Modulation of cigarette smoke extract-induced human bronchial epithelial damage by eucalyptol and curcumin.

Smoking is one of the most important leading death cause worldwide. From a toxicological perspective, cigarette smoke serves hazards especially for the human being exposed to passive smoke. Over the last decades, the effects of natural compounds on smoking-mediated respiratory diseases such as COPD, asthma, and lung cancer have been under investigation, as well as the mechanistic aspects of disease progression. In the present study, the protective mechanism of eucalyptol (EUC), curcumin (CUR), and their combination on BEAS-2B cells were investigated in vitro to understand their impact on cell death, oxidative cell injury, and inflammatory response induced by 3R4F reference cigarette extract (CSE). According to the present findings, EUC, CUR, and their combination improved cell viability, attenuated CSE-induced apoptosis, and LC3B expression. Further, CSE-induced oxidative damage and inflammatory response in human bronchial epithelial cells were remarkably reduced by the combination treatment through modification of enzymatic antioxidant activity, GSH, MDA, and intracellular ROS levels as well as nitrite and IL-6 levels. In addition, nuclear translocation of Nrf2, a regulatory protein involved in the indirect antioxidant response, was remarkably up-regulated with the combination pre-treatment. In conclusion, EUC and CUR in combination might be a potential therapeutic against smoking-induced lung diseases through antioxidant and inflammatory pathways and results represent valuable background for future in vivo pulmonary toxicity studies.

Steinernema innovationi n. sp. (Panagrolaimomorpha: Steinernematidae), a new entomopathogenic nematode species from South Africa.

Morphological and molecular sequence data were combined with cross-hybridization studies and used to identify a new Steinernema sp. from Free State, South Africa. Molecular and morphological data indicate that the new species belongs to the 'glaseri-group' of Steinernema spp. Key morphological diagnostic characters for S. innovationi n. sp. include the morphometric features of the third-stage infective juveniles: total body length = 1054 (1000-1103) µm, tail length = 108 (97-117) µm, location of the excretory pore = 88 (82-91) µm, and D% = 58 (54-63), E% = 115 (104-137) and H% = 43 (37-46). Additionally, the morphology of the spicules and gubernaculum of the first-generation males are considered key diagnostic traits. Steinernema innovationi n. sp. was also characterized by analysis of both rDNA and mitochondrial gene sequence data, which further indicate the uniqueness of this Steinernema species.

Impaired mitochondrial biogenesis contributes to depletion of functional mitochondria in chronic MPP+ toxicity: dual roles for ERK1/2.

The regulation of mitochondrial quality has emerged as a central issue in neurodegeneration, diabetes, and cancer. We utilized repeated low-dose applications of the complex I inhibitor 1-methyl-4-phenylpyridinium (MPP(+)) over 2 weeks to study cellular responses to chronic mitochondrial stress. Chronic MPP(+) triggered depletion of functional mitochondria resulting in diminished capacities for aerobic respiration. Inhibiting autophagy/mitophagy only partially restored mitochondrial content. In contrast, inhibiting activation of extracellular signal-regulated protein kinases conferred complete cytoprotection with full restoration of mitochondrial functional and morphological parameters, enhancing spare respiratory capacity in MPP(+) co-treated cells above that of control cells. Reversal of mitochondrial injury occurred when U0126 was added 1 week after MPP(+), implicating enhanced repair mechanisms. Chronic MPP(+) caused a >90% decrease in complex I subunits, along with decreases in complex III and IV subunits. Decreases in respiratory complex subunits were reversed by co-treatment with U0126, ERK1/2 RNAi or transfection of dominant-negative MEK1, but only partially restored by degradation inhibitors. Chronic MPP(+) also suppressed the de novo synthesis of mitochondrial DNA-encoded proteins, accompanied by decreased expression of the mitochondrial transcription factor TFAM. U0126 completely reversed each of these deficits in mitochondrial translation and protein expression. These data indicate a key, limiting role for mitochondrial biogenesis in determining the outcome of injuries associated with elevated mitophagy.

Turkish validation of the premature ejaculation diagnostic tool and its association with intravaginal ejaculatory latency time.

There are uncertain issues on the diagnostic methods of premature ejaculation (PE). The premature ejaculation diagnostic tool (PEDT) was developed to systematically apply the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria in diagnosing PE and the aim of this study is to carry out the Turkish validation of the PEDT and to evaluate its association with intravaginal ejaculatory latency time (IELT). A total of 94 patients with a self-reported complaint of PE and 88 men without PE were enrolled into the study and requested to complete the nine-item PEDT, which was translated into Turkish. The patients were also requested to measure IELT. All participants were requested to come for a second visit to assess the PEDT's retest reliability; data from 78 men in the PE group and 69 men in the control group were collected. The IELT data of 35 patients were also recorded. The mean age of the PE group and the control group were 39.4+/-9.7 (24-65) and 30.1+/-5.7 (20-56), respectively, (P=0.068). Among the patients in the PE group, 24 (68.5%) reported life-long PE, whereas 11 (31.5%) reported acquired PE. The geometric mean IELT of the PE group was 59.7+/-46.2 (6.5-197.7) s. The number of men reporting IELTs of <1, 1-<2 and >2 min were 20 (57.1%), 11 (31.5) and 4 (11.4%), respectively. The factor analysis assessment showed that the five-item combination (questions 1, 2, 3, 4 and 8) explained 74.4% of the variance, there were no other combinations that explained the variance more effectively. Cronbach's alpha score of five-item combination was calculated as 0.77, showing adequate internal consistency. The overall Cronbach's alpha score did not increase if any item combination was deleted. The test-retest correlation coefficients of each item were higher than 0.80 and the correlation coefficient of the total score was 0.90. The PEDT and IELT showed an adequate correlation (rho=0.44). As a conclusion, the validated five-item Turkish version of PEDT is a reliable questionnaire to screen PE among Turkish patients. Its significant association with IELT supports the fact that PEDT may be of benefit for the diagnosis of PE and measuring the response to treatment. In addition, PEDT seems to be more applicable than measuring IELT in our population, for the assessment of PE.