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1.
Mol Ther ; 31(1): 260-268, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36245127

RESUMO

Accurate genome editing based on various molecular tools has always been the focus of gene-editing research and the primary goal for therapeutic application. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system is a well-established gene-editing method that is preferred due to its simplicity and high efficiency. In this study, a group of single-stranded DNA aptamers with high affinity and high specificity for the Cas9 protein were obtained by the systematic evolution of ligands through the exponential enrichment method. Their binding affinity and possible binding domains to the Cas9 protein were analyzed. In addition, we demonstrated the effectiveness of aptamers in regulating dCas9-modulated gene transcription, in terms of both transcriptional activation and repression. Additionally, the aptamers successfully reduced the off-target effect and improved the efficiency of gene homologous recombination repair mediated by CRISPR-Cas9. The findings suggest a potential method to better control precise gene editing and enrich the diversity of modulating tools for the CRISPR-Cas9 system.


Assuntos
Aptâmeros de Nucleotídeos , Proteína 9 Associada à CRISPR , Proteína 9 Associada à CRISPR/genética , Reparo de DNA por Recombinação , Sistemas CRISPR-Cas , Aptâmeros de Nucleotídeos/genética , Clivagem do DNA , Edição de Genes/métodos
2.
Angew Chem Int Ed Engl ; 63(30): e202405678, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38739309

RESUMO

Cyclobutanes are popular structural units in bioactive compounds and versatile intermediates in synthetic chemistry, but their synthesis is challenging owing to high ring strain. In this study, a novel method for highly regio- and diastereoselective synthesis of fluoroalkylcyclobutanes bearing vicinal quaternary and tertiary stereocenters is realized by a photocatalytic 4-exo-trig cyclization cascade of thioalkynes or trifluoromethylalkenes. Density functional theory calculations reveal that a unique fluorine effect, arising from hyperconjugative π→σ*C-F interactions, accounts for the regio-reversed radical addition at the sterically hindered alkene carbon, which facilitates an unprecedented 4-exo-trig ring closure. This chemistry enables the direct and controllable construction of medicinally valuable quaternary-carbon-containing cyclobutanes from readily available raw materials, nicely complementing the existing methods.

3.
J Transl Med ; 21(1): 56, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717944

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a major worldwide health problem due to its high prevalence and mortality rate. A disintegrin and metalloproteinase 12 (ADAM12) is aberrantly expressed in various cancers and plays an important role in tumor progression. However, its explicit effect and molecular mechanism in ccRCC remain unclear. METHODS: We investigated the dysregulation of ADAM12 in ccRCC through public databases and bioinformatics analyses. The expression of ADAM12 was further verified in ccRCC tissues by RT-qPCR and immunohistochemistry (IHC). The relationship between ADAM12 expression and clinicopathological characteristics was analyzed statistically. The effects of ADAM12 on the proliferation, migration and invasion of ccRCC cells were examined by in vitro and in vivo experiments. RESULTS: ADAM12 was significantly upregulated in ccRCC tissues and associated with poor prognosis in ccRCC patients. ADAM12 promoted ccRCC cell proliferation, migration and invasion in vitro and the growth of subcutaneous tumors in vivo. Knockdown of ADAM12 successfully suppressed its oncogenic function. Mechanistically, its overexpression induced epithelial-mesenchymal transition (EMT) by downregulating E-cadherin and upregulating N-cadherin and Snail. Moreover, ADAM12 participated in the epidermal growth factor receptor (EGFR) pathway and activated the downstream signal ERK1/2 by shedding the EGFR ligand, thereby upregulating target genes including c-Myc, enhancing cell survival and invasion ability, and promoting tumor progression, metastasis and the induction of EMT. CONCLUSIONS: High expression of ADAM12 induced EMT and promoted cell proliferation, migration, and invasion by activating the EGFR/ERK signaling pathway in ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Transdução de Sinais/genética , Proliferação de Células/genética , Neoplasias Renais/patologia , Receptores ErbB/metabolismo , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteína ADAM12/genética , Proteína ADAM12/metabolismo
4.
Analyst ; 148(20): 4939-4953, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37721109

RESUMO

Genetically encoded biosensors based on fluorescent proteins (FPs) are powerful tools for tracking analytes and cellular events with high spatial and temporal resolution in living cells and organisms. Compared with intensiometric readout and ratiometric readout, fluorescence lifetime readout provides absolute measurements, independent of the biosensor expression level and instruments. Thus, genetically encoded fluorescence lifetime biosensors play a vital role in facilitating accurate quantitative assessments within intricate biological systems. In this review, we first provide a concise description of the categorization and working mechanism of genetically encoded fluorescence lifetime biosensors. Subsequently, we elaborate on the combination of the fluorescence lifetime imaging technique and lifetime analysis methods with fluorescence lifetime biosensors, followed by their application in monitoring the dynamics of environment parameters, analytes and cellular events. Finally, we discuss worthwhile considerations for the design, optimization and development of fluorescence lifetime-based biosensors from three representative cases.

5.
BMC Urol ; 23(1): 104, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280589

RESUMO

BACKGROUND: Metabolism is a hallmark of cancer and it involves in resistance to antitumor treatment. Therefore, the purposes of this study are to classify metabolism-related molecular pattern and to explore the molecular and tumor microenvironment characteristics for prognosis predicting in prostate cancer. METHODS: The mRNA expression profiles and the corresponding clinical information for prostate cancer patients from TCGA, cBioPortal, and GEO databases. Samples were classified using unsupervised non-negative matrix factorization (NMF) clustering based on differentially expressed metabolism-related genes (MAGs). The characteristics of disease-free survival (DFS), clinicopathological characteristics, pathways, TME, immune cell infiltration, response to immunotherapy, and sensitivity to chemotherapy between subclusters were explored. A prognostic signature was constructed by LASSO cox regression analysis based on differentially expressed MAGs and followed by the development for prognostic prediction. RESULTS: A total of 76 MAGs between prostate cancer samples and non-tumorous samples were found, then 489 patients were divided into two metabolism-related subclusters for prostate cancer. The significant differences in clinical characteristics (age, T/N stage, Gleason) and DFS between two subclusters. Cluster 1 was associated with cell cycle and metabolism-related pathways, and epithelial-mesenchymal transition (EMT), etc., involved in cluster 2. Moreover, lower ESTIMATE/immune/stromal scores, lower expression of HLAs and immune checkpoint-related genes, and lower half-maximal inhibitory concentration (IC50) values in cluster 1 compared with cluster 2. The 10 MAG signature was identified and constructed a risk model for DFS predicting. The patients with high-risk scores showed poorer DFS. The area under the curve (AUC) values for 1-, 3-, 5-year DFS were 0.744, 0.731, 0.735 in TCGA-PRAD dataset, and 0.668, 0.712, 0.809 in GSE70768 dataset, 0.763, 0.802, 0.772 in GSE70769 dataset. Besides, risk score and Gleason score were identified as independent factors for DFS predicting, and the AUC values of risk score and Gleason score were respectively 0.743 and 0.738. The nomogram showed a favorable performance in DFS predicting. CONCLUSION: Our data identified two metabolism-related molecular subclusters for prostate cancer that were distinctly characterized in prostate cancer. Metabolism-related risk profiles were also constructed for prognostic prediction.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/genética , Intervalo Livre de Doença , Intervalo Livre de Progressão , Algoritmos , Ciclo Celular , Prognóstico , Microambiente Tumoral
6.
Mikrochim Acta ; 190(6): 225, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37195510

RESUMO

A two-photon excited ratiometric fluorescent pH sensor is reported by combining L-cysteine-protected AuNCs (Cys@AuNCs) with fluorescein isothiocyanate (FITC). Cys@AuNCs were synthesized through a one-step self-reduction route and showed pH-responsive photoluminescence at 650 nm. Benefiting from the opposite pH response of Cys@AuNCs and FITC, the fluorescence ratio (F515 nm/F650 nm) of FITC&Cys@AuNCs provided a large dynamic range of 200-fold for pH measurement in the response interval of pH 5.0-8.0. Based on the excellent two-photon absorption coefficient of Cys@AuNCs, the sensor was expected to achieve sensitive quantitation of pH in living cells under two-photon excitation. In addition, colorimetric biosensing based on enzyme-like metal nanoclusters has attracted wide attention due to their low-cost, simplicity, and practicality. It is crucial to develop high catalytic activity nanozyme from the viewpoint of practical application. The synthesized Cys@AuNCs exhibited excellent photoactivated peroxidase-like activity with high substrate affinity and catalytic reaction rate, promising for rapid colorimetric biosensing of field analysis and the control of catalytic reactions by photostimulation.


Assuntos
Nanopartículas Metálicas , Peroxidase , Fluoresceína-5-Isotiocianato , Ouro , Peroxidases , Corantes Fluorescentes , Concentração de Íons de Hidrogênio
7.
Molecules ; 28(14)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37513333

RESUMO

The choline prolinate ([Ch][Pro]) as a hydrogen bond acceptor and ethylene glycol (EG) as a hydrogen bond donor are both used to synthesize the deep eutectic solvents (DESs) [Ch][Pro]-EG to capture CO2. The CO2 capacity of [Ch][Pro]-EG is determined, and the nuclear magnetic resonance (NMR) and infrared (IR) spectrum are used to investigate the CO2 capture mechanism. The results indicate that CO2 reacts with both the amino group of [Pro]- anion and the hydroxyl group of EG, and the mechanism found in this work is different from that reported in the literature for the [Ch][Pro]-EG DESs.

8.
Int Braz J Urol ; 49(3): 281-298, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37115175

RESUMO

BACKGROUND: Several studies have explored the impact of BMI on size and composition of urinary stones. Because there were controversies, a meta-analysis was necessary to be carried out to provide some evidence of the relationship of BMI and urolithiasis. MATERIALS AND METHODS: PubMed, Medline, Embase, Web of Science databases, and the Cochrane Library were searched up to August 12th 2022 for eligible studies. The urolithiasis patients were summarized into two groups: BMI < 25 and ≥ 25 kg/m2. Summary weighted mean difference (WMD), relative risk (RR) and 95% confidence intervals (CI) were calculated through random effects models in RevMan 5.4 software. RESULTS: A total of fifteen studies involving 13,233 patients were enrolled in this meta-analysis. There was no significant correlation of BMI and size of urinary stone (WMD -0.13mm, 95% CI [-0.98, 0.73], p = 0.77). Overweight and obesity increased the risk of uric acid stones in both genders and in different regions (RR=0.87, [95% CI] = 0.83, 0.91, p<0.00001). There was a higher risk of calcium oxalate stones formation in overweight and obesity group in total patients (RR=0.95, [95% CI] = 0.91, 0.98, p = 0.006). The relationship of BMI and calcium phosphate was not observed in this meta-analysis (RR=1.12, [95% CI] = 0.98, 1.26, p = 0.09). Sensitivity analysis was performed and indicated similar results. CONCLUSIONS: The current evidence suggests a positive association between BMI and uric acid and calcium oxalate stones. It would be of great guiding significance to consider losing weight when treating and preventing urinary stones.


Assuntos
Cálculos Urinários , Urolitíase , Humanos , Feminino , Masculino , Índice de Massa Corporal , Sobrepeso/complicações , Oxalato de Cálcio , Ácido Úrico , Urolitíase/etiologia , Obesidade/complicações
9.
Biochem Biophys Res Commun ; 623: 81-88, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35878427

RESUMO

The transcription factor HOXB13 is bound up with the occurrence, progression and drug fast of many kinds of cancer. Nevertheless, the specific molecular mechanism of HOXB13 in hepatocellular carcinoma (HCC) is still unknown. This provides an obstacle to the exploration of HCC treatments targeting HOXB13. This study found that HOXB13 was up-regulated in HCC tissues. HOXB13 enhanced the multiplication and metastasis of HCC cells. It enhanced HCC cell drug and anoikis resistance. The analysis of HCC RNA seq data indicated that the expression of HOXB13 and PIMREG were positively correlated. Luciferase report assay showed that HOXB13 could activate PIMREG promoter transcription. The results of RT-qPCR and western blot showed that HOXB13 regulated the transcription of PIMREG. Western blot proved that high expression of PIMREG participated in DNA damage repair and cell cycle regulation by up-regulating RAD51, BRCA1, CDC25A, CDC25B and CDC25C and down-regulating HIPK2. This led to a significant increase in DNA repair capacity, accelerated cell cycle progression, and insensitive to DNA damage. Down-regulation of PIMREG in Hep3B cells overexpressing HOXB13 attenuated the phenotype induced by HOXB13. Therefore, HOXB13 functioned through PIMREG instead of directly regulating the transcription of RAD51, BRCA1, CDC25A, CDC25B and CDC25C. The same results were obtained in vivo. It was concluded that HOXB13 affected the expression of cell cycle and DNA repair related factors by up-regulating the transcription of PIMREG, thereby promoting the progression of HCC and enhancing the resistance of HCC to chemotherapeutics.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Resistência a Medicamentos , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Hepáticas/patologia , Proteínas Nucleares , Proteínas Serina-Treonina Quinases , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
BMC Cancer ; 20(1): 1059, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33143662

RESUMO

Zoledronic acid (ZA) is one of the most important and effective class of anti-resorptive drug available among bisphosphonate (BP), which could effectively reduce the risk of skeletal-related events, and lead to a treatment paradigm for patients with skeletal involvement from advanced cancers. However, the exact molecular mechanisms of its anticancer effects have only recently been identified. In this review, we elaborate the detail mechanisms of ZA through inhibiting osteoclasts and cancer cells, which include the inhibition of differentiation of osteoclasts via suppressing receptor activator of nuclear factor κB ligand (RANKL)/receptor activator of nuclear factor κB (RANK) pathway, non-canonical Wnt/Ca2+/calmodulin dependent protein kinase II (CaMKII) pathway, and preventing of macrophage differentiation into osteoclasts, in addition, induction of apoptosis of osteoclasts through inhibiting farnesyl pyrophosphate synthase (FPPS)-mediated mevalonate pathway, and activation of reactive oxygen species (ROS)-induced pathway. Furthermore, ZA also inhibits cancer cells proliferation, viability, motility, invasion and angiogenesis; induces cancer cell apoptosis; reverts chemoresistance and stimulates immune response; and acts in synergy with other anti-cancer drugs. In addition, some new ways for delivering ZA against cancer is introduced. We hope this review will provide more information in support of future studies of ZA in the treatment of cancers and bone cancer metastasis.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Osteoclastos/citologia , Ácido Zoledrônico/farmacologia , Animais , Neoplasias Ósseas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ácido Zoledrônico/uso terapêutico
11.
Med Sci Monit ; 26: e919888, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32210223

RESUMO

BACKGROUND This retrospective study aimed to investigate the risk factors associated with the recurrence of L5-S1 disc herniation after percutaneous endoscopic transforaminal discectomy (PETD). MATERIAL AND METHODS There were 484 patients L5-S1 disc herniation who underwent PETD who were divided into the recurrence group (n=46) and the non-recurrence group (n=438). Transforaminal endoscopic approaches included modifications of the Yeung endoscopy spine system (YESS) (the intraforaminal intradiscal approach) and the transforaminal endoscopic spine system (TESSYS) (intraforaminal extradiscal approach). Demographic and clinical characteristics and imaging data were analyzed. The two study groups were compared to determine the factors associated with the recurrence of L5-S1 disc herniation. The patients underwent postoperative follow-up for between one and four years. RESULTS At follow-up, 9.504% of patients (46/484) with the recurrence of L5-S1 disc herniation following PETD when compared with the non-recurrence group showed no significant difference for time to return to work, gender, history of diabetes mellitus, trauma, duration of symptoms, smoking and alcohol history, hypertension, location of disc herniation, transverse process length, intervertebral space height, and pelvic incidence angle (P>0.05). However, age, body mass index (BMI), the degree of disc degeneration, sagittal range of motion, lumbar lordosis angle, and sacral slope were significantly associated with the recurrence of L5-S1 disc herniation following PETD (P<0.05). Logistic regression analysis supported these main associations. CONCLUSIONS The recurrence of L5-S1 disc herniation following PETD was significantly associated with increased age and BMI, more severe disc degeneration, increased sagittal range of motion, increased lumbar lordosis, and sacral slope.


Assuntos
Discotomia Percutânea , Endoscopia , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Sacro/cirurgia , Índice de Massa Corporal , Feminino , Humanos , Ílio/diagnóstico por imagem , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/fisiopatologia , Modelos Logísticos , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pelve/cirurgia , Amplitude de Movimento Articular , Recidiva , Estudos Retrospectivos , Fatores de Risco
12.
Ecotoxicol Environ Saf ; 170: 763-770, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30583287

RESUMO

Groundwater contaminated by Cr(VI) requires effective remediation to prevent adverse environmental impacts. The biodegradation of Cr(VI) has been documented for several decades, but little remains known about the removal fate of chromium, including the main species of reductase (sites) and functional genes involved in Cr(VI) reduction in mixed bacterial consortium. Cr(VI) reduction in this study was verified to be an enzyme-mediated process. Meanwhile, Cr(VI) reduction of different cell components demonstrated that the extracellular enzyme was the main active substance, and the distribution of Cr after experiment was quantified using mass balance calculation. Furthermore, the optimal pH for reduction was 8.0, with the reduction rate decreasing with increasing initial Cr(VI) concentrations. The co-existing oxyanions had little effect on Cr(VI) reduction, while the presence of other heavy metals had a relatively significant influence. The evolutionary behavior of microbial community structure and functional genes affected by Cr(VI) were also analyzed, which provided new insights on the underlying mechanisms involved in bioreduction in this study. These results generated new understanding of the reduction mechanisms on the Cr-relevant bacterial species and genes, which would be helpful in designing strategies for the bioremediation of Cr(VI) contaminated water.


Assuntos
Bactérias/enzimologia , Bactérias/genética , Cromo/metabolismo , Ânions/química , Biodegradação Ambiental , Cromo/química , Água Subterrânea/microbiologia , Concentração de Íons de Hidrogênio , Microbiota , Oxirredução
14.
World J Surg Oncol ; 16(1): 138, 2018 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30001205

RESUMO

BACKGROUND: Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values as imaging biomarkers of rectal cancer are currently a hot research spot. The use of ADC values for preoperative judgment of pathological features in rectal cancer has been generally accepted. The image quality evaluation of conventional diffusion is severe deformation, and the measurement of ADC values can easily lead to bias. Readout-segmented echo-planar diffusion-weighted imaging (RESOLVE) provides high signal-to-noise ratio images and significantly reduces distortions caused by magnetosensitive effects. The purpose of this study was to explore the correlations between ADC values of RESOLVE and pathological prognostic factors in rectal adenocarcinoma. METHODS: We collected pathological data of 89 patients with pathologically confirmed rectal adenocarcinoma who directly underwent surgical resection without receiving adjuvant therapy. The patients were grouped according to the pathologic type, gross classification, degree of differentiation, TN stage, and immunohistochemical expression of epidermal growth factor receptor (EGFR). RESULTS: RESOLVE ADC values of rectal cancer were measured at b = 800, and correlations between the RESOLVE ADC values obtained in different groups were analysed. We found that RESOLVE ADC values in the ulcer-type group were significantly higher than those in the eminence-type group. CONCLUSION: RESOLVE ADC values in different pathologic types of rectal cancer were significantly different. RESOLVE ADC values in the EGFR-positive group were significantly lower than those in the EGFR-negative group. There was no significant difference in RESOLVE ADC values between different degrees of pathologic differentiation, TN stages, and positive or negative lymph nodes. The quantitative description of RESOLVE ADC values could be used to assess the biological behaviour of rectal adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Neoplasias Retais/diagnóstico por imagem , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Receptores ErbB/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retais/metabolismo , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos
15.
Eur J Nutr ; 56(3): 1169-1177, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26873099

RESUMO

PURPOSE: The association between dietary carbohydrate intake, glycemic index (GI) and glycemic load (GL), and risk of gastric cancer (GC) has been investigated by many studies. However, the results of these studies were controversial. The aim of our study was to systematically assess this issue. METHODS: PUBMED and EMBASE were searched up to March 2015, and either a fixed- or a random-effects model was adopted to estimate overall relative risks (RRs). Dose-response, meta-regression, subgroup, and publication bias analyses were applied. RESULTS: Twenty-six studies with approximately 540,000 participants were finally included in this meta-analysis. High level of dietary carbohydrate intake (pooled RR 1.17, 95 % CI 0.91-1.50), GI (pooled RR 1.17, 95 % CI 0.80-1.69), and GL (pooled RR 1.06, 95 % CI 0.90-1.26) were all nonsignificantly associated with incidence of GC. In addition, no significant dose-response relationship was observed between carbohydrate intake, GI and GL, and the risk of GC. However, further subgroup analyses based on gender and geographic region suggested a significant association between higher carbohydrate intake (pooled RR 1.52, 95 % CI 1.10-2.08), GL (pooled RR 1.41, 95 % CI 1.04-1.92), and GC risk in males subgroup, and between higher carbohydrate intake (pooled RR 1.69, 95 % CI 1.36-2.09) and GC risk in Asian studies. CONCLUSIONS: No significant association was found between dietary carbohydrate intake, GI and GL, and risk of GC. However, significantly positive association was observed in the males subgroup and Asian studies.


Assuntos
Carboidratos da Dieta/administração & dosagem , Índice Glicêmico , Carga Glicêmica , Neoplasias Gástricas/epidemiologia , Glicemia/metabolismo , Bases de Dados Factuais , Humanos , Incidência , Fatores de Risco
16.
Tumour Biol ; 37(1): 897-903, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26254614

RESUMO

Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) was identified to be the first long non-coding RNA as a biomarker of independent prognostic value for early stage non-small cell lung cancer patient survival. In recent years, the association between upregulated tissue MALAT1 level and incidence of various cancers including bladder cancer, colorectal cancer, and renal cancer has been widely discussed. The aim of our present study was to assess the potential prognostic value of MALAT1 in various human cancers. PubMed, Embase, Ovid, and Cochrane Library databases were systematically searched, and eligible studies evaluating the prognostic value of MALAT1 in various cancers were included. Finally, 11 studies encompassing 1216 participants reporting with sufficient data were enrolled in the current meta-analysis. The pooled hazard ratio (HR) was 2.05 (95 % confidence interval (CI) 1.64-2.55, p < 0.01) for overall survival (OS) and 2.66 (95 % CI 1.86-3.80, p < 0.01) for disease-free survival (DFS). In conclusion, high tissue MALAT1 level was associated with an inferior clinical outcome in various cancers, suggesting that MALAT1 might serve as a potential prognostic biomarker for various cancers.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias/diagnóstico , Neoplasias/metabolismo , RNA Longo não Codificante/metabolismo , Biomarcadores Tumorais/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Neoplasias/genética , Neoplasias/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Resultado do Tratamento
17.
Gut ; 64(9): 1419-25, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25239119

RESUMO

OBJECTIVE: The objective of this meta-analysis was to systematically assess the survival benefit of aspirin use before or after diagnosis for patients with colorectal cancer (CRC). DESIGN: Relevant studies were identified through searching PubMed, Embase and Cochrane databases before May 2014. Two investigators extracted data independently for baseline characteristics and outcomes from the included studies. Either a fixed-effects or a random-effects model was derived to composite the pooled HR for overall mortality and CRC-specific mortality of CRC. RESULTS: Seven studies on postdiagnosis aspirin therapy and seven studies on prediagnosis aspirin use were finally included in this meta-analysis. The overall survival benefit associated with postdiagnosis aspirin use represented an HR of 0.84 (95% CI 0.75 to 0.94). This effect was observed both in colon cancer (HR=0.78, 95% CI 0.64 to 0.96) and in rectal cancer (HR=0.90, 95% CI 0.83 to 0.98). Besides, the survival benefit of postdiagnosis aspirin use appeared to be confined to those patients with positive prostaglandin endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase-2, COX-2) expression (HR=0.65, 95% CI 0.50 to 0.85) and with mutated PIK3CA tumours (HR=0.58, 95% CI 0.37 to 0.90). Aspirin use postdiagnosis was not associated with CRC-specific mortality (HR=0.77, 95% CI 0.52 to 1.14). We observed no evidence of an association between prediagnosis aspirin use and CRC overall mortality (HR=1.01, 95% CI 0.96 to 1.06) or CRC-specific mortality (HR=0.93, 95% CI 0.82 to 1.05). CONCLUSIONS: These findings provide further indication that postdiagnosis aspirin therapy improved CRC overall survival, especially for patients with positive PTGS2 (COX-2) expression and mutated PIK3CA tumours.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/prevenção & controle , Causas de Morte , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Ciclo-Oxigenase 2/genética , Esquema de Medicação , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Mutação , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Análise de Sobrevida
18.
Am J Cancer Res ; 14(5): 2202-2215, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859860

RESUMO

Bladder cancer stands as one of the prevalent malignancies in urological clinics, highlighting the pressing need to uncover prognostic or therapeutic avenues. ITM2A, a transmembrane protein, has been identified as a suppressor in tumor progression recently. Our study underscored a significant correlation between low ITM2A expression in bladder cancer tissues and high tumor grade, AJCC stage, and poor overall survival time. Additionally, our findings demonstrated that reinstating ITM2A expression impeded cell proliferation, migration, and invasion, while conversely, its suppression enhanced these malignant behaviors. Furthermore, we elucidated that ITM2A could suppress malignant phenotypes of bladder cancer cells via inhibiting activation of the STAT3 induced by IL-6. In conclusion, our research unveiled the mechanistic role of ITM2A in inhibiting tumor progression, shedding light on its potential as a prognostic predictor and therapeutic target in bladder cancer management.

19.
RSC Adv ; 14(8): 5479-5491, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38352683

RESUMO

A method for synthesizing carbon spheres with a tunable particle size and internal structure from polyfurfuryl alcohol (PFA) was developed. By tuning the concentration of a structure directing agent (polypropylene glycol, PPG), we found a mechanism to tune the inner architecture of carbon spheres driven by water-solubility. A mixture of PFA and PPG transferred from the "water-in-oil" phase to an "oil-in-water" phase with an increasing content of PPG because of a difference in water-solubility between furfuryl alcohol (FA), PFA, and PPG. As a result, the internal morphology of the carbon sphere evolved from a "cheese-like" to a "pomegranate-like" structure, which was accompanied by an increasing specific surface area and pore volume. Furthermore, the separation of C2H2 and C2H3Cl was tested on the 25%-FACS (furfuryl alcohol-based carbon sphere) sample under different activation treatments with CO2 or CO2-NH3, with the coexisting "cheese-like" and "pomegranate-like" inner structures, owing to its moderate pore volume and mechanical strength. The maximum adsorption capacity of C2H3Cl reached 0.77 mmol g-1, while C2H2 was adsorbed in significantly lower quantities. It is believed that the high polarizability and high dipole moment of the C2H3Cl molecule primarily contribute to the excellent performance of C2H2 and C2H3Cl separation, and the introduction of polar N-containing groups on the carbon skeleton further promotes C2H3Cl adsorption.

20.
J Thorac Dis ; 16(2): 1021-1033, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38505038

RESUMO

Background: Non-small cell lung cancer (NSCLC) patients with extrathoracic metastasis (EM) are a highly heterogeneous cohort. Some of these patients could benefit from primary tumor surgery. This study aimed to identify potential NSCLC patients with EM suitable for primary tumor resection and to determine the optimal therapeutic strategy. Methods: NSCLC patients with EM were extracted from the Surveillance, Epidemiology and End Results database between 2010 and 2015. They were stratified into subgroups with single and multi-EMs. Cox regression analysis was adopted to identify prognostic factors for overall survival (OS). The Kaplan-Meier method was used to compare the OS among patients who received different treatment modalities. Results: The univariate Cox regression analysis demonstrated that advanced age, male sex, race (black), married status, squamous cell carcinoma, higher histological grade, advanced T or N stage, contralateral lung metastasis, multi-EMs, tumor size >2 cm, and lack of treatment were associated with poorer OS in patients with NSCLC (P<0.05). Multivariate Cox regression analysis revealed that the number of EM and treatment modalities were independent prognostic factors affecting OS (P<0.001). For patients with single EM, those who did not receive treatment and those who underwent single-agent chemotherapy, single-agent surgery, surgery combined with chemotherapy, surgery combined with radiotherapy, or surgery combined with chemoradiotherapy had median OS times of 3.0, 11.0, 12.0, 26.0, 11.0, and 25.0 months, respectively. Compared to monotherapy, combination therapy showed significant benefits for patients with single EM in NSCLC. Furthermore, patients with single EM who underwent lobectomy, bilobectomy, or pneumonectomy had significantly longer survival than those who underwent sublobar resection, even when the primary tumor size was ≤2 cm (P=0.04). Conclusions: Primary tumor surgery could benefit NSCLC patients with single EM; lobectomy was at least warranted to improve survival even for primary tumors with size ≤2 cm.

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