Category: 6823-69-4

Qin, Xiaofeng; Lin, Xiaofang; Liu, Lang; Li, Ying; Li, Xiang; Deng, Zhenghao; Chen, Huiping; Chen, Hui; Niu, Zhiyuan; Li, Zisheng; Hu, Yongbin published the artcile< Macrophage-derived exosomes mediate silica-induced pulmonary fibrosis by activating fibroblast in an endoplasmic reticulum stress-dependent manner>, Related Products of 6823-69-4, the main research area is macrophage exosome proliferation migration pulmonary fibrosis endoplasmic reticulum stress; ER stress; exosomes; fibroblasts; macrophages; silicosis.

Macrophages play a key role in silicosis, and exosomes are potent mediators of intercellular communication. This suggests that macrophage-derived exosomes have a potential contribution to the pathogenesis of silicosis. To investigate whether macrophage-derived exosomes promote or inhibit lung fibrosis, in vitro, silica-exposed macrophage-derived exosomes (SiO2-Exos) were collected and cocultured with fibroblasts. The expression of collagen I and α-SMA was evaluated. Furthermore, the endoplasmic reticulum (ER) stress markers BIP, XBP1s and P-eIF2α were assessed after treatment with or without the ER stress inhibitor 4-PBA. In vivo, mice were pre-treated with the exosome secretion inhibitor GW4869 prior to silica exposure. After sacrifice, lung tissues were histol. examined, and the expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6) in bronchoalveolar lavage fluid (BALF) was measured. The results showed that the expression of collagen I and α-SMA was up-regulated after treatment with SiO2-Exos, accompanied by increased expression of BIP, XBP1s and P-eIF2α. Pre-treatment with 4-PBA reversed this effect. More importantly, an in vivo study demonstrated that pre-treatment with GW4869 decreased lung fibrosis and the expression of TNF-α, IL-1β and IL-6 in BALF. These results suggested that SiO2-Exos are profibrogenic and that the facilitating effect is dependent on ER stress.

Journal of Cellular and Molecular Medicine published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (ACTA2). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Related Products of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ratitong, Bridget; Marshall, Michaela; Pearlman, Eric published the artcile< Beta-Glucan-stimulated neutrophil secretion of IL-1α is independent of GSDMD and mediated through extracellular vesicles>, Related Products of 6823-69-4, the main research area is beta glucan interleukin neutrophil secretion extracellular vesicle; Dendritic cells; Exosomes; Extracellular vesicles; Gasdermin D; IL-1α; IL-1β; Macrophages; Neutrophils; Pyroptosis; β-glucan.

Neutrophils are an important source of interleukin (IL)-1β and other cytokines because they are recruited to sites of infection and inflammation in high numbers Although secretion of processed, bioactive IL-1β by neutrophils is dependent on NLRP3 and Gasdermin D (GSDMD), IL-1α secretion by neutrophils has not been reported. In this study, we demonstrate that neutrophils produce IL-1α following injection of Aspergillus fumigatus spores that express cell-surface β-glucan. Although IL-1α secretion by lipopolysaccharide (LPS)/ATP-activated macrophages and dendritic cells is GSDMD dependent, IL-1α secretion by β-glucan-stimulated neutrophils occurs independently of GSDMD. Instead, we found that bioactive IL-1α is in exosomes that were isolated from cell-free media of β-glucan-stimulated neutrophils. Further, the exosome inhibitor GW4869 significantly reduces IL-1α in extracellular vesicles (EVs) and total cell-free supernatant. Together, these findings identify neutrophils as a source of IL-1α and demonstrate a role for EVs, specifically exosomes, in neutrophil secretion of bioactive IL-1α.

Cell Reports published new progress about Animal gene, IL1A Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Related Products of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Peng, Lu; Wang, Yawen; Yang, Bingwei; Qin, Qi; Song, Erqun; Song, Yang published the artcile< Polychlorinated biphenyl quinone regulates MLKL phosphorylation that stimulates exosome biogenesis and secretion via a short negative feedback loop>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is polychlorinated biphenyl quinone MLKL protein phosphorylation exosome; Environmental pollution; Exosome; MLKL; Necroptosis; PCBs.

Polychlorinated biphenyls (PCBs) are one of the most refractory organic environmental pollutants that ubiquitous existence in nature. Due to the polymorphism of their metabolic pathway and corresponding downstream metabolites, PCBs’ toxicities are complicated and need extended investigation. In the present study, we discovered a novel regulatory mechanism of PCB quinone metabolite-driven programmed cell death (PCD), namely, necroptosis. We first confirmed that PCB quinone induces cancerous HeLa and MDA-MB-231 cells necroptosis via the phosphorylation of mixed lineage kinase domain-like MLKL (p-MLKL). Then, we found that PCB quinone-stimulated p-MLKL enhances exosome biogenesis and secretion. Exosome interacts with p-MLKL and releases p-MLKL to the outside of the cell, and ultimately alleviating PCB quinone-induced necroptosis. The inhibition of exosome secretion by GW4869 significantly elevated necroptotic level, indicating the establishment of a short neg. feedback loop of MLKL-exosome secretion upon PCB quinone challenge. Since exosome-mediated signaling showed great implications in various human diseases, this work may provide a new mechanism for PCBs-associated toxicity.

Environmental Pollution (Oxford, United Kingdom) published new progress about Disease, animal. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Matsuki-Fukushima, Miwako; Fujikawa, Kaoru; Inoue, Satoshi; Nakamura, Masanori published the artcile< Expression and localization of CD63 in the intracellular vesicles of odontoblasts>, SDS of cas: 6823-69-4, the main research area is expression intracellular vesicle odontoblast; CD63; Dentinogenesis; Odontoblast; Tooth development; Vesicle transport.

We hypothesized that odontoblasts release exosomes as well as dental pulp cells and focused on the exosome membrane marker CD63. Odontoblasts are well-differentiated mesenchymal cells that produce dentin. Dental pulp, a tissue complex formed with odontoblasts, releases exosomes to epithelial cells and stimulates their differentiation to ameloblasts. However, the localization of CD63 in differentiated odontoblasts is poorly understood. Therefore, herein, we aimed to reveal the expression of CD63 in odontoblasts during tooth development. We first investigated the localization of CD63 in mouse incisors and molars using immunofluorescence. In adult mouse incisors, the anti-CD63 antibody was pos. in mature odontoblasts and dental pulp cells but not in pre-odontoblasts along the ameloblasts in the apical bud. Addnl., the anti-CD63 antibody was observed as a vesicular shape in the apical area of odontoblast cytosol and inside Tomes’ fibers. The anti-CD63 antibody-pos. vesicles were also observed using immunoelectron microscopy. Moreover, during mouse mandibular molar tooth morphogenesis (E16 to postnatal 6 wk), labeling of anti-CD63 antibody was pos. in the odontoblasts at E18. In contrast, the anti-CD63 antibody was pos. in the dental pulp after postnatal day 10. Furthermore, anti-CD63 antibody was merged with the multivesicular body marker Rab7 in dental pulp tissues but not with the lysosome marker Lamp1. Finally, we determined the effect of a ceramide-generation inhibitor GW4869 on the mouse organ culture of tooth germ in vitro. After 28 days of GW4869 treatment, both CD63 and Rab7 were neg. in Tomes’ fibers, but were pos. in control odontoblasts. These results suggest that CD63-pos. vesicular organelles are important for mouse tooth morphogenesis.

Histochemistry and Cell Biology published new progress about Adult, mammalian. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, SDS of cas: 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Okuro, Renata Tiemi; Machado, Mariana Nascimento; Casquilho, Natalia Vasconcelos; Jardim-Neto, Alcendino; Roncally-Carvalho, Alysson; Atella, Georgia Correa; Zin, Walter Araujo published the artcile< The role of sphingolipid metabolism disruption on lipopolysaccharide-induced lung injury in mice>, Category: imidazoles-derivatives, the main research area is lung injury sphingolipid metabolism disruption; Ceramide; Enzyme inhibitors; Inflammation; Lipopolysaccharide; Lung injury; Sphingolipid.

This study assessed pulmonary outcomes generated by inhibiting key enzymes of sphingolipid metabolism pathways related to ceramide synthesis in a murine model of lung injury induced by lipopolysaccharide (LPS). C57BL/6 male adult mice received LPS intratracheally and the expressions of acid sphingomyelinase (ASM), neutral sphingomyelinase (NSM), serine palmitoyl transferase (SPT) and dihydroceramide synthase (DS) were assessed at 2, 4, 6, 12 and 24 h after LPS instillation in lung homogenate (n = 30). The pharmacol. inhibition of ASM, NSM, SPT and DS were assayed in other mice groups by three different doses of desipramine, GW4869, myriocin and fumonisin, resp. (n = 90). Their most EDs were administered i.p. 1 or 2 h before LPS to different animal groups (n = 120). Mice underwent determination of pulmonary mechanics, lung histopathol. aspects and apoptosis. The expression levels of the enzymes reached their peak at 2-4 h after LPS administration. ASM inhibition attenuated alveolar collapse and GW4869 decreased lung elastance, proinflammatory cytokines’ levels and was more effective to improve alveolar collapse than desipramine. On the other hand, SPT blockage aggravated lung lesion and no effects it was observed with fumonisin. Moreover, simultaneous administration of inhibitors (desipramine + GW4869, myriocin + fumonisin and all inhibitors together) resulted in no changes. Blockage of sphingomyelinases and the de novo pathways improved and aggravated lung injury, resp., putatively suggesting specific targets to therapeutic strategies in LPS-induced lung injury.

Pulmonary Pharmacology & Therapeutics published new progress about Alveolus. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Gao, Lingling; Nie, Xin; Gou, Rui; Hu, Yuexin; Dong, Hui; Li, Xiao; Lin, Bei published the artcile< Exosomal ANXA2 derived from ovarian cancer cells regulates epithelial-mesenchymal plasticity of human peritoneal mesothelial cells>, Quality Control of 6823-69-4, the main research area is ANXA ovarian cancer epithelial mesenchymal plasticity human peritoneal mesothelium; ANXA2; Implantation and metastasis; epithelial-mesenchymal plasticity; exosome; ovarian cancer.

Ovarian cancer, one of the malignant gynaecol. tumors with the highest mortality rate among female reproductive system, is prone to metastasis, recurrence and chemotherapy resistance, causing a poor prognosis. Exosomes can regulate the epithelial-mesenchymal plasticity of tumor cells, remodel surrounding tumor microenvironment, and affect tumor cell proliferation, invasion and metastasis. However, the function and mechanism of exosomes in the i.p. implantation of ovarian cancer remain unclear. In this study, exosomal annexin A2 (ANXA2) derived from ovarian cancer cells was co-cultured with human peritoneal mesothelial (HMrSV5) cells; functional experiments were conducted to explore the effects of exosomal ANXA2 on the biol. behavior of HMrSV5 and the related mechanisms. This study showed that ANXA2 in ovarian cancer cells can be transferred to HMrSV5 cells through exosomes, exosomal ANXA2 can not only promote the migration, invasion and apoptosis of HMrSV5 cells, but also regulates morphol. changes and fibrosis of HMrSV5 cells. Furthermore, ANXA2 promotes the mesothelial-mesenchymal transition (MMT) and degradation of the extracellular matrix of HMrSV5 cells through PI3K/AKT/mTOR pathway, finally affects pre-metastasis microenvironment of ovarian cancer, which provides a new theor. basis for the mechanism of i.p. implantation and metastasis of ovarian cancer.

Journal of Cellular and Molecular Medicine published new progress about Annexin A2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Quality Control of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Kavanagh, E. L.; Lindsay, S.; Halasz, M.; Gubbins, L. C.; Weiner-Gorzel, K.; Guang, M. H. Z.; McGoldrick, A.; Collins, E.; Henry, M.; Blanco-Fernandez, A.; Gorman, P. O.; Fitzpatrick, P.; Higgins, M. J.; Dowling, P.; McCann, A. published the artcile< Protein and chemotherapy profiling of extracellular vesicles harvested from therapeutic induced senescent triple negative breast cancer cells>, Related Products of 6823-69-4, the main research area is chemotherapy extracellular vesicle therapeutic induced senescent breast cancer.

Triple neg. breast cancer (TNBC) is an aggressive subtype with relatively poor clin. outcomes and limited treatment options. Chemotherapy, while killing cancer cells, can result in the generation of highly chemo resistant therapeutic induced senescent (TIS) cells that potentially form stem cell niches resulting in metastases. Intriguingly, senescent cells release significantly more extracellular vesicles (EVs) than non-senescent cells. Our aim was to profile EVs harvested from TIS TNBC cells compared with control cells to identify a potential mechanism by which TIS TNBC cells maintain survival in the face of chemotherapy. TIS was induced and confirmed in Cal51 TNBC cells using the chemotherapeutic paclitaxel (PTX) (Taxol). Mass spectrometry (MS) anal. of EVs harvested from TIS compared with control Cal51 cells was performed using Ingenuity Pathway Anal. and InnateDB programs. We demonstrate that TIS Cal51 cells treated with 75 nm PTX for 7 days became senescent (senescence-associated β-galactosidase (SA-β-Gal) pos., Ki67-neg., increased p21 and p16, G2/M cell cycle arrest) and released significantly more EVs (P = 0.0002) and exosomes (P = 0.0007) than non-senescent control cells. Moreover, TIS cells displayed an increased expression of the multidrug resistance protein 1/p-glycoprotein. MS anal. demonstrated that EVs derived from senescent Cal51 cells contained 142 proteins with a significant increased fold change compared with control EVs. Key proteins included ATPases, annexins, tubulins, integrins, Rabs and insoluble senescence-associated secretory phenotype (SASP) factors. A fluorescent analog of PTX (Flutax-2) allowed appreciation of the removal of chemotherapy in EVs from senescent cells. Treatment of TIS cells with the exosome biogenesis inhibitor GW4869 resulted in reduced SA-β-Gal staining (P = 0.04). In summary, this study demonstrates that TIS cells release significantly more EVs compared with control cells, containing chemotherapy and key proteins involved in cell proliferation, ATP depletion, apoptosis and the SASP. These findings may partially explain why cancer senescent cells remain viable despite chemo therapeutic challenge.

Oncogenesis published new progress about Annexins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Related Products of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Vora, Ashish; Zhou, Wenshuo; Londono-Renteria, Berlin; Woodson, Michael; Sherman, Michael B.; Colpitts, Tonya M.; Neelakanta, Girish; Sultana, Hameeda published the artcile< Arthropod EVs mediate dengue virus transmission through interaction with a tetraspanin domain containing glycoprotein Tsp29Fb>, Computed Properties of 6823-69-4, the main research area is Tsp29Fb E protein dengue virus transmission extracellular vesicle Aedes; HSP70; Tsp29Fb; arthropod EVs; dengue; transmission.

Dengue virus (DENV) is a mosquito-borne flavivirus that causes dengue fever in humans, worldwide. Using in vitro cell lines derived from Aedes albopictus and Aedes aegypti, the primary vectors of DENV, we report that DENV2/DENV3-infected cells secrete extracellular vesicles (EVs), including exosomes, containing infectious viral RNA and proteins. A full-length DENV2 genome, detected in arthropod EVs, was infectious to naive mosquito and mammalian cells, including human-skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed mosquito EVs with a size range from 30 to 250 nm. Treatments with RNase A, Triton X-100, and 4G2 antibody-bead binding assays showed that infectious DENV2-RNA and proteins are contained inside EVs. Viral plaque formation and dilution assays also showed securely contained infectious viral RNA and proteins in EVs are transmitted to human cells. Up-regulated HSP70 upon DENV2 infection showed no role in viral replication and transmission through EVs. In addition, qRT-PCR and immunoblotting results revealed that DENV2 up-regulates expression of a mosquito tetraspanin-domain-containing glycoprotein, designated as Tsp29Fb, in A. aegypti mosquitoes, cells, and EVs. RNAi-mediated silencing and antibody blocking of Tsp29Fb resulted in reduced DENV2 loads in both mosquito cells and EVs. Immunoprecipitation showed Tsp29Fb to directly interact with DENV2 E-protein. Furthermore, treatment with GW4869 (exosome-release inhibitor) affected viral burden, direct interaction of Tsp29Fb with E-protein and EV-mediated transmission of viral RNA and proteins to naive human cells. In summary, we report a very important finding on EV-mediated transmission of DENV2 from arthropod to mammalian cells through interactions with an arthropod EVs-enriched marker Tsp29Fb.

Proceedings of the National Academy of Sciences of the United States of America published new progress about Aedes aegypti. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Computed Properties of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Won, Jong Hoon; Kim, Seok Kyun; Shin, In Chul; Ha, Hae Chan; Jang, Ji Min; Back, Moon Jung; Kim, Dae Kyong published the artcile< Dopamine transporter trafficking is regulated by neutral sphingomyelinase 2/ceramide kinase>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is dopamine ceramide kinase SMase2 C1P CERK signaling cortex pheochromocytoma; Ceramide; Ceramide-1-phosphate; Dopamine transporter; Neutral sphingomyelinase 2; Sphingomyelin pathway; Trafficking.

Dopamine (DA) reuptake is the primary mechanism to terminate dopaminergic transmission in the synaptic cleft. The dopamine transporter (DAT) has an important role in the regulation of DA reuptake. This study provides anatomical and physiol. evidence that DAT recycling is regulated by ceramide kinase via the sphingomyelin pathway. First, the results show that DAT and neutral sphingomyelinase 2 (nSMase2) were successfully co-precipitated from striatal samples and were colocalized in the mouse striatum or PC12 cells. We also identified a protein-protein interaction between nSMase2 and DAT through in situ proximity ligation assay experiments in the mouse striatum. Second, dopamine (DA) stimulated the formation of ceramide and increased nSMase activity in PC12 cells, while treatment with a cell-permeable ceramide-1-phosphate (C1P) increased DA uptake. Third, we used inhibitors and siRNA to inhibit nSMase2 and ceramide kinase and observed the effects on DAT recycling in PC12 cells. Treatment with ceramide kinase inhibitor K1, or nSMase inhibitor GW4869, decreased DA uptake in PC12 cells, although the application of FB1, a ceramide synthase inhibitor, did not affect DA uptake. Transfection of nSMase2 and CERK siRNA decreased DAT surface level in PC12 cells. These results suggested that SM-derived C1P affects cell surface levels of DAT.

Cellular Signalling published new progress about Brain corpus striatum, dorsal striatum Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Li, Jianhua; Liu, Kuancheng; Liu, Yang; Xu, Yan; Zhang, Fei; Yang, Huijuan; Liu, Jiangxia; Pan, Tingting; Chen, Jieliang; Wu, Min; Zhou, Xiaohui; Yuan, Zhenghong published the artcile< Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity>, Application of C30H30Cl2N6O2, the main research area is IFN alpha induced antiviral activity exosome cell transmission.

The cell-to-cell transmission of viral resistance is a potential mechanism for amplifying the interferon-induced antiviral response. In this study, we report that interferon-α (IFN-α) induced the transfer of resistance to hepatitis B virus (HBV) from nonpermissive liver nonparenchymal cells (LNPCs) to permissive hepatocytes via exosomes. Exosomes from IFN-α-treated LNPCs were rich in mols. with antiviral activity. Moreover, exosomes from LNPCs were internalized by hepatocytes, which mediated the intercellular transfer of antiviral mols. Finally, we found that exosomes also contributed to the antiviral response of IFN-α to mouse hepatitis virus A59 and adenovirus in mice. Thus, we propose an antiviral mechanism of IFN-α activity that involves the induction and intercellular transfer of antiviral mols. via exosomes.

Nature Immunology published new progress about Adenoviridae. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Application of C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem