Category: 6823-69-4

Huang, Limin; Hu, Chaoquan; Chao, Hui; Zhang, Yu; Li, Yong; Hou, Jing; Xu, Zhong; Lu, He; Li, Hong; Chen, Hui published the artcile< Drug-resistant endothelial cells facilitate progression, EMT and chemoresistance in nasopharyngeal carcinoma via exosomes>, Category: imidazoles-derivatives, the main research area is nasopharyngeal carcinoma endothelial cell EMT chemoresistance exosome; Drug resistance; Exosome; Human microvascular endothelial cells (HMECs); Nasopharyngeal carcinoma.

Recent antitumor drug development has included investigation of a wide variety of anti-angiogenesis therapies. Because cancer cells in tumors require new blood vessels to grow and spread, they stimulate capillary proliferation from existing vessels as well as new vessel formation from endothelial precursor cells. Our previous findings suggested that drug resistance in mouse endothelial cells supported tumor growth, but the relationship between endothelial cells (ECs) and nasopharyngeal carcinoma (NPC) cells remained unclear. Exosomes are small membrane vesicles that are released by several cell types, including human microvascular ECs (HMECs). Exosomes carrying membrane and cytoplasmic constituents have been described as participants in a novel mechanism of cell-to-cell communication. In the present study, we investigated the mechanisms underlying the interactions between HMECs and NPC cells. We found that drug-resistant HMECs secreted small heterogeneous 40-100 nm vesicles, defined as exosomes. Co-incubation of NPC cells with doxorubicin-resistant (R-DOX) HMEC-derived exosomes resulted in promotion of their proliferation, migration, and chemoresistance, as well as changes in the expression of epithelial-mesenchymal transition (EMT) markers. These effects were significantly inhibited by treatment with GW4869 (an exosome inhibitor). We also found that GW4869 inhibited the stimulation of drug-resistant HMECs on NPC progression by modulating EMT in vivo. These data suggest that exosomes participate in a novel mechanism by which drug-resistant ECs enhance NPC progression.

Cellular Signalling published new progress about Apoptosis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Matsumoto, Akihiro; Takahashi, Yuki; Nishikawa, Makiya; Sano, Kohei; Morishita, Masaki; Charoenviriyakul, Chonlada; Saji, Hideo; Takakura, Yoshinobu published the artcile< Accelerated growth of B16BL6 tumor in mice through efficient uptake of their own exosomes by B16BL6 cells>, SDS of cas: 6823-69-4, the main research area is mouse melanoma tumor cell growth exosome; Biodistribution; exosomes; melanoma; proliferation; uptake.

Exosomes are extracellular vesicles released by various cell types and play roles in cell-cell communication. Several studies indicate that cancer cell-derived exosomes play important pathophysiol. roles in tumor progression. Biodistribution of cancer cell-derived exosomes in tumor tissue is an important factor for determining their role in tumor proliferation; however, limited studies have assessed the biodistribution of exosomes in tumor tissues. In the present study, we examined the effect of cancer-cell derived exosomes on tumor growth by analyzing their biodistribution. Murine melanoma B16BL6-derived exosomes increased the proliferation and inhibited the apoptosis of B16BL6 cells, which was associated with an increase and decrease in the levels of proliferation- and apoptosis-related proteins, resp. GW4869-induced inhibition of exosome secretion decreased the proliferation of B16BL6 cells, and treatment of GW4869-treated cells with B16BL6-derived exosomes restored their proliferation. Next, we treated B16BL6 tumors in mice with B16BL6-derived exosomes and examined the biodistribution and cellular uptake of these exosomes. After the intratumoral injection of radiolabeled B16BL6-derived exosomes, most radioactivity was detected within the tumor tissues of mice. Fractionation of cells present in the tumor tissue showed that fluorescently labeled exosomes were mainly taken up by B16BL6 cells. Moreover, intratumoral injection of B16BL6-derived exosomes promoted tumor growth, whereas intratumoral injection of GW4869 suppressed tumor growth. These results indicate that B16BL6 cells secrete and take up their own exosomes to induce their proliferation and inhibit their apoptosis, which promotes tumor progression.

Cancer Science published new progress about Apoptosis. 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

Zhang, Lina; Jiang, Yuan; Deng, Songyun; Mo, Yunan; Huang, Yan; Li, Wenchao; Ge, Chenglong; Ren, Xinshu; Zhang, Haisong; Zhang, Xiaolei; Peng, Qianyi; Liu, Zhiyong; Huang, Li; Zhou, Fan; Ai, Yuhang published the artcile< S100B/RAGE/Ceramide signaling pathway is involved in sepsis-associated encephalopathy>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is human sepsis encephalopathy SB RAGE ceramide signaling pathway; Ceramide; Drp1; Mitochondrial dynamics; RAGE; S100B; Sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is one of the most common complications of sepsis, and it might lead to long-term cognitive dysfunction and disability. This study aimed to explore the role of S100 calcium binding protein B (S100B)/RAGE/ceramide signaling pathway in SAE. FPS-ZM1 (an inhibitor of RAGE), myriocin and GW4869 (an inhibitor of ceramide) were used to explore the role of S100B/RAGE/ceramide in acute brain injury and long-term cognitive impairment in sepsis. In addition, Mdivi-1 (inhibitor of Drp1) and Drp1 siRNA were utilized to assess the effects of C2-ceramide on neuronal mitochondria, and to explore the specific underlying mechanism in C2 ceramide-induced death of HT22 mouse hippocampal neuronal cells. Western blot anal. showed that sepsis significantly up-regulated S100B and RAGE. Nissl staining and Morris water maze (MWM) test revealed that inhibition of RAGE with FPS-ZM1 markedly attenuated cecal ligation and puncture (CLP)-induced brain damage and cognitive dysfunction. Furthermore, FPS-ZM1 relieved sepsis-induced C2-ceramide accumulation and abnormal mitochondrial dynamics. Moreover, inhibition of ceramide also showed similar protective effects both in vivo and in vitro. Furthermore, Mdivi-1 and Drp1 siRNA significantly reduced C2-ceramide-induced neuronal mitochondrial fragmentation and cell apoptosis in vitro. This study confirmed that S100B regulates mitochondrial dynamics through RAGE/ceramide pathway, in addition to the role of this pathway in acute brain injury and long-term cognitive impairment during sepsis.

Life Sciences published new progress about Advanced glycosylation end product receptors 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

Tavakoli Dargani, Zahra; Singla, Reetu; Johnson, Taylor; Kukreja, Rakesh; Singla, Dinender K. published the artcile< Exosomes derived from embryonic stem cells inhibit doxorubicin and inflammation-induced pyroptosis in muscle cells>, Synthetic Route of 6823-69-4, the main research area is muscle exosome embryonic stem cell doxorubicin inflammation pyroptosis; doxorubicin; doxorubicine; inflammation; muscle; pyroptose; pyroptosis.

Doxorubicin (Dox) is an effective anticancer drug. Unfortunately, it causes cardiac and muscle toxicity due to increased oxidative stress and inflammation; however, it remains unknown whether Dox induces “”pyroptosis”” – an inflammation-mediated cell death. We investigated whether Dox induces pyroptosis in mouse soleus muscle (Sol 8) cells in vitro and to show the protective effect of embryonic stem cell exosomes (ES-exos) on pyroptosis. Dox and inflammation-induced in vitro model was generated. Pyroptosis was confirmed using immunohistochem. (with putative markers caspase-1, IL-1β, and pro-inflammatory cytokine IL-18) and Western blotting of caspase-1 and IL-1β. The results show significant increase in the expression of caspase-1, IL-1β, and IL-18 following treatment with Dox, which was inhibited by ES-exos but not mouse embryonic fibroblast exosomes. Moreover, GW4869 compound inhibited functional activity of ES-exos, suggesting these vesicles are key players in the inhibition of pyroptosis. These results suggest that Dox induces inflammatory pyroptosis in Sol 8 cells, which is attenuated by ES-exos in vitro.

Canadian Journal of Physiology and Pharmacology published new progress about Embryonic fibroblast. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Synthetic Route of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Shi, Qin; Wang, Di; Ding, Xiaoying; Yang, Xiaoqing; Zhang, Yuquan published the artcile< Exosome-shuttled miR-7162-3p from human umbilical cord derived mesenchymal stem cells repair endometrial stromal cell injury by restricting APOL6>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is microRNA APOL exosome UCMSC endometrial stromal cell injury human; Endometrial injury; Exosome; Human umbilical cord mesenchymal stem cell; Repair; miR-7162-3p.

Recent studies have shown that exosomes (Exos) derived from stem cells can be used as paracrine factors to regenerate cells and tissues via shuttling miRNAs. Exos derived from human umbilical cord derived mesenchymal stem cells (UCMSCs) have been found to alleviate mifepristone-induced endometrial stromal cell (ESC) injury in vitro. Information on the functions and mechanisms of Exos from UCMSC-induced endometrial repair is limited and requires more study. UCMSC-Exos were isolated and identified by Transmission Electron Microscopy, Nanoparticle Tracking Anal. software, and western blot assays. The damaged-ESC model and the UCMSC co-culture system were established, while GW4869, a noncompetitive neutral sphingomyelinase (N-SMase) inhibitor, was used to investigate the effects of UCMSC-Exos on mifepristone-induced ESC injury. Cell apoptosis of damaged ESCs treated with UCMSCs was detected using the TUNEL assay and flow cytometry anal. Then, miRNA microarrays were performed to detect differentially expressed miRNA profiles in both UCMSCs and ESCs after coculturing. A subset of upregulated miRNAs was validated by qRT-PCR, and miRNA mimics/inhibitor were used to investigate the functions of miR-7162-3p. The miRNA-mRNA interactions were predicted by Targetscan software, while the miRNA binding sites were predicted by miRcode software. Moreover, dual-luciferase reporter, western blot assays and qPCR were conducted to identify the regulatory mechanisms between miR-7162- 3p and APOL6. UCMSCs attenuated mifepristone-induced endometrial stromal cell apoptosis by Exos, while three miRNAs (miR-6831-5p, miR-4669, and miR-7162-3p) were both upregulated in UCMSCs and ESCs after coculture, and were candidate effectors of UCMSC-Exos-mediated endometrial repair. We showed that miR7162-3p was shuttled by Exos from UCMSCs and regulated the expression of APOL6 by targeting its 3′-UTR in ESCs. These results showed UCMSC-Exos protected ESCs from mifepristone-induced apoptosis and played an active role in repairing the damaged ESCs by in vitro shuttling of miR-7162-3p. The miR-7162-3p overexpressed UCMSC-Exos may therefore be used in cell-free therapy of endometrial injury.

Archives of Biochemistry and Biophysics published new progress about 3′-Untranslated region 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

Ilnytska, Olga; Jeziorek, Maciej; Lai, Kimberly; Altan-Bonnet, Nihal; Dobrowolski, Radek; Storch, Judith published the artcile< Lysobisphosphatidic acid (LBPA) enrichment promotes cholesterol egress via exosomes in Niemann Pick type C1 deficient cells>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is NPC1 exosome cholesterol egress lysobisphosphatidic acid; Bis(monoacylglycero)phosphate; Cholesterol; Exosomes; Extracellular vesicles; Lysobisphosphatidic acid; Niemann-Pick C disease; Phosphatidylglycerol.

This article demonstrate that NPC1-independent cholesterol egress in PG/LBPA enriched cells occurs, at least in part, via increased exosomal secretion. We probed Western blots of exosome-enriched preparations from the culture supernatants of untreated and PG-treated human primary NPC1 fibroblasts (GM03123), and found that 24 h PG treatment increased the amount of three classical exosomal markers, Alix, Flotillin-1, and CD63, in the exosome fraction by approx. 2- to 5-fold in FBS-free medium. Immunofluorescent imaging of luminal LAMP1, a marker of the endo-lysosomal compartment, in non-permeabilized NPC1 mutant fibroblasts, revealed a 6 to 10-fold increase in LAMP1-pos. organelles near the cell surface at 3 and 6 h of PG incubation, suggesting their exocytosis at early time points after treatment. We also found that the amount of cholesterol is reduced in exosomes released from cells that were first pretreated with GW4869 for 12 h and then incubated with PG in the presence of GW4869 for an addnl. 24 h, relative to cells incubated with PG but not treated with the compound Increase in C18:1,22:6 LBPA species in PG-treated cells may contribute to the formation of ILV, leading to increased exosome secretion and, hence, increased cholesterol secretion. The author concluded that PG treatment of NPC1 deficient cells leads to a reduction in LE/LY cholesterol accumulation, at least in part via exosomal egress.

Biochimica et Biophysica Acta, Molecular and Cell Biology of Lipids published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (Alix). 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

Donate, Paula B.; de Lima, Kalil Alves; Peres, Raphael S.; Almeida, Fausto; Fukada, Sandra Y.; Silva, Tarcilia A.; Nascimento, Daniele C.; Cecilio, Nerry T.; Talbot, Jhimmy; Oliveira, Rene D.; Passos, Geraldo A.; Alves-Filho, Jose Carlos; Cunha, Thiago M.; Louzada-Junior, Paulo; Liew, Foo Y.; Cunha, Fernando Q. published the artcile< Cigarette smoke induces miR-132 in Th17 cells that enhance osteoclastogenesis in inflammatory arthritis>, Electric Literature of 6823-69-4, the main research area is rheumatoid arthritis osteoclastogenesis microRNA132 Th17 cell cigarette smoke; Th17; cigarette smoke; exosomes; osteoclastogenesis; rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction and severe morbidity. Cigarette smoking (CS) can exacerbate the incidence and severity of RA. Although Th17 cells and the Aryl hydrocarbon receptor (AhR) have been implicated, the mechanism by which CS induces RA development remains unclear. Here, using transcriptomic anal., we show that microRNA-132 is specifically induced in Th17 cells in the presence of either AhR agonist or CS-enriched medium. miRNA-132 thus induced is packaged into extracellular vesicles produced by Th17 and acts as a proinflammatory mediator increasing osteoclastogenesis through the down-regulation of COX2. In vivo, articular knockdown of miR-132 in murine arthritis models reduces the number of osteoclasts in the joints. Clin., RA patients express higher levels of miR-132 than do healthy individuals. This increase is further elevated by cigarette smoking. Together, these results reveal a hitherto unrecognized mechanism by which CS could exacerbate RA and further advance understanding of the impact of environmental factors on the pathogenesis of chronic inflammatory diseases.

Proceedings of the National Academy of Sciences of the United States of America published new progress about Argonaute proteins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (2). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Electric Literature of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Vuckovic, Slavica; Vandyke, Kate; Rickards, David A.; McCauley Winter, Padraig; Brown, Simon H. J.; Mitchell, Todd W.; Liu, Jun; Lu, Jun; Askenase, Philip W.; Yuriev, Elizabeth; Capuano, Ben; Ramsland, Paul A.; Hill, Geoffrey R.; Zannettino, Andrew C. W.; Hutchinson, Andrew T. published the artcile< The cationic small molecule GW4869 is cytotoxic to high phosphatidylserine-expressing myeloma cells>, Synthetic Route of 6823-69-4, the main research area is cationic small mol phosphatidylserine express myeloma cell; GW4869; multiple myeloma; phosphatidylserine; small molecule.

Summary : We have discovered that a small cationic mol., GW4869, is cytotoxic to a subset of myeloma cell lines and primary myeloma plasma cells. Biochem. anal. revealed that GW4869 binds to anionic phospholipids such as phosphatidylserine – a lipid normally confined to the intracellular side of the cell membrane. However, interestingly, phosphatidylserine was expressed on the surface of all myeloma cell lines tested (n = 12) and 9/15 primary myeloma samples. Notably, the level of phosphatidylserine expression correlated well with sensitivity to GW4869. Inhibition of cell surface phosphatidylserine exposure with brefeldin A resulted in resistance to GW4869. Finally, GW4869 was shown to delay the growth of phosphatidylserine-high myeloma cells in vivo. To the best of our knowledge, this is the first example of using a small mol. to target phosphatidylserine on malignant cells. This study may provide the rationale for the development of phosphatidylserine-targeting small mols. for the treatment of surface phosphatidylserine-expressing cancers.

British Journal of Haematology published new progress about Antitumor agents. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Synthetic Route of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Zhou, Huan; Li, Xuan; Yin, Yuan; He, Xiao-Tao; An, Ying; Tian, Bei-Min; Hong, Yong-Long; Wu, Li-An; Chen, Fa-Ming published the artcile< The proangiogenic effects of extracellular vesicles secreted by dental pulp stem cells derived from periodontally compromised teeth>, Application In Synthesis of 6823-69-4, the main research area is GW4869 pluripotent angiogenesis; Angiogenesis; Dental pulp stem cells; Extracellular vesicles; Inflammation; Periodontitis.

In this study, we investigated the proangiogenic effects of extracellular vesicles (EVs) secreted by P-DPSCs using in vitro and in vivo testing models. Patient-matched DPSCs derived from periodontally healthy teeth (H-DPSCs) were used as the control for P-DPSCs. Conditioned media (CMs) derived from H-DPSCs and P-DPSCs (H-CM and P-CM), CMs derived from both cell types pretreated with the EV secretion blocker GW4869 (H-GW and P-GW), and EVs secreted by H-DPSCs and P-DPSCs (H-EVs and P-EVs) were prepared to test their proangiogenic effects on endothelial cells (ECs). Cell proliferation, migration, and tube formation were assessed using the Cell Counting Kit-8 (CCK-8), transwell/scratch wound healing, and Matrigel assays, resp. Finally, a full-thickness skin defect model was applied to test the effects of EVs on wound healing and new vessel formation. Both H-CM and P-CM promoted EC angiogenesis, but the proangiogenic effects were compromised when ECs were incubated in H-GW and P-GW, wherein the EV secretion was blocked by pretreatment with GW4869. In EV-based incubations, although both H-EVs and P-EVs were found to enhance the angiogenesis-related activities of ECs, P-EVs exerted a more robust potential to stimulate EC proliferation, migration, and tube formation. The findings of the present study provide addnl. evidence that P-DPSCs derived from periodontally diseased teeth represent a potential source of cells for research and therapeutic use.

Stem Cell Research & Therapy published new progress about Angiogenesis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Application In Synthesis of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Zhang, Jing; Tao, Yu; Cai, Renfei; Wang, Yao published the artcile< The miR-196a-5p-rich extracellular vesicles from trophoblasts induce M1 polarization of macrophages in recurrent miscarriage>, Application In Synthesis of 6823-69-4, the main research area is recurrent miscarriage miR196a5p extracellular vesicle trophoblast macrophage polarization.

Numerous studies have described the presence of crosstalk between trophoblasts and macrophages and the critical role it plays in recurrent miscarriage (RM). However, the mechanism of trophoblast-derived extracellular vesicle (EV) miRNAs and their interactions with decidual macrophages in the pathogenesis of RM remains unclear. MiRNA-seq was used to identify the differentially expressed miRNAs between RM patients and healthy controls. qPCR and in situ hybridization assays were performed to analyze the expression levels of miR-196a-5p in RM. THP-1 cells were treated with EVs, and qPCR and flow cytometry were performed to explore the polarization of macrophages. To explore the crosstalk between trophoblasts and macrophages, a coculture model and a series of cell function assays were performed. We first demonstrated that miR-196a-5p expression was higher in the cytotrophoblasts of villous tissues and plasma EVs from RM patients. miR-196a-5p derived from trophoblasts could be transferred into macrophages via EVs to induce M1 polarization via IκBα-mediated NF-κB pathway. Moreover, we found that M1 macrophages induced by EV miR-196a-5p derived from trophoblasts conversely regulated the proliferation, migration, and apoptosis of trophoblasts via TNF-α. This study indicated that trophoblast-derived EV miR-196a-5p was pos. associated with RM and functioned by regulating the crosstalk between trophoblasts and macrophages. These findings may attribute to identify a novel biomarker specific for RM.

Journal of Immunology Research published new progress about Apoptosis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Application In Synthesis of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem