Publications by authors named "Hsiung-Fei Chien"

54 Publications

Correction: A COVID-19 Pandemic Artificial Intelligence-Based System With Deep Learning Forecasting and Automatic Statistical Data Acquisition: Development and Implementation Study.

J Med Internet Res 2021 Jul 9;23(7):e31085. Epub 2021 Jul 9.

Professional Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

[This corrects the article DOI: 10.2196/27806.].
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http://dx.doi.org/10.2196/31085DOI Listing
July 2021

Cabozantinib promotes erythroid differentiation in K562 erythroleukemia cells through global changes in gene expression and JNK activation.

Cancer Gene Ther 2021 Jun 11. Epub 2021 Jun 11.

Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.

Cabozantinib is a potent tyrosine kinase inhibitor with multiple targets including MET, VEGFR2, RET, KIT, and FLT3. Cabozantinib is widely used for the treatment of medullary thyroid cancer and renal cell carcinoma. We recently suggested cabozantinib as a potential therapeutic alternative for acute myeloid leukemia (AML) patients with FLT3-internal tandem duplication (FLT3-ITD). Here, we report that cabozantinib can promote differentiation in erythroid leukemia cells. We found that K562 erythroid leukemia cells treated with 1 μM cabozantinib for 72 h underwent erythroid lineage differentiation. Transcriptomic analysis revealed that various pathways associated with heme biosynthesis, hemoglobin production, and GATA1 targets were upregulated, whereas cell survival pathways were downregulated. Further examination revealed that cabozantinib-induced erythroid differentiation is at least in part regulated by JNK activation and phosphorylation. Levels of phosphorylated BCR-ABL, AKT, STAT5, ERK, and p38 also decreased following cabozantinib treatment. Therefore, we indicate that cabozantinib has dual functions. First, it induces K562 cell differentiation toward the erythroid lineage by upregulating heme biosynthesis, globin synthesis, and erythroid-associated reactions. Second, cabozantinib inhibits K562 cell proliferation by inhibiting the phosphorylation of BCR-ABL and the downstream MAPK, PI3K-AKT, and JAK-STAT signaling pathways.
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http://dx.doi.org/10.1038/s41417-021-00358-wDOI Listing
June 2021

A COVID-19 Pandemic Artificial Intelligence-Based System With Deep Learning Forecasting and Automatic Statistical Data Acquisition: Development and Implementation Study.

J Med Internet Res 2021 05 20;23(5):e27806. Epub 2021 May 20.

Professional Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Background: More than 79.2 million confirmed COVID-19 cases and 1.7 million deaths were caused by SARS-CoV-2; the disease was named COVID-19 by the World Health Organization. Control of the COVID-19 epidemic has become a crucial issue around the globe, but there are limited studies that investigate the global trend of the COVID-19 pandemic together with each country's policy measures.

Objective: We aimed to develop an online artificial intelligence (AI) system to analyze the dynamic trend of the COVID-19 pandemic, facilitate forecasting and predictive modeling, and produce a heat map visualization of policy measures in 171 countries.

Methods: The COVID-19 Pandemic AI System (CPAIS) integrated two data sets: the data set from the Oxford COVID-19 Government Response Tracker from the Blavatnik School of Government, which is maintained by the University of Oxford, and the data set from the COVID-19 Data Repository, which was established by the Johns Hopkins University Center for Systems Science and Engineering. This study utilized four statistical and deep learning techniques for forecasting: autoregressive integrated moving average (ARIMA), feedforward neural network (FNN), multilayer perceptron (MLP) neural network, and long short-term memory (LSTM). With regard to 1-year records (ie, whole time series data), records from the last 14 days served as the validation set to evaluate the performance of the forecast, whereas earlier records served as the training set.

Results: A total of 171 countries that featured in both databases were included in the online system. The CPAIS was developed to explore variations, trends, and forecasts related to the COVID-19 pandemic across several counties. For instance, the number of confirmed monthly cases in the United States reached a local peak in July 2020 and another peak of 6,368,591 in December 2020. A dynamic heat map with policy measures depicts changes in COVID-19 measures for each country. A total of 19 measures were embedded within the three sections presented on the website, and only 4 of the 19 measures were continuous measures related to financial support or investment. Deep learning models were used to enable COVID-19 forecasting; the performances of ARIMA, FNN, and the MLP neural network were not stable because their forecast accuracy was only better than LSTM for a few countries. LSTM demonstrated the best forecast accuracy for Canada, as the root mean square error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE) were 2272.551, 1501.248, and 0.2723075, respectively. ARIMA (RMSE=317.53169; MAPE=0.4641688) and FNN (RMSE=181.29894; MAPE=0.2708482) demonstrated better performance for South Korea.

Conclusions: The CPAIS collects and summarizes information about the COVID-19 pandemic and offers data visualization and deep learning-based prediction. It might be a useful reference for predicting a serious outbreak or epidemic. Moreover, the system undergoes daily updates and includes the latest information on vaccination, which may change the dynamics of the pandemic.
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http://dx.doi.org/10.2196/27806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139395PMC
May 2021

Endoscopy-Assisted Total Mastectomy with and without Immediate Reconstruction: An Extended Follow-Up, Multicenter Study.

Plast Reconstr Surg 2021 02;147(2):267-278

From the Division of Plastic Surgery, Department of Surgery, and the Medical Device R & D Core Laboratory, National Cheng Kung University Hospital; the Division of Plastic Surgery, Department of Surgery, College of Medicine, National Cheng Kung University; the Division of Plastic Surgery, Department of Surgery, School of Medicine, College of Medicine, and Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University; the Division of Breast Surgery, Department of Surgery, Taipei Medical University Hospital; the Divisions of Plastic and Reconstructive Surgery and General Surgery, Department of Surgery, the Endoscopic and Oncoplastic Breast Surgery Center, the Comprehensive Breast Cancer Center, and the Minimal Invasive Surgery Research Center, Changhua Christian Hospital; Kaohsiung Medical University; the School of Medicine, National Yang Ming University; the School of Medicine, Chung Shan Medical University; and Chang Gung University College of Medicine.

Background: Endoscopy-assisted total mastectomy has been used for surgical intervention of breast cancer patients; however, large cohort studies with long-term follow-up data are lacking.

Methods: Breast cancer patients who underwent endoscopy-assisted total mastectomy from May of 2009 to March of 2018 were collected prospectively from multiple centers. Clinical outcome, impact of different phases, oncologic results, and patient-reported aesthetic outcomes of endoscopy-assisted total mastectomy were reported.

Results: A total of 436 endoscopy-assisted total mastectomy procedures were performed; 355 (81.4 percent) were nipple-sparing mastectomy, and 81 (18.6 percent) were skin-sparing mastectomy. Three hundred fourteen (75.4 percent) of the procedures were associated with immediate breast reconstruction; 255 were prosthesis based and 59 were associated with autologous flaps. The positive surgical margin rate for endoscopy-assisted total mastectomy was 2.1 percent. In morbidity evaluation, there were 19 cases (5.4 percent) with partial nipple necrosis, two cases (0.6 percent) with total nipple necrosis, and three cases (0.7 percent) with implant loss. Compared with the early phase, surgeons operating on patients in the middle or late phase had significantly decreased operation time and blood loss. With regard to patient-reported cosmetic outcomes, approximately 94.4 percent were satisfied with the aesthetic results. Patients who underwent breast reconstruction with preservation of the nipple had higher satisfaction rates. Over a median follow-up of 54.1 ± 22.4 months, there were 14 cases of locoregional recurrence (3.2 percent), three distant metastases (0.7 percent), and one mortality (0.2 percent).

Conclusion: This multicenter study showed that endoscopy-assisted total mastectomy is a reliable surgical intervention for early breast cancer, with high patient satisfaction.

Clinical Question/level Of Evidence: Therapeutic, IV.
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http://dx.doi.org/10.1097/PRS.0000000000007587DOI Listing
February 2021

Lower proximal cup and outer root sheath cells regenerate hair bulbs during anagen hair follicle repair after chemotherapeutic injury.

Exp Dermatol 2021 Apr 22;30(4):503-511. Epub 2020 Sep 22.

Department of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.

The cell dynamics and cell origin for anagen hair follicle (HF) repair following chemotherapeutic injury are unclear. We first mapped the HF response to cyclophosphamide (CYP) at natural anagen VI in mice. We found that 30-60 mg/kg of CYP leads to dose-dependent HF dystrophy that was spontaneously repaired with anagen resumption, while 120 mg/kg of CYP prematurely induced catagen/telogen entry. To explore how anagen HF repair is achieved in the dystrophic anagen pathway, we analysed the cell dynamics at 30 mg/kg of CYP. Hair bulbs first shrunk due to matrix cell apoptosis associated with DNA double-strand breaks. DNA damage was repaired, and ordered hair bulb structures were restored within 96 hours. Bulge stem cells did not undergo apoptosis nor proliferation. K5 basal lower proximal cup cells and outer root sheath cells quickly replenished the cells in the germinative zone and regenerated the concentric layered structures of the lower HF segment. Therefore, anagen HFs are able to summon extra-bulge progenitor cells in close proximity to the damaged matrix for quick repair after CYP injury.
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http://dx.doi.org/10.1111/exd.14175DOI Listing
April 2021

A Novel Treatment Modality for Malignant Peripheral Nerve Sheath Tumor Using a Dual-Effect Liposome to Combine Photodynamic Therapy and Chemotherapy.

Pharmaceutics 2020 Apr 2;12(4). Epub 2020 Apr 2.

Department of Neurology, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei 10012, Taiwan.

Neurofibromatosis type 1 (NF1) is an inherited neurological disorder. Approximately 5-13% of NF1 patients may develop a malignant peripheral nerve sheath tumor (MPNST), which is a neurofibrosarcoma transformed from the plexiform neurofibroma or schwannoma. Given the large size and easy metastasis of MPNST, it remains difficult to be cured by either surgical or conventional chemotherapy. In this study, we investigated the possibility of combining photodynamic therapy (PDT) and chemotherapy to treat MPNST by using a dual-effect liposome (named as PL-cDDP-Ce6), in which a chemotherapeutic agent, cisplatin (cDDP), and photosensitizer, chlorine e6 (Ce6) were encapsulated in the same carrier. The cytotoxic effect of PL-cDDP-Ce6 against MPNST cells was significantly higher than cells treated with liposomal cDDP or Ce6 alone or in combination after light irradiation. Treatment with the dual-effect liposomes in mice bearing xenograft MPNST tumor reveals a significant increase in survival rate compared to those treated with liposomal cDDP and Ce6 in combination. Moreover, there is no weight loss or derangements of serum biochemistry. In conclusion, this study demonstrates the clinical potential and advantage of using this liposomal drug for the treatment of MPNST.
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http://dx.doi.org/10.3390/pharmaceutics12040317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238030PMC
April 2020

Blockchain-Enabled iWellChain Framework Integration With the National Medical Referral System: Development and Usability Study.

J Med Internet Res 2019 12 4;21(12):e13563. Epub 2019 Dec 4.

Taipei Medical University Hospital, Taipei, Taiwan.

Background: Medical referral is the transfer of a patient's care from one physician to another upon request. This process involves multiple steps that require provider-to-provider and provider-to-patient communication. In Taiwan, the National Health Insurance Administration (NHIA) has implemented a national medical referral (NMR) system, which encourages physicians to refer their patients to different health care facilities to reduce unnecessary hospital visits and the financial stress on the national health insurance. However, the NHIA's NMR system is a government-based electronic medical referral service, and its referral data access and exchange are limited to authorized clinical professionals using their national health smart cards over the NHIA virtual private network. Therefore, this system lacks scalability and flexibility and cannot establish trusting relationships among patients, family doctors, and specialists.

Objective: To eliminate the existing restrictions of the NHIA's NMR system, this study developed a scalable, flexible, and blockchain-enabled framework that leverages the NHIA's NMR referral data to build an alliance-based medical referral service connecting health care facilities.

Methods: We developed a blockchain-enabled framework that can integrate patient referral data from the NHIA's NMR system with electronic medical record (EMR) and electronic health record (EHR) data of hospitals and community-based clinics to establish an alliance-based medical referral service serving patients, clinics, and hospitals and improve the trust in relationships and transaction security. We also developed a blockchain-enabled personal health record decentralized app (DApp) based on our blockchain-enabled framework for patients to acquire their EMR and EHR data; DApp access logs were collected to assess patients' behavior and investigate the acceptance of our personal authorization-controlled framework.

Results: The constructed iWellChain Framework was installed in an affiliated teaching hospital and four collaborative clinics. The framework renders all medical referral processes automatic and paperless and facilitates efficient NHIA reimbursements. In addition, the blockchain-enabled iWellChain DApp was distributed for patients to access and control their EMR and EHR data. Analysis of 3 months (September to December 2018) of access logs revealed that patients were highly interested in acquiring health data, especially those of laboratory test reports.

Conclusions: This study is a pioneer of blockchain applications for medical referral services, and the constructed framework and DApp have been applied practically in clinical settings. The iWellChain Framework has the scalability to deploy a blockchain environment effectively for health care facilities; the iWellChain DApp has potential for use with more patient-centered applications to collaborate with the industry and facilitate its adoption.
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http://dx.doi.org/10.2196/13563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920914PMC
December 2019

Cytarabine-Resistant -ITD Leukemia Cells are Associated with Mutation and Multiple Pathway Alterations-Possible Therapeutic Efficacy of Cabozantinib.

Int J Mol Sci 2019 Mar 11;20(5). Epub 2019 Mar 11.

Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.

Internal tandem duplication of FLT3 juxtamembrane domain (FLT3-ITD)-positive acute myeloid leukemia (AML) leads to poor clinical outcomes after chemotherapy. We aimed to establish a cytarabine-resistant line from -ITD-positive MV4-11 (MV4-11-P) cells and examine the development of resistance. The -ITD mutation was retained in MV4-11-R; however, the protein was underglycosylated and less phosphorylated in these cells. Moreover, the phosphorylation of ERK1/2, Akt, MEK1/2 and p53 increased in MV4-11-R. The levels of Mcl-1 and p53 proteins were also elevated in MV4-11-R. A p53 D281G mutant emerged in MV4-11-R, in addition to the pre-existing R248W mutation. MV4-11-P and MV4-11-R showed similar sensitivity to cabozantinib, sorafenib, and MK2206, whereas MV4-11-R showed resistance to CI-1040 and idarubicin. MV4-11-R resistance may be associated with inhibition of Akt phosphorylation, but not ERK phosphorylation, after exposure to these drugs. The multi-kinase inhibitor cabozantinib inhibited FLT3-ITD signaling in MV4-11-R cells and MV4-11-R-derived tumors in mice. Cabozantinib effectively inhibited tumor growth and prolonged survival time in mice bearing MV4-11-R-derived tumors. Together, our findings suggest that Mcl-1 and Akt phosphorylation are potential therapeutic targets for p53 mutants and that cabozantinib is an effective treatment in cytarabine-resistant FLT3-ITD-positive AML.
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http://dx.doi.org/10.3390/ijms20051230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429333PMC
March 2019

Chitosan Inhibits the Rehabilitation of Damaged Microbes Induced by Photodynamic Inactivation.

Int J Mol Sci 2018 Sep 1;19(9). Epub 2018 Sep 1.

Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan.

Previously, we showed that chitosan could augment the biocidal efficacy mediated by photodynamic treatment against , , and . In this study, we showed that the antimicrobial action of chitosan in augmenting photodynamic inactivation (PDI) is related to the increase in cell surface destruction. The microbial cell surfaces exhibit severe irregular shapes after PDI in the presence of chitosan as demonstrated by transmitted electron microscopy. Furthermore, increases in the concentration or incubation time of chitosan significantly reduced the amounts of photosensitizer toluidine blue O required, indicating that chitosan could be an augmenting agent used in conjunction with PDI against , , and . A prolonged lag phase was found in microbial cells that survived to PDI, in which chitosan acted to completely eradicate the cells. Once the exponential log stage and cell rebuild began, their cellular functions from PDI-induced damage returned and the increased cytotoxic effect of chitosan disappeared. Together, our results suggest that chitosan can prevent the rehabilitation of PDI-surviving microbial cells, leading to increased biocidal efficacy.
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http://dx.doi.org/10.3390/ijms19092598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164787PMC
September 2018

CD40-mediated HIF-1α expression underlying microangiopathy in diabetic nerve pathology.

Dis Model Mech 2018 04 26;11(4). Epub 2018 Apr 26.

Department of Anatomy and Cell Biology, National Taiwan University, Taipei 10051, Taiwan

To understand the pathology and molecular signatures of microangiopathy in diabetic neuropathy, we systemically and quantitatively examined the morphometry of microvascular and nerve pathologies of sural nerves. In the endoneurium of diabetic nerves, prominent microangiopathy was observed, as evidenced by reduced capillary luminal area, increased capillary basement membrane thickness and increased proportion of fibrin(+) blood vessels. Furthermore, capillary basement membrane thickness and the proportion of fibrin(+) blood vessels were correlated with small myelinated fiber density in diabetic nerves. In diabetic nerves, there was also significant macrophage and T cell infiltration, and cluster of differentiation 40 (CD40) expression was increased. The molecular alterations observed were upregulation of hypoxia-inducible factor-1α (HIF-1α), mitogen-activated protein kinase-activated protein kinase 2 (MK2; MAPKAPK2) and phosphatase and tensin homolog (PTEN). In addition, HIF-1α was correlated with small myelinated fiber density and capillary luminal area, while both MK2 and PTEN were correlated with capillary basement membrane thickness. The molecular cascades were further demonstrated and replicated in a cell model of microangiopathy on human umbilical vein endothelial cells (HUVECs) exposed to high-glucose medium by silencing of CD40, PTEN and HIF-1α in HUVECs using shRNA. These data clarified the hierarchy of the molecular cascades, i.e. upregulation of CD40 leading to HIF-1α expression in endothelium and nerve fibers. In conclusion, this study revealed the association of microangiopathy, thrombosis and inflammatory infiltrates with nerve degeneration in diabetic nerves, demonstrating that CD40 is a key molecule for the upregulation of HIF-1α and PTEN underlying the severity of microangiopathy.
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http://dx.doi.org/10.1242/dmm.033647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963861PMC
April 2018

cAMP receptor protein regulates mouse colonization, motility, fimbria-mediated adhesion, and stress tolerance in uropathogenic Proteus mirabilis.

Sci Rep 2017 08 4;7(1):7282. Epub 2017 Aug 4.

Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.

Cyclic AMP receptor protein (Crp) is a major transcriptional regulator in bacteria. This study demonstrated that Crp affects numerous virulence-related phenotypes, including colonization of mice, motility, fimbria-mediated adhesion, and glucose stress tolerance in uropathogenic Proteus mirabilis. Diabetic mice were more susceptible to kidney colonization by wild-type strain than nondiabetic mice, in which the crp mutant exhibited increased kidney colonization. Loss of crp or addition of 10% glucose increased the P. mirabilis adhesion to kidney cells. Direct negative regulation of pmpA (which encodes the major subunit of P-like fimbriae) expression by Crp was demonstrated using a reporter assay and DNase I footprinting. Moreover, the pmpA/crp double mutant exhibited reduced kidney adhesion comparable to that of the pmpA mutant, and mouse kidney colonization by the pmpA mutant was significantly attenuated. Hence, the upregulation of P-like fimbriae in the crp mutant substantially enhanced kidney colonization. Moreover, increased survival in macrophages, increased stress tolerance, RpoS upregulation, and flagellum deficiency leading to immune evasion may promote kidney colonization by the crp mutant. This is the first study to elucidate the role of Crp in the virulence of uropathogenic P. mirabilis, underlying mechanisms, and related therapeutic potential.
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http://dx.doi.org/10.1038/s41598-017-07304-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544767PMC
August 2017

Risk factors for complications following immediate tissue expander based breast reconstruction in Taiwanese population.

J Formos Med Assoc 2017 Jan 2;116(1):57-63. Epub 2016 Mar 2.

Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Division of Plastic Surgery, Department of Surgery, Taipei Medical University Hospital and College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Background/purpose: Breast cancer patients in Asia show considerable disparities from Caucasian patients, such as younger age of onset and lower rates of smoking, obesity, and diabetes. Findings of prior studies regarding risk factors associated with complications in tissue expander may not hold for Asian populations, since most of these studies involved Caucasian patients. In this study, we surveyed risk factors in the Taiwanese population, providing additional evidence about the important differences and discuss the implications for clinical practice.

Methods: Patients who underwent immediate, two-stage, tissue expander breast reconstruction from December 2008 to August 2014 in the National Taiwan University Hospital, Taipei, Taiwan were included. Follow-up observations of all patients were conducted until December 2014. Complications occurring during the tissue expander stage were evaluated. Multivariate regression modeling was used to identify risk factors for complications.

Results: A total of 246 consecutive, immediate, smooth round tissue expander placements were performed for breast reconstruction. The most common complication was skin necrosis (4.9%), followed by wound dehiscence (4.1%). In the multivariate model, body mass index (BMI) ≥ 24 kg/m was the only risk factor that reached statistical significance (odds ratio: 2.41, 95% confidence interval: 1.17-4.96).

Conclusion: We provided evidence that racial disparities have an impact on the risk factors for complications associated with tissue expander breast reconstruction. BMI≥24 kg/m was the only risk factor significantly associated with complications. Clinically, BMI≥24 kg/m, rather than the standard definition of obesity (BMI > 30 kg/m), may be a more suitable cutoff point for risk in patients of Asian ethnicity.
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http://dx.doi.org/10.1016/j.jfma.2016.01.012DOI Listing
January 2017

Postoperative Showering for Clean and Clean-contaminated Wounds: A Prospective, Randomized Controlled Trial.

Ann Surg 2016 May;263(5):931-6

*Department of Nursing, National Taiwan University College of Medicine, Taipei, Taiwan †Department of Surgery, National Taiwan University College of Medicine, Taipei, Taiwan ‡Institute of Statistical Science, Academia Sinica, National Taiwan University College of Medicine, Taipei, Taiwan §Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan ¶Department of Medical Research, National Taiwan University College of Medicine, Taipei, Taiwan ||Department of Traumatology, National Taiwan University College of Medicine, Taipei, Taiwan **School of Nursing, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Objective: To evaluate wound infection rates, pain scores, satisfaction with wound care, and wound care costs starting 48 hours after surgery.

Background: Showering after surgery is a controversial issue for wound care providers and patients. We investigated the benefits and detriments of showering for postoperative wound care.

Methods: Patients undergoing thyroid, lung, inguinal hernia, and face and extremity surgeries with clean or clean-contaminated wounds were included. The patients were randomized to allow showering (shower group) or to keep the wound dry (nonshower group) for postoperative wound care starting 48 hours after surgery. The primary endpoint was the rate of surgical wound infection. The secondary endpoints included the wound pain score, satisfaction with wound care, and cost of wound care.

Results: Between May 2013 and March 2014, there were 222 patients randomized to the shower group and 222 to the nonshower group. Two patients in each group were lost to follow-up. There were 4 superficial surgical site infections in the shower group and 6 in the nonshower group (4/220, 1.8% vs 6/220, 2.7%, P = 0.751). Postoperative pain scores were comparable between the 2 groups. Patients in the shower group were more satisfied with their method of wound care, and their wound care costs were lower when compared with the nonshower group.

Conclusions: Clean and clean-contaminated wounds can be safely showered 48 hours after surgery. Postoperative showering does not increase the risk of surgical site complications. It may increase patients' satisfaction and lower the cost of wound care.
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http://dx.doi.org/10.1097/SLA.0000000000001359DOI Listing
May 2016

Treatment and long-term follow-up of oral cancer postoperative sialorrhea with dermal sling operation.

Ann Plast Surg 2015 May;74 Suppl 2:S113-7

From the Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

Introduction: Reconstruction of a full-thickness defect that includes oral commissure presents a considerable challenge to maxillofacial and plastic surgeons. The goals of reconstruction are both functional and cosmetic. Sialorrhea, or drooling, is a major problem after flap reconstruction and influences the quality of life of the patient. In this article, we report on our experience performing a dermal sling operation to treat postoperative sialorrhea in patients with oral cancer.

Materials And Methods: Preoperative and postoperative levels of sialorrhea were evaluated based on the Drooling Severity and Frequency Scale. Dermal sling operations were performed on 27 patients from January 2000 to December 2013. In these patients, 12 cases were reviewed and followed up over 1 year.

Results: Of the 12 patients, 11 were men and one was a woman, with the mean age of 58 years (range, 40-79 years). There were no operative complications. The mean preoperative score was 4.75 (range, 3-7), and the mean postoperative score was 3.83 (range, 2-5). This change was significant (P=0.005), with valuation with the Wilcoxon signed rank test. The mean time of follow-up was 3.5 years (range, 1.1-7.7 years).

Conclusions: The dermal sling operation is an acceptable treatment for postoperative sialorrhea in patients with commissure-involved oral cancer.
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http://dx.doi.org/10.1097/SAP.0000000000000466DOI Listing
May 2015

Clinical Application of Different Surgical Navigation Systems in Complex Craniomaxillofacial Surgery: The Use of Multisurface 3-Dimensional Images and a 2-Plane Reference System.

Ann Plast Surg 2016 Apr;76(4):411-9

From the Department of Surgery, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Background: Intraoperative navigation is a tool that provides surgeons with real-time guidance based on patients' preoperative imaging studies. The application of intraoperative navigation to neurosurgery and otolaryngology has been well documented; however, only isolated reports have analyzed its potential in the field of craniomaxillofacial surgery.

Methods: From November 2010 to July 2014, 15 patients were operated on for complex craniomaxillofacial surgery with assistance by 3 different navigation systems, which used either infrared or electromagnetic technologies. We imported fine-cut (0.625-mm) computed tomographic scan images of the patients to the navigation systems whose software processed them into multisurface 3-dimentional models used as guiding material for the surgical navigation. We also developed a simple "2-plane reference system" to ensure that the final results were symmetric to the normal half of the face. Appearance outcome was evaluated by questionnaire.

Results: Of these 15 cases, 3 cases were performed with infrared-based navigation, and the remaining 12 cases were accomplished by electromagnetic technology. Most of these cases resulted in satisfactory outcomes after tumor resection, posttraumatic reconstruction, and postablative reconstruction.

Conclusion: Navigation systems offer highly valuable intraoperative assistance in complex craniomaxillofacial surgery. Not only can these systems pinpoint deep-seated lesions as neurosurgeons or otolaryngologists do, but they can also use a simple 2-plane reference system for accurate bone alignment. Moreover, advancements in multisurface 3-D models provide us more reliable intuitive image guidance. The application of electromagnetic technology, with its smaller reference obviation of the line-of-sight problem, makes the manipulation of craniomaxillofacial surgery more comfortable.
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http://dx.doi.org/10.1097/SAP.0000000000000429DOI Listing
April 2016

Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden.

PLoS One 2014 31;9(12):e115916. Epub 2014 Dec 31.

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Genetics National Taiwan University Hospital, Taipei, Taiwan.

Neurofibromatosis type 1 (NF1) is the most common tumor predisposition disorder affecting 1/3500 worldwide. Patients are at risk of developing benign (neurofibromas) and malignant peripheral nerve sheath tumors (MPNST). The AXL receptor tyrosine kinase has been implicated in several kinds of cancers, but so far no studies have investigated the role of AXL in NF1 related tumorigenesis. Recently, the soluble fraction from the extracellular domain of AXL (sAXL) has been found in human plasma, and its level was correlated to poor prognosis in patients with renal cancer. Compared to normal human Schwann cells, a significantly high expression level of AXL was found in three of the four MPNST cell lines and two of the three primary MPNST tissues. Similarly, the level of sAXL in conditioned media corresponded to the protein and mRNA levels of AXL in the MPNST cell lines. Furthermore, in two different human MPNST xenograft models, the human sAXL could be detected in the mouse plasma. Its level was proportionate to the size of the xenograft tumors, while no human sAXL was detect prior to the formation of the tumors. Treatment with a newly developed photodynamic therapy, prevented further tumor growth and resulted in drastically reduced the levels of sAXL compared to that of the control group. Finally, the level of sAXL was significantly increased in patients with plexiform tumors compared to patients with only dermal neurofibromas, further supporting the role of sAXL as a marker for NF1 related tumor burden.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115916PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281253PMC
October 2015

New aspects of RpoE in uropathogenic Proteus mirabilis.

Infect Immun 2015 Mar 29;83(3):966-77. Epub 2014 Dec 29.

Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China

Proteus mirabilis is a common human pathogen causing recurrent or persistent urinary tract infections (UTIs). The underlying mechanisms for P. mirabilis to establish UTIs are not fully elucidated. In this study, we showed that loss of the sigma factor E (RpoE), mediating extracytoplasmic stress responses, decreased fimbria expression, survival in macrophages, cell invasion, and colonization in mice but increased the interleukin-8 (IL-8) expression of urothelial cells and swarming motility. This is the first study to demonstrate that RpoE modulated expression of MR/P fimbriae by regulating mrpI, a gene encoding a recombinase controlling the orientation of MR/P fimbria promoter. By real-time reverse transcription-PCR, we found that the IL-8 mRNA amount of urothelial cells was induced significantly by lipopolysaccharides extracted from rpoE mutant but not from the wild type. These RpoE-associated virulence factors should be coordinately expressed to enhance the fitness of P. mirabilis in the host, including the avoidance of immune attacks. Accordingly, rpoE mutant-infected mice displayed more immune cell infiltration in bladders and kidneys during early stages of infection, and the rpoE mutant had a dramatically impaired ability of colonization. Moreover, it is noteworthy that urea (the major component in urine) and polymyxin B (a cationic antimicrobial peptide) can induce expression of rpoE by the reporter assay, suggesting that RpoE might be activated in the urinary tract. Altogether, our results indicate that RpoE is important in sensing environmental cues of the urinary tract and subsequently triggering the expression of virulence factors, which are associated with the fitness of P. mirabilis, to build up a UTI.
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http://dx.doi.org/10.1128/IAI.02232-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333446PMC
March 2015

CD200 in growing rat lungs: developmental expression and control by dexamethasone.

Cell Tissue Res 2015 Mar 19;359(3):729-42. Epub 2014 Dec 19.

Department of Anatomy, China Medical University, Taichung, 404, Taiwan.

CD200 belongs to cell adhesion molecules of the immunoglobulin superfamily. It lacks intracellular signaling motifs and exerts immunosuppressive effect in various tissues. We have reported previously that CD200 is predominantly associated with the capillary network in the alveolar septum of adult rats. The alveolar endothelial cells express CD200, which is confined to their luminal cell membrane facing the blood-air barrier. Our present results show that lung CD200 protein increases gradually with advancing age, being maximally expressed in the early postnatal (P) period. CD200 protein expression, however, declines at P5 but increases again after P7, reaching the adult level at P21. In developing lungs in fetal and neonatal stages, double-immunofluorescence staining has confirmed intense CD200 immunoreactivity delineating the vascular profiles in the double layers of the alveolar capillaries; this staining becomes diffuse and patchy with time. Unlike in adult lungs, immunoelectron microscopy has revealed that CD200 expression in fetal and early postnatal lungs is localized over the entire luminal cell membrane and in the cytoplasm of the endothelia. CD200 expression is progressively redistributed to a specific luminal domain of alveolar endothelia during pulmonary microvascular maturation. In neonatal rats treated with dexamethasone, the amount of lung CD200 significantly increases and is also elevated with time. Upregulation of endothelial CD200 has further been confirmed in isolated pulmonary microvascular endothelial cells treated with dexamethasone. Thus, lung CD200 is developmentally regulated, possibly under hormonal influence.
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http://dx.doi.org/10.1007/s00441-014-2065-8DOI Listing
March 2015

Blastocystis hominis infection in a post-cardiotomy patient on extracorporeal membrane oxygenation support: A case report and literature review.

Int J Surg Case Rep 2014 2;5(9):637-9. Epub 2014 Aug 2.

Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address:

Introduction: Opportunistic pathogens can cause severe damage leading to irreversible complications in immune-compromised patients. Here we describe a patient who sustained Blastocystis hominis infection resulting in severe sepsis while on extracorporeal membrane oxygenation (ECMO) support, and the course of treatment taken to treat him.

Presentation Of Case: Our case, a 34-year-old Filipino man, was hospitalized for valvular disease and received valve replacements. ECMO and an intra-aortic balloon pump (IABP) were implemented when the patient developed progressive heart failure after cardiac surgery. Unfortunately, the patient suffered from sepsis with persistent fever and diarrhea, and subsequent examinations indicated the patient was infected by B. hominis. After adequate administration of the antibiotic metronidazole, the patient's symptoms subsided and he was discharged.

Discussion: Blastocystis hominis is a unicellular protozoa commonly found in the intestinal tract, and the prevalence of B. hominis is 1.5-10% in developed countries and 30-50% in developing countries. The patient needed the support of ECMO and IABP, was immunocompromised to a certain extent; B. hominis can be a harmful opportunistic pathogen for them and lead to severe irreversible complications such as death.

Conclusion: This is the first published article showing that the opportunistic pathogen, B. hominis, can cause severe infection in patients on ECMO support, a result that should be kept in mind when patients come from a place with a high prevalence of B. hominis. The prophylactic medication should be administered routinely when patients live in the region and extracorporeal life-support is used.
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http://dx.doi.org/10.1016/j.ijscr.2014.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200881PMC
September 2014

Reconstruction for osteoradionecrosis of the mandible: superiority of free iliac bone flap to fibula flap in postoperative infection and healing.

Ann Plast Surg 2014 Sep;73 Suppl 1:S18-26

From the *Christine M. Kleinert Institute for Hand and Microsurgery, Louisville, KY; †Department of Plastic Surgery, China Medical University Hospital, Taichung City; and ‡Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.

Background: Osteoradionecrosis (ORN) of the mandible is not an uncommon complication after radiotherapy for head and neck cancers. Although definitive treatment has been confirmed as radical excision of the necrotic bone with simultaneous vascularized osteocutaneous flap reconstruction, it remains a unique challenge. In this study, we compare our results of reconstruction with free iliac and fibula flaps in flap survival, bony union, and postoperative complications.

Patients And Methods: From 1986 to 2011, there were 153 mandibular ORN cases in our center that were treated with radical resection of the necrotic bone and reconstruction with either vascularized iliac (n=108) or fibula flaps (n=45). Data collected for analysis included patient demographics, flap survival rate, postoperative infection rate, nonunion/malunion rate, mean hospital stay, and antibiotics use.

Results: All patients healed eventually without recurrence of ORN. However, we observed difference in the complication rate between the iliac flap group and fibula flap group. In the group with iliac flap reconstruction, patients required less days of hospital stay for intravenous antibiotics treatment postoperatively. The average days required for intravenous antibiotics in the iliac flap group were 10.46 (2.28) versus 16.09 (3.88) days in the fibula group (P<0.01). In the group with fibula flap reconstruction, 9 (20.0%) patients had subsequent neck infection due to healing problem, compared to 8 (7.4%) patients in the iliac flap group (P=0.04). In the iliac flap group, the nonunion and malunion rates were 4.6% and 2.8% respectively; whereas in the fibula group, the rates were 15.5% and 6.6%, respectively (P=0.04 and 0.36, respectively).

Conclusions: For ORN patients, vascularized iliac bone flap provides more reliable results compared to fibula flap. The merits of vascularized iliac flap include the following: (1) its natural curve mimics the shape of mandible and does not need osteotomy; (2) it offers more volume of bone that matches better to the native mandible to allow later osteointegration as well as faster bony union, due to the nature of being a membranous bone; and (3) it carries more abundant soft tissue to obliterate possible dead space. The only disadvantages are short pedicle and requiring special management of skin paddle, which can be overcome by training in microsurgery.
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http://dx.doi.org/10.1097/SAP.0000000000000270DOI Listing
September 2014

The RNA chaperone Hfq is involved in stress tolerance and virulence in uropathogenic Proteus mirabilis.

PLoS One 2014 15;9(1):e85626. Epub 2014 Jan 15.

Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China ; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.

Hfq is a bacterial RNA chaperone involved in the riboregulation of diverse genes via small noncoding RNAs. Here, we show that Hfq is critical for the uropathogenic Proteus mirabilis to effectively colonize the bladder and kidneys in a murine urinary tract infection (UTI) model and to establish burned wound infection of the rats. In this regard, we found the hfq mutant induced higher IL-8 and MIF levels of uroepithelial cells and displayed reduced intra-macrophage survival. The loss of hfq affected bacterial abilities to handle H2O2 and osmotic pressures and to grow at 50 °C. Relative to wild-type, the hfq mutant had reduced motility, fewer flagella and less hemolysin expression and was less prone to form biofilm and to adhere to and invade uroepithelial cells. The MR/P fimbrial operon was almost switched to the off phase in the hfq mutant. In addition, we found the hfq mutant exhibited an altered outer membrane profile and had higher RpoE expression, which indicates the hfq mutant may encounter increased envelope stress. With the notion of envelope disturbance in the hfq mutant, we found increased membrane permeability and antibiotic susceptibilities in the hfq mutant. Finally, we showed that Hfq positively regulated the RpoS level and tolerance to H2O2 in the stationary phase seemed largely mediated through the Hfq-dependent RpoS expression. Together, our data indicate that Hfq plays a critical role in P. mirabilis to establish UTIs by modulating stress responses, surface structures and virulence factors. This study suggests Hfq may serve as a scaffold molecule for development of novel anti-P. mirabilis drugs and P. mirabilis hfq mutant is a vaccine candidate for preventing UTIs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085626PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893223PMC
December 2014

Patient-centered wound teleconsultation for cutaneous wounds: a feasibility study.

Ann Plast Surg 2014 Feb;72(2):220-4

From the *Department of Surgery, National Taiwan University Hospital and College of Medicine; †Institute of Biomedical Engineering, National Taiwan University, Taipei; ‡National Taiwan University Hospital Yun-Lin Branch, Yun-Lin; and §National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.

Introduction: The purpose of this study was to investigate the feasibility of patient-centered teleconsultation for various cutaneous wounds by using store-and-forward technology.

Materials And Methods: From July 2011 to November 2011, 53 patients with various wound conditions were enrolled in this study. The patients took their own wound images shortly before face-to-face consultations with a plastic surgeon, and the images were sent via e-mail to another 3 remote plastic surgeons along with brief medical information. All 4 surgeons completed a standard questionnaire individually, which addressed questions regarding the presence of wound conditions (gangrene, necrosis, erythema, and cellulitis/infection), as well as suggested clinical treatment with antibiotics and debridement. The evaluations were compared among the 3 remote surgeons as well as the remote and onsite surgeons.

Results: The 53 wounds included in our study exhibited different causative mechanisms and locations on the body. The concordances between the remote and onsite surgeons were 92%, 79%, 83%, and 85% regarding the presence of gangrene, necrosis, erythema, and cellulitis/infection, respectively. The agreement rates regarding the treatment suggestion with antibiotic use and debridement between the remote surgeons and the onsite surgeon were both 83%. The remote surgeons reported high specificity, at least 84%, in all parameters of wound descriptions or treatment suggestions.

Conclusions: The patient-centered teleconsultation system based on store-and-forward technology is a feasible tool for wound management, and it shows promises in future clinical applications by decreasing clinic visits.
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http://dx.doi.org/10.1097/SAP.0000000000000031DOI Listing
February 2014

A modified free chimeric osteocutaneous fibular flap design for head and neck reconstruction: experience on a series of 10 cases.

Microsurgery 2013 Sep 29;33(6):439-46. Epub 2013 Jul 29.

Division of Plastic Surgery, Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan.

Background: We have previously described a modified chimeric fibular osteocutaneous flap design based on a combination of a traditional fibular flap and a peroneal artery perforator fasciocutaneous flap for mandible and adjacent soft tissue reconstruction. The purpose of this article is to share our experience with a larger case series utilizing this new technique for mandible and adjacent soft tissue reconstruction after cancer wide excision surgery and a more detailed description on these flaps harvesting procedures.

Patients And Methods: Ten patients (age range from 32 to 63 years), who had segmental defect of mandible and adjacent soft tissue defect after cancer wide excision surgery, received mandible and adjacent soft tissue reconstruction based on the modified chimeric fibular flap design.

Results: The skin paddle based on peroneal perforators ranged from 9 cm × 3.5 cm to 10 cm × 10 cm and the mean pedicle length was 8.9 cm. Four patients underwent primary closure of the donor site. Three flap salvage procedures were performed due to vascular thrombosis and all flaps survived well. Nine patients had acceptable outer appearance, and one patient complained of cheek sunken. All patients had at least 3-cm interincisor distance during a mean of 12-month follow-up period.

Conclusion: The modified chimeric osteocutaneous fibula flaps were feasible design with few intermuscular septum problems during bone fixation. Furthermore, it provided larger skin paddles with few restrictions to reconstruct the cheek skin defect.
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http://dx.doi.org/10.1002/micr.22123DOI Listing
September 2013

The use of Chitosan to enhance photodynamic inactivation against Candida albicans and its drug-resistant clinical isolates.

Int J Mol Sci 2013 Apr 3;14(4):7445-56. Epub 2013 Apr 3.

Department of Surgery, National Taiwan University College of Medicine, Taipei 100, Taiwan.

Drug-resistant Candida infection is a major health concern among immunocompromised patients. Antimicrobial photodynamic inactivation (PDI) was introduced as an alternative treatment for local infections. Although Candida (C.) has demonstrated susceptibility to PDI, high doses of photosensitizer (PS) and light energy are required, which may be harmful to eukaryotic human cells. This study explores the capacity of chitosan, a polycationic biopolymer, to increase the efficacy of PDI against C. albicans, as well as fluconazole-resistant clinical isolates in planktonic or biofilm states. Chitosan was shown to effectively augment the effect of PDI mediated by toluidine blue O (TBO) against C. albicans that were incubated with chitosan for 30 min following PDI. Chitosan at concentrations as low as 0.25% eradicated C. albicans; however, without PDI treatment, chitosan alone did not demonstrate significant antimicrobial activity within the 30 min of incubation. These results suggest that chitosan only augmented the fungicidal effect after the cells had been damaged by PDI. Increasing the dosage of chitosan or prolonging the incubation time allowed a reduction in the PDI condition required to completely eradicate C. albicans. These results clearly indicate that combining chitosan with PDI is a promising antimicrobial approach to treat infectious diseases.
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http://dx.doi.org/10.3390/ijms14047445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645695PMC
April 2013

Photodynamic inactivation of chlorin e6-loaded CTAB-liposomes against Candida albicans.

Lasers Surg Med 2013 Mar;45(3):175-85

Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan.

Background And Objectives: Antimicrobial photodynamic inactivation (PDI) is a promising therapeutic modality for the treatment of local infections. To increase the efficacy of PDI, chlorine e6 (Ce6) was encapsulated in cationic CTAB-liposomes composed of various ratios of dimyristoyl-sn-glycero-phosphatidylcholine (DMPC) and the cationic surfactant, cetyltrimethyl ammonium bromide (CTAB). The PDI efficacy of the liposomal-Ce6 was assessed in vitro against susceptible and drug-resistant clinical isolates of Candida albicans (C. albicans) as well as in infected burn wounds.

Study Design/materials And Methods: Ce6 was encapsulated in CTAB-liposomes by the film hydration method. Particle size distribution and zeta potential of the cationic liposomes were measured using a Zetasizer Nano-ZS. UV-visible spectra were used to measure lipid/Ce6 (L/C) ratio and drug entrapment efficiency while differential scanning calorimetry (DSC) was used to study the thermotropic behavior of DMPC liposomes upon CTAB addition. In vivo PDI efficacy was carried out in an infected burn wound using a rat model.

Results: The increase in zeta potential and a shift in the phase transition temperature (Tm ) upon CTAB addition confirmed its entrapment within the lipid bilayers of the liposome. Meanwhile, the CTAB addition did not affect the Ce6 entrapment efficiency and physical attributes of the liposomes. In vitro studies showed that the PDI effect of the Ce6-loaded CTAB-liposomes was dependent on the lipid to Ce6 molar ratio (L/C), particle size and the concentration of CTAB in the liposomes. The lower L/C ratio and smaller liposomes exerted significantly higher PDI effects. In addition, an increase in the CTAB to lipid ratio led to a significant increase in the PDI effect of Ce6 against susceptible and drug-resistant clinical isolates of C. albicans after light illumination.

Conclusions: Our results indicate that a low L/C ratio, high positive charge, and small particle size of CTAB-liposomes significantly enhances their PDI efficacy against C. albicans.
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http://dx.doi.org/10.1002/lsm.22124DOI Listing
March 2013

Thalidomide inhibits fibronectin production in TGF-β1-treated normal and keloid fibroblasts via inhibition of the p38/Smad3 pathway.

Biochem Pharmacol 2013 Jun 13;85(11):1594-602. Epub 2013 Mar 13.

Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taiwan.

Keloids are characterized by the vigorously continuous production of extracellular matrix protein and aberrant cytokine activity in the dermis. There is a growing body of evidence that thalidomide, α-N-phthalimidoglutarimide, has anti-fibrotic properties. The aims were to examine possible therapeutic effects of thalidomide on fibronectin expression in transforming growth factor-β1 (TGF-β1)-treated normal fibroblasts (NFs) and keloid-derived fibroblasts (KFs) and the underlying mechanism of action, especially the involvement of mitogen-activated protein kinase (MAPKs) and Sma- and Mad-related family (Smads) pathways. In surgically removed human tissues, TGF-β1 and fibronectin immunoreactivity was high in keloid tissue, but barely detectable in normal tissue. TGF-β1 induced significant fibronectin expression in NFs and KFs and the effect was inhibited by pretreatment with thalidomide. TGF-β1 also induced phosphorylation of MAPKs (ERK1/2, p38, and JNK) and Smad2/3 and pretreatment with PD98059 (an ERK1/2 inhibitor), SB203580 (a p38 inhibitor), or SP600125 (a JNK inhibitor) inhibited TGF-β1-induced fibronectin expression. Furthermore, pretreatment with thalidomide inhibited the TGF-β1-induced phosphorylation of p38 and Smad3, but not that of ERK1/2, JNK, and Smad2. In addition, thalidomide pretreatment inhibited the TGF-β-induced DNA binding activity of AP-1 and Smad3/4, caused fibronectin degradation by increasing the activity of matrix metalloproteinase 9, and decreased production of TGF-β1 and fibronectin and the number of fibroblasts in an in vivo keloid model. These results show that thalidomide has an antifibrotic effect on keloid fibroblasts that is caused by suppression of TGF-β1-induced p38 and Smad3 signaling. Our findings indicate that thalidomide may be a potential candidate drug for the treatment and prevention of keloids.
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http://dx.doi.org/10.1016/j.bcp.2013.02.038DOI Listing
June 2013

Compression neuropathy of the ulnar digital nerves in the thumbs of a massage therapist.

Ann Plast Surg 2014 ;72(6):649-51

From the Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan.

Compression neuropathies of digital nerves, caused by hypertrophied or anomalous muscles, are rare compared with such occurrences above the wrist. We reported a case of compression neuropathy of the ulnar digital nerves in bilateral thumbs of a massage therapist. Entrapment of the digital nerves by the hypertrophied first dorsal interosseous and adductor pollicis muscles over the first web space of the right hand was detected by magnetic resonance imaging. Surgical debulking of the muscles and neurolysis were performed on the dominant right hand. The left hand was successfully treated with botulinum toxin. No recurrence was noted in a follow-up of 36 months.
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http://dx.doi.org/10.1097/SAP.0b013e31826a1607DOI Listing
January 2015

Chloride intracellular channel 4 involves in the reduced invasiveness of cancer cells treated by photodynamic therapy.

Lasers Surg Med 2013 Jan 15;45(1):38-47. Epub 2013 Jan 15.

Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan.

Background And Objectives: The mechanisms of photodynamic therapy (PDT) have been studied on the cellular and tissue levels. However, the cellular behaviors of cancer cells survived from PDT are still not clear. Previously, we have found that PDT-derived variants A375/3A5 and A375/6A5 have reduced invasion ability. This study attempted to further elucidate the possible molecules associated with the altered invasiveness in the PDT-derived variants and cancer cells treated with PDT.

Study Design/materials And Methods: Scratch wound healing assay and invasion assay were performed to evaluate the migration and invasion ability of human A375 melanoma and MDA-MB-231 breast adenocarcinoma cells. Single colony selection and microarray analysis were performed to examine the differentially expressed transcripts in parental A375 and PDT-derived variants. RT-PCR and Western blots analysis were performed to examine the expression levels of matrix metalloproteinase 9 (MMP9) and chloride intracellular channel 4 (CLIC4). The MMP9 activity was examined by Zymography assay. CLIC4 expressing construct was used to examine the influence on MMP9 expression and invasion ability of cancer cells treated with PDT.

Results: Correlated with the reduced invasiveness, we found that A375/3A5 and A375/6A5 cells have decreased production of MMP9. Microarray analysis and RT-PCR showed CLIC4 was down-regulated in the PDT-derived variants. Furthermore, down-regulation of CLIC4 and MMP9 was found in cancer cells treated with PDT. Transfection of surviving cancer cells with a plasmid vector encoding CLIC4 increased MMP9 expression and cell invasion. Furthermore, overexpression of CLIC4 in A375 and MDA-MB-231 cancer cells constrains PDT-induced suppression of invasiveness.

Conclusion: Our results showed that the reduced expression of CLIC4 could further down-regulate MMP9 and result in the suppression of invasion in cancer cells treated with PDT. These results provide an insight into a new mechanism by which PDT affects the metastatic potential of cancer cells through down-regulation of MMP9 by CLIC4.
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http://dx.doi.org/10.1002/lsm.22112DOI Listing
January 2013

10'(Z),13'(E)-heptadecadienylhydroquinone inhibits swarming and virulence factors and increases polymyxin B susceptibility in Proteus mirabilis.

PLoS One 2012 20;7(9):e45563. Epub 2012 Sep 20.

Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan, Republic of China.

In this study, we demonstrated that 10'(Z), 13'(E)-heptadecadienylhydroquinone (HQ17-2), isolated from the lacquer tree, could decrease swarming motility and hemolysin activity but increase polymyxin B (PB) susceptibilityof Proteus mirabilis which is intrinsically highly-resistant to PB. The increased PB susceptibility induced by HQ17-2 was also observed in clinical isolates and biofilm-grown cells. HQ17-2 could inhibit swarming in the wild-type and rppA mutant but not in the rcsB mutant, indicating that HQ17-2 inhibits swarming through the RcsB-dependent pathway, a two-component signaling pathway negatively regulating swarming and virulence factor expression. The inhibition of hemolysin activity by HQ17-2 is also mediated through the RcsB-dependent pathway, because HQ17-2 could not inhibit hemolysin activity in the rcsB mutant. Moreover, the finding that HQ17-2 inhibits the expression of flhDC gene in the wild-type and rcsB-complemented strain but not in the rcsB mutant supports the notion. By contrast, HQ17-2 could increase PB susceptibility in the wild-type and rcsB mutant but not in the rppA mutant, indicating that HQ17-2 increases PB susceptibility through the RppA-dependent pathway, a signaling pathway positively regulating PB resistance. In addition, HQ17-2 could inhibit the promoter activities of rppA and pmrI, a gene positively regulated by RppA and involved in PB resistance, in the wild-type but not in the rppA mutant. The inhibition of rppA and pmrI expression caused lipopolysaccharide purified from HQ17-2-treated cells to have higher affinity for PB. Altogether, this study uncovers new biological effects of HQ17-2 and provides evidence for the potential of HQ17-2 in clinical applications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0045563PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447793PMC
March 2013

Antioxidant sol-gel improves cutaneous wound healing in streptozotocin-induced diabetic rats.

Exp Diabetes Res 2012 7;2012:504693. Epub 2012 Aug 7.

Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan.

We examined the effects of vitamin C in Pluronic F127 on diabetic wound healing. Full-thickness excision skin wounds were made in normal and diabetic Wistar rats to evaluate the effect of saline, saline plus vitamin C (antioxidant sol), Pluronic F127, or Pluronic F127 plus vitamin C (antioxidant sol-gel). The rate of wound contraction, the levels of epidermal and dermal maturation, collagen synthesis, and apoptosis production in the wound tissue were determined. In vitro data showed that after 6 hours of air exposure, the order of the scavenging abilities for HOCl, H(2)O(2), and O(2) (-) was antioxidant sol-gel > antioxidant saline > Pluronic F127 = saline. After 7 and 14 days of wound injury, the antioxidant sol-gel improved wound healing significantly by accelerated epidermal and dermal maturation, an increase in collagen content, and a decrease in apoptosis formation. However, the wounds of all treatments healed mostly at 3 weeks. Vitamin C in Pluronic F127 hastened cutaneous wound healing by its antioxidant and antiapoptotic mechanisms through a good drug delivery system. This study showed that Pluronic F127 plus vitamin C could potentially be employed as a novel wound-healing enhancer.
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http://dx.doi.org/10.1155/2012/504693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420222PMC
December 2012
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