Exosome-mediated delivery of super-repressor IκBα alleviates inflammation and joint damages in rheumatoid arthritis.

BACKGROUND: This study aims to investigate the potential anti-inflammatory effects of exosomes engineered to carry super-repressor IκB (Exo-srIκB), an exosome-based NF-κB inhibitor, in the context of RA. METHODS: Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were collected from patients diagnosed with RA and treated with Exo-srIκB to test the therapeutic potential. Flow cytometry analysis was performed to assess the production of inflammatory cytokines (IL-17A and GM-CSF) by the cells. ELISA was utilized to measure the levels of TNF-α, IL-17A, IL-6, and GM-CSF. Arthritis was induced in SKG mice by intraperitoneal injection of curdlan. DBA/1 J mice were used in collagen-induced arthritis (CIA) experiments. After the development of arthritis, mice were injected with either Exo-Naïve (control exosome) or Exo-srIκB. Arthritis scores were recorded biweekly, and histological observations of the ankle joint were conducted using H&E and safranin-O staining. Additionally, bone erosion was evaluated using micro-CT imaging. RESULTS: In the ex vivo study involving human PBMCs and SFMCs, treatment with Exo-srIκB demonstrated a notable reduction in inflammatory cytokines. Furthermore, in both the SKG and CIA models, Exo-srIκB treatment exhibited significant reductions in inflammation, cartilage destruction, and bone erosion within the joint tissues when compared to the Exo-Naive control group. Additionally, the radiographic score assessed through microCT showed a significant decrease compared to the Exo-Naive control group. CONCLUSION: Overall, these findings suggest that Exo-srIκB possesses anti-inflammatory properties in human RA cells and animal models, making it a promising therapeutic candidate for the treatment of RA.

Artificial Intelligence Model Assisting Thyroid Nodule Diagnosis and Management: A Multicenter Diagnostic Study.

CONTEXT: It is not clear how to integrate artificial intelligence (AI)-based models into diagnostic workflows. OBJECTIVE: To develop and validate a deep-learning-based AI model (AI-Thyroid) for thyroid cancer diagnosis, and to explore how this improves diagnostic performance. METHODS: The system was trained using 19 711 images of 6163 patients in a tertiary hospital (Ajou University Medical Center; AUMC). It was validated using 11 185 images of 4820 patients in 24 hospitals (test set 1) and 4490 images of 2367 patients in AUMC (test set 2). The clinical implications were determined by comparing the findings of six physicians with different levels of experience (group 1: 4 trainees, and group 2: 2 faculty radiologists) before and after AI-Thyroid assistance. RESULTS: The area under the receiver operating characteristic (AUROC) curve of AI-Thyroid was 0.939. The AUROC, sensitivity, and specificity were 0.922, 87.0%, and 81.5% for test set 1 and 0.938, 89.9%, and 81.6% for test set 2. The AUROCs of AI-Thyroid did not differ significantly according to the prevalence of malignancies (>15.0% vs ≤15.0%, P = .226). In the simulated scenario, AI-Thyroid assistance changed the AUROC, sensitivity, and specificity from 0.854 to 0.945, from 84.2% to 92.7%, and from 72.9% to 86.6% (all P < .001) in group 1, and from 0.914 to 0.939 (P = .022), from 78.6% to 85.5% (P = .053) and from 91.9% to 92.5% (P = .683) in group 2. The interobserver agreement improved from moderate to substantial in both groups. CONCLUSION: AI-Thyroid can improve diagnostic performance and interobserver agreement in thyroid cancer diagnosis, especially in less-experienced physicians.

Clinical effects of bacteremia in sepsis patients with community-acquired pneumonia.

BACKGROUND: Data regarding the clinical effects of bacteremia on severe community-acquired pneumonia (CAP) are limited. Thus, we investigated clinical characteristics and outcomes of severe CAP patients with bacteremia compared with those of subjects without bacteremia. In addition, we evaluated clinical factors associated with bacteremia at the time of sepsis awareness. METHODS: We enrolled sepsis patients diagnosed with CAP at emergency departments (EDs) from an ongoing nationwide multicenter observational registry, the Korean Sepsis Alliance, between September 2019 and December 2020. For evaluation of clinical factors associated with bacteremia, we divided eligible patients into bacteremia and non-bacteremia groups, and logistic regression analysis was performed using the clinical characteristics at the time of sepsis awareness. RESULT: During the study period, 1,510 (47.9%) sepsis patients were caused by CAP, and bacteremia was identified in 212 (14.0%) patients. Septic shock occurred more frequently in the bacteremia group than in the non-bacteremia group (27.4% vs. 14.8%; p < 0.001). In multivariable analysis, hematologic malignancies and septic shock were associated with an increased risk of bacteremia. However, chronic lung disease was associated with a decreased risk of bacteremia. Hospital mortality was significantly higher in the bacteremia group than in the non-bacteremia group (27.3% vs. 40.6%, p < 0.001). The most prevalent pathogen in blood culture was Klebsiella pneumoniae followed by Escherichia coli in gram-negative pathogens. CONCLUSION: The incidence of bacteremia in severe CAP was low at 14.0%, but the occurrence of bacteremia was associated with increased hospital mortality. In severe CAP, hematologic malignancies and septic shock were associated with an increased risk of bacteremia.

Differential patterns of lifestyle behaviors among low- and high-income postmenopausal women in Korea: a latent class analysis.

BACKGROUND: Healthy lifestyle behaviors among postmenopausal women are important to prevent chronic diseases and improve health later in life. Heterogeneous lifestyle patterns may exist among postmenopausal women, and socioeconomic status (SES) is a critical determinant of lifestyle behaviors. However, little is known about distinct SES-specific patterns of lifestyle behaviors among postmenopausal women. Thus, this study used latent class analysis to identify subgroups of postmenopausal women with different health behaviors according to income and to examine the predictors of income-specific subgroups. METHODS: We analyzed nationally representative data from the Eighth Korea National Health and Nutrition Examination Survey, collected in 2019 and 2020. We used nine lifestyles (i.e., current smoking and drinking, high-risk drinking, walking, muscle-strengthening exercise, sleep, vegetable and fruit intakes, and weight control efforts). We conducted a multiple-group latent class analysis using monthly household income as a proxy for SES. The monthly household income variable was calculated by standardizing monthly household income by the number of family members and then divided into quintiles. We classified the participants into low- (i.e., Q1 and Q2) and high-income (i.e., Q3, Q4, and Q5) groups. RESULTS: Although the three-class models best fit the data of low- and high-income groups, we found differential patterns by income: (a) for low-income group, "relatively healthy (RH)," "lowest physical activity, insufficient fruit intake, and no intention to control weight," and "high-risk drinking and insufficient fruit intake" classes and (b) for high-income group, "RH," "lowest physical activity," "high-risk drinking and insufficient fruit intake and sleep" classes. The proportion of the RH class was largest in both groups. However, lifestyle patterns in low-income group showed multiple and unhealthy characteristics than those in high-income group. CONCLUSIONS: This study suggests that different underlying lifestyle patterns exist in postmenopausal women with low- and high-income. To promote healthy behaviors among postmenopausal women, health professionals should develop and apply lifestyle interventions tailored to lifestyle pattern characteristics according to income.

Design of an effective small expression tag to enhance GPCR production in E. coli-based cell-free and whole cell expression systems.

G protein-coupled receptors (GPCRs) play crucial roles in sensory, immune, and tumor metastasis processes, making them valuable targets for pharmacological and sensing applications in various industries. However, most GPCRs have low production yields in Escherichia coli (E. coli) expression systems. To overcome this limitation, we introduced AT10 tag, an effective fusion tag that could significantly enhance expression levels of various GPCRs in E. coli and its derived cell-free protein synthesis (CFPS) system. This AT10 tag consisted of an A/T-rich gene sequence designed via optimization of translation initiation rate. It is translated into a short peptide sequence of 10 amino acids at the N-terminus of GPCRs. Additionally, effector proteins could be utilized to suppress cytotoxicity caused by membrane protein expression, further boosting GPCR production in E. coli. Enhanced expression of various GPCRs using this AT10 tag is a promising approach for large-scale production of functional GPCRs in E. coli-based CFPS and whole cell systems, enabling their potential utilization across a wide range of industrial applications.

Associations Between Gender-Specific Substance Use Patterns and Mental Health Among Adolescents in the Republic of Korea: A Latent Class Analysis.

PURPOSE: Although gender differences in adolescent substance use are complex and substance use accompanies mental health problems, most previous studies have focused on gender-specific association between single substance use and mental health. This study aimed to investigate gender-specific substance use patterns and to examine their association with mental health characteristics. METHODS: Nationally representative data from the Korea Youth Risk Behavior Survey collected in 2018 were analyzed. To identify substance use patterns among male adolescents (n = 30,463) and female adolescents (n = 29,577), multiple-group latent class analysis was conducted using eight substance use indicators. In addition, we conducted a latent class analysis with covariates to examine the association between substance use patterns and mental health characteristics. RESULTS: Among both gender samples, the four-class model best fit the data: nonusers (86.4%), frequent smokers (2.9%), risky drinkers (7.1%), and heavy tobacco and alcohol users with lifetime heated tobacco product use (3.6%) for male adolescents, and nonusers (89.8%), frequent smokers (0.5%), risky drinkers (8.0%), and heavy tobacco and alcohol users with a drunkenness episode (1.7%) for female adolescents. Depression, suicidal plans, and suicidal attempts predicted the latent class model for both genders. In addition, stress level predicted the latent class model for female adolescents. CONCLUSIONS: The findings indicate that homogeneous patterns of substance use by gender are differentially associated with mental health problems. Therefore, health professionals should develop interventions tailored to gender-specific substance use patterns, taking into account the mental health characteristics of each pattern.

Body Composition and Bone Mineral Density in Postmenopausal Women with Advanced Knee Osteoarthritis Undergoing Surgical Treatment.

OBJECTIVES: This study aimed to demonstrate the bone mineral density (BMD) and body composition in postmenopausal women with knee osteoarthritis (OA) who underwent surgical treatment, such as total knee arthroplasty, osteotomy, or meniscectomy. METHODS: A total of 254 women with OA aged 50 years who underwent surgical treatment were enrolled in this study. We evaluated obesity-related factors, muscle components, and BMD using dual-energy X-ray absorptiometry. RESULTS: No significant differences were noted in the BMD of the hip joint between the symptomatic side of the leg with knee OA and the contralateral side. However, when comparing the BMD of each component, the results indicated a significantly higher BMD in the obesity group based on body mass index (BMI). When defining sarcopenic obesity (SO) using various indicators of obesity (BMI, the estimated visceral adipose tissue area, android/gynoid ratio, and total body fat percentage), the prevalence of SO in the OA group who underwent surgical treatment ranged from 22.0% to 49.6%. CONCLUSIONS: This study investigated obesity-related factors in patients with advanced knee OA who underwent surgery, revealing a high prevalence of overweight/obese individuals, the presence of SO, and a complex relationship between obesity, body composition, and bone density, highlighting the potential protective effects of weight-bearing on bone health while exploring the impact of sarcopenia on bone density differences in the context of OA. Depending on various definitions of obesity, diverse proportions of SO in patients with OA have been observed, and further detailed research is required to understand its impact on the condition.

Associations between the Frequency and Quantity of Heated Tobacco Product Use and Smoking Characteristics among Korean Smoking Adolescents.

PURPOSE: Although heated tobacco product (HTP) use among adolescents is an emerging public health problem, little is known about the frequency and quantity of HTP use. Thus, we investigated the associations between the frequency and quantity of HTP use and smoking characteristics (i.e., combustible cigarette [CC] and electronic cigarette [EC] use, and attempts to quit smoking) among CC-smoking adolescents. METHODS: We analyzed nationally representative data from 2,470 Korean adolescents who were current CC smokers. To investigate our aim, we conducted multinomial logistic and logistic regression analyses. RESULTS: We found that daily and heavier CC users had greater likelihoods of more frequent and heavier HTP use. In addition, dual users of CCs and ECs were more likely to use HTPs more frequently and heavily than CC users who did not use ECs. Moreover, daily EC users had the highest risk of frequent and heavy HTP use. The frequency and quantity of HTP use were not associated with attempts to quit smoking. Compared to CC-only use, dual use of CCs and HTPs was not associated with quitting attempts, and triple use of CCs, ECs, and HTPs was associated with a lower likelihood of quitting attempts. CONCLUSION: HTP use was less likely to displace CC use and promote attempts to quit smoking. Thus, strict regulations are required to prevent the promotion of HTPs as a substitute for CCs or as a means of quitting smoking. Additionally, health professionals should consider preventive interventions for HTP, as well as CC and EC use among adolescents.

miRNA-Induced Downregulation of IPMK in Macrophages Mediates Lipopolysaccharide-Triggered TLR4 Signaling.

Inositol polyphosphate multikinase (IPMK) is a pleiotropic enzyme responsible for the production of inositol polyphosphates and phosphoinositide. IPMK in macrophages was identified as a key factor for the full activation of the Toll-like receptor 4 (TLR4) signaling pathway and inflammation by directly interacting with tumor necrosis factor receptor-associated factor 6 (TRAF6). Here, dynamic changes of IPMK levels in lipopolysaccharide (LPS)-stimulated macrophages and their functional significance were investigated. Both the mRNA and protein levels of IPMK were acutely decreased in mouse and human macrophages when cells were stimulated with LPS for between 1 and 6 h. Analysis of the 3' untranslated region (UTR) of mouse IPMK mRNA revealed a highly conserved binding site for miR-181c. Transfection of miR-181c mimics into RAW 264.7 macrophages led to decreased IPMK 3'UTR-luciferase reporter activity and lowered endogenous IPMK levels. When the genomic deletion of a 33-bp fragment containing a putative miR-181c-binding site was introduced within the IPMK 3'UTR of RAW 264.7 macrophages (264.7Δ3'UTR), LPS-triggered downregulation of IPMK levels was prevented. LPS treatment in 264.7Δ3'UTR macrophages decreased TLR4-induced signaling and the expression of proinflammatory cytokines. In response to LPS stimulation, K63-linked ubiquitination of TRAF6 was impaired in 264.7Δ3'UTR macrophages, suggesting an action of IPMK in the suppression of TRAF6 activation. Therefore, our findings reveal that LPS-mediated suppression of IPMK regulates the full activation of TLR4 signaling and inflammation in macrophages.

Analysis of Single-Cell Transcriptome and Surface Protein Expression in Ankylosing Spondylitis Identifies OX40-Positive and Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Positive Pathogenic Th17 Cells.

OBJECTIVE: To demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single-cell transcriptome and surface protein expression, and to unveil the molecular characteristics of pathogenic Th17 cells. METHODS: This study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor. Single-cell transcriptomes of 6 patients with active AS were studied along with cellular indexing of transcriptomes and epitopes by sequencing. We also assessed the outcome of targeting OX40 and glucocorticoid-induced tumor necrosis factor receptor (GITR) on the surface of Th17 cells in a mouse model of curdlan-injected SKG mice in which anti-GITR ligand and/or anti-OX40 ligand were used. RESULTS: We identified pathogenic Th17 cells as polyfunctional interleukin-17A (IL-17A)- and interferon-γ (IFNγ)-producing memory CD4+ T cells, with clinically supportive evidence for their pathogenic roles at sites of inflammation in AS. Transcriptome and flow cytometric analyses revealed that the coexpression of TNFRSF4 (OX40) and TNFRSF18 (GITR) is increased in pathogenic Th17 cells. Suppression of ligand receptor interactions in vivo through OX40 and GITR effectively suppressed clinical arthritis and decreased pathogenic Th17 cells in the curdlan-injected SKG mouse model. CONCLUSION: Our results have implications for the understanding of pathogenic Th17 cells in AS patients and suggest potential therapeutic targets.

Role of alcohol media literacy in alcohol use among children and adolescents: a systematic review.

Enhancing alcohol media literacy (AML) is a critical strategy to attenuate negative effects of alcohol-related media messages. We aimed to systematically review previous studies on AML in children and adolescents. Through database and hand searches, we identified four non-experimental and 13 experimental studies. From the 17 studies, we extracted data on theoretical framework, AML measures, intervention contents and main findings. Our review revealed the following. First, nine and four studies used a single theory and at least two theories, respectively. The most frequently used theory was the Message Interpretation Process model. Second, 13 studies assessed AML using participant self-reporting or evaluators' ratings of participant performance, but no study reported validities of AML measures. Eight studies assessed tobacco or general media literacy as well as AML. Third, all experimental studies used three to five media literacy core concepts proposed by the Center for Media Literacy in AML interventions. Finally, all non-experimental studies found strong cross-sectional associations between higher AML and improved drinking outcomes; all experimental studies found strong intervention effects, such as an increase in AML or improvement in drinking outcomes. In addition, intervention effects differed across participants' gender and drinking experiences. Given our review, health professionals should implement strategies to enhance children and adolescents' AML. Future research should investigate (i) causal inferences in non-experimental studies, (ii) long-term intervention effects in experimental studies and (iii) differences in intervention effects across participants' characteristics, while using solid theoretical frameworks and multidimensional AML concepts.

Currently, alcohol consumption and great exposure to alcohol-related media messages in youth are significant public health concerns. After systematically reviewing non-experimental studies on alcohol media literacy (AML) in children and adolescents, we found that high AML levels were associated with improved drinking-related characteristics: a decrease in positive alcohol expectancies, intention to drink and risk of alcohol consumption. Additionally, we found that AML education targeting children and adolescents was effective in enhancing AML and improving the aforementioned drinking-related characteristics. Given our findings, we strongly recommend providing AML education to children and adolescents in order to attenuate negative effects of alcohol-related media messages on drinking-related characteristics.

Enhancement of anti-tumor activity in melanoma using arginine deiminase fused with 30Kc19α protein.

Arginine deiminase (ADI) is a microbial-derived enzyme which catalyzes the conversion of L-arginine into L-citrulline. ADI originating from Mycoplasma has been reported to present anti-tumor activity against arginine-auxotrophic tumors, including melanoma. Melanoma cells are sensitive to arginine depletion due to reduced expression of argininosuccinate synthase 1 (ASS1), a key enzyme for arginine biosynthesis. However, clinical applications of recombinant ADI for melanoma treatment present some limitations. Since recombinant ADI is not human-derived, it shows instability, proteolytic degradation, and antigenicity in human serum. In addition, there is a problem of drug resistance issue due to the intracellular expression of once-silenced ASS1. Moreover, recombinant ADI proteins are mainly expressed as inclusion body forms in Escherichia coli and require a time-consuming refolding process to turn them back into active form. Herein, we propose fusion of recombinant ADI from Mycoplasma hominis and 30Kc19α, a cell-penetrating protein which also increases stability and soluble expression of cargo proteins, to overcome these problems. We inserted matrix metalloproteinase-2 cleavable linker between ADI and 30Kc19α to increase enzyme activity in melanoma cells. Compared to ADI, ADI-LK-30Kc19α showed enhanced solubility, stability, and cell penetration. The fusion protein demonstrated selective cytotoxicity and reduced drug resistance in melanoma cells, thus would be a promising strategy for the improved efficacy in melanoma treatment. KEY POINTS: • Fusion of ADI with 30Kc19α enhances soluble expression and productivity of recombinant ADI in E. coli • 30Kc19α protects ADI from the proteolytic degradation by shielding effect, helping ADI to remain active • Intracellular delivery of ADI by 30Kc19α overcomes ADI resistance in melanoma cells by degrading intracellularly expressed arginine.

Enhanced anti-cancer effect using MMP-responsive L-asparaginase fused with cell-penetrating 30Kc19 protein.

As the acute lymphoblastic leukaemia (ALL) develops, expression of L-asparaginase (ASNase) protein is known to decrease. Therefore, deficiency of the ASNase protein would be regarded as one of the significant indications of the ALL. For the treatment of ALL, recombinant ASNase protein derived from bacterial origin is used which causes cytotoxicity by deprivation of Asn. However, short half-life of the protein is an obstacle for medical use. In order to overcome this limit, recombinant ASNase was fused to 30Kc19 with protein-stabilizing and cell-penetrating properties. As the 30Kc19 protein may induce steric hindrance, we further added a PLGLAG linker sequence (LK) between the ASNase and 30Kc19. The treatment of ASNase-LK-30Kc19 fusion protein demonstrated enhanced stability, cell-penetrating property, and anti-cancer activity. Intracellular delivery of both the non-cleaved and cleaved forms of the protein were observed, suggesting that ASNase acted both internally and externally, performing high anti-cancer activity by effective depletion of intracellular Asn. Additionally, ASNase-LK-30Kc19 showed high selectivity towards cancer cells. In terms of the dosage, releasable ASNase from ASNase-LK-30Kc19 reached the same half-maximal inhibitory concentration at a concentration five times lower than non-releasable ASNase-30Kc19. Altogether, the findings suggest that this fusion approach has potential applications in the treatment of ALL.

IL-6 activates pathologic Th17 cell via STAT 3 phosphorylation in inflammatory joint of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, which is characterized by inflammation of the axial skeleton and the peripheral arthritis. An increase in the number of Th17 cells in patients with AS has been reported. Although Th17 cells have been involved in the induction of inflammation, recent data suggest that not all Th17 cells are pathogenic, showing regulatory function of Th17 cell. Cells producing both interferon-gamma (IFN-γ) and interleukin (IL)-17 have been reported to be the main pathologic Th17 (pTh17) cells that induce inflammation at sites of joint. Emerging evidence demonstrated that IL-6 has a main role in regulating the balance between inflammatory and regulatory T cells. However, there is no direct study to assess pTh17 cell with IL-6 in AS. Therefore, we evaluated the effect of IL-6 on pTh17 cell activation, and it's mechanism, using ex vivo and mouse model of AS. As a result, we found that pTh17 cell is dependent on the cytokine milieu with IL-6. We confirmed pTh17 cells play a pathogenic role at sites of inflammation. As a mechanism, it was revealed that IL-6 induced STAT 3 phosphorylation contributes to the increased pTh17 responses in AS patients with peripheral arthritis. Though validation of our results is required, IL-6 inhibitor can be a promising treatment for inflammation in AS patients with peripheral arthritis.

Deletion of IP6K1 in mice accelerates tumor growth by dysregulating the tumor-immune microenvironment.

A family of inositol hexakisphosphate kinases (IP6Ks) catalyzes the production of inositol pyrophosphate IP7 (5-diphosphoinositolpentakisphosphate) which is known to modulate various biological events such as cell growth. While targeting IP6K1 in various cancer cells has been well reported to control cancer cell motility and invasiveness, the role of host IP6K1 in tumor progression remains unknown. By using a syngeneic MC38 murine mouse colon carcinoma model, here we examined how host IP6K1 in the tumor microenvironment influences tumor growth. In IP6K1 knockout (KO) mice, the growth of MC38 tumor cells was markedly accelerated and host survival was significantly shortened compared with wild-type (WT). Our flow cytometric analysis revealed that tumors grown in IP6K1 KO mice had lower immune suppressive myeloid cells and M1 polarized macrophages. Notably, infiltration of both antigen-presenting dendritic cells and CD8+ cytotoxic T lymphocytes into the tumor tissues was remarkably abrogated in IP6K1 KO condition. These studies suggest that enhanced tumor growth in IP6K1 KO mice resulted from reduced anti-tumor immunity due to disturbed immune cell actions in the tumor microenvironment. In conclusion, we demonstrate that host IP6K1 acts as a tumor suppressor, most likely by fine-tuning diverse tumor-immune cell interactions, which might have implications for improving the host response against cancer progression.

Latent Class Analysis of Obesogenic Behaviors among Korean Adolescents: Associations with Weight-Related Outcomes.

This study aimed to explore sex-specific latent class models of adolescent obesogenic behaviors (OBs), predictors of latent class membership (LCM), and associations between LCM and weight-related outcomes (i.e., weight status and unhealthy weight control behaviors). We analyzed nationally representative data from the 2019 Korea Youth Risk Behavior Survey. To identify latent classes for boys (n = 29,841) and girls (n = 27,462), we conducted a multiple-group latent class analysis using eight OBs (e.g., breakfast skipping, physical activity, and tobacco product use). Moreover, we performed a multinomial logistic regression analysis and a three-step method to examine associations of LCM with predictors and weight-related outcomes. Among both sexes, the 3-class models best fit the data: (a) mostly healthy behavior class, (b) poor dietary habits and high Internet use class, and (c) poor dietary habits and substance use class. School year, residential area, academic performance, and psychological status predicted the LCM for both sexes. In addition, perceived economic status predicted the LCM for girls. The distribution of weight-related outcomes differed across sex-specific classes. Our findings highlight the importance of developing obesity prevention and treatment interventions tailored to each homogeneous pattern of adolescent OBs, considering differences in their associations with predictors and weight-related outcomes.

[Associations between Cigarette and Electronic Cigarette Use and Sleep Health in Korean Adolescents: An Analysis of the 14th (2018) Korea Youth Risk Behavior Surveys].

PURPOSE: This study aimed to understand the relationship between cigarette and electronic cigarette (e-cigarette) use and sleep health among Korean adolescents. METHODS: Using the 14th Korea Youth Risk Behavior Survey, we included 52,928 adolescents who responded to sleep satisfaction and sleep duration. Participants were classified into four groups: non-users, cigarette-only users, e-cigarette-only users, and dual users of both products. To examine the associations between cigarette and e-cigarette use and sleep health, data were analyzed using complex samples cross tabulation and complex samples logistic regression. RESULTS: Of the four groups, dual users reported the lowest level of sleep satisfaction and sleep duration; 57.0% and 86.9% of dual users were not satisfied with their sleep and have insufficient sleep duration, respectively. The proportion of students who were not satisfied with their sleep was higher among cigarette-only users compared to e-cigarette-only users (52.7% vs. 45.8%), but the two groups reported similar rates of insufficient sleep duration (84.2% vs. 84.3%). Compared to non-users, cigarette-only users, e-cigarette-only users, and dual users were more likely to not be satisfied with sleep (odds ratios [ORs] were 1.49, 1.36, and 1.75, respectively) and had significantly higher odds of experiencing insufficient sleep duration (ORs were 1.85, 2.06, and 2.34, respectively). CONCLUSION: E-cigarette-only use and dual use as well as cigarette-only use were associated with poor sleep health. Therefore, to improve adolescent sleep health, health professionals should provide sleep intervention strategies considering the association between smoking and sleep health.

Enhancement of Wound Healing Efficacy by Increasing the Stability and Skin-Penetrating Property of bFGF Using 30Kc19α-Based Fusion Protein.

The instability of recombinant basic fibroblast growth factor (bFGF) is a major disadvantage for its therapeutic use and means frequent applications to cells or tissues are required for sustained effects. Originating from silkworm hemolymph, 30Kc19α is a cell-penetrating protein that also has protein stabilization properties. Herein, it is investigated whether fusing 30Kc19α to bFGF can enhance the stability and skin penetration properties of bFGF, which may consequently increase its therapeutic efficacy. The fusion of 30Kc19α to bFGF protein increases protein stability, as confirmed by ELISA. 30Kc19α-bFGF also retains the biological activity of bFGF as it facilitates the migration and proliferation of fibroblasts and angiogenesis of endothelial cells. It is discovered that 30Kc19α can improve the transdermal delivery of a small molecular fluorophore through the skin of hairless mice. Importantly, it increases the accumulation of bFGF and further facilitates its translocation into the skin through follicular routes. Finally, when applied to a skin wound model in vivo, 30Kc19α-bFGF penetrates the dermis layer effectively, which promotes cell proliferation, tissue granulation, angiogenesis, and tissue remodeling. Consequently, the findings suggest that 30Kc19α improves the therapeutic functionalities of bFGF, and would be useful as a protein stabilizer and/or a delivery vehicle in therapeutic applications.

Defatted Tenebrio molitor Larva Fermentation Extract Modifies Steatosis, Inflammation and Intestinal Microflora in Chronic Alcohol-Fed Rats.

This study examined the effects of defatted mealworm fermentation extract (MWF) on alcoholic liver injury in rats. The rats were fed either a Lieber-DeCarli control (Con) or alcohol liquid diet (EtOH). The alcohol-fed rats were administered MWF (50, 100, or 200 mg/kg/day) and silymarin (200 mg/kg/day) orally for eight weeks. MWF prevented alcohol-induced hepatocellular damage by decreasing their serum aspartate transaminase, alanine transaminase, and gamma-glutamyl transpeptidase levels significantly compared to the EtOH group. MWF effectively reduced the relative hepatic weight, lipid contents, and fat deposition, along with the down-regulation of transcriptional factors and genes involved in lipogenesis compared to the EtOH group. It also enhanced the antioxidant defense system by elevating the glutathione level and glutathione reductase activity. MWF attenuated the alcohol-induced inflammatory response by down-regulating hepatic inflammation-associated proteins expression, such as phosphorylated-inhibitor of nuclear factor-kappa B-alpha and tumor necrosis factor-alpha, in chronic alcohol-fed rats. Furthermore, sequencing analysis in the colonic microbiota showed that MWF tended to increase Lactobacillus johnsonii reduced by chronic alcohol consumption. These findings suggest that MWF can attenuate alcoholic liver injury by regulating the lipogenic and inflammatory pathway and antioxidant defense system, as well as by partially altering the microbial composition.

Protective Effects of Methoxsalen Supplementation on Chronic Alcohol-Induced Osteopenia and Steatosis in Rats.

Osteopenia or osteoporosis occurs frequently in alcoholics and patients with alcoholic fatty liver disease. Methoxsalen (MTS), 8-methoxypsoralen, improved osteoporosis in ovariectomized and diabetic mouse models; however, its effects on alcohol-induced osteopenia and steatosis have not been reported. This study examined the effects of MTS on alcohol-induced bone loss and steatosis. Rats in the alcohol groups were fed a Liber-DeCarli liquid diet containing 36% of its calories as alcohol. MTS was at 0.005% in their diet, while alendronate (positive control; 500 µg/kg BW/day) was administered orally for eight weeks. The pair-fed group received the same volume of isocaloric liquid diet containing dextrin-maltose instead of alcohol as the alcohol control group consumed the previous day. In the alcohol-fed rats, the MTS and alendronate increased the bone volume density, bone surface density and trabecular number, while the bone specific surface, trabecular separation and structure model index were decreased in the tibia. MTS down-regulated tibial tartrate-resistant acid phosphatase 5 (TRAP) expression compared to the alcohol control group. MTS or alendronate prevented chronic alcohol-induced hepatic lipid accumulation and the triglyceride level in the alcohol-fed rats by decreasing the lipogenic enzyme activities and increasing the fatty acid oxidation enzyme activities. MTS reduced significantly the serum levels of alcohol, TRAP and tumor necrosis factor-α compared to the alcohol control group. Overall, these results suggest that MTS is likely to be an alternative agent for alcoholic osteopenia and hepatosteatosis.