Tag: M.W=400-600

Choezom, Dolma; Gross, Julia Christina published the artcile< Neutral sphingomyelinase 2 controls exosome secretion by counteracting V-ATPase-mediated endosome acidification>, Application In Synthesis of 6823-69-4, the main research area is SMPD3 extracellular vesicle V ATPase maturation; Endosomal cargo sorting; Endosomal maturation; Intraluminal vesicles; Secretory multivesicular bodies; Small extracellular vesicles.

During endosome maturation, neutral sphingomyelinase 2 (nSMase2, encoded by SMPD3) is involved in budding of intraluminal vesicles (ILVs) into late endosomes or multivesicular bodies (MVBs). Fusion of these with the plasma membrane results in secretion of exosomes or small extracellular vesicles (sEVs). Here, we report that nSMase2 activity controls sEV secretion through modulation of vacuolar H+-ATPase (V-ATPase) activity. Specifically, we show that nSMase2 inhibition induces V-ATPase complex assembly that drives MVB lumen acidification and consequently reduces sEV secretion. Conversely, we further demonstrate that stimulating nSMase2 activity with the inflammatory cytokine TNFα (also known as TNF) decreases acidification and increases sEV secretion. Thus, we find that nSMase2 activity affects MVB membrane lipid composition to counteract V-ATPase-mediated endosome acidification, thereby shifting MVB fate towards sEV secretion.

Journal of Cell Science published new progress about CD81 antigens 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

Wu, Meiling; Liu, Xuemei; Li, Zihan; Huang, Xiaoyao; Guo, Hao; Guo, Xiaohe; Yang, Xiaoxue; Li, Bei; Xuan, Kun; Jin, Yan published the artcile< SHED aggregate exosomes shuttled miR-26a promote angiogenesis in pulp regeneration via TGF-β/SMAD2/3 signalling>, Formula: C30H30Cl2N6O2, the main research area is SHED exosome miR26a TGFbeta SMAD2 SMAD3 angiogenesis pulp regeneration; SHED aggregate; TGF-β signalling; angiogenesis; exosome; miR-26a; pulp regeneration.

Pulp regeneration brings big challenges for clinicians, and vascularization is considered as its determining factor. We previously accomplished pulp regeneration with autologous stem cells from deciduous teeth (SHED) aggregates implantation in teenager patients, however, the underlying mechanism needs to be clarified for regenerating pulp in adults. Serving as an important effector of mesenchymal stem cells (MSCs), exosomes have been reported to promote angiogenesis and tissue regeneration effectively. Here, we aimed to investigate the role of SHED aggregate-derived exosomes (SA-Exo) in the angiogenesis of pulp regeneration. We extracted exosomes from SHED aggregates and utilized them in the pulp regeneration animal model. The pro-angiogenetic effects of SA-Exo on SHED and human umbilical vein endothelial cells (HUVECs) were evaluated. The related mechanisms were further investigated. We firstly found that SA-Exo significantly improved pulp tissue regeneration and angiogenesis in vivo. Next, we found that SA-Exo promoted SHED endothelial differentiation and enhanced the angiogenic ability of HUVECs, as indicated by the in vitro tube formation assay. Mechanistically, miR-26a, which is enriched in SA-Exo, improved angiogenesis both in SHED and HUVECs via regulating TGF-β/SMAD2/3 signalling. In summary, these data reveal that SA-Exo shuttled miR-26a promotes angiogenesis via TGF-β/SMAD2/3 signalling contributing to SHED aggregate-based pulp tissue regeneration. These novel insights into SA-Exo may facilitate the development of new strategies for pulp regeneration.

Cell Proliferation published new progress about Angiogenesis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Formula: C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Tang, Junling; Hu, Peng; Zhou, Shixia; Zhou, Tiejun; Li, Xiaoming; Zhang, Li published the artcile< Lymphoma cell-derived extracellular vesicles inhibit autophagy and apoptosis to promote lymphoma cell growth via the microRNA-106a/Beclin1 axis>, Computed Properties of 6823-69-4, the main research area is lymphoma cell growth microRNA Beclin EV autophagy apoptosis; Beclin1; Lymphoma cells; apoptosis; autophagy; extracellular vesicles; microRNA-106a.

Lymphoma is a common malignant tumor globally. Tumor-derived extracellular vesicles (Evs) participate in genetic information exchange between tumor cells. We investigated the role and mechanism of human Burkitt lymphoma cells Raji-derived Evs (Raji-Evs) in lymphoma cells. Effects of Evs on lymphoma cell proliferation, invasion, autophagy, and apoptosis were assessed using Cell Counting Kit-8 method, Transwell assay, laser confocal microscopy, Western blotting, and flow cytometry. microRNA (miR)-106a expression in lymphoma cells was determined using reverse transcription-quant. polymerase chain reaction and then downregulated in Raji cells and then Evs were isolated (Evs-in-miR-106a) to evaluate its role in lymphoma cell growth. The binding relationship between miR-106a and Beclin1 was verified using RNA pull-down and dual-luciferase assays. Beclin1 was overexpressed in SU-DHL-4 and Farage cells and SU-DHL-4 cell autophagy and apoptosis were detected. The levels of miR-106a and Beclin1 in SU-DHL-4 cells were detected after adding autophagy inhibitors. The tumorigenicity assay in nude mice was performed to validate the effects of Raji-Evs in vivo. Raji-Evs promoted lymphoma cell proliferation and invasion and increased miR-106a. miR-106a knockdown reversed Evs-promoted lymphoma cell proliferation and invasion. miR-106a carried by Raji-Evs targeted Beclin1 expression. Beclin1 overexpression or miR-106a inhibitor reversed the effects of Evs on lymphoma cell autophagy and apoptosis. Autophagy inhibitors elevated miR-106a expression and lowered Beclin1 expression. Raji-Evs-carried miR-106a inhibited Beclin1-dependent autophagy and apoptosis in lymphoma cells, which were further verified in vivo, together with promoted tumor growth. We proved that Raji-Evs inhibited lymphoma cell autophagy and apoptosis and promoted cell growth via the miR-106a/Beclin1 axis.

Cell Cycle published new progress about Apoptosis. 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

Liu, Hanxiao; Wang, Xinxing; Chen, Lu; Chen, Liang; Tsirka, Stella E.; Ge, Shaoyu; Xiong, Qiaojie published the artcile< Microglia modulate stable wakefulness via the thalamic reticular nucleus in mice>, Application In Synthesis of 6823-69-4, the main research area is microglia stable wakefulness thalamic reticular nucleus.

Microglia are important for brain homeostasis and immunity, but their role in regulating vigilance remains unclear. We employed genetic, physiol., and metabolomic methods to examine microglial involvement in the regulation of wakefulness and sleep. Microglial depletion decreased stable nighttime wakefulness in mice by increasing transitions between wakefulness and non-rapid eye movement (NREM) sleep. Metabolomic anal. revealed that the sleep-wake behavior closely correlated with diurnal variation of the brain ceramide, which disappeared in microglia-depleted mice. Ceramide preferentially influenced microglia in the thalamic reticular nucleus (TRN), and local depletion of TRN microglia produced similar impaired wakefulness. Chemogenetic manipulations of anterior TRN neurons showed that they regulated transitions between wakefulness and NREM sleep. Their firing capacity was suppressed by both microglial depletion and added ceramide. In microglia-depleted mice, activating anterior TRN neurons or inhibiting ceramide production both restored stable wakefulness. These findings demonstrate that microglia can modulate stable wakefulness through anterior TRN neurons via ceramide signaling.

Nature Communications 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, Application In Synthesis of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Li, Minshu; Li, Xiuping; Wang, Dan; Gao, Xiaolin; Li, Shiyao; Cheng, Xiaojing; Shen, Yiming; Li, Shenghui; Jia, Qiang; Liu, Qiang published the artcile< Inhibition of exosome release augments neuroinflammation following intracerebral hemorrhage>, Application In Synthesis of 6823-69-4, the main research area is intracerebral hemorrhage neuroinflammation exosome; exosome; immunity; intracerebral hemorrhage; neuroinflammation.

Intracerebral hemorrhage (ICH) is a severe stroke subtype without effective pharmacol. treatment. Following ICH, peripheral leukocytes infiltrate into the brain and contribute to neuroinflammation and brain edema. However, the intercellular machinery controlling the initiation and propagation of leukocyte infiltration remains elusive. Exosomes are small extracellular vesicles released from donor cells and bridge intercellular communication. In this study, we investigated the effects of inhibition of exosome release on neuroinflammation and ICH injury. Using a mouse model of ICH induced by collagenase injection, we found that ICH induced an increase of exosome level in the brain. Inhibition of exosome release using GW4869 augmented neurol. deficits and brain edema after ICH. The exacerbation of ICH injury was accompanied by increased barrier disruption and brain infiltration of leukocytes. The detrimental effects of GW4869 were ablated in ICH mice receiving antibody depletion of Gr-1+ myeloid cells. Extracted exosomes from the ICH brains suppressed the production of inflammatory factors by splenocytes. Addnl., exosomes extracted from brain tissues of donor ICH mice reduced ICH injury in recipient mice. These results demonstrate that inhibition of exosome release augments neuroinflammation and ICH injury. The impact of exosomes released from the ICH brain on the immune system deserves further investigation.

FASEB Journal published new progress about Brain. 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

Wu, Yunfei; Li, Jun; Yuan, Rui; Deng, Zihui; Wu, Xu published the artcile< Bone marrow mesenchymal stem cell-derived exosomes alleviate hyperoxia-induced lung injury via the manipulation of microRNA-425>, Quality Control of 6823-69-4, the main research area is microRNA425 PTEN TSG101 CD34 GW4869 hyperoxia induced lung injury; Bone marrow mesenchymal stem cell-derived exosomes; Hyperoxia-induced lung injury; PI3K/AKT signaling Pathway; PTEN; microRNA-425.

Hyperoxia-induced lung injury (HILI) is an acute lung injury (LI) induced by extended periods of exposure to hyperoxia. Alleviating LI by bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) and microRNAs (miRs) has been previously reported. This study is devised to probe the interaction between BMSCs-Exos and miR-425 in HILI. Firstly, BMSCs-Exos were isolated and identified. Then, HILI rat models and RLE-6TN cell models were successfully established and treated by BMSCs-Exos. Afterwards, functional assays were conducted to explore cell biol. behaviors in models, with miR-425 expression detected. Then, the target relation between miR-425 and PTEN was clarified by luciferase reporter assay. Eventually, expression of PTEN and the PI3K/Akt axis was assessed by Western blotting and qRT-PCR. BMSCs-Exos promoted miR-425 expression and attenuated HILI and H2O2 induced RLE-6TN cell injury as evidence by alleviated lung cell injury, decreased TUNEL-pos. cells, induced cell viability and declined apoptosis (all p < 0.05). Besides, when miR-425 was knocked-down, the protective role of BMSCs-Exos in HILI was also reduced (all p < 0.05). miR-425 targeted PTEN mRNA, whose upregulation reversed the protective role of BMSCs-Exos in HILI (all p < 0.05). BMSCs-Exos improved the quenched levels of the PI3K/AKT axis in HILI (all p < 0.05). Our data supported that miR-425 in BMSCs-Exos inhibits HILI by targeting PTEN and upregulating the PI3K/AKT axis. This study may provide personalized interventions for HILI remedy. Archives of Biochemistry and Biophysics published new progress about Adipogenesis. 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

Deng, Chun-Lei; Hu, Cheng-Biao; Ling, Sheng-Tao; Zhao, Na; Bao, Li-Hui; Zhou, Feng; Xiong, Ye-Cheng; Chen, Tao; Sui, Bing-Dong; Yu, Xiao-Rui; Hu, Cheng-Hu published the artcile< Photoreceptor protection by mesenchymal stem cell transplantation identifies exosomal MiR-21 as a therapeutic for retinal degeneration>, Application In Synthesis of 6823-69-4, the main research area is retinal degeneration mesenchymal stem cell transplantation MiR21 exosome.

Abstract: Photoreceptor apoptosis is recognized as one key pathogenesis of retinal degeneration, the counteraction of which represents a promising approach to safeguard visual function. Here, we discovered that intravitreal MSCT counteracted photoreceptor apoptosis and alleviated retinal morphol. and functional degeneration in a mouse model of photoreceptor loss induced by N-methyl-N-nitrosourea (MNU). Notably, therapeutic efficacy of MSCT and EXOT on MNU-induced retinal degeneration was long-lasting as photoreceptor preservance and retinal maintenance were detected even after 1-2 mo post to injection for only once. More importantly, using a natural occurring retinal degeneration model caused by a nonsense mutation of Phosphodiesterase 6b gene (Pde6bmut), we confirmed that MSCT and EXOT prevented photoreceptor loss and protected long-term retinal function. In deciphering therapeutic mechanisms regarding potential exosome-mediated communications, we identified that miR-21 critically maintained photoreceptor viability against MNU injury by targeting programmed cell death 4 (Pdcd4) and was transferred from MSC-derived exosomes in vivo for functional regulation. Further experiments revealed that miR-21 mediated therapeutic effects of EXOT on MNU-induced photoreceptor apoptosis and retinal dysfunction. These findings uncovered the efficacy and mechanism of MSCT-based photoreceptor protection, indicating exosomal miR-21 as a therapeutic for retinal degeneration.

Cell Death & Differentiation published new progress about Apoptosis. 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

Hu, Haifeng; Wang, Dong; Li, Lihong; Yin, Haiyang; He, Guoyu; Zhang, Yonghong published the artcile< Role of microRNA-335 carried by bone marrow mesenchymal stem cells-derived extracellular vesicles in bone fracture recovery>, Application In Synthesis of 6823-69-4, the main research area is microRNA335 mesenchymal stem cell extracellular vesicle bone fracture.

Mesenchymal stem cells (MSCs) have the potential to reduce healing time and treat nonunion in fracture patients. In this study, bone marrow MSCs-derived extracellular vesicles (B-EVs) were firstly extracted and identified. CD9-/- and normal mice were enrolled for the establishment of fracture models and then injected with B-EVs. Osteoblast differentiation and fracture recovery were estimated The levels of osteoblast-related genes were detected, and differentially expressed microRNAs (miRs) in B-EVs-treated normal fracture mice were screened and verified. The downstream mechanisms of miR were predicted and assessed. The loss-of functions of miR-335 in B-EV and gain-of-functions of VapB were performed in animal and cell experiments to evaluate their roles in bone fracture. Collectively, B-EVs promoted bone fracture recovery and osteoblast differentiation by releasing miR-335. miR-335 downregulation in B-EVs impaired B-EV functions in fracture recovery and osteoblast differentiation. miR-335 could target VapB, and VapB overexpression reversed the effects of B-EVs on osteoblast differentiation. B-EV treatment activated the Wnt/β-catenin pathway in fracture mice and osteoblasts-like cells. Taken together, the study suggested that B-EVs carry miR-335 to promote bone fracture recovery via VapB and the Wnt/β-catenin pathway. This study may offer insights into bone fracture treatment.

Cell Death & Disease published new progress about Angiogenesis. 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

Tong, Ying; Ye, Chao; Ren, Xing-Sheng; Qiu, Yun; Zang, Ying-Hao; Xiong, Xiao-Qing; Wang, Jue-Jin; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing published the artcile< Exosome-Mediated Transfer of ACE (Angiotensin-Converting Enzyme) From Adventitial Fibroblasts of Spontaneously Hypertensive Rats Promotes Vascular Smooth Muscle Cell Migration>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is ACE fibroblast exosome vascular smooth muscle cell migration hypertension; captopril; exosomes; fibroblasts; hypertension; vascular remodeling.

Migration of vascular smooth muscle cells (VSMCs) is pivotal for vascular remodeling in hypertension. Vascular adventitial fibroblasts (AFs) are important in the homeostasis of vascular structure. This study is designed to investigate the roles of AF exosomes (AFE) in VSMC migration and underling mechanism. Primary VSMCs and AFs were obtained from the aorta of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. VSMC migration was evaluated with Boyden chamber assay and wound healing assay. AFE from WKY rats and SHR were isolated and identified. AFE from SHR promoted but AFE from WKY rats had no significant effect on VSMC migration. The effects of AFE on VSMC migration were prevented by an exosome inhibitor GW4869, an AT1R (Ang II [angiotensin II] type 1 receptor) antagonist losartan, or an inhibitor of ACE (angiotensin-converting enzyme) captopril. ACE contents and activity were much higher in AFE from SHR than those from WKY rats. There were no significant difference in Ang II and AT1R mRNA and protein levels between AFE from SHR and AFE from WKY rats. AFE from SHR increased Ang II and ACE contents and ACE activity in VSMCs of WKY rats and SHR. The changes of Ang II contents and ACE activity were prevented by captopril. ACE knockdown in AFs reduced ACE contents and activity in AFE from SHR and inhibited AFE-induced migration of VSMCs of WKY rats and those of SHR. These results indicate that exosomes from AFs of SHR transfer ACE to VSMCs, which increases Ang II levels and activates AT1R in VSMCs and thereby promotes VSMC migration.

Hypertension 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, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Liu, Tao; Chen, Gang; Sun, Dawei; Lei, Minghui; Li, Yongqiang; Zhou, Changming; Li, Xiaodong; Xue, Wei; Wang, Hong; Liu, Chunjun; Xu, Jiang published the artcile< Exosomes containing miR-21 transfer the characteristic of cisplatin resistance by targeting PTEN and PDCD4 in oral squamous cell carcinoma>, Application In Synthesis of 6823-69-4, the main research area is exosome miR21 anticancer cisplatin resistance oral squamous cell carcinoma; cisplatin resistance; exosome; miR-21; oral squamous cell carcinoma.

Resistance to chemotherapy remains a major obstacle for the effective treatment of oral squamous cell carcinoma (OSCC). Evidence for the involvement of exosomes as important regulators of cisplatin chemoresistance in OSCC is still poorly understood. Our objective of this study was to explore the roles for exosomes in modulating key cellular pathways mediating response to chemotherapy. We first developed the cisplatin-resistant cell lines (HSC-3-R and SCC-9-R) and found that the conditioned media from cisplatin-resistant OSCC cells enhanced the chemoresistance of parental OSCC cell. The release of exosomes was blocked by inhibitor (GW4869) and exosomes were found to be involved in the chemoresistance of parental OSCC cell transferred from resistant cells. The exosomes derived from resistant cells and parental cells were isolated. Then, the isolated exosomes were characterized and quantified by electron microscopy, qNano anal., and western blot anal. Exosomes derived from cisplatin-resistant OSCC cells were found to enhance the chemoresistance of OSCC cell and decrease the DNA damage signaling in response to cisplatin. It was also found that exosomes derived from cisplatin-resistant OSCC cells transferred miR-21 to OSCC parental cells and induced cisplatin resistance by targeting phosphatase and tensin homolog and programmed cell death 4. Furthermore, the roles of cisplatin-resistant OSCC cells-derived exosomes in vivo were confirmed by s.c. xenograft mouse model.Collectively, the results suggest that exosomes released from cisplatin-resistant OSCC cells transmit miR-21 to induce cisplatin resistance of OSCC cells.

Acta Biochimica et Biophysica Sinica published new progress about Antitumor agents. 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