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1.
ACS Appl Mater Interfaces ; 16(23): 29793-29804, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38819663

RESUMO

The effectiveness of photodynamic therapy (PDT) in treating brain gliomas is limited by the solubility of photosensitizers and the production of reactive oxygen species (ROS), both of which are influenced by the concentration of photosensitizers and catalyst active sites. In this study, we developed a controllable surface hydroxyl concentration for the photosensitizer CN11 to address its poor water solubility issue and enhance PDT efficacy in tumor treatment. Compared to pure g-C3N4 (CN), CN11 exhibited 4.6 times higher hydrogen peroxide production under visible light, increased incidence of the n → π* electron transition, and provided more available reaction sites for cytotoxic ROS generation. These findings resulted in a 2.43-fold increase in photodynamic treatment efficacy against brain glioma cells. Furthermore, in vivo experiments conducted on mice demonstrated that CN11 could be excreted through normal cell metabolism with low cytotoxicity and high biosafety, effectively achieving complete eradication of tumor cells.


Assuntos
Neoplasias Encefálicas , Glioma , Nitrilas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Glioma/tratamento farmacológico , Glioma/patologia , Glioma/metabolismo , Animais , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Nitrilas/química , Nitrilas/farmacologia , Humanos , Espécies Reativas de Oxigênio/metabolismo
2.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(3): 215-221, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38512031

RESUMO

Objective To compare the functional differences between bone marrow derived macrophages and peritoneal macrophages, which may provide the basis for the selection of macrophages in immunological research and immunoregulatory drug evaluation. Methods Marophage colony-stimulating factor (M-CSF) was used to induce the differentiation of bone marrow monocytes into macrophages, and thioglycolate medium was used to induce peritonitis to obtain peritoneal macrophages. After both macrophages being stimulated by zymosan, LPS, R848 and CpG respectively, mRNA levels of tumor necrosis factor α(TNF-α), interleukin 6(IL-6), macrophage inflammatory protein 1α(MIP-1α), monocyte chemoattractant protein 1(MCP-1) were measured by Real-time fluorescent quantitative PCR and the concentrations of secreted TNF-α, IL-6, MIP-1α and MCP-1 were detected by ELISA. In addition, the expression of costimulatory molecules CD80, CD86, CD40 and histocompatibility complex II (MHC II) on the cell surface was analyzed by flow cytometry. Results After inducing by different TLR ligands, mRNA expression levels of inflammatory cytokines and chemokines were increased in both macrophages. The secretion of TNF-α, IL-6, MIP-1α and MCP-1 in peritoneal macrophages and the expression of CD86 and MHC II on the surface of peritoneal macrophages were significantly higher than those of bone marrow derived macrophages. Conclusion There are significant differences in the expression of inflammatory factors, chemokines, costimulatory molecules, and histocompatibility complex between bone marrow derived macrophages and peritoneal macrophages. Peritoneal macrophages have more complete macrophage function and is more suitable for immunological research and immunomodulatory drug evaluation.


Assuntos
Medula Óssea , Cavidade Peritoneal , Animais , Camundongos , Quimiocina CCL3/genética , Interleucina-6 , Fator de Necrose Tumoral alfa , Macrófagos , Antígeno B7-1 , Antígenos CD40 , RNA Mensageiro
3.
Biochem Biophys Res Commun ; 703: 149647, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38350211

RESUMO

The establishment of an osseointegration is crucial for the long-term stability and functionality of implant materials, and early angiogenesis is the key to successful osseointegration. However, the bioinertness of titanium implants affects osseointegration, limiting their clinical application. In this study, inspired by the rapid polarization of macrophages following the phagocytosis of bacteria, we developed bacteroid cerium oxide particles; these particles were composed of CeO2 and had a size similar to that of Bacillus (0.5 µ m). These particles were constructed on the implant surfaces using a hydrothermal method. In vitro experiments demonstrated that the particles effectively decreased the reactive oxygen species (ROS) levels in macrophages (RAW264.7). Furthermore, these particles exerted effects on M1 macrophage polarization, enhanced nitric oxide (NO) secretion to promote vascular regeneration, and facilitated rapid macrophage transition to the M2 phenotype. Subsequently, the particles facilitated human umbilical vein endothelial cell (HUVEC) migration. In vivo studies showed that these particles rapidly stimulated innate immune responses in animal models, leading to enhanced angiogenesis around the implant and improved osseointegration. In summary, the presence of bacteroid cerium oxide particles on the implant surface regulated and accelerated macrophage polarization, thereby enhancing angiogenesis during the immune response and improving peri-implant osseointegration.


Assuntos
Cério , Osseointegração , Animais , Humanos , Macrófagos , Cério/farmacologia , Imunidade Inata , Neovascularização Patológica , Titânio , Osteogênese , Propriedades de Superfície
4.
Eur J Pharmacol ; 963: 176247, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056617

RESUMO

Neurogenesis is known to be closely associated with depression. We aimed to investigate whether a polypeptide monomer derived from pilose antler (polypeptide sequence LSALEGVFYP, PAP) exerts an antidepressant effect by influencing neurogenesis, and to elucidate the mechanism of its antidepressant action. Behavioral tests were performed to observe the antidepressant effect of PAP. Neurogenesis in the dentate gyrus (DG) region of hippocampus was observed by immunofluorescence. The expression of key proteins of Sentrin/SUMO-specific proteases 2 (SENP2)- Phosphoinositide-specific phospholipase C beta 4 (PLCß4) pathway was accessed by co-immunoprecipitation (Co-IP), and the calcium homeostasis associated proteins were observed via Western blot (WB). Subsequently, temozolomide (TMZ) pharmacologically blocked neurogenesis to verify the antidepressant effect of PAP on neurogenesis. The mechanism of PAP antidepressant effect was verified by constructing a sh-SENP2 virus vector to silence SENP2 protein. Finally, corticosterone (CORT)-induced PC12 cell model was used to verify whether PAP was involved in the process of deconjugated PLCß4 SUMOylated. The results showed that PAP improved depression-like behavior and neurogenesis induced by chronic unpredictable mild stimulation (CUMS). In addition, PAP acted on SENP2-PLCß4 pathway to deconjugate the SUMOylation of PLCß4 and affect calcium homeostasis. Pharmacological blockade of neurogenesis by TMZ treatment impaired the antidepressant efficacy of PAP. Knockout of SENP2 in the CUMS model attenuated the antidepressant response of PAP, and the impaired neurogenesis was not ameliorated by PAP treatment. In summary, PAP acted on the SENP2-PLCß4 signaling pathway to inhibit the SUMOylation of PLCß4 and maintain calcium homeostasis, thereby protecting neurogenesis and playing an antidepressant role.


Assuntos
Depressão , Peptídeo Hidrolases , Animais , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/metabolismo , Fosfolipase C beta/metabolismo , Peptídeo Hidrolases/farmacologia , Cálcio/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/metabolismo , Transdução de Sinais , Peptídeos/farmacologia , Endopeptidases/metabolismo , Endopeptidases/farmacologia , Hipocampo , Estresse Psicológico/metabolismo , Modelos Animais de Doenças
5.
Zhongguo Zhong Yao Za Zhi ; 48(10): 2803-2809, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37282940

RESUMO

This study aimed to explore the potentiating effect and mechanism of the extract of Jingfang Granules(JFG) on the activation of macrophages. The RAW264.7 cells were treated with JFG extract and then stimulated by multiple agents. Subsequently, mRNA was extracted, and reverse transcription-polymerase chain reaction(RT-PCR) was used to measure the mRNA transcription of multiple cytokines in RAW264.7 cells. The levels of cytokines in the cell supernatant were detected by enzyme-linked immunosorbent assay(ELISA). In addition, the intracellular proteins were extracted and the activation of signaling pathways was determined by Western blot. The results showed that JFG extract alone could not promote or slightly promote the mRNA transcription of TNF-α, IL-6, IL-1ß, MIP-1α, MCP-1, CCL5, IP-10, and IFN-ß, and significantly enhance the mRNA transcription of these cytokines in RAW264.7 cells induced by R848 and CpG in a dose-dependent manner. Furthermore, JFG extract also potentiated the secretion of TNF-α, IL-6, MCP-1, and IFN-ß by RAW264.7 cells stimulated with R848 and CpG. As revealed by mechanism analysis, JFG extract enhanced the phosphorylation of p38, ERK1/2, IRF3, STAT1, and STAT3 in RAW264.7 cells induced by CpG. The findings of this study indicate that JFG extract can selectively potentiate the activation of macrophages induced by R848 and CpG, which may be attributed to the promotion of the activation of MAPKs, IRF3, and STAT1/3 signaling pathways.


Assuntos
Interleucina-6 , Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos , Citocinas/genética , Citocinas/metabolismo , RNA Mensageiro/metabolismo
6.
ACS Appl Mater Interfaces ; 11(22): 20037-20044, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31071261

RESUMO

A paraffin microsphere-templated 3D porous EcoFlex sponge was prepared to selectively absorb oil or chemicals from water. The technology for producing this EcoFlex sponge does not need complicated synthesis processes or instruments, and the materials applied in this work are ecofriendly. Therefore, this sponge can be employed in the environmental field. EcoFlex sponges showed high hydrophobicity (contact angle = 140-143°) and oleophilicity. The developed sponge exhibits a porous three-dimensional framework inside with excellent internal connectivity, which contributes both better absorption capacity and faster absorption rate. For instance, the absorption capacity for chloroform can reach 3400 wt %. The absorption capacity of the sponge was optimized using different size of paraffin microspheres and these sponges exhibit relatively high absorption capacity in a short time (2 min). The volume of sponge expands in some oils and organic solvents: the increased volume capacity for hexane can reach 2200%. This sponge also has great recovery capability and durability; it keeps its original shape and absorption capacity after 15 cycles of oil absorption and compression.

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