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1.
Nanomedicine ; 59: 102753, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734039

RESUMO

In this study, we have considered four types of nanoparticles (NPs): polylactic acid (PLA), gold (Au), calcium carbonate (CaCO3), and silica (SiO2) with similar sizes (TEM: 50-110 nm and DLS: 110-140 nm) to examine their passive accumulation in three different tumors: colon (CT26), melanoma (B16-F10), and breast (4T1) cancers. Our results demonstrate that each tumor model showed a different accumulation of NPs, in the following order: CT26 > B16-F10 > 4T1. The Au and PLA NPs were evidently characterized by a higher delivery efficiency in case of CT26 tumors compared to CaCO3 and SiO2 NPs. The Au NPs demonstrated the highest accumulation in B16-F10 cells compared to other NPs. These results were verified using SPECT, ex vivo fluorescence bioimaging, direct radiometry and histological analysis. Thus, this work contributes to new knowledge in passive tumor targeting of NPs and can be used for the development of new strategies for delivery of bioactive compounds.

2.
Polymers (Basel) ; 16(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38732653

RESUMO

Cellulose nitrates (CNs)-blended composites based on celluloses of bacterial origin (bacterial cellulose (BC)) and plant origin (oat-hull cellulose (OHC)) were synthesized in this study for the first time. Novel CNs-blended composites made of bacterial and plant-based celluloses with different BC-to-OHC mass ratios of 70/30, 50/50, and 30/70 were developed and fully characterized, and two methods were employed to nitrate the initial BC and OHC, and the three cellulose blends: the first method involved the use of sulfuric-nitric mixed acids (MAs), while the second method utilized concentrated nitric acid in the presence of methylene chloride (NA + MC). The CNs obtained using these two nitration methods were found to differ between each other, most notably, in viscosity: the samples nitrated with NA + MC had an extremely high viscosity of 927 mPa·s through to the formation of an immobile transparent acetonogel. Irrespective of the nitration method, the CN from BC (CN BC) was found to exhibit a higher nitrogen content than the CN from OHC (CN OHC), 12.20-12.32% vs. 11.58-11.60%, respectively. For the starting BC itself, all the cellulose blends of the starting celluloses and their CNs were detected using the SEM technique to have a reticulate fiber nanostructure. The cellulose samples and their CNs were detected using the IR spectroscopy to have basic functional groups. TGA/DTA analyses of the starting cellulose samples and the CNs therefrom demonstrated that the synthesized CN samples were of high purity and had high specific heats of decomposition at 6.14-7.13 kJ/g, corroborating their energy density. The CN BC is an excellent component with in-demand energetic performance; in particular, it has a higher nitrogen content while having a stable nanostructure. The CN BC was discovered to have a positive impact on the stability, structure, and energetic characteristics of the composites. The presence of CN OHC can make CNs-blended composites cheaper. These new CNs-blended composites made of bacterial and plant celluloses are much-needed in advanced, high-performance energetic materials.

3.
Biomedicines ; 12(5)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38790984

RESUMO

Forkhead box protein 3 (FoxP3) is a key transcription factor responsible for the development, maturation, and function of regulatory T cells (Tregs). The FoxP3 pre-mRNA is subject to alternative splicing, resulting in the translation of multiple splice variants. We have shown that Tregs from patients with amyotrophic lateral sclerosis (ALS) have reduced expression of full-length (FL) FoxP3, while other truncated splice variants are expressed predominantly. A correlation was observed between the reduced number of Tregs in the peripheral blood of ALS patients, reduced total FoxP3 mRNA, and reduced mRNA of its FL splice variant. Induction of FL FoxP3 was achieved using splice-switching oligonucleotides capable of base pairing with FoxP3 pre-mRNA and selectively modulating the inclusion of exons 2 and 7 in the mature mRNA. Selective expression of FL FoxP3 resulted in the induction of CD127low, CD152, and Helios-positive cells, while the cell markers CD4 and CD25 were not altered. Such Tregs had an increased proliferative activity and a higher frequency of cell divisions per day. The increased suppressive activity of Tregs with the induced FL FoxP3 splice variant was associated with the increased synthesis of the pro-apoptotic granzymes A and B, and perforin, IL-10, and IL-35, which are responsible for contact-independent suppression, and with the increased ability to suppress telomerase in target cells. The upregulation of Treg suppressive and proliferative activity using splice-switching oligonucleotides to induce the predominant expression of the FoxP3 FL variant is a promising approach for regenerative cell therapy in Treg-associated diseases.

4.
Med ; 5(5): 377-379, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38733969

RESUMO

The study by Hirschfield et al.1 demonstrated safety profile and clinically significant effectiveness of the peroxisome proliferator-activated receptor delta (PPARδ) agonist seladelpar in patients with primary biliary cholangitis, highlighting its plausible use as a second-line treatment to reduce disease activity and pruritus.


Assuntos
Cirrose Hepática Biliar , Prurido , Humanos , Prurido/tratamento farmacológico , Cirrose Hepática Biliar/tratamento farmacológico , PPAR delta/agonistas , PPAR delta/metabolismo
5.
Front Nutr ; 11: 1393014, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699545

RESUMO

Background: Alcohol misuse, binge drinking pattern, and gender-specific effects in the middle-aged population has been clearly underestimated. In the present study, we focused on understanding gender-specific effects of alcohol exposure on the gut-liver axis and the role of gut microbiota in modulating gender-specific responses to alcohol consumption. Methods: Fifty-two-week-old female and male C57BL/6 mice were fasted for 12 h, and then administered a single oral dose of ethanol (EtOH) (6 g/kg). Controls were given a single dose of PBS. Animals were sacrificed 8 h later. Alternatively, fecal microbiota transplantation (FMT) was performed in 52-week-old male mice from female donors of the same age. Permeability of the large intestine (colon), gut microbiota, liver injury, and inflammation was thoroughly evaluated in all groups. Results: Middle-aged male mice exposed to EtOH showed a significant increase in gut permeability in the large intestine, evaluated by FITC-dextran assay and ZO-1, OCCLUDIN and MUCIN-2 immuno-staining, compared to PBS-treated animals, whilst female mice of the same age also increased their gut permeability, but displayed a partially maintained intestinal barrier integrity. Moreover, there was a significant up-regulation of TLRs and markers of hepatocellular injury, cell death (AST, TUNEL-positive cells) and lipid accumulation (ORO) in male mice after EtOH exposure. Interestingly, FMT from female donors to male mice reduced gut leakiness, modified gut microbiota composition, ameliorated liver injury and inflammation, TLR activation and the senescence phenotype of middle-aged mice. Conclusion: Our findings highlighted the relevance of gender in middle-aged individuals who are exposed to alcohol in the gut-liver axis. Moreover, our study revealed that gender-specific microbiota transplantation might be a plausible therapy in the management of alcohol-related disorders during aging.

6.
Transl Behav Med ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718172

RESUMO

Collaborative data science requires standardized, harmonized, interoperable, and ethically sourced data. Developing an agreed-upon set of elements requires capturing different perspectives on the importance and feasibility of the data elements through a consensus development approach. This study reports on the systematic scoping review of literature that examined the inclusion of diverse stakeholder groups and sources of social drivers of health variables in consensus-based common data element (CDE) sets. This systematic scoping review included sources from PubMed, Embase, CINAHL, WoS MEDLINE, and PsycINFO databases. Extracted data included the stakeholder groups engaged in the Delphi process, sources of CDE sets, and inclusion of social drivers data across 11 individual and 6 social domains. Of the 384 studies matching the search string, 22 were included in the final review. All studies involved experts with healthcare expertise directly relevant to the developed CDE set, and only six (27%) studies engaged health consumers. Literature reviews and expert input were the most frequent sources of CDE sets. Seven studies (32%) did not report the inclusion of any demographic variables in the CDE sets, and each demographic SDoH domain was included in at least one study with age and sex assigned at birth included in all studies, and social driver domains included only in four studies (18%). The Delphi technique engages diverse expert groups around the development of SDoH data elements. Future studies can benefit by involving health consumers as experts.


Collecting and capturing social factors that affect individuals' health is imperative. Social drivers of health data allow researchers to understand health disparities to make healthcare available, accessible, and affordable. However, collecting common health data elements has challenged researchers due to limited resources to facilitate change. Incorporating various stakeholders, such as individuals and patient advocacy groups, can effectively contribute to the research process as community advisors. This article reviews the studies that used the Delphi method and brings together experts to agree on guidelines for collecting common data elements. The article's findings reveal that experts are healthcare professionals and researchers, leaving out the crucial input from patients and caregivers. This article emphasized that developing a standard set of data elements can improve the standardization of social drivers of health. Common data elements provide the opportunity to improve patients' and social circumstances and their efforts toward health outcomes.

7.
PNAS Nexus ; 3(4): pgae131, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38595801

RESUMO

Organisms from microbes to humans engage in a variety of social behaviors, which affect fitness in complex, often nonlinear ways. The question of how these behaviors evolve has consequences ranging from antibiotic resistance to human origins. However, evolution with nonlinear social interactions is challenging to model mathematically, especially in combination with spatial, group, and/or kin assortment. We derive a mathematical condition for natural selection with synergistic interactions among any number of individuals. This result applies to populations with arbitrary (but fixed) spatial or network structure, group subdivision, and/or mating patterns. In this condition, nonlinear fitness effects are ascribed to collectives, and weighted by a new measure of collective relatedness. For weak selection, this condition can be systematically evaluated by computing branch lengths of ancestral trees. We apply this condition to pairwise games between diploid relatives, and to dilemmas of collective help or harm among siblings and on spatial networks. Our work provides a rigorous basis for extending the notion of "actor", in the study of social evolution, from individuals to collectives.

8.
PLoS One ; 19(4): e0300974, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38630773

RESUMO

SCORE2 (Systematic COronary Risk Evaluation 2) is a risk assessment scale for cardiovascular events, presented in 2021 by the European Society of Cardiology. Both for training and validation of the SCORE2 model, representative samples from the Russian population were not used. Therefore, we aimed to validate SCORE2 on a such sample. For this purpose, we used a sample from the ESSE-RF epidemiological study consisting of 7251 participants aged 40-69 years without history of CVDs. We performed the validation by comparing SCORE2 risk estimates for ESSE-RF participants with the observed incidence of cardiovascular events in the study, adjusted for event information losses. The validation demonstrated that SCORE2 risk estimates were accurate for Russian men and inaccurate for Russian women. Together with the quantitative assessment of risk, SCORE2 offers its interpretation in terms of 10-year CVD risk group: low-moderate, high, and very high. For Russian men we considered the original interpretation of the SCORE2 estimates to be questionable because almost none of the men would be categorized as having "low-to-moderate" 10-year CVD risk. This problem would be typical for all countries of the very high CVD risk region. Therefore, we proposed a new interpretation of the SCORE2 risk estimates for men from the very high risk region. According to the proposed interpretation, the fraction of men in ESSE-RF in "low-to-moderate" 10-year CVD risk increased from 2% to 18% and the fraction of men in "very high" CVD risk decreased from 63% to 20% as compared to the original interpretation. The proposed interpretation would allow a more personalized approach to CVD treatment and optimize the burden on primary healthcare in the very high risk region countries.


Assuntos
Cardiologia , Doenças Cardiovasculares , Masculino , Humanos , Feminino , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Medição de Risco , Federação Russa/epidemiologia
9.
J Clin Transl Sci ; 8(1): e58, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655458

RESUMO

Social determinants of health affect clinical and translational research processes and outcomes but remain underreported in empirical studies. This scoping review examined the rate and types of social determinants of health (SDoH) variables included in the JCTS translational research studies published between 2017 and 2023 and included 129 studies. Most papers (91.7%) reported at least one SDoH variable with age, race and ethnicity, and sex included most often. Future studies to inform the role of SDoH data in translational research and science are recommended, and a draft SDoH data checklist is provided.

10.
Biology (Basel) ; 13(4)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38666835

RESUMO

This methodological study describes the adaptation of a new method in digital wood anatomy, pixel-contrast densitometry, for angiosperm species. The new method was tested on eight species of shrubs and small trees in Southern Siberia, whose wood structure varies from ring-porous to diffuse-porous, with different spatial organizations of vessels. A two-step transformation of wood cross-section photographs by smoothing and Otsu's classification algorithm was proposed to separate images into cell wall areas and empty spaces within (lumen) and between cells. Good synchronicity between measurements within the ring allowed us to create profiles of wood porosity (proportion of empty spaces) describing the growth ring structure and capturing inter-annual differences between rings. For longer-lived species, 14-32-year series from at least ten specimens were measured. Their analysis revealed that maximum (for all wood types), mean, and minimum porosity (for diffuse-porous wood) in the ring have common external signals, mostly independent of ring width, i.e., they can be used as ecological indicators. Further research directions include a comparison of this method with other approaches in densitometry, clarification of sample processing, and the extraction of ecologically meaningful data from wood structures.

11.
Int J Mol Sci ; 25(8)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38673928

RESUMO

There are two paralogs of glutamate dehydrogenase (GDH) in humans encoded by the GLUD1 and GLUD2 genes as a result of a recent retroposition during the evolution of primates. The two human GDHs possess significantly different regulation by allosteric ligands, which is not fully characterized at the structural level. Recent advances in identification of the GDH ligand binding sites provide a deeper perspective on the significance of the accumulated substitutions within the two GDH paralogs. In this review, we describe the evolution of GLUD1 and GLUD2 after the duplication event in primates using the accumulated sequencing and structural data. A new gibbon GLUD2 sequence questions the indispensability of ancestral R496S and G509A mutations for GLUD2 irresponsiveness to GTP, providing an alternative with potentially similar regulatory features. The data of both GLUD1 and GLUD2 evolution not only confirm substitutions enhancing GLUD2 mitochondrial targeting, but also reveal a conserved mutation in ape GLUD1 mitochondrial targeting sequence that likely reduces its transport to mitochondria. Moreover, the information of GDH interactors, posttranslational modification and subcellular localization are provided for better understanding of the GDH mutations. Medically significant point mutations causing deregulation of GDH are considered from the structural and regulatory point of view.


Assuntos
Evolução Molecular , Glutamato Desidrogenase , Processamento de Proteína Pós-Traducional , Animais , Humanos , Glutamato Desidrogenase/metabolismo , Glutamato Desidrogenase/genética , Glutamato Desidrogenase/química , Ligantes , Mutação , Primatas/genética
12.
Int J Mol Sci ; 25(8)2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38673903

RESUMO

Cardiotonic steroids (CTSs), such as digoxin, are used for heart failure treatment. However, digoxin permeates the brain-blood barrier (BBB), affecting central nervous system (CNS) functions. Finding a CTS that does not pass through the BBB would increase CTSs' applicability in the clinic and decrease the risk of side effects on the CNS. This study aimed to investigate the tissue distribution of the CTS ouabain following intraperitoneal injection and whether ouabain passes through the BBB. After intraperitoneal injection (1.25 mg/kg), ouabain concentrations were measured at 5 min, 15 min, 30 min, 1 h, 3 h, 6 h, and 24 h using HPLC-MS in brain, heart, liver, and kidney tissues and blood plasma in C57/black mice. Ouabain was undetectable in the brain tissue. Plasma: Cmax = 882.88 ± 21.82 ng/g; Tmax = 0.08 ± 0.01 h; T1/2 = 0.15 ± 0.02 h; MRT = 0.26 ± 0.01. Cardiac tissue: Cmax = 145.24 ± 44.03 ng/g (undetectable at 60 min); Tmax = 0.08 ± 0.02 h; T1/2 = 0.23 ± 0.09 h; MRT = 0.38 ± 0.14 h. Kidney tissue: Cmax = 1072.3 ± 260.8 ng/g; Tmax = 0.35 ± 0.19 h; T1/2 = 1.32 ± 0.76 h; MRT = 1.41 ± 0.71 h. Liver tissue: Cmax = 2558.0 ± 382.4 ng/g; Tmax = 0.35 ± 0.13 h; T1/2 = 1.24 ± 0.7 h; MRT = 0.98 ± 0.33 h. Unlike digoxin, ouabain does not cross the BBB and is eliminated quicker from all the analyzed tissues, giving it a potential advantage over digoxin in systemic administration. However, the inability of ouabain to pass though the BBB necessitates intracerebral administration when used to investigate its effects on the CNS.


Assuntos
Camundongos Endogâmicos C57BL , Ouabaína , Animais , Distribuição Tecidual , Injeções Intraperitoneais , Camundongos , Masculino , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Espectrometria de Massas/métodos , Rim/metabolismo , Rim/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Miocárdio/metabolismo , Cardiotônicos/farmacocinética , Cardiotônicos/farmacologia , Cardiotônicos/administração & dosagem
13.
Gut Microbes ; 16(1): 2331460, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512763

RESUMO

Obesity, insulin resistance (IR), and the gut microbiome intricately interplay in Metabolic-associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease (NAFLD), a growing health concern. The complex progression of MASLD extends beyond the liver, driven by "gut-liver axis," where diet, genetics, and gut-liver interactions influence disease development. The pathophysiology of MASLD involves excessive liver fat accumulation, hepatocyte dysfunction, inflammation, and fibrosis, with subsequent risk of hepatocellular carcinoma (HCC). The gut, a tripartite barrier, with mechanical, immune, and microbial components, engages in a constant communication with the liver. Recent evidence links dysbiosis and disrupted barriers to systemic inflammation and disease progression. Toll-like receptors (TLRs) mediate immunological crosstalk between the gut and liver, recognizing microbial structures and triggering immune responses. The "multiple hit model" of MASLD development involves factors like fat accumulation, insulin resistance, gut dysbiosis, and genetics/environmental elements disrupting the gut-liver axis, leading to impaired intestinal barrier function and increased gut permeability. Clinical management strategies encompass dietary interventions, physical exercise, pharmacotherapy targeting bile acid (BA) metabolism, and microbiome modulation approaches through prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). This review underscores the complex interactions between diet, metabolism, microbiome, and their impact on MASLD pathophysiology and therapeutic prospects.


Assuntos
Carcinoma Hepatocelular , Microbioma Gastrointestinal , Resistência à Insulina , Neoplasias Hepáticas , Humanos , Disbiose , Inflamação , Homeostase
14.
Methods Mol Biol ; 2791: 35-43, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38532090

RESUMO

The study of the localization of secondary metabolites in both plants and the cell cultures on the intravital sections is hampered by the difficulty of obtaining thin, correctly oriented sections. Techniques for fixing tissues in resins allow these difficulties to be overcome. Properly selected tissue fixation techniques allow using different dyes to identify the compound of interest. In addition, some components of tissue fixation can act as fixatives and as a dye for identifying secondary metabolites. For example, osmium tetroxide, which fixes lipids in tissues, stains phenolic compounds black. This paper describes methods for the detection of phenolic compounds in morphogenic callus culture of buckwheat using osmium tetroxide, Toluidine Blue O dye, and ferric chloride as dyes in epoxy resin-embedded cell culture with double fixation of the material and when material fixed in Karnovsky's fixative.


Assuntos
Corantes , Fagopyrum , Compostos Férricos , Tetróxido de Ósmio , Cloretos , Cloreto de Tolônio , Fixadores , Fixação de Tecidos , Técnicas de Cultura de Células , Ferro , Osmio
15.
ACS Appl Bio Mater ; 7(4): 2472-2487, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38480461

RESUMO

Local recurrence after surgical and therapeutic treatment remains a significant clinical problem in oncology. Recurrence may be due to imperfections in existing therapies, particularly chemotherapy. To improve antitumor activity and prevent local cancer recurrence while keeping toxicity at acceptable levels, we have developed and demonstrated a biodegradable local chemotherapy platform that provides controlled and prolonged drug release. The platform consists of a polycaprolactone (PCL) substrate, which provides the structural integrity of the platform and the predominant unidirectional drug release, and a thin multilayer coating (∼200 nm) containing doxorubicin (DOX). The coating is an electrostatic complex obtained by the layer-by-layer (LbL) assembly and consists of natural polyelectrolytes [poly-γ-glutamic acid (γ-PGA) and chitosan (CS) or poly-l-lysine (PLL)]. To improve the release stability, an ionic conjugate of DOX and γ-PGA was prepared and incorporated into the multilayer coating. By varying the structure of the coating by adding empty (without DOX) bilayers, we were able to control the kinetics of drug release. The resulting platforms contained equal numbers of empty bilayers and DOX-loaded bilayers (15 + 15 or 30 + 30 bilayers) with a maximum loading of 566 ng/cm2. The platforms demonstrated prolonged and fairly uniform drug release for more than 5 months while retaining antitumor activity in vitro on ovarian cancer cells (SKOV-3). The empty platforms (without DOX) showed good cytocompatibility and no cytotoxicity to human fibroblasts and SKOV-3 cells. This study presents the development of a local chemotherapy platform consisting of a PCL-based substrate which provides structural stability and a biodegradable polyelectrolyte layered coating which combines layers containing a polyanion ionic complex with DOX with empty bilayers to ensure prolonged and controlled drug release. Our results may provide a basis for improving the efficacy of chemotherapy using drug delivery systems.


Assuntos
Nanopartículas , Recidiva Local de Neoplasia , Humanos , Preparações de Ação Retardada , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química
16.
Free Radic Biol Med ; 216: 24-32, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460742

RESUMO

Reactive oxygen species (ROS) produced by NADPH oxidases (NOX, a key source of ROS in vascular cells) are involved in the regulation of vascular tone, but this has been explored mainly for adult organisms. Importantly, the mechanisms of vascular tone regulation differ significantly in early postnatal ontogenesis and adulthood, while the vasomotor role of ROS in immature systemic arteries is poorly understood. We tested the hypothesis that the functional contribution of NADPH oxidase-derived ROS to the regulation of peripheral arterial tone is higher in the early postnatal period than in adulthood. We studied saphenous arteries from 10- to 15-day-old ("young") and 3- to 4-month-old ("adult") male rats using lucigenin-enhanced chemiluminescence, quantitative PCR, Western blotting, and isometric myography. We demonstrated that both basal and NADPH-stimulated superoxide anion radical (O2•-) production was significantly higher in the arteries from young in comparison to adult rats. Importantly, pan-inhibitor of NADPH oxidase VAS2870 (10 µM) reduced NADPH-induced O2•- production in arteries of young rats. Saphenous arteries of both young and adult rats demonstrated high levels of Nox2 and Nox4 mRNAs, while Nox1 and Nox3 mRNAs were not detected. The protein contents of NOX2 and NOX4 were significantly higher in arterial tissue of young compared to adult animals. Moreover, VAS2870 (10 µM) had no effect on methoxamine-induced contractile responses of adult arteries but decreased them significantly in young arteries; such effect of VAS2870 persisted after removal of the endothelium. Finally, NOX2 inhibitor GSK2795039 (10 µM), but not NOX1/4 inhibitor GKT137831 (10 µM) weakened methoxamine-induced contractile responses of arteries from young rats. Thus, ROS produced by NOX2 have a pronounced contractile influence in saphenous artery smooth muscle cells of young, but not adult rats, which is associated with the increased vascular content of NOX2 protein at this age.


Assuntos
Artérias , NADPH Oxidases , Ratos , Masculino , Animais , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , NADP , Metoxamina , Artérias/fisiologia , NADPH Oxidase 1/genética , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , Superóxidos/metabolismo
17.
ACS Biomater Sci Eng ; 10(4): 2324-2336, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38520335

RESUMO

Many methods for cancer treatment have been developed. Among them photothermal therapy (PTT) has drawn the most significant attention due to its noninvasiveness, remote control activation, and low side effects. However, a limited depth of light penetration of PTT is the main drawback. To improve the therapeutic efficiency, the development of combined PTT with other therapeutic agents is highly desirable. In this work, we have designed multifunctional composite carriers based on polylactic acid (PLA) particles decorated with gold nanorods (Au NRs) as nanoheaters and selenium nanoparticles (Se NPs) for reactive oxygen species (ROS) production in order to perform a combined PTT against B16-F10 melanoma. To do this, we have optimized the synthesis of PLA particles modified with Se NPs and Au NRs (PLA-Se:Au), studied the cellular interactions of PLA particles with B16-F10 cells, and analyzed in vivo biodistribution and tumor inhibition efficiency. The results of in vitro and in vivo experiments demonstrated the synergistic effect from ROS induced by Se NPs and the heating from Au NRs. In melanoma tumor-bearing mice, intratumoral injection of PLA-Se:Au followed by laser irradiation leads to almost complete elimination of tumor tissues. Thus, the optimal photothermal properties and ROS-generating capacity allow us to recommend PLA-Se:Au as a promising candidate for the development of the combined PTT against melanoma.


Assuntos
Hipertermia Induzida , Melanoma , Nanopartículas Metálicas , Animais , Camundongos , Melanoma/terapia , Espécies Reativas de Oxigênio , Distribuição Tecidual , Nanopartículas Metálicas/uso terapêutico , Poliésteres
18.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474299

RESUMO

NanoFAST is the smallest fluorogen-activating protein, consisting of only 98 amino acids, used as a genetically encoded fluorescent tag. Previously, only a single fluorogen with an orange color was revealed for this protein. In the present paper, using rational mutagenesis and in vitro screening of fluorogens libraries, we expanded the color palette of this tag. We discovered that E46Q is one of the key substitutions enabling the range of possible fluorogens to be expanded. The introduction of this and several other substitutions has made it possible to use not only orange but also red and green fluorogens with the modified protein.


Assuntos
Corantes Fluorescentes , Proteínas , Corantes Fluorescentes/química
19.
Int J Mol Sci ; 25(6)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38542403

RESUMO

Polyphenolic compounds are of great interest in today's science. Naturally, they occur in plants and other sources in many different forms. Their wide range of biological activity has attracted the attention of the scientific community. One of the sources of phenolic compounds is stinging nettle (Urtica dioica L.), a common plant in almost all parts of the world. A long tradition of utilization and an interesting chemical profile make this plant a fascinating and extensive object of study. The chemical profile also allows this plant to be used as a food and a pigment source in the food, pharmaceutical, and cosmetic industries. Previously conducted studies found phenolic acids and polyphenolic compounds in root, stalk, and stinging nettle leaves. Different extraction techniques were usually used to isolate them from the leaves. Obtained extracts were used to investigate biological activity further or formulate different functional food products. This study aimed to collect all available knowledge about this plant, its chemical composition, and biological activity and to summarize this knowledge with particular attention to polyphenolic compounds and the activity and mechanisms of their actions.


Assuntos
Urtica dioica , Urtica dioica/química , Extratos Vegetais/química , Fenóis/farmacologia , Fenóis/análise , Folhas de Planta/química , Alimento Funcional
20.
Polymers (Basel) ; 16(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38475266

RESUMO

The pull-out method was used to study the adhesive strength τ of "fiber-thermoset" systems with wide variations in area. Studied binders were based on resins that had different chemical natures (epoxy, epoxy phenol, orthophthalic, polyphenylsiloxane, and phenol-formaldehyde). Shear adhesive strength was determined for systems with two fiber types (glass and steel fibers). It was shown that strength τ depended on scale (area). Formation of τ occurred during the curing process and the system's subsequent cooling to the measurement temperature T. It was found that interface strength depended on measurement temperature across a wide temperature range that covered the highly elastic and the glassy state of the adhesive. The influence of residual stresses τres, acting at the "binder-fiber" interface, on the nature of the curves describing the dependence of the adhesive strength on the studied factor was experimentally shown. A qualitative explanation of the observed regularities is proposed.

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