摘要：
Previous observational studies revealed controversy about the effect of circulating antioxidants on risk of alopecia. In the present study, we investigated the causal relationships between diet-derived circulating antioxidants and 2 non-scarring alopecia using Mendelian randomization (MR). Instrumental variables for antioxidants (lycopene, retinol, ascorbate, beta-carotene, alpha-tocopherol, and gamma-tocopherol) were selected from published studies. Data for alopecia areata (AA) and androgenetic alopecia (AGA) was obtained from the FinnGen study project (R9 released in 2023), including 195 cases and 201,019 controls for AGA and 682 cases and 361,140 controls for AA. We used the inverse variance weighted method as the primary MR method. Three additional methods were used as sensitivity analysis to validate the robustness of the results. We found a causal relationship between absolute beta-carotene levels and AGA risk (P = .039), but not with AA (P = .283). The results of Wald ratio showed a protective effect of absolute beta-carotene levels against AGA, with per 0.1 ln-transformed beta-carotene being associated with a 76% lower risk of AGA (OR: 0.24, 95% CI: 0.06-0.93). Based on the fixed effects inverse variance weighting results, we found that alpha-tocopherol was protective against both AGA (P = .026) and AA (P = .018). For each unit increase in alpha-tocopherol, the effects of change in AGA and AA were 0.02 (95% CI: 0.00-0.61) and 0.10 (95% CI: 0.01-0.67), respectively. The results did not reveal any other causal relationships. Our study identified 3 causal associations of antioxidants with the risk of non-scarring alopecia. These results provide new insights into the prevention of non-scarring alopecia through diet.
摘要：
目的基于酪氨酸激酶/信号传导及转录激活蛋白(Janus kinase/signal transducer and activator of transcription,JAK/STAT)信号通路与免疫缺陷性疾病中CD4<...展开更多 目的基于酪氨酸激酶/信号传导及转录激活蛋白(Janus kinase/signal transducer and activator of transcription,JAK/STAT)信号通路与免疫缺陷性疾病中CD4+T细胞占比减少的相关性,探讨免疫缺陷大鼠CD4+T淋巴细胞分化的机制。方法将SPF级SD大鼠48只,随机分为正常大鼠(24只)和模型大鼠(24只),采用环孢素制备免疫缺陷模型。每组随机选6只验证造模效果,将剩余36只大鼠分为正常组、低鲁组、高鲁组、模型组、模型低鲁组、模型高鲁组,每组6只。低鲁组和模型低鲁组分别注射1.75 mg·kg-1鲁索利替尼,高鲁组和模型高鲁组分别注射3.5 mg·kg-1鲁索利替尼,正常组和模型组注射1.75 mg·kg-1生理盐水,隔日1次,共注射6次。采用流式细胞术检测CD4+T和CD8+T淋巴细胞百分比,计算大鼠脾脏和胸腺指数,HE染色法观察脾脏和胸腺病理改变,ELISA检测白细胞介素-2(interleukin-2,IL-2)、γ-干扰素(interferon-γ,IFN-γ)、白细胞介素-12(interleukin-12,IL-12)、白细胞介素-4(interleukin-4,IL-4)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-10(interleukin-10,IL-10)细胞因子表达量,Western blot检测脾脏组织中酪氨酸激酶2(Janus kinase 2,JAK2)、T盒家族转录因子表达蛋白(T-box family transcription factor expression protein,T-bet)、信号传导及转录激活蛋白4(signal transducer and activator of transcription 4,STAT4)、信号传导及转录激活蛋白6(signal transducer and activator of transcription 6,STAT6)和GATA结合蛋白-3(GATA-binding protein-3,GATA3)蛋白表达量。结果模型组大鼠CD4+T淋巴细胞百分比、胸腺指数较正常组明显下降(P<0.05)。与正常组比较,模型组CD4+T淋巴细胞百分比减少(P<0.05),IL-2、IFN-γ和IL-12表达量下降(P<0.01),IL-10表达量升高(P<0.05);与模型组相比,模型高鲁组CD4+T淋巴细胞百分比、胸腺和脾脏指数、IL-2、IFN-γ显著下降(P<0.05),而GATA3、STAT6蛋白表达量升高(P<0.05),IL-6、IL-10表达量明显增加(P<0.05,P<0.01)。结论免疫缺陷疾病以CD4+T淋巴细胞减少为主要特征,CD4+T细胞亚群失调与JAK/STAT信号通路表达失衡有关,其机制可能与IL-12/STAT4通路表达下调和IL-4/STAT6通路表达上调有关,CD4+T淋巴细胞分化由辅助性T细胞1(helper T cell 1,Th1)向辅助性T细胞2(helper T cell 2,Th2)漂移,造成Th1/Th2失衡,引发免疫缺陷。收起
