Intravenous N-acetylcysteine in respiratory disease with abnormal mucus secretion.

OBJECTIVE: Evidence for the mucolytic and expectorant efficacy of intravenous (IV) N-acetylcysteine (NAC) is limited. This study aimed to evaluate in a large, multicenter, randomized, controlled, subject, and rater-blinded study whether IV NAC is superior to placebo and non-inferior to ambroxol in improving sputum viscosity and expectoration difficulty. PATIENTS AND METHODS: A total of 333 hospitalized subjects from 28 centers in China with respiratory disease (such as acute bronchitis, chronic bronchitis and exacerbations, emphysema, mucoviscidosis, and bronchiectasis) and abnormal mucus secretion were randomly allocated in a 1:1:1 ratio to receive NAC 600 mg, ambroxol hydrochloride 30 mg, or placebo as an IV infusion twice daily for 7 days. Mucolytic and expectorant efficacy was assessed by ordinal categorical 4-point scales and analyzed by stratified and modified Mann-Whitney U statistics. RESULTS: NAC showed consistent and statistically significant superiority to placebo and non-inferiority to ambroxol in change from baseline to day 7 in both sputum viscosity scores [mean (SD) difference 0.24 (0.763), p<0.001 vs. placebo] and expectoration difficulty score [mean (SD) difference 0.29 (0.783), p=0.002 vs. placebo]. Safety findings confirm the good tolerability profile of IV NAC reported from previous small studies, and no new safety concerns were identified. CONCLUSIONS: This is the first large, robust study of the efficacy of IV NAC in respiratory diseases with abnormal mucus secretion. It provides new evidence for IV NAC administration in this indication in clinical situations where the IV route is preferred.

MicroRNA-145 inhibits proliferation and promotes apoptosis of HepG2 cells by targeting ROCK1 through the ROCK1/NF-κB signaling pathway.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a malignant cancer with a high fatality rate, and the expression of microRNA-145 (miR-145) is significantly low in HCC tissue. Therefore, the effect of miR-145 on HCC was explored. PATIENTS AND METHODS: Primary hepatocellular carcinoma samples and corresponding normal samples, and HepG2 cells were analyzed using flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Real-time quantitative reverse transcription-polymerase chain reaction, Western blotting, and dual-luciferase reporter assay. RESULTS: miR-145 expression was significantly downregulated in HCC tissue and HepG2 cells as compared to normal liver tissue. After HepG2 cells were transfected with miR-145 mimics, miR-145 expression was recovered, accompanied by a significantly lower cell number, inhibition of the G1/S phase transition, and promotion of the apoptosis of HepG2 cells, as well as changes in levels of G1/S-specific cyclin-E1 (CCNE1) and activated caspase-3. Furthermore, the rho-associated protein kinase 1 (ROCK1) levels were opposite the levels of miR-145 expression in vivo and in vitro, and additional experiments with co-transfection of miR-145 mimics and pEGFP-N3-3'UTR provided the direct evidence that the ROCK1 gene is a target of miR-145. Moreover, a significant decrease or increase in the expression of ROCK1 was associated with nuclear factor-kB (NF-κB)(p65) activity, and lipopolysaccharide (LPS) significantly increased NF-κB(p65) activity, accompanied by recovery of the reduction in the number of HepG2 cells for miR-145 mimics. The NF-κB activity and cell number were significantly (p < 0.05, p < 0.01) increased in response to the overexpression of the ROCK1 gene in HepG2 cells. CONCLUSIONS: We showed that miR-145 can target and downregulate ROCK1 expression, and it controls HCC by inhibiting the cell cycle and activating apoptosis via the ROCK1/NF-κB signaling pathway. Our findings will provide a new perspective for the therapy of HCC.

HMGB1 affects the development of pulmonary arterial hypertension via RAGE.

OBJECTIVE: To investigate the effect of high-mobility group box 1 (HMGB1) on the proliferation, migration and inflammatory response of human pulmonary artery smooth muscle cells (HPASMCs) and human pulmonary artery endothelial cells (HPAECs) through the receptor for advanced glycation end products (RAGE) and to investigate the mechanism of action underlying the effect of HMGB1 on pulmonary arterial hypertension. MATERIALS AND METHODS: The effect of HMGB1 on the proliferation of the two cell types was examined using the MTT assay under environmental hypoxia (incubation with 1.5% oxygen) to simulate the condition of pulmonary arterial hypertension in the body. The effect of HMGB1 on HPAEC migration was observed using the scratch assay. The effect of HMGB1 on the inflammatory mediators IL-6 and CXCL8 in the two cell types was assessed using qPCR (Real-time Quantitative PCR) and ELISA, and the RAGE mRNA and protein expression levels were also examined. RESULTS: Hypoxia promoted the proliferation of both cell types but inhibited the migration of HPAECs. HMGB1 had no obvious effect on the proliferation and migration of the cells. Both hypoxia and HMGB1 promoted the expression of the pro-inflammatory factors IL-6 and CXCL8. HMGB1 significantly promoted RAGE expression compared to the normal control group. CONCLUSIONS: HMGB1 affects the functions of HPASMCs and HPAECs through RAGE and may affect the course of pulmonary arterial hypertension.

The anesthetic agent sevoflurane attenuates pulmonary acute lung injury by modulating apoptotic pathways

The objective of this study was to evaluate lung protection by the volatile anesthetic sevoflurane (SEVO), which inhibits apoptosis. Male Sprague-Dawley rats (250–280 g; n=18) were randomly divided into three groups. The LPS group received 5 mg/kg endotoxin (lipopolysaccharide), which induced acute lung injury (ALI). The control (CTRL) group received normal saline and the SEVO group received sevoflurane (2.5%) for 30 min after ALI was induced by 5 mg/kg LPS. Samples were collected for analysis 12 h after LPS. Lung injury was assessed by pathological observations and tissue wet to dry weight (W/D) ratios. Apoptotic index (AI) was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and electron microscopy. Caspase-3 and cleaved-caspase-3 protein levels were determined by immunocytochemistry and western blotting, respectively. Bcl-xl levels were measured by western blotting and Bcl-2 levels by quantitative real-time polymerase chain reaction and western blotting. In the LPS group, W/D ratios, AI values, caspase-3 and cleaved-caspase-3 levels were significantly higher than in the CTRL group and lung injury was more severe. In the SEVO group, W/D ratios, AI, caspase-3 and cleaved-caspase-3 were lower than in the LPS group. Bcl-2 and Bcl-xl expression were higher than in the LPS group and lung injury was attenuated. Sevoflurane inhalation protected the lungs from injury by regulating caspase-3 activation and Bcl-xl and Bcl-2 expression to inhibit excessive cell apoptosis, and such apoptosis might be important in the pathogenesis of LPS-induced ALI.

Long noncoding RNA PVT1 as a novel serum biomarker for detection of cervical cancer.

OBJECTIVE: To investigate long noncoding RNA PVT1 expression in the serum of cervical cancer patients, and to evaluate serum PVT1 level as a diagnostic biomarker for cervical cancer. PATIENTS AND METHODS: Eighty-eight cervical cancer patients, 64 cervical intraepithelial neoplasia patients, 25 breast cancer patients, 25 ovarian cancer patients, and 111 healthy control subjects were enrolled into this study. PVT1 serum level in these participants and PVT1 expression in 20 pairs of cervical cancer tissues and adjacent paired normal tissues was measured by quantitative reverse transcription-polymerase chain reaction. The diagnostic values of serum PVT1 were evaluated by receiver operating characteristic curves analysis. RESULTS: Serum PVT1 level is significantly increased in cervical cancer patients and correlated with tumor size, clinical stage, and lymph node metastasis of cervical cancer. Serum PVT1 could accurately discriminate cervical cancer patients from cervical intraepithelial neoplasia patients and healthy control subjects, and also discriminate early stage cervical cancer patients from healthy control subjects. But serum PVT1 level is not changed in breast cancer and ovarian cancer patients. Furthermore, serum PVT1 level is positively correlated with tissue PVT1 expression, and could indicate cervical cancer dynamics. CONCLUSIONS: Long noncoding RNA PVT1 may be a novel noninvasive biomarker for early diagnosis of cervical cancer.

Aggressive fibromatosis of the larynx: case report and brief review.

Aggressive fibromatosis is a rare, benign, fibroblastic neoplasm, characterized by local invasion and a relatively high rate of recurrence. Here a case of laryngeal aggressive fibromatosis in a 47-year old man is reported. The patient presented with worsening dyspnoea and hoarseness and was hospitalized for treatment with partial laryngectomy. Final pathological evaluation of the tumour confirmed a diagnosis of aggressive fibromatosis. The patient has remained disease-free without further treatment for 5 years. This study demonstrated that aggressive fibromatosis may occur around the larynx and can be managed by partial laryngectomy alone. It is, therefore, important to include this rare disease entity in the routine differential diagnosis of laryngeal masses.