Neuroblastoma-derived hypoxic extracellular vesicles promote metastatic dissemination in a zebrafish model.

The zebrafish (Danio rerio) is a valuable model organism for studying human biology due to its easy genetic manipulation and small size. It is optically transparent and shares genetic similarities with humans, making it ideal for studying developmental processes, diseases, and drug screening via imaging-based approaches. Solid malignant tumors often contain hypoxic areas that stimulate the release of extracellular vesicles (EVs), lipid-bound structures released by cells into the extracellular space, that facilitate short- and long-range intercellular communication and metastatization.

DNA repair-dependent immunogenic liabilities in colorectal cancer: opportunities from errors.

Colorectal cancer (CRC) remains one of the major causes of cancer death worldwide. Chemotherapy continues to serve as the primary treatment modality, while immunotherapy is largely ineffective for the majority of CRC patients. Seminal discoveries have emphasized that modifying DNA damage response (DDR) mechanisms confers both cell-autonomous and immune-related vulnerabilities across various cancers.

Ultrasound Examination of Common Carotid Adventitial Thickness Can Differentiate Takayasu Arteritis and Large Vessel Giant Cell Arteritis.

Pathological studies have demonstrated that the adventitial layer is markedly thickened in Takayasu (TAK) as compared to large vessel giant cell arteritis (LV-GCA). An ultrasound (US) examination of the arterial vessels allows the determination of intima media thickness (IMT) and of adventitial layer thickness (extra media thickness (EMT)). No previous study has evaluated if there are differences in EMT thickness between TAK and LV-GCA.

Variation of total alpha and beta activities and Rn-222 concentrations in the water supply system of an Italian volcanic region: How safe is tap water for human consumption?

Total alpha and beta activities and Rn-222 concentrations were determined in water from different sections of seven aqueducts belonging to the water supply system of Campania region (Italy), known worldwide for its volcanism. Statistical analysis was performed on data to account for their variability across the aqueduct sections, and results were discussed considering the geology of reservoirs, the potential mixing processes occurring along the pipe network, the building/constituting materials of the aqueduct sections, and the integrity of the infrastructure. Guidelines proposed by Italian and international regulation entities were considered to determine if total alpha and beta activities and Rn-222 concentrations found at the taps of the different aqueducts should be considered detrimental to public health.

Dendritic cell-targeted therapy expands CD8 T cell responses to bona-fide neoantigens in lung tumors.

Cross-presentation by type 1 DCs (cDC1) is critical to induce and sustain antitumoral CD8 T cell responses to model antigens, in various tumor settings. However, the impact of cross-presenting cDC1 and the potential of DC-based therapies in tumors carrying varied levels of bona-fide neoantigens (neoAgs) remain unclear. Here we develop a hypermutated model of non-small cell lung cancer in female mice, encoding genuine MHC-I neoepitopes to study neoAgs-specific CD8 T cell responses in spontaneous settings and upon Flt3L + αCD40 (DC-therapy).

Non-canonical antigens are the largest fraction of peptides presented by MHC class I in mismatch repair deficient murine colorectal cancer.

Background: Immunotherapy based on checkpoint inhibitors is highly effective in mismatch repair deficient (MMRd) colorectal cancer (CRC). These tumors carry a high number of mutations, which are predicted to translate into a wide array of neoepitopes; however, a systematic classification of the neoantigen repertoire in MMRd CRC is lacking. Mass spectrometry peptidomics has demonstrated the existence of MHC class I associated peptides (MAPs) originating from non-coding DNA regions.

miR-210-3p enriched extracellular vesicles from hypoxic neuroblastoma cells stimulate migration and invasion of target cells.

Background: Tumor hypoxia stimulates release of extracellular vesicles (EVs) that facilitate short- and long-range intercellular communication and metastatization. Albeit hypoxia and EVs release are known features of Neuroblastoma (NB), a metastasis-prone childhood malignancy of the sympathetic nervous system, whether hypoxic EVs can facilitate NB dissemination is unclear.

Methods: Here we isolated and characterized EVs from normoxic and hypoxic NB cell culture supernatants and performed microRNA (miRNA) cargo analysis to identify key mediators of EVs biological effects.

Unique Patterns of Heterogeneous Mismatch Repair Protein Expression in Colorectal Cancer Unveil Different Degrees of Tumor Mutational Burden and Distinct Tumor Microenvironment Features.

Mismatch repair (MMR) protein expression in colorectal cancer (CRC) cells is usually homogeneously retained or lost. Rare lesions may show a heterogeneous pattern of MMR protein expression. We evaluated MMR protein expression (MLH1, MSH2, MSH6, and PMS2) in 200 CRCs, identifying 3 groups with proficient MMR protein expression (MMRp), deficient MMR protein expression (MMRd), and heterogeneous MMR protein expression (MMRh).

Handwriting fluency, latency, and kinematic in Portuguese writing system: Pilot study with school children from 3rd to 5th grade.

Studies have referred to the interaction between orthographic and motor aspects during the production of handwriting. However, studies with Brazilian Portuguese are still lacking. Hence, the aim of this study was to compare orthographic regularity, based on the Portuguese writing system, in high (HF) and low (LF) frequency words, in relation to latency and kinematic variables in students from the 3rd to the 5th grade of elementary school.

Ultrasmall Folate Receptor Alpha Targeted Enzymatically Cleavable Silica Nanoparticle Drug Conjugates Augment Penetration and Therapeutic Efficacy in Models of Cancer.

To address the key challenges in the development of next-generation drug delivery systems (DDS) with desired physicochemical properties to overcome limitations regarding safety, in vivo efficacy, and solid tumor penetration, an ultrasmall folate receptor alpha (FRα) targeted silica nanoparticle (C'Dot) drug conjugate (CDC; or folic acid CDC) was developed. A broad array of methods was employed to screen a panel of CDCs and identify a lead folic acid CDC for clinical development. These included comparing the performance against antibody-drug conjugates (ADCs) in three-dimensional tumor spheroid penetration ability, assessing in vitro/ex vivo cytotoxic efficacy, as well as in vivo therapeutic outcome in multiple cell-line-derived and patient-derived xenograft models.

Ultrasound response to tofacitinib in patients with rheumatoid arthritis: Data from a multicenter 24 weeks prospective study.

Background: Treatment of rheumatoid arthritis (RA) should aim at full remission. Ultrasonography (US) might have an added value to clinical examination in assessing disease activity of RA. In this study we evaluated the ultrasound response, next to clinical and laboratory response, in RA patients treated with tofacitinib (TOF).

Parasitism of Nelore (Bos indicus) calf from northern Brazil by Ctenocephalides felis.

Ctenocephalides felis is the most common hematophagous ectoparasite of domestic cats and dogs worldwide, causing allergic dermatitis, anemia, itching, discomfort, and it is responsible for the transmission of many pathogens. In cattle, parasitism is not common but occurs due to the high adaptability of this flea species. This study aimed to report infestation of a Nellore (Bos indicus) calf from Northern Brazil by C.

Association of CD209 (DC-SIGN) rs735240 SNV with paucibacillary leprosy in the Brazilian population and its functional effects.

Background: Leprosy, caused by Mycobacterium leprae, is a public health problem in Brazil that affects peripheral nerves, resulting in physical disabilities. During host-pathogen interactions, the immune response determines leprosy outcomes from a localised (paucibacillary) form to a disseminated (multibacillary) form. The recognition of M.

Temozolomide Treatment Alters Mismatch Repair and Boosts Mutational Burden in Tumor and Blood of Colorectal Cancer Patients.

Unlabelled: The majority of metastatic colorectal cancers (mCRC) are mismatch repair (MMR) proficient and unresponsive to immunotherapy, whereas MMR-deficient (MMRd) tumors often respond to immune-checkpoint blockade. We previously reported that the treatment of colorectal cancer preclinical models with temozolomide (TMZ) leads to MMR deficiency, increased tumor mutational burden (TMB), and sensitization to immunotherapy. To clinically translate these findings, we designed the ARETHUSA clinical trial whereby O6-methylguanine-DNA-methyltransferase (MGMT)-deficient, MMR-proficient, RAS-mutant mCRC patients received priming therapy with TMZ.

Experiences of distortions to the passage of time during the Argentinian Covid-19 pandemic.

The Coronavirus-19 global pandemic has forced many governments around the world to enforce "lockdowns" to curtail the spread of the virus. Studies conducted in the UK, France, Italy and Brazil have demonstrated that one consequence of these lockdowns is significant distortion to the speed of the passage of time. The current study sought to establish how the passage of time was experienced during the Argentinian lockdown.

The long non-coding RNA overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics.

Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified the long non-coding RNA able to cluster an AML subgroup with peculiar gene signatures linked to hematopoietic cell differentiation and mitochondrial dynamics. silencing triggered hematopoietic commitment in healthy CD34+ cells, whereas in AML cells the pathological undifferentiated state was rescued.

Mechanisms of Immune Escape and Resistance to Checkpoint Inhibitor Therapies in Mismatch Repair Deficient Metastatic Colorectal Cancers.

Immune checkpoint inhibitors (CPIs) represent an effective therapeutic strategy for several different types of solid tumors and are remarkably effective in mismatch repair deficient (MMRd) tumors, including colorectal cancer (CRC). The prevalent view is that the elevated and dynamic neoantigen burden associated with the mutator phenotype of MMRd fosters enhanced immune surveillance of these cancers. In addition, recent findings suggest that MMRd tumors have increased cytosolic DNA, which triggers the cGAS STING pathway, leading to interferon-mediated immune response.

Aquaporins Are Differentially Regulated in Canine Cryptorchid Efferent Ductules and Epididymis.

The efferent ductules and the epididymis are parts of the male reproductive system where spermatozoa mature. Specialized epithelial cells in these ducts contribute to the transport of fluids produced by spermatozoa's metabolic activity. Aquaporins (AQPs) have been demonstrated to be expressed in the spermatozoan membrane and testis epithelial cells, where they contribute to regulating spermatozoan volume and transit through environments of differing osmolality.

T Cells Expressing Receptor Recombination/Revision Machinery Are Detected in the Tumor Microenvironment and Expanded in Genomically Over-unstable Models.

Tumors undergo dynamic immunoediting as part of a process that balances immunologic sensing of emerging neoantigens and evasion from immune responses. Tumor-infiltrating lymphocytes (TIL) comprise heterogeneous subsets of peripheral T cells characterized by diverse functional differentiation states and dependence on T-cell receptor (TCR) specificity gained through recombination events during their development. We hypothesized that within the tumor microenvironment (TME), an antigenic milieu and immunologic interface, tumor-infiltrating peripheral T cells could reexpress key elements of the TCR recombination machinery, namely, Rag1 and Rag2 recombinases and Tdt polymerase, as a potential mechanism involved in the revision of TCR specificity.

Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in -Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection.

Leprosy is a disease with a clinical spectrum of presentations that is also manifested in diverse histological features. At one pole, lepromatous lesions (L-pole) have phagocytic foamy macrophages heavily parasitized with freely multiplying intracellular . At the other pole, the presence of epithelioid giant cells and granulomatous formation in tuberculoid lesions (T-pole) lead to the control of replication and the containment of its spread.

CD4 T Cell-Dependent Rejection of Beta-2 Microglobulin Null Mismatch Repair-Deficient Tumors.

Inactivation of beta-2 microglobulin (B2M) is considered a determinant of resistance to immune checkpoint inhibitors (ICPi) in melanoma and lung cancers. In contrast, loss does not appear to affect response to ICPis in mismatch repair-deficient (MMRd) colorectal tumors where biallelic inactivation of is frequently observed. We inactivated in multiple murine MMRd cancer models.

Muscle functional recovery is driven by extracellular vesicles combined with muscle extracellular matrix in a volumetric muscle loss murine model.

Biological scaffolds derived from decellularized tissues are being investigated as a promising approach to repair volumetric muscle losses (VML). Indeed, extracellular matrix (ECM) from decellularized tissues is highly biocompatible and mimics the original tissue. However, the development of fibrosis and the muscle stiffness still represents a major problem.

Salivary Gland Ultrasonography in Sjögren's Syndrome: A European Multicenter Reliability Exercise for the HarmonicSS Project.

Salivary gland ultrasonography (SGUS) is increasingly applied for the management of primary Sjögren's syndrome (pSS). This study aims to: (i) compare the reliability between two SGUS scores; (ii) test the reliability among sonographers with different levels of experience. In the reliability exercise, two four-grade semi-quantitative SGUS scoring systems, namely De Vita et al.