Antioxidant effect of lactic acid bacteria in human bronchial epithelial cells exposed to cigarette smoke.

AIMS: Chronic lung diseases are a major and increasing global health problem, commonly caused by cigarette smoke. We aimed to explore the antioxidant effects of lactic acid bacteria (LAB) against cigarette smoke in bronchial epithelial cells. METHODS AND RESULTS: The antioxidant effects of 21 heat-killed (HK) LAB strains were tested in cigarette smoke-stimulated BEAS-2B cells and 3-D bronchospheres organoids. We showed that HK Lactiplantibacillus plantarum BGPKM22 possesses antioxidant activity against cigarette smoke, resistance to hydrogen peroxide, and free radical neutralizing activity. We demonstrated that HK BGPKM22 inhibited cigarette smoke-induced expression of the Aryl hydrocarbon receptor (AhR) and Nuclear factor erythroid 2 related factor 2 (Nrf2) genes. The cell-free supernatant (SN) of BGPKM22 fully confirmed the effects of HK BGPKM22. CONCLUSIONS: For the first time, we revealed that HK and SN of Lactip. plantarum BGPKM22 possess antioxidant activity and modulate AhR and Nrf2 gene expression in bronchial epithelial cells exposed to cigarette smoke.

Stathmin is enriched in the developing corticospinal tract.

Understanding the intra- and extracellular proteins involved in the development of the corticospinal tract (CST) may offer insights into how the pathway could be regenerated following traumatic spinal cord injury. Currently, however, little is known about the proteome of the developing corticospinal system. The present study, therefore, has used quantitative proteomics and bioinformatics to detail the protein profile of the rat CST during its formation in the spinal cord. This analysis identified increased expression of 65 proteins during the early ingrowth of corticospinal axons into the spinal cord, and 36 proteins at the period of heightened CST growth. A majority of these proteins were involved in cellular assembly and organization, with annotations being most highly associated with cytoskeletal organization, microtubule dynamics, neurite outgrowth, and the formation, polymerization and quantity of microtubules. In addition, 22 proteins were more highly expressed within the developing CST in comparison to other developing white matter tracts of the spinal cord of age-matched animals. Of these differentially expressed proteins, only one, stathmin 1 (a protein known to be involved in microtubule dynamics), was both highly enriched in the developing CST and relatively sparse in other developing descending and ascending spinal tracts. Immunohistochemical analyses of the developing rat spinal cord and fetal human brain stem confirmed the enriched pattern of stathmin expression along the developing CST, and in vitro growth assays of rat corticospinal neurons showed a reduced length of neurite processes in response to pharmacological perturbation of stathmin activity. Combined, these findings suggest that stathmin activity may modulate axonal growth during development of the corticospinal projection, and reinforces the notion that microtubule dynamics could play an important role in the generation and regeneration of the CST.

Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease.

Alzheimer disease (AD) is a complex neurodegenerative disorder, whose prevalence will dramatically rise by 2050. Despite numerous clinical trials investigating this disease, there is still no effective treatment. Many trials showed negative or inconclusive results, possibly because they recruited only patients with severe disease, who had not undergone disease-modifying therapies in preclinical stages of AD before severe degeneration occurred. Detection of AD in asymptomatic at risk individuals (and a few presymptomatic individuals who carry an autosomal dominant monogenic AD mutation) remains impractical in many of clinical situations and is possible only with reliable biomarkers. In addition to early diagnosis of AD, biomarkers should serve for monitoring disease progression and response to therapy. To date, the most promising biomarkers are cerebrospinal fluid (CSF) and neuroimaging biomarkers. Core CSF biomarkers (amyloid ß1-42, total tau, and phosphorylated tau) showed a high diagnostic accuracy but were still unreliable for preclinical detection of AD. Hence, there is an urgent need for detection and validation of novel CSF biomarkers that would enable early diagnosis of AD in asymptomatic individuals. This article reviews recent research advances on biomarkers for AD, focusing mainly on the CSF biomarkers. In addition to core CSF biomarkers, the potential usefulness of novel CSF biomarkers is discussed.

Comparison of two commercial enzyme-linked immunosorbent assays for cerebrospinal fluid measurement of amyloid ß1-42 and total tau.

Amyloid ß1-42 (Aß1-42), total tau (t-tau), and phosphorylated tau (p-tau) are the main cerebrospinal fluid (CSF) biomarkers for early diagnosis of Alzheimer's disease (AD). Detection of AD is critically important in view of the growing number of potential new drugs that may influence the course of the disease in its early phases. However, cut-off levels for these CSF biomarkers have not yet been established. Variability in absolute concentrations of AD biomarkers is high among studies and significant differences were noticed even within the same datasets. Variability in biomarkers levels in these assays may be due to many aspects of operating procedures. Standardization of pre-analytical and analytical procedures in collection, treatment, and storage of CSF samples is crucial because differences in sample handling can drastically influence results. Multicenter studies showed that usage of ELISA kits from different manufacturers also affects outcome. So far only very few studies tested the efficiency of ELISA kits produced by different vendors. In this study, the performance of Innogenetics (Gent, Belgium) and Invitrogen (Camarillo, CA, USA) ELISA kits for t-tau and Aß1-42 was tested. Passing-Bablok analysis showed significant differences between Invitrogen and Innogenetics ELISA methods, making it impossible to use them interchangeably.

Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking.

Nicotine addiction, related to cigarette smoking, develops as a product of the complex interactions between social, environmental and genetic factors. Genes encoding the components of the dopaminergic system are thought to be associated with smoking. Literature data showed not only an association, but also a lack of association between variable number of tandem repeats (VNTR) polymorphism located in the third exon of dopamine D4 receptor (DRD4) gene and smoking. Repetitive sequence of DRD4 VNTR is 48 bp long and maximum 11 tandem copies were reported in humans. Presence of alleles with 6 and more repeats (i.e. long alleles) was associated with greater tendency to novelty seeking and addictive behaviors than the presence of 5 and less alleles (short alleles). The aim of this study was to determine the association between VNTR in DRD4 gene and present smoking status in ethnically homogenous Caucasian population from the Eastern European (Croatian) origin. Genotyping was done in 565 healthy subjects, 511 men and 54 women, respectively, who were subdivided into 176 smokers and 389 nonsmokers. Logistic regression analyses, adjusted for age and sex, revealed the lack of significant (p>0.05) effect of the 4/4, 4/7 and 7/7 genotypes, or carriers of the long and short allele, or all genotypes of the DRD4 VNTR on smoking status. The results of this study failed to confirm the hypothesis that long allele of the DRD4 VNTR is associated with smoking status in Caucasian subjects.