Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis: A Systematic Review.

Objective: This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD. Methods: We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression ( n = 113,154) and MDD ( n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation. Results: The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression. Conclusion: This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.

Cinnamaldehyde promotes root branching by regulating endogenous hydrogen sulfide.

BACKGROUND: Cinnamaldehyde (CA) has been widely applied in medicine and food preservation. However, whether and how CA regulates plant physiology is largely unknown. To address these gaps, the present study investigated the beneficial effect of CA on root branching and its possible biochemical mechanism. RESULTS: The lateral root (LR) formation of pepper seedlings could be markedly induced by CA at specific concentrations without any inhibitory effect on primary root (PR) growth. CA could induce the generation of endogenous hydrogen sulfide (H2S) by increasing the activity of L-cysteine desulfhydrase in roots. By fluorescently tracking endogenous H2S in situ, it could be clearly observed that H2S accumulated in the outer layer cells of the PR where LRs emerge. Sodium hydrosulfide (H2S donor) treatment induced LR formation, while hypotaurine (H2S scavenger) showed an adverse effect. The addition of hypotaurine mitigated the CA-induced increase in endogenous H2S level, which in turn counteracted the inducible effect of CA on LR formation. CONCLUSION: CA showed great potential in promoting LR formation, which was mediated by endogenous H2S. These results not only shed new light on the application of CA in agriculture but also extend the knowledge of H2S signaling in the regulation of root branching.

[Effect of Schistosoma japonicum infection on serum lipid status in mice].

OBJECTIVE: To investigate the effect of Schistosoma japonicum infection on lipid status in mouse serum. METHODS: Twenty-four ICR mice were randomly divided into two groups, fed a high fat diet (HFD) or a normal diet (ND). On the 28th day, 6 mice from each group were infected with double sex cercariae of S. japonicum via abdominal skin (150 cercariae/mouse). At 42 days post-infection, the mice were sacrificed and the sera were collected. Other 36 ICR mice were randomly divided into three groups fed on normal diet. Mice in the first group were infected with S. japonicum single-sex cercariae via abdominal skin (150 cercariae/mouse) and sacrificed on Day 42. Mice in the second group were intraperitoneally injected with 10,000 S. japonicum eggs and serum samples were collected at Day 4 and Day 7. Mice in the third group were intraperitoneally injected with soluble egg antigen (SEA) every day for 6 days [1 mg/(mice x d)] and serum was collected at Day 7. Mice from control group were fed a high fat diet or a normal diet without infection. Serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low density lipoprotein (LDL) were measured. RESULTS: Compared with the uninfected controls, the serum levels of TC, TG, HDL, and LDL decreased significantly in double-sex cercariae infected-mice fed on a high fat diet or a normal diet (P < 0.05). In HFD group, serum TC[(1.45 +/- 0.31) mmol/L], TG [(0.17 +/- 0.06)mmol/L], HDL [(1.11 +/- 0.26) mmol/L] and LDL [(0.44 +/- 0.15)mmol/L] levels in mice infected with double-sex cercariae were lower than that of uninfected mice [(7.86 +/- 0.07)mmol/L, (0.23 +/- 0.07) mmol/L, (4.96 +/- 0.81) mmol/L, (3.93 +/- 0.29) mmol/L] (P < 0.05) . In ND group, serum TC [(1.03 +/- 0.08) mmol/L] , TG [(0.17 +/- 0.03) mmol/L], HDL [(0.84 +/- 0.02) mmol/L], and LDL [(0.09 +/- 0.02) mmol/L] levels in mice infected with double-sex cercariae were lower than that of uninfected mice [(1.85 +/- 0.05) mmol/L, (0.90 +/- 0.14) mmol/L (1.38 +/- 0.18) mmol/L, (0.15 +/- 0.01) mmol/L, respectively] (P < 0.05) . The mice serum lipid indices had no obvious change after single-sex cercariae or egg injection (P > 0.05). Serum TC [(1.07 +/- 0.15) mmol/L], TG [(1.06 +/- 0.15) mmol/L], HDL [(0.71 +/- 0.14) mmol/L], and LDL [(0.05 +/- 0.04) mmol/L] levels in SEA injected mice were lower than that of the control group [(1.81 +/- 0.06) mmol/L, (2.15 +/- 0.13) mmol/L, (1.160.15) mmol/L, (0.16 +/- 0.03) mmol/L] (P < 0.05). CONCLUSION: Schistosoma japonicum infection can decrease serum lipid concentrations in the mouse host.

[Identification of glycosylphosphatidylinositol-anchored protein from Schistosoma japonicum].

OBJECTIVE: To identify glycosylphosphatidylinositol (GPI) anchored protein of Schistosoma japonicum. METHODS: Based on the gene sequence of Schistosoma mansoni GPI anchored protein Sm200 (GenBank Assess No: XM_002569560.1), bioinformatics analysis was performed to find out its homologous gene sequence in S. japonicum, then a selected partial coding sequence (SjGPIs, about 933 bp) from the homologous gene sequence were amplified, and cloned into PET-28a(+) vector. The recombinant plasmid pET-28a(+)SjGPIs were transformed into E. coli Top10 cells and induced with IPTG for protein expression. The recombinant protein SjGPIs was purified with Ni-NTA resin, and the purified recombinant SjGPIs protein was used as antigen to prepare antiserum in New Zealand rabbit. The antiserum was used to detect S. japonicum GPI-anchored protein. To identify a GPI-anchored protein, the detected protein were identified by phosphatidylinositol-specific phospholipase C (PI-PLC) digestion. White blood cells from S. japonicum-infected mice was examined whether they endocytosed GPI-anchored proteins by Western blotting. RESULTS: The homologous gene sequence of S. mansoni GPI Sm200 gene was found in S. japonicum genome. A 3 495 bp coding sequence was obtained, containing the complete C-terminal sequence. The selected gene sequence (SjGPIs) were amplified and the recombinant plasmid pET-28a(+)-SjGPIs was established. According to the analysis of C-terminal sequence, Western blotting and enzyme digestion of PI-PLC, a GPI-anchored protein was present in S. japonicum tegument (about 1M(r)200000), named SjGPI200. The protein was detected in white blood cells of infected mice. CONCLUSION: SjGPI200 protein exists in S. japonicum, and anchored to parasite tegument via GPI.

Degradation of microcystin-LR and RR by a Stenotrophomonas sp. strain EMS isolated from Lake Taihu, China.

A bacterial strain EMS with the capability of degrading microcystins (MCs) was isolated from Lake Taihu, China. The bacterium was tentatively identified as a Stenotrophomonas sp. The bacterium could completely consume MC-LR and MC-RR within 24 hours at a concentration of 0.7 microg/mL and 1.7 microg/mL, respectively. The degradation of MC-LR and MC-RR by EMS occurred preferentially in an alkaline environment. In addition, mlrA gene involved in the degradation of MC-LR and MC-RR was detected in EMS. Due to the limited literature this gene has rare homologues. Sequencing analysis of the translated protein from mlrA suggested that MlrA might be a transmembrane protein, which suggests a possible new protease family having unique function.