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Search results for: Anti-acetyl-Histone H3 (Ac-Lys9< SUP HXY[X][X

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#34562653   2021/09/20 To Up

Crystal structure of histone chaperone Vps75 from Candida albicans.

Vps75 is a histone chaperone that interacts with the fungal-specific histone acetyltransferase Rtt109 and stimulates its acetylation activity on histone H3. Here we report the crystal structure of Vps75 of Candida albicans, one of the most common fungal pathogens. CaVps75 exists as a headphone-like dimer that forms a large negatively charged region on its concave side, showing the potential to bind positively charged regions of histones. The distal ends of the concave side of the CaVps75 dimer are positively charged and each has one more α helix than yeast Vps75. CaVps75 exhibits ionic strength- and concentration-dependent higher oligomerization in solution. In the crystal, two dimers are bound through electrostatic interactions between charged regions on the concave side of their earmuff domains, and this inter-dimer interaction differs from the currently known inter-dimer interactions of Vps75s. Our results will help to understand the role of Vps75 in C. albicans.
Wenfeng Wang, Xi Chen, Zhongmei Yang, Xiaolei Chen, Changrun Li, Mingzhu Wang

1154 related Products with: Crystal structure of histone chaperone Vps75 from Candida albicans.

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#34562306   2021/09/25 To Up

Integrated analysis reveals distinct molecular, clinical, and immunological features of B7-H3 in acute myeloid leukemia.

The role of B7-H3 in acute myeloid leukemia (AML) is not fully understood. Two previous studies investigating its expression and significances in AML are partially different. In this study, we aimed to systematically characterize the genomic and immune landscape in AML patients with altered B7-H3 expression using multi-omics data in the public domain. We found significantly increased B7-H3 expression in AML compared to either other hematological malignancies or healthy controls. Clinically, high B7-H3 expression was associated with old age, TP53 mutations, wild-type WT1 and CEBPA, and the M3 and M5 FAB subtypes. Moreover, we observed that increased B7-H3 expression correlated significantly with a poor outcome of AML patients in four independent datasets. Gene set enrichment analysis (GSEA) revealed the enrichment of the "EMT" oncogenic gene signatures in high B7-H3 expressers. Further investigation suggested that B7-H3 was more likely to be associated with immune-suppressive cells (macrophages, neutrophils, dendritic cells, and Th17 cells). B7-H3 was also positively associated with a number of checkpoint genes, such as VISTA (B7-H5), CD80 (B7-1), CD86 (B7-2), and CD70. In summary, we uncovered distinct genomic and immunologic features associated with B7-H3 expression in AML. This may lead to a better understanding of the molecular mechanisms underlying B7-H3 dysregulation in AML and to the development of novel therapeutic strategies.
Ling-Yi Zhang, Ye Jin, Pei-Hui Xia, Jiang Lin, Ji-Chun Ma, Ting Li, Zi-Qi Liu, He-Lin Xiang, Chen Cheng, Zi-Jun Xu, Hong Zhou, Jun Qian

1793 related Products with: Integrated analysis reveals distinct molecular, clinical, and immunological features of B7-H3 in acute myeloid leukemia.

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#34562173   2021/09/25 To Up

Prognostic value of glutaminase 1 in breast cancer depends on H3K27me3 expression and menopausal status.

Glutaminase 1 (GLS) is a therapeutic target for breast cancer; although GLS inhibitors have been developed, only a few subjects responded well to the therapy. Considering that the expression of histone H3 lysine 27 trimethylation (H3K27me3) and menopausal status was closely linked to GLS, we examined the effects of H3K27me3 and menopausal status on GLS to breast cancer prognosis. Data for 962 women diagnosed with primary invasive breast cancer were analyzed. H3K27me3 and GLS expression in tumors were evaluated with tissue microarrays by immunohistochemistry. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival and progression-free survival were estimated using Cox regression models. Statistical interaction was assessed on multiplicative scale. There was a beneficial prognostic effect of GLS expression on overall survival for those with low H3K27me3 level (HR = 0.50, 95% CI: 0.20-1.28) but an adverse prognostic effect for those with high H3K27me3 level (HR = 3.90, 95% CI: 1.29-11.78) among premenopausal women, and the statistical interaction was significant (P = 0.003). Similar pattern was further observed for progression-free survival (HR = 0.44, 95% CI: 0.20-0.95 for low H3K27me3 level, HR = 1.35, 95% CI: 0.74-2.48 for high H3K27me3 level, P = 0.024). The statistical interaction did not occur among postmenopausal women. Our study showed that the prognostic effects of GLS on breast cancer correlated to the expression level of H3K27me3 and menopausal status, which would help optimize the medication strategies of GLS inhibitors.
Meng Zhou, Qian-Xin Chen, Yuan-Zhong Yang, Zhuo-Zhi Liang, Yue-Lin Li, Zi-Yi Huang, Zi-Jin Weng, Xiao-Fang Zhang, Jie-Xia Guan, Lu-Ying Tang, Ze-Fang Ren

1053 related Products with: Prognostic value of glutaminase 1 in breast cancer depends on H3K27me3 expression and menopausal status.

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#34561272   2021/09/24 To Up

TGFBI production by macrophages contributes to an immunosuppressive microenvironment in ovarian cancer.

The tumor microenvironment evolves during malignant progression with major changes in non-malignant cells, cytokine networks, and the extracellular matrix (ECM). In this study, we aimed to understand how the ECM changes during neoplastic transformation of serous tubal intraepithelial carcinoma lesions (STIC) into high-grade serous ovarian cancers (HGSOC). Analysis of the mechanical properties of human fallopian tubes (FT) and ovaries revealed that normal FT and fimbria had a lower tissue modulus, a measure of stiffness, than normal or diseased ovaries. Proteomic analysis of the matrisome fraction between FT, fimbria, and ovaries showed significant differences in the ECM protein transforming growth factor beta induced (TGFBI - also known as βig-h3). STIC lesions in the fimbria expressed high levels of TGFBI which was predominantly produced by CD163-positive macrophages proximal to STIC epithelial cells. In vitro stimulation of macrophages with TGFβ and IL4 induced secretion of TGFBI, whereas IFNɣ/LPS downregulated macrophage TGFBI expression. Immortalized FT secretory epithelial cells carrying clinically relevant TP53 mutations stimulated macrophages to secrete TGFBI and upregulated integrin αvβ3, a putative TGFBI receptor. Transcriptomic HGSOC datasets showed a significant correlation between TGFBI expression and alternatively activated macrophage signatures. Fibroblasts in HGSOC metastases expressed TGFBI and stimulated macrophage TGFBI production in vitro. Treatment of orthotopic mouse HGSOC tumors with an anti-TGFBI antibody reduced peritoneal tumor size, increased tumor monocytes, and activated β3-expressing unconventional T cells. In conclusion, TGFBI may favor an immunosuppressive microenvironment in STICs that persists in advanced HGSOC. Furthermore, TGFBI may be an effector of the tumor-promoting actions of TGFβ and a potential therapeutic target.
Laura Sm Lecker, Chiara Berlato, Eleni Maniati, Robin Delaine-Smith, Oliver M T Pearce, Owen Heath, Samuel J Nichols, Caterina Trevisan, Marian Novak, Jacqueline McDermott, James D Brenton, Pedro R Cutillas, Vinothini Rajeeve, Ana Hennino, Ronny Drapkin, Daniela Loessner, Frances R Balkwill

1329 related Products with: TGFBI production by macrophages contributes to an immunosuppressive microenvironment in ovarian cancer.

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#34560639   2021/09/24 To Up

Clinicoradiological characteristics of primary spinal cord H3 K27M-mutant diffuse midline glioma.

Primary spinal cord H3 K27M-mutant diffuse midline glioma (DMG) is a rare and devastating pathological entity. However, little attention has been paid to this disease. As a result, its clinicoradiological characteristics have yet to be described. The aim of this study was to describe the clinicoradiological characteristics of primary intramedullary H3 K27M-mutant DMG and to compare this tumor with the H3 K27 wild-type to explore potential features that could differentiate the two.
Lei Cheng, Leiming Wang, Qingyu Yao, Longbing Ma, Wanru Duan, Jian Guan, Can Zhang, Kai Wang, Zhenlei Liu, Xingwen Wang, Zuowei Wang, Hao Wu, Zan Chen, Fengzeng Jian

2331 related Products with: Clinicoradiological characteristics of primary spinal cord H3 K27M-mutant diffuse midline glioma.

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#34560263   2021/09/21 To Up

Development of BET inhibitors as potential treatments for cancer: A new carboline chemotype.

We describe our efforts to introduce structural diversity to a previously described triazole-containing N1-carboline series of bromodomain and extra-terminal (BET) inhibitors. N9 carbolines were designed to retain favorable binding interactions that the N1-carbolines possess. A convergent synthetic route enabled modifications to reduce clearance, enhance physicochemical properties, and improve the overall in vitro profile. This work led to the identification of a potent BET inhibitor, (S)-2-{8-fluoro-5-[(3-fluoropyridin-2-yl)(oxan-4-yl)methyl]-7-[4-(H)methyl-1-methyl-1H-1,2,3-triazol-5-yl]-5H-pyrido[3,2-b]indol-3-yl}propan-2-ol (10), a compound with enhanced oral exposure in mice. Subsequent evaluation in a mouse triple-negative breast cancer tumor model revealed efficacy at 4 mg/kg of N9-carboline 10.
Matthew D Hill, Claude Quesnelle, John Tokarski, Haiquan Fang, Carolynn Fanslau, Zuzana Haarhoff, Melissa Kramer, Shilpa Madari, Amy Wiebesiek, John Morrison, Jean Simmermacher-Mayer, Michael Sinz, Richard Westhouse, Chunshan Xie, Jiuqiao Zhao, Lisa Huang, Steven Sheriff, Chunhong Yan, Frank Marsilio, Gerry Everlof, Tatyana Zvyaga, Francis Lee, Ashvinikumar V Gavai, Andrew P Degnan

2996 related Products with: Development of BET inhibitors as potential treatments for cancer: A new carboline chemotype.

1,000 tests1 kit12100 assays400Tests100Tests100 assays100 plates1 kit100 tests

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#34560152   2021/09/21 To Up

Sophora subprostrate polysaccharide regulates histone acetylation to inhibit inflammation in PCV2-infected murine splenic lymphocytes in vitro and in vivo.

Porcine circovirus type 2 (PCV2) has caused large economic losses in the swine industry worldwide; therefore, research on relevant therapeutic medicines is still urgently needed. To define the relationship between histone acetylation and inflammation induced by PCV2, we investigated whether traditional Chinese medicinal polysaccharides could alleviate viral infection by regulating histone acetylation. In this study, Sophora subprostrate polysaccharide (SSP)-treated PCV2-infected murine splenic lymphocytes in vitro and murine spleen in vivo were used to explore the regulatory effects of SSP on inflammation and histone acetylation caused by PCV2. SSP at different concentrations significantly reduced the secretion levels of the proinflammatory cytokines TNF-α and IL-6, the activity of COX-2, the mRNA expression levels of TNF-α, IL-6, iNOS and COX-2 and the protein expression levels of iNOS and COX-2 but promoted the secretion and mRNA expression levels of IL-10. Furthermore, the different concentrations of SSP significantly regulated the activity of histone acetylase (HAT) and the mRNA expression of HAT1, increased the activity of histone deacetylase (HDAC) and the mRNA expression of HDAC1 and reduced the protein expression levels of Ac-H3 and Ac-H4. Overall, SSP inhibited inflammation in PCV2-infected murine splenic lymphocytes by regulating histone acetylation in vitro and in vivo, thus playing an important role in PCV2 infection.
Mi-Xia Cao, Jian Yang, Xin-Rui Wang, Wen-Yue Hu, Xiao-Dong Xie, Yi Zhao, Meng-Qian Liu, Ying-Yi Wei, Mei-Ling Yu, Ting-Jun Hu

1995 related Products with: Sophora subprostrate polysaccharide regulates histone acetylation to inhibit inflammation in PCV2-infected murine splenic lymphocytes in vitro and in vivo.

5mg48 assays 96 assays 5mg48 assays 10mg1mg96 assays 10mg10mg48 assays 50mg

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#34559286   2021/09/24 To Up

Effects of sirtuins on the riboflavin production in Ashbya gossypii.

This study focuses on sirtuins, which catalyze the reaction of NAD-dependent protein deacetylase, for riboflavin production in A. gossypii. Nicotinamide, a known inhibitor of sirtuin, made the color of A. gossypii colonies appear a deeper yellow at 5 mM. A. gossypii has 4 sirtuin genes (AgHST1, AgHST2, AgHST3, AgHST4) and these were disrupted to investigate the role of sirtuins in riboflavin production in A. gossypii. AgHST1∆, AgHST3∆, and AgHST4∆ strains were obtained, but AgHST2∆ was not. The AgHST1∆ and AgHST3∆ strains produced approximately 4.3- and 2.9-fold higher amounts of riboflavin than the WT strain. The AgHST3∆ strain showed a lower human sirtuin 6 (SIRT6)-like activity than the WT strain and only in the AgHST3∆ strain was a higher amount of acetylation of histone H3 K9 and K56 (H3K9ac and H3K56ac) observed compared to the WT strain. These results indicate that AgHst3 is SIRT6-like sirtuin in A. gossypii and the activity has an influence on the riboflavin production in A. gossypii. In the presence of 5 mM hydroxyurea and 50 µM camptothecin, which causes DNA damage, especially double-strand DNA breaks, the color of the WT strain colonies turned a deeper yellow. Additionally, hydroxyurea significantly led to the production of approximately 1.5 higher amounts of riboflavin and camptothecin also enhanced the riboflavin production even through the significant difference was not detected. Camptothecin tended to increase the amount of H3K56ac, but the amount of H3K56ac was not increased by hydroxyurea treatment. This study revealed that AgHst1 and AgHst3 are involved in the riboflavin production in A. gossypii through NAD metabolism and the acetylation of H3, respectively. This new finding is a step toward clarifying the role of sirtuins in riboflavin over-production by A. gossypii.Key points• Nicotinamide enhanced the riboflavin production in Ashbya gossypii.• Disruption of AgHST1 or AgHST3 gene also enhanced the riboflavin production in Ashbya gossypii.• Acetylation of H3K56 led to the enhancement of the riboflavin production in Ashbya gossypii.
Tatsuya Kato, Junya Azegami, Mai Kano, Hesham A El Enshasy, Enoch Y Park

1836 related Products with: Effects of sirtuins on the riboflavin production in Ashbya gossypii.

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#34557208   2021/09/07 To Up

The Role of Plant Origin Preparations and Phenological Stage in Anatomy Structure Changes in the Rhizogenesis of "Hurdal".

Most old roses are difficult to root when propagated by cuttings. This research focused on the response of stem cuttings of "Hurdal" to plant origin preparations used as rhizogenesis enhancers through changes to the anatomical structure of the basal part of the stem. Cuttings derived from shoots in four phenological stages were prepared for the experiment: flower buds closed (H1); fully flowering (H2); immediately after petals have fallen (H3); 7-14 days after petals have fallen (H4). The cuttings were treated with 0.4% indole butyric acid (IBA; Ukorzeniacz A) or 0.2% naphthalene acetic acid (NAA; Ukorzeniacz B), and with plant origin preparations: Algae extract (Bio Rhizotonic), Organic preparation (Root Juice), and Plant extract (Bio Roots). A high rooting percentage in comparison to the control (27.5%) was obtained after treatments of the H1 cuttings with Algae extract (90%), Organic preparation (80%), and Plant extract (75%). The H4 cuttings did not root, probably as a result of an overgrowing callus and limited xylem formation. The anatomical structure of the shoot differed in subsequent phenological stages during the period of rooting in various ways, depending on the rooting enhancer used for treatment. Numerous correlations between rooting percentage and anatomical structure were proved, including the key role of vascular bundles in increasing rooting percentage by widening the vessel diameter.
Marta Joanna Monder, Paweł Kozakiewicz, Agnieszka Jankowska

1151 related Products with: The Role of Plant Origin Preparations and Phenological Stage in Anatomy Structure Changes in the Rhizogenesis of "Hurdal".

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#34555253   2021/09/23 To Up

Association analysis of B7-H3 and B7-H4 gene single nucleotide polymorphisms in susceptibility to ankylosing spondylitis in eastern Chinese Han population.

This study was conducted to describe the association between the genetic variation of the recently identified immune checkpoint molecules B7-H3 and B7-H4, and the susceptibility to ankylosing spondylitis (AS). Two single nucleotide polymorphisms (SNPs) of B7-H3 gene and three SNPs of B7-H4 gene were genotyped in 649 AS patients and 646 age- and sex-matched healthy controls. Allele, genotype frequencies and different inheritance models were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and the demographic and clinical parameters of patients were recorded. Our data indicated that B7-H4 rs10801935 and rs3738414 polymorphisms were correlated with AS susceptibility. In the stratification analyses, the minor A allele and GA genotype of B7-H4 rs3738414 increased the risk of AS in male patients (OR = 1.244, 95%CI = 1.026-1.508; OR = 1.453, 95%CI = 1.120-1.886, respectively). However, the association did not reach statistical significance after Bonferroni correction. Furthermore, haplotype analysis revealed that B7-H4 haplotype block TAG was a risk factor for the onset of AS (OR = 1.190, 95%CI = 1.020-1.389). These findings suggested that B7-H4 gene polymorphism may contribute to AS susceptibility in eastern Chinese Han population.
Yuting Chen, Hui Yang, Shanshan Xu, Jiran Shen, Wei Xu, Ming Shao, Faming Pan

2830 related Products with: Association analysis of B7-H3 and B7-H4 gene single nucleotide polymorphisms in susceptibility to ankylosing spondylitis in eastern Chinese Han population.

101010100 5ug1 kit48 assays 1 ml100 10

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