The Significant Roles of Gut-lung Microbiota in Shaping and Regulating Immunity / 中山大学学报(医学科学版)

The interaction between microbes and the human immune system has long been a focus in biomedical research. Next-generation sequencing has revealed that in addition to gut microbiota， the respiratory tract also harbors microbial communities， forming an interconnected network with the gut microbiota through immune cells and active factors. This review aims to explore how the gut and lung microbiota regulate immune responses， including their roles in local and systemic immune modulation. It also delineates the immunological connections along the gut-lung axis. Further elucidating the influence of microbes on the immune system holds important clinical significance for understanding diseases and exploring novel diagnostic and therapeutic strategies.

Research progress of neuronal injury mediated by microglial activation and depression / 中国药理学通报

Depression is a common neurological disorder with high incidence, high recurrence and high disability, but its pathogenesis is unclear. In recent years, the protective and attacking effects of glial cells on neurons have become the frontier of neurological disease research. Neuronal injury caused by abnormal activation of microglia (MG) plays an important role in the pathogenesis of depression. In this paper, through literature retrieval by GeenMedical and CNKI, the relevant pathways and key targets of MG activation in depression are summarized so as to provide a theoretical basis for further clinical research.

Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Silencing GmWRKY33B genes leads to reduced disease resistance in soybean / 生物工程学报

The WRKYs are a group of plant-specific transcription factors that play important roles in defense responses. In this study, we silenced 2 GmWRKY33B homologous genes using a bean pod mosaic virus (BPMV) vector carrying a single fragment from the conserved region of the GmWRKY33B genes. Silencing GmWRKY33B did not result in morphological changes. However, significantly reduced resistances to Pseudomonas syringae pv. glycinea (Psg) and soybean mosaic virus (SMV) were observed in the GmWRKY33B-silenced plants, indicating a positive role of the GmWRKY33B genes in disease resistance. Kinase assay showed that silencing the GmWRKY33B genes significantly reduced the activation of GmMPK6, but not GmMPK3, in response to flg22 treatment. Reverse transcriptase PCR (RT-PCR) analysis of the genes encoding prenyltransferases (PTs), which are the key enzymes in the biosynthesis of glyceollin, showed that the Psg-induced expression of these genes was significantly reduced in the GmWRKY33B-silenced plants compared with the BPMV-0 empty vector plants, which correlated with the presence of the W-boxes in the promoter regions of these genes. Taken together, our results suggest that GmWRKY33Bs are involved in soybean immunity through regulating the activation of the kinase activity of GmMPK6 as well as through regulating the expression of the key genes encoding the biosynthesis of glyceollins.

Biological Connotation of Pathogenesis of Colorectal Cancer Due to Damp-heat Accumulation Based on Immune Response-intestinal Microbial Axis / 中国实验方剂学杂志

Colorectal cancer （CRC） is a malignant tumor of the intestinal tract with changes in bowel habits， blood in the stool， and pain as the main clinical manifestations. With the change in lifestyle and diet structure in recent years， the incidence of CRC has been increasing year by year. The pathogenesis of CRC is closely related to abnormal immune response and chronic inflammation， intestinal microbial dysbiosis， and the production of oncogenic metabolites. There is a two-way communication between the intestinal microbiota and the body's immunity， which not only plays a key role in maintaining the body's health but also has a close relationship with the development of diseases. An increasing number of studies have shown that abnormal immune responses accelerate the disease process by producing inflammatory factors， causing chronic inflammation in the body， disrupting the intestinal mucosal barrier， and increasing mucosal permeability， thus resulting in dysbiosis of the intestinal microbial ecology and a large number of pathogenic microorganisms and their metabolites. In addition， dysbiosis of intestinal microbes， by suppressing the normal immune response， leads to the disruption of multiple metabolic pathways in the body， affecting the internal and external stress response of the intestine， inducing inflammation， and thus producing disease. Therefore， the complex crosstalk mechanism between the immune response and intestinal microbial axis is closely related to the development of CRC. Based on traditional Chinese medicine theory and clinical research， it was found that dietary factors are an important causative factor in the development of CRC. The deficiency of positive energy is the root cause of the disease， and damp-heat accumulation is the key pathogenesis. Through modern medical and biological research， it is believed that abnormal immune response is the microscopic manifestation of damp-heat entrapment， while intestinal microbial dysbiosis is the biological basis of toxic injection into the large intestine， and in the pathogenesis of CRC， the imbalance of immune response-intestinal microbial axis is compatible with damp-heat accumulation in traditional Chinese medicine. This study aims to explore the biological connotation of CRC due to damp-heat accumulation from the immune response-intestinal microbial axis， so as to interpret the pathogenesis of CRC due to damp-heat accumulation with objective data and provide new ideas and theoretical basis for the pathogenesis and treatment strategies of CRC due to damp-heat accumulation.

Viable Leishmania parasites in the absence of an in vitro IFN-γ response in asymptomatic carriers

ABSTRACT Asymptomatic infection (the absence or inapparent signs and symptoms) has been observed in many endemic areas of leishmaniasis, however, little is known about the parasitological and immunological factors associated with this type of infection. This study aimed to identify the in vitro expression of IFN-γ in asymptomatic carriers of viable Leishmania parasites. Asymptomatic infection was identified using the Montenegro skin test in an at-risk population from Yucatan, Mexico. Parasite viability was evinced in the blood by 7SL RNA transcripts amplification. The expression of mRNA IFN-γ was analyzed in peripheral blood mononuclear cells stimulated with soluble Leishmania antigen, using RT-qPCR. Parasite viability was observed in 33.3 % (5/15) of asymptomatic subjects. No differences were found in the expression of IFN-γ between asymptomatic and healthy subjects, and no correlation was found between the presence of viable parasites and the expression of IFN-γ. This study demonstrates the persistence of Leishmania parasites in the absence of an in vitro IFN-γ response in asymptomatic carriers from Mexico.

Síndrome inflamatorio de reconstitución inmunológica (SIRS) en la salud reproductiva / Immune reconstitution inflammatory syndrome (IRIS) in reproductive health

Resumen El embarazo es un proceso que genera grandes cambios inmunitarios en los cuales participan los linfocitos T con respuestas proinflamatorias (Th1/Th17) y antiinflamatorias (Th2/Treg), con la finalidad de mantener el óptimo estado y desarrollo fetal. En la infección por VIH estos ambientes inmunológicos son afectados directamente con el descenso de las células TCD4. El uso de antirretrovirales (ART) ha permitido que las mujeres que viven con VIH puedan disminuir de manera importante la posibilidad de infectar a sus productos con el virus. El embarazo, enfermedades autoinmunes y el uso de ART son factores conocidos para el desarrollo del síndrome inflamatorio de reconstitución inmunológica debido a la recuperación abrupta de la respuesta inmunitaria. En esta revisión describimos parte de estos cambios en el embarazo y puerperio sin patología añadida, además proponemos un posible comportamiento en los perfiles Th1/Th2 en mujeres que viven con VIH que reciben ART y cursan el primer año posparto.

Abstract Pregnancy is a process which generate great immunologic changes with participation of T lymphocytes with inflammatory (Th1/Th17) and anti-inflammatory response (Th2/Treg), with the purpose of maintain the optimum condition and fetal development. In HIV infection this immunological ambient are affected directly due the decrease of T CD4 cells. The use of antiretrovirals (ART) has allowed that women living with HIV can decrease the possibility to infect their newborns with the virus. The pregnancy, autoimmune diseases, and the use of ART are known factors for the progress of immune reconstitution inflammatory syndrome due to the abrupt recovery of immune response. In this review we describe some of these changes during the pregnancy and puerperium without any disease added, furthermore we propose a possible behavior of Th1/Th2 profile in women who live with HIV and receive ART during the first year of postpartum.

Respuesta inmune en pacientes con diagnóstico de lepra

Introducción: La lepra es una entidad de expresión florida con afectación frecuente en el tegumento cutáneo y los nervios periféricos, por la predisposición que presenta el Mycobacterium leprae a estas estructuras. Las reacciones leprosas pueden aparecer en el curso de la enfermedad. Estas interrumpen la evolución crónica usual y la estabilidad clínica de los pacientes que la padecen. Objetivo: Caracterizar los estados reaccionales de la lepra. Materiales y métodos: Se realizó un estudio descriptivo en el período de enero de 2019 a septiembre de 2022, en pacientes que acudieron a la Consulta Provincial de Lepra en el Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas. El universo estuvo constituido por 8 pacientes que presentaron estados reaccionales en la etapa mencionada. Se recogieron de las historias clínicas variables como: edad, sexo, clasificación de la lepra según Ridley-Jopling, tipo de estado reaccional, forma clínica y momento de aparición. Resultados: La mayor frecuencia estuvo entre el rango de 50 a 64 años, con un 50 %. El sexo masculino representa el 62,5 %. Se mostró prevalencia de la lepra lepromatosa en el 62,5 %. La reacción tipo II y las formas graves fueron las más frecuentes, con un 62,5 % y 75 % respectivamente. Existió predominio de las reacciones leprosas durante y después del tratamiento, sin diferencias entre estas, con un 37,5 %. Conclusiones: La reacción tipo II y las formas graves de presentación fueron las predominantes en pacientes masculinos, representados en el grupo etario de 50 a 64 años. La forma clínica preponderante en estos eventos fue la lepromatosa.

Introduction: Leprosy is a floridly expressed entity with frequent involvement of the cutaneous integument and peripheral nerves due to the predisposition of Mycobacterium leprae to these structures. Leprosy reactions may appear during the course of the disease. These interrupt the usual chronic course and the clinical stability of patients suffering from the disease. Objective: To characterize the reactional states of leprosy. Materials and methods: A descriptive study was carried out from January 2019 to September 2022 in patients who attended the Provincial Leprosy Clinic at the Clinical Surgical University Hospital Comandante Faustino Pérez Hernández, in Matanzas. The universe consisted of 8 patients who presented reactional states in the aforementioned stage. The variables, collected from the clinical records, were: age, sex; classification of leprosy according to Ridley-Jopling, type of reactional state, clinical form and time of onset. Results: The highest frequency was between 50 and 64 years, with 50%. The male sex represents 62.5%. Lepromatous leprosy prevalence was shown in 62.5%. The type II reaction and severe forms were the most frequent with 62.5% and 75% respectively. There was predominance of leprosy reactions during and after treatment without differences between them, with 37.5%. Conclusions: The type II reaction with severe forms of presentation was predominant in male patients represented in the age group of 50 to 64 years. The predominant clinical form in these events was the lepromatous one.

Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (? or ?60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants – ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post- omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months

Respuesta inmunitaria anti-SARS-CoV-2: Infección Naturalvs. Vacunación / Anti-SARS-CoV-2 immune response: natural infection vs vaccination

Este trabajo es una revisión bibliográfica que compara la inmunidad anti-SARS-CoV-2 inducida por la infección natural y la inducida por vacunación, para entenderlas particularidades de la respuesta en cada caso, así como sus ventajas y desventajas. Se escogieron artículos que reportaran la medición de concentración de anticuerpos séricos, determinantes de inmunidad celular y/o evolución clínica de los pacientes. Se encontró que: A) Los pacientes recuperados de una infección por SARS-CoV-2 presentaron una respuesta mayor y más heterogénea de anticuerpos y células B de memoria que los pacientes vacunados, con un mayor número de linfocitos TCD4+, que cooperan con la diferenciación de linfocitos B y con la producción de anticuerpos neutralizantes. B) La vacunación previene la tormenta de citocinas asociada a la infección natural. C) Dos dosis de una vacuna basada en ARN mensajero logran una concentración de anticuerpos de clase IgG prácticamente igual a la de los pacientes severamente enfermos, pero sin el daño a los nódulos linfáticos asociado a la infección natural. D) Se puede aumentar el número de linfocitos B administrando dosis de refuerzo de la vacuna. Si bien, tanto la vacunación como la infección natural generan respuestas anti-SARS-CoV-2 significativas, la vacunación es el método más seguro para proteger a la población, pues evita el riesgo a la inmunopatología y a la mortalidad asociados con la infección natural. Más aún, la inmunidad híbrida (aquella que adquieren los pacientes que superaron la infección natural y fueron después vacunados) induce una producción de anticuerpos capaces de neutralizar por completo al SARS-CoV-2(AU)

This work is a bibliographic review that comparesanti-SARS-CoV-2 inmmune response induced by natural infección with that induced by vaccination, to understand theparticularities of each response, as well as their advantages and disadvantages. Research articles that reported levels of antibodies in serum, determinants of cellular inmmunity and/or clinical evolution of patients were chosen. It was found that: A) Pacients previously infected with SARS-CoV-2 presented a larger and more heterogeneous response of antibodies and memory B cells than vaccined patients, with a larger number of CD4+T cells that cooperate with the differentiation of B cells and production of neutralizing antibodies. B) Vaccination prevents the cytokine storm associated with natural infection. C) Two doses of an mRNA vaccine induced an IgG concentration nearly equal to severe ill patients but without the damage to lymph nodes associated with natural infection. D) B cell levels can be increased by giving booster doses of the vaccine. Althought both vaccination and natural infection generate significant anti-SARS-CoV-2 immune responses, vaccination is the safest method to protect general population, because it avoids the risk of immunopathology and mortality associated with natural infection. Futhermore, hybrid immunity (thatadquired by patients who overcame the natural infection and were later vaccinated), induces production of antibodies capable of completely neutralizing SARS-CoV-2(AU)

Vaccination strategies for people living with inborn errors of metabolism in Brazil

Abstract Objective: Through a literature review, make recommendations regarding immunizations in people living with Inborn Error of Metabolism (IEM) in Brazil, assess the possible impact on metabolic decompensations after immunization, and if this specific population may have an impaired immune response to vaccines. Source of data: The MeSH Terms vaccination OR vaccine OR immunization associated with the term inborn error of metabolism AND recommendation were used in combination with search databases. Only articles published after 1990, in the languages English, Spanish, French or Portuguese, human-related were included. Synthesis of data: A total of 44 articles were included to make the following recommendations. Individuals with IEMs need to be up to date with their immunizations. Regarding which vaccines should be offered, children and adults should follow the routine immunization schedules locally available, including the COVID-19 vaccines. The only exception is the rotavirus vaccine for hereditary fructose intolerance. The benefit of immunization outweighs the very low risk of metabolic decompensation. Since not all patients will have an adequate immune response, measuring antibody conversion and titers is recommended Conclusions: All patients should receive age-appropriate immunizations in their respective schedules without delays. The only situation when vaccination may be contraindicated is with oral rotavirus vaccine in hereditary fructose intolerance. Monitoring the levels of antibodies should be done to detect any immune dysfunction or the necessity for boosters. A personalized immunization schedule is ideal for patients with IEMs. The reference organizations could improve their recommendations to address all IEMs, not only some of them.

Covid-19 origin, transmission, immune response and treatment: A review

The novel 2019 Corona viruses are enveloped RNA genome virus, with a 79% genome similarity to the previous 2003 SARS Coronavirus-1 (SARS-CoV-1). Up to date the confirmed cases worldwide 11,327,790 And 209,509 in Saudi Arabia. The SARS-CoV-2 is a single strand RNA belongs to Beta corona virus. The phylogenetic analysis suspected that bats are the primary reservoir, however the zoonotic intermediate host that transfer SARS-CoV-2 to human is not identified. The glycoprotein spike exclusively on the SARS-CoVs-2 species binds to the host cell receptor through a region called receptor-binding domain (RBD) and mediates viral entry. SARS-CoV-2 targeting Angiotensin-converting enzyme 2 explain the reason behind the infection of the respiratory system especially. S glycoprotein is the most important protein of the virus while it is the best target for entry inhibitors, neutralizing antibody, and vaccine development. Besides the role of antibodies to eliminate virus separation, it can also reas viral entry in some virus species through a mechanism termed antibody-dependent enhancement (ADE) under certain conditions. This mechanism is the main block in the way of vaccine development against SARS-CoV 2. The balance between getting the induction of immunity protection and developing an enhanced susceptibility to virus infection after vaccination against SARS-CoV-2 is a highly sensitive and delicate approach and has a high risk. This novel version of the virus has many routes for infection, this may describe its ability to spread at a high rate and its high aggressivity compared to the previous one every year.

Evaluation of three alum-precipitated Aeromonas hydrophila vaccines administered to Labeo rohita, Cirrhinus mrigala and Ctenopharyngodon idella: immunokinetics, immersion challenge and histopathology / Avaliação de três vacinas de Aeromonas hydrophila precipitadas com alúmen administradas a Labeo rohita, Cirrhinus mrigala e Ctenopharyngodon idella: imunocinética, desafio de imersão e histopatologia

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.

Evaluation of three alum-precipitated Aeromonas hydrophila vaccines administered to Labeo rohita, Cirrhinus mrigala and Ctenopharyngodon idella: immunokinetics, immersion challenge and histopathology / Avaliação de três vacinas de Aeromonas hydrophila precipitadas com alúmen administradas a Labeo rohita, Cirrhinus mrigala e Ctenopharyngodon idella: imunocinética, desafio de imersão e histopatologia

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 [...].

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 [...].

Evaluation of three alum-precipitated Aeromonas hydrophila vaccines administered to Labeo rohita, Cirrhinus mrigala and Ctenopharyngodon idella: immunokinetics, immersion challenge and histopathology

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.

Autophagy and Inflammation in Fish / 中国生物化学与分子生物学报

Autophagy and inflammation are the important physiological reactions, especially in innate immunity. Autophagy, as a conservative metabolic process, can degrade its own disorder components through lysosomes to maintain cell homeostasis. Autophagy plays a pivotal role in degrading damaged organelles, resisting pathogenic infection and regulating inflammatory response. In the past decades, the study of autophagy in yeast and mammals has greatly increased our understanding for autophagy and its relationship with the diseases. In human, the regulation on autophagy levels can be used to prevent or treat neurodegenerative diseases, inflammatory diseases, tumors and various pathogenic microbial infections. However, in fish, the researches on autophagy and application are limited. Inflammation is a highly complex biological process, which is a natural defense response under the stimulation of ultraviolet, pathogen infection, oxidative stress and mechanical damage. Fish, as a lower vertebrate, has an incomplete acquired immune system. Innate immunity plays an important role in defensing against pathogen infection. Compared with higher vertebrate animals, although the researches on autophagy in fish cells were carried out lately, the great progress has been made in recent years on autophagy phenomenon, expression regulation of autophagy-related genes, and mechanism caused by pathogenic infection. As an important part of innate immunity, autophagy is involved in a variety of fish pathogenic infections, and fish diseases are usually accompanied by inflammatory reaction. In this review, we summarized the update findings in recent references on the autophagy and inflammatory response caused by pathogenic infection in fish, and the correlation between them, in order to deeply understand the correlation relationship between autophagy and inflammatory response in fish. This review could provide the guidance for understanding the immune mechanism of fish, and supply the foundation for developing new strategy to prevent and control fish disease.

Research Progress on the Influence of Bile Acids on the Immune Response of Hepatitis B Vaccine / 中山大学学报(医学科学版)

Hepatitis B vaccine （HepB） vaccination is the safest and most effective means of preventing hepatitis B virus （HBV） infection. HepB non-response is influenced by multiple factors， and solving the problem of poor immune response after HepB vaccination is of great significance for controlling HBV infection. Bile acids play an important role in human immune regulation， and whether bile acids have an effect on the HepB immune response has not been definitively studied. This article reviews the correlation between bile acids and HepB immune response， and provides a reference for further clarifying the pathogenesis and immunoprevention of bile acids in vaccine immunity.

Research progress on occupational exposure to carbon nanotubes and carbon nanotubes-induced pulmonary fibrosis / 中国职业医学

Carbon nanotube (CNT), as a new nanomaterial, is widely used in commercial and industrial production. The occupational exposure of workers involved in CNT production and manufacturing is gradually increasing. CNT mainly enters the human body through the respiratory system, and mainly exerts toxic effects on the respiratory system, including decreased lung function, lung inflammation, and pulmonary fibrosis. Pulmonary fibrosis, as one of the important diseases caused by CNT exposure, has attracted attention and been studied. The process of pulmonary fibrosis induced by CNT has four stages: acute pulmonary inflammatory response, structural destruction and parenchymal injury of lung tissue, impaired lung tissue repair and pulmonary fibrosis. The molecular mechanisms of CNT induced pulmonary fibrosis may be related to cell proliferation, epithelial-mesenchymal transition, fibroblast-myofibroblast differentiation, pulmonary inflammation, immune response and oxidative stress. In the future, it is needed to explore the pathogenesis of pulmonary fibrosis caused by CNT through animal experiments, and carry out large sample and multi-center epidemiological studies for verification.

Immunoprotective role of dendritic cells in Chlamydia muridarum respiratory infection / 中华微生物学和免疫学杂志

Objective:To investigate the role of dendritic cells (DC) in Chlamydia muridarum ( Cm) respiratory infection and their effect on adaptive immune response. Methods:C57BL/6 mice were exposed to 1×10 3 inclusion-forming units (IFU) of Cm through inhalation to establish the mouse model of Cm respiratory infection. The proportion of CD11c + MHCⅡ + DC and the expression of costimulatory molecules (CD40, CD80 and CD86) in spleen tissues were detected by flow cytometry on 0, 3 and 7 d after infection. The expression of IL-12p40, IL-10 and IL-6 at mRNA level in spleen tissues was detected by qPCR. Mouse splenic DC isolated on 7 d after Cm infection were sorted by magnetic beads and then transferred to recipient mice. Th1 response in the recipient mice was measured using intracellular cytokine staining 14 d after infection. Results:Cm respiratory infection induced massive infiltration of DC and promoted the expression of costimulatory molecules on splenic DC. The expression of IL-12 and IL-10 at mRNA level in splenic DC reached the peak on 3 d after infection. Transferring the splenic DC of Cm-infected mice into the recipient mice could alleviate the disease condition in the recipient mice after Cm infection with reduced Cm inclusion-forming units in lung tissues and significantly increased proportion of Th1 cells in lung and spleen tissues. Conclusions:Cm respiratory infection could induce the maturation and activation of DC, which promoted Th1 immune response. DC played an important role in Cm infection.

Analysis of LMP specific T cell immune response and clinical factors in stage III-IVa nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective:To explore the Epstein-Barr virus (EBV) latent infection membrane protein (LMP) 1 or LMP2 specific T cell immune response and clinical significance in stage III-IVa nasopharyngeal carcinoma (NPC), aiming to provide ideas and evidence for immunotherapy in NPC.Methods:Fifty-nine NPC patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from February 2018 to October 2020 for primary treatment were collected. Peripheral blood monocytes (PBMCs) were stimulated by LMP antigen. Intracellular cytokine staining and flow cytometry were applied to study the expression levels of IL-2, IL-13, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) from CD4 + T and CD8 + T cells, and then analyzed in conjunction with clinical factors. Results:The positive rates of total PBMCs to LMP1 and LMP2 in NPC patients were different. The positive rate of LMP1 specific CD4 + T cells was statistically higher in stage T 3-T 4 NPC than that in stage T 1-T 2 (51.0% vs. 10.0%, P=0.042). There were also differences in the expression of cytokines between LMP1 and LMP2, CD4 +T cells and CD8 +T cells. Survival analysis showed the 2-year and 3-year overall survival (OS) rates were 91.5% and 88.2%, and the 2-year and 3-year progression-free survival (PFS) rates were 83.3% and 75.3%. Univariate analysis suggested that smoking history, male and LMP1 stimulated IL-13 positive expression in CD4 + T cells affected the disease progression ( P=0.026, 0.045 and 0.006); multivariate analysis showed LMP1 stimulated IL-13 positive expression in CD4 + T cells and smoking history were the independent prognostic factors affecting PFS ( P=0.017, 0.019). Conclusions:LMP1 and LMP2 generate specific T-cell immune response in PBMCs of NPC patients, with differential expression in two T-cell subsets. LMP1 and LMP2 specific T cell immune response is associated with primary tumor size and metastatic lymph node volume. LMP1 stimulated IL-13 positive expression in CD4 + T cells and smoking history affects the disease progression.