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#32272506   2020/04/09 To Up

Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS.

Berberine (BBR) is an isoquinoline alkaloid extracted from several commonly used Chinese herbs. Our previous studies demonstrated BBR-mediated alleviation of lung injury due to inflammation and decrease in the mortality of mice with influenza viral pneumonia. The recent argument of autophagy against inflammatory responses has aroused wide concerns. This study focuses on the reactive oxygen species-Nod-like receptor protein 3 (ROS-NLRP3) pathway to investigate whether BBR inhibits NLRP3 inflammasome activation by inducing mitophagy. Our results demonstrate that BBR and mitochondrion-targeted superoxide dismutase mimetic (Mito-TEMPO; a specific mitochondrial ROS scavenger) significantly restricted NLRP3 inflammasome activation, increased mitochondrial membrane potential (MMP), and decreased mitochondrial ROS (mtROS) generation in J774A.1 macrophages infected with PR8 influenza virus. These observations suggest that the inhibitory effects of BBR on NLRP3 inflammasome activation were associated with the amelioration of mtROS generation. BBR treatment induced regular mitophagy, as evident from the increase in microtubule-associated protein 1 light chain 3 II, decrease in p62, colocalization of LC3 and mitochondria, and formation of autophagosomes. However, 3-methyladenine, an autophagy inhibitor, reversed the inhibitory effects of BBR on mitochondrial damage and NLRP3 inflammasome activation in influenza virus-infected macrophages, indicating the involvement of mitophagy in mediating the inhibitory effects of BBR on NLRP3 inflammasome activation. Furthermore, the knockdown of Bcl-2/adenovirus E18-19-kDa interacting protein 3 (BNIP3) expression attenuated the effects of BBR on mitophagy induction to some extent, suggesting that the BBR-induced mitophagy may be, at least in part, mediated in a BNIP3-dependent manner. Similar results were obtained in vivo using a mouse model of influenza viral pneumonia that was administered with BBR. Taken together, these findings suggest that restricting NLRP3 inflammasome activation by decreasing ROS generation through mitophagy induction may be crucial for the BBR-mediated alleviation of influenza virus-induced inflammatory lesions.
Hui Liu, Leiming You, Jun Wu, Mengfan Zhao, Rui Guo, Haili Zhang, Rina Su, Qin Mao, Di Deng, Yu Hao

2605 related Products with: Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS.

1 mg100 101 mg25100 200 100 50 10 50 ug1 mL

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#32272497   2020/04/09 To Up

Unravelling the heterogeneity and dynamic relationships of tumor-infiltrating T cells by single-cell RNA sequencing analysis.

T cells are crucial for the success of immune-based cancer therapy. Reinvigorating antitumor T cell activity by blocking checkpoint inhibitory receptors has provided clinical benefits for many cancer patients. However, the efficacy of these treatments varies in cancer patients and the mechanisms underlying these diverse responses remain elusive. The density and status of tumor-infiltrating T cells have been shown to positively correlate with patient response to checkpoint blockades. Therefore, further understanding of the heterogeneity, clonal expansion, migration, and effector functions of tumor-infiltrating T cells will provide fundamental insights into antitumor immune responses. To this end, recent advances in single-cell RNA sequencing technology have enabled profound and extensive characterization of intratumoral immune cells and have improved our understanding of their dynamic relationships. Here, we summarize recent progress in single-cell RNA sequencing technology and current strategies to uncover heterogeneous tumor-infiltrating T cell subsets. In particular, we discuss how the coupling of deep transcriptome information with T cell receptor (TCR)-based lineage tracing has furthered our understanding of intratumoral T cell populations. We also discuss the functional implications of various T cell subsets in tumors and highlight the identification of novel T cell markers with therapeutic or prognostic potential.
Xin Yu, Lei Zhang, Ashutosh Chaudhry, Aaron S Rapaport, Wenjun Ouyang

2983 related Products with: Unravelling the heterogeneity and dynamic relationships of tumor-infiltrating T cells by single-cell RNA sequencing analysis.

100.00 ug1.00 flask100 extractions96 tests25 TESTS

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#32272493   2020/04/09 To Up

The Predictive Value of Early Changes in F-Fluoroestradiol Positron Emission Tomography/Computed Tomography During Fulvestrant 500 mg Therapy in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.

The aim of this study was to investigate the predictive value of early changes in F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) during fulvestrant 500 mg therapy in patients with estrogen receptor (ER)-positive metastatic breast cancer.
Min He, Cheng Liu, Qin Shi, Yuyun Sun, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Yingjian Zhang, Yin Liu, Guangyu Liu, Genhong Di, Zhongyi Yang, Zhonghua Wang, Zhiming Shao

1273 related Products with: The Predictive Value of Early Changes in F-Fluoroestradiol Positron Emission Tomography/Computed Tomography During Fulvestrant 500 mg Therapy in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.



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#32272449   2020/04/01 To Up

Transcriptomic responses to hypoxia in endometrial and decidual stromal cells.

Human reproductive success depends on a properly decidualized uterine endometrium that allows implantation and the formation of the placenta. At the core of the decidualization process are endometrial stromal fibroblasts (ESF) that differentiate to decidual stromal cells (DSC). As variations in oxygen levels are functionally relevant in endometrium both upon menstruation and during placentation, we assessed the transcriptomic responses to hypoxia in ESF and DSC. In both cell types hypoxia upregulated genes in classical hypoxia pathways such as glycolysis and the epithelial mesenchymal transition. In DSC hypoxia restored an ESF like transcriptional state for a subset of transcription factors that are known targets of the progesterone receptor, suggesting that hypoxia partially interferes with progesterone signaling. In both cell types hypoxia modified transcription of several inflammatory transcription factors that are known regulators of decidualization, including decreased transcription of STATs and increased transcription of CEBPs. We observed that hypoxia upregulated genes in ESF and DSC had a significant overlap with genes previously detected to be upregulated in endometriotic stromal cell. Promoter analysis of the genes in this overlap suggested the hypoxia upregulated Jun/Fos and CEBP transcription factors as potential drivers of endometriosis-associated transcription. Using immunohistochemistry we observed increased expression of JUND and CEBPD in endometriosis lesions compared to healthy endometria. Overall the findings suggest that hypoxic stress establishes distinct transcriptional states in ESF and DSC, and that hypoxia influences the expression of genes that contribute to the core gene regulation of endometriotic stromal cells.
Kalle T Rytkönen, Taija Heinosalo, Mehrad Mahmoudian, Xinghong Ma, Antti Perheentupa, Laura L Elo, Matti Poutanen, Gunter P Wagner

2469 related Products with: Transcriptomic responses to hypoxia in endometrial and decidual stromal cells.

96 wells100 µg1 kit10100 extractions100 1x10e7 cells100 96 assays

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#32272431   2020/04/06 To Up

Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways.

Postmenopausal osteoporosis results from estrogen withdrawal and is characterized mainly by bone resorption. Shikonin is a bioactive constitute of Chinese traditional herb which plays a role in antimicrobial and antitumor activities. The study was designed to investigate the role of shikonin on postmenopausal osteoporosis and explore its underlying mechanisms.
Kai Chen, Zijun Yan, Yiran Wang, Yilin Yang, Mengxi Cai, Chunyou Huang, Bo Li, Mingyuan Yang, Xiaoyi Zhou, Xianzhao Wei, Changwei Yang, Ziqiang Chen, Xiao Zhai, Ming Li

1705 related Products with: Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways.

400 ug100ug96T400 ug100 ul 100ul96 assays1 mg100 ul2ug1 mg50 ul

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#32272420   2020/03/26 To Up

Identification and development of non-cytotoxic cell death modulators: Impact of sartans and derivatives on PPARγ activation and on growth of imatinib-resistant chronic myelogenous leukemia cells.

4'-((2-Propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid derived from telmisartan was identified as lead for the design of cell death modulators. In this study, we evaluated the efficacy of telmisartan itself and other sartans in combination with imatinib against K562-resistant cells. The findings were directly used to further optimize the lead structure. Telmisartan and candesartan cilexetil represented the most effective sartans, thus the influence of carboxyl/methyl carboxylate groups at positions 7 (compounds 6, 7) or 4 (compounds 12-14) at the benzimidazole core was studied. Additionally, according to the results of a former structure-activity study, telmisartan was transformed to the related amide (1). Telmisartan amide 1, as well as the esters 6 and 12 markedly sensitized the resistant CML cells to imatinib treatment. Correlation with their potency to activate PPARγ is not given. Candesartan cilexetil, telmisartan and 1 showed the profile of partial agonists at PPARγ with EC values of 4.2, 4.3 and 9.1 μM, respectively, while 6 and 12 caused only marginal intrinsic activation at 10 μM (A = 22% and 13%). However, the repression of the STAT5 phosphorylation relates with the possibility to sensitize K562-resistant CML cells to imatinib treatment. It is worth mentioning that all compounds were per se non-cytotoxic at relevant concentrations.
Anna M Schoepf, Stefan Salcher, Petra Obexer, Ronald Gust

1142 related Products with: Identification and development of non-cytotoxic cell death modulators: Impact of sartans and derivatives on PPARγ activation and on growth of imatinib-resistant chronic myelogenous leukemia cells.

100ug10 mg1000 tests100ul1000 200ul25 mg1 ml100.00 ul10 mg10 mg

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#32272419   2020/03/06 To Up

Discovery of orally active indirubin-3'-oxime derivatives as potent type 1 FLT3 inhibitors for acute myeloid leukemia.

FMS-like receptor tyrosine kinase-3 (FLT3) is expressed on acute leukemia cells and is implicated in the survival, proliferation and differentiation of hematopoietic cells in most acute myeloid leukemia (AML) patients. Despite recent achievements in the development of FLT3-targeted small-molecule drugs, there are still unmet medical needs related to kinase selectivity and the progression of some mutant forms of FLT3. Herein, we describe the discovery of novel orally available type 1 FLT3 inhibitors from structure-activity relationship (SAR) studies for the optimization of indirubin derivatives with biological and pharmacokinetic profiles as potential therapeutic agents for AML. The SAR exploration provided important structural insights into the key substituents for potent inhibitory activities of FLT3 and in MV4-11 cells. The profile of the most optimized inhibitor (36) showed IC values of 0.87 and 0.32 nM against FLT3 and FLT3/D835Y, respectively, along with potent inhibition against MV4-11 and FLT3/D835Y expressed MOLM14 cells with a GI value of 1.0 and 1.87 nM, respectively. With the high oral bioavailability of 42.6%, compound 36 displayed significant in vivo antitumor activity by oral administration of 20 mg/kg once daily dosing schedule for 21 days in a mouse xenograft model. The molecular docking study of 36 in the homology model of the DFG-in conformation of FLT3 resulted in a reasonable binding mode in type 1 kinases similar to the reported type 1 FLT3 inhibitors Crenolanib and Gilteritinib.
Pyeonghwa Jeong, Yeongyu Moon, Je-Heon Lee, So-Deok Lee, Jiyeon Park, Jungeun Lee, Jiheon Kim, Hyo Jeong Lee, Na Yoon Kim, Jungil Choi, Jeong Doo Heo, Ji Eun Shin, Hyun Woo Park, Yoon-Gyoon Kim, Sun-Young Han, Yong-Chul Kim

2491 related Products with: Discovery of orally active indirubin-3'-oxime derivatives as potent type 1 FLT3 inhibitors for acute myeloid leukemia.

100Tests100ug Lyophilized100ug Lyophilized100 assays

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#32272418   2020/04/01 To Up

Neuronal ERK MAPK signaling in response to low-dose nanopolystyrene exposure by suppressing insulin peptide expression in Caenorhabditis elegans.

The responses of different organs are important for organisms against the toxicity of environmental toxicants. So far, the neuronal response to nanoplastic exposure and the underlying mechanisms are still largely unclear. Due to the sensitivity to environmental exposures, we here employed Caenorhabditis elegans as an animal model to examine the role of ERK MAPK signaling pathway in the neurons to regulate the response to nanopolystyrene (100 nm). Nanopolystyrene exposure in the range of μg/L could significantly increase expressions of genes (lin-45, mek-2, and mpk-1) encoding ERK MAPK signaling pathway. Nanopolystyrene at the predicted environmental concentration of 1 μg/L could only significantly increase the mpk-1 expression. Meanwhile, RNAi knockdown of any of these genes caused a susceptibility to nanopolystyrene toxicity. ERK/MPK-1 acted in the neurons to regulate the response to nanopolystyrene. Moreover, three genes (ins-4, ins-39, and daf-28) encoding insulin peptides were identified as the downstream targeted genes of neuronal mpk-1 in regulating the response to nanopolystyrene. In nanopolystyrene exposed nematodes, neuronal RNAi knockdown of ins-4, ins-39, or daf-28 decreased expression of intestinal daf-2 encoding insulin receptor and increased expression of intestinal daf-16 encoding FOXO transcriptional factor. Therefore, the neuronal ERK MAPK signaling responded to nanopolystyrene by modulating the insulin signaling-mediated communication between neurons and intestine in nematodes. Our findings are helpful for understanding the molecular basis of neuronal response to nanopolystyrene in organisms.
Man Qu, Dan Li, Yuexiu Qiu, Dayong Wang

1369 related Products with: Neuronal ERK MAPK signaling in response to low-dose nanopolystyrene exposure by suppressing insulin peptide expression in Caenorhabditis elegans.

2 Pieces/Box96 tests100 μg2 Pieces/Box96 assays100ug100ug1 Set100ug50 1 Set

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#32272397   2020/04/06 To Up

FCN-A mediates the inflammatory response and the macrophage polarization in Aspergillus fumigatus keratitis of mice by activating the MAPK signaling pathway.

Fungal keratitis (FK) is a severe corneal disease that may cause vision loss. Previous studies indicate that the innate immune response produces the most effective anti-Aspergillus immune resistance. Ficolin-A (FCN-A), a soluble pattern-recognition receptor (PRR) family plays an important role in the innate immunity. In this study, we aimed to study the role of FCN-A in the A. fumigatus infected cornea. Here for the first time, we reported that the expression of FCN-A increases after A. fumigatus infection in the cornea of mice. Then, our results showed that the down-regulation of FCN-A reduced the inflammatory response of the cornea infected mice and decreased the expression of the TNF-a, p-p38, p-JNK. We also found that FCN-A can affect the recruitment of macrophages in the cornea of mice with A. fumigatus keratitis. In the mouse model of A. fumigatus keratitis and the A. fumigatus stimulation of RAW 264.7 cells, knocking down of FCN-A expression promoted the macrophage polarization toward M2. Furthermore, we observed that both the p38 and JNK inhibitors pretreatment decreased the proportion of M1/M2 in RAW 264.7 cells. Taken together, our data provide evidence that FCN-A participated in the inflammatory response of A. fumigatus keratitis in mice. Moreover, FCN-A mediates the inflammatory response and the polarization of the macrophages by activating the MAPK signaling pathway in A. fumigatus keratitis.
Guoqiang Zhu, Guiqiu Zhao, Jing Lin, Cui Li, Qian Wang, Qiang Xu, Xudong Peng, Hengrui Zheng

2088 related Products with: FCN-A mediates the inflammatory response and the macrophage polarization in Aspergillus fumigatus keratitis of mice by activating the MAPK signaling pathway.

12 Pieces/Box2 Pieces/Box100.00 ul2 Pieces/Box

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#32272395   2020/04/06 To Up

4-hydroxybenzo[d]oxazol-2(3H)-one ameliorates LPS/D-GalN-induced acute liver injury by inhibiting TLR4/NF-κB and MAPK signaling pathways in mice.

The purpose of this study was to synthesize 4-hydroxybenzo[d]oxazol-2(3H)-one (HBO) and to investigate its protective effects on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury. HBO (CHON) was synthesized based on 2-nitro-resorcinol and identified by physicochemical analysis. In the animal experiment, mice were pretreated with HBO (50, 100, 200 mg/kg) for 10 days. At the end of pretreatment, the animals were injected with LPS (10 µg/kg)/D-GalN (700 mg/kg). The results showed that HBO significantly alleviated liver injury induced by LPS/D-GalN in mice. It remarkably decreased inflammatory response by reducing the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Moreover, HBO notably attenuated hepatocyte apoptosis by inhibiting the release of Cytochrome C (Cyt C) from mitochondria into the cytoplasm and regulating the expression of B-cell lymphoma-2 (Bcl-2) family. Furthermore, the result showed that HBO inhibited the expressions of nuclear factor kappa-B p50 (NF-κBp50), toll-like receptor 4 (TLR4), and myeloid differentiation factor 88 (MyD88), as well as the phosphorylation of inhibitor of nuclear factor kappa-B (IκB), inhibitor of nuclear factor kappa-B kinase-α/β (IKK-α/β), nuclear factor kappa-B p65 (NF-κBp65), suggesting that HBO had a certain influence on the TLR4/NF-κB pathway. In addition, the mitogen-activated protein kinase (MAPK) signaling pathway was also affected by HBO, as evidenced by the decrease in the phosphorylation levels of extracellular regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). In conclusion, our study suggested that HBO could protect against LPS/D-GalN-induced liver injury, moreover, treatment with HBO appeared to be capable of further regulating the TLR4/NF-κB and MAPK signaling pathways.
Hongyuan Wang, Xiugui Wei, Xian Wei, Xuemei Sun, Xiukun Huang, Yingqin Liang, Wanpeng Xu, Xunshuai Zhu, Xing Lin, Jun Lin

2946 related Products with: 4-hydroxybenzo[d]oxazol-2(3H)-one ameliorates LPS/D-GalN-induced acute liver injury by inhibiting TLR4/NF-κB and MAPK signaling pathways in mice.

2 Pieces/Box96T1 Set2 Pieces/Box1 Set10 mg1 Set1 Set11 inhibitors96 wells

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