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#34124490   2021/05/25 To Up

Study on the Mechanism of the Danggui-Chuanxiong Herb Pair on Treating Thrombus through Network Pharmacology and Zebrafish Models.

Danggui-Chuanxiong (DC) is a commonly used nourishing and activating blood medicine pair in many gynecological prescriptions and modern Chinese medicine. However, its activating blood mechanism has not been clearly elucidated. Our research aimed at investigating the activating blood mechanisms of DC using network pharmacology and zebrafish experiments. Network pharmacology was used to excavate the potential targets and mechanisms of DC in treating thrombus. The antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis activities of DC and the main components of DC, ferulic acid (DC2), ligustilide (DC7), and levistilide A (DC17), were evaluated by zebrafish models in vivo. A total of 24 compounds were selected as the active ingredients with favorable pharmacological parameters for this herb pair. A total of 89 targets and 18 pathways related to the thrombus process were gathered for active compounds. The genes, TNF, CXCR4, IL2, ESR1, FGF2, HIF1A, CXCL8, AR, FOS, MMP2, MMP9, STAT3, and RHOA, might be the main targets for this herb pair to exert cardiovascular activity from the analysis of protein-protein interaction and KEGG pathway results, which were mainly related to inflammation, vasculogenesis, immunity, hormones, and so forth. The zebrafish experiment results showed that DC had antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis activities. The main compounds had different effects of zebrafish activities. Especially, the antithrombotic activity of the DC17H group, anti-inflammatory activities of DCH and DC2H groups, antioxidant activities of DCM, DCH, DC2, DC7, and DC17 groups, and vasculogenesis activities of DCM, DCH, and DC2 groups were stronger than those of the positive group. The integrated method coupled zebrafish models with network pharmacology provided the insights into the mechanisms of DC in treating thrombus.
Mengqi Zhang, Peihai Li, Shanshan Zhang, Xuanming Zhang, Lizhen Wang, Yun Zhang, Xiaobin Li, Kechun Liu

2366 related Products with: Study on the Mechanism of the Danggui-Chuanxiong Herb Pair on Treating Thrombus through Network Pharmacology and Zebrafish Models.

2 ml Ready-to-use 100ul2.5 mg100 U0.2 mg100.00 ul1 ml1100ug 6 ml Ready-to-use 200 units

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#34119408   2021/06/09 To Up

Nonclassical androgen and estrogen signaling is essential for normal spermatogenesis.

Signaling by androgens through androgen receptor (AR) is essential to complete spermatogenesis in the testis. Similarly, loss of the main estrogen receptor, estrogen receptor 1 (ESR1; also known as ERα), results in male infertility, due in part to indirect deleterious effects on the seminiferous epithelium and spermatogenesis. Effects of steroid hormones are induced primarily through genomic changes induced by hormone-mediated activation of their intracellular receptors and subsequent effects on nuclear gene transcription. However, androgens and estrogens also signal through rapid nonclassical pathways involving actions initiated at the cell membrane. Here we review the data that nonclassical androgen and estrogen signaling pathways support processes essential for male fertility in the testis and reproductive tract. The recent development of transgenic mice lacking nonclassical AR or ESR1 signaling but retaining genomic nuclear signaling has provided a powerful tool to elucidate the function of nonclassical signaling in the overall response to androgens and estrogens. Results from these mice have emphasized that nonclassical signaling is essential for full responses to these hormones, and absence of either nonclassical or classical AR or ESR1 pathways produces abnormalities in spermatogenesis and the male reproductive tract. Although additional work is required to fully understand how classical and nonclassical receptor signaling synergize to produce full steroid hormone responses, here we summarize the known physiological functions of the classical and nonclassical androgen and estrogen signaling pathways in the testis and reproductive tract.
Paul S Cooke, William H Walker

2342 related Products with: Nonclassical androgen and estrogen signaling is essential for normal spermatogenesis.

25 μg50 ug 5mg100ug0.1 mg100ug100ul0.1ml (1mg/ml)0.25 mg1 g25 μg

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#34105210   2021/06/08 To Up

Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases.

Among breast carcinoma patients with metastatic disease, 15-30% will eventually develop brain metastases. We examined the genomic landscape of a large cohort of breast carcinoma brain metastases (BCBMs) and compared them to a cohort of primary breast carcinomas (BCs).
Richard S P Huang, James Haberberger, Kimberly McGregor, Douglas A Mata, Brennan Decker, Matthew C Hiemenz, Mirna Lechpammer, Natalie Danziger, Kelsie Schiavone, James Creeden, Ryon P Graf, Roy Strowd, Glenn J Lesser, Evangelia D Razis, Rupert Bartsch, Athina Giannoudis, Talvinder Bhogal, Nancy U Lin, Lajos Pusztai, Jeffrey S Ross, Carlo Palmieri, Shakti H Ramkissoon

1377 related Products with: Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases.



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#34102428   2021/06/01 To Up

(Re-)activity in the caregiving situation: Genetic diversity within Oxytocin-Vasopressin Pathway is associated with salivary oxytocin and vasopressin concentrations in response to contact with a crying infant-simulator.

Oxytocin (OT) and vasopressin (AVP) hormones as well as their receptors (OXTR and AVPR1a) have been deemed crucial for caregiving and sensitive responsiveness to infant cues. However, previous research on genetic polymorphisms and OT and AVP levels in the context of caregiving were sparse and have brought contradictory findings. The aim of this reported observational study was to examine the impact of genetic variations within genes related to OT and AVP signaling pathway on hormones levels' changes in response to the caregiving situation. A total of 221 adult intimate couples (110 childless, non-pregnant and 111 expectant couples) participated in three 10 min sessions, during which they were taking care of a crying life-like simulator. 30 min prior to the first session salivary samples to analyze basal OT and AVP, and polymorphisms in OXTR, AVPR1a and CD38 genes were collected. Subsequent OT and AVP levels were measured 15 min after each session. The two most frequently studied OXTR SNPs (rs53576 and rs2254298) had no or a minor impact on higher OT levels, which were linked to rs1042778, rs13316193, rs2228485, rs2268490, rs4686302 genotypes. AVP levels were affected by rs1042778, rs13316193, rs4686302 and rs237887. OT levels varied depending on the OT (rs2770378, rs4813625), CD38 (rs379686), and 5-HTR2A (rs6314) genotype. OT and AVP levels were also associated with rs6314 (5-HTR2A). AVP levels were linked to ESR1 (rs1884051) and SIM1 (rs3734354) variations. Shorter variants of RS3 and RS1 were associated with lower levels of AVP. In conclusion, analyzed polymorphisms were associated with both the level and changes in OT and AVP hormone levels in the standardized situation of caregiving reactions to infant crying.
Magda Rybicka, Maria Kaźmierczak, Paulina Pawlicka, Ariadna Beata Łada-Maśko, Paulina Anikiej-Wiczenbach, Krzysztof Piotr Bielawski

2324 related Products with: (Re-)activity in the caregiving situation: Genetic diversity within Oxytocin-Vasopressin Pathway is associated with salivary oxytocin and vasopressin concentrations in response to contact with a crying infant-simulator.

1 kit0.1ml (1mg/ml)1 kit2 Pieces/Box100ug Lyophilized96 assays 100ug Lyophilized100ug Lyophilized

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#34101078   2021/06/08 To Up

Evaluation of endocrine resistance using ESR1 genotyping of circulating tumor cells and plasma DNA.

Therapeutic efficacy of hormonal therapies to target estrogen receptor (ER)-positive breast cancer is limited by the acquisition of ligand-independent ESR1 mutations, which confer treatment resistance to aromatase inhibitors (AIs). Monitoring for the emergence of such mutations may enable individualized therapy. We thus assessed CTC- and ctDNA-based detection of ESR1 mutations with the aim of evaluating non-invasive approaches for the determination of endocrine resistance.
Tilak K Sundaresan, Taronish D Dubash, Zongli Zheng, Aditya Bardia, Ben S Wittner, Nicola Aceto, Erin J Silva, Douglas B Fox, Matthew Liebers, Ravi Kapur, John Iafrate, Mehmet Toner, Shyamala Maheswaran, Daniel A Haber

2220 related Products with: Evaluation of endocrine resistance using ESR1 genotyping of circulating tumor cells and plasma DNA.

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#34097174   2021/06/07 To Up

Comparison of two targeted ultra-deep sequencing technologies for analysis of plasma circulating tumour DNA in endocrine-therapy-resistant breast cancer patients.

There is growing interest in the application of circulating tumour DNA (ctDNA) as a sensitive tool for monitoring tumour evolution and guiding targeted therapy in patients with cancer. However, robust comparisons of different platform technologies are still required. Here we compared the InVisionSeq™ ctDNA Assay with the Oncomine™ Breast cfDNA Assay to assess their concordance and feasibility for the detection of mutations in plasma at low (< 0.5%) variant allele fraction (VAF).
Georgios Nteliopoulos, Karen Page, Allison Hills, Karen Howarth, Warren Emmett, Emma Green, Luke J Martinson, Daniel Fernadez-Garcia, Robert Hastings, David S Guttery, Laura Kenny, Justin Stebbing, Susan Cleator, Farah Rehman, Kelly L T Gleason, Andrijac Sanela, Charlotte Ion, Amelia J Rushton, Nitzan Rosenfeld, R Charles Coombes, Jacqueline A Shaw

1328 related Products with: Comparison of two targeted ultra-deep sequencing technologies for analysis of plasma circulating tumour DNA in endocrine-therapy-resistant breast cancer patients.

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#34096606   2021/06/07 To Up

YAP, CTGF and Cyr61 are overexpressed in tamoxifen-resistant breast cancer and induce transcriptional repression of ERα.

About 70% of breast cancers overexpress estrogen receptor α (ERα, encoded by ESR1). Tamoxifen, a competitive inhibitor of estrogen that binds to ER, has been widely used as a treatment for ER-positive breast cancer. However, 20-30% of breast cancer is resistant to tamoxifen treatment. The mechanisms underlying tamoxifen resistance remain elusive. We found that Yes-associated protein (YAP; also known as YAP1), connective tissue growth factor (CTGF; also known as CCN2) and cysteine-rich angiogenic inducer 61 (Cyr61; also known as CCN1) are overexpressed, while ERα is downregulated in tamoxifen-resistant breast cancer. Inhibition of YAP, CTGF and Cyr61 restored ERα expression and increased sensitivity to tamoxifen. Overexpression of YAP, CTGF, and Cyr61 led to downregulation of ERα and conferred resistance to tamoxifen in ER-positive breast cancer cells. Mechanistically, CTGF and Cyr61 downregulated ERα expression at the transcriptional level by directly binding to the regulatory regions of the ERα-encoding gene, leading to increased tamoxifen resistance. Also, CTGF induced Glut3 (also known as SLC2A3) expression, leading to increased glycolysis, which enhanced cell proliferation and migration in tamoxifen-resistant cells. Together, these results demonstrate a novel role of YAP, CTGF and Cyr61 in tamoxifen resistance and provide a molecular basis for their function in tamoxifen-resistant breast cancer.
Hyungjoo Kim, Seogho Son, Yunhyo Ko, Jeong Eon Lee, Sangmin Kim, Incheol Shin

1760 related Products with: YAP, CTGF and Cyr61 are overexpressed in tamoxifen-resistant breast cancer and induce transcriptional repression of ERα.



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#34094972   2021/05/19 To Up

Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues.

Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a prominent impact in the pathogenesis of breast cancer. Among the transcription factors associated with ESR signaling, FOXM1, GATA3, FOXA1 and ESR1 have been suggested as a candidate in the pathogenesis of this neoplasm. In the current project, we have designed an approach to find long non-coding RNAs (lncRNAs) that regulate these transcription factors. Then, we used clinical samples to carry out validation of our in silico findings. Our systems biology method led to the identification of , , , , and lncRNAs. Subsequently, we assessed the expression of these genes in breast cancer tissues compared with the adjacent non-cancerous tissues (ANCTs). Expression of was significantly higher in breast cancer tissues compared with ANCTs (Ratio of mean expressions (RME) = 4.99, P value = 3.12E-04). Moreover, expression levels of , , and were elevated in breast cancer tissues compared with control tissues (RME = 2.27, P value = 5.40E-03; Ratio of mean expressions = 615.95, P value = 7.39E-19 and RME = 1.78, P value = 3.40E-02, respectively). On the other hand, the expression of was lower in breast cancer tissues than controls (RME = 0.31, P value = 1.87E-03). Expression levels of , , and and were not significantly different between the two sets of samples. Expression of was significantly associated with stage (P value = 4.77E-02). Moreover, expressions of and were associated with the mitotic rate (P values = 2.18E-02 and 1.77E-02, respectively). Finally, expressions of and were associated with breastfeeding duration (P values = 3.88E-02 and 4.33E-02, respectively). Based on the area under receiver operating characteristics curves, had the optimal diagnostic power in differentiating between cancerous and non-cancerous tissues (AUC = 0.95, Sensitivity = 0.90, Specificity = 0.96). The combination of expression levels of all genes slightly increased the diagnostic power (AUC = 0.96). While there were several significant pairwise correlations between expression levels of genes in non-tumoral tissues, the most robust correlation was identified between and (r = 0.61, P value = 3.08E-8). In the breast cancer tissues, the strongest correlations were reported between / and / pairs (r = 0.51, P value = 4.79E-5 and r = 0.51, P value = 6.39E-5, respectively). The current investigation suggests future assessment of the functional role of , and in the development of breast neoplasms.
Bita Hassani, Mohammad Taheri, Yazdan Asgari, Ali Zekri, Ali Sattari, Soudeh Ghafouri-Fard, Farkhondeh Pouresmaeili

2798 related Products with: Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues.

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#34087554   2021/05/26 To Up

Effects of continuous and intermittent cadmium exposure on HPGL axis, GH/IGF axis and circadian rhythm signaling and their consequences on reproduction in female zebrafish: Biomarkers independent of exposure regimes.

Typical biomarkers of cadmium (Cd) pollution have well been confirmed in fish from continuous exposure pattern. However, in a natural environment, fish may be exposed to Cd intermittently. In this study, juvenile female zebrafish were exposed for 48 days to 10 μg/L Cd continuously, 20 μg/L for 1 day in every 2 days or 30 μg/L for 1 day in every 3 days. The toxic effects were evaluated using 8 various physiological and biochemical endpoints like specific growth rate (SGR), 17β-estradiol (E2) and vitellogenin (VTG) concentrations in plasma, reproductive parameters (gonadosomatic index (GSI), egg-laying amount, spawning percentage, and hatching and mortality rate of embryos). Transcription of 59 genes related to hypothalamic-pituitary-gonadal-liver (HPGL) axis, circadian rhythm signaling and insulin-like growth factor (IGF) system was examined. SGR, spawning percentage, E2 and VTG levels declined in fish exposed to 10 and 20 μg/L Cd but remained relatively stable in fish exposed to 30 μg/L Cd. Exposure to 10, 20 and 30 μg/L Cd significantly reduced GSI, hatching rate and mortality rate. Similarly, mRNA expression of 27 genes were sensitive to both continuous and intermittent Cd exposure. Among these genes, expression levels of 10 genes had more than 5-fold increase or decrease, including mRNA levels of vtg1, vtg2, vtg3, esr1, igf2a, igf2b, igfbp5b, nr1d1, gnrh3 and gnrhr4. The most sensitive molecular biomarker was vtg3 expression with 1500-3100 fold increase in the liver. The present study, for the first time, provides effective candidate biomarkers for Cd, which are independent of exposure regimes.
Jia-Lang Zheng, Li-Bin Peng, Li-Ping Xia, Jiji Li, Qing-Ling Zhu

2676 related Products with: Effects of continuous and intermittent cadmium exposure on HPGL axis, GH/IGF axis and circadian rhythm signaling and their consequences on reproduction in female zebrafish: Biomarkers independent of exposure regimes.

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