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1.
Mol Cell Biochem ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376663

RESUMO

Atherosclerosis (AS) is a pivotal pathological basis of cardiovascular and cerebrovascular diseases, and circular RNAs (circRNAs) has been disclosed to exert a vital part in the progression of AS. However, the functions of circ_0004872 in the progression of AS is indistinct. In this context, we aimed to elucidate the role of circ_0004872 and the potential mechanism in AS. The level of circ_0004872, miR-424-5p and fibroblast growth factor receptor substrate 2 (FRS2) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was monitored by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine (EDU) assays. The invasion and migration capabilities of VSMCs were tested by transwell assays and wound-healing assay, respectively. Western blot was adopted to check the protein levels of CyclinD1, Vimentin and FRS2. Dual-luciferase reporter and RNA immunoprecipitation assay were executed to manifest the interaction between miR-424-5p and circ_0004872 or FRS2. The level of circ_0004872 was increased in the serum samples of AS patients and ox-LDL-exposed VSMCs. Ox-LDL exposure triggered cell proliferation, invasion and migration ability of VSMCs. depletion of circ_0004872 partly weakened ox-LDL-mediated effects in VSMCs. Mechanistically, circ_0004872 functioned as a sponge of miR-424-5p, and miR-424-5p inhibition partly alleviated circ_0004872 deficiency-mediated influences in VSMCs. Additionally, miR-424-5p interacted with FRS2, and miR-424-5p constrained dysfunction in ox-LDL-stimulated VSMCs via reducing FRS2 level. Notably, circ_0004872 functioned as a sponge of miR-424-5p to elevate FRS2 expression. Circ_0004872 accelerated ox-LDL-induced damage via mediating miR-424-5p/FRS2 axis.

2.
Molecules ; 29(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38611920

RESUMO

Six new 2α-hydroxy ursane triterpenoids, 3α-cis-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (1), 3α-trans-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (2), 3α-trans-p-coumaroyloxy-2α-hydroxy-12-ursen-28-oic acid (3), 3ß-trans-p-coumaroyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (4), 3ß-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (5), and 3α-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (6), along with eleven known triterpenoids (7-17), were isolated from the leaves of Diospyros digyna. Their chemical structures were elucidated by comprehensive analysis of UV, IR, HRESIMS, and NMR spectra. All the isolated compounds were evaluated for their PTP1B inhibitory activity. 3ß-O-trans-feruloyl-2α-hydroxy-urs-12-en-28-oic acid (13) showed the best inhibition activity with an IC50 value of 10.32 ± 1.21 µM. The molecular docking study found that the binding affinity of compound 13 for PTP1B was comparable to that of oleanolic acid (positive control).


Assuntos
Diospyros , Triterpenos , Simulação de Acoplamento Molecular , Folhas de Planta , Hidroxiácidos , Triterpenos/farmacologia
3.
Molecules ; 28(22)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-38005186

RESUMO

To disperse fatty acids in aqueous solution, choline, a quaternary ammonium ion, has been used recently. So far, only the self-assembly of myristic acid (MA) in the presence of choline hydroxide as a function of the molar ratio has been investigated, and, thus, the current understanding of these fatty acid systems is still limited. We investigated the self-assembly of palmitic acid (PA) in the presence of choline hydroxide (ChOH) as a function of the molar ratio (R) between ChOH and PA. The self-assemblies were characterized by phase contrast microscopy, cryo-TEM, small-angle X-ray scattering, and 2H NMR. The ionization state of PA was determined by pH, conductivity, and FT-IR measurements. With increase in R, various self-assembled structures, including vesicles, lamellar phase, rigid membranes (large sheets, tubules, cones, and polyhedrals), and micelles, form in the PA/ChOH system, different from those of the MA/ChOH system. The change in R induces pH variation and, consequently, a change in the PA ionization state, which, in turn, regulates the molecular interactions, including hydrogen bonding and electrostatic interaction, leading to various self-assemblies. Temperature is an important factor used to tune the self-assembly transitions. The fatty acid choline systems studied here potentially may be applicable in medicine, chemical engineering, and biotechnology.

4.
Environ Monit Assess ; 195(12): 1537, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38010577

RESUMO

Understanding the spatial expansion process of salt marshes and quantifying the factors driving this expansion are crucial for the management and restoration of coastal wetlands. In this study, we aimed to illustrate the expansion process of Scirpus mariqueter using drone remote sensing and quantify its relationship with habitat quality. Our hypothesis was that landscape metrics could serve as valuable indicators for prioritizing habitat restoration efforts along the coast. We utilized drone remote sensing and adopted the simple Greenness Index to reflect the growth status of S. mariqueter. Using this index, we computed the standard deviation ellipse and growth center. To evaluate habitat quality, we developed a method based on our previous research and other relevant reports. We then conducted a quantitative analysis of the expansion process of S. mariqueter in areas with varying habitat quality. We found that S. mariqueter's optimal elevation was 3.7 m, with a range of 2.5 to 4.3 m. The threshold value for soil total nitrogen was 0.3 g/kg, and the tolerance threshold for soil salinity was 2500 ppm. These three factors, elevation, soil total nitrogen, and soil salinity, collectively influenced habitat quality, with weights of 0.68, 0.23, and 0.09, respectively, as determined through geodetector analysis. During the summer, we observed a dominance of dispersal in S. mariqueter, with the species primarily spreading to areas with increased habitat quality. Patch shapes tended to be compact and regular in this season. In contrast, during the autumn, a dominance of decline was observed, with S. mariqueter mainly distributing to areas exhibiting decreased habitat quality. Patch shapes tended to be complex and irregular in the autumn season. Eventually micro-geomorphic modification and patch shape filling methods based on UAV observations are proposed to aid wetland restoration. These findings are of utmost importance for the restoration of coastal wetlands and the enhancement of ecosystem resilience.


Assuntos
Cyperaceae , Áreas Alagadas , Ecossistema , Dispositivos Aéreos não Tripulados , Monitoramento Ambiental , Solo , Nitrogênio/análise
5.
Soft Matter ; 17(9): 2490-2499, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33503106

RESUMO

Simple single-chain amphiphiles (SCAs) can form vesicular structures in their single-component aqueous solutions, which has attracted great attention, but the understanding of their aggregation behavior is still limited. In this work, the aggregation behavior of 4-dodecylbenzene sulfonic acid (DBSA), a typical simple SCA, in water was investigated. The structure and properties of the aggregates formed were determined. In particular, the effect of wet-dry cycles on the structures of aggregates was examined. The mechanisms of aggregate formation and structural transition were discussed. It was found that the increase of DBSA concentration can drive the occurrence of a micelle-to-vesicle transition, showing a critical micelle concentration and critical vesicle concentration of ∼0.53 and 2.14 mM, respectively. The vesicles formed coexist with micelles in solution, with a unilamellar structure and ∼80 nm size, and exhibit size-selective permeability. In addition, the vesicles show remarkable stability upon long-term storage, exposure to high temperature, and freeze-thaw cycles. The H-bonding interaction between DBSA species and the interdigitated structure of alkyl chains in bilayers play a key role in the formation and stability of DBSA vesicles. Interestingly, it was found that the wet-dry cycle can induce a micelle-to-vesicle transition and an obvious increase in the size of the original vesicles, accompanied by the formation of some multilamellar vesicles. This work provides a better understanding of the aggregation behavior of simple SCAs in their single-component aqueous solutions.

6.
Soft Matter ; 17(17): 4604-4614, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33949616

RESUMO

Monoalkyl phosphates (MAPs) are one kind of important single-chain weak acid/salt type surfactants, but the understanding of their aggregation behavior in water is very limited due to their insolubility at room temperature. In the current work, the effect of guanidinium salts (GuSalts) on the solubility of sodium monododecylphosphate (SDP), a typical MAP, in water was determined at 25.0 °C, and the aggregation behavior of SDP in the GuSalt/water mixtures was investigated. The solubility of SDP is significantly improved by GuSalts including GuCl, GuSO4, GuSO3, GuPO4, and GuCO3 at 25.0 °C, resulting in an isotropic phase. SDP vesicles are spontaneously formed in the isotropic phase, with a critical vesicle concentration of ∼1.0 mM independent of the type of GuSalts. A "bridging dimer" mechanism is proposed to explain the formation of SDP vesicles. The SDP vesicles have a unilamellar structure with a size of ∼80 nm and an alkyl interdigitated degree of ∼25%, and exhibit size-selective permeability. Interestingly, a temperature-induced reversible transition between vesicles and α-gels was observed for the SDP/GuSalt/H2O systems when the SDP content is higher than 20 mM. The α-gels obtained are composed of vesicles and bilayer sheets, showing similar viscoelasticity to conventional gels, although their water content is as high as ∼98 wt%. The microviscosity of SDP vesicle membranes (ca. 35.79-49.34 mPa s at 25.0 °C) and the transition temperature between vesicles and α-gels (ca. 21.0-22.8 °C) are all dependent of the type of GuSalts. This work deepens the understanding of the aggregation behavior of MAPs and also provides valuable information for their practical applications.

7.
Molecules ; 25(6)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168948

RESUMO

Psidium guajava, a popular food and medicine dual purposes plant cultivated in tropical and subtropical regions, has been widely used as food crop and folk medicine, such as anti-diabetes agent, around the world. Triterpenoids have been considered as the major active ingredients of P. guajava. In the present study, a high-performance liquid chromatography coupled with diode array and evaporative light scattering detectors (HPLC-DAD-ELSD) method was developed for simultaneous determination of nine triterpenoids in P. guajava. Pressurized liquid extraction (PLE) was performed for sample preparation, and the analysis was achieved on a Cosmosil 5C18-MS-II (Nacalai Tesque, Kyoto, Japan) column eluted with gradient 0.1% aqueous formic acid-methanol system. The drift tube temperature of ELSD was set at 40 °C, and nitrogen flow-rate was at 1.6 L/min. All calibration curves for the analytes showed good linear regression (R2 > 0.9992) within test ranges. The established method was validated for intra-day and inter-day precisions (RSDs < 5%) and accuracy (recovery 94.23-106.87%). The validated method was successfully applied to determinate nine triterpenoids in 15 samples from the leave or fruit of P. guajava. In addition, the α-glucosidase inhibition assay showed good α-glucosidase inhibition activity in almost all the determined triterpenoids. The present study suggested that triterpenoids should be the quality control markers for P. guajava and HPLC-DAD-ELSD was an effective tool for the quality control of P. guajava.


Assuntos
Medicamentos de Ervas Chinesas/química , Inibidores de Glicosídeo Hidrolases/química , Hipoglicemiantes/química , Psidium/química , Triterpenos/química , alfa-Glucosidases/química , Calibragem , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Formiatos/química , Frutas/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Hipoglicemiantes/isolamento & purificação , Extração Líquido-Líquido/métodos , Metanol/química , Variações Dependentes do Observador , Folhas de Planta/química , Controle de Qualidade , Solventes/química , Triterpenos/isolamento & purificação
8.
Cancer Cell Int ; 19: 9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30636930

RESUMO

BACKGROUND: T-acute lymphoblastic leukemia (T-ALL) was a hematological malignancy characterized by the accumulation of immature T cells in bone marrow and peripheral blood. In this study, we tried to explore the physiological role of CD59 in T-ALL. METHODS: In this study, we collected the bone marrow samples from 17 T-ALL patients and 38 healthy participants to find differences in CD59 expression patterns. Then, CD59 was over-expressed in T-ALL cell line Jurkat, and its biological functions were detected. In addition, in order to understand the active site of CD59, the Trp40 was mutated. Further, we constructed a mouse model by transplanting Jurkat cells into the nude mice to verify the function of CD59 in vitro. At last, mechanism studies were performed by western blot. RESULTS: We found that the proportion of T lymphocytes expressing CD59 in bone marrow of T-ALL patients was significantly higher than that of healthy individuals. Then, we found that the overexpression of CD59 in Jurkat cells was beneficial to the cell survival by inhibiting apoptosis and promoting IL-2 secretion. In this process, Trp40 of CD59 was a key functional site. Further, the high expression of CD59 inhibited apoptosis of bone marrow and peripheral blood cells, and promoted IL-2 secretion in mouse model. At last, mechanism studies showed that the activation of AKT, STAT5 and Notch1 signaling pathways in Jurkat cells, may be involved in the regulation of apoptosis by CD59; and mutation in the Trp40 affect the interaction of CD59 with these signaling pathways. CONCLUSIONS: In conclusion, CD59 inhibited apoptosis of T-ALL by regulating AKT/Notch1 signaling pathway, providing a new perspective for the treatment of T-ALL.

9.
Phys Chem Chem Phys ; 20(5): 3843, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29359777

RESUMO

Correction for 'Model of protocell compartments - dodecyl hydrogen sulfate vesicles' by Bin Liu et al., Phys. Chem. Chem. Phys., 2018, DOI: .

10.
Phys Chem Chem Phys ; 20(3): 1332-1336, 2018 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-29292420

RESUMO

Dodecyl hydrogen sulfate (DHS), a simple single-alkyl sulfonic acid, can form vesicles spontaneously in water without any additives close to its apparent pKa. Interestingly, DHS vesicles show typical characteristics of primitive cell membranes in respect of selective permeability, fast exchange, self-reproduction and stability under primordial environments.

11.
Heliyon ; 10(11): e32686, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38961957

RESUMO

Periodontitis is an inflammatory disease characterized by the destruction of periodontal tissues, and the promotion of bone tissue regeneration is the key to curing periodontitis. Psoralen is the main component of Psoralea corylifolia Linn, and has multiple biological effects, including anti-osteoporosis and osteogenesis. We constructed a novel hydrogel loaded with psoralen (PSO) and stromal cell-derived factor-1 (SDF-1) for direct endogenous cell homing. This study aimed to evaluate the synergistic effects of PSO/SDF-1 on periodontal bone regeneration in patients with periodontitis. The results of CCK8, alkaline phosphatase (ALP) activity assay, and Alizarin Red staining showed that PSO/SDF-1 combination treatment promoted cell proliferation, chemotaxis ability, and ALP activity of PDLSCs. qRT-PCR and western blotting showed that the expression levels of alkaline phosphatase (ALP), dwarf-associated transcription factor 2 (RUNX2), and osteocalcin (OCN) gene were upregulated. Rat periodontal models were established to observe the effect of local application of the composite hydrogel on bone regeneration. These results proved that the PSO/SDF-1 combination treatment significantly promoted new bone formation. The immunohistochemical (IHC) results confirmed the elevated expression of ALP, RUNX2, and OCN osteogenic genes. PSO/SDF-1 composite hydrogel can synergistically regulate the biological function and promote periodontal bone formation. Thus, this study provides a novel strategy for periodontal bone regeneration.

12.
Iran J Immunol ; 20(1): 67-75, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36932952

RESUMO

Background: The extent to which maternal antibodies against the hepatitis B surface antigen (HBsAb) acquired transplacentally affect the immune responses to the hepatitis B vaccine (HBVac) in infants is still uncertain. Objective: To explore the impact of the HBsAb on the immune response to the HBVac in a mouse model. Methods: According to the doses of the HBVac (2, 5 µg) injected, 267 BALB/c mice were divided into two groups. Each group was subdivided into 3 subgroups based on the doses of the hepatitis B immunoglobulin (HBIG) (0, 25, 50 IU) administered. The HBsAb titers were detected 4 weeks after completing the HepB vaccination. Results: Among all the mice, 40 had an HBsAb titer <100 mIU/mL (non- or low-response to the HBVac). The rates of the HBsAb titer <100 mIU/mL in 0, 25 and 50 IU HBIG groups were 1.1%, 23.1%, and 20.7%, respectively. Multivariate logistic regression analysis showed that the risk factors for low- or non-response to the HBVac were injection with the HBIG, low HBVac dose, and hypodermic injection. The mean HBsAb titers (log10) reduced gradually in the 0, 25 and 50 IU HBIG groups (P<0.001). Conclusion: The HBIG administration has negative impacts on the peak level of the HBsAb and the rate of an effective immune response. This implies that the maternal HBsAb acquired transplacentally might inhibit the immune responses to the HBVac in infants.


Assuntos
Vacinas contra Hepatite B , Hepatite B , Animais , Camundongos , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Imunidade
13.
Arch Oral Biol ; 156: 105810, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37852106

RESUMO

OBJECTIVE: The aim of this study was to explore the role of the tumor suppressor phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) on oral squamous cell carcinoma (OSCC) and its molecular mechanism. DESIGN: Immunohistochemistry detected the expression of PAG1 in normal and tumor tissues. The PAG1 overexpressed OSCC cell lines were constructed by lentivirus transfection. Cell Counting Kit-8 assay (CCK-8), clone formation and flow cytometry evaluated the impact of PAG1 on the proliferation and apoptosis of OSCC cells. RNA sequencing (RNA-seq) detected the changes in intracellular genes, and transmission electron microscope (TEM) was used to compare the number of autophagosomes in OSCC cells between Negative and PAG1 group. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot were used to determine the expression of signaling pathway-related mRNA and proteins respectively. RESULTS: In contrast to the normal tissues, PAG1 expression was significantly downregulated in tumor tissues. Treatment with lentivirus transfection, the expression of PAG1 in the OSCC cell lines was increase. Notably, transfected with PAG1-overexpressing lentivirus cells inhibited the proliferation of OSCC cells and promoted OSCC cells apoptosis. RNA-seq revealed that PAG1 mainly modulated the mitophagy and autophagy pathway, and many autophagosomes were observed in the PAG1 group using TEM. Mechanistically, we found that PAG1 upregulated the expression of autophagy related factors through inhibiting PI3K/Akt/mTOR signal pathway activation. CONCLUSION: Overexpression of PAG1 inhibited OSCC progression by activating autophagy, its mechanism might be related to inhibition of PI3K/Akt/mTOR signal pathway phosphorylation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Membrana , MicroRNAs , Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , Neoplasias Bucais/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Serina-Treonina Quinases TOR/metabolismo
14.
Hum Cell ; 36(4): 1389-1402, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37269415

RESUMO

Periodontitis is a chronic inflammatory disease that is the main cause of tooth loss in adults, and the key to periodontitis treatment is the repair and regenerate of periodontal bone tissue. Psoralen is the main component of the Psoralea corylifolia Linn, which shows antibacterial, anti-inflammatoryand osteogenic activities. It promotes the differentiation of periodontal ligament stem cells toward osteogenesis. Exosomes secreted by stem cells play important roles in information transmission during the osteogenic differentiation process. The aim of this paper was to investigate the role of psoralen in regulating osteogenic miRNA information in periodontal stem cells and in periodontal stem cells exosomes and the specific mechanism of its action. Experimental results show that exosomes of human periodontal ligament stem cell origin treated with psoralen (hPDLSCs + Pso-Exos) were not significantly different from untreated exosomes (hPDLSC-Exos) in terms of size and morphology. Thirty-five differentially expressed miRNAs were found to be upregulated and 58 differentially expressed miRNAs were found to be downregulated in the hPDLSCs + Pso-Exos compared to the hPDLSC-Exos (P < 0.05). hsa-miR-125b-5p was associated with osteogenic differentiation. Among them, hsa-miR-125b-5p was associated with osteogenic differentiation. After hsa-miR-125b-5p was inhibited, the osteogenesis level of hPDLSCs was enhanced. In summary, the osteogenic differentiation of hPDLSCs was promoted by psoralen through the downregulation of hsa-miR-125b-5p gene expression in hPDLSCs, and the expression of the hsa-miR-125b-5p gene was also downregulated in exosomes. This finding provides a new therapeutic idea for using psoralen to promote periodontal tissue regeneration.


Assuntos
Exossomos , MicroRNAs , Adulto , Humanos , Osteogênese/genética , Exossomos/genética , Ficusina/farmacologia , Ficusina/metabolismo , Células Cultivadas , MicroRNAs/metabolismo , Células-Tronco/fisiologia , Diferenciação Celular/genética , Ligamento Periodontal
15.
Infect Immun ; 80(1): 429-40, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22083709

RESUMO

Aspergillus fumigatus is the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases on A. fumigatus virulence is rather limited. In this study, disruption of the pld gene encoding phospholipase D (PLD), an important member of the phospholipase protein family in A. fumigatus, was confirmed to significantly decrease both intracellular and extracellular PLD activity of A. fumigatus. The pld gene disruption did not alter conidial morphological characteristics, germination, growth, and biofilm formation but significantly suppressed the internalization of A. fumigatus into A549 epithelial cells without affecting conidial adhesion to epithelial cells. Importantly, the suppressed internalization was fully rescued in the presence of 100 µM phosphatidic acid, the PLD product. Indeed, complementation of pld restored the PLD activity and internalization capacity of A. fumigatus. Phagocytosis of A. fumigatus conidia by J774 macrophages was not affected by the absence of the pld gene. Pretreatment of conidia with 1-butanol and a specific PLD inhibitor decreased the internalization of A. fumigatus into A549 epithelial cells but had no effect on phagocytosis by J774 macrophages. Finally, loss of the pld gene attenuated the virulence of A. fumigatus in mice immunosuppressed with hydrocortisone acetate but not with cyclophosphamide. These data suggest that PLD of A. fumigatus regulates its internalization into lung epithelial cells and may represent an important virulence factor for A. fumigatus infection.


Assuntos
Aspergillus fumigatus/enzimologia , Aspergillus fumigatus/patogenicidade , Deleção de Genes , Fosfolipase D/metabolismo , Fatores de Virulência/metabolismo , Animais , Aspergillus fumigatus/crescimento & desenvolvimento , Aspergillus fumigatus/fisiologia , Biofilmes/crescimento & desenvolvimento , Adesão Celular , Linhagem Celular , Células Epiteliais/microbiologia , Teste de Complementação Genética , Humanos , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fagocitose , Fosfolipase D/genética , Esporos Fúngicos/patogenicidade , Virulência , Fatores de Virulência/genética
16.
J Cell Biochem ; 113(12): 3810-22, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22821302

RESUMO

Some short peptides discovered by phage display are found to be able to inhibit cancer growth and induce cancer cell apoptosis. In this study, a novel cancer-targeting short peptide which was composed of 22 amino acids (ACHWPWCHGWHSACDLPMHPMC, abbreviated as sp22) and specifically bound to human CD59 was screened from a M13 phage display library so as to counteract tumor immune escape activity. The mechanism of exogenous sp22 peptide in inducing apoptosis of MCF-7 cells was investigated. The results suggested that sp22 could lower CD59 expression level, downregulate Bcl-2 expression, activate Fas and caspase-3, and finally increase apoptotic cell numbers of MCF-7 cells. However, sp22 had no obvious influence on normal human embryonic lung cells. In addition, the effects of endogenous sp22 gene on CD59 expression and NKM cell apoptosis were explored using the recombinant plasmid sp22-PIRES. It showed that sp22 gene was efficiently expressed in transfected NKM cells. Compared with normal NKM cells, NKM cells transfected with sp22 displayed reduced mRNA and protein expression levels of CD59, increased sensitivity to complement-mediated cytolysis, decreased cell survival ratio, changes of the expression of apoptosis associated proteins, increased number of apoptotic cells and the appearance of apoptotic morphology. The results suggested that sp22 protein could bind to CD59 and inhibit the expression of CD59. The cytolytic activity of complement on tumor cells strengthened and apoptosis signal was stepwise transferred which might be a potential way to kill tumor cells.


Assuntos
Apoptose , Antígenos CD59/metabolismo , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Antineoplásicos/farmacologia , Bacteriófago M13/genética , Sequência de Bases , Biomarcadores Tumorais , Antígenos CD59/efeitos dos fármacos , Células CHO , Caspase 3/genética , Caspase 3/metabolismo , Domínio Catalítico , Contagem de Células , Proliferação de Células , Sobrevivência Celular , Ativação do Complemento , Cricetinae , Ciclina D1/genética , Ciclina D1/metabolismo , Regulação Neoplásica da Expressão Gênica , Terapia Genética/métodos , Humanos , Marcação In Situ das Extremidades Cortadas , Células MCF-7 , Dados de Sequência Molecular , Biblioteca de Peptídeos , Peptídeos/síntese química , Plasmídeos/genética , Plasmídeos/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transfecção , Evasão Tumoral , Receptor fas/genética , Receptor fas/metabolismo
17.
Cell Immunol ; 274(1-2): 1-11, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22480874

RESUMO

CD59 is a complement regulatory protein known to prevent the membrane attack complex (MAC) from assembling. To investigate the role of CD59 molecules in human T cell activation in response to exogenous antigens, gene silencing via small interfering RNAs (siRNAs) was carried out. Subsequent T cell activation in response to both autologous dendritic cells (DCs) loaded with tumor lysate and beads coated with anti-CD3, anti-CD28 and anti-CD59 antibodies was investigated. The findings demonstrated that decreased CD59 expression on T cells significantly enhanced activation and proliferation of CD4(+) T cells and CD8(+) T cells while the expansion of CD4(+) CD25(+) regulatory T cells (Tregs) was not affected, and CD59 mediated inhibition of T cell activation requires the binding of CD59 with its ligand on antigen-presenting cells (APCs). The data support that CD59 down-regulates antigen-specific activation of human T lymphocytes in a ligand-dependent manner.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Antígenos CD59/genética , Antígenos CD59/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Neoplasias/imunologia , Interferência de RNA , Animais , Anticorpos Monoclonais/imunologia , Antígenos CD28/imunologia , Complexo CD3/imunologia , Linfócitos T CD4-Positivos/metabolismo , Antígenos CD59/biossíntese , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Células Dendríticas/metabolismo , Humanos , Ativação Linfocitária , Camundongos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
18.
J Asian Nat Prod Res ; 14(2): 135-40, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22296154

RESUMO

Two new methyl-migrated 16,17-seco-dammarane triterpenoid saponins, named acerboside A (1) and acerboside B (2), were isolated from the seeds of Hovenia acerba. Their structures were elucidated on the basis of spectroscopic analysis and hydrolysis.


Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Rhamnaceae/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Saponinas/química , Sementes/química , Triterpenos/química , Damaranos
19.
Front Bioeng Biotechnol ; 10: 878456, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35387305

RESUMO

The treatment of oral squamous cell carcinoma (OSCC) remains a great clinical challenge, and the malignant proliferation of OSCC cells can lead to the overexpression of CD59. In this study, a novel microsphere (ICT-CMC-CD59sp) composed of icariin (ICT), carboxymethyl chitosan (CMC), and cell differentiation antigen 59-specific ligand peptide (CD59sp) was successfully prepared by using the emulsion cross-linking method. Through the guidance of CD59sp, the microspheres can target OSCC cells and play a therapeutic role (p < 0.01). The MTT test and trypan blue staining showed that the microspheres could promote the apoptosis of oral squamous cell carcinoma and had a significant difference (p < 0.01). In this study, the regulatory effect of the microspheres on OSCC cells was investigated at the cellular level, and its therapeutic effect on OSCC was discussed, which provided a new perspective for the targeted therapy of OSCC.

20.
Cell Immunol ; 272(1): 61-70, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22000275

RESUMO

The retroviral-vector-targeted CD59 gene (pSUPER-siCD59) was constructed and transfected into breast cells (MCF-7). The results demonstrated that the retroviral vector-mediated RNAi successfully suppressed human CD59 gene. The expression of CD59 decreased at both mRNA and protein levels. Knockdown of CD59 abrogated its protective effect on complement-mediated cytolysis. Fas and caspase-3 were remarkably upregulated, which induced apoptosis and tumor growth suppression in MCF-7 cells. In addition, overexpression of CD59 promoted the proliferation of MCF-7 cells and inhibited anti-apoptotic Bcl-2 expression. In conclusion, CD59 may be a promising target in the gene therapy of breast cancer.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/terapia , Antígenos CD59/metabolismo , Expressão Gênica/efeitos dos fármacos , Terapia de Alvo Molecular/métodos , RNA Interferente Pequeno/farmacologia , Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Antígenos CD59/genética , Antígenos CD59/imunologia , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proteínas do Sistema Complemento/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Inativação Gênica/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , RNA Interferente Pequeno/genética , Retroviridae , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Regulação para Cima/efeitos dos fármacos , Receptor fas/genética , Receptor fas/metabolismo
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