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Hidradenitis suppurativa (HS) is a pathology characterized by chronic inflammation and skin lesions. The molecular basis of the inflammatory network remains unclear; however, since microRNAs (miRNAs) are involved in the modulation of inflammation, the composition of a micro-transcriptome RNA library using the blood of HS patients was analysed here. The total miRNA expression profiles of miRNAs from HS patients was assayed by real-time qPCR. Here, compared to healthy controls, miR-24-1-5p, miR-146a-5p, miR26a-5p, miR-206, miR338-3p, and miR-338-5p expression was found significantly different in HS. Knowing the significance of the miRNA mechanism in inflammatory and immune progression, we suggest that miRNA profiles found in HS patients can be significant in understanding the pathogenesis modality and establishing efficient biomarkers for HS early diagnosis. In particular, miR-338-5p was closely related to HS invasiveness and production of cytokines and was atypically overexpressed. miR-338-5p may represent a good promise as a non-invasive clinical biomarker for HS.

Common variable immunodeficiency (CVID) is a complex primary immunodeficiency disorder characterized by a high clinical and genetic heterogeneity. The molecular underlying causes of CVID are not still now clear and the delays in diagnosis and treatment worsen the prognosis of the patients. MicroRNAs are non-coding, endogenous small RNAs often deregulated in human diseases, such as autoimmune and other immune-based disorders. In the present study, we aimed to evaluate miRNAs associated with the CVID and, in particular, with the response to the first Ig replacement therapy. To this aim, we compared miRNA profile obtained by serum samples of treatment-naïve CVID patients before and 24 h after the first Ig replacement therapy. For the first time, using a microarray assay followed by an integrated bioinformatics/biostatistics analysis, we identified five microRNAs (hsa-miR-6742, hsa-miR-1825, hsa-miR-4769-3p, hsa-miR-1228-3p, hsa-miR-1972) differently modulated in CVID patients by Ig infusion. All of them were down-regulated, excepted miR-6742 which was up-regulated. The latter may be of particular interest, since its functions are related to pathways involving Class I MHC mediated antigen processing and adaptive as well as innate Immune System. In conclusion, this study shows for the first time the modulation of miRNAs involved in CVID patients after the first Ig replacement therapy. Further studies are needed to assess whether such miRNAs could represent novel potential biomarkers in management and therapy of CVID patients.

Keloids are benign skin tumors that develop in individuals who have a positive family history of keloid disorders. Keloids are characterized by a deregulated wound-healing process, atypical fibroblasts with extreme deposition of extracellular matrix components, particularly collagen, increased cell proliferation and associated failure of apoptosis. Recently ingenol-mebutate has been used as a novel agent with anti-proliferative activity on human keloids as an alternative treatment option in patients, once conventional therapies have failed. We hypothesized that microRNAs (miR/miRNA) may be involved in the balance between lesion formation and repair. A comprehensive understanding of the molecular mechanism underlying the Ingenol-mebutate response in keloid fibroblast following Ingenol-mebutate exposure has been established previously. Therefore, the present study analyzed changes in miRNAs and apoptotic gene regulation in Ingenol-mebutate treated keloid fibroblast, by reverse transcription-quantitative polymerase chain reaction and a DNA fragmentation assay. The range of upregulated miRNAs and downregulated genes encoding cell death appeared to be associated with the degree of the morphological alterations in Ingenol-mebutate treated keloids. In particular, the upregulation of miR-34a was detected in keloid fibroblasts during and following Ingenol-mebutate exposure. Keloid fibroblasts that overexpressed miR-34a showed differential expression of genes involved in the apoptotic signaling pathway such as p53. In conclusion, the Ingenol-mebutate treatment used here was effective in reducing keloid fibroblast growth in cell culture experiments and the expression of particular miRNAs modulated the pro-apoptotic gene expression following Ingenol-mebutate treatment.

In this study, selenocystine, a nutritionally available selenoamino acid, was identified for the first time as a novel agent with anti proliferative activity on human keloids. The 20 μM concentration after 48. h treatment used here was the most effective to reduce keloid fibroblast growth. We analyzed the gene expression profile of selenocystine treatment response in keloid fibroblasts by the microarray system to characterize the effects of selenocystine on human keloids. The major alterations in keloid fibroblasts following selenocystine exposure included up-regulation of the genes encoding cell death and transcription factors. Prominent down-regulation of genes involved in development, cell adhesion and cytoskeleton, as well as extra cellular matrix genes, usually strongly up-regulated in keloids, resulted following selenocystine exposure. The range of the down-regulated genes and the degree of the decreased expression appeared to be correlated with the degree of the morphological alterations in selenocystine treated keloids. © 2011 Elsevier Inc.

The plant nuclear genome is largely composed of mobile DNA, which can rearrange genomes and other individual gene structure and also affect gene regulation through various promoted activities: transposition, insertion, excision, chromosome breakage, and ectopic recombination. Ty1-copia-like retrotransposon is a widespread class of transposable elements in the plant kingdom, representing a large part of the total DNA content. Here, a novel retrotransposon-like sequence was isolated and identified as the Ty1-copia-like reverse transcriptase domain (named here CLCoy1), based on the homology of known elements. Fluorescence in situ hybridization, revealed that CLCoy1 was mainly located in telomeric and sub-telomeric regions along the Citrus chromosomes. CLCoy1 composes 3.6% of the genome and, interestingly, while transposons are mostly specific to a species, this element was identified in other Citrus species such as Citrus aurantium, Fortunella margarita and Citrus paradisi, but undetected in Poncirus trifoliata. We also determined that wounding, salt and cell culture stress produced transcriptional activation of this novel retroelement in Citrus limon. The novel Ty1-copia-like element CLCoy1 may have played a major role in shaping genome structure and size during Citrus species evolution.

Repetitive sequences constitute a significant component of most eukaryotic genomes, and the isolation and characterization of repetitive DNA sequences provide an insight into the organization of the genome of interest. Here, we report the isolation and the molecular analysis and methylation status of a novel tandemly organized repetitive DNA sequence from the genome of Poncirus trifoliata. Digestion of P. trifoliata DNA with Afa I produced a prominent fragment of approximately 400 bp. Southern blotting analysis of genomic DNA digested with the same enzyme revealed a ladder composed of DNA fragments that are multimers of the 400-bp Afa I band, indicating that the repetitive DNA is arrayed in tandem. This suggests that Afa I isolated a novel satellite that we have called Poncirus trifoliata satellite DNA 400 (PN400). This satellite composes 25% of the genome and it is also present in lemon, sour orange and kumquat. Analysis of the methylation status demonstrated that the cytosines in CCGG sequences in this satellite were methylated. © Springer 2006.

Accumulating evidence shows an association between deregulation of miRNAs and exposure to environmental chemicals; miRNAs play a unique regulatory role in gene expression. Among environmental pollutants, dioxins are a family of compounds that are known to have multiple hazardous effects. Also, in utero exposure of the fetus to dioxins has been shown to cause impaired psychomotor development, decreased immune function and skin disease. miR-191 is a microRNA that has been found to be up-regulated by dioxin in hepatocellular carcinoma cells in vitro. Our study provides the first molecular evidence in vivo of a positive relationship between levels of polychlorinated biphenyls (PCBs) and miR-191 expression in human peripheral blood mononuclear cells. miR-191 expression was significantly correlated with blood concentrations of total PCB and, in particular, of 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169, a coplanar congener).Blood concentrations of PCB 169 correlated significantly with miR-191 expression in pregnant women living in a PCB-polluted area, who underwent therapeutic abortion due to fetal malformations. These data suggest that miRNAs could be potential biomarkers to clarify the mechanisms of environmental disease. © 2013 Elsevier B.V.

Biofuels are an important alternative, renewable source of energy in the face of the ongoing depletion of fossil fuels. Cheese whey is a dairy industry waste characterized by high lactose concentration, which represents a significant environmental problem. Bio-ethanol production by cheese whey could be an effective nonvegetable source for renewable energy production. Here, we report the isolation of a mixed microbial population, able to produce ethanol as main fermentation product from fermenting whey. The microbial consortium has been used to perform a batch fermentation of crude whey in both anoxic and hypoxic conditions. Maximum ethanol concentrations achieved in this study was obtained using the mixed culture in hypoxic conditions, grown at pH 4 and 30°C, with ethanol production yield of 60 g/L. Our research has pointed out an alternative way to both dispose and valorize cheese whey, a dairy by-product that could cause water pollution and harm to the environment if not properly treated. © 2012 Indian Academy of Sciences.

Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling adult-onset neurological disease. Accumulating evidence indicates that various miRNAs, expressed in a spatially and temporally controlled manner in the brain, play a key role in neuronal development. In addition, misregulation of microRNAs contributes to some mental disorders and neurodegeneration diseases. Here, we analyzed the expression profiles of 911 human miRNAs using microarray technology in leukocytes, the most readily available human tissue cells, obtained from 8 patients affected by sporadic amyotrophic lateral sclerosis (sALS) and 12 healthy controls. An independent group of 14 sALS patients and 14 controls was used for validation by TaqMan real-time polymerase chain reaction assay. We identified 8 miRNAs that were significantly up- or downregulated in sALS patients as compared to healthy controls. The significant variations in miRNAs profiles detected in leukocytes have been related to miRNAs predominantly expressed in the nervous system. One of these miRNAs, miR-338-3p, has previously been shown to be de-regulated in ALS brains. This study, for the first time, detected specific microRNAs disease-related changes at an earlier stage of sALS. We suggest that miRNAs profiles found in the peripheral blood leukocytes from sALS patients can be relevant to understand the pathogenesis of sALS and/or used as biomarkers of the disease Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling adult-onset neurological disease. Accumulating evidence indicates that various miRNAs, expressed in a spatially and temporally controlled manner in the brain, play a key role in neuronal development. In addition, misregulation of microRNAs contributes to some mental disorders and neurodegeneration diseases. Here, we analyzed the expression profiles of 911 human miRNAs using microarray technology in leukocytes, the most readily available human tissue cells, obtained from 8 patients affected by sporadic amyotrophic lateral sclerosis (sALS) and 12 healthy controls. An independent group of 14 sALS patients and 14 controls was used for validation by TaqMan real-time polymerase chain reaction assay. We identified 8 miRNAs that were significantly up- or downregulated in sALS patients as compared to healthy controls. The significant variations in miRNAs profiles detected in leukocytes have been related to miRNAs predominantly expressed in the nervous system. One of these miRNAs, miR-338-3p, has previously been shown to be de-regulated in ALS brains. This study, for the first time, detected specific microRNAs disease-related changes at an earlier stage of sALS. We suggest that miRNAs profiles found in the peripheral blood leukocytes from sALS patients can be relevant to understand the pathogenesis of sALS and/or used as biomarkers of the disease. © 2012 Elsevier B.V.

Several studies demonstrate links between environmental stress and index of reduced health, including risk factors for cardiovascular disease, reduced immune function and cancer risks. We investigated the hypothesis that pollution, as an environmental stress, impacts health by modulating the rate of cellular aging in healthy pregnant women. Our research looked at the effects that illegal waste sites have on the localized population of pregnant women in Campania, Italy. As is often the case in illegal dumping, the effects on the population are often seen well before knowing what specific agents in the soil and water are responsible. Here we provide evidence that the pollution in this region is significantly associated with higher oxidative stress, shorter telomere length and lower telomerase activity, which are known determinants of cell senescence and aging-related meiotic dysfunction in women, in peripheral blood mononuclear cells from healthy pregnant women, subjected to therapeutic abortion in the second trimester of pregnancy. These findings may have implications for understanding how, at the cellular level, environmental stress may promote earlier onset of age-related diseases. Several studies demonstrate links between environmental stress and index of reduced health, including risk factors for cardiovascular disease, reduced immune function and cancer risks. We investigated the hypothesis that pollution, as an environmental stress, impacts health by modulating the rate of cellular aging in healthy pregnant women. Our research looked at the effects that illegal waste sites have on the localized population of pregnant women in Campania, Italy. As is often the case in illegal dumping, the effects on the population are often seen well before knowing what specific agents in the soil and water are responsible. Here we provide evidence that the pollution in this region is significantly associated with higher oxidative stress, shorter telomere length and lower telomerase activity, which are known determinants of cell senescence and aging-related meiotic dysfunction in women, in peripheral blood mononuclear cells from healthy pregnant women, subjected to therapeutic abortion in the second trimester of pregnancy. These findings may have implications for understanding how, at the cellular level, environmental stress may promote earlier onset of age-related diseases. © 2012 Elsevier B.V.

Pharmaceuticals are continually released in the environment and therefore pollution from drugs is a pressing problem in the environment. Diclofenac, 2-[(2,6-dichlorophenyl) amino] phenylacetic acid is a FDA approved non-steroidal anti-inflammatory drug (NSAID) for the treatment of inflammation. This pharmaceutical has been found as pollutant in superficial waters. Danio rerio (zebrafish) embryo has been used as a model organism for acute pollutant toxicity tests in order to identify morphological alterations in development and death rate. Through the combination of mRNA differential display and quantitative Real Time experiments, we analyzed the alterations of gene expression in zebrafish embryos left to develop in the presence of diclofenac and thereby assess the molecular mechanism involved in ecotoxicity of diclofenac polluted waters. This approach, in embryos exposed to 1.25 mg/l drug for 48 h, allowed identifying 36 different genes, with both known and unknown functions, whose transcription is differentially regulated. The identity and ontological classification of these genes is presented. The wide variety of functional classes of transcripts isolated in this screen reflects the diverse spectrum of influences operating across diclofenac exposure. Of these 36 genes, several have been selected for detailed quantitative Real Time analysis to validate the screen. Our results, for the first time, provide an insight into some of the varied and novel molecular networks following zebrafish exposure to diclofenac polluted waters.

Monuments, works of art, and other cultural heritage are affected by microbial colonization that can, together with physical and chemical factors, cause serious structural and aesthetic damage. This is because cultural artifacts provide an inviting range of elements which microorganisms use in their metabolism through biosolubilization, e.g., elements such as calcium, aluminum, silicon, iron and potassium. Microorganisms can induce unsightly discolouration of building material and frescoes, formation of pigmented biofilms, biomineralization and degradation of organic binders leading to structural damage (Herrera et al. 2004). Microbial solubilization of materials involves the production of organic and inorganic acids by metabolic activity and is one of the leading biogeochemical mechanisms of rock decay. The bioreceptivity of a stone depends on its structure and chemical composition, air pollutants, moisture, and the varied elemental compositions of the stones provide a suitable environment for the microorganisms to develop. Moreover, phototrophic microorganisms may grow on the stone surface or may penetrate some millimetres into the rock pore system. These organisms can potentially contribute to the breakdown of rock crystalline structures. With time, the developing microorganisms cause the deterioration of the stones on which they reside by secreting enzymes and activating other metabolic activities by providing a suitable medium for their growth on the stone pores and surfaces (Dornieden et al. 2000; Warscheid and Braams 2000).

The p63 gene belongs to the p53 gene family and encodes for sequence-specific transcription factors. p63 has been characterized primarily in the context of epidermis where is implicated in the establishment of keratinocyte cell fate and in maintenance of epithelial self-renewal. ΔNp63 isoform has been showed to be involved in several kinds of human tumors of epidermal origin, even nonmalignant, for the neoplastic and proliferative potential. Here, we report the differential expression and the cellular localization of the ΔNp63 isoform in fibroblasts isolated from human keloids and hypertrophic scars compared to normal skin. Differently from hypertrophic scar, our results show that ΔNp63 has a nuclear localization and is overexpressed only in keloid fibroblasts, suggesting an essential role of ΔNp63 in vivo in human keloids. Consistent with our results, we hypothesize that ΔNp63 overexpression may be oncogenic because of its ability to block the activity of p53 since p53 is underexpressed in fibroblasts from keloids. © Mary Ann Liebert, Inc.