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1.
Nanomedicine ; 53: 102704, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37582426

RESUMO

Glioblastoma (GBM) is the most prevalent malignant primary brain tumor and currently lacks an effective treatment. In this study, we utilized a microfluidic system to synthesize docosahexaenoic acid (DHA) liposomes for GBM therapy. DHA is an omega-3 (ω3) polyunsaturated fatty acid commonly found in human dietary consumption that has demonstrated potential in mitigating cancer development. The microfluidic device employed allowed for precise fine-tuning of the physicochemical properties of liposomes by adjusting the flow rate ratios, flow rates, and lipid concentrations. Three distinct-sized liposomes, ranging from 80 nm and 130 nm, were successfully internalized by GBM cells, and demonstrated the ability to reduce the viability of these cells. Furthermore, DHA liposomes proved significantly more efficient in triggering apoptotic pathways, through caspase-3-dependent mechanisms, in comparison to free DHA. Thus, the nanomedicine platform established in this study presents new opportunities in the development of liposome formulations incorporating ω3 fatty acids for cancer therapy.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Lipossomos/química , Ácidos Docosa-Hexaenoicos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Microfluídica , Neoplasias Encefálicas/patologia
2.
Nanomedicine ; 49: 102663, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36773669

RESUMO

Glioblastoma (GBM) is a highly aggressive malignant brain tumor currently without an effective treatment. Inspired by the recent advances in cell membrane biomimetic nanocarriers and by the key role of macrophages in GBM pathology, we developed macrophage membrane liposomes (MML) for GBM targeting. For the first time, it was assessed the role of macrophage polarization states in the effectiveness of these drug delivery systems. Interestingly, we observed that MML derived from M2 macrophages (M2 MML) presents higher uptake and increased delivery of the anticarcinogenic drug doxorubicin compared to M1 macrophage-derived nanocarriers (M1 MML) and control liposomes (CL). Moreover, the lowest uptake by macrophages of MML reveals promising immune escaping properties. Notably, M2 macrophages unveiled a higher expression of integrin CD49d, a crucial protein involved in the bilateral communication of macrophages with tumor cells. Therefore, our findings suggest the potential of using M2 macrophage membranes to develop novel nanocarriers targeting GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Lipossomos/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Biomimética , Macrófagos/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Membrana Celular/metabolismo , Linhagem Celular Tumoral , Microambiente Tumoral
3.
Int J Immunogenet ; 44(2): 51-61, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28266165

RESUMO

Atopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13). Interleukin-33 (IL-33) appears to be a potent inducer of Th2 immune response. This occurs when IL-33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation. Polymorphisms in the IL33 and IL1RL1 can act as protective or risk factors for asthma and/or allergy in humans. No study was conducted to replicate such findings in a European and African descendent mixed population. DNA was extracted from peripheral blood from 1223 subjects, and the samples were genotyped using Illumina 2.5 Human Omni Beadchip. We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL-5 and IL-13 production and skin prick test (SPT). Logistics regressions were performed using PLINK software 1.07. The analyses were adjusted for sex, age, helminth infection and ancestry markers. The G allele of IL33 SNP rs12551256 was negatively associated with asthma (OR 0.71, 95% CI: 0.53-0.94, P = 0.017). In contrast, the A allele of IL1RL1 rs1041973 was positively associated with IL-5 production (OR 1.36, 95% CI: 1.09-1.84, P = 0.044), sIgE levels (OR 1.40, 95% CI: 1.07-1.84, P = 0.013) and positive SPT (OR 1.48, 95% CI: 1.08-2.03, P = 0.014), for Blomia tropicalis mite. The same allele, in atopic subjects, was associated with decreased production of soluble ST2 (sST2) (P < 0.05). Moreover, expression quantitative trait loci (eQTL) analysis suggests that rs1041973 and rs873022 regulate the expression of IL1RL1 gene. This latest SNP, rs873022, the T allele, was also associated with a lower production of sST2 in plasma of Brazilians. The genetic risk score for rs1041973 and rs16924161 demonstrated a higher risk for SPT positivity against B. tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma.


Assuntos
Asma/genética , Estudos de Associação Genética , Hipersensibilidade/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Interleucina-33/genética , Animais , Asma/sangue , Asma/microbiologia , Asma/patologia , Brasil , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/microbiologia , Hipersensibilidade Imediata/genética , Imunoglobulina E/sangue , Interleucina-5/genética , Masculino , Ácaros/imunologia , Ácaros/patogenicidade , Polimorfismo de Nucleotídeo Único , Pele/imunologia , Pele/microbiologia , Células Th2
4.
Biomed Microdevices ; 16(1): 69-78, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24122322

RESUMO

The use of bottom-up approaches in tissue engineering applications is advantageous since they enable the combination of various layers that could be made from different materials and/or incorporate different biochemical cues. Regarding the complex structure and the vascular system of the bone tissue, the aim of this study was to develop an innovative bottom-up approach that allows the construction of 3D biodegradable scaffolds from 2D microfabricated membranes with precise shape, pore size and porosity. For that purpose, poly (caprolactone) (PCL) and starch ­ poly (caprolactone) (SPCL (30 % starch)) blended sheets were used as substrates to produce the microfabricated membranes using micro hotembossing. The use of this micro fabrication process allowed accurately imprinting micropillars and microholes in reproducible way. The assembling of the microfabricated membranes was performed using an easy, highly reproducible and inexpensive approach based on its successive stacking. Additionaly, the suitability of the microfabricated membranes to support the attachment and the cytoskeletal organization of human bone marrow stem cells (hBMSCs), macrovascular endothelial cells and osteoblasts derived from hBMSCs was demonstrated. Furthermore, hBMSCs proliferated and maintained the expression of the stromal progenitor marker STRO-1 when cultured on both PCL and SPCL microfabricated membranes. The proposed methodology constitutes a promising alternative to the traditional processing methods used to prepare tissue engineering scaffolds.


Assuntos
Osso e Ossos/química , Microtecnologia/métodos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Adesão Celular , Diferenciação Celular , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana , Humanos , Imuno-Histoquímica , Células-Tronco Mesenquimais/química , Microscopia Eletrônica de Varredura , Osteoblastos/química , Polímeros/química , Porosidade
5.
Parasite Immunol ; 35(5-6): 188-93, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23398517

RESUMO

Infections with Trichuris trichiura and other trichurid nematodes have been reported to display protective effects against atopy, allergic and autoimmune diseases. The aims of the present study were to investigate the immunomodulatory properties of T. trichiura adult worm extract (TtE) and its fractions (TtEFs) on the production of cytokines by peripheral blood mononuclear cells and to identify their proteinaceous components. Fourteen TtEFs were obtained by ion exchange chromatography and tested for effects on cytokine production by peripheral blood mononuclear cells. The molecular constituents of the six most active fractions were evaluated using nano-LC/mass spectrometry. The homology between T. trichiura and the related nematode Trichinella spiralis was used to identify 12 proteins in TtEFs. Among those identified, fructose biphosphate aldolase, a homologue of macrophage migration inhibitory factor and heat-shock protein 70 may contribute to the immunomodulatory effects of TtEFs. The identification of such proteins could lead to the development of novel drugs for the therapy of allergic and other inflammatory diseases.


Assuntos
Citocinas/sangue , Proteínas de Helminto/imunologia , Leucócitos Mononucleares/imunologia , Trichuris/imunologia , Adulto , Animais , Criança , Cromatografia por Troca Iônica , Frutose-Bifosfato Aldolase/química , Frutose-Bifosfato Aldolase/imunologia , Proteínas de Choque Térmico HSP70/imunologia , Proteínas de Helminto/química , Humanos , Proteômica , Trichinella spiralis/química , Tricuríase/imunologia , Tricuríase/parasitologia , Trichuris/química , Adulto Jovem
6.
Bioact Mater ; 28: 337-347, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37519922

RESUMO

Surface topographies of cell culture substrates can be used to generate in vitro cell culture environments similar to the in vivo cell niches. In vivo, the physical properties of the extracellular matrix (ECM), such as its topography, provide physical cues that play an important role in modulating cell function. Mimicking these properties remains a challenge to provide in vitro realistic environments for cells. Artificially generated substrates' topographies were used extensively to explore this important surface cue. More recently, the replication of natural surface topographies has been enabling to exploration of characteristics such as hierarchy and size scales relevant for cells as advanced biomimetic substrates. These substrates offer more realistic and mimetic environments regarding the topographies found in vivo. This review will highlight the use of natural surface topographies as a template to generate substrates for in-vitro cell culture. This review starts with an analysis of the main cell functions that can be regulated by the substrate's surface topography through cell-substrate interactions. Then, we will discuss research works wherein substrates for cell biology decorated with natural surface topographies were used and investigated regarding their influence on cellular performance. At the end of this review, we will highlight the advantages and challenges of the use of natural surface topographies as a template for the generation of advanced substrates for cell culture.

7.
Biomed Mater ; 18(3)2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36930979

RESUMO

The interaction between cells and biomaterials is essential for the success of biomedical applications in which the implantation of biomaterials in the human body is necessary. It has been demonstrated that material's chemical, mechanical, and structural properties can influence cell behaviour. The surface topography of biomaterials is a physical property that can have a major role in mediating cell-material interactions. This interaction can lead to different cell responses regarding cell motility, proliferation, migration, and even differentiation. The combination of biomaterials with mesenchymal stem cells (MSCs) for bone regeneration is a promising strategy to avoid the need for autologous transplant of bone. Surface topography was also associated with the capacity to control MSCs differentiation. Most of the topographies studied so far involve machine-generated surface topographies. Herein, our strategy differentiates from the above mentioned since we selected natural surface topographies that can modulate cell functions for regenerative medicine strategies.Rubus fruticosusleaf was the selected topography to be replicated in polycaprolactone (PCL) membranes through polydimethylsiloxane moulding and using soft lithography. Afterwards, rat bone marrow stem cells (rBMSCs) were seeded at the surface of the imprinted PCL membranes to characterize the bioactive potential of our biomimetic surface topography to drive rBMSCs differentiation into the osteogenic lineage. The selected surface topography in combination with the osteogenic inductive medium reveals having a synergistic effect promoting osteogenic differentiation.


Assuntos
Biomimética , Osteogênese , Ratos , Humanos , Animais , Diferenciação Celular , Materiais Biocompatíveis/farmacologia , Osso e Ossos
8.
Biomater Adv ; 141: 213128, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36179494

RESUMO

The implantation of biomaterial devices can negatively impact the local microenvironment through several processes including the injury incurred during the implantation process and the associated host inflammatory response. Immune cell responses to implantable biomaterial devices mediate host-material interactions. Indeed, the immune system plays a central role in several biological processes required for the integration of biomaterials such as wound healing, tissue integration, inflammation, and foreign body reactions. The implant physicochemical properties such as size, shape, surface area, topography, and chemistry have been shown to provide cues to the immune system. Its induced immune-modulatory responses towards inflammatory or wound healing phenotypes can determine the success of the implant. In this work, we aim to evaluate the impact of some biomimetic surface topographies on macrophages' acute inflammatory response. For that, we selected 4 different biological surfaces to replicate through soft lithography on spin casting PCL membranes. Those topographies were: the surface of E. coli, S.eppidermidis and L929 cells cultured in polystyrene tissue culture disks, and an Eggshell membrane. We selected a model based on THP-1-derived macrophages to study the analysis of the expression of both pro-inflammatory and anti-inflammatory markers. Our results revealed that depending on the surface where these cells are seeded, they present different phenotypes. Macrophages present a M1-like phenotype when they are cultured on top of PCL membranes with the surface topography of E. coli and S. epidermidis. When cultured on membranes with L929 monolayers or Eggshell membrane surface topography, the macrophages present a M2-like phenotype. These results can be a significant advance in the development of new implantable biomaterial devices since they can help to modulate the inflammatory responses to implanted biomaterials by controlling their surface topography.


Assuntos
Materiais Biocompatíveis , Poliestirenos , Anti-Inflamatórios/química , Materiais Biocompatíveis/efeitos adversos , Biomimética , Escherichia coli , Humanos , Inflamação/metabolismo , Macrófagos , Poliestirenos/química
9.
J Drug Target ; 30(8): 873-883, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35414285

RESUMO

Effective and safe therapies to counteract persistent inflammation are necessary. We developed erythrocyte-derived liposomes (EDLs) with intrinsic anti-inflammatory activity. The EDLs were prepared using lipids extracted from erythrocyte membranes, which are rich in omega-3 fatty acids with several health benefits. Diclofenac, a widely used anti-inflammatory drug, was incorporated into EDLs in relevant therapeutic concentrations. The EDLs were also functionalised with folic acid to allow their active targeting of M1 macrophages, which are key players in inflammatory processes. In the presence of lipopolysaccharide (LPS)-stimulated macrophages, empty EDLs and EDLs incorporating diclofenac were able to reduce the levels of important pro-inflammatory cytokines, namely interleukin-6 (IL-6; ≈85% and 77%, respectively) and tumour necrosis factor-alpha (TNF-α; ≈64% and 72%, respectively). Strikingly, cytocompatible concentrations of EDLs presented similar effects to dexamethasone, a potent anti-inflammatory drug, in reducing IL-6 and TNF-α concentrations, demonstrating the EDLs potential to be used as bioactive carriers in the treatment of inflammatory diseases.


Assuntos
Lipossomos , Fator de Necrose Tumoral alfa , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas , Diclofenaco/farmacologia , Diclofenaco/uso terapêutico , Eritrócitos , Humanos , Inflamação/tratamento farmacológico , Interleucina-6
10.
Trop Med Int Health ; 16(4): 514-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21410848

RESUMO

OBJECTIVE: To investigate the association between Toxocara canis infection and total IgE levels and eosinophilia in blood donors from a large Brazilian city. METHODS: Two hundred and sixty-eight blood donors from a government blood bank were tested. No helminth infection was diagnosed by parasitological stool examination. Total IgE levels and T. canis infection status were determined by ELISA. Eosinophil levels were determined using an automatic blood cell counter. RESULTS: Toxocara canis IgG antibodies were found in 124 (46.3%); 102 (38.0%) had eosinophilia ≥4% and 29 (10.8%) had eosinophilia ≥10%, respectively; 140 (52.2%) individuals had total IgE antibodies above the cut-off levels. Both total IgE and eosinophil levels ≥10% were positively associated with the infection. CONCLUSION: This study revealed a high prevalence of T. canis infection in blood donors, highlighting the need for screening for this infection. It also demonstrated that this population otherwise healthy has higher levels of blood eosinophils and total IgE and that both parameters are associated with T. canis infection.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Eosinofilia/parasitologia , Imunoglobulina E/sangue , Toxocara canis , Toxocaríase/complicações , Adulto , Animais , Anticorpos Anti-Helmínticos/sangue , Bancos de Sangue , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Toxocara canis/imunologia , Toxocaríase/epidemiologia , Toxocaríase/imunologia
11.
Colloids Surf B Biointerfaces ; 206: 111910, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34147929

RESUMO

The development of bioresponsive interfaces that can induce a beneficial impact on cell mechanisms, such as adhesion, proliferation, migration and differentiation are of utmost relevance in Tissue engineering (TE) approaches. The surface topography is a captivating property that contribute to interesting cell responses, being inspired by several cues found in nature. Therefore, the study herein presented reports the fabrication of a surface topography using the Rubus fruticosus leaf on spin casting polycaprolactone (PCL) membranes. The topography was replicated by replica molding rapid fabrication technique and nanoimprint lithography (NIL). The biomimetic patterned PCL membranes (bpM) were successfully produced revealing high detail due to the complexity of the leaf's surface ranging from the stroma structures to nerves structures. The thermal evaluation revealed a slight increase of crystallinity of the bpM compared with the other tested conditions. However, did not induce significant effects on the melting and recrystallization temperatures. The mechanical properties revealed that the young modulus increase from 3.2 MPa to 4.4 MPa during the imprinting process. However, bpM presents a lowest elongation capacity than bare membrane (bM) (1076 to 444 %, respectively) due to the heterogeneous thickness induced by the topography. The selected topography revealed to promote a positive bioresponse, depicted by the improvement of the cellular behaviour and different organization. This promising strategy revealed that circumventing the traditional topographies by nature mimetic topographies is fundamental for the development of innovative bioresponsive substrates that can tune cellular behaviour in TE strategies.


Assuntos
Biomimética , Rubus , Folhas de Planta , Propriedades de Superfície , Engenharia Tecidual
12.
J Control Release ; 337: 482-493, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34352316

RESUMO

In the last two decades no significant advances were achieved in the treatment of the most frequent and malignant types of brain tumors. The main difficulties in achieving progress are related to the incapacity to deliver drugs in therapeutic amounts into the central nervous system and the associated severe side effects. Indeed, to obtain effective treatments, the drugs should be able to cross the intended biological barriers and not being inactivated before reaching the specific therapeutic target. To overcome these challenges the development of synthetic nanocarriers has been widely explored for brain tumor treatment but unfortunately with no clinical translation until date. The use of cell-derived nanocarriers or biomimetic nanocarriers has been studied in the last few years, considering their innate bio-interfacing properties. The ability to carry therapeutic agents and a higher selectivity towards brain tumors would bring new hope for the development of safe and effective treatments. In this review, we explore the biological barriers that need to be crossed for effective delivery in brain tumors, and the types and properties of cell-based nanocarriers (extracellular vesicles and cell-membrane coated nanocarriers) currently under investigation.


Assuntos
Neoplasias Encefálicas , Nanopartículas , Biomimética , Neoplasias Encefálicas/tratamento farmacológico , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos
13.
Biomacromolecules ; 11(12): 3228-36, 2010 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-21105638

RESUMO

Mesenchymal stem cells (MSCs) have been recognized for their ability to differentiate into cells of different tissues such as bone, cartilage, or adipose tissue, and therefore are of great interest for potential therapeutic strategies. Adherent, colony-forming, fibroblastic cells were isolated from human bone marrow aspirates, from patients undergoing knee arthroplasties, and the MSCs phenotype characterized by flow cytometry. Afterward, cells were seeded onto electrospun polycaprolactone nanofiber meshes and cultured in a multichamber flow perfusion bioreactor to determine their ability to produce cartilagineous extracellular matrix. Results indicate that the flow perfusion bioreactor increased the chondrogenic differentiation of hBM-MSCs, as confirmed either by morphological and RT-PCR analysis. Cartilage-related genes such as aggrecan, collagen type II, and Sox9 were expressed. ECM deposition was also detected by histological procedures. Collagen type II was present in the samples, as well as collagen type I. Despite no statistically significant values being obtained for gene expression, the other results support the choice of the bioreactor for this type of culture.


Assuntos
Cartilagem/citologia , Células-Tronco Mesenquimais/citologia , Nanofibras/química , Engenharia Tecidual/métodos , Reatores Biológicos , Diferenciação Celular , Células Cultivadas , Colágeno Tipo I , Colágeno Tipo II , Fibroblastos/citologia , Humanos , Poliésteres
14.
Protein Expr Purif ; 63(2): 89-94, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18950713

RESUMO

Bone morphogenetic proteins (BMPs) are cytokines from the TGF-beta superfamily, with important roles during embryonic development and in the induction of bone and cartilage tissue differentiation in the adult body. In this contribution, we report the expression of recombinant human BMP-4, BMP-9, BMP-10, BMP-11 (or growth differentiation factor-11, GDF-11) and BMP-14 (GDF-5), using Escherichia coli pET-25b vector. BMPs were overexpressed, purified by affinity his-tag chromatography and shown to induce the expression of early markers of bone differentiation (e.g. smad-1, smad-5, runx2/cbfa1, dlx5, osterix, osteopontin, bone sialoprotein and alkaline phosphatase) in C2C12 cells and in human adipose stem cells. The described approach is a promising method for producing large amounts of different recombinant BMPs that show potential for novel biomedical applications.


Assuntos
Células-Tronco Adultas/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/biossíntese , Proteínas Morfogenéticas Ósseas/farmacologia , Osteogênese , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/farmacologia , Células-Tronco Adultas/metabolismo , Animais , Biomarcadores/metabolismo , Proteínas Morfogenéticas Ósseas/isolamento & purificação , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Proteínas Recombinantes/isolamento & purificação
15.
Clin Exp Allergy ; 38(11): 1769-77, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18547322

RESUMO

BACKGROUND: Allergic diseases cause a large and increasing burden in developed countries and in urban centres in middle-income countries. The causes of this increase are unknown and, currently, there are no interventions to prevent the development of allergic diseases. The 'hygiene hypothesis' has tried to explain the increase through a reduction in the frequency of childhood infections causing a failure to program the immune system for adequate immune regulation. Intestinal helminth parasites are prevalent in childhood in developing countries and are associated with a lower prevalence of allergen skin test reactivity and asthma. OBJECTIVES: To investigate whether children who had intestinal helminth infections during early childhood have a lower prevalence of allergen skin test reactivity later in childhood. METHODS: We re-visited a population of 1055 children from whom stool samples had been collected for detection of intestinal helminth infections for another study, and collected new stool samples and performed allergen skin prick testing. Information on potential confounding variables was collected. RESULTS: Children with heavy infections with Trichuris trichiura in early childhood had a significantly reduced prevalence of allergen skin test reactivity in later childhood, even in the absence of T. trichiura infection at the time of skin testing in later childhood. CONCLUSION: Early heavy infections with T. trichiura may protect against the development of allergen skin test reactivity in later childhood. Novel treatments to program immune-regulation in early childhood in a way that mimics the effects of early infections with T. trichiura may offer new strategies for the prevention of allergic disease.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Imediata/etiologia , Tricuríase/imunologia , Trichuris/imunologia , Animais , Antígenos de Helmintos/imunologia , Ascaríase/epidemiologia , Ascaríase/imunologia , Ascaris lumbricoides/isolamento & purificação , Criança , Pré-Escolar , Fezes/parasitologia , Feminino , Helmintíase/epidemiologia , Helmintíase/imunologia , Infecções por Uncinaria/epidemiologia , Infecções por Uncinaria/imunologia , Humanos , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/imunologia , Lactente , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/imunologia , Masculino , Razão de Chances , Testes Cutâneos , Tricuríase/epidemiologia , Trichuris/isolamento & purificação
16.
J Ethnopharmacol ; 119(1): 41-6, 2008 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-18588965

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The bee pollen is used in folk medicine to alleviate allergic reactions. The bee pollen phenolic extract (BPPE) consists in phenolic compounds (flavonoids) from plants picked by Apis mellifera bee. AIM OF THIS STUDY: Here we evaluated the anti-allergic property of the BPPE and the flavonoid myricetin (MYR) in murine model of ovalbumin (OVA)-induced allergy. MATERIALS AND METHODS: The study focused on the BPPE or myricetin treatment of OVA-sensitized BALB/c mice and their effects on the IgE and IgG1 production, pulmonary cell migration, eosinophil peroxidase (EPO) activity and anaphylactic shock reaction. RESULTS: The BPPE treatment (200mg/kg) showed inhibition of the paw edema, IgE and IgG(1) OVA-specific production, leukocyte migration to the bronchoalveolar lavage (BAL) and EPO activity in lungs. In addition, BPPE treatment showed partial protection on the anaphylactic shock reaction induced by OVA. Treatment with myricetin (5 mg/kg) also inhibited pulmonary cell migration and IgE and IgG(1) OVA-specific production. CONCLUSIONS: These results support the hypothesis the myricetin is one of the flavonoids of BPPE responsible for the anti-allergic effect and a potential tool to treat allergies.


Assuntos
Antialérgicos/farmacologia , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Pólen/química , Anafilaxia/tratamento farmacológico , Anafilaxia/imunologia , Animais , Antialérgicos/isolamento & purificação , Abelhas , Líquido da Lavagem Broncoalveolar/imunologia , Movimento Celular/imunologia , Modelos Animais de Doenças , Peroxidase de Eosinófilo/efeitos dos fármacos , Peroxidase de Eosinófilo/metabolismo , Feminino , Flavonoides/isolamento & purificação , Imunoglobulina E/efeitos dos fármacos , Imunoglobulina E/imunologia , Imunoglobulina G/efeitos dos fármacos , Imunoglobulina G/imunologia , Leucócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Ratos , Ratos Wistar
17.
J R Soc Interface ; 4(17): 999-1030, 2007 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-17412675

RESUMO

The fields of tissue engineering and regenerative medicine aim at promoting the regeneration of tissues or replacing failing or malfunctioning organs, by means of combining a scaffold/support material, adequate cells and bioactive molecules. Different materials have been proposed to be used as both three-dimensional porous scaffolds and hydrogel matrices for distinct tissue engineering strategies. Among them, polymers of natural origin are one of the most attractive options, mainly due to their similarities with the extracellular matrix (ECM), chemical versatility as well as typically good biological performance. In this review, the most studied and promising and recently proposed naturally derived polymers that have been suggested for tissue engineering applications are described. Different classes of such type of polymers and their blends with synthetic polymers are analysed, with special focus on polysaccharides and proteins, the systems that are more inspired by the ECM. The adaptation of conventional methods or non-conventional processing techniques for processing scaffolds from natural origin based polymers is reviewed. The use of particles, membranes and injectable systems from such kind of materials is also overviewed, especially what concerns the present status of the research that should lead towards their final application. Finally, the biological performance of tissue engineering constructs based on natural-based polymers is discussed, using several examples for different clinically relevant applications.


Assuntos
Materiais Biocompatíveis , Medicina Regenerativa , Engenharia Tecidual
18.
J Nanosci Nanotechnol ; 7(3): 862-82, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17450849

RESUMO

With increasing interest in nanotechnology, development of nanofibers (n-fibers) by using the technique of electrospinning is gaining new momentum. Among important potential applications of n-fiber-based structures, scaffolds for tissue-engineering represent an advancing front. Nanoscaffolds (n-scaffolds) are closer to natural extracellular matrix (ECM) and its nanoscale fibrous structure. Although the technique of electrospinning is relatively old, various improvements have been made in the last decades to explore the spinning of submicron fibers from biodegradable polymers and to develop also multifunctional drug-releasing and bioactive scaffolds. Various factors can affect the properties of resulting nanostructures that can be classified into three main categories, namely: (1) Substrate related, (2) Apparatus related, and (3) Environment related factors. Developed n-scaffolds were tested for their cytocompatibility using different cell models and were seeded with cells for to develop tissue engineering constructs. Most importantly, studies have looked at the potential of using n-scaffolds for the development of blood vessels. There is a large area ahead for further applications and development of the field. For instance, multifunctional scaffolds that can be used as controlled delivery system do have a potential and have yet to be investigated for engineering of various tissues. So far, in vivo data on n-scaffolds are scarce, but in future reports are expected to emerge. With the convergence of the fields of nanotechnology, drug release and tissue engineering, new solutions could be found for the current limitations of tissue engineering scaffolds, which may enhance their functionality upon in vivo implantation. In this paper electrospinning process, factors affecting it, used polymers, developed n-scaffolds and their characterization are reviewed with focus on application in tissue engineering.


Assuntos
Materiais Biocompatíveis/química , Nanoestruturas/química , Engenharia Tecidual/métodos , Animais , Células Cultivadas , Sistemas de Liberação de Medicamentos , Eletroquímica/instrumentação , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Nanoestruturas/ultraestrutura , Nanotecnologia/instrumentação
19.
J Tissue Eng Regen Med ; 11(6): 1876-1887, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27035732

RESUMO

Wharton's jelly stem cells (WJSCs) are a potential source of transplantable stem cells in cartilage-regenerative strategies, due to their highly proliferative and multilineage differentiation capacity. We hypothesized that a non-direct co-culture system with human articular chondrocytes (hACs) could enhance the potential chondrogenic phenotype of hWJSCs during the expansion phase compared to those expanded in monoculture conditions. Primary hWJSCs were cultured in the bottom of a multiwell plate separated by a porous transwell membrane insert seeded with hACs. No statistically significant differences in hWJSCs duplication number were observed under either of the culture conditions during the expansion phase. hWJSCs under co-culture conditions show upregulations of collagen type I and II, COMP, TGFß1 and aggrecan, as well as of the main cartilage transcription factor, SOX9, when compared to those cultured in the absence of chondrocytes. Chondrogenic differentiation of hWJSCs, previously expanded in co-culture and monoculture conditions, was evaluated for each cellular passage using the micromass culture model. Cells expanded in co-culture showed higher accumulation of glycosaminoglycans (GAGs) compared to cells in monoculture, and immunohistochemistry for localization of collagen type I revealed a strong detection signal when hWJSCs were expanded under monoculture conditions. In contrast, type II collagen was detected when cells were expanded under co-culture conditions, where numerous round-shaped cell clusters were observed. Using a micromass differentiation model, hWJSCs, previously exposed to soluble factors secreted by hACs, were able to express higher levels of chondrogenic genes with deposition of cartilage extracellular matrix components, suggesting their use as an alternative cell source for treating degenerated cartilage. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Condrogênese , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/metabolismo , Cartilagem Articular/citologia , Condrócitos/citologia , Técnicas de Cocultura , Humanos , Células-Tronco Mesenquimais/citologia
20.
J Biomed Mater Res A ; 73(2): 234-43, 2005 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-15761811

RESUMO

We previously described the synthesis of starch-based microparticles that were shown to be bioactive (when combined with Bioactive Glass 45S5) and noncytotoxic. To further assess their potential for biomedical applications such as controlled release, three corticosteroids with a similar basic structure-dexamethasone (DEX), 16alpha-methylprednisonole (MP), and 16alpha-methylprednisolone acetate (MPA)-were used as models for the entrapment and release of bioactive agents. DEX, MP, and MPA were entrapped into starch-based microparticles at 10% wt/wt of the starch-based polymer and the loading efficiencies, as well as the release profiles, were evaluated. Differences were found for the loading efficiencies of the three corticosteroids, with DEX and MPA being the most successfully loaded (82 and 84%, respectively), followed by MP (51%). These differences might be explained based on the differential distribution of the molecules within the matrix of the microparticles. Furthermore, a differential burst release was observed in the first 24 h for all corticosteroids with DEX and MP being more pronounced (around 25%), whereas only 12% of MPA was released during the same time period. Whereas the water uptake profile can account for this first stage burst release, the subsequent slower release stage was mainly attributed to degradation of the microparticle network. Differences in the release profiles can be explained based on the structure of the molecule, because MPA, a more bulky and hydrophobic molecule, is released at a slower rate compared with DEX and MP. In this work, it is shown that these carriers were able to sustain a controlled release of the entrapped corticosteroids over 30 days, which confirms the potential of these systems to be used as carriers for the delivery of bioactive agents.


Assuntos
Dexametasona/farmacocinética , Metilprednisolona/análogos & derivados , Metilprednisolona/farmacocinética , Microesferas , Acetato de Metilprednisolona , Espectroscopia de Infravermelho com Transformada de Fourier , Amido , Fatores de Tempo , Água
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