Objective To investigate the effects of the total saponin of Dipsacus asperoides (tSDA) and ginsenoside Rb1 (GRb1) on the apoptosis of primary cultured hippocampal neurons induced by β-amyloid protein (Aβ). Methods...Objective To investigate the effects of the total saponin of Dipsacus asperoides (tSDA) and ginsenoside Rb1 (GRb1) on the apoptosis of primary cultured hippocampal neurons induced by β-amyloid protein (Aβ). Methods Primary cultured hippocampal neurons, the cultures were pretreated with tSDA and GRb1 on 10d for 24 hours respectively. Then the cultures were treated with 35 μmol·L -1 Aβ25-35 for 24 hours, observed the changing of survival rate of neurons and the apoptosis of neurons with biochemical analysis combining immunofluorescent cytochemical double-staining technique. Results Hippocampal neurons were treated with 35 μmol·L -1 Aβ for 24 hours, and survival rate of neurons downed to 52.6%. When neurons were pretreated by tSDA and GRb1, survival rate of neurons increased 11% to 15%. The findings of immunofluorescent cytochemical double-staining indicated that apoptotic neurons were obviously more than that of the blank group, reaching 43.9%.When neurons were pretreated by tSDA and GRb1, apoptotic neurons were downed to 16.6%, 10.8% respectively. Conclusion tSDA had the same effects as GRb1, protecting the neurons, antagonizing neurotoxicity of Aβ, increasing survival rate of neurons, and reducing apoptotic neurons induced by Aβ.展开更多
A sensitive and selective assay of proteins is proposed based on measuring the total internal-reflected resonance light scattering(TIR-RLS) signals produced on the water/tetrachloromethane(H_2O/CCl_4) interface. In an...A sensitive and selective assay of proteins is proposed based on measuring the total internal-reflected resonance light scattering(TIR-RLS) signals produced on the water/tetrachloromethane(H_2O/CCl_4) interface. In an aqueous medium with pH value in the range of 3.29—3.78, electrostatic attraction occurs between the negatively charged Evans Blue(EB) and positively charged proteins, forming hydrophobic ion associates and resulting in EB-protein adsorption on H_2O/CCl_4 interface. The presence of cetyltrimethylammonium bromide prompts this adsorption, resulting in strongly enhanced TIR-RLS signals. The intensity of the enhanced TIR-RLS at 360—370 nm was found to be proportional to the concentration of proteins. For bovine serum albumin and human serum albumin, the linear range of detection is 0.07—1.2 μg/mL and the limits of detection are 6.68 and 6.30 ng/mL(3σ), respectively, while for lysozyme, the linear range of detection is 0.06—1.0 μg/mL and the limit of detection is 6.0 ng/mL(3σ). The content of the total albumin in a human urine sample could be directly determined by using the standard addition method with a percent recovery of 97.6%—104.1%, and the RSD ranging from 1.9% to 4.2%.展开更多
Z-scan technique is an effective tool for measuring the optical nonlinearity of the materials. By using this technique the measurement was made for total protein and albumin. The nonlinear refractive index of the tota...Z-scan technique is an effective tool for measuring the optical nonlinearity of the materials. By using this technique the measurement was made for total protein and albumin. The nonlinear refractive index of the total protein and albumin were found to vary linearly with concentration. Hence by calculating the nonlinear refractive index it is possible to measure their concentration in the sample. The values measured thus are found in equivalence with conventional colorimetric method.展开更多
Posidonia oceanicameadows are experiencing a progressive decline, and monitoring their status is crucial for the maintenance of theseecosystems. We performed a comparativeanalysis of bed density, total phenol content ...Posidonia oceanicameadows are experiencing a progressive decline, and monitoring their status is crucial for the maintenance of theseecosystems. We performed a comparativeanalysis of bed density, total phenol content and protein expression pattern to assess the conservation status ofPosidoniaplants from the S. Marinella (Rome, Italy) meadow. The total phenol content was inversely related to maximum beddensity, confirming the relationship betweenhigh phenol content and stressful conditions. In addition, protein expression pattern profilesshowed that the number of differentially expressed proteins was dramatically reduced in the latest years compared to previous analyses. Our results support the usefulness of integrating solid descriptors, such as phenol content, with novel biochemical/molecular approaches in the monitoring of meadows.展开更多
Background and Aim: Despite the fact that acute appendicitis is the most common surgical emergency all around the world, its diagnosis is still based on clinical evaluation and accuracy of the diagnosis depending on e...Background and Aim: Despite the fact that acute appendicitis is the most common surgical emergency all around the world, its diagnosis is still based on clinical evaluation and accuracy of the diagnosis depending on experience. The aim of this study is to evaluate the role of inflammatory markers in diagnosis of acute appendicitis. Material and Method: The study includes 77 cases with histopathologically proven acute appendicitis and 17 control cases. Blood samples were obtained from all cases and C-reactive protein (CRP), Granulocyte Colony Stimulating Factor (G-CSF) and Total Antioxidant Capacity (TAC) were measured. Findings: In cases with acute appendicitis, CRP and G-CSF levels were found to be related to acute appendicitis;however, TAC was not affected by the disease process. Moreover, CRP and G-CSF levels were correlated with the disease severity. Conclusion: Both CRP and G-CSF can be used in diagnosis of acute appendicitis. Furthermore, increased CRP level can be a marker to show advanced cases. However, G-CSF is not an effective marker to show disease severity.展开更多
The term“undruggable”is to describe molecules that are not targetable or at least hard to target pharmacologically.Unfortunately,some targets with potent oncogenic activity fall into this category,and currently litt...The term“undruggable”is to describe molecules that are not targetable or at least hard to target pharmacologically.Unfortunately,some targets with potent oncogenic activity fall into this category,and currently little is known about how to solve this problem,which largely hampered drug research on human cancers.Ras,as one of the most common oncogenes,was previously considered“undruggable”,but in recent years,a few small molecules like Sotorasib(AMG-510)have emerged and proved their targeted anti-cancer effects.Further,myc,as one of the most studied oncogenes,and tp53,being the most common tumor suppressor genes,are both considered“undruggable”.Many attempts have been made to target these“undruggable”targets,but little progress has been made yet.This article summarizes the current progress of direct and indirect targeting approaches for ras,myc,two oncogenes,and tp53,a tumor suppressor gene.These are potential therapeutic targets but are considered“undruggable”.We conclude with some emerging research approaches like proteolysis targeting chimeras(PROTACs),cancer vaccines,and artificial intelligence(AI)-based drug discovery,which might provide new cues for cancer intervention.Therefore,this review sets out to clarify the current status of targeted anti-cancer drug research,and the insights gained from this review may be of assistance to learn from experience and find new ideas in developing new chemicals that directly target such“undruggable”molecules.展开更多
BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal...BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.展开更多
目的建立四川省遂宁地区表观健康成年人群血浆果糖胺(fructosamine,FMN)、果糖胺/总蛋白比值(fructosamine to total protein ratio,FMN/TP)及果糖胺/清蛋白比值(fructosamine to albumin ratio,FMN/ALB)的参考区间。方法选取2017年1～1...目的建立四川省遂宁地区表观健康成年人群血浆果糖胺(fructosamine,FMN)、果糖胺/总蛋白比值(fructosamine to total protein ratio,FMN/TP)及果糖胺/清蛋白比值(fructosamine to albumin ratio,FMN/ALB)的参考区间。方法选取2017年1～12月遂宁市中心医院健康管理中心14 639例20～79岁的表观健康成年人作为研究对象,其中男性4 811例,女性9 828例,通过问卷调查、体格检查、超声及实验室检查排除呼吸系统、血液系统、内分泌系统、炎症和肿瘤等疾病,检测其血浆FMN、总蛋白(total protein,TP)和清蛋白(albumin,ALB)的浓度并计算该人群FMN/TP及FMN/ALB的浓度水平。根据性别和年龄将研究对象分组(男女各6组:20～29岁组,30～39岁组,40～49岁组,50～59岁组,60～69岁组和70～79岁组),对各组检测结果进行统计学分析,浓度水平差异无统计学意义的各组数据进行合并后,呈正态分布则以均值±1.96标准差■建立该地区表观健康人群血浆中FMN,FMN/TP及FMN/ALB的参考区间;呈偏态分布以百分位数法(P_(2.5)～P_(97.5))建立其参考区间。结果男性血浆FMN,FMN/TP及FMN/ALB浓度水平依次为1.7(1.6～1.8)mmol/L,22.0(20.7～23.5)μmol/g和37.1(34.5～39.8)μmol/g;女性则依次为1.7(1.6～1.8)mmol/L,22.4(21.1～23.9)μmol/g和38.5(36.2～41.2)μmol/g。男性和女性血浆FMN,FMN/TP及FMN/ALB浓度水平均呈偏态分布(P<0.05),且两组间比较差异均具有统计学意义(P<0.01)。进一步分析,男性和女性各年龄组血浆FMN,FMN/TP及FMN/ALB浓度水平的中位数与其总体区间中位数的差异均<25%,故不建议按年龄段分组建立参考区间,可仅按性别分组建立其参考区间。FMN的参考区间:男性为1.4～2.0 mmol/L,女性为1.5～2.0 mmol/L;FMN/TP的参考区间:男性为18.2～26.4μmol/g,女性为18.9～26.8μmol/g;FMN/ALB的参考区间:男性为30.4～46.1μmol/g,女性为32.1～46.9μmol/g。结论初步建立了遂宁地区20～79岁表观健康人群血浆FMN,FMN/TP及FMN/ALB的参考区间,为临床应用其作为糖尿病患者的诊断及疗效评估指标提供依据。展开更多
文摘Objective To investigate the effects of the total saponin of Dipsacus asperoides (tSDA) and ginsenoside Rb1 (GRb1) on the apoptosis of primary cultured hippocampal neurons induced by β-amyloid protein (Aβ). Methods Primary cultured hippocampal neurons, the cultures were pretreated with tSDA and GRb1 on 10d for 24 hours respectively. Then the cultures were treated with 35 μmol·L -1 Aβ25-35 for 24 hours, observed the changing of survival rate of neurons and the apoptosis of neurons with biochemical analysis combining immunofluorescent cytochemical double-staining technique. Results Hippocampal neurons were treated with 35 μmol·L -1 Aβ for 24 hours, and survival rate of neurons downed to 52.6%. When neurons were pretreated by tSDA and GRb1, survival rate of neurons increased 11% to 15%. The findings of immunofluorescent cytochemical double-staining indicated that apoptotic neurons were obviously more than that of the blank group, reaching 43.9%.When neurons were pretreated by tSDA and GRb1, apoptotic neurons were downed to 16.6%, 10.8% respectively. Conclusion tSDA had the same effects as GRb1, protecting the neurons, antagonizing neurotoxicity of Aβ, increasing survival rate of neurons, and reducing apoptotic neurons induced by Aβ.
文摘A sensitive and selective assay of proteins is proposed based on measuring the total internal-reflected resonance light scattering(TIR-RLS) signals produced on the water/tetrachloromethane(H_2O/CCl_4) interface. In an aqueous medium with pH value in the range of 3.29—3.78, electrostatic attraction occurs between the negatively charged Evans Blue(EB) and positively charged proteins, forming hydrophobic ion associates and resulting in EB-protein adsorption on H_2O/CCl_4 interface. The presence of cetyltrimethylammonium bromide prompts this adsorption, resulting in strongly enhanced TIR-RLS signals. The intensity of the enhanced TIR-RLS at 360—370 nm was found to be proportional to the concentration of proteins. For bovine serum albumin and human serum albumin, the linear range of detection is 0.07—1.2 μg/mL and the limits of detection are 6.68 and 6.30 ng/mL(3σ), respectively, while for lysozyme, the linear range of detection is 0.06—1.0 μg/mL and the limit of detection is 6.0 ng/mL(3σ). The content of the total albumin in a human urine sample could be directly determined by using the standard addition method with a percent recovery of 97.6%—104.1%, and the RSD ranging from 1.9% to 4.2%.
文摘Z-scan technique is an effective tool for measuring the optical nonlinearity of the materials. By using this technique the measurement was made for total protein and albumin. The nonlinear refractive index of the total protein and albumin were found to vary linearly with concentration. Hence by calculating the nonlinear refractive index it is possible to measure their concentration in the sample. The values measured thus are found in equivalence with conventional colorimetric method.
文摘Posidonia oceanicameadows are experiencing a progressive decline, and monitoring their status is crucial for the maintenance of theseecosystems. We performed a comparativeanalysis of bed density, total phenol content and protein expression pattern to assess the conservation status ofPosidoniaplants from the S. Marinella (Rome, Italy) meadow. The total phenol content was inversely related to maximum beddensity, confirming the relationship betweenhigh phenol content and stressful conditions. In addition, protein expression pattern profilesshowed that the number of differentially expressed proteins was dramatically reduced in the latest years compared to previous analyses. Our results support the usefulness of integrating solid descriptors, such as phenol content, with novel biochemical/molecular approaches in the monitoring of meadows.
文摘Background and Aim: Despite the fact that acute appendicitis is the most common surgical emergency all around the world, its diagnosis is still based on clinical evaluation and accuracy of the diagnosis depending on experience. The aim of this study is to evaluate the role of inflammatory markers in diagnosis of acute appendicitis. Material and Method: The study includes 77 cases with histopathologically proven acute appendicitis and 17 control cases. Blood samples were obtained from all cases and C-reactive protein (CRP), Granulocyte Colony Stimulating Factor (G-CSF) and Total Antioxidant Capacity (TAC) were measured. Findings: In cases with acute appendicitis, CRP and G-CSF levels were found to be related to acute appendicitis;however, TAC was not affected by the disease process. Moreover, CRP and G-CSF levels were correlated with the disease severity. Conclusion: Both CRP and G-CSF can be used in diagnosis of acute appendicitis. Furthermore, increased CRP level can be a marker to show advanced cases. However, G-CSF is not an effective marker to show disease severity.
基金supported by Grants from the National Natural Science Foundation of China(81902784)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004)+2 种基金the Fund of Sichuan Provincial Department of Science and Technology(2022YFSY0058)the Research Funding(RCDWJS 2020-20)the Research and Development Program(RD-02-202002)from West China School/Hospital of Stomatology Sichuan University.
文摘The term“undruggable”is to describe molecules that are not targetable or at least hard to target pharmacologically.Unfortunately,some targets with potent oncogenic activity fall into this category,and currently little is known about how to solve this problem,which largely hampered drug research on human cancers.Ras,as one of the most common oncogenes,was previously considered“undruggable”,but in recent years,a few small molecules like Sotorasib(AMG-510)have emerged and proved their targeted anti-cancer effects.Further,myc,as one of the most studied oncogenes,and tp53,being the most common tumor suppressor genes,are both considered“undruggable”.Many attempts have been made to target these“undruggable”targets,but little progress has been made yet.This article summarizes the current progress of direct and indirect targeting approaches for ras,myc,two oncogenes,and tp53,a tumor suppressor gene.These are potential therapeutic targets but are considered“undruggable”.We conclude with some emerging research approaches like proteolysis targeting chimeras(PROTACs),cancer vaccines,and artificial intelligence(AI)-based drug discovery,which might provide new cues for cancer intervention.Therefore,this review sets out to clarify the current status of targeted anti-cancer drug research,and the insights gained from this review may be of assistance to learn from experience and find new ideas in developing new chemicals that directly target such“undruggable”molecules.
基金Supported by the National Key Clinical Discipline,Fuzhou “14th Five-Year Plan” Clinical Key Specialty (laboratory medicine)the National Science Foundation of China,No. 82002587
文摘BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.
文摘目的建立四川省遂宁地区表观健康成年人群血浆果糖胺(fructosamine,FMN)、果糖胺/总蛋白比值(fructosamine to total protein ratio,FMN/TP)及果糖胺/清蛋白比值(fructosamine to albumin ratio,FMN/ALB)的参考区间。方法选取2017年1～12月遂宁市中心医院健康管理中心14 639例20～79岁的表观健康成年人作为研究对象,其中男性4 811例,女性9 828例,通过问卷调查、体格检查、超声及实验室检查排除呼吸系统、血液系统、内分泌系统、炎症和肿瘤等疾病,检测其血浆FMN、总蛋白(total protein,TP)和清蛋白(albumin,ALB)的浓度并计算该人群FMN/TP及FMN/ALB的浓度水平。根据性别和年龄将研究对象分组(男女各6组:20～29岁组,30～39岁组,40～49岁组,50～59岁组,60～69岁组和70～79岁组),对各组检测结果进行统计学分析,浓度水平差异无统计学意义的各组数据进行合并后,呈正态分布则以均值±1.96标准差■建立该地区表观健康人群血浆中FMN,FMN/TP及FMN/ALB的参考区间;呈偏态分布以百分位数法(P_(2.5)～P_(97.5))建立其参考区间。结果男性血浆FMN,FMN/TP及FMN/ALB浓度水平依次为1.7(1.6～1.8)mmol/L,22.0(20.7～23.5)μmol/g和37.1(34.5～39.8)μmol/g;女性则依次为1.7(1.6～1.8)mmol/L,22.4(21.1～23.9)μmol/g和38.5(36.2～41.2)μmol/g。男性和女性血浆FMN,FMN/TP及FMN/ALB浓度水平均呈偏态分布(P<0.05),且两组间比较差异均具有统计学意义(P<0.01)。进一步分析,男性和女性各年龄组血浆FMN,FMN/TP及FMN/ALB浓度水平的中位数与其总体区间中位数的差异均<25%,故不建议按年龄段分组建立参考区间,可仅按性别分组建立其参考区间。FMN的参考区间:男性为1.4～2.0 mmol/L,女性为1.5～2.0 mmol/L;FMN/TP的参考区间:男性为18.2～26.4μmol/g,女性为18.9～26.8μmol/g;FMN/ALB的参考区间:男性为30.4～46.1μmol/g,女性为32.1～46.9μmol/g。结论初步建立了遂宁地区20～79岁表观健康人群血浆FMN,FMN/TP及FMN/ALB的参考区间,为临床应用其作为糖尿病患者的诊断及疗效评估指标提供依据。
