Effect of Laughter Therapy on Mood Disturbances, Pain, and Burnout in Terminally Ill Cancer Patients and Family Caregivers.

BACKGROUND: Humor has been commonly used in palliative care and identified as a coping strategy of palliative care patients and family caregivers. However, the use of humor or laughter in palliative care settings is still limited. OBJECTIVE: The aim of this study was to examine the effect of laughter therapy involving spontaneous laughter on mood disturbances and pain in terminally ill patients with cancer and mood disturbances and the levels of burnout in family caregivers. METHODS: This quasi-experimental study used a nonequivalent control group pretest-posttest design. The laughter therapy developed was provided for 20 to 30 minutes a day for 5 consecutive days. Twenty-six pairs of terminally ill cancer patients and family caregivers in the intervention group and 23 pairs in the comparison group from the hospice ward of a tertiary teaching hospital participated in this study. The data were collected using structured questionnaires and analyzed using descriptive statistics and 2-way repeated-measures analysis of variance. RESULTS: There were significant decreases in mood disturbances in the patients ( P < .001) and family caregivers ( P < .001), pain in the patients ( P < .001), and levels of burnout in the caregivers ( P < .001) in the intervention group. CONCLUSION: Laughter therapy can be an alternative intervention to support both terminally ill patients with cancer and their family caregivers experiencing multidimensional distress in palliative care settings. IMPLICATIONS FOR PRACTICE: The appropriate use of laughter or humor therapy needs to be encouraged as a support tool in palliative care. Palliative care teams must be properly trained to provide spontaneous laughter therapy or planned humor therapy.

Momordica charantia Ethanol Extract Attenuates H2O2-Induced Cell Death by Its Antioxidant and Anti-Apoptotic Properties in Human Neuroblastoma SK-N-MC Cells.

Oxidative stress, which is induced by reactive oxygen species (ROS), causes cellular damage which contributes to the pathogenesis of neurodegenerative diseases. Momordica charantia (MC), a traditional medicinal plant, is known to have a variety of health benefits, such as antidiabetic, anti-inflammatory, and antioxidant effects. However, it is unknown whether MC has protective effects against oxidative stress-induced neuronal cell death. The aim of this study was to investigate the potential action of MC on oxidative stress induced by H2O2. First, we tested whether the pretreatment of Momordica charantia ethanol extract (MCEE) attenuates H2O2-induced cell death in human neuroblastoma SK-N-MC cells. MCEE pretreatment significantly improved cell viability and apoptosis that deteriorated by H2O2. Further, MCEE ameliorated the imbalance between intracellular ROS production and removal through the enhancement of the intracellular antioxidant system. Intriguingly, the inhibition of apoptosis was followed by the blockage of mitochondria-dependent cell death cascades and suppression of the phosphorylation of the mitogen-activated protein kinase signaling (MAPKs) pathway by MCEE. Taken together, MCEE was shown to be effective in protecting against H2O2-induced cell death through its antioxidant and anti-apoptotic properties.

Major compounds of red ginseng oil attenuate Aß25-35-induced neuronal apoptosis and inflammation by modulating MAPK/NF-κB pathway.

ß-Amyloid (Aß)-induced neuronal toxicity in Alzheimer's disease (AD) is associated with complex mechanisms. Thus, a multi-target approach might be suitable for AD treatment. Following our previous study on the neuroprotective effects of red ginseng oil extract, its major compounds, including linoleic acid (LA), ß-sitosterol (BS), and stigmasterol (SS), were examined to elucidate the mechanism of anti-apoptosis and anti-inflammation in Aß25-35-stimulated PC12 cells. The results showed that the three compounds mitigated Aß25-35 toxicity by regulating oxidative stress, apoptotic responses, and pro-inflammatory mediators. LA and SS strongly regulated intrinsic apoptosis markers, such as mitochondrial membrane potential, intracellular Ca2+, Bax/Bcl-2 ratio, and caspases-9, -3, and -8. However, BS blocked only the intrinsic apoptotic pathway, particularly by suppressing Ca2+ accumulation. Furthermore, all three compounds downregulated iNOS and phospho-nuclear factor-κB, but only LA and SS inhibited the expression of cyclooxygenase-2 and phospho-IκB. In assays to evaluate MAPK expression for confirming upstream signal pathways, BS decreased the phosphorylation of p38 and ERK, but not JNK, while SS markedly decreased the phosphorylation of all three MAPKs, and LA clearly decreased the phosphorylation of ERK and JNK, but not p38. These results indicate that LA, BS, and SS act as neuroprotectives against Aß25-35-induced injury by distinct molecular mechanisms, indicating their preventive and/or therapeutic potential to treat AD.

BACE1 Inhibition by Genistein: Biological Evaluation, Kinetic Analysis, and Molecular Docking Simulation.

ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) plays a role in generating amyloid ß (Aß), thus playing a major part early in the pathogenesis of Alzheimer's disease (AD). BACE1 has emerged as a crucial therapeutic target for decreasing the Aß concentration in the AD brain. To explore natural BACE1 inhibitors, the present study concentrated on isoflavones, including genistein, formononetin, glycitein, daidzein, and puerarin. In this study, in vitro anti-AD activities were assessed using BACE1 inhibition assays, as well as enzyme kinetic predictions. Molecular docking analysis was applied to design potential BACE1 inhibitors. Among the major isoflavones, genistein exerted a notable BACE1 inhibition through reversible noncompetitive mechanism, while other compounds were less potent against BACE1. The docking study revealed that genistein had negative binding energy (-8.5 kcal/mol) and was stably positioned in the allosteric domains of BACE1 residues. It interacted with important amino acid residues in BACE1, such as ASN37, GLN73, and TRP76, through hydrogen bonding. The results suggested that genistein may be beneficial for preventing and/or treating AD. Furthermore, it may provide potential guidelines for the design of new BACE1 inhibitors.

Protective Effects of Red Ginseng Oil against Aß25-35-Induced Neuronal Apoptosis and Inflammation in PC12 Cells.

One of pathological characteristics of Alzheimer's disease (AD), aggregation and deposition of ß amyloid (Aß), has been accepted as a potent activator of neuronal cell death. Red ginseng is well-known for various pharmacological activities, but most studies have been focused on red ginseng water extract (RGW), which has resulted in the conception of the present study of red ginseng oil (RGO) against Aß25-35-induced neurotoxicity. Cytotoxicity and apoptosis induction by Aß were verified and the underlying mechanism by which RGO inhibited neuronal cell death, mitochondria dysfunction and NF-κB pathway related protein markers were evaluated. RGO attenuated Aß25-35-induced apoptosis, not only by inhibiting calcium influx, but also by reducing mitochondrial membrane potential loss. RGO significantly decreased Bax, whereas increased Bcl-2 and inactivated of caspase-3 and -9 and PARP-1 stimulated by Aß25-35. Anti-neuroinflammatory effect of RGO was demonstrated by downregulating c-Jun N-terminal kinase (JNK) and p38, resulting in inhibiting of the NF-κB pathway and thereby suppressing the expressions of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nitric oxide (NO) and tumor necrosis factor-α (TNF-α). The present study revealed that RGO is a potential natural resource of the functional foods industry as well as a promising candidate of multi-target neuronal protective agent for the prevention of AD.

Protective Role of Corilagin on Aß25-35-Induced Neurotoxicity: Suppression of NF-κB Signaling Pathway.

Aggregation and deposition of beta-amyloid peptides (Aß), a pathological hallmark of Alzheimer's disease, has been recognized as a potent activator of neuroinflammation and neuronal dysfunction. In this study, the underlying molecular mechanisms responsible for the neuroprotective effects of corilagin against Aß25-35-triggered neurotoxicity and inflammatory responses were investigated in PC12 cells. Pretreatment with corilagin effectively protected PC12 cells against Aß25-35-induced damage and apoptosis. Aß25-35 induced damage in PC12 cells as revealed by increased production of reactive oxygen species, caspase-3 activity, and cell cycle arrest was attenuated by corilagin pretreatment. Corilagin not only significantly suppressed the production of neurotoxic inflammatory mediators such as tumor necrosis factor-α, nitric oxide, and prostaglandin E2 but also downregulated cyclooxygenase-2 and inducible nitric oxide synthase expression in PC12 cells. It also exerted a beneficial effect by suppressing the degradation of inhibitor of κB (IκB)-α and subsequent activation of transcription factor nuclear factor κB (NF-κB), mostly through inhibition of extracellular signal-regulated kinase activity in comparison to c-Jun N-terminal kinase and p38 MAP kinase (p38) mitogen-activated protein kinase activity. These findings suggest that attenuation of Aß25-35-induced inflammatory responses by downregulating the NF-κB signaling pathway might be a valuable strategy for both Alzheimer's disease prevention and/or treatment.