A potential role of il-6/il-6r in the development and management of colon cancer

Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second greatest cause of cancer deaths. About 75% of all CRCs are sporadic cancers and arise following somatic mutations, while about 10% are hereditary cancers caused by germline mutations in specific genes. Several factors, such as growth factors, cytokines, and genetic or epigenetic alterations in specific oncogenes or tumor-suppressor genes, play a role during the adenoma–carcinoma sequence. Recent studies have reported an increase in interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) levels in the sera of patients affected by colon cancer that correlate with the tumor size, suggesting a potential role for IL-6 in colon cancer progression. IL-6 is a pleiotropic cytokine showing both pro-and anti-inflammatory roles. Two different types of IL-6 signaling are known. Classic IL-6 signaling involves the binding of IL-6 to its membrane receptor on the surfaces of target cells; alternatively, IL-6 binds to sIL-6R in a process called IL-6 trans-signaling. The activation of IL-6 transsignaling by metalloproteinases has been described during colon cancer progression and metastasis, involving a shift from membrane-bound interleukin-6 receptor (IL-6R) expression on the tumor cell surface toward the release of soluble IL-6R. In this review, we aim to shed light on the role of IL-6 signaling pathway alterations in sporadic colorectal cancer and the development of familial polyposis syndrome. Furthermore, we evaluate the possible roles of IL-6 and IL-6R as biomarkers useful in disease follow-up and as potential targets for therapy, such as monoclonal antibodies against IL-6 or IL-6R, or a food-based approach against IL-6

Preferential use of the perchlorate over the nitrate in the respiratory processes mediated by the Bacterium Azospira sp. OGA 24

Here we report the results obtained for a strain isolated from a polluted site and classified as Azospira sp. OGA 24. The capability of OGA 24 to utilize perchlorate and nitrate and the regulation of pathways were investigated by growth kinetic studies and analysis of messenger RNA (mRNA) expression of the genes of perchlorate reductase alpha subunit (pcrA), chlorite dismutase (cld), and periplasmic nitrate reductase large subunit (napA). In aerobic conditions and in a minimal medium containing 10 mM acetate as carbon source, 5.6 ± 0.34 mmol L-1 perchlorate or 9.7 ± 0.22 mmol L-1 nitrate were efficiently reduced during the growth with 10 mM of either perchlorate or nitrate. In anaerobiosis, napA was completely inhibited in the presence of perchlorate as the only electron acceptor, pcrA was barely detectable in nitrate-reducing conditions. The cell growth kinetics were in accordance with expression data, indicating a separation of nitrate and perchlorate respiration pathways. In the presence of both compounds, anaerobic nitrate consumption was reduced to 50% (4.9 ± 0.4 vs. 9.8 ± 0.15 mmol L-1 without perchlorate), while that of perchlorate was not affected (7.2 ± 0.5 vs. 6.9 ± 0.6 mmol L-1 without nitrate). Expression analysis confirmed the negative effect of perchlorate on nitrate respiration. Based on sequence analysis of the considered genes and 16S ribosomal gene (rDNA), the taxonomic position of Azospira sp. OGA 24 in the perchlorate respiring bacteria (PRB) group was further defined by classifying it in the oryzae species. The respiratory characteristics of OGA 24 strain make it very attractive in terms of potential applications in the bioremediation of environments exposed to perchlorate salts

Amine‐Functionalized Mesoporous Silica Adsorbent for CO2 Capture in Confined‐Fluidized Bed: Study of the Breakthrough Adsorption Curves as a Function of Several Operating Variables

Carbon capture, utilization, and storage (CCUS) is one of the key promising technologies that can reduce GHG emissions from those industries that generate CO2 as part of their production processes. Compared to other effective CO2 capture methods, the adsorption technique offers the possibility of reducing the costs of the process by setting solid sorbent with a high capacity of adsorption and easy regeneration and, also, controlling the performance of gas‐solid contactor. In this work, an amine‐functionalized mesoporous sorbent was used to capture CO2 emissions in a confined‐fluidized bed. The adoption of a confined environment allows the establishment of a homogeneous expansion regime for the sorbent and allows to improve the exchange of matter and heat between gas and solid phase. The results illustrate how the different concentration of the solution adopted during the functionalization affects the adsorption capacity. That, measured as mg of CO2 per g of sorbent, was determined by breakthrough curves from continuous adsorption tests using different concentrations of CO2 in air. Mesoporous silica functionalized with a concentration of 20% of APTES proves to be the best viable option in terms of cost and ease of preparation, low temperature of regeneration, and effective use for CO2 capture

Acute Dacryocystitis with Empyema of the Lacrimal Sac: Is Immediate Endoscopic Dacryocystorhinostomy Justified?

Objectives. To evaluate the efficacy of endoscopic dacryocystorhinostomy (Endo-DCR) in the treatment of acute dacryocystitis with lacrimal sac empyema (ADLSE). Design. Case series with chart review. Setting. Academic tertiary center. Patients. The study included 26 consecutive patients who underwent Endo-DCR for ADLSE between August 2005 and December 2013. Main Outcome Measures. The success of the procedure was defined as complete complaint relief and DCR patency. Data on the time from referral to surgery, postoperative complications, and revision surgery are also reported. Results. The present patient series included 4 males (15.4%) and 22 females (84.6%) (mean age, 66 years). The mean time between referral and surgery was 0.88 days and the mean follow-up time was 29 months. All patients showed immediate relief from symptoms, with no ADLSE recurrences. Complete success was achieved in 25 (96.2%) cases; the only failure was in a patient who had previously undergone radioiodine treatment. In this case, revision Endo-DCR was not successful. The only perioperative complication (3.8%) was epistaxis in a patient who required revision surgery under general anesthesia. The definitive success rate was 96.2% after primary and revision surgery. Conclusions. Endo-DCR enables rapid resolution of ADLSE with a very high success rate. Immediate surgery may reduce the risk of skin fistulization and/or orbital complications. DCR shrinkage and lacrimal obstruction are unlikely with Endo-DCR since the procedure is performed on an enlarged sac. The main advantage of Endo-DCR, compared with external DCR, is the absence of a skin incision in an inflamed and infected field

Isolation and Characterization of Multiple Forms of Glutamate-Aspartate Aminotransferase from Pig Heart

Abstract At least four different protein fractions provided with aspartate aminotransferase activity can be isolated from pig heart cytoplasm. No difference is detected in the sedimentation coefficient, immunodiffusion properties, and primary structure (as studied by quantitative amino acid analysis and peptide mapping of tryptic digests) of the three main fractions, called, respectively, α, β, and γ in their order of increasing anodic mobility on starch gel electrophoresis. The three main fractions differ significantly in specific activity, kinetics of recombination of the apoenzyme with the coenzyme, and behavior in 8 m urea. The most visible difference among them is in the way in which the coenzyme is bound to the enzyme protein. In the α and β fractions, pyridoxal phosphate is bound mostly in an "active" mode, characterized by absorption peaks at 362 or 430 mµ (depending upon the pH) and by the capacity to transaminate reversibly with the amino acid substrates. In the γ form, most of the coenzyme is bound in a nonactive mode, characterized by an absorption peak at 340 mµ and by the incapacity to react with amino acid substrates. Upon aging, the α and β fractions lose some activity, while a portion of their coenzyme becomes bound in the inactive mode. Even after these changes have occurred, the various fractions maintain their electrophoretic individuality, which is also preserved after resolution and after treatment with concentrated urea. Electrophoretic analyses carried out on a water extract of a single heart taken immediately after the death of the animal reveal the presence of the various subforms; this indicates either that the various subforms exist as such in the living cell or, if they are artifacts, that they must be formed very early in the preparation and under extremely mild conditions

Adsorption of the prototypical organic corrosion inhibitor benzotriazole on the Cu(100) surface

The interaction of benzotriazole (BTAH) with Cu(100) has been studied as a function of BTAH exposure in a joint experimental and theoretical effort. Scanning tunnelling microscopy (STM), X-ray photoelectron spectroscopy (XPS), high resolution electron energy loss spectroscopy (HREELS) and density functional theory (DFT) calculations have been combined to elucidate the structural and chemical characteristics of this system. BTAH is found to deprotonate upon adsorption on the copper surface and to adopt an orientation that depends on the molecular coverage. Benzotriazolate (BTA) species initially lie with their planes parallel to the substrate but, at a higher molecular coverage, a transition occurs to an upright adsorption geometry. Upon increasing the BTAH exposure, different phases of vertically aligned BTAs are observed with increasing molecular densities until a final, self-limiting monolayer is developed. Both theory and experiment agree in identifying CuBTA and Cu(BTA)2 metal-organic complexes as the fundamental building blocks of this monolayer. This work shows several similarities with the results of previous studies on the interaction of benzotriazole with other low Miller index copper surfaces, thereby ideally completing and concluding them. The overall emerging picture constitutes an important starting point for understanding the mechanism for protection of copper from corrosion

Diauxie and co-utilization of carbon sources can coexist during bacterial growth in nutritionally complex environments

It is commonly thought that when multiple carbon sources are available, bacteria metabolize them either sequentially (diauxic growth) or simultaneously (co-utilization). However, this view is mainly based on analyses in relatively simple laboratory settings. Here we show that a heterotrophic marine bacterium, Pseudoalteromonas haloplanktis, can use both strategies simultaneously when multiple possible nutrients are provided in the same growth experiment. The order of nutrient uptake is partially determined by the biomass yield that can be achieved when the same compounds are provided as single carbon sources. Using transcriptomics and time-resolved intracellular 1H-13C NMR, we reveal specific pathways for utilization of various amino acids. Finally, theoretical modelling indicates that this metabolic phenotype, combining diauxie and co-utilization of substrates, is compatible with a tight regulation that allows the modulation of assimilatory pathways

The anti-apoptotic effect of ASC-exosomes in an in vitro ALS model and their proteomic analysis

Stem cell therapy represents a promising approach in the treatment of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). The beneficial effect of stem cells is exerted by paracrine mediators, as exosomes, suggesting a possible potential use of these extracellular vesicles as non-cell based therapy. We demonstrated that exosomes isolated from adipose stem cells (ASC) display a neuroprotective role in an in vitro model of ALS. Moreover, the internalization of ASC-exosomes by the cells was shown and the molecules and the mechanisms by which exosomes could exert their beneficial effect were addressed. We performed for the first time a comprehensive proteomic analysis of exosomes derived from murine ASC. We identified a total of 189 proteins and the shotgun proteomics analysis revealed that the exosomal proteins are mainly involved in cell adhesion and negative regulation of the apoptotic process. We correlated the protein content to the anti-apoptotic effect of exosomes observing a downregulation of pro-apoptotic proteins Bax and cleaved caspase-3 and upregulation of anti-apoptotic protein Bcl-2 \u3b1, in an in vitro model of ALS after cell treatment with exosomes. Overall, this study shows the neuroprotective effect of ASC-exosomes after their internalization and their global protein profile, that could be useful to understand how exosomes act, demonstrating that they can be employed as therapy in neurodegenerative diseases