OBJECTIVETo investigate the inhibitory activities of norcantharidin (NCTD), a demethylated analogue of cantharidin, on Hep3B cells (a human hepatoma cell line) with deficiency of p53.

METHODSThe survival rate of the Hep3B cells after treating with NCTD was measured by MTT assay. Cell cycle of treated cells was analyzed by flow cytometry, and DNA fragmentation was observed by electrophoresis. The influence of inhibitors for various caspases and anti-death receptors antibodies on the NCTD-induced apoptosis in the cells was determined.

RESULTSNCTD treatment resulted in growth inhibition of Hep3B cells in a dose- and time-dependent manner. Cell cycle analysis of the cells after treatment with NCTD for 48 h shows that NCTD induced G(2)M phase arrest occurs at low concentration ([Symbol: see text] 25 μmol/L) but G(0)G(1) phase arrest at high concentration (50 μmol/L). The addition of both caspase-3 and caspase-10 inhibitors completely inhibited DNA fragmentation. Addition of anti-TRAIL/DR5 antibody significantly inhibited DNA fragmentation.

CONCLUSIONNCTD may inhibit the proliferation of Hep3B cells by arresting cell cycle at G(2)M or G(0)G(1) phase, and induce cells apoptosis via TRAIL/DR5 signal transduction through activation of caspase-3 and caspase-10 by a p53-independent pathway.

Antibodies, Neoplasm ; pharmacology ; Antibodies, Neutralizing ; pharmacology ; Apoptosis ; drug effects ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Caspase 10 ; metabolism ; Caspase 3 ; metabolism ; Caspase Inhibitors ; pharmacology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Fragmentation ; drug effects ; Humans ; Immunohistochemistry ; Liver Neoplasms ; enzymology ; pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Signal Transduction ; drug effects ; TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

Background and Objectives: Hyaluronan preserves the proliferation and differentiation potential of mesenchymal stem cells. Supplementation of low-concentration hyaluronan (SHA) in stem cells culture medium increases its proliferative rate, whereas coated-surface hyaluronan (CHA) maintains cells in a slow-proliferating mode. We have previously demonstrated that in CHA, the metabolic proliferative state of stem cells was influenced by upregulating mitochondrial biogenesis and function. However, the effect of SHA on stem cells’ energetic status remains unknown. In this study, we demonstrate the effect that low-concentration SHA at 0.001 mg/ml (SHA0.001) and high-concentration SHA at 5 mg/ml (SHA5) exert on stem cells’ mitochondrial function compared with CHA and noncoated tissue culture surface (control). Methods: and Results: Fast-proliferating human placenta-derived mesenchymal stem cells (PDMSCs) cultured on SHA0.001 exhibited reduced mitochondrial mass, lower mitochondrial DNA copy number, and lower oxygen consumption rate compared with slow-proliferating PDMSCs cultured on CHA at 5.0 (CHA5) or 30 μg/cm2 (CHA30). The reduced mitochondrial biogenesis observed in SHA0.001 was accompanied by a 2-fold increased ATP content and lactate production, suggesting that hyaluronan-induced fast-proliferating PDMSCs may rely less on mitochondrial function as an energy source and induce a mitochondrial functional switch to glycolysis. Conclusions PDMSCs cultured on both CHA and SHA exhibited a reduction in reactive oxygen species levels. The results from this study clarify our understandings on the effect of hyaluronan on stem cells and provide important insights into the effect of distinct supplementation methods used during cell therapies.

The aim of this study was to determine the correlation of ultrasonographic estimates of testicular volume with true testicular volume and to compare the accuracy and precision of the three most commonly utilized formulas. A total of 15 patients underwent high-resolution ultrasonography (US) analysis for testicular volume before orchiectomy. Testicular volume was calculated using three common formulas: (1) length (L) x width (W) x height (H) x 0.52; (2) the empirical formula of Lambert: L x W x H x 0.71; and (3) L x W2 x 0.52. The actual volume of each removed testis was estimated directly by a water displacement method. Thus, four volume measurements were obtained for each of the 30 testes. The obtained data were analyzed by paired t-test and linear regression analysis. All three US formula measurements significantly underestimated the true testicular volume. The largest mean biases were observed with US formula 1, which underestimated the true volume by 3.3 mL (31%). US formula 2 had a smaller mean difference from the true volume, with an underestimation of only 0.6 mL (6%). Regression analysis showed that formulas 1 and 2 had better R2 values than formula 3. However, all three US formulas displayed a strong linear relationship with the true volume (R2= 0.872-0.977; P < 0.001). Among the commonly used US formulas, the empirical formula of Lambert (L x W x H x 0.71) provided better accuracy than the other two formulas evaluated, and better precision than formula 3. Therefore, the formula of Lambert is the optimal choice in clinical practice.
Aged ; Aged, 80 and over ; Humans ; Male ; Middle Aged ; Organ Size ; Reproducibility of Results ; Testis ; anatomy & histology ; diagnostic imaging ; Ultrasonography ; methods

BACKGROUND/AIMS: With the recent progress in medical treatment, surgery still plays a necessary and important role in treating ulcerative colitis (UC) patients. In this study, we analyzed the surgical results and outcomes of UC in Taiwan in the recent 20 years, via a multi-center study through the collaboration of Taiwan Society of IBD. METHODS: A retrospective analysis of surgery data of UC patients from January 1, 1995, through December 31, 2014, in 6 Taiwan major medical centers was conducted. The patients' demographic data, indications for surgery, and outcome details were recorded and analyzed. RESULTS: The data of 87 UC patients who received surgical treatment were recorded. The median post-operative follow-up duration was 51.1 months and ranged from 0.4 to 300 months. The mean age at UC diagnosis was 45.3±16.0 years and that at operation was 48.5±15.2 years. The 3 leading indications for surgical intervention were uncontrolled bleeding (16.1%), perforation (13.8%), and intractability (12.6%). In total, 27.6% of surgeries were performed in an emergency setting. Total or subtotal colectomy with rectal preservation (41.4%) was the most common operation. There were 6 mortalities, all due to sepsis. Emergency operation and low pre-operative albumin level were significantly associated with poor survival (P=0.013 and 0.034, respectively). CONCLUSIONS: In the past 20 years, there was no significant change in the indications for surgery in UC patients. Emergency surgeries and low pre-operative albumin level were associated with poor survival. Therefore, an optimal timing of elective surgery for people with poorly controlled UC is paramount.
Colectomy ; Colitis, Ulcerative* ; Cooperative Behavior ; Diagnosis ; Emergencies ; Follow-Up Studies ; Hemorrhage ; Humans ; Inflammatory Bowel Diseases* ; Mortality ; Prognosis ; Retrospective Studies* ; Sepsis ; Taiwan* ; Ulcer*

Objectives: Concerns about erythropoietin (EPO) therapy for anemia in patients with end-stage renal disease (ESRD) contributing to potential bone loss and increased fracture risks are growing. This study investigated the impact of EPO administration on the risk of common osteoporotic fractures in ESRD patients. Methods: This population-based retrospective cohort study compared EPO users and non-EPO users among ESRD patients undergoing hemodialysis, diagnosed with ESRD between 2000 and 2014 identified from the National Health Insurance Research Database of Taiwan. The cohorts were matched at a propensity score ratio of 1:1, resulting in equal sample sizes of 2839. Variables related to comorbidities were considered. Results: EPO users exhibited higher cumulative incidences of major osteoporotic fractures, hip fractures, spine fractures, and wrist fractures compared with the non-EPO user (all P < 0.001). In adjusted Cox regression models, higher adjusted subdistribution hazard ratios (aSHRs) were observed for major osteoporotic fractures (2.41, 95% confidence interval [CI] = 2.01–2.89), osteoporotic hip fractures (2.19, 95% CI = 1.69–2.85), spine fractures (2.50, 95% CI = 1.87–3.34), and wrist fractures (2.34, 95% CI = 1.44–3.78) in EPO users than in nonEPO users. The risk of major osteoporotic fractures significantly increased with increasing EPO doses (P for trend < 0.0001), and a similar trend was observed for the risks of osteoporotic spine and wrist fractures. Conclusions Our findings suggest that EPO treatment in patients with ESRD undergoing hemodialysis is associated with an increased risk of osteoporotic fractures.

Objectives: Concerns about erythropoietin (EPO) therapy for anemia in patients with end-stage renal disease (ESRD) contributing to potential bone loss and increased fracture risks are growing. This study investigated the impact of EPO administration on the risk of common osteoporotic fractures in ESRD patients. Methods: This population-based retrospective cohort study compared EPO users and non-EPO users among ESRD patients undergoing hemodialysis, diagnosed with ESRD between 2000 and 2014 identified from the National Health Insurance Research Database of Taiwan. The cohorts were matched at a propensity score ratio of 1:1, resulting in equal sample sizes of 2839. Variables related to comorbidities were considered. Results: EPO users exhibited higher cumulative incidences of major osteoporotic fractures, hip fractures, spine fractures, and wrist fractures compared with the non-EPO user (all P < 0.001). In adjusted Cox regression models, higher adjusted subdistribution hazard ratios (aSHRs) were observed for major osteoporotic fractures (2.41, 95% confidence interval [CI] = 2.01–2.89), osteoporotic hip fractures (2.19, 95% CI = 1.69–2.85), spine fractures (2.50, 95% CI = 1.87–3.34), and wrist fractures (2.34, 95% CI = 1.44–3.78) in EPO users than in nonEPO users. The risk of major osteoporotic fractures significantly increased with increasing EPO doses (P for trend < 0.0001), and a similar trend was observed for the risks of osteoporotic spine and wrist fractures. Conclusions Our findings suggest that EPO treatment in patients with ESRD undergoing hemodialysis is associated with an increased risk of osteoporotic fractures.

Objectives: Concerns about erythropoietin (EPO) therapy for anemia in patients with end-stage renal disease (ESRD) contributing to potential bone loss and increased fracture risks are growing. This study investigated the impact of EPO administration on the risk of common osteoporotic fractures in ESRD patients. Methods: This population-based retrospective cohort study compared EPO users and non-EPO users among ESRD patients undergoing hemodialysis, diagnosed with ESRD between 2000 and 2014 identified from the National Health Insurance Research Database of Taiwan. The cohorts were matched at a propensity score ratio of 1:1, resulting in equal sample sizes of 2839. Variables related to comorbidities were considered. Results: EPO users exhibited higher cumulative incidences of major osteoporotic fractures, hip fractures, spine fractures, and wrist fractures compared with the non-EPO user (all P < 0.001). In adjusted Cox regression models, higher adjusted subdistribution hazard ratios (aSHRs) were observed for major osteoporotic fractures (2.41, 95% confidence interval [CI] = 2.01–2.89), osteoporotic hip fractures (2.19, 95% CI = 1.69–2.85), spine fractures (2.50, 95% CI = 1.87–3.34), and wrist fractures (2.34, 95% CI = 1.44–3.78) in EPO users than in nonEPO users. The risk of major osteoporotic fractures significantly increased with increasing EPO doses (P for trend < 0.0001), and a similar trend was observed for the risks of osteoporotic spine and wrist fractures. Conclusions Our findings suggest that EPO treatment in patients with ESRD undergoing hemodialysis is associated with an increased risk of osteoporotic fractures.

Objectives: Concerns about erythropoietin (EPO) therapy for anemia in patients with end-stage renal disease (ESRD) contributing to potential bone loss and increased fracture risks are growing. This study investigated the impact of EPO administration on the risk of common osteoporotic fractures in ESRD patients. Methods: This population-based retrospective cohort study compared EPO users and non-EPO users among ESRD patients undergoing hemodialysis, diagnosed with ESRD between 2000 and 2014 identified from the National Health Insurance Research Database of Taiwan. The cohorts were matched at a propensity score ratio of 1:1, resulting in equal sample sizes of 2839. Variables related to comorbidities were considered. Results: EPO users exhibited higher cumulative incidences of major osteoporotic fractures, hip fractures, spine fractures, and wrist fractures compared with the non-EPO user (all P < 0.001). In adjusted Cox regression models, higher adjusted subdistribution hazard ratios (aSHRs) were observed for major osteoporotic fractures (2.41, 95% confidence interval [CI] = 2.01–2.89), osteoporotic hip fractures (2.19, 95% CI = 1.69–2.85), spine fractures (2.50, 95% CI = 1.87–3.34), and wrist fractures (2.34, 95% CI = 1.44–3.78) in EPO users than in nonEPO users. The risk of major osteoporotic fractures significantly increased with increasing EPO doses (P for trend < 0.0001), and a similar trend was observed for the risks of osteoporotic spine and wrist fractures. Conclusions Our findings suggest that EPO treatment in patients with ESRD undergoing hemodialysis is associated with an increased risk of osteoporotic fractures.

Objectives: Concerns about erythropoietin (EPO) therapy for anemia in patients with end-stage renal disease (ESRD) contributing to potential bone loss and increased fracture risks are growing. This study investigated the impact of EPO administration on the risk of common osteoporotic fractures in ESRD patients. Methods: This population-based retrospective cohort study compared EPO users and non-EPO users among ESRD patients undergoing hemodialysis, diagnosed with ESRD between 2000 and 2014 identified from the National Health Insurance Research Database of Taiwan. The cohorts were matched at a propensity score ratio of 1:1, resulting in equal sample sizes of 2839. Variables related to comorbidities were considered. Results: EPO users exhibited higher cumulative incidences of major osteoporotic fractures, hip fractures, spine fractures, and wrist fractures compared with the non-EPO user (all P < 0.001). In adjusted Cox regression models, higher adjusted subdistribution hazard ratios (aSHRs) were observed for major osteoporotic fractures (2.41, 95% confidence interval [CI] = 2.01–2.89), osteoporotic hip fractures (2.19, 95% CI = 1.69–2.85), spine fractures (2.50, 95% CI = 1.87–3.34), and wrist fractures (2.34, 95% CI = 1.44–3.78) in EPO users than in nonEPO users. The risk of major osteoporotic fractures significantly increased with increasing EPO doses (P for trend < 0.0001), and a similar trend was observed for the risks of osteoporotic spine and wrist fractures. Conclusions Our findings suggest that EPO treatment in patients with ESRD undergoing hemodialysis is associated with an increased risk of osteoporotic fractures.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.