Expression of Calcitonin Gene-Related Peptide and Calcitonin Receptor-like Receptor in Colorectal Adenocarcinoma.

Colorectal cancer is one of the most widespread types of cancer that still causes many deaths worldwide. The development of new diagnostic and prognostic markers, as well as new therapeutic methods, is necessary. The calcitonin gene-related peptide (CGRP) neuropeptide alongside its receptor calcitonin receptor-like receptor (CRLR) could represent future biomarkers and a potential therapeutic target. Increased levels of CGRP have been demonstrated in thyroid, prostate, lung, and breast cancers and may also have a role in colorectal cancer. At the tumor level, it acts through different mechanisms, such as the angiogenesis, migration, and proliferation of tumor cells. The aim of this study was to measure the level of CGRP in colorectal cancer patients' serum by enzyme-linked immunosorbent assay (ELISA) and determine the level of CGRP and CRLR at the tumor level after histopathological (HP) and immunohistochemical (IHC) analysis, and then to correlate them with the TNM stage and with different tumoral characteristics. A total of 54 patients with newly diagnosed colorectal adenocarcinoma were evaluated. We showed that serum levels of CGRP, as well as CGRP and CRLR tumor level expression, correlate with the TNM stage, with local tumor extension, the presence of lymph node metastasis, and distant metastasis, and also with the tumor differentiation degree. CGRP is present in colorectal cancer from the incipient TNM stage, with levels increasing with the stage, and can be used as a diagnostic and prognostic marker and may also represent a potentially new therapeutic target.

Correlation of the Pro-Inflammatory Cytokines IL-1ß, IL-6, and TNF-α, Inflammatory Markers, and Tumor Markers with the Diagnosis and Prognosis of Colorectal Cancer.

Colorectal cancer (CRC) remains one of the most important global health problems, being in the top 3 neoplasms in terms of the number of cases worldwide. Although CRC develops predominantly from the adenoma-adenocarcinoma sequence through APC gene mutations, in recent years, studies have demonstrated the role of chronic inflammation in this neoplasia pathogenesis. Cytokines are important components of chronic inflammation, being some of the host regulators in response to inflammation. The pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α are involved in tumor cell proliferation, angiogenesis, and metastasis and seem to strengthen each other's mode of action, these being stimulated by the same mediators. In our study, we collected data on 68 patients with CRC and 20 healthy patients from the Gastroenterology Department of Craiova County Emergency Clinical Hospital, who were assessed between January 2022 and February 2023. The main purpose of this study was to investigate the correlation between increased plasma levels of the cytokines and the extent of the tumor, lymph nodes, and metastasis-(TNM stage), as well as the patients' prognoses. We also compared the plasma levels of cytokines and acute inflammatory markers, namely, the erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and fibrinogen, along with the tumor markers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 19.9), in CRC patients. We showed that all the pro-inflammatory cytokines studied had higher levels in patients with CRC in comparison with the control group. We also showed that the acute inflammatory markers of erythrocyte sedimentation rate, C-reactive protein, and fibrinogen, and the tumor markers of CEA and CA 19.9 can be useful in diagnosis and prognosis in patients with CRC. Considering the association between pro-inflammatory cytokines and CRC, the development of new targeted therapies against IL-1ß, IL-6, and TNF-α can improve patient care and the CRC survival rate.

Surface Chemistry of Gold Nanoparticles Produced by Laser Ablation in Pure and Saline Water.

Pulsed laser ablation in liquid (PLAL) is a powerful method for producing nanoparticle colloids with a long-term stability despite the absence of stabilizing organic agents. The colloid stability involves different reactivities and chemical equilibria with complex ionic-specific effects at the nanoparticle/solvent interface which must be strongly influenced by their chemical composition. In this work, the surface composition of PLAL-produced gold nanoparticles in alkaline and saline (NaBr) water is investigated by X-ray photoelectron spectroscopy on free-flying nanoparticles, exempt from any substrate or radiation damage artifact. The Au 4f photoelectron spectra with a depth profiling investigation are used to evaluate the degree of nanoparticle surface oxidation. In alkaline water, the results preclude any surface oxidation contrary to the case of nanoparticles produced in NaBr solution. In addition, the analysis of Br 3d core-level photoelectron spectra agrees with a clear signature of Br on the nanoparticle surface, which is confirmed by a specific valence band feature. This experimental study is supported by DFT calculations, evaluating the energy balance of halide adsorption on different configurations of gold surfaces including oxidation or adsorbed salts.

Assessing the Surface Oxidation State of Free-Standing Gold Nanoparticles Produced by Laser Ablation.

The surface chemistry of gold nanoparticles produced by the pulsed laser ablation in liquids method is investigated by X-ray photoelectron spectroscopy (XPS). The presence of surface oxide expected on these systems is investigated using synchrotron radiation in conditions close to their original state in solvent but free from substrate or solvent effects which could affect the interpretation of spectroscopic observations. For that purpose we performed the experiment on a controlled free-standing nanoparticle beam produced by combination of an atomizer and an aerodynamic lens system. These results are compared with those obtained by the standard situation of deposited nanoparticles on silicon substrate. An accurate analysis based on Bayesian statistics concludes that the existence of oxide in the free-standing conditions cannot be solely confirmed by the recorded core-level 4f spectra. If present, our data indicate an upper limit of 2.15 ± 0.68% of oxide. However, a higher credence to the hypothesis of its existence is brought by the structureless valence profile of the free-standing beam. Moreover, the cross-comparison with the deposited nanoparticles case clearly evidences an important misleading substrate effect. Experiment with free-standing nanoparticles is then demonstrated to be the right way to further investigate oxidation states on Au nanoparticles.

Stability of blood potassium: effects of duration, temperature and transport during 10 hours storage of human whole blood in serum and plasma.

To comply with the pre-analytical requirements of ISO EN 15189, we investigated the stability of potassium, a very critical and sensitive analyte. We took into count effects of duration, temperature and transport after 10 hours storage of human whole blood in serum and plasma. Blood of 12 healthy subjects was analyzed after 4, 6, 8 and 10 hours of storage. Three study groups were designed: samples stored in laboratory at room temperature, transported by car during 4 hours at a temperature of 21±1̊C, with or without previous thermal shock (20 min at 4±1 ÌŠC) before transportation. Variations in concentration were expressed as mean bias from baseline using the analytical change limit (ACL) and the reference change value (RCV). Using RCV, we considered that potassium was biologically stable during 10 hours whatever our study groups. Considering ACL, potassium in serum was not stable after the thermal shock. We conclude that whole blood in lithium-heparin tubes may be used for routine potassium analysis even if long car transportation and previous thermal shock is involved. It confirms that potassium analysis can be still performed in locations distant from a medical laboratory.

X-ray Photoelectron Spectroscopy of Isolated Nanoparticles.

X-ray photoelectron spectroscopy (XPS) is a very efficient and still progressing surface analysis technique. However, when applied to nano-objects, this technique faces drawbacks due to interactions with the substrate and sample charging effects. We present a new experimental approach to XPS based on coupling soft X-ray synchrotron radiation with an in-vacuum beam of free nanoparticles, focused by an aerodynamic lens system. The structure of the Si/SiO2 interface was probed without any substrate interaction or charging effects for silicon nanocrystals previously oxidized in ambient air. Complete characterization of the surface was obtained. The Si 2p core level spectrum reveals a nonabrupt interface.

A multi purpose source chamber at the PLEIADES beamline at SOLEIL for spectroscopic studies of isolated species: cold molecules, clusters, and nanoparticles.

This paper describes the philosophy and design goals regarding the construction of a versatile sample environment: a source capable of producing beams of atoms, molecules, clusters, and nanoparticles in view of studying their interaction with short wavelength (vacuum ultraviolet and x-ray) synchrotron radiation. In the design, specific care has been taken of (a) the use standard components, (b) ensuring modularity, i.e., that swiftly switching between different experimental configurations was possible. To demonstrate the efficiency of the design, proof-of-principle experiments have been conducted by recording x-ray absorption and photoelectron spectra from isolated nanoparticles (SiO2) and free mixed clusters (Ar/Xe). The results from those experiments are showcased and briefly discussed.

Improvement of myocardial contractility in a porcine model of chronic ischemia using a combined transmyocardial revascularization and gene therapy approach.

OBJECTIVES: The purpose of this study was to investigate whether a novel fibroblast growth factor-2 gene formulation, providing a localized and sustained availability of the adenoviral vector from a collagen-based matrix, in combination with CO 2 transmyocardial laser revascularization would lead to an enhanced angiogenic response and improved myocardial function. METHODS: Fibroblast growth factor-2 gene was delivered by means of an adenoviral vector (adenoviral fibroblast growth factor-2) formulated in a collagen-based matrix. The ischemic areas of 33 animals were then treated. Group 1 was treated with CO 2 transmyocardial laser revascularization; group 2 was treated with intramyocardial injections of adenoviral fibroblast growth factor-2 in a collagen-based matrix; group 3 had a combination treatment of matrix adenoviral fibroblast growth factor-2 and CO 2 transmyocardial laser revascularization; and group 4 received injections with saline-formulated adenoviral fibroblast growth factor-2. Baseline left ventricular function was assessed by echocardiography and cine magnetic resonance imaging. Studies were repeated 6 weeks after treatment. Vascular development was assessed using anti-alpha-actin immunohistochemistry. RESULTS: Matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularization-treated areas had a 105% increase in arteriolar development versus either treatment alone ( P < .05) and a 390% increase compared with saline-formulated adenoviral fibroblast growth factor-2 treatment alone ( P < .05). Contractility was significantly improved in matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularization-treated areas as measured by myocardial wall thickening. This functional improvement was confirmed by cine magnetic resonance imaging, in which a 90% increase in the contractility of the treated segments was demonstrated after matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularation. The other treatments provided significantly less restoration of myocardial function. CONCLUSIONS: The increase in angiogenesis as a result of matrix adenoviral fibroblast growth factor-2 gene therapy in combination with CO 2 transmyocardial laser revascularization is greater than that seen in either therapy alone. A concomitant improvement in myocardial function was seen as a result of this angiogenic response.

What is the optimal channel density for transmyocardial laser revascularization?

BACKGROUND: Transmyocardial laser revascularization (TMR) has demonstrated reproducible relief of angina in patients with end-stage coronary disease. However, the optimum dose or channel density has not been elucidated. METHODS: Using a porcine model of chronic myocardial ischemia, 14 animals were treated with CO2 TMR and randomized as follows: group 1 was 1 channel per 2 cm2; group 2 was 1 channel per 1 cm2; and group 3 was 2 channels per 1 cm2. Left ventricular myocardial viability and function were assessed by magnetic resonance imaging (MRI) and echocardiography pretreatment, and repeated 6 weeks later. RESULTS: The MRI assessment of group 1 (1 channel/2 cm2) and group 2 (1 channel/cm2) demonstrated similar improvement in segmental contractility posttreatment of 12.11% +/- 5.15% and 12.47% +/- 9.51%, respectively. In contrast, group 3 (2 channels/cm2) showed significantly worse segmental contractility posttreatment: -18.52% +/- 7.16% (p = 0.01). Echocardiographic imaging revealed significant improvements in wall thickening in the ischemic zone for group 1 at 0.91 +/- 0.07 cm pretreatment versus 1.30 +/- 0.09 cm posttreatment, (p = 0.01); and for group 2 at 0.93 +/- 0.11 cm versus 1.42 +/- 0.18 cm, (p = 0.01). No significant improvement in wall thickening was seen in group 3 (0.84 +/- 0.06 cm versus 0.88 +/- 0.09 cm, p = n.s.). CONCLUSIONS: These data corroborate the empiric finding of an effective therapeutic dose range for TMR, 1 channel per 1 to 2 cm2. These results also demonstrate a detrimental effect when channel density is increased above the clinical standard of 1 channel per cm2 to a density of 2 channels per 1 cm2.

HIV type 1 and cytomegalovirus coinfection in the female genital tract.

The relationship between human immunodeficiency virus (HIV) type 1 and human cytomegalovirus (CMV) was studied in blood, saliva, and cervicovaginal lavage (CVL) specimens from 33 HIV-1-infected women. An association between HIV-1 RNA and CMV DNA was found in the CVL specimens, which also were tested for cytokine levels. Women with detectable CMV DNA in CVL specimens were more likely to have higher interleukin (IL)-1 beta and IL-8 levels than were women with undetectable CMV DNA in CVL specimens. More than 1 strain of CMV was detected in specimens from 2 patients. These results suggest mechanisms by which CMV coinfection could affect HIV-1 disease progression.

Analysis and characterization of antiviral drug-resistant cytomegalovirus isolates from solid organ transplant recipients.

The development of cytomegalovirus (CMV) disease and subsequent emergence of drug-resistant strains was examined in a large group of solid organ transplant recipients; drug-resistant CMV was detected in a total of 30 transplant recipients (20 lung, 5 kidney, 4 heart, and 1 liver). Drug resistance was confirmed both phenotypically and genotypically. The sequences of drug-resistant CMV strains from the same patient differed from drug-susceptible baseline sequences only at single sites previously confirmed to confer drug resistance. At least 1 isolate from each patient had a mutation in the UL97 phosphotransferase coding sequence. Mutations in the DNA polymerase gene were found in 6 of 38 sequenced strains. Lung transplant recipients had the highest incidence of drug-resistant virus: of the 30 patients, 28 were CMV-seronegative transplant recipients of CMV-seropositive organs, which strongly supports the premise that drug resistance is most prevalent in that transplant population.