The function and drug development progress of free fatty acid receptor 1 in chronic inflammatory diseases / 药学学报

As a member of G protein coupled-receptors superfamily, free fatty acid receptor 1 (FFAR1), is also known as GPR40, has been shown to regulate numerous pathophysiological processes in a variety of tissues and organs. The activated FFAR1 has a variety of biological functions. For instance, it can not only regulate metabolism of fatty acids and glucose, but also play an important role in immune inflammatory response, it may be a potential drug target for the treatment of various chronic inflammatory diseases. In this review, we focus on the recent researches of FFAR1's action in the regulation of pathophysiological processes, its molecular mechanism and new agonists development. At the same time, this review will take the discovery of series FFAR1 agonists as examples, and display the applied prospects of FFAR1.

Is cutaneous microbiota a player in disease pathogenesis? Comparison of cutaneous microbiota in psoriasis and seborrheic dermatitis with scalp involvement

Background: Knowledge about cutaneous microbiota in psoriasis vulgaris and seborrheic dermatitis is limited, and a comparison of microbiota in the two diseases was not yet previously undertaken. Aims/Objectives: This study aimed to compare the scalp lesional and non-lesional microbiota in psoriasis vulgaris and seborrheic dermatitis with that in a healthy control group. Methods: Fifty samples were taken with sterile swabs from patients’ and controls’ scalps, and 16S rRNA gene sequencing analyses were performed. Results: Alpha and beta diversity analyses showed that bacterial load and diversity were significantly increased in psoriasis vulgaris and seborrheic dermatitis lesions compared to the controls. As phyla, Actinobacteria decreased and Firmicutes increased, while as genera, Propionibacterium decreased; Staphylococcus, Streptococcus, Aquabacterium, Neisseria and Azospirillum increased in lesions of both diseases. Specifically, Mycobacterium, Finegoldia, Haemophilus and Ezakiella increased in psoriasis vulgaris and Enhydrobacter, Micromonospora and Leptotrichia increased in seborrheic dermatitis lesions. Mycobacterium, Ezakiella and Peptoniphilus density were higher in psoriasis vulgaris compared to seborrheic dermatitis lesions. The bacterial diversity and load values of non-lesional scalp in psoriasis vulgaris and seborrheic dermatitis lay between those of lesional areas and controls. Limitations: The small sample size is the main limitation of this study. Conclusion: Higher bacterial diversity was detected in lesions of both psoriasis and seborrheic dermatitis compared to the controls, but similar alterations were observed when the two diseases were compared. Although these differences could be a result rather than a cause of the two diseases, there is a need to analyze all members of the microbiota and microbiota-host interactions

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil

Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Associação do polimorfismo de IL-13 (+1398A/G) com a asma e a ancestralidade genômica / Association of IL-13 (+1398A/G) gene polymorphisms with asthma and genomic ancestry

Introdução: A asma é uma doença complexa, resultante da interação entre fatores genéticos e ambientais. A expressão aumentada de genes relacionados à inflamação define as alterações celulares e estruturais do aparelho respiratório, enquanto o meio ambiente modula os diferentes fenótipos asmáticos. Os produtos dessas células envolvidos na inflamação incluem citocinas, como a interleucina13 (IL-13), que está relacionada com a síntese direta de IgE, imunoglobulina essencial na patogênese da asma. Há divergências entre a prevalência da asma e o grupo étnico estudado, desta forma, o uso de Marcadores Informativos de Ancestralidade (AIM ­ Ancestry Informative Markers) possibilita a caracterização da ancestralidade genômica de diferentes populações. Objetivos: Verificar a associação entre polimorfismos do gene IL-13R com a ancestralidade genômica e a asma em uma população no sul da Bahia. Métodos: Foram genotipadas 320 amostras, sendo 114 casos, e 206 controles, utilizando o método de PCR e PCR/RFLP em sete AIMs (Sb19.3, APO, AT3, RB2300, LPL, CKMM e PV92) que apresentam elevado diferencial de frequência alélica entre africanos, ameríndios e europeu, e um polimorfismo no receptor de IL-13 (IL-13RA1). Resultados: Os resultados desse estudo mostraram que a maior contribuição foi ameríndia, tanto para os casos (37,42%), como para os controles (50,52%), demonstrando que há diferenças nas contribuições étnicas das amostras da região estudada. O polimorfismo no receptor de IL-13 (IL- 13RA1) apresentou associação significativa com rinite e história familiar. Conclusões: A heterogeneidade da composição étnica das amostras pode ter influenciado na não associação das duas variáveis: níveis de IgE sérico e histórico familiar, e a presença do polimorfismo no receptor da IL-13RA1, e aponta a necessidade de realização do controle genômico.

Introduction: Asthma is a complex disease resulting from the interaction between genetic and environmental factors. Increased expression of inflammatory genes defines cellular and structural changes in the respiratory tract, while the environment modulates the different asthmatic phenotypes. Cell products involved in inflammation include cytokines, such as interleukin-13 (IL-13), which is related to the direct synthesis of IgE, an immunoglobulin that plays a key role in the pathogenesis of asthma. Because there is divergence of asthma prevalence between different ethnic groups, the use of ancestry informative markers (AIMs) allows for the characterization of genomic ancestry in different populations. Objectives: To examine the association of IL-13R gene polymorphisms with genomic ancestry and asthma in a population from the south of Bahia. Methods: A total of 320 samples, 114 cases and 206 controls, were genotyped using PCR and PCR/RFLP methods for 7 AIMs (Sb19.3, APO, AT3, RB2300, LPL, CKMM, and PV92) that showed a high allele frequency differential between Africans, Amerindians, and Europeans and 1 polymorphism in the IL-13 receptor (IL-13RA1). Results: Amerindian ancestry provided the greatest contribution in both cases (37.42%) and controls (50.52%), indicating that there are differences in the ethnic contribution of the samples from the study region. The IL-13 receptor (IL-13RA1) polymorphism was significantly associated with rhinitis and family history. Conclusions: Heterogeneity in the ethnic composition of the samples may have influenced the non-association of serum IgE levels and family history with the presence of IL-13RA1 receptor polymorphism, and the results point to the need for genomic control.

Adolescente con síndrome de down y psoriasis severa. veintidos meses de tratamiento con etanercept / Severe psoriasis in a down's syndrome adolescent patient. twenty two months of treatment with etanercept

RESUMEN Reportamos el caso de un paciente de 15 años de edad, con síndrome de Down y psoriasis desde los 2 años. La prevalencia de esta enfermedad en los pacientes con síndrome de Down, varía de 2 al 8% según la literatura consultada. Su cuadro comenzó a muy temprana edad, padeciendo cinco severos cuadros de eritrodermia, que requirieron internación. Durante los últimos 22 meses ha sido tratado con etanercept, reduciendo su PASI de 27 a 2,8 con significativa mejora en su calidad de vida.

SUMMARY We present a 15 years old patient with Down´s syndrome and psoriasis since age 2. Prevalence of psoriasis in patients with Down´s syndrome varies between 2 and 8%. In the case that concerns us, psoriasis started at an early age and suffered five severe erythrodermal events, which required impatient treatment. During the past 22 months the patient has been treated with etanercept, reducing his PASI from 27 to 2.8, hence improving his life quality.

Role of Nucleotide-binding and Oligomerization Domain 2 Protein (NOD2) in the Development of Atherosclerosis

NOD2 (nucleotide-binding and oligomerization domain 2) was initially reported as a susceptibility gene for Crohn's disease, with several studies focused on elucidating its molecular mechanism in the progression of Crohn's disease. We now know that NOD2 is an intracellular bacterial sensing receptor, and that MDP-mediated NOD2 activation drives inflammatory signaling. Various mutations in NOD2 have been reported, with NOD2 loss of function being associated with the development of Crohn's disease and other autoimmune diseases. These results suggest that NOD2 not only has an immune stimulatory function, but also an immune regulatory function. Atherosclerosis is a chronic inflammatory disease of the arterial wall; its pathologic progression is highly dependent on the immune balance. This immune balance is regulated by infiltrating monocytes and macrophages, both of which express NOD2. These findings indicate a potential role of NOD2 in atherosclerosis. The purpose of this review is to outline the known roles of NOD2 signaling in the pathogenesis of atherosclerosis.

Do MEFV mutations influence arterial stiffness in FMF patients.

Background: Pulse wave velocity (PWV) is the most used technique to evaluate the arterial elasticity, which is an early indicator of atherosclerosis. We aimed to evaluate if MEFV Mutations influence arterial stiffness in patients with Familial Mediterranean fever (FMF) Methods: 70 patients diagnosed with FMF and 50 age-and sex-matched controls were included in the study. Genetic analysis of the patients was performed. After the measurement of PWV; the presence of AS was determined. Results: Mean PWV value and arterial stiffness frequency of FMF patients were significantly higher than the control group (p <0.001, p <0.001) respectively. In addition, FMF patients with M694V mutations had higher PWV values and arterial stiffness frequency than those with other mutations. (p=0.045), (p=0.001). There were no differences within all genetic mutation types in terms of arterial stiffness frequency. Conclusions: As a result, due to subclinical inflammation in FMF patients, they have risk for cardiovascular complications. These patients especially those with M694V mutations have to be followed more closely because of increased cardiovascular risk and PWV measurements may be a good tool to detect early development of atherosclerosis.