CD155/PVR determines acute myeloid leukemia targeting by Delta One T cells.

ABSTRACT: Relapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed a Vδ1+ γδ T cell-based product for adoptive immunotherapy, named Delta One T (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines and primary blasts in vitro and in vivo. However, the molecular mechanisms responsible for the broad DOT-cell recognition of AML cells remain poorly understood. Here, we dissected the role of natural killer (NK) cell receptor ligands in AML cell recognition by DOT cells. Screening of multiple AML cell lines highlighted a strong upregulation of the DNAM-1 ligands, CD155/pulmonary vascular resistance (PVR), CD112/nectin-2, as well as the NKp30 ligand, B7-H6, in contrast with NKG2D ligands. CRISPR-mediated ablation revealed key nonredundant and synergistic contributions of PVR and B7-H6 but not nectin-2 to DOT-cell targeting of AML cells. We further demonstrate that PVR and B7-H6 are critical for the formation of robust immunological synapses between AML and DOT cells. Importantly, PVR but not B7-H6 expression in primary AML samples predicted their elimination by DOT cells. These data provide new mechanistic insight into tumor targeting by DOT cells and suggest that assessing PVR expression levels may be highly relevant to DOT cell-based clinical trials.

In-depth analysis of the interplay between oncogenic mutations and NK cell-mediated cancer surveillance in solid tumors.

Natural killer (NK) cells play a crucial role in antitumoral and antiviral responses. Yet, cancer cells can alter themselves or the microenvironment through the secretion of cytokines or other factors, hindering NK cell activation and promoting a less cytotoxic phenotype. These resistance mechanisms, often referred to as the "hallmarks of cancer" are significantly influenced by the activation of oncogenes, impacting most, if not all, of the described hallmarks. Along with oncogenes, other types of genes, the tumor suppressor genes are frequently mutated or modified during cancer. Traditionally, these genes have been associated with uncontrollable tumor growth and apoptosis resistance. Recent evidence suggests oncogenic mutations extend beyond modulating cell death/proliferation programs, influencing cancer immunosurveillance. While T cells have been more studied, the results obtained highlight NK cells as emerging key protagonists for enhancing tumor cell elimination by modulating oncogenic activity. A few recent studies highlight the crucial role of oncogenic mutations in NK cell-mediated cancer recognition, impacting angiogenesis, stress ligands, and signaling balance within the tumor microenvironment. This review will critically examine recent discoveries correlating oncogenic mutations to NK cell-mediated cancer immunosurveillance, a relatively underexplored area, particularly in the era dominated by immune checkpoint inhibitors and CAR-T cells. Building on these insights, we will explore opportunities to improve NK cell-based immunotherapies, which are increasingly recognized as promising alternatives for treating low-antigenic tumors, offering significant advantages in terms of safety and manufacturing suitability.

[Pilot programme for screening perimenopausal women for cardiovascular risk from community pharmacy: MENOVASC Project]. / Programa piloto de cribado de riesgo cardiovascular en la mujer perimenopáusica desde la farmacia comunitaria: proyecto 'MENOVASC'.

Introduction: Cardiovascular diseases have been the leading cause of death in the world for more than 20 years. They are generally unusual in premenopausal women due to the cardiovascular protection of endogenous estrogens, so the cardiovascular risk in these has traditionally been underestimated. Objectives: Establish a protocol for vascular risk screening in perimenopausal women from the community pharmacy. Material and methods: Descriptive study from an opportunistic sample in a community pharmacy of women between 45 and 55 years old. Participants were cited at the pharmacy and their cholesterol and blood pressure levels, weight, and height were taken. Information was collected on women's general and specific cardiovascular risk factors, medication they were taking and smoking. These data were used to estimate cardiovascular risk using SCORE tables. Results: 18 forms were collected, with the average age of the applicants being 49 (SD 3) years old. 38.9% (CI95%: 17.3 a 64.3) had high blood pressure and 44.4% (CI95%: 21.5 a 69.2) had cholesterol levels equal to or higher than 190 mg/ml. 100% had some traditional or specific risk factor for women. Conclusions: The usefulness of vascular risk screening in perimenopausal women is confirmed. All this places value on the intervention of the community pharmacist in the detection and management of cardiovascular risk factors.

Nefrolitiasis en la paciente gestante: revisión de la literatura / Renal lithiasis in pregnant patient: a literary review

Resumen La litiasis renal en la paciente gestante es una condición relativamente infrecuente; sin embargo, es la causa más común de dolor no obstétrico durante el embarazo. En el periodo de gestación se producen diversos cambios anatomofisiológicos en el tracto urinario, como la dilatación de los cálices renales, la pelvis renal y los uréteres por causa del efecto que ejerce la progesterona sobre el músculo liso uretral, y la compresión de los uréteres por el útero grávido. Estas modificaciones conducen a un aumento del flujo plasmático renal y de la tasa de filtrado glomerular, ocasionando hiperuricosuria e hipercalciuria. Del mismo modo, durante el embarazo también se produce un aumento de la secreción de inhibidores de cálculos, por lo cual la prevalencia de la formación de cálculos durante el embarazo es similar a la de las mujeres no embarazadas. El bajo índice de sospecha por parte del médico tratante puede entorpecer el diagnóstico y el tratamiento de esta patología, que también son limitados en la gestación debido a los potenciales riesgos teratogénicos. Se realiza una revisión narrativa de la literatura partiendo de la evidencia científica disponible en las diferentes bases de datos y de esta manera se pretende instruir al médico en los aspectos clave de dicho tema.

Abstract Renal lithiasis in pregnant women is a relatively rare condition. However, it is the most common cause of non-obstetric pain during pregnancy. During the gestation period, various anatomical-physiological changes occur in the urinary tract. These changes include dilation of the renal calyces, renal pelvis, and ureters due to the effect of progesterone on urethral smooth muscle and compression of the ureters by the gravid uterus. These modifications lead to an increase in renal plasma flow and glomerular filtration rate, thus causing hyperuricosuria and hypercalciuria. Similarly, during pregnancy there is also an increase in the secretion of stone inhibitors, therefore, the prevalence of stone formation during pregnancy is similar to non-pregnant women. The low index of suspicion on the part of the treating physician can hinder the diagnosis and treatment of this pathology, which is also limited in pregnancy due to teratogenic risks. A narrative review of the literature is carried out based on the scientific evidence available in the different databases and in this way it is intended to instruct the doctor in the key aspects of said topic.

Amiloidosis asociada a hemodiálisis: revisión de sus aspectos etiopatogénicos / Hemodialysis-Associated Amyloidosis: Review of its ethiopathogenic aspects

Resumen La amiloidosis constituye una complicación importante en los pacientes con enfermedad renal crónica que son sometidos a hemodiálisis durante extensos períodos de tiempo. Al igual que en otras amiloidosis sistémicas, en la amiloidosis asociada a hemodiálisis intervienen diferentes sustancias, algunas de ellas de carácter fibrilar, como la βeta-2-microglobulina, la cual representa una de las proteínas de mayor relevancia dada su implicación etiopatogénica. A pesar de que las técnicas de hemodiálisis han sido mejoradas con el paso de los años, dicha entidad continúa siendo una complicación relativamente frecuente; tal es que se puede presentar hasta en el 80 % de los pacientes con hemodiálisis prolongadas. Por lo tanto, se hizo imprescindible realizar una revisión narrativa partiendo de la literatura científica disponible en las diferentes bases de datos, con el objetivo de contribuir a mejorar y actualizar el conocimiento del médico en dicho tópico; al abarcar desde los aspectos generales y su fisiopatología, hasta su presentación clínica, diagnóstico y tratamiento.

Abstract Amyloidosis is a major complication in patients with chronic kidney disease who undergo hemodialysis for long periods of time. As in other systemic amyloidosis, different substances are involved in amyloidosis associated with different substances, some of them fibrillar in nature, such as βeta-2-microglobulin, which represents one of the most relevant proteins given its etiopathogenic involvement. Despite the fact that hemodialysis techniques have been improved over the years, this entity continues to be a frequent complication; such is that it can occur in up to 80% of patients with prolonged hemodialysis. Therefore, it was essential to carry out a narrative review based on the scientific literature available in the different databases with the aim of contributing to improve and update the doctor's knowledge on this topic; ranging from the general aspects and its pathophysiology, to its clinical presentation, diagnosis, and treatment.

Edulcorantes artificiales y su papel en la enfermedad renal crónica: una revisión

Los edulcorantes no calóricos surgieron como una opción segura y saludable en el marco de la alimentación y, por lo tanto, han sido de gran interés en la cultura dietética adquirida en la actualidad; es importante mencionar que en esta cultura adquirida el consumo de comida rápida y con altos niveles de azúcar ha tomado especial fuerza, lo que repercute negativamente en la incidencia de enfermedades metabólicas. En este orden de ideas, los edulcorantes no calóricos se convierten en una mejor opción para la salud en la que no es necesario hacer un cambio drástico en el estilo de vida. No obstante, los beneficios de los edulcorantes artificiales no calóricos no han sido estudiados a profundidad y no se ha evidenciado que una dieta a base de estos sustitutivos provoque un cambio significativo en el desarrollo de enfermedades metabólicas asociadas al consumo de azúcar, por el contrario, se han relacionado con enfermedades como obesidad, diabetes mellitus tipo 2 y síndrome metabólico. Asimismo, estos pueden provocar una serie de cambios metabólicos a través de distintos mecanismos que terminan en proteinuria progresiva y descenso de la tasa de filtrado glomerular. A partir de lo anterior, se hace necesario un análisis del riesgo que se corre al elegir esta opción alimenticia, para así no dejarse llevar por los procesos mediáticos que los promocionan, sino más bien, regirse por los hallazgos científicos.

Non-caloric artificial sweeteners have emerged to offer a safe and healthy option in the framework of food. They have received special attention in recent decades, precisely because of the current food culture, where fast food and high sugar consumption have taken on special strength, which has a negative impact on the incidence of metabolic diseases. In that order of ideas, non-caloric artificial sweeteners propose better health without the need for a drastic change in lifestyle. However, its benefits have not been studied in depth, in addition to the fact that there has been no significant change in the development of metabolic diseases associated with sugar consumption, on the contrary, they have been related to diseases such as obesity, type 2 diabetes mellitus and metabolic syndrome. Likewise, they cause a series of metabolic changes by different mechanisms that end in progressive proteinuria and a decrease in the glomerular filtration rate. In order with the above, an analysis of the risk to which one is subjected when choosing this food option is necessary, and not be deafened, much less dazzled by the media processes, if not rather, be governed by scientific findings.