Explore the vast range of titles available.

Background 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. Method 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. Results 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. Conclusions 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. Das et al. show that the copper transporter CTR1 functions as a redox sensor in endothelial cells. CTR1 is modified after redox stress, which induces CTR1–VEGFR2 complex formation and promotes VEGFR2 signalling and angiogenesis.

Background The COVID-19 pandemic rapidly accelerated workplace digitalization, significantly heightening concerns about its impact. While the physical risks associated with digitalization, particularly musculoskeletal disorders (MSDs), have been widely studied, research on psychosocial factors—especially concerns about future digitalization—remains relatively limited. This study aimed to assess whether concerns about future digitalization are associated with MSDs, while considering past adoption and current utilization of digital technologies. Additionally, it examined the moderating effects of various factors, including socioeconomic and work-related variables, on this relationship. Methods Data from the 2020 Korean Working Conditions Survey (KWCS), which included a representative sample of 48,604 workers in South Korea, were analyzed. A multiple logistic regression analysis was conducted to explore the association between concerns about future digitalization and MSDs. The model controlled for past adoption and current utilization of digitalization, as well as other relevant covariates. Furthermore, interaction terms with moderating factors were incorporated to investigate potential moderating effects within the model. Results Concerns about future digitalization were significantly associated with the likelihood of MSDs, even after accounting for past adoption and current utilization (OR: 1.08, 95% CI: 1.04–1.14). The impact of these concerns on MSDs was moderated by education level, with higher education levels mitigating the effect (OR: 1.41 for below middle school, 0.85 for high school or college, and 0.71 for university or above). Conclusions Recognizing concerns related to future digitalization as a critical psychosocial risk factor is essential, as they influence the development of MSDs. Future research should focus on alleviating these concerns and enhancing workers’ resilience in increasingly digitalized work environments. These findings underscore the importance for policymakers and employers to incorporate psychosocial considerations into digital transition strategies and to provide targeted support for vulnerable worker populations.

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.

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. Endothelial tissues must have intact barrier function, but this may be disrupted during inflammation. Here, the authors show that the mitochondrial protein Mitofusin-2 stabilizes cell–cell adherens junctions in endothelial cells during homeostasis and binds the transcriptional activator β-catenin upon inflammatory stimulation.

Blood–brain barrier (BBB) dysfunction is emerging as a key pathogenic factor in the progression of Alzheimer’s disease (AD), where increased microvascular endothelial permeability has been proposed to play an important role. However, the molecular mechanisms leading to increased brain microvascular permeability in AD are not fully understood. We studied brain endothelial permeability in female APPswe/PS1∆E9 (APP/PS1) mice which constitute a transgenic mouse model of amyloid-beta (Aβ) amyloidosis and found that permeability increases with aging in the areas showing the greatest amyloid plaque deposition. We performed an unbiased bulk RNA-sequencing analysis of brain endothelial cells (BECs) in female APP/PS1 transgenic mice. We observed that upregulation of interferon signaling gene expression pathways in BECs was among the most prominent transcriptomic signatures in the brain endothelium. Immunofluorescence analysis of isolated BECs from female APP/PS1 mice demonstrated higher levels of the Type I interferon-stimulated gene IFIT2. Immunoblotting of APP/PS1 BECs showed downregulation of the adherens junction protein VE-cadherin. Stimulation of human brain endothelial cells with interferon-β decreased the levels of the adherens junction protein VE-cadherin as well as tight junction proteins Occludin and Claudin-5 and increased barrier leakiness. Depletion of the Type I interferon receptor in human brain endothelial cells prevented interferon-β-induced VE-cadherin downregulation and restored endothelial barrier integrity. Our study suggests that Type I interferon signaling contributes to brain endothelial dysfunction in AD.

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.

Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate the consequences of MI are a high priority. Cardiac progenitor cells (CPCs) have been used to treat cardiac injury post-MI, and despite poor engraftment, they have been shown to inhibit apoptosis and to promote angiogenesis through poorly understood paracrine effects. We previously reported that the direct injection of exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against apoptosis in a model of acute ischemia/reperfusion injury. Moreover, we and others have reported that reactive oxygen species (ROS) derived from NADPH oxidase (NOX) can enhance angiogenesis in endothelial cells (ECs). Here we examined whether bioengineered CPCexo transfected with a pro-angiogenic miR-322 (CPCexo-322) can improve therapeutic efficacy in a mouse model of MI as compared to CPCexo. Systemic administration of CPCexo-322 in mice after ischemic injury provided greater protection post-MI than control CPCexo, in part, through enhanced angiogenesis in the border zones of infarcted hearts. Mechanistically, the treatment of cultured human ECs with CPCexo-322 resulted in a greater angiogenic response, as determined by increased EC migration and capillary tube formation via increased Nox2-derived ROS. Our study reveals that the engineering of CPCexo via microRNA (miR) programing can enhance angiogenesis, and this may be an effective therapeutic strategy for the treatment of ischemic cardiovascular diseases.

Purpose Cancer survivors encounter significant psychological suffering and are prone to develop depressive symptoms. Work contributes to personal fulfillment and social connections, and by doing so, enhances a cancer survivor’s resilience against adversities. However, maintaining employment can be challenging for some cancer survivors. This research aimed to identify the association between changes in work status and depressive symptoms among cancer survivors in South Korea. Methods This study used the panel data from the Korean Longitudinal Study of Ageing (KLoSA) and included 199 cancer survivors–799 observations–aged 65 or younger, between 2005 and 2018. Changes in work status consisted of continuous unemployment or employment, quitting a job, and getting a job. We defined depressive symptoms as a CES-D-10 score of 10 or higher and a cut-off of 4 was utilized for sensitivity analysis. Multivariable generalized estimating equation was employed to estimate the odds ratio (OR), adjusting for the number of household members, education level, sex, age, marital status, occupations, cancer treatment, cancer type, catastrophic healthcare expenditure (CHE), and survivorship. Subgroup analysis and interaction between changes in work and cancer types were further explored. Results For depressive symptoms, the OR of the continuous unemployment group was 2.27 (95% CI = 1.10–4.69), and the OR of the group that quit a job was 2.20 (95% CI = 1.03–4.72), compared to the continuous employment group. As survivorship increased, the odds of depressive symptoms decreased (OR = 0.94, 95% CI = 0.89–1.00). CHE was associated with depressive symptoms (OR = 2.23, 95% CI = 1.18–4.20). In cancer types with a low tendency to depression, continuous unemployment was associated with depressive symptoms (OR = 3.19, 95% CI = 1.12–9.06). In sensitivity analysis, changes in work, survivorship, and CHE were consistently associated with depressive symptoms. Conclusions Cancer survivors who quit a job or continued unemployment were more likely to experience depressive symptoms. The findings of this study imply that assistance for cancer survivors to continue a job or return to employment, including adjustment of workload and hours, may be helpful. Psychological care may be crucial, particularly in the early stage of cancer survivorship. Furthermore, support may be needed to alleviate the burden of healthcare expenditure.

Inotuzumab ozogamicin (InO), a CD22-targeted antibody-drug conjugate, delivers the cytotoxic agent, calicheamicin, to B-cell precursor of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) cells. It has demonstrated efficacy in phase 3 trials, leading to approval in multiple countries, including the U.S., Japan, and South Korea. In our post-marketing surveillance (PMS) study, we evaluated the safety and effectiveness of InO in adults with R/R B-ALL based on approximately 5 years of PMS data. A prospective, observational, multicenter PMS study was conducted in Korea to evaluate the real-world safety and effectiveness of InO in adult patients with R/R B-ALL (NCT04307134). A total of 107 patients were included in the safety analysis, with a median treatment duration of 43.0 days and a median of 2.0 InO cycles. Common adverse events (AEs) were hematologic (58.9%), infectious (50.5%), and gastrointestinal (45.8%), with neutropenia (27.1%) and febrile neutropenia (26.2%) among the most frequent. Serious AEs occurred in 31.8% of patients, most commonly infections such as septic shock (6.5%) and pneumonia (4.7%). Veno-occlusive disease was observed in 2.8% of patients. In the effectiveness analysis set ( N  = 94), median progression-free survival was 3.6 months (95% CI: 3.0–4.7 months), overall survival was 10.2 months (95% CI: 6.0–NA months), and duration of remission was 3.8 months. (95% CI: 3.0–5.4 months). These findings support the clinical utility and safety profile of InO in Korean patients with R/R B-ALL, reflecting real-world outcomes.