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1.
Biochem Biophys Res Commun ; 733: 150726, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39317114

RESUMO

Type I collagen is among the major extracellular proteins that play a significant role in the maintenance of the cornea's structural integrity and is essential in cell adhesion, differentiation, growth, and integrity. Here, we investigated the effect of 300 mT Static Magnetic Field (300 mT SMF) on the structure and molecular properties of acid-solubilized collagens (ASC) isolated from the rat tail tendon. The SMF effects at molecular and atomic levels were investigated by various biophysical approaches like Circular Dichroism Spectropolarimetery (CD), Fourier Transform Infrared Spectroscopy (FTIR), Zetasizer light Scattering, and Rheological assay. Exposure of isolated type I collagen to 300 mT SMF retained its triple helix. The elasticity of collagen molecules and the keratoconus (KCN) cornea treated with SMF decreased significantly after 5 min and slightly after 10, 15, and 20 min of treatments. The exposure to 300 mT SMF shifted the Amid I bond random coil to antiparallel wave number from 1647 to 1631 cm-1. The pH of the 300 mT SMF treated collagen solution increased by about 25 %. The treatment of the KCN corneas with 300 mT SMF decreased their elasticity significantly. The promising results of the effects of 300 mT SMF on the collagen molecules and KCN cornea propose a novel biophysical approach capable of manipulating the collagen's elasticity, surface charges, electrostatic interactions, cross binding, network formation and fine structure. Therefore, SMF treatment may be considered as a novel non-invasive, direct, non-chemical and fast therapeutic and manipulative means to treat KCN cornea where the deviated physico-chemical status of collagen molecules cause deformation.

2.
Int J Mol Sci ; 25(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38892363

RESUMO

Autophagy plays a key role in removing protein aggregates and damaged organelles. In addition to its conventional degradative functions, autophagy machinery contributes to the release of cytosolic proteins through an unconventional secretion pathway. In this research, we analyzed autophagy-induced extracellular vesicles (EVs) in HT1080-derived human fibrosarcoma 2FTGH cells using transmission electron microscopy and atomic force microscopy (AFM). We preliminary observed that autophagy induces the formation of a subset of large heterogeneous intracellular vesicular structures. Moreover, AFM showed that autophagy triggering led to a more visible smooth cell surface with a reduced amount of plasma membrane protrusions. Next, we characterized EVs secreted by cells following autophagy induction, demonstrating that cells release both plasma membrane-derived microvesicles and exosomes. A self-forming iodixanol gradient was performed for cell subfractionation. Western blot analysis showed that endogenous LC3-II co-fractionated with CD63 and CD81. Then, we analyzed whether raft components are enriched within EV cargoes following autophagy triggering. We observed that the raft marker GD3 and ER marker ERLIN1 co-fractionated with LC3-II; dual staining by immunogold electron microscopy and coimmunoprecipitation revealed GD3-LC3-II association, indicating that autophagy promotes enrichment of raft components within EVs. Introducing a new brick in the crosstalk between autophagy and the endolysosomal system may have important implications for the knowledge of pathogenic mechanisms, suggesting alternative raft target therapies in diseases in which the generation of EV is active.


Assuntos
Autofagia , Vesículas Extracelulares , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/ultraestrutura , Linhagem Celular Tumoral , Microdomínios da Membrana/metabolismo , Exossomos/metabolismo , Exossomos/ultraestrutura , Tetraspanina 30/metabolismo , Fibrossarcoma/metabolismo , Fibrossarcoma/patologia , Proteínas Associadas aos Microtúbulos/metabolismo
3.
Phytopathology ; 114(7): 1466-1479, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38700944

RESUMO

Xylella fastidiosa (Xf) is a quarantine plant pathogen capable of colonizing the xylem of a wide range of hosts. Currently, there is no cure able to eliminate the pathogen from a diseased plant, but several integrated strategies have been implemented for containing the spread of Xf. Nanotechnology represents an innovative strategy based on the possibility of maximizing the potential antibacterial activity by increasing the surface-to-volume ratio of nanoscale formulations. Nanoparticles based on chitosan and/or fosetyl-Al have shown different in vitro antibacterial efficacy against Xf subsp. fastidiosa (Xff) and pauca (Xfp). This work demonstrated the uptake of chitosan-coated fosetyl-Al nanocrystals (CH-nanoFos) by roots and their localization in the stems and leaves of Olea europaea plants. Additionally, the antibacterial activity of fosetyl-Al, nano-fosetyl, nano-chitosan, and CH-nanoFos was tested on Nicotiana tabacum cultivar SR1 (Petite Havana) inoculated with Xff, Xfp, or Xf subsp. multiplex (Xfm). The bacterial load was evaluated with qPCR, and the results showed that CH-nanoFos was the only treatment able to reduce the colonization of Xff, Xfm, and Xfp in tobacco plants. Additionally, the area under the disease progress curve, used to assess symptom development in tobacco plants inoculated with Xff, Xfm, and Xfp and treated with CH-nanoFos, showed a reduction in symptom development. Furthermore, the twitching assay and bacterial growth under microfluidic conditions confirmed the antibacterial activity of CH-nanoFos.


Assuntos
Quitosana , Nanopartículas , Nicotiana , Doenças das Plantas , Xylella , Xylella/fisiologia , Xylella/efeitos dos fármacos , Quitosana/farmacologia , Quitosana/química , Nicotiana/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Folhas de Planta/microbiologia , Raízes de Plantas/microbiologia , Olea/microbiologia
4.
Nanoscale ; 16(16): 8132-8142, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38568015

RESUMO

Tip-enhanced Raman spectroscopy (TERS) is an advanced technique to perform local chemical analysis of the surface of a sample through the improvement of the sensitivity and the spatial resolution of Raman spectroscopy by plasmonic enhancement of the electromagnetic signal in correspondence with the nanometer-sized tip of an atomic force microscope (AFM). In this work, TERS is demonstrated to represent an innovative and powerful approach for studying extracellular vesicles, in particular bovine milk-derived extracellular vesicles (mEVs), which are nanostructures with considerable potential in drug delivery and therapeutic applications. Raman spectroscopy has been used to analyze mEVs at the micrometric and sub-micrometric scales to obtain a detailed Raman spectrum in order to identify the 'signature' of mEVs in terms of their characteristic molecular vibrations and, therefore, their chemical compositions. With the ability to improve lateral resolution, TERS has been used to study individual mEVs, demonstrating the possibility of investigating a single mEV selected on the surface of the sample and, moreover, analyzing specific locations on the selected mEV with nanometer lateral resolution. TERS potentially allows one to reveal local differences in the composition of mEVs providing new insights into their structure. Also, thanks to the intrinsic properties of TERS to acquire the signal from only the first few nanometers of the surface, chemical investigation of the lipid membrane in correspondence with the various locations of the selected mEV could be performed by analyzing the peaks of the Raman shift in the relevant range of the spectrum (2800-3000 cm-1). Despite being limited to mEVs, this work demonstrates the potential of TERS in the analysis of extracellular vesicles.


Assuntos
Vesículas Extracelulares , Microscopia de Força Atômica , Leite , Análise Espectral Raman , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Animais , Bovinos , Leite/química
5.
Cell Commun Signal ; 22(1): 193, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539237

RESUMO

BACKGROUND: Macrophages release not only cytokines but also extracellular vesicles (EVs). which are small membrane-derived nanovesicles with virus-like properties transferring cellular material between cells. Until now, the consequences of macrophage plasticity on the release and the composition of EVs have been poorly explored. In this study, we determined the impact of high-glucose (HG) concentrations on macrophage metabolism, and characterized their derived-EV subpopulations. Finally, we determined whether HG-treated macrophage-derived EVs participate in immune responses and in metabolic alterations of skeletal muscle cells. METHODS: THP1-macrophages were treated with 15mM (MG15) or 30mM (MG30) glucose. Then, M1/M2 canonical markers, pro- and anti-inflammatory cytokines, activities of proteins involved in glycolysis or oxidative phosphorylation were evaluated. Macrophage-derived EVs were characterized by TEM, NTA, MRSP, and 1H-Nuclear magnetic resonance spectroscopy for lipid composition. Macrophages or C2C12 muscle cells were used as recipients of MG15 and MG30-derived EVs. The lipid profiles of recipient cells were determined, as well as proteins and mRNA levels of relevant genes for macrophage polarization or muscle metabolism. RESULTS: Untreated macrophages released small and large EVs (sEVs, lEVs) with different lipid distributions. Proportionally to the glucose concentration, glycolysis was induced in macrophages, associated to mitochondrial dysfunction, triacylglycerol and cholesterol accumulation. In addition, MG15 and MG30 macrophages had increased level of CD86 and increase release of pro-inflammatory cytokines. HG also affected macrophage sphingolipid and phospholipid compositions. The differences in the lipid profiles between sEVs and lEVs were abolished and reflected the lipid alterations in MG15 and MG30 macrophages. Interestingly, MG15 and MG30 macrophages EVs induced the expression of CD163, Il-10 and increased the contents of triacylglycerol and cholesterol in recipient macrophages. MG15 lEVs and sEVs induced insulin-induced AKT hyper-phosphorylation and accumulation of triacylglycerol in myotubes, a state observed in pre-diabetes. Conversely, MG30 lEVs and sEVs induced insulin-resistance in myotubes. CONCLUSIONS: As inflammation involves first M1 macrophages, then the activation of M2 macrophages to resolve inflammation, this study demonstrates that the dialog between macrophages through the EV route is an intrinsic part of the inflammatory response. In a hyperglycemic context, EV macrophages could participate in the development of muscle insulin-resistance and chronic inflammation.


Assuntos
Vesículas Extracelulares , Insulinas , Humanos , Macrófagos/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Vesículas Extracelulares/metabolismo , Lipídeos , Homeostase , Triglicerídeos/metabolismo , Colesterol/metabolismo , Insulinas/metabolismo
6.
World J Stem Cells ; 15(8): 821-841, 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37700819

RESUMO

BACKGROUND: Cardiovascular diseases particularly myocardial infarction (MI) are the leading cause of mortality and morbidity around the globe. As cardiac tissue possesses very limited regeneration potential, therefore use of a potent small molecule, inhibitor Wnt production-4 (IWP-4) for stem cell differentiation into cardiomyocytes could be a promising approach for cardiac regeneration. Wnt pathway inhibitors may help stem cells in their fate determination towards cardiomyogenic lineage and provide better homing and survival of cells in vivo. Mesenchymal stem cells (MSCs) derived from the human umbilical cord have the potential to regenerate cardiac tissue, as they are easy to isolate and possess multilineage differentiation capability. IWP-4 may promote the differentiation of MSCs into the cardiac lineage. AIM: To evaluate the cardiac differentiation ability of IWP-4 and its subsequent in vivo effects. METHODS: Umbilical cord tissue of human origin was utilized to isolate the MSCs which were characterized by their morphology, immunophenotyping of surface markers specific to MSCs, as well as by tri-lineage differentiation capability. Cytotoxicity analysis was performed to identify the optimal concentration of IWP-4. MSCs were treated with 5 µM IWP-4 at two different time intervals. Differentiation of MSCs into cardiomyocytes was evaluated at DNA and protein levels. The MI rat model was developed. IWP-4 treated as well as untreated MSCs were implanted in the MI model, then the cardiac function was analyzed via echocardiography. MSCs were labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) dye for tracking, while the regeneration of infarcted myocardium was examined by histology and immunohistochemistry. RESULTS: MSCs were isolated and characterized. Cytotoxicity analysis showed that IWP-4 was non-cytotoxic at 5 µM concentration. Cardiac specific gene and protein expression analyses exhibited more remarkable results in fourteen days treated group that was eventually selected for in vivo transplantation. Cardiac function was restored in the IWP-4 treated group in comparison to the MI group. Immunohistochemical analysis confirmed the homing of pre-differentiated MSCs that were labeled with DiI cell labeling dye. Histological analysis confirmed the significant reduction in fibrotic area, and improved left ventricular wall thickness in IWP-4 treated MSC group. CONCLUSION: Treatment of MSCs with IWP-4 inhibits Wnt pathway and promotes cardiac differentiation. These pre-conditioned MSCs transplanted in vivo improved cardiac function by cell homing, survival, and differentiation at the infarcted region, increased left ventricular wall thickness, and reduced infarct size.

7.
Sci Total Environ ; 864: 161032, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36549536

RESUMO

In this study, we investigated the presence, abundance, and chemical nature of microplastics (MPs) in the freshwater fish gastrointestinal tract in the South of Italy, and evaluated the possible correlation between MPs and environmental pollutants. Fifty specimens belonging to five species (Scardinius erythrophthalmus, Barbus barbus, Rutilus rubilio, Leuciscus cephalus, Salmo trutta), from twenty sites were collected. MPs chemical feature was identified by means of Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) and Raman microscopy. MPs were represented by 34.86 % fragments, film, and foam (all together MPs) and 65.14 % by fibers (MFs). The mean number of MPs/MFs per fish ranged from 6.25 ± 4.35 in R. rubilio and 2.26 ± 1.94 in B. barbus. The highest number of MPs/MFs per g of GIT was found in R. rubilio (9.07 ± 9.66), and the lowest in S. erythrophthalmus (0.75 ± 0.53). The highest number of MPs/MFs per fish species was found in L. cephalus (16), and the lowest in S. erythrophthalmus (4). Black predominated in every type of plastic debris identified, followed by blue and white, respectively for MFs and MPs. Polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), and polypropylene (PP), were the main plastic polymers found. At fish sampling sites, comparing concentrations in soils of potentially toxic elements and persistent organic pollutants with the number of MPs/MFs in fish, a significant correlation was noted with polychlorinated biphenyls (PCBs) and, in particular, with PCB 105, PCB 118, PCB 156, PCB 157, and PCB 167. A strong correlation was also observed with all types of polycyclic aromatic hydrocarbon (PAHs) particularly with benzo(ghi)perylene, dibenz(a,h)anthracene, benzo(b)fluoranthene, benz(a)anthracene, benzo(a)pyrene, and pyrene. The results of this study would be useful to draft management and action plans, promote intervention plans aiming at removing threats to species and habitats, and address ways of renaturalization.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Animais , Microplásticos , Plásticos/química , Água Doce , Peixes , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos
8.
J Pers Med ; 12(11)2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36579532

RESUMO

Hepatic fibrosis (HF) is a major cause of liver-related disorders and together with cancer-associated fibroblasts can favor liver cancer development by modulating the tumor microenvironment. Advanced HF, characterized by an excess of extracellular matrix (ECM), is mediated by TGF- ß1, that activates hepatic stellate cells (HSCs) and fibroblasts. A TGF-ß1 receptor inhibitor, LY2157299 or Galunisertib (GLY), has shown promising results against chronic liver progression in animal models, and we show that it can be further improved by enhancing GLYs bioavailability through encapsulation in polymeric polygalacturonic-polyacrylic acid nanomicelles (GLY-NMs). GLY-NMs reduced HF in an in vivo rat model of liver fibrosis induced by intraperitoneal injection of CCl4 as shown by the morphological, biochemical, and molecular biology parameters of normal and fibrotic livers. Moreover, GLY-NM was able to induce recovery from HF better than free GLY. Indeed, the encapsulated drug reduces collagen deposition, hepatic stellate cells (HSCs) activation, prevents fatty degeneration and restores the correct lobular architecture of the liver as well as normalizes the serum parameters and expression of the genes involved in the onset of HF. In summary, GLY-NM improved the pharmacological activity of the free TGF- ß1 inhibitor in the in vivo HF treatment and thus is a candidate as a novel therapeutic strategy.

9.
Nat Nanotechnol ; 17(10): 1111-1119, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36097045

RESUMO

The distinctive properties of single-walled carbon nanotubes (SWCNTs) have inspired the development of many novel applications in the field of cell nanobiotechnology. However, studies thus far have not explored the effect of SWCNT functionalization on transport across the cell walls of prokaryotes. We explore the uptake of SWCNTs in Gram-negative cyanobacteria and demonstrate a passive length-dependent and selective internalization of SWCNTs decorated with positively charged biomolecules. We show that lysozyme-coated SWCNTs spontaneously penetrate the cell walls of a unicellular strain and a multicellular strain. A custom-built spinning-disc confocal microscope was used to image the distinct near-infrared SWCNT fluorescence within the autofluorescent cells, revealing a highly inhomogeneous distribution of SWCNTs. Real-time near-infrared monitoring of cell growth and division reveal that the SWCNTs are inherited by daughter cells. Moreover, these nanobionic living cells retained photosynthetic activity and showed an improved photo-exoelectrogenicity when incorporated into bioelectrochemical devices.


Assuntos
Cianobactérias , Nanotubos de Carbono , Diagnóstico por Imagem , Fluorescência , Muramidase , Nanotubos de Carbono/química
10.
Environ Toxicol Pharmacol ; 95: 103956, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35963553

RESUMO

Nanoparticles have found use in a wide range of applications, mainly as carriers of active biomolecules. It is thus necessary to assess their toxicity for human health, as well as for the environment, on which there is still a gap of knowledge. In this work, sea urchin Paracentrotus lividus, a widely used model for embryotoxicity and spermiotoxicity, has been used to assess potential detrimental effects of amino-functionalized mesoporous silica nanoparticles (NH2-MSiNPs) on embryonic development. Specifically, gametes quality, embryogenesis morphological and timing alterations, and cellular stress markers, such as mitochondrial functionality, were assessed in presence of different concentrations of NH2-MSiNPs in filtered seawater (FSW). Furthermore, dorsal-ventral axis development and skeletogenesis were characterized by microscopy imaging and gene expression analysis. NH2-MSiNPs determined a strong reduction in the egg fertilization rate. Consequently, the presence of NH2-MSiNPs resulted detrimental in P. lividus embryonic development, with severe morphological alterations correlated with an increased embryos mortality. Finally, NH2-MSiNPs treatment was responsible for other toxic effects, such as reduced mitochondrial function and skeletogenesis alterations, according to the reduced mineralization sites in the endoskeleton formation and the related genes altered expression. Taken together, these results suggest the potential toxic effects of NH2-MSiNPs on the marine ecosystem, with consequences for the development and reproduction of its organisms. Despite their promising potential as carriers of biomolecules, it is pivotal to consider that their uncontrolled use may result harmful to the environment and, consequently, to living organisms.


Assuntos
Nanopartículas , Paracentrotus , Animais , Ecossistema , Embrião não Mamífero , Desenvolvimento Embrionário , Humanos , Nanopartículas/toxicidade , Paracentrotus/genética , Dióxido de Silício/toxicidade
11.
J Tissue Eng Regen Med ; 16(7): 665-679, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35470546

RESUMO

The moderate static magnetic fields (SMFs) have been used here as a non-invasive tool to study their manipulative effects on the olfactory ensheathing cells (OECs) activity, growth, morphology, and migration in culture. The OECs are involved in the regeneration of primary olfactory sensory neurons and migration into the central nervous system to repair axons damaged by infection, injury, etc., that play a pivotal role in complementary regenerative medicine. Here, OECs were isolated from the olfactory bulb and cultured to confluence. An in vitro wound healing model was formed and exposed to either parallel (PaSMF) or perpendicular (PeSMF) SMF at intensities of 30, 50, and 70 mT, and cells' morphology, podia formation, proliferation, and migration were studied by time-lapse recording. The SMFs were not cytotoxic at the intensity and exposure time applied here. The exposure of cells to 70 mT PaSMF and PeSMF increased the formation of lamellipodia and filopodia, cell migration speed, and direction of the scratch forefront cells, significantly. Treatment of cells with 70 mT PaSMF and PeSMF increased cell divisions, while 30 mT PaSMF decreased it. SMF effects on OECs division, motility, migratory direction, and velocity indicate its effect on various aspects of cell physiology and signaling at atomic and molecular levels, and have a role in tissue regeneration that involves microtubules and actin filaments formation and rearrangements. Thus, the exposure of OECs with moderate SMF might be considered a promising noninvasive approach to remotely manipulate normal and stem cell activities for therapeutic regenerative purposes in various tissues including the central nervous system.


Assuntos
Axônios , Bulbo Olfatório , Movimento Celular , Células Cultivadas , Campos Magnéticos , Regeneração Nervosa/fisiologia , Pseudópodes
13.
Nanomaterials (Basel) ; 11(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34443862

RESUMO

Technological innovation, environmental sustainability, health, and wellness are the trajectories explored by current research to identify new strategies for a general improvement of human quality of life [...].

14.
Antioxidants (Basel) ; 10(8)2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34439537

RESUMO

Long-term high-fat diet (HFD) consumption can cause weight gain and obesity, two conditions often associated with hepatic non-alcoholic fatty liver and oxidative stress. Oleoylethanolamide (OEA), a lipid compound produced by the intestine from oleic acid, has been associated with different beneficial effects in diet-induced obesity and hepatic steatosis. However, the role of OEA on hepatic oxidative stress has not been fully elucidated. In this study, we used a model of diet-induced obesity to study the possible antioxidant effect of OEA in the liver. In this model rats with free access to an HFD for 77 days developed obesity, steatosis, and hepatic oxidative stress, as compared to rats consuming a low-fat diet for the same period. Several parameters associated with oxidative stress were then measured after two weeks of OEA administration to diet-induced obese rats. We showed that OEA reduced, compared to HFD-fed rats, obesity, steatosis, and the plasma level of triacylglycerols and transaminases. Moreover, OEA decreased the amount of malondialdehyde and carbonylated proteins and restored the activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, which decreased in the liver of HFD-fed rats. OEA had also an improving effect on parameters linked to endoplasmic reticulum stress, thus demonstrating a role in the homeostatic control of protein folding. Finally, we reported that OEA differently regulated the expression of two transcription factors involved in the control of lipid metabolism and antioxidant genes, namely nuclear factor erythroid-derived 2-related factor 1 (Nrf1) and Nrf2, thus suggesting, for the first time, new targets of the protective effect of OEA in the liver.

15.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066354

RESUMO

All nervous system pathologies (e.g., neurodegenerative/demyelinating diseases and brain tumours) develop neuroinflammation, a beneficial process during pathological events, aimed at removing damaged cells, toxic agents, and/or pathogens. Unfortunately, excessive inflammation frequently occurs during nervous system disorders, becoming a detrimental event capable of enhancing neurons and myelinating glial cell impairment, rather than improving their survival and activity. Consequently, targeting the neuroinflammation could be relevant for reducing brain injury and rescuing neuronal and glial cell functions. Several studies have highlighted the role of acetylcholine and its receptors in the regulation of central and peripheral inflammation. In particular, α7 nicotinic receptor has been described as one of the main regulators of the "brain cholinergic anti-inflammatory pathway". Its expression in astrocytes and microglial cells and the ability to modulate anti-inflammatory cytokines make this receptor a new interesting therapeutic target for neuroinflammation regulation. In this review, we summarize the distribution and physiological functions of the α7 nicotinic receptor in glial cells (astrocytes and microglia) and its role in the modulation of neuroinflammation. Moreover, we explore how its altered expression and function contribute to the development of different neurological pathologies and exacerbate neuroinflammatory processes.


Assuntos
Encéfalo/patologia , Colinérgicos/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Animais , Humanos , Neuroglia/metabolismo , Neuroglia/patologia , Transdução de Sinais , Receptor Nicotínico de Acetilcolina alfa7/química
16.
Artigo em Inglês | MEDLINE | ID: mdl-33808259

RESUMO

In recent years, lipid metabolism has gained greater attention in several diseases including cancer. Dysregulation of fatty acid metabolism is a key component in breast cancer malignant transformation. In particular, de novo lipogenesis provides the substrate required by the proliferating tumor cells to maintain their membrane composition and energetic functions during enhanced growth. However, it appears that not all breast cancer subtypes depend on de novo lipogenesis for fatty acid replenishment. Indeed, while breast cancer luminal subtypes rely on de novo lipogenesis, the basal-like receptor-negative subtype overexpresses genes involved in the utilization of exogenous-derived fatty acids, in the synthesis of triacylglycerols and lipid droplets, and fatty acid oxidation. These metabolic differences are specifically associated with genomic and proteomic changes that can perturb lipogenic enzymes and related pathways. This behavior is further supported by the observation that breast cancer patients can be stratified according to their molecular profiles. Moreover, the discovery that extracellular vesicles act as a vehicle of metabolic enzymes and oncometabolites may provide the opportunity to noninvasively define tumor metabolic signature. Here, we focus on de novo lipogenesis and the specific differences exhibited by breast cancer subtypes and examine the functional contribution of lipogenic enzymes and associated transcription factors in the regulation of tumorigenic processes.


Assuntos
Neoplasias da Mama , Lipogênese , Ácidos Graxos , Humanos , Metabolismo dos Lipídeos , Proteômica
17.
Nanomaterials (Basel) ; 11(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809596

RESUMO

Vitamin B12 (VitB12) is a naturally occurring compound produced by microorganisms and an essential nutrient for humans. Several papers highlight the role of VitB12 deficiency in bone and heart health, depression, memory performance, fertility, embryo development, and cancer, while VitB12 treatment is crucial for survival in inborn errors of VitB12 metabolism. VitB12 is administrated through intramuscular injection, thus impacting the patients' lifestyle, although it is known that oral administration may meet the specific requirement even in the case of malabsorption. Furthermore, the high-dose injection of VitB12 does not ensure a constant dosage, while the oral route allows only 1.2% of the vitamin to be absorbed in human beings. Nanocarriers are promising nanotechnology that can enable therapies to be improved, reducing side effects. Today, nanocarrier strategies applied at VitB12 delivery are at the initial phase and aim to simplify administration, reduce costs, improve pharmacokinetics, and ameliorate the quality of patients' lives. The safety of nanotechnologies is still under investigation and few treatments involving nanocarriers have been approved, so far. Here, we highlight the role of VitB12 in human metabolism and diseases, and the issues linked to its molecule properties, and discuss how nanocarriers can improve the therapy and supplementation of the vitamin and reduce possible side effects and limits.

18.
Adv Exp Med Biol ; 1295: 3-27, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33543453

RESUMO

Clinical responses and tolerability of conventional nanocarriers (NCs) are sometimes different from those expected in anticancer therapy. Thus, new smart drug delivery systems (DDSs) with stimuli-responsive properties and novel materials have been developed. Several clinical trials demonstrated that these DDSs have better clinical therapeutic efficacy in the treatment of many cancers than free drugs. Composition of DDSs and their surface properties increase the specific targeting of therapeutics versus cancer cells, without affecting healthy tissues, and thus limiting their toxicity versus unspecific tissues. Herein, an extensive revision of literature on NCs used as DDSs for cancer applications has been performed using the available bibliographic databases.


Assuntos
Nanopartículas , Neoplasias , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/tratamento farmacológico
19.
Nanomaterials (Basel) ; 11(1)2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33406805

RESUMO

Ufasomes are unsaturated fatty acid liposomes made up of oleic and linoleic acids, natural components required in various biological processes. This kind of nanocarrier is characterized by a simple and dynamic structure and is able to improve the bioavailability of unsaturated fatty acids. The aim of this investigation was to evaluate ufasomes as natural compound delivery systems to deliver oleuropein and improve its antioxidant activity. Oleuropein is a phenolic compound mainly present in olives and olive oil, with several biological properties, such as the antioxidant activity. However, to improve their biological activity, antioxidant compounds should be able to cross cell membranes and uniformly incorporate in cells. Because of the great similarity between their constituents and cell membranes, ufasomes could be advantageous carriers for oleuropein delivery. The physico-chemical characteristics of ufasomes were investigated. A regular shape was shown by transmission electron microscopy studies, while the mean sizes were dependent on the ufasomes composition. In vitro studies highlighted that empty ufasomes did not lead to cell mortality at the tested concentrations and a good carrier internalization in CaCo-2 cells, further studies in vitro studies demonstrated that oleuropein-loaded ufasomes were able to enhance the antioxidant activity of the free active substance making this carrier a suitable one for nutraceutical application.

20.
Front Toxicol ; 3: 636640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35295124

RESUMO

Micro and nanoplastics are fragments with dimensions less than a millimeter invading all terrestrial and marine environments. They have become a major global environmental issue in recent decades and, indeed, recent scientific studies have highlighted the presence of these fragments all over the world even in environments that were thought to be unspoiled. Analysis of micro/nanoplastics in isolated samples from abiotic and biotic environmental matrices has become increasingly common. Hence, the need to find valid techniques to identify these micro and nano-sized particles. In this review, we discuss the current and potential identification methods used in microplastic analyses along with their advantages and limitations. We discuss the most suitable techniques currently available, from physical to chemical ones, as well as the challenges to enhance the existing methods and develop new ones. Microscopical techniques (i.e., dissect, polarized, fluorescence, scanning electron, and atomic force microscopy) are one of the most used identification methods for micro/nanoplastics, but they have the limitation to produce incomplete results in analyses of small particles. At present, the combination with chemical analysis (i.e., spectroscopy) overcome this limit together with recently introduced alternative approaches. For example, holographic imaging in microscope configuration images microplastics directly in unfiltered water, thus discriminating microplastics from diatoms and differentiates different sizes, shapes, and plastic types. The development of new analytical instruments coupled with each other or with conventional and innovative microscopy could solve the current problems in the identification of micro/nanoplastics.

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