Nitric Oxide Synthase-3 Promotes Embryonic Development of Atrioventricular Valves

Nitric oxide synthase-3 (NOS3) has recently been shown to promote endothelial-to-mesenchymal transition (EndMT) in the developing atrioventricular (AV) canal. The present study was aimed to investigate the role of NOS3 in embryonic development of AV valves. We hypothesized that NOS3 promotes embryonic development of AV valves via EndMT. To test this hypothesis, morphological and functional analysis of AV valves were performed in wild-type (WT) and NOS3^−/− mice at postnatal day 0. Our data show that the overall size and length of mitral and tricuspid valves were decreased in NOS3^−/− compared with WT mice. Echocardiographic assessment showed significant regurgitation of mitral and tricuspid valves during systole in NOS3^−/− mice. These phenotypes were all rescued by cardiac specific NOS3 overexpression. To assess EndMT, immunostaining of Snail1 was performed in the embryonic heart. Both total mesenchymal and Snail1⁺ cells in the AV cushion were decreased in NOS3^−/− compared with WT mice at E10.5 and E12.5, which was completely restored by cardiac specific NOS3 overexpression. In cultured embryonic hearts, NOS3 promoted transforming growth factor (TGFβ), bone morphogenetic protein (BMP2) and Snail1expression through cGMP. Furthermore, mesenchymal cell formation and migration from cultured AV cushion explants were decreased in the NOS3^−/− compared with WT mice. We conclude that NOS3 promotes AV valve formation during embryonic heart development and deficiency in NOS3 results in AV valve insufficiency.     

Noise Exposure and Hearing Impairment among Chinese Restaurant Workers and Entertainment Employees in Hong Kong

Background

Noise-induced hearing loss (NIHL) is a major concern in the non-manufacturing industries. This study aimed to investigate the occupational noise exposure and the NIHL among Chinese restaurant workers and entertainment employees working in the service industry in Hong Kong.

Methods

This cross-sectional survey involved a total of 1,670 participants. Among them, 937 were randomly selected from the workers of Chinese restaurants and 733 were selected from workers in three entertainment sectors: radio and television stations; cultural performance halls or auditoria of the Leisure and Cultural Services Department (LCSD); and karaoke bars. Noise exposure levels were measured in the sampled restaurants and entertainment sectors. Each participant received an audiometric screening test. Those who were found to have abnormalities were required to take another diagnostic test in the health center. The “Klockhoff digit” method was used to classify NIHL in the present study.

Results

The main source of noise inside restaurants was the stoves. The mean hearing thresholds showed a typical dip at 3 to 6 KHz and a substantial proportion (23.7%) of the workers fulfilled the criteria for presumptive NIHL. For entertainment sectors, employees in radio and television stations generally had higher exposure levels than those in the halls or auditoria of the LCSD and karaoke bars. The mean hearing thresholds showed a typical dip at 6 KHz and a substantial proportion of the employees fulfilled the criteria for presumptive NIHL (38.6%, 95%CI: 35.1–42.1%). Being male, older, and having longer service and daily alcohol consumption were associated with noise-induced hearing impairment both in restaurant workers and entertainment employees.

Conclusion

Excessive noise exposure is common in the Chinese restaurant and entertainment industries and a substantial proportion of restaurant workers and entertainment employees suffer from NIHL. Comprehensive hearing conservation programs should be introduced to the service industry in Hong Kong.     

Polymorphism of ORM1 Is Associated with the Pharmacokinetics of Telmisartan

Background

The pharmacokinetics (PKs) and pharmacodynamics (PDs) of telmisartan varies among the individuals, and the main causes remain unknown. The aim of this study was to evaluate the impact of ORM1, as well as ABCC2, ABCB1, ABCG2 and SLCO1B3 polymorphisms, on the disposition of the drug and BP change after taking 40 mg telmisartan in 48 healthy Chinese males.

Method

A total of 48 healthy males were included in this trial. Every volunteer ingested a single dose of 40 mg telmisartan, and the plasma drug concentration and blood pressure (BP) were measured up to 48 h.

Result

In this study, the area under the plasma concentration-time curve (AUC) in the heterozygotes of ORM1 113AG was higher than that in the wild-type homozygotes, AUC_(0–48) (113AA vs. 113AG, 1,549.18±859.84 ng·h/ml vs. 2,313.54±1,257.71 ng·h/ml, P = 0.033), AUC_(0–∞) (113AA vs. 113AG, 1,753.13±1,060.60 ng·h/ml vs. 2,686.90±1,401.87 ng·h/ml, P = 0.016), and the change(%) of the diastolic blood pressure (DBP) from the baseline BP value also showed a significant difference between the ORM1 113AG and 113AA genotypes at 5 h after taking telmisartan (P = 0.026). This study also showed that the allele of ABCC2 C3972T would affected the disposition of telmsiartan and the DBP change significantly after taking the drug. However, the common SNPs of ABCG2 C421, ABCB1 C3435T, and SLCO1B3 T334G showed no impacts on the PKs of telmisartan or BP change(%) in our trial.

Conclusion

The ORM1 A113G polymorphism was associated with the PKs variability after taking telmsiartan, as well as ABCC2 C3972T. The heterozygotes of ORM1 113AG showed a larger AUC and a notable BP change(%) from the baseline compared with the wild-type.

Trial Registration

Chinese Clinical Trial Registry ChiCTR-TNC-10000898     

Circulating Serum Trefoil Factor 3 (TFF3) Is Dramatically Increased in Chronic Kidney Disease

Objectives

Trefoil factor 3 (TFF3) is a small peptide that plays an important role in mucosal protection, cell proliferation, and cell migration. The aberrant expression of TFF3 is correlated with gastrointestinal inflammation, solid tumors, and other clinical diseases. The objective of this study was to identify the distribution characteristics of serum TFF3 in common clinical diseases.

Materials and Methods

A large prospective randomized study of 1,072 Chinese patients was performed using an enzyme-linked immunosorbent assay (ELISA) to examine the serum TFF3 concentrations in patients with different diseases. A matched case-control study was conducted on patients with chronic kidney disease (CKD) stages 1–5. Immunohistochemistry (IHC) was performed using renal tissues to determine the relationship between the severity of CKD and the serum and urine concentrations of TFF3 peptides.

Results

The mean serum concentrations of TFF3 in patients with CKD, metastatic and secondary carcinoma (MC) and acute gastroenteritis (AG) (200.9 ng/ml, 95.7 ng/ml and 71.7 ng/ml, respectively) were significantly higher than those in patients with other common clinical diseases. A positive correlation tendency was observed between the serum TFF3 concentrations and the severity of CKD. The mean serum TFF3 values for CKD stages 1–5 were 23.6 ng/ml, 29.9 ng/ml, 54.9 ng/ml, 85.0 ng/ml and 176.6 ng/ml, respectively. The same trend was observed in the urine TFF3 concentrations and the CKD stages. The creatinine(Cr)-corrected concentrations of TFF3 in urine were 367.1 ng/mg·Cr, 910.6 ng/mg·Cr, 1,149.0 ng/mg·Cr, 1,610.0 ng/mg·Cr and 3,475.0 ng/mg·Cr for CKD stages 1–5, respectively. IHC revealed that TFF3 expression was concentrated in tubular epithelial cells.

Conclusions

The influence of kidney injuries must be fully considered when performing clinical TFF3 research. Further studies on TFF3 in CKD will contribute to our understanding of its pathological roles and mechanisms in other diseases.     

Loss of rice PARAQUAT TOLERANCE 3 confers enhanced resistance to abiotic stresses and increases grain yield in field

Plants frequently suffer from environmental stresses in nature and have evolved sophisticated and efficient mechanisms to cope with the stresses. To balance between growth and stress response, plants are equipped with efficient means to switch off the activated stress responses when stresses diminish. We previously revealed such an off-switch mechanism conferred by Arabidopsis PARAQUAT TOLERANCE 3 (AtPQT3) encoding an E3 ubiquitin ligase, knockout of which significantly enhances resistance to abiotic stresses. To explore whether the rice homologue OsPQT3 is functionally conserved, we generated three knockout mutants with CRISPR-Cas9 technology. The OsPQT3 knockout mutants (ospqt3) display enhanced resistance to oxidative and salt stress with elevated expression of OsGPX1, OsAPX1 and OsSOD1. More importantly, the ospqt3 mutants show significantly enhanced agronomic performance with higher yield compared with the wild type under salt stress in greenhouse as well as in field conditions. We further showed that OsPQT3 expression rapidly decreased in response to oxidative and other abiotic stresses as AtPQT3 does. Taken together, these results show that OsPQT3 is functionally well conserved in rice as an off-switch in stress response as AtPQT3 in Arabidopsis. Therefore, PQT3 locus provides a promising candidate for crop improvement with enhanced stress resistance by gene editing technology.     

Long-Term Exposure to Low-Dose Lead Induced Deterioration in Bone Microstructure of Male Mice

Biological Trace Element Research - The aim of this study was to investigate the long-term effects of low-dose lead exposure on bone microstructure in mice. Ten SPF 12-week-old male C57BL/6J mice...     

脱发相关差异表达基因的生物信息学分析

利用生物信息学方法分析脱发相关差异表达基因,有望帮助了解脱发发生发展的分子机制。本研究从NCBI的子数据库GEO中选择基因表达谱GSE45512和GSE45513数据集,利用R语言limma工具包,筛选出两个物种斑秃样本与正常样本的共同显著差异表达基因。对这部分基因进行功能注释和蛋白互作网络分析,同时对全部差异表达基因进行基因集富集分析。结果发现,人头皮斑秃样本共筛选出225个差异表达基因;C3H/HeJ小鼠自发斑秃皮肤样本共筛选出337个差异表达基因;两个物种的共同显著差异表达基因有23个。GO功能富集分析和蛋白互作网络分析显示,这部分差异基因显著富集于免疫相关功能,并且彼此间存在蛋白互作关系。基因集富集分析显示两个物种的差异基因都能显著富集到趋化因子信号通路、细胞因子受体相互作用、金葡菌感染及抗原加工与呈递通路;而且人的下调差异基因不仅映射到了人类表型数据库的脱发表型,也映射到皮肤附属物病理相关表型。综上所述,本研究通过生物信息方法分析脱发皮肤组织与正常皮肤组织的差异表达基因,最终筛选出23个在人和小鼠中共同存在的显著差异表达基因;此外,分析发现脱发与免疫过程及皮肤附属物病变密切相关,这些结果为脱发的诊断和治疗提供了新思路。