OBJECTIVE To investigate the improve-ment functions of flavonoid compounds on temozolomide(TMZ)-,aging-or AD model-induced dysregulation of hip-pocampal NSC lineage progression,retardancy of den-dritic spine maturation in new-born neurons,as well as impairment of hippocampal-related learning and memory.METHODS We applied 30-week-old neural stem cell(NSC)specific promoter Nestin-GFP and NestinCreERT2:Rosa26-LSL-tdTomato transgenic mice and 16-week-old AD model 5XFAD transgenic mice,together with hippo-campal microinjection(ih),endogenous fluorescence trac-ing and immunofluorescent staining.RESULTS Both fla-vonoid compound A and its functional derivative flavo-noid compound B dose-dependently improved TMZ-,aging-or AD-induced defects of hippocampal NSC lin-eage progression and the maturation of dendritic spines of newborn neurons,thereby improving hippocampus related learning and memory.CONCLUSION This paper provides a new idea and treatment strategy for the devel-opment of new flavonoids that can promote neurogene-sis for neurodegenerative diseases and aging.

Objective:To explore the protective effect of Yiqi Fumai Lyophilized Injection (YQFM) on myocardial cell injury induced by doxorubicin and its mechanism.Methods:H9c2 cells were divided into the control group, the doxorubicin group, and the YQFM group. Cells in the control group were given routine incubated. H9c2 cells in the doxorubicin group were given doxorubicin (1 μmol/L) and incubated for 24 h. Cells in the YQFM group were given doxorubicin (1 μmol/L) and YQFM (1.5 mg/L) and incubated for 24 h. The cell viability, cell surface area, atrial natriuretic peptide, and brain natriuretic peptide protein expression levels were detected in each group. The levels of oxidative stress factors, including superoxide dismutase (SOD), malondialdehyde, glutathione peroxidase (GSH-Px) and catalase (CAT) were detected in each group. The apoptosis level, mitochondrial membrane potential, apoptotic associated protein such as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and c-cysteinyl aspartate specific proteinase-3 (c-Caspase-3), p53 and protein expression level of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway were detected in each group.Results:YQFM increased the viability ( P < 0.01), decreased the cell surface area ( P < 0.001), and the levels of atrial natriuretic peptide and brain natriuretic peptide proteins ( P < 0.05) of H9c2 cell in the doxorubicin group. In addition, the SOD, GSH-Px, and CAT levels in the YQFM group were higher than those in the doxorubicin group ( P < 0.05, 0.01), while the malondialdehyde level in the YQFM group was lower than that in the doxorubicin group ( P < 0.05). YQFM also reduced the apoptosis level of H9c2 cell in the doxorubicin group ( P < 0.01), increased the level of mitochondrial membrane potential ( P < 0.01) and the Bcl-2/Bax protein expression level ( P < 0.05), and decreased c-Caspase-3 and p53 protein expression levels ( P < 0.05). It was further found that the p-PI3K and p-Akt protein expression levels in the YQFM group were higher than those in the doxorubicin group ( P < 0.05, 0.01). Conclusions:YQFM can inhibit myocardial cell injury induced by doxorubicin, and its mechanism may be related to the inhibition of oxidative stress and activation of PI3K/Akt pathway.

Background and purpose: Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) plays a cancer-promoting role in many cancers, however its effect on colorectal cancer (CRC) and its regulatory mechanism are not clear. This study aimed to explore the mechanism of lncRNA SNHG5/miR-26a-5p/metadherin (MTDH) signal axis promoting metastasis of CRC. Methods: The data of The Cancer Genome Atlas (TCGA) database was analyzed, the abnormal expression of lncRNA in CRC was explored and analyzed the survival. Samples of CRC, paracancerous tissues and complete clinical data of patients who underwent surgical resection from October 2020 to October 2021 were collected. The expression levels of SNHG5 and miR-26a-5p in lncRNA were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), and the expression level of MTDH was detected by immunohistochemistry. The relationship between the relative expression level of lncRNA SNHG5 in CRC and clinicopathological features and survival time was analyzed. The effects of lncRNA SNHG5 on the proliferation, migration and invasion of CRC cells were detected by cell counting kit-8 (CCK-8), clone formation, scratching assays, transwell test and in vivo xenotransplantation. The relationship between CRC cell metastasis, the expression level of epithelial-mesenchymal transition related molecules and lncRNA SNHG5 expression level by Western blot and immunohistochemical detection were explored. The physical interaction between SNHG5 and miR-26a-5p, MTDH and miR-26a-5p was studied by RNA pull-down test, double luciferase reporter gene detection and RNA co-immunoprecipitation. The functional relationship among the three was verified by CCK-8, EdU and transwell experiments. The effect of SNHG5, miR-26a-5p and MTDH expression on migration and invasion related molecules was analyzed by Western blot. Results: The results of TCGA database analysis showed that lncRNA SNHG5 was significantly upregulated in CRC. The results of RTFQ-PCR and immunohistochemistry showed that the levels of lncRNA SNHG5 and MTDH in CRC tissues were significantly upregulated (P＜0.05), the level of miR-26a-5p was decreased (P＜0.05), and the level of MTDH in samples with high expression of SNHG5 was also increased. The expression of lncRNA SNHG5 in CRC tissues with serosa and extraserosal invasion, distant metastasis, lymph node metastasis and TNM stage Ⅲ was significantly higher compared with subserosal invasion, no distant metastasis and lymph node metastasis and TNM stage Ⅰ-Ⅱ (P＜0.05). The results of survival analysis showed that the high expression of lncRNA SNHG5 was significantly correlated with overall survival rate (P＜0.05). Overexpression of lncRNA SNHG5 could enhance the proliferation, clone formation, migration and invasion of CRC cells, promote the growth and lung metastasis of transplanted tumor, increase the relative expression level of Ki-67 proliferation index and vimentin (P＜0.05), and decrease the relative expression level of E-cadherin (P＜0.05). However, the development of CRC cells was inhibited after inhibition of lncRNA SNHG5 expression. RNA pull-down test, double luciferase reporter gene detection and RNA co-immunoprecipitation confirmed the physical interaction between SNHG5 and miR-26a-5p, MTDH and miR-26a-5p. Upregulation of miR-26a-5p or downregulation of MTDH expression in lncRNA SNHG5 overexpressed cells partially reversed the effects of lncRNA SNHG5 on proliferation, migration, invasion and expression of related molecules in CRC cells. Conclusion: LncRNA SNHG5 is upregulated in CRC tissues and cells, and its high expression is related to tumor progression and poor survival. It can be used as a molecular sponge of miR-26a-5p to regulate the expression of MTDH to promote the proliferation and metastasis of SW620 cells.