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1.
Inflamm Res ; 73(1): 65-82, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38062164

RESUMO

BACKGROUND: Atherosclerosis, characterized by abnormal arterial lipid deposition, is an age-dependent inflammatory disease and contributes to elevated morbidity and mortality. Senescent foamy macrophages are considered to be deleterious at all stages of atherosclerosis, while the underlying mechanisms remain largely unknown. In this study, we aimed to explore the senescence-related genes in macrophages diagnosis for atherosclerotic plaque progression. METHODS: The atherosclerosis-related datasets were retrieved from the Gene Expression Omnibus (GEO) database, and cellular senescence-associated genes were acquired from the CellAge database. R package Limma was used to screen out the differentially expressed senescence-related genes (DE-SRGs), and then three machine learning algorithms were applied to determine the hub DE-SRGs. Next, we established a nomogram model to further confirm the clinical significance of hub DE-SRGs. Finally, we validated the expression of hub SRG ABI3 by Sc-RNA seq analysis and explored the underlying mechanism of ABI3 in THP-1-derived macrophages and mouse atherosclerotic lesions. RESULTS: A total of 15 DE-SRGs were identified in macrophage-rich plaques, with five hub DE-SRGs (ABI3, CAV1, NINJ1, Nox4 and YAP1) were further screened using three machine learning algorithms. Subsequently, a nomogram predictive model confirmed the high validity of the five hub DE-SRGs for evaluating atherosclerotic plaque progression. Further, the ABI3 expression was upregulated in macrophages of advanced plaques and senescent THP-1-derived macrophages, which was consistent with the bioinformatics analysis. ABI3 knockdown abolished macrophage senescence, and the NF-κB signaling pathway contributed to ABI3-mediated macrophage senescence. CONCLUSION: We identified five cellular senescence-associated genes for atherogenesis progression and unveiled that ABI3 might promote macrophage senescence via activation of the NF-κB pathway in atherogenesis progression, which proposes new preventive and therapeutic strategies of senolytic agents for atherosclerosis.


Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Camundongos , Aterosclerose/genética , Aterosclerose/metabolismo , Macrófagos/metabolismo , NF-kappa B/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Transdução de Sinais
2.
Acta Haematol ; 146(6): 517-521, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37634507

RESUMO

INTRODUCTION: The purpose of this study was to examine the effect of iron overload on the mobilization of peripheral blood stem cells (PBSCs) in pediatric patients with ß-thalassemia major (TM). METHODS: We retrospectively reviewed the records of 226 patients with TM from whom PBSCs were collected. Iron overload was based on serum ferritin level, and liver and cardiac iron overload was measured by magnetic resonance imaging (MRI) T2*. RESULTS: The mean age of the TM patients was 7.35 ± 3.41 years. Of the patients, only 171 received MRI. Of the 171 patients, 35 had normal liver iron levels, 39 mild liver iron overload, 90 intermediate liver iron overload, and 7 severe liver iron overload. The intermediate + severe group was associated with significantly higher age and BMI and lower leukapheresis product white blood cell count and CD34+ cell levels (all, p < 0.05). CONCLUSION: Leukapheresis indices were similar between patients with different degrees of iron overload according to the ferritin level and cardiac iron overload, in which the later might be due to the small number of patients with cardiac overload. In patients with TM, the intermediate and severe liver iron overload was associated with poorer mobilization of PBSCs.


Assuntos
Sobrecarga de Ferro , Células-Tronco de Sangue Periférico , Talassemia beta , Humanos , Criança , Pré-Escolar , Talassemia beta/complicações , Talassemia beta/terapia , Ferritinas , Estudos Retrospectivos , Células-Tronco de Sangue Periférico/metabolismo , Células-Tronco de Sangue Periférico/patologia , Fígado/metabolismo , Imageamento por Ressonância Magnética/métodos , Miocárdio
3.
Infect Dis Ther ; 12(8): 2071-2086, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37470925

RESUMO

INTRODUCTION: Since hematopoietic stem cell transplant (HSCT) is an important therapy for malignant and non-malignant pediatric diseases, improving transplant-related mortality remains a challenge. Currently, rituximab, a monoclonal antibody of anti-CD20, is widely used for several post-HSCT complications. However, few studies have focused on the application of rituximab before HSCT. METHODS: We conducted a retrospective case-control study from January 2019 to July 2021 to determine this effect in a single center. Forty-eight patients were included in the rituximab group, with a one-to-one ratio matched to the control group. RESULTS: Both the occurrence rate and cumulative incidence rate of Epstein-Barr virus (EBV) infection were significantly lower in the rituximab group than in the without-rituximab group (10.4% vs. 33.3%, p = 0.014 and 12.2% vs. 39.3% p = 0.0026, respectively). Furthermore, without the application of rituximab was identified as a risk factor for post-HSCT EBV infection via both univariate [hazard ratio (HR) = 4.17, 95%CI (1.52-11.43), p = 0.005] and multivariate analyses [HR = 4.65, 95%CI (1.66-13.0), p = 0.003]. Although the overall survival (OS) probability of the rituximab group was comparable to the without-rituximab group, a markedly improved OS of the rituximab group was found in the malignant disease subgroup (78.9% vs. 42.1%, p = 0.032). The outcomes of graft-versus-host disease, neutrophil and platelet engraftment, other viral infections, and the reconstitution of lymphocytes showed no significant differences between the two groups. CONCLUSIONS: The administration of rituximab before HSCT may prevent EBV infection following HSCT.

4.
Macromol Rapid Commun ; 44(23): e2300192, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37194368

RESUMO

Microspheres bearing large pores are useful in the capture and separation of biomolecules. However, pore size is typically poorly controlled, leading to disordered porous structures with limited performances. Herein, ordered porous spheres with a layer of cations on the internal surface of the nanopores are facilely fabricated in a single step for effective loading of DNA bearing negative charges. Triblock bottlebrush copolymers (BBCPs), (polynorbornene-g-polystyrene)-b-(polynorbornene-g-polyethylene oxide)-b-(polynorbornene-g-bromoethane) (PNPS-b-PNPEO-b-PNBr), are designed and synthesized for fabrication of the positively charged porous spheres through self-assembly and in situ quaternization during an organized spontaneous emulsification (OSE) process. Pore diameter as well as charge density increase with the increase of PNBr content, resulting in a significant increase of loading density from 4.79 to 22.5 ng µg-1 within the spheres. This work provides a general strategy for efficient loading and encapsulation of DNA, which may be extended to a variety of different areas for different real applications.


Assuntos
Polietilenoglicóis , Polímeros , Polímeros/química , Polietilenoglicóis/química , Poliestirenos/química , Propriedades de Superfície , DNA
5.
Front Pediatr ; 11: 1099372, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873638

RESUMO

Thrombocytopenia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common and life-threatening complication. Thus, new prevention and treatment strategies for post-HSCT thrombocytopenia are urgently required. In recent studies, thrombopoietin receptor agonists (TPO-RA) for treating post-HSCT thrombocytopenia indicated efficiency and safety. The improved effect of post-HSCT thrombocytopenia in adults was found in the administration of avatrombopag which was a new TPO-RA. However, there was no relevant study in the children's cohort. Herein, we retrospectively analyzed the effect of avatrombopag in post-HSCT thrombocytopenia in children. As a result, the overall response rate (ORR) and complete response rate (CRR) were 91% and 78%, respectively. Furthermore, both cumulative ORR and CRR were significantly lower in the poor graft function (PGF)/secondary failure of platelet recovery (SFPR) group compared to the engraftment-promotion group (86.7% vs. 100%, p = 0.002 and 65.0% vs. 100%, p < 0.001, respectively). Achieving OR required a median of 16 days in the PGF/SFPR group while 7 days in the engraftment-promotion group (p = 0.003). Grade III-IV acute graft vs. host disease and inadequate megakaryocytes were identified as risk factors of CRR only in univariate analysis (p = 0.03 and p = 0.01, respectively). No severe adverse events were documented. Conclusively, avatrombopag is an alternatively efficient and safe agent for treating post-HSCT thrombocytopenia in children.

6.
Front Cell Infect Microbiol ; 12: 1027341, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339340

RESUMO

Cytomegalovirus (CMV) infection remains a critical cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), despite improvement by pre-emptive antivirus treatment. CMV-specific cytotoxic T lymphocytes (CMV-CTL) are universally used and proven well-tolerance after allo-HSCT in adult clinical trials. However, it is not comprehensively evaluated in children's patients. Herein, we conducted a retrospective study to determine the risk factors of CMV infection and evaluation of CMV-CTL in children patients who underwent allo-HSCT. As result, a significantly poor 5-year overall survival was found in the CMV infection group (87.3 vs. 94.6%, p=0.01). Haploidentical HSCT (haplo-HSCT) was identified as an independent risk factor for CMV infection through both univariate and multivariate analyses (p<0.001, p=0.027, respectively). Furthermore, the cumulative incidence of CMV infection was statistically higher in the haplo-HSCT group compared to the HLA-matched donor group (44.2% vs. 21.6%, p<0.001). Finally, the overall response rate of CMV-CTL was 89.7% (26/29 patients) in CMV infection after allo-HSCT. We concluded that CMV infection following allo-HSCT correlated with increased mortality in children's patients, and haplo-HSCT was an independent risk factor for CMV infection. Adoptive CMV-CTL cell therapy was safe and effective in pediatric patients with CMV infection.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Criança , Citomegalovirus , Estudos Retrospectivos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfócitos T
7.
Angew Chem Int Ed Engl ; 61(5): e202113759, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-34859551

RESUMO

Artificial self-assembly systems typically exhibit limited capability in creating nature-inspired complex materials with advanced functionalities. Here, an effective co-assembly strategy is demonstrated for the facile creation of complex photonic structures with intriguing light reflections. Two different lipophilic and amphiphilic bottlebrush block copolymers (BCPs) are placed within shrinking droplets to enable a cooperative working mechanism of microphase segregation and organized spontaneous emulsification, respectively. Layer assemblies of the lipophilic BCP and uniform water nanodroplets stabilized by the bottlebrush surfactant are both generated, and co-assembled into a bridged lamellar structure with the alternating arrangement of layers and closely packed nanodroplet arrays. Janus microspheres with diverse dual optical characteristics are successfully fabricated, and reflected wavelengths of light are highly tunable simply by changing the formulation or molecular weight of BCP.

8.
Nanotechnology ; 32(43)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34284371

RESUMO

The development of visible light photocatalysts with the ability to efficiently degrade pollutants is an important measure to solve environmental problems. In this paper, Cu2+doped TiO2-SiO2(CTS) with photonic crystal structure composite was successfully synthesized via sol-gel strategy and template method. The prepared materials have abundant pore structure and uniform pore diameter, and the pores were arranged in a periodically hexagonal structure. It showed enhancing synergistic effect of adsorption-photodegradation ability for removing Rhodamine B (RhB). The brilliant adsorption capability of the catalyst is not only due to the addition of silica which can increase surface area that results the increase in adsorption ability, but also related to the rich and ordered porous structure provided by the photonic crystal. The catalyst has a narrow band gap ∼2.92 eV which exhibits the excellent photocatalytic activity for RhB degradation (>95% at 30 min) under visible light irradiation, and possesses higher photocatalytic reaction apparent rate constants (k) which is 7 folds higher than that of pure TiO2. The excellent photocatalytic performance is attributed to the Cu2+doping that narrows the band gap, increases light absorption, and promotes charge separation. Besides, the constructed photonic crystal structure not only further enhances charge transport but also provides more surface activity sites for photocatalytic reactions. More importantly, the ordered pore structure-photonic crystal can prolong the interaction time between light and catalyst through the slow photon effect and the porous scattering effect. Eventually, the photocatalytic degradation efficiency of the catalyst was significantly improved by the synergistic effect of the above mechanisms.

9.
Langmuir ; 37(22): 6744-6753, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34036783

RESUMO

Solvent-free supersoft elastomer is highly desirable for building photonic structures with significant stimuli-responsive color changes. We report supersoft elastic porous microspheres with vivid structural colors obtained via self-assembly of amphiphilic bottlebrush block copolymers at the water/oil interface templated by ordered water-in-oil-in-water double emulsions. The porous structure is composed of cross-linked bottlebrush polydimethylsiloxane (PDMS) as the supersoft elastic skeleton and bottlebrush poly(ethylene oxide) (PEO) as the internal responsive layer. The obtained microspheres show large reversible volume changes through well-controlled dehydration or hydration of PEO in response to salt ions in an aqueous environment. As a result, full-spectrum colors are obtained dependent on different salt concentrations. In-situ observation of color reflection of a microsphere indicates a gradual structural transition from the outside to the inside corresponding to migration of water molecules and salt ions. Moreover, rod-like bottlebrush PEO exhibits an anion-induced salting-out behavior different from that of random coil polymers. The significantly responsive behaviors of bottlebrush block copolymer (BBCP) assemblies in the presence of salt ions primarily rely on the supersoft elastic skeleton of the porous structure, providing a facile route to the creation of stimuli-responsive photonic materials by low-cost self-assembly methods.

10.
Med Sci Monit ; 27: e930591, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33723203

RESUMO

BACKGROUND Cytochrome P450 (CYP) genes are necessary for the production or metabolism of fetal sex hormones during pregnancy. The second-to-fourth digit ratio (2D: 4D) is formed in the early stage of human fetal development and considered an indicator reflecting prenatal sex steroids levels. We explored the association between 2D: 4D and single-nucleotide polymorphisms (SNPs) of CYP. MATERIAL AND METHODS Correlation analysis between 2D: 4D and 8 SNPs, rs2687133 (CPY3A7), rs7173655 (CYP11A1), rs1004467, rs17115149, and rs2486758 (CYP17A1), and rs4646, rs2255192, rs4275794 (CYP19A1), was performed using data from 426 female and 412 male Chinese university students. SNP genotyping was conducted using PCR. Digit lengths were photographed and measured by image processing software. RESULTS rs2486758 (CYP17A1) correlated with left hand 2D: 4D in men (P=0.026), and rs1004467 (CYP17A1) correlated with right hand 2D: 4D in men (P=0.008) and the whole population (P=0.032). In men, allele G rs1004467 decreased right hand 2D: 4D, while allele C of rs2486758 increased left hand 2D: 4D. In women, left hand 2D: 4D was higher in genotypes with allele A of SNP rs4646 (CYP19A1) under the dominant genetic model; female DR-L was higher in genotypes with allele T of rs17115149 (CYP11A1). SNPs rs2687133 (CYP3A7) and rs1004467 (CYP17A1) were significantly correlated with right hand 2D: 4D (P=0.0107). CONCLUSIONS SNPs rs1004467 and rs2486758 of CYP17A1 are significant in the relationship between 2D: 4D and CYP gene polymorphisms under different conditions. SNP interactions between CYP genes probably impact 2D: 4D. The correlation between 2D: 4D and some sex hormone-related diseases may be due to the effect of CYP variants on the 2 phenotypes.


Assuntos
Sistema Enzimático do Citocromo P-450 , Dedos , Feminino , Humanos , Masculino , Adulto Jovem , Alelos , Aromatase/genética , Povo Asiático/genética , Estudos de Casos e Controles , China , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Citocromo P-450 CYP3A/genética , Sistema Enzimático do Citocromo P-450/genética , Dedos/anatomia & histologia , Frequência do Gene/genética , Estudos de Associação Genética/métodos , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Esteroide 17-alfa-Hidroxilase/genética , Estudantes , Universidades
11.
ACS Nano ; 15(3): 5534-5544, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33625825

RESUMO

Ultratrace quantitative detection based on fluorescence is highly desirable for many important applications such as environmental monitoring or disease diagnosis, which however has remained a great challenge because of limited and irregular fluorescence responses to analytes at ultralow concentrations. Herein the problem is circumvented via local enrichment and detection of analytes within a microsensor, that is, photonic porous microspheres grafted with aggregation-induced emission gens (AIEgens). The obtained microspheres exhibit dual structural and molecular functions, namely, bright structural colors and strong fluorescence. Large fluorescence quenching induced by nitrophenol compounds in an aqueous environment is observed at ultralow concentrations (10-12-10-8 mol/L), enabling quantitative detection at a ppb level (ng/L). This is achieved within a porous structure with good connectivity between the nanopores to improve analyte diffusion, an internal layer of poly(ethylene oxide) (PEO) for analyte enrichment via hydrogen bonding, and homogeneous distribution of AIEgens within the PEO layer for enhanced fluorescence quenching. The fluorescent porous microspheres can be readily obtained in a single step templated by well-ordered water-in-oil-in-water double emulsion droplets with AIE amphiphilic bottlebrush block copolymers as the effective stabilizer.


Assuntos
Polietilenoglicóis , Polímeros , Emulsões , Fluorescência , Microesferas
12.
Oncol Lett ; 15(4): 5781-5786, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29545903

RESUMO

There is limited knowledge regarding the influence of autophagy on the anticancer effect of dihydroartemisinin (DHA). The present study aimed to investigate this influence within human breast cancer cells. Changes in cell viability, cell cycle distribution, apoptosis and associated genes were analyzed in MDA-MB-231 cells subjected to DHA following alteration in autophagy levels; the autophagy level was decreased following autophagy-related 7 (Atg7) knockdown or increased using rapamycin. The data indicated that rapamycin had the ability to notably enhance the anticancer effect of DHA on MDA-MB-231 cells. Autophagy induction may be key in mediating the anticancer effects of DHA, and rapamycin may regulate the death-associated protein kinase via the alteration of Atg7 expression, which would influence cell apoptosis. The present study presented a novel insight into enhancing the effectiveness of future treatment regimens for breast cancer using DHA.

13.
Macromol Rapid Commun ; 39(9): e1700869, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29527746

RESUMO

Circularly polarized luminescence (CPL) induced by host-guest complexation remains a challenge in supramolecular chemistry. Herein, a couple of CPL-silent enantiomeric guest binaphthylbis(4,4'-bipyridinium) salts can emit obvious CPL in the presence of cucurbit[8]uril in aqueous media, due to the restriction of molecular rotation limitation effect. Such CPL can be reversibly adjusted by the addition of acid and base. Furthermore, the resultant supramolecular systems can interact with DNA, accompanied by the morphological conversion from branched supramolecular nanowires to exfoliated nanowires, which can enable to the exploration of such supramolecular systems as DNA markers by CPL signals.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Medições Luminescentes , Piridinas/química , Dicroísmo Circular , Luminescência , Estereoisomerismo
14.
Cytogenet Genome Res ; 151(2): 72-81, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28433994

RESUMO

Integrating gammaretroviral vectors can dysregulate the expression of cellular genes through a variety of mechanisms, leading to genotoxicity and malignant transformation. Although most attention has focused on the activation of cellular genes by vector enhancers, aberrant fusion transcripts involving cellular gene sequences and vector promoters, vector splice elements, and vector transcription termination sequences have also been mechanistically associated with dysregulated expression of cellular genes. Chromatin insulators have emerged as an effective tool for reducing the frequency of vector-mediated genotoxicity and malignant transformation and have been shown to block the activation of cellular genes by vector enhancers. We report here evidence that flanking a gammaretroviral reporter vector with the cHS4 chromatin insulator also reduces the frequency of vector-mediated cellular gene dysregulation associated with aberrant vector transcripts, including vector transcription run-through and aberrant splicing. We demonstrate that the cHS4 element does not function to terminate transcription directly, implicating other mechanisms for this activity.


Assuntos
Cromatina/genética , Vetores Genéticos , Elementos Isolantes , Retroviridae/genética , Transcrição Gênica , Processamento Alternativo , Linhagem Celular , Dosagem de Genes , Regulação da Expressão Gênica , Proteínas de Fluorescência Verde/genética , Humanos
15.
Oncol Lett ; 8(6): 2543-2548, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25364424

RESUMO

In the last decade, the overexpression of hepatoma upregulated protein (HURP) has been reported in hepatocellular carcinoma, adrenocortical tumors and urogenital carcinoma. However, the role of HURP in breast cancer remains unknown. In the present study, a comprehensive analysis was performed to examine the HURP expression level in 43 breast cancer tumor samples and paired adjacent normal tissues. The correlation between the HURP expression level and the clinicopathological characteristics was evaluated. The role of HURP in breast cancer was investigated by quantitative polymerase chain reaction, western blot analysis and cell proliferation assays. HURP expression was found to be significantly increased in the breast cancer samples. The HURP expression level was higher in the tumors with advanced-grade metastasis and was strongly associated with tumor-node-metastasis staging (P=0.003). Transfection and cell proliferation assays suggested that the suppression of HURP expression or the interference in HURP activity in the breast cancer cells inhibited cell proliferation significantly. These data suggest that HURP is associated with the degree of malignancy and the proliferation of breast cancer. HURP could be a tumor biomarker for prognosis and a potential therapeutic drug target for human breast cancer.

16.
Mol Cell Biochem ; 396(1-2): 67-77, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25148870

RESUMO

Hypermethylation of promoter CpG islands represents an alternative mechanism to inactivate tumor suppressor genes. This study was to detect promoter methylation status and mRNA expression levels of ARRDC3, ELP3, GATA5, and PAX6, and to explore the association between methylation and expression in invasive ductal carcinomas (IDCs) and matched normal tissues (MNTs) from breast cancer patients. Aberrant gene methylation was observed as follows: ARRDC3 in 38.5 %, ELP3 in 73.1 %, GATA5 in 48.1 %, and PAX6 in 50.0 % of IDCs. mRNA expression of ARRDC3, ELP3, and GATA5 in IDCs showed a lower level than that in MNTs (P < 0.001, P = 0.001 and P < 0.001, respectively). For ARRDC3, both methylated and unmethylated IDCs showed significantly lower expression values compared to MNTs (P = 0.001 and P = 0.007, respectively). For ELP3 and GATA5, methylated tumors only showed significantly lower expression values compared to MNTs (P = 0.001 and P < 0.001, respectively). For ARRDC3 and GATA5, methylation was associated with their less fold change in IDCs (P = 0.049 and P = 0.020, respectively). Methylation of ARRDC3 was significantly associated with grades and lymph node status of IDCs (P = 0.036 and P = 0.002, respectively). Methylation frequency of ELP3 was higher in lymph node positive versus lymph node negative tumors (P = 0.020); whereas methylation frequency of PAX6 was lower in tumors with the ER negative samples (P = 0.025). Our data suggested that promoter hypermethylation may be an important mechanism of the transcriptional inactivation of ARRDC3, GATA5, and ELP3 in IDCs.


Assuntos
Arrestinas/genética , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Fator de Transcrição GATA5/genética , Histona Acetiltransferases/genética , Proteínas do Tecido Nervoso/genética , Regiões Promotoras Genéticas , Adulto , Idoso , Povo Asiático , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Metilação de DNA , Proteínas do Olho/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Proteínas de Homeodomínio/genética , Humanos , Metástase Linfática/genética , Pessoa de Meia-Idade , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/genética , Valores de Referência , Proteínas Repressoras/genética
17.
Mol Med Rep ; 10(2): 625-30, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24898397

RESUMO

Atg7 is an autophagy­related gene, and is involved in two ubiquitin­like conjugation systems in the process of autophagy. It is well established that 3­methyladenine (3Ma) is an autophagy inhibitor. The present study aimed to investigate the effect of autophagy inhibition on the cell viability and cell cycle progression of human breast cancer cells. MDA­MB­231 human breast cancer cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with high glucose, then divided into six groups. The six groups included the three fundamental groups as follows: The control group (untreated); the starvation group (high­glucose DMEM replaced with glucose­free minimal essential medium); and the starvation 3Ma group (maintained in glucose­free culture medium and treated with the autophagy inhibitor 3Ma). The three fundamental groups were further divided into Atg7 siRNA­transfected and non­transfected groups. The cell viability and apoptosis of each group was determined by MTT assay and flow cytometry. The results of the current study demonstrated that Atg7 deficiency alone had no statically significant effect on the cell viability of MDA­MB­231 human breast cancer cells, while 3Ma reduced the cell viability and its effect was potentiated by Atg7 deficiency. Atg7 deficiency was more intense than 3Ma in the promotion of apoptosis and cell arrest in G0/G1­phase in the absence of glucose and its effect was reduced by 3Ma. In conclusion, 3Ma and Atg7 may be involved in different pathways in the process of autophagy. Inhibition of autophagy may influence the cell viability and cell cycle through different pathways in MDA­MB­231 human breast cancer cells.


Assuntos
Autofagia , Enzimas Ativadoras de Ubiquitina/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Apoptose/efeitos dos fármacos , Proteína 7 Relacionada à Autofagia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Enzimas Ativadoras de Ubiquitina/antagonistas & inibidores , Enzimas Ativadoras de Ubiquitina/genética
18.
Med Hypotheses ; 82(3): 398-400, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24491427

RESUMO

Hepatocellular carcinoma (HCC) is a highly deadly cancer, with usually drug resistance. However the mechanisms responsible for this phenomenon are poorly understood. Interferon-γ inducible protein 16 (IFI16), a multifunctional protein, has roles in anti-proliferation, autophagy, cell senescence, anti-inflammation, and DNA sensor to trigger innate immunity. IFI16 physiologically absents in adult healthy hepatocyte, but exists in liver cancer cells. Interestingly, increasing evidences suggest that dysregulation or/and loss of IFI16 function have a critical role in drug resistance and tumor progression. Furthermore, interaction with DNA or other protein depends on IFI16 localization. In our study, to our knowledge, we first showed that IFI16 is a chromatin-binding protein in four HCC cell lines with different TP53 genotype, but not in fetal liver cell line, L02 cells. However, the function of IFI16 subcellular localization has not been determined in HCC. Therefore, we present our study and theoretical basis and presume that chromatin-bounding localization of IFI16 is associated with HCC progression. If we are able to acetylate or/and delete NLS of IFI16 with activated-p53 restoration, we may offer an alternative for HCC therapy.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Sequência de Bases , Carcinoma Hepatocelular/metabolismo , Cromatina/metabolismo , Primers do DNA , Progressão da Doença , Humanos , Neoplasias Hepáticas/metabolismo , Modelos Teóricos , Proteínas Nucleares/genética , Fosfoproteínas/genética , Frações Subcelulares/metabolismo
19.
Blood ; 120(19): 3875-81, 2012 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-22968457

RESUMO

We used a novel NF-08-TM transplant protocol based on intravenous busulfan, cyclophosphamide, fludarabine, and thiotepa in 82 consecutive patients with ß-thalassemia major (TM), including 52 with allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors (UDs) with well-matched human leukocyte antigens and 30 with hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs). The median age at transplantation was 6.0 years (range, 0.6-15.0 years), and the ratio of male-to-female patients was 56:26. The median follow-up time was 24 months (range, 12-39 months). The estimated 3-year overall survival and TM-free survival were 92.3% and 90.4% in the UD-PBSCT group and 90.0% and 83.3% in the MSD-HSCT group. The cumulative incidences of graft rejection and grades III-IV acute graft-versus-host disease were 1.9% and 9.6%, respectively, in the UD-PBSCT group and 6.9% and 3.6%, respectively, in the MSD-HSCT group. The cumulative incidence of transplant-related mortality was 7.7% in the UD-PBSCT group and 10.0% in the MSD-HSCT group. In conclusion, UD-PBSCTs using the well-tolerated NF-08-TM protocol show similar results to MSD-HSCTs and can be used to treat ß-thalassemia patients in the absence of MSDs.


Assuntos
Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Doadores não Relacionados , Talassemia beta/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Resultado do Tratamento , Adulto Jovem , Talassemia beta/complicações , Talassemia beta/mortalidade
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(10): 2810-4, 2009 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-20038066

RESUMO

Pyrazoline derivatives have been used widely in dyeing industry as fluorescent whitening agents due to their excellent capability. According to Schellhammer theory of the relation between chemical structure and fluorescent quality, six new fluorescent compounds were designed and synthesized which contained the benzothiazole group in the 1-pyrazoline, the indole group in the 3-pyrazoline and the derivatives of phenyl in the 5-pyrazoline. The structure of target compounds was confirmed by IR, 1H NMR, MS and elementary analysis. The fluorescence spectra showed that these compounds had good fluorescence. They could absorb ultraviolet light at near 353 nm. The fluorescence maximum emission wavelengths were about 430-443 nm. It was a kind of promising fluorescence compounds. The largest fluorescence emission wavelength and the fluorescence intensity were related to the substituted group of the compounds. When the 6-Br group was introduced into benzothiazole, the fluorescence emission wavelength exhibited a blue shift, and the fluorescence intensity increased. Otherwise, the CH3 group was introduced into benzothiazole, the fluorescence emission wavelength red-shift occurred, and the intensity was lower. The fluorescence quantum yield of the compounds was little affected by the substituted group and polarity of the solvent The relative fluorescence intensity and fluorescence quantum yield were not directly related.

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