Electrosprayed Fiber with Controllable Pore Size for Tissue Regeneration

Architecture of 3D scaffold is closely related to cell behaviors such as cell infiltration, cell attachment, cell growing and cell colonization in 3D scaffold. The influence of 3D scaffold on the cell behavior is very important to understand the nature of cells in artificial 3D structure and to design better 3D scaffold. Thus, the thin layer of nano or microsize fibers made of synthetic (polycaprolactone or PCL) and natural (gelatin) polymer are fabricated using novel electrospraying process. I designed the innovative collector plate with void gaps and developed novel process with the collector plate to fabricate large and controllable pore size. Physical (pore diameter, shape factor, and pore size), mechanical (load-extension curve), chemical (gelatin distribution on single fiber, stability test of single fiber under physiological condition) were evaluated. Using human fibroblast and the thin layers of the large and controllable new fibers, the cell cultures study was carried out in serum free media or in serum media. The multilayer of cell culture was developed using layer-by-layer assembly methods. The cell morphology was confirmed by using confocal and light microscope, SEM. The cells were stained with Alexa Fluor 546, DAPI, and CFDA-SE for morphology study and H & E staining for cell histology. The cell glued 3D scaffold with multilayer was confirmed by tailoring random area of the scaffold.Findings and Conclusions: The novel collector plate allowed the new fiber with large pore size and the pore size to be controllable by manipulating the deposit volume and the size of the circular void gap in the collector plate. The fiber diameter is independent of the new collector plate and they are related to the electrospraying parameters such as the distance between the needle tip and the collector plate. The shape of the void gap affects the alignment of the fiber on the edge of the triangular shape but in circular and rectangular shape of the void gap, fibers were randomly oriented. While 30 day cell culture using PCL fibers and serum added media, some cells were infiltrating through large pore and other cells are attaching on the fiber, growing on or between the fibers not only horizontally but also vertically, colonizing each other, and merging three layers of the fibers into one stable 3D scaffold, finally becoming cell-glued thick 3D scaffold even after tailoring the aluminum frame since cell acts as a glue. The shape of single cell on PCL/gelatin single nanofibers in serum free media was regulated by the configuration of single fibers, not the period of cell culture from 3hr to 24 hr.School of Chemical Engineerin

Surgical castration efficiently delays the time of starting a systemic chemotherapy in castration-resistant prostate cancer patients refractory to initial androgen-deprivation therapy

AbstractBackgroundThe aim of this study was to investigate the effects of surgical castration, particularly delaying the time to entrance of systemic chemotherapy, in castration-resistant prostate cancer (CRPC) patients who were refractory to initial combination androgen deprivation therapy.Materials and methodsWe analyzed the clinical data of 14 CRPC patients diagnosed at Seoul National University Bundang Hospital (SNUBH) from November 2008 through May 2015. After exclusion of three patients, we finally analyzed the baseline characteristics of 11 CRPC patients. We also assessed the delaying time of docetaxel administration, which was defined as response duration, after surgical castration.ResultsAfter bilateral orchiectomy, the treatment response rate was 45.4% and the median duration of response was 9 months (range 4–48 mo). Responders had less aggressive biopsy Gleason scores compared to nonresponders. Notably, responders showed the reducing pattern of serum prostate specific antigen levels, while nonresponders demonstrated increasing tendency after surgical castration. Moreover, responders also presented with a reduction pattern of serum testosterone levels, whereas nonresponders showed an increasing pattern of testosterone levels after bilateral orchiectomy.ConclusionsIn summary, despite the limited number of cases for convincing evidence, our results shed light again on the clinical benefits of surgical castration prior to the systemic chemotherapy in some CRPC patients after initial hormone therapy

Importance of remission and residual somatic symptoms in health-related quality of life among outpatients with major depressive disorder: a cross-sectional study

Background: Major depressive disorder (MDD) is strongly associated with an impaired quality of life (QoL), which is itself affected by various factors. Symptom-oriented ratings poorly reflect the impact of disease on the QoL and level of functioning of the mental health of subjects. The purpose of this study was to assess health-related QoL (HRQoL) using preference-based measures in outpatients with MDD with regard to their remission achievement and clinical factors affecting the HRQoL. Methods: This was a cross-sectional observational study. We recruited 811 patients with MDD from 14 psychiatric outpatient clinics in Korea. They were divided into three groups as follows: a new visit group (n = 287), a remitted group (n = 235), and a non-remitted group (n = 289). The 17-item Hamilton Depression Rating Scale was used to assign patients to the remitted or non-remitted group. The general HRQoL was assessed with the EuroQol 5D (EQ-5D), using both the EQ-5D index score and the EuroQol Visual Analog Scale (EQ-VAS). The disease-specific HRQoL was assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Results: The non-remitted group showed a significant impairment of HRQoL in view of the subscales of EQ-5D index scores, EQ-VAS, and Q-LES-Q-SF. The EQ-5D index score in the remitted group was 0.77 ± 0.10, while it was 0.57 ± 0.23 in the non-remitted group and 0.58 ± 0.24 in the new visit group (p < 0.0001). The EQ-VAS scores for the remitted and non-remitted groups were 72.5 ± 16.6 and 50.9 ± 20.3, respectively (p < 0.0001). Likewise, patients with remission had the Q-LES-Q-SF total score of 46.5 ± 8.8, whereas those with non-remission reported 36.7 ± 7.7 (p < 0.0001). The symptom severity measured by the Depression and Somatic Symptoms Scale was significantly correlated with the HRQoL. Furthermore, patients with severe somatic symptoms showed a significantly lower EQ-5D index score (0.54 ± 0.24) than those with mild/moderate somatic symptoms (0.75 ± 0.12; p = 0.002). Conclusion: Non-remitted MDD patients, especially those with more severe somatic symptoms, show a distinct impairment of HRQoL and more clinical symptoms, suggesting the importance of achieving remission in the treatment of MDD

The C-terminal region of Bfl-1 sensitizes non-small cell lung cancer to gemcitabine-induced apoptosis by suppressing NF-κB activity and down-regulating Bfl-1

Gemcitabine is used to treat several cancers including lung cancer. However, tumor cells often escape gemcitabine-induced cell death via various mechanisms, which include modulating bcl-2 family members and NF-κB activation. We previously reported that the C-terminal region of Bfl-1 fused with GFP (BC) is sufficient to induce apoptosis in 293T cells. In the present study, we investigated the anti-tumor effect of combined BC gene therapy and gemcitabine chemotherapy in vitro and in vivo using non-small cell lung cancer cell lines and a xenograft model. Cell lines were resistant to low dose gemcitabine (4-40 ng/ml), which induced NF-κB activation and concomitant up-regulation of Bfl-1 (an NF-κB-regulated anti-apoptotic protein). BC induced the apoptosis of A549 and H157 cells with caspase-3 activation. Furthermore, co-treatment with BC and low dose gemcitabine synergistically and efficiently induced mitochondria-mediated apoptosis in these cells. When administered alone or with low dose gemcitabine, BC suppressed NF-κB activity, inhibited the nuclear translocation of p65/relA, and down-regulated Bfl-1 expression. Furthermore, direct suppression of Bfl-1 by RNA interference sensitized cells to gemcitabine-induced cell death, suggesting that Bfl-1 importantly regulates lung cancer cell sensitivity to gemcitabine. BC and gemcitabine co-treatment also showed a strong anti-tumor effect in a nude mouse/A549 xenograft model. These results suggest that lung cancer cells become resistant to gemcitabine via NF-κB activation and the subsequent overexpression of Bfl-1, and that BC, which has both pro-apoptotic and NF-κB inhibitory effects, could be harnessed as a gene therapy to complement gemcitabine chemotherapy in non-small cell lung cancer

Changes in the Reflux Symptom Index After Multilevel Surgery for Obstructive Sleep Apnea

Objectives This study evaluated whether the symptoms of laryngopharyngeal reflux (LPR) change after multilevel surgery for obstructive sleep apnea (OSA). Methods Patients who underwent multilevel surgery for OSA between April 2009 and September 2014 were enrolled in this study. All patients underwent preoperative polysomnography prior to surgery and were asked to complete the reflux symptom index (RSI) questionnaire before and after surgery. Results Of 73 enrolled patients, 24 (33%) reported an RSI score >13 and were thus classified as having reflux. The mean RSI score before surgery was 11.48±7.95; this number decreased to 4.95±6.19 after surgery (P<0.001). The rate of positive RSI responses was 33% before surgery and 9% after surgery. Each variable that comprised the RSI improved significantly after surgery, except for difficulty with swallowing. Regarding the degree of RSI improvement after surgery, there were no significant differences between subgroups according to sex, age, body mass index, OSA severity, or surgical outcome. Conclusion LPR symptoms are prevalent in OSA patients. Treatment for OSA using multilevel surgery potentially reduces the symptoms of LPR