Full-length transcriptome analysis reveals the mechanism of acupuncture at PC6 improves cardiac function in myocardial ischemia model.

BACKGROUND: The pathological process of myocardial ischemia (MI) is very complicated. Acupuncture at PC6 has been proved to be effective against MI injury, but the mechanism remains unclear. This study investigated the mechanism that underlies the effect of acupuncture on MI through full-length transcriptome. METHODS: Adult male C57/BL6 mice were randomly divided into control, MI, and PC6 groups. Mice in MI and PC6 group generated MI model by ligating the left anterior descending (LAD) coronary artery. The samples were collected 5 days after acupuncture treatment. RESULTS: The results showed that treatment by acupuncture improved cardiac function, decreased myocardial infraction area, and reduced the levels of cTnT and cTnI. Based on full-length transcriptome sequencing, 5083 differential expression genes (DEGs) and 324 DEGs were identified in the MI group and PC6 group, respectively. These genes regulated by acupuncture were mainly enriched in the inflammatory response pathway. Alternative splicing (AS) is a post-transcriptional action that contributes to the diversity of protein. In all samples, 8237 AS events associated with 1994 genes were found. Some differential AS-involved genes were enriched in the pathway related to heart disease. We also identified 602 new genes, 4 of which may the novel targets of acupuncture in MI. CONCLUSIONS: Our findings suggest that the effect of acupuncture on MI may be based on the multi-level regulation of the transcriptome.

Total Flavonoid Extract from Abelmoschus manihot (L.) Medic Flowers Attenuates d-Galactose-Induced Oxidative Stress in Mouse Liver Through the Nrf2 Pathway.

Abelmoschus manihot (L.) Medic is an edible hibiscus that is rich in flavonoids, and its use as Chinese herbal medicine for the treatment of diseases and health maintenance dates back to ancient times. The chemical compositions of total flavonoid of A. manihot (L.) Medic flower extract (TFAE) were identified and determined by high performance liquid chromatography (HPLC). The effects of TFAE on antioxidative activities in a d-galactose (d-gal)-induced mouse model and Nrf2-mediated antioxidant responses were evaluated. Male Kunming mice were randomly divided into normal control group, d-gal aging model group, d-gal+ascorbic acid group that served as a positive control, and d-gal+TFAE (40, 80, and 160 mg TFAE/kg) group. After 42 days, the antioxidant effects of these treatments were determined by biochemical studies, Western blotting, quantitative real-time polymerase chain reaction, and histological analysis. The results showed that the groups administered TFAE exhibited significant elevation in liver activities of antioxidant enzymes, including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), and decreased malondialdehyde (MDA) production in a dose-dependent manner compared with the d-gal-induced model group. Expression of Nrf2 and its target antioxidants (HO-1 and NQO1) was manifestly increased by TFAE treatment. TFAE also increased mRNA expression of GPx, SOD, and CAT and decreased tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). Furthermore, the microstructure of livers in TFAE-administered mice was obviously improved as compared with the d-gal model group. These results suggest that TFAE protects mice against d-gal-induced oxidative stress, and the effect is related to the activation of Nrf2 signaling.

[Effects of Hydrothermal Treatment Time on the Transformations of N, P, K and Heavy Metals in Sewage Sludge].

Hydrothermal treatment (HTT) of sewage sludge was conducted, focusing on the influence of HTT time on the dewaterability of sludge and transformations of elements N, P, K and heavy metals. The results showed that at a hydrotherma temperature of 160°C, with HTT time increasing from 30 to 120 min, the sludge dewatering performance was significantly improved. The transfer rate of N element in the sludge transferring to aqueous product increased gradually. Almost all of P element remained in the solid phase, and most of K element (57%-62%) was still in the solid phase although it was more easily transferred to the liquid phase than P element. The transferring behavior of heavy metals during the HTT related to their own properties, and their transferring behaviors were different with the increase of HTT time. Compared with the raw sludge, the contents of Cu, Zn, Cr and Pb in the dewatered sludge increased significantly, As increased slowly, while Ni and Cd were first lower than those in raw sludge, and then increased with the prolonging HTT time.

[Nutrient composition changes in coastal waters of Tangshan Bay, Hebei, China under anthropogenic influence].

Based on the principal component analysis (PCA), data from 25 marine monitoring stations in Tangshan Bay from 1995 to 2012 were collected to study the change of nutrient composition in Tangshan Bay under anthropogenic influence. Results showed that the inorganic nitrogen (DIN) presented an obvious increase trend in the near 20 years, while the PO4³â»-P and SiO3²â»-Si presented a decrease trend. The average N:P ratio increased from 3.0 in 1995 to 26.0 in 2012, but the average Si:N ratio decreased, indicating the nutrient structure in seawater had substantially changed in the near 20 years. According to the results of PCA, the change of water quality was identified. The analysis extracted the first two principal components (PC). PC1 was associated with DIN, NO3⁻-N, NH4⁺-N, PO4³â»-P and NO2⁻-N, which explained 71.5% of the variance. PC2 was characterized by Chl a and SiO3²â»-Si, which explained 21.8% of the variance. It indicated that the water quality of Tangshan bay was closely related to DIN and PO4³â»-P. The two principal component scores revealed the interannual change trend of water quality in the Tangshan Bay under anthropogenic influence, which changed from the N limitation before development and at early stage of development (1995-2005) to the P limitation after development (since 2007). The nutrient composition in Tangshan Bay had changed significantly under anthropogenic influence, therefore, special attention is needed on the the change of nutrients in seawater of Tangshan Bay, especially the increase of inorganic nitrogen content.

[Effects of Hemerocallis citrine baroni flavonids on CCl4-induced liver fibrosis of rats].

This study is designed to explore the possible effects of Hemerocallis citrina baroni flavonids (HCBF) on liver fibrosis induced by CCl4 in rats. The liver fibrosis model was induced by CCl4, and HCBF were administered by gastric perfusion at 25 and 50 mg x kg(-1) qd for 50 days, while the contents of alanine transaminase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), superoxide dismutase (SOD), maleic dialdehyde (MDA) and transforming growth factor-ß1 (TGF-ß1) were measured and the contents of PINP were measured in liver tissue, and the expression of TGF-ß1 were observed by immunohistochemisty and Western blot. The pathological changes of liver tissue were examined by HE. The results showed that HCBF (25, 50 mg x kg(-1)) improved the liver function significantly through reducing the level of ALT, AST, GGT and ALP (P < 0.05 or P < 0.01), and increasing the content of SOD (P < 0.01), while reducing the content of MDA (P < 0.05 or P < 0.01), the expression of TGF-ß1 (P < 0.05) and the content of PINP (P < 0.05). The results suggest that HCBF (25, 50 mg x kg(-1)) may inhibit the liver injury induced by CCl4 by decreasing the oxidative stress.

Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis.

UNLABELLED: Cancer-associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer-associated MSCs (LC-MSCs) and hepatocellular carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC-MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC-MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC-MSCs compared with liver normal MSCs (LN-MSCs) from adjacent cancer-free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC-MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)-155 in HCC cells was significantly up-regulated by coculture with LC-MSCs and by S100A4 ectopic overexpression. The invasion-promoting effects of S100A4 were significantly attenuated by a miR-155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR-155 expression in HCC cells. We demonstrate that S100A4 secreted from LC-MSCs promotes the expression of miR-155, which mediates the down-regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. CONCLUSION: S100A4 secreted from LC-MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013).

The proteasome inhibitor CEP-18770 enhances the anti-myeloma activity of bortezomib and melphalan.

The anti-multiple myeloma (MM) efficacy of bortezomib has led to the development of other proteasome inhibitors (PI), including CEP-18770 which has shown anti-MM effects in preclinical studies. However, the efficacy of orally (PO) or intravenously (IV) administered CEP-18770 in multiple MM models and in combination with conventional anti-MM therapies has not been evaluated. Herein, we show that CEP-18770 combined with melphalan or bortezomib induces synergistic inhibition of MM cell viability in vitro. In MM xenograft models, the addition of CEP-18770 IV to melphalan completely prevented the growth of both melphalan-sensitive and melphalan-resistant tumours. The combination of CEP-18770 IV and bortezomib induced complete regression of bortezomib-sensitive tumours and markedly delayed progression of bortezomib-resistant tumours compared to treatment with either agent alone. Single agent CEP-18770 PO also showed marked anti-MM effects in these xenograft models. These studies provide strong preclinical rationale for further development of this novel PI in the treatment of MM as a monotherapy as well as combined with either melphalan or bortezomib.