Elimination diet in food allergy: friend or foe?

Abstract Objectives To review and discuss the role of an elimination diet in food-allergic children, emphasizing nutritional aspects for a better practical approach. Sources Non-systematic review of the literature. Findings Under an elimination diet, food-allergic patients may suffer from growth impairment or obesity and compromised quality of life. Disease phenotype, age, type, number of foods excluded, comorbidities, eating difficulties, economic status, and food availability must be considered for an appropriate diet prescription. Diet quality encompasses diversity and degree of food processing, which may alter immune regulation. Conclusions A friendly food elimination diet prescription depends on a multidisciplinary approach beyond macro and micronutrients.

Evaluation value of serum AGEs level combined with LIS score on prognosis of elderly patients with sepsis-related ALI/ARDS / 国际检验医学杂志

Objective To study the evaluation value of lung injury score(LIS)and advanced glycation end products(AGEs)expression levels on the prognosis of elderly patients with sepsis-related acute lung injury/acute respiratory distress syndrome(ALI/ARDS).Methods A total of 98 elderly patients with sepsis-related ALI/ARDS admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University from March 2019 to April 2021 were selected as the research group,and the patients were divided into two sub-groups according to their survival within 30 d after admission:the survival group(55 cases)and the death group(43 cases).Another 51 elderly patients with non-ALI/ARDS sepsis admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University in the same period were selected as the control group.After admission,the clinical data of patients were recorded,and the levels of serum creatinine,troponin I,B-type brain natriuretic peptide(BNP),serum C-reactive protein(CRP)and procalcitonin(PCT)were de-tected.Enzyme-linked immunosorbent assay was used to determine the levels of AGEs in patients'serum.The LIS score was evaluated by LIS scale.With clinical factors as independent variables and prognosis as dependent variables,Logistic regression curve was used to analyze the death factors of elderly sepsis-related ALI/ARDS patients.Results AGEs levels,LIS scores,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores decreased sequentially in the death group,survival group,and control group(all P<0.05).The levels of lactic acid,blood glucose,troponin I,PCT,BNP and CRP in arterial blood of patients in the death group were significantly higher than those in the survival group and the control group(P<0.05).The results showed that arterial lactate,blood glucose,troponin I,PCT,BNP,CRP,AGEs,APACHE Ⅱ score,and LIS score were all independent risk factors for mortality in elderly sepsis-related ALI/ARDS patients(P<0.05).The area under the curve(AUC)of LIS score predicting prognosis in elderly sepsis-related ALI/ARDS pa-tients was 0.857(95%CI:0.821-0.911),and AUC of serum AGEs was 0.861(95%CI:0.809-0.908).LIS score and AGEs level had certain predictive value for the prognosis of elderly sepsis-related ALI/ARDS pa-tients.Conclusion The LIS score and AGEs level of the elderly patients with sepsis-related ALI/ARDS are independent risk factors of death,which have important predictive value for prognosis.

Expression and prognostic value of serum RAGE and CXCL16 in patients with sepsis complicated with acute respiratory distress syndrome / 国际检验医学杂志

Objective To investigate the expression and prognostic value of serum receptor for advanced glycation end products(RAGE)and CXC-chemokine ligand 16(CXCL16)in patients with sepsis complicated with acute respiratory distress syndrome(ARDS).Methods A total of 234 patients with sepsis diagnosed and treated in a hospital from January 2019 to January 2022 were selected as the study subjects,and were divided into 82 patients with sepsis complicated with ARDS(ARDS group)and 152 patients with sepsis without ARDS(non-ARDS group)according to whether the subjects were complicated with ARDS.ARDS group was divided into survival group(n=50)and death group(n=32)according to the survival status within 28 days of admission.Another 60 healthy subjects who underwent physical examination in the same period were se-lected as the control group.Serum RAGE and CXCL16 levels were detected by enzyme-linked immunosorbent assay.Pearson correlation analysis of serum RAGE and CXCL16 levels with sequential organ failure assess-ment(SOFA)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score and oxygenation index in patients with sepsis and ARDS.Multivariate Logistic regression analysis of prognostic factors of sep-sis complicated with ARDS.The predictive value of serum RAGE and CXCL16 on the prognosis of sepsis complicated with ARDS patients was analyzed by receiver operating characteristic curve.Results The serum RAGE and CXCL16 levels in ARDS group were higher than those in non-ARDS group and control group,and the serum RAGE and CXCL16 levels in non-ARDS group were higher than those in control group,the differ-ence was statistically significant(P＜0.05).Compared with the survival group,the mechanical ventilation time,intensive care unit stay time,procalcitonin,SOFA score,APACHE Ⅱ score,serum RAGE,CXCL16 lev-els were higher in the death group,and the oxygenation index was lower,with statistical significance(all P＜0.05).The serum RAGE level in patients with sepsis complicated with ARDS was positively correlated with SOFA score and APACHE Ⅱ score(r=0.603,0.671,P＜0.05).Serum CXCL16 levels were positively corre-lated with SOFA score and APACHE Ⅱ score(r=0.655,0.707,P＜0.05).Serum RAGE and CXCL16 were negatively correlated with oxygenation index(r=-0.712,-0.683,P＜0.05).Multi-factor Logistics regres-sion analysis showed that serum RAGE and CXCL16 were independent risk factors for death within 28 days of admission in patients with sepsis complicated with ARDS.The area under the curve(AUC)of combined de-tection of serum RAGE and CXCL16 for predicting death within 28 days of admission in patients with sepsis complicated with ARDS was 0.882,which was higher than that of single index detection of serum RAGE and CXCL16,and the difference was statistically significant(Z=4.450,4.906,P＜0.05).Conclusion The com-bined detection of serum RAGE and CXCL16 is helpful to evaluate the clinical prognosis of sepsis complicated with ARDS patients.

Correlation of serum RAGE and HMGB1 expression with the occurrence of acute respiratory distress syndrome and IFN-γ/IL-4 ratio in patients with severe pneumonia / 实用医学杂志

Objective To explore the correlation between the expression level of serum Receptor for Advanced Glycation End-Product(RAGE)and High-Mobility Group Protein B1(HMGB1)expression with the occurrence of acute respiratory distress syndrome(ARDS)and interferon-γ/interleukin-4(IFN-γ/IL-4)ratio in patients with severe pneumonia(SP).Methods A prospective investigation was carried out on one hundred children with SP admitted to our hospital from March 2020 to February 2022,and the participants were classified into ARDS group(n = 56)and control group(n = 44)based on the occurrence of secondary ARDS.General informations werec-ollected.The expression of RAGE,HMGB1,IFN-γ and IL-4 in peripheral blood was measured using Enzyme-Linked Immunosorbent Assay(ELISA).Then multivariate Logistic regression analysis was conducted to screen the influencing factors of secondary ARDS in SP children,and the correlation with IFN-γ/IL-4 ratio was verified by pearson correla-tion analysis,moreover,receiver operating characteristic(ROC)curve was plotted to evaluate the value of RAGE and HMGB1 expression in predicting the occurrence of ARDS in SP children.Results There were no statistical difference in gender,age,body temperature and onset season between the two SP groups.The ARDS group had more types of pathogenic bacteria,larger ratio of the partial pressure of oxygen in arterial blood to the inspired oxygen fraction(PaO2/FiO2),higher Acute Physiological Score(APS),and up-regulated expression of RAGE,HMGB1,IFN-γ and IL-4,as well as larger IFN-γ/IL-4 ratio than those of control group,with statistical difference(all P<0.05).Multivariate Logistic regression analysis revealed that pathogen type,PaO2/FiO2 ratio,RAGE,HMGB1,IFN-γ,IL-4 and IFN-γ/IL-4 were the influencing factors for the occurrence of ARDS in children with SP.Pearson correlation test denoted that the serum RAGE and HMGB1 expression levels of SP children were positively correlated with IFN-γ,IL-4 and IFN-γ/IL-4 ratio(P<0.05).ROC curve found that the AUC of serum RAGE and HMGB1 in predicting the occurrence of ARDS in SP children was 0.707 and 0.750,with a sensitivity of 73.2%and 64.3%,and a specificity of 68.2%and 77.3%.The combined test of RAGE and HMGB1 in predicting the occurrence of ARDS in SP children reached an AUC of 0.848,providing a sensitivity and specificity of 80.4%and 81.8%respectively.Conclusions Serum RAGE and HMGB1 expression levels are elevated in SP children with ARDS,and the two are positively correlated with IFN-γ/IL-4 ratio.Therefore,monitoring serum RAGE and HMGB1 expression in children with ARDS secondary to SP has predictive value for the risk of ARDS in SP children.

Liuwei Dihuang Pills-elicited inhibition of MMP-2/MMP-9 via RAGE on tight junction protein of Aβ1-40-injured bEnd.3 cells / 中成药

AIM To investigate the protective effects and the mechanism of the Liuwei Dihuang Pills on mouse brain microvascular endothelial(bEnd.3)cells damaged by β-Amyloid protein1-40(Aβ1-40).METHODS CCK8 method was used to detect the effects of Aβ1-40 and medicated serum of Liuwei Dihuang Pills(MSLDP)on cell activity,and to screen the appropriate concentration.bEnd.3 cells of the control group,the Aβ1-40 group,the MSLDP+Aβ1-40 group and the MSLDP group had their low density lipoprotein-associated protein 1(LRP1),receptor for advanced glycation end products(RAGE),matrix metalloproteinase-2(MMP-2),MMP-9,scaffold protein zonule protein-1(ZO-1)detected by Western blot.bEnd.3 cells assigned into the control group,the Aβ1-40 group,the FPS-ZM1(RAGE inhibitor)+Aβ1-40 group and the FPS-ZM1+Aβ1-40+MSLDP group had their expressions of RAGE,MMP-9,MMP-2 and ZO-1 detected by Western blot as well.RESULTS The cell activity of bEnd.3,was dose-dependently decreased by Aβ1-40(P<0.01),but was protected by MSLDP(P<0.05,P<0.01).And 10 μmol/L Aβ1-40 and 10%MSLDP were selected for subsequent experiments.Compared with the control group,the Aβ1-40 group displayed increased protein expressions of RAGE,MMP-2 and MMP-9(P<0.01),decreased protein expressions of LRP1,ZO-1 and BDNF(P<0.05,P<0.01),and decreased fluorescence intensities of LRP1 and ZO-1(P<0.01).Compared with the Aβ1-40 group,the MSLDP group shared decreased expressions of RAGE,MMP-2,MMP-9 proteins and RAGE fluorescence intensity(P<0.05,P<0.01),and increased expressions of LRP1,ZO-1 and BDNF proteins,and the fluorescence intensity of LRP1 and ZO-1(P<0.05,P<0.01);the Aβ1-40+FPS-ZM1 group displayed decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.05,P<0.01),and increased ZO-1 protein expression(P<0.05);and the Aβ1-40+FPS-ZM1+ MSLDP group displayed an even more decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.01),increased ZO-1 protein expression(P<0.01)due to the the combination use of FPS-ZM1 and MSLDP.CONCLUSION Liuwei Dihuang Pills can protect the tight junction of bEnd.3 injured by Aβ1-40 and neurovascular units from Alzheimer's disease by alleviating the dysfunction of the blood-brain barrier via RAGE-mediated MMP-2/MMP-9 pathway inhibition.

Mechanism of Yitangkang Granule in Promoting Podocyte Autophagy Through Regulation of PI3K/Akt/FoxO1 Signaling Pathway Mediated by SIRT1 via AGE-RAGE Axis / 中国实验方剂学杂志

ObjectiveTo explore the underlying mechanism by which the Chinese medicine compound Yitangkang granule（YTK） treats diabetic kidney disease （DKD） by observing its effects on podocyte autophagy through the regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead transcription factor O1 （FoxO1） signaling pathway mediated by silent information regulator 1 （SIRT1） via advanced glycation end products （AGE）/receptor for AGE （RAGE） axis. MethodNinety-six 8-week-old healthy male SPF-grade Wistar rats were selected and randomly divided into blank control group （B）， model control group， high-dose YTK （40 g·kg-1）， medium-dose YTK （20 g·kg-1）， low-dose YTK （10 g·kg-1）， and Western medicine control （20 mg·kg-1 losartan） groups. The DKD rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats in each group received the corresponding treatments for eight weeks. The levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and catalase （CAT） were measured according to the instructions of the respective assay kits. Hematoxylin and eosin （HE） staining was used to observe pathological changes in kidney tissues. Immunohistochemistry was employed to detect the average optical density values of α-smooth muscle actin （α-SMA）， fibronectin （FN）， desmin， and nephrin. Western blot analysis was used to measure the expression levels of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， RAGE， SIRT1， Caspase-3， and FoxO1 proteins in kidney tissues of DKD rats. ResultCompared with the blank control group， the model group showed significantly lower levels of SOD， GSH-Px， and CAT， and significantly higher levels of MDA （P<0.01）. The rats exhibited severe kidney damage. The positive expression of podocyte marker proteins α-SMA， FN， and desmin increased significantly， while nephrin and podocin significantly decreased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 proteins were significantly elevated， while SIRT1 and FoxO1 protein levels were significantly reduced （P<0.01）. Compared with the model control group， rats in the YTK treatment groups showed significantly higher levels of SOD， GSH-Px， and CAT， and significantly lower levels of MDA in serum （P<0.01）. The degree of kidney damage was reduced to varying extents. The average optical density values of podocyte marker proteins α-SMA， FN， and desmin were significantly decreased， while nephrin and podocin significantly increased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 in kidney tissues were significantly reduced， while SIRT1 and FoxO1 expression levels significantly increased （P<0.01）. The Chinese medicine groups demonstrated a clear dose-response trend. ConclusionYTK may alleviate kidney pathological damage， reduce proteinuria， and protect kidney function in DKD rats， thereby delaying the progression of DKD by improving podocyte autophagy through the AGE-RAGE axis-mediated SIRT1 regulation of the PI3K/Akt/FoxO1 signaling pathway. Additionally， a dose-response relationship was observed in the Chinese medicine groups.

Advanced glycation end products consumption and the decline of functional capacity in patients with Parkinson's disease: Cross-sectional study

Abstract Introduction Advanced Glycation End-Products (AGEs) are a diverse group of highly reactive molecules that play a vital role in the development of neurodegenerative disorders, such as Parkinson's Disease (PD), leading to a decline in functional and cognitive capacity. The objective of this study was to assess the intake and quantification of AGEs in individuals with PD and to correlate them with their functional and cognitive abilities. Methods This was a cross-sectional study involving 20 PD patients and 20 non-PD individuals as the Control group (C). The autofluorescence reader was used to evaluate skin AGEs, while food recall was used to quantify AGEs consumed for three different days. The Montreal Cognitive Assessment, Short Physical Performance Battery, and handgrip tests were used. PD patients demonstrated greater impairment in functional capacity compared to the control group. Results Dominant Handgrip (p = 0.02) and motor performance, in the sit and stand test (p = 0.01) and Short Physical Performance Battery (SPPB) (p = 0.01) were inferior in PD patients than the control group. Although PD patients tended to consume less AGEs than the control group, AGE intake was negatively correlated with handgrip strength in individuals with PD (r = -0.59; p < 0.05). Conclusion PD patients had lower strength and functional capacity, suggesting that the effects of AGEs might be exacerbated during chronic diseases like Parkinson's.

Presence of circulatory autoantibodies against glycated histones in diabetic patient in Saudi Arabia

Background: Advanced glycation end products (AGEs) in diabetic patients can trigger several autoimmune responses. This article aims to assess the presence of circulating autoantibodies against glycated histones and their role in complications in diabetic patients in the Saudi population. Methods: A total of one hundred twenty samples were collected from diabetic patients with different age groups and healthy individuals as control. All serum samples were collected from Prince Sultan Military Medical City (PSMMC) in Riyadh City in Saudi Arabia. Glycated H2A was prepared and characterized using different physiochemical techniques. Then, ELISA was performed to assess the presence of circulating autoantibodies against glycated histones in diabetic patients’ samples compared with control healthy individuals in the Saudi population. Results: The glycation of H2A under our experimental conditions appears to be completed in 14 days. also, our data showed high circulating autoantibodies were detected against glycated H2A in all diabetic patients’ plasma with different dilutions. Remarkably, diabetic patients’ group 1 (under 20 years old group) showed highly significant binding activity values in each dilution. However, diabetic patients in groups 2 and 3 showed less binding but still significant values when compared to control healthy individuals. Conclusions: This finding provides novel perspectives into existing of circulating autoantibodies against glycated histones in diabetes patients in Saudi Arabia. Therefore, these circulating autoantibodies might be used as valuable tools for understanding the glycation mechanisms in diabetic patients in addition to providing diagnostic and prognostic knowledge. However, their roles in diabetic complications need further investigation.

Síntesis de glicoconjugados de albúmina sérica bovina y oligosacáridos de quitosano para el análisis de adhesión bacteriana / Synthesis of glycoconjugates of bovine albumin and chitosan oligosaccharides for the analysis of bacterial adhesion / Síntese de glicoconjugados de albumina serica bovina e oligossacarídeos de quitosana para análise de adesão bacteriana

Resumen El aumento de la resistencia a los antibióticos por parte de bacterias patógenas ha motivado la búsqueda de alternativas para disminuir su utilización. Dentro de las opciones propuestas se encuentra la terapia de antiadherencia, en la cual se utilizan moléculas análogas a los glicoepítopes que son reconocidos por las bacterias para impedir la unión de éstas al tejido celular. En este estudio se llevó a cabo la obtención de glicoconjugados por medio de la reacción de Maillard partiendo de albúmina sérica bovina (BSA) y oligosacáridos de quitosano (oligosacáridos sin ultrafiltrar, ultrafiltrados y ultrafiltrados acetilados), en proporción 1:1 (p/p) a tres temperaturas de incubación (50, 60 y 70 °C) por 30 min. La caracterización de los conjugados sintetizados se realizó utilizando electroforesis (SDS-PAGE), espectroscopía de infrarrojo y espectroscopía de fluorescencia. Se realizaron ensayos de reconocimiento usando aglutinina de germen de trigo (WGA) y bacterias [Escherichia coli (K88ac y K88+)]. La caracterización por medio de electroforesis y espectroscopía de infrarrojo evidenció la unión de los oligosacáridos de quitosano a la estructura de la BSA. Además, los ensayos evidenciaron el reconocimiento de las moléculas sintetizadas tanto por la lectina WGA como por las bacterias. Los glicoconjugados sintetizados sin ultrafiltrar ni acetilar mostraron resultados muy favorables en el reconocimiento por ambas bacterias, lo que constituye una ventaja práctica, ya que su implementación a mayor escala reduciría costos de producción

Abstract The increase in antibiotic resistance by pathogenic bacteria has motivated the search for alternatives to reduce the use of antibiotics. Among these alternatives is anti-adhesion therapy, in which molecules that mimic the glycoepitopes that recognise bacteria are used to prevent their binding to cellular tissue. In this study, glycoconjugates were obtained by means of the Maillard reaction starting from bovine serum albumin (BSA) and chitosan oligosaccharides (unfiltered oligosaccharides, ultrafiltered and acetylated ultrafiltered), in a ratio of 1:1 (w/w) at three incubation temperatures (50, 60 and 70 °C) per 30 min. The characterisation was performed using the techniques of electrophoresis (SDS-PAGE), infrared spectroscopy and fluorescence spectroscopy. Recognition assays were performed using wheat germ agglutinin (WGA) and Escherichia coli bacteria (K88ac and K88+). Characterisation by electrophoresis and infrared spectroscopy demonstrated the binding of chitosan oligosaccharides to the structure of BSA. In addition, the tests showed the recognition of the molecules synthesised by both the WGA lectin and the E. coli bacteria. The glycoconjugates synthesised without ultrafiltration or acetylation showed very favourable results in recognition with both bacteria, which is an advantage, since its implementation on a larger scale would reduce production costs.

Resumo O aumento da resistência aos antibióticos por bactérias patogênicas tem motivado a busca de alterna­tivas para reduzir seu uso. Entre essas alternativas está a terapia anti-adesão, na qual são utilizadas moléculas análogas aos glicoepítopos que são reconhecidas pelas bactérias para impedir sua união ao tecido celular. Neste estudo, os glicoconjugados foram obtidos por meio da reação de Maillard a partir de albumina sérica bovina (BSA) e oligossacarídeos de quitosana (oligossacarídeos não ultra­filtrados, ultrafiltrados e acetilados ultrafiltrados), na proporção de 1:1 (p/p) em três temperaturas de incubação (50, 60 e 70 °C) durante 30 min. A caracterização dos conjugados sintetizados foi realizada utilizando a eletroforese (SDS-PAGE), espectroscopia de infravermelho e espectroscopia de fluorescência. Os ensaios de reconhecimento foram realizados utilizando aglutinina de germe de trigo (WGA) e bactérias [Escherichia coli (K88ac e K88+)]. A caracterização por meio de eletroforese e espectroscopia de infravermelho demonstrou a união dos oligossacarídeos de quitosana à estrutura da BSA. Além disso, os testes evidenciaram o reconhecimento das moléculas sintetizadas tanto pela lectina WGA quanto pelas bactérias. Os glicoconjugados sintetizados sem ultrafiltração ou acetilação apresentaram resultados muito favoráveis no reconhecimento por ambas as bactérias, o que é uma vantagem, visto que sua implementação em maior escala reduziria custos de produção.

Oxidative stress and antioxidant markers in patients with alopecia areata: A comparative cross-sectional study

Background: Alopecia areata is a chronic inflammatory skin disease. Oxidative stress may contribute to the pathogenesis of this condition. Aim: To evaluate the serum oxidative stress markers and antioxidant capacity in patients with alopecia areata. Methods: This cross-sectional study was performed on 40 patients with alopecia areata and 40 healthy controls. The fasting blood sugar, C-reactive protein, lipid profile, and serum oxidative markers, including advanced glycation end products and advanced oxidation protein products, were measured in this study. Also, antioxidant enzymes, including paraoxonase-1, lecithin-cholesterol acyltransferase and serum ferric-reducing antioxidant power, were determined. Results: The serum levels of advanced glycation end products and advanced oxidation protein products were significantly higher in patients with alopecia areata, compared to the controls (P < 0.001), whereas the levels of ferric-reducing antioxidant power, paraoxonase-1 and lecithin-cholesterol acyltransferase were significantly lower in patients with alopecia areata, compared to the controls (P < 0.001). The mean fasting blood sugar level was significantly higher in patients with alopecia areata, compared to the controls. The ferric reducing antioxidant power level was significantly associated with the percentage of hair loss (P = 0.01, r = 0.4) and the serum C-reactive protein level (P = 0.03, r = –0.3) in patients with alopecia areata. Limitations: Since the current study had a cross-sectional design, no cause-effect relationship was established between alopecia areata and oxidative stress. The sample size of our study was also small. Conclusion: Based on the present results, the oxidant-antioxidant enzymatic system is impaired in alopecia areata due to the increased oxidative products and decreased antioxidant activity

Evaluation of Dry Fasting Effect during Ramadan on Protein Glycation in Saudi Individuals

Introduction: The non-enzymatic protein glycation alters protein function and contributes to many biochemical disorders. The accumulation of advanced glycation end-products (AGEs) is associated with the complications of diabetes, kidney disease, metabolic disorders and degenerative diseases. Objectives: This study was designed to measure the level of some glycated proteins such as glycated insulin and glycated hemoglobin in Saudi volunteers before and after dry fasting in Ramadan. Methods: Blood samples were collected twice; first sample (before) and second sample (after) dry fasting. The study included 45 Saudi male volunteers, whose ages ranged between23 and 52 years They were divided into four groups: healthy, type II diabetic patients, smokers, and obese individuals. Plasma glucose level and HbA1c were measured immediately using (Beckman coulter). Assessment of insulin resistance was determined using the equation of homeostasis model for insulin resistance (HOMA-IR). Plasma insulin level and glycated ins lin % were assayed by TSQ Vantage Triple Stage Quadruple LC/MS Mass Spectrometer from Thermo Scientific. Results: Level of HbA1c, HOMA IR and glycated insulin in healthy, type II diabetic patients, smokers, and obese individuals showed significant decrease in the second sample. The level of HbA1c showed a significant decrease (p-value <0.0001) after dry fasting (5.69 � 1.55 %), (6.14 � 1.77%). The level of HOMA IR showed significant decrease (p-value <0.0001) after dry fasting (1.97 � 1), (2.46 � 1.28). The level of glycated insulin showed significant decrease (p-value <0.0001) after dry fasting (6.25 � 2%), (7.71 � 2.48%). Conclusion: Glucose, HbA1c, HOMA IR, and glycated insulin levels showed a significant decrease after dry fasting. Reduced protein glycation and formation of advanced glycation end products, can improve the clinical course of many medical disorders. More researches are needed to understand the molecular mechanisms behind glycation-induced clinical disorders and diseases, as well as to crrelate these mechanisms to the diagnosis and prevention of lifestyle-related diseases

Changes of RAGE/p38MAPK/NF-κB signaling pathway in brain tissue of subchronic fluorosis rats and protective effects of Ginkgo biloba extract and RAGE antagonist / 环境与职业医学

Background Fluorine accumulates in the brain tissue after long-term excessive intake and subsequently cause nerve damage and decline of learning and memory ability. Receptor of advanced glycation end-products (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway is considered to be involved in the associated mechanism. Objective To study the changes of RAGE/ p38MAPK/ NF-κB signaling pathway in rats with subchronic fluorosis, and to explore the protective effects of extract of Ginkgo biloba 761 (EGb761) and RAGE antagonist (FPS-ZM1) on neuromemory ability. Methods Ninety male clean SD rats were divided into 9 groups with 10 rats in each group. The modeling period was 6 months. Control group (C group): free drinking tap water (fluoride content <0.5 mg·L−1), low- and high-dose fluoride groups (LF group, HF group): free drinking tap water with 10 or 50 mg·L−1 fluoride; intervention group of Ginkgo biloba extract (CE, LFE, and HFE groups): on the basis of the C group, LF group, and HF group, 100 mg·kg−1·d−1 EGb761 was given daily via intragastric administration; FPS-ZM1 intervention groups (CF, LFF, and HFF groups): 7 d before the end of modeling, 1 mg·kg−1·d−1 FPS-ZM1 was injected intraperitoneally daily on the basis of the C group, LF group, and HF group. The contents of fluoride in brain and blood of each group were detected. The learning and memory ability was tested by water maze experiment. The histopathologic changes of the hippocampus were detected by Nissl staining. The protein expression levels of RAGE and its ligand high mobility group protein B1 (HMGB1), NF-κB, p38MAPK, phospho-p38MAPK (p-p38MAPK), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in brain tissue were detected by Western blotting. The mRNA expression levels of RAGE, HMGB1, and p38MAPK were detected by quantitative real-time PCR. Results Compared with the C group, the contents of blood fluoride and brain fluoride in the LF and the HF groups were increased (P<0.05). The results of the water maze experiment showed that, compared with the C group, the escape latency time of the LF group and the HF group was longer and the crossing times were reduced; compared with the HF group, the escape latency time of the HFE group and the HFF group was shortened, and the crossing times were increased (P<0.05). The Nissl staining results showed that the number of Nissl body in the HF group decreased compared with the C group; compared with the HF group, the number of Nissl body in the HFE group and the HFF group increased. The Western blotting results showed that compared with the relative protein expression levels of RAGE, HMGB1, NF-κB, p38MAPK, p-p38MAPK, IL-6, and TNF-α in the C group , the levels of above indicators in the HF group and the levels of RAGE, HMGB1, NF-κB, p-p38MAPK, and IL-6 in the LF group were up-regulated (P<0.05); compared with the HF group, the levels of above indicators in the HFE group and the HFF group were all down-regulated (P<0.05); compared with the relative protein expression levels of RAGE and HMGB1 in the LF group, the levels in the LFE group and the LFF group were all down-regulated (P<0.05). The quantitative real-time PCR results showed that compared with the C group, the mRNA expression levels of RAGE and HMGB1 in the LF group and the HF group were up-regulated; compared with the LF group, the mRNA expression levels of RAGE in the LFE group and the LFF group were down-regulated ; compared with the HF group, the mRNA expression levels of RAGE and HMGB1 in the HFE group and the HFF group were down-regulated (P<0.05). Conclusion The central nervous system injury caused by subchronic fluorosis may be related to the activation of RAGE/p38-MAPK/NF-κB signaling pathway, which can impair the learning and memory ability of rats, while EGb761 and FPS-ZM1 may have certain protective effects on the nerve injury.

Mechanism of Yitangkang in Improving Apoptosis of Skeletal Muscle Cells by Inhibiting AGE/RAGE Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance （IR） by inhibiting the advanced glycation end product （AGE）/receptor for the advanced glycation end product （RAGE） signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group， a model group， high-， medium-， and low-dose Yitangkang-medicated serum groups （40， 20， and 10 g·kg-1）， and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted，the cell viability and glucose consumption level of each group were determined. In addition，the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， p53， cysteinyl aspartate-specific protease-3 （Caspase-3）， and cysteinyl aspartate-specific protease-9 （Caspase-9）］ were determined using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group， a model group， high-，medium-，and low-dose Yitangkang groups （40， 20， and 10 g·kg-1）， and a western medicine group （pioglitazone hydrochloride，1.35 mg·kg-1）. The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin （STZ） in animals and verified by the hyperinsulinemic-euglycemic clamp （HEC） test. After the model was determined successfully， the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group，while Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2， Bax， p53， Caspase-3， and Caspase-9. Result① In vitro experiments. compared with the blank group， the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group （P<0.01）. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. The medium-dose Yitangkang showed a similar effect as RAGE inhibitor， and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.

Effect of Jingui Shenqiwan on Diabetic Osteoporosis in Mice via AGEs/RANKL/NF-κB Pathway Based on Theory of "Kidneys Governing Bones" / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Jingui Shenqiwan on diabetic osteoporosis （DOP） in mice by regulating the advanced glycation end products （AGEs）/receptor activator of nuclear factor-κB ligand （RANKL）/nuclear factor-κB （NF-κB） signaling pathway based on the theory of "kidneys governing bones". MethodForty 6-week-old male and female skeletal-muscle-specific， dominant negative insulin-like growth factor-1 receptor （MKR） mice were selected and fed on a high-fat diet for eight weeks to establish the DOP model. The model mice were randomly divided into a model group， low- and high-dose Jingui Shenqiwan group （1.3， 2.6 g·kg-1）， and an alendronate sodium group （0.01 g·kg-1）， with 10 mice in each group. Additionally， 10 FVB/N mice of the same age were assigned to the normal group. The corresponding drugs were administered orally to each group once a day for four weeks. After the administration period， fasting blood glucose （FBG） measurement and oral glucose tolerance test （OGTT） were conducted. Kidney function and kidney index were measured. Renal tissue pathological changes were observed through hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to assess the protein expression levels of AGEs， phosphorylated NF-κB （p-NF-κB）， and RANKL in renal tissues. Western blot analysis was conducted to measure the expression of proteins related to the AGEs/RANKL/NF-κB signaling pathway， osteoprotegerin （OPG）， and Runt-related transcription factor 2 （RUNX2） proteins in femoral bone tissues. ResultCompared with the normal group， mice in the model group exhibited significantly increased FBG （P<0.01）， trabecular bone degeneration， abnormal bone morphological parameters， significantly increased area under the curve （AUC） of OGTT （P<0.01）， enlarged kidney volume， significantly increased kidney function indicators and kidney index （P<0.01）， disrupted renal glomeruli and renal tubule structures， significantly increased expression of AGEs， RANKL， and p-NF-κB/NF-κB in renal tissues （P<0.05）， and significantly decreased expression of OPG and RUNX2 in femoral bone tissues （P<0.01）. Compared with the model group， mice in the Jingui Shenqiwan groups showed a significant decrease in OGTT AUC （P<0.01）. Histopathological analysis revealed alleviated structural lesions in renal glomeruli and renal tubules. Furthermore， the expression of AGEs， RANKL， and p-NF-κB/NF-κB in renal tissues was significantly reduced （P<0.05， P<0.01）， and the expression of RUNX2 and OPG in femoral bone tissues was significantly increased （P<0.05， P<0.01）. ConclusionJingui Shenqiwan can improve kidney function and downregulate the AGEs/RANKL/NF-κB signaling pathway to inhibit inflammatory reactions， thereby alleviating the symptoms of DOP in mice， demonstrating a therapeutic effect on DOP from the perspective of the kidney.

Effect of Modified Erchentang on Bronchioles of Rats with Chronic Obstructive Pulmonary Disease by HMGB1/RAGE/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect of modified Erchentang on the expression of key molecules in the high mobility group Box 1 protein （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-κB （NF-κB） signaling pathway in bronchioles of rats with chronic obstructive pulmonary disease （COPD）， to explore the mechanism of modified Erchentang against bronchiolar inflammation of COPD rats via HMGB1/RAGE/NF-κB signaling pathway. MethodSixty SD rats were randomly divided into normal group， model group， modified Erchentang low-， medium- and high-dose groups （5， 10， 20 g·kg-1·d-1） and ethyl pyruvate （HMGB1 inhibitor） group， with 10 in each group. The COPD rat model was prepared by cigarette smoke combined with tracheal injection of lipopolysaccharide （LPS）. After modeling， the modified Erchentang groups were given corresponding drugs （ig） and Ringer's solution （4 mL， ip）， while the EP group was treated with equal volume of normal saline （ig） and EP （0.04 g·kg-1·d-1， ip）. The normal group and the model group received equal volume of normal saline （ig） and Ringer's solution （ip） for 21 consecutive days. The contents of HMGB1， chemokine （C-X-C motif） ligand 1 （CXCL1）， CXCL2 and monocyte chemotactic protein-1 （MCP-1） in bronchoalveolar lavage fluid （BALF） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expressions of HMGB1， RAGE and NF-κB p65 were determined by Real-time polymerase chain reaction （Real-time PCR）， and the protein expressions of HMGB1， RAGE， p-NF-κB p65， and alpha-smooth muscle actin （α-SMA） in bronchioles tissue of rats were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the forced vital capacity （FVC）， forced expiratory volume in the first second （FEV1） and FEV1/FVC in the model group were decreased （P<0.01） while the contents of HMGB1， CXCL1， CXCL2 and MCP-1 in BALF were increased （P<0.01）. And the model group presented higher mRNA expressions of HMGB1， RAGE and NF-κB p65 （P<0.01） and protein expressions of HMGB1， RAGE， p-NF-κB p65 and α-SMA （P<0.05， P<0.01） than the normal group. Compared with the model group， the modified Erchentang medium- and high-dose groups had increased FEV1/FVC （P<0.05， P<0.01）， lowered contents of HMGB1， CXCL1， CXCL2 and MCP-1 in BALF （P<0.05， P<0.05）， and reduced mRNA expressions of HMGB1， RAGE and NF-κB p65 （P<0.05， P<0.01） and protein expressions of HMGB1， RAGE， p-NF-κB p65 and α-SMA （P<0.05， P<0.01）. ConclusionModified Erchentang can resist bronchiolar inflammation of COPD rats. The mechanism may be related to down-regulating the mRNA expressiona of HMGB1 and RAGE， inhibiting the activity of NF-κB， and reducing the release of HMGB1， CXCL1， CXCL2 and MCP-1， thus suppressing the inflammatory injury and abnormal repair of bronchioles.

The mechanism of the receptors for advanced glycation end products affecting pericyte detachment from blood vessels after traumatic brain injury / 西安交通大学学报(医学版)

【Objective】 To observe the reactive change of cortical perivascular cells after craniocerebral injury and explore its mechanism. 【Methods】 The controllable cortical impact animal model was used to simulate craniocerebral injury, the expressions of cortical pericyte markers at different time points after trauma were studied by Western blotting, and the biological behavior of vascular pericytes after craniocerebral injury was determined by transmission electron microscopy. Post-traumatic high mobility group box 1 (HMGB1), receptor for advanced glycation end product (RAGE), and nuclear factor κB (NF-κB) were detected by Western blotting. The experimental animals were divided into FPS-ZM1 (a specific RAGE receptor blocker) injection group and wild-type group. Wet and dry brain weight and transmission electron microscopy were used to study the post-traumatic effects of HMGB1-RAGE on pericytes. The primary mouse brain microvascular pericytes were cultured and supplemented with HMGB1 recombinant protein; the cultured pericytes supplemented with FPS-ZM1 were used as the control to explore the effect of HMGB1-RAGE pathway on vascular pericytes in vitro. 【Results】 The expression levels of early post-traumatic cortical pericyte markers platelet-derived growth factor receptor beta (PDGFR-β) and NG2 proteoglycan (NG2) decreased (PDGFR-β, Control vs. CCI 3D P<0.05; NG2, Control vs. CCI 6H P<0.05; Control vs. CCI 1D P<0.05). We found that pericytes were detached from blood vessels, accompanied by local blood-brain barrier opening. The expression of HMGB1-RAGE-NF-κB signaling pathway was increased in the early cortex after trauma (HMGB1, Control vs. CCI 6H P<0.05, Control vs. CCI 1D P<0.05; RAGE, Control vs. CCI 6H P<0.05, Control vs. CCI 1D P<0.05, Control vs. CCI 3D P<0.05, Control vs. CCI 5D P<0.05, Control vs. CCI 7D P<0.05; NF-κB, Control vs. CCI 6H P<0.05, Control vs. CCI 1D P<0.05). After blocking the binding of RAGE with the ligand, cortical edema was reduced (CCI 6H P<0.05, CCI 1D P<0.05), and neurovascular unit damage was reduced. HMGB1 recombinant protein could increase the migration ability of cultured pericytes (Control vs. HMGB1 P<0.05, Control vs. HMGB1+FPS-ZM1 P<0.05), and could be reversed by FPS-ZM1 (HMGB1 vs. HMGB1+FPS-ZM1 P<0.05). 【Conclusion】 High-level HMGB1 after traumatic brain injury mediates pericytes’ detachment from blood vessels through RAGE on pericytes and leads to the occurrence of local cerebral edema.

Dahuang Mudantang Alleviates Intestinal Injury in Rat Model of Acute Pancreatitis by Regulating HMGB1/RAGE/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Dahuang Mudantang in alleviating the intestinal injury in the rat model of acute pancreatitis via the high-mobility group box 1 （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-κB （NF-κB） signaling pathway. MethodOne hundred and twenty SPF-grade Wistar rats received retrograde injection of 5% sodium taurocholate into the biliopancreatic duct for the modeling of intestinal injury in acute pancreatitis. The rats were randomized into blank， model， low-， medium-， and high-dose （3.5， 7， 14 g·kg-1， administrated by gavage） Dahuang Mudantang， and octreotide （1×10-5 g·kg-1， subcutaneous injection） groups （n=20）. The rats in blank and model groups received equal volume of distilled water by gavage. Drugs were administered 1 h before and every 12 h after modeling， and samples were collected 24 h after modeling. The general status of the rats was observed. The biochemical methods were employed to measure the levels of amylase （AMS） and C-reactive protein （CRP） in the serum. The enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6 in the colon tissue. The morphological changes of pancreatic and colon tissues were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to measure the expression levels of HMGB1， RAGE， inhibitor of NF-κB kinase （IKK）， and NF-κB suppressor protein α（IκBα）in the colon tissue. ResultThe rats in the model group showed poor general survival， writhing response， reduced frequency of defecation， and dry stool. The symptoms of rats in the model group were mitigated in each treatment group， and the high-dose Dahuang Mudantang showed the most significant effect. Compared with the normal group， the model group had elevated AMS and CRP levels （P<0.05）， which were lowered by Dahuang Mudantang （P<0.05）， especially that at the high dose （P<0.05）. Compared with the normal group， the modeling elevated that levels of TNF-α， IL-1β， and IL-6 （P<0.05）. Such elevations were lowered by Dahuang Mudantang （P<0.05）， and the high-dose group and the octreotide group showed better performance （P<0.05）. The modeling caused necrotic， congested， and destructed pancreatic and colonic tissues， which were ameliorated by the drugs， especially high-dose Dahuang Mudantang. Compared with the normal group， the modeling up-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）. Compared with the model group， Dahuang Mudantang and octreotide down-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）， and the high-dose Dahuang Mudantang demonstrated the best performance （P<0.05）. Western blot results showed a trend consistent with the results of Real-time PCR. ConclusionDahuang Mudantang can improved the general status， reduce inflammation， and alleviate histopathological changes in the pancreatic and colon tissues in the rat model of acute pancreatitis by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.

Improvement effects and its mechanism of catalpol on testicular lesions in KK-Ay spontaneous diabetic mice by regulating glycolysis / 中国药房

OBJECTIVE To study the improvement effects and its mechanism of catalpol on testicular lesions in KK-Ay spontaneous diabetic mice on the basis of glycolysis process mediated by advanced glycation end products （AGEs） and their receptors （RAGE）. METHODS KK-Ay spontaneous diabetic mice fed with high-fat diet were used as diabetic model， and then randomly divided into model group， catalpol group （100 mg/kg）， aminoguanidine group （AGEs inhibitor， 100 mg/kg） and FPS- ZM1 group （RAGE inhibitor， 1 mg/kg）， and C57BL/6J mice fed in the same period were set as normal group， with 6 mice in each group. The catalpol group and aminoguanidine group mice were given relevant medicine intragastrically， normal group and model group mice were given constant volume of normal saline intragastrically， and FPS-ZM1 group mice were given relevant medicine 1 mL/g intraperitoneally， for consecutive 8 weeks. After the last administration， the body mass， fasting blood glucose， 24-hour food intake， water consumption， urine volume， testicular organ coefficient， and sperm motility of the mice were measured； pathological morphology and ultrastructural structure of testicular tissue were observed； the levels of reduced glutathione （GSH）， superoxide dismutase （SOD）， lactate dehydrogenase （LDH） and sugar metabolites in testicular tissue of mice were detected； pathway enrichment analysis was performed； the level of AGEs in serum and testicular tissue， protein expressions of RAGE， B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）， and mRNA expressions of key rate-limiting enzymes [hexokinase （HK）， phosphofructose kinase （PFK）， pyruvate kinase （PK）， LDH] in testicular tissue were alldetected. RESULT S Catalpol could significantly improve the general symptoms， testicular organ coefficients and motility ofsperm in KK-Ay spontaneous diabetic mice （P＜0.05 or P＜0.01）. The morphology and ultrastructure of spermatogenic cells in each layer of the seminiferous tubules were all improved. The levels of GSH， SOD and LDH in testicular tissue，the levels of the metabolic product glucose fructose-1，6-diphosphate， 3-phosphate glycerate， 3-phosphate glyceraldehyde， lactic acid and pyruvate， the expressions of HK， PFK， PK and LDH mRNA were all significantly increased（P＜0.05 or P＜0.01）； the levels of AGEs in serum and testicular tissue， the expression of RAGE protein and the ratio of Bax to Bcl-2 in testicular tissue were significantly decreased（P＜0.05 or P＜0.01）. Aminoguanidine and FPS-ZM1 could significantly improve the levels of most of above indicators in mice（P＜0.05 or P＜0.01）. CONCLUSIONS Catalpol shows significant improvement effects on testicular lesions of KK-Ay spontaneous diabetic mice， and its mechanism of action was associated with upregulation of AGEs/RAGE signaling pathway- mediated glycolysis.

Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo.@*METHODS@#Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- β (Aβ), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.@*RESULTS@#Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01).@*CONCLUSION@#EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.

Risk factors of lung injury and pulmonary hypertension in patients with chronic obstructive pulmonary disease and the predictive value of serum SDF-1 and sRAGE / 实用医学杂志

Objective To analyze the risk factors for lung injury and pulmonary arterial hypertension in patients with chronic obstructive pulmonary disease(COPD),and the predictive value of serum SDF-1 and sRAGE for lung injury and pulmonary arterial hypertension.Methods A total of 200 patients with COPD admitted to our hospital from January 2021 to January 2023 were selected as research objects,23 of whom occurred lung injury and the rest 177 had no lung injury,and 31 developed pulmonary hypertension and the remaining 169 had no pulmonary hypertension.The predictive value of serum SDF-1 and sRAGE for pulmonary injury and pulmonary hypertension was analyzed.Results Multi-factor logistic regression analysis showed that D-D,PCT,CRP,RDW,MPV,PLT,NLR,SDF-1,sRAGE,pulmonary hypertension,arterial blood oxygen partial pressure,FVC and FEV1 were the main factors affecting lung injury in patients with COPD.D-D,PCT,CRP,RDW,MPV,PLT,NLR,SDF-1,sRAGE,arterial partial oxygen pressure,FVC,FEV1 and CT angiographic pulmonary artery volume were the main factors affecting the occurrence of pulmonary hypertension in those patients(P<0.05).Serum SDF-1 and sRAGE were positively correlated with lung injury and pulmonary hypertension in patients with COPD(P<0.05).The sensitivity and accuracy of SDF-1 and sRAGE for predicting lung injury and pulmonary hyperten-sion in patients with COPD were higher than those of SDF-1 and SRage alone(P<0.05).Conclusions Pulmonary injury in patients with COPD is associated with D-D,PCT,CRP,RDW,MPV,PLT,NLR,SDF-1,sRAGE,pulmonary hypertension,arterial blood oxygen partial pressure,FVC,FEV1.The occurrence of pulmonary hyper-tension is related to D-D,PCT,CRP,RDW,MPV,PLT,NLR,SDF-1,sRAGE,arterial partial pressure of oxy-gen,FVC,FEV1 and CT angiography of pulmonary artery volume.Combined detection of SDF-1 and sRAGE has a higher predictive value for lung injury and pulmonary hypertension.