BACKGROUND Diabetic nephropathy(DN)is a microangiopathy of type 2 diabetes mellitus(T2DM),which can damage the kidney through various ways and mechanisms due to the nature of the disease,involving the renal interstiti...BACKGROUND Diabetic nephropathy(DN)is a microangiopathy of type 2 diabetes mellitus(T2DM),which can damage the kidney through various ways and mechanisms due to the nature of the disease,involving the renal interstitium and glomeruli.However,in the early stage of the disease,patients only showed kidney volume increase and glomerular hyperthyroidism,and typical symptoms that are difficult to arouse individual attention were noticed.AIM To observe the expression of serum retinol-binding protein(RBP)and urinary Nacetyl-β-D-glucosaminidase(NAG)in patients with DN,and to analyze their value in disease prediction,so as to provide new targets for early diagnosis and treatment of DN.METHODS The baseline data of 50 T2DM patients treated in our hospital between January 2021 and December 2022 were retrospectively reviewed and included in group A.The baseline data of 50 patients with type 2 DN admitted to our hospital during the same period were collected and included in group B.The baseline data and serum RBP and urine NAG expression were compared between the two groups to analyze their value in the early prediction of DN.RESULTS There was no significant difference in age,gender,duration of diabetes,combined hyperlipidemia and combined hypertension between the two groups(P>0.05);the expression of urinary NAG and serum RBP in group B was higher than that in group A,and the difference was statistically significant(P<0.05);a multiple logistic regression model was established,and the results showed that urinary NAG and serum RBP were related to the presence or absence of injury in diabetic patients,and overexpression of urinary NAG and serum RBP may be risk factors for renal injury in T2DM patients(OR>1,P<0.05);receiver operating curve curve was plotted,and the results showed that the area under the curve of urinary NAG and serum RBP expression alone and in combination for predicting DN was>0.80,and the predictive value was satisfactory;bivariate Spearman linear correlation analysis showed that there was a positive correlation between urinary NAG and serum RBP expression in patients with DN(r=0.566,P=0.000).CONCLUSION The increased expression of urinary NAG and serum RBP may be the risk factors leading to the progression of T2DM to DN.The possibility of DN can be considered in patients with urinary NAG and serum RBP overexpression by examining the expression of urinary NAG and serum RBP in patients with T2DM in clinical practice.展开更多
Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers fo...Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.Methods:CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis.CRP-bound serum amyloid A(CRP-SAA) was evaluated by coimmunoprecipitation(IP).Serum samples from two independent cohorts with lung cancer(retrospective cohort,242patients;prospective cohort,222 patients) and healthy controls(159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.Results:CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis.CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media.The level of CRP-SAA was significantly higher in patients than in healthy controls(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001).Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer.The elevation of CRPSAA was associated with lower survival rates for both the retrospective(hazard ration[HR]= 2.181,95%confidence interval[CI]= 1.641-2.897,P < 0.001) and the prospective cohorts(HR = 2.744,95%CI = 1.810-4.161,P < 0.001).Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer.Remarkably,in stages l-ll patients,only CRP-SAA,not total SAA or CRP,showed significant association with overall survival in two cohorts.Moreover,univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.Conclusion:CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP,especially in earlystage patients.展开更多
Objective To identify serum diagnosis or progression biomarkers in patients with lung cancer using protein chip profiling analysis. Method Profiling analysis was performed on 450 sera collected from 213 patients with ...Objective To identify serum diagnosis or progression biomarkers in patients with lung cancer using protein chip profiling analysis. Method Profiling analysis was performed on 450 sera collected from 213 patients with lung cancer, 19 with pneumonia, 16 with pulmonary tuberculosis, 65 with laryngeal carcinoma, 55 with laryngopharyngeal carcinoma patients, and 82 normal individuals. A new strategy was developed to identify the biomarkers on chip by trypsin pre-digestion. Results Profiling analysis demonstrated that an 11.6kDa protein was significantly elevated in lung cancer patients, compared with the control groups (P<0.001). The level and percentage of 11.6kDa protein progressively increased with the clinical stages I-IV and were also higher in patients with squamous cell carcinoma than in other subtypes. This biomarker could be decreased after operation or chemotherapy. On the other hand, 11.6kDa protein was also increased in 50% benign diseases of lung and 13% of other cancer controls. After trypsin pre-digestion, a set of new peptide biomarkers was noticed to appear only in the samples containing a 11.6kDa peak. Further identification showed that 2177Da was a fragment of serum amyloid A (SAA, MW 11.6kDa). Two of the new peaks, 1550Da and 1611Da, were defined from the same protein by database searching. This result was further confirmed by partial purification of 11.6kDa protein and MS analysis. Conclusion SAA is a useful biomarker to monitor the progression of lung cancer and can directly identify some biomarkers on chip.展开更多
Objective The changes in serum adipokines and cytokines related to oxidative stress were examined during 3 months ‘Off to On' and ‘On to Off' periods using negatively charged particle-dominant indoor air con...Objective The changes in serum adipokines and cytokines related to oxidative stress were examined during 3 months ‘Off to On' and ‘On to Off' periods using negatively charged particle-dominant indoor air conditions(NCPDIAC).Methods Seven volunteers participated in the study,which included ‘OFF to 3 months ON' periods(ON trials) for a total of 16 times,and ‘ON to 3 months OFF'(OFF trials) periods for a total of 13 times.Results With the exception of one case,serum amyloid A(SAA) levels decreased significantly during the ON trials.Conclusion Considering that SAA is an acute phase reactive protein such as C reactive protein(CRP),this observed decrease might indicate the prevention of cardiovascular and atherosclerotic changes,since an increase in high-sensitive CRP is associated with the subsequent detection of these events.展开更多
The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acu...The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals.展开更多
Secondary amyloid A amyloidosis,a lethal complication,is induced when acute or chronic infection coexists with over-secretion of the serum amyloid A 1(SAA1)protein and deposition in key internal organs.Previously,usin...Secondary amyloid A amyloidosis,a lethal complication,is induced when acute or chronic infection coexists with over-secretion of the serum amyloid A 1(SAA1)protein and deposition in key internal organs.Previously,using the whole-exome sequencing method,we identified a novel deleterious mutation SAA1.2 in rheumatoid arthritis(RA)patients.However,the role of SAA1 in RA pathogenesis and its complications remains unknown.The purpose of this study was to determine the pathogenetic roles of SAA1 protein isoforms in RA progression.We modified an experimental adenovirus infection protocol to introduce SAA1.2 gene alleles into the knee joints of mice and used SAA1.3 and SAA1.5 as controls.Microcomputed tomography analysis was applied to determine changes in bone morphology and density.Immunohistochemical(IHC)analysis,flow cytometry,enzyme-linked immunosorbent assay(ELISA),and real-time polymerase chain reaction(RT-PCR)were used to investigate disease progression and cytokine alterations in the course of adenoviral SAA-induced knee joint inflammation and bone destruction.We found that the arthritis-inducing effect of SAA1.2 transcription in the knee joints and mutant SAA1 protein secretion in blood resulted in the stimulation of immune responses,leading to CD8^(+)T cell and pro-inflammatory cytokine elevation,such as interleukin(IL)-6,IL-22,matrix metalloproteinase(MMP)-3,MMP-9,with subsequent synovial inflammation and bone destruction.These findings indicate that SAA1 protein isoforms,particularly SAA1.2,play a significant role in the induction and progression of RA and may have potential value in the early diagnosis and severity prediction of RA.展开更多
Objective:To investigate the effect of Chaiqinchengqi decoction(CQCQD) on serum amyloid A (SAA) in severe acute pancreatitis(SAP) patients.Methods:Thirty-five participants enrolled and were randomly assigned into eith...Objective:To investigate the effect of Chaiqinchengqi decoction(CQCQD) on serum amyloid A (SAA) in severe acute pancreatitis(SAP) patients.Methods:Thirty-five participants enrolled and were randomly assigned into either a treatment condition(n=17,treated with CQCQD) or a control condition(n=18,treated with placebo) 24 hours following the onset of the disease. No statistical difference was observed in either group at baseline.Upon admission,the Acute Physiology and Chronic Health Evaluation scoreⅡ(APACHEⅡ),SAA,serum C-reactive protein (CRP) and interleukin-6(IL-6) were measured,as well as on the first,3rd and 7lh day and were compared between the two groups.Organ complications,infection,operation rate,mortality and hospital stay were also compared.Results:The duration of acute respiratory distress syndrome, acute hepatitis,acute renal failure,gastrointestinal failure and blood coagulation dysfunction were shorter in the treatment group than in those in the control group(P【0.05).The secondary infection rates and the hospital fees in the treatment group were lower than those in the control group(P【0.05) as well as length of hospital stay(P【0.01).After 3 days of hospitalization,the APACHEⅡ,score SAA levels,serum CRP and IL-6 in the treatment group was lower than those in the control group(P【0.05).SAA was positively correlated with serum CRP(R = 0.346,P = 0.042),Ranson score(R = 0.442,P = 0.008) and serum IL-6(R=0.359,P =0.034).The area under the receiver operating characteristic curve of admission SAA predict pancreatic necrosis(PN) was 0.815(95%CI:0.625-0.954;P =0.006).The best cut-off value of admission SAA was 7.85 mg/L with the sensitivity 84.6%and specificity 68.2%.Conclusions:The CQCQD can reduce the duration of organ damage through lowering the SAA in SAP patients and the SAA can early predict the PN and severity of SAP patients.展开更多
BACKGROUND Serum amyloid A(SAA)is an acute phase protein mainly synthesized by the liver.SAA induces inflammatory phenotype and promotes cell proliferation in activated hepatic stellate cells,the major scar forming ce...BACKGROUND Serum amyloid A(SAA)is an acute phase protein mainly synthesized by the liver.SAA induces inflammatory phenotype and promotes cell proliferation in activated hepatic stellate cells,the major scar forming cells in the liver.However,few studies have reported on the serum levels of SAA in human liver disease and its clinical significance in various liver diseases.AIM To investigate the serum levels of SAA in patients with different liver diseases and analyze the factors associated with the alteration of SAA levels in chronic hepatitis B(CHB)patients.METHODS Two hundred and seventy-eight patients with different liver diseases and 117 healthy controls were included in this study.The patients included 205 with CHB,22 with active autoimmune liver disease(AILD),21 with nonalcoholic steatohepatitis(NASH),14 with drug-induced liver injury(DILI),and 16 with pyogenic liver abscess.Serum levels of SAA and other clinical parameters were collected for the analysis of the factors associated with SAA level.Mann-Whitney U test was used to compare the serum SAA levels of patients with various liver diseases with those of healthy controls.Bonferroni test was applied for post hoc comparisons to control the probability of type 1 error(alpha=0.05/6=0.008).For statistical tests of other variables,P<0.05 was considered statistically significant.Statistically significant factors determined by single factor analysis were further analyzed by binary multivariate logistic regression analysis.RESULTS All patients with active liver diseases had higher serum SAA levels than healthy controls and the inactive CHB patients,with the highest SAA level found in patients with pyogenic liver abscess(398.4±246.8 mg/L).Patients with active AILD(19.73±24.81 mg/L)or DILI(8.036±5.685 mg/L)showed higher SAA levels than those with active CHB(6.621±6.776 mg/L)and NASH(6.624±4.891 mg/L).Single(P<0.001)and multivariate logistic regression analyses(P=0.039)for the CHB patients suggested that patients with active CHB were associated with an SAA serum level higher than 6.4 mg/L.Serum levels of SAA and CRP(C-reactive protein)were positively correlated in patients with CHB(P<0.001),pyogenic liver abscess(P=0.045),and active AILD(P=0.02).Serum levels of SAA(0.80-871.0 mg/L)had a broader fluctuation range than CRP(0.30-271.3 mg/L).CONCLUSION Serum level of SAA is a sensitive biomarker for inflammatory activity of pyogenic liver abscess.It may also be a weak marker reflecting milder inflammatory status in the liver of patients with CHB and other active liver diseases.展开更多
Alzheimer's disease is pathologically defined by accumulation of extracellular amyloid-β(Aβ). Approximately 25 mutations in β-amyloid precursor protein(APP) are pathogenic and cause autosomal dominant Alzheimer...Alzheimer's disease is pathologically defined by accumulation of extracellular amyloid-β(Aβ). Approximately 25 mutations in β-amyloid precursor protein(APP) are pathogenic and cause autosomal dominant Alzheimer's disease. To date, the mechanism underlying the effect of APP mutation on Aβ generation is unclear. Therefore, investigating the mechanism of APP mutation on Alzheimer's disease may help understanding of disease pathogenesis. Thus, APP mutations(A673T, A673 V, E682 K, E693 G, and E693Q) were transiently co-transfected into human embryonic kidney cells. Western blot assay was used to detect expression levels of APP, beta-secretase 1, and presenilin 1 in cells. Enzyme-linked immunosorbent assay was performed to determine Aβ_(1–40) and Aβ_(1–42) levels. Liquid chromatography-tandem mass chromatography was used to examine VVIAT, FLF, ITL, VIV, IAT, VIT, TVI, and VVIA peptide levels. Immunofluorescence staining was performed to measure APP and early endosome antigen 1 immunoreactivity. Our results show that the protective A673 T mutation decreases Aβ_(42)/Aβ_(40) rate by downregulating IAT and upregulating VVIA levels. Pathogenic A673 V, E682 K, and E693 Q mutations promote Aβ_(42)/Aβ_(40) rate by increasing levels of CTF99, Aβ_(42), Aβ_(40), and IAT, and decreasing VVIA levels. Pathogenic E693 G mutation shows no significant change in Aβ_(42)/Aβ_(40) ratio because of inhibition of γ-secretase activity. APP mutations can change location from the cell surface to early endosomes. Our findings confirm that certain APP mutations accelerate Aβ generation by affecting the long Aβ cleavage pathway and increasing Aβ_(42/40) rate, thereby resulting in Alzheimer's disease.展开更多
Hepatocellular adenoma(HCA) was recently classified into four pathological subtypes. There have been few studies describing the findings of contrast-enhanced ultrasonography(CEUS) of each type. Our case concerns a 78-...Hepatocellular adenoma(HCA) was recently classified into four pathological subtypes. There have been few studies describing the findings of contrast-enhanced ultrasonography(CEUS) of each type. Our case concerns a 78-year-old man who had undergone routine medical check-ups for hepatitis C for 11 years. Abdominal ultrasonography showed a 28 mm, hypo-echoic mass in the segment 4 of the liver. His integrating amount of drinking was 670 kg convert into ethanol. CEUS with Sonazoid demonstrated mild uniform hypo-enhancement with inflow of microbubbles from the periphery of the tumor in the arterial phase, and heterogeneously hypo-enhancement in the post vascular phase. Because the mass increased in size within 3 mo, a well differentiated hepatocellular carcinoma was suspected, and hepatic resection was performed. Microscopic findings showed homogeneous cell proliferation with low grade atypia, infiltration of inflammatory cells, ductular reactions, fatty deposit in part, and sinusoidal dilation. Immunohistochemistry revealed geographic positive for serum amyloid A(SAA), focal positive for glutaminesynthetase, diffuse and strong positive for C-reactive protein, and positive for liver-type fatty acid binding protein. These pathological features corresponded to that of an inflammatory HCA. However, we could not make a clear diagnosis, because HCAs were defined as not to arise in cirrhotic liver. Finally, this tumor was diagnosed as a SAA positive hepatocellular neoplasm.展开更多
Curcumin exerts a neuroprotective effect on Alzheimer’s disease;however,it is not known whether microRNAs are involved in this protective effect.This study was conducted using swAPP695-HEK293 cells as an Alzheimer’s...Curcumin exerts a neuroprotective effect on Alzheimer’s disease;however,it is not known whether microRNAs are involved in this protective effect.This study was conducted using swAPP695-HEK293 cells as an Alzheimer’s disease cell model.swAPP695-HEK293 cells were treated with 0,0.5,1,2,5,and 10μM curcumin for 24 hours.The changes in miR-15b-5p,miR-19a-3p,miR-195-5p,miR-101-3p,miR-216b-5p,miR-16-5p and miR-185-5p expression were assessed by real-time quantitative polymerase chain reaction.The mRNA and protein levels of amyloid precursor protein,amyloid-β40 and amyloid-β42 were evaluated by quantitative real-time polymerase chain reaction,western blot assays and enzyme-linked immunosorbent assays.swAPP695-HEK293 cells were transfected with miR-15b-5p mimic,or treated with 1μM curcumin 24 hours before miR-15b-5p inhibitor transfection.The effects of curcumin on amyloid precursor protein,amyloid-β40 and amyloid-β42 levels were evaluated by western blot assays and enzyme-linked immunosorbent assay.Luciferase assays were used to analyze the interaction between miR-15b-5p and the 3′-untranslated region of amyloid precursor protein.The results show that amyloid precursor protein and amyloid-βexpression were enhanced in swAPP695-HEK293 cells compared with HEK293 parental cells.Curcumin suppressed the expression of amyloid precursor protein and amyloid-βand up-regulated the expression of miR-15b-5p in swAPP695-HEK293 cells.In addition,we found a negative association of miR-15b-5p expression with amyloid precursor protein and amyloid-βlevels in the curcumin-treated cells.Luciferase assays revealed that miR-15b-5p impaired the luciferase activity of the plasmid harboring the 3′-untranslated region of amyloid precursor protein.These findings indicate that curcumin down-regulates the expression of amyloid precursor protein and amyloid-βin swAPP695-HEK293 cells,which was partially mediated by miR-15b-5p via targeting of the 3′-untranslated region of amyloid precursor protein.展开更多
The pathological implication of amyloid precursor protein(APP)in Alzheimer’s disease has been widely documented due to its involvement in the generation of amyloid-β peptide.However,the physiological functions of AP...The pathological implication of amyloid precursor protein(APP)in Alzheimer’s disease has been widely documented due to its involvement in the generation of amyloid-β peptide.However,the physiological functions of APP are still poorly understood.APP is considered a multimodal protein due to its role in a wide variety of processes,both in the embryo and in the adult brain.Specifically,APP seems to play a key role in the proliferation,differentiation and maturation of neural stem cells.In addition,APP can be processed through two canonical processing pathways,generating different functionally active fragments:soluble APP-α,soluble APP-β,amyloid-β peptide and the APP intracellular C-terminal domain.These fragments also appear to modulate various functions in neural stem cells,including the processes of proliferation,neurogenesis,gliogenesis or cell death.However,the molecular mechanisms involved in these effects are still unclear.In this review,we summarize the physiological functions of APP and its main proteolytic derivatives in neural stem cells,as well as the possible signaling pathways that could be implicated in these effects.The knowledge of these functions and signaling pathways involved in the onset or during the development of Alzheimer’s disease is essential to advance the understanding of the pathogenesis of Alzheimer’s disease,and in the search for potential therapeutic targets.展开更多
Nickel,an important transi-tion metal element,is one of the trace elements for hu-man body and has a crucial impact on life and health.Some evidences show the excess exposure to metal ions might be associated with neu...Nickel,an important transi-tion metal element,is one of the trace elements for hu-man body and has a crucial impact on life and health.Some evidences show the excess exposure to metal ions might be associated with neurological diseases.Herein,we applied Raman spectroscopy to study the Ni(II)ion effect on kinetics of amyloid fibrillation of hen egg white lysozyme(HEWL)in thermal and acidic conditions.Using the well-known Raman indicators for protein tertiary and secondary structures,we monitored and analyzed the concentration effect of Ni(II)ions on the unfolding of tertiary structures and the transformation of sec-ondary structures.The experimental evidence validates the accelerator role of the metal ion in the kinetics.Notably,the additional analysis of the amide I band profile,combined with thioflavin-T fluorescence assays,clearly indicates the inhibitory effect of Ni(II)ions on the formation of amyloid fibrils with organizedβ-sheets structures.Instead,a more significant promotion influence is affirmed on the assembly into other aggregates with disordered struc-tures.The present results provide rich information about the specific metal-mediated protein fibrillation.展开更多
The interaction between organic molecules and biomaterial surfaces determines the fate of biomaterials during their service life,which is also the research hotspots in the field of biomaterials.To understand the mecha...The interaction between organic molecules and biomaterial surfaces determines the fate of biomaterials during their service life,which is also the research hotspots in the field of biomaterials.To understand the mechanism of protein interaction with magnesium(Mg)degradation,alloying elements,immersion time,protein concentration and surface conditions have been previously considered for the effect of proteins on Mg degradation.However,fluid flow,as one of the critical factors,drew little attention in this case.In the present study,the effect of bovine serum albumin(BSA)and fetal bovine serum(FBS)on Mg degradation was compared under static and dynamic conditions.The results revealed that both BSA and FBS slightly decreased the degradation rate of Mg in Hanks’balanced salt solution(HBSS)under static immersion due to the protein adsorption and the formation of a Ca/P-rich top layer on Mg surface,whereas under dynamic flow condition the degradation of Mg was significantly accelerated in the presence of BSA or FBS.The reasons seemed to stem from the weakened protein adsorption on Mg surface in this case and the dynamically enhanced interaction between proteins and ions/products in solutions,which largely weaken the combination of the top Ca/P-rich layer with the inner corrosion product layer.These results highlight the importance of testing conditions for Mg characterization in vitro and the synergistic effect between different parameters on Mg degradation.展开更多
Pneumoconiosis is a systemic occupational disease that commonly manifests as diffuse fibrosis of the lungs caused by long-term inhalation of silica dust in the production process. The development of pneumoconiosis is ...Pneumoconiosis is a systemic occupational disease that commonly manifests as diffuse fibrosis of the lungs caused by long-term inhalation of silica dust in the production process. The development of pneumoconiosis is a chronic and progressive process;once it occurs, it is irreversible, and gradually develops into lung injury and respiratory failure, and can cause death regardless of exposure to dust. The incidence of pneumoconiosis is the highest in China and the direct and indirect economic loss as a result of pneumoconiosis is approximately 9 billion yuan per year.展开更多
The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be cr...The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be credited in the acknowledgments.展开更多
文摘BACKGROUND Diabetic nephropathy(DN)is a microangiopathy of type 2 diabetes mellitus(T2DM),which can damage the kidney through various ways and mechanisms due to the nature of the disease,involving the renal interstitium and glomeruli.However,in the early stage of the disease,patients only showed kidney volume increase and glomerular hyperthyroidism,and typical symptoms that are difficult to arouse individual attention were noticed.AIM To observe the expression of serum retinol-binding protein(RBP)and urinary Nacetyl-β-D-glucosaminidase(NAG)in patients with DN,and to analyze their value in disease prediction,so as to provide new targets for early diagnosis and treatment of DN.METHODS The baseline data of 50 T2DM patients treated in our hospital between January 2021 and December 2022 were retrospectively reviewed and included in group A.The baseline data of 50 patients with type 2 DN admitted to our hospital during the same period were collected and included in group B.The baseline data and serum RBP and urine NAG expression were compared between the two groups to analyze their value in the early prediction of DN.RESULTS There was no significant difference in age,gender,duration of diabetes,combined hyperlipidemia and combined hypertension between the two groups(P>0.05);the expression of urinary NAG and serum RBP in group B was higher than that in group A,and the difference was statistically significant(P<0.05);a multiple logistic regression model was established,and the results showed that urinary NAG and serum RBP were related to the presence or absence of injury in diabetic patients,and overexpression of urinary NAG and serum RBP may be risk factors for renal injury in T2DM patients(OR>1,P<0.05);receiver operating curve curve was plotted,and the results showed that the area under the curve of urinary NAG and serum RBP expression alone and in combination for predicting DN was>0.80,and the predictive value was satisfactory;bivariate Spearman linear correlation analysis showed that there was a positive correlation between urinary NAG and serum RBP expression in patients with DN(r=0.566,P=0.000).CONCLUSION The increased expression of urinary NAG and serum RBP may be the risk factors leading to the progression of T2DM to DN.The possibility of DN can be considered in patients with urinary NAG and serum RBP overexpression by examining the expression of urinary NAG and serum RBP in patients with T2DM in clinical practice.
基金supported by grants from the Ministry of Science and Technology of China(2011CB504304 and 2012CB967003)the National Natural Science Foundation of China(81271902 and 81230045)
文摘Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.Methods:CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis.CRP-bound serum amyloid A(CRP-SAA) was evaluated by coimmunoprecipitation(IP).Serum samples from two independent cohorts with lung cancer(retrospective cohort,242patients;prospective cohort,222 patients) and healthy controls(159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.Results:CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis.CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media.The level of CRP-SAA was significantly higher in patients than in healthy controls(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001).Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer.The elevation of CRPSAA was associated with lower survival rates for both the retrospective(hazard ration[HR]= 2.181,95%confidence interval[CI]= 1.641-2.897,P < 0.001) and the prospective cohorts(HR = 2.744,95%CI = 1.810-4.161,P < 0.001).Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer.Remarkably,in stages l-ll patients,only CRP-SAA,not total SAA or CRP,showed significant association with overall survival in two cohorts.Moreover,univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.Conclusion:CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP,especially in earlystage patients.
基金This work was supported by the National Natural Science Foundation of China (Grant No.30370712)Beijing Key Project (Grant No. 7051002)+1 种基金 Beijing Science Technology Committee Project (No.Y0204002040111)a grant of Majon State Basic Research Program of China (No. 2006CB 910100).
文摘Objective To identify serum diagnosis or progression biomarkers in patients with lung cancer using protein chip profiling analysis. Method Profiling analysis was performed on 450 sera collected from 213 patients with lung cancer, 19 with pneumonia, 16 with pulmonary tuberculosis, 65 with laryngeal carcinoma, 55 with laryngopharyngeal carcinoma patients, and 82 normal individuals. A new strategy was developed to identify the biomarkers on chip by trypsin pre-digestion. Results Profiling analysis demonstrated that an 11.6kDa protein was significantly elevated in lung cancer patients, compared with the control groups (P<0.001). The level and percentage of 11.6kDa protein progressively increased with the clinical stages I-IV and were also higher in patients with squamous cell carcinoma than in other subtypes. This biomarker could be decreased after operation or chemotherapy. On the other hand, 11.6kDa protein was also increased in 50% benign diseases of lung and 13% of other cancer controls. After trypsin pre-digestion, a set of new peptide biomarkers was noticed to appear only in the samples containing a 11.6kDa peak. Further identification showed that 2177Da was a fragment of serum amyloid A (SAA, MW 11.6kDa). Two of the new peaks, 1550Da and 1611Da, were defined from the same protein by database searching. This result was further confirmed by partial purification of 11.6kDa protein and MS analysis. Conclusion SAA is a useful biomarker to monitor the progression of lung cancer and can directly identify some biomarkers on chip.
基金supported by a Kawasaki Medical School Research Grant(28B051)
文摘Objective The changes in serum adipokines and cytokines related to oxidative stress were examined during 3 months ‘Off to On' and ‘On to Off' periods using negatively charged particle-dominant indoor air conditions(NCPDIAC).Methods Seven volunteers participated in the study,which included ‘OFF to 3 months ON' periods(ON trials) for a total of 16 times,and ‘ON to 3 months OFF'(OFF trials) periods for a total of 13 times.Results With the exception of one case,serum amyloid A(SAA) levels decreased significantly during the ON trials.Conclusion Considering that SAA is an acute phase reactive protein such as C reactive protein(CRP),this observed decrease might indicate the prevention of cardiovascular and atherosclerotic changes,since an increase in high-sensitive CRP is associated with the subsequent detection of these events.
文摘The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals.
基金funded by The Science and Technology Development Fund,Macao SAR(FDCT-FDCT-17-002-SKL)。
文摘Secondary amyloid A amyloidosis,a lethal complication,is induced when acute or chronic infection coexists with over-secretion of the serum amyloid A 1(SAA1)protein and deposition in key internal organs.Previously,using the whole-exome sequencing method,we identified a novel deleterious mutation SAA1.2 in rheumatoid arthritis(RA)patients.However,the role of SAA1 in RA pathogenesis and its complications remains unknown.The purpose of this study was to determine the pathogenetic roles of SAA1 protein isoforms in RA progression.We modified an experimental adenovirus infection protocol to introduce SAA1.2 gene alleles into the knee joints of mice and used SAA1.3 and SAA1.5 as controls.Microcomputed tomography analysis was applied to determine changes in bone morphology and density.Immunohistochemical(IHC)analysis,flow cytometry,enzyme-linked immunosorbent assay(ELISA),and real-time polymerase chain reaction(RT-PCR)were used to investigate disease progression and cytokine alterations in the course of adenoviral SAA-induced knee joint inflammation and bone destruction.We found that the arthritis-inducing effect of SAA1.2 transcription in the knee joints and mutant SAA1 protein secretion in blood resulted in the stimulation of immune responses,leading to CD8^(+)T cell and pro-inflammatory cytokine elevation,such as interleukin(IL)-6,IL-22,matrix metalloproteinase(MMP)-3,MMP-9,with subsequent synovial inflammation and bone destruction.These findings indicate that SAA1 protein isoforms,particularly SAA1.2,play a significant role in the induction and progression of RA and may have potential value in the early diagnosis and severity prediction of RA.
基金Supported by National Natural Science Foundation of China(No. 81072910)Science and Technology Supports Program of Sichuan(No.2009SZ0201, 2010SZ0068,2011SZ029)
文摘Objective:To investigate the effect of Chaiqinchengqi decoction(CQCQD) on serum amyloid A (SAA) in severe acute pancreatitis(SAP) patients.Methods:Thirty-five participants enrolled and were randomly assigned into either a treatment condition(n=17,treated with CQCQD) or a control condition(n=18,treated with placebo) 24 hours following the onset of the disease. No statistical difference was observed in either group at baseline.Upon admission,the Acute Physiology and Chronic Health Evaluation scoreⅡ(APACHEⅡ),SAA,serum C-reactive protein (CRP) and interleukin-6(IL-6) were measured,as well as on the first,3rd and 7lh day and were compared between the two groups.Organ complications,infection,operation rate,mortality and hospital stay were also compared.Results:The duration of acute respiratory distress syndrome, acute hepatitis,acute renal failure,gastrointestinal failure and blood coagulation dysfunction were shorter in the treatment group than in those in the control group(P【0.05).The secondary infection rates and the hospital fees in the treatment group were lower than those in the control group(P【0.05) as well as length of hospital stay(P【0.01).After 3 days of hospitalization,the APACHEⅡ,score SAA levels,serum CRP and IL-6 in the treatment group was lower than those in the control group(P【0.05).SAA was positively correlated with serum CRP(R = 0.346,P = 0.042),Ranson score(R = 0.442,P = 0.008) and serum IL-6(R=0.359,P =0.034).The area under the receiver operating characteristic curve of admission SAA predict pancreatic necrosis(PN) was 0.815(95%CI:0.625-0.954;P =0.006).The best cut-off value of admission SAA was 7.85 mg/L with the sensitivity 84.6%and specificity 68.2%.Conclusions:The CQCQD can reduce the duration of organ damage through lowering the SAA in SAP patients and the SAA can early predict the PN and severity of SAP patients.
基金the National Natural Science Foundation of China,No.91129705,No.81070340,and No.30570825Science and Technology Commission of Shanghai Municipality,Shanghai Pujiang Talent Program,No.09PJ1402600
文摘BACKGROUND Serum amyloid A(SAA)is an acute phase protein mainly synthesized by the liver.SAA induces inflammatory phenotype and promotes cell proliferation in activated hepatic stellate cells,the major scar forming cells in the liver.However,few studies have reported on the serum levels of SAA in human liver disease and its clinical significance in various liver diseases.AIM To investigate the serum levels of SAA in patients with different liver diseases and analyze the factors associated with the alteration of SAA levels in chronic hepatitis B(CHB)patients.METHODS Two hundred and seventy-eight patients with different liver diseases and 117 healthy controls were included in this study.The patients included 205 with CHB,22 with active autoimmune liver disease(AILD),21 with nonalcoholic steatohepatitis(NASH),14 with drug-induced liver injury(DILI),and 16 with pyogenic liver abscess.Serum levels of SAA and other clinical parameters were collected for the analysis of the factors associated with SAA level.Mann-Whitney U test was used to compare the serum SAA levels of patients with various liver diseases with those of healthy controls.Bonferroni test was applied for post hoc comparisons to control the probability of type 1 error(alpha=0.05/6=0.008).For statistical tests of other variables,P<0.05 was considered statistically significant.Statistically significant factors determined by single factor analysis were further analyzed by binary multivariate logistic regression analysis.RESULTS All patients with active liver diseases had higher serum SAA levels than healthy controls and the inactive CHB patients,with the highest SAA level found in patients with pyogenic liver abscess(398.4±246.8 mg/L).Patients with active AILD(19.73±24.81 mg/L)or DILI(8.036±5.685 mg/L)showed higher SAA levels than those with active CHB(6.621±6.776 mg/L)and NASH(6.624±4.891 mg/L).Single(P<0.001)and multivariate logistic regression analyses(P=0.039)for the CHB patients suggested that patients with active CHB were associated with an SAA serum level higher than 6.4 mg/L.Serum levels of SAA and CRP(C-reactive protein)were positively correlated in patients with CHB(P<0.001),pyogenic liver abscess(P=0.045),and active AILD(P=0.02).Serum levels of SAA(0.80-871.0 mg/L)had a broader fluctuation range than CRP(0.30-271.3 mg/L).CONCLUSION Serum level of SAA is a sensitive biomarker for inflammatory activity of pyogenic liver abscess.It may also be a weak marker reflecting milder inflammatory status in the liver of patients with CHB and other active liver diseases.
基金funded by the National Natural Science Foundation of China,No.81671268(to HQ)partially supported by a grant from the Ministry of Science and Technology of China,No.2013YQ03059514(to HQ)a grant from Key Laboratory for Neurodegenerative Disease of Ministry of Education of China,No.2015SJBX05(to HQ),2015SJZS01(to HQ)
文摘Alzheimer's disease is pathologically defined by accumulation of extracellular amyloid-β(Aβ). Approximately 25 mutations in β-amyloid precursor protein(APP) are pathogenic and cause autosomal dominant Alzheimer's disease. To date, the mechanism underlying the effect of APP mutation on Aβ generation is unclear. Therefore, investigating the mechanism of APP mutation on Alzheimer's disease may help understanding of disease pathogenesis. Thus, APP mutations(A673T, A673 V, E682 K, E693 G, and E693Q) were transiently co-transfected into human embryonic kidney cells. Western blot assay was used to detect expression levels of APP, beta-secretase 1, and presenilin 1 in cells. Enzyme-linked immunosorbent assay was performed to determine Aβ_(1–40) and Aβ_(1–42) levels. Liquid chromatography-tandem mass chromatography was used to examine VVIAT, FLF, ITL, VIV, IAT, VIT, TVI, and VVIA peptide levels. Immunofluorescence staining was performed to measure APP and early endosome antigen 1 immunoreactivity. Our results show that the protective A673 T mutation decreases Aβ_(42)/Aβ_(40) rate by downregulating IAT and upregulating VVIA levels. Pathogenic A673 V, E682 K, and E693 Q mutations promote Aβ_(42)/Aβ_(40) rate by increasing levels of CTF99, Aβ_(42), Aβ_(40), and IAT, and decreasing VVIA levels. Pathogenic E693 G mutation shows no significant change in Aβ_(42)/Aβ_(40) ratio because of inhibition of γ-secretase activity. APP mutations can change location from the cell surface to early endosomes. Our findings confirm that certain APP mutations accelerate Aβ generation by affecting the long Aβ cleavage pathway and increasing Aβ_(42/40) rate, thereby resulting in Alzheimer's disease.
文摘Hepatocellular adenoma(HCA) was recently classified into four pathological subtypes. There have been few studies describing the findings of contrast-enhanced ultrasonography(CEUS) of each type. Our case concerns a 78-year-old man who had undergone routine medical check-ups for hepatitis C for 11 years. Abdominal ultrasonography showed a 28 mm, hypo-echoic mass in the segment 4 of the liver. His integrating amount of drinking was 670 kg convert into ethanol. CEUS with Sonazoid demonstrated mild uniform hypo-enhancement with inflow of microbubbles from the periphery of the tumor in the arterial phase, and heterogeneously hypo-enhancement in the post vascular phase. Because the mass increased in size within 3 mo, a well differentiated hepatocellular carcinoma was suspected, and hepatic resection was performed. Microscopic findings showed homogeneous cell proliferation with low grade atypia, infiltration of inflammatory cells, ductular reactions, fatty deposit in part, and sinusoidal dilation. Immunohistochemistry revealed geographic positive for serum amyloid A(SAA), focal positive for glutaminesynthetase, diffuse and strong positive for C-reactive protein, and positive for liver-type fatty acid binding protein. These pathological features corresponded to that of an inflammatory HCA. However, we could not make a clear diagnosis, because HCAs were defined as not to arise in cirrhotic liver. Finally, this tumor was diagnosed as a SAA positive hepatocellular neoplasm.
基金supported by the Science and Technology Planning Project of Guangdong Province of China,No.2016A020226022(to HYL)the Medical and Health Technology Project of Guangzhou of China,No.20161A011068(to HYL)the Guangzhou Science Technology and Innovation Commission of China,No.201704020043(to QCG)
文摘Curcumin exerts a neuroprotective effect on Alzheimer’s disease;however,it is not known whether microRNAs are involved in this protective effect.This study was conducted using swAPP695-HEK293 cells as an Alzheimer’s disease cell model.swAPP695-HEK293 cells were treated with 0,0.5,1,2,5,and 10μM curcumin for 24 hours.The changes in miR-15b-5p,miR-19a-3p,miR-195-5p,miR-101-3p,miR-216b-5p,miR-16-5p and miR-185-5p expression were assessed by real-time quantitative polymerase chain reaction.The mRNA and protein levels of amyloid precursor protein,amyloid-β40 and amyloid-β42 were evaluated by quantitative real-time polymerase chain reaction,western blot assays and enzyme-linked immunosorbent assays.swAPP695-HEK293 cells were transfected with miR-15b-5p mimic,or treated with 1μM curcumin 24 hours before miR-15b-5p inhibitor transfection.The effects of curcumin on amyloid precursor protein,amyloid-β40 and amyloid-β42 levels were evaluated by western blot assays and enzyme-linked immunosorbent assay.Luciferase assays were used to analyze the interaction between miR-15b-5p and the 3′-untranslated region of amyloid precursor protein.The results show that amyloid precursor protein and amyloid-βexpression were enhanced in swAPP695-HEK293 cells compared with HEK293 parental cells.Curcumin suppressed the expression of amyloid precursor protein and amyloid-βand up-regulated the expression of miR-15b-5p in swAPP695-HEK293 cells.In addition,we found a negative association of miR-15b-5p expression with amyloid precursor protein and amyloid-βlevels in the curcumin-treated cells.Luciferase assays revealed that miR-15b-5p impaired the luciferase activity of the plasmid harboring the 3′-untranslated region of amyloid precursor protein.These findings indicate that curcumin down-regulates the expression of amyloid precursor protein and amyloid-βin swAPP695-HEK293 cells,which was partially mediated by miR-15b-5p via targeting of the 3′-untranslated region of amyloid precursor protein.
基金supported by grants from the Ministerio de Ciencia e Innovación-Instituto de Salud Carlos Ⅲ(PI-10/00291 and MPY1412/09)Ministerio de Economía y Competitividad(SAF2015-71140-R)+2 种基金Comunidad de Madrid(Neurostem-Comunidad de Madrid consortium S2010/BMD-2336)supported by grants from Plan de Empleo Juvenil-Ministerio de Economía y Competitividad
文摘The pathological implication of amyloid precursor protein(APP)in Alzheimer’s disease has been widely documented due to its involvement in the generation of amyloid-β peptide.However,the physiological functions of APP are still poorly understood.APP is considered a multimodal protein due to its role in a wide variety of processes,both in the embryo and in the adult brain.Specifically,APP seems to play a key role in the proliferation,differentiation and maturation of neural stem cells.In addition,APP can be processed through two canonical processing pathways,generating different functionally active fragments:soluble APP-α,soluble APP-β,amyloid-β peptide and the APP intracellular C-terminal domain.These fragments also appear to modulate various functions in neural stem cells,including the processes of proliferation,neurogenesis,gliogenesis or cell death.However,the molecular mechanisms involved in these effects are still unclear.In this review,we summarize the physiological functions of APP and its main proteolytic derivatives in neural stem cells,as well as the possible signaling pathways that could be implicated in these effects.The knowledge of these functions and signaling pathways involved in the onset or during the development of Alzheimer’s disease is essential to advance the understanding of the pathogenesis of Alzheimer’s disease,and in the search for potential therapeutic targets.
基金supported by the National Natural Science Foundation of China(No.22073088,No.22027801 and No.21873089).
文摘Nickel,an important transi-tion metal element,is one of the trace elements for hu-man body and has a crucial impact on life and health.Some evidences show the excess exposure to metal ions might be associated with neurological diseases.Herein,we applied Raman spectroscopy to study the Ni(II)ion effect on kinetics of amyloid fibrillation of hen egg white lysozyme(HEWL)in thermal and acidic conditions.Using the well-known Raman indicators for protein tertiary and secondary structures,we monitored and analyzed the concentration effect of Ni(II)ions on the unfolding of tertiary structures and the transformation of sec-ondary structures.The experimental evidence validates the accelerator role of the metal ion in the kinetics.Notably,the additional analysis of the amide I band profile,combined with thioflavin-T fluorescence assays,clearly indicates the inhibitory effect of Ni(II)ions on the formation of amyloid fibrils with organizedβ-sheets structures.Instead,a more significant promotion influence is affirmed on the assembly into other aggregates with disordered struc-tures.The present results provide rich information about the specific metal-mediated protein fibrillation.
基金the financial supports from China Scholarship Council(CSC,201509350010)Helmholtz Association of German Research Centres.
文摘The interaction between organic molecules and biomaterial surfaces determines the fate of biomaterials during their service life,which is also the research hotspots in the field of biomaterials.To understand the mechanism of protein interaction with magnesium(Mg)degradation,alloying elements,immersion time,protein concentration and surface conditions have been previously considered for the effect of proteins on Mg degradation.However,fluid flow,as one of the critical factors,drew little attention in this case.In the present study,the effect of bovine serum albumin(BSA)and fetal bovine serum(FBS)on Mg degradation was compared under static and dynamic conditions.The results revealed that both BSA and FBS slightly decreased the degradation rate of Mg in Hanks’balanced salt solution(HBSS)under static immersion due to the protein adsorption and the formation of a Ca/P-rich top layer on Mg surface,whereas under dynamic flow condition the degradation of Mg was significantly accelerated in the presence of BSA or FBS.The reasons seemed to stem from the weakened protein adsorption on Mg surface in this case and the dynamically enhanced interaction between proteins and ions/products in solutions,which largely weaken the combination of the top Ca/P-rich layer with the inner corrosion product layer.These results highlight the importance of testing conditions for Mg characterization in vitro and the synergistic effect between different parameters on Mg degradation.
基金supported by Nanjing Medical Technology Development Funds [YKK15188]Nanjing Medical Science and technique Development Foundation [QRX17197]
文摘Pneumoconiosis is a systemic occupational disease that commonly manifests as diffuse fibrosis of the lungs caused by long-term inhalation of silica dust in the production process. The development of pneumoconiosis is a chronic and progressive process;once it occurs, it is irreversible, and gradually develops into lung injury and respiratory failure, and can cause death regardless of exposure to dust. The incidence of pneumoconiosis is the highest in China and the direct and indirect economic loss as a result of pneumoconiosis is approximately 9 billion yuan per year.
文摘The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be credited in the acknowledgments.