and IκBα phosphorylation. Meta-analysis showed that LINC00472 expression were higher in ER-positive than ER-negative tumors and that high expression was associated with better disease outcomes in ER-positive patients. CONCLUSIONS: The study demonstrates that ERα upregulates LINC00472 which suppresses the phosphorylation of NF-κB, and suggests that endocrine treatment may lower LINC00472 and increase NF-κB activities, leading to tumor progression and disease recurrence.


Assuntos
Neoplasias da Mama/genética , Receptor alfa de Estrogênio/genética , Recidiva Local de Neoplasia/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Células MCF-7 , Camundongos , Pessoa de Meia-Idade , NF-kappa B/genética , Recidiva Local de Neoplasia/patologia , Fosforilação/efeitos dos fármacos , Tamoxifeno/farmacologia , eIF-2 Quinase/genética
15.
Cancer Manag Res ; 11: 1465-1472, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863157

RESUMO

Purpose: This was a retrospective analysis of the impact of the expression of p53 in the dys-plastic surgical margins of early oral squamous cell carcinoma (OSCC) (pT1-2, N0). Patients and methods: Seventy-two patients with early oral squamous cell carcinoma (OSCC) were recruited. Margin characteristics were abstracted from the pathology report. Expression of p53 in dysplastic surgical margins was examined with the immunohistochemical method and was correlated with clinicopathological parameters and clinical outcomes. Results: Patients with moderate/severe dysplasia had poor local relapse-free survival (RFS) compared to those with mild dysplasia. Thirty-two (44.4%) had at least one p53-positive margin, and there was a significant association between the expression of p53 and tumor recurrence (P<0.001). p53-positive expression was correlated with RFS in patients with dysplastic margins, and its expression in moderate/severe dysplastic groups had a worse RFS than mild dysplastic groups. We also found that the grade of the dysplasia margin was not correlated with RFS in p53-negative groups. Multivariable analysis validated p53 expression in dysplastic surgical margins as an independent risk factor for recurrence. Conclusion: Our results validated that p53 expression was an independent risk factor for early OSCC with dysplastic surgical margins. Additional therapy and close follow-up are needed for these patients.

16.
Biomed Pharmacother ; 112: 108695, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30797154

RESUMO

To elucidate the potential function of lncRNA SNHG3 in the development of osteosarcoma. Quantitative real-time polymerase chain reaction was conducted for detection of SNHG3, miRNA-151a-3p and RAB22 A in osteosarcoma tissues and cells. Receiver operating characteristic curve was introduced to analyze the diagnostic potential of SNHG3 in osteosarcoma. Correlation between SNHG3 expression and the overall survival of osteosarcoma patients was evaluated using Kaplan-Meier method. Invasive and migratory potentials of osteosarcoma cells were examined by Transwell assay. Furthermore, dual-luciferase reporter gene assay, RNA-pull down and RIP assay were used to verify the binding of SNHG3/RAB22 A to miRNA-151a-3p. The function of SNHG3/miRNA-151a-3p/RAB22 A axis in osteosarcoma was finally confirmed by rescue experiments. SNHG3 and RAB22 A were highly expressed in osteosarcoma patients, while miRNA-151a-3p was lowly expressed. The overall survival of osteosarcoma patients with high expression of SNHG3 was shorter than those with low expression. SNHG3 overexpression markedly promoted invasive and migratory potentials of osteosarcoma cells. Through dual-luciferase reporter gene assay, both SNHG3 and RAB22 A could bind to miRNA-151a-3p. RAB22 A expression was positively regulated by SNHG3, but negatively regulated by miRNA-151a-3p. Finally, rescue experiments confirmed that RAB22 A overexpression could reverse the promotive effects of miRNA-151a-3p knockdown on invasive and migratory potentials of osteosarcoma cells. SNHG3 is highly expressed in osteosarcoma, and promotes the invasive and migratory potentials of osteosarcoma cells by absorbing miRNA-151a-3p to upregulate RAB22 A expression.


Assuntos
Movimento Celular/fisiologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , Osteossarcoma/metabolismo , RNA Longo não Codificante/biossíntese , Proteínas rab de Ligação ao GTP/biossíntese , Linhagem Celular Tumoral , Humanos , MicroRNAs/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/genética , Osteossarcoma/patologia , RNA Longo não Codificante/genética , Proteínas rab de Ligação ao GTP/genética
17.
J Biotechnol ; 292: 39-49, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30690095

RESUMO

Metal-driven papain-surfactant nanocomposite (PA@MSNC), a novel soft nanobiocatalyst, was successfully prepared via one-pot self-assembly technique in aqueous solution for the biosynthesis of N-(benzyloxycarbonyl)-L-alanyl-L-glutamine (Z-Ala-Gln) dipeptide in deep eutectic solvents (DESs). The metal-driven self-assembly process generated PA@MSNC as nanospheres of ˜130 nm in diameter, with high protein loading and relative enzyme activity of 420 mg/g and 80% (4270 U/g protein), respectively. PA@MSNC showed high apparent substrate affinity and catalytic efficiency. The stability of PA@MSNC at high temperature and extreme pH was significantly higher than that of free PA. Catalysis efficiency for the biosynthesis of Z-Ala-Gln by PA@MSNC in choline chloride: glycerol reaction medium was 1.69-fold higher than that of free PA, achieving a high product yield of 75.7% within 4 h. PA@MSNC also showed better techno-economic performance. We propose that enzyme-surfactant nanocomposite via metal-driven dynamically reversible coordination interactions contribute simultaneously promotes catalytic flexibility and configurational stability. The generated PA@MSNC has potential practical implications for green synthesis of dipeptide in DESs.


Assuntos
Ácido Desoxicólico/química , Dipeptídeos/química , Manganês/química , Nanocompostos/química , Papaína/química , Tensoativos/química , Biocatálise , Colina/química , Glicerol/química , Concentração de Íons de Hidrogênio , Solventes/química , Temperatura Ambiente
18.
Drug Metab Dispos ; 47(3): 283-294, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606729

RESUMO

The gut microbiota modifies endogenous primary bile acids (BAs) to produce exogenous secondary BAs, which may be further metabolized by cytochrome P450 enzymes (P450s). Our primary aim was to examine how the host adapts to the stress of microbe-derived secondary BAs by P450-mediated oxidative modifications on the steroid nucleus. Five unconjugated tri-hydroxyl BAs that were structurally and/or biologically associated with deoxycholate (DCA) were determined in human biologic samples by liquid chromatography-tandem mass spectrometry in combination with enzyme-digestion techniques. They were identified as DCA-19-ol, DCA-6ß-ol, DCA-5ß-ol, DCA-6α-ol, DCA-1ß-ol, and DCA-4ß-ol based on matching in-laboratory synthesized standards. Metabolic inhibition assays in human liver microsomes and recombinant P450 assays revealed that CYP3A4 and CYP3A7 were responsible for the regioselective oxidations of both DCA and its conjugated forms, glycodeoxycholate (GDCA) and taurodeoxycholate (TDCA). The modification of secondary BAs to tertiary BAs defines a host liver (primary BAs)-gut microbiota (secondary BAs)-host liver (tertiary BAs) axis. The regioselective oxidations of DCA, GDCA, and TDCA by CYP3A4 and CYP3A7 may help eliminate host-toxic DCA species. The 19- and 4ß-hydroxylation of DCA species demonstrated outstanding CYP3A7 selectivity and may be useful as indicators of CYP3A7 activity.


Assuntos
Citocromo P-450 CYP3A/metabolismo , Ácido Desoxicólico/metabolismo , Microbioma Gastrointestinal/fisiologia , Adulto , Ácido Desoxicólico/sangue , Ácido Desoxicólico/toxicidade , Ácido Desoxicólico/urina , Feminino , Voluntários Saudáveis , Humanos , Hidroxilação , Fígado/metabolismo , Masculino , Microssomos Hepáticos , Oxirredução , Adulto Jovem
19.
ACS Sens ; 4(1): 20-25, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30525479

RESUMO

Bioluminescent sensor proteins provide attractive tools for applications ranging from in vivo imaging to point-of-care testing. Here we introduce a new class of ratiometric bioluminescent sensor proteins that do not rely on direct modulation of BRET efficiency, but are based on competitive intramolecular complementation of split NanoLuc luciferase. Proof of concept for the feasibility of this sensor principle was provided by developing a blue-red light emitting sensor protein for the detection of anti-HIV1-p17 antibodies with a 500% change in emission ratio and a Kd of 10 pM. The new sensor design also improved the dynamic response of a sensor for the therapeutic antibody cetuximab 4-fold, allowing the direct quantification of this anti-EGFR antibody in undiluted blood plasma. The modular sensor architecture allows easy and systematic tuning of a sensor's dynamic range and should be generally applicable to allow rational engineering of bioluminescent sensor proteins.


Assuntos
Anticorpos Anti-HIV/sangue , Luciferases/química , Proteínas Luminescentes/química , Técnicas de Transferência de Energia por Ressonância de Bioluminescência/métodos , Cetuximab/imunologia , Corantes Fluorescentes/química , Anticorpos Anti-HIV/imunologia , Proteínas Luminescentes/imunologia , Estudo de Prova de Conceito
20.
Gene ; 686: 194-202, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30340050

RESUMO

Previous studies have proposed that caloric restriction (CR) regulates many cell functions and prolongs the lifespan of an organism. Our previous studies proposed that CR also prevents follicular activation and preserves the ovarian reserve in mice by activating SIRT1. To test if SIRT1 preserves the ovarian reserve and prolongs the ovarian longevity, we generated SIRT1 knock-in mice that can overexpress SIRT1 in oocytes of the mouse. Ovaries of the mice at ages 35 days and 15 months were collected, and the follicular development and follicular reserve were examined. The vaginal opening and onset of estrus of transgenic female mice (both the homozygous and heterozygous for SIRT1 overexpression) were later than that of wild-type mice. Both the homozygous and heterozygous SIRT1-overexpressing mice had a larger and stronger reproductive capacity than wild-type mice. Moreover, 35-day-old and 15-month-old homozygous and heterozygous SIRT1-overexpressing mice also had a higher mean number and percentage of healthy follicles, fewer atretic follicles than wild-type mice, and the mean number and percentage of primordial follicles in both the homozygous and heterozygous SIRT1-overexpressing mice were higher than wild-type mice at the same age. However, the phenotypes of heterozygous and homozygous transgenic mice came no difference. Immunohistochemistry showed increased expression of SIRT1 and FOXO3a, and decreased expression of mTOR in both the homozygous and heterozygous SIRT1-overexpressing mice compared with wild-type mice. Thus, oocyte-specific SIRT1-overexpressing mice continuously activate FOXO3a and suppress mTOR and have a larger reproductive capacity, larger follicle reserve and longer ovarian lifespan.


Assuntos
Restrição Calórica , Regulação Enzimológica da Expressão Gênica , Reserva Ovariana , Ovário/enzimologia , Sirtuína 1 , Animais , Feminino , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Técnicas de Introdução de Genes , Camundongos , Camundongos Transgênicos , Ovário/citologia , Sirtuína 1/biossíntese , Sirtuína 1/genética , Serina-Treonina Quinases TOR/biossíntese , Serina-Treonina Quinases TOR/genética
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