Determination of adipogenesis stages of human umbilical cord-derived mesenchymal stem cells using three-dimensional label-free holotomography.

Adipogenesis involves complex changes in gene expression, morphology, and cytoskeletal organization. However, the quantitative analysis of live cell images to identify their stages through morphological markers is limited. Distinct adipogenesis markers on human umbilical cord-derived mesenchymal stem cells (UC-MSCs) were identified through holotomography, a label-free live cell imaging technique. In the MSC-to-preadipocyte transition, the nucleus-to-cytoplasm ratio (0.080 vs. 0.052) and lipid droplet (LD) refractive index variation decreased (0.149 % vs. 0.061 %), whereas the LD number (20 vs. 65) increased. This event was also accompanied by the downregulation and upregulation of THY1 and Preadipocyte Factor-1 (PREF-1), respectively. In the preadipocyte to immature adipocyte shift, cell sphericity (0.20 vs. 0.43) and LD number (65 vs. 200) surged, large LDs (>10 µm3) appeared, and the major axis of the cell was reduced (143.7 µm vs. 83.12 µm). These findings indicate features of preadipocyte and immature adipocyte stages, alongside the downregulation of PREF-1 and upregulation of Peroxisome Proliferator-Activated Receptor gamma (PPARγ). In adipocyte maturation, along with PPARγ and Fatty Acid-Binding Protein 4 upregulation, cell compactness (0.15 vs. 0.29) and sphericity (0.43 vs. 0.59) increased, and larger LDs (>30 µm3) formed, marking immature and mature adipocyte stages. The study highlights the distinct adipogenic morphological biomarkers of adipogenesis stages in UC-MSCs, providing potential applications in biomedical and clinical settings, such as fostering innovative medical strategies for treating metabolic disease.

Prevalence of mild behavioural impairment and its association with cognitive and functional impairment in normal cognition, mild cognitive impairment, and mild Alzheimer's dementia.

BACKGROUND: Mild behavioural impairment (MBI) is an emergent and persistent neuropsychiatric symptom (NPS) in subjects aged 50 and older who are at risk for cognitive decline. We examined the prevalence of MBI across the spectrum from cognitively normal (CN), mild cognitive impairment (MCI), to dementia, and further investigated the association between the MBI domain and cognitive and functional impairment. METHOD: MBI was assessed in 2337 elderly patients in the Alzheimer's Disease Neuroimaging Initiative database (mean age, 73.04 years; 52.8% male). Among the subjects, 868 (37.1%) had normal cognition, 1066 (45.6%) had MCI, and 403 (17.2%) had mild Alzheimer's dementia (AD). MBI was evaluated in accordance with the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment diagnostic criteria for MBI, utilising the Neuropsychiatric Inventory. We compared the prevalence of the MBI domain with CN using multinominal logistic regression analysis and further quantified the magnitude of the association between MCI/AD and the MBI domains by calculating the population attributable risk (PAR). We assessed the association between the MBI domains and cognitive and functional impairment using simultaneous linear regression analysis. RESULTS: The most common MBI domains in each diagnostic group were affective dysregulation followed by impulse dyscontrol, decreased motivation, social inappropriateness, and abnormal perception or thought content. The PARs for MBI domains in subjects with MCI or AD were respectively: 16.60% and 24.34% for affective dysregulation; 3.72% and 18.06% for impulse dyscontrol; 4.78% and 14.13% for decreased motivation, 1.91% and 2.29% for social inappropriateness; and 0.68% and 3.85% for abnormal perception or thought content. All MBI domains except for social inappropriateness were significantly associated with a higher 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale total score. All MBI domains were significantly associated with a higher Functional Activities Questionnaire total score. CONCLUSION: Our findings show that MBI is highly prevalent across subjects with CN, MCI, and AD and is associated with cognitive and functional decline. MBI could be a crucial clinical phenotype relevant to the risk of cognitive and functional impairment, and provides a useful dimension pertinent to diagnostic approaches.

Contactless Interface Using Exhaled Breath and Thermal Imaging.

A new type of interface using a conduction hot spot reflecting the user's intention is presented. Conventional methods using fingertips to generate conduction hot points cannot be applied to those who have difficulty using their hands or cold hands. In order to overcome this problem, an exhaling interaction using a hollow rod is proposed and extensively analyzed in this paper. A preliminary study on exhaling interaction demonstrated the possibility of the method. This paper is an attempt to develop and extend the concept and provide the necessary information for properly implementing the interaction method. We have repeatedly performed conduction hot-point-generation experiments on various materials that can replace walls or screens to make wide use of the proposed interfaces. Furthermore, a lot of experiments have been conducted in different seasons, considering that the surface temperature of objects also changes depending on the season. Based on the results of an extensive amount of experiments, we provide key observations on important factors such as material, season, and user condition, which should be considered for realizing contactless exhaling interfaces.

Lack of Acceptance of Digital Healthcare in the Medical Market: Addressing Old Problems Raised by Various Clinical Professionals and Developing Possible Solutions.

Various digital healthcare devices and apps, such as blood glucose meters, blood pressure monitors, and step-trackers are commonly used by patients; however, digital healthcare devices have not been widely accepted in the medical market as of yet. Despite the various legal and privacy issues involved in their use, the main reason for its poor acceptance is that users do not use such devices voluntarily and continuously. Digital healthcare devices generally do not provide valuable information to users except for tracking self-checked glucose or walking. To increase the use of these devices, users must first understand the health data produced in the context of their personal health, and the devices must be easy to use and integrated into everyday life. Thus, users need to know how to manage their own data. Medical staff must teach and encourage users to analyze and manage their patient-generated healthcare data, and users should be able to find medical values from these digital devices. Eventually, a single customized service that can comprehensively analyze various medical data to provide valuable customized services to users, and which can be linked to various heterogeneous digital healthcare devices based on the integration of various health data should be developed. Digital healthcare professionals should have detailed knowledge about a variety of digital healthcare devices and fully understand the advantages and disadvantages of digital healthcare to help patients understand and embrace the use of such devices.

Long-Term Safety and Efficacy of Extended Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Real-World Practice.

BACKGROUND: Extended dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is frequently used for high-risk patients in real-world practice. However, there are limited data about the long-term efficacy of extended DAPT after percutaneous coronary intervention (PCI).Methods and Results:This study investigated 1,470 patients who underwent PCI. The study population was divided into 2 groups based on DAPT duration: guideline-based DAPT (G-DAPT; DAPT ≤12 months after PCI; n=747) and extended DAPT (E-DAPT; DAPT >12 months after PCI; n=723). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as cardiac death, myocardial infarction (MI), repeat target vessel revascularization, or stroke. The median follow-up duration was 80.8 months (interquartile range 60.6-97.1 months). The incidence of MACCE was similar in the G-DAPT and E-DAPT groups (21.0% vs. 18.3%, respectively; P=0.111). However, the E-DAPT group had a lower incidence of non-fatal MI (hazard ratio [HR] 0.535; 95% confidence interval [CI] 0.329-0.869; P=0.011), and target lesion revascularization (HR 0.490; 95% CI 0.304-0.792; P=0.004), and stent thrombosis (HR 0.291; 95% CI 0.123-0.688; P=0.005). The incidence of bleeding complications, including major bleeding, was similar between the 2 groups (5.2% vs. 6.3%, respectively; P=0.471). CONCLUSIONS: Although E-DAPT after DES implantation was not associated with a reduced rate of MACCE, it was associated with a significantly lower incidence of non-fatal MI, TLR, and stent thrombosis.

Efficient Methods of Utilizing Multi-SBAS Corrections in Multi-GNSS Positioning.

Various combining methods have been proposed to utilize multi-satellite-based augmentation system (SBAS) correction to provide accurate position in the global navigation satellite system (GNSS) receiver. However, the proposed methods have not been objectively compared and analyzed, making it difficult to know which ones are effective for multi-GNSS positioning. This paper presents efficient methods of combining multi-SBAS corrections in multi-GNSS positioning by comparing three methods: correction domain integration, measurement domain integration, and position domain integration. The performance of the three methods were analyzed through a covariance analysis that was expanded to multi-GNSS and multi-SBAS. Then, the results were verified by experiments using real measurements and corrections. Furthermore, implementation issues, such as computational complexity, availability, and flexibility, are analyzed. As a result, three methods had the same precision, but different complexity, availability, and flexibility. These results will be important guidelines to design, implement, and analyze navigation systems based on multi-GNSS with multi-SBAS corrections.

The absence of Rab27a accelerates the degradation of Melanophilin.

Melanophilin (Mlph) forms an interaction with Rab27a and the actin-based motor protein MyosinVa (MyoVa) on mature melanosome membranes and the tripartite complex regulates melanosome transport in melanocytes. In this study, we found that Rab27a siRNA decreased Mlph and Rab27a protein levels, but Mlph mRNA levels were not changed. Other Rab27a siRNA sequences also showed the same results. When Rab27a siRNA was treated with melan-a melanocytes, Rab27a protein was decreased within 6 hours and Mlph protein was decreased within 24 hours. To determine whether the absence of Rab27a promotes Mlph degradation, we inhibited protein degradation by treatment with proteasome (MG132) and lysosomal enzyme (E64D and Pepstatin A) inhibitors in melan-a melanocytes. MG132 inhibited the degradation of Mlph, but E64D and Pepstatin A had no effect on Mlph. The absence of Rab27a enhanced ubiquitination of Mlph and induced proteasomal degradation. From these results, we concluded that Mlph interaction with Rab27a is important for Mlph stability and melanosome transport.

In vivo Change of Keratin-Bound Molecules in the Human Stratum Corneum following Exposure to Ultraviolet Radiation.

BACKGROUND/OBJECTIVES: Ultraviolet (UV) radiation damages the stratum corneum (SC) and disrupts the skin barrier. The damaged skin changes in the molecular composition of the SC, including its water content. However, it is difficult to examine the in vivo SC changes with existing methods, so those have not been well characterized. Therefore, we investigated in vivo changes of UV-induced SC damage using confocal Raman spectroscopy. METHOD: We irradiated the volar forearm of 10 subjects with 0.5, 1, and 1.5 minimal erythemal doses of UV radiation. Then, we examined erythema, the transepidermal water loss (TEWL), the water content, the natural moisturizing factor (NMF), and the lipids of the skin. RESULTS: After UV irradiation, erythema and TEWL of the skin were both increased. The bound water content of the SC was also increased following UV irradiation. The NMF of the SC revealed different tendencies. All free amino acids (FAAs) of the NMF were increased after UV irradiation, except proline. trans-urocanic acid, pyrrolidone carboxylic acid, lactate, and urea, which are NMF components produced by the subsequent catabolism of FAAs and sweat, were decreased after UV irradiation. The amount of ceramide in the SC was also decreased after UV exposure, while cholesterol was increased. CONCLUSIONS: The bound water content of the SC was increased by UV exposure along with increasing TEWL, several NMF components, and cholesterol. These in vivo results for UV-damaged SC obtained via Raman spectroscopy could be applied to research with regard to protecting the SC from UV radiation and treating UV-damaged SC.

Adenine attenuates lipopolysaccharide-induced inflammatory reactions.

A nucleobase adenine is a fundamental component of nucleic acids and adenine nucleotides. Various biological roles of adenine have been discovered. It is not produced from degradation of adenine nucleotides in mammals but produced mainly during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine have been supported in IgE-mediated allergic reactions, immunological functions of lymphocytes and dextran sodium sulfate-induced colitis. However adenine effects on Toll-like receptor 4 (TLR4)-mediated inflammation by lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not examined. Here we investigated anti-inflammatory roles of adenine in LPS-stimulated immune cells, including a macrophage cell line RAW264.7 and bone marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines TNF-α and IL-6 and inflammatory lipid mediators, prostaglandin E2 and leukotriene B4. Adenine impeded signaling pathways eliciting production of these inflammatory mediators. It suppressed IκB phosphorylation, nuclear translocation of nuclear factor κB (NF-κB), phosphorylation of Akt and mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production of TNF-α, IL-6 and IL-13 and also hindered phosphorylation of NF-κB and Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of TNF-α and IL-6 by peritoneal cells in mice. These results show that adenine attenuates the LPS-induced inflammatory reactions.

Cell cloning-on-the-spot by using an attachable silicone cylinder.

Cell cloning is a laboratory routine to isolate and keep particular properties of cultured cells. Transfected or other genetically modified cells can be selected by the traditional microbiological cloning. In addition, common laboratory cell lines are prone to genotypic drift during their continual culture, so that supplementary cloning steps are often required to maintain correct lineage phenotypes. Here, we designed a silicone-made attachable cloning cylinder, which facilitated an easy and bona fide cloning of interested cells. This silicone cylinder was easy to make, showed competent stickiness to laboratory plastics including culture dishes, and hence enabled secure isolation and culture for days of selected single cells, especially, on the spots of preceding cell-plating dishes under microscopic examination of visible cellular phenotypes. We tested the silicone cylinder in the monoclonal subcloning from a heterogeneous population of a breast cancer cell line, MDA-MB-231, and readily established independent MDA-MB-231 subclones showing different sublineage phenotypes.

Practical system for generating digital mixed reality video holograms.

We propose a practical system that can effectively mix the depth data of real and virtual objects by using a Z buffer and can quickly generate digital mixed reality video holograms by using multiple graphic processing units (GPUs). In an experiment, we verify that real objects and virtual objects can be merged naturally in free viewing angles, and the occlusion problem is well handled. Furthermore, we demonstrate that the proposed system can generate mixed reality video holograms at 7.6 frames per second. Finally, the system performance is objectively verified by users' subjective evaluations.

Fast generation of a high-quality computer-generated hologram using a scalable and flexible PC cluster.

In order to efficiently generate a high-quality computer-generated hologram (HQ-CGH), which requires that both a three-dimensional object image and its computer-generated hologram (CGH) are in high-definition resolution, we implement a fast CGH generation system using a scalable and flexible personal computer (PC) cluster. From experimental results obtained in generating a HQ-CGH with a CGH resolution of 1536×1536 and 2,155,898 light sources using a PC cluster comprising a server PC and nine client PCs, it is verified that the proposed system is approximately 4.7 times faster than a single PC with two high-performance GPUs.

A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent.

BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B) agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2) and microphthalmia-associated transcription factor (MITF) in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA) and cAMP response element-binding protein (CREB) activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders.

Factors associated with depression among elderly Koreans: the role of chronic illness, subjective health status, and cognitive impairment.

OBJECTIVES: The objective of this cross-sectional study was to investigate the relationship between depression in elderly individuals and chronic illness, subjective health status, and cognitive impairment. METHOD: This study used the dataset of the Survey of Living Conditions and Welfare Needs of Korean Older Persons, which was conducted by the Korea Institute for Health and Social Affairs in 2011. Participants (n = 10,674) were randomly selected from a pool of individuals aged 65 years and older. Elderly depression was evaluated by the short version of the Geriatric Depression Scale. Multivariate logistic regression was used to investigate factors associated with depression in terms of their sociodemographic and health-related characteristics. RESULTS: Our results revealed that chronic illness, subjective health status, and cognitive impairment were significant factors associated with depression. In particular, subjective health status showed the highest odds ratio (OR) (OR for bad subjective health status = 4.290, P < 0.001), followed by chronic illness (OR for three or more chronic illnesses = 1.403, P < 0.01) and cognitive impairment (OR = 1.347, P < 0.001) in the final model. Interestingly, the significant association between chronic illness and depression was attenuated (OR for three or more chronic illnesses = 1.403, P = 0.01) or even disappeared (OR for two chronic illnesses = 1.138, P = 0.274; OR for one chronic illnesses = 0.999, P = 0.996) after adjustment for subjective health status in the final model; this may be attributable to the close relationship among the variables studied: chronic illness, subjective health status, and depression. CONCLUSIONS: Development and implementation of prevention strategies, including management of chronic illness, individual's perception of health status, and cognitive impairment, could possibly reduce the impact of depression.

PMA synergistically enhances apicularen A-induced cytotoxicity by disrupting microtubule networks in HeLa cells.

BACKGROUND: Combination therapy is key to improving cancer treatment efficacy. Phorbol 12-myristate 13-acetate (PMA), a well-known PKC activator, increases the cytotoxicity of several anticancer drugs. Apicularen A induces cytotoxicity in tumor cells through disrupting microtubule networks by tubulin down-regulation. In this study, we examined whether PMA increases apicularen A-induced cytotoxicity in HeLa cells. METHODS: Cell viability was examined by thiazolyl blue tetrazolium (MTT) assays. To investigate apoptotic potential of apicularen A, DNA fragmentation assays were performed followed by extracting genomic DNA, and caspase-3 activity assays were performed by fluorescence assays using fluorogenic substrate. The cell cycle distribution induced by combination with PMA and apicularen A was examined by flow cytometry after staining with propidium iodide (PI). The expression levels of target proteins were measured by Western blotting analysis using specific antibodies, and α-tubulin mRNA levels were assessed by reverse transcription polymerase chain reaction (RT-PCR). To examine the effect of combination of PMA and apicularen A on the microtubule architecture, α-tubulin protein and nuclei were visualized by immunofluorescence staining using an anti-α-tubulin antibody and PI, respectively. RESULTS: We found that apicularen A induced caspase-dependent apoptosis in HeLa cells. PMA synergistically increased cytotoxicity and apoptotic sub-G1 population induced by apicularen A. These effects were completely blocked by the PKC inhibitors Ro31-8220 and Go6983, while caspase inhibition by Z-VAD-fmk did not prevent cytotoxicity. RNA interference using siRNA against PKCα, but not PKCß and PKCγ, inhibited cytotoxicity induced by combination PMA and apicularen A. PMA increased the apicularen A-induced disruption of microtubule networks by further decreasing α- and ß-tubulin protein levels in a PKC-dependent manner. CONCLUSIONS: These results suggest that the synergy between PMA and apicularen A is involved by PKCα activation and microtubule disruption, and that may inform the development of novel approaches to treat cancer.

Docosahexaenoic acid-induced apoptosis is mediated by activation of mitogen-activated protein kinases in human cancer cells.

BACKGROUND: The role of omega-3 polyunsaturated fatty acids (ω3-PUFAs) in cancer prevention has been demonstrated; however, the exact molecular mechanisms underlying the anticancer activity of ω3-PUFAs are not fully understood. Here, we investigated the relationship between the anticancer action of a specific ω3-PUFA docosahexaenoic acid (DHA), and the conventional mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK) and p38 whose dysregulation has been implicated in human cancers. METHODS: MTT assays were carried out to determine cell viability of cancer cell lines (PA-1, H1299, D54MG and SiHa) from different origins. Apoptosis was confirmed by TUNEL staining, DNA fragmentation analysis and caspase activity assays. Activities of the conventional MAPKs were monitored by their phosphorylation levels using immunoblotting and immunocytochemistry analysis. Reactive oxygen species (ROS) production was measured by flow cytometry and microscopy using fluorescent probes for general ROS and mitochondrial superoxide. RESULTS: DHA treatment decreased cell viability and induced apoptotic cell death in all four studied cell lines. DHA-induced apoptosis was coupled to the activation of the conventional MAPKs, and knockdown of ERK/JNK/p38 by small interfering RNAs reduced the apoptosis induced by DHA, indicating that the pro-apoptotic effect of DHA is mediated by MAPKs activation. Further study revealed that the DHA-induced MAPKs activation and apoptosis was associated with mitochondrial ROS overproduction and malfunction, and that ROS inhibition remarkably reversed these effects of DHA. CONCLUSION: Together, these results indicate that DHA-induced MAPKs activation is dependent on its capacity to provoke mitochondrial ROS generation, and accounts for its cytotoxic effect in human cancer cells.

Predictors of suicidal ideation in older individuals receiving home-care services.

OBJECTIVES: Despite the importance of tending to older individuals who are vulnerable to suicide, little is known about suicidal ideation in the portion of this population receiving home-care services in Asian countries. The objective of this cross-sectional study was to examine predictors of suicidal ideation in older individuals using home-care service. METHOD: Participants were randomly selected from the individuals 50 years old and over using home-care services across Jeollabuk-do Province, Korea. A total of 697 subjects participated in this study. Each participant completed the short version of the Geriatric Depression Scale, the Scale for Suicidal Ideation, the Multidimensional Scale of Perceived Social Support, and the World Health Organization Disability Assessment Schedule II. RESULTS: Hierarchical regression analyses revealed that depression, perceived social support, and disability were significant predictors of suicidal ideation, whereas the roles of subjective health status and fish consumption remained ambiguous in this regard. In terms of social support, we also found that less perceived social support from family members was related to higher levels of suicidal ideation. The associations between various categories of disability and suicidal ideation disappeared after controlling for depression. Our investigation of the mediating effect of depression on the relationship between disability and suicidal ideation revealed that depression was either a complete (disability related to cognition, self-care, getting along with others, and life activities) or partial (disability related to participation) mediator. CONCLUSIONS: Preventive strategies focusing on depression, social support, and disability should be emphasized during encounters with older people receiving home-care services.

Elder Abuse in Association with Depression and Suicidal Ideation among Community-Dwelling Elderly in Korea.

There has been limited research on the association between elder abuse and depression, as well as elder abuse and suicidal ideation concurrently. Therefore, the present study aimed to investigate this association using the dataset from a nationally representative elderly sample in Korea. This study analyzed the dataset from the 2020 National Survey of Older Koreans. Elderly participants (aged over 65 years, n=9920) were included. Multivariate regression analysis was utilized to explore the risk factors associated with depression and suicidal ideation in the context of elder abuse. In this study, 5.1% of the elderly reported having elder abuse in the past year, while 12.8% and 1.9% reported having depression and suicidal ideation, respectively. In addition, among the elderly with depression, 8.4% had experienced elder abuse, while among those reporting suicidal ideation, 17.6% had suffered from elder abuse. Multiple logistic regression revealed that elder abuse is independently associated with both depression [odds ratio (OR) for elder abuse=1.642] and suicidal ideation (OR for elder abuse=3.237). Besides elder abuse, poor subjective health status and poor social support were linked to higher risk of depression and suicidal ideation. Our findings revealed that elder abuse represented a substantial risk factor associated with both depression and suicidal ideation. Implementing preventive interventions to address these risk factors could have significant implications for public mental health.