Background/Aims: Long noncoding RNAs (lncRNAs) have recently emerged as novel and potentially promising therapeutic targets in various cancers. However, the expression pattern and biological function ...of lncRNAs in glioma remain largely elusive. In the present study, we investigated the functional role of an lncRNA, small nucleolar RNA host gene 16 (SNHG16), in glioma. Methods: The expression levels of SNHG16 and miR-4518 were measured using qRT-PCR. The relationship between the levels of SNHG16 and clinicopathologic features were statically analyzed. The levels of proteins were detected using western blot. Bioinformatics analysis and luciferase reporter assays were applied to the analysis of the relationship between SNHG16, miR-4518 and PRMT5. Cell viability and apoptosis were measured using MTT and apoptosis ELISA assay, respectively. Results: SNHG16 was highly expressed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. Knockdown of SNHG16 inhibits the viability and induces apoptosis of glioma cells. Further investigation revealed that SNHG16 could up-regulate the expression of miR-4518 targeted gene PRMT5 via acting as an endogenous sponge of miR-4518. Moreover, SNHG16 also affects the expression of Bcl-2 family proteins and the activation of PI3K/Akt signaling pathway. Conclusion: Our study revealed a novel SNHG16-miR-4518-PRMT5 pathway regulatory axis in glioma pathogenesis. SNHG16 could be used as a potential therapeutic target in the treatment of glioma.
20(S)‐Protopanaxadiol (PPD) is a basic aglycone of the dammarane triterpenoid saponins and exerts antidepressant‐like effects on behaviour in the forced swimming test (FST) and tail suspension test ...(TST) and in rat olfactory bulbectomy depression models. However, the antidepressant effects of PPD have not been studied thoroughly. The objective of the present study was first to investigate the effect of PPD on depression behaviours induced by chronic social defeat stress (CSDS) in mice. The results showed that CSDS was effective in producing depression‐like behaviours in mice, as indicated by decreased responses in the social interaction test, sucrose preference test, TST, and FST, and that this effect was accompanied by noticeable alterations in the levels of oxidative markers (superoxide dismutase, catalase, and lipid peroxidation) and monoamines (5‐HT and NE) in the hippocampus and serum corticosterone levels. Additionally, western blot analysis revealed that CSDS exposure significantly downregulated BDNF, p‐TrkB/TrkB, p‐Akt/Akt, and p‐mTOR/mTOR protein expression in the hippocampus. Remarkably, chronic PPD treatment significantly ameliorated these behavioral and biochemical alterations associated withCSDS‐induced depression. Our results suggest that PPD exerts antidepressant‐like effects in mice with CSDS‐induced depression and that this effect may be mediated by the normalization of neurotransmitter and corticosterone levels and the alleviation of oxidative stress, as well as the enhancement of the PI3K/Akt/mTOR‐mediated BDNF/TrkB pathway.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Testicular dysfunction (TDF) is characterized by testosterone deficiency and is caused by oxidative stress injury in Leydig cells. A natural fatty amide named N-benzylhexadecanamide (NBH), derived ...from cruciferous maca, has been shown to promote testosterone production. Our study aims to reveal the anti-TDF effect of NBH and explore its potential mechanism in vitro. This study examined the effects of H
O
on cell viability and testosterone levels in mouse Leydig cells (TM3) under oxidative stress. In addition, cell metabolomics analysis based on UPLC-Q-Exactive-MS/MS showed that NBH was mainly involved in arginine biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, the TCA cycle and other metabolic pathways by affecting 23 differential metabolites, including arginine and phenylalanine. Furthermore, we also performed network pharmacological analysis to observe the key protein targets in NBH treatment. The results showed that its role was to up-regulate ALOX5, down-regulate CYP1A2, and play a role in promoting testicular activity by participating in the steroid hormone biosynthesis pathway. In summary, our study not only provides new insights into the biochemical mechanisms of natural compounds in the treatment of TDF, but also provides a research strategy that integrates cell metabolomics and network pharmacology in order to promote the screening of new drugs for the treatment of TDF.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Depression is a common, dysthymic, and psychiatric disorder, resulting in enormous social and economic burden. Dammarane sapogenins (DS), an active fraction from oriental ginseng, has shown ...antidepressant‐like effects in chronic restraint rats and sleep interruption‐induced mice, and the present study aimed to further confirm the antidepressant effects of DS in a model of chronic unpredictable mild stress (CUMS) and to explore the underlying mechanism. Oral administration of DS (20, 40, and 80 mg/kg) markedly improved depressant‐like behaviors, increasing the sucrose intake in the sucrose preference test and reducing the latency in the novelty‐suppressed feeding test, and decreasing the immobility time in both the tail suspension and forced swimming tests, compared with the CUMS mice. Biochemical analysis of brain tissue and serum showed that DS treatment restored the decreased hippocampal neurotransmitter concentrations of serotonin, dopamine, norepinephrine (noradrenaline), and gamma‐aminobutyric acid, and decreased the elevated of serum hormone levels (corticotrophin releasing factor, adrenocorticotrophic hormone, and corticosterone) induced by CUMS. Our findings confirm that DS exerts an antidepressant‐like effect in the CUMS model of depression in mice, and suggest it may be mediated by regulation of neurotransmitters and hypothalamic–pituitary–adrenal axis.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
As an alternative terpenoid producer, non-conventional oleaginous yeast
Yarrowia lipolytica
was chosen for limonene production.
Y. lipolytica
can give high biomass yield and metabolize a broad range ...of substrates such as glycerol, alkanes, fatty acid, fats, and oils. As previously reported, optimization of limonene synthesis pathway and mevalonate (MVA) pathway leads to the accumulation of 112-fold higher limonene as compared to an initial strain. In this study, we introduced an additional copy of limonene synthesis gene (
LS
), which resulted in an increase of limonene production. This engineered strain was used to carry out further optimization study. Amongst all the carbon sources tested, the highest level of limonene production was obtained from glycerol, and citrate was selected as an auxiliary carbon source. In fed-batch fermentation with an optimized medium, the engineered strain was found to produce 165.3 mg/L limonene, which corresponds to the highest yield till date for the production of limonene in
Y. lipolytica.
As an effective medicine for jaundice in traditional Chinese medicine, Cucumis melo L. has been widely used in China. However, its effect on vascular function is still unclear. In this study, we ...extracted the compounds of Cucumis melo L., and the major ingredients were identified as cucurbitacins (CuEC, cucurbitacins extracted from Cucumis melo L.), especially cucurbitacin B. We replicated the toxicity in mice by intraperitoneal injection of a high dose of CuEC (2 mg/kg) and demonstrated that the cause of death was CuEC-induced impairment of the endothelial barrier and, thus, increased vascular permeability via decreasing VE-cadherin conjunction. The administration of low doses of CuEC (1 mg/kg) led to a decline in systolic blood pressure (SBP) without causing toxicity in mice. More importantly, CuEC dramatically suppressed angiotensin II (Ang II)-induced SBP increase. Further studies demonstrated that CuEC facilitated acetylcholine-mediated vasodilation in mesenteric arteries of mice. In vitro studies showed that CuEC induced vasodilation in a dose-dependent manner in mesenteric arteries of both mice and rats. Pretreatment with CuEC inhibited phenylephrine-mediated vasoconstriction. In summary, a moderate dose of CuEC reduced SBP by improving blood vessel tension. Therefore, our study provides new experimental evidence for developing new antihypertensive drugs.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The neuroprotective properties of ginsenosides have been found to reverse the neurological damage caused by oxidation in many neurodegenerative diseases. However, the distribution of ginsenosides in ...different tissues of the main root, which was regarded as the primary medicinal portion in clinical practice was different, the specific parts and specific components against neural oxidative damage were not clear. The present study aims to screen and determine the potential compounds in different parts of the main root in ginseng. Comparison of the protective effects in the main root, phloem and xylem of ginseng on hydrogen peroxide-induced cell death of SH-SY5Y neurons was investigated. UPLC-Q-Exactive-MS/MS was used to quickly and comprehensively characterize the chemical compositions of the active parts. Network pharmacology combined with a molecular docking approach was employed to virtually screen for disease-related targets and potential active compounds. By comparing the changes before and after Content-Effect weighting, the compounds with stronger anti-nerve oxidative damage activity were screened out more accurately. Finally, the activity of the selected monomer components was verified. The results suggested that the phloem of ginseng was the most effective part. There were 19 effective compounds and 14 core targets, and enriched signaling pathway and biological functions were predicted. After Content-Effect weighting, compounds Ginsenosides F1, Ginsenosides Rf, Ginsenosides Rg
and Ginsenosides Rd were screened out as potential active compounds against neural oxidative damage. The activity verification study indicated that all four predicted ginsenosides were effective in protecting SH-SY5Y cells from oxidative injury. The four compounds can be further investigated as potential lead compounds for neurodegenerative diseases. This also provides a combined virtual and practical method for the simple and rapid screening of active ingredients in natural products.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose:
To develop a model to select appropriate candidates for irradiation stent placement among patients with unresectable pancreatic cancer with malignant biliary obstruction (UPC-MBO).
Methods:
...This retrospective study included 106 patients treated with an irradiation stent for UPC-MBO. These patients were randomly divided into a training group (74 patients) and a validation group (32 patients). A clinical model for predicting restenosis-free survival (RFS) was developed with clinical predictors selected by univariate and multivariate analyses. After integrating the radiomics signature, a combined model was constructed to predict RFS. The predictive performance was evaluated with the concordance index (C-index) in both the training and validation groups. The median risk score of progression in the training group was used to divide patients into high- and low-risk subgroups.
Results:
Radiomics features were integrated with clinical predictors to develop a combined model. The predictive performance was better in the combined model (C-index, 0.791 and 0.779 in the training and validation groups, respectively) than in the clinical model (C-index, 0.673 and 0.667 in the training and validation groups, respectively). According to the median risk score of 1.264, the RFS was significantly different between the high- and low-risk groups (
p
< 0.001 for the training group, and
p
= 0.016 for the validation group).
Conclusions:
The radiomics-based model had good performance for RFS prediction in patients with UPC-MBO who received an irradiation stent. Patients with slow progression should consider undergoing irradiation stent placement for a longer RFS.
Hepatocellular carcinoma (HCC) remains an incurable disease with a very poor clinical outcome. The purpose of this article was to investigate whether the expression or methylation of tetrapeptide ...repeat domain 36 (TTC36) could be used as a prognostic marker in hepatocellular carcinoma. TCGA database was used to obtain information on HCC gene expression and the associated clinical features of HCC patients. Differentially expressed genes (DEGs) were screened between 374 HCC specimens and 50 nontumor specimens. The expression and prognostic value of TTC36 were analyzed. The correlations between TTC36 and cancer immune infiltrates were investigated via TIMER. In this study, HCC specimens and nontumor specimens were compared and 35 DEGs were found between them. Among the 35 DEGs, the expression of TTC36 was significantly reduced in HCC samples compared with nontumor samples. Survival tests revealed that patients with low TTC36 expression had a shorter overall survival than patients with high TTC36 expression. TTC36 was found to be an independent predictive factor for HCC in both univariate and multivariate regression analyses. TTC36 was negatively regulated by TTC36 methylation, leading to its low expression in HCC tissues. Immune analysis revealed that TTC36 expression has significant correlations with B cell, T cell CD4+, neutrophil, macrophage, and myeloid dendritic cell. Finally, TTC36 expression was dramatically reduced in HCC cells, and overexpression greatly suppressed HCC cell proliferation and invasion, according to our experimental results. Overall, our data suggested that TTC36 could be applied as a prognostic marker for predicting outcome and immune infiltration in HCC.
Full text
Available for:
DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
•DS reverses depression-like behavior in chronic social defeat stress-induced mice.•DS promoted the hippocampal neurogenesis and expression of BDNF.•DS improved the TrkB/CREB/ERK pathway and the ...PI3K/AKT/mTOR pathway.
Chronic social defeat stress (CSDS) is a widely used behavioural paradigm of psychosocial stress that can be used to research the pathogenesis of depression and seek antidepressant drugs. Dammarane sapogenins (DS), the deglycosylated product of ginsenosides, has a wide range of biological activities, including immunomodulatory, antifatigue, antitumour and antidepressant activities. However, whether DS has antidepressant-like effects in a CSDS mouse model remains unknown. Therefore, the present study was conducted to evaluate the antidepressant properties of DS in CSDS mice and its underlying mechanisms. The results showed that the oral administration of DS (40 and 80 mg/kg) increased the time spent in the interaction zone in the social interaction test and the sucrose intake in the sucrose preference test, decreased the latency in the novelty-suppressed feeding test, and reduced the immobility time in both the tail suspension test and forced swimming test. Biochemical analyses of brain tissue and serum showed that DS treatment significantly decreased serum corticosterone levels and enhanced brain monoamine neurotransmitter levels in CSDS mice. In addition, an impairment in hippocampal neurogenesis that paralleled a reduced BDNF level in the hippocampus was observed in the mice that were subjected with CSDS for 3 weeks, while treatment with DS reversed these changes. Moreover, DS treatment significantly upregulated BDNF, pTrkB/TrkB, pAkt/Akt, pPI3K/PI3K, pCREB/CREB, pERK1/2/ERK1/2 and pmTOR/mTOR protein expression in the hippocampus. In conclusion, our results showed that DS exerts antidepressant-like effects in mice with CSDS-induced depression, that the effects may be mediated by the normalization of monoamine neurotransmitter levels, the prevention of HPA axis dysfunction and the impairment of hippocampal neurogenesis, and that this occurs partly through the ability of DS to enhance BDNF expression by increasing the TrkB/CREB/ERK pathway and the PI3K/AKT/mTOR pathway.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
