BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

OBJECTIVES: To explore the mechanism through which moxibustion promotes endometrial repair in rats with in thin endometrium (TE). METHODS: Female SD rats were randomized into control group, 95% anhydrous ethanol-induced TE model group and moxibustion (at "Guan Yuan") group. High-throughput sequencing was used to identify the target genes of TE, and the targeting relationship between miR-223-3p and NLRP3 was verified using a dual luciferase assay. Histopathological of rat uterus was observed with HE staining, and expressions of miR-223-3p and NLRP3 were detected using RT-qPCR; serum levels of IL-1β and IL-18 of the rats were detected using ELISA, and protein expressions of NLRP3, ASC, caspase-1 and GSDMD in the uterus were detected with Western blotting. The pregnancies of the rats after treatment were counted. RESULTS: Enrichment analysis of the differential genes suggested up-regulated inflammatory response in TE, and dual luciferase assay verified targeted inhibition of NLRP3 expression by miR-223-3p. The rat models of TE had significantly decreased endometrial thickness and reduced endometrial glands and blood vessels with enhanced mRNA expression of NLRP3, increased serum levels of IL-1β and IL-18, up-regulated protein expressions of NLRP3, ASC, caspase-1 and GSDMD, lowered pregnancy rates on both the affected and unaffected sides and the overall number of pregnancies. Treatment of the rat models with mo-xibustion obviously increased the endometrial thickness and the density of glands and blood vessels, up-regulated miR-223-3p expression, lowered serum IL-1β and IL-18 levels and the protein expressions of NLRP3, ASC, caspase-1 and GSDMD, and significantly increased the number of pregnancies. CONCLUSIONS Moxibustion at "Guan Yuan" acupoint up-regulates the expression of miR-223-3p, which results in targeted inhibition of NLRP3 to suppress pyroptosis and promote endometrial repair in rat models of TE.
Animals ; Female ; MicroRNAs/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endometrium/pathology* ; Rats, Sprague-Dawley ; Rats ; Moxibustion ; Pyroptosis ; Up-Regulation ; Interleukin-1beta/metabolism* ; Interleukin-18 ; Caspase 1/metabolism*

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective: To investigate the factors affecting pre-exposure prophylaxis (PrEP) use among men who have sex with men (MSM), so as to provide a basis for improving PrEP uptake among MSM and optimizing HIV prevention and control strategies. Methods: The MSM were recruited at a HIV testing site of the "Danlan Public Welfare" organization in Beijing Municipality using the convenient sampling method from March to May 2024. Sociodemographic information, awareness of basic AIDS knowledge, sexual orientation and behaviors, the use of PrEP and post-exposure prophylaxis (PEP) in the past six months were collected using the questionnaire survey. Multivariable logistic regression model and decision tree model were used to analyze the influencing factors for PrEP use among MSM. Results: A total of 414 participants were surveyed, with a mean age of (33.52±8.50) years. Among them, 345 individuals (83.33%) had a college degree and above. The predominant sexual orientation was homosexual, with 265 individuals, accounting for 64.01%. The majority reported having 1 to 2 same-sex partners in the past six months, with 182 individuals (43.96%). A total of 39 individuals (9.42%) had used PEP in the past six months. A total of 68 individuals (16.43%) had used PrEP during the same period. Multivariable logistic regression analysis revealed that educational attainment (college degree and above, OR=28.200, 95%CI: 3.162-251.519), the number of same-sex partners in the past six months (3-5 partners, OR=3.963, 95%CI: 1.065-14.755; ≥6 partners, OR=7.518, 95%CI: 1.829-30.910), and the use of PEP in the past six months (OR=18.606, 95%CI: 7.587-45.631) were significant factors associated with PrEP use among MSM. The decision tree model identified educational level, sexual orientation, and the number of same-sex partners in the past six months as factors affecting PrEP use among MSM. Among these, the number of same-sex partners in the past six months emerged as the primary influencing factor. The use of PrEP was 38.46% among MSM who had ≥3 same-sex partners in the past six months and identified as homosexual or heterosexual. Conclusion The use of PrEP among MSM is primarily associated with educational level, the number of same-sex partners in the past six months, use of post-exposure prophylaxis (PEP) in the past six months, and sexual orientation.

BACKGROUND:Vascular regeneration,as one of the crucial repair processes after its onset,necessitates visual analysis between the two. OBJECTIVE:To analyze the literature on ischemic stroke and vascular regeneration in the past decade using bibliometrics and sort out the current status,hotspots,and future research trends in this field. METHODS:We used a bibliometric approach to search the Web of Science database for literature on ischemic stroke and vascular regeneration published between January 2011 and May 2023.The obtained data were systematically analyzed using the VOSviewer visualization software to identify the number of articles,countries,keywords,institutions,authors,citations,and trends. RESULTS AND CONCLUSION:We searched and selected 1 484 articles and found that the relationship between ischemic stroke and vascular regeneration has emerged as a research hotspot in the cerebrovascular field,with the number of published articles continuing to rise.Most of these articles were authored by institutions from China and the United States.Shanghai Jiao Tong University was the most cited institution.The most influential author was Hermann DM,whose article had been cited 1 003 times.The current hot research topics in the field include extracellular vesicles,microRNAs and mesenchymal stem cells,which are being studied for their correlations with relevant diseases.To conclude,the bibliometric analysis provides a visual analysis of ischemic stroke and vascular regeneration,which is found to be an emerging focus as well as a valuable reference for future trends and highlights in ischemic stroke and vascular regeneration.

BACKGROUND:Ischemic stroke is a highly prevalent disease associated with apoptosis.Neuronal death occurs after cerebral ischemia,including necrosis and apoptosis.The ischemic core region is dominated by necrosis,while delayed neuronal death in the penumbra is dominated by apoptosis.The penumbra has become a target for the treatment of ischemic stroke.This bibliometric analysis was used to identify the characteristics,hotspots,and frontiers of global scientific output related to apoptosis in ischemic stroke over the past 5 years. OBJECTIVE:To analyze the role of apoptosis and its mechanisms in the pathological process of ischemic stroke through a bibliometric approach. METHODS:A total of 927 relevant literature records from 2018 to 2022 were retrieved from Science Citation Index Expanded(SCI-Expanded)and Social Science Citation Index Expanded(SSCI-Expanded)of the Web of Science Core Collection.Research trends and hotspots of apoptosis in ischemic stroke were visualized using Citespace,VOSviewer and Bibliometrix. RESULTS AND CONCLUSION:From 2018 to 2020,the number of papers on the role of apoptosis in ischemic stroke showed an upward trend,but in 2020,the number of papers began to reduce.China had the largest number of publications,and the United States ranked the second.Capital Medical University and BRAIN RESEARCH BULLETIN were the institutions and journals with the most articles,respectively.In recent years,the two keywords"expression"and"oxidative stress"have appeared more frequently.The bibliometric study showed that in the past 5 years,most of the studies focused on basic research,in which research on the role of apoptosis in ischemic stroke has gradually decreased in the last 3 years,showing a downward trend.On the contrary,nerve regeneration has gradually become a research hotspot,especially the regulation of neurotrophic factors under the influence of different mechanisms,and the research on angiogenesis and glial cell repair is on the rise.At the same time,apoptosis in nerve regeneration is a potential point of discovery.

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.

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.

Objective:To explore the inhaled allergen sensitization status of children with allergic rhinitis in Beijing City, and to provide evidence for diagnosis and treatment, allergen avoidance and disease management.Methods:In this cross-sectional study, data from 8 741 children with allergic rhinitis treated in Children′s Hospital affiliated to Capital Institute of Pediatrics from January 2020 to December 2021 were retrospectively analyzed. The subjects were divided into toddlers (1 y-≤3 y), preschool children (3 y-≤6 y), school aged children (6 y-≤12 y) and adolescents (12 y-≤18 y) and according to season the subjects were divided 4 groups: spring, summer, autumn, winter. The ImmunoCAP system was used to detect serum allergens sIgE.Results:The positive rates of inhaled allergens among subjects in sequence from high to low were: mx2 [molds (penicillium speciosum/mycosporum multiflorum/aspergillus fumigatus/alternatia/demodex longum)], w6 (artemisiaargyi), wx5[weeds pollen combination (ragweed/artemisia argyi/marguerite/dandelion/goldenrod)], w1(ragweed), tx5[trees pollen combination (populus tomentosa/hazel/elm/willow)], d2(dermatophagoides farina), d1(dermatophagoides pteronyssinus), ex1[animal dander combination (catdander/dogdander/horsedander/cowdander)], i6(blattella germanica). Boys have higher positive rates of sIgE responses than girls (54.20% vs. 47.96%, χ 2= 8 923.000, P<0. 001). The primacy inhaled allergen in toddlers, preschool children and school aged children was mx2 (37.75%, 39.99% and 42.46%), and in adolescents w6 (45.45%), d2 (41.51%) and d1 (37.74%) were the largest categories. Except for mold, the positive detection rate of inhaled allergens increased gradually with age. In different seasons, the positive rates of ex1 (24.77% vs. 18.26% vs. 17.10% vs. 12.39%, χ 2= 31.469, P<0.001), wx5 (20.18% vs. 28.62% vs. 39.96% vs. 12.53%, χ 2= 155.788, P<0.001), mx2 (31.79% vs. 50.96% vs. 36.99 vs. 28.81, χ 2= 208.444, P<0.001), tx5 (28.14% vs. 27.01% vs. 26.77% vs. 9.64%, χ 2= 60.613, P<0.001) and w6 (26.57% vs. 34.39% vs. 52.11% vs. 25.35%, χ 2= 17.710, P<0.001) were statistically different among groups. Mx2 in spring and summer was the highest categories (31.79%, 50.96%), and w6 in autumn was the highest (52.11%). Conclusions:In this study, mx2 was the most important allergen in children (≤12 y) and w6 was the highest in adolescents treated in Children′s Hospital affiliated to Capital Institute of Pediatrics from January 2020 to December 2021 in Beijing City. The types of allergens and positivity rates were different for different sexes, ages and seasons.