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BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma worldwide. Novel treatment strategies are still needed for refractory or relapsed DLBCL. OBJECTIVE: The present study aimed to systematically explore the potential targets and molecular mechanisms of matrine in the treatment of DLBCL. METHODS: Potential matrine targets were collected from multiple platforms. Microarray data and clinical characteristics of DLBCL were downloaded from publicly available databases. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were applied to identify the hub genes of DLBCL using R software. Then, the shared target genes between matrine and DLBCL were identified as the potential targets of matrine against DLBCL. The least absolute shrinkage and selection operator (LASSO) algorithm was used to determine the final core target genes, which were further verified by molecular docking simulation and receiver operating characteristic (ROC) curve analysis. Functional analysis was also performed to elucidate the potential mechanisms. RESULTS: A total of 222 matrine target genes and 1269 DLBCL hub genes were obtained through multiple databases and machine learning algorithms, respectively. From the nine shared target genes of matrine and DLBCL, five final core target genes, including CTSL, NR1H2, PDPK1, MDM2, and JAK3, were identified. Molecular docking showed that the binding of matrine to the core genes was stable. ROC curves also suggested close associations between the core genes and DLBCL. Additionally, functional analysis showed that the therapeutic effect of matrine against DLBCL may be related to the PI3K-Akt signaling pathway. CONCLUSION: Matrine may target five genes and the PI3K-Akt signaling pathway in DLBCL treatment.
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BACKGROUND: Speckle-type POZ protein(SPOP), a substrate adaptor of Cul3 ubiquitin ligase, plays crucial roles in solid neoplasms by promoting the ubiquitination and degradation of substrates. Limited studies have shown that SPOP is overexpressed in human renal cell carcinoma (RCC) tissue. However, the exact role of SPOP in RCC remains unclear and needs to be further elucidated. The present study showed that SPOP was expressed at different levels in different RCC cell lines. The purpose of this study was to explore the roles of SPOP in the biological features of RCC cells and the expression levels of SPOP in human tissue microarray (TMA) and kidney tissues. METHODS: Here, SPOP was overexpressed by lentiviral vector transfection in ACHN and Caki-1 cells, and SPOP was knocked down in Caki-2 cells with similar transfection methods. The transfection efficiency was evaluated by quantitative PCR and western blotting analyses. The role of SPOP in the proliferation, migration, invasion and apoptosis of cell lines was determined by the MTT, wound-healing, transwell and flow cytometry assays. Moreover, the cells were treated with different drug concentrations in proliferation and apoptosis assays to investigate the effect of sunitinib and IFN-α2b on the proliferation and apoptosis of SPOP-overexpressing cells and SPOP-knockdown RCC cells. Finally, immunohistochemical staining of SPOP was performed in kidney tissues and TMAs, which included RCC tissues and corresponding adjacent normal tissues. RESULTS: Overexpression of SPOP inhibited cell proliferation, migration and invasion and increased cell apoptosis. Interestingly, sunitinib and IFN-α2b at several concentrations increased the proliferation inhibitory rate and total apoptosis rate of cells overexpressing SPOP. The findings of the present study showed that the SPOP protein was significantly expressed at low levels in most clear cell RCC (ccRCC) tissues and at relatively high levels in the majority of adjacent normal tissues and kidney tissues. Kaplan-Meier survival analysis showed that there was no statistically significant difference in cumulative survival based on the data of different SPOP expression levels in TMA and patients. CONCLUSIONS: In contrast to previous studies, our findings demonstrated that overexpression of SPOP might suppress the progression of RCC cells, which was supported by cell experiments and immunohistochemical staining. SPOP could be a potential tumour inhibitor in RCC.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genéticaRESUMO
Background: Emergence agitation (EA) is common in patients after general anesthesia (GA) and is associated with poor outcomes. Patients with thoracic surgery have a higher incidence of EA compared with other surgery. This study aimed to investigate the impact of pre-anesthetic butorphanol infusion on the incidence of EA in patients undergoing thoracic surgery with GA. Materials and methods: This prospective randomized controlled trial (RCT) was conducted in 20 tertiary hospitals in China. A total of 668 patients undergoing elective video-assisted thoracoscopic lobectomy/segmentectomy for lung cancer were assessed for eligibility, and 620 patients were enrolled. In total, 296 patients who received butorphanol and 306 control patients were included in the intention-to-treat analysis. Patients in the intervention group received butorphanol 0.02 mg/kg 15 min before induction of anesthesia. Patients in the control group received volume-matched normal saline in the same schedule. The primary outcome was the incidence of EA after 5 min of extubation, and EA was evaluated using the Riker Sedation-Agitation Scale (RSAS). The incidence of EA was determined by the chi-square test, with a significance of P < 0.05. Results: In total, 296 patients who received butorphanol and 306 control patients were included in the intention-to-treat analysis. The incidence of EA 5 min after extubation was lower with butorphanol treatment: 9.8% (29 of 296) vs. 24.5% (75 of 306) in the control group (P = 0.0001). Patients who received butorphanol had a lower incidence of drug-related complications (including injecting propofol pain and coughing with sufentanil): 112 of 296 vs. 199 of 306 in the control group (P = 0.001) and 3 of 296 vs. 35 of 306 in the control group (P = 0.0001). Conclusion: The pre-anesthetic administration of butorphanol reduced the incidence of EA after thoracic surgery under GA. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=42684], identifier [ChiCTR1900025705].
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Background: Clear cell renal cell carcinoma (ccRCC) is the most common pathological type of renal cell carcinoma. Tetratricopeptide repeat domain 21A (TTC21A), known as a component of intraflagellar transport complex A which is essential for the function of cilia, However, the role of TTC21A remains unclear in ccRCC. For the first time, we explore the role and potential mechanism of TTC21A in ccRCC based on multiple databases. Methods: TTC21A expression across all TCGA tumor was analyzed via Tumor Immune Estimation Resource (TIMER) site. The correlation between TTC21A and clinicopathologic characteristics of ccRCC was analyzed with TCGA database. The diagnostic and prognostic value of TTC21A was evaluated by receiver operation characteristic curve, Kaplan-Meier plotter and Cox regression respectively. Moreover, functional enrichment analysis of TTC21A and the co-expression genes were performed by Gene Set Enrichment Analysis. The correlation of TTC21A and immune infiltration were evaluated by single sample Gene Set Enrichment Analysis. Results: Pan-cancer analysis indicated that TTC21A was highly expressed in ccRCC and other cancer. In addition, elevated expression of TTC21A was associated with worse overall survival in ccRCC patients. Functional enrichment analysis showed that TTC21A and the co-expressed genes enriched in glucose metabolism and energy metabolism. Moreover, TTC21A expression was associated with infiltrating levels of dendritic cell, nature killer cell and other immune marker sets. Conclusion: The results of analysis indicate that expression of TTC21A is associated with poor prognosis and immune infiltrating in ccRCC, which suggested TTC21A might be used as a potential predictor and target of treatment in ccRCC.
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BACKGROUND: Phthalates are commonly used in variety of plastic products. Previously it has been revealed that di (2-ethylhexyl) phthalate (DEHP), as the most common member of the class of phthalates, may disturb cholesterol homeostasis and deregulate the inflammatory response, and leading to accelerate the atherosclerosis process. In this regard, the aim of the current study is to explore the underlying mechanism of DEHP-induced atherosclerosis through the increasing of foam cell formation and Vascular Smooth Muscle Cells (VSMCs) damage via the interaction of long-non coding RNA (GAS5) and miR-145-5p. METHODS: ApoE-/- mice were used to evaluate the in vivo study. RAW264.7 and VSMCs were used to evaluate the effect of DEHP on formation of foam cell, cell proliferation, and cell damage in vitro. Animals were treated with DEHP (5% w/w of food) orally and cells were treated with medium containing of 100 µM DEHP; qRT-PCR, Western blotting, flowcytometry, IHC, oil red O, BODIPY, and autophagic vacuoles assay were used to evaluate the effect of DEHP on formation of atherosclerosis. RESULTS: DEHP significantly accelerated the formation of atherosclerosis in mice and alter the lipid profile in mice. In addition, after treating VSMCs with DEHP, GAS5 was significantly up-regulated and miR-145-5p was down-regulated. In VSMCs treated with DEHP, we observed that GAS5 could be used as the competing endogenous RNA (ceRNA) of miR-145-5p to regulate the proliferation and apoptosis of VSMCs; and the expression of GAS5 was correlated with the expression of miR-145-5p. DEHP increased the ox-LDL uptake by macrophage and increasing the formation of foam cells. Besides, GAS5 knocking down reversed the effect of DEHP on foam cell formation and ox-LDL uptake. CONCLUSION: DEHP could accelerate the atherosclerosis process through increasing VSMCs damage and formation of macrophage foam cell by increasing lipid uptake though down regulating lncRNA GAS5 and altering in regulation of miR-145-5p.
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Aterosclerose , Dietilexilftalato , MicroRNAs , RNA Longo não Codificante , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Apolipoproteínas E/farmacologia , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Movimento Celular , Proliferação de Células , Colesterol/metabolismo , Dietilexilftalato/metabolismo , Células Espumosas/metabolismo , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , Macrófagos/metabolismo , Camundongos , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Ácidos Ftálicos , Plásticos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: As the most common malignant tumor of primary renal tumor, renal cell carcinoma (RCC) is the highly invasive disease with high mortality. AKT is a serine/threonine kinase that play a critical role in the phosphoinositide 3-kinase (PI3K) signaling pathway, and it is an attractive target for RCC treatment. The aim of present study was to investigate the effect of AKT silence on malignant behavior of renal cell carcinoma cells. METHODS: AKT expression was quantified by immunohistochemistry in tumor tissues and normal tissues. The human RCC cell lines Caki-2 cell were chosen for this study. The optimal silencing siRNA was subsequently selected by RT-qPCR and western blot. The effect of AKT silence on RCC cells was investigated by CCK8 assay, transwell assay, scratch test and flow cytometry. The AKT1 expression in human renal cell carcinoma tissue was detected by immunohistochemical staining. RESULTS: The AKT in Caki-2 cells was silenced successfully. The results shown AKT silence could inhibit cell proliferation, invasion, and, migration. In addition, AKT silence could promote Caki-2 cell apoptosis with prevention of RCC cells move from G1 phase to S phase. Immunohistochemical staining revealed significant difference of expression of AKT1 in RCC tissues and normal renal tissues. Taken together, AKT family members might involve in malignant growth of RCC, and might be a potential therapeutic target. CONCLUSION: Our data show that AKT silence inhibited cell proliferation, invasion, and, migration of Caki-2 cell, and promoted Caki-2 cell apoptosis. Moreover, AKT silence prevented RCC cells move from G1 phase to S phase. Therefore, AKT may act as an effective therapeutic target for RCC.
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Carcinoma de Células Renais , Neoplasias Renais , Proteínas Proto-Oncogênicas c-akt , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Neoplasias Renais/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Subsequently to the publication of the above article, the authors have realized that they inadvertently included images of the same mice in Figs. 7A [the Negative Control (NC) experiment] and 8A [the 5B3CT + Docetaxel (10 mg/kg) experiment]. After having consulted their original data, the authors have realized that these mice were correctly shown in the paper for the experiments portrayed in Fig. 7A; therefore, the corrected version of Fig. 8 is shown on the next page, showing the mice pertaining to the 5B3CT + Docetaxel (10 mg/kg) experiment in Fig. 8A. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologize to the readership for any inconvenience caused. [Oncology Reports 46: 196, 2021; DOI: 10.3892/or.2021.8147].
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Background: The reproducibility of radiomic features is essential to lung cancer detection. This study aimed to investigate the reproducibility of radiomic features of pulmonary nodules between low-dose computed tomography (LDCT) and conventional-dose computed tomography (CDCT). Methods: A total of 105 patients with 119 pulmonary nodules [39 ground-glass nodules (GGNs) and 80 solid nodules] who underwent LDCT and CDCT were retrospectively studied between September 2019 and November 2020. Pulmonary nodules were manually segmented and 1,125 radiomic features (shape, first-order intensity, texture, wavelet, and Laplacian of the Gaussian features) were extracted from both LDCT and CDCT images. The concordance correlation coefficient (CCC) was used to evaluate the reproducibility of these radiomic features. Results: Of the 1,125 radiomic features considered, 35.5% (399 of 1,125) and 41.5% (467 of 1,125) were reproducible (CCC ≥0.85) for GGNs and solid nodules, respectively. The intensity, texture, and wavelet features of solid nodules were more reproducible than those of GGNs. The mean CCC values for intensity and texture features of solid nodules were of 0.85 and above, whereas the mean values for those of GGNs were of less than 0.85. After Gaussian kernel (σ =2) preprocessing, the CCC of intensity and texture features of GGNs improved from 0.77 to 0.90, and 84.9% (79 of 93) of the radiomic features were reproducible (mean CCC increase from 0.84±0.13 to 0.92±0.08 for intensity features, and from 0.75±0.15 to 0.89±0.11 for texture features). Wavelet features had the lowest CCCs for both GGNs and solid nodules. Conclusions: The majority of the radiomic feature classes of solid pulmonary nodules have a high level of reproducibility between LDCT and CDCT. However, LDCT should not be used as an alternative to CDCT in the radiomic study of GGNs.
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Prostate cancer (PCa) is the most common cancer type in men worldwide. Currently, the management of metastatic PCa (mPCa) remains a challenge to urologists. The analysis of hub genes and pathways may facilitate the understanding of the molecular mechanism of PCa. In the present study, to identify the hub genes in the mPCa, the three datasets GSE3325, GSE6919 and GSE38241 were downloaded from the platform of the Gene Expression Omnibus and function enrichment analysis of differentially expressed genes (DEGs) was performed. A total of 168 DEGs were obtained and the DEGs were significantly enriched in 'cell junction' and 'cell adhesion', among others. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that DEGs were enriched in three pathways including 'focal adhesion', 'renal cell carcinoma' and 'Hippo signaling pathway'. The results of the proteinprotein interaction network revealed that the hub genes in mPCa were separately PTEN, Rac GTPaseactivating protein 1, protein regulator of cytokinesis 1, PDZ binding kinase, centromereassociated protein E, NUF2 component of NDC80 kinetochore complex, TPX2 microtubule nucleation factor, SOX2, CD44 and ubiquitinlike with PHD and ring finger domains 1. As a hub gene, CD44 was differentially expressed in PCa, as determined by Oncomine analysis. Further experiments in vivo demonstrated that SB3CT, a selective matrix metalloproteinase inhibitor that has been reported to block CD44 cleavage and inhibit the downstream signaling pathway, suppressed the tumorigenicity of PCa cells by decreasing the expression levels of pyruvate dehydrogenase kinase 1 and 6phosphofructo2kinase/fructose2,6biphosphatase 4. Moreover, the combination therapy with SB3CT and docetaxel was more effective in inhibiting PCa compared with monotherapy. In conclusion, the identification of DEGs and the in vivo experimental results helped to elucidate the molecular mechanisms of PCa and provided a potential strategy for the treatment of PCa.
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Regulação Neoplásica da Expressão Gênica , Receptores de Hialuronatos/biossíntese , Neoplasias da Próstata/metabolismo , Animais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células , Biologia Computacional , Bases de Dados Genéticas , Progressão da Doença , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Receptores de Hialuronatos/genética , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Transplante de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Próstata/genética , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genéticaRESUMO
The early detection of blood in urine (hematuria) can play a crucial role in the treatment of serious diseases (e.g., infections, kidney disease, schistosomiasis, and cancer). Therefore, the development of low-cost portable biosensors for blood detection in urine has become necessary. Here, we designed an ultrasensitive whole-cell bacterial biosensor interfaced with an optoelectronic measurement module for heme detection in urine. Heme is a red blood cells (RBCs) component that is liberated from lysed cells. The bacterial biosensor includes Escherichia coli cells carrying a heme-sensitive synthetic promoter integrated with a luciferase reporter (luxCDABE) from Photorhabdus luminescens. To improve the bacterial biosensor performance, we re-engineered the genetic structure of luxCDABE operon by splitting it into two parts (luxCDE and luxAB). The luxCDE genes were regulated by the heme-sensitive promoter, and the luxAB genes were regulated by either constitutive or inducible promoters. We examined the genetic circuit's performance in synthetic urine diluent supplied with heme and in human urine supplied with lysed blood. Finally, we interfaced the bacterial biosensor with a light detection setup based on a commercial optical measurement single-photon avalanche photodiode (SPAD). The whole-cell biosensor was tested in human urine with lysed blood, demonstrating a low-cost, portable, and easy-to-use hematuria detection with an ON-to-OFF ratio of 6.5-fold for blood levels from 5 × 104 to 5 × 105 RBC per mL of human urine.
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Técnicas Biossensoriais/métodos , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Hematúria/diagnóstico , Heme/urina , Luciferases Bacterianas/genética , Photorhabdus/enzimologia , Redes Reguladoras de Genes , Genes Bacterianos , Genes Reporter , Heme/genética , Humanos , Medições Luminescentes , Microrganismos Geneticamente Modificados , Óperon , Regiões Promotoras GenéticasRESUMO
OBJECTIVE: The patency and quality of transplanted great saphenous vein (GSV) can seriously influence the physical state and life quality of patients who accepted the coronary artery bypass grafting (CABG). Quercetin is known for antioxidant, antithrombotic, anti-inflammatory, and antitumor properties. In this study, we examined the protection of quercetin to the great saphenous vein from oxidative and inflammatory damage. METHODS: The GSVs were collected from 15 patients undergoing CABG and cultured. Treated the veins by H2O2 and detected the NO, SOD, and MDA content by the relevant kits to explore the quercetin protection against oxidative damage. Then, for another group of GSVs, sheared them and detected the inflammatory cytokines, such as IL-6, TNFα, CCL20, PCNA, and VEGF. Collect the veins for H&E staining and PCNA and VEGF immunofluorescent staining. RESULTS: Pretreatment by quercetin reduced the production of NO and MDA induced by H2O2, and increased SOD activity. Quercetin also supressed the mRNA expressions of IL-6, TNFα after mechanical damage and had no influence on CCL20 and VEGF. Consistent with the lower expression of PCNA treated by quercetin, the vein intima was thinner. CONCLUSION: These results demonstrated that quercetin protects GSVs by reducing the oxidative damage and inflammatory response and also suppresses the abnormal thickening of venous endothelium by inhibiting cell proliferation. It reminded that, to some extent, quercetin has the potential to release the great saphenous vein graft damage.
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INTRODUCTION: To evaluate the value of artificial intelligence (AI)-assisted software in the diagnosis of lung nodules using a combination of low-dose computed tomography (LDCT) and high-resolution computed tomography (HRCT). METHOD: A total of 113 patients with pulmonary nodules were screened using LDCT. For nodules with the largest diameters, an HRCT local-target scanning program (combined scanning scheme) and a conventional-dose CT scanning scheme were also performed. Lung nodules were subjectively assessed for image signs and compared by size and malignancy rate measured by AI-assisted software. The nodules were divided into improved visibility and identical visibility groups based on differences in the number of signs identified through the two schemes. RESULTS: The nodule volume and malignancy probability for subsolid nodules significantly differed between the improved and identical visibility groups. For the combined scanning protocol, we observed significant between-group differences in subsolid nodule malignancy rates. CONCLUSION: Under the operation and decision of AI, the combined scanning scheme may be beneficial for screening high-risk populations.
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Exosomes are nanosized vesicles secreted by most cells, which can deliver a variety of functional lipids, proteins, and RNAs into the target cells to participate in complex intercellular communications. Cells respond to certain physical, chemical, and biological stimuli by releasing exosomes. Exosomes are rich in small molecules of RNA, including miRNAs and mRNAs, which have been demonstrated to have certain functions in recipient cells. Recent studies on single-cell RNA sequences have revealed the transcription and the heterogeneity of macrophages in Ldlr-/-mice fed with a high-fat diet. Five macrophage populations were found in the atherosclerotic plaques. It is worth noting that these subset populations of macrophages seem to be endowed with different functions in lipid metabolism and catabolism. A total of 100 differentially expressed mRNAs were selected for these subset populations. Importantly, these macrophage populations were also present in human advanced atherosclerosis. To clarify the specific functions and the regulatory mechanism of these macrophage populations, we extracted exosome RNAs from the plasma of patients with chronic coronary artery disease (CAD) and performed RNA sequencing analysis. Compared with the healthy control, a total of 14 miRNAs were significantly expressed in these patients. A total of 5,248 potential mRNAs were predicted by the bioinformatics platform. Next, we determined the outcome of the intersection of these predicted mRNAs with 100 mRNAs expressed in the above-mentioned five macrophage populations. Based on the screening of miRNA-mRNA pairs, a co-expression network was drawn to find out the key RNAs. Three down-regulated miRNAs and five up-regulated mRNAs were selected for validation by real-time RT-PCR. The results showed that the expression of miR-4498 in plasma exosomes was lower than that in the healthy control, and the expressions of Ctss, Ccr2 and Trem2 mRNA in peripheral blood mononuclear cells isolated from CAD patients were higher. In order to clarify the regulatory mechanism, we established a co-culture system in vitro. Studies have shown that the uptake of exosomes from CAD patients can up-regulate the expression of Ctss, Trem2, and Ccr2 mRNA in THP-1 cells induced by lipopolysaccharide. Our findings revealed a unique relationship between the transcriptional signature and the phenotypic heterogeneity of macrophage in the atherosclerotic microenvironment.
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Estenose Coronária/genética , Exossomos/metabolismo , Macrófagos/fisiologia , Placa Aterosclerótica/genética , Idoso , Animais , Biodiversidade , Catepsinas/genética , Catepsinas/metabolismo , Técnicas de Cocultura , Biologia Computacional , Exossomos/genética , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Pessoa de Meia-Idade , Receptores CCR2/genética , Receptores CCR2/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Análise de Sequência de RNA , Células THP-1RESUMO
BACKGROUND: It is well known that androgen-deprivation therapy (ADT) can inevitably drive prostate cancer (PCa) cells into a castration-resistant state. According to the "Warburg effect", the metabolism of aggressive tumor cells increases significantly. The growth of cancer cells depends on glycolysis, which may be a potential target for cancer control. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) plays key roles in the proliferation and metastasis of PCa cells. However, there is very limited knowledge on the role of PFKFB4 in the conversion to castration resistance. The present study aimed to determine the changes in glucose consumption and PFKFB4 expression in LNCaP cells and androgen-independent LNCaP (LNCaP-AI) cells during the whole process of androgen-independent growth. Additionally, PFKFB4 expression in human PCa tissues was evaluated. METHODS: We established an androgen-independent LNCaP-AI cell line derived from LNCaP cells to mimic the traits of castration resistance in vitro. LNCaP-AI and LNCaP cells were cultured in the corresponding medium containing the same amount of glucose. At the end of experiments, the medium supernatant and blank medium were collected, and absorbance was measured. LNCaP-AI and LNCaP cells were harvested to detect PFKFB4 expression by Western blotting. Prostate tissue samples including PCa tissue, carcinoma-adjacent tissue and benign prostatic hyperplasia (BPH) tissue specimens were evaluated for PFKFB4 expression using immunohistochemistry. RESULTS: In 18 h supernatant samples, the glucose consumption and lactate secretion of LNCaP-AI cells were higher than those of LNCaP cells. The Western blot results indicated that PFKFB4 expression was increased in LNCaP-AI cells compared with LNCaP cells. Immunohistochemistry revealed that the expression of PFKFB4 in PCa tissue specimens was higher than that in BPH and adjacent tissue specimens. However, the differences in PCa tissue before and after ADT were not statistically significant. CONCLUSION: PFKFB4 may be associated with enhanced glycolysis during the androgen-independent growth of PCa cells in vitro. PFKFB4 may be a marker of PCa progression. Our results provide a rationale for further clinical investigation of PCa treatment focused on controlling PFKFB4 expression.
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Fosfofrutoquinase-2/biossíntese , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proliferação de Células , Humanos , Masculino , Células Tumorais CultivadasRESUMO
BACKGROUND: Signal regulatory protein alpha (SIRPa) is an essential signalling molecule that modulates inflammatory responses in macrophages. However, the regulation of SIRPs and its dynamic changes in macrophages under inflammatory stimulation in atherosclerosis remain uncertain. OBJECTIVE: The study aimed to identify the miRNAs that regulate SIRPa transcription and their roles in modulating phagocytosis, differentiation and cholesterol efflux in macrophages. METHODS: ApoE knockout mice were fed with a high-fat diet for 12 weeks. Intimal lesion areas and lipid accumulation were assessed by haematoxylin and eosin (HE) and oil red O staining. The expression of mRNAs/miRNAs was assessed by RNA-seq (RNA sequencing) and RT-qPCR (real-time quantitative polymerase chain reaction). The identification of miR-378a associated with SIRPa regulation in macrophages induced by ox-LDL was confirmed by RT-qPCR and Western blot. The phagocytosis and differentiation of macrophages were detected to figure out the role of miR-378a and SIRPa. RESULTS: SIRPa was proved to be a target of miR-378a. Reduced miR-378a can promote the expression of SIRPa. RNA-seq data showed that the levels of mRNA associated with macrophage phenotypes and SIRPa-CD47 axis were increasing significantly with a decreasing phagocytic phenotype in ApoE-/- mice vs wild-type (WT) mice (P < 0.01). The level of miR-378a was reduced in the aorta of ApoE-/- mice vs WT mice. The experiment in vitro showed that overexpression of miR-378a in macrophages decreased the level of Sirpa mRNA obviously vs control (P < 0.01). The phagocytic activity of miR-378a-transfected macrophages was promoted vs control (P < 0.05). miR-378a significantly depleted Sirpa levels in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages (P < 0.05), and depletion of miR-378a reversed Sirpa reduction obviously (P < 0.05). miR-378a promoted the secretion of TNF-a and IL-6 indirectly. CONCLUSION: It has been demonstrated that miR-378a regulates SIRPa-mediated phagocytosis and polarization of macrophages by a direct or indirect way. This research may provide a new path to promote reverse cholesterol transport of macrophages and hinder the progress of atherosclerosis.
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Aterosclerose/genética , Inflamação/genética , Macrófagos/fisiologia , MicroRNAs/genética , Animais , Aterosclerose/imunologia , Antígeno CD47/genética , Diferenciação Celular , Células Cultivadas , Colesterol/metabolismo , Dieta Hiperlipídica , Humanos , Inflamação/imunologia , Camundongos , Camundongos Knockout para ApoE , Fagocitose/genética , Receptores Imunológicos/genética , Transdução de SinaisRESUMO
Macrophages play a pivotal role in destabilizing atherosclerotic plaque. The diverse phenotypes and complex autophagy in macrophage are observed in atherosclerotic lesions. Tanshinone IIA (TNA) is known as the major component extracted from the root of Chinese herb Salvia miltiorrhiza, used for treatment of cardiovascular diseases. However, the therapeutic mechanism of TNA is not clear yet. In this study, we identified inflammation-related gene expression by microarray in atherosclerotic plaques in ApoE knockout mice fed with high fat diet and found miR-375 was one of the significantly high expressed microRNAs compared with wild type mice and TNA treated mice. Then we compared the levels of proteins related to the signal pathway of autophagy, and the phenotype of macrophages in atherosclerotic plaques ex vivo. We predicted KLF4 might be the key target of miR-375 that mediated the crosstalk between autophagy and polarization by TNA. Furthermore, we detected the expression of signal pathway in ox-LDL induced macrophages after treatment with TNA in vitro to verify this predict. The results suggest TNA could activate KLF4 and enhance autophagy as well as M2 polarization of macrophages by inhibiting miR-375 to Attenuate Atherosclerosis.
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Abietanos/uso terapêutico , Aterosclerose/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fatores de Transcrição Kruppel-Like/metabolismo , Macrófagos/fisiologia , MicroRNAs/genética , Animais , Apolipoproteínas E/genética , Autofagia , Diferenciação Celular , Células Cultivadas , Dieta Hiperlipídica , Modelos Animais de Doenças , Humanos , Fator 4 Semelhante a Kruppel , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor Cross-Talk , Salvia miltiorrhiza/imunologia , Transdução de SinaisRESUMO
This study investigated the effects of turbulence and oil dispersants on release of petroleum hydrocarbons in oil-sediment aggregates. A kinetic study showed that the static oil release process could be fitted to the first-order kinetics model. The oil concentration increased with increasing temperature and salinity, while remaining independent of pH. The dispersant desorption ability of petroleum hydrocarbons followed the sequence of: Tween 80 > Tween 85 > Span 80 > DOSS. In the presence of turbulence, the maximum release ratio was 40.28%. However, the combination of dispersants and turbulence had a smaller effect than turbulence alone. Furthermore, residual n-alkanes and PAHs in the sediments were analyzed. The results showed higher proportions of C15-C35 and 2-3 ring PAHs in residual oil. These results can help assess the fate and distribution of oil spills in marine environments.
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The clinical effects and safety of release and decompression techniques on nerve roots through percutaneous transforaminal endoscopic discectomy (PTED) while treating patients with central lumbar disc herniation (CLDH) were explored. Patient cases of lumbar and leg pain treated in Bethune International Peace Hospital from July 2013 to October 2015 were collected retrospectively. The patients in these cases received imaging examinations such as computed tomography and magnetic resonance imaging. Among these cases, 37 CLDH patients with no other complications were selected for this study. A total of 22 males and 15 females aged 28-54 years, with an average age of 36.8±1.5 years, were the subjects of the study. Their disease course was from 1 month to 3 years, with a median course time of 1.5 years. Visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) scoring and the MacNab method were used to evaluate treatment effects. After permission from patients or their family members, release and decompression techniques of nerve roots were performed through PTED. All patients had successful surgery. Their average surgery time was 41.3 (25.5-57.1) min. A physician followed-up each patient from 0 to 18 months after surgery, with the average follow-up period of 12.1 months. VAS scoring of lower limbs was 7.95±0.82 before surgery and 2.28±0.35, 3 months after surgery. VAS scoring of lower limbs was 2.06±0.58, 1 year after surgery and 2.12±0.23 at the last follow-up appointment. JOA scoring was 12.6±0.72 before surgery and 20.4±1.08, 3 months after surgery. JOA scoring was 21.1±0.82 1 year after surgery and 21.2±0.36 at the last follow-up. Differences are of statistical significance (P<0.05). There were no complications for any of the cases. One patient did not improve after surgery, so a laminectomy and bone grafting internal fixation were performed. Two patients relapsed after surgery and received laminectomy and bone grafting internal fixation. The total percentage of excellent and good rates was 83.5%. In conclusion, release and decompression techniques on nerve roots using PTED while treating CLDH resulted in a safe, effective and less traumatic outcome with fewer complications and quicker pain relief than alternative treatments. Due to the results of this study, the use of these techniques in treating CLDH should be more widely considered.
RESUMO
STUDY DESIGN: The pattern of neurological recovery in the overall modified Japanese Orthopedic Association scores, upper limb function score, and lower limb function score after surgical decompression for patients suffering from multilevel cervical spondylotic myelopathy (CSM) were analyzed in this independent retrospective study. OBJECTIVE: The primary objective of this retrospective study was to compare the upper and lower limb function changes after anterior decompression with fusion versus posterior decompression with laminoplasty for patients suffering from multilevel CSM. An additional objective was to describe the neural recovery speed. SUMMARY OF BACKGROUND DATA: Few comparative studies have been conducted to evaluate the outcome of anterior versus posterior surgery in multilevel CSM. However, these assessments tend to be of a more global perspective, looking at a composite score for upper limb, lower limb, and bladder function. No reports have separately analyzed the upper and lower limb function changes after anterior and posterior decompression for multilevel CSM. MATERIALS AND METHODS: A total of 132 patients were classified into anterior and posterior decompression groups based on the different surgical approach they underwent. The pattern of neurological recovery in the overall modified Japanese Orthopedic Association scores, upper limb function score, and lower limb function score after surgical decompression were documented and analyzed. RESULTS: There was no significant difference in the overall neurological recovery between anterior and posterior decompression groups. But in terms of the upper or lower limb function changes after operation, it appeared that the upper limbs recovered better with anterior decompression. The surgical approach did not significantly alter lower extremity recovery potential. In addition, most of the neurological recovery occurred in the first 9 months after surgical decompression. CONCLUSIONS: We recommend a individualized approach when it is difficult to determine an anterior or posterior surgery for multilevel CSM. Rehabilitation training should be carried out as early as possible.
Assuntos
Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/métodos , Laminoplastia , Recuperação de Função Fisiológica , Fusão Vertebral/métodos , Espondilose/cirurgia , Descompressão Cirúrgica/efeitos adversos , Feminino , Humanos , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Fusão Vertebral/efeitos adversos , Extremidade Superior/fisiopatologiaRESUMO
OBJECTIVE: To explore the relationship of postoperative cognitive dysfunction (POCD) in one-lung ventilation (OLV) patients and regional cerebral oxygen saturation (rSO2). METHODS: Twenty-nine male and twenty-one female cases of OLV received thoracic surgery, with American Standards Association (ASA) physical status being at Grades I-III. Neuropsychological tests were performed on the day before operation and 7 d after operation, and there was an intraoperative continuous monitoring of rSO2. The values of rSO2 before anesthesia induction (t1), at the beginning of OLV (t2), and at the time of OLV 30 min (t3), OLV 60 min (t4), the end of OLV (t5), and the end of surgery (t6) were recorded. The intraoperative average of rSO2 , the intraoperative minimum value of rSO2 (rSO(2, min)), and the reduced maximum percentage of rSO2 (rSO(2, %max)) when compared with the baseline value were calculated. The volume of blood loss, urine output, and the amount of fluid infusion was recorded. RESULTS: A total of 14 patients (28%) in the 50 cases suffered from POCD. The values of mini-mental state examination (MMSE), the digit span and the digit symbol on the 7th day after the operation for POCD in OLV patients were found to be significantly lower than those before the operation (P<0.05). The values of MMSE and vocabulary fluency scores were significantly lower than those in the non-POCD group (P<0.05). The values of rSO2 in the POCD group of OLV patients at t2 and t3 and the values of rSO2 in the non-POCD group at t2 were found to be significantly higher than those at t1 (P<0.05). The values of rSO(2, %max) in the POCD group were significantly higher than those in the non-POCD group (P<0.05). When the value of rSO(2, %max) is more than 10.1%, it may act as an early warning index for cognitive function changes. CONCLUSIONS: POCD after OLV may be associated with a decline in rSO2.