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1.
Environ Sci Technol ; 58(1): 739-750, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38147428

RESUMEN

Understanding the reaction mechanism of dissolved organic matter (DOM) during wastewater biotreatment is crucial for optimal DOM control. Here, we develop a directed paired mass distance (dPMD) method that constructs a molecular network displaying the reaction pathways of DOM. It couples direction inference and PMD analysis to extract the substrate-product relationships and delta masses of potentially paired reactants directly from sequential mass spectrometry data without formula assignment. Using this method, we analyze the influent and effluent samples from the bioprocesses of 12 wastewater treatment plants (WWTPs) and build a dPMD network to characterize the core reactome of DOM. The network shows that the first step of the transformation triggers reaction cascades that diversify the DOM, but the highly overlapped subsequent reaction pathways result in similar effluent DOM compositions across WWTPs despite varied influents. Mass changes exhibit consistent gain/loss preferences (e.g., +3.995 and -16.031) but different occurrences across WWTPs. Combined with genome-centric metatranscriptomics, we reveal the associations among dPMDs, enzymes, and microbes. Most enzymes are involved in oxygenation, (de)hydrogenation, demethylation, and hydration-related reactions but with different target substrates and expressed by various taxa, as exemplified by Proteobacteria, Actinobacteria, and Nitrospirae. Therefore, a functionally diverse community is pivotal for advanced DOM degradation.


Asunto(s)
Materia Orgánica Disuelta , Purificación del Agua , Aguas Residuales , Bacterias
2.
Mikrochim Acta ; 190(5): 186, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-37071204

RESUMEN

To meet high-throughput screening of the residues of sulfonamides (SAs) with high sensitivity toward sulfamethazine (SM2) in milk samples, a new highly sensitive lateral flow immunoassay (LFA) based on amorphous carbon nanoparticles (ACNs) was developed. First, a group-specific monoclonal antibody 10H7 (mAb 10H7) that could recognize 25 SAs with high sensitivity toward SM2 (IC50 value of 0.18 ng/mL) was prepared based on H1 as an immune hapten and H4 as a heterologous coating hapten. Then, mAb 10H7 was conjugated to ACNs as an immune probe for LFA development. Under the optimized conditions, the LFA could detect 25 SAs with the cut-off value toward SM2 of 2 ng/mL, which could meet the requirement for detection of SAs. In addition, the LFA developed was also used for screening SAs' residues in real milk samples, with results being consistent with HPLC-MS/MS. Thus, this LFA can be used as a high-throughput screening tool for detection of SAs.


Asunto(s)
Anticuerpos Monoclonales , Nanopartículas , Animales , Leche/química , Sulfonamidas/análisis , Espectrometría de Masas en Tándem , Inmunoensayo/métodos , Sulfanilamida/análisis , Haptenos , Carbono
3.
Molecules ; 28(15)2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37570682

RESUMEN

The purpose of this study was to evaluate L-cysteine-modified transfersomes as the topical carrier for enhanced epidermal delivery of podophyllotoxin (POD). L-cysteine-deoxycholic acid (LC-DCA) conjugate was synthesized via an amidation reaction. POD-loaded L-cysteine-modified transfersomes (POD-LCTs) were prepared via a thin membrane dispersion method and characterized for their particle size, zeta potential, morphology, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and in vitro release. Subsequently, in vitro skin permeation and retention, fluorescence distribution in the skin, hematoxylin-eosin staining and in vivo skin irritation were studied. The POD-LCTs formed spherical shapes with a particle size of 172.5 ± 67.2 nm and a zeta potential of -31.3 ± 6.7 mV. Compared with the POD-Ts, the POD-LCTs provided significantly lower drug penetration through the porcine ear skin and significantly increased the skin retention (p < 0.05). Meaningfully, unlike the extensive distribution of the POD-loaded transfersomes (POD-Ts) throughout the skin tissue, the POD-LCTs were mainly located in the epidermis. Moreover, the POD-LCTs did not induce skin irritation. Therefore, the POD-LCTs provided an enhanced epidermal delivery and might be a promising carrier for the topical delivery of POD.


Asunto(s)
Cisteína , Podofilotoxina , Animales , Porcinos , Administración Cutánea , Podofilotoxina/farmacología , Piel , Epidermis , Tamaño de la Partícula , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos
4.
Respirology ; 27(10): 844-853, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35705329

RESUMEN

BACKGROUND AND OBJECTIVE: Single-study evidence of separate and combined effectiveness of influenza and pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To fill this gap, we studied the effectiveness of trivalent seasonal influenza vaccine (TIV) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately and together, at preventing adverse COPD outcomes. METHODS: Our study used a self-controlled, before-and-after cohort design to assess the effectiveness of TIV and PPSV23 in COPD patients. Patients were recruited from hospitals in Tangshan City, Hebei Province, China. Subjects self-selected into one of the three vaccination schedules: TIV group, PPSV23 group and TIV&PPSV23 group. We used a physician-completed, medical record-verified questionnaire to obtain data on acute exacerbations of COPD (AECOPD), pneumonia and related hospitalization. Vaccine effectiveness was determined by comparing COPD outcomes before and after vaccination, controlling for potential confounding using Cox regression. RESULTS: We recruited 474 COPD patients, of whom 109 received TIV, 69 received PPSV23 and 296 received TIV and PPSV23. Overall effectiveness for preventing AECOPD, pneumonia and related hospitalization were respectively 70%, 59% and 58% in the TIV group; 54%, 53% and 46% in the PPSV23 group; and 72%, 73% and 69% in the TIV&PPSV23 group. The vaccine effectiveness without COVID-19 non-pharmaceutical intervention period were 84%, 77% and 88% in the TIV group; 63%, 74% and 66% in the PPSV23 group; and 82%, 83% and 91% in the TIV&PPSV23 group. CONCLUSION: Influenza vaccination and PPSV23 vaccination, separately and together, can effectively reduce the risk of AECOPD, pneumonia and related hospitalization. Effectiveness for preventing AECOPD was the greatest.


Asunto(s)
COVID-19 , Vacunas contra la Influenza , Gripe Humana , Infecciones Neumocócicas , Neumonía Neumocócica , Neumonía , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Infecciones Neumocócicas/inducido químicamente , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Neumonía/inducido químicamente , Neumonía Neumocócica/epidemiología , Neumonía Neumocócica/prevención & control , Enfermedad Pulmonar Obstructiva Crónica/complicaciones
5.
J Environ Sci (China) ; 116: 220-228, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35219420

RESUMEN

The characteristics of dissolved organic matter (DOM) can significantly affect the degradation of target compounds by the advanced oxidation processes. In this study, the effects of the different hydrophobicity/hydrophilicity fractions, molecular weight (MW) fractions, fluorescence components and molecular components of DOM extracted from municipal wastewater on the degradation of 4 pharmaceutically active compounds (PhACs), including carbamazepine, clofibric acid, atenolol and erythromycin by the UV/H2O2 process were investigated. The results showed that the degradation rate constants of 4 PhACs decreased dramatically in the presence of DOM. The linear regressions of 4 PhACs degradation as a function of specific fluorescence intensity (SFI) are exhibited during the degradation of 4 PhACs and the SFI may be used to evaluate effect of DOM on target compounds in wastewater. The hydrophobic acid (HPO-A) exhibited the strongest inhibitory effect on degradation of 4 PhACs during oxidation process. The small MW fractions of DOM significantly inhibited the degradation of 4 PhACs during oxidation process. Among three fluorescence components, hydrophobic humic-like substances may significantly inhibit the degradation of 4 PhACs during oxidation process. At the molecular level, the formulas may be derived from terrestrial sources. CHO compound may significantly inhibit the degradation of 4 PhACs during oxidation process on formula classes. The unsaturated hydrocarbons, carbohydrates and tannins compounds may significantly inhibit the effectiveness of the UV/H2O2 process on compound classes.


Asunto(s)
Materia Orgánica Disuelta , Aguas Residuales , Contaminantes Químicos del Agua , Peróxido de Hidrógeno , Aguas Residuales/química , Contaminantes Químicos del Agua/análisis
6.
Environ Sci Technol ; 55(9): 6227-6238, 2021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33891391

RESUMEN

Microbe-derived dissolved organic nitrogen (mDON) can readily induce harmful phytoplankton blooms, and thus, restricting its discharges is necessary. Recently, algae biofilm (AB) has attracted increasing interest for its advantages in nutrient recovery. However, its features in mDON control remain unexplored. Herein, AB's mDON formation and utilization performance, molecular characteristics, and metabolic traits have been investigated, with activated sludge (AS) as the benchmark for comparisons. Comparatively, AB reduced mDON formation by 83% when fed with DON-free wastewater. When fed with AS's effluent, it consumed at least 72% of the exogenous mDON and notably reduced the amount of protein/amino sugar-like compounds. Irrespective of the influent, AB ultimately produced more various unsaturated hydrocarbon and lignin analogues. Redundancy and network analysis highlighted the algal-bacterial synergistic effects exemplified by cross-feeding in reducing mDON concentrations and shaping mDON pools. Moreover, metagenomics-based metabolic reconstruction revealed that cyanobacteria Limnothrix and Kamptonema spp. facilitated mDON uptake, ammonification, and recycling, which supplied the extensive nitrogen assimilatory demand for amino acids, vitamins, and cofactors biosynthesis, and therefore promoted mDON scavenging. Our findings demonstrate that regardless of the secondary or tertiary process, cyanobacteria-dominated AB is promising to minimize bioavailable mDON discharges, which has implications for future eutrophication control.


Asunto(s)
Nitrógeno , Aguas Residuales , Biopelículas , Eutrofización , Nitrógeno/análisis , Aguas del Alcantarillado
7.
Environ Sci Technol ; 55(16): 11294-11307, 2021 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-34338502

RESUMEN

Understanding the degradation of dissolved organic matter (DOM) is vital for optimizing DOM control. However, the microbe-mediated DOM transformation during wastewater treatment remains poorly characterized. Here, microbes and DOM along full-scale biotreatment processes were simultaneously characterized using comparative genomics and high-resolution mass spectrometry-based reactomics. Biotreatments significantly increased DOM's aromaticity and unsaturation due to the overproduced lignin and polyphenol analogs. DOM was diversified by over five times in richness, with thousands of nitrogenous and sulfur-containing compounds generated through microbe-mediated oxidoreduction, functional group transfer, and C-N and C-S bond formation. Network analysis demonstrated microbial division of labor in DOM transformation. However, their roles were determined by their functional traits rather than taxa. Specifically, network and module hubs exhibited rapid growth potentials and broad substrate affinities but were deficient in xenobiotics-metabolism-associated genes. They were mainly correlated to liable DOM consumption and its transformation to recalcitrant compounds. In contrast, connectors and peripherals were potential degraders of recalcitrant DOM but slow in growth. They showed specialized associations with fewer DOM molecules and probably fed on metabolites of hub microbes. Thus, developing technologies (e.g., carriers) to selectively enrich peripheral degraders and consequently decouple the liable and recalcitrant DOM transformation processes may advance DOM removal.


Asunto(s)
Purificación del Agua , Genómica , Espectrometría de Masas , Nitrógeno , Oxidación-Reducción
8.
Bioorg Chem ; 116: 105340, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34530236

RESUMEN

Cancers are highly heterogeneous and typically contain a small subset of drug-resisting cells called tumor initiating cells or cancer stem cells (CSCs). CSCs can self-renew, divide asymmetrically, and often cause tumor invasion and metastasis. Therefore, treatments specifically targeting CSCs are critical to improve patient survival. Recently, we identified a highly specific peptidomimetic (peptoid - PCS2) that selectively binds to the CSC subpopulation of lung cancer over the remaining cancer cells (non-CSCs). Subsequently, we identified plectin as the target of PCS2. Plectin is an intracellular structural protein, which is involved in tumor invasion and metastasis when it appears on cell surface. While PCS2 monomer did not display any anti-cancer activity, we designed a series of homo-dimeric versions of PCS2, and identified PCS2D1.2 optimized homo-dimer that displayed highly specific cytotoxicity towards CSCs over non-CSCs. PCS2D1.2 effectively blocked the in vitro colony formation and cell migration, hallmarks of CSCs. Furthermore, PCS2D1.2 reduced the in vivo tumor formation. In both in vitro and in vivo studies, PCS2D1.2 effectively reduced plectin expression and/or plectin-rich CSCs, but had no effect on non-CSCs. Therefore, PCS2D1.2 has the potential to be developed as a highly CSC specific drug candidate, which can be used in combination with current anti-cancer drugs.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Peptidomiméticos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Estructura Molecular , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Peptidomiméticos/síntesis química , Peptidomiméticos/química , Relación Estructura-Actividad
9.
Mikrochim Acta ; 188(2): 59, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33507410

RESUMEN

A homogeneous fluorescence quenching immunoassay is described for simultaneous separation and detection of aflatoxin M1 (AFM1) in milk. The novel assay relies on monoclonal antibody (mAb) functionalized Fe3O4 decorated reduced-graphene oxide (rGO-Fe3O4-mAb) as both capture probe and energy acceptor, combined with tetramethylrhodamine cadaverine-labeled aflatoxin B1 (AFB1-TRCA) as the energy donor. In the assay, AFB1-TRCA binds to rGO-Fe3O4-mAb in the absence of AFM1, quenching the fluorescence of TRCA by resonance energy transfer. Significantly, the immunoassay integrates sample preparation and detection into a single step, by using magnetic graphene composites to avoid washing and centrifugation steps, and the assay can be completed within 10 min. Under optimized conditions, the visual and quantitative detection limits of the assay for AFM1 were 50 and 3.8 ng L-1, respectively, which were significantly lower than those obtained by fluorescence polarization immunoassay using the same immunoreagents. Owing to its operation and highly sensitivity, the proposed assay provides a powerful tool for the detection of AFM1.


Asunto(s)
Aflatoxina M1/análisis , Grafito/química , Inmunoensayo/métodos , Nanopartículas de Magnetita/química , Aflatoxina B1/química , Aflatoxina B1/inmunología , Aflatoxina M1/inmunología , Animales , Anticuerpos Inmovilizados/inmunología , Anticuerpos Monoclonales/inmunología , Cadaverina/química , Colorantes Fluorescentes/química , Contaminación de Alimentos/análisis , Límite de Detección , Leche/química , Reproducibilidad de los Resultados , Rodaminas/química , Espectrometría de Fluorescencia
10.
J Environ Manage ; 299: 113605, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34454203

RESUMEN

Multifunctional cultivated land has both sides of supply and demand, and their matches are very important to boost the high-quality development of agriculture and rural areas. The supply-demand match index and GIS spatial analysis were employed to explore the supply-demand mismatches and synergic strategies of multifunctional cultivated land. Taking the Wuhan Metropolitan Area (WMA), China as an example, we obtained the following results: (1) There were obvious supply-demand mismatches of multifunctional cultivated land in the production function, ecological function, and landscape culture function. The spatial distribution of supply-demand mismatches of the three different functions of cultivated land is different. The supply of cultivated land production function is less than the demand, while the supply of landscape culture function is greater than the demand. The supply matches the demand of cultivated land in the ecological function. (2) The supply-demand mismatches of multifunctional cultivated land have scale effects. From the 1 km × 1 km grid scale to the township, county (district), and prefecture-level city scales, the proportion of deficit regions of production function and ecological function decreases with increasing scale. In contrast, the deficit regions of landscape culture function are always concentrated in the center of the WMA. It is considered that we should improve the supply of cultivated land in the production function, protect ecological function and enhance the demand of landscape culture function. Moreover, the management of multifunctional cultivated land needs to strengthen the multiscale spatial linkage and differential strategies of the supply side and demand side.


Asunto(s)
Agricultura , Conservación de los Recursos Naturales , China , Ciudades , Análisis Espacial
11.
J Environ Manage ; 285: 112054, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33556701

RESUMEN

Cropland protection strategies have provided a strong contribution to limit cropland transformation worldwide. However, it negatively affects ecological land (e.g., forest, grassland, and wetland). Identifying a win-win approach for cropland protection and ecological conservation is important. Land use optimization plays a vital role in solving conflicts among land uses. Thus, in this research, taking China (mainland) as the study area, we optimized the spatial distribution of urban land and cropland to balance the requirement of cropland protection strategies and their negative effects on ecological land according to the spatial heterogeneity of land agricultural production capacity by using the LAND System Cellular Automata model for Potential Effects (LANDSCAPE). Specifically, we developed three optimization scenarios from compensational, occupancy, and occupancy and compensational sectors. We also developed one non-optimization scenario to remain comparable. Results show that compared with the non-optimization scenario, the reduced loss of ecological land in compensational, occupancy, and occupancy and compensational optimization scenario is 7180, 247, and 7277 km2, respectively. Our research indicates that we should prioritize the quality of compensated cropland when developing cropland protection strategies and planning, considering the low efficiency of the occupancy optimization and the cost of policymaking and implementing.


Asunto(s)
Conservación de los Recursos Naturales , Bosques , Agricultura , China , Productos Agrícolas , Ecosistema
12.
J Integr Neurosci ; 19(1): 21-29, 2020 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-32259883

RESUMEN

The neuroprotective role of Fructus Broussonetiae in a model of chronic cerebral hypoperfusion with cognitive decline was focused on neural plasticity and microglia/macrophage polarization. Chronic cerebral hypoperfusion was induced by bilateral common carotid artery ligation. Fructus Broussonetiae shortened escape latency and added the number of platform crossings of rats, up-regulated the expression of synaptophysin in the gray matter and increased myelin basic protein expression in the white matter. Further mechanistic experiments were conducted to examine microglia activation and M1/M2 polarization. It was shown that Fructus Broussonetiae reduced the activation of microglia revealed by decreased expression of ionized calcium-binding adapter molecule-1, inhibited M1 polarization of microglia and improved microglial M2 polarization shown by down-regulated the expression of inducible nitric oxide synthase and Fc fragment of IgG receptor IIIa and up-regulated the expression of arginase-1. In conclusion, the Chinese herb Fructus Broussonetiae can improve cognitive function following chronic cerebral hypoperfusion by down-regulating the activation of microglia, inhibiting microglial M1 polarization, and improving neural plasticity.


Asunto(s)
Encéfalo/efectos de los fármacos , Broussonetia , Trastornos Cerebrovasculares/complicaciones , Disfunción Cognitiva/fisiopatología , Aprendizaje por Laberinto/efectos de los fármacos , Microglía/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Memoria Espacial/efectos de los fármacos , Animales , Encéfalo/fisiopatología , Trastornos Cerebrovasculares/fisiopatología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/prevención & control , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Microglía/fisiología , Ratas Sprague-Dawley
13.
Int J Mol Sci ; 21(7)2020 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-32230936

RESUMEN

Ovarian cancer is the most deadly gynecologic cancer among women worldwide. Poor response to current treatment makes it necessary to discover new diagnostic biomarkers to detect the cancer early and develop new and effective prevention strategies. Calcitriol, the active metabolite of vitamin D, protects against multiple cancers through unelucidated mechanisms. The oncogenic long non-coding RNA (lncRNA) CCAT2 (colon cancer associated transcript 2) is overexpressed in ovarian cancer. Here, we foundd that calcitriol inhibited CCAT2 expression in ovarian cancer cell lines. Treatment with calcitriol inhibited ovarian cancer cell proliferation, migration, and invasion. As a result of CCAT2 inhibition, calcitriol decreased the binding of transcription factor TCF7L2 (TCF4) to the MYC promoter, resulting in the repression of c-Myc protein expression. Our results suggest a novel anti-cancer mechanism of vitamin D by targeting CCAT2 in ovarian cancer. The findings may help develop vitamin D as a practical and inexpensive nutraceutical for ovarian cancer prevention.


Asunto(s)
Carcinoma Epitelial de Ovario/prevención & control , Neoplasias Ováricas/prevención & control , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Vitamina D/farmacología , Calcitriol/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genes myc , Humanos , Oncogenes , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteína 2 Similar al Factor de Transcripción 7/metabolismo , Factores de Transcripción , Cicatrización de Heridas
14.
J Environ Manage ; 265: 110515, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32275243

RESUMEN

When cropland expansion encroaches on ecological land (e.g., forest, grassland, wetland), it seriously affects carbon storage which plays an important role in global climate change. Taking Hubei as the study area, this study explored the effects of cropland expansion on carbon storage in both 2000-2010 and 2010-2030 in different scenarios by using the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model and the LAND System Cellular Automata model for Potential Effects (LANDSCAPE). The results showed that cropland expansion led to a massive loss of carbon storage (1.76 Tg C) during 2000-2010, which is expected to continue during 2010-2030 in different scenarios. The loss is predicted to be 3.70 Tg C in the Business-As-Usual scenario and be 0.88 Tg C in the Requisition-Compensation Balance of Cropland Policy scenario. Noticeably, the loss of carbon storage due to cropland expansion was 1.12 times more than that due to urban expansion during 2000-2010. For the period of 2010-2030, the loss of carbon storage caused by cropland expansion is predicted to be 3.89 times more than that caused by urban expansion in the Business-As-Usual scenario, while the losses caused by cropland expansion and urban expansion are predicted to be almost equal in the Requisition-Compensation Balance of Cropland Policy scenario. The main cause of carbon storage loss due to cropland expansion is that it leads to the considerable loss of forest and wetland. This study highlights the importance of considering the loss of carbon storage caused by cropland expansion when conducting cropland protection policies and land use planning.


Asunto(s)
Carbono , Ecosistema , Secuestro de Carbono , China , Conservación de los Recursos Naturales , Productos Agrícolas
15.
Molecules ; 25(18)2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899627

RESUMEN

Cyclooxygenase-2 (COX-2) imaging agents are potent tools for early cancer diagnosis. Almost all of the COX2 imaging agents using celecoxib as backbone were chemically modified in the position of N-atom in the sulfonamide group. Herein, a novel COX-2 probe (CCY-5) with high targeting ability and a near-infrared wavelength (achieved by attaching a CY-5 dye on the pyrazole ring of celecoxib using a migration strategy) was evaluated for its ability to probe COX-2 in human cancer cells. CCY-5 is expected to have high binding affinity for COX-2 based on molecular docking and enzyme inhibition assay. Meanwhile, CCY-5 caused stronger fluorescence imaging of COX-2 overexpressing cancer cells (Hela and SCC-9 cells) than that of normal cell lines (RAW 264.7 cells). Lipopolysaccharide (LPS) treated RAW264.7 cells revealed an enhanced fluorescence as LPS was known to induce COX-2 in these cells. In inhibitory studies, a markedly reduced fluorescence intensity was observed in cancer cells, when they were co-treated with a COX-2 inhibitor celecoxib. Therefore, CCY-5 may be a selective bioimaging agent for cancer cells overexpressing COX-2 and could be useful as a good monitoring candidate for effective diagnosis and therapy in cancer treatment.


Asunto(s)
Celecoxib/farmacología , Ciclooxigenasa 2/metabolismo , Colorantes Fluorescentes/síntesis química , Rayos Infrarrojos , Neoplasias/diagnóstico , Animales , Celecoxib/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/farmacología , Fluorescencia , Humanos , Lipopolisacáridos/farmacología , Ratones , Simulación del Acoplamiento Molecular , Neoplasias/patología , Células RAW 264.7
16.
Int J Mol Sci ; 20(22)2019 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-31744051

RESUMEN

Colorectal cancer (CRC) is the third most common cancer and has a high metastasis and reoccurrence rate. Long noncoding RNAs (lncRNAs) play an important role in CRC growth and metastasis. Recent studies revealed that lncRNAs participate in CRC progression by coordinating with microRNAs (miRNAs) and protein-coding mRNAs. LncRNAs function as competitive endogenous RNAs (ceRNAs) by competitively occupying the shared binding sequences of miRNAs, thus sequestering the miRNAs and changing the expression of their downstream target genes. Such ceRNA networks formed by lncRNA/miRNA/mRNA interactions have been found in a broad spectrum of biological processes in CRC, including liver metastasis, epithelial to mesenchymal transition (EMT), inflammation formation, and chemo-/radioresistance. In this review, we summarize typical paradigms of lncRNA-associated ceRNA networks, which are involved in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the competitive crosstalk among RNA transcripts and the novel targets for CRC prognosis and therapy.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/diagnóstico , ARN Largo no Codificante/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Resistencia a Antineoplásicos/genética , Transición Epitelial-Mesenquimal/genética , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Mensajero/metabolismo
17.
Bioorg Med Chem Lett ; 26(16): 4146-53, 2016 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-27426298

RESUMEN

A series of quinoxaline 1,4-di-N-oxide derivatives variously substituted at C-2 position were synthesized and evaluated for in vitro antimycobacterial activity. Seventeen compounds exhibited potential activity (MIC ⩽6.25µg/mL) against Mycobacterium tuberculosis (H37Rv), in particular the compounds 3d and 3j having an MIC value of 0.39µg/mL. None of the compounds exhibited cytotoxicity when using an MTT assay in VERO cells. To further investigate the structure-activity relationship, CoMFA (q(2)=0.507, r(2)=0.923) and CoMSIA (q(2)=0.665, r(2)=0.977) models were performed on the basis of antimycobacterial activity data. The 3D-QSAR study of these compounds can provide useful information for further rational design of novel quinoxaline 1,4-di-N-oxides for treatment of tuberculosis.


Asunto(s)
Antituberculosos/síntesis química , Relación Estructura-Actividad Cuantitativa , Quinoxalinas/química , Animales , Antituberculosos/química , Antituberculosos/farmacología , Chlorocebus aethiops , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Óxidos/química , Quinoxalinas/síntesis química , Quinoxalinas/farmacología , Células Vero
18.
Abdom Radiol (NY) ; 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38446180

RESUMEN

OBJECTIVES: To develop and validate a radiomics-based model for predicting SOX9-positive hepatocellular carcinoma (HCC) using preoperative contrast-enhanced computed tomography (CT) images. METHODS: From January 2013 to April 2017, patients with histologically proven HCC who received systemic sorafenib treatment after curative resection were retrospectively enrolled. Radiomic features were extracted from portal venous phase CT images and selected to build a radiomics score using logistic regression analysis. The factors associated with SOX9 expression were selected and combined by univariate and multivariate analyses to establish clinico-liver imaging (CL) model and clinico-liver imaging-radiomics (CLR) model. Diagnostic performance was measured by area under curve (AUC). Overall survival (OS) and recurrence-free survival (RFS) rates were compared using Kaplan-Meier method. RESULTS: A total of 108 patients (training cohort: n = 80; validation cohort: n = 28) were enrolled. Multivariate analyses revealed that the albumin-bilirubin grade and tumor size were significant independent factors for predicting SOX9-positive HCCs and were included in the CL model. The CLR model integrating the radiomics score with albumin-bilirubin grade and tumor size showed better discriminative performance than the CL model with AUCs of 0.912 and 0.790 in the training and validation cohorts. Survival curves for RFS and OS showed that SOX9 expression was closely related to the prognosis of HCC patients. RFS and OS rates were significantly lower in patients with SOX9-positive than SOX9-negative (51.02% vs. 75.00% at 1-year RFS rates; 76.92% vs. 94.94% at 2-year OS rates). CONCLUSION: Radiomics signatures may serve as noninvasive predictors for SOX9 status evaluation in patients with HCC and may aid in constructing individualized treatment strategies.

19.
Water Res ; 253: 121299, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38387265

RESUMEN

As the key stage for purifying wastewater, elimination of emerging contaminants (ECs) is found to be fairly low in wastewater treatment plants (WWTPs). However, less knowledge is obtained regarding the transformation pathways between various chemical structures of ECs under different treatment processes. This study unveiled the transformation pathways of ECs with different structures in 15 WWTPs distributed across China by simplified network analysis (SNA) we proposed. After treatment, the molecular weight of the whole component of wastewater decreased and the hydrophilicity increased. There are significant differences in the structure of eliminated, consistent and formed pollutants. Amino acids, peptides, and analogues (AAPAs) were detected most frequently and most removable. Benzenoids were refractory. Triazoles were often produced. The high-frequency reactions in different WWTPs were similar, (de)methylation and dehydration occurred most frequently. Different biological treatment processes performed similarly, while some advanced treatment processes differed, such as a significant increase of -13.976 (2HO reaction) paired mass distances (PMDs) in the chlorine alone process. Further, the common structural transformation was uncovered. 4 anti-hypertensive drugs, including irbesartan, valsartan, olmesartan, and losartan, were identified, along with 22 transformation products (TPs) of them. OH2 and H2O PMDs occurred most frequently and in 80.81 % of the parent-transformation product pairs, the intensity of the product was higher than parent in effluents, whose risk should be considered in future assessment activity. Together our results provide a macrography perspective on the transformation processes of ECs in WWTPs. In the future, selectively adopting wastewater treatment technology according to structures is conductive for eliminating recalcitrant ECs in WWTPs.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Aguas Residuales , Contaminantes Químicos del Agua/química , Irbesartán/análisis , Losartán/análisis
20.
Zhonghua Xin Xue Guan Bing Za Zhi ; 41(6): 514-8, 2013 Jun.
Artículo en Zh | MEDLINE | ID: mdl-24113046

RESUMEN

OBJECTIVE: To observe the association between baseline pulse pressure (PP) level and new-onset cardio-cerebrovascular events in diabetic population. METHODS: Physical examination data between July 2006 to October 2007 from a total of 101 510 employees of Kailuan Group were reviewed, 8306 subjects with a fasting plasma glucose level of ≥ 7.0 mmol/L or with confirmed diabetes diagnosis and were enrolled in this prospective cohort study. Subjects were followed up for 38-53 (48.1 ± 3.1) months and the cardio-cerebrovascular events were obtained every six months, association between baseline PP and new-onset cardio-cerebrovascular events in the diabetic population were analyzed. RESULTS: (1) Incidences of total cardio-cerebrovascular events in the PP groups were 3.4%, 2.8%, 4.5%, 6.4%, respectively. Incidences of cerebral infarction events and myocardial infarction were 2.1%, 1.6%, 2.9%, 3.9% and 1.1%, 0.7%, 1.0%, 1.7%, respectively. (2) Multivariate Cox's proportional hazards regression analysis indicated that baseline PP group was the risk factor for total cardio-cerebrovascular events, cerebral infarction events and myocardial infarction, and the risk for all the events of the PP ≥ 60 mm Hg (1 mm Hg = 0.133 kPa) group was increasing. The values of RR(95%CI) were 1.88 (95%CI 1.34-2.65, P < 0.01), 1.92 (95%CI 1.23-2.99, P < 0.01) and 1.52 (95%CI 0.82-2.81, P > 0.05) after adjust the other factors.(3) In line with increasing level of baseline PP, age, BMI, SBP, DBP, HDL-C, and hs-CRP levels significantly increased in this diabetic population (P < 0.01 or P < 0.05). CONCLUSION: The level of high baseline PP is a risk factor for new-onset cardio-cerebrovascular events in diabetic population.


Asunto(s)
Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
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