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1.
Langmuir ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38920295

RESUMO

Pickering double emulsions exhibit higher stability and biocompatibility compared with surfactant-stabilized double emulsions. However, tailored synthesis of particle stabilizers with appropriate wettability is time consuming and complicated and usually limits their large-scale adoption. Using binary stabilizers may be a simple and scalable strategy for Pickering double emulsion formation. Herein, commercially available hydrophobic silica nanoparticles (SNPs) and sodium alginate (SA) as binary stabilizers are used to prepare O/W/O Pickering double emulsions in one-step emulsification. The influence of system composition on double emulsion preparation is identified by optical microscopy, confocal laser scanning microscopy, and interfacial tension and water contact angle analyses. The formation of the O/W/O Pickering double emulsion depends critically on the aqueous phase viscosity and occurrence of emulsion inversion. Both hydrophobic SNPs and SA adsorb at the droplet surface to provide a steric barrier, while SA also reduces interfacial tension and increases aqueous phase viscosity, giving double emulsion long-term stability. Their microstructure and stability are controlled by adjusting the SA concentration, water-oil volume ratio, concentration and wettability of the particle stabilizer, and oil type. As a demonstration, the middle layer of the as-prepared O/W/O Pickering double emulsions can be cross-linked in situ with calcium ions to produce calcium alginate porous microspheres. We believe that our strategy for double emulsion formation holds great potential for practical applications in food, cosmetics, or pharmaceuticals.

2.
RSC Adv ; 14(28): 20130-20144, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38915333

RESUMO

Multidrug-resistant bacteria resulting from the abuse and overuse of antibiotics have become a huge crisis in global public health security. Therefore, it is urgently needed to develop new antibacterial drugs with unique mechanisms of action. As a versatile moiety, morpholine has been widely employed to enhance the potency of numerous bioactive molecules. In this study, a series of ruthenium-based antibacterial agents modified with the morpholine moiety were designed and characterized, aiming to obtain a promising metalloantibiotic with a multitarget mechanism. Antibacterial activity screening demonstrated that the most active complex Ru(ii)-3 exhibited the strongest potency against Staphylococcus aureus (S. aureus) with an MIC value of only 0.78 µg mL-1, which is better than most clinically used antibiotics. Notably, Ru(ii)-3 not only possessed excellent bactericidal efficacy, but could also overcome bacterial resistance. Importantly, Ru(ii)-3 very efficiently removed biofilms produced by bacteria, inhibited the secretion of bacterial exotoxins, and enhanced the activity of many existing antibiotics. The results of mechanism studies confirmed that Ru(ii)-3 could destroy the bacterial membrane and induce ROS production in bacteria. Furthermore, animal infection models confirmed that Ru(ii)-3 showed significant anti-infective activity in vivo. Overall, this work demonstrated that a morpholine-modified ruthenium-based agent is a promising antibiotic candidate in tackling the crisis of drug-resistant bacteria.

3.
RSC Adv ; 14(23): 16194-16206, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38769952

RESUMO

The rapid emergence and spread of multidrug-resistant bacteria pose a serious challenge to human life and health, necessitating the development of novel antibacterial agents. Herein, to address this challenge, three iridium-based antibacterial agents were prepared and their antimicrobial activity were explored. Importantly, the three complexes all showed robust potency against S. aureus with MIC values in the range of 1.9-7.9 µg mL-1. Notably, the most active complex Ir3 also exhibited relative stability in mammalian fluids and a significant antibacterial effect on clinically isolated drug-resistant bacteria. Mechanism studies further demonstrated that the complex Ir3 can kill S. aureus by disrupting the integrity of the bacterial membrane and inducing ROS production. This multi-target advantage allows Ir3 to not only effectively combat bacterial resistance but also efficiently clear the bacterial biofilm. In addition, when used together, complex Ir3 could enhance the antibacterial potency of some clinical antibiotics against S. aureus. Moreover, both G. mellonella wax worms and mouse infection model demonstrated that Ir3 has low toxicity and robust anti-infective efficacy in vivo. Overall, complex Ir3 can serve as a new antibacterial agent for combating Gram-positive bacterial infections.

4.
Gels ; 10(5)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38786252

RESUMO

Herein, the starch nanocrystal/tannic acid (ST) complex particles, which were prepared based on the hydrogen bond between starch nanocrystal (SNC) and tannic acid (TA), were successfully used to stabilize the HIPPE gels. The optimal TA concentration of the ST complex particles resulted in better water dispersibility, surface wettability, and interfacial activity as compared to SNC. The hydrogen bond responsible for the formation of ST complex particles and subsequent stable emulsions was demonstrated by varying the pH and ionic strength of the aqueous phase. Notably, the HIPPE gels stabilized via the ST complex particles can maintain long-term stability for up to three months. The HIPPEs stabilized via the ST complex particles all displayed gel-like features and had smaller droplets and denser droplet networks than the SNC-stabilized HIPPEs. The rheological behavior of HIPPE gels stabilized via the ST complex particles can be readily changed by tuning the mass ratio of SNC and TA as well as pH. Finally, the prepared HIPPE gels used to effectively protect encapsulated ß-carotene against high temperatures and ultraviolet radiation and its controllable release at room temperature were demonstrated. It is anticipated that the aforementioned findings will provide new perspectives on the preparation of Pickering emulsion for delivery systems.

5.
Polymers (Basel) ; 16(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38475375

RESUMO

A dual biofunctional hydrogel (HQCS-SP) wound dressing, offering antibacterial properties and a biological response, was innovatively designed and developed to repair full-layer skin defects. The HQCS-SP hydrogel creates an artificial matrix that facilitates cell recruitment, extracellular matrix deposition, exhibiting exceptional tissue affinity, robust self-healing, effective hemostatic capabilities and accelerates wound healing. It is synthesized by crosslinking modified chitosan (HQCS) with spirulina protein (SP) and Fe3+. The HQCS provides antibacterial, antioxidant, good tissue affinity and excellent hemostasis performance. The incorporation of SP not only reinforces the antioxidant, antibacterial, anti-inflammatory, and pro-angiogenesis effects but also participates in the regulation of signal pathways and promotes wound healing. Therefore, this study offers a new visual angle for the design of advanced functional trauma dressings with great application potential in the bio-medical field.

6.
Nat Commun ; 15(1): 1986, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443343

RESUMO

What is static charge? Despite the long history of research, the identity of static charge and mechanism by which static is generated by contact electrification are still unknown. Investigations are challenging due to the complexity of surfaces. This study involves the molecular-scale analysis of contact electrification using highly well-defined surfaces functionalized with a self-assembled monolayer of alkylsilanes. Analyses show the elementary molecular steps of contact electrification: the exact location of heterolytic cleavage of covalent bonds (i.e., Si-C bond), exact charged species generated (i.e., alkyl carbocation), and transfer of molecular fragments. The strong correlation between charge generation and molecular fragments due to their signature odd-even effects further shows that contact electrification is based on cleavage of covalent bonds and transfer of ionic molecular fragments. Static charge is thus an alkyl carbocation; in general, it is an ionic molecular fragment. This mechanism based on cleavage of covalent bonds is applicable to general types of insulating materials, such as covalently bonded polymers. The odd-even effect of charging caused by the difference of only one atom explains the highly sensitive nature of contact electrification.

7.
J Gastrointest Surg ; 27(12): 2787-2796, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37932596

RESUMO

BACKGROUND: Tumor morphology links to early recurrence of hepatocellular carcinoma. Controversy exists regarding the recurrence risk of Liver Imaging Reporting and Data System morphologic Type II hepatocellular carcinoma. This study aims to explore risk factors for early recurrence of Type II hepatocellular carcinoma. METHODS: Retrospective analysis of hepatocellular carcinoma patients who underwent curative resection and preoperative contrast-enhanced MRI from June 2016 to June 2020. Our patients formed the development set, and hepatocellular carcinoma patients from the TCIA database served as validation. Univariable and multivariable Cox regression identified independent risk factors for early recurrence. A risk scoring system was established for risk stratification, and an early recurrence prediction model was developed and validated. RESULTS: 95 Type II hepatocellular carcinoma patients were in the development set, and 29 cases were in the validation set. Early recurrence rates were 33.7% and 37.9%, respectively. Multivariate analysis revealed age, histological grade, AFP, and intratumoral hemorrhage as independent risk factors for early recurrence. The model's diagnostic performance for early recurrence was AUC = 0.817 in the development set. A scoring system classified patients into low-risk (scores ≤ 3) and high-risk (scores > 3) groups. The high-risk group had significantly lower recurrence-free survival (40.0% vs 73.2%, P = 0.001), consistent with the validation set (25.0% vs 73.3%, P = 0.028). CONCLUSIONS: The risk scoring system demonstrated excellent discrimination and predictive ability, aiding clinicians in assessing early recurrence risk and identifying high-risk individuals effectively.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Fatores de Risco , Imageamento por Ressonância Magnética
8.
Ann Clin Lab Sci ; 53(5): 719-725, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37945010

RESUMO

OBJECTIVE: To investigate the expression of lncRNA UCA1 in serum of patients with acute cerebral infarction (ACI) and its relationship with prognosis. METHODS: The serum lncRNA UCA1 level in participants was detected, and the correlation between the neurological function score (NIHSS score) of ACI patients and lncRNA UCA1 expression was analyzed. Patients were followed up at 3 months after discharge and were divided into favorable and unfavorable prognostic groups according to the modified Rankin scale (mRs). The risk factors of ACI patients with poor prognosis were analyzed, and the predictive value of each index for ACI prognosis was evaluated by ROC curve. RESULTS: The level of lncRNA UCA1 in ACI group was increased (P<0.001). ROC analysis showed that high lncRNA UCA1 expression had clinical significance for the diagnosis of ACI. Spearman correlation analysis revealed that NIHSS score was positively correlated with lncRNA UCA1 expression level in ACI group (r=0.6537, P<0.001). Hcy level and NIHSS score in poor prognosis group (n=63) were higher than those in good prognosis group (n=84), and lncRNA UCA1 level in serum in poor prognosis group was increased in comparison to good prognosis group (P<0.05). Logistic regression analysis investigated that admission NIHSS score, infarct size, and increased lncRNA UCA1 were the risk factors affecting the prognosis of ACI. CONCLUSION: Serum lncRNA UCA1 is abnormally elevated in ACI patients, and the elevated lncRNA UCA1 not only shows high accuracy in the diagnosis of ACI, but also has a certain predictive value for poor prognosis of ACI.


Assuntos
Isquemia Encefálica , RNA Longo não Codificante , Acidente Vascular Cerebral , Humanos , Infarto Cerebral/genética , Infarto Cerebral/diagnóstico , Relevância Clínica , Prognóstico , RNA Longo não Codificante/genética
9.
Int J Geriatr Psychiatry ; 38(10): e6010, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37794769

RESUMO

OBJECTIVES: The proportion of older people with dementia in China is gradually increasing with the increase in the aging population over recent years. Hypertension and diabetes are common non-communicable diseases among rural populations in China. However, it remains unclear whether these conditions affect the occurrence and development of cognitive impairment as there is limited research on cognitive status and its risk factors among residents of rural areas. METHODS: A multi-stage stratified cluster random sampling method was used to select 5400 participants from rural permanent residents. A self-designed structured questionnaire was used to investigate demographic data of the participants. Cognitive function was assessed using the Montreal Cognitive Function Assessment Scale (MoCA). The results were analyzed using chi-square test, ANOVA and multiple linear regression analysis. RESULTS: A total of 5028 participants returned the survey, giving a response rate of 93.1%. Higher education (odds ratio (OR) = 3.2, 95% confidence interval (CI) 2.87-3.54, p < 0.001), higher income (OR = 1.61, 95% CI 1.16-2.07, p < 0.001), and dietary control (OR = 0.66, 95%CI 0.34-0.98, p < 0.001) were protective factors. A visual representation of the relationship between annual income and MoCA score showed an inverted U-curve, the group with an annual income of 6000-7999 RMB had a maximum OR of 1.93 (95%CI 0.12-2.74, p < 0.001). While difficulty in maintaining sleep were risk factors for cognitive impairment (OR = -2.28, 95% CI-4.18-0.39, p = 0.018). CONCLUSIONS: Participants with middle incomes had better cognitive status than those with the highest incomes. Higher education, proper diet control and good sleep are beneficial to the cognitive status of residents in rural areas.


Assuntos
Diabetes Mellitus , Hipertensão , Humanos , Idoso , Estudos Transversais , População Rural , Fatores de Risco , Hipertensão/epidemiologia , Cognição , China/epidemiologia
10.
Front Neurol ; 14: 1029370, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36970514

RESUMO

Objective: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are collectively known as Lewy body dementia (LBD). Considering the heterogeneous nature of LBD and the different constellations of symptoms with which patients can present, the exact molecular mechanism underlying the differences between these two isoforms is still unknown. Therefore, this study aimed to explore the biomarkers and potential mechanisms that distinguish between PDD and DLB. Methods: The mRNA expression profile dataset of GSE150696 was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between 12 DLB and 12 PDD were identified from Brodmann area 9 of human postmortem brains using GEO2R. A series of bioinformatics methods were applied to identify the potential signaling pathways involved, and a protein-protein interaction (PPI) network was constructed. Weighted gene co-expression network analysis (WGCNA) was used to further investigate the relationship between gene co-expression and different LBD subtypes. Hub genes that are strongly associated with PDD and DLB were obtained from the intersection of DEGs and selected modules by WGCNA. Results: A total of 1,864 DEGs between PDD and DLB were filtered by the online analysis tool GEO2R. We found that the most significant GO- and KEGG-enriched terms are involved in the establishment of the vesicle localization and pathways of neurodegeneration-multiple diseases. Glycerolipid metabolism and viral myocarditis were enriched in the PDD group. A B-cell receptor signaling pathway and one carbon pool by folate correlated with DLB in the results obtained from the GSEA. We found several clusters of co-expressed genes which we designated by colors in our WGCNA analysis. Furthermore, we identified seven upregulated genes, namely, SNAP25, GRIN2A, GABRG2, GABRA1, GRIA1, SLC17A6, and SYN1, which are significantly correlated with PDD. Conclusion: The seven hub genes and the signaling pathways we identified may be involved in the heterogeneous pathogenesis of PDD and DLB.

11.
J Cell Mol Med ; 26(23): 5820-5831, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36317420

RESUMO

Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis-related genes have prognostic predictive value has not been clarified. In this study, uni-/multi-variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis-related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high- and low-risk groups. Either for grade 2-3 or for grade 4, glioma patients with high-risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high-risk group was functionally associated with immune responses and cancer-related pathways. The high-risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high-risk group were significantly higher than those in the low-risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T-cell co-stimulation pathways. In conclusion, we established a risk model based on cuproptosis-related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno-microenvironment status of glioma.


Assuntos
Apoptose , Glioma , RNA Longo não Codificante , Humanos , Glioma/genética , Glioma/terapia , Fatores Imunológicos , Imunoterapia , Nomogramas , RNA Longo não Codificante/genética , Cobre
12.
Medicine (Baltimore) ; 101(35): e30233, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107521

RESUMO

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma(SPTCL) is a very rare cytotoxic T-cell skin lymphoma involving subcutaneous tissue, and mainly affects young females. T-cell phenotype is characterized by CD3+, CD8+, and CD4-. SPTCT with polycranial neuropathy has rarely been described. SPTCL is believed to show an indolent clinical course unless patients develop haemophagocytic syndrome or sudden respiratory failure. Its treatment has not been established yet. CASE PRESENTATION: We report a case of intractable SPTCT in a 66-year-old woman with multiple cranial nerve palsies and diabetes. She showed involvement of the bilateral facial nerve, left trigeminal nerve, left auditory nerve, and right oculomotor nerve. The single inconspicuous skin lesion in the trunk presented with an erythematous nodule with a diameter of <5 cm and a slightly pink infiltrated plaque. Electromyography revealed bilateral damage to the facial nerve. Differential immunohistochemical characteristics were observed. Immunohistochemistry demonstrated diffuse CD20 positivity. Cerebral spinal fluid analysis revealed elevated protein levels of 0.92 (0.15-0.45) g/L. Her condition regressed severely over time. She was treated with chemotherapy but died 10 months later, the probable cause of death was lung involvement. CONCLUSION: The patient's involvement with the central nervous system may be associated with positivity for CD20. Molecular biomarkers may act as therapeutic targets for SPTCL.


Assuntos
Linfoma Cutâneo de Células T , Linfoma de Células T , Paniculite , Doenças do Sistema Nervoso Periférico , Neoplasias Cutâneas , Feminino , Humanos , Linfoma de Células T/complicações , Linfoma de Células T/diagnóstico , Linfoma de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/tratamento farmacológico , Paniculite/diagnóstico , Paniculite/tratamento farmacológico , Paniculite/etiologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Neoplasias Cutâneas/patologia
13.
Nucl Med Commun ; 43(2): 177-185, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34864810

RESUMO

OBJECTIVE: To develop an 18F-fluorodeoxyglucose PET/computed tomography (CT) scoring model based on metabolic and radiologic findings of the pleura and fluid to identify malignant pleural effusion. METHODS: The PET and CT findings from patients with pleural effusion in the derivation dataset were used to develop a scoring model. Then, the diagnostic accuracy of the predictive score was verified by the validation dataset. RESULTS: Eight parameters independently predicting malignancy were retained in the scoring model, including pleural nodules or masses (4 points), focal pleural thickening (2 points), absence of pleural loculation (2 points), thickness of mediastinal pleura involvement ≥0.5 cm (2 points), maximum standardized uptake value (SUVmax) of mediastinal pleura involvement ≥2.3 (2 points), thickness of nonmediastinal pleura involvement ≥0.5 cm (1 point), SUVmax of nonmediastinal pleura involvement ≥3.0 (1 point) and fluid SUVmax ≥1.6 (1 point). The operating characteristics of the PET/CT score were 0.958 area under the curve (AUC), 88.6% sensitivity, 91.2% specificity, 10.09 positive likelihood ratio and 0.13 negative likelihood ratio, with 6 points as the threshold. These values in the validation dataset were 0.947, 91.7%, 88.4%, 7.91 and 0.094, respectively. No difference was found in AUCs between the derivation and validation datasets (z = 0.517, P = 0.697). The negative predictive value was 99.4% in the score from 0 to 2, and the positive predictive value was 98.3% for patients with score between 9 and 15. CONCLUSIONS: The PET/CT scoring model is a valuable strategy to help physicians to distinguish malignant-benign pleural effusion and stratify patients who will benefit from invasive procedures.


Assuntos
Fluordesoxiglucose F18
14.
Front Oncol ; 11: 764189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956885

RESUMO

BACKGROUND: Precise evaluation of the efficacy of immunotherapy is critical in the effective management and treatment of advanced hepatocellular carcinoma (HCC). Therefore, the purpose of this study was to compare the response assessments achieved by different criteria and to evaluate the correlation between survival outcome and response assessment in HCC treated with programmed cell death protein 1 (PD-1) inhibitor. METHODS: Fifty patients with advanced HCC treated with first-line PD-1 inhibitor with baseline and follow-up CT images were analyzed. The patients were categorized into responders and nonresponders according to the criteria. RESULTS: When the response assessments between RECIST 1.1 and mRECIST were compared, no statistically significant differences were observed. Overall response rate was 16% by RECIST 1.1 and iRECIST and was 24% by mRECIST. According to RECIST 1.1 and mRECIST, overall survival (OS) and progression-free survival (PFS) were not statistically different between the complete response (CR) and partial response (PR) groups and the stable disease (SD) and progressive disease (PD) groups. The OS and PFS were significantly different between responders and nonresponders according to mRECIST. The Cohen's Kappa for RECIST 1.1, iRECIST, and mRECIST was 0.534, 0.438, and 0.363, respectively. CONCLUSION: The mRECIST criteria have a powerful ability to discriminate between responders and nonresponders and demonstrated significantly longer OS and PFS in responders than in nonresponders. However, mRECIST needs to be further improved in order for it to be widely used in the clinical evaluation of immunotherapy in HCC.

15.
Crit Rev Eukaryot Gene Expr ; 31(5): 33-40, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34591388

RESUMO

The microRNA MiR-24-3p suppresses cancer progression by targeting TRIM11. The long noncoding RNA LUADT1 has been reported to promote lung adenocarcinoma proliferation. We found LUADT1 may form base pairing with miR-24-3p. This study aimed to explore the interactions among LUADT1, miR-24-3p, and TRIM11 in mantle cell lymphoma (MCL). Our study recruited 40 MCL patients and 40 healthy volunteers. Tumor tissues were collected from 40 newly diagnosed MCL patients and embedded in paraffin wax. B lymphocytes were isolated from all tissue samples by using CD19+ magnetic beads and DETACHaBEAD CD19. Human MCL cell line Grante-519 and JeKo-1 were transfected with LUADT1 and TRIM11 expression vectors, microRNA mimics or inhibitors. Then, quantitative polymerase chain reaction and Western blot were used to detect the level of relative messenger RNA and protein expression, respectively. Flow cytometry was performed to detect the apoptosis rate. LUADT1 and miR-24-3p were upregulated while TRIM11 was downregulated in MCL both in tissues and cell lines compared with hyperplastic lymphadenitis and peripheral lymphocyte cells. Bioinformatics analysis showed that LUADT1 may bind miR-24-3p, which can target TRIM11. Correlation analysis showed that LUADT1 was not significantly correlated with miR-24-3p. However, it was positively and significantly correlated with TRIM11. In MCL cells, LUADT1 overexpression led to upregulated TRIM11, whereas miR-24-3p overexpression led to downregulated TRIM11. Cell apoptosis analysis showed that LU-ADT1, miR-24-3p inhibitor and TRIM11 overexpression led to decreased apoptotic rate of MCL cells, whereas miR-24-3p overexpression led to an increased apoptotic rate of MCL cells. In addition, miR-24-3p overexpression attenuated the effects of LUADT1 overexpression. Therefore, LUADT1 was upregulated in MCL and could modulate TRIM11 by sponging miR-24-3p to inhibit cancer cell apoptosis.


Assuntos
Apoptose , Linfócitos B/metabolismo , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genética
16.
Exp Hematol ; 103: 52-59.e2, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34474146

RESUMO

Since the use of Bruton's tyrosine kinase (BTK) inhibitor ibrutinib in relapsed/refractory (R/R) mantle cell lymphoma (MCL), the problem of drug resistance has become increasingly prominent. Though it has been proven that the nonclassic nuclear factor κB pathway (nonclassic NF-κB pathway) correlates with ibrutinib resistance in MCL, the upstream regulator is unknown. In the present study, conserved helix-loop-helix ubiquitous kinase (CHUK) overexpression accelerated proliferation and suppressed apoptosis of MCL cells after ibrutinib treatment in vitro. The results of luciferase reporter assay, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blot revealed that CHUK was targeted and negatively regulated by miRNA-223-3p. miRNA-223-3p knockdown promoted proliferation and inhibited apoptosis of MCL cells after ibrutinib treatment in vitro and vivo, whereas CHUK knockdown reversed downregulated miRNA-223-3p-promoted cell proliferation after ibrutinib treatment in vitro. In conclusion, miRNA-223-3p modulates ibrutinib resistance through regulation of the CHUK/NF-κB signaling pathway in MCL, which is crucial in providing a marker to predict disease response.


Assuntos
Adenina/análogos & derivados , Linfoma de Célula do Manto/tratamento farmacológico , MicroRNAs/genética , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Adenina/farmacologia , Adenina/uso terapêutico , Animais , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Quinase I-kappa B/metabolismo , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia
17.
Onco Targets Ther ; 14: 1553-1564, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688203

RESUMO

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive malignancy that accounts for 5-10% of non-Hodgkin's lymphoma. MiRNA-223-3p has been demonstrated to be down-regulated in MCL and is a useful prognostic factor. However, little is known about underlying molecular mechanism of miRNA-233-3p in MCL. METHODS: The expression levels of miRNA-223-3p and CHUK mRNA in MCL cells were detected by real-time quantitative PCR (RT-qPCR). The effects of miRNA-223-3p/CHUK overexpression/knockdown on MCL cell proliferation and apoptosis were measured by CCK-8 assay and annexin V PE/7-AAD-based flow cytometry/TUNEL assay, respectively. A nude mouse subcutaneous xenograft model was used to further evaluate the potential effects in vivo. Dual-luciferase reporter assay was used to verify the inhibitory effect of miRNA-223-3p on CHUK. Furthermore, the regulatory function of miRNA-223-3p on the CHUK/NF-ƘB2 axis was assessed by RT-qPCR, western blot and immunofluorescence. RESULTS: In the present study, miRNA-223-3p overexpression inhibited proliferation and accelerated apoptosis of MCL cells in vitro and in vivo. The results of Luciferase reporter assay showed that CHUK was a direct target of miRNA-223-3p in HEK293T cells. Furthermore, the results of RT-qPCR, western blot confirmed that CHUK was targeted and negatively regulated by miRNA-223-3p for repressing NF-ƘB2 pathway activation in MCL cells. Importantly, CHUK overexpression promoted proliferation and suppressed apoptosis of MCL cells, whereas CHUK knockdown reversed down-regulated miRNA-223-3p -accelerated cell proliferation in vitro. CONCLUSION: In conclusion, miRNA-223-3p affects MCL development by regulating the CHUK/NF-ƘB2 signaling pathway, which is crucial to provide a novel therapeutic strategy.

18.
Int J Pharm ; 598: 120370, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577911

RESUMO

Medicine should ideally be personalized as each individual has his/her own unique biological, physical, and medical dispositions. Medicine can be personalized by customizing drug tablets with the specific drug dosages, release durations, and combinations of multiple drugs. This study presents a method for fabricating drug tablets with customizable dosages, durations, and combinations of multiple drugs by using the 3D printing technology. The method focuses on fabricating customizable drug tablets with a very simple structure for delivering the constant release profile due to its importance in treatment (i.e., the drug may produce side effects if too much is released andmay not have therapeutic value is too little is released). The method is simple: it involves first printing a template using the 3D printer and fabricating the drug tablet via the template. The tablets are customized by varying the amount of excipient used, the height of the tablet, and the numberand amount of drugs used. Three different common drugs (i.e., paracetamol, phenylephrine HCl and diphenhydramine HCl) and FDA-approved excipients are studied. The simplicity of the structure of the tablet and method via templating allows the fabrication of these fully customizable drug tablets to be easily performed, low-cost, efficient, and safe for consumption. These features enable the customizable tablets to be made widely accessible to the public; hence, the concept of personalized medicine can be realized.


Assuntos
Excipientes , Impressão Tridimensional , Acetaminofen , Liberação Controlada de Fármacos , Feminino , Humanos , Masculino , Medicina de Precisão , Comprimidos , Tecnologia Farmacêutica
19.
J Colloid Interface Sci ; 589: 378-387, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33482535

RESUMO

HYPOTHESIS: Highly hydrophilic nanoparticles are generally considered not suitable for stabilizing Pickering emulsions, since they could not be effectively wetted by the oil phase at the water-oil interface. However, highly hydrophilic nanoparticles with good dispersity are possibly absorbed and packed onto the surface of the oil droplets in water via the van der Waals attraction between the nanoparticles and the oil droplets. Hence, a novel "van der Waals emulsion" should be possible to be stabilized by highly hydrophilic nanoparticles. EXPERIMENTS: Oil-in-water emulsions solely stabilized by pristine TiO2 nanoparticles (i.e., TiO2 without any modification or additives) were prepared. The emulsification behavior under varying pH value, oil fraction, particle content and temperature of the emulsion were explored. Composite wax-based beads which encapsulated chemical sunscreen and was coated by TiO2 nanoparticles, was also fabricated using the obtained emulsion as the templates. FINDINGS: The emulsions displayed the highest stability near the isoelectric points of the TiO2 nanoparticles, which was attributed to the van der Waals attraction between TiO2 nanoparticles and oil droplets. Such mechanism was supported by a theoretical analysis based on calculation of the Hamaker constants and experimental evidences. Therefore, this work presents a simple, general and green method for preparing particle-stabilized emulsions.

20.
J Am Chem Soc ; 142(50): 21004-21016, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33284628

RESUMO

Aqueous liquids can be charged effectively by a number of methods for many important applications. Organic liquids, however, cannot be charged effectively by existing methods due to their low conductivities, especially the insulating nonpolar organic liquids; hence, there has not been any significant application developed based on charged organic liquids. This study describes an effective fundamental strategy for charging organic liquids, including nonpolar organic liquids: static charge is simply mixed into the liquid. Analyses suggested that the charged species are molecular ions that reside in the bulk of the liquid after charging. This method is simple and general, and the amount and polarity of charge can be flexibly tunable. The effectiveness of this method gives rise to opportunities for the development of novel applications. Charged organic droplets are manipulated for the first time by an electric field for controlling organic reactions. Particles with charge embedded in their bulk matrices are fabricated for the first time (i.e., via polymerizing the liquid monomers mixed with static charge). The charge in this novel class of bulk-charged particles is stable and permanent, especially when compared to the typical surface-charged particles. Simultaneous bulk-charged and bulk-magnetic particles are fabricated for the first time via simply mixing both the static charge and magnetic nanoparticles into the liquid monomers. These highly versatile particles are responsive to both electric and magnetic fields for practical applications.

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