Efficacy of journaling in the management of mental illness: a systematic review and meta-analysis.

OBJECTIVES: Journaling is a common non-pharmacological tool in the management of mental illness, however, no clear evidence-based guideline exists informing primary care providers on its use. We seek here to present this synthesis that may begin to inform future research and eventual evidence-based guideline development. DESIGN: Of the 3797 articles retrieved from MEDLINE, EMBASE, PsycINFO, 20 peer-reviewed randomised control trials (31 outcomes) met inclusion criteria. These studies addressed the impact of a journaling intervention on PTSD, other anxiety disorders, depression or a combination of the aforementioned. ELIGIBILITY CRITERIA: Peer reviewed, randomised control trials on the impact of journaling on mental illness were included. INFORMATION SOURCES: MEDLINE, EMBASE and PsycINFO. RESULTS: The data are highly heterogeneous (control arm=I2 of 71.2%, intervention arm=I2 of 83.8%) combined with a B-level Strength of Recommendation Taxonomy recommendation. It was additionally found that there is a significant pre-post psychometric scale difference between control (-0.01, 95% CI -0.03 to 0.00) and intervention arms (-0.06, 95% CI -0.09 to -0.03). This 5% difference between groups indicates that a journaling intervention resulted in a greater reduction in scores on patient health measures. Cohen's d effect size analysis of studies suggests a small to moderate benefit. CONCLUSION: Further studies are needed to better define the outcomes. Our review suggests that while there is some randomised control data to support the benefit of journaling, high degrees of heterogeneity and methodological flaws limit our ability to definitively draw conclusions about the benefit and effect size of journaling in a wide array of mental illnesses. Given the low risk of adverse effects, low resource requirement and emphasis on self-efficacy, primary care providers should consider this as an adjunct therapy to complement current evidence-based management.

Management of Lateral Epicondylitis Using Transdermal Nitroglycerin: A Systematic Review.

Lateral epicondylitis (LE), also known as tennis elbow, is an overuse tendinopathy originating from the forearm extensor tendons of the elbow. An emerging therapy for the treatment of LE is the use of transdermal nitroglycerin (NTG) patches for pain relief and improved function. The aim of this systematic review was to assess the current literature on the effect of a transdermal NTG patch for the treatment of LE. A literature search using MEDLINE, EMBASE, SportDiscus, and the Cochrane Database of Systematic Reviews was conducted. Studies selected for inclusion were those in which patients were clinically diagnosed with LE, RCTs, observational studies, and only articles published in English. Studies were excluded if they involved patients <18 years of age or involved patients with a potential alternative source of elbow pain such as previous surgery to the elbow, a previous history of dislocation, fracture of the elbow or tendon rupture, or a referred pain source such as cervical radiculopathy or peripheral nerve involvement. Studies were also excluded if they involved patients who were already prescribed topical NTG for any other indication (i.e., angina), and if the studies had no measurement of symptom relief or measurement or functional scoring. The initial search strategy yielded 69 articles, out of which four met the eligibility criteria and were included in this systematic review. The studies showed improvement in elbow pain in the short-term and mid-term (up to six months), while one study that followed participants for a five-year duration post-treatment, showed no benefit. Three studies used an effective NTG dose of 1.25mg/24h and one study used an effective dose of 1.44mg/24h. Topical NTG was more effective when combined with a tendon rehabilitation program. The most commonly reported side effects of topical NTG were headaches and dermatitis. Overall, the current literature demonstrates that the use of NTG patches for LE improves short- and mid-term pain as well as elbow function. However, more studies are required to fully understand the effect of topical NTG on LE, particularly the effective dose range and the long-term benefits.

Interventions to Improve Medication Adherence in Ethnically Diverse Patients: A Narrative Systematic Review.

INTRODUCTION: Ethnically diverse patients often have lower medication adherence relative to Whites. Certain ethnic groups are also more susceptible to cardiovascular and related diseases. It is critical to develop culturally tailored interventions to improve medication adherence in these ethnically diverse patients. Thus, the aim of this systematic review was to identify what interventions have been developed and tested to improve medication adherence in ethnically diverse patients with cardiovascular-related diseases. METHOD: A systematic search of peer-reviewed literature (MEDLINE, Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Cochrane Central Register of Controlled Trials) was conducted to identify relevant articles. The narrative synthesis was performed based on elements offered by Popay et al. The mixed methods appraisal tool was used to appraise the quality of the included studies. RESULTS: A total of 11,294 records were retrieved, and 34 articles met the inclusion criteria for this systematic review. Synthesis of the literature revealed four overarching intervention strategies used to improve medication adherence: pharmacist-mediated, primarily nurse-led, community-based and community-health worker led, and text-message and phone-based. DISCUSSION: Several approaches can be used to improve medication adherence in ethnically diverse patients, although details on the approaches and conditions to produce optimal improvements for particular ethnic groups need to be determined in future studies. How does this affect culturally congruent health care?

Development of a Culturally Tailored Motivational Interviewing-Based Intervention to Improve Medication Adherence in South Asian Patients.

BACKGROUND: South Asians (SAs) are among the fastest growing ethnic population in Western countries and have a higher risk of cardiovascular diseases relative to the general population. SAs living in Canada also have poorer adherence to medical regimens for treating cardiovascular disease, relative to other ethnic groups. Motivational interviewing (MI) maybe effective in improving health-related behaviour change in patients; however, the research is nascent on the effectiveness of MI in SAs and may also require cultural adaptation. AIM: To develop a culturally tailored MI-based intervention to improve medication adherence in hypertensive SA patients living in Canada. METHODS: Previous literature about medication adherence in SAs was reviewed, along with transcripts and responses to open-ended survey questions from our previous studies with SAs, to draft an MI intervention manual. The manual received extensive feedback from the study team, SA community members and health-care providers who work with SA patients. The feedback was used to refine the manual and make it culturally tailored and relevant to SA hypertensive patients living in Canada. RESULTS: A culturally tailored MI-based manual which we called a "motivational communication manual" was developed to support a study focused on improving medication adherence in SA hypertensive patients. The development process, components (eg, being culturally sensitive, family involvement, providing education about medications, reminders, etc.) and cultural nuances included in the manual are described in this paper. CONCLUSION: This is the first culturally tailored MI-based intervention manual that has been developed with the aim of improving medication adherence in hypertensive SA patients and that includes direct feedback from SA community members. Use of this manual may improve the accessibility and adoption of MI-based practices in improving health behaviours in SAs living in Canada as well as encourage further research studies and clinical trials with SA patients.

South Asian patients' perceptions and experiences of compassion in healthcare.

Background: South Asians are one of the fastest growing ethnic populations in Western countries. Accordingly, providing culturally sensitive healthcare to South Asians is becoming increasingly important. Compassion is a key component of quality healthcare and is central to bridging ethnic and cultural differences between patients and their healthcare providers (HCP).Objective: We aimed to identify and describe the perspectives, experiences, importance, and impact of compassion among South Asian patients.Methods: Straussian grounded theory was used to examine the perspectives of South Asians patients who had recent experience(s) with the Canadian healthcare system. A convenience sample of 19 South Asian participants underwent semi-structured audio-recorded interviews in either English, Hindi, or Punjabi. Transcribed interview data were analyzed using constant comparison.Results: Three categories were generated from the data: (1) South Asians' understandings of compassion, (2) HCPs' cultural sensitivity as an indicator of compassion, and (3) enhancing compassion: importance and patient recommendations for overcoming barriers to compassion. The first category included themes exploring South Asian patients' perspectives of compassion. The second category was divided into themes which examined how delivery and receipt of compassion can be influenced by ethnic and cultural differences between patients and HCPs. The third category consisted of themes highlighting participants' views on the importance of compassion, recommendations for overcoming language and cultural barriers to providing compassion, and the role of compassion in bridging language, culture and ethnic differences between patients and HCPs.Conclusion: Compassion was described as a universal concept that is interpreted through the cultural and ethnic background of the recipient and provider in the way it is perceived, enacted, and received. This information can aid HCP to modulate compassion to South Asian patients and may provide a foundation for future studies on compassion within other cultural groups.

Motivational Interviewing in Ethnic Populations.

Motivational interviewing (MI) is an effective means of facilitating behavior change in a variety of health conditions. However, given its origins in western psychology, its utility in ethnic populations is unclear. Our objective was to examine the effectiveness of MI and its components in people of varying ethnicities and how they may experience MI. We undertook a narrative systematic review of the literature, searching only peer-reviewed research up until February, 2019 with participants who were: ≥ 18 years of age, belonging to an ethnic origin relevant to Canada's population, and had a health related concern (e.g. drug and alcohol addictions, chronic illness). Four thousand seven hundred and sixty-one citations were retrieved, and ultimately 61 met the inclusion criteria. Cultural acknowledgment and considerations with MI, when described, enhanced effectiveness of MI in most ethnic groups. The length and the number of sessions had no apparent influence on the success of MI. When examined, most study participants reported acceptance of the intervention; however, there were challenges, most notably for Chinese patients. MI can be effective in a variety of ethnic groups, particularly when cultural acknowledgement is included in the process.

Motivational Interviewing and Self-care Practices in Adult Patients With Heart Failure: A Systematic Review and Narrative Synthesis.

BACKGROUND: Heart failure contributes to frequent hospitalizations, large healthcare costs, and high mortality. Heart failure management includes patient adherence to strict self-care practices (ie, symptom recognition, limiting sodium and fluids, monitoring weight, maintaining an active lifestyle, and medication adherence as well as monitoring other medical conditions). These practices can be difficult to enact and maintain. Motivational interviewing, although not studied extensively in patients with heart failure, may enhance patients' abilities to enact and maintain self-care practices. OBJECTIVE: The aim of this study was to examine the effectiveness of motivational interviewing on self-care practices in the adult population with heart failure. METHODS: We conducted a narrative systematic review of peer-reviewed research literature focused on motivational interviewing in adult patients with heart failure. The following databases were searched from database inception to March 2019: MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, ERIC, Educational Resource Complete, and Scopus. Of 1158 citations retrieved, 7 studies met the inclusion criteria. RESULTS: Outcomes were focused on self-care adherence (ie, maintenance, management, confidence), physical activity/exercise, and knowledge of self-care. Motivational interviewing has been effectively used either alone or in combination with other therapies and has been used in-home, over the telephone, and in hospital/clinic settings, although face-to-face interventions seem to be more effective. A number of limitations were noted in the included studies. CONCLUSION: Motivational interviewing is a potentially effective adjunct to enhance self-care practices in patients with heart failure. Further high-quality research is needed to support changes in clinical practice.

The impact of ethnic/racial status on access to care and outcomes after stroke: A narrative systematic review.

Improving poststroke outcomes is contingent on early symptom recognition and timely access to life-saving interventions. Several studies have reported differences in access to care among stroke patients from different ethnic/racial backgrounds, although some of the findings present contrasting results. A 2011 AHA/ASA Scientific Statement noted ethnic/racial disparities in access and receipt of stroke care. The aim of this systematic review was to comprehensively identify and describe the impact of ethnic/racial status on access to care after onset of stroke symptoms. We undertook a systematic search of the following databases: Cochrane, JBI, Trove, ProQuest, Ethos, CINAHL, MEDLINE, Embase, PsycINFO, Academic Search Elite, and Scopus to find relevant qualitative, quantitative, or mixed-method studies focused on ethnicity/race, stroke, and access to health care services in adult (≥18 years) stroke patients. A narrative synthesis approach was used to generate key themes describing the impact of ethnic/racial differences in stroke-related care. Twenty-five studies were included in this systematic review. Narrative synthesis yielded 4 key themes related to differences in 1) transportation to hospital, emergency wait time, hospital admission, and length of stay; 2) receipt of intravenous thrombolysis; 3) receipt of mechanical-reperfusion therapies and imaging procedures; and 4) risk of death, based on ethnicity/race. Generally, but not universally, ethnic/racial minorities (particularly black patients) had lower access to poststroke care, but no greater mortality risk. Reducing health-related disparities will improve treatment outcomes among ethnic stroke patients.

mRNA levels are buffered upon knockdown of RNA decay and translation factors via adjustment of transcription rates in human HepG2 cells.

Evidence from yeast and mammals argues the existence of cross-talk between transcription and mRNA decay. Stabilization of transcripts upon depletion of mRNA decay factors generally leads to no changes in mRNA abundance, attributing this to decreased transcription rates. We show that knockdown of human XRN1, CNOT6 and ETF1 genes in HepG2 cells led to significant alteration in stability of specific mRNAs, alterations in half-life were inversely associated with transcription rates, mostly not resulting in changes in abundance. We demonstrate the existence of the gene expression buffering mechanism in human cells that responds to both transcript stabilization and destabilization to maintain mRNA abundance via altered transcription rates and may involve translation. We propose that this buffering may hold novel cancer therapeutic targets.

Assessing the credibility and transferability of the patient compassion model in non-cancer palliative populations.

BACKGROUND: A lack of evidence and psychometrically sound measures of compassion necessitated the development of the first known, empirically derived, theoretical Patient Compassion Model (PCM) generated from qualitative interviews with advanced cancer inpatients. We aimed to assess the credibility and transferability of the PCM across diverse palliative populations and settings. METHODS: Semi-structured, audio-recorded qualitative interviews were conducted with 20 patients with life-limiting diagnoses, recruited from 4 settings (acute care, homecare, residential care, and hospice). Participants were first asked to share their understandings and experiences of compassion. They were then presented with an overview of the PCM and asked to determine whether: 1) the model resonated with their understanding and experiences of compassion; 2) the model required any modification(s); 3) they had further insights on the model's domains and/or themes. Members of the research team analyzed the qualitative data using constant comparative analysis. RESULTS: Both patients' personal perspectives of compassion prior to viewing the model and their specific feedback after being provided an overview of the model confirmed the credibility and transferability of the PCM. While new codes were incorporated into the original coding schema, no new domains or themes emerged from this study sample. These additional codes provided a more comprehensive understanding of the nuances within the domains and themes of the PCM that will aid in the generation of items for an ongoing study to develop a patient reported measure of compassion. CONCLUSIONS: A diverse palliative patient population confirmed the credibility and transferability of the PCM within palliative care, extending the rigour and applicability of the PCM that was originally developed within an advanced cancer population. The views of a diverse palliative patient population on compassion helped to validate previous codes and supplement the existing coding schema, informing the development of a guiding framework for the generation of a patient-reported measure of compassion.

The colours and contours of compassion: A systematic review of the perspectives of compassion among ethnically diverse patients and healthcare providers.

OBJECTIVE: To identify and describe the perspectives, experiences, importance, and impact of compassionate care among ethnically diverse population groups. METHODS: A systematic search of peer-reviewed research focused on compassionate care in ethnically diverse populations published between 1946 and 2017 was conducted. RESULTS: A total of 2296 abstracts were retrieved, out of which 23 articles met the inclusion criteria. Synthesis of the literature identified the perspectives, facilitators and barriers of compassion in healthcare within ethnic groups. Compassion was described as being comprised of healthcare provider (HCP) virtues (honesty, kindness, helpful, non-judgment) and actions (smile, touch, care, support, flexibility) aimed at relieving the suffering of patients. The importance and impact of providing compassion to ethnically diverse patients was also identified which included overcoming cultural differences, alleviating distress at end-of-life, promoting patient dignity and improving patient care. This review also identified the need for more contextual studies directly exploring the topic of compassion from the perspectives of individuals within diverse ethnic groups, rather than superimposing a pre-defined, enculturated and researcher-based definition of compassion. CONCLUSIONS: This review synthesizes the current evidence related to perceptions of compassion in healthcare among diverse ethnic groups and the role that compassion can play in bridging ethno-cultural differences and associated challenges, along with identifying gaps in literature related to compassionate care within diverse ethnic groups. Establishing an evidence base grounded in the direct accounts of members of diverse ethnic communities can enhance culturally sensitive compassionate care and improve compassion related health outcomes among diverse ethnic groups.

Healthcare providers' perspectives on perceived barriers and facilitators of compassion: Results from a grounded theory study.

AIMS AND OBJECTIVES: To explore healthcare provider perspectives and experiences of perceived barriers and facilitators of compassion. BACKGROUND: Compassion is considered a component of quality health care that healthcare providers are increasingly expected to provide. While there have been some studies exploring facets of healthcare providers' perspectives on the barriers and facilitators to providing compassion, a comprehensive understanding based on direct reports from healthcare providers is lacking. DESIGN: Data were collected via focus groups and semi-structured interviews. Data was analyzed in accordance with Straussian grounded theory. METHODS: Semistructured focus groups with frontline healthcare providers and individual interviews with peer-nominated exemplary compassionate care providers were audio-recorded, professionally transcribed and analysed. Fifty-seven participants were recruited from three healthcare settings within both rural and urban settings in Alberta, Canada, using convenience, snowball and theoretical sampling. RESULTS: Qualitative analysis of the data generated two categories and associated themes and subthemes delineating perceived barriers and facilitators to compassion. The first category, challenges to compassion, reflects participants' discomfort associating the notion of barriers to compassion and contained several themes participants conceptualised as challenges: personal challenges, relational challenges, systemic challenges and maladaptive responses. The second category, facilitators of compassion, included the themes of personal facilitators, relational facilitators, systemic facilitators and adaptive responses of intentional action. CONCLUSION: Although participants described certain factors such as system and time constraints along with interaction styles of patients and families that can challenge healthcare provider compassion, these challenges were not considered insurmountable. While acknowledging these as challenges, participants identified healthcare providers themselves, including their responses towards the identified challenges of compassion, as significant factors in this process-a novel finding from this study. This study provides insight into healthcare providers' perspectives on the notion of barriers and facilitators in the provision of compassion. RELEVANCE TO CLINICAL PRACTICE: This study provides a blueprint for optimising compassion on a personal, relational and system level.

What are healthcare providers' understandings and experiences of compassion? The healthcare compassion model: a grounded theory study of healthcare providers in Canada.

BACKGROUND: Healthcare providers are considered the primary conduit of compassion in healthcare. Although most healthcare providers desire to provide compassion, and patients and families expect to receive it, an evidence-based understanding of the construct and its associated dimensions from the perspective of healthcare providers is needed. OBJECTIVES: The aim of this study was to investigate healthcare providers' perspectives and experiences of compassion in order to generate an empirically derived, clinically informed model. DESIGN: Data were collected via focus groups with frontline healthcare providers and interviews with peer-nominated exemplary compassionate healthcare providers. Data were independently and collectively analysed by the research team in accordance with Straussian grounded theory. SETTING AND PARTICIPANTS: 57 healthcare providers were recruited from urban and rural palliative care services spanning hospice, home care, hospital-based consult teams, and a dedicated inpatient unit within Alberta, Canada. RESULTS: Five categories and 13 associated themes were identified, illustrated in the Healthcare Provider Compassion Model depicting the dimensions of compassion and their relationship to one another. Compassion was conceptualised as-a virtuous and intentional response to know a person, to discern their needs and ameliorate their suffering through relational understanding and action. CONCLUSIONS: An empirical foundation of healthcare providers' perspectives on providing compassionate care was generated. While the dimensions of the Healthcare Provider Compassion Model were congruent with the previously developed Patient Model, further insight into compassion is now evident. The Healthcare Provider Compassion Model provides a model to guide clinical practice and research focused on developing interventions, measures and resources to improve it.

Retention of Ethnic Participants in Longitudinal Studies.

We aimed to identify effective participant retention strategies utilized in longitudinal studies of ethnic groups, specifically those from South Asian and Chinese communities. We conducted a systematic review of the literature focusing on the retention of ethnic minorities in longitudinal studies, up until April 2017. Only peer-reviewed research was included. 11,316 citations were retrieved, of which 4808 were duplicates and 51 met the inclusion criteria. Financial incentives, involving key community members, flexible scheduling, developing trust and personal connections with participants, and having extensive participant contact information are key facilitators. We also describe our extensive experience of retaining South Asian and Chinese participants in longitudinal studies. Key retention strategies for these groups include involving family members, informing participants about potential personal and community benefits, being flexible in how and when the interviews are conducted, and providing multiple language options. There is little published evidence or direction regarding how to retain study participants from South Asian or Chinese communities. However, there can be some learning from studies focused on other ethnic groups. Establishing an evidence-based approach, including facilitators and barriers to retention of these groups in longitudinal studies would help to determine study feasibility, validity, and ultimately to reduce health disparities among South Asian or Chinese communities.

Ethno-cultural Preferences in Receipt of Heart Health Information.

OBJECTIVE: We attempted to understand how people of South Asian and Chinese descent prefer to receive health information. METHODS: To achieve this end we conducted a search of academic and grey literature articles published between 1946 and 2016. To be included, articles had to be focused South Asian and Chinese specific ethno-culturally-based preferences of receiving health information. RESULTS: A total of 3478 abstracts were retrieved, of which, 27 articles met the inclusion criteria. We were able to identify South Asian and Chinese people's preferences for and facilitators of receiving health information. South Asians and Chinese preferred health information and programs that were more culturally relevant and appealing, had translations into South Asian and Chinese languages, and used simple terms as opposed to technical jargon. CONCLUSIONS: There is little direction regarding for how to tai- lor health information South Asian and Chinese ethno-cultural groups. Having evidence-based information about how South Asians and Chinese prefer to receive health information has potential to enhance patients' learning and health literacy, improve clinical outcomes, and reduce health disparities.

Can Self-Compassion Promote Healthcare Provider Well-Being and Compassionate Care to Others? Results of a Systematic Review.

BACKGROUND: This meta-narrative review, conducted according to the RAMESES (Realist And Meta-narrative Evidence Syntheses: Evolving Standards) standards, critically examines the construct of self-compassion to determine if it is an accurate target variable to mitigate work-related stress and promote compassionate caregiving in healthcare providers. METHODS: PubMed, Medline, CINAHL, PsycINFO, and Web of Science databases were searched. Studies were coded as referring to: (1) conceptualisation of self-compassion; (2) measures of self-compassion; (3) self-compassion and affect; and (4) self-compassion interventions. A narrative approach was used to evaluate self-compassion as a paradigm. RESULTS: Sixty-nine studies were included. The construct of self-compassion in healthcare has significant limitations. Self-compassion has been related to the definition of compassion, but includes limited facets of compassion and adds elements of uncompassionate behavior. Empirical studies use the Self-Compassion Scale, which is criticised for its psychometric and theoretical validity. Therapeutic interventions purported to cultivate self-compassion may have a broader effect on general affective states. An alleged outcome of self-compassion is compassionate care; however, we found no studies that included patient reports on this primary outcome. CONCLUSION: We critically examine and delineate self-compassion in healthcare providers as a composite of common facets of self-care, healthy self-attitude, and self-awareness rather than a construct in and of itself.

Atrogin-1 Increases Smooth Muscle Contractility Through Myocardin Degradation.

Atrogin-1, an E3 ligase present in skeletal, cardiac and smooth muscle, down-regulates myocardin protein during skeletal muscle differentiation. Myocardin, the master regulator of smooth muscle cell (SMC) differentiation, induces expression of smooth muscle marker genes through its association with serum response factor (SRF), which binds to the CArG box in the promoter. Myocardin undergoes ubiquitylation and proteasomal degradation. Evidence suggests that proteasomal degradation of myocardin is critical for myocardin to exert its transcriptional activity, but there is no report about the E3 ligase responsible for myocardin ubiquitylation and subsequent transactivation. Here, we showed that overexpression of atrogin-1 increased contractility of cultured SMCs and mouse aortic tissues in organ culture. Overexpression of dominant-negative myocardin attenuated the increase in SMC contractility induced by atrogin-1. Atrogin-1 overexpression increased expression of the SM contractile markers while downregulated expression of myocardin protein but not mRNA. Atrogin-1 also ubiquitylated myocardin for proteasomal degradation in vascular SMCs. Deletion studies showed that atrogin-1 directly interacted with myocardin through its amino acids 284-345. Immunostaining studies showed nuclear localization of atrogin-1, myocardin, and the Rpt6 subunit of the 26S proteasome. Atrogin-1 overexpression not only resulted in degradation of myocardin but also increased recruitment of RNA Polymerase II onto the promoters of myocardin target genes. In summary, our results have revealed the roles for atrogin-1 in the regulation of smooth muscle contractility through enhancement of myocardin ubiquitylation/degradation and its transcriptional activity. J. Cell. Physiol. 232: 806-817, 2017. © 2016 Wiley Periodicals, Inc.

Potential Role of Glycogen Synthase Kinase-3ß in Regulation of Myocardin Activity in Human Vascular Smooth Muscle Cells.

Glycogen synthase kinase (GSK)-3ß, a serine/threonine kinase with an inhibitory role in glycogen synthesis in hepatocytes and skeletal muscle, is also expressed in cardiac and smooth muscles. Inhibition of GSK-3ß results in cardiac hypertrophy through reducing phosphorylation and increasing transcriptional activity of myocardin, a transcriptional co-activator for serum response factor. Myocardin plays critical roles in differentiation of smooth muscle cells (SMCs). This study, therefore, aimed to examine whether and how inhibition of GSK-3ß regulates myocardin activity in human vascular SMCs. Treatment of SMCs with the GSK-3ß inhibitors AR-A014418 and TWS 119 significantly reduced endogenous myocardin activity, as indicated by lower expression of myocardin target genes (and gene products), CNN1 (calponin), TAGLN1 (SM22), and ACTA2 (SM α-actin). In human SMCs overexpressing myocardin through the T-REx system, treatment with either GSK-3ß inhibitor also inhibited the expression of CNN1, TAGLN1, and ACTA2. These effects of GSK-3ß inhibitors were mimicked by transfection with GSK-3ß siRNA. Notably, both AR-A014418 and TWS 119 decreased the serine/threonine phosphorylation of myocardin. The chromatin immunoprecipitation assay showed that AR-A014418 treatment reduced myocardin occupancy of the promoter of the myocardin target gene ACTA2. Overexpression of a dominant-negative GSK-3ß mutant in myocardin-overexpressing SMCs reduced the expression of calponin, SM22, and SM α-actin. As expected, overexpression of constitutively active or wild-type GSK-3ß in SMCs without myocardin overexpression increased expression of these proteins. In summary, our results indicate that inhibition of GSK-3ß reduces myocardin transcriptional activity, suggesting a role for GSK-3ß in myocardin transcriptional activity and smooth muscle differentiation.

Dual regulation of myocardin expression by tumor necrosis factor-α in vascular smooth muscle cells.

De-differentiation of vascular smooth muscle cells (VSMCs) plays a critical role in the development of atherosclerosis, a chronic inflammatory disease involving various cytokines such as tumor necrosis factor-α (TNFα). Myocardin is a co-factor of serum response factor (SRF) and is considered to be the master regulator of VSMC differentiation. It binds to SRF and regulates the expression of contractile proteins in VSMCs. Myocardin is also known to inhibit VSMC proliferation by inhibiting the NF-κB pathway, whereas TNFα is known to activate the NF-κB pathway in VSMCs. NF-κB activation has also been shown to inhibit myocardin expression and smooth muscle contractile marker genes. However, it is not definitively known whether TNFα regulates the expression and activity of myocardin in VSMCs. The current study aimed to investigate the role of TNFα in regulating myocardin and VSMC function. Our studies showed that TNFα down-regulated myocardin expression and activity in cultured VSMCs by activating the NF-κB pathway, resulting in decreased VSMC contractility and increased VSMC proliferation. Surprisingly, we also found that TNFα prevented myocardin mRNA degradation, and resulted in a further significant increase in myocardin expression and activity in differentiated VSMCs. Both the NF-κB and p44/42 MAPK pathways were involved in TNFα regulation of myocardin, which further increased the contractility of VSMCs. These differential effects of TNFα on myocardin seemingly depended on whether VSMCs were in a differentiated or de-differentiated state. Taken together, our results demonstrate that TNFα differentially regulates myocardin expression and activity, which may play a key role in regulating VSMC functions.

Dietary intake of Curcuma longa and Emblica officinalis increases life span in Drosophila melanogaster.

Intake of food and nutrition plays a major role in affecting aging process and longevity. However, the precise mechanisms underlying the ageing process are still unclear. To this respect, diet has been considered to be a determinant of ageing process. In order to better illustrate this, we used Drosophila melanogaster as a model and fed them orally with different concentrations of two commonly used Indian medicinal plant products, Curcuma longa (rhizome) and Emblica officinalis (fruit). The results revealed significant increase in life span of Drosophila flies on exposure to both the plant products, more efficiently by C. Longa than by E. officinalis. In order to understand whether the increase in lifespan was due to high-antioxidant properties of these medicinal plants, we performed enzymatic assays to assess the SOD and catalase activities in case of both treated and control Drosophila flies. Interestingly, the results support the free radical theory of aging as both these plant derivatives show high reactive oxygen species (ROS) scavenging activities.