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Objective: To characterize the gas production phenomenon in the animal model of left ventricular assist device (LVAD), and study its mechanism. Methods: An in vitro bubble precipitation experiment was conducted, and the blood samples of Parma spp. animals were divided into ordinary group and oxygen-enriched group according to whether they were oxygenated or not at the time of blood collection, and a static control group was set up respectively. Blood gases were drawn and analyzed before and after the experiment. Activate the pump, and the number of air bubbles in the loop was measured by ultrasound at different rotational speeds; CFD was applied to simulate the flow field in the blood pump, and pressure, fluid velocity vector and shear force diagrams were plotted, and a thrombus model was constructed and the flow field was simulated and plotted as a cloud diagram. Results: There was a statistical difference in the number of bubbles in the inflow and outflow tubes of the blood pump (P values of 0.04 and 0.023, respectively), and the number of bubbles in the outflow tubes of both groups was significantly higher than the number of bubbles in the inflow tubes. The number of bubbles in the tubes of both the oxygen-enriched and normal groups was significantly higher than that in the inflow group. In both the normal and oxygen-enriched groups, more gas was produced at higher speeds than at lower speeds. Blood gas analysis showed that the reduced gas composition in the blood was mainly oxygen. Flow field simulation results: the high rotation speed group had lower central pressure and greater scalar shear. The thrombus simulation group was more prone to turbulence, sudden pressure changes, and greater shear than the normal group. Conclusion: Blood gas production is associated with higher partial pressures of blood oxygen, higher rotation speed, and intrapump thrombosis, and the mechanism of pump gas production is degassing of dissolved gases rather than cavitation of water, and the gas released is most likely to have oxygen. The degassing phenomenon is an warning factor for pump thrombosis.
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BACKGROUND AND AIMS: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR. METHODS: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. RESULTS: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. CONCLUSIONS: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).
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Fígado , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Fígado/patologia , Fígado/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Crônica Induzida por Substâncias e Drogas/etiologia , Resultado do Tratamento , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Recidiva , Idoso , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Esquema de MedicaçãoRESUMO
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and emerging evidence suggests that the gut microbiota may play a role in its development and progression. In this study, the association between B. thetaiotaomicron, a gut microbiota species, and HCC recurrence, as well as patient clinical outcomes, was investigated. It was observed that B. thetaiotaomicron-derived acetic acid has the potential to modulate the polarization of pro-pro-inflammatory macrophagess, which promotes the function of cytotoxic CD8+ T cells. The increased biosynthesis of fatty acids was implicated in the modulation of pro-inflammatory macrophages polarization by B. thetaiotaomicron-derived acetic acid. Furthermore, B. thetaiotaomicron-derived acetic acid was found to facilitate the transcription of ACC1, a key enzyme involved in fatty acid biosynthesis, through histone acetylation modification in the ACC1 promoter region. Curcumin, an acetylation modification inhibitor, significantly blocked the inhibitory effects of B. thetaiotaomicron and acetic acid on HCC tumor growth. These findings highlight the potential role of gut microbiota-derived acetic acid in HCC recurrence and patient clinical outcomes, and suggest a complex interplay between gut microbiota, immune modulation, fatty acid metabolism, and epigenetic regulation in the context of HCC development. Further research in this area may provide insights into novel strategies for HCC prevention and treatment by targeting the gut microbiota and its metabolites.
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Carcinoma Hepatocelular , Microbioma Gastrointestinal , Neoplasias Hepáticas , Humanos , Ácido Acético , Epigênese Genética , Ácidos Graxos , Microambiente TumoralRESUMO
BACKGROUND: The role of carbohydrate antigen 19-9 (CA 19-9) in response assessment among patients with intrahepatic cholangiocarcinoma (iCCA) remains unknown. The authors studied the association of the CA 19-9 response (defined as a reduction >50% from baseline) with the radiologic response and the outcome in patients with unresectable iCCA. METHODS: A prospective cohort of 422 patients who were initially diagnosed with unresectable iCCA, had baseline CA 19-9 levels ≥100 U/mL, and received treatment with systemic therapies at the authors' institution between January 2017 and December 2021 were enrolled in this study. The radiologic response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A landmark assessment of the CA 19-9 response and the radiologic response was performed. The associations between CA 19-9 response and imaging response, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Two hundred sixty-seven patients (63.3%) had a CA 19-9 response. A CA 19-9 response was observed in 123 of 132 (93.2%) radiologic responders and in 144 of 290 (49.7%) radiologic nonresponders (p < .001). CA 19-9 responders outperformed nonresponders in median PFS (10.6 vs. 3.6 months; hazard ratio [HR], 4.8 months; 95% confidence interval [CI], 3.8-6.0 months; p < .001) and OS (21.4 vs. 6.3 months; HR, 5.3 months; 95% CI, 4.2-6.7 months; p < .001). The common independent predictors of both OS and PFS included metastasis, CA 19-9 nonresponder status, and radiologic nonresponder status in multivariable analysis. CONCLUSIONS: CA 19-9 response is a valuable addition to assess tumor response and is associated with improved outcomes in patients with iCCA. Achieving a CA 19-9 response should be one of the therapeutic objectives of patients with iCCA after systemic therapies. PLAIN LANGUAGE SUMMARY: A decline in carbohydrate antigen 19-9 levels from elevated baseline levels should be one of the therapeutic aims of patients with intrahepatic cholangiocarcinoma who are managed with systemic therapies.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Estudos Prospectivos , Colangiocarcinoma/tratamento farmacológico , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Carboidratos/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: The role of chemoradiotherapy in unresectable locally advanced pancreatic cancer is still unclear. METHODS: Data from patients with unresectable locally advanced pancreatic cancer were extracted from the Surveillance, Epidemiology, and End Results Program database. Univariate and multivariate Cox regression analyses were conducted to identify the independent prognostic factors of survival. Propensity score matching was carried out to minimize the interference of confounding factors. Subgroup analysis was performed to screen the characteristics of patients who would benefit from chemoradiotherapy. RESULTS: A total of 5002 patients with unresectable locally advanced pancreatic cancer were included. Among them, 2423 (48.4%) received chemotherapy, and 2579 (51.6%) received chemoradiotherapy. The median overall survival of all patients was 11 months. Multivariate Cox analysis showed that age (p < 0.001), marital status (p < 0.001), tumor size (p = 0.001), N stage (p = 0.015) and radiotherapy (p < 0.001) were independent prognostic factors of survival. Both before (HR, 0.817; 95% CI, 0.769-0.868; p < 0.001) and after (HR, 0.904; 95% CI, 0.876-0.933; p < 0.001) propensity score matching, chemoradiotherapy significantly improved the median overall survival of patients from 10 to 12 months. Subgroup analysis showed that chemoradiotherapy was significantly associated with improved survival regardless of sex, primary site or N stage. In addition, the following subgroups all significantly benefited from chemoradiotherapy: age ≥ 50 years, not divorced, grade 2-4, tumor size > 2 cm, adenocarcinoma, mucinous adenocarcinoma and white race. CONCLUSIONS: Chemoradiotherapy is highly recommended for patients with unresectable locally advanced pancreatic cancer.
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Neoplasias Pancreáticas , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Pancreáticas/patologia , Quimiorradioterapia , Estudos de Coortes , Neoplasias PancreáticasRESUMO
Background: This research sought to elucidate the effects of peroxiredoxin 6 (PRDX6) on the biological processes in diabetic nephropathy (DN) and to identify the underlying regulatory mechanism related to toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling. Methods: To induce an in vitro DN cellular model, human kidney 2 (HK-2) cells were treated with high glucose (HG). The mitochondrial membrane potential, adenosine triphosphate level, reactive oxygen species generation, and oxidative stress of the cells were then evaluated. After the PRDX6 level had been determined, the effects of its overexpression on the mitochondrial membrane potential, adenosine triphosphate level, reactive oxygen species generation, and oxidative stress of the cells were assessed. Next, cytochrome c expression, cell viability, cell apoptosis, the inflammatory level, and the TLR4/NF-κB signaling-related factors were assessed. After the addition of the TLR4 activator CRX-527 or the NF-κB activator phorbol 12-myristate 13-acetate (PMA), cell viability, cell apoptosis and the inflammatory level were evaluated again. Results: The results revealed that HG exposure triggered mitochondrial dysfunction and oxidative stress and decreased PRDX6 expression in the HK-2 cells. PRDX6 elevation exacerbated cell viability while alleviating mitochondrial membrane potential loss, oxidative stress, apoptosis, and inflammation in the HG-treated HK-2 cells. Further, PRDX6 inhibited HG-induced TLR4/NF-κB activation. The administration of CRX-527 or PMA reversed the effects of PRDX6 on the cell viability, apoptosis, and inflammation of the HG-exposed HK-2 cells. Conclusions: To conclude, PRDX6 appears to protect HG-exposed HK-2 cells against inflammation and apoptosis by inhibiting TLR4/NF-κB signaling.
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OBJECTIVE: To analyze the correlation between the mRNA levels of breast cancer resistance protein (BCRP) and lung-specific X protein (LUNX) genes with pathological types and stages of patients with non-small cell lung cancer (NSCLC) and their significance for prognosis. METHODS: Eighty nine patients with NSCLC admitted to Huaihe Hospital of Henan University between June 2015 and June 2018 were recruited, with 55 patients with benign lung lesions admitted during the same period of time selected as the control group. The mRNA levels of BCRP and LUNX genes were detected in the peripheral blood samples from the two groups, and their correlation with the clinicopathological characteristics and prognosis of the patients was analyzed. RESULTS: The expression rates of BCRP and LUNX mRNA in the NSCLC group were significantly higher compared with the control group (P < 0.05). The level of BCRP mRNA of the NSCLC patients has correlated with the degree of differentiation and TNM staging (P < 0.05), but not with gender, age, smoking, pathological types and lymph node metastasis (P > 0.05). The level of LUNX mRNA of them has correlated with the degree of differentiation, TNM staging and lymph node metastasis (P < 0.05), but not with gender, age, smoking, and pathological types (P > 0.05). Compared with those with no expression, the overall survival rate of patients with BCRP and LUNX expression was significantly lower (P < 0.05). The degree of differentiation, TNM staging, lymph node metastasis, and expression of the BCRP and LUNX mRNA may all affect the prognosis of the patients. CONCLUSION: The levels of BCRP and LUNX mRNA in the peripheral blood of patients with NSCLC are significantly increased. The expression of BCRP mRNA is correlated with the degree of differentiation and TNM staging, whilst the expression of LUNX mRNA is correlated with the differentiation degree, TNM staging and lymph node metastasis. Both may be used as independent predictors for the prognosis of patients with NSCLC.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Carcinoma Pulmonar de Células não Pequenas , Glicoproteínas , Neoplasias Pulmonares , Fosfoproteínas , Humanos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Glicoproteínas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Linfática , Proteínas de Neoplasias/genética , Fosfoproteínas/genética , Prognóstico , RNA Mensageiro/genéticaRESUMO
PURPOSE: As a non-invasive treatment, stereotactic body radiation therapy (SBRT) has been an emerging and effective option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). The Cyber Knife has an SBRT system, which can realize real-time tracking of tumors during treatment. It can protect the surrounding normal liver tissue while the tumor gets the therapeutic dose. The purpose of this study was to evaluate the factors affecting the local control rate for patients after SBRT treatment, and to predict the factors affecting survival rates, then to report the 3-year actual survival rates after treatment and identify the influencing factors of 3-year survival rate. MATERIALS AND METHODS: We conducted a long-term follow-up of 43 patients with unresectable intrahepatic cholangiocarcinoma who underwent Cyber Knife in our hospital from January 2016 to December 2018. Regular medical check-ups were performed every 2-3 months after SBRT to evaluated the effect of treatment. RESULTS: The median follow-up time was 15 months (4-78 months), and the median progression-free survival (PFS) was 6 months (95% CI, 2.788-9.212) and the median overall survival (OS) was 12 months (95% CI, 3.434-20.566), respectively. Based on modified Response Evaluation and Criteria in Solid Tumor (mRECIST), response rate (RR) and disease control rate (DCR) of SBRT in unresectable ICC were 55.2% and 86%. The 1-, 2- and 3-years OS rate were 51.2%, 32.6% and 23.3%. Multivariate analysis based on competing risk survival analysis identified that patients with multiple nodules, large diameter, high level of CA199 and CEA, poor ECOG performance status had worse overall survival (p < 0.05). Patients who survived ≥3 years had significantly lower levels of CEA, CA199, smaller tumor diameters and lower number of lesions (p < 0.05). CONCLUSION: The SBRT might be a candidate option for patients who unable to perform surgery. The rate of 3-year survival after SBRT for unresectable ICC can be expected with 23.3%.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Resultado do Tratamento , Colangiocarcinoma/radioterapia , Colangiocarcinoma/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/efeitos da radiação , Neoplasias dos Ductos Biliares/patologia , Estudos RetrospectivosRESUMO
Objective: To study the correlation between serum sclerostin (SO) and arterial stiffness in peritoneal dialysis (PD) patients. Methods: The study included 50 Parkinson's disease (PD) patients on continuous ambulatory peritoneal dialysis (CAPD) for more than 6 months at the nephrology department of our hospital. Without regard for age, the eligible patients were assigned to a low PWV group and a high PWV group with brachial-ankle pulse wave velocity (Ba PWV) of 1400 cm/s as the cutoff value. Patient characteristics such as age, gender, height, weight, BMI, smoking history, dialysis age, systolic blood pressure (SBP), diastolic blood pressure (DBP), urea clearance index (Kt/V), residual renal function (RRF), and diabetes mellitus (DM) were analyzed. Biochemical indices for analysis include hemoglobin (Hb), albumin (ALB), total cholesterol (TC), urea nitrogen (BUN), creatinine (CREA), triglyceride (TG), uric acid (UA), parathyroid hormone (PTH), blood phosphorus(P), fasting blood glucose (GLU), corrective calcium (Ca), calcium-phosphorus product, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), SO, and arterial stiffness. Results: There were 9 males and 16 females in the low PWV group and 12 males and 13 females in the high PWV group. Statistical significance was absent in patient characteristics despite more males in the high PWV group (P=0.055). The low PWV group had significantly lower mean age, SBP, SO, and PWV level, fewer diabetic patients, and higher CREA than the control group. Analysis of PWV-related factors showed that PWV was positively correlated with age, P, Ca, GLU, SBP, PTH, and SO while negatively correlated with CREA. Multiple stepwise regression analysis showed that age, SO, and SBP demonstrated great potential to predict PWV (P < 0.05). Conclusion: The degree of vascular sclerosis is highly correlated with SO level in Parkinson's disease patients, which might provide a theoretical basis for the evaluation of cardiovascular illness in Parkinson's disease patients. High serum sclerostin level is a risk factor for deteriorated arterial stiffness. Given the limited sample size, the relevant results require further validation by expanding the sample size.
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Grassland degradation has become a serious problem in some areas, making it necessary to quantitatively evaluate this process and its related factors. The study area was the arid windy sandy area in eastern Ningxia. The purpose of this study was to explore how soil properties and quality change during the process of grassland degradation in arid windy sandy areas. We looked at undegraded, lightly degraded, moderately degraded, and severely degraded desert steppe to study the physical, chemical, and biological changes at 0-5 cm, 5-15 cm, and 15-30 cm soil depths at different degradation degrees. We also analyzed the correlations across soil factors, established the minimum data set, and used the soil quality index (SQI) to evaluate the soil quality of grassland at different degradation degrees. The results showed that with grassland degradation, the soil bulk density increased; the soil clay, moisture, organic matter, total nitrogen, and available potassium content decreased; and the number of soil bacteria, actinomycetes, and fungi, as well as the activity of urease, polyphenol oxidase, protease, phosphatase, and sucrase, decreased. As soil depth increased, soil bulk density increased; the soil moisture, organic matter, available potassium, and available phosphorus content decreased; and soil microorganisms accumulated in the upper soil of undegraded, lightly, and moderately degraded grassland. There was also a positive correlation among the soil clay content, moisture content, organic matter content, total nitrogen content, available potassium content, microorganism quantity, and enzyme activity, while soil bulk density was negatively correlated with the above factors. The minimum data set for the soil quality evaluation of the degraded desert steppe was comprised of soil organic matter content, soil total nitrogen content, soil available phosphorus content, and phosphatase activity. Based on the minimum data set, we calculated the SQI of the grassland at different degradation degrees and found that the ranking based on overall soil quality was undegraded >lightly degraded >moderately degraded >severely degraded grassland. The results showed that the degradation of desert steppe in arid windy sandy areas had relatively consistent effects on the physical, chemical, and biological traits of the soil. The minimum data set can be used to replace the total data set when evaluating the soil quality of the desert steppe at different degrees of degradation.
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Areia , Solo , Solo/química , Argila , Nitrogênio/análise , FósforoRESUMO
[This corrects the article DOI: 10.1155/2021/8851763.].
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Berbamine (BBM), one of the bioactive ingredients extracted from Berberis plants, has attracted intensive attention because of its significant antitumor activity against various malignancies. However, the exact role and potential molecular mechanism of berbamine in bladder cancer (BCa) remain unclear. In the present study, our results showed that berbamine inhibited cell viability, colony formation, and proliferation. Additionally, berbamine induced cell cycle arrest at S phase by a synergistic mechanism involving stimulation of P21 and P27 protein expression as well as downregulation of CyclinD, CyclinA2, and CDK2 protein expression. In addition to suppressing epithelial-mesenchymal transition (EMT), berbamine rearranged the cytoskeleton to inhibit cell metastasis. Mechanistically, the expression of P65, P-P65, and P-IκBα was decreased upon berbamine treatment, yet P65 overexpression abrogated the effects of berbamine on the proliferative and metastatic potential of BCa cells, which indicated that berbamine attenuated the malignant biological activities of BCa cells by inhibiting the NF-κB pathway. More importantly, berbamine increased the intracellular reactive oxygen species (ROS) level through the downregulation of antioxidative genes such as Nrf2, HO-1, SOD2, and GPX-1. Following ROS accumulation, the intrinsic apoptotic pathway was triggered by an increase in the ratio of Bax/Bcl-2. Furthermore, berbamine-mediated ROS accumulation negatively regulated the NF-κB pathway to a certain degree. Consistent with our in vitro results, berbamine successfully inhibited tumor growth and blocked the NF-κB pathway in our xenograft model. To summarize, our data demonstrated that berbamine exerts antitumor effects via the ROS/NF-κB signaling axis in bladder cancer, which provides a basis for further comprehensive study and presents a potential candidate for clinical treatment strategies against bladder cancer.
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Benzilisoquinolinas/farmacocinética , NF-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Bexiga Urinária/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Nus , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: The association between LINC01305, a newly discovered long non-coding RNA (lncRNA), and cervical cancer (CC) has been poorly analyzed. In the present study, we revealed high expression of LINC01305 in CC by the cancer genome atlas (TCGA) and Gene Expression Omnibus (GEO), and dissected the related mechanisms. METHODS: LINC01305, microRNA (miR) -129-5p and SRY-related high-mobility group box 4 (Sox4) mRNA levels were quantitated by quantitative reverse transcription-PCRy qRT-PCR). CC tissues and cell lines and corresponding controls were enrolled for the quantification of LINC01305 expression in CC. Effects of LINC01305 and miR-129-5p on cell proliferation, metastasis, and apoptosis were evaluated by MTT, colony formation, wound healing, Transwell and flow cytometry assays. Sox4 protein levels were tested by Western blot (WB). Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down and dual-luciferase reporter (DLR) assay were performed to determine molecular mechanisms of LINC01305 in CC. Xenograft models of CC were constructed to evaluate the role of LINC01305 in vivo. RESULTS: The expression of LINC01305 was evidently elevated in CC tissues and cell lines than that in controls and associated with clinicopathological features. Downregulating LINC01305 suppressed malignant phenotypes (proliferation, migration, invasion) of Hela and SiHa cells. In addition, silencing miR-129-5p by its inhibitor eliminated the inhibition of growth and metastasis induced by LINC01305 siRNA. Sox4 might serve as a direct target for miR-129-5p and was negatively regulated by miR-129-5p and LINC01305. CONCLUSION: LINC01305 acts as a competitive endogenous RNA (ceRNA) and regulates Sox4 via sponging miR-129-5p, contributing to the diagnosis and treatment of CC.
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Genomic DNA is folded into a higher-order structure that regulates transcription and maintains genomic stability. Although progress has been made on understanding biochemical characteristics of epigenetic modifications in cancer, the in-situ higher-order folding of chromatin structure during malignant transformation remains largely unknown. Here, using optimized stochastic optical reconstruction microscopy (STORM) for pathological tissue (PathSTORM), we uncover a gradual decompaction and fragmentation of higher-order chromatin folding throughout all stages of carcinogenesis in multiple tumor types, and prior to tumor formation. Our integrated imaging, genomic, and transcriptomic analyses reveal functional consequences in enhanced transcription activities and impaired genomic stability. We also demonstrate the potential of imaging higher-order chromatin disruption to detect high-risk precursors that cannot be distinguished by conventional pathology. Taken together, our findings reveal gradual decompaction and fragmentation of higher-order chromatin structure as an enabling characteristic in early carcinogenesis to facilitate malignant transformation, which may improve cancer diagnosis, risk stratification, and prevention.
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Carcinogênese/patologia , Cromatina/patologia , Processamento de Imagem Assistida por Computador , Microscopia de Fluorescência/métodos , Neoplasias/diagnóstico por imagem , Animais , Biofísica , Epigênese Genética , Genoma , Heterocromatina , Humanos , Masculino , Camundongos , Neoplasias/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , TranscriptomaRESUMO
In recent years, studies demonstrate that ACTB has been found to be associated with various tumors. Although ACTB is dysregulated in numerous cancer types, limited data are available on the potential function and mechanism of ACTB in hepatocellular carcinoma (HCC). This study evaluated the expression and biological roles of mutant ACTB mRNA 3'-UTR in HCC. Transcriptome sequence and qRT-PCR analysis determined that mutant ACTB mRNA '-UTR was high expression in tumor tissues. Luciferase reporter assay showed that the ACTB mRNA 3'-UTR mutations made it easier to interact with miR-1 and miR-29a. Moreover, mutant ACTB mRNA '-UTR regulated miR-1 and miR-29a degradation via AGO2. Furthermore, mutant ACTB mRNA 3'-UTR promoted hepatocellular carcinoma cells migration and invasion in vitro and in vivo by up-regulating miR-1 target gene MET and miR-29a target gene MCL1. In a word, our study demonstrates that 3'-UTR of ACTB plays a key role in the development of hepatocellular carcinoma (HCC) and highlights the molecular mechanisms underlying such a complex process.
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Regiões 3' não Traduzidas/genética , Actinas/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Mutação/genética , Actinas/metabolismo , Animais , Proteínas Argonautas/metabolismo , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Essenciais , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Modelos Biológicos , Estabilidade de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology to detect pancreatic cancer is limited, with a high false negative rate mainly due to the relatively fewer number of completely cancerous cells. To improve the accuracy of EUS-FNA cytological diagnosis, we evaluated a novel optical system-spatial-domain low-coherence quantitative phase microscopy (SL-QPM)-to analyze nanoscale nuclear architecture on original cytology samples, especially those diagnosed as indeterminate for malignancy, with the goal of maintaining high specificity and reducing false positive rate. We performed SL-QPM on original cytology samples obtained by EUS-FNA from 40 patients with suspicious pancreatic solid lesions (27 adenocarcinomas, 5 neuroendocrine tumor, 8 chronic pancreatitis), including 13 cases that were cytologically indeterminate. Each diagnosis had been confirmed by follow-up surgical pathology. The SL-QPM-derived nanoscale nuclear architectural parameters distinguished pancreatic cancer from cytologically indeterminate cells. A logistic regression model using nuclear entropy and SD increased the sensitivity of cytology in identifying pancreatic cancer from 72% to 94% while maintaining 100% specificity. The SL-QPM-derived nanoscale nuclear architecture properties show great promise in improving the cytological diagnosis of EUS-FNA for pancreatic cancer and could be used when traditional cytopathology does not get an accurate diagnosis, and can be easily translated into a traditional clinical device.
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Microscopia de Contraste de Fase/métodos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Biópsia por Agulha Fina , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/patologia , Diagnóstico Diferencial , Feminino , Análise de Fourier , Humanos , Masculino , Pessoa de Meia-Idade , Nanotecnologia , Neoplasias Pancreáticas/diagnóstico , Pancreatite/diagnóstico por imagem , Pancreatite/patologia , Sensibilidade e Especificidade , Ultrassonografia de IntervençãoRESUMO
Background: Fibroblast growth factor 9 (FGF9) is reported to be associated with the pathogenesis of cancers. However, its clinic significance in prostate cancer (PCa) had not yet to be elucidated. The aim of this study was to investigate the diagnostic value of FGF9 in PCa. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were used to detect the expression of serum FGF9 at mRNA and protein level in 90 PCa patients, 48 prostatic benign diseases (PBD) patients and 30 normal individuals. The association between FGF9 and clinicopathological features was determined by Chi-square test. Receiver-operator characteristic (ROC) was established to evaluate the diagnostic performance of FGF9 and PSA. Results: Serum FGF9 expression was significantly elevated in PCa patients (p < .001) and was obviously decreased after surgery (p < .001). FGF9 expression was also associated with lymph node metastasis (p = .010). The diagnostic value of FGF9 was higher than the conventional tumor marker PSA with a AUC of 0.846 combined with a sensitivity of 83.3% and a specificity of 81.1%. Conclusions: Serum FGF9 may be employed as a potential diagnostic biomarker of PCa.
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Biomarcadores Tumorais/sangue , Fator 9 de Crescimento de Fibroblastos/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais/genética , Fator 9 de Crescimento de Fibroblastos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias da Próstata/genética , Curva ROCRESUMO
This study was designated to verify if the lncRNA H19/miR-193a-3p axis would play a regulatory role in the radio-/chemo-resistances of HCC cells through targeting PSEN1. Within the study, five human HCC cell lines were prepared, including Bel-7402, HepG2, Hep3b, QGY-7703, and SMMC-7721. Moreover, docetaxel (DT), paclitaxel (Pt), vinorelbine (Vb), and 5-fluorouracil (5-Fu) were managed as the chemo-therapeutics, and single-dose X-rays were performed as radio-therapies. Besides, lncRNA H19 and miR-193a-3p were detected by qRT-PCR and Western blot were implemented to quantify the expressional levels of PSEN1, Ku80, γ-H2AX, and RAD51. Luciferase reporter gene assay was advanced to verify the targeted relationship between lncRNA H19 and miR-193a-3p. As a consequence, QGY-7703 and Bel-7402 were, respectively, the most radiation-sensitive and radiation-proof cell lines, and Bel-7402 was associated with the highest resistances to DT, Pt, Vb, and 5-FU. The restrained lncRNA H19 and over-expressed miR-193a-3p expressions tended to significantly elevate the survival rate and proliferation of Bel-7402 cells, when they were exposed to radiation and subject to chemo-therapies. The lncRNA H19 was also found to directly target miR-193a-3p in inducing the HCC development. PSEN1 appeared to be subject to the modification of lncRNA H19 and miR-193a-3p in its acting on the survival rates and proliferative abilities of HCC cells. The lncRNA H19/miR-193a-3p/PSEN1 axis could be regarded as the treatment targets for HCC, so as to further improve the treatment efficacy of chemo- and radio-therapies for HCC.
Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Presenilina-1/genética , RNA Longo não Codificante/genética , Raios X , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Docetaxel/farmacologia , Fluoruracila , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatócitos/efeitos da radiação , Histonas/genética , Histonas/metabolismo , Humanos , Autoantígeno Ku/genética , Autoantígeno Ku/metabolismo , MicroRNAs/metabolismo , Paclitaxel/farmacologia , Presenilina-1/metabolismo , RNA Longo não Codificante/metabolismo , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , Tolerância a Radiação/genética , Transdução de Sinais , Vinorelbina/farmacologiaRESUMO
We intended to investigate the functional role and clinical relevance of microRNA-125b in human gallbladder cancer. Quantitative real-time polymerase chain reaction was used to examine microRNA-125b expression in gallbladder cancer cell lines, and 79 pairs of gallbladder cancer and normal gallbladder clinical tissues. Clinical correlations between tumorous microRNA-125b expression and gallbladder cancer patients' clinicopathological variances or overall survivals were statistically analyzed. In gallbladder cancer cell lines, TYGBK-8 and G-415 cells, microRNA-125b was upregulated to examine its regulatory effect on gallbladder cancer proliferation and migration in vitro. MicroRNA-125b was significantly downregulated in gallbladder cancer cell lines and human gallbladder cancer tumors. MicroRNA-125b in gallbladder cancer was significantly correlated with patients' clinical stage, tumor differentiation, lymph metastasis, and tumor invasion. Low tumorous microRNA-125b expression was also found to be associated with poor overall survivals among gallbladder cancer patients. In vitro studies demonstrated that microRNA-125b upregulation significantly suppressed proliferation and migration in TYGBK-8 and G-415 cells. Tumorous microRNA-125b is an independent prognostic biomarker for patients with gallbladder cancer and possibly acts as a tumor suppressor in gallbladder cancer.