ABSTRACT
Background: Traditional observational studies have found a possible risk association of the gut microbiota for psoriasis. Meanwhile, psoriasis may also affect the changes in the gut microbiota. However, the available evidence does not demonstrate a reciprocal relationship between the gut microbiota and psoriasis. This limits our understanding on the role of the gut microbiota in the mechanisms of psoriasis. Methods: To address this question we used Mendelian randomization, a novel epidemiological approach, and acquired the largest current gut microbiota GWAS data from the MiBioGen consortium as well as psoriasis GWAS data from the FinnGen consortium, and performed two-sample bidirectional MR analyses using a multiple MR analysis approach. Finally, the robustness of the results was assessed by sensitivity analysis. Results: Our results indicate that five bacterial genera are causally related to psoriasis and psoriasis is causally related to four bacterial genera. Conclusion: These results suggest a bidirectional causal influence of psoriasis on the gut microbiota. Our results somewhat challenge the causal inferences of previous observational studies. We found that the specific bacterial genera with a risk effect on psoriasis were different from those found to characterize psoriasis in previous observational studies, and that these psoriasis-characterizing genera were inversely associated with psoriasis.
ABSTRACT
Psoriasis is an immune-mediated chronic inflammatory disease that can be combined with complications such as diabetes, cardiovascular disease, obesity, and kidney disease. The comorbidity of psoriasis with autoimmune bullous diseases (AIBD) has been reported previously in several cases, the most frequent of which is bullous pemphigoid (BP). The underlying mechanisms of psoriasis with BP are not clear and there are no uniform treatment criteria. Based on previous case reports, the coexistence of psoriasis and BP may be related to inflammatory activity, medications, phototherapy, and infection. We report a case of a psoriasis patient who developed BP after taking Chinese herbal compounds and was successfully treated with dupilumab, which is the first reported case of applying dupilumab to treat psoriasis with BP comorbidities.
ABSTRACT
BACKGROUND: Fibroblast growth factor 21 (FGF21), an FGF family member, is an atypical hormone and pro-longevity factor. METHODS: To better understand of the effects of exogenous administration of FGF21 on lifespan and stress tolerance, and the underlying molecular basis, we used the silkworm, Bombyx mori, as an experimental animal model to evaluate FGF21's pharmaceutical effects. RESULTS: Lifespan was significantly prolonged in female silkworms with FGF21 replenishment, whereas no effect was observed in the male silkworms. FGF21 replenishment also significantly improved the activity of antioxidant systems such as glutathione-S-transferase (GST) and superoxide dismutase (SOD) and significantly decreased malondialdehyde (MDA) content. Moreover, FGF21 was found to play a critical role in enhancing stress resistance, including ultraviolet (UV) irradiation tolerance and thermotolerance. Furthermore, AMPK, FoxO, and sirtuins were activated by FGF21 and may be responsible for the prolonged lifespan and enhanced antioxidant activity observed in silkworms. CONCLUSIONS: Collectively, the results suggest the molecular pathways underlying of FGF21-induced longevity and stress tolerance, and support the use of silkworms as a promising experimental animal model for evaluating the pharmaceutical effects of small molecules.
