One-Pot Synthesis of Luminescent and Photothermal Carbon Boron-Nitride Quantum Dots Exhibiting Cell Damage Protective Effects.

Zero-dimensional boron nitride quantum dots (BNQDs) are arousing interest for their versatile optical, chemical, and biochemical properties. Introducing carbon contents in BNQDs nanostructures is a great challenge to modulate their physicochemical properties. Among the carbon moieties, phenolic groups have attracted attention for their biochemical properties and phenol-containing nanomaterials are showing great promise for biomedical applications. Herein, the first example of direct synthesis of water dispersible BNQDs exposing phenolic and carboxylic groups is presented. The carbon-BNQDs are prepared in a single-step by solvent-assisted reaction of urea with boronic reagents and are characterized by optical absorption, luminescence, Raman, Fourier transform infrared and NMR spectroscopy, X-ray photoelectron spectroscopy, dynamic light scattering, and atomic force microscopy. The carbon-BNQDs exhibit nanodimension, stability, high photothermal conversion efficiency, pH-responsive luminescence and Z-potential. The potential of the carbon-BNQDs to provide photothermal materials in solid by embedding in agarose substrate is successfully investigated. The carbon-BNQDs exhibit biocompatibility on colorectal adenocarcinoma cells (Caco-2) and protective effects from chemical and oxidative stress on Caco-2, osteosarcoma (MG-63), and microglial (HMC-3) cells. Amplicon mRNA-seq analyses for the expression of 56 genes involve in oxidative-stress and inflammation are performed to evaluate the molecular events responsible for the cell protective effects of the carbon-BNQDs.

Red light-triggerable nanohybrids of graphene oxide, gold nanoparticles and thermo-responsive polymers for combined photothermia and drug release effects.

The development of multifunctional nanohybrid systems for combined photo-induced hyperthermia and drug release is a challenging topic in the research of advanced materials for application in the biomedical field. Here, we report the first example of a three-component red-light-responsive nanosystem consisting of graphene oxide, gold nanoparticles and poly-N-isopropylacrylamide (GO-Au-PNM). The GO-Au-PNM nanostructures were characterized by spectroscopic techniques and atomic force microscopy. They exhibited photothermal conversion effects at various wavelengths, lower critical solution temperature (LCST) behaviour, and curcumin (Curc) loading capacity. The formation of GO-Au-PNM/Curc adducts and photothermally controlled drug release, triggered by red-light excitation (680 nm), were demonstrated using spectroscopic techniques. Drug-polymer interaction and drug-release mechanism were well supported by modelling simulation calculations. The cellular uptake of GO-Au-PNM/Curc was imaged by confocal laser scanning microscopy. In vitro experiments revealed the excellent biocompatibility of the GO-Au-PNM that did not affect the viability of human cells.

Evaluation of the Effects of Heteroaryl Ethylene Molecules in Combination with Antibiotics: A Preliminary Study on Control Strains.

The discovery of compounds with antibacterial activity is crucial in the ongoing battle against antibiotic resistance. We developed two QSAR models to design six novel heteroaryl drug candidates and assessed their antibacterial properties against nine ATCC strains, including Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and also Salmonella enterica and Escherichia coli, many of which belong to the ESKAPE group. We combined PB4, a previously tested compound from published studies, with GC-VI-70, a newly discovered compound, with the best cytotoxicity/MIC profile. By testing sub-MIC concentrations of PB4 with five antibiotics (linezolid, gentamycin, ampicillin, erythromycin, rifampin, and imipenem), we evaluated the combination's efficacy against the ATCC strains. To assess the compounds' cytotoxicity, we conducted a 24 h and 48 h 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on colorectal adenocarcinoma (CaCo-2) cells. We tested the antibiotics alone and in combination with PB4. Encouragingly, PB4 reduced the MIC values for GC-VI-70 and for the various clinically used antibiotics. However, it is essential to note that all the compounds studied in this research exhibited cytotoxic activity against cells. These findings highlight the potential of using these compounds in combination with antibiotics to enhance their effectiveness at lower concentrations while minimizing cytotoxic effects.

Impact of buffer composition on biochemical, morphological and mechanical parameters: A tare before dielectrophoretic cell separation and isolation.

Dielectrophoresis (DEP) represents an electrokinetic approach for discriminating and separating suspended cells based on their intrinsic dielectric characteristics without the need for labeling procedure. A good practice, beyond the physical and engineering components, is the selection of a buffer that does not hinder cellular and biochemical parameters as well as cell recovery. In the present work the impact of four buffers on biochemical, morphological, and mechanical parameters was evaluated in two different cancer cell lines (Caco-2 and K562). Specifically, MTT ([3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]) assay along with flow cytometry analysis were used to evaluate the occurring changes in terms of cell viability, morphology, and granulocyte stress formation, all factors directly influencing DEP sorting capability. Quantitative real-time PCR (qRT-PCR) was instead employed to evaluate the gene expression levels of interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), two well-known markers of inflammation and oxidative stress, respectively. An additional marker representing an index of cellular metabolic status, i.e. the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, was also evaluated. Among the four buffers considered, two resulted satisfactory in terms of cell viability and growth recovery (24 h), with no significant changes in cell morphology for up to 1 h in suspension. Of note, gene expression analysis showed that in both cell lines the apparently non-cytotoxic buffers significantly modulated IL-6, iNOS, and GAPDH markers, underlining the importance to deeply investigate the molecular and biochemical changes occurring during the analysis, even at apparently non-toxic conditions. The selection of a useful buffer for the separation and analysis of cells without labeling procedures, preserving cell status, represents a key factor for DEP analysis, giving the opportunity to further use cells for additional analysis.

PD-1, PD-L1 and cAMP immunohistochemical expressions are associated with worse oncological outcome in patients with bladder cancer.

PURPOSE: In this study, we aimed to identify prognostic factors of cancer mortality in patients who received radical cystectomy and to identify genomic alterations in a sub-cohort of patients with locally advanced (pT3-4) and/or positive lymph nodes bladder cancer (BC). METHODS: We collected 101 BC samples from 2010 to 2018 who previously received radical cystectomy. Immunohistochemical slides were evaluated for PPAR, cAMP, IMP3, Ki67, CDK4, POU5F1, Cyclin E and MDM2, p65, CD3, CD4, CD8, CD20, CD68, CD163, FOXP3, PD-1 and PD-L1 expression. We calculated a prognostic score (PS) based on the positivity to PD-1, PD-L1 and of cAMP (final score ranging from 0 to 3). DNA of each sample have been used for sequencing by NGS in a sub-cohort of 6 patients with locally advanced (pT3-4) and/or positive lymph nodes BC. RESULTS: PD-1 + (HR [hazard ratio] 2.59; p = 0.04), PD-L1+ (HR = 6.46; p < 0.01) and cAMP+ (HR 3.04; p = 0.02) were independent predictors of cancer-specific mortality (CSM). Increase of PS (score = 0 as reference) was associated with CSM, 0.81 (p = 0.80), 4.72 (p = 0.01) and 10.51 (p < 0.0) for PS 1, 2 and 3, respectively. ERBB2 was the gene most frequently mutated. CONCLUSION: BC exhibited heterogenous protein expression and variable genomic features. Identification of expression of PD-1, PD-L1 and cAMP could help in predicting oncological outcomes.

Label-Free Enrichment of Circulating Tumor Plasma Cells: Future Potential Applications of Dielectrophoresis in Multiple Myeloma.

In multiple myeloma (MM), circulating tumor plasma cells (CTPCs) are an emerging prognostic factor, offering a promising and minimally invasive means for longitudinal patient monitoring. Recent advances highlight the complex biology of plasma cell trafficking, highlighting the phenotypic and genetic signatures of intra- and extra-medullary MM onset, making CTPC enumeration and characterization a new frontier of precision medicine for MM patients, requiring novel technological platforms for their standardized and harmonized detection. Dielectrophoresis (DEP) is an emerging label-free cell manipulation technique to separate cancer cells from healthy cells in peripheral blood samples, based on phenotype and membrane capacitance that could be successfully tested to enumerate and isolate CTPCs. Herein, we summarize preclinical data on DEP development for CTPC detection, as well as their clinical and research potential.

Genomic Landscape Alterations in Primary Tumor and Matched Lymph Node Metastasis in Hormone-Naïve Prostate Cancer Patients.

BACKGROUND: Prostate cancer (PCa) is a disease with a wide range of clinical manifestations. Up to the present date, the genetic understanding of patients with favorable or unfavorable prognosis is gaining interest for giving the appropriate tailored treatment. We aimed to investigate genetic changes associated with lymph node metastasis in a cohort of hormone-naïve Pca patients. METHODS: We retrospectively analyzed data from 470 patients who underwent surgery for PCa between 2010 and 2020 at the Department of Urology, University of Catania. Inclusion criteria were patients with lymph node metastasis and patients with PCa with extra capsular extension (pT3) and negative lymph node metastasis. The final cohort consisted of 17 different patients (11 PCa with lymph node metastasis and 6 PCa without lymph node metastasis). Through the cBioPortal online tool, we analyzed gene alterations and their correlations with clinical factors. RESULTS: A total of 688 intronic, synonym and nonsynonym mutations were sequenced. The gene with the most sequenced mutations was ERBB4 (83 mutations, 12% of 688 total), while the ones with the lower percentage of mutations were AKT1, FGFR2 and MLH1 (1 mutation alone, 0.14%). CONCLUSION: In the present study we found mostly concordance concerning the ERBB4 mutation between both primary PCa samples and matched lymph node metastasis, underlining that the identification of alterations in the primary tumor is extremely important for cancer prognosis prediction.

Heteroaryl-Ethylenes as New Lead Compounds in the Fight against High Priority Bacterial Strains.

The widespread use of antibiotics has led to a gradual increase in drug-resistant bacterial infections, which severely weakens the clinical efficacy of antibacterial therapies. In recent decades, stilbenes aroused great interest because of their high bioavailability, as well as their manifold biological activity. Our research efforts are focused on synthetic heteroaromatic stilbene derivatives as they represent a potentially new type of antibiotic with a wide antibacterial spectrum. Herein, a preliminary molecular modeling study and a versatile synthetic scheme allowed us to define eight heteroaromatic stilbene derivatives with potential antimicrobial activity. In order to evaluate our compound's activity spectrum and antibacterial ability, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests have been performed on Gram-positive and Gram-negative ATCC strains. Compounds PB4, PB5, PB7, and PB8 showed the best values in terms of MIC and were also evaluated for MBC, which was found to be greater than MIC, confirming a bacteriostatic activity. For all compounds, we evaluated toxicity on colon-rectal adenocarcinoma cells tumor cells (CaCo2), once it was established that the whole selected set was more active than 5-Fluorouracil in reducing CaCo-2 cells viability. To the best of our knowledge, the biological assays have shown for these derivatives an excellent bacteriostatic activity, compared to similar molecular structures previously reported, thus paving the way for a new class of antibiotic compounds.

[Turn-over of non-tenured public health research personnel in an Italian public research institute (IRCCS).] / Il turn-over del personale con contratti di lavoro flessibili o borse di studio dedicato alla ricerca sanitaria in un IRCCS pubblico italiano.

BACKGROUND: The objective is to show variations in the number of non-tenured personnel (NTP) in a public health research centre (IRCCS) between 30th June 2016 and 31st December 2017. In this time interval, the issue of NTP was at the centre of governmental discussions. METHODS: Data collection was performed from CVs and scientific publications of NTP working at the Fondazione IRCCS Istituto Nazionale dei Tumori (INT). We compared the characteristics of NTP entering or leaving INT and those of NTP who remained in the considered time interval. RESULTS: NTP in INT counted 465 members of staff at 30th June 2016 and 472 at 31st December 2017. 75% of these works in the research. 26% of NTP left INT and their position resulted entirely substituted by other NTP. NTP staff who left are mainly aged under 40 and show fewer publications than those who stayed. Newly acquired NTP are younger and show a fewer number of publications compared to the personnel who left. CONCLUSIONS: 1 out of 4 NTP members of staff moved to a new job during a period in which the uncertain future of NTP research staff was under the spotlight. It appears that IRCCS are progressively being identified as suitable for hands-on, post university internships from which researchers would then choose to move, in search of a new job in public or private centres, with a consequent decline of IRCCS' role in health research.