Cardiomyocyte-specific inactivation of thyroid hormone in pathologic ventricular hypertrophy: an adaptative response or part of the problem?

Recent studies in various rodent models of pathologic ventricular hypertrophy report the re-expression of deiodinase type 3 (D3) in cardiomyocytes. D3 inactivates thyroid hormone (T3) and is mainly expressed in tissues during development. The stimulation of D3 activity in ventricular hypertrophy and subsequent heart failure is associated with severe impairment of cardiac T3 signaling. Hypoxia-induced signaling appears to drive D3 expression in the hypertrophic cardiomyocyte, but other signaling cascades implicated in hypertrophy are also capable of stimulating transcription of the DIO3 gene. Many cardiac genes are transcriptionally regulated by T3 and impairment of T3 signaling will not only reduce energy turnover, but also lead to changes in gene expression that contribute to contractile dysfunction in pathologic remodeling. Whether stimulation of D3 activity and the ensuing local T3-deficiency is an adaptive response of the stressed heart or part of the pathologic signaling network leading to heart failure, remains to be established

Chatbots as Peer Counselors in Helping DLSU Senior High School Students Manage Their Stress: Socio-Technical Requirements

Pressure to perform well academically and relationships with family and friends cause varying degrees of stress among students that can affect the functionality and stability of their mental health. One of the known solutions in reducing stress is peer counseling where experiences and hardships are shared with trusted peers in order to receive support from one another. Peer counseling has benefitted the support seeker and the support providers who are involved in the peer counseling session. The advancement of technology has made significant development in the application of accessible technologies in healthcare, including mental health. The use of chatbots has been recently introduced as well as its potential in serving as an alternative platform to help individuals cope with stress and manage their well-being. In this study, senior high school students of De La Salle University were interviewed to identify the causes of their stress, to determine the strategies they employ in managing their stress with particular emphasis on peer counseling, and to solicit feedback on their perception in using a chatbot as a peer counselor. Findings from this study may provide insights on the ideal characteristics of a chatbot as a peer counselor that can inform future designers of such technologies to support stress management

S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase

S6 kinase (S6K) deletion in metazoans causes small cell size, insulin hypersensitivity, and metabolic adaptations; however, the underlying molecular mechanisms are unclear. Here we show that S6K-deficient skeletal muscle cells have increased AMP and inorganic phosphate levels relative to ATP and phosphocreatine, causing AMP-activated protein kinase (AMPK) upregulation. Energy stress and muscle cell atrophy are specifically triggered by the S6K1 deletion, independent of S6K2 activity. Two known AMPK-dependent functions, mitochondrial biogenesis and fatty acid beta-oxidation, are upregulated in S6K-deficient muscle cells, leading to a sharp depletion of lipid content, while glycogen stores are spared. Strikingly, AMPK inhibition in S6K-deficient cells restores cell growth and sensitivity to nutrient signals. These data indicate that S6K1 controls the energy state of the cell and the AMPK-dependent metabolic program, providing a mechanism for cell mass accumulation under high-calorie diet

Sex-specific cardiac cardiolipin remodelling after doxorubicin treatment

BACKGROUND: Imbalance in lipid metabolism and membrane lipid homeostasis has been observed in numerous diseases including heart failure and cardiotoxicity. Growing evidence links phospholipid alterations especially cardiolipins (CLs) to defects in mitochondrial function and energy metabolism in heart failure. We have shown recently that doxorubicin cardiotoxicity is more severe in male than female Wistar rats. We aimed to study whether this sex specificity is linked to differences in cardiac phospholipid profiles. RESULTS: Adult male and female rats were injected 2 mg/kg doxorubicin weekly for 7 weeks. Cardiac phospholipid molecular species were determined by liquid chromatography coupled with mass spectrometry fragmentation (LC)/MS(n). Sex difference in phosphatidylethanolamine and phosphatidylcholine species containing docosahexaenoic and docosapentaenoic acyl chains was observed, females having more than males. In both sexes, doxorubicin induced an important loss of the main CL(18:2)(4), while the level of monolysocardiolipin MLCL(18:2)(3) remained stable. However, a severe remodelling appeared in treated rats with the longest CL acyl chains in doxorubicin-treated females, which might compensate for the loss of tetra-linoleoyl CL. The level of oxidized cardiolipin was not particularly increased after doxorubicin treatment. Finally, expression of genes involved in the biosynthesis of fatty acid appeared to be decreased in doxorubicin-treated males. CONCLUSIONS: These results emphasize for the first time the cardiac remodelling in the phospholipid classes after doxorubicin treatment. These observations suggest that doxorubicin has a sex-specific impact on the heart phospholipidome especially on cardiolipin, an essential mitochondrial lipid. Further studies are needed to better understand the roles of lipids in the anthracycline cardiotoxicity and sex differences, but phospholipid cardioprotection seems a valuable new additive therapeutic strategy for anthracycline cardiotoxicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13293-015-0039-5) contains supplementary material, which is available to authorized users