RESUMO
Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer and its incidence is rising globally. The molecular mechanisms of PTC progression remain unclear, hindering the development of effective treatments. This study focuses on hsa_circ_0008016 (circFGFR1), a circular RNA significantly up-regulated in PTC cells. Silencing circFGFR1 inhibited PTC cell proliferation and increased cell apoptosis, suggesting its role in PTC progression. The RNA-binding protein FUS was identified as a promoter of circFGFR1 formation. While circFGFR1 does not influence FGFR1 mRNA translation, it inhibits ubiquitination and degradation of FGFR1 protein, prolonging its half-life. CircFGFR1 also interacts with protein CBL, inhibiting CBL-mediated ubiquitination of FGFR1 proteins. Rescue assays confirmed circFGFR1 promotes PTC cell growth through mediating FGFR1. This study highlights the potential of circFGFR1 as a therapeutic target, offering insights into PTC's molecular mechanisms, and paving the way for novel treatment strategies.
Assuntos
RNA Circular , Proteína FUS de Ligação a RNA , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Humanos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , RNA Circular/genética , RNA Circular/metabolismo , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismo , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Apoptose , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-cbl/genética , Proteínas Proto-Oncogênicas c-cbl/metabolismo , UbiquitinaçãoRESUMO
BACKGROUND: The tumor microenvironment (TME) in breast cancer plays a vital role in occurrence, development, and therapeutic responses. However, immune and stroma constituents in the TME are major obstacles to understanding and treating breast cancer. We evaluated the significance of TME-related genes in breast cancer. METHODS: Invasive breast cancer (BRCA) samples were retrieved from the TCGA and GEO databases. Stroma and immune scores of samples as well as the proportion of tumor infiltrating immune cells (TICs) were calculated using the ESTIMATE and CIBERSORT algorithms. TME-related differentially expressed genes (DEGs) were analyzed by a protein interaction (PPI) network and univariate Cox regression to determine CD1C as a hub gene. Subsequently, the prognostic value of CD1C, its response to immunotherapy, and its mechanism in the TME were further studied. RESULTS: In BRCA, DEGs were determined to identify CD1C as a hub gene. The expression level of CD1C in BRCA patients was verified based on the TCGA database, polymerase chain reaction (PCR) results, and western blot analysis. Immunohistochemical staining (IHC) results revealed a correlation between prognosis, clinical features, and CD1C expression in BRCA. Enrichment analysis of GSEA and GSVA showed that CD1C participates in immune-associated signaling pathways. CIBERSORT showed that CD1C levels were associated with tumor immune infiltrating cells (TILs), such as different kinds of T cells. Gene co-expression analysis showed that CD1C and the majority of immune-associated genes were co-expressed in BRCA. In renal cell carcinoma, patients with a high expression of CD1C had a better immunotherapy effect. CONCLUSION: CD1C is an important part of the TME and participates in immune activity regulation in breast tumors. CD1C is expected to become a prognostic marker and a new treatment target for breast cancer.
Assuntos
Antígenos CD1 , Neoplasias da Mama , Glicoproteínas , Feminino , Humanos , Antígenos CD1/genética , Mama , Neoplasias da Mama/genética , Glicoproteínas/genética , Prognóstico , Microambiente Tumoral/genéticaRESUMO
Sulfoxide-bridged dimeric BODIPYs were developed as a new class of long-wavelength photoconvertible fluorophores. Upon visible-light irradiation, a sulfoxide moiety was released to generate the corresponding α,α-directly linked dimeric BODIPYs. The extrusion of SO from sulfoxides was mainly through an intramolecular fashion involving reactive triplet states. By this photoconversion, not only were more than 100 nm red shifts of absorption and emission maxima (up to 648/714 nm) achieved but also stable products with bright fluorescence were produced with high efficiency. The combination of photoactivation and red-shifted excitation/emission offered optimal contrast and eliminated the interference from biological autofluorescence. More importantly, the in situ products of these visible-light-induced reactions demonstrated ideal single-molecule fluorescence properties in the near-infrared region. Therefore, this new photoconversion could be a powerful photoactivation method achieving super-resolution single-molecule localization imaging in a living cell without using UV illumination and cell-toxic additives.
Assuntos
Fotoquímica , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Multimodal lateral flow immunoassay (LFIA) has shown promise for improving both the flexibility and practicability of point-of-care test. We report here a facile, in situ growth method for preparing multifunctional core-shell-shell nano-sunflowers with a unique combination of color-magnetic-Raman properties. The use of Fe3O4 nanobeads with high saturation magnetization as the magnetic core allowed for robust magnetic signal strength-even after successive coatings of polydopamine and gold nanoparticles (Au NPs). Carefully selected 4-mercaptobenzonitrile molecules not only contributed to the growth of the Au NP shell but also generated a strong, surface-enhanced Raman scattering signal. The resulting nanomaterials were successfully used in the construction of multimodal LFIA with one qualitative and two alternative quantitative detection modes of different sensitivity levels. The limit of detection for the paradigm target-human chorionic gonadotropin-was 10 mIU/mL in color mode, 1.2 mIU/mL in magnetic mode, and 0.2 mIU/mL in Raman mode.
Assuntos
Helianthus , Nanopartículas Metálicas , Ouro , Humanos , Imunoensaio , Fenômenos Magnéticos , Análise Espectral RamanRESUMO
Krüppel-homolog 1 (Kr-h1), a zinc-finger transcription factor, inhibits larval metamorphosis and promotes adult reproduction by transducing juvenile hormone (JH). Although the transcriptional regulation of Kr-h1 has been extensively studied, little is known about its regulation at the post-transcriptional level. Using the migratory locust Locusta migratoria as a model system, we report here that the microRNAs let-7 and miR-278 bound to the Kr-h1 coding sequence and downregulated its expression. Application of let-7 and miR-278 mimics (agomiRs) significantly reduced the level of Kr-h1 transcripts, resulting in partially precocious metamorphosis in nymphs as well as markedly decreased yolk protein precursors, arrested ovarian development and blocked oocyte maturation in adults. Moreover, the expression of let-7 and miR-278 was repressed by JH, constituting a regulatory loop of JH signaling. This study thus reveals a previously unknown regulatory mechanism whereby JH suppresses the expression of let-7 and miR-278, which, together with JH induction of Kr-h1 transcription, prevents the precocious metamorphosis of nymphs and stimulates the reproduction of adult females. These results advance our understanding of the coordination of JH and miRNA regulation in insect development.
Assuntos
Genes de Insetos , Gafanhotos/crescimento & desenvolvimento , Gafanhotos/genética , Hormônios Juvenis/farmacologia , Fatores de Transcrição Kruppel-Like/genética , Metamorfose Biológica/genética , MicroRNAs/metabolismo , Oogênese/genética , Animais , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gafanhotos/efeitos dos fármacos , Fatores de Transcrição Kruppel-Like/metabolismo , Metamorfose Biológica/efeitos dos fármacos , MicroRNAs/genética , Oócitos/metabolismo , Oogênese/efeitos dos fármacos , Óvulo/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Tempo , Vitelogênese/efeitos dos fármacos , Vitelogênese/genéticaRESUMO
A Cu(I)-promoted oxidative dimerization of BODIPY dyes was developed to give a series of α,α- ethylene-bridged BODIPY dimers and trimers for the first time. This methodology does not need harsh conditions but relies on the singlet-electron-transfer process between alkylated BODIPYs and Cu(I) salt to generate BODIPY-based radical species, which undergo a selective radical homocoupling reaction. Moreover, these resultant dimers and trimers showed high attenuation coefficients, small line widths of the absorption and emission, and intense fluorescence.
Assuntos
Elétrons , Corantes Fluorescentes , Compostos de Boro , Etilenos , Estrutura MolecularRESUMO
A new family of π-extended BODIPY derivatives were obtained through the condensation of aldehyde and pyrrole in aqueous solution in the presence of HCl. The new rigid π-framework extends beyond the dipyrromethene unit, which is significantly different from classical BODIPYs in the electronic configuration. Both π-extended BODIPYs displayed intense absorption and moderate emission with maxima around 565 and 620 nm, respectively, and showed interesting reactivity toward various nucleophiles. Moreover, these π-extended BODIPYs were developed as fluorescent probes for rapid and selective detection of GSH and were successfully applied for live-cell imaging.
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Compostos de Boro , Corantes Fluorescentes , PirróisRESUMO
Reticulate evolution resulting from hybridization and introgression has been recognized as a creative source of species and diversification in bamboos. Previous phylogenetic studies revealed that Fargesia (s.l.) (Fargesia and Yushania) was divided into the Fargesia spathe clade and the non-spathe clade. Interestingly, the Fargesia spathe clade may have originated from hybridization among other clades within Fargesia (s.l.). Understanding the hybrid origin of this clade requires a robust phylogenetic framework in which major clades within Fargesia (s.l.) are resolved. Here, we used three nuclear genes to reconstruct the evolutionary history of Fargesia (s.l.) and its allies to identify putative patterns in the origin of the Fargesia spathe clade and to examine the extent to which reticulate evolution has occurred at the interspecific level in bamboos. Bashania species form a clade with Fargesia (s.l.), which is further divided into Group I and Group II. The Fargesia spathe clade, the Alpine Bashania clade, and Fargesia yajiangensis comprise Group I, while the Bashania fargesii clade and the remaining Fargesia (s.l.) species form Group II. Incongruence between the current nuclear-based and previous plastid phylogenies demonstrate several possible hybridization events among Fargesia (s.l.) species and related taxa, which have given rise to the Fargesia spathe clade, the Phyllostachys clade, and the Ampelocalamus clade. We also detected several putative hybrid species of Fargesia (s.l.). Our results show that reticulate evolution has played a prominent role in Fargesia (s.l.) evolution, which could, in part, account for the taxonomic difficulty associated with Fargesia (s.l.) and the alpine bamboos. The study also underscores the importance of hybridization in the evolution of bamboos, at both intergeneric and intrageneric levels.
Assuntos
Núcleo Celular/genética , Evolução Molecular , Poaceae/genética , Sequência de Bases , Teorema de Bayes , Bases de Dados Genéticas , Genes de Plantas , Marcadores Genéticos , Hibridização Genética , Filogenia , Poaceae/anatomia & histologiaRESUMO
A novel green hydrophilic levofloxacin imprinted polymer was presented via one-step polymerization in water using ionic liquid 1,6-hexa-3,3'-bis-1-vinylimidazolium bromine with multiple hydrophilic groups and 2-hydroxyethyl methacrylate as a co-functional monomer. Adsorption experiment revealed that the ionic liquid significantly improved the water compatible of imprinted polymer, and the excellent recognition of molecularly imprinted polymer for levofloxacin in water corresponds to the synergetic effect of H-bonding and the electrostatic and π-π interactions between the levofloxacin and co-functional monomer. Furthermore, the adsorption process of the imprinted material towards levofloxacin fitted the Langmuir model, and the maximum binding amount of levofloxacin onto the imprinted and corresponding non-imprinted polymer were 16.45 and 6.82 mg/g at 25°C, respectively. After optimizing the parameters affecting solid phase extraction performance, an enrichment and determination system was achieved to separate and detect levofloxacin from water and sediment samples with recoveries that ranged from 83.67 to 101.33% and relative standard deviation of less than 5.59%.
Assuntos
Líquidos Iônicos/química , Levofloxacino/análise , Polímeros/química , Poluentes Químicos da Água/análise , Água/química , Interações Hidrofóbicas e Hidrofílicas , Estrutura MolecularRESUMO
PURPOSE: Germline variants in double-strand DNA damage repair (dsDDR) genes (e.g., BRCA1/2) predispose to pancreatic adenocarcinoma (PDAC) and may predict sensitivity to platinum-based chemotherapy and poly(ADP) ribose polymerase (PARP) inhibitors. We sought to determine the prevalence and significance of germline cancer susceptibility gene variants in PDAC with paired somatic and survival analyses. METHODS: Using a customized next-generation sequencing panel, germline/somatic DNA was analyzed from 289 patients with resected PDAC ascertained without preselection for high-risk features (e.g., young age, personal/family history). All identified variants were assessed for pathogenicity. Outcomes were analyzed using multivariable-adjusted Cox proportional hazards regression. RESULTS: We found that 28/289 (9.7%; 95% confidence interval [CI] 6.5-13.7%) patients carried pathogenic/likely pathogenic germline variants, including 21 (7.3%) dsDDR gene variants (3 BRCA1, 4 BRCA2, 14 other dsDDR genes [ATM, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C]), 3 Lynch syndrome, and 4 other genes (APC p.I1307K, CDKN2A, TP53). Somatic sequencing and immunohistochemistry identified second hits in the tumor in 12/27 (44.4%) patients with germline variants (1 failed sequencing). Compared with noncarriers, patients with germline dsDDR gene variants had superior overall survival (hazard ratio [HR] 0.54; 95% CI 0.30-0.99; P = 0.05). CONCLUSION: Nearly 10% of PDAC patients harbor germline variants, although the majority lack somatic second hits, the therapeutic significance of which warrants further study.
Assuntos
Adenocarcinoma/genética , Predisposição Genética para Doença , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Quebras de DNA de Cadeia Dupla , Intervalo Livre de Doença , Etnicidade/genética , Feminino , Mutação em Linhagem Germinativa/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgiaRESUMO
Evidence indicates a complex link between microbiota, tumor characteristics, and host immunity in the tumor microenvironment. In experimental studies, bifidobacteria appear to modulate intestinal epithelial cell differentiation. Accumulating evidence suggests that bifidobacteria may enhance the antitumor immunity and efficacy of immunotherapy. We hypothesized that the amount of bifidobacteria in colorectal carcinoma tissue might be associated with tumor differentiation and higher immune response to colorectal cancer. Using a molecular pathologic epidemiology database of 1313 rectal and colon cancers, we measured the amount of Bifidobacterium DNA in carcinoma tissue by a quantitative PCR assay. The multivariable regression model was used to adjust for potential confounders, including microsatellite instability status, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Intratumor bifidobacteria were detected in 393 cases (30%). The amount of bifidobacteria was associated with the extent of signet ring cells (P = 0.002). Compared with Bifidobacterium-negative cases, multivariable odd ratios for the extent of signet ring cells were 1.29 (95% CI, 0.74-2.24) for Bifidobacterium-low cases and 1.87 (95% CI, 1.16-3.02) for Bifidobacterium-high cases (Ptrend = 0.01). The association between intratumor bifidobacteria and signet ring cells suggests a possible role of bifidobacteria in determining distinct tumor characteristics or as an indicator of dysfunctional mucosal barrier in colorectal cancer.
Assuntos
Infecções por Bifidobacteriales/microbiologia , Bifidobacterium/genética , Biomarcadores Tumorais/genética , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Colorretais/patologia , DNA Bacteriano/genética , Adulto , Idoso , Infecções por Bifidobacteriales/genética , Infecções por Bifidobacteriales/patologia , Carcinoma de Células em Anel de Sinete/genética , Carcinoma de Células em Anel de Sinete/microbiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/microbiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Microambiente TumoralRESUMO
Pesticides are biological or chemical substances used to manage pests and diseases. Encapsulation of pesticides in biodegradable carriers creates a slow-release system that can improve water dispersibility and prolong residual activity. We prepared two kinds of poly (lactic-co-glycolic acid)(PLGA) nanoparticles (NPs) with polyvinyl alcohol (PVA) and sodium dodecyl sulfate (SDS) surfactants. These were used to encapsulate the fungicide fluazinam (Flu) against Rhizoctonia solani using the Shirasu Porous Glass (SPG) membrane emulsification method. Both nanoparticles had uniform spherical shapes with average diameters of 314.13 nm (SDS) and 612.80 nm (PVA). The slow-release microspheres had excellent sustained-release properties, resistance to UV degradation, storage stability, leaf surface coverage and antifungal efficacy compared to the commercial formulation.
Assuntos
Aminopiridinas/farmacocinética , Fungicidas Industriais/farmacocinética , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Aminopiridinas/farmacologia , Fungicidas Industriais/farmacologia , Microesferas , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo , Álcool de Polivinil/química , Porosidade , Rhizoctonia/efeitos dos fármacos , Dodecilsulfato de Sódio/química , Espectrofotometria Ultravioleta , Tensoativos/químicaRESUMO
The use of X-rays instead of UV/Vis light to trigger photodynamic therapy, named X-ray inducible photodynamic therapy, holds tremendous promise due to a high penetration capacity in tissues and is worthy of in-depth study. In this study, a novel multifunctional nanoagent based on Merocyanine 540-coupled Gd2 (WO4 )3 :Tb nanoscintillators and the vitalization of its abilities for dual-modal computed tomography and the magnetic-resonance-imaging-guided synergistic radio-/X-ray inducible photodynamic therapy of tumors is reported. Synergistic therapies show a higher tumor growth inhibition efficiency at a lower X-ray dose than radiotherapy alone. Through this proof-of-concept work, a way to tactfully understand and utilize nanoscintillators for cancer theranostics is shown.
Assuntos
Neoplasias da Mama/diagnóstico , Gadolínio/química , Imageamento por Ressonância Magnética , Fotoquimioterapia , Térbio/química , Tomografia Computadorizada por Raios X , Tungstênio/química , Animais , Neoplasias da Mama/terapia , Linhagem Celular , Feminino , Humanos , Camundongos , Nanoestruturas/química , Tamanho da Partícula , Raios XRESUMO
BACKGROUND & AIMS: Western and prudent dietary patterns have been associated with higher and lower risks of colorectal cancer (CRC), respectively. However, little is known about the associations between dietary patterns and specific anatomic subsites or molecular subtypes of CRC. METHODS: We used multivariable Cox proportional hazards models to examine the associations between Western and prudent dietary patterns and CRC risk in the Health Professionals Follow-up Study and Nurses' Health Study. RESULTS: After up to 32 years of follow-up of 137,217 men and women, we documented 3260 cases of CRC. Among individuals from whom subsite data were available, we observed 1264 proximal colon, 866 distal colon, and 670 rectal tumors. Western diet was associated with an increased incidence of CRC (Ptrend < .0001), with a relative risk (RR) of 1.31 (95% CI, 1.15-1.48, comparing the highest to lowest quartile). The association of Western diet with CRC was evident for tumors of the distal colon (RR, 1.55; 95% CI, 1.22-1.96; Ptrend = .0004) and rectum (RR, 1.35; 95% CI, 1.03-1.77; Ptrend = .01) but not proximal colon (RR, 1.11; 95% CI, 0.91-1.35; Ptrend = .51) when we comparing extreme quartiles. In contrast, for the prudent pattern, we observed a RR of 0.86 for overall CRC (95% CI, 0.77-0.95; Ptrend = .01), with similar trends at anatomic subsites. However, the trend appeared stronger among men than women. Among 1285 cases (39%) with tissue available for molecular profiling, Western diet appeared to be more strongly associated with some CRC molecular subtypes (no mutations in KRAS [KRAS wildtype] or BRAF [BRAF wildtype], no or a low CpG island methylator phenotype, and microsatellite stability), although formal tests for heterogeneity did not produce statistically significant results. CONCLUSIONS: Western dietary patterns are associated with an increased risk of CRC, particularly distal colon and rectal tumors. Western dietary patterns also appear more strongly associated with tumors that are KRAS wildtype, BRAF wildtype, have no or a low CpG island methylator phenotype, and microsatellite stability. In contrast, prudent dietary patterns are associated with a lower risk of CRC that does not vary according to anatomic subsite or molecular subtype.
Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Dieta Saudável , Dieta Ocidental/efeitos adversos , Comportamento Alimentar , Comportamento de Redução do Risco , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ilhas de CpG , Metilação de DNA , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Epidemiologia Molecular , Análise Multivariada , Mutação , Enfermeiras e Enfermeiros , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Proteção , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
BACKGROUND & AIMS: Dietary patterns affect systemic and local intestinal inflammation, which have been linked to colorectal carcinogenesis. Chronic inflammation can interfere with the adaptive immune response. We investigated whether the association of a diet that promotes intestinal inflammation with risk of colorectal carcinoma was stronger for tumors with lower lymphocytic reactions than tumors with higher lymphocytic reactions. METHODS: We collected data from the molecular pathological epidemiology databases of 2 prospective cohort studies: the Nurses' Health Study (since 1976) and the Health Professionals Follow-Up Study (since 1986). We used duplication-method time-varying Cox proportional cause-specific hazards regression to assess the association of empirical dietary inflammatory pattern (EDIP) score (derived from food frequency questionnaire data) with colorectal carcinoma subtype. Foods that contribute to high EDIP scores include red and processed meats, refined grains, carbonated beverages, and some vegetables; foods that contribute to low EDIP scores include beer, wine, coffee, tea, yellow and leafy vegetables, and fruit juice. Colorectal tissue samples were analyzed histologically for patterns of lymphocytic reactions (Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes). RESULTS: During follow-up of 124,433 participants, we documented 1311 incident colon and rectal cancer cases with available tissue data. The association between the EDIP and colorectal cancer risk was significant (Ptrend = .02), and varied with degree of peritumoral lymphocytic reaction (Pheterogeneity < .001). Higher EDIP scores were associated with increased risk of colorectal cancer with an absent or low peritumoral lymphocytic reaction (highest vs lowest EDIP score quintile hazard ratio, 2.60; 95% confidence interval, 1.60-4.23; Ptrend < .001), but not risk of tumors with intermediate or high peritumoral lymphocytic reaction (Ptrend > .80). CONCLUSIONS: In 2 prospective cohort studies, we associated inflammatory diets with a higher risk of colorectal cancer subtype that contains little or no peritumoral lymphocytic reaction. These findings suggest that diet-related inflammation might contribute to development of colorectal cancer, by suppressing the adaptive anti-tumor immune response.
Assuntos
Neoplasias Colorretais/imunologia , Dieta/efeitos adversos , Comportamento Alimentar , Doenças Inflamatórias Intestinais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Evasão Tumoral , Adulto , Idoso , Biópsia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
BACKGROUND & AIMS: Specific nutritional components are likely to induce intestinal inflammation, which is characterized by increased levels of interleukin 6 (IL6), C-reactive protein (CRP), and tumor necrosis factor-receptor superfamily member 1B (TNFRSF1B) in the circulation and promotes colorectal carcinogenesis. The inflammatory effects of a diet can be estimated based on an empiric dietary inflammatory pattern (EDIP) score, calculated based on intake of 18 foods associated with plasma levels of IL6, CRP, and TNFRSF1B. An inflammatory environment in the colon (based on increased levels of IL6, CRP, and TNFRSF1B in peripheral blood) contributes to impairment of the mucosal barrier and altered immune cell responses, affecting the composition of the intestinal microbiota. Colonization by Fusobacterium nucleatum has been associated with the presence and features of colorectal adenocarcinoma. We investigated the association between diets that promote inflammation (based on EDIP score) and colorectal cancer subtypes classified by level of F nucleatum in the tumor microenvironment. METHODS: We calculated EDIP scores based on answers to food frequency questionnaires collected from participants in the Nurses' Health Study (through June 1, 2012) and the Health Professionals Follow-up Study (through January 31, 2012). Participants in both cohorts reported diagnoses of rectal or colon cancer in biennial questionnaires; deaths from unreported colorectal cancer cases were identified through the National Death Index and next of kin. Colorectal tumor tissues were collected from hospitals where the patients underwent tumor resection and F nucleatum DNA was quantified by a polymerase chain reaction assay. We used multivariable duplication-method Cox proportional hazard regression to assess the associations of EDIP scores with risks of colorectal cancer subclassified by F nucleatum status. RESULTS: During 28 years of follow-up evaluation of 124,433 participants, we documented 951 incident cases of colorectal carcinoma with tissue F nucleatum data. Higher EDIP scores were associated with increased risk of F nucleatum-positive colorectal tumors (Ptrend = .03); for subjects in the highest vs lowest EDIP score tertiles, the hazard ratio for F nucleatum-positive colorectal tumors was 1.63 (95% CI, 1.03-2.58). EDIP scores did not associate with F nucleatum-negative tumors (Ptrend = .44). High EDIP scores associated with proximal F nucleatum-positive colorectal tumors but not with proximal F nucleatum-negative colorectal tumors (Pheterogeneity = .003). CONCLUSIONS: Diets that may promote intestinal inflammation, based on EDIP score, are associated with increased risk of F nucleatum-positive colorectal carcinomas, but not carcinomas that do not contain these bacteria. These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis; nutritional interventions might be used in precision medicine and cancer prevention.
Assuntos
Colite/complicações , Colite/microbiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Dieta/efeitos adversos , Infecções por Fusobacterium/complicações , Fusobacterium nucleatum/isolamento & purificação , Adulto , Idoso , Feminino , Seguimentos , Infecções por Fusobacterium/microbiologia , Humanos , Pessoa de Meia-IdadeRESUMO
In order to improve accuracy of aerosol measurements, a novel method using twin scanning lidars is presented; this method is able to overcome the incomplete overlap range of vertical lidar as well as provide 2D spatial distributions. The scanning lidar setups in the opposite directions are employed as remote sensing tools. Aerosol measurements are performed with cross scanning from the ground to the height of interest. Aerosol optical properties are retrieved using numerical approximation, in which differences between the measured values and the constructed values of the logarithmic range-square-corrected lidar data in the cross-scanning region are minimized. In the data retrieval, we utilize a matrix formulation, in which a Cartesian 2D range-height-indicator diagram is constructed. To verify this method, scanning measurements by ultraviolet Mie scanning lidar performed at different time intervals were taken as the cross-scanning measurements from the twin scanning lidars. With the retrieved spatial distributions of aerosol optical properties, such as aerosol backscatter, aerosol extinction, and lidar ratio, the regional aerosol studies showed that aerosol loading was relatively small and in the presence of multiple layers, which may be influenced by airflow from long-range transportation and cause a large impact on the local environment. To conclude, the presented method using twin scanning lidars is feasible for aerosol measurement in the application of horizontally atmospheric inhomogeneity.
RESUMO
The soluble form of the transmembrane glycoprotein, FcεRIα which corresponds to the high-affinity receptor for IgE, is found in serum. Growing evidence suggests the pathogenic role of IgE and FcεRI in systemic lupus erythematosus (SLE). The goal of this study is to develop a sensitive and standardized cytometric assay for quantification of sFcεRIα. A membrane emulsification technique was utilized to incorporate CuInS2 /ZnS quantum dots and Fe3 O4 nanoparticles into poly (styrene-co-maleic anhydride) microbeads. The beads were then carboxylated and coated with capture antibody monoclonal anti-human FcεRIα. This antibody binds to FcεRIα but does not block the binding of FcεRIα to IgE. After incubation with standards or serum samples, the microbeads were incubated with excessive native human IgE, followed by incubation with Phycoerythrin (PE) conjugated anti-human IgE. The resulting quantum dot microbeads were gated, and sFcεRIα quantification was analyzed based on PE fluorescence intensity. The method exhibited good linearity (R2 > 0.99), and the limit of detection was established at 0.29 ng/mL with the dynamic range of up to 200 ng/mL. The precision of the assay validated by intra- and inter-assay variability met the acceptance criteria with the mean recovery falling within 80-110% of the theoretical concentration and a corresponding CV < 20%. We tested 149 serum samples which 89 were from SLE patients and 60 were from healthy volunteers. For the first time, we detected an increased sFcεRIα level in the serum of SLE patients, which was confirmed by a commercial ELISA kit. Compared to ELISA, this novel method is more sensitive and efficient. It allows for the simple comparative analysis of sFcεRIα levels in health and disease. © 2017 International Society for Advancement of Cytometry.
Assuntos
Basófilos/citologia , Pontos Quânticos/análise , Receptores de IgE/sangue , Basófilos/imunologia , Citometria de Fluxo/métodos , Humanos , Hipersensibilidade , Imunoglobulina E/sangue , MicroesferasRESUMO
Antimicrobial peptides (AMPs) are small effectors in host defense by directly targeting microorganisms or by indirectly modulating immune responses. In the present study, two arasin like AMPs, named as Pc-arasin1 and Pc-arasin2, were identified in red swamp crayfish Procambarus clarkii with sequence similarity to the arasins found in Hyas araneus. Both Pc-arasins consisted of signal peptide, N-terminal proline-rich region and C-terminal region containing four conserved cysteine residues. The similarity of two Pc-arasins was 44.44%, and Pc-arasin2 contained several additional residues in the N-terminus. Multiple alignment of arasin family suggested the conservation of the C-terminus and the variation of the N-terminus of Pc-arasins. Both AMPs were found hemocytes-specific, and the expression could be induced the challenge of bacteria, espeacially by the pathogenic bacterium Aeromonas hydrophila. Knockdown of each Pc-arasin expression by double strand RNA would suppress the host immunity against A. hydrophila, and the commercially synthetic Pc-arasins could rescue the knockdown consequence. Both synthetic peptide showed broad antimicrobial activity towards 3 Gram-positive bacterium and 3 Gram-negative bacterium, and the minimal inhibitory concentrations varied from 6.25 µM to 50 µM. These results presented new data about the sequence, expression and function of arasin family, and emphasized the role of this family in host immune response against bacterial pathogens. The characterization of Pc-arasins also provided potential of therapeutic agent development for disease control in aquaculture based on these two newly identified AMPs.
Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/imunologia , Astacoidea/genética , Astacoidea/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , DNA , Perfilação da Expressão Gênica , Filogenia , RNA , Alinhamento de SequênciaRESUMO
Spectrometrically or optically encoded microsphere based suspension array technology (SAT) is applicable to the high-throughput, simultaneous detection of multiple analytes within a small, single sample volume. Thanks to the rapid development of nanotechnology, tremendous progress has been made in the multiplexed detecting capability, sensitivity, and photostability of suspension arrays. In this review, we first focus on the current stock of nanoparticle-based barcodes as well as the manufacturing technologies required for their production. We then move on to discuss all existing barcode-based bioanalysis patterns, including the various labels used in suspension arrays, label-free platforms, signal amplification methods, and fluorescence resonance energy transfer (FRET)-based platforms. We then introduce automatic platforms for suspension arrays that use superparamagnetic nanoparticle-based microspheres. Finally, we summarize the current challenges and their proposed solutions, which are centered on improving encoding capacities, alternative probe possibilities, nonspecificity suppression, directional immobilization, and "point of care" platforms. Throughout this review, we aim to provide a comprehensive guide for the design of suspension arrays, with the goal of improving their performance in areas such as multiplexing capacity, throughput, sensitivity, and cost effectiveness. We hope that our summary on the state-of-the-art development of these arrays, our commentary on future challenges, and some proposed avenues for further advances will help drive the development of suspension array technology and its related fields.