Marker-Dependent Cleavage of RNA by Binary (split) DNAzyme (BiDz) and Binary DNA Machines (BiDM).

Oligonucleotide gene therapy (OGT) can be used to suppress specific RNA in cells and thus has been explored for gene therapy. Despite extensive effort, there is no clinically significant OGT for treating cancer. Low efficiency of OGT is one of the problems.

Enhancing Sensitivity in Nucleic Acid Detection via Collaborative Multiple Catalytic Cores in DNAzyme Nanomachines.

We introduce a multicore DNA nanomachine (MDNM), utilizing four binary DNAzymes for nucleic acid detection without the need for a preamplification step. This innovation remarkably yields a reduction in limit of detection (LOD), over 5-fold, as compared to single-core systems. This reduces the required test time thus highlighting the potential of MDNM in advancing nucleic acid detection.

Cleaving Folded RNA by Multifunctional DNAzyme Nanomachines.

Both tight and specific binding of folded biological mRNA is required for gene silencing by oligonucleotide gene therapy agents. However, this is fundamentally impossible using the conventional oligonucleotide probes according to the affinity/specificity dilemma. This study addresses this problem for cleaving folded RNA by using multicomponent agents (dubbed 'DNA nanomachine' or DNM).

Multivalent DNAzyme agents for cleaving folded RNA.

Multivalent recognition and binding of biological molecules is a natural phenomenon that increases the binding stability (avidity) without decreasing the recognition specificity. In this study, we took advantage of this phenomenon to increase the efficiency and maintain high specificity of RNA cleavage by DNAzymes (Dz). We designed a series of DNA constructs containing two Dz agents, named here bivalent Dz devices (BDD).

RNase H-dependent DNA thresholder modulated by cancer marker concentration.

Threshold antisense oligonucleotide constructs were designed to cleave mRNA within different biomarker concentrations. The mRNA cleavage is activated by 2.6, 7.

Towards the development of a DNA automaton: modular RNA-cleaving deoxyribozyme logic gates regulated by miRNAs.

Advancements in DNA computation have unlocked molecular-scale information processing possibilities, utilizing the intrinsic properties of DNA for complex logical operations with transformative applications in biomedicine. DNA computation shows promise in molecular diagnostics, enabling precise and sensitive detection of genetic mutations and disease biomarkers. Moreover, it holds potential for targeted gene regulation, facilitating personalized therapeutic interventions with enhanced efficacy and reduced side effects.

DNAzyme Nanomachine with Fluorogenic Substrate Delivery Function: Advancing Sensitivity in Nucleic Acid Detection.

We have developed a hook-equipped DNA nanomachine (HDNM) for the rapid detection of specific nucleic acid sequences without a preamplification step. HDNM efficiently unwinds RNA structures and improves the detection sensitivity. Compared to the hookless system, HDNM offers an 80-fold and 13-fold enhancement in DNA and RNA detection, respectively, reducing incubation time from 3 to 1 h.

Cleaving Folded RNA with DNAzyme Agents.

Cleavage of biological mRNA by DNAzymes (Dz) has been proposed as a variation of oligonucleotide gene therapy (OGT). The design of Dz-based OGT agents includes computational prediction of two RNA-binding arms with low affinity (melting temperatures (T ) close to the reaction temperature of 37 °C) to avoid product inhibition and maintain high specificity. However, RNA cleavage might be limited by the RNA binding step especially if the RNA is folded in secondary structures.

Effect of Ramadan fasting on chronic inflammation markers and gut bacterial endotoxins among Egyptian hemodialysis patients.

Background: Chronic kidney disease (CKD) is associated with a state of chronic inflammation. This study aimed to investigate effects of Ramadan fasting on the markers of chronic inflammation and gut bacterial endotoxin levels in maintenance hemodialysis.

Method: A prospective self-controlled observational study included 45 patients.

Thresholding DNA Nanomachine as a Highly Cooperative and Efficient Enzyme-Like System for Controlled RNA Cleavage.

Therapeutic nucleic acid agents (TNA) can be activated by a marker RNA sequence followed by initiation of targeted RNA cleavage. This property can be used in conditional cell suppression, e. g.

Toward a Home Test for COVID-19 Diagnosis: DNA Machine for Amplification-Free SARS-CoV-2 Detection in Clinical Samples.

Nucleic acid-based detection of RNA viruses requires an annealing procedure to obtain RNA/probe or RNA/primer complexes for unwinding stable structures of folded viral RNA. In this study, we designed a protein-enzyme-free nano-construction, named four-armed DNA machine (4DNM), that requires neither an amplification stage nor a high-temperature annealing step for SARS-CoV-2 detection. It uses a binary deoxyribozyme (BiDz) sensor incorporated in a DNA nanostructure equipped with a total of four RNA-binding arms.

Binary Antisense Oligonucleotide Agent for Cancer Marker-Dependent Degradation of Targeted RNA.

Antisense oligonucleotide technology is one of the most successful gene therapy (GT) approaches. However, low selectivity of antisense agents limits their application as anticancer drugs. To achieve activation of antisense agent selectively in cancer cells, herein, we propose the concept of binary antisense oligonucleotide (biASO) agent.

RNA-Cleaving DNA Thresholder Controlled by Concentrations of miRNA Cancer Marker.

Oligonucleotide gene therapy (OGT) agents suppress specific mRNAs in cells and thus reduce the expression of targeted genes. The ability to unambiguously distinguish cancer from healthy cells can solve the low selectivity problem of OGT agents. Cancer RNA markers are expressed in both healthy and cancer cells with a higher expression level in cancer cells.

Effect of Ramadan fasting on arterial stiffness parameters among Egyptian hypertensive patients with and without chronic kidney disease.

Arterial stiffness (AS) increases progressively in patients with chronic kidney disease (CKD). It is a strong predictor of cardiovascular and all-cause mortality. This study aims at evaluate of the effect of Ramadan fasting on AS parameters, augmentation index (AIx), and pulse wave velocity (PWV) in hypertensive patients with and without CKD.

Insulin Resistance and Hepatitis C Virus-Associated Subclinical Inflammation Are Hidden Causes of Pruritus in Egyptian Hemodialysis Patients: A Multicenter Prospective Observational Study.

Background: Pruritus is one of the most common and disturbing symptoms in hemodialysis (HD) patients. The pathogenesis of pruritus in HD patients is multifactorial; however, a little progress in understanding this pathogenesis has been achieved.

Objectives: To evaluate the frequency and risk factors of pruritus among HD patients in Dakahlia, Egypt.

Rifaximin in nonalcoholic fatty liver disease: hit multiple targets with a single shot.

Background/aims: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) may include increased insulin resistance, upregulation of proinflammatory cytokines, lipopolysaccharide, and BMI. Rifaximin is a minimally absorbable antibiotic that might act against a broad spectrum of gut bacteria. This study aimed to investigate the effects of rifaximin on NAFLD.

Homocysteine: a new diagnostic marker in spontaneous bacterial peritonitis.

Background And Aims: The diagnosis of spontaneous bacterial peritonitis (SBP) depends primarily on a polymorphonuclear leukocyte cell count more than 250/mm. This method is invasive, and not diagnostic in all variants of SBP; we aimed to assess serum homocysteine as a precise indicative marker for the diagnosis of all variants of SBP.

Patients And Methods: A total 323 consecutive ascitic patients were registered in this prospective work.

New predictive factors of poor response to therapy in autoimmune hepatitis: role of mean platelet volume.

Background And Objectives: The response to immunosuppressive therapy in autoimmune hepatitis (AIH) is a matter of debate. The aim of this work is to identify the histological, biochemical, and clinical predictive factors of incomplete response/treatment failure to the standard treatment (prednisone with or without azathioprine) in a well-characterized series of AIH Egyptian patients.

Patients And Methods: Of 49 AIH patients, only 36 patients completed this retrospective cohort study.