Real-World Treatment Outcomes of an Artificial Tear Containing Arabinogalactan, Hyaluronic Acid and Trehalose Among Subjects with Dry Eye.

Purpose: To assess the efficacy, adherence, and tolerability of a new artificial tear based on arabinogalactan, hyaluronic acid, and trehalose in a population with dry eye disease (DED).

Methods: A retrospective, real-world, post-marketing study identified 96 adult patients (aged 18-80 years) with signs and symptoms of dry eye. These patients received fixed combination therapy with eye drops containing arabinogalactan, hyaluronic acid, and trehalose at various dosing schedules.

REThinking the role of the RET oncogene in breast cancer.

The REarranged during Transfection (RET) receptor tyrosine kinase plays a crucial role in the development of various anatomical structures during embryogenesis and it is involved in many physiological cellular processes. This protein is also associated with the initiation of various cancer types, such as thyroid cancer, non-small cell lung cancer, and multiple endocrine neoplasms. In breast cancer, and especially in the estrogen receptor-positive (ER+) subtype, the activity of RET is of notable importance.

CD40/CD40L expression and its prognostic value in cervical cancer.

CD40, a member of the tumor necrosis factor receptor (TNFR) family, is known to be involved in immune system regulation, acting as a costimulatory molecule, and in antitumor responses against cancer cells. It is a protein that is expressed in different types of cells, including immune cells and cancer cells (e.g.

More Than Meets the Eye: A Case of Breast Cancer Switching from Being Luminal-Androgen-Receptor-Positive to Being Hormone-Receptor-Positive.

Triple-negative breast cancer (TNBC) represents about 15% of all breast cancers and is usually characterized by aggressive clinical behavior and a poor prognosis. Four TNBC subgroups have been previously defined with different molecular profiles: (i) luminal androgen receptor (LAR), (ii) mesenchymal (MES), (iii) basal-like immunosuppressed (BLIS) and (iv) basal-like immune-activated (BLIA). Among these, LAR is characterized by the expression of the androgen receptor (AR), and exhibits genomic characteristics that resemble luminal breast cancers, with a still undefined prognosis and clinical behavior.

Chiral isotopic fractionation in lemon essential oil: A tool for authenticity assessment?

The present research aimed to retrieve key information about the genuineness of Sicilian lemon essential oils by evaluating simultaneously the chiral and isotopic data of target terpene components. With respect to previous literature references, where chiral recognition and isotope discrimination were performed by distinct gas chromatographic methods, this study aimed to develop a single analytical approach. To overcome limitations associated to monodimensional gas chromatographic approaches, an enantio‑selective multidimensional gas chromatographic approach coupled to isotopic ratio mass spectrometry and to parallel single quadrupole detection (Es-MDGC-C-IRMS/qMS) was developed.

Preparative three-dimensional GC and nuclear magnetic resonance for the isolation and identification of two sesquiterpene ethers from Dictyota Dichotoma.

Separation science plays a crucial role in the isolation of novel compounds contained in complex matrices. Yet their rationale employment needs preliminary structure elucidation, which usually requires sufficient aliquots of grade substances to characterize the molecule by nuclear magnetic resonance experiments. In this study, two peculiar oxa-tricycloundecane ethers were isolated by means of preparative multidimensional gas chromatography from the brown alga species Dictyota dichotoma (Huds.

Distributed dynamic strain sensing of very long period and long period events on telecom fiber-optic cables at Vulcano, Italy.

Volcano-seismic signals can help for volcanic hazard estimation and eruption forecasting. However, the underlying mechanism for their low frequency components is still a matter of debate. Here, we show signatures of dynamic strain records from Distributed Acoustic Sensing in the low frequencies of volcanic signals at Vulcano Island, Italy.

Simultaneous evaluation of the enantiomeric and carbon isotopic ratios of Cannabis sativa L. essential oils by multidimensional gas chromatography.

Recent times have witnessed an upsurge of interest in hemp and hemp-derived products, as driven by the scientific findings specific to the pharmacological properties of Cannabis sativa L. and its constituents. There has been evidence that the terpene profile, along with the cannabinoid content, produces in humans the effects associated with different strains, beyond fragrance perception.

Cadmium and lipid balance in outdoor workers exposed to urban stressor.

The aim of our study was to evaluate the association between levels of blood and urinary cadmium and lipid balance in a group of outdoor workers. The study was conducted on a group of 146 individuals (average age 45,1 ± 8,5). Blood and urinary samples were collected for the detection of total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, blood cadmium and urinary cadmium.

Overcoming the lack of reliability associated to monodimensional gas chromatography coupled to isotopic ratio mass spectrometry data by heart-cut two-dimensional gas chromatography.

The use of IRMS as a GC detector has a history going back decades, however the critical issue of wrong δC measurements resulting from impure peaks has been often underestimated. To this regard, multidimensional separation techniques are effective tools to improve the reliability of the data, with respect to those obtained after monodimensional analysis. The present research aims to draw attention to one critical issue, related to the reliability of the δC data obtained by means of monodimensional GC-C-IRMS.

Heme catabolism by tumor-associated macrophages controls metastasis formation.

Although the pathological significance of tumor-associated macrophage (TAM) heterogeneity is still poorly understood, TAM reprogramming is viewed as a promising anticancer therapy. Here we show that a distinct subset of TAMs (F4/80CD115C3aRCD88), endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), plays a critical role in shaping a prometastatic tumor microenvironment favoring immunosuppression, angiogenesis and epithelial-to-mesenchymal transition. This population originates from F4/80HO-1 bone marrow (BM) precursors, accumulates in the blood of tumor bearers and preferentially localizes at the invasive margin through a mechanism dependent on the activation of Nrf2 and coordinated by the NF-κB1-CSF1R-C3aR axis.

Much More Than IL-17A: Cytokines of the IL-17 Family Between Microbiota and Cancer.

The interleukin-(IL-)17 family of cytokines is composed of six members named IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F. IL-17A is the prototype of this family, and it was the first to be discovered and targeted in the clinic. IL-17A is essential for modulating the interplay between commensal microbes and epithelial cells at our borders (i.

Arabinogalactan and hyaluronic acid in ophthalmic solution: Experimental effect on xanthine oxidoreductase complex as key player in ocular inflammation (in vitro study).

Dry eye syndrome is a common disease associated to eyes inflammation, irritation and tear film instability. The enzymatic complex of xanthine oxidoreductase (XOR) is involved in the generation of reactive oxygen species (ROS) and uric acid that, in the end, can cause reperfusion injuries, irritation and pathological conditions. Furthermore, in the eye, it has been proposed that oxygen free radicals might play a significant role in retinal ischemic damage.

A Bispecific Antibody to Link a TRAIL-Based Antitumor Approach to Immunotherapy.

T-cell-based immunotherapy strategies have profoundly improved the clinical management of several solid tumors and hematological malignancies. A recently developed and promising immunotherapy approach is to redirect polyclonal MHC-unrestricted T lymphocytes toward cancer cells by bispecific antibodies (bsAbs) that engage the CD3 complex and a tumor-associated antigen (TAA). The TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) is an attractive immunotherapy target, frequently expressed by neoplastic cells, that we decided to exploit as a TAA.

Targeting Immune-Related Biological Processes in Solid Tumors: We do Need Biomarkers.

Immunotherapy has become the standard-of-care in many solid tumors. Despite the significant recent achievements in the diagnosis and treatment of cancer, several issues related to patients' selection for immunotherapy remain unsolved. Multiple lines of evidence suggest that, in this setting, the vision of a single biomarker is somewhat naïve and imprecise, given that immunotherapy does not follow the rules that we have experienced in the past for targeted therapies.

Patients Selection for Immunotherapy in Solid Tumors: Overcome the Naïve Vision of a Single Biomarker.

Immunotherapy, and in particular immune-checkpoints blockade therapy (ICB), represents a new pillar in cancer therapy. Antibodies targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and Programmed Death 1 (PD-1)/Programmed Death Ligand-1 (PD-L1) demonstrated a relevant clinical value in a large number of solid tumors, leading to an improvement of progression free survival and overall survival in comparison to standard chemotherapy. However, across different solid malignancies, the immune-checkpoints inhibitors efficacy is limited to a relative small number of patients and, for this reason, the identification of positive or negative predictive biomarkers represents an urgent need.

Collection and identification of an unknown component from Eugenia uniflora essential oil exploiting a multidimensional preparative three-GC system employing apolar, mid-polar and ionic liquid stationary phases.

The present research deals with the collection and structural elucidation of an unknown component, accounting for about 35% of the essential oil obtained upon distillation of the leaves of Eugenia uniflora L., harvested during summer (January, 2017) in Paraná State (Southern Brazil). A multidimensional gas chromatographic preparative system, based on the coupling of three GC systems equipped with apolar, PEG and ionic liquid-based stationary phases, was successfully applied for the isolation of the chromatographic band relative to the unknown molecule.

An actionable axis linking NFATc2 to EZH2 controls the EMT-like program of melanoma cells.

Discovery of new actionable targets and functional networks in melanoma is an urgent need as only a fraction of metastatic patients achieves durable clinical benefit by targeted therapy or immunotherapy approaches. Here we show that NFATc2 expression is associated with an EMT-like transcriptional program and with an invasive melanoma phenotype, as shown by analysis of melanoma cell lines at the mRNA and protein levels, interrogation of the TCGA melanoma dataset and characterization of melanoma lesions by immunohistochemistry. Gene silencing or pharmacological inhibition of NFATc2 downregulated EMT-related genes and AXL, and suppressed c-Myc, FOXM1, and EZH2.

The non-small cell lung cancer immune landscape: emerging complexity, prognostic relevance and prospective significance in the context of immunotherapy.

Immunotherapy of non-small cell lung cancer (NSCLC), by immune checkpoint inhibitors, has profoundly improved the clinical management of advanced disease. However, only a fraction of patients respond and no effective predictive factors have been defined. Here, we discuss the prospects for identification of such predictors of response to immunotherapy, by fostering an in-depth analysis of the immune landscape of NSCLC.

Early Effector T Lymphocytes Coexpress Multiple Inhibitory Receptors in Primary Non-Small Cell Lung Cancer.

Clinical efficacy of PD-1/PD-L1 targeting relies upon the reactivation of tumor-specific but functionally impaired PD-1 T cells present before therapy. Thus, analyzing early-stage primary tumors may reveal the presence of T cells that are not yet functionally impaired. In this study, we report that activated (HLA-DR) T cells with an effector memory (T) profile are enriched in such lesions.

Primary cross-resistance to BRAFV600E-, MEK1/2- and PI3K/mTOR-specific inhibitors in BRAF-mutant melanoma cells counteracted by dual pathway blockade.

Intrinsic cross-resistance to inhibition of different signaling pathways may hamper development of combinatorial treatments in melanoma, but the relative frequency of this phenotype and the strategies to overcome this hurdle remain poorly understood. Among 49 BRAF-mutant melanoma cell lines from patients not previously treated with target therapy, 21 (42.9%) showed strong primary resistance (IC50 > 1 μM) to a BRAFV600E inhibitor.