The aim of this study was to elucidate the prognostic impact of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and aldehyde dehydrogenase-1 (ALDH1) in colorectal cancer.
A tissue ...microarray of 1420 primary colorectal cancers and 57 normal mucosa samples was immunostained for CD133, CD166, CD44s, EpCAM, and ALDH1 in addition to 101 corresponding whole tissue sections. Invasive potential of three colorectal cancer cell lines was tested.
Differences between normal tissue and cancer were observed for all markers (P<0.001). Loss of membranous CD166 and CD44s were linked to higher pT (P=0.002, P=0.014), pN (P=0.004, P=0.002), an infiltrating growth pattern (P<0.001, P=0.002), and worse survival (P=0.015, P=0.019) in univariate analysis only. Loss of membranous EpCAM expression was also linked to higher pN (P=0.023) and infiltrating growth pattern (P=0.005). The CD44s, CD166, and EpCAM expression were lost towards the invasive front. The CD44-/CD166- cells from three colorectal cancer cell lines exhibited significantly higher invasive potential in vitro than their positive counterparts.
Loss, rather than overexpression, of membranous CD44s, CD166, and EpCAM is linked to tumour progression. This supports the notion that the membranous evaluation of these proteins assessed by immunohistochemistry may be representative of their cell adhesion rather than their intra-cellular functions.
Abstract Objective To study the in vivo osteoinductive potential, bone-bonding ability (bioactivity) and bone biomineralization of current hydraulic calcium silicate cements used as graft materials ...and placed in contact with medullary bone. Methods ProRoot MTA, MTA Plus and Biodentine were used to fill surgical bone defects (2-mm diameter through the entire cortical thickness to reach the medullary bone) in the tibia of mature male rabbits. Tibiae were retrieved after 30 days and submitted to histological analysis and microchemical characterization using Optical Microscopy (OM) and Environmental Scanning Electron Microscopy with Energy Dispersive X-ray analysis (ESEM-EDX). Bone neoformation and histomorphometric evaluations, degree of mineralization (by Ca/P, Ca/N and P/N ratios) and the diffusion of material elements were studied. Results Bone neoformation was observed in response to all materials. No sign of necrosis were found on the walls of the pre-existing cortical bone. No osteoclasts and no formation of fibrous tissue were evident. Sign of angiogenesis were present. EDX (element content, line profile and element mapping) showed the increase in Ca and P and decrease in C, S and N from the mature bone towards the mineralizing interface. Ca/P, Ca/N and P/N ratios showed differences in the degree of mineralization/maturation stage of bone. MTA Plus and ProRoot MTA exhibited close contact with the pre-existing bone and good bone-bonding with neoformed bone juxtaposed on the medullary side of the materials without interposed connective tissue or resorption lacunae or gaps. The materials showed a dense appearance with 100% of residual materials and no colonization by fluids and cells. No migration of Bi or Al material elements to the newly formed bone was found. Biodentine showed newly formed trabecular bone with marrow spaces and sparse traces of residual material (≈9%). Significance The in vivo osteoinductive properties with dynamic biomineralization processes around these calcium silicate materials extruded in medullary bone in appropriate animal model have been demonstrated by ESEM-EDX in association with OM. Good biocompatibility was evident as only slight inflammatory infiltrate and no sign of necrosis at the interface with the pre-existing bone were found. MTA Plus and ProRoot MTA exhibited bioactive potential as they can bond to bone directly without interposed connective tissue. Biodentine was replaced by newly formed bone. Clinical significance The results of the study demonstrate the capacity of calcium silicate cements to allow osteoid matrix deposition by activated osteoblasts and favour its biomineralization, and to achieve a direct bond between the (bioactive) materials surface and the mineralized bone matrix.
The immune contexture predicts prognosis in human colorectal cancer (CRC). Whereas tumour-infiltrating CD8+ T cells and myeloid CD16+ myeloperoxidase (MPO)+ cells are associated with favourable ...clinical outcome, interleukin (IL)-17-producing cells have been reported to correlate with severe prognosis. However, their phenotypes and functions continue to be debated.
To investigate clinical relevance, phenotypes and functional features of CRC-infiltrating, IL-17-producing cells.
IL-17 staining was performed by immunohistochemistry on a tissue microarray including 1148 CRCs. Phenotypes of IL-17-producing cells were evaluated by flow cytometry on cell suspensions obtained by enzymatic digestion of clinical specimens. Functions of CRC-isolated, IL-17-producing cells were assessed by in vitro and in vivo experiments.
IL-17+ infiltrates were not themselves predictive of an unfavourable clinical outcome, but correlated with infiltration by CD8+ T cells and CD16+ MPO+ neutrophils. Ex vivo analysis showed that tumour-infiltrating IL-17+ cells mostly consist of CD4+ T helper 17 (Th17) cells with multifaceted properties. Indeed, owing to IL-17 secretion, CRC-derived Th17 triggered the release of protumorigenic factors by tumour and tumour-associated stroma. However, on the other hand, they favoured recruitment of beneficial neutrophils through IL-8 secretion and, most importantly, they drove highly cytotoxic CCR5+CCR6+CD8+ T cells into tumour tissue, through CCL5 and CCL20 release. Consistent with these findings, the presence of intraepithelial, but not of stromal Th17 cells, positively correlated with improved survival.
Our study shows the dual role played by tumour-infiltrating Th17 in CRC, thus advising caution when developing new IL-17/Th17 targeted treatments.
We present the variation in trace element partition coefficients measured at the interface between rapidly cooled clinopyroxene crystals and co-existing melts. Results indicate that, as the cooling ...rate is increased, clinopyroxene crystals are progressively depleted in Si, Ca and Mg counterbalanced by enrichments in Al (mainly tetrahedral Al
iv
), Na and Ti. Partition coefficients (Ds) for rare earth elements (REE), high field strength elements (HFSE) and transition elements (TE) increase with increasing cooling rate, in response to clinopyroxene compositional variations. The entry of REE into the M2 site is facilitated by a coupled substitution where either Na substitutes for Ca on the M2 site or Al
iv
substitutes for Si in the tetrahedral site. The latter substitution reflects an increased ease of locally balancing the excess charge at M2 as the number of surrounding Al
iv
atoms increases. Due to the lower concentration of Ca in rapidly cooled clinopyroxenes, divalent large ion lithophile elements (LILE) on M2 decrease at the expense of monovalent cations. Conversely, higher concentrations of HFSE and TE on the M1 site are facilitated as the average charge on this site increases with the replacement of divalent-charged cations by Al
vi
. Although crystallization kinetics modify clinopyroxene composition, deviations from equilibrium partitioning are insufficient to change the tendency of a trace element to be compatible or incompatible. Consequently, there are regular relationships between ionic radius, valence of the trace element and D. At both equilibrium and cooling rate conditions, Ds for isovalent cations define parabola-like curves when plotted against ionic radius, consistent with the lattice strain model, demonstrating that the partitioning of trace elements is driven by charge balance mechanisms; cation substitution reactions can be treated in terms of the energetics of the various charge-imbalanced configurations.
•Petrography of Construction and Demolition Wastes (CDWs)•Characterization of CDWs through XRPD and XRF analysis methodologies.•Proposal general protocol to analyse the petrography of CDW worldwide.
...The density, colour and texture, plus mineral and chemical features of 18 ceramic-like CDW samples from the Abruzzo region (Central Italy) were characterised. The concretes, natural stones, tiles, roof-tiles, bricks and perforated bricks are either aphanitic to porphyric. Concretes and natural stones are grey to white and tend to be > 2.0 g/cm3; the masonries are brown to reddish and close to < 2.0 g/cm3. Concrete and natural stone are rich or even exclusively made up of calcite, with high amounts of CaO (>40 wt%) and LOI (volatiles, CO2 + H2O). The masonries are instead calcite-, CaO- (<25 wt%) and LOI-poor (<8 wt%) but enriched in SiO2 (45 to 70 wt%) stabilised as quartz and/or cristobalite, with significant amount of Al2O3 (12 to 20 wt%). S and Cl contents are similar among concrete, bricks and perforated bricks.
The petrography of CDW concretes is similar among geographical areas with abundance of limestones used as aggregates. However, in limestone-poor areas CDW are SiO2- and Al2O3-rich, reflecting the prevalent use of masonry and/or silicate-rich construction materials, implying that each geographical area is characterised by peculiar CDW composition. Therefore, the knowledge of mesoscopic, physical and petrographic aspects has to be known for planning adequate sorting methods, promoting upcycling reusing applications. Some of the studied CDW samples are susceptible to release relative high Cr and As content.
Antibiotic resistance is a major public health problem worldwide and the finding of alternative methods for eliminating bacteria is one of the prerogatives of medical research. The indiscriminate use ...of antibiotics in dentistry, especially for the treatment of peri-implantitis, could lead to superinfections.
Alternative methods, like photodynamic therapy mediated by the use of aminolevulinic acid and a red light has been largely described, especially in dentistry, but results were encouraging against Gram-positive bacteria, but limited against Gram-negative.
The effectiveness of photodynamic therapy mediated by a novel product containing aminolevulinic acid, Aladent (ALAD) has been tested in this in vitro study, against different types of bacteria particularly involved in the infections of the oral cavity and peri-implantitis. The novelty of ALAD is the marked hydrophilicity that should increase the passage of the molecule through the membrane pores of Gram-negative bacteria.
Considering the novelty of the product a preliminary experiment permitted to test the effectiveness against Enterococcus faecalis after 1 h of ALAD incubation at different concentrations, with or without different timings of LED irradiation. The count of CFUs and the live/dead observation with fluorescent microscopy showed a significant reduction and killing of bacterium.
Then, in the second stage, that could meet the necessity of effectiveness and the clinician's requests to reduce the timing of treatment, ALAD, with and without irradiation, was tested on Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Veillonella parvula and Porphyromonas gingivalis.
In particular, the efficiency of different concentrations of the product after a 25 min incubation was tested with and without the adjunctive LED irradiation for 5 min.
A slight ALAD bactericidal effect was reported for all bacteria, also without LED irradiation, however, the most effective treatment was 25 min of 50% ALAD incubation followed by 5 min of a red LED.
The in vitro tests demonstrated that ALAD gel with LED irradiation exerts a potent antibacterial activity on different bacteria, both Gram-positive and Gram-negative.
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•ALAD with LED irradiation exerted a potent antibacterial activity both Gram+ and -.•The higher effect was obtained with 1 h of gel plus 7 min of LED irradiation.•25 min ALAD plus 5 min of LED led to a high antibacterial effect.•A certain antibacterial effect was measure also without LED.
The physical integrity of a sub-volcanic basement is crucial in controlling the stability of a volcanic edifice. For many volcanoes, this basement can comprise thick sequences of carbonates that are ...prone to significant thermally-induced alteration. These debilitating thermal reactions, facilitated by heat from proximal magma storage volumes, promote the weakening of the rock mass and likely therefore encourage edifice instability. Such instability can result in slow, gravitational spreading and episodic to continuous slippage of unstable flanks, and may also facilitate catastrophic flank collapse. Understanding the propensity of a particular sub-volcanic basement to such instability requires a detailed understanding of the influence of high temperatures on the chemical, physical, and mechanical properties of the rocks involved. The juxtaposition of a thick carbonate substratum and magmatic heat sources makes Mt. Etna volcano an ideal candidate for our study. We investigated experimentally the effect of temperature on two carbonate rocks that have been chosen to represent the deep, heterogeneous sedimentary substratum under Mt. Etna volcano. This study has demonstrated that thermal-stressing resulted in a progressive and significant change in the physical properties of the two rocks. Porosity, wet (i.e., water-saturated) dynamic Poisson's ratio and wet Vp/Vs ratio all increased, whilst P- and S-wave velocities, bulk sample density, dynamic and static Young's modulus, dry Vp/Vs ratio, and dry dynamic Poisson's ratio all decreased. At temperatures of 800°C, the carbonate in these rocks completely dissociated, resulting in a total mass loss of about 45% and the release of about 44wt.% of CO2. Uniaxial deformation experiments showed that high in-situ temperatures (>500°C) significantly reduced the strength of the carbonates and altered their deformation behaviour. Above 500°C the rocks deformed in a ductile manner and the output of acoustic emissions was greatly reduced. We speculate that thermally-induced weakening and the ductile behaviour of the carbonate substratum could be a key factor in explaining the large-scale deformation observed at Mt. Etna volcano. Our findings are consistent with several field observations at Mt. Etna volcano and can quantitatively support the interpretation of (1) the irregularly low seismic velocity zones present within the sub-volcanic sedimentary basement, (2) the anomalously high CO2 degassing observed, (3) the anomalously high Vp/Vs ratios and the rapid migration of fluids, and (4) the increasing instability of volcanic edifices in the lifespan of a magmatic system. We speculate that carbonate sub-volcanic basement may emerge as one of the decisive fundamentals in controlling volcanic stability.
► High temperatures strongly influence sub-volcanic carbonate successions. ► Thermal weakening could encourage large-scale deformation at Mt. Etna. ► Geophysical anomalies/observations can be explained by such thermal degradation. ► Decarbonation should not be dismissed in CO2 budgets for Mt. Etna. ► Carbonate basements may emerge as a decisive fundamental in volcanic stability.
The tumour-host interaction at the invasive front of colorectal cancer, including the epithelial-mesenchymal transition and its hallmark 'tumour budding', is an important area of investigation in ...terms of prognosis. The aim of this study was to determine the prognostic impact of a 'pro-/anti-tumour' approach defined by an established 'pro-tumour' (tumour budding) and host-related 'anti-tumour' factor of the adaptive immunological microenvironment (CD8+ lymphocytes).
Double immunostaining for CK22/CD8 on whole tissue sections (n=279; Cohort 1) and immunohistochemistry for CD8+ using tissue microarrays (n=191; Cohort 2) was carried out. Tumour buds, CD8+ and CD8+ T-lymphocytes : tumour buds indices were evaluated per high-power field.
In Cohort 1, a low-CD8+/ buds index was associated with lymph node metastasis (P<0.001), vascular invasion (P=0.009), worse survival in univariate (P<0.001) and multivariable (P<0.001) analysis, and furthermore in lymph node-negative patients (P=0.002). In Cohort 2, the CD8+/ buds index was associated with T stage (P<0.001), N stage (P=0.041), vascular invasion (P=0.005) and survival in patients with TNM stage II (P=0.019), stage III (P=0.004), and adjuvantly untreated (P=0.009) and treated patients (P<0.001).
The CD8+ lymphocyte : tumour-budding index is an independent prognostic factor in colorectal cancer and a promising approach for a future prognostic score for patients with this disease.
Background
The aim of this study was to investigate for the first time the histological response of human periodontium to mineral trioxide aggregate (MTA) and Biodentine.
Methods
Six patients ...scheduled for implant full‐arch rehabilitation were randomly assigned to one of the two test groups: MTA or Biodentine treatment. For each patient, two teeth scheduled for strategic extraction were randomly assigned either to the test or to the control treatment. A lateral perforation was drilled on the root and either repaired with MTA/Biodentine or filled with gutta‐percha(control). Three months later, the teeth were extracted along with the coronal third of the alveolar bone and a portion of gingival tissue, while performing implant placement, and processed for histological analysis.
Results
Biodentine resulted in less extrusion into the periodontal environment. All the materials showed good biocompatibility. A new mineralized cementum‐like tissue incorporating periodontal fibres was visible in all cases treated with MTA. A small amount of new mineralized tissue was found in two Biodentine cases but not in control cases. Biodentine resulted in less damage to the periodontal ligament.
Conclusions
Bioactivity and biocompatibility of MTA were confirmed in human models. Biodentine proved to be biocompatible, but it seems not to induce cementum regeneration.
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