Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Xanthoangelol (XAG), a prenylated chalcone isolated from the Japanese herb Angelica keiskei Koidzumi, has been reported to exhibit antineoplastic properties. However, the specific anti‐tumor activity of XAG in human hepatocellular carcinoma (HCC), and the relevant mechanisms are not known. Herein, we evaluated the effect of XAG against HCC in vitro and in vivo. Although XAG treatment did not significantly reduce the viability of the Hep3B and Huh7 cell lines, it suppressed cell migration, invasion, and EMT. This anti‐metastatic effect of XAG was due to induction of autophagy, because treatment with the autophagy inhibitor 3‐methyadenine (3‐MA) or knockdown of the pro‐autophagy Beclin‐1 effectively abrogated the XAG‐induced suppression of metastasis. Mechanistically, XAG induced autophagy via activation of the AMPK/mTOR signaling pathway, and XAG treatment dramatically increased the expression of p‐AMPK while decreasing p‐mTOR expression. In addition, blocking AMPK/mTOR axis with compound C abrogated the autophagy‐mediated inhibition of metastasis. The murine model of HCC metastasis also showed that XAG effectively reduced the number of metastatic pulmonary nodules. Taken together, our results revealed that autophagy via the activation of AMPK/mTOR pathway is essential for the anti‐metastatic effect of XAG against HCC. These findings not only contribute to our understanding of the anti‐tumor activity of XAG but also provide a basis for its clinical application in HCC. Before this study, evidence of XAG on HCC was purely anecdotal; present study provides the first comprehensive assessments of XAG on HCC metastasis and investigates its underlying mechanism. Results suggest that XAG exerts anti‐metastatic properties against HCC through inducing autophagy which is mediated by the activation of AMPK/mTOR signaling pathway. This research extends our knowledge about the antineoplastic properties of XAG and suggests that induction autophagy may represent future treatment strategies for metastatic HCC.     

Potential Interaction of Plasmodium falciparum Hsp60 and Calpain

After invasion of red blood cells, malaria matures within the cell by degrading hemoglobin avidly. For enormous protein breakdown in trophozoite stage, many efficient and ordered proteolysis networks have been postulated and exploited. In this study, a potential interaction of a 60-kDa Plasmodium falciparum (Pf)-heat shock protein (Hsp60) and Pf-calpain, a cysteine protease, was explored. Pf-infected RBC was isolated and the endogenous Pf-Hsp60 and Pf-calpain were determined by western blot analysis and similar antigenicity of GroEL and Pf-Hsp60 was determined with anti-Pf-Hsp60. Potential interaction of Pf-calpain and Pf-Hsp60 was determined by immunoprecipitation and immunofluorescence assay. Mizoribine, a well-known inhibitor of Hsp60, attenuated both Pf-calpain enzyme activity as well as P. falciparum growth. The presented data suggest that the Pf-Hsp60 may function on Pf-calpain in a part of networks during malaria growth.     

Tongxinluo Protects against Hypertensive Kidney Injury in Spontaneously-Hypertensive Rats by Inhibiting Oxidative Stress and Activating Forkhead Box O1 Signaling

Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1) signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRs)and elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of α-smooth muscle actin, extracellular matrixprotein, transforming growth factor β1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-α and interleukin-6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional activation of FoxO1 signaling.     

Biologically Induced Deposition of Fine Suspended Particles by Filter-Feeding Bivalves in Land-Based Industrial Marine Aquaculture Wastewater

Industrial aquaculture wastewater contains large quantities of suspended particles that can be easily broken down physically. Introduction of macro-bio-filters, such as bivalve filter feeders, may offer the potential for treatment of fine suspended matter in industrial aquaculture wastewater. In this study, we employed two kinds of bivalve filter feeders, the Pacific oyster Crassostrea gigas and the blue mussel Mytilus galloprovincialis, to deposit suspended solids from marine fish aquaculture wastewater in flow-through systems. Results showed that the biodeposition rate of suspended particles by C. gigas (shell height: 8.67±0.99 cm) and M. galloprovincialis (shell height: 4.43±0.98 cm) was 77.84±7.77 and 6.37±0.67 mg ind⁻¹•d⁻¹, respectively. The total solid suspension (TSS) deposition rates of oyster and mussel treatments were 3.73±0.27 and 2.76±0.20 times higher than that of the control treatment without bivalves, respectively. The TSS deposition rates of bivalve treatments were significantly higher than the natural sedimentation rate of the control treatment (P<0.001). Furthermore, organic matter and C, N in the sediments of bivalve treatments were significantly lower than those in the sediments of the control (P<0.05). It was suggested that the filter feeders C. gigas and M. galloprovincialis had considerable potential to filter and accelerate the deposition of suspended particles from industrial aquaculture wastewater, and simultaneously yield value-added biological products.     

Diversity of Rhizosphere Soil Arbuscular Mycorrhizal Fungi in Various Soybean Cultivars under Different Continuous Cropping Regimes

Recent studies have shown that continuous cropping in soybean causes substantial changes to the microbial community in rhizosphere soil. In this study, we investigated the effects of continuous cropping for various time periods on the diversity of rhizosphere soil arbuscular mycorrhizal (AM) fungi in various soybean cultivars at the branching stage. The soybean cultivars Heinong 37 (an intermediate cultivar), Heinong 44 (a high-fat cultivar) and Heinong 48 (a high-protein cultivar) were seeded in a field and continuously cropped for two or three years. We analyzed the diversity of rhizosphere soil AM fungi of these soybean plants at the branching stage using morphological and denaturing gradient gel electrophoresis (DGGE) techniques. The clustering analysis of unweighted pair-group method with arithmetic averages (UPGMA) was then used to investigate the AM fungal community shifts. The results showed that increasing the number of years of continuous cropping can improve the colonization rate of AM fungi in different soybean cultivars at the branching stage. The dominant AM fungi in the experimental fields were Funneliformismosseae and Glomus spp. The number of years of continuous cropping and the soybean cultivar both had obvious effects on the diversity of AM fungi, which was consistent with the results of colonization rate analysis. This study establishes a basis for screening dominant AM fungi of soybean. In addition, the results of this study may be useful for the development of AM fungal inoculants.