Systemic lupus erythematosus and Atopic dermatitis: A two sample Mendelian randomization study.

BACKGROUND: Systemic lupus erythematosus (SLE) and atopic dermatitis (AD) are common diseases in human populations. Previous studies have suggested a potential association between SLE and AD. However, the causal relationship and direction between the two conditions remain unclear. OBJECTIVE: The aim of this study is to evaluate the causal relationship between SLE and AD. METHODS: In this study, we employed Mendelian randomization (MR) analysis to investigate the causal relationship between SLE and AD. MR analysis has the advantage of reducing confounding factors, determining the direction of causality, and providing quantitative effect estimates. We obtained summary data from genome-wide association studies (GWAS) on SLE and AD from publicly available databases. Five MR methods, namely MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode, were used to assess the causal relationship between SLE and AD. Several techniques, including MR-Egger intercept, MR-PRESSO, and Cochran's Q test, were utilized to evaluate heterogeneity and pleiotropy. RESULTS: Our study demonstrated a causal relationship between the prevalence of SLE and an increased risk of AD (MR Egger OR: 1.567, 95% CI: [1.041, 1.285], P = 0.009; IVW OR: 1.085, 95% CI: [1.005, 1.143], P = 0.035). Furthermore, sensitivity analyses did not detect heterogeneity or pleiotropy. CONCLUSION: Our research finds that SLE is a contributing factor to the development of AD, providing valuable insights into the pathogenesis and prevention of both diseases. Key Points • Currently, there is no research that clearly indicates a causal relationship between SLE and AD. This study, for the first time, identified a positive causal relationship between SLE and AD. • The results of this study contribute to our understanding of the pathogenesis and treatment strategies for SLE and AD, providing some guidance for future clinical practice.

Current Advances in Naturally Occurring Caffeoylquinic Acids: Structure, Bioactivity, and Synthesis.

Caffeoylquinic acids (CQAs) are a broad class of secondary metabolites that have been found in edible and medicinal plants from various families. It has been 100 years since the discovery of chlorogenic acid in 1920. In recent years, a number of naturally derived CQAs have been isolated and structurally elucidated. Accumulated evidence demonstrate that CQAs have a wide range of biological activities, such as antioxidation, antibacterial, antiparasitic, neuroprotective, anti-inflammatory, anticancer, antiviral, and antidiabetic effects. Up to date, some meaningful progresses on the biosynthesis and total synthesis of CQAs have also been made. Therefore, it is necessary to comprehensively summarize the structure, biological activity, biosynthesis, and chemical synthesis of CQAs. This review provides extensive coverage of naturally occurring CQAs discovered from 1990 until 2020. Modern isolation techniques, chemical data (including structure, biosynthesis, and total synthesis), and bioactivity are summarized. This would be helpful for further research of CQAs as potential pharmaceutical agents.

A comprehensive description of GluN2B-selective N-methyl-D-aspartate (NMDA) receptor antagonists.

l-glutamate is an excitatory neurotransmitter in the central nervous system (CNS), which can activate ionotropic receptors (iGluRs) and metabotropic (mGluRs) receptors. N-methyl-D-aspartate (NMDA) receptor is a ligand-gated ion channel belonging to the iGluRs family. Among NMDA receptor subtypes, GluN2B subtype plays a crucial role in CNS diseases. In this review, we summarize, classify and discuss the reports on GluN2B antagonists, published from the 1990s to 2020, to provide the therapeutic potential of GluN2B antagonists on various disorders. The GluN2B antagonists are broadly classified into two categories, which are prototypical antagonists and atypical antagonists. And the latter are further divided into amidine derivatives, 4-aminoquinolines, indole derivatives, benzimidazole derivatives, oxamide derivatives, carbamate derivatives, EVT-101 analogues, 1H-pyrrolo[3,2-b]pyridine derivatives, benzazepin derivatives, other heterocyles and radiotracers. This review will provide a comprehensive description including structure, structure-activity relationship (SAR), and pharmacology of novel GluN2B-subtype selective NMDA antagonists to the medicinal chemists, which would be helpful in rational designing effective drugs aimed toward related CNS disease.

Jiang Gui Fang activated interscapular brown adipose tissue and induced epididymal white adipose tissue browning through the PPARγ/SIRT1-PGC1α pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Gui Zhi Tang, a well-known Chinese herbal formula recorded in the Eastern Han Dynasty, has been widely used to treat exogenous cold for thousands of years. Recent studies have shown that Gui Zhi Tang has the effect of regulating the body temperature. Because of its effect on heat production, protecting vital organs of the body and avoiding damage from the cold environment, Jiang Gui Fang (JG) was obtained from the Department of Traditional Chinese Medicine at the General Hospital of Northern Theatre Command where it has been used clinically for many years and has exhibited favourable efficacy. Based on research on Gui Zhi Tang, the principles of traditional Chinese medicine and survey of a large number of studies, this empirical formula was developed. The composition of JG included Dried ginger, Cassia twig, and Liquorice in Gui Zhi Tang, which play a major role in the treatment of exogenous cold, and combined these components with other Chinese medicines, such as Pueraria, Spatholobus, Acanthopanacis cortex, Evodiae fructus, and Codonopsis pilosula. AIM OF THE STUDY: To promote the core body temperature and prevent invasion of the major organs from the cold environment, we studied the effect of JG on the core body temperature of mice and then explored its regulation of interscapular brown adipose tissue (iBAT) and epididymal white adipose tissue (eWAT) and the possible mechanism. Finally, we determined the phytochemical composition of JG that plays a role in heat production. MATERIALS AND METHODS: In vivo study, we performed a 4-week treatment of JG in acute cold environment at -20 °C and chronic cold exposure at 4 °C. The core temperature, adipose tissue weight, serum parameters, and morphological observation of adipocytes, liver and kidney were measured. Then we investigated the expression levels of adipogenic factors, thermogenic factors and lipoprotein. In vitro, we determined the lipid droplet content, ATP content, and the maximum oxygen consumption of mitochondria. RESULTS: JG treatment promoted core temperature, inhibited eWAT weight, protected liver, and reduced glucose and lipids in Kunming (KM) mice. JG also increased the expression of BAT-associated thermogenic factors, including uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α). The levels of the lipogenic factor peroxisome proliferate-activator receptor gamma (PPARγ) and the lipolytic protein hormone-sensitive triglyceride lipase (HSL) in eWAT were elevated. The results of H&E and immunohistochemistry showed that JG significantly reduced the size of iBAT and eWAT and increased the content of UCP1. In vitro, JG reduced the content of lipid droplets and ATP in brown fat cells. The maximum oxygen consumption capacity of mitochondria and the expression levels of UCP1, PGC1α and silent mating type information regulation 2 homologue 1 (SIRT1) were enhanced after JG treatment. CONCLUSIONS: In vivo and in vitro studies, the results demonstrated that JG obviously increased the core temperature of mice by activating iBAT and inducing eWAT browning, which proved the mechanism is closely related to the PPARγ/SIRT1- PGC1α pathway. In this paper, we will provide a reference for further study of iBAT activation and eWAT browning.

Novel ADAM-17 inhibitor ZLDI-8 inhibits the proliferation and metastasis of chemo-resistant non-small-cell lung cancer by reversing Notch and epithelial mesenchymal transition in vitro and in vivo.

Acquired drug-resistant non-small cell lung cancer (NSCLC) has strong proliferation ability and is prone to epithelial-mesenchymal transition (EMT) and subsequent metastasis. Notch pathway mediates cell survival and EMT and is involved in the induction of multidrug resistance (MDR). ZLDI-8 is an inhibitor of Notch activating/cleaving enzyme ADAM-17 we found before. However, the effects of ZLDI-8 on resistant NSCLC was unclear. Here, we demonstrated for the first time that ZLDI-8 could induce apoptosis in lung cancer, especially in chemotherapy-resistant non-small cell lung cancer cells, and also inhibit migration, invasion and EMT phenotype of drug-resistant lung cancer. ZLDI-8 inhibits the Notch signaling pathway, thereby regulating the expression of survival/apoptosis and EMT-related proteins. Moreover, ZLDI-8 suppresses multidrug-resistant lung cancer xenograft growth in vivo and blocks metastasis in a tail vein injection mice model. Therefore, ZLDI-8 is expected to be an effective agent in the treatment of drug-resistant lung cancer.