BACKGROUND Advanced glycation end products(AGEs)are diabetic metabolic toxic products that cannot be ignored.Nε-(carboxymethyl)lysine(CML),a component of AGEs,could increase macrophage lipid uptake,promote foam cell ...BACKGROUND Advanced glycation end products(AGEs)are diabetic metabolic toxic products that cannot be ignored.Nε-(carboxymethyl)lysine(CML),a component of AGEs,could increase macrophage lipid uptake,promote foam cell formation,and thereby accelerate atherosclerosis.The receptor for AGEs(RAGE)and cluster of differentiation 36(CD36)were the receptors of CML.However,it is still unknown whether RAGE and CD36 play key roles in CML-promoted lipid uptake.AIM Our study aimed to explore the role of RAGE and CD36 in CML-induced macrophage lipid uptake.METHODS In this study,we examined the effect of CML on lipid uptake by Raw264.7 macrophages.After adding 10 mmol/L CML,the lipid accumulation in macrophages was confirmed by oil red O staining.Expression changes of CD36 and RAGE were detected with immunoblotting and quantitative real-time polymerase chain reaction.The interaction between CML with CD36 and RAGE was verified by immunoprecipitation.We synthesized a novel N-succinimidyl-4-18Ffluorobenzoate-CML radioactive probe.Radioactive receptor-ligand binding assays were performed to test the binding affinity between CML with CD36 and RAGE.The effects of blocking CD36 or RAGE on CML-promoting lipid uptake were also detected.RESULTS The study revealed that CML significantly promoted lipid uptake by macrophages.Immunoprecipitation and radioactive receptor-ligand binding assays indicated that CML could specifically bind to both CD36 and RAGE.CML had a higher affinity for CD36 than RAGE.ARG82,ASN71,and THR70 were the potential interacting amino acids that CD36 binds to CML Anti-CD36 and anti-RAGE could block the uptake of CML by macrophages.The lipid uptake promotion effect of CML was significantly attenuated after blocking CD36 or RAGE.CONCLUSION Our results suggest that the binding of CML with CD36 and RAGE promotes macrophage lipid uptake.展开更多
AIM:To evaluate the serum levels of endozepine-4,their relation with ammonia serum levels,the grading of coma and the severity of cirrhosis,in patients with hepatic coma. METHODS:In this study we included 20 subjects ...AIM:To evaluate the serum levels of endozepine-4,their relation with ammonia serum levels,the grading of coma and the severity of cirrhosis,in patients with hepatic coma. METHODS:In this study we included 20 subjects with Hepatic coma,20 subjects with minimal hepatic encephalopathy(MHE) and 20 subjects control. All subjects underwent blood analysis,Child Pugh and Model for End- stage liver disease(MELD) assessment,endozepine-4 analysis. RESULTS:Subjects with hepatic coma showed significant difference in endozepine-4(P < 0.001) and NH3 levels(P < 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4 we observed a significant correlation(P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD(P = 0.017; Pearsoncorrelation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma,with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia(P < 0.001). In patients with grade Ⅳ hepatic coma,endozepine levels were significantly higher compared to other groups. CONCLUSION:This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion,data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.展开更多
Background: Globally, UNAIDS report 2022 shows, there are 84.2 million people affected by HIV/AIDS and 40.1 million deaths from AIDS since the start of epidemic. In sub-Saharan Africa, women and girls accounted for 63...Background: Globally, UNAIDS report 2022 shows, there are 84.2 million people affected by HIV/AIDS and 40.1 million deaths from AIDS since the start of epidemic. In sub-Saharan Africa, women and girls accounted for 63% of all new HIV infections in 2021 with, six in seven new HIV infections among adolescents aged 15 - 19 years being girls. Key populations accounted for 70% of HIV infections globally in 2021, with 51% of these new HIV infections in sub-Saharan Africa. Reflecting on the 4 decades’ journey of HIV epidemic amidst local, national and international efforts, the UN target of ending AIDS as a public health threat by 2030 remains questionable unless new innovative ways are used. This study aimed at analyzing existing HIV/AIDS interventions, discuss UN interventions in line with ending HIV/AIDS by 2030 then, suggest and discuss new innovative ways of ending HIV scourge by 2030. Methods: Systematic literature review methodology was used to extract existing published information on HIV prevention strategies from 1981 to 2023. The articles were previewed by 2 experts for quality and grouped by intervention. Of the 637 articles accessed, on HIV prevention/control only 45 met the inclusion criteria. Data were synthesized using a narrative synthesis approach following standard guidelines on synthesis without meta-analysis. Descriptive analysis was done, strength and limitations were identified. UNAIDS recommendations for ending HIV/AIDS by 2030 identified and analyzed. New Innovations in HIV/AIDS were presented and discussed. The scope of the reviewed literature was limited to HIV preventive strategies practiced between 1981 and 2023. Results: Findings show that, Uganda’s HIV prevalence was at a peak in 1991 of 15% (30% among pregnant women in urban areas). ABC strategy is claimed to have turned sharply downward the prevalence through the mid-1990s and reached 5% (14% for pregnant urban women) by 2001. Analysis of the strategy showed that the achievements of the strategy could not be sustained, subsequently HIV prevalence rose again. This is because none of the ABC components can independently reduce HIV problem. In the real world, 100% abstinence has failed, condom use only reduces infection by 90% (WHO), and lifelong monogamy is impractical. Such limitations weaken ABC strategy. The study established that Post-exposure prophylaxis (PEP) i.e. taking HIV medicines within 72 hours (3 days) after a possible exposure to HIV infection is a safe, effective and a globally practiced HIV preventive intervention in emergency situations of HIV exposure. However, PEP is limited to care sought within 72 hours after exposure and yet timely access especially in rural areas and for key populations remains a big challenge. Oral PrEP was also identified as effective HIV preventive measure that can reduce HIV risk from sex by about 99% and from injection drug users by 74%. However, like PEP, timely access especially in rural areas and for key populations remains a big challenge. The UNAIDS 95-95-95 strategy (i.e. 95% of people know their HIV status, 95% with +HIV status be on sustained ART and 95% on ART get viral load suppression) formed the basis for setting the target of ending HIV/AIDS epidemic by 2030. However, our analysis shows that this target is unrealistic given the above highlighted limitations/ barriers in preventive measures and the unlikely perfect adherence (100%) to ART by all enrolled HIV positive persons. Conclusion: Ending HIV/AIDS by 2030 cannot be achieved by implementing the current preventing strategies and control measures. This study established that most of the existing HIV preventive strategies and control measures have a number of limitations. However, with sustained UN 95-95-95 strategy supplemented with additional innovative ways, there is hope that the UN dream of ending HIV/AIDS though not necessarily by 2030, can in the long run be achieved.展开更多
Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube developme...Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with com- mercial food containing 3% advanced glycation end product bovine serum albumin （AGE-BSA） or 3% bovine serum albumin （BSA） as a control. After mating mice, oxidative stress markers including malondialdehyde and H202 were measured at embryonic day 7.5 （E7.5） of ges- tation, and the level of intracellular reactive oxygen species （ROS） in embryonic cells was determined at E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-（carboxymethyl） lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at El0.5 in embryos of mice fed with AGE-BSA （no hyperglycemia） compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-（carboxymethyl） lysine and N（ε）-（carboxyethyl） lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.展开更多
The polymerization of methyl methacrylate (MMA) initiated by organic peroxide and polymerizable aromatic tertiary amine such as N, N-di (2-α-methylacryloyloxy propyl)-p-toluidine (MP)_2PT binary system has been studi...The polymerization of methyl methacrylate (MMA) initiated by organic peroxide and polymerizable aromatic tertiary amine such as N, N-di (2-α-methylacryloyloxy propyl)-p-toluidine (MP)_2PT binary system has been studied. It was found that the (MP)_2PT promotes MMA polymerization, and the kinetics of MMA polymerization fits the radical polymerization rate equation. Based on the ESR studies and the end-group analysis the initiation mechanism is proposed.展开更多
基金Supported by The National Natural Science Foundation of China,No.82070455Natural Science Foundation of Jiangsu Province,No.BK20201225Medical Innovation Team Project of Jiangsu Province,No.CXTDA2017010。
文摘BACKGROUND Advanced glycation end products(AGEs)are diabetic metabolic toxic products that cannot be ignored.Nε-(carboxymethyl)lysine(CML),a component of AGEs,could increase macrophage lipid uptake,promote foam cell formation,and thereby accelerate atherosclerosis.The receptor for AGEs(RAGE)and cluster of differentiation 36(CD36)were the receptors of CML.However,it is still unknown whether RAGE and CD36 play key roles in CML-promoted lipid uptake.AIM Our study aimed to explore the role of RAGE and CD36 in CML-induced macrophage lipid uptake.METHODS In this study,we examined the effect of CML on lipid uptake by Raw264.7 macrophages.After adding 10 mmol/L CML,the lipid accumulation in macrophages was confirmed by oil red O staining.Expression changes of CD36 and RAGE were detected with immunoblotting and quantitative real-time polymerase chain reaction.The interaction between CML with CD36 and RAGE was verified by immunoprecipitation.We synthesized a novel N-succinimidyl-4-18Ffluorobenzoate-CML radioactive probe.Radioactive receptor-ligand binding assays were performed to test the binding affinity between CML with CD36 and RAGE.The effects of blocking CD36 or RAGE on CML-promoting lipid uptake were also detected.RESULTS The study revealed that CML significantly promoted lipid uptake by macrophages.Immunoprecipitation and radioactive receptor-ligand binding assays indicated that CML could specifically bind to both CD36 and RAGE.CML had a higher affinity for CD36 than RAGE.ARG82,ASN71,and THR70 were the potential interacting amino acids that CD36 binds to CML Anti-CD36 and anti-RAGE could block the uptake of CML by macrophages.The lipid uptake promotion effect of CML was significantly attenuated after blocking CD36 or RAGE.CONCLUSION Our results suggest that the binding of CML with CD36 and RAGE promotes macrophage lipid uptake.
文摘AIM:To evaluate the serum levels of endozepine-4,their relation with ammonia serum levels,the grading of coma and the severity of cirrhosis,in patients with hepatic coma. METHODS:In this study we included 20 subjects with Hepatic coma,20 subjects with minimal hepatic encephalopathy(MHE) and 20 subjects control. All subjects underwent blood analysis,Child Pugh and Model for End- stage liver disease(MELD) assessment,endozepine-4 analysis. RESULTS:Subjects with hepatic coma showed significant difference in endozepine-4(P < 0.001) and NH3 levels(P < 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4 we observed a significant correlation(P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD(P = 0.017; Pearsoncorrelation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma,with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia(P < 0.001). In patients with grade Ⅳ hepatic coma,endozepine levels were significantly higher compared to other groups. CONCLUSION:This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion,data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.
文摘Background: Globally, UNAIDS report 2022 shows, there are 84.2 million people affected by HIV/AIDS and 40.1 million deaths from AIDS since the start of epidemic. In sub-Saharan Africa, women and girls accounted for 63% of all new HIV infections in 2021 with, six in seven new HIV infections among adolescents aged 15 - 19 years being girls. Key populations accounted for 70% of HIV infections globally in 2021, with 51% of these new HIV infections in sub-Saharan Africa. Reflecting on the 4 decades’ journey of HIV epidemic amidst local, national and international efforts, the UN target of ending AIDS as a public health threat by 2030 remains questionable unless new innovative ways are used. This study aimed at analyzing existing HIV/AIDS interventions, discuss UN interventions in line with ending HIV/AIDS by 2030 then, suggest and discuss new innovative ways of ending HIV scourge by 2030. Methods: Systematic literature review methodology was used to extract existing published information on HIV prevention strategies from 1981 to 2023. The articles were previewed by 2 experts for quality and grouped by intervention. Of the 637 articles accessed, on HIV prevention/control only 45 met the inclusion criteria. Data were synthesized using a narrative synthesis approach following standard guidelines on synthesis without meta-analysis. Descriptive analysis was done, strength and limitations were identified. UNAIDS recommendations for ending HIV/AIDS by 2030 identified and analyzed. New Innovations in HIV/AIDS were presented and discussed. The scope of the reviewed literature was limited to HIV preventive strategies practiced between 1981 and 2023. Results: Findings show that, Uganda’s HIV prevalence was at a peak in 1991 of 15% (30% among pregnant women in urban areas). ABC strategy is claimed to have turned sharply downward the prevalence through the mid-1990s and reached 5% (14% for pregnant urban women) by 2001. Analysis of the strategy showed that the achievements of the strategy could not be sustained, subsequently HIV prevalence rose again. This is because none of the ABC components can independently reduce HIV problem. In the real world, 100% abstinence has failed, condom use only reduces infection by 90% (WHO), and lifelong monogamy is impractical. Such limitations weaken ABC strategy. The study established that Post-exposure prophylaxis (PEP) i.e. taking HIV medicines within 72 hours (3 days) after a possible exposure to HIV infection is a safe, effective and a globally practiced HIV preventive intervention in emergency situations of HIV exposure. However, PEP is limited to care sought within 72 hours after exposure and yet timely access especially in rural areas and for key populations remains a big challenge. Oral PrEP was also identified as effective HIV preventive measure that can reduce HIV risk from sex by about 99% and from injection drug users by 74%. However, like PEP, timely access especially in rural areas and for key populations remains a big challenge. The UNAIDS 95-95-95 strategy (i.e. 95% of people know their HIV status, 95% with +HIV status be on sustained ART and 95% on ART get viral load suppression) formed the basis for setting the target of ending HIV/AIDS epidemic by 2030. However, our analysis shows that this target is unrealistic given the above highlighted limitations/ barriers in preventive measures and the unlikely perfect adherence (100%) to ART by all enrolled HIV positive persons. Conclusion: Ending HIV/AIDS by 2030 cannot be achieved by implementing the current preventing strategies and control measures. This study established that most of the existing HIV preventive strategies and control measures have a number of limitations. However, with sustained UN 95-95-95 strategy supplemented with additional innovative ways, there is hope that the UN dream of ending HIV/AIDS though not necessarily by 2030, can in the long run be achieved.
基金supported by the grant from Shaanxi Technology Committee of China,No.2013JM4001the China Scholarship Council(CSC)
文摘Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with com- mercial food containing 3% advanced glycation end product bovine serum albumin （AGE-BSA） or 3% bovine serum albumin （BSA） as a control. After mating mice, oxidative stress markers including malondialdehyde and H202 were measured at embryonic day 7.5 （E7.5） of ges- tation, and the level of intracellular reactive oxygen species （ROS） in embryonic cells was determined at E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-（carboxymethyl） lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at El0.5 in embryos of mice fed with AGE-BSA （no hyperglycemia） compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-（carboxymethyl） lysine and N（ε）-（carboxyethyl） lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.
文摘The polymerization of methyl methacrylate (MMA) initiated by organic peroxide and polymerizable aromatic tertiary amine such as N, N-di (2-α-methylacryloyloxy propyl)-p-toluidine (MP)_2PT binary system has been studied. It was found that the (MP)_2PT promotes MMA polymerization, and the kinetics of MMA polymerization fits the radical polymerization rate equation. Based on the ESR studies and the end-group analysis the initiation mechanism is proposed.
