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1.
Biomedicines ; 9(11)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34829786

RESUMO

The crosstalk among cancer cells (CCs) and stromal cells within the tumor microenvironment (TME) has a prominent role in cancer progression. The significance of endothelial cells (ECs) in this scenario relies on multiple vascular functions. By forming new blood vessels, ECs support tumor growth. In addition to their angiogenic properties, tumor-associated ECs (TECs) establish a unique vascular niche that actively modulates cancer development by shuttling a selected pattern of factors and metabolites to the CC. The profile of secreted metabolites is strictly dependent on the metabolic status of the cell, which is markedly perturbed in TECs. Recent evidence highlights the involvement of heme metabolism in the regulation of energy metabolism in TECs. The present study shows that interfering with endothelial heme metabolism by targeting the cell membrane heme exporter Feline Leukemia Virus subgroup C Receptor 1a (FLVCR1a) in TECs, resulted in enhanced fatty acid oxidation (FAO). Moreover, FAO-derived acetyl-CoA was partly consumed through ketogenesis, resulting in ketone bodies (KBs) accumulation in FLVCR1a-deficient TECs. Finally, the results from this study also demonstrate that TECs-derived KBs can be secreted in the extracellular environment, inducing a metabolic rewiring in the CC. Taken together, these data may contribute to finding new metabolic vulnerabilities for cancer therapy.

2.
Biomedicines ; 9(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34572271

RESUMO

The use of mesenchymal stem cells (MSCs) for regenerative purposes has become common in a large variety of diseases. In the dental and maxillofacial field, there are emerging clinical needs that could benefit from MSC-based therapeutic approaches. Even though MSCs can be isolated from different tissues, such as bone marrow, adipose tissue, etc., and are known for their multilineage differentiation, their different anatomical origin can affect the capability to differentiate into a specific tissue. For instance, MSCs isolated from the oral cavity might be more effective than adipose-derived stem cells (ASCs) for the treatment of dental defects. Indeed, in the oral cavity, there are different sources of MSCs that have been individually proposed as promising candidates for tissue engineering protocols. The therapeutic strategy based on MSCs can be direct, by using cells as components of the tissue to be regenerated, or indirect, aimed at delivering local growth factors, cytokines, and chemokines produced by the MSCs. Here, the authors outline the major sources of mesenchymal stem cells attainable from the oral cavity and discuss their possible usage in some of the most compelling therapeutic frontiers, such as periodontal disease and dental pulp regeneration.

3.
Cancers (Basel) ; 13(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34439343

RESUMO

Because of its high incidence and poor prognosis, colorectal cancer (CRC) represents an important health issue in several countries. As with other carcinomas, the so-called tumour microenvironment (TME) has been shown to play key roles in CRC progression and related therapeutical outcomes, even though a deeper understanding of the underlying molecular mechanisms is needed to devise new treatment strategies. For some years now, omics technologies and consolidated bioinformatics pipelines have allowed scientists to access large amounts of biologically relevant information, even when starting from small tissue samples; thus, in order to shed new light upon the role of the TME in CRC, we compared the gene expression profiles of 6 independent tumour tissues (all progressed towards metastatic disease) to the expression profile of the surrounding stromata. To do this, paraffin-embedded whole tissues were first microdissected to obtain samples enriched with tumour and stromal cells, respectively. Afterwards, RNA was extracted and analysed using a microarray-based approach. A thorough bioinformatics analysis was then carried out to identify transcripts differentially expressed between the two groups and possibly enriched functional terms. Overall, 193 genes were found to be significantly downregulated in tumours compared to the paired stromata. The functional analysis of the downregulated gene list revealed three principal macro areas of interest: the extracellular matrix, cell migration, and angiogenesis. Conversely, among the upregulated genes, the main alterations detected by the functional annotation were related to the ribosomal proteins (rProteins) of both the large (60S) and small (40S) subunits of the cytosolic ribosomes. Subsequent gene set enrichment analysis (GSEA) confirmed the massive overexpression of most cytosolic-but not mitochondrial-ribosome rProteins.

4.
Antioxidants (Basel) ; 10(8)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34439477

RESUMO

Proanthocyanidins (PACs) are a class of polyphenolic compounds that are attracting considerable interest in the nutraceutical field due to their potential health benefits. However, knowledge about the chemistry, biosynthesis, and distribution of PACs is limited. This review summarizes the main chemical characteristics and biosynthetic pathways and the main analytical methods aimed at their identification and quantification in raw plant matrices. Furthermore, meta-analytic approaches were used to identify the main plant sources in which PACs were contained and to investigate their potential effect on human health. In particular, a cluster analysis identified PACs in 35 different plant families and 60 different plant parts normally consumed in the human diet. On the other hand, a literature search, coupled with forest plot analyses, highlighted how PACs can be actively involved in both local and systemic effects. Finally, the potential mechanisms of action through which PACs may impact human health were investigated, focusing on their systemic hypoglycemic and lipid-lowering effects and their local anti-inflammatory actions on the intestinal epithelium. Overall, this review may be considered a complete report in which chemical, biosynthetic, ecological, and pharmacological aspects of PACs are discussed.

6.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800828

RESUMO

Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of Protium heptaphyllum gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS2 and GC-FID/MS identified 13 compounds mainly belonging to ursane, oleanane, and tirucallane groups. Studies on human hepatocytes have revealed how PHE is able to reduce cholesterol production and regulate the expression of proteins involved in its metabolism. (HMGCR, PCSK9, LDLR, FXR, IDOL, and PPAR). Moreover, measuring the inhibitory activity of PHE against HMGR, moderate inhibition was recorded. Finally, molecular docking studies identified acidic tetra- and pentacyclic triterpenoids as the main compounds responsible for this action. In conclusion, our study demonstrates how PHE may be a useful alternative to contrast hypercholesterolemia, highlighting its potential as a sustainable multitarget natural extract for the nutraceutical industry that is rapidly gaining acceptance as a source of health-promoting compounds.


Assuntos
Anticolesterolemiantes/farmacologia , Hidrogênio/química , Gomas Vegetais/química , Resinas Vegetais/química , Triterpenos/farmacologia , Anticolesterolemiantes/isolamento & purificação , Domínio Catalítico/efeitos dos fármacos , Colesterol/metabolismo , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais , Avaliação Pré-Clínica de Medicamentos , Ionização de Chama , Cromatografia Gasosa-Espectrometria de Massas , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lovastatina/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Conformação Proteica , Triterpenos/isolamento & purificação
7.
Biomedicines ; 9(3)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33800030

RESUMO

Mesenchymal stem cells (MSCs) can be harvested from different sites in the oral cavity, representing a reservoir of cells useful for regenerative purposes. As direct comparisons between at least two types of MSCs deriving from the same patient are surprisingly rare in scientific literature, we isolated and investigated the osteoinductive potential of dental pulp stem cells (DPSCs) and buccal fat pad stem cells (BFPSCs). MSCs were isolated from the third molar dental pulp and buccal fat pads of 12 patients. The number of viable cells was quantified through manual count. Proliferation and osteodifferentiation assays, flow cytometry analysis of cell phenotypes, and osteocalcin release in vitro were performed. The isolation of BFPSCs and DPSCs was successful in 7 out of 12 (58%) and 3 out of 12 (25%) of retrieved samples, respectively. The yield of cells expressing typical stem cell markers and the level of proliferation were higher in BFPSCs than in DPSCs. Both BFP-SCs and DPSCs differentiated into osteoblast-like cells and were able to release a mineralized matrix. The release of osteocalcin, albeit greater for BFPSCs, did not show any significant difference between BFPSCs and DPSCs. The yield of MSCs depends on their site of origin as well as on the protocol adopted for their isolation. Our data show that BFP is a valuable source for the derivation of MSCs that can be used for regenerative treatments.

8.
Pharmacol Res ; 168: 105581, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33781873

RESUMO

In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role of the deregulation of the heart-brain axis (HBA), a bidirectional flow of information, in leading to severe multiorgan disease syndrome (MODS) in patients with confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Noteworthy, HBA dysfunction may worsen the outcome of the COVID-19 patients. In this review, we discuss the critical role HBA plays in both promoting and limiting MODS in COVID-19. We also highlight the role of HBA as new target for novel therapeutic strategies in COVID-19 in order to open new translational frontiers of care. This is a translational perspective from the Italian Society of Cardiovascular Researches.


Assuntos
Encefalopatias/terapia , Encéfalo/efeitos dos fármacos , COVID-19/terapia , Cardiopatias/terapia , Coração/efeitos dos fármacos , Corticosteroides/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , Encéfalo/imunologia , Encéfalo/metabolismo , Encefalopatias/imunologia , Encefalopatias/metabolismo , COVID-19/imunologia , COVID-19/metabolismo , Cuidados Críticos/métodos , Estado Terminal/terapia , Suplementos Nutricionais , Alimento Funcional , Cardiopatias/imunologia , Cardiopatias/metabolismo , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Microvasos/efeitos dos fármacos , Microvasos/imunologia , Microvasos/metabolismo , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/terapia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-32809072

RESUMO

Calcium (Ca2+)-permeable channels are key players in different processes leading to blood vessel formation via sprouting angiogenesis, including endothelial cell (EC) proliferation and migration, as well as in controlling vascular features which are typical of the tumor vasculature.In this review we present an up-to-date and critical view on the role of Ca2+-permeable channels in tumor vascularization, emphasizing on the dual communication between growth factors (mainly VEGF) and Ca2+ signals. Due to the complexity of the tumor microenvironment (TME) as a source of multiple stimuli acting on the endothelium, we aim to discuss the close interaction between chemical and physical challenges (hypoxia, oxidative stress, mechanical stress) and endothelial Ca2+-permeable channels, focusing on transient receptor potential (TRP), store-operated Ca2+ channels (SOCs), and mechanosensitive Piezo channels. This approach will depict their crucial contribution in regulating key properties of tumor blood vessels, such as recruitment of endothelial progenitors cells (EPCs) in the early steps of tumor vascularization, abnormal EC migration and proliferation, and increased vascular permeability. Graphical abstract depicting the functional role of Ca2+-permeable TRP, SOCs and Piezo channels in the biological processes regulating tumor angiogenesis in presence of both chemical (oxidative stress and oxygen levels) and mechanical stimuli (ECM stiffness). SOCs store-operated Ca2+ channels, TRPA transient receptor potential ankyrin, TRPV transient receptor potential vanilloid, TRPC transient receptor potential canonical, TRPM transient receptor potential melastatin, TRPM transient receptor potential vanilloid, O2 oxygen, ECM extracellular matrix.

10.
J Cell Physiol ; 235(12): 10110-10115, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32567069

RESUMO

Here we present a new Fiji/ImageJ2 plugin called Multiparametric Morphometric Analysis of EUcaryotic cellS (MORPHEUS), designed for the automated evaluation of cell morphometry from images acquired by fluorescence microscopy. MORPHEUS works with sampling distributions to learn-in an unsupervised manner and by a nonparametric approach-how to recognize the cells suitable for subsequent analysis. Afterward, the algorithm performs the evaluation of the most relevant cell-shape descriptors over the full set of detected cells. Optionally, also the extraction of nucleus features and a double-scale analysis of orientation can be performed. The whole algorithm is implemented as a one-click procedure, thus minimizing the user's intervention. By reducing biases and errors of human origin, MORPHEUS is intended to be a useful tool to enhance reproducibility in the bioimage analysis.


Assuntos
Núcleo Celular/ultraestrutura , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência , Software , Algoritmos , Eucariotos/ultraestrutura , Humanos
11.
Front Physiol ; 11: 421, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431625

RESUMO

The vascular endothelium constitutes a semi-permeable barrier between blood and interstitial fluids. Since an augmented endothelial permeability is often associated to pathological states, understanding the molecular basis for its regulation is a crucial biomedical and clinical challenge. This review focuses on the processes controlling paracellular permeability that is the permeation of fluids between adjacent endothelial cells (ECs). Cytosolic calcium changes are often detected as early events preceding the alteration of the endothelial barrier (EB) function. For this reason, great interest has been devoted in the last decades to unveil the molecular mechanisms underlying calcium fluxes and their functional relationship with vessel permeability. Beyond the dicotomic classification between store-dependent and independent calcium entry at the plasma membrane level, the search for the molecular components of the related calcium-permeable channels revealed a difficult task for intrinsic and technical limitations. The contribution of redundant channel-forming proteins including members of TRP superfamily and Orai1, together with the very complex intracellular modulatory pathways, displays a huge variability among tissues and along the vascular tree. Moreover, calcium-independent events could significantly concur to the regulation of vascular permeability in an intricate and fascinating multifactorial framework.

12.
Int J Mol Sci ; 21(2)2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31947635

RESUMO

Hair loss is a disorder in which the hair falls out from skin areas such as the scalp and the body. Several studies suggest the use of herbal medicine to treat related disorders, including alopecia. Dermal microcirculation is essential for hair maintenance, and an insufficient blood supply can lead to hair follicles (HF) diseases. This work aims to provide an insight into the ethnohistorical records of some nutritional compounds containing flavonoids for their potential beneficial features in repairing or recovering from hair follicle disruption. We started from a query for "alopecia" OR "hair loss" AND "Panax ginseng C.A. Mey." (or other six botanicals) terms included in Pubmed and Web of Sciences articles. The activities of seven common botanicals introduced with diet (Panax ginseng C.A. Mey., Malus pumila Mill cultivar Annurca, Coffea arabica, Allium sativum L., Camellia sinensis (L.) Kuntze, Rosmarinum officinalis L., Capsicum annum L.) are discussed, which are believed to reduce the rate of hair loss or stimulate new hair growth. In this review, we pay our attention on the molecular mechanisms underlying the bioactivity of the aforementioned nutritional compounds in vivo, ex vivo and in vitro studies. There is a need for systematic evaluation of the most commonly used plants to confirm their anti-hair loss power, identify possible mechanisms of action, and recommend their best adoption.


Assuntos
Flavonoides/farmacologia , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Plantas Comestíveis/química , Plantas Medicinais/química , Animais , Flavonoides/química , Flavonoides/metabolismo , Humanos , Redes e Vias Metabólicas , Estrutura Molecular , Extratos Vegetais/química , Plantas Comestíveis/metabolismo , Plantas Medicinais/metabolismo
13.
Int J Mol Sci ; 20(24)2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31817884

RESUMO

Endothelial cells present in tumors show different origin, phenotype, and genotype with respect to the normal counterpart. Various mechanisms of intra-tumor vasculogenesis sustain the complexity of tumor vasculature, which can be further modified by signals deriving from the tumor microenvironment. As a result, resistance to anti-VEGF therapy and activation of compensatory pathways remain a challenge in the treatment of cancer patients, revealing the need to explore alternative strategies to the classical anti-angiogenic drugs. In this review, we will describe some alternative strategies to inhibit tumor vascularization, including targeting of antigens and signaling pathways overexpressed by tumor endothelial cells, the development of endothelial vaccinations, and the use of extracellular vesicles. In addition, anti-angiogenic drugs with normalizing effects on tumor vessels will be discussed. Finally, we will present the concept of endothelial demesenchymalization as an alternative approach to restore normal endothelial cell phenotype.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias/tratamento farmacológico , Neovascularização Patológica/prevenção & controle , Microambiente Tumoral/efeitos dos fármacos , Animais , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/patologia
14.
Front Physiol ; 10: 1291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681005

RESUMO

The synergistic crosstalk between osteodifferentiating stem cells and endothelial cells (ECs) gained the deserved consideration, shedding light on the role of angiogenesis for bone formation and healing. A deep understanding of the molecular basis underlying the mutual influence of mesenchymal stem cells (MSCs) and ECs in the osteogenic process may help improve greatly bone regeneration. Here, the authors demonstrated that osteodifferentiating MSCs co-cultured with ECs promote angiogenesis and ECs recruitment. Moreover, through the use of 3D co-culture systems, we showed that ECs are in turn able to further stimulate the osteodifferentiation of MSCs, thus enhancing bone production. These findings highlighted the existence of a virtuous loop between MSCs and ECs that is central to the osteogenic process. Unraveling the molecular mechanisms governing the functional interaction MSCs and ECs holds great potential in the field of regenerative medicine.

15.
Cancers (Basel) ; 11(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288452

RESUMO

Background: Transient receptor potential (TRP) channels control multiple processes involved in cancer progression by modulating cell proliferation, survival, invasion and intravasation, as well as, endothelial cell (EC) biology and tumor angiogenesis. Nonetheless, a complete TRP expression signature in tumor vessels, including in prostate cancer (PCa), is still lacking. Methods: In the present study, we profiled by qPCR the expression of all TRP channels in human prostate tumor-derived ECs (TECs) in comparison with TECs from breast and renal tumors. We further functionally characterized the role of the 'prostate-associated' channels in proliferation, sprout formation and elongation, directed motility guiding, as well as in vitro and in vivo morphogenesis and angiogenesis. Results: We identified three 'prostate-associated' genes whose expression is upregulated in prostate TECs: TRPV2 as a positive modulator of TEC proliferation, TRPC3 as an endothelial PCa cell attraction factor and TRPA1 as a critical TEC angiogenic factor in vitro and in vivo. Conclusions: We provide here the full TRP signature of PCa vascularization among which three play a profound effect on EC biology. These results contribute to explain the aggressive phenotype previously observed in PTEC and provide new putative therapeutic targets.

16.
Cancers (Basel) ; 11(6)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31159426

RESUMO

Tumor microenvironment is particularly enriched with extracellular ATP (eATP), but conflicting evidence has been provided on its functional effects on tumor growth and vascular remodeling. We have previously shown that high eATP concentrations exert a strong anti-migratory, antiangiogenic and normalizing activity on human tumor-derived endothelial cells (TECs). Since both metabotropic and ionotropic purinergic receptors trigger cytosolic calcium increase ([Ca2+]c), the present work investigated the properties of [Ca2+]c events elicited by high eATP in TECs and their role in anti-migratory activity. In particular, the quantitative and kinetic properties of purinergic-induced Ca2+ release from intracellular stores and Ca2+ entry from extracellular medium were investigated. The main conclusions are: (1) stimulation of TECs with high eATP triggers [Ca2+]c signals which include Ca2+ mobilization from intracellular stores (mainly ER) and Ca2+ entry through the plasma membrane; (2) the long-lasting Ca2+ influx phase requires both store-operated Ca2+ entry (SOCE) and non-SOCE components; (3) SOCE is not significantly involved in the antimigratory effect of high ATP stimulation; (4) ER is the main source for intracellular Ca2+ release by eATP: it is required for the constitutive migratory potential of TECs but is not the only determinant for the inhibitory effect of high eATP; (5) a complex interplay occurs among ER, mitochondria and lysosomes upon purinergic stimulation; (6) high eUTP is unable to inhibit TEC migration and evokes [Ca2+]c signals very similar to those described for eATP. The potential role played by store-independent Ca2+ entry and Ca2+-independent events in the regulation of TEC migration by high purinergic stimula deserves future investigation.

17.
J Ethnopharmacol ; 238: 111844, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30940568

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Several traditional medicinal herbs are widely used for dermatologic and cosmetic preparations. The beneficial skin repair activity is detected in various phases of wound-healing process, such as cell-cell, cell-matrix interactions or collagen synthesis. AIM OF THE STUDY: The study assessed the effects of Opuntia ficus-indica (L.) Mill. (Opuntia) and Milk Thistle (MT) (Silybum marianum (L.) Gaerth) on adult keratinocytes (HaCaT) functioning under basal condition or in the presence of mechanical damage (wounded cells). MATERIALS AND METHODS: The role of the natural compounds was tested on HaCaT grown in mono-culture and tri-culture configurations. In tri-cultures models, HaCaT were treated with the conditioned media (CM) obtained by Human Normal Dermal Fibroblast (NHDF) and Human Dermal Microvascular Endothelial cells (HMVEC) co-cultures. Specifically, were tested cell viability, oxidative stress mechanisms (cytokines release and lipid peroxidation) and cellular remodelling (growth factors release or metalloproteinase modulation). Moreover, the migratory potential of HaCaT was analysed by the use of wound healing in vitro assay. RESULTS: Opuntia and MT differently modified the metabolism (EGF, MMP-9), and the migratory properties of HaCaT both under physiological conditions or upon mechanical damage (wounded cells). Moreover, both compounds modulated HaCaT response to oxidative stress. The response to the natural compounds were modified, and in some cases potentiated, in tri-culture configuration systems. CONCLUSIONS: The data demonstrated that in vitro tri-culture approach is suitable to characterize the role of natural compounds on the complex communication between dermal-epidermal cellular components and microvascular endothelium. Specifically, Opuntia and MT are good alternatives to synthetic compounds in skin repair promotion.


Assuntos
Antioxidantes/farmacologia , Células Endoteliais/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Flavonoides/farmacologia , Queratinócitos/efeitos dos fármacos , Cardo-Mariano , Opuntia , Técnicas de Cultura de Células , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Meios de Cultivo Condicionados , Dieta , Células Endoteliais/fisiologia , Fibroblastos/fisiologia , Humanos , Queratinócitos/fisiologia , Cicatrização/efeitos dos fármacos
18.
Nanomedicine (Lond) ; 14(5): 575-594, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30810075

RESUMO

AIM: To clarify the mechanisms of interaction between SiO2 nanoparticles (NPs) and the plasma membrane of GT1-7 neuroendocrine cells, with focus on the activation of calcium-permeable channels, responsible for the long lasting calcium influx and modulation of the electrical activity in these cells. MATERIALS & METHODS: Nontoxic doses of SiO2 NPs were administered to the cells. Calcium imaging and patch clamp techniques were combined with a pharmacological approach. RESULTS: TRPV4, Cx and Panx-like channels are the major components of the NP-induced inward currents. Preincubation with the antioxidant N-acetyl-L-cysteine strongly reduced the [Ca2+]i increase. CONCLUSION: These findings suggest that SiO2 NPs directly activate a complex set of calcium-permeable channels, possibly by catalyzing free radical production.


Assuntos
Nanopartículas/química , Dióxido de Silício/química , Animais , Cálcio/metabolismo , Linhagem Celular , Membrana Celular/metabolismo , Eletrofisiologia , Peroxidação de Lipídeos/fisiologia , Camundongos , Microscopia Eletrônica de Transmissão , Neurônios/metabolismo , Canais de Cátion TRPV/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-30652649

RESUMO

BACKGROUND: Purinergic signalling is involved in several physiological and pathophysiological processes. P2X7 Receptor (P2X7R) is a calcium-permeable ion channel that is gaining interest as a potential therapeutic target for the treatment of different diseases including inflammation, pain, psychiatric disorders and cancer. P2X7R is ubiquitously expressed and sensitive to high ATP levels, usually found in tumor microenvironment. P2X7R regulates several cell functions, from migration to cell death, but its selective contribution to tumor progression remains controversial. OBJECTIVE: Current review was conducted to check involvement of P2X7R use in cancer treatment. METHODS: We review the most recent patents focused on the use of P2X7R in the treatment of cancer. RESULTS: P2X7R is an intriguing purinergic receptor that plays different roles in tumor progression. CONCLUSION: Powerful strategies able to selectively interfere with its expression and function should reveal helpful in the development of new anti-cancer therapies.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Receptores Purinérgicos P2X7/biossíntese , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Humanos , Neoplasias/metabolismo , Patentes como Assunto , Antagonistas do Receptor Purinérgico P2X/farmacologia , Microambiente Tumoral/fisiologia
20.
J Cell Physiol ; 234(5): 7320-7329, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30417926

RESUMO

Current treatments for hair follicle (HF) disruption are based on 5-α reductase inhibitors and prostaglandin modulators. Botanicals and nutraceutical compounds interfere with hair loss or stimulate its partial regrowth. Here, we used in vitro cocultures to investigate the activity of Serenoa repens ( SR) and N-acetyl glucosamine + milk proteins (NAG/Lac) on the paracrine interactions between human microvascular endothelial cells (HMVEC) and HF dermal papilla cells (FDPC). Both SR and NAG/Lac-induced endothelial tubulogenesis were enhanced by FDPC. SR promoted proliferation of both the cell types, while NAG/Lac was effective on endothelium. Vascular endothelial growth factor production, enhanced by SR, was further augmented by FDPC. In FDPC 5-α reductase-II and ß-catenin expressions were modified by SR and less by NAG/Lac, with no additional effect by HMVEC. SR and NAG/Lac prevented lipid peroxidation, whereas NAG/Lac was effective on interleukin 1ß production. Finally, SR and NAG/Lac differentially affected HMVEC permeability and tight junction proteins content. These data provide a mechanistic background for the potential use of these compounds as promoters of HF vascularization.


Assuntos
Acetilglucosamina/farmacologia , Indutores da Angiogênese/farmacologia , Células Endoteliais/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Proteínas do Leite/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Comunicação Parácrina/efeitos dos fármacos , Extratos Vegetais/farmacologia , Serenoa , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Células Endoteliais/metabolismo , Folículo Piloso/citologia , Folículo Piloso/metabolismo , Humanos , Interleucina-1beta/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Permeabilidade , Extratos Vegetais/isolamento & purificação , Serenoa/química , Transdução de Sinais , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
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