Irisin alleviates hyperoxia-induced bronchopulmonary dysplasia through activation of Nrf2/HO-1 pathway.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common pulmonary injury among premature infants, which is often caused by hyperoxia exposure. Irisin is a novel hormone-like myokine derived mainly from skeletal muscles as well as adipose tissues. Many studies have indicated that Irisin exert a variety of properties against hyperoxia-induced inflammation and oxidative stress (OS). We aimed to evaluate the effects of irisin on hyperoxia-induced lung injury explore the underlying mechanisms. METHODS: BPD model was established after exposing newborn mouse to 85% oxygen. BPD mouse received continuous intraperitoneal injection of irisin at a dose of 25 µg/kg/day. Lung tissues were collected for histological examination at 7 and 14 days after birth. The alveolarization and alveolar vascularization of each animal was assessed. Levels of oxidative stress indicators, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues were detected at 14 days after birth. RESULTS: Hyperoxia exposure induced a markedly alveolar simplification and a disrupted alveolar angiogenesis, which was ameliorated by irisin treatment. The hyperoxia-induced increase in these oxidative stress indicators was significantly reversed by irisin treatment. The Nrf2/HO-1 pathway is inducted in the hyperoxia-induced BPD mouse model, which is further activated by irisin treatment. CONCLUSION: Our results demonstrated the beneficial effects of irisin in reducing the OS, enhancing alveolarization, and promoting vascular development through activation of Nrf2/HO-1 axis in a hyperoxia-induced experimental model of BPD.

GRIK3 deficiency promotes non-small cell lung cancer progression by the regulation of the UBE2C/CDK1/Wnt signaling pathway.

Glutamate ionotropic receptor kainate type subunit 3 (GRIK3) is a predominant excitatory neurotransmitter receptor in the mammalian brain. While it is known that GRIK3 is involved in normal neurophysiologic processes, its biological functions in tumor progression are still poorly understood due to limited investigation. In this study, we reported for the first time that GRIK3 expression was downregulated in non-small cell lung cancer (NSCLC) tissues as compared to paracarcinoma tissues. Additionally, we observed that GRIK3 expression was strongly correlated with the prognosis of NSCLC patients. We also noted that GRIK3 suppressed the cell proliferation and migration capability of NSCLC cells, thereby inhibiting xenografts growth and metastasis. Mechanistically, GRIK3 deficiency increased the expression of ubiquitin-conjugating enzyme E2 C (UBE2C) and cyclin-dependent kinase 1 (CDK1), which resulted in the activation of the Wnt signaling pathway and enhanced NSCLC progression. Our findings suggest that GRIK3 plays a role in regulating NSCLC progression and that its expression may serve as an independent prognostic indicator for NSCLC patients.

Elevated endocan concentration is associated with coronary slow flow.

We sought to assess whether serum endocan concentration is correlated with coronary slow flow (CSF). We measured serum endocan concentration in 93 patients with CSF and in 206 controls. Serum endocan concentration was measured by enzyme-linked immunosorbent assay (ELISA). The presence of CSF was assessed by thrombolysis in myocardial infarction (TIMI) frame count (TFC) method. We demonstrated that serum endocan concentration is significantly higher in CSF patients (n = 93) than that in controls (n = 206) (1.03 [range 0.63-1.33] vs. 0.80 [range 0.52-1.09] ng/mL, p = 0.002). Multivariate logistic regression analysis revealed that serum endocan concentration was independently associated with the presence of CSF (odds ratio 1.774, 95% confidence interval 1.064-2.958; p = 0.028). Serum endocan concentration was positively correlated with mean-TFC in CSF patients (r = 0.289, p = 0.005). These results revealed that endocan might be a useful biomarker for predicting the presence and severity of CSF. Therapeutic interventions by down-regulating endocan to delay the progressive process of CSF warrants further investigations.

Elevated Human Endothelial Cell-Specific Molecule-1 Level and Its Association With Coronary Artery Disease in Patients With Hypertension.

BACKGROUND: Endothelial dysfunction plays an important role in the pathophysiology of coronary artery disease (CAD). Previous studies suggested that human endothelial cell-specific molecule-1 (endocan) may be a novel endothelial dysfunction marker. This study aims to investigate the relationship between serum endocan level and the presence and severity of CAD in patients with hypertension. METHODS: A total of 190 eligible hypertension patients were enrolled in this study. Serum endocan level was measured by enzyme-linked immunosorbent assay. The presence and severity of CAD were evaluated by coronary angiography. RESULTS: Hypertensive patients with CAD had significantly higher serum endocan level than those without CAD (1.63 ± 0.51 ng/mL vs 1.31 ± 0.65 ng/mL, P < 0.05). Multivariate logistic regression revealed that serum endocan level was independently associated with the presence of CAD (odds ratio, 2.662; 95% confidence interval, 1.560-4.544; P < 0.001). Spearman rank correlation analysis demonstrated that serum endocan level was associated with SYNergy between PCI with TAXUS and Cardiac Surgery score (r = 0.349, P = 0.001). CONCLUSIONS: Serum endocan level is independently correlated with the presence and severity of CAD in hypertension patients, and those with high endocan level may have an increased risk of developing atherosclerosis.

Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China.

BACKGROUND: The clonal spread of Acinetobacter baumannii is a global problem, and carbapenems, such as imipenem, remain the first-choice agent against A. baumannii. Using synergy to enhance the antibiotic activity of carbapenems could be useful. Here, amlodipine (AML) was tested alone and with imipenem against A. baumannii isolates. METHODS: Forty-two isolates of A. baumannii were collected. Multilocus sequence typing (MLST) assessed the genetic relationship of the isolates. The resistance phenotypes were determined using disc diffusion. The minimum inhibitory concentrations (MICs) of the drugs were determined by broth microdilution. The combined effects of the drugs were determined by a checkerboard procedure. Metallo-ß-lactamase (MBL) was determined using the MBL Etest. RESULTS: Forty-two A. baumannii isolates were collected from 42 patients who were mostly older than 65 years and had long inpatient stays (≥ 7 days). A. baumannii was mostly recovered from the respiratory system (N = 35, 83.3%). Most patients (N = 27, 64.3%) received care in intensive care units (ICUs). Disc diffusion testing demonstrated that A. baumannii susceptibility to polymyxin B was 100%, while susceptibility to other antimicrobial agents was less than 30%, classifying the isolates into 10 MDR and 32 XDR strains. MLST grouped the A. baumannii isolates into 4 existing STs and 6 new STs. STn4 carried allele G1, with a T → C mutation at nt3 on the gpi111 locus. STn5 carried allele A1, possessing A → C mutations at nt156 and nt159 on the gltA1 locus. ST195 and ST208 accounted for 68.05% (29/42) of the isolates. Clonal relation analysis showed that ST195 and ST208 belonged to clonal complex (CC) 92. The inhibitory concentration of imipenem ranged from 0.5 to 32 µg/ml, and that of AML ranged from 40 to 320 µg/ml. In combination, the susceptibility rate of A. baumannii isolates increased from 16.7% to 54.8% (P = 0.001). In the checkerboard procedure, half of the isolates (N = 21, 50.0%) demonstrated synergy or partial synergy with the drug combination. The MBL Etest revealed that 1 A. baumannii strain (N = 1, 2.4%) produced MBL. CONCLUSIONS: CC92 was the major clone spreading in our hospital. AML improved the activity of imipenem against A. baumannii isolates in vitro but did not inhibit MBL.

Atherosclerotic plaque identification by virtual histology intravascular ultrasound in a rabbit abdominal aorta model of vulnerable plaque.

This study aimed to evaluate the utility of virtual histology intravascular ultrasound (VH-IVUS) for recognizing vulnerable plaque compared to histological pathological analysis. Four-month-old New Zealand rabbits (n = 16) were randomly divided into two groups: one fed a high-fat diet and subjected to balloon injury (experimental, n = 10) and one fed a high-fat diet alone (control, n = 6). Blood lipid profiles of overnight-fasted rabbits were measured at week 2 (beginning of study) and week 12 (end of study). At week 12, experimental group rabbits underwent IVUS under anaesthesia. Rabbits were sacrificed and a 5-cm segment of the abdominal aorta was removed. Arterial sections were subjected to pathological and immunohistochemical analyses. Serum lipid levels increased in all rabbits fed with high-fat diet, with low-density lipid cholesterol (LDL-C) levels increasing the most. Levels of six biomarkers (high sensitivity C-reactive protein, matrix metalloproteinase-3, interleukin [IL]-1, IL-10, tumour necrosis factor-α, and oxidized [ox]-LDL) showed no differences between the two groups at week 2, but were higher in the experimental group at week 12. A total of 276 atherosclerotic plaques in the experimental group were analysed. VH-IVUS had sensitivities of 87% and 92% for detection of noncalcified and calcified thin-cap fibroatheromas, respectively. VH-IVUS correctly identified 85% and 89% of noncalcified and calcified fibroatheromas, respectively. For detection of pathological intimal thickening, VH-IVUS showed a sensitivity of 79% and positive predictive value of 78%. Linear regression analysis showed a strong correlation between histology and VH-IVUS for the percent area of fibrous fibro-fatty tissue, necrotic calcified tissue, and confluent necrotic core. The intra-observer and inter-observer variability of the intimal and medial-adventitial boundaries was low. Endothelial injury followed by a high-fat diet in rabbits is a viable method for inducing atheroma, and VH-IVUS is a feasible, reproducible, and valuable means of vulnerable plaque identification in vivo.

The effect of physician's 30 s smoking cessation intervention for male medical outpatients: a pilot randomized controlled trial.

OBJECTIVE: To study the effectiveness of a very brief advice (<30 s) on smoking cessation. DESIGN: A 'proof-of-principle' single-blind, randomized controlled trial (RCT). SETTING: Medical outpatient clinics of a general hospital in Guangzhou, China. PARTICIPANTS: One hundred and twenty-six male current smokers randomly allocated into an intervention (n = 74) and a control group (n = 52). Intervention A health warning by physicians that half of all smokers would be killed by smoking, an advice to quit immediately and referral to a cessation clinic. The control group received none. OUTCOMES: Primary: seven-day quitting point prevalence at 6 months. Secondary: 7-day point prevalence at 1, 3 and 12 months, sustained abstinence at 3, 6 and 12 months, smoking reduction by half and cessation clinic attendance. RESULTS: By intention-to-treat analysis, 7-day quitting point prevalence rates at four follow-ups were 27.0, 23.0, 21.6 and 18.9% in the intervention group, compared with 5.8, 3.8, 5.8 and 5.8% in the control group (first three P < 0.05). At 3, 6 and 12 months, sustained abstinence prevalence rates were 18.9, 17.6 and 14.9% versus 3.8, 3.8 and 3.8% (P = 0.035, 0.046, 0.074). More smokers in the intervention group had reduced smoking. Almost no participants attended the cessation clinic. CONCLUSION: Our findings support the need for large RCTs on minimal interventions with the 'one in two' warning.

Mutations in the N-terminal Transcriptional Activation Region of Androgen Receptor in the Chinese.

Activation function (AF1) region of N-terminal domain of androgen receptor (AR) is necessary for the transcriptional activation function of AR. The sequences of AF1 in twenty normal chinese were amplified by PCR and determined by direct dsDNA cycle sequencing. Based on this, the mutations in AF1 of AR in patients with androgen insensitivity syndrome(AIS) or prostate cancer(PC) were screened by a combination of single strand conformation polymorphism(SSCP) analysis and direct dsDNA cycle sequencing. The sequences between normal chinese and other races were identical and one point mutation (C966A, Ser296Arg), which had not been reported so far, was identified in a patient with prostate cancer with poor differentiation. That suggests alteration of structure and function in AF1 of N-terminal domain of AR might be relative with PC progression of some patients.