Association of TNF-α, IGF-1, and IGFBP-1 levels with the severity of osteopenia in mice with nonalcoholic fatty liver disease.

BACKGROUNDS: Nonalcoholic fatty liver disease (NAFLD) exhibits a close association with osteoporosis. This work aims to assess the potential effects of NAFLD on the progression of osteopenia in animal models. METHODS: Forty-eight C57BL/6 female mice were randomly divided to wild-type (WT) group and high-fat diet (HFD) group. The corresponding detections were performed after sacrifice at 16, 24 and 32 weeks, respectively. RESULTS: At 16 weeks, an remarkable increase in body weight and lipid aggregation in the hepatocytes of HFD group was observed compared to the WT group, while the bone structure parameters showed no significant difference. At 24 weeks, the levels of TNF-α and IL-6 in NAFLD mice were significantly increased, while the level of osteoprotegerin mRNA in bone tissue was decreased, and the level of receptor activator of nuclear factor Kappa-B ligand mRNA was increased. Meanwhile, the function of osteoclasts was increased, and the bone microstructure parameters showed significant changes. At 32 weeks, in the HFD mice, the mRNA levels of insulin-like growth factor-1 (IGF-1), runt-related transcription factor 2, and osterix mRNA were reduced, while the insulin-like growth factor binding protein-1 (IGFBP-1) level was increased. Simultaneously, the osteoblast function was decreased, and the differences of bone structure parameters were more significant, showing obvious osteoporosis. CONCLUSIONS: The bone loss in HFD mice is pronounced as NAFLD progresses, and the changes of the TNF-α, IL-6, IGF-1, and IGFBP-1 levels may play critical roles at the different stages of NAFLD in HFD.

Protective effect of SIRT3 on acute lung injury by increasing manganese superoxide dismutase-mediated antioxidation.

Prolonged exposure to hyperoxia results in acute lung injury (ALI). Pulmonary damage caused by oxygen toxicity occurs due to the generation of reactive oxygen species and subsequent formation of more potent oxidants. The present study demonstrated that sirtuin 3 (SIRT3) may attenuate hyperoxia­induced ALI due to its potential antioxidative effect. In the present study, a hyperoxia­induced acute lung injury mouse model, reverse transcription­quantitative polymerase chain reaction, western blotting, retroviral mediated gene over­expression and knockdown assays revealed that the expression of SIRT3 in the lung tissue of mice with hyperoxia­induced ALI was decreased and overexpression of SIRT3 may significantly reduce hyperoxia­induced ALI, as reflected by decreases in protein concentration, infiltrated neutrophils in bronchoalveolar lavage (BAL) fluid and wet/dry ratio of lung tissues. Furthermore, overexpression of SIRT3 increased the protein levels and enzymatic activity of manganese superoxide dismutase (MnSOD), and inhibited oxidative stress in the lungs of ALI mice. Additionally, the current study demonstrated that SIRT3 promoted the expression of MnSOD, and this regulation was crucial for the protective effect of SIRT3 on hyperoxia­induced ALI. In summary, the results of the current study indicated that SIRT3 overexpression may effectively ameliorate hyperoxia­induced ALI in mice, which indicates a potential application for SIRT3­based gene therapy to treat clinical adult respiratory distress syndrome.

[Influence of artificial pneumoperitoneal media on colon carcinoma cell proliferation in vitro].

OBJECTIVE: To evaluate the influence of different pneumoperitoneal media on colon carcinoma LS-174T cell proliferation in vitro. METHODS: The artificial pneumoperitoneum was established. The proliferation of LS-174T cells was detected by MTT assay and soft agar clone formation assay. Expression of HIF-1alpha and VEGF was examined by immunohistochemistry. Apoptosis of LS-174T cells was analyzed by AO/EB double fluorescein stain and flow cytometry. RESULTS: The growth speed and proliferating capacity of LS-174T cells in CO(2) pneumoperitoneum group[A:0.37 +/- 0.02,formation (32.8 +/- 3.6)%] were significantly higher than those in control group [A:0.33 +/- 0.01,formation (28.4 +/- 2.3)%] and He group [A:0.30 +/- 0.01,formation (23.5 +/- 2.7)%], meanwhile the He group was the lowest (P<0.01). Positive expression of HIF-1alpha and VEGF in CO(2) and He artificial pneumoperitoneum up-regulated significantly as compared to control group(P<0.01), meanwhile the above expression was higher in CO(2) group (P<0.01). The G(0 )/G(1) ratio in CO(2) group was the lowest as compared to control group and He group (P<0.01), and G(0 )/G(1) ratio in He group was higher than that of control group(P<0.01). Aapoptosis rate in He group was the highest as compared with the other two groups(P<0.01). CONCLUSION: CO(2) pneumoperitoneum has stronger effect on the proliferation of colon carcinoma cell LS-174T as compared to He pneumoperitoneum in vitro.