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Braz. j. biol ; 83: e249913, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1339352


Abstract Aeromonas hydrophila is a cause of infectious disease outbreaks in carp species cultured in South Asian countries including Pakistan. This bacterium has gained resistance to a wide range of antibiotics and robust preventive measures are necessary to control its spread. No prior use of fish vaccines has been reported in Pakistan. The present study aims to develop and evaluate inactivated vaccines against local strain of A. hydrophila in Pakistan with alum-precipitate as adjuvant. The immunogenic potential of vaccine was evaluated in two Indian major carps (Rohu: Labeo rohita, Mori: Cirrhinus mrigala) and a Chinese carp (Grass carp: Ctenopharyngodon idella). Fish were vaccinated intraperitoneally followed by a challenge through immersion. Fish with an average age of 4-5 months were randomly distributed in three vaccinated groups with three vaccine concentrations of 108, 109 and 1010 colony forming unit (CFU)/ml and a control group. Fixed dose of 0.1ml was applied to each fish on 1st day and a booster dose at 15 days post-vaccination (DPV). Blood samples were collected on 14, 28, 35, 48 and 60 DPV to determine antibody titers in blood serum using compliment fixation test (CFT). Fish were challenged at 60 DPV with infectious A. hydrophila with 108 CFU/ml through immersion. Significantly higher levels of antibody titers were observed from 28 DPV in all vaccinated groups as compared to those in the control group. In challenge experiment the average RPS (relative percent survivability) was 71% for groups vaccinated with 109 and 1010 CFU/ml and 86% for 108 CFU/ml. Vaccine with 108 CFU/ml induced highest immune response followed by 109 and 1010 CFU/ml. The immune response of L. rohita and C. idella was better than that of C. mrigala. In general, normal histopathology was observed in different organs of vaccinated fish whereas minor deteriorative changes were found in fish vaccinated with higher concentrations of the vaccine.

Resumo Aeromonas hydrophila é uma causa de surtos de doenças infecciosas em espécies de carpas cultivadas em países do sul da Ásia, incluindo o Paquistão. Essa bactéria ganhou resistência a uma ampla gama de antibióticos, e medidas preventivas robustas são necessárias para controlar sua disseminação. Nenhum uso anterior de vacinas para peixes foi relatado no Paquistão. O presente estudo tem como objetivo desenvolver e avaliar vacinas inativadas contra cepa local de A. hydrophila no Paquistão com precipitado de alúmen como adjuvante. O potencial imunogênico da vacina foi avaliado em duas carpas principais indianas (Rohu: Labeo rohita, Mori: Cirrhinus mrigala) e uma carpa chinesa (Grass Carp: Ctenopharyngodon idella). Os peixes foram vacinados por via intraperitoneal, seguido de um desafio por imersão. Peixes com idade média de 4-5 meses foram distribuídos aleatoriamente em três grupos vacinados com três concentrações de vacina de 108, 109 e 1010 unidades formadoras de colônias (UFC) / ml e um grupo de controle. Foi aplicada dose fixa de 0,1ml em cada peixe no 1º dia e dose de reforço 15 dias pós-vacinação (DPV). Amostras de sangue foram coletadas em 14, 28, 35, 48 e 60 DPV para determinar os títulos de anticorpos no soro sanguíneo usando o teste de fixação de elogio (CFT). Os peixes foram desafiados a 60 DPV com infecciosa A. hydrophila com 108 CFU / ml por imersão. Níveis significativamente mais elevados de títulos de anticorpos foram observados em 28 DPV em todos os grupos vacinados, em comparação com aqueles no grupo de controle. Na experiência de desafio, o RPS médio (sobrevivência percentual relativa) foi de 71% para os grupos vacinados com 109 e 1010 CFU / ml e 86% para 108 CFU / ml. A vacina com 108 UFC / ml induziu a maior resposta imune seguida por 109 e 1010 UFC / ml. A resposta imune de L. rohita e C. idella foi melhor do que a de C. mrigala. Em geral, histopatologia normal foi observada em diferentes órgãos de peixes vacinados, enquanto pequenas alterações deteriorantes foram encontradas no grupo de controle e nos peixes vacinados com concentrações mais altas da vacina.

Animals , Carps , Gram-Negative Bacterial Infections/prevention & control , Gram-Negative Bacterial Infections/veterinary , Fish Diseases/prevention & control , Bacterial Vaccines , Aeromonas hydrophila , Alum Compounds , Immersion
Organ Transplantation ; (6): 253-2022.
Article in Chinese | WPRIM | ID: wpr-920857


Ocular graft-versus-host disease is one of the common complications after hematopoietic stem cell transplantation. Dry eye is the main clinical manifestation. Severe complications, such as corneal ulcer perforation and ocular surface failure may occur along with the progression of ocular graft-versus-host disease, which affects the visual acuity and quality of life of the patients. At present, multiple international researches and clinical guidelines for adult ocular graft-versus-host disease have been available. Nevertheless, pediatric ocular graft-versus-host disease has captivated insufficient attention, and relevant basic data and diagnostic criteria are still lacking. Children possess limited capability to express ocular symptoms, and lack of cooperation in clinical examination. In addition, ophthalmologists have insufficient understanding of this disease, which collectively increase the risk of missing diagnosis and misdiagnosis. In this article, the research progress on the pathogenesis, incidence, risk factors, clinical manifestations, diagnosis and treatment of pediatric ocular graft-versus-host disease was reviewed, aiming to provide ideas for strengthening clinical trials and expanding basic research of this disease in children.

Organ Transplantation ; (6): 161-2022.
Article in Chinese | WPRIM | ID: wpr-920845


3D bioprinting is an advanced manufacturing technology that utilizes biomaterials and bioactive components to manufacture artificial tissues and organs. It has been widely applied in multiple medical fields and possesses outstanding advantages in organ reconstruction. In recent years, 3D bioprinted organs have made an array of groundbreaking achievements. Nevertheless, it is still in the exploratory stage of research and development and still has bottleneck problems, which can not be applied in organ transplantation in vivo. In this article, the application of 3D printing technology in medicine, characteristics of 3D bioprinting technology, research hotspots and difficulties in bionic structure, functional reconstruction and immune response of 3D bioprinted organs, and the latest research progress on 3D bioprinting technology were illustrated, and the application prospect of 3D bioprinting technology in the field of organ reconstruction was elucidated, aiming to provide novel ideas for the research and clinical application of organ reconstruction and artificial organ reconstruction, and promote the development of organ transplantation and individualized medicine.

Acta Pharmaceutica Sinica ; (12): 46-63, 2022.
Article in Chinese | WPRIM | ID: wpr-913167


In recent years, immunotherapy has made great progress in clinical cancer therapy. However, the poor tumor specificity, low intra-tumoral penetration, and low cellular uptake in the systemic delivery of immunotherapeutic drugs lead to low efficacy and poor safety, limiting the development of immunotherapy. Active tumor-targeting nano drug delivery systems (aNDDS) can enhance the concentration of drugs in target cells through the interaction between surface-conjugated antibodies or ligands and the receptors on target cell membranes, providing a viable strategy for specific and efficient drug delivery. In addition, some specific types of cell membranes with the natural targeting ability have been exploited for the construction of biomimetic nanocarriers to improve the drug delivery efficiency. In view of the many advantages of active tumor-targeting nanocarriers, researchers also have designed a series of aNDDS for promoting antitumor immune responses and proved that they improved the efficacy and safety of immunotherapy. In this review, we summarize the recent progress on aNDDS for improving the tumor immunotherapy and look forward to the main challenges and future directions in this field.

Article in Chinese | WPRIM | ID: wpr-934034


Objective:To evaluate the immunogenicity of a novel influenza virus mRNA vaccine based on conserved antigens delivered by lipopolyplex (LPP) platform in a mouse model.Methods:Four copies of genes coding for extracellular domain of matrix 2 protein (M2e) and nucleoprotein (NP) of influenza A virus were synthetized after codon optimization. The fusion antigens were transcribed in vitro and delivered by LPP platform, named as LPP-4M2eNP. Expression of M2e and NP in eukaryotic cells was detected by immunofluorescence assay (IFA). BALB/c mice were inoculated intramuscularly twice with 10 μg or 30 μg LPP-4M2eNP vaccine at an interval of four weeks. Antibody response was detected by ELISA and cellular-mediated immunity (CMI) was detected by enzyme-linked immunospot assay (ELISPOT). Results:IFA showed that NP and M2e were expressed correctly in eukaryotic cells. Single dose immunization could induce significant antigen (NP, M2e)-specific CMI and antigen (NP, M2e)-specific antibody response was induced in mice with Th1 type bias after boost immunization. Moreover, NP-specific CMI was increased significantly after the second immunization, while no significant change in M2e-specific CMI was observed.Conclusions:Stronger CMI was triggered in mice by single dose of LPP-4M2eNP vaccine. Furthermore, robust humoral and cellular immune responses were induced after boost immunization. This study suggested that LPP-4M2eNP vaccine, which based on conserved antigen of influenza A and delivered by LPP platform, had great potential for development and application.

Article in Chinese | WPRIM | ID: wpr-934012


Objective:To investigate the effects of Ureaplasma urealyticum GrpE ( Uu-GrpE) on the maturation of dendritic cells and the polarization of T cells. Methods:Uu-GrpE was expressed and purified, and then identified by Western blot. The cytotoxicity of Uu-GrpE to mouse bone marrow-derived dendritic cells (BMDCs) was analyzed by LDH kit. After stimulating BMDCs with Uu-GrpE, the expression of costimulatory molecules, CD80, CD86 and major histocompatibility complex Ⅱ (MHCⅡ), on the surface of BMDCs was detected by flow cytometry, and ELISA was used to detect the cytokines such as IL-12p70, TNF-α, IL-1β and IL-6. CD4 + Na?ve T cells were isolated from mouse spleen tissues by magnetic beads. A co-culture system of BMDCs and Na?ve T cells was constructed to analyze the effects of GrpE-stimulated mature BMDCs (GrpE-BMDCs) on T cell proliferation and polarization towards Th1/Th2. Mice were immunized with GrpE-BMDCs through the tail vein, and the induced humoral and cellular immune responses were detected by ELISA and flow cytometry. Results:Uu-GrpE was successfully express and high purity BMDCs were isolated. Uu-GrpE could stimulate BMDCs to secrete cytokines such as IL-12p70, TNF-α, IL-1β and IL-6 without having cytotoxicity. Uu-GrpE significantly increased the expression of CD80 [mean flourscence indensity (MFI): (324.00±22.11) vs (91.03±10.95), P<0.01], CD86 [MFI: (1 176.00±51.39) vs (217.00±14.93), P<0.01] and MHCⅡ [MFI: (708.70±56.32) vs (185.70±16.77), P<0.01] on BMDCs. Compared to the GrpE-BMDCs only group and GrpE (boiled)-BMDCs+ T cell group, the GrpE-BMDCs+ T cell group showed significantly increased T cell proliferation [stimulation index: (7.25±0.21) vs(6.55±0.23) and (6.09±0.35), both P<0.05], and dramatically promoted T cell secretion of IL-2 and IFN-γ [IL-2: (145.60±14.67) pg/ml vs(55.92±3.12) pg/ml and (26.05±2.40) pg/ml, P<0.05 and P<0.01; IFN-γ: (267.20±37.80) pg/ml vs(146.70±20.65) pg/ml and(27.84±6.69) pg/ml, both P<0.05]. However, no significant change was observed in the expression of Th2-type cytokines. Moreover, the adoptive transfer of GrpE-BMDCs induced a Th1-type immune response. Conclusions:Uu-GrpE could stimulate the maturation and polarization of BMDCs. Moreover, it could induce Th1 immune response as a candidate protein vaccine for Ureaplasma urealyticum.

Frontiers of Medicine ; (4): 263-275, 2022.
Article in English | WPRIM | ID: wpr-929205


Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3+/CD4+/CD8+ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

COVID-19 , Clostridiales , Gastrointestinal Microbiome , Humans , Immunity , Leukocytes, Mononuclear , SARS-CoV-2
Article in Chinese | WPRIM | ID: wpr-942374


As a type of highly plastic innate immune cells, macrophages may be differentiated into M1 and M2 macrophages upon different stimuli, and M2 macrophages are involved in immune regulation, tissue remodeling and regeneration, and wound healing. Previous epidemiological studies have shown a significant negative correlation between the prevalence of helminth infections and the incidence of inflammatory diseases, such as allergy and autoimmune diseases. As a common type of intestinal helminths, hookworm infection may trigger high levels of type II host immune responses, with alternative activation of macrophages, which are effective to inhibit the development and progression of inflammatory diseases. This review summarizes the advances in alternative activation of macrophages in hookworm therapy for inflammatory diseases.

Journal of Clinical Hepatology ; (12): 1383-1386, 2022.
Article in Chinese | WPRIM | ID: wpr-924718


The phenomenon of N 6 -methyladenosine (m 6 A)-methylation is commonly observed in various tissues and cells of the human body and is the most common type of internal modification in eukaryotic mRNA. m 6 A-methylation is dynamic and reversible, which is regulated by various methyltransferases, demethylases, and m 6 A binding protein. Recent studies have shown that m 6 A modification can affect viral gene expression and plays an important role in the process of HBV infection. This article summarizes the current research status and mechanism of m 6 A-methylation, especially its association with HBV infection. This article also elaborates on the effect of m 6 A modification on HBV transcripts, reviews the research findings of m 6 A in immune response of HBV infection, and summarizes the effect of HBV infection on m 6 A modification in normal host hepatocytes and hepatitis B liver cancer, so as to discuss the development direction and potential value of m 6 A in HBV infection.

Organ Transplantation ; (6): 317-2022.
Article in Chinese | WPRIM | ID: wpr-923576


In recent years, the science and technology of organ transplantation have developed rapidly, which has been widely applied worldwide. However, multiple challenges remain to be resolved by clinicians, such as functional damage and immune rejection of transplant organs, immune deficiency caused by extensive use of immunosuppressants, chronic allograft dysfunction and adverse reactions. This article introduced relevant key research results published in 2021, taking the function and mechanism of immune cell subsets in the process of organ transplantation rejection or immune tolerance, and the research and application of new materials and drugs in organ transplantation as the main clues. The latest research progresses on regional immune response, especially the application of tissue-resident memory T cell in organ transplantation, were briefly summarized, and the future development of transplantation immunology was prospected.

Acta Pharmaceutica Sinica ; (12): 296-302, 2022.
Article in Chinese | WPRIM | ID: wpr-922938


Reactive oxygen species (ROS) is defined as the electron reduction product of oxygen with high reactivity which can maintain normal physiological functions and redox homeostasis. The tumor microenvironment is in a state of oxidative stress. ROS can affect multiple processes of tumor immune response by modulating the phenotype and functions of tumor cells and immune cells. With the rapid development of immunology, ROS-based tumor immunomodulation has been widely concerned and studied. In this review, the mechanism of ROS participating in tumor immune response is elaborated. Meanwhile, the research process and application of ROS in tumor immunomodulation in recent years are reviewed and analyzed.

Rev. bras. parasitol. vet ; 31(1): e014021, 2022. tab, graf
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1365761


Abstract This study aimed to evaluate foraging distance (FD) from the dung, parasitological and physiological factors in 18 Crioula Lanada lambs naturally infected by nematodes with three infection levels (IL) in a Voisin Grazing System. In the pre-experimental phase animal feces collection, deworming, observer training, animal adaptation and dung demarcation were carried out; in the experimental phase, grazing distance, feces, pasture and blood sampling. An initial exploratory analysis was carried out (Kruskal-Wallis test). Fixed predictors were selected with a cumulative logit regression model; an ordinal logistic regression mixed model identified influencing factors of ordinal responses for (i) FD, (ii) infective larvae quantity (L3). Animals approached the dung when the radiation or temperature were more intense (P < 0.05). Paddock entry/exit, IgG and L3 influenced FD over time (P < 0.05). L3, in turn, was influenced by IL, FEC and corpuscular volume (CV). In the High IL group, FD varied between 60-100 cm. Greater L3 and FEC were found in the High and Low IL from the 4th week (P < 0.05). Naturally infected Crioula Lanada lambs increased the distance from the dung, which was not related to IL but to the dynamics of solar radiation and parasitological and immunological factors.

Resumo O objetivo deste estudo foi avaliar a distância de forrageamento do bolo fecal (DF), fatores parasitológicos e fisiológicos em 18 cordeiros Crioula Lanada, naturalmente infectados por nematoides com três níveis de infecção (NI) em sistema Pastoreio Racional Voisin (PRV). Na fase pré-experimental, houve coleta de fezes dos animais, vermifugação, treinamento de observadores, adaptação dos animais e demarcação do bolo fecal; na fase experimental, distância, fezes, pastagem e sangue. Um modelo de regressão "logit" cumulativa selecionou preditores fixos; um modelo misto de regressão logística ordinal identificou fatores influenciadores das respostas ordinais para (i) DF (ii) quantidade de larva infectante (L3). Os cordeiros se aproximaram do bolo fecal quando a radiação ou temperatura foram mais intensas (P < 0,05). A entrada e a saída dos piquetes, a ingestão de L3 e IgG influenciaram DF (P < 0,05). L3 foi influenciada por NI, OPG e volume corpuscular. O grupo NI Alta variou a distância entre 60-100 cm. Maior L3 e a FEC foram encontrados nos grupos NI Alta e Baixa a partir da 4ª semana (P < 0,05). Cordeiros Crioula Lanada, naturalmente infectados, aumentaram a DF, sem relação com nível, de infecção, mas com a dinâmica da radiação solar e dos fatores parasitológicos e imunológicos.

Acta Pharmaceutica Sinica ; (12): 2364-2377, 2022.
Article in Chinese | WPRIM | ID: wpr-937032


The study aims to explore the intervention mechanism of Tingli Dazao Xiefei Decoction on asthma from the perspective of immune inflammation and intestinal flora, providing a theoretical basis for guiding clinical medication. The ovalbumin (OVA) asthmatic rat model was established by intraperitoneal injection of OVA sensitization solution and aerosol challenge, and divided into control (CON), model (M), dexamethasone group (DEX, 0.075 mg·kg-1) and Tingli Dazao Xiefei Decoction (TLDZ, 3.5 g·kg-1). Firstly, the effects of Tingli Dazao Xiefei Decoction on asthma symptoms of rats, lung and trachea pathological changes of asthmatic rats were observed by inducing cough and asthma experiment, phenol red excretion, hematoxylin-eosin staining (H&E), Masson and periodic acid Schiff (PAS) staining; the levels of transforming growth factor β1 (TGF-β1), interleukin (IL) 6 and IL-10 in rat serum and the levels of interferon γ (IFN-γ), immunoglobulin E (IgE), IL-4, IL-17A and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF) were detected by ELISA; the mRNA levels of IL-5, IL-13 and IL-33 in the lung were determined by qRT-PCR; the levels of macrophages and neutrophils in the spleen and the levels of natural killer cell (NK), helper T cell (Thc), dendritic cell (DC), regulatory T cell (Treg) and T helper cell 17 (Th17) in the peripheral blood were measured by flow cytometry combined with immunohistochemistry; the intestinal flora of asthmatic rats were analyzed by 16S rDNA high-throughput sequencing. Pathology and inflammatory results showed that Tingli Dazao Xiefei Decoction could effectively alleviate the asthma symptoms in rats, improve the pathological changes of lung tissue, reduce the production of goblet cells and collagen fibers, and reduce the inflammatory response in asthmatic rats; the results of immune cells showed that Tingli Dazao Xiefei Decoction could effectively increase the levels of NK, Thc, DC and Treg cells and reduce the levels of macrophages, neutrophils and Th17 cells in asthmatic rats; the results of intestinal flora showed that Tingli Dazao Xiefei Decoction could increase the levels of Lactobacillus, Ruminococcus, Christensenellaceae, Bifidobacterium and Eubacterium]_xylanophilum-group, and decrease the levels of Firmicutes, Desulfovibrio, Mucispirillum and Romboutsia in asthmatic rats. Therefore, it is speculated that Tingli Dazao Xiefei Decoction can improve the symptom of asthmatic rats by regulating the immune inflammation and intestinal flora in the asthmatic rats. All animal experiments in this article were approved by the Ethics Committee of Henan University of Chinese Medicine.

Int. j. med. surg. sci. (Print) ; 8(3): 1-18, sept. 2021. tab, ilus
Article in Spanish | LILACS | ID: biblio-1292534


mundo se encuentra en medio de la pandemia de la enfermedad por coronavirus 2019 (COVID-19). En la mayoría de los países, la tasa de mortalidad, así como, la severidad de la enfermedad es más alta en hombres que en mujeres. Este sesgo sexual sugiere que los hombres son más propensos a desarrollar complicaciones graves o a sucumbir a las mismas, lo que conduce a la muerte. Por lo tanto, es importante comprender los elementos biológicos basados en el sexo que inciden en la respuesta inmunitaria. El objetivo de ésta revisión fue hacer un análisis en relación a la evidencia disponible sobre los diferentes factores que permitirían explicar esta disparidad sexual. Abordamos las diferencias en la respuesta inmunitaria en ambos sexos tomando en cuenta el aspecto genético, hormonal y el papel del sistema renina-angiotensina. Para ello, se realizó una búsqueda minuciosa en diferentes bases de datos utilizando las siguientes palabras clave: (Diferencia de sexo, genética, hormonas sexuales, COVID-19, SARS-CoV-2, respuesta inmunitaria, inflamación, hombres, mujeres). Los resultados de nuestro análisis ofrecen una comprensión más clara sobre la influencia de las diferencias sexuales en la capacidad de respuesta a una infección, con especial énfasis en la infección por SARS-CoV-2. Conocer estos factores no solo ayudará a comprender mejor la patogenia de la COVID-19, sino, además, guiará el diseño de terapias efectivas para la medicina personalizada basada en las diferencias sexuales

The world is during the 2019 coronavirus disease pandemic (COVID-19). In most countries, the mortality rate, as well as, the severity of the disease is higher in men than in women. This sex bias suggests that men are more likely to develop severe complications or succumb to severe complications, leading to death. Therefore, it is important to understand the sex-based biological elements that influence the immune response. The aim of this review was to review the available evidence on the different factors that could explain this sex disparity. We addressed the differences in the immune response in both sexes taking into account genetic, hormonal and the role of the renin-angiotensin system. For this purpose, a thorough search was performed in different databases using the following keywords: (Sex difference, genetics, sex hormones, COVID-19, SARS-CoV-2, immune response, inflammation, men, women). The results of our analysis provide a clearer understanding on the influence of sex differences on the ability to respond to an infection, with special emphasis to SARS-CoV-2 infection. Knowing these factors will not only help to better understand the pathogenesis of COVID-19, but will also guide the design of effective therapies for personalized medicine based on sex differences.

Humans , Coronavirus Infections , COVID-19/complications , Pneumonia, Viral , X Chromosome , Severity of Illness Index , Sex Distribution , Betacoronavirus
Med. UIS ; 34(2): 61-75, mayo-ago. 2021. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1375820


RESUMEN La enfermedad por coronavirus 2019 (COVID-19) es causada por un nuevo betacoronavirus conocido como síndrome respiratorio agudo severo coronavirus-2 (SARS-CoV-2). Para el 22 de junio del 2021, el número de casos confirmados en todo el mundo había superado los 178 millones, con más de 3 millones de muertes. La fisiopatología de la COVID-19 a partir de la infección por SARS-CoV-2 no está del todo dilucidada. En el presente artículo se exponen los hallazgos encontrados después de la búsqueda en la literatura científica realizada en la base de datos PubMed entre octubre de 2020 y abril de 2021 en la cual se incluyeron 71 artículos, con el objetivo de la revisión fisiopatológica completa, detallada y actualizada del SARS-CoV-2, abordando temas como la caracterización y ciclo de vida del virus, el mecanismo de transmisión, la cinética viral y la respuesta inmune, junto con la dinámica fisiopatológica de la infección. MÉD.UIS.2021;34(2): 61-75.

ABSTRACT Coronavirus disease 2019 (COVID-19) is caused by a new betacoronavirus named as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). On June 22nd, 2021, the number of confirmed cases worldwide exceeded 178 million, resulting in more than 3 million deaths. The pathophysiology of COVID-19 from the infection of SARS-CoV-2 is not entirely elucidated. This review presents the findings after the research in the scientific literature carried out in the PubMed database between October 2020 and April 2021, in which 71 articles were included, with the aim of a complete, detailed and updated pathophysiological review of SARS-CoV-2, addressing issues such as the characterization and life cycle of the virus, the transmission mechanism, viral kinetics and immune response, along with the pathophysiological dynamics of the infection. MÉD.UIS.2021;34(2): 61-75.

Rev. cuba. invest. bioméd ; 40(2): e1014, 2021.
Article in Spanish | LILACS, CUMED | ID: biblio-1347464


Introducción. La COVID-19 es la enfermedad causada por el virus SARS-CoV-2. Aunque la mayoría de los pacientes presentan síntomas leves o moderados, un 5 por ciento desarrolla un síndrome respiratorio severo. Conocer la dinámica de la respuesta inmune en la infección por SARS-CoV-2 es esencial para el manejo adecuado de los pacientes. Objetivo. Describir los elementos esenciales de la dinámica de la respuesta inmune a la infección por SARS-CoV-2. Métodos: Se realizó una revisión de la literatura actualizada en bases de datos bibliográficas. Se consultaron 40 publicaciones. Se analizó la calidad y fiabilidad de los artículos seleccionados. Análisis e integración de la información: Durante los momentos iniciales de la respuesta inmune al SARS-CoV-2 predominan mecanismos innatos de defensa encaminados a eliminar el virus e impedir el avance de la enfermedad hacia la severidad. Si el sistema inmune no logra erradicar el virus ocurre una desregulación inmune que produce un daño importante por inflamación tisular. La inmunoterapia debe enfocarse en estimular la primera etapa (protectora) y suprimir la segunda. Una respuesta inmune adecuada es vital en el enfrentamiento a las infecciones por coronavirus. Conclusiones. La dinámica de la respuesta antiviral en los infectados por SARS-CoV-2 es uno de los elementos esenciales que condicionan la severidad de la enfermedad. La aparición de la tormenta de citocinas, producto de una desregulación inmune, se ha presentado como causa primaria del síndrome respiratorio severo observado en estos pacientes. Un mayor conocimiento de los mecanismos inmunopatogénicos es imprescindible para el desarrollo de medicamentos con alta eficacia.(AU)

Introduction: COVID-19 is the disease caused by the SARS-CoV-2 virus. Though most patients present mild or moderate symptoms, 5 percent develop severe respiratory syndrome. Awareness of the dynamics of the immune response to SARS-CoV-2 infection is essential for the appropriate management of patients. Objective: Describe the essential elements of the dynamics of the immune response to SARS-CoV-2 infection. Methods: A review was conducted of updated literature contained in bibliographic databases. A total 40 publications were consulted. An analysis was performed of the quality and reliability of the papers selected. Data analysis and integration: In the initial stage of the immune response to SARS-CoV-2 there is a predominance of innate defense mechanisms aimed at eliminating the virus and preventing the progress of the disease toward severity. If the immune system fails to eradicate the virus, immune dysregulation will occur and considerable damage will result from tissue inflammation. Immunotherapy should focus on stimulating the first (protective) stage and delete the second. An appropriate immune response is vital in the combat against coronavirus infections. Conclusions: The dynamics of the antiviral response in SARS-CoV-2 patients are essential elements conditioning the severity of the disease. Occurrence of the cytokine storm resulting from immune dysregulation has been cited as the primary cause of the severe respiratory syndrome developing in these patients. Better knowledge about the immunopathogenic mechanisms involved is indispensable to develop highly efficient drugs(AU)

Humans , Antiviral Agents , Pharmaceutical Preparations , Coronavirus Infections , Defense Mechanisms , Cytokine Release Syndrome , Immune System
Infectio ; 25(2): 94-100, abr.-jun. 2021. graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1250074


Resumen La infección por SARS-CoV-2 es hoy el principal problema de salud pública en el mundo. No es claro el papel de las citoquinas en la fisiopatología del COVID-19,que en algunos individuos presenta una progresión rápida, severa y mortal asociada con proinflamación sistémicos relacionada con coagulopatías y fallas multiorgánicas. En este estudio, evaluamos los niveles séricos de citoquinas y su correlación con IgM, IgG e IgA, en 24 muestras de individuos positivos y 8 muestras de individuos negativos, para SARS-CoV-2. Hallamos concentraciones significativamente menores de IFN-g, TNF, IL-2 e IL-4 y un aumento significativo de IL-6 en el grupo de infectados hospitalizados respecto a los no infectados, así como una tendencia significativa al aumento, para IgG e IgA en el mismo grupo de individuos, respecto a infectados asintomáticos. Nuestros datos soportan el papel de la IL-6 en la severidad de la enfermedad destacando su potencial papel como biomarcador en la prognosis de esta patología. También, soportan la hipótesis sobre la función de los anticuerpos en el control efectivo del patógeno; se observa una respuesta inmune humoral más débil, frente a la proteína de la nucleocápside viral, en individuos con un mejor curso de la enfermedad.

Abstract The emergency caused by the infection in humans of SARS-COV-2 and the clinical syndrome resulting from the infection (COVID-19) is a major public health crisis with global repercussions. Currently, the role of different cytokine profiles in the infection pathophysiology and its outcome remains unclear despite the coordina ted efforts of the scientific community. COVID-19 shows a rapid progression where the disease severity and mortality are linked to systemic pro-inflammatory pro cesses associated to a dysregulation in the cytokine production balance, resulting in blood clothing disorders and multiorgan failure. Here we evaluate the serum concentration for a cytokine panel as well as the antibody titers of IgM, IgG and IgA from 24 individuals who tested positive for SARS-CoV-2 by RT-PCR (divided into three separate groups according to disease severity) and eight RT-PCR-negative controls. Significantly lower concentrations of IFN-g, TNF, IL-2 and IL-4, and a higher production of IL-6 were observed in hospitalized COVID-19 patients when compared to SARS-CoV-2-negative individuals. Furthermore, a significant and sustained increase in the levels of IgG and IgA was found for the group of hospitalized patients compared to asymptomatic SARS-CoV-2-positive individuals. Our data support previous findings on the role of cytokines like IL-6 in the severity of the disease and highlight their potential use as biomarkers for the prognosis of COVID-19. Finally, we provide evidence supporting the potential function of the antibody response in the effective control of the virus, showing that a somehow weaker humoral immune response can be associated to milder forms of COVID-19.

Humans , Male , Cytokines , SARS-CoV-2 , COVID-19 , Biomarkers , Colombia , Immunity , Anti-Inflammatory Agents
Mem. Inst. Invest. Cienc. Salud (Impr.) ; 19(1)abr. 2021. tab, ilus
Article in Spanish | LILACS, BDNPAR | ID: biblio-1337691


El embarazo es la única causa natural de inmunización contra el sistema de Antígenos Leucocitarios Humano (HLA). Durante la gestación hay paso de leucocitos fetales a través de la placenta, lo que puede desencadenar en la madre una respuesta inmunológica contra los antígenos HLA fetales de origen paterno, con la consecuente producción de anticuerpos. El objetivo del estudio fue conocer la prevalencia de sensibilización a antígenos HLA inducida por embarazos en mujeres paraguayas y estudiar las características y especificidades de los anticuerpos encontrados. Realizamos un estudio descriptivo, prospectivo, de corte transversal de 319 mujeres paraguayas, que acudieron al Laboratorio Central de Salud Pública entre abril de 2017 y abril de 2018 utilizando la tecnología LUMINEX para la detección de anticuerpos anti- HLA. Se encontraron anticuerpos anti-HLA en 46% de las mujeres multíparas. Se detectaron anticuerpos contra todos los antígenos testados. La gran mayoría de los sueros resultaron ser poliespecíficos. Concluimos que al aumentar el número de gestas no solo aumenta la probabilidad de una mujer de desarrollar anticuerpos anti- HLA, sino que también parece aumentar la cantidad de especificidades desarrolladas y el título de los anticuerpos

Pregnancy is the only natural cause of immunization against the Human Leukocyte Antigen (HLA) system. During pregnancy, fetal leukocytes pass through the placenta, which can trigger an immunological response in the mother against the fetus paternal HLA antigens, with the consequent production of antibodies. The objective of this study was to determine the prevalence of pregnancy-induced HLA antigen sensitization in Paraguayan women and to study the characteristics and specificities of the antibodies found. We conducted a descriptive, prospective, cross-sectional study of 319 Paraguayan women, who attended the Central Laboratory of Public Health between April 2017 and April 2018 using LUMINEX technology to detect anti-HLA antibodies. We found anti-HLA antibodies in 46% of multiparous women. Antibodies against all tested antigens were detected. The vast majority of the sera exhibited multiple specificities. We conclude that increasing the number of gestations not only increases a woman's likelihood of developing anti-HLA antibodies, but it also appears to increase the number of developed specificities and titers of antibodies

Humans , Female , Pregnancy , Adult , HLA Antigens , Immunity , Antibodies , Pregnancy , Prevalence
Electron. j. biotechnol ; 50: 45-52, Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1292328


BACKGROUND: Lawsonia intracellularis remains a problem for the swine industry worldwide. Previously, we designed and obtained a vaccine candidate against this pathogen based on the chimeric proteins: OMP1c, OMP2c, and INVASc. These proteins formed inclusion bodies when expressed in E. coli, which induced humoral and cellular immune responses in vaccinated pigs. Also, protection was demonstrated after the challenge. In this study, we established a production process to increase the yields of the three antigens as a vaccine candidate. RESULTS: Batch and fed-batch fermentations were evaluated in different culture conditions using a 2 L bioreactor. A fed-batch culture with a modified Terrific broth medium containing glucose instead of glycerol, and induced with 0.75 mM IPTG at 8 h of culture (11 g/L of biomass) raised the volumetric yield to 627.1 mg/L. Under these culture conditions, plasmid-bearing cells increased by 10% at the induction time. High efficiency in cell disruption was obtained at passage six using a high-pressure homogenizer and a bead mill. The total antigen recovery was 64% (400 mg/L), with a purity degree of 70%. The antigens retained their immunogenicity in pigs, inducing high antibody titers. CONCLUSIONS: Considering that the antigen production process allowed an increment of more than 70-fold, this methodology constitutes a crucial step in the production of this vaccine candidate against L. intracellularis.

Animals , Swine Diseases/immunology , Bacterial Vaccines/immunology , Lawsonia Bacteria/immunology , Desulfovibrionaceae Infections/prevention & control , Swine , Swine Diseases/prevention & control , Bacterial Vaccines/administration & dosage , Vaccines, Synthetic , Cell Survival , Vaccination , Fermentation , Batch Cell Culture Techniques , Immunity
Article in Chinese | WPRIM | ID: wpr-843019


@#Oral cancer is one of the most common cancers that occur in the head and neck and can seriously affect the life span and living standard of oral cancer patients. Candida albicans (C. albicans) is the most common opportunistic pathogenic fungus in the oral cavity, shows pathogenicity and easily causes Candida infection when the host′s immune function is low. Recent studies have shown that C. albicans infection is closely related to oral cancer. This paper reviews the epidemiology of C. albicans infection in oral cancer patients, the influence of C. albicans infection on the occurrence and development of oral cancer and research on its mechanism. Existing studies have shown an increased risk of C. albicans infection in oral cancer patients, while C. albicans infection may promote the occurrence and development of oral cancer through mechanisms such as damaging the oral epithelium; producing carcinogens, including nitrosamine and acetaldehyde; and inducing a chronic inflammatory response and T helper cell 17 immune response. However, these mechanisms are still relatively superficial and lack sufficient direct evidence. In the future, additional in-depth studies are still needed to further clarify the cancer-promoting mechanisms of C. albicans and provide new ideas for the prevention and treatment of oral cancer.