Casticin Induces DNA Damage and Impairs DNA Repair in Human Bladder Cancer TSGH-8301 Cells.

BACKGROUND/AIM: Casticin shows anti-cancer effects in many types of cancer. However, there is no information regarding its role in DNA damage in human bladder cancer. The aim of this study was to investigate the effects of casticin on TSGH-8301 cells in vitro. MATERIALS AND METHODS: Viability of cells was assayed by flow cytometry. DNA damage was assayed by DAPI staining, comet assay, and gel electrophoresis. Protein levels were examined by western blotting and confocal laser microscopy. RESULTS: Casticin decreased viability of cells and induced DNA damage. Furthermore, casticin decreased expression of p-ATM, p-ATR, MDC1 and MGMT levels after 48 h of treatment, however, it increased p-ATR and MGMT levels after 12 h. In contrast, casticin increased the levels of p-p53, p-H2A.X, and PARP after 48 h of treatment. As shown by confocal microscopy, casticin affected the translocation of DNA-PKcs and p-p53 to the nucleus of TSGH-8301 cells. CONCLUSION: Casticin decreased viability of human bladder cancer cells through DNA damage.

Serum ferritin is associated with arterial stiffness in hemodialysis patients: results of a 3-year follow-up study.

BACKGROUND: Iron may contribute to vascular injury through reactive oxygen species. Hemodialysis patients frequently receive iron supply for correction of anemia and are at a high risk of cardiovascular disease. We tested the relationship between iron status and change in arterial stiffness in hemodialysis patients. PATIENTS AND METHODS: We measured iron status in 53 hemodialysis patients and studied the association with clinical, biochemical, and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) over 3 years. The blood pressure was controlled to below 140/90 mmHg by anti-hypertensive drugs. RESULTS: Median and interquartile range of baseline baPWV, baPWV at 3 years, and ΔbaPWV (difference between 3-year baPWV and baseline baPWV) were following: 17.6 (14.8-18.9), 16.9 (15.3-19.9), and 0.2 (-1.2 to 2.7) m/s. At baseline, baPWV was positively correlated with age, serum ferritin, and systolic blood pressure in univariate analysis. However, in multivariate analysis, only age and serum ferritin remained the significant determinants of baseline baPWV. After 3 years, ΔbaPWV was negatively correlated with age and positively with 3-year averaged serum ferritin in univariate analysis. Then, in multivariate analysis, only 3-year averaged serum ferritin was the important determinant of ΔbaPWV. ΔbaPWV was significantly increased in patients with 3-year averaged serum ferritin >500 ng/mL compared to patients with 3-year averaged serum ferritin ≤500 ng/mL. CONCLUSIONS: In hemodialysis patients, serum ferritin associates with the progressive arterial stiffness, especially when serum ferritin >500 ng/mL.

Anti-platelet factor 4/heparin antibody is associated with progression of peripheral arterial disease in hemodialysis patients.

BACKGROUND: Heparin therapy may induce anti-platelet factor 4/heparin antibody (PF4-H Ab). Hemodialysis patients receive scheduled heparin and are at a risk of developing PF4-H Ab. Hemodialysis patients are also at a high risk of peripheral arterial disease (PAD). This study examines whether chronic PF4-H Ab exposure contributes to the progression of PAD measured by ankle brachial index (ABI) in hemodialysis patients. MATERIALS AND METHODS: A total of 71 hemodialysis patients were enrolled, and the association between clinical, biochemical parameters and ABI after 3 years was studied. PF4-H Ab was evaluated by ELISA, and patients with titer ≥ 0.4 were taken as having PF4-H Ab. RESULTS: Mean ABI was 1.04 ± 0.18 at baseline and 1.01 ± 0.17 after 3 years. Mean ΔABI (change in ABI after 3 years) was -0.04 ± 0.13. PF4-H Ab was positive in 26 patients. PF4-H Ab was not related to hemodialysis duration, DM history, smoking and age. Platelet count showed no correlation with PF4-H Ab. However, there was significance in ΔABI between PF4-H Ab-positive and PF4-H Ab-negative patients (p = 0.002). ΔABI was negatively correlated with PF4-H Ab and 3-year averaged serum Ca × P only (ß = -0.378, p = 0.001; ß = -0.263, p = 0.018, respectively). However, in PF4-H Ab-positive patients, the extent of ΔABI did not correlate with PF4-H Ab titers (r = -0.021, p = 0.921). CONCLUSIONS: PF4-H Ab positivity, along with high levels of serum Ca × P, played a potential role in the progression of PAD over time.

Serum ferritin is associated with progression of peripheral arterial disease in hemodialysis patients.

BACKGROUND: Dialysis patients received intravenous iron to treat anemia and had high prevalence of peripheral artery disease (PAD). We hypothesized that high iron status might associate with the progression of PAD among hemodialysis patients. Therefore, we evaluated the relationship between iron status and progression of PAD. METHODS: We measured iron status in 74 hemodialysis patients and studied the association with clinical, biochemical, and vascular parameters including progression of PAD measured by ankle-brachial index (ABI) over 3 years. RESULTS: Mean baseline ABI was 1.03 ± 0.18. Mean ABI at 3 years was 0.95 ± 0.20. Mean ∆ABI (change in ABI after 3 years) was -0.08 ± 0.14. Serum ferritin was negatively correlated with baseline ABI (r = -0.232, p = 0.046). After 3 years, ∆ABI was negatively associated with 3-year averaged serum ferritin, phosphorus, and calcium-phosphate product (Ca × P) (r = -0.253, p = 0.029; r = -0.278, p = 0.016; r = -0.288, p = 0.013; respectively). After an adjusted model, 3-year averaged serum ferritin and Ca × P remained the significant determinants of ∆ABI (ß = -0.234, p = 0.038; ß = -0.271, p = 0.017; respectively). ∆ABI was significantly different between 3-year averaged serum ferritin level ≥600 and <600 ng/mL (p = 0.032). CONCLUSIONS: In hemodialysis patients, high serum ferritin associates with progression of PAD, especially among those with high Ca x P level.

Effects of Extract from Solid-State Fermented Cordyceps sinensis on Type 2 Diabetes Mellitus.

Diabetes mellitus is the most common chronic disease in the world, and a wide range of drugs, including Chinese herbs, have been evaluated for the treatment of associated metabolic disorders. This study investigated the potential hypoglycemic and renoprotective effects of an extract from the solid-state fermented mycelium of Cordyceps sinensis (CS). We employed the KK/HIJ diabetic mouse model, in which the mice were provided with a high-fat diet for 8 weeks to induce hyperglycemia, followed by the administration of CS or rosiglitazone for 4 consecutive weeks. Several parameters were evaluated, including changes in body weight, plasma lipid profiles, oral glucose tolerance tests, insulin tolerance tests, and plasma insulin concentrations. Our results show that the CS extract significantly elevated HDL/LDL ratios at 4 weeks and decreased body weight gain at 8 weeks. Interestingly, CS treatment did not lead to obvious improvements in hyperglycemia or resistance to insulin, while in vitro MTT assays indicated that CS protects pancreatic beta cells against the toxic effects of STZ. CS also enhanced renal NKA activity and reduced the accumulation of mesangial matrix and collagen deposition. In conclusion, CS extract can potentially preserve ß-cell function and offer renoprotection, which may afford a promising therapy for DM.

Macrophage mediated anti-proliferation effects of Anthodia camphorata non-polysaccharide based extracts on human hepatoma cells.

It has been reported that medicinal mushrooms might induce different types of immune responses. Anthodia camphorata (A. camphorata) has attracted much attention for its therapeutic effects in treating hepatoma. We tested this anti-tumor effects using immunomodulation of macrophages and extracts of A. camphorata. We evaluated the anti-proliferation effects of various extracts of A. camphorata from fruiting bodies (AC-FB), mycelium of solid-state cultures (AC-SS), liquid-state cultures (AC-LS) and polyaccharide extracts from liquid-state cultures (AC-PS), and extracts of A. camphorata stimulated RAW 264.7 macrophage cell-conditioned mediums (MC-CMs). We measured cell proliferation and, did migration assays by cell cycle analysis and by observing apoptosis-related proteins (AKT, PARP-1, and NF-κB) and the mRNA expression of cytokines (TNF-α and IL-1ß) of macrophages in human hepatoma cell lines. Our results revealed that two of the extracts (AC-FB and AC-SS) had better anti-proliferation effects, implying an immunomodulatory role the macrophages might play. This outcome is consistent with findings that AC-FB and AC-SS increase mRNA expression of TNF-α and the corresponding expression of apoptosis-related proteins on activation of MC-CMs, while A. camphorata polysaccharides induce macrophage-derived anti-tumor activities in human hepatoma cells via IL-1ß and Akt activation. These results indicate that anti-tumor effects exerted by modulation of macrophage activation of A. camphorate may be influenced by the other constituents which (contained little or no polysaccharide) of A. camphorata.