Effect of Sarcopenia on 10-Year Risk of Atherosclerotic Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM). Methods: This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression. Results: The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model. Conclusion: This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.

Correlation between fat-to-muscle mass ratio and cognitive impairment in elderly patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Fat to muscle mass ratio (FMR), a novel index integrating fat and muscle composition, has garnered attention in age-related conditions such as type 2 diabetes mellitus (T2DM) and neurodegenerative diseases. Despite this research on the relationship between FMR and cognitive impairment (CI) in T2DM remains scarce. This study aimed to investigate the sex-specific association between FMR and CI in elderly T2DM patients. METHODS: A total of 768 elderly (> 60 years) T2DM in-patients (356 men and 412 women) were recruited from the Department of Endocrinology at Tianjin Nankai University affiliated hospital. Bioelectrical Impedance Analysis (BIA) was used to assess body composition, and Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive performance. T2DM patients were categorized into normal cognitive function (NC) and cognitive impairment (CI) groups based on MoCA scores and stratified by sex. Binary logistic regression was employed to examine the association between FMR and CI. RESULTS: Among the participants, 42.7% of men and 56.3% of women experienced cognitive deterioration. Women with CI exhibited lower body mass index (BMI) and skeletal muscle mass index (SMI), while men with cognitive disorders showed lower SMI, FMR, and higher fat mass index (FMI). FMR was consistently unrelated to cognition in females, irrespective of adjustment made. However, in males, FMR was significantly associated with an increasing risk of cognitive dysfunction after adjusting for demographic and clinical variables (OR: 1.175, 95% CI: 1.045-1.320, p = 0.007). Furthermore, for each 0.1 increase in FMR, the incidence of CI rose by 31.1% after additional adjustment for BMI. In males, the prevalence of CI increased sequentially across FMR quartiles (p < 0.05). CONCLUSION: Elderly T2DM men with high FMR had unfavorable cognitive function. FMR is independently associated with an increased risk of CI in male T2DM patients regardless of BMI.

Risk factors for cognitive impairment in middle-aged type 2 diabetic patients: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate risk factors for cognitive impairment (CI) and explore the relationship between obesity and cognition in hospitalised middle-aged patients with type 2 diabetes (T2DM). METHODS: Subjects were divided into normal cognitive function (NCF) (n=320) and CI (n=204) groups based on the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The risk factors for CI were determined by logistic regression analysis and generalised linear modelling. The associations between obesity parameters (body mass index (BMI) and waist circumference (WC)) and cognitive ability were studied with the use of linear regression analysis, piecewise regression modelling and interaction analysis. The receiver operating characteristic curve analysis was used to examine the diagnostic value of influencing factors for cc RESULTS: The prevalence of CI was 38.9% in hospitalised middle-aged T2DM patients (median age, 58 years). Age, WC, hypoglycaemic episode within past 3 months and cerebrovascular disease (CVD) were identified as independent risk factors for CI, while the independent protective factors were education, diabetic dietary pattern, overweight and obesity. BMI was a protective factor for the MoCA score within a certain range, whereas WC was a risk factor for the MMSE and MoCA scores. The area under the curve for the combination of BMI and WC was 0.754 (p<0.001). CONCLUSION: Age, education, diabetic dietary pattern, WC, overweight, obesity, hypoglycaemic episode in 3 months and CVD may be potential influencing factors for the occurrence of CI in hospitalised middle-aged population with T2DM. The combination of BMI and WC may represent a good predictor for early screening of CI in this population. Nevertheless, more relevant prospective studies are still needed.

Probabilistic Risk Assessment of Heavy Metals in Mining Soils Based on Fractions: A Case Study in Southern Shaanxi, China.

With rapid economic development, soil heavy metal (HM) pollution has emerged as a global environmental concern. Because the toxicity of HMs differs dramatically among various fractions, risk assessments based on these fractions are of great significance for environmental management. This study employed a modified Hakanson index approach to evaluate the possible ecological impacts of soil HMs in a gold mine tailings pond in Shaanxi Province, China. A modified Hakanson-Monte Carlo model was built to perform a probabilistic risk assessment. The results showed that: (1) the exceedance rates of chromium (Cr) and zinc (Zn) were 68.75% and 93.75%, respectively. Moreover, the overall concentrations of nickel (Ni), copper (Cu), arsenic (As), and lead (Pb) were higher than the background soil environmental values in China. (2) HMs with the lowest oxidizable fraction were mostly present in the residual fraction. The oxidizable portions of Cr, Cu, and Pb and the reducible and residual fractions of As were notably distinct. (3) The risk degrees of Cr, Ni, Cu, and Zn were low; those of As and Pb were very high and moderate; and the comprehensive ecological hazard index was very high. This study offers a solid scientific foundation for ecological risk notification and environmental management.

Characteristics of Soil Arsenic Contamination and the Potential of Pioneer Plants for Arsenic Remediation in Gold Mine Tailings.

Arsenic (As) contamination of gold mine tailings poses major threats to the natural environment and human health, necessitating adequate management measures. To investigate the soil As contamination level and the potential of pioneer plants for As remediation, the soil and plants of an abandoned gold mine tailings in the Qinling Mountains were analyzed. The level of As contamination was assessed using the single-factor pollution index and potential ecological risk index, and its bioeffectiveness was analyzed. The enrichment capability of plants was investigated using the bioaccumulation factor and translocation factor. Redundancy analysis and partial least squares regression were employed to investigate factors affecting the distribution of As in soil and plants. The results show that As in soil mainly existed in the difficult-available state, with serious contamination and extremely high ecological risk. Lythrum salicaria L. and Equisetum ramosissimum Desf. are the preferred plants for remediation of As contamination through screening pioneer plants. Soil total nitrogen (STN) and available phosphorus (SAP) are the main factors influencing the characteristics of As distribution in the soil. Soil available potassium (SAK), water content (SWC), and SAP promote the accumulation of As by plants. This study provides plant materials and new ideas for mine ecological remediation.

Relationships Between Body Composition and Cognitive Impairment in Hospitalised Middle-Aged Type 2 Diabetic Patients.

Objective: The aim of this study was to elucidate the relationship between specific body composition and the risk of Cognitive Impairment (CI) in middle-aged Type 2 Diabetes Mellitus (T2DM) patients. Methods: This cross-sectional study included 504 hospitalized patients with T2DM from the Department of Endocrinology and Metabolism of the Tianjin Union Medical Center. Subjects were grouped by sex, and cognitive status was assessed using the Montreal Cognitive Assessment (MoCA). The relationship between body composition and cognitive ability was investigated with the use of linear regression analysis. The association between body composition and CI risk was determined by logistic regression analysis. Results: The prevalence of CI was 39.3% in middle-aged T2DM patients. After adjusting for age, education, marriage status, carotid atherosclerosis, cerebrovascular disease and hemoglobin, multiple linear regression analysis showed that lean mass index (LMI), body mass index (BMI) and appendicular skeletal muscle index (SMI) were significant predictors for the MoCA scores in men (p < 0.05). In addition, BMI (OR 0.913, 95% CI 0.840-0.992) and LMI (OR 0.820, 95% CI 0.682-0.916) were independent protective factors for CI in males. After adjusted for age, education, marriage status, dietary control of diabetes and cerebrovascular disease, visceral obesity (VO, OR 1.950, 95% CI 1.033-3.684) and abdominal obesity (AO, OR 2.537, 95% CI 1.191-5.403) were risk factors for CI in female patients. Conclusion: The results suggest that there may be different mechanisms underlying the relationship of body compositions and cognitive performance between middle-aged male and female patients with T2DM. In addition, our finding of potential determinants of cognitive impairment may facilitate the development of intervention programs for middle-aged type 2 diabetic patients. Nevertheless, more large prospective studies looking at cognition and changes in body composition over time are needed in the future to further support their association.

Comparison of lipid accumulation product and visceral adiposity index with traditional obesity indices in early-onset type 2 diabetes prediction: a cross-sectional study.

BACKGROUND: The purpose of the study was to compare the efficacy of two novel obesity indices, lipid accumulation product (LAP) and visceral adiposity index (VAI), with traditional obesity indices in predicting early-onset type 2 diabetes (T2DM). METHODS: In this cross-sectional study, a total of 744 participants, including 605 patients newly diagnosed with T2DM and 139 non-diabetic control subjects, were enrolled from a tertiary care hospital in Tianjin, China. Participants with T2DM were divided into two groups based on their age at diagnosis, namely early-onset T2DM (age less than 40 years, n = 154) and late-onset T2DM (age 40 years or older, n = 451). The predictive power of each obesity index was evaluated using receiver operating characteristic (ROC) curve analysis. Furthermore, binary logistic regression analysis was conducted to examine the independent relationship between LAP and VAI with early-onset T2DM risk. The relationship between novel obesity indices and the age of T2DM onset was also evaluated through correlation and multiple linear regression analysis. RESULTS: In males, LAP had the highest predictive power for early-onset T2DM with an area under the ROC curve (AUC) of 0.742 (95% CI 0.684-0.799, P < 0.001). In females, VAI had the highest AUC for early-onset T2DM with a value of 0.748 (95% CI 0.657-0.839, P < 0.001), which was superior to traditional indices. Patients in the 4th quartile of LAP and VAI had 2.257 (95% CI 1.116-4.563, P = 0.023) and 4.705 (95% CI 2.132-10.384, P < 0.001) times higher risk of T2DM before age 40, compared to those in the 1st quartile, respectively. A tenfold increase in LAP was associated with a decrease in T2DM onset age of 12.862 years in males (ß = -12.862, P < 0.001) and 6.507 years in females (ß = -6.507, P = 0.013). A similar decrease in T2DM onset age was observed for each tenfold increase in VAI in both male (ß = -15.222, P < 0.001) and female (ß = -12.511, P < 0.001) participants. CONCLUSIONS: In young Chinese individuals, LAP and VAI are recommended over traditional obesity indices for improved prediction of early-onset T2DM risk.

Periodic step polarization accelerates electron recovery by electroactive biofilms (EABs).

Relatively low rate of electron recovery is one of the factors that limit the advancement of bioelectrochemical systems. Here, new periodic polarizations were investigated with electroactive biofilms (EABs) enriched from activated sludge and Geobacter sulfurreducens biofilms. When representative anode potentials (Ea ) were applied, redox centers with midpoint potentials (Emid ) higher than Ea were identified by localized cyclic voltammetry. The electrons held by these redox centers were accessible when Ea was raised to 0.4 V (vs. Ag/AgCl). New periodic polarizations that discharge at 0.4 V recovered electrons faster than normal periodic and fixed-potential polarizations. The best-performing periodic step polarization accelerated electron recovery by 23%-24% and 12%-76% with EABs and G. sulfurreducens biofilms, respectively, compared to the fixed-potential polarization. Quantitative reverse transcription polymerase chain reaction showed an increased abundance of omcZ mRNA transcripts from G. sulfurreducens after periodic step polarization. Therefore, both the rate of energy recovery by EABs and the performance of bioelectrochemical systems can be enhanced by improving the polarization schemes.

Adsorption of Toxic Tetracycline, Thiamphenicol and Sulfamethoxazole by a Granular Activated Carbon (GAC) under Different Conditions.

Activated carbon can be applied to the treatment of wastewater loading with different types of pollutants. In this paper, a kind of activated carbon in granular form (GAC) was utilized to eliminate antibiotics from an aqueous solution, in which Tetracycline (TC), Thiamphenicol (THI), and Sulfamethoxazole (SMZ) were selected as the testing pollutants. The specific surface area, total pore volume, and micropore volume of GAC were 1059.011 m2/g, 0.625 cm3/g, and 0.488 cm3/g, respectively. The sorption capacity of GAC towards TC, THI, and SMZ was evaluated based on the adsorption kinetics and isotherm. It was found that the pseudo-second-order kinetic model described the sorption of TC, THI, and SMZ on GAC better than the pseudo-first-order kinetic model. According to the Langmuir isotherm model, the maximum adsorption capacity of GAC towards TC, THI, and SMZ was calculated to be 17.02, 30.40, and 26.77 mg/g, respectively. Thermodynamic parameters of ΔG0, ΔS0, and ΔH0 were obtained, indicating that all the sorptions were spontaneous and exothermic in nature. These results provided a knowledge base on using activated carbon to remove TC, THI, and SMZ from water.

Distribution characteristics and ecological risk assessment of heavy metals in sediments of Shahe reservoir.

Shahe Reservoir of Northern Canal Basin was selected as the study area. Nineteen surface (0~20 cm) sediment samples and three sediment core samples were collected to analyze the spatial distribution characteristics of As, Cd, Cu, Mn, Pb and Zn in the sediments. The geo-accumulation index, potential ecological risk index and risk assessment code were used to evaluate heavy metal pollution, as well as its potential risk was analyzed according to the speciation of heavy metals. Results showed that the average enrichment factors of heavy metals compared to the background value in soil of Beijing were ranked at the order as the point source pollution area > the central area of the reservoir > the downstream area of the reservoir > the Nansha River > the upstream area of the reservoir > the Beisha River, namely, 2.57 times, 2.06 times, 1.97 times, 1.95 times, 1.87 times and 1.85 times, respectively. The sediment core samples in the central area of the reservoir and the inlet of the Beisha River showed a trend of increasing firstly and then decreasing with the change of depth. Pollution assessment results showed that sediment was moderately contaminated or moderately to strongly contaminated by As, but the other heavy metals were not polluted or lightly polluted. The potential ecological risk index of all sampling sites was less than 150, showing a low ecological risk. As Cr and Cu were mainly in the speciation of residues, with low bioavailability. Although the content of Mn and Zn were low, they showed high bioavailability. Based on correlation analysis and principal component analysis, it was speculated that the sources of various heavy metal pollution in the sediment were similar, which were possibly input from the external wastewater. The heavy metals in sediment were positively related to nutrients and organic matter, indicating that all of them were mostly from the same point polluted sources.

Assessment of Soil-Heavy Metal Pollution and the Health Risks in a Mining Area from Southern Shaanxi Province, China.

Soil-heavy metal pollution in mining areas is one of the problems in the comprehensive treatment of soil environmental pollution. To explore the degree of soil-heavy metal pollution and the human health risk in mining areas, the contents of soil As, Cd, Cu, Cr, Hg, Ni, Pb, and Cr(VI) in an abandoned gold mining area were determined. The geoaccumulation index (Igeo), single-factor pollution index (SPI), Nemerow comprehensive pollution index (NCPI), potential ecological risk index (PERI), and the human health risk assessment model were used to assess the pollution degree and the risk of soil-heavy metal pollution. Finally, the assessment results were used to provide remediation guidance. The results showed that (1) the average contents of As, Cd, Cr, Cu, Hg, and Ni in the mining area exceeded the background values of the soil elements. (2) The mining area was polluted by heavy metals to different degrees and had strong potential ecological hazards. (3) The total carcinogenic risk of heavy metals exceeded the health risk standard. The main components of pollution in the mining area were As, Cd, Cr, and Hg. Results from this study are expected to play a positive role in pollution treatment and the balance between humans and ecology.

The spatial distribution characteristics of typical pathogens and nitrogen and phosphorus in the sediments of Shahe Reservoir and their relationships.

Using samples collected in Shahe Reservoir in the upper North Canal in China, this research analyzes the structure of a microorganism group in sediment and the absolute abundance of two typical pathogenic bacteria (Escherichia coli and Enterococcus), and their relationship with environmental factors including total nitrogen (TN) and total phosphorus (TP). The study of samples collected from the surface (0-20 cm) and sediment cores shows that the absolute abundance of E. coli in horizontal distribution in the sediment is highest in downstream of the reservoir and point source pollution area. In vertical distribution, the absolute gene expression level of the two pathogenic bacteria in the sediment tends to decrease with increasing depth, although its highest value at 10-30 cm depth. The relative abundance the two pathogenic bacteria is much greater in the sediment of Shahe Reservoir with the structure of horizontal groups including Clortridium sensu stricto, unclassified Anaeroineaceae, and Povalibacter, while Anaeroineaceae is much more abundant in the group structure of the vertical distribution. Pearson correlation analysis suggests positive correlation in horizontal distribution for E. coli and TN and TP (P < 0.05) and for Enterococcus and TP (P < 0.05). The results clearly show that the amount of pathogenic bacteria in the sediment in Shahe Reservoir is most likely due to water eutrophication.

Non-enzymatic sensor for determination of glucose based on PtNi nanoparticles decorated graphene.

Diabetes has become a universal epidemic in recent years. Herein, the monitoring of glucose in blood is of importance in clinical applications. In this work, PtNi alloy nanoparticles homogeneously dispersed on graphene (PtNi alloy-graphene) was synthesized as a highly effective electrode material for glucose detection. Based on the modified PtNi alloy-graphene/glass carbon (PtNi alloy-graphene/GC) electrode, it is found that the PtNi alloy-graphene/GC electrode exhibited excellent electrocatalytic performance on glucose oxidation. Furthermore, the results from amperometric current-time curve show a good linear range of 0.5-15 mM with the limit of detection of 16 uM (S/N = 3) and a high sensitivity of 24.03 uAmM-1 cm-2. On account of the good selectivity and durability, the modified electrode was successfully applied on glucose detection in blood serum samples.

Anti-ß2GPI antibodies enhance atherosclerosis in ApoE-deficient mice.

Accelerated atherosclerosis often occurs in patients with antiphospholipid syndrome (APS), and auto-antibodies to ß2 glycoprotein I (anti-ß2GPI) are confirmed as pathogenic antibodies to APS. Our previous studies have demonstrated that the conversion of mouse peritoneal macrophages into foam cells could be enhanced by co-existence of ß2GPI and anti-ß2GPI IgG, but this phenomenon has not been explored in vivo. Here, we present a mouse model to observe the effect of anti-ß2GPI IgG in the development of atherosclerosis. Male ApoE-deficient mice were intraperitoneally injected with anti-ß2GPI IgG (100 µg/mouse) and homologous control IgG (100 µg/mouse) every week for 16 weeks. Plasma lipid composition, magnetic resonance imaging (MRI) and histological staining were used to evaluate vascular inflammation, lumen stenosis and plaque stability. The results showed that the levels of total cholesterol, triglycerol and low-density lipoprotein-cholesterol in plasma were not changed in all mice fed with high-fat diet, but the level of high-density lipoprotein-cholesterol was lower and the atherosclerosis index was significantly increased in HD + anti-ß2GPI group than in other high-fat diet groups. In addition, compared with NR IgG-treated mice, anti-ß2GPI IgG-treated mice showed more lipid deposition in the carotid artery, markedly narrowed arteriolar lumen as well as higher MMP-9 expression, more macrophages and fewer collagen fibers in the aortic arch root. Furthermore, the aortic mRNA levels of TNF-α, IL-1ß, and MCP-1 were significantly increased in anti-ß2GPI IgG-treated mice. Together, these data indicate that anti-ß2GPI IgG increases vascular inflammation, aggravates atherosclerosis and promotes the formation of vulnerable plaque in ApoE-deficient mice.

Pro­atherogenic activation of A7r5 cells induced by the oxLDL/ß2GPI/anti­ß2GPI complex.

A previous study has revealed that oxidized low­density lipoprotein (oxLDL)/ß2­glycoprotein I (ß2GPI)/anti­ß2­glycoprotein I (anti­ß2GPI), an immune complex, is able to activate the Toll­like receptor 4 (TLR4)/nuclear factor κß (NF­κß) inflammatory signaling pathway in macrophages, and consequently enhance foam cell formation and the secretion of prothrombin activators. However, the effects of the oxLDL/ß2GPI/anti­ß2GPI complex on vascular smooth muscle cells have yet to be investigated. The present study investigated whether the oxLDL/ß2GPI/anti­ß2GPI complex was able to reinforce the pro­atherogenic activities of a rat thoracic aorta smooth muscle cell line (A7r5) and examined the underlying molecular mechanisms. The results revealed that the oxLDL/ß2GPI/anti­ß2GPI complex treatment significantly (P<0.05 vs. the media, oxLDL, oxLDL/ß2GPI and ß2GPI/anti­ß2GPI groups) enhanced the pro­atherogenic activation of A7r5 cells, including intracellular lipid loading, Acyl­coenzyme A cholesterol acyltransferase mRNA expression, migration, matrix metalloproteinase­9 and monocyte chemoattractant protein 1 secretion, all via TLR4. In addition, the expression of TLR4 and the phosphorylation of NF­κß p65, p38 and ERK1/2 were also upregulated in oxLDL/ß2GPI/anti­ß2GPI complex­treated A7r5 cells. Pre­treatment with TAK­242, a TLR4 inhibitor, was able to partly attenuate the oxLDL/ß2GPI/anti­ß2GPI complex­induced phosphorylation of NF­κß p65; however, it had no effect on the phosphorylation of extracellular regulated kinase 1/2 (ERK1/2) and p38. Meanwhile, the NF­κß p65 inhibitor ammonium pyrrolidinedithiocarbamate and the ERK1/2 inhibitor U0126, but not the p38 inhibitor SB203580, were able to block oxLDL/ß2GPI/anti­ß2GPI complex­induced foam cell formation and migration in A7r5 cells. Hence, it was demonstrated that the oxLDL/ß2GPI/anti­ß2GPI complex is able to enhance the lipid uptake, migration and active molecule secretion of A7r5 cells via TLR4, and finally deteriorate atherosclerosis plaques. Additionally, it was demonstrated that oxLDL/ß2GPI/anti­ß2GPI complex­induced foam cell formation and migration may be partly mediated by the TLR4/NF­κß signaling pathway and that ERK1/2 may also participate in the process.

Immune modulation of Th1, Th2, and T-reg transcriptional factors differing from cytokine levels in Schistosoma japonicum infection.

In spite of long-term integrated control programs for Schistosoma japonicum infection in China, the infection is still persistent due to its zoonotic transmission and disease severity which further complicate its control. Th1, Th2, and T-reg cells are involved in S. japonicum immunity; however, their exact roles in immunopathology of this infection are still questionable. Therefore, the monitoring of these T cell subsets' immune responses during a primary infection of S. japonicum at both transcriptional (mRNA) and protein (cytokines) levels would be essential to point out. In experimentally infected white New Zealand rabbits, mRNA expression levels of TBX2, IRF8, GATA3, STAT6, FoxP3, and MAFF were evaluated using qPCR, whereas Th1 (IFN-γ and TNF-α), Th2 (IL4 and IL13), and T-reg (IL10 and TGF-ß1) cytokines were measured by ELISA test. Those parameters were estimated at two phases: the first being 4 and 8 weeks post-infection and the second phase at 12 weeks post-infection. The infected rabbits were categorized into group1 which was treated with praziquantel after the 8th week of infection and group 2 which was left untreated. In the first stage of infection, Th1 was superior to the other types at both mRNA (TBX2 and IRF8) and protein (IFN-γ and TNF-α) levels, but at the late stage, Th2 cytokines (IL4 and IL13) were surprisingly dominated without comparable change in Th2 transcriptional level in group 1. Concisely, the evaluation of T cell transcriptional factors provided clearer evidence about T cellular roles which would be a valuable supplement to control this disease in terms of protective and therapeutic vaccinations.

Activation of mTOR is involved in anti-ß2GPI/ß2GPI-induced expression of tissue factor and IL-8 in monocytes.

Previous study has demonstrated that activation of the mammalian target of rapamycin (mTOR) pathway in endothelial cells (ECs) results in the formation of chronic vascular lesions associated with antiphospholipid syndrome (APS). In addition, it has been shown that stimulation of monocytes and ECs by antiphospholipid antibodies (aPL) leads to a prothrombotic and proinflammatory state and up-regulated expression of tissue factor (TF) and inflammatory cytokines. However, the role of mTOR in pathogenic mechanisms of APS remains largely unexplored. In the present study, we aimed to investigate whether mTOR was involved in anti-ß2GPI/ß2GPI complex-induced expression of TF and interleukin-8 (IL-8/CXCL8) in monocytes and explore the relationship among TLR4, mTOR, MAPKs and NF-κB in such a process. The results showed that treatment of anti-ß2GPI/ß2GPI or APS-IgG/ß2GPI complex could markedly induce mTOR activation as well as expression of TF and IL-8 in THP-1 cells or primary monocytes. The mTOR inhibitor rapamycin (100nM) could attenuate the elevated expression of TF and IL-8. In addition, rapamycin could also decrease the phosphorylation of p38, ERK1/2 and NF-κB p65 stimulated by anti-ß2GPI/ß2GPI or APS-IgG/ß2GPI complex, but it had no effect on JNK. Moreover, the anti-ß2GPI/ß2GPI or APS-IgG/ß2GPI complex-induced phosphorylation of mTOR in THP-1 cells was down-regulated through inhibition of p38 (10µM, SB203580) or ERK (5µM, U0126) rather than inhibition of JNK (90nM, SP600125) or NF-κB (20µM, PDTC). Finally, the mTOR activation could also be affected by exposure to TLR4 inhibitor TAK-242 (5µM). Taken together, our results indicated that mTOR was involved in regulating anti-ß2GPI/ß2GPI-induced expression of TF and IL-8 in monocytes. In addition, the inhibition of mTOR pathway might be beneficial for the prevention and treatment of aPL-mediated thrombosis and inflammation in APS patients.

[Anti-ß2GPI antibody promotes release of inflammatory and pro-thrombosis molecules from arteries in apolipoprotein E-deficient mice].

Objective To investigate the roles of anti-beta 2 glycoprotein I antibodies (anti-ß2GPI Ab) in the expressions of atherosclerosis(AS)-related inflammatory factors and pro-thrombosis molecules in apolipoprotein E-deficient (ApoE-/-) mice. Methods ApoE-/- mice were randomly divided into normal saline (NS) group, 100 µg anti-ß2GPI Ab group, 100 µg homologous antibody (rabbit-IgG) group and 100 µg ß2GPI/anti-ß2GPI Ab complex group after silastic collars were placed around their carotid arteries by surgery. All mice were fed a high fat diet and corresponding stimuli were given through intraperitoneal injection at 7-day intervals. Six weeks later, the mice were executed. The blockage of carotid arteries of the operated side was observed by HE staining. The expressions of TLR4, tissue factor (TF) and von Willebrand factor (vWF) were detected by immunohistochemistry. The mRNA levels of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in aorta were tested by real-time quantitative PCR. Results HE staining showed that the blockage of carotid arteries in antibody group was the most obvious. The immunohistochemistry showed that the expressions of TLR4, TF and vWF in anti-ß2GPI Ab group increased remarkably. Furthermore, the mRNA levels of IL-1ß and TNF-α in anti-ß2GPI Ab group were higher than those in the other groups. Conclusion The anti-ß2GPI antibody promotes the formation of atherosclerotic plaques in mice by up-regulating the release of inflammatory cytokines IL-1ß, TNF-α and thrombosis-related molecules TF, vWF and TLR4, ultimately enhancing the development of AS.

Curcumin inhibits gastric cancer-derived mesenchymal stem cells mediated angiogenesis by regulating NF-κB/VEGF signaling.

Cancer-derived mesenchymal stem cells (MSCs) seem to play an important role in mediating tumor angiogenesis. Recently, curcumin has been shown to display multiple therapeutic properties, including anticancer activity. In the present study, we have tried to explore the role of curcumin in regulating gastric cancer cells-derived mesenchymal stem cells (GC-MSCs) mediated angiogenesis. Our results showed that curcumin attenuated the high expression levels of fibroblast proteins (α-SMA & Vimentin) in GC-MSCs. Its treatment also inhibited GC-MSCs induced human umbilical vein endothelial cells (HUVEC) tube formation, migration and colony formation. Furthermore, it was noticed that curcumin abrogated NF-κB signaling activity and VEGF production in GC-MSCs. Next, to establish the link between regulation of NF-κB/VEGF signaling by curcumin, and its influence on GC-MSC-derived angiogenesis, we pretreated GC-MSCs with either NF-κB inhibitor PDTC or a neutralizing antibody against VEGF (NA-VEGF), and then collected conditioned media (CM). The HUVEC cells were then cultured in this conditioned media to test their ability to form tubes, migrate and form colonies. Our results demonstrated that NF-κB/VEGF signaling is important for GC-MSCs induced tube formation, migration and colony formation in HUVEC cells. Moreover, we also observed that NF-κB/VEGF signaling regulated VEGF expression of gastric cancer cells both in vitro and in vivo. Overall, our study indicated that curcumin may serve as a novel therapeutic target for GC-MSCs derived angiogenesis, by inhibiting NF-κB/VEGF signaling.

[TLR2 blockade reduces TNF-α expression induced by ß2GP1/anti-ß2GP1 complex in mouse peritoneal macrophages].

OBJECTIVE: To investigate the role of Toll-like receptor 2 (TLR2) in ß2-glycoprotein 1/anti-ß2-glycoprotein 1 (ß2GP1/anti-ß2GP1)-mediated tumor necrosis factor α (TNF-α) expression in mouse peritoneal macrophages. METHODS: The peritoneal macrophages from BALB/c mice were treated with ß2GP1/anti-ß2GP1 complex, agonist of TLR2 (Pam3CSK4) and agonist of TLR4 [lipopolysaccharide (LPS)], inhibitor of TLR2 [monoclonal IgG to mouse TLR2 (anti-mTLR2-IgG)] and inhibitor of TLR4 (TAK-242) in vitro. The mRNA level of TNF-α in the peritoneal macrophages was tested by real-time quantitative PCR, the protein expression of TNF-α was detected by Western blotting and immunofluorescence cytochemistry, and the expression of TLR2 on the surface of the peritoneal macrophages was assessed by flow cytometry. RESULTS: The mRNA and protein expression of TNF-α was significantly enhanced in mouse peritoneal macrophages treated with ß2GP1/anti-ß2GP1 complex, Pam3CSK4 and LPS. Anti-mTLR2-IgG could inhibit the effects of the above stimuli on TNF-α expression, but its effects were weaker than those of TAK-242. Meanwhile, the combination of anti-mTLR2-IgG and TAK-242 did not show much stronger inhibitory effects. Flow cytometry analysis showed that expression of TLR2 was enhanced by ß2GP1/anti-ß2GP1 complex, Pam3CSK4 and LPS in mouse peritoneal macrophages. However, anti-mTLR2-IgG, or TAK-242, or combination of both could not inhibit TLR2 expression in macrophages. CONCLUSION: Both TLR4 and TLR2 could increase the stimulating effect of ß2GP1/anti-ß2GP1 complex on the expression of TNF-α in mouse peritoneal macrophages.