Purpose: Pioglitazone, an antihyperglycemic drug, is widely used in diabetes mellitus patients with insulin resistance. Although pioglitazone is known to have a potential link to bladder cancer (BC), there have been contradictory results. This present study is designed to understand the regulatory mechanisms that drive the effects of pioglitazone on the bladder epithelial cells. Methods: Labeled liquid chromatography-tandem mass spectrometry-based proteomics profiling characterized the global proteomes of normal human bladder epithelial cells treated with or without pioglitazone. Results: This approach detected approximately 5,769 proteins in total. Of those 5,769 proteins, 124 were identified as being differentially expressed due to pioglitazone treatment. Further analysis identified 95 upregulated and 29 downregulated proteins (absolute log2 fold change >0.58 and P-value<0.05). The following functional gene enrichment analysis suggested that pioglitazone may be altering a few select biological processes, such as gene/chromatin silencing, by downregulating BMI1 (B lymphoma Mo-MLV insertion region 1 homolog), a polycomb complex protein. Further cell-based assays showed that cell adhesion molecules, epithelial-mesenchymal transition markers, and major signaling pathways were significantly downregulated by pioglitazone treatment. Conclusions These experimental results revealed the proteomic and biological alterations that occur in normal bladder cells in response to pioglitazone. These findings provided a landscape how bladder proteome is influenced by pioglitazone, which suggests the potential adverse effects of diabetes drugs and their links to bladder dysfunctions.

The advances in mass spectrometry-based proteomics technologies have enabled the generation of global proteome data from tissue or body fluid samples collected from a broad spectrum of human diseases. Comparative proteomic analysis of global proteome data identifies and prioritizes the proteins showing altered abundances, called differentially expressed proteins (DEPs), in disease samples, compared to control samples. Protein biomarker candidates that can serve as indicators of disease states are then selected as key molecules among these proteins. Recently, it has been addressed that cellular pathways can provide better indications of disease states than individual molecules and also network analysis of the DEPs enables effective identification of cellular pathways altered in disease conditions and key molecules representing the altered cellular pathways. Accordingly, a number of network-based approaches to identify disease-related pathways and representative molecules of such pathways have been developed. In this review, we summarize analytical platforms for network-based protein biomarker discovery and key components in the platforms.
Body Fluids ; Humans ; Proteome ; Proteomics ; Biomarkers

OBJECTIVE: Opioid analgesics, for postoperative pain management, are an indispensable group of medication; however, they also have a variety of adverse drug reactions (ADR). Multimodal methods, combining non-opioid analgesics with opioid analgesics, have been investigated to increase the effects of analgesics and reduce ADR with opioid-sparing effects. The purpose of this study was to compare the effects of patient-controlled analgesia (PCA) with fentanyl alone, and PCA with fentanyl and intravenous (i.v.) propacetamol to determine the effects of pain control, cumulative opioid usage, and opioid ADR. METHODS: The subjects were patients who underwent total knee arthroplasty at the Seoul Veterans hospital from January 1, 2015 to December 31, 2016. The study period was from postoperative day 0 (POD0) to day 3 (POD3), and the retrospective study was conducted using electronic medical records. RESULTS: Pain severity was significantly low at POD1 (p = 0.017), POD2 (p = 0.003), and POD3 (p = 0.002) in the multimodal group. The fentanyl only group frequently reported both moderate and severe pain at a statistically significant level. This was consistent with the analysis of the pro re nata (PRN) intramuscular analgesia usage at the time of numerical rating scale (NRS) 4 and above. The opioid-sparing effect confirmed that the average opioid dose equivalent to i.v. morphine dose was 9.4 mg more than that used for the multimodal group in the fentanyl only group. The ADRs and length of stay between the two groups were not statistically different. CONCLUSION: The results of this study suggest that the combination therapy of fentanyl and i.v. propacetamol is superior to fentanyl monotherapy.

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare and aggressive tumor that is genetically characterized by chromosomal rearrangement of the NUT gene. NMC predominantly involves the midline structures of the body and the sinonasal tract is considered a preferential site. While the optimal management of NMC is unclear, more than 80% of patients will die within one year of their diagnosis despite intensive treatment. We report two cases of NMC of the sinonasal tract. Histopathologic results of the punch biopsy showed undifferentiated and poorly differentiated carcinoma. NUT immunohistochemical staining results were positive. Multimodal treatments including surgery, radiotherapy, and chemotherapy were performed. We also present a literature review to compare with the present cases. In our cases, we emphasize the importance of the early diagnosis and intensive treatment of NMC.
Biopsy ; Combined Modality Therapy ; Diagnosis ; Drug Therapy ; Early Diagnosis ; Humans ; Nuclear Proteins* ; Nuts ; Radiotherapy ; Testis*

Hereditary hemorrhagic telangiectasia (HHT) is a hereditary, autosomal dominant, vascular dysplasia characterized by mucocutaneous telangiectasia, epistaxis, gastrointestinal bleeding, and iron deficiency anemia. Epistaxis in HHT is a recurrent and debilitating symptom, which is difficult to manage. Many methods have been tried with little success. Bevacizumab (Avastin®), a VEGF inhibitor, has been recently tried intranasally or systemically to control the recurrent epistaxis. We report three patients with HHT who were treated with intranasal bevacizumab application together with cauterization. In all three patients, recurrent epistaxis decreased considerably with improvement in quality of life. Here we describe the application methods, treatment results, and complications with literature review. We believe that this is the first report of treating epistaxis in HHT with intranasal application of bevacizumab in South Korea.
Anemia, Iron-Deficiency ; Bevacizumab* ; Cautery ; Epistaxis ; Hemorrhage ; Humans ; Korea ; Quality of Life ; Telangiectasia, Hereditary Hemorrhagic* ; Telangiectasis ; Vascular Endothelial Growth Factor A

Extended endotracheal intubation in infancy causes various complications. Upper airway disruption is very rare but reversible cause of respiratory insufficiency. Tracheostomy may not be avoidable in severe upper respiratory tract lesions especially in large subglottic cysts and severe subglottic stenosis; however, avoiding it is a priority when possible. A 7-month-old child who had a history of newborn respiratory distress syndrome and extended endotracheal intubation developed respiratory symptoms including stridor. A subglottic cyst was found by bronchoscopy and surginally removed with the tubeless anesthesia technique without tracheostomy. This method was successful even on infants. We report this case with a review of literature.

Background and Objectives: Parotid cancer is a rare malignancy tumor, constituting about 3% of head and neck cancers. Treatment of parotid carcinoma is challenging because of its rarity and unpredictable clinical course. Therefore, it is important to evaluate risk factors associated with prognosis and to predict adverse outcomes. In this article, we aimed to analyze risk factors associated with recurrence free survival in our 10-year single center retrospective study.Subjects and Method Retrospective medical chart review was performed for patients with parotid gland cancer who underwent parotidectomy with or without adjuvant treatment in our institute 2011 to 2020. Patient demographics, histopathologic results, operative method, treatment outcome were assessed. Results: A total of 8 patients (15%) experienced recurrence. Old age and low body mass index was associated with recurrence. Univariate analysis also revealed that high clinical stage, tumor involvement in deep lobe and facial nerve, postoperative radiotherapy or concurrent chemo radiotherapy, positive resection margin, and high histologic grade were statistically significant with recurrence. Multivariate analysis concluded that facial nerve involvement with tumor was associated with higher incidence of recurrence. Deep lobe and facial nerve involvement, postoperative radiotherapy or concurrent chemo radiotherapy, positive resection margin, clinical stage, and histologic grade were statistically significant factors associated with recurrence free survival. Conclusion Our 10-year single institute study will be helpful for predicting adverse outcomes in parotid cancer patients.

In Parkinson’s disease (PD) research, human neuroblastoma and immortalized neural cell lines have been widely used as in vitro models. The advancement in the field of reprogramming technology has provided tools for generating patient-specific induced pluripotent stem cells (hiPSCs) as well as human induced neuronal progenitor cells (hiNPCs). These cells have revolutionized the field of disease modeling, especially in neural diseases. Although the direct reprogramming to hiNPCs has several advantages over differentiation after hiPSC reprogramming, such as the time required and the simple procedure, relatively few studies have utilized hiNPCs. Here, we optimized the protocol for hiNPC reprogramming using pluripotency factors and Sendai virus. In addition, we generated hiNPCs of two healthy donors, a sporadic PD patient, and a familial patient with the LRRK2 G2019S mutation (L2GS). The four hiNPC cell lines are highly proliferative, expressed NPC markers, maintained the normal karyotype, and have the differentiation potential of dopaminergic neurons. Importantly, the patient hiNPCs show different apoptotic marker expression. Thus, these hiNPCs, in addition to hiPSCs, are a favorable option to study PD pathology.
Cell Line ; Dopaminergic Neurons ; Fibroblasts ; Humans ; In Vitro Techniques ; Induced Pluripotent Stem Cells ; Karyotype ; Neuroblastoma ; Neurons ; Pathology ; Sendai virus ; Stem Cells ; Tissue Donors

BACKGROUND: Long segmental tracheal repair is challenging in regenerative medicine due to low adhesion of stem cells to tracheal scaffolds. Optimal transplantation of stem cells for tracheal defects has not been established. We evaluated the role of hyaluronic acid (HA) coating of tracheal scaffolds in mesenchymal stem cell (MSC) adhesion and tracheal regeneration in a rabbit model. METHODS: A three-dimensionally printed tubular tracheal prosthesis was incubated with dopa-HA-fluorescein isothiocyanate in phosphate-buffered saline for 2 days. MSCs were incubated with an HA-coated scaffold, and their adhesion was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. HA coated scaffolds with or without MSC seeding were transplanted at the circumferential tracheal defect in rabbits, and survival, rigid bronchoscopy, radiologic findings, and histologic findings were compared between the two groups. RESULTS: HA-coated scaffolds showed better MSC adhesion than non-coated scaffolds. The HA-coated scaffolds with MSC group showed a wider airway and greater mucosal regeneration compared to the HA-coated scaffolds without MSC group. CONCLUSION HA coating of scaffolds can promote MSC adhesion and tracheal regeneration.

BACKGROUND: Long segmental tracheal repair is challenging in regenerative medicine due to low adhesion of stem cells to tracheal scaffolds. Optimal transplantation of stem cells for tracheal defects has not been established. We evaluated the role of hyaluronic acid (HA) coating of tracheal scaffolds in mesenchymal stem cell (MSC) adhesion and tracheal regeneration in a rabbit model. METHODS: A three-dimensionally printed tubular tracheal prosthesis was incubated with dopa-HA-fluorescein isothiocyanate in phosphate-buffered saline for 2 days. MSCs were incubated with an HA-coated scaffold, and their adhesion was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. HA coated scaffolds with or without MSC seeding were transplanted at the circumferential tracheal defect in rabbits, and survival, rigid bronchoscopy, radiologic findings, and histologic findings were compared between the two groups. RESULTS: HA-coated scaffolds showed better MSC adhesion than non-coated scaffolds. The HA-coated scaffolds with MSC group showed a wider airway and greater mucosal regeneration compared to the HA-coated scaffolds without MSC group. CONCLUSION HA coating of scaffolds can promote MSC adhesion and tracheal regeneration.