Moderation Effects of Positive Core Belief and Social-Emotional Responsiveness on the Relationship Between Cyberbullying Victimization and Affective Symptoms.

Introduction: Medical students are a vulnerable population. Exposure to cyberbullying can aggravate stress and lead to affective disorders. Features that moderate the influence of this stressor have been under-studied in Thai context. Materials and Methods: An annual survey on the mental health and stressors of medical students from 2021 was analyzed. Measures on cyberbullying victimization, psychosocial stressors, self-reported resilience measures ("problem solving", "positive core belief", "social emotional responsiveness", and "perseverance"), and other covariates were assessed for their effects on affective symptoms using linear regression. Interaction analyses were then performed. Results: A total of 303 cyberbullied respondents were included. In a linear regression model controlled for cyberbullying victimization score, perceived psychosocial difficulties, age, and academic year, positive core belief significantly predicted lower affective symptoms, while social-emotional responsiveness showed a trend toward predicting lower affective symptoms. Trend toward negative interaction was found for positive core belief, whereas an opposite trend was found for social-emotional responsiveness. Implications in the context of medical schools are also discussed. Discussion: Positive core belief appears to be a resilience feature toward cyberbullying victimization in the studied population. Its effects were discussed from the perspective of cognitive-behavioral therapy. In the context of medical school, the belief could be fostered by creating a safe learning environment with readily available guidance. Social-emotional responsiveness is a protective factor toward cyberbullying victimization, although its trend toward negative interaction with cyberbullying victimization implies that this feature's protective effect declines as intensity of the bullying increases. Conclusion: Positive core belief is a potential resilience feature of cyberbullying victimization. On the other hand, the protective effect of social-emotional responsiveness appeared to decline with greater intensity of cyberbullying.

Sonicated Extract from the Aril of Momordica Cochinchinensis Inhibits Cell Proliferation and Migration in Aggressive Prostate Cancer Cells.

Momordica cochinchinensis or gac fruit has been reported to have several biological activities, including antioxidation, anti-inflammatory, and anticancer activities. However, the effect on cancer cell metastasis has not been extensively studied. With this aim, the extract from the aril part was selected and investigated for prostate cancer cell migration. The aril extracts were prepared as boiled extract, sonicated extract, ethanol extract, and HAE (hexane:acetone:ethanol; 2 : 1 : 1) extract, while the prostate cancer cell models were PC-3 and LNCaP cells. An MTT assay was performed to compare the antiproliferative effect between prostate cancer cells and normal Vero cells. As a result, the sonicated extract had the highest efficiency in PC-3 cells, with IC50 values of 2 mg/mL and 0.59 mg/mL for 48 and 72 h, respectively, while it had less of an effect in LNCaP cells and was not toxic to normal cells. Cell damage was further confirmed using LDH and cell cycle analysis. As a result, the sonicated extract did not cause cell damage or death and only inhibited cell proliferation. The effect on cancer metastasis was further examined by wound healing, transwell migration assays, and western blotting. The results demonstrated that the sonicated extract inhibited PC-3 cell migration and decreased MMP-9 but increased TIMP-1 expression. All these results support that gac fruit is a valuable source for further development as an anticancer agent for prostate cancer patients.

An adiponectin-S1P axis protects against lipid induced insulin resistance and cardiomyocyte cell death via reduction of oxidative stress.

BACKGROUND: Adiponectin exerts several beneficial cardiovascular effects, however their specific molecular mechanisms require additional understanding. This study investigated the mechanisms of adiponectin action in the heart during high fat diet (HFD) feeding or in palmitate (PA) treated H9c2 cardiomyoblasts. METHODS: 6-week-old male adiponectin knock out (Ad-KO) mice were fed chow or 60% HFD for 6 weeks then received saline or recombinant adiponectin (3µg/g body weight) for an additional 2 weeks. After acute insulin stimulation (4 U/kg), tissue and serum samples were collected for analysis. H9c2 cardiomyocytes were treated ±0.1 mM PA, the adiponectin receptor agonist AdipoRon, or the antioxidant MnTBAP then assays to analyze reactive oxygen species (ROS) production and cell death were conducted. To specifically determine the mechanistic role of S1P, gain and loss of function studies were conducted with adding S1P to cells or the inhibitors THI and SKI-II, respectively. RESULTS: HFD feeding induced cardiac insulin resistance in Ad-KO mice, which was reversed following replenishment of normal circulating adiponectin levels. In addition, myocardial total triglyceride was elevated by HFD and lipidomic analysis showed increased levels of ceramides and sphingosine-1-phosphate (S1P), with only the latter being corrected by adiponectin administration. Similarly, treatment of H9C2 cardiomyoblasts with PA led to a significant increase of intracellular S1P but not in conditioned media whereas AdipoRon significantly increased S1P production and secretion from cells. AdipoRon or the antioxidant MnTBAP significantly reduced PA-induced cell death. Gain and loss of function studies suggested S1P secretion and autocrine receptor activation mediated the effect of AdipoRon to attenuate PA-induced ROS production and cell death. CONCLUSION: Our data establish adiponectin signaling-mediated increase in S1P secretion as a mechanism via which HFD or PA induced cardiomyocyte lipotoxicity, leading to insulin resistance and cell death, is attenuated.

Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action.

Adiponectin mediates anti-diabetic effects via increasing hepatic insulin sensitivity and direct metabolic effects. In the present study, we conducted a comprehensive and unbiased metabolomic profiling of liver tissue from AdKO (adiponectin-knockout) mice, with and without adiponectin supplementation, fed on an HFD (high-fat diet) to derive insight into the mechanisms and consequences of insulin resistance. Hepatic lipid accumulation and insulin resistance induced by the HFD were reduced by adiponectin. The HFD significantly altered levels of 147 metabolites, and bioinformatic analysis indicated that one of the most striking changes was the profile of increased lysophospholipids. These changes were largely corrected by adiponectin, at least in part via direct regulation of PLA2 (phospholipase A2) as palmitate-induced PLA2 activation was attenuated by adiponectin in primary hepatocytes. Notable decreases in several glycerolipids after the HFD were reversed by adiponectin, which also corrected elevations in several diacyglycerol and ceramide species. Our data also indicate that stimulation of ω-oxidation of fatty acids by the HFD is enhanced by adiponectin. In conclusion, this metabolomic profiling approach in AdKO mice identified important targets of adiponectin action, including PLA2, to regulate lysophospholipid metabolism and ω-oxidation of fatty acids.

A bibliometric analysis of diets and breast cancer research.

Breast cancer is the most common cancer among women worldwide. The primary aim of this work was to provide an in-depth evaluation of research publications in the field of diets and breast cancer. The impact of economic outcome on national academic productivity was also investigated. Data were retrieved using Pubmed for English-language publications. The search included all research for which articles included words relating to "diets and breast cancer". Population and national income data were obtained from publicly available databases. Impact factors for journals were obtained from Journal Citation Reports® (Thomson Scientific). There were 2,396 publications from 60 countries in 384 journals with an impact factor. Among them, 1,652 (68.94%) publications were Original articles. The United States had the highest quantity (51% of total) and highest of mean impact factor (8.852) for publication. Sweden had the highest productivity of publication when adjusted for number of population (6 publications per million population). Publications from the Asian nation increased from 5.3% in 2006 to 14.6% in 2012. The Original article type was also associated with geography (p<0.001; OR=2.183; 95%CI=1.526-3.123), Asian countries produced more proportion of Original articles (82%) than those of rest of the world (67.6%). Diets and breast cancer-associated research output continues to increase annually worldwide including publications from Asian countries. Although the United States produced the most publications, European nations per capita were higher in publication output.

Adiponectin mediated APPL1-AMPK signaling induces cell migration, MMP activation, and collagen remodeling in cardiac fibroblasts.

Defects in adiponectin action have been implicated in the development of cardiac dysfunction in obesity and diabetes. Cardiac fibroblasts play an important role in regulating extracellular matrix remodeling yet little is known regarding the direct effects of adiponectin on cardiac fibroblasts. In this study, we first demonstrated temporal relocalization of cellular APPL1 in response to adiponectin in primary cardiac fibroblasts and that siRNA-mediated knockdown of APPL1 attenuated stimulation of AMPK by adiponectin. The cell surface content of MT1-MMP and activation of MMP2 were induced by adiponectin and these responses were dependent on AMPK signaling. Enhanced MMP activity facilitated increased fibroblast migration in response to adiponectin which was also prevented by inhibition of AMPK, with no change in cell proliferation observed. Collagen and elastin immunofluorescence demonstrated reorganization of the extracellular matrix in accordance with increased MMP activity, whereas quantitative mRNA analysis, (3) H-proline incorporation and picrosirius red assays showed no change in intracellular or extracellular total collagen levels in response to adiponectin. In summary, these data are the first to report the adiponectin stimulated APPL1-AMPK signaling axis in cardiac fibroblasts and characterize MT1-MMP translocation, MMP2 activity and cell migration as functional outcomes. These effects may be of significance in heart failure associated with obesity and diabetes.

ID4 gene polymorphism and osteoporosis in Thai menopausal women.

BACKGROUND: The inhibitor of DNA binding 4 (ID4) protein regulates osteogenic and adipogenic cell fate and lack of lD4 gene expression decreased osteoblast differentiation. Variant in the ID4 gene polymorphism has not been reported with osteoporosis. OBJECTIVE: To identify whether ID4 can be a marker gene for osteoporosis in Thai menopausal women. MATERIAL AND METHOD: The 3 'UTR of lD4 (rs3798339) single nucleotide polymorphism was examined bypolymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP), together with lumbar spine bone mineral density (BAMD) in 160 Thai menopausal women. RESULTS: Lumbar spine 3 (L3) had a significantly lower BMD score in women with the TT genotype, compared with the CT+CC genotypes (p = 0.037). This disappeared after the adjustment of various factors. CONCLUSION: The polymorphism at 3'UTR of lD4 gene can alter ID4 mRNA stability, and may be linked to the function of proteins. However, this needs confirmation in larger populations. The present study is useful as an initial investigation into ID4 gene polymorphism in osteoporosis.