TERRA G-quadruplex stabilization behind the anti-multiple myeloma activity: Novel insights about resveratrol pleiotropic effects.

Resveratrol (RSV) is a nutraceutical compound belonging to the nonflavonoid polyphenol family, whose antioxidants, anti-inflammatory, and antitumoral properties have been widely investigated. The ability of RSV to provide beneficial effects for neurological, cardiovascular, and cancer disorders rekindled the interest to explore the molecular mechanisms behind its pleiotropic effects, which are due to the modulation of coding and noncoding genes involved in many key biological pathways. With a computational approach, including docking studies and thermodynamics calculations followed by 200-ns-long molecular dynamics and a clustering analysis, we hypothesized the stabilizing binding between RSV and G4 structures of telomeric repeat-containing RNA (TERRA), which is a tumor-suppressive long noncoding RNAs (lncRNA) involved in the regulation of telomere maintenance.

Scaling approaches for the prediction of human clearance of LNA-i-mir-221: A retrospective validation.

LNA-i-miR-221 is a novel microRNA(miRNA)-221 inhibitor designed for the treatment of human malignancies. It has recently undergone phase 1 clinical trial (P1CT) and early pharmacokinetics (PKs) data in cancer patients are now available. We previously used multiple allometric interspecies scaling methods to draw inferences about LNA-i-miR-221 PKs in humans and estimated the patient dose based on the safe and pharmacodynamic (PD) active dose observed in mice, therefore providing a framework for the definition of safe starting and escalation doses for the P1CT.

Diagnostic reproducibility of the 2018 Classification of Gingival Recessions: Comparing photographic and in-person diagnoses.

Background: To assess how the diagnostic reproducibility of the 2018 Classification of Gingival Recession Defects (GRD) could be applied when comparing in-person chairside measurements with photographic measurements.

Methods: Thirty-four GRD were photographed and evaluated by 4 masked operators. For each case, the operators measured twice recession type (RT), recession depth (RD), keratinized tissue width (KTW), gingival thickness (GT), detectability of the cemento-enamel junction (CEJ), and presence of root steps (RSs), chairside, and on photographs.

A systematic review of non-coding RNA therapeutics in early clinical trials: a new perspective against cancer.

Targeting non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), has recently emerged as a promising strategy for treating malignancies and other diseases. In recent years, the development of ncRNA-based therapeutics for targeting protein-coding and non-coding genes has also gained momentum. This review systematically examines ongoing and completed clinical trials to provide a comprehensive overview of the emerging landscape of ncRNA-based therapeutics.

Non-surgical retreatment versus papillary preservation flap surgery for residual pockets: A randomized controlled trial with clinical and patient-reported outcomes.

Aim: To compare the efficacy of non-surgical re-instrumentation (NSR) and papillary preservation flap (PPF) surgery at single-rooted teeth with residual pockets.

Materials And Methods: Patients with at least a residual pocket depth (PD ≥ 5 mm) after Steps I and II were enrolled and randomly assigned to receive NSR or PPF surgery. The primary outcome was PD reduction, and secondary outcomes were clinical attachment level (CAL) change and patient-reported outcome measures (PROMs).

LNA-i-miR-221 activity in colorectal cancer: A reverse translational investigation.

Colorectal cancer (CRC) is one of the most common malignancies and a relevant cause of cancer-related deaths worldwide. Dysregulation of microRNA (miRNA) expression has been associated with the development and progression of various cancers, including CRC. Among them, miR-221 emerged as an oncogenic driver, whose high expression is associated with poor patient prognosis.

Influence of mobility on the long-term risk of tooth extraction/loss in periodontitis patients. A systematic review and meta-analysis.

The aim of this systematic review (SR) was to assess whether tooth mobility (TM) increases the risk of tooth extraction/loss. The protocol was registered in PROSPERO database (CRD42023485425). The focused PECO questions were as follows: (1) "In patients with periodontitis, undergoing periodontal treatment, are teeth affected by mobility at higher risk of being extracted/lost compared to non-mobile teeth, with a minimum follow-up of 10 years?" and (2) "In these patients, does varying degrees of tooth mobility increase the risk of tooth extraction/loss, with a minimum follow-up of 10 years?".

Identification of ADME genes polymorphic variants linked to trastuzumab-induced cardiotoxicity in breast cancer patients: Case series of mono-institutional experience.

Background: Long-term survival induced by anticancer treatments discloses emerging frailty among breast cancer (BC) survivors. Trastuzumab-induced cardiotoxicity (TIC) is reported in at least 5% of HER2+BC patients. However, TIC mechanism remains unclear and predictive genetic biomarkers are still lacking.

Polynucleotides and Hyaluronic Acid (PN-HA) Mixture With or Without Deproteinized Bovine Bone Mineral as a Novel Approach for the Treatment of Deep Infra-Bony Defects: A Retrospective Case-Series.

Polynucleotides and Hyaluronic Acid (PN-HA) mixture showed several effects in modulation of healing process. The aim of this study was to assess the safety and clinical performance of PN-HA alone or in association with Deproteinized Bovine Bone Mineral (DBBM) with papillary preservation flaps (PPF) in the treatment of residual pockets. A total of 43 patients with 55 infra-bony defects were recruited; 30% were smokers.

The impact of COVID-19 on Italian dentists: A cross-sectional survey on 2443 participants.

Objective: To evaluate the impact of COVID-19 pandemic among a sample of Italian dentists in terms of infection, strategies for infection control, organization of the dental clinic, attitude, and behavior.

Material And Methods: This was a cross-sectional survey. The sample consisted of 8000 Italian dentists selected among 63,375 using a computerized random sampling method.

UMG1/CD3ε-bispecific T-cell engager redirects T-cell cytotoxicity against diffuse large B-cell lymphoma.

UMG1 is a unique epitope of CD43, not expressed by normal cells and tissues of haematopoietic and non-haematopoietic origin, except thymocytes and a minority (<5%) of peripheral blood T lymphocytes. By immunohistochemistry analysis of tissue microarray and pathology slides, we found high UMG1 expression in 20%-24% of diffuse large B-cell lymphomas (DLBCLs), including highly aggressive BCL2 and CD20 cases. UMG1 membrane expression was also found in DLBCL bone marrow-infiltrating cells and established cell lines.

Eosinophil Cationic Protein Variation in Patients with Asthma and CRSwNP Treated with Dupilumab.

Background: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a "type 2" (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5.

An Uncharacterised lncRNA Coded by the ASAP1 Locus Is Downregulated in Serum of Type 2 Diabetes Mellitus Patients.

Diabetes mellitus (DM) is a complex and multifactorial disease characterised by high blood glucose. Type 2 Diabetes (T2D), the most frequent clinical condition accounting for about 90% of all DM cases worldwide, is a chronic disease with slow development usually affecting middle-aged or elderly individuals. T2D represents a significant problem of public health today because its incidence is constantly growing among both children and adults.

The self-reflexivity in transnational literature: Re-writing the migration in female migrant writers.

The main aim of this paper is to discuss the socio-political meaning of the transnational literary production made by female migrant writers. Thus, it analyses their role in the framework of the 'hybrid' literary production of the 21st century in Europe, such as Spain and Italy. Moving away from the idea of national literatures, this paper investigates literature as a geographical and emotional inquiry point and friction between languages, ideas, practices, literary institutions, female authors, and female voices in today's markets.

Safety and activity of the first-in-class locked nucleic acid (LNA) miR-221 selective inhibitor in refractory advanced cancer patients: a first-in-human, phase 1, open-label, dose-escalation study.

Background: We developed a 13-mer locked nucleic acid (LNA) inhibitor of miR-221 (LNA-i-miR-221) with a full phosphorothioate (PS)-modified backbone. This agent downregulated miR-221, demonstrated anti-tumor activity against human xenografts in mice, and favorable toxicokinetics in rats and monkeys. Allometric interspecies scaling allowed us to define the first-in-class LNA-i-miR-221 safe starting dose for the clinical translation.

Hit identification of novel small molecules interfering with MALAT1 triplex by a structure-based virtual screening.

Nowadays, RNA is an attractive target for the design of new small molecules with different pharmacological activities. Among several RNA molecules, long noncoding RNAs (lncRNAs) are extensively reported to be involved in cancer pathogenesis. In particular, the overexpression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays an important role in the development of multiple myeloma (MM).

Barcoded Consortium Infections: A Scalable, Internally Controlled Method to Study Host Cell Binding and Invasion by Pathogenic Bacteria.

Bacterial host cell invasion has routinely been investigated by gentamicin protection assays, which are laborsome and suffer from pronounced experimental noise. This chapter describes an internally controlled, medium- to high-throughput method that resolves the capacity of multiple Salmonella virulence factor mutant strains to bind and invade host cells. The method, widely applicable to also other pathogens, is based on the combination of consortia of genetically tagged isogenic bacterial strains and a modified gentamicin protection assay.

Chemoselective bicyclobutane-based mass spectrometric detection of biological thiols uncovers human and bacterial metabolites.

Sulfur is an essential element of life. Thiol-containing metabolites in all organisms are involved in the regulation of diverse biological processes. Especially, the microbiome produces bioactive metabolites or biological intermediates of this compound class.

A Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) for ovarian cancer.

Background: Pronectins™ are a new class of fibronectin-3-domain 14th-derived (14Fn3) antibody mimics that can be engineered as bispecific T cell engager (BTCE) to redirect immune effector cells against cancer. We describe here the in vitro and in vivo activity of a Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) against Epithelial Ovarian Cancer (EOC).

Methods: pAXLxCD3ε T-cell mediated cytotoxicity was evaluated by flow cytometry and bioluminescence.

Multiple coronally advanced flap with a selective use of connective tissue graft: A 3-year prospective clinical and histological study.

Background: The purpose of the present study was to prospectively evaluate the 3-year changes in the gingival dimensions following multiple coronally advanced flap (MCAF) with selective use of connective tissue graft (CTG). In addition, the secondary aim was to histologically identify the factors related to phenotype changes.

Methods: Twenty patients treated with MCAF and site-specific application of a CTG were available for the 3-year follow-up.

The First-In-Class Anti-AXL×CD3ε Pronectin™-Based Bispecific T-Cell Engager Is Active in Preclinical Models of Human Soft Tissue and Bone Sarcomas.

Sarcomas are heterogeneous malignancies with limited therapeutic options and a poor prognosis. We developed an innovative immunotherapeutic agent, a first-in-class Pronectin™-based Bispecific T-Cell Engager (pAXL×CD3ε), for the targeting of AXL, a TAM family tyrosine kinase receptor highly expressed in sarcomas. AXL expression was first analyzed by flow cytometry, qRT-PCR, and Western blot on a panel of sarcoma cell lines.

TERRA G-quadruplex stabilization as a new therapeutic strategy for multiple myeloma.

Background: Multiple myeloma (MM) is a hematologic malignancy characterized by high genomic instability, and telomere dysfunction is an important cause of acquired genomic alterations. Telomeric repeat-containing RNA (TERRA) transcripts are long non-coding RNAs involved in telomere stability through the interaction with shelterin complex. Dysregulation of TERRAs has been reported across several cancer types.

Exploiting DNA Ligase III addiction of multiple myeloma by flavonoid Rhamnetin.

Background: DNA ligases are crucial for DNA repair and cell replication since they catalyze the final steps in which DNA breaks are joined. DNA Ligase III (LIG3) exerts a pivotal role in Alternative-Non-Homologous End Joining Repair (Alt-NHEJ), an error-prone DNA repair pathway often up-regulated in genomically unstable cancer, such as Multiple Myeloma (MM). Based on the three-dimensional (3D) LIG3 structure, we performed a computational screening to identify LIG3-targeting natural compounds as potential candidates to counteract Alt-NHEJ activity in MM.