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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(7): 701-707, 2024 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-39014946

RESUMO

OBJECTIVES: To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence. METHODS: A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed. RESULTS: Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group (P>0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage (n=62, 42.5%) and the early stage (n=46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene (HR=4.177, 95%CI: 2.086-8.364, P<0.001) and minimal residual disease≥0.01% on day 46 (HR=2.013, 95%CI: 1.163-3.483, P=0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol. CONCLUSIONS: There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Feminino , Fatores de Risco , Pré-Escolar , Estudos Retrospectivos , Lactente , Recidiva , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , População do Leste Asiático
2.
Sci Adv ; 9(44): eadh1582, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37910617

RESUMO

Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti-programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors.


Assuntos
Neoplasias da Coroide , Melanoma , Animais , Camundongos , Corpo Vítreo , Vitrectomia , Hidrogéis , Recidiva Local de Neoplasia/patologia , Melanoma/patologia , Neoplasias da Coroide/cirurgia , Neoplasias da Coroide/patologia , Melfalan , Imunoterapia
3.
Adv Sci (Weinh) ; 10(25): e2302747, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37379237

RESUMO

Retinal degeneration, characterized by the progressive loss of retinal neurons, is the leading cause of incurable visual impairment. Retinal progenitor cells (RPCs)-based transplantation can facilitate sight restoration, but the clinical efficacy of this process is compromised by the imprecise neurogenic differentiation of RPCs and undermining function of transplanted cells surrounded by severely oxidative retinal lesions. Here, it is shown that ultrathin niobium carbide (Nb2 C) MXene enables performance enhancement of RPCs for retinal regeneration. Nb2 C MXene with moderate photothermal effect markedly improves retinal neuronal differentiation of RPCs by activating intracellular signaling, in addition to the highly effective RPC protection by scavenging free radicals concurrently, which has been solidly evidenced by the comprehensive biomedical assessments and theoretical calculations. A dramatically increased neuronal differentiation is observed upon subretinal transplantation of MXene-assisted RPCs into the typical retinal degeneration 10 (rd10) mice, thereby contributing to the efficient restoration of retinal architecture and visual function. The dual-intrinsic function of MXene synergistically aids RPC transplantation, which represents an intriguing paradigm in vision-restoration research filed, and will broaden the multifunctionality horizon of nanomedicine.


Assuntos
Degeneração Retiniana , Camundongos , Animais , Degeneração Retiniana/terapia , Retina , Células-Tronco , Transplante de Células
4.
Cell Tissue Res ; 392(3): 689-704, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36802303

RESUMO

Retinal degenerative diseases such as glaucoma, retinitis pigmentosa, and age-related macular degeneration pose serious threats to human visual health due to lack of effective therapeutic approaches. In recent years, the transplantation of retinal progenitor cells (RPCs) has shown increasing promise in the treatment of these diseases; however, the application of RPC transplantation is limited by both their poor proliferation and their differentiation capabilities. Previous studies have shown that microRNAs (miRNA) act as essential mediators in the fate determination of stem/progenitor cells. In this study, we hypothesized that miR-124-3p plays a regulatory role in the fate of RPC determination by targeting Septin10 (SEPT10) in vitro. We observed that the overexpression of miR124-3p downregulates SEPT10 expression in RPCs, leading to reduced RPC proliferation and increased differentiation, specifically towards both neurons and ganglion cells. Conversely, antisense knockdown of miR-124-3p was shown to boost SEPT10 expression, enhance RPC proliferation, and attenuate differentiation. Moreover, overexpression of SEPT10 rescued miR-124-3p-caused proliferation deficiency while weakening the enhancement of miR-124-3p-induced-RPC differentiation. Results from this study show that miR-124-3p regulates RPC proliferation and differentiation by targeting SEPT10. Furthermore, our findings enable a more comprehensive understanding into the mechanisms of proliferation and differentiation of RPC fate determination. Ultimately, this study may be useful for helping researchers and clinicians to develop more promising and effective approaches to optimize the use of RPCs in treating retinal degeneration diseases.


Assuntos
MicroRNAs , Degeneração Retiniana , Humanos , Proliferação de Células/genética , Células Cultivadas , Células-Tronco , Diferenciação Celular/genética , MicroRNAs/genética , MicroRNAs/metabolismo
5.
Sci Adv ; 9(4): eabq3104, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36706184

RESUMO

Therapeutic antibodies are extensively used to treat fundus diseases by intravitreal injection, as eyedrop formulation has been rather challenging due to the presence of ocular barriers. Here, an innovative penetrating carrier was developed for antibody delivery in eyedrop formulations. We found that fluorocarbon-modified chitosan (FCS) would self-assemble with proteins to form nanocomplexes, which could effectively pass across the complicated ocular structure to reach the posterior eye segments in both mice and rabbits. In a choroidal melanoma-bearing mouse model, eyedrops containing FCS/anti-PDL1 could induce stronger antitumor immune responses than those triggered by intravenous injection of anti-PDL1. Moreover, in choroidal neovascularization-bearing mouse and rabbit models, FCS/anti-VEGFA eyedrops effectively inhibited vascular proliferation, achieving comparable therapeutic responses to those observed with intravitreal injection of anti-VEGFA. Our work presents an effective delivery carrier to treat fundus diseases using eyedrop of therapeutic proteins, which may enable at-home treatment of many eye diseases with great patient compliance.


Assuntos
Neovascularização de Coroide , Coelhos , Animais , Camundongos , Soluções Oftálmicas , Fundo de Olho , Modelos Animais de Doenças , Neovascularização de Coroide/tratamento farmacológico
6.
Adv Mater ; 35(2): e2204994, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36349821

RESUMO

Age-related macular degeneration (AMD) is a major cause of visual impairment and severe vision loss worldwide, while the currently available treatments are often unsatisfactory. Previous studies have demonstrated both inflammation and oxidative-stress-induced damage to the retinal pigment epithelium are involved in the pathogenesis of aberrant development of blood vessels in wet AMD (wet-AMD). Although antivascular endothelial growth factor (VEGF) therapy (e.g., Ranibizumab) can impair the growth of new blood vessels, side effects are still found with repeated monthly intravitreal injections. Here, an injectable antibody-loaded supramolecular nanofiber hydrogel is fabricated by simply mixing betamethasone phosphate (BetP), a clinic anti-inflammatory drug, anti-VEGF, the gold-standard anti-VEGF drug for AMD treatment, with CaCl2 . Upon intravitreal injection, such BetP-based hydrogel (BetP-Gel), while enabling long-term sustained release of anti-VEGF to inhibit vascular proliferation in the retina and attenuate choroidal neovascularization, can also scavenge reactive oxygen species to reduce local inflammation. Remarkably, such BetP-Gel can dramatically prolong the effective treatment time of conventional anti-VEGF therapy. Notably, anti-VEGF-loaded supramolecular hydrogel based on all clinically approved agents may be readily translated into clinical use for AMD treatment, with the potential to replace the current anti-VEGF therapy.


Assuntos
Nanofibras , Degeneração Macular Exsudativa , Humanos , Inibidores da Angiogênese/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Hidrogéis/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico
7.
Front Immunol ; 13: 936707, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958546

RESUMO

Background: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune inflammatory disorder characterized by bilateral granulomatous uveitis. The objective of this study was to identify immune hub genes involved in the pathogenesis and progression of VKH disease. Methods: High throughput sequencing data were downloaded from the Gene Expression Omnibus (GEO) and an immune dataset was downloaded from ImmPort. Immune differentially expressed genes (DEGs) were obtained from their intersection in the GEO and ImmPort datasets. Immune hub genes for VKH disease were selected through differential expression analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), protein-protein interaction (PPI) network, and clustering analyses. Confidence in the immune hub genes was subsequently validated using box plots and receiver operating characteristic (ROC) curves. Results: A total of 254 DEGs were screened and after the intersection with ImmPort, 20 genes were obtained as immune DEGs. Functional enrichment analysis indicated that the key genes were mainly involved in several types of immune pathways (such as the lymphocyte mediated and leukocyte mediated immune responses, natural killer cell mediated cytotoxicity, and antigen binding) and immunodeficiency diseases. Following PPI network analysis, the top seven genes in cluster 1 were selected as potential immune hub genes in VKH. After evaluating the accuracy of the hub genes, one gene (GNLY) was excluded because its expression level was statistically similar in VKH patients and healthy controls. Finally, six immune hub genes, namely KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2 were identified as playing important roles in the occurrence and development of VKH disease. Conclusion: Six immune hub genes (KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2) identified by our bioinformatics analyses may provide new diagnostic and therapeutic targets for VKH disease.


Assuntos
Síndrome Uveomeningoencefálica , Análise por Conglomerados , Biologia Computacional , Ontologia Genética , Humanos , Subfamília C de Receptores Semelhantes a Lectina de Células NK , Mapas de Interação de Proteínas/genética , Síndrome Uveomeningoencefálica/genética
8.
Medicine (Baltimore) ; 101(49): e32228, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36626449

RESUMO

BACKGROUND: This study aimed to systematically analyze the association between long-term use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC). METHODS: We performed a systematic search of articles on the relationship between long-term use of PPIs and the risk of GC from PubMed and EMBASE. We calculated the pooled odds ratio of GC in PPI users compared to non-PPI users using random-effects models. RESULTS: This meta-analysis included 18 studies from 20 different databases with 4348,905 patients enrolled. In the random effects model, we found that an increased risk of GC among PPI users (OR = 1.94; 95% CI [1.43, 2.64]). The long-term use of PPIs compared with histamine-2 receptor antagonist users did not increase the risk of GC (OR = 1.65; 95% CI [0.92, 2.97]). Stratified analysis showed that PPI users had a significantly increased risk of noncardia GC (OR = 2.53; 95% CI [2.03, 3.15]), but had a relatively small relationship with the risk of gastric cardia cancer. (OR = 1.79; 95% CI [1.06, 3.03]). With the extension of PPI use time, the estimated risk value decreases (<1 year: OR = 6.33, 95% CI [3.76, 10.65]; 1-3 years: OR = 1.82, 95% CI [1.30, 2.55]; >3 years: OR = 1.25, 95% CI [1.00, 1.56]). Despite Helicobacter pylori eradication, the long-term use of PPIs did not alter the increased risk of GC (OR = 2.29; 95% CI [1.57, 3.33]). CONCLUSION: Our meta-analysis found that PPI use may be associated with an increased risk of GC. Further research on the causal relationship between these factors is necessary.


Assuntos
Inibidores da Bomba de Prótons , Neoplasias Gástricas , Humanos , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/epidemiologia
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 835-840, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511174

RESUMO

OBJECTIVES: To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria. METHODS: A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group (n=28) and myeloid expression group (n=11). The clinical features, treatment, and prognosis were compared between the two groups. RESULTS: The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% (P<0.05). The children with negative minimal residual disease (MRD) after induction therapy had a significantly higher 3-year EFS rate than those with positive MRD (96%±4% vs 38%±28%, P<0.05). Positive ETV6-RUNX1 was observed in the myeloid expression group, and positive BCR-ABL1, positive MLL-r, and hyperleukocytosis (white blood cell count ≥50×109/L) were observed in the ALAL group. There was no significant difference in the 3-year EFS rate between the myeloid expression and ALAL groups (100%±0% vs 66%±11%, P>0.05). CONCLUSIONS: ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Criança , Intervalo Livre de Doença , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
10.
Zhongguo Zhong Yao Za Zhi ; 46(2): 406-411, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645129

RESUMO

The aim of this paper was to discuss the effect of swertiamarin, gentiopicrin and sweroside on rheumatoid arthritis fibroblast-like synoviocytes(RA-FLSs) and B-cell lymphoma-2(Bcl-2) and their mechanisms. ZINC database and RCSB PDB database were retrieved for 3 D chemical structures of swertiamarin, gentiopicrin and sweroside and 3 D target protein structures. AutoDock Mgltools 1.5.6, AutoDockVina 1.1.2 and pyMOL 2.2.0 were applied for molecular docking to analyze the relationship between Bcl-2(1 GJH) target protein and important ingredients. The cell apoptosis of RA-FLSs was tested by Annexin V-FITC. The Bcl-2 protein expression of RA-FLSs treated with different ingredients was tested by Western blot. The Bcl-2 mRNA expression of RA-FLSs treated with different ingredients was tested by RT-PCR. Swertiamarin, gentiopicrin and sweroside were docked well with Bcl-2(1 GJH). The binding energy of swertiamarin was-6.9 kcal·mol~(-1), the binding energy of gentiopicrin was-6.7 kcal·mol~(-1) and the binding energy of sweroside was-6.4 kcal·mol~(-1). Compared with the blank group, the Bcl-2 protein expression of each group were reduced, while that of the gentiopicrin group was the highest(P<0.01). Compared with the blank group, the Bcl-2 mRNA expression of each groups were reduced. Gentiopicrin can reduce the Bcl-2 protein expression and the Bcl-2 mRNA expression, so as to promote the RA-FLSs apoptosis.


Assuntos
Artrite Reumatoide , Sinoviócitos , Apoptose , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Proliferação de Células , Células Cultivadas , Fibroblastos , Humanos , Glucosídeos Iridoides , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-bcl-2/genética , Pironas
11.
Bioact Mater ; 6(4): 990-997, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33102941

RESUMO

Retinal degeneration is a main class of ocular diseases. So far, retinal progenitor cell (RPC) transplantation has been the most potential therapy for it, in which promoting RPCs neuronal differentiation remains an unmet challenge. To address this issue, innovatively designed L/ d - phenylalanine based chiral nanofibers (LPG and DPG) are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation. qPCR, western blot, and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation, whereas left-handed LPG nanofibers decrease this effect. These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4 (RBP4, a key protein in the retinoic acid (RA) metabolic pathway). The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers.

12.
Gastroenterol Hepatol ; 44(4): 286-292, 2021 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33097281

RESUMO

BACKGROUND AND AIMS: The regular arrangement of collecting venules (RAC) refers to the appearance of multiple regular tiny veins in the body of the stomach and is considered to be very effective for identifying gastric mucosa with non-Helicobacter pylori infection. This meta-analysis was conducted to systematically evaluate the value of the sign in predicting a Helicobacter pylori-negative stomach and the relevant factors that may affect the performance of this prediction. METHODS: Two biomedical databases (PubMed and EMBASE) were systematically searched through April 20, 2020. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the SROC curve (AUC) were calculated. RESULTS: Fourteen articles with 4070 patients were included. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC for the RAC in predicting non-Hp infection were 0.80 (0.67-0.89), 0.97 (0.93-0.98), 24.8 (12.2-50.8), 0.21 (0.12-0.36), 120 (47-301) and 0.97 (0.19-1.00), respectively. CONCLUSIONS: The RAC is a valuable endoscopic feature for the prediction of patients without Hp infection.


Assuntos
Gastroscopia , Estômago/irrigação sanguínea , Estômago/patologia , Vênulas , Helicobacter pylori , Humanos , Valor Preditivo dos Testes
13.
Cell Death Differ ; 28(1): 283-302, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32814879

RESUMO

Adipose-derived mesenchymal stem cells (ADSCs) are promising candidate for regenerative medicine to repair non-healing bone defects due to their high and easy availability. However, the limited osteogenic differentiation potential greatly hinders the clinical application of ADSCs in bone repair. Accumulating evidences demonstrate that circular RNAs (circRNAs) are involved in stem/progenitor cell fate determination, but their specific role in stem/progenitor cell osteogenesis, remains mostly undescribed. Here, we show that circRNA-vgll3 originating from the vgll3 locus markedly enhances osteogenic differentiation of ADSCs; nevertheless, silencing of circRNA-vgll3 dramatically attenuates ADSC osteogenesis. Furthermore, we validate that circRNA-vgll3 functions in ADSC osteogenesis through a circRNA-vgll3/miR-326-5p/integrin α5 (Itga5) pathway. Itga5 promotes ADSC osteogenic differentiation and miR-326-5p suppresses Itga5 translation. CircRNA-vgll3 directly sequesters miR-326-5p in the cytoplasm and inhibits its activity to promote osteogenic differentiation. Moreover, the therapeutic potential of circRNA-vgll3-modified ADSCs with calcium phosphate cement (CPC) scaffolds was systematically evaluated in a critical-sized defect model in rats. Our results demonstrate that circRNA-vgll3 markedly enhances new bone formation with upregulated bone mineral density, bone volume/tissue volume, trabeculae number, and increased new bone generation. This study reveals the important role of circRNA-vgll3 during new bone biogenesis. Thus, circRNA-vgll3 engineered ADSCs may be effective potential therapeutic targets for bone regenerative medicine.


Assuntos
Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Osteogênese/genética , RNA Circular/metabolismo , Fatores de Transcrição/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Diferenciação Celular/genética , Células Cultivadas , Integrina alfa5/metabolismo , Masculino , MicroRNAs/genética , RNA Circular/genética , RNA-Seq , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/genética
14.
Epigenomics ; 12(12): 1027-1040, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32657141

RESUMO

Aims: To profile and characterize the circular RNA (circRNA) expression pattern in poorly differentiated gastric adenocarcinoma (PDGA). Methods & materials: CircRNA expression profiles in PDGA and adjacent nontumor tissues were analyzed by microarray. Five randomly selected differentiated expressed circRNAs (DECs) were validated by real-time quantitative PCR. m6A qualification of the top 20 DECs was conducted by m6A-immunoprecipitation and real-time quantitative PCR. Results: A total of 65 DECs were found in PDGA compared with the control. Hsa_circRNA_0077837 had the largest area under the curve. Most DECs had m6A modifications, the trend of m6A modification alteration was mainly consistent with the circRNA expression level. Conclusion: Our study revealed a set of DECs and their m6A modification alterations, which may provide new insight for their potential function in PDGA.


Assuntos
Adenocarcinoma/genética , Metilação de DNA , RNA Circular/genética , Neoplasias Gástricas/genética , Adenosina , Idoso , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
15.
Cell Cycle ; 19(14): 1754-1767, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32544377

RESUMO

Retinal degenerations, which lead to irreversible decline in visual function, are still no effective recovery treatments. Currently, retinal progenitor cell (RPC) transplantation therapy is expected to provide a new approach to treat these diseases; however, the limited proliferation capacity and differentiation potential toward specific retinal neurons of RPCs hinder their potential clinical applications. microRNAs have been reported to serve as important regulators in the cell fate determination of stem/progenitor cells. In this study, our data demonstrated that miR-762 inhibited NPDC1 expression to positively regulate RPC proliferation and suppress RPC neuronal differentiation. Furthermore, the knockdown of miR-762 upregulated NPDC1 expression in RPCs, leading to the inhibition of RPC proliferation and the increase in neuronal differentiation. Moreover, NPDC1 could rescue anti-miR-762-induced RPC proliferation deficiency and the inhibitory effect of miR-762 on RPC differentiation. In conclusion, our study demonstrated that miR-762 plays a crucial role in regulating RPC proliferation and differentiation by directly targeting NPDC1, which is firstly reported that microRNAs positively regulate RPC proliferation and negatively regulate RPC differentiation, which provides a comprehensive understanding of the molecular mechanisms that dominate RPC proliferation and differentiation in vitro.


Assuntos
MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Retina/citologia , Animais , Sequência de Bases , Diferenciação Celular/genética , Proliferação de Células/genética , Células Cultivadas , Regulação da Expressão Gênica , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , Modelos Biológicos , Proteínas do Tecido Nervoso/genética
16.
ACS Appl Mater Interfaces ; 12(25): 27889-27904, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32130854

RESUMO

Large-sized orbital bone defects have serious consequences that destroy orbital integrity and result in maxillofacial deformities and vision loss. The treatment of orbital bone defects is currently palliative and not reparative, suggesting an urgent demand for biomaterials that regenerate orbital bones. In this study, via alloying, extrusion and surface modification, we developed mechanobiologically optimized magnesium (Mg) scaffolds (Ca-P-coated Mg-Zn-Gd scaffolds, referred to as Ca-P-Mg) for the orthotopic reconstruction of large-sized orbital bone defects. At 6 months after transplanting the scaffolds to a clinically relevant canine large animal model, large-sized defects were successfully bridged by an abundance of new bone with normal mechanical properties that corresponded to gradual degradation of the implants. The osteogenic and ancillary cells, including vascular endothelial cells and trigeminal neurons, played important roles in this process. The scaffolds robustly enhanced bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation. In addition, the increased angiogenesis including increased ratio of the specific endothelial subtype CD31hi endomucinhi (CD31hiEmcnhi) endothelial cells can facilitate osteogenesis. Furthermore, the scaffolds trigger trigeminal neurons via transient receptor potential vanilloid subtype 1 (Trpv1) to produce the neuropeptide calcitonin gene-related peptide (CGRP), which promotes angiogenesis and osteogenesis. Overall, our investigations revealed the efficacy of Ca-P-Mg scaffolds in healing orbital bone defects and warrant further exploration of these scaffolds for clinical applications.


Assuntos
Magnésio/química , Células-Tronco Mesenquimais/citologia , Alicerces Teciduais/química , Animais , Regeneração Óssea/fisiologia , Diferenciação Celular/fisiologia , Cães , Osteogênese/genética , Osteogênese/fisiologia
17.
Expert Rev Gastroenterol Hepatol ; 14(3): 207-220, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32063071

RESUMO

Objectives: This study aimed to compare the efficacy of various anti-ulcer medications in preventing delayed bleeding and promoting ulcer healing after ESD.Methods: Asystematic search was conducted for articles up to August2019. The treatments of iatrogenic ulcer were analyzed by Bayesian network meta-analysis.Results: The analysis included 28 studies. Six treatments were compared. For the prevention of delayed bleeding, potassium-competitive acid blocker (P-CAB) alone was superior to proton-pump inhibitor (PPI) alone [RR = 1.02, 95%CI (1.00, 1.05)]. Treatments based on P-CAB tended to be better than the non-P-CAB groups [RR = 1.05, 95%CI (1.03, 1.07)]. Concerning the ulcer healing rate at 4 weeks, the combined treatment of PPI and mucoprotective agent (MP) was superior to PPI alone [RR = 1.81, 95%CI (1.19, 2.76)] and P-CAB alone [RR = 2.75, 95%CI (1.02, 7.44)]. At 8 weeks, PPI+MP and P-CAB+MP tend to be superior to than the other four groups. The healing effect of MP-based therapies was better than that of non-MP groups at 4 weeks [RR = 1.63, 95%CI (1.32, 2.01)] and 8 weeks [RR = 1.06, 95%CI (1.02, 1.11)].Conclusion: P-CAB may prevent delayed bleeding, but not significantly. MP agents have the potential to heal post-ESD ulcers.


Assuntos
Antiulcerosos/uso terapêutico , Ressecção Endoscópica de Mucosa/efeitos adversos , Gastroscopia/efeitos adversos , Neoplasias Gástricas/cirurgia , Úlcera Gástrica/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Metanálise em Rede , Úlcera Gástrica/etiologia , Resultado do Tratamento , Cicatrização/efeitos dos fármacos
18.
Gastroenterol Res Pract ; 2019: 1953497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31871444

RESUMO

BACKGROUND: Helicobacter pylori is an important carcinogenic factor in gastric cancer. Studies have shown that Helicobacter pylori infection is inversely associated with certain diseases such as esophageal cancer and whose infection appears to have a "protective effect." At present, the relationship between Helicobacter pylori infection and esophageal cancer remains controversial. This study was designed to investigate the relationship between Helicobacter pylori infection and the risk of esophageal cancer in different regions and ethnicities. METHODS: Systematic search of the articles on the relationship between Helicobacter pylori infection and esophageal cancer from the database with the duration time up to December 2018. This systematic review was performed under the MOOSE guidelines. RESULTS: This meta-analysis included 35 studies with 345,886 patients enrolled. There was no significant correlation between Helicobacter pylori infection and esophageal squamous cell carcinoma in the general population (OR: 0.84; 95% CI: 0.64-1.09/OR: 0.74; 95% CI: 0.54-0.97). However, a significant correlation was found in the Middle East (OR: 0.34; 95% CI: 0.22-0.52/95% CI: 0.26-0.44). There was no significant difference in the prevalence of Helicobacter pylori between the case group and the control group in esophageal adenocarcinoma (8.87% vs. 9.67%). The pooled OR was 0.55 (95% CI: 0.43-0.70) or 0.23 (95% CI: 0.15-0.36). When grouped by match or not, the pooled OR of the nonmatching group and the matching group was 0.48/0.21 (95% CI: 0.36-0.65/95% CI: 0.13-0.36) and 0.73/0.71 (95% CI: 0.57-0.92/95% CI: 0.60-0.84), respectively. CONCLUSION: In the general populations, no significant association was found between Helicobacter pylori infection and the risk of esophageal squamous cell carcinoma. However, lower risk was found in the Middle East. Helicobacter pylori infection may reduce the risk of esophageal adenocarcinoma, but such "protection effect" may be overestimated.

19.
Med Sci Monit ; 25: 7439-7442, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31582716

RESUMO

BACKGROUND This study aimed to identify the risk factors of complications after small-intestinal polypectomy by single-balloon enteroscopy (SBE), and to assess the value of serum C-reactive protein (CRP) and the max polyp diameter (Dmax) in predicting postoperative complications of small-intestinal polypectomy. MATERIAL AND METHODS Between April 2017 and April 2018, clinical data from 37 patients who underwent small-intestinal polypectomy were retrospectively analyzed. RESULTS Thirty-seven small-intestinal polypectomy procedures (18 oral and 19 anal) were carried out in 37 patients (M: F 20: 17; age 35.6±13.0 years). A total of 1081 small-intestine polyps were removed. Three patients (8.1%) had bleeding and 3 patients (8.1%) had perforation after small-intestinal polypectomy. Based on multivariate logistic analysis, CRP [1.104 (95% CI 1.022-1.191)] was the only risk factor for complications among the patients. According to the area under the receiver operating characteristic (AUROC) curve, CRP (27.5 mg/L), Dmax (3.5 cm), and the combination of CRP + Dmax appear to be predictive factors for complications after small-intestinal polypectomy. CONCLUSIONS SBE is an effective endoscopic tool for patients with small-intestinal polyps. CRP, Dmax, and the combination of CRP+Dmax may be potential predictors of complications from small-intestinal polypectomy.


Assuntos
Pólipos Intestinais/cirurgia , Enteroscopia de Balão Único/métodos , Adulto , Área Sob a Curva , Biomarcadores/sangue , Biópsia , Proteína C-Reativa/análise , China , Pólipos do Colo/cirurgia , Colonoscopia/métodos , Feminino , Hemorragia/complicações , Humanos , Pólipos Intestinais/complicações , Intestino Delgado/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Enteroscopia de Balão Único/efeitos adversos , Enteroscopia de Balão Único/mortalidade
20.
Biomater Sci ; 7(6): 2335-2347, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-30907911

RESUMO

Retinal progenitor cell (RPC)-based transportation therapy is a promising strategy for repairing visual loss caused by retinal degeneration (RD) in people; however, its application is still significantly limited by the low effective delivery, proliferation and differentiation of RPCs. Herein, a self-healing injectable hydrogel (CS-Odex) based on chitosan hydrochloride (CS) and oxidized dextran (Odex) was developed via a dynamic Schiff-base linkage as a bioactive vehicle for the delivery of RPCs. Moreover, its biological effects on the RPC behaviors, including survival, proliferation and differentiation, were systematically evaluated. The CS-Odex hydrogel exhibits good biocompatibility and suitable mechanical stiffness for the growth of RPCs, and the cells can retain a high survival ratio (about 90%) with the protection of the self-healing CS-Odex hydrogels post-injection. In addition, the proliferation of RPCs in the CS-Odex hydrogels was significantly enhanced by activating the Akt and Erk pathways, especially in the hydrogel with higher CS content. Moreover, the differentiation of RPCs was improved by the CS-Odex hydrogel. Particularly, the differentiation of RPCs towards photoreceptors, the most important cell-type for RD, was elevated. Therefore, the self-healing injectable CS-Odex hydrogel would provide a promising platform for the delivery of RPCs and promote the proliferation and differentiation of RPCs towards RPC-based transplantation therapy in the future.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Fenômenos Mecânicos , Retina/citologia , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Quitosana/química , Dextranos/química , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hidrogéis/administração & dosagem , Injeções , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/metabolismo , Bases de Schiff/química
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