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1.
J Cell Mol Med ; 28(1): e18041, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37987202

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is difficult to treat due to the high recurrence rate and therapy intolerance, so finding potential therapeutic targets for DLBCL is critical. FK506-binding protein 3 (FKBP3) contributes to the progression of various cancers and is highly expressed in DLBCL, but the role of FKBP3 in DLBCL and its mechanism are not clear. Our study demonstrated that FKBP3 aggravated the proliferation and stemness of DLBCL cells, and tumour growth in a xenograft mouse model. The interaction between FKBP3 and parkinsonism associated deglycase (PARK7) in DB cells was found using co-immunoprecipitation assay. Knockdown of FKBP3 enhanced the degradation of PARK7 through increasing its ubiquitination modification. Forkhead Box O3 (FOXO3) belongs to the forkhead family of transcription factors and inhibits DLBCL, but the underlying mechanism has not been reported. We found that FOXO3 bound the promoter of FKBP3 and then suppressed its transcription, eventually weakening DLBCL. Mechanically, FKBP3 activated Wnt/ß-catenin signalling pathway mediated by PARK7. Together, FKBP3 increased PARK7 and then facilitated the malignant phenotype of DLBCL through activating Wnt/ß-catenin pathway. These results indicated that FKBP3 might be a potential therapeutic target for the treatment of DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B , beta Catenina , Humanos , Camundongos , Animais , beta Catenina/metabolismo , Proteína Desglicase DJ-1/genética , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Wnt/genética , Fenótipo , Linfoma Difuso de Grandes Células B/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a Tacrolimo/metabolismo
2.
Analyst ; 149(10): 2796-2800, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38669149

RESUMO

A near-infrared fluorescent nanoprobe consisting of Nile blue-capped ZIF-90 is first proposed for real-time imaging of mitochondrial ATP. Owing to the strong binding of ATP with Zn2+, the structure of the probe is disrupted, leading to the release of fluorescent NB.


Assuntos
Trifosfato de Adenosina , Corantes Fluorescentes , Mitocôndrias , Oxazinas , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Oxazinas/química , Humanos , Mitocôndrias/química , Mitocôndrias/metabolismo , Trifosfato de Adenosina/análise , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Células HeLa , Raios Infravermelhos , Imagem Óptica/métodos , Nanopartículas/química
3.
Environ Res ; 252(Pt 3): 119016, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677405

RESUMO

Household garbage rooms release abundant bioaerosols and are an important source of pathogens; however, information on the distribution and survival patterns of pathogens in different waste components is limited. In this study, a culture method and 16S rRNA high-throughput sequencing were used to determine bacterial communities, culturable pathogens, and human bacterial pathogens (HBPs). The results showed that abundant culturable bacteria were detected in all waste types, and a large number of S. aureus was detected on the surface of recyclable wastes, whereas S. aureus, total coliforms, Salmonella, Enterococcus, and hemolytic bacteria were detected in food waste and other waste. The activities of these detected pathogenic bacteria decreased after 24 h of storage but re-activated within one week. Factors affecting the emergence of pathogens varied with different waste components. Sequencing results showed that Pseudomonas, Acinetobacter, and Burkholderia were abundant in the waste samples, whereas Achromobacter, Exiguobacteriums, Bordetella, and Corynebacterium were the primary pathogens in the bioaerosol and wall attachment. The results of traceability analysis showed that bioaerosol microbes were mainly derived from raw kitchen waste (5.98%) and plastic and paper contaminated with food waste (19.93%) in garbage rooms. In addition, bioaerosols were the main source of microflora in the wall attachment, which possessed high HBP diversity and required more attention. These findings will help in understanding the microbial hazards in different waste components and provide guidance for the control and risk reduction of bioaerosols during waste management and recycling.


Assuntos
Aerossóis , Microbiologia do Ar , Bactérias , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Aerossóis/análise , Resíduos de Alimentos , Humanos , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/análise , Eliminação de Resíduos , Monitoramento Ambiental/métodos
4.
Nano Lett ; 23(4): 1591-1599, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36723485

RESUMO

Cells release extracellular vesicles (EVs) as the carriers for intercellular communications to regulate life activities. Particularly, it is increasingly apparent that mechanical forces play an essential role in biological systems. The nanomechanical properties of EVs and their dynamics in cancer development are still not fully understood. Herein, with the use of atomic force microscopy (AFM), the nanomechanical signatures of EVs from the liquid biopsies of hematologic cancer patients were unraveled. Single native EVs were probed by AFM under aqueous conditions. The elastic and viscous properties of EVs were measured and visualized to correlate EV mechanics with EV geometry. Experimental results remarkably reveal the significant differences in EV mechanics among multiple myeloma patients, lymphoma patients, and healthy volunteers. The study unveils the unique nanomechanical signatures of EVs in hematologic cancers, which will benefit the studies of liquid biopsies for cancer diagnosis and prognosis with translational significance.


Assuntos
Vesículas Extracelulares , Neoplasias Hematológicas , Mieloma Múltiplo , Humanos , Microscopia de Força Atômica/métodos , Biópsia Líquida
5.
Molecules ; 29(16)2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39203048

RESUMO

To synthesize an effective and versatile nano-platform serving as a promising carrier for controlled drug delivery, visible-light-induced diselenide-crosslinked polyurethane micelles were designed and prepared for ROS-triggered on-demand doxorubicin (DOX) release. A rationally designed amphiphilic block copolymer, poly(ethylene glycol)-b-poly(diselenolane diol-co-isophorone diisocyanate)-b-poly(ethylene glycol) (PEG-b-PUSe-b-PEG), which incorporates dangling diselenolane groups within the hydrophobic PU segments, was initially synthesized through the polycondensation reaction. In aqueous media, this type of amphiphilic block copolymer can self-assemble into micellar aggregates and encapsulate DOX within the micellar core, forming DOX-loaded micelles that are subsequently in situ core-crosslinked by diselenides via a visible-light-triggered metathesis reaction of Se-Se bonds. Compared with the non-crosslinked micelles (NCLMs), the as-prepared diselenide-crosslinked micelles (CLMs) exhibited a smaller particle size and improved colloidal stability. In vitro release studies have demonstrated suppressed drug release behavior for CLMs in physiological conditions, as compared to the NCLMs, whereas a burst release of DOX occurred upon exposure to an oxidation environment. Moreover, MTT assay results have revealed that the crosslinked polyurethane micelles displayed no significant cytotoxicity towards HeLa cells. Cellular uptake analyses have suggested the effective internalization of DOX-loaded crosslinked micelles and DOX release within cancer cells. These findings suggest that this kind of ROS-triggered reversibly crosslinked polyurethane micelles hold significant potential as a ROS-responsive drug delivery system.


Assuntos
Doxorrubicina , Luz , Micelas , Polímeros , Espécies Reativas de Oxigênio , Doxorrubicina/química , Doxorrubicina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Humanos , Polímeros/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Células HeLa , Polietilenoglicóis/química , Sobrevivência Celular/efeitos dos fármacos , Tamanho da Partícula
6.
Skin Res Technol ; 29(6): e13352, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37357653

RESUMO

BACKGROUND: Piebaldism is a rare, autosomal dominant, and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SLUG genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. METHODS: In this paper, we report a case of piebaldism with café-au-lait macules resulting from a novel mutation of KIT gene c.1982C > T (p.Thr661Ile) in a three-generation Chinese family. The whole-exome sequencing, mitochondrial gene 3000X, and bioinformatics tools were used to identify the mutation in this new-found pedigree. In addition, we searched the databases of "Punmed, Chinese National Knowledge Infrastructure, CMJD, WANFANG MED ONLINE", reviewed 88 cases of piebaldism caused by KIT gene mutation, and summarized the relationship between clinical phenotype and genotype of piebaldism through logistic regression and other statistical methods. RESULTS: The proband and her affected mother carried a heterozygous c.1982C > T missense mutation (p.Thr661Ile) on KIT gene. Bioinformatics analysis hinted that it had potential pathogenicity. The data showed that piebaldism patients with cafè-au-lait macules had KIT mutations almost located in the intracellular tyrosine kinase domain and were mostly related to the severe clinical phenotype of piebaldism. CONCLUSION: The new heterozygous c.1982C > T missense mutation on KIT caused piebaldism with café-au-lait macules in this Chinese family. This study provides a new reference index for clinicians to judge the severity of clinical phenotypes of piebaldism, broadens the understanding of the correlation between clinical phenotypes and genotypes of piebaldism, and provides reference of genetic counseling and prenatal diagnosis for affected families.


Assuntos
Piebaldismo , Transtornos da Pigmentação , Humanos , Feminino , Piebaldismo/genética , Proteínas Proto-Oncogênicas c-kit/genética , Manchas Café com Leite/diagnóstico , Manchas Café com Leite/genética , Mutação/genética
7.
Biochem Genet ; 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38127171

RESUMO

Circular RNAs (circRNAs) exhibit significant functions in diverse malignant tumors, including lung adenocarcinoma (LUAD). In this study, we aimed to elucidate the role of circRNA scm like with four mbt domains 2 (circSFMBT2) in LUAD. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot assay or immunohistochemistry (IHC) assay was performed for quantification of circSFMBT2, microRNA-1305 (miR-1305), spalt like transcription factor 4 (SALL4), proliferating Cell Nuclear Antigen (PCNA) or Ki-67. 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell assay and flow cytometry analysis were applied to analyze cell proliferation, metastasis and apoptosis, respectively. Mouse xenograft model was established to explore the function of circSFMBT2. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to estimate the relationship between miR-1305 and circSFMBT2 or SALL4. CircSFMBT2 was upregulated in LUAD and related to advanced TNM stage and poor prognosis. CircSFMBT2 knockdown suppressed cell proliferation, metastasis, glycolysis and induced apoptosis in LUAD cells in vitro as well as tumor formation in vivo. CircSFMBT2 directly targeted miR-1305, and miR-1305 inhibition reversed circSFMBT2 knockdown-mediated inhibitory effects on LUAD malignant behaviors. SALL4 was the target gene of miR-1305. MiR-1305 overexpression repressed the malignant phenotypes of LUAD cells, while SALL4 enhancement abated the effects. CircSFMBT2 aggravated the progression of LUAD by the miR-1305/SALL4 axis, which might provide a diagnostic and prognostic marker for LUAD.

8.
Cost Eff Resour Alloc ; 19(1): 53, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404418

RESUMO

BACKGROUND: Lung cancer is the most prevalent cancer, and the leading cause of cancer-related deaths in China. The aim of this study was to estimate the direct medical expenditure incurred for lung cancer care and analyze the trend therein for the period 2002-2011 using nationally representative data in China METHODS: This study was based on 10-year, multicenter retrospective expenditure data collected from hospital records, covering 15,437 lung cancer patients from 13 provinces diagnosed during the period 2002-2011. All expenditure data were adjusted to 2011 to eliminate the effects of inflation using China's annual consumer price index. RESULTS: The direct medical expenditure for lung cancer care (in 2011) was 39,015 CNY (US$6,041) per case, with an annual growth rate of 7.55% from 2002 to 2011. Drug costs were the highest proportionally in the total medical expenditure (54.27%), followed by treatment expenditure (14.32%) and surgical expenditure (8.10%). Medical expenditures for the disease varied based on region, hospital level, type, and stage. CONCLUSION: The medical expenditure for lung cancer care is substantial in China. Drug costs and laboratory test are the main factors increasing medical costs.

9.
Mikrochim Acta ; 188(8): 249, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34254194

RESUMO

A gold nanoparticle (AuNP)-based sensing strategy based on rapid reduction of Au(I→0) is proposed. As a proof-of-concept study, the proposed sensing principle is designed for simultaneous and colorimetric detection and discrimination of multiple proteins. In the presence of H2O2, the target proteins could reduce Au(I) (i.e. HAuCl2) to AuNPs with different sizes, shapes and dispersion/aggregation states, thus resulting in rapidly colorimetric identification of different proteins. The optical response (i.e. color) of AuNPs is found to be characteristic of a given protein. The color response patterns are characteristic for each protein and can be quantitatively differentiated by statistical techniques. The sensor array is capable of discriminating proteins at concentrations as low as 0.1 µg/mL with high accuracy. A linear relationship was observed between the total Euclidean distances and protein concentration, providing the potential for protein quantification using this sensor array. The limit of detection (LOD) for catalase (Cat) is 0.08 µg/mL. The good linear range (from 0 to 8 µg/mL) has been used for the quantitative assay of Cat. To show a potentially practical application, this method was used to detect and discriminate proteins in human urine and tear samples. Graphical abstract We report a facile gold nanoparticle (AuNP)-based sensing strategy, that is, "a rapid reduction of Au(I) to Au(0) nanoparticles with different sizes and shapes by analytes that having certain reducing capabilities, resulting in different colours." The proposed sensing principle is designed for simultaneous, colorimetric detection and discrimination of multiple proteins.


Assuntos
Colorimetria/métodos , Nanopartículas Metálicas/química , Proteínas/análise , Animais , Bovinos , Ouro/química , Humanos , Peróxido de Hidrogênio/química , Limite de Detecção , Oxirredução , Estudo de Prova de Conceito , Lágrimas/química , Urina/química
10.
J Cell Mol Med ; 24(23): 13600-13608, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33157566

RESUMO

This study aimed to explore the function of IFN-γ+ IL-17+ Th17 cells on fibrosis in systemic scleroderma (SSc). Blood and skin samples were collected from 20 SSc cases and 10 healthy individuals. The percentage of IFN-γ+ IL-17+ Th17 cells was detected using flow cytometry. The in vitro induction of IFN-γ+ IL-17+ Th17 cells was performed adopting PHA and rIL-12. Gene expression was detected via quantitative real-time polymerase chain reaction (qRT-PCR), whereas western blot analysis was adopted for protein analysis. The distribution of IFN-γ+ IL-17+ Th17 cells was significantly increased in SSc cases and positively correlated with SSc stages (P = .031), disease duration (P = .016), activity (P = .025) and skin scores (P < .001). In vitro, IFN-γ+ IL-17+ Th17 cells could promote the expressions of α-SMA and COL1A1, revealing increased fibroblasts' proliferation and enhanced collagen-secreting capacity. In addition, IL-21 expression was significantly increased in co-culture medium of IFN-γ+ IL-17+ Th17 cells and fibroblasts (P < .001). IL-21 neutralizer treatment resulted in the down-regulation of α-SMA and COL1A1. IL-21 was confirmed as an effector of IFN-γ+ IL-17+ Th17 cells in fibrosis process. The distribution of IFN-γ+ IL-17+ Th17 cells was significantly increased in SSc cases and positively correlated with disease activity. IFN-γ+ IL-17+ Th17 cells could promote fibroblast proliferation and enhance collagen-secreting ability via producing IL-21, thus contributing to fibrosis in SSc.


Assuntos
Interferon gama/metabolismo , Interleucina-17/metabolismo , Interleucinas/biossíntese , Escleroderma Sistêmico/etiologia , Escleroderma Sistêmico/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Adulto , Idoso , Autoimunidade , Biomarcadores , Diferenciação Celular/genética , Células Cultivadas , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Fibroblastos/metabolismo , Fibrose , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnóstico , Índice de Gravidade de Doença
11.
Lasers Surg Med ; 52(8): 761-767, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31919885

RESUMO

BACKGROUND AND OBJECTIVES: Alopecia areata (AA) is an autoimmune disease characterized by T cell-mediated attack on the hair follicle. Although there are a wide range of therapies, the majority of them are not satisfactory due to side effects or limited efficacy. In this study, we sought to evaluate the efficacy, influence factors, and safety of 308-nm excimer lamp with minoxidil in the treatment of AA. STUDY DESIGN/MATERIALS AND METHODS: This was a prospective, single-blinded, self-control study, using 308-nm excimer lamp with minoxidil for the treatment of AA. One selected alopecia lesion was divided into the control and treated side. Topical minoxidil (2% solution) was used on both sides, but 308-nm excimer lamp was only added to the treated side. The primary endpoint was the discrepancy of hair growth on each side. RESULTS: A total of 38 patients (24 males and 14 females) with AA were enrolled in this study, and 34 of them (21 males and 13 females) completed the whole treatment. Thirty-two (94.2%) patients achieved clinical response, and 21 (44.1%) patients achieved with >50% hair regrowth on the treated side after a 12-week treatment. The hair number and diameter on the treated side had significantly increased compared with the control side with statistical differences. Hyperpigmentation and erythema occurred on the treated side of all the patients but they were considered tolerable. Patients of younger age or with smaller area of lesion had better effect. CONCLUSIONS: The 308-nm excimer lamp with minoxidil therapy can be considered as an effective and safe treatment for single or multiple AA. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.


Assuntos
Alopecia em Áreas , Minoxidil , Alopecia , Alopecia em Áreas/diagnóstico por imagem , Alopecia em Áreas/tratamento farmacológico , Feminino , Cabelo , Humanos , Lasers de Excimer , Masculino , Estudos Prospectivos , Resultado do Tratamento
12.
Anal Chem ; 91(3): 2425-2430, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30620179

RESUMO

Exosomes (Exos) are nanoscale natural vehicles for transporting biomolecules to facilitate cell-to-cell communication, indicating a high potential of them for delivering therapeutics/diagnostics. To improve their delivery capacity, a simple, noninvasive, and efficient strategy for functionalizing Exos with effective targeting ligands as well as elucidation of the cellular uptake mechanism of these functionalized Exos was found be to necessary, but remained a challenge. In this work, we used diacyllipid-aptamer conjugates as the targeting ligand to develop an aptamer-functionalized Exos (Apt-Exos) nanoplatform for cell type-specific delivery of molecular therapeutics. The cellular uptake mechanism of Apt-Exos was investigated in details, and distinct behavior was observed in comparison to free Exos. By combining the excellent molecular recognition capability of aptamers and the superiority of Exos as natural vehicles, Apt-Exos can efficiently deliver molecular drugs/fluorophores to target cancer cells, providing a promising delivery platform for cancer theranostics.


Assuntos
Antineoplásicos/farmacologia , Aptâmeros de Nucleotídeos/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Exossomos/química , Aptâmeros de Nucleotídeos/metabolismo , Aptâmeros de Nucleotídeos/toxicidade , Linhagem Celular Tumoral , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Eletroporação , Endocitose/fisiologia , Exossomos/metabolismo , Humanos , Cinética , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Fosfolipídeos/toxicidade , Estudo de Prova de Conceito
13.
Psychooncology ; 28(9): 1836-1844, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31240803

RESUMO

OBJECTIVE: The impact of participating in breast cancer screening programmes on health-related quality of life (HRQoL)is poorly understood. METHODS: Based on a national breast cancer screening programme in China, a multicentre cross-sectional survey was conducted covering 12 provinces from September 2013 to December 2014. HRQoL of participants in the screening population and general population was evaluated by the three-levelEuroQol-five-Dimensions (EQ-5D-3L) instrument, and utility scores were generated through the Chinese value set. Univariate and multivariate regression analyses were performed to explore determinants of utility scores and anxiety/depression problems. RESULTS: For screening group and general population (n = 4756, mean age = 51.6 year old), the corresponding utility scores were 0.937 (95% CI, 0.933-0.941) and 0.953 (0.949-0.957) (P < .001). Pain/discomfort and anxiety/depression were the most common reported in both groups (51.4% and 34.3%, P < .001). Utility scores at prescreening, in-screening, and postscreening interview timings were 0.928 (0.921-0.935), 0.958 (0.948-0.969), and 0.938 (0.933-0.943), respectively (P < .001); the corresponding proportions of anxiety/depression reporting were 25.9%, 16.3%, and 21.1%, respectively (P = .004). Interview timing, geographical region, and insurance status were associated with HRQoL and anxiety/depression in women at high-risk of breast cancer. CONCLUSIONS: Utility scores of screening participants were significantly lower than that of general population in China, but the difference may be clinically insignificant. Further cohort studies using HRQoL measurements are needed.


Assuntos
Neoplasias da Mama/psicologia , Detecção Precoce de Câncer/estatística & dados numéricos , Qualidade de Vida , Adulto , Idoso , Ansiedade/epidemiologia , Neoplasias da Mama/diagnóstico , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Medição de Risco
14.
BMC Cancer ; 18(1): 435, 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29665788

RESUMO

BACKGROUND: In China, stomach cancer is the third most common cancer and the third leading cause of cancer death. Few studies have examined Chinese stomach cancer patients' medical expenses and their associated trends. The Cancer Screening Program in Urban China (CanSPUC) is a Major Public Health Project funded by the central government. Through this project, we have extracted patients' medical expenses from hospital billing data to examine the costs of the first course treatments (which refers to 2 months before and 10 months after the date of cancer diagnosis) in Chinese patients with stomach cancer and the associated trends. METHODS: The expense data of 14,692 urban Chinese patients with stomach cancer were collected from 40 hospitals in 13 provinces. We estimated the inflation-adjusted medical expenses per patient during 2002-2011. We described the time trends of medical expenses at the country-level, and those trends by subgroup, and analyzed the compositions of medical expenses. We constructed the Generalized Linear Mixed (GLM) regression model with Poisson distribution to examine the factors that were associated with medical expenses per patient. RESULTS: The average medical expenses of the first course treatments were about 43,249 CNY (6851 USD) in 2011, more than twice of that in 2002. The expenses increased by an average annual rate of 7.4%. Longer stay during hospitalization and an increased number of episodes of care are the two main contributors to the expense increase. The upward trend of medical expenses was observed in almost all patient subgroups. Drug expenses accounted for over half of the medical expenses. CONCLUSIONS: The average medical expenses of the first course (2 months before and 10 months after the date of cancer diagnosis) treatments per stomach cancer patient in urban China in 2011 were doubled during the previous 10 years, and about twice as high as the per capita disposable income of urban households in the same year. Such high expenses indicate that it makes economic sense to invest in cancer prevention and control in China.


Assuntos
Gastos em Saúde , Hospitalização , Neoplasias Gástricas/epidemiologia , Saúde da População Urbana , Idoso , Feminino , História do Século XXI , Hospitalização/economia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/história , Neoplasias Gástricas/terapia
15.
Mol Cell Biochem ; 449(1-2): 285-294, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29761248

RESUMO

Biglycan (BGN) is overexpressed in cancer stem cells of colon cancer and induces the activation of NF-κB pathway which contributes to the chemotherapy resistance of diverse cancer types. Therefore, we hypothesized that the overexpression of BGN also promoted the development of multiple drug resistance (MDR) in colon cancer via NF-κB pathway. The expression of BGN was bilaterally modulated in colon cancer cell lines HT-29 and SW-480 and the effect of treatments on the cell proliferation and resistance to 5-FU was assessed. Moreover, the role of NF-κB signaling in the BGN-mediated formation of MDR was further investigated by subjecting BGN-overexpressed SW-480 cells to the co-treatment of chemo-agents and NF-κB inhibitor, PDTC. The inhibition of BGN expression decreased the proliferation potential of HT-29 cells while the induction of BGN expression increased the potential of SW-480 cells. BGN knockdown increased HT-29 cells' sensitivity to 5-FU, represented by the lower colony number and higher apoptotic rate. To the contrary, BGN overexpression promoted the resistance of SW-480 cells to 5-FU. The effect of BGN modulation on colon cancer cells was associated with the changes in apoptosis and NF-κB pathways: BGN inhibition increased the expressions of pro-apoptosis indicators and suppressed NF-κB pathway activity while BGN overexpression had the opposite effect. It was also found that the BGN-mediated formation of MDR was impaired when NF-κB pathway was blocked. Findings outlined in the current study showed that BGN contributed to the formation of chemotherapy resistance in colon cancer cells by activating NF-κB signaling.


Assuntos
Biglicano/metabolismo , Neoplasias do Colo/tratamento farmacológico , Resistência a Múltiplos Medicamentos , Fluoruracila/farmacologia , Transdução de Sinais , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/fisiopatologia , Fluoruracila/uso terapêutico , Células HT29 , Humanos , NF-kappa B/metabolismo
17.
Tumour Biol ; 36(3): 1773-80, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25371074

RESUMO

Biglycan is an important component of the extracellular matrix, which belongs to the small leucine-rich proteoglycan family. Recent studies have shown that biglycan expression is elevated in many tumor tissues and implies poor prognosis, such as colon cancer. However, the molecular mechanism of biglycan in colon cancer has not been investigated. The present study aimed to investigate the effects of biglycan on vascular endothelial growth factor (VEGF) expression in colon cancer cells and on tumor angiogenesis in vivo. Biglycan overexpression vectors were constructed, and the stable biglycan overexpression in human colon cancer cell lines (HCT116 cells) was established by G418 screening. The stable cell clones were subsequently used to initiate tumor xenografts in nude mice. Our results showed that biglycan overexpression notably up-regulated the levels of VEGF in colon cancer cells, which was further confirmed by immunohistochemistry analysis in the xenograft colon tumors. Moreover, high levels of biglycan promoted angiogenesis and colon tumor growth, as evidenced by the increased cell viability, colon tumor size, and weight, as well as the CD34 expression. Additionally, we found that the extracellular signal-regulated kinase (ERK) signaling pathway was activated by biglycan in colon cancer cells. The ERK inhibitor PD98059 dramatically reversed the increased expression of VEGF induced by biglycan. Taken together, our results indicated that biglycan up-regulated VEGF expression in colon cancer cells and promoted tumor angiogenesis. Biglycan-mediated VEGF regulation may correlate with the activation of the ERK signaling pathway. Therefore, biglycan may be a promising target for anti-angiogenic therapy for cancer.


Assuntos
Biglicano/farmacologia , Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Antígenos CD34/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética
18.
Analyst ; 140(5): 1572-7, 2015 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-25597304

RESUMO

A novel strategy for the fabrication of a colorimetric aptasensor using label free gold nanoparticles (AuNPs) is proposed in this work, and the strategy has been employed for the assay of adenosine deaminase (ADA) activity. The aptasensor consists of adenosine (AD) aptamer, AD and AuNPs. The design of the biosensor takes advantage of the special optical properties of AuNPs and the interaction between AuNPs and single-strand DNA. In the absence of ADA, the AuNPs are aggregated and are blue in color under appropriate salt concentration because of the grid structure of an AD aptamer when binding to AD, while in the presence of the analyte, AuNPs remain dispersed with red color under the same concentration of salt owing to ADA converting AD into inosine which has no affinity with the AD aptamer, thus allowing quantitative investigation of ADA activity. The present strategy is simple, cost-effective, selective and sensitive for ADA with a detection limit of 1.526 U L(-1), which is about one order of magnitude lower than that previously reported. In addition, a very low concentration of the inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) could generate a distinguishable response. Therefore, the AuNP-based colorimetric biosensor has great potential in the diagnosis of ADA-relevant diseases and drug screening.


Assuntos
Adenosina Desaminase/análise , Aptâmeros de Nucleotídeos/química , Bioensaio/métodos , Técnicas Biossensoriais/métodos , Colorimetria/métodos , Ouro/química , Nanopartículas Metálicas/química , Adenosina/metabolismo , Adenosina Desaminase/química , Adenosina Desaminase/metabolismo , Inibidores de Adenosina Desaminase/farmacologia , Humanos , Limite de Detecção
19.
Small ; 10(16): 3412-20, 2014 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-24788855

RESUMO

A novel fluorescence turn-on strategy, based on the resistance of metal-mediated molecular-beacons (MBs) toward nuclease digestion and the remarkable difference in the affinity of graphene oxide (GO) with MBs and the mononucleotides, is designed for the biothiols assay. Specifically, the metal-mediated base pairs facilitate the dye labeled MBs to fold into a hairpin structure preventing the digestion by exonuclease I, and thus allow the fluorescence quenching. The competition binding by biothiols removes metal ions from the base pairs, causing the nuclease reaction, and less decrease in the fluorescence is obtained after incubating with GO due to the weak affinity of the product-mononucleotides to GO. Hg(2+)-mediated MBs were firstly designed for the biothiols detection, and glutathione (GSH) was applied as the model target. Under the optimal conditions, the approach exhibits high sensitivity to GSH with a detection limit of 1.53 nM. Ag(+)-mediated MBs based sensor was also constructed to demonstrate its versatility, and cysteine was studied as the model target. The satisfactory results in the determination of biothiols in serum demonstrate that the method possesses great potential for detecting thiols in biological fluids. This new approach is expected to promote the exploitation of metal-mediated base pairs-based biosensors in biochemical and biomedical studies.


Assuntos
Pareamento de Bases , Exodesoxirribonucleases/química , Glutationa/análise , Grafite/química , Compostos de Sulfidrila/análise , Limite de Detecção , Óxidos/química , Espectrometria de Fluorescência
20.
Tumour Biol ; 35(10): 10515-22, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25060179

RESUMO

This meta-analysis aimed to identify the value of serum matrix metalloproteinase-7 (MMP-7) levels for the diagnosis of colorectal cancer (CRC). Through searching the following electronic databases: Cochrane Library (Issue 12, 2014), Web of Science (1945∼2014), PubMed (1966∼2014), CINAHL (1982∼2014), EMBASE (1980∼2014), and CBM (1982∼2014), related articles were determined without any language restrictions. Stata statistical software (Version 12.0, Stata Corporation, College Station, TX, USA) was chosen to deal with statistical data. Standard mean difference (SMD) and its corresponding 95 % confidence interval (95 % CI) were calculated to clarify the correlation between serum MMP-7 levels and CRC. Seven clinical case-control studies which recruited 430 CRC patients and 357 healthy subjects were selected for statistical analysis. The main findings of our meta-analysis showed that the serum MMP-7 level in CRC patients was significantly higher than that in control subjects (SMD = 2.15, 95 % CI = 1.46∼2.84, P < 0.001). Ethnicity-stratified analysis indicated a higher serum MMP-7 level in CRC patients than that of control subjects among the Asians and the Caucasians (Asians: SMD = 2.83, 95 % CI = 1.76∼3.91, P < 0.001; Caucasians: SMD = 1.06, 95 % CI = 0.46∼1.66, P = 0.001; respectively). The present meta-analysis indicated that the increased serum level of MMP-7 may be connected with the development of CRC; thus, serum levels of MMP-7 could be an independent biomarker for CRC patients.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Metaloproteinase 7 da Matriz/sangue , Neoplasias Colorretais/enzimologia , Humanos
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