Our study aims to explore the active components and mechanisms of the Danshen-Guizhi drug pair in treating ovarian cancer by network pharmacology and in vitro experiment. The “component-target-pathway” diagram of the Danshen-Guizhi drug pair was established by network pharmacology, and the effective active components, important targets as well as potential mechanisms of the Danshen-Guizhi drug pair were analyzed. The predicted results were verified by molecular docking and in vitro experiments. The main active components of the Danshen-Guizhi drug pair in the treatment of ovarian cancer are salviolone, luteolin, β-sitosterol and tanshinone IIA. The main core target is PTGS2. The pathways involved mainly include the cancer pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. The molecular docking results showed that salviolone and tanshinone IIA had good binding ability to the target. The expression of PTGS2 mRNA and PGE2 in ovarian cells were significantly inhibited by salviolone. The mechanism of the Danshen-Guizhi drug pair in the treatment of ovarian cancer may be regulating cell proliferation, apoptosis and tumor immunity. This provides a theoretical basis for the clinical development and application of the Danshen-Guizhi drug pair.
ObjectiveLittoral cell angioma (LCA) is currently considered to be a rare splenic tumor with malignant potential. As the epidemiology, pathogenesis, clinical manifestation, treatment, and prognosis remain unclear, the clinical diagnosis and treatment of LCA have not been standardized. Hence, we performed a comprehensive analysis of 189 observational studies comprising 435 patients to improve the current status of diagnosis and treatment.MethodsPubMed, Embase, WanFang and CNKI were searched from inception to May 2021 to identify LCA studies that were published in English and Chinese. The clinical information of LCA patients were extracted and analyzed.ResultsThe LCA has a male-to-female ratio of 0.90 and a solitary-to-multiple ratio of 0.31. In terms of clinical features, 69.7% of the patients showed splenomegaly, 49.7% were asymptomatic, and 39.2% experienced epigastric discomfort. As the imaging findings of patients with LCA were nonspecific, an image-guided biopsy (10/12) was a safe and effective method for diagnosing in this condition. Notably, results of the prognostic analysis indicated that LCA has a lower risk of recurrence and metastasis. The patient may develop a stable disease or the tumor will grow but will not metastasize. Besides, the novel immunohistochemical pattern of LCA was described as CD31+/ERG+/FVIII Antigen+/CD68+/CD163+/lysozyme+/CD8−/WT1−.ConclusionLCA should be reconsidered as a benign primary splenic vascular neoplasm, which is more like an intra-splenic manifestation of abnormal body function. Image-guided biopsy with follow-up might be a beneficial choice for LCA patients. For LCA patients with abdominal discomfort, pathological uncertainty or continuous tumor enlargement, splenectomy remains the preferred treatment.
This is the first report of the distribution frequencies of functional CYP1A2, CYP2B6 and iNOS genes among mainland Chinese Tibetan, Mongolian, Uygur and Han populations. These results should help inform studies of interethnic differences in disease susceptibility or drug responses.
Genetic polymorphisms that are associated with drug-metabolising enzymes can cause variation in disease susceptibility and drug responses. 1 Cytochrome P450 3A (CYP3A) oxidises almost half of all clinically prescribed drugs (e.g., tacrolimus, cyclosporine, nifedipine, midazolam, and glucocorticoids). A CYP3A gene cluster is located on chromosome 7q22.1 and spans a 231 kilobase (kb) genomic region that includes four genes (CYP3A4, CYP3A5, CYP3A7, and CYP3A43) and two pseudogenes (CYP3AP1 and CYP3AP2). 2 CYP3A7 is the most abundant CYP3A in fetal liver but its levels usually decrease drastically at birth, after which the isoform is replaced by CYP3A4. 3 However, the fetal isoform has also been found to be polymorphically expressed in a cohort of adult livers and has been associated with the CYP3A7*1C allele, which contains seven completely linked single-base mutations in the CYP3A7 promoter region (−291G > T, [4][5][6] Because the transcription factors pregnane X receptor and constitutively activated receptor bind with higher affinity to the promoter of CYP3A7*1C than to that of wild-type CYP3A7, the CYP3A7*1C allele is associated with higher CYP3A7 mRNA and protein expression. Recently, CYP3A7*1C was also found to be
Genetic variations of cytochrome P450 (CYP) influence the inter‐individual differences in drug response. Here, we collected 8682 variants of 57 CYP genes and cytochrome P450 oxidoreductase (POR) from a large‐scale sequencing project in Chinese, Chinese Millionome Database (CMDB). In addition, 52 294 variants from the Genome Aggregation Database (gnomAD) had been simultaneously identified and analysed. Rare variants with a variant allele frequency (VAF) < 0.01 comprised 41.4% (3594/8682) of identified variations in the CMDB, while 98.1% (51 320/52 294) in the gnomAD were rare. Out of 8682 variants in the CMDB, 66.9% (5808/8682) were in introns and only 4.3% (377/8682) were missense variants. In contrast, 36.2% (18 929/52 294) variants in the gnomAD were missense. The common alleles with a VAF over 0.1 were found in CYP1A2*1C, CYP1A2*1F, CYP2C19*2, CYP2D6*2, CYP2D6*10, CYP3A5*3 and CYP4F2*3, with a VAF of 0.161, 0.6, 0.27, 0.274, 0.678, 0.92 and 0.233, respectively. The growing number of genetic variations in CYP genes as more genomes are sequenced would increase the power to predict drug metabolism and response based on the genotype of the particular individual.
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