TRAF Family Member 4 Promotes Cardiac Hypertrophy Through the Activation of the AKT Pathway.

Background Pathological cardiac hypertrophy is a major cause of heart failure morbidity. The complex mechanism of intermolecular interactions underlying the pathogenesis of cardiac hypertrophy has led to a lack of development and application of therapeutic methods. Methods and Results Our study provides the first evidence that TRAF4, a member of the tumor necrosis factor receptor-associated factor (TRAF) family, acts as a promoter of cardiac hypertrophy. Here, Western blotting assays demonstrated that TRAF4 is upregulated in cardiac hypertrophy. Additionally, TRAF4 deletion inhibits the development of cardiac hypertrophy in a mouse model after transverse aortic constriction surgery, whereas its overexpression promotes phenylephrine stimulation-induced cardiomyocyte hypertrophy in primary neonatal rat cardiomyocytes. Mechanistically, RNA-seq analysis revealed that TRAF4 promoted the activation of the protein kinase B pathway during cardiac hypertrophy. Moreover, we found that inhibition of protein kinase B phosphorylation rescued the aggravated cardiomyocyte hypertrophic phenotypes caused by TRAF4 overexpression in phenylephrine-treated neonatal rat cardiomyocytes, suggesting that TRAF4 may regulate cardiac hypertrophy in a protein kinase B-dependent manner. Conclusions Our results revealed the regulatory function of TRAF4 in cardiac hypertrophy, which may provide new insights into developing therapeutic and preventive targets for this disease.

Salidroside suppresses proliferation and migration in prostate cancer via the PI3K/AKT pathway.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies in men. PCa is difficult to detect in its early stages, and most patients are diagnosed in the middle to late stages. At present, drug therapy for advanced PCa is still insufficient. Some patients develop drug resistance in the later stage of therapy, which leads to tumor recurrence, metastasis and even treatment failure. Therefore, it is crucial to find new and effective drugs to treat prostate cancer. OBJECTIVE: The aim of this study was to investigate the anti-cancer effect of salidroside, an active ingredient in a traditional Chinese herbal medicine, on PCa. METHODS: Two human PCa cell lines, PC3 and DU145, were cultured and treated with salidroside. Cell viability and proliferation ability were analyzed through CCK-8 and colony assays, and cell migration ability was detected by Transwell and Scratch assays. RT-PCR and WB were used to detected the expression levels of moleculars related to cell proliferation, apoptosis, migration, and AKT signaling pathway. Forthmore, we performed rescue experiments with agonist to verify the affected signaling pathway. RESULTS: Salidroside inhibited the proliferation, colony formation, and migration of PCa cells. Meanwhile, apoptosis of PCa cells was enhanced. Moreover, salidroside inhibited PI3K/AKT pathway in PCa cells. The treatment of AKT agonist 740Y-P abrogated the inhibitory effect of salidroside on the PI3K/AKT signaling pathway. CONCLUSIONS: Our study demonstrated that in PCa cells, salidroside inhibites proliferation and migration and promots apoptosis via inhibiting PI3K/AKT pathway.

Carnosol inhibits cerebral ischemia-reperfusion injury by promoting AMPK activation.

BACKGROUND: Carnosol is a phytopolyphenol (diterpene) found and extracted from plants of Mediterranean diet, which has anti-tumor, anti-inflammatory and antioxidant effects. However, its role in ischemic stroke has not been elucidated. METHODS: Primary neurons subjected to oxygen-glucose deprivation (OGD) was used to investigate the effect of carnosol in vitro. A mouse MCAO model was used to evaluate the effect of carnosol on ischemic stroke in vivo. The mRNA level of inflammatory and apoptosis-related genes was determined by RT-PCR. The protein level of total and phosphorylated AMPK was determined by WB. H&E and Immunofluorescent assay was used to investigate the necrosis, inflammation and apoptosis in brain tissue. RESULTS: Carnosol protected the activity of primary neurons subjected to oxygen-glucose deprivation (OGD) in vitro, as well as inhibited inflammation and apoptosis. Furthermore, carnosol could significantly reduce the infarct and edema volume and protect against neurological deficit in vivo, and had a significant inhibitory effect on brain neuroinflammation and apoptosis. Mechanically, carnosol could activate AMPK, and the effect of carnosol on cerebral ischemia-reperfusion injury cell model could be abolished by AMPK phosphorylation inhibitor. CONCLUSION: Carnosol has a protective effect on ischemic stroke, and this effect is achieved through AMPK activation. Our study demonstrates the protective effect of carnosol on cerebral ischemia-reperfusion injury and provides a new perspective for the clinical treatment of ischemic stroke.

E3 ubiquitin ligase RNF5 attenuates pathological cardiac hypertrophy through STING.

Ring-finger protein 5 (RNF5) is an E3 ubiquitin ligase which is expressed in a variety of human tissues. RNF5 is involved in the regulation of endoplasmic reticulum stress, inflammation, and innate immunity and plays an important role in the occurrence and development of various tumors. However, the role of RNF5 in cardiac hypertrophy has not been reported. In this study, we found the expression of RNF5 was increased in the hearts of mice with pathological cardiac hypertrophy. The loss-of-function research demonstrated that RNF5 deficiency exacerbated cardiac hypertrophy, whereas gain-of-function studies revealed that overexpression of RNF5 had opposite effects. The stimulator of interferon genes (STING) is a signaling molecule that can activate type I interferon immunity, which can meditate inflammation and immune response in many diseases. The protein-protein interaction experiments confirmed that STING interacted with RNF5. Further studies showed that RNF5 inhibited cardiac hypertrophy by promoting STING degradation through K48-linked polyubiquitination. Therefore, we defined RNF5 as importantly regulated signaling for cardiac hypertrophy.

Determination and Pharmacokinetic Comparisons of Atractylodin after Oral Administration of Crude and Processed Atractylodis rhizoma.

BACKGROUND: In traditional Chinese medicine, Atractylodis rhizoma is the dried rhizome of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz. After being processed, the dryness of A. rhizoma decreased, and the function of tonifying spleen increased. Therefore, the processed A. rhizoma is the best choice of clinical application. As the main active components, polyethylene alkynes exhibits various desirable pharmacological effects including anti-inflammatory, anti-bacterial and anti-arrhythmia activity. However, there is no report on the pharmacokinetic comparisons of atractylodin, one of polyethylene alkynes, in bio-samples after oral administration of crude and processed A. rhizoma until now. The in vivo study of active components of A. rhizoma would be necessary and helpful for clinical application and clarification of processing principle. OBJECTIVE: To compare the pharmacokinetic parameters of atractylodin after oral administration of crude and processed A. rhizoma, and clarify the processing principle of A. rhizoma. MATERIALS AND METHODS: Plasma concentrations of atractylodin in rats were determined by reversed-phase high-performance liquid chromatogram and the main pharmacokinetic parameters were estimated with Drug and Statistics 2.0 Software Package (Chinese Pharmacological Society, Shanghai, China). RESULTS: The AUC0-t, AUC0→∞, Tmax, and Cmax of processed A. rhizoma were increased significantly (P < 0.05) compared with that in crude A. rhizoma after using Student's t-test. CONCLUSIONS: Processing A. rhizoma with wheat bran by stir-frying can promote and accelerate the absorption of atractylodin. SUMMARY: In this paper, a RP-HPLC method with UV detection for quantification of atractylodin (a main active component in Atractylodis Rhizoma) in rat plasma has been developed and applied to a preliminary pharmacokinetic study of atractylodin after oral administration of crude and processed Atractylodis Rhizoma respectively. The result indicates that processing Atractylodis Rhizoma with wheat-bran can promote and accelerate the absorption of atractylodin.

Multicolor emission from large-area porous thin films constructed of nanowires of small organic molecules.

We describe a facile low-temperature physical vapor deposition approach to fabricate porous network thin films constructed of nanowires of small organic molecules on a large area. Supermolecular assemblies of pyrene nanowires based on a combination of van der Waals forces and pi-pi stacking tend to hierarchically self-assemble to form uniform porous films using our techniques. The morphology of the films is studied and we also study several reasons influencing the process of assembly such as evaporation temperature, deposition temperature, and different kinds of substrate. The deposition temperature is determined to be the main reason for hierarchical aggregation. Typically prepared films exhibit unique optical properties, that is, multicolor red-green-blue emissions. This novel method can be applied to other organic molecular systems and may be potentially used to place nanoscaled building blocks directly on solid surfaces for fabricating large-area nanostructure-based flat screens.