The dark side of the fibroblastic sleeve: Case report and literature review.

The fibroblastic sleeve is a structure potentially enveloping any intravascular device. At ultrasound scan, it typically presents as a thin layer of variably echogenic material covering the catheter surface, which usually tends to remain into the vessel after the catheter removal. However, several case reports have documented its migration toward the heart or pulmonary artery after a central venous catheter removal.

Management of Type III Intrathyroidal Parathyroid Adenomas By Enucleation: Case Report and Literature Review.

Parathyroid adenoma is a common endocrine disorder, but its intrathyroid presentation is relatively rare. The traditional approach, such as thyroid blind lobectomy, is the most frequent modality of treatment due to the possible unclear localization of the adenoma in the preoperative workup. This increases the risk of unnecessary probability of hypothyroidism.

High level of circulating cell-free tumor DNA at diagnosis correlates with disease spreading and defines multiple myeloma patients with poor prognosis.

Multiple myeloma (MM) is a plasma cell (PC) disorder characterized by skeletal involvement at the time of diagnosis. Recently, cell-free DNA (cfDNA) has been proven to recapitulate the heterogeneity of bone marrow (BM) disease. Our aim was to evaluate the prognostic role of cfDNA at diagnosis according to disease distribution, and to investigate the role of the MM microenvironment inflammatory state in supplying the release of cfDNA.

Small heat shock protein B8: from cell functions to its involvement in diseases and potential therapeutic applications.

Heat shock protein family B (small) member 8 (HSPB8) is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins. HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation, cell division, and migration. HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.

Tracking Response and Resistance in Acute Myeloid Leukemia through Single-Cell DNA Sequencing Helps Uncover New Therapeutic Targets.

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasia with a complex polyclonal architecture. Among driver lesions, those involving the gene represent the most frequent mutations identified at diagnosis. The development of tyrosine kinase inhibitors (TKIs) has improved the clinical outcomes of -mutated patients (Pt).

Altered molecular and cellular mechanisms in KIF5A-associated neurodegenerative or neurodevelopmental disorders.

Mutations targeting distinct domains of the neuron-specific kinesin KIF5A associate with different neurodegenerative/neurodevelopmental disorders, but the molecular bases of this clinical heterogeneity are unknown. We characterised five key mutants covering the whole spectrum of KIF5A-related phenotypes: spastic paraplegia (SPG, R17Q and R280C), Charcot-Marie-Tooth disease (CMT, R864*), amyotrophic lateral sclerosis (ALS, N999Vfs*40), and neonatal intractable myoclonus (NEIMY, C975Vfs*73) KIF5A mutants. CMT-R864*-KIF5A and ALS-N999Vfs*40-KIF5A showed impaired autoinhibition and peripheral localisation accompanied by altered mitochondrial distribution, suggesting transport competence disruption.

Colchicine treatment in amyotrophic lateral sclerosis: safety, biological and clinical effects in a randomized clinical trial.

In preclinical studies, the anti-inflammatory drug colchicine, which has never been tested in amyotrophic lateral sclerosis, enhanced the expression of autophagy factors and inhibited accumulation of transactive response DNA-binding protein 43 kDa, a known histopathological marker of amyotrophic lateral sclerosis. This multicentre, randomized, double-blind trial enrolled patients with probable or definite amyotrophic lateral sclerosis who experienced symptom onset within the past 18 months. Patients were randomly assigned in a 1:1:1 ratio to receive colchicine at a dose of 0.

Circulating Multiple Myeloma Cells (CMMCs) as Prognostic and Predictive Markers in Multiple Myeloma and Smouldering MM Patients.

In recent years, liquid biopsy has emerged as a promising alternative to the bone marrow (BM) examination, since it is a minimally invasive technique allowing serial monitoring. Circulating multiple myeloma cells (CMMCs) enumerated using CELLSEARCH were correlated with patients' prognosis and measured under treatment to assess their role in monitoring disease dynamics. Forty-four MM and seven smouldering MM (SMM) patients were studied.

Lysosome quality control in health and neurodegenerative diseases.

Lysosomes are acidic organelles involved in crucial intracellular functions, including the degradation of organelles and protein, membrane repair, phagocytosis, endocytosis, and nutrient sensing. Given these key roles of lysosomes, maintaining their homeostasis is essential for cell viability. Thus, to preserve lysosome integrity and functionality, cells have developed a complex intracellular system, called lysosome quality control (LQC).

Sunitinib-mediated inhibition of STAT3 in skeletal muscle and spinal cord does not affect the disease in a mouse model of ALS.

Variability in disease onset and progression is a hallmark of amyotrophic lateral sclerosis (ALS), both in sporadic and genetic forms. Recently, we found that SOD1-G93A transgenic mice expressing the same amount of mutant SOD1 but with different genetic backgrounds, C57BL/6JOlaHsd and 129S2/SvHsd, show slow and rapid muscle wasting and disease progression, respectively. Here, we investigated the different molecular mechanisms underlying muscle atrophy.

Single-Cell DNA Sequencing Reveals an Evolutionary Pattern of CHIP in Transplant Eligible Multiple Myeloma Patients.

Clonal hematopoiesis of indeterminate potential (CHIP) refers to the phenomenon where a hematopoietic stem cell acquires fitness-increasing mutation(s), resulting in its clonal expansion. CHIP is frequently observed in multiple myeloma (MM) patients, and it is associated with a worse outcome. High-throughput amplicon-based single-cell DNA sequencing was performed on circulating CD34+ cells collected from twelve MM patients before autologous stem cell transplantation (ASCT).

Manzamine A reduces androgen receptor transcription and synthesis by blocking E2F8-DNA interactions and effectively inhibits prostate tumor growth in mice.

The androgen receptor (AR) is the main driver in the development of castration-resistant prostate cancer, where the emergence of AR splice variants leads to treatment-resistant disease. Through detailed molecular studies of the marine alkaloid manzamine A (MA), we identified transcription factor E2F8 as a previously unknown regulator of AR transcription that prevents AR synthesis in prostate cancer cells. MA significantly inhibited the growth of various prostate cancer cell lines and was highly effective in inhibiting xenograft tumor growth in mice without any pathophysiological perturbations in major organs.

Multi-dimensional scaling techniques unveiled gain1q&loss13q co-occurrence in Multiple Myeloma patients with specific genomic, transcriptional and adverse clinical features.

The complexity of Multiple Myeloma (MM) is driven by several genomic aberrations, interacting with disease-related and/or -unrelated factors and conditioning patients' clinical outcome. Patient's prognosis is hardly predictable, as commonly employed MM risk models do not precisely partition high- from low-risk patients, preventing the reliable recognition of early relapsing/refractory patients. By a dimensionality reduction approach, here we dissect the genomic landscape of a large cohort of newly diagnosed MM patients, modelling all the possible interactions between any MM chromosomal alterations.

High levels of CRBN isoform lacking IMiDs binding domain predicts for a worse response to IMiDs-based upfront therapy in newly diagnosed myeloma patients.

In recent years, the immunoderivative (IMiD) agents have been extensively used for the treatment of multiple myeloma (MM). IMiDs and their newer derivatives CRBN E3 ligase modulator bind the E3 ligase substrate recognition adapter protein cereblon (CRBN), which has been recognized as one of the IMiDs' direct target proteins, and it is essential for the therapeutic effect of these agents.High expression of CRBN was associated with improved clinical response in patients with MM treated with IMiDs, further confirming that the expression of IMiDs' direct target protein CRBN is required for the anti-MM activity.

Long term follow-up of humoral and cellular response to mRNA-based vaccines for SARS-CoV-2 in patients with active multiple myeloma.

Long-term kinetics of antibody (Ab) and cell-mediated immune (CMI) response to full anti-SARS-CoV-2 vaccine schedule and booster doses in Multiple Myeloma (MM) patients remain unclear. We prospectively evaluated Ab and CMI response to mRNA vaccines in 103 SARS-CoV-2-naïve MM patients (median age 66, 1 median prior line of therapy) and 63 health-workers. Anti-S-RBD IgG (Elecsysassay) were measured before vaccination and after 1 (T1), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months from second dose (D2) and 1 month after the introduction of the booster dose (T1D3).

HSPB8 frameshift mutant aggregates weaken chaperone-assisted selective autophagy in neuromyopathies.

Chaperone-assisted selective autophagy (CASA) is a highly selective pathway for the disposal of misfolding and aggregating proteins. In muscle, CASA assures muscle integrity by favoring the turnover of structural components damaged by mechanical strain. In neurons, CASA promotes the removal of aggregating substrates.

Bicalutamide and Trehalose Ameliorate Spinal and Bulbar Muscular Atrophy Pathology in Mice.

Spinal and bulbar muscular atrophy (SBMA) is characterized by motor neuron (MN) degeneration that leads to slowly progressive muscle weakness. It is considered a neuromuscular disease since muscle has a primary role in disease onset and progression. SBMA is caused by a CAG triplet repeat expansion in the androgen receptor (AR) gene.

The chaperone-assisted selective autophagy complex dynamics and dysfunctions.

Each protein must be synthesized with the correct amino acid sequence, folded into its native structure, and transported to a relevant subcellular location and protein complex. If any of these steps fail, the cell has the capacity to break down aberrant proteins to maintain protein homeostasis (also called proteostasis). All cells possess a set of well-characterized protein quality control systems to minimize protein misfolding and the damage it might cause.

Identification of HSPB8 modulators counteracting misfolded protein accumulation in neurodegenerative diseases.

Aims: The small Heat Shock Protein B8 (HSPB8) is the core component of the Chaperone-Assisted Selective Autophagy (CASA) complex. This complex selectively targets, transports, and tags misfolded proteins for their recognition by autophagy receptors and insertion into the autophagosome for clearance. CASA is essential to maintain intracellular proteostasis, especially in heart, muscle, and brain often exposed to various types of cell stresses.

HSPB8 counteracts tumor activity of BRAF- and NRAS-mutant melanoma cells by modulation of RAS-prenylation and autophagy.

Cutaneous melanoma is one of the most aggressive and lethal forms of skin cancer. Some specific driver mutations have been described in multiple oncogenes including BRAF and NRAS that are mutated in 60-70% and 15-20% of melanoma, respectively. The aim of this study was to evaluate the role of Small Heat Shock Protein B8 (HSPB8) on cell growth and migration of both BLM (BRAF/NRAS) and A375 (BRAF/NRAS) human melanoma cell lines.

Identification of a Maturation Plasma Cell Index through a Highly Sensitive Droplet Digital PCR Assay Gene Expression Signature Validation in Newly Diagnosed Multiple Myeloma Patients.

DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile.

The : How to define the hemodilution of bone marrow samples in lymphoproliferative diseases.

Introduction: Minimal residual disease (MRD) is commonly assessed in bone marrow (BM) aspirate. However, sample quality can impair the MRD measurement, leading to underestimated residual cells and to false negative results. To define a reliable and reproducible method for the assessment of BM hemodilution, several flow cytometry (FC) strategies for hemodilution evaluation have been compared.

The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases.

Motoneuron diseases (MNDs) are neurodegenerative conditions associated with death of upper and/or lower motoneurons (MNs). Proteostasis alteration is a pathogenic mechanism involved in many MNDs and is due to the excessive presence of misfolded and aggregated proteins. Protein misfolding may be the product of gene mutations, or due to defects in the translation process, or to stress agents; all these conditions may alter the native conformation of proteins making them prone to aggregate.

The role of autophagy-lysosomal pathway in motor neuron diseases.

Motor neuron diseases (MNDs) include a broad group of diseases in which neurodegeneration mainly affects upper and/or lower motor neurons (MNs). Although the involvement of specific MNs, symptoms, age of onset, and progression differ in MNDs, the main pathogenic mechanism common to most MNDs is represented by proteostasis alteration and proteotoxicity. This pathomechanism may be directly related to mutations in genes encoding proteins involved in the protein quality control system, particularly the autophagy-lysosomal pathway (ALP).

: A copy number clustering tool designed to refit and recalibrate the baseline region of tumors' profiles.

Human cancer arises from a population of cells that have acquired a wide range of genetic alterations, most of which are targets of therapeutic treatments or are used as prognostic factors for patient's risk stratification. Among these, copy number alterations (CNAs) are quite frequent. Currently, several molecular biology technologies, such as microarrays, NGS and single-cell approaches are used to define the genomic profile of tumor samples.