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Cardiac dysfunction is a significant manifestation of sepsis and it is associated with the prognosis of the disease. Astaxanthin (ATX) has been discovered to serve a variety of pharmacological effects, including anti-inflammatory, antioxidant and antiapoptotic properties. The present study aimed to investigate the role and mechanisms of ATX in sepsis-induced myocardial injury. Male C57BL/6 mice were divided into three groups (15 mice per group): Control group, lipopolysaccharide (LPS) group and LPS + ATX group. The cardiac dysfunction model was induced through an intraperitoneal injection of LPS (10 mg/kg) and ATX (40 mg/kg) was administered to the LPS + ATX group by intraperitoneal injection 30 min following the administration of LPS. All animals were sacrificed after 24 h. Inflammatory cytokine levels in the serum were detected using ELISAs, and cardiac B-type natriuretic peptide (BNP) levels were analyzed using western blot analysis and reverse transcription-quantitative PCR. Furthermore, the extent of myocardial injury was evaluated using pathological analysis, and cardiomyocyte apoptosis was analyzed using a TUNEL assay, in addition to determining the expression levels of Bcl-2 and Bax. The expression levels of proteins involved in the mitogen activated protein kinase (MAPK) and PI3K/AKT signaling pathways were also analyzed using western blot analysis. ATX significantly suppressed the LPS-induced increased production of TNF-α and IL-6 and suppressed the protein expression levels of BNP, Bax and Bcl-2 to normal levels. ATX also prevented the histopathological changes to the myocardial tissue and reduced the extent of necrosis. Furthermore, the treatment with ATX suppressed the LPS-activated MAPK and PI3K/AKT signaling. ATX additionally exerted a protective effect on cardiac dysfunction caused by sepsis by inhibiting MAPK and PI3K/AKT signaling.

The purpose of the present study was to explore aging-associated cardiac dysfunction and the possible mechanism by which swimming exercise modulates cardiac dysfunction in aged mice. Aged mice were divided into two groups: i) Aged mice; and ii) aged mice subjected to swimming exercises. Another cohort of 4-month-old male mice served as the control group. Cardiac structure and function in mice were analyzed using hematoxylin and eosin staining, and echocardiography. The levels of oxidative stress were determined by measuring the levels of superoxide dismutase, malondialdehyde and reactive oxygen species (ROS). Levels of the endoplasmic reticulum (ER) stress-related protein PKR-like ER kinase, glucose-regulated protein 78 and C/EBP homologous protein were determined to evaluate the level of ER stress. The aged group exhibited an abnormal cardiac structure and decreased cardiac function, both of which were ameliorated by swimming exercise. The hearts of the aged mice exhibited pronounced oxidative and ER stress, which were ameliorated by exercise, and was accompanied by the reactivation of myocardial cGMP and suppression of cGMP-specific phosphodiesterase type 5 (PDE5). The inhibition of PDE5 attenuated age-induced cardiac dysfunction, blocked ROS production and suppressed ER stress. An ER stress inducer abolished the beneficial effects of the swimming exercise on cardiac function and increased ROS production. The present study suggested that exercise restored cardiac function in mice with age-induced cardiac dysfunction by inhibiting oxidative stress and ER stress, and increasing cGMP-protein kinase G signaling.

The present study aimed to identify differentially expressed genes (DEGs) in colorectal cancer (CRC) and provide novel prognostic biomarkers for CRC. The microarray dataset GSE41258 was used to screen DEGs of CRC. Subsequently, a protein‑protein interaction network of DEGs and Gene Ontology analysis were performed to identify hub genes and associated biological processes. Nebulette (NEBL) and complement C1q like 1 (C1QL1) were validated using reverse transcription‑quantitative polymerase chain reaction in patients with CRC. Survival analysis was performed for the two hub genes. GSE41258 dataset included 182 CRC samples and 54 normal tissues. A total of 759 DEGs, including 279 upregulated and 480 downregulated were screened between both groups. NEBL and C1QL1 were identified as the two hub genes and upregulated genes involved in various biological processes, including 'regulation of biological quality' and 'response to stimulus', respectively. Additionally, the overexpression of NEBL and C1QL1 in experimental validation was consistent with the aforementioned bioinformatics analysis results. Survival analysis suggested that overexpressed NEBL in patients with CRC was associated with a positive prognosis for overall survival. In conclusion, CRC was associated with a large group of DEGs. From the upregulated genes, overexpressed NEBL in patients CRC indicated a positive prognosis for overall survival and may be used as a prognostic biomarker for patients with CRC.

The androgen receptor (AR) has a critical role in prostate cancer development and progression. Several curcumin analogues (A10, B10, C10, E10 and F10) with different linker groups were investigated for their effects in human prostate cancer CWR‑22Rv1 and LNCaP cell lines. The ability of these compounds to inhibit testosterone (TT)‑ or dihydrotestosterone (DHT)‑induced AR activity was determined by an AR‑linked luciferase assay and by TT‑ or DHT‑induced expression of prostate specific antigen. Compounds F10 and E10 had stronger inhibitory effects on the growth of cultured CWR‑22Rv1 and LNCaP cell lines, and they also had enhanced stimulatory effects on apoptosis compared with curcumin and other curcumin analogues (A10, B10, C10) in CWR‑22Rv1 cells. E10 and F10 were more potent inhibitors of AR activity than curcumin, A10 and B10. The higher activities of E10 and F10 may be correlated with a heteroatom linker. The results indicate that one of the potential mechanisms for the anticancer effect of the curcumin analogues was inhibition of AR pathways in human prostate cancer cells.

The mammalian target of rapamycin/eukaryotic translation inititiation factor 4E binding protein 1 (mTOR/4E-BP1) transduction pathway is activated in a range of malignant cancers, but its role in human gastric cardiac adenocarcinoma (GCA) has not been well defined. The present study used western blotting and reverse transcription polymerase chain reaction (RT-PCR) to assess the expression of mTOR, 4E-BP1 and eukaryotic translation initiation factor 4E (eIF4E) at the protein and mRNA levels in 33 cases of GCA and paired adjacent normal gastric mucosal tissues. The expression of mTOR at the protein level in GCA was significantly lower than that in the corresponding normal gastric mucosa (0.296 ± 0.27 vs. 1.348 ± 0.80, P

Sterigmatocystin (ST) is a toxic metabolite mainly produced by the fungi Aspergillus nidulans and Aspergillus versicolor. ST is considered a potent carcinogen, mutagen and teratogen. However, over the past few years, it has been demonstrated that it is less acutely toxic to rodents in vivo. In this study, we evaluated the putative effects of ST on the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-12 at mRNA levels in murine peripheral blood mononuclear cells (mPBMCs) and peritoneal macrophage cells and on the serum TNF-α and IL-6 levels in BALB/c mice. Our results show the downregulation of TNF-α, IL-6 and IL-12 mRNA expression in mPBMCs and peritoneal macrophage cells using semi-quantitative reverse transcription-polymerase chain reaction following ST treatment by intraperitoneal injection. Additionally, serum TNF-α and IL-6 levels were also decreased as shown by enzyme-linked immunosorbent assay (ELISA). These results suggest that ST contamination has negative immunomodulatory effects through the downregulation of cytokine expression and secretion.

The reported effects of nicotine on dendritic cells (DCs) are controversial. To investigate the factors which determine the effects of nicotine on DCs, immature dendritic cells (imDCs) induced from murine bone marrow were treated with different doses of nicotine with or without lipopolysaccharides (LPS). The morphology and expression of the co-stimulatory molecules CD80, CD86, CD40 and CD54 were observed and determined by microscopy and flow cytometry, respectively. The results showed that, firstly, nicotine treatment promoted the development of DC precursors into imDCs with a semi-mature phenotype revealed by a higher expression of CD11c and more branched projections. Secondly, lower doses of nicotine (16.5 ng/ml), but not higher (200 µg/ml), up-regulated the expression of the co-stimulatory molecules CD80, CD40 and CD54 on imDCs. Co-administration of LPS and nicotine revealed differential effects on co-stimulatory molecule expression on imDCs. Thirdly and importantly, treatment with lower doses of nicotine (16.5 ng/ml) did not augment expression of the CD80, CD86, CD40 and CD54 molecules in mature DCs. Fourthly and interestingly, high doses of nicotine (more than 165 µg/ml) revealed pro-apoptotic activity but lower doses of nicotine (16.5-0.165 ng/ml) achieved an anti-apoptotic effect on imDCs. All data presented here indicate that the controversial effects of nicotine on DCs may be due to the LPS of the nicotinic environment and the dose of nicotine used.