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  • 1
    Online Resource
    Online Resource
    Role of Transient Receptor Potential Vanilloid 1 in Sonic Hedgehog-Dependent Taste Bud Differentiation
    MDPI AG ; 2022
    In:  Life Vol. 13, No. 1 ( 2022-12-27), p. 75-
    Details
    In: Life, MDPI AG, Vol. 13, No. 1 ( 2022-12-27), p. 75-
    Abstract: Taste bud cell differentiation is extremely important for taste sensation. Immature taste bud cells cannot function during taste perception transmission to the nerve. In this study, we investigated whether hedgehog signaling affected taste bud cell differentiation and whether transient receptor potential vanilloid 1 (TRPV1) played a key role in dry mouth. The induction of dry mouth due to salivary gland resection (SGR) was confirmed on the basis of reduced salivation and disrupted fungiform papillae. The expression of keratin 8 (K8) of taste bud cells, neurofilament (NF), sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (Gli1) around taste bud cells was downregulated; however, the expression of TRPV1, P2X purinoceptor 3 (P2X3), and hematopoietic stem cell factor (c-Kit) was upregulated at the NF ends in the dry mouth group. To investigate the effect of TRPV1 defect on dry mouth, we induced dry mouth in the TRPV-/- group. The K8, NF, and P2X3 expression patterns were the same in the TRPV1 wild-type and TRPV1-/- dry mouth groups. However, Shh and c-Kit expression decreased regardless of dry mouth in the case of TRPV1 deficiency. These results indicated that TRPV1 positively regulated proliferation during taste bud cell injury by blocking the Shh/Gli1 pathway. In addition, not only cell proliferation but also differentiation of taste bud cells could not be regulated under TRPV1-deficiency conditions. Thus, TRPV1 positively regulates taste bud cell innervation and differentiation; this finding could be valuable in the clinical treatment of dry mouth-related taste dysfunction.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life13010075
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662250-6
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  • 2
    Online Resource
    Online Resource
    MHY2245, a Sirtuin Inhibitor, Induces Cell Cycle Arrest and Apoptosis in HCT116 Human Colorectal Cancer Cells
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 3 ( 2022-01-29), p. 1590-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 3 ( 2022-01-29), p. 1590-
    Abstract: Sirtuins (SIRTs), which are nicotinamide adenine dinucleotide-dependent class III histone deacetylases, regulate cell division, survival, and senescence. Although sirtinol, a synthetic SIRT inhibitor, is known to exhibit antitumor effects, its mechanism of action is not well understood. Therefore, we aimed to assess the anticancer effects and underlying mechanism of MHY2245, a derivative of sirtinol, in HCT116 human colorectal cancer cells in vitro. Treatment with MHY2245 decreased SIRT1 activity and caused DNA damage, leading to the upregulation of p53 acetylation, and increased levels of p53, phosphorylation of H2A histone family member X, ataxia telangiectasia and Rad3-related kinase, checkpoint kinase 1 (Chk1), and Chk2. The level of the breast cancer type 1 susceptibility protein was also found to decrease. MHY2245 induced G2/M phase cell cycle arrest via the downregulation of cyclin B1, cell division cycle protein 2 (Cdc2), and Cdc25c. Further, MHY2245 induced HCT116 cell death via apoptosis, which was accompanied by internucleosomal DNA fragmentation, decreased B-cell lymphoma 2 (Bcl-2) levels, increased Bcl-2-asscociated X protein levels, cleavage of poly(ADP-ribose) polymerase, and activation of caspases -3, -8, and -9. Overall, MHY2245 induces cell cycle arrest, triggers apoptosis through caspase activation, and exhibits DNA damage response-associated anticancer effects.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23031590
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Nectin-4 as a Predictive Marker for Poor Prognosis of Endometrial Cancer with Mismatch Repair Impairment
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 10 ( 2023-05-22), p. 2865-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 10 ( 2023-05-22), p. 2865-
    Abstract: The adhesion molecule Nectin-4 is a new potential therapeutic target for different types of cancer; however, little is known about its diagnosis significance in endometrial cancer (EC). We found that Nectin-4 expression was significantly higher in EC tissues than in nonadjacent normal tissue. The area under the receiver operating characteristic curve value of 0.922 indicated good diagnostic accuracy for Nectin-4 expression in EC. Furthermore, Nectin-4 expression was associated with DNA mismatch repair (MMR) protein deficiency. Notably, the high Nectin-4 expression group of patients with MSH2/6-deficient EC had shorter progression-free survival than that of the low Nectin-4 expression group. The number of lymphovascular space invasion-positive patients in groups with MMR deficiency and high Nectin-4 expression was also increased compared with that in the low Nectin-4 expression group. Bioinformatics analysis revealed that alteration in Nectin-4 and MMR genes is associated with Nectin-4 expression in EC. To the best of our knowledge, this is the first study to show that Nectin-4 expression may be a potential biomarker for EC diagnosis and that high Nectin-4 expression in MMR-deficient patients with EC can predict short progression-free survival, thus providing clues to identify patients for adjuvant therapy.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15102865
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 4
    Online Resource
    Online Resource
    Anti-Inflammatory Effects of M-MSCs in DNCB-Induced Atopic Dermatitis Mice
    MDPI AG ; 2020
    In:  Biomedicines Vol. 8, No. 10 ( 2020-10-21), p. 439-
    Details
    In: Biomedicines, MDPI AG, Vol. 8, No. 10 ( 2020-10-21), p. 439-
    Abstract: Atopic dermatitis (AD) is an inflammatory skin disease caused by an imbalance between Th1 and Th2 cells. AD patients suffer from pruritus, excessive dryness, red or inflamed skin, and complications such as sleep disturbances and depression. Although there are currently many AD treatments available there are insufficient data on their long-term stability and comparative effects. Moreover, they have limitations due to various side effects. Multipotent mesenchymal stem cells (M-MSCs) might have potential for next-generation AD therapies. MSCs are capable of immune function regulation and local inflammatory response inhibition. M-MSCs, derived from human embryonic stem cells (hESC), additionally have a stable supply. In L507 antibody array, M-MSCs generally showed similar tendencies to bone marrow-derived mesenchymal stem cells (BM-MSCs), although the immunoregulatory function of M-MSCs seemed to be superior to BM-MSCs. Based on the characteristics of M-MSCs on immunoregulatory functions, we tested a M-MSC conditioned media concentrate (MCMC) in mice with AD lesions on their dorsal skin. MCMC significantly decreased RNA expression levels of inflammatory cytokines in the mouse dorsal skin. It also suppressed serum IgE levels. In addition, significant histopathologic alleviation was identified. In conclusion, secretions of M-MSCs have the potential to effectively improve AD-related inflammatory lesions. M-MSCs showed potential for use in next-generation AD treatment.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines8100439
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720867-9
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  • 5
    Online Resource
    Online Resource
    Differences in Interactions with a Conversational Agent
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 9 ( 2020-05-04), p. 3189-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 9 ( 2020-05-04), p. 3189-
    Abstract: Recent technological advances introduced conversational agents into homes. Many researchers have investigated how people utilize and perceive them. However, only a small number of studies have focused on how older adults interact with these agents. This study presents a 14-day user study of 19 participants who experienced a conversational agent in a real-life environment. We grouped them into two groups by age and compared their experiences. From a log study and semi-structured interviews, we identified several differences between the two groups. Compared to younger adults, older adults used the agent more. They used it primarily for listening to music and reported satisfaction with it. Younger adults mainly used utility skills like weather report checks and setting of alarms, which streamlined their daily lives. Moreover, older adults tended to view the agent as a companion, while younger adults saw it as a tool. Based on these empirical findings, we suggest that conversational agents should be designed with consideration of the different usage patterns and perceptions across age groups.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17093189
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 6
    Online Resource
    Online Resource
    Underweight Is Associated with a Higher Risk of Acute Pancreatitis in Type 2 Diabetes: A Nationwide Cohort Study
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 19 ( 2022-09-25), p. 5641-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 19 ( 2022-09-25), p. 5641-
    Abstract: Type 2 diabetes is known as a risk factor for acute pancreatitis, but the risk of acute pancreatitis according to glycemic status and body mass index (BMI) has remained unknown. Therefore, we aim to investigate the risk of acute pancreatitis according to BMI and glycemic status. We included 3,912,496 subjects from the Korean National Health Insurance System cohort who underwent the National Health Screening program in 2009. Each subject’s clinical course was examined through follow-ups until December 2018. BMI and glycemic status were each categorized into five groups. Hazard ratios (HRs) of acute pancreatitis according to BMI and glycemic status were calculated. The adjusted HRs of acute pancreatitis were the highest in the underweight group (BMI 〈 18.5) in all five glycemic status categories. The HR of acute pancreatitis in the underweight group increased as the glycemic status worsened, excluding the category of diabetes for more than five years (HR 1.381 for normal fasting glucose; 1.805 for impaired fasting glucose; 2.332 for new-onset diabetes; 4.51 for diabetes duration 〈 5 years; 4.135 for diabetes duration ≥5 years). We found that the risk of acute pancreatitis was further increased in the underweight group, depending on the status and duration of type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11195641
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 7
    Online Resource
    Online Resource
    The Effect of Hexanoyl Glycol Chitosan on the Proliferation of Human Mesenchymal Stem Cells
    MDPI AG ; 2018
    In:  Polymers Vol. 10, No. 8 ( 2018-07-30), p. 839-
    Details
    In: Polymers, MDPI AG, Vol. 10, No. 8 ( 2018-07-30), p. 839-
    Abstract: Adipose-derived mesenchymal stem cells (AD-MSCs) have been studied as desirable cell sources for regenerative medicine and therapeutic application. However, it has still remained a challenge to obtain enough adequate and healthy cells in large quantities. To overcome this limitation, various biomaterials have been used to promote expansion of MSCs in vitro. Recently, hexanoyl glycol chitosan (HGC) was introduced as a new biomaterial for various biomedical applications, in particular 3D cell culture, because of its biodegradability, biocompatibility, and other promising biofunctional properties. In this study, the effect of HGC on the proliferation of AD-MSCs was examined in vitro, and its synergistic effect with basic fibroblast growth factor (bFGF), which has been widely used to promote proliferation of cells, was evaluated. We found that the presence of HGC increased the proliferative capacity of AD-MSCs during long-term culture, even at low concentrations of bFGF. Furthermore, it suppressed the expression of senescence-related genes and improved the mitochondrial functionality. Taken all together, these findings suggest that the HGC demonstrate a potential for sustained growth of AD-MSCs in vitro.
    Type of Medium: Online Resource
    ISSN: 2073-4360
    URL: Article
    DOI: 10.3390/polym10080839
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2527146-5
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  • 8
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    Online Resource
    Uncertainty Analysis of Monthly Precipitation in GCMs Using Multiple Bias Correction Methods under Different RCPs
    MDPI AG ; 2020
    In:  Sustainability Vol. 12, No. 18 ( 2020-09-11), p. 7508-
    Details
    In: Sustainability, MDPI AG, Vol. 12, No. 18 ( 2020-09-11), p. 7508-
    Abstract: This study quantified the uncertainties in historical and future average monthly precipitation based on different bias correction methods, General Circulation Models (GCMs), Representative Concentration Pathways (RCPs), projection periods, and locations within the study area (i.e., the coastal and inland areas of South Korea). The GCMs were downscaled using deep learning, random forest, and nine quantile mapping bias correction methods for 22 gauge stations in South Korea. Data from the Korean Meteorology Administration (1970–2005) were used as the reference data in this study. Two statistical measures, the standard deviation and interquartile range, were used to quantify the uncertainties. The probability distribution density was used to assess the similarity/variation in rainfall distributions. For the historical period, the uncertainty in the selection of bias correction methods was greater than that in the selection of GCMs, whereas the opposite pattern was observed for the projection period. The projection period had the lowest level of uncertainty in the selection of RCP scenarios, and for the future, the uncertainly related to the time period was slightly lower than that for the other sources but was much greater than that for the RCP selection. In addition, it was clear that the level of uncertainty of inland areas is much lower than that of coastal areas. The uncertainty in the selection of the GCMs was slightly greater than that in the selection of the bias correction method. Therefore, the uncertainty in the selection of coastal areas was intermediate between the selection of bias correction methods and GCMs. This paper contributes to an improved understanding of the uncertainties in climate change projections arising from various sources.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su12187508
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518383-7
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  • 9
    Online Resource
    Online Resource
    Changes in Suicide Rate and Characteristics According to Age of Suicide Attempters before and after COVID-19
    MDPI AG ; 2022
    In:  Children Vol. 9, No. 2 ( 2022-01-25), p. 151-
    Details
    In: Children, MDPI AG, Vol. 9, No. 2 ( 2022-01-25), p. 151-
    Abstract: This study aims to identify age-related suicide-related factors and changes in suicide rate before and after the onset of the COVID-19 pandemic. Methods: From 2018 to 2020, the patients who presented to the ED of a university hospital with a suicide attempt were classified into adolescents (≤18 years), adults (19–65 years), and elderly ( 〉 65 years), and the visits were grouped into before and after COVID-19. Results: There were 853 visits before and 388 visits after COVID-19, and the results showed that the number of adolescent and adult suicide patients increased immediately after the pandemic, but the overall trend did not show a significant difference from before the pandemic. In the adolescents, the ratio of male patients increased, interpersonal and school-related motivations decreased, the poisoning and cutting methods of suicide were more common, and hospitalization admissions increased. Among the elderly, the ratio of female patients increased, the number of single patients and patients without previous psychiatric problems increased, the motives for physical illness and death of people around increased, the falling and hanging methods of suicide were more common, and hospitalization admissions and deaths increased. Conclusion: The impact of COVID-19 on suicide rates and suicide-related factors varies by age group. This finding requires different approaches and methods to suicide prevention based on age.
    Type of Medium: Online Resource
    ISSN: 2227-9067
    URL: Article
    DOI: 10.3390/children9020151
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2732685-8
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  • 10
    Online Resource
    Online Resource
    The Glutathione Derivative, GSH Monoethyl Ester, May Effectively Whiten Skin but GSH Does Not
    MDPI AG ; 2016
    In:  International Journal of Molecular Sciences Vol. 17, No. 5 ( 2016-04-27), p. 629-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 17, No. 5 ( 2016-04-27), p. 629-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms17050629
    Language: English
    Publisher: MDPI AG
    Publication Date: 2016
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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