Persistent stress urinary incontinence during pregnancy and one year after delivery; its prevalence,risk factors and impact on quality of life in Taiwanese women: An observational cohort study

Objective

The study was to investigate the prevalence and risk factors of stress urinary incontinence (SUI) and its impact on the quality of life during pregnancy and 12 months after delivery.

Colon cancer stem cells resist antiangiogenesis therapy-induced apoptosis

Antiangiogenesis is an efficient therapy for eliminating colon cancers, but because of recurrence it remains only palliative. We hypothesized that certain populations of tumor cells resist antiangiogenesis-induced apoptosis and explored the underlying mechanism. We demonstrated that the CD133⁺ population of cells in colon cancer is resistant to anti-angiogenesis therapy. Additionally, we identified an anti-apoptotic signaling pathway responsible for this resistance involving PP2A, p38MAPK, MAPKAPK2, and Hsp27. Thus, this pathway may offer a new avenue to develop target therapy for colorectal cancer.     

Technical quality of root canal treatment in Taiwan

AIM: To evaluate the current technical quality of root canal treatment (RCT) in Taiwan. METHODOLOGY: A total of 1085 RCT cases, randomly selected from a large sample and representative of the Taiwanese population from April to September 2000, were evaluated by eight endodontic specialists. The qualitative evaluation of RCT cases was based on two variables: length of the root filling and density of the obturation. A root canal with both adequate filling length (the apical termination of the root filling within 2 mm of the radiographic apex) and complete obturation (no lateral or apical canal lumen visible in the apical one-third of the root canal) was defined as having good-quality endodontic work (GQEW). A tooth was defined as having a GQEW when all its canals were categorized as GQEW. RESULTS: From a total of 1867 root canals, overfilling occurred in 235 (12.6%), adequate filling length in 1152 (61.7%), underfilling in 466 (25.0%) and no filling in 12 (0.6%). Of the 1867 root canals, 710 (38.0%) demonstrated complete obturation and 1157 (62%) demonstrated incomplete obturation. GQEW was found in 650 (34.8%) root canals and 329 (30.3%) teeth. The percentage of teeth with GQEW in hospital cases (38.1%) was significantly greater (P < 0.001) than that in private clinic cases (24.3%). In addition, the frequency of teeth with GQEW in the anterior teeth (40.4%) or in the premolars (33%) was significantly greater (P < 0.001) than that in the molars (18.4%). CONCLUSIONS: Approximately 70% of the teeth receiving RCT in Taiwan were either of inadequate filling length or sealing density.     

Mesenchymal stem cell-conditioned medium facilitates angiogenesis and fracture healing in diabetic rats

The most critical factor for fracture union is the blood supply to the fracture site, which is usually impaired in patients with diabetes. Recently, mesenchymal stem cells‐derived conditioned medium (MSC‐CM) has shown significantly higher levels of angiogenic factors, such as VEGF and IL‐6. We demonstrate in this report that MSC‐CM delivered in gelatin sponges stimulates angiogenesis and promotes fracture healing in a diabetic rat model. Subcutaneous implantation of gelatin sponges soaked in MSC‐CM demonstrated better tissue ingrowth and higher capillary densities at 2 and 3 weeks than gelatin sponges in minimal essential medium (MEM) or 293 cell‐derived conditioned medium (293‐CM). Implantation of fibular defects with gelatin sponges soaked in MSC‐CM enhanced bone ingrowth and fracture healing rates compared to 293‐CM and MEM groups at 8 weeks. Micro‐computed tomography analysis further indicated a higher new bone volume in the MSC‐CM group compared to the other diabetic groups. Histological analysis with CD31 immunostaining also revealed that MSC‐CM increased endothelial cell counts compared to the other groups. Together, these results indicated that gelatin sponges used to deliver MSC‐CM promote angiogenesis and fracture healing in a diabetic model and may be an alternative strategy for treating fracture non‐union in patients with diabetes. Copyright © 2011 John Wiley & Sons, Ltd.     

Pml and TAp73 interacting at nuclear body mediate imatinib‐induced p53‐independent apoptosis of chronic myeloid leukemia cells

Bcr‐abl signals for leukemogenesis of chronic myeloid leukemia (CML) and activates ras. Since the function of promyelocytic leukemia protein (pml) is provoked by ras to promote apoptosis and senescence in untransformed cells, the function is probably masked in CML. Imatinib specifically inhibits bcr‐abl and induces apoptosis of CML cells. As reported previously, p53^wild CML was more resistant to imatinib than that lacking p53. Here, we searched for an imatinib‐induced p53 independent proapoptotic mechanism. We found imatinib up‐regulated phosphorylation of p38 mitogen‐activated protein kinase (MAPK), checkpoint kinase 2 (chk2) and transactivation‐competent (TA) p73; expression of pml and bax; formation of PML‐nuclear body (NB); and co‐localization of TAp73/PML‐NB in p53‐nonfunctioning K562 and p53^mutant Meg‐01 CML cells, but not in BCR‐ABL^‐ HL60 cells. In K562 cells, with short interfering RNAs (siRNAs), knockdown of pml led to dephosphorylation of TAp73. Knockdown of either pml or TAp73 abolished the imatinib‐induced apoptosis. Inhibition of p38 MAPK with SB203580 led to dephosphorylation of TAp73, abolishment of TAp73/PML‐NB co‐localization, and the subsequent apoptosis. Conversely, interferon α‐2a (IFNα), which increased phosphrylated TAp73 and TAp73/PML‐NB co‐localization, increased additively apoptosis with imatinib. The imatinib‐induced TAp73/PML‐NB co‐localization was accompanied by co‐immpunoprecipitation of TAp73 with pml. The imatinib‐induced co‐localization was also found in primary CML cells from 3 of 6 patients, including 2 with p53^mutant and one with p53^wild. A novel p53‐independent proapoptotic mechanism using p38 MAPK /pml/TAp73 axis with a step processing at PML‐NB and probably with chk2 and bax being involved is hereby evident in some imatinib‐treated CML cells. © 2009 UICC     

Capsaicin exerts therapeutic effects by targeting tNOX-SIRT1 axis and augmenting ROS-dependent autophagy in melanoma cancer cells

Although considered a sporadic type of skin cancer, malignant melanoma has regularly increased internationally and is a major cause of cancer-associated death worldwide. The treatment options for malignant melanoma are very limited. Accumulating data suggest that the natural compound, capsaicin, exhibits preferential anticancer properties to act as a nutraceutical agent. Here, we explored the underlying molecular events involved in the inhibitory effect of capsaicin on melanoma growth. The cellular thermal shift assay (CETSA), isothermal dose-response fingerprint curves (ITDRF_CETSA), and CETSA-pulse proteolysis were utilized to confirm the direct binding of capsaicin with the tumor-associated NADH oxidase, tNOX (ENOX2) in melanoma cells. We also assessed the cellular impact of capsaicin-targeting of tNOX on A375 cells by flow cytometry and protein analysis. The essential role of tNOX in tumor- and melanoma-growth limiting abilities of capsaicin was evaluated in C57BL/6 mice. Our data show that capsaicin directly engaged with cellular tNOX to inhibit its enzymatic activity and enhance protein degradation capacity. The inhibition of tNOX by capsaicin was accompanied by the attenuation of SIRT1, a NAD⁺-dependent deacetylase. The suppression of tNOX and SIRT1 then enhanced ULK1 acetylation and induced ROS-dependent autophagy in melanoma cells. Capsaicin treatment of mice implanted with melanoma cancer cells suppressed tumor growth by down-regulating tNOX and SIRT1, which was also seen in an in vivo xenograft study with tNOX-depleted melanoma cells. Taken together, our findings suggest that tNOX expression is important for the growth of melanoma cancer cells both in vitro and in vivo, and that inhibition of the tNOX-SIRT1 axis contributes to inducting ROS-dependent autophagy in melanoma cells.