Computational Analysis of miR-140 and miR-135as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy

Background@#Degenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expression and regulation of tendon injury and healing, we attempted to evaluate the combinatorial effect of selected miRNAs for better healing of degenerative tendinopathy. @*Methods@#The present study was designed to evaluate the combinatorial effect of two miRNAs (has-miR-140 and has-miR-135) in the healing process of the tendon. Publicly available information/data were retrieved from appropriate platforms such as PubMed.Only molecular data, directly associated with tendinopathies, including genes/proteins and miRNAs, were used in this study. The miRNAs involved in tendinopathy were analyzed by a Bioinformatics tools (e.g., TargetScan, miRDB, and the RNA22v2). Interactive involvement of the miRNAs with key proteins involved in tendinopathy was predicted by the Insilco approach. @*Results@#Based on information available in the public domain, tendon healing-associated miRNAs were predicted to explore their therapeutic potentials. Based on computation analysis, focusing on the potential regulatory effect on tendon healing, the miR-135 and miR-140 were selected for this study. These miRNAs were found as key players in tendon healing through Rho-associated coiled-coil containing protein kinase 1 (ROCK1), IGF-1/PI3K/Akt, PIN, and Wnt signaling pathways. It was also predicted that these miRNAs may reprogram the cells to induce proliferation and differentiation activity. Many miRNAs are likely to regulate genes important for the tendinopathy healing process, and the result of this study allows an approach for miRNA-mediated regeneration of the tenocyte for tendon healing. Based on computational analysis, the role of these miRNAs in different pathways was established, and the results provided insights into the combinatorial approach of miRNA-mediated cell reprogramming. @*Conclusions@#In this study, the association between miRNAs and the disease was evaluated to correlate the tendinopathy genes and the relevant role of different miRNAs in their regulation. Through this study, it was established that the synergistic effect of more than one miRNA on directed reprogramming of the cell could be helpful in the regeneration of damaged tissue. It is anticipated that this study will be helpful for the design of miRNA cocktails for the orchestration of cellular reprogramming events.

A Case of Sweet's Syndrome in a Patient with Liver Cirrhosis Caused by Chronic Hepatitis B / 대한소화기학회지

Sweet's syndrome (SS), also known as acute febrile neutrophilic dermatosis, is characterized by the sudden onset of painful erythematous skin lesions together with fever and neutrophilia. SS can be associated with several disorders, such as malignancy, autoimmune disease, and infections. However, SS associated with liver cirrhosis is uncommon. We report a case of SS in a patient who was diagnosed with liver cirrhosis caused by chronic hepatitis B.

Apoptosis-related mRNA expression profiles of ovarian cancer cell lines following cisplatin treatment / 부인종양

OBJECTIVE: The aim of this study was to identify apoptosis-related genes of ovarian cancer cell lines following cisplatin treatment. METHODS: We used IC50 values and fluorescence-activated cell sorting analysis to compare cell death in 2 ovarian cancer cell lines, namely, SKOV-3 and OVCAR-3, upon treatment with cisplatin. Moreover, the change in transcriptional levels of apoptosis-associated genes was measured with a dendron-modified DNA microarray. RESULTS: The protein levels for the up-regulated genes in each cell line were validated to identify the molecules that may determine the cellular behavior of cisplatin resistance. Eight genes were over-expressed in the 2 cell lines. The cisplatin-induced up-regulation of DAD1 in transcriptional and protein levels contributed to the cisplatin resistance of OVCAR-3, and the up-regulation of FASTK and TNFRSF11A in SKOV-3 resulted in its higher sensitivity to cisplatin than that of OVCAR-3. CONCLUSION: In the present study, we have identified a set of genes responsible for apoptosis following cisplatin treatment in ovarian cancer cell lines. These genes may give information about the understanding of cisplatin-induced apoptosis in ovarian cancer.

Acute Effects of Caffeine on Arterial Stiffness in Young Healthy Subjects

BACKGROUND AND OBJECTIVES: Coffee is one of the most popular beverages in the world. Caffeine is one of the substances contained in coffee and it is well known to increase blood pressure and the peripheral vascular resistance, in part because it stimulates the sympathetic nervous system. Arterial stiffness is an important factor for the performance of the cardiovascular system and it is an independent prognosticator of cardiovascular disease. We investigated the acute effect of caffeine on arterial stiffness in young healthy subjects. SUBJECTS AND METHODS: We enrolled 20 young healthy subjects, who were randomly divided two groups. The caffeine group (10 subjects, 4 males, mean age: 23.3+/-1.1 years) received 520 mL caffeinated coffee and the control group (10 subjects, 4 males, mean age: 23.1+/-1.3 years) received 520 mL water. The arterial stiffness was evaluated by the carotid-radial pulse wave velocity and the augmentation index as corrected by heart rate (75 bpm), and all the hemodynamic measurements were obtained at baseline, 30, 60, 120 and 180 minutes after ingestion of the coffee or water. RESULTS: Arterial stiffness measured by carotid-radial pulse wave velocity increased progressively from 9.4+/-1.2 m/sec at baseline to 11.5+/-1.6 m/sec (p<0.05) at 30 minutes after the coffee intake. In addition, peripheral systolic pressure increased progressively from 107.1+/-10.2 mmHg at baseline to 114.4+/-12.9 mmHg (p<0.05) at 60 minutes after the coffee intake. Such changes were not seen in control group. CONCLUSION: Caffeine affects increased the pulse wave velocity and systolic blood pressure. This means that coffee might have an adverse effect on arterial stiffness.

Pseudo-Kaposi's Sarcoma Developing After Surgery on a Lower Limb Fracture / 대한피부과학회지

Pseudo-Kaposi's sarcoma is a reactive vasoproliferating disorder that resembles Kaposi's sarcoma. In most cases, it has been associated, with venous insufficiency and congenital or iatrogenic arteriovenous fistula. We report a 56-year-old female patient with pseudo-Kaposi's sarcoma, probably caused by chronic lymphedema and venous insufficiency, which developed after open reduction and internal fixation for right femoral fracture.

A case of huge thrombi in right atrium for taking bed rest after percutaneous coronary intervention / 대한내과학회지

After percutaneous coronary intervention through femoral artery, patient must take a bed rest for a long time. Immobility is a risk factor that increase venous thromboembolism. We report 74-years old female who experienced with huge thrombi in right atrium after taking a bed rest, which was related with percutaneous coronary intervention.

Characteristics of the Doppler Myocardial Imaging in Patients with Myocardial Hypertrophy

BACKGROUND: Myocardial Doppler imaging has allowed the quantification of regional myocardial motion. The aim of this study was to characterize regional left ventricular systolic and diastolic function by myocardial Doppler imaging (velocity and deformation) in patients with normal, concentric hypertrophy due to hypertension and hypertrophic cardiomyopathy (HCM). METHOD: In forty-five patients (normal 15, concentric hypertrophy 15, HCM 15), we assessed the time velocity integral (systolic, early and late diastolic), systolic strain and strain rate (SR) (systolic, early and late diastolic) at apical 4 chamber view (basal septum, mid-septum, apical setum, apex, apico-lateral, mid-lateral, and basal lateral wall). RESULT: The mean interventricular septal dimensions of normal, concentric hypertrophy and HCM were 0.96 cm, 1.31 cm and 1.73 cm, respectively (p<001). Patients with HCM reduced peak systolic strain, systolic SR, early diastolic SR and late diastolic SR at mid-septum (-0.58%, -0.92/sec, 0.37/sec, 1.06/sec, respectively) compared with that in normal and concentric hypertrophy (-20.27%, -1.71/sec, 1.58/sec, 1.94/sec, p<0.01and -14.37%, -1.01/sec, 1.31/sec, 1.73/ sec, p<0.01). In the patients with HCM, peak systolic strain in mid-septum (-0.58%) was significantly less than that in the basal, and apical septum and apical, mid, and basal lateral wall (-14.21%, -18.47%, -8.81%, -9.00%, -8.58%, respectively, p<0.05). In the concentric hypertrophy group, the average peak systolic strain of septal and lateral wall (-16.88%, -5.82%) were reduced compared with that in normal group (-2119%, -14.40%, respectively, p<0.05). The interventricular septal dimension was significant correlation between mid-septal systolic strain, systolic SR, early diastolic SR, and late diastolic SR (r=0.707 p<0.01, r=0689 p< 0.01, r=-0.687 p<0.01, r=-0.554 p<0.01) in all 45 patients. CONCLUSION: Hypertrophied myocardium had abnormality of myocardium deformation related to the degree of hypertrophy. Myocardial Doppler imaging offer a approach to quantify regional systolic and diastolic dysfunction.

The Characteristics of Unipolar and Bipolar Electrograms at the Origin of Ventricular Tachycardia

BACKGROUND AND OBJECTIVES: In radiofrequency catheter ablation (RFCA), it is an essential point to understand the characteristics of local electrograms at arrhythmic focus. However controversy exists as whether the unipolar or bipolar electrogram is superior in detecting arrhythmic focus. SUBJECTS AND METHODS: We evaluated the characteristics of unipolar and bipolar electrograms at ventricular tachycardia (VT) origin. Electroanatomical mapping and RFCA were performed in 6 patients with idiopathic VT. 22 sites were enrolled and 6 of them were successful sites. We analyzed the relationship between surface and local electrograms in accordance with success or failure. We also analyzed the morphology of local electrograms. RESULTS: At successful sites of RFCA, point of unipolar onset (22.86+/-10.82 msec vs 5.47+/-26.31 msec, p<0.05) and maximal negative slope (16.57+/-17.46 msec vs -4.00+/-22.77 msec, p<0.05) were recorded earlier than unsuccessful sites. R wave amplitude (0.11+/-0.19 mm vs 0.64+/-0.57 mm, p<0.05) and R/S ratio (0.02+/-0.30 vs 0.18+/-0.26, p<0.05) of unipolar electrograms were smaller at successful sites. R wave duration was shorter at successful sites (6.29+/-8.49 msec vs 11.33+/-6.26 msec) but there was no statistical significance. QRS duration of bipolar electrograms was longer at successful sites (66.14+/-17.93 msec vs 49.07+/-13.11 msec, p<0.05). CONCLUSION: In electranatomical mapping for VT, point of unipolar onset and maximal negative slope could predict local activation time more precisely Unipolar electrograms showed shorter R wave duration and smaller R/S ratio at successful sites of RFCA. We can estimate the focus of VT by using these chracteristics of unipolar and bipolar electrogram.

The Relationship between Progression of Coronary Artery Stenosis and Serum Adiponectin, ICAM(Intercellular Adhesion Molecule)-1 Level

BACKGROUND AND OBJECTIVE: Adiponectin is an adipocyte derived plasma protein that is known to have an anti-atherogenic effect. Low plasma adiponectin concentrations are found in obesity, diabetes and coronary artery disease. The measurement of the plasma adiponectin level is helpful in the assessment of the risk for coronary artery disease. The intercellular adhesion molecule (ICAM)-1 is associated with the atherosclerotic inflammatory response. An elevated ICAM-1 concentration is associated with increased risk of future coronary events, independent of other risk factors. The relationships between serum adiponectin and ICAM-1 levels and the progression of coronary artery stenosis with instent restenosis of previous stent sites were analyzed. SUCJECTS AND METHODS: 83 patients who had percutaneous transluminal coronary angioplasty and stent insertion were enrolled. The initial angiographic finding was compared with that at the 6 month follow up. The serum adiponectin and ICAM-1 level were measured with the plasma lipid profiles prior to percutaneous coronary intervention. These biochemical parameters were analyzed according to the progression of coronary artery stenosis (> or =10%) and instent restenosis (> or =50%). RESULTS: In the coronary artery stenosis progression group, there were significantly lower adiponectin (3.91+/-1.24 microgram/mL vs. 4.66+/-1.36 microgram/mL, p=0.03) and higher ICAM-1 levels (199.16+/-79.13 ng/mL vs. 150.54+/-63.65 ng/mL, p=0.03). The instent restenosis group also showed lower adiponectin (3.99+/-1.22 microgram/mL vs. 4.33+/-1.38 microgram/mL) and higher ICAM-1 (195.17+/-68.45 ng/mL vs. 171.47+/-80.48 ng/mL) levels, but without statistical significance. CONCLUSION: The serum adiponectin and ICAM-1 levels are related to the progression of coronary artery stenosis. However, further study will be required to confirm the relationships between the serum adiponectin and ICAM-1 levels and instent restenosis.

The bone changes of the midpalatal suture after rapid palatal expansion in young adult dogs / 대한치과교정학회지

Rapid palatal expansion(RPE) is a method of inducing the new bone formation in the palate by separation of the midpalatal suture, which can be done conveniently by placing heavy force across the maxillary dental arch. This experiment was undertaken to examine the histologic changes after RPE and during retention period. Four young adult dogs(a control dog, three experimental dogs) aged 4 to 6 months old were used for this experiment Expansion screw(Hyrax(R), Dentarum Inc.) was delevered to the palate and turned 180 degrees every morning and evening for 8 days, giving a total expansion of 72mm. A control dog was sacrified at the starting point of this study without any treatment and three experimental dogs were sacrified after RPE, 14-day retention, and 28-day retention in each. Thereafter, those samples were observed with hematoxylin-eosin(H-E) stain, ground section(Vrillanueva stain), alkaline phosphatase(ALP) stain, tartrate-resistant acid phosphatase(TRA) stain. The results were as followings: 1. After RPE, collagen fiber bundles were stretched along the midpalatal suture and few osteoblasts were flattenedinactive state and also, a little osteoid tissues was observed. Few multinucleated osteoclasts which had TRAPpositive activity in their cytoplasm were seen in horizontal section, whereas a few osteoclasts were seen in frontal section, especially in the nasal floor side of palatal bone. 2. After 14-day retention, collagen fiber bundles were stretched along the midpalatal suture and few osteoblasts which had ALP-positive activity in their cytoplasm were seen. Few multinucleated osteoclasts which had TRAP-positive activity in their cytoplasm were seen in horizontal section, whereas a few osteoclasts were seen in frontal section, especially in the nasal floor side of palatal bone. 3. After 28-day retention, collagen fiber bundles were arranged like those of control dog and osteoblasts which showed a lot of immature bone formation were cuboidal shape and exhibited ALP-positive activity in their cytoplasm. Few multinucleated osteoclasts which had TRAP-positive activity in their cytoplasm were seen in horizontal section, whereas a few osteoclasts were seen in frontal section, especially in the nasal floor side of palatal bone. According to the above results, the new bone formation after rapid palatal expansion was examined after 14-day retention and significantly increased. after 28-day retention.