Abstract Background The etiology of systemic lupus erythematosus is complex and incurable. A large number of systematic reviews have studied the risk factors of it. Mendelian randomization is an analytical method that uses genetic data as tool variables to evaluate the causal relationship between exposure and outcome. Objective To review the systematic reviews and Mendelian randomization studies that focused on the risk factors of systemic lupus erythematosus and shed light on the development of treatments for its prevention and intervention. Methods From inception to January 2022, we systematically searched MEDLINE (via PubMed) and Embase for related systematic reviews and Mendelian randomization studies. Extract relevant main data for studies that meet inclusion criteria. The quality of systematic reviews was assessed by using Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Finally, the risk factors are scored comprehensively according to the results' quantity, quality, and consistency. Results Our study involved 64 systematic reviews and 12 Mendelian randomization studies. The results of systematic reviews showed that diseases (endometriosis, atopic dermatitis, allergic rhinitis), lifestyle (smoking, drinking, vaccination), and gene polymorphism influenced the incidence of systemic lupus erythematosus. The results of Mendelian randomization studies identified the role of disease (periodontitis, celiac disease), trace elements (selenium, iron), cytokines (growth differentiation factor 15), and gut microbiome in the pathogenesis of systemic lupus erythematosus. Conclusion We should pay attention to preventing and treating systemic lupus erythematosus in patients with endometriosis, celiac disease, and periodontitis. Take appropriate dietary supplements to increase serum iron and selenium levels to reduce the risk of systemic lupus erythematosus. There should be no excessive intervention in lifestyles such as smoking and drinking.

RESUMO Antecedentes: A acupuntura é um tratamento para a dor neuropática, mas seu mecanismo permanece obscuro. Estudos anteriores mostraram que a analgesia foi induzida em ratos com dor neuropática quando o conteúdo de adenosina da medula espinhal aumentou após a eletroacupuntura (EA); no entanto, o mecanismo por trás desse aumento induzido por eletroacupuntura não foi esclarecido. Objetivo: Este estudo teve como objetivo determinar o papel que a ecto-5'-nucleotidase desempenha na analgesia induzida por EA para dor neuropática. Métodos: Realizamos eletroacupuntura no ponto de acupuntura de Zusanli no sétimo dia após estabelecer um modelo de rato de dor neuropática induzida por lesão de constrição crônica. Observamos o limiar de retirada mecânica e o limiar de dor térmica, e detectamos a expressão de ecto-5'-nucleotidase na medula espinhal usando Western blot. Modelos de ratos com lesão de constrição crônica foram injetados intraperitonealmente com α, β-metilenadenosina 5'-difosfato, um inibidor de ecto-5'-nucleotidase, 30 min antes da eletroacupuntura. O conteúdo de adenosina da medula espinhal foi detectado por meio de cromatografia líquida de alta eficiência. Por último, o agonista do receptor de adenosina A1 N6-ciclopentiladenosina foi injetado por via intratecal no edema lombar dos ratos, e a retirada mecânica e os limiares de dor térmica foram reavaliados. Resultados: Analgesia e aumento da expressão de ecto-5'-nucleotidase e conteúdo de adenosina na medula espinhal foram observados 1 h após a eletroacupuntura. α, β-metilenadenosina 5'-difosfato foi capaz de inibir a sobrerregulação do conteúdo de adenosina e analgesia induzida por eletroacupuntura. Após administração de N6-ciclopentiladenosina, a analgesia induzida por eletroacupuntura foi restaurada. Conclusões: Nossos resultados sugerem que a eletroacupuntura em Zusanli pode produzir analgesia em modelos de ratos com lesão de constrição crônica, possivelmente por meio do aumento da expressão de ecto-5'-nucleotidase induzida por eletroacupuntura, levando ao aumento da expressão de adenosina na medula espinhal.

ABSTRACT Background: Acupuncture is a treatment for neuropathic pain, but its mechanism remains unclear. Previous studies showed that analgesia was induced in rats with neuropathic pain when their spinal cord adenosine content increased after electroacupuncture (EA); however, the mechanism behind this electroacupuncture-induced increase has not been clarified. Objective: This study aimed to determine the role that ecto-5’-nucleotidase plays in EA-induced analgesia for neuropathic pain. Methods: We performed electroacupuncture at the Zusanli acupoint on the seventh day after establishing a rat model of neuropathic pain induced through chronic constriction injuries. We observed the mechanical withdrawal threshold and thermal pain threshold and detected the expression of ecto-5’-nucleotidase in the spinal cord using Western blot. Chronic constriction injury rat models were intraperitoneally injected with α,β-methyleneadenosine 5'-diphosphate, an ecto-5’-nucleotidase inhibitor, 30 min before electroacupuncture. The adenosine content of the spinal cord was detected using high-performance liquid chromatography. Lastly, the adenosine A1 receptor agonist N6-cyclopentyladenosine was intrathecally injected into the lumbar swelling of the rats, and the mechanical withdrawal and thermal pain thresholds were reevaluated. Results: Analgesia and increased ecto-5’-nucleotidase expression and adenosine content in the spinal cord were observed 1 h after electroacupuncture. α,β-methyleneadenosine 5'-diphosphate was able to inhibit upregulation of adenosine content and electroacupuncture-induced analgesia. After administration of N6-cyclopentyladenosine, electroacupuncture-induced analgesia was restored. Conclusions: Our results suggest that electroacupuncture at Zusanli can produce analgesia in chronic constriction injury rat models, possibly via the increased ecto-5’-nucleotidase expression induced through electroacupuncture, thus leading to increased adenosine expression in the spinal cord.

Abstract The aim of this study was to evaluate the impact and mechanism of co-blocking of costimulatory signals CD28-B7-CD40-CD40L during immune allograft rejection. Forty-eight recipient rabbits were prepared as a high-risk corneal allograft model. After surgery, the animals were randomly divided into: control group, MR1 group, anti-B7 group, and co-blocking group (n=12, each group). Subconjunctival injection was first performed on the allograft surgery day until post-surgery day five. Four weeks later, or when immune rejection occurred, the cornea was sampled to detect and analyze the gene spectrum. The survival time in the co-blocking group was significantly longer than that in the other three groups (p < 0.05). Gene expression analysis revealed that the expression of genes associated with immune rejection, interleukin (IL)-1α, IL-1β, intercellular cell adhesion molecule-1, and IL-2 was down-regulated in the co-blocking group, while IL-10 was up-regulated, but the changes in nuclear factor-κB and interferon-γ were not significant. In conclusion, the co-blocking of costimulatory signals can significantly reduce genes that promote corneal allograft rejection. The inhibition of corneal allograft rejection gene expression was significantly enhanced. These gene expression results can explain the conclusion of previous work at the genetic level.

Abstract Two new monoterpene glycosides, perillanolides A and B, together with a known compound reported from the genus Perilla for the first time were isolated and characterized from the leaves of Perilla frutescens (L.) Britton, Lamiaceae, a garnish and colorant for foods as well as commonly used for traditional medicine. The structures of the isolated compounds were elucidated on the basis of extensive spectroscopic evidences derived from nuclear magnetic resonance experiments, mass spectrometry and by comparing their physical and spectroscopic data of literature. These compounds, together with the previously isolated secondary metabolites of this species, were investigated for their inhibitory effects on xanthine oxidase in vitro. Of the compounds, luteolin showed the strongest inhibitory activity with an IC50 value of 2.18 µM. Esculetin and scutellarein moderately inhibited the enzyme, while perillanolides A and B, and 4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-β-D-glucopyranoside exerted weak activities.