HBO1 induces histone acetylation and is important for non-small cell lung cancer cell growth.

We examined the expression and the potential biological function of HBO1 in non-small cell lung cancer (NSCLC). TCGA and Oncomine databases showed that HBO1 transcripts were elevated in NSCLC. Furthermore, in local NSCLC tumor tissues HBO1 expression was higher than that in matched adjacent lung tissues. In primary and immortalized NSCLC cells, HBO1 shRNA robustly inhibited cell viability, proliferation and migration. Moreover, HBO1 knockout by CRISPR/Cas9 induced significant anti-tumor activity in NSCLC cells. Conversely, ectopic HBO1 overexpression in primary NSCLC cells increased proliferation and migration. H3-H4 histone acetylation and expression of several potential oncogenic genes (CCR2, MYLK, VEGFR2 and OCIAD2) were significantly decreased in NSCLC cells with HBO1 silencing or knockout. They were however increased after HBO1 overexpression. Intratumoral injection of HBO1 shRNA-expressing adeno-associated virus hindered the growth of A549 cell xenografts and primary NSCLC cell xenografts in nude mice. H3-H4 histone acetylation as well as expression of HBO1 and HBO1-dependent genes were decreased in HBO1-silenced NSCLC xenograft tissues. An HBO1 inhibitor WM-3835 potently inhibited NSCLC cell growth. Together, HBO1 overexpression promotes NSCLC cell growth.

Arterial stiffness in adults with steady-state bronchiectasis: association with clinical indices and disease severity.

BACKGROUND: Cardiovascular disease are common co-morbidities in bronchiectasis and contribute substantially to disease burden and mortality. Brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness, has a strong predictive value for cardiovascular event. We hypothesized that baPWV would be increased in steady-state bronchiectasis patients, and correlates with the degree of systemic inflammation and disease severity assessed with Bronchiectasis Severity Index and FACED scores. METHODS: Eighty patients with steady-state bronchiectasis and 80 age- and sex-matched controls were enrolled. BaPWV was measured as an indicator of arterial stiffness. Demographic, clinical indices, radiology, spirometry, sputum bacteriology and systemic inflammatory mediators were also assessed. RESULTS: Bronchiectasis patients had significantly increased baPWV [median 1514 cm/s vs. 1352 cm/s, P = 0.0003] compared with control subjects. BaPWV significantly correlated with Bronchiectasis Severity Index (rho = 0.65, P < 0.001) and FACED (rho = 0.49, P < 0.001) scores. In multivariate regression analysis, age, Pseudomonas aeruginosa colonization, systolic blood pressure, body-mass index and exacerbation frequency in the last 12 months, but not systemic inflammatory markers, were independent factors influencing on baPWV in bronchiectasis patient after adjustment for other clinical variables. Reproducibility of baPWV measurement was good. CONCLUSION: Bronchiectasis patients have increased arterial stiffness compared with control subjects, which correlates with disease severity, but not systemic inflammatory markers. Age, Pseudomonas aeruginosa colonization, systolic blood pressure, body-mass index and exacerbation frequency in last 12 months might independently predict the severity of arterial stiffness in bronchiectasis. Therefore, arterial stiffness might have contributed to the increased risks of developing cardiovascular diseases in bronchiectasis.

Subclinical atherosclerosis in adults with steady-state bronchiectasis: A case-control study.

BACKGROUND AND OBJECTIVE: Bronchiectasis has been associated with increased risks of cardiovascular disease, in which early-stage endothelial dysfunction might have played pivotal roles. We aimed to investigate endothelial function in bronchiectasis patients, by measuring flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT) as compared with control subjects, and to elucidate the impact of different risk factors on subclinical atherosclerosis. METHODS: The study included 80 bronchiectasis patients and 80 age- and sex-matched healthy subjects. Vascular endothelial function was evaluated with FMD in the brachial artery in response to reactive hyperemia, and CIMT was measured with high-resolution ultrasonography. Disease severity was evaluated with Bronchiectasis Severity Index and FACED scores. Demographic, disease duration, radiology, spirometry, sputum bacteriology and systemic inflammatory indices were also assessed. RESULTS: FMD was significantly lower in bronchiectasis patients than in control subjects (8.92 ± 2.70% vs. 11.17 ± 3.44%, P < 0.001). FMD significantly correlated with Bronchiectasis Severity Index (rho = -0.60, P < 0.001) and FACED score (rho = -0.39, P < 0.001). In multivariate regression analysis, age, body-mass index, Pseudomonas aeruginosa colonization and high-resolution computed tomography scores were independent factors influencing on the FMD in bronchiectasis patients, even after adjustment for other clinical variables. No significant difference in CIMT was detected between bronchiectasis patients and healthy subjects (P > 0.05). CONCLUSIONS: Compared with healthy subjects, bronchiectasis patients have greater risks of endothelial dysfunction which is independent of previously well-studied risk factors, calling for the vigilance to screen early for vascular changes to minimize the future risks of cardiovascular events.

Subclinical atherosclerosis risk markers in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Identifying early changes of cardiovascular system before the occurrence of fatal clinical event is critical for the management of COPD. We performed a meta-analysis to investigate the associations between COPD and subclinical markers of cardiovascular risk. METHODS: We searched PUBMED, EMBASE for studies published before Aug 1st, 2016, on the association between COPD and carotid intima-media thickness (CIMT), prevalence of carotid plaques, flow-mediated dilation (FMD), pulse-wave velocity (PWV) and augmentation index (AIx). RESULTS: Thirty-two studies (3198 patients, 13867 controls) were included. Compared with controls, COPD patients had significantly higher CIMT (MD: 0.10 mm; 95% CI: 0.04, 0.16; p = 0.0007), PWV (SMD: 0.70; 95% CI: 0.52, 0.88; p < 0.0001), AIx (MD: 4.60%; 95% CI: 0.52, 8.68; p = 0.03), AIx@75 (AIx normalized to a heart rate of 75 beats per minute) (MD: 4.59%; 95% CI: 2.80, 6.38; p < 0.0001), prevalence of carotid plaque (OR: 2.54; 95% CI: 2.04, 3.15; p < 0.0001), and significantly lower FMD (MD: -4.21%; 95% CI: -6.71, -1.71; p = 0.001). Sensitivity and subgroups analyses substantially confirmed our results. Meta-regression analysis revealed that spirometry (as expressed by FEV1%predicted) might influence on PWV. CONCLUSIONS: These findings indicate that COPD, even in mild to moderate patients, had greater impaired markers of subclinical atherosclerosis and cardiovascular risk. However, further studies are still needed to address confounders, such as age, smoking, hypertension, diabetes etc, which might affect the associations in COPD patients.

Aetiology of bronchiectasis in adults: A systematic literature review.

While identifying the underlying aetiology is a key part of bronchiectasis management, the prevalence and impact of identifying the aetiologies on clinical management remain unclear. We aimed to determine the etiological spectrum of bronchiectasis, and how often etiological assessment could lead to the changes in patients' management. A comprehensive search was conducted using MEDLINE (via PubMed) and EMBASE for observational studies published before October 2015 reporting aetiologies in adults with bronchiectasis. Of the 8216 citations identified, 56 studies including 8608 adults with bronchiectasis were relevant for this systematic review. The crude prevalence for the identified aetiologies ranged from 18% to 95%, which possibly resulted from the differences in the geographic regions and diagnostic workup. Post-infective (29.9%), immunodeficiency (5%), chronic obstructive pulmonary disease (3.9%), connective tissue disease (3.8%), ciliary dysfunction (2.5%), allergic bronchopulmonary aspergillosis (2.6%) were the most common aetiologies. In 1577 patients (18.3%), identifying the aetiologies led to changes in patient's management. Aetiologies varied considerably among different geographic regions (P < 0.001). Intensive investigations of these aetiologies might help change patient's management and therefore should be incorporated into routine clinical practice.

[Effect of selenium-protein polysaccharide extracted from Se-rich Cordyceps militaris on tumor-bearing mice].

OBJECTIVE: To extract and analysis the active components of Se-protein polysaccharide from Se-rich Cordyceps militaris, and to discuss the anti-tumor effect of Se-protein polysaccharide. METHOD: Protein, polysaccharides and selenium content were determined by the methods of Folin-phenol reagent (lowry), phenol-sulfate and DAN fluorescence, respectively. Tumor-bearing mouse model was established and divided into the model group, cyclophosphamide group, cordyceps high and low dosage group (200, 100 mg x kg(-1)). Then the Se-protein polysaccharide's anti-tumor activity and immune function in vivo were observed by compare with model group in the weight of mice, inhibitory rate, conversion rate of peripheral blood lymphocytes, dissection index K, swallowed factor alpha, liver and spleen factor coefficient, GSH-Px and SOD activity and the content of MDA. RESULT: Se-protein polysaccharides from Se-rich Cordyceps militaris had a significant anti-tumor action with the inhibitory rate 46.92% and could avoid toxic effect of chemotherapy drug like cyclophosphamide. It also could enhance immune function and body antioxidant capacity by inhibiting the decline of tumor-bearing mouse liver coefficient and spleen coefficient in tumor-bearing mice caused by cyclophosphamide. CONCLUSION: Se-protein polysaccharide, the extraction of Se-rich Cordyceps militaris's can inhibit tumor grouth of tumor-bearing mouse.