Exploring a multimodal approach for utilizing digital biomarkers for childhood mental health screening.

Background: Depression and anxiety are prevalent mental health concerns among children and adolescents. The application of conventional assessment methods, such as survey questionnaires to children, may lead to self-reporting issues. Digital biomarkers provide extensive data, reducing bias in mental health self-reporting, and significantly influence patient screening. Our primary objectives were to accurately assess children's mental health and to investigate the feasibility of using various digital biomarkers. Methods: This study included a total of 54 boys and girls aged between 7 to 11 years. Each participant's mental state was assessed using the Depression, Anxiety, and Stress Scale. Subsequently, the subjects participated in digital biomarker collection tasks. Heart rate variability (HRV) data were collected using a camera sensor. Eye-tracking data were collected through tasks displaying emotion-face stimuli. Voice data were obtained by recording the participants' voices while they engaged in free speech and description tasks. Results: Depressive symptoms were positively correlated with low frequency (LF, 0.04-0.15 Hz of HRV) in HRV and negatively associated with eye-tracking variables. Anxiety symptoms had a negative correlation with high frequency (HF, 0.15-0.40 Hz of HRV) in HRV and a positive association with LF/HF. Regarding stress, eye-tracking variables indicated a positive correlation, while pNN50, which represents the proportion of NN50 (the number of pairs of successive R-R intervals differing by more than 50 milliseconds) divided by the total number of NN (R-R) intervals, exhibited a negative association. Variables identified for childhood depression included LF and the total time spent looking at a sad face. Those variables recognized for anxiety were LF/HF, heart rate (HR), and pNN50. For childhood stress, HF, LF, and Jitter showed different correlation patterns between the two grade groups. Discussion: We examined the potential of multimodal biomarkers in children, identifying features linked to childhood depression, particularly LF and the Sad.TF:time. Anxiety was most effectively explained by HRV features. To explore reasons for non-replication of previous studies, we categorized participants by elementary school grades into lower grades (1st, 2nd, 3rd) and upper grades (4th, 5th, 6th). Conclusion: This study confirmed the potential use of multimodal digital biomarkers for children's mental health screening, serving as foundational research.

The Effectiveness of a Digital App for Reduction of Clinical Symptoms in Individuals With Panic Disorder: Randomized Controlled Trial.

BACKGROUND: Panic disorder is a common and important disease in clinical practice that decreases individual productivity and increases health care use. Treatments comprise medication and cognitive behavioral therapy. However, adverse medication effects and poor treatment compliance mean new therapeutic models are needed. OBJECTIVE: We hypothesized that digital therapy for panic disorder may improve panic disorder symptoms and that treatment response would be associated with brain activity changes assessed with functional near-infrared spectroscopy (fNIRS). METHODS: Individuals (n=50) with a history of panic attacks were recruited. Symptoms were assessed before and after the use of an app for panic disorder, which in this study was a smartphone-based app for treating the clinical symptoms of panic disorder, panic symptoms, depressive symptoms, and anxiety. The hemodynamics in the frontal cortex during the resting state were measured via fNIRS. The app had 4 parts: diary, education, quest, and serious games. The study trial was approved by the institutional review board of Chung-Ang University Hospital (1041078-202112-HR-349-01) and written informed consent was obtained from all participants. RESULTS: The number of participants with improved panic symptoms in the app use group (20/25, 80%) was greater than that in the control group (6/21, 29%; χ21=12.3; P=.005). During treatment, the improvement in the Panic Disorder Severity Scale (PDSS) score in the app use group was greater than that in the control group (F1,44=7.03; P=.01). In the app use group, the total PDSS score declined by 42.5% (mean score 14.3, SD 6.5 at baseline and mean score 7.2, SD 3.6 after the intervention), whereas the PDSS score declined by 14.6% in the control group (mean score 12.4, SD 5.2 at baseline and mean score 9.8, SD 7.9 after the intervention). There were no significant differences in accumulated oxygenated hemoglobin (accHbO2) at baseline between the app use and control groups. During treatment, the reduction in accHbO2 in the right ventrolateral prefrontal cortex (VLPFC; F1,44=8.22; P=.006) and the right orbitofrontal cortex (OFC; F1,44=8.88; P=.005) was greater in the app use than the control group. CONCLUSIONS: Apps for panic disorder should effectively reduce symptoms and VLPFC and OFC brain activity in patients with panic disorder. The improvement of panic disorder symptoms was positively correlated with decreased VLPFC and OFC brain activity in the resting state. TRIAL REGISTRATION: Clinical Research Information Service KCT0007280; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=21448.

Protective Effects of Red Ginseng Against Tacrine-Induced Hepatotoxicity: An Integrated Approach with Network Pharmacology and Experimental Validation.

Introduction: Tacrine, an FDA-approved acetylcholinesterase inhibitor, has shown efficacy in treating Alzheimer's disease, but its clinical use is limited by hepatotoxicity. This study investigates the protective effects of red ginseng against tacrine-induced hepatotoxicity, focusing on oxidative stress. Methods: A network depicting the interaction between compounds and targets was constructed for RG. Effect of RG was determined by MTT and FACS analysis with cells stained by rhodamine 123. Proteins were extracted and subjected to immunoblotting for apoptosis-related proteins. Results: The outcomes of the network analysis revealed a significant association, with 20 out of 82 identified primary RG targets aligning with those involved in oxidative liver damage including notable interactions within the AMPK pathway. in vitro experiments showed that RG, particularly at 1000µg/mL, mitigated tacrine-induced apoptosis and mitochondrial damage, while activating the LKB1-mediated AMPK pathway and Hippo-Yap signaling. In mice, RG also protected the liver injury induced by tacrine, as similar protective effects to silymarin, a well-known drug for liver toxicity protection. Discussion: Our study reveals the potential of RG in mitigating tacrine-induced hepatotoxicity, suggesting the administration of natural products like RG to reduce toxicity in Alzheimer's disease treatment.

Antioxidant Efficacy of Hwangryunhaedok-tang through Nrf2 and AMPK Signaling Pathway against Neurological Disorders In Vivo and In Vitro.

Alzheimer's disease (AD) is a representative cause of dementia and is caused by neuronal loss, leading to the accumulation of aberrant neuritic plaques and the formation of neurofibrillary tangles. Oxidative stress is involved in the impaired clearance of amyloid beta (Aß), and Aß-induced oxidative stress causes AD by inducing the formation of neurofibrillary tangles. Hwangryunhaedok-tang (HHT, Kracie K-09®), a traditional herbal medicine prescription, has shown therapeutic effects on various diseases. However, the studies of HHT as a potential treatment for AD are insufficient. Therefore, our study identified the neurological effects and mechanisms of HHT and its key bioactive compounds against Alzheimer's disease in vivo and in vitro. In a 5xFAD mouse model, our study confirmed that HHT attenuated cognitive impairments in the Morris water maze (MWM) test and passive avoidance (PA) test. In addition, the prevention of neuron impairment, reduction in the protein levels of Aß, and inhibition of cell apoptosis were confirmed with brain tissue staining. In HT-22 cells, HHT attenuates tBHP-induced cytotoxicity, ROS generation, and mitochondrial dysfunction. It was verified that HHT exerts a neuroprotective effect by activating signaling pathways interacting with Nrf2, such as MAPK/ERK, PI3K/Akt, and LKB1/AMPK. Among the components, baicalein, a bioavailable compound of HHT, exhibited neuroprotective properties and activated the Akt, AMPK, and Nrf2/HO-1 pathways. Our findings indicate a mechanism for HHT and its major bioavailable compounds to treat and prevent AD and suggest its potential.

Forsythiaside A Activates AMP-Activated Protein Kinase and Regulates Oxidative Stress via Nrf2 Signaling.

Forsythiaside A (FA) is an active constituent isolated from Forsythia suspensa, a beneficial herb used in traditional medicine known for its antioxidant and anti-inflammatory properties. Although various studies have suggested that FA has the protective effects, its impacts on arachidonic acid (AA) plus iron in vitro models and carbon tetrachloride (CCl4)-induced mouse liver damage in vivo have not been explored. In this study, HepG2 cells were subjected to AA + iron treatment to induce apoptosis and mitochondrial impairment and determine the molecular mechanisms. FA exhibited protective effects by inhibiting cell damage and reactive oxygen species (ROS) production induced by AA + iron, as assessed via immunoblot and flow cytometry analyses. Further molecular investigations revealed that FA resulted in the activation of extracellular-signal-related protein kinase (ERK), which subsequently triggered the activation of AMP-activated protein kinase (AMPK), a critical regulator of cellular oxidative stress. Additionally, FA modulated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which is a significant antioxidant transcription factor regulated by the AMPK pathway. For in vivo studies, mice were orally administered FA and then subjected to induction of CCl4-based hepatotoxicity. The protective effect of FA was confirmed via blood biochemistry and immunohistochemical analyses. In conclusion, our findings demonstrated the protective effects of FA against oxidative stress both in vitro and in vivo, thus indicating that FA is a potential candidate for liver protection. Our study sheds light on the mechanistic pathways involved in the antioxidant effects of FA, highlighting the hepatoprotective potential of naturally occurring compounds in traditional herbs, such as FA.

Attention Circuits Mediate the Connection between Emotional Experience and Expression within the Emotional Circuit.

Objective: : Most affective neuroscience studies use pictures from the International Affective Picture System or standard facial expressions to elicit emotional experiences. The attention system, including the prefrontal cortex, can mediate emotional regulation in response to stimulation with emotional faces. We hypothesized that emotional experience is associated with brain activity within the neocortex. In addition, modification within the neocortex may be associated with brain activity within the attention system. Methods: : Thirty-one healthy adult participants were recruited to be assessed for emotional expression using clinical scales of happiness, sadness, anxiety, and anger as and for emotional experience using brain activity in response to pictures of facial emotional expressions. The attention system was assessed using brain activity in response to the go-no-go task. Results: : We found that emotional experience was associated with brain activity within the frontotemporal cortices, while emotional expression was associated with brain activity within the temporal and insular cortices. In addition, the association of brain activity between emotional experiences and expressions of sadness and anxiety was affected by brain activity within the anterior cingulate gyrus in response to the go-no-go task. Conclusion: : Emotional expression may be associated with brain activity within the temporal cortex, whereas emotional experience may be associated with brain activity within the frontotemporal cortices. In addition, the attention system may interfere with the connection between emotional expression and experience.

Kaempferol stimulation of autophagy regulates the ferroptosis under the oxidative stress as mediated with AMP-activated protein kinase.

Recent studies have highlighted the positive effects of Kaempferol (KP), including its anti-inflammatory and antioxidant properties. However, its impact on oxidative damage induced by heavy metals and pro-inflammatory mediators, such as arachidonic acid (AA), has not yet been identified. Our objective was to specifically evaluate liver damage due to AA + iron-induced oxidative stress, both in vitro and in vivo. In HepG2 cells, KP activated the AMP-activated protein kinase (AMPK), suggesting a hepatoprotective effect through AMPK inhibition, as assessed by immunoblot and FACS analysis (EC50 = 10 µM). KP also stimulated autophagy, a degradation process that eliminates aged, damaged, and unnecessary components, via mTOR inhibition and ULK1 phosphorylation. This activation was further validated by the upregulation of autophagy-related genes (ATG5) and Beclin-1, along with the conversion of LC3BI to LC3BII. Ferroptosis, a non-apoptotic type of cell death characterized by oxidative stress from the production of reactive oxygen species (ROS) and excessive iron accumulation, was linked to the activation of autophagy, as confirmed through the protein expression of deferoxamine (DFO) and ferrostatin-1 (Fer-1), the representative ferroptosis inhibitors (positive controls). In mice, oral administration of KP demonstrated protective effects against CCl4-induced hepatotoxicity. In conclusion, KP provides hepatoprotective effects against oxidative stress induced by AA + iron treatment in vitro and CCl4 treatment in vivo.

Mediating effects of attention problems on the link between parenting style and internet gaming disorder in adolescents.

Background: Positive and negative parenting styles as well as psychiatric comorbidities including attention deficit hyperactivity disorder (ADHD) have been associated with internet gaming disorder (IGD) in children and adolescents. We hypothesized that ADHD and parenting style would be associated with IGD in adolescents. In addition, psychological status could mediate the link between parenting style and the severity of IGD. Methods: A total of 256 adolescents with IGD and 211 healthy internet game players and their mothers participated in the current study. Demographic data, gaming patterns, and psychological status including ADHD were recorded for all adolescents. The parenting style of each adolescent's mother was assessed using the Maternal Behavior Research Instrument (Korean version). Results: There were significant differences in the internet game play patterns, psychological status, and parenting styles between the IGD group and healthy internet game players. In the hierarchical logistic regression analysis, higher ADHD scores, less affective parenting styles, and less autonomous parenting styles, were significant predictors of IGD. In the mediation test, the ADHD score was found to mediate the association between affective and autonomous parenting styles and the severity of IGD. Conclusion: Attention problems could directly and indirectly mediate the relationship between positive parenting styles and the severity of IGD. Our findings have the potential to aid in the development of treatment plans for IGD and ADHD as well as to contribute to the development of educational resources regarding parenting styles.

Unraveling the Antioxidant Capacity of Spatholobi caulis in Nonalcoholic Fatty Liver Disease: A Multiscale Network Approach Integrated with Experimental Validation.

Nonalcoholic fatty liver disease (NAFLD) is a global health problem that is closely associated with obesity and metabolic syndrome. Spatholobi caulis (SC) is a herbal medicine with potential hepatoprotective effects; however, its active compounds and underlying mechanisms have not been fully explored. In this study, we combined a multiscale network-level approach with experimental validation to investigate SC's antioxidant properties and their impact on NAFLD. Data collection and network construction were performed, and active compounds and key mechanisms were identified through multi-scale network analysis. Validation was conducted using in vitro steatotic hepatocyte models and in vivo high-fat diet-induced NAFLD models. Our findings revealed that SC treatment improved NAFLD by modulating multiple proteins and signaling pathways, including AMPK signaling pathways. Subsequent experiments showed that SC treatment reduced lipid accumulation and oxidative stress. We also validated SC's effects on AMPK and its crosstalk pathways, emphasizing their role in hepatoprotection. We predicted procyanidin B2 to be an active compound of SC and validated it using a lipogenesis in vitro model. Histological and biochemical analyses confirmed that SC ameliorated liver steatosis and inflammation in mice. This study presents SC's potential use in NAFLD treatment and introduces a novel approach for identifying and validating active compounds in herbal medicine.

Correlation Between Attention Deficit Hyperactivity Disorder, Internet Gaming Disorder or Gaming Disorder.

OBJECTIVE: Individuals with internet gaming disorder (IGD) or gaming disorder (GD) had a higher prevalence of ADHD than individuals without IGD or GD. The overpathologizing of excessive gaming behaviors may be associated with the functional impairment due to ADHD in individuals with GD. METHODS: The present study was designed to compare the gaming patterns, accompanying psychopathology, and co-occurring psychiatric disorders, especially ADHD, between clinical and general gamer samples (17-29 years old). RESULTS: Out of the nine IGD criteria, the item "functional impairment" had low diagnostic accuracy in participants with IGD or GD. The IGD (GD) group had a higher prevalence of ADHD compared to the general gamer group. Conversely, there was a higher prevalence of IGD (GD) in the ADHD group compared to the non-ADHD group. DISCUSSION: The possibility of ADHD should be considered when IGD or GD is diagnosed in patients with problematic Internet gaming.

Subcortical volume analysis in non-suicidal self-injury adolescents: A pilot study.

Given the high prevalence of non-suicidal self-injury (NSSI) among teenagers worldwide, the underlying mechanisms promoting such behavior must be urgently investigated. This study aimed to investigate neurobiological changes in the regional brain in adolescents with NSSI by comparing the volumes of the subcortical structures of 23 female adolescents with NSSI and 23 healthy controls with no history of psychiatric diagnosis or treatment. The NSSI group comprised those who underwent inpatient treatment for non-suicidal self-harm behavior at the Department of Psychiatry at Daegu Catholic University Hospital from July 1, 2018, to December 31, 2018. The control group comprised healthy adolescents from the community. We compared differences in the volume of the bilateral thalamus, caudate, putamen, hippocampus, and amygdala. All statistical analyses were conducted using SPSS Statistics Version 25. The NSSI group exhibited decreased subcortical volume in the left amygdala and marginally decreased subcortical volume in the left thalamus. Our results provide important clues about adolescent NSSI's underlying biology. Analysis of subcortical volumes between the NSSI and normal groups revealed subcortical volume differences in the left amygdala and thalamus, part of the core cerebral regions responsible for emotional processing and regulation, which may help explain the neurobiological mechanism of NSSI.

Integrative approach to uncover antioxidant properties of Bupleuri Radix and its active compounds: Multiscale interactome-level analysis with experimental validation.

Acute and chronic liver disease are global problems with high morbidity and mortality. Bupleuri Radix (BR) is an herbal medicine that has been prescribed empirically in traditional Asian medicine to modulate liver metabolism. However, its active compounds and therapeutic mechanisms remain unclear. Here, we integrated a network-based approach and experimental validation to elucidate BR's therapeutic potential in treating oxidative liver injury. Our approach incorporated data collection and network construction utilizing bioinformatics tools, and identified active compounds and key mechanisms based on the multiscale interactome. The proposed mechanisms were validated using an in vitro oxidative stress model and an in vivo carbon tetrachloride-induced model. We found that BR ameliorated the oxidative hepatic damage by acting on multiple proteins (STAT3, TNF, and BCL2) and signaling pathways (AMPK and Hippo signaling pathways). Subsequent in vitro experiments confirmed that BR significantly inhibited oxidative stress and mitochondrial damage. We further validated the effect of BR on the AMPK and Hippo-YAP pathways; a key mechanism for the antioxidant properties of BR. We prioritized the active compounds in BR based on a multiscale interactome-based approach, and further experiments revealed that saikosaponin A was a key active compound involved in hepatocyte protection (EC50 = 50 µM), similar to the result using metformin and 5-aminoimidazole-4-carboxamide ribonucleotide. Histochemistry and blood biochemistry established that BR significantly inhibited carbon tetrachloride-induced oxidative tissue damage in mice. Thus, BR can be used to develop novel therapeutics for oxidative liver injury. Moreover, we suggest a novel strategy to prioritize and validate the active compounds and key mechanisms of herbal medicine based on the multiscale interactome.

Comparative bioaccumulation, translocation, and phytotoxicity of metal oxide nanoparticles and metal ions in soil-crop system.

Exposure of the soil environment to metal nanoparticles (MNPs) has been extensive because of their indiscriminate use and the disposal of MNP products in various applications. In MNP-amended soil, various crops can absorb the nanoparticles, and accumulation of the MNPs in farm products has potential risks for bioconcentration in humans and livestock. Here, we evaluated the comparative bioaccumulation, translocation, and phytotoxicity of MNPs (ZnO and CuO NPs) and metal ions (Zn(NO3)2 and Cu(NO3)2) in four different crops, namely lettuce, radish, bok choy, and tomato. We carried out pot experiments to evaluate the phytotoxicity in the crops from the presence of MNPs and metal ions. Phytotoxicity from different treatments differed depending on the plant species, and metal types. In addition, exposure to Zn and Cu showed positive dose-dependent effects on their bioaccumulation in each crop. However, there were no significant differences in metal bioaccumulation depending on whether the crops were exposed to MNPs or metal ions. By calculating the bioconcentration factor (BCF) and translocation factor (TF), we were able to estimate the biological uptake and translocation abilities of MNPs and metal ions for each crop. It was found that lettuce and radish had greater BCFs than bok choy and tomato, while bok choy and tomato had higher TFs. Also, the uptake and translocation of Zn were better than those of Cu. However, the values for BCF and TF for each crop showed no significant differences between MNP and metal ion exposure. A micro X-ray fluorescence (µ-XRF) spectrometer analysis demonstrated that only Zn elements appeared in the primary veins and edges of all leaves and the storage root of radish. Our study aims to estimate bioaccumulation, translocation, and the implied potential risks from MNPs accumulated in different plant species.

Coordination of AMPK and YAP by Spatholobi Caulis and Procyanidin B2 Provides Antioxidant Effects In Vitro and In Vivo.

The liver is vulnerable to oxidative attacks from heavy metals, such as iron, as well as some drugs, including acetaminophen. It has been shown that enhanced oxidative stress in the liver leads to excessive ROS production and mitochondrial dysfunction, resulting in organ injury. The beneficial effects of Spatholobi Caulis (SC), a natural herbal medicine, include treating ischemic stroke, inhibiting tumor cell invasion, pro-angiogenic activities, and anti-inflammatory properties. Scientific studies on its effects against hepatotoxic reagents (e.g., iron and acetaminophen), as well as their underlying mechanisms, are insufficient. This study examined the antioxidant effects and mechanisms of SC in vitro and in vivo. In cells, the proinflammatory mediator, arachidonic acid (AA), plus iron, significantly induced an increase in ROS generation, the damage in mitochondrial membrane potential, and the resulting apoptosis, which were markedly blocked by SC. More importantly, SC affected the activation of AMP-activated protein kinase (AMPK)-related proteins, which were vital to regulating oxidative stress in cells. In addition, SC mediated the expression of Yes-associated protein (YAP)-related proteins. Among the active compounds in SC, the procyanidin B2, but not liquiritigenin, daidzein, and genistein, significantly inhibited the cytotoxicity induced by AA + iron, and activated the LKB1-AMPK pathway. In mice, the oral administration of SC alleviated the elevations of ALT and histological changes by the acetaminophen-induced liver injury. These results reveal the potential of SC and a key bioactive component, procyanidin B2, as antioxidant candidates for hepatoprotection.

Correlations Between Psychological Status and Perception of Facial Expression.

OBJECTIVE: Facial affect recognition is associated with neuropsychological status and psychiatric diseases. We hypothesized that facial affect recognition is associated with psychological status and perception of other affects. METHODS: A total of 80 images depicting facial affect, including 20 Neutral, 20 Angry, 20 Fear, and 20 Sad, were screened for use in our research. A total of 100 healthy individuals were asked to rate these images using a 10-point Likert scale and complete psychological scales assessing the emotional statuses and cognitive functions. RESULTS: The participants' emotional state of aggression, attention, and impulsivity may have been associated with their interpretation of the Angry facial expressions. The participants often rated the Angry facial expressions as Fear. The participants rated Fear images as Angry or Sad. In response to a Sad facial expression, the participants reported psychological statuses of attention and impulsivity which were associated with the facial expression rating. The participants rated the Sad expression as Angry or Fear. CONCLUSION: The psychological statuses of the participants were significantly correlated with their interpretation of facial affects. In particular, a psychological state of attention was often correlated with incorrect affect ratings. Attention and impulsivity could affect the rating of the sad facial expressions.

Angelica gigas NAKAI and Its Active Compound, Decursin, Inhibit Cellular Injury as an Antioxidant by the Regulation of AMP-Activated Protein Kinase and YAP Signaling.

Natural products and medicinal herbs have been used to treat various human diseases by regulating cellular functions and metabolic pathways. Angelica gigas NAKAI (AG) helps regulate pathological processes in some medical fields, including gastroenterology, gynecology, and neuropsychiatry. Although some papers have reported its diverse indications, the effects of AG against arachidonic acid (AA)+ iron and carbon tetrachloride (CCl4) have not been reported. In HepG2 cells, AA+ iron induced cellular apoptosis and mitochondrial damage, as assessed by mitochondrial membrane permeability (MMP) and the expression of apoptosis-related proteins. On the other hand, AG markedly inhibited these detrimental phenomena and reactive oxygen species (ROS) production induced by AA+ iron. AG activated the liver kinase B1 (LKB1)-dependent AMP-activated protein kinase (AMPK), which affected oxidative stress in the cells. Moreover, AG also regulated the expression of yes-associated protein (YAP) signaling as mediated by the AMPK pathways. In mice, an oral treatment of AG protected against liver toxicity induced by CCl4, as indicated by the plasma and histochemical parameters. Among the compounds in AG, decursin had antioxidant activity and affected the AMPK pathway. In conclusion, AG has antioxidant effects in vivo and in vitro, indicating that natural products such as AG could be potential candidate for the nutraceuticals to treat various disorders by regulating mitochondrial dysfunction and cellular metabolic pathways.

A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine.

Liver cancer has relatively few early symptoms and is usually diagnosed in the advanced stage. Sorafenib is the only first-line anticancer drug approved by the Food and Drug Administration (FDA) for advanced HCC; however, its use is limited due to resistance. Therefore, the development of new drugs is essential to achieving customized treatment. Many studies have suggested that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) is associated with metastasis and cancer formation and progression in various cancers. In the present study, YAP was overexpressed in various patient-derived hepatocarcinoma (HCC) tissues. In addition, this study examined whether evodiamine (which has anticancer effects) can inhibit YAP and, if so, modulate HCC. Evodiamine significantly reduced both the YAP level and cell growth of HCC in a dose-dependent manner. Biochemical analysis indicated mitochondria dysfunction-mediated apoptosis to be the cause of the reduction in HCC cell growth by evodiamine. YAP was overexpressed in metastatic HCC tissues as well when compared to primary HCC tissues. Migration and invasion analysis showed that evodiamine has anti-metastatic ability on Hep3B and Huh-7 cells and reduces the level of vimentin, an EMT marker. In conclusion, YAP is a critical target in HCC therapy, and evodiamine can be an effective HCC anticancer drug by reducing the YAP level.

Association Between Adolescent Internet Gaming and Adult Problematic Web-Based Board Gaming.

Introduction: The results of studies comparing the characteristics of Internet gaming with those of Internet gambling have been controversial. We hypothesized that problematic web-based board gaming behaviors are associated with psychological and social interaction factors. We also hypothesized that non-problematic adolescent Internet gaming is a protective factor against problematic web-based board gaming and that problematic Internet gaming is a predictive factor for problematic web-based board gaming. Methods: We recruited 104 adults who reported engaging in web-based gaming. All participants were asked to complete the Problematic Web Board Gameplay Scale, Center for Epidemiologic Studies Depression Scale (CESD), State-Trait Anxiety Inventory (STAI), Adult Attention Deficit/Hyperactivity Disorder Self-Report Scale (K-AADHD), Family Environmental Scale (FES), Social Avoidance and Distress Scale (SADS), and questionnaires on their web-based board gaming patterns and Internet gaming history. Results: Problematic web-based board gamers showed a lower history of adolescent Internet gaming but a greater rate of problematic Internet gaming compared with healthy web-based board gamers. Moreover, problematic web-based board gamers showed an increase in CES-D, STAI, K-AADHD, and SADS scores but decreased FES scores compared with healthy web-based board gamers. Joblessness; less experience as an Internet gamer; a history of problematic Internet gaming; higher CES-D, STAI, and K-AADHD scores; and lower FES scores were significant predictors of problematic web-based board gaming. Discussion: Psychological, social, and environmental factors can positively influence problematic Web-based board gaming. Healthy Internet gaming during adolescence may play a preventive role in adult problematic web-based board gaming. However, because adolescent problematic Internet gaming tends to lead to problematic web-based board gaming, measures should be taken to prevent it.

A mixed herbal extract as an adjunctive therapy for attention deficit hyperactivity disorder: A randomized placebo-controlled trial.

BACKGROUND: Methylphenidate improves clinical symptoms and brain activity in attention deficit hyperactivity disorder (ADHD) patients through the attention-regulation network's dopamine system. Additionally, water-soluble extracts (HX106) of four plants (Gastrodia elata Blume, Liriope platyphylla Wang et Tang, Salvia miltiorrhiza Bunge, and Dimocarpus longan Lour) improve cognitive function. We hypothesized that the combination of HX106 and methylphenidate would improve ADHD symptoms and brain activity of the attention network more effectively than the combination of placebo and methylphenidate. METHODS: Twenty-seven patients with ADHD were administered a herbal mixture and methylphenidate (n=13), or placebo and methylphenidate (n=14) during a 4-week, randomized, double-blind, placebo-controlled clinical trial. Changes in ADHD symptoms (K-ARS scores), as well as brain activity and functional connectivity, were assessed at baseline and 4 weeks later. RESULTS: The HX106 group showed a greater improvement in total attention (16.8%) and inattention (17.2%) scores than the placebo group. The HX106 group showed increased brain activity within the left precuneus compared to the placebo group. The HX106 group also showed increased functional connectivity from the precuneus seed to the left middle temporal gyrus compared with the placebo group. In all participants, the changes in K-ARS scores were negatively correlated with changes in brain activity in the left middle temporal gyrus. CONCLUSIONS: HX106 enhanced the effect of methylphenidate on ADHD symptoms and increased brain activity in the attention-regulation network. Therefore, HX106 may be an effective adjunctive therapy for patients with ADHD.

Impact of attention-deficit/hyperactivity disorder comorbidity on longitudinal course in Internet gaming disorder: a 3-year clinical cohort study.

BACKGROUND: Although attention-deficit/hyperactivity disorder (ADHD) symptoms were identified as a key risk factor for Internet gaming disorder (IGD), the effect of ADHD comorbidity on longitudinal course of IGD in the clinical population remains to be further examined. This study aimed to investigate whether ADHD comorbidity in IGD patients affects the recovery, recurrence rates, and trajectories of IGD symptoms, and examine the relationship between the changes in IGD and ADHD symptoms. METHODS: The study included 128 IGD patients without any psychiatric comorbidities (pure-IGD group) and 127 IGD patients with comorbid ADHD (ADHD-IGD group) aged 11 to 42 years. IGD and ADHD were diagnosed according to DSM-5 criteria at enrollment. Participants were offered 8-week treatment with additional care provided as needed and followed up over a 3-year period. IGD diagnosis was reassessed annually and used as a dichotomous outcome. The severity of IGD and ADHD symptoms was measured using the Young Internet Addiction Scale and the Korean ADHD rating scale, respectively, at baseline and each annual follow-up. RESULTS: The recovery rates of IGD by Year 3 were 60% and 93% in ADHD-IGD and in pure-IGD groups, respectively. The ADHD-IGD group showed lower rates of recovery, higher odds of recurrence within 1 year, and higher severity of IGD symptoms over time than the pure-IGD group. Family environment was also associated with the trajectories of IGD symptoms. The changes in ADHD symptoms were significantly associated with the changes in IGD symptoms. CONCLUSIONS: This study found that ADHD comorbidity in IGD patients was associated with poor clinical course of IGD and that the changes in ADHD symptoms were associated with the changes in IGD symptoms over time. Our findings suggest that evaluation and treatment of ADHD symptoms and family environment in IGD patients may be important in improving the prognosis of IGD.