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@#Metabolomics reflects the endogenous metabolite changes in organisms through qualitative and quantitative detection of small molecules in biological samples, revealing the metabolic changes during disease development. Metabolomic studies of periodontitis further elucidate the etiology, diagnosis and predictive markers of periodontitis at the levels of metabolites and metabolic pathways. In this paper, the concept and research methods of metabonomics were summarized, and the current status of the metabonomics of saliva and gingival crevicular fluid in the study of periodontitis was reviewed. Previous studies have shown that metabolites such as short-chain fatty acids and amino acids and metabolic pathways such as glutamic acid and pyrimidine metabolism might promote the occurrence of periodontitis, and it was suggested that lactic acid, γ-amino-butyrate, butyric acid and lysophosphatidic acid might be potential diagnostic markers of periodontitis. The metabolomics study of periodontitis still faces challenges such as high heterogeneity of results and fluctuation of metabolites. In the future, its study could be optimized through multicenter prospective studies to provide fresh approaches for the etiology and diagnosis of periodontitis.
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Background: Adriamycin is a broadspectrum, potent, older chemotherapy drug and antineoplastic agent used in the treatment of several cancers such as solid tumours, leukaemias, and lymphomas, playing a major role in cancer chemotherapy. Long-term use of this drug results in congestive heart failure and to overcome this effect dietary squalene intake reduces the adverse effects of adriamycin-mediated cardiotoxicity and cellular oxidative stress. Methods: The current study aims to investigate the cytoprotective effects of dietary squalene supplementation on adriamycin-induced cardiomyopathy in rats in terms of alterations in Troponin T, homocysteine, diagnostic marker enzymes, and cardiac tissue histology. Results: The findings show that a 1.5 percent dose of dietary squalene supplementation for 21 days reduced adriamycin-induced changes in homocysteine, troponin T, diagnostic marker enzymes, and lesions in cardiac tissues. Conclusion: The outcomes of the study specified squalene's cytoprotective action which stabilizes membranes against adriamycin-induced oxidative membrane degradation, which is primarily responsible for heart cell irreversible necrosis.
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Imaging and serological approaches play an important role in the diagnosis and treatment of alveolar echinococcosis; however, they also suffer from some problems during their applications in clinical practices, which urges the identification of potential diagnostic markers. Novel serological, genomics and proteomics diagnostic markers alone or in combination may increase the sensitivity and specificity in early diagnosis of alveolar echinococcosis, which play vital roles in monitoring of disease courses and prognostic evaluation. This review mainly presents the advances in the studies on novel diagnostic markers for alveolar echinococcosis.
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MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules whose role in breast cancer has been gradually discovered and clinically recognized and valued. MiRNAs play a role in the regulation of related target genes and signaling pathways in breast cancer, and participate in the proliferation, apoptosis, invasion and metastasis of breast cancer cells, and have new biomarker potential in clinical diagnosis and prognosis of breast cancer. It provides new ways and methods for the clinical treatment of breast cancer, and has important value and application prospects in reducing drug resistance and enhancing drug sensitivity. This article reviews the research progress of miRNAs in the molecular mechanism, clinical diagnosis, prognosis and clinical target treatment of breast cancer, and puts some suggestions and forward for future research directions.
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MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules whose role in breast cancer has been gradually discovered and clinically recognized and valued. MiRNAs play a role in the regulation of related target genes and signaling pathways in breast cancer, and participate in the proliferation, apoptosis, invasion and metastasis of breast cancer cells, and have new biomarker potential in clinical diagnosis and prognosis of breast cancer. It provides new ways and methods for the clinical treatment of breast cancer, and has important value and application prospects in reducing drug resistance and enhancing drug sensitivity. This article reviews the research progress of miRNAs in the molecular mechanism, clinical diagnosis, prognosis and clinical target treatment of breast cancer, and puts some suggestions and forward for future research directions.
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MicroRNA(miRNA)is a class of non-coding,endogenous RNA molecules.It has been confirmed in many studies that miRNA has aberrant expression in human tumors,which is related to the occurrence,progression and the response to treatment of various human tumors.MicroRNA-7(miR-7)is an important member of the miRNA family.Recent studies have reported that miR-7 is closely related to the occurrence,development,treatment and prognosis of endocrine malignant tumors such as thyroid cancer and pan -creatic cancer,indicating that it may serve as a potential molecular target for biological treatment of endocrine malignancies.The re-search progression in the relationship between miR-7 and thyroid cancer,as well as other endocrine malignant tumors are reviewed in this paper.
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Hepatitis B core antibody (anti-HBc) targets viral core protein and is produced in patients with hepatitis B virus (HBV) infection, and seroconversion occurs in the early stage of infection and often lasts for a lifetime. Qualitative detection of anti-HBc has been used in clinical practice for many years, while the clinical significance of its quantitative level remains unclear. A novel anti-HBc immunoassay based on double-antigen sandwich ELISA has been developed in recent years and lays a foundation for illustrating the change in the quantitative level of anti-HBc (qAnti-HBc) in HBV infection and its clinical significance. Several recent studies have revealed that qAnti-HBc is associated with the degree of hepatitis activity and response to pharmacotherapy and may become an important basis for selecting antiviral drugs, optimizing therapeutic regimen, and predicting treatment outcome.
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PURPOSE: Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. MATERIALS AND METHODS: A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. RESULTS: Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. CONCLUSION: Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.
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Aged , Female , Humans , Male , Middle Aged , Biomarkers/metabolism , Carcinoma, Transitional Cell/genetics , Carnitine/analogs & derivatives , Case-Control Studies , Metabolic Networks and Pathways/physiology , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Urinary Bladder Neoplasms/geneticsABSTRACT
Objective To investigate the predictive value of 4 183 Da peptide of dermcidin protein in the early diagnosis and differential diagnosis of ischemic heart disease.Methods A prospective controlled study was conducted.Serum samples were drawn from 161 patients with acute coronary syndrome [ACS,including 46 patients with unstable angina (UA),23 with acute non-ST elevation myocardial infarction,and 92 with acute ST segment elevation myocardial infarction],111 subjects for routine physical examination,including 45 patients with hypertension history,42 with coronary heart disease,22 with diabetes,and 54 patients with non-ACS (including pulmonary embolism,aortic dissection aneurysm,arrhythmia,myocarditis,coronary myocardial bridge,pleurisy,pneumothorax,pneumomediastinum,rib fracture,reflux esophagitis,peptic ulcer,and pancreatitis) to serve as controls.4 183 Da peptide of dermcidin protein was assessed with matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) technology,and myeloperoxidase [MPO,determined by point-of-care testing (POCT) and enzyme linked i mmunosorbent assay (ELISA),respectively],high sensitive C-reactive protein (hs-CRP),heart type fatty acid binding protein (H-FABP),myoglobin (MYO),cardiac troponin Ⅰ (cTnⅠ),and MB isoenzyme of creatine kinase (CK-MB) were quantitated with biochemical analysis.The power of the biomarkers above for early diagnosis and differential diagnosis for ischemic heart disease were judged by comparison of their sensitivity and specificity.Results ① It was showed by one-way ANOVA that 4 183 Da peptide was higher in ACS group than that in control group (relative abundance:22.05 ± 16.97 vs.15.52 ± 14.09,P =0.001),but no difference was found between ACS group and non-ACS group (relative abundance:22.05 ± 16.97 vs.19.99 ± 17.63,P =0.416).② The specificity and sensitivity of the 4 183 Da polypeptide and MPO for predicting ACS and UA were compared with the receiver operating characteristic curve (ROC).It was showed that the 4 183 Da polypeptide had predictive values for ACS and UA,and the areas under the ROC curve (AUC) was 0.625 and 0.651 (both P ＜ 0.01),but MPO was not found to have predictive value (AUC was 0.440 and 0.336,respectively,both P ＞ 0.05).③ It was showed by the values of multi-markers in differential diagnosis of ACS and non-ACS disease that the specificity and sensitivity of 4 183 Da peptide in the differential diagnosis of acute myocardial infarction (AMI) and non-ACS disease were less than those of MYO,cTnⅠ,H-FABP,markers of myocardial damage,which AUCs were 0.569 vs.0.796,0.833,0.838,and equal to MPO (POCT/ELISA) and hs-CRP,AUC of which was 0.569 vs.0.505 (POCT)/0.477 (ELISA) and 0.545.But both the value of 4 183 Da peptide and MYO,cTnⅠ,H-FABP in the differential diagnosis of UA and non-ACS disease was not found,where AUC was 0.456,0.525,0.658,0.568.Conclusion 4 183 Da polypeptide,a fragment of dermcidin protein,may have association with the onset of ischemic heart disease,and may be helpful in the early diagnosis of ACS.
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The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.
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Aged , Aged, 80 and over , Humans , Male , Middle Aged , Biomarkers, Tumor/genetics , Calgranulin B/genetics , Cohort Studies , Nucleic Acids/genetics , Oligonucleotide Array Sequence Analysis , Prostate/metabolism , Prostatic Hyperplasia/diagnosis , Prostatic Neoplasms/diagnosis , RNA, Messenger/genetics , RNA, Neoplasm/genetics , ROC Curve , Real-Time Polymerase Chain Reaction , Tetraspanins/geneticsABSTRACT
Objective To detect the expressions and clinical significance of Nanog and CD44 protein in lung cancer. Methods The expressions of Nanog and CD44 were detected by immunohistochemistry in 50 cases of lung cancer, 32 cases of benign lesion lung tissue and 18 cases of paraneoplastic normal lung tissue. Then their relationships with clinicopathological factors were analyzed. Results The expression of Nanog in lung cancer was significantly higher than those in benign lesion lung tissue and paraneoplastic normal lung tissue (P 0.05). The expressions of Nanog and CD44 in squamous cell carcinomas were higher than those in adenocarcinomas and small cell lung carcinomas (P 0.05). The positive correlation was also noted between the expressions of Nanog and CD44 in lung cancer (r = 0.564, P < 0.05). Conclusion Nanog and CD44 proteins may participate in the genesis and progression of lung cancer. Nanog protein is a potential diagnostic marker and therapeutic target for lung cancer.
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Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.
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Animals , Humans , Mice , Acrolein , Biomarkers , Brain Infarction , C-Reactive Protein , Diacetyl , DNA , Early Detection of Cancer , Eukaryotic Cells , Hydrogen Peroxide , Inflammation , Interleukin-6 , Lysine , Metabolism , Oxidative Stress , Oxidoreductases , Phospholipids , Plasma , Polyamines , Putrescine , Renal Insufficiency , RNA , Sensitivity and Specificity , Spermidine , Spermine , StrokeABSTRACT
Context : To evaluate the usefulness of urinary albumin excretion rate (UAER) i.e. Albumin/Creatinine Ratio (ACR) in diagnosis and prognosis of essential hypertension (EHT). Objectives : To find out the association of urinary albumin excretion rate with the pathophysiology of essential hypertension. Study Design : A cross-sectional analytical study. Materials & Methods : Urinary albumin excretion (UAE), urinary creatinine (UC) and UAER were analyzed and compared between hypertensive cases and age & sex matched normotensive controls of age group 30-65 years using unpaired two-tailed Student ‘t’ test. All statistical analyses were done with PASW (SPSS) v.18.0. Results : Systolic BP (SBP) and diastolic BP (DBP) of cases were found to be significantly higher (p < 0.001) than controls. Urine MAlb level (p < 0.001) and ACR (p < 0.001) in cases were significantly higher compared to controls. Correlation studies showed that SBP and DBP was significantly positively correlated with urine MAlb (SBP: r = 0.859, DBP: r = 0.733; p < 0.001) and ACR (SBP: r = 0.830, DBP: r = 0.739; p < 0.001). Sex-wise comparison in cases revealed that males had statistically non-significant (p > 0.05) lower levels of urine MAlb as compared to females but had significantly higher (p < 0.001) levels of urine creatinine and lower (p < 0.001) ACR compared to females. Conclusion: Urinary MAlb levels and ACR are seen to be increased in hypertensive subjects compared to normotensive subjects. ACR was significantly higher in female hypertensives than males which can be credited to the physiologically observed lower urine creatinine levels compared to males. Both Microalbuminuria and ACR can serve as specific and well-established marker of cardiovascular and renal damage in EHT.
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Adult , Albumins/diagnosis , Albumins/metabolism , Creatinine/metabolism , Creatinine/urine , Female , Humans , Hypertension/diagnosis , Hypertension/urine , Male , Middle Aged , Prognosis , Renal EliminationABSTRACT
Objective: To assess the levels of adenosine deaminase (ADA) in serum in patients with sputum smear negative pulmonary tuberculosis (SNPTB) and to compare it with serum ADA levels in patients with non-tuberculous pulmonary disease - chronic obstructive pulmonary disease (COPD) and with healthy control group and to explore its validity as a diagnostic marker in serum in SNPTB patients.Methods:Three groups of study populations were made. Group I: SNPTB - 142 cases, Group II:non-tubercular pulmonary disease - COPD - 40 cases, Group III: healthy controls - 80 cases. Serum samples were collected and ADA assay was done by the method of Guisti and Galanti. Results: ADA levels (Mean±SD, U/L) in the three groups were as follows: Group I: 42.26±21.22, Group II: 23.31±8.22, Group III: 18.88±6.67. Difference between Group I and Group III was statistically significant (P < 0.0001). The test showed a high specificity 91.25% (95% confidence interval - CI 83.00 - 95.7) and a sensitivity of 83.10% (95% CI 76.08-88.37) in Group I. Positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and accuracy in Group I were 94.00%, 69.52%, 9.49, 0.18 and 82.43% respectively.Conclusions: Overall assessment of the use of serum ADA levels as a diagnostic biochemical marker in smear-negative pulmonary tuberculosis patients showed promising results. Studies with a larger population group are required to validate its use as a routine diagnostic test in these cases.
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<b>Background:</b> Rapid and accurate diagnosis is essential for containing the novel influenza A/H1N1 pandemic. Polymerase chain reaction (PCR) testing is an accurate diagnostic method, but it is not routinely available worldwide. We herein evaluated the usefulness of pharyngeal “influenza follicles” in diagnosing seasonal influenza and influenza A/2009 (H1N1) pdm.<br><b>Methods:</b> Between August 3 and October 29, 2009, we evaluated 87 patients with influenza-like symptoms. Twenty-three had influenza follicles (22 on initial evaluation; 1 on follow-up) while 64 did not. Considering these two groups, we then compared the positive cases using rapid diagnostic testing (confirmed by PCR). In addition, 419 cases of seasonal influenza diagnosed between 2003 and 2009 were examined for the presence of influenza follicles based on Miyamoto's 2007 definition<sup>9</sup>, and new exclusion criteria were developed.<br><b>Results:</b> Among the 23 patients with influenza follicles, 21 were diagnosed with novel influenza. Of these, follicles were present on initial evaluation in 20 and on follow-up in 1. None of the 64 patients without influenza follicles were diagnosed with influenza (sensitivity 100%, specificity 97%). Among the 419 patients diagnosed with seasonal influenza between 2003 and 2009, influenza follicles occurred in all type A/H3N2, A/H1N1, and B cases (sensitivity 95.46%, specificity 98.42%). Thus, follicles were considered a specific sign of influenza.<br><b>Conclusion:</b> Influenza follicles occur in both seasonal and novel influenza. This identification method has higher diagnostic sensitivity and specificity than rapid diagnostic testing and is a promising clinical tool for diagnosing influenza when PCR is unavailable, or in pandemic situations.
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Objective To identify genes associated with hepatocellular carcinoma (HCC) as candidate diagnostic markers in a genome-wide scale. Methods The gene expression profiles of 40 pairs of HCC tumor tissue and peripheral non-tumorous liver tissue were analyzed by using gene chip technology.The gene chips were fabricated at the National Cancer Institute (NCI). Each gene chip contained 9 180 genes. The fluorescent targets were prepared by a direct labeling approach using two kinds of fluorescences as following: 100 ?g of total RNA from non-cancerous liver tissue was labeled with Cy3-dUTP and 200 ?g of total RNA from HCC was labeled with Cy5-dUTP. The targets were mixed together and hybridized with genes on the gene chips. Unsupervised hierarchical clustering analysis was done by CLUSTER and TREEVIEW software using median centered correlation and complete linkage. Results A total of 10 genes were found up-regulated in over 80% of primary tumors comparing with that of their corresponding non-tumorous liver tissues at a two-fold filter with an unsupervised hierarchical clustering algorithm, including protocadherin-alpha 9, ESTs, Homo sapiens cDNA FLJ, KPNA2, RPS20, SNRPE, CDKN2A, UBD, MDK and ANXA2. Conclusion These genes are supposed to be candidates for the diagnosis of HCC. Further investigation of these genes in a large scale of patients with HCC and patients with non-malignant hepatic diseases will be needed to disclose whether they could be used clinically as novel diagnostic tumor markers for HCC.
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BACKGROUND/AIMS: NAD glycohydrolase (NADase) is abundantly expressed in the liver. This expression is prominent in Kupffer cells. Since it was recognized that reticulendothelial function is impaired in liver cirrhosis, we assessed how these enzyme activities were altered in patients with liver cirrhosis. METHODS: Serum samples were obtained from 61 patients with liver cirrhosis (according to the criteria of Child-Pugh 15 were classified A, 24 were classified B, and 22 were classified C) and 16 healthy subjects. NADase activities were measured fluorometrically with [adenine-14C] NAD. The reaction mixture contained [adenine-14C] NAD and enzyme (patient serum). The reaction was stopped after a 30 to 480 min incubation by the addition of 50 L of 25% trichloroacetic acid. RESULTS: Serum NADase activities in 61 patients with liver cirrhosis were significantly lower than those in healthy subjects (33+/-14 vs. 55.6+/-13 p<0.001). Serum NADase activities in severe cirrhotic patients were significantly lower than those in mild to moderate cirrhotic patients (criteria of Child-Pugh, A: 40.6+/-6.4 vs. B: 38.6+/-13 vs. C: 21.8+/-14, p<0.001). NADase activities were correlated to prothrombin time (r = 0.69), and Apo A1 (r = 0.58) that were useful in identifying high-risk subjects for severe liver disease, but not asparate aminotransferase (AST) and alanine aminotransferase (ALT). Also, NADase activities reciprocally correlated with PGAA index (r = -0.78), Child-Pugh's score (r = -0.48), and serum alpha-2-macroglobulin (r = -0.72). CONCLUSIONS: NADase activities could be used as a single diagnostic marker for liver cirrhosis in addition to the Child-Pugh's score and PGAA index.
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Humans , Alanine Transaminase , Apolipoprotein A-I , Kupffer Cells , Liver Cirrhosis , Liver Diseases , Liver , NAD , NAD+ Nucleosidase , Prothrombin Time , Trichloroacetic AcidABSTRACT
PURPOSE: The detection of telomerase activity is a new and useful method in diagnosis of bladder transitional cell carcinoma(TCC) in urine samples. But the detection method of telomerase activity is not easily performed in clinical settings because it uses radio-isotope and electrophoresis. We evaluated the test results of telomerase PCR-ELISA and compared them with the results of urinary cytology. MATERIALS AND METHODS: In order to evaluate the feasibility of telomerase PCR-ELISA method in bladder TCC, 36 bladder washing samples of patients with bladder TCC and 10 bladder washing samples of benign urologic diseases were examined for telomerase activity. RESULTS: The overall sensitivity and specificity of the telomerase test was 76.5%(26/36) and 80.0%(4/5). The sensitivity of telomerase test was higher than that of urinary cytology in low grade bladder TCC. Sensitivity of the telomerase test according to the nuclear grade of bladder TCC was 61.5% in grade I, 92.3% in grade II, 75% in grade III. In contrast, the sensitivity was 38.5% in grade I, 66.7% in grade II, 87.5% in grade III in urinary cytology. There was no correlation between the tumor stages and the sensitivity of telomerase test. CONCLUSIONS: We have shown that the sensitivity and specificity of telomerase PCR-ELISA method is similar to the results of telomerase tests previously reported using radioisotope. Furthermore, the telomerase test is more sensitive in detecting bladder tumor of low grade than urinary cytology. These findings suggest that telomerase PCR-ELISA method can be used conveniently and widely for the detection of bladder tumor in clinical practice.