Dignity, Resilience, and Quality of Life in Patients With Cardiac Disease: A Partial Least Squares Structural Equation Modeling Approach.

BACKGROUND: Health-related quality of life (HRQoL) is an important indicator of patient's satisfaction about their disease course. Many factors are influential to life quality, such as dignity and resilience. Dignity is mostly explored in populations with cancer, but the understanding of dignity and its relationship with resilience and HRQoL is limited. OBJECTIVE: The aim of this study was to explore the relationships between dignity, resilience, and HRQoL among patients with cardiac disease. METHODS: A purposive sample of patients with cardiac disease with a cross-sectional design was used for this study. Four structured questionnaires were used for data collection. Dignity was measured by the Patient Dignity Inventory-Mandarin version; resilience was measured by the Chinese version of the Resilience Scale; HRQoL was measured by EuroQol 5 Dimensions. Partial least squares structural equation modeling was applied to test the hypothesized structural model. Reporting was consistent with the Strengthening the Reporting of Observational Studies in Epidemiology checklist. RESULTS: The mean age of all 101 participants was 72.2 years, 88.1% had coronary artery disease, and the prevalence of heart failure was 43.0%. In patients with cardiac disease, their sense of dignity was significantly associated with HRQoL, and resilience was associated with both dignity and quality of life. Notably, resilience had a mediating effect between dignity and HRQoL; dignity and resilience explained 73.0% of the variance of HRQoL. CONCLUSIONS: Dignity is a new concern in cardiac disease research, which is influential to patients' perception of disease and their HRQoL. Patients with cardiac disease with higher resilience tend to have a better HRQoL.

Beneficial Effect of Astragaloside on Alzheimer's Disease Condition Using Cultured Primary Cortical Cells Under ß-amyloid Exposure.

ß-amyloid (Aß)-mediated neuronal apoptosis contributes to the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether astragalosides (AST) could inhibit Aß-induced apoptosis in vivo and in vitro and to explore the underlying mechanisms. Amyloid ß-protein fragment 25-35 (Aß25-35) was administered to cerebral lateral ventricle of rats to make the AD models in vivo. AST was able to attenuate both cortical cell degeneration and memory deficits in the AD rats. AST also inhibited Aß25-35-induced cytotoxicity (e.g., decreased cell viability); apoptosis (e.g., increased caspase-3 expression, increased DNA fragmentation, and Tau hyperphosphorylation); synaptotoxicity (e.g., increased loss of both a dendritic marker, microtubule-associated protein 2 (MAP-2) and synaptic proteins, synaptophysins); and mitochondrial dysfunction (e.g., increased mitochondrial membrane potential) in cultured primary rat cortical cells. The beneficial effect of AST in reducing Aß-induced cytotoxicity, apoptosis, and mitochondrial dysfunction in cortical cells were blocked by inhibition of phosphoinositide 3-kinase (PI3K)-dependent protein kinase B (PKB, as known as AKT) activation with LY294002. In addition, inhibition of extracellular protein kinase (ERK) with U0126 shared with the AST the same beneficial effects in reducing Aß-induced apoptosis. Our data suggest that the cortical PI3K/AKT and MAPK (or ERK) pathways as appealing therapeutic targets in treating AD, and AST may have a positive impact on AD treatment via modulation of both PI3K/AKT and ERK pathways.

Cathepsin B is involved in the heat shock induced cardiomyocytes apoptosis as well as the anti-apoptosis effect of HSP-70.

Cathepsin B is one of the major lysosomal cysteine proteases that plays an important role in apoptosis. Herein, we investigated whether Cathepsin B is involved in cardiomyocyte apoptosis caused by hyperthermic injury (HI) and heat shock protein (HSP)-70 protects these cells from HI-induced apoptosis mediated by Cathepsin. HI was produced in H9C2 cells by putting them in a circulating 43 °C water bath for 120 min, whereas preinduction of HSP-70 was produced in H9C2 cells by mild heat preconditioning (or putting them in 42 °C water bath for 30 min) 8 h before the start of HI. It was found that HI caused both cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. E-64-c, in addition to reducing Cathepsin B activity, significantly attenuated HI-induced cardiomyocyte apoptosis (evidenced by increased apoptotic cell numbers, increased tuncated Bid (t-Bid), increased cytochrome C, increased caspase-9/-3, and decreased Bcl-2/Bax) in H9C2 cells. In addition, preinduction of HSP-70 by mild heat preconditioning or inhibition of HSP-70 by Tripolide significantly attenuated or exacerbated respectively both the cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. Furthermore, the beneficial effects of pre-induction of HSP-70 by mild heat production in reducing both cardiomyocyte apoptosis and increased Cathepsin B activity caused by HI can be significantly reduced by Triptolide preconditioning. These results indicate that Cathepsin B is involved in HI-induced cardiomyocyte apoptosis in H9C2 cells and HSP-70 protects these cells from HI-induced cardiomyocyte apoptosis through Cathepsin B pathways.

Melatonin improves outcomes of heatstroke in mice by reducing brain inflammation and oxidative damage and multiple organ dysfunction.

We report here that when untreated mice underwent heat stress, they displayed thermoregulatory deficit (e.g., animals display hypothermia during room temperature exposure), brain (or hypothalamic) inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment (e.g., decreased plasma levels of both adrenocorticotrophic hormone and corticosterone during heat stress), multiple organ dysfunction or failure, and lethality. Melatonin therapy significantly reduced the thermoregulatory deficit, brain inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment, multiple organ dysfunction, and lethality caused by heat stroke. Our data indicate that melatonin may improve outcomes of heat stroke by reducing brain inflammation, oxidative damage, and multiple organ dysfunction.

Attenuating heat-induced cellular autophagy, apoptosis and damage in H9c2 cardiomyocytes by pre-inducing HSP70 with heat shock preconditioning.

PURPOSE: We sought to assess whether heat-induced autophagy, apoptosis and cell damage in H9c2 cells can be affected by pre-inducing HSP70 (heat shock protein 70). MATERIALS AND METHODS: Cell viability was determined using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide staining and a lactate dehydrogenase assay. Apoptosis was evidenced using both flow cytometry and counting caspase-3 positive cells, whereas autophagy was evidenced by the increased LC3-II expression and lysosomal activity. RESULTS: The viability of H9c2 cells was temperature-dependently (40-44 °C) and time-dependently (90-180 min) significantly (p < 0.05) reduced by severe heat, which caused cell damage, apoptosis and autophagy. Heat-induced cell injury could be attenuated by pretreatment with 3-methylademine (an autophagy inhibitor) or Z-DEVD-FMK (a caspase-3 inhibitor). Neither apoptosis nor autophagy over the levels found in normothermic controls was induced in heat-shock preconditioned controls (no subsequent heat injury). The beneficial effects of mild heat preconditioning (preventing heat-induced cell damage, apoptosis and autophagy) were significantly attenuated by inhibiting HSP70 overexpression with triptolide (Tripterygium wilfordii) pretreatment. CONCLUSION: We conclude that pre-inducing HSP70 attenuates heat-stimulated cell autophagy, apoptosis and damage in the heart. However, this requires in vivo confirmation.

Brain cooling causes attenuation of cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke.

The purpose of the present study was to assess the therapeutic effect of hypothermic retrograde jugular vein flush (HRJVF) on heatstroke. HRJVF was accomplished by infusion of 4 degrees C isotonic sodium chloride solution via the external jugular vein (1.7 mL/100 g of body weight over 5 min). Immediately after the onset of heatstroke, anesthetized rats were divided into 2 major groups and given the following: 36 degrees C or 4 degrees C isotonic sodium chloride solution, i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. When the 36 degrees C saline-treated rats underwent heat exposure, their survival time values were found to be 23 to 28 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline significantly improved survival during heatstroke (208-252 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time, and d-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase; and striatal levels of glycerol, glutamate, and lactate/pyruvate; dihydroxy benzoic acid, lipid peroxidation, oxidized-form glutathione reduced-form glutathione, dopamine, and serotonin were all elevated during heatstroke. Core and brain temperatures and intracranial pressure were also increased during heatstroke. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and striatal levels of local blood flow, partial pressure of oxygen, superoxide dismutase, catalase, glutathione peroxidase, and glutathions reductase activities were all significantly lower during heatstroke. The circulatory dysfunction, systemic inflammation, hypercoagulable state, and cerebral oxidative stress, ischemia, and damage during heatstroke were all significantly suppressed by HRJVF. These findings demonstrate that brain cooling caused by HRJVF therapy may resuscitate persons who had a stroke by attenuating cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke.