• The interaction between ferroptosis and myocardial ischemia-reperfusion injury: molecular mechanisms and potential therapeutic targets.
    3 months ago
    Myocardial ischemia-reperfusion injury (MIRI) is a common fatal event in cardiovascular diseases. Oxidative stress, energy metabolism disorders, and inflammatory responses that occur during this process cause severe damage to myocardial cells. Ferroptosis is a novel form of cell death closely related to cellular damage in MIRI. Numerous studies have demonstrated that specific active ingredients can regulate iron homeostasis and inhibit ferroptosis, thereby protecting myocardial function and enhancing the prognosis of patients. At the same time, traditional Chinese medicine monomers also provide a new perspective for the treatment of MIRI. This review summarizes the recent advances in understanding the mechanisms underlying ferroptosis, with the aim of providing potential novel therapeutic strategies for the clinical management of MIRI.
    Cardiovascular diseases
    Care/Management
  • Cardiomyocyte-specific knockout of Oip5-as1 exacerbates MI/R-induced ferroptosis via p62/KEAP1/NRF2 inhibition.
    3 months ago
    Myocardial ischemia/reperfusion (MI/R) injury is a major cause of adverse outcomes after acute myocardial infarction. Ferroptosis is an iron-dependent and lipid-peroxidation-driven form of cell death implicated in this injury. However, the regulatory role of long non-coding RNAs (lncRNAs) in this process remains unclear. Here, we investigated whether the lncRNA OIP5 antisense RNA 1 (Oip5-as1) modulates ferroptosis during MI/R. A cardiomyocyte-specific Oip5-as1 knockout mouse was generated using CRISPR/Cas9 technology combined with the Cre-LoxP system. Isolated hearts were then exposed to MI/R in a Langendorff perfusion apparatus. Compared with floxed controls, Oip5-as1-deficient hearts exhibited impaired hemodynamic parameters, larger infarcts, more severe histopathological damage, and marked mitochondrial disruption, as determined by Langendorff system analysis, triphenyltetrazolium chloride staining, hematoxylin-eosin staining, and transmission electron microscopy, respectively. These structural and functional deficits were accompanied by elevated ferrous iron levels, increased lipid peroxidation, reduced antioxidant capacity, upregulation of the ferroptosis driver ACSL4, and downregulation of the ferroptosis suppressors FTH1, SLC7A11, and GPX4. Administration of the selective ferroptosis inhibitor Ferrostatin-1 restored antioxidant capacity, normalized the expression of ferroptosis-related proteins, and significantly reduced infarct size and cardiac functional impairment in Oip5-as1-deficient hearts. Mechanistic analyses revealed that Oip5-as1 deletion suppressed the p62/KEAP1/NRF2 signaling pathway, whereas disruption of KEAP1-NRF2 binding with KI696 reactivated NRF2 signaling and reinstated resistance to ferroptosis. Collectively, these findings demonstrate that Oip5-as1 limits MI/R injury by sustaining p62/KEAP1/NRF2-mediated suppression of ferroptosis. Furthermore, Oip5-as1 is identified as a promising therapeutic target for cardioprotection.
    Cardiovascular diseases
    Care/Management
  • AIE-ESIPT synergistic fluorescence probe for superoxide and hypochlorite using acetoxy-substituted tetraphenyl imidazole.
    3 months ago
    Reactive oxygen species (ROS) are highly reactive molecules that play pivotal roles in various cellular functions such as signaling, immune responses, and metabolic regulation. While they are essential in normal physiological processes, excessive ROS accumulation leads to oxidative stress, which damages cellular structures, including lipids, proteins, and DNA, contributing to diseases like cancer, neurodegeneration, and cardiovascular disorders. Therefore, the development of effective detection strategy for the selective detection of ROS, particularly superoxide (O2•-) and hypochlorite (ClO-), is crucial for understanding their roles in cellular processes.

    In this study, we introduce an acetoxy-substituted tetraphenyl imidazole (AcOPI) as a fluorescence probe specifically designed to detect superoxide (O2•-) and hypochlorite (ClO-) through a unique combination of aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT). The probe demonstrates a remarkable 96-fold fluorescence enhancement upon ROS exposure, with a large Stokes shift (Δλ = 145 nm) that minimizes interference from background fluorescence. Additionally, AcOPI exhibits low self-quenching and high aqueous compatibility, which are advantageous features for its application in biological systems. These properties make AcOPI a highly sensitive and selective tool for ROS detection in aqueous environments. These results could be applied to follow-up research focused on developing fluorescence probes that absorb and emit detectable visible light for spatiotemporal and real-time detection in living systems.

    The successful development of AcOPI as a fluorescent probe for detecting superoxide and hypochlorite offers a promising strategy for monitoring ROS under both physiological and environmental conditions. Owing to its high sensitivity, large Stokes shift, and excellent aqueous compatibility, AcOPI enables real-time ROS imaging and detection, underscoring its potential for diagnostic applications in ROS-related diseases. This study further suggests a potential application in elucidating the link between chronic inflammation and cancer by exploring the mechanisms of ROS interactions during disease progression. Applying our methodology to chronic inflammation models may help clarify the integrated ROS signaling pathways involved in tumor development. Beyond its medical relevance, AcOPI also shows strong potential for environmental monitoring of aquatic organisms subjected to oxidative stress induced by pollutants such as heavy metals, pesticides, and disinfectants. Although AcOPI demonstrated promising performance in aqueous systems, several challenges remain for in vivo applications. The limited tissue penetration of visible light may restrict the use of these probes for deep-tissue imaging or targeted delivery.
    Cardiovascular diseases
    Policy
  • Biosynthesis-based metabolomics analysis reveals chemical diversity between two Salvia species.
    3 months ago
    Salvia officinalis is an important dietary supplement that is widely used as a flavor regulator and plays an important role in the prevention and treatment of neurodegenerative diseases. Salvia miltiorrhiza Bunge is a famous Chinese herbal medicine for treating cardiovascular diseases. Secondary metabolites with diverse structures endow the two species with various edible and medicinal values. However, the differences in secondary metabolites between the leaves of S. officinalis and S. miltiorrhiza are still unclear. Herein, FlavourSpec® combined with spatial metabolomics was used to explore the distribution patterns of secondary metabolites including volatile and non-volatile components. The results indicated that the chemical compositions of the two Salvia species were significantly different. Specifically, S. miltiorrhiza Bunge contained high levels of phenolic acid components with a furan ring that can hardly be detected in S. officinalis. The volatile small molecules as well as carnosic acid and its derivatives were found to be major components of S. officinalis leaves. Because of the long-term exposure of leaves to ultraviolet radiation and the same environmental stress, carnosic acid and its derivatives exhibit widespread distribution characteristics in S. officinalis leaves. The work explored the similarities and differences in secondary metabolites of S. officinalis and S. miltiorrhiza Bunge, providing not only the material basis to develop the application value in dietary nutrition, but also a theoretical foundation for the development and utilization of medicinal resources of Salvia.
    Cardiovascular diseases
    Policy
  • BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis.
    3 months ago
    JKAP regulates T cell immunity and inflammation in autoimmune diseases. This study investigates how bone marrow mesenchymal stem cell (BMSC)-derived exosomes deliver JKAP to restore Th17/Treg balance in rheumatoid arthritis (RA). RA CD4+ T-cells and fibroblast-like synoviocytes (RA-FLS) were treated with BMSC, exosomes, or JKAP-modified exosomes ± AKT/ERK inhibitors. BMSC/exosomes suppressed Th17 and promoted Treg differentiation, effects diminished without exosomes. JKAP knockdown impaired exosome-mediated Th17/Treg regulation and AKT/ERK activation, while overexpression enhanced these effects. JKAP-deficient exosomes increased CD4+ T cell proliferation and RA-FLS inflammation, reversed by AKT/ERK inhibition. In collagen-induced arthritis mice, exosomes alleviated symptoms and restored Th17/Treg balance, whereas JKAP knockdown exacerbated arthritis and disrupted balance. JKAP-overexpressing exosomes showed opposite effects. Thus, BMSC exosomes mitigate RA by delivering JKAP to restore immune balance via AKT/ERK pathways.
    Cardiovascular diseases
    Policy
  • Assessing character strengths in hungary: exploring factor structure and reliability of VIA-IS-M.
    3 months ago
    Character strengths are a prevalent topic of positive psychology research. Recently, the questionnaires suitable for measuring the 24 character strengths (VIA-IS) have been revised. This new version, called VIA-IS-R, has a briefer form, the 96-item VIA-IS-M. Despite the widespread usage and measurement of the character strengths, the revised version of the questionnaire has yet to be utilised in Hungary. Therefore, the study aimed to test and validate the VIA-IS-M questionnaire in the Hungarian context.

    We conducted four online studies on different adult samples, with 1878 participants in total. In addition to character strengths, satisfaction with life, well-being, burnout, and mental health were measured to analyse criterion validity.

    In Study 1, the internal consistency of the scales was low in some cases (Gratitude, Judgment, Kindness). After modification, reliabilities were acceptable in the following studies. Weak-to-moderate correlations were observed between character strengths and criterion variables, consistent with prior expectations. Character strengths were used as predictor variables in the regression models, and they demonstrated sufficient predictive power for all the criterion variables in all studies (R2 = 0.43-71). According to exploratory factor analysis, 3-factor solutions were suitable for the data and aligned with recent studies on character strengths' factor structure.

    Overall, the VIA-IS-M-H demonstrates acceptable reliability and validity levels and is suitable for assessing character strengths in the Hungarian context.
    Mental Health
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    Advocacy
  • Labeling in a California Latinx community: public health implications for youth and role in community narratives.
    3 months ago
    Prior research demonstrates that Latinx youth disproportionately receive negative labels from parents, peers, and teachers. Negative labels are stigmatizing and often result in rejection or devaluation of the labeled person which can be pivotal within the developmental window of adolescence. Prior research has already shown that experiences of exclusion and social rejection can have detrimental impacts on mental and physical health. To this end, it is paramount to understand how labeling is wielded, especially among those most vulnerable, to devise thoughtful solutions. This study examines how labeling is operationalized within a Latinx community and consequences of such labels on health-protective behaviors, wellbeing, peer networks and school engagement.

    In-depth interviews were conducted with 39 adolescents and 20 mothers from a predominantly Latinx and immigrant agricultural community in California. Teams of coders completed iterative rounds of memoing and team meetings to identify themes and develop a code book of inductive and deductive codes. The team completed iterative rounds of coding to refine the codebook and review code discrepancies to ensure fidelity of coding. After coding of mother and adolescent transcripts an additional round of memos and team meetings focused on similarities and differences in youth and mothers' perspectives about labeling.

    Dichotomous labeling of "good" and "bad" arose spontaneously in all mothers and most youth interviews and were pervasive within schools and the broader community. Youth labeled as "bad" experienced limited educational opportunities, exclusion from peers, and community disengagement. While "good kid" labels resulted in educational opportunity and community acceptance these labels also limited health protective-behaviors in some youth, including foregoing contraception. Participants pushed back on negative labeling when it was applied to close family or community acquaintances.

    Targeted interventions that foster social belonging and connection rather than exclusion may facilitate health protective behaviors and have positive implications for future trajectories among youth.
    Mental Health
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  • Eosinophilic esophagitis in children and adolescents: a clinical practice guideline.
    3 months ago
    Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition that affects the esophagus and is marked by the presence of eosinophils. This disease is becoming more common in children and adolescents and can result in symptoms like swallowing difficulties, food impaction and abdominal pain. Managing pediatric EoE requires a team effort including gastroenterologists, allergists and dietitians. Medical treatments may include topical corticosteroids, proton pump inhibitors, and elimination diets. Endoscopy plays a key role in the diagnosis, management and monitoring of the condition. The management of pediatric EoE is distinct from that of adult EoE, due to differences in anatomy, physiology and treatment options. Thus, it is recommended that children with EoE see a pediatric gastroenterologist when possible. However, adult gastroenterologists can also contribute to the management of pediatric EoE when a pediatric gastroenterologist is not accessible. A guideline for the management of pediatric EoE in Italy has been created by Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) to encourage collaboration between adult gastroenterologists and pediatricians, and it has been endorsed by major adult gastroenterology Italian societies including AIGO, SIGE and SIED, highlighting the importance of collaboration in the diagnosis and management of pediatric EoE.
    Mental Health
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  • Implementing twelve-weeks of loving-kindness meditation and mindfulness of breathing for adolescents with nonsuicidal self-injury and their parents: a mixed method pilot study.
    3 months ago
    Psychosocial interventions for adolescents with nonsuicidal self-injury (NSSI) still needs investigation. This study aims to explore the feasibility and preliminary efficacy of twelve weeks of loving-kindness meditation (mettā) and mindfulness of breathing (ānāpānasati) for adolescents with NSSI and their parents.

    This was a prospective, quasi-experimental, mixed-method pilot study with no control group. Twenty-eight adolescents and their parents participated in the twelve weeks of loving-kindness meditation and mindfulness of breathing practice. Self-report questionnaires on NSSI behaviors, depressive symptoms, attachment to parents, and parenting behaviors were administered at baseline, mid-intervention, postintervention, and 3-month follow-up only from the adolescents. Semi-structured interviews about the feasibility of the intervention were conducted with 25 parent-adolescents' dyads at post-intervention.

    A modest dropout of n = 4 (14.2%) was found for adolescents. Nine parents dropouts, with the dropout rate being 33%. The overall satisfaction score of adolescents for the intervention is 4.27 out of 5. Quantitative analysis revealed that there is a significant decrease in adolescents NSSI behavior at postintervention and 3-month follow-up and a significant decrease in adolescents' depressive symptoms at three months follow-up.Qualitative analysis shows that adolescents general has positive attitude toward the intervention, and believe the individual mindfulness practices peaceful but challenging. The experiences in group activity and interactions were rich, but participants failed in persisting the intervention because of multiple obstacles. Attempts to practice mindfulness influenced adolescents' self-injury behavior and also bring positive change in adolescents' emotion. Parents reported increase in emotion regulation and positive change in parenting attitude and behavior. Both adolescents and parents perceived parent-child relationship improvements.

    Twelve weeks of loving-kindness meditation and mindfulness of breathing seems feasible among adolescents with NSSI and their parents. An adequately powered Randomized Controlled Trial (RCT) is needed to examine this intervention's effectiveness for NSSI behavior, emotional symptoms, and family interaction.

    The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200056515) at 7th February 2022.
    Mental Health
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    Care/Management
    Policy
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    Education
  • The roles of loneliness and self-control in the association between social avoidance and nomophobia among college students.
    3 months ago
    Nomophobia has become an increasingly common mental health concern among college students. While prior research has examined various factors contributing to nomophobia, the relationships among social avoidance, loneliness, and self-control within the Chinese context remain underexplored. This study aims to investigate the impact of social avoidance on nomophobia, with a particular focus on the parallel mediating roles of loneliness and self-control. Data were obtained through a survey of 1,008 college students (48% male, n = 484, M = 19.62, SD = 1.88; 52% female, n = 524, M = 20.57, SD = 2.41), and path analysis was used to test the hypotheses. The results revealed that social avoidance significantly predicts nomophobia and that this effect is mediated by both loneliness and self-control. These findings underscore the importance of addressing social avoidance, loneliness, and self-control in efforts to prevent nomophobia. Promoting social engagement may enhance psychological well-being and reduce the risk of nomophobia.
    Mental Health
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