Designing a label-free electrochemical aptasensor based on polypyrrole-l-cysteine-reduced graphene oxide nanocomposite for detection of 25-hydroxyvitamin D3.

Reliable and precise quantification of 25-hydroxyvitamin D3 in clinical samples is vital because vitamin D3 deficiency lead to several disorders, such as mental illness, osteoporosis, and coronavirus disease. Herein, we report the fabrication of a novel electrochemical aptasensor using a nanocomposite, including reduced graphene oxide, pyrrole, and l-cysteine, for the sensitive detection of 25-hydroxyvitamin D3 . Subsequently, the aptamer of 25-hydroxyvitamin D3 was immobilized on the surface of the modified electrode. Differential pulse voltammetry signals were utilized for studying the binding and measurement of 25-hydroxyvitamin D3 based on the oxidation peak. Under the optimum conditions, the designed electrochemical aptasensor exhibited a linear detection range of 0.001-150 nM, with a limit of detection of 0.006 nM. Furthermore, the proposed aptasensor selectively detected 25-hydroxyvitamin D3 compared to other analogs. Moreover, this aptasensor was successfully applied for the detection of 25-hydroxyvitamin D3 in human serum samples, which were quantified by the enzyme-linked immunosorbent assay method. The acceptable recoveries of 82.67%-111.07% demonstrated that this proposed electrochemical aptasensor can be a promising alternative for clinical methods of vitamin D determination.

A new molecularly imprinted polymer electrochemical sensor based on CuCo2 O4 /N-doped CNTs/P-doped GO nanocomposite for detection of 25-hydroxyvitamin D3 in serum samples.

25-Hydroxyvitamin D3 as a main circulating metabolite of vitamin D is usually measured in serum to evaluate the vitamin D status of humans. So, developing an accessible, fast response, sensitive, and selective detection method for 25-hydroxyvitamin D3 is highly important. In this study, we designed a sensitive and selective electrochemical sensor based on the modification of glassy carbon electrode by nanocomposite of CuCo2 O4 /nitrogen-doped carbon nanotubes and phosphorus-doped graphene oxide. Then 25-hydroxyvitamin D3 -imprinted polypyrrole was coated on the electrode surface through electropolymerization. Moreover, ferricyanide was used as a mediator for the creation of a readable signal, which was considerably decreased after rebinding of 25-hydroxyvitamin D3 on the electrode. The proposed sensor successfully detected 25-hydroxyvitamin D3 in the range of 0.002-10 µM, with a detection limit of 0.38 nM, which was highly lower than deficiency concentration (20 ng/ml; 49.92 nM). Finally, the proposed sensor was checked for detection of 25-hydroxyvitamin D3 in serum samples with recovery in the range of 80%-106.42%. The results demonstrated the applicability of the designed sensor for the detection of 25-hydroxyvitamin D3 in biological samples.

Diagnostic genosensor for detection of rotavirus based on HFGNs/MXene/PPY signal amplification.

A novel genosensor was developed for rotavirus specific cDNA sequence detection. The genosensor was comprised of hierarchical flower-like gold nanostructures, MXene, and polypyrrole (HFGNs/MXene/PPY) nanocomposite as a signal amplification tag, specific antisense ssDNA oligonucleotide as a recognition bioelement, and methylene blue (MB) as a redox marker. The morphological and electrochemical features of the biosensor were first tested and optimized and the high performance of the platform was confirmed in terms of sensitivity and reproducibility. Then, 20 rotavirus RNA isolated from clinical and cell-cultured samples (10 positive and 10 negative confirmed by RT-PCR and electrophoresis methods) were evaluated by the genosensor. The analysis results revealed that the genosensor is able to differentiate successfully between the positive and negative control groups. The developed genosensor for rotavirus RNA detection presented an excellent limit of detection of ∼ 0.8 aM and a determination  range of  10-18 and 10-7 M. In addition, the ssDNA/HFGNs/MXene/PPY/GCE showed high selectivity and long-term stability of ~ 24 days. Therefore, this novel genosensor would be of great benefit for the clinical diagnosis of rotavirus.

A label-free electrochemical biosensor based on PBA-Au-MXene QD for miR-122 detection in serum samples.

A poly(n-butyl acrylate)-gold-MXene quantum dots (PBA-Au-MXene QD) nanocomposite-based biosensor is presented that is modified by unique antisense single-stranded DNA (ssDNA) and uses the electrochemical detection methods of DPV, CV, and EIS to early detect miR-122 as a breast cancer biomarker in real clinical samples. This fabrication method is based on advanced nanotechnology, at which a poly(n-butyl acrylate) (PBA) as a non-conductive polymer transforms into a conductive composite by incorporating Au-MXene QD. This biosensor had a limit of detection (LOD) of 0.8 zM and a linear range from 0.001 aM to 1000 nM, making it capable of detecting the low concentrations of miR-122 in patient samples. Moreover, it allows approximately 100% sensitivity and 100% specificity for miR-122 without extraction. The synthesis and detection characteristics were evaluated by different complementary tests such as AFM, FTIR, TEM, and FESEM. This new biosensor can have a high potential in clinical applications to detect breast cancer early and hence improve patient outcomes.

Development of detection methods for the diagnosis and analysis of highly toxic metal phosphides: A comprehensive and critical review.

Metal phosphides, especially aluminum phosphide, and phosphine (PH3 ) are widely used as insecticides and rodenticides for protection of grains during process of storage and transportation. The main reason of poisoning with this compound is related to the conscious ingestion of salts or accidental inhalation of PH3 . So the early and accurate diagnosis of poisoning can significantly help to the effective clinical treatment or recognition of death cause. PH3 is somewhat unstable due to reaction with oxygen or hemoglobin leading to formation of oxy-acids phosphorous. Here, we critically reviewed the literature introducing the quantitative and qualitative methods for the detection of metal phosphides, PH3 , and its products. This study obviously demonstrates that during past years, different diagnosis methods have been remarkably progressed. Head-space gas chromatography and confirmatory colorimetric methods have been as the most popular techniques. Also, the gas sensors are a promising method that must be more progressed.

The overview and perspectives of biosensors and Mycobacterium tuberculosis: A systematic review.

Tuberculosis (TB) is referred to as a "consumption" or phthisis, which has been a fatal human disease for thousands of years. Mycobacterium tuberculosis (M. tb) might have been responsible for the death of more humans than any other bacterial pathogens. Therefore, the rapid diagnosis of this bacterial infection plays a pivotal role in the timely and appropriate treatment of the patients, as well as the prevention of disease spread. More than 98% of TB cases are reported in developing countries, and due to the lack of well-equipped and specialized diagnostic laboratories, development of effective diagnostic methods based on biosensors is essential for this bacterium. In this review, original articles published in English were retrieved from multiple databases, such as PubMed, Scopus, Google Scholar, Science Direct, and Cochrane Library during January 2010-October 2019. In addition, the reference lists of the articles were also searched. Among 109 electronically searched citations, 42 articles met the inclusion criteria. The highest potential and wide usage of biosensors for the diagnosis of M. tb and its drug resistance belonged to DNA electrochemical biosensors (isoniazid and rifampin strains). Use of biosensors is expanding for the detection of resistant strains of anti-TB antibiotics with high sensitivity and accuracy, while the speed of these sensory methods is considered essential as well. Furthermore, the lowest limit of detection (0.9 fg/ml) from an electrochemical DNA biosensor was based on graphene-modified iron-oxide chitosan hybrid deposited on fluorine tin oxide for the MPT64 antigen target. According to the results, the most common methods used for M. tb detection include acid-fast staining, cultivation, and polymerase chain reaction (PCR). Although molecular techniques (e.g., PCR and real-time PCR) are rapid and sensitive, they require sophisticated laboratory and apparatuses, as well as skilled personnel and expertise in the commentary of the results. Biosensors are fast, valid, and cost-efficient diagnostic method, and the improvement of their quality is of paramount importance in resource-constrained settings.

A review of biosensors for the detection of B-type natriuretic peptide as an important cardiovascular biomarker.

Heart disease, as the most serious threat to human health globally, is responsible for rising mortality rates, largely due to lifestyle and diet. Unfortunately, the main problem for patients at high risk of heart disease is the validation of prognostic tests. To this end, the detection of cardiovascular biomarkers has been employed to obtain pathological and physiological information in order to improve prognosis and early-stage diagnosis of chronic heart failure. Short-term changes in B-type natriuretic peptide are known as a standard and important biomarker for diagnosis of heart failure. The most important problem for detection is low concentration and short half-life in the blood. The normal concentration of BNP in blood is less than 7 nM (25 pg/mL), which increases significantly to more than 80 pg/mL. Therefore, the development of new biosensors with better sensitivity, detection limit, and dynamic range than current commercial kits is urgently needed. This review classifies the biosensors designed for detection of BNP into electrochemical, optical, microfluidic, and lateral-flow immunoassay techniques. The review clearly demonstrates that a variety of immunoassay, aptasensor, enzymatic and catalytic nanomaterials, and fluorophores have been successfully employed for detection of BNP at low attomolar ranges. Dtection of B-type natriuretic peptide with biosensors.

Rapid and label-free electrochemical DNA biosensor based on a facile one-step electrochemical synthesis of rGO-PPy-(L-Cys)-AuNPs nanocomposite for the HTLV-1 oligonucleotide detection.

Human T cell leukemia virus type 1 (HTLV-1) as the first human retrovirus is currently a serious endemic health challenge. Despite the use of assorted molecular or serological assays for HTLV-1 detection, there are several limitations due to the lack of a confirmatory test that may affect the accuracy of the results. Herein, a novel label-free biosensor for the detection of HTLV-1 Tax gene has been reported. An electrochemical facile ecofriendly synthesis method has been demonstrated based on a synthesis of nanocomposite of reduced graphene oxide, polypyrrole, and gold nanoparticles (rGO-PPy-(l-Cys)-AuNPs) deposited on the surface of screen-printed carbon electrode. Electrochemical techniques were used to characterize and study the electrochemical behavior of the rGO-PPy-(l-Cys)-AuNPs, which exhibited a stable reference peak at 0.21 V associated with hybridization forms by applying the differential pulse voltammetry. The designed DNA biosensor presented a wide linear range from 0.1 fM to 100 µM and a low detection limit of 20 atto-molar. The proposed biosensor presented in this study provides outstanding selectivity, sensitivity, repeatability, and reproducibility.

Nanotechnology-driven advances in the treatment of diabetic wounds.

Diabetic foot ulcers (DFUs) are chronic severe complications of diabetes disease and remain a worldwide clinical challenge with social and economic consequences. Diabetic wounds can cause infection, amputation of lower extremities, and even death. Several factors including impaired angiogenesis, vascular insufficiency, and bacterial infections result in a delayed process of wound healing in diabetic patients. Treatment of wound infections using traditional antibiotics has become a critical status. Thus, finding new therapeutic strategies to manage diabetic wounds is urgently needed. Nanotechnology has emerged as an efficient approach for this purpose. This review aimed to summarize recent advances using nanotechnology for the treatment of diabetic wounds.

An overview and bibliometric analysis on the colorectal cancer therapy by magnetic functionalized nanoparticles for the responsive and targeted drug delivery.

With the growing demands for personalized medicine and medical devices, nanomedicine is a modern scientific field, and research continues to apply nanomaterials for therapeutic and damaged tissue diagnosis. In this regard, substantial progress has been made in synthesizing magnetic nanoparticles with desired sizes, chemical composition, morphologies, and surface chemistry. Among these materials, nanomagnetic iron oxides have demonstrated promise as unique drug delivery carriers due to cancer treatment. This carrier could lead to responsive properties to a specific trigger, including heat, pH, alternative magnetic field, or even enzymes, through functionalization and coating of magnetic nanoparticles, along with biocompatibility, good chemical stability, easy functionalization, simple processing, and ability to localize to the tumor site with the assistance of external magnetic field. Current studies have focused on magnetic nanoparticles' utilities in cancer therapy, especially for colorectal cancer. Additionally, a bibliometric investigation was performed on the public trends in the field of the magnetic nanoparticle to drug delivery and anticancer, which represented progressing applications of these carriers in the multidisciplinary zones with a general view on future research and identified potential opportunities and challenges. Furthermore, we outline the current challenges and forthcoming research perspective for high performance and fostering advanced MNPs in colorectal cancer treatment.

Association of vitamin D status with liver and kidney disease: A systematic review of clinical trials, and cross-sectional and cohort studies.

Background: Vitamin D deficiency (VDD) is a major public health problem. There are few comprehensive systematic reviews about the relationship between Vitamin D status and liver and renal disease in Iran. Methods: We systemically searched the following databases: Web of Science; PubMed; Cochrane Library; Scopus; Science Direct; Google Scholar and two Iranian databases (Scientific Information Database (SID) and IranMedex) up until November 2017 to identify all randomized control trials (RCTs), case control, cross-sectional and cohort studies investigating the association between vitamin D and any form of liver or kidney disease. Results: Vitamin D insufficiency, or deficiency (VDD), is highly prevalent in Iran, reports varying between 44.4% in Isfahan to 98% in Gorgan. There is also a high prevalence of VDD among patients with liver or kidney disease, and the administration of vitamin D supplements may have beneficial effects on lipid profile, blood glucose, liver function and fatty liver disease, and bone health. Low serum vitamin D levels are related with abnormalities in these laboratory and clinical parameters. Conclusion: VDD is prevalent in patients with chronic liver or renal disease in Iran. There appear to be several beneficial effects of vitamin D supplementation in vitamin D deficient patients with liver or kidney disease.

Aptamers as potential recognition elements for detection of vitamins and minerals: a systematic and critical review.

Background: Vitamin and mineral deficiencies are prevalent globally, and extensive efforts have been made to assess their status. Most traditional methods are expensive and time-consuming; therefore, developments of rapid, simple, specific, and sensitive methods for the assessment of vitamins and minerals in biological samples are of high importance in research. Aptamers are synthetic nucleic acid single-stranded DNA or RNA that can be synthesized in vitro. They can be engineered to be analyte-specific and have been suggested as a substitute for monoclonal antibodies, due to their high sensitivity and affinity. In addition, aptamers can be chemically synthesized and readily modified for use as biosensors. These features make aptamers a promising tool for the detection of biological analytes. In this review, we provide an overview of the potential use of aptamer-based biosensors.Methods: Search terms were conducted on several online databases, including Google Scholar, PubMed, Scopus, and Science Direct from January 2000 to August 2019. Eligibility criteria were used and quality evaluation was performed. Following the review of 4349 articles, 39 articles met the inclusion criteria.Results: Aptasensors have recently been developed for the detection of vitamins by using optical methods, with a detection range from 74 pM to 204 pM, and lower limit of detection of 2.4 pM. Both electrochemical and optical methods have been used for detection of minerals, however electrochemical methods show a wider linear range and lower detection limits compared to optical methods with a wide linear range from 0.2 fM to 1.0 mM and limit of detection of 14.7 fM.Conclusion: The current report reviews recent developments in aptamer-based biosensors for detection of vitamins and minerals. Studies have shown that aptasensors' properties are suitable for the quantification of vitamins and minerals with high sensitivity, affinity, and specificity. Nevertheless, the limitations and future directions of aptamers require further research and new technological innovation.

Exosomes: New insights into cancer mechanisms.

Exosomes are mobile extracellular vesicles with a diameter 40 to 150 nm. They play a critical role in several processes such as the development of cancers, intercellular signaling, drug resistance mechanisms, and cell-to-cell communication by fusion onto the cell membrane of recipient cells. These vesicles contain endogenous proteins and both noncoding and coding RNAs (microRNA and messenger RNAs) that can be delivered to various types of cells. Furthermore, exosomes exist in body fluids such as plasma, cerebrospinal fluid, and urine. Therefore, they could be used as a novel carrier to deliver therapeutic nucleic-acid drugs for cancer therapy. It was recently documented that, hypoxia promotes exosomes secretion in different tumor types leading to the activation of vascular cells and angiogenesis. Cancer cell-derived exosomes (CCEs) have been used as prognostic and diagnostic markers in many types of cancers because exosomes are stable at 4°C and -70°C. CCEs have many functional roles in tumorigenesis, metastasis, and invasion. Consequently, this review presents the data about the therapeutic application of exosomes and the role of CCEs in cancer invasion, drug resistance, and metastasis.

Early-stage cervical cancer diagnosis based on an ultra-sensitive electrochemical DNA nanobiosensor for HPV-18 detection in real samples.

BACKGROUND: In several years ago, infection with human papillomaviruses (HPVs), have been prevalent in the worlds especially HPV type 18, can lead to cervical cancer. Therefore, rapid, accurate, and early diagnosis of HPV for successful treatment is essential. The present study describes the development of a selective and sensitive electrochemical biosensor base on DNA, for early detection of HPV-18. For this purpose, a nanocomposite of reduced graphene oxide (rGO) and multiwalled carbon nanotubes (MWCNTs) were electrodeposited on a screen-printed carbon electrode (SPCE). Then, Au nanoparticles (AuNPs) were dropped on a modified SPCE. Subsequently, single strand DNA (ssDNA) probe was immobilized on the modified electrode. The link attached between AuNPs and probe ssDNA provided by L-cysteine via functionalizing AuNPs (Cys-AuNPs). The differential pulse voltammetry (DPV) assay was also used to electrochemical measurement. The measurement was based on the oxidation signals of anthraquninone-2-sulfonic acid monohydrate sodium salt (AQMS) before and after hybridization between the probe and target DNA. RESULTS: The calibration curve showed a linear range between 0.01 fM to 0.01 nM with a limit of detection 0.05 fM. The results showed that the optimum concentration for DNA probe was 5 µM. The good performance of the proposed biosensor was achieved through hybridization of DNA probe-modified SPCE with extracted DNA from clinical samples. CONCLUSIONS: According to the investigated results, this biosensor can be introduced as a proprietary, accurate, sensitive, and rapid diagnostic method of HPV 18 in the polymerase chain reaction (PCR) of real samples.

Scavenger receptor Class B type I as a potential risk stratification biomarker and therapeutic target in cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of mortality globally. There are few useful markers available for CVD risk stratification that has proven clinical utility. Scavenger receptor B type I (SR-BI) is a cell surface protein that plays a major role in cholesterol homeostasis through its interaction with high-density lipoprotein-cholesterol (HDL-C) esters (CE). HDL delivers CE to the liver through selective uptake by the SR-BI. SR-BI also regulates the inflammatory response. It has been shown that SR-BI overexpression has beneficial, protective effects in atherogenesis, and there is considerable interest in developing antiatherogenic strategies that involve SR-BI-mediated increases in reverse cholesterol transport through HDL and/or low-density lipoprotein. Further investigations are essential to explore the clinical utility of this approach. Moreover, there is growing evidence showing associations between genetic variants with modulation of SR-BI function that may, thereby, increase CVD risk. The aim of the current review was to provide an overview of the possible molecular mechanisms by which SR-BI may affect CVD risk, and the clinical implications of this, with particular emphasis on preclinical studies on genetic changes of SR-BI and CVD risk.

The clinical impact of exosomes in cardiovascular disorders: From basic science to clinical application.

Cardiovascular disease (CVD) is the major cause of death globally; therefore, there is a need for the identification of a valid biomarker that accurately predicts the risk of developing CVD, and novel therapeutic approaches for its treatment. Exosomes are very small extracellular vesicles containing protein, lipid, transcription factors, messenger RNAs, noncoding RNA, and nucleic acid contents that are important players in intercellular communication, and that act via long-range signals or cell-to-cell contact. The discovery of exosomes provides potential strategies for the diagnosis and treatment of CVD. In the current review, we have explored the potential impact of exosomes on cardiovascular physiology, and their therapeutic potential in cardiovascular disorders with an emphasis on the existing preclinical studies.

Reactive oxygen species in colorectal cancer: The therapeutic impact and its potential roles in tumor progression via perturbation of cellular and physiological dysregulated pathways.

Reactive oxygen species (ROS) are produced by mitochondria during metabolism. In physiological states, the production of ROS and their elimination by antioxidants are kept in balance. However, in pathological states, elevated levels of ROS interact with susceptible cellular target compounds including lipids, proteins, and DNA and deregulate oncogenic signaling pathways that are involved in colorectal cancer (CRC) carcinogenesis. Although antioxidant compounds have been successfully used in the treatment of CRC as prevention approaches, they have also been shown in some cases to promote disease progression. In this review, we focus on the role of ROS in gastrointestinal homeostasis, CRC progression, diagnosis, and therapy with particular emphasis on ROS-stimulated pathways.

Current approaches for detection of human T-lymphotropic virus Type 1: A systematic review.

BACKGROUND: Human T-lymphotropic virus Type 1 (HTLV-1) is a retrovirus that is endemic in some regions of the world. It is known to cause several diseases like adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Serology and molecular methods have been used to detect this virus. Of these, enzyme-linked immunosorbent assay (ELISA) is used as a primary screening method and this is usually followed by western blotting (WB) and polymerase chain reaction (PCR) methods as confirmatory tests. We conducted a systematic review of the different techniques used in the diagnosis of HTLV-1 infection. MATERIALS AND METHODS: Our search was limited to original papers in the English language from 2010 to 2018 using several databases including Pubmed, Scopus, Google Scholar, Iranmedex, and Scientific Information Database. A manual search of references provided in the included papers was also performed. RESULTS: Of 101 electronically searched citations, 43 met the inclusion criteria. ELISA is commonly used for qualitative and screening detection, and WB and PCR techniques are used to confirm infection. CONCLUSION: Among all the reported methods for detection of HTLV-1, only serological and molecular tests are used as the most common technical assays for HTLV-1. The ELISA assay, without a confirmatory test, has several limitations and affect the accuracy of the results. Owing to the prevalence of HTLV-1 and limitations of the current detection methods, further evaluation of the accuracy of these methods is needed. There are new opportunities for applying novel technological advances in microfluidics, biosensors, and lab-on-a-chip systems to perform HTLV-1 diagnostics.

The potential prognostic and therapeutic application of tissue and circulating microRNAs in cervical cancer.

Cervical cancer (CC) is a common malignancy in women and a major cause of cancer-related mortality globally. Some novel biomarkers may enable the early diagnosis and monitoring of CC. MicroRNAs (miRNAs) are small noncoding RNAs that control gene translation at a posttranscriptional level. Hence the deregulation of these molecules can cause many diseases. There appears to be an association between aberrant miRNA expression and CC, but the molecular mechanisms involved in the development of CC remain unknown. The upregulation of some circulating miRNAs, for example, miRNA-20a, miRNA-203, miRNA-21, miRNA-205, miRNA-218, and miR-485-5, as well as tissue-specific miRNAs, for example, miR-7, miR-10a, miR-17-5p, miR-135b, miR-149, and miR-203 have been found in patients with CC. There is also growing evidence for the importance of miRNAs in the development of drug resistance. This review therefore highlights recently published preclinical and clinical investigation performed on tissue specific and circulating miRNAs, as potential biomarkers for the detection of patients at early stages of CC, in the prediction of prognosis, and monitoring of their response to therapy.

A genetic variant in CDKN2A/2B locus was associated with poor prognosis in patients with esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer related death. Despite of extensive efforts in identifying valid cancer prognostic biomarkers, only a very small number of markers have been identified. Several genetic variants in the 9p21 region have been identified that are associated with the risk of multiple cancers. Here, we explored the association of two genetic variants in the 9p21 region, CDKN2A/B, rs10811661, and rs1333049 for the first time in 273 subjects with, or without ESCC. We observed that the patients with ESCC had a higher frequency of a TT genotype for rs10811661 than individuals in the control group, and this polymorphism was also associated with tumor size. Moreover, a CC genotype for the rs1333049 polymorphism was associated with a reduced overall survival (OS) of patients with ESCC. In particular, patients with a CC (rs1333049) genotype had a significantly shorter OS (CC genotype: 34.5 ± 8.9 months vs. CG+GG: 47.7 ± 5.9 months; p value = 0.03). We have also shown the association of a novel genetic variant in CDKN2B gene with clinical outcome of patients with ESCC. Further investigations are warranted in a larger population to explore the value of emerging markers as a risk stratification marker in ESCC.