Intrauterine adhesion (IUA) is a major cause of female secondary infertility. We previously demonstrated that menstrual blood-derived stromal cell (MenSC) transplantation helped severe IUA patients ...have pregnancy and endometrium regeneration. We also initiated platelet-rich plasma (PRP) acted as a beneficial supplement in MenSC culturing and a potential endometrial receptivity regulator. Here, we investigated the therapeutic effect of combined transplantation of MenSCs with PRP in rat IUA models and the mechanisms of MenSCs in endometrium regeneration.
Rat IUA models were established by intrauterine mechanical injured. Nine days later, all rats were randomly assigned to four groups received different treatment: placebo, MenSC transplantation, PRP transplantation, and MenSCs + PRP transplantation. The traces of MenSCs were tracked with GFP label. Endometrial morphology and pathology, tissue proliferation, inflammation, pregnancy outcomes, and mechanism of MenSCs in the regeneration of endometrium were investigated.
Notably, at days 9 and 18 post-treatment, MenSC transplantation significantly improved endometrial proliferation, angiogenesis, and morphology recovery and decreased collagen fibrosis and inflammation in the uterus. MenSCs had lesion chemotaxis, colonized around the endometrial glands. Gene expression of human-derived secretory protein IGF-1, SDF-1, and TSP-1 was detected in the uterus received MenSCs at day 18. The three treatments can all improve fertility in IUA rats. Moreover, gene expressions of cell proliferation, developmental processes, and other biological processes were induced in MenSC transplantation group. Hippo signaling pathway was the most significantly changed pathway, and the downstream factors CTGF, Wnt5a, and Gdf5 were significantly regulated in treatment groups. PRP enhanced these parameters through a synergistic effect.
In summary, MenSCs could effectively improve uterine proliferation, markedly accelerate endometrial damage repairment and promote fertility restoration in IUA rats, suggesting a paracrine restorative effect and Hippo signaling pathway stimulation. Our results indicate MenSCs, a valuable source of cells for transplantation in the treatment intrauterine adhesion. Combined with PRP, this cell therapy was more effective.
Secondary structure plays an important role in determining the function of noncoding RNAs. Hence, identifying RNA secondary structures is of great value to research. Computational prediction is a ...mainstream approach for predicting RNA secondary structure. Unfortunately, even though new methods have been proposed over the past 40 years, the performance of computational prediction methods has stagnated in the last decade. Recently, with the increasing availability of RNA structure data, new methods based on machine learning (ML) technologies, especially deep learning, have alleviated the issue. In this review, we provide a comprehensive overview of RNA secondary structure prediction methods based on ML technologies and a tabularized summary of the most important methods in this field. The current pending challenges in the field of RNA secondary structure prediction and future trends are also discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metallic elements play a pivotal role in maternal and fetal health. Metals can cross the placental barrier and be absorbed by fetuses, where they may affect closure of the neural tube during ...embryonic development. Neural tube defects (NTDs), which result from aberrant closure of the neural tube three to four weeks post-conception, have a multifactorial and complex etiology that combines genetic variants and environmental exposure. Recent advances in population-level association studies have investigated the link between maternal environmental exposure and NTDs, particularly the influence of metals on the incidence of NTDs. Herein, we present a broad and qualitative review of current literature on the association between maternal and prenatal metal exposure via the maternal peripheral blood, amniotic fluid, placenta, umbilical cord, and maternal hair, and the risk of developing NTDs. Specifically, we identify the various aggravating or attenuating effects of metallic exposure on the risk of NTD formation. This review provides novel insights into the association between environmental metals and NTDs and has important applications for NTD prevention and mitigating environmental exposure to metals.
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•Environmental metals impact fetus health and lead to adverse pregnancy outcomes.•Exposure to toxic heavy metals is linked to an elevated risk of NTDs.•Low/high levels of zinc and molybdenum in the blood/placenta is linked to NTDs.•Cobalt exhibits a protective effect against NTDs by producing cobalamin.•Future work should analyze metal exposure in samples from the early trimester.
Impaired autophagy and excessive apoptosis disrupt cellular homeostasis and contribute to neural tube defects (NTDs), which are a group of fatal and disabling birth defects caused by the failure of ...neural tube closure during early embryonic development. However, the regulatory mechanisms underlying NTDs and outcomes remain elusive. Here, we report the role of the transcription factor nuclear factor I-C (NFIC) in maintaining cellular homeostasis in NTDs. We demonstrated that abnormally elevated levels of NFIC in a mouse model of NTDs can interact with the miR-200b promoter, leading to the activation of the transcription of miR-200b, which plays a critical role in NTD formation, as reported in our previous study. Furthermore, miR-200b represses autophagy and triggers apoptosis by directly targeting the autophagy-related gene Ambra1 (Autophagy/Beclin1 regulator 1). Notably, miR-200b inhibitors mitigate the unexpected effects of NFIC on autophagy and apoptosis. Collectively, these results indicate that the NFIC-miR-200b-Ambra1 axis, which integrates transcription- and epigenome-regulated miRNAs and an autophagy regulator, disrupts cellular homeostasis during the closure of the neural tube, and may provide new insight into NTD pathogenesis.
Objective:
Cleft lip and palate (CLP) is the most common human cranial and maxillofacial birth defect. The aim of this bibliometric analysis was to provide an overview of the development of ...CLP-related research.
Method:
Cleft lip and palate-related studies published from 2000 to 2017 were retrieved from the Science Citation Index Expanded core database. Publication date, journal, authors, first authors, keywords, and citations were extracted and quantitatively analyzed using Bibliographic Item Co-Occurrence Matrix Builder software. The word matrix and co-occurrence matrix were established, and the co-citation analysis, keyword clustering, and social network analysis (SNA) of highly cited papers were completed.
Results:
A total of 9040 articles were retrieved from the 18 years of publications that were searched. The number of documents steadily increased over the period of interest, with a slight decrease in 2016 and 2017. This article separately examined the top most cited papers and high-frequency keywords from 3 time periods: 2000 to 2005, 2006 to 2011, and 2011 to 2017. The strategy coordinates of citation reflect TGF-β3, MSX1 gene, technique for cleft lip repair, TTF2, P63, IRF6 gene, FGF signaling, PVRL1, TGFBR2, and BMP4 gene as areas of research interest in the field. Moreover, the SNA of keywords highlighted new research topics: meta-analysis, cone beam computed tomography, tooth agenesis, case–control study, association study, micrognathia, DiGeorge syndrome, NSCL/P, UCLP, GWAS, MTHFR, and CLPTM1L.
Conclusion:
We conducted bibliometric research of CLP across an 18-year span. The results help to define an overall command of the latest topics in CLP and provide insight for launching new projects.
We previously reported that transplantation of menstrual blood-derived stromal cells (MenSCs) significantly improved fertility restoration in intrauterine adhesion (IUA). However, it is difficult to ...obtain menstrual blood samples in some severe IUA patients who have amenorrhea or oligomenorrhea. Thus, a safe and effective stem cell replacement therapy is necessary to promote endometrial regeneration. Recent studies demonstrated that the effects of MenSCs are partly mediated in a paracrine manner
via
small extracellular vesicles (sEVs). To explore this possibility, we performed a pre-clinical study to investigate whether concentrated MenSC-derived sEVs (MenSCs-sEVs) are sufficient to repair IUA and the mechanisms underlying their action. Rat IUA models were established by mechanical injury, followed by the administration of MenSCs or MenSCs-sEVs through intrauterine transplantation. Consistent with the efficacy of MenSCs, MenSCs-sEVs effectively recovered the morphology, promoted regeneration of the glands and angiogenesis, and reversed endometrial fibrosis in the IUA uterus. The endometrial receptivity and pregnancy outcome significantly improved after repeated MenSCs-sEVs transplantations. In addition, all rats in the MenSCs-sEVs group had no hematological or biochemical abnormalities. Three-dimensional fluorescence imaging suggested that MenSCs tended to migrate through the bloodstream, whereas MenSCs-sEVs had a better localized therapeutic effect. Moreover, MenSCs and MenSCs-sEVs inhibited the TGFβ1/SMAD3 pathway in the IUA endometrium, while promoting the phosphorylation of SMAD1/5/8 and ERK 1/2 and upregulating the expression of BMP7. Thus, MenSCs-sEVs safely and effectively enhanced endometrial restoration, suggesting a promising non-cellular therapy for endometrial regeneration and a key role in MenSC-mediated IUA treatment.
MenSCs-sEVs safely and effectively enhanced endometrial restoration, suggesting a promising non-cellular therapy for endometrial regeneration and a key role in MenSC-mediated IUA treatment.
Spina bifida aperta is a type of neural tube defect (NTD). Although prenatal fetal surgery has been an available and effective treatment for it, the neurological functional recovery is still need to ...be enhanced. Our previous results revealed that deficiencies of sensory, motor, and parasympathetic neurons were primary anomalies that occurred with the spinal malformation. Therefore, we emphasized that nerve regeneration is critical for NTD therapy. We delivered an adenoviral construct containing genes inserted for green fluorescent protein and brain-derived neurotrophic factor (Ad-GFP-BDNF) into the amniotic fluid to investigate its prenatal therapeutic potential for rat fetuses with spina bifida aperta. Using immunofluorescence, TdT-mediated dUTP nick-end labeling staining, and real-time polymerase chain reaction analysis, we assessed cell apoptosis in the defective spinal cord and Brn3a positive neuron survival in the dorsal root ganglion (DRG); a protein array was used to investigate the microenvironmental changes of the amniotic fluid. We found that most of the overexpressed BDNF was present on the lesions of the spina bifida fetuses, the number of apoptosis cells in Ad-GFP-BDNF-transfected spinal cords were reduced, mRNA levels of Bcl2/Bax were upregulated and Casp3 were downregulated compared with the controls, the proportion of Brn3a positive neurons in DRG were increased by activating the BDNF/TrkB/Akt signaling pathway, and most of the significant changes in cytokines in the amniotic fluid were related to the biological processes of regulation of apoptotic process and generation of neurons. These results suggest that intra-amniotic Ad-GFP-BDNF gene delivery might have potential as a supplementary approach to treat congenital malformations of neural tubes.
Premature ovarian insufficiency (POI) is one of the major causes of infertility. We previously demonstrated that transplantation of menstrual blood-derived stromal cells (MenSCs) effectively improved ...ovarian function in a murine model of POI. Recent studies indicated that mesenchymal stem cell-derived exosomes were important components in tissue repair. In this study, we investigated the therapeutic effects of MenSCs-derived exosomes (MenSCs-Exos) in a rat model of POI and its mechanism in restoring ovulation.
Ovaries of 4.5-day-old Sprague Dawley rats (SD rats) were cultured in vitro to evaluate the effects of MenSCs-Exos exposure on early follicle development. Furthermore, POI in rats was induced by intraperitoneal administration of 4-vinylcyclohexene diepoxide (VCD). Forty-eight POI rats were randomly assigned to four groups, each receiving a different treatment: PBS, MenSCs, MenSCs-Exos, and Exo-free culture supernatant of MenSCs. Estrous cyclicity, ovarian morphology, follicle dynamics, serum hormones, pregnancy outcomes, and molecular changes were investigated.
Exposure to MenSCs-Exos promoted the proliferation of granulosa cells in primordial and primary follicles in vitro and increased the expression of early follicle markers Deleted In Azoospermia Like (DAZL) and Forkhead Box L2 (FOXL2) while inhibiting follicle apoptosis. In vivo, MenSCs-Exos transplantation effectively promoted follicle development in the rat model of POI and restored the estrous cyclicity and serum sex hormone levels, followed by improving the live birth outcome. In addition, transplantation of MenSCs-Exos regulated the composition of the ovarian extracellular matrix and accelerated the recruitment of dormant follicles in the ovarian cortex and increased proliferation of granulosa cells in these follicles.
MenSCs-Exos markedly promoted follicle development in vitro and in vivo and restored fertility in POI rats, suggesting a restorative effect on ovarian functions. The therapeutic effect of MenSCs-Exos transplantation was sustainable, consistent with that of MenSCs transplantation. Our results suggested that MenSCs-Exos transplantation may be a promising cell-free bioresource in the treatment of POI.
There are limited studies on the associations between prenatal exposure to constituents of fine particulate matter (PM2.5) and children’s intelligence quotient (IQ). Our study aimed to explore the ...associations between prenatal PM2.5 and its six constituents and the IQ levels of 6-year-old children. We included 512 mother-child pairs. We used a satellite-based modelling framework to estimate prenatal PM2.5 and its six constituents (ammonium, sulfate, nitrate, organic carbon, soil dust, and black carbon). We assessed the children’s IQ using the short form of the Wechsler Intelligence Scale. Perceptual Reasoning Index (PRI), Verbal Comprehension Index (VCI), and Full Scale IQ (FSIQ) scores were computed. The multiple informant model (MIM) was applied to explore the trimester specific effects of PM2.5 and its six constituents’ exposure on children’s PRI, VCI, and FSIQ. To examine whether the duration of breastfeeding and physical activity (PA) could modify the effects of PM2.5 on children’s IQ, we stratified the analyses according to the duration of breastfeeding (≤6 and >6 months) and time of outdoor activities after school (≤2 and >2 h/week). The first trimester PM2.5 and its five constituents’ exposures were inversely associated with FSIQ β = −1.34, 95 % confidence interval CI (−2.71, 0.04) for PM2.5 and PRI β = −2.18, 95 %CI (−3.80, −0.57) for PM2.5 in children. The associations were magnified among boys and those with less outdoor activities or shorter breastfeeding duration. Our results indicate that prenatal PM2.5 and several of its main constituents’ exposure may disrupt cognitive development in children aged 6 years. More PA and longer breastfeeding duration may alleviate the detrimental effects of prenatal PM2.5 exposure on children’s cognitive function.
•PM2.5 and its constituents exposure during 1st trimester decreased children’s IQ•The adverse effects were more pronounced among boys•More PA and longer breastfeeding duration may alleviate the detrimental effects•Prenatal PM2.5 exposure may disrupt cognitive development in 6-year-old children
Since the discovery of the nuclear factor kappa B (NF-ĸB) transcription factor 36 years ago, many studies have linked the NF-ĸB signaling pathway to pathological and physiological processes, such as ...inflammation, immune response, and tumorigenesis. However, as the NF-ĸB signaling pathway is evolutionarily conserved from flies to humans, an increasing number of studies have focused on the impact of NF-ĸB signaling on developmental processes. While our understanding of the mechanisms underlying NF-ĸB signaling involved in tissue and organ development is limited, the numerous studies conducted in recent years have provided preliminary insights into these molecular mechanisms. In this review, we summarize the latest information on the molecular mechanisms behind NF-ĸB signaling involved in tissue and organ development, highlighting the role and significance of the NF-ĸB signaling pathway in developmental processes. This review elucidates the fact that the development of nearly all tissues is associated with NF-ĸB signaling, either directly or indirectly.
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•NF-ĸB signaling associated with nearly all systems during embryogenesis.•RelA in canonical NF-ĸB signaling strongly implicated in developmental processes.•Moderate NF-ĸB signaling expression vital to embryonic development.•NF-ĸB signaling pathway usually synergistic with other developmental pathways.•NF-ĸB signaling a potential therapeutic target for dysplastic diseases.
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