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1.
Autoimmun Rev ; : 103578, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39004157

RESUMO

Efferocytosis is a crucial process whereby phagocytes engulf and eliminate apoptotic cells (ACs). This intricate process can be categorized into four steps: (1) ACs release "find me" signals to attract phagocytes, (2) phagocytosis is directed by "eat me" signals emitted by ACs, (3) phagocytes engulf and internalize ACs, and (4) degradation of ACs occurs. Maintaining immune homeostasis heavily relies on the efficient clearance of ACs, which eliminates self-antigens and facilitates the generation of anti-inflammatory and immunosuppressive signals that maintain immune tolerance. However, any disruptions occurring at any of the efferocytosis steps during apoptosis can lead to a diminished efficacy in removing apoptotic cells. Factors contributing to this inefficiency encompass dysregulation in the release and recognition of "find me" or "eat me" signals, defects in phagocyte surface receptors, bridging molecules, and other signaling pathways. The inadequate clearance of ACs can result in their rupture and subsequent release of self-antigens, thereby promoting immune responses and precipitating the onset of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. A comprehensive understanding of the efferocytosis process and its implications can provide valuable insights for developing novel therapeutic strategies that target this process to prevent or treat autoimmune diseases.

2.
Oncol Rep ; 42(6): 2245-2254, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31578585

RESUMO

Platinum­containing doublet chemotherapy is the cornerstone of lung cancer treatment; however, cisplatin resistance is a major obstacle in the treatment of lung cancer. However, the mechanism underlying this resistance has not been fully elucidated. Previous studies have shown that serum apurinic/apyrimidinic endonuclease 1 (APE1) levels in patients with NSCLC are inversely associated with progression­free survival after platinum­containing doublet chemotherapy, and can serve as a biomarker for predicting disease prognosis and treatment efficacy. The present study was designed to investigate the role played by APE1 in the resistance of lung cancer to cisplatin. The levels of mitochondrial apurinic endonuclease 1 (m­APE1) and total APE1 (t­APE1) protein in a cisplatin­resistant A549 cell line (A549/DDP) and cisplatin­sensitive A549 cells were analyzed by western blotting. Mitochondrial membrane potential was detected by using the JC­1 staining method. The cisplatin­resistance of APE1­overexpressing A549 cells and APE1­silenced A549/DDP cells was assessed by cell apoptosis and colony formation assays. The results revealed that cisplatin­resistant A549 cells contained high levels of APE1, and exhibited elevated levels of autophagy. The levels of m­APE1 and t­APE1 protein were increased in the A549/DDP cells when compared with these levels in the A549 cells. Overexpression of APE1 and Mia40 enhanced the cisplatin resistance and autophagy of the A549 cells. APE1 knockdown restored the cisplatin sensitivity and reduced the levels of LC3II and Parkin in the A549/DDP cells, but promoted the release of cytochrome c. Furthermore, Parkin silencing or treatment with 3­methyladenine (3­MA, an autophagy inhibitor) promoted the apoptosis of APE1­overexpressing A549 cells, indicating that Parkin­mediated mitophagy plays an important role in the APE1­induced cisplatin resistance of A549 cells. In conclusion, APE1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin­mediated mitophagy.


Assuntos
Autofagia , Cisplatino/farmacologia , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/patologia , Mitofagia , Ubiquitina-Proteína Ligases/metabolismo , Células A549 , Antineoplásicos/farmacologia , Apoptose , Proliferação de Células , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Potencial da Membrana Mitocondrial , Células Tumorais Cultivadas , Ubiquitina-Proteína Ligases/genética
3.
Inorg Chem ; 56(17): 10281-10289, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28809503

RESUMO

High-density materials have attracted extensive attention because of their broad applications. However, strategies for improving the densities of MOFs and preparing denser MOFs remain almost unexplored. Herein, we propose a tandem anion-ligand exchange strategy for synthesizing denser MOFs by using three-dimensional cationic MOFs (3D CMOFs) with pillared layered structures as precursors and high-density anions and small monotopic ligands as exogenous guests. By means of this strategy, we choose the high-density nitroformate ion [C(NO2)3-] as an exogenous anion and water as an exogenous ligand to successfully synthesize two layered CMOFs. Single-crystal X-ray diffraction showed that after this transformation, the extra-framework anions are replaced with the C(NO2)3- anions, and the distances between adjacent layers in the two-dimensional (2D) networks are more than 3.70 Å shorter than those of their 3D precursors. The resultant materials exhibit higher densities, higher heats of detonation, higher nitrogen and oxygen contents, and lower metal contents. In particular, the density of {Cu(atrz)2[C(NO2)3]2(H2O)2·atrz·2H2O}n (2b, ρ = 1.76 g cm-3, atrz = 4,4'-azo-1,2,4-triazole) is increased by 0.12 g cm-3 compared to its 3D precursor {2a, [Cu(atrz)3(NO3)2·2H2O]n, ρ = 1.64 g cm-3}, and its heat of detonation is also enhanced to more than 1900 kJ kg-1. The resultant 2D layered CMOFs are also new potential high-energy density materials. This work may provide new insights into the design and synthesis of high-density MOFs. Moreover, we anticipate that the approach reported here would be useful for the preparation of new MOFs, in particular, which are otherwise difficult or unfeasible through traditional synthetic routes.

4.
Molecules ; 22(7)2017 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-28672873

RESUMO

High-energy metal-organic frameworks (MOFs) based on nitrogen-rich ligands are an emerging class of explosives, and density is one of the positive factors that can influence the performance of energetic materials. Thus, it is important to design and synthesize high-density energetic MOFs. In the present work, hydrothermal reactions of Cu(II) with the rigid polynitro heterocyclic ligands 5,5'-dinitro-2H,2'H-3,3'-bi-1,2,4-triazole (DNBT) and 5,5'-dinitro-3,3'-bis-1,2,4-triazole-1-diol (DNBTO) gave two high-density MOFs: [Cu(DNBT)(ATRZ)3]n (1) and [Cu(DNBTO)(ATRZ)2(H2O)2]n (2), where ATRZ represents 4,4'-azo-1,2,4-triazole. The structures were characterized by infrared spectroscopy, elemental analysis, ultraviolet-visible (UV) absorption spectroscopy and single-crystal X-ray diffraction. Their thermal stabilities were also determined by thermogravimetric/differential scanning calorimetry analysis (TG/DSC). The results revealed that complex 1 has a two-dimensional porous framework that possesses the most stable chair conformations (like cyclohexane), whereas complex 2 has a one-dimensional polymeric structure. Compared with previously reported MOFs based on copper ions, the complexes have higher density (ρ = 1.93 g cm-3 for complex 1 and ρ = 1.96 g cm-3 for complex 2) and high thermal stability (decomposition temperatures of 323 °C for complex 1 and 333.3 °C for complex 2), especially because of the introduction of an N-O bond in complex 2. We anticipate that these two complexes would be potential high-energy density materials.


Assuntos
Cobre/química , Substâncias Explosivas/síntese química , Estruturas Metalorgânicas/síntese química , Triazóis/síntese química , Varredura Diferencial de Calorimetria , Cristalografia por Raios X , Substâncias Explosivas/química , Estruturas Metalorgânicas/química , Modelos Moleculares , Estrutura Molecular , Teoria Quântica , Espectrometria de Fluorescência , Triazóis/química , Difração de Raios X
5.
Int J Clin Exp Pathol ; 10(11): 11030-11036, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31966448

RESUMO

Transforming growth factor-ß (TGF-ß) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-ß family expressed in a variety of human carcinoma cell lines. Although accumulating evidence has shown that BMP9 plays important roles in the regulation of various cellular processes, the function of BMP9 in clinical osteosarcoma remains to be explored. In this study, BMP9 expression was analyzed in 55 osteosarcoma patient samples and their matching, distant non-cancerous tissues. And the roles of BMP9 in osteosarcoma cell proliferation, apoptosis and cell cycle were also examined. Our results showed that different expression level of BMP9 was detected in all osteosarcoma samples while no expression in normal tissues. Surprisingly, there was a negative association between the expression level of BMP9 and osteosarcoma grade, with low level of BMP9 being found in high histological grade osteosarcoma. Knockdown of BMP9 accelerated the proliferation of MG63, SaOS-2, and U2OS cells. BMP9 overexpression, however, induced cell apoptosis in U2OS cells. Together, these results indicated that BMP9 plays a pivotal role in osteosarcoma. Future studies defining the mechanism of BMP9 effect may lead to novel therapeutic approaches for osteosarcoma.

6.
Oncotarget ; 7(19): 27975-87, 2016 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-27057625

RESUMO

Accumulating evidence suggests that the tumor suppressor gene Krüppel-like factor 6 (KLF6) plays important roles in both development and progression of cancer. However, the role of KLF6 in hepatocellular carcinoma (HCC) remains unclear. Cancer-related molecule basigin-2 plays an important role in HCC progression and metastasis. Sp1, one of Sp/KLFs family members, regulates basigin-2 expression in HCC. The involvement of KLFs in basigin-2 regulation and HCC progression and metastasis has not been investigated. We first measured KLF6 expression levels in 50 pairs of HCC and adjacent normal tissues (ANTs) by immunohistochemistry. Specifically, low KLF6 expression but high Sp1 and basigin-2 expression were found in HCC tissues. By contrast, the ANTs showed high KLF6 expression but low Sp1 and basigin-2 expression. Kaplan-Meier analysis showed that higher expression of KLF6 was associated with better overall survival. The survival rate of KLF6-negative patients was lower than that of KLF6-positive patients (P = 0.015). We also found that KLF6 binds to the basigin-2 and Sp1 promoters and decreases their expression. Thus, we identified a microcircuitry mechanism in which KLF6 can repress basigin-2 expression directly by binding to its promoter or indirectly by inhibiting the expression of the transcription factor Sp1 to block gene expression. Additionally, overexpression of KLF6 suppressed the invasion, metastasis and proliferation of HCC cells in vitro and in vivo by targeting basigin-2. Our study provides new evidence that interaction of KLF6 and Sp1 regulates basigin-2 expression in HCC and that KLF6 represses the invasive and metastatic capacities of HCC through basigin-2.


Assuntos
Basigina/biossíntese , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Fator 6 Semelhante a Kruppel/metabolismo , Neoplasias Hepáticas/patologia , Fator de Transcrição Sp1/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Proliferação de Células/fisiologia , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/patologia
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