Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children’s Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention. Objective incidence IEIrelated related studied Method Jan 202 Mar 2023 10 Childrens Children s NGS Results 1 15.7 157 15 7 (15. IEIassociated associated Xlinked X linked XLP, XLP , (XLP) B TNFRSF13B, TNFRSF13B TNFRSFB TNFRSF (TNFRSF13B) p11 APDS. APDS . (APDS) subsets 412 41 41. 18month month 18 eventfree event free EFS (EFS ORR (ORR 33.86% 3386 33 86 (33.86 vs 7326 73 26 73.2 0.011 0011 0 011 5294 52 94 52.94 8791 87 91 87.9 0002 002 0.002 respectively. respectively respectively) addition PD (PD 235 23 5 23. 44 4.4 0.006. 0006 0.006 006 0.006) Conclusion relapse intervention 20 15. (15 (XLP (TNFRSF13B p1 (APDS 33.86 338 8 (33.8 732 73. 0.01 001 01 529 9 52.9 879 87. 000 00 0.00 4. (1 33.8 (33. 0.0 52. ( 33. (33 0. (3

ABSTRACT Penaeus vannamei, or white shrimp, is an economically significant species that dominates shrimp production and represents a rapidly growing industry. However, the culture faces challenges due to high mortality rates due to bacterial and viral diseases. Unlike vertebrates, shrimp rely solely on their innate immunity for defense against pathogens. Introducing probiotics into shrimp culture can enhance growth, survival rates, and immune responses against disease outbreaks caused by pathogenic bacteria or viruses. Common diseases affecting shrimp farms include vibriosis, white spot disease, acute hepatopancreatic necrosis and black gill disease. These diseases can cause severe infections, which lead to high mortality rates. The application of probiotics, such as Bacillus cereus, B. licheniformis, B. subtilis, Lactobacillus sp., Paenibacillus, Pseudomonas sp., Pseudoaltermonas, and yeast, either through diet or direct administration, has demonstrated positive impacts on shrimp health, including enhanced growth, increased immunostimulation, improved gut microbiota, and better water quality parameters. In recent decades, aquafeed has explored effective solutions, such as microdiets, co-feeding (combining commercial feed and probiotics), and various microdiets types, to address aquaculture disease problems. Combining microdiets containing essential nutrients with probiotics has proven to be safer than antibiotics, which can adversely affect animals and the environment. However, further studies are needed to optimize the efficiency of feeding techniques by incorporating probiotics and commercial feed for disease resistance in penaeid shrimp culture. This review discusses commercial feeds and microdiets incorporated with probiotics for P. vannamei culture for growth and disease resistance to enhancement.

Abstract Objective: To assess the prevalence of chronic neutropenia (CN) and the clinical profile of patients with CN aged up to 18 years, followed in the pediatric hematology, rheumatology, or immunology outpatient clinic of a tertiary medical center from May 1, 2018, to 30 April 2019. Methods: Retrospective observational study carried out by collecting data from the patient’s medical charts. CN was defined as absolute neutrophil count (ANC) below 1.5 × 109/L lasting over three months. Autoimmune neutropenia (AIN) was defined by clinical criteria and an over twofold increase in ANC after glucocorticoid stimulation. AIN was considered secondary when associated with autoimmune or immunoregulatory disorders. Wilcoxon and Fisher’s exact tests were used to compare variables; the significance level was 5 %. Results: A total of 1,039 patients were evaluated; 217 (20 %) presented CN. Twenty-one (2 %) had AIN, classified as primary in 57 % of the cases. The average age at the onset of symptoms was 38.6 months. During follow-up, patients had 4.2 infections on average; frequency was higher among patients with secondary AIN (p = 003). Isolated neutropenia occurred in 43 % of the patients with AIN. Neutropenia resolved in eight (38 %) of the 21 patients with AIN within 19.6 months on average. Eight patients with secondary AIN met the criteria for Inborn Errors of Immunity. Conclusion: AIN prevalence was 2 %. Most cases were first evaluated by a pediatric immunologist or rheumatologist rather than a pediatric hematologist. This study highlights the need for a multidisciplinary approach involving a pediatric immunologist, rheumatologist, and hematologist. Objective (CN 1 years hematology rheumatology 2018 3 2019 Methods patient s charts (ANC 15 1. 109L L 109 (AIN stimulation disorders Fishers Fisher variables Results 1039 039 1,03 20 Twentyone Twenty one ( 386 38 6 38. followup, followup follow up, follow-up 42 4 4. p 003. 003 . 003) (3 196 19 19. Immunity Conclusion hematologist 201 10 103 03 1,0 00 0

Abstract Preterm delivery (PD) is the leading cause of perinatal morbidity/mortality in the world. Intrauterine infection is the most frequent origin of spontaneous PD (SPD) in a public hospital in Chile. There is evidence that vaginal ascending bacterial infection (ABI) causes intra-amniotic infection/inflammation, SPD, and adverse maternal and perinatal outcomes. This narrative review includes systematic reviews and cohort or case-control studies on the microbiota and immunological profile existing in the lower genital tract (LGT) of pregnant women prone to SPD due to ABI. There is consensus that in the LGT microbiota of this pregnant woman there is vaginal colonization with low abundance of Lactobacilli and/or decreased quality, due to racial and/or geographic, or genetic differences and dysregulation of immunological mechanisms of the LGT. These responses occur with greater intensity in patients with host risk factors, such as diabetes, obesity, stress, anxiety, and depression, causing recurrent LGT infections responsible for SPD and perinatal outcomes. Knowledge of the behavior of the microbiota and the immune system in these cases will allow effective therapies to prevent SPD and neonatal morbidity/mortality due to ABI.

Resumen El parto prematuro (PP) es la principal causa de morbilidad/mortalidad perinatal en el mundo. La infección intrauterina es el origen más frecuente del PP espontáneo (PPE) en un hospital público de Chile. Existe evidencia de que la infección bacteriana ascendente (IBA) produce la infección/inflamación intraamniótica, el PPE y los resultados adversos maternos y perinatales. Esta revisión narrativa incluye revisiones sistemáticas y estudios de cohorte o de caso-control sobre la microbiota y el perfil inmunológico existente en el tracto genital inferior (TGI) de la embarazada propensa a PPE por IBA. Existe consenso en que en la microbiota del TGI de esta gestante hay colonización vaginal con baja abundancia de lactobacilos y/o disminución de su calidad, por diferencias raciales y/o geográficas o genéticas y una desregulación de los mecanismos inmunológicos del TGI. Estas respuestas se presentan con mayor intensidad en pacientes con factores de riesgo del huésped, como diabetes, obesidad, estrés, ansiedad y depresión, originando infecciones recurrentes del TGI, responsables del PPE y de los resultados perinatales. El conocimiento del comportamiento de la microbiota y del sistema inmunitario en estos casos permitirá tener terapias eficaces para prevenir el PPE y la morbilidad/mortalidad neonatal por IBA.

Introduction: In general, inflammation stimulates the production and release of neutrophils and, at the same time, decreases the production of lymphocytes. Lymphopenia reflects that cell-mediated immunity is impaired, while neutrophilia represents a response to systemic inflammation in these cancers. Objective: To review the incidence of complications and postoperative survival rates in patients with bone metastases in long bones, correlating them with markers NLR and PLR. Method: Narrative review carried out collecting information published on virtual platforms in Portuguese and English, initially carried out by searching for descriptors related to the topic, which were: “lower extremity, surgery, metastasis, epidemiology, postoperative complications, neutrophils, lymphocytes, platelets”. The extension incorporated AND or OR, by title and/or summary, and full reading of the texts most related to the topic. Result: 21 articles were included. Conclusion: The higher both the NLR and PLR are associated with lower survival in patients with bone metastases when undergoing surgical treatment, especially after 3 months postoperatively. However, there is still no confirmation that they signal any outcome, favorable or not, in relation to postoperative complications.

Introdução : De um modo geral, a inflamação estimula a produção e liberação de neutrófilos e, ao mesmo tempo, diminui a produção de linfócitos. A linfopenia reflete que a imunidade mediada pelas células é prejudicada, enquanto a neutrofilia representa resposta à inflamação sistêmica nesses cânceres. Objetivo : Revisar nos pacientes com metástase óssea em ossos ao longo da incidência de complicações e taxas de sobrevida pós-operatória correlacionando-as com os marcadores NLR e PLR. Método : Revisão narrativa feita colhendo informações publicadas em plataformas virtuais em português e inglês inicialmente realizada por busca dos descritores relacionados ao tema que foram: “extremidade inferior, cirurgia, metástase, epidemiologia, complicações pós-operatórias, neutrófilos, linfócitos, plaquetas” e seus equivalentes em inglês “ extremidade inferior, cirurgia, metástase, epidemiologia, sobrevivência, complicações, neutrófilos, linfócitos, plaquetas sanguíneas ”. A extensão incorporou AND ou OR, pelo título e/ou resumo, e leitura na íntegra dos textos mais relacionados ao tema.  Resultado : Foram incluídos 21 artigos. Conclusão : Quanto maiores, tanto o NLR quanto o PLR estão associados à menor sobrevida em pacientes com MO quando submetidos ao tratamento cirúrgico, especialmente após 3 meses de pós-operatório. Contudo, ainda não há confirmação de que eles sinalizam algum estágio, positivo ou não, em relação às complicações pós-operatórias.

A dengue evoluiu de uma doença restrita a alguns países para um grave problema global de saúde pública, atingindo mais de 120 países nos últimos anos. No Brasil, após sua reintrodução em 1981, o país enfrentou diversas epidemias, com mais de 16 milhões de casos registrados até o momento. Em 2023, sob a vigência do fenômeno climático El Niño registrou-se uma das maiores epidemias de dengue no país, com mais de 1,6 milhões de casos notificados. Temperaturas e pluviosidade mais elevadas em conjunto com a circulação simultânea dos quatro sorotipos do vírus da dengue aumentaram ainda mais o risco de disseminação da doença em 2024, especialmente em populações sem imunidade para alguns dos sorotipos. Diante deste quadro, o Ministério da Saúde promoveu várias ações para enfrentar a situação, incluindo a instalação de uma Sala Nacional de Arboviroses e um Comitê de Operações de Emergência, repasses financeiros para apoiar estados e municípios em ações contingenciais de vigilância e prevenção de doenças, com ênfase no enfrentamento das arboviroses e investimentos em inovações para o controle da dengue, como vacinação e o método Wolbachia. Ainda assim, o primeiro trimestre de 2024 registrou um número de casos suspeitos de dengue superior ao de 2023, destacando a necessidade de aprimoramentos no monitoramento da situação epidemiológica para detecção precoce de epidemias e da preparação dos serviços de saúde para o cuidado dos casos com sinais de gravidade. Após mais de 40 anos de epidemias recorrentes, o controle efetivo da dengue no país requer ações sustentadas de prevenção por meio de estratégias inovadoras, envolvendo esforços coordenados de todas as esferas da gestão em saúde, juntamente com a participação ativa da população. Ações estruturais para a melhoria na cobertura de saneamento básico e para mitigação dos efeitos das mudanças climá

Dengue has evolved from a disease restricted to a few countries into a serious global public health issue, affecting over 120 countries in recent years. In Brazil, after its reintroduction in 1981, the country has faced several epidemics, with over 16 million cases registered to date. In 2023, under the influence of the El Niño climatic phenomenon, one of the largest epidemics occurred in the country, with over 1.6 million cases reported. High temperatures and precipitation in line with the simultaneous circulation of all four serotypes of the dengue virus increased the risk of disease spread in 2024, especially in populations without immunity to some of the serotypes. In such a scenario, the Ministry of Health undertook various actions to address the situation, including the establishment of a National Arbovirus Situation Room and an Emergency Operations Commitee, financial support to assist states and municipalities in contingency actions for disease surveillance and prevention, with an emphasis on combating arboviruses, and investments in innovations for dengue control, such as vaccination and the Wolbachia method. However, the number of notified dengue cases in the first trimester of 2024 supplanted the whole year of 2023, highlighting the need for a more effective monitoring of the epidemiological situation for early outbreak detection and the preparation of health services for the care of cases with signs of severity. After more than 40 years of recurrent dengue epidemics, the effective control of dengue requires sustained preventive actions using innovative strategies, with coordinated efforts at all levels of health management, along with active participation of the population. Structural actions to improve basic sanitation coverage and to mitigate the effects of climate change are critical conditions for reducing the burden of dengue in the population.

Abstract The evolutionary conserved link between coagulation and innate immunity is a biological process characterized by the thrombosis formation stimulus of immune cells and specific thrombosis-related molecules. In physiological settings, the relationship between the immune system and thrombosis facilitates the recognition of pathogens and damaged cells and inhibits pathogen proliferation. However, when deregulated, the interplay between hemostasis and innate immunity becomes a pathological process named immunothrombosis, which is at the basis of several infectious and inflammation-related thrombotic disorders, including coronavirus disease 2019 (COVID-19). In advanced stages, alterations in both coagulation and immune cell function due to extreme inflammation lead to an increase in blood coagulability, with high rates of thrombosis and mortality. Therefore, understanding underlying mechanisms in immunothrombosis has become decisive for the development of more efficient therapies to treat and prevent thrombosis in COVID-19 and in other thrombotic disorders. In this review, we outline the existing knowledge on the molecular and cellular processes involved in immunothrombosis, focusing on the role of neutrophil extracellular traps (NETs), platelets and the coagulation pathway. We also describe how the deregulation of hemostasis is associated with pathological conditions and can significantly aggravate a patient's condition, using COVID-19 as a clinical model. thrombosisrelated related molecules settings proliferation However deregulated inflammationrelated disorders 201 COVID19. COVID19 COVID 19 . (COVID-19) stages coagulability mortality Therefore COVID-1 review NETs, NETs , (NETs) pathway patients patient s condition model 20 COVID1 1 (COVID-19 COVID- (NETs 2 (COVID-1 (COVID- (COVID

Resumen La interacción entre la madre y el feto durante el embarazo se ha estudiado exhaustivamente. Una de estas interacciones es el microquimerismo, el cual se caracteriza por un intercambio madre-feto de células y material genético. Adicional a la gestación, la madre hereda más células por medio de la lactancia, donde se transfieren biocomponentes (células, anticuerpos y bacterias comensales) que juegan un papel importante en la adaptación del recién nacido al medio. Las consecuencias de este microquimerismo posparto genera beneficios directos en los primeros meses de vida, previniendo enfermedades e infecciones, induciendo tolerancia a moléculas inocuas, así como favoreciendo el entrenamiento inmunitario del recién nacido, con respuestas dirigidas y beneficios en la vida adulta. Es destacable que el microquimerismo materno podría interpretarse como un legado inmunológico en el neonato, el cual es perdurable para algunos de sus componentes y definitorio en el correcto desarrollo de la progenie.

Abstract The interaction between mother and fetus during pregnancy has been extensively studied. One of these interactions is the microchimerism, which is characterized by a mother-fetus exchange of cells and genetic material. In addition to gestation, the mother inherits more cells through lactation, in which biocomponents (cells, antibodies, and commensal bacteria) that play an important role in the adaptation of the newborn to the environment are transferred. The consequences of this post-partum microchimerism generate direct benefits in the first months of life, preventing diseases and infections, inducing tolerance to innocuous molecules, as well as favoring the immunological training of the newborn, with specialized responses and benefits in adult life. It is noteworthy that maternal microchimerism could be interpreted as an immunological legacy in the neonate, which is lasting for some of its components, and defining in the correct development of the progeny.

Abstract This paper aims to vindicate the expertise defense in light of the experimental philosophy of free will. My central argument is that the analogy strategy between philosophy and other domains is defensible, at least in the free will debate, because philosophical training contributes to the formation of philosophical intuition by enabling expert philosophers to understand philosophical issues correctly and to have philosophical intuitions about them. This paper will begin by deriving two requirements on the expertise defense from major criticisms of it. First, precisely how philosophical training contributes to the formation of philosophical intuitions requires explanation (Contribution); second, it must be explained how philosophical training immunizes philosophical intuitions from distorting factors (Immunity). I shall argue that the Contribution requirement is crucial for the expertise defense and that this requirement can be satisfied at least in the domain of free will: recent research shows that most novices are unable to understand determinism correctly, suggesting that having intuitions about determinism requires philosophical expertise. I then discuss how this proposal can be applied to other philosophical disciplines.

Resumen Este artículo pretende reivindicar la defensa de la pericia a la luz de la filosofía experimental del libre albedrío. Mi argumento central es que la estrategia de analogía entre la filosofía y otros dominios es defendible, al menos en el debate sobre el libre albedrío, porque la formación filosófica contribuye a la formación de la intuición filosófica al permitir a los filósofos expertos comprender correctamente las cuestiones filosóficas y tener intuiciones filosóficas sobre ellas. Este artículo comenzará derivando dos requisitos para la defensa de la pericia a partir de las principales críticas a la misma. En primer lugar, es preciso explicar con precisión cómo contribuye la formación filosófica a la creación de intuiciones filosóficas (Contribución); en segundo lugar, debe explicarse cómo la formación filosófica inmuniza a las intuiciones filosóficas frente a factores distorsionadores (Inmunidad). Argumentaré que el requisito de Contribución es crucial para la defensa de la pericia y que este requisito puede satisfacerse al menos en el dominio del libre albedrío: investigaciones recientes muestran que la mayoría de las personas inexpertas son incapaces de entender correctamente el determinismo, lo que sugiere que tener intuiciones sobre el determinismo requiere pericia filosófica. A continuación, discuto cómo esta propuesta puede aplicarse a otras disciplinas filosóficas.

ABSTRACT Cotton (Gossypium hirsutum L.) is economically important in Xinjiang, China, for many years; Verticillium wilt, arid climate, and soil salinization reduce cotton production, which has inhibited development of the cotton economy. Thus, creating a microbial agent specifically for cotton to resisting environmental stress is crucial. In this study, water dispersible granules strains (Bacillus tequilensis C-9 and B. sphingosporium A1) were screened for antagonistic bacteria of Verticillium dahliae from the rhizosphere soil of Ferula sinkiangensis K.M. Shen, and screened for carrier and auxiliary that could enhance the survival of strains A1+C-9. To test the efficacy and practicality of the water dispersible granules, their growth-promoting effect was examined. Meanwhile, bursts of reactive oxygen species and changes in the physiological indicators related to cotton growth were detected after the application of these granules to cotton that had been subjected to biotic and abiotic stresses to study the ability of the water dispersible granules to induce immunity in cotton. It was found that the treated group could increase the above-ground and below-ground fresh weight of cotton by 20.06% and 22.71% relative to the control group, and the biocontrol effect on cotton was increased by 46.55%. In salt and drought stress, catalase activity could be increased by 14.61% and 15.52%, respectively, relative to the control group. Comprehensive analyses showed that the application of water dispersible granules that contained A1+C-9 helped the cotton to grow and develop, inhibited V. dahliae from infecting cotton plants, reduced the damage from drought and salt stress, and increased the resilience of cotton to stress.

Biologically active compounds in most spices possess antimicrobial and other important biomedical properties. There have been huge demands for natural immunity boosters (spices and herbs), considering the recent global pandemic and challenges relating to drug-resistant pathogens. This study was designed to compare the efficacy of ginger, garlic and turmeric spices against some pathogenic microorganisms. Aqueous extraction of spices, antimicrobial sensitivity and minimum inhibitory concentration tests were done using standard microbiological methods. Bioactive compounds were estimated using the gas chromatography-mass spectrometry (GC-MS) method. Aqueous extracts of ginger inhibited the growth of all test isolates except Streptococcus pneumoniae, with inhibition zones ranging between 0.9 mm and 13.5 mm. Escherichia coli, S. pneumoniae and Haemophilus influenzae were resistant to turmeric extracts, while the extract of garlic inhibited only four of the test pathogens. Inhibition zones for turmeric ranged between 4.4 mm and 10.9 mm, while those for garlic were between 4.7 mm and 11.5 mm. All the spice extracts did not inhibit microbial growth at 10-40%. An antibiotic spectrum indicated that Bacillus sp. was resistant to all but one, nitrofurantoin, which also inhibited the growth of almost all pathogens, except H. influenzae, with zones ranging between 10.5 mm and 11.6 mm. All test pathogens were resistant to cloxacillin except E. coli (10.6 mm). The major phyto-active compounds present in ginger are 2-Butanone,4-(4-hydroxy-3-methoxyphenyl), 1,3-Cyclohexadiene and 1-(4-Hydroxy-3-methoxyphenyl). SIGNIFICANCE: Conclusively, ginger, turmeric and garlic have varied inhibitory activities against diverse organisms, indicating their antimicrobial properties; however, ginger showed a higher inhibitory effect and more diverse antimicrobial property amongst selected isolates. Furthermore, certain bioactive compounds of biomedical importance were present. We therefore recommend the use of these spices as alternative natural food preservatives against spoilage organisms, as well as potential natural sources for bioactive compounds in drug development against pathogens.

SARS-CoV-2, which caused the coronavirus pandemic in 2019 (COVID-19), is a beta-coronavirus, and its infection in host cells can activate innate and adaptive immune responses through the activation of several pro-inflammatory cytokines. Thus, in this study we established the relationship between the severity and immunopathology of COVID-19 through the main inflammatory cytokines. Results show that tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) and interleukins (IL), such as IL-6, are stimulated by the activation of T cell subsets, which results in immune-mediated cellular destruction. Several cytokines reduce the immune response and predispose to a pro-inflammatory and auto-reactive state, including IL-1β, IL-1RA, IL-7, IL-8, IL-9, IL-10, and associated inflammatory markers (LDH, GM-CSF and VEGF). These higher cytokine levels end up favoring tissue damage in multiple systems, including lungs, heart, gastrointestinal, brain, kidneys and other organs. Increasingly, a greater impact of the markers IL-6, ferritin, pro-calcitonin, lactic dehydrogenase, D-dimer and hypoalbuminemia was observed in patients with severe infection of the disease. In general, the data analyzed confirmed that COVID-19 severity is not caused simply by the viral infection, but rather by immune response and aberrant inflammation. In this way, this study allows a contribution to clinical practice, and it shows that it is essential to carry out in-depth studies about the immunopathology of COVID-19, in order to determine the severity markers involved in the pathogenesis of the viral infection.

O SARS-CoV-2, causador da doença coronavírus 2019 (COVID-19), é um beta-coronavírus, e sua infecção nas células do hospedeiro pode ativar respostas imunes inata e adaptativa, por meio da secreção de várias citocinas pró-inflamatórias. Assim, estabelecemos neste estudo a correlação da gravidade e imunopatologia da COVID-19 com as principais citocinas inflamatórias. Resultados mostram que o fator de necrose tumoral alfa (TNF-α), interferon-gama (IFN-γ) e interleucinas (IL), como a IL-6, são estimulados pela ativação de subconjuntos de células T, o que resulta em destruição celular imunomediada. Sendo que, diversas citocinas deprimem a resposta imune sadia, e predispõem a um estado pró-inflamatório e auto-reativo, dentre elas, IL-1β, IL-1RA, IL-7, IL-8, IL-9, IL-10, e os marcadores inflamatórios associados (LDH, GM-CSF e VEGF). Isso acaba por favorecer danos teciduais em múltiplos sistemas, como no pulmonar, cardíaco, gastrointestinal, cerebral, renal, dentre outros. Acrescenta-se que foi observado um impacto maior dos marcadores IL-6, ferritina, pró-calcitonina, desidrogenase láctica, D-dímero e hipoalbuminemia em pacientes com infecção grave da doença. De forma geral, pela análise de dados, verificou-se que a gravidade da doença COVID-19 parece ser modulada não apenas pela infecção viral, mas também por respostas imunes e inflamatórias aberrantes no hospedeiro. Dessa forma, este estudo permite contribuir para o auxílio da prática clínica, sendo imprescindível a realização de estudos aprofundados acerca da imunopatologia da COVID-19, a fim de que se determine os marcadores de gravidade envolvidos na patogênese da infecção viral.

ABSTRACT: This study evaluated the vaccine-induced serological response after administering four commercial formulations containing Bovine Viral Diarrhea Virus (BVDV) type-1, BVDV-2, and Bovine Herpesvirus type 1 (BoHV-1) to young heifers with circulating maternal antibody titers. The study also determined the anamnestic response to vaccinations after the complete metabolization of maternal antibodies when the calves reached six months. Eighty-seven Holstein heifers were selected and randomly distributed into four experimental groups based on the vaccine administered. The four vaccine-based experimental groups were as follows: vaccine A (n = 22), vaccine B (n = 22), vaccine C (n = 24), and vaccine D (n = 19), given on the 60th, 90th, and 180th day of life, respectively. Virus-neutralization (VN) tests were performed at baseline (day 60) and 30 days after administering the second (day 120) and third doses (day 210). We analyzed the effect of vaccine group (P ≤ 0.001), day of vaccination (P ≤ 0.001), and group versus vaccine day interaction (P ≤ 0.001) for antibody titers produced against BVDV-1, BVDV-2, and BoHV-1 using the PROC MIXED method (Statistical Analysis System -SAS 9.4). Antibody titers against BVDV-1, BVDV-2, and BoHV-1 were similar at baseline and on day 60 of life. The mean antibody titers were constant and persisted against BVDV-1 in heifers immunized with vaccines A and C. Heifers immunized with vaccine A alone had a similar effect against BVDV-2. Regarding BoHV-1, the antibody titers decreased between days 60 and 210 in groups B, C, and D. The antibody titer for heifers in group A also decreased between days 60 and day 120, and an intense increase in titers was observed on day 210. After being immunized with formulations B, C, and D, the frequency of animals with titers above protective levels for BVDV-1, BVDV-2, and BoHV-1 was very low or null. Indicators of anamnestic response were observed in heifers vaccinated with formulation A only. Therefore, it can be concluded that passive immunity negatively interferes with antibody production after vaccination. ABSTRACT vaccineinduced induced BVDV (BVDV type1, type1 1, type-1 BVDV2, BVDV2 2, 2 BVDV-2 BoHV1 BoHV (BoHV-1 months Eightyseven Eighty seven administered vaccinebased follows n 22, 22 , 22) 24, 24 24) 19, 19 19) 60th th 90th life respectively Virusneutralization neutralization VN (VN 3 120 . 210) P 0.001, 0001 0.001 0 001 BVDV1, BVDV1 BoHV- Statistical SAS 9.4. 94 9.4 9 4 9.4) 6 BVDV- BVDV2. 2. BoHV1, 21 null only Therefore type- (BoHV- 12 000 0.00 00 9. (BoHV 0.0 0.

RESUMO: O objetivo desse estudo foi avaliar a resposta sorológica induzida após vacinação com quatro formulações comerciais contendo o BVDV-1, BVDV-2 e BoHV-1 em novilhas jovens com títulos de anticorpos maternos circulantes, assim como analisar uma possível resposta anamnéstica em vacinações, após a completa metabolização dos anticorpos maternais aos seis meses de idade. Foram selecionadas 87 novilhas Holandesas, distribuídas aleatoriamente em quatro grupos experimentais de acordo com as vacinas: vacina A (n = 22), vacina B (n = 22), vacina C (n = 24) e vacina D (n = 19), aplicadas aos dias 60, 90 e 180 de vida. Testes de vírus-neutralização (VN) foram realizados no momento basal (D60) e 30 dias após a aplicação da 2ª dose (D120) e 3ª dose (D210). Observou-se efeito do grupo (P ≤ 0,001), dia da vacinação (P ≤ 0,001), e interação grupo versus dia (P ≤ 0,001) para os títulos de anticorpos produzidos contra o BVDV-1, BVDV-2 e BoHV-1, por meio do comando PROC MIXED (Statistical Analysis System, versão 9,4). Os títulos de anticorpos contra o BVDV-1, BVDV-2 e BoHV-1 eram semelhantes no momento basal aos 60 dias de vida. Os títulos médios de anticorpos foram constantes e persistentes contra o BVDV-1 nas novilhas imunizadas com as vacinas A e C, porém apenas a vacina A teve este mesmo perfil contra o BVDV-2. Em relação ao BoHV-1, os grupos B, C e D apresentaram queda nos títulos de anticorpos do D60 ao D210, enquanto as novilhas do grupo A apresentaram queda do D60 ao D120, com aumento intenso dos títulos no D210. A frequência de animais com títulos acima dos protetores contra o BVDV-1, BVDV-2 e BoHV-1 foram muito baixos ou nulos após as vacinações nos animais imunizados com as formulações B, C e D. Sugere-se que a imunidade passiva interferiu negativamente na indução de anticorpos pelas vacinas, observando-se indicadores de resposta anamnéstica apenas para as novilhas vacinadas com a formulação A. RESUMO BVDV1, BVDV1 BVDV 1, 1 BVDV2 2 BVDV- BoHV1 BoHV BoHV- circulantes idade 8 Holandesas n 22, 22 , 22) 24 19, 19 19) 9 18 vida vírusneutralização vírus neutralização VN (VN (D60 3 ª D120 (D120 D210 . (D210) Observouse Observou se P 0,001, 0001 0,001 0 001 BoHV1, Statistical System 9,4. 94 9,4 4 9,4) 6 BVDV2. 2. D6 Sugerese Sugere observandose observando (D6 D12 (D12 D21 (D210 000 0,00 00 9, (D D1 (D1 D2 (D21 0,0 (D2 0,

Abstract Liver’s contribution to innate immunity is eminent. However, uncontrolled inflammatory conditions predispose the liver to immune-mediated injury. Nigella sativa L. is traditionally implicated in infectious, inflammatory, metabolic and hepatorenal complications. This study aimed to evaluate the protective role of N. sativa seed extract (NSE) against concanavalin A (ConA)-induced acute immunological liver injury in mice. In vitro, NSE was subjected to quantitative phytochemical characterization and 1,1-diphenyl-2-picryhydrazyl (DPPH) analysis. In vivo, male Balb/c mice were pretreated with NSE (100, 200 and 400 mg/kg/day, p.o.) and pioglitazone (5 mg/kg/day, p.o.) for seven consecutive days. A single dose of ConA (12 mg/kg, i.v.) was injected and samples were collected for biochemical, histopathological and qRT-PCR analyses after 8 h of ConA injection. In vitro analysis showed considerable quantities of polyphenols and significant DPPH scavenging ability of NSE. In mice, ConA resulted in a significant (p<0.05) increase in liver injury markers (ALT, AST, ALP and TBil) and hepatic oxidative stress (SOD, CAT and MDA). Also, a substantial elevation of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in liver tissues was noticed. Furthermore, ConA markedly downregulated PPARγ and upregulated JAK2 and STAT3 expressions. In addition, considerably decreased expressions of Bcl-2 and increased Bax and Caspase-9 were observed. NSE demonstrated hepatoprotective effect in a dose-dependent manner through attenuating liver injury markers, oxidative stress parameters, pro-inflammatory cytokines levels as well as liver inflammation and hepatocyte apoptosis via modulating PPARγ/JAK2/STAT3 and Bcl-2/Bax/Caspase-9 pathways. Conclusively, the antioxidative, anti-inflammatory and anti-apoptotic actions of NSE could protect against acute immunological liver injury. Livers Liver s eminent However immunemediated immune mediated L infectious complications N (NSE ConAinduced induced 1,1diphenyl2picryhydrazyl 11diphenyl2picryhydrazyl diphenylpicryhydrazyl 1,1 diphenyl 2 picryhydrazyl 1 (DPPH vivo Balbc Balb c 100, 100 (100 20 40 mgkgday mg kg day mg/kg/day p.o. po p o 5 ( days 12 (1 mgkg mg/kg i.v. iv i v biochemical qRTPCR qRT PCR injection p<0.05 p005 0 05 (p<0.05 ALT, ALT (ALT AST TBil SOD, SOD (SOD MDA. MDA . MDA) Also proinflammatory pro TNFα, TNFα TNF α, α (TNF-α IL1β ILβ IL 1β β IL6 6 IL-6 noticed Furthermore JAK STAT addition Bcl2 Bcl Bcl- Caspase9 Caspase 9 Caspase- observed dosedependent dependent parameters PPARγJAK2STAT3 PPARγJAKSTAT PPARγ/JAK2/STAT Bcl2/Bax/Caspase9 Bcl2BaxCaspase9 BclBaxCaspase 2/Bax/Caspase Bcl-2/Bax/Caspase- pathways Conclusively antioxidative antiinflammatory anti antiapoptotic apoptotic 1diphenyl2picryhydrazyl 11 1, 10 (10 4 p.o i.v p<0.0 p00 (p<0.0 IL- PPARγJAK PPARγJAK2STAT Bcl2/Bax/Caspase BaxCaspase Bcl2BaxCaspase 2BaxCaspase Bcl-2/Bax/Caspase p<0. p0 (p<0. p<0 (p<0 p< (p< (p

Abstract Background ST-segment elevation myocardial infarction (STEMI) is one of the leading causes of fatal cardiovascular diseases, which have been the prime cause of mortality worldwide. Diagnosis in the early phase would benefit clinical intervention and prognosis, but the exploration of the biomarkers of STEMI is still lacking. Objectives In this study, we conducted a bioinformatics analysis to identify potential crucial biomarkers in the progress of STEMI. Methods We obtained GSE59867 for STEMI and stable coronary artery disease (SCAD) patients. Differentially expressed genes (DEGs) were screened with the threshold of |log2fold change| > 0.5 and p <0.05. Based on these genes, we conducted enrichment analysis to explore the potential relevance between genes and to screen hub genes. Subsequently, hub genes were analyzed to detect related miRNAs and DAVID to detect transcription factors for further analysis. Finally, GSE62646 was utilized to assess DEGs specificity, with genes demonstrating AUC results exceeding 75%, indicating their potential as candidate biomarkers. Results 133 DEGs between SCAD and STEMI were obtained. Then, the PPI network of DEGs was constructed using String and Cytoscape, and further analysis determined hub genes and 6 molecular complexes. Functional enrichment analysis of the DEGs suggests that pathways related to inflammation, metabolism, and immunity play a pivotal role in the progression from SCAD to STEMI. Besides, related-miRNAs were predicted, has-miR-124, has-miR-130a/b, and has-miR-301a/b regulated the expression of the largest number of genes. Meanwhile, Transcription factors analysis indicate that EVI1, AML1, GATA1, and PPARG are the most enriched gene. Finally, ROC curves demonstrate that MS4A3, KLRC4, KLRD1, AQP9, and CD14 exhibit both high sensitivity and specificity in predicting STEMI. Conclusions This study revealed that immunity, metabolism, and inflammation are involved in the development of STEMI derived from SCAD, and 6 genes, including MS4A3, KLRC4, KLRD1, AQP9, CD14, and CCR1, could be employed as candidate biomarkers to STEMI. STsegment ST segment (STEMI diseases worldwide prognosis lacking GSE GSE5986 (SCAD patients (DEGs log2fold logfold log fold change 05 0 5 0. 005 <0.05 Subsequently Finally GSE6264 75 75% 13 Then Cytoscape complexes metabolism Besides relatedmiRNAs predicted hasmiR124, hasmiR124 hasmiR has miR 124, 124 has-miR-124 hasmiR130a/b, hasmiR130ab hasmiRab 130a/b, 130a b has-miR-130a/b hasmiR301a/b hasmiR301ab 301a/b 301a Meanwhile EVI1 EVI AML1 AML GATA1 GATA gene MS4A3 MSA MS A KLRC4 KLRC KLRD1 KLRD AQP9 AQP CD CD1 CCR1 CCR GSE598 00 <0.0 GSE626 7 1 hasmiR12 12 has-miR-12 hasmiR130a hasmiR130a/b ab 130ab 130a/b hasmiR301a 301ab MS4A GSE59 <0. GSE62 hasmiR1 has-miR-1 hasmiRa GSE5 <0 GSE6 has-miR- < has-miR

Resumo Fundamento O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. Objetivos Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. Métodos Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de |log2fold change| > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Resultados 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. Conclusões Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST. (IAMCSST fatais mundo prognóstico GSE GSE5986 DACE. . (DACE) (GDEs log2fold logfold log fold change 05 0 5 0, 005 0,05 Posteriormente posterior Finalmente GSE6264 75 75% 13 obtidos seguida Cytoscape moleculares disso hasmiR124, hasmiR124 hasmiR has miR 124, 124 has-miR-124 hasmiR130a/b hasmiR130ab hasmiRab 130a/b 130a b hasmiR301a/b hasmiR301ab 301a/b 301a isso EVI1 EVI AML1 AML GATA enriquecidos MS4A3 MSA MS KLRC4 KLRC KLRD1 KLRD AQP CD CD1 CCR1 CCR GSE598 (DACE 00 0,0 GSE626 7 1 hasmiR12 12 has-miR-12 hasmiR130a ab 130ab hasmiR301a 301ab MS4A GSE59 GSE62 hasmiR1 has-miR-1 hasmiRa GSE5 GSE6 has-miR- has-miR