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Aging is a gradual, continuous series of natural changes in biological, physiological, immunological, environmental, psychological, behavioral, and social processes. Aging entails changes in the immune system characterized by a decrease in thymic output of naïve lymphocytes, an accumulated chronic antigenic stress notably caused by chronic infections such as cytomegalovirus (CMV), and immune cell senescence with acquisition of an inflammatory senescence-associated secretory phenotype (SASP). For this reason, and due to the SASP originating from other tissues, aging is commonly accompanied by low-grade chronic inflammation, termed "inflammaging". After decades of accumulating evidence regarding age-related processes and chronic inflammation, the domain now appears mature enough to allow an integrative reinterpretation of old data. Here, we provide an overview of the topics discussed in a recent workshop "Aging and Chronic Inflammation" to which many of the major players in the field contributed. We highlight advances in systematic measurement and interpretation of biological markers of aging, as well as their implications for human health and longevity and the interventions that can be envisaged to maintain or improve immune function in older people.

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Lung cancer is the second cause of cancer related deaths worldwide. Chemotherapy and immunotherapy represent the current standard of care for advanced NSCLC. Platinum-based chemotherapy expands late-differentiated T cell populations. Therefore, immune restoration after chemotherapy to adjuvate the immunotherapeutic potential could be crucial. The aim of this study was to evaluate the effect of Biomodulina T (BT), a thymic polypeptide fraction, on peripheral lymphocytes subpopulations in the context of cancer disease. Additionally, whether these effects might induce a better response to CIMAvax-EGF, an epidermal growth factor (EGF) depleting immunotherapy. Eighteen advanced NSCLC patients were evaluated after being treated with platinum-based chemotherapy. We found that the frequency of terminally differentiated effector T cells re-expressing CD45RA (EMRA) CD4+ (p=0.0031) and CD8+ (p=0.0372) T cells decreased with the administration of BT, whereas CD4+ naive T cells increase in more than 70% of the patients. Remarkably, CD4+ and CD8+ T lymphocytes expressing programmed cell death receptor-1 (PD1) significantly decreased after BT administration (p=0.0005 and p<0.0001, respectively). We also found an enhancement of the anti-EGF antibody response with a large percentage of patients treated with CIMAvax-EGF reaching the good antibody response condition after four vaccine doses. Moreover, the median overall survival of patients treated with CIMAvax-EGF was 16.09 months. In conclusion, our results suggest that the immunorestoration generated by the administration of BT after first-line chemotherapy may induce a better immune response to CIMAvax-EGF that could translate into the clinical benefit of patients diagnosed with advanced NSCLC.

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BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic is a worldwide public health threat. Millions of people are at risk and older adults are more susceptible to developing the most serious manifestations of the disease, in part because of the effects of ageing on the immune system. Biomodulina T is an injectable immune modulator that has been licensed for use in Cuba for many years. OBJECTIVE: An open-label, uncontrolled trial was conducted to investigate whether or not it might be useful to prevent or modulate the serious effects of severe acute respiratory syndrome coronavirus 2 infections in older Cuban adults before the availability of vaccinations. METHODS: From April 12 to August 31, 2021, 1239 adults aged 60 years and older, unvaccinated against COVID-19 were recruited from the José Luis Dubrocq polyclinics, to receive Biomodulina T, 1 intramuscular 3 mL dose weekly for 6 weeks. Each person was visited at home weekly to be administered Biomodulina T. Once daily patients were seen by a medical student to collect information on any possible adverse events related to the medication as well as any symptoms of COVID-19. The possible usefulness of the intervention and its potential adverse events were assessed based on the number of older adults who became infected with COVID-19, and the severity of any symptoms reported or noted both during the 6-week treatment period and during an additional 6-week posttreatment observation period. RESULTS: Sixteen patients were diagnosed with symptomatic COVID-19 during the intervention using a specific reverse transcription polymerase chain reaction test. One patient died because of COVID-19. The most common preexisting diagnoses in treated patients included high blood pressure in 64.8%, diabetes mellitus in 19.85%, and ischemic cardiopathy in 13.88%. Biomodulina T was well tolerated. Only infrequent, mild, transient, and self-limited adverse events were identified. Both the incidence of COVID-19 infections and the overall mortality rate were lower in the treated patients than what was observed in the untreated general population of this Cuban province during the same time period. CONCLUSIONS: Although further, confirmatory, double-blind, controlled clinical trials are needed, Biomodulina T injections were well tolerated, and the results of this open, uncontrolled study suggest that it may have been useful to decrease the incidence and severity of symptomatic COVID-19 infection in these older Cuban adults. (Curr Ther Res Clin Exp. 2022; 82:XXX-XXX) © 2022 Elsevier HS Journals, Inc.

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Introducción: Durante las últimas décadas es evidente el aumento progresivo de los adultos mayores en Cuba. El proceso de envejecimiento provoca cambios en el sistema inmune que afectan su funcionamiento y desarrollo. Objetivo: Caracterizar parámetros hematológicos e inmunológicos mediante el hemograma completo en adultos mayores cubanos antes y después de la administración de la Biomodulina T®. Métodos: Se realizó un estudio descriptivo y observacional para evaluar el efecto de la Biomodulina T® sobre los parámetros del hemograma completo. Se utilizó el paquete estadístico GraphPad Prism (versión 6.00). Los datos que presentaban una distribución normal, se procesaron utilizando la t Student. La prueba de rangos con signo de Wilcoxon se empleó cuando los datos no cumplían una distribución normal, ambos para un nivel de significación de p < 0,05. Resultados: Predominaron las mujeres en relación a los hombres, que representó 27,6 por cientoHubo superioridad de adultos mayores de 76-80 años de edad. El conteo global de leucocitos se mantuvo dentro de parámetros normales y solo en 5 pacientes disminuyeron las plaquetas después de la administración de Biomodulina T. Estos resultados no fueron estadísticamente significativos. Conclusiones: Se demostró que el tratamiento con Biomodulina T® no modifica los diferentes parámetros del hemograma completo en el adulto mayor(AU)

Introduction: In the last decade it has been evident the rise in the older adults in Cuba. The process of aging causes changes in the immune system that affects the development and function. Objective: To characterize hematological and immunological parameters by means of the complete blood count in Cuban older adults before and after the administration of Biomodulin T® Materials and methods: A descriptive and observational study was to conducted to evaluate the use of Biomodulina T, the statistic package used was the GraphPad Prism (version 6.00). The data that showed a normal distribution were processed using the Student´s t test. The Wilcoxon´s signed range test with was used when the data did not comply with the normal distribution. Both for a signification level of p < 0.05. Results: Women predominated in relation to men, representing 27.6 percent. There was a predominance of older adults aged 76-80 years. The global leukocyte count remained within normal parameters and platelets decreased only in 5 patients after the administration of Biomodulina T, that results were not statistically significant. Conclusion: It was shown that the Biomodulina T did not modify the hemogram results in the elderly patients(AU)

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RESUMEN Para potenciar la inmunidad en personas con deterioro gradual del sistema inmune, causado por el envejecimiento o por padecer diferentes comorbilidades, el Grupo de las Industrias Biotecnológica y Farmacéutica de Cuba (BioCubaFarma) ha introducido el producto Biomodulina T. Este se ha utilizado, además, como parte del protocolo de prevención y para el tratamiento de pacientes positivos al SARS-CoV-2. La inmunidad dependiente del timo, incluida la inmunidad de células T y la producción de anticuerpos, disminuye con el tamaño del órgano en los adultos, lo que se conoce como "inmunosenescencia". La Biomodulina T es un extracto diafiltrado de timo de ternera; tiene una acción citorrestauradora e inmunomoduladora, que ha demostrado su eficacia en diferentes grupos de riesgo, dentro de los cuales los ancianos ocupan un lugar especial. En la actual situación epidemiológica nacional e internacional su inclusión en los protocolos de actuación es clave. El uso de este medicamento en un grupo vulnerable, como los ancianos, representa un horizonte esperanzador en tanto se avanza en la producción de vacunas nacionales que sean seguras y eficaces (AU).

ABSTRACT To boost immunity in people with gradual deterioration of the immune system, caused by aging or suffering from different comorbidities, the Group of the Biotechnology and Pharmaceutical Industries of Cuba (Biotechnology Farma) has introduced the product Biomodulin T. This has also been used as part of the prevention protocol and for the treatment of patients positive to SARS-CoV-2. Thymus-dependent immunity, including T-cell immunity and antibody production, decreases with organ size in adults, which is known as "immunosenescence." Biomodulin T is a diafiltered extract of veal thymus; it has a cytorestaurative and immunomodulatory action, which has demonstrated its effectiveness in different risk groups, within which elder people occupy a special place. In the current national and international epidemiological situation its inclusion in the protocols of action is significant. The use of this medication in a vulnerable group, such as elder people, represents a hopeful horizon as progress is made in the production of safe and effective national vaccines (AU).

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Introducción: La sepsis y el shock séptico se encuentran entre las principales causas de morbilidad y mortalidad en la población pediátrica a nivel mundial. Encontrar soluciones alternativas para combatirlas, mediante el desarrollo de agentes inmunomoduladores, ha atraído el interés de investigadores en los últimos 20 años; Cuba cuenta con Biomodulina T®, un potente inmunomodulador. Objetivo: Demostrar que existe evidencia científica que avale la realización de ensayos clínicos controlados para la incorporación de la Biomodulina T® en las pautas de tratamientos de la sepsis en las terapias intensivas pediátricas. Material y Métodos: Se realizó una búsqueda en las bases de datos Medline, PubMed, SciELO, Lilacs, Cochrane Library y Web of Science, entre marzo de 2019 y marzo de 2020; se seleccionaron los 47 artículos de mayor relevancia para esta investigación. Desarrollo: La inmunopatogenia del shock se centra en un fenotipo complejo y alteraciones funcionales, tanto del sistema inmune innato como del sistema adaptativo, con disminución del número de células efectoras, aumento de subpoblaciones de linfocitos inmunosupresores y agotamiento de células T. Biomodulina T® estimula la producción de linfocitos T y robustece la diferenciación de las células linfoblastoides del timo. La práctica médica sugiere que su administración podría ser una estrategia prometedora para la restauración inmune en pacientes pediátricos con shock séptico. Conclusiones: Existe evidencia científica que respalda el uso de Biomodulina T® en pacientes con shock séptico, lo cual sustenta la fiabilidad de realizar ensayos clínicos controlados en población pediátrica para su posterior incorporación en las pautas de tratamientos en las terapias intensivas(AU)

Introduction: Sepsis and septic shock are among the main causes of morbidity and mortality in the pediatric population worldwide. Finding alternative solutions to combat them through the development of immunomodulatory agents has attracted the interest of researchers in the last 20 years; Cuba has Biomodulina T®, a powerful immunomodulator. Objective: To demonstrate that there is scientific evidence that supports the conduction of controlled clinical trials for the incorporation of Biomodulina T® into the treatment guidelines for sepsis in pediatric intensive care therapies. Material and Methods: A search was carried out in the Medline, PubMed, SciELO, Lilacs, the Cochrane Library and the Web of Science databases between March 2019 and March 2020; the 47 most relevant articlesfor this research were selected. Development: The immunopathogenesis of shock focuses on a complex phenotype and functional alterations of both the innate and adaptive immune systems with a decrease in the number of effector cells, an increase in subpopulations of immunosuppressive lymphocytes, and depletion of T cells. Biomodulina T® stimulates the production of T lymphocytes and strengthens the differentiation of lymphoblastoid cells of the thymus; medical practice suggests that its administration could be a promising strategy for immune restoration in pediatric patients with septic shock. Conclusions: There is scientific evidence that supports the use of Biomodulina T® in patients with septic shock, which supports the reliability of conducting controlled clinical trials in the pediatric population for its subsequent incorporation into treatment guidelines in intensive care therapies(AU)

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Se realizó un Ensayo Clínico Controlado, fase II, aleatorizado y abierto en el Centro de Investigaciones sobre Longevidad, Envejecimiento y Salud, durante el período comprendido entre el año 2008 y 2009, con el objetivo de evaluar el efecto terapéutico de la Biomodulina T en presentación homeopática, con pacientes adultos mayores portadores de Enfermedad Pulmonar Obstructiva Crónica que sufrieran infección respiratoria a repetición. Se incluyó 100 pacientes, que dieron su consentimiento informado. Se distribuyeron en dos grupos: uno, recibió el tratamiento en estudio y el otro, el tratamiento control. La variable principal de respuesta fue la incidencia y severidad de sepsis respiratoria, durante y después del tratamiento. Se utilizó el paquete estadístico SPSS versión 13. La Biomodulina T en presentación homeopática tuvo buen efecto terapéutico en la reducción de infecciones respiratorias, así como en la disminución de las recidivas. Logró mejorar la comorbilidad en estos pacientes y mostró baja frecuencia de aparición de reacciones adversas.

A randomized, open, controlled Phase II Clinical Trial was perfomed at the Center of Investigations about Longevity, Aging and Health, from 2008 to 2009, aimed at assessing the therapeutic effect of Biomoduline T in homeopathic presentation, on senior adult patients with Chronic Obstructive Pulmonary Disease and suffering from recurrent respiratory infections. The study involved 100 patients, who gave their consent informed. The patients were equally distributed into two groups, one group received the trial treatment and the other the control treatment. The main response variable was the incidence and severity of respiratory sepsis, during and after the treatment. SPSS v. 13 statistical pack was used. Biomoduline T in homeopathic presentation had a good therapeutic effect on reducing respiratory infections and decreasing the recidives. It did improve the comorbility in these patients and showed low frequency in the apparition of adverse reactions.