Category: 6823-69-4

Niu, Ziru; Pang, Ronald T. K.; Liu, Weimin; Li, Qian; Cheng, Ranran; Yeung, William S. B. published the artcile< Polymer-based precipitation preserves biological activities of extracellular vesicles from an endometrial cell line>, Computed Properties of 6823-69-4, the main research area is extracellular vesicle endometrial cell uterine luminal fluid; biol activity polymer based precipitation.

Extracellular vesicles (EVs) are membrane-bound vesicles released by cells and act as media for transfer of proteins, small RNAs and mRNAs to distant sites. They can be isolated by different methods. However, the biol. activities of the purified EVs have seldom been studied. In this study, we compared the use of ultracentrifugation (UC), ultra-filtration (UF), polymer-based precipitation (PBP), and PBP with size-based purification (PBP+SP) for isolation of EVs from human endometrial cells and mouse uterine luminal fluid (ULF). Electron microscopy revealed that the diameters of the isolated EVs were similar among the tested methods. UF recovered the highest number of EVs followed by PBP, while UC and PBP+SP were significantly less efficient (P<0.05). Based on the number of EVs-to-protein ratios, PBP had the least protein contamination, significantly better than the other methods (P<0.05). All the isolated EVs expressed exosome-enriched proteins CD63, TSG101 and HSP70. Incubation of the trophoblast JEG-3 cells with an equal amount of the fluorescence-labeled EVs isolated by the studied methods showed that many of the PBP-EVs treated cells were fluorescence pos. but only a few cells were labeled in the UC- and UF-EVs treated groups. Moreover, the PBP-EVs could transfer significantly more miRNA to the recipient cells than the other 3 methods (P<0.05). The PBP method could isolate EVs from mouse ULF; the diameter of the isolated EVs was 62 ± 19 nm and expressed CD63, TSG101 and HSP70 proteins. In conclusion, PBP could best preserve the activities of the isolated EVs among the 4 methods studied and was able to isolate EVs from a small volume of sample. The simple setup and low equipment demands makes PBP the most suitable method for rapid EV assessment and isolation of EVs in clin. and basic research settings. PLoS One published new progress about Blastocyst. 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

Kakiuchi, Yoshihiko; Kuroda, Shinji; Kanaya, Nobuhiko; Kumon, Kento; Tsumura, Tomoko; Hashimoto, Masashi; Yagi, Chiaki; Sugimoto, Ryoma; Hamada, Yuki; Kikuchi, Satoru; Nishizaki, Masahiko; Kagawa, Shunsuke; Tazawa, Hiroshi; Urata, Yasuo; Fujiwara, Toshiyoshi published the artcile< Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles>, Product Details of C30H30Cl2N6O2, the main research area is oncolytic adenovirotherapy tumor derived extracellular vesicle abscopal effect; abscopal effect; drug delivery system; exosome; extracellular vesicles; local treatment; oncolytic adenovirus; systemic delivery.

Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral s.c. HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs.

Molecular Therapy published new progress about Adenovirus E1A proteins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Product Details of C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Chen, Jinghua; Xu, Ruilian; Xia, Junxian; Huang, Jiacheng; Su, Binbin; Wang, Senming published the artcile< Aspirin inhibits hypoxia-mediated lung cancer cell stemness and exosome function>, COA of Formula: C30H30Cl2N6O2, the main research area is NSCLC aspirin hypoxia exosome HIF1 microRNA210 SOX2 cell proliferation; Aspirin; Exosomes; Hypoxia; Lung cancer; Stemness.

Epidemiol. studies have illustrated that regular aspirin consumption may decrease the risk of non-small cell lung cancer (NSCLC). The present study aims to investigate the mechanism of aspirin-induced inhibition of NSCLC development during hypoxia. A549 cells were pre-treated with the vehicle control or aspirin and then subjected to hypoxic culture. Cell viability was monitored by CCK-8 assay, and flow cytometry was performed to detect cell cycle distributions, apoptosis, and proportion of cancer stem cells (CSCs). Flow cytometric cell sorting was used to sep. CSCs. Quant. reverse transcription-polymerase chain reaction and Western blot were used to detect the mRNA and protein levels of stem cell markers and the related signaling mols. The abundance of prostaglandin E2 was detected by ELISA. Exosomes in the cell culture medium were isolated using ExoQuick, and the number of exosomes was quantified by the EXOCET exosome quantification assay kit. Cell migration and angiogenesis were monitored by transwell migration assay and in vitro angiogenesis experiments Aspirin inhibited cell proliferation and induced G2/M cell cycle arrest in hypoxic A549 cells; it also inhibited hypoxia-enhanced stemness in both A549 and ALDH+ cells. The drug reduced hypoxia-enhanced numbers of exosomes in A549 cells and exerted neg. effects on the hypoxia-mediated up-regulation of exosomal HIF-1α/COX-2 and expression of exosomal miR-135b and miR-210. While hypoxic-induced exosomes can promote the proliferation, migration, and angiogenesis of other A549 cells, aspirin can weaken this promotion by reducing the amount of exosome secreted and changing exosome contents. Aspirin inhibits the hypoxia-induced stemness, hypoxic-mediated exosome release, and malignant paracrine effects of A549 cells.

Pathology, Research and Practice published new progress about Angiogenesis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, COA of Formula: C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Huang, Yunlong; Li, Yuju; Zhang, Hainan; Zhao, Runze; Jing, Ran; Xu, Yinghua; He, Miao; Peer, Justin; Kim, Yeong C.; Luo, Jiangtao; Tong, Zenghan; Zheng, Jialin published the artcile< Zika virus propagation and release in human fetal astrocytes can be suppressed by neutral sphingomyelinase-2 inhibitor GW4869>, Computed Properties of 6823-69-4, the main research area is Zika virus infection astrocyte GW4869.

Zika virus (ZIKV) is a neurotrophic flavivirus that is capable of infecting humans, leading to brain abnormalities during fetal development. The ZIKV infectivity in neural target cells remains poorly understood. Here, we found that ZIKV specifically infected glial fibrillary acidic protein- and S100B-pos. primary human astrocytes derived from fetal brains. In contrast, neuron-specific Class III β-tubulin (TuJ1)-pos. neurons in the astrocyte cultures and SOX2-pos. neural progenitor cells derived from the fetal brains were less susceptible to ZIKV infection compared with astrocytes. The infected astrocytes released competent viral particles and manifested programmed cell death with a progressive cytopathic effect. Interestingly, ZIKV infection in human fetal astrocytes induced a significant increase of extracellular vesicles (EVs). Treatment with GW4869, a specific inhibitor of neutral sphingomyelinase-2, decreased EV levels, suppressed ZIKV propagation, and reduced the release of infectious virions in astrocytes. Therefore, ZIKV infects primary human fetal astrocytes and the infection can be suppressed by neutral sphingomyelinase-2 inhibitor GW4869. Further investigation into sphingomyelin metabolism and EVs may provide insights to the therapeutic treatment of ZIKV infection.

Cell Discovery published new progress about Antigens Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Yue, Kang-Yi; Zhang, Pei-Ran; Zheng, Min-Hua; Cao, Xiu-Li; Cao, Yuan; Zhang, Yi-Zhe; Zhang, Yu-Fei; Wu, Hai-Ning; Lu, Zhi-Hong; Liang, Liang; Jiang, Xiao-Fan; Han, Hua published the artcile< Neurons can upregulate Cav-1 to increase intake of endothelial cells-derived extracellular vesicles that attenuate apoptosis via miR-1290>, Synthetic Route of 6823-69-4, the main research area is caveolin apoptosis exosome microRNA human neuron.

Extracellular vesicles (EVs) including exosomes can serve as mediators of cell-cell communication under physiol. and pathol. conditions. However, cargo mols. carried by EVs to exert their functions, as well as mechanisms for their regulated release and intake, have been poorly understood. In this study, we examined the effects of endothelial cells-derived EVs on neurons suffering from oxygen-glucose deprivation (OGD), which mimics neuronal ischemia-reperfusion injury in human diseases. In a human umbilical endothelial cell (HUVEC)-neuron coculture assay, we found that HUVECs reduced apoptosis of neurons under OGD, and this effect was compromised by GW4869, a blocker of exosome release. Purified EVs could be internalized by neurons and alleviate neuronal apoptosis under OGD. A miRNA, miR-1290, was highly enriched in HUVECs-derived EVs and was responsible for EV-mediated neuronal protection under OGD. Interestingly, we found that OGD enhanced intake of EVs by neurons cultured in-vitro. We examined the expression of several potential receptors for EV intake and found that caveolin-1 (Cav-1) was upregulated in OGD-treated neurons and mice suffering from middle cerebral artery occlusion (MCAO). Knock-down of Cav-1 in neurons reduced EV intake, and canceled EV-mediated neuronal protection under OGD. HUVEC-derived EVs alleviated MCAO-induced neuronal apoptosis in-vivo. These findings suggested that ischemia likely upregulates Cav-1 expression in neurons to increase EV intake, which protects neurons by attenuating apoptosis via miR-1290.

Cell Death & Disease published new progress about Apoptosis. 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

Xu, Feng; Zhong, Jia-Yu; Lin, Xiao; Shan, Su-Kang; Guo, Bei; Zheng, Ming-Hui; Wang, Yi; Li, Fuxingzi; Cui, Rong-Rong; Wu, Feng; Zhou, En; Liao, Xiao-Bo; Liu, You-Shuo; Yuan, Ling-Qing published the artcile< Melatonin alleviates vascular calcification and ageing through exosomal miR-204/miR-211 cluster in a paracrine manner>, Category: imidazoles-derivatives, the main research area is melatonin vascular calcification ageing paracrine manner exosomal miR cluster; BMP2; ageing; exosomes; melatonin; miR-204/miR-211; vascular calcification.

In the elderly with atherosclerosis, hypertension and diabetes, vascular calcification and ageing are ubiquitous. Melatonin (MT) has been demonstrated to impact the cardiovascular system. In this study, we have shown that MT alleviates vascular calcification and ageing, and the underlying mechanism involved. We found that both osteogenic differentiation and senescence of vascular smooth muscle cells (VSMCs) were attenuated by MT in a MT membrane receptor-dependent manner. Moreover, exosomes isolated from VSMCs or calcifying vascular smooth muscle cells (CVSMCs) treated with MT could be uptaken by VSMCs and attenuated the osteogenic differentiation and senescence of VSMCs or CVSMCs, resp. Moreover, we used conditional medium from MT-treated VSMCs and Transwell assay to confirm exosomes secreted by MT-treated VSMCs attenuated the osteogenic differentiation and senescence of VSMCs through paracrine mechanism. We also found exosomal miR-204/miR-211 mediated the paracrine effect of exosomes secreted by VSMCs. A potential target of these two miRs was revealed to be BMP2. Furthermore, treatment of MT alleviated vascular calcification and ageing in 5/6-nephrectomy plus high-phosphate diet-treated (5/6 NTP) mice, while these effects were partially reversed by GW4869. Exosomes derived from MT-treated VSMCs were internalised into mouse artery detected by in vivo fluorescence image, and these exosomes reduced vascular calcification and ageing of 5/6 NTP mice, but both effects were largely abolished by inhibition of exosomal miR-204 or miR-211. In summary, our present study revealed that exosomes from MT-treated VSMCs could attenuate vascular calcification and ageing in a paracrine manner through an exosomal miR-204/miR-211.

Journal of Pineal Research published new progress about Aging, animal. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Murao, Atsushi; Tan, Chuyi; Jha, Alok; Wang, Ping; Aziz, Monowar published the artcile< Exosome-mediated eCIRP release from macrophages to induce inflammation in sepsis>, Application In Synthesis of 6823-69-4, the main research area is inflammation sepsis exosome extracellular cold inducible RNA binding protein; cytokines; eCIRP; exosomes; macrophage; neutrophil; sepsis.

Extracellular cold-inducible RNA-binding protein (eCIRP) is an important damage-associated mol. pattern (DAMP). Despite our understanding of the potentially harmful effects of eCIRP in sepsis, how eCIRP is released from cells remains elusive. Exosomes are endosome-derived extracellular vesicles, which carry proteins, lipids, and nucleic acids to facilitate intercellular communication and several extracellular functions. We hypothesized that eCIRP is released via exosomes to induce inflammation in sepsis. Exosomes isolated from the supernatants of LPS-treated macrophage culture and serum of endotoxemia and polymicrobial sepsis mice showed high purity, as revealed by their unique median sizes ranging between 70 and 126 nm in diameter eCIRP levels of the exosomes were significantly increased after LPS treatment in the supernatants of macrophage culture, mouse serum, and cecal ligation and puncture (CLP)-induced sepsis mouse serum. Protease protection assay demonstrated the majority of eCIRP was present on the surface of exosomes. Treatment of WT macrophages and mice with exosomes isolated from LPS-treated WT mice serum increased TNFα and IL-6 production However, treatment with CIRP-/- mice serum exosomes significantly decreased these levels compared with WT exosome-treated conditions. CIRP-/- mice serum exosomes significantly decreased neutrophil migration in vitro compared with WT exosomes. Treatment of mice with serum exosomes isolated from CIRP-/- mice significantly reduced neutrophil infiltration into the peritoneal cavity. Our data suggest that eCIRP can be released via exosomes to induce cytokine production and neutrophil migration. Thus, exosomal eCIRP could be a potential target to inhibit inflammation.

Frontiers in Pharmacology published new progress about Binding energy. 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

He, Zhonghan; Li, Yanfeng; Lian, Zhenwei; Liu, Jin; Xian, Hongyi; Jiang, Ran; Hu, Zuqing; Fang, Daokui; Hu, Dalin published the artcile< Exosomal secretion may be a self-protective mechanism of its source cells under environmental stress: A study on human bronchial epithelial cells treated with hydroquinone>, Product Details of C30H30Cl2N6O2, the main research area is bronchial epithelial cell line hydroquinone exosomal secretion environmental stress; DNA damage; exosomal secretion; human bronchial epithelial cells; hydroquinone; toxic effects.

Accumulating evidence reveals that exosome plays an important role in cell-to-cell communication in both physiol. and pathol. processes by transferring bioactive mols. However, the role of exosomal secretion in the adaptation of its source cells to the stimuli of environmental chems. remains elusive. In this study, we revealed that the exposure of hydroquinone (HQ; the main bioactive metabolite of benzene) to human bronchial epithelial cells (16HBE) resulted in decreased ability of cell proliferation and migration, and simultaneously DNA damage and micronuclei formation. Interestingly, when exosomal secretion of HQ treated 16HBE cells was inhibited with the inhibitor GW4869, cellular proliferation and migration were further significantly reduced; concurrently, their DNA damage and micronuclei formation were both further significantly aggravated. Herein, we conclude that exosomal secretion of 16HBE cells may be an important self-protective function against the toxic effects induced by HQ.

Journal of Applied Toxicology published new progress about Cell migration. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Product Details of C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Lin, Yi-Wei; Nhieu, Jennifer; Wei, Chin-Wen; Lin, Yu-Lung; Kagechika, Hiroyuki; Wei, Li-Na published the artcile< Regulation of exosome secretion by cellular retinoic acid binding protein 1 contributes to systemic anti-inflammation>, Electric Literature of 6823-69-4, the main research area is exosome secretion Crabp1 antiinflammation; Crabp1; Exosome; Inflammation; Macrophage; Neuron; RIP140; Retinoic acid.

Intercellular communications are important for maintaining normal physiol. processes. An important intercellular communication is mediated by the exchange of membrane-enclosed extracellular vesicles. Among various vesicles, exosomes can be detected in a wide variety of biol. systems, but the regulation and biol. implication of exosome secretion/uptake remains largely unclear. Cellular retinoic acid (RA) binding protein 1 (Crabp1) knockout (CKO) mice were used for in vivo studies. Extracellular exosomes were monitored in CKO mice and relevant cell cultures including embryonic stem cell (CJ7), macrophage (Raw 264.7) and hippocampal cell (HT22) using Western blot and flow cytometry. Receptor Interacting Protein 140 (RIP140) was depleted by Crispr/Cas9-mediated gene editing. Anti-inflammatory maker was analyzed using qRT-PCR. Clin. relevance was accessed by mining multiple clin. datasets. This study uncovers Crabp1 as a neg. regulator of exosome secretion from neurons. Specifically, RIP140, a pro-inflammatory regulator, can be transferred from neurons, via Crabp1-regulated exosome secretion, into macrophages to promote their inflammatory polarization. Consistently, CKO mice, defected in the neg. control of exosome secretion, have significantly elevated RIP140-containing exosomes in their blood and cerebrospinal fluid, and exhibit an increased vulnerability to systemic inflammation. Clin. relevance of this pathway is supported by patients data of multiple inflammatory diseases. Further, the action of Crabp1 in regulating exosome secretion involves its ligand and is mediated by its downstream target, the MAPK signaling pathway. Conclusions: This study presents the first evidence for the regulation of exosome secretion, which mediates intercellular communication, by RA-Crabp1 signaling. This novel mechanism can contribute to the control of systemic inflammation by transferring an inflammatory regulator, RIP140, between cells. This represents a new mechanism of vitamin A action that can modulate the homeostasis of system-wide innate immunity without involving gene regulation.

Cell Communication and Signaling published new progress about Animal cell (HT22). 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

Batista, Ines A.; Melo, Sonia A. published the artcile< Exosomes and the future of immunotherapy in pancreatic cancer>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is review exosome immunotherapy pancreatic ductal adenocarcinoma; exosomes; immunotherapy; pancreatic cancer.

A review. Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, associated with a late diagnosis and a five-year survival rate of 8%. Currently available treatments fall short in improving the survival and quality of life of PDAC patients. The only possible curative option is still the surgical resection of the tumor. Exosomes are extracellular vesicles secreted by cells that transport proteins, lipids, and nucleic acids to other cells, triggering phenotypic changes in the recipient cells. Tumor cells often secrete increased amounts of exosomes. Tumor exosomes are now accepted as important players in the remodeling of PDAC tumor stroma, particularly in the establishment of an immunosuppressive microenvironment. This has sparked the interest in their usefulness as mediators of immunomodulatory effects for the treatment of PDAC. In fact, exosomes are now under study to understand their potential as nanocarriers to stimulate an immune response against cancer. This review highlights the latest findings regarding the function of exosomes in tumor-driven immunomodulation, and the challenges and advantages associated with the use of these vesicles to potentiate immunotherapy in PDAC.

International Journal of Molecular Sciences published new progress about Drug bioavailability. 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