A light-resuming strategy as a screening method for selecting Sec61 inhibitors down-modulating PD-L1 expression.

The perturbation of protein translocation into the secretory pathway using Sec61 translocon inhibitors is a novel and promising strategy for tackling many pathological situations, including cancer and viral infections. However, a highly sensitive and direct screening platform for selecting Sec61 inhibitors is unavailable. Here, we develop a "resuming luminescence upon translocation interference" (RELITE) assay capable of selecting Sec61 inhibitors in a single round of screening.

ZNF224 enhances the oncogenic function of p21 via p53 and AKT pathways in melanoma.

Expression of zinc finger protein 224 (ZNF224) is deregulated in various hematological and solid cancers, where its high protein levels correlate well with faster progression and worse prognosis due to activation of oncogenic pathways involved in promoting cell growth and survival, inhibiting apoptosis, and sustaining invasion and metastasis. In previous works, we identified ZNF224 as one of the mediators of the transforming growth factor beta (TGF-β)-induced pro-tumoral activities in melanoma. In the present study, we thoroughly investigated the molecular mechanisms underlying the oncogenic role of ZNF224 in this kind of cancer.

Exploring the potential of selective FKBP51 inhibitors on melanoma: an investigation of their in vitro and in vivo effects.

FKBP51 is a marker of melanocyte malignancy, correlating with vertical growth phase and lesion thickness. It promotes the typical features of epithelial to mesenchymal transition and sustains apoptosis resistance. The present study aimed to assess in vitro and in vivo the efficacy against melanoma of selective small molecules targeting FKBP51, called SAFits.

Blueberry-derived exosome like nanovesicles carry RNA cargo into HIEC-6 cells and down-regulate LPS-induced inflammatory gene expression: A proof-of-concept study.

Exosome-like nanovesicles (ELNs) of food origin have received great attention in the last decade, due to the hypothesis that they contain bioactive molecules. ELNs purified from edible species have been shown to be protective and are able to regulate intestinal homeostasis. Despite ELNs being potential rising stars in modern healthy diets and biomedical applications, further research is needed to address underlying knowledge gaps, especially related to the specific molecular mechanism through which they exert their action.

Sperm-carried IGF2: towards the discovery of a spark contributing to embryo growth and development.

Spermatozoa have been shown to carry key RNAs which, according to animal evidence, seem to play a role in early embryo development. In this context, a potential key growth regulator is insulin-like growth factor 2 (IGF2), a highly conserved paternally expressed imprinted gene involved in cell growth and proliferation which, recent observations indicate, is expressed in human spermatozoa. We herein hypothesized that sperm IGF2 gene expression and transmission at fertilization is required to support early embryo development.

Pigmented paravenous retinochoroidal atrophy and retinitis pigmentosa-like phenotype in the same patient: A case series.

Introduction: Concomitant manifestation of PPRCA in one eye and RP-like retinopathy in the fellow eye is a rare clinical entity, with limited published descriptions to date. The aim of this study is to describe comprehensive clinical evaluations and long-term follow-up of three patients affected by this clinical picture.

Methods: Three patients with concurrent PPRCA and RP-like retinopathy were prospectively re-evaluated and comprehensive assessments were performed.

Metabolic vulnerability of cancer stem cells and their niche.

Cancer stem cells (CSC) are the leading cause of the failure of anti-tumor treatments. These aggressive cancer cells are preserved and sustained by adjacent cells forming a specialized microenvironment, termed niche, among which tumor-associated macrophages (TAMs) are critical players. The cycle of tricarboxylic acids, fatty acid oxidation path, and electron transport chain have been proven to play central roles in the development and maintenance of CSCs and TAMs.

The FKBP51s Splice Isoform Predicts Unfavorable Prognosis in Patients with Glioblastoma.

Unlabelled: The primary treatment for glioblastoma (GBM) is removing the tumor mass as defined by MRI. However, MRI has limited diagnostic and predictive value. Tumor-associated macrophages (TAM) are abundant in GBM tumor microenvironment (TME) and are found in peripheral blood (PB).

Scaffold proteins of cancer signaling networks: The paradigm of FK506 binding protein 51 (FKBP51) supporting tumor intrinsic properties and immune escape.

Scaffold proteins are crucial regulators of signaling networks, and their abnormal expression may favor the development of tumors. Among the scaffold proteins, immunophilin covers a unique role as 'protein-philin' (Greek 'philin' = friend) that interacts with proteins to guide their proper assembly. The growing list of human syndromes associated with the immunophilin defect underscores the biological relevance of these proteins that are largely opportunistically exploited by cancer cells to support and enable the tumor's intrinsic properties.

FKBP51 plays an essential role in Akt ubiquitination that requires Hsp90 and PHLPP.

FKBP51 plays a relevant role in sustaining cancer cells, particularly melanoma. This cochaperone participates in several signaling pathways. FKBP51 forms a complex with Akt and PHLPP, which is reported to dephosphorylate Akt.

Alternative splicing of FKBP5 gene exerts control over T lymphocyte expansion.

FKBP51 is constitutively expressed by immune cells. As other FKBP family members, FKBP51 acts as a coreceptor for the natural products FK506 and rapamycin, which exhibit immunosuppressive effects. However, little is known about the intrinsic role of this large FKBP in the primary function of lymphocytes, that is, the adaptive immune response against foreign antigens, for example, pathogens.

Biological relevance of ZNF224 expression in chronic lymphocytic leukemia and its implication IN NF-kB pathway regulation.

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease, whose presentation and clinical course are highly variable. Identification of novel prognostic factors may contribute to improving the CLL classification and providing indications for treatment options. The zinc finger protein ZNF224 plays a key role in cell transformation, through the control of apoptotic and survival pathways.

Hyper-reflective vitreous spots in central retinal artery occlusion: An unusual finding in two cases.

Purpose: To present two consecutive cases of Central Retinal Artery Occlusion (CRAO) with unusual Optical Coherence Tomography (OCT) presentation of Hyperreflective Spots (HRS) in the posterior vitreous.

Case Report: The first patient was a 59 years-old male who developed CRAO in the post-operative period after aortic valve replacement. OCT scans revealed the presence of many HRS in the posterior vitreous, remarkably decreased in number at two months follow-up.

Genetic evaluation in phenotypically discordant monozygotic twins with Coats Disease.

Purpose: To report the unique case of a pair of phenotypically discordant monozygotic twins, with one of them affected by unilateral Coats disease.

Case Report: Both patients underwent a complete ophthalmologic evaluation and were genetically tested with whole-exome sequencing (WES). Any known or unknown potential genetic determinant of Coats disease wasn't found.

Retinal vascular occlusion and SARS-CoV-2 vaccination.

Purpose: To assess the clinical and retinal imaging features of patients in whom retinal vascular occlusion (VO) had developed in temporal associations with COVID-19 vaccination.

Methods: In this retrospective case series, all consecutive adult patients with new onset VO within 6 weeks of vaccination against COVID-19 were included in the study between May 1 and October 31, 2021. All patients had a systemic medical health assessment, full ophthalmic evaluation, and complete fundus imaging.

Exploring a peptide nucleic acid-based antisense approach for CD5 targeting in chronic lymphocytic leukemia.

We herein report an innovative antisense approach based on Peptide Nucleic Acids (PNAs) to down-modulate CD5 expression levels in chronic lymphocytic leukemia (CLL). Using bioinformatics tools, we selected a 12-mer tract of the CD5 mRNA as the molecular target and synthesized the complementary and control PNA strands bearing a serine phosphate dipeptide tail to enhance their water solubility and bioavailability. The specific recognition of the 12-mer DNA strand, corresponding to the target mRNA sequence by the complementary PNA strand, was confirmed by non-denaturing polyacrylamide gel electrophoresis, thermal difference spectroscopy, circular dichroism (CD), and CD melting studies.

Metabolites Profiling of Melanoma Interstitial Fluids Reveals Uridine Diphosphate as Potent Immune Modulator Capable of Limiting Tumor Growth.

Tumor interstitial fluid (TIF) surrounds and perfuses tumors and collects ions, metabolites, proteins, and extracellular vesicles secreted by tumor and stromal cells. Specific metabolites, accumulated within the TIF, could induce metabolic alterations of immune cells and shape the tumor microenvironment. We deployed a metabolomic approach to analyze the composition of melanoma TIF and compared it to the plasma of C57BL6 mice, engrafted or not with B16-melanoma cells.

FKBP51 Affects TNF-Related Apoptosis Inducing Ligand Response in Melanoma.

Melanoma is one of the most immunogenic tumors and has the highest potential to elicit specific adaptive antitumor immune responses. Immune cells induce apoptosis of cancer cells either by soluble factors or by triggering cell-death pathways. Melanoma cells exploit multiple mechanisms to escape immune system tumoricidal control.

PD-L1 Expression Fluctuates Concurrently with Cyclin D in Glioblastoma Cells.

Despite Glioblastoma (GBM) frequently expressing programmed cell death ligand-1 (PD-L1), treatment with anti-programmed cell death-1 (PD1) has not yielded brilliant results. Intratumor variability of PD-L1 can impact determination accuracy. A previous study on mouse embryonic fibroblasts (MEFs) reported a role for cyclin-D in control of PD-L1 expression.

More blastocysts are produced from fewer oocytes in ICSI compared to IVF - results from a sibling oocytes study and definition of a new key performance indicator.

Background: Which fertilization method, between ICSI and IVF in split insemination treatments, has the highest clinical efficiency in producing clinically usable blastocyst?

Methods: 211 infertile couples underwent split insemination treatments for a non-severe male factor. 1300 metaphase II (MII) oocytes were inseminated by conventional IVF and 1302 MII oocytes were micro-injected with the same partner's semen. Embryo development until blastocyst stage on day V and clinical outcomes were valuated trough conventional key performance indicators (KPI), and new KPIs such as blastocyst rate per used MII oocytes and the number of MII oocytes to produce one clinically usable blastocyst from ICSI and IVF procedures.

Combining Magnetic Resonance Imaging with Systemic Monocyte Evaluation for the Implementation of GBM Management.

Magnetic resonance imaging (MRI) is the gold standard for glioblastoma (GBM) patient evaluation. Additional non-invasive diagnostic modalities are needed. GBM is heavily infiltrated with tumor-associated macrophages (TAMs) that can be found in peripheral blood.

BFAR coordinates TGFβ signaling to modulate Th9-mediated cancer immunotherapy.

TGFβ is essential for the generation of anti-tumor Th9 cells; on the other hand, it causes resistance against anti-tumor immunity. Despite recent progress, the underlying mechanism reconciling the double-edged effect of TGFβ signaling in Th9-mediated cancer immunotherapy remains elusive. Here, we find that TGFβ-induced down-regulation of bifunctional apoptosis regulator (BFAR) represents the key mechanism preventing the sustained activation of TGFβ signaling and thus impairing Th9 inducibility.

Thrombocytopenia Complicating Transcatheter Aortic Valve Implantation: Differences Between Two New-Generation Devices.

Thrombocytopenia after TAVI is common and clinically detrimental. Retrospectively, we observed Portico recipients had a more profound platelet drop than Evolut recipients. We thus investigated periprocedural platelet damage and/orpro-inflammatory state in 64 TAVI recipients at baseline and after implantation.