Rindomhaley1015

r in medulloblastoma. Strategies to mitigate the risk of radiation-induced lymphopenia should be considered.

Gynostemma pentaphyllum (Thunb.) Makino is a traditional medicine commonly used in China, East Asia and Southeast Asia. In clinic, it is mainly used for hyperlipidemia and antitumor. Its antitumor activity was first recorded in "Illustrated Catalogue of Plants". Gypenosides were the main active ingredients of G. pentaphyllum. The anticancer activity of gypenosides in vivo and in vitro had been widely reported. However, the mechanism of gypenosides in renal cell carcinoma (RCC) still unclear.

In this study, we tried to investigate the active constituents from G. pentaphyllum and potential mechanisms in RCC treatment through network pharmacology and in vitro experiments.

Active compounds and their targets were evaluated and screened through TCMSP and Swiss Target Prediction database. Notably, nine preliminary screened components obtained from database were identified by LC-MS and LC-MS/MS. The targets associated with RCC were obtained from OMIM, TTD and GeneCards database. The PPI network and active compo through Annexin V/PI dual staining assay. find more RT-qPCR showed that gypenosides downregulated the levels of PIK3CA, Akt and mTOR in Caki-1 and 786-O cells. Mechanistically, gypenosides induced apoptosis of RCC cells through regulating PI3K/Akt/mTOR signaling pathway which was implemented though decreasing the phosphorylation level of Akt and mTOR.

Gypenosides induced apoptosis of RCC cells by modulating PI3K/Akt/mTOR signaling pathway.

Gypenosides induced apoptosis of RCC cells by modulating PI3K/Akt/mTOR signaling pathway.

Activation of autophagy has been implicated in cerebral ischiemia/reperfusion (I/R) injury. Salvianolate lyophilized injection (SLI) has been widely used in the clinical treatment of cerebrovascular disease in China. Whether SLI has any influence on the activation of autophagy in cerebral I/R injury remains elusive.

The aim of this study were to assess whether SLI attenuates I/R-induced brain injury and evaluate its associated mechanisms.

Focal cerebral ischaemia was induced by middle cerebral artery occlusion (MCAO). SLI (21mg/kg) was injected intravenously at the beginning of the reperfusion period and 24 and 48h after ischaemia. The effects of SLI on brain injury were detected according to infarct volume, neurological score, brain oedema, and HE and TUNEL staining at 72h post-MCAO. Western blotting was used to detect alterations in the autophagy-relevant proteins LC3, Beclin-1, mTOR, p62, Lamp-1, and CTSD in the ipsilateral cortex at 24 or 72h post-MCAO.

We first demonstrated that SLI significantlyotective effect on cerebral ischaemia/reperfusion injury, which may be mediated by the autophagy-lysosome pathway.The nucleolus functions as the cellular hub for the initiation and early steps of ribosome biogenesis. Ribosomes are key components of the translation machinery and, accordingly, their abundance needs to be adjusted to the cellular energy status. Further, to ensure translational fidelity, the integrity and quality of ribosomes needs to be monitored under conditions of cellular stress. Stressful insults, such as nutrient, genotoxic or proteotoxic stress, interfere with ribosome biogenesis and activate a cellular response referred to as nucleolar stress. This nucleolar stress response typically affects nucleolar integrity and is intricately linked to the activation of protein quality control pathways, including (i) the ubiquitin proteasome system (UPS) and (ii) the autophagy machinery, to restore cellular proteostasis. Here we will review some key features of the nucleolar stress response with a particular focus on the role of the UPS and autophagy in this process.

It is unclear what role does obesity (OB) index play between blood lipid and bone mineral density (BMD).

This study recruited a total of 4,558 Chinese elders >65 years. OB indices waist circumference (WC), body mass index (BMI), waist-hip-ratio (WHR); blood lipid parameters low density lipoprotein (LDL); total cholesterol (TC), triglyceride (TG), and BMDs at femur neck (FN), total hip (TH), and lumbar spine (LS) were measured. The t-test and multiple linear regression analysis were used to detect the differences of variables. Casual inference test (CIT) were performed to test potential mediators underlying the associations between blood lipid and BMD.

The blood lipids were positively associated with BMD (p<0.05) after adjustment of age and sex (Model 1) both in total subjects and in sex-stratified subjects. The CIT showed that OB indices had significant mediation effects on the associations between blood lipid (TG and LDL) and BMD in total subjects and males. Comparably, the correlations of TG and BMD are most likely mediated by BMI and WC.

This study represented the first effort to report that OB indices, especially BMI and WC, served as significant mediators between blood lipid (TG and LDL) and BMD in Chinese elderly.

This study represented the first effort to report that OB indices, especially BMI and WC, served as significant mediators between blood lipid (TG and LDL) and BMD in Chinese elderly.Polycystic ovary syndrome (PCOS), affecting over 10% of women, is associated with insulin resistance, obesity, dyslipidaemia, fatty liver and adipose tissue dysfunction. Its pathogenesis is poorly understood and consequently treatment remains suboptimal. Prenatally androgenized (PA) sheep, a clinically realistic model of PCOS, recapitulate the metabolic problems associated with PCOS. Fibroblast Growth Factor 21 (FGF21) is a metabolic hormone regulating lipid homeostasis, insulin sensitivity, energy balance and adipose tissue function. We therefore investigated the role of FGF21 in the metabolic phenotype of PA sheep. In adolescence PA sheep had decreased hepatic expression and circulating concentrations of FGF21. Adolescent PA sheep show decreased FGF21 signalling in subcutaneous adipose tissue, increased hepatic triglyceride content, trend towards reduced fatty acid oxidation capacity and increased hepatic expression of inflammatory markers. These data parallel studies on FGF21 deficiency, suggesting that FGF21 therapy during adolescence may represent a treatment strategy to mitigate metabolic problems associated with PCOS.

Endogenously produced glucocorticoids exhibit immunomodulating properties and are of pivotal importance for sepsis outcome. Uncontrolled activation of the immune-adrenal crosstalk increases the risk of sepsis-related death. Triggering receptor expressed on myeloid cells-2 (TREM2) is richly expressed on macrophages and has been demonstrated to improve outcome of sepsis by enhancing elimination of pathogens. However, the role and mode of action of macrophage TREM2 on adrenocortical steroidogenesis remains unclear in septic shock.

The acute septic shock model was established by intraperitoneally challenging wild-type (WT) and TREM2 knock-out (Trem2

) mice with lipopolysaccharide (LPS, 30mg/kg). The mice were assessed for TREM2 expression and local inflammation in adrenal gland and for synthesis of corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in vivo. Bone marrow-derived macrophages or macrophage-derived exosomes were isolated from WT and Trem2

mice and were co-cultured withassociate with macrophage-derived exosomes.Acquired drug-resistance, often involving downregulation or mutations in the target protein, is a major caveat in precision medicine. Understanding mechanisms of resistance to therapeutic drugs may unravel strategies to overcome or prevent them. We previously identified phorbol ester (PE) compounds such as TPA that induce Protein Kinase δ (PKCδ), thereby suppressing leukemogenesis. Here we identified erythroleukemia cell lines that resist PEs and showed that reduced PKCδ protein expression underlies drug resistance. Reduced level of PKCδ in resistant cell lines was due to its phosphorylation followed by protein degradation. Indeed, proteasome inhibition prevented PE-induced loss of PKCδ. Accordingly, a combination of TPA and the proteasome inhibitor ALLN significantly suppressed leukemia in a mouse model of leukemia. PKCδ downregulation by TPA was independent of the downstream MAPK/ERK/P38/JNK pathway. Instead, expression of ubiquitin-associated and SH3 domain-containing protein b (Ubash3b) was induced by TPA, which leads to PKCδ protein dephosphorylation and degradation. This specific degradation was blocked by RNAi-mediated depletion of Ubash3b. In drug-sensitive leukemic cells, TPA did not induce Ubash3b, and consequently, PKCδ levels remained high. A PE-resistant cell line derived from PE-treated sensitive cells exhibited very low PKCδ expression. In these drug resistance cells, a Ubash3b independent mechanism led to PKCδ degradation. Thus, PE compounds in combination with proteasome or specific inhibitors for Ubash3b, or other factors can overcome resistance to TPA, leading to durable suppression of leukemic growth. These results identify Ubash3b as a potential target for drug development.Stress exposure increases risk for depressive symptoms. However, there are substantial individual differences in affective responses to stress. High-frequency heart rate variability (HF-HRV), a marker of vagally-mediated parasympathetic activity, has been conceptualized as a psychophysiological index of emotion regulation that may moderate individuals' responses to stress. Using a daily diary design, we tested whether individual differences in resting HF-HRV moderated the association between daily child-related stress and negative affect among a sample of 84 heterosexual couples with preschool-aged children. After controlling for participants' age, gender, socioeconomic status, employment status, and ethnicity, hierarchical linear modeling revealed that resting HF-HRV moderated both the between-person and within-person associations between self-reported child-related stress and daily negative affect. Between-person analyses indicated that the strength of the positive association between mean daily child stress and negative affect across the daily diary period increased with decreasing resting HF-HRV. Similarly, within-person analyses indicated that on days when participants reported more child-related stress than usual, the magnitude of the increase in negative affect on that day was inversely related to resting HF-HRV. Taken together, these findings suggest that lower resting HF-HRV may index vulnerability to stress-related disturbances in negative affect. This increased negative affective response to daily stress may be one pathway through which individuals with lower resting HF-HRV are at increased risk for depressive symptoms over time.Previous studies have found that self-awareness can help people to recruit more cognitive resources, while people with more cognitive resources can better buffer the detrimental effects of negative events. However, it is not clear whether self-awareness can directly buffer the consequences of negative feedback (i.e., reducing neural sensitivity to negative feedback). To explore this issue, we used a scrambled sentence task (SST) to manipulate participants' self-awareness (self vs. other) and investigated whether outcome evaluations in a gambling task are modulated by the self-awareness priming. Event-related brain potentials (ERPs) were recorded while 27 normal adults performed a gambling task. The ERP analysis focused on the feedback-related negativity (FRN), reward positivity (RewP) and P300 component. We found that the self-awareness priming resulted in a smaller FRN response to the losses compared with the other-awareness priming. There was no significant difference in the RewP response to wins between the self-awareness condition and the other-awareness condition.