scholarly journals The Uprising of Mitochondrial DNA Biomarker in Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Siti Zulaikha Nashwa Mohd Khair ◽  
Siti Muslihah Abd Radzak ◽  
Abdul Aziz Mohamed Yusoff
Keyword(s):  
Mitochondrial Dna ◽  
Cross Talk ◽  
Nuclear Genome ◽  
Cancer Therapeutics ◽  
High Specificity ◽  
Research Field ◽  
Epigenetic Alterations ◽  
Clinical Practices ◽  
Therapeutic Approaches ◽  
Specificity And Sensitivity

Cancer is a heterogeneous group of diseases, the progression of which demands an accumulation of genetic mutations and epigenetic alterations of the human nuclear genome or possibly in the mitochondrial genome as well. Despite modern diagnostic and therapeutic approaches to battle cancer, there are still serious concerns about the increase in death from cancer globally. Recently, a growing number of researchers have extensively focused on the burgeoning area of biomarkers development research, especially in noninvasive early cancer detection. Intergenomic cross talk has triggered researchers to expand their studies from nuclear genome-based cancer researches, shifting into the mitochondria-mediated associations with carcinogenesis. Thus, it leads to the discoveries of established and potential mitochondrial biomarkers with high specificity and sensitivity. The research field of mitochondrial DNA (mtDNA) biomarkers has the great potential to confer vast benefits for cancer therapeutics and patients in the future. This review seeks to summarize the comprehensive insights of nuclear genome cancer biomarkers and their usage in clinical practices, the intergenomic cross talk researches that linked mitochondrial dysfunction to carcinogenesis, and the current progress of mitochondrial cancer biomarker studies and development.

scholarly journals miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 276 ◽  
Author(s):  
Carmen Elena Condrat ◽  
Dana Claudia Thompson ◽  
Madalina Gabriela Barbu ◽  
Oana Larisa Bugnar ◽  
Andreea Boboc ◽  
...  
Keyword(s):  
High Specificity ◽  
Research Field ◽  
Therapeutic Interventions ◽  
Protein Levels ◽  
Diagnosis And Prognosis ◽  
Specificity And Sensitivity ◽  
Online Databases ◽  
Patient Profiles ◽  
Potential Use ◽  
Made In

MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.

Prospective Application of Aptamer-based Assays and Therapeutics in Bloodstream Infections

2020 ◽  
Vol 20 (10) ◽  
pp. 831-840
Author(s):  
Weibin Li
Keyword(s):  
Pathogenic Bacteria ◽  
Genetic Diagnosis ◽  
Bloodstream Infections ◽  
High Specificity ◽  
Peptide Sequence ◽  
High Morbidity ◽  
Specificity And Sensitivity ◽  
Prospective Application ◽  
Small Molecule Therapeutics

Sepsis is still a severe health problem worldwide with high morbidity and mortality. Blood bacterial culture remains the gold standard for the detection of pathogenic bacteria in bloodstream infections, but it is time-consuming, and both the sophisticated equipment and well-trained personnel are required. Immunoassays and genetic diagnosis are expensive and limited to specificity and sensitivity. Aptamers are single-stranded deoxyribonucleic acid (ssDNA) and ribonucleic acid (RNA) oligonucleotide or peptide sequence generated in vitro based on the binding affinity of aptamer-target by a process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). By taking several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch-to-batch variation, flexible modification and production, thermal stability, low immunogenicity and lack of toxicity, aptamers are presently becoming promising novel diagnostic and therapeutic agents. This review describes the prospective application of aptamerbased laboratory diagnostic assays and therapeutics for pathogenic bacteria and toxins in bloodstream infections.

Development of a mito-CRISPR system for generating mitochondrial DNA-deleted strain in Saccharomyces cerevisiae

2020 ◽  
Vol 85 (4) ◽  
pp. 895-901
Author(s):  
Takamitsu Amai ◽  
Tomoka Tsuji ◽  
Mitsuyoshi Ueda ◽  
Kouichi Kuroda
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mitochondrial Dna ◽  
Ethidium Bromide ◽  
Nuclear Genome ◽  
Target Sequence ◽  
Guide Rna ◽  
Crispr System ◽  
Mitochondrial Target ◽  
Gene Treatment ◽  
Mtdna Deletion

ABSTRACT Mitochondrial dysfunction can occur in a variety of ways, most often due to the deletion or mutation of mitochondrial DNA (mtDNA). The easy generation of yeasts with mtDNA deletion is attractive for analyzing the functions of the mtDNA gene. Treatment of yeasts with ethidium bromide is a well-known method for generating ρ° cells with complete deletion of mtDNA from Saccharomyces cerevisiae. However, the mutagenic effects of ethidium bromide on the nuclear genome cannot be excluded. In this study, we developed a “mito-CRISPR system” that specifically generates ρ° cells of yeasts. This system enabled the specific cleavage of mtDNA by introducing Cas9 fused with the mitochondrial target sequence at the N-terminus and guide RNA into mitochondria, resulting in the specific generation of ρ° cells in yeasts. The mito-CRISPR system provides a concise technology for deleting mtDNA in yeasts.

scholarly journals LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 195
Author(s):  
Francisca Dias ◽  
Cristina Almeida ◽  
Ana Luísa Teixeira ◽  
Mariana Morais ◽  
Rui Medeiros
Keyword(s):  
Colorectal Cancer ◽  
Amino Acid ◽  
Cancer Progression ◽  
Cell Metabolism ◽  
Tumor Development ◽  
Amino Acid Transporters ◽  
Epigenetic Alterations ◽  
Therapeutic Approaches ◽  
Colorectal Cancer Progression ◽  
Made In

The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results. In this review we combine a bioinformatic approach with a literature review in order to identify a miRNA profile with the potential to target both LAT1 and ASCT2 with potential to be used as a therapeutic approach against CRC.

scholarly journals SARS-CoV-2 specific antibody and neutralization assays reveal the wide range of the humoral immune response to virus

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mikail Dogan ◽  
Lina Kozhaya ◽  
Lindsey Placek ◽  
Courtney Gunter ◽  
Mesut Yigit ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
High Specificity ◽  
Spike Protein ◽  
Humoral Immune ◽  
Specificity And Sensitivity ◽  
Wide Range ◽  
Specific Igg ◽  
Negative Controls

AbstractDevelopment of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n = 115) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. SARS-CoV-2 neutralization was determined in COVID-19 and convalescent plasma at up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which were also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Interestingly, some COVID-19 patients also possessed NAbs against SARS-CoV Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines.

scholarly journals Highly Sensitive Fluorescent Detection of Acetylcholine Based on the Enhanced Peroxidase-Like Activity of Histidine Coated Magnetic Nanoparticles

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1207
Author(s):  
Hong Jae Cheon ◽  
Quynh Huong Nguyen ◽  
Moon Il Kim
Keyword(s):  
Magnetic Nanoparticles ◽  
High Sensitivity ◽  
High Specificity ◽  
Choline Oxidase ◽  
Fluorescent Detection ◽  
One Pot ◽  
Site Structure ◽  
Specificity And Sensitivity ◽  
Highly Sensitive ◽  
Peroxidase Mimics

Inspired by the active site structure of natural horseradish peroxidase having iron as a pivotal element with coordinated histidine residues, we have developed histidine coated magnetic nanoparticles (His@MNPs) with relatively uniform and small sizes (less than 10 nm) through one-pot heat treatment. In comparison to pristine MNPs and other amino acid coated MNPs, His@MNPs exhibited a considerably enhanced peroxidase-imitating activity, approaching 10-fold higher in catalytic reactions. With the high activity, His@MNPs then were exploited to detect the important neurotransmitter acetylcholine. By coupling choline oxidase and acetylcholine esterase with His@MNPs as peroxidase mimics, target choline and acetylcholine were successfully detected via fluorescent mode with high specificity and sensitivity with the limits of detection down to 200 and 100 nM, respectively. The diagnostic capability of the method is demonstrated by analyzing acetylcholine in human blood serum. This study thus demonstrates the potential of utilizing His@MNPs as peroxidase-mimicking nanozymes for detecting important biological and clinical targets with high sensitivity and reliability.

scholarly journals HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3575
Author(s):  
Dimitris Karagiannis ◽  
Theodoros Rampias
Keyword(s):  
Tumor Heterogeneity ◽  
Histone Deacetylase Inhibitors ◽  
Phenotypic Variability ◽  
Hdac Inhibitors ◽  
Cancer Therapeutics ◽  
Mechanisms Of Action ◽  
Therapeutic Approaches ◽  
Cellular Processes ◽  
Environmental Selection ◽  
Stochastic Events

Intra-tumoral heterogeneity presents a major obstacle to cancer therapeutics, including conventional chemotherapy, immunotherapy, and targeted therapies. Stochastic events such as mutations, chromosomal aberrations, and epigenetic dysregulation, as well as micro-environmental selection pressures related to nutrient and oxygen availability, immune infiltration, and immunoediting processes can drive immense phenotypic variability in tumor cells. Here, we discuss how histone deacetylase inhibitors, a prominent class of epigenetic drugs, can be leveraged to counter tumor heterogeneity. We examine their effects on cellular processes that contribute to heterogeneity and provide insights on their mechanisms of action that could assist in the development of future therapeutic approaches.

scholarly journals Mitochondrial DNA Methylation and Human Diseases

2021 ◽  
Vol 22 (9) ◽  
pp. 4594
Author(s):  
Andrea Stoccoro ◽  
Fabio Coppedè
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Nuclear Genome ◽  
Epigenetic Modifications ◽  
Human Diseases ◽  
Loop Region ◽  
D Loop

Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

scholarly journals Serum MicroRNA Signature as a Diagnostic and Therapeutic Marker in Patients with Psoriatic Arthritis

2020 ◽  
Vol 47 (12) ◽  
pp. 1760-1767
Author(s):  
Sarah M. Wade ◽  
Trudy McGarry ◽  
Siobhan C. Wade ◽  
Ursula Fearon ◽  
Douglas J. Veale
Keyword(s):  
Psoriatic Arthritis ◽  
Characteristic Curve ◽  
High Specificity ◽  
Serum Samples ◽  
Rna Molecules ◽  
Serum Mirna ◽  
Serum Microrna ◽  
Specificity And Sensitivity ◽  
European League Against Rheumatism ◽  
Noninvasive Markers

ObjectiveMicroRNA (miRNA) are small endogenous regulatory RNA molecules that have emerged as potential therapeutic targets and biomarkers in autoimmunity. Here, we investigated serum miRNA levels in patients with psoriatic arthritis (PsA) and further assessed a serum miRNA signature in therapeutic responder versus nonresponder PsA patients.MethodsSerum samples were collected from healthy controls (HC; n = 20) and PsA patients (n = 31), and clinical demographics were obtained. To examine circulatory miRNA in serum from HC and PsA patients, a focused immunology miRNA panel was analyzed utilizing a miRNA Fireplex assay (FirePlex Bioworks Inc.). MiRNA expression was further assessed in responders versus nonresponders according to the European League Against Rheumatism response criteria.ResultsSix miRNA (miR-221-3p, miR-130a-3p, miR-146a-5p, miR-151-5p, miR-26a-5p, and miR-21-5p) were significantly higher in PsA compared to HC (all P < 0.05), with high specificity and sensitivity determined by receiver-operating characteristic curve analysis. Analysis of responder versus nonresponders demonstrated higher baseline levels of miR-221-3p, miR-130a-3p, miR-146a-5p, miR-151-5p, and miR-26a-5p were associated with therapeutic response.ConclusionThis study identified a 6-serum microRNA signature that could be attractive candidates as noninvasive markers for PsA and may help to elucidate the disease pathogenesis.

scholarly journals Validity of the International Prostate Symptoms Score in predicting urinary retention after joint replacement

2019 ◽  
Vol 27 (3) ◽  
pp. 230949901986867 ◽  
Author(s):  
Alasdair JA Santini ◽  
Chetan A Jakaraddi ◽  
Fotis Polydoros ◽  
Sree Metikala
Keyword(s):  
Urinary Tract ◽  
Urinary Retention ◽  
Preoperative Evaluation ◽  
Age Groups ◽  
High Specificity ◽  
Logistic Regression Models ◽  
Prosthetic Joints ◽  
Specificity And Sensitivity ◽  
Urinary Tract Symptoms ◽  
Risk Patients

Postoperative urinary retention necessitating catheterization after major lower limb arthroplasty surgery adds to the patients’ postoperative discomfort and increases the risk of urinary tract infection with potential risk of transient bacteraemia and seeding of infection to prosthetic joints. Preoperative evaluation of patients with lower urinary tract symptoms may help to identify at-risk patients and the International Prostate Symptoms Score (IPSS) has been used as a screening tool to quantify the severity of symptoms in males. A prospective cohort of 303 patients undergoing total hip or knee arthroplasty was evaluated using the IPSS. Patients were categorized into three symptom groups (mild, moderate and severe based on scores of 0–7, 8–18 and greater than 18, respectively) and four age groups (<50 years, 51–60 years, 61–70 years and greater than 70 years). Twenty-six patients (8.6%) developed urinary retention and were catheterized postoperatively; of these, 16 were male and 10 were female. Statistical analysis using logistic regression models showed significant association between severe IPSS scores (>18) and urinary retention requiring catheterization in both males and females with both high specificity and sensitivity in the test in predicting postoperative catheterization. Hence, this test is a valid preoperative screen in predicting postoperative catheterization.

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