Empagliflozin prevents angiotensin II-induced hypertension related micro and macrovascular endothelial cell activation and diastolic dysfunction in rats despite persistent hypertension: Role of endothelial SGLT1 and 2.

SGLT2 inhibitors (SGLT2i) showed pronounced beneficial effects in patients with heart failure but the underlying mechanisms remain unclear. We evaluated the effect of empagliflozin, selective SGLT2i, on hypertension-induced cardiac and vascular dysfunction. Male Wistar rats received diet with or without empagliflozin (30 mg/kg/day).

In Search for the Missing Link in APECED-like Conditions: Analysis of the Gene in a Series of 48 Patients.

Autoimmune diseases are a heterogeneous group of disorders of the immune system. They can cluster in the same individual, revealing various preferential associations for polyendocrine autoimmune syndromes. Clinical observation, together with advances in genetics and the understanding of pathophysiological processes, has further highlighted that autoimmunity can be associated with immunodeficiency; autoimmunity may even be the first primary immunodeficiency manifestation.

Multimodal Imaging Approach in a Patient with Vogt-Koyanagi-Harada-like Syndrome Due to Dabrafenib and Trametinib Use for Cutaneous Melanoma.

Purpose: To describe a case of ocular inflammation associated with dabrafenib and trametinib chemotherapy for cutaneous melanoma by using a multimodal image approach.

Materials And Methods: We report on a 51-year-old woman with Vogt-Koyanagi-Harada-like syndrome, which occurred while she was undergoing treatment with dabrafenib and trametinib for cutaneous melanoma. The patient complained of sudden, bilateral vision loss of 2 days' duration.

Preparation and In Vitro Evaluation of RITUXfab-Decorated Lipoplexes to Improve Delivery of siRNA Targeting C1858T PTPN22 Variant in B Lymphocytes.

Autoimmune endocrine disorders, such as type 1 diabetes (T1D) and thyroiditis, at present are treated with only hormone replacement therapy. This emphasizes the need to identify personalized effective immunotherapeutic strategies targeting T and B lymphocytes. Among the genetic variants associated with several autoimmune disorders, the C1858T polymorphism of the protein tyrosine phosphatase non-receptor type 22 () gene, encoding for Lyp variant R620W, affects the innate and adaptive immunity.

p53 Activation Effect in the Balance of T Regulatory and Effector Cell Subsets in Patients With Thyroid Cancer and Autoimmunity.

Carcinomas evade the host immune system by negatively modulating CD4+ and CD8+ T effector lymphocytes through forkhead box protein 3 (FOXP3) positive T regulatory cells' increased activity. Furthermore, interaction of the programmed cell death 1 (PD1) molecule and its ligand programmed cell death ligand 1 (PDL1) inhibits the antitumor activity of PD1+ T lymphocytes. Immunotherapy has become a powerful strategy for tailored cancer patients' treatment both in adult and pediatric patients aiming to generate potent antitumor responses.

Fluorescent nanocarriers targeting VCAM-1 for early detection of senescent endothelial cells.

Endothelial senescence has been identified as an early event in the development of endothelial dysfunction, a hallmark of cardiovascular disease. This study developed theranostic nanocarriers (NC) decorated with VCAM-1 antibodies (NC-VCAM-1) in order to target cell surface VCAM-1, which is overexpressed in senescent endothelial cells (ECs) for diagnostic and therapeutic purposes. Incubation of Ang II-induced premature senescent ECs or replicative senescent ECs with NC-VCAM-1 loaded with lipophilic fluorescent dyes showed higher fluorescence signals than healthy EC, which was dependent on the NC size and VCAM-1 antibodies concentration, and not observed following masking of VCAM-1.

Covid-19 and acute conjunctivitis: Controversial data from a tertiary refferral Italian center.

Purpose: Although acute conjunctivitis has been listed from the beginning as a possible sign of COVID-19, the likelihood of this association remains unclear. The aim of this study was to investigate the relationship between COVID-19 and conjunctivitis.

Methods: In this retrospective, observational study, we recruited all patients with signs and symptoms of acute conjunctivitis seen at the Eye Emergency Department (ED), Turin Eye Hospital, between 01/01/2020 and 12/05/2020 and cross-checked our data with the Piedmont Region online COVID-19 registry in the same period.

The dark side of gamma-glutamyltransferase (GGT): Pathogenic effects of an 'antioxidant' enzyme.

Having long been regarded as just a member in the cellular antioxidant systems, as well as a clinical biomarker of hepatobiliary diseases and alcohol abuse, gamma-glutamyltransferase (GGT) enzyme activity has been highlighted by more recent research as a critical factor in modulation of redox equilibria within the cell and in its surroundings. Moreover, due to the prooxidant reactions which can originate during its metabolic function in selected conditions, experimental and clinical studies are increasingly involving GGT in the pathogenesis of several important disease conditions, such as atherosclerosis, cardiovascular diseases, cancer, lung inflammation, neuroinflammation and bone disorders. The present article is an overview of the laboratory findings that have prompted an evolution in interpretation of the significance of GGT in human pathophysiology.

Thrombin Induces Angiotensin II-Mediated Senescence in Atrial Endothelial Cells: Impact on Pro-Remodeling Patterns.

Background: Besides its well-known functions in hemostasis, thrombin plays a role in various non-hemostatic biological and pathophysiologic processes. We examined the potential of thrombin to promote premature atrial endothelial cells (ECs) senescence.

Methods And Results: Primary ECs were isolated from porcine atrial tissue.

Angiotensin II-induced redox-sensitive SGLT1 and 2 expression promotes high glucose-induced endothelial cell senescence.

High glucose (HG)-induced endothelial senescence and dysfunction contribute to the increased cardiovascular risk in diabetes. Empagliflozin, a selective sodium glucose co-transporter2 (SGLT2) inhibitor, reduced the risk of cardiovascular mortality in type 2 diabetic patients but the protective mechanism remains unclear. This study examines the role of SGLT2 in HG-induced endothelial senescence and dysfunction.

γ-Glutamyltransferase enzyme activity of cancer cells modulates L-γ-glutamyl-p-nitroanilide (GPNA) cytotoxicity.

L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine (Gln) transporter ASCT2, but recent studies have demonstrated that it is also able to inhibit other sodium-dependent and independent amino acid transporters. Moreover, GPNA is a well known substrate of the enzyme γ-glutamyltransferase (GGT). Our aim was to evaluate the effect of GGT-mediated GPNA catabolism on cell viability and Gln transport.

Antitumoral effects of pharmacological ascorbate on gastric cancer cells: GLUT1 expression may not tell the whole story.

The recently reported results of Lu (Theranostics. 2018; 8: 1312-26) - highlighting GLUT1 expression as a marker for sensitivity of gastric cancer cells to therapeutic doses of ascorbate - are discussed in the light of additional factors potentially affecting the underlying processes, such as the concomitant expression of membrane gamma-glutamyltransferase activity, the resistance of cancer cells to oxidative injury and other known biomarkers.

The optokinetic response is effective to assess objective visual acuity in patients with cataract and age-related macular degeneration.

Purpose: To estimate objective visual acuity in subjects suffering from cataract and age-related macular degeneration via the optokinetic response evoked by a non-conventional induction method (oktotype); in addition, to compare such objective outcome with the subjective acuity based on the ETDRS charts.

Methods: Patients were presented with 13 sequences of symbols arranged horizontally to form a serial pattern, moving from left to right at a constant rate. In each sequence, the size of the stimuli was reduced progressively, while the operator checked for the disappearance of the optokinetic response via a small video camera mounted on the test lens frame.

Potential mechanisms underlying cardiovascular protection by polyphenols: Role of the endothelium.

Epidemiological studies have indicated that regular intake of polyphenol-rich diets such as red wine and tea, are associated with a reduced risk of cardiovascular diseases. The beneficial effect of polyphenol-rich products has been attributable, at least in part, to their direct action on the endothelial function. Indeed, polyphenols from tea, grapes, cacao, berries, and plants have been shown to activate endothelial cells to increase the formation of potent vasoprotective factors including nitric oxide (NO) and to delay endothelial ageing.

Regulation of protein function by S-nitrosation and S-glutathionylation: processes and targets in cardiovascular pathophysiology.

Decades of chemical, biochemical and pathophysiological research have established the relevance of post-translational protein modifications induced by processes related to oxidative stress, with critical reflections on cellular signal transduction pathways. A great deal of the so-called 'redox regulation' of cell function is in fact mediated through reactions promoted by reactive oxygen and nitrogen species on more or less specific aminoacid residues in proteins, at various levels within the cell machinery. Modifications involving cysteine residues have received most attention, due to the critical roles they play in determining the structure/function correlates in proteins.

Oxidative stress enhances and modulates protein S-nitrosation in smooth muscle cells exposed to S-nitrosoglutathione.

Among S-nitrosothiols showing reversible binding between NO and -SH group, S-nitrosoglutathione (GSNO) represents potential therapeutics to treat cardiovascular diseases (CVD) associated with reduced nitric oxide (NO) availability. It also induces S-nitrosation of proteins, responsible for the main endogenous storage form of NO. Although oxidative stress parallels CVD development, little is known on the ability of GSNO to restore NO supply and storage in vascular tissues under oxidative stress conditions.

Effect of the three-dimensional organization of liver cells on the biogenesis of the γ-glutamyltransferase fraction pattern.

Context Four gamma-glutamyltransferase (GGT) fractions with different molecular weights (big-, medium-, small- and free-GGT) are detectable in human plasma. Objective Verify if liver cells can release all four GGT fractions and if the spatial cell organization influences their release. Methods Hepatoma (HepG2) and melanoma (Me665/2/60) cells were cultured as monolayers or spheroids.

Monocytes/macrophages activation contributes to b-gamma-glutamyltransferase accumulation inside atherosclerotic plaques.

Background: Gamma-glutamyltransferase (GGT) is a well-established independent risk factor for cardiovascular mortality related to atherosclerotic disease. Four GGT fractions have been identified in plasma, but only b-GGT fraction accumulates in atherosclerotic plaques, and correlates with other histological markers of vulnerability. The present study was aimed to evaluate whether macrophagic lineage cells may provide a source of b-GGT within the atherosclerotic plaque.

Endothelin system mRNA variation in the heart of Zucker rats: evaluation of a possible balance with natriuretic peptides.

Background And Aims: The deregulation of neurohormonal systems, including the natriuretic peptide (NP) and endothelin (ET) systems, may increase the possibility of developing obesity-related risk. The aim of our paper was to evaluate ET system mRNA variation in heart of the Zucker rat model together with the simultaneous evaluation of the NP system transcriptomic profile. In order to analyze the link between the ET-1 system and the inflammatory process, the cardiac expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α was also measured.

Impact of obesity on the expression profile of natriuretic peptide system in a rat experimental model.

Natriuretic peptides (NPs) play an important role in obesity and aim of this study was to evaluate, in cardiac tissue of obese Zucker rats (O, n = 29) their transcriptomic profile compared to controls (CO, n = 24) by Real-Time PCR study; CNP protein expression was evaluated by immunostaining and immunometric tests. Myocardial histology was performed, confirming no alteration of organ structure. While ANP and BNP are cardiac peptides, CNP is mainly an endothelial hormone; thus its expression, as well as that of NPR-B and NPR-C, was also evaluated in kidney and lung of an animal subgroup (n = 20).

[Obstructive jaundice caused by residual and/or recurrent choledochal lithiasis: endoscopic and surgical treatment].

Results of surgical and endoscopic treatment in 79 patients (58 females and 21 males, age 40-89, mean 62), affected with jaundice, due to secondary choledochal lithiasis, are reported. Thirty-four patients (43%) underwent surgical operation: choledochotomy and T-tube 12, choledocho-jejunostomy 4, choledochoduodenostomy 3, papillosphincteroplasty 15. In 45 patients (57%) EST has been performed.

[Treatment of breast carcinoma. Our experience].

The results of a study on 848 patients with breast carcinoma having maximum diameter less than or equal to 2 cm, that underwent a surgical treatment at the Institute of Special Surgical Pathology B (1980-82) and at the Institute of Surgical Clinic I (1980-89) are presented. The study has the purpose of evaluating, by the analysis of ten years surviving curves, the effectiveness of different types of interventions: Halsted radical mastectomy (98 patients), Patey radical mastectomy (245 patients) and Madden radical mastectomy (151 patients), quadrantectomy (260 patients). The age of patients ranges from 29 years to 92 years (average 56 years).