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1.
PLoS One ; 19(7): e0305637, 2024.
Article in English | MEDLINE | ID: mdl-39024346

ABSTRACT

INTRODUCTION: Previous studies have extensively examined the relationship between social support and various health outcomes. However, little is known about the distinct longitudinal associations between perceived social support and the development of cardiovascular events in patients with metabolic syndrome. In this cohort study, we investigated whether the levels of perceived social support in patients with metabolic syndrome were associated with an increased risk of cerebrovascular and cardiovascular events. METHODS: The level of social support was assessed using the Medical Outcomes Study-Social Support Survey (MOS-SSS) in 2,721 individuals living in Wonju and Pyeongchang, South Korea. The presence of metabolic syndrome was determined by physical measurements and blood tests, and the occurrence of cerebral cardiovascular disease in relation to the presence of metabolic syndrome and the level of social support was analyzed using Cox proportional-hazards models. RESULTS: The median follow-up period was 2,345 days (2,192-2,618). Overall, in the group with metabolic syndrome and low social support, low social support was associated with an increased risk of later cerebral cardiovascular events; in this group, the hazard ratio after adjusting for confounding variables was 1.97 times (95% confidence interval, 1.01-3.85) higher than that in the group without metabolic syndrome and low social support. CONCLUSION: This study shows, for the first time, that the level of social support is a risk factor for preventing cerebral cardiovascular disease in patients with metabolic syndrome and suggests that social support status should be incorporated into multifactorial risk assessment and intervention procedures to prevent metabolic syndrome and cerebral cardiovascular disease.


Subject(s)
Metabolic Syndrome , Social Support , Humans , Metabolic Syndrome/complications , Metabolic Syndrome/epidemiology , Female , Male , Middle Aged , Republic of Korea/epidemiology , Cohort Studies , Adult , Cardiovascular Diseases , Risk Factors , Aged , Cerebrovascular Disorders/complications , Proportional Hazards Models
2.
J Glaucoma ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38934849

ABSTRACT

PRECIS: Different mechanisms of angle closure represented distinct aspects of intraocular pressure (IOP) control after phacoemulsification. Classification of angle closure mechanisms is necessary for postoperative IOP management and glaucoma progression in primary angle closure eyes. PURPOSE: To investigate the relationship between the anterior chamber angle (ACA) characteristics, measured by swept-source anterior segment optical coherence tomography (SS AS-OCT), and intraocular pressure (IOP) control after phacoemulsification in eyes with primary angle closure disease (PACD) with different angle closure mechanisms. METHODS: PACD eyes were classified into 3 groups according to angle closure mechanisms using preoperative SS AS-OCT images; pupillary block (PB), plateau iris configuration (PIC), exaggerated lens vault (ELV). This retrospective, clinical cohort study included eighty-five eyes of 85 PACD patients: 34 with PB, 23 with PIC, and 28 with ELV. ACA parameters were measured preoperatively and 1 month postoperatively using SS AS-OCT. IOP measurements were performed preoperatively and during six months postoperatively. Postoperative IOP reduction and fluctuation were calculated, and their correlations with SS AS-OCT parameters were analyzed. RESULTS: PIC group showed the lowest postoperative IOP reduction compared to the other groups (P=0.023). Preoperative ACA measurements were significantly associated with postoperative IOP reduction in ELV and PB groups, while postoperative measurements were in PIC group. Preoperative and postoperative change of iridotrabecular contact (ITC) index and area were correlated with postoperative IOP reduction in PB and ELV groups but not in PIC group. Postoperative ITC index (P=0.031) and area (P=0.003) showed significant correlations with postoperative IOP fluctuation only in PIC group. CONCLUSIONS: SS AS-OCT parameters including ITC index and area showed different associations with postoperative IOP control, which should be considered in determination of lens extraction and treatment of PACD eyes.

3.
Yonsei Med J ; 65(6): 363-370, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38804031

ABSTRACT

PURPOSE: We investigated the association between social support, metabolic syndrome, and incident cardio-cerebrovascular disease (CCVD) in rural Koreans aged ≥50 years. MATERIALS AND METHODS: We conducted a prospective study using the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) dataset. From the baseline of 5169 adults, 1682 participants were finally included according to the exclusion criteria. For outcomes, myocardial infarction, angina, and stroke were included. For independent variables, the social support score and metabolic syndrome were used. Descriptive statistics and multivariate logistic regression were performed to investigate the association among the variables. Paired t-test was conducted to analyze the longitudinal variation of social support scores. RESULTS: During the 6.37 years of median follow-up, 137 participants developed CCVD. The adjusted odds ratio (aOR) of metabolic syndrome with persistently high social support was 2.175 [95% confidence interval (CI): 1.479-3.119]. The aOR of metabolic syndrome with persistently low social support was 2.494 (95% CI: 1.141-5.452). The longitudinal variation of the social support score of persistently high social support group was increased significantly by 4.26±26.32. The score of the persistently low social support group was decreased by 1.34±16.87 with no statistical significance. CONCLUSION: The presence of metabolic syndrome increases the likelihood of developing onset CCVD. Within the metabolic syndrome positive group, when social support was persistently low, the cohort developed more cardio-cerebrovascular disease compared to the persistently higher social support group. The social support score of the persistently low social support group could be improved through proper intervention. To prevent CCVD, metabolic syndrome components and low social support should be improved in the study participants.


Subject(s)
Cerebrovascular Disorders , Metabolic Syndrome , Social Support , Humans , Metabolic Syndrome/epidemiology , Female , Male , Middle Aged , Cerebrovascular Disorders/epidemiology , Aged , Prospective Studies , Incidence , Republic of Korea/epidemiology , Risk Factors , Cardiovascular Diseases/epidemiology , Rural Population/statistics & numerical data , Logistic Models , Odds Ratio
4.
Ann Coloproctol ; 40(2): 89-113, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38712437

ABSTRACT

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

5.
Biochem Biophys Res Commun ; 710: 149886, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38581953

ABSTRACT

Mdivi-1, Mitochondrial DIVIsion inhibitor 1, has been widely employed in research under the assumption that it exclusively influences mitochondrial fusion, but effects other than mitochondrial dynamics have been underinvestigated. This paper provides transcriptome and DNA methylome-wide analysis for Mdivi-1 treated SH-SY5Y human neuroblastoma cells using RNA sequencing (RNA-seq) and methyl capture sequencing (MC-seq) methods. Gene ontology analysis of RNA sequences revealed that p53 transcriptional gene network and DNA replication initiation-related genes were significantly up and down-regulated, respectively, showing the correlation with the arrest cell cycle in the G1 phase. MC-seq, a powerful sequencing method for capturing DNA methylation status in CpG sites, revealed that although Mdivi-1 does not induce dramatic DNA methylation change, the subtle alterations were concentrated within the CpG island. Integrative analysis of both sequencing data disclosed that the p53 transcriptional network was activated while the Parkinson's disease pathway was halted. Next, we investigated several changes in mitochondria in response to Mdivi-1. Copy number and transcription of mitochondrial DNA were suppressed. ROS levels increased, and elevated ROS triggered mitochondrial retrograde signaling rather than inducing direct DNA damage. In this study, we could better understand the molecular network of Mdivi-1 by analyzing DNA methylation and mRNA transcription in the nucleus and further investigating various changes in mitochondria, providing inspiration for studying nuclear-mitochondrial communications.


Subject(s)
Dynamins , Neuroblastoma , Humans , Dynamins/metabolism , Mitochondrial Dynamics , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/genetics , Quinazolinones/pharmacology
6.
Lab Chip ; 24(5): 1076-1087, 2024 02 27.
Article in English | MEDLINE | ID: mdl-38372151

ABSTRACT

Limitations with cell cultures and experimental animal-based studies have had the scientific and industrial communities searching for new approaches that can provide reliable human models for applications such as drug development, toxicological assessment, and in vitro pre-clinical evaluation. This has resulted in the development of microfluidic-based cultures that may better represent organs and organ systems in vivo than conventional monolayer cell cultures. Although there is considerable interest from industry and regulatory bodies in this technology, several challenges need to be addressed for it to reach its full potential. Among those is a lack of guidelines and standards. Therefore, a multidisciplinary team of stakeholders was formed, with members from the US Food and Drug Administration (FDA), the National Institute of Standards and Technology (NIST), European Union, academia, and industry, to provide a framework for future development of guidelines/standards governing engineering concepts of organ-on-a-chip models. The result of this work is presented here for interested parties, stakeholders, and other standards development organizations (SDOs) to foster further discussion and enhance the impact and benefits of these efforts.


Subject(s)
Microfluidics , Microphysiological Systems , Animals , Humans , Microfluidics/methods , Cell Culture Techniques , Drug Development , Reference Standards , Lab-On-A-Chip Devices
7.
Article in English | MEDLINE | ID: mdl-38315595

ABSTRACT

The global prevalence of childhood and adolescent obesity is a major concern due to its association with chronic diseases and long-term health risks. Artificial intelligence technology has been identified as a potential solution to accurately predict obesity rates and provide personalized feedback to adolescents. This study highlights the importance of early identification and prevention of obesity-related health issues. To develop effective algorithms for the prediction of obesity rates and provide personalized feedback, factors such as height, weight, waist circumference, calorie intake, physical activity levels, and other relevant health information must be taken into account. Therefore, by collecting health datasets from 321 adolescents who participated in Would You Do It! application, we proposed an adolescent obesity prediction system that provides personalized predictions and assists individuals in making informed health decisions. Our proposed deep learning framework, DeepHealthNet, effectively trains the model using data augmentation techniques, even when daily health data are limited, resulting in improved prediction accuracy (acc: 0.8842). Additionally, the study revealed variations in the prediction of the obesity rate between boys (acc: 0.9320) and girls (acc: 0.9163), allowing the identification of disparities and the determination of the optimal time to provide feedback. Statistical analysis revealed that the performance of the proposed deep learning framework was more statistically significant (p 0.001) compared to the other general models. The proposed system has the potential to effectively address childhood and adolescent obesity.

8.
Lab Chip ; 24(5): 1293-1306, 2024 02 27.
Article in English | MEDLINE | ID: mdl-38230512

ABSTRACT

Microphysiological systems (MPS), also known as miniaturized physiological environments, have been engineered to create and study functional tissue units capable of replicating organ-level responses in specific contexts. The MPS has the potential to provide insights about the safety, characterization, and effectiveness of medical products that are different and complementary to insights gained from traditional testing systems, which can help facilitate the transition of potential medical products from preclinical phases to clinical trials, and eventually to market. While many MPS are versatile and can be used in various applications, most of the current applications have primarily focused on drug discovery and testing. Yet, there is a limited amount of research available that demonstrates the use of MPS in assessing biological products such as cellular and gene therapies. This review paper aims to address this gap by discussing recent technical advancements in MPS and their potential for assessing biological products. We further discuss the challenges and considerations involved in successful translation of MPS into mainstream product testing.


Subject(s)
Biological Products , Microphysiological Systems , Drug Discovery
9.
Exp Eye Res ; 239: 109781, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38184223

ABSTRACT

In addition to regulating cholesterol synthesis, statins have neuroprotective effects. Apoptosis of retinal ganglion cells (RGCs) causes a gradual loss of visual function in glaucoma. This study aimed to investigate the neuroprotective effect of statins on the RGC apoptosis induced by activated Müller glia. Primary Müller cells and RGCs were cultured from the retina of C57BL6 mice. Müller cells were activated with GSK101, a transient receptor potential vanilloid 4 (TRPV4) agonist, and tumor necrosis factor-alpha (TNF-α) released to the medium was measured using an enzyme-linked immunosorbent assay. Cells were pretreated with simvastatin or lovastatin before GSK101. RGCs were treated with conditioned media from Müller glia cultures, and apoptosis was determined using flow cytometry. TRPV4 activation through GSK101 treatment induced gliosis of Müller cells, and the conditioned media from activated Müller cells was potent to induce RGC apoptosis. Statins suppress both gliosis in Müller cells and subsequent RGC apoptosis. TNF-α release to the media was increased in GSK101-treated Müller cells, and TNF-α in the conditioned media was the critical factor causing RGC apoptosis. The increase in TRPV4-mediated TNF-α expression occurred through the nuclear factor kappa-light chain enhancer of activated B cell pathway activation, which was inhibited by statins. Herein, we showed that statins can modulate gliosis and TNF-α expression in Müller cells, protecting RGCs. These data further support the neuroprotective effect of statins, promoting them as a potential treatment for glaucoma.


Subject(s)
Antineoplastic Agents , Glaucoma , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Neuroprotective Agents , Animals , Mice , Antineoplastic Agents/pharmacology , Apoptosis , Culture Media, Conditioned/pharmacology , Ependymoglial Cells/metabolism , Glaucoma/drug therapy , Glaucoma/pathology , Gliosis/pathology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Mice, Inbred C57BL , Neuroprotective Agents/pharmacology , TRPV Cation Channels/metabolism , Tumor Necrosis Factor-alpha/metabolism
10.
Reprod Toxicol ; 123: 108523, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38092131

ABSTRACT

Understanding drug transport across the placental barrier is important for assessing the potential fetal drug toxicity and birth defect risks. Current in vivo and in vitro models have structural and functional limitations in evaluating placental drug transfer and toxicity. Microphysiological systems (MPSs) offer more accurate and relevant physiological models of human tissues and organs on a miniature scale for drug development and toxicology testing. MPSs for the placental barrier have been recently explored to study placental drug transfer. We utilized a multilayered hydrogel membrane-based microphysiological model composed of human placental epithelial and endothelial cells to replicate the key structure and function of the human placental barrier. A macroscale human placental barrier model was created using a transwell to compare the results with the microphysiological model. Placental barrier models were characterized by assessing monolayer formation, intercellular junctions, barrier permeability, and their structural integrity. Three small-molecule drugs (glyburide, rifaximin, and caffeine) that are prescribed or taken during pregnancy were studied for their placental transfer. The results showed that all three drugs crossed the placental barrier, with transfer rates in the following order: glyburide (molecular weight, MW = 494 Da) < rifaximin (MW = 785.9 Da) < caffeine (MW = 194.19 Da). Using non-compartmental analysis, we estimated human pharmacokinetic characteristics based on in vitro data from both MPS and transwell models. While further research is needed, our findings suggest that MPS holds potential as an in vitro tool for studying placental drug transfer and predicting fetal exposure, offering insights into pharmacokinetics.


Subject(s)
Glyburide , Placenta , Humans , Pregnancy , Female , Endothelial Cells , Caffeine , Rifaximin
11.
Am J Ophthalmol ; 257: 57-65, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37634610

ABSTRACT

PURPOSE: To investigate longitudinal changes in the anterior segment (AS) using serial optical coherence tomography (OCT) images and determine the impact of these changes on the anterior chamber angle (ACA) in eyes with primary angle closure disease (PACD) treated with laser peripheral iridotomy (LPI). DESIGN: Retrospective clinical cohort study. METHODS: This study included 103 patients with PACD who underwent LPI and were followed up by a mean 6.7 ± 1.7 AS-OCT examinations for a mean 6.5 ± 2.9 years. Temporal changes in AS-OCT parameters, including anterior chamber depth (ACD), angle opening distance (AOD750), angle recess area (ARA750), iris thickness (IT750), lens vault (LV), and pupil diameter (PD), were analyzed by multivariate linear mixed effects models (LMEMs). RESULTS: Multivariate LMEMs showed that decrease in AOD750 was not significant (-1.59 µm/y, P = .222); however, ARA750 decreased over time (-2.3 × 103 µm2/y, P = .033) and SSA showed marginal significance (-0.20°/y, P = .098), and LV increased significantly (11.6 µm/y, P < .001) after LPI. Mean LV change was negatively associated with AOD750, ARA750, and SSA, whereas PD was negatively associated with ARA750 (P < .001 each). PD decreased with aging (-13.7 µm/y, P = .036), accompanied by thinning of IT750 (-1.7 µm/y, P = .063). CONCLUSIONS: LV tends to increase with aging, which contributes to the shallowing of the anterior chamber and narrowing of ACA in PACD eyes treated with LPI. In the meantime, pupillary constriction and subsequent peripheral iris thinning associated with aging could possibly offset the effect of ACA narrowing.


Subject(s)
Anterior Eye Segment , Glaucoma, Angle-Closure , Humans , Anterior Eye Segment/diagnostic imaging , Iridectomy/methods , Cohort Studies , Retrospective Studies , Intraocular Pressure , Glaucoma, Angle-Closure/diagnosis , Glaucoma, Angle-Closure/surgery , Gonioscopy , Anterior Chamber/diagnostic imaging , Iris/diagnostic imaging , Tomography, Optical Coherence/methods
12.
Sci Rep ; 13(1): 22569, 2023 12 19.
Article in English | MEDLINE | ID: mdl-38114561

ABSTRACT

We investigated the difference in optical coherence tomography angiography characteristics between the patients with compressive optic neuropathy (CON, n = 26) and glaucomatous optic neuropathy (GON, n = 26), who were matched for the severity of visual field defect. The peripapillary retinal nerve fiber layer (pRNFL) thickness in the nasal and temporal sectors was thinner in the CON group, whereas the inferior pRNFL thickness was thinner in the GON group. Accordingly, the CON group had lower peripapillary vessel density (pVD) in the nasal and temporal sectors, and the GON group in the inferior sector. In the macular area, the CON group had a thinner macular ganglion cell-inner plexiform layer in the superior and nasal sectors, whereas the GON group in the inferior sector. However, the CON group did not have a lower macular VD than the GON group in any sector, whereas the GON group exhibited lower superficial capillary plexus VD in the superior, inferior, and temporal sectors. Comparison of the structure-vasculature correlation revealed a significant difference in the nasal and temporal peripapillary areas and superior and nasal macular sectors; a decrease in VD was greater in the GON group than in the CON group when the comparable structural change occurred.


Subject(s)
Glaucoma , Optic Disk , Optic Nerve Diseases , Humans , Optic Disk/diagnostic imaging , Optic Disk/blood supply , Retinal Ganglion Cells , Retina , Optic Nerve Diseases/diagnostic imaging , Glaucoma/diagnostic imaging , Retinal Vessels/diagnostic imaging , Tomography, Optical Coherence/methods
13.
Ann Occup Environ Med ; 35: e17, 2023.
Article in English | MEDLINE | ID: mdl-37928373

ABSTRACT

The current 52-hour workweek in South Korea consists of 40 hours of regular work and 12 hours of overtime. Although the average working hours in South Korea is declining, it is still 199 hours longer than the Organisation for Economic Co-operation and Development average of 1,716 hours per year. In view to this, the South Korean government has now proposed to reform the workweek, mainly intending to increase the workweek to 69 hours when the workload is heavy. This reform, by increasing the labor intensity due to long working hours, goes against the global trend of reducing work hours for a safe and healthy working environment. Long working hours can lead to increased cerebrovascular and cardiovascular diseases, industrial accidents, mental health problems, and safety accidents due to lack of concentration. In conclusion, the Korean government's working hour reform plan can have a negative impact on workers' health, and therefore it should be thoroughly reviewed and modified.

14.
J Anim Sci Technol ; 65(5): 939-950, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37969334

ABSTRACT

This study was conducted to assess the impact of growing condition variables on alfalfa (Medicago sativa L.) productivity. A total of 197 alfalfa yield results were acquired from the alfalfa field trials conducted by the South Korean National Agricultural Cooperative Federation or Rural Development Administration between 1983 and 2008. The corresponding climate and soil data were collected from the database of the Korean Meteorological Administration. Twenty-three growing condition variables were developed as explaining variables for alfalfa forage biomass production. Among them, twelve variables were chosen based on the significance of the partial-correlation coefficients or potential agricultural values. The selected partial correlation coefficients between the variables and alfalfa forage biomass ranged from -0.021 to 0.696. The influence of the selected twelve variables on yearly alfalfa production was summarized into three dominant factors through factor analysis. Along with the accumulated temperature variables, the loading scores of the daily mean temperature higher than 25°C were over 0.88 in factor 1. The sunshine duration at temperature between 0°C-25°C was 0.939 in factor 2. Precipitation days were 0.82, which was the greatest in factor 3. Stepwise regression applied with the three dominant factors resulted in the coefficients of factors 1, 2, and 3 for 0.633, 0.485, and 0.115, respectively, and the R-square of the model was 0.602. The environmental conditions limiting alfalfa growth, such as daily temperature higher than 25°C or daily mean temperature affected annual alfalfa production most substantially among the growing condition variables. Therefore, future cultivar selection should consider the capability of alfalfa to be tolerant to extreme summer weather along with biomass production potential.

15.
Adv Biol (Weinh) ; : e2300131, 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37814378

ABSTRACT

In May 2022, there is an International Regulatory and Pharmaceutical Industry (Innovation and Quality [IQ] Microphysiological Systems [MPS] Affiliate) Workshop on the standardization of complex in vitro models (CIVMs) in drug development. This manuscript summarizes the discussions and conclusions of this joint workshop organized and executed by the IQ MPS Affiliate and the United States Food and Drug Administration (FDA). A key objective of the workshop is to facilitate discussions around opportunities and/or needs for standardization of MPS and chart potential pathways to increase model utilization in the context of regulatory decision making. Participation in the workshop included 200 attendees from the FDA, IQ MPS Affiliate, and 26 global regulatory organizations and affiliated parties representing Europe, Japan, and Canada. It is agreed that understanding global perspectives regarding the readiness of CIVM/MPS models for regulatory decision making and potential pathways to gaining acceptance is useful to align on globally. The obstacles are currently too great to develop standards for every context of use (COU). Instead, it is suggested that a more tractable approach may be to think of broadly applicable standards that can be applied regardless of COU and/or organ system. Considerations and next steps for this effort are described.

16.
Ann Occup Environ Med ; 35: e36, 2023.
Article in English | MEDLINE | ID: mdl-37701485

ABSTRACT

Background: Work-Family Conflict means that the demands of work and family roles cannot be met simultaneously, so one cannot concentrate on one's work or family role. This conflict can negatively affect mental health and cause insomnia symptoms. Methods: This study was conducted on 20,442 subjects. Insomnia symptoms were assessed using the Minimal Insomnia Symptom Scale, and other variables were assessed using the questionnaire method. Logistic regression analyses were performed to evaluate the effect of Work-Family Conflict on insomnia symptoms, and subgroup logistic regression analyses were also performed. Results: The number of people with insomnia symptoms was 4,322 (15.1%). Compared with Low Work-Family Conflict, the odds ratios (ORs) for the risk of insomnia symptoms were 1.84 (95% confidence interval: 1.56-2.16) in High work-to-family conflict, 1.16 (1.02-1.32) in High family-to-work conflict, and 3.19 (2.87-3.55) in High Work-Family Conflict. The ORs were higher for men than women in High WFC but higher for women than men in High Work-Family Conflict. Conclusions: The risk of insomnia symptoms was highest in High Work-Family Conflict.

17.
Bone ; 177: 116918, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37739296

ABSTRACT

Recently improved techniques could provide snapshots of chromatin structure generated based on chromatin accessibility. Since chromatin accessibility determines transcriptional potential, it has been attempted in a variety of cell systems. However, there has been no genome-wide analysis of chromatin accessibility for the entire murine osteoclast (OC) differentiation process. We performed an Assay for Transposase-Accessible Chromatin (ATAC)-sequencing (seq) during RANKL-induced OC differentiation and found that global chromatin accessibility decreased, especially early in OC differentiation. The global histone H3K27Ac level, an active histone modification mark, was diminished during OC differentiation by western blot and histone extract experiments. Its genomic enrichment was also reduced based on publicly available H3K27Ac chromatin immunoprecipitation (ChIP)-seq data. ATAC-seq and H3K27Ac ChIP-seq data demonstrated that RANKL induced a less accessible chromatin state during OC differentiation. Restoration of reduced H3K27Ac, presumably representing accessible states upon acetate treatment, suppresses OC differentiation by provoking immune-related gene expression. Subsequential integrative analysis of ATAC-seq, RNA-seq after acetate treatment, and H3K27Ac ChIP-seq reveals that Irf8 and its downstream targets are the most vulnerable to chromatin accessibility changes and acetate supplementation. Taken together, our study generated chromatin accessibility maps during the whole OC differentiation and suggested perturbation of chromatin accessibility might be a potential therapeutic strategy for excessive OC diseases.

18.
Adv Biol (Weinh) ; : e2300094, 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37409400

ABSTRACT

Mesenchymal stromal cells (MSCs) continue to be proposed for clinical investigation to treat myriad diseases given their purported potential to stimulate endogenous regenerative processes, such as angiogenesis. However, MSC functional heterogeneity has hindered clinical success and still poses a substantial manufacturing challenge from a product quality control perspective. Here, a quantitative bioassay based on an enhanced-throughput is described, microphysiological system (MPS) to measure the specific bioactivity of MSCs to stimulate angiogenesis as a potential measure of MSC potency. Using this novel bioassay, MSCs derived from multiple donors at different passages are co-cultured with human umbilical vein endothelial cells and exhibit significant heterogeneity in angiogenic potency between donors and cell passage. Depending on donor source and cellular passage number, MSCs varied in their ability to stimulate tip cell dominant or stalk cell dominant phenotypes in angiogenic sprout morphology which correlated with expression levels of hepatocyte growth factor (HGF). These findings suggest that MSC angiogenic bioactivity may be considered as a possible potency attribute in MSC quality control strategies. Development of a reliable and functionally relevant potency assay for measuring clinically relevant potency attributes of MSCs will help to improve consistency in quality and thereby, accelerate clinical development of these cell-based products.

19.
J Glaucoma ; 32(11): 918-925, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37523631

ABSTRACT

PRCIS: Microvasculature dropout in the parapapillary choroidal layer was a more important biomarker of glaucomatous nerve fiber layer thinning when it presented with deep-layer microvasculature of the optic disc rather than when it presents by itself. PURPOSE: To characterize open angle glaucoma eyes with optic nerve head deep-layer microvasculature dropout (MvD-D) and parapapillary choroidal layer microvasculature dropout (MvD-P) and compare their retinal nerve fiber layer (RNFL) thinning rate. MATERIAL AND METHODS: This study included 122 open angle glaucoma eyes that underwent ≥5 serial spectral-domain optical coherence tomography scans during a mean follow-up of 5.4 years. Swept-source optical coherence tomography angiography was used to evaluate MvD-P and MvD-D. Subjects were classified into 3 groups according to the presence of MvD-P and MvD-D: (1) no dropout (n=37); (2) solely MvD-P (n=40), and (3) both MvD-P and MvD-D (n=45). The RNFL thinning rate was compared among the 3 groups, and the associated factors were assessed by Cox proportional hazard analysis. RESULTS: RNFL thinning rates were highest in the group with both MvD-P and MvD-D, followed by the group with solely MvD-P and finally by the no dropout group (-0.24 vs. -0.65 vs. -1.20 µm/y, P <0.001). Thinner central corneal thickness [hazard ratio (HR)0.990, P =0.003], presence of disc hemorrhage (HR=1.802, P =0.035), and coexistence of MvD-P and MvD-D (HR=2.941, P <0.001) were the factors associated with RNFL thinning. CONCLUSIONS: The coexistence of MvD-P and MvD-D was associated with faster RNFL thinning than MvD-P alone or no dropout, which suggested that observing the optic disc deep microvasculature along with parapapillary choroidal layer using Swept-source optical coherence tomography angiography may be clinically relevant in monitoring glaucoma progression.


Subject(s)
Glaucoma, Open-Angle , Optic Disk , Humans , Optic Disk/blood supply , Glaucoma, Open-Angle/complications , Glaucoma, Open-Angle/diagnosis , Visual Fields , Retinal Ganglion Cells , Intraocular Pressure , Tomography, Optical Coherence/methods , Microvessels , Nerve Fibers
20.
J Glaucoma ; 32(10): 833-840, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37523643

ABSTRACT

PRCIS: Reduced optic disc vessel density determined by swept-source optical coherence tomography angiography (SS-OCTA) was associated with visual field (VF) deterioration in glaucomatous eyes, which suggested that this parameter can be a potential biomarker that correlates well with functional deterioration. PURPOSE: The purpose of this study was to identify the association between optic disc perfusion evaluated by SS-OCTA and VF progression in primary open angle glaucoma (POAG) eyes. METHODS: A total of 266 POAG eyes of 266 patients (5.4 y of mean follow-up) were included. Optic nerve head SS-OCTA was performed to evaluate the optic disc vessel density (dVD), parapapillary choroidal vessel density (pcVD), choroidal microvascular dropout (cMvD), and optic disc microvascular dropout (dMvD). VF progression was defined using Early Manifest Glaucoma Trial criteria. Factors associated with VF worsening were assessed by Cox proportional hazard analysis. RESULTS: Eighty (30.1%) out of the 266 POAG eyes showed VF progression. The progression group showed a significantly higher proportion of disc hemorrhage, cMvD, and dMvD but lower dVD and pcVD than the stable group (all P <0.05). Considering the strong association between the parameters [dMvD vs. dVD ( r = -0.757, P =0.010], cMvD vs. pcVD ( r = -0.745, P =0.012), dMvD vs. cMvD ( r = 0.802, P <0.001], dVD vs. pcVD ( r = 0.862, P <0.001), CMvD vs. dVD ( r = -0.698, P =0.031), and dMvD vs. pcVD ( r = -0.688, P =0.034)], 6 models with different combinations of covariates compensating for multicollinearity were developed. Younger age, presence of disc hemorrhage, and lower dVD were consistently associated with progression in all models that included these parameters. CONCLUSIONS: Optic disc perfusion, represented as dVD, may be a useful biomarker that correlates well with functional deterioration in POAG eyes.


Subject(s)
Glaucoma, Open-Angle , Optic Disk , Humans , Optic Disk/blood supply , Visual Fields , Glaucoma, Open-Angle/complications , Glaucoma, Open-Angle/diagnosis , Tomography, Optical Coherence/methods , Visual Field Tests , Intraocular Pressure , Angiography , Perfusion , Biomarkers , Hemorrhage
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