Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.327
Filtrar
1.
Chemosphere ; 354: 141681, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38467199

RESUMO

Dimethylsilanediol (DMSD) is the common breakdown product of methylsiloxanes such as polydimethylsiloxane (PDMS) and volatile methylsiloxanes (VMS) in soil. In this work, we first present a sorbent selection experiment aiming to identify a sorbent that can trap gas-phase DMSD without causing DMSD condensation and VMS hydrolysis at environmentally relevant humidities. With a proper sorbent (Tenax) identified, the volatilization of DMSD from water and various wet soil and soil materials were measured in a controlled environment. It was demonstrated that DMSD underwent volatilization after soil water was completely evaporated. Various types of soil constituents show drastic differences in preventing DMSD from volatilization. Analysis of the sorbent-captured products provides further insight, most notably that virtually no cyclic methylsiloxanes are formed during the volatilization of DMSD from water or soil materials, except in one extreme case where only traces are detected.


Assuntos
Compostos de Organossilício , Solo , Água , Volatilização
2.
Int J Pharm ; 654: 123962, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38432450

RESUMO

The development of pediatric oral drugs is hampered by a lack of predictive simulation tools. These tools, in turn, require data on the physiological variables that influence oral drug absorption, including the expression of drug transporter proteins (DTPs) and drug-metabolizing enzymes (DMEs) in the intestinal tract. The expression of hepatic DTPs and DMEs shows age-related changes, but there are few data on protein levels in the intestine of children. In this study, tissue was collected from different regions of the small and large intestine from neonates (i.e., surgically removed tissue) and from pediatric patients (i.e., gastroscopic duodenal biopsies). The protein expression of clinically relevant DTPs and DMEs was determined using a targeted mass spectrometry approach. The regional distribution of DTPs and DMEs was similar to adults. Most DTPs, with the exception of MRP3, MCT1, and OCT3, and all DMEs showed the highest protein expression in the proximal small intestine. Several proteins (i.e., P-gp, ASBT, CYP3A4, CYP3A5, CYP2C9, CYP2C19, and UGT1A1) showed an increase with age. Such increase appeared to be even more pronounced for DMEs. This exploratory study highlights the developmental changes in DTPs and DMEs in the intestinal tract of the pediatric population. Additional evaluation of protein function in this population would elucidate the implications of the presented changes in protein expression on absorption of orally administered drugs in neonates and pediatric patients.


Assuntos
Proteínas de Transporte , Imidazóis , Proteínas de Membrana Transportadoras , Compostos de Organossilício , Adulto , Recém-Nascido , Humanos , Criança , Proteínas de Membrana Transportadoras/metabolismo , Intestino Delgado/metabolismo , Fígado/metabolismo
3.
ACS Sens ; 9(3): 1482-1488, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38416572

RESUMO

A pH colorimetric sensor array (CSA) was prepared on a nitrocellulose membrane and used for accurate pH measurement in highly concentrated saline solutions. The CSAs consisted of sensing spots made of a suitable OrMoSil polymer prepared from organo-fluorinated-silane precursors and/or organosilane with tetraethyl orthosilicate hosting an acid-base indicator. Four CSAs were prepared: D, 1F, 2F, and 3F. In D, a nonfluorinated organosilane was present. From 1F to 3F, the concentration of the fluorinated organosilane increased and improved the pH measurement accuracy in highly saline concentrations. No recalibrations were required, and the analytical signal was stable in time. D, 1F, 2F, and 3F were deposited in triplicate, and they were prepared to work in the seawater pH interval (7.50-8.50). The use of fluorinated precursors led to a lower pH prediction error and tailored the interval of the CSA at more basic pH values so that the inflection points of the sigmoidal calibrations of D, 1F, 2F, and 3F moved from 6.97 to 7.98. The overall pH prediction error was 0.10 pH (1F), 0.02 pH (2F), and 0.04 pH units (3F). The CSAs were stable, reversible, reusable, and independent of salinity (S) between 20 and 40. The performances of the CSA were compared with those of a glass electrode, whose pHNIST values were converted in the pHSWS scale through a conversion equation. Being unaffected by the typical drawback of the glass electrode, the CSAs can be used directly in seawater real samples, and it validated the proposed conversion equation.


Assuntos
Colorimetria , Compostos de Organossilício , Concentração de Íons de Hidrogênio , Água do Mar , Eletrodos , Solução Salina
4.
Drug Saf ; 47(5): 475-485, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38401041

RESUMO

INTRODUCTION AND OBJECTIVE: The European Medicines Agency (EMA) maintains a list of designated medical events (DMEs), events that are inherently serious and are prioritized for signal detection, irrespective of statistical criteria. We have analysed the results of our previously published scoping review to determine whether DME signals differ from those of other adverse events in terms of time to communication and characteristics of supporting reports of suspected adverse drug reactions. METHODS: For all signals, we obtained the launch year of medicinal products from textbooks or regulatory agencies, extracted the year of the first report in VigiBase and calculated the interval between the first report and communication (time to communication, TTC). We further retrieved the average completeness (via vigiGrade) of the reports in each case series in the years before the communication. We categorised as DME signals those concerning an event in the EMA's list. We described the two groups of signals using medians and interquartile ranges (IQR) and compared them using the Brunner-Munzel test, calculating 95% confidence intervals (95% CI) and P values. RESULTS: Of 4520 signals, 919 concerned DMEs and 3601 concerned non-DMEs. Signals of DMEs were supported by a median of 15 reports (IQR 6-38 reports) with a completeness score of 0.52 (IQR 0.43-0.62) and signals of non-DMEs by 20 reports (IQR 6-84 reports) with a completeness score of 0.46 (IQR 0.38-0.56). The probability that a random DME signal was supported by fewer reports than non-DME signals was 0.56 (95% CI 0.54-0.58, P < 0.001) and that of one having lower average completeness was 0.39 (95% CI 0.36-0.41, P < 0.001). The median TTCs of DME and non-DME signals did not differ (10 years), but the TTC was as low as 2 years when signals (irrespective of classification) were supported by reports whose average completeness was > 0.80. CONCLUSIONS: Signals of designated medical events were supported by fewer reports and higher completeness scores than signals of other adverse events. Although statistically significant, the differences in effect sizes between the two groups were small. This suggests that listing certain adverse events as DMEs is not having the expected effect of encouraging a focus on reports of the types of suspected adverse reactions that deserve special attention. Further enhancing the completeness of the reports of suspected adverse drug reactions supporting signals of designated medical events might shorten their time to communication and reduce the number of reports required to support them.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imidazóis , Compostos de Organossilício , Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Probabilidade , Comunicação
5.
Chemosphere ; 352: 141454, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38354863

RESUMO

Dimethylsilanediol (DMSD) is the degradation product of methylsiloxane polymers and oligomers such as volatile cyclic methylsiloxanes (cVMS). To better understand the environmental fate of this key degradation product, we conducted a three-part study on the movement of DMSD in soil. The objective of this third and final study was to determine the fate of DMSD in soil-plant systems under constant irrigation. Soil columns were constructed using two soils with the upper 20 cm layers spiked with 14C-labeled DMSD. Corn seedlings were transplanted into the soil columns and placed in a field plot underneath a transparent cover that prevented rainwater from reaching the soil columns while allowing soil water to be volatilized freely. The soil-plant columns were regularly irrigated with known amounts of DMSD-free plant growth solution to sustain the plant growth. At pre-determined time intervals (15-67 days), the plant and soil columns were sectioned and the distribution of 14Corganosilicon species in the soil profile and plant parts was determined using a combination of Liquid Scintillation Counting and High-Performance Liquid Chromatography-Flow Scintillation Analysis, while soil water loss was determined gravimetrically. It was found that the majority (>92 %) of DMSD initially spiked into the soil was removed from the soil-plant systems. Although DMSD was transported from the soil to the plant, it was subsequently volatilized from the plant via transpiration, with only a small fraction (∼5%) remaining at the conclusion of the experiments. In addition, little non-extractable DMSD was found in the top layer of soil in the soil-plant systems, suggesting that the air-drying of soil is a necessary pre-condition for the formation of such non-extractable silanol residue on topsoil.


Assuntos
Compostos de Organossilício , Poluentes do Solo , Poluentes Químicos da Água , Solo , Água , Poluentes Químicos da Água/análise , Poluentes do Solo/análise
6.
PeerJ ; 12: e16856, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313008

RESUMO

Background: Skin flap transplantation is one of the effective methods to treat the diabetes-related foot ulceration, but the intrinsic damage to vessels in diabetes mellitus (DM) leads to the necrosis of skin flaps. Therefore, the discovery of a non-invasive and effective approach for promoting the survival of flaps is of the utmost importance. Electrical stimulation (ES) promotes angiogenesis and increases the proliferation, migration, and elongation of endothelial cells, thus being a potential effective method to improve flap survival. Objective: The purpose of this study was to elucidate the mechanism used by ES to effectively restore the impaired function of endothelial cells caused by diabetes. Methods: A total of 79 adult male Sprague-Dawley rats were used in this study. Gene and protein expression was assessed by PCR and western blotting, respectively. Immunohistochemistry and hematoxylin-eosin staining were performed to evaluate the morphology and density of the microvessels in the flap. Results: The optimal duration for preconditioning the flap with ES was 7 days. The flap survival area percentage and microvessels density in the DMES group were markedly increased compared to the DM group. VEGF, MMP2, and MMP9 protein expression was significantly upregulated. ROS intensity was significantly decreased and GSH concentration was increased. The expression of IL-1ß, MCP­1, cleaved caspase-3, and Bax were downregulated in the DMES group, while TGF-ß expression was upregulated. Conclusions: ES improves the angiogenesis in diabetic ischemic skin flaps by attenuating oxidative stress-mediated inflammation and apoptosis, eventually increasing their viability.


Assuntos
Diabetes Mellitus , Imidazóis , Compostos de Organossilício , Retalho Perfurante , Ratos , Masculino , Animais , Ratos Sprague-Dawley , 60489 , Células Endoteliais , Neovascularização Fisiológica , Apoptose , Inflamação , Estresse Oxidativo , Estimulação Elétrica
7.
Chemosphere ; 352: 141478, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364924

RESUMO

Dimethylsilanediol (DMSD) is a primary degradation product of silicone materials in the environment. Due to its low air/water partition coefficient and low soil/water distribution coefficient, this compound is not expected to undergo sorption and volatilization in wet soil. In an accompanying paper, we confirm that under controlled indoor conditions in test tubes, there is little to no volatilization of DMSD from soil and soil constituents if soil is wet. However, a significant amount of DMSD was volatilized when the soil substrates became air dried. Given the importance of water on the partition and fate of DMSD, we now report a continuation of this study focusing on the relation between DMSD removal and water loss in re-constituted soil columns under outdoor conditions. Consistent with predictions based on its partition properties and reconciling this evidence with previously reported field and laboratory studies, DMSD distribution was found to be largely dependent on water partitioning. The results suggested that DMSD moved upward in soil profile as soil water was evaporated from topmost layers with little DMSD retention by the soil matrix. As soil dried, a fraction of DMSD was sorbed by the soil matrix in the topmost layer, while most of the spiked radio-labeled DMSD was removed from soil through volatilization.


Assuntos
Compostos de Organossilício , Poluentes do Solo , Água/química , Solo , Silicones , Poluentes do Solo/análise
8.
Mikrochim Acta ; 191(3): 153, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393379

RESUMO

This study introduces aptamer-functionalized polyhedral oligomeric silsesquioxane (POSS) nanoparticles for adenosine triphosphate (ATP) detection where the POSS nanoparticles were synthesized in a one-step, continuous flow microfluidic reactor utilizing thermal polymerization. A microemulsion containing POSS monomers was generated in the microfluidic reactor which was designed to prevent clogging by using a continuous oil flow around the emulsion during thermal polymerization. Surfaces of POSS nanoparticles were biomimetically modified by polydopamine. The aptamer sequence for ATP was successfully attached to POSS nanoparticles. The aptamer-modified POSS nanoparticles were tested for affinity-based biosensor applications using ATP as a model molecule. The nanoparticles were able to capture ATP molecules successfully with an affinity constant of 46.5 [Formula: see text]M. Based on this result, it was shown, for the first time, that microfluidic synthesis of POSS nanoparticles can be utilized in designing aptamer-functionalized nanosystems for biosensor applications. The integration of POSS in biosensing technologies not only exemplifies the versatility and efficacy of these nanoparticles but also marks a significant contribution to the field of biorecognition and sample preparation.


Assuntos
Técnicas Biossensoriais , Nanopartículas , Compostos de Organossilício , Trifosfato de Adenosina , Microfluídica , Oligonucleotídeos
9.
J Hazard Mater ; 466: 133470, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38246053

RESUMO

Quaternary ammonium compounds (QACs) are commonly used as disinfectants for industrial, medical, and residential applications. However, adverse health outcomes have been reported. Therefore, biocompatible disinfectants must be developed to reduce these adverse effects. In this context, QACs with various alkyl chain lengths (C12-C18) were synthesized by reacting QACs with the counterion silane. The antimicrobial activities of the novel compounds against four strains of microorganisms were assessed. Several in vivo assays were conducted on Drosophila melanogaster to determine the toxicological outcomes of Si-QACs, followed by computational analyses (molecular docking, simulation, and prediction of skin sensitization). The in vivo results were combined using a cheminformatics approach to understand the descriptors responsible for the safety of Si-QAC. Si-QAC-2 was active against all tested bacteria, with minimal inhibitory concentrations ranging from 13.65 to 436.74 ppm. Drosophila exposed to Si-QAC-2 have moderate-to-low toxicological outcomes. The molecular weight, hydrophobicity/lipophilicity, and electron diffraction properties were identified as crucial descriptors for ensuring the safety of the Si-QACs. Furthermore, Si-QAC-2 exhibited good stability and notable antiviral potential with no signs of skin sensitization. Overall, Si-QAC-2 (C14) has the potential to be a novel disinfectant.


Assuntos
Desinfetantes , Compostos de Organossilício , Compostos de Amônio Quaternário , Animais , Compostos de Amônio Quaternário/toxicidade , Silanos , Desinfetantes/toxicidade , Drosophila melanogaster , Simulação de Acoplamento Molecular
10.
Int J Pharm ; 652: 123852, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38280501

RESUMO

This study comprises the comprehensive toxicological assessment of thiolated organosilica nanoparticles (NPs) synthesised from 3-mercaptopropyltrimethoxysilane (MPTS). We investigated the influence of three different types of nanoparticles synthesised from 3-mercaptopropyltrimethoxysilane: the starting thiolated silica (Si-NP-SH) and their derivatives prepared by surface PEGylation with PEG 750 (Si-NP-PEG750) and 5000 Da (Si-NP-PEG5000) on biological subjects from in vitro to in vivo experiments to explore the possible applications of those nanoparticles in biomedical research. As a result of this study, we generated a comprehensive understanding of the toxicological properties of these nanoparticles, including their cytotoxicity in different cell lines, hemolytic properties, in vitro localisation, mucosal irritation properties and biodistribution in BALB/c mice. Our findings indicate that all three types of nanoparticles can be considered safe and have promising prospects for use in biomedical applications. Nanoparticles did not affect the viability of HPF, MCF7, HEK293 and A549 cell lines at low concentrations (up to 100 µg/mL); moreover, they did not cause organ damage to BALB/c mice at concentrations of 10 mg/kg. The outcomes of this study enhance our understanding of the impact of organosilica nanoparticles on health and the environment, which is vital for developing silica nanoparticle-based drug delivery systems and provides opportunities to expand the applications of organosilica nanoparticles.


Assuntos
Nanopartículas , Compostos de Organossilício , Humanos , Camundongos , Animais , Distribuição Tecidual , Células HEK293 , Nanopartículas/toxicidade , Dióxido de Silício/toxicidade , Polietilenoglicóis/toxicidade
11.
Clin Pharmacol Ther ; 115(2): 221-230, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37739780

RESUMO

First pass metabolism by phase I and phase II enzymes in the intestines and liver is a major determinant of the oral bioavailability of many drugs. Several studies analyzed expressions of major drug-metabolizing enzymes (DMEs), such as CYP3A4 and UGT1A1 in the human gut and liver. However, there is still a lack of knowledge regarding other DMEs (i.e., "minor" DMEs), although several clinically relevant drugs are affected by those enzymes. Moreover, there is very limited intra-subject data on hepatic and intestinal expression levels of minor DMEs. To fill this gap of knowledge, we analyzed gene expression (quantitative real-time polymerase chain reaction) and protein abundance (targeted proteomics) of 24 clinically relevant DMEs, that is, carboxylesterases (CES), UDP-glucuronosyltransferases (UGT), and cytochrome P450 (CYP)-enzymes. We performed our analysis using jejunum and liver tissue specimens from the same 11 healthy organ donors (8 men and 3 women, aged 19-60 years). Protein amounts of all investigated DMEs, with the exception of CYP4A11, were detected in human liver samples. CES2, CYP2C18, CYP3A4, and UGT2B17 protein abundance was similar or even higher in the jejunum, and all other DMEs were found in higher amounts in the liver. Significant correlations between gene expression and protein levels were observed only for 2 of 15 jejunal, but 13 of 23 hepatic DMEs. Intestinal and hepatic protein amounts only significantly correlated for CYP3A4 and UGT1A3. Our results demonstrated a notable variability between the individuals, which was even higher in the intestines than in the liver. Our intrasubject analysis of DMEs in the jejunum and liver from healthy donors, may be useful for physiologically-based pharmacokinetic-based modeling and prediction in order to improve efficacy and safety of oral drug therapy.


Assuntos
Citocromo P-450 CYP3A , Imidazóis , Jejuno , Compostos de Organossilício , Masculino , Humanos , Feminino , Jejuno/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Fígado/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Expressão Gênica
12.
Mol Omics ; 20(2): 115-127, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-37975521

RESUMO

Several software packages are available for the analysis of proteomic LC-MS/MS data, including commercial (e.g. Mascot/Progenesis LC-MS) and open access software (e.g. MaxQuant). In this study, Progenesis and MaxQuant were used to analyse the same data set from human liver microsomes (n = 23). Comparison focussed on the total number of peptides and proteins identified by the two packages. For the peptides exclusively identified by each software package, distribution of peptide length, hydrophobicity, molecular weight, isoelectric point and score were compared. Using standard cut-off peptide scores, we found an average of only 65% overlap in detected peptides, with surprisingly little consistency in the characteristics of peptides exclusively detected by each package. Generally, MaxQuant detected more peptides than Progenesis, and the additional peptides were longer and had relatively lower scores. Progenesis-specific peptides tended to be more hydrophilic and basic relative to peptides detected only by MaxQuant. At the protein level, we focussed on drug-metabolising enzymes (DMEs) and transporters, by comparing the number of unique peptides detected by the two packages for these specific proteins of interest, and their abundance. The abundance of DMEs and SLC transporters showed good correlation between the two software tools, but ABC showed less consistency. In conclusion, in order to maximise the use of MS datasets, we recommend processing with more than one software package. Together, Progenesis and MaxQuant provided excellent coverage, with a core of common peptides identified in a very robust way.


Assuntos
Imidazóis , Compostos de Organossilício , Proteômica , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida , Peptídeos/química , Proteínas , Fígado/química
13.
Photochem Photobiol ; 100(1): 52-66, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37431229

RESUMO

To treat a life-threatening disease like cancer, photodynamic therapy (PDT) and sonodynamic therapy (SDT) methods were combined into sono-photodynamic therapy (SPDT) as an effective therapeutic solution. Each day, the usage of phthalocyanine sensitizers increases in the therapeutic applications as they have the ability to produce more reactive oxygen species. In this context, a new diaxially silicon phthalocyanine sensitizer, containing triazole and tert-butyl groups, was synthesized. After elucidating the structure of the complex with elemental analysis, FT-IR, UV-Vis, MALDI-TOF MS and 1 H NMR, its photophysical, photochemical and sono-photochemical properties were examined. When singlet oxygen generation capacity of the new synthesized silicon phthalocyanine complex was determined and compared among photochemical (PDT; Ð¤Δ = 0.59 in DMSO, 0.44 in THF, 0.47 in toluene) and sonophotochemical (SPDT; Ð¤Δ = 0.88 in dimethyl sulfoxide (DMSO), 0.60 in tetrahydrofuran (THF), 0.65 in toluene) methods, it can be said that the complex is a successful sono-photosensitizer that can be used as a good SPDT agent in vitro or in vivo future studies.


Assuntos
Indóis , Compostos de Organossilício , Fotoquimioterapia , Oxigênio Singlete , Oxigênio Singlete/química , Dimetil Sulfóxido , Espectroscopia de Infravermelho com Transformada de Fourier , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Tolueno
14.
Bioorg Med Chem Lett ; 97: 129192, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36813052

RESUMO

To investigate the renal protective effects of the polysaccharide LEP-1a and derivatives of selenium (SeLEP-1a) from Lachnum YM38, cisplatin (CP) was used to establish an acute kidney model. LEP-1a and SeLEP-1a could effectively reverse the decrease in renal index and improved renal oxidative stress. LEP-1a and SeLEP-1a significantly reduced the contents of the inflammatory cytokines. They could inhibit the release of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) and increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). At the same time, the PCR results indicated that SeLEP-1a could significantly inhibit the mRNA expression levels of toll-like receptor 4 (TLR4), nuclear factor-kB (NF-κB) p65 and inhibitor of kappa B-alpha (IκBα). Western blot analysis showed that LEP-1a and SeLEP-1a significantly downregulated the expression levels of Bcl-2-associated X protein (Bax) and cleaved caspase-3 and upregulated phosphatidylinositol 3-kinase (p-PI3K), protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl-2) protein expression levels in the kidney. LEP-1a and SeLEP-1a could improve CP-induced acute kidney injury by regulating the oxidative stress response, NF-κB-mediated inflammation and the PI3K/Akt-mediated apoptosis signalling pathway.


Assuntos
Injúria Renal Aguda , Polissacarídeos , Selênio , Animais , Camundongos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Cisplatino/farmacologia , Cisplatino/toxicidade , Rim/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Selênio/farmacologia , Compostos de Organossilício/metabolismo , Compostos de Organossilício/farmacologia
15.
Int J Nanomedicine ; 18: 6469-6486, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026537

RESUMO

Background: The respiratory system is intensely damaged by acute lung injury (ALI). The anti-inflammatory effects of tetramethylpyrazine (TMP) against ALI have been confirmed, but it exhibits a short half-life. miR-194-5p could directly target Rac1, but the internalization rate of miRNA cells was low. Purpose: To explore the potential of the soft mesoporous organic silica nanoplatform (NPs) as carriers for delivery of TMP and miR-194-5p through the tail vein. Methods: NPs@TMP and NPs@PEI@miR-194-5p were added to the HUVEC cell-lines, in vitro, to observe the cell uptake and cytotoxic effects. In vivo experiments were conducted by injecting fluorescently labeled NPs through the tail vein and tracking distribution. Therapeutic and toxic side-effects were analyzed systemically. Results: In vitro study exhibited that NPs have no toxic effect on HUVECs within the experimental parameters and have excellent cellular uptake. The IVIS Spectrum Imaging System shows that NPs accumulate mainly in the lungs. NPs@TMP treatment can improved oxidative stress and inflammation levels in ALI mice and inhibited the TLR4/NLRP3/caspase 1 pathway. NPs@PEI@miR-194-5p can inhibit the Rac1/ZO-1/occludin pathway and improved endothelial cell permeability in ALI mice. The co-treatment of NPs@TMP and NPs@PEI@miR-194-5p can significantly improved the survival rates of the mice, reduced pulmonary capillary permeability and improved pathological injury in ALI mice. Innovation: This study combined traditional Chinese medicine, bioinformatics, cellular molecular biology and nanobiomedicine to study the pathogenesis and treatment of ALI. The rate of cellular internalization was improved by changing the shape and hardness of nanoparticles. NPs@TMP and NPs@PEI@miR-194-5p combined application can significantly improve the survival condition and pathological injury of mice. Conclusion: NPs loaded with TMP and miR-194-5p showed a greater therapeutic effect in ALI mice.


Assuntos
Lesão Pulmonar Aguda , MicroRNAs , Compostos de Organossilício , Pirazinas , Animais , Humanos , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipopolissacarídeos , Pulmão/patologia , MicroRNAs/farmacologia , Compostos de Organossilício/farmacologia , Pirazinas/farmacologia
16.
Anal Chim Acta ; 1280: 341854, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37858549

RESUMO

BACKGROUND: Mg2+ has long been recognized as one of the most vital cations due to its diverse physiological and pathological roles, making it indispensable in both biomedical and biological research. Organic fluorescent sensors are commonly employed for Mg2+ detection, but they often lack high selectivity and exhibit poor hydrophilicity, limiting their biomedical applications. RESULTS: Herein, we introduced a novel organic-inorganic hybrid fluorescence sensor, PFHBS, constructed on the POSS nanoplatforms. The efficient connection between PEGylated POSS and the small molecule sensor FHBS through Click chemistry enhances the selectivity and reduces interference, making this chemical sensor ideal for the accurate detection of Mg2+. Furthermore, the incorporation of POSS amplifies the ligand field effect of FHBS, making it more conducive to Mg2+ capture. The modification of PEG chains enhances the sensor's amphiphilicity, facilitating efficient cell penetration and effective Mg2+ detection at the biological level. SIGNIFICANCE: Finally, relying on spontaneous permeation, coupled with its strong ligand field effect and excellent cell permeability, the chemosensor demonstrates the capability to intelligently remove excess Mg2+ from the body. It has been successfully applied to mitigate renal overload resulting from acute Mg2+ poisoning.


Assuntos
Compostos de Organossilício , Compostos de Organossilício/química , Magnésio , Ligantes , Corantes , Íons
17.
Anal Chim Acta ; 1279: 341785, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37827681

RESUMO

Extracellular vesicles (EVs) are important participants in numerous pathophysiological processes, and could be used as valuable biomarkers to detect and monitor various diseases. However, facile EV isolation methods are the essential and preliminary issue for their downstream analysis and function investigation. In this work, a polyhedral oligomeric silsesquioxanes (POSS) based hybrid monolith combined metal affinity chromatography (MAC) and distearoyl phospholipid ethanolamine (DSPE) function was developed via photo-initiated thiol-ene polymerization. This synthesis process was facile, simple and convenient, and the obtained hybrid monolith could be applied to efficiently isolate EVs from bio-samples by taking advantages of the specific bond of Ti4+ and phosphate groups on the phospholipid membrane of EVs and the synergistic effect of DSPE insertion. Meanwhile, the eluted EVs could maintain their structural integrity and biological activity, suggesting they could be used for downstream application. Furthermore, 75 up-regulated proteins and 56 down-regulated proteins were identified by comparing the urinary EVs of colorectal cancer (CRC) patients and healthy donors, and these proteins might be used as potential biomarkers for early screening of CRC. These results demonstrated that this hybrid monolith could be used as a simple and convenient tool for isolating EVs from bio-samples and for wider applications in biomarker discovery.


Assuntos
Vesículas Extracelulares , Compostos de Organossilício , Humanos , Compostos de Organossilício/química , Polimerização , Interações Hidrofóbicas e Hidrofílicas , Biomarcadores , Fosfolipídeos
18.
Carbohydr Polym ; 316: 121060, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37321743

RESUMO

Multifunctional biomass-based aerogels with mechanically robust and high fire safety are urgently needed for the development of environmentally-friendly intelligent fire fighting but challenging. Herein, a novel polymethylsilsesquioxane (PMSQ)/cellulose/MXene composite aerogel (PCM) with superior comprehensive performance was fabricated by ice-induced assembly and in-situ mineralization. It exhibited light weight (16.2 mg·cm-3), excellent mechanical resilience, and rapidly recovered after being subjected to the pressure of 9000 times of its own weight. Moreover, PCM demonstrated outstanding thermal insulation, hydrophobicity and sensitive piezoresistive sensing. In addition, benefiting from the synergism of PMSQ and MXene, PCM displayed good flame retardancy and improved thermostability. The limiting oxygen index of PCM was higher than 45.0 %, and it quickly self-extinguished after being removed away from fire. More importantly, the rapid electrical resistance reduction of MXene at high temperature endowed PCM with sensitive fire-warning capability (trigger time was less than 1.8 s), which provided valuable time for people to evacuate and relief. This work provides new insights for the preparation and application of the next-generation high performance biomass-based aerogels.


Assuntos
Celulose , Compostos de Organossilício , Humanos , Biomassa
19.
Nanoscale ; 15(25): 10484-10497, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37326150

RESUMO

Organosilica nanoparticles refer to silica nanoparticles containing carbon along with organic or functional groups and can be divided into mesoporous organosilica nanoparticles and nonporous organosilica nanoparticles. During the past few decades, considerable efforts have been devoted to the development of organosilica nanoparticles directly from organosilanes. However, most of the reports have focused on mesoporous organosilica nanoparticles, while relatively few are concerned with nonporous organosilica nanoparticles. The synthesis of nonporous organosilica nanoparticles typically involves (i) self-condensation of an organosilane as the single source, (ii) co-condensation of two or more types of organosilanes, (iii) co-condensation of tetraalkoxysilane and an organosilane, and (iv) spontaneous emulsification and the subsequent radical polymerization of 3-(trimethoxysilyl)propyl methacrylate (TPM). This article aims to provide a review on the synthetic strategies of this important type of colloidal particle, followed by a brief discussion on their applications and future perspectives.


Assuntos
Nanopartículas , Compostos de Organossilício , Dióxido de Silício
20.
Int J Mol Sci ; 24(12)2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37373114

RESUMO

The biologically active compound 3-aminopropylsilatrane (a compound with a pentacoordinated silicon atom) underwent an aza-Michael reaction with various acrylates and other Michael acceptors. Depending on the molar ratio, the reaction yielded Michael mono- or diadducts (11 examples) containing functional groups (silatranyl, carbonyl, nitrile, amino, etc.). These compounds were characterized via IR and NMR spectroscopy, mass spectrometry, X-ray diffraction, and elemental analysis. Calculations (using in silico, PASS, and SwissADMET online software) revealed that the functionalized (hybrid) silatranes were bioavailable, druglike compounds that exhibited pronounced antineoplastic and macrophage-colony-stimulating activity. The in vitro effect of silatranes on the growth of pathogenic bacteria (Listeria, Staphylococcus, and Yersinia) was studied. It was found that the synthesized compounds exerted inhibitory and stimulating effects in high and low concentrations, respectively.


Assuntos
Antineoplásicos , Compostos de Organossilício , Antineoplásicos/farmacologia , Antineoplásicos/química , Difração de Raios X , Espectrometria de Massas , Estrutura Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...