Gluconeogenic enzyme PCK1 supports S-adenosylmethionine biosynthesis and promotes H3K9me3 modification to suppress hepatocellular carcinoma progression.

Deciphering the crosstalk between metabolic reprogramming and epigenetic regulation is a promising strategy for cancer therapy. In this study, we discovered that the gluconeogenic enzyme PCK1 fueled the generation of S-adenosylmethionine (SAM) through the serine synthesis pathway. The methyltransferase SUV39H1 catalyzed SAM, which served as a methyl donor to support H3K9me3 modification, leading to the suppression of the oncogene S100A11. Mechanistically, PCK1 deficiency-induced oncogenic activation of S100A11 was due to its interaction with AKT1, which upregulated PI3K/AKT signaling. Intriguingly, the progression of hepatocellular carcinoma (HCC) driven by PCK1 deficiency was suppressed by SAM supplement or S100A11 KO in vivo and in vitro. These findings reveal the availability of the key metabolite SAM as a bridge connecting the gluconeogenic enzyme PCK1 and H3K9 trimethylation in attenuating HCC progression, thus suggesting a potential therapeutic strategy against HCC.

Echinacoside inhibits the proliferation, migration, invasion and angiogenesis of ovarian cancer cells through PI3K/AKT pathway.

Echinacoside is a group of natural compounds extracted from medicinal plants Cistanche and Echinacea, which has neuroprotective, antiaging, immunomodulatory and anticancer effects, but its specific role and mechanism in tumor remains partially unclear. To our knowledge, it was the first time to reported the effect of Echinacoside in ovarian cancer. Colony formation, TUNEL staining, Transwell and tube formation assays were conducted to analyze the proliferation, apoptosis, invasion and tube formation abilities of serous ovarian carcinoma cells (SKOV3 and OVCAR-3), respectively. The expressions of apoptosis-, invasion- and PI3K/AKT pathway-related proteins were measured by western blotting. In addition, PI3K agonist (740Y-P) was used to assess the regulatory effect of Echinacoside on PI3K/AKT signaling in ovarian cancer. Finally, the anti-tumor effect of Echinacoside on SKOV3-xenografted mice was evaluated by xenograft tumor mouse model. Our results demonstrated Echinacoside concentration-dependently reduced the proliferation, migration and angiogenesis of ovarian cancer cells, whereas promoted apoptosis. Moreover, western blotting revealed that Echinacoside suppressed the growth of ovarian cancer cells by downregulating the phosphorylation levels of PI3K, AKT and mTOR, which could be partially reversed by 740Y-P. Further, in vivo results showed that Echinacoside could effectively alleviate the tumor growth of xenograft mice, accompanied by the decrease of PI3K/AKT signaling. In general, our results demonstrate that Echinacoside could reduce the ovarian cancer progression through inhibition of PI3K/AKT pathway, suggesting that Echinacoside may be a new treatment option for ovarian cancer.

Identification, tissue distribution, and anorexigenic effect of amylin in Siberian sturgeon (Acipenser baeri).

Amylin is a 37-amino acid polypeptide that has been found to be involved in feeding regulation in some mammals, birds, and goldfish. We cloned amylin of Siberian sturgeon and detected its distribution pattern in 15 tissues. The expression levels in the periprandial period (pre-and post-feeding), the changes in the food intake, and the expression levels of related appetite factors after the intraperitoneal injection of amylin were detected. The expression of amylin was found to be the highest in the hypothalamus. Compared with 1 h pre-feeding, the expression levels of amylin in the hypothalamus and duodenum were increased significantly 1 h post-feeding. Compared with the control group (saline), intraperitoneal injection of 50 ng/g, 100 ng/g, and 200 ng/g of amylin significantly inhibited food intake at 1 h post injection, but not at 3 h and 6 h. The injection of 50 ng/g, 100 ng/g, and 200 ng/g amylin significantly inhibited the cumulative feed. After 1 h of 50 ng/g amylin injection, the levels of MC4R and somatostatin in the hypothalamus increased significantly, while the levels of amylin and NPY decreased significantly. The levels of CCK in the valvular intestine were increased significantly. Insulin in the duodenum was also increased significantly, but there was no significant change in ghrelin in the duodenum. These results show that amylin inhibits feeding in Siberian sturgeon by down-regulating the appetite-stimulating factor NPY and up-regulating the appetite-suppressing factors somatostatin, MC4R, CCK, and insulin. This study provides a theoretical basis for studying the feeding function and action mechanisms of amylin in Siberian sturgeon.

Identification, tissue distribution, periprandial expression, and anorexigenic effect of spexin in Siberian sturgeon, Acipenser baeri.

Spexin (Spx), an endogenous peptide, is considered to be a neuropeptide. In a few fish and mammals, it has been proved to play a role in the regulation of animal feeding. However, the possible mechanisms of spexin regulating food intake are mostly blurry in vertebrates including Siberian sturgeon. In this study, firstly, the coding sequence of spexin cDNA was cloned and sequenced in Siberian sturgeon. Then, we detected that spexin mRNA was widely expressed in the hypothalamus, gastrointestinal tract, and liver, with the highest expression in the hypothalamus. The expression of spexin mRNA in the hypothalamus was significantly increased after food intake. At 1 h, 3 h, and 6 h after injection, the food intake in the spexin group (0.10, 0.30, and 0.90 µg/g BW) was significantly lower than that in the saline group. Moreover, compared with the saline group, the mRNA expression of anorectic nucb2, cart, ucn3, and pyy in the hypothalamus was significantly upregulated and orectic npy was significantly downregulated at 1 h after spexin injection; in the stomach, the mRNA expression of nucb2 and pyy was significantly upregulated. All in all, these results provide evidence for the anorexic effect of spexin on Siberian sturgeon.

Transcriptome analysis and the effects of polyunsaturated fatty acids on the immune responses of the critically endangered angtze sturgeon (Acipenser dabryanus).

The poor understanding of nutrition needed has become a significant obstruction to artificial conservation of Yangtze sturgeon (Acipenser dabryanus) and the relationship between ployunsaturated fatty acid nutrition and the immune response of Yangtze sturgeon is remains unclear. To explore this relationship, the immune response was determined by the activities of serum immune-related enzymes and the transcriptome pattern in the spleen after feeding different fat source diets for 7 weeks. In addition, the gene expression pattern after a lipopolysaccharide (LPS) challenge was investigated in the presence of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Long-term feeding of the fish oil diets increased the serum immune-related enzyme activities, including lysozyme, acid phosphatase, and alkaline phosphatase of Yangtze sturgeon. More than 653,999 transcripts with an N50 length of 1047 bp were obtained and a final set of 280,408 unigenes was generated. After annotating the unigenes, 3549 genes were assigned to the immune system and 2839 were identified to participate in the response to the different fat sources. A transcriptome assay showed the fish oil diets moderately upregulated immune-related signaling pathways in the spleen of Yangtze sturgeon, including NLR signaling, platelet activation, Fc gamma R-mediated phagocytosis, Th17 cell differentiation, and Th1 and Th2 cell differentiation. The quantitative polymerase chain reaction (qPCR) results of candidate genes for these pathways showed similar results. The LPS challenge study revealed that DHA and EPA moderately upregulated the candidate immune-related genes and modulated excessive activation of the immune pathway by the pathogen. This study confirmed the immunomodulatory function of unsaturated fatty acids in Yangtze sturgeon. This research will provide a reference for the preparation of artificial diets for Yangtze sturgeon.

In Situ Selective Measurement of SeIV in Waters and Soils: Diffusive Gradients in Thin-Films with Bi-Functionalized Silica Nanoparticles.

The speciation of selenium (Se) controls its fate and behavior, determining both its biological and environmental activities. However, in situ monitoring of SeIV presents a significant challenge due to its sensitivity to redox change. A novel diffusive gradients in thin films (DGT) technique containing mercapto-, amino-bifunctionalized SBA15 mesoporous silica nanoparticles was developed and evaluated in a series of laboratory and field deployment tests. The SBA-DGT exhibited a linear accumulation of SeIV ( r2 > 0.997) over a 72 h deployment, with negligible accumulation of SeVI(<5%). Consistent prediction of SeIV occurred within ionic strength and pH ranges of 0.1-200 mmol L-1 and 3.6-8, respectively. Limits of detection of the SBA-DGT were 0.03 µg SeIV L-1, which is suitable for natural waters. Moreover, the properties of the bifunctionalized SBA15 enable it to be fabricated within ultrathin (0.05 mm) gel layers for use in conjunction with O2 planar optode imaging. This new sandwich sensor technology with SBA-DGT was validated by mapping the two-dimensional distribution of SeIV and oxygen simultaneously in rice rhizospheres. This study shows that SBA-DGT provides a selective measurement of SeIV in situ, demonstrating its potential for both environmental monitoring and as a research tool for improving our understanding of Se biogeochemical processes.

Phytate induced arsenic uptake and plant growth in arsenic-hyperaccumulator Pteris vittata.

Phytate is abundant in soils, which is stable and unavailable for plant uptake. However, it occurs in root exudates of As-hyperaccumulator Pteris vittata (PV). To elucidate its effect on As uptake and growth, P. vittata were grown on agar media (63 µM P) containing 50 µM As and/or 50 or 500 µM phytate with non As-hyperaccumulator Pteris ensiformis (PE) as a congeneric control for 60 d. Phytate induced efficient As and P uptake, and enhanced growth in PV, but had little effects on PE. The As concentrations in PV fronds and roots were 157 and 31 mg kg-1 in As50+phytate50, 2.2- and 3.1-fold that of As50 treatment. Phosphorus uptake by PV was reduced by 27% in As treatment than the control (P vs. P+As) but increased by 73% comparing phytate500 to phytate500+As, indicating that PV effectively took up P from phytate. Neither As nor phytate affected Fe accumulation in PV, but phytate reduced root Fe concentration in PE (46-56%). As such, the increased As and P and the unsuppressed Fe uptake in PV probably promoted PV growth. Thus, supplying phytate to As-contaminated soils may promote As uptake and growth in PV and its phytoremediation ability.

Characterization of gene expression regulated by American ginseng and ginsenoside Rg3 in human colorectal cancer cells.

American ginseng (Panax quinquefolius L., Araliaceae) possesses anti-cancer potential and is one of the most commonly used herbal medicines in the United States. Ginsenoside Rg3, one of the saponins in American ginseng, has been shown to inhibit tumor growth. In this study, we sought to characterize the downstream genes targeted by American ginseng extracts in HCT-116 human colorectal cancer cells. We first demonstrated that the content of Rg3 in American ginseng steamed at 120 degrees C for 2 h (referred to as S2h) was significantly increased when compared with that of the unsteamed ginseng. Both S2h and Rg3 exhibited antiproliferative effects on HCT-116 cells. Using the Affymetrix high density genechips containing more than 40,000 genes and ESTs, the gene expression profiling of HCT-116 cells were assayed. Microarray data indicated that the expression levels of 76 genes were changed significantly after treatment with S2h or Rg3, whereby it was found that 52 of the 76 genes were up-regulated while the remaining 24 were down-regulated. Ingenuity pathways analysis of top functions affected by both S2h and Rg3 were carried out. The most effected pathway is the Ephrin receptor pathway. To validate the microarray data, quantitative real-time PCR of six candidate target genes was conducted, whereby it was found that three genes were up-regulated (AKAPA8L, PMPCB and PDE5A) and three were down-regulated (PITPNA, DUS2L and RIC8A). Although further studies are needed to elucidate the mechanisms of action, our findings should expand the understanding of the molecular framework of American ginseng as an anti-cancer agent.