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Tityus serrulatus scorpion is responsible for a significant number of envenomings in Brazil, ranging from mild to severe, and in some cases, leading to fatalities. While supportive care is the primary treatment modality, moderate and severe cases require antivenom administration despite potential limitations and adverse effects. The remarkable proliferation of T. serrulatus scorpions, attributed to their biology and asexual reproduction, contributes to a high incidence of envenomation. T. serrulatus scorpion venom predominantly consists of short proteins acting as neurotoxins (α and ß), that primarily target ion channels. Nevertheless, high molecular weight compounds, including metalloproteases, serine proteases, phospholipases, and hyaluronidases, are also present in the venom. These compounds play a crucial role in envenomation, influencing the severity of symptoms and the spread of venom. This review endeavors to comprehensively understand the T. serrulatus scorpion venom by elucidating the primary high molecular weight compounds and exploring their potential contributions to envenomation. Understanding these compounds' mechanisms of action can aid in developing more effective treatments and prevention strategies, ultimately mitigating the impact of scorpion envenomation on public health in Brazil.
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Animals , Scorpion Venoms/analysis , Scorpion Venoms/chemistry , Peptide Hydrolases , Phospholipases , Glycoproteins , HyaluronoglucosaminidaseABSTRACT
OBJECTIVE@#To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice.@*METHODS@#Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR.@*RESULTS@#Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P < 0.001), which were significantly lowered by treatment with TS-MES (P < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P < 0.05).@*CONCLUSION@#Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.
Subject(s)
Animals , Male , Mice , Cytokines , Dexamethasone , Heart Injuries , Interleukin-10 , Interleukin-6 , Larva , Mice, Inbred BALB C , Myocardium , Sepsis , Transforming Growth Factor beta , Trichinella spiralis , Tumor Necrosis Factor-alphaABSTRACT
Objective To investigate the protective effect of excretory-secretory protein (AES) from adult Trichinella spiralis on ovalbumin (OVA)-induced allergic rhinitis in mice. Methods Eighteen female BALB/c mice were randomly divided into three groups, including the blank control group (Group A), OVA-induced rhinitis group (Group B) and AES treatment group (Group C). Mice in Group A were given PBS. Mice in Group B were intraperitoneally injected with antigen adjuvant suspension for systemic sensitization, once every other day for seven times; then, local excitation was intranasally induced with 5% OVA solution once a day for seven times to establish a mouse model of allergic rhinitis. In addition to induction of allergic rhinitis, mice in Group C were given 25 μg AES at baseline sensitization and local excitation. Following the final challenge, mice were observed for 30 min in each group, and the behavioral score was evaluated. The serum levels of IFN-γ, IL-4, IL-5, IL-10 and TGF-β were determined using an enzyme-linked immunosorbent assay in mice, and the pathological changes of mouse nasal mucosa were observed under a microscope. Results There was a significant difference in the mouse behavioral scores among the three groups (F = 110.12, P < 0.01). The mouse behavioral score was significantly higher in Group B than in Group A (7.17 ± 0.75 vs. 1.33 ± 0.52, P < 0.01), and more remarkable pathological damages of mouse nasal mucosa were seen in Group B than in Group A, while the mouse behavioral score was significantly decreased in Group C than in Group B (P < 0.01), and the pathological damages of mouse nasal mucosa remarkably alleviated in Group C relative to Group B. There was a significant difference in serum IFN-γ level among the three groups (F = 7.50, P < 0.01) and the serum IFN-γ level in Group B was significantly lower than in group A and C (both P < 0.05). There were significant differences in serum IL-4 (F = 470.81, P < 0.01) and IL-5 levels (F =68.20, P < 0.01) among the three groups, and significantly greater serum IL-4 and IL-5 levels were detected in Group B than in Group A (P < 0.01), while significantly lower serum IL-4 and IL-5 levels were detected in Group C than in Group B (P < 0.01). There were significant differences in serum IL-10 (F = 174.91, P < 0.01) and TGF-β levels (F = 9.39, P < 0.01) among the three groups, and significantly greater serum IL-10 and TGF-β levels were seen in Group C than in Group B (both P < 0.05). Conclusion T. spiralis AES has a remarkable protective activity against OVA-induced allergic rhinitis in mice.
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Objective To investigate the protective effect of excretory-secretory protein (AES) from adult Trichinella spiralis on ovalbumin (OVA)-induced allergic rhinitis in mice. Methods Eighteen female BALB/c mice were randomly divided into three groups, including the blank control group (Group A), OVA-induced rhinitis group (Group B) and AES treatment group (Group C). Mice in Group A were given PBS. Mice in Group B were intraperitoneally injected with antigen adjuvant suspension for systemic sensitization, once every other day for seven times; then, local excitation was intranasally induced with 5% OVA solution once a day for seven times to establish a mouse model of allergic rhinitis. In addition to induction of allergic rhinitis, mice in Group C were given 25 μg AES at baseline sensitization and local excitation. Following the final challenge, mice were observed for 30 min in each group, and the behavioral score was evaluated. The serum levels of IFN-γ, IL-4, IL-5, IL-10 and TGF-β were determined using an enzyme-linked immunosorbent assay in mice, and the pathological changes of mouse nasal mucosa were observed under a microscope. Results There was a significant difference in the mouse behavioral scores among the three groups (F = 110.12, P < 0.01). The mouse behavioral score was significantly higher in Group B than in Group A (7.17 ± 0.75 vs. 1.33 ± 0.52, P < 0.01), and more remarkable pathological damages of mouse nasal mucosa were seen in Group B than in Group A, while the mouse behavioral score was significantly decreased in Group C than in Group B (P < 0.01), and the pathological damages of mouse nasal mucosa remarkably alleviated in Group C relative to Group B. There was a significant difference in serum IFN-γ level among the three groups (F = 7.50, P < 0.01) and the serum IFN-γ level in Group B was significantly lower than in group A and C (both P < 0.05). There were significant differences in serum IL-4 (F = 470.81, P < 0.01) and IL-5 levels (F =68.20, P < 0.01) among the three groups, and significantly greater serum IL-4 and IL-5 levels were detected in Group B than in Group A (P < 0.01), while significantly lower serum IL-4 and IL-5 levels were detected in Group C than in Group B (P < 0.01). There were significant differences in serum IL-10 (F = 174.91, P < 0.01) and TGF-β levels (F = 9.39, P < 0.01) among the three groups, and significantly greater serum IL-10 and TGF-β levels were seen in Group C than in Group B (both P < 0.05). Conclusion T. spiralis AES has a remarkable protective activity against OVA-induced allergic rhinitis in mice.
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Objective To discuss the serum value of human epididymis protein 4(HE4) in the diagnosis of lung can-cer and to analyse the serum levels of HE4 in different pathological types and TNM staging of lung cancer patients. Meth-ods Forty-seven patients with lung cancer and thirty-one healthy controls were selected to join this study. According to various pathological types and TNM staging, the selected lung cancer patients were divided into different subgroups under the two categories. The serum HE4 levels were compared between subgroups. ROC curves of serum HE4 level and serum CEA level were drawn for the diagnosis of lung cancer with the pathological diagnosis as the golden standard. Results There was significantly higher level of serum HE4 in lung cancer group[(253.47±170.03) pmol/L] than that of healthy group [(84.09±51.03) pmol/L](t=5.365). There were no significant differences in serum levels of HE4 between different pathological subgroups of lung cancer patients [non-small cell carcinoma group (241.34±161.81) pmol/L vs small cell carcinoma group (293.5±198.76) pmol/L, t=0.847;squamous cell carcinoma group (304.29±287.61) pmol/L, adenocarcinoma group (224.39± 122.15) pmol/L and small cell carcinoma group F=0.969;and different TNM staging subgroups [ (stageⅠ~Ⅲgroup (255.27± 183.04) pmol/L vs stageⅣgroup (288.16±216.49) pmol/L, t=0.528]. Compared with ROC curves of serum HE4 and serum CEA,the area under the curve (AUC) of serum HE4 (0.902) was larger than that of serum CEA(0.765),( P>0.001). When the serum level of HE4 was 149.145 pmol/L, the sensitivity and specificity in the diagnosis of lung cancer were 72.3% and 90.3%. When the serum level of CEA was 4.685μg/L, the sensitivity and specificity in the diagnosis of lung cancer were 57.4%and 83.9%. Conclusion The serum level of HE4 is a sensitive and specific tumor marker in lung cancer. There are no significant differences in the serum levels of HE4 between different pathological types and different TNM staging in lung cancer patients. The detection of serum levels of HE4 are useful for the diagnosis of lung cancer.
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Objective To study the clinical value of combined detection of tissue polypeptide antigen(TPA) and human epididymal secretory protein 4 (HE4) in the diagnosis and disease monitoring for ovarian epithelial cancer.Methods 82 cases with epithelial ovarian cancer were enrolled in ovarian cancer group,93 cases with benign ovarian lesions were selected as the benign ovarian lesions group,100 healthy people were selected as the control group.Serum TPA and HE4 were detected by ELISA.Results TPA-positive rates in the ovarian cancer group,benign ovarian lesions group and control group were 70.7％,8.6％ and 2.0％,respectively.The TPA-positive rate of ovarian cancer group was higher than benign ovarian lesions group and control group (x2 =33.69,82.95,all P ＜ 0.01).But the difference was not statistically significant between the benign ovarian lesions group and the control group(x2 =3.80,P ＞ 0.05).HE4 positive rates of the ovarian cancer group,benign ovarian lesions group and control group were 82.9％,11.8％,3.0％.The HE4 positive rate of ovarian cancer group was higher than benign ovarian lesions group and control group (x2 =36.72,78.33,all P ＜ 0.01).But the difference was not statistically significant between the benign ovarian lesions group and the control group(x2 =3.28,P ＞ 0.05).The sensitivity,specificity and accuracy of TPA in the diagnosis of ovarian cancer were 70.7 ％,95.2％,88.7％.The sensitivity,specificity and accuracy of HE4 in the diagnosis of ovarian cancer were 82.9 ％,97.2％,92.8％.Conclusion TPA and HE4 can improve the accuracy of the diagnosis of ovarian cancer.
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The serum specimens were collected from ovarian cancer (n =100),benign ovarian disease (n =69) and healthy women (n =95).The serum levels of HE4 and CA125 were detected.Risk of ovarian maliqnancy algorithm (ROMA) was calculated.Accuracy of prediction was evaluated by the area under receiver operating characteristic curve (ROC-AUC).And validity of prediction was evaluated by sensitivity and specificity.The results showed that the median level of ROMA algorithm was 83.0％,8.9％ and 8.7％ in ovarian cancer,benign ovarian disease and healthy women groups respectively.The difference were statistically significant (all P ＜ 0.01).Compared with benign ovarian disease group,the ROC-AUC of ROMA algorithm was 0.900 in ovarian cancer group.The sensitivity and specificity were 81.0％ and 92.8％ in ovarian cancer group respectively.Thus ROMA algorithm is a useful parameter in risk stratification for ovarian cancer.The diagnostic accuracy of ROMA algorithm is better than that of HE4 and CA125 in ovarian cancer.
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Objective To study the expression ot secreted proteins in aggregated dermal papilla cells (DPCs).Methods DPCs were isolated from human scalp tissue and subjected to primary culture and subculture.Aggregated and non-aggregated DPCs served as the subject of this study.Secreted proteins were prepared from these cells and subjected to two-dimensional polyacrylamide gel electrophoresis.Differentially expressed proteins were screened by the PDQuest image analysis software.Protein spots were digested and identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry,and finally analyzed using the National Center for Biotechnology Information (NCBI) non-redundant (Nr) protein database.Results Two-dimensional electrophoresis maps with good repeatability and high resolution were established.Image analysis of 2-D gels revealed that the average number of detected protein spots was 1 134 ± 52 and 1 078 ± 36 in aggregated and nonaggregated DPCs respectively,and the majority of these protein spots were matched between aggregated and nonaggregated DPCs.Twenty-eight protein spots showed more than 5-fold difference between the two groups of cells,and 10 proteins were preliminarily identified as differentially expressed proteins by peptide-mass fingerprinting.Of these differentially expressed proteins,8 proteins including Rhogdi 1,filamin A,cystatin C,fibronectin,cyclophilin A,procollagen C proteinase enhancer 1,tissue inhibitor of metalloproteinase and tissue inhibitor of metalloproteinase-2 were up-regulated,and 2 proteins including neuropolypeptide h3 and matrix metalloproteinase-3/tissue inhibitor of metalloproteinase-1 complex were down-regulated in aggregated DPCs compared with non-aggregated DPCs.Conclusions Differentially expressed proteins between aggregated and non-aggregated DPCs are mainly implicated in cell signaling pathway,cellular proliferation and differentiation,extracellular matrix synthesis and degradation,and so on.
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Objective To evaluate the values of combined detection of carbohydrate antigen 125(CA125) ,human epididymis gene protein 4(HE4) ,soluble mesothelin related peptides(SMRP) in early diagnosis for ovarian cancer and the high-risk factors of ovari-an cancer .Methods 43 patients with malignant ovarian cancer were served as the malignant group ,54 patients with benign ovarian tumors as the benign group ,45 healthy women as the control group .Roche Cobas 6000 Automatic Electrochemiluminescence Immu-noassay Analyzer and enzyme-linked immunosorbent assay (ELISA) were adopted to detect serum CA125 ,HE4 ,SMRP levels . High-risk factors of ovarian cancer was subject to Logistic regression analysis .Results Serum levels of CA125 ,HE4 and SMRP of patients in malignant group were significantly higher than those in the benign group and the control group (P<0 .01) .The sensitivi-ties of CA125 ,HE4 and SMRP detection alone for ovarian cancer diagnosis were 73 .3% ,82 .8% and 70 .8% ,respectively ,while their specificities were 79 .1% ,87 .4% and 83 .3% ,respectively .The sensitivity and specificity of joint detection of CA 125 ,HE4 , SMRP for ovarian cancer diagnosis were 90 .2% and 79 .3% ,respectively .Logistic regression analysis showed that age at menarche younger than 13 years ,menstrual cycle less than 30 d and irregular menstruation were the high-risk factors of ovarian cancer ,with their odds ratio(OR) of 2 .11[95% confidence interval(CI):1 .09-4 .10 ,1 .91(95% CI:1 .21-3 .10) and 1 .57(95% CI:0 .83-2 .94) .Conclusion CA125 detection combined with HE4 or SMRP can markedly improve the diagnostic sensitivity for ovarian cancer .
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Objective To assess the diagnostic value of human epididymis secretory protein (HE4) versus CA125 for endometrial cancer.Methods Serum HE4 and CA125 levels were measured by enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECLI) in 35 patients with endometrial cancer,48 patients with benign endometrial disorders and 40 healthy controls.The best cutoff value,sensitivity and specificity were calculated with pathological results as golden standard.Receiver operating characteristic curves were plotted,and areaunderthecurve (ROC-AUC) was used to compare diagnostic value of HE4 and CA125.Results The median value in HE4 in endometrial cancer were 51.46 pmol/L,which was significantly higher than in the healthy and benign disorder controls (25.65 pmol/L and 27.92 pmol/L).However,CA125 levels did not show statistically significant difference among the 3 groups.The ROC-AUC of HE4 for discriminating endometrial cancer between healthy controls and benign disorder controls were 0.922 and 0.759,respectively,which showed higher diagnostic value than CA125 (ROC-AUC of 0.590 and 0.457,respectively).HE4 had a specificity/sensitivity of 87.5％ /86.1％ for distinguishing healthy controls from endometrial cancer,and 95.5％ /50％ for differential diagnosis with benign disorders.Conclusions Measurement of HE4 can be used as a tumor marker for diagnosis of endometrial cancer.
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Objective To evaluate the diagnostic value of Human Epididymal Protein 4(HE4) and HE4/Cancer Antigen 125 (CA125) parallel detection for ovarian cancer by meta-analysis.Methods The databases,such as Pubmed,Embase and China National Knowledge Infrastructure (CNKI),were employed to search for the studies related to diagnostic value of HE4 and HE4/CA125 parallel detection for ovarian cancer.The screening,data extraction and quality assessment were conducted in accordance with the inclusion and exclusion criteria by two reviewers independently.The software Meta-disc 1.4 was used to perform meta-analysis and draw the forest plots and the Summary Receiver Operating Characteristic (SROC) curves.The AUCs of HE4,HE4/CA125 parallel detection were detected by Z test.The Egger's regression test was applied to evaluate the publication bias by Stata11.0.Results A total of 14 studies with benign control and/or healthy control were included.In the studies with healthy control.The AUCs of HE4,HE4/CA125 parallel detection were 0.9502 ± 0.0137 and 0.9588 ± 0.0113 respectively,but there was no significant difference between them (Z =0.484,P ＞ 0.05) ;In the studies with benign control.The value of cutoff was the most important cause of heterogeneity.The AUCs of HE4,HE4/CA125 parallel detection were 0.9153 ± 0.0095 and 0.9323 ± 0.0082 respectively,but with no significant difference (Z =1.350,P ＞ 0.05).In the subgroup with cut-off value divided by 150 pmoL/L,the AUCs of HE4,HE4/CA125 parallel detection were 0.9032±0.0174 and 0.9267 ±0.0176 respectively,but there was no significant difference between them (Z =0.950,P ＞ 0.05).Conclusions Both HE4 and HE4/CA125 parallel detection had meaningful values for the diagnosis of ovarian cancer.The detection of HE4 had a higher specificity,while the HE4/CA125 parallel detection had a higher sensitivity.But there was no statistical difference between them in diagnosis value of ovarian cancer.
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Objective To explore the clinical value of combined detection of serum human epididymal secretory protein E4 (HF4) and CA125 in the diagnosis of endometrial carcinoma.Methods From Jan 2010 to Apr 2011,the serum specimens were collected from124 cases of endometrial carcinoma,97 cases of benign disease of uterus and 109 cases of healthy women.HE4 levels in the serum were detected by ELISA,and CA125 levels in the serum were detected by the electro- ehemiluminescent immunoassay.Those results were shown with median level.Accuracy of the diagnosis was evaluated by the area under the receiver operating characteristic curve ( ROC-AUC ).ResultsThe median levels of HE4 and CA125 were 78.09 pmol/L and 33.43 kU/L in serum of endometrial carcinoma group.The median levels of HE4 and CA125 were 46.37 pmol/L and 18.26 kU/L in serum of benign disease of uterus group.The median levels of HE4 and CA125 were 31.75 pmol/L and 12.64 kU/L in serum of healthy women group.The HE4 and CA125 levels in serum of endometrial carcinoma group were significantly higher than those of benign disease of uterus group or healthy women group ( all P ＜ 0.05 ).Compared with that benign disease of uterus group,the ROC-AUC of HE4 and CA125 in endometrial carcinoma group were 0.913 and 0.801,respectively.When the specificity was 95.0％,the sensitivities of HE4,CA125,and combined detection of HF4 and CA125 in endometrial carcinoma group were 41.1％,22.6％ and 46.0％,respectively.The positive rates of HE4 and CA125 were 31％ (27/86) and 12％ (10/86) in stage Ⅰ - Ⅱ of endometrial carcinoma,while the positive rates were 63％ (24/38) and 47％ (18/38) in stage Ⅲ -Ⅳ of endometrial carcinoma,in which there were significant difference between patients in stage Ⅲ - Ⅳ and stage Ⅰ - Ⅱ (P ＜ 0.01 ).ConclusionsThe combined detection of serum HE4 and CA125 is helpful to the diagnosis of endometrial carcinoma.The sensitivity,specificity and early diagnosis of HE4 are better than that of CA125.The positive rates of HF4 and CA125 in endometrial carcinoma are related to the clinical staging.
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OBJECTIVE: Differentiation between benign and malignant ovarian neoplasms is essential for creating a system for patient referrals. Therefore, the contributions of the tumor markers CA125 and human epididymis protein 4 (HE4) as well as the risk ovarian malignancy algorithm (ROMA) and risk malignancy index (RMI) values were considered individually and in combination to evaluate their utility for establishing this type of patient referral system. METHODS: Patients who had been diagnosed with ovarian masses through imaging analyses (n = 128) were assessed for their expression of the tumor markers CA125 and HE4. The ROMA and RMI values were also determined. The sensitivity and specificity of each parameter were calculated using receiver operating characteristic curves according to the area under the curve (AUC) for each method. RESULTS: The sensitivities associated with the ability of CA125, HE4, ROMA, or RMI to distinguish between malignant versus benign ovarian masses were 70.4%, 79.6%, 74.1%, and 63%, respectively. Among carcinomas, the sensitivities of CA125, HE4, ROMA (pre-and post-menopausal), and RMI were 93.5%, 87.1%, 80%, 95.2%, and 87.1%, respectively. The most accurate numerical values were obtained with RMI, although the four parameters were shown to be statistically equivalent. CONCLUSION: There were no differences in accuracy between CA125, HE4, ROMA, and RMI for differentiating between types of ovarian masses. RMI had the lowest sensitivity but was the most numerically accurate method. HE4 demonstrated the best overall sensitivity for the evaluation of malignant ovarian tumors and the differential diagnosis of endometriosis. All of the parameters demonstrated increased sensitivity when tumors with low malignancy potential were considered low-risk, which may be used as an acceptable assessment method for referring patients to reference centers.
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Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Young Adult , Algorithms , /analysis , Ovarian Neoplasms/diagnosis , Proteins/analysis , Referral and Consultation/standards , Biomarkers, Tumor/analysis , Endometriosis/diagnosis , Prospective Studies , Risk Assessment , Sensitivity and SpecificityABSTRACT
Purpose: Biochemical or nucleic acid based diagnostic techniques for MAC infection are unsatisfactory. This study aims to identify and evaluate M. avium secretory protein(s) of diagnostic potential, so as to develop a rapid and simple method for diagnosis of MAC infection. Material and Methods: Initially, a specific protein band of ~80-85 kDa was recognised by differential immunoblotting; which was subjected to anion exchange column chromatography for purification of proteins. After fractionisation using SDS-PAGE and electroelution, blast search was carried out. Further immunoreactivity studies were done with M. avium and Mtb infected mice sera. Clinical utilisation of separated protein was evaluated by conducting indirect ELISA with serum samples from mycobacterial infected patients. Results: A specific 81.6 kDa protein, shown to be catalase-peroxidase protein (KatG) by blast search was separated. Immunoreactivity studies of purified KatG proteins with mice sera confirmed it to be specific for M. avium infection. Indirect ELISA with patient samples further confirmed it to be M. avium infection specific. Conclusion: KatG protein is specifically recognised by MAC patients and can be used as a marker for simple and rapid ELISA based tests for differential diagnosis of M. avium infection.
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Human epididymis gene product 4 (HFA)mRNA highly expressed in oarian cancer tissue and the quantity was associated with the type of the ovarian cancer;The serum HF4 had the same specificity and sensitivity in the early diagnosis of oarian cancer compared with CA125 ,and the HF4 had an advantage over theCA125 in that it was less frequently positive in patients with nonmalignant disease;the combination of HE4 andCA125 yielded higher sensitivity ;The serum tumor marker HFA is an excellent marker for determining responseto treatment and for the detection of early recurrence of disease in patients with epithelial ovarian cancer; HE4 isnot only a serological tumor biomarker but also a target for gene-based therapy of ovarian cancer.
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Objective To investigate the value of human epididymis secretory protein 4 ( HE4 ) combined with CA125 assay in differential diagnosis of endometriosis cyst and ovarian malignant tumor.Methods The level of HE4 and CA125 were measured by enzyme-linked immunosorbent assay (ELISA) in the serum specimens of 46 cases in endometriosis cyst group,36 cases in malignant ovarian tumor group,60 cases in benign ovarian diseases and 50 women in healthy women group.Those results were shown with median level.The normal range were 0-150 pmol/L in HE4 and 0-35 kU/L,which either one was more than the threshold value defined as positive index.The sensitivity of assay was evaluated by receiver operating characteristic (ROC) curve,the relation and value of HE4 or CA125 alone and combination assay in diagnosis of endometriosis was analyzed by Mann-Whitney U test and correlation analysis.Results (1) HE4:the median levels of HE4 were 52.4,51.0,50.0 pmol/L in group of endometriosis,normal control and benign ovarian tumor,which didn't show statistical difference.However,HE4 was 507.5 pmol/L inovarian cancer group,which was significantly higher than those of 3 groups (P < 0.05 ).(2 ) CA125:there were significant different in median level of CA125 was observed as 743.0 kU/L in ovarian cancer,84.9 kU/L in endoemtriosis,15.4 kU/L in benign ovarian disease,and 11.5 kU/L in healthy women (P < 0.05).( 3 ) The single assay:when compared with that in endometriosis group,receiver operating characteristic area under the curve( ROC-AUC) were 0.933 in HE4 alone and 0.821 in CA125 alone assay in ovarian cancer group.The specificity was 95% and the sensitivity was 79.6% and 49.0%.(4) The combination assay:when compared with those in endometriosis group,the ROC-AUC was 0.936,the specificity was 95% and the sensitivity was 81.0% in ovarian cancer.Conclusions Measurement of HE4 could be used in differential diagnosis of endometriosis cyst.And the combination of HE4 and CA125 assay could discriminate ovarian endometriosis cysts from ovarian malignant tumors effectively.
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Objective To evaluate the value of human epididymis secretory protein 4(HE4)and CAl25 in the diagnosis of ovariall malignancy.Methods HF4 and CA125 in the serum specimens of malignant ovarian tumor group(30 cases),benign ovarian diseases(110 cases;45 benign ovarian tumor,57endometriotic diseases and 8 pelvic inflammation were included) and healthy women group( 137 cases)were assayed double blindly . The levels and the diagnosis efficiency of the HE4 and CA125 were analyzed.Results (1) The median levels of HE4 and CA125 were significantly higher in malignant ovarian tumor group (244 pmoi/L and 601 kU/L respectively) than those of the benign ovarian diseases group( 32 pmol/L and 22 kU/L respectively)and healthy women group (32 pmoi/L and 11 kU/L respectively) (P =0. 000-0. 029). The median levels of CA125 were also higher in endometriotic diseases and pelvic inflammation groups(53 and 41 kU/L respectively) than those of benign ovarian tumor group and healthy women group (12 and 11 kU/L respectively;P = 0. 000-0. 031 ). (2) The positive rate of HE4 was lower than that of CA12s in malignant ovarian tumor group ( P = 0. 036 ). HE4 was negative in benign diseases and healthy women groups. But the positive rates of CA125 were 56. 1% and 5/8 respectively in endometriotic diseases and pelvic inflammation groups and there were significant differences compared with HE4( P =0. 000). (3)The HE4 assay had advantage over the CA125 assay in receiver operating characteristic-area under the curve (ROC-AUC) and sensitivity with a specificity of 100% when ovarian malignancy was compared with controls having benign diseases and healthy women, benign tumor or benign diseases groups respectively. The CA125 assay had advantage over the HE4 assay in ROC-AUC and sensitivity with the same specificity when ovarian cancers were compared with controls having healthy women group. (4) Combined assay of HE4 and CA125was better than CA125 alone when ovarian malignancy was compared with controls having any group. (5)Combined assay was better than HE4 alone in ROC-AUC and sensitivity with the same specificity when ovarian cancers were compared with controls having benign diseases and healthy women or healthy women groups. And combined assay was lower in the ROC-AUC and the sensitivity with specificity of 100% than HE4 when ovarian cancers were compared with controls having benign tumors or benign diseases groups respectively. (6) The diagnosis efficiency of the HE4 assay at the level 86 pmol/L determined in ROC curve with controls having benign diseases and healthy women group and at the 95% reference level 50 pmol/L of healthy women or 150 pmol/L recommended by the kit respectively was compared. The sensitivity of 50 pmol/L was 73% higher than 150 pmol/L and 86 pmoi/L, while the specificity and positive predictive value were lower ( P = 0. 002, P = 0. 000 ). The specificity, accuracy and positive predictive value of HE4 assay at the set point of 150 pmol/L and 86 pmol/L were 100%, 96% and 96%. The set point of 86 pmol/L had advantage over 150 pmol/L at the sensitivity of diagnosis, 70% and 63% respectively. But the positive predictive value was 95% lower than 150 pmol/L, being 100%. There was no significant difference( P =0. 883, P = 0. 883 ). Conclusions The specificity of HF4 assay is higher than CA125 assay in the diagnosis of ovarian cancer and HE4 combined with CA125 assay can improve the diagnoses. The set point of 150 pmol/L is advantageous for the accurate diagnosis, while the set point of 86 pmol/L is advantageous for the screening of malignant ovarian cancer.
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Monoclonal antibody (mAb) Tg786 against Toxoplasma gondii has been found to detect a 42-kDa rhoptry protein (ROP6) which showed protease activity and host cell binding characteristics after secretion. Using the mAb, a colony containing a 3'-UTR was probed in a T. gondii cDNA expression library. A full length cDNA sequence of the rhoptry protein was completed after 5'-RACE, which consisted of 1,908 bp with a 1,443 bp ORF. The deduced amino acid sequence of ROP6 consisted of a polypeptide of 480 amino acids without significant homology to any other known proteins. This sequence contains an amino terminal stop transfer sequence downstream of a short neutral sequence, hydrophilic middle sequence, and hydrophobic carboxy terminus. It is suggested that the ROP6 is inserted into the rhoptry membrane with both N- and C-termini.
Subject(s)
Animals , Toxoplasma/enzymology , Protozoan Proteins/genetics , Peptide Hydrolases/genetics , Molecular Sequence Data , Gene Library , Cloning, Molecular , Amino Acid Sequence , 3' Untranslated RegionsABSTRACT
This study describes the characterization of 80 kDa protease showing gelationlytic property among three proteases in the excretory/secretory proteins (ESP) from Toxoplasma gondii. The protease activity was detected in the ESP but not in the somatic extract of RH tachyzoites. This protease was active only in the presence of calcium ion but not other divalent cationic ions such as Cu (2+), Zn (2+), Mg (2+), and Mn (2+), implying that Ca (2+) is critical factor for the activation of the protease. The 80 kDa protease was optimally active at pH 7.5. Its gelatinolytic activity was maximal at 37 degrees C, and significant level of enzyme activity of the protease remained after heat treatment at 56 degrees C for 30 min or 100 degrees C for 10 min. This thermostable enzyme was strongly inhibited by metal chelators, i.e., EDTA, EGTA, and 1, 10-phenanthroline. Thus, the 80 kDa protease in the ESP secreted by T. gondii was classified as a calcium dependent neutral metalloprotease.