Organoids show great potential in clinical translational research owing to their intriguing properties to represent a near physiological model for native tissues. However, the dependency of organoid generation on the use of poorly defined matrices has hampered their clinical application. Current organoid culture systems mostly reply on biochemical signals provided by medium compositions and cell-cell interactions to control growth. Recent studies have highlighted the importance of the extracellular matrix (ECM) composition, cell-ECM interactions, and mechanical signals for organoid expansion and differentiation. Thus, several hydrogel systems prepared using natural or synthetic-based materials have been designed to recreate the stem cell niche in vitro, providing biochemical, biophysical, and mechanical signals. In this review, we discuss how recapitulating multiple aspects of the tissue-specific environment through designing and applying matrices could contribute to accelerating the translation of organoid technology from the laboratory to therapeutic and pharmaceutical applications.

Excessive activation of microglia causes the continuous production of neurotoxic mediators, which further causes neuron degeneration. Therefore, inhibition of microglial activation is a possible target for the treatment of neurodegenerative disorders. Balanophonin, a natural neolignoid from Firmiana simplex, has been reported to have anti-inflammatory and anti-cancer effects. In this study, we aimed to evaluate the anti-neuroinflammatory effects and mechanism of balanophonin in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. BV2 microglia cells were stimulated with LPS in the presence or absence of balanophonin. The results indicated that balanophonin reduced not only the LPS-mediated TLR4 activation but also the production of inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), in BV2 cells. Balanophonin also inhibited LPS-induced inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) protein expression and mitogen activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 MAPK. Interestingly, it also inhibited neuronal cell death resulting from LPS-activated microglia by regulating cleaved caspase-3 and poly ADP ribose polymerase (PARP) cleavage in N2a cells. In conclusion, our data indicated that balanophonin may delay the progression of neuronal cell death by inhibiting microglial activation.
Apoptosis ; Caspase 3 ; Cell Death* ; Cyclooxygenase 2 ; Dinoprostone ; JNK Mitogen-Activated Protein Kinases ; Microglia ; Mitogen-Activated Protein Kinases ; Necrosis ; Nerve Degeneration ; Neurodegenerative Diseases ; Neurons* ; Neuroprotection ; Nitric Oxide ; Nitric Oxide Synthase Type II ; p38 Mitogen-Activated Protein Kinases ; Phosphotransferases ; Poly(ADP-ribose) Polymerases

Objective To investigate the effects of an ar?turmerone derivative(ATD)on the proliferation and apoptosis of A375 human melanoma cells. Methods Both A375 cells and human skin fibroblasts (HSFs) were cultured with different concentrations(5, 10, 20, 40 and 80μmol/L)of ATD, vincristine and ar?turmerone, separately, for 48 hours in vitro. Subsequently, cell counting kit?8 (CCK?8) was used to evaluate cell proliferation, inverted microscopy to observe cell morphology after acridine orange/ethidium bromide (AO/EB) staining, and a colorimetric method to estimate caspase?3 activity. DNA fragmentation assay and flow cytometry were performed to assess cell apoptosis, and flow cytometry was conducted to analyze cell cycle. Results ATD, vincristine and Ar?turmerone all inhibited the proliferation of A375 cells in a dose?dependent manner(ATD:R2=0.99, F=340.96, P<0.05;vincristine:R2=0.99, F=349.19, P<0.05;ar?turmerone:R2=0.89, F=25.41, P<0.05). The fifty percent inhibitory concentra?tions(IC50s)of ATD, vincristine and ar?turmerone against A375 cells were 15.96 ± 0.02μmol/L, 77.00 ± 0.04μmol/L and 356.95 ± 0.01μmol/L respectively. When the drug concentrations were 5 and 10μmol/L, the proliferation of HSFs was inhibited by 8%± 0.06%and 25%± 0.02%respectively by ATD, by 49%± 0.09%and 34%± 0.07%respectively by ar?turmerone, and by 33%± 0.04%and 29%± 0.08%respectively by vincristine, and the proliferation of A375 cells was inhibited by 26%± 0.06%and 39%± 0.02%respectively by ATD, by 6%± 0.09%and 10%± 0.07%respectively by ar?turmerone, and by 8% ± 0.04% and 17% ± 0.08% respectively by vincristine, with the inhibitory effects of the three drugs being significantly different from that of dimethyl sulfoxide(all P<0.05). ATD showed stronger inhibitory effects on the proliferation of A375 cells, but weaker cytotoxic effects on HSFs compared with ar?turmerone and vincristine(all P<0.05). Meanwhile, ATD, vincristine and ar?turmerone all induced the apoptosis of A375 cells(P<0.05), and caspase?3 activity increased with the increase in drug concentrations(ATD:R2=0.98, F=162.30, P<0.05;vincristine:R2=0.96, F=94.39, P<0.05;ar?turmerone:R2=0.95, F=57.35, P<0.05). The effect of ATD on caspase?3 activity was strongest, followed by that of vincristine and ar?turmerone. As flow cytometry showed, all the three drugs induced cell apoptosis to different degrees, and ATD showed a relatively strong effect on cell apoptosis, especially late apoptosis, compared with the other two drugs. In the ATD group, the number of A375 cells in G1 phase gradually increased, while that in G2 phase and S phase significantly decreased with the increase in drug concentrations. Conclusions ATD exhibited proliferation?inhibiting and apoptosis?inducing effects on A375 cells, and the effects were stronger than those of vincristine and ar?turmerone. It is quite possible that ATD affects cell proliferation and differentiation by activating caspase?3 and arresting cell cycle in the G1 phase.

Objectives: The aim of this study was to investigate temperament and character associated with resilience in patients with bipolar disorder (BD). Methods: A total of 55 outpatients diagnosed with BD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and 55 healthy controls matched by age and sex with the BD group were recruited.All participants completed the Connor-Davidson Resilience Scale (CD-RISC) and Temperament and Character Inventory (TCI). Multiple linear regression analysis was performed by controlling for age, length of education, age of onset, number of depressive episodes, and number of hospitalizations to determine factors related to resilience. In addition, multiple regression analysis was performed using the interaction term to investigate whether temperament and character associated with resilience differed between the two groups. Results: Patients with BD showed higher harm avoidance (p<0.001) and lower self-directedness (p<0.001) among the TCI dimensions compared to the control group. In multiple regression analysis, harm avoidance (β=-0.274, p=0.025) and self-directedness (β=0.431, p=0.002) were associated with resilience in patients with BD, while harm avoidance (β=-0.411, p=0.008), persistence (β=0.244, p=0.031), and cooperativeness (β=0.264, p=0.037) were associated with resilience in the control group. Self-directedness had a different relationship with resilience between the two groups (β=0.212, p=0.001). Conclusions The findings suggest that BD patients’ particular temperament and character are associated with resilience.Furthermore, temperament and character related to resilience differed between the BD group and the control group.

Objectives: ：Suicide is a global social problem. Social burden caused by suicide is gradually increasing. Various efforts have been made to prevent suicide. Lifestyle changes to western style, especially diet changes, have increased the risk for suicide. Therefore, in this study, we discussed diet as an adjuvant treatment for suicide. Methods: ：In this review, we summarized the biochemical mechanism of suicide, and diet as a risk factor for suicide and diet as a protective factor through a web search. Results: ：In this study, biochemical mechanisms for suicide were reviewed and diet as a risk factor and diet as a protective factor for suicide were investigated. It was confirmed that neurotoxic effects such as oxidative stress and inflammation in the neural system could increase the risk of suicide. Based on results of previous stud-ies on the relationship between suicide and diet, it was found that heavy use of alcohol, coffee, carbonated soft drink, and fast food were risk factors for suicide. Protective factors for suicide included antioxidants such as vitamin C, carotene, and anti-inflammatory agents such as omega-3 fatty acids found in seafood in large amounts. Conclusions ：The only treatment for suicide is prevention. In this context, effectiveness, accessibility, and safety are important for preventing for suicide. Antioxidants and anti-inflammatory agents that are relatively safe and readily available to the public could be effective adjuvant treatments to decrease the risk of suicide. In addition, it is necessary to educate the public on reducing diets that could increase the risk of suicide

Objectives: Following the coronavirus disease 2019 (COVID-19) pandemic, adolescents have experienced decreased physical activity and a decline in mental health. This study analyzed the association between changes in depressed mood after the COVID-19 pandemic and physical activity among adolescents. Methods: The analysis was based on the results of the 17th Youth Health Behavior Online Survey conducted in 2021, which included 54848 middle and high school students in South Korea. Information on physical activity included low-intensity physical activity lasting >60 min/day, high-intensity physical activity, and strength training exercises. A logistic regression analysis was performed to evaluate the association between physical activity and changes in depression after the COVID-19 pandemic. Results: After adjusting for sociodemographic characteristics and previous depression, adolescents who performed strength training exercises more than once per week had a 0.95-fold lower risk (odds ratio [OR]=0.948, 95% confidence interval [CI]=0.905–0.994, p= 0.027) of increasing depression after the COVID-19 pandemic, while the risk of decreasing depression increased by 1.22-fold (OR=1.215, 95% CI=1.131–1.305, p<0.001). The results were not significant for low-intensity physical activity for >60 min/day and high-intensity physical activity. Conclusion Strength-training exercises are significantly associated with the prevention of depression among adolescents following the COVID-19 pandemic.

Objective: The suicide rate in Korea was the highest among countries in the Organisation for Economic Co-operation and Development in 2019. In a previous study, higher intake of vegetables and fruits was associated with a lower risk of suicidal ideation, and carotene-rich fruits and vegetables lowered the risk of depression. This study aimed to examine the direct relationship between carotene intake and suicidal ideation, adjusting for the effect on depression. Methods: This study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2012, 2013, and 2015. Carotene intake was assessed through a food intake frequency survey with a 24-hour recall. Suicidal ideation and depression were assessed using the mental health section of the KNHANES. We applied logistic regression to assess the relationship between carotene intake and suicidal ideation, adjusting for potential confounders. Results: A total of 5,480 females aged 19–64 years were included in this study. Carotene intake was significantly lower in the suicidal ideation group (3,034.5±1,756.4 μg/day) than in the nonsuicidal ideation group (3,225.4±1,795.1 μg/day) (p=0.015). We found a significant inverse association between carotene intake and the risk of suicidal ideation after adjusting for potential confounders (odds ratio=0.934, 95% confidence interval=0.873–0.999). Conclusion These results suggest that carotene intake may be inversely associated with the risk of suicidal ideation. Our findings may inform the development of new nutritional interventions to prevent increases in the risk of suicide worldwide.

Objectives: ：Among the various risk factors for suicide, geographic factors have different effects on males and females. This study aimed to identify differences between genders in spatiotemporal dependence and spatiotemporal patterns of suicide mortality over the preceding decade. Methods: ：This research analyzed the age-adjusted suicide mortality rate per 100,000 population, spanning from 2012 to 2021, for intentional suicides across each administrative district (229 Si, Gun, Gu) in Korea. Data were sourced from the National Statistical Office of the Korean Statistical Information Service. The Moran’s I in-dex for spatial autocorrelation of the suicide mortality rates was computed. An emerging hot spot analysis was conducted to examine the community-level spatiotemporal distribution patterns, thus providing insight into the re-gional clustering characteristics that reflect the temporal-spatial clusters of suicide mortality rates. Results: ：TIn males, the Moran’s I indices were almost above 0 (p-value<0.05) for most years, indicating sig-nificant spatial autocorrelation. Conversely, no significant regional clustering was observed among females dur-ing the same period. The emerging hot spot analysis, focusing on the temporal trends in the spatial distributionof male suicide mortality rates from 2012 to 2021, identified two distinct time series patterns and a total of 12 hot spot areas: seven new spots and five sporadic spots. Conclusions ：This study is the first to intuitively demonstrate the disparities in spatiotemporal dependencies and patterns of suicide mortality rates in Korea between genders. The findings highlight the necessity for tailoredsuicide prevention strategies that are sensitive to gender differences.

Objectives: Eveningness predominates in adolescence. Morningness has been reported to be associated with mental toughness via resilience. Morningness could be related to healthy sleep habits and a good personality. Methods: Sleep-related behaviors, such as weekend oversleep, social jetlag, and daytime sunlight exposure between 10:00 and 15:00, were evaluated using sleep-related questionnaires. Morningness-eveningness questionnaire, insomnia severity index, Epworth sleepiness scale, hospital anxiety and depression scale and defense style questionnaire were used. This study includes 1,610 high school students. Results: Multiple linear regression analysis revealed that morningness is predicted by male sex (β=0.115, t=4.769, p<0.001) and greater adaptive (β=0.092, t=3.506, p<0.001) and self-suppressive defense styles (β=0.072, t=2.192, p=0.029) and lesser immature defense styles (β=-0.163, t=-4.782, p<0.001) after controlling for age, sleep quality, depression, anxiety. Morningness is also predicted by greater sublimation (β=0.09, t=3.541, p<0.001) and reaction formation (β=0.112, t=4.488, p<0.001) and lesser consumption (β=-0.062, t=-2.501, p=0.012), passive aggression (β=-0.101, t=-3.747, p<0.001) and withdrawal (β=-0.084, t=-2.955, p=0.003), and male sex (β=0.117, t=4.896, p<0.001) after controlling for age, sleep quality, depression, and anxiety. Conclusion Morniness in adolescence may be related to a positive personality. Promoting morningness might be related to healthy development in personality.

Objectives: ：Among the various risk factors for suicide, geographic factors have different effects on males and females. This study aimed to identify differences between genders in spatiotemporal dependence and spatiotemporal patterns of suicide mortality over the preceding decade. Methods: ：This research analyzed the age-adjusted suicide mortality rate per 100,000 population, spanning from 2012 to 2021, for intentional suicides across each administrative district (229 Si, Gun, Gu) in Korea. Data were sourced from the National Statistical Office of the Korean Statistical Information Service. The Moran’s I in-dex for spatial autocorrelation of the suicide mortality rates was computed. An emerging hot spot analysis was conducted to examine the community-level spatiotemporal distribution patterns, thus providing insight into the re-gional clustering characteristics that reflect the temporal-spatial clusters of suicide mortality rates. Results: ：TIn males, the Moran’s I indices were almost above 0 (p-value<0.05) for most years, indicating sig-nificant spatial autocorrelation. Conversely, no significant regional clustering was observed among females dur-ing the same period. The emerging hot spot analysis, focusing on the temporal trends in the spatial distributionof male suicide mortality rates from 2012 to 2021, identified two distinct time series patterns and a total of 12 hot spot areas: seven new spots and five sporadic spots. Conclusions ：This study is the first to intuitively demonstrate the disparities in spatiotemporal dependencies and patterns of suicide mortality rates in Korea between genders. The findings highlight the necessity for tailoredsuicide prevention strategies that are sensitive to gender differences.