Effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as switch strategy in virologically-suppressed patients: real world data from a monocentric cohort.

Introduction: BIC/FTC/TAF showed efficacy and tolerability in randomized trials as a switch strategy in virologically-suppressed people living with HIV. We evaluated its effectiveness in a real-life setting.

Methods: A retrospective monocentric cohort including 431 virologically-suppressed (HIV-RNA <50 copies/ml) people switching to BIC/FTC/TAF in the period 2018-2022 was evaluated.

HIV and vicarious stigma in a cohort of people living with HIV in Italy: What happens when the stigma is fueled by healthcare providers?

Vicarious stigma shows how indirect stigmatizing experiences can lead people living with HIV (PLWH) to feel discriminated against. We enrolled 350 PLWH, who were administered a 17-item questionnaire to investigate a subjective experience of stigma experienced in the hospital care setting. We found that at least once 215 PLWH (61.

Two-Drug Regimen Containing Darunavir: Metabolic Evaluation of an Old Dual Therapy.

Regimens containing darunavir are one of the first one with two drugs that demonstrated good efficacy as a simplification strategy. We wanted to describe the characteristics of patients followed in our center on a dual therapy regimen containing darunavir evaluating the metabolic aspects during follow-ups. We collected data from 208 patients switching to lamivudine plus darunavir with either ritonavir or cobicistat between 2010 and 2019.

Cardiovascular Disease Risk in a Cohort of Virologically Suppressed People Living with HIV Switching to Doravirine: Preliminary Data from the Real Life.

Aim of this study is to assess the impact of doravirine (DOR)-based regimens on cardiovascular risk in treatment-experienced people living with HIV (PLWHIV). We retrospectively analyzed a cohort of 40 treatment-experienced PLWHIV switching to a DOR-based three-drug regimen, evaluating 10-year risk of manifesting clinical cardiovascular diseases (CD) through the Framingham Risk Score at baseline, 12, and 24 weeks of follow-up. At baseline, median predicted 10-year risk of cardiovascular disease (10Y-CD) was 8.

Are we ready for long-acting? A feasibility evaluation of long-acting cabotegravir-rilpivirine in clinical practice.

Cabotegravir and rilpivirine are the first drugs to be approved as injectable therapy to treat individuals with HIV. Despite encouraging results, the guidelines specify strict criteria for eligibility that could limit the feasibility of this strategy. We collected the clinical data of HIV-positive patients who were being treated at a single, third-level center in Italy.

Evaluation of doravirine-based regimen population target in a large Italian clinical center.

Background: Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for HIV-1 infection treatment. Because of its genetic barrier, DOR appears to be a good alternative in switch strategies compared to other NNRTI. Our aim was to evaluate the percentage of people living with HIV (PLWHIV) followed in our center who could be eligible to a DOR-based regimen.

Viral Encephalitis in Adults: A Narrative Review.

Viral infections of the central nervous system cause frequent hospitalization. The pathogenesis of viral encephalitis involves both the direct action of invading pathogens and the damage generated by the inflammatory reaction they trigger. The type of signs and symptoms presented by the patient depends on the severity and location of the ongoing inflammatory process.

Short Communication: Comparing Lamivudine+Dolutegravir and Bictegravir/Emtricitabine/Tenofovir Alafenamide as Switch Strategies: Preliminary Results from Clinical Practice.

We tried to investigate and compare the safety of a dual therapy (DT) with dolutegravir+lamivudine (DTG +3TC) versus bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). We performed a retrospective analysis in a cohort of virologically suppressed HIV+ pts switching to DT or BIC in our center. Primary endpoint was to evaluate time to treatment discontinuation (TD) for any cause.

FKBP51s signature in peripheral blood mononuclear cells of melanoma patients as a possible predictive factor for immunotherapy.

The inhibitory immune checkpoint PD-L1/PD1 promotes the alternative splicing of the FKBP5 gene, resulting in increased expression of its variant 4 in the peripheral blood mononuclear cells of melanoma patients. The variant 4 transcript is translated into the truncated FKBP51s protein. Given the importance of co-inhibitory signalling in tumour immune escape, here we tested the potential for using FKBP51s expression to predict immunotherapy outcomes.

Tirofiban counteracts endothelial cell apoptosis through the VEGF/VEGFR2/pAkt axis.

Tirofiban is used in the treatment of patients with acute coronary syndrome submitted to percutaneous coronary intervention (PCI). We have, previously, shown that tirofiban stimulates VEGF expression and promotes proliferation of endothelial cells. VEGF is a well known inhibitor of endothelial cell apoptosis.

Effects Of Glycoprotein IIb/IIIa Antagonists: Anti Platelet Aggregation And Beyond.

Background: The use of inhibitors of glycoprotein IIb/IIIa (GPIIb/IIIa) has provided dramatic results in terms of the prevention of acute stent thrombosis and a reduction in major adverse coronary events in patients subjected to percutaneous coronary intervention. GPIIb/IIIa or αIIbβ3 is a member of the β3 subfamily of integrins, which also includes αVβ3. GPIIb/IIIa functions as a receptor for fibrinogen and several adhesion proteins sharing an arginine-glycine-aspartic acid (RGD) sequence.

Carotid artery diameter and wall stiffness in proteinuric renal disease without severely reduced kidney function.

Purpose: To evaluate the carotid artery diameter, and wall thickness and stiffness in patients with glomerulopathy and proteinuria without severely reduced kidney function.

Methods: We compared 30 control subjects to 30 patients with glomerular disease, proteinuria, and glomerular filtration rate > 30 ml/min/1.73 m(2) : membranous glomerulonephritis (n = 13), minimal change disease (n = 2), focal and segmental glomerulosclerosis (n = 3), IgA nephropathy (n = 5), lupus nephritis (n = 5), antiphospholipid antibody nephropathy (n = 1), cryoglobulinemic glomerulonephritis (n = 1).

FKBP51 employs both scaffold and isomerase functions to promote NF-κB activation in melanoma.

Melanoma is the most aggressive skin cancer; its prognosis, particularly in advanced stages, is disappointing largely due to the resistance to conventional anticancer treatments and high metastatic potential. NF-κB constitutive activation is a major factor for the apoptosis resistance of melanoma. Several studies suggest a role for the immunophilin FKBP51 in NF-κB activation, but the underlying mechanism is still unknown.

Molecular Aspects of FKBP51 that Enable Melanoma Dissemination.

FKBP51 (FKBP5 Official Symbol) is large molecular weight member of the FK506 binding protein family, a subfamily of the immunophilin proteins. FKBP51 exerts multiple biological functions in the cell, including modulation of steroid hormone response, immune regulation, cell proliferation, regulation of pAkt levels and control of NF-κB activation. Several lines of evidence support a role for this protein in cancer biology, especially in resistance to chemo- and radio-therapy.

Immunomodulatory pathways regulate expression of a spliced FKBP51 isoform in lymphocytes of melanoma patients.

FKBP51 (gene FKBP5) is an immunophilin capable of immunosuppression expressed in melanoma and lymphocytes. We found increased levels of a spliced FKBP5 variant in the PBMCs of 124 patients with melanoma. This variant encodes for an unknown isoform (FKBP51s).

Pleiotropic roles in cancer biology for multifaceted proteins FKBPs.

Background: FK506 binding proteins (FKBP) are multifunctional proteins highly conserved across the species and abundantly expressed in the cell. In addition to a well-established role in immunosuppression, FKBPs modulate several signal transduction pathways in the cell, due to their isomerase activity and the capability to interact with other proteins, inducing changes in conformation and function of protein partners. Increasing literature data support the concept that FKBPs control cancer related pathways.

Tirofiban induces VEGF production and stimulates migration and proliferation of endothelial cells.

Tirofiban is a fibrinogen receptor antagonist, generated using the tripeptide Arg-Gly-Asp (RGD) as a template. RGD activates integrin receptors and integrin-mediated signals are necessary for normal cells to promote survival and stimulate cell cycle progression. We investigated whether tirofiban activated growth-stimulatory signals in endothelium.

FKBP51 increases the tumour-promoter potential of TGF-beta.

Background: FKBP51 (FKBP5 Official Symbol) is a large molecular weight component of the family of FK506 binding proteins (FKBP). In recent years, research studies from our laboratory highlighted functions for FKBP51 in the control of apoptosis and melanoma progression. FKBP51 expression correlated with the invasiveness and aggressiveness of melanoma.

Cellular and molecular background underlying the diversity in therapeutic responses between primary tumours and metastases.

Metastasis, also called secondary neoplastic disease, is a tumour newly formed in a site different from that of origin, as a consequence of cancer progression and dissemination largely through blood and lymphatic vessels. The ability to form metastases is the main property that distinguishes malignant from benign tumours. Treatments for metastatic cancer are similar in practice to those for primary tumours, but such treatments are mostly palliative; indeed, almost all deaths caused by solid tumours occur in the metastatic phase.

Synergy between enzastaurin doxorubicin in inducing melanoma apoptosis.

Melanoma is resistant to most standard chemotherapeutics. We analysed the combined effect of doxorubicin and enzastaurin on cell death of four melanoma cell lines, namely G361, SK-MEL3, A375 and SAN. Enzastaurin IC50 was calculated by measure of growth inhibition with MTS assay and corresponded to 2 μM; the half maximal cytotoxicity of doxorubicin was obtained at 3 μM dose.

Toxoplasma gondii Dense Granule Antigen 1 stimulates apoptosis of monocytes through autocrine TGF-β signaling.

Monocyte/macrophages represent the first line of defense against protozoan parasites. Different mechanisms of monocyte suppression by Toxoplasma gondii that sustain parasite invasion and persistence have been described, including apoptosis. In the present study, we investigated the effect of microbial excretory–secretory polypeptides, namely the microneme protein MIC3 and the dense granule antigen GRA1, on apoptosis of monocytes from patients with congenital toxoplasmosis and healthy individuals.

Role of FK506-binding protein 51 in the control of apoptosis of irradiated melanoma cells.

FK506-binding protein 51 (FKBP51) is an immunophilin with isomerase activity, which performs important biological functions in the cell. It has recently been involved in the apoptosis resistance of malignant melanoma. The aim of this study was to investigate the possible role of FKBP51 in the control of response to ionizing radiation (Rx) in malignant melanoma.

The effect of FK506 on transforming growth factor beta signaling and apoptosis in chronic lymphocytic leukemia B cells.

Background: Loss of response to transforming growth factor-beta (TGF-beta ) is thought to contribute to the progression of chronic lymphocytic leukemia. Recent findings of over-activation of the TGF-beta signal in FKBP12-knockout mouse prompted us to investigate whether FK506, the canonical ligand of FKBP, can activate the TGF-beta signal in chronic lymphocytic leukemia.

Design And Methods: We studied 62 chronic lymphocytic leukemia samples from patients with Rai/Binet stage 0 to 4 disease.