With the aging of the world's population,the incidence of Alzheimer's disease (AD) is continuously increasing.Currently,AD has become one of the most severe challenges faced by modern medicine.Genistein is a flavonoid phytoactive substance,whose structure is similar to that of estrogen,allowing it to mimic the effects of estrogen and possess various biological activities.Due to its multi-pathway targeting and low toxicity characteristics,it is considered to be an effective potential therapeutic source for AD.In this paper,the pharmacokinetics of genistein are introduced,and its neuroprotective effects and mechanisms in AD are reviewed from the aspects of its estrogen-like action,antioxidant,anti-inflammatory,anti-β-amyloid,regulation of cholinergic neurotransmission and inhibition of Tau protein phosphorylation.

Objective:A rare case of δ-globin gene (HBD) mutation in Guangdong Province was analyzed to provide reference for avoiding misdiagnosis of δ-thalassemia in clinic.Methods:The patient was admitted to Guangdong Maternal and Child Health Hospital, and the peripheral blood sample was collected for hematological phenotypes [mean erythrocyte volume (MCV), mean erythrocyte hemoglobin content (MCH), hemoglobin (Hb)] and Hb typing analysis. The routine deletion and mutation of α-thalassemia and β-thalassemia genes were analyzed by PCR-flow fluorescence hybridization. At the same time, DNA sequencing was used to analyze the type of HBD mutation.Results:The results of hematological phenotypes analysis showed that MCV was 87.9 fl, MCH was 29.3 pg, and Hb content was 140 g/L. The results of Hb typing showed that the contents of Hb F, Hb A 2, Hb A 2 variant, and Hb A were 0.4%, 1.3%, 0.6%, and 97.7%, respectively. No abnormality was found in α-thalassemia and β-thalassemia genes by routine deletion and mutation detection. According to DNA sequencing analysis, the patient had HBD: c.349 C>G variant. Conclusion:The low Hb A 2 content (reference value is 2.5% - 3.5%) in this case is due to the mutation of HBD, HBD: c.349 C>G variant is rare in Chinese population.

Objective:To investigate the treatment of an embryo with the partial dissolution of zona pellucida on day 2 and summarize the identification and treatment of embryos without zona pellucida during culture.Methods:A case of one live baby from an embryo with the partial dissolution of zona pellucida transferred on day 2 was retrospectively analyzed.Results:Through reducing the transplant cleaning process, the patient got pregnant and delivered a live girl baby at 39 +3 weeks of gestation. Conclusion:The early dissolution of zona pellucida may affect the compaction process of embryos, but a good outcome can still be obtained by carefully selecting embryos and reducing the washing process of embryo transfer.

Objective:To investigate the treatment of an embryo with the partial dissolution of zona pellucida on day 2 and summarize the identification and treatment of embryos without zona pellucida during culture.Methods:A case of one live baby from an embryo with the partial dissolution of zona pellucida transferred on day 2 was retrospectively analyzed.Results:Through reducing the transplant cleaning process, the patient got pregnant and delivered a live girl baby at 39 +3 weeks of gestation. Conclusion:The early dissolution of zona pellucida may affect the compaction process of embryos, but a good outcome can still be obtained by carefully selecting embryos and reducing the washing process of embryo transfer.

In order to study the signal pathway secreting type Ⅰ interferon in porcine alveolar macrophages (PAMs) infected with porcine circovirus type 2 (PCV2), the protein and the mRNA expression levels of cGAS/STING pathways were analyzed by ELISA, Western blotting and quantitative reverse transcriptase PCR in PAMs infected with PCV2. In addition, the roles of cGAS, STING, TBK1 and NF-κB/P65 in the generation of type I interferon (IFN-I) from PAMs were analyzed by using the cGAS and STING specific siRNA, inhibitors BX795 and BAY 11-7082. The results showed that the expression levels of IFN-I increased significantly at 48 h after infection with PCV2 (P<0.05), the mRNA expression levels of cGAS increased significantly at 48 h and 72 h after infection (P<0.01), the mRNA expression levels of STING increased significantly at 72 h after infection (P<0.01), and the mRNA expression levels of TBK1 and IRF3 increased at 48 h after infection (P<0.01). The protein expression levels of STING, TBK1 and IRF3 in PAMs infected with PCV2 were increased, the content of NF-κB/p65 was decreased, and the nuclear entry of NF-κB/p65 and IRF3 was promoted. After knocking down cGAS or STING expression by siRNA, the expression level of IFN-I was significantly decreased after PCV2 infection for 48 h (P<0.01). BX795 and BAY 11-7082 inhibitors were used to inhibit the expression of IRF3 and NF-κB, the concentration of IFN-I in BX795-treated group was significantly reduced than that of the PCV2 group (P<0.01), while no significant difference was observed between the BAY 11-7028 group and the PCV2 group. The results showed that PAMs infected with PCV2 induced IFN-I secretion through the cGAS/STING/TBK1/IRF3 signaling pathway.
Animals ; Cells, Cultured ; Circovirus ; Interferon Type I/genetics* ; Macrophages, Alveolar/virology* ; Membrane Proteins/metabolism* ; Nucleotidyltransferases/metabolism* ; Signal Transduction ; Swine

Objective:To investigate the regulatory effects and mechanism of mannose-binding lectin(MBL) on autophagy during the differentiation of 3T3-L1 adipocytes, and provide the feasibility for targeting autophagy to prevent obesity and related pathological conditions in natural immunity.Methods:3T3-L1 preadipocytes were cultured in vitro and induced to differentiation. Cell differentiation and lipid accumulation were analyzed by oil red O staining and CCK-8 was used to detect the effect of different concentrations of MBL (0, 1, 5, 10 μg/ml) on cell proliferation ability at different differentiation stages. Western blot was used to analyze the expression of MBL(10 μg/ml) on the key autophagy factors LC3B, Beclin1 and p62 protein at different stages of differentiation, and the changes of lipid droplet accumulation under the intervention of MBL were observed by oil red O staining. The protein and mRNA expression of autophagy key factors under the intervention of different concentrations of MBL were detected by Western blot and qRT-PCR. And autophagy flow analysis based on autophagic degradation was used to further illustrate the autophagic activity. The expression and phosphorylation of adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling molecules were analyzed by Western blot. Results:The results of oil red O staining showed that 3T3-L1 preadipocytes could achieve complete differentiation after 10 days of induction. CCK-8 showed that the concentration of MBL (1-10 μg/ml) in the experimental group had no effect on cell proliferation at different differentiation stages. During the differentiation of 3T3-L1 preadipocytes, Western blot and qRT-PCR showed that the expression of autophagy-related proteins and mRNA levels was enhanced in the MBL treated group, and presented a concentration-dependent relationship. Oil red O staining showed that the lipid droplets in adipocytes at different stages of differentiation are reduced to varying degrees under the intervention of MBL. Fluorescence microscopy results further confirmed that MBL enhanced the autophagy activity of adipocytes by increasing the synthesis of autophagosomes. Moreover, under the intervention of MBL, the phosphorylation level of AMPK was significantly up-regulated, while the phosphorylation level of mTOR was significantly down-regulated, also showing a concentration-dependent relationship.Conclusions:MBL accelerates the autophagy process during the differentiation of 3T3-L1 adipocytes through AMPK/mTOR signaling pathway, reduces lipid accumulation, providing a possible functional pathway for the treatment of obesity and related metabolic diseases.