Association between Insulin-Like Growth Factor-1 and Relative Skeletal Maturation: A Retrospective Cohort Study of Short Children and Adolescents

Objective. Delays in skeletal maturity are related to bone mass and fracture risk in children, but the factors that determine it are unknown. We aimed to identify the association between insulin-like growth factor-1 (IGF-1) and skeletal maturation before and after growth hormone (GH) treatment. Methods. In this retrospective cohort study, we observed 783 short children and adolescents, 229 of whom received GH therapy. Skeletal maturation was assessed based on the difference between bone age (BA) and chronological age (CA) (noted as BA-CA). Anthropometric data and laboratory values were measured, and BA was evaluated using the Greulich and Pyle method. Results. The delayed BA group was defined as BA‐CA<−2 SD (n=457), and the occurrence rate of BA delay was 58.37%. A nonlinear relationship was observed between the IGF-1 standard deviation score (IGF-1 SDS) and BA-CA before and after GH therapy. Before GH therapy, there was a significant positive association between the IGF-1 SDS and BA-CA when the IGF-1 level was greater than -2 SDS (β 0.17, 95% CI 0.08, 027; P<0.001). However, we did not observe a significant relationship between the IGF-1 SDS and BA-CA when the IGF-1 level was lower than -2 SDS (β 0.07, 95% CI -0.12, 0.26; P=0.454). After GH therapy, there was a significant positive association between the IGF-1 SDS and BA-CA when the IGF-1 level was lower than 2 SDS (β 0.20, 95% CI 0.12, 028; P<0.001). However, we did not observe a significant relationship between the IGF-1 SDS and BA-CA when the IGF-1 level was greater than 2 SDS (β -0.03, 95% CI -0.33, 0.27; P=0.866). Conclusion. BA is more delayed in short children and adolescents. There is a nonlinear relationship between IGF-1 and BA maturation in short children before and after GH treatment. These findings suggest that a low level of IGF-1 may contribute to BA delay in short children and adolescents

Circular RNAs are abundantly expressed and upregulated during repair of the damaged endometrium by Wharton’s jelly-derived mesenchymal stem cells

Abstract Background Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) exhibit strong and powerful potential in repairing different diseases. The expression profile of circular RNA (circRNA) provides valuable insight for regulation of the repair process and exploration of reparative effect mechanisms. Methods Human endometrial stromal cells (ESCs) were cultured with mifepristone to obtain damaged ESCs, which were then cocultured with or without WJ-MSCs (cocultured group versus non-cocultured group) to observe the reparative effect upon damaged ESCs by WJ-MSCs. CircRNA microarray was performed between the two groups. Based on the transcriptomics data, the differential gene expression profiles of the two groups were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and network analysis methods. Screening of a circRNA database was performed, and the results were confirmed by quantitative polymerase chain reaction (qPCR). Results WJ-MSCs exerted a reparative effect upon damaged ESCs in the cocultured group such as improved cell morphology, higher proliferative ability, and lower apoptosis rate. CircRNA array showed that 7757 circRNAs were differentially expressed in ESCs from the cocultured group. Mitotic cell cycle, cell cycle process, and nuclear division ranked top in the GO upregulated list of the two groups, while DNA replication and cell cycle ranked top in the KEGG pathway analysis upregulated list of the two groups. The nine most aberrantly expressed circRNAs were selected for further verification in the same cohort of samples by microarray analysis. Seven of the nine most aberrantly circRNAs were confirmed to be significantly upregulated in the cocultured group. And four of the seven circRNAs (hsa_circ_0015825, hsa-circRNA4049-38, hsa-circRNA5028-15, and hsa_circ_0111659) expression both in ESCs and WJ-MSCs tended to decrease with time by qPCR. The levels of the remaining three circRNAs (hsa-circRNA8881-21, hsa_circ_0020492 and hsa_circ_ 0026141) did not change significantly over time in either ESCs or WJ-MSCs. Moreover, we focused on hsa_circRNA_0111659 and predicted its miRNAs and targeted mRNA. The association of circRNA-miRNA-mRNA is likely to be involved in regulating the repair of endometrial damage. Conclusions Our results presented the abundant and upregulated circRNAs profile during repair of the damaged endometrium by WJ-MSCs and provided a novel perspective for circRNAs in the regulation of WJ-MSCs for endometrial repair

Differentiation of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells into endometrial cells

Abstract Background Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are a novel and promising strategy for tissue engineering because of their ability to differentiate into many cell types. We characterized the differentiation of WJ-MSCs into endometrial epithelial cell (EEC)-like and endometrial stromal cell (ESC)-like cells and assessed the effect of 17β-estradiol and 8-Br-cAMP on the differentiation system. Methods WJ-MSCs were treated in two ways to differentiate into EEC-like and ESC-like cells respectively: cocultured with ESCs in control/differentiation medium (17β-estradiol, growth factors); and cultured in control/differentiation medium (8-Br-cAMP alone or 8-Br-cAMP plus 17β-estrogen and growth factors). Three signaling pathway inhibitors (SB203580, PD98059, H89) were used to investigate the mechanism of WJ-MSC differentiation into ESC-like cells. Immunofluorescence, western blot and flow cytometry analyses were used to analyze expression of epithelial markers and stromal cell markers. Enzyme-linked immunosorbent assays were used to test the production of secretory proteins associated with the differentiation of ESC-like cells. Results 17β-estradiol at 1 μM downregulated vimentin and CD13 and upregulated cytokeratin and CD9 proteins, promoting the differentiation of WJ-MSCs into EEC-like cells in the coculture system. 8-Br-cAMP at 0.5 mM upregulated vimentin and CD13 and downregulated CK and CD9, promoting the differentiation of WJ-MSCs into ESC-like cells. Prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) were upregulated and the protein kinase A (PKA) signaling pathway was activated, whereas extracellular signal-regulated (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were not affected. Conclusions 17β-estradiol at 1 μM is a good inducer for facilitating the differentiation of WJ-MSCs into EEC-like cells. 8-Br-cAMP plus estrogen and growth factors can induce the differentiation of WJ-MSCs into ESC-like cells. During the differentiation of WJ-MSCs into ESC-like cells, PRL and IGFBP1 were upregulated by the treatment and the PKA signaling pathway was activated, whereas ERK1/2 and p38 MAPK were not affected. These findings suggest a promising approach to the treatment of endometrial damage and other endometrial diseases and suggest new applications for WJ-MSCs in clinical practice

Residual chlorine disrupts the microbial communities and spreads antibiotic resistance in freshwater

Chlorine disinfection is a key global public health strategy for the prevention and control of diseases, such as COVID-19. However, little is known about effects of low levels of residual chlorine on freshwater microbial communities and antibiotic resistomes. Here, we treated freshwater microcosms with continuous low concentrations of chlorine and quantified the effects on aquatic and zebrafish intestinal microbial communities and antibiotic resistomes, using shotgun metagenome and 16S rRNA gene sequencing. Although chlorine rapidly degraded, it altered the aquatic microbial community composition over time and disrupted interactions among microbes, leading to decreases in community complexity and stability. However, community diversity was unaffected. The majority of ecological functions, particularly metabolic capacities, recovered after treatment with chlorine for 14 d, due to microbial community redundancy. There were also increased levels of antibiotic-resistance gene dissemination by horizontal and vertical gene transfer under chlorine treatment. Although the zebrafish intestinal microbial community recovered from temporary dysbiosis, growth and behavior of zebrafish adults were negatively affected by chlorine. Overall, our findings demonstrate the negative effects of residual chlorine on freshwater ecosystems and highlight a possible long-term risk to public health.This study was financially supported by the consulting research project of Chinese Academy of Engineering (2020-ZD-15), National Natural Science Foundation of China (21777144, 21976161, and 41907210), and Program for Changjiang Scholars and Innovative Research Team in University (IRT_17R97).Peer reviewe

Native T1 Mapping and Magnetization Transfer Imaging in Grading Bowel Fibrosis in Crohn’s Disease: A Comparative Animal Study

In this study, we investigated the utility of native T1 mapping in differentiating between various grades of fibrosis and compared its diagnostic accuracy to magnetization transfer imaging (MTI) in a rat model of CD. Bowel specimens (64) from 46 CD model rats undergoing native T1 mapping and MTI were enrolled. The longitudinal relaxation time (T1 value) and normalized magnetization transfer ratio (MTR) were compared between none-to-mild and moderate-to-severe fibrotic bowel walls confirmed by pathological assessments. The results showed that the correlation between the T1 value and fibrosis (r = 0.438, p &lt; 0.001) was lower than that between the normalized MTR and fibrosis (r = 0.623, p &lt; 0.001). Overall, the T1 values (t = −3.066, p = 0.004) and normalized MTRs (z = 0.081, p &lt; 0.001) in none-to-mild fibrotic bowel walls were lower than those in moderate-to-severe fibrotic bowel walls. The area under the curve (AUC) of the T1 value (AUC = 0.716, p = 0.004) was significantly lower than that of the normalized MTR (AUC = 0.881, p &lt; 0.001) in differentiating moderate-to-severe fibrosis from none-to-mild fibrosis (z = −2.037, p = 0.042). Our results support the view that the T1 value could be a promising imaging biomarker in grading the fibrosis severity of CD. However, the diagnostic performance of native T1 mapping was not superior to MTI

Development of a machine-learning model to identify the impacts of pesticides characteristics on soil microbial communities from high-throughput sequencing data.

High-throughput sequencing (HTS) of soil environmental DNA provides an advanced insight into the effects of pesticides on soil microbial systems. However, the association between the properties of the pesticide and its ecological impact remains methodically challenging. Risks associated with pesticide use can be minimized if pesticides with optimal structural traits were applied. For this purpose, we merged the 20 independent HTS studies, to reveal that pesticides significantly reduced beneficial bacteria associated with soil and plant immunity, enhanced the human pathogen and weaken the soil's ecological stability. Through the machine-learning approach, correlating these impacts with the physicochemical properties of the pesticides yielded a random forest model with good predictive capabilities. The models revealed that physical pesticide properties such as the dissociation constant (pKa), the molecular weight and water solubility, determined the ecological impact of pesticides to a large extent. Moreover, this study identified that eco-friendly pesticides should possess a value of pKa > 5 and a molecular weight in the range of 200–300 g/mol, which were found to be conducive to bacteria related to plant immunity promotion and exerted the lowest fluctuation of human opportunistic pathogen and keystone species. This guides the design of pesticides for which the impacts on soil biota are minimized.Environmental Biolog

Additional file 1: Figure S1. of Differentiation of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells into endometrial cells

showing identification of WJ-MSCs. (A) Observation of WJ-MSCs under a phase-contrast microscope. (a) Seven days after the tissues of Wharton’s jelly were plated, many triangular and spindle-shaped cells dissociated from the tissues. (b) About half a month later, these adherent cells were able to reach 80% confluence. (c) Third-generation cells exhibited a spindle shape and upon reaching confluence formed a whirlpool-like pattern. Bar represents 200 μm. (B) Surface antigens of WJ-MSCs in flow cytometry. WJ-MSCs were positive for CD90 and CD105; WJ-MSCs were negative for CD14, CD34, CD45, CD79a, and HLA-DR. Results confirmed that cells were MSCs but nonhematopoietic. (C) Differentiation potential of WJ-MSCs toward osteogenic and adipogenic lineages. Osteogenic differentiation assayed using the von Kossa procedure and adipogenic differentiation determined by formation of lipid vacuoles after induction. (a) No mineralized matrix formation found in WJ-MSCs cultured in regular growth medium. (b) Osteogenic differentiation determined by staining with Alizarin red after osteogeneic induction. (c) No lipid vacuoles found in WJ-MSCs cultured in regular medium. (d) Adipogenic differentiation detected by Oil red O staining. Bar represents 400 μ

Additional file 2: Figure S2. of Differentiation of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells into endometrial cells

showing identification of ESCs and EECs. (A) Morphological characteristics of ESCs. Bar represents 200 μm. (B) Morphological characteristics of EECs. Bar represents 200 μm. (C) Observation of ESCs after immunofluorescent staining. Results show ESCs in primary culture positively stained by vimentin and CD13 but negatively stained for cytokeratin and CD9. (a), (e) Nuclear counterstaining with Hoechst 33342. (b) ESCs positively stained by vimentin. (c) ESCs positively stained by CD13. (d) Merger of (a)–(c). (f) ESCs negatively stained by cytokeratin. (g) ESCs negatively stained by CD9. (h) Merger of (e)–(g). Bar represents 200 μm. (D) Observation of EECs after immunofluorescent staining. Results show that EECs in primary culture were positively stained by cytokeratin and CD9 but negatively stained for vimentin and CD13. (a), (e) Nucleal counterstaining with Hoechst 33342. (b) EECs negatively stained by vimentin. (c) EECs negatively stained by CD13. (d) Merger of (a)–(c). (f) EECs positively stained by cytokeratin. (g) ESCs positively stained by CD9. (h) Merger of (e)–(g). Bar represents 200 μm (TIFF 31403 kb