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A highly sensitive dual-recognition fluorescence amplification method is presented for lipopolysaccharide (LPS) detection based on boronic functionalized aptamer macroarrays with dual-recognition and isothermal amplification. The surface of the polystyrene microplate was firstly carboxylated, and then, 3-aminophenylboronic acid was conjugated to the carboxyl groups through EDC/NHS reaction, creating boronic acid groups as the capture moiety for LPS. A recognition DNA aptamer labeled with the fluorescent dye 6-FAM, which exhibits specificity towards LPS, was selected as the signal reporting moiety. By introducing primers and Klenow enzyme, the fluorescent-labeled aptamers are released from the microplate bottom, and double-stranded structures were formed via isothermal amplification. The addition of SYBR Green I, which strongly fluoresces upon binding to the double-stranded structures, enables signal amplification and detection. This detection method exhibits a linear range of 1-10,000 ng/mL and has a detection limit as low as 401.93 pg/mL. This analytical approach shows high selectivity and sensitivity and may serve as a universal platform in lipopolysaccharide detection.
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Aptámeros de Nucleótidos , Ácidos Borónicos , Colorantes Fluorescentes , Límite de Detección , Lipopolisacáridos , Técnicas de Amplificación de Ácido Nucleico , Aptámeros de Nucleótidos/química , Lipopolisacáridos/análisis , Técnicas de Amplificación de Ácido Nucleico/métodos , Ácidos Borónicos/química , Colorantes Fluorescentes/química , Técnicas Biosensibles/métodosRESUMEN
Precise three-dimensional (3D) bioprinting designs enable the fabrication of unique structures for 3D-cell culture models. There is still an absence of real-time detection tools to effectively track in situ 3D-cell performance, hindering a comprehensive understanding of disease progression and drug efficacy assessment. While numerous bioinks have been developed, few are equipped with internal sensors capable of accurate detection. This study addresses these challenges by constructing a 3D-bioprinted hepar-on-a-chip embedded with graphene quantum dot-capped gold nanoparticle-based plasmonic sensors, featuring strong surface-enhanced Raman scattering (SERS) enhancement, biostability, and signal consistency. Such an integrated hepar-on-a-chip demonstrates excellent capability in the secretion of liver function-related proteins and the expression of drug metabolism and transport-related genes. Furthermore, the on-site detection of cell-secreted biomarker glutathione transferase α (GST-α) was successfully achieved using the plasmonic probe, with a dynamic linear detection range of 20-500 ng/mL, showcasing high anti-interference and specificity for GST-α. Ultimately, this integrated hepar-on-a-chip system offers a high-quality platform for monitoring liver injury.
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Oro , Grafito , Puntos Cuánticos , Grafito/química , Humanos , Oro/química , Puntos Cuánticos/química , Nanopartículas del Metal/química , Bioimpresión/métodos , Dispositivos Laboratorio en un Chip , Impresión Tridimensional , Espectrometría Raman/métodos , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentaciónRESUMEN
OBJECTIVE: Hospital management and medical treatment changed during the coronavirus disease 2019 (COVID-19) pandemic. This study investigated the impact of the COVID-19 pandemic on patients with bladder cancer. METHODS: In this multicenter retrospective study, we collected information from the electronic medical records of outpatients who underwent cystoscopy and inpatients with confirmed bladder cancer in three hospitals in Nanjing (two province-level and one county-level hospitals) in 2019 and 2020. Patients' home addresses, treatment methods, length of stay, and pathology were compared between the periods. RESULTS: In total, 4048 outpatients and 1242 inpatients were included. The average number of cystoscopies decreased significantly during the lockdown. In province-level hospitals, the number of cystoscopies increased gradually as the pandemic was brought under control but remained lower than that in 2019, whereas the number grew in 2020 in county-level hospitals. The rates of recurrence and radical cystectomy were higher in 2020 than in 2019. No significant difference in the pathological grade was observed. More patients who underwent radical cystectomy were diagnosed with muscle-invasive bladder cancer during the 2020 lockdown. CONCLUSION: The pandemic severely affected patients with bladder cancer, mainly in their choice of institution and treatment.
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COVID-19 , Neoplasias de la Vejiga Urinaria , Humanos , Pandemias , Estudios Retrospectivos , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/cirugía , Cistectomía/métodosRESUMEN
The irrational use of natural compounds in the treatment of diseases can lead to serious side effects, especially hepatoxicity, and its toxic effects are usually cumulative and imperceptible. Therefore, an accurate sensing platform is urgently needed to monitor the hepatotoxicity of natural compounds. Here, we deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and a thorough validation was adopted to evaluate the bioprinted hepatic constructs. The engineered hepar-platform was then employed to access its biological response toward Emodin (EM) and Triptolide (TP), two typical hepatotoxic natural compounds. Subsequently, we integrated it with a robust fluorescent sensor based on hybridization chain reaction amplification strategy (HCR) to monitor the early hepatotoxic biomarker - glutathione-S-transferase-alpha (GST-α) secreted by this 3D constructs. Our study was the first attempt to construct an accurate hepar-on-a-sensor platform that could effectively detect GST-α for monitoring the hepatoxic effects of natural compounds. The limit of detection of the platform was 0.3 ng ml-1 and the accuracy of this platform was verified by enzyme linked immunosorbent assay. Furthermore, the variation of GST-α induced by EM and TP was consistent with hepatotoxicity studies, thus providing an important application value for evaluating the hepatotoxicity of natural compounds. STATEMENT OF SIGNIFICANCE: 1. We deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and elucidated the essential reasons why hybrid bioinks more suitable for 3D extrusion from biomaterials itself. Also, a thorough validation associated with a series of important proteins and genes involved in liver cell metabolism was adopted to evaluate the bioprinted hepatic constructs accurately 2. Glutathione-S-transferase-alpha is a soluble trace biomarker for acute hepatotoxic injury, the hepatotoxic effects of natural compounds on the secretion of GST-α has not been reported to date. We integrated our 3D hepar-platform with recognition molecules-aptamers and HCR amplification strategy to monitor the variation of GST-α, aiming at developing a robust and stable fluorescent biosensing platform to monitor the hepatoxicity of natural compounds.
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Bioimpresión , Enfermedad Hepática Inducida por Sustancias y Drogas , Humanos , Poloxámero , Hidrogeles , Biomarcadores , Colorantes , Alginatos , Glutatión , Oligopéptidos , Impresión Tridimensional , Andamios del Tejido , Ingeniería de TejidosRESUMEN
Norcantharidin (NCTD), a demethylated derivative of cantharidin, is an anticancer active component in traditional Chinese medicine. At present, the main methods for finding its target proteins are pharmacological methods and biophysical screening, which cannot achieve the purpose of efficient and accurate screening. Here we established a new analytical method for specific fishing and assisted imaging for norcantharidin target proteins. For the AIE supramolecule probe, the benzophenone azide (BPA) fluorescent nanoparticles with strong AIE properties were encapsulated in biocompatible DSPE-PEG that covalently coupled with NCTD (named BPA@NCTD NPs). The target proteins of NCTD can be captured by BPA@NCTD NPs, and then be detected to investigate the potential signaling pathways. The screened differential proteins were analysed through the protein and signaling pathway database, and multiple signaling pathways were obtained and verified. The mechanism of norcantharidin in inhibiting the migration and invasion of A549 cells through the P53 signaling pathway was confirmed by Western blot experiments. Our research showed that AIE supramolecule probe BPA@NCTD NPs has the dual functions of specific screening of A549 cells target proteins and biological imaging, which not only offers a good anti-fluorescence quenching ability for the dynamic imaging process of NCTD, but also provides a novel and efficient specific method for efficient analysis of target proteins and signal pathways.
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Compuestos Bicíclicos Heterocíclicos con Puentes , Transducción de Señal , Línea Celular Tumoral , Apoptosis , Proliferación CelularRESUMEN
To increase the solubility and targeting efficiency of curcumin (CCM) to tumors, transferrin (Tf)-CCM nanoparticles (NPs-CCM) with a CCM loading capacity of 5.2% were fabricated by Tf denaturation with hydrochloric acid, a denaturing agent, to open the hydrophobic cavity of Tf. The NPs-CCM were approximately 160 nm in size with a spherical shape. The solubility of the CCM in the nanoparticles was approximately 100,000 times greater than that of CCM alone (11 ng mL-1 vs 1.11 mg mL-1, respectively). The changes in the fluorescence spectra of Tf and 1-(anilinon)-aphthalene-8-sulfonic acid (ANS) in the NP-CCM preparation indicated that the polarity of certain hydrophobic and hydrophilic groups of Tf changed. CCM treatment of A549 cells resulted in a decrease in the mitochondrial membrane potential (MMP) and induced apoptosis through mitochondrial dependence. CCM increased the expression of phosphorylated c-Jun N-terminal kinase (JNK), P38, and extracellular signal-regulated kinase (ERK) but had a weak effect on the expression of nonphosphorylated JNK, P38, and ERK, which showed that the mitogen-activated protein kinase signaling (MAPK) transduction pathway is involved in CCM-mediated apoptosis. The half maximal inhibitory concentration (IC50) of NPs-CCM was higher than that of free CCM in A549 (16.41 ± 0.86 vs 12.51 ± 3.9 (µg mL-1), p = 0.036) and MCF-7 (9.31 ± 0.11 vs 2.44 ± 3.76 (µg mL-1), p < 0.0037) tumor cells, however the former had a greater tumor-targeting in vivo. Without the side effects of polyoxyethylene castor oil/ethanol as solvent, the hemolysis effect of NPs-CCM (0.05-1 mg mL-1) was notably lower than that of free CCM (p < 0.05). It was estimated that the half maximal lethal dose (LD50) of NPs-CCM was approximately two times that of CCM (100 mg kg-1 vs 50 mg kg-1), and the former had many advantages over that of free CCM in terms of lower toxicity and better targeting; thus, NPs-CCM can be administered at higher doses to acquire better antitumor effects than CCM alone, indicating that NPs-CCM are an effective and safe carrier for CCM delivery.
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Curcumina , Nanopartículas , Curcumina/química , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Solubilidad , Transferrina/químicaRESUMEN
Diabetes can cause various complications and affect the normal functioning of the human body. A theranostic and diagnostic platform for real-time glycemia sensing and simultaneous self-regulated release of insulin is desired to improve diabetic patients' life quality. Here, we describe a theranostic microneedle array patch, which enables the achievement of visualization quantification of glycemia and simultaneously self-regulated release of insulin. The microneedle patch (MNDF) was fabricated by crosslinking of 3-aminophenylboronic acid (ABA)-modified sodium alginate and chondroitin sulfate. The hierarchical structure consisted of a tip part containing mineralized insulin particles and glucose oxidase (GOD) for insulin release, and a base surface embodying 3,3',5,5'-tetramethylbenzidine (TMB) and (horseradish peroxidase) HRP for real-time glycemia sensing. In the presence of glucose, GOD converts glucose into H+ and H2O2, driving gradual dissolution of the calcium layer of insulin particles, resulting in long-acting release of insulin. By the bio-catalytic action of HRP, the generated H2O2 brings about a visible color change allowing the glucose level at the base surface to be read out. We believe that the theranostic microneedle array patch can act as a promising alternative for future clinical applications.
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Diabetes Mellitus Experimental , Insulina , Animales , Glucemia , Diabetes Mellitus Experimental/tratamiento farmacológico , Humanos , Peróxido de Hidrógeno/química , Insulina/química , Medicina de PrecisiónRESUMEN
Recently, some metabolites in skin interstitial fluid (SIF) have become emerging re×sources for early disease diagnosis. However, their low level in SIF and difficulty to sampling are the biggest obstacle to further potential application. Here, a swellable microneedle array patch (MNAP) with high mechanical strength is presented, and the rapid enrichment of positively charged metabolites is achieved. The MNAP is fabricated by poly (chondroitin sulfate-acrylamido-2-methylpropane sulfonic acid)-gold nanoparticles (GNPs) composites via a micro-molding. The negatively charged copolymer hydrogel not only enrich positively charged metabolites, but also provide swellable capacity. The in situ synthesis of GNPs in the process of copolymerization make the GNPs cross-link to the hydrogel, which further enhance the MNAP mechanical strength and enrichment efficiency for positively charged metabolites. By using the MNAP, around 5 mg SIF in 10 min from the high fat/cholecalciferol/methimazole-induced atherogenesis rat is extracted and 23 metabolites including 13 quaternary ammonium cationic compounds can be detected and quantified by using a LC-QTOF-MS. Dysregulated L-carnitine and choline metabolism are discovered a week earlier in the SIF than in the serum, achieving early diagnosis of the metabolism syndrome disease. This MNAP also helps users complete home sampling for early disease diagnosis and monitoring.
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Nanopartículas del Metal , Agujas , Animales , Diagnóstico Precoz , Oro , Ratas , PielRESUMEN
Melanogenesis is the process for the production of melanin, which is the primary cause of human skin pigmentation. Skin-whitening agents are commercially available for those who wish to have a lighter skin complexions. To date, although numerous natural compounds have been proposed to alleviate hyperpigmentation, insufficient attention has been focused on potential natural skin-whitening agents and their mechanism of action from the perspective of compound classification. In the present article, the synthetic process of melanogenesis and associated core signaling pathways are summarized. An overview of the list of natural skin-lightening agents, along with their compound classifications, is also presented, where their efficacy based on their respective mechanisms of action on melanogenesis is discussed.
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An integrated aptamer macroarray functionalized with reduced graphene oxide (rGO) to specifically capture and sensitively detect cancer cells is reported. The capture for cancer cells is based on effective recognition of the modified rGO surface through the aptamer against epithelial cell adhesion molecule (EpCAM). The rough structure of rGO enhances morphologic interactions between rGO film interface and the cancer cells, while super-hydrophilicity of modified rGO hinders nonspecific cell capture. The synergistic interactions offer the aptamer macroarray high efficiency of cancer cell capture. By means of a turn-on fluorescence strategy based on the conformation change of the aptamer induced by the target recognition, the enriched cancer cells can be directly read out at excitation/emission wavelengths of 550/680 nm without washing, separation, and dying steps. The working range is 1 × 102 to 2 × 104 cells per mL with a detection limit of 22 cells per mL. The results indicate that the aptamer macroarray has a considerable foreground for early diagnosis, therapy, and monitoring of cancer. Graphical abstract.
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Aptámeros de Nucleótidos/química , Separación Celular/métodos , Grafito/química , Células Neoplásicas Circulantes , Secuencia de Bases , Línea Celular Tumoral , Molécula de Adhesión Celular Epitelial/química , Fluorescencia , Transferencia Resonante de Energía de Fluorescencia , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ácidos Nucleicos Inmovilizados/química , Límite de Detección , Pirenos/químicaRESUMEN
The kidney renal clear cell carcinoma (KIRC) with poor prognosis is the main histological subtype of the renal cell carcinoma, accounting for 80-90% of patients. Currently, the N6-methyladenosine (m6A) epitranscriptional modification draws much attention. The m6A RNA modification, the most plentiful internal modification of mRNAs and noncoding RNAs in the majority of eukaryotes, regulates mRNAs at different levels and is involved in disease occurrence and progression. The GTExPortal and TCGAportal were applied to investigate the METTL14 mRNA expression in different tissues and KIRC stages. The Human Protein Atlas was used to verify the location of METTL14 in KIRC tissues. The main microRNAs (miRNAs) related to KIRC were analyzed using OncoLnc and starBase, while corresponding circular RNAs (circRNAs) interacting with miRNAs were predicted via circBank; then, the METTL14-miRNA-circRNA interaction network was established. The level of methyltransferase-like 14 (METTL14) mRNA was significantly lower in KIRC tissues compared with normal kidney tissues, which was relative to clinical and pathological stages. circRNAs may regulate METTL14 mRNA as miRNAs sponge to affect the KIRC progression. METTL14 mRNA is likely to regulate PTEN mRNA expression via changing its m6A RNA modification level. METTL14 mRNA expression negatively correlated with the KIRC stages and positively correlated with KIRC patients' overall survival, which has great potential to serve as a clinical biomarker in KIRC.
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Carcinoma de Células Renales/genética , Biología Computacional/métodos , Regulación hacia Abajo , Neoplasias Renales/genética , Metiltransferasas/genética , Anciano , Biomarcadores de Tumor/genética , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , MicroARNs/genética , Persona de Mediana Edad , Pronóstico , ARN Circular/genética , Análisis de SupervivenciaRESUMEN
BACKGROUND The present systematic review and meta-analysis was performed to explore the possible effect of bariatric surgery on semen parameters. MATERIAL AND METHODS Studies on the effect of bariatric surgeries on semen parameters were collected by searching Cochrane Library, PUBMED, EMBASE, MEDLINE, and CNKI databases. We extracted information on essential data and outcome measures, including study design, bariatric surgery, and semen parameters at baseline and after the surgery from the included studies, and STATA 12.0 software was applied to conduct the meta-analysis. Predefined subgroup analyses were also conducted by study design and bariatric surgical procedures. The standard mean difference (SMD) was calculated to estimate the effect on semen parameters. RESULTS After the literature search, 6 articles that fulfilled the inclusion criteria were included in the present meta-analysis. The results revealed that patients who had undergone gastric bypass surgery had an increase in semen volume (SMD (95%CI)=0.583 (0.121-1.045), p=0.013). However, the seminal concentration (overall, SMD (95%CI)=-0.123 (-0.418-0.173), p=0.416) and the semen progressive motility (overall SMD (95%CI)=0.148 (-0.148-0.444), p=0.328) remained unchanged after the bariatric surgery. Nevertheless, semen normal morphology experienced an increase in the subgroup of prospective design and sleeve gastrectomy (prospective study, SMD (95%CI)= 0.385 (0.074-0.697), p=0.015, sleeve gastrectomy, SMD (95%CI)=0.880 (0.465-1.296), p=0.000; overall, SMD (95%CI)=0.372 (0.068-0.677), p=0.017). CONCLUSIONS In conclusion, based on the limitations of the present meta-analysis, definite conclusions cannot be reached regarding the possible effect of bariatric surgery on semen parameters.
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Cirugía Bariátrica/efectos adversos , Semen/fisiología , Derivación Gástrica/efectos adversos , Humanos , Masculino , Análisis de Semen/métodosRESUMEN
Accumulative evidences have underpinned the nature candidates from Chinese medicine (CM), particularly CM served as blood activating and stasis resolving (BASR, Huoxue Huayu in Chinese) by targeting tumor-associated angiogenesis. However, recent experiment research on the therapeutic angiogenesis by BASR-CM attracts wide attention and discussion. This opinion review focused on the underlying link between two indications and anticipated that (1) BASR-CM might emphasize on a balanced multi-cytokines network interaction; (2) BASR-CM might address on the nature of diseases prior to differently affecting physiological and pathological angiogenesis; (3) BASR-CM might mainly act on perivascular cells, either promotes arteriogenesis by increasing arteriogenic factors in ischemic diseases, or simultaneously keep a quiescent vasculature to impede angiogenesis in tumor context.
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Medicamentos Herbarios Chinos/uso terapéutico , Neovascularización Patológica/sangre , Neovascularización Patológica/tratamiento farmacológico , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Medicamentos Herbarios Chinos/química , Humanos , Modelos BiológicosRESUMEN
Activated platelets have been recognized as an accessory character in the cascade of tumor hematogenous metastasis, and intervention of tumor cell attachment to the activated platelets or microemboli formation might be a leading strategy to prevent tumor cells surviving in the blood vessels and sequential metastasis. Recently, we have demonstrated that holothurian glycosaminoglycan (hGAG), a sulfated polysaccharide with potent anticoagulant activity extracted from the sea cucumber Holothuria leucospilota Brandt, was highly efficacious against tumor metastasis. In this study, we identified the potential effects of hGAG on the disruption of interactions of cancer cells and platelets and the underlying mechanisms, which were supported by the following evidence: hGAG (1) inhibited thrombin-induced platelet activation and aggregation, (2) reduced adhesion between platelet and breast cancer cells, and abrogated platelets/cancer cells adhering to fibrinogen, (3) attenuated platelet-cancer cell complex formation (the number and size of aggregates) and (4) suppressed both mRNA and protein levels of ß1 and ß3 integrins, matrix metalloproteinase (MMP)-2 and MMP-9, while increasing the expression of the MMP inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 in MDA-MB-231 cells. These results suggested that both the antiplatelet properties and mitigation of the levels of cellular adhesion molecules contributed to the anticancer effects of hGAG, and might thus be exploited for clinical adjuvant therapy to attenuate tumor hematogenous metastasis.
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Antineoplásicos/farmacología , Plaquetas/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Adhesión Celular/efectos de los fármacos , Glicosaminoglicanos/farmacología , Holothuria/química , Integrinas/metabolismo , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Animales , Antineoplásicos/aislamiento & purificación , Plaquetas/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Femenino , Fibrinógeno/metabolismo , Regulación Neoplásica de la Expresión Génica , Glicosaminoglicanos/aislamiento & purificación , Humanos , Integrina beta1/genética , Integrina beta1/metabolismo , Integrina beta3/genética , Integrina beta3/metabolismo , Integrinas/genética , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Metástasis de la Neoplasia , Adhesividad Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , ARN Mensajero/metabolismo , Trombina/metabolismo , Factores de Tiempo , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
Cancer related inflammation (CRI) is now recognized as the seventh hallmark in the pathogenesis of many types of malignancies. Paeonol, a natural phenolic component isolated from the root bark of Paeonia moutan, has significant anti-inflammatory activity. Recently, accumulating body of research has revealed potent anti-tumor effects mediated by paeonol. However, little is known about its anticancer mechanism on the basis of CRI. In this study, we observed that paeonol exerted direct anticancer activity through inhibition of cell proliferation, induction of apoptosis, and evident anti-inflammatory effects by reducing proinflammatory cytokines secretion (TNF-α, IL-1ß, IL-6, and TGF-ß) in the conditioned medium of B16F10 mouse melanoma cells. Interestingly, we found that paeonol significantly reversed motility phenotypes in TNF-α- or IL-6-induced B16F10 singe cell and collective migration and invasion in vitro, which were related to affecting epithelial-to-mesenchymal transition (EMT) makers and MMPs expression. In particular, paeonol disrupted both TNF-α-activated NF-κB and IL-6-activated STAT3 signaling pathways in B16F10 cells. EMSA and luciferase assays showed that paeonol abrogated NF-κB binding and NF-κB-driven promoter activity in the presence of TNF-α. Finally, we showed that paeonol attenuated B16F10 spontaneous lung metastases in C57/BL6J mice with down-regulated levels of serum proinflammatory cytokines. Therefore, paeonol possessed antitumor activity in melanoma cells and mice model by interruption of the aggressive feedback through proinflammatory cytokines mediated NF-κB and STAT3 signaling activation. These findings provide a novel treatment strategy that paeonol might be a promising versatile adjuvant therapy for cancer related inflammation.
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Acetofenonas/farmacología , Antineoplásicos Fitogénicos/farmacología , Citocinas/metabolismo , Neoplasias Pulmonares/prevención & control , Melanoma Experimental/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Acetofenonas/uso terapéutico , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Melanoma Experimental/metabolismo , Melanoma Experimental/secundario , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Invasividad Neoplásica , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Recently, many studies explored the role of inflammation parameters such as neutrophil-to-lymphocyte ratio (NLR) in the prognosis of urinary cancers, but the results were not consistent. METHODS: We carried out a meta-analysis of published studies to assess the prognostic value of NLR in patients with urinary cancers. Hazard ratio (OR) with 95% confidence interval (CI) was used to assess the association of NLR and OS and RFS/CSS. RESULTS: The pooled results showed that high NLR was a poor predictor for OS with HR of 1.81 (95%CI: 1.48-2.21; Pheterogeneityâ=â0.005) and RFS/CSS (HRâ=â2.07, 95% CI: 1.65-2.6; Pheterogeneityâ=â0.849). Subgroup analyses revealed that high NLR yielded a worse OS in RCC (HRâ=â1.9, 95%CI: 1.47-2.45; Pheterogeneityâ=â0.003) and a poor RFS/CSS in RCC (HRâ=â1.83, 95%CI: 1.35-2.48; Pheterogeneityâ=â0.709), bladder cancer (HRâ=â2.2, 95%CI: 1.27-3.8; Pheterogeneityâ=â0.447) and urothelial carcinoma (HRâ=â2.58, 95%CI: 1.66-4.01; Pheterogeneityâ=â0.784). CONCLUSION: Our results showed that NLR could act as a significant biomarker in the prognosis of urinary cancers.
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Linfocitos/patología , Neutrófilos/patología , Neoplasias Urológicas/diagnóstico , Pueblo Asiatico , Biomarcadores/análisis , Femenino , Humanos , Inflamación/diagnóstico , Inflamación/etnología , Inflamación/mortalidad , Inflamación/patología , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Neoplasias Urológicas/etnología , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patología , Población BlancaRESUMEN
Pimpinella brachycarpa (Kom.) Nakai (PB) is one of the most favored edible greens grown in Asian regions. In our previously study, we found PB extract had antioxidant effects in vitro. In the present study, an EtOAc soluble extract (PBet) was isolated from PB. Then the antioxidant properties at cellular level, phytochemical composition and toxicity of PBet were examined. The results indicated that PBet (0.5-2mg/mL) could protect Bel-7404 cells from H(2)O(2) induced cell damage through scavenging of intracellular ROS. Moreover, myristic acid, 24ζ-methyl-5α-lanosta-25-one, ß-sitosterol, pregnenolone and ß-daucosterol were firstly isolated from PB. In addition, PBet (0.75g/kg BW, ig) had no acute toxicity and it (0.03-0.12g/kg BW, ig, 7 d) could not influence the rate of bone marrow polychromatic erythrocytes micronucleus and chromosome aberration in KM mice. All above findings suggested that PBet could be considered as a safe functional food with antioxidant activities.
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Antioxidantes/toxicidad , Pimpinella , Extractos Vegetales/toxicidad , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Ratones , Pruebas de Mutagenicidad , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo , Sitoesteroles/análisis , Pruebas de Toxicidad AgudaRESUMEN
Salidroside, a major component of Rhodiola rosea L., has shown various pharmacological functions, including antioxidant effects, but the signal transduction pathway of its antioxidant effects is not very clear. In this study, we found that salidroside could attenuate hydrogen peroxide (H(2)O(2))-induced HL-7702 cell damage, inhibit H(2)O(2)-induced cytosolic free Ca2+ ([Ca2+]i) elevation, scavenge reactive oxygen species (ROS) and increase 3'-5'-cyclic adenosine monophosphate (cAMP) level in a dose-dependent manner, but it couldn't influence 3'-5'-cyclic guanosine monophosphate (cGMP) levels. Therefore, these results indicated that the antioxidant effects of salidroside were associated with down-regulation of [Ca2+]i, ROS occur via a cAMP-dependent pathway.
Asunto(s)
AMP Cíclico/metabolismo , Glucósidos/farmacología , Peróxido de Hidrógeno/farmacología , Fenoles/farmacología , Animales , Línea Celular , AMP Cíclico/biosíntesis , GMP Cíclico/biosíntesis , Relación Dosis-Respuesta a DrogaRESUMEN
Florfenicol is a new type of broad-spectrum antibacterial that has been used in veterinary clinics. It showed immunosuppressive activity on the immune responses to vaccination against foot-and-mouth disease virus (FMDV) serotype O in mice. In the present study, BALB/c mice were immunized subcutaneously with FMDV serotype O antigen on days 1 and 14. Beginning on day 21, mice were treated with a single daily oral dose of florfenicol (50, 100, and 200 mg/kg) for seven consecutive days. On day 28, blood samples were collected to analyze FMDV-specific immunoglobulin G (IgG), IgG1, and IgG2b antibodies, and splenocytes were harvested to assess lymphocyte proliferation, CD3(+) T- and CD19(+) B-lymphocyte subsets. The results presented here demonstrated that florfenicol not only significantly suppressed concanavalin A-, lipopolysaccharide-induced splenocyte proliferation but also decreased the percentage of CD19(+) B-cells in a dose-dependent manner and suppressed CD3(+) T-cell at high doses. Moreover, FMDV-specific IgG, IgG1, and IgG2b antibody levels in FMDV-immunized mice were reduced by florfenicol. These results suggested that florfenicol could suppress humoral and cellular immune responses to vaccination against foot-and-mouth disease (FMD) in mice.
Asunto(s)
Antibacterianos/farmacología , Virus de la Fiebre Aftosa/inmunología , Fiebre Aftosa/inmunología , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Tianfenicol/análogos & derivados , Vacunación , Vacunas Virales/farmacología , Animales , Anticuerpos Antivirales/inmunología , Linfocitos B/inmunología , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta Inmunológica , Fiebre Aftosa/prevención & control , Inmunoglobulina G/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Linfocitos T/inmunología , Tianfenicol/farmacología , Factores de Tiempo , Vacunas Virales/inmunologíaRESUMEN
8-gingerol is one of the principal components of ginger, which is widely used in China and elsewhere as a food, spice and herb. It shows immunosuppressive activity on the immune responses to ovalbumin (OVA) in mice. In the present study, we found that 8-gingerol suppressed lipopolysaccharide (LPS) and concanavalin A (ConA)-stimulated splenocyte proliferation in vitro. In vivo, 8-gingerol not only signiï¬cantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation (P < 0.05) but also decreased the percentage of CD19+ B cells and CD3+ T cell (P < 0.05) at high doses (50, 100 mg/kg). Moreover, OVA-speciï¬c IgG, IgG1 and IgG2b levels in OVA-immunized mice were reduced by 8-gingerol at doses of 50, 100 mg/kg. These results suggest that 8-gingerol could suppress humoral and cellular immune responses in mice. The mechanism might be related to direct inhibition of sensitized T and B lymphocytes.