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1.
Rhinology ; 59(6): 528-537, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34636368

ABSTRACT

BACKGROUND: Urban particulate matter (UPM) in ambient air is implicated in a variety of human health issues worldwide, however, few studies exist on the effect of UPM on the olfactory system. This study aimed to identify the factors affecting the destruction of the olfactory system in a mouse model following UPM exposure. METHODS: Mice were divided into: control and four UPM-exposed groups (200 µg UPM at 1 and 2 weeks, and 400 µg UPM at 1 and 2 weeks [standard reference material 1649b; average particle diameter 10.5 µm]). The olfactory neuroepithelium was harvested for histologic examination, gene ontology, quantitative real-time polymerase chain reaction, and western blotting. RESULTS: Compared to the control group, olfactory marker protein, Olfr1507, ADCY3, and GNAL mRNA levels were lower, and S-100, CNPase, NGFRAP1, BDNF, and TACR3 mRNA levels were higher in the olfactory neuroepithelium of the UPM groups. Moderately positive correlation was present between the 1- and 2-week groups. After analyzing the 200 and 400 UPM groups separately, the strength of the association between the 200 UPM 1- and 2-week groups was moderately positive. No differences was present in the neuroepithelial inflammatory marker levels between the UPM and control groups. CONCLUSIONS: UPM could have cytotoxic effects on the olfactory epithelium. The exposure time and particular concentration of UPM exposure could affect the degree of destruction of the olfactory neuroepithelium. The olfactory regeneration mechanism could be related to the neurotrophic factors, olfactory ensheathing cell stimulation, and trigeminal nerve support.


Subject(s)
Particulate Matter , Smell , Animals , Mice , Olfactory Mucosa , Particulate Matter/toxicity , RNA, Messenger
2.
Eur Rev Med Pharmacol Sci ; 25(9): 3519-3529, 2021 05.
Article in English | MEDLINE | ID: mdl-34002826

ABSTRACT

OBJECTIVE: We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS). MATERIALS AND METHODS: Two investigators independently searched PubMed and EMBASE, and 191 cases were included in this study. Information regarding demographics, triggering factors, brain imaging findings, treatment modalities, recurrence, and clinical outcome was collected. RESULTS: The mean age of the patients was 39.9 years, and 155 (81.2%) were female. The most common triggering factor for RCVS was an exposure to vasoactive substances (41.4%), followed by pregnancy/postpartum (20.9%), and sexual intercourse (10.5%). Multifocal stenosis (84.0%) and beading shape (82.4%) were the leading abnormal findings on angiography, while cerebral ischemic lesions (47.6%) and cerebral hemorrhage (mainly subarachnoid hemorrhage) (35.1%) were the main findings on brain computed tomography (CT)/magnetic resonance imaging (MRI). Calcium channel blockers (nimodipine/verapamil) were the most commonly used medications (44.5%) in the treatment of RCVS. Multivariate analysis identified that RCVS was precipitated by trauma/surgery/procedure (hazard ratio (HR): 3.29, 95% confidence interval (CI) (1.21-8.88), p=0.019), and presence of aphasia/neglect/apraxia during the acute phase of the disease (HR: 3.83, 95% CI (1.33-11.05), p=0.013) were found to be the two independent risk factors for residual neurological deficit after RCVS. CONCLUSIONS: In our systematic review, vasoactive substances were the most frequent triggers for RCVS, which was most commonly accompanied by angiographic findings of multifocal stenotic lesions. Patients with RCVS precipitated by trauma or surgical procedures and those with focal cortical deficits had a higher risk of residual neurological deficits, and these patients should closely be monitored.


Subject(s)
Cerebrovascular Disorders/diagnostic imaging , Headache Disorders, Primary/diagnostic imaging , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Humans , Vasoconstriction
3.
Diabetes Metab ; 45(5): 453-457, 2019 10.
Article in English | MEDLINE | ID: mdl-30639566

ABSTRACT

AIM: This study investigated the clinical characteristics of diabetic ketoacidosis (DKA) and compared the DKA characteristics between patients treated with and without SGLT2 inhibitors. METHODS: Data were collected from patients aged ≥ 18 years admitted for DKA at nine centres in Korea between September 2014 and April 2017. The electronic medical records of these subjects were retrospectively reviewed. Based on their history of medications taken before admission, subjects were classified as either users or non-users of SGLT2 inhibitors and their clinical characteristics of DKA were compared. RESULTS: During the study, the main subtype of DKA episodes (n = 523) was identified as type 2 diabetes (51%). Average hospitalization duration was 11 days, and average intensive care unit (ICU) time was 2.5 days. The in-hospital mortality rate was 3%, but no users of SGLT2 inhibitors died during DKA treatment. In patients taking SGLT2 inhibitors (n = 15), DKA manifested at 124 days, on average, after starting the inhibitors (range: 7-380 days). Also, SGLT2 inhibitors users had significantly lower plasma glucose levels (413 mg/dL) compared with non-users (554 mg/dL), and longer ICU stays (4 vs. 2 days; P = 0.019). CONCLUSION: In this report of recent data on the clinical features of DKA in Korea, patients using SGLT2 inhibitors needed longer treatment in ICUs compared with non-users and had lower levels of blood glucose, whereas DKA associated with SGLT2 inhibitors was rare.


Subject(s)
Blood Glucose , Diabetes Mellitus/drug therapy , Diabetic Ketoacidosis/diagnosis , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Adult , Diabetes Mellitus/blood , Diabetes Mellitus/mortality , Diabetic Ketoacidosis/blood , Diabetic Ketoacidosis/mortality , Female , Hospital Mortality , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle Aged , Retrospective Studies , Treatment Outcome
5.
Nat Commun ; 7: 11116, 2016 Apr 06.
Article in English | MEDLINE | ID: mdl-27050161

ABSTRACT

A superconducting transition temperature (Tc) as high as 100 K was recently discovered in one monolayer FeSe grown on SrTiO3. The discovery ignited efforts to identify the mechanism for the markedly enhanced Tc from its bulk value of 8 K. There are two main views about the origin of the Tc enhancement: interfacial effects and/or excess electrons with strong electron correlation. Here, we report the observation of superconductivity below 20 K in surface electron-doped bulk FeSe. The doped surface layer possesses all the key spectroscopic aspects of the monolayer FeSe on SrTiO3. Without interfacial effects, the surface layer state has a moderate Tc of 20 K with a smaller gap opening of 4.2 meV. Our results show that excess electrons with strong correlation cannot induce the maximum Tc, which in turn reveals the need for interfacial effects to achieve the highest Tc in one monolayer FeSe on SrTiO3.

6.
Oncogene ; 35(27): 3503-13, 2016 07 07.
Article in English | MEDLINE | ID: mdl-26500057

ABSTRACT

The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.


Subject(s)
Cell Transformation, Neoplastic/genetics , Forkhead Box Protein M1/genetics , Liver/metabolism , Peroxiredoxins/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Animals , Blotting, Western , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cells, Cultured , Female , Forkhead Box Protein M1/metabolism , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice , Mice, Knockout , Mice, Nude , Mice, Transgenic , NIH 3T3 Cells , Peptides/pharmacology , Peroxiredoxins/metabolism , Proto-Oncogene Proteins p21(ras)/metabolism , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Signal Transduction/genetics , Transplantation, Heterologous
7.
Clin Genet ; 90(2): 177-81, 2016 08.
Article in English | MEDLINE | ID: mdl-26662885

ABSTRACT

Large insertions and deletions (indels), including copy number variations (CNVs), are commonly seen in many diseases. Standard approaches for indel detection rely on well-established methods such as qPCR or short tandem repeat (STR) markers. Recently, a number of tools for CNV detection based on next-generation sequencing (NGS) data have also been developed; however, use of these methods is limited. Here, we used whole-exome sequencing (WES) in patients previously diagnosed with CMT1A or HNPP using STR markers to evaluate the ability of WES to improve the clinical diagnosis. Patients were evaluated utilizing three CNV detection tools including CONIFER, ExomeCNV and CEQer, and array comparative genomic hybridization (aCGH). We identified a breakpoint region at 17p11.2-p12 in patients with CMT1A and HNPP. CNV detection levels were similar in both 6 Gb (mean read depth = 80×) and 17 Gb (mean read depth = 190×) data. Taken together, these data suggest that 6 Gb WES data are sufficient to reveal the genetic causes of various diseases and can be used to estimate single mutations, indels, and CNVs simultaneously. Furthermore, our data strongly indicate that CNV detection by NGS is a rapid and cost-effective method for clinical diagnosis of genetically heterogeneous disorders such as CMT neuropathy.


Subject(s)
Arthrogryposis/genetics , Charcot-Marie-Tooth Disease/genetics , Chromosomes, Human, Pair 17/chemistry , DNA Copy Number Variations , Exome , Hereditary Sensory and Motor Neuropathy/genetics , INDEL Mutation , Arthrogryposis/diagnosis , Arthrogryposis/pathology , Charcot-Marie-Tooth Disease/diagnosis , Charcot-Marie-Tooth Disease/pathology , Chromosome Breakpoints , Comparative Genomic Hybridization , Genome-Wide Association Study , Hereditary Sensory and Motor Neuropathy/diagnosis , Hereditary Sensory and Motor Neuropathy/pathology , High-Throughput Nucleotide Sequencing , Humans , Microsatellite Repeats , Software
8.
Rhinology ; 53(4): 353-8, 2015 12.
Article in English | MEDLINE | ID: mdl-26275466

ABSTRACT

BACKGROUND: Berberine (Ber), used widely as an antibacterial, antifungal, and anti-inflammatory drug, has long been used as a gastrointestinal remedy in Chinese traditional medicine. Recent reports have suggested that Ber suppresses Th17 responses that was mediated by direct actions on T cells and thymic stromal lymphopoietin production in primary mast cells. It has been suggested that Ber may be useful in treating allergic response. The purpose of this study was to assess the effects of Ber treatment on allergic inflammation in an allergic rhinitis mouse model and to examine the underlying mechanism(s). METHODS: BALB/c mice were divided into control, Derf with no treated (Derf), Ber treated, and Ber with anti-C25 monoclonal antibody treated (Ber + anti-CD25) groups. All mice, with the exception of the control group, were sensitized with an intraperitoneal i.p. injection of Dermatophagoides farinae (Derf). Mice in the Ber and Ber + anti-CD25 group were treated intranasally with 10 #181;g/mL. Then, 1 week after sensitization, all mice were challenged intranasally with 20 #181;g Derf for 5 consecutive days. Mice in the anti-CD25 group were treated intraperitoneally with 250 #181;g anti-CD25 monoclonal antibody 1 day before the first intra-nasal challenge with Derf. Allergic symptom scores, eosinophil counts, and serum Derf-specific IgE levels were measured. T-bet, GATA-3, interferon-g (IFN-γ), interleukin (IL)-10, IL-13, and Foxp3 expression was examined by real-time polymerase chain reaction and Western blotting. CD4⁺ CD25⁺ Foxp3⁺ T cells were assessed by flow cytometry. RESULTS: Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, T-bet mRNA levels, and tissue eosinophil counts were decreased in the Ber versus the Derf group. In the Ber + anti-CD25 group, serum IL-10 levels were decreased versus the control, Derf, and Ber groups. In the Ber + anti-CD25 mAb groups, Foxp3 mRNA levels were decreased versus the control group. In the Ber group, Foxp3 mRNA levels were increased versus the control group. In the Ber group, the percentage of CD4⁺ CD25⁺ Foxp3⁺ T cells was increased versus the Derf group. The percentage of CD4⁺ CD25⁺ Foxp3+ T cells was increased in the Ber versus the Derf groups. CONCLUSIONS: In our study, Ber reduced allergic inflammation significantly. Moreover, our findings suggest that the mechanism of action of Ber may be via CD4⁺ CD25⁺ Foxp3⁺ Treg cells, possibly through not only by increasing their numbers but also altering their function.


Subject(s)
Berberine/therapeutic use , Dermatophagoides farinae/immunology , Phytotherapy , Rhinitis, Allergic/drug therapy , Animals , Berberine/pharmacology , Blotting, Western , Cytokines/metabolism , Disease Models, Animal , Drug Evaluation, Preclinical , Eosinophils , Female , Flow Cytometry , Immunoglobulin E/blood , Mice, Inbred BALB C , Mucous Membrane/immunology , Mucous Membrane/metabolism , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Random Allocation , Real-Time Polymerase Chain Reaction , Rhinitis, Allergic/blood , Rhinitis, Allergic/immunology
9.
Indian J Pharm Sci ; 77(5): 645-50, 2015.
Article in English | MEDLINE | ID: mdl-26798185

ABSTRACT

Agastachis Herba is one of the well-known medicinal herbs in Korean traditional medicine. This study was taken up to examine the beneficial effects of Agastachis Herba on a mice model of asthma. BALB/c mice were sensitized and challenged with ovalbumin to produce a murine model of asthma. Methanol extracts of Agastachis Herba were orally administered to the ovalbumin-induced asthmatic mice. The effects of methanol extract of Agastachis Herba on airway hyper responsiveness, immune cell distributions in bronchoalveolar lavage fluid, ovalbumin-specific immunoglobulin E in serum, and histopathological changes were evaluated. Mice treated with the methanol extract of Agastachis Herba showed reduction of airway hyper responsiveness as well as inhibited immune cell infiltration in bronchoalveolar region. Also ovalbumin-specific immunoglobulin E levels in bronchoalveolar lavage fluid significantly decreased in extract treated mice. Histopathological findings showed significant beneficial changes in inflammatory cell infiltration.

10.
Transplant Proc ; 46(4): 1139-44, 2014 May.
Article in English | MEDLINE | ID: mdl-24815147

ABSTRACT

Autologous chondrocyte transplantation involves isolating chondrocytes from a patient's cartilage tissue. Storage conditions such as storage time and temperature are important for the quality of the isolated cells. However, few studies have focused on variables for optimum tissue preservation, and there is neither an established method for storing cartilage nor reliable reports on how different conditions affect the isolated chondrocytes. Therefore, in the present study, we stored cartilage in various preservation solutions, under different temperatures, and for varying durations and determined their effects on the characteristics and viability of isolated chondrocytes. We assessed chondrocyte viability with the use of a cell proliferation assay and determined their chondrogenic potential with the use of reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and glycosaminoglycan assays. Our results demonstrated that cartilage tissue stored in a preservation medium composed of dimethyl sulfoxide, fetal bovine serum, and Dulbecco Modified Eagle Medium at a ratio of 1:2:7 (v/v) or stored with a commercially available preservation solution generated greater numbers of chondrocytes when the storage temperature was -80°C than when it was 4°C. The viability of isolated cells decreased with time at 4°C, whereas these values remained constant for tissues stored at -80°C. Our data suggest that an optimal method for preserving cartilage tissue is required to ensure the quality of cells used for transplantation.


Subject(s)
Cartilage, Articular/drug effects , Chondrocytes/drug effects , Cold Temperature , Cryopreservation/methods , Organ Preservation Solutions/pharmacology , Animals , Autografts , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Cartilage, Articular/surgery , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Chondrocytes/metabolism , Chondrocytes/pathology , Chondrocytes/transplantation , Chondrogenesis/drug effects , Chondrogenesis/genetics , Culture Media/pharmacology , Dimethyl Sulfoxide/pharmacology , Gene Expression Regulation , Glycosaminoglycans/metabolism , Male , RNA, Messenger/metabolism , Rabbits , Serum , Time Factors
11.
Transplant Proc ; 46(4): 1145-9, 2014 May.
Article in English | MEDLINE | ID: mdl-24815148

ABSTRACT

Autologous chondrocyte transplantation (ACT) is an effective and safe therapy for repairing articular cartilage defects and requires cell preservation and subculture before transplantation. We compared the effects of cryopreservation and passaging on cell viability, proliferation, and maintenance of the function of chondrocytes and synovium-derived mesenchymal stem cells (MSCs) used as sources for ACT. These cells were isolated from the knee joints of rabbits and were cultured, passaged serially, and divided into 2 groups that were either cryopreserved or not. The morphology, viability, gene expression, and differentiation potential of the 2 groups were compared. Maintenance of the potential to undergo chondrogenic differentiation was determined with the use of a 3-dimensional culture method. Passaging and cryopreservation significantly affected the ability of chondrocytes to maintain their morphology, express chondrogenic genes, and differentiate. In contrast, synovium-derived cells were not affected by passaging and cryopreservation. Our results may serve as the foundation for the application of passaged and cryopreserved chondrocyte or other source cells of MSCs in ACT.


Subject(s)
Cell Proliferation , Chondrocytes/pathology , Cryopreservation , Mesenchymal Stem Cells/pathology , Synovial Membrane/pathology , Animals , Autografts , Cell Differentiation/genetics , Cell Shape , Cell Survival , Cells, Cultured , Chondrocytes/metabolism , Chondrocytes/transplantation , Chondrogenesis/genetics , Gene Expression Regulation , Glycosaminoglycans/metabolism , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , RNA, Messenger/metabolism , Rabbits , Synovial Membrane/metabolism , Synovial Membrane/transplantation
12.
Transplant Proc ; 46(4): 1156-60, 2014 May.
Article in English | MEDLINE | ID: mdl-24815150

ABSTRACT

Pancreatic islets have been the focus of recent studies exploring the pathologic mechanisms of diabetes mellitus as well as more effective and radical treatments for this disease. Islet transplantation is a promising therapeutic strategy; however, isolation of pancreatic islets for this purpose has been challenging, because the technique is time consuming and technically difficult, and tissue handling can be variable. Pseudo-islets can be used as an alternative to naïve islets, but require cellular sources or artificial materials. In this study, pancreas-derived cells were used to generate pseudo-islets. Because the pancreas is composed of a variety of cell types, namely α cells, ß cells, δ cells, and other pancreatic cells that perform different functions, we used 3 different cell lines-NIT-1 (a ß-cell line), α TC1 clone 6 (an α-cell line), and TGP52 (a pancreatic epithelial-like cell line)-which we cocultured in nonadhesive culture plates to produce hybrid cellular spheroids. These pseudo-islets had an oval shape and were morphologically similar to naïve islets; additionally, they expressed and secreted the pancreatic hormones insulin, glucagon, and somatostatin, as confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. The results demonstrate that pseudo-islets that mimic naïve islets can be successfully generated by a coculture method. These artificial islets can potentially be used for in vitro tests related to diabetes mellitus, specifically, in drug discovery or for investigating pathology. Moreover, they can be useful for examining basic questions pertaining to cell-cell interactions and tissue development.


Subject(s)
Bioartificial Organs , Islets of Langerhans/cytology , Tissue Engineering/methods , Animals , Cell Communication , Cell Line, Tumor , Cell Shape , Coculture Techniques , Gene Expression Regulation , Glucagon/genetics , Glucagon/metabolism , Insulin/genetics , Insulin/metabolism , Insulin Secretion , Islets of Langerhans/metabolism , Islets of Langerhans Transplantation , Mice , RNA, Messenger/metabolism , Somatostatin/genetics , Somatostatin/metabolism , Spheroids, Cellular , Time Factors
13.
Transplant Proc ; 46(4): 1247-50, 2014 May.
Article in English | MEDLINE | ID: mdl-24815172

ABSTRACT

Autologous chondrocyte transplantation (ACT) has been established to contribute cartilage regeneration over the past years; however, many obstacles need to be overcome. Recently, newer ACT technique involves cotransplantation of chondrocytes and biomaterial. Although various proposed intelligent biomaterials exist, many of them remain insufficient and controversial. In this study, we aimed to examine the effects of natural extracellular matrix (ECM) to the proliferation rate and differentiation on the chondrocytes. We first derived a natural ECM sheet from 10-µm-thick frozen sections of porcine knee cartilages. We then cultured the chondrocytes derived from a rabbit's knee on a dish precoated with the natural ECM. Then we assessed differentiation and chondrogenic potential of the cells compared with those grown in untreated culture dishes. We characterized the gene expression of chondrogenic markers, such as collagen type II, SOX-9, and aggrecan, as well as the level of ECM protein with the use of reverse-transcription polymerase chain reaction analysis. The cells cultured with the ECM sheet showed highest chondrogenic potential and differentiation. Therefore, we can induce good chondrogenesis by with the use of a natural ECM sheet on the culture dish. The readily available and easy-to-handle thin ECM sheets create an environment that promotes efficient cartilage regeneration. Our data suggest that this natural ECM scaffold improved the chondrogenic differentiation of the cells in vitro by providing a favorable microenvironment.


Subject(s)
Cartilage/cytology , Cartilage/metabolism , Cellular Microenvironment , Chondrocytes/metabolism , Chondrogenesis , Extracellular Matrix/metabolism , Tissue Engineering/methods , Animals , Cartilage/transplantation , Cell Differentiation , Cell Proliferation , Cells, Cultured , Chondrocytes/transplantation , Chondrogenesis/genetics , Gene Expression Regulation , Genetic Markers , Male , Rabbits , Regeneration , Swine
14.
Cell Death Dis ; 4: e974, 2013 Dec 19.
Article in English | MEDLINE | ID: mdl-24357805

ABSTRACT

Cystatin SN (CST1) is one of the several salivary cystatins that form tight equimolar complexes with cysteine proteases, such as the cathepsins. High expression of CST1 is correlated with advanced pTNM stage in gastric cancer. However, the functional role of CST1 in tumorigenesis has not been elucidated. In this study, we showed that CST1 was highly expressed in colon tumor tissues, compared with nontumor regions. Increased cell proliferation and invasiveness were observed in HCT116 cell lines stably transfected with CST1 cDNA (HCT116-CST1) but not in CST3-transfected cells. We also demonstrated that CST1-overexpressing cell lines exhibited increased tumor growth as well as metastasis in a xenograft nude mouse model. Interestingly, CST1 interacted with cystatin C (CST3), a potent cathepsin B (CTSB) inhibitor, with a higher affinity than the interaction between CST3 and CTSB in the extracellular space of HCT116 cells. CTSB-mediated cellular invasiveness and proteolytic activities were strongly inhibited by CST3, but in the presence of CST1 CTSB activities recovered significantly. Furthermore, domain mapping of CST1 showed that the disulfide-bonded conformation, or conserved folding, of CST1 is important for its secretion and for the neutralization of CST3 activity. These results suggest that CST1 upregulation might be involved in colorectal tumorigenesis and acts by neutralizing the inhibition of CTSB proteolytic activity by CST3.


Subject(s)
Cathepsin B/metabolism , Cystatin C/metabolism , Salivary Cystatins/metabolism , Animals , Blotting, Western , Cathepsin B/genetics , Cell Line , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Cystatin C/genetics , HCT116 Cells , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Microscopy, Confocal , Reverse Transcriptase Polymerase Chain Reaction , Salivary Cystatins/genetics
15.
Transplant Proc ; 45(8): 3108-12, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24157045

ABSTRACT

BACKGROUND: Before cell or tissue transplantation, cells or tissues have to be maintained for a certain period in vitro using culture medium and methods. Most culture media contain substances such as pH indicators and buffers. It is not known whether some of these substances are safe for subsequent application in the transplantation of cells or tissues into the human body. We investigated culture media and methods with respect to the safety of the components in future transplantation applications. METHODS: A modified culture medium--medical fluid-based culture medium (FCM)--was designed by using various fluids and injectable drugs that are already currently permitted for use in clinical medicine. Medium components necessary for optimal cell growth were obtained from approved drugs. FCM was manufactured with adjusted final concentrations of the medium components similar to those in commercial Dulbecco's modified Eagle's medium (DMEM). In particular, 1029.40 mg/L amino acids, approximately 88.85 mg/L vitamins, 13,525.77 mg/L inorganic salts, and 4500 mg/L D-glucose comprise the high-glucose FCM. Next, human fat synovium-derived mesenchymal stem cells and rat H9c2 (2-1) cells were cultured under 2 conditions: (1) DMEM-high glucose (HG), an original commercial medium, and (2) optimized FCM-HG. We assessed the morphologies and proliferation rates of these cells. RESULTS: We observed that FCM-HG was able to induce the growth of FS-MSC and commercially available H9c2 cell. The morphologies and proliferation patterns of these cells cultured under FCM-HG showed no differences compared with cells grown in DMEM-HG. CONCLUSION: Our data suggest that FCM, which we developed for the first time according to the concept of drug repositioning, was a useful culture medium, especially in cultured cells intended for human cell transplantation.


Subject(s)
Cell Transplantation , Cells, Cultured , Culture Media , Humans
16.
Transplant Proc ; 45(8): 3113-7, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24157046

ABSTRACT

Investigators conducting diabetes-related research have focused on islet transplantation as a radical therapy for type 1 diabetes mellitus. Pancreatic islet isolation, an essential process, is a very demanding work because of the proteolytic enzymes, species, treatment time, and individual difference. Replacement of primary isolated pancreatic islets must be carried out continuously for various in vitro tests, making primary isolated islets a useful tool for cell transplantation research. Hence, we sought to develop pseudoislets from commercial pancreas-derived cell lines. In this study, we used RIN-5F and RIN-m cells, which secrete insulin, somatostatin, or glucagon. To manufacture hybrid cellular spheroids, the cells were cultured under hanging drop plate and nonadhesive plate methods. We observed that hybrid cellular pseudoislets exhibited an oval shape, with sizes ranging from 590 to 1200 µm. Their morphology was similar to naïve islets. Cell line pseudoislets secreted and expressed insulin, glucagon, and somatostatin, as confirmed by reverse transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry analyses. Thus, the current artificially manufactured biomimetic pseudoislets resembled pancreatic islets of the endocrine system, appearing as cellular aggregates that secreted insulin, glucagon, and somatostatin. Enhanced immunoisolation techniques may lead to the development of new islet sources for pancreatic transplantation through this pseudoislet strategy.


Subject(s)
Islets of Langerhans/metabolism , Spheroids, Cellular/metabolism , Animals , Cell Line , Fluorescent Antibody Technique , Fluorescent Dyes , Islets of Langerhans/cytology , Rats , Reverse Transcriptase Polymerase Chain Reaction
17.
Transplant Proc ; 45(8): 3118-21, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24157047

ABSTRACT

Mesenchymal stem cells (MSCs) are multipotent stromal elements that can differentiate into a variety of cell types. MSCs are good sources of therapeutic cells for degenerative diseases. For these reason, many researchers have focused on searching for other sources of MSCs. To obtain MSCs for clinical use requires surgery of the donor that therefore can induce donor morbidity, since the common sources at present are bone marrow and adipose tissues. In this study, we investigated the existence of MSCs in postoperative discarded tissues. Subacromial bursal tissues were obtained from the shoulders of 3 injured patients. The cells from the bursa tissues were isolated through treatment with collagenase. The isolated cells were then seeded and expanded by serial passaging under normal culture system. To evaluate MSC characteristics of the cells, their MSC markers were confirmed by mRNA and protein expression. Multipotent ability was assessed using differentiation media and immunohistochemistry. Cells from the bursa expressed MSCs markers-CD29, CD73, CD90, and PDGFRB (platelet-derived growth factor receptor-beta). Moreover, as to their multipotency, bursal cells differentiated into adipocytes (fat cells), osteocytes (bone cells), and chondrocytes (cartilage cells). In summary, we showed that MSCs could be generated from the subacromial bursa, which is medical waste after surgery.


Subject(s)
Mesenchymal Stem Cells/physiology , Shoulder/physiology , Cell Differentiation , Humans , Mesenchymal Stem Cells/cytology
19.
Skin Res Technol ; 19(1): e45-53, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22211382

ABSTRACT

BACKGROUND: Enlarged facial pores have been esthetic problems and have become a matter of cosmetic concern. Several factors are supposed to be related to the enlargement of facial pores, although scientific evaluations were not performed yet. OBJECTIVE: To assess the correlation between facial pores and possible relating factors such as age, gender, sebum secretion, skin elasticity, and the presence of acne, using objective bioengineering instruments. METHODS: Sixty volunteers, 30 males and 30 females, participated in this study. Various parameters of facial pores were assessed using the Robo Skin Analyzer. The facial sebum secretion and skin elasticity were measured using the Sebumeter and the Cutometer, respectively. These data were compared and correlated to examine the possible relationship between facial pores and age, sebum secretion and skin elasticity, according to gender and the presence of acne. RESULTS: Male gender and the existence of acne were correlated with higher number of facial pores. Sebum secretion levels showed positive correlation with facial pores. The R7 parameter of skin elasticity was negatively correlated with facial pores, suggesting increased facial pores with decreased skin elasticity. However, the age and the severity of acne did not show a definite relationship with facial pores. CONCLUSION: Male, increased sebum and decreased skin elasticity were mostly correlated with facial pore development. Further studies on population with various demographic profiles and more severe acne may be helpful to elucidate the potential effect of aging and acne severity on facial pores.


Subject(s)
Acne Vulgaris/metabolism , Acne Vulgaris/pathology , Face , Sebum/metabolism , Sex Characteristics , Skin/pathology , Adult , Age Factors , Bioengineering , Elasticity , Elasticity Imaging Techniques , Female , Humans , Male , Sebum/cytology , Severity of Illness Index , Skin/metabolism , Skin Aging/pathology , Skin Aging/physiology , Young Adult
20.
Poult Sci ; 91(9): 2370-5, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22912475

ABSTRACT

Prevalence and antimicrobial resistance profiles of Salmonella serotypes isolated from 7 chicken meat brands produced by different integrated broiler operations in Korea were determined. In total, 210 samples were collected from retail supermarkets in Seoul, South Korea, and analyzed for the presence of Salmonella. Of 210 chicken meat samples, overall Salmonella prevalence was 22.4%. Salmonella Enteritidis was the dominant serovar, with an isolation rate of 57.4% from the Salmonella-positive chickens, followed by Salmonella Montevideo. Salmonella isolates frequently were resistant to various antibiotics, including 100% to erythromycin, 87% to cephalothin, 85% to nalidixic acid, and 70% to streptomycin. Of the 47 isolates, 41 (87.2%) isolates were resistant to 3 or more antibiotics. Moreover, the Salmonella profiles of each chicken meat brand were different by broiler operation. Brand A showed the highest prevalence of Salmonella (18 isolates, 60%), whereas brand G showed the lowest prevalence (one isolate, 3.3%). Eight among the 18 isolates of brand A were resistant to 11 antibiotics, whereas 5 of the 6 brand C isolates were resistant to only 2 antibiotics. This study demonstrates that a high proportion of chicken meat in Korea is contaminated with Salmonella and the prevalence and antimicrobial resistance patterns of Salmonella of chicken meat differ significantly according to the integrated broiler operation.


Subject(s)
Animal Husbandry/methods , Anti-Bacterial Agents/pharmacology , Meat/microbiology , Salmonella/classification , Salmonella/drug effects , Animals , Chickens/microbiology , Drug Resistance, Bacterial , Prevalence , Republic of Korea , Serotyping
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