Category: 6823-69-4

Ibanez, Francesc; Montesinos, Jorge; Area-Gomez, Estela; Guerri, Consuelo; Pascual, Maria published the artcile< Ethanol Induces Extracellular Vesicle Secretion by Altering Lipid Metabolism through the Mitochondria-Associated ER Membranes and Sphingomyelinases>, Computed Properties of 6823-69-4, the main research area is sphingomyelinase extracellular vesicle secretion lipid metabolism; alcohol; extracellular vesicles; lipid metabolism; microglia; mitochondria-associated ER membranes; neuroinflammation; phospholipids; sphingomyelinases.

Recent evidence pinpoints extracellular vesicles (EVs) as key players in intercellular communication. Given the importance of cholesterol and sphingomyelin in EV biol., and the relevance of mitochondria-associated endoplasmic reticulum membranes (MAMs) in cholesterol/sphingomyelin homeostasis, we evaluated if MAMs and sphingomyelinases (SMases) could participate in ethanol-induced EV release. EVs were isolated from the extracellular medium of BV2 microglia treated or not with ethanol (50 and 100 mM). Radioactive metabolic tracers combined with thin layer chromatog. were used as quant. methods to assay phospholipid transfer, SMase activity and cholesterol uptake/esterification. Inhibitors of SMase (desipramine and GW4869) and MAM (cyclosporin A) activities were also utilized. Our data show that ethanol increases the secretion and inflammatory mol. concentration of EVs. Ethanol also upregulates MAM activity and alters lipid metabolism by increasing cholesterol uptake, cholesterol esterification and SMase activity in microglia. Notably, the inhibition of either SMase or MAM activity prevented the ethanol-induced increase in EV secretion. Collectively, these results strongly support a lipid-driven mechanism, specifically via SMases and MAM, to explain the effect of ethanol on EV secretion in glial cells.

International Journal of Molecular Sciences published new progress about Endoplasmic reticulum. 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

Gao, Xiao; Xiong, Ye; Li, Qizhao; Han, Min; Shan, Dezhi; Yang, Guozheng; Zhang, Shouji; Xin, Danqing; Zhao, Rongrong; Wang, Zhen; Xue, Hao; Li, Gang published the artcile< Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage>, Quality Control of 6823-69-4, the main research area is brain injury subarachnoid hemorrhage PTEN Akt mesenchymal stromal cell.

Abstract: Patients with subarachnoid hemorrhage (SAH) often suffer from cognitive function impairments even when they have received proper treatment, such as the clipping or coiling of aneurysms, and this causes problems with returning to work and burdens the family. Increasing attention has been paid to mesenchymal stem cell (MSC)-derived extracellular vesicle (MSC-EV) as promising therapeutic vesicles for stroke management. In this study, we explored the potential role of MSC-EV in a rat model of SAH. We observed that MSC-EV ameliorated early brain injury (EBI) after SAH by reducing the apoptosis of neurons and that SAH induced an increase in the expression level of miR-21 in the prefrontal cortex and hippocampus. In addition, using miRNA profiling and CSF sequencing data from the exRNA Atlas, we demonstrated that EV-derived miR-21 protected neurons from apoptosis and alleviated SAH-induced cognitive dysfunction. The neuroprotective role of MSC-EV was abrogated by miR-21 knockdown or the administration of MK2206, a PTEN/Akt inhibitor. Overall, our results suggest that MSC-EV promotes neuronal survival and alleviates EBI after SAH through transferring miR-21 to recipient neurons.

Cell Death & Disease published new progress about Animal gene, Bcl-2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Quality Control of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Fang, Fang; Guo, Chunfeng; Zheng, Weinan; Wang, Qin; Zhou, Limei published the artcile< Exosome-Mediated Transfer of miR-1323 from Cancer-Associated Fibroblasts Confers Radioresistance of C33A Cells by Targeting PABPN1 and Activating Wnt/beta-Catenin Signaling Pathway in Cervical Cancer>, SDS of cas: 6823-69-4, the main research area is miR1323 PABPN1 Wnt beta catenin signaling cervical cancer; Cervical cancer; GSK-3β; IGF2BP1; PABPN1; Radioresistance; miR-1323.

Plenty of pieces of evidence suggest that the resistance to radiotherapy greatly influences the therapeutic effect in cervical cancer (CCa). MicroRNAs (miRNAs) have been reported to regulate cellular processes by acting as tumor suppressors or promoters, thereby driving radioresistance or radiosensitivity. Meanwhile, it has been reported that microRNA-1323 (miR-1323) widely participates in cancer progression and radiotherapy effects. However, the role of miR-1323 is still not clear in CCa. Hence, in this study, we are going to investigate the mol. mechanism of miR-1323 in CCa cells. In the beginning, miR-1323 was found aberrantly upregulated in CCa cells via RT-qPCR assay. Functional assays indicated that miR-1323 was transferred by cancer-associated fibroblasts-secreted (CAFs-secreted) exosomes and miR-1323 downregulation suppressed cell proliferation, migration, invasion, and increased cell radiosensitivity in CCa. Mechanism assays demonstrated that miR-1323 targeted poly(A)-binding protein nuclear 1 (PABPN1). Besides, PABPN1 recruited insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to regulate glycogen synthase kinase 3 beta (GSK-3B) and influenced Wnt/beta-catenin signaling pathway. Therefore, rescue experiments were implemented to validate that PABPN1 overexpression rescued the inhibited cancer development and radioresistance induced by the miR-1323 inhibitor. In conclusion, miR-1323 was involved in CCa progression and radioresistance which might provide a novel insight for CCa treatment.

Reproductive Sciences published new progress about CD9 antigens 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

Deng, Lu; Wang, Chang; He, Chao; Chen, Li published the artcile< Bone mesenchymal stem cells derived extracellular vesicles promote TRAIL-related apoptosis of hepatocellular carcinoma cells via the delivery of microRNA-20a-3p>, Synthetic Route of 6823-69-4, the main research area is hepatocellular carcinoma bone mesenchymal stem cell TRAIL microRNA 20a3p; Hepatocellular carcinoma; TRAIL; bone mesenchymal stem cells; c-FLIP; extracellular vesicles; miR-20a-39.

Bone mesenchymal stem cells (BMSCs) have been widely researched in cancer treatment, including hepatocellular carcinoma (HCC). This study intended to discuss the mechanism of miR-20a-3p in BMSCs-extracellular vesicles (EVs) in HCC apoptosis. BMSCs were isolated and identified. EVs derived from BMSCs were extracted and identified. After overexpressing or inhibiting miR-20a-3p expression in BMSCs, EVs were extracted and acted on HCC cells and transplanted tumors. HCC cell apoptosis in the treatment of BMSCs-conditioned medium, BMSCs-EVs and/or miR-20a-3p mimic/inhibitor was evaluated, with the detection of levels of TRAIL and TRAIL-related proteins. A functional rescue experiment about c-FLIP was carried out in HCC cells. The target binding relationship between miR-20a-3p and c-FLIP was detected. The s.c. tumorigenesis model of mice was established and injected with BMSCs-EVs to estimate the effect of BMSCs-EVs-miR-20a-3p on HCC growth. EVs isolated from BMSCs conditioned medium promoted the apoptosis of HCC cells. After BMSCs-EVs treatment, TRAIL levels, downstream proteins and miR-20a-3p were increased significantly, but the expression of c-FLIP was decreased. miR-20a-3p could target c-FLIP. BMSCs-EVs inhibited the growth of HCC cells, decreased c-FLIP expression, increased TRAIL levels, and promote the of HCC cell apoptosis. BMSCs-EVs with overexpressing miR-20a-3p further enhanced the apoptotic effect of HCC cells in vitro and in vivo. BMSCs-EVs-carried miR-20a-3p targets c-FLIP and increases TRAIL levels in HCC cells, thus promoting TRAIL-related apoptosis.

Cancer Biomarkers published new progress about Antigens, Thy-1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Rong, Yuluo; Ji, Chengyue; Wang, Zhuanghui; Ge, Xuhui; Wang, Jiaxing; Ye, Wu; Tang, Pengyu; Jiang, Dongdong; Fan, Jin; Yin, Guoyong; Liu, Wei; Cai, Weihua published the artcile< Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury>, Safety of p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is traumatic spinal cord injury CCL2 astrocyte microglia neuronal apoptosis; Astrocyte; CCL2; Microglia; Neuron; Small extracellular vesicles; Spinal cord injury.

Spinal cord injury (SCI) is a severe traumatic disease which causes high disability and mortality rates. The mol. pathol. features after spinal cord injury mainly involve the inflammatory response, microglial and neuronal apoptosis, abnormal proliferation of astrocytes, and the formation of glial scars. However, the microenvironmental changes after spinal cord injury are complex, and the interactions between glial cells and nerve cells remain unclear. Small extracellular vesicles (sEVs) may play a key role in cell communication by transporting RNA, proteins, and bioactive lipids between cells. Few studies have examined the intercellular communication of astrocytes through sEVs after SCI. The inflammatory signal released from astrocytes is known to initiate microglial activation, but its effects on neurons after SCI remain to be further clarified. Electron microscopy (TEM), nanoparticle tracking anal. (NTA), and western blotting were applied to characterize sEVs. We examined microglial activation and neuronal apoptosis mediated by astrocyte activation in an exptl. model of acute spinal cord injury and in cell culture in vitro. Our results indicated that astrocytes activated after spinal cord injury release CCL2, act on microglia and neuronal cells through the sEV pathway, and promote neuronal apoptosis and microglial activation after binding the CCR2. Subsequently, the activated microglia release IL-1β, which acts on neuronal cells, thereby further aggravating their apoptosis. This study elucidates that astrocytes interact with microglia and neurons through the sEV pathway after SCI, enriching the mechanism of CCL2 in neuroinflammation and spinal neurodegeneration, and providing a new theor. basis of CCL2 as a therapeutic target for SCI.

Journal of Neuroinflammation published new progress about Apoptosis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Safety of p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Su, Hong; Qiao, Jiao; Hu, Jinxiu; Li, Yanmei; Lin, Jiangong; Yu, Qun; Zhen, Junhui; Ma, Qiqi; Wang, Qianhui; Lv, Zhimei; Wang, Rong published the artcile< Podocyte-derived extracellular vesicles mediate renal proximal tubule cells dedifferentiation via microRNA-221 in diabetic nephropathy>, Synthetic Route of 6823-69-4, the main research area is microRNA221 vesicle renal proximal tubule signaling diabetic nephropathy; Dedifferentiation; Extracellular vesicles; Podocytes; Proximal tubular epithelial cells; Wnt/β-catenin signaling; miR-221.

Podocyte injury is a key event in the initiation of Diabetic nephropathy (DN). Tubulointerstitium, especially the proximal tubule has been regarded as a target of injury. In the present study, we showed that podocytes induced dedifferentiation of proximal tubular epithelial cells(PTECs) in high-glucose conditions and extracellular vesicles (EVs) mediates the interaction. Then we extracted and identified these EVs derived from podocytes as exosome, further, the EVs induced PTECs dedifferentiation. Total microRNA(miRNA) expression of podocyte-derived EVs was extracted and miR-221 expression was remarkably increased. By making use of the miRNA gain- and loss-of-function approaches, we observed that miR-221 mediated PTECs dedifferentiation. In addition, a dual-luciferase reporter assay confirmed that miR-221 direct target DKK2, which was an inhibitor of Wnt signaling, and overexpression of miR-221 significantly resulted in β-catenin nuclear accumulation. Moreover, we regulated the expression of β-catenin and demonstrated that miR-221 in EVs mediated proximal tubule cells injury through Wnt/β-catenin signaling. Furthermore, inhibition of miR-221 in diabetic mice reversed the abnormal expression of PTECs dedifferentiation related protein. These findings provide unique insights in the mechanisms of proximal tubule cell injury in diabetic nephropathy.

Molecular and Cellular Endocrinology 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, Synthetic Route of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Hu, Yibing; Yan, Chang; Mu, Lei; Huang, Kaiyu; Li, Xiaolan; Tao, Deding; Wu, Yaqun; Qin, Jichao published the artcile< Fibroblast-derived exosomes contribute to chemoresistance through priming cancer stem cells in colorectal cancer>, Name: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is fibroblast exosome chemoresistance colorectal cancer stem cell.

Chemotherapy resistance observed in patients with colorectal cancer (CRC) may be related to the presence of cancer stem cells (CSCs), but the underlying mechanism(s) remain unclear. Carcinoma-associated fibroblasts (CAFs) are intimately involved in tumor recurrence, and targeting them increases chemo-sensitivity. We investigated whether fibroblasts might increase CSCs thus mediating chemotherapy resistance. CSCs were isolated from either patient-derived xenografts or CRC cell lines based on expression of CD133. First, CSCs were found to be inherently resistant to cell death induced by chemotherapy. In addition, fibroblast-derived conditioned medium (CM) promoted percentage, clonogenicity and tumor growth of CSCs (i.e., CD133+ and TOP-GFP+) upon treatment with 5-fluorouracil (5-Fu) or oxaliplatin (OXA). Further investigations exhibited that exosomes, isolated from CM, similarly took the above effects. Inhibition of exosome secretion decreased the percentage, clonogenicity and tumor growth of CSCs. Altogether, our findings suggest that, besides targeting CSCs, new therapeutic strategies blocking CAFs secretion even before chemotherapy shall be developed to gain better clin. benefits in advanced CRCs.

PLoS One published new progress about CD133 antigens Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Gu, Y. Y.; Yu, J.; Zhang, J. F.; Wang, C. published the artcile< Suppressing the secretion of exosomal miR-19b by GW4869 could regulate oxaliplatin sensitivity in colorectal cancer>, Safety of p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is oxaliplatin MiR19b GW4869 colorectal cancer.

Oxaliplatin is commonly used in managing malignancy, including colorectal cancer. While treatment oftn fails due to decreased drug sensitivity, the mechanisms involved are not clear. In this study, we investigate how exosomal miR-19b participates in oxaliplatin sensitivity and then prove that miR-19b down-regulates oxaliplatin sensitivity of sw480 cells. We found that suppressing the secretion of exosomal miR-19b with gw4869 promotes sw480 cell oxaliplatin sensitivity. Our combined results demonstrate for the first time that miR-19b regulates the oxaliplatin sensitivity of sw480 cells and provides a unique mechanism mediated by gw4869 to modulate oxaliplatin sensitivity by suppressing exosomal miR-19b release.

Neoplasma published new progress about Bioinformatics. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Safety of p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Li, Shichao; Gao, Yuanfeng; Liu, Ye; Li, Jing; Yang, Xiyan; Hu, Roumu; Liu, Jia; Zhang, Yuan; Zuo, Kun; Li, Kuibao; Yin, Xiandong; Chen, Mulei; Zhong, Jiuchang; Yang, Xinchun published the artcile< Myofibroblast-Derived Exosomes Contribute to Development of a Susceptible Substrate for Atrial Fibrillation>, Name: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is atrial fibrillation myofibroblast cardiomyocyte exosome; Atrial fibrillation; Exosome; L-type calcium channel; Paracrine communication.

Atrial fibrosis plays a critical role in atrial fibrillation (AF). A key event in the pathogenesis of fibrosis is the activation of fibroblasts (FBs) into myofibroblasts (MFBs). Paracrine factors released from MFBs lead to ion channel expression changes in cardiomyocytes (CMs). Downregulation of L-type calcium channel Cav1.2 expression is a hallmark of AF-associated ionic remodeling. However, whether exosome-mediated crosstalk between MFBs and CMs regulates Cav1.2 expression remains unknown. Atrial FBs and CMs were isolated and cultured from neonatal rats by enzymic digestion. Untreated FBs expressed limited amounts of alpha smooth muscle actin (α-SMA), while angiotensin II induced a significant upregulation of α-SMA-expressing MFBs. Co-cultures of MFBs and CMs resulted in downregulation of Cav1.2 expression in CMs, which was largely abolished by pretreatment of MFBs with exosomal inhibitor GW4869. Addnl., the adrenergic receptor agonist-elicited Ca2 influx signals in CMs were remarkably attenuated by pretreatment with MFB-derived Exos, corresponding to the paralleled change in Cav1.2 expression. Finally, miR-21-3p, a potential Cav1.2-inhibitory miRNA, was enriched in MFB-derived Exos and upregulated in CMs in response to MFB-derived Exos. We uncover an Exo-mediated crosstalk between MFBs and CMs, contributing to increased vulnerability to AF by reducing the expression of Cav1.2 in CMs.

Cardiology published new progress about Atrial fibrillation. 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

Guo, Belinda B.; Bellingham, Shayne A.; Hill, Andrew F. published the artcile< The Neutral Sphingomyelinase Pathway Regulates Packaging of the Prion Protein into Exosomes>, Computed Properties of 6823-69-4, the main research area is neutral sphingomyelinase packaging prion protein exosome; Ceramide; Exosome; Exosomes; Extracellular Vesicles; Neutral Sphingomyelinase; Prion; Prion Disease; nSMase2.

Prion diseases are a group of transmissible, fatal neurodegenerative disorders associated with the misfolding of the host-encoded prion protein, PrPC, into a disease-associated form, PrPSc. The transmissible prion agent is principally formed of PrPSc itself and is associated with extracellular vesicles known as exosomes. Exosomes are released from cells both in vitro and in vivo, and have been proposed as a mechanism by which prions spread intercellularly. The biogenesis of exosomes occurs within the endosomal system, through formation of intraluminal vesicles (ILVs), which are subsequently released from cells as exosomes. ILV formation is known to be regulated by the endosomal sorting complexes required for transport (ESCRT) machinery, although an alternative neutral sphingomyelinase (nSMase) pathway has been suggested to also regulate this process. Here, we investigate a role for the nSMase pathway in exosome biogenesis and packaging of PrP into these vesicles. Inhibition of the nSMase pathway using GW4869 revealed a role for the nSMase pathway in both exosome formation and PrP packaging. In agreement, targeted knockdown of nSMase1 and nSMase2 in mouse neurons using lentivirus-mediated RNAi also decreases exosome release, demonstrating the nSMase pathway regulates the biogenesis and release of exosomes. We also demonstrate that PrPC packaging is dependent on nSMase2, whereas the packaging of disease-associated PrPSc into exosomes occurs independently of nSMase2. These findings provide further insight into prion transmission and identify a pathway which directly assists exosome-mediated transmission of prions.

Journal of Biological Chemistry published new progress about Aggregation. 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