The Effect of Mesenchymal Stem Cells on Dry Eye in Sjogren Syndrome Mouse Model.

Sjögren's syndrome (SS) is a systemic autoimmune disease delineated by chronic lymphocytic infiltrates into the lacrimal or salivary glands, leading to severe dry eye and dry mouth. Mesenchymal stem cells have been shown to be effective in treating numerous autoimmune diseases. This study aimed to illustrate the effects of mesenchymal stem cells on the attenuation of dry eyes (DE) through the inhibition of autophagy markers in a SS mouse model. NOD/ShiLtJ female mice with developed DE were treated with either subconjunctival or lacrimal gland injections of hMSCs (Catholic MASTER Cells). After maintenance for 14 days, clinical DE markers such as tear secretion and corneal staining were observed, as well as goblet cell counts in the conjunctiva, infiltration of inflammatory foci, B and T cells, and autophagy markers in the lacrimal glands. Proinflammatory cytokine expressions of the cornea and conjunctiva, as well as the lacrimal glands, were examined. Clinical markers, such as tear secretion and corneal stain scores, goblet cell counts in the conjunctiva, and foci infiltrations in the lacrimal glands were attenuated in mice treated with subconjunctival or lacrimal gland injections of hMSCs compared to the PBS-treated control group. B cell marker B220 decreased in the lacrimal glands of hMSCs-treated mice, as well as reduced proinflammatory cytokine expressions in the lacrimal glands and cornea. Notably, expression of autophagy markers ATG5 and LC3B-II, as well as HIF-1α and mTOR which play roles in the pathways of autophagy modulation, were shown to be attenuated in the lacrimal glands of hMSCs-treated mice compared to the PBS-treated control mice. Treatment with hMSCs by lacrimal gland or subconjunctival injection demonstrated the alleviation of DE through the repression of autophagy markers, suggesting the therapeutic potentials of hMSCs in a SS mouse model.

Diquafosol ophthalmic solution enhances mucin expression via ERK activation in human conjunctival epithelial cells with hyperosmotic stress.

Purpose: To evaluate the effect of diquafosol tetrasodium on the expression of secretory and membrane-associated mucins in multi-layered cultures of primary human conjunctival epithelial cells (HCEC) using intracellular extracellular signal regulated kinase (ERK) signaling. Methods: HCECs were treated with hyperosmotic stress (400 mOsm/l) for 24 h after air-liquid interface cell culture followed by treatment with diquafosol. HCECs were stimulated for 1 h with or without PD98059, an ERK inhibitor, then treated with diquafosol for 6 h and 24 h. Mucin 1 (MUC1), mucin 16 (MUC16), and MUC5AC mRNA and protein expression levels were analyzed, and cell viability was detected using an MTT assay. Western blot analysis was used to examine p44/42 MAPK (Erk1/2) and phosphorylated p44/42 MAPK (Erk1/2) expression. Results: Hyperosmotic stressed HCECs demonstrated increased MUC5AC secretion and gene expression when treated with diquafosol. MUC1 mRNA levels increased significantly at 24 h (p<0.01), and expression of MUC16 mRNA levels increased at 6 h and were maintained until 24 h (p<0.05).There was no significant difference in cell viability compared to the control group. Immunostaining results for MUC1, MUC16, and MUC5AC in diquafosol tetrasodium-treated HCECs at 24 h showed more positive cells than in the control group. Phosphorylation of p44/42 MAPK (Erk1/2) signaling molecules significantly increased from 5 min to 60 min (p<0.05). The effects of diquafosol on mucin expressions in hyperosmotic stressed HCECs were significantly inhibited by PD98059, an ERK inhibitor, at 6 h and 24 h. Conclusions: ERK signaling may regulate the expression levels of MUC1, MUC16, and MUC5AC induced by diquafosol in hyperosmotic stressed HCECs.

Cholesterol Efflux and Collateral Circulation in Chronic Total Coronary Occlusion: Effect-Circ Study.

Background The mechanism through which high-density lipoprotein (HDL) induces cardioprotection is not completely understood. We evaluated the correlation between cholesterol efflux capacity (CEC), a functional parameter of HDL, and coronary collateral circulation (CCC). We additionally investigated whether A1BP (apoA1-binding protein) concentration correlates with CEC and CCC. Methods and Results In this case-control study, clinical and angiographic data were collected from 226 patients (mean age, 58 years; male, 72%) with chronic total coronary occlusion. CEC was assessed using a radioisotope and J774 cells, and human A1BP concentration was measured using enzyme-linked immunosorbent assay. Differences between the good and poor CCC groups were compared, and associations between CEC, A1BP, and other variables were evaluated. Predictors of CCC were identified by multivariable logistic regression analysis. The CEC was higher in the good than in the poor CCC group (22.0±4.6% versus 20.2±4.7%; P=0.009). In multivariable analyses including age, sex, HDL-cholesterol levels, age (odds ratio [OR], 0.96; P=0.003), and CEC (OR, 1.10; P=0.004) were identified as the independent predictors of good CCC. These relationships remained significant after additional adjustment for diabetes mellitus, acute coronary syndrome, and Gensini score. The A1BP levels were not significantly correlated with CCC (300 pg/mL and 283 pg/mL in the good CCC and poor CCC groups, respectively, P=0.25) or CEC. Conclusions The relationship between higher CEC and good CCC indicates that well-functioning HDL may contribute to CCC and may be cardioprotective; this suggests that a specific function of HDL can have biological and clinical consequences.

Evaluation of the Efficacy and Safety of A Novel 0.05% Cyclosporin A Topical Nanoemulsion in Primary Sjögren's Syndrome Dry Eye.

Purpose: To evaluate the efficacy and safety of a novel topical cyclosporin A 0.05% nanoemulsion in comparison with a conventional emulsion in primary Sjögren's syndrome dry eyes.Methods: Prospective, randomized, double-blinded study was conducted.Results: Corneal and conjunctival staining score was improved in both groups, with a faster change noted in the nanoemulsion group at 12 weeks (p < 0.05). Tear film break-up time was significantly improved in the nanoemulsion group at 12 weeks (p < 0.05), while ocular surface disease index score was improved in both groups without a difference at 12 weeks. Schirmer I value and goblet cell grade did not change in both groups. IL-6 and MMP-9 were significantly decreased in both groups at 12 weeks.Conclusions: Both nanoemulsion and conventional cyclosporin A improved ocular signs, symptoms, and conjunctival inflammation. However, the novel cyclosporin A nanoemulsion showed faster improvement of ocular surface staining scores than the conventional emulsion.

Novel Associations between Related Proteins and Cellular Effects of High-Density Lipoprotein.

BACKGROUND AND OBJECTIVES: Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL. METHODS: HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio. RESULTS: After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories. CONCLUSIONS: In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.

The Effect of Chloroquine on the Development of Dry Eye in Sjögren Syndrome Animal Model.

Purpose: Sjögren syndrome (SS) is an autoimmune disease characterized by the inflammatory destruction of salivary and lacrimal glands (LG). Chloroquine (CQ) was known as an immunomodulatory drug and in the inhibition of autophagy. The purpose of the study is to investigate the effect of CQ on the development of dry eye in NOD-LtJ mice. Methods: NOD-LtJ mice were observed, during which the occurrence of dry eye was confirmed by tear secretion, corneal staining, and the infiltration of foci into the LG from 13-week-old mice. Intraperitoneal (IP) administration of CQ was performed in 13-week-old mice for 4 weeks and maintained untreated for another 4 weeks. Additionally, CQ was injected IP in 19-week-old mice for 2 weeks from when the disease was fully developed. Results: Interestingly, the expression of autophagy marker ATG5 and LC3B-II was observed in the LG from week 5. When CQ had been administered for 4 weeks from week 13 and then maintained untreated for 4 weeks, tear secretion, corneal staining score, foci formation in the LG, conjunctival goblet cells and proinflammatory cytokine expressions were significantly better than untreated mice. The infiltration of immune cells and the expression of autophagy markers in LG were decreased in the CQ group. These indices improved significantly as well when the 19-week-old mice with severe clinical phenotypes had been treated with CQ for 2 weeks. Conclusions: This study demonstrated that autophagy was induced in the early stages of the SS model and that CQ treatment in the early stages could inhibit disease progression.

The improvement of right ventricular function after adenotonsillectomy in children with obstructive sleep apnea.

PURPOSE: Adenotonsillar hypertrophy (ATH) that causes upper airway obstruction might lead to chronic hypoxemic pulmonary vasoconstriction and right ventricular (RV) dysfunction. We aimed to evaluate whether adenotonsillectomy (T&A) in children suffering from obstructive sleep apnea (OSA) due to severe ATH could improve RV function. METHODS: Thirty-seven children (boy:girl=21:16; mean age, 9.52±2.20 years), who underwent T&A forsleep apnea due to ATH, were included. We analyzedthe mean pulmonary artery pressure (mPAP), the presence and the maximal velocity of tricuspid regurgitation (TR), the tricuspid annular plane systolic excursion (TAPSE), and the right ventricular myocardial performance index (RVMPI) with tissue Doppler echocardiography (TDE) by transthoracic echocardiography pre- and post-T&A. The follow-up period was 1.78±0.27 years. RESULTS: Only the RVMPI using TDE improved after T&A (42.18±2.03 vs. 40±1.86, P=0.001). The absolute value of TAPSE increased (21.45±0.90 mm vs. 22.30±1.10 mm, P=0.001) but there was no change in the z score of TAPSE pre- and post-T&A (1.19±0.34 vs. 1.24±0.30, P=0.194). The mPAP was within normal range in children with ATH, and there was no significant difference between pre- and post-T&A (19.6±3.40 vs. 18.7±2.68, P=0.052). There was no difference in the presence and the maximal velocity of TR (P=0.058). CONCLUSION: RVMPI using TDE could be an early parameter of RV function in children with OSA due to ATH.

Clinical manifestation of Campylobacter enteritis in children.

PURPOSE: Timely antibiotic therapy in selected cases of diarrhea associated with bacterial infections can reduce the duration and severity of illness and prevent complications. The availability of a predictive index before identification of causative bacteria would aid in the choice of a therapeutic agent. METHODS: The study included patients admitted to the pediatrics unit at Konyang University Hospital for acute inflammatory diarrhea from August 1, 2015 to July 31, 2016 who underwent multiplex polymerase chain reaction testing. Of 248 patients, 83 had positive results. The clinical symptoms and blood test results were examined in 61 patients with Campylobacter spp. (25 patients), Salmonella spp. (18 patients), and Clostridium perfringens (18 patients) infections. The mean age of the 61 patients (male:femal=31:30) was 84.0±54.8 months, and the mean hospital stay was 4.6±1.7 days. RESULTS: There were no statistical differences in sex, age, clinical symptoms, or signs. Patients with Campylobacter infection were significantly older (P=0.00). C-reactive protein (CRP) levels in patients with Campylobacter infection were higher than those in the other 2 groups, at 9.6±6.1 mg/dL. The results of receiver-operating characteristic curve analysis showed that the cutoff age was ≥103.5 months (sensitivity, 72%; specificity, 86%) and the CRP cutoff level was ≥4.55 mg/dL (sensitivity, 80%; specificity, 69%). CONCLUSION: Age (≥103.5 months) and higher CRP level (≥4.55 mg/dL) were good predictors of Campylobacter enterocolitis. If neither criterion was met, Campylobacter enterocolitis was unlikely (negative predictive value 97.2%). When both criteria were met, Campylobacter enterocolitis was highly likely.

Novel association between CDKAL1 and cholesterol efflux capacity: Replication after GWAS-based discovery.

BACKGROUND AND AIMS: Although the importance of the functional properties of high-density lipoprotein (HDL) has been increasingly emphasized, studies on the genetic factors associated with HDL function are highly limited. The aim of this study was to identify genetic variants associated with an individual's cholesterol efflux capacity (CEC) using a genome-wide association study approach. METHODS: This study included a discovery group of 607 subjects with coronary artery disease and an independent replication group of 158 subjects. CEC was assessed using a radioisotope and ApoB-depleted serum. Genome-wide associations between the adjusted CEC and genotyped and imputed variants were examined with linear regression, assuming an additive genetic model. Finally, adjustments were made for confounding parameters to assess the independence of associations and to determine R2 of overall model on CEC. RESULTS: In the discovery group, 631 variants showed significant association with CEC, and five of them were found to correlate with CEC in the replication group. One of them was located near LOC541471 in 2q13, whereas the other four (rs117835232, rs117252933, rs118064592, and rs150434350) were located in CDKAL1 in 6p22.3. The association between the presence of any CDKAL1 variant and CEC was significant after adjustment for clinical and laboratory variables. High-density lipoprotein-cholesterol levels also showed a very significant association with CEC. Body mass index, current alcohol use, triglycerides levels, low-density lipoprotein-cholesterol levels and statin use showed borderline associations with CEC. CONCLUSIONS: We identified and replicated genetic variants associated with CEC using a genome-wide association study-based approach. CDKAL1 variants showed correlations with CEC independent of HDL-cholesterol levels and other clinical characteristics.

Palmitate and minimally-modified low-density lipoprotein cooperatively promote inflammatory responses in macrophages.

Increased consumption of Western-type diets and environmental insults lead to wide-spread increases in the plasma levels of saturated fatty acids and lipoprotein oxidation. The aim of this study is to examine whether palmitate and minimally modified low-density lipoprotein (mmLDL) exert an additive effect on macrophage activation. We found that CXCL2 and TNF-α secretion as well as ERK and p38 phosphorylation were additively increased by co-treatment of J774 macrophages with palmitate and mmLDL in the presence of lipopolysaccharide (LPS). Furthermore, the analysis of differentially expressed genes using the KEGG database revealed that several pathways, including cytokine-cytokine receptor interaction, and genes were significantly altered. These results were validated with real-time PCR, showing upregulation of Il-6, Csf3, Il-1ß, and Clec4d. The present study demonstrated that palmitate and mmLDL additively potentiate the LPS-induced activation of macrophages. These results suggest the existence of synergistic mechanisms by which saturated fatty acids and oxidized lipoproteins activate immune cells.

Metabolic phenotyping of human atherosclerotic plaques: Metabolic alterations and their biological relevance in plaque-containing aorta.

BACKGROUND AND AIMS: Atherosclerosis is a chronic inflammatory disease characterized by thickening of the arterial wall. However, a limited number of studies have been conducted on metabolic profiling of human aortic tissue. METHODS: We applied liquid chromatography/mass spectrometry to perform global and targeted profiling of plaque-containing aortic tissue. The aorta samples included plaque-containing (n = 18) and control plaque-free (n = 24) aortic tissue from patients undergoing aortic surgery. RESULTS: The metabolic patterns of atherosclerotic and control vessels were significantly different. Metabolites in the purine and glutathione pathways showed dysregulation of oxidative stress in plaques, and levels of glucosylceramide, tryptophan, and kynurenine, which are related to inflammation, were also altered. Interestingly, an increased level of quinic acid was observed in plaques (p < 0.000), and we demonstrated an inhibitory effect of quinic acid on inflammatory activation and oxidative stress in macrophages. CONCLUSIONS: Our study provides insight into the disease mechanism and potential markers of atherosclerosis through comprehensive metabolic profiling of human aortic tissue samples containing plaque.

Effect of two lipid-lowering strategies on high-density lipoprotein function and some HDL-related proteins: a randomized clinical trial.

BACKGROUND: The influence of lipid-lowering therapy on high-density lipoprotein (HDL) is incompletely understood. We compared the effect of two lipid-lowering strategies on HDL functions and identified some HDL-related proteins. METHODS: Thirty two patients were initially screened and HDLs of 21 patients were finally analyzed. Patients were randomized to receive atorvastatin 20 mg (n = 11) or atorvastatin 5 mg/ezetimibe 10 mg combination (n = 10) for 8 weeks. The cholesterol efflux capacity and other anti-inflammatory functions were assessed based on HDLs of the participants before and after treatment. Pre-specified HDL proteins of the same HDL samples were measured. RESULTS: The post-treatment increase in cholesterol efflux capacities was similar between the groups (35.6% and 34.6% for mono-therapy and combination, respectively, p = 0.60). Changes in nitric oxide (NO) production, vascular cell adhesion molecule-1 (VCAM-1) expression, and reactive oxygen species (ROS) production were similar between the groups. The baseline cholesterol efflux capacity correlated positively with apolipoprotein (apo)A1 and C3, whereas apoA1 and apoC1 showed inverse associations with VCAM-1 expression. The changes in the cholesterol efflux capacity were positively correlated with multiple HDL proteins, especially apoA2. CONCLUSIONS: Two regimens increased the cholesterol efflux capacity of HDL comparably. Multiple HDL proteins, not limited to apoA1, showed a correlation with HDL functions. These results indicate that conventional lipid therapy may have additional effects on HDL functions with changes in HDL proteins. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02942602 .

Granular cell tumor of the esophagus in an adolescent.

Esophageal granular cell tumor (GCT) is a rare neoplasm originating from the Schwann cells of the submucosal neuronal plexus. Histology is the gold standard for its diagnosis. Endoscopic resection or surgical excision should be considered, depending on the potential for malignancy. Here, we report a case of an esophageal GCT in an adolescent. A 12-year-old boy presented with a 1-year history of dysphagia and vomiting. Upper gastrointestinal endoscopic examination and esophagography showed narrowing of the midesophagus, and computed tomography angiography of the thoracic aorta revealed an esophageal or periesophageal mass posterior to the paratracheal segment of the esophagus. The tumor was surgically excised, and based on the pathological findings, esophageal GCT was diagnosed.

The Association between Helicobacter pylori Infection and Body Weight among Children.

PURPOSE: We performed to reveal the association between the Helicobacter pylori infection and body weight among children. METHODS: Out retrospective study included patients who underwent the H. pylori immunoglobulin G testing at Konyang University Hospital between March 2011 and June 2014. These patients were classified as seropositive (28 boys, 27 girls; mean age: 9.89±3.28 years) or seronegative (55 boys, 54 girls; mean age: 9.84±3.02 years). Next, we compared various characteristics between the seropositive and negative groups, as well as between obese children (body weight ≥90th percentile) and non-obese children (body weight <90th percentile). Furthermore, we compared the change in body weight after 2 months of treatment with amoxicillin, clarithromycin and omeprazole among the 55 seropositive children (14 treated children and 41 non-treated children). RESULTS: There were no differences in the weights and laboratory data for the 55 seropositive children and 109 seronegative children (weight; 40.96±18.11 kg vs. 36.85±13.72 kg, respectively; p=0.14). And, there was no difference in the prevalence of H. pylori infection among the 29 obese and 135 non-obese children (p=0.581). However, after 2 months of eradication, the 14 treated patients exhibited a significant weight gain (+0.91±0.52 kg), compared to the 41 non-treated patients (-0.29±1.16 kg, p=0.025). CONCLUSION: Our findings present that obesity was not associated with the H. pylori infection, although H. pylori eradication led to significant increase in body weight.

Fibronectin fragment-induced expression of matrix metalloproteinases is mediated by MyD88-dependent TLR-2 signaling pathway in human chondrocytes.

INTRODUCTION: Fibronectin fragments (FN-fs) are increased in the cartilage of patients with osteoarthritis (OA) and have a potent chondrolytic effect. However, little is known about the cellular receptors and signaling mechanisms that are mediated by FN-fs. We investigated whether the 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) regulates cartilage catabolism via the Toll-like receptor (TLR)-2 signaling pathway in human chondrocytes. METHODS: Small interfering RNA was used to knock down TLR-2 and myeloid differentiation factor 88 (MyD88). TLR-2 was overexpressed in chondrocytes transfected with a TLR-2 expression plasmid. The expression levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were analyzed using quantitative real-time reverse transcription polymerase chain reactions, immunoblotting, or enzyme-linked immunosorbent assay. The effect of TLR-2 on 29-kDa FN-f-mediated signaling pathways was investigated by immunoblotting. RESULTS: TLR-2, TLR-3, TLR-4, and TLR-5 mRNA were significantly overexpressed in OA cartilage compared with normal cartilage, whereas no significant difference of TLR-1 mRNA expression was found. 29-kDa FN-f significantly increased TLR-2 expression in human chondrocytes in a dose- and time-dependent manner. Knockdown of TLR-2 or MyD88, the latter a downstream adaptor of TLR-2, significantly inhibited 29-kDa FN-f-induced MMP production at the mRNA and protein levels. Conversely, TLR-2 overexpression led to enhanced MMP production by 29-kDa FN-f. In addition, TLR-2 knockdown apparently inhibited 29-kDa FN-f-mediated activation of phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, and p38, but not of c-Jun N-terminal kinase or extracellular signal-regulated kinase. Exposure to synovial fluid (SF) from affected joints of patients with OA elevated MMP-1, MMP-3, and MMP-13 expression markedly in primary chondrocytes without reducing cell viability. However, TLR-2 knockdown in chondrocytes significantly suppressed SF-induced MMP induction. CONCLUSIONS: Our data demonstrate that the MyD88-dependent TLR-2 signaling pathway may be responsible for 29-kDa FN-f-mediated cartilage catabolic responses. Our results will enhance understanding of cartilage catabolic mechanisms driven by cartilage degradation products, including FN-f. The modulation of TLR-2 signaling activated by damage-associated molecular patterns, including 29-kDa FN-f, is a potential therapeutic strategy for the prevention of cartilage degradation in OA.

Fecal calprotectin concentration in neonatal necrotizing enterocolitis.

PURPOSE: Among the many factors associated with acute intestinal mucosal infection, numerous studies have proposed the usefulness of fecal calprotectin. The aim of this study was to evaluate the usefulness of fecal calprotectin in the diagnosis of necrotizing enterocolitis (NEC). METHODS: We collected 154 stool samples from 16 very low birth weight and premature newborns at the Konyang University Hospital neonatal intensive care unit or neonatal nursery. The stool samples were collected using the Calprest device, and the fecal calprotectin level was measured with the BÜHLMANN Calprotectin enzyme-linked immunosorbent assay kit. RESULTS: Fecal calprotectin levels were significantly higher in the NEC group than in the non-NEC group (P=0.02). There was a significant positive linear relationship between the fecal calprotectin level and number of days after birth (P=0.00) in the gestational age <26 weeks group. There was a significant negative linear relationship between the calprotectin level and number of days after birth (P=0.03) in the gestational age ≥26 weeks and <30 weeks group. There was no difference in the calprotectin levels according to the type and method of feeding between the NEC and non-NEC groups. CONCLUSION: Fecal calprotectin levels were significantly increased in premature infants with NEC. The fecal calprotectin test is a noninvasive, easy, and useful tool for the diagnosis of NEC.

Increase in Aminotransferase Levels during Urinary Tract Infections in Children.

PURPOSE: The aim of this study was to evaluate the prevalence of increased aminotransferase levels and to identify associated factors in children admitted to hospital with urinary tract infections (UTIs). METHODS: The study included children with a diagnosis of UTI who were admitted to the Konyang University Hospital from January 2007 to May 2011. The total number of patients was 249 and the mean age was 15.88±28.21 months. UTI was defined as a positive urine culture (>10(5)/colony forming unit [CFU]) with pyrexia. Patients were treated by intravenous antibiotics, such as ampicillin/sulbactam, aminoglycoside, cephalosporins or vancomycin. Patients with neonatal jaundice or other liver disease were excluded. We investigated the relationship of aminotransferase levels with the type of antibiotic, degree of vesicoureteral reflux (VUR), and causative organisms. RESULTS: Children with increased aminotransferase levels were younger than those with normal levels (p=0.001), but white blood cell count, platelet count, causative organisms, type of antibiotics and presence of VUR were not associated with aminotransferase levels. Aminotransferase levels became normal within 1 month after discharge without special measures, except in 1 case. CONCLUSION: We found that many children with UTI have abnormal aminotransferase levels. In most cases, this change is mild and self-limiting. We conclude that increased aminotransferase level increase during UTI do not require unnecessary tests and excessive treatment.

MicroRNA-127-5p regulates matrix metalloproteinase 13 expression and interleukin-1ß-induced catabolic effects in human chondrocytes.

OBJECTIVE: MicroRNAs (miRNAs), small noncoding RNA molecules, are involved in the pathogenesis of various diseases such as cancer and arthritis. The aim of this study was to determine whether miR-127-5p regulates interleukin-1ß (IL-1ß)-induced expression of matrix metalloproteinase 13 (MMP-13) and other catabolic factors in human chondrocytes. METHODS: Expression of miR-127-5p and MMP-13 by normal and osteoarthritic (OA) human cartilage was determined using real-time polymerase chain reaction. The effect of miR-127-5p on MMP-13 expression was evaluated using transient transfection of human chondrocytes or chondrogenic SW-1353 cells with miR-127-5p or its antisense inhibitor (anti-miR-127-5p). MMP-13 protein production was quantified by enzyme-linked immunosorbent assay, and the involvement of miR-127-5p in IL-1ß-mediated catabolic effects was examined by immunoblotting. MicroRNA-127-5p binding with the putative site in the 3'-untranslated region (3'-UTR) of MMP-13 messenger RNA (mRNA) was validated by luciferase reporter assay. RESULTS: There was a significant reduction in miR-127-5p expression in OA cartilage compared with normal cartilage. Up-regulation of MMP-13 expression by IL-1ß was correlated with down-regulation of miR-127-5p expression in human chondrocytes. MicroRNA-127-5p suppressed IL-1ß-induced MMP-13 production as well as the activity of a reporter construct containing the 3'-UTR of human MMP-13 mRNA. In addition, mutation of the miR-127-5p binding site in the 3'-UTR of MMP-13 mRNA abolished miR-127-5p-mediated repression of reporter activity. Conversely, treatment with anti-miR-127-5p remarkably increased reporter activity and MMP-13 production. Interestingly, the IL-1ß-induced activation of JNK, p38, and NF-κB and expression of MMP-1 and cyclooxygenase 2 were significantly inhibited by miR-127-5p. CONCLUSION: MicroRNA-127-5p is an important regulator of MMP-13 in human chondrocytes and may contribute to the development of OA.