Reprogramming the melanoma and immunosuppressive myeloid cells with esomeprazole-loaded PLGA nanoparticles.

Proton pump inhibitors have been explored for potentiating cancer therapies via reverting the tumor acidity and promoting the activation of anti-tumor immune responses. To regulate the intracellular pH of melanoma and immunosuppressive myeloid cells, we developed poly(L-lactide-co-glycolide) nanoparticles loaded with esomeprazole (ESO-NPs). The effect of ESO-NPs on melanoma cells was observed as alkalinization and reduction of melanin content accompanied by a decrease of microphthalmia-associated transcription factor (MITF), poliovirus receptor (PVR), and programmed death ligand 1 (PD-L1) immune checkpoint expression.

Footprint of sustained poleward warm water flow within East Antarctic submarine canyons.

The intrusion of relatively warm water onto the continental shelf is widely recognized as a threat to Antarctic ice shelves and glaciers grounded below sea level, as enhanced ocean heat increases their basal melt. While the circulation of warm water has been documented on the East Antarctic continental shelf, the modes of warm water transport from the deep ocean onto the shelf are still uncertain. This makes predicting the future responses of major East Antarctic marine-grounded glaciers, such as Totten and Ninnis glaciers, particularly challenging.

Development of an AAV-CRISPR-Cas9-based treatment for dominant cone-rod dystrophy 6.

Cone-rod dystrophy 6 (CORD6) is caused by gain-of-function mutations in the gene, which encodes retinal guanylate cyclase-1 (RetGC1). There are currently no treatments available for this autosomal dominant disease, which is characterized by severe, early-onset visual impairment. The purpose of our study was to develop an adeno-associated virus (AAV)-CRISPR-Cas9-based approach referred to as "ablate and replace" and evaluate its therapeutic potential in mouse models of CORD6.

Development of a Molecular Blood-Based Immune Signature Classifier as Biomarker for Risks Assessment in Lung Cancer Screening.

Background: Low-dose CT (LDCT) screening trials have shown that lung cancer early detection saves lives. However, a better stratification of the screening population is still needed. In this respect, we generated and prospectively validated a plasma miRNA signature classifier (MSC) able to categorize screening participants according to lung cancer risk.

Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer.

In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments.

Integrated transcriptional-phenotypic analysis captures systemic immunomodulation following antiangiogenic therapy in renal cell carcinoma patients.

Background: The combination of immune checkpoint blockade (ICB) with standard therapies is becoming a common approach for overcoming resistance to cancer immunotherapy in most human malignancies including metastatic renal cell carcinoma (mRCC). In this regard, insights into the immunomodulatory properties of antiangiogenic agents may help designing multidrug schedules based on specific immune synergisms.

Methods: We used orthogonal transcriptomic and phenotyping platforms combined with functional analytic pipelines to elucidate the immunomodulatory effect of the antiangiogenic agent pazopanib in mRCC patients.

Nutritional status in post SARS-Cov2 rehabilitation patients.

Background & Aims: After prolonged hospitalization, the assessment of nutritional status and the identification of adequate nutritional support is of paramount importance. In this observational study, we aimed at assessing the presence of a malnutrition condition in SARS-Cov2 patients after the acute phase and the effects of a multidisciplinary rehabilitation program on nutritional and functional status.

Methods: We recruited 48 patients (26 males/22 females) admitted to our Rehabilitation Unit after discharge from acute Covid Hospitals in northern Italy with negative swab for SARS-Cov2.

Back to simplicity: a four-marker blood cell score to quantify prognostically relevant myeloid cells in melanoma patients.

Background: Myeloid-derived suppressor cells (MDSC), a cornerstone of cancer-related immunosuppression, influence response to therapy and disease outcomes in melanoma patients. Nevertheless, their quantification is far from being integrated into routine clinical practice mostly because of the complex and still evolving phenotypic signatures applied to define the cell subsets. Here, we used a multistep downsizing process to verify whether a core of few markers could be sufficient to capture the prognostic potential of myeloid cells in peripheral blood mononuclear cells (PBMC) of metastatic melanoma patients.

Salt-tolerance induced by leaf spraying with HO in sunflower is related to the ion homeostasis balance and reduction of oxidative damage.

Salinity is still one of the main factors that limit the growth and production of crops. However, currently, hydrogen peroxide (HO) priming has become a promising technique to alleviate the deleterious effects caused by salt. Therefore, this study aimed to test different leaf spraying strategies with HO for acclimation of sunflower plants to salt stress, identifying the main physiological and biochemical changes involved in this process.

Natural-Killer-Derived Extracellular Vesicles: Immune Sensors and Interactors.

Natural killer (NK) cells contribute to immunosurveillance and first-line defense in the control of tumor growth and metastasis diffusion. NK-cell-derived extracellular vesicles (NKEVs) are constitutively secreted and biologically active. They reflect the protein and genetic repertoire of originating cells, and exert antitumor activity and .

Sugar and iron: Toward understanding the antibacterial effect of ciclopirox in Escherichia coli.

New antibiotics are needed against antibiotic-resistant gram-negative bacteria. The repurposed antifungal drug, ciclopirox, equally blocks antibiotic-susceptible or multidrug-resistant Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae clinical isolates, indicating that it is not affected by existing resistance mechanisms. Toward understanding how ciclopirox blocks growth, we screened E.

Circulating mir-320a promotes immunosuppressive macrophages M2 phenotype associated with lung cancer risk.

miRNAs play a central role in the complex signaling network of cancer cells with the tumor microenvironment. Little is known on the origin of circulating miRNAs and their relationship with the tumor microenvironment in lung cancer. Here, we focused on the cellular source and relative contribution of different cell types to circulating miRNAs composing our risk classifier of lung cancer using in vitro/in vivo models and clinical samples.

Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma.

The accrual of myeloid-derived suppressor cells (MDSCs) represents a major obstacle to effective immunotherapy in cancer patients, but the mechanisms underlying this process in the human setting remain elusive. Here, we describe a set of microRNAs (miR-146a, miR-155, miR-125b, miR-100, let-7e, miR-125a, miR-146b, miR-99b) that are associated with MDSCs and resistance to treatment with immune checkpoint inhibitors in melanoma patients. The miRs were identified by transcriptional analyses as being responsible for the conversion of monocytes into MDSCs (CD14+HLA-DRneg cells) mediated by melanoma extracellular vesicles (EVs) and were shown to recreate MDSC features upon transfection.

Antioxidant and antimicrobial properties of Casteanea sativa Miller chestnut honey produced on Mount Etna (Sicily).

The aim of this study was the evaluation of antibacterial and antioxidant properties of Monofloral Etna Castanea sativa Miller honeys. Escherichia coli ATCC 25,922, Pseudomonas aeruginosa ATCC 27,853, Enterococcus faecalis ATCC 29,211 and Staphylococcus aureus ATCC 29,213 were investigated for their susceptibilities to two different honeys. Antioxidant activity was evaluated by ORAC, NO scavenger assays, FRAP and DPPH.

Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy.

Purpose: We assessed the presence of salivary cytokines, their modulation during chemoradiation therapy (CTRT), and their association with oral mucositis severity in patients with head and neck cancer (HNC).

Methods And Materials: The present prospective observational study enrolled 55 patients with locally advanced HNC requiring CTRT. We also studied 10 healthy volunteers and 10 patients with other cancers.

Caspase-3 activation in human melanoma A375 cell line by a novel selective sigma-2 agonist.

Two novel 8-azabicyclo[3.2.1]octan-3-ol derivatives, 11a and 11b, with high affinity for sigma-2 receptors and a very good sigma-1/sigma-2 selectivity ratio were synthesized.

Effect of sugar addition on glass transition temperatures of cassava starch with low to intermediate moisture contents.

This work studies how sucrose (S) addition modifies the thermal properties of cassava starch (CS). Neat CS and CS-S blends with 4, 6 and 8% sugar contents (CS-S-4%, CS-S-6% and CS-S-8%) were prepared and analyzed by differential scanning calorimetry (DSC) and dynamic mechanical thermal analysis (DMTA), in a wide range of moisture levels (2-20%). In equilibrated samples with moisture contents lower than 10%, twoendothermic steps were observed during first DSC heating scans and two corresponding relaxation maxima in tan δ were detected by DMTA.

TNF-Related Apoptosis-Inducing Ligand (TRAIL)-Armed Exosomes Deliver Proapoptotic Signals to Tumor Site.

Purpose: Exosomes deliver signals to target cells and could thus be exploited as an innovative therapeutic tool. We investigated the ability of membrane TRAIL-armed exosomes to deliver proapoptotic signals to cancer cells and mediate growth inhibition in different tumor models.

Experimental Methods And Results: K562 cells, transduced with lentiviral human membrane TRAIL, were used for the production of TRAIL(+) exosomes, which were studied by nanoparticle tracking analysis, cytofluorimetry, immunoelectronmicroscopy, Western blot, and ELISA.

Parasites in the mangrove oyster Crassostrea rhizophorae cultivated in the estuary of the Graciosa River in Taperoá, Bahia.

In this work, parasites associated with the mangrove oyster Crassostrea rhizophorae were studied at a cultivation unit in the estuary of the Graciosa River in Taperoá, Bahia. On a monthly basis, between April 2011 and March 2012, 20 oysters were collected, measured and fixed in 10% formaldehyde. In order to identify the parasites, routine histological techniques were used.

DSC investigation of the effect of the new sigma ligand PPCC on DMPC lipid membrane.

The new sigma ligand cis-(±)-methyl (1R,2S/1S,2R)-2-[(4-hydroxy-4-phenylpiperidin-1-yl) methyl]-1-(4-methylphenyl) cyclopropanecarboxylate [(±)-PPCC] is a promising tool for the treatment of various diseases. With the aim to investigate the absorption of (±)-PPCC by the cell membranes, in this study we evaluated the influence on thermotropic behavior of membrane model exerted by PPCC both as free base or as oxalic salt. To fulfill this purpose differential scanning calorimetry was used.

Glass transitions and physical aging of cassava starch - corn oil blends.

Glass transition temperatures and physical aging of amorphous cassava starch and their blends with corn oil were assessed by differential scanning calorimetry (DSC). Two enthalpic relaxation endotherms, well separated in temperature values, were exhibited by neat amorphous cassava starch with 10.6% moisture content, evidencing two amorphous regions within the starch with different degrees of mobility.

HNF4α contributes to glucose formation in aged rat hepatocytes.

Aging-dependent physiological conditions are attributed to parenchymal structural changes to cellular functions in aged organisms. Compared to the young animals, the primary hepatocytes from old rats showed a higher glucose output and a higher expression of the key gluconeogenesis-regulating enzyme, phosphoenol pyruvate carboxykinase (PEPCK). The primary hepatocytes from old rats showed a higher glucose output and a higher expression of the key gluconeogenesis-regulating enzyme, phosphoenol pyruvate carboxykinase (PEPCK), compared with those from the young animals.

Anti-plasticization of cassava starch by complexing fatty acids.

The effect of adding 1-8% amylose complexing fatty acids (CFA), such as linoleic and oleic acids, on the glass transition temperature (Tg) of cassava starch (CS) with moisture content varying from 5 to 35% (dry basis) was studied. The main relaxation temperature (Tα), associated with the glass transition temperature of the samples (Tg), was determined by dynamic-mechanical-thermal analysis. The plasticizing behavior of water in the blends was evidenced by a decrease of Tα values with moisture content.