RESUMEN
Rare-earth halide double perovskites (DPs) have attracted extensive attention due to their excellent optoelectronic performance. However, the correlation between luminescence performance, crystal structure, and temperature, as well as the inherent energy transfer mechanism, is not well understood. Herein, Lanthanide ions (Ln3+: Nd3+ or Dy3+) as the co-dopants are incorporated into Sb3+ doped Cs2NaYbCl6 DPs to construct energy transfer (ET) models to reveal the effects of temperature and energy levels of rare earth on luminescence and ET. The different excited state structures of Sb3+-Ln3+ doped Cs2NaYbCl6 DPs at different temperatures and relative positions of energy levels of rare earth synergistically determine the physical processes of luminescence. These multi-mode luminescent materials exhibit good performance in anti-counterfeiting, NIR imaging, and temperature sensing. This work provides new physical insights into the effects of temperature and energy levels of rare earth on the energy transfer mechanism and related photophysical process.
RESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common and lethal malignancies worldwide. Although DBF4-dependent kinase (DDK) complex composed of CDC7 kinase and its regulatory subunit DBF4 has been shown to be overexpressed in primary tumors and promotes tumor development, while its role and prognostic value in HCC remain largely unknown. In the present study, the expression of DBF4 and CDC7 and their relationship with clinical characteristics were comprehensively analyzed. METHODS: The mRNA expression profiles of HCC and the corresponding clinical data of HCC patients were downloaded from TCGA and GEO databases, respectively. The differences in DBF4 and CDC7 expression in tumor tissues and adjacent normal tissues were analyzed. HCC-derived tissue microarray (TMA) was used to evaluate and score the expression of CDC7 by immunohistochemistry (IHC) staining. The Kaplan-Meier method and the Cox regression method were used to analyze the relationship between overall survival and clinical characteristics of the patients. Gene set enrichment analysis (GSEA) was used to analyze the pathway enrichment of DBF4 and CDC7. RESULTS: DBF4 and CDC7 had similar expression patterns in HCC patients. Detailly, compared with adjacent tissues, both mRNA and protein of DBF4 and CDC7 were significantly higher in HCC, and their expression was positively correlated with AJCC_T stage, clinical stage and G stage (grade) of liver cancer patients, and higher DBF4 or CDC7 expression predicted a worse prognosis in HCC patients with shorter overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS) and progress-free survival (PFS). Cox regression analysis suggested that both DBF4 and CDC7 were independent risk factors for the prognosis of HCC patients in TCGA dataset. GSEA suggested that both DBF4 and CDC7 were positively correlated with cell cycle and DNA replication. Finally, the prognostic value of CDC7 was furtherly confirmed by TMA-based IHC staining results. CONCLUSIONS: Our study showed that DDK complex was significantly increased in HCC. Both DBF4 and CDC7 may be potential diagnostic and prognostic markers for HCC, and high expression of DDK members predicts a worse prognosis in patients with HCC, which may be associated with high tumor cell proliferation rate.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Carcinoma Hepatocelular/genética , Pronóstico , Neoplasias Hepáticas/genéticaRESUMEN
With the higher requirements of various tactical and technical indicators of the weapon systems, the current research on the ignition and combustion characteristics of different types of solid propellants is not comprehensive. In more complex and harsh environmental conditions, the pressure affects the ignition and combustion characteristics. Therefore, the paper studies the ignition and combustion characteristics of the modified double-base propellants (MDB propellants) and fuel-rich propellants (FR propellants) under low-pressure environment. Combining experiment and theory, the ignition delay time and burning rate of two kinds of solid propellants are compared and analyzed at low pressure by the laser ignition experimental device. The results displayed that the burning flames of the FR and MDB propellant presented evident V-shape and cylindrical, respectively. The flame brightness decreased with the decrease in pressure. With the increase of pressure and heat flux, the ignition delay time of the MDB propellant and the FR propellant decreased. By comparison, Model 2 of the ignition delay time was more effective for the estimation of the ignition delay time of the FR propellant. The experimental results are compared with the three burning rate models, which are the Vielle formula (Model 1), Summerfield formula (Model 2), and B-number burning rate formula (Model 3). The results showed the burning rate was more in accord with Model 3.
RESUMEN
This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.
Asunto(s)
Artritis Reumatoide , Medicamentos Herbarios Chinos , Sinoviocitos , Ratas , Animales , Metaloproteinasa 2 de la Matriz/metabolismo , Farmacología en Red , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Transducción de Señal , Fibroblastos , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg~(-1)), medium-(BGZM, 12.5 g·kg~(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.
Asunto(s)
Hígado , Agua , Ratas , Animales , Ratas Sprague-Dawley , FN-kappa B , Cirrosis Hepática , Ácidos y Sales Biliares , Peso Corporal , ARN MensajeroRESUMEN
Sepsis-induced inflammatory response leads to intestinal damage and secondary bacterial translocation, causing systemic infections and eventually death. Emodin is a natural anthraquinone derivative in many plants with promising bioactivities. However, the effects and mechanisms of emodin on sepsis-induced intestinal dysfunctions have not been well clarified yet. We found that emodin treatment suppressed the inflammatory response in the intestines of septic mice. Intestinal barrier function was also improved by emodin through enhancing ZO-1 and occludin expression, which prevented the secondary translocation of Escherichia coli. By proteome microarray investigation, JNK2 was identified as a direct target of emodin. In vitro study also showed that emodin inhibited LPS-induced inflammatory response in intestinal epithelial cells. Nuclear factors including NF-κB and AP-1 were further identified as downstream effectors of JNK2. Bioinformatic analysis based on 16s rRNA gene sequencing illustrated that emodin treatment significantly increased the alpha- and beta-diversity of gut microbiota in septic mice. Moreover, data according to functional prediction showed that emodin decreased the abundance of potential pathogenic bacteria in gut. Our findings have shown that emodin treatment prevented inflammatory induced barrier dysfunction and decreased the potential pathogenicity of lumen bacteria, reducing the hazard of lumen bacterial translocation during sepsis.
Asunto(s)
Emodina , Microbioma Gastrointestinal , Mucosa Intestinal , Sepsis , Animales , Emodina/uso terapéutico , Mucosa Intestinal/metabolismo , Lipopolisacáridos , Ratones , FN-kappa B/metabolismo , ARN Ribosómico 16S/metabolismo , Sepsis/tratamiento farmacológico , Sepsis/microbiologíaRESUMEN
BACKGROUND: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P < 0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).
Asunto(s)
Antifibrinolíticos , Artritis Reumatoide , Artroplastia de Reemplazo de Rodilla , Ácido Tranexámico , Administración Intravenosa , Anciano , Antifibrinolíticos/efectos adversos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/cirugía , Artroplastia de Reemplazo de Rodilla/efectos adversos , Pérdida de Sangre Quirúrgica/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Ácido Tranexámico/efectos adversosRESUMEN
Skeletal muscle atrophy is a common and serious complication of chronic kidney disease (CKD). Oxidative stress and autophagy are the primary molecular mechanisms involved in muscle atrophy. Calycosin, a major component of Radix astragali, exerts anti-inflammatory, anti-oxidative stress and anti-autophagy effects. We investigated the effects and mechanisms of calycosin on skeletal muscle atrophy in vivo and in vitro. 5/6 nephrectomy (5/6 Nx) rats were used as a model of CKD. We evaluated bodyweight and levels of serum creatinine (SCr), blood urea nitrogen (BUN) and serum albumin (Alb). H&E staining, cell apoptosis, oxidative stress biomarkers, autophagosome and LC3A/B levels were performed and evaluated in skeletal muscle of CKD rat. Calycosin treatment improved bodyweight and renal function, alleviated muscle atrophy (decreased the levels of MuRF1 and MAFbx), increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity and reduced malondialdehyde (MDA) levels in skeletal muscle of CKD rats. Importantly, calycosin reduced autophagosome formation, down-regulated the expression of LC3A/B and ATG7 through inhibition of AMPK and FOXO3a, and increased SKP2, which resulted in decreased expression of CARM1, H3R17me2a. Similar results were observed in C2C12 cells treated with TNF-α and calycosin. Our findings showed that calycosin inhibited oxidative stress and autophagy in CKD induced skeletal muscle atrophy and in TNF-α-induced C2C12 myotube atrophy, partially by regulating the AMPK/SKP2/CARM1 signalling pathway.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia/efectos de los fármacos , Isoflavonas/farmacología , Músculo Esquelético/patología , Atrofia Muscular/patología , Estrés Oxidativo/efectos de los fármacos , Proteína-Arginina N-Metiltransferasas/metabolismo , Insuficiencia Renal Crónica/patología , Animales , Apoptosis/efectos de los fármacos , Arginina/metabolismo , Peso Corporal/efectos de los fármacos , Línea Celular , Regulación hacia Abajo/efectos de los fármacos , Fibrosis , Histonas/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiopatología , Masculino , Metilación , Ratones , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Nefrectomía , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/fisiopatología , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfaRESUMEN
This publisher's note contains corrections to Opt. Lett.40, 5224 (2015).OPLEDP0146-959210.1364/OL.40.005224.
RESUMEN
Timosaponin B-II (TB-II; (25S)-26-(ß-D-glucopyranosyloxy)-3ß-[(2-O-ß-D-glucopyranosyl-ß-D-galactopyranosyl) oxy]-5ß-furostan-22-ol is extracted from Anemarrhena. Its anti-inflammation, anti-oxidation, and anti-asthma properties have been widely explored. However, its effect on the heart has not been reported. In this study, we used zebrafish as a research model to determine the effects of TB-II on the heart and its toxic and anti-inflammatory effects. To explore the cause of cardioprotective effects of TB-II, we used transgenic zebrafish with macrophages and neutrophils labeled with fluorescent protein. We found for the first time that TB-II had a protective effect on the zebrafish heart. It did not affect the survival and hatching rates of zebrafish embryos, indicating its low toxicity. Results showed that TB-II may have cardioprotective effects, which might be related to its anti-inflammatory effects.
Asunto(s)
Anemarrhena/química , Antiinflamatorios/farmacología , Cardiotónicos/farmacología , Saponinas/farmacología , Esteroides/farmacología , Animales , Animales Modificados Genéticamente , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Cardiotónicos/aislamiento & purificación , Cardiotónicos/toxicidad , Femenino , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Rizoma , Saponinas/aislamiento & purificación , Saponinas/toxicidad , Esteroides/aislamiento & purificación , Esteroides/toxicidad , Pez CebraRESUMEN
The analysis and utilization of clinical scientific research data is an effective means to promote the progress of diagnosis and treatment, and a key step in the development of medical sciences. During the epidemic of coronavirus disease 2019(COVID-19), how to transform the limited diagnostic data into clinical research resources has attracted much attention. Based on the low efficiency of data collection and extraction, the inconsistency of data analysis, the irregularity of data report and the high timeliness of data update during the epidemic, this paper briefly analyzed the background and reasons of data application under the current situation, and then discusses the problems and feasible solutions of clinical data applications under the epidemic situation and, more importantly, for future medical clinical research methods. We put forward several methodological suggestions: â gradually improve the medical big data model and establish the national medical health data center; â¡ improve the scientific research literacy of medical staff and popularize the basic skills and knowledge of GCP; ⢠promote a scientific, networked and shared data collection and management mode; ⣠use the mixed research method and collective analysis to improve the efficiency of clinical data analysis; ⤠pay attention to narration of the medical feelings and emphasize the humanistic data of clinical medicine. It is expected to promote the standardized and reasonable use of clinical scientific research data, the rigorous integration of expert opinions, and ultimately the development of big data for national health care.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , COVID-19 , Infecciones por Coronavirus/epidemiología , Humanos , Neumonía Viral/epidemiología , SARS-CoV-2RESUMEN
PURPOSE: Current clinical guidelines recommended the routine use of adjuvant chemotherapy for locally advanced rectal cancer (LARC) patients. However, the effects of adjuvant chemotherapy in patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy and radical surgery showed discrepancies in different investigations. METHODS: A systematic review and meta-analysis were conducted using PubMed, Embase and Web of Science databases. All original comparative studies published in English that were related to adjuvant versus non-adjuvant chemotherapy for LARC patients with pCR were included. RESULTS: A total of 6 studies based on 18 centres or databases involving 2948 rectal cancer patients with pCR (adjuvant group = 1324, non-adjuvant group = 1624) were included in our overall analysis. Based on our meta-analysis, LARC patients with pCR who received adjuvant chemotherapy showed a significantly improved overall survival (OS) when compared to patients with observation (HR = 0.65, 95% CI = 0.46-0.90, P = 0.01). In addition, investigations focused on this issue based on the National Cancer Database (NCDB) were systematically reviewed in our current study. Evidence from all three analyses demonstrated that LARC patients with clinical nodal positive disease that achieved pCR might benefit the most from additional adjuvant chemotherapy. CONCLUSION: Our meta-analysis indicated that adjuvant chemotherapy is associated with improved OS in LARC patients with pCR after neoadjuvant chemoradiotherapy and radical surgery.
Asunto(s)
Quimioradioterapia , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Quimioterapia Adyuvante , Humanos , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
BACKGROUND: To compare the surgical and long-term survival outcomes of laparoscopic and open total gastrectomy (OTG) for locally advanced gastric cancer (AGC). METHODS: We retrospectively evaluated 308 and 900 patients in pathological locally AGC who underwent laparoscopic total gastrectomy (LTG) or OTG between June 2008 and December 2014. We compared surgical and long-term outcomes between the two groups using propensity score matching method. RESULTS: The LTG group showed a longer operation time (261.42 vs. 171.00 min, P = 0.001), less blood loss (185.47 vs. 217.84 ml, P = 0.000), earlier time to first flatus (3.47 vs. 4.12 days, P = 0.000), earlier time to start liquid diet (3.76 vs. 4.27 days, P = 0.000), and shorter postoperative hospital stay (7.56 vs. 8.22 days, P = 0.007). The overall complication rate was 15.2% in the LTG group and 17.2% in the OTG (P = 0.503). No significant difference was observed in overall survival (OS) and disease-free survival (DFS) between LTG and OTG (60.5% vs. 57.1%, P = 0.337; 57.4% vs. 54.4%, P = 0.341). CONCLUSIONS: Compared to OTG, LTG provides surgical benefits and comparable survival outcomes for patients with locally AGC.
Asunto(s)
Gastrectomía/métodos , Laparoscopía , Neoplasias Gástricas/cirugía , Anciano , Pérdida de Sangre Quirúrgica , Supervivencia sin Enfermedad , Femenino , Gastrectomía/efectos adversos , Tracto Gastrointestinal/fisiopatología , Humanos , Laparoscopía/efectos adversos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias , Puntaje de Propensión , Recuperación de la Función , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: miR-135a is reduced in several cancers and has been suggested to mediate immune and inflammatory responses. However, the effect of miR-135a on inflammatory bowel diseases was obscure. This study firstly attempted to investigate the hypothesis that miR-135a alleviates dextran sodium sulfate (DSS)-induced inflammation in colonic cells and potential mechanisms are also studied. METHODS: Caco-2 and HT-29 cells in this study were treated with DSS, miR-135a mimic, and S3I-201, and then CKK-8 assay was used to test cell viability. Expressions of miR-135a, cytokines, and signal transducers and activators of transcription factors (STATs) were determined by RT-PCR. Also, cytokine productions were further tested by using ELISA kits. Activation or inactivation of STAT3 signal was validated by western blotting analysis. RESULTS: The results showed that DSS markedly downregulated miR-135a expression (P< 0.05) and induced inflammatory response in Caco-2 and HT-29 cells evidenced by the up regulations and productions of interleukin-1ß (IL-1ß) and tumor necrosis factor-É (TNF-É) (P< 0.05). Transfection with miR-135a mimic significantly alleviated DSS-induced upregulation and productions of IL-1ß and TNF-É in Caco-2 and HT-29 cells (P< 0.05). STATs were analyzed and miR-135a mimic treatment reversed STAT3 downregulation in DSS-challenged Caco-2 and HT-29 cells compared with the mimic control (P< 0.05). Also, STAT3 phosphorylation was inhibited in DSS-challenged Caco-2 cells and miR-135a mimic activated STAT3 signal (P< 0.05). S3I-201, an inhibitor of STAT3 signal, further used to inactivate STAT3 signal and the results showed that S3I-201 blocked the anti-inflammatory effect of miR-135a mimic on Caco-2 and HT-29 cells evidenced by the lowered expressions and productions of proinflammatory cytokines ((IL-1ß and TNF-É) (P< 0.05). CONCLUSION: Our results indicated that miR-135a alleviated DSS-induced inflammation and activated STAT3 signal in colonic cells. Inhibition of STAT3 reversed the anti-inflammatory function of miR-135a by regulating proinflammatory cytokines. Thus, STAT3 signal might serve, at least in part, as the potential mechanism of miR-135a-mediated anti-inflammatory effect in colonic cells.
Asunto(s)
Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/genética , Regulación hacia Abajo , Inflamación/complicaciones , Inflamación/genética , MicroARNs/genética , Factor de Transcripción STAT3/inmunología , Células CACO-2 , Neoplasias Colorrectales/inmunología , Sulfato de Dextran/efectos adversos , Regulación hacia Abajo/efectos de los fármacos , Células HT29 , Humanos , Inflamación/inducido químicamente , Inflamación/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , MicroARNs/inmunología , Factor de Transcripción STAT3/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND/AIMS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an ideal anti-tumor drug because it exhibits selective cytotoxicity against cancer cells. However, certain cancer cells are resistant to TRAIL, and the potential mechanisms are still unclear. The aim of this study was to reduce the resistance of colorectal cancer (CRC) cells to TRAIL. METHODS: Quantitative real-time PCR analysis was performed to detect the expression of microRNA-128 (miR-128) in tissues from patients with CRC and CRC cell lines. MTT assays were used to evaluate the effect of miR-128 on TRAIL-induced cytotoxicity against CRC cell lines. The distribution of death receptor 5 (DR5) and the production of reactive oxygen species (ROS) were detected by flow cytometry analysis. Western blot, flow cytometry, and luciferase reporter assays were performed to evaluate the potential mechanism and pathway of miR-128-promoted apoptosis in TRAIL-treated CRC cells. RESULTS: MiR-128 expression was downregulated in tumor tissues from patients with CRC as well as in CRC cell lines in vitro. The enforced expression of miR-128 sensitized CRC cells to TRAIL-induced cytotoxicity by inducing apoptosis. Mechanistically, bioinformatics, western blot analysis, and luciferase reporter assays showed that miR-128 directly targeted sirtuin 1 (SIRT1) in CRC cells. miR-128 overexpression suppressed SIRT1 expression, which promoted the production of ROS in TRAIL-treated CRC cells. This increase of ROS subsequently induced DR5 expression, and thus increased TRAIL-induced apoptosis in CRC cells. CONCLUSION: The combination of miR-128 with TRAIL may represent a novel approach for the treatment of CRC.
Asunto(s)
Apoptosis/efectos de los fármacos , MicroARNs/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Regiones no Traducidas 3' , Antineoplásicos/farmacología , Caspasa 8/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Sirtuina 1/antagonistas & inhibidores , Sirtuina 1/genética , Regulación hacia Arriba/efectos de los fármacosRESUMEN
An efficient method has been developed to identify meat species by using laser-induced breakdown spectroscopy (LIBS). To improve the accuracy and stability of meat species identification, multiplicative scatter correction (MSC) was adopted to first pretreat the spectrum for correction of spectrum scatter. Then the corrected spectra were identified by using the K-nearest neighbor (KNN) model. The results showed that the identification rate improved from 94.17% to 100% and the prediction coefficient of variance (CV) decreased from 5.16% to 0.56%. This means that the accuracy and stability of meat species identification using MSC and LIBS simultaneously improved. In light of the findings, the proposed method can be a valuable tool for meat species identification using LIBS.
Asunto(s)
Carne , Análisis Espectral/métodos , Rayos Láser , LuzRESUMEN
Diagnosing nasopharyngeal carcinoma (NPC) is a significant challenge because of the highly complex process. We proposed an approach to diagnose NPC serum using a combination of hyperspectral imaging and weight-based principal component analysis. Samples were prepared by pressing boric acid into pellets for use as the sera substrate. The sera, collected from 100 healthy volunteers and 60 NPC patients, was dripped onto the surface of the substrate for hyperspectral imaging. The characteristic spectral bands were selected based on the variable weight obtained from a support vector machine (SVM) model, using principal component analysis (PCA) to reduce the dimension in the extracted bands. Obtained results show that the accuracy rate, sensitivity, and specificity between the NPC sera and the sera of the healthy controls reached extremely high levels of 99.15%, 98.79%, and 99.36%, respectively. For the model's consistency evaluation, we found that the Kappa and area under the curve (AUC) of the receiver operating characteristic (ROC) curve were 0.99 and 0.98, respectively. These results suggest that the developed approach could serve as a noninvasive diagnostic and screening tool for highly accurate and consistent detection of NPC. Hence, a combination of hyperspectral imaging (HSI) and a weighted principal component analysis (WPCA)-SVM model represents a powerful and promising tool for NPC diagnosis.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Nasofaríngeo/diagnóstico , Análisis de Componente Principal , Espectrofotometría Infrarroja/métodos , Humanos , Carcinoma Nasofaríngeo/sangre , Curva ROC , Sensibilidad y Especificidad , Máquina de Vectores de SoporteRESUMEN
BACKGROUND: Cervical cancer (CC) is one of the most common cancers among females worldwide. Spindle and kinetochore-associated complex subunit 3 (SKA3), located on chromosome 13q, was identified as a novel gene involved in promoting malignant transformation in cancers. However, the function and underlying mechanisms of SKA3 in CC remain unknown. Using the Oncomine database, we found that expression of SKA3 mRNA is higher in CC tissues than in normal tissues and is linked with poor prognosis. METHODS: In our study, immunohistochemistry showed increased expression of SKA3 in CC tissues. The effect of SKA3 on cell proliferation and migration was evaluated by CCK8, clone formation, Transwell and wound-healing assays in HeLa and SiHa cells with stable SKA3 overexpression and knockdown. In addition, we established a xenograft tumor model in vivo. RESULTS: SKA3 overexpression promoted cell proliferation and migration and accelerated tumor growth. We further identified that SKA3 is involved in regulating cell cycle progression and the PI3K/Akt signaling pathway via RNA-sequencing (RNA-Seq) and gene set enrichment analyses. Western blotting results revealed that SKA3 overexpression increased levels of p-Akt, cyclin E2, CDK2, cyclin D1, CDK4, E2F1 and p-Rb in HeLa cells. Additionally, the use of an Akt inhibitor (GSK690693) significantly reversed the cell proliferation capacity induced by SKA3 overexpression in HeLa cells. CONCLUSIONS: We suggest that SKA3 overexpression contributes to CC cell growth and migration by promoting cell cycle progression and activating the PI3K-Akt signaling pathway, which may provide potential novel therapeutic targets for CC treatment.
RESUMEN
A chemotherapeutic drug exerts favorable antitumor activity and simultaneously exhibits expectable inhibition on wound healing process. Phenanthroimidazole derivatives possess potent anticancer activity. However, only a few studies focused on the discovery of its potential effects on promoting tissue regeneration. In this study, four novel phenanthroimidazole derivatives were synthesized and characterized, and they exhibited evident inhibition on different tumor cells; compound 3 is the most active one. Moreover, 3 can promote wound healing of zebrafish in a dose-dependent manner. Further study demonstrated that 3 promoted the recruitment of inflammatory cells, formation of angiogenesis, and generation of reactive oxygen species and also influenced the motor behavior of zebrafish. Results indicated that 3 can accelerate the occurrence of pro-inflammation, angiogenesis, oxidative stress, and innervation, which play key roles in the facilitation of wound healing. Therefore, 3 can act as a bifunctional drug in inhibiting tumor and promoting tissue regeneration.
Asunto(s)
Aletas de Animales/efectos de los fármacos , Antineoplásicos/farmacología , Imidazoles/farmacología , Regeneración/efectos de los fármacos , Aletas de Animales/fisiología , Animales , Animales Modificados Genéticamente , Antineoplásicos/toxicidad , Conducta Animal/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Embrión no Mamífero/irrigación sanguínea , Embrión no Mamífero/efectos de los fármacos , Proteínas Fluorescentes Verdes/genética , Humanos , Imidazoles/toxicidad , Inflamación/inmunología , Larva/efectos de los fármacos , Larva/inmunología , Locomoción/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Especies Reactivas de Oxígeno/inmunología , Cicatrización de Heridas/efectos de los fármacos , Pez Cebra/genéticaRESUMEN
BACKGROUND: There still remains controversy for the choice of resection extent for gastric cancer involving the middle-third of the stomach. The aim of this study was to compare the technical feasibility and long-term outcomes of laparoscopy-assisted distal gastrectomy (LADG) versus laparoscopy-assisted total gastrectomy (LATG) for middle-third advanced gastric cancer (AGC) and to determine which is the optimal surgical procedure. METHODS: For this study, clinical data for 379 patients who underwent LADG or LATG with D2 lymph node dissection between April 2005 and June 2014 were analyzed retrospectively. The short- and long-term outcomes were compared between the propensity score-matched groups. RESULTS: The LADG group had a significantly shorter operating time (212.74 vs. 241.79 min, P < 0.001), less estimated blood loss (114.38 vs. 181.51 ml, P = 0.000), shorter first flatus and postoperative hospital stay. Additionally, the total cost of hospitalization was significantly higher in the LATG group than LADG group (71187.58 vs. 65783.25 RMB, P = 0.000). There were no significant differences in postoperative complications rate between the LADG group and the LATG group. The 5-year overall survival (OS) rates were 64.4% in the LADG group and 61.0% in the LATG group (P = 0.548). The resection extent was not an independent prognostic factor for the OS. CONCLUSIONS: LADG with D2 nodal dissection is a feasible treatment strategy for middle-third AGC with better short-term outcomes and similar long-term survival rates compared with LATG. We recommended that DG should be the optimal surgical procedure for middle one-third AGC under the premise of negative proximal resection margin.