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AIM: To explore the usage of choroidal thickness measured by swept-source optical coherence tomography (SS-OCT) to detect myopic macular degeneration (MMD) in high myopic participants. METHODS: Participants with bilateral high myopia (≤-6 diopters) were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study. SS-OCT was performed to determine the choroidal thickness, and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia (META-PM) Classiï¬cation. Presence of MMD was defined as META-PM category 2 or above. RESULTS: A total of 568 right eyes were included for analysis. Eyes with MMD (n=106, 18.7%) were found to have older age, longer axial lengths (AL), higher myopic spherical equivalents (SE), and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study (ETDRS) grid sector (P<0.001). The area under the receiver operating characteristic (ROC) curves (AUC) for subfoveal choroidal thickness (0.907) was greater than that of the model, including age, AL, and SE at 0.6249, 0.8208, and 0.8205, respectively. The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD (AUC of 0.928 and 0.923, respectively). An outer nasal sector choroidal thickness of less than 74 µm demonstrated the highest odds of predicting MMD (OR=33.8). CONCLUSION: Choroidal thickness detects the presence of MMD with high agreement, particularly of the inner and outer nasal sectors of the posterior pole, which appears to be a biometric parameter more precise than age, AL, or SE.
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Introduction: The ITGB6 gene encoding a protein that can regulate the integrin αvß6 heterodimer protein expression in different status was shown to play an important role in multiple human cancers, such as brain cancer, colon cancer and oral cancer, and is related to clinical progression. This study aims to explore the function and the mechanism of the ITGB6 gene or protein in pancreatic cancer. Material and methods: We examined the expression of ITGB6 in pancreatic cancer using immunohistochemistry and analyzed the relationship between the expression of ITGB6 and the clinicopathologic features in pancreatic cancer patients. In addition, a bioinformatic method was used to analyze the ITGB6 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the correlation between high KIF23 expression and prognosis in pancreatic cancer patients. Moreover, colony formation assay, MTT assay, cell scratch, cell invasion and western blot assays in vitro and a xenograft mouse model in vivo were performed to analyze the effect of KIF23 on proliferation and invasion of pancreatic cancer cells. Results: Increased expression of ITGB6 was significantly correlated with poor clinical outcome in both our clinical data and TCGA data of pancreatic cancer. Furthermore, functional assays revealed that ITGB6 knockdown in vivo and in vitro might inhibit cancer cell proliferation and the ability of invasion or migration. Conclusions: Our data suggest that ITGB6 is associated with pancreatic cancer malignant progression. Hence, ITGB6 may serve as a potential target of pancreatic cancer for future research, and further study is needed.
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BACKGROUND: The effects of postoperative adjuvant therapy for high-risk recurrent hepatocellular carcinoma (HCC) in immunotherapy are still under investigation. This study evaluated the preventive effects and safety of postoperative adjuvant therapy, including atezolizumab, and bevacizumab, against the early recurrence of HCC with high-risk factors. METHODS: The complete data of HCC patients who underwent radical hepatectomy with or without postoperative adjuvant therapy after two-year follow-up were analyzed retrospectively. The patients were divided into high-risk or low-risk groups based on HCC pathological characteristics. High-risk recurrence patients were divided into postoperative adjuvant treatment and control groups. Due to the difference in approaches in postoperative adjuvant therapies, they were divided into transarterial chemoembolization (TACE), atezolizumab, and bevacizumab (T + A), and combination (TACE+T + A) groups. The two-year recurrence-free survival rate (RFS), overall survival rate (OS), and associated factors were analyzed. RESULTS: The RFS in the high-risk group was significantly lower than that in the low-risk group (P = 0.0029), and the two-year RFS in the postoperative adjuvant treatment group was significantly higher than that in the control group (P = 0.040). No severe complications were observed in those who received atezolizumab and bevacizumab or other therapy. CONCLUSION: Postoperative adjuvant therapy was related to two-year RFS. TACE, T + A, and the combination of these two approaches were comparable in reducing the early recurrence of HCC without severe complications.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Bevacizumab/uso terapêutico , Estudos Retrospectivos , Quimioembolização Terapêutica/efeitos adversos , HepatectomiaRESUMO
Background: Homeobox B5 (HOXB5) is associated with the poor prognosis of various cancer types. However, the specific mechanism by which HOXB5 promotes the malignant progression of pancreatic cancer (PC) remains to be determined.Methods: The Cancer Genome Atlas database indicated HOXB5 expression level correlated to PC prognosis. The biological functions of HOXB5 was confirmed by colony formation, migration, and invasion assays. The effects of HOXB5 on the expression of cancer stem cell and epithelial-mesenchymal transition markers were evaluated. The downstream target of HOXB5 was miR-6723, which was detected by transcriptional assay. A xenograft tumor model was established in nude mice for the assessment of the role of HOXB5 in tumor growth and metastasis.Results: PC tissues had higher HOXB5 expression levels than noncancerous tissues, and high HOXB5 expression was significantly associated with poor PC prognosis. HOXB5 knockdown suppressed clone formation and the proliferation, invasion, and migration of PC cells in vitro. Conversely, these activities were enhanced by HOXB5 overexpression. The HOXB5 that bound two synergy motifs regulated miR-6723 expression and contributed to PC malignant progression. The role of HOXB5 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that Twist1 and Zeb1 expression levels were increased by HOXB5.Conclusions: HOXB5 overexpression was significantly correlated with poor PC prognosis. HOXB5 accelerated the malignant progression of PC by up-regulating miR-6723, which afforded PC cells stem-like properties and facilitated the epithelial-mesenchymal transition of PC cells.
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Progressão da Doença , Proteínas de Homeodomínio/metabolismo , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Transdução de Sinais , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sequência Conservada/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Metástase Neoplásica , Motivos de Nucleotídeos/genética , Prognóstico , Regiões Promotoras Genéticas/genética , Ligação Proteica , Regulação para Cima/genéticaRESUMO
AIM: To describe the long-term observation of vitrectomy without subretinal hemorrhage (SRH) management for massive vitreous hemorrhage (VH) secondary to polypoidal choroidal vasculopathy (PCV). METHODS: This is a retrospective, consecutive case series. A total of 86 eyes of 86 patients with >14d of massive VH associated with PCV were included. All patients underwent vitrectomy without SRH management, followed by intravitreal ranibizumab injections and/or photodynamic therapy (PDT) as needed. The main outcome measures were best-corrected visual acuity (BCVA), postoperative adverse events and the recurrence of VH. RESULTS: The average follow-up period was 25.5±9.2mo (range 12-35mo). Mean BCVA at baseline (2.16±0.39 logMAR) had improved significantly, both 3mo after surgery (1.42±0.66 logMAR, P<0.001) and by the last visit (1.23±0.74 logMAR, P<0.001). The common postoperative complications included macular subretinal fibrosis in 14 eyes (16.3%) and ciliary body detachment in 4 eyes (4.7%). Nineteen eyes (22.1%) received following treatment with ranibizumab injections without/with PDT, and 15 (17.4%) were resolved. Four eyes (4.7%) had recurrent hemorrhage during the follow-up period. In multiple regression analysis, thicker SRH (beta=0.33, P=0.025) in the preoperative B-scan and the presence of foveal subretinal fibrosis (beta=0.28, P=0.018) in the follow up were associated with poor postoperative BCVA. CONCLUSION: Vitrectomy without SRH management for massive VH secondary to PCV improved/stabilized visual function in the long-term observation. Eyes presenting with thicker SRH preoperatively and forming foveal subretinal fibrosis in the follow-up period tended to have worse BCVA.
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Breast cancer (BC) is a type of malignant tumor originating from the epithelial tissue of the mammary gland, and about 20% of breast cancers are human epidermal growth factor receptor 2 positive (HER2+), which is a subtype with more aggression. Recently, HER2-positive breast cancer is often accompanied by poor prognosis of patients, and targeted therapy showed a promising prospect. To combat this disease, novel therapeutic targets are still needed. Adenylate kinase 4 (AK4) is a member of the adenylate kinase family and is expressed in the mitochondrial matrix. AK4 is involved in multiple cellular functions such as energy metabolism homeostasis. Interestingly, AK4 was observed highly expressed in several tumor tissues, and the involvement of AK4 in cancer development was generally revealed. However, the possible role of AK4 on the growth and development of breast cancer is still unclear. Here, we investigated the possible functions of AK4 on the progression of HER2-positive breast cancer. We found the high expression of AK4 in HER2-positive breast cancer tissues from patients who received surgical treatment. Additionally, AK4 expression levels were obviously correlated with clinical-pathological features, including pTNM stage (P = 0.017) and lymph node metastasis (P = 0.046). We mechanically confirmed that AK4 depletion showed the obvious impairment of cell proliferation and invasion in MCF7 and MDA-MB-231 cells. AK4 also facilitates tumor growth and metastasis of HER2-positive breast cancer in vivo. In conclusion, we identified and mechanically confirmed that AK4 is a novel therapeutic target of HER2-positive breast cancer.
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Adenilato Quinase/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Neoplasias Pulmonares/secundário , Receptor ErbB-2/metabolismo , Animais , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Metástase Linfática , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Caleosin is a common lipid-droplet surface protein, which has the ability to bind calcium. Arabidopsis (Arabidopsis thaliana) is considered a model organism in plant researches. Although there are growing researches about caleosin in the past few years, a systemic analysis of caleosins in Arabidopsis is still scarce. In this study, a comprehensive investigation of caleosins in Arabidopsis was performed by bioinformatics methods. Firstly, eight caleosins in Arabidopsis are divided into two types, L-caleosin and H-caleosin, according to their molecular weights, and these two types of caleosin have many differences in characteristics. Secondly, phylogenetic tree result indicates that L-caleosin may evolve from H-caleosin. Thirdly, duplication pattern analysis shows that segmental and tandem duplication are main reasons for Arabidopsis caleosin expansion with the equal part. Fourthly, the expression profiles of caleosins are also investigated in silico in different organs and under various stresses and hormones. In addition, based on promoter analysis, caleosin may be involved in calcium signal transduction and lipid accumulation. Thus, the classification and expression analysis of caleosin genes in Arabidopsis provide facilities to the research of phylogeny and functions in this gene family.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Proteínas de Ligação ao Cálcio/genética , Genes de Plantas , Proteínas de Plantas/genética , Sequência de Aminoácidos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/classificação , Proteínas de Arabidopsis/metabolismo , Sinalização do Cálcio/genética , Proteínas de Ligação ao Cálcio/classificação , Proteínas de Ligação ao Cálcio/metabolismo , Mapeamento Cromossômico , Evolução Molecular , Duplicação Gênica , Regulação da Expressão Gênica de Plantas , Genômica , Metabolismo dos Lipídeos/genética , Dados de Sequência Molecular , Família Multigênica , Filogenia , Óleos de Plantas/metabolismo , Proteínas de Plantas/classificação , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Homologia de Sequência de AminoácidosRESUMO
BACKGROUND: Psychiatric patients appear to be at lower risk of cancer. Some antipsychotic drugs might have inhibitory effects on tumor growth, including penfluridol, a strong agent. To test this, we conducted a study to determine whether penfluridol exerts cytotoxic effects on tumor cells and, if so, to explore its anti-tumor mechanisms. METHODS: Growth inhibition of mouse cancer cell lines by penfluridol was determined using the 3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was determined by clonogenic cell survival and trypan blue assays. Animal tumor models of these cancer cells were established and to evaluate penfluridol for its anti-tumor efficacy in vivo. Unesterified cholesterol in cancer cells was examined by filipin staining. Serum total cholesterol and tumor total cholesterol were detected using the cholesterol oxidase/p- aminophenazone (CHOD-PAP) method. RESULTS: Penfluridol inhibited the proliferation of B16 melanoma (B16/ F10), LL/2 lung carcinoma (LL/2), CT26 colon carcinoma (CT26) and 4T1 breast cancer (4T1) cells in vitro. In vivo penfluridol was particularly effective at inhibiting LL/2 lung tumor growth, and obviously prolonged the survival time of mice bearing LL/2 lung tumors implanted subcutaneously. Accumulated unesterified cholesterol was found in all of the cancer cells treated with penfluridol, and this effect was most evident in LL/2, 4T1 and CT26 cells. No significant difference in serum cholesterol levels was found between the normal saline-treated mice and the penfluridol-treated mice. However, a dose-dependent decrease of total cholesterol in tumor tissues was observed in penfluridol-treated mice, which was most evident in B16/F10-, LL/2-, and 4T1-tumor-bearing mice. CONCLUSION: Our results suggested that penfluridol is not only cytotoxic to cancer cells in vitro but can also inhibit tumor growth in vivo. Dysregulation of cholesterol homeostasis by penfluridol may be involved in its anti-tumor mechanisms.
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Antipsicóticos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Colesterol/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Penfluridol/uso terapêutico , Animais , Antipsicóticos/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colesterol/sangue , Neoplasias do Colo/metabolismo , Feminino , Homeostase/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Penfluridol/farmacologiaRESUMO
BACKGROUND & AIMS: microRNA-122 is the only identified liver-specific miRNA and plays a crucial role in liver development, maintenance of hepatic homeostasis as well as tumourigenesis. In our previous differentiation of ESCs into hepatocytes, microRNA-122 (miR-122) was expressed at a relatively low level. Here, we aim to elucidate the effect and underlying mechanisms of miR-122 during differentiation of ESCs into hepatocytes. METHODS: Mouse ESCs were initially induced towards HPCs by activin A, FGF-4 and sodium butyrate and were subsequently transfected with a recombinant adenovirus expressing vector pAV.Ex1d-CMV>miR-122/IRES/eGFP 9 days after induction. Cells were analysed by real-time PCR, immunofluorescence, flow cytometry, microscopy and functional assays. Furthermore, microarray analysis was performed. RESULTS: We demonstrated that overexpression of miR-122 could effectively promote hepatic differentiation and maturation, as assessed by morphological and functional tests. The microarray analysis revealed that 323 genes were down-regulated, whereas 59 were up-regulated. Particularly, two liver-specific transcription factors, FoxA1 and HNF4a, were significantly up-regulated. Moreover, the expression of E-cadherin was dramatically increased and the proliferation of HPCs was suppressed, whereas knockdown of FoxA1 reduced E-cadherin expression and increased the proliferation of HPCs. In addition, the expression levels of FoxA1, HNF4a and E-cadherin in time-course transfection experiments with miR-122 were not significantly increased except in cells in which transfection with miR-122 occurred 9 days after induction. CONCLUSION: Overexpression of miR-122 at an appropriate stage could promote hepatic differentiation and maturation by regulating the balance between proliferation and differentiation, as well as the balance between EMT and MET, partially through a miR-122/FoxA1/HNF4a-positive feedback loop.
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Diferenciação Celular/fisiologia , Células-Tronco Embrionárias/citologia , Retroalimentação Fisiológica/fisiologia , Hepatócitos/citologia , MicroRNAs/metabolismo , Animais , Células-Tronco Embrionárias/metabolismo , Citometria de Fluxo , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Fator 4 Nuclear de Hepatócito/metabolismo , Hepatócitos/metabolismo , Camundongos , Análise em Microsséries , Microscopia de Fluorescência , Reação em Cadeia da Polimerase em Tempo RealRESUMO
UNLABELLED: BACKGROUD/AIM: Because of the oncogenic risk, it is important to gain the homogeneous and purified cells from differentiated ESCs before transplantation. Here, we aim to select hepatocyte-like cells from differentiated ESCs, and investigate their growth, differentiation and neoplastic formation after intrahepatic transplantation. METHODS: Mouse ESCs were primarily induced by Dexamethesone, FGF-4 and HGF sequentially, then placed to a conditioning selection media consisting of 5% cholestatic sera and cultivated for 2 wks. After labeled by CFDA-SE, the selected cells were transplanted into mouse liver in therapeutic liver repopulation models. RESULTS: In the early stage of screening cultivation, most cells were suffered from apoptosis or even death. 1w later, some hepatocyte-like colony-forming units were observed, then the selected cells could grow and tend to be more mature, as assessed by morphological and functional tests. After intrahepatic transplantation, the labeled cells could proliferate and expressed albumin. Moreover, teratoma didn't form over 3 months. CONCLUSION: Our conditioning selection media could not only effectively select hepatocyte-like cells from differentiated ESCs, but further promote their growth and differentiation as well. After intrahepatic transplantation in therapeutic liver repopulation models, the selected cells could grow, differentiate and keep partial hepatic function. In particular, the transplantation was safe.
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Diferenciação Celular , Células-Tronco Embrionárias/citologia , Hepatócitos/citologia , Hepatócitos/transplante , Regeneração Hepática , Fígado/citologia , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Dexametasona/farmacologia , Células-Tronco Embrionárias/efeitos dos fármacos , Fator 4 de Crescimento de Fibroblastos/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Transplante de Fígado , Camundongos , Camundongos Endogâmicos , Alcaloides de Pirrolizidina/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Strain M(438), deposited as CGMCC3917 and isolated from inoculums of bacterial cellulose (BC) producing strain screened in homemade vinegar and then induced by high hydrostatic pressure treatment (HHP), has strong ability to produce BC more than three times as that of its initial strain. It is the highest yield BC-producing strain ever reported. In this paper, M(438) was identidied as Gluconacetobacter hansenii subsp. nov. on the basis of the results obtained by examining it phylogenetically, phenotypically, and physiologically-biochemically. Furthermore, the genetic diversity of strain M(438) and its initial strain was examined by amplified fragment length polymorphism. The results indicated that strain M(438) was a deletion mutant induced by HHP, and the only deleted sequence showed 99% identity with 24,917-24,723 bp in the genome sequence of Ga. hansenii ATCC23769, and the complement gene sequence was at 24,699-25,019 bp with local tag GXY_15142, which codes small multidrug resistance (SMR) protein. It can be inferred that SMR might be related to inhibiting BC production to a certain extent.