Association of atopic dermatitis with autoimmune diseases: A bidirectional and multivariable two-sample mendelian randomization study

BackgroundObservational studies have suggested the association between atopic dermatitis (AD) and the risks of autoimmune diseases. It is still unclear, however, whether or in which direction causal relationships exist, because these associations could be confounded.ObjectivesOur study seeks to assess the possibility of AD as a cause of autoimmune diseases, and to estimate the magnitude of the causal effect.MethodsTwo-sample mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) summary-level statistics. Specifically, bidirectional MR analyses were conducted to examine the direction of association of AD with autoimmune diseases; multivariable MR analyses (MVMR1) were used to test the independence of causal association of AD with autoimmune diseases after controlling other atopic disorders (asthma and allergic rhinitis), while MVMR2 analyses were conducted to account for potential confounding factors such as smoking, drinking, and obesity. Genetic instruments for AD (Ncases=22 474) were from the latest GWAS meta-analysis. The GWAS summary data for asthma and allergic rhinitis were obtained from UK Biobank. The GWAS summary data for smoking, alcohol consumption, obesity and autoimmune diseases (alopecia areata, vitiligo, systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, and type 1 diabetes) were selected from the largest GWASs available. Causal estimates were derived by the inverse-variance weighted method and verified through a series of sensitivity analyses.ResultsGenetically predicted AD linked to higher risks of rheumatoid arthritis (OR, 1.28; P=0.0068) (ORMVMR1, 1.65; P=0.0020) (ORMVMR2, 1.36; P<0.001), type 1 diabetes (OR, 1.37; P=0.0084) (ORMVMR1, 1.42; P=0.0155) (ORMVMR2, 1.45; P=0.002), and alopecia areata (OR, 1.98; P=0.0059) (ORMVMR1, 2.55; P<0.001) (ORMVMR2, 1.99; P=0.003) in both univariable and multivariable MR. These causal relationships were supported by sensitivity analyses. No causal effect of AD was identified in relation to systemic lupus erythematosus, vitiligo, and ankylosing spondylitis. Concerning the reverse directions, no significant association was noted.ConclusionThe results of this MR study provide evidence to support the idea that AD causes a greater risk of rheumatoid arthritis, type 1 diabetes and alopecia areata. Further replication in larger samples is needed to validate our findings, and experimental studies are needed to explore the underlying mechanisms of these causal effects

A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi

In this study, the effect of four xyloketal compounds 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal compound with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals were easily penetrable through the cell membrane. Moreover, the molecular docking study of xyloketal A with activation region of the stromal interaction molecule (STIM) 1 and the calcium release-activated calcium modulator (ORAI) 1 (STIM1-ORAI1) protein complex, the key domain of SOCE, revealed that xyloketal A exibited non-covalent interaction with the key residue lysine 363 (LYS363) in the identified cytosolic regions in STIM1-C. These findings provided useful information for xyloketal A as SOCE inhibitor for further evaluation

Age- and Gender-Specific Prevalence of Risk Factors in Patients with First-Ever Ischemic Stroke in China

Background. Evidences are accumulating that age and gender have great impact on the distribution of stroke risk factors. Such data are lacking in Chinese population. Methods. 1027 patients with first-ever ischemic stroke (IS) were recruited and divided into young adult (<50 years), middle-aged (50∼80 years), and very old (>80 years) groups according to stroke onset ages. Vascular risk factors were collected and compared among groups. Results. Female patients were globally older than male patients at stroke onset and having higher prevalence of diabetes mellitus (DM), heart diseases, and atrial fibrillation (AF). However, females were less likely to drink heavily or smoke than males. Young patients had a much higher proportion of smoking and drinking than middle-aged and very old patients and the highest family history of hypertension, while very old patients had the highest prevalence of heart diseases and AF but lowest proportion of positive family history of vascular diseases. Hypertension and DM were equally frequent among three groups. Conclusion. Our study showed that vascular risk factors had a specific age and gender distribution pattern in Chinese IS patients. Secondary prevention strategy should emphasize on the control of different risk factors based on patient's age and gender

Correction : Radtke et al. Plasma Treatments and Light Extraction from Fluorinated CVD-Grown (400) Single Crystal Diamond Nanopillars. C 2020, 6, 37

The authors would like to update the XPS spectrum in Figure 3c [...