m6A epitranscriptomic modification of inflammation in cardiovascular disease.

Cardiovascular disease is currently the number one cause of death endangering human health. There is currently a large body of research showing that the development of cardiovascular disease and its complications is often accompanied by inflammatory processes. In recent years, epitranscriptional modifications have been shown to be involved in regulating the pathophysiological development of inflammation in cardiovascular diseases, with 6-methyladenine being one of the most common RNA transcriptional modifications. In this review, we link different cardiovascular diseases, including atherosclerosis, heart failure, myocardial infarction, and myocardial ischemia-reperfusion, with inflammation and describe the regulatory processes involved in RNA methylation. Advances in RNA methylation research have revealed the close relationship between the regulation of transcriptome modifications and inflammation in cardiovascular diseases and brought potential therapeutic targets for disease diagnosis and treatment. At the same time, we also discussed different cell aspects. In addition, in the article we also describe the different application aspects and clinical pathways of RNA methylation therapy. In summary, this article reviews the mechanism, regulation and disease treatment effects of m6A modification on inflammation and inflammatory cells in cardiovascular diseases in recent years. We will discuss issues facing the field and new opportunities that may be the focus of future research.

Redox homeostasis in cardiac fibrosis: Focus on metal ion metabolism.

Cardiac fibrosis is a major public health problem worldwide, with high morbidity and mortality, affecting almost all patients with heart disease worldwide. It is characterized by fibroblast activation, abnormal proliferation, excessive deposition, and abnormal distribution of extracellular matrix (ECM) proteins. The maladaptive process of cardiac fibrosis is complex and often involves multiple mechanisms. With the increasing research on cardiac fibrosis, redox has been recognized as an important part of cardiac remodeling, and an imbalance in redox homeostasis can adversely affect the function and structure of the heart. The metabolism of metal ions is essential for life, and abnormal metabolism of metal ions in cells can impair a variety of biochemical processes, especially redox. However, current research on metal ion metabolism is still very limited. This review comprehensively examines the effects of metal ion (iron, copper, calcium, and zinc) metabolism-mediated redox homeostasis on cardiac fibrosis, outlines possible therapeutic interventions, and addresses ongoing challenges in this rapidly evolving field.

m6A epitranscriptomic and epigenetic crosstalk in cardiac fibrosis.

Cardiac fibrosis, a crucial pathological characteristic of various cardiac diseases, presents a significant treatment challenge. It involves the deposition of the extracellular matrix (ECM) and is influenced by genetic and epigenetic factors. Prior investigations have predominantly centered on delineating the substantial influence of epigenetic and epitranscriptomic mechanisms in driving the progression of fibrosis. Recent studies have illuminated additional avenues for modulating the progression of fibrosis, offering potential solutions to the challenging issues surrounding fibrosis treatment. In the context of cardiac fibrosis, an intricate interplay exists between m6A epitranscriptomic and epigenetics. This interplay governs various pathophysiological processes: mitochondrial dysfunction, mitochondrial fission, oxidative stress, autophagy, apoptosis, pyroptosis, ferroptosis, cell fate switching, and cell differentiation, all of which affect the advancement of cardiac fibrosis. In this comprehensive review, we meticulously analyze pertinent studies, emphasizing the interplay between m6A epitranscriptomics and partial epigenetics (including histone modifications and noncoding RNA), aiming to provide novel insights for cardiac fibrosis treatment.

Epigenetic signatures in cardiac fibrosis: Focusing on noncoding RNA regulators as the gatekeepers of cardiac fibroblast identity.

Cardiac fibroblasts play a pivotal role in cardiac fibrosis by transformation of fibroblasts into myofibroblasts, which synthesis and secrete a large number of extracellular matrix proteins. Ultimately, this will lead to cardiac wall stiffness and impaired cardiac performance. The epigenetic regulation and fate reprogramming of cardiac fibroblasts has been advanced considerably in recent decades. Non coding RNAs (microRNAs, lncRNAs, circRNAs) regulate the functions and behaviors of cardiac fibroblasts, including proliferation, migration, phenotypic transformation, inflammation, pyroptosis, apoptosis, autophagy, which can provide the basis for novel targeted therapeutic treatments that abrogate activation and inflammation of cardiac fibroblasts, induce different death pathways in cardiac fibroblasts, or make it sensitive to established pathogenic cells targeted cytotoxic agents and biotherapy. This review summarizes our current knowledge in this field of ncRNAs function in epigenetic regulation and fate determination of cardiac fibroblasts as well as the details of signaling pathways contribute to cardiac fibrosis. Moreover, we will comment on the emerging landscape of lncRNAs and circRNAs function in regulating signal transduction pathways, gene translation processes and post-translational regulation of gene expression in cardiac fibroblast. In the end, the prospect of cardiac fibroblasts targeted therapy for cardiac fibrosis based on ncRNAs is discussed.

Lipid metabolism reprogramming in cardiac fibrosis.

Cardiac fibrosis is a critical pathophysiological process that occurs with diverse types of cardiac injury. Lipids are the most important bioenergy substrates for maintaining optimal heart performance and act as second messengers to transduce signals within cardiac cells. However, lipid metabolism reprogramming is a double-edged sword in the regulation of cardiomyocyte homeostasis and heart function. Moreover, lipids can exert diverse effects on cardiac fibrosis through different signaling pathways. In this review, we provide a brief overview of aberrant cardiac lipid metabolism and recent progress in pharmacological research targeting lipid metabolism alterations in cardiac fibrosis.

Impact of Mobile Apps in Conjunction With Percutaneous Endoscopic Gastrostomy on Patients' Complications, Quality of Life, and Health-Related Self-Care Behaviors: Randomized Clinical Trial.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is commonly chosen for long-term enteral nutrition support. However, common complications of PEG include wound infection, leakage, obstruction, bleeding, dislodgement, pneumonia, peritonitis, and more. The anticipation of these complications by both patients and their family caregivers underscores the essential requirement of ongoing technical guidance for the daily care of PEG and the adoption of preventative strategies. OBJECTIVE: This study aimed to establish and compare a health education program utilizing a tracking system for PEG using a mobile app (PEG app) and instant messaging software versus a paper-based health education program with instant messaging software. Their effectiveness in preventing complications, avoiding hospital readmissions, improving self-care practices, and enhancing quality of life outcomes was assessed. METHODS: A randomized controlled trial design was used, and the study sample consisted of patients from a medical center in central Taiwan who underwent thoracic surgery or gastroenterology procedures. Inclusion criteria were being a new case undergoing his or her first gastric tube insertion and having the ability to operate a smartphone. Exclusion criteria were cases requiring tube replacement or nasogastric tubes. A total of 74 participants were enrolled, with 37 participants in the experimental group and 37 participants in the control group. Data collection took place from hospitalization until 1 month after discharge. The experimental group received care using the gastric tube tracking system (PEG app) and the Line app that included phone, text, and photo capture capabilities, while the control group received routine nursing care and used the Line app. RESULTS: The experimental group demonstrated a significant reduction in the occurrence of complications compared with the control group (χ21=12.087, P=.001). Specifically, the occurrence of leakage events was significantly lower in the experimental group than in the control group (χ21=12.906, P=.001). However, the experimental group exhibited superior self-care ability compared with the control group (t72=2.203, P=.03). There was no significant difference in overall quality of life scores between the experimental and control groups (t72=1.603, P=.11). However, the experimental group showed better social aspects of quality of life than the control group (t72=2.164, P=.03). CONCLUSIONS: Integration of the PEG app with instant messaging can enhance self-care ability, improve social aspects of quality of life, and reduce complications. The study results suggest that the PEG app could be used as an adjunct tool to promote patients' self-directed management of their gastric tube at home, particularly for patients who have undergone their first PEG placement and are being discharged from the hospital. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071271; https://tinyurl.com/4vvy584e.

WTAP boosts lipid oxidation and induces diabetic cardiac fibrosis by enhancing AR methylation.

Dysregulated lipid metabolism occurs in pathological processes characterized by cell proliferation and migration. Nonetheless, the mechanism of increased mitochondrial lipid oxidation is poorly appreciated in diabetic cardiac fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. Herein, increased WTAP expression promotes cardiac fibroblast proliferation and migration, contributing to diabetic cardiac fibrosis. Knockdown of WTAP suppresses mitochondrial lipid oxidation, fibroblast proliferation and migration to ameliorate diabetic cardiac fibrosis. Mechanistically, WTAP-mediated m6A methylation of AR induced its degradation, dependent on YTHDF2. Additionally, AR directly interacts with mitochondrial lipid oxidation enzyme Decr1; overexpression of AR-suppressed Decr1-mediates mitochondrial lipid oxidation, inhibiting cardiac fibroblast proliferation and migration. Knockdown of AR produced the opposite effect. Clinically, increased WTAP and YTHDF2 levels correlate with decreased AR expression in human DCM heart tissue. We describe a mechanism wherein WTAP boosts higher mitochondrial lipid oxidation, cardiac fibroblast proliferation, and migration by enhancing AR methylation in a YTHDF2-dependent manner.

Epigenetic hallmarks in pulmonary fibrosis: New advances and perspectives.

Epigenetics indicates that certain phenotypes of an organism can undergo heritable changes in the absence of changes in the genetic DNA sequence. Many studies have shown that epigenetic patterns play an important role in the lung and lung diseases. Pulmonary fibrosis (PF) is also a type of lung disease. PF is an end-stage change of a large group of lung diseases, characterized by fibroblast proliferation and massive accumulation of extracellular matrix, accompanied by inflammatory injury and histological destruction, that is, structural abnormalities caused by abnormal repair of normal alveolar tissue. It causes loss of lung function in patients with multiple complex diseases, leading to respiratory failure and subsequent death. However, current treatment options for IPF are very limited and no drugs have been shown to significantly prolong the survival of patients. Therefore, based on a systematic understanding of the disease mechanisms of PF, this review integrates the role of epigenetics in the development and course of PF, describes preventive and potential therapeutic targets for PF, and provides a theoretical basis for further exploration of the mechanisms of PF.

Effects of Mindfulness-Based Elder Care (MBEC) on symptoms of depression and anxiety and spiritual well-being of institutionalized seniors with disabilities: a randomized controlled trial.

BACKGROUND: Despite the need to incorporate seniors from various settings into mindfulness-based empirical research, issues of geriatric frailties and non-compliance remain. This study aimed to evaluate the effects of a mindfulness-based elder care (MBEC) program on mental health and spiritual well-being among seniors with disabilities in long-term care residential settings. METHODS: This single-blind, randomized controlled trial (RCT) randomly assigned seventy-seven participants into an MBEC group or control group of an eight-week MBEC program. Participants were assessed every four weeks at baseline (T0), mid-intervention (T1), post-intervention (T2) and follow-up (T3) using the Geriatric Depression Scale Short Form (GDS-SF), the State-Trait Anxiety Inventory (STAI) and the Spiritual Well-Being Scale (SWBS), respectively. RESULTS: Linear mixed model (LMM) showed that MBEC participants' mental health improved significantly after completing the intervention; compared with controls, the MBEC group exhibited significantly lower anxiety (state-anxiety at T2; trait-anxiety at T2 and T3) and fewer depressive symptoms. Spiritual well-being was also significantly enhanced compared to that in the control group. CONCLUSIONS: MBEC has positive effects on both mental health and spiritual well-being outcomes among seniors with disabilities. In long-term care facilities, seniors with abilities have the potential to adhere to and engage in activities of a mindfulness-based intervention. This low risk, easily accessible, and effective 8-week program is recommended to be integrated into regular long-term care institutional routines. TRIAL REGISTRATION: This study was registered with Clinical Trial Registry (ClinicalTrials.gov - U.S. National Library of Medicine #NCT05123261. Retrospectively registered on 07/04/2021.). The CONSORT 2010 guidelines were used in this study for properly reporting how the randomized trial was conducted.

Crosstalk between oxidative stress and epigenetic marks: New roles and therapeutic implications in cardiac fibrosis.

With the in-depth investigation of cardiac fibrosis, oxidative stress (OS) has been recognized as a significant pathophysiological pathway involved in cardiac remodeling and progression. OS is a condition characterized by the disruption of equilibrium between reactive oxygen species (ROS) produced by the organism and the antioxidant defense system, resulting in adverse effects on the structure and function of the heart. The accumulation of reactive substances beyond cellular thresholds disrupts the normal physiology of both cardiomyocytes and non-cardiomyocytes, leading to OS, inflammation, hypertrophy, and cardiac fibrosis. Furthermore, cardiac OS also modulates several crucial genes involved in maintaining cellular homeostasis, including those associated with mitochondrial biogenesis, injury, and antioxidant defense, which are inevitably associated with concurrent epigenetic changes. Multiple studies have demonstrated the crucial role of epigenetic modifications in regulating cardiac OS. Consequently, modulating OS through targeted epigenetic modifications emerges as a potentially promising therapeutic strategy for managing cardiac fibrosis. This article provides a new review of current research on this subject and proposes that epigenetics may improve OS-induced cardiac fibrosis.

Glycolytic reprogramming in organ fibrosis: New dynamics of the epigenetic landscape.

Accumulating evidence has shown that aerobic glycolysis is essential for the establishment and maintenance of the fibrotic phenotype, so treatments targeting glycolytic reprogramming may become an important strategy to reduce fibrosis. Here, we reviewed current evidence on the glycolytic reprogramming in organ fibrosis, new dynamics of the epigenetic landscape. Epigenetic regulation of the expression of specific genes involved mediates glycolytic reprogramming, thereby affecting fibrosis progression. A comprehensive understanding of the interplay between aerobic glycolysis and epigenetics holds great promise for the treatment and intervention of fibrotic diseases. This article aims to comprehensively review the effect of aerobic glycolysis on organ fibrosis, and to elucidate the relevant epigenetic mechanisms of glycolytic reprogramming in different organs.

METTL3 boosts mitochondrial fission and induces cardiac fibrosis by enhancing LncRNA GAS5 methylation.

Dysregulated mitochondrial metabolism occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the role of mitochondrial fission is not well appreciated in cardiac fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. We investigated the causes and consequences of mitochondrial fission in cardiac fibrosis using cultured cells, animal models, and clinical samples. Increased METTL3 expression caused excessive mitochondrial fission, resulting in the proliferation and migration of cardiac fibroblasts that lead to cardiac fibrosis. Knockdown of METTL3 suppressed mitochondrial fission, inhibiting fibroblast proliferation and migration for ameliorating cardiac fibrosis. Elevated METTL3 and N6-methyladenosine (m6A) levels were associated with low expression of long non-coding RNA GAS5. Mechanistically, METTL3-mediated m6A methylation of GAS5 induced its degradation, dependent of YTHDF2. GAS5 could interact with mitochondrial fission marker Drp1 directly; overexpression of GAS5 suppressed Drp1-mediated mitochondrial fission, inhibiting cardiac fibroblast proliferation and migration. Knockdown of GAS5 produced the opposite effect. Clinically, increased METTL3 and YTHDF2 levels corresponded with decreased GAS5 expression, increased m6A mRNA content and mitochondrial fission, and increased cardiac fibrosis in human heart tissue with atrial fibrillation. We describe a novel mechanism wherein METTL3 boosts mitochondrial fission, cardiac fibroblast proliferation, and fibroblast migration: METTL3 catalyzes m6A methylation of GAS5 methylation in a YTHDF2-dependent manner. Our findings provide insight into the development of preventative measures for cardiac fibrosis.

Mitochondrial quality control in cardiac fibrosis: Epigenetic mechanisms and therapeutic strategies.

Cardiac fibrosis (CF) is considered an ultimate common pathway of a wide variety of heart diseases in response to diverse pathological and pathophysiological stimuli. Mitochondria are characterized as isolated organelles with a double-membrane structure, and they primarily contribute to and maintain highly dynamic energy and metabolic networks whose distribution and structure exert potent support for cellular properties and performance. Because the myocardium is a highly oxidative tissue with high energy demands to continuously pump blood, mitochondria are the most abundant organelles within mature cardiomyocytes, accounting for up to one-third of the total cell volume, and play an essential role in maintaining optimal performance of the heart. Mitochondrial quality control (MQC), including mitochondrial fusion, fission, mitophagy, mitochondrial biogenesis, and mitochondrial metabolism and biosynthesis, is crucial machinery that modulates cardiac cells and heart function by maintaining and regulating the morphological structure, function and lifespan of mitochondria. Certain investigations have focused on mitochondrial dynamics, including manipulating and maintaining the dynamic balance of energy demand and nutrient supply, and the resultant findings suggest that changes in mitochondrial morphology and function may contribute to bioenergetic adaptation during cardiac fibrosis and pathological remodeling. In this review, we discuss the function of epigenetic regulation and molecular mechanisms of MQC in the pathogenesis of CF and provide evidence for targeting MQC for CF. Finally, we discuss how these findings can be applied to improve the treatment and prevention of CF.

Effects of a biopsychosocial-spiritual group therapy on quality of life among institutionalized older adults with disabilities: A randomized controlled trial.

The traditional biomedical care approach has been unsatisfactory to meet the complex needs of seniors with long-term multimorbidity and irreversible disability, particularly for those living in residential LTC facilities. This study aimed to develop and evaluate the effectiveness of an 8-week biopsychosocial-spiritual (BPS-S) group intervention with the attempt to enhance quality of life (QoL) and meaning in life among senior residents with disability. This single-blind randomized controlled trail was conducted in eight residential LTC facilities. The primary outcome, 'participants' overall and subdomain QoL', and the secondary outcome, 'meaning in life', were repeatedly assessed, including four time points: before, mid- and post-intervention, and at a 1-month follow-up. A generalized linear mixed model (GLMM) was used to assess between-group differences over time. The post-intervention differences indicated significant higher improvement on senior residents' overall and all 4 domains of QoL, as well as their meaning in life, between the baseline and both times of post-intervention and 1-month follow-up. On the other hand, participants' family QoL have improved immediately in the midst of intervention. This study provides preliminary evidence to support the feasibility and effectiveness of an 8-week BPS-S group therapy. We recommend the BPS-S be integrated into routine institutional care activities to help maximize senior residents' own capacity for self-healing, achieve a state of harmonious balance between body, mind, social and spiritual relationships; and in turn, enhance holistic health of this group.

Reliability and Validity of a Chinese Version of the Cohen-Mansfield Agitation Inventory-Short Form in Assessing Agitated Behavior.

BACKGROUND: Patients with dementia often present agitated behaviors. The Cohen-Mansfield Agitation Inventory-short form (CMAI-SF) is one of the most widely used instruments to evaluate agitated behaviors that affect patients' quality of life and impose burden on caregivers. However, there is no simplified Chinese version of the CMAI-SF (C-CMAI-SF) in clinical settings. PURPOSE: This study aimed to develop a Chinese version of the C-CMAI-SF and examine its validity and reliability. METHODS: This cross-sectional study included three phases. In Phase I, the original CMAI-SF was translated to Chinese. In Phase II, experts were invited to examine the content validity index (CVI). Phase III was conducted to test the validity and reliability of the C-CMAI-SF. RESULTS: The scale showed good validity and reliability with a scale-level CVI of 0.89, Cronbach's alpha (measure of internal consistency) of 0.874, and test-retest correlation coefficient of 0.902 (for 257 individuals). Using factor analysis, three factors were identified. Regarding concurrent validity, the C-CMAI-SF score was correlated with the Neuropsychiatric Inventory (agitation aggression subscale) and the Cornell Scale for Depression in Dementia (agitation subscale). CONCLUSIONS: The study demonstrated that the C-CMAI-SF is a valid and reliable instrument for evaluating agitated behaviors in people with dementia. RELEVANCE TO CLINICAL PRACTICE: The C-CMAI-SF is an easy and quick tool used to identify and evaluate agitated behaviors in busy clinical settings.

Comparison of long-term effects of exergaming (Xbox one kinet) and companionship programs on attitude towards dementia and the older adults among adolescents: a quasi-experimental longitudinal study.

BACKGROUND: Many studies have been performed on the use of intergenerational programs to improve the negative attitudes and misunderstandings of adolescents toward older people with dementia. However, the findings of these studies are inconclusive. The aim of this study was to compare the long-term effects of exergaming (Kinect) and companionship programs on attitudes toward dementia and the elderly among adolescents. METHODS: A quasi-experimental longitudinal design was used. A total of 200 adolescents aged 12-18 years old were recruited from nine schools in northern Taiwan. The adolescents were assigned to five different groups, namely, a 5-week exergaming group, a 5-week companion group, an 8-week exergaming group, an 8-week companion group, and a control group, using a single blinding procedure. Data collection was performed pretest, post-test and at 1, 3 and 6 months after the post-test. The long-term effects of the two programs (i.e., exergaming and companionship) were analyzed using a generalized estimating equation. RESULTS: Regarding attitudes toward dementia, the 8-week exergaming group had a significantly better attitude than the control group at the 6-month follow-up (p < 0.001). Similarly, the results of the 8-week companion group also showed a significantly improved attitude compared with the control group at the 6-month follow-up (p = 0.041). Regarding attitudes toward the elderly, the 8-week exergaming group had a significantly better attitude than the control group at the 6-month follow-up (p < 0.001). The 8-week companion group had a similar effect on better attitude compared with the control group at the 6-month follow-up (p = 0.016). Furthermore, the 5-week companion group showed a significant improvement compared with the control group at the 6-month follow-up (p = 0.004). CONCLUSIONS: Spending companionship time with older adults is beneficial for improving the attitudes of adolescents toward the elderly. Furthermore, exergaming improves the attitudes of adolescents toward both dementia and older adults. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100053003 . Retrospectively registered on 07/11/2021.

Prenatal Diagnosis of Fetal Congenital Mesoblastic Nephroma and Neonatal Follow-up.

We describe a case of fetal congenital mesoblastic nephroma (CMN) who was diagnosed with ultrasound at 32 weeks of gestation; after delivery, the neonate received left radical nephrectomy, and pathology report confirmed the diagnosis. All cross-sectional imaging studies, such as ultrasonography, computed tomography (CT) scanning, and magnetic resonance imaging, may help to define the organ of origin and the relationship to the ipsilateral kidney. To our knowledge, this is the first case of fetal CMN who was diagnosed in the third trimester and then with a live-born baby in Taiwan. The prenatal examination such as three-dimensional ultrasound and CT image was performed to help us for prenatal diagnosis.

Factors influencing the self-perceived competencies in spiritual care of nurses in the long-term care facilities.

AIMS: To identify key factors influencing institutional nurses' self-perceived competencies in spiritual care. BACKGROUND: In the past decade, interest in spiritual care has been increasing; however, in long-term care facilities, limited knowledge is available about nurses' competencies in spiritual care. METHODS: The cross-sectional study was conducted with 202 nurses in 11 long-term care facilities. Data were collected in a survey using the Spirituality and Spiritual Care Rating Scale, the Nurse Spiritual Care Therapeutics Scale, the Spiritual Care Competence Scale and demographic questions. Data were analysed using stepwise linear regression. RESULTS: Study findings revealed that nurses' perceptions of spirituality and spiritual care, frequency of spiritual care provision and self-satisfaction with the spiritual care given all significantly predicted overall spiritual care competence, which together explain 58% of the total variance. CONCLUSIONS: Improving nurses' perceptions of spirituality and spiritual care and encouraging the performance of spiritual care may be an effective pathway to enhance the spiritual care competence of institutional nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Additional continuing education on spiritual care topics and the establishment of clear guidance and support from institutional administrators are required to enable nurses to deal with spiritual issues as they arise and improve the quality of holistic care.