RESUMEN
Exceptional points (EPs) in non-Hermitian systems have turned out to be at the origin of many intriguing effects with no counterparts in Hermitian cases. A typically interesting behavior is the chiral mode switching by dynamically winding the EP. Most encircling protocols focus on the two-state or parity-time (PT) symmetry systems. Here, we propose and investigate the dynamical encircling of multiple EPs in an anti-PT-symmetric system, which is constructed based on a one-dimensional lattice with staggered lossy modulation. We reveal that dynamically encircling the multiple EPs results in the chiral dynamics via multiple non-Hermiticity-induced nonadiabatic transitions, where the output state is always on the lowest-loss energy sheet. Compared with the PT-symmetric systems that require complicated variation of the gain/loss rate or on-site potentials, our system only requires modulations of the couplings which can be readily realized in various experimental platforms. Our scheme provides a route to study non-Hermitian physics by engineering the EPs and implement novel photonic devices with unconventional functions.
RESUMEN
BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients harboring neurotrophin receptor kinase (NTRK) family mutations remains obscure. METHODS: The Zehir cohort from cBioPortal was used to analyze the mutations (MT) frequency of NTRK family in patients with NSCLC, and their correlation with clinical characteristics and patient survival. The influence of NTRK MT on ICIs efficacy was evaluated in ICIs-treated patients from Samstein cohort and further validated by use of data from OAK/POPLAR cohort. RESULTS: In the Zehir cohort, a significant difference was observed in median overall survival (mOS) between patients with NTRK MT and wild-type (WT) (mOS: 18.97 vs. 21.27 months, HR = 1.34, 95%CI 1.00-1.78; log-rank P = 0.047). In Samstein cohort, the mOS of NTRK mutant patients receiving ICIs has improved compared to WT patients (mOS: 21.00 vs. 11.00 months, log-rank P = 0.103). Notably, in subgroup analysis, ICIs significantly prolonged mOS in patients with NTRK3 MT than in WT patients (mOS: not available vs. 11.00 months, HR = 0.36, 95%CI 0.16-0.81; log-rank P = 0.009). Identical mOS between NTRK MT and WT patients receiving ICIs treatment (mOS: 13.24 vs. 13.50 months, log-rank P = 0.775) was observed in OAK/POPLAR cohort. Moreover, a similar programmed death ligand 1 (PD-L1) expression, but higher tumor mutational burden (TMB), blood TMB (bTMB) and enriched anti-tumor immunity were observed in NTRK MT compared to WT (P < 0.05). CONCLUSION: Taking high TMB or bTMB into consideration, patients with NTRK mutant NSCLC could benefit from ICIs treatment.
Asunto(s)
Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Mutación , Biomarcadores de Tumor/genéticaRESUMEN
Increasing evidence indicates that neutrophil-associated prognostic markers, such as, tumor-associated neutrophils (TANs), neutrophil-to-T cell ratio (NTR) and neutrophil-to-lymphocyte ratio (NLR), are strongly correlated with the survival of patients with non-small cell lung cancer (NSCLC). However, either the association or the difference in their predictive efficacies remains unknown. To this aim, we investigated the influence of intratumoural TANs and peripheral NLR on the clinical outcome of NSCLC patients using tumor tissues, peripheral blood indexes, and clinicopathological data of 133 patients diagnosed with NSCLC. Additionally, Kendall correlation analysis was performed to identify the association between TANs and NLR. Our results revealed that intratumoural TANs were effective prognostic factors for favorable overall survival (OS), but were not associated with disease-free survival (DFS) in the subgroup analysis of 84 postoperative patients and progression-free survival (PFS) in 49 non-resectable NSCLC patients. Elevated NTR also indicated favorable prognosis, with high intratumoural NTR being correlated with prolonged OS and high stromal NTR being correlated with prolonged DFS. In contrast, peripheral NLR predicted dismal OS and DFS of patients receiving curative surgery. Furthermore, neither intratumoural nor stromal TANs were found to be associated with NLR, indicating that they were independent inflammatory indexes in predicting the prognosis of NSCLC. In conclusion, we discovered that TANs and NLR independently and oppositely predicted the clinical outcome of NSCLC patients, providing new sights on the role of neutrophil in tumor biology and survival prediction.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Linfocitos/patología , Neutrófilos/patología , Estudios RetrospectivosRESUMEN
MicroRNAs are considered to play important roles in cell biological and pathological progress. microRNA-206 (miR-206) was reported to participate in lipogenesis, and lipid droplets were necessary for the life cycle of HCV proliferation. Whether miR-206 was associated with HCV proliferation and the potential mechanism are not clear. In this study, we firstly identified that miR-206 could inhibit HCV proliferation at the RNA and protein level. Bioinformatical prediction of target genes binding to miR-206 was performed to investigate whether inhibiting function was due to a lipogenesis pathway. Then, the acetyl-CoA carboxylase 1 (ACC1) gene was selected as target gene of miR-206. The dual-luciferase reporter assay results showed that luciferase significantly decreased in cells transfected with 3'-UTR of the ACC1 gene and miR-206. The RNA and protein levels of the ACC1 gene and its pathway genes were significantly lower in cells transfected with miR-206 than in controls. Furthermore, the lipid droplet numbers also significantly decreased in cells transfected with miR-206. In conclusion, miR-206 could inhibit HCV proliferation through depressing ACC1 lipogenesis pathway and decreasing the lipid droplet numbers. miR-206 might be used as anti-HCV biochemical drug in the future.
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Acetiltransferasas , Hepacivirus , Metabolismo de los Lípidos , MicroARNs , Replicación Viral , Regiones no Traducidas 3' , Acetiltransferasas/genética , Acetiltransferasas/metabolismo , Línea Celular Tumoral , Hepacivirus/genética , Hepacivirus/metabolismo , Humanos , Metabolismo de los Lípidos/genética , Lípidos/biosíntesis , Lípidos/genética , Luciferasas/genética , Luciferasas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Transducción de Señal , Replicación Viral/genética , Replicación Viral/fisiologíaRESUMEN
Melatonin improves plant resistance to multiple stresses by participating in the biosynthesis of metabolites. Flavonoids are an important family of plant secondary metabolites and are widely recognized to be involved in resistance; however, the crosstalk between melatonin and flavonoid is largely unknown. We found that the resistance of pigeon pea (Cajanus cajan) to salt, drought, and heat stresses were significantly enhanced by pre-treatment with melatonin. Combined transcriptome and LC-ESI-MS/MS metabolomics analyses showed that melatonin significantly induced the enrichment of flavonoids and mediated the reprogramming of biosynthetic pathway genes. The highest fold-increase in expression in response to melatonin treatment was observed for the CcF3´H family, which encodes an enzyme that catalyses the biosynthesis of luteolin, and the transcription factor CcPCL1 directly bonded to the CcF3´H-5 promoter to enhance its expression. In addition, salt stress also induced the expression of CcPCL1 and CcF3´H-5, and their overexpression in transgenic plants greatly enhanced salt tolerance by promoting the biosynthesis of luteolin. Overall, our results indicated that pre-treatment of pigeon pea with melatonin promoted luteolin biosynthesis through the CcPCL1 and CcF3´H-5 pathways, resulting in salt tolerance. Our study shows that melatonin enhances plant tolerance to multiple stresses by mediating flavonoid biosynthesis, providing new avenues for studying the crosstalk between melatonin and flavonoids.
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Cajanus , Melatonina , Cajanus/genética , Flavonoides , Regulación de la Expresión Génica de las Plantas , Luteolina/farmacología , Melatonina/metabolismo , Melatonina/farmacología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Estrés Salino , Espectrometría de Masas en Tándem , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Dysbiosis or imbalance of gut microbiota in Alzheimer's disease (AD) affects the production of short-chain fatty acids (SCFAs), whereas exogenous SCFAs supplementation exacerbates brain Aß burden in APP/PS1 mice. Bifidobacterium is the main producer of SCFAs in the gut flora, but oral administration of Bifidobacterium is ineffective due to strong acids and bile salts in the gastrointestinal tract. Therefore, regulating the levels of SCFAs in the gut is of great significance for AD treatment. METHODS: We investigated the feasibility of intranasal delivery of MSNs-Bifidobacterium (MSNs-Bi) to the gut and their effect on behavior and brain pathology in APP/PS1 mice. RESULTS: Mesoporous silica nanospheres (MSNs) were efficiently immobilized on the surface of Bifidobacterium. After intranasal administration, fluorescence imaging of MSNs-Bi in the abdominal cavity and gastrointestinal tract revealed that intranasally delivered MSNs-Bi could be transported through the brain to the peripheral intestine. Intranasal administration of MSNs-Bi not only inhibited intestinal inflammation and reduced brain Aß burden but also improved olfactory sensitivity in APP/PS1 mice. CONCLUSIONS: These findings suggested that restoring the balance of the gut microbiome contributes to ameliorating cognitive impairment in AD, and that intranasal administration of MSNs-Bi may be an effective therapeutic strategy for the prevention of AD and intestinal disease.
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Enfermedad de Alzheimer , Nanopartículas , Trastornos del Olfato , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Animales , Bifidobacterium/metabolismo , Ácidos y Sales Biliares , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Ácidos Grasos Volátiles , Ratones , Ratones Transgénicos , Trastornos del Olfato/patología , Dióxido de SilicioRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICIs) have been shown to significantly improve the survival of patients with advanced lung adenocarcinoma (LUAD). However, only limited proportion of patients could benefit from ICIs. Novel biomarkers with strong predictability are needed for clinicians to maximize the efficacy of ICIs. Our study aimed to identify potential biomarkers predicting ICIs efficacy in LUAD. METHODS: The Cancer Genome Atlas (TCGA) PanCancer Atlas studies in cBioportal were used to evaluate the mutation frequency of ANK2 across multiple cancers. Clinical and mutational data for LUAD from ICIs-treated cohorts (Hellmann et al. and Rizvi et al.) were collected to explore the correlation between ANK2 mutation and clinical outcomes. In addition, the relationship between ANK2 expression and clinical outcomes was analyzed using LUAD data from TCGA and Gene Expression Omnibus. Furthermore, the impact of ANK2 mutation and expression on the tumor immune microenvironment of LUAD was analyzed using TCGA and TISIDB databases. RESULTS: Patients with ANK2 mutation benefited more from ICIs. In ICIs-treated cohort, prolonged progression-free survival (PFS) (median PFS: NR (not reached) vs. 5.42 months, HR (hazard ratio) 0.31, 95% CI 0.18-0.54; P = 0.0037), improved complete response rate (17.65% vs. 1.85%, P = 0.0402), and improved objective response rate (64.71% vs. 24.07%, P = 0.0033) were observed in LUAD patients with ANK2 mutation compared to their wild-type counterparts. Regarding ANK2 expression, it was observed that ANK2 expression was decreased in LUAD (P < 0.05) and a higher level of ANK2 expression was associated with longer overall survival (HR 0.69, 95% CI 0.52-0.92; P = 0.012) in TCGA LUAD cohort. Moreover, ANK2 mutation or higher ANK2 expression correlated with enhanced antitumor immunity and "hot" tumor microenvironment in LUAD, which could be potential mechanisms that ANK2 mutation facilitated ICIs therapy and patients with higher ANK2 expression survived longer. CONCLUSION: Our findings suggest that ANK2 mutation or increased ANK2 expression may serve as a favorable biomarker for the efficacy of ICIs in patients with LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Biomarcadores , Bases de Datos Factuales , Mutación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Biomarcadores de Tumor/genética , Microambiente Tumoral , Ancirinas/genéticaRESUMEN
Conductive and porous nitrogen-rich materials have great potential as supercapacitor electrode materials. The exceptional efficiency of such compounds, however, is dependent on their larger surface area and the level of nitrogen doping. To address these issues, we synthesized a porous covalent triazine framework (An-CTFs) based on 9,10-dicyanoanthracene (An-CN) units through an ionothermal reaction in the presence of different molar ratios of molten zinc chloride (ZnCl2) at 400 and 500 °C, yielding An-CTF-10-400, An-CTF-20-400, An-CTF-10-500, and An-CTF-20-500 microporous materials. According to N2 adsorption-desorption analyses (BET), these An-CTFs produced exceptionally high specific surface areas ranging from 406-751 m2·g-1. Furthermore, An-CTF-10-500 had a capacitance of 589 F·g-1, remarkable cycle stability up to 5000 cycles, up to 95% capacity retention, and strong CO2 adsorption capacity up to 5.65 mmol·g-1 at 273 K. As a result, our An-CTFs are a good alternative for both electrochemical energy storage and CO2 uptake.
Asunto(s)
Estructuras Metalorgánicas , Triazinas , Adsorción , Antracenos , Dióxido de Carbono/química , Nitrógeno/química , Triazinas/químicaRESUMEN
Systemic chemotherapy is still the primary treatment for advanced-stage nasopharyngeal carcinoma (NPC), but only limited therapeutic success has been achieved in the past decade because of drug resistance and systemic toxicity. Curcumin (Cur) is an effective alternative to chemotherapeutics because it showed remarkable therapeutic potential in the treatment of NPC. However, lack of tissue specificity and poor penetration in solid tumors are the major obstacles to effective therapy. Therefore, in this work, a self-assembled sub-30 nm therapeutic lipid nanoparticle loaded with Cur, named as Cur@α-NTP-LN, was constructed, specifically targeting scavenger receptor class B member 1 (SR-B1) and enhancing its therapeutic effects on NPC in vivo. Our results showed that Cur@α-NTP-LNs were effective and superior to free Cur on NPC cell-specific targeting, suppressing cell proliferation and inducing cell apoptosis. In vivo and ex vivo optical imaging revealed that Cur@α-NTP-LNs exerted high targeting efficiency, specifically accumulating in NPC xenograft tumors and delivering Cur into the tumor center after systemic administration. Furthermore, Cur@α-NTP-LNs exhibited a remarkable inhibitory effect on the growth of NPC subcutaneous tumors, with over 71 and 47% inhibition compared to Cur- and α-NTP-LNs-treated groups, respectively. In addition, Cur@α-NTP-LNs almost blocked NPC metastasis in a lung metastasis model of NPC and significantly improved the survival rate. Thus, the sub-30 nm Cur@α-NTP-LNs enhanced the solubility of Cur and demonstrated the ability of targeted Cur delivery into the center of the solid NPC tumor, performing synergistic inhibitory effects on the growth of NPC tumor and its metastasis with high efficiency.
Asunto(s)
Curcumina/farmacología , Portadores de Fármacos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Liposomas/farmacología , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Administración Cutánea , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Neoplasias Pulmonares , Ratones , Nanopartículas , Metástasis de la Neoplasia , Tamaño de la Partícula , Péptidos , SolubilidadRESUMEN
A method of ultra-fast liquid chromatography in series with tandem mass spectrometry for the rapid and sensitive detection of 57 compounds in Spatholobi Caulis (the vine stem of Spatholobus suberectus Dunn) within 35 min was established. This assay can simultaneously determine a variety of compounds without matrix interference in multiple reaction monitoring mode including evaluating the quality of different batches of Spatholobi Caulis from several areas and further identifying the characteristic compounds efficiently. After comprehensive validation, this method can be used to determinate samples rapidly, precisely, accurately, repeatably, and sensitivity. There were significant content differences in 12 batches of Spatholobi Caulis, which were further classified and systematically differentiated applying multivariate statistical analysis. Furthermore, orthogonal partial least squares discrimination analysis results indicated that (-)-gallocatechin (10), (-)-epiafzelechin (20), 4,7,2'-trihydroxy-4'-methoxyisoflavanol (51), and biochanin A (53) characterize compounds to discernment internal quality of Spatholobi Caulis, and recommended as quality control indicators. Hence, presented work provides a method for further study on pharmaceutic preparation, metabolism, as well as for the design, production optimization process, and clinical application.
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Medicamentos Herbarios Chinos/análisis , Fabaceae/química , Extractos Vegetales/análisis , Cromatografía Líquida de Alta Presión , Estructura Molecular , Espectrometría de Masas en TándemRESUMEN
Five biochars derived from lotus seedpod (LSP) were applied to examine and compare the adsorption capacity of 17ß-estradiol (E2) from aqueous solution. The effect of KOH activation and the order of activation steps on material properties were discussed. The effect of contact time, initial concentration, pH, ionic strength and humic acid on E2 adsorption were investigated in a batch adsorption process. Experimental results demonstrated that the pseudo second-order model fitted the experimental data best and that adsorption equilibrium was reached within 20â¯hr. The efficiency of E2 removal increased with increasing E2 concentration and decreased with the increase of ionic strength. E2 adsorption on LSP-derived biochar (BCs) was influenced little by humic acid, and slightly affected by the solution pH when its value ranged from 4.0 to 9.0, but considerably affected at pHâ¯10.0. Low environmental temperature is favorable for E2 adsorption. Chemisorption, π-π interactions, monolayer adsorption and electrostatic interaction are the possible adsorption mechanisms. Comparative studies indicated that KOH activation and the order of activation steps had significant impacts on the material. Post-treated biochar exhibited better adsorption capacity for E2 than direct treated, pre-treated, and raw LSP biochar. Pyrolyzed biochar at higher temperature improved E2 removal. The excellent performance of BCs in removing E2 suggested that BCs have potential in E2 treatment and that the biochar directly treated by KOH would be a good choice for the treatment of E2 in aqueous solution, with its advantages of good efficiency and simple technology.
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Estradiol/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Adsorción , Carbón Orgánico , Calor , Sustancias Húmicas , Concentración de Iones de Hidrógeno , Hidróxidos , Cinética , Lotus , Concentración Osmolar , Compuestos de Potasio , Semillas , TemperaturaRESUMEN
The chemical compounds in water extract of Spatholobi Caulis were further studied. The compounds were systematically isolated and purified by using various separation and analysis techniques including silica gel, macroporous adsorptive resins and Sephadex LH-20 column chromatographies, as well as reversed phase high-performance liquid chromatography(RP-HPLC). Twenty-three flavonoids and one chromone were identified by the spectroscopic analysis techniques combining their physicochemical properties, they were identified as isoduartin(1), sativan(2), 8-O-methylretusin(3), 7-hydroxydihydroflavone(4), odoratin(5), butesuperin A(6), biochanin A(7), 3'-methoxydaidzein(8), 7-hydroxychromone(9), calycosin(10), naringenin(11), dihydrocajanin(12),(6 aR,11 aR)-maackiain(13), 2'-hydroxygenistein(14),(6 aR,11 aR)-medicarpin-3-O-glucopyranoside(15),(-)-epiafzelechin(16),(-)-catechin(17),(-)-epicatechin(18), 4',8-dimethoxy-7-O-ß-D-glucopyranosylisoflavone(19), ononin(20),(-)-gallocatechin(21), rutin(22), daidzin(23) and sphaerobioside(24). Compounds 4, 6, 8, 9, 11, 12, 14-16, 19 and 22-24 were isolated from Spatholobi Caulis for the first time.
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Medicamentos Herbarios Chinos/química , Fabaceae/química , Flavonoides/química , Fitoquímicos/química , Cromatografía Líquida de Alta Presión , Flavonoides/aislamiento & purificación , Fitoquímicos/aislamiento & purificaciónRESUMEN
To study the non-flavonoids chemical constituents in water extract of Spatholobi Caulis. Some purification and analysis techniques like silica gel, D101-macroporous adsorptive resins, and Sephadex LH-20 column chromatographies as well as reversed phase high-performance liquid chromatography were used to isolate and analyze the phenolic acid esters and other type compounds from Spatholobi Caulis integrally. The structures of these compounds were identified by spectroscopic techniques such as nuclear magnetic resonance and high resolution mass spectrometries. Twenty-seven compounds, including phenolic acid, coumarin, lignan, terpene, alkaloid, and steroid compounds, were isolated from ethyl acetate and n-butanol fractions in water extract of Spatholobi Caulis, and they were identified as ß-sitosterol(1), feruli acid methyl ester(2), syringaresinol(3),(+)-medioresinol(4),(+)-epipinoresinol(5), p-acetylphenol(6), bolusanthin â £(7), evofolin B(8), salicylic acid(9), trans-p-hydroxy-cinnamic acid(10), abscisic acid(11), m-hydroxyphenol(12), C-veratroylglycol(13), p-hydroquinone(14), 8,9-dihydroxymegastigma-4,6-dien-3-one(15), p-hydroxybenzoic acid(16), 6,9-dihydroxymegastigma-4,7-dien-3-one(17), protocatechuic acid(18), protocatechuic acid methyl ester(19), 5,7-dihydroxycoumarin(20), isolariciresinol(21), nicotinic acid(22), daucosterol(23),(+)-pinoresinol(24), stigmasterol(25), allantoin(26) and koaburaside(27), respectively. Furthermore, compounds 2-15, 19-22, 24 and 26 were isolated from genus Spatholobus for the first time.
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Medicamentos Herbarios Chinos/análisis , Fabaceae/química , Fitoquímicos/análisis , Ésteres/análisis , Hidroxibenzoatos/análisis , Espectrometría de MasasRESUMEN
The dried vine stems of Spatholobus suberectus are commonly used in traditional Chinese medicine for treating gynecological and cardiovascular diseases. In this study, five new compounds named spasuberol A (2), homovanillyl-4-oxo-nonanoate (5), spasuberol C (6), spasuberoside A (14), and spasuberoside B (15), together with ten known compounds (1, 3, 4, 7-13), were isolated from the dried vine stems of S. suberectus. Their chemical structures were analyzed using spectroscopic assays. This is the first study interpreting the detailed structural information of 4. The anti-inflammatory activity of these compounds was evaluated by reducing nitric oxide overproduction in RAW264.7 macrophages stimulated by lipopolysaccharide. Compounds 1 and 8-10 showed strong inhibitory activity with half maximal inhibitory concentration (IC50) values of 5.69, 16.34, 16.87, and 6.78 µM, respectively, exhibiting higher activity than the positive drug l-N6-(1-iminoethyl)-lysine (l-NIL) with an IC50 value of 19.08 µM. The IC50 values of inhibitory activity of compounds 2 and 4-6 were 46.26, 40.05, 45.87, and 28.29 µM respectively, which were lower than l-NIL, but better than that of positive drug indomethacin with an IC50 value of 55.44 µM. Quantitative real-time polymerase chain reaction analysis revealed that assayed compounds with good anti-inflammatory activity, such as 1, 6, 9, and 10 at different concentrations, can reduce the messenger RNA (mRNA) expression of some pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). The anti-inflammatory activity and the possible mechanism of the compounds mentioned in this paper were studied preliminarily.
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Antiinflamatorios/farmacología , Fabaceae/química , Expresión Génica/efectos de los fármacos , Glicósidos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Óxido Nítrico/antagonistas & inhibidores , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Glicósidos/química , Glicósidos/aislamiento & purificación , Humanos , Indometacina/farmacología , Concentración 50 Inhibidora , Lipopolisacáridos/farmacología , Lisina/análogos & derivados , Lisina/farmacología , Medicina Tradicional China , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/química , Tallos de la Planta/química , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To explore the genetic basis for a patient with autism. METHODS: High-throughput sequencing was carried out to detect copy number variations in the patient. RESULTS: DNA sequencing found that the patient has carried a 0.11 Mb deletion in distal 2p16.3 spanning from genomic position 50 820 001 to 50 922 000, which resulted removal of exon 6 and part of intron 7 of the NRXN1 gene. The same deletion was not found his parents and brother. CONCLUSION: Partial deletion of the NRXN1 gene may underlie the disease in this patient.
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Trastorno Autístico/genética , Moléculas de Adhesión Celular Neuronal/genética , Eliminación de Gen , Proteínas del Tejido Nervioso/genética , Proteínas de Unión al Calcio , Variaciones en el Número de Copia de ADN , Humanos , Masculino , Moléculas de Adhesión de Célula NerviosaRESUMEN
To establish an HPLC characteristic fingerprint method of Fuke Qianjin Capsules,and determine the contents of its main components. The analysis was carried out on a Kromasil 100-5-C18 analytical column(4. 6 mm ×250 mm,5 µm) with gradient elution by acetonitrile(A)-0. 1% phosphoric acid aqueous solution(B),a flow rate at 1. 0 m L·min-1 and the detection wavelength of 254 nm.The column temperature was 30 â,and the injection volume was 10 µL. The determination method of genistin,jatrorrhizine,andrographolide and 14-deoxy-11,12-didehydroandrographolide index components were studied methodologically. The common mode of the characteristic fingerprint of Fuke Qianjin Capsules was set up with 8 common peaks,which were identified as genistin,jatrorrhizine,palmatine,berberine,andrographolide,14-deoxy-11,12-didehydroandrographolide,Z-ligustilide,and Z-3-butylidenephthalide,respectively,in comparison with the references. The similarities of 20 batches of Fuke Qianjin Capsules samples were above 0. 95. All of the above-mentioned 4 analytes could be well separated under the optimized chromatographic conditions. RSD of precision and repeatability experiment were both less than 1. 5%,and the sample solution was stable during 72 h. All of the compounds had a good linearity and linear range. The contents of genistin,jatrorrhizine,andrographolide,and 14-deoxy-11,12-didehydroandrographolide in 20 batches of Fuke Qianjin Capsules samples were 28. 66-56. 04,94. 77-197. 92,1 705. 33-4 148. 93 and 462. 16-1 225. 96 µg in each capsule,respectively. The developed HPLC characteristic fingerprint and quantitative analysis methods were reliable,accurate and sensitive,and could be used effectively evaluate the quality of Fuke Qianjin Capsules samples.
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Medicamentos Herbarios Chinos/química , Fitoquímicos/análisis , Cápsulas , Cromatografía Líquida de Alta PresiónRESUMEN
BACKGROUND: TSP50 (testes-specific protease 50) has been reported to be a candidate oncogene and is overexpressed in various cancers. Our previous study demonstrated that TSP50 protein is elevated in gastric cancer, and its high expression is associated with unfavorable prognosis and lymph node metastasis. However, the role of TSP50 in gastric cancer remains elusive. METHODS: qRT-PCR, western blot were used to determine TSP50 expression in gastric cancer cell lines. Role of TSP50 in proliferation and invasion was examined by BrdU incorporation assay, cell count, wound healing and transwell assay. Immunohistochemistry and western blot were performed to identify the potential mechanisms involved. RESULTS: TSP50 was highly expressed in most of the gastric cancer cell lines at both mRNA and protein levels. Up-regulation of TSP50 in gastric cancer cells enhanced proliferation and invasiveness, whereas down-regulation of TSP50 by its specific shRNA decreased it. A negative correlation between TSP50 and E-Cadherin was found in gastric cancer tissues, and combination of them improves the prediction for prognosis and lymph node metastasis. Mechanistic studies revealed that overexpression of TSP50 increased the expression of epithelial-to-mesenchymal transition (EMT) markers including Vimentin, and Twist, and decreased the epithelial marker E-Cadherin. NF-κB signaling pathway is involved in the regulatory effects of TSP50 on EMT, migration and invasion in gastric cancer cells. CONCLUSION: TSP50 promotes the proliferation, migration and invasion of gastric cancer cells involving NF-κB dependent EMT activation. Targeting TSP50 may provide a novel therapeutic strategy for the management of gastric cancer.
Asunto(s)
Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Serina Endopeptidasas/genética , Neoplasias Gástricas/genética , Cadherinas/genética , Movimiento Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , FN-kappa B/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Neoplasias Gástricas/patología , Testículo/metabolismoRESUMEN
Background: Gastric cancer is one of the most common cancers and is the second leading cause of cancer mortality worldwide. The present study aimed to investigate the potential biological effect of long non-coding RNA (lncRNA) BNC2-AS1 on the proliferation, migration, and invasion of cervical cancer cells. Methods: BNC2-AS1 small interfering RNA (siRNA) was transfected into SGC7901 and BGC823 gastric cancer cell lines, with negative siRNA serving as a control. A reverse transcription-quantitative polymerase chain reaction assay was performed to confirm the knockdown of BNC2-AS1. Cell Counting Kit (CCK)-8 and colony-forming unit (CFU) assays were performed to evaluate the effect of BNC2-AS1-knockdown on SGC7901 and BGC823 cell proliferation. A wound healing assay was performed to evaluate the effect of BNC2-AS1-knockdown on SGC7901 and BGC823 cell proliferation and migration. A tumor invasion assay was used to evaluate the effect of BNC2-AS1-knockdown on SGC7901 and BGC823 cell invasion. The expression level of BNC2-AS1 was efficiently knocked down by siRNA 48 hours post-transfection. Results: The results of CCK8 and CFU assays showed that BNC2-AS1-knockdown significantly decreased gastric cancer cell proliferation. Wound healing assay results indicated that BNC2-AS1-knockdown markedly suppressed gastric cancer cell proliferation and migration. Tumor invasion assay results demonstrated that BNC2-AS1-knockdown significantly suppressed gastric cancer cell invasion. Conclusions: BNC2-AS1 levels in gastric cancer SGC7901 and BGC823 cell lines can be efficiently knocked down using the siRNA strategy, and the BNC2-AS1 knockdown can significantly suppress the tumor characteristics of gastric cancer cells, including the ability of proliferation, migration, and invasion.
Asunto(s)
Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , Neoplasias Gástricas/genética , Línea Celular Tumoral , Humanos , Invasividad Neoplásica , Interferencia de ARN , Neoplasias Gástricas/patología , TransfecciónRESUMEN
Most digestive system tumors have poor prognoses due to the lack of specific biomarkers. Circular RNAs (circRNAs) regulate the expression of genes and play essential roles in digestive system tumorigenesis. Here we review circRNA functions in gastrointestinal tract tumors. CircRNAs are promising biomarkers for clinical applications for gastrointestinal tract tumors.