Hepatoprotective effects of paeonol by suppressing hepatic stellate cell activation via inhibition of SMAD2/3 and STAT3 pathways.

Hepatic stellate cell (HSC) activation is a key event in extracellular matrix accumulation, causing hepatic fibrosis. Therefore, identifying chemicals that inhibit HSC activation is an important therapeutic strategy for hepatic fibrosis. The aim of this study was to investigate the therapeutic effects of paeonol on HSC activation. In LX-2 cells, paeonol inhibited the expression of collagen and decreased the expression of HSC activation markers. In mice with thioacetamide-induced liver fibrosis, paeonol treatment decreased the serum levels of aspartate aminotransferase and alanine transaminase and mRNA expression of α-smooth muscle actin, platelet-derived growth factor-ß, and connective-tissue growth factor. Investigation of the underlying molecular mechanism of paeonol showed that paeonol inhibits the SMAD2/3 and STAT3 signaling pathways that are important for HSC activation. On the basis of these results, paeonol should be investigated and developed further for hepatic fibrosis treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01440-9.

Nudging Public Health Behaviors to Prevent COVID-19: A Systematic Review.

Many countries have implemented strict preventive measures and mandatory policies to curb virus transmission during the COVID-19 pandemic. Some have adopted softer approaches, such as nudge-based intervention, to influence public health behavior. This systematic review, conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines, aims to determine if the nudge-based intervention can effectively influence people's preventive behavior during the early period of the COVID-19 pandemic. The review indicated an overall positive outcome, but results were mixed as nudge-based interventions substantially depended on the situational context. While the review found that the nudging technique that presents and conveys decision-related information was essential to nudging people, a secondary nudge would often applied to deliver the interventions. In addition, there was no indication of an ideal nudge technique that would be effective in most situations. Conversely, our findings indicate that the nudge would likely suffer from habituation after repeated intervention or backfire due to inappropriate use of nudges. Also, the ceiling effect would inhibit any nudge influences regardless of the technique(s) used. In sum, the results and the applicability of nudge-based interventions were mixed, highlighting the need for further research to advance the theory and practical developments.

Protective effect of gomisin N on benzyl butyl phthalate-induced dysfunction of testosterone production in TM3 Leydig cells.

BACKGROUND: Exposure to benzyl butyl phthalate (BBP) may induce disorders in the male reproductive system. However, the molecular mechanisms remain unknown. Here we investigated the effect of BBP on testosterone production and its molecular mechanisms. Furthermore, we also investigated the role of gomisin N (GN) from Schisandra chinensis (S. chinensis) in testosterone synthesis in TM3 Leydig cells. METHOD AND RESULTS: First, we examined the effects of BBP on expression levels of testosterone biosynthesis-related genes (StAR, CYP11α1, CYP17α1, 3ßHSD, and 17ßHSD) and attenuation-related genes (CYP1ß1, CYP19α1, and Srd5α1-3). Although testosterone biosynthesis-related genes did not change, attenuation-related genes such as CYP1ß1 and CYP19α1 were upregulated with ROS generation and testosterone level attenuation in the presence of 50 µM of BBP. However, the compound with the highest ROS and ONOO- scavenging activity from S. chinensis, GN, significantly reversed the expression of BBP-induced testosterone attenuation-related gene to normal levels. Subsequently, GN improved the testosterone production levels in TM3 Leydig cells. These events may be regulated by the antioxidant effect of GN. CONCLUSIONS: On conclusion, our study suggests, for the first time, that BBP impairs testosterone synthesis by the modulation of CYP1ß1 and CYP19α1 expression in TM3 cells; GN could potentially minimize the BBP-induced dysfunction of TM3 cells to produce testosterone by suppressing CYP19α1 expression.

Extending the Knowledge Gap Hypothesis to Narrative Persuasion: Parents' Information-Seeking Intention and Learning About Adolescent Children's Covid-19 Vaccination.

The gap in knowledge and information-seeking between high and low socioeconomic status (SES) has been well documented. This study extends this knowledge gap hypothesis to narrative persuasion in the context of parents' knowledge and information-seeking intention concerning adolescents' COVID-19 vaccination. It specifically tests if the gap is moderated by a message type (narrative vs. non-narrative). An online quasi-experiment, with a 2 (participants' education level: high vs. low) × 3 (message type: narrative vs. non-narrative vs. no-message) between-subject design, showed a main effect of education level (i.e., parents with a higher [vs. lower] education level rated a higher intention to seek information and provided more correct answers on questions about adolescents' COVID-19 vaccination) and an interaction between the two factors. The interaction showed that the gap between high- and low-education groups in information-seeking intention disappeared among those who read the narrative or non-narrative, and the gap in knowledge disappeared among those who read the narrative. Study findings suggest the utility of narratives in narrowing the gap in knowledge and information-seeking to improve parents' decisions on child vaccination.

Cultural tightness-looseness and normative social influence in eight Asian countries: Associations of individual and collective norms with vaccination intentions.

RATIONALE: Countries worldwide faced the same public health crisis that required promoting the same health behavior-vaccinations-during the COVID-19 pandemic. Thus, scholars have a unique opportunity to test behavioral change theories across countries with different cultural backgrounds. OBJECTIVE: Employing the extended theory of social normative behavior, this study examines the influence of individual and collective norms on COVID-19 vaccination intention across eight Asian countries. We examine how cultural tightness-looseness, defined as the degree of a culture's emphasis on norms and tolerance of deviant behavior, shapes normative social influence on COVID-19 vaccination intention. METHODS: We conducted a multicountry online survey (N = 2676) of unvaccinated individuals in China, Indonesia, Japan, Malaysia, Singapore, South Korea, Thailand, and Vietnam in May and June 2021, when COVID-19 vaccination mandates had not yet been implemented in those countries. We conducted hierarchical regression analyses with interaction terms for the total sample and then re-categorizied the eight countries as either "tight" (n = 1102) or "loose" (n = 1574) to examine three-way interactions between individual norms, collective norms, and cultural tightness-looseness. RESULTS: Perceived injunctive norms exerted the strongest impact of all normative factors on vaccination intention. Collective injunctive norms' influence depended on both perceived injunctive and descriptive norms, which was larger when norms were lower (vs. higher). The interactive pattern between perceived and collective norms was more pronounced in countries with greater cultural tightness. CONCLUSION: Our findings reveal nuanced patterns of how individual and collective social norms influence health behavioral decisions, depending on the degree of cultural tightness-looseness.

Combined Treatment of Mori folium and Mori Cortex Radicis Ameliorate Obesity in Mice via UCP-1 in Brown Adipocytes.

Mori Folium (Morus alba leaf, MF) and Mori Cortex Radicis (Morus alba root cortex, MR) have been studied for their anti-obesity effects by enhancing the browning process and inhibiting adipogenesis. However, important aspects of their protective mechanisms have not been thoroughly investigated, which could aid in developing functional food. Thus, this study aims to determine the synergistic effects of MF and MR against obesity and its associated mechanisms. In an in vitro cell culture model of brown adipocytes, a 1:1 mixture of MF and MR showed a synergistic effect on the expression of brown adipocyte-specific genes, including Ucp-1, Ppargc1a, Cbp/p300-interacting transactivator (Cited), Prdm16, Tbx1, and Fgf21 compared with either MF- or MR-treated conditions. Moreover, they demonstrated the involvement of cAMP and Ca2+ in induction of brown adipocyte-specific genes. In an in vivo model using HFD-fed mice, MF/MR significantly inhibited weight gain, plasma cholesterol, LDL, TG content, fat mass, and adipocyte size. Furthermore, MF/MR inhibited morphological alteration and the expressions of fatty acid synthesis genes such as Srebp1 and Fasn in the white adipose tissue. Thermogenesis genes were recovered in the brown adipose tissue with MF/MR supplementation, indicating that MF/MR regulated adipocytic dysmetabolism where AMPK signaling is involved. In conclusion, these results suggested that MF/MR regulates brown and beige adipocyte processes, providing one of the preventive functional food/herbal medicines against obesity and its associated metabolic diseases.

Combination of Panax ginseng and Diospyros kaki Leaf Inhibits White Adipocyte Differentiation and Browning Process through AMP-Activated Protein Kinase (AMPK) Activation In Vitro and In Vivo.

Activating brown adipose tissue (BAT) and stimulating white adipose tissue (WAT) browning is a prospective obesity treatment method. Dietary components derived from plants are the most effective approach to activate BAT and promote WAT browning in rodents. This study investigated the synergistic effects of Panax ginseng (PG) and Diospyros kaki leaf (DKL) extract on adipocyte differentiation and browning, as well as the molecular mechanism underlying their beneficial effects. The administration of PG and DKL to HFD-induced obese mice significantly decreased body weight and epididymal and abdominal adipose tissue mass. In in vitro, PG inhibited the adipogenesis of 3T3-L1 adipocytes by regulating the expression of key adipogenic regulators, such as peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)-α. In contrast, DKL negligibly influenced the adipogenesis of 3T3-L1 adipocytes but greatly increased the protein expression of UCP-1, PGC-1α, and PPARα in BAT and/or WAT. Moreover, PG and DKL inhibited adipogenesis synergistically and activated white adipocyte browning via AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) pathways. These results suggest that a combination of PG and DKL regulates adipogenesis in white adipocytes and browning in brown adipocytes by activating AMPK/SIRT1 axis. The potential use of PG and DKL may represent an important strategy in obesity management that will be safer and more effective.

Biological Activity and Component Analyses of Chamaecyparis obtusa Leaf Extract: Evaluation of Antiwrinkle and Cell Protection Effects in UVA-Irradiated Cells.

Background and Objectives: Chamaecyparis obtusa (C. obtuse) extract has been used as a folk medicinal remedy in East Asian countries to alleviate inflammation and prevent allergies. Active oxygen causes skin aging and leads to skin cell and tissue damage. Extensive research has been conducted to control active oxygen generation to prevent skin aging. We evaluated the antioxidant activity and antiwrinkle effect of C. obtusa extract to determine its potential as a cosmetic material. Materials and Methods: The antioxidant activity of a 70% ethanol extract of C. obtusa (COE 70) and a water extract of C. obtusa (COW) was determined using 2,2-diphenyl-1-picrylhydrazy (DPPH) scavenging, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) scavenging, superoxide dismutase-like activity, xanthine oxidase inhibition, and ferric-reducing antioxidant power assays. The effective concentration of the extracts was determined using the methyl thiazolyl tetrazolium assay to evaluate their toxicity. The effects of COE 70 on the production of matrix metalloproteinases (MMPs) and procollagen, and expression of activated cytokines, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), in UVA-irradiated fibroblasts were determined using quantitative real-time PCR. Additionally, quercitrin, amentoflavone, hinokiflavone, and myricetin concentrations in COE 70 were determined using high-pressure high-performance liquid chromatography. Results: COE 70 had higher polyphenol and flavonoid concentrations than COW and exhibited an excellent antioxidant effect. COE 70 suppressed UVA-induced fibroblast death by 21.3% at 25 µg/mL. It also increased MMP-1, MMP-3, TNF-α, and IL-6 mRNA levels at 5-25 µg/mL compared with those in control UVA-irradiated fibroblasts. Moreover, mRNA levels of collagen type I and superoxide dismutase significantly increased, indicating the antiwrinkle and anti-inflammatory effects of the extract. Among the COE 70 components, quercitrin concentration was the highest; hence, quercitrin could be an active ingredient. Conclusions: COE 70 could be used as a natural antioxidant and antiwrinkle agent.

Advanced Practice Nurses' Organization Commitment: Impact of Job Environment, Job Satisfaction, and Person-Organization Fit.

PURPOSE: The demand for advanced practice nurses (APNs) has increased globally due to a shortage of physicians and an increased demand for high-quality healthcare. Research is needed on the enhancement of advanced practice nurses' organization commitment. Organization commitment (OC) directly impacts the retention of APNs. This study aims to identify the key factors affecting the OC of advanced practice nurses. METHOD: A cross-sectional survey was conducted at the largest hospital in South Korea. A total of 189 APNs answered survey questions. A partial least squares-structural equation modeling method was employed to analyze the survey responses. RESULTS: A pay scale of APNs is positively associated with person-organization fit (POF). However, the effect of job location and computer self-efficacy on POF is not significant. Job satisfaction plays a salient direct role in supervision and POF. Job satisfaction is also a significant moderator in the relationship between supervision and POF. POF is significantly associated with both OC and supervision. Supervision has a positive effect on organization commitment. CONCLUSIONS: Pay scale, job satisfaction, supervision, and POF are significant factors affecting organization commitment. Establishing an intra-organization entity, such as APN steering committee, to ensure mutual consensus and transparent communication between administrators and APNs would enhance POF, the rating of supervision, and organization commitment.

Profile identification and characterization of risk perceptions and preventive behaviors during the COVID-19 pandemic: A latent profile analysis.

In a public health crisis, communication plays a vital role in making sure policies and recommendations from the government level get disseminated accurately to its people and is only considered as effective when the public accepts, supports, complies to, and engages in policies or behaves as per governments' recommendations. Adopting the multivariate audience segmentation strategy for health communication, this study uses a data-driven analytical method to (1) identify audience segments of public health crisis communication in Singapore based on knowledge, risk perception, emotional responses, and preventive behaviors; and (2) characterize each audience segment according to demographic factors, personality traits, information processing styles, and health information preferences. Results (N = 2033) from a web-based questionnaire executed in August 2021 have identified three audience segments: the less-concerned (n = 650), the risk-anxious (n = 142), and the risk-majority (n = 1,241). This study offers insights to how audiences of public health crisis communication perceive, process, and respond to information directed to them during the pandemic, thereby informing policy makers to tailor more targeted public health communication interventions in promoting positive attitude and behavior change.

Schisandrol A and gomisin N from Schisandra chinensis extract improve hypogonadism via anti-oxidative stress in TM3 Leydig cells.

BACKGROUND/OBJECTIVES: Male hypogonadism is a condition where the body does not produce enough testosterone and significantly impacts health. Age, obesity, genetics, and oxidative stress are some physiological factors that may contribute to testosterone deficiency. Previous studies have shown many pharmacological benefits of Schisandra chinensis (S. chinensis) Baillon as an anti-inflammatory and antioxidant. However, the molecular mechanism of attenuating hypogonadism is yet to be well established. This research was undertaken to study the effects of S. chinensis extract (SCE) on testosterone deficiency. MATERIALS/METHODS: S. chinensis fruit was pulverized and extracted using 60% aqueous ethanol. HPLC analysis was performed to analyze and quantify the lignans of the SCE. RESULTS: The 2,2-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays confirmed that the SCE and its major lignans (schisandrol A and gomisin N) inhibit oxidative stress. Effects of SCE analysis on the testosterone level under oxidative stress conditions revealed that both schisandrol A and gomisin N were able to recover the lowered testosterone levels. Through mRNA expression of TM3 Leydig cell, we observed that the SCE lignans were able to induce the enzymes involved in testosterone biosynthesis-related genes such as 3ß-HSD4 (P < 0.01 for SCE, and P < 0.001 for schisandrol A and gomisin N), 17ß-HSD3 (P < 0.001 for SCE, schisandrol A and gomisin N), and 17, 20-desmolase (P < 0.01 for schisandrol A, and P < 0.001 for SCE and gomisin N). CONCLUSIONS: These results support that SCE and its active components could be potential therapeutic agents for regulating and increasing testosterone production.

Can Press Freedom Enhance the Effect of News Exposure on COVID-19 Health Beliefs? A Health Belief Model Perspective.

News media can influence citizens' health beliefs about COVID-19 and eventually their vaccination intention. However, existing literature has rarely investigated how such effect is contingent upon a country-level factor: press freedom. Situated in the Health Belief Model, this study draws upon a multi-national survey (N = 3,599), involving 10 major cities in Asia to address the research gap. Results showed that news exposure has a positive effect on personal health beliefs on COVID-19, affecting their vaccination intention. More interestingly, the relationship between news exposure and personal health beliefs about COVID-19 was negatively moderated by level of press freedom - that is, the relationship between news exposure and personal health beliefs is stronger in cities that belong to countries with low levels of press freedom.

Avoiding real news, believing in fake news? Investigating pathways from information overload to misbelief.

This study sought to examine the potential role of news avoidance in belief in COVID-19 misinformation. Using two-wave panel survey data in Singapore, we found that information overload is associated with news fatigue as well as with difficulty in analyzing information. News fatigue and analysis paralysis also subsequently led to news avoidance, which increased belief in COVID-19 misinformation. However, this link is present only among those who are frequently exposed to misinformation about COVID-19.

Schisandrin C: an active compound from the fruit of Schisandra chinensis in anti-inflammation and anti-oxidation.

Inflammatory responses are involved in various diseases, such as insulin resistance, atherosclerosis, and hypogonadism. This study investigates the effects of SCE on anti-inflammation and molecular mechanisms in LPS-induced macrophages. RAW 264.7 macrophage cells were treated with LPS for 24 hr, followed by SCE, schisandrin C (Sch C) (1, 10, and 100 µM), and gomisin N (GN) (1, 10, and 100 µM) for 24 hr. Gene expression levels of pro-inflammatory cytokines were measured by qPCR. Protein expression of NLPR3 inflammasome was examined by western blot analysis. The expression levels of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNFα, were significantly reduced after SCE treatment. Sch C significantly inhibits these pro-inflammatory cytokines, while GN suppresses only IL6. Furthermore, Sch C significantly prevented the activation of NLRP3 inflammasome complexes such as NLRP3 and caspase-1. Sch C is the major active compound of SCE on anti-inflammation through attenuation of NLRP3 inflammasome.

Multilevel causal attributions on transboundary risk: Effects on attributions of responsibility, psychological distance, and policy support.

This study used two randomized experiments in a prospective design (Study 1 N = 297, Study 2 N = 296) to examine how multilevel causal attribution dimensions (internal vs. external to an individual or a country) shape domestic and foreign policy support to counter transboundary risk. Results from Study 1 and 2 showed that external-country (vs. internal-country) causal attribution reduced perceptions of internal-country attributions of responsibility, which had a cross-lagged effect on support for domestic-industry policies to mitigate the risk. In contrast, perceptions of external-country attributions of responsibility increased support for foreign policies in a 2-week follow up. This study offers theoretical insights into the demarcation of multilevel causal attribution dimensions in studying media framing effects. It also highlights some important causal mechanisms of how media frames shape public support for policies aimed at transboundary risk mitigation.

Chemokine receptor CCR9 suppresses the differentiation of CD4+CD8αα+ intraepithelial T cells in the gut.

The chemokine receptor CCR9 equips T cells with the ability to respond to CCL25, a chemokine that is highly expressed in the thymus and the small intestine (SI). Notably, CCR9 is mostly expressed on CD8 but not on CD4 lineage T cells, thus imposing distinct tissue tropism on CD4 and CD8 T cells. The molecular basis and the consequences for such a dichotomy, however, have not been fully examined and explained. Here, we demonstrate that the forced expression of CCR9 interferes with the tissue trafficking and differentiation of CD4 T cells in SI intraepithelial tissues. While CCR9 overexpression did not alter CD4 T cell generation in the thymus, the forced expression of CCR9 was detrimental for the proper tissue distribution of CD4 T cells in the periphery, and strikingly also for their terminal differentiation in the gut epithelium. Specifically, the differentiation of SI epithelial CD4 T cells into immunoregulatory CD4+CD8αα+ T cells was impaired by overexpression of CCR9 and conversely increased by the genetic deletion of CCR9. Collectively, our results reveal a previously unappreciated role for CCR9 in the tissue homeostasis and effector function of CD4 T cells in the gut.

[Effects of the Advanced Practice Nurse-Led Psychoeducational Program for Colorectal Cancer Survivors].

PURPOSE: This study aimed to investigate the effects of an advanced practice nurse-led psychoeducational program on distress, anxiety, depression, coping with cancer (CWC), health promotion behavior (HPB), and quality of life (QOL) among colorectal cancer survivors. METHODS: This study was designed as a quasi-experimental study with a non-equivalent control group pretest-posttest. The participants were survivors of colorectal cancer who underwent follow-up care. There were 39 survivors: 19 in the experimental group and 20 in the control group. The experimental group performed a psychoeducational program for 120 minutes per session, once a week for a total of six weeks, while the control group received routine education and counseling. Distress, anxiety, depression, CWC, HPB, and QOL were investigated before, immediately after, and 4 weeks after the intervention. The data were analyzed with SPSS/WIN ver. 24.0, using repeated measures ANOVA. RESULTS: There were significant interactions between time and group for distress and anxiety. In addition, CWC interacted with the total of CWC and interpersonal coping, and QOL interacted with the total of QOL and functional status. However, there were no significant differences in the depression or HPB scores. CONCLUSION: Based on the results of this study, we expect that this program can be used as an effective intervention for colorectal cancer survivors.

Dual function of a bumblebee (Bombus ignitus) serine protease inhibitor that acts as a microbicidal peptide and anti-fibrinolytic venom toxin.

In bee venoms, low-molecular-weight peptides, including serine protease inhibitors (SPIs), exhibit multifunctional activities. Although SPIs in bee venoms are relatively well known, those that function in both the body and secreted venom of bees are not well-characterized. In this study, we identified a bumblebee (Bombus ignitus) SPI (BiSPI) that displays microbicidal and anti-fibrinolytic activities. BiSPI was found to consist of a trypsin inhibitor-like domain containing a P1 site and ten cysteine residues. We observed that the BiSPI gene was ubiquitously transcribed in the body, including the venom glands. In correlation, the BiSPI protein was detected both in the body and secreted venom by using an antibody against a recombinant BiSPI peptide produced in baculovirus-infected insect cells. Recombinant BiSPI exhibited inhibitory activity against trypsin but not chymotrypsin and inhibited microbial serine proteases and plasmin but not elastase or thrombin. Moreover, recombinant BiSPI recognized carbohydrates and bound to fungi and gram-negative and gram-positive bacteria. Consistent with these properties, recombinant BiSPI exhibited microbicidal activities against bacteria and fungi through induction of structural damage by binding to the microbial surfaces. Additionally, recombinant BiSPI inhibited the plasmin-mediated degradation of human fibrin and was thus concluded to exhibit anti-fibrinolytic activity. Moreover, the peptide showed no effect on hemolysis. These findings demonstrate the dual function of BiSPI, which acts as a microbicidal peptide and anti-fibrinolytic venom toxin.

Rubus occidentalis and Ellagic Acid Affect the Contractility of Penile Corpus Cavernosum Smooth Muscle through the Nitric Oxide-Cyclic Guanosine Monophosphate and Cyclic Adenosine 3',5'-Monophosphate Signaling Pathway.

The present study was designed to evaluate the relaxation effect of Rubus occidentalis (RO) and ellagic acid (EA) on rabbit penile corpus cavernosum smooth muscle (PCCSM). Rabbit PCCSM was treated with ROE or EA after preincubation with nitric oxide synthase (NOS), guanylate cyclase (GC), adenylyl cyclase (AC) or protein kinase A (PKA) blocker. Cyclic nucleotides in the perfusate were analyzed using radioimmunoassay (RIA). Subsequently, perfused PCCSMs were subjected to analysis to evaluate the expression level of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS). The interaction of ROE or EA with phosphodiesterase (PDE) 5 and PDE4 inhibitors, such as udenafil (UDE) and rolipram (ROL), were also evaluated. Both ROE and EA relaxed the PCCSM in a concentration-dependent manner. Coincubation of ROE or EA with NOS, GC, AC, or PKA blocker significantly decreased the ROE- and EA-induced relaxation. Pretreatment of ROE and EA significantly upregulated the cyclic guanosine monophosphate (cGMP), cyclic adenosine 3',5'-monophosphate (cAMP), and eNOS levels in the perfused PCCSM. Furthermore, the treatment of ROE and EA markedly increased the UDE- and ROL-induced relaxation of the PCCSM. In conclusion, ROE and EA induced PCCSM relaxation by activating the nitric oxide (NO)-cGMp and cAMp signaling pathways and may have a synergistic action to improve erectile function.