AIM:To observe the effects of adipose differentiation-related protein ( adipophilin) on the expres-sion of inflammatory factors in RAW264.7 macrophage and to clarify the related mechanism.METHODS:The cell models with high expression and low expression of adipophilin were constructed by transfecting PA317 packaging cells with stable high or low expression adipophilin retroviral vectors into the RAW264.7 cells.The concentrations of IL-6, MCP-1 and TNF-αin the cell culture medium were detected by ELISA.The protein levels of AP-1, p-AP-1, ERK1/2 and p-ERK1/2 were measured by Western blot.The protein levels of adipophilin, p-ERK1/2 and p-AP-1 and the releases of the inflamma-tory factors in the RAW264.7 cells treated with or without ERK1/2 inhibitor PD98059 or AP-1 inhibitor curcumin were de-termined.RESULTS:The RAW264.7 cells with high expression of adipophilin had higher levels of IL-6, MCP-1 and TNF-α, and higher protein levels of p-AP-1 and p-ERK1/2 than those in the cells with low expression of adipophilin. ERK1/2 inhibitor had no significant effect on the expression of adipophilin, but the protein expression of ERK1/2 and AP-1 was significantly inhibited (P<0.05).The administration of AP-1 inhibitor curcumin had no significant effect on the protein expression of adipophilin and ERK1/2, but the protein expression of AP-1 was significantly inhibited (P<0.05). At the same time, the releases of inflammatory factors IL-6, MCP-1 and TNF-αwere significantly decreased.CONCLU-SION:Adipophilin may regulate the expression of inflammatory factors through ERK1/2-AP-1 pathway in RAW264.7 mac-rophages.

The continuous development of high-throughput and single-cell sequencing technologies and the emergence of spatial transcriptome sequencing have allowed the continuous discovery of temporal and spatial molecular events in the progression of colorectal cancer (CRC) to better understand its mechanism of malignant progression. Genetic variations (mutation of APC and P53, etc.) and mismatch repair of DNA, posttranscriptional regulation, such as epigenetic alteration, and dynamic alteration of complex molecular networks have their own special molecules that play key roles. Drug resistance and metastasis in the late stage of CRC progression are closely related to these key molecular events. This article reviews the research progress and explores key molecular events in the malignant progression of CRC to provide scientific basis and ideas for elucidating the regulatory mechanism of CRC and evaluating its prognosis prediction and treatment.

Objective:To analyze effects of tectorigenin on improving cognitive deficits in rats with vascular dementia(VD)by regulating Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway.Methods:A total of 72 rats were randomly divided into sham operation group,model group,low,medium and high doses[25,50,100 mg/(kg·d)]tectorigenin groups and positive control group[piracetam 324 mg/(kg·d)],with 12 rats in each group.Except for sham operation group,VD models were replicated in other groups.After successful modeling,different doses tectorigenin groups and positive control group were administered intragastrically with different doses of tectorigenin and piracetam,while other groups were administered intragastrically with same volume of normal saline for 28 d.Spatial learning and memory ability were detected by Morris water maze.Neurotransmitter levels in hippocampus interstitial fluid were detected by high performance liquid chromatography-electro-chemical.Brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor b(TrkB)expressions in hippocampus were detected by RT-qPCR and Western blot.TLR4/MyD88/NF-κB pathway-related proteins in hippocampus were detected by Western blot.Results:Compared with sham operation group,escape latency was longer,while stay time in target area and times of crossing platform were lower in model group(P<0.05).Compared with model group,escape latency was shorter,while stay time in target area and times of crossing platform were higher in medium and high doses tectorigenin groups(P<0.05).NE,DA,5-HT and 5-HIAA levels in model group were lower than those in sham operation group(P<0.05),which were higher in medium and high doses tectorigenin groups than model group(P<0.05).Compared with sham operation group,BDNF and TrkB mRNA and proteins levels were lower,while TLR4,MyD88 and p-NF-κB p65/NF-κB p65 proteins levels were higher in model group(P<0.05).Compared with model group,BDNF and TrkB mRNA and proteins levels were higher,while TLR4,MyD88 and p-NF-κB p65/NF-κB p65 proteins levels were lower in medium and high doses tectorigenin groups(P<0.05).Conclusion:Tectorigenin can improve cognitive deficits in VD rats,which may be related to regulating TLR4/MyD88/NF-κB signaling pathway.

OBJECTIVE To study the effects of Dianxianqing granules on the tau protein in P301S mice by regulating mitophagy. METHODS Totally 36 P301S mice were randomly divided into model group， Dianxianqing granule group （12.48 g/kg）， donepezil hydrochloride group （positive control， 1.3 mg/kg）， with 12 mice in each group； another 10 C57BL6 mice were selected as control group. Administration groups were given relevant drug solutions intragastrically， and control group and model group were given constant volume of water intragastrically. The gavage volume was 20 mL/kg， once a day， for consecutive 5 months. During the experiment， the general condition of mice was observed in each group. After the last medication， the learning and memory ability was determined by Y maze test and Morris water maze test； HE staining was used to observe the morphological changes in brain tissue， and Nissl staining was used to observe the structure of neural cells and the number of Nissl bodies in cerebral tissue. Immunohistochemistry was used to detect the expressions of phospho-tau serine 202/threonine 205 （abbreviated as AT8） in brain tissue. Western blot assay was used to determine the expressions of mitophagy-associated proteins [PTEN-induced putative kinase-1 （PINK1）， Parkin， microtubule-associated protein 1 light chain 3B （LC3B）， p62]， synaptic-associated proteins [postsynaptic density protein-95 （PSD-95）， synaptophysin （SYP）， and growth-associated protein-43 （GAP-43）] and the phosphorylation of tau protein [expressed by the phosphorylation levels of serine 199 （Ser199） and Ser202] in brain tissue. RESULTS The mice in E-mail：lnzyxyqy2003@163.com model group showed symptoms such as white hair， decreased body mass， and lower limb paralysis， with incomplete hippocampal structures in their brain tissue， as well as incomplete cell membrane edges and cell structures； the spontaneous alternating response rate， the times of crossing platform， the number of Nissl bodies， the protein expressions of PINK1， Parkin， LC3B， SYP， GAP-43， and PSD-95 were decreased significantly， compared with control group； swimming latency （fourth and fifth day）， the protein expressions of AT8 and p62，the phosphorylation levels of Ser199 and Ser202 were increased or lengthened significantly， compared with control group （P＜0.05 or P＜0.01）. Compared with model group， the above symptoms and indexes of mice were improved significantly in administration groups （P＜0.05 or P＜0.01）. CONCLUSIONS Dianxianqing granules can effectively improve cognitive impairment in P301S mice，the mechanism of which may be associated with inducing mitochondrial autophagy， reducing the hyperphosphorylation of tau protein， up-regulating the expression of synaptic-associated proteins in brain tissue，and repairing damaged neural cells.