Circ-ITCH restrains the expression of MMP-2, MMP-9 and TNF-α in diabetic retinopathy by inhibiting miR-22.

Diabetic retinopathy (DR), the most frequent complication of diabetes mellitus, is the principal cause of acquired blindness worldwide. Although the roles of circRNAs have been extensively explored, the detailed physiological and pathological functions of circRNAs in DR are less understood. Here, we studied the biological effects of circ-ITCH in diabetic retinal pigment epithelial cells (RPEs) and explored the underlying mechanisms. As our results shown, the RNA expression of circ-ITCH was significantly lower in RPEs isolated from diabetic rats than they were in those isolated from normal rats. While diabetes induced an increase in MMP-2, MMP-9 and TNF-α in RPEs, circ-ITCH overexpression exerted an inhibitory on these increases and knockdown of circ-ITCH reversed the inhibitory. In addition, increased expression of miR-22 in RPEs correlated with diabetes and downregulation of circ-ITCH. Remarkably, in the presence of miR-22 mimics, the effects of circ-ITCH on the MMP-2 and MMP-9 were both antagonized. Collectively, our data supports a cellular signaling cascade in which circ-ITCH-inhibited miR-22 activity modulates the expression of MMP-2, MMP-9 and TNF-α in DR.

Low-intensity walking as mild medication for pressure control in prehypertensive and hypertensive subjects: how far shall we wander?

Successful prevention and treatment of hypertension depend on the appropriate combination of antihypertensive drug therapy and nondrug lifestyle modification. While most hypertension guidelines recommend moderate- to high-intensity exercise, we decided to explore a mild yet effective type of exercise to add to hypertension management, especially in populations with complications or frailty. After comparing the short-term cardiovascular effects of low-speed walking versus high-speed walking for 3 kilometers (km) (3 km/h versus 6 km/h) in young, healthy volunteers, we delivered low-speed walking (low-intensity walking, 2.5 metabolic equivalents of task, METs) as exercise therapy in 42 prehypertensive and 43 hypertensive subjects. We found that one session of 3 km low-intensity walking exerted a transient pressure-lowering effect as well as a mild negative chronotropic effect on heart rate in both the prehypertensive and hypertensive subjects; these short-term benefits on blood pressure and heart rate were accompanied by a brief increase in urine ß-endorphin output. Then we prescribed regular low-intensity walking with a target exercise dose (exercise volume) of 500-1000 METs·min/week (50-60 min/day and 5-7 times/week) in hypertensive subjects in addition to their daily activities. Regular low-intensity walking also showed mild but significant blood pressure-lowering and heart rate-reducing effects in 7 hypertensive subjects within two months. It is hypothesized that regular low-intensity exercise of the necessary dose could be taken as a pragmatic and supplementary medication for hypertension management.

p53 and mitochondrial dysfunction: novel insight of neurodegenerative diseases.

Mitochondria are organelles responsible for vital cell functions. p53 is a transcription factor that regulates the DNA stability and cell growth normality. Recent studies revealed that p53 can influence mitochondrial function changing from normal condition to abnormal condition under different stress levels. In normal state, p53 can maintain mitochondrial respiration through transactivation of SCO2. When stress stimuli presents, SCO2 overexpresses and leads to ROS generation. ROS promotes p53 inducing MALM (Mieap-induced accumulation of lysosome-like organelles within mitochondria) to repair dysfunctional mitochondria and MIV (Mieap-induced vacuole) to accomplish damaged mitochondria degradation. If stress or damage is irreversible, p53 will translocate to mitochondria, leading into apoptosis or necrosis. Neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease are still lack of clear explanations of mechanisms, but more studies have revealed the functional relationship between mitochondria and p53 towards the pathological development of these diseases. In this review, we discuss that p53 plays the vital role in the function of mitochondria in the aspect of pathological change metabolism. We also analyze these diseases with novel targeted treating molecules which are related to p53 and mitochondria, hoping to present novel therapies in future clinic.

Nitric Oxide Mediates Inflammation in Type II Diabetes Mellitus through the PPARγ/eNOS Signaling Pathway.

Inflammation accounts for the process of type II diabetes mellitus (T2DM), the specific mechanism of which is still to be elucidated yet. Nitric oxide (NO), a critical inflammation regulator, the role of which is the inflammation of T2DM, is rarely reported. Therefore, our study is aimed at exploring the effect of NO on the inflammation in T2DM and the corresponding mechanism. We analyzed the NO levels in plasma samples from T2DM patients and paired healthy adults by Nitric Oxide Analyzer then measured the expression of inflammatory cytokines (C-reactive protein, heptoglobin, IL-1ß, TNF-α, IL-6) in insulin-induced HepG2 cells treated with NO donor or NO scavenger, and the PPARγ, eNOS, C-reactive protein, heptoglobin, IL-1ß, TNF-α, and IL-6 levels were detected by RT-PCR and western blot in insulin-induced HepG2 cells transfected with si-PPARγ. The results showed that excess NO increased the inflammation marker levels in T2DM, which is activated by the PPARγ/eNOS pathway. These findings will strengthen the understanding of NO in T2DM and provide a new target for the treatment of T2DM.

Wide Angle of Incidence-Insensitive Polarization-Independent THz Metamaterial Absorber for Both TE and TM Mode Based on Plasmon Hybridizations.

An ultra-wide-angle THz metamaterial absorber (MA) utilizing sixteen-circular-sector (SCR) resonator for both transverse electric (TE) and transverse magnetic (TM) mode is designed and investigated numerically. At normal incidence, the absorptivity of the proposed MA is higher than 93.7% at 9.05 THz for different polarization angles, due to the rotational symmetry structure of the unit cell. Under oblique incidence, the absorptivity can still exceed 90%, even when the incident angle is up to 70° for both TE and TM mode. Especially, the frequency variation in TE mode is less than 0.25% for different incident angles from 0° to 70°. The electric field (Ez) distributions are used to explain the absorption mechanism. Numerical simulation results show that the high absorption with wide-angle independence stems from fundamental dipole resonance and gap surface plasmons. The broadband deep-infrared MA is also obtained by stacking three metal-dielectric layers. The designed MA has great potential in bolometric pixel elements, biomedical sensors, THz imaging, and solar cells.

Lentiviral Vectors and Adeno-Associated Virus Vectors: Useful Tools for Gene Transfer in Pain Research.

Pain, especially chronic pain, has always been a heated point in both basic and clinical researches since it puts heavy burdens on both individuals and the whole society. A better understanding of the role of biological molecules and various ionic channels involved in pain can shed light on the mechanism under pain and advocate the development of pain management. Using viral vectors to transfer specific genes at targeted sites is a promising method for both research and clinical applications. Lentiviral vectors and adeno-associated virus (AAV) vectors which allow stable and long-term expression of transgene in non-dividing cells are widely applied in pain research. In this review, we thoroughly outline the structure, category, advantages and disadvantages and the delivery methods of lentiviral and AAV vectors. The methods through which lentiviral and AAV vectors are delivered to targeted sites are closely related with the sites, level and period of transgene expression. Focus is placed on the various delivery methods applied to deliver vectors to spinal cord and dorsal root ganglion both of which play important roles in primary nociception. Our goal is to provide insight into the features of these two viral vectors and which administration approach can be chosen for different pain researches. Anat Rec, 301:825-836, 2018. © 2017 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Acute hepatitis A infection in children: a 20-year experience of a medical center in Southern Taiwan.

BACKGROUND: Taiwan is currently nonendemic for hepatitis A infection, but sporadic cases are reported occasionally. The presenting symptoms of acute hepatitis A (AHA) infection in children are often nonspecific and may be easily misdiagnosed as general gastrointestinal illness. METHODS: We conducted this study to identify the relevant presenting symptoms and laboratory findings of AHA in children. The medical records of all patients younger than 18 years old admitted to Kaohsiung Chang Gang Memorial Hospital from July 1986 to June 2004 under the diagnosis of AHA were reviewed. There were 29 pediatric patients admitted with the diagnosis of AHA, including 16 male patients and 13 female patients. RESULTS: Poor appetite, malaise, abdominal pain, vomiting and fever were the leading constitutional symptoms. Jaundice and tea-colored urine were the most relevant hepatobiliary presentations. Elevation of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct and indirect bilirubin was common, although other hematology and biochemistry examinations were within normal limits on most occasions. There was no mortality in our series. A slightly increasing prevalence of AHA was noted over the two decades of the study period, although it was not statistically significant. CONCLUSIONS: Our results found that children with AHA tended to present with non-specific gastrointestinal symptoms and acute liver function deterioration. Elevation of hepatic aminotransferase and alkaline phosphatase with cholestasis was common.

Gamma-glutamyl transferase in the diagnosis of biliary atresia.

BACKGROUND: Early diagnosis of biliary atresia (BA) is important because the prognosis is closely related to timing of Kasai operation. The aim of this study was to test the clinical application of serum gamma-glutamyl transferase (GGT) concentration and the ratio of serum GGT to aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in differentiating BA from neonatal hepatitis (NH). METHODS: Ninety-three (46 male and 47 female) cases of BA and 65 (45 male and 20 female) NH were included in this study. Serum concentrations of GGT, AST, and ALT were measured in all cholestatic infants. The results of peak GGT level, GGT/AST ratio, GGT/ALT ratio were compared between groups. RESULTS: The serum GGT levels were significantly higher in BA patients than those in NH patients (353.3 +/- 334.4 IU/L vs. 114.8 +/- 86 IU/L, P < 0.001). GGT/AST values were over 2 in 55/68 BA and 15/ 54 NH (OR = 11.0, 95% CI 4.7-25.7, P < 0.001). GGT/ALT values were over 2 in 54/65 BA and 19/50, NH respectively (OR = 8.0, 95% CI 3.4-19.0, P < 0.001). A GGT level greater than 300 IU/L had a sensitivity of 39.7% in the diagnosis of BA, GGT/AST over 2 was 80.9% and GGT/ALT over 2 was 83.1%; the specificities were 98.1%, 72.2% and 62.0%, respectively. The respective accuracies of the diagnosis of BA were 65.6%, 77.1% and 73.9%. CONCLUSIONS: GGT/AST ratio over 2 indicates high possibility of biliary atresia and should prompt further investigations to confirm the diagnosis.

[Analysis on the injury by lock-against-theft].

Nowdays, it is common seen that criminals tend to use the lock-against-theft for motorcycle to harm others as a tool. In order to find out the chief characters of this kind of injury, 28 cases in which victims were hurt by lock-against-theft for motorcycle were analyzed. In each case, the victims carefully questioned to confirm the damage procedure. Furthermore, the wound configuration was observed and the forming mechanism was deduced to provide morphological evidences for the judgement in this kind of case.

Endovascular stent-graft repair of aortic dissection.

Between October 2000 and January 2002, 9 consecutive male patients with subacute or chronic aortic dissection underwent stent-graft placement. The indication for surgery was continuous pain or aneurysm development. One patient had a type A dissecting aortic aneurysm with a primary tear in the ascending thoracic aorta; the other 8 had type B dissection. Placement of an endovascular stent-graft was technically successful in 8 patients, and one underwent an open procedure for abdominal aortic fenestration. The entry site was sealed and the false lumen disappeared in 8 cases, and thrombosis of the false lumen was obtained. Rupture of an iliac artery dissecting aneurysm occurred in one patient 2 days after stent-graft placement; abdominal aortic fenestration with prosthetic replacement of the distal abdominal aorta was performed. One patient died of myocardial infarction 3 days after the stent-graft procedure. During a mean follow-up period of 7 months (1-16 months), one patient died of acute myocardial infarction at 11 months. It was concluded on the basis of these short-term results that endovascular repair of aortic dissection is a promising treatment, and abdominal aortic fenestration is a useful adjuvant procedure.

Clinical significance of erythromycin-resistant Campylobacter jejuni in children.

Campylobacter has been recognized as the common cause of bacterial gastroenteritis in many countries. Increasing erythromycin resistance in Campylobacter jejuni infection is noted recently, but severe case was rarely reported. In this study, we aimed to clarify the clinical significance of the resistant strain of C jejuni in children. We reviewed the charts of children who were diagnosed with C jejuni enteritis in our hospital from January 2000 to December 2005, including 326 patients (117 males and 209 females). All the cases had positive stool culture. We divided them into two groups, the sensitive group (a total of 306 cases) and resistant group (a total of 20 cases), according to the drug sensitivity. We analyzed the clinical manifestations and laboratory data between the two groups. The mean age was 3.79 ± 3.24 years in the sensitive group and 3.03 ± 2.84 years in the resistant group. There was no significant difference between the two groups in clinical presentations and laboratory examinations. No mortality was found, and one case was initially presented with colonic perforation. This report demonstrates that infection by erythromycin-resistant strains of C jejuni has no clinical significance in children, despite the probably increased emergence of erythromycin resistance.

In vitro shear stress modulates antithrombogenic potentials of human endothelial progenitor cells.

BACKGROUND: Recent study suggested that endothelial progenitor cells (EPCs), a novel therapeutic approach for endothelial dysfunction, present limited antithrombogenic potentials. However, few attempts have been done to improve the antithrombogenic potentials of EPCs. Our previous study proved that in vitro shear stress contributes to the increase in t-PA production by human EPCs. Here, we further investigated whether in vitro shear stress contributes to the secretion of antithrombogenic substances including plasminogen activator inhibitor-1 (PAI-1) and prostaglandin I(2) (PGI(2)) by human EPCs. METHODS: The peripheral blood mononuclear cells of healthy subjects were induced into EPCs. Then the human EPCs were treated with four levels of shear stress including stationary condition low media and high flow shear stress. The production of PAI-1 and 6-keto-prostaglandin F1(1alpha)(6-Keto-PGF(1alpha)) by human EPCs with shear stress treatment were measured. RESULTS: In vitro medium and high flow shear stress inhibited PAI-1 secretion by human EPCs, but low flow shear stress had no effect on PAI-1 secretion by human EPCs. All levels of shear stress significantly increased 6-Keto-PGF(1alpha )production by human EPCs in a dose-dependent manner. CONCLUSIONS: The present study demonstrates that in vitro shear stress can promote PGI(2 )secretion and inhibit PAI-1 secretion by human EPCs, which improves the antithrombogenic potentials of human EPCs.

Facial Candida albicans cellulitis occurring in a patient with oral submucous fibrosis and unknown diabetes mellitus after local corticosteroid injection treatment.

Facial cellulitis caused by odontogenic bacterial infection is frequently encountered; however, facial cellulitis caused by Candida albicans infection is rarely found. A patient with oral submucous fibrosis (OSF) and unknown diabetes mellitus (DM) was treated in our out-patient dental clinic by biweekly submucosal injection of 40 mg triamcinolone acetonide into bilateral buccal mucosae plus forced mouth opening performed by the two hands of the clinician. The interincisal distance of the patient improved from 28 to 48 mm after four times of steroid injection. The symptoms and signs of OSF also improved markedly. Unfortunately, facial candidal cellulitis occurred 2 months after the last time of steroid injection treatment. The infection was cured by incision and drainage, intravenous administration of amphotericin B (100 mg once a day for a week), and an appropriate medical control of DM. No recurrence of facial cellulitis was found during the follow-up period of 18 months. To prevent the occurrence of facial cellulitis after a high-dose steroid therapy, some prophylactic procedures should be taken before the initiation of the steroid treatment.