CCL24 Protects Renal Function by Controlling Inflammation in Podocytes.

Diabetic nephropathy (DN) is one of the most lethal complications of diabetes mellitus with chronic inflammation. We have examined the role of the inflammatory chemokine CCL24 in DN. We observed that serum levels of CCL24 were significantly elevated in patients with DN. Not only that, the expression of CCL24 was significantly increased in the kidneys of DN mice. The kidney of DN mice showed increased renal fibrosis and inflammation. We characterized an in vitro podocyte cell model with high glucose. Western blot analysis showed that expression of CCL24 was significantly increased under high-glucose conditions. Stimulation with high glucose (35 mmol/L) resulted in an increase in CCL24 expression in the first 48 hours but changed little after 72 hours. Moreover, with glucose stimulation, the level of podocyte fibrosis gradually increased, the expression of the proinflammatory cytokine IL-1ß was upregulated, and the expression of the glucose transporter GLUT4, involved in the insulin signal regulation pathway, also increased. It is suggested that CCL24 is involved in the pathogenesis of DN. In order to study the specific role of CCL24 in this process, we used the CRISPR-Cas9 technique to knock out CCL24 expression in podocytes. Compared with the control group, the podocyte inflammatory response induced by high glucose after CCL24 knockout was significantly increased. These results suggest that CCL24 plays a role in the development of early DN by exerting an anti-inflammatory effect, at least, in podocytes.

TM7SF1, an important autophagy regulatory protein in mouse podocytes.

The autophagy, which can be regulated by lysosomal membrane proteins, plays a critical role in maintaining normal podocyte function. TM7SF1 is a novel lysosomal membrane protein, but its effect on autophagy is still unknown. This study aimed to identify the role of TM7SF1 in mouse podocyte (MPC5) autophagy. Interestingly, we detected an increase in LC3BII and SQSTM1/P62 in MPC5 through inhibiting TM7SF1, and which can be completely corrected after blocking the autolysosome degradation with chloroquine (CQ). Moreover, inhibition of TM7SF1 expression did not increase the mRNA level of SQSTM1/P62. Theses results suggested that inhibition of TM7SF1 led to impaired degradation of autophagy products, which manifest as an abnormal accumulation of LC3BII and SQSTM1/P62. Further studies showed that the downregulation of TM7SF1 resulted in a significant decrease in the number of acid lysosomes, which directly led to decreases in the number and function of autolysosomes. In conclusion, TM7SF1 is therefore essential for autolysosomes degradation pathway at the end of autophagy flow, and for the maintenance of podocyte function.

Axial Impact Load of a Concrete-Filled Steel Tubular Member with Axial Compression Considering the Creep Effect.

The dynamic loads acting on concrete-filled steel tubular members under axial impacts by rigid bodies were studied herein by FEM. The whole impact process was simulated and the time history of the impact load was obtained. The effects of eight factors on the axial impact load were studied; these factors were the impact speed, mass ratio, axial pressure ratio, steel ratio, slenderness ratio, concrete strength, impact position, and boundary conditions. Besides this, the effects of concrete creep on the impact load were also considered by changing the material parameters of the concrete. The results show that axial impact load changes with time as a triangle. The peak value of impact load increases and the impact resistance improves with the growth of the axial pressure ratio, steel ratio, slenderness ratio, and concrete strength after creep occurs. As the eccentricity of the axial impact acting on a concrete-filled steel tubular member increases, the peak value of the impact load decreases. The enhancement of constraints at both ends of the member can improve the impact resistance. The creep reduction coefficients for the peak axial impact load of a concrete-filled steel tubular member under axial compression and considering the creep effect over 6 months and 30 years are 0.60 and 0.55, respectively. A calculation formula for the peak value of impact load was suggested based on the existing formula, and its accuracy was proved by finite element calculation in this study.

Cytotoxic and Antitumor Effects of Curzerene from Curcuma longa.

Curzerene is a sesquiterpene and component used in oriental medicine. It was originally isolated from the traditional Chinese herbal medicine Curcuma rhizomes. In this study, anticancer activity of curzerene was examined in both in vitro and in vivo models. The result of the MTT assay showed that curzerene exhibited antiproliferative effects in SPC-A1 human lung adenocarcinoma cells in a time-dependent and dose-dependent manner. The anticancer IC50s were 403.8, 154.8, and 47.0 µM for 24, 48, and 72 hours, respectively. The flow cytometry analysis indicated curzerene arrested the cells in the G2/M cell cycle and promoted or induced apoptosis of SPC-A1 cells. The percentage of cells arrested in the G2/M phase increased from 9.26 % in the control group cells to 17.57 % in the cells treated with the highest dose (100 µM) of curzerene. Western blot and RT-PCR analysis demonstrated that curzerene induced the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Tumor growth was significantly inhibited in SPC-A1 cell-bearing nude mice by using curzerene (135 mg/kg daily), meanwhile, curzerene did not significantly affect body mass and the organs of the mice, which may indicate that curzerene has limited toxicity and side effects in vivo. In conclusion, curzerene could inhibit the proliferation of SPC-A1 human lung adenocarcinoma cells line in both in vitro and in vivo models. Focusing on its relationship with GSTA1, curzerene could induce the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Curzerene might be used as an anti-lung adenocarcinoma drug candidate compound for further development.