The potential causal relationship between various lifestyles and depression: a univariable and multivariable Mendelian randomization study.

Background: Previous studies have shown that lifestyle was associated with depression. Thus, the aim of this study was to examine the causality between multiple lifestyles and depression by Mendelian randomization (MR) analysis. Methods: The single-nucleotide polymorphisms (SNPs) of depression, alcoholic drinks per week, sleeplessness or insomnia, body mass index (BMI), mood swings, weekly usage of mobile phone in the last 3 months, beef intake, cooked vegetable intake, and "smoking status: never" were acquired from the Integrative Epidemiology Unit Open genome-wide association study database. Causal effects of eight exposure factors and depression were investigated using MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode, and results were primarily referred to IVW. Subsequently, univariable MR (UVMR) analysis was performed on eight exposure factors and depression, separately. In addition, sensitivity analysis, including heterogeneity test, horizontal pleiotropy, and leave-one-out (LOO) methods, was conducted to evaluate the stability of MR results. Furthermore, multivariable MR (MVMR) analysis was carried out. Results: UVMR analysis revealed that all eight exposure factors were causally associated with depression; alcoholic drinks per week, sleeplessness or insomnia, BMI, mood swings, weekly usage of mobile phone in the last 3 months, and cooked vegetable intake were risk factors, and beef intake and "smoking status: never" were protection factors. Heterogeneity tests revealed no heterogeneity for alcoholic drinks per week, sleeplessness or insomnia, mood swings, weekly usage of mobile phone in the last 3 months, and cooked vegetable intake. Meanwhile, there was no horizontal pleiotropy in UVMR, and LOO analysis verified that univariable analysis results were reliable. Moreover, MVMR analysis indicated that mood swings and weekly usage of mobile phone in the last 3 months were risk factors, and beef intake was a protection factor for depression when multiple factors occurred at the same time. Conclusion: Alcoholic drinks per week, sleeplessness or insomnia, BMI, mood swings, weekly usage of mobile phone in the last 3 months, and cooked vegetable intake were risk factors, and beef intake and "smoking status: never" were protection factors. In addition, mood swings, weekly usage of mobile phone in the last 3 months, and beef intake had a direct effect on depression when multiple factors occurred simultaneously.

Diterpenoids with Schistosomula-Killing and Anti-Fibrosis Activities In Vitro from the Leaves of Croton tiglium.

The leaves of C. tiglium have been comprehensively researched for their structurally novel bioactive natural compounds, especially those with anti-schistosomiasis liver fibrosis activity, because ethyl acetate extract, which can be extracted from the leaves of C. tiglium, has good anti-schistosomiasis liver fibrosis effects. One new tigliane-type diterpene, 20-acetyl-13-O-(2-metyl)butyryl-phorbol (1), and nine known (2-10) analogues were isolated from the leaves of C. tiglium. Their structures were elucidated on the basis of spectroscopic analysis and ECD analysis. All diterpenoids had a stronger insecticidal effect on schistosomula, and compounds 2, 4, and 10 had good anti-liver-fibrosis effects. Furthermore, compared with the model group, compound 2 significantly downregulated the protein and mRNA expression of COL-I, COL-III, α-SMA, and TGF-ß1 on TGF-ß1-induced liver fibrosis in LX-2 cells. Meanwhile, compound 2 also regulated the expression of TGF-ß/Smad-pathway-related proteins. The results suggest that diterpenoids from C. tiglium may serve as potential schistosomula-killing and anti-liver-fibrosis agents in the future.

Crotonols A and B, two rare tigliane diterpenoid derivatives against K562 cells from Croton tiglium.

Crotonols A and B (1 and 2), two tigliane diterpenoids featuring a rare C-7/C-14 cyclized and novel 5/7/7-fused carbon skeleton, along with the known tigliane wallichiioid A, were isolated from the leaves of Croton tiglium. Their structures were determined through spectroscopic methods, X-ray crystallography and ECD analysis. To the best of our knowledge, crotonol B (2) represents the first example of 13,14-seco-tigliane diterpenoids. Crotonols A and B displayed strong cytotoxic activities against the K562 cell line with IC50 values of 0.20 and 0.21 µM, respectively. Furthermore, crotonol A promoted the apoptosis of K562 cells through the cleavage of PARP and the accumulation of bax as well as the degradation of bcl-2.

Antitubercular and cytotoxic tigliane-type diterpenoids from Croton tiglium.

Five new tigliane diterpene esters (1-5), highly oxygenated tetracyclic diterpenoid carbon skeleton, together with three known analogues (6-8) were isolated from the leaves of Croton tiglium. Extensive NMR and mass spectroscopic analysis were used to elucidate their structures. Most of the isolated compounds were tested for their cytotoxic and antitubercular activities. Among them, the cytotoxic activities of these tigliane-type diterpenes strongly depend on the species of the tumor cells. Especially, these bioactivity compounds showed strong cytotoxic activities against the K562 cell line, and their inhibition effects were close to the positive control Taxol. Furthermore, compounds 1, 2, 6, and 7 showed potent antitubercular activities with MIC values of 19.5, 20.9, 20.5, and 13.4µM, respectively.

Dicarabrol, a new dimeric sesquiterpene from Carpesium abrotanoides L.

A new dimeric sesquiterpene, dicarabrol (1), together with three known sesquiterpenes, carabrol (2), 11(13)-dehydroivaxillin (3), and 2-desoxy-4-epi-pulchellin (4), were isolated from the whole plant of Carpesium abrotanoides L. Their structures were elucidated on the basis of spectroscopic analysis, and single crystal X-ray diffraction analysis. Compound 1 possessed a dimeric sesquiterpene core featured with a cyclopentane ring connecting two sesquiterpene lactone units rarely discovered in nature. Dicarabrol (1), as well as three known sesquiterpenes (2-4), had potent in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U937, H1975, SGC-7901, A549, MOLT-4, and HL60 cell lines with IC50 values ranging from 0.10 to 46.7 µM, while they showed significant antiviral (H1N1 and H3N2) activities. Furthermore, compounds 1, 3 and 4 displayed significant antimycobacterial activity (IC50 3.7, 6.0, and 7.6 µM, respectively).