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1.
Nature ; 600(7889): 506-511, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34649268

RESUMO

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Genoma Viral/genética , Genômica , SARS-CoV-2/genética , Substituição de Aminoácidos , COVID-19/transmissão , Inglaterra/epidemiologia , Monitoramento Epidemiológico , Humanos , Epidemiologia Molecular , Mutação , Quarentena/estatística & dados numéricos , SARS-CoV-2/classificação , Análise Espaço-Temporal , Glicoproteína da Espícula de Coronavírus/genética
2.
Mikrochim Acta ; 191(7): 413, 2024 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904692

RESUMO

Hepatocellular carcinoma (HCC) is the most common liver malignancy and is characterized by increasing incidence and high mortality rates. Current methods for the screening and diagnosis of HCC exhibit inherent limitations, highlighting the ever-growing need for the development of new methods for the early diagnosis of HCC. The aim of this work was to develop a novel electrochemical aptasensor for the detection of HepG2 cells, a type of circulating tumor cells that can be used as biomarkers for the early detection of HCC. A carbon screen-printed electrode was functionalized with a composite suspension containing graphene oxide, chitosan, and polyaniline nanoparticles to increase the electrode surface and provide anchoring sites for the HepG2 cell-specific aptamer. The aptamer was immobilized on the surface of the functionalized electrode using multipulse amperometry, an innovative technique that significantly reduces the time required for aptamer immobilization. The innovative platform was successfully employed for the first time for the amplification-free detection of HepG2 cells in a linear range from 10 to 200,000 cells/mL, with a limit of detection of 10 cells/mL. The platform demonstrated high selectivity and stability and was successfully used for the detection of HepG2 cells in spiked human serum samples with excellent recoveries.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Carcinoma Hepatocelular , Técnicas Eletroquímicas , Grafite , Neoplasias Hepáticas , Humanos , Células Hep G2 , Aptâmeros de Nucleotídeos/química , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/sangue , Técnicas Eletroquímicas/métodos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/sangue , Grafite/química , Técnicas Biossensoriais/métodos , Limite de Detecção , Compostos de Anilina/química , Eletrodos , Quitosana/química
3.
Drug Dev Ind Pharm ; 50(5): 446-459, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38622817

RESUMO

OBJECTIVE: The aim of the present study was to develop and optimize a wound dressing film loaded with chloramphenicol (CAM) and ibuprofen (IBU) using a Quality by Design (QbD) approach. SIGNIFICANCE: The two drugs have been combined in the same dressing as they address two critical aspects of the wound healing process, namely prevention of bacterial infection and reduction of inflammation and pain related to injury. METHODS: Three critical formulation variables were identified, namely the ratios of Kollicoat SR 30D, polyethylene glycol 400 and polyvinyl alcohol. These variables were further considered as factors of an experimental design, and 17 formulations loaded with CAM and IBU were prepared via solvent casting. The films were characterized in terms of dimensions, mechanical properties and bioadhesion. Additionally, the optimal formulation was characterized regarding tensile properties, swelling behavior, water vapor transmission rate, surface morphology, thermal behavior, goniometry, in vitro drug release, cell viability, and antibacterial activity. RESULTS: The film was optimized by setting minimal values for the folding endurance, adhesive force and hardness. The optimally formulated film showed good fluid handling properties in terms of swelling behavior and water vapor transmission rate. IBU and CAM were released from the film up to 80.9% and 82.5% for 8 h. The film was nontoxic, and the antibacterial activity was prominent against Micrococcus spp. and Streptococcus pyogenes. CONCLUSIONS: The QbD approach was successfully implemented to develop and optimize a novel film dressing promising for the treatment of low-exuding acute wounds prone to infection and inflammation.


Assuntos
Antibacterianos , Bandagens , Cloranfenicol , Ibuprofeno , Cicatrização , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Ibuprofeno/farmacologia , Cicatrização/efeitos dos fármacos , Cloranfenicol/administração & dosagem , Cloranfenicol/farmacologia , Cloranfenicol/química , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Liberação Controlada de Fármacos , Humanos , Álcool de Polivinil/química , Polietilenoglicóis/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica/métodos
5.
Medicina (Kaunas) ; 59(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36676728

RESUMO

Three ceramic and composite computer-aided design/computer-aided manufacturing (CAD/CAM) materials from different manufacturers (Cerasmart (CS)-nanoceramic resin; Straumann Nice (SN)-glass ceramic and Tetric CAD (TC)-composite resin) were tested to investigate the biocompatibility and sustainability on human fibroblasts and keratinocytes cells. Each type of CAD/CAM blocks restorative materials with fine and rough surfaces was exposed to an acidic environment for one month. After that, various powders were obtained by milling. In parallel, powders were also prepared from each restorative material, which were not exposed to the acidic environment. The cytotoxic effects were investigated by means of MTT and LDH assays, as well as nitric oxide production on two human normal cell lines, namely, fibroblasts (BJ) and keratinocytes (HaCaT). In addition, the degree of adhesion of fibroblast cells to each CAD/CAM material was evaluated by scanning electron microscopy (SEM). The results showed that the two samples that were exposed to an acidic environment (CS and SN) induced a reduction of mitochondrial activity and plasma membrane damage as regards the fibroblast cells. A similar effect was observed in TC_fine-exposed material, which seemed to induce necrosis at the tested concentration of 1 mg/mL. No oxidative stress was observed in fibroblasts and keratinocytes treated with the CAD/CAM materials. Regarding the adhesion degree, it was found that the fibroblasts adhere to all the occlusal veneers tested, with the mention that the CS and SN materials have a weaker adhesion with fewer cytoplasmic extensions than TC material. With all of this considered, the CAD/CAM restorative materials tested are biocompatible and represent support for the attachment and dispersion of cells.


Assuntos
Desenho Assistido por Computador , Humanos , Teste de Materiais , Propriedades de Superfície , Microscopia Eletrônica de Varredura
6.
Genome Res ; 27(10): 1730-1742, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28904015

RESUMO

In the era of genome-wide association studies (GWAS) and personalized medicine, predicting the impact of single nucleotide polymorphisms (SNPs) in regulatory elements is an important goal. Current approaches to determine the potential of regulatory SNPs depend on inadequate knowledge of cell-specific DNA binding motifs. Here, we present Sasquatch, a new computational approach that uses DNase footprint data to estimate and visualize the effects of noncoding variants on transcription factor binding. Sasquatch performs a comprehensive k-mer-based analysis of DNase footprints to determine any k-mer's potential for protein binding in a specific cell type and how this may be changed by sequence variants. Therefore, Sasquatch uses an unbiased approach, independent of known transcription factor binding sites and motifs. Sasquatch only requires a single DNase-seq data set per cell type, from any genotype, and produces consistent predictions from data generated by different experimental procedures and at different sequence depths. Here we demonstrate the effectiveness of Sasquatch using previously validated functional SNPs and benchmark its performance against existing approaches. Sasquatch is available as a versatile webtool incorporating publicly available data, including the human ENCODE collection. Thus, Sasquatch provides a powerful tool and repository for prioritizing likely regulatory SNPs in the noncoding genome.


Assuntos
Pegada de DNA/métodos , Desoxirribonucleases/química , Células Eritroides/metabolismo , Motivos de Nucleotídeos , Polimorfismo de Nucleotídeo Único , Elementos de Resposta , Análise de Sequência de DNA/métodos , Fatores de Transcrição/metabolismo , Humanos , Valor Preditivo dos Testes
7.
Sensors (Basel) ; 20(8)2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32325655

RESUMO

The detection of folic acid in biological samples or pharmaceutical products is of great importance due to its implications in the biological functions of the human body, along with the development and growth of the fetus. The deficiency of folic acid can be reversed by the intake of different pharmaceutical formulations or alimentary products fortified with this molecule. The elaboration of sensing platforms represents a continuous work in progress, a task in which the use of conductive polymers modified with different functionalities represents one of the outcoming strategies. The possibility of manipulating their morphology with the use of templates or surfactants represents another advantage. A sensing platform based on carboxylic functionalized polypyrrole was synthesized via the electrochemical approach in the presence of a polymeric surfactant on a graphite-based surface. The sensor was able to detect the folic acid from 2.5 µM to 200 µM with a calculated limited of detection of 0.8 µM. It was employed for the detection of the analyte from commercial human serum and pharmaceutical products with excellent recovery rates. The results were double checked using an optimized spectrophotometric procedure that confirmed furthermore the performances of the sensor related to real samples assessment.

8.
Molecules ; 25(4)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32070017

RESUMO

Medicinal plants are often used as reducing agents to prepare metal nanoparticles through green-synthesis due to natural compounds and their potential as chemotherapeutic drugs. Thus, three types of eco-friendly Ag-MnO2 nanoparticles (Ag-MnO2NPs) were synthesized using C. majus (CmNPs), V. minor (VmNPs), and a 1:1 mixture of the two extracts (MNPs). These NPs were characterized using S/TEM, EDX, XRD, and FTIR methods, and their biological activity was assessed in vitro on normal keratinocytes (HaCaT) and skin melanoma cells (A375). All synthesized NPs had manganese oxide in the middle, and silver oxide and plant extract on the exterior. The NPs had different forms (polygonal, oval, and spherical), uniformly distributed, with crystalline structures and different sizes (9.3 nm for MNPs; 10 nm for VmNPs, and 32.4 nm for CmNPs). The best results were obtained with VmNPs, which reduced the viability of A375 cells up 38.8% and had a moderate cytotoxic effect on HaCaT (46.4%) at concentrations above 500 µg/mL. At the same concentrations, CmNPs had a rather proliferative effect, whereas MNPs negatively affected both cell lines. For the first time, this paper proved the synergistic action of the combined C. majus and V. minor extracts to form small and uniformly distributed Ag-MnO2NPs with high potential for selective treatments.


Assuntos
Chelidonium/metabolismo , Compostos de Manganês/química , Nanopartículas Metálicas/química , Óxidos/química , Extratos Vegetais/metabolismo , Prata/química , Vinca/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Compostos de Manganês/farmacologia , Óxidos/farmacologia
9.
Molecules ; 25(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218110

RESUMO

Raman mapping is becoming a very useful tool in investigating cells and cellular components, as well as bioactive molecules intracellularly. In this study, we have encapsulated beta-carotene using a layer-by-layer technique, as a way to enhance its stability and bioavailability. Further, we have used Raman mapping to characterize the as-obtained capsules and monitor their uptake by the human retinal epithelial D407 cells. We were able to successfully map the beta-carotene distribution inside the capsules, to localize the capsules intracellularly, and distinguish between capsules and other cellular components.


Assuntos
Endocitose , Polieletrólitos/metabolismo , Análise Espectral Raman , beta Caroteno/metabolismo , Cápsulas , Linhagem Celular , Humanos , Análise de Componente Principal
10.
Molecules ; 24(22)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731755

RESUMO

Currently, research studies on nanoparticle cytotoxicity, uptake or internalization into the body's cells are of great interest for the improvement of diagnostic and therapeutic applications. We report here the synthesis and characterization of very stable novel warfarin-capped gold nanoparticles with an average diameter of 54 ± 10 nm which were prepared using sodium warfarin as a reducing agent. The nanoparticles were tested in terms of cytotoxicity and cellular internalization in vitro on two cell lines: normal lung fibroblast HFL-1 and human retinal pigment epithelial D407 cells. Our results showed that the normal lung fibroblast HFL-1 cells were more sensitive to the nanoparticle treatment compared to the human retinal pigment epithelial D407 cells. Moreover, any signs of potential cytotoxicity occurred during the first 24 h of treatment, the cellular viability remaining largely unchanged for longer exposure times. Transmission electron microscopy and dark field hyperspectral imaging revealed that the nanoparticles were effectively delivered and released to the HFL-1 and D407 cells' cytoplasm. Our results provide valuable information to further investigate sodium warfarin-capped gold nanoparticles for possible biological applications.


Assuntos
Citoplasma/metabolismo , Fibroblastos/metabolismo , Ouro , Nanopartículas Metálicas/química , Epitélio Pigmentado da Retina/metabolismo , Varfarina , Linhagem Celular , Fibroblastos/citologia , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Humanos , Epitélio Pigmentado da Retina/citologia , Varfarina/química , Varfarina/farmacocinética , Varfarina/farmacologia
11.
J Cell Physiol ; 231(4): 863-75, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26332160

RESUMO

Adult bone marrow mesenchymal stromal cells (BMSCs) can easily be differentiated into a variety of cells. In vivo transplantation of BMSCs-differentiated cells has had limited success, suggesting that these cells may not be fully compatible with the cells they are intended to replace in vivo. We investigated the structural and functional features of BMSCs-derived adipocytes as compared with adipocytes from adipose tissue, and the structure and functionality of lipid vesicles formed during BMSCs differentiation to adipocytes. Gas chromatography-mass spectrometry showed fatty acid composition of BMSCs-derived adipocytes and adipocytes from the adipose tissue to be very different, as is the lipid rafts composition, caveolin-1 expression, caveolae distribution in their membranes, and the pattern of expression of fatty acid elongases. Confocal microscopy confirmed the absence from BMSCs-derived adipocytes of markers of lipid droplets. BMSCs-derived adipocytes cannot convert deuterated glucose into deuterated species of fatty acids and cannot uptake the deuterated fatty acid-bovine serum albumin complexes from the culture medium, suggesting that intra-cellular accumulation of lipids does not occur by lipogenesis. We noted that BMSCs differentiation to adipocytes is accompanied by an increase in autophagy. Autophagic vesicles accumulate in the cytoplasm of BMSCs-derived adipocytes and their size and distribution resembles that of Nile Red-stained lipid vesicles. Stimulation of autophagy in BMSCs triggers the intra-cellular accumulation of lipids, while inhibition of autophagy prevents this accumulation. In conclusion, differentiation of BMSCs-derived adipocytes leads to intra-cellular accumulation of autophagic vesicles rather than functional lipid droplets, suggesting that these cells are not authentic adipocytes. J. Cell. Physiol. 231: 863-875, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Adipócitos/citologia , Autofagia , Diferenciação Celular , Vesículas Citoplasmáticas/metabolismo , Gotículas Lipídicas/metabolismo , Células-Tronco Mesenquimais/citologia , Acetiltransferases/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/citologia , Animais , Células da Medula Óssea/citologia , Cavéolas/metabolismo , Membrana Celular/metabolismo , Células Cultivadas , Deutério/metabolismo , Elongases de Ácidos Graxos , Ácidos Graxos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Glucose/metabolismo , Lipogênese , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/ultraestrutura , Ratos Sprague-Dawley
12.
Am J Physiol Heart Circ Physiol ; 310(11): H1702-14, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27059078

RESUMO

The blood-brain barrier (BBB) is the main interface controlling molecular and cellular traffic between the central nervous system (CNS) and the periphery. It consists of cerebral endothelial cells (CECs) interconnected by continuous tight junctions, and closely associated pericytes and astrocytes. Different parts of the CNS have diverse functions and structures and may be subject of different pathologies, in which the BBB is actively involved. It is largely unknown, however, what are the cellular and molecular differences of the BBB in different regions of the brain. Using in silico, in vitro, and ex vivo techniques we compared the expression of BBB-associated genes and proteins (i.e., markers of CECs, brain pericytes, and astrocytes) in the cortical grey matter and white matter. In silico human database analysis (obtained from recalculated data of the Allen Brain Atlas), qPCR, Western blot, and immunofluorescence studies on porcine and mouse brain tissue indicated an increased expression of glial fibrillary acidic protein in astrocytes in the white matter compared with the grey matter. We have also found increased expression of genes of the junctional complex of CECs (occludin, claudin-5, and α-catenin) in the white matter compared with the cerebral cortex. Accordingly, occludin, claudin-5, and α-catenin proteins showed increased expression in CECs of the white matter compared with endothelial cells of the cortical grey matter. In parallel, barrier properties of white matter CECs were superior as well. These differences might be important in the pathogenesis of diseases differently affecting distinct regions of the brain.


Assuntos
Barreira Hematoencefálica/metabolismo , Moléculas de Adesão Celular/metabolismo , Córtex Cerebral/metabolismo , Substância Cinzenta/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Receptores de Fatores de Crescimento/metabolismo , Proteínas de Junções Íntimas/metabolismo , Substância Branca/metabolismo , Animais , Astrócitos/metabolismo , Simulação por Computador , Feminino , Humanos , Masculino , Camundongos , Estrutura Molecular , Pericitos/metabolismo , Suínos , Junções Íntimas/metabolismo
13.
Histochem Cell Biol ; 146(2): 153-65, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27085705

RESUMO

The development of thymocytes and generation of mature T cells is a complex process that requires spatio-temporal interactions of thymocytes with the other cells of the thymus microenvironment. Recently, mesenchymal stromal cells were isolated from the neonatal human thymus and differentiated into chondrogenic, osteogenic, and adipogenic lineages, just like their bone marrow counterparts. However, their function in thymocyte homeostasis is unknown. In our autologous co-cultures of rat mesenchymal stromal cells and thymocytes, the stromal cells preserve the viability of cultured thymocytes and stimulate the development of CD4-CD8- double-negative and the maturation of mainly CD4+ single-positive thymocytes. Thymocytes also influence the stemness of bone marrow mesenchymal stromal cells, as their expression of CD44, a marker associated with cellular proliferation and migration, is reduced in co-cultures. Mesenchymal stromal cells' influence on thymocyte development requires direct physical contact between the two cells and is not mediated by a soluble factor. When the two types of cells were physically separated, the stimulative effects of mesenchymal stromal cells on thymocytes did not occur. Electron microscopy confirmed the close contact between the membranes of thymocytes and mesenchymal stromal cells. Our experiments suggest that membrane exchanges could occur between mesenchymal stromal cells and thymocytes, such as the transfer of CD44 from mesenchymal stromal cells to the thymocytes, but its functional significance for thymocytes development remains to be established. These results suggest that mesenchymal stromal cells could normally be a part of the in vivo thymic microenvironment and form a niche that could sustain and guide the development of thymocytes.


Assuntos
Adesão Celular , Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Timócitos/citologia , Animais , Sobrevivência Celular , Técnicas de Cocultura , Feminino , Citometria de Fluxo , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Microscopia Confocal , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley , Timócitos/metabolismo
14.
Animals (Basel) ; 14(12)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38929396

RESUMO

The purpose of this study was to analyze the ultrastructure of the testes of sexually immature calves and reproductive bulls of the Polish Holstein-Friesian Black-and-White breed. Utilizing TEM, this study identified three distinct stages of seminiferous tubule development in calves, characterized by varying shapes, distributions, and arrangements of individual cells. In immature animals, early developing spermatocytes, prespermatogonia, and pre-Sertoli cells were observed within the seminiferous tubules. In sexually mature bulls, all cells of the spermatogenic series were observed, situated on a thin, multilayered basal lamina, which forms characteristic undulations. An abundant smooth endoplasmic reticulum was observed in the cytoplasm of spermatogonia in both groups of animals, forming characteristic membranous swirls. In adult bulls, spermatogonia maintain contact with each other through numerous cytoplasmic bridges and cell connections, forming small spaces with visible microvilli between them. The ultrastructural analysis facilitated the identification of morphological changes occurring during the maturation of pre-Sertoli cells, transitioning from a large euchromatic nucleus to a nucleus in which the formation of characteristic vesicles and tubules could be observed. It should also be emphasized that two types of Sertoli cells, namely dark and light electron-dense cells, can be found in cattle. These cells differ from each other, indicating that they may perform different functions. The widespread recognition of the presence of two types of Sertoli cells in cattle will undoubtedly contribute to a better understanding of the processes occurring within the testes and provide a basis for further research in this area.

15.
Pharmacy (Basel) ; 12(2)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38668094

RESUMO

In Tunisia, self-medication is a common practice, and there is a continual rise in the prevalence of cardiovascular disease. Given the lack of data on the self-medication practices (SMPs) among cardiovascular patients in this area, the present study aimed to identify the prevalence and determinants of SMPs among cardiovascular patients in the city of Béja. A community-pharmacy-based survey was conducted among selected cardiovascular patients in Béja, Tunisia, from May 2021 to June 2021. Data were collected using a self-administered questionnaire provided by pharmacists during in-person surveys with patients. Descriptive statistics were used to summarize the data, while Fisher's exact test was used for categorical variables, with the significance level set at p < 0.05. The frequency of self-medication among the 150 respondents was 96%; 70.14% of participants reported that the primary reason why people engage in self-medication is the existence of an old prescription. The most prevalent conditions leading patients to self-medicate were headaches (100%), fever (83.33%), toothache (65.97%), and dry cough (47.92%). The most frequently self-administered drugs were paracetamol (100%), antibiotics (56.94%), and antitussives (47.92%). The results of our study indicate that SMPs among Tunisian cardiovascular patients have a high prevalence. With this in mind, healthcare practitioners should ask their patients about their self-medication practices and advise cardiovascular patients about the risks and benefits associated with this practice.

16.
Pharmaceutics ; 15(3)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36986870

RESUMO

A biogenic carrier for 5-fluorouracil (5-FU) loading and subsequent tableting as a new drug formulation for slow release has been proposed using the biomineral from blue crab carapace. Due to its highly ordered 3D porous nanoarchitecture, the biogenic carbonate carrier could achieve increased effectiveness in colorectal cancer cure provided that the formulation would successfully pass through the gastric acid conditions. Following the recently proven viability of the concept by demonstrating the slow release of the drug from the carrier using the highly sensitive SERS technique, here we investigated the 5-FU release from the composite tablet drug in pH conditions replicating the gastric environment. The released drug from the tablet was studied in solutions with three relevant pH values, pH 2, pH 3, and pH 4. The 5-FU SERS spectral signature for each pH value was used to build calibration curves for quantitative SERS analysis. The results suggested a similarly slow-releasing pattern in acid pH environments to that in neutral conditions. Although biogenic calcite dissolution was expected in acid conditions, the X-ray diffraction and Raman spectroscopy showed preservation of calcite mineral along with the monohydrocalcite during acid solution exposure for two hours. The total released amount in a time course of seven hours, however, was lower in acidic pH solutions, with a maximum fraction of ~40% of the total amount of loaded drug, for pH 2, as opposed to ~80% for neutral values. Nonetheless, these results clearly prove that the novel composite drug retains its slow-releasing character in environmental conditions compatible with the gastrointestinal pH and that it is a viable and biocompatible alternative for oral delivery of anticancer drug to reach the lower gastro-intestinal tract.

17.
ACS Omega ; 8(17): 14952-14964, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37151495

RESUMO

In this study, three different morphologies, nanoflower (NF), nano sponge (NS), and nano urchin (NU), of zinc oxide (ZnO) nanostructures were synthesized successfully via a mild hydrothermal method. After synthesis, the samples were annealed in the atmosphere at 300, 600, and 800 °C. Although annealing provides different degradation kinetics for different morphologies, ZnO NS performed significantly better than other morphologies for all annealing temperatures we used in the study. When the photoluminescence, electron paramagnetic resonance spectroscopy, BET surface, and X-ray diffraction analysis results are examined, it is revealed that the defect structure, pore diameter, and crystallinity cumulatively affect the photocatalytic activity of ZnO nanocatalysts. As a result, to obtain high photocatalytic activity in rhodamine B (RhB) degradation, it is necessary to develop a ZnO catalyst with fewer core defects, more oxygen vacancies, near band emission, large crystallite size, and large pore diameter. The ZnO NS-800 °C nanocatalyst studied here had a 35.6 × 10-3 min-1 rate constant and excellent stability after a 5-cycle photocatalytic degradation of RhB.

18.
Pharmaceuticals (Basel) ; 16(6)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37375800

RESUMO

Pharmacological responses vary by sex in several illnesses. This narrative review summarizes sex variations in pharmaceutical response in SARS-CoV-2 infection, dyslipidemia, and diabetes mellitus. Infection with SARS-CoV-2 is more severe and deadly in men than women. This may be attributed to immunological responses, genetics, and hormones. Some research shows that men may respond better to genomic vaccinations and females to antiviral medications such as remdesivir (Moderna and Pfizer-BioNTech). In dyslipidemia, women tend to have greater HDL-C and lower LDL-C than men. Some studies show that females may need lower statin dosages than men to obtain equal LDL-C reductions. Ezetimibe co-administered with a statin significantly improved lipid profile indicators in men compared to women. Statins reduce dementia risk. Atorvastatin decreased dementia risk in males (adjusted HR 0.92, 95% CI 0.88-0.97), whereas lovastatin lowered dementia risk in women (HR 0.74, 95% CI 0.58-0.95). In diabetes mellitus, evidence suggests that females may have a higher risk of developing certain complications such as diabetic retinopathy and neuropathy, despite having lower rates of cardiovascular disease than males. This could be the result of differences in hormonal influences and genetic factors. Some research shows females may respond better to oral hypoglycemic medications such as metformin. In conclusion, sex-related differences in pharmacological response have been observed in SARS-CoV-2 infection, dyslipidemia, and diabetes mellitus. Further research is needed to better understand these differences and to develop personalized treatment strategies for males and females with these conditions.

19.
Microorganisms ; 11(3)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36985318

RESUMO

Bacterial infections are a major concern as antibiotic resistance poses a great threat, therefore leading to a race against time into finding new drugs or improving the existing resources. Nanomaterials with high surface area and bactericidal properties are the most promising ones that help combating microbial infections. In our case, graphene decorated with silver nanoparticles Gr-Ag (5 wt% Ag) exhibited inhibitory capacity against S. aureus and E. coli. The newly formed hybrid material was next incubated with high-efficiency particulate air (HEPA) filter, to obtain one with bactericidal properties. The modified filter had greater inhibitory action against the tested strains, compared to the control, and the effect was better against the Gram-negative model. Even if the bacteria remained attached to the filters, their colony forming unit capacity was affected by the Gr-Ag (5 wt% Ag) hybrid material, when they were subsequently re-cultured on fresh agar media. Therefore, the HEPA filter modified with Gr-Ag (5 wt% Ag) has high antibacterial properties that may substantially improve the existing technology.

20.
Ther Deliv ; 14(2): 157-173, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-37158273

RESUMO

Silica nanoparticles (SiO2) are increasingly investigated for biomedical applications. Aim: This study aimed to analyze the potential use of a SiO2 nanoparticles coated with biocompatible polydopamine (SiO2@PDA) as a potential chemotherapeutic drug carrier. Materials & methods: SiO2 morphology and PDA adhesion was analyzed by dynamic light scattering, electron microscopy and nuclear magnetic resonance. Cytotoxicity studies and morphology analyses (immunofluorescence, scanning and transmission electron microscopy) were used to assess the cellular reaction to the SiO2@PDA nanoparticles and to identify a biocompatible (safe use) window. Results & conclusion: Concentrations above 10 µg/ml and up to 100 µg/ml SiO2@PDA showed the best biocompatibility on human melanoma cells at 24 h and represent a potential drug carrier template for targeted melanoma cancer treatment.


Tiny particles can be small enough to enter cells. This is why they may be useful in the treatment of cancer. We made particles in a way that is friendly for human cells, then we analyzed their effects on cancer cells. Our tests showed that these particles could be useful for treatment because they do not worsen cancer cells. This is important because sometimes after treatment, cancer cells can become more dangerous. This way, even if the drug did not work, the cancer will not worsen.


Assuntos
Melanoma , Nanopartículas , Humanos , Portadores de Fármacos , Dióxido de Silício , Melanoma/tratamento farmacológico
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