Highly Sensitive and Cost-Effective Portable Sensor for Early Gastric Carcinoma Diagnosis

Facile and efficient early detection of cancer is a major challenge in healthcare. Herein we developed a novel sensor made from a polycarbonate (PC) membrane with nanopores, followed by sequence-specific Oligo RNA modification for early gastric carcinoma diagnosis. In this design, the gastric cancer antigen CA72-4 is specifically conjugated to the Oligo RNA, thereby inhibiting the electrical current through the PC membrane in a concentration-dependent manner. The device can determine the concentration of cancer antigen CA72-4 in the range from 4 to 14 U/mL, possessing a sensitivity of 7.029 µAU−1mLcm−2 with a linear regression (R2) of 0.965 and a lower detection limit of 4 U/mL. This device has integrated advantages including high specificity and sensitivity and being simple, portable, and cost effective, which collectively enables a giant leap for cancer screening technologies towards clinical use. This is the first report to use RNA aptamers to detect CA72-4 for gastric carcinoma diagnosis.

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Inhibition of Cytochrome P450 (CYP450) Isoforms by Isoniazid: Potent Inhibition of CYP2C19 and CYP3A

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.2.382-392.2001 ◽

2001 ◽

Vol 45 (2) ◽

pp. 382-392 ◽

Cited By ~ 112

Author(s):

Zeruesenay Desta ◽

Nadia V. Soukhova ◽

David A. Flockhart

Keyword(s):

Cytochrome P450 ◽

Liver Microsomes ◽

Cost Effective ◽

Competitive Inhibitor ◽

Inhibitory Effect ◽

Significant Inhibition ◽

Specific Substrate ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

The Mean

ABSTRACT Isoniazid (INH) remains the most safe and cost-effective drug for the treatment and prophylaxis of tuberculosis. The use of INH has increased over the past years, largely as a result of the coepidemic of human immunodeficiency virus infection. It is frequently given chronically to critically ill patients who are coprescribed multiple medications. The ability of INH to elevate the concentrations in plasma and/or toxicity of coadministered drugs, including those of narrow therapeutic range (e.g., phenytoin), has been documented in humans, but the mechanisms involved are not well understood. Using human liver microsomes (HLMs), we tested the inhibitory effect of INH on the activity of common drug-metabolizing human cytochrome P450 (CYP450) isoforms using isoform-specific substrate probe reactions. Incubation experiments were performed at a single concentration of each substrate probe at its Km value with a range of INH concentrations. CYP2C19 and CYP3A were inhibited potently by INH in a concentration-dependent manner. At 50 μM INH (∼6.86 μg/ml), the activities of these isoforms decreased by ∼40%. INH did not show significant inhibition (<10% at 50 μM) of other isoforms (CYP2C9, CYP1A2, and CYP2D6). To accurately estimate the inhibition constants (Ki values) for each isoform, four concentrations of INH were incubated across a range of five concentrations of specific substrate probes. The meanKi values (± standard deviation) for the inhibition of CYP2C19 by INH in HLMs and recombinant human CYP2C19 were 25.4 ± 6.2 and 13 ± 2.4 μM, respectively. INH showed potent noncompetitive inhibition of CYP3A (Ki = 51.8 ± 2.5 to 75.9 ± 7.8 μM, depending on the substrate used). INH was a weak noncompetitive inhibitor of CYP2E1 (Ki = 110 ± 33 μM) and a competitive inhibitor of CYP2D6 (Ki = 126 ± 23 μM), but the mean Ki values for the inhibition of CYP2C9 and CYP1A2 were above 500 μM. Inhibition of one or both CYP2C19 and CYP3A isoforms is the likely mechanism by which INH slows the elimination of coadministered drugs, including phenytoin, carbamazepine, diazepam, triazolam, and primidone. Slow acetylators of INH may be at greater risk for adverse drug interactions, as the degree of inhibition was concentration dependent. These data provide a rational basis for understanding drug interaction with INH and predict that other drugs metabolized by these two enzymes may also interact.

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Respiratory Tularemia: Francisella Tularensis and Microarray Probe Designing

The Open Microbiology Journal ◽

10.2174/1874285801610010176 ◽

2016 ◽

Vol 10 (1) ◽

pp. 176-182 ◽

Cited By ~ 8

Author(s):

Reza Ranjbar ◽

Payam Behzadi ◽

Caterina Mammina

Keyword(s):

Dna Microarray ◽

Francisella Tularensis ◽

High Specificity ◽

Cost Effective ◽

High Rate ◽

Molecular Diagnostic ◽

Microarray Technology ◽

Microarray Probe ◽

Specificity And Sensitivity ◽

Oligo Microarray

Background:Francisella tularensis(F. tularensis) is the etiological microorganism for tularemia. There are different forms of tularemia such as respiratory tularemia. Respiratory tularemia is the most severe form of tularemia with a high rate of mortality; if not treated. Therefore, traditional microbiological tools and Polymerase Chain Reaction (PCR) are not useful for a rapid, reliable, accurate, sensitive and specific diagnosis. But, DNA microarray technology does. DNA microarray technology needs to appropriate microarray probe designing.Objective:The main goal of this original article was to design suitable long oligo microarray probes for detection and identification ofF. tularensis.Method:For performing this research, the complete genomes ofF. tularensissubsp.tularensisFSC198,F. tularensissubsp.holarcticaLVS,F. tularensissubsp.mediasiatica,F. tularensissubsp.novicida(F. novicidaU112), andF. philomiragiasubsp.philomiragiaATCC 25017 were studiedviaNCBI BLAST tool, GView and PanSeq Servers and finally the microarray probes were produced and processedviaAlleleID 7.7 software and Oligoanalyzer tool, respectively.Results:In thisin silicoinvestigation, a number of long oligo microarray probes were designed for detecting and identifyingF. tularensis. Among these probes, 15 probes were recognized as the best candidates for microarray chip designing.Conclusion:Calibrated microarray probes reduce the biasis of DNA microarray technology as an advanced, rapid, accurate and cost-effective molecular diagnostic tool with high specificity and sensitivity. Professional microarray probe designing provides us with much more facility and flexibility regarding preparation of a microarray diagnostic chip.

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The Use of Biomarkers in Early Diagnostics of Pancreatic Cancer

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2018/5389820 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Lumir Kunovsky ◽

Pavla Tesarikova ◽

Zdenek Kala ◽

Radek Kroupa ◽

Petr Kysela ◽

...

Keyword(s):

Radical Surgery ◽

Early Stage ◽

Locally Advanced ◽

High Specificity ◽

Cost Effective ◽

Ductal Adenocarcinoma ◽

Specificity And Sensitivity ◽

Solid Malignancies ◽

Late Detection ◽

Resistance To Chemotherapy

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies with increasing incidence. The poor prognosis is due to the aggressive nature of the tumor, late detection, and the resistance to chemotherapy and radiotherapy. A radical surgery procedure is the only treatment that has been shown to improve the 5-year survival rate to 20-25%. However, the majority of patients (80-85%) are diagnosed with locally advanced or metastatic disease and just 15-20% patients are diagnosed in an early stage allowing them to undergo the potentially curative surgical resection. The early detection of PDAC without the use of invasive methods is challenging and discovery of a cost-effective biomarker with high specificity and sensitivity could significantly improve the treatment and survival in these patients. In this review, we summarize current and newly examined biomarkers in early PDAC detection.

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Correlation of fine needle aspiration cytology and histopathology of neck swellings

International Journal of Otorhinolaryngology and Head and Neck Surgery ◽

10.18203/issn.2454-5929.ijohns20180986 ◽

2018 ◽

Vol 4 (3) ◽

pp. 648

Author(s):

C. S. Asha ◽

B. R. Suchit Roy

Keyword(s):

Salivary Gland ◽

Lymph Node ◽

Predictive Value ◽

Age Groups ◽

Invasive Procedure ◽

High Specificity ◽

Cost Effective ◽

Needle Aspiration ◽

Predictive Values ◽

Specificity And Sensitivity

Background: Neck swellings are a common clinical finding affecting all age groups. FNAC is a minimally invasive procedure helpful in the diagnosis of various neck swellings. The purpose of this study is to determine the accuracy of FNAC in the diagnosis of neck swellings by comparing it with the histopathology which is taken as the gold standard.Methods: A prospective study which included 90 patients who attended ENT and surgery departments of Government Medical College, Trivandrum with neck swellings from July 2006-2007. FNAC of the swelling was done and the FNAC results were compared with the histopathology results. The specificity, sensitivity, positive and negative predictive values and accuracy of FNAC were calculated. Results: Of the 90 patients, thyroid swelling formed the major group followed by lymph node, salivary gland and miscellaneous swellings. Thyroid swellings had a female predominance while the other three groups namely lymph node, salivary gland and miscellaneous groups showed a male preponderance. When the neck swellings namely thyroid, salivary gland, lymph node and miscellaneous group were taken into consideration as a whole, the sensitivity of FNAC for detecting malignancy was 64.3%. The specificity, positive predictive value, negative predictive value and accuracy were 97.4%, 81.8%, 93.7% and 92% respectively.Conclusions: FNAC can be rated as a safe, simple, reliable, cost effective and rapid diagnostic tool with high specificity and sensitivity for the initial evaluation of neck swellings.

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Glycoprotein- and Lectin-Based Approaches for Detection of Pathogens

Pathogens ◽

10.3390/pathogens9090694 ◽

2020 ◽

Vol 9 (9) ◽

pp. 694

Author(s):

Sammer-ul Hassan ◽

Ahmed Donia ◽

Usman Sial ◽

Xunli Zhang ◽

Habib Bokhari

Keyword(s):

Infectious Diseases ◽

Point Of Care ◽

Healthcare Providers ◽

Basic Research ◽

High Specificity ◽

Cost Effective ◽

Emerging Diseases ◽

Public Healthcare ◽

Point Of Use ◽

Specificity And Sensitivity

Infectious diseases alone are estimated to result in approximately 40% of the 50 million total annual deaths globally. The importance of basic research in the control of emerging and re-emerging diseases cannot be overemphasized. However, new nanotechnology-based methodologies exploiting unique surface-located glycoproteins or their patterns can be exploited to detect pathogens at the point of use or on-site with high specificity and sensitivity. These technologies will, therefore, affect our ability in the future to more accurately assess risk. The critical challenge is making these new methodologies cost-effective, as well as simple to use, for the diagnostics industry and public healthcare providers. Miniaturization of biochemical assays in lab-on-a-chip devices has emerged as a promising tool. Miniaturization has the potential to shape modern biotechnology and how point-of-care testing of infectious diseases will be performed by developing smart microdevices that require minute amounts of sample and reagents and are cost-effective, robust, and sensitive and specific. The current review provides a short overview of some of the futuristic approaches using simple molecular interactions between glycoproteins and glycoprotein-binding molecules for the efficient and rapid detection of various pathogens at the point of use, advancing the emerging field of glyconanodiagnostics.

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Steroid inhibition of calcitriol-induced prolactin production in GH4C1 cells. Specificity and sensitivity

Biochemical Journal ◽

10.1042/bj2410397 ◽

1987 ◽

Vol 241 (2) ◽

pp. 397-401 ◽

Cited By ~ 2

Author(s):

J D Wark ◽

V Gurtler

Keyword(s):

Pituitary Tumour ◽

Dependent Manner ◽

Hormone Production ◽

Concentration Dependent Manner ◽

Dihydroxyvitamin D3 ◽

Specificity And Sensitivity ◽

Rat Pituitary ◽

Increased Sensitivity ◽

Ic50 Concentration ◽

Glucocorticoid Effect

The induction of prolactin (PRL)-gene expression by calcitriol (1,25-dihydroxyvitamin D3, 1,25-dihydroxycholecalciferol) in clonal rat pituitary tumour (GH4C1) cells was selectively inhibited by cortisol [IC50 (concentration causing 50% inhibition) = 3.2-4.1 nM]. The steroid specificity of this effect was investigated and various steroids were found to inhibit calcitriol-stimulated PRL production with the following relative potencies: cortisol, 1; dexamethasone, 8; 11-deoxycortisol, 0.5; corticosterone, 0.4; aldosterone, 0.07; testosterone and oestradiol, less than 0.003. The steroid antagonist RU 38486 did not affect basal or calcitriol-stimulated PRL production, but antagonized the effect of 10 nM-cortisol in a concentration-dependent manner. Neither progesterone nor 11-deoxycortisol antagonized the effect of 10 nM-cortisol. Calcitriol-induced PRL production was 14 times more sensitive to dexamethasone inhibition than was non-stimulated PRL production. Growth-hormone production was stimulated by dexamethasone, in the presence or absence of calcitriol, with a concentration-dependence similar to that of dexamethasone inhibition of basal PRL production. These data indicate that steroid inhibition of calcitriol-stimulated PRL production is a specific glucocorticoid effect. The sensitivity of calcitriol-stimulated PRL production to dexamethasone was 14-26-fold greater than that of other measured responses in the same cells. Two of the possible explanations for this selectively increased sensitivity to glucocorticoids are: amplification of the glucocorticoid effect via an induced mediator; and the presence of very-high-affinity glucocorticoid-receptor-binding sites on DNA.

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Concurrent and Convergent Validity of a Single, Brief Question for Physical Activity Assessment

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17061989 ◽

2020 ◽

Vol 17 (6) ◽

pp. 1989 ◽

Cited By ~ 1

Author(s):

Antonio Moreno-Llamas ◽

Jesús García-Mayor ◽

Ernesto De la Cruz-Sánchez

Keyword(s):

Physical Activity ◽

Convergent Validity ◽

High Specificity ◽

Cost Effective ◽

Classification Performance ◽

Short Version ◽

Operating Characteristics ◽

Time Saving ◽

Physically Active ◽

Specificity And Sensitivity

An extensive number of self-reported methods for physical activity (PA) measurement are available, including short and long recall questionnaires ranging from a few to tens of questions. Due to the fact that simple, time-saving methods could be more practical and desirable for use in a busy clinical context, as well as in public health surveys, we evaluated how a single-item question might be a useful and cost-effective method for assessing compliance with PA guidelines. Using multiple receiver operating characteristics (ROC), we assessed the classification performance of a single brief question, employing the short version of the International Physical Activity Questionnaire as criterion instrument, in a total of 55,950 people (30,601 women and 25,349 men). Both those who practice PA almost daily and a few times a week presented an upper threshold (1042.5 metabolic equivalent minutes (MET) minutes/week) to the established compliance PA guidelines (600 MET minutes/week) with high specificity and sensitivity, using a sedentary group as reference. Otherwise, the occasionally physically active group did not reach the minimum (349.5 MET minutes/week) and obtained a poorer classification performance. A single brief question is a pragmatic and alternative method for assessment of compliance with PA guidelines.

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A LAMP at the end of the tunnel: a rapid, field deployable assay for the kauri dieback pathogen,Phytophthora agathidicida

10.1101/793844 ◽

2019 ◽

Author(s):

Richard C. Winkworth ◽

Briana C.W. Nelson ◽

Stanley E. Bellgard ◽

Chantal M. Probst ◽

Patricia A. McLenachan ◽

...

Keyword(s):

Hybrid Approach ◽

Lamp Assay ◽

High Specificity ◽

Cost Effective ◽

Direct Evaluation ◽

Term Survival ◽

Apocytochrome B ◽

Specificity And Sensitivity ◽

Laboratory Facility ◽

Assay Performance

AbstractThe collar rot causing oomycete,Phytophthora agathidicida, threatens the long-term survival of the iconic New Zealand kauri. Currently, testing for this pathogen involves an extended soil bioassay that takes 14-20 days and requires specialised staff, consumables, and infrastructure. Here we describe a loop-mediated isothermal amplification (LAMP) assay for the detection ofP. agathidicidathat targets a portion of the mitochondrial apocytochrome b coding sequence. This assay has high specificity and sensitivity; it did not cross react with a range of otherPhytophthoraisolates and detected as little as 1 fg of totalP. agathidicidaDNA or 116 copies of the target locus. Assay performance was further investigated by testing plant tissue baits from flooded soil samples using both the extended bioassay and LAMP testing of DNA extracted from baits. In these comparisons,P. agathidicidawas detected more frequently using the LAMP assay. In addition to greater sensitivity, by removing the need for culturing, the hybrid baiting plus LAMP approach is more cost effective than the bioassay and, importantly, does not require a centralised laboratory facility with specialised staff, consumables, and equipment. Such testing will allow us to address outstanding questions aboutP. agathidicida. For example, the hybrid approach could enable monitoring of the pathogen beyond areas with visible disease symptoms, allow direct evaluation of rates and patterns of spread, and allow the effectiveness of disease control to be evaluated. The hybrid assay also has the potential to empower local communities. These communities could use this diagnostic tool to evaluate the pathogen status of local kauri stands, providing information around which to base their management and allowing informed engagement with wider initiatives.

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A peptide mimetic of the mycobacterial mannosylated lipoarabinomannan: characterization and potential applications

Journal of Medical Microbiology ◽

10.1099/jmm.0.46920-0 ◽

2007 ◽

Vol 56 (5) ◽

pp. 579-586 ◽

Cited By ~ 18

Author(s):

Ayelet Barenholz ◽

Avi-Hai Hovav ◽

Yolanta Fishman ◽

Galia Rahav ◽

Jonathan M. Gershoni ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Phage Display ◽

Peptide Libraries ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Keyhole Limpet Haemocyanin ◽

Peptide Epitope ◽

Specificity And Sensitivity ◽

Potential Applications ◽

Good Substitute

Mannosylated lipoarabinomannan (ManLAM), a complex lipoglycan, is a major component of Mycobacterium tuberculosis, the agent of tuberculosis (TB), and is an antigen used for serological diagnosis of TB. Screening random phage-display peptide libraries with anti-ManLAM mAb CS40 for peptide epitope mimics (mimotopes) led to the isolation of a panel of peptides. One of these peptides (B11) was characterized as a ManLAM mimotope: it bound the anti-ManLAM CS40 mAb and competed with ManLAM for antibody binding. Mice immunized with keyhole limpet haemocyanin-conjugated B11 peptide in a proper adjuvant developed antibodies that recognized ManLAM. Competition experiments demonstrated that the B11 peptide inhibited binding of mAb CS40 to ManLAM in a concentration-dependent manner. The data indicated that the affinity of CS40 mAb to B11 (K D 1.33×10−8) is higher than its affinity to ManLAM (K D 3.00×10−7). The sera of TB patients, as well as the sera of mice experimentally infected with M. tuberculosis, contained significant levels of antibodies that recognized both the B11 peptide and ManLAM. The specificity and sensitivity of the ELISA B11-based test were similar to those of the ELISA ManLAM-based test, indicating that the B11 antigen could be a good substitute for ManLAM serology for the diagnosis of TB.

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A Near-infrared Turn-on Fluorescent Sensor for Sensitive and Specific Detection of Albumin from Urine Samples

Sensors ◽

10.3390/s20041232 ◽

2020 ◽

Vol 20 (4) ◽

pp. 1232 ◽

Cited By ~ 1

Author(s):

Yoonjeong Kim ◽

Eunryeol Shin ◽

Woong Jung ◽

Mi Kyoung Kim ◽

Youhoon Chong

Keyword(s):

Binding Site ◽

Near Infrared ◽

Limit Of Detection ◽

Fluorescent Sensor ◽

Cost Effective ◽

Urine Samples ◽

Quantitative Detection ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Turn On

A readily synthesizable fluorescent probe DMAT-π-CAP was evaluated for sensitive and selective detection of human serum albumin (HSA). DMAT-π-CAP showed selective turn-on fluorescence at 730 nm in the presence of HSA with more than 720-fold enhancement in emission intensity ([DMAT-π-CAP] = 10 μM), and rapid detection of HSA was accomplished in 3 s. The fluorescence intensity of DMAT-π-CAP was shown to increase in HSA concentration-dependent manner (Kd = 15.4 ± 3.3 μM), and the limit of detection of DMAT-π-CAP was determined to be 10.9 nM (0.72 mg/L). The 1:1 stoichiometry between DMAT-π-CAP and HSA was determined, and the displacement assay revealed that DMAT-π-CAP competes with hemin for the unique binding site, which rarely accommodates drugs and endogenous compounds. Based on the HSA-selective turn-on NIR fluorescence property as well as the unique binding site, DMAT-π-CAP was anticipated to serve as a fluorescence sensor for quantitative detection of the HSA level in biological samples with minimized background interference. Thus, urine samples were directly analyzed by DMAT-π-CAP to assess albumin levels, and the results were comparable to those obtained from immunoassay. The similar sensitivity and specificity to the immunoassay along with the simple, cost-effective, and fast detection of HSA warrants practical application of the NIR fluorescent albumin sensor, DMAT-π-CAP, in the analysis of albumin levels in various biological environments.

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