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#34551063   2021/09/22 To Up

Daratumumab for immune thrombotic thrombocytopenic purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy. It is caused by a severe ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, 13) deficiency due to circulating autoantibodies, and is associated with significant morbidity and mortality. Current treatment options include plasma exchange, immunosuppression, and caplacizumab. When remission is achieved, the risk of relapse is high, especially in patients with persistent ADAMTS13 deficiency. We report the eradication of persistent ADAMTS13 inhibitory autoantibodies and restoration of normal ADAMTS13 activity using the anti-CD38 antibody daratumumab in two patients with iTTP. One patient had a frequently relapsing course, and the other a treatment-refractory first episode. There were no relevant adverse drug reactions.
Jana Van den Berg, Johanna A Kremer Hovinga, Claudia Pfleger, Inga Hegemann, Gregor Thomas Stehle, Andreas Holbro, Jan-Dirk Studt

1560 related Products with: Daratumumab for immune thrombotic thrombocytopenic purpura.

50 ml100 tests100 ug 1 G 1L1.0 mg500 MG25 µg0.1 mg10 ml 500 ml

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#34546477   2021/09/21 To Up

Beneficial effects of secretome derived from mesenchymal stem cells with stigmasterol to negate IL-1β-induced inflammation in-vitro using rat chondrocytes-OA management.

Osteoarthritis (OA) is the most prevalent joint disease predominantly characterized by inflammation which drives cartilage destruction. Mesenchymal stem cells-condition medium (MSC-CM) or the secretome is enriched with bioactive factors and possesses anti-inflammatory and regenerative effects. The present study aimed at evaluating the effects of combining MSC-conditioned medium with stigmasterol compared with the individual treatments in alleviating interleukin-1 beta (IL-1β)-induced inflammation in rat chondrocytes. Stigmasterol is a phytosterol exhibiting anti-inflammatory effects. IL-1β (10 ng/ml) was used to induce inflammation and mimic OA in-vitro in primary rat articular chondrocytes. The IL-1β-stimulated chondrocytes were treated with MSC-CM, stigmasterol, and a combination of MSC-CM and stigmasterol for 24 h. Cell viability was measured using MTT assay. Protein expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), collagen II (COL2A1) and matrix metalloproteinase (MMP)-13 were evaluated by immunofluorescence. Gene expression levels of MMP-3, MMP-13 and A Disintegrin-like and Metalloproteinases with Thrombospondin Motifs (ADAMTS)-5 were measured using qRT-PCR. NF-κB signaling pathway was studied using western blotting. A significant reduction in the expression of iNOS, IL-6, MMP-3, MMP-13 and ADAMTS-5, and a significant increase in COL2A1 expression was observed in the rat chondrocytes across all the treatment groups. However, the combination treatment of MSC-CM and stigmasterol remarkably reversed the IL-1β-induced pro-inflammatory/pro-catabolic responses to near normal levels comparable to the control group. The combination treatment (MSC-CM + stigmasterol) elicited a superior anti-inflammatory/anti-catabolic effect by inhibiting the IL-1β-induced NF-κB activation evidenced by the negligible phosphorylation of p65 and IκBα subunits, thereby emphasizing the benefit of the combination therapy over the individual treatments.
Samuel Joshua Pragasam Sampath, Subha Narayan Rath, Nagasuryaprasad Kotikalapudi, Vijayalakshmi Venkatesan

2165 related Products with: Beneficial effects of secretome derived from mesenchymal stem cells with stigmasterol to negate IL-1β-induced inflammation in-vitro using rat chondrocytes-OA management.

5 x 10A5 cells/vial24 wells1 kit(96 Wells)11 vial1 x 10^6 cells/vial1 mg10 ug1.00 flask24 wells1 kit(96 Wells)1 ml

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#34528498   // To Up

Overexpression of ADAM9 decreases radiosensitivity of hepatocellular carcinoma cell by activating autophagy.

A disintegrin and a metalloprotease (ADAM)9 upregulated within human hepatocellular carcinoma (HCC) cells, but its effect on HCC radiosensitivity remains unknown. The present work aimed to examine the effect of ADAM9 on HCC radiosensitivity and to reveal its possible mechanism, which may be helpful in identifying a potential therapeutic strategy. Changes in ADAM9 expression after X-ray irradiation were identified using western blot, qRT-PCR, and immunofluorescence. ADAM9 stable knockdown and overexpression cell lines were constructed using lentivirus packaging. The radiosensitivity of HCC cells with altered ADAM9 expression was examined by CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays. This study also determined how autophagy affected HCC cell radiosensitivity. Furthermore, ADAM9, p62 and Bax expressions in HCC tissues that were removed after radiotherapy were detected by immunohistochemistry, and the relationship among the levels of these molecules was statistically analyzed. The level of ADAM9expression in HCC cells increased after X-ray irradiation. Through CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays, this work discovered the increased MHCC97H cell radiosensitivity after ADAM9 knockdown, and the radiosensitivity of Huh7 cells decreased after the overexpression of ADAM9. Furthermore, ADAM9 induced HCC cell autophagy via downregulating Nrf2 expression, while autophagy inhibition or induction reversed the effects of altered ADAM9 expression on radiosensitivity. Moreover, ADAM9 level showed a negative correlation with Bax and p62 expression within HCC tissues after radiotherapy. Taken together, ADAM9 decreased the radiosensitivity of HCC cells, and autophagy mediated this process.
Lijin Zhu, Yuanyuan Zhao, Li Yu, Xinjia He, Yingju Wang, Peng Jiang, Rong Yu, Wei Li, Bin Dong, Xiang Wang, Yinying Dong

1794 related Products with: Overexpression of ADAM9 decreases radiosensitivity of hepatocellular carcinoma cell by activating autophagy.

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#34527702   2021/08/30 To Up

Extracellular Matrix Enzymes and Immune Cell Biology.

Remodelling of the extracellular matrix (ECM) by ECM metalloproteinases is increasingly being associated with regulation of immune cell function. ECM metalloproteinases, including Matrix Metalloproteinases (MMPs), A Disintegrin and Metalloproteinases (ADAMs) and ADAMs with Thombospondin-1 motifs (ADAMTS) play a vital role in pathogen defence and have been shown to influence migration of immune cells. This review provides a current summary of the role of ECM enzymes in immune cell migration and function and discusses opportunities and limitations for development of diagnostic and therapeutic strategies targeting metalloproteinase expression and activity in the context of infectious disease.
Meagan McMahon, Siying Ye, Jess Pedrina, Daniel Dlugolenski, John Stambas

2661 related Products with: Extracellular Matrix Enzymes and Immune Cell Biology.

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#34527101   2021/08/25 To Up

Infection as Trigger for Congenital Thrombotic Thrombocytopenic Purpura in an Adult Patient.

Congenital thrombotic thrombocytopenic purpura (cTTP) is an inherited disease that is sometimes fatal in early childhood. cTTP is similar to idiopathic thrombotic thrombocytopenic purpura (iTTP); both are characterized by varying levels of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and end-organ damage secondary to occlusion of the microvasculature. cTTP is caused by a partial or total deficiency or loss of function of ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). We report the case of a 33-year-old woman who was mistakenly diagnosed with primary immune thrombocytopenia (ITP) during childhood. The patient was referred to our center with dyspnea, fatigue, fever, and jaundice with no clinical bleeding. Laboratory features were compatible with MAHA; ADAMTS-13 activity was at 0%, with negativity for ADAMTS-13 antibodies. We concluded the final diagnosis was cTTP. The triggering factor identified for MAHA was a double infection: central venous catheter bacterial infection and atypical pneumonia. After 7 days of treatment with antibiotics and ongoing total plasma exchange (TPE), the patient responded favorably. Our patient received fresh frozen plasma (FFP) infusion once every 2 weeks, and prophylactic voriconazole remained under control at the time of writing. As demonstrated in this case, effective treatment of the trigger cause helps reduce the need for continuous FFP exposure and controls the MAHA.
Diego Alberto Lozano Jaramillo, Marco Alejandro Jimenez Ochoa

1364 related Products with: Infection as Trigger for Congenital Thrombotic Thrombocytopenic Purpura in an Adult Patient.

48 samples100 μg50 assays900 tests0.1ml (1mg/ml)100 μg100 μg96 tests100 μg96 Tests100 μg100 μg

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#34526403   // To Up

Posttranslational modifications by ADAM10 shape myeloid antigen-presenting cell homeostasis in the splenic marginal zone.

The spleen contains phenotypically and functionally distinct conventional dendritic cell (cDC) subpopulations, termed cDC1 and cDC2, which each can be divided into several smaller and less well-characterized subsets. Despite advances in understanding the complexity of cDC ontogeny by transcriptional programming, the significance of posttranslational modifications in controlling tissue-specific cDC subset immunobiology remains elusive. Here, we identified the cell-surface-expressed A-disintegrin-and-metalloproteinase 10 (ADAM10) as an essential regulator of cDC1 and cDC2 homeostasis in the splenic marginal zone (MZ). Mice with a CD11c-specific deletion of ADAM10 (ADAM10) exhibited a complete loss of splenic ESAM cDC2A because ADAM10 regulated the commitment, differentiation, and survival of these cells. The major pathways controlled by ADAM10 in ESAM cDC2A are Notch, signaling pathways involved in cell proliferation and survival (e.g., mTOR, PI3K/AKT, and EIF2 signaling), and EBI2-mediated localization within the MZ. In addition, we discovered that ADAM10 is a molecular switch regulating cDC2 subset heterogeneity in the spleen, as the disappearance of ESAM cDC2A in ADAM10 mice was compensated for by the emergence of a Clec12a cDC2B subset closely resembling cDC2 generally found in peripheral lymph nodes. Moreover, in ADAM10 mice, terminal differentiation of cDC1 was abrogated, resulting in severely reduced splenic Langerin cDC1 numbers. Next to the disturbed splenic cDC compartment, ADAM10 deficiency on CD11c cells led to an increase in marginal metallophilic macrophage (MMM) numbers. In conclusion, our data identify ADAM10 as a molecular hub on both cDC and MMM regulating their transcriptional programming, turnover, homeostasis, and ability to shape the anatomical niche of the MZ.
Nathalie Diener, Jean-Fred Fontaine, Matthias Klein, Thomas Hieronymus, Florian Wanke, Florian C Kurschus, Andreas Ludwig, Carl Ware, Paul Saftig, Tobias Bopp, Björn E Clausen, Ronald A Backer

2652 related Products with: Posttranslational modifications by ADAM10 shape myeloid antigen-presenting cell homeostasis in the splenic marginal zone.

0.1ml (1mg/ml)0.1ml (1mg/ml)1x10e7 cells1.00 flask100ug Lyophilized50ul100ug Lyophilized2 ml2 Pieces/Box

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#34523355   2021/09/15 To Up

ADAM10 Partially Protects Mice against Influenza Pneumonia by Suppressing Specific Myeloid Cell Population.

The influenza virus infection poses a serious health threat worldwide. Myeloid cells play pivotal roles in regulating innate and adaptive immune defense. A disintegrin and metalloproteinase (ADAM) family of proteins contribute to various immune responses; however, the role of ADAM10 in influenza virus infection remains largely unknown. Herein, we investigated its role, focusing on myeloid cells, during influenza virus infection in mice. Adam10/Lyz2-Cre (Adam10) and control Adam10 mice were intranasally infected with 200 plaque-forming units of influenza virus A/H1N1/PR8/34. Adam10 mice exhibited a significantly higher mortality rate, stronger lung inflammation, and a higher virus titer in the lungs than control mice. Macrophages and inflammatory cytokines such as TNF-α, IL-1b, and CCL2 were increased in bronchoalveolar lavage fluid from Adam10 mice following infection. CD11bLy6GF4/80 myeloid cells, which had an inflammatory monocytes/macrophages-like phenotype, were significantly increased in the lungs of Adam10 mice. Adoptive transfer experiments suggested that these cells likely contributed to the poorer prognosis in Adam10 mice. Seven days after infection, CD11bLy6GF4/80 lung cells exhibited significantly higher arginase-1 expression levels in Adam10 mice than in control mice, while an arginase-1 inhibitor improved the prognosis of Adam10 mice. Enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF)/GM-CSF receptor signaling likely contributed to this process. Collectively, these results indicate that myeloid ADAM10 protects against influenza virus pneumonia and may be a promising therapeutic target.
Satoshi Okamori, Makoto Ishii, Takanori Asakura, Shoji Suzuki, Ho Namkoong, Shizuko Kagawa, Ahmed E Hegab, Kazuma Yagi, Hirofumi Kamata, Tatsuya Kusumoto, Takunori Ogawa, Hayato Takahashi, Masaki Yoda, Keisuke Horiuchi, Naoki Hasegawa, Koichi Fukunaga

2454 related Products with: ADAM10 Partially Protects Mice against Influenza Pneumonia by Suppressing Specific Myeloid Cell Population.

2 Pieces/Box1mg2 Pieces/Box2 Pieces/Box100.00 ug100ug2 Pieces/Box100.00 ug100ug1mg

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#34522779   2021/08/27 To Up

Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage.

The present research was designed to examine the effects of disintegrin metalloproteinases 10 (ADAM10) on the doxorubicin (DOX)-induced dilated cardiomyopathy (DCM) and the mechanisms involved, with a focus on ADAM10-dependent cleavage of N-cadherin. The present study constructed recombinant lentiviral vectors expressing short hairpin RNA (shRNA) targeting the ADAM10 gene. H9C2 cells were treated with the recombinant lentivirus or GI254023 (an ADAM10 inhibitor). The expression level of N-cadherin and its C-terminal fragment1 (CTF1) was tested by western blotting and flow cytometry. The adhesion ability was analyzed using a plate adhesion model. Cardiac function and morphology were assessed in control and lentivirus-transfected rats with or without DOX treatment. The inhibition of ADAM10 activity significantly increased the expression of full-length N-cadherin on the cellular surface and reduced CTF1 generation and . The adhesion ability was also increased in ADAM10-knockdown H9C2 cells. Furthermore, DOX-induced myocardial dysfunction was ameliorated in rats transfected with ADAM10-shRNA lentivirus. These findings demonstrated that ADAM10 specifically cleaves N-cadherin in cardiomyocytes. ADAM10-induced N-cadherin cleavage results in changes in the adhesive behavior of cells. Therefore, ADAM10 may serve as a therapeutic target to reverse cardiac remodeling in DCM.
Xiaoou Li, Feng Pan, Bing He, Chengzhi Fang

2207 related Products with: Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage.

1 mg1.00 flask100 µg 1 kit(s) 0.05 mgOne 96-Well Strip Micropl100ug Lyophilized2100 ug 5 G100ug Lyophilized2

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#34522714   2020/11/21 To Up

Sulfuretin exerts diversified functions in the processing of amyloid precursor protein.

Sulfuretin is a flavonoid that protects cell from damage induced by reactive oxygen species and inflammation. In this study, we investigated the role of sulfuretin in the processing of amyloid precursor protein (APP), in association with the two catalytic enzymes the α-secretase a disintegrin and metalloproteinase (ADAM10), and the beta-site APP cleaving enzyme 1 (BACE1) that play important roles in the generation of β amyloid protein (Aβ) in Alzheimer's disease (AD). We found that sulfuretin increased the levels of the immature but not the mature form of ADAM10 protein. The enhanced ADAM10 transcription by sulfuretin was mediated by the nucleotides -444 to -300 in the promoter region, and was attenuated by silencing or mutation of transcription factor retinoid X receptor (RXR) and by GW6471, a specific inhibitor of peroxisome proliferator-activated receptor α (PPAR-α). We further found that sulfuretin preferentially increased protein levels of the immature form of APP (im-APP) but significantly reduced those of BACE1, sAPPβ and β-CTF, whereas Aβ1-42 levels were slightly increased. Finally, the effect of sulfuretin on BACE1 and im-APP was selectively attenuated by the translation inhibitor cycloheximide and by lysosomal inhibitor chloroquine, respectively. Taken together, (1) RXR/PPAR-α signaling was involved in sulfuretin-mediated ADAM10 transcription. (2) Alteration of Aβ protein level by sulfuretin was not consistent with that of ADAM10 and BACE1 protein levels, but was consistent with the elevated level of im-APP protein, suggesting that im-APP, an isoform mainly localized to trans-Golgi network, plays an important role in Aβ generation.
Jian Chen, Biao Luo, Bi-Rou Zhong, Kun-Yi Li, Qi-Xin Wen, Li Song, Xiao-Jiao Xiang, Gui-Feng Zhou, Li-Tian Hu, Xiao-Juan Deng, Yuan-Lin Ma, Guo-Jun Chen

2550 related Products with: Sulfuretin exerts diversified functions in the processing of amyloid precursor protein.

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