order to find a genetic marker to predict the prognosis of patients with
ovarian cancer based on multi-omics data. Methods: We download RNA-Seq
SNP, CNV data and clinical follow-up information from TCGA database and
randomly divide them into training set and test set. GSE17260 dataset in GEO is
taken as an external validation set. Prognosis-related genes, copy number
difference genes and mutant genes are screened in the training set. After the
integration of genes, the random forest algorithm is further used for feature
selection, ultimately obtaining a robust biomarker. On this basis, a
gene-related prognostic model is established and verified in the test set and
verification set. Results: We have obtained 2097 prognostic related
genes, 447 copy amplification genes, 1069 copy deletion genes and 654
significant mutations genes. Through the feature selection of random forest
algorithm, five feature genes (PSMB1, COL6A6, SLC22A2, KLHL23 and CD3G) are
obtained by integrating these genes, some of which have been reported to be
related to tumor progress. Furthermore, the prognostic risk assessment model of
5-gene signature is established by Cox regression analysis. The model can
evaluate the risk of patient samples in training set, test set and external
verification set. 5-gene signature shows strong robustness and clinical
independence. The results of GSEA analysis also show that the pathway of 5-gene
signature enrichment is significantly related to the pathway and biological
process of the occurrence and development of ovarian cancer. Conclusion: In
this study, 5-gene signature is constructed as a new prognostic marker to
predict the survival of patients with ovarian cancer.
Background: Nowadays, acute alcoholic intoxication has become the third public problem in China, and the anti-inebriation products mainly aimed at increasing the activity of enzyme involved in the alcohol metabolism, which is a single mechanism that can accelerate alcohol metabolism. Thus, a new formula, Jiujiuguiyi (JJGY) which could protect liver, relieve the abnormal excitability of the center and improve muscle retardation at the same time is designed by us. Methods: The model of acute alcoholic intoxication was established by intragastric administration with 0.12 ml/10g 50% alcohol in mice. JJGY was orally administrated (gavage) once a day for 20 consecutive days before the establishment of acute alcoholic model. Mice were randomly divided into 8 groups with 8 each: blank control group (CON), model group (M), Haiwangjinzun positive control group (HWJZ), experimental groups (AL, AH, BL, BH, AB). Giant, crawling time on the rota-rod, the activities of aspartate amino trans- ferase (AST), alanine amino transferase (ALT) and superoxide dismutase (SOD) in both liver and serum, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), glutathione peroxidase (GSH-PX) in liver as well as the HE staining of liver slices, the formation of malondialdehyde (MDA) in serum were determined after acute alcoholic intoxication. Results: Compared with model group, JJGY significantly decreased the AST and ALT activity in liver and serum and MDA activity in serum. Meanwhile, it enhanced the ADH and ALDH level in liver as well as the hepatic and serous SOD activity, indicating more efficient metabolism of alcohol and less hepatic injury. HE staining results also proved that JJGY could reduce alcoholic liver cell injury, and the effect was more obvious in the group medicated before alcohol administration. Moreover, JJGY significantly prolonged the crawling time on the rota-rod and improved the gait of mice and the effect was proved to be better than the widely used health product Haiwangjinzun. Conclusions: This study suggests that JJGY is able to protect liver, relieve the abnormal excitability of the center and improve muscle retardation after acute alcoholic intoxication. Its liver protection effect is likely related to its modulation on the alcohol metabolizing and antioxidant enzymes.
In the present study, a new compound Chinese herbal medicine formula, Jiujiuguiyi, was designed by using the medicine and food homology theory. The formula aims at protecting liver, relieving the abnormal excitability of the center and improving muscle retardation at the same time. Acute alcoholic intoxication model in mice was built, then the ethology test and biochemical test were conducted to exam the efficacy of the formula in different preparations. The results suggest that JJGY can protect the acute alcoholic intoxication mice through multiple mechanisms, providing a new way to develop antialcoholismic drug homologous food.
Emerging evidence has demonstrated that Tanshinone IIA (Tan IIA) prevents cardiomyocytes injury, cardiac fibroblasts and atherosclerosis. However, the molecular mechanism underlying the effects of Tan IIA is still unclear. To investigate the role of Tan IIA in inflammatory response in a ROS-NLRP3 inflammasome dependent manner, RAW264.7 cells stimulated with LPS were recruited to produce a cell model of inflammatory response. Our results indicated that the production of NO was significantly increased after stimulated by LPS, and Tan IIA treated significantly decreased the level of NO. The mRNA expression of NLRP3, IL-1β and TNF-α was significantly inhibited by Tan IIA compared with LPS treated cells. The protein expression of NLRP3, IKBα, pp65/p65 and pp38/p38 was significantly decreased by Tan IIA, compared with LPS or LPS+ATP stimulated groups. Meanwhile, Tan IIA significantly inhibited the level of ROS induced by LPS+ATP. And NAC, a ROS inhibitor, could also inhibit the protein expression of NLRP3. Based on these findings, it could be speculated that the mechanism underlying the effect of Tan IIA may involve the regulation of ROS-NF-κB/ P38-NLRP3 pathway. This study further characterized the molecular mechanism of Tan IIA, and provided new thoughts to its clinical therapy.
Tan IIA could inhibit the inflammatory response and NLRP3 expression stimulated by LPS or LPS+ATP. Acetylcysteine (N-acetyl-l-cysteine, NAC), a ROS inhibitor, could inhibit LPS+ATP-induced increase in NLRP3 level. The mechanism underlying the effects of Tan IIA may involve the regulation of ROS-NF-κB/ P38-NLRP3 pathway. This study further characterized the molecular mechanism of Tan IIA, and provided new thoughts to its clinical therapy.
In order to investigate the mechanism of mitochondrial membrane stabilization by Angelica sinensis polysaccharide (ASP) in murine aplastic anemia (AA).ICR mice were randomly divided into control, AA and ASP-treated groups. The AA group mice were treated with 60Coγand intraperitoneal injections of cyclophosphamide and chloramphenicol. The control animals were treated with lead shielding irradiation and saline injection. The treated AA mice were fed with ASP for 2 wk. Mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy, and the transmembrane potential of bone marrow-nucleated cells （BMNC）was examined by fluorescence spectrophotometry. The Cox and MDH contents of the medium were also studied in the three groups.The mitochondrial number and transmembrane potential of BMNC in the bone marrow decreased in the AA group as compared to the control group, but improved in the ASP-treated group as compared to the AA group. Complete mitochondrial cleavage in the ASP-treated group was significantly delayed (P < 0.05) as compared to the AA group. We conclude that ASP might improve mitochondrial membrane stabilization, and suppress the downregulation of transmembrane potential and apoptosis of BMNC in AA.
Acquired deletions of mtDNA and abnormal mitochondrial function are crucial reasons in some blood disease include aplastic anemia. Angelica sinensis helps in tonifying the blood and promoting its circulation via anti-oxidative and neuroprotective effects. In this paper, we demonstrated that Angelica sinensis polysaccharide can improve improve the mitochondrial ultrastructure, and suppress the downregulation of transmembrane potential and apoptosis of myeloid element to cure bone marrow failure.
Quality marker (Q-marker) of Chinese materia medica (CMM) plays an important role in quality control of CMM products. However, its research strategy and technique remain unclear. Based on the fact that quality standard of CMM should be associated with clinical efficacy, taking Jinqi Jiangtang tablet treating type 2 diabetes as an example, the Q-marker related to activity via the reverse analysis of drug metabolism in clinic and traceability of botanic biosynthetic pathways is discovered and validated. Therefore, we proposed a new research strategy of Q-marker of CMM with "Discovery of clinical active constituents as guidance, Reverse analysis of metabolic transformations as link, and Traceability of biosynthesis pathways as key", to improve quality control of CMM products.
Highlights: "Discovery of clinical active constituents as guidance, Reverse analysis of metabolic transformations as link, and Traceability of biosynthesis pathways as key", a new research strategy for discovering quality marker of Chinese materia medica (CMM), promotes quality standard of CMM.
Objective: To investigate the effect of Dingjifumai Decoction (DJFM) on Electrocardiogram (ECG) and sodium potassium pump in rats with ventricular arrhythmia. Methods: Forty healthy male SD rats (200 ± 20g) were randomly divided into blank group, model group, Metoprolol group and DJFM group. Ten rats in each group were fed with normal diet and free drinking water. Each group was given gavage, and the amount of gavage in each group was calculated according to body weight. In the model group, 0.001% Aconitine was injected into the tail vein at 30ug/kg. In the Metoprolol group, Metoprolol suspension was given according to the standard of 5.2mg/kg per day. In the DJFM group, DJFM was given at 17.6g/kg per day. After 2 weeks of administration, the biologic experiment system BL-420F was used to monitor the II lead ECG curve, and the ECG changes were observed and recorded. Then, the left ventricle of the rat was taken, and part of the heart tissue sodium potassium pump was detected. Results: (1) The effect of DJFM on ECG of rats with ventricular arrhythmia: After intravenous injection of aconitine, the incidence of Ventricular Premature beat (VP), Ventricular Tachycardia (VT), Ventricular Fibrillation (VF) in the model group was 100%, suggesting that the model building of rats with ventricular arrhythmia was successful. (2) VP, VT, and VF time: Compared with model group, DJFM group and Metoprolol group can significantly delay the VP, VT and VF, the difference was statistically significant (P < 0.05). The effect of DJFM group and Metoprolol group on delaying the appearance of VP, VT and VF was the same, there was no significant difference (P > 0.05). (3) The effect of DJFM on sodium potassium pump in rat ventricular arrhythmia heart tissues: Compared with the blank group, the sodium potassium pump value in the model group was significantly decreased, and the difference was statistically significant (P < 0.05). Compared with the model group, the sodium potassium pump value of the tissues in the Metoprolol group and the DJFM group increased, and the difference was statistically significant (P < 0.05). There was no significant difference in sodium potassium pump between the Metoprolol group and the DJFM group (P > 0.05). Conclusion: 1. The rat model of ventricular arrhythmia can be successfully prepared by intravenous injection of Aconitine. 2. DJFM can prolong the occurrence time of cardiac arrhythmias caused by aconitine in rats, such as VP, VT, VF, et al. The mechanism may be related to fast Na+ channel, and it may prevent and control arrhythmias by inhibiting Na+ influx and reducing the fast response cellular self-discipline. 3. DJFM can protect the myocardial tissue sodium potassium pump, which can protect the myocardial cells and improve the myocardial metabolism.
Highlights In this study, the effects of Dingjifumai Decoction (DJFM) on Electrocardiogram and sodium potassium pump of rats with ventricular arrhythmia were observed, and the effects and mechanism of DJFM on ventricular arrhythmia were discussed. We found that DJFM can prolong the occurrence time of cardiac arrhythmias caused by aconitine in rats, such as VP, VT, VF, et al. The mechanism may be related to fast Na+ channel, and it may prevent and control arrhythmias by inhibiting Na+ influx and reducing the fast response cellular self-discipline. DJFM can protect the myocardial tissue sodium potassium pump, which can protect the myocardial cells and improve the myocardial metabolism
The research on the dose-effect relationship in Chinese materia medica is delayed due to the complexity of its composition, multi-efficacy, multi-targeting and other factors. Many experts put forward relevant research ideas and methods and worked out more and more research results in literature, experimental and clinical categories because of the progress of statistical methods and scientific and technological means in recent years. In this paper, these results were preliminarily combed to show the basic situation of dose-effect relationship research in Chinese materia medica.
The research on the dose-effect relationship in Chinese materia medica was delayed due to the complexity of its composition, multi-efficacy, multi-targeting and other factors. However, there are more and more research results in literature, experimental and clinical categories because of the progress of statistical methods and scientific and technological means in recent years. This paper aimed to present the current basic situation.
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