Background:Acute pancreatitis(AP),known for its rapid onset and significant incidence and mortality rates,presents a clinical challenge due to the limited availability of effective treatments and preventive measures.A...Background:Acute pancreatitis(AP),known for its rapid onset and significant incidence and mortality rates,presents a clinical challenge due to the limited availability of effective treatments and preventive measures.Anemarsaponin B(ASB)has emerged as a potential therapeutic agent,demonstrating capabilities in reducing immune inflammation,positioning it as a promising candidate for AP treatment.Methods:We investigated the effects of ASB on AP in mice,induced by caerulein and lipopolysaccharide(LPS).Peripheral blood samples were collected 24 h post-induction with caerulein to assess of key biomarkers including lipase,amylase,TNF-α,IL-1β,IL-6,SOD,and GSH-Px.A range of techniques such as immunohistochemistry staining,immunofluorescence staining,Western blotting,and quantitative Polymerase Chain Reaction(q-PCR),were employed to measure the expression of critical genes.Additionally,pancreas samples from the mice were harvested for microbiome and metabolome sequencing,with the data analyzed to understand the impact of ASB on AP.Results:Our study revealed that,compared to the sham group,the AP group exhibited significantly higher serum levels of lipase,amylase,and cytokines,while levels of SOD and GSH Px were notably lower.Treatment with ASB led to a substantial decrease in the levels of lipase,amylase,and cytokines,and an increase in SOD and GSH-Px levels.q-PCR analysis of pancreatic histiocytes corroborated these serum findings.Hematoxylin and Eosin(H&E)staining indicated significant alterations in the pathological changes in the pancreas,lungs,and small intestine of the AP model due to ASB.Immunofluorescence assays demonstrated that ASB alleviated the apoptosis of pancreatic histiocytes in the AP model.Western Blot and histological analyses showed that ASB reduced the phosphorylation of TAK,p38,JNK,and ERK proteins,as well as the levels of TRAF6 protein in the AP model.Furthermore,metabolomic and gut microbiota analysis identified 27 differential metabolites and 34 differential species.The combined metabolome and microbiome analysis suggested an association between certain microbes(e.g.,unclassified-Saprospiraceae and unclassified-Micavibrionales)and metabolites(e.g.,LysoPE(0:0/20:0),PC(DiMe(13,5)/PGJ2)),and Heptanoic acid,indicating potential pathways through which ASB may exert its therapeutic effects in AP.Conclusions:ASB exhibits therapeutic efficacy in treating AP induced by caerulein combined with lipopolysaccharide(LPS),primarily through modulating the mitogenactivated protein kinase(MAPK)signaling pathway.This discovery offers fresh perspectives for AP drug development,underscoring the potential of targeting specific cellular pathways.Additionally,the intricate interplay observed between the gut microbiota and metabolites following ASB treatment highlights novel therapeutic targets,suggesting that manipulating the gut microbiome and metabolome could be a viable strategy in AP management.These findings pave the way for further research into comprehensive treatment approaches that incorporate both pharmacological intervention and microbiota modulation.展开更多
A novel flow-injection chemiluminescence(FI-CL) method free of CL reagent was developed for the determination of captopril based on its enhancing effect on the CL derived from diperiodatoargentate(Ⅲ)-sulfuric acid sy...A novel flow-injection chemiluminescence(FI-CL) method free of CL reagent was developed for the determination of captopril based on its enhancing effect on the CL derived from diperiodatoargentate(Ⅲ)-sulfuric acid system. Compared with the conventional CL system, the CL system based on trivalent silver was characterized of good selectivity for the absence of CL reagent. The CL mechanism was discussed through CL spectra and UV–vis absorption spectra. The conditions of the FI-CL system were investigated and optimized.Under the optimal conditions, the relative CL intensity was linear with the captopril concentration in the range of 0.3–15.0 μg/m L. The detection limit for captopril was 0.05 μg/m L, and the relative standard deviation(n=11) was 2.0% for 5.0 μg/m L captopril. The proposed method was applied to the analysis of captopril in tablet and human urine with the recoveries of 83.1%–112.5%, and the relative standard deviations of 0.5%–4.4%. The results obtained by the proposed method agreed well with those obtained from HPLC method. The proposed method is fast, convenient, and cost-effective for the determination of captopril in medicine and biological samples.展开更多
With the advantages of high sensitivity,rapid response,label-free,and simple operation,field effect transistor biosensors have shown promising application prospects in large-scale pathogen screening.However,in practic...With the advantages of high sensitivity,rapid response,label-free,and simple operation,field effect transistor biosensors have shown promising application prospects in large-scale pathogen screening.However,in practical biological fluids with relatively high ionic strength,such as saliva and serum,the Debye screening effect will weaken the interaction between FET biosensors and target bio-molecules,thereby affecting the sensing sensitivity and accuracy.展开更多
基金sponsored by Natural Science Foundation of Chongqing,China(cstc2021jcyjmsxmX0724,cstc2020jcyj-msxmX0434),Chongqing Key Specialty Fund of Clinical Pharmacy.
文摘Background:Acute pancreatitis(AP),known for its rapid onset and significant incidence and mortality rates,presents a clinical challenge due to the limited availability of effective treatments and preventive measures.Anemarsaponin B(ASB)has emerged as a potential therapeutic agent,demonstrating capabilities in reducing immune inflammation,positioning it as a promising candidate for AP treatment.Methods:We investigated the effects of ASB on AP in mice,induced by caerulein and lipopolysaccharide(LPS).Peripheral blood samples were collected 24 h post-induction with caerulein to assess of key biomarkers including lipase,amylase,TNF-α,IL-1β,IL-6,SOD,and GSH-Px.A range of techniques such as immunohistochemistry staining,immunofluorescence staining,Western blotting,and quantitative Polymerase Chain Reaction(q-PCR),were employed to measure the expression of critical genes.Additionally,pancreas samples from the mice were harvested for microbiome and metabolome sequencing,with the data analyzed to understand the impact of ASB on AP.Results:Our study revealed that,compared to the sham group,the AP group exhibited significantly higher serum levels of lipase,amylase,and cytokines,while levels of SOD and GSH Px were notably lower.Treatment with ASB led to a substantial decrease in the levels of lipase,amylase,and cytokines,and an increase in SOD and GSH-Px levels.q-PCR analysis of pancreatic histiocytes corroborated these serum findings.Hematoxylin and Eosin(H&E)staining indicated significant alterations in the pathological changes in the pancreas,lungs,and small intestine of the AP model due to ASB.Immunofluorescence assays demonstrated that ASB alleviated the apoptosis of pancreatic histiocytes in the AP model.Western Blot and histological analyses showed that ASB reduced the phosphorylation of TAK,p38,JNK,and ERK proteins,as well as the levels of TRAF6 protein in the AP model.Furthermore,metabolomic and gut microbiota analysis identified 27 differential metabolites and 34 differential species.The combined metabolome and microbiome analysis suggested an association between certain microbes(e.g.,unclassified-Saprospiraceae and unclassified-Micavibrionales)and metabolites(e.g.,LysoPE(0:0/20:0),PC(DiMe(13,5)/PGJ2)),and Heptanoic acid,indicating potential pathways through which ASB may exert its therapeutic effects in AP.Conclusions:ASB exhibits therapeutic efficacy in treating AP induced by caerulein combined with lipopolysaccharide(LPS),primarily through modulating the mitogenactivated protein kinase(MAPK)signaling pathway.This discovery offers fresh perspectives for AP drug development,underscoring the potential of targeting specific cellular pathways.Additionally,the intricate interplay observed between the gut microbiota and metabolites following ASB treatment highlights novel therapeutic targets,suggesting that manipulating the gut microbiome and metabolome could be a viable strategy in AP management.These findings pave the way for further research into comprehensive treatment approaches that incorporate both pharmacological intervention and microbiota modulation.
基金supported by the National Natural Science Foundation of China (Nos. 21475153, 21575167, 21675178 and 21605163)the Guangdong Provincial Natural Science Foundation (Nos. 2015A030311020 and 2016A030313358)+1 种基金the Special Funds for Public Welfare Research and Capacity Building in Guangdong Province (No.2015A030401036)the Guangzhou Science and Technology Program (No. 201604020165)
文摘A novel flow-injection chemiluminescence(FI-CL) method free of CL reagent was developed for the determination of captopril based on its enhancing effect on the CL derived from diperiodatoargentate(Ⅲ)-sulfuric acid system. Compared with the conventional CL system, the CL system based on trivalent silver was characterized of good selectivity for the absence of CL reagent. The CL mechanism was discussed through CL spectra and UV–vis absorption spectra. The conditions of the FI-CL system were investigated and optimized.Under the optimal conditions, the relative CL intensity was linear with the captopril concentration in the range of 0.3–15.0 μg/m L. The detection limit for captopril was 0.05 μg/m L, and the relative standard deviation(n=11) was 2.0% for 5.0 μg/m L captopril. The proposed method was applied to the analysis of captopril in tablet and human urine with the recoveries of 83.1%–112.5%, and the relative standard deviations of 0.5%–4.4%. The results obtained by the proposed method agreed well with those obtained from HPLC method. The proposed method is fast, convenient, and cost-effective for the determination of captopril in medicine and biological samples.
基金The National Key R&D Program of China(2017YFA0208000,2021YFA1202400)the New Cornerstone Science Foundation through the XPLORER PRIZE are acknowledged for research fundingthe Core Facility of Wuhan University for ATR-FTIR,SEM,and XPS analysis.The study was approved by the Ethics Committee of Renmin Hospital of Wuhan University(WDRY2022-K257)。
文摘With the advantages of high sensitivity,rapid response,label-free,and simple operation,field effect transistor biosensors have shown promising application prospects in large-scale pathogen screening.However,in practical biological fluids with relatively high ionic strength,such as saliva and serum,the Debye screening effect will weaken the interaction between FET biosensors and target bio-molecules,thereby affecting the sensing sensitivity and accuracy.