Category: 6823-69-4

Lin, Yu; Liu, Meihan; Chen, Enqi; Jiang, Wei; Shi, Weidong; Wang, Zhiyuan published the artcile< Bone marrow-derived mesenchymal stem cells microvesicles stabilize atherosclerotic plaques by inhibiting NLRP3-mediated macrophage pyroptosis>, Product Details of C30H30Cl2N6O2, the main research area is bone marrow stem cell microvesicle atherosclerotic plaque NLRP pyroptosis; Nod-like receptor protein 3; atherosclerosis; atherosclerotic plaques; bone marrow-derived mesenchymal stem cells microvesicles; macrophage; microRNA-223; pyroptosis.

Rupture of atherosclerotic plaques constitutes the major cause of thrombosis and acute ischemic coronary syndrome. Bone marrow-derived mesenchymal stem cells microvesicles (BMSCs-MVs) are reported to promote angiogenesis. This study investigated the role of BMSCs-MVs in stabilizing atherosclerotic plaques. The BMSCs-MVs in mice were isolated and identified. The mouse model of atherosclerosis was established, and mice were injected with BMSCs-MVs via the tail vein. The macrophage model with high glucose and oxidative damage was established and then incubated with BMSCs-MVs. Nod-like receptor protein 3 (NLRP3) expression, pyroptosis-related proteins, and inflammatory factors were detected. Actinomycin D was used to inhibit the secretion of BMSCs-MVs to verify the source of microRNA-223 (miR-223). The binding relationship between miR-223 and NLRP3 was predicted and verified. The BMSCs-MVs with knockdown of miR-223 were cocultured with bone marrow-derived macrophages with knockdown of NLRP3, and then levels of miR-223, NLRP3, pyroptosis-related proteins, and inflammatory factors were detected. The BMSCs-MVs could reduce the vulnerability index of atherosclerotic plaques and intima-media thickness in mice, and inhibit pyroptosis and inflammation. The BMSCs-MVs inhibited pyroptosis and inflammatory factors in macrophages. The BMSCs-MVs carried miR-223 to inhibit NLRP3 expression and reduce macrophage pyroptosis, thereby stabilizing the atherosclerotic plaques.

Cell Biology International published new progress about Angiogenesis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Product Details of C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Liang, Jinlian; Li, Hanhao; Mei, Jiaxin; Cao, Zhen; Tang, Yan; Huang, Rufei; Xia, Huan; Zhang, Qihao; Xiang, Qi; Yang, Yan; Huang, Yadong published the artcile< Sertoli cell-derived exosome-mediated transfer of miR-145-5p inhibits Leydig cell steroidogenesis by targeting steroidogenic factor 1>, Reference of 6823-69-4, the main research area is sertoli derived exosome miR145 5p leydig cell steroidogenesis adult; Leydig cell; Sertoli cell; exosome; miR-145-5p; testosterone.

In the mammalian testis, two distinct populations of Sertoli cells (SCs), the immature SCs (ISCs) and adult SCs (ASCs), play significant roles in regulating the development and function of Leydig cells. However, the effect of different SC types on the function of Leydig cells is poorly understood. Here, our study showed that miR-145-5p expression was significantly different in SCs at different stages, with the highest expression observed in ISCs. Exosomes mediate the transfer of miR-145-5p from ISCs to Leydig cells. Overexpression of miR-145-5p in Leydig cells significantly downregulated steroidogenic gene expression and inhibited testosterone synthesis. Addnl., miR-145-5p functioned by directly targeted steroidogenic factor-1 (Sf-1) and downregulated the expression of SF-1, which further downregulated the expression of steroidogenic genes, induced accumulation of lipid droplets, and eventually suppressed testosterone production These findings demonstrate that SC-derived miR-145-5p plays a significant role in regulating the functions of Leydig cells and may therefore serve as a diagnostic biomarker for male hypogonadism developmental abnormalities during puberty.

FASEB Journal published new progress about Adult, mammalian. 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

Zhou, Wenshuo; Woodson, Michael; Neupane, Biswas; Bai, Fengwei; Sherman, Michael B.; Choi, Kyung H.; Neelakanta, Girish; Sultana, Hameeda published the artcile< Exosomes serve as novel modes of tick-borne flavivirus transmission from arthropod to human cells and facilitates dissemination of viral RNA and proteins to the vertebrate neuronal cells>, Formula: C30H30Cl2N6O2, the main research area is Ixodes skin keratinocyte neuronal cell flavivirus; RNA transmission exosome Eprotein.

Mol. determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes with the size range of 30 to 200 nm in diameter Both pos. and neg. strands of LGTV RNA and viral envelope-protein were detected inside exosomes derived from arthropod, murine and human cells. Detection of Nonstructural 1 (NS1) protein in arthropod and neuronal exosomes further suggested that exosomes contain viral proteins. Viral RNA and proteins in exosomes derived from tick and mammalian cells were secured, highly infectious and replicative in all tested evaluations. Treatment with GW4869, a selective inhibitor that blocks exosome release affected LGTV loads in both arthropod and mammalian cell-derived exosomes. Transwell-migration assays showed that exosomes derived from infected-brain-microvascular endothelial cells (that constitute the blood-brain barrier) facilitated LGTV RNA and protein transmission, crossing of the barriers and infection of neuronal cells. Neuronal infection showed abundant loads of both tick-borne LGTV and mosquito-borne West Nile virus RNA in exosomes. Our data also suggest that exosomemediated LGTV viral transmission is clathrin-dependent. Collectively, our results suggest that flaviviruses uses arthropod-derived exosomes as a novel means for viral RNA and protein transmission from the vector, and the vertebrate exosomes for dissemination within the host that may subsequently allow neuroinvasion and neuropathogenesis.

PLoS Pathogens published new progress about Blood vessel. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Formula: C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Jung, Anna Lena; Herkt, Christina Elena; Schulz, Christine; Bolte, Kathrin; Seidel, Kerstin; Scheller, Nicoletta; Sittka-Stark, Alexandra; Bertrams, Wilhelm; Schmeck, Bernd published the artcile< Legionella pneumophila infection activates bystander cells differentially by bacterial and host cell vesicles>, Synthetic Route of 6823-69-4, the main research area is Legionella macrophage outer membrane vesicle GW4869 toll like receptor.

Extracellular vesicles from eukaryotic cells and outer membrane vesicles (OMVs) released from gram-neg. bacteria have been described as mediators of pathogen-host interaction and intercellular communication. Legionella pneumophila (L. pneumophila) is a causative agent of severe pneumonia. The differential effect of bacterial and host cell vesicles in L. pneumophila infection is unknown so far. We infected THP-1-derived or primary human macrophages with L. pneumophila and isolated supernatant vesicles by differential centrifugation. We observed an increase of exosomes in the 100 k pellet by nanoparticle tracking anal., electron microscopy, and protein markers. This fraction addnl. contained Legionella LPS, indicating also the presence of OMVs. In contrast, vesicles in the 16 k pellet, representing microparticles, decreased during infection. The 100 k vesicle fraction activated uninfected primary human alveolar epithelial cells, A549 cells, and THP-1 cells. Epithelial cell activation was reduced by exosome depletion (anti-CD63, or GW4869), or blocking of IL-1β in the supernatant. In contrast, the response of THP-1 cells to vesicles was reduced by a TLR2-neutralizing antibody, UV-inactivation of bacteria, or – partially – RNase-treatment of vesicles. Taken together, we found that during L. pneumophila infection, neighboring epithelial cells were predominantly activated by exosomes and cytokines, whereas myeloid cells were activated by bacterial OMVs.

Scientific Reports published new progress about Alveolar epithelium. 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

Cui, Yigong; Fu, Shenglong; Sun, Dong; Xing, Junchao; Hou, Tianyong; Wu, Xuehui published the artcile< EPC-derived exosomes promote osteoclastogenesis through LncRNA-MALAT1>, Application of C30H30Cl2N6O2, the main research area is endothelial progenitor cell exosome; bone marrow derived macrophage osteoclastogenesis MALAT1; ITGB1; LncRNA-MALAT1; bone marrow-derived macrophages; bone repair; endothelial progenitor cells; miR-124; osteoclastogenesis.

Bone repair involves bone resorption through osteoclastogenesis and the stimulation of neovascularization and osteogenesis by endothelial progenitor cells (EPCs). However, the role of EPCs in osteoclastogenesis is unclear. In this study, we assess the effects of EPC-derived exosomes on the migration and osteoclastic differentiation of primary mouse bone marrow-derived macrophages (BMMs) in vitro using immunofluorescence, western blotting, RT-PCR and Transwell assays. We also evaluated the effects of EPC-derived exosomes on the homing and osteoclastic differentiation of transplanted BMMs in a mouse bone fracture model in vivo. We found that EPCs cultured with BMMs secreted exosomes into the medium and, compared with EPCs, exosomes had a higher expression level of LncRNA-MALAT1. We confirmed that LncRNA-MALAT1 directly binds to miR-124 to neg. control miR124 activity. Moreover, overexpression of miR-124 could reverse the migration and osteoclastic differentiation of BMMs induced by EPC-derived exosomes. A dual-luciferase reporter assay indicated that the integrin ITGB1 is the target of miR-124. Mice treated with EPC-derived exosome-BMM co-transplantations exhibited increased neovascularization at the fracture site and enhanced fracture healing compared with those treated with BMMs alone. Overall, our results suggest that EPC-derived exosomes can promote bone repair by enhancing recruitment and differentiation of osteoclast precursors through LncRNA-MALAT1.

Journal of Cellular and Molecular Medicine published new progress about Argonaute proteins 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

Kang, Ting; Jones, Tia M.; Naddell, Clayton; Bacanamwo, Methode; Calvert, John W.; Thompson, Winston E.; Bond, Vincent C.; Chen, Y. Eugene; Liu, Dong published the artcile< Adipose-derived stem cells induce angiogenesis via microvesicle transport of miRNA-31>, Name: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is adipose stem cell angiogenesis miRNA microvesicle transport; Adipose stem cell; Angiogenesis; Endothelial cell; Microvesicle; miRNA.

Cell secretion is an important mechanism for stem cell-based therapeutic angiogenesis, along with cell differentiation to vascular endothelial cells or smooth muscle cells. Cell-released microvesicles (MVs) have been recently implicated to play an essential role in intercellular communication. The purpose of this study was to explore the potential effects of stem cell-released MVs in proangiogenic therapy. We observed for the first time that MVs were released from adipose-derived stem cells (ASCs) and were able to increase the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Endothelial differentiation medium (EDM) preconditioning of ASCs upregulated the release of MVs and enhanced the angiogenic effect of the released MVs in vitro. RNA ana lysis revealed that microRNA was enriched in ASC-released MVs and that the level of microRNA-31 (miR-31) in MVs was notably elevated upon EDM-preconditioning of MV-donor A5Cs. Further studies exhibited that miR-31 in MVs contributed to the migration and tube formation of HUVECs, microvessel outgrowth of mouse aortic rings, and vascular formation of mouse Matrigel plugs. Moreover, factor-inhibiting HIF-1, an antiangiogenic gene, was identified as the target of miR-31 in HUVECs. Our findings provide the first evidence that MVs from ASCs, particularly from EDM-preconditioned ASCs, promote angiogenesis and the delivery of miR-31 may contribute the proangiogenic effect.

Stem Cells Translational Medicine published new progress about Cell differentiation. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Name: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Su, Zhen; Yuan, Yanggang; Yu, Manshu; Liu, Yan; Klein, Janet D.; Wang, Xiaonan H. published the artcile< Electrically stimulated acupuncture increases renal blood flow through exosome-carried miR-181>, Computed Properties of 6823-69-4, the main research area is renal blood flow exosome microRNA 181 acupuncture; Acu/LFES; angiotensinogen; exosome; microRNA; renal blood flow.

Acupuncture with low-frequency elec. stimulation (Acu/LFES) can prevent muscle atrophy by increasing muscle protein anabolism in mouse models of chronic kidney disease. During the treatment of muscle wasting, we found that Acu/LFES on the gastrocnemius muscle of the leg enhances renal blood flow. We also found that Acu/LFES increases exosome abundance and alters exosome-associated microRNA expression in the circulation. When exosome secretion was blocked using GW4869, the Acu/LFES-induced increase in renal blood flow was limited. This provided evidence that the increased renal blood flow is exosome mediated. To identify how exosomes regulate renal blood flow, we performed microRNA deep sequencing in exosomes isolated from treated and untreated mouse serum and found that the 34 microRNAs are altered by Acu/LFES. In particular, miR-181d-5p is increased in the serum exosome of Acu/LFES-treated mice. In silico searching suggested that miR-181d-5p could target angiotensinogen. Using a luciferase reporter assay, we demonstrated that miR-181 directly inhibits angiotensinogen. When Acu/LFES-treated muscle was excised and incubated in culture medium, we found that the amount of exosomes and miR-181d-5p was increased in the medium providing evidence that Acu/LFES can increase miR-181 secretion. We conclude that Acu/LFES on leg hindlimb increases miR-181 in serum exosome leading to increased renal blood flow.

American Journal of Physiology published new progress about Acupuncture. 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

Figuera-Losada, Mariana; Stathis, Marigo; Dorskind, Joelle M.; Thomas, Ajit G.; Bandaru, Veera Venkata Ratnam; Yoo, Seung-Wan; Westwood, Nicholas J.; Rogers, Graeme W.; McArthur, Justin C.; Haughey, Norman J.; Slusher, Barbara S.; Rojas, Camilo published the artcile< Cambinol, a novel inhibitor of neutral sphingomyelinase 2 shows neuroprotective properties>, Application In Synthesis of 6823-69-4, the main research area is neurodegeneration cambinol sphingomyelinase 2 ceramide.

Ceramide is a bioactive lipid that plays an important role in stress responses leading to apoptosis, cell growth arrest and differentiation. Ceramide production is due in part to sphingomyelin hydrolysis by sphingomyelinases. In brain, neutral sphingomyelinase 2 (nSMase2) is expressed in neurons and increases in its activity and expression have been associated with pro-inflammatory conditions observed in Alzheimer’s disease, multiple sclerosis and human immunodeficiency virus (HIV-1) patients. Increased nSMase2 activity translates into higher ceramide levels and neuronal cell death, which can be prevented by chem. or genetic inhibition of nSMase2 activity or expression. However, to date, there are no soluble, specific and potent small mol. inhibitor tool compounds for in vivo studies or as a starting point for medicinal chem. optimization. Moreover, the majority of the known inhibitors were identified using bacterial, bovine or rat nSMase2. In an attempt to identify new inhibitor scaffolds, two activity assays were optimized as screening platform using the recombinant human enzyme. First, active hits were identified using a fluorescence-based high throughput compatible assay. Then, hits were confirmed using a 14C sphingomyelin-based direct activity assay. Pharmacol. active compounds and approved drugs were screened using this strategy which led to the identification of cambinol as a novel uncompetitive nSMase2 inhibitor (Ki = 7 μM). The inhibitory activity of cambinol for nSMase2 was approx. 10-fold more potent than for its previously known target, silence information regulator 1 and 2 (SIRT1/2). Cambinol decreased tumor necrosis factor-α or interleukin-1 β-induced increases of ceramide and cell death in primary neurons. A preliminary study of cambinol structure and activity allowed the identification of the main structural features required for nSMase2 inhibition. Cambinol and its analogs may be useful as nSMase2 inhibitor tool compounds to prevent ceramide-dependent neurodegeneration.

PLoS One published new progress about Alzheimer disease. 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

Takahashi, Eriko; Inanami, Osamu; Asanuma, Taketoshi; Kuwabara, Mikinori published the artcile< Effects of ceramide inhibition on radiation-induced apoptosis in human leukemia MOLT-4 cells>, Reference of 6823-69-4, the main research area is ceramide radiation apoptosis leukemia MOLT4 cell.

In the present study, using inhibitors of ceramide synthase (fumonisin B1), ketosphinganine synthetase (L-cycloserine), acid sphingomyelinase (D609 and desipramine) and neutral sphingomyelinase (GW4869), the role of ceramide in x-ray-induced apoptosis was investigated in MOLT-4 cells. The diacylglycerol kinase (DGK) assay showed that the intracellular concentration of ceramide increased time-dependently after X irradiation of cells, and this radiation-induced accumulation of ceramide did not occur prior to the appearance of apoptotic cells. Treatment with D609 significantly inhibited radiation-induced apoptosis, but did not inhibit the increase of intracellular ceramide. Treatment with desipramine or GW4869 prevented neither radiation-induced apoptosis nor the induced increase of ceramide. On the other hand, fumonisin B1 and L-cycloserine had no effect on the radiation-induced induction of apoptosis, in spite of significant inhibition of the radiation-induced ceramide. From these results, it was suggested that the increase of the intracellular concentration of ceramide was not essential for radiation-induced apoptosis in MOLT-4 cells.

Journal of Radiation Research published new progress about Ceramides 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

Ye, Chao; Zheng, Fen; Xu, Tao; Wu, Nan; Tong, Ying; Xiong, Xiao-Qing; Zhou, Ye-Bo; Wang, Jue-Jin; Chen, Qi; Li, Yue-Hua; Zhu, Guo-Qing; Han, Ying published the artcile< Norepinephrine acting on adventitial fibroblasts stimulates vascular smooth muscle cell proliferation via promoting small extracellular vesicle release>, Application In Synthesis of 6823-69-4, the main research area is vascular smooth muscle cell proliferation fibroblast extracellular vesicle norepinephrine; adventitial fibroblasts; angiotensin converting enzyme; extracellular vesicle; hypertension; norepinephrine; vascular smooth muscle cell.

Excessive sympathetic activity and norepinephrine (NE) release play crucial roles in the pathogeneses of hypertension. Sympathetic fibers innervate adventitia rather than media of arteries. However, the roles of NE in adventitial fibroblasts (AFs) are unknown. This study investigated the roles of NE in regulating AFs-derived extracellular vesicles (EVs) release and vascular smooth muscle cells (VSMCs) proliferation in hypertension. AFs and VSMCs were prepared from aorta of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). AFs were treated with NE (10μM) for 24 h (every 6 h, 4 times), and cultured in exosomes-depleted medium for 48 h. EVs were isolated from AFs medium with ultracentrifugation for identification and transfer to VSMCs. NE promoted AFs phenotypic transformation and proliferation, which were prevented by α-receptor antagonist phentolamine rather than β-receptor antagonist propranolol. NE-treated AFs conditioned medium stimulated VSMCs proliferation, which was inhibited by either exosome inhibitor GW4869 or phentolamine. NE increased small EVs number, diameter and angiotensin converting enzyme (ACE) contents. The NE-induced EVs release was abolished by GW4869. The EVs from NE-treated AFs stimulated VSMCs proliferation, which was prevented by angiotensin II type 1 receptor antagonist losartan. The EVs from the ACE knockdown-treated AFs showed lower ACE contents, and lost their roles in stimulating VSMCs proliferation. NE promotes AFs-derived small EVs release and ACE transfer, and then causes VSMCs proliferation in hypertension. Intervention of AFs-derived EVs release may be potential therapeutics for excessive sympathetic activation-related vascular remodeling in hypertension.

Theranostics published new progress about Angiotensin AT1 receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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