Month: October 2022

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

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

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

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

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

Miao, Zhuang; Li, Yuanyuan; Mao, Fengbiao; Zhang, Jianghong; Sun, Zhong Sheng; Wang, Yan published the artcile< Prenatal witness stress induces intergenerational anxiety-like behaviors and altered gene expression profiles in male mice>, Related Products of 452-06-2, the main research area is prenatal witness stress intergenerational anxiety gene expression profile; Anxiety; Prenatal stress; Psychological stress; Sex difference; Stress resilience.

Prenatal cues imposed on an organism can exert long-term and even cross-generational influences on the physiol. and behaviors. To date, numerous rodent models have been developed to mimic the effects of prenatal phys. stress on offspring. Whether psychol. stress during gestation exerts adverse influences on offspring remains investigated. Here, we report that prenatal witnessing the defeat process of the mated partner induces anxiety-like behaviors in F1 male, but not female offspring. These abnormal behaviors were not present in the F2 generation, indicating a sex-specific intergenerational effects. Genome-wide transcriptional profiling identified 71 up-regulated and 120 down-regulated genes shared in F0 maternal and F1 male hippocampus. F0 and F1 hippocampi also shared witness stress-sensitive and -resistant genes. Whole transcriptome comparison reveals that F1 dentate gyrus showed differential expression profiles from hippocampus. Few differentially expressed genes were identified in the dentate gyrus of F1 stress female mice, explaining why females were resistant to the stress. Finally, candidate drugs as the potential treatment for psychol. stress were predicted according to transcriptional signatures, including the histone deacetylase inhibitor and dopamine receptor agonist. Our work provides a new model for better understanding the mol. basis of prenatal psychol. stress, highlighting the complexity of stress and sex factors on emotion and behaviors.

Neuropharmacology published new progress about Adrenoceptor agonists. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Related Products of 452-06-2.

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

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

Li, Na; Yang, Hong; Liu, Ke; Zhou, Liwei; Huang, Yuting; Cao, Danyan; Li, Yanlian; Sun, Yaoliang; Yu, Aisong; Du, Zhiyan; Yu, Feng; Zhang, Ying; Wang, Bingyang; Geng, Meiyu; Li, Jian; Xiong, Bing; Xu, Shilin; Huang, Xun; Liu, Tongchao published the artcile< Structure-Based Discovery of a Series of NSD2-PWWP1 Inhibitors>, Category: imidazoles-derivatives, the main research area is imidazole preparation SAR antitumor activity inhibitor.

A series of NSD2-PWWP1 inhibitors I (R = 4-cyanophenyl, 4-cyanonaphthalen-1-yl, 8-cyanoquinolin-5-yl, etc.; R1 = H, OMe, F, Cl, CF3; R2 = H, Me, OMe; R3 = aminomethyl, CHO, 4-aminopiperidin-1-yl, etc.), and further structure-based optimization resulted in a potent inhibitor compound I (R = 4-cyanonaphthalen-1-yl; R1 = R2 = Me; R3 = 4-aminopiperidin-1-yl) (II), that has high selectivity toward the NSD2-PWWP1 domain were reported. The detailed biol. evaluation revealed that compound II can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. The current discovery will provide a useful chem. probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition and pave the way to develop potential drugs targeting NSD2 protein.

Journal of Medicinal Chemistry published new progress about Amines Role: PAC (Pharmacological Activity), PKT (Pharmacokinetics), PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem