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1.
J Colloid Interface Sci ; 606(Pt 1): 898-911, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34481249

RESUMO

Developing photocatalysts that are inexpensive and efficient in degrading pollutants are essential for environmental remediation. Herein, a novel system of perylene diimide (PDI)/CuS p-n heterojunction was synthesized by a two-step self-assembly strategy for removal of tetracycline in waste water. Results showed that PDI/CuS-10% exhibited highest photocatalytic behavior. The apparent rate constants for tetracycline (TC) degradation for the blend were 5.27 and 2.68 times higher than that of CuS or PDI, respectively. The enhancement of photocatalytic activity was mainly attributed to the π-π stacking and p-n junction, which can accelerate the separation of the photo-generated h+-e- pairs. Besides, the light absorption of PDI/CuS from 800 to 200 nm was significantly enhanced and the absorption edge even reached the near-infrared region, which also played an important role in providing desired photocatalytic properties. Surprisingly, PDI/CuS could maintain high catalytic activity even after 5 cycles under simulated conditions, indicating that the composite had high potential for practical applications. Owing to high efficiency, low cost and wide application range, the PDI/CuS nanocomposites are promising candidates for environmental remediation.

2.
Environ Pollut ; 287: 117671, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34435562

RESUMO

In humans and animal models, the kidneys and cardiovascular systems are negatively affected by BPA from the environment. It is considered that BPA have some potential estrogen-like and non-hormone-like properties. In this study, RNA-sequencing and its-related bioinformatics was used as the basic strategy to clarify the characteristic mechanisms of kidney-heart axis remodeling and dysfunction in diabetic male rats under BPA exposure. We found that continuous BPA exposure in diabetic rats aggravated renal impairment, and caused hemodynamic disorders and dysfunctions. There were 655 and 125 differentially expressed genes in the kidney and heart, respectively. For the kidneys, functional annotation and enrichment, and gene set enrichment analyses identified bile acid secretion related to lipid synthesis and transport, and MAPK cascade pathways. For the heart, these bioinformatics analyses clearly pointed to MAPKs pathways. A total of 12 genes and another total of 6 genes were identified from the kidney tissue and heart tissue, respectively. Western blotting showed that exposure to BPA activated MAPK cascades in both organs. In this study, the exacerbated remodeling of diabetic kidney-heart axis under BPA exposure and diabetes might occur through hemodynamics, metabolism disorders, and the immune-inflammatory response, as well as continuous estrogen-like stimulation, with focus on the MAPK cascades.


Assuntos
Diabetes Mellitus Experimental , Transcriptoma , Animais , Compostos Benzidrílicos , Biologia Computacional , Rim , Masculino , Fenóis , Ratos
3.
Cancer Sci ; 112(9): 3585-3597, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34252986

RESUMO

Diffuse large B cell lymphoma (DLBCL) heterogeneity promotes recurrence and anti-CD20-based therapeutic resistance. Previous studies have shown that downregulation of MS4A1/CD20 expression after chemoimmunotherapy with rituximab leads to rituximab resistance. However, the mechanisms of CD20 loss remain unknown. We identified that pyruvate dehydrogenase kinase 4 (PDK4) is markedly elevated in DLBCL cells derived from both patients and cell lines with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) resistance. We found that overexpression of PDK4 in DLBCL cells resulted in cell proliferation and resistance to rituximab in vitro and in vivo. Furthermore, loss of PDK4 expression or treatment with the PDK4 inhibitor dichloroacetate was able to significantly increase rituximab-induced cell apoptosis in DLBCL cells. Further studies suggested PDK4 mediates a metabolic shift, in that the main energy source was changed from oxidative phosphorylation to glycolysis, and the metabolic changes could play an important role in rituximab resistance. Importantly, by knocking down or overexpressing PDK4 in DLBCL cells, we showed that PDK4 has a negative regulation effect on MS4A1/CD20 expression. Collectively, this is the first study showing that targeting PDK4 has the potential to overcome rituximab resistance in DLBCL.


Assuntos
Antígenos CD20/metabolismo , Antineoplásicos Imunológicos/administração & dosagem , Reprogramação Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Glicoproteínas/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Rituximab/administração & dosagem , Transdução de Sinais/genética , Adolescente , Adulto , Idoso , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Transfecção , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
4.
J Nanobiotechnology ; 19(1): 179, 2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34120620

RESUMO

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is a malignant disease of lymphoid tissue. At present, chemotherapy is still the main method for the treatment of NHL. R-CHOP can significantly improve the survival rate of patients. Unfortunately, DOX is the main cytotoxic drug in R-CHOP and it can lead to adverse reactions. Therefore, it is particularly important to uncover new treatment options for NHL. RESULTS: In this study, a novel anti-tumor nanoparticle complex Nm@MSNs-DOX/SM was designed and constructed in this study. Mesoporous silica nanoparticles (MSNs) loaded with Doxorubicin (DOX) and anti-inflammatory drugs Shanzhiside methylester (SM) were used as the core of nanoparticles. Neutrophil membrane (Nm) can be coated with multiple nanonuclei as a shell. DOX combined with SM can enhance the anti-tumor effect, and induce apoptosis of lymphoma cells and inhibit the expression of inflammatory factors related to tumorigenesis depending on the regulation of Bcl-2 family-mediated mitochondrial pathways, such as TNF-α and IL-1ß. Consequently, the tumor microenvironment (TME) was reshaped, and the anti-tumor effect of DOX was amplified. Besides, Nm has good biocompatibility and can enhance the EPR effect of Nm@MSNs-DOX/SM and increase the effect of active targeting tumors. CONCLUSIONS: This suggests that the Nm-modified drug delivery system Nm@MSNs-DOX/SM is a promising targeted chemotherapy and anti-inflammatory therapy nanocomplex, and may be employed as a specific and efficient anti-Lymphoma therapy.

5.
ACS Appl Mater Interfaces ; 13(24): 27920-27933, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34125517

RESUMO

Chemotherapy is one of the main treatment methods for osteosarcoma. However, conventional chemotherapy lacks targeting properties, and its long-term and extensive use will have serious side effects on patients. For this reason, a multifunctional nanodrug system (V-RZCD) targeting osteosarcoma was developed in this study. V-RZCD consists of two parts: (1) the core (ZCD), wherein calcium ions (Ca2+) and zoledronic acid (ZA) form a metal-organic framework for loading doxorubicin (DOX), and (2) the shell (V-R), a vascular endothelial growth factor (VEGF) ligand-modified red blood cell membrane nanovesicle. By targeting the VEGF, V-RZCD can specifically bind to the VEGF receptors that are highly expressed on the surface of osteosarcoma cells. Importantly, compared with free ZA and DOX, V-RZCD not only clearly inhibits the proliferation of osteosarcoma but also significantly inhibits osteolysis induced by osteosarcoma. In summary, V-RZCD represents a new way to treat osteosarcoma.


Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Estruturas Metalorgânicas/química , Osteólise/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Animais , Antineoplásicos/química , Neoplasias Ósseas/tratamento farmacológico , Cálcio/química , Linhagem Celular Tumoral , Doxorrubicina/química , Liberação Controlada de Fármacos , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteólise/etiologia , Osteossarcoma/complicações , Osteossarcoma/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ácido Zoledrônico/química
6.
ACS Appl Mater Interfaces ; 13(26): 30434-30457, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34161080

RESUMO

In the face of the abundant production of various types of carbapenemases, the antibacterial efficiency of imipenem, seen as "the last line of defense", is weakening. Following, the incidence of carbapenem-resistant Acinetobacter baumannii (CRAB), which can generate antibiotic-resistant biofilms, is increasing. Based on the superior antimicrobial activity of silver nanoparticles against multifarious bacterial strains compared with common antibiotics, we constructed the IPM@AgNPs-PEG-NOTA nanocomposite (silver nanoparticles were coated with SH-PEG-NOTA as well as loaded by imipenem) whose core was a silver nanoparticle to address the current challenge, and IPM@AgNPs-PEG-NOTA was able to function as a novel smart pH-sensitive nanodrug system. Synergistic bactericidal effects of silver nanoparticles and imipenem as well as drug-resistance reversal via protection of the ß-ring of carbapenem due to AgNPs-PEG-NOTA were observed; thus, this nanocomposite confers multiple advantages for efficient antibacterial activity. Additionally, IPM@AgNPs-PEG-NOTA not only offers immune regulation and accelerates tissue repair to improve therapeutic efficacy in vivo but also can prevent the interaction of pathogens and hosts. Compared with free imipenem or silver nanoparticles, this platform significantly enhanced antibacterial efficiency while increasing reactive oxygen species (ROS) production and membrane damage, as well as affecting cell wall formation and metabolic pathways. According to the results of crystal violet staining, LIVE/DEAD backlight bacterial viability staining, and real-time quantitative polymerase chain reaction (RT-qPCR), this silver nanocomposite downregulated the levels of ompA expression to prevent formation of biofilms. In summary, this research demonstrated that the IPM@AgNPs-PEG-NOTA nanocomposite is a promising antibacterial agent of security, pH sensitivity, and high efficiency in reversing resistance and synergistically combatting carbapenem-resistant A. baumannii. In the future, various embellishments and selected loads for silver nanoparticles will be the focus of research in the domains of medicine and nanotechnology.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Portadores de Fármacos/química , Nanocompostos/uso terapêutico , Prata/uso terapêutico , Acinetobacter baumannii/fisiologia , Animais , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Feminino , Compostos Heterocíclicos com 1 Anel/química , Imipenem/química , Imipenem/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Nanocompostos/química , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/metabolismo , Prata/química , Resistência beta-Lactâmica/efeitos dos fármacos
7.
J Nanobiotechnology ; 19(1): 8, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407527

RESUMO

BACKGROUND: Non-Hodgkin's lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibody targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Therefore, we constructed a low pH value sensitivity drug delivery system based on the cancer cell membrane modified mesoporous silica nanoparticles loaded with traditional Chinese medicine, which can reduce systemic toxicity and improve the therapeutic effect for the targeted drug delivery of tumor cells. RESULTS: Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, low pH value sensitivity, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis. CONCLUSIONS: Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma.


Assuntos
Antineoplásicos/administração & dosagem , Membrana Celular , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Linfoma/tratamento farmacológico , Nanopartículas/química , Animais , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis , Proliferação de Células , Modelos Animais de Doenças , Furocumarinas/farmacologia , Humanos , Medicina Tradicional Chinesa , Camundongos Nus , Espécies Reativas de Oxigênio , Dióxido de Silício
8.
Mater Sci Eng C Mater Biol Appl ; 119: 111648, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33321684

RESUMO

Lymphoma is a well-known malignant tumor in the human body. Although many anticancer drugs have been developed to improve the survival rate of patients, about 40% of patients continue to be recurrent or refractory, a key issue needing remedy. Therefore, it is necessary to identify alternative treatments to reduce the disease's mortality. To this effect, a new type of anti-lymphoma nanocomplex FA@RBCm-AgNPs was prepared using AgNPs as the core of nanoparticles along with the targeting molecule folic acid inserted erythrocyte membrane as the shell. The biomimetic properties of red blood cell membrane (RBCm) endow F-RAN with good biocompatibility as well as the ability to evade clearance of the reticuloendothelial system. In addition, F-RAN was modified with folic acid to actively and selectively identify tumor cells. In vivo and in vitro experiments demonstrate that F-RAN can inhibit lymphoma cells and induce apoptosis of stem cells while promoting apoptosis of lymphoma with no obvious side effects. Hence, F-RAN may serve as a new treatment for lymphoma.


Assuntos
Linfoma , Nanopartículas Metálicas , Nanopartículas , Apoptose , Biomimética , Linhagem Celular Tumoral , Humanos , Linfoma/tratamento farmacológico , Prata
9.
ACS Omega ; 5(34): 21468-21475, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32905387

RESUMO

Cotton-based catalytic fabric (CCF) was prepared by the simple padding-drying method with the copolymer of five functional monomers as the modifier and was applied in the solid-liquid-liquid phase-transfer catalysis (SLL-PTC) system. Effects of the structure of the function monomer, the content of the cation, and the loading amount on the catalytic activity of CCF were investigated. The lipophilicity, disperse extent of cationic center, and the accessory to the ion for CCF were influenced by the structure and content of the function monomer. The organic phase was adsorbed on the surface of the catalytic fabric, and the novel catalytic cycle in the PTC system was initiated. The anion in the aqueous phase diffuses through the interfacial region to the site for ion exchange. Bond-forming reaction was initiated in the interfacial region between the organic phase on the fabric and the aqueous phase. The conversion rate for Williamson ether synthesis reaction reached 92%, and CCF could be reused five times in this SLL-PTC system.

10.
Front Chem ; 8: 565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32766207

RESUMO

Jolkinolide B (JB) is a bioactive compound isolated from a Chinese herbal medicine that exerts antitumor activity. However, the anti-lymphoma effect of JB and its mechanism are yet to be revealed. Because free JB has poor pharmacokinetics and weak antitumor efficacy, we opted to use black phosphorus quantum dot (BPQD) nanomaterials as a drug loading platform to synthesize a nano-traditional Chinese medicine (nano-TCM) called BPQDs@JB. Compared with free JB, Raji cells administrated with BPQDs@JB exhibited the cell viability of 19.85 ± 1.02%, and the production of intracellular reactive oxygen species (ROS) was promoted. Likewise, BPQDs@JB was capable of rising the apoptosis rate of Raji cells to 34.98 ± 1.76%. In nude mice transplanted tumor model administrated with BPQDs@JB, the tumor tissue sections administrated with BPQDS@JB achieved a conspicuous red fluorescence, demonstrating the presence of most ROS production in the BPQDS@JB. TUNEL achieved a number of positive (brown) nuclei in vivo, revealing that BPQDS@JB could significantly induce tumor tissue apoptosis. As revealed from the mentioned results, BPQDs@JB can generate considerable ROS and interfere with the redox state to inhibit tumor. In brief, BPQDs@JB may be adopted as a treatment option for lymphoma.

11.
Huan Jing Ke Xue ; 41(3): 1265-1275, 2020 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608628

RESUMO

To explore the water purification efficiency and phytoplankton control efficiency of the water source ecological purification system, and evaluate the effectiveness of the functional group (FG) and morphology-based functional group (MBFG) in response to the internal environment and water quality of the water source ecological purification system, in the summer of 2018, the water quality and phytoplankton functional groups of each unit of the Yanlong Lake ecological purification system were monitored and analyzed. The results showed that the Yanlong Lake water source ecological purification system can effectively purify the water. The average values of total phosphorus, total nitrogen, dissolved oxygen, and turbidity in the influent water were 0.20 mg·L-1, 1.91 mg·L-1, 2.88 mg·L-1, and 60.23 NTU, respectively; after system treatment, these were 0.09 mg·L-1, 0.95 mg·L-1, 6.26 mg·L-1, and 39.53 NTU, respectively. Simultaneously, the spatial distribution of water quality within the system was heterogeneous, with significant spatial differences in dissolved oxygen (DO), pH, and turbidity (P<0.001). The Yanlong Lake water source ecological purification system could effectively control the density of phytoplankton (4.42×105-4.32×106 cells·L-1) when the effluent was in a mild eutrophication state. This reduced the risk of algal blooms. There were five absolute advantage FG:B, P, TC, J, and W1. There were six absolute advantage MBFG:GroupⅠ, GroupⅢ, GroupⅣ, GroupⅤ, GroupⅥ, and GroupⅦ. Both absolute dominant functional groups were effective in indicating changes in habitat conditions. The results of RDA analysis found that the environmental interpretation of the MBFG was higher than that of the FG. The results suggested that it is more appropriate to study the dynamics of phytoplankton in the Yanlong Lake ecological purification system in summer by selecting the MBFG classification method.

12.
Front Chem ; 8: 377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32457875

RESUMO

Zirconia nanoparticles (ZrO2 NPs) are widely applied in the field of biomedicine. In this study, we constructed a nanoplatform of ZrO2 NPs coated with a platelet membrane (PLTm), named PLT@ZrO2. PLTm nanovesicles camouflage ZrO2 NPs, prevent nanoparticles from being cleared by macrophage, and target tumor sites. Compared to ZrO2 alone, PLT@ZrO2 is better at inhibiting the invasion and metastasis of Hela cells in vitro and in vivo. In vitro, PLT@ZrO2 inhibited the growth and proliferation of Hela cells. Scratch-wound healing recovery assay demonstrated that PLT@ZrO2 inhibited Hela cells migration. Transwell migration and invasion assays showed that PLT@ZrO2 inhibited Hela cells migration and invasion. In vivo, PLT@ZrO2 inhibited the tumor growth of Xenograft mice and inhibited the lung and liver metastasis of Hela cells. Immunofluorescence and Western blotting results showed that anti-metastasis protein (E-cadherin) was upregulated and pro-metastasis proteins (N-cadherin, Smad4, Vimentin, E-cadherin,ß-catenin, Fibronectin, Snail, Slug, MMP2, Smad2) were down-regulated. Our study indicated that PLT@ZrO2 significantly inhibits tumor growth, invasion, and metastasis.

13.
Aging (Albany NY) ; 12(10): 9585-9603, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457254

RESUMO

OBJECTIVE: The cardiotoxicity of doxorubicin (DOX) reduces the quality of life and prognosis of cancer patients, and therefore its clinical application has been largely restricted. This study aimed to assess the effects of cryptotanshione (CPT) on DOX-induced rat cardiac insufficiency. RESULTS: CPT treatment significantly suppressed apoptosis in vitro. The oral administration of CPT significantly improved cardiac function in the rat model, reduced collagen production and suppressed apoptosis and the production of reactive oxygen species in the heart tissue. Transcriptomic profiling and its relevant bioinformatics analysis showed that CPT suppressed doxorubicin-induced cardiotoxicity by inhibiting p53 signaling pathway. CONCLUSION: Transcriptomic profiling and bioinformatics analysis can be used to evaluate the cardio-protective effect of CPT through inactivating p53 signaling pathway in the doxorubicin-mediated myocardial damage model. METHODS: F-actin staining and flow cytometry were used to assess the effects of CPT on cardiomyocytes. In vivo, echocardiography and hemodynamic evaluation were used to assess the effects of CPT on the cardiac dysfunction in rats. Furthermore, transcriptomic profiling and bioinformatics analysis, as well as western blot analysis, were used to determine that CPT induced changes in the signaling pathways in the model.


Assuntos
Cardiotônicos/farmacologia , Cardiopatias/tratamento farmacológico , Redes e Vias Metabólicas/genética , Fenantrenos/farmacologia , Transcriptoma/genética , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/genética , Biologia Computacional , Bases de Dados Genéticas , Modelos Animais de Doenças , Doxorrubicina , Perfilação da Expressão Gênica , Coração/efeitos dos fármacos , Cardiopatias/induzido quimicamente , Cardiopatias/genética , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
ACS Appl Mater Interfaces ; 12(20): 22687-22701, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32330381

RESUMO

Toxicity and drug resistance caused by chemotherapeutic drugs have become bottlenecks in treating tumors. The delivery of anticancer drugs based on nanocarriers is regarded as an ideal way to solve the aforementioned problems. In this study, a new antilymphoma nanodrug CD20 aptamer-RBCm@Ag-MOFs/PFK15 (A-RAMP) is designed and constructed, and it consists of two parts: (1) metal-organic frameworks Ag-MOFs (AM) loaded with tumor aerobic glycolysis inhibitor PFK15 (P), forming a core part (AMP); (2) targeted molecule CD20 aptamer (A) is inserted into the red blood cell membrane (RBCm) to form the shell part (A-R). A-RAMP under the guidance of CD20 aptamer actively targets B-cell lymphoma both in vitro and in vivo. As a result, A-RAMP not only significantly inhibits the effect on tumor growth but also shows no obvious side effects on the treated nude mice, indicating that A-RAMP can accurately target tumor cells, reprogram aerobic glycolysis, and exert synergistic antitumor effect by Ag+ and PFK 15. Furthermore, the antitumor mechanism of A-RAMP in vivo by apoptotic pathway and targeting metabonomics are explored. These results suggest that A-RAMP has a promising application prospect as an smart, safe, effective, and synergistic antilymphoma agent.


Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Glicólise/efeitos dos fármacos , Linfoma de Células B/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Nanocompostos/química , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Aptâmeros de Nucleotídeos/química , Sequência de Bases , Materiais Biomiméticos/química , Membrana Eritrocítica/química , Humanos , Células K562 , Estruturas Metalorgânicas/química , Camundongos , Camundongos Endogâmicos BALB C , Piridinas/uso terapêutico , Quinolinas/uso terapêutico , Células RAW 264.7 , Prata/química , Prata/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Onco Targets Ther ; 13: 473-486, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021291

RESUMO

Background: Isatin derivatives have extensive biological activities, such as antitumor. IF203, a novel isatin derivative, has not previously been reported to have antitumor activity. Methods: Acid phosphatase assays (APAs) and Ki-67 immunohistochemistry were used to detect the proliferation of HepG2 cells. Transmission electron microscope (TEM) was applied to detect ultrastructural changes. Flow cytometry (FCM) was used to detect cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of HepG2 cells in vitro. TUNEL, MMP and ROS immunofluorescence assays were applied to assess apoptosis, MMP, and ROS of HepG2 cells in vivo. Western Blotting was applied to assess the levels of apoptosis- and autophagy-related proteins. Results: In this study, in vivo and in vitro experiments showed that IF203 possesses antitumor activity. The results of APAs and Ki-67 immunohistochemistry demonstrated that IF203 could inhibit the proliferation of HepG2 cells. Cell cycle assays, downregulation of Cyclin B1 and Cdc2, and upregulation of P53 suggested that IF203 could lead to G2/M cell cycle arrest. In addition, ultrastructural changes, apoptosis assays, TUNEL immunofluorescence results, upregulated expression of Bax, and downregulated expression of Bcl-2 suggest that IF203 can induce apoptosis in HepG2 cells. After IF203 treatment, intracellular ROS levels increased, MMP decreased, JC-1 green fluorescence was enhanced, and the levels of Caspase-9, Caspase-3 and Cytochrome C expression were upregulated, suggesting that IF203 could induce apoptosis of HepG2 cells through the mitochondrial apoptosis pathway. Moreover, characteristic apoptotic ultrastructural changes were accompanied by the appearance of many autophagy bubbles and upregulation of Atg5, Atg12, ULK1, Beclin-1 and LC3-II proteins, suggesting that IF203 could induce autophagy in HepG2 cells. Conclusion: This study showed that IF203 leads to the death of HepG2 cells through cell cycle arrest, apoptotic induction, and autophagy promotion.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1476-1481, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607301

RESUMO

OBJECTIVE: To explore the mechanisms of angiogenesis in chronic myeloid leukemia (CML) through detecting the levels of angiogenesis-related factors secreted from K562 cells after overexpression and interference of HIF-1α gene in K562 cells. METHODS: The K562 cells were transfected by lentiviruses carried and interfered HIF-1α gene, then the transtected K562 cells with carried and interfered with HIF-1α gene were enrolled in overexpression and interference groups respectively, at the same time the K562 cells transfected by the empty virus were enrolled in control group. The cells were harvested after culture for 72 hours under normoxid condition. The transfection efficient in 3 groups was detected by fluorescence microscopy; the mRNA expression of HIF-1α gene and angiogenesis-related factors was detected by RT-PCR; the concentration of angiogenesis-related factors in the caltured supernatant was detected by ELISA. RESULTS: The optimal MOI of K562 cells transfected with lentivirus was 10 and the transfection efficiency was about 50%. The positive rate of transfection after screening by puromycin was more than 90%. The mRNA expression of ANG-I, ANG-II, TGF-α and VEGF in the interference group was lower than that in the over-expression group, and the TGF-ß1 mRNA expression in the interference group was higher than in the over-expression group. The mRNA expression of ANG-I and VEGF in the interference group was lower than that in the control group. TGF-αdid not could be detected, and the culture supernatant concentration of ANG-I and TNF-α in the interference group was lower than in the over-expression group, while the VEGF concentration in the interference group was higher than that in the over-expression group. All of the above-mentioned differences were statistically significant (P<0.05). CONCLUSION: The positive K562 cells transfected with leutivirus have been harvested by screening with puromycin. The HIF-1α mRNA positively regulates the mRNA expression of ANG-1, ANG-2, TGF-α, VEGF in K562 cells, promotes the antocrine ability of ANG-1 and TNF-α, moreover not stimulates the autocrine of TGF-α, the up-regulation of HIF-1α expression can inhibit the expression TGF-ß1 in K562 cells and the autocrine of TGF-ß1.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Humanos , Células K562 , RNA Mensageiro , Fator A de Crescimento do Endotélio Vascular
17.
ACS Appl Mater Interfaces ; 11(31): 28254-28266, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31291079

RESUMO

Hederagenin (HED) has poor anticancer activity whose mechanism remains unclear and unsystematic. Free drugs for cancer treatment exhibit disadvantages such as poor targeting and efficacy. To address this problem, we constructed a nanoplatform of black phosphorus quantum dots (BPQDs) camouflaged with a platelet membrane (PLTm) carrying HED, termed PLT@BPQDs-HED. PLTm vesicles serve as a shell to encapsulate multiple high-efficiency drug-loaded nanocores, which can target tumor sites and significantly improve antitumor activity. Compared with free HED, this platform significantly reduced tumor cell viability and the mitochondrial membrane potential (MMP), while increasing the production of intracellular reactive oxygen species (ROS). The platform also significantly increased the amounts of terminal deoxyribonucleotide transferase mediated dUTP nick-end-labeling (TUNEL)-positive cells and decreased the number of Ki-67-positive cells. In addition, the platform upregulated proapoptotic factor Bax, downregulated the anti-apoptotic molecule Bcl-2, activated Caspase-9 and Caspase-3, and stimulated Cytochrome C release. Moreover, the platform promoted the formation of autophagosomes, upregulated Beclin-1, and promoted LC3-I conversion into LC3-II. This study demonstrated that the above platform significantly enhances tumor targeting and promotes mitochondria-mediated cell apoptosis and autophagy in tumor cells.


Assuntos
Antineoplásicos , Apoptose/efeitos dos fármacos , Morte Celular Autofágica/efeitos dos fármacos , Plaquetas , Neoplasias da Mama/tratamento farmacológico , Membrana Celular , Fósforo , Pontos Quânticos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Células MCF-7 , Camundongos , Fósforo/química , Fósforo/farmacocinética , Fósforo/farmacologia , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Células RAW 264.7 , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Integr Plant Biol ; 61(2): 120-139, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30589221

RESUMO

Although the mechanism of DNA methylation-mediated gene silencing is extensively studied, relatively little is known about how promoter methylated genes are protected from transcriptional silencing. SUVH1, an Arabidopsis Su(var)3-9 homolog, was previously shown to be required for the expression of a few promoter methylated genes. By chromatin immunoprecipitation combined with sequencing, we demonstrate that SUVH1 binds to methylated genomic loci targeted by RNA-directed DNA methylation. SUVH1 and its homolog SUVH3 function partially redundantly and interact with three DNAJ domain-containing homologs, SDJ1, SDJ2, and SDJ3, thus forming a complex which we named SUVH-SDJ. The SUVH-SDJ complex components are co-localized in a large number of methylated promoters and are required for the expression of a subset of promoter methylated genes. We demonstrate that the SUVH-SDJ complex components have transcriptional activation activity. SUVH1 and SUVH3 function synergistically with SDJ1, SDJ2, and SDJ3 and are required for plant viability. This study reveals how the SUVH-SDJ complex protects promoter methylated genes from transcriptional silencing and suggests that the transcriptional activation of promoter methylated genes mediated by the SUVH-SDJ complex may play a critical role in plant growth and development.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Regiões Promotoras Genéticas/genética , Ativação Transcricional/fisiologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Metilação de DNA/genética , Metilação de DNA/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Ativação Transcricional/genética
19.
Mol Med Rep ; 19(2): 783-791, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30535469

RESUMO

The purpose of this review is to summarize the research progress of PI3K/Akt signaling pathway in erythropoiesis and glycolysis. Phosphatidylinositol­4,5­bisphosphate 3­kinase (PI3K) is activated by numerous genes and leads to protein kinase B (Akt) binding to the cell membrane, with the help of phosphoinositide­dependent kinase, in the PI3K/Akt signal transduction pathway. Threonine and serine phosphorylation contribute to Akt translocation from the cytoplasm to the nucleus and further mediates enzymatic biological effects, including those involved in cell proliferation, apoptosis inhibition, cell migration, vesicle transport and cell cancerous transformation. As a key downstream protein of the PI3K/Akt signaling pathway, hypoxia­inducible factor (HIF)­1 is closely associated with the concentration of oxygen in the environment. Maintaining stable levels of HIF­1 protein is critical under normoxic conditions; however, HIF­1 levels quickly increase under hypoxic conditions. HIF­1α is involved in the acute hypoxic response associated with erythropoietin, whereas HIF­2α is associated with the response to chronic hypoxia. Furthermore, PI3K/Akt can reduce the synthesis of glycogen and increase glycolysis. Inhibition of glycogen synthase kinase 3ß activity by phosphorylation of its N­terminal serine increases accumulation of cyclin D1, which promotes the cell cycle and improves cell proliferation through the PI3K/Akt signaling pathway. The PI3K/Akt signaling pathway is closely associated with a variety of enzymatic biological effects and glucose metabolism.


Assuntos
Eritropoese/fisiologia , Glicólise/fisiologia , Hipóxia/metabolismo , Hipóxia/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Animais , Humanos
20.
Pharmazie ; 72(4): 232-235, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29441994

RESUMO

MicroRNAs are found to be stable in blood and they demonstrated tissue specific expression patterns. Thus, they may be used as potential non-invasive biomarkers of specific cancers. In the current study, we mainly focused on miR-144, which has never been studied in acute myeloid leukemia (AML). The expression of miR-144 was explored in the bone marrow and peripheral blood of AML patients and healthy control. The correlation between peripheral blood miR-144 level and key clinical parameters, including overall survival and prognostic value, was further explored. We showed that miR-144 was markedly reduced in both the peripheral blood and bone marrow of AML patients compared with healthy controls. Further study revealed that there is a significant correlation between peripheral blood miR-144 level and FAB classification (p=0.0023) and cytogenetics (p=0.001). More importantly, a lower expression of peripheral blood miR-144 level was found to be positively correlated with poorer overall survival rate. In summary, peripheral blood miR-144 may be utilized as a potential novel non-invasive biomarker for AML screening.


Assuntos
Biomarcadores Tumorais/genética , Medula Óssea/metabolismo , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/patologia , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
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