Bin Ni

Background: Kidney organoids derived from human pluripotent stem cells (HiPSCs) hold huge applications for drug screening, disease modeling, and cell transplanting therapy. However, these applications are limited since kidney organoid cannot maintain complete morphology and function like human kidney. Kidney organoids are not well differentiated since the core of the organoid lacked oxygen, nutrition, and vasculature, which creates essential niches. Hypoxia-inducible factor-1 α (HIF-1α) serves as a critical regulator in vascularization and cell survival under hypoxia environment. Less is known about the role of HIF-1α in kidney organoids in this regard. This study tried to investigate the effect of HIF-1α in kidney organoid vascularization and related disease modeling. Methods: For the vascularization study, kidney organoids were generated from human induced pluripotent stem cells. We overexpressed HIF-1α via plasmid transfection or treated DMOG (Dimethyloxallyl Glycine, an agent for HIF-1α stabilization and accumulation) in kidney progenitor cells to detect the endothelium. For the disease modeling study, we treated kidney organoid with cisplatin under hypoxia environment, with additional HIF-1α transfection. Result: HIF-1α overexpression elicited kidney organoid vascularization. The endothelial cells and angiotool analysis parameters were increased in HIF-1α plasmid-transfected and DMOG-treated organoids. These angiogenesis processes were partially blocked by VEGFR inhibitors, semaxanib or axitinib. Cisplatin-induced kidney injury (Cleaved caspase 3) was protected by HIF-1α through the upregulation of CD31 and SOD2. Conclusion: We demonstrated that HIF-1α elicited the process of kidney organoid vascularization and protected against cisplatin-induced kidney organoid injury in hypoxia environment.

A growing body of studies have investigated the association between air pollution exposure during early pregnancy and the risk of orofacial clefts, but these studies put more emphasis on particulate matter and reported inconsistent results, while research on the independent effects of gaseous air pollutants on orofacial clefts has been quite inadequate, especially in China. A case–control study was conducted in Changsha, China from 2015 to 2018. A total of 446 cases and 4460 controls were included in the study. Daily concentrations of CO, NO₂, SO₂, O₃, PM_2.5 and PM₁₀ during the first trimester of pregnancy were assigned to each subject using the nearest monitoring station method. Multivariate logistic regression models were applied to evaluate the associations of monthly average exposure to gaseous air pollutants with orofacial clefts and its subtypes before and after adjusting for particulate matter. Variance inflation factors (VIFs) were used to determine if the effects of gaseous air pollutants could be independent of particulate matter. Increase in CO, NO₂ and SO₂ significantly increased the risk of cleft lip with or without cleft palate (CL/P) in all months during the first trimester of pregnancy, with aORs ranging from 1.39 to 1.48, from 1.35 to 1.61 and from 1.22 to 1.35, respectively. The risk of cleft palate only (CPO) increased with increasing NO₂ exposure levels in the first trimester of pregnancy, with aORs ranging from 1.60 to 1.66. These effects sustained and even exacerbated after adjusting for particulate matter. No significant effect of O₃ was observed. Our study suggested that maternal exposure to CO, NO₂, and SO₂ during the first trimester of pregnancy might contribute to the development of orofacial clefts, and the associations were potentially independent of particulate matter.

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease common among infants and children. It is associated with a high risk of allergies, asthma, and mental health problems. Attempts have been made to use probiotics in clinical interventions for AD. Objective Our objective was to perform an updated meta-analysis of recently published studies to evaluate the effect of probiotics in the prevention and treatment of AD in children and to further understand the role of probiotics in AD interventions in the clinic. Method We searched the PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang databases with prespecified selection criteria from inception of each database to 11 January 2020. No language restrictions were applied. Results A total of 25 studies were included in our meta-analysis. Of these, 14 were prevention studies (with 3049 children enrolled) and 11 were treatment studies (with 816 children enrolled). One treatment study was excluded after the sensitivity analysis. From the 14 prevention studies included, the pooled relative risk ratio of AD in those treated with probiotics versus placebo was 0.70 [95% confidence interval (CI) 0.57–0.84; P = 0.0002]. Subgroup analyses showed that only mixed strains of probiotics had a significant effect on lowering the incidence of AD. Probiotics administered solely to infants did not prevent the development of AD, but effects were significant when probiotics were administered to both pregnant mothers and their infants or solely to pregnant mothers. In studies with treatment durations > 6 months, the incidence of AD decreased significantly; a similar effect was achieved when the treatment duration was < 6 months. Meta-analysis of the ten treatment studies showed a significant decrease in the weighted mean difference (WMD) in Scoring Atopic Dermatitis (SCORAD) index values in the probiotics group compared with the control group (WMD, − 7.23; 95% CI − 10.59 to − 3.88; P < 0.0001). Subgroup analyses showed that both single-strain and mixed-strain probiotics had a significant effect on improving SCORAD values. Studies with participants aged < 1 year (P = 0.07) reported no significant results. In studies with treatment periods > 8 weeks, SCORAD values seemed to decrease more than in studies with treatment periods < 8 weeks. However, the subgroup difference was only statistically significant when the analysis was performed according to participant age in prevention studies. Conclusion Our updated meta-analysis demonstrates that interventions with probiotics potentially lower the incidence of AD and relieve AD symptoms in children, particularly when treating infants and children aged ≥ 1 year with AD. Interventions with mixed-strain probiotics tended to have better preventive and curative effects. Probiotics administered solely to infants appeared to produce negative preventive effects. Different intervention durations might also affect clinical outcomes. However, given the insignificant subgroup differences, except for treatment by participant age, and the moderate heterogeneity among the studies, these conclusions should be interpreted with caution, and more powerful randomized controlled trials using standardized measurements should be conducted to assess the long-term effects of probiotics.

Oocyte quality is one of the most important factors involving in female reproduction. The number of compromised oocytes will increase with maternal age, while mitochondrial dysfunction has implicated in age-related poor oocyte. Together with the successful application of ooplasmic transfer (OT) and the critical role of mitochondria in the oocyte, functional mitochondria transfer may be a feasible strategy to improve oocyte quality. However, limitation on ethics and laws are strictly and optimal condition or methods to exert transferring need to be further explored. Therefore, the role of oocyte mitochondria and the effective molecular involving in oocyte quality will be hot topics in next few years. In this review, we summarize the potential mechanism of mitochondria in oocyte and embryo development and discuss the next step for mitochondrial transfer therapy.