Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 49
Filtrar
1.
Drug Resist Updat ; 76: 101113, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39053384

RESUMO

Gliomas, the most common CNS (central nerve system) tumors, face poor survival due to severe chemoresistance exacerbated by hypoxia. However, studies on whether altered hypoxic conditions benefit for chemo-sensitivity and how gliomas react to increased oxygen stimulation are limited. In this study, we demonstrated that increased oxygen stimulation promotes glioma growth and chemoresistance. Mechanically, increased oxygen stimulation upregulates miR-1290 levels. miR-1290, in turn, downregulates PLCB1, while PLCB1 facilitates the proteasomal degradation of ß-catenin and active-ß-catenin by increasing the proportion of ubiquitinated ß-catenin in a destruction complex-independent mechanism. This process inhibits PLCB1 expression, leads to the accumulation of active-ß-catenin, boosting Wnt signaling through an independent mechanism and ultimately promoting chemoresistance in glioma cells. Pharmacological inhibition of Wnt by WNT974 could partially inhibit glioma volume growth and prolong the shortened survival caused by increased oxygen stimulation in a glioma-bearing mouse model. Moreover, PLCB1, a key molecule regulated by increased oxygen stimulation, shows promising predictive power in survival analysis and has great potential to be a biomarker for grading and prognosis in glioma patients. These results provide preliminary insights into clinical scenarios associated with altered hypoxic conditions in gliomas, and introduce a novel perspective on the role of the hypoxic microenvironment in glioma progression. Furthermore, the outcomes reveal the potential risks of utilizing hyperbaric oxygen treatment (HBOT) in glioma patients, particularly when considering HBOT as a standalone option to ameliorate neuro-dysfunctions or when combining HBOT with a single chemotherapy agent without radiotherapy.


Assuntos
Neoplasias Encefálicas , Resistencia a Medicamentos Antineoplásicos , Glioma , MicroRNAs , Oxigênio , Fosfolipase C beta , Via de Sinalização Wnt , beta Catenina , Glioma/tratamento farmacológico , Glioma/patologia , Glioma/genética , Glioma/terapia , Glioma/metabolismo , Animais , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Camundongos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Via de Sinalização Wnt/efeitos dos fármacos , Oxigênio/metabolismo , Fosfolipase C beta/metabolismo , Fosfolipase C beta/genética , beta Catenina/metabolismo , beta Catenina/genética , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fenótipo , Camundongos Nus
2.
Polymers (Basel) ; 15(20)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37896363

RESUMO

Simultaneously high-rate and high-safety lithium-ion batteries (LIBs) have long been the research focus in both academia and industry. In this study, a multifunctional composite membrane fabricated by incorporating poly(vinylidene fluoride) (PVDF) with magnesium carbonate hydroxide (MCH) nanofibers was reported for the first time. Compared to commercial polypropylene (PP) membranes and neat PVDF membranes, the composite membrane exhibits various excellent properties, including higher porosity (85.9%) and electrolyte wettability (539.8%), better ionic conductivity (1.4 mS·cm-1), and lower interfacial resistance (93.3 Ω). It can remain dimensionally stable up to 180 °C, preventing LIBs from fast internal short-circuiting at the beginning of a thermal runaway situation. When a coin cell assembled with this composite membrane was tested at a high temperature (100 °C), it showed superior charge-discharge performance across 100 cycles. Furthermore, this composite membrane demonstrated greatly improved flame retardancy compared with PP and PVDF membranes. We anticipate that this multifunctional membrane will be a promising separator candidate for next-generation LIBs and other energy storage devices, in order to meet rate and safety requirements.

3.
Front Neurol ; 14: 1184864, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37602239

RESUMO

Background: Acute necrotizing encephalopathy (ANE) is a devastating neurologic condition that can arise following a variety of systemic infections, including influenza and SARS-Cov-2. The clinical features of COVID-19-associated ANE in pediatric patients based on multi-case data have not yet been described and remain obscure. We reviewed 12 pediatric patients to better describe the clinical features of ANE with COVID-19. Methods: We retrospectively collected and summarized the clinical features of ANE in children with COVID-19. Clinical data were collected from 12 children, including their general status, clinical symptoms, laboratory tests, and neuroimaging features. Results: Among the subjects, 10 were over 5 years old and they accounted for 83.33%. A large percentage of those affected (66.67%) were females. The major manifestations included fever (100%), impaired consciousness (100%), and convulsions (75%). We determined that increased interleukin (IL)-6 and IL-10, and tumor necrosis factor-α and interferon gamma were not predictive of severe ANE and mortality in children with COVID-19 in this study. All children presented with abnormal neuroimaging with multiple and symmetrically distributed lesions, involving the thalamus, basal ganglia, cerebellum, and brain hemispheres. Eight of the 12 children died, resulting in a mortality rate of 66.67%, and 75% of these children were females. Importantly, we found the timely administration of mannitol after an acute onset of convulsions or disturbance of consciousness may be decreased the high mortality induced by ANE children with COVID-19. Conclusion: COVID-19 associated with ANE in children is characterized by sudden symptom onset, rapid disease progression, and high mortality.

4.
Phytomedicine ; 119: 155021, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37603974

RESUMO

BACKGROUND: Total saponins from Rhizoma Panacis Majoris (RPMTG) showed significant antitumour activity in our previous studies. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) with tumour-like characteristics have received attention as a therapeutic target for RA. However, the potential effect and mechanism of action of RPMTG against RA-FLS remain unclear. OBJECTIVE: The study investigated the therapeutic effect of RPMTG on adjuvant-induced arthritis (AIA) in rats, and the regulation effect and underlying mechanism on apoptosis, autophagy of RA-FLS. METHODS: The therapeutic effect of RPMTG was determined by the symptoms and signs of AIA rats. The production of inflammatory cytokines was detected by ELISA. Histopathological change of the ankle and synovial tissues were detected by HE staining. Flow cytometry, Hoechst 33342/PI staining, MDC staining, and TEM were used to determine the effects of RPMTG on apoptosis and autophagy. Western blotting was applied to detect the expression levels of proteins. RESULTS: In AIA rats, RPMTG treatment ameliorated paw swelling, and arthritis score, restored synovial histopathological changes, inhibited the expression of IL-6 and IL-1ß, exhibiting its potent anti-arthritis effect. In vitro, RPMTG depressed the proliferation of RA-FLS, arrested cell cycle in G0/G1 phase, and induced mitochondria-mediated apoptosis. Moreover, RPMTG significantly inhibited the autophagy in vivo and in vitro, proved by decreasing the expression of autophagy-related indicators (LC3II/LC3I, Beclin-1). Mechanistically, the study demonstrated that the activation of p38 MAPK and PI3K/Akt/mTOR pathways was mainly involved in the therapeutic effects of RPMTG. Interestingly, the effect of RPMTG on apoptosis was reversed after Rapamycin treatment, which preliminarily demonstrated that the inhibitory effect of RPMTG on autophagy was beneficial to the effect on inducing apoptosis. The regulation effect of RPMTG concurrently on apoptosis and autophagy revealed its unique advantages in RA treatment. CONCLUSION: RPMTG showed potent therapeutic effects on AIA rats and induced apoptosis, inhibited autophagy mainly through activating the p38 MAPK and PI3K/Akt/mTOR pathways in RA-FLS.


Assuntos
Artrite Experimental , Artrite Reumatoide , Sinoviócitos , Animais , Ratos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Artrite Reumatoide/tratamento farmacológico , Artrite Experimental/tratamento farmacológico
5.
Microb Ecol ; 85(3): 904-915, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35650293

RESUMO

Thermokarst lakes have long been recognized as biogeochemical hotspots, especially as sources of greenhouse gases. On the Qinghai-Tibet Plateau, thermokarst lakes are experiencing extensive changes due to faster warming. For a deep understanding of internal lake biogeochemical processes, we applied metagenomic analyses to investigate the microbial diversity and their biogeochemical roles in sediment and water of thermokarst lakes in the Yellow River Source Area (YRSA). Sediment microbial communities (SMCs) had lower species and gene richness than water microbial communities (WMCs). Bacteria were the most abundant component in both SMCs and WMCs with significantly different abundant genera. The functional analyses showed that both SMCs and WMCs had low potential in methanogenesis but strong in aerobic respiration, nitrogen assimilation, exopolyphosphatase, glycerophosphodiester phosphodiesterases, and polyphosphate kinase. Moreover, SMCs were enriched in genes involved in anaerobic carbon fixation, aerobic carbon fixation, fermentation, most nitrogen metabolism pathways, dissimilatory sulfate reduction, sulfide oxidation, polysulfide reduction, 2-phosphonopropionate transporter, and phosphate regulation. WMCs were enriched in genes involved in assimilatory sulfate reduction, sulfur mineralization, phosphonoacetate hydrolase, and phosphonate transport. Functional potentials suggest the differences of greenhouse gas emission, nutrient cycling, and living strategies between SMCs and WMCs. This study provides insight into the main biogeochemical processes and their properties in thermokarst lakes in YRSA, improving our understanding of the roles and fates of these lakes in a warming world.


Assuntos
Lagos , Metagenômica , Lagos/microbiologia , Água , Rios , Nitrogênio , Sulfatos
6.
Curr Pharm Des ; 28(39): 3231-3241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36165527

RESUMO

BACKGROUND: In recent years, the prevalence and mortality of autism spectrum disorder (ASD) have been increasing. The clinical features are different with different cases, so the treatment ways are different for each one. OBJECTIVE: Baohewan Heshiwei Wen Dan Tang (BHWDT) has been recommended for treating autistic spectrum disorder. To investigate the mechanism of action and how the compounds interact with ASD targets, network pharmacology and molecular docking methods were used in this study. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the active components according to index of oral bio-activity and drug-likeness. Then, TCMSP and Swiss Target Prediction databases were used to screen potential target genes of active components. The related target genes of ASD were obtained from the Gene Cards database. Matescape database was utilized to get gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway annotation of gene targets. Composition- target-pathway (C-T-P) and a protein-protein interaction (PPI) networks were built with Cytoscape 3.8.2 software. RESULTS: The interaction of the main active components of BHWDT was verified by molecular docking. The key targets of MAPK1, IL6, CXCL8 and TP53 of BHWDT were obtained. The key active components Quercetin, Kaempferol and Iuteolin of BHWDT could bind with MAPK1, IL6, CXCL8 and TP53 of BHWDT, respectively. CONCLUSION: BHWDT can be highly effective for treating ASD and this study can help us to understand multiple targets and multiple pathways mechanism.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Medicamentos de Ervas Chinesas , Humanos , Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/genética , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/genética , Simulação de Acoplamento Molecular , Interleucina-6 , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa
7.
Mol Plant Pathol ; 23(12): 1815-1829, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36052490

RESUMO

Nonspecific lipid transfer proteins (LTPs) are small, cysteine-rich proteins that play numerous functional roles in plant growth and development, including cutin wax formation, pollen tube adhesion, cell expansion, seed development, germination, and adaptation to changing environmental conditions. LTPs contain eight conserved cysteine residues and a hydrophobic cavity that provides a wide variety of lipid-binding specificities. As members of the pathogenesis-related protein 14 family (PR14), many LTPs inhibit fungal or bacterial growth, and act as positive regulators in plant disease resistance. Over the past decade, these essential immunity-related roles of LTPs in plant immune processes have been documented in a growing body of literature. In this review, we summarize the roles of LTPs in plant-pathogen interactions, emphasizing the underlying molecular mechanisms in plant immune responses and specific LTP functions.


Assuntos
Cisteína , Proteínas de Plantas , Proteínas de Plantas/química , Desenvolvimento Vegetal , Sementes/metabolismo , Plantas/metabolismo , Lipídeos
8.
Artigo em Inglês | MEDLINE | ID: mdl-35742697

RESUMO

This study aims to analyze the spatiotemporal distribution and evolution of digestive tract cancer (DTC) in Lujiang County, China by using the geographic information system technology. Results of this study are expected to provide a scientific basis for effective prevention and control of DTC. The data on DTC cases in Lujiang County, China, were downloaded from the Data Center of the Center for Disease Control and Prevention in Hefei, Anhui Province, China, while the demographic data were sourced from the demographic department in China. Systematic statistical analyses, including the spatial empirical Bayes smoothing, spatial autocorrelation, hotspot statistics, and Kulldorff's retrospective space-time scan, were used to identify the spatial and spatiotemporal clusters of DTC. GM(1,1) and standard deviation ellipses were then applied to predict the future evolution of the spatial pattern of the DTC cases in Lujiang County. The results showed that DTC in Lujiang County had obvious spatiotemporal clustering. The spatial distribution of DTC cases increases gradually from east to west in the county in a stepwise pattern. The peak of DTC cases occurred in 2012-2013, and the high-case spatial clusters were located mainly in the northwest of Lujiang County. At the 99% confidence interval, two spatiotemporal clusters were identified. From 2012 to 2017, the cases of DTC in Lujiang County gradually shifted to the high-incidence area in the northwest, and the spatial distribution range experienced a process of "dispersion-clustering". The cases of DTC in Lujiang County will continue to move to the northwest from 2018 to 2025, and the predicted spatial clustering tends to be more obvious.


Assuntos
Neoplasias , Teorema de Bayes , China/epidemiologia , Análise por Conglomerados , Trato Gastrointestinal , Humanos , Incidência , Estudos Retrospectivos , Análise Espaço-Temporal
9.
Biomed Opt Express ; 13(1): 222-236, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35154866

RESUMO

The diagnosis and treatment of glioma depends greatly on the rapid extraction of molecular pathological features. In this study, human brain tumor tissues of different grades were analyzed using terahertz (THz) attenuated total reflectance (ATR) time-domain spectroscopy. Substantial differences in THz parameters were observed between paracarcinoma tissue and grade I-IV gliomas, Furthermore, the difference of THz absorption coefficient increases with the increase of THz frequency. It was also demonstrated that the isocitrate dehydrogenase (IDH) mutant and wild-type glioma tissues can be well distinguished using THz spectroscopy. Therefore, THz ATR spectroscopy can realize molecular typing recognition based on molecular pathology. This will provide a theoretical basis for developing intraoperative real-time glioma recognition and diagnosis technology.

10.
Front Neurol ; 13: 1046441, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36845225

RESUMO

Myxoma is the most common type of benign cardiac tumor in adults, and it has a strong tendency to embolize or metastasize to distant organs. Patients with multiple brain metastases have rarely been seen in clinics; hence, standard treatment protocols for multimyxoma metastasis in the brain have not been established. We present the case of a 47-year-old female who had convulsions in the right hand and repeated seizures. Computed tomography revealed multiple tumor sites in her brain. Craniotomy was conducted to remove the tumor sites. However, recurrent brain tumors and unexpected cerebral infarctions occurred frequently shortly after the treatment because the cardiac myxoma had not been treated due to the patient's personal concerns. The myxoma was resected by gamma knife radiosurgery, and temozolomide was given prior to cardiac surgery. There has been no evidence of tumor recurrence from the 2 years following the surgery until the present. This case highlights the importance of prioritizing cardiac lesions over cerebral lesions; if a cerebral metastasis has been found, it is likely that the cardiac myxoma is already unstable, with high rates of spread and metastasis. Therefore, it is unwise to treat metastasis sites before the cardiac myxoma. Additionally, the case suggests that gamma knife radiosurgery combined with temozolomide is effective as treatment for multiple myxoma metastasis in the brain. Compared with conventional cerebral surgery, gamma knife radiosurgery is safer, causes less bleeding, and requires a shorter time for recovery.

11.
Mol Plant Pathol ; 23(6): 760-771, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873812

RESUMO

Extracellular vesicles (EVs) are rounded vesicles enclosed by a lipid bilayer membrane, released by eukaryotic cells and by bacteria. They carry various types of bioactive substances, including nucleic acids, proteins, and lipids. Depending on their cargo, EVs have a variety of well-studied functions in mammalian systems, including cell-to-cell communication, cancer progression, and pathogenesis. In contrast, EVs in plant cells (which have rigid walls) have received very little research attention for many decades. Increasing evidence during the past decade indicates that both plant cells and plant pathogens are able to produce and secrete EVs, and that such EVs play key roles in plant-pathogen interactions. Plant EVs contains small RNAs (sRNAs) and defence-related proteins, and may be taken up by pathogenic fungi, resulting in reduced virulence. On the other hand, EVs released by gram-negative bacteria contain a wide variety of effectors and small molecules capable of activating plant immune responses via pattern-recognition receptor- and BRI1-ASSOCIATED RECEPTOR KINASE- and SUPPRESSOR OF BIR1-mediated signalling pathways, and salicylic acid-dependent and -independent processes. The roles of EVs in plant-pathogen interactions are summarized in this review, with emphasis on important molecules (sRNAs, proteins) present in plant EVs.


Assuntos
Vesículas Extracelulares , Animais , Vesículas Extracelulares/metabolismo , Fungos , Mamíferos , Plantas , Transdução de Sinais , Virulência
12.
Shanghai Kou Qiang Yi Xue ; 30(5): 477-480, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34888598

RESUMO

PURPOSE: To investigate the effect of paired related homeobox1 (PRRX1) on autophagy of salivary adenoidcystic carcinoma (SACC) cells. METHODS: PRRX1-overexpressed lentiviral vectors and their negative control lentiviral vectors were used to transfect SACC cells. The transfection effect was detected by Western blot. Autophagosome was observed under transmission electron microscopy(TEM). The level of autophagy markers (LC3-II/Beclin1) was detected by immunofluorescence and Western blot. Statistical analysis was performed with SPSS 17.0 software package. RESULTS: PRRX1 protein level increased, autophagosome number decreased, and autophagy marker level decreased in the PRRX1 overexpressed group, compared to the control (P<0.05). CONCLUSIONS: PRRX1 inhibits the autophagy of SACC cells.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Autofagia , Proteína Beclina-1 , Carcinoma Adenoide Cístico/genética , Linhagem Celular Tumoral , Proteínas de Homeodomínio , Humanos , Neoplasias das Glândulas Salivares/genética
13.
Int J Biol Macromol ; 193(Pt B): 1457-1470, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34742844

RESUMO

Demyelination is observed in animal models of intractable epilepsy (IE). Epileptogenesis damages the myelin sheath and dysregulates oligodendrocyte precursor cell (OPC) development. However, the molecular pathways regulating demyelination in epilepsy are unclear. Here, we predicted the molecular mechanisms regulating demyelination in a rat model of lithium-pilocarpine hydrochloride-induced epilepsy. We identified DGKA/Mboat2/Inpp5j and NOS/Keratin 28 as the main target molecules that regulate demyelination via glycerolipid and glycerophospholipid metabolism, phosphatidylinositol signaling, and estrogen signaling in demyelinated forebrain slice cultures (FSCs). In seizure-like FCSs, the actin cytoskeleton was regulated by Cnp and MBP via Pak4/Tmsb4x (also known as Tß4) and Kif5c/Kntc1. Tß4 possibly prevented OPC differentiation and maturation and inhibited MBP phosphorylation via the p38MAPK/ERK1/JNK1 pathway. The MAPK signaling pathway was more likely activated in seizure-like FCSs than in demyelinated FCSs. pMBP expression was decreased in the hippocampus of lithium-pilocarpine hydrochloride-induced acute epilepsy rats. The expression of remyelination-related factors was suppressed in the hippocampus and corpus callosum in lithium-pilocarpine hydrochloride-induced epilepsy rats. These findings suggest that the actin cytoskeleton, Tß4, and MAPK signaling pathways regulate the decrease in pMBP in the hippocampus in a rat model of epilepsy. Our results indicate that regulating the actin cytoskeleton, Tß4, and MAPK signaling pathways may facilitate the prevention of demyelination in IE.


Assuntos
Doenças Desmielinizantes/metabolismo , Epilepsia/induzido quimicamente , Epilepsia/metabolismo , Lítio/farmacologia , Pilocarpina/farmacologia , Transdução de Sinais/fisiologia , Animais , Diferenciação Celular/efeitos dos fármacos , Doenças Desmielinizantes/induzido quimicamente , Modelos Animais de Doenças , Hipocampo/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Proteômica/métodos , Ratos , Ratos Sprague-Dawley , Timosina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Front Oncol ; 11: 757650, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796112

RESUMO

Long non-coding RNAs (lncRNAs) serve essential roles on various biological functions. Previous studies have indicated that lncRNAs are involved in the occurrence, growth and infiltration of brain tumors. LncRNA H19 is key regulator in the pathogenesis of gliomas, but the underlying mechanisms of H19-regulated tumor progression remain unknown. Therefore, we investigated the effects and mechanism of action of lncRNA H19 on the homeostasis of glioma cells. As a novel oncogenic factor, up-regulation of H19 was able to promote the proliferation of glioma cells by targeting miR-200a. Furthermore, elevated miR-200a levels could reverse H19-induced cell growth and metastasis. Overexpression of miR-200a could significantly suppress the proliferation, migration and invasion of glioma cells. These biological behavior changes in glioma cells were dependent on the binding to potential target genes including CDK6 and ZEB1. CDK6 could promote cell proliferation and its expression was remarkably increased in glioma. In addition, up-regulation of miR-200a lead to reduction of CDK6 expression and inhibit the proliferation of glioma cells. ZEB1 could be a putative target gene of miR-200a in glioma cells. Thus, miR-200a might suppress cell invasion and migration through down-regulating ZEB1. Moreover, overexpression of miR-200a resulted in down-regulation of ZEB1 and further inhibited malignant phenotype of glioma cells. In summary, our findings suggested that the expression of H19 was elevated in glioma, which could promote the growth, invasion and migration of tumor cells via H19/miR-200a/CDK6/ZEB1 axis. This novel signaling pathway may be a promising candidate for the diagnosis and targeted treatment of glioma.

15.
J Mater Chem B ; 9(32): 6387-6395, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34309613

RESUMO

The great interest in using nanoparticles (NPs) for biomedical applications is transversal to various materials despite the poorly understood correlation between their physicochemical properties and effects on the immune system. NPs, such as gold and Fe3O4, are generally regarded as safe, but the immunotoxicological profile of Au/Fe3O4 composite NPs with different physicochemical properties is not well documented. This study investigated the biological impact of Au/Fe3O4 composite NPs with different morphologies (spherical core-shell and flower-like) and shell composition in vitro to analyze their potential cytotoxic effects and inflammatory responses on RAW 264.7 cells. Au/Fe3O4 composite NPs with a flower-like structure (FLNPs) induce a pronounced reduction in cell viability compared with Au/Fe3O4 composite NPs with a spherical core-shell structure (CSNPs). The increased production of reactive oxygen species, which damages cellular membranes, might contribute to the cytotoxicity effect of FLNPs. However, CSNPs presented more RAW 264.7 cell adhesion and uptake than FLNPs. Remarkably, a significant TNF-α release was observed with CSNP treated RAW 264.7 cells other than that of FLNPs. Protein corona analysis revealed the adsorption of a distinct amount and profile of proteins on the surface of CSNPs and FLNPs. Given the similar particle size and ζ-potential of CSNPs and FLNPs under the cell culture condition, results indicate that the impact of Au/Fe3O4 composite NPs on the macrophage activity highly depends on their morphology, shell composition and protein corona profile.


Assuntos
Compostos Férricos/química , Ouro/química , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Coroa de Proteína/química , Animais , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/metabolismo , Camundongos , Células RAW 264.7
16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(1): 106-112, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-34117854

RESUMO

:To investigate the effect of transient receptor potential melastatin 2 (TRPM2) inhibitor A10 on oxygen glucose deprivation/reperfusion (OGD/R) injury in SH-SY5Y cells.:Human neuroblastoma SH-SY5Y cells were subject to OGD/R injury,and then were divided into blank control group,model control group and A10 group randomly. The cell survival rate was detected by cell counting kit 8 (CCK-8); the level of cellular reactive oxygen species (ROS) was detected by reactive oxygen detection kit; the mitochondrial membrane potential was detected by tetramethylrhodamine (TMRM) method; the number of apoptotic cells was detected by TUNEL apoptosis assay kit; the protein expression level of cleaved caspase 3 was detected by Western blot.:Compared with 3,20,30,50, has lower cytotoxicity and better inhibition effect on channel activity. Compared with the model control group,ROS level was reduced,the mitochondrial membrane potential was improved,the number of apoptosis cells was reduced ,and the expression of cleaved caspase 3 was significantly reduced in the A10 group(all <0.05). : A10 can alleviate cell damage after OGD/R by inhibiting TRPM2 channel function,reducing extracellular calcium influx,reducing cell ROS levels,stabilizing mitochondrial membrane potential levels,and reducing apoptosis.


Assuntos
Glucose , Canais de Cátion TRPM , Apoptose , Benzenoacetamidas , Sobrevivência Celular , Humanos , Oxigênio/metabolismo , Piperidonas , Espécies Reativas de Oxigênio/metabolismo , Reperfusão
17.
Anticancer Drugs ; 32(9): 930-938, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34016833

RESUMO

Hesperetin is an abundant flavonoid in citrus fruits, and be confirmed to possess a chemo-preventive effect on cancer. Migration and invasion are the main causes of death of cervical cancer patients, in which epithelial-mesenchymal transition (EMT) can directly contribute to malignant phenotypes of tumor cells. The present study aims to investigate the inhibitory effect of hesperetin on EMT-mediated invasion and migration in cervical cancer cells through transforming growth factor-ß1 (TGF-ß1)/Smads pathway. Cell viability, cell migration and invasion ability, and cell morphology were evaluated and monitored using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays, Transwell assays and optical microscope, respectively. The change of EMT marker protein E-cadherin and N-cadherin was assessed by immunofluorescence assay, whereas the protein expression of EMT bio-marker and TGF-ß1/Smads pathway were detected through western blot analysis. In conclusion, hesperetin can suppress EMT-mediated invasion and migration of cervical cancer cells by inhibiting abnormal activation of TGF-ß1/Smads pathway. The study provides an experimental basis for the prevention of the invasion and migration of cervical cancer.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Hesperidina/farmacologia , Proteínas Smad/efeitos dos fármacos , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Neoplasias do Colo do Útero/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Transdução de Sinais/efeitos dos fármacos
18.
Analyst ; 146(12): 4080-4086, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34052846

RESUMO

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has been widely applied for the analysis of large biomolecules. The emergence of inorganic material substrates and new organic matrices extends the use of MALDI MS for small molecule analyses. However, there are usually preferred matrices for different types of analytes. Here, an organic compound, 4-hydroxy-3-nitrobenzonitrile, was found to be a general purpose matrix for the analyses of small organic, peptide and protein molecules. In particular, 4-hydroxy-3-nitrobenzonitrile has a strong UV absorption property, and it provides a clean background in the low mass range. Its analytical performances as a UV-laser matrix were demonstrated for different types of analytes, including organic drugs, peptides, proteins, mouse brain tissue and bacteria. Compared with commercial matrices, this new matrix has better performances when analyzing small molecules, such as drugs, peptides and lipids, while it has similar performances when analyzing proteins.


Assuntos
Peptídeos , Proteínas , Animais , Lipídeos , Camundongos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
19.
Insects ; 12(5)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919000

RESUMO

Aphids transmit CMV (cucumber mosaic virus) in a non-persistent manner. However, little is known about the mechanism of CMV transmission. In this study, an integrated analysis of the mRNA and protein was performed to identify important putative regulators involved in the transmission of CMV by aphids. At the level of transcription, a total of 20,550 genes (≥2-fold expression difference) were identified as being differentially expressed genes (DEGs) 24 h after healthy aphid transfer to infected tobacco plants using the RNA-seq approach. At the protein level, 744 proteins were classified as being differentially abundant between virus-treated and control M. persicae using iTRAQ (isobaric tags for relative and absolute quantitation) analysis. The combined mRNA and protein analysis enabled the identification of some viral putative regulators, such as cuticle proteins, ribosomal proteins, and cytochrome P450 enzymes. The results show that most of the key putative regulators were highly accumulated at the protein level. Based on those findings, we can speculate that the process by which aphids spread CMV is mainly related to post-translational regulation rather than transcription.

20.
Analyst ; 146(7): 2248-2254, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33599220

RESUMO

Tumorigenesis driven by abnormal DNA methylation has highlighted the need to develop a portable, rapid and sensitive strategy for accurate methylation detection with a specific cancer-prognostic gene, which caters to the popularization of precision medicine. In this study, a site-specific biosensor for both visual and magnetic DNA methylation determination has been established based on lateral flow assay. By introducing digoxin- and biotin-labeled primers into PCR, the amplicons can be recognized and captured by gold magnetic nanoparticles (GMNPs) in this biosensor. Working as a signal probe, the optical property of GMNPs allows the amplicons to be interpreted with naked eyes avoiding any complex equipment and cumbersome operation after PCR. Moreover, by virtue of the magnetic property of GMNP, the signal can be explained and recorded by a magnetometer in clinical practice. The introduction of tailor-made primer sets makes it possible to accurately distinguish 0.1% methylated variants in the presence of numerous unmethylated variants as strong interferential background and vice versa at target cytosine-guanine dinucleotide. A distinct signal can be observed with as low as 0.01 pg variants for both visual and magnetic analyses. As a significant tumor suppressor gene, the promoter methylation status of miR-34a is accurately determined with not only cell lines but also with clinical samples, which demonstrates the great potential of this biosensor for cancer diagnosis and prognosis.


Assuntos
Técnicas Biossensoriais , Metilação de DNA , Ouro , Fenômenos Magnéticos , Reação em Cadeia da Polimerase
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA