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Different network pharmacology mechanisms of Danshen-based Fangjis in the treatment of stable angina.
Zhang, GX, Zhang, YY, Zhang, XX, Wang, PQ, Liu, J, Liu, Q, Wang, Z
Acta pharmacologica Sinica. 2018;(6):952-960
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Abstract
Danshen (Salvia miltiorrhiza) preparations such as Danhong injection, Danshen injection, Salvianolate injection, compound Danshen injection and Sodium Tanshinone IIA Sulfonate (STS) injection are widely used in China to treat stable angina (angina pectoris) caused by coronary heart disease. In this study we compared the network pharmacological mechanisms of the 5 Danshen preparations. Following a literature search performed in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) database, China Biology Medicine (CBM) database, China Conference Paper Database, Wanfang Database, VIP Database and Conference Proceedings Citation Index (through January 2015), 444 randomized controlled trial publications detailing the use of the 5 Danshen-based injections for treating stable angina were identified, and their combined data were analyzed using a network meta-analysis. All of the 5 Danshen-based preparations were effective in treating stable angina with clinical improvement rates of 72.4%-91.6% and electrocardiogram (ECG) improvement rates of 54.5%-71.6%. According to both clinical improvement and ECG improvement, the 5 Danshen-based preparations were ranked as follows: Danhong injection > Salvianolate injection > STS injection > compound Danshen injection > Danshen injection. There were no significant differences among the safety profiles of the 5 Danshen preparations. The meta-analysis results were further examined using a network pharmacology approach and functional enrichment analysis, which revealed that Danshen and Danhong injections affected 4 and 15 signaling pathways, respectively, and that the 4 signaling pathways affected by Danshen were a subset of those influenced by Danhong. Therefore, Danhong injection affected some unique signaling pathways that might regulate lipoprotein metabolism, oxidation, and inflammation, and protect vascular endothelia, reflecting the multi-component and multi-target characteristics of this traditional formula and its strengths in treating complex diseases.
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Significantly mutated genes and regulatory pathways in SCLC-a meta-analysis.
Sundaresan, V, Lin, VT, Liang, F, Kaye, FJ, Kawabata-Iwakawa, R, Shiraishi, K, Kohno, T, Yokota, J, Zhou, L
Cancer genetics. 2017;:20-28
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Abstract
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and demands effective targeted therapeutic strategies. In this meta-analysis study, we aim to identify significantly mutated genes and regulatory pathways to help us better understand the progression of SCLC and to identify potential biomarkers. Besides ranking genes based on their mutation frequencies, we sought to identify statistically significant mutations in SCLC with the MutSigCV software. Our analysis identified several genes with relatively low mutation frequency, including PTEN, as highly significant (p < 0.001), suggesting these genes may play an important role in the progression of SCLC. Our results also indicated mutations in genes involved in the axon guidance pathways likely play an important role in SCLC progression. In addition, we observed that the mutation rate was significantly higher in samples with RB1 gene mutated when compared to samples with wild type RB1, suggesting that RB1 status has significant impact on the mutation profile and disease progression in SCLC.
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A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine.
Neri, M, Frustaci, A, Milic, M, Valdiglesias, V, Fini, M, Bonassi, S, Barbanti, P
Cephalalgia : an international journal of headache. 2015;(10):931-7
Abstract
BACKGROUND Oxidative and nitrosative stress are considered key events in the still unclear pathophysiology of migraine. METHODS Studies comparing the level of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed database. Summary estimates of mean ratios (MR) were carried out whenever a minimum of three papers were available. Nineteen studies were included in the meta-analyses, accounting for more than 1000 patients and controls, and compared with existing literature. RESULTS Most studies measuring superoxide dismutase (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes gave null results. On the contrary, plasma levels of thiobarbituric acid reactive substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR of 2.20 (95% CI: 1.65-2.93). As for NOs, no significant results were found in plasma, serum and urine. However, higher levels were shown during attacks, in patients with aura, and an effect of diet was found. The analysis of glutathione precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase inhibitor, gave inconclusive results. CONCLUSIONS The role of the oxidative pathway in migraine is still uncertain. Interesting evidence emerged for TBARS and SOD, and concerning the possible role of diet in the control of NOx levels.
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Identification of pathways for bipolar disorder: a meta-analysis.
Nurnberger, JI, Koller, DL, Jung, J, Edenberg, HJ, Foroud, T, Guella, I, Vawter, MP, Kelsoe, JR, ,
JAMA psychiatry. 2014;(6):657-64
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Abstract
IMPORTANCE Genome-wide investigations provide systematic information regarding the neurobiology of psychiatric disorders. OBJECTIVE To identify biological pathways that contribute to risk for bipolar disorder (BP) using genes with consistent evidence for association in multiple genome-wide association studies (GWAS). DATA SOURCES Four independent data sets with individual genome-wide data available in July 2011 along with all data sets contributed to the Psychiatric Genomics Consortium Bipolar Group by May 2012. A prior meta-analysis was used as a source for brain gene expression data. STUDY SELECTION The 4 published GWAS were included in the initial sample. All independent BP data sets providing genome-wide data in the Psychiatric Genomics Consortium were included as a replication sample. DATA EXTRACTION AND SYNTHESIS We identified 966 genes that contained 2 or more variants associated with BP at P < .05 in 3 of 4 GWAS data sets (n = 12,127 [5253 cases, 6874 controls]). Simulations using 10,000 replicates of these data sets corrected for gene size and allowed the calculation of an empirical P value for each gene; empirically significant genes were entered into a pathway analysis. Each of these pathways was then tested in the replication sample (n = 8396 [3507 cases, 4889 controls]) using gene set enrichment analysis for single-nucleotide polymorphisms. The 226 genes were also compared with results from a meta-analysis of gene expression in the dorsolateral prefrontal cortex. MAIN OUTCOMES AND MEASURES Empirically significant genes and biological pathways. RESULTS Among 966 genes, 226 were empirically significant (P < .05). Seventeen pathways were overrepresented in analyses of the initial data set. Six of the 17 pathways were associated with BP in both the initial and replication samples: corticotropin-releasing hormone signaling, cardiac β-adrenergic signaling, phospholipase C signaling, glutamate receptor signaling, endothelin 1 signaling, and cardiac hypertrophy signaling. Among the 226 genes, 9 differed in expression in the dorsolateral prefrontal cortex in patients with BP: CACNA1C, DTNA, FOXP1, GNG2, ITPR2, LSAMP, NPAS3, NCOA2, and NTRK3. CONCLUSIONS AND RELEVANCE Pathways involved in the genetic predisposition to BP include hormonal regulation, calcium channels, second messenger systems, and glutamate signaling. Gene expression studies implicate neuronal development pathways as well. These results tend to reinforce specific hypotheses regarding BP neurobiology and may provide clues for new approaches to treatment and prevention.