Mouse PUMILIO1 (PUM1) and PUMILIO2 (PUM2) belong to the PUF (Pumilio/FBF) family, a highly conserved RNA binding protein family whose homologues play critical roles in embryonic development and germ line stem cell maintenance in invertebrates. However, their roles in mammalian embryonic development and stem cell maintenance remained largely uncharacterized. Here we report an essential requirement of the Pum gene family in early embryonic development. A loss of both Pum1 and Pum2 genes led to gastrulation failure, resulting in embryo lethality at E8.5. Pum-deficient blastocysts, however, appeared morphologically normal, from which embryonic stem cells (ESCs) could be established. Both mutant ESCs and embryos exhibited reduced growth and increased expression of endoderm markers Gata6 and Lama1, making defects in growth and differentiation the likely causes of gastrulation failure. Furthermore, ESC Gata6 transcripts could be pulled down via PUM1 immunoprecipitation and mutation of conserved PUM-binding element on 3′UTR (untranslated region) of Gata6 enhanced the expression of luciferase reporter, implicating PUM-mediated posttranscriptional regulation of Gata6 expression in stem cell development and cell lineage determination. Hence, like its invertebrate homologues, mouse PUM proteins are conserved posttranscriptional regulators essential for embryonic and stem cell development.
Interleukin-17 (IL-17) is known as a Th17-cell-derived proinflammatory cytokine, which plays a pivotal role in several inflammatory and autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and psoriasis. Emerging evidence has shown that IL-17 is linked to endometriosis, although the etiology of endometriosis is still unknown. The IL-17 expression is up-regulated in serum, peritoneal fluid (PF) and endometriotic lesions from patients with endometriosis but the related regulation mechanisms are complex and obscure. Meanwhile, the specific roles of IL-17 in endometriosis are also worthy of further exploration. Through the integration and summary of literature, we conclude that the secretion of IL-17 increases under the regulation of ectopic microenvironment and other factors, and then IL-17 is deeply involved in endometriosis in the regulation of immune microenvironment, the invasion and growth of ectopic lesions, and so on, which implies its therapeutic value in this disorder.
C-C motif ligand 2 (CCL2), also known as monocytic chemotactic protein 1 (MCP-1), is an integral chemotactic factor which recruits macrophages for the immune response. Together with its receptors (e.g., CCR2, ACKR1, and ACKR2), they exert noticeable influences on various diseases of different systems. At the maternal-fetal interface, CCL2 is detected to be expressed in trophoblasts, decidual tissue, the myometrium, and others. Meanwhile, existing reports have determined a series of physiological regulators of CCL2, which functions in maintaining normal recruitment of immunocytes, tissue remodeling, and angiogenesis. However, abnormal levels of CCL2 have also been reported to be associated with adverse pregnancy outcomes such as spontaneous abortion, preeclampsia and preterm labor. In this review, we concentrate on CCL2 expression at the maternal-fetal interface, as well as its precise regulatory mechanisms and classic signaling pathways, to reveal the multidimensional aspects of CCL2 in pregnancy.
Problem Decidual stromal cells (DSCs) are important origins of cytokines to modulate maternal‐fetal immunotolerance and provide a feasible environment for embryo implantation and development. Interleukin (IL)‐24 is a multifunctional cancer killing cytokine and a pleiotropic immunoregulator with complex potency according to tissue or cell types. Its role in establishment and maintenance of normal pregnancy is largely unknown. The aim of our study was to investigate the function and significance of IL‐24 and its receptor in the coordination between DSCs and natural killer cells (NK) in early pregnancy. Method of study The levels of IL‐24 in DSC, endometrial stromal cell (ESC), peripheral blood NK cells (pNK), or decidual NK cells (dNK) culture supernatants were detected by enzyme‐linked immunosorbent assay (ELISA), and the levels of IL‐24 receptors were determined by real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) and flow cytometry assays. The effect of IL‐24 on the functions of decidual NK cells was analyzed by flow cytometry assays in vitro. Results The concentration of IL‐24 in culture supernatant of DSCs was significantly higher than that of ESCs. Both eNK (endometrial NK cells) and dNK highly expressed IL‐24 receptors (IL‐20R1 and IL‐22R1), especially on CD56dim eNK. However, there were extremely low levels of IL‐20R1 and IL‐22R1 on pNK. Recombinant human IL‐24 or DSCs‐secreted IL‐24 downregulated the levels of CD16, Granzyme B, perforin, and interferon (IFN)‐γ and upregulated the levels of inhibitory receptors killer‐cell immunoglobulin‐like receptor (KIR)2DL1 and KIR3DL1, or immunotolerant or angiogenic cytokines (eg, transforming growth factor (TGF)‐β, IL‐10, and IL‐8), and elevated the percentage of CD56brightCD16−dNK in vitro. Conclusion These data suggest that DSCs promote the differentiation of CD56brightCD16−NK with high levels of inhibitory receptors, immunotolerant, and angiogenic cytokines by secreting IL‐24 during decidualization in early pregnancy.
Summary Wooden breast myopathy affects the quality of fresh and processed chicken breast muscle. The objective of this study was to construct a classification method by instrumental stress, and the effects of wooden breast myopathy on meat quality and oral processing property, and was to explore correlations between stress and oral processing parameters. The severity of wooden breast myopathy was highly correlated to fillet weight (R2 = 0.740), thickness (R2 = 0.826) and hardness (R2 = 0.803) (P < 0.01). The 3D scatter model based on stress is robust and reliable to classify the fillets into four categories (normal, mild, moderate and severe wooden breast fillets), avoiding manual grading. Moisture, fat, collagen, pH, drip loss, cooking loss, thawing loss, purge loss, hardness, gumminess and chewiness significantly increased with the severity of wooden breast myopathy, whereas fat, ash and water/salt‐soluble protein contents significantly decreased (P < 0.05). Shear force reached the maximum (36.32 N) when this myopathy was moderate. The myopathy led to an increase in masseter activity and the particle size of the bolus. Significantly higher correlations between stress, Dx(50) (R2 = 0.790), Dx(90) (R2 = 0.771) and D[4,3] (R2 = 0.797) were found (P < 0.01). This study also showed that jaw movement and muscle activity could be used to understand the links between physical property and orally sensory property.
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