Enhancing non-viral gene delivery to human T cells through tuning nanoparticles physicochemical features, modulation cellular physiology, and refining transfection strategies.

Genetically engineered immune cells hold great promise for treating immune-related diseases, but their development is hindered by technical challenges, primarily related to nucleic acid delivery. Polyethylenimine (PEI) is a cost-effective transfection agent, yet it requires significant optimization for effective T cell transfection. In this study, we comprehensively fine-tuned the characteristics of PEI/DNA nanoparticles, culture conditions, cellular physiology, and transfection protocols to enhance gene delivery into T cells.

CRISPR challenges in clinical developments.

CRISPR-Cas (clustered regularly interspaced short palindromic repeats and associated proteins) is a novel genome editing technology with potential applications in treating diseases. Currently, its use in humans is restricted to clinical trials, although its growth rate is significant, and some have received initial FDA approval. It is crucial to examine and address the challenges for this technology to be implemented in clinical settings.

Insight Into Factors Influencing the Aggregation Process in Wild-Type and P66R Mutant SOD1: Computational and Spectroscopic Approaches.

Disturbances in metal ion homeostasis associated with amyotrophic lateral sclerosis (ALS) have been described for several years, but the exact mechanism of involvement is not well understood. To elucidate the role of metalation in superoxide dismutase (SOD1) misfolding and aggregation, we comprehensively characterized the structural features (apo/holo forms) of WT-SOD1 and P66R mutant in loop IV. Using computational and experimental methodologies, we assessed the physicochemical properties of these variants and their correlation with protein aggregation at the molecular level.

Development of an assay for tetracycline detection based on gold nanocluster synthesis on tetracycline monooxygenase: TetX2@AuNCs.

Gold nanoclusters were synthesized based on the structure of the TetX2 Monooxygenase enzyme to make a nanocluster based on enzyme structure (TetX2@Au-NCs). Kinetic analysis of TetX2@Au-NC nanozyme revealed that the Km values of TetX2@Au-NCs to both HO and TMB chromogenic substrate components are higher in the absence of tetracycline. Additionally, the Vmax of the nanozyme for TMB increased in the presence of tetracycline.

Parameters Optimization for Improving Bioluminescence Inhibition Assay Using Vibrio fischeri Bacteria to Detect Lipopolysaccharide Toxicity in Aquatic Environments.

Bioluminescence inhibition of Vibrio fischeri is a widely used method for toxicity testing in aquatic environments. Certain complex biological contaminants, such as lipopolysaccharide (LPS), can interfere with metabolic pathways during toxicity assays. The standard 15-minute Vibrio fischeri bioluminescence assay has limitations when evaluating and screening water toxicity against complex and emerging chemicals like LPS.

Bisdemethoxycurcumin, a novel potent polyphenolic compound, effectively inhibits the formation of amyloid aggregates in ALS-associated hSOD1 mutant (L38R).

Protein misfolding is a biological process that leads to protein aggregation. Anomalous misfolding and aggregation of human superoxide dismutase (hSOD1) into amyloid aggregates is a characteristic feature of amyotrophic lateral sclerosis (ALS), a neurodegenerative illness. Thus, focusing on the L38R mutant may be a wise decision to comprehend the SOD1 disease process in ALS.

Intelligent guide RNA: dual toehold switches for modulating luciferase in the presence of trigger RNA.

The CRISPR system finds extensive application in molecular biology, but its continuous activity can yield adverse effects. Leveraging programmable CRISPR/Cas9 function via nano-device mediation effectively mitigates these drawbacks. The integration of RNA-sensing platforms into CRISPR thus empowers it as a potent tool for processing internal cell data and modulating gene activity.

Harnessing luciferase chemistry in regulated cell death modalities and autophagy: overview and perspectives.

Regulated cell death is a fate of cells in (patho)physiological conditions during which extrinsic or intrinsic signals or redox equilibrium pathways following infection, cellular stress or injury are coupled to cell death modalities like apoptosis, necroptosis, pyroptosis or ferroptosis. An immediate survival response to cellular stress is often induction of autophagy, a process that deals with removal of aggregated proteins and damaged organelles by a lysosomal recycling process. These cellular processes and their regulation are crucial in several human diseases.

Chirality governs the structure and activity changes of firefly luciferase induced by carbon quantum dots.

Nanobiocatalysis is a novel area integrating various advantages of nanotechnology and enzymatic catalysis. However, great efforts are still needed to fully understand the interactions between nanostructures and enzymes. The biological properties of nano-hybrid enzymes greatly depend on the size and chemical properties of their nano element.

Mutation/metal deficiency in the "electrostatic loop" enhanced aggregation process in apo/holo SOD1 variants: implications for ALS diseases.

Despite the many mechanisms it has created to prevent unfolding and aggregation of proteins, many diseases are caused by abnormal folding of proteins, which are called misfolding diseases. During this process, proteins undergo structural changes and become stable, insoluble beta-sheet aggregates called amyloid fibrils. Mutations/disruptions in metal ion homeostasis in the ALS-associated metalloenzyme superoxide dismutase (SOD1) reduce conformational stability, consistent with the protein aggregation hypothesis for neurodegenerative diseases.

Comprehensive investigation of insulin-induced amyloidosis lesions in patients with diabetes at clinical and histological levels: A systematic review.

Introduction: Insulin-derived amyloidosis (AIns), a skin complication in patients with diabetes, causes impaired insulin absorption. This systematic review aims to get a better understanding of this overlooked condition.

Methods: Comprehensive literature searches were performed in Scopus, PubMed, EMBASE, and Web of Science databases until June 17, 2023.

Plasma acylcarnitines and amino acids in dyslipidemia: An integrated metabolomics and machine learning approach.

Purpose: The Discovery of underlying intermediates associated with the development of dyslipidemia results in a better understanding of pathophysiology of dyslipidemia and their modification will be a promising preventive and therapeutic strategy for the management of dyslipidemia.

Methods: The entire dataset was selected from the Surveillance of Risk Factors of Noncommunicable Diseases (NCDs) in 30 provinces of Iran (STEPs 2016 Country report in Iran) that included 1200 subjects and was stratified into four binary classes with normal and abnormal cases based on their levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and non-HDL-C.Plasma concentrations of 20 amino acids and 30 acylcarnitines in each class of dyslipidemia were evaluated using Tandem mass spectrometry.

A Fluorescent Furan-based Probe with Protected Functional Groups for Highly Selective and Non-Toxic Imaging of HT-29 Cancer Cells and 4T1 Tumors.

Most of the previously reported fluorescent organic probes for cancer cell and tumor imaging have significant limitations including chemical toxicity, structural instability, low Stokes shift value, and the inability for selective accumulations in tumors during in vivo imaging. To overcome the mentioned challenges, we synthesized the fluorescent probes with protected polar functional groups to enhance the non-toxicity nature and increase the selectivity toward tumors. In addition, the structural rigidity of the fluorescent probes was increased by embedding aromatic rings in the probe structure.

Association between ELMO1 gene polymorphisms and diabetic kidney disease: A systematic review and meta-analysis.

Background: Previous research has suggested that the ELMO1 gene may play a role in the development of diabetic kidney disease. Diabetic kidney disease (DKD) is a serious complication of diabetes and the leading cause of chronic kidney disease and end-stage renal disease (ESRD).

Objective And Rationale: This study aim was to systematically review and explore the association between ELMO1 gene polymorphisms and diabetic kidney disease.

Insight into the Predictive Power of Surrogate Diagnostic Indices for Identifying Individuals with Metabolic Syndrome.

Background: This study aimed to assess the diagnostic capability of insulin surrogate measurements in identifying individuals with metabolic syndrome (MetS) and propose applicable indices derived from fasting values, particularly in large study populations.

Methods: Data were collected from the datasets of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS). MetS was defined based on the National Cholesterol Education Program (NCEP) criteria.

A comparative study of structural and catalytic activity alterations in firefly luciferase induced by carbon quantum dots containing amine and carboxyl functional groups.

Despite of growing interest in use of carbon-based nanomaterials as carriers of functional proteins, less attention has been paid to the effects of these nanomaterials on the structure and function of the proteins. In this study, with the aim of shedding light on the mechanisms of interaction between carbon-based nanomaterials and proteins, the interactions of carbon quantum dots (CQDs) containing amine (CQD-NH) or carboxyl groups (CQD-COOH) with Photinus pyralis firefly luciferase enzyme were investigated by experimental and computational approaches. The structural changes and reduction in activity of the luciferase upon treatment with CQDs were experimentally proved.

Implications of ALS-Associated Mutations on Biochemical and Biophysical Features of hSOD1 and Aggregation Formation.

One of the recognized motor neuron degenerative disorders is amyotrophic lateral sclerosis (ALS). By now, several mutations have been reported and linked to ALS patients, some of which are induced by mutations in the human superoxide dismutase (hSOD1) gene. The ALS-provoking mutations are located throughout the structure of hSOD1 and promote the propensity to aggregate.

Metabolomics signature of cardiovascular disease in patients with diabetes, a narrative review.

Objectives: The exact underlying mechanism of developing diabetes-related cardiovascular disease (CVD) among patients with type 2 diabetes (T2D) is not clear. Metabolomics can provide a platform enabling the prediction, diagnosis, and understanding of the risk of CVD in patients with diabetes mellitus. The aim of this review is to summarize the available evidence on the relationship between metabolomics and cardiovascular diseases in patients with diabetes.

FeO@SiO@NiAl-LDH microspheres implication in separation, kinetic and structural properties of phenylalanine dehydrogenase.

FeO@SiO@NiAl-LDH three-components microsphere contains a Fe3O4@SiO2 magnetic core and a layered double hydroxide with nickel cation provide the binding ability to (His)-tagged-protein and exhibits high performance in protein separation and purification. The morphology and chemistry of the synthesized FeO@SiO@NiAl-LDH microspheres were characterized by energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), vibrating sample magnetometer (VSM), Dynamic light scattering (DLS). Purified enzyme was assesed with SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis and intrinsic fluorescence spectroscopy.

Organic-inorganic hybrid nanoflowers as a new biomimetic platform for ROS-induced apoptosis by photodynamic therapy.

We report here a newly and facile synthesis of the phospholipids@gold nanoflowers (AuNFs) from intact cells as a new biomimetic organic-inorganic hybrid. The most appealing feature of this nanostructure is its dual-absorbing peak in near infrared (NIR) and visible region of spectra, which makes them a potential light-sensitive agent for reactive oxygen species (ROS)-induced apoptosis. Here, in contrast to previous studies, proposed nanostructures are synthesized in a one-pot reaction using phospholipids present in living cell membranes (as a donor cell) with detectable micro process of AuNF formation.

Anti-inflammation-based treatment of atherosclerosis using Gliclazide-loaded biomimetic nanoghosts.

In the study, a biomimetic platform for anti-inflammatory-based treatment of atherosclerotic plaque was developed. Gliclazide (GL) as an anti-inflammasome agent was encapsulated in PLGA nanoparticles (NP), which were coated by monocyte membrane using an extrusion procedure. The size and zeta potential of the nanoghost (NG) changed to 292 and - 10 nm from 189.

DNAi-peptide nanohybrid smart particles target BCL-2 oncogene and induce apoptosis in breast cancer cells.

Genomic DNA sequences provide unique target sites, with high druggability value, for treatment of genetically-linked diseases like cancer. B-cell lymphoma protein-2 (BCL-2) prevents Bcl-2-associated X protein (BAX) and Bcl-2 antagonist killer 1 (BAK) oligomerization, which would otherwise lead to the release of several apoptogenic molecules from the mitochondrion. It is also known that BCL-2 binds to and inactivates BAX and other pro-apoptotic proteins, thereby inhibiting apoptosis.

Dual-emissive phenylalanine dehydrogenase-templated gold nanoclusters as a new highly sensitive label-free ratiometric fluorescent probe: heavy metal ions and thiols measurement with live-cell imaging.

Phenylalanine dehydrogenase (PheDH) has been proposed as an ideal protein scaffold for the one-step and green synthesis of highly efficient multifunctional gold nanoclusters. The PheDH-stabilized fluorescent gold nanoclusters (PheDH-AuNCs) with dual emission/single excitation exhibited excellent and long-term stability, high water solubility, large Stokes shift and intense photoluminescence. Selectivity studies demonstrated that the red fluorescence emission intensity of PheDH-AuNCs was obviously decreased in less than 10 min by the addition of mercury, copper, cysteine or glutathione under the single excitation at 360 nm, without significant change in the blue emission of the PheDH-AuNCs.