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Ovarian cancer is the leading cause of death from female gynecological cancers. Cisplatin (DDP) is a first-line drug for ovarian cancer treatment. Due to DDP resistance, there is an urgent need for novel therapeutic drugs with improved antitumor activity. AMPK-mediated metabolic regulatory pathways are related to tumor drug resistance. Our study aimed to determine the relationship between reversing DDP resistance with the anthraquinone derivative KA-4s and regulating AMPK energy metabolism in ovarian cancer. The results showed that KA-4s inhibited the proliferation of ovarian cancer cells. The combination of KA-4s with DDP effectively promoted drug-resistant ovarian cancer cell apoptosis and inhibited cell migration and invasion. Moreover, KA-4s decreased the intracellular ATP level and increased the calcium ion level, leading to AMPK phosphorylation. Further studies suggested that the AMPK signaling pathway may be involved in the mechanism through which KA-4s reduce drug resistance. KA-4s inhibited mitochondrial respiration and glycolysis; downregulated the glucose metabolism-related proteins GLUT1 and GLUT4; the lipid metabolism-related proteins SREBP1 and SCD1; and the drug resistance-related proteins P-gp, MRP1, and LRP. The inhibitory effect of KA-4s on GLUT1 was confirmed by the application of the GLUT1 inhibitor BAY-876. KA-4s combined with DDP significantly increased the expression of p-AMPK and reduced the expression of P-gp. In a xenograft model of ovarian cancer, treatment with KA-4s combined with DDP reduced energy metabolism and drug resistance, inducing tumor apoptosis. Consequently, KA-4s might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of treatment for ovarian cancer.
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Gonadal soma-derived factor (gsdf) has been demonstrated to be essential for testicular differentiation in medaka (Oryzias latipes). To understand the protein dynamics of Gsdf in spermatogenesis regulation, we used a His-tag "pull-down" assay coupled with shotgun LC-MS/MS to identify a group of potential interacting partners for Gsdf, which included cytoplasmic dynein light chain 2, eukaryotic polypeptide elongation factor 1 alpha (eEF1α), and actin filaments in the mature medaka testis. As for the interaction with transforming growth factor ß-dynein being critical for spermatogonial division in Drosophila melanogaster, the physical interactions of Gsdf-dynein and Gsdf-eEF1α were identified through a yeast 2-hybrid screening of an adult testis cDNA library using Gsdf as bait, which were verified by a paired yeast 2-hybrid assay. Coimmunoprecipitation of Gsdf and eEF1α was defined in adult testes as supporting the requirement of a Gsdf and eEF1α interaction in testis development. Proteomics analysis (data are available via ProteomeXchange with identifier PXD022153) and ultrastructural observations showed that Gsdf deficiency activated eEF1α-mediated protein synthesis and ribosomal biogenesis, which in turn led to the differentiation of undifferentiated germ cells. Thus, our results provide a framework and new insight into the coordination of a Gsdf (transforming growth factor ß) and eEF1α complex in the basic processes of germ cell proliferation, transcriptional and translational control of sexual RNA, which may be fundamentally conserved across the phyla during sexual differentiation.
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Proteínas de Peixes/metabolismo , Células Germinativas/citologia , Oryzias/metabolismo , Fator 1 de Elongação de Peptídeos/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Animais Geneticamente Modificados , Proliferação de Células , Feminino , Masculino , Oryzias/genética , Proteômica , RNA/metabolismo , Testículo/citologia , Testículo/metabolismo , Testículo/ultraestrutura , Fator de Crescimento Transformador beta/genéticaRESUMO
The ubiquitin-proteasome system is the primary cellular pathway for protein degradation, mediating 80% of intracellular protein degradation. Because of the widespread presence of ubiquitin-modified protein substrates, ubiquitination can regulate a variety of cellular activities including cell proliferation, apoptosis, autophagy, endocytosis, DNA damage repair, and immune responses. With the continuous generation of genomics data in recent years it has become particularly important to analyze these data effectively and reasonably. Cacybp forms a complex with the E3 ubiquitinated ligase Siah1 to participate in ubiquitination. We analyzed Cacybp-associated genes using the Gene Expression Omnibus (GEO) and CGGA (Chinese Glioma Genome Atlas) databases and identified 121 differentially expressed genes (DEGs), of which 46 were downregulated and 75 were upregulated. The biological processes, molecular functions, and protein-protein interaction (PPI) network of differential genes were analyzed by Cytoscape software and STRING software. We found no difference in Cacybp expression among different grades of gliomas and there was no significant association between the expression level of Cacybp and the prognosis of patients with glioma in LGG and GBM. © 2019 IUBMB Life, 1-8, 2019.
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Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/metabolismo , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Glioma/metabolismo , Proteínas de Ligação ao Cálcio/genética , Bases de Dados Factuais , Feminino , Perfilação da Expressão Gênica , Glioma/genética , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Mapas de Interação de Proteínas , Taxa de SobrevidaRESUMO
Gonadal soma-derived factor (Gsdf) is a unique TGF-ß factor essential for both ovarian and testicular development in Hd-rR medaka (Oryzias latipes). However, the downstream genes regulated by Gsdf signaling remain unknown. Using a high-throughput proteomic approach, we identified a significant increase in the expression of the RNA-binding protein Igf2bp3 in gsdf-deficient ovaries. We verified this difference in transcription and protein expression against normal gonads using real-time PCR quantification and Western blotting. The genomic structure of igf2bp3 and the syntenic flanking segments are highly conserved across fish and mammals. igf2bp3 expression was correlated with oocyte development, which is consistent with the expression of the igf2bp3 ortholog Vg1-RBP/Vera in Xenopus. In contrast to the normal ovary, cysts of H3K27me3- and Igf2bp3-positive germ cells were dramatically increased in the one-month-old gsdf-deficient ovary, indicating that the gsdf depletion led to a dysregulation of Igf2bp3-mediated oocyte development. Our results provide novel insights into the Gsdf-Igf2bp3 signaling mechanisms that underlie the fundamental process of gametogenesis; these mechanisms may be well conserved across phyla.
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Regulação da Expressão Gênica no Desenvolvimento , Oócitos/metabolismo , Oryzias/genética , Proteínas de Ligação a RNA/genética , Fator de Crescimento Transformador beta/deficiência , Sequência de Aminoácidos , Animais , Proliferação de Células , Sequência Conservada , Evolução Molecular , Feminino , Perfilação da Expressão Gênica , Histonas/metabolismo , Lisina/metabolismo , Masculino , Oogênese/genética , Ovário/embriologia , Ovário/metabolismo , Filogenia , Proteômica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Acute lymphoblastic leukemia (ALL) is the commonest childhood malignancy. Despite therapeutic advancements, relapse of the pathological state in the form of central nervous system (CNS) disease remains a challenge. CNS disease appears to be present at diagnosis in at least 40% of patients. This relapse in the form of CNS disease is one of the major hurdles in achieving complete cure. The present review article aims to discuss the important mechanisms of leukemic entry and infiltration patterns of leukemic cells into the CNS. Also, latest updates in the management strategies of ALL will also be focused in the present article.
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Neoplasias do Sistema Nervoso Central/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/terapia , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Resultado do TratamentoRESUMO
Clethramycin (1) and mediomycin A (2) belong to the linear polyene polyketide (LPP) family of antibiotics that exhibit potent antifungal activity. Structural similarities exist between 1 and 2, except that 2 contains an amino moiety substituted for the guanidino moiety. Herein, the draft genome sequence of Streptomyces mediocidicus ATCC23936, a strain which produces both 1 and 2, was obtained through de novo sequencing. Bioinformatic analysis of the genome revealed a clethramycin (cle) gene cluster that contained 25 open reading frames (orfs). However, amidinohydrolase for 2 formation was not found in the cle gene cluster. Further genomic analysis revealed an amidinohydrolase MedX, which can hydrolyse the guanidino form (1) into the amino form (2) via heterologous co-expression of the cle cluster in Streptomyces lividans or by in vitro catalysis. These results also suggest the feasibility of engineering novel LPPs for drug discovery by manipulating the biosynthetic machinery of S. mediocidicus.
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Amidoidrolases/metabolismo , Antifúngicos/metabolismo , Proteínas de Bactérias/metabolismo , Polienos/metabolismo , Streptomyces/enzimologia , Streptomyces/genética , Amidoidrolases/genética , Antifúngicos/química , Proteínas de Bactérias/genética , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/química , Genoma Bacteriano , Genômica , Estrutura Molecular , Família Multigênica , Fases de Leitura Aberta , Polienos/química , Streptomyces/metabolismo , Ésteres do Ácido Sulfúrico/químicaRESUMO
The mesenchymal have heterogeneous composition and till date no single, definitive marker for their identification is available. Further, this cell population is identified by their adherence to plastic, spindle-like morphology and their trilineage plasticity. They also have ability to differentiate into bone, cartilage and fat. Moreover, MSC as "multipotent stromal cells" is a preferred choice over "mesenchymal stem cells", as the later definition includes many cell populations, several of which do not fulfill the self-renewal and multi-lineage potential of true stem cells. So, the present review article is focused to enlighten recent views of MSC therapy in the field of Pediatrics.
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Diferenciação Celular/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Adesão Celular , Autorrenovação Celular/fisiologia , Criança , HumanosRESUMO
OBJECTIVES: To analyze the transcriptome of Spodoptera frugiperda 9 (Sf9) cells infected with AcMNPV or AcMNPV-BmK IT. RESULTS: A comprehensive transcriptome profile for Sf9 cells infected with AcMNPV or AcMNPV-BmK IT is shown. 43127572, 46529744 and 47235310 RNA-Seq profiles permitted the quantification of expression levels for control (C), AcMNPV-BmK IT treatment (ABT) and AcMNPV treatment (AT) groups. There were 997 up-regulated or down-regulated candidate genes with significant different expression level in these treatment groups. CONCLUSION: These results provide a broad spectrum of candidate genes that are critically involved in the molecular regulation mechanism of Sf9 cells infected with AcMNPV-BmK IT.
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Baculoviridae/genética , Genes de Insetos/genética , Células Sf9/metabolismo , Células Sf9/virologia , Transcriptoma/genética , Animais , Perfilação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/fisiologia , Nucleopoliedrovírus/genética , Venenos de Escorpião/genética , Venenos de Escorpião/metabolismo , Venenos de Escorpião/farmacologia , Células Sf9/imunologia , Transcriptoma/efeitos dos fármacosRESUMO
PURPOSE: H102, a novel ß-sheet breaker peptide, was encapsulated into liposomes to reduce its degradation and increase its brain penetration through intranasal administration for the treatment of Alzheimer's disease (AD). METHODS: The H102 liposomes were prepared using a modified thin film hydration method, and their transport characteristics were tested on Calu-3 cell monolayers. The pharmacokinetics in rats' blood and brains were also investigated. Behavioral experiments were performed to evaluate the improvements on AD rats' spatial memory impairment. The neuroprotective effects were tested by detecting acetylcholinesterase (AchE), choline acetyltransferase (ChAT) and insulin degrading enzyme (IDE) activity and conducting histological assays. The safety was evaluated on rats' nasal mucosa and cilia. RESULTS: The liposomes prepared could penetrate Calu-3 cell monolayers consistently. After intranasal administration, H102 could be effectively delivered to the brain, and the AUC of H102 liposomes in the hippocampus was 2.92-fold larger than that of solution group. H102 liposomes could excellently ameliorate spatial memory impairment of AD model rats, increase the activities of ChAT and IDE and inhibit plaque deposition, even in a lower dosage compared with H102 intranasal solution. H102 nasal formulations showed no toxicity on nasal mucosa. CONCLUSIONS: The H102-loaded liposome prepared in this study for nasal administration is stable, effective and safe, which has great potential for AD treatment.
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Doença de Alzheimer/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Peptídeos/administração & dosagem , Peptídeos/uso terapêutico , Acetilcolinesterase/metabolismo , Administração Intranasal , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Sequência de Aminoácidos , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Linhagem Celular , Colina O-Acetiltransferase/metabolismo , Lipossomos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Fármacos Neuroprotetores/farmacocinética , Peptídeos/farmacocinética , Ratos , Ratos Sprague-Dawley , Memória Espacial/efeitos dos fármacosRESUMO
Background: The efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain metastases in non-small cell lung cancer patients remains to be determined. Methods: A systematic search was conducted using databases including PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI), aiming to identify relevant clinical studies on the treatment of brain metastases originating from non-small cell lung cancer through the combination of EGFR-TKI and WBRT. Statistical analysis was performed utilizing Stata 17.0 software, covering clinical studies published until March 1, 2023. Results: This analysis incorporated 23 randomized controlled trials (RCTs), involving a total of 2,025 patients. Of these, 1,011 were allocated to the group receiving both EGFR-TKI and WBRT, while 1,014 were assigned to the WBRT alone group. The findings reveal that the combination of EGFR-TKI and WBRT significantly improves the intracranial objective remission rate (RR = 1.57, 95% CI: 1.42-1.74, p < 0.001), increases the intracranial disease control rate (RR = 1.30, 95% CI: 1.23-1.37, p < 0.001), and enhances the 1-year survival rate (RR = 1.48, 95% CI: 1.26-1.73, p < 0.001). Additionally, this combined treatment was associated with a significant survival advantage (RR = 1.48, 95% CI: 1.26-1.73, p < 0.001) and a reduced incidence of adverse effects (RR = 0.65, 95% CI: 0.51-0.83, p < 0.001), particularly with respect to nausea and vomiting (RR = 0.54, 95% CI: 0.37-0.81, p = 0.002) and myelosuppression (RR = 0.59, 95% CI: 0.40-0.87, p = 0.008). However, no statistically significant differences were observed for diarrhea (RR = 1.15, 95% CI: 0.82-1.62, p = 0.418), and skin rash (RR = 1.35, 95% CI: 0.88-2.07, p = 0.164). Conclusion: In contrast to WBRT alone, the combination of EGFR-TKI and WBRT significantly improves intracranial response, enhancing the objective response rate, disease control rate, and 1-year survival rate in NSCLC patients with brain metastases. Moreover, aside from mild cases of rash and diarrhea, there is no statistically significant increase in the incidence of additional adverse effects. Based on the comprehensive evidence collected, the use of third-generation EGFR-TKI combined with WBRT is recommended as the preferred treatment for NSCLC patients with brain metastases, offering superior management of metastatic brain lesions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#, CRD42023415566.
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BACKGROUND: Robotic Roux-en-Y gastric bypass (RRYGB) and conventional laparoscopic Roux-en-Y gastric bypass (LRYGB) are commonly performed as primary bariatric procedures. The aim of this article was to assess the role of RRYGB in patients undergoing primary bariatric procedures. METHODS: All of the qualified studies were selected from the PubMed, Embase, and Web of Science databases, etc. We mainly compared the outcomes and safety between RRYGB and LRYGB. The outcomes evaluation included surgical effect and surgical safety. RESULT: In total, 35 studies containing 426,463 patients were selected. The mortalities of patients adopting these 2 bariatric procedures were similar (RRYGB: 59/28,023, 0.21%; LRYGB: 612/397,945, 0.15%). We found no significant difference between RRYGB and LRYGB in the incidence of postoperative complications (30-day: OR=1.06, P =0.18; 1-y: OR=1.06, P =0.92). The incidence of 30-day readmission after the operation was higher in RRYGB patients (OR=1.24, P =0.003). However, we found that the RRYGB group had a lower incidence of anastomotic stricture 1 year after the operation when compared with LRYGB (OR=0.35, P =0.0004). The 1-year %EBMIL of these 2 groups was similar (78.53% vs. 76.02%). There was no significant difference in length of hospital stay (LOS) (WMD=-0.03d, P =0.59), conversion rate (OR=0.84, P =0.75), or anastomotic leak (OR=1.00, P =0.99) between these 2 groups. The mean hospital charges were higher in the RRYGB group ($11234.75 vs. $9468.58). CONCLUSION: This systematic review and meta-analysis showed no significant advantage of RRYGB in surgical effect or reduction of intraoperative complications. RRYGB may reduce the incidence of some postoperative long-term complications. The mean hospital charges of RRYGB were higher.
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Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Humanos , Derivação Gástrica/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Obesidade Mórbida/cirurgia , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Tempo de Internação/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Duração da Cirurgia , FemininoRESUMO
Objective: This study is aim to discern the Traditional Chinese Medicine (TCM) syndrome classifications relevant to immunotherapy sensitive in non-small cell lung cancer (NSCLC) patients, and to delineate intestinal microbiota biomarkers and impact that wield influence over the efficacy of NSCLC immunotherapy, grounded in the TCM theory of "lung and large intestine stand in exterior-interior relationship." Methods: The study cohort consisted of patients with advanced NSCLC who received treatment at the Oncology Department of Chengdu Fifth People's Hospital. These patients were categorized into distinct TCM syndrome types and subsequently administered immune checkpoint inhibitors (ICIs), specifically PD-1 inhibitors. Stool specimens were collected from patients both prior to and following treatment. To scrutinize the differences in microbial gene sequences and species of the intestinal microbiota, 16S rRNA amplicon sequencing technology was employed. Additionally, peripheral blood samples were collected, and the analysis encompassed the assessment of T lymphocyte subsets and myeloid suppressor cell subsets via flow cytometry. Subsequently, alterations in the immune microenvironment pre- and post-treatment were thoroughly analyzed. Results: The predominant clinical manifestations of advanced NSCLC patients encompassed spleen-lung Qi deficiency syndrome and Qi-Yin deficiency syndrome. Notably, the latter exhibited enhanced responsiveness to ICIs with a discernible amelioration of the immune microenvironment. Following ICIs treatment, significant variations in microbial abundance were identified among the three strains: Clostridia, Lachnospiraceae, and Lachnospirales, with a mutual dependency relationship. In the subset of patients manifesting positive PD-L1 expression and enduring therapeutic benefits, the study recorded marked increases in the ratios of CD3+%, CD4+%, and CD4+/CD8+ within the T lymphocyte subsets. Conversely, reductions were observed in the ratios of CD8%, Treg/CD4+, M-MDSC/MDSC, and G-MDSC/MDSC. Conclusion: The strains Clostridia, Lachnospiraceae, and Lachnospirales emerge as potential biomarkers denoting the composition of the intestinal microbiota in the NSCLC therapy. The immunotherapy efficacy of ICIs markedly accentuates in patients displaying durable treatment benefits and those expressing positive PD-L1.
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Carcinoma Pulmonar de Células não Pequenas , Microbioma Gastrointestinal , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Antígeno B7-H1 , RNA Ribossômico 16S/genética , Imunoterapia , Receptor de Morte Celular Programada 1 , Pulmão , Microambiente TumoralRESUMO
Beta-thalassemia is a potentially lethal hereditary anemia, caused by reduced or absent expression of HBB polypeptide chains of adult hemoglobin (HbA: α2ß2). Current curative treatments options are limited to few patients, while alternative, chronic palliative therapy consisting of frequent transfusions coupled with iron chelation therapy, are costly. The above treatments also affect quality of life of patients. A search was conducted in the electronic databases like Medline, PubMed, etc. for screening studies reporting various aspects including gene therapy, prevention strategies, blood, transfusion and chelation therapy for the management of ß-thalassemia. Increased levels of fetal hemoglobin (HbF: α2γ2) were shown to lessen the severity of ß-thalassemia, highlighting the therapeutic potential of a gene-therapy-mediated increase in HBG1 and HBG2 (HBG) expression. The primary outcome of most of the above studies was the efficient management of ß-thalassemia, without any major complication. So, the present review is focused on the recent perspectives in the management of ß-thalassemia including combinatorial gene therapy for ß-thalassemia.
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Talassemia beta , Adulto , Terapia por Quelação , Criança , Hemoglobina Fetal/genética , Hemoglobina Fetal/metabolismo , Hemoglobina A , Humanos , Qualidade de Vida , Talassemia beta/diagnóstico , Talassemia beta/genética , Talassemia beta/terapiaRESUMO
[This corrects the article DOI: 10.3892/ol.2017.6106.].
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At present, it is a considerable challenge to mimic the complex architecture of osteochondral (OC) tissue. In this study, a porous and gradient mineralized double-network hydrogel is synthesized and used to induce bone marrow mesenchymal stem cells (BMSCs) to differentiate into the desired OC tissue depending only on the material and mechanical properties. Physical and chemical characterizations show that hydroxyapatite nanoparticles grow and fill into the pores of the hydrogel, and their content presents a gradient change in different layers of hydrogel. The synthesized hydrogel has excellent mechanical properties and the compression strength with different mineralization degrees varies from 27 to 380 kPa, which fully meets the needs of increased mechanical strength of articular cartilage from the surface to the deep layer. Besides, the synthesized hydrogel has good biocompatibility that can promote the proliferation and growth of BMSCs. More importantly, the results of histochemistry, immunohistochemistry, and real time polymerase chain reaction show that gradient mineralized hydrogel can induce BMSCs to differentiate into the desired chondrocytes and osteoblasts in different layers of hydrogels, indicating that OC tissues can be successfully constructed through a simple induction differentiation of gradient mineralized hydrogel.
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Regeneração Óssea/efeitos dos fármacos , Cartilagem Articular/patologia , Diferenciação Celular/efeitos dos fármacos , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/citologia , Animais , Condrogênese/efeitos dos fármacos , Técnicas de Cocultura , Colágeno Tipo I/metabolismo , Colágeno Tipo II/metabolismo , Fibrinogênio/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Porosidade , Proteoglicanas/metabolismo , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
Osteosarcoma is the most common primary malignant bone tumor type in children and adolescents under 20 years of age. Biological characteristics include invasiveness, metastasis, abnormal differentiation and loss of contact inhibition. microRNAs (miRNAs) are involved in the transcriptional and post-transcriptional regulation of target mRNAs. Previous studies have demonstrated that miR-218 inhibits tumor formation and progression in glioma, colon cancer and renal cell carcinoma; however, the mechanism of action of miR-218 in osteosarcoma has not been completely determined. In the present study, it was demonstrated that miR-218 exhibited low expression and targeted E2F2 in osteosarcoma cells. Additionally, overexpression of miR-218 inhibited osteosarcoma cell proliferation, with the opposite result occurring following the knockdown of miR-218. Furthermore, it was determined that miR-218 inhibited tumor formation and reduced the expression of E2F2 and proliferating cell nuclear antigen in nude mice. Collectively, the present data demonstrated that miR-218 serves an important role in suppressing the proliferation of osteosarcoma cells, potentially regulated by E2F2, which may provide a novel protein marker for the treatment of osteosarcoma.
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RATIONALE: Childhood chronic myeloid leukemia (CCML) is a malignant disease of granulocyte abnormal hyperplasia that is caused by clonal proliferation of pluripotent stem cells. The condition is relatively rare, accounting for 2.0% to 3.0% of cases of childhood leukemia. In addition, the incidence of extramedullary blast crisis in CCML presenting as central nervous system (CNS) blast crisis remaining chronic phase of the disease in bone marrow is extremely unusual. PATIENT CONCERNS: We report a case of childhood chronic myelogenous leukemia that abandoned treatment, resulting in chronic myelogenous leukemia transforming into extramedullary blast crisis resulting in CNS leukemia, accompanied by the chronic phase of the disease in bone marrow. DIAGNOSES: Chronic myeloid leukemia extramedullary blast crisis presenting as CNS leukemia without blast crisis in bone marrow. INTERVENTIONS: Following high-dose systemic and intrathecal chemotherapy, the patient continued to do well. LESSONS: High-dose systemic and intrathecal chemotherapy is safe and helpful for CCML extramedullary blast crisis. A long-term follow-up is crucial.
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Antineoplásicos/uso terapêutico , Crise Blástica/diagnóstico , Neoplasias do Sistema Nervoso Central/patologia , Crise Blástica/complicações , Crise Blástica/tratamento farmacológico , Medula Óssea/patologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Survival after acute paediatric (0-14 years), adolescent (15-19 years) and young adult (20-39 years) leukaemia has improved substantially over the last five decades, particularly for acute lymphoblastic leukaemia (ALL) and acute promyelocytic leukaemia. This progress represents one of the most successful achievements in the history of medicine and has been attributed to the development of effective chemotherapy regimens, improvement in supportive care, better risk stratification, use of targeted therapies, and advances in haematopoietic stem cell transplantation. Recent studies have revealed improvement in survival over time for all age groups and subtypes of leukaemia. However, these outcomes varied widely by age and are associated with sociodemographic and clinical factors. The present review concludes that survival and early death after acute leukaemia has greatly improved among young patients. However, inequalities in outcomes remain and are likely a result of multiple factors.
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OBJECTIVE: To investigate the effect of ß-sheet breaker peptide H102 on APP associated secretase in the hippocampus brain regions of APP/PS1 double transgenic mice(AD mice). METHODS: Thirty 6-month-old APP/PS1 double transgenic mice were randomly divided into AD group and H102 group, a group of C57BL/6J mice with the same age, number and background was set as controls(n=15). H102 (5.8 mg/kg) 5 µl was infused by intranasal administration to mice in H102 treatment group, and equal volume of blank solution of H102 was given to mice in control group and AD group. The ability of spatial reference memory was tested by Morris water maze after 30 days of treatment. And then immunohistochemistry tests and Western blot were used to detect the content of α-secretase (ADAM10, ADAM17), ß-secretase (BACE1), γ-secretase (PS1, APH1a, PEN2) in the hippocampus brain regions. RESULTS: Compared with the control group, the expression of BACE1, PS1, PEN-2 and APH1-a protein in the hippocampus of AD group were significantly increased, ADAM10, ADAM17 protein expression were significantly reduced (P<0.05); Compared with the model group, H102 could significantly improve the spatial learning and memory ability of AD mice, significantly decreased the expression of BACE1, PS1, PEN-2 and APH1-a protein in the hippocampus, significantly increased the expression of ADAM10 and ADAM17 protein(P<0.05). CONCLUSIONS: ß sheet peptides blocked H102 can reduce the formation of Aß in the hippocampus brain area, improve the activity of α-secretase in the hippocampus brain region, decrease the activity of ß-and γ-secretase, improve the learning and memory ability of AD mice.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/efeitos dos fármacos , Hipocampo/enzimologia , Memória/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Proteína ADAM10/metabolismo , Proteína ADAM17/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Modelos Animais de Doenças , Endopeptidases/metabolismo , Hipocampo/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-1/metabolismo , Conformação Proteica em Folha betaRESUMO
OBJECTIVE: To explore the single nucleotide polymorphism(SNP) of mitochondrial DNA (mtDNA) D-LOOP region in peripheral blood lymphocytes of immuno-related pancytopenia (IRP) patients and its correlation with immune parameters. METHODS: The D-LOOP region in mitochondrial DNA of lymphocytes in peripheral blood mononuclear cells from 43 patients with untreated IRP was detected by polymerase chain reaction(PCR). The PCR products were sequenced by the pros and cons direct sequencing methods. The sequencing results were compared with the revised Cambridge reference sequence (rCRS) and the Polymorphic Sites of Human Mitochondrial Genome Database. RESULTS: Among total of 110 variant positions of D-LOOP region in 43 patients, 62 was SNP sites and 48 was mutation sites, of which 14 were the new mutation sites not yet registered in the database, 516 base variations were observed at 110 positions, the most common variations were base substitutions, among them T/C and A/G was 184/410 and 113/410 respectively. In the 110 variant positions, the high frequency variation sites were 73 and 263 for 43/43,311 for 32/43,310 and 16 224 for 27/43,16 519 for 25/43, 489 and 16 362 for 24/43. By the analysis of mitochondrial DNA D-LOOP polymorphism and related clinical immunology indicators of the patient's lymphocytes, it was found that D-loop in adult patients (age≥ 18 years old) significantly correlated with CD15 IgM, GLYCoA+ Cells IgM, CD34+ CellsIgG, CD34+ Cells IgM correlation. CONCLUSION: The high frequency of polymorphism exists in mitochondrial DNA D-loop region of lymphocytes in IRPA patients, and was significantly correlates with the autoantibodies in bone marrow mononuclear cells in adult patients, which may be associated with the IRP occurrence.