Calcium and Neural Stem Cell Proliferation.

Intracellular calcium plays a pivotal role in central nervous system (CNS) development by regulating various processes such as cell proliferation, migration, differentiation, and maturation. However, understanding the involvement of calcium (Ca2+) in these processes during CNS development is challenging due to the dynamic nature of this cation and the evolving cell populations during development. While Ca2+ transient patterns have been observed in specific cell processes and molecules responsible for Ca2+ homeostasis have been identified in excitable and non-excitable cells, further research into Ca2+ dynamics and the underlying mechanisms in neural stem cells (NSCs) is required. This review focuses on molecules involved in Ca2+ entrance expressed in NSCs in vivo and in vitro, which are crucial for Ca2+ dynamics and signaling. It also discusses how these molecules might play a key role in balancing cell proliferation for self-renewal or promoting differentiation. These processes are finely regulated in a time-dependent manner throughout brain development, influenced by extrinsic and intrinsic factors that directly or indirectly modulate Ca2+ dynamics. Furthermore, this review addresses the potential implications of understanding Ca2+ dynamics in NSCs for treating neurological disorders. Despite significant progress in this field, unraveling the elements contributing to Ca2+ intracellular dynamics in cell proliferation remains a challenging puzzle that requires further investigation.

Cancer Stem Cells and Androgen Receptor Signaling: Partners in Disease Progression.

Cancer stem cells exhibit self-renewal, tumorigenesis, and a high differentiation potential. These cells have been detected in every type of cancer, and different signaling pathways can regulate their maintenance and proliferation. Androgen receptor signaling plays a relevant role in the pathophysiology of prostate cancer, promoting cell growth and differentiation processes. However, in the case of prostate cancer stem cells, the androgen receptor negatively regulates their maintenance and self-renewal. On the other hand, there is evidence that androgen receptor activity positively regulates the generation of cancer stem cells in other types of neoplasia, such as breast cancer or glioblastoma. Thus, the androgen receptor role in cancer stem cells depends on the cellular context. We aimed to analyze androgen receptor signaling in the maintenance and self-renewal of different types of cancer stem cells and its action on the expression of transcription factors and surface markers associated with stemness.

Pluripotent Stem Cells as a Model for Human Embryogenesis.

Pluripotent stem cells (PSCs; embryonic stem cells and induced pluripotent stem cells) can recapitulate critical aspects of the early stages of embryonic development; therefore, they became a powerful tool for the in vitro study of molecular mechanisms that underlie blastocyst formation, implantation, the spectrum of pluripotency and the beginning of gastrulation, among other processes. Traditionally, PSCs were studied in 2D cultures or monolayers, without considering the spatial organization of a developing embryo. However, recent research demonstrated that PSCs can form 3D structures that simulate the blastocyst and gastrula stages and other events, such as amniotic cavity formation or somitogenesis. This breakthrough provides an unparalleled opportunity to study human embryogenesis by examining the interactions, cytoarchitecture and spatial organization among multiple cell lineages, which have long remained a mystery due to the limitations of studying in utero human embryos. In this review, we will provide an overview of how experimental embryology currently utilizes models such as blastoids, gastruloids and other 3D aggregates derived from PSCs to advance our understanding of the intricate processes involved in human embryo development.

Increased Nuclear FOXP2 Is Related to Reduced Neural Stem Cell Number and Increased Neurogenesis in the Dorsal Telencephalon of Embryos of Diabetic Rats through Histamine H1 Receptors.

Diabetic rat embryos have increased cortical neurogenesis and neuron maturation, and their offspring presented altered neuron polarity, lamination, and diminished neuron excitability. The FOXP2 overexpression results in higher cortical neurogenesis by increasing the transition of radial glia to the intermediate progenitor. Similarly, histamine through H1-receptor activation increases cortical neuron differentiation. Indeed, blocking the H1-receptor by the systemic administration of chlorpheniramine to diabetic pregnant rats prevents increased neurogenesis. Here, we explore the relationship between the H1-receptor and FOXP2 on embryo neurogenesis from diabetic dams. Through qRT-PCR, Western blot, immunohistofluorescence, and flow cytometry, we showed an increased FOXP2 expression and nuclear localization, a reduced Nestin expression and -positive cells number, and a higher PKCα expression in the cortical neuroepithelium of fourteen-day-old embryos from diabetic rats. Interestingly, this scenario was prevented by the chlorpheniramine systemic administration to diabetic pregnant rats at embryo day twelve. These data, together with the bioinformatic analysis, suggest that higher H1-receptor activity in embryos under high glucose increases FOXP2 nuclear translocation, presumably through PKCα phosphorylation, impairing the transition of radial glia to intermediate progenitor and increasing neuron differentiation in embryos of diabetic rats.

Recent advances in the use of CRISPR/Cas for understanding the early development of molecular gaps in glial cells.

Glial cells are non-neuronal elements of the nervous system (NS) and play a central role in its development, maturation, and homeostasis. Glial cell interest has increased, leading to the discovery of novel study fields. The CRISPR/Cas system has been widely employed for NS understanding. Its use to study glial cells gives crucial information about their mechanisms and role in the central nervous system (CNS) and neurodegenerative disorders. Furthermore, the increasingly accelerated discovery of genes associated with the multiple implications of glial cells could be studied and complemented with the novel screening methods of high-content and single-cell screens at the genome-scale as Perturb-Seq, CRISP-seq, and CROPseq. Besides, the emerging methods, GESTALT, and LINNAEUS, employed to generate large-scale cell lineage maps have yielded invaluable information about processes involved in neurogenesis. These advances offer new therapeutic approaches to finding critical unanswered questions about glial cells and their fundamental role in the nervous system. Furthermore, they help to better understanding the significance of glial cells and their role in developmental biology.

Prolactin from Pluripotency to Central Nervous System Development.

Prolactin (PRL) is a versatile hormone that exerts more than 300 functions in vertebrates, mainly associated with physiological effects in adult animals. Although the process that regulates early development is poorly understood, evidence suggests a role of PRL in the early embryonic development regarding pluripotency and nervous system development. Thus, PRL could be a crucial regulator in oocyte preimplantation and maturation as well as during diapause, a reversible state of blastocyst development arrest that shares metabolic, transcriptomic, and proteomic similarities with pluripotent stem cells in the naïve state. Thus, we analyzed the role of the hormone during those processes, which involve the regulation of its receptor and several signaling cascades (Jak/Mapk, Jak/Stat, and PI3k/Akt), resulting in either a plethora of physiological actions or their dysregulation, a factor in developmental disorders. Finally, we propose models to improve the knowledge on PRL function during early development.

Increased Levels of Plasma Extracellular Heat-Shock Proteins 60 and 70 kDa Characterized Early-Onset Neonatal Sepsis.

Background: Extracellular heat-shock proteins (eHsp) are highly conserved molecules that play an important role in inflammatory diseases and have been quantified in plasma from patients with infectious diseases, including sepsis. There is a constant search for dependable biochemical markers that, in combination with conventional methods, could deliver a prompt and reliable diagnosis of early-onset neonatal sepsis. Objective: We sought to assess the level of eHsp-27, eHsp-60, eHsp-70, and tumor necrosis factor-alpha (TNFα) in plasma of healthy neonates at term and infants with early-onset neonatal sepsis. Methods: This study included 34 newborns that were classified as healthy neonates at term (blood samples from the umbilical cord, n = 23) or infants with early-onset neonatal sepsis (blood samples obtained from umbilical artery by standard sterile procedures before starting a systemic antibiotic intervention, n = 11). All blood samples were centrifuged, and the plasma recovered to determine eHsp-27, eHsp-60, eHsp-70, and TNFα levels by ELISA. Results: Our results indicate that the level of eHsp-27 in healthy neonates at term was 0.045 ± 0.024 pg/ml. This value decreased 2.5-fold in infants with early-onset neonate sepsis (0.019 ± 0.006 pg/ml, p = 0.004). In contrast, the levels of eHsp-60 and eHsp-70 in healthy neonates at term were 13.69 ± 5.3 and 4.03 ± 2.6 pg/ml, respectively. These protein levels increased significantly 1.8- and 1.9-fold in the plasma of infants with early-onset neonatal sepsis (p ≤ 0.001). The level of TNFα in healthy neonates at term was 2.94 ± 0.46 pg/ml, with a 3.0-fold increase in infants with early-onset neonatal sepsis (8.96 ± 0.72 pm/ml, p ≤ 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of eHsp compared with that of C-reactive protein were 73.3, 60.0, 47.8, and 33.3%, respectively. Conclusion: This study demonstrated a consistent increase of eHsp-60 and eHsp-70 in the plasma of infants diagnosed with early-onset neonatal sepsis. These proteins showed higher sensitivity and specificity than C-reactive protein and blood culture test.

Differential localization of serotoninergic system elements in human amniotic epithelial cells†.

Serotonin or 5-hydroxytryptamine (5-HT) is a biogenic amine involved in regulating several functions, including development. However, its impact on human embryo development has been poorly studied. The present work investigated the expression and distribution of the main components of the serotoninergic system in human amniotic tissue and human amniotic epithelial cells (hAEC) in vitro, as an alternative model of early human embryo development. Amniotic membranes from full-term healthy pregnancies were used. Human amnion tissue or hAEC isolated from the amnion was processed for reverse transcription-polymerase chain reaction and immunofluorescence analyses of the main components of the serotoninergic system. We found the expression of tryptophan hydroxylase type 1 (TPH1), type 2 (TPH2), serotonin transporter (SERT), monoamine oxidase-A (MAOA), as well as HTR1D and HTR7 receptors at mRNA level in amnion tissue as well in hAEC. Interestingly, we found the presence of 5-HT in the nucleus of the cells in amnion tissue, whereas it was located in the cytoplasm of isolated hAEC. We detected TPH1, TPH2, and HTR1D receptor in both the nucleus and cytoplasm. SERT, MAOA, and HTR7 receptor were only observed in the cytoplasm. The results presented herein show, for the first time, the presence of the serotoninergic system in human amnion in vivo and in vitro.

Long-Term Functional and Cytoarchitectonic Effects of the Systemic Administration of the Histamine H1 Receptor Antagonist/Inverse Agonist Chlorpheniramine During Gestation in the Rat Offspring Primary Motor Cortex.

The transient histaminergic system is among the first neurotransmitter systems to appear during brain development in the rat mesencephalon/rhombencephalon. Histamine increases FOXP2-positive deep-layer neuron differentiation of cortical neural stem cells through H1 receptor activation in vitro. The in utero or systemic administration of chlorpheniramine (H1 receptor antagonist/inverse agonist) during deep-layer cortical neurogenesis decreases FOXP2 neurons in the developing cortex, and H1R- or histidine decarboxylase-knockout mice show impairment in learning and memory, wakefulness and nociception, functions modulated by the cerebral cortex. Due to the role of H1R in cortical neural stem cell neurogenesis, the purpose of this study was to evaluate the postnatal impact of the systemic administration of chlorpheniramine during deep-layer cortical neuron differentiation (E12-14) in the primary motor cortex (M1) of neonates (P0) and 21-day-old pups (P21). Chlorpheniramine or vehicle were systemically administered (5 mg/kg, i.p.) to pregnant Wistar rats at gestational days 12-14, and the expression and distribution of deep- (FOXP2 and TBR1) and superficial-layer (SATB2) neuronal cortical markers were analyzed in neonates from both groups. The qRT-PCR analysis revealed a reduction in the expression of Satb2 and FoxP2. However, Western blot and immunofluorescence showed increased protein levels in the chlorpheniramine-treated group. In P21 pups, the three markers showed impaired distribution and increased immunofluorescence in the experimental group. The Sholl analysis evidenced altered dendritic arborization of deep-layer neurons, with lower excitability in response to histamine, as evaluated by whole-cell patch-clamp recording, as well as diminished depolarization-evoked [3H]-glutamate release from striatal slices. Overall, these results suggest long-lasting effects of blocking H1Rs during early neurogenesis that may impact the pathways involved in voluntary motor activity and cognition.

Role of serotonin in vertebrate embryo development.

Since its discovery in 1937, serotonin (5-HT) has become one of the most studied biogenic amines due to its predominant role in regulating several physiological processes such as mood, sleep, and food intake. This amine and the main components of the serotoninergic system are in almost all cells of the body. The presence of 5-HT and the serotoninergic system has been observed in oocytes and in different embryo development stages of fish, amphibians, birds, and mammals. In several classes of vertebrates, the change in the concentration of 5-HT or the alteration of the serotoninergic system, interfere with early embryo development. These data suggest that 5-HT participates in embryo development of vertebrates.

Impaired Cortical Cytoarchitecture and Reduced Excitability of Deep-Layer Neurons in the Offspring of Diabetic Rats.

Maternal diabetes has been related to low verbal task scores, impaired fine and gross motor skills, and poor performance in graphic and visuospatial tasks during childhood. The primary motor cortex is important for controlling motor functions, and embryos exposed to high glucose show changes in cell proliferation, migration, and differentiation during corticogenesis. However, the existing studies do not discriminate between embryos with or without neural tube defects, making it difficult to conclude whether the reported changes are related to neural tube defects or other anomalies. Furthermore, postnatal effects on central nervous system cytoarchitecture and function have been scarcely addressed. Through molecular, biochemical, morphological, and electrophysiological approaches, we provide evidence of impaired primary motor cerebral cortex lamination and neuronal function in pups from diabetic rats, showing an altered distribution of SATB2, FOXP2, and TBR1, impaired cell migration and polarity, and decreased excitability of deep-layer cortical neurons, suggesting abnormalities in cortico-cortical and extra-cortical innervation. Furthermore, phase-plot analysis of action potentials suggests changes in the activity of potassium channels. These results indicate that high-glucose insult during development promotes complex changes in migration, neurogenesis, cell polarity establishment, and dendritic arborization, which in turn lead to reduced excitability of deep-layer cortical neurons.

Unprecedented Potential for Neural Drug Discovery Based on Self-Organizing hiPSC Platforms.

Human induced pluripotent stem cells (hiPSCs) have transformed conventional drug discovery pathways in recent years. In particular, recent advances in hiPSC biology, including organoid technologies, have highlighted a new potential for neural drug discovery with clear advantages over the use of primary tissues. This is important considering the financial and social burden of neurological health care worldwide, directly impacting the life expectancy of many populations. Patient-derived iPSCs-neurons are invaluable tools for novel drug-screening and precision medicine approaches directly aimed at reducing the burden imposed by the increasing prevalence of neurological disorders in an aging population. 3-Dimensional self-assembled or so-called 'organoid' hiPSCs cultures offer key advantages over traditional 2D ones and may well be gamechangers in the drug-discovery quest for neurological disorders in the coming years.

iPSC for modeling neurodegenerative disorders.

Neurodegenerative disorders such as Parkinson's and Alzheimer's disease, are fundamental health concerns all around the world. The development of novel treatments and new techniques to address these disorders, are being actively studied by researchers and medical personnel. In the present review we will discuss the application of induced Pluripotent Stem Cells (iPSCs) for cell-therapy replacement and disease modelling. The aim of iPSCs is to restore the functionality of the damaged tissue by replacing the impaired cells with competitive ones. To achieve this objective, iPSCs can be properly differentiated into virtually any cell fate and can be strongly translated into human health via in vitro and in vivo disease modeling for the development of new therapies, the discovery of biomarkers for several disorders, the elaboration and testing of new drugs as novel treatments, and as a tool for personalized medicine.

Human Mesenchymal Stem Cells: The Present Alternative for High-Incidence Diseases, Even SARS-Cov-2.

Mesenchymal stem cells (MSCs), defined as plastic adherent cells with multipotent differentiation capacity in vitro, are an emerging and valuable tool to treat a plethora of diseases due to their therapeutic mechanisms such as their paracrine activity, mitochondrial and organelle transfer, and transfer of therapeutic molecules via exosomes. Nowadays, there are more than a thousand registered clinical trials related to MSC application around the world, highlighting MSC role on difficult-to-treat high-incidence diseases such as the current COVID-19, HIV infections, and autoimmune and metabolic diseases. Here, we summarize a general overview of MSCs and their therapeutic mechanisms; also, we discuss some of the novel clinical trial protocols and their results as well as a comparison between the number of registries, countries, and search portals.

The Systemic Administration of the Histamine H1 Receptor Antagonist/Inverse Agonist Chlorpheniramine to Pregnant Rats Impairs the Development of Nigro-Striatal Dopaminergic Neurons.

The dopaminergic and histaminergic systems are the first to appear during the development of the nervous system. Through the activation of H1 receptors (H1Rs), histamine increases neurogenesis of the cortical deep layers, while reducing the dopaminergic phenotype (cells immunoreactive to tyrosine hydroxylase, TH+) in embryo ventral mesencephalon. Although the function of histamine in neuronal differentiation has been studied, the role of H1Rs in neurogenesis has not been addressed. For this purpose, the H1R antagonist/inverse agonist chlorpheniramine was systemically administered (5 mg/kg, i.p.) to pregnant Wistar rats (gestational days 12-14, E12-14), and control and experimental embryos (E14 and E16) and pups (21-day-old) were evaluated for changes in nigro-striatal development. Western blot and immunohistochemistry determinations showed a significant increase in the dopaminergic markers' TH and PITX3 in embryos from chlorpheniramine-treated rats at E16. Unexpectedly, 21-day-old pups from the chlorpheniramine-treated group, showed a significant reduction in TH immunoreactivity in the substantia nigra pars compacta and dorsal striatum. Furthermore, striatal dopamine content, evoked [3H]-dopamine release and methamphetamine-stimulated motor activity were significantly lower compared to the control group. These results indicate that H1R blockade at E14-E16 favors the differentiation of dopaminergic neurons, but hampers their migration, leading to a decrease in dopaminergic innervation of the striatum in post-natal life.

Establishment of human embryonic stem cell line Amicqui-2 using poor-quality embryos from Mexican population.

Although investigation with human embryonic stem cells (HESC) is not decreasing, the derivation of new lines has been diminished. The preeminence of only a few HESC lines in research is accompanied by lack of universal applicability of results as well as by genetic under-representation. We previously reported the derivation of one line with male karyotype from Mexican population. Here, we derived one HESC line (Amicqui-2) with female karyotype from poor-quality embryos. These line comply the pluripotent requirements (normal karyotype, detection of pluripotency-associated markers, mycoplasma test and teratoma formation) and could be a valuable model for studying diseases specific to under-represented population.

Pluripotency markers in tissue and cultivated cells in vitro of different regions of human amniotic epithelium.

Studies have described the presence of pluripotent markers in vivo and in vitro in human amnion. However, the amnion can be divided into reflected, placental and umbilical regions that are anatomically and functionally heterogeneous. Here, we evaluated the expression of pluripotency markers in tissue and cultivated cells in vitro of different regions of human amnion. To this end, we determined the presence of the core pluripotency factors OCT-4, NANOG and SOX-2 by immunofluorescence and RT-PCR and also performed transcriptome analysis of the different regions of amnion tissue. We identified the mRNA and protein of the pluripotency factors in the different regions of human amnion tissue. However, the OCT-4 and NANOG immunolocalization was cytoplasmic, whereas SOX-2 immunolocalization was nuclear regardless of the region analyzed. Moreover, we found three subpopulations of cells in the in vitro cultures of reflected and placental amnion: cells with immunostaining only in the nucleus, only in the cytoplasm, or in both compartments. Yet no statistically significant differences were found between the reflected and placental amnion. These results suggest a homogeneous distribution of the pluripotency transcription factors of the different regions of human amnion to isolate stem cells that can be used in regenerative medicine.

Maternal Diabetes and Fetal Programming Toward Neurological Diseases: Beyond Neural Tube Defects.

The purpose of this review was to search for experimental or clinical evidence on the effect of hyperglycemia in fetal programming to neurological diseases, excluding evident neural tube defects. The lack of timely diagnosis and the inadequate control of diabetes during pregnancy have been related with postnatal obesity, low intellectual and verbal coefficients, language and motor deficits, attention deficit with hyperactivity, problems in psychosocial development, and an increased predisposition to autism and schizophrenia. It has been proposed that several childhood or adulthood diseases have their origin during fetal development through a phenomenon called fetal programming. However, not all the relationships between the outcomes mentioned above and diabetes during gestation are clear, well-studied, or have been related to fetal programming. To understand this relationship, it is imperative to understand how developmental processes take place in health, in order to understand how the functional cytoarchitecture of the central nervous system takes place; to identify changes prompted by hyperglycemia, and to correlate them with the above postnatal impaired functions. Although changes in the establishment of patterns during central nervous system fetal development are related to a wide variety of neurological pathologies, the mechanism by which several maternal conditions promote fetal alterations that contribute to impaired neural development with postnatal consequences are not clear. Animal models have been extremely useful in studying the effect of maternal pathologies on embryo and fetal development, since obtaining central nervous system tissue in humans with normal appearance during fetal development is an important limitation. This review explores the state of the art on this topic, to help establish the way forward in the study of fetal programming under hyperglycemia and its impact on neurological and psychiatric disorders.

Expresión de microRNAs asociados con corioamnionitis en suero materno / Expression of microRNAs associated with the development of chorioamnionitis in maternal serum

Resumen OBJETIVO Determinar el perfil de expresión de los miRNA-21, -106, -126 y -146 y la cuantificación de IL-1β en el suero de pacientes embarazadas sanas, a término, con y sin trabajo de parto activo y en pacientes con evidencias clínicas de corioamnionitis. MATERIALES Y MÉTODOS Estudio analítico, longitudinal y prolectivo efectuado en pacientes que ingresaron para control, seguimiento obstétrico y terminación del embarazo al Instituto Nacional de Perinatología de la Ciudad de México entre febrero de 2015 y agosto de 2016. Variables de estudio: pacientes embarazadas sanas, a término, con y sin trabajo de parto activo y pacientes con evidencias clínicas de corioamnionitis, edad materna y semanas de gestación. A cada paciente se le tomaron cinco mililitros de sangre periférica para centrifugación y recuperación de suero. La obtención del ARN se efectuó a partir de 500 µL de suero, al que se añadió el mismo volumen del reactivo de TRIzol. El cADN se sintetizó a partir de 3 ng de ARN mediante el ensayo de retrotranscripción. La expresión de los miRNAs se efectuó mediante reacción en cadena de la polimerasa (PCR) con iniciadores específicos. Los resultados se reportan en media ± desviación estándar y el análisis estadístico se llevó a cabo mediante la prueba de Mann-Whitney, con una diferencia significativa de p < 0.05. RESULTADOS Se estudiaron 45 pacientes embarazadas que se dividieron en tres grupos: 1) pacientes sanas a término, sin trabajo de parto activo (n = 15); 2) pacientes con trabajo de parto activo (n = 15); y 3) pacientes con evidencias clínicas de corioamnionitis (n = 15). En las embarazadas sanas, con trabajo de parto activo, el perfil de expresión del miR-126 se incrementó 1.23 veces (p ≤ 0.001) en tanto que el miR-21 y miR-146 disminuyeron 2.1 ( p ≤ 0.001) y 0.73 veces (p ≤ 0.001), respectivamente, y la concentración de IL-1β se incrementó 1.8 veces (p = 0.014) en relación con las pacientes sanas sin trabajo de parto. El perfil de expresión de estos miRNAs y de IL-1β cambió en las pacientes con evidencias clínicas de corioamnionitis. El miR-126 y miR-146 se incrementaron 1.31 (p ≤ 0.001) y 1.1 veces (p = 0.05); en tanto que el miR-21 disminuyó 1.4 veces (p ≤ 0.05) y la concentración de la IL-1β se incrementó 2.8 veces (p = 0.002) con respecto a las pacientes sin trabajo de parto activo. El miR-106 no mostró diferencias significativas entre los tres grupos de estudio. CONCLUSIONES En su conjunto, los resultados de este ensayo sugieren que el perfil de expresión entre miR-21, miR-126 y miR-146 podría considerarse marcador molecular de corioamnionitis. Para que esto pueda tomarse como patrón de referencia deberán emprenderse más ensayos que corroboren este patrón y evalúen su eficacia.

Abstract OBJECTIVE To determine the expression profile of miRNA-21, -106, -126 and -146 and to quantify the secretion of IL-1β in the serum of healthy pregnant patients at term with and without active labor and in patients with clinical evidences of chorioamnionitis. MATERIALS AND METHODS Analytical, longitudinal, and prolective study carried out in patients admitted for control, obstetric, and pregnancy resolution into the National Institute of Perinatology in Mexico City between February 2015 and August 2016. Study variables: healthy pregnant patients at term with and without active labor and patients with clinical evidence of chorioamnionitis, maternal and gestational age. Five milliliters of peripheral blood were taken from each patient, which was centrifuged, and the serum recovered. RNA was obtained from 500 μL of serum to which the same volume of TRIzol reagent was added. The cDNA was synthesized with 3 ng of RNA by the reverse transcription assay. The expression of the microRNAs was performed by polymerase chain reaction (PCR) with specific primers. The results are presented as mean ± standard deviation and statistical analysis was performed using the Mann-Whitney test with a significant difference of p<0.05. RESULTS In healthy pregnant patients with active labor, it was observed that the expression profile of miR-126 increased 1.23-fold (p≤0.001); while the miR-21 and miR-146 decreased 2.1- (pp≤0.001) and 0.73-fold (p≤0.001) respectively and the concentration of IL-1β increased 1.8-fold (p = 0.014) with respect to the healthy patients without labor. The expression profile of these miRNAs and IL-1β change in patients with clinical evidence of chorioamnionitis. The miR-126 and miR-146 increased 1.31- (p≤0.001) and 1.1-fold (p = 0.05); while miR-21 decreased 1.4-fold (p≤0.05) and the concentration of IL-1β increased 2.88-fold (p = 0.002) with respect to patients without active labor. The miR-106 did not show significant differences between the three study groups. CONCLUSIONS These results suggest that miRNA-21, -126 and -146 could be considered as molecular markers in the development of chorioamnionitis; however, more tests should be carried out to corroborate this pattern and evaluate its efficiency.

Capturing the ephemeral human pluripotent state.

During human development, pluripotency is present only in early stages of development. This ephemeral cell potential can be captured in vitro by obtaining pluripotent stem cells (PSC) with self-renewal properties, the human embryonic stem cells (hESC). However, diverse studies suggest the existence of a plethora of human PSC (hPSC) that can be derived from both embryonic and somatic sources, depending on defined culture conditions, their spatial origin, and the genetic engineering used for reprogramming. This review will focus on hPSC, covering the conventional primed hESC, naïve-like hPSC that resemble the ground-state of development, region-selective PSC, and human induced PSC (hiPSC). We will analyze differences and similarities in their differentiation potential as well as in the molecular circuitry of pluripotency. Finally, we describe the need for human feeder cells to derive and maintain hPSC, because they could emulate the interaction of in vivo pluripotent cells with extraembryonic structures that support development. Developmental Dynamics 245:762-773, 2016. © 2016 Wiley Periodicals, Inc.