Advances in cGAS-STING pathway and its inhibitors in immune and inflammatory diseases / 中国药理学通报

The cGAS-STING signaling pathway is one of the main pathways of immune defense against many types of pathogens. cGAS catalyzes the production of the second messenger cGAMP (cyclic GMP-tVMP) by recognizing plasma DNA and cGAMP subsequently binds to the interferon gene stimulating factor (STING). The pathway induces the production of type I interferon (IFN-I) and activates the innate immune system. The activation of the cGAS-STI]NG pathway could facilitate self-protection,thus STI]NG agonists for tumor immunotherapy have attracted much attention in recent years,and several drug candidates have been in clinical trials. Meanwhile,aberrant activation of cGAS-STI]NG could lead to autoimmune diseases and has attracted extensive interest in developing its inhibitors. This paper summarizes the mechanism and regulatory sites of the cGAS-STI]NG pathway,and outlines the research progress of cGAS-STING pathway-related immune and inflammatory diseases and its inhibitors.

Nosso sistema imune de cada dia e os agrotóxicos de hoje / Our everyday immune system and today's pesticides

O uso massivo dos agrotóxicos nas lavouras deu-se a partir de 1950 com a "Revolução Verde", como resultado da busca por aumento da produtividade e modernização dos campos agrícolas. Diante disso, na década de 1960, foi criado o Programa Nacional de Defensivos Agrícolas (PNDA), que veio para facilitar a introdução dos agroquímicos, colaborando para que, a partir de 2008, o Brasil passasse a ser o país com maiores percentuais de uso destes produtos. Essas substâncias geram efeitos deletérios sobre a resposta imune dos indivíduos expostos, principalmente relacionada aos macrófagos, células B, T e NK. Isso afeta a capacidade de fagocitose, apresentação de antígenos e produção de anticorpos, além de induzir a geração de radicais livres de oxigênio e disfunção mitocondrial, resultando em estresse oxidativo e danos ao DNA celular, apoptose em excesso, mutação no ciclo celular, desordem de regulação e, consequentemente, imunodeficiência. Dessa forma, o desenvolvimento de doenças imunomediadas, como asma e doença pulmonar obstrutiva crônica (DPOC), está estreitamente ligado aos agrotóxicos, uma vez que esses variados mecanismos de toxicidade ao sistema imune induzem, dentre outras, manifestações respiratórias, tais como tosse, sibilo, irritação e inflamação. Além disso, estes pesticidas estão relacionados com doenças não imunomediadas ao alterar a função normal dos hormônios da tireoide, andrógenos e estrógenos. A fim de avaliar estes impactos, o presente estudo consiste em uma revisão integrativa da literatura e, diante da crescente utilização descontrolada dos agrotóxicos, assume grande relevância, refletindo a necessidade de maior atuação da vigilância epidemiológica, ambiental e da saúde do trabalhador.

Beginning in the 1950s, massive pesticide use began in what is called the "Green Revolution", a quest for increased agricultural productivity and modernization. In the 1960s, the Brazilian National Program of Agricultural Defense was created to facilitate the introduction of agrochemicals, leading the country to become one of the world's largest pesticide users by 2008. These substances have deleterious effects on the immune response of exposed individuals, mainly related to macrophages and B, T, and NK cells. This affects phagocytosis and antigen and antibody production, inducing production of oxygen free radicals and mitochondrial dysfunction, which results in oxidative stress and cellular DNA damage, excess apoptosis, cell cycle mutations, regulatory disorders, and, consequently, immunodeficiency. Thus, the development of immune-mediated diseases, such as asthma and chronic obstructive pulmonary disease (COPD), is closely linked to pesticides, since these varied mechanisms of toxicity to the immune system induce respiratory manifestations, such as cough, wheezing, irritation and inflammation. Pesticide use is also related to non-immune-mediated diseases because exposure alters the normal function of thyroid hormones, androgens, and estrogens. To evaluate their impact, the present study performed an integrative review of the literature, which, due to the growing and uncontrolled use of pesticides, is of great relevance and demonstrates the need for greater epidemiological, environmental, and worker health surveillance.

Choices of timing and mode of blood purification in the treatment of immune diseases of nervous system / 中国实用儿科杂志

The immune diseases of nervous system are a kind of nervous system diseases mediated by immune mechanism.High mortality and disability rates are its important characteristics. Early intervention and treatment can significantly improve the clinical outcomes of patients. At present, the main treatments for this kind of diseases include corticosteroid hormone, intravenous immunoglobulin(IVIG)and blood purification. Blood purification therapy has become the focus of current research because of its fast effect and other advantages.The main modes of blood purification therapy for this kind of diseases are plasma exchange and plasma immunoabsorption.Early application of blood purification therapy in patients with the acute attack and critical illness may lead to more significant clinical improvement. Therefore,blood purification may be an effective treatment for patients with the critical illness or when other medications are ineffective for the patients.

Compatibility Rules of Traditional Chinese Medicine in Prevention and Treatment of Scleroderma Based on Data Mining / 世界科学技术-中医药现代化

This study was aimed to analyze compatibility rules of Chinese drugs and prescription design in the pre-vention and treatment of scleroderma. The database of scleroderma treated by Chinese medicine was set up. And then, association rules were used to analyze the prescription compatibility rules. The results showed the highest fre-quency of drugs in the treatment of scleroderma were Astragalus, Angelica sinensis and Salvia. The tonifying and re-plenishing medicinal, blood-activating and stasis-resolving medicinal and exterior-releasing medicinal were with the highest frequency. The commonly used formula in the treatment of scleroderma was Y ang-He decoction. For herbal groups, occurrence of the highest was the combinations of Ramulus Cinnamomi-Astragalus and Carthamus tinctorius L.-Astragalus. Three kinds of herbals were commonly coupled, such as Polygonum multiflorum Thunb. and Caulis Spatholobi with Salvia, P. multiflorum Thunb. and R. Cinnamomi with Salvia, P. multiflorum Thunb. and Astragalus with Salvia, prepared Radix Rehmanniae and Codonopsis with C. tinctorius L., prepared Radix Rehmanniae and Codonopsis with R. Cinnamomi, Codonopsis and Radix paeoniae rubra with R. Cinnamomi. Four kinds of herbals such as R. Cinnamomi, Glycyrrhiza uralensis Fisch., Astragalus and Codonopsis were commonly coupled. It was con-cluded that compatibility rules of Chinese medicine in the prevention and treatment of scleroderma laid the founda-tion for herbal medicine selection and prescription design.

Vascular cognitive impairment in Pemphigus vulgaris: a case report / Comprometimento cognitivo vascular no pênfigo vulgar: relato de caso

Pemphigus vulgaris is a systemic auto-immune medical condition that mainly manifests with changes in skinand vasculopathy. This is a case report of a 69-year-old male with confirmed histopathologic diagnosis of Pemphigus vulgaris presenting ulterior Cognitive Impairment, mostly in executive function. The patient was treated using steroids, immunomodulatory therapy, fluoxetine and galantamine. Neuropsychological testing and magnetic resonance (MRI) were performed. This is the first report of correlational cognitive impairment with Pemphigus vulgaris in the literature. Physicians should be aware of vascular causes for cognitive impairment in patients presenting auto-immune conditions.

Phemphigus vulgaris é uma condição médica sistêmica autoimune que principalmente se manifesta com alterações de pele e vasculopatia. Este é um caso de um homem de 69 anos com diagnóstico histopatológico de Phemphigus vulgaris apresentando posterior comprometimento cognitivo, predominante em funções executivas. O paciente foi tratado com esteroides, terapia imunomoduladora, fluoxetina e galantamina. Avaliação neuropsicológica e ressonância magnética foram realizados. Este é o primeiro relato correlacionando comprometimento cognitivo a pênfigo vulgar na literatura. Os clínicos devem estar cientes das causas vasculares para comprometimento cognitivo em pacientes se apresentando comcondições autoimunes.

Health related quality of life of chronic patients with immune system diseases: a pilot study / Qualidade de vida relacionada com a saúde de doentes crónicos com patologias do sistema imune: estudo piloto / Calidad de vida relacionada con la salud de pacientes crónicos con enfermedades del sistema inmune: estudio piloto

Health related quality of life (HRQL) and survival are two important outcome measures in chronic diseases. This study aimed to compared HRQL in patients with different chronic diseases of immune system and normative data from the general Portuguese Population. It was selected 103 out-patients, by convenience, to complete SF-36v2. The lowest scores were found among measures for general health (41.0), vitality (47.5), bodily pain (51.0), mental health (56.4); women, except for role-physical, and patients with auto-immune diseases have had the worse scores on all assessed dimension of subjective health, when compared with normative data. Highest scores were obtained in the following scales: physical functioning (69.1), social functioning (66.9), role-emotional (64.9). Living with chronic immune disease have impact on HRQL and it can be expected that the Portuguese version of SF-36v2 provide valid and reliable HRQL data.

A qualidade de vida relacionada com a saúde (QVRS) e sobrevivência são dois desfechos importantes nas doenças crónicas. Este estudo objetivou comparar a QVRS de pacientes com diferentes patologias crónicas do sistema imune e com os dados normativos da população Portuguesa. Foram seleccionados 103 pacientes para a amostra por conveniência, para completar o SF-32v2. As pontuações mais baixas foram encontradas entre as medidas para a saúde geral (41,0), vitalidade (47,5), dor (51,0) e saúde mental (56,4); as mulheres, exceto na função física, e os doentes com doenças autoimunes obtiveram piores escores em todas as dimensões, quando comparados com os dados normativos. Os escores mais altos foram obtidos nas dimensões: função física (69,1), funcionamento social (66,9) e função emocional (64,9). Viver com doenças crónicas imunológicas apresenta impacto sobre a QVRS e a versão Portuguesa do SF-36v2 fornece dados válidos e confiáveis na mensuração da QdV destes doentes.

Calidad de vida relacionada con la salud (CVRS) y la supervivencia son dos resultados importantes en las enfermedades crónicas. El objetivo de este estudio fue comparar la calidad de vida relacionada con la salud (CVRS) de los pacientes con diferentes patologías del sistema inmunológico y los datos normativos de la población portuguesa. 103 pacientes fueron seleccionados al acaso para completar el cuestionario SF-32v2. Las más bajas mensuras se encuentran entre las medidas de salud en general (41,0), vitalidad (47,5), dolor (51,0) y salud mental (56,4) que las mujeres en la función física y los pacientes con enfermedades autoinmunes también obtuvieron peores puntuaciones, en todas las dimensiones en comparación con los datos normativos. Las puntuaciones más altas se obtuvieron en las dimensiones: función física (69,1), funcionamiento social (66,9), función emocional (64,9). Vivir con enfermedades crónicas inmunológicas ten un impacto en la CVRS y la versión portuguesa del cuestionario SF 36v2 aporta datos válidos y confiables para medir la CdV de estos pacientes.

Prevalência de prolapso de valva mitral e doença tireoidiana em pacientes com artrite reumatóide de um hospital universitário / Mitral valve prolapse and thyroid diseases in patients with rheuma-toid arthritis in a university hospital

A correlação entre doença auto-imune tireoidiana e artrite reumatóide tem sido demonstrada de longa data. A incidência de prolapso de valva mitral é maior em populações com doença tireoidiana. Acredita-se haver algum componente auto-imune relacionado ao prolapso de valva mitral. Nesse estudo foram avaliados 203 prontuários de pacientes com Artrite reumatóide com ecocardiograma com o objetivo de estabelecer a prevalência de prolapso de valva mitral e doença tireoidiana nessa população. Desses 19 (9,3%) eram homens e 184 (90,6%) eram mulheres. A idade média foi de 53,50±13.67 anos) e o tempo médio de doença de 102±105.8 meses. O prolapso de valva mitral foi visto em 18 (8,86%) pacientes. A avaliação da função tireoidiana foi realizada em 186 indivíduos e desses 3 (1,6%) tinham hipertireoidismo, 28 (15,05%) hipotireoidismo e 155 (83,33%) eram eutireoideos. Pacientes com prolapso de válvula mitral não diferenciaram dos sem prolapso quanto à presença do látex (p=0,5), titulo do látex (p=0,51), presença de FAN (p=0,76), presença de hipotireoidismo (p=0,47), sexo (p=1,0) e idade de aparecimento da doença (p=0,1). Pacientes com prolapso de válvula mitral tinham artrite reumatóide de maior duração (p=0,0021). Conclusão: Os pacientes de artrite reumatóide com prolapso de valva mitral não se diferenciam da população sem prolapso quanto a sexo, idade de início da artrite reumatóide, presença e titulo do fator reumatóide, presença de FAN e de hipotireoidismo.

There is a well established correlation between auto-immune thyroid diseases and rheuma-toid arthritis. The mitral valve prolapse incidence is higher among the patients with thyroid diseases and it´s believed that there is an auto-immune component in its origins. The objective of this study was to explore the prevalence of mitral valve prolapse and thyroid disease in 203 patients with rheumatoid arthritis. The results showed that 19 (9, 3%) were men and 184 (90,6%) were women. The average age was 53, 50±13.67 years and the average time of disease was 102±105.8 months. The mitral valve prolapse prevalence was 8, 86% (18 pa-tients). The thyroid function was studied in 186 patients. Among these, 3 (1, 6%) had hyperthyroidism, 28 (15, 05%) hypothyroidism and in 155 (83, 33%) the thyroid function were normal. There was no difference between individuals with mitral valve prolapse and without on rheumatoid factor presence (p=0,5), latex title (p=0,51), antinuclear antibody presence (p=0,76), hipothyroidism (p=0,47), gender (p=1,0) and age of rheumatoid arthritis onset (p=0,1). Patients with mitral valve prolapse had longer disease duration (p=0,0021). Conclusion: The rheumatoid arthritis patients with mitral valve prolapse from this study have no significant differences from the population without mitral valve prolapse in gender, age of disease onset, presence and levels of rheumatoid factor, presence of antinuclear anti-bodies and hypothyroidism.

Role of chemokine receptor CXCR3 in immune diseases / 第二军医大学学报

The roles of chemokine and chemokine receptor family in immune diseases are drawing increasing attention, as they are very important in maintaining cell survival, inducing gene expression, directly guiding cell migration and regulating immunity. The paper reviews the expression and possible roles of chemokine receptor CXCR3 and its ligands in immune diseases, as well as the latest therapies targeting them.

Approach to diagnosis of auto-immune hepatitis.

Auto-immune hepatitis (AIH) is one of the chronic liver diseases, seen predominantly in women, resulting from dysregulated immune mechanisms not yet clearly defined. Based on a combination of clinical and laboratory parameters with both positive and negative weights, the International AIH Group devised a scoring system in 1993. The system was modified in 1999 and has proven useful for both diagnostic and research purposes. This review deliberates on the clinical, immunological and histological features of this entity.