Xanthohumol ameliorates 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin–induced cellular toxicity in cultured MC3T3‐E1 osteoblastic cells

2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) is an environmental contaminant. Xanthohumol is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The aim of the current study was to explore the role of xanthohumol in modulating the toxicity of TCDD in MC3T3‐E1 osteoblastic cells. In cells treated with TCDD alone, intracellular Ca²⁺ concentrations, mitochondrial membrane potential disruption, reactive oxygen species production, cardiolipin peroxidation, nitric oxide release and cytochrome P450 1A1 expression were significantly increased. TCDD treatment increased the mRNA levels of extracellular signal‐regulated kinase 1 and nuclear factor kappa B, and significantly decreased the level of protein kinase B (AKT) in MC3T3‐E1 osteoblastic cells. However, the presence of xanthohumol alleviated the pathological effects of TCDD. In addition, xanthohumol treatment significantly increased the expression of genes associated with osteoblast differentiation (alkaline phosphatase, osteocalcin, osteoprotegerin and osterix). We conclude that xanthohumol has a beneficial influence and may antagonize TCDD toxicity in osteoblastic cells.     

Health service utilization,unmet healthcare needs,and the potential of telemedicine services among Korean expatriates

Background

With the significant growth of migration and expatriation, facilitated by increased global mobility, the number of Koreans living abroad as of 2016 is approximately 7.4 million (15% of the Korean population). Healthcare utilization or health problems, especially among expatriates in developing countries, have not been well researched despite the various health risks these individuals are exposed to. Consequently, we identified the health utilization patterns and healthcare needs among Korean expatriates in Vietnam, Cambodia, and Uzbekistan.

Methods

This cross-sectional survey examined 429 Korean expatriates living in Vietnam (n?=?208), Cambodia (n?=?60), and Uzbekistan (n?=?161) who had access to the Internet and were living abroad for at least 6?months. A 67-item questionnaire was used, and feedback was received via an online survey program. Stepwise logistic regression analyses were performed to evaluate factors associated with unmet healthcare needs and preferences of certain type of telemedicine.

Results

We found that 45.5% (195/429) of respondents had used medical services in their country of stay. Among those who visited health institutions >?3 times, the most popular choice was general hospitals (39.4%, 15/38); however, they initially visited Korean doctors’ or local doctors’ offices. The most essential criteria for healthcare service facilities was a “skilled professional” (39.3%, 169/429), 42% wanted a health program for chronic disease management, and 30% wanted specialized internal medicine. A substantial number wanted to access telemedicine services and were willing to pay for this service. They were particularly interested in experts’ second opinion (61.5%, 264/429) and quick, 24-h medical consultations (60.8%, 261/429). Having unmet healthcare needs and being younger was strongly associated with all types of telemedicine networks.

Conclusions

Nearly half of the expatriates in developing countries had unmet healthcare needs. Telemedicine is one potential solution to meet these needs, especially in developing countries.

     

Spontaneous regression of congenital corneal opacity

Graefe's Archive for Clinical and Experimental Ophthalmology - To determine the incidence of spontaneous regression of congenital corneal opacity (CCO) and identify clinical factors associated...     

External validation of the post-varicocele repair semen analysis nomogram to predict total motile sperm count: A multicenter study

Total motile sperm count is an important parameter for predicting the probability of natural pregnancy. We have externally validated the Samplaski's post-varicocele repair semen analysis nomogram to confirm the predictive accuracy of total motile sperm count. A total of 300 patients who had undergone varicocelectomy between July 2016 and July 2019 from 4 treatment centres were included in this validation cohort study. The predictive performance of the externally validated nomogram was revealed by applying the Pearson correlation coefficient (R = 0.328; 95% confidence interval (CI) 0.220–0.435; p < .001). Compared to Samplaski's nomogram result (R = 0.581; 95% CI 0.186–0.729), our study also revealed a statistically significant rate. However, it had a relatively lower correlation coefficient rate. Notably, the predicted total motile sperm count was lower than the observed post-varicocelectomy total motile sperm count. The calibration plot revealed that the discrepancy between the predicted and observed total motile sperm count was plausible. However, it had low explanatory power in this nomogram model. This validation study demonstrates that the post-varicocele repair Samplaski's nomogram predicts a relatively lower total motile sperm count than the observed count.     

血管内皮生长因子与运动的相关性

目的:血管内皮生长因子是一种广泛存在于机体组织的细胞因子,与运动密切相关,是近来运动人体科学界和运动医学界研究的焦点。对近来血管内皮生长因子与运动的相关研究进行综述,以能够找到提高训练质量乃至运动水平的方法。资料来源:应用计算机检索Medscape.net1996-01/2006-12的相关文章,并根据相关的参考文献检索了部分文章,检索词“vascular endothelial growth factor,exercise”,限定语言种类为English;同时计算机检索中国知识资源总库1996-01/2006-12的相关文献,限定语言种类为中文,检索词“血管内皮生长因子,运动”。资料选择:纳入条件:①随机对照试验研究。②试验包括对照组和干预组。同时排除综述和重复的研究。资料提炼:共找到相关研究47篇,排除17篇,30篇符合标准。通过30个实验对运动中血管内皮生长因子在机体中的表达、作用及含量和动态变化进行了相关的分析和研究。资料综合:①血管内皮生长因子与运动的关系密切相关,现在仍然是运动医学界的研究焦点之一,研究的方向为运动对机体血管内皮生长因子的影响,目的是发现运动对机体的影响。②不同的运动方式对机体的血管内皮生长因子的表达不同,目前采用的训练方式多为极限运动或运动与其他因素相结合,如低压强 运动。③观察部位多集中在大脑、肌肉、心血管、血液等,不同部位的表达不同。④运动对血管内皮生长因子表达有动态变化的规律。结论:血管内皮生长因子与运动的关系密切相关,不同的运动方式会造成血管内皮生长因子在机体不同部位不同表达。运动对血管内皮生长因子表达的影响呈现出规律性。     

An Activin A/BMP2 Chimera,AB204, Displays Bone‐Healing Properties Superior to Those of BMP2

Recombinant bone morphogenetic protein 2 (rhBMP2) has been used clinically to treat bone fractures in human patients. However, the high doses of rhBMP2 required for a therapeutic response can cause undesirable side effects. Here, we demonstrate that a novel Activin A/BMP2 (AB2) chimera, AB204, promotes osteogenesis and bone healing much more potently and effectively than rhBMP2. Remarkably, 1 month of AB204 treatment completely heals tibial and calvarial defects of critical size in mice at a concentration 10‐fold lower than a dose of rhBMP2 that only partially heals the defect. We determine the structure of AB204 to 2.3 Å that reveals a distinct BMP2‐like fold in which the Activin A sequence segments confer insensitivity to the BMP2 antagonist Noggin and an affinity for the Activin/BMP type II receptor ActRII that is 100‐fold greater than that of BMP2. The structure also led to our identification of a single Activin A‐derived amino acid residue, which, when mutated to the corresponding BMP2 residue, resulted in a significant increase in the affinity of AB204 for its type I receptor BMPRIa and a further enhancement in AB204's osteogenic potency. Together, these findings demonstrate that rationally designed AB2 chimeras can provide BMP2 substitutes with enhanced potency for treating non‐union bone fractures. © 2014 American Society for Bone and Mineral Research.     

What Does a Mathematical Model Tell About the Impact of Reinfection in Korean Tuberculosis Infection?

Objectives

According to the Korea Centers for Disease Control and Prevention, new active tuberculosis (TB) cases have increased since 2001. Some key factors explain and characterize the transmission dynamics of Korean TB infection, such as a higher ratio of latent individuals and a new reporting system implemented in 2001, among others.

Methods

We propose a mathematical TB model that includes exogenous reinfection to gain a better understanding of the recent trend for TB incidence. We divide the simulation time window into two periods, 1970–2000 and 2001–2012, according to the implementation date of a new TB detection system.

Results

Two sets of parameters, including the transmission rate, the latent period, the recovery rate, and the proportion of exogenous reinfection, are estimated using the least-squares method and calibrated to data on the incidence of active TB.

Conclusion

Among some key parameters in the model, the case finding effort turned out to be the most significant impacting component on the reduction in the active TB cases.     

巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid

We report the crystal structure of the glycosylated ligand-binding (S1S2) domain of the kainate receptor subunit GluR6, in complex with the agonist domoate. The structure shows the expected overall homology with AMPA and NMDA receptor subunit structures but reveals an unexpected binding mode for the side chain of domoate, in which contact is made to the larger lobe only (lobe I). In common with the AMPA receptor subunit GluR2, the GluR6 S1S2 domain associates as a dimer, with many of the interdimer contacts being conserved. Subtle differences in these contacts provide a structural explanation for why GluR2 L483Y and GluR3 L507Y are nondesensitizing, but GluR6, which has a tyrosine at that site, is not. The structure incorporates native glycosylation, which has not previously been described for ionotropic glutamate receptors. The position of the sugars near the subunit interface rules out their direct involvement in subunit association but leaves open the possibility of indirect modulation. Finally, we observed several tetrameric assemblies that satisfy topological constraints with respect to connection to the receptor pore, and which are therefore candidates for the native quaternary structure.