Category: 6823-69-4

Young, Simon A.; Smith, Terry K. published the artcile< The essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei>, Synthetic Route of 6823-69-4, the main research area is neutral sphingomyelinase trafficking variant surface glycoprotein Trypanosoma drug target.

Sphingomyelin is the main sphingolipid in Trypanosoma brucei, the causative agent of African sleeping sickness. In vitro and in vivo characterization of the T. brucei neutral sphingomyelinase demonstrates that it is directly involved in sphingomyelin catabolism. Gene knockout studies in the bloodstream form of the parasite indicate that the neutral sphingomyelinase is essential for growth and survival, thus highlighting that the de novo biosynthesis of ceramide is unable to compensate for the loss of sphingomyelin catabolism. The phenotype of the conditional knockout has given new insights into the highly active endocytic and exocytic pathways in the bloodstream form of T. brucei. Hence, the formation of ceramide in the endoplasmic reticulum affects post-Golgi sorting and rate of deposition of newly synthesized GPI-anchored variant surface glycoprotein on the cell surface. This directly influences the corresponding rate of endocytosis, via the recycling endosomes, of pre-existing cell surface variant surface glycoprotein. The trypanosomes use this coupled endocytic and exocytic mechanism to maintain the cell d. of its crucial variant surface glycoprotein protective coat. TbnSMase is therefore genetically validated as a drug target against African trypanosomes, and suggests that interfering with the endocytic transport of variant surface glycoprotein is a highly desirable strategy for drug development against African trypanosomasis.

Molecular Microbiology published new progress about Biological transport. 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

Xia, Chengjie; Xu, Weiming; Ai, Xin; Zhu, Yingqi; Geng, Ping; Niu, Yijun; Zhu, Haiyan; Zhou, Wei; Huang, Hai; Shi, Xunlong published the artcile< Autophagy and exosome coordinately enhance macrophage M1 polarization and recruitment in influenza A virus infection>, SDS of cas: 6823-69-4, the main research area is influenza A virus infection autophagy exosome macrophage M1 polarization; CD63; LC3; influenza; macrophage; polarization.

Influenza A virus infection results in viral pneumonia, which is often accompanied by the infiltration and recruitment of macrophages, overactivation of inflammatory responses, and obvious cell autophagy and exosome production However, little is known about the roles of autophagy and exosome production in these inflammatory responses. In this study, multiple methods, such as flow cytometry, real-time quant. reverse transcription-polymerase chain reaction, immune-fluorescence technol., and western blot, were applied to explore the possible effects of autophagy and exosome production by H1N1-infected host cells. It was observed that a high number of polarized macrophages (CD11b+/F4/80+/ CD86+) were recruited to the lung tissues of infected mice, which could be mimicked by tracking the movement of macrophages to H1N1-infected cells in vitro (transwell assays). Furthermore, there was some coordinated upregulation of M1 polarization signs (iNOS/Arg-1 bias) as well as autophagy (LC3) and exosome (CD63) biomarkers in the infected macrophages and epithelial cells. Moreover, exosomes extracted from the supernatant of virus-infected cells were shown to promote the recruitment and polarization of more peritoneal macrophages than the normal group. The fluorescence colocalization of LC3-CD63 and the inhibition of autophagy and exosome signaling pathway further revealed that H1N1 infection seemed to sequentially activate the M1 polarization and recruitment of macrophages via autophagy-exosome dependent pathway. Autophagy and exosome production coordinately enhance the M1 polarization and recruitment of macrophages in influenza virus infection, which also provides potential therapeutic targets.

Frontiers in Immunology published new progress about Adhesion G protein-coupled receptor E1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Yang, Jin; Cao, Lu-Lu; Wang, Xi-Peng; Guo, Wei; Guo, Ruo-Bing; Sun, Yu-Qin; Xue, Teng-Fei; Cai, Zhen-Yu; Ji, Juan; Cheng, Hong; Sun, Xiu-Lan published the artcile< Neuronal extracellular vesicle derived miR-98 prevents salvageable neurons from microglial phagocytosis in acute ischemic stroke>, Formula: C30H30Cl2N6O2, the main research area is ischemic stroke neuron extracellular vesicle microRNA98 microglia phagocytosis.

Extracellular vesicles (EVs), as a novel intercellular communication carrier transferring cargo microRNAs (miRNAs), could play important roles in the brain remodeling process after ischemic stroke. However, the detailed mechanisms involved in EVs derived miRNAs-mediated cellular interactions in the brain remain unclear. Several studies indicated that microRNA-98 (miR-98) might participate in the pathogenesis of ischemic stroke. Here, we showed that expression of miR-98 in penumbra field kept up on the first day but dropped sharply on the 3rd day after ischemic stroke in rats, indicating that miR-98 could function as an endogenous protective factor post-ischemia. Overexpression of miR-98 targeted inhibiting platelet activating factor receptor-mediated microglial phagocytosis to attenuate neuronal death. Furthermore, we showed that neurons transferred miR-98 to microglia via EVs secretion after ischemic stroke, to prevent the stress-but-viable neurons from microglial phagocytosis. Therefore, we reveal that EVs derived miR-98 act as an intercellular signal mediating neurons and microglia communication during the brain remodeling after ischemic stroke. The present work provides a novel insight into the roles of EVs in the stroke pathogenesis and a new EVs-miRNAs-based therapeutic strategy for stroke.

Cell Death & Disease published new progress about Allograft inflammatory factor 1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Formula: C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Liao, Wen; Ning, Yu; Xu, Hai-Jia; Zou, Wen-Zhong; Hu, Jing; Liu, Xiang-Zhong; Yang, Yi; Li, Zhang-Hua published the artcile< BMSC-derived exosomes carrying microRNA-122-5p promote proliferation of osteoblasts in osteonecrosis of the femoral head>, COA of Formula: C30H30Cl2N6O2, the main research area is osteonecrosis microRNA osteoblast proliferation femoral head; RTK/Ras/MAPK signaling pathway; bone marrow mesenchymal stem cell; exosome; microRNA-122-5p; osteonecrosis of the femoral head; sprouty2.

The current study aims to explore the role of bone marrow (BM) MSCs (BMSCs)-derived exosomes carrying microRNA-122-5p (miR-122-5p) in ONFH rabbit models. First, rabbit models with ONFH were established. ONFH-related miRNAs were screened using the Gene Expression Omnibus (GEO) database. A gain-of-function study was performed to investigate the effect of miR-122-5p on osteoblasts and BMSCs and effects of exosomes carrying miR-122-5p on ONFH. Co-culture experiments for osteoblasts and BMSCs were performed to examine the role of exosomal miR-122-5p in osteoblast proliferation and osteogenesis. The target relationship between miR-122-5p and Sprouty2 (SPRY2) was tested. MiR-122, significantly decreased in ONFH in the GSE89587 expression profile, was screened. MiR-122-5p neg. regulated SPRY2 and elevated the activity of receptor tyrosine kinase (RTK), thereby promoting the proliferation and differentiation of osteoblasts. In vivo experiments indicated that bone mineral d. (BMD), trabecular bone volume (TBV), and mean trabecular plate thickness (MTPT) of femoral head were increased after over-expressing miR-122-5p in exosomes. Significant healing of necrotic femoral head was also observed Exosomes carrying over-expressed miR-122-5p attenuated ONFH development by down-regulating SPRY2 via the RTK/Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Findings in the present study may provide miR-122-5p as a novel biomarker for ONFH treatment.

Clinical Science published new progress about Animal gene, HLA-DR Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, COA of Formula: C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Xian, Xian; Cai, Li-Li; Li, Yang; Wang, Ran-Chao; Xu, Yu-Hao; Chen, Ya-Jie; Xie, Yu-Hang; Zhu, Xiao-Lan; Li, Yue-Feng published the artcile< Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression>, Electric Literature of 6823-69-4, the main research area is neuron secrete exosome miR9 5p m1 microglia polarization depression; Depression; Exosomes; Microglial polarization; Neuroinflammation; miR-9-5p.

Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurol. damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.

Journal of Nanobiotechnology published new progress about Antidepressants. 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

McCann, James V.; Liu, Amber; Musante, Luca; Erdbrugger, Uta; Lannigan, Joanne; Dudley, Andrew C. published the artcile< A miRNA signature in endothelial cell-derived extracellular vesicles in tumor-bearing mice>, Application of C30H30Cl2N6O2, the main research area is miRNA signature endothelial cellderived extracellular vesicle tumorbearing.

Extracellular vesicles (EVs) play important roles in tumor progression by altering immune surveillance, promoting vascular dysfunction, and priming distant sites for organotropic metastases. The miRNA expression patterns in circulating EVs are important diagnostic tools in cancer. However, multiple cell types within the tumor microenvironment (TME) including cancer cells and stromal cells (e.g. immune cells, fibroblasts, and endothelial cells, ECs) contribute to the pool of circulating EVs. Because EVs of different cellular origins have different functional properties, auditing the cargo derived from cell type-specific EVs in the TME is essential. Here, we demonstrate that a murine EC lineage-tracing model (Cdh5-CreERT2:ZSGreenl/s/l mice) can be used to isolate EC-derived extracellular vesicles (EC-EVs). We further show that purified ZSGreen+ EVs express expected EV markers, they are transferable to multiple recipient cells, and circulating EC-EVs from tumor-bearing mice harbor elevated levels of specific miRNAs (e.g. miR-30c, miR-126, miR-146a, and miR-125b) compared to non tumor-bearing counterparts. These results suggest that, in the tumor setting, ECs may systemically direct the function of heterotypic cell types either in the circulation or in different organ micro-environments via the cargo contained within their EVs.

Scientific Reports published new progress about Alcohols, C8-10, ethoxylated propoxylated Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Application of C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ma, Rong; Kutchy, Naseer A.; Hu, Guoku published the artcile< Astrocyte-Derived Extracellular Vesicle-Mediated Activation of Primary Ciliary Signaling Contributes to the Development of Morphine Tolerance>, Reference of 6823-69-4, the main research area is astrocyte extracellular vesicle primary ciliary signaling morphine; Astrocyte; Extracellular vesicle; Morphine tolerance; Primary cilia; Sonic hedgehog.

Morphine is used extensively in the clin. setting owing to its beneficial effects, such as pain relief; its therapeutic utility is limited because the prolonged use of morphine often results in tolerance and addiction. Astrocytes in the brain are a direct target of morphine action and play an essential role in the development of morphine tolerance. Primary cilia and the cilia-mediated sonic hedgehog (SHH) signaling pathways have been shown to play a role in drug resistance and morphine tolerance, resp. Extracellular vesicles (EVs) play important roles as cargo-carrying vesicles mediating communication among cells and tissues. C57BL/6N mice were administered morphine for 8 days to develop tolerance, which was determined using the tail-flick and hot plate assays. EVs were separated from astrocyte-conditioned media using either size exclusion chromatog. or ultracentrifugation approaches, followed by characterization of EVs using nanoparticle tracking anal. for EV size distribution and number, Western blotting for EV markers, and electron microscopy for EV morphol. Astrocytes were treated with EVs for 24 h, followed by assessing primary cilia by fluorescent immunostaining for primary cilia markers (ARL13B and acetylated tubulin). Morphine-tolerant mice exhibited an increase in primary cilia length and percentage of ciliated astrocytes. The levels of SHH protein were upregulated in morphine-stimulated astrocyte-derived EVs. SHH on morphine-stimulated astrocyte-derived EVs activated SHH signaling in astrocytes through primary cilia. Our in vivo study demonstrated that inhibition of either EV release or primary cilia prevents morphine tolerance in mice. EV-mediated primary ciliogenesis contributes to the development of morphine tolerance.

Biological Psychiatry published new progress about ADP ribosylation factor-like protein ARL13B Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Reference of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Dong, Yuanlin; Liang, Feng; Huang, Lining; Fang, Fang; Yang, Guang; Tanzi, Rudolph E.; Zhang, Yiying; Quan, Qimin; Xie, Zhongcong published the artcile< The anesthetic sevoflurane induces tau trafficking from neurons to microglia>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is anesthetic sevoflurane tau trafficking neuron microglia.

Accumulation and spread of tau in Alzheimer’s disease and other tauopathies occur in a prion-like manner. However, the mechanisms and downstream consequences of tau trafficking remain largely unknown. We hypothesized that tau traffics from neurons to microglia via extracellular vesicles (EVs), leading to IL-6 generation and cognitive impairment. We assessed mice and neurons treated with anesthetics sevoflurane and desflurane, and applied nanobeam-sensor technol., an ultrasensitive method, to measure tau/p-tau amounts Sevoflurane, but not desflurane, increased tau or p-tau amounts in blood, neuron culture medium, or EVs. Sevoflurane increased p-tau amounts in brain interstitial fluid. Microglia from tau knockout mice took up tau and p-tau when treated with sevoflurane-conditioned neuron culture medium, leading to IL-6 generation. Tau phosphorylation inhibitor lithium and EVs generation inhibitor GW4869 attenuated tau trafficking. GW4869 mitigated sevoflurane-induced cognitive impairment in mice. Thus, tau trafficking could occur from neurons to microglia to generate IL-6, leading to cognitive impairment.

Communications Biology published new progress about Alzheimer disease. 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

Jiang, Dongdong; Gong, Fangyi; Ge, Xuhui; Lv, Chengtang; Huang, Chenyu; Feng, Shuang; Zhou, Zheng; Rong, Yuluo; Wang, Jiaxing; Ji, Chengyue; Chen, Jian; Zhao, Wene; Fan, Jin; Liu, Wei; Cai, Weihua published the artcile< Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes>, Formula: C30H30Cl2N6O2, the main research area is miR124 3p exosome neurotoxic microglia astrocyte spinal cord injury; Astrocytes; Exosomes; Microglia; Spinal cord injury; miR-124-3p/MYH9 axis.

Spinal cord injury (SCI) is a catastrophic injury that can cause irreversible motor dysfunction with high disability. Exosomes participate in the transport of miRNAs and play an essential role in intercellular communication via transfer of genetic material. However, the miRNAs in exosomes which derived from neurons, and the underlying mechanisms by which they contribute to SCI remain unknown. Methods: A contusive in vivo SCI model and a series of in vitro experiments were carried out to explore the therapeutic effects of exosomes. Then, a miRNA microarray anal. and rescue experiments were performed to confirm the role of neuron-derived exosomal miRNA in SCI. Western blot, luciferase activity assay, and RNA-ChIP were used to investigate the underlying mechanisms. Results: The results indicated that neuron-derived exosomes promoted functional behavioral recovery by suppressing the activation of M1 microglia and A1 astrocytes in vivo and in vitro. A miRNA array showed miR-124-3p to be the most enriched in neuron-derived exosomes. MYH9 was identified as the target downstream gene of miR-124-3p. A series of experiments were used to confirm the miR-124-3p/MYH9 axis. Finally, it was found that PI3K/AKT/NF-κB signaling cascades may be involved in the modulation of microglia by exosomal miR-124-3p. Conclusion: A combination of miRNAs and neuron-derived exosomes may be a promising, minimally invasive approach for the treatment of SCI.

Journal of Nanobiotechnology published new progress about Allograft inflammatory factor 1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Formula: C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ren, Lingyun; Chen, Shanshan; Yao, Dan; Yan, Hong published the artcile< OxLDL-stimulated macrophage exosomes promote proatherogenic vascular smooth muscle cell viability and invasion via delivering miR-186-5p then inactivating SHIP2 mediated PI3K/AKT/mTOR pathway>, SDS of cas: 6823-69-4, the main research area is lipoprotein macrophage exosome microRNA SHIP2 PI3K AKT atherosclerosis; Atherosclerosis; Exosomes; MiR-186–5p/SHIP2/PI3K/AKT/mTOR; OxLDL-stimulated-macrophages; Vascular smooth muscle cells.

The current study aimed to investigate the implication of microRNA (miRNA) profile in the linkage between oxidized low-d.-lipoprotein (oxLDL)-stimulated-macrophages (MΦ) exosomes and vascular smooth muscle cells (VSMCs) during atherosclerosis. VSMCs were treated by oxLDL-stimulated-MΦ with/without GW4869. MiRNA profile in oxLDL-stimulated-MΦ and untreated-MΦ was detected by microarray, then candidate miRNAs were proposed to RT-qPCR and functional validation in VSMCs. MiR-186-5p mimic/inhibitor was transfected into oxLDL-stimulated-MΦ, then its exosomes were used to VSMCs. Subsequently, miR-186-5p, SHIP2 and PI3K/AKT/mTOR pathway were modified alone or in combination in VSMCs. VSMCs viability, invasion and apoptosis were detected. OxLDL-stimulated-MΦ induced VSMCs viability, invasion, but repressed apoptosis (all P < 0.01); while after GW4869 treatment to delete exosomes, its effect was weakened (all P < 0.05). Totally 45 dysregulated miRNAs were identified in oxLDL-stimulated-MΦ vs. untreated-MΦ. The top-three dysregulated miRNAs (miR-186-5p, miR-21-5p, miR-320b) were elevated in VSMCs after oxLDL-stimulated-MΦ treatment (all P < 0.001); while only miR-186-5p mimic greatly enhanced VSMCs viability and invasion (both P < 0.01). Furthermore, miR-186-5p-overexpressed oxLDL-stimulated-MΦ exosomes promoted VSMCs viability, invasion, repressed apoptosis, while miR-186-5p-knockdown oxLDL-stimulated-MΦ exosomes exhibited opposite effect (all P < 0.05). MiR-186-5p neg. regulated SHIP2 in VSMCs and bound SHIP2 via luciferase-reporter-gene assay (all P < 0.05). SHIP2 overexpression decreased VSMCs viability, invasion, PI3K/AKT/mTOR pathway, increased apoptosis, and attenuated miR-186-5p-overexpression's effect on these functions (all P < 0.05). Besides, PI3K activator (740 Y-P) weakened SHIP2-overexpression's effect on VSMCs viability, invasion and apoptosis (all P < 0.05). In conclusion, oxLDL-stimulated-MΦ exosomes deliver miR-186-5p to inactivate SHIP2 mediated PI3K/AKT/mTOR pathway, then promote cell viability and invasion in VSMCs to accelerate atherosclerosis. Molecular Immunology 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