Crude extract of Rheum palmatum L induced cell death in LS1034 human colon cancer cells acts through the caspase‐dependent and ‐independent pathways

Crude extract of Rheum palmatum L (CERP) has been used to treat different diseases in the Chinese population for decades. In this study, we investigated the effects of CERP on LS1034 human colorectal cancer cells in vitro and also examined possible mechanisms of cell death. Flow cytometric assays were used to measure the percentage of viable cells, cell cycle distribution including the sub‐G1 phase (apoptosis), the activities of caspase‐8, ‐9, and ‐3, reactive oxygen species (ROS) and Ca²⁺ levels, and mitochondrial membrane potential (ΔΨ_m). DNA damage, nuclei condensation, protein expression, and translocation were examined by Comet assay, 4′‐6‐diamidino‐2‐phenylindole (DAPI) staining, Western blotting, and confocal laser system microscope, respectively. CERP induced apoptosis as seen by DNA fragmentation and DAPI staining in a concentration‐ and time‐dependent manner in cancer cells. CERP was associated with an increase in the Bax/Bcl‐2 protein ratio and CERP promoted the activities of caspase‐8, ‐9, and ‐3. Both ROS and Ca²⁺ levels were increased by CERP but the compound decreased levels of ΔΨ_m in LS1034 cells. Laser confocal microscope also confirmed that CERP promoted the expressions of AIF, Endo G, cytochrome c, and GADD153 to induce apoptosis through mitochondrial‐dependent pathway. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 969–980, 2014.     

Anaemia management in patients with chronic kidney disease: Taiwan practice guidelines

The introduction of erythropoiesis‐stimulating agents (ESAs) markedly improved the lives of many anaemic patients with chronic kidney disease (CKD). In Taiwan, the strategy of management of anaemia in patients with CKD was different from many other parts of the world. In 1996, the National Health Insurance Administration of Taiwan applied a more restrictive reimbursement criteria for ESA use in patients with CKD. ESA is to be initiated when non‐dialysis CKD patients have a serum creatinine >6 mg/dL and a hematocrit <28% to maintain a hematocrit level not exceeding 30%. The maximal dose of epoetin‐α or β was 20 000 U per month. The target haemoglobin range and dose limitation for ESAs were the same for dialysis CKD patients. Thus, long before randomized controlled trials showing an increased risk for cardiovascular events at nearly normal haemoglobin concentrations and higher ESA doses in CKD, nephrologists in Taiwan had avoided the use of disproportionately high dosages of ESAs to achieve a haemoglobin level of 10–11 g/dL. Moreover, intravenous iron supplementation was encouraged earlier in Taiwan in 1996, when we reached consensus on the diagnostic criteria for iron deficiency (serum ferritin <300 ng/mL and/or transferrin saturation <30%). The experience of CKD anaemia management in Taiwan demonstrated that a reasonable haemoglobin target can be achieved by using the lowest possible ESA dose and intravenous iron supplementation.     

Clinical Outcomes Following Covered Stent for the Treatment of Coronary Artery Perforation

Background

This study aimed to evaluate short‐ and long‐term outcomes of polytetrafluoroethylene covered stent for patients with coronary artery perforation.

Methods

During April 2004 and February 2016, a total 48 patients underwent implantation using polytetrafluoroethylene‐covered JOSTENT GraftMaster stents (Abbott Vascular, Santa Clara, CA) in the native coronary arteries implantation for coronary artery perforation. Clinical outcomes such as target lesion revascularization (TLR), myocardial infarction (MI), definite or possible stent thrombosis, cardiovascular mortality, and all‐cause mortality were analyzed.

Results

The average age of study patients was 68.02 ± 13.49 years, and the majorities were men (76.6%). The most frequent devices cause of perforation were stents (37.5%). Eighteen patients (37.5%) experienced cardiac tamponade and 20 patients (41.7%) underwent emergent pericardiocentesis. Only 1 patient (2.1%) experienced emergent surgical repair after covered stent. At the 30‐day follow‐up, the rate of all‐cause mortality was 16.7% and cardiovascular mortality was 13.0%. At the 1‐year follow‐up, the rate of MI was 6.1%, the rate of TLR was 21.9%, the rate of definite or possible stent thrombosis was 15.6%, the rate of cardiovascular mortality was 22.0%, and the rate of all‐cause mortality was 26.2%. Between the patients with and without cardiac tamponade, patients with cardiac tamponade had higher cardiovascular mortality in 30‐day and also higher all‐cause mortality in 30‐day and 1‐year follow‐up.

Conclusion

The covered stent could solve emergent condition for patients with coronary artery perforation with high TLR and stent thrombosis rate at long‐term follow‐up. The patients with cardiac tamponade had worse clinical outcomes in 30‐day and 1‐year follow‐up.

     

Alpinia oxyphylla Miq extract ameliorates cardiac fibrosis associated with D‐galactose induced aging in rats

Cardiac fibrosis is a common pathophysiological process observed during chronic and stress‐induced acceleration of cardiac aging. Fibrosis is a necessary process during wound healing and tissue repair. However, its deposition in organs would proceed to scarring and organ damage. Here Alpinate Oxyphyllae Fructus (AOF), a Chinese medicine extract was used to protect aging heart from collagen accumulation. About 8 weeks old, male SD rats were randomly divided into (i) Control, (ii) D‐galactose induced aging (IA), (iii) IA + AOF 50 (AOF low, AL), (iv) IA + AOF 100 (AOF medium, AM), (v) IA + AOF 150 (AOF high, AH) mg/kg/day, AOF was administered orally. After 8 weeks rats were sacrificed and hearts were collected. Results showed collagen deposition and up‐regulation of matrix metalloproteinases‐MMP‐2 and ‐9 in D‐galactose‐induced aging rats. Furthermore, western blotting and immunostaining were also confirmed the upregulation of TGF‐β1 mediated fibrosis in aging induced rats. However, collagen deposition and fibrosis were significantly decreased by AOF treatments (AM and AH). AOF treatments salvaged the cardiac fibrosis. Hence, AOF might be a potential therapeutic agent in the prevention of cardiac fibrosis associated with aging. The protective effects of AOF might have promising results in anti‐aging treatments.     

Coronarin D induces human oral cancer cell apoptosis though upregulate JNK1/2 signaling pathway

The incidence of oral cancer is increasing all over the world, with rates particularly high in Southeast Asian countries, such as Taiwan. Coronarin D (CD) has been confirmed to have anti‐inflammatory, anti‐bacterial effects, and anti‐apoptotic effects in human hepatocellular carcinoma and nasopharyngeal carcinoma. The purpose of this study is to explore whether CD has a suppression effect on oral cancer cells and the mechanisms involved. The results of our study revealed the significantly decreased cancer cell viability and increased activation of apoptosis via increased loss of mitochondrial membrane potential, increased death receptors, leading to the activation of caspase‐8, ‐9, ‐3. Moreover, the rate of apoptosis of cells treated with CD plus JNK inhibitors was decreased compared to CD‐treated cells. This is the first study to demonstrate that CD induces apoptosis in human oral cancer cells and can be expected to be a promising anticancer agent for oral cancer treatment.