Research progress of chitosan and quaternized chitosan as vaccine adjuvant / 中国生物制品学杂志

@#Adjuvant is the key factor for many new vaccines to play a protective role. The addition of adjuvant can not only reduce the amount of antigen,but also increase the immunogenicity of its antigen,and stimulate the strong immune response of body. Chitosan,as the product of natural polysaccharide chitin removing part of acetyl group,has the characteristics of adhesion,permeability,biocompatibility and so on,and has been widely studied and applied as a vaccine adjuvant. As a novel adjuvant,it can not only help to induce cellular and humoral immunity,but also activate mucosal immunity. This review discussed the recent progress of chitosan and quaternized chitosan as vaccine adjuvants and the related mechanism.

Pathogenesis of Diabetes from Theory of Spleen Deficiency Causing Diabetes Based on Intestinal Innate Immunity / 中国实验方剂学杂志

In western medicine， the small intestine anatomically belongs to the digestive system and is also an important immune organ of the body. The innate immune system of the small intestine consists of a tissue barrier， innate immune cells， and innate immune molecules. The dysfunction of any part can cause metabolic disorders and eventually lead to diabetes. In the pathogenesis of diabetes， traditional Chinese medicine （TCM） has the theory of ''spleen deficiency causing diabetes''， which points out that the impaired spleen function results in inadequate transformation， impaired essence spread， and turbidity by essence accumulation， which is the core pathological link of blood glucose metabolism disorder in diabetes. In terms of the relationship between the small intestine and the spleen， the theory of TCM holds that the small intestine is located in the abdomen and the abdomen is dominated by the spleen. The digestion， absorption， and endocrine functions of the small intestine are also similar to the functions of spleen in governing movement and transformation and spreading essence by virtue of spleen Qi. Therefore， the anatomical and physiological functions of the small intestine in western medicine are closely related to the spleen in TCM. At the same time， the spleen is closely related to the innate immune function of the small intestine in TCM. The spleen participates in the generation and distribution of defense Qi， and the process of defense Qi playing the external function is similar to the process of the activation of the innate immune response. The spleen is also an important organ involved in fluid metabolism， which can cooperate with the lung and kidney to timely remove turbid fluid from the body. It can also work with the stomach as the hub of Qi ascending and descending and regulate the physiological activities of "clear Yang" and "turbid Yin"， so as to ensure the homeostasis of the internal environment of the body， which is the basis for maintaining the normal function of the innate immunity of the small intestine. Therefore， taking "spleen deficiency causing diabetes" as a bridge， the theory of TCM and western medicine were combined to explain the relationship between small intestinal innate immunity imbalance and the pathogenesis of diabetes from the perspective of TCM， which is helpful to understand the pathogenesis of diabetes in a deeper level and also provide a new perspective and new way for the prevention and treatment of this disease with TCM.

Research progress on immunomodulatory properties of periodontal ligament stem cells / 口腔疾病防治

@#Periodontal ligament stem cells (PDLSCs) have the potential for multidirectional differentiation and are the preferred seed cells for periodontal tissue regeneration. In recent years, a large number of studies have confirmed that PDLSCs also possess broad immunomodulatory properties. Therefore, in-depth exploration of their specific molecular mechanisms is of great significance for the treatment of periodontitis. The aim of this paper is to summarize the research progress on the regulation of PDLSCs on various immune cells and the effect of the inflammatory environment on the immune characteristics of PDLSCs to provide an important theoretical basis for the allotransplantation of PDLSCs and improve the therapeutic effect of periodontal tissue regeneration. Studies have shown that PDLSCs possess a certain degree of immunosuppressive effect on both innate and acquired immune cells, and inflammatory stimulation may lead to the impairment of the immunoregulatory properties of PDLSCs. However, current studies are mainly limited to in vitro cell tests and lack in-depth studies on the immunomodulatory effects of PDLSCs in vivo. In vivo studies based on cell lineage tracing and conditional gene knockout technology may become the main directions for future research.

Effect and Mechanism of Menispermi Rhizoma Total Alkaloids on Antiviral Infection / 中国实验方剂学杂志

ObjectiveTo investigate the antiviral effect of Menispermi Rhizoma total alkaloids and its relationship with the type Ⅰ interferon （IFN-Ⅰ） signaling pathway. MethodThe effects of Menispermi Rhizoma total alkaloids on the intracellular replication of influenza A virus （H1N1）， vesicular stomatitis virus （VSV）， and cerebral myocarditis virus （EMCV） were detected by fluorescent inverted microscope， flow cytometry， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and Western blot. A mouse model infected with H1N1 was constructed， and the mice were divided into a control group， H1N1 model group， Menispermi Rhizoma total alkaloids groups （10， 20， 30 mg·kg-1）， and oseltamivir group （40 mg·kg-1）， so as to study the effects on the weight and survival rate of infected mice. Real-time PCR was used to detect the activation effect of Menispermi Rhizoma total alkaloids on the IFN-Ⅰ pathway in cells， and the relationship between the antiviral effect of Menispermi Rhizoma total alkaloids in IFNAR1 knockout A549 cells （IFNAR1-/--A549） and IFN-Ⅰ pathway was detected. ResultCompared with the control group， the virus proliferated significantly in the model group （P<0.01）. Compared with the model group， Menispermi Rhizoma total alkaloids could significantly inhibit the replication of H1N1， VSV， and EMCV in vitro （P<0.01）， inhibit the weight loss of the mice infected with the H1N1 in vivo， and improve the survival rate of mice （P<0.05）. In addition， Menispermi Rhizoma total alkaloids activated the IFN-I pathway and relied on this pathway to exert the function of antiviral infection. ConclusionMenispermi Rhizoma total alkaloids exert antiviral effects in vivo and in vitro by activating the IFN-Ⅰ pathway.

Initiation and maintenance of acquired immunity in dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

Dry eye(DE)is a multifactorial ocular surface disorder arising from numerous pathologies. The pathogenesis of DE includes immune inflammation, oxidative stress, changes in tear film composition, corneal nerve abnormalities, and meibomian gland dysfunction. Among them, the immune inflammatory response is the most crucial in the pathogenesis of DE, which is regulated by both innate and acquired immune responses on the ocular surface. Multiple environmental stresses trigger the ocular surface innate immune response leading to corneal epithelial cell damage and inflammation and activate acquired immunity to participate in the ocular surface immune inflammatory response. Currently, multiple immune cells and inflammatory factors have been shown to be involved in the occurrence and development of DE. This article reviewed the immune progress and focused on the initiation and maintenance of acquired immunity in DE. Through the analysis of the latest viewpoints and research hot spots, we systematically introduced the immunomodulating mechanism underlying the mechanisms of the pathogenesis of DE and provided references for the prevention and treatment of DE.

Expression and Clinical Significance of MKI67 in Pancreatic Cancer / 肿瘤防治研究

Objectives To explore the expression, biological function, and mechanism of MKI67 in pancreatic cancer and its clinical significance. Methods The expression level, diagnosis, and prognostic value of MKI67 in pancreatic cancer were analyzed using public databases. We also investigated the association between the MKI67 with immune cell infiltration and immune checkpoint molecules. We analyzed the functional pathway enrichment to uncover the possible molecular mechanisms. qRT-PCR and Western blot assay were used to verify the expression of MKI67 mRNA and protein. Immunohistochemistry staining was used to detect the expression of MKI67 in tissue protein. Results The high expression of MKI67 was significantly associated with high histological grades and poor outcomes in pancreatic cancer. High MKI67 expression was correlated with poor prognosis of pancreatic cancer patients (P=0.009). MKI67 was an independent risk factor for the patient outcome (95%CI: 1.084-1.743, P<0.05). The MKI67 expression was positively correlated with the helper T cell 2 levels but negatively correlated with plasmacytoid DC, NK cells, mast cells, the T follicular helper, immune DC, and CD8 T cells. Conclusion MKI67 may serve as a biomarker for the diagnosis and prognosis of pancreatic cancer and the mechanism might be associated with immune escape or immunosuppression.

Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses

Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

Research progress on mitochondria regulating anti-tumor immunity / 浙江大学学报·医学版

Tumor cells adaptively reforge their metabolism to meet the demands of energy and biosynthesis. Mitochondria, pivotal organelles in the metabolic reprogramming of tumor cells, contribute to tumorigenesis and cancer progression significantly through various dysfunctions in both tumor and immune cells. Alterations in mitochondrial dynamics and metabolic signaling pathways exert crucial regulatory influence on the activation, proliferation, and differentiation of immune cells. The tumor microenvironment orchestrates the activation and functionality of tumor-infiltrating immune cells by reprogramming mitochondrial metabolism and inducing shifts in mitochondrial dynamics, thereby facilitating the establishment of a tumor immunosuppressive microenvironment. Stress-induced leakage of mitochondrial DNA contributes multifaceted regulatory effects on anti-tumor immune responses and the immunosuppressive microenvironment by activating multiple natural immune signals, including cGAS-STING, TLR9, and NLRP3. Moreover, mitochondrial DNA-mediated immunogenic cell death emerges as a promising avenue for anti-tumor immunotherapy. Additionally, mtROS, a crucial factor in tumorigenesis, drives the formation of tumor immunosuppressive microenvironment by changing the composition of immune cells within the tumor microenvironment. This review focuses on the intrinsic relationship between mitochondrial biology and anti-tumor immune responses from multiple angles. We expect to explore the core role of mitochondria in the dynamic interplay between the tumor and the host, in order to facilitate the development of targeted mitochondrial strategies for anti-tumor immunotherapy.

Cell-to-Cell Communications of cGAS-STING Pathway in Tumor Immune Microenvironment / 浙江大学学报·医学版

Targeting cGAS-STING pathway is a promising strategy in tumor treatment. The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of the second messenger 2'3'-cGAMP, activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING. Notably, in tumor immune microenvironment, key components of cGAS-STING pathway are transferred among neighboring cells. The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity. The membrane-based system, including extracellular vesicles transport, phagocytosis and membrane fusion transmit dsDNA, cGAMP and activated STING, enhancing the immune surveillance and inflammatory. The membrane proteins, including specific protein channel and intercellular gap junctions, transfer cGAMP and dsDNA, which are crucial to regulate immune responses. And the ligand-receptor interactions for interferons transmission amplifies the anti-tumor response. This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment. We further explore how these mechanisms modulate immunological processes and discuss potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Role of the IL8 rs4073 polymorphism in central nervous system toxicity in patients receiving multidrug-resistant tuberculosis treatment / Papel do polimorfismo rs4073 do gene IL8 na toxicidade do sistema nervoso central em pacientes em tratamento para tuberculose multirresistente

ABSTRACT Objective: To determine the role of the IL8 rs4073 polymorphism in predicting the risk of central nervous system (CNS) toxicity in patients receiving standard pharmacological treatment for multidrug-resistant tuberculosis (MDR-TB). Methods: A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed. Results: The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype. Conclusions: The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.

RESUMO Objetivo: Determinar o papel do polimorfismo rs4073 do gene IL8 na previsão do risco de toxicidade do sistema nervoso central (SNC) em pacientes em tratamento farmacológico padrão para tuberculose multirresistente (TBMR). Métodos: Amostras de sangue de uma coorte de 85 pacientes com TBMR que assinaram um termo de consentimento livre e esclarecido e que estavam recebendo tratamento com medicamentos antituberculosos de segunda linha foram amplificadas para o gene IL8 (rs4073) e genotipadas. Todos os pacientes foram avaliados clinicamente quanto a evidências de toxicidade do tratamento e categorizados de acordo com os achados. Foram avaliadas as associações brutas e ajustadas. Resultados: As principais queixas enquadraram-se nas seguintes categorias: toxicidade do SNC; toxicidade gastrointestinal; toxicidade cutânea; e toxicidade ocular e ototoxicidade. Sintomas de toxicidade gastrointestinal foram relatados por 59% dos pacientes, e sintomas de toxicidade do SNC foram relatados por 42,7%. Foram identificados os seguintes genótipos de IL8 (rs4073): AA, em 64 dos participantes; AT, em 7; TT, em 11. Houve associação significativa entre o modelo dominante de herança e toxicidade do SNC no modelo bruto (p = 0,024; OR = 3,57; IC95%: 1,18-10,76) e no ajustado (p = 0,031; OR = 3,92; IC95%: 1,13-13,58). O genótipo AT+TT do gene IL8 (rs4073) apresentou risco 3,92 vezes maior de toxicidade do SNC que o genótipo AA. Conclusões: O genótipo AT+TT tende a se associar a um maior risco de características clínicas adversas durante o tratamento da TBMR.

Corneal transplantation and concomitant SARS-CoV-2 infection: a case report / Transplante de córnea e infecção concomitante por SARS-CoV-2: relato de caso

ABSTRACT This report was aimed at presenting a case of neurotrophic keratitis and concomitant SARS-CoV-2 infection in a patient who has recently undergone a corneal DALK transplant. One month after corneal transplantation with adequate corneal epithelialization, the patient presented neurotrophic keratitis with a torpid course of the corneal transplant coinciding with a SARS-CoV-2 infection, with an excessive host immune response. In addition, the patient presented a re-positivization of nasopharyngeal polymerase chain reaction of SARS-CoV-2 with past disease after starting treatment with autologous serum eye drops. The implications at the ophthalmological level of SARS-CoV-2 infection may be clarified as the time the illness progresses and we learn more about how it acts. In this case, the disparity of signs and symptoms, the antecedent of corneal surgery, and the possibility of a herpetic infection as a cause of the primary leukoma suggested neurotrophic keratitis. Nonetheless, the involvement of systemic SARS-CoV-2 infection in the process, triggering an excessive host immune response at the corneal level with an increase in inflammatory cytokines must be taken into account. No relationship was found between treatment with autologous serum and re-positivization of nasopharyngeal polymerase chain reaction, presenting the patient a favorable response to treatment.

RESUMO O objetivo deste relato foi apresentar um caso de ceratite neurotrófica e infecção concomitante por SARS-CoV-2 em paciente submetido recentemente a transplante de córnea DALK. Um mês após o transplante de córnea com adequada epitelização da córnea, o paciente apresentou ceratite neurotrófica com curso tórpido do transplante de córnea, coincidindo com infecção por SARS-CoV-2, com resposta imune excessiva do hospedeiro. Além disso, o paciente apresentou repositivização da reação em cadeia da polimerase nasofaríngeo de SARS-CoV-2, com doença pregressa após iniciar tratamento com colírio de soro autólogo. As implicações a nível oftalmológico da infecção por SARS-CoV-2, podem ser esclarecidas à medida que a doença progride e aprendemos mais sobre sua forma de atuação. Neste caso, a disparidade de sinais e sintomas, o antecedente de cirurgia de córnea e a possibilidade de infecção herpética como causa do leucoma primário sugeriram ceratite neurotrófica. No entanto, deve-se levar em consideração o envolvimento da infecção sistêmica por SARS-CoV-2 no processo, desencadeando uma resposta imune excessiva do hospedeiro no nível da córnea, com aumento de citocinas inflamatórias. Não foi encontrada relação entre o tratamento com soro autólogo e a repositivização da reação em cadeia da polimerase nasofaríngea, apresentando ao paciente uma resposta favorável ao tratamento.

Revisão de literatura sobre os aspectos fisiológicos e nutricionais em bezerros alimentados com colostro acidificado / Literature review on physiological and nutritional aspects in calves fed acidified colostrum / Revisión de la literatura sobre aspectos fisiológicos y nutricionales en terneros alimentados con calostro acidificado

A colostragem é essencial para a saúde dos bezerros neonatos, uma vez que não há a transferência de imunidade através da placenta, ou seja, o contato inicial do organismo com anticorpos se dá através da primeira mamada, onde há transferência da imunidade passiva. Sendo assim, o objetivo do trabalho é revisar os benefícios da acidificação ou silagem do colostro para otimizar a conservação da dieta líquida em fazendas; analisar o impacto no desempenho de bezerros em comparação com o colostro tradicional refrigerado em aleitamentos convencionais. O volume ideal preconizado é, no mínimo, 10% do peso vivo do animal nas primeiras duas horas e mais 5% do peso vivo nas seis a oito horas seguintes a primeira ingestão, para que se obtenha um bom desenvolvimento durante o crescimento, caso contrário, a falta da administração do colostro nas primeiras horas de vida predispõe enfermidades, tais como pneumonia e diarreia, prejudicando assim a saúde e consequentemente o desempenho em relação a outros animais que receberam uma colostragem adequada. Problemas com a qualidade do colostro surgem devido ao armazenamento inadequado, especialmente em propriedades sem refrigeração. A falta de sistemas de congelamento resulta em administração de leite em temperatura ambiente por períodos prolongados, prejudicando assim a imunidade e nutrição dos bezerros durante a colostragem. Todavia, há alternativas para o problema tal como o fornecimento de silagem de colostro. Em alguns casos, o processo de acidificação demanda a adição de ácidos no leite, a fim de evitar o crescimento de microrganismos patogênicos. O principal aspecto positivo do leite acidificado é a manutenção em temperatura ambiente, ou seja, não há a necessidade de passar por processos de refrigeração.

Colostrum is essential for the health of newborn calves, since there is no transfer of immunity through the placenta, that is, the body's initial contact with antibodies occurs through the first feeding, where there is a transfer of passive immunity. Therefore, the objective of the work is to review the benefits of acidifying or colostrum silage to optimize the conservation of liquid diets on farms; analyze the impact on calf performance compared to traditional refrigerated colostrum in conventional sucklers. The recommended ideal volume is at least 10% of the animal's live weight in the first two hours and a further 5% of its live weight in the six to eight hours following the first ingestion, so that good development is achieved during growth, otherwise, the lack of colostrum administration in the first hours of life predisposes diseases, such as pneumonia and diarrhea, thus harming health and consequently performance in relation to other animals that received adequate colostrum. Problems with colostrum quality arise due to inadequate storage, especially in unrefrigerated properties. The lack of freezing systems results in milk being administered at room temperature for prolonged periods, thus damaging the calves immunity and nutrition during colostrum. However, there are alternatives to the problem such as the supply of colostrum silage. In some cases, the acidification process requires the addition of acids to the milk in order to prevent the growth of pathogenic microorganisms. The main positive aspect of acidified milk is that it remains at room temperature, that is, there is no need to undergo refrigeration processes.

El calostro es esencial para la salud de los terneros recién nacidos, ya que no existe transferencia de inmunidad a través de la placenta, es decir, el contacto inicial del cuerpo con los anticuerpos ocurre a través de la primera alimentación, donde existe una transferencia de inmunidad pasiva. Por lo tanto, el objetivo del trabajo es revisar los beneficios de acidificar o ensilar el calostro para optimizar la conservación de dietas líquidas en granjas; analizar el impacto en el rendimiento de los terneros en comparación con el calostro refrigerado tradicional en lechones convencionales. El volumen ideal recomendado es al menos el 10% del peso vivo del animal en las dos primeras horas y otro 5% de su peso vivo en las seis a ocho horas siguientes a la primera ingesta, para que se consiga un buen desarrollo durante el crecimiento, en caso contrario. la falta de administración de calostro en las primeras horas de vida predispone a enfermedades, como neumonía y diarrea, perjudicando la salud y consecuentemente el rendimiento en relación a otros animales que recibieron el calostro adecuado. Los problemas con la calidad del calostro surgen debido a un almacenamiento inadecuado, especialmente en propiedades no refrigeradas. La falta de sistemas de congelación provoca que la leche se administre a temperatura ambiente durante períodos prolongados, dañando así la inmunidad y la nutrición de los terneros durante el calostro. Sin embargo, existen alternativas al problema como el suministro de ensilaje de calostro. En algunos casos, el proceso de acidificación requiere la adición de ácidos a la leche para evitar el crecimiento de microorganismos patógenos. El principal aspecto positivo de la leche acidificada es que se mantiene a temperatura ambiente, es decir, no es necesario someterse a procesos de refrigeración.

La viruela sísmica aspectos relacionados a la fisiopatología, genoma, patogénesis, transmisión, replicación e inmunología / Aspects Related to pathophysiology, Genome, Pathogenesis, Transmission, Replication and Immunology of Monkeypox

Introducción: La viruela símica es una enfermedad zoonótica identificada por primera vez en 1958. El virus es un miembro del género Orthopoxvirus, de la familia Poxviridae. Infecta a una amplia variedad de mamíferos y se desconoce su reservorio natural. Objetivos: Describir los aspectos importantes relacionados a la fisiopatología, genoma, patogénesis, transmisión, replicación e inmunología de la viruela símica. Métodos: Se realizó una búsqueda de artículos originales, reportes de casos, revisiones bibliográficas y sistemáticas en el Portal Regional de la BVS, PubMed, Science, Nature y Lancet. Se consultaron los informes de la Organización Mundial de la Salud y la Organización Panamericana de la Salud sobre la viruela símica. Resultados: La propagación del virus de la viruela símica puede ocurrir a través del contacto cercano con lesiones, fluidos corporales, gotitas respiratorias y objetos contaminados. Una vez dentro del organismo, el virus infecta mucosas, células epiteliales y células inmunitarias de los tejidos adyacentes. El virus se replica y disemina rápidamente a través del sistema hemático y linfático. Las células T desempeñan un papel importante en la regulación de la respuesta inmunitaria contra el virus. Sin embargo, los Orthopoxvirus han desarrollado varios mecanismos para la evasión de la respuesta inmunitaria. Conclusiones: Los aspectos importantes descritos que se tuvieron en cuenta acerca de la transmisión de la viruela símica han tenido cambio significativo con el tiempo. El brote mundial de viruela símica de 2022 presentó una cadena de transmisión principalmente entre humanos asociada al contacto sexual(AU).

Introduction: Monkeypox is a zoonotic disease that was first identified in 1958. The virus is a member of Orthopoxvirus genus, of Poxviridae family. It infects wide variety of mammals and its natural reservoir is unknown. Objectives: To describe the important aspects related to pathophysiology, genome, pathogenesis, transmission, replication and immunology of monkeypox. Methods: A search of original articles, case reports, bibliographic and systematic reviews was carried out in VHL Regional Portal, PubMed, Science, Nature and Lancet. Reports from the World Health Organization and the Pan American Health Organization on monkeypox were consulted. Results: Spread of monkeypox virus can occur through close contact with lesions, body fluids, respiratory droplets, and contaminated objects. Once inside the body, the virus infects mucous membranes, epithelial cells and immune cells of adjacent tissues. The virus replicates and spreads rapidly through the blood and lymphatic system. T cells play an important role in regulating the immune response against the virus. However, Orthopoxviruses have developed several mechanisms to evade the immune response. Conclusions: The important aspects described, taken into account about monkeypox transmission, have significantly changed over time. 2022 global monkeypox outbreak presented a chain of transmission primarily among humans associated with sexual contact(AU)

Desenlace fatal en paciente con coinfección entre SARS-CoV-2 y dengue

La COVID-19, resultado de la infección por el SARS-CoV-2, se caracteriza por su afectación en las células alveolares del sistema respiratorio. Sin embargo, se ha documentado la posibilidad de una coinfección con el virus del dengue (DENV), lo que desencadena una respuesta inflamatoria sistémica severa. Esta respuesta inflamatoria intensificada conlleva a una liberación sustancial de ARN viral en el citoplasma celular, lo que amplifica la carga viral y agrava el daño pulmonar, provocando disfunción orgánica múltiple. En el caso del DENV, la infección induce una tormenta de citoquinas que incrementa la permeabilidad capilar, resultando en la fuga de plasma. El presente reporte tiene como objetivo describir un caso de un paciente adulto varón con coinfección por COVID-19 y dengue que tuvo un desenlace fatal.

COVID-19, a result of SARS-CoV-2 infection, is characterized by a primary impact on the alveolar cells of the respiratory system. However, the possibility of co-infection with dengue virus (DENV) has been documented, triggering a severe systemic inflammatory response. This heightened inflammatory response leads to a substantial release of viral RNA into the cellular cytoplasm, which amplifies the viral load and aggravates lung damage, causing multiple organ dysfunction. In the case of DENV, the infection induces a cytokine storm that increases capillary permeability, resulting in plasma leakage. The present report aims to describe a case of an adult male patient with COVID-19 and dengue co-infection who had a fatal outcome.

Consecuencias inmunológicas de la infección materna por VIH en el recién nacido no infectado / Immunologic consequences of maternal HIV infection in the uninfected newborn

Resumen Con la implementación de estrategias de cuidado perinatal, la tasa de transmisión vertical del virus de inmunodeficiencia humana (VIH) ha disminuido considerablemente en el mundo. A pesar de no mostrar cargas virales, los infantes expuestos al VIH no infectados (ENI) cursan en sus primeros meses de vida con mayores tasas de morbimortalidad. Esto se relaciona con enfermedades infecciosas por microorganismos oportunistas y menor respuesta a las vacunas en comparación con infantes sin exposición al virus, lo que sugiere alteraciones en su sistema inmunitario. En esta revisión abordamos diferentes evidencias de alteraciones en las respuestas inmunitarias innatas y adaptativas de infantes ENI que pudieran explicar esta disfuncionalidad inmunitaria. Adicionalmente, este conocimiento ayuda a entender cómo se desarrolla el sistema inmunitario desde los primeros momentos de gestación que servirán para encontrar alternativas de manejo y terapias para el bienestar de los infantes con esta condición.

Abstract With the implementation of perinatal care strategies, the rate of vertical transmission of human immunodeficiency virus (HIV) has decreased considerably worldwide. Despite the absence of viral loads, infants exposed to HIV not infected during gestation have higher morbidity and mortality rates. This is found to be related to infectious diseases by opportunistic microorganisms and lower response to vaccines in their first months of life compared to non-HIV exposed infants, suggesting alterations in their immune system. In this review we address different evidence of alterations in the innate and adaptive immune responses of HIV exposed infants that could explain their immune dysfunctionality. Additionally, this knowledge helps to understand how the immune system develops from the early stages of gestation and will serve to find management alternatives and therapies for the welfare of the infants with this condition.

Regulación de la respuesta inflamatoria dependiente de citocinas / Regulation of the inflammatory response dependent on cytokines i: en

Las citocinas son hormonas proteicas que permiten la comunicación intercelular, estimulan la activación de receptores de membrana específicos, poseen funciones de diferenciación celular y proliferación, participan en la quimiotaxis, así como en el crecimiento y la modulación de la secreción de inmunoglobulinas; no obstante, su acción principal está dada por la regulación del mecanismo de la inflamación. Las principales citocinas encargadas de esto son las interleucinas 1, 8, 12 y 16; además del factor de necrosis tumoral alfa e interferones, todas ellas proinflamatorias. Las interleucinas 6 y 12 también actúan en la inmunidad específica.

Cytokines are protein hormones that allow the intercellular communication, stimulate the activation of specific membrane receptors, have cell differentiation functions and proliferation, participate in the chemotaxis, as well as in the growth and modulation of immunoglobulin secretion; nevertheless, their main action is given by the regulation of the inflammation mechanism. The main cytokines in charge of this are interleukins 1, 8, 12 and 16, besides the tumor necrosis factor alpha and interferons, all of them proinflammatory. Interleukins 6 and 12 also act in the specific immunity.

Aspectos inmunológicos en preeclampsia / Immunologic Aspects in Preeclampsia

Resumen La preeclampsia es una patología con alta morbimortalidad a nivel mundial. En esta enfermedad la placenta es un órgano de choque donde la inflamación y la respuesta inmunológica generan el daño que se traduce en el cuadro clínico característico. La tríada clásica en preeclampsia está integrada por hipertensión, edema y proteinuria, por lo que se piensa que el endotelio debe estar afectado por la actividad inflamatoria-inmunológica. El sistema inmunológico actúa en el desarrollo del embarazo y lo hace a diferentes tiempos y regulando de manera fisiológica. Tanto componentes celulares como humorales de la respuesta innata y adquirida han sido estudiados en pacientes con preeclampsia y se ha determinado que su participación es decisiva en la fisiopatología de esta enfermedad. La participación del sistema inmunológico en la fisiopatología de la preeclampsia alcanza un alto nivel de complejidad pues interacciona con otros sistemas (coagulación, renal, cardiovascular y endocrinológico entre otros) favoreciendo así la enfermedad. Es por esto que el tratamiento debe ser integral, con una visión holística del padecimiento y que requiere de un equipo multidisciplinario, que actué armónicamente para así alcanzar el mayor éxito terapéutico con la menor frecuencia de secuelas para el binomio madre-feto o madre-recién nacido. En la gestación se desarrolla la denominada "tolerancia inmunológica del embarazo", en ese estado de tolerancia inmunológica las células B y T pueden reconocer antígenos específicos (por ejemplo, los paternos) y posteriormente activarse y generar la respuesta inmunológica, por lo que la preeclampsia podría ser considerada como una patología autoinmune, donde la perdida de la tolerancia inmunológica sería la piedra angular en la fisiopatología, conocer como limitar o regular esta activación celular anómala podría servir para proponer nuevos acercamientos terapéuticos y controlar así esta enfermedad.

Abstract Preeclampsia is a pathology with high morbidity and mortality worldwide. In this disease, the placenta is an organ of shock where inflammation and the immune response generate the damage that results in the characteristic clinical scenario. The classic triad in preeclampsia is made up of hypertension, edema, and proteinuria, so it is thought that the endothelium must be affected by inflammatory-immunological activity. The immune system acts in the development of pregnancy and does so at different times and regulating physiologically. Both, cellular and humoral components of the innate and acquired response have been studied in patients with preeclampsia and it has been determined that their participation is decisive in the pathophysiology of this disease. The involvement of the immune system in the pathophysiology of preeclampsia reaches a high level of complexity since it interacts with other systems (coagulation, renal, cardiovascular and endocrinological among others) thus favoring the disease. For this reason, treatment must be comprehensive, with a holistic vision of the condition and requires a multidisciplinary team that acts harmoniously to achieve the greatest therapeutic success with the least frequency of sequelae for the mother-fetus or mother-newborn dyads. During pregnancy, the so-called "immunological tolerance of pregnancy" develops, in this state of immunological tolerance the B and T cells can recognize specific antigens (for example, the paternal ones) and later activate and generate the immune response, which is why preeclampsia could being considered an autoimmune pathology, where the loss of immunological tolerance would be the cornerstone of pathophysiology, knowing how to limit or regulate this abnormal cell activation could help to propose new therapeutic approaches and thus control this disease.

Infections in patients with chronic lymphocytic leukemia

ABSTRACT Introduction: Infection is a major complication in patients with chronic lymphocytic leukemia (CLL). Newly diagnosed patients are at high risk of developing infection caused by encapsulated bacteria, such as Streptococcus pneumoniae and Haemophylus influenzae. Method and Results: However, once treatment is initiated, the spectrum of pathogens causing infection broadens, depending on the treatment regimens. With disease progression, cumulative immunosuppression occurs as a consequence of multiple treatment lines and the risk of infection further increases. On the other hand, the use of targeted therapies in the treatment of CLL have brought new risks of infection, with an increased incidence of invasive fungal diseases, particularly aspergillosis, in patients receiving Bruton kinase inhibitors. Conclusion: In this article, we review the epidemiology of infection in patients with CLL, taking into account the treatment regimen, and briefly discuss the management of infection.

Effect of Antiretroviral Therapy on Neutrophil Oxidative Burst in Children

Objective To ascertain the efect of human immunodefciency virus (HIV) infection, as well as, antiretroviral therapy (ART) on neutrophil oxidative burst in children. Methods Fifty-fve children living with HIV infection (30 receiving ART for?2 y, 25 treatment-naïve) and 30 healthy controls, aged 18 mo–18 y, were assessed for hemogram and neutrophil oxidative burst. The treatment-naïve children were followed up and the above tests were repeated after 6 mo of ART. Results Mean (SD) serum MPO activity at 6 mo after ART [32.1 (±19.9) U/L] was comparable to that at disease onset [17.2 (±23.0) U/L], although it was signifcantly higher compared to that in children on ART?2 y [13.3 (±15.8) U/L] and controls [12.1 (±11.9) U/L]. Median fuorescence intensity (MFI) of unstimulated DHR was highest at 6 mo after ART and in the treatment-naïve group, which was signifcantly higher than in the controls, as well as, children receiving ART?2 y. Stimulation index was highest in the control group [442.4 (341.9–562.9)], which was comparable to that in children on ART?2 y [304.2 (153.2–664.8)], but was signifcantly higher than the treatment-naïve cohort [266.1 (148.2–339.4)] and children on ART for 6 mo [318.8 (154.9–395.6)]. Conclusion A hyperinfammatory state caused by an increased serum myeloperoxidase enzyme activity and increased basal neutrophil oxidative burst was seen in untreated HIV infection and during initial 6 mo of ART. ART given for?2 y normalized the impaired neutrophilic phagocytic functions.

Dietary Immunomodulators - An Organic Boom in the Management of Chronic Diseases

Immunology involves all the defence mechanisms occurring in the body after the invasion of any infectious agent and the ability to resist this infection. The micronutrients like essential proteins, essential amino acids, vitamins (A, B6, B12, C, D, E and folic acid), fatty acids, minerals (iron, selenium, zinc and copper) and certain phytochemicals are of prime importance towards healthy immune system. In addition to these nutritional components, intestinal microflora and certain bacteria (probiotic bacteria) also play an important role in the modulation of healthy immune system. There is an ongoing trend of usage of immunomodulators to combat various chronic diseases like viral diseases, cancers, inflammatory and autoimmune diseases. This review focuses on various immunomodulators available in daily dietary meals, its positive and negative effects on immune system and its role in management of chronic illness as an adjunct to other modalities to achieve positive health benefits with minimal side effects.