coagulation pathways that ultimately cause the symptoms and signs of preeclampsia.
Based on the complex nature of the origin of pre- eclampsia, we hypothesize that placental and maternal cells cross-talk, mediated by extracellularvesicles (EVs), contributes to the initiation and progression of preeclamp- sia in women, both with and without known pre-existing risk factors (Fig. 1 ). In women for whom EVs derived from the placenta are the major contributors, we propose that the symptoms of preeclampsia may appear earlier in gestation. If EVs derived from maternal cells are the major contributors, the symptoms may appear later in gestation. Two distinct types of EVs (exosomes and microvesicles) are released by almost all activated cells or cells involved in pathophysiological processes [ 10 – 13 ]. Exosomes and microvesicles differ in size and their modes of formation. Exosomes are smaller than microvesicles (30–120 nm vs. 40–1000 nm) [ 12 ], and are formed by the endocytosis of multivesicular bodies and are released from cells by exo- cytosis. In contrast, microvesicles (MVs) are membrane- bound vesicles that are shed from the plasma membrane [ 12 ]. Despite these differences, the size ranges for these two distinct classes of EVs overlap in some extent, and there are currently no established methods available to distinguish them purely on basis of size. Surface-specific EV markers that can be used to differentiate microvesicles and exosomes have not yet been identified. We have there- fore used the term EVs, as previously suggested by the scientific community [ 14 ], to refer to exosomes and microvesicles in this review.
To test whether FhEVs could prevent colitis, C57BL/6 mice were injected subcutaneously with 10 µ g of FhEVs/mouse/injection on days 0, 15, and 30 before colitis induction by DSS at day 42 (Figure 1B). We used these amounts of EVs based on previous studies (Trelis et al., 2016). FhEVs- treated mice were considerably less susceptible to DSS-induced colitis and lost around 10% of their initial body weight, whereas non-treated mice lost around 20% after 7 days of DSS treatment (data not shown). Accordingly, DAI of FhEVs-treated colitic mice was lower than in colitic mice on day 5 after the initiation of DSS treatment. Moreover, this difference gradually increased over time (Figure 1C). On autopsy, a significant colonic shortening was detected in the DSS-administered groups as compared to the water-administered ones injected or not with FhEVs. However, between DSS-treated mice, FhEVs injected mice had significant larger colons than their non-injected counterparts (Figures 1D,E).
Basal physiological concentration of adenosine at the extracellular space is reported as 30-200 nmol/L (Chen et al., 2013; Fredholm, 2014; Idzko et al., 2014). However, under pathological conditions such as hypoxia, ischemia, or inflammation, adenosine level could reach up to ~1 µmol/L as a result of increased release and generation from adenine nucleotides (Ballarin et al., 1991; Eltzschig, 2009; Chen et al., 2013; Fredholm, 2014; Idzko et al., 2014). Since these pathological conditions also result in increased extracellular ATP reaching 4-8 mmol/L, CD39 and CD73 activity could contribute to further increase extracellular adenosine generation (Chen et al., 2013). Adenosine release takes place in multiple cell types including endothelial cells, astrocytes, cardiomyocytes, neutrophils, and trophoblast cells (Fredholm, 2014). However, the main source of adenosine in plasma is ADP and ATP released from activated platelets (Eltzschig, 2013; Idzko et al., 2014). Thus, besides that determination of adenosine concentration is an important point, it is necessary to take into account that determination of this nucleoside’s concentration in blood may by altered by nucleotide release from platelets during blood sampling, a phenomenon that per
with melanoma, multiple myeloma, prostate cancer, hepatocellular carcinoma or head and neck cancer (40, 135-138).
In the bone marrow of healthy mice, the CD11b + Gr-1 + population comprises 20–30% of all cells. However, CD11b + Gr-1 + cells make up only a small proportion (2–4%) of spleen cells and are absent from the lymph nodes (132). MDSCs accumulate in the bone marrow, spleen and peripheral blood, within primary and metastatic solid tumors, and to a lesser extent in lymph nodes. Tumors release multiple soluble factors, causing substantial alterations in the differentiation and function of myeloid cells. Cytokines such as GM‑CSF, G‑CSF, M‑CSF, stem cell factor (SCF), vascular endothelial growth factor (VEGF) and IL‑3 not only promote myelopoiesis but also block myeloid cell maturation (132, 139). Tumor-derived pro- inflammatory factors (e.g. IL-1β, IL-6, S100A8 and S100A9), as well as cytokines released by activated T cells (such as IFNγ, IL-4, IL-10 and IL-13) convert IMCs into MDSCs (140). The tumor-derived factors CCL2, CCL12, CXC-chemokine ligand 5, prokineticin 2, S100A8 and S100A9 attract MDSCs to the tumor bed (40, 141). Interestingly, MDSCs can also be recruited by nitrated or nitrosylated CCL2, whereas effector CD8 T cells cannot, which may account for the selective accumulation of myelomonocytic cells within murine and human tumors (142). Lypopolisaccharide (LPS), in combination with IFN-γ, promotes MDSC expansion, probably through the inhibition of DC differentiation (143). Tumor-derived TGF-β also regulates MDSC accumulation and neutrophil polarization (144, 145). Tumors can also promote MDSC expansion through the release of small membrane vesicles – exosomes that contain signaling peptides, mRNAs, microRNAs and lipids (146).
saline solution, 0.9% NaCl). After 19 days, mice were injected with 100 μL of either DiR-labeled EVs (10 μg), EV-AuNP (0.5 nM, 10 μg of protein), AuNP-PEG-FA (0.5 nM) or PBS. After another 24 h the animals were necropsied and organs were visualized using the In- Vivo FX PRO imaging system (Bruker). Black tissue was separated from the rest of the lung and weighed. Metas- tasis was expressed as black tissue mass/total lung mass in percent (%) post-fixation, as previously described . Organs and a section of metastatic lung tumor nodules were then lyophilized for gold NAA analysis as described above. In parallel, a section of extracted lungs was fixed (PFA 4%) for 48 h at 4 °C, embedded in paraffin and sectioned at 5 μM using a microtome for gold nucleation analysis as previously described . Briefly, tissues were deparaffinized, hydrated and treated with Retrieval solution (DAKO, Rune Lind- ing) at 100 °C for 20 min. The slices were then washed with PBS, 50 nM glycine, 0.1% gelatin and water. Tis- sues were then allowed to react for 15 min with 200 μL of Gold Enhanced ™ LM (Nanoprobes) and rinsed with water to stop gold nucleation. Finally, samples were stained with Contrast BLUE solution and mounted with DAKO mounting solution. These experiments were repeated three times. To observe gold nucleation, at least five digital images were obtained per sample by light microscopy using 40–100× magnification and identical camera ettings.
To clarify the role of miR-21, MSCs from the pre-pubertal group were transiently transfected with miRVana miR-21-5p, and its expression was verified by qRT-PCR (Fig. 5A). The transfected cells expressed statistically significantly lower levels of miR-21 (P < 0.05) than the same cells transfected with a mimic miRNA used as con- trol. qRT-PCR analysis of DAMPS associated with TLR4 indicated that miR-21 inhibition produced a statistically significant decrease in S100A4, S100A6 and HMGB1 with respect to the MSC control (Fig. 5C,D,E). Afterwards expression of IL-6 and IL-1β , associated to TLR4 pathway, were statistically significant decreased produced by miR-21 inhibition (Fig. 5G,H). EV isolation from the cells was not possible due to the nature of transient trans- fections. BM-MSCs from the adult group have less therapeutic capacity due to TLR4-mediated regulation of bone marrow MSC proliferation and osteogenic differentiation through Wnt3a and Wnt5a signalling 42 . Conversely,
significant differences influenced by the donor age . We also demonstrated that immune profiles of MSC-derived EVs have age-dependent differences and they can be modi- fied using miRNA . The mammalian target of rapamycin (mTOR) is an amino acid sensor which perceives and in- corporates different environmental signals. mTOR balances cell growth and nutrient availability and contributes to deci- sions on stem cell fate as a consequence of endogenous DNA damage . mTOR also regulates cellular senescence and drives the infrastructure of bioenergetics . Rapamy- cin inhibits the senescence effect produced by mTOR, which is mediating MSC proliferation potential through its effect on their self-renewal loss . There are two signalling complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC2 plays an important role in endothelial senescence, evident by an increase in binding of Rictor, which is an essential component of mTORC2- directed phosphorylation of mTOR at Ser2481 and AKT (phosphor-AKT), producing an increase of β-galactosidase staining in senescence . MicroRNA (miR)-188-3p has been shown to be a key regulator of age-associated bone loss in the bone marrow through its target on Rictor , and insights into the mechanism involved in MSC ageing suggest that interventions with miRNAs could modify the function of MSCs and their derived extracellularvesicles . This study assessed whether EVs could modify MSC markers of ageing in vitro and whether Rictor has a key role through the mTORC2 pathway involving the ageing process.
neuron– glia unit, including contact- mediated signaling andextracellular free ligands. Recently, another regulatory mech- anism has emerged in which a cell releases vesicles containing RNAs and proteins that are taken up and incorporated into the target recipient cell (Simons and Raposo, 2009). Vesicular-mediated trans- fer of molecular cargoes between glial cells and neurons has been described in the nervous system (Lopez-Verrilli and Court, 2012, 2013a). We have demon- strated vesicular-mediated transfer of ri- bosomes from SCs, the peripheral glial cell type, to axons in vivo after axonal damage as well as during axonal regeneration (Court et al., 2008, 2011). Recently, we found that exosomes secreted by SCs and selectively internalized by axons increase neurite growth substantially and greatly enhance axonal regeneration in vitro and in vivo (Lopez-Verrilli et al., 2013b). The F.A.C. laboratory is now using a combina- tion of next-generation sequencing, pro- teomics, and bioinformatic analysis to identify RNAs and proteins present in SC exosomes, and searching for candidates mediating the functional effect of SC exosomes on axonal regen- eration. Preliminary analysis demonstrates that mRNA and miRNA are selectively loaded into SC exosomes, and some of the mRNA present in these exosomes encode neuronal-specific pro- teins. In addition, SC exosomes trigger a broad change in the transcriptional profile of recipient neurons, revealing novel growth-associated pathways triggered by these vesicles. This mode of interaction provides a new dimension to the under- standing of the intercellular regulation at large, with the pre- diction that a number of phenomena of the nervous system, which are still poorly understood, will be revealed under this new light.
Factores dietéticos, incluyendo deficiencias de vitaminas
Actualmente se entiende que la preeclampsia es un síndrome con dos etapas, la primera de ellas siendo altamente variable, lo cual predispone a la placenta a la hipoxia, seguido por la liberación de factores solubles que resultan en muchos de los fenómenos observados clínicamente. Algunas de las teorías más anticuadas pueden ser adoptadas por estas etapas, precisamente porque los factores solubles son las causantes de las lesiones clásicas, como las del endotelio, del riñón, inflamatorias, etc. La susceptibilidad materna es sin duda una de las variables involucradas en la instalación del síndrome.
aspectos relacionados con preeclampsia, se eligieron los 16 artículos más recientes, los cuales presentan menos de 5 años desde su publicación. Se logró sintetizar las principales y más actuales ideas necesarias para tener un enfoque clínico general de esta patología, lo cual busca permitir conocer y poner en práctica las principales herramientas que existen para abordar un caso relacionado con este trastorno hipertensivo y así obtener los mejores resultados.
The majority of research on how different biomaterial interactions can alter stem cell behaviour has been performed on cells from non-dental origin. However, dental stem cells have been used in combination with biomaterial surfaces in some investigations. A recent study demonstrated that tooth formation in vivo could be achieved by seeding dissociated tooth cells on a scaffold material and implanting the constructs into the omentum of immunocompromised rats (Sumita et al, 2006). This study reported that a collagen sponge scaffold allowed tooth production with a higher degree of success than using a poly-glycolic acid fibre scaffold. The tissue arrangement of the teeth formed from collagen scaffolds has been demonstrated to be improved by the sequential seeding of the scaffold with epithelial and mesenchymal cells (Honda et al, 2007). Another study has also demonstrated that it is possible to produce pulp-like connective tissue by seeding SHED and human endothelial cells on a biodegradable poly-L-lactic acid scaffold in an in vivo tooth slice model (Cordeiro et al, 2008). Combined these studies provide evidence that there is the potential for dental cells to be used in combinations with biomaterials for dental regeneration.
Contacto con animales dom(sticos ?noA en caso afirmatio! especificar VCu$lesWUUUUUU E#istencia de hacinamiento en el hogar ?noA UUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUU E#istencia de factores de riesgo en la comunidad! hogar & laboral ?noA en caso afirmatio! especificar VCu$lesWUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUU E#istencia de alteraciones físicas o mentales en la usuaria que pueden desencadenar un accidente ?siA en caso afirmatio! especificar VCu$lesW +or motio del embarazo sufre de preeclampsia lee lo que le altera el estado emocional & temorUUUUUUUUUUUUUUUUUUUU +ercepción de la usuaria de su estado de salud actual! especificar2 siente temor debido a que se le realizara una cesarea & tendr$ que quedar internadaUUUUUUUUUUUUUUUUUUUUUU nter(s por el cuidado de salud ?siA es caso negatio especificar V+or qu(W UUUUUUUUUUUU ,sistencia o control prenatal ?siA en caso negatio! especificar V+or qu(W UUUUUUUUUUUUU en caso afirmatio! especificar Vcon quien acudeW & Vnumero de isitasW ,cude al centro de salud acompañada de su madrina o en ocasiones con su esposoUUUUUUUUUUUUUUUUU -ratamiento medico en el hogar! especificar VCu$lW 0o recuerda que tratamiento es el que le daban para el control de infección de ías urinariasUUUUUUUUUUUUUUUUUUUUUUUUU <eguimiento de tratamiento medico ?siA en caso negatio! especificar V+or qu(W UUUUUUU UUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUU UUUUUUUUUUUUUUUU
Abstract: The potential role of the fungi, isolated from the peanut rhizosphere, in the production of extracellu- lar and intracellular acid and alkaline phosphatase, was evaluated in vitro. Acid and alkaline extracellular phos- phatases showed the highest activities, and the Penicillium species were the most efficient in their production. The correlation analysis showed that extracellular acid and intracellular acid phosphatase produced by Aspergillus niger, A. terreus, Penicillium sp. y P. brevicompactum were negatively correlated; while the extra- cellular and intracellular phosphatase activities, were positively correlated. The extracellular acid phosphatase activities produced in vitro by majority of fungi assayed, were not correlated with the acid phosphatase activity present in the peanut soil rhizosphere. Nevertheless, the extracellular alkaline phosphatase activities produced in vitro, were negatively correlated with the extracellular alkaline phosphatase activities present in the rhizosphere. The ability of phosphatase production by fungi isolated from peanut rhizosphere suggests they have great poten- tial to contribute to the P mineralization in this zone.
Con base en la fisiopatología de la preeclampsia pos- parto, se deduciría que parte del tratamiento de esta pato- logía incluye suspender el empleo de AINEs, sustituyéndo- los por dosis bajas o intermedias de acetaminofén y/u opioides para el manejo del dolor, con lo cual en la mayo- ría de los casos se obtienen resultados satisfactorios. En algunos otros casos serán necesarios diuréticos a fin de lo- grar un balance hídrico neutro en los casos en que exista sobrecarga de volumen, y finalmente, también se incluye el empleo de antihipertensivos que pueden ser requeridos por periodos cortos. 17
bioactive compounds, such as hydroxytyrosol. Previously, we demonstrated that hydroxytyrosol inhibits angiogenesis in vitro. The present study aimed to: i) get further insight into the effects of hydroxytyrosol on extracellular matrix remodeling; and ii) test whether hydroxytyrosol is able to inhibit angiogenesis ex vivo and in vivo. Hydroxytyrosol induced a shift toward inhibition of proteolysis in endothelial cells, with decreased expression of extracellular matrix remodeling-enzyme coding genes and increased levels of some of their inhibitors. Furthermore, this work demonstrated that hydroxytyrosol, at concentrations within the range of its content in virgin olive oil that can be absorbed from moderate and sustained virgin olive oil consumption, is a strong inhibitor of
Because of these reasons, we would like to argue that this emerging field of research can be described as “nanobiodiversity”: the study of extracellular nano- structures. How are ENS formed? How have they evolved? Are they directly encoded in the genome or are they the result of some cellular emergent prop- erty? What kind of mathematical or developmental principles explain the origin of ENS? These are some questions that can be addressed by investigating the nanobiodiversity of our world. This review is not intended to be exhaustive. We intend to provide sim- ple and brief examples of the most investigated extra- cellular nanostructures using original images of Costa Rican biodiversity. At the end, we provide a general description of the questions that arise when these phe- nomena are observed under the unifying concept of nanobiodiversity.
La preeclampsia es la patología, en donde la hipertensión arterial puede presentarse en el embarazo, cuyo origen está relacionada con alteraciones en la placenta. Estas alteraciones van a dar origen a una disfunción de los vasos sanguíneos maternos de mujeres susceptibles. Aunque el cuadro más característico de la enfermedad viene a ser el aumento de la presión arterial, lo cual puede llevar a una eclampsia, ocasionando daños en los riñones, hígado y cerebro (8).
RESULTADOS: El perfil sociodemográfico de los 270 pacientes con y sin preeclampsia fueron de edad promedio 27.5 ± 7.5 años, se encontró la mayoría entre los 19 a 34 años (65.6%). El 75.2% de las pacientes eran convivientes con educación secundaria (54.8%). Se observó que la nuliparidad se relaciona con la presencia de preeclampsia (p<0.001). Asimismo se observa relación entre el tipo de parto por cesárea (p<0.001), el antecedente personal de preeclampsia (p<0.001), el antecedente de hipertensión arterial crónica (p<0.001), el antecedente de algún trastorno hipertensivo en la gestación (p<0.001), el consumo de sustancias nocivas (p<0.001), el nivel de aspartato aminotransferasa >18 (p<0.001), el ácido úrico >5.3 mg/dl (p<0.001) y el grupo de pacientes con o sin preeclampsia. El valor estimado del OR para las variables que tienen relación son: nuliparidad OR=3.31, antecedente personal de preeclampsia OR=2.42, antecedente de hipertensión arterial crónica OR=11.0, antecedente de algún trastorno hipertensivo en la gestación OR=2.78, consumo de sustancias nocivas OR=1.98.