A multiple technology-based and individually-tailored Sit Less program for people with cardiovascular disease: A randomized controlled trial study protocol.

Sedentary behavior, a key modifiable risk factor for cardiovascular disease, is prevalent among cardiovascular disease patients. However, few interventions target sedentary behavior in this group. This paper describes the protocol of a parallel two-group randomized controlled trial for a novel multi-technology sedentary behavior reduction intervention for cardiovascular disease patients (registered at Clinicaltrial.gov, NCT05534256). The pilot trial (n = 70) will test a 12-week "Sit Less" program, based on Habit Formation theory. The 35 participants in the intervention group will receive an instructional goal-setting session, a Fitbit for movement prompts, a smart water bottle (HidrateSpark) to promote hydration and encourage restroom breaks, and weekly personalized text messages. A control group of 35 will receive the American Heart Association's "Answers by Heart" fact sheets. This trial will assess the feasibility and acceptability of implementing the "Sit Less" program with cardiovascular disease patients and the program's primary efficacy in changing sedentary behavior, measured by the activPAL activity tracker. Secondary outcomes include physical activity levels, cardiometabolic biomarkers, and patient-centered outcomes (i.e. sedentary behavior self-efficacy, habit strength, and fear of movement). This study leverages commonly used mobile and wearable technologies to address sedentary behavior in cardiovascular disease patients, a high-risk group. Its findings on the feasibility, acceptability and primary efficacy of the intervention hold promise for broad dissemination.

Twenty-Four-Hour Ambulatory Blood Pressure Monitoring Parameters During Pregnancy: A Pilot Study.

Introduction: Maternal blood pressure (BP) is a critical cardiovascular marker with profound implications for maternal and fetal well-being, particularly in the detection of hypertensive disorders during pregnancy. Although conventional clinic-based BP (CBP) measurements have traditionvally been used, monitoring 24-hour ambulatory BP (ABP) has emerged as a more reliable method for assessing BP levels and diagnosing conditions such as gestational hypertension and preeclampsia/eclampsia. This study aimed to assess the feasibility and acceptability of 24-hour ABP monitoring in pregnant women and report on various ABP parameters, including ambulatory blood pressure variability (ABPV). Method: A prospective cross-sectional study design was employed, involving 55 multipara pregnant women with and without prior adverse pregnancy outcomes (APOs). The participants underwent baseline assessments, including anthropometrics, resting CBP measurements, and the placement of ABP and actigraphy devices. Following a 24-hour period with these devices, participants shared their experiences to gauge device acceptability. Pregnancy outcomes were collected postpartum. Results: Twenty-four-hour ABP monitoring before 20 weeks of gestation is feasible for women with and without prior APOs. Although some inconvenience was noted, the majority of participants wore the ABP monitoring device for the entire 24-hour period. Pregnant women who later experienced APOs exhibited higher 24-hour ABP and ABPV values in the early stages of pregnancy. Conclusion: The study highlights the potential benefits of 24-hour ABP monitoring as a valuable tool in prenatal care, emphasizing the need for further research in this area.

Characterization of sleep efficiency transitions in family caregivers.

Family caregivers are at high risk of psychological distress and low sleep efficiency resulting from their caregiving responsibilities. Although psychological symptoms are associated with sleep efficiency, there is limited knowledge about the association of psychological distress with variations in sleep efficiency. We aimed to characterize the short- and long-term patterns of caregivers' sleep efficiency using Markov chain models and compare these patterns between groups with high and low psychological symptoms (i.e., depression, anxiety, and caregiving stress). Based on 7-day actigraphy data from 33 caregivers, we categorized sleep efficiency into three states, < 75% (S1), 75-84% (S2), and ≥ 85% (S3), and developed Markov chain models. Caregivers were likely to maintain a consistent sleep efficiency state from one night to the next without returning efficiently to a normal state. On average, it took 3.6-5.1 days to return to a night of normal sleep efficiency (S3) from lower states, and the long-term probability of achieving normal sleep was 42%. We observed lower probabilities of transitioning to or remaining in a normal sleep efficiency state (S3) in the high depression and anxiety groups compared to the low symptom groups. The differences in the time required to return to a normal state were inconsistent by symptom levels. The long-term probability of achieving normal sleep efficiency was significantly lower for caregivers with high depression and anxiety compared to the low symptom groups. Caregivers' sleep efficiency appears to remain relatively consistent over time and does not show rapid recovery. Caregivers with higher levels of depression and anxiety may be more vulnerable to sustained suboptimal sleep efficiency.

Sleep Deficiency by Caregiving Status: Findings From Nationally Representative Data.

OBJECTIVE: Caregiving demands may influence caregivers' sleep duration and quality, which are essential for optimal health. We aimed to examine the association between caregiving status and sleep deficiency (i.e., short sleep duration and/or poor quality) and identify factors associated with sleep deficiency among caregivers. METHODS: This secondary analysis used data from 3870 adults living in the United States, obtained from the 2019 Health Information National Trends Survey. Multinomial logistic regressions were performed to examine the association between caregiving status (i.e., caregivers vs. non-caregivers) and sleep status (i.e., normal duration-good quality [optimal sleep, reference], short duration-good quality, normal duration-poor quality, and short duration-poor quality), and to identify caregiving-related factors associated with sleep deficiency in the caregiver group. RESULTS: Compared to non-caregivers, caregivers were more likely to report short sleep duration (<7 hours) with good quality sleep (relative risk ratio [RRR] = 1.566, 95% CI [1.238, 1.980]) or poor quality sleep (RRR = 1.376, 95% CI [1.034, 1.832]) than the optimal sleep status. Caregivers providing care for ≥20 hours per week (vs. <20 hours) and providing care to individuals with dementia (vs. no dementia caregiving) were 2.8 times more likely to report normal sleep duration with poor sleep quality than optimal sleep (RRR = 2.796, 95% CI [1.125, 6.950]; RRR = 2.776, 95% CI [1.154, 6.675], respectively). CONCLUSION: The findings of a higher risk of sleep deficiency among caregivers suggest that health care providers need to assess both caregivers' sleep duration and quality status. Interventions tailored to the caregiving context are also warranted.

Examining factors affecting self-care-self-regulation among registered nurses using path analysis.

BACKGROUND: Practicing self-care is a requisite for nurses as they face the extreme physical, mental, and emotional challenges presented by the pandemic era. This study aimed to examine factors that contribute to self-care-self-regulation (SCSR) and investigate the mediation effect of psychological and physical health in the relationship between work stress and SCSR among registered nurses in the United States. MATERIALS AND METHODS: This cross-sectional study was conducted on the data collected from 386 registered nurses who completed an online survey over a 3-week period during the COVID-19 pandemic (April 19 to May 6, 2020). The survey assessed demographic and work-related characteristics, work stress, depressive mood, self-rated health, and SCSR. The model was tested with depressive mood as the first mediator and self-rated health as the second mediator. The potential serial mediation effect was analyzed using PROCESS macros adjusting for covariates. RESULTS: The sequential indirect effect of work stress on SCSR through depressive mood and self-rated health in series was significant, while its direct effect was not. CONCLUSION: The findings of the path analysis demonstrate that psychological and physical health status is important to promote self-care behaviors when nurses experience high work stress.

Pregnancy-associated takotsubo cardiomyopathy hospitalizations in the United States.

Takotsubo cardiomyopathy (TCM) is most common not only in postmenopausal women aged ≥50 yr but also in pregnant individuals. However, there are no national estimates on the prevalence, timing of occurrence, correlates, and outcomes of pregnancy-associated TCM. Using the Nationwide Inpatient Sample (NIS: 2016-2020), we describe rates of pregnancy-associated TCM hospitalizations among 13- to 49-yr-old pregnant individuals in the United States by selected demographic, behavioral, hospital, and clinical characteristics. Joinpoint regression was used to describe the annual average percent change of pregnancy-associated TCM hospitalizations. Survey logistic regression was used to measure the association of pregnancy-associated TCM hospitalizations with maternal outcomes. Of the 19,754,535 pregnancy-associated hospitalizations, 590 were TCM associated. The overall trend in pregnancy-associated TCM hospitalizations remained stable during the study period. The majority of TCM occurred during the postpartum, followed by antepartum and delivery-associated hospitalizations. When compared with pregnancy hospitalizations without TCM, those with TCM were more likely to be over the age of 35 yr and use tobacco and opioids. Comorbidities during TCM-associated pregnancy hospitalizations included heart failure, coronary artery disease, hemorrhagic stroke, and hypertension. After controlling for potential confounders, the odds of pregnancy-associated TCM hospitalizations were 98.7 times [adjusted odds ratio (aOR) = 98.66, 95% confidence interval (CI) 31.23-311.64] and 14.7 times (aOR = 14.75, 95% CI 9.99-21.76) higher for experiencing in-hospital mortality and a prolonged hospital stay, respectively, than those without TCM. Although rare, pregnancy-associated TCM hospitalization is more likely to occur during the postpartum period and is associated with in-hospital mortality and prolonged hospital stay.NEW & NOTEWORTHY Although rare, pregnancy-associated takotsubo cardiomyopathy hospitalizations are more likely to occur during the postpartum period and are associated with in-hospital mortality and prolonged hospital stay.

Association of disrupted sleep with 24-hour blood pressure variability in caregivers.

BACKGROUND: A growing body of research highlights the negative impact of caregiving on cardiovascular disease (CVD) risk. OBJECTIVES: This study aimed to examine associations of psychological symptoms and sleep quality with 24-hour blood pressure variability (BPV), which is an independent predictor of CVD, among family caregivers of community-dwelling individuals with chronic illness. METHODS: For this cross-sectional study, we assessed caregiving burden and depressive symptoms using questionnaires and 7-day sleep quality (i.e., number of awakenings, wake after sleep onset, sleep efficiency) using an actigraph. The participants carried out a 24-hour ambulatory BP monitoring for systolic and diastolic BPV over 24 h and during awake/sleep times. We performed Pearson's correlations and multiple linear regression. RESULTS: The analytic sample consisted of 30 caregivers (25 female; mean age 62 years). The number of awakenings during sleep was positively correlated with systolic BPV-awake (r = 0.426, p = 0.019) and diastolic BPV-awake (r = 0.422, p = 0.020). Sleep efficiency was negatively correlated with diastolic BPV-awake (r = -0.368, p = 0.045). Caregiving burden and depressive symptoms were not correlated with BPV. After controlling for age and mean arterial pressure, the number of awakenings was significantly associated with increased systolic BPV-24 h (ß = 0.194, p = 0.018) and systolic BPV-awake (ß = 0.280, p = 0.002), respectively. CONCLUSIONS: Caregivers' disrupted sleep may play a role in increased CVD risk. While these findings should be confirmed in large clinical studies, improving sleep quality would need to be considered in CVD prevention for caregivers.

Shared decision-making in persons living with dementia: A scoping review.

Evidence supports that older adults with cognitive impairment can reliably communicate their values and choices, even as cognition may decline. Shared decision-making, including the patient, family members, and healthcare providers, is critical to patient-centered care. The aim of this scoping review was to synthesize what is known about shared decision-making in persons living with dementia. A scoping review was completed in PubMed, CINAHL, and Web of Science. Keywords included content areas of dementia and shared decision-making. Inclusion criteria were as follows: description of shared or cooperative decision making, cognitively impaired patient population, adult patient, and original research. Review articles were excluded, as well as those for which the formal healthcare provider was the only team member involved in the decision-making (e.g., physician), and/or the patient sample was not cognitively impaired. Systematically extracted data were organized in a table, compared, and synthesized. The search yielded 263 non-duplicate articles that were screened by title and abstract. Ninety-three articles remained, and the full text was reviewed; 32 articles were eligible for this review. Studies were from across Europe (n = 23), North America (n = 7), and Australia (n = 2). The majority of the articles used a qualitative study design, and 10 used a quantitative study design. Categories of similar shared decision-making topics emerged, including health promotion, end-of-life, advanced care planning, and housing decisions. The majority of articles focused on shared decision-making regarding health promotion for the patient (n = 16). Findings illustrate that shared decision-making requires deliberate effort and is preferred among family members, healthcare providers, and patients with dementia. Future research should include more robust efficacy testing of decision-making tools, incorporation of evidence-based shared decisionmaking approaches based on cognitive status/diagnosis, and consideration of geographical/cultural differences in healthcare delivery systems.

Social withdrawal in Parkinson's disease: A scoping review.

BACKGROUND: Parkinson's disease (PD) can interfere with individuals' social functioning and lead to social withdrawal. Social withdrawal may result in negative outcomes for persons with PD and their caregivers, such as decreased quality of life. It is necessary to understand the nature of social withdrawal in PD in order to develop strategies to address this issue and prevent negative outcomes. OBJECTIVE: The purpose of this scoping review was to synthesize existing evidence regarding social withdrawal in PD. METHODS: We searched PubMed, CINAHL, and PsycINFO for studies of social withdrawal in individuals living with PD. Findings were organized according to study characteristics, measurement and description of social withdrawal, prevalence, associated factors, and interventions. RESULTS: Fifty-eight studies were included. We found that persons with PD reduced social activities voluntarily and involuntarily, and social withdrawal was related to various factors including physical, cognitive, and psychiatric symptoms and perceived stigma. Community-based social activity programs appeared to improve social participation. Few studies employed longitudinal methods or tested interventions to reduce social withdrawal. CONCLUSIONS: Social withdrawal is associated with various negative outcomes in PD, though more research is needed to understand the true scope of this problem. Limitations in social withdrawal research include vague conceptualization and methodological limitations (i.e., instrumentation and study design), as well as a paucity of interventional studies. The findings of this review can be used to guide hypothesis generation and future study design, with the ultimate goal of mitigating social withdrawal and improving quality of life for people with PD.

The impact of COVID-19 trade measures on agricultural and food trade.

This paper assesses the determinants of temporary non-tariff measures (NTMs) in response to COVID-19 and their implications for the agricultural and food trade. Using a control function approach, we show that economic and pandemic considerations played an essential role in implementing such NTMs. Relying on variation between treated and untreated varieties, we estimate a dynamic post-event trade response of 5.4% for import facilitating and -27.5% for export restricting NTMs. After revoking them, their trade effects fade away, implying that these temporary trade policies were effective in achieving the set policy goals, causing only a limited degree of long-term trade disruptions.

Cardiovascular Disease Incidence and Risk in Family Caregivers of Adults With Chronic Conditions: A Systematic Review.

BACKGROUND: Family caregivers experience psychological distress or physical strain that may lead to an increased risk of cardiovascular disease (CVD) morbidity and mortality. OBJECTIVE: This systematic review aimed to describe the current evidence and gaps in the literature on measures used to assess CVD outcomes in family caregivers, the association of caregiving with CVD incidence/risk outcomes, and associated factors in family caregivers of patients with chronic disease. METHODS: Medline, PubMed, CINAHL, Web of Science, and Google Scholar were searched for English-language, peer-reviewed studies published from 2008 to 2020 that examined CVD incidence and risk among family caregivers of adults with chronic conditions. RESULTS: Forty-one studies were included in this review. The measures used to assess CVD risk were categorized into biochemical, subclinical markers, components of metabolic syndrome, and global risk scores. Compared with noncaregivers, caregivers were more likely to have higher CVD incidence rates and objectively measured risk. Cardiovascular disease risks were also increased by their caregiving experience, including hours/duration of caregiving, caregivers' poor sleep status, psychological symptoms, poor engagement in physical/leisure activities, and care recipient's disease severity. CONCLUSIONS: Although there were limited longitudinal studies in caregivers of patients with diverse health conditions, we found evidence that caregivers are at high risk of CVD. Further research for various caregiver groups using robust methods of measuring CVD risk is needed. Caregiver factors should be considered in developing interventions aimed at reducing CVD risk for caregivers.

Perceived role overload and physical symptom experience among caregivers of older adults: The moderating effect of social support.

We investigated the association between perceived role overload and physical symptom experience, and the potential moderating effect of social support among caregivers of older adults. We analyzed data of 1,471 caregivers obtained from the 2017 National Study of Caregiving. In the survey, participants were assessed for physical symptoms (pain, limited leg strength, and low energy), symptom-related activity limitations, perceived role overload, and informal/formal support sources. We performed multiple logistic regression analyses with interaction terms. Caregivers who perceived higher role overload were more likely to experience the physical symptoms and frequent limited activities due to the symptoms. The associations of perceived role overload with pain and low energy, respectively, were attenuated among caregivers with high informal support. The moderating effect of formal support appeared to be the opposite in relation to pain. Caregivers who perceived high burden may benefit from their informal support to prevent detrimental effects of caregiving on physical health.

Association of a Substance Use Disorder with Infectious Diseases among Adult Home Healthcare Patients with a Venous Access Device.

Substance use disorders (SUDs) and high incidence of infectious diseases are both critical public health issues. Among patients who use a venous access device (VAD) in home care settings, SUDs may play a role in increasing their risk of having a concurrent infectious disease. This study examined the association of SUD with infectious diseases among adult home healthcare patients with a VAD. We identified adult patients with an existing VAD who were admitted to a home healthcare agency August 1, 2017-July 31, 2018 from the electronic health records of a large Medicare-certified agency. Four serious infectious diseases (endocarditis, epidural abscess, septic arthritis, and osteomyelitis) and SUD related to injectable drugs were identified using relevant ICD-10 codes. Multiple logistic regression was performed to examine the association. Of 416 patients with a VAD, 12% (n = 50) had at least one diagnosis of a serious infectious disease. The percentage of patients who had a serious infectious disease was 40% among those with SUDs, compared with only 11% among those without SUDs. After adjusting for age and sex, the odds of having a serious infectious disease was 3.52 times greater for those with SUDs compared with those without (odds ratio [95% confidence interval], 4.52 [1.48-13.79], n = .008). Our findings suggest that home healthcare patients with a VAD and a documented SUD diagnosis may have an increased risk of having a concurrent serious infectious disease. Therefore, patients with an SUD and a VAD would need more attention from home healthcare providers to prevent a serious infectious disease. Further research is suggested on modalities of care for individuals with an SUD and VAD to reduce the incidence of infectious diseases so that care can be delivered safely and efficiently in a home healthcare setting.

A scoping review of racial/ethnic disparities in sleep.

BACKGROUND: Despite remarkable achievements in ensuring health equity, racial/ethnic disparities in sleep still persist and are emerging as a major area of concern. Accumulating evidence has not yet been well characterized from a broad perspective. We conducted a scoping review of studies on sleep disparities by race/ethnicity to summarize characteristics of existing studies and identify evidence gaps. METHODS: We searched PubMed, CINAHL, PsycINFO, and Web of Science databases for studies of racial/ethnic disparities in sleep. Studies that met inclusion criteria were retrieved and organized in a data charting form by study design, sleep measuring methods, sleep features, and racial/ethnic comparisons. RESULTS: One hundred sixteen studies were included in this review. Most studies focused on disparities between Whites and Blacks. Disproportionately fewer studies examined disparities for Hispanic, Asian, and other racial/ethnic groups. Self-reported sleep was most frequently used. Sleep duration, overall sleep quality, and sleep disordered breathing were frequently studied, whereas other features including sleep efficiency, latency, continuity, and architecture were understudied, particularly in racial minority groups in the US. Current study findings on racial/ethnic disparities in most of sleep features is mixed and inconclusive. CONCLUSIONS: This review identified significant evidence gaps in racial/ethnic disparities research on sleep. Our results suggest a need for more studies examining diverse sleep features using standardized and robust measuring methods for more valid comparisons of sleep health in diverse race/ethnicity groups.

A systematic review of interventions for family caregivers who care for patients with advanced cancer at home.

OBJECTIVE: To examine the characteristics of interventions to support family caregivers of patients with advanced cancer. METHODS: Five databases (CINAHL, Medline, PsycINFO, Web of Science, and the Cochrane Library) were searched for English language articles of intervention studies utilizing randomized controlled trials or quasi-experimental designs, reporting caregiver-related outcomes of interventions for family caregivers caring for patients with advanced cancer at home. RESULTS: A total of 11 studies met the inclusion criteria. Based on these studies, the types of interventions were categorized into psychosocial, educational, or both. The characteristics of interventions varied. Most interventions demonstrated statistically significant results of reducing psychological distress and caregiving burden and improving quality of life, self-efficacy, and competence for caregiving. However, there was inconsistency in the use of measures. CONCLUSIONS: Most studies showed positive effects of the interventions on caregiver-specific outcomes, yet direct comparisons of the effectiveness were limited. There is a lack of research aimed to support family caregivers' physical health. PRACTICE IMPLICATIONS: Given caregivers' needs to maintain their wellbeing and the positive effects of support for them, research examining long-term efficacy of interventions and measuring objective health outcomes with rigorous quality of studies is still needed for better outcomes for family caregivers of patients with advanced cancer.

Quality of life among Korean gastrointestinal cancer survivors.

PURPOSE: The number of gastrointestinal (GI) cancer survivors has been steadily increasing owing to early diagnosis and improved cancer treatment outcomes. The quality of life (QoL) of cancer survivors can provide distinct prognostic information and represent their functioning. This study aimed to investigate the levels of symptoms, psychological distress, and QoL of GI cancer survivors, and identify factors associated with QoL. METHOD: A cross-sectional survey was conducted among 145 survivors of gastric or colorectal cancer in a university-affiliated hospital, Seoul, South Korea. The questionnaire consisted of the M. D. Anderson Symptom Inventory Gastrointestinal Cancer Module, Distress Thermometer, and brief version of the World Health Organization Quality of Life Assessment Instrument. Quantile regression was used to assess the associated factors of QoL. The 10th, 25th, 50th, 75th, and 90th conditional quantiles were considered. RESULTS: The most common symptoms were fatigue (24.9%), numbness or tingling (17.2%), feeling bloated (17.2%), dry mouth (15.9%), and difficulty remembering (11.8%). Thirty-two percent (47/145) of the participants reported severe distress. A level of symptoms was significantly associated in the 10th and 25th quantiles, representing poor QoL. Economic burden was a significant influencing factor in all quantiles. CONCLUSION: Our results indicate that high burden from symptoms might be associated with lower QoL in GI cancer survivors, and higher economic burden from cancer treatment was associated with lower QoL. These results suggest that symptom management and support for economic difficulties should be included in the strategies to enhance the QoL of GI cancer survivors.

Cho-kyung-jong-ok-tang, a traditional Korean herbal formula induces type 2 shift in murine natural killer cell cytokine production.

ETHNOPHARMACOLOGICAL RELEVANCE: Cho-kyung-jong-ok-tang (CKJOT) is a traditional Korean herbal formula specifically used for female infertility including unexplained recurrent pregnancy loss (RPL). AIM OF THE STUDY: The present study aims to evaluate the effects of CKJOT on mouse natural killer (NK) cells to address the possible immunological basis of protective effects of this herbal medicine on unexplained RPL. MATERIALS AND METHODS: NK cells isolated from spleens of 6-week-old C57BL/6 mice were differentiated into NK0, NK1, and NK2 cells in the presence of various concentrations of CKJOT-extract. Apoptotic cell number, level of intracellular cytokines, and expression of cytokine-related transcription factors were measured. RESULTS: CKJOT had little effect in improving viability of NK0, NK1, and NK2 cells. However, CKJOT addition during NK cell differentiation suppressed the production of interferon-gamma (IFN-γ), and enhanced that of interleukin-5, in the NK1 and NK2 subsets, respectively. T-bet, a transcription factor associated with IFN-γ expression was down-regulated; while Th2 linked transcription factors (STAT6 and GATA3) were up-regulated especially with 100 µg/mL treatment of CKJOT. CONCLUSION: The type 2 shift in NK cell-secreted cytokines induced by CKJOT in mouse NK cells may explain the protective effect associated with its traditional use in unexplained RPL.

Peroxiredoxin I and II inhibit H2O2-induced cell death in MCF-7 cell lines.

Apoptosis is known to be induced by direct oxidative damage due to oxygen-free radicals or hydrogen peroxide or by their generation in cells by the actions of injurious agents. Together with glutathione peroxidase and catalase, peroxiredoxin (Prx) enzymes play an important role in eliminating peroxides generated during metabolism. We investigated the role of Prx enzymes during cellular response to oxidative stress. Using Prx isoforms-specific antibodies, we investigated the presence of Prx isoforms by immunoblot analysis in cell lysates of the MCF-7 breast cancer cell line. Treatment of MCF-7 with hydrogen peroxide (H2O2) resulted in the dose-dependent expressions of Prx I and II at the protein and mRNA levels. To investigate the physiologic relevance of the Prx I and II expressions induced by H2O2, we compared the survivals of MCF10A normal breast cell line and MCF-7 breast cancer cell line following exposure to H2O2. The treatment of MCF10A with H2O2 resulted in rapid cell death, whereas MCF-7 was resistant to H2O2. In addition, we found that Prx I and II transfection enabled MCF10A cells to resist H2O2-induced cell death. These findings suggest that Prx I and II have important functions as inhibitors of cell death during cellular response to oxidative stress.

BetaPix-a enhances the activity of phospholipase Cgamma1 by binding SH3 domain in breast cancer.

Phospholipase C-gamma1 (PLCgamma1) plays a critical role in cell growth and proliferation by generating the second messengers, diacylglycerol and 1, 4, 5-inositol triphosphate. To investigate the roles of Src homology domain 2 and domain 3 of PLCgamma1 in PLCgamma1-mediated cell signaling, we characterized some proteins binding to these domains in the MCF7 and MDA-MB-231 breast cancer cell lines. Of the several proteins that bind to glutathione-S-transferase-SH2/SH2/SH3, we identified an 85 kDa protein that binds to the SH3 domain of PLCgamma1 as the guanine nucleotide exchange factor, p21-activated protein kinase-interacting exchange factor-a (betaPix-a). BetaPix-a co-immunoprecipitated with PLCgamma1 in breast cancer tissues extracts and in MCF7 and MDA-MB-231 cell extracts. In addition, PDGF-stimulated PLCgamma1 activity was elevated in betaPix-a-overexpressing NIH3T3 cells. Our results suggest that betaPix-a binds to the Src homology domain 3 of PLCgamma1 and promotes tumor growth in breast cancer by enhancing the activity PLCgamma1.

Phospholipase C-protein kinase C mediated phospholipase D activation pathway is involved in tamoxifen induced apoptosis.

Tamoxifen (TAM) is the endocrine therapeutic agent the most widely used in the treatment of breast cancer, and it operates primarily through the induction of apoptosis. In this study, we attempted to elucidate the non-ER mediated mechanism behind TAM treatment, involving the phospholipase C-protein kinase C (PLC-PKC) mediated phospholipase D (PLD) activation pathway, using multimodality methods. In TAM treated MCF7 cells, the PLC and PLD protein and mRNA levels increased. Phosphatidylethanol (PEt) and diacylglycerol (DAG) generation also increased, showing increased activity of PLD and PLCgamma1. Translocation of PKCalpha, from cytosol to membrane, was observed in TAM treated cells. By showing that both PKC and PLC inhibitors could reduce the effects of TAM-induced PLD activation, we confirmed the role of PKC and PLC as upstream regulators of PLD. Finally, we demonstrated that TAM treatment reduced the viability of MCF7 cells and brought about rapid cell death. From these results, we confirmed the hypothesis that TAM induces apoptosis in breast cancer cells, and that the signal transduction pathway, involving PLD, PLC, and PKC, constitutes one of the possible mechanisms underlying the non-ER mediated effects associated with TAM.