Transforming activities of Chlamydia pneumoniae in human mesothelial cells

Knowledge in viral oncology has made considerable progress in the field of cancer fight. However, the role of bacteria as mediators of oncogenesis has not yet been elucidated. As cancer still is the leading cause of death in developed countries, understanding the long-term effects of bacteria has become of great importance as a possible means of cancer prevention. This study reports that Chlamydia pneumoniae infection induce transformation of human mesothelial cells. Mes1 cells infected with C. pneumoniae at a multiplicity of infection of 4 inclusion-forming units/cell showed many intracellular inclusion bodies. After a 7-day infection an increased proliferative activity was also observed. Real-time PCR analysis revealed a strong induction of calretinin, Wilms’ tumour gene 1, osteopontin, matrix metalloproteinases-2, and  membrane-type 1 metalloproteinases gene expression in Mes1 cell, infected for a longer period (14 days). The results were confirmed by western blot analysis. Zymography analysis showed that C. pneumoniae modulated the in-vitro secretion of MMP-2 in Mes1 cells both at 7 and 14 days. Cell invasion, as measured by matrigel-coated filter, increased after 7 and 14 days infection with C. pneumoniae, compared with uninfected Mes1 cells. The results of this study suggest that C. pneumoniae infection might support cellular transformation, thus increasing lung cancer risk. [Int Microbiol 2014; 17(4):185-193]Keywords: Chlamydia pneumoniae · cytotoxicity · human mesothelial cells · cellular transformation · tumoral marker

Occurence and Bioactivities of Funicone-Related Compounds

Studies on production of secondary metabolites by fungi have received a substantial boost lately, particularly with reference to applications of their biological properties in human medicine. Funicones represent a series of related compounds for which there is accumulating evidence supporting their possible use as pharmaceuticals. This paper provides a review on the current status of knowledge on these fungal extrolites, with special reference to aspects concerning their molecular structures and biological activities

Textile industry manufacturing by-products induce human melanoma cell proliferation via ERK1/2 activation

OBJECTIVES: Textiles used to make clothing can represent a source, often ignored, of chemicals potentially noxious to both skin and the whole organism. Among the most frequently produced potentially noxious chemical manufacturing by-products are formaldehyde (FA), nickel (Ni) and hexavalent chromium (Cr); they are of potential clinical interest as all are known to be carcinogenic to humans and to be potent skin sensitizers. The aim of this study was to investigate, in vitro, effects of these potentially dangerous compounds on two different melanoma cell lines. In particular, attention was focused on A375P, a poorly metastatic and low invasive cell line and SK-MEL-28, a highly metastatic cell line. MATERIALS AND METHODS: Effects of these compounds was evaluated on A375P and SK-MEL-28 cells. FA (1-5 7 10(-5) m), NiSO4 (10(-6) -10(-3) m), K2 Cr2 O7 (10(-7) -10(-6) m) effects on cell proliferation were evaluated by cell counting, while ERK pathway involvement was evaluated by Western blot analysis. RESULTS: Low concentrations of the chemicals, covering a range that corresponds to commonly accepted limits in textile production, induced a significant increase in cell proliferation concomitant with transient activation of phosphorylated ERK expression. CONCLUSIONS: Data obtained suggest that increasing attention must be focused on these by-products' potentially harmful effects in chemical manufacturing of clothes and accessories, that remain for long periods of time, in contact with human skin

First evidence of an altered microbiota and intestinal damage and its link to absence epilepsy in a genetic animal model, the WAG/Rij rat

Objective: A large number of studies have highlighted the important role of the gut microbiota in the pathophysiology of neurological disorders, suggesting that its manipulation might serve as a treatment strategy. We hypothesized that the gut microbiota participates in absence seizure development and maintenance in the WAG/Rij rat model and tested this hypothesis by evaluating potential gut microbiota and intestinal alterations in the model, as well as measuring the impact of microbiota manipulation using fecal microbiota transplantation (FMT). Methods: Initially, gut microbiota composition and intestinal histology of WAG/Rij rats (a well-recognized genetic model of absence epilepsy) were studied at 1, 4, and 8 months of age in comparison to nonepileptic Wistar rats. Subsequently, in a second set of experiments, at 6 months of age, untreated Wistar or WAG/Rij rats treated with ethosuximide (ETH) were used as gut microbiota donors for FMT in WAG/Rij rats, and electroencephalographic (EEG) recordings were obtained over 4 weeks. At the end of FMT, stool and gut samples were collected, absence seizures were measured on EEG recordings, and microbiota analysis and histopathological examinations were performed. Results: Gut microbiota analysis showed differences in beta diversity and specific phylotypes at all ages considered and significant variances in the Bacteroidetes/Firmicutes ratio between Wistar and WAG/Rij rats. FMT, from both Wistar and ETH-treated WAG/Rij donors to WAG/Rij rats, significantly decreased the number and duration of seizures. Histological results indicated that WAG/Rij rats were characterized by intestinal villi disruption and inflammatory infiltrates already at 1 month of age, before seizure occurrence; FMT partially restored intestinal morphology while also significantly modifying gut microbiota and concomitantly reducing absence seizures. Significance: Our results demonstrate for the first time that the gut microbiota is modified and contributes to seizure occurrence in a genetic animal model of absence epilepsy and that its manipulation may be a suitable therapeutic target for absence seizure management

Gut Microbiota Features in Young Children With Autism Spectrum Disorders

Proliferation and/or depletion of clusters of specific bacteria regulate intestinal functions and may interfere with neuro-immune communication and behavior in patients with autism spectrum disorder (ASD). Consistently, qualitative and quantitative alteration of bacterial metabolites may functionally affect ASD pathophysiology. Up to date, age-restricted cohort studies, that may potentially help to identify specific microbial signatures in ASD, are lacking. We investigated the gut microbiota (GM) structure and fecal short chain fatty acids (SCFAs) levels in a cohort of young children (2–4 years of age) with ASD, with respect to age-matched neurotypical healthy controls. Strong increase of Bacteroidetes and Proteobacteria and decrease of Actinobacteria was observed in these patients. Among the 91 OTUs whose relative abundance was altered in ASD patients, we observed a striking depletion of Bifidobacterium longum, one of the dominant bacteria in infant GM and, conversely, an increase of Faecalibacterium prausnitzii, a late colonizer of healthy human gut and a major butyrate producer. High levels of F. prausnitzii were associated to increase of fecal butyrate levels within normal range, and over representation of KEGG functions related to butyrate production in ASD patients. Here we report unbalance of GM structure with a shift in colonization by gut beneficial bacterial species in ASD patients as off early childhood

Corrigendum: Gut Microbiota Features in Young Children With Autism Spectrum Disorders

[This corrects the article DOI: 10.3389/fmicb.2018.03146.]

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

Osteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease (IBD). The aim of our study was to analyze the association of osteopontin (OPN/SPP1) gene variants in a large cohort of IBD patients. Genomic DNA from 2819 Caucasian individuals (n = 841 patients with Crohn's disease (CD), n = 473 patients with ulcerative colitis (UC), and n = 1505 healthy unrelated controls) was analyzed for nine OPN SNPs (rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138). Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs (rs4754, rs1126616, rs1126772 and rs9138), we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients (p = 0.0004, OR = 0.69). None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 (omnibus p-value = 2.07×10⁻⁸). Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10⁻⁵). There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 (p = 4.18×10⁻²) and between OPN SNP rs1126616 and IL23R SNP rs2201841 (p = 4.18×10⁻²) but none of these associations remained significant after Bonferroni correction. Our study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans