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1.
Sci Rep ; 14(1): 16146, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997412

RESUMEN

A circular polarized (CP) pentaband antenna based on the aperture-in-aperture (AIA) concept is presented for CubeSat applications. This AIA consists of five different bands ranging from L-band to Ka-band. Four different antennas, each operating at a specific frequency band, namely 12 GHz, 18.5 GHz, 26 GHz, and 32 GHz, were incorporated into an L-band (viz. 1.5 GHz) antenna. Notably, the five antennas can operate simultaneously for a CubeSat downlink operation with a frequency ratio of 21.3:1. The antenna structure shows a realized gain of 5-10 dBi with good CP bandwidth (< 3 dB) across the overall operational frequency range. That is, the realized gain of L-band (1.5 GHz), X-band (12.5 GHz), K-band1 (18.5 GHz), K-band2 (26 GHz), and Ka-bands (32 GHz) are 5.05 dBi, 8.21 dBi, 7.33 dBi, 7.97 dBi, and 8.56 dBi. A high impedance surface (HIS) is incorporated with the Ka-band antenna to mitigate the ripples in the radiation pattern created by the interference of surface waves. A prototype was fabricated and tested. The measurement data agrees well with the simulation.

2.
Am J Clin Dermatol ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38907174

RESUMEN

Uveal melanoma (UM) is genetically a distinct tumor compared to cutaneous melanoma (CM), and due to its low mutational burden, it is far less perceptible to the immune system. Thus, treatments that have revolutionized the treatment of CM remain widely inefficient in metastatic UM or only demonstrate effectiveness in a small subpopulation of patients. To this end, the therapeutic benefit of immune checkpoint blockade is very limited and may come at the expense of severe immune-related adverse events that could potentially affect all organ systems. Notably, tebentafusp, an entirely novel class of anti-cancer drugs, has received official authorization for the treatment of metastatic UM. It is the first agent that demonstrated a survival advantage in a randomized controlled trial of metastatic UM patients. Despite the survival benefit and approval, the restriction of tebentafusp to HLA-A*02:01-positive patients and the low objective response rate indicate the persistent need for additional therapies. Thus, liver-directed therapies are commonly used for tumor control of hepatic metastases and represent a central pillar of the daily management of liver-dominant disease. Further, promising data from targeted therapies independent of MEK-inhibitors, such as the combination of darovasertib and crizotinib, raise hope for additional options in metastatic UM in the future. This narrative review provides a timely and comprehensive overview of the current treatment landscape for metastatic UM.

3.
World Neurosurg ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901475

RESUMEN

BACKGROUND: Ultrasound imaging is inexpensive, portable, and widely available. The development of a real-time transcutaneous spinal cord perfusion monitoring system would allow more precise targeting of mean arterial pressure goals following acute spinal cord injury (SCI). There has been no prior demonstration of successful real-time cord perfusion monitoring in humans. METHODS: Four adult patients who had undergone posterior cervical decompression and instrumentation at a single center were enrolled into this prospective feasibility study. All participants had undergone cervical laminectomies spanning ≥2 contiguous levels ≥2 months prior to inclusion with no history of SCI. The first 2 underwent transcutaneous ultrasound without contrast and the second 2 underwent contrast-enhanced ultrasound (CEUS) with intravenously injected microbubble contrast. RESULTS: Using noncontrast ultrasound with or without Doppler (n = 2), the dura, spinal cord, and vertebral bodies were apparent however ultrasonography was insufficient to discern intramedullary perfusion or clear white-gray matter differentiation. With application of microbubble contrast (n = 2), it was possible to quantify differential spinal cord perfusion within and between cross-sectional regions of the cord. Further, it was possible to quantify spinal cord hemodynamic perfusion using CEUS by measuring peak signal intensity and the time to peak signal intensity after microbubble contrast injection. Time-intensity curves were generated and area under the curves were calculated as a marker of tissue perfusion. CONCLUSIONS: CEUS is a viable platform for monitoring real-time cord perfusion in patients who have undergone prior cervical laminectomies. Further development has the potential to change clinical management acute SCI by tailoring treatments to measured tissue perfusion parameters.

4.
ChemMedChem ; : e202400416, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38887174

RESUMEN

STING agonists are potent enhancers of a pro-inflammatory response and, thus, potentially useful therapeutics. Unfortunately, many agonists developed to date require complex drug delivery formulations and often have poor water solubility, limiting their use for systemic administration. Here, we report the discovery and chemical characterization of lactones of MSA-2 as new STING prodrugs with enhanced properties. We show that these prodrugs form efficient inclusion complexes with tumor myeloid cell targeting cyclodextrin nanoparticles and propose a new mechanism of formation and hydrolysis.

5.
Rev Med Interne ; 45(6): 354-365, 2024 Jun.
Artículo en Francés | MEDLINE | ID: mdl-38823999

RESUMEN

Catheter-related thrombosis (CRT) is a relatively frequent and potentially fatal complication arising in patients with cancer who require a central catheter placement for intravenous treatment. In everyday practice, CRT remains a challenge for management; despite its frequency and its negative clinical impact, few data are available concerning diagnosis and treatment of CRT. In particular, no diagnostic studies or clinical trials have been published that included exclusively patients with cancer and a central venous catheter (CVC). For this reason, many questions regarding optimal management of CRT remain unanswered. Due to the paucity of high-grade evidence regarding CRT in cancer patients, guidelines are derived from upper extremity DVT studies for diagnosis, and from those for lower limb DVT for treatment. This article addresses the issues of diagnosis and management of CRT through a review of the available literature and makes a number of proposals based on the available evidence. In symptomatic patients, venous ultrasound is the most appropriate choice for first-line diagnostic imaging of CRT because it is noninvasive, and its diagnostic performance is high (which is not the case in asymptomatic patients). In the absence of direct comparative clinical trials, we suggest treating patients with CRT with a therapeutic dose of either a LMWH or a direct oral factor Xa inhibitor, with or without a loading dose. These anticoagulants should be given for a total of at least 3 months, including at least 1 month after catheter removal following initiation of therapy.


Asunto(s)
Cateterismo Venoso Central , Neoplasias , Trombosis Venosa Profunda de la Extremidad Superior , Humanos , Neoplasias/complicaciones , Trombosis Venosa Profunda de la Extremidad Superior/diagnóstico , Trombosis Venosa Profunda de la Extremidad Superior/terapia , Trombosis Venosa Profunda de la Extremidad Superior/etiología , Cateterismo Venoso Central/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación
6.
Front Immunol ; 15: 1395225, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915414

RESUMEN

Introduction: Despite recent advancements in the treatment of metastatic uveal melanoma (UM), the availability of further treatment options remains limited and the prognosis continues to be poor in many cases. In addition to tebentafusp, immune checkpoint blockade (ICB, PD-1 (+/-) CTLA-4 antibodies) is commonly used for metastatic UM, in particular in HLA-A 02:01-negative patients. However, ICB comes at the cost of potentially severe immune-related adverse events (irAE). Thus, the selection of patient groups that are more likely to benefit from ICB is desirable. Methods: In this analysis, 194 patients with metastatic UM undergoing ICB were included. Patients were recruited from German skin cancer sites and the ADOReg registry. To investigate the association of irAE occurrence with treatment response, progression-free survival (PFS), and overall survival (OS) two cohorts were compared: patients without irAE or grade 1/2 irAE (n=137) and patients with grade 3/4 irAE (n=57). Results: In the entire population, the median OS was 16.4 months, and the median PFS was 2.8 months. Patients with grade 3/4 irAE showed more favorable survival than patients without or grade 1/2 irAE (p=0.0071). IrAE occurred in 44.7% (87/194), and severe irAE in 29.4% (57/194) of patients. Interestingly, irColitis and irHepatitis were significantly associated with longer OS (p=0.0031 and p=0.011, respectively). Conclusions: This data may indicate an association between irAE and favorable survival outcomes in patients with metastatic UM undergoing ICB treatment and suggests that a reduced tolerance to tumor antigens could be linked to reduced tolerance to self-antigens.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Melanoma , Neoplasias de la Úvea , Humanos , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/tratamiento farmacológico , Neoplasias de la Úvea/inmunología , Neoplasias de la Úvea/patología , Melanoma/tratamiento farmacológico , Melanoma/mortalidad , Melanoma/inmunología , Masculino , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Femenino , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Metástasis de la Neoplasia
7.
J Vasc Interv Radiol ; 35(8): 1154-1165.e6, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38729421

RESUMEN

PURPOSE: To report the first interim analysis of the STRIKE-PE study, evaluating the safety and effectiveness of computer assisted vaccum thrombectomy (CAVT) for the treatment of acute pulmonary embolism (PE). MATERIALS AND METHODS: This prospective, international, multicenter study will enroll 600 adult patients with acute PE of ≤14 days and a right ventricle (RV)-to-left ventricle (LV) ratio of ≥0.9 who receive first-line endovascular treatment with CAVT using the Indigo Aspiration System (Penumbra, Alameda, California). Primary endpoints are change in RV/LV ratio and incidence of composite major adverse events (MAEs) within 48 hours. Secondary endpoints include functional and quality-of-life (QoL) assessments. RESULTS: The first 150 consecutive patients were treated with 12F catheter CAVT. Mean age was 61.3 years, 54.7% were men, 94.7% presented with intermediate-risk PE, and 5.3% presented with high-risk PE. Median thrombectomy and procedure times were 33.5 minutes and 70.0 minutes, respectively, resulting in a mean reduction in systolic pulmonary artery pressure of 16.3% (P < .001). Mean RV/LV ratio decreased from 1.39 to 1.01 at 48 hours, a 25.7% reduction (P < .001). Four (2.7%) patients experienced a composite MAE within 48 hours. At 90-day follow-up, patients exhibited statistically significant improvements in the Borg dyspnea scale score and QoL measures, and the New York Heart Association class distribution returned to that reported before the index PE. CONCLUSIONS: Interim results from the STRIKE-PE study demonstrate a significant reduction in pulmonary artery pressure and RV/LV ratio, a median thrombectomy time of 33.5 minutes, a composite MAE rate of 2.7%, and significant improvements in 90-day functional and QoL outcomes.


Asunto(s)
Embolia Pulmonar , Calidad de Vida , Trombectomía , Humanos , Femenino , Masculino , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/terapia , Embolia Pulmonar/cirugía , Persona de Mediana Edad , Trombectomía/efectos adversos , Trombectomía/instrumentación , Resultado del Tratamiento , Estudios Prospectivos , Anciano , Factores de Tiempo , Recuperación de la Función , Adulto , Vacio , Estado Funcional , Factores de Riesgo
8.
Cureus ; 16(4): e59065, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38800139

RESUMEN

Intracranial subdural empyema is a loculated collection of pus in the subdural space between the dura mater and the arachnoid that can be life-threatening. Here, we present a case of a 22-year-old man hospitalized for management of sepsis due to right orbital cellulitis who experienced sudden-onset right-sided hemiplegia and was found to have a holohemispheric intracranial subdural empyema requiring emergent neurosurgical intervention. Subdural empyemas are commonly caused by maxillofacial infections, including orbital infections. We demonstrate that orbital cellulitis may cause an intracranial subdural empyema that can present with sudden-onset neurological deficits warranting prompt neurosurgical intervention.

9.
Rev Med Interne ; 45(5): 289-299, 2024 May.
Artículo en Francés | MEDLINE | ID: mdl-38806295

RESUMEN

Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain anticancer drugs on haemostasis. This is true both for first episode venous thromboembolism and recurrence. The diagnosis and management of VTE recurrence in patients with cancer poses particular challenges, and these are reviewed in the present article, based on a systematic review of the relevant scientific literature published over the last decade. Furthermore, it is uncertain whether diagnostic algorithms for venous thromboembolism, validated principally in untreated non-cancer patients, are also valid in anticoagulated cancer patients: the available data suggests that clinical decision rules and D-dimer testing perform less well in this clinical setting. In patients with cancer, computed tomography pulmonary angiography and venous ultrasound appear to be the most reliable diagnostic tools for diagnosis of pulmonary embolism and deep vein thrombosis respectively. Options for treatment of venous thromboembolism include low molecular weight heparins (at a therapeutic dose or an increased dose), fondaparinux or oral direct factor Xa inhibitors. The choice of treatment should take into account the nature (pulmonary embolism or VTE) and severity of the recurrent event, the associated bleeding risk, the current anticoagulant treatment (type, dose, adherence and possible drug-drug interactions) and cancer progression.


Asunto(s)
Anticoagulantes , Neoplasias , Recurrencia , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/tratamiento farmacológico , Neoplasias/complicaciones , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Francia/epidemiología
10.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38731877

RESUMEN

Epstein-Barr virus (EBV) DNA is known to be shed upon reactivation of latent EBV. Based on our previous findings linking Toll-like receptor-9 (TLR9) to an EBV DNA-driven surge in IL-17A production, we aimed to examine the therapeutic potential of TLR9 inhibition in EBV DNA-exacerbated arthritis in a collagen-induced arthritis (CIA) mouse model. C57BL/6J mice were administered either collagen, EBV DNA + collagen, EBV DNA + collagen + TLR9 inhibitor, or only the TLR9 inhibitor. After 70 days, paw thicknesses, clinical scores, and gripping strength were recorded. Moreover, affected joints, footpads, and colons were histologically scored. Furthermore, the number of cells co-expressing IL-17A, IFN-γ, and FOXP3 in joint sections was determined by immunofluorescence assays. Significantly decreased paw thicknesses, clinical scores, and histological scores with a significantly increased gripping strength were observed in the group receiving EBV DNA + collagen + TLR9 inhibitor, compared to those receiving EBV DNA + collagen. Similarly, this group showed decreased IL-17A+ IFN-γ+, IL-17A+ FOXP3+, and IL-17A+ IFN-γ+ FOXP3+ foci counts in joints. We show that inhibiting TLR9 limits the exacerbation of arthritis induced by EBV DNA in a CIA mouse model, suggesting that TLR9 could be a potential therapeutic target for rheumatoid arthritis management in EBV-infected individuals.


Asunto(s)
Artritis Experimental , ADN Viral , Modelos Animales de Enfermedad , Herpesvirus Humano 4 , Receptor Toll-Like 9 , Animales , Ratones , Artritis Experimental/virología , Artritis Experimental/patología , Artritis Experimental/metabolismo , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Artritis Reumatoide/virología , ADN Viral/genética , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4/fisiología , Interleucina-17/metabolismo , Ratones Endogámicos C57BL , Receptor Toll-Like 9/metabolismo
11.
Theranostics ; 14(7): 2934-2945, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38773971

RESUMEN

Rationale: Nucleic acid constructs are commonly used for vaccination, immune stimulation, and gene therapy, but their use in cancer still remains limited. One of the reasons is that systemic delivery to tumor-associated antigen-presenting cells (dendritic cells and macrophages) is often inefficient, while off-target nucleic acid-sensing immune pathways can stimulate systemic immune responses. Conversely, certain carbohydrate nanoparticles with small molecule payloads have been shown to target these cells efficiently in the tumor microenvironment. Yet, nucleic acid incorporation into such carbohydrate-based nanoparticles has proven challenging. Methods: We developed a novel approach using cross-linked bis succinyl-cyclodextrin (b-s-CD) nanoparticles to efficiently deliver nucleic acids and small-molecule immune enhancer to phagocytic cells in tumor environments and lymph nodes. Our study involved incorporating these components into the nanoparticles and assessing their efficacy in activating antigen-presenting cells. Results: The multi-modality immune stimulators effectively activated antigen-presenting cells and promoted anti-tumor immunity in vivo. This was evidenced by enhanced delivery to phagocytic cells and subsequent immune response activation in tumor environments and lymph nodes. Conclusion: Here, we describe a new approach to incorporating both nucleic acids and small-molecule immune enhancers into cross-linked bis succinyl-cyclodextrin (b-s-CD) nanoparticles for efficient delivery to phagocytic cells in tumor environments and lymph nodes in vivo. These multi-modality immune stimulators can activate antigen-presenting cells and foster anti-tumor immunity. We argue that this strategy can potentially be used to enhance anti-tumor efficacy.


Asunto(s)
Células Dendríticas , Nanopartículas , Ácidos Nucleicos , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Animales , Ácidos Nucleicos/administración & dosificación , Ratones , Nanopartículas/química , Ciclodextrinas/química , Ratones Endogámicos C57BL , Humanos , Línea Celular Tumoral , Tropismo , Microambiente Tumoral/efectos de los fármacos , Ganglios Linfáticos/inmunología , Femenino , Neoplasias/terapia , Neoplasias/inmunología
12.
Angew Chem Int Ed Engl ; 63(24): e202318870, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38578432

RESUMEN

Multiplexed bead assays for solution-phase biosensing often encounter cross-over reactions during signal amplification steps, leading to unwanted false positive and high background signals. Current solutions involve complex custom-designed and costly equipment, limiting their application in simple laboratory setup. In this study, we introduce a straightforward protocol to adapt a multiplexed single-bead assay to standard fluorescence imaging plates, enabling the simultaneous analysis of thousands of reactions per plate. This approach focuses on the design and synthesis of bright fluorescent and magnetic microspheres (MagSiGlow) with multiple fluorescent wavelengths serving as unique detection markers. The imaging-based, single-bead assay, combined with a scripted algorithm, allows the detection, segmentation, and co-localization on average of 7500 microspheres per field of view across five imaging channels in less than one second. We demonstrate the effectiveness of this method with remarkable sensitivity at low protein detection limits (100 pg/mL). This technique showed over 85 % reduction in signal cross-over to the solution-based method after the concurrent detection of tumor-associated protein biomarkers. This approach holds the promise of substantially enhancing high throughput biosensing for multiple targets, seamlessly integrating with rapid image analysis algorithms.


Asunto(s)
Colorantes Fluorescentes , Microesferas , Dióxido de Silicio , Dióxido de Silicio/química , Colorantes Fluorescentes/química , Humanos , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/metabolismo , Técnicas Biosensibles/métodos
13.
Sci Rep ; 14(1): 9285, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654081

RESUMEN

Aerosols (PM 2.5 and PM 10 ) represent one of the most critical pollutants due to their negative effects on human health. This research analyzed the relationship of PM and its PM 2.5 /PM 10 ratios with climatic variables in the austral spring (2016-2018) in Metropolitan Lima. Overall, there was an average PM 2.5 /PM 10 ratio of 0.33 with fluctuations from 0.30 to 0.35. However, there have also been high point values that reached ratios greater than one. This situation indicates a moderate condition of contamination by particulate matter with a predominance of coarse aerosols in spring, with an increasing trend over the years. The locations Ate and Villa Maria del Triunfo, especially Ate, presented poor quality conditions. Thursdays showed outstanding pollution peaks by PM 10 , and a decrease is visible on Sundays. On the other hand, the PM 2.5 showed a similar pattern every day, including Sundays. The maximum peaks occurred in the morning and night hours. The increase in anthropogenic emissions associated with the formation of secondary aerosols has been evident, being the case of the location Campo de Marte, the one that had a significant increase in ratios PM 2.5 /PM 10 , which confirms a greater intensity of secondary formations of carbonaceous particles from industrial oil sources, vehicle exhaust, as well as aerosols from metal smelting and biomass burning. There were negative correlations of the ratios with PM 10 , temperature, wind speed, and direction, and positive correlations with PM 2.5 and relative humidity. Contour lines were successfully developed that demonstrated the interaction of climate with PM 2.5 /PM 10 ratios. This will deepen the exploration of emission sources and modeling, which allows for optimizing air quality indices to control emissions and adequately manage air quality in Metropolitan Lima.

14.
Vaccines (Basel) ; 12(4)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38675788

RESUMEN

Vaccines are indispensable tools in the battle against infectious diseases and hold great potential in combating a myriad of other diseases [...].

15.
Crit Rev Microbiol ; : 1-21, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38634723

RESUMEN

Epstein-Barr Virus (EBV), a dsDNA herpesvirus, is believed to play a significant role in exacerbating and potentially triggering autoimmune and autoinflammatory maladies. Around 90% of the world is infected with the virus, which establishes latency within lymphocytes. EBV is also known to cause infectious mononucleosis, a self-limited flu-like illness, in adolescents. EBV is often reactivated and it employs several mechanisms of evading the host immune system. It has also been implicated in inducing host immune dysfunction potentially resulting in exacerbation or triggering of inflammatory processes. EBV has therefore been linked to a number of autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and Sjögren's syndrome. The review examines the molecular mechanisms through which the virus alters host immune system components thus possibly resulting in autoimmune processes. Understanding the mechanisms underpinning EBV-associated autoimmunity is pivotal; however, the precise causal pathways remain elusive. Research on therapeutic agents and vaccines for EBV has been stagnant for a long number of years until recent advances shed light on potential therapeutic targets. The implications of EBV in autoimmunity underscore the importance of developing targeted therapeutic strategies and, potentially, vaccines to mitigate the autoimmune burden associated with this ubiquitous virus.

16.
Front Mol Biosci ; 11: 1243366, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38638687

RESUMEN

Introduction: The Epstein-Barr virus has been associated with a considerable number of autoimmune diseases. We have previously demonstrated that EBV DNA enhances the production of IL-17A, a pro-inflammatory cytokine, via endosomal Toll-like receptor signalling. Methods: We used RNA-seq to analyze the transcriptional profile of mouse immune cells treated with EBV DNA. Results: We observed that EBV DNA upregulates an IL-17A-centric network of mediators. Ensemble Gene Set Enrichment Analysis (EGSEA) showed enriched expression of sets involved in inflammatory responses including IFNγ and TNF-α-associated pathways as well as proinflammatory diseases. On the other hand, while macrophages and B cells were somewhat able to induce an IL-17A response from T cells to EBV DNA, they were less potent than dendritic cells. EBV virions were also capable of eliciting the production of inflammatory mediators from dendritic cell-T cell cultures largely mirroring responses to the viral DNA. Conclusions: Given the wide prevalence of EBV in the population, our analyses reveal a network of mediators and cell types that may serve as therapeutic targets in a large proportion of people affected by autoimmune diseases.

17.
Viruses ; 16(4)2024 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-38675965

RESUMEN

Epstein-Barr virus (EBV), a Herpesviridae family member, is associated with an increased risk of autoimmune disease development in the host. We previously demonstrated that EBV DNA elevates levels of the pro-inflammatory cytokine IL-17A and that inhibiting Toll-like receptor (TLR) 3, 7, or 9 reduces its levels. Moreover, this DNA exacerbated colitis in a mouse model of inflammatory bowel disease (IBD). In the study at hand, we examined whether inhibition of TLR3, 7, or 9 alleviates this exacerbation. Mice were fed 1.5% dextran sulfate sodium (DSS) water and administered EBV DNA. Then, they were treated with a TLR3, 7, or 9 inhibitor or left untreated. We also assessed the additive impact of combined inhibition of all three receptors. Mice that received DSS, EBV DNA, and each inhibitor alone, or a combination of inhibitors, showed significant improvement. They also had a decrease in the numbers of the pathogenic colonic IL-17A+IFN-γ+ foci. Inhibition of all three endosomal TLR receptors offered no additive benefit over administering a single inhibitor. Therefore, inhibition of endosomal TLRs reduces EBV DNA exacerbation of mouse colitis, offering a potential approach for managing IBD patients infected with EBV.


Asunto(s)
ADN Viral , Herpesvirus Humano 4 , Enfermedades Inflamatorias del Intestino , Receptores Toll-Like , Animales , Femenino , Ratones , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/virología , Sulfato de Dextran , Modelos Animales de Enfermedad , ADN Viral/efectos adversos , ADN Viral/farmacología , Endosomas/efectos de los fármacos , Endosomas/metabolismo , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inducido químicamente , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/virología , Interleucina-17/metabolismo , Ratones Endogámicos C57BL , Receptor Toll-Like 3/antagonistas & inhibidores , Receptor Toll-Like 3/metabolismo , Receptor Toll-Like 7/antagonistas & inhibidores , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 9/antagonistas & inhibidores , Receptor Toll-Like 9/metabolismo , Receptores Toll-Like/antagonistas & inhibidores , Receptores Toll-Like/metabolismo
18.
Psychiatry Res Neuroimaging ; 340: 111805, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38447230

RESUMEN

Altered brain network profiles in schizophrenia (SCZ) during memory consolidation are typically observed during task-active periods such as encoding or retrieval. However active processes are also sub served by covert periods of memory consolidation. These periods are active in that they allow memories to be recapitulated even in the absence of overt sensorimotor processing. It is plausible that regions central to memory formation like the dlPFC and the hippocampus, exert network signatures during covert periods. Are these signatures altered in patients? The question is clinically relevant because real world learning and memory is facilitated by covert processing, and may be impaired in schizophrenia. Here, we compared network signatures of the dlPFC and the hippocampus during covert periods of a learning and memory task. Because behavioral proficiency increased non-linearly, functional connectivity of the dlPFC and hippocampus [psychophysiological interaction (PPI)] was estimated for each of the Early (linear increases in performance) and Late (asymptotic performance) covert periods. During Early periods, we observed hypo-modulation by the hippocampus but hyper-modulation by dlPFC. Conversely, during Late periods, we observed hypo-modulation by both the dlPFC and the hippocampus. We stitch these results into a conceptual model of network deficits during covert periods of memory consolidation.


Asunto(s)
Consolidación de la Memoria , Esquizofrenia , Humanos , Corteza Prefontal Dorsolateral , Corteza Prefrontal , Esquizofrenia/diagnóstico por imagen , Mapeo Encefálico , Imagen por Resonancia Magnética , Hipocampo
19.
Adv Sci (Weinh) ; 11(15): e2309026, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38342608

RESUMEN

Tumor-associated macrophages (TAM) are a diverse population of myeloid cells that are often abundant and immunosuppressive in human cancers. CXCL9Hi TAM has recently been described to have an antitumor phenotype and is linked to immune checkpoint response. Despite the emerging understanding of the unique antitumor TAM phenotype, there is a lack of TAM-specific therapeutics to exploit this new biological understanding. Here, the discovery and characterization of multiple small-molecule enhancers of chemokine ligand 9 (CXCL9) and their targeted delivery in a TAM-avid systemic nanoformulation is reported. With this strategy, it is efficient encapsulation and release of multiple drug loads that can efficiently induce CXCL9 expression in macrophages, both in vitro and in vivo in a mouse tumor model. These observations provide a window into the molecular features that define TAM-specific states, an insight a novel therapeutic anticancer approach is used to discover.


Asunto(s)
Neoplasias , Macrófagos Asociados a Tumores , Animales , Humanos , Ratones , Quimiocina CXCL9/genética , Quimiocina CXCL9/metabolismo , Macrófagos/metabolismo , Neoplasias/patología , Fenotipo
20.
Vaccines (Basel) ; 12(1)2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38276676

RESUMEN

Vaccination provides the best protection against the increasing infections of SARS-CoV-2. The magnitude and type of anti-SARS-CoV-2 vaccine side effects (SEs) depend on parameters that are not fully understood. In this cross-sectional study, the associations between different anti-SARS-CoV-2 vaccine SEs and age, sex, the presence of chronic diseases, medication intake, history of allergies, and infections with SARS-CoV-2 were investigated. Our survey used the Google platform and had 866 participants, contacted through e-mails, social media and chain referral sampling (margin of error ≈ 4.38%, 99% confidence). More than 99% of the participants received the BNT162b2 and ChAdOx1-S vaccines. Being female, having chronic diseases, taking medicines routinely and the presence of a SARS-CoV-2 infection (p < 0.05) were associated with strong SEs after the BNT162b2 vaccine second dose. Having a history of allergies and a female sex (p < 0.01) were associated with strong SEs after the ChAdOx1-S vaccine second dose. Furthermore, the results reveal, for the first time, the associations between having a history of allergies, chronic diseases, medication usage, and SEs of a strong magnitude for the BNT162b2 and ChAdOx1-S vaccines. Additionally, this study supports the association of the female sex and infection with SARS-CoV-2 with an increased potential of developing stronger SEs with certain anti-SARS-CoV-2 vaccines.

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