Category: 6823-69-4

Lu, Zhongyang; Li, Yanchun; Syn, Wing-Kin; Wang, Zhewu; Lopes-Virella, Maria F.; Lyons, Timothy J.; Huang, Yan published the artcile< Amitriptyline inhibits nonalcoholic steatohepatitis and atherosclerosis induced by high-fat diet and LPS through modulation of sphingolipid metabolism>, Reference of 6823-69-4, the main research area is atherosclerosis nonalcoholic steatohepatitis amitriptyline antiatherosclerotic sphingolipid; acid sphingomyelinase; amitriptyline; diabetes; inflammation; nonalcoholic steatohepatitis.

We reported previously that increased acid sphingomyelinase (ASMase)-catalyzed hydrolysis of sphingomyelin, which leads to increases in ceramide and sphingosine 1 phosphate, played a key role in the synergistic upregulation of proinflammatory cytokines by palmitic acid (PA), a major saturated fatty acid, and lipopolysaccharide (LPS) in macrophages. Since macrophages are vital players in nonalcoholic steatohepatitis (NASH) and atherosclerosis, we assessed the effect of ASMase inhibition on NASH and atherosclerosis cooperatively induced by high-PA-containing high-fat diet (HP-HFD) and LPS in LDL receptor-deficient mice. Interestingly, immunohistochem. study showed that amitriptyline, but not GW4869, strongly reduced hepatic inflammation. Furthermore, results showed that both amitriptyline and GW4869 attenuated atherosclerosis. To elucidate the underlying mechanisms whereby amitriptyline inhibited both NASH and atherosclerosis, but GW4869 only inhibited atherosclerosis, we found that amitriptyline, but not GW4869, downregulated proinflammatory cytokines in macrophages. Finally, we found that inhibition of sphingosine 1 phosphate production is a potential mechanism whereby amitriptyline inhibited proinflammatory cytokines. Collectively, this study showed that amitriptyline inhibited NASH and atherosclerosis through modulation of sphingolipid metabolism in LDLR-/- mice, indicating that sphingolipid metabolism in macrophages plays a crucial role in the linkage of NASH and atherosclerosis.

American Journal of Physiology published new progress about Atherosclerosis. 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

Ren, Jing; Ding, Liang; Zhang, Dongya; Shi, Guoping; Xu, Qianyun; Shen, Sunan; Wang, Yaping; Wang, Tingting; Hou, Yayi published the artcile< Carcinoma-associated fibroblasts promote the stemness and chemoresistance of colorectal cancer by transferring exosomal lncRNA H19>, Electric Literature of 6823-69-4, the main research area is colorectal cancer fibroblast stemness chemoresistance lncRNA H19; CAFs; CRC; H19; chemoresistance; stemness.

In this study, we further investigated the underlying tumor-promoting roles of CAFs and the mol. mediators involved in these processes. Methods: The AOM/DSS-induced colitis-associated cancer (CAC) mouse model was established, and RNA sequencing was performed. SW480 cells with H19 stably knocked down were used to establish a xenograft model. The indicated protein levels in xenograft tumor tissues were confirmed by immunohistochem. assay, and cell apoptosis was analyzed by TUNEL apoptosis assay. The AldeRed ALDH detection assay was performed to detect intracellular aldehyde dehydrogenase (ALDH) enzyme activity. Results: H19 was highly expressed in the tumor tissues of CAC mice compared with the expression in normal colon tissues. Moreover, H19 was associated with the stemness of colorectal cancer stem cells (CSCs) in CRC specimens. Of note, H19 was enriched in CAF-derived conditioned medium and exosomes, which in turn promoted the stemness of CSCs and the chemoresistance of CRC cells in vitro and in vivo. Conclusion: CAFs promote the stemness and chemoresistance of CRC by transferring exosomal H19. H19 activated the β-catenin pathway via acting as a competing endogenous RNA sponge for miR-141, while miR-141 inhibited the stemness of CRC cells. Our findings indicate that H19 expressed by CAFs of the colorectal tumor stroma contributes to tumor development and chemoresistance.

Theranostics published new progress about Animal gene, HSP70 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Essandoh, Kobina; Yang, Liwang; Wang, Xiaohong; Huang, Wei; Qin, Dongze; Hao, Jiukuan; Wang, Yigang; Zingarelli, Basilia; Peng, Tianqing; Fan, Guo-Chang published the artcile< Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction>, Reference of 6823-69-4, the main research area is GW4869 exosome sepsis inflammation cardiac dysfunction; Cardiac dysfunction; Exosomes; Inflammatory response; Macrophages; Sepsis.

Sepsis is an infection-induced severe inflammatory disorder that leads to multiple organ failure. Amongst organs affected, myocardial depression is believed to be a major contributor to septic death. While it has been identified that large amounts of circulating pro-inflammatory cytokines are culprit for triggering cardiac dysfunction in sepsis, the underlying mechanisms remain obscure. Addnl., recent studies have shown that exosomes released from bacteria-infected macrophages are pro-inflammatory. Hence, we examined in this study whether blocking the generation of exosomes would be protective against sepsis-induced inflammatory response and cardiac dysfunction. To this end, we pre-treated RAW264.7 macrophages with GW4869, an inhibitor of exosome biogenesis/release, followed by endotoxin (LPS) challenge. In vivo, we injected wild-type (WT) mice with GW4869 for 1 h prior to endotoxin treatment or cecal ligation/puncture (CLP) surgery. We observed that pre-treatment with GW4869 significantly impaired release of both exosomes and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in RAW264.7 macrophages. At 12 h after LPS treatment or CLP surgery, WT mice pre-treated with GW4869 displayed lower amounts of exosomes and pro-inflammatory cytokines in the serum than control PBS-injected mice. Accordingly, GW4869 treatment diminished the sepsis-induced cardiac inflammation, attenuated myocardial depression and prolonged survival. Together, our findings indicate that blockade of exosome generation in sepsis dampens the sepsis-triggered inflammatory response and thereby, improves cardiac function and survival.

Biochimica et Biophysica Acta, Molecular Basis of Disease published new progress about Bacterial infection. 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