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Objective: To explore the mechanisms of the TGF-ß1/Smad and NF-κB pathways in the effect of berberine (BBR) on colon cancer epithelial-mesenchymal transition (EMT) and their regulatory relationships with microRNAs (miRNAs). Methods: TGF-ß1 was used to induce EMT in normal colon epithelial HCoEpiC cells and colon cancer HT29 cells in vitro. After BBR intervention, the expression of EMT-related markers and the major molecules involved in the TGF-ß1/Smad and NF-κB pathways were detected via western blotting. Cell migration was detected via wound healing assays. SMAD2 and NF-κB p65 were overexpressed and transfected into cells, and the inhibitors SB431542 and BAY 11-7082 were added to block the TGF-ß1/Smad and NF-κB pathways, respectively. The mRNA expression levels of related microRNA genes were detected by using RTâPCR. Results: Treatment with 10 ng/ml TGF-ß1 for 72 h significantly induced EMT in HCoEpiC and HT29 cells, which was repressed by BBR. BBR significantly inhibited the TGF-ß1-induced migration of HCoEpiC and HT29 cells and the TGF-ß1-promoted expression of p-Smad2/3, NF-κB p65, and p-IκBα. Compared to those in the group treated with TGF-ß1, the expression of NF-κB p65 and p-Smad2 in the group treated with NF-κB pathway inhibitor BAY 11-7082 was decreased (P < 0.05), and TGF-ß1 signalling inhibitor SB431542 significantly reduced the expression of NF-κB p65 (P < 0.05). Overexpression of NF-κB p65 and SMAD2 in HT29 cells decreased the expression of E-cadherin and caused a relative increase in N-cadherin. BBR mediated the expression profile of microRNAs in TGF-ß1-induced HCoEpiC cells, but this pattern differed from that in HT29 cells. SB431542 and BAY 11-7082 significantly reduced the mRNA level of miR-1269a in HCoEpiC and HT29 cells (P < 0.05). Overexpressed NF-κB p65 and SMAD2 increased the mRNA level of miR-1269a in both cell lines; however, this increase was significantly lower than that in the TGF-ß1 treatment group (P < 0.05). Conclusion: BBR can significantly inhibit TGF-ß1-induced EMT in normal and cancerous colon epithelial cells through the inhibition of the TGF-ß1/Smad and NF-κB p65 pathways. TGF-ß1/Smads can promote the NF-κB p65 pathway, which is a common target of miR-1269a, and can partially regulate the expression of miR-1269a.
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Objective: In this study, we aimed to perform a network meta-analysis to compare the effectiveness of NAs in decreasing the reactivation of HBV, reducing chemotherapy disruption, and improving survival in oncology patients. Methods: Relevant randomized controlled trials (RCT) evaluating the impact of NAs in HBV infected-related oncology patients were retrieved from electronic databases. The outcome indicators included reactivation rate, survival rate of 1 to 3 years after treatment, and chemotherapy disruption rate. The studies were evaluated for bias using the RCT risk of bias assessment tool recommended in the Cochrane Handbook. The risk ratio (RR) was used to compare the outcome indicators for the anti-viral treatment, and the surface under the cumulative ranking curves (SUCRA) was used to identify the optimal therapeutic regime. Results: A total of 67 trials containing 5722 patients were included in this study. Regarding the reduction of reactivation rate, entecavir, lamivudine, adefovir alone were less effective than the combination of lamivudine and entecavir (94.9%), with RR values ranging from 3.16 to 3.73. However, based on SUCRA, the efficacy of telbivudine (80.3%) and the combination of lamivudine and adefovir dipivoxil (58.8%) were also acceptable. Entecavir (RR values ranging from 1.25 to 1.50) and lamivudine (RR values ranging from 1.27 to 1.35) can prolong the survival rate of patients at 1-3 years, and were better than adefovir dipivoxil in the comparison of 1-year survival rate. The RR values were 1.18 and 1.19, respectively. And entecavir 's ranking in SUCRA was more stable. Entecavir, lamivudine, and tenofovir all reduced chemotherapy interruption rates compared with no antiviral therapy, especially for tenofovir. Conclusions: Current evidence shows that lamivudine combined with entecavir, telbivudine, and lamivudine combined with adefovir dipivoxil were the most effective in preventing virus reactivation in HBV infected-related cancer patients treated with chemotherapy. Entecavir had the most stable effect on survival, while tenofovir had the best impact on reducing the chemotherapy disruption rate. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions. Systematic review registration: PROSPEROI [https://www.crd.york.ac.uk/PROSPERO/index.php], identifier CRD4202250685.
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Gallbladder cancer has high incidence and mortality and a low early diagnosis rate and requires rapid and efficient diagnosis. Herein, carboxyl/amino functionalized polymer dots (Pdots) were designed to enhance cellular internalization and tumor accumulation. The prepared Pdots were 40-50 nm in diameter, contained no toxic metal, exhibited long circulation time and high stability, and produced strong NIR emission and photoacoustic signals. Different cellular uptake and distribution of functionalized Pdots in eight gallbladder cell lines were quantitatively investigated using flow cytometry and super-resolution microscopy. In vivo NIR fluorescence imaging showed that the functional Pdots had high accumulation in the tumor after 30 minutes of injection and remained there for up to 6 days. In addition, photoacoustic imaging found that the abundant blood vessels around the tumor microenvironment and Pdots entered the tumor through the blood vessels. Furthermore, a high heterogeneity of vascular networks was visualized in real-time and high resolution by probe-based confocal laser endomicroscopy imaging. These results offer a new avenue for the development of functional Pdots as a probe for multi-modal and multi-scale imaging of gallbladder cancer in small animals.
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Neoplasias de la Vesícula Biliar , Técnicas Fotoacústicas , Puntos Cuánticos , Animales , Diagnóstico por Imagen , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Polímeros , Semiconductores , Microambiente TumoralRESUMEN
PURPOSE: Probe-based confocal laser endomicroscopy (pCLE) is a novel technique allowing real-time and high-resolution imaging in vivo. It provides microscopic images and increases the penetration depth of tissues compared with conventional white light endoscopy. The aim of the present study was to track ovarian cancer cells in organs by fluorescent polymer dots based on pCLE. PROCEDURES: SKOV3-mCherry cells were incubated with polymer dots for 24 h in a serum-free culture medium. Labeled cells were administrated to nude mice via intravenous, intraperitoneal, and lymph node injection. The fluorescent signals of labeled cells in organs were observed by pCLE. Furthermore, the results were confirmed by frozen section analysis. RESULTS: pCLE displayed fluorescence signals of labeled cells in the vessels of organs. Besides, the accumulations of labeled cells visualized in detoxification organs like the spleen and kidney were increased with time. CONCLUSIONS: In this article, we present a real-time and convenient method for tracking SKOV3-mCherry in living mice by combined fluorescent polymer dots with pCLE.
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Rastreo Celular , Endoscopía , Rayos Láser , Microscopía Confocal , Sondas Moleculares/química , Polímeros/química , Animales , Línea Celular Tumoral , Fluorescencia , Imagenología Tridimensional , Ratones Endogámicos BALB C , Ratones Desnudos , Especificidad de Órganos , Polímeros/síntesis químicaRESUMEN
Noninvasive, repeated, and high-resolution imaging of the lymphatic vascular system plays an important role in studying the development and function of lymphatics. However, conventional imaging modality such as magnetic resonance imaging (MRI) and X-ray lymphangiography shows insufficient temporal and spatial resolution and can only visualize large lymphatic vessels. Herein, we developed polymer dots as a novel lymphatic agent for simultaneously imaging the lymphatic capillary plexus and collecting lymphatic vessels in living mice/rats at a fast temporal resolution and high spatial resolution by combination with probe-based confocal laser endomicroscopy (pCLE). The imaging effect was verified by whole-body near-infrared fluorescence and photoacoustic imaging as well as ex vivo two-photon microscope imaging. Our study provides a novel approach for using polymer dots for high-resolution lymphatic vascular imaging in small animals.
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In vivo cell tracking can provide information on cell migration and accumulation in the organs. Here, both folate and amino modified polymer dots were synthesized and screened for in vitro and in vivo tracking of macrophage Ana-1 cells. Flow cytometry analysis demonstrated that prepared polymer dots showed cellular uptake of approximately 98% within a short incubation time of 2 h, and these polymer dots maintained a cell labeling rate over 97% after 2 d. Moreover, a CCK-8 assay suggested that these polymer dots increased Ana-1 cell viabilities up to 110% at concentrations from 5 to 50 µg mL-1. Furthermore, the in vivo real time imaging of labelled Ana-1 cells in the alveolus of lung and lymph nodes were clearly detected by probe-based confocal laser endomicroscopy (pCLE). This study demonstrates a unique approach using polymer dots for real-time high resolution tracking of macrophage cells in deep organs and the lymphatic system.
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Brown adipose tissue (BAT) has been identified as a promising target for the treatment of obesity, diabetes, and relevant metabolism disorders because of the adaptive thermogenesis ability of this tissue. Visualizing BAT may provide an essential tool for pathology study, drug screening, and efficacy evaluation. Owing to limitations of current nuclear and magnetic resonance imaging approaches for BAT detection, fluorescence imaging has advantages in large-scale preclinical research on small animals. Here, fast BAT imaging in mice is conducted based on polymer dots as fluorescent probes. As early as 5 min after the intravenous injection of polymer dots, extensive fluorescence is detected in the interscapular BAT and axillar BAT. In addition, axillar and inguinal white adipose tissues (WAT) are recognized. The real-time in vivo behavior of polymer dots in rodents is monitored using the probe-based confocal laser endomicroscopy imaging, and the preferred accumulation in BAT over WAT is confirmed by histological assays. Moreover, the whole study is conducted without a low temperature or pharmaceutical stimulation. The imaging efficacy is verified at the cellular, histological, and whole-body levels, and the present results indicate that fluorescent polymer dots may be a promising tool for the visualization of BAT in living subjects.