Brominated flame-retardant (BFRs) exposure promotes multiple adverse health outcomes involved in oxidative stress, inflammation, and tissues damage. We investigated BFR effects, known as polybrominated diphenyl ethers (PBDEs) (47, 99 and 209) in an air-liquid-interface (ALI) airway tissue derived from A549 cell line, and compared with ALI culture of primary human bronchial epithelial cells (pHBEC). The cells, exposed to PBDEs (47, 99 and 209) (0.01-1 μM) for 24 h, were studied for IL-8, Muc5AC and Muc5B (mRNAs and proteins) production, as well as NOX-4 (mRNA) expression. Furthermore, we evaluated tight junction (TJ) integrity by Trans-Epithelial Electrical Resistance (TEER) measurements, and zonula occludens-1 (ZO-1) expression in the cells, and pH variations and rheological properties (elastic G', and viscous G″, moduli) in apical washes of ALI cultures. N-acetylcysteine (NAC) (10 mM) effects were tested in our experimental model of A549 cells. PBDEs (47, 99 and 209) exposure decreased TEER, ZO-1 and pH values, and increased IL-8, Muc5AC, Muc5B (mRNAs and proteins), NOX-4 (mRNA), and rheological parameters (G', G″) in ALI cultures of A549 cell line and pHBEC. NAC inhibited PBDE effects in A549 cells. PBDE inhalation might impairs human health of the lungs inducing oxidative stress, inflammatory response, loss of barrier integrity, unchecked mucus production, as well as altered physicochemical and biological properties of the fluids in airway epithelium. The treatment with anti-oxidants restored the negative effects of PBDEs in epithelial cells.

Concomitant heart failure is associated with poor clinical outcome in dialysis patients. The arteriovenous shunt, created as vascular access for hemodialysis, increases ventricular volume-overload, predisposing patients to developing cardiac dysfunction. The integral function of mitochondrial respiration is critically important for the heart to cope with hemodynamic overload. The involvement, however, of mitochondrial activity or reactive oxygen species (ROS) in the pathogenesis of ventricular-overload-induced heart failure has not been fully elucidated. We herein report that disorganization of mitochondrial respiration increases mitochondrial ROS production in the volume-overloaded heart, leading to ventricular dysfunction. We adopted the murine arteriovenous fistula (AVF) model, which replicates the cardinal features of volume-overload-induced ventricular dysfunction. Enzymatic assays of cardiac mitochondria revealed that the activities of citrate synthase and NADH-quinone reductase (complex Ⅰ) were preserved in the AVF heart. In contrast, the activity of NADH oxidase supercomplex was significantly compromised, resulting in elevated ROS production. Importantly, the antioxidant N-acetylcysteine prevented the development of ventricular dilatation and cardiac dysfunction, suggesting a pathogenic role for ROS in dialysis-related cardiomyopathy. A cardioprotective effect was also observed in metformin-treated mice, illuminating its potential use in the management of heart failure complicating diabetic patients on dialysis.

Nickel (Ni) is a silver-white transition metal that is widely used in the production field due to its unique physical and chemical properties. As a toxicant, long-term exposure to Ni can cause rhinitis, pneumonia and other respiratory inflammation. In the present study, we investigated the effect of particles extracted from Ni-refining fumes on cell viability, inflammation-related proteins and mitochondrial damage in human lung epithelial Beas-2B cells. The cells were exposed to Ni-refining fume particles for 24 h at concentrations of 0, 6.25, 12.50 and 25.00 μg/mL. The expression levels of the NACHT-LRR-PYD domains-containing protein 3 (NLRP3), caspase-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β and tumor necrosis factor (TNF)-α protein in Beas-2B cells exposed to Ni-refining fume particles increased significantly. Downregulation of NLRP3 expression by siRNA decreased the content of IL-1β. During activation of NLRP3, the mitochondrial membrane potential (MMP) decreased, the opening rate of mitochondrial permeability transition pore (MPTP) increased, and the content of reactive oxygen species (ROS) increased. Using lipopolysaccharide (LPS) intervention as the positive control group, N-acetylcysteine (NAC, an effective ROS remover) acted as an inhibitor. After NAC reduced the level of ROS, activation of the NLRP3 inflammasome was significantly inhibited. Ni-refining fumes caused significant cytotoxicity, inflammation and mitochondrial damage in Beas-2B cells. The present study thus provides experimental support for the hypothesis that Ni-refining fumes cause inflammation by inducing ROS production in Beas-2B cells.

Clinical efficacy of acetylcysteine combined with tetrandrine tablets in the treatment of silicosis and the effect on serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients with silicosis was investigated. One hundred and ninety-six patients with silicosis admitted to Qingdao Central Hospital, aged 40 to 70 years, were collected by prospective analysis. The patients were divided into two groups according to the different methods of treatment. The 108 patients in the control group received routine treatment, including anti-inflammatory, cough and asthma relief and 88 patients in the observation group were treated with tetrandrine combined with N-acetylcysteine on the basis of routine treatment. The curative effect of the two groups was analyzed by X-ray, and the incidence of adverse reactions was compared between the two groups. There was no significant difference in the effective rate between the two groups (P>0.05). After treatment, respiratory rate (RR) decreased, and forced vital capacity (FVC), and first second forced expiratory volume (FEV1) increased in both groups (P<0.05). RR in the observation group was lower than that in the control group (P<0.05), FVC and FEV1 were higher than those in the control group (P<0.05). There was no significant difference in serum IL-6 and TNF-α levels between the two groups before treatment (P>0.05). After treatment, the levels of IL-6 and TNF-α in the two groups decreased (P<0.05), and the IL-6 and TNF-α levels in the observation group after treatment were significantly lower than those in the control group (P<0.05). According to the effect of clinical treatment, the patients were re-divided into two groups. In conclusion, tetrandrine combined with acetylcysteine can effectively improve the clinical therapeutic effect of silicosis and alleviate the degree of inflammatory reaction in patients with silicosis. The levels of IL-6 and TNF-α in peripheral blood are valuable for the clinical treatment of silicosis.

A previous algorithm for the pharmacological treatment of obsessive-compulsive disorder was published in 2012. Developments over the past 7 years suggest an update is needed. The authors conducted searches in PubMed, focusing on new studies and reviews since 2012 that would support or change previous recommendations. We identified exceptions to the main algorithm, including pregnant women and women of child-bearing potential, the elderly, and patients with common medical and psychiatric co-morbidities. Selective serotonin reuptake inhibitors (SSRIs) are still first-line. An adequate trial requires a period at typical antidepressant doses and dose adjustments guided by a plasma level to evaluate for poor adherence or ultra-rapid metabolism. If the response is inadequate, consider a trial of another SSRI this time possibly taken to a very high dose. Clomipramine could be an alternative. If the response to the second trial remains inadequate, the next recommendation is to augment with aripiprazole or risperidone. Alternatively, augmentation with novel agents could be selected, including glutamatergic (memantine, riluzole, topiramate, n-acetylcysteine, lamotrigine), serotonergic (ondansetron), and anti-inflammatory (minocycline, celecoxib) agents. A third option could be transcranial magnetic stimulation. Lastly, after several of these trials, deep brain stimulation and cingulotomy have evidence for a role in the most treatment-refractory patients.