Correlation between T-Lymphocyte Subsets, Regulatory T Cells, and Hepatic Fibrosis in Patients with Nonalcoholic Fatty Liver.

Objective: The aim of this study is to assess the relationship between T-lymphocyte subsets, regulatory T cells (Treg), and hepatic fibrosis in patients with a nonalcoholic fatty liver disease (NAFLD). Methods: A retrospective analysis was conducted on 64 NAFLD patients (research group) and 73 healthy subjects (control group) in our hospital from January 2020 to December 2021. T-lymphocyte subsets (Th17) and Treg, liver function (alanine aminotransferase (ALT), aspartate aminotransferase (AST)), hepatic fibrosis indexes (type III procollagen (PCIII), type IV collagen (CIV), laminin (LN), hyaluronic acid (HA)), inflammatory factors (high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), interleukin-8 (IL-8)), and oxidative stress (OS) response ((superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA)) were tested. The relationship between Th17/Treg and the abovementioned indexes in NAFLD patients was analyzed. Results: In comparison to the control group, Th17 and Th17/Treg were higher in the research group (P < 0.05). In addition, liver function, liver fibrosis markers, inflammatory factors, and MDA were elevated, while SOD and GSH-PX decreased (P < 0.05). Subsequently, NAFLD patients were divided into groups A (Th17/Treg <1.15, n = 33) and B (Th17/Treg ≥1.15, n = 31) based on their median Th17/Treg levels. It was seen that liver injury, hepatic fibrosis, inflammation, and OS in group A were more severe (P < 0.05). The Pearson correlation coefficient revealed that Th17/Treg was positively correlated with AST, ALT, PCIII, MDA, and inflammatory factors but negatively correlated with SOD and GSH-PX (P < 0.05).

[Preliminary study on cerebrospinal fluid proteomics of Erxian Decoction against neurogenesis impairment in late-onset depression].

This study aims to elucidate the underlying mechanism of Erxian Decoction(EXD) against neurogenesis impairment in late-onset depression(LOD) rats based on cerebrospinal fluid(CSF) proteomics. A total of 66 20-21-month-old male Wistar rats were randomized into naturally aged(AGED) group, LOD group, and EXD group. All rats received chronic unpredictable mild stress(CUMS) for 6 weeks for LOD modeling except for the AGED group. During the modeling, EXD group was given EXD(ig, twice a day at 4 g·kg~(-1)) and other groups received equivalent amount of normal saline(ig). After modeling, a series of behavioral tests, such as sucrose preference test(SPT), open-field test(OFT), forced swimming test(FST), and Morris water maze test(MWMT) were performed. Immunofluorescence method was used to detect the number of Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area of each group. High-concentration corticosterone(CORT) was combined with D-galactose(D-gal) to simulate the changes of LOD-related stress and aging and the proliferation and differentiation of primary neural stem cells of hippocampus in each group were observed. Data independent acquisition(DIA)-mass spectrometry(MS) was used to analyze the differential proteins in CSF among groups and bioinformatics analysis was performed to explore the biological functions of the proteins. Behavioral tests showed that sucrose consumption in SPT, total traveling distance in OFT, and times of crossing the platform in MWMT were all reduced(P<0.01) and the immobility time in FST was prolonged(P<0.01) in the LOD group compared with those in the AGED group, suggesting that LOD rats had developed depression symptoms such as anhedonia, decreased locomotor activity ability, and cognitive dysfunction. Behavioral abnormalities were alleviated(P<0.01, P<0.05) in the EXD group as compared with those in the LOD group. Immunofluorescence results demonstrated that Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area were fewer(P<0.05) in LOD group than in the AGED group, and the positive cells in the EXD group were more(P<0.05) than those in the LOD group. In vitro experiment showed that the proliferation and differentiation of primary hippocampal neural stem cells under the CORT+D-gal treatment were reduced(P<0.01). The proliferation rate of neural stem cells decreased(P<0.05) in CORT+D-gal+LOD-CSF group but increased(P<0.01) in CORT+D-gal+EXD-CSF group compared with that in the CORT+D-gal group. A total of 2 620 proteins were identified from rat CSF, with 135 differential proteins between the LOD group and AGED group and 176 between EXD group and LOD group. GDF11, NrCAM, NTRK2, and GhR were related to neurogenesis and 39 differential proteins were regulated by both LOD and EXD. EXD demonstrated obvious anti-LOD effect, as it improved the locomotor activity ability and cognitive function of LOD rats and protected the proliferation and differentiation of hippocampal neural stem cells. EXD exerts anti-LOD effect by regulating the proteins related to neurogenesis in CSF, such as GDF11, NrCAM, NTRK2, and GhR and maintaining hippocampal neurogenesis.

MYB89 Transcription Factor Represses Seed Oil Accumulation.

In many higher plants, seed oil accumulation is precisely controlled by intricate multilevel regulatory networks, among which transcriptional regulation mainly influences oil biosynthesis. In Arabidopsis (Arabidopsis thaliana), the master positive transcription factors, WRINKLED1 (WRI1) and LEAFY COTYLEDON1-LIKE (L1L), are important for seed oil accumulation. We found that an R2R3-MYB transcription factor, MYB89, was expressed predominantly in developing seeds during maturation. Oil and major fatty acid biosynthesis in seeds was significantly promoted by myb89-1 mutation and MYB89 knockdown; thus, MYB89 was an important repressor during seed oil accumulation. RNA sequencing revealed remarkable up-regulation of numerous genes involved in seed oil accumulation in myb89 seeds at 12 d after pollination. Posttranslational activation of a MYB89-glucocorticoid receptor fusion protein and chromatin immunoprecipitation assays demonstrated that MYB89 inhibited seed oil accumulation by directly repressing WRI1 and five key genes and by indirectly suppressing L1L and 11 key genes involved in oil biosynthesis during seed maturation. These results help us to understand the novel function of MYB89 and provide new insights into the regulatory network of transcriptional factors controlling seed oil accumulation in Arabidopsis.

[Curcumin inhibited hypoxia induced epithelial-mesenchymal transition in hepatic carcinoma cell line HepG2 in vitro].

OBJECTIVE: To explore effects and possible mechanisms of curcumin on hypoxia induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cell line HepG2. METHODS: HepG2 cells were divided to 3 groups, i.e., the normal control group, the CoCl2 group, and the CoCl2 plus 10 micromol/L curcumin group. The proliferation of HepG2 was determined using MTT assay. The migration of HepG2 was detected by wound healing assay.The mRNA expression of hypoxia-inducible factor-1 (HIF-1alpha) was evaluated with real-time RT-PCR. The protein expressions of HIF-1alpha, epithelial-cadherin (E-cadherin), and vimentin were determined using Western blot. RESULTS: Compared with the normal control group, the proliferation and migration of HepG2 cells under CoCl2-induced hypoxia significantly increased, the expression of HIF-1alpha was up-regulated, and the expression of E-cadherin protein was obviously down-regulated, and the expression of vimentin significantly increased (all P < 0.05). Intervention by curcumin significantly inhibited the proliferation and migration of hypoxic HepG2 cells, and expressions of HIF-1alpha and vimentin decreased, and the expression of E-cadherin was up-regulated, showing statistical difference when compared with those of the CoCl2 group (P < 0.05). There was no statistical difference in HIF-1alpha mRNA expression among the 3 groups (P > 0.05). CONCLUSION: Curcumin could reverse the proliferation and migration of HepG2 cells under CoCl2-induced hypoxia condition, which might be associated with inhibiting up-regulated expressions of HIF-1alpha protein and EMT.