Do nomadic lactobacilli fit as potential vaginal probiotics? The answer lies in a successful selective multi-step and scoring approach.

BACKGROUND: The goal of this study was to create a multi-strain probiotic gel that would foster a lactobacilli-dominated vaginal microbiota in pregnant women and ensure appropriate eubiosis for the newborn. Nomadic lactobacilli (95 strains), mostly isolated from food sources, were preliminarily screened for functional traits before being characterized for their capability to inhibit the two vaginal pathogens Streptococcus agalactiae and Candida albicans, which may lead to adverse pregnancy-related outcomes. Eight best-performing strains were chosen and furtherly investigated for their ability to produce biofilm. Lastly, the two selected potential probiotic candidates were analyzed in vitro for their ability to reduce the inflammation caused by C. albicans infection on the reconstituted human vaginal epithelium (HVE). RESULTS: Lactiplantibacillus plantarum produced both isomers of lactic acid, while Lacticaseibacillus paracasei produced only L-isomer. The production of hydrogen peroxide was strain-dependent, with the highest concentrations found within Lact. paracasei strains. The auto-aggregation capacity and hydrophobicity traits were species-independent. S. agalactiae 88II3 was strongly inhibited both at pH 7.0 and 4.0, whereas the inhibition of C. albicans UNIBZ54 was less frequent. Overall, L. plantarum strains had the highest pathogen inhibition and functional scoring. L. plantarum C5 and POM1, which were selected as potential probiotic candidates also based on their ability to form biofilms, were able to counteract the inflammation process caused by C. albicans infection in the HVE model. CONCLUSIONS: Our multi-step and cumulative scoring-based approach was proven successful in mining and highlighting the probiotic potential of two nomadic lactobacilli strains (L. plantarum C5 and POM1), being applicable to preserve and improve human vaginal health.

Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer.

Valosin-containing protein (VCP)/p97, a member of the AAA+ ATPase family, is a molecular chaperone recruited to the endoplasmic reticulum (ER) membrane by binding to membrane adapters (nuclear protein localization protein 4 (NPL4), p47 and ubiquitin regulatory X (UBX) domain-containing protein 1 (UBXD1)), where it is involved in ER-associated protein degradation (ERAD). However, VCP/p97 interacts with many cofactors to participate in different cellular processes that are critical for cancer cell survival and aggressiveness. Indeed, VCP/p97 is reported to be overexpressed in many cancer types and is considered a potential cancer biomarker and therapeutic target. This review summarizes the role of VCP/p97 in different cancers and the advances in the discovery of small-molecule inhibitors with therapeutic potential, focusing on the challenges associated with cancer-related VCP mutations in the mechanisms of resistance to inhibitors.

The sourdough fermentation is the powerful process to exploit the potential of legumes, pseudo-cereals and milling by-products in baking industry.

In the era of fighting wastes and paying close attention to sustainability and new protein sources, legumes, pseudo-cereals and milling by-products deserve all the efforts for increasing their consumption. Even with obvious peculiarities, a common trait characterizes these heterogeneous matrixes: unquestionable nutritional and functional value combined with some technological, sensory and/or anti-nutritional weaknesses, which unfortunately limit the exploitation and consumption. With the perspective of their use to fortify staple baked goods, we reviewed the main technological, nutritional and functional features of various legumes and pseudo-cereals, and milling by-products. Notwithstanding the potential of other technological solutions, we reported numerous evidences that qualified the sourdough fermentation as the most sustainable and powerful process to exploit the technological, nutritional and functional features of these matrixes and to limit or eliminate weak attributes. Sourdough fermentations tailored for specific matrixes allowed the fortification of staple baked goods with abundant levels of legumes, pseudo-cereals or milling by-products while keeping high consumer acceptance.

Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer.

Selenoproteins are proteins that contain selenium within selenocysteine residues. To date, twenty-five mammalian selenoproteins have been identified; however, the functions of nearly half of these selenoproteins are unknown. Although alterations in selenoprotein expression and function have been suggested to play a role in cancer development and progression, few detailed studies have been carried out in this field. Network analyses and data mining of publicly available datasets on gene expression levels in different cancers, and the correlations with patient outcome, represent important tools to study the correlation between selenoproteins and other proteins present in the human interactome, and to determine whether altered selenoprotein expression is cancer type-specific, and/or correlated with cancer patient prognosis. Therefore, in the present study, we used bioinformatics approaches to (i) build up the network of interactions between twenty-five selenoproteins and identify the most inter-correlated proteins/genes, which are named HUB nodes; and (ii) analyze the correlation between selenoprotein gene expression and patient outcome in ten solid tumors. Then, considering the need to confirm by experimental approaches the correlations suggested by the bioinformatics analyses, we decided to evaluate the gene expression levels of the twenty-five selenoproteins and six HUB nodes in androgen receptor-positive (22RV1 and LNCaP) and androgen receptor-negative (DU145 and PC3) cell lines, compared to human nontransformed, and differentiated, prostate epithelial cells (EPN) by RT-qPCR analysis. This analysis confirmed that the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome predictions.

High-Value Compounds in Fruit, Vegetable and Cereal Byproducts: An Overview of Potential Sustainable Reuse and Exploitation.

Food waste (FW) represents a global and ever-growing issue that is attracting more attention due to its environmental, ethical, social and economic implications. Although a valuable quantity of bioactive components is still present in the residuals, nowadays most FW is destined for animal feeding, landfill disposal, composting and incineration. Aiming to valorize and recycle food byproducts, the development of novel and sustainable strategies to reduce the annual food loss appears an urgent need. In particular, plant byproducts are a plentiful source of high-value compounds that may be exploited as natural antioxidants, preservatives and supplements in the food industry, pharmaceuticals and cosmetics. In this review, a comprehensive overview of the main bioactive compounds in fruit, vegetable and cereal byproducts is provided. Additionally, the natural and suitable application of tailored enzymatic treatments and fermentation to recover high-value compounds from plant byproducts is discussed. Based on these promising strategies, a future expansion of green biotechnologies to revalorize the high quantity of byproducts is highly encouraging to reduce the food waste/losses and promote benefits on human health.

[Types and frequencies of complications associated with midline catheters and PICCs in a South Tyrolean district hospital: a retrospective cohort study]. / Arten und Häufigkeiten von Komplikationen bei Midline-Kathetern und PICCs in einem Südtiroler Bezirkskrankenhaus ­ eine retrospektive Kohortenstudie.

Types and frequencies of complications associated with midline catheters and PICCs in a South Tyrolean district hospital: a retrospective cohort study Abstract. BACKGROUND: Specialized registered nurses play a key role in the insertion and management of peripherally inserted central catheters (PICCs) and midline catheters in Anglo-Saxon countries. From the German-speaking area no data on the use of PICCs and midline catheters are available. AIM: The aim of this study was to describe the types and frequencies of complications of PICCs and midline catheters which were inserted by specialized registered nurses in a South Tyrolean district hospital. METHODS: We performed a retrospective cohort study of PICCs and midline catheters inserted between 2013 and 2015 in one surgical unit in the district hospital Bruneck (South Tyrol / Italy). RESULTS: Data from 900 catheters (421 midline catheters and 479 PICCs) inserted in 686 adult patients (404 women, 282 men) were analysed. The cumulative incidence was 29.2 % complications for midline catheters (incidence rate: 13 complications / 1000 catheter days) and 16.0 % for PICCs (incidence rate: 3 complications / 1000 catheter days). The most frequent complication was the removal of the catheter by the patients (PICCs: 6.7 %, midline catheters: 15.7 %). Other less frequent complications were mechanical complications, occlusions, infections and thromboses. CONCLUSIONS: This study in one district hospital revealed similar types and frequencies of complications as previous international studies. Specialized and clinically competent nurses in German-speaking countries could develop advanced roles in the insertion and management of PICCs and midline catheters.

The Effect of Light Exposure at Night (LAN) on Carcinogenesis via Decreased Nocturnal Melatonin Synthesis.

In mammals, a master clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus, a region that receives input from the retina that is transmitted by the retinohypothalamic tract. The SCN controls the nocturnal synthesis of melatonin by the pineal gland that can influence the activity of the clock's genes and be involved in the inhibition of cancer development. On the other hand, in the literature, some papers highlight that artificial light exposure at night (LAN)-induced circadian disruptions promote cancer. In the present review, we summarize the potential mechanisms by which LAN-evoked disruption of the nocturnal increase in melatonin synthesis counteracts its preventive action on human cancer development and progression. In detail, we discuss: (i) the Warburg effect related to tumor metabolism modification; (ii) genomic instability associated with L1 activity; and (iii) regulation of immunity, including regulatory T cell (Treg) regulation and activity. A better understanding of these processes could significantly contribute to new treatment and prevention strategies against hormone-related cancer types.

Immobilized Hydrolytic Enzymes Exhibit Antibiofilm Activity Against Escherichia coli at Sub-Lethal Concentrations.

The effects of two commercially available immobilized enzymes (namely the glycosidase pectinase and the protease subtilisin A) at sub-lethal concentrations were investigated in terms of their influence on biofilm genesis, on the composition of the biofilm matrix, and their antibiotic synergy against Escherichia coli biofilm, used as a model system of bacterial biofilms. The best antibiofilm performance of solid-supported hydrolases was obtained at the surface concentration of 0.022 and 0.095 U/cm(2) with a reduction of 1.2 and 2.3 log CFU/biofilm for pectinase and subtilisin, respectively. At these enzyme surface concentrations, the biocatalysts affected the structural composition of the biofilm matrix, impacting biofilm thickness. Finally, the immobilized hydrolases enhanced biofilm sensitivity to a clinically relevant concentration of the antibiotic ampicillin. At the final antibiotic concentration of 0.1 mg/ml, a reduction of 2 and 3.5 log10 units in presence of 0.022 Upectinase/cm(2) and 0.095 Usubtilisin/cm(2) was obtained, respectively, in comparison the antibiotic alone. Immobilized pectinase and subtilisin at sub-lethal concentrations demonstrated a great potential for antibiofilm applications.

Assessing the microbiological risk to stored sixteenth century parchment manuscripts: a holistic approach based on molecular and environmental studies.

The microbial risk for the conservation of seven sixteenth century parchment manuscripts, which showed brown discolouration putatively caused by microorganisms, was evaluated using non-invasive sampling techniques, microscopy, studies of surface-associated and airborne microflora with culture-independent molecular methods, and by measuring repository thermo-hygrometric values. Microscopic observations and ATP assays demonstrated a low level of contamination, indicating that the discolouration was not related to currently active microbial colonisation. Nevertheless, a culture-independent molecular approach was adopted to fully characterise surface-associated communities searching for biodeteriogens that could grow under appropriate thermo-hygrometric conditions. Indeed, potential biodeteriogens and microorganisms that are ecologically related to humans were found, suggesting the need to control the conservation environment and improve handling procedures. Microbial loads of air and thermo-hygrometric measurements showed that the repository was not suitable for preventing the microbial deterioration of parchment. A holistic approach to the assessment of risk of microbial deterioration of documents and heritage preservation is proposed for the first time.

Evaluation of zosteric acid for mitigating biofilm formation of Pseudomonas putida isolated from a membrane bioreactor system.

This study provides data to define an efficient biocide-free strategy based on zosteric acid to counteract biofilm formation on the membranes of submerged bioreactor system plants. 16S rRNA gene phylogenetic analysis showed that gammaproteobacteria was the prevalent taxa on fouled membranes of an Italian wastewater plant. Pseudomonas was the prevalent genus among the cultivable membrane-fouler bacteria and Pseudomonas putida was selected as the target microorganism to test the efficacy of the antifoulant. Zosteric acid was not a source of carbon and energy for P. putida cells and, at 200 mg/L, it caused a reduction of bacterial coverage by 80%. Biofilm experiments confirmed the compound caused a significant decrease in biomass (-97%) and thickness (-50%), and it induced a migration activity of the peritrichous flagellated P. putida over the polycarbonate surface not amenable to a biofilm phenotype. The low octanol-water partitioning coefficient and the high water solubility suggested a low bioaccumulation potential and the water compartment as its main environmental recipient and capacitor. Preliminary ecotoxicological tests did not highlight direct toxicity effects toward Daphnia magna. For green algae Pseudokirchneriella subcapitata an effect was observed at concentrations above 100 mg/L with a significant growth of protozoa that may be connected to a concurrent algal growth inhibition.

Tailor-made fermentation of sourdough reduces the acrylamide content in rye crispbread and improves its sensory and nutritional characteristics.

Thirty strains of lactic acid bacteria (LAB) and Saccharomyces cerevisiae E8.9 (wild type) were used to formulate fifteen combinations of starters by mixing two or three LAB with the yeast (ratio LAB: yeast, 10: 1). Such combinations were used to prepare rye sourdough and their performance in term of acidification and biochemical characteristics during fermentation at two temperatures (30 and 37 °C) and duration (4 and 8 h) were screened. The best thirteen sourdough formulations were selected and used for rye crispbread making. The analysis of acrylamide concentration demonstrated that 11 out 13 formulations resulted in significant decreases of concentration compared to the baker's yeast (control), with reductions up to 79.6 %. The rye sourdough crispbreads showed also higher amount of volatile organic compounds (VOCs) compared to the baker's yeast control. Two rye sourdough crispbreads, selected to represent the opposite extremes within the thirteen formulations in term of VOC profiles and fermentation performances, demonstrated better sensory and nutritional features, such as phytic acid reduction (up to 47.3 %), and enhanced total free amino acid compared to the control. These evidences suggest the potential of tailored sourdough fermentations as alternative and suitable biotechnological strategy for lowering acrylamide levels in rye crispbread.

In vitro gastrointestinal gas monitoring with carbon nanotube sensors.

In vitro simulators of the human gastrointestinal (GI) tract are remarkable technological platforms for studying the impact of food on the gut microbiota, enabling continuous and real-time monitoring of key biomarkers. However, comprehensive real-time monitoring of gaseous biomarkers in these systems is required with a cost-effective approach, which has been challenging to perform experimentally to date. In this work, we demonstrate the integration and in-line use of carbon nanotube (CNT)-based chemiresitive gas sensors coated with a thin polydimethylsiloxane (PDMS) membrane for the continuous monitoring of gases within the Simulator of the Human Microbial Ecosystem (SHIME). The findings demonstrate the ability of the gas sensor to continuously monitor the different phases of gas production in this harsh, anaerobic, highly humid, and acidic environment for a long exposure time (16 h) without saturation. This establishes our sensor platform as an effective tool for real-time monitoring of gaseous biomarkers in in vitro systems like SHIME.

Novel probiotic preparation with in vivo gluten-degrading activity and potential modulatory effects on the gut microbiota.

Gluten possesses unique properties that render it only partially digestible. Consequently, it exerts detrimental effects on a part of the worldwide population who are afflicted with celiac disease (1%) or related disorders (5%), particularly due to the potential for cross-contamination even when adhering to a gluten-free diet (GFD). Finding solutions to break down gluten during digestion has a high nutritional and social impact. Here, a randomized double-blind placebo-controlled in vivo challenge investigated the gluten-degrading activity of a novel probiotic preparation comprising lactobacilli and their cytoplasmic extracts, Bacillus sp., and bacterial protease. In our clinical trial, we collected feces from 70 healthy volunteers at specific time intervals. Probiotic/placebo administration lasted 32 days, followed by 10 days of wash-out. After preliminary GFD to eliminate residual gluten from feces, increasing amounts of gluten (50 mg-10 g) were administered, each one for 4 consecutive days. Compared to placebo, the feces of volunteers fed with probiotics showed much lower amounts of residual gluten, mainly with increased intakes. Probiotics also regulate the intestinal microbial communities, improving the abundance of genera pivotal to maintaining homeostasis. Quantitative PCR confirmed that all probiotics persisted during the intervention, some also during wash-out. Probiotics promoted a fecal metabolome with potential immunomodulating activity, mainly related to derivatives of branched-chain amino acids and short-chain fatty acids. IMPORTANCE: The untapped potential of gluten-degrading bacteria and their application in addressing the recognized limitations of gluten-related disorder management and the ongoing risk of cross-contamination even when people follow a gluten-free diet (GFD) emphasizes the significance of the work. Because gluten, a common protein found in many cereals, must be strictly avoided to stop autoimmune reactions and related health problems, celiac disease and gluten sensitivity present difficult hurdles. However, because of the hidden presence of gluten in many food products and the constant danger of cross-contamination during food preparation and processing, total avoidance is frequently challenging. Our study presents a novel probiotic preparation suitable for people suffering from gluten-related disorders during GFD and for healthy individuals because it enhances gluten digestion and promotes gut microbiota functionality.

The Effect of Hydrolyzed and Fermented Arabinoxylan-Oligo Saccharides (AXOS) Intake on the Middle-Term Gut Microbiome Modulation and Its Metabolic Answer.

Although fermentation and hydrolyzation are well-known processes to improve the bioavailability of nutrients and enable the fortification with dietary fibers, the effect of such pre-treatments on the prebiotic features of arabinoxylan-oligosaccharides (AXOS) had not been explored. The middle-term in vitro simulation through the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) demonstrated that the feeding with different formulations (namely oat bran, rye bran and wheat bran) containing hydrolyzed AXOS fermented by lactic acid bacteria significantly increased the synthesis of short-chain fatty acids (SCFA) by colon microbiota, with hydrolyzed and fermented rye bran displaying the highest effect. After two weeks from the interruption of intake, SCFA concentrations significantly decreased but remained still significantly higher compared to the original condition. The microbiome was also affected, with a significant abundance increase in Lactobacillaceae taxon after feeding with all fermented and hydrolyzed formulates. Hydrolyzed and fermented rye bran showed the highest changes. The fungal community, even if it had a lower variety compared to bacteria, was also modulated after feeding with AXOS formulations, with an increase in Candida relative abundance and a decrease in Issatchenkia. On the contrary, the intake of non-hydrolyzed and non-fermented wheat bran did not produce relevant changes of relative abundances. After two weeks from intake interruption (wash out period) such changes were mitigated, and the gut microbiome modulated again to a final structure that was more like the original condition. This finding suggests that hydrolyzed AXOS fermented by lactic acid bacteria could have a more powerful prebiotic effect compared to non-hydrolyzed and non-fermented wheat bran, shaping the colon microbiome and its metabolic answer. However, the intake should be continuous to assure persistent effects. Opening a window into the ecological evolutions and plausible underlying mechanisms, the findings reinforce the perspective to explore more in depth the use of hydrolyzed and fermented AXOS as additional ingredient for bread fortification.

Sourdough "Biga" Fermentation Improves the Digestibility of Pizza Pinsa Romana: An Investigation through a Simulated Static In Vitro Model.

Baked goods manufacturing parameters and fermentation conditions interfere with the nutrients content and affect their gastrointestinal fate. Pinsa Romana is a type of pizza that, recently, has been commercially rediscovered and that needed elucidation from a nutritional and digestibility perspective. In this study, six types of Pinsa Romana (five made with indirect method and one produced with straight dough technology) were characterized for their biochemical and nutritional features. Several variables like indirect (biga) Pinsa Romana production process, fermentation time and use of sourdough were investigated. The Pinsa Romana made with biga including sourdough and fermented for 48 h at 16 °C ((PR_48(SD)) resulted in the lowest predicted glycemic index, in the highest content of total peptides, total and individual free amino acids and gamma-amino butyric acid (GABA), and in the best protein quality indexes (protein efficiency ratio and nutritional index). The static in vitro digestion showed that the digesta from PR_48(SD) confirmed a reduced in vitro glycemic response after intake, and it showed a lower bioavailability of hydrophilic peptides. Furthermore, the inclusion of sourdough in biga enhanced the bioavailability of protein-related end-products including human health promoting compounds such as essential amino acids.

Use of Raw Peach Gum as a Sustainable Additive for the Development of Water-Sensitive and Biodegradable Thermoplastic Starch Films.

In this study, formulations of thermoplastic starch (TPS) with 5, 10, and 15 parts per hundred resin (phr) of raw peach gum (PG) were prepared by melt extrusion followed by injection molding to obtain standard specimens for characterization. In addition, biodegradable films were developed by compression molding. It was determined that TPS with 5 phr and 10 phr of PG presented similar mechanical behavior to pure TPS after the processing. However, results indicated that adding PG in 10 phr slowed down the starch's retrogradation, delaying the TPS structure's stiffening. Moreover, the TPS-PG formulations presented improved solubility, which increased by 24% with 10 and 15 phr of PG compared to that shown for TPS. Additionally, PG enhanced the compostability of TPS, causing the sample to disintegrate in a shorter period. In conclusion, it was determined that raw PG added in 10 phr could be added as a sustainable additive to modify the biodegradation and water sensitivity of TPS without affecting its mechanical behavior after processing and delaying the retrogradation of the TPS structure, increasing its shelf life.

Chlorpromazine affects glioblastoma bioenergetics by interfering with pyruvate kinase M2.

Glioblastoma (GBM) is the most frequent and lethal brain tumor, whose therapeutic outcome - only partially effective with current schemes - places this disease among the unmet medical needs, and effective therapeutic approaches are urgently required. In our attempts to identify repositionable drugs in glioblastoma therapy, we identified the neuroleptic drug chlorpromazine (CPZ) as a very promising compound. Here we aimed to further unveil the mode of action of this drug. We performed a supervised recognition of the signal transduction pathways potentially influenced by CPZ via Reverse-Phase Protein microArrays (RPPA) and carried out an Activity-Based Protein Profiling (ABPP) followed by Mass Spectrometry (MS) analysis to possibly identify cellular factors targeted by the drug. Indeed, the glycolytic enzyme PKM2 was identified as one of the major targets of CPZ. Furthermore, using the Seahorse platform, we analyzed the bioenergetics changes induced by the drug. Consistent with the ability of CPZ to target PKM2, we detected relevant changes in GBM energy metabolism, possibly attributable to the drug's ability to inhibit the oncogenic properties of PKM2. RPE-1 non-cancer neuroepithelial cells appeared less responsive to the drug. PKM2 silencing reduced the effects of CPZ. 3D modeling showed that CPZ interacts with PKM2 tetramer in the same region involved in binding other known activators. The effect of CPZ can be epitomized as an inhibition of the Warburg effect and thus malignancy in GBM cells, while sparing RPE-1 cells. These preclinical data enforce the rationale that allowed us to investigate the role of CPZ in GBM treatment in a recent multicenter Phase II clinical trial.

Importance of subaerial biofilms and airborne microflora in the deterioration of stonework: a molecular study.

The study characterized the sessile microbial communities on mortar and stone in Milan University's Richini's Courtyard and investigated the relationship between airborne and surface-associated microbial communities. Active colonization was found in three locations: green and black patinas were present on mortar and black spots on stone. Confocal laser scanning microscopy, scanning electron microscopy and culture-independent molecular methods revealed that the biofilm causing deterioration was dominated by green algae and black fungi. The mortar used for restoration contained acrylic and siloxane resins that could be used by microorganisms as carbon and energy sources thereby causing proliferation of the biofilm. Epifluorescence microscopy and culture-based methods highlighted a variety of airborne microflora. Bacterial and fungal counts were quantitatively similar to those reported in other investigations of urban areas, the exception being fungi during summer (1-2 orders of magnitude higher). For the first time in the cultural heritage field, culture-independent molecular methods were used to resolve the structure of airborne communities near discoloured surfaces, and to investigate the relationship between such communities and surface-associated biofilms.

Biofilm formation as an extra gear for Apilactobacillus kunkeei to counter the threat of agrochemicals in honeybee crop.

The alteration of a eubiosis status in honeybees' gut microbiota is directly linked to the occurrence of diseases, and likely to the honeybees decline. Since fructophilic lactobacilli were suggested as symbionts for honeybees, we mechanistically investigated their behaviour under the exposure to agrochemicals (Roundup, Mediator and Reldan containing glyphosate, imidacloprid and chlorpyrifos-methyl as active ingredients respectively) and plant secondary metabolites (nicotine and p-coumaric acid) ingested by honeybees as part of their diet. The effects of exposure to agrochemicals and plant secondary metabolites were assessed both on planktonic cells and sessile communities of three biofilm-forming strains of Apilactobacillus kunkeei. We identified the high sensitivity of A. kunkeei planktonic cells to Roundup and Reldan, while cells embedded in mature biofilms had increased resistance to the same agrochemicals. However, agrochemicals still exerted a substantial inhibitory/control effect if the exposure was during the preliminary steps of biofilm formation. The level of susceptibility resulted to be strain-specific. Exopolysaccharides resulted in the main component of extracellular polymeric matrix (ECM) in biofilm, but the exposure to Roundup caused a change in ECM production and composition. Nicotine and p-coumaric acid had a growth-promoting effect in sessile communities, although no effect was found on planktonic growth.

An Integrated In Silico, In Vitro and Tumor Tissues Study Identified Selenoprotein S (SELENOS) and Valosin-Containing Protein (VCP/p97) as Novel Potential Associated Prognostic Biomarkers in Triple Negative Breast Cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is a heterogeneous group of tumors with early relapse, poor overall survival, and lack of effective treatments. Hence, new prognostic biomarkers and therapeutic targets are needed. METHODS: The expression profile of all twenty-five human selenoproteins was analyzed in TNBC by a systematic approach.In silicoanalysis was performed on publicly available mRNA expression datasets (Cancer Cell Line Encyclopedia, CCLE and Library of Integrated Network-based Cellular Signatures, LINCS). Reverse transcription quantitative PCR analysis evaluated selenoprotein mRNA expression in TNBC versus non-TNBC and normal breast cells, and in TNBC tissues versus normal counterparts. Immunohistochemistry was employed to study selenoproteins in TNBC tissues. STRING and Cytoscape tools were used for functional and network analysis. RESULTS: GPX1, GPX4, SELENOS, TXNRD1 and TXNRD3 were specifically overexpressed in TNBC cells, tissues and CCLE/LINCS datasets. Network analysis demonstrated that SELENOS-binding valosin-containing protein (VCP/p97) played a critical hub role in the TNBCselenoproteins sub-network, being directly associated with SELENOS expression. The combined overexpression of SELENOS and VCP/p97 correlated with advanced stages and poor prognosis in TNBC tissues and the TCGA dataset. CONCLUSION: Combined evaluation of SELENOS and VCP/p97 might represent a novel potential prognostic signature and a therapeutic target to be exploited in TNBC.