The role and mechanism of TLRs/MyD88/NF-κB signaling pathway in multiple sclerosis / 中国组织工程研究

BACKGROUND:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells.The Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway plays an important role in the development of the disease.Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE:To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models,which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS:The literature related to the topic from January 2002 to December 2022 was searched in CNKI,WanFang and PubMed databases.A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION:The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response.The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells,destroying the integrity of the blood-brain barrier,and promoting the activation of T cells,B cells and microglia.By targeting TLRs,MyD88 and NF-κB molecules,inhibiting the activation or signal transduction of TLRs,MyD88 and NF-κB,and reducing the secretion of pro-inflammatory factors,multiple sclerosis can be treated.Animal studies have shown that active ingredients of traditional Chinese medicines,such as flavonoids and glycosides,and traditional Chinese medicine compound formulas,such as Buyang Huanwu Tang,can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway,which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis.

Astragaloside inhibits astrocyte activation and inflammatory response induced by inflammation / 中国组织工程研究

BACKGROUND:Astrocytes play an important role in the pathology of central nervous system diseases.The phenotypic and functional changes in astrocytes suggest that it may be an effective therapeutic target for central nervous system diseases.Our previous studies have confirmed that astragaloside can inhibit the lipopolysaccharide-induced astrocyte inflammatory response.Whether astragaloside can regulate the phenotype and function of astrocytes through Notch-1 and its downstream signaling pathway remains unclear. OBJECTIVE:To explore the effect of astragaloside on astrocyte activation and inflammatory response induced by inflammation and its possible mechanism. METHODS:Cerebral cortex astrocytes derived from neonatal C57BL/6 mouse were cultured in vitro.CCK-8 assay was used to determine the optimum concentration of astragaloside and Notch active inhibitor DAPT.The astrocytes were divided into five groups:PBS group,lipopolysaccharide group,lipopolysaccharide + astragaloside group,lipopolysaccharide + DAPT group and lipopolysaccharide + DAPT + astragaloside group.The secretion level of inflammatory factors was detected by ELISA,and the level of nitric oxide was detected by Griess method.The astrocytes and splenic mononuclear cells were co-cultured in Transwell chamber to observe the migration of CD4T cells.The expression of astrocyte activation marker GFAP,A1 marker C3 and A2 marker S100A10 as well as Notch 1 and Jag-1 was detected by immunofluorescence staining.The expressions of CFB,C3,S100A10,PTX3,Notch-1,Jag-1,and Hes were detected by western blot assay. RESULTS AND CONCLUSION:(1)According to the results of CCK8 assay,the final concentration of astragaloside was selected as 25 μmol/L and the final concentration of DAPT was 50 μmol/L for follow-up experiments.(2)Compared with PBS group,interleukin-6,interleukin-12 and nitric oxide secretion levels in the lipopolysaccharide group were significantly increased(P<0.05,P<0.05,P<0.01).Compared with the lipopolysaccharide group,interleukin-6(all P<0.05),interleukin-12(P>0.05,P<0.05,P<0.05)and nitric oxide(P<0.05,P<0.01,P<0.01)secretion significantly reduced in the lipopolysaccharide + astragaloside group,lipopolysaccharide +DAPT group,lipopolysaccharide + DAPT + astragaloside group.(3)Compared with the PBS group,the expression of GFAP that is the marker of activated astrocytes and the migration of CD4 T cells were significantly increased in the lipopolysaccharide group(P<0.01).Compared with the lipopolysaccharide group,astrocyte activation was significantly inhibited and CD4 T cell migration was significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group(P<0.05,P<0.05,P<0.01).(4)Compared with the PBS group,the expressions of A1 markers C3 and CFB in the lipopolysaccharide group were increased(P<0.01,P<0.05),and the expressions of A2 markers S100A10 and PTX3 were decreased(P<0.01,P<0.05).Compared with the lipopolysaccharide group,C3(all P<0.01)and CFB(both P<0.05)were significantly reduced and S100A10(all P<0.01)and PTX3(P<0.05,P<0.05 and P>0.05)were increased in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(5)Compared with the PBS group,the expressions of Jag-1,Notch-1 and Hes in the lipopolysaccharide group were significantly increased(all P<0.01).Compared with the lipopolysaccharide group,the expressions of Jag-1(all P<0.01),Notch-1(all P<0.01)and Hes(P<0.05,P<0.01 and P<0.01)were significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(6)The results indicate that astragaloside can promote the transformation of astrocytes from A1 to A2 by regulating Notch-1 signaling pathway,reduce the secretion of inflammatory factors and the migration of CD4 T cells,and thus inhibit astrocyte activation and inflammatory response.

Microanatomy relation of carotid artery bifurcation with lateral branch of the superior laryngeal nerve / 中华神经医学杂志

Objective To discuss the microsurgical anatomy of carotid bifurcation and external branch of the superior laryngeal nerve (EBSLN),and to explore the operative techniques in carotid endarterectomy.Methods The carotid bifurcation (20 sides) of 10 cadaveric heads was studied by using microanatomy from January 2017 to January 2018.The distance between bifurcation of carotid artery to peripheral bone structure,and the distances between point of EBSLN to medial margin of the carotid artery to mandibular angle,most prominent point of the larynx,apex of the mastoid,and bifurcation of carotid artery were measured.Results (1) The vertical distance from carotid bifurcation to larynx point and mandibular angle was 24.32 (18.8-35.78) mm and 13.55 (9.26-19.60) mm.The straight distance from carotid bifurcation to mastoid tip was 68.59 (49.48-76.94) ram.According to the vertical distance of larynx point to carotid bifurcation,the height of bifurcation of the carotid artery was consistent with the results of wain measurement (K=0.90),and the difference was statistically significant (P＜0.05).(2) The distances between the point of EBSLN to medial margin of the carotid artery to carotid artery bifurcation,upper thyroid artery bifurcation,mandibular angle and mastoid process were 17.81 (15.24-25.58) mm,19.42 (17.08-29.12) mm,20.51 (17.98-22.20) mm,71.00 (69.00-74.50) mm in normal bifurcations.Those in the high bifurcation specimens were 6.40 (2.44-9.20) mm,8.84(4.74-10.88) mm,12.15(10.64-13.54),60.90 (59.80-66.50) mm,respectively.Conclusions The position of the laryngeal prominence is fixed,which can be used as a marker for surgical incision.When the vertical distance from the larynx point to the bifurcation of the carotid artery is greater than or equal to 2.5 cm,it is highly bifurcated;the bifurcation is normal when less than 2.5 cm.In patients with normal carotid bifurcation,1.5 cm of the carotid artery bifurcation can be used as a safety mark limit during the operation.For patients with high carotid artery,the EBSLN is almost parallel to or down the superior thyroid artery,and it should be closely attached to the bifurcation of the carotid artery and the outer membrane of the superior thyroid artery,and there is no safety margin.

Aluminum and benzo[a]pyrene co-operate to induce neuronal apoptosis in vitro.

Toxic and harmful factors co-exist in the environment; these factors often interact to induce combined toxicity, which is the main focus of toxicological research. Furthermore, a large number of studies have shown that aluminum (Al) and benzo[a]pyrene (BaP) are neurotoxic and target the central nervous system to cause neuronal apoptosis. Because we are exposed to both Al and BaP in the air, water, food, and even medicine, the combined effects of these agents in humans must be examined. The present study examines the ability of Al and BaP co-exposure to intensify neuronal apoptosis. The primary neurons of newborn rats were cultured for 5 days, and cells from the same batch that were growing well were selected and assigned to the blank control group, the solvent control group (DMSO+S9+maltol), BaP groups (10, 40 µmol/L), Al (mal)3 groups (50, 100, 400 µmol/L) and co-exposure groups with different combinations of BaP and Al (mal)3. The cell viabilities indicated that 10 µM BaP or 50 µM Al (mal)3 was mildly toxic, and we selected 10 µM BaP+50 µM Al (mal)3 for subsequent co-exposure experiments. The morphological characteristics of cell apoptosis were much more obvious in the co-exposure group than in the Al-exposed cells or the BaP-exposed cells, as observed with a transmission electron microscope and a fluorescence inverted microscope. The apoptotic rates and caspase-3 activity quantitatively significantly differed between the co-exposure and Al-exposure groups, while the BaP-exposure group did not significantly differ from the control group. These results indicate that Al and BaP co-exposure exert synergistic effects on neuronal cell apoptosis.

PCD-hIL-2 and Chinese medicine accelerate the immunofunction reconstitution in bone marrow transplantation mice / 北京大学学报(医学版)

Objective: In order to study how to accelerate the reconstitution immunofunction in BMT mice, first of all, we established a immunodeficiency model of BMT in BALB/C mice. Then BMT mice were injected with PCD-hIL-2 directly into skeletal muscle, and treated with traditional Chinese medicine. Methods: The experiment groups are designed as（A）Chinese medicine + PCD-hIL-2;（B）PCD-hIL-2;（C）Chinese medicine +hIL-2;（D）Chinese medicine;（E）hIL-2;（F）BMT;（G）normal control;（H）radiation control. Results: We compared groups A B C D to E or F groups, found（1）The splenocytes/thymocytes count increase obviously.（2）Killing activity of NK cell rises obviously in vivo.（3）The response of splenocytes、thymocytes、BM cells to mitogen goes up.（4）The reactivity of splenocytes to foreign IL-2 goes up. （5）CFU-GM count is increased. Conclusion: The expression of hIL-2 is very low by nude DNA injection ,but it is enough to have biological function and therapeutic effect .If only Chinese medicine was applied, the immunological condition was obviously recovered.

Apoptosis of Keratinocytes and Psoriasis / 中华皮肤科杂志

In order to study the status of cell apoptosis in psoriatic epidermis, we have investigated the changes of the lesions in various stages in patients with psoriasis vulgaris by using terminal deoxynueleotidyl transferase-mediation dUTP-biotin nick end labelling (TUNEL). The results showed that the highest frequency of apoptotic keratinocytes was observed in the early scaling papular lesions, and the frequency was reduced in the progressive maculo-papular lesions and the coalescent plaques successively. The frequency of hyperproliferation of epidermis was in the reverse order in comparison with the above results. These results suggest that increased apoptosis of keratinocytes is the initial change of psoriatic epidermis, then hyperproliferation of keratinoeytes follows.