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Инженерные экзосомы для целевой нейродегенеративной терапии: инновации в биогенезе, загрузка наркотиков и клинический перевод.

Нейродегенеративные заболевания (НДД), включая болезнь Альцгеймера (AD), болезнь Паркинсона (PD), амиотропический боковой склероз (ALS), болезнь Хантингтона (HD) и множественный склероз (MS), характеризуются прогрессивной нейронной дисфункцией и ограниченными терапевтическими возможностями, в основном из-за ограничительного характера мозгового барьера (BBB). Экзосомы, естественно встречающиеся внеклеточными везиклами (ЭМ), привлекли внимание в качестве инновационных средств доставки наркотиков в силу их внутренней способности пересекать ББД, минимальной иммуногенности, высокой биосопоставимост

Совпадение в аннотации оригинала
Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntin … nicity, high biocompatibility, and capability to carry diverse therapeutic cargos such as proteins, nucleic acids, and small molecules. Furthermore, exosomes can be bioengineered to enhance drug-loading efficiency and targeting specificity, positioning them as a versatile and effective platform for treating NDDs. In this review, we summarize recent advances in …

Loss of DHX36/G4R1, a G4 resolvase, drives genome instability and regulates innate immune gene expression in cancer cells.

G-quadruplexes (G4s) are four-stranded alternative secondary structures formed by guanine-rich nucleic acids and are prevalent across the human genome. G4s are enzymatically resolved by specialized helicases. Previous in vitro studies showed that DEAH-box helicase 36 (DHX36/G4R1/RHAU) has the highest specificity and affinity for G4 structures. Here, by mapping genome-wide DNA double-strand breaks (DSBs), we demonstrate that knockout of DHX36 helicase increases DSB enrichment at G4 sites and that the presence of the G4 motif is a significant mediator of genome instability at regulatory regions.…

The twist-and-squeeze activation of CARF-fused adenosine deaminase by cyclic oligoadenylates.

The recently identified CARF (CRISPR-associated Rossman-fold) family of proteins play a critical role in prokaryotic defense, mediating cOA (cyclic oligoadenylate)-stimulated ancillary immune responses in the type III CRISPR-Cas systems. Whereas most previously characterized CARF proteins contain nucleic acids or protein degradation effectors, a subset of the family, including the CARF-fused adenosine deaminase (ADA) (Cad1), has recently been shown to convert ATP to ITP. The enzymatic mechanism and the activation process of Cad1, however, remain incompletely understood. Here we present biochem…

Integrating acoustic microfluidics with spectroscopic analysis for efficient bacterial lysis and molecular characterisation.

Rapid and efficient bacterial lysis is crucial for point-of-care diagnostics, environmental monitoring, and integrated analytical platforms. … for downstream biomolecular characterisation, revealing enhanced spectral intensities of proteins, nucleic acids, and lipids following lysis. PCR amplification of the 16S rRNA gene and protein quantification further confirmed the integrity and compatibility of lysed samples with standard downstream assays. This streamlined, reagent-free, and scalable approach …

Development of photodynamic therapy in treating oral diseases.

The morbidity of oral disorders, including gingivitis, caries, endodontic-periodontal diseases, and oral cancer, is relatively high globally … en dissolved in the cells. These three components can interact to cause damage to proteins, lipids, nucleic acids, and other biological components within diseased tissues. Herein, we aimed to provide a detailed understanding of PDT and how it can treat oral diseases. Concerns about PDT and potential remedies are also a factor. PDT has been shown in numerous cli …

Extracellular Vesicles Derived from Trypanosomatids: The Key to Decoding Host-Parasite Communication.

Trypanosomatids constitute a family of parasitic protozoa that cause significant human and veterinary diseases that are classified as neglec … y can be found in diverse body fluids that carry biologically active molecules, including proteins, nucleic acids, lipids, and carbohydrates. EVs participate in cell-to-cell communication by delivering their cargo content to recipient cells. Thus, EVs play a role in regulating normal physiological processes, including immune surveillance and tissue repair, as w …

Polyphenols bind G4-Quadruplex structures and act as epigenetic modifiers with anti-cancer effects.

G4-quadruplexes (G4s) are non-canonical structures of nucleic acids that develop in guanine rich regions of DNA and RNA. Due to their presence in oncogenic promoters and telomeres, G4s represent attractive targets in anticancer drug designs. G4s have also been the subject of recent research regarding their role as epigenetic modulators, supporting their participation in epigenetic processes that control gene expression. The development of small compounds that preferentially target G4s have led to a better understanding of how G4s control these mechanisms. Natural products have greatly contribu…

Effect of Glyoxal on Plasma Membrane and Cytosolic Proteins of Erythrocytes.

Glyoxal (GO) is a reactive dicarbonyl derived endogenously from sugars and other metabolic reactions within cells. Numerous exogenous sources of this compound include tobacco smoking, air pollution, and food processing. GO is toxic to cells mainly due to its high levels and reactivity towards proteins, lipids, and nucleic acids. We speculate that glyoxal could be involved in erythrocyte protein damage and lead to cell dysfunction. The osmotic fragility and level of amino and carbonyl groups of membrane proteins of erythrocytes incubated for 24 h with GO were identified. The amount of thiol, am…

Targeting mitochondria: Unveiling novel therapeutic frontiers in sepsis.

Sepsis, a life-threatening condition characterized by organ dysfunction resulting from severe infection, has gained considerable attention f … easing mt damage-associated molecular patterns (DAMPs), i.e., proteins, phospholipids, metabolites, nucleic acids (NA), and reactive oxygen species (ROS). These DAMPs synergize with pathogen-associated molecular patterns (PAMPs) to amplify systemic inflammation and organ injury. Despite advances in understanding mt-driven metabolic and immune dysregulation, tra …

Extracellular Vesicles: a Promising Therapy for Treatment of Central Nervous System Ischemia Reperfusion Injury.

Central nervous system ischemia-reperfusion injury, including cerebral ischemia reperfusion injury (CIRI) and spinal cord ischemia reperfusi … ellular vesicles (EVs) facilitate intercellular communication by transferring proteins, lipids, and nucleic acids, thereby influencing cellular pathways. This review examines the potential of EVs as a promising therapeutic strategy for central nervous system I/R injury. Growing evidence suggests that EVs can mitigate pathological mechanisms in both CIRI and SCI …

Mechanism of DNA and RNA degradation over a photoactive TiO2@SiO2-coated fabric.

Contamination of biochemical diagnostic laboratories with impurity nucleic acids (NAs) strongly affects tests using highly sensitive microbiological methods such as polymerase chain reaction because these NAs can contaminate test samples or reagents and lead to false positive results of analysis. NAs, as biomacromolecules, remain stable on the surface of many materials for a long time, and special treatments are needed to achieve the complete degradation of NAs on the material surface. In this study, we investigated the degradation of DNA fragments, genomic DNA, ribosomal RNA, and small nuclea…

Extracellular vesicles in tumor immunity: mechanisms and novel insights.

Extracellular vesicles (EVs), nanoscale vesicles secreted by cells, have attracted considerable attention in recent years due to their role in tumor immunomodulation. These vesicles facilitate intercellular communication by transporting proteins, nucleic acids, and other biologically active substances, and they exhibit a dual role in tumor development and immune evasion mechanisms. Specifically, EVs can assist tumor cells in evading immune surveillance and attack by impairing immune cell function or modulating immunosuppressive pathways, thereby promoting tumor progression and metastasis. Conv…

Electrochemical molecularly imprinted polymer sensors in viral diagnostics: Innovations, challenges and case studies.

Molecularly imprinted polymers (MIPs) are synthetic equivalent of antibodies and have been widely used in electrochemical sensing as recognition elements. They offer advantages over traditional recognition elements such as antibodies, nucleic acids and aptamers due to their simple synthesis, lower production costs, greater chemical and physical stability, and robust performance in diverse environments. Improved detection techniques and combining MIPs with materials like metal nanoparticles, carbon nanotubes, aptamers, metal organic frameworks, quantum dots, and electrochemically active interna…

The Biophysical Basis for Karyopherin-Dependent Ebola Virus VP24 Nuclear Transport.

Nucleocytoplasmic trafficking is a highly regulated process that allows the cell to control the partitioning of proteins and nucleic acids between the cytosolic and nuclear compartments. The Ebola virus minor matrix protein VP24 (eVP24) hijacks this process by binding to a region on the NPI-1 subfamily of karyopherin alpha (KPNA) nuclear importers. This region overlaps with the activated transcription factor STAT1 binding site on KPNAs, preventing STAT1 nuclear localization and activation of antiviral gene transcription. However, the molecular interactions of eVP24-KPNA5 binding that lead to t…

Dynamic Modulation of IRE1α-XBP1 Signaling by Adenovirus.

The abundant production of foreign proteins and nucleic acids during viral infection elicits a variety of stress responses in host cells. Viral proteins that accumulate in the endoplasmic reticulum (ER) can trigger the unfolded protein response (UPR), a coordinated signaling program that culminates in the expression of downstream genes that collectively restore protein homeostasis. The model pathogen adenovirus serotype 5 (HAdV5) activates the UPR via the signaling axis formed by inositol-requiring enzyme type 1 (IRE1α) and the X-box binding protein 1 (XBP1), a transcription factor required fo…

Evaluation of a concentration method for the recovery of human adenovirus from mineral water, tap water and well water.

Human adenoviruses (HAdV) are frequently excreted in large quantities and persist for extended periods in the environment, posing a signific … d from the filters using sodium hydroxide and concentrated through two centrifugation cycles. Viral nucleic acids were then extracted and detected by real time PCR. Regarding HAdV recovery, the method's efficiency varied depending on the type of analyzed water. However, this method demonstrated a consistent performance, providing reliable results across differe …

Onsite detection of airborne antibiotic-resistant bacteria via Cas9 nickase-triggered amplification reactions.

Antibiotic resistance is a critical global health issue, with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant En … sothermal PCR device was integrated into the system. The CN-TAR assay was validated using synthetic nucleic acids, cultured bacteria, and airborne samples, achieving detection limits of 1.40 copies/μL for MRSA and 1.13 copies/μL for VRE. It demonstrated high sensitivity and rapid turnaround time. Furthermore, its performance was comparable to that of convention …

Harnessing tumor-derived exosomes: A promising approach for the expansion of clinical diagnosis, prognosis, and therapeutic outcome of prostate cancer.

Prostate cancer is the second leading cause of men's death worldwide. Although early diagnosis and therapy for localized prostate cancer hav … e proteins, cytosolic and nuclear proteins, extracellular matrix proteins, lipids, metabolites, and nucleic acids. Exosomes play an essential role in paracrine pathways, potentially influencing Prostate cancer progression through a wide variety of mechanisms. In the present review, we outline and discuss recent progress in our understanding of the role of exoso …

Efficient Cytosolic Delivery of Single-Chain Polymeric Artificial Enzymes for Intracellular Catalysis and Chemo-Dynamic Therapy.

Designing artificial enzymes for in vivo catalysis presents a great challenge due to biomacromolecule contamination, poor biodistribution, a … tion of toxic hydroxyl radicals (·OH), and effective damage of intracellular targets (i.e., lipids, nucleic acids). This work establishes versatile SCNP-based nanoplatforms for developing artificial enzymes for in vivo catalysis.

Immunoregulatory functions and therapeutic potential of natural killer cell-derived extracellular vesicles in chronic diseases.

Extracellular vesicles (EVs) have been proven to play a significant immunoregulatory role in many chronic diseases, such as cancer and immune disorders. Among them, EVs derived from NK cells are an essential component of the immune cell functions. These EVs have been demonstrated to carry a variety of toxic proteins and nucleic acids derived from NK cells and play a therapeutic role in diseases like malignancies, liver fibrosis, and lung injury. However, natural NK-derived EVs (NKEVs) have certain limitations in disease treatment, such as low yield and poor targeting. Concurrently, NK cells ex…