Identification of the CCL2 PI3K/Akt axis involved in autophagy and apoptosis after spinal cord injury.

Spinal cord injury (SCI) is a devastating neurological disease with no cure that usually results in irreversible loss of sensory and voluntary motor functions below the injury site. We conducted an in-depth bioinformatics analysis combining the gene expression omnibus spinal cord injury database and the autophagy database and found that the expression of the autophagy gene CCL2 was significantly upregulated and the PI3K/Akt/mTOR signaling pathway was activated after SCI. The results of the bioinformatics analysis were verified by constructing animal and cellular models of SCI. We then used small interfering RNA to inhibit the expression of CCL2 and PI3K to inhibit and activate the PI3K/Akt/mTOR signaling pathway; western blot, immunofluorescence, monodansylcadaverine, and cell flow techniques were used to detect the expression of key proteins involved in downstream autophagy and apoptosis. We found that when PI3K inhibitors were activated, apoptosis decreased, the levels of autophagy-positive proteins LC3-I/LC3-II and Bcl-1 increased, the levels of autophagy-negative protein P62 decreased, the levels of pro-apoptotic proteins Bax and caspase-3 decreased, the levels of the apoptosis-inhibiting protein Bcl-2 increased. In contrast, when a PI3K activator was used, autophagy was inhibited, and apoptosis was increased. This study revealed the effect of CCL2 on autophagy and apoptosis after SCI through the PI3K/Akt/mTOR signaling pathway. By blocking the expression of the autophagy-related gene CCL2, the autophagic protective response can be activated, and apoptosis can be inhibited, which may be a promising strategy for the treatment of SCI.

Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota.

Hyperlipidemia can directly cause metabolic diseases that seriously endanger disorder and metabolism and gut health. Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. This study aimed to investigate the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics. Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. Moreover, EGCG may protect liver function via reducing the glycerophospholipids increased by high-fat diet intervention. TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). The above results provided new insights into the hypolipidemic mechanism of TP and EGCG.

Pyroptosis-related genes play a significant role in the prognosis of gastric cancer.

BACKGROUND: Pyroptosis is an inflammatory form of programmed cell death, which has been shown to be related to the prognosis of many tumors. However, its role in gastric cancer (GC) is not fully understood. AIM: To evaluate the expression of pyroptosis-related genes in GC and its correlation with prognosis. METHODS: We constructed prognostic multigene markers of differentially expressed genes associated with pyroptosis by least absolute contraction and selection operator Cox regression. The risk model was analyzed by Kaplan-Meier curve, two-sided log-rank test and functional enrichment analysis. RESULTS: Sixty-three pyroptosis-related genes were differentially expressed in tumor tissues and adjacent nontumor tissues. Based on these differentially expressed genes, 5 gene signature were constructed and all GC patients were classified into two risk groups. Kaplan-Meier survival curve showed that the overall survival (OS) of patients in the high-risk group was significantly lower than that of the low-risk group. Multivariate Cox regression analyses showed that the risk score was an independent risk factor for OS. Receiver operating characteristic curve analysis confirmed the predictive ability of the model. External validation indicated increased OS in the low-risk group. The immune function and immune cell scores of the high-risk group were generally higher than those of the low-risk group. CONCLUSION: Pyroptosis-related genes play a significant role in tumor immune microenvironment. This novel model, which contains 5 pyroptosis-related genes, is an independent predicting factor for OS in GC patients, and may help to evaluate the prognosis of GC.

[Effectiveness on the education and food safety programs among senior primary students in 2 counties from west China-a cluster randomized trial].

OBJECTIVE: To evaluate the effectiveness of nutrition and food safety educational programs on primary students from grade 4 to 6 in impoverished areas of Western China, under a school-based cluster-randomized trial. METHODS: Twelve primary schools were selected from 2 impoverished counties in West China and assigned to intervention or control groups, randomly, with 6 schools in each group. Self-rating knowledge, attitude and practice questionnaires were used at both baseline and final stages. Textbooks and supportive materials were designed according to the characteristics of baseline data. All students in the intervention group were treated with targeted nutrition and food safety lectures of 0.5 hour per week for 2 semesters. Generalized linear mixed effects model was applied to fit the random effects on individual and clusters as well as to fit the fixed effect of the programs. RESULTS: Three hundred seventy-eight students from grade 4 to 6 were randomly selected at the baseline study and the differences of scores on knowledge, attitude and practice between the 2 groups were statistically insignificant (P > 0.05). No cluster was lost during the trial. In the final investigation, 478 students were randomly selected at the individual level. Scores on knowledge, attitude and practice among students in the intervention group were significantly higher, when comparing to the control group (P < 0.01). At the cluster level, more schools in the intervention group showed significant changes on knowledge and practice, yet the change in attitude was less obvious. Data from the mixed-effects model demonstrated that the program served as an influential factor on scores related to knowledge after the intervention(P = 0.015)but did not affect the scores on related attitude or practice (P > 0.05). CONCLUSION: Lectures seemed to have improved the cognition of nutrition and food safety among primary students from grade 4 to 6. However, long-term observation and larger sample size were needed to evaluate the changes on attitude and practice among the students.

Diarylheptanoids from the Rhizomes of Curcuma kwangsiensis.

Twelve new diarylheptanoids and six known compounds were isolated from rhizomes of Curcuma kwangsiensis. Structures of the new compounds were elucidated by spectroscopic and chemical methods as (3S)- and (3R)-1,7-bis(4-hydroxyphenyl)-(6E)-6-hepten-3-ol (1a and 1b), (3S)- and (3R)-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-(6E)-6-hepten-3-ol (2a and 2b), (3S)- and (3R)-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptan-3-ol (3a and 3b), (3R)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol (4b), (3S)- and (3R)-3-acetoxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-(6E)-6-heptene (5a and 5b), (3S)- and (3R)-3-acetoxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptanes (6a and 6b), and (E)-1,7-bis(4-hydroxyphenyl)-6-hepten-3-one (7). The absolute configurations were determined using the modified Mosher's method. Separation of the enantiomeric mixtures (1a and 1b, 2a and 2b, 3a and 3b, 4a and 4b, 5a and 5b, 6a and 6b) was achieved on a chiral column using acetonitrile-water mixtures as eluents. The S enantiomers exhibited negative specific optical rotations in MeOH, and the R enantiomers were positive. Inhibitory effects of the compounds on nitric oxide production in lipopolysaccaride-activated macrophages were evaluated.