Trend Of Decreased Expression Research Articles

The Flavoring Agent Ethyl Vanillin Induces Cellular Stress Responses in HK-2 Cells.

Flavored e-cigarettes are a popular alternative to cigarette smoking; unfortunately, the extrapulmonary effects are not well-characterized. Human proximal tubule cells were cultured for 24 or 48 h with 0-1000 µM ethyl vanillin (ETH VAN) and cytotoxicity evaluated. Mitochondrial health was significantly diminished following 48 h of exposure, accompanied by significantly decreased spare capacity, coupling efficiency, and ATP synthase expression. ETH VAN at 24 h inhibited glycolysis. The endoplasmic reticulum (ER) stress marker C/EBP homologous protein (CHOP) was increased at 100 μM relative to 500-1000 μM. The downstream proapoptotic marker cleaved caspase-3 subsequently showed a decreasing trend in expression after 48 h of exposure. The autophagy biomarkers microtubule-associated proteins 1A/1B light chain 3 (LC3B-I and LC3B-II) were measured by Western blot. LC3B-II levels and the LC3B-II/LC3B-I ratio increased at 24 h, which suggested activation of autophagy. In contrast, by 48 h, the autophagy biomarker LC3B-II decreased, resulting in no change in the LC3B-II/LC3B-I ratio. Mitophagy biomarker PTEN-induced putative kinase 1 (PINK1) expression decreased after 48 h of exposure. The downstream marker Parkin was not significantly changed after 24 or 48 h. These findings indicate that the flavoring ETH VAN can induce energy pathway dysfunction and cellular stress responses in a renal model.

Three novel trehalase genes from Harmonia axyridis (Coleoptera: Coccinellidae): cloning and regulation in response to rapid cold and re-warming

Trehalose is the main blood sugar in insects. To study the function of trehalase during exposure to low temperatures, three other novel cDNAs of trehalase were cloned from Harmonia axyridis by transcriptome sequencing and rapid amplification of cDNA ends. One of the cloned cDNAs encoded a soluble trehalase, the second trehalase cDNA encoded a transmembrane-like domain, and the third cDNA encoded a membrane-bound protein. Therefore, these cDNAs were, respectively, named HaTreh1-5, HaTreh2-like, and HaTreh2. HaTreh1-5, HaTreh2-like, and HaTreh2 cDNAs encoded proteins containing 586, 553, and 633 amino acids with predicted masses of approximately 69.47, 63.46, and 73.66 kDa, and pIs of 9.20, 5.52, and 6.31, respectively. All three novel trehalases contained signal motifs “PGGINKESYYLDSY”, “QWDYPNAWPP”, and a highly conserved glycine-rich (GGGGEY) region. The expression levels of HaTreh1-5 and HaTreh2 mRNAs were high during adult stages, whereas HaTreh2-like was expressed in low amounts in the fourth larval stage. The results showed that the activity of membrane-bound trehalases decreased from 25 to 10 °C and from 5 to − 5 °C during cooling. The results also revealed a decreasing trend in expression of the three HaTreh mRNAs during the cooling treatment, and an initial decrease followed by an increase during the process of re-warming.

Renoprotective effects of novel interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 through anti-inflammatory action in 5/6 nephrectomized rats.

Renal inflammation is a final common pathway of chronic kidney disease (CKD), and its progression can be used to effectively gauge the degree of renal dysfunction. Interleukin-1 (IL-1) receptor-associated kinase 4 (IRAK-4) has been reported to be a pivotal molecule for IL-1 receptor- and Toll-like receptor-induced signaling and activation of proinflammatory mediators. In this study, we hypothesized that if inflammation plays a key role in renal failure, then the anti-inflammatory effect of IRAK-4 inhibitor should be effective in improving CKD. To determine its pharmacological potency, we investigated the renoprotective properties of the novel IRAK-4 inhibitor AS2444697 (N-[3-carbamoyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-2-(2-methylpyridin-4-yl)-1,3-oxazole-4-carboxamide hydrochloride (1:1)) in 5/6 nephrectomized (Nx) rats, a model of CKD. Six weeks' repeated administration of AS2444697 (0.3-3mg/kg, twice daily) dose-dependently and significantly reduced urinary protein excretion and prevented the development of glomerulosclerosis and interstitial fibrosis without affecting the blood pressure. In addition, AS2444697 showed beneficial effects on renal function as demonstrated by the decrease in levels of plasma creatinine and blood urea nitrogen and attenuation of decline in creatinine clearance. 5/6 Nx rats exhibited low-grade inflammation as evidenced by increased renal mRNA expression and plasma levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α, and MCP-1) and C-reactive protein as a marker of systemic inflammation. AS2444697 significantly reduced or showed a decreasing trend in expression and levels of these inflammatory parameters. These results suggest that AS2444697 suppresses the progression of chronic renal failure via anti-inflammatory action and may therefore be potentially useful in treating CKD patients.