ERK5 suppression overcomes FAK inhibitor resistance in mutant KRAS-driven non-small cell lung cancer.

Mutated KRAS serves as the oncogenic driver in 30% of non-small cell lung cancers (NSCLCs) and is associated with metastatic and therapy-resistant tumors. Focal Adhesion Kinase (FAK) acts as a mediator in sustaining KRAS-driven lung tumors, and although FAK inhibitors are currently undergoing clinical development, clinical data indicated that their efficacy in producing long-term anti-tumor responses is limited. Here we revealed two FAK interactors, extracellular-signal-regulated kinase 5 (ERK5) and cyclin-dependent kinase 5 (CDK5), as key players underlying FAK-mediated maintenance of KRAS mutant NSCLC.

A Cellular Model of Amyotrophic Lateral Sclerosis to Study the Therapeutic Effects of Extracellular Vesicles from Adipose Mesenchymal Stem Cells on Microglial Activation.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons (MNs) in the brain and spinal cord, leading to progressive paralysis and death. Increasing evidence indicates that neuroinflammation plays an important role in ALS's pathogenesis and disease progression. Neuroinflammatory responses, primarily driven by activated microglia and astrocytes, and followed by infiltrating peripheral immune cells, contribute to exacerbate/accelerate MN death.

Late orbital radiotherapy combined with intravenous methylprednisolone in the management of long-lasting active graves' orbitopathy: a case report and literature review.

Purpose: To present a case and review the literature on Orbital Radiotherapy (OR) combined with intravenous methylprednisolone, focusing on its late application in patients with long-lasting active Graves' Orbitopathy (GO). Additionally, we suggest emerging perspective for future research in this context.

Method: Relevant literature (randomized controlled studies, retrospective studies and reviews) was explored on PubMed from January 1973 to January 2024, searching "orbital radiotherapy" & "Graves disease".

SIRT6 promotes metastasis and relapse in HER2-positive breast cancer.

The histone deacetylase sirtuin 6 (SIRT6) has been endowed with anti-cancer capabilities in many tumor types. Here, we investigate the impact of SIRT6-overexpression (SIRT6-OE) in Delta16HER2 mice, which are a bona fide model of HER2-positive breast cancer. After an initial delay in the tumor onset, SIRT6-OE induces a more aggressive phenotype of Delta16HER2 tumors promoting the formation of higher number of tumor foci and metastases than controls.

Temporomandibular joint involvement in psoriatic arthritis: a prospective clinical and ultrasonographic study.

Objectives: To evaluate the prevalence of temporomandibular disorders (TMD) in a monocentric cohort of patients affected by psoriatic arthritis (PsA), and to investigate the accuracy of temporomandibular joint (TMJ) ultrasound (US) compared with clinical evaluation and clinimetric composite index in assessing TMJ involvement.

Methods: We conducted a prospective cohort study of patients diagnosed with PsA who underwent at least one TMJ US examination and maxillofacial surgeon's evaluation between 2018 and 2021. The rheumatology physician's interpretation of each TMJ US exam (presence/absence of TMD) was compared with psoriatic arthritis disease activity indexes and maxillofacial surgeon's clinical judgement (presence/absence of TMD signs and/or symptoms).

Single-cell proteo-genomic reveals a comprehensive map of centrosome-associated spliceosome components.

Ribonucleoprotein (RNP) condensates are crucial for controlling RNA metabolism and splicing events in animal cells. We used spatial proteomics and transcriptomic to elucidate RNP interaction networks at the centrosome, the main microtubule-organizing center in animal cells. We found a number of cell-type specific centrosome-associated spliceosome interactions localized in subcellular structures involved in nuclear division and ciliogenesis.

Repurposing pentamidine using hyaluronic acid-based nanocarriers for skeletal muscle treatment in myotonic dystrophy.

In a context of drug repurposing, pentamidine (PTM), an FDA-approved antiparasitic drug, has been proposed to reverse the splicing defects associated in myotonic dystrophy type 1 (DM1). However, clinical use of PTM is hinder by substantial toxicity, leading to find alternative delivery strategies. In this work we proposed hyaluronic acid-based nanoparticles as a novel encapsulation strategy to efficiently deliver PTM to skeletal muscles cells.

Ozone at low concentration modulates microglial activity in vitro: A multimodal microscopy and biomolecular study.

Oxygen-ozone (O -O ) therapy is an adjuvant/complementary treatment based on the activation of antioxidant and cytoprotective pathways driven by the nuclear factor erythroid 2-related factor 2 (Nrf2). Many drugs, including dimethyl fumarate (DMF), that are used to reduce inflammation in oxidative-stress-related neurodegenerative diseases, act through the Nrf2-pathway. The scope of the present investigation was to get a deeper insight into the mechanisms responsible for the beneficial result of O -O treatment in some neurodegenerative diseases.

The Role of Ultrasound in Temporomandibular Joint Disorders: An Update and Future Perspectives.

Temporomandibular joint (TMJ) disorder is the second most common chronic pain condition affecting the general population after back pain. It encompasses a complex set of conditions, manifesting with jaw pain and limitation in mouth opening, influencing chewing, eating, speaking, and facial expression. TMJ dysfunction could be related to mechanical abnormalities or underlying inflammatory arthropathies, such as rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA).

The transcriptional profile of adipose-derived stromal cells (ASC) mirrors the whitening of adipose tissue with age.

Multipotent stem cells persist within the stromal vascular fraction (SVF) of adipose tissue during adulthood. These cells, commonly referred to as adipose-derived stromal cells (ASC), have been extensively investigated over the past years as a promising therapeutic tool based on their regenerative and immunomodulatory properties. However, how ASC might mirror the age-related alteration of the fat they reside in remains unclear.

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro.

Oxygen-ozone (O-O) therapy is increasingly applied as a complementary/adjuvant treatment for several diseases; however, the biological mechanisms accounting for the efficacy of low O concentrations need further investigations to understand the possibly multiple effects on the different cell types. In this work, we focused our attention on fibroblasts as ubiquitous connective cells playing roles in the body architecture, in the homeostasis of tissue-resident cells, and in many physiological and pathological processes. Using an established human fibroblast cell line as an in vitro model, we adopted a multimodal approach to explore a panel of cell structural and functional features, combining light and electron microscopy, Western blot analysis, real-time quantitative polymerase chain reaction, and multiplex assays for cytokines.

Interferon regulatory factor 7 impairs cellular metabolism in aging adipose-derived stromal cells.

Dysregulated immunity and widespread metabolic dysfunctions are the most relevant hallmarks of the passing of time over the course of adult life, and their combination at midlife is strongly related to increased vulnerability to diseases; however, the causal connection between them remains largely unclear. By combining multi-omics and functional analyses of adipose-derived stromal cells established from young (1 month) and midlife (12 months) mice, we show that an increase in expression of interferon regulatory factor 7 (IRF7) during adult life drives major metabolic changes, which include impaired mitochondrial function, altered amino acid biogenesis and reduced expression of genes involved in branched-chain amino acid (BCAA) degradation. Our results draw a new paradigm of aging as the 'sterile' activation of a cell-autonomous pathway of self-defense and identify a crucial mediator of this pathway, IRF7, as driver of metabolic dysfunction with age.

Unilateral Sinus Disease: Not Just Odontogenic! - A Retrospective Study.

Introduction: Unilateral sinus disease (USD), and especially unilateral maxillary sinusitis (UMS), is an increasingly common finding in the ear, nose, and throat and maxillofacial practice. The aim of this retrospective study was to describe the clinical features of a series of patients affected by USD and, in particular, UMS due to sinonasal anatomic anomalies and of odontogenic origin.

Materials And Methods: A total of 292 patients affected by UMS were reviewed.

ACSL3-PAI-1 signaling axis mediates tumor-stroma cross-talk promoting pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by marked fibrosis and low immunogenicity, features that are linked to treatment resistance and poor clinical outcomes. Therefore, understanding how PDAC regulates the desmoplastic and immune stromal components is of great clinical importance. We found that acyl-CoA synthetase long-chain 3 (ACSL3) is up-regulated in PDAC and correlates with increased fibrosis.

Ozone Activates the Nrf2 Pathway and Improves Preservation of Explanted Adipose Tissue In Vitro.

In clinical practice, administration of low ozone (O) dosages is a complementary therapy for many diseases, due to the capability of O to elicit an antioxidant response through the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)-dependent pathway. Nrf2 is also involved in the adipogenic differentiation of mesenchymal stem cells, and low O concentrations have been shown to stimulate lipid accumulation in human adipose-derived adult stem cells in vitro. Thus, O treatment is a promising procedure to improve the survival of explanted adipose tissue, whose reabsorption after fat grafting is a major problem in regenerative medicine.

Impact of COVID-19 epidemic on maxillofacial surgery in Italy.

Maxillofacial departments in 23 surgical units in Italy have been increasingly involved in facing the COVID-19 emergency. Elective surgeries have been progressively postponed to free up beds and offer human and material resources to those infected. We compiled an inventory of 32 questions to evaluate the impact of the SARS-COV2 epidemic on maxillofacial surgery in 23 selected Italian maxillofacial departments.

The ACSL3-LPIAT1 signaling drives prostaglandin synthesis in non-small cell lung cancer.

Enhanced prostaglandin production promotes the development and progression of cancer. Prostaglandins are generated from arachidonic acid (AA) by the action of cyclooxygenase (COX) isoenzymes. However, how cancer cells are able to maintain an elevated supply of AA for prostaglandin production remains unclear.

Mandibular Condyle Osteoma.

Background: Osteoma is a benign tumor composed of both cortical and cancellous bones that increase in size with continuous formation of bone. The pathogenesis is unknown. Osteomas can cause symptoms depending on their location and size.

Transnasal Endoscopic Approach for the Treatment of Medial Orbital Wall Fractures.

The aim of this study is to report a case series of blowout fractures of the medial orbital wall that were treated endoscopically. Isolated fractures of the medial orbital wall are uncommon and can be asymptomatic. Various surgical methods for repairing medial orbital wall fractures have been described.

Orbital Fractures in Childhood.

Pediatric orbital floor fractures exhibit distinctive features that distinguish them from orbital injuries seen in the adult population. This is mainly due to different anatomy and mechanical properties of the orbital bones in children. The management of pediatric orbital floor fractures requires consideration of these factors, including the age of the patient and therefore child's growth potential, using, if possible, a minimally invasive surgical approach.

RAS as Supporting Actor in Breast Cancer.

Oncogenic activation of RAS isoforms leads tumor initiation and progression in many types of cancers and is gaining increasing interest as target for novel therapeutic strategies. In sharp contrast with other types of cancer, the importance of RAS in breast tumorigenesis has long been undermined by the low frequency of its oncogenic mutation in human breast lesions. Nevertheless, a wealth of studies over the last years have revealed how the engagement of RAS function might be mandatory downstream varied oncogenic alterations for the progression, metastatic dissemination, and therapy resistance in breast cancers.

The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure.

Ozone (O) is a natural, highly unstable atmospheric gas that rapidly decomposes to oxygen. Although not being a radical molecule, O is a very strong oxidant and therefore it is potentially toxic for living organisms. However, scientific evidence proved that the effects of O exposure are dose-dependent: high dosages stimulate severe oxidative stress resulting in inflammatory response and tissue injury, whereas low O concentrations induce a moderate oxidative eustress activating antioxidant pathways.

The arrhinias: Proboscis lateralis literature review and surgical update.

Proboscis lateralis (PL) is a rare malformation, reported for the first time in 1861 by Forster in his monograph on congenital malformations of the human body. The abnormal side of the nose is represented by a tube-like rudimentary nasal structure, attached at any point along the embryonic fusion line between the anterior maxilla and the frontonasal processes. As clefts of the lip (and alveolus) are bilateral or unilateral, an arrhinia can be bilateral (total) or unilateral.