Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) and mitochondria play a critical role in growth factor-induced switch from a quiescent to an angiogenic phenotype in endothelial cells ...(ECs). However, how highly diffusible ROS produced from different sources can coordinate to stimulate VEGF signaling and drive the angiogenic process remains unknown. Using the cytosol- and mitochondria-targeted redox-sensitive RoGFP biosensors with real-time imaging, here we show that VEGF stimulation in human ECs rapidly increases cytosolic RoGFP oxidation within 1 min, followed by mitochondrial RoGFP oxidation within 5 min, which continues at least for 60 min. Silencing of Nox4 or Nox2 or overexpression of mitochondria-targeted catalase significantly inhibits VEGF-induced tyrosine phosphorylation of VEGF receptor type 2 (VEGFR2-pY), EC migration and proliferation at the similar extent. Exogenous hydrogen peroxide (H
O
) or overexpression of Nox4, which produces H
O
, increases mitochondrial ROS (mtROS), which is prevented by Nox2 siRNA, suggesting that Nox2 senses Nox4-derived H
O
to promote mtROS production. Mechanistically, H
O
increases S36 phosphorylation of p66Shc, a key mtROS regulator, which is inhibited by siNox2, but not by siNox4. Moreover, Nox2 or Nox4 knockdown or overexpression of S36 phosphorylation-defective mutant p66Shc(S36A) inhibits VEGF-induced mtROS, VEGFR2-pY, EC migration, and proliferation. In summary, Nox4-derived H
O
in part activates Nox2 to increase mtROS via pSer36-p66Shc, thereby enhancing VEGFR2 signaling and angiogenesis in ECs. This may represent a novel feed-forward mechanism of ROS-induced ROS release orchestrated by the Nox4/Nox2/pSer36-p66Shc/mtROS axis, which drives sustained activation of angiogenesis signaling program.
The impact of coronavirus disease 2019 (COVID-19) has profoundly affected education, with most universities changing face-to-face classes to online formats. To adapt to the COVID-19 pandemic ...situation, we adopted a blended learning approach to anatomy instruction that included online lectures, pre-recorded laboratory dissection videos, and 3D anatomy applications, with condensed offline cadaver dissection.
We aimed to examine the learning outcomes of a newly adopted anatomy educational approach by 1) comparing academic achievement between the blended learning group (the 2020 class, 108 students) and the traditional classroom learning group (the 2019 class, 104 students), and 2) an online questionnaire survey on student preference on the learning method and reasons of preference.
The average anatomy examination scores of the 2020 class, who took online lectures and blended dissection laboratories, were significantly higher than those of the 2019 class, who participated in an offline lecture and dissection laboratories. The questionnaire survey revealed that students preferred online lectures over traditional large group lecture-based teaching because it allowed them to acquire increased self-study time, study according to their individual learning styles, and repeatedly review lecture videos.
This study suggests that a blended learning approach is an effective method for anatomy learning, and the advantage may result from increased self-directed study through online learning.
Background
Work‐life conflict (WLC) has a critical effect on employee mental health. However, research on occupational health has neglected the family domain. Furthermore, although it is reasonable ...to assume that the effect of WLC on health may differ according to socioeconomic circumstances, there is little empirical evidence for differences in the impact of WLC by socioeconomic status (SES). The purpose of this study was to assess the role of SES as an effect modifier, while examining whether the SES level affects the relationship between WLC and mental health.
Method
We analyzed data from the nationally representative South Korean Working Conditions Survey of 2014, including 49 401 workers. Logistic regression analyses, stratified by sexes, were performed to identify sex differences, and interaction terms including WLC and SES were also incorporated.
Results
WLC (men: OR = 1.24; women: OR = 1.18) and domestic demands (men: OR = 1.16; women: OR = 1.22) were significantly associated with mental health. WLC exhibited a stronger association with mental health for individuals with high SES, both in terms of education (men: OR = 1.61 vs 1.51; women: OR = 1.52 vs 1.24) and income (men: OR = 1.44 vs 1.10; women: OR = 1.48 vs 1.20).
Conclusions
Our data suggest that future efforts for health promotion should consider workers’ family demands and SES as important modifying factors of psychological health in the workplace.
Endothelial barrier integrity is ensured by the stability of the adherens junction (AJ) complexes comprised of vascular endothelial (VE)-cadherin as well as accessory proteins such as β-catenin and ...p120-catenin. Disruption of the endothelial barrier due to disassembly of AJs results in tissue edema and the influx of inflammatory cells. Using three-dimensional structured illumination microscopy, we observe that the mitochondrial protein Mitofusin-2 (Mfn2) co-localizes at the plasma membrane with VE-cadherin and β-catenin in endothelial cells during homeostasis. Upon inflammatory stimulation, Mfn2 is sulfenylated, the Mfn2/β-catenin complex disassociates from the AJs and Mfn2 accumulates in the nucleus where Mfn2 negatively regulates the transcriptional activity of β-catenin. Endothelial-specific deletion of Mfn2 results in inflammatory activation, indicating an anti-inflammatory role of Mfn2 in vivo. Our results suggest that Mfn2 acts in a non-canonical manner to suppress the inflammatory response by stabilizing cell-cell adherens junctions and by binding to the transcriptional activator β-catenin.
It is well known that polyelectrolyte complexes and coacervates can form on mixing oppositely charged polyelectrolytes in aqueous solutions, due to mainly electrostatic attraction between the ...oppositely charged polymers. Here, we report the first (to the best of our knowledge) complexation and coacervation of two positively charged polyelectrolytes, which provides a new paradigm for engineering strong, self-healing interactions between polyelectrolytes underwater and a new marine mussel-inspired underwater adhesion mechanism. Unlike the conventional complex coacervate, the like-charged coacervate is aggregated by strong short-range cation–π interactions by overcoming repulsive electrostatic interactions. The resultant phase of the like-charged coacervate comprises a thin and fragile polyelectrolyte framework and round and regular pores, implying a strong electrostatic correlation among the polyelectrolyte frameworks. The like-charged coacervate possesses a very low interfacial tension, which enables this highly positively charged coacervate to be applied to capture, carry, or encapsulate anionic biomolecules and particles with a broad range of applications.
In recent years, researchers have been examining the impact of work-life balance (WLB) on mental health, considering it as a potential risk factor. However, it remains unclear whether the traditional ...understanding of WLB applies to older adults who worked for fewer hours before full retirement and whose children are likely to be independent adults. Therefore, this study aims to propose a modified form of WLB specifically for older adults. Within this context, we hypothesize that an optimum balance between working hours and social engagement protects against depressive symptoms among older adults.
We conducted an analysis using data on 5,751 Korean adults older than 55 years from the Korean Longitudinal Study of Aging 2016. Multivariate logistic regression analysis was used to evaluate the relationships among working hours, social engagement, and depressive symptoms.
Older adults who worked fewer than 35 h per week were less likely to experience depressive symptoms than were non-working older adults and those working 35 h or more per week. Additionally, older adults with a high level of informal social participation, thus occurring almost every day or two to three times per week, were less likely to experience depressive symptoms than were those with a low level of such participation (once a month or less). Furthermore, depressive symptoms were less frequent among those who worked fewer than 35 h per week and engaged in a high level of informal social participation compared to non-working older individuals and those with a low level of informal social participation.
Maintaining an optimal number of working hours and degree of social engagement are necessary to minimize the risk of depressive symptoms in older adults. Based on these findings, we suggest that fulfillment for work and life and their balance are important for older adults and propose work-life fulfillment balance.
Vascular endothelial growth factor receptor type 2 (VEGFR2, also known as KDR and FLK1) signalling in endothelial cells (ECs) is essential for developmental and reparative angiogenesis. Reactive ...oxygen species and copper (Cu) are also involved in these processes. However, their inter-relationship is poorly understood. Evidence of the role of the endothelial Cu importer CTR1 (also known as SLC31A1) in VEGFR2 signalling and angiogenesis in vivo is lacking. Here, we show that CTR1 functions as a redox sensor to promote angiogenesis in ECs. CTR1-depleted ECs showed reduced VEGF-induced VEGFR2 signalling and angiogenic responses. Mechanistically, CTR1 was rapidly sulfenylated at Cys189 at its cytosolic C terminus after stimulation with VEGF, which induced CTR1-VEGFR2 disulfide bond formation and their co-internalization to early endosomes, driving sustained VEGFR2 signalling. In vivo, EC-specific Ctr1-deficient mice or CRISPR-Cas9-generated redox-dead Ctr1(C187A)-knockin mutant mice had impaired developmental and reparative angiogenesis. Thus, oxidation of CTR1 at Cys189 promotes VEGFR2 internalization and signalling to enhance angiogenesis. Our study uncovers an important mechanism for sensing reactive oxygen species through CTR1 to drive neovascularization.
MicroRNAs (miRNAs) of urine exosomes have emerged as biomarkers for urological cancers, owing to their high stability. MiRNAs have been linked to factors associated with aggressive prostate cancer ...such as biochemical recurrence (BCR) and metastasis. In this study, we aimed to identify urinary exosomal miRNAs as prognostic markers associated with BCR in intermediate-risk prostate cancer. We profiled the expression levels of miRNAs via next generation sequencing in urinary exosomes from 21 non-BCR patients and 6 BCR patients of intermediate-risk prostate cancer. A total of 21 urinary exosomal miRNAs were found to be differentially expressed (> twofold) in BCR patients compared to non-BCR patients. For external validation, we validated these results using quantitative reverse transcription PCR in an independent cohort of 28 non-BCR patients and 26 BCR patients. A validation analysis revealed that three miRNAs (miR-26a-5p, miR-532-5p, and miR-99b-3p) were upregulated in exosomes from BCR patients. The univariate and multivariate Cox regression analyses showed that miR-532-5p was an important predictive factor for BCR of intermediate-risk prostate cancer. In conclusion, miR-532-5p in urine exosomes might be a potential biomarker for predicting BCR, which is a poor prognosis in patients with intermediate-risk prostate cancer. Further research is needed on the biological functions and mechanisms of this miRNA.
Epigallocatechin-3-gallate (EGCG) is a green tea polyphenol exerting potent anti-oxidant and anti-inflammatory effects by inhibiting signaling and gene expression. The objective of the study was to ...evaluate the effect of EGCG on interleukin (IL)-1 receptor antagonist knockout (IL-1RaKO) autoimmune arthritis models. IL-1RaKO arthritis models were injected intraperitoneally with EGCG three times per week after the first immunization. EGCG decreased the arthritis index and showed protective effects against joint destruction in the IL-1RaKO arthritis models. The expression of pro-inflammatory cytokines, oxidative stress proteins, and p-STAT3 (Y705) and p-STAT3 (S727), mTOR and HIF-1α were significantly lower in mice treated with EGCG. EGCG reduced osteoclast markers in vivo and in vitro along with anti-osteoclastic activity was observed in EGCG-treated IL-1RaKO mice. The proportion of Foxp3(+) Treg cells increased in the spleens of mice treated with EGCG, whereas the proportion of Th17 cells reduced. In vitro, p-STAT3 (Y705) and p-STAT3 (S727), HIF1α and glycolytic pathway molecules were decreased by EGCG. EGCG suppressed the activation of mTOR and subsequently HIF-1α, which is considered as a metabolic check point of Th17/Treg differentiation supporting the therapeutic potential of EGCG in autoimmune arthritis.
Employed workers often have family responsibilities such as childcare or homemaking. This dual burden may increase work-related health problems, particularly if there are conflicts between work and ...family responsibilities. This study assessed whether difficulty in work-life balance is associated with musculoskeletal disorders (MSD) among Korean employees. Data from the population-based Korean Working Conditions Survey of 2011, including 28,640 male and 21,392 female workers, were used. Men and women were analyzed separately to investigate gender differences. MSD were defined as pain in the back, neck, shoulder, or extremities during the past year. Self-assessed difficulty in work-life balance was defined as a work-life conflict (WLC). Adjustments for physical factors, as well as other occupational and socio-demographic variables, were made using multiple logistic regression analysis. Interaction terms including WLCs and key covariates were also incorporated. WLC was significantly associated with increased frequency of MSD in both men (OR: 1.49) and women (OR: 1.50). There were significant interaction effects between WLC and some key covariates (job stress for men and job stress, work hours, physical demand, and frequent overtime work for women). We suggest that having the flexibility to coordinate work and family life is important to prevent MSD among employees.
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