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Background/Aims Connective tissue growth factor (CTGF) is a profibrotic factor implicated in pressure overload-mediated myocardial fibrosis. In this study, we determined the role of predicted CTGF-targeting microRNAs (miRNAs) in rat models of aortic stenosis and reverse cardiac remodeling. Methods Minimally invasive ascending aortic banding was performed in 24 7-week-old male Sprague-Dawley rats, which were divided into three groups. The banding group consisted of eight rats that were sacrificed immediately after 6 weeks of aortic constriction. The debanding group underwent aortic constriction for 4 weeks and was sacrificed 2 weeks after band removal. The third group underwent sham surgery. We investigated the expression of CTGF, transforming growth factor-β1 (TGFβ1), and matrix metalloproteinase-2 using ELISA and examined miRNA-26b, miRNA-133a, and miRNA-19b as predicted CTGF-targeting miRNAs based on miRNA databases in 24-hour TGFβ-stimulated and TGFβ- washed fibroblasts and myocardial tissues from all subjects. Results CTGF was elevated in 24-hour TGFβ-stimulated fibroblasts and decreased in 24-hour TGFβ-washed fibroblasts. miRNA-26b was significantly increased in TGFβ-washed fibroblasts compared with control and TGFβ-stimulated fibroblasts (p < 0.05). CTGF expression was significantly higher in the banding group than that in the sham and debanding groups. The relative expression levels of miRNA-26b were higher in the debanding group than in the banding group. Conclusions The results of our study using models of aortic banding and debanding suggested that miRNA-26b was significantly increased after aortic debanding. The in vitro model yielded the same results: miRNA-26b was upregulated after removal of TGFβ from fibroblasts.

Background and Aims Endoscopic submucosal dissection (ESD) is considered technically difficult and challenging using a conventional flexible endoscope, mainly due to the lack of proper countertraction to expose the submucosal dissection plane. This study aimed to evaluate the feasibility of a traction method using a dexterous robotic arm in ex vivo gastric ESD. Methods ESD was performed in a total of 45 procedures using a portable endoscopic tool handler (PETH) (n = 30) and using the conventional method (n = 15) at various locations in the stomach. For each procedure, the performance data were recorded, including the total procedure time (minutes), incision time (minutes), dissection speed (mm2/minute), and blind dissection rate (%), to enable a comparison of the 2 ESD methods. Results The total procedure time was significantly shorter with PETH-ESD than in conventional ESD (23 vs 36 minutes, P = .011). This result is mainly attributed to the dissection speed, which was significantly faster, by more than 2.5 times, using the PETH (122.3 ± 76.5 vs 47.5 ± 26.9 mm2/minute, P Conclusions The countertraction method using the PETH significantly improved the dissection speed and reduced blind dissection by enhancing direct visualization of the submucosal plane. With the advantages of multidirectional traction, fine tension control, and regrasping, this new device is expected to improve the performance of ESD and further facilitate advanced endoscopic procedures.

Secondary hyperparathyroidism (SHPT) is characterized by excessive serum parathyroid hormone levels in response to decreasing kidney function, and tertiary hyperparathyroidism (THPT) is often the result of a long-standing SHPT. To date, several genes have been associated with the pathogenesis of primary hyperparathyroidism (PHPT). However, the molecular genetic mechanisms of uremic hyperparathyroidism (HPT) remain uncharacterized. To elucidate the differences in genetic alterations between PHPT and SHPT/THPT, the targeted next-generation sequencing of genes associated with HPT was performed using DNA extracted from parathyroid tissues. As a result, 26 variants in 19 PHPT or SHPT/THPT appeared as candidate pathogenic mutations, which corresponded to 9 (35%) nonsense, 8 (31%) frameshift, 6 (23%) missense, and 3 (11%) splice site mutations. The MEN1 (23%, 6/26), ASXL3 (15%, 4/26), EZH2 (12%, 3/26), and MTOR (8%, 2/26) genes were frequently mutated. Sixteen of 25 patients with PHPT (64%) had one or more mutations, whereas 3 (21%) of 21 patients with SHPT/THPT had only 1 mutation (p = 0.001). Sixteen of 28 patients (57%) with parathyroid adenoma (PA) had one or more mutations, whereas 3 of 18 patients (17%) with parathyroid hyperplasia (PH) had just one mutation (p = 0.003). Known driver mutations associated with parathyroid tumorigenesis such as CCND1/PRAD1, CDC73/HRPT2, and MEN1 were identified only in PA (44%, 7/16 with mutations). Our results suggest that molecular genetic abnormalities in SHPT/THPT are distinct from those in PHPT. These findings may help in analyzing the molecular pathogenesis underlying uremic HPT development.

Background: Thoracic impedance monitoring able to detect pneumonia in the very early phase of emerging infiltration prior the patient developed remarkable clinical symptoms. However, no studies have yet been conducted on the usefulness of predicting pneumonia patient outcomes with parameters from electrical cardiometry. Objective: In the present study, we evaluated whether parameters measured by electrical cardiometry can predict clinical outcomes including mortality and length of hospital stay in patients with community-acquired pneumonia in the emergency department. Methods: Demographic, clinical and laboratory data were collected from enrolled patient. Electrical cardiometry monitoring was done with a portable electrical cardiometry device connected to the body surface sensor. The continuous data from electrical cardiometry were recorded, and parameters were stored on the electrical cardiometry device automatically and then the data were downloaded for further analysis. Results: Thoracic fluid content has shown to be significantly higher in the intensive care unit admission group and in the death group. Expired patients had higher value of thoracic fluid content at emergency department admission. From a receiver operating characteristics curve analysis, thoracic fluid content presented fair AUC values of 0.72 (95% confidence interval, 0.71–0.74) and 0.73 (0.62–0.82) for prediction of 28-day mortality and intensive care unit admission. Arterial partial pressure of oxygen (PaO2), the ratio of arterial partial pressure of oxygen to inspired oxygen fraction (PaO2/FiO2 ratio) also showed excellent AUC value for prediction of mortality and intensive care unit admission. Conclusion: Electrical cardiometry monitoring indicated new possibility to anticipate prognosis of community-acquired pneumonia patient. Increased thoracic fluid content value would relate worse outcome of the patient like mortality and intensive care unit admission. Electrical cardiometry monitoring allows real-time measurements of thoracic fluid content without restraining the patient or invasive catheters.

We have found that early corticosteroid therapy was effective for reducing morbidity during five Korea-wide epidemics. We evaluated the clinical and laboratory parameters of 56 children who received early corticosteroid treatment for pneumonia that was caused by macrolide-resistant Mycoplasma pneumoniae (M. pneumoniae) or macrolide-sensitive M. pneumoniae between July 2019 and February 2020. All subjects had dual positive results from a PCR assay and serological test, and received corticosteroids within 24–36 h after admission. Point mutation of residues 2063, 2064, and 2067 was identified in domain V of 23S rRNA. The mean age was 6.8 years and the male:female ratio was 1.2:1 (31:25 patients). Most of the subjects had macrolide-resistant M. pneumoniae (73%), and all mutated strains had the A2063G transition. No significant differences in clinical and laboratory parameters were observed between macrolide-resistant and macrolide-sensitive M. pneumoniae groups that were treated with early dose-adjusted corticosteroids. Higher-dose steroid treatment may be needed for patients who have fever that persists for &gt, 48 h or increased biomarkers such as lactate dehydrogenase concentration at follow-up despite a usual dose of steroid therapy.

Objective This study investigated the ability of implanted human nasal inferior turbinate-derived mesenchymal stem cells (hTMSCs) to repair injured vocal folds. To this end, we used quantitative real-time polymerase chain reaction (PCR) to analyze the early phase of wound healing and histopathological analysis to explore the late phase of wound healing in xenograft animal models. Study Design Prospective animal study. Setting Research laboratory. Subjects and Methods The right-side lamina propria of the vocal fold was injured in 20 rabbits and 30 rats. Next, hTMSCs were implanted into half of the injured vocal folds (hTMSC groups). As a control, phosphate-buffered saline (PBS) was injected into the other half of the injured vocal folds (PBS groups). Rat vocal folds were harvested for polymerase chain reaction (PCR) at 1 week after injury. Rabbit vocal folds were evaluated endoscopically and the larynges harvested for histological and immunohistochemical examination at 2 and 8 weeks after injury. Results In the hTMSC group, PCR showed that hyaluronan synthase ( HAS) 1, HAS 2, and transforming growth factor ( TGF)-β1 were significantly upregulated compared with the PBS group. Procollagen type III ( COL III) messenger RNA expression was significantly upregulated in the PBS group compared with the normal group. Histological analyses showed that hTMSC administration afforded more favorable collagen and hyaluronic acid deposition than was evident in the controls. Implanted hTMSCs were observed in injured vocal folds 2 weeks after implantation. Conclusions Our results show that hTMSCs implantation into injured vocal folds facilitated vocal fold regeneration, with presenting antifibrotic effects.

Background and objective To assess the effects of hypercholesterolemia (HC) on the quality of erections and to evaluate the effects of stain therapy in a rat model of erectile dysfunction (ED) induced by HC. Material and methods Sprague–Dawley rats were randomly divided into three groups (n=12 in each): control, HC, and HC with simvastatin treatment (HC+SS). The control was fed a normal chow diet, and the HC and HC+SS were fed a high-fat and high-cholesterol diet for 12 weeks. The HC+SS received simvastatin once daily via oral gavage for 12 weeks. Subsequently, the intraperitoneal glucose tolerance test (IPGTT), intra-cavernous pressure and mean arterial pressure, lipid profiles, expression of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS), oxidative stress (8-hydroxy-2-deoxygua-nosine, 8-OHdG level), serum testosterone levels, and the ratio of collagen fibers (CF) and smooth muscle (SM) were evaluated in the serum and corpora tissue. Results IPGTT was not different among all groups. The HC showed markedly lower erectile parameters than the control. In contrast, the HC+SS showed preserved erectile function, improved lipid profiles, increased eNOS and nNOS, decreased oxidative stress, and minimized change in SM/CF ratio. Conclusions Our results suggest that oxidative stress damage by HC may cause ED and that statin therapy may have beneficial effects on preserving erectile function by improving lipid profiles and minimizing dam-age caused by oxidative stress.

Purpose: To investigate the effect of topical motesanib, an inhibitor of receptor tyrosine kinase, on experimental choroidal neovascularization (CNV). Methods: CNV was induced in 46 nine-week-old male C57BL/6 mice using fundus laser photocoagulation. The right eye of each mouse was treated with motesanib eye drop (4 times daily) and the left eye with vehicle eye drop (4 times daily) for 14 days. To evaluate changes in the CNV lesions, fluorescein angiography, immunofluorescence staining with CD34, and histological examinations were performed 14 days after CNV induction. The expression of phosphorylated extracellular signal-regulated kinase (ERK1/2) in choroidal tissues was determined using western blot analysis to demonstrate the inhibitory effect of topically administered motesanib on intracellular signaling pathways involved in CNV development. Results: Fluorescein angiography showed that fluorescence leakage in eyes treated with topical motesanib was significantly less than in mice treated with vehicle (P=0.01). On immunofluorescence staining, the CD34-labeled area was smaller in topical motesanib-treated eyes (P

The protective mechanism of paricalcitol remains unclear in renal ischemia-reperfusion (IR) injury. We investigated the renoprotective effects of paricalcitol in IR injury through the prostaglandin E2 (PGE2) receptor EP4. Paricalcitol was injected into IR-exposed HK-2 cells and mice subjected to bilateral kidney ischemia for 23 min and reperfusion for 24 hr. Paricalcitol prevented IR-induced cell death and EP4 antagonist cotreatment offset these protective effects. Paricalcitol increased phosphorylation of Akt and cyclic AMP responsive element binding protein (CREB) and suppressed nuclear factor-κB (NF-κB) in IR-exposed cells and cotreatment of EP4 antagonist or EP4 small interfering RNA blunted these signals. In vivo studies showed that paricalcitol improved renal dysfunction and tubular necrosis after IR injury and cotreatment with EP4 antagonist inhibited the protective effects of paricalcitol. Phosphorylation of Akt was increased and nuclear translocation of p65 NF-κB was decreased in paricalcitol-treated mice with IR injury, which was reversed by EP4 blockade. Paricalcitol decreased oxidative stress and apoptosis in renal IR injury. Paricalcitol also attenuated the infiltration of inflammatory cells and production of proinflammatory cytokines after IR injury. EP4 antagonist abolished these antioxidant, anti-inflammatory, and antiapoptotic effects. The EP4 plays a pivotal role in the protective effects of paricalcitol in renal IR injury.

Hepatocellular carcinoma (HCC) is an aggressive malignancy with a poor prognosis and a very complex dysregulated molecular etiology. Furthermore, conventional therapy thus far has had only limited success. A recently developed oral multikinase inhibitor, sorafenib, has been used to improve survival in HCC patients, however, follow‑up studies have revealed a high rate of cancer recurrence. Therefore, identification of genes involved in sorafenib resistance is urgently required. RNA interference (RNAi) is a powerful tool for performing loss-of-function genetic screens and can facilitate the identification of components of the cellular signaling pathway. This study describes the results of an unbiased genomic screening using RNAi in an HCC cell line to elucidate genes related to sorafenib non-responsiveness or resistance. A genome-wide in vitro RNA interference screen revealed the role of suppressor of morphogenesis in genitalia-1 (SMG-1) as a determinant of sorafenib resistance. The inhibition of SMG-1 reduced sorafenib sensitivity in the studied HCC cell lines. An immunohistochemical comparison of cancerous and non‑cancerous regions showed strong staining in the non‑neoplastic hepatocyte regions of HCC. SMG-1 may warrant investigation as an agent to reverse sorafenib resistance.

*Corresponding author: Mi Kyung Kim, MD Department of Pediatrics, Presbyterian Medical Center, University of Seonam College of Medicine, 365 Seowon-ro, Wansan-gu, Jeonju 560-750, Korea Tel: +82-63-230-1390 Fax: +82-63-230-1490 E-mail: kmik7@hanmail.net Purpose: The purpose of this study was to determine the incidence of depression in families with hemophiliac patients and associated factors. Methods: The survey respondents were the family members of 37 hemophiliac patients who visited our hospital between September 2013 and January 2014. The survey questionnaire included questions on the general characteristics of the hemophiliac patients and the family members, and the Beck depression inventory (BDI) scale for evaluating depression. Results: The mean age of the family members of the patients was 41.2 years. The mother was the main caregiver for 16 patients (43.2%). The percentages of patients with severe hemophilia (less than 1% factor VIII or IX activity), hepatitis C virus infection, and joint disorders were 67.6%, 13.5%, and 21.6%, respectively. The mean± SD BDI score of the family members of the patients was 6.7± 7.1 points, and 29.7% of the family members of the patients were found to have a tendency toward depression (≥10 points). The higher the severity of hemophilia in the patients, the higher the incidence of depression in their families (P= 0.035). Conclusion: About 30% of the families with hemophiliac patients were found to have a tendency toward depression. The risk for depression increased with the severity of hemophilia. Family members of hemophiliac patients often experience stress and burden. Therefore, there is a need to mobilize social resources in order to share the burden of these families and to provide continuous and comprehensive care for family members.

The functional unit of the thyroid gland, the thyroid follicle, dynamically responds to various stimuli to maintain thyroid hormone homeostasis. However, thyroid follicles in the adult human thyroid gland have a very limited regenerative capacity following partial resection of the thyroid gland. To gain insight into follicle regeneration in the adult thyroid gland, we observed the regeneration processes of murine thyroid follicles after partial resection of the lower third of the thyroid gland in 10-week-old male C57BL/6 mice. Based on sequential observation of the partially resected thyroid lobe, we found primitive follicles forming in the area corresponding to the central zone of the intact lateral thyroid lobe. The primitive thyroid follicles were multiciliated and had coarsely vacuolated cytoplasm and large vesicular nuclei. Consistently, these primitive follicular cells did not express the differentiation markers paired box gene-8 and thyroid transcription factor-1 (clone SPT24), but were positive for forkhead box protein A2 and leucine-rich repeat-containing G-protein-coupled receptor 4/GPR48. Follicles newly generated from the primitive follicles had clear or vacuolar cytoplasm with dense, darkly stained nuclei. At day 21 after partial thyroidectomy, the tall cuboidal follicular epithelial cells had clear or vacuolar cytoplasm, and the intraluminal colloid displayed pale staining. Smaller activated follicles were found in the central zone of the lateral lobe, whereas larger mature follicles were located in the peripheral zone. Based on these observations, we propose that the follicle regeneration process in the partially resected adult murine thyroid gland associated with the appearance of primitive follicular cells may be a platform for the budding of differentiated follicles in mice.

To investigate the effects of axitinib, an inhibitor of vascular endothelial growth factor receptors, on choroidal neovascularization (CNV) in an animal model of neovascular age-related macular degeneration (AMD).Experimental CNV lesions were induced in C57BL/6 mice by laser photocoagulation. Beginning 1 day after CNV induction, mice were treated with axitinib (5 mg/kg/day) or vehicle for 2 weeks. In other groups of mice, axitinib or vehicle treatment was started 7 days after the laser application to determine the effect of the drug on established CNV. Untreated mice were used as a baseline group. Two weeks after laser injury, the extent of CNV was assessed from choroidal flat mounts perfused with fluorescein-labeled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the CNV lesions.Orally administered axitinib inhibited CNV growth in the laser-induced CNV model. Axitinib caused a 70.1% inhibition of CNV lesions compared to vehicle-treatment (p0.001). Axitinib also caused a significant regression of established CNV, reducing the area by 71.1% compared to vehicle treatment (p0.001). Moreover, immunofluorescence staining showed that the area of isolectin IB4 labeled vessels was smaller in the axitinib-treated group compared to the vehicle-treated group (p0.001).Axitinib effectively inhibits the progression of CNV in an experimental animal model. These results suggest that axitinib could constitute a therapeutic alternative for the treatment of neovascular AMD.

Carcinoma ex pleomorphic adenoma (CXPA) is a rare, aggressive, poorly understood malignancy that usually occurs in the salivary glands. CXPA has been reported to account for 3.6% of all salivary neoplasms and 11.7% of salivary malignancies. CXPA not only has a low incidence rate but there are few papers or case reports reporting perineural invasion rates. We report a case of CXPA which occurred in the parotid gland, showing retrograde perineural invasion along the facial nerve back to the internal auditory canal (IAC).

Exenatide has beneficial effects on insulin sensitivity in several animal models; however, its mechanism of action remains unclear. Furthermore, the relationship between the effect of exenatide on the changes in the relative abundance of microRNAs (miRNAs), which play a role in regulating glucose and lipid metabolism, is not fully understood. Therefore, we assessed the effect of exenatide on miRNA expression in a high-fat diet (HFD)-induced mouse model of obesity. Both HFD control and exenatide-treated HFD mice showed similar body weight gain and increase in β-cell mass. Insulin levels were significantly lower in exenatide-treated mice than in HFD control mice. The levels of miRNA-15a, 29c, 124a, and 375 in the pancreas were significantly increased in HFD control mice. Furthermore, the levels of miRNA-29c, 124a, and 146a in the liver and miRNA-15a, 29c, 124a, and 146a in the muscle were significantly increased. In contrast, the levels of miRNA-15a, 29c, 124a, and 375 in the serum were significantly decreased. These effects were reversed by treatment with exenatide. Our results provide experimental evidence that exenatide-mediated amelioration of insulin sensitivity is associated with antagonistic changes in the relative abundance of miRNA-15a, 29c, 124a, and 375 in tissues and serum, thus highlighting their usefulness as biomarkers for monitoring insulin sensitivity and response to exenatide treatment in experimental diabetes.

Context: The oncogenic RET/PTC tyrosine kinase causes papillary thyroid cancer (PTC). The use of inhibitors specific for RET/PTC may be useful for targeted therapy of PTC. Objective: The objective of the study was to evaluate the efficacies of the recently developed kinase inhibitors SU11248, SU5416, and SU6668 in inhibition of RET/PTC. Design: SU11248, SU5416, and SU6668 were synthesized, and their inhibitory potencies were evaluated using an in vitro RET/PTC kinase assay. The inhibitory effects of the compounds on RET/PTC were evaluated by quantifying the autophosphorylation of RET/PTC, signal transducer and activator of transcription (STAT)-3 activation, and the morphological reversal of RET/PTC-transformed cells. Results: An in vitro kinase assay revealed that SU5416, SU6668, and SU11248 inhibited phosphorylation of the synthetic tyrosine kinase substrate peptide E4Y by RET/PTC3 in a dose-dependent manner with IC50 of approximately 944 nm for SU5416, 562 nm for SU6668, and 224 nm for SU11248. Thus, SU11248 effectively inhibits the kinase activity of RET/PTC3. RET/PTC-mediated Y705 phosphorylation of STAT3 was inhibited by addition of SU11248, and the inhibitory effects of SU11248 on the tyrosine phosphorylation and transcriptional activation of STAT3 were very closely correlated with decreased autophosphorylation of RET/PTC. SU11248 caused a complete morphological reversion of transformed NIH-RET/PTC3 cells and inhibited the growth of TPC-1 cells that have an endogenous RET/PTC1. Conclusion: SU11248 is a highly effective tyrosine kinase inhibitor of the RET/PTC oncogenic kinase.

Anaplastic thyroid carcinomas are a highly aggressive and extremely lethal form of human cancer, but the biological characteristics related to their aggressive nature are not understood. Moreover, Gadd45 family proteins have been implicated in a variety of growth-regulatory mechanisms, including DNA replication and repair, G(2)/M checkpoint control, and apoptosis. In this study we found that Gadd45gamma RNA was present at significantly lower levels in anaplastic cancer cells, compared with normal primary cultured thyrocytes. In addition, the adenovirus-mediated reexpression of Gadd45gamma significantly inhibited the proliferation of anaplastic thyroid carcinoma cells, ARO, FRO, and NPA cells, which was attributed to apoptosis. Furthermore, the adenovirus-mediated delivery of Gadd45gamma gene in anaplastic thyroid cancer resulted in the inhibition of tumor growth in vivo. This in vitro and in vivo activity of the adenovirus-mediated transduction of CR6/Gadd45gamma, on anaplastic thyroid cancer cell growth suppression, was reminiscent of the effects of p53. This study demonstrates that the Gadd45gamma gene has potential use as a candidate gene for gene therapy in anaplastic thyroid cancer.

Impaired mitochondrial oxidative phosphorylation (OXPHOS) has been proposed as an etiological mechanism underlying insulin resistance. However, the initiating organ of OXPHOS dysfunction during the development of systemic insulin resistance has yet to be identified. To determine whether adipose OXPHOS deficiency plays an etiological role in systemic insulin resistance, the metabolic phenotype of mice with OXPHOS–deficient adipose tissue was examined. Crif1 is a protein required for the intramitochondrial production of mtDNA–encoded OXPHOS subunits; therefore, Crif1 haploinsufficient deficiency in mice results in a mild, but specific, failure of OXPHOS capacity in vivo. Although adipose-specific Crif1-haploinsufficient mice showed normal growth and development, they became insulin-resistant. Crif1-silenced adipocytes showed higher expression of chemokines, the expression of which is dependent upon stress kinases and antioxidant. Accordingly, examination of adipose tissue from Crif1-haploinsufficient mice revealed increased secretion of MCP1 and TNFα, as well as marked infiltration by macrophages. These findings indicate that the OXPHOS status of adipose tissue determines its metabolic and inflammatory responses, and may cause systemic inflammation and insulin resistance., Author Summary Type 2 diabetes is one of the most challenging health problems in the 21st century. Although insulin resistance is regarded as a fundamental defect that precedes the development of type 2 diabetes, the nature and cause of insulin resistance remain unknown. Adipose tissue is an important organ that determines whole-body energy metabolism, and its dysfunction is a critical element in the development of systemic insulin resistance. Adipose mitochondrial function is suppressed in the insulin-resistant state, and increased adipose mitochondrial biogenesis is associated with the reversal of insulin resistance by a PPARγ agonist. However, despite these important observations, little is known about how mitochondrial respiratory dysfunction in white adipose tissue (WAT) causes insulin resistance. To determine whether adipose deficiency of mitochondrial respiratory capacity plays an etiological role in systemic insulin resistance, the metabolic phenotype of mice with mitochondrial OXPHOS (oxidative phosphorylation)–deficient adipose tissue was examined. Crif1 is a protein required for the translation of mtDNA–encoded OXPHOS subunits. Interestingly, mice haploinsufficient for Crif1 in adipose tissue showed reduced OXPHOS capacity and developed marked insulin resistance.

BACKGROUND The effect of paricalcitol on renal ischemia-reperfusion injury (IRI) has not been investigated. We examined whether paricalcitol is effective in preventing inflammation in a mouse model of IRI, and evaluated the cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) pathways as a protective mechanism of paricalcitol. METHODS Paricalcitol (0.3 μg/kg) was administered to male C57BL/6 mice 24 h before IRI. Bilateral kidneys were subjected to 23 min of ischemia, and mice were killed 72 h after IRI. The effects of paricalcitol on renal IRI were evaluated in terms of renal function, tubular necrosis, apoptotic cell death, inflammatory cell infiltration and inflammatory cytokines. The effects of paricalcitol on COX-2, PGE2 and its receptors were investigated. RESULTS Paricalcitol pretreatment improved renal function (decreased blood urea nitrogen and serum creatinine levels), tubular necrosis and apoptotic cell death in IRI-mice kidneys. The infiltration of inflammatory cells (T cells and macrophages), and the production of proinflammatory cytokines (RANTES, tumor necrosis factor-α, interleukin-1β and interferon-γ) were reduced in paricalcitol-treated mice with IRI. Paricalcitol up-regulated COX-2 expression, PGE2 synthesis and mRNA expression of receptor subtype EP4 in post-ischemic renal tissue. The cotreatment of a selective COX-2 inhibitor with paricalcitol restored functional injury and tubular necrosis in paricalcitol-treated mice with IRI. CONCLUSIONS Our study demonstrates that paricalcitol pretreatment prevents renal IRI via the inhibition of renal inflammation, and the up-regulation of COX-2 and PGE2 is one of the protective mechanisms of paricalcitol in renal IRI.

Background: This study was conducted to evaluate the effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of laser-induced choroidal neovascularization. Methods: Choroidal neovascularization was induced in C57BL/6 mice by rupturing Bruch's membrane using laser photocoagulation. Following laser injury, the mice were divided into three groups and administered either vehicle, 1 mg/kg or 5 mg/kg of cediranib daily by oral gavage for 2 weeks. Two weeks after laser injury, the area of choroidal neovascularization lesions was measured by choroidal flat mounts using fluorescein-labelled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the choroidal neovascularization lesions. Results: Choroidal flat mount analysis revealed that orally administered cediranib reduced the extent of choroidal neovascularization. The groups treated with 1 and 5 mg/kg/day showed 57.2 and 66.0% reduction of choroidal neovascularization lesions, respectively, compared with the control group treated with vehicle alone (P = 0.012). The size of the fluorescently labelled choroidal neovascularization complex in cediranib-treated groups was much smaller than that from vehicle-treated group (P = 0.035). Conclusions: Cediranib inhibited laser-induced choroidal neovascularization in mice and may have therapeutic potential for patients with neovascular age-related macular degeneration.

Objective To evaluate the safety and potential efficacy of “recombinant human growth hormone (rhGH)” on the functional recovery of completed stroke patients. Method Completed stroke patients were recruited. All participants were randomly assigned to the GH group (rhGH injection and rehabilitative therapy) or the control group (only rehabilitative therapy). Above all, they were closely monitored for safety. Further, for the efficacy measurement, Korean Modified Barthel Index (K-MBI), Manual Muscle strength Test (MMT), and Fugl-Meyer assessment (FMA) were assessed to determine the changes of functional recovery during 6-months of the study period. Along with it, diffusion tensor image was taken as the baseline, and a followed-up study to observe the changes in diffusion tensor tractography (DTT), during the period, and one patient in the GH group was also examined with functional MRI (fMRI). Index of fatigue on 5 point scale for the study period was also assessed. Results Twenty-two patients were enrolled, and 15 completed the study and were included in the analysis. No harmful adverse events were observed in the GH group. By comparison between the groups, the GH group showed more improvement in K-MBI than the control group (p

목적: 본 연구는 최근 10년 동안 전주 예수병원에 쯔쯔가무시병으로 입원한 환자를 조사하여 소아와 성인의 임상 양상을 비교하고자 하였다. 방법: 2003년 1월부터 2012년 12월까지, 쯔쯔가무시병의 진단 기준에 포함되는 768명의 환자를 후향적으로 검토하여, 소아 49명, 성인 719명의 임상적 특징과 검사소견 및 합병증 등을 분석 비교하였다. 결과: 연도별 환자의 증가 추세는 소아와 성인 모두에서 뚜렷하게 보이지 않았고, 10월과 11월에 환자가 가장 많이 발생하였다. 남녀비에서 소아는 남아가 많은 반면에, 성인은 여자가 많았고, 거주 지역은 소아가 성인에 비해 도시가 더 많았다. 증상은 소아에서 발진과 가피가 많았고, 근육통은 성인에서 더 많았다. 검사상 소아는 빈혈이 많은 반면에, 혈소판, 간기능, 신기능의 이상 소견이 적었다. 입원 기간과 합병증에서는 성인보다 양호한 결과를 보였다. 소아에서 독시사이클린과 마크로라이드계열 항생제의 치료 효과를 비교하였을 때, 두 약제 간에 유의한 차이는 보이지 않았다. 결론: 쯔쯔가무시병 환자에서 소아는 남아에서 많았고, 발진 및 가피의 발생이 더 많았다. 검사상 이상 소견은 성인에 비해 경하였으며, 입원 기간이 짧고, 합병증이 적으며, 마크로라이드계열 항생제에도 동일한 치료 효과를 보였다. 따라서 유행 시기에, 소아에서 쯔쯔가무시병이 의심될 때에는, 세밀한 이학적 진찰과 혈청학적 검사를 실시하여 빠른 진단을 내릴 수 있도록 노력해야 하며, 상대적으로 부작용이 적은 마크로라이드계 항생제로도 좋은 치료 결과를 기대해 볼 수 있다. 【Purpose: We compared the clinical manifestations of patients with tsutsugamushi disease between children and adults. Methods: From January 2003 to December 2012, 768 patients diagnosed with tsutsugamushi disease were retrospectively reviewed, and the clinical characteristics, laboratory findings, and complications were compared between children and adults. Results: No patterns of annual increases in the number of patients were noted in both children and adults. The higher incidences occurred in October and November respectively. By gender, male outnumbered female in children, but the opposite trend was seen in adults. By residential area, the urban distribution of children was higher than that of adults. Rashes (P =0.001) and eschar (P =0.004) were more common in children, while myalgia was more common in adults. Children had a high prevalence of anemia (P =0.041), and low incidence rates of thrombocytopenia, abnormal liver and renal function. Children yielded better results in the duration of their hospital stay and the incidence of complications (P】

Background Aortic banding and debanding models have provided useful information on the development and regression of left ventricular hypertrophy (LVH). In this animal study, we aimed to evaluate left ventricular (LV) deformation related to the development and regression of LVH. Methods Minimally invasive ascending aorta banding was performed in rats (10 Sprague Dawley rats, 7 weeks). Ten rats underwent a sham operation. Thirty-five days later, the band was removed. Echocardiographic and histopathologic analysis was assessed at pre-banding, 35 days of banding and 14 days of debanding. Results Banding of the ascending aorta created an expected increase in the aortic velocity and gradient, which normalized with the debanding procedure. Pressure overload resulted in a robust hypertrophic response as assessed by gross and microscopic histology, transthoracic echocardiography [heart weight/tibia length (g/m); 21.0 ± 0.8 vs. 33.2 ± 2.0 vs. 26.6 ± 2.8, p < 0.001]. The circumferential (CS) and radial strains were not different between the groups. However, there were significant differences in the degree of fibrosis according to the banding status (fibrosis; 0.10 ± 0.20% vs. 5.26 ± 3.12% vs. 4.03 ± 3.93%, p = 0.003), and global CS showed a significant correlation with the degree of myocardial fibrosis in this animal model (r = 0.688, p = 0.028). Conclusion In this animal study, simulating a severe LV pressure overload state, a significant increase in the LV mass index did not result in a significant reduction in the LV mechanical parameters. The degree of LV fibrosis, which developed with pressure overload, was significantly related to the magnitude of left ventricular mechanics.

Purpose: Even though adipose tissue-derived stem cells (ADSCs) have been spotlighted as a possible alternative for liver transplantation in an experimental setting, the mechanism by which ADSCs improve liver dysfunction remains poorly characterized. The objective of this study was to evaluate the therapeutic ability of undifferentiated ADSCs, and find a few clues on how ADSCs alleviate liver damage by comparing the transplantation routes. Methods: In vitro generated human ADSCs were checked for surface markers and stage-specific genes for characterization. Afterwards, they were transplanted into C57BL/6 mice with CCl4-induced liver injury. The transplantations were made via tail vein, portal vein, and direct liver parenchymal injection. At 1 and 3 post-transplantation days, serum biochemical parameters and/or liver specimens were evaluated. Results: We have shown here that ADSCs have the characteristics of mesenchymal stem cells, and belong to endodermal and/or early hepatic differentiation stage. After transplantation into the mice with acute liver failure, markers of liver injury, such as alanineaminotransferase, aspartateaminotransferase, as well as ammonia, decreased. Of these transplantation routes, transplantation via tail vein rendered the most prominent reduction in the biochemical parameters. Conclusion: Undifferentiated ADSCs have the ability to improve hepatic function in mice with acute liver injury. Moreover, our transplantation route study supports the theory that ADSCs in systemic circulation can exert endocrine or paracrine effects to ameliorate the injured liver.