The Dynamics of Histone Modifications during Mammalian Zygotic Genome Activation.

Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a maternal-to-zygotic transition (MZT) and subsequent zygotic genome activation (ZGA), marking the initiation of transcriptional control and gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity and gene expression in many mammals. Recent advances in chromatin analysis have enabled detailed explorations of histone modifications during ZGA. This review delves into conserved and unique regulatory strategies, providing essential insights into the dynamic changes in histone modifications and their variants during ZGA in mammals. The objective is to explore recent advancements in leading mechanisms related to histone modifications governing this embryonic development phase in depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation in diverse biological contexts. It will also contribute to the extensive areas of evolutionary and developmental biology and possibly lay the foundation for future research and discussion on this seminal topic.

Molecular study of a large cohort of 109 haemophilia patients from Cuba using a gene panel with next generation sequencing-based technology.

INTRODUCTION: In several countries, molecular diagnosis of haemophilia A (HA) and B (HB) is hampered by a lack of resources for DNA analysis. The advent of next-generation sequencing (NGS) has enabled gene analysis at a reasonable cost. AIM: Describe a collaboration between Cuban and Spanish researchers to identify candidate variants and investigate the molecular epidemiology of 106 Cuban haemophilia patients using NGS. PATIENTS/METHODS: The molecular analysis protocol included well-established LR-PCR procedures to detect F8 inversions, NGS with a 30-gene panel to sequence F8 and F9, and multiplex ligation-dependent probe amplification to identify large structural variants. RESULTS: One-hundred and thirty-one candidate variants were identified along F8, F9, and VWF; 72 were unique and 28 (39%) had not been previously recorded. Putative variants were identified in 105/106 patients. Molecular characterization enabled confirmation and reclassification of: 90 HA (85%), 15 HB (14%), and one type 2N VWD (1%). Null variants leading to non-production of FVIII or FIX were common in severe HA (64%), moderate HA (74%), and severe HB (60%), whereas missense variants were frequent in mild HA (57%) and moderate or mild HB (83%). Additional variants in VWF were identified in 16 patients. CONCLUSION: This is the first description of the molecular epidemiology of HA and HB in Cuba. Variants identified in index cases will be of value for local implementation of familial studies and prenatal diagnosis using the molecular approaches available in Cuba. The results of this protocolled genetic study improved the accuracy of the clinical diagnosis and will facilitate management of these patients.

Refractory pemphigus vulgaris and high-intensity extracorporeal photopheresis: A case report.

A 41-year-old man with oral pemphigus vulgaris (PV) presented to our clinic with a history of no response to numerous immunosuppressant agents and was referred for extracorporeal photopheresis (ECP) therapy. Although the patient underwent a high-intensity ECP regimen for five months, which included two different photopheresis systems, his oral dysesthesia continued to interfere with oral intake, leading to continued weight loss and other adverse events. The intervention was associated with changes in several immune cell subpopulations without modifying the anti-epidermal antibody titers, aligned with his poor clinical outcome. To the best of the authors' knowledge, this is the first report to examine immunophenotyping of a PV patient who was refractory to previous immunosuppression and recalcitrant to high-intensity ECP therapy.

Wide Range Applications of Spirulina: From Earth to Space Missions.

Spirulina is the most studied cyanobacterium species for both pharmacological applications and the food industry. The aim of the present review is to summarize the potential benefits of the use of Spirulina for improving healthcare both in space and on Earth. Regarding the first field of application, Spirulina could represent a new technology for the sustainment of long-duration manned missions to planets beyond the Lower Earth Orbit (e.g., Mars); furthermore, it could help astronauts stay healthy while exposed to a variety of stress factors that can have negative consequences even after years. As far as the second field of application, Spirulina could have an active role in various aspects of medicine, such as metabolism, oncology, ophthalmology, central and peripheral nervous systems, and nephrology. The recent findings of the capacity of Spirulina to improve stem cells mobility and to increase immune response have opened new intriguing scenarios in oncological and infectious diseases, respectively.

Aging: Disease or "natural" process? A glimpse from regenerative medicine.

We explore aging as a global phenomenon, questioning whether it constitutes a treatable condition or follows a natural course. Acknowledging its multifactorial nature, we delve into the challenges and opportunities inherent in this intricate biological process. The inclusion of old age in the 11th International Classification of Diseases sparks debate, categorizing it as a disease based on mechanistic explanations, blood-based biomarkers, and anti-aging products. Ethical dilemmas arise, emphasizing the difficulty of defining the transition from normal to pathological states during this process. We suggest that aging should be regarded as a treatable condition without necessarily labeling it a 'disease.' While anti-aging research unveils promising interventions like Metformin, Rapamycin, and cellular therapy, achieving biological immortality remains a formidable challenge. The future promises to prolong life and enhance quality by comprehensively understanding aging's implications for human health.

Application of mass cytometry to characterize hematopoietic stem cells in apheresis products of patients with hematological malignancies.

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is a widely used therapy, but its success largely depends on the number and quality of stem cells collected. Current evidence shows the complexity of the hematopoietic system, which implies that, in the quality assurance of the apheresis product, the hematopoietic stem cells are adequately characterized and quantified, in which mass cytometry (MC) can provide its advantages in high-dimensional analysis. OBJECTIVE: This research aimed to characterize and enumerate CD45dim/CD34+ stem cells using the MC in apheresis product yields from patients with chronic lymphoid malignant diseases undergoing autologous transplantation at the Abu Dhabi Stem Cells Center. METHODS: An analytical and cross-sectional study was performed on 31 apheresis products from 15 patients diagnosed with multiple myeloma (n = 9) and non-Hodgkin lymphomas (n = 6) eligible for HSCT. The MC was employed using the MaxPar Kit for stem cell immunophenotyping. The analysis was performed manually in the Kaluza and unsupervised by machine learning in Cytobank Premium. RESULTS: An excellent agreement was found between mass and flow cytometry for the relative and absolute counts of CD45dim/CD34+ cells (Bland-Altman bias: -0.029 and -64, respectively), seven subpopulations were phenotyped and no lineage bias was detected for any of the methods used in the pool of collected cells. A CD34+/CD38+/CD138+ population was seen in the analyses performed on four patients with multiple myeloma. CONCLUSIONS: The MC helps to characterize subpopulations of stem cells in apheresis products. It also allows cell quantification by double platform. Unsupervised analysis allows results completion and validation of the manual strategy. The proposed methodology can be extended to apheresis products for purposes other than HSCT.

Safety and efficacy of autologous non-hematopoietic enriched stem cell nebulization in COVID-19 patients: a randomized clinical trial, Abu Dhabi 2020.

BACKGROUND: The novel SARS-CoV-2 has caused the coronavirus disease 2019 (COVID-19) pandemic. Currently, with insufficient worldwide vaccination rates, identifying treatment solutions to reduce the impact of the virus is urgently needed. METHOD: An adaptive, multicentric, open-label, and randomized controlled phase I/II clinical trial entitled the "SENTAD-COVID Study" was conducted by the Abu Dhabi Stem Cells Center under exceptional conditional approval by the Emirates Institutional Review Board (IRB) for COVID-19 Research Committee from April 4th to July 31st, 2020, using an autologous peripheral blood non-hematopoietic enriched stem cell cocktail (PB-NHESC-C) administered by compressor (jet) nebulization as a complement to standard care therapy. The primary endpoints include safety and efficacy assessments, adverse events, the mortality rate within 28 days, and the time to clinical improvement as measured by a 2-point reduction on a seven-category ordinal scale or discharge from the hospital whichever occurred first. RESULTS: The study included a total of 139 randomized COVID-19 patients, with 69 in the experimental group and 70 in the control group (standard care). Overall survival was 94.20% for the cocktail-treated group vs. 90.27% for the control group. Adverse events were reported in 50 (72.46%) patients receiving PB-NHESC-C and 51 (72.85%) in the control group (p = 0.9590), with signs and symptoms commonly found in COVID-19. After the first 9 days of the intervention, 67.3% of cocktail-treated patients recovered and were released from hospitals compared to 53.1% (RR = 0.84; 95% CI, 0.56-1.28) in the control group. Improvement, i.e., at least a 2-point reduction in the severity scale, was more frequently observed in cocktail-treated patients (42.0%) than in controls (17.0%) (RR = 0.69; 95% CI, 0.56-0.88). CONCLUSIONS: Cocktail treatment improved clinical outcomes without increasing adverse events. Thus, the nebulization of PB-NHESC-C was safe and effective for treatment in most of these patients. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04473170. It was retrospectively registered on July 16th, 2020.

Viability assessment of human peripheral blood-derived stem cells after three methods of nebulization.

BACKGROUND AND OBJECTIVES: Drug delivery by nebulization has become a crucial strategy for treating different respiratory and lung diseases. Emerging evidence implicates stem cell therapy as a promising tool in treating such conditions, not only by alleviating the related symptoms but by improving the prognosis. However, delivery of human peripheral blood-derived stem cells (hPBSCs) to the respiratory airways remains an innovative approach yet to be realized. This study is an analytic, translational, and in vitro research to assess the viability and morphological changes of identified cell populations in hPBSCs cocktail derived from COVID-19 patients. METHODS AND RESULTS: Peripheral blood (PB) samples were obtained from patients enrolled in the SENTAD-COVID Study (ClinicalTrials.gov Reference: NCT04473170). hPBSCs cocktails (n=15) were provided by the Cells Processing Laboratory of Abu Dhabi Stem Cells Center, and were nebulized by three different methods of nebulization: compressor (jet), ultrasonic, and mesh. Our results reported that nucleated CD45dim cell count was significantly lower after the three nebulization methods, but nucleated CD45- cells show a significant decrease only after mesh nebulization. Mesh-nebulized samples had a significant reduction in viability of both CD45dim and CD45- cells. CONCLUSIONS: This study provides evidence that stem cells derived from PB of COVID-19 patients can be nebulized without substantial loss of cell viability, cell count, and morphological changes using the compressor nebulization. Therefore, we recommend compressor nebulizers as the preferable procedure for hPBSCs delivery to the respiratory airways in further clinical settings.

Las donaciones de sangre en Cuba desde una perspectiva histórica / Blood donations in Cuba from a historical perspective

Introducción: Las donaciones de sangre constituyen una actividad sanitaria de importancia estratégica, su historia ha evolucionado junto a la del sistema de salud cubano. Objetivo: Describir el comportamiento de las donaciones de sangre desde una perspectiva histórica, según las etapas del desarrollo del sistema sanitario cubano. Métodos: Se realizó una investigación por el método histórico-lógico sobre los antecedentes históricos y la actualidad de las donaciones de sangre. La información se obtuvo mediante la entrevista y las revisiones bibliográfica y documental. Resultados: Durante la seudorepública se fundaron las primeras instituciones de salud para las donaciones y transfusiones de sangre, su administración se fundamentaba en las recolecciones provenientes de los donantes remunerados y familiares. En el período revolucionario se logró un programa de sangre organizado e integrado al sistema de salud, por primera vez unificado y de alcance nacional, con la participación coordinada entre el personal del nivel primario de atención y las organizaciones sociales. Esto permitió el creciente y considerable incremento de la disponibilidad de sangre y el desarrollo de la medicina transfusional, las especialidades médico-quirúrgicas y la industria médico-farmacéutica cubanas. Además, se consolidó la práctica de donar sangre como un acto voluntario. Conclusiones: La donación de sangre en Cuba constituye una actividad trazadora que muestra el desarrollo del sistema sanitario cubano en sus diferentes etapas y es reflejo de la voluntad política del gobierno, el pueblo y sus instituciones(AU)

Introduction: Blood donations are health care activity of a strategic importance. Their history has evolved together with the Cuban health system. Objective: To describe the behaviour of blood donations from a historical perspective according to the development stages of the Cuban health system. Method: It was carried out a research by the logic-historical method on the historical background and the current data on blood donations. The information was collected through interviews and the bibliographic and documentary reviews. Results: During the pseudo-republic times, the first institutions for blood donations and transfusions were created, and their managements was supported with the collections of paid donors and relatives. In the Revolution period, it was achieved an organized blood donation program which was integrated to the health system and for the fist time unified and of national scope, with coordinated participation between the staff of the first level of care and the social organizations. This allowed the significant increase of the availability of blood and the development of the Cuban transfusion medicine, medical-surgical specialties and medical-pharmaceutical industry. In addition, it was strengthen the practice of blood donation as a voluntary act. Conclusions: Blood donation in Cuba is a trace activity that shows the development of the Cuban health system in its different stages and it is a reflection of the political will of the Government, the people and the institutions(AU)

Exosomas: terapia celular regenerativa libre de células / Exosomes: "cell-free" regenerative cell therapy

La terapia celular basada en células mesenquimales/estromales se aplica ampliamente en la medicina moderna, aun cuando no todos los mecanismos de supervivencia y diferenciación están identificados. Sin embargo, hace pocos años se comenzaron a encontrar elementos extracelulares que generan nuevos paradigmas. En el presente trabajo se explican las principales características y funciones atribuidas a los exosomas, nanopartículas constituidas por microvesículas secretadas por las células con efecto en la matriz extracelular, y su repercusión como alternativa hacia una medicina regenerativa libre de células. Estas estructuras participan de forma notoria y crucial en la comunicación intercelular, lo que ha supuesto un cambio en el concepto de las funciones y el papel que desempeñan estas vesículas en los organismos vivos, en particular en la restauración de tejidos dañados y la respuesta inflamatoria e inmunológica. Se comentan algunos ejemplos de la repercusión biotecnológica de los exosomas en empresas y el mercado biofarmaceútico(AU)

Mesenchymal/stromal cell ;based therapy is widely applied in modern medicine, even though not all survival and differentiation mechanisms are identified. However, a few years ago, extracellular elements began to be found that generate new paradigms. The present work explains the main characteristics and functions attributed to exosomes, nanoparticles made up of microvesicles secreted by with an effect on the extracellular matrix, and their impact as an alternative towards cell-free regenerative medicine. These structures participate, notoriously and critically, in intercellular communication, which has led to a change in the concept of the functions and role that these vesicles play within living organisms, particularly in the restoration of damaged tissues and the inflammatory and immunological response. Some examples of the exosomes' biotechnological impact on companies and the biopharmaceutical market are discussed(AU)

Razones para un banco de sangre de cordón umbilical en el Instituto de Hematología e Inmunología de Cuba / Reasons for a cord blood bank at the Institute of Hematology and Immunology, Cuba

Durante los últimos 45 años, el trasplante alogénico de células progenitoras hematopoyéticas ha sido una modalidad de tratamiento cada vez más utilizada en la curación de hemopatías malignas y otras enfermedades genéticas como la drepanocitosis y algunas inmunodeficiencias primarias. Sin embargo, la falta de donantes adecuados, por carecer los pacientes de hermanos que puedan ser histocompatibles, ha hecho necesaria la búsqueda de alternativas en donantes no relacionados para garantizar la eficacia y seguridad del trasplante. Una fuente muy utilizada es la sangre de cordón umbilical (SCU); el primer trasplante con SCU se realizó en 1989 y en los últimos 25 años este tipo de trasplante se ha aplicado ampliamente en los países desarrollados. Los bancos de SCU se han convertido en una reserva de importancia para estos tratamientos y para la terapia celular regenerativa, por sus múltiples ventajas. Contar con un banco público de SCU en Cuba es una necesidad para el desarrollo del Sistema Nacional de Salud que permitiría unir nuestros esfuerzos a la comunidad científica internacional en la lucha por una salud pública mejor para nuestro pueblo y otros pueblos del mundo, en particular para la América Latina

During the last 45 years, alogenic stem cell transplant has been an every day most used form of treatment for the cure of malignant hemopathies and other genetic disorders such as sickle cell disease and some primary immunodeficiencies. Nevertheless, the lack of adequate donors caused by not having the patients possible histocompatible relatives has made it necessary to look for alternatives in non relateddonors to guarantee the efficacy and security of the transplant. A commonly used source is cord blood (CB); the first transplant was made in 1989 and in the last 25 years it has been widely applied in developed countries. CB banks have become an important reserve for these treatments and for regenerative cell therapy, due to their multiple advantages. Having a public CB bank in Cuba is a need for the development of our National Health System which will allow us to join our efforts with the international scientific community in the struggle for a better health care for our people and other countries of the world, particularly Latin America

Artículos de revisión: cultivos de expansión ex vivo de células madre a partir de sangre de cordón umbilical / Reviews: hematopoietic stem cell, ex vivo expansion from umbilical cordon blood

El éxito en el enfrentamiento a las hemopatías malignas depende de la erradicación de los clones tumorales por medio de la quimioterapia y la radioterapia. Sin embargo, en determinados pacientes la capacidad de curación se muestra limitada, y se requiere la sustitución de la función medular dañada por una nueva hematopoyesis sana, a través del trasplante de médula ósea (TMO). Este tipo de terapia celular puede contar ahora con donantes alternativos obtenidos a partir de la sangre de cordón umbilical (SCU) almacenada en bancos creados en varios países. Se ha comprobado la necesidad de promover un implante más rápido que disminuya la morbimortalidad relacionada con el procedimiento y permita la generalización de su uso, y se han propuesto estrategias basadas en la expansión de las células progenitoras hematopoyéticos (CPH) ex vivo, en cultivos a partir de SCU, lo que permite su uso en trasplantes con bajo contenido celular, y para diferenciar células pertenecientes a diferentes linajes hematopoyéticos, e incluso tejidos, con diferentes objetivos: trasplante hematopoyético, soporte de la recuperación a corto plazo, inmunoterapia, terapia génica, y diferenciación a tejidos mesenquimales. En esta revisión se explica cómo, de un producto habitualmente desechado, la SCU se ha convertido en una fuente de gran interés científico por la facilidad de su colecta, la fuente "ilimitada" de donantes, la calidad biológica de sus células madre cercanas a la época embrionaria y fetal del desarrollo, y la posibilidad de un uso amplio en diferentes estrategias de expansión ex vivo para terapia celular.

Alteraciones inmunológicas en pacientes hemofílicos tratados con crioprecipitado no asociadas con la infección por el virus de la inmunodeficiencia humana (VIH) / Immunologic alterations non-associated with infection by human immunodeficiency virus (HIV) in hemophilic patients treated with cryoprecipitado

Se informan las alteraciones inmunológicas detectadas en 27 pacientes con hemofilia A tratados con crioprecipitado de producción nacional y no asociadas a la infección por el virus de la inmodeficiencia humana cuendo se compararon con un grupo control de 50 donantes voluntarios de sangre. Se encontró una disminución estadísticamente significativamente (p < 0,05) en el porcentaje de células formadoras de roseta espontánea y un incremento significativo (p <0,01) en la roseta alogénica, también los pacientes mostraron un porcentaje disminuidos de linfocitos T CD4+ (p <0,001) y una relación T4/T8 promedio disminuida (p < 0,01) enn comparación con los controles. En la evaluación funcional, tanto la transformación linfoblástica de los linfocitos T, como la actividad citostóxica de las células NK y K de los pacientes, resultaron disminuidas (p < 0,01) con respecto al grupo control y se observó un incremento significativo en los niveles de IgG (p < 0,05) y de IgM (p < 0,01). Estos resultados indican la existencia de un estado de inmunodeficiencia subclínica en pacientes tratados con crioprecipitado seronegativos al virus de inminodeficeincia humana

Estandarización de una técnica de formación de rosetas con hematíes sensibilizados (EA) / Standardization of a rosette forming technique with sensibilized erythrocytes

Se informa que en 39 adultos sanos (30 hombres y 9 mujeres) con un promedio de edad de 31 años (rango de 22 a 46 años) se determinó la cifra de rosetas formadas por neutrófilos (RFN) con eritrocitos de carnero sensibilizados con antisuero de la clase IgG antieritrocitos de carnero producido en conejo. Se obtiene una media de 79,5% con una desviación estándar de 9,8% Se señala que estas cifras se corresponden con las comunicadas por otros autores. Se indica que la aplicación de esta técnica en nuestro laboratorio permite establecer los valores de referencia normales de RFN en adultos sanos, la aplicación de la misma a pacientes con infecciones recurrentes, procesos inflamatorios agudos y crónicos y utilizarla en síndromes mieloproliferativos, por lo que abre nuevas posibilidades en el estudio de los mecanismos de la inmunidad inespecífica

Estandarización de la técnica de citotoxicidad por células dependiente de anticuerpos / Standardization of cytotoxicity technique by antibody dependent cells

En 35 donantes sanos (24 hombres y 11 mujeres) se estandarizó una técnica capaz de medir la citotoxicidad mediada por células dependientes de anticuerpos (CMCDA), utilizando como diana células Chang previamente marcadas con Cr 51. Los índices de citotoxicidad (IC) obtenidos para las relaciones célula efectora/ célula diana 40:1, 20:1, 10:1 y 5:1, fueron los siguientes: 42,98ñ 16,76%; 30,0 ñ 13,11 %; 19,79 ñ 9,47 % y 12,62 ñ 6,61%, respectivamente. No se observaron diferencias significativas al comparar los IC de ambos sexos. Se obtuvo un aumento de la actividad citotóxica después de la depleción de las células adherentes y una amplia variabilidad de la CMCDA entre individuos diferentes

Anticuerpos anticitomegalovirus humano (CMV) en embarazadas a término y en recién nacidos vivos de Ciudad de La Habana / Human anticytomegalovirus (CMV) in pregnant women at term and live newborns in Havana city

Se estudian 220 muestras de sangre de embarazadas a término y 113 de sangre de cordón umbilical de recién nacidos vivos procedentes de 3 hospitales ginecoobstétricos de Ciudad de La Habana, para determinar la presencia de anticuerpos específicos de las clases IgG e IgM anticitomegalovirus humano (CMV), mediante una técnica de microanálisis inmunoenzimático cuantitativo (ELISA). Se encuentra el 57,7% de embarazadas seropositivas para la IgM y dl 1.08% para la IgM. Se informa que el estudio de la IgM específica en la sangre del cordón umbilical reveló el 0.8% de seropositividad. Se destaca que no se encontró asociación entre la presencia de anticuerpos y las variables de edad, raza, nivel escolar, ocupación y hospital de procedencia de las muestras