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Global Profiling of Remodeled Subcellular Structures Due to Drug Treatment and Disease.

Cellular biochemistry arises from various interactions between macromolecules, including proteins, nucleic acids, and lipids. These make up membrane-bound organelles, membrane-less compartments, and molecular assemblies and scaffolds. Changes due to stimuli or disease can significantly impact cell fate and metabolism. We recently reported our protocol combining crosslinking and size exclusion chromatography with mass spectrometry (SEC-MS). In this study, we explore global changes to subcellular structure in Ewing sarcoma cell lines or in response to drug treatment. Crosslinking-dependent diffe…

Разоблачение патогенов и загрязнителей: обработка метагеномики для клинической диагностики.

ВВЕДЕНИЕ: Метагеномическая последовательность (mNGS) - нецелевой подход, который последовательность всех нуклеиновых кислот в образце, - стала мощным инструментом обнаружения патогенов и определения характеристик генома. Однако его внедрение в клиническую диагностику остается ограниченным из-за таких технических проблем, как загрязнение и снижение чувствительности, особенно в образцах с низкой биомассой. Мы применили MNGS к 144 клиническим образцам, представляющим собой хронические инфекции, острые инфекции и сопутствующие респираторные инфекции. Для решения проблемы загрязнения мы создали рам

Совпадение в аннотации оригинала
INTRODUCTION: Shotgun metagenomic sequencing (mNGS), an untargeted approach that sequences all nucleic acids in a sample, has emerged as a powerful tool for pathogen detection and genome characterization. However, its implementation in clinical diagnostics remains limited due to technical challenges such as contamination and reduces sensitivity, especially i…

Proteomic advances in extracellular vesicles: unlocking biomarkers for microbial infectious diseases.

INTRODUCTION: Microbial infectious diseases pose a significant threat to global health. Early and accurate pathogen identification directly influences antimicrobial strategies and patient outcomes. Extracellular vesicles (EVs) serve as key mediators of intercellular signaling and can transport nucleic acids and proteins from both host and pathogen sources. Proteomic analysis of EVs captures pathogen activity, host response, and tissue injury, offering a review-focused perspective on biomarker discovery for microbial infectious diseases. AREAS COVERED: This review summarizes the biogenesis and…

A case study of delayed-diagnosed leprosy: advancing diagnosis through MetaPath.

BACKGROUND: Leprosy, a chronic infectious disease caused by Mycobacterium leprae, can lead to sensory deficits, motor impairment, disability, and social stigma, imposing a dual physical and psychological burden on patients. Early diagnosis and standardized treatment are therefore crucial. Metagenomic Capture Technology for Pathology (MetaPath) is a probe-capture-based high-throughput sequencing technology for pathogen nucleic acids, which holds promise for the early detection of Mycobacterium leprae in pathological specimens. CASE SUMMARY: A 78-year-old male presented with erythematous, scaly…

Exploring the antibacterial and antibiofilm potential of graphene nanosheets synthesized from candlenut shell waste.

The rising threat of antibiotic-resistant pathogens necessitates the development of novel antimicrobial agents, and graphene nanomaterials h … t S. aureus and S. enteritidis, respectively. Cell leakage assays revealed a significant release of nucleic acids and proteins, confirming membrane disruption. Time-kill kinetics showed complete elimination of S. aureus within 16 h at 25 μg/mL and rapid eradication of S. enteritidis within 8 h at 25 μg/mL. Biofilm assays demonstrated a significant (p < 0.05) re …

Paclitaxel Nanomedicines: Molecular Mechanisms of Drug Resistance, Tumor Microenvironment-Responsive Delivery, and Translational Challenges.

Paclitaxel (PTX) remains a major component of treatment for solid tumors, but its clinical performance is limited by poor aqueous solubility … ase; tissue penetration and subcellular localization; and co-delivery of PTX with chemosensitizers, nucleic acids, or pathway-directed agents. Molecular simulation and machine learning are considered as tools for formulation optimization and biomarker-guided patient stratification. These approaches can coordinate drug exposure and resistance modulation in precl …

Endogenous Corticosteroid Derived Lipid Nanoparticles (Cortico LNPs) Enable Selective mRNA Delivery to the Spleen.

Lipid nanoparticles (LNPs) have emerged as effective delivery vehicles for nucleic acids. However, conventional LNP formulations face several limitations, including poor endosomal escape and ApoE-mediated liver tropism. Here, a novel class of LNPs, endogenous corticosteroid-derived LNPs (cortico LNPs), is introduced in which the cholesterol component is replaced with endogenous corticosteroids, resulting in redirection from the liver to the spleen. Multiple corticosteroids and their precursors, including corticosterone, 11-deoxycortisol, 11-deoxycorticosterone, progesterone, 11β-hydroxyprogest…

Macromolecular Crowding in Cytoplasm and Cellular Organelles.

A high concentration of diverse macromolecules causes a densely packed environment, influencing both function and structural change of the cell organelles, cytoplasm, and molecules within. The concept of molecular crowding was for the first time introduced in the 70 s but was only accepted at the end of the 90 s. Crowding demonstrates how the high concentration of macromolecules, such as proteins, nucleic acids, and polysaccharides, influences the behavior and interactions of these molecules. This systematic review explored recent literature that impacted the understanding of molecular crowdin…

Best practices in sample management and molecular profiling of cholangiocarcinoma: a practical guide.

INTRODUCTION: Cholangiocarcinoma (CCA) is an uncommon yet aggressive malignancy often diagnosed at advanced stages. Its management is challe … ndling to ensure robust molecular analyses to avoid tissue exhaustion and preserve the integrity of nucleic acids. Employing DNA plus RNA sequencing platforms, supported by molecular tumor boards, is recommended to enhance patient stratification and guide therapeutic decision-making in CCA.

Coincident Fluorescence-Burst Analysis of Actin Cargo Molecules in Secreted Single Diffusing Extracellular Vesicles From Human Induced Pluripotent Stem Cells.

Extracellular vesicles (EVs) mediate cellular communication via cargoes of nucleic acids, proteins, and miRNAs, and play key roles in neurodegeneration. However, quantification of specific cargo changes in EVs is challenging due to their small size and heterogeneity. Here, we develop a two-color fluorescence cross-correlation spectroscopy (FCCS) and coincident-burst analysis platform to quantify actin-enhanced green fluorescent protein and micro red fluorescent protein dual-labeled EVs secreted from human induced pluripotent stem cells in undifferentiated, partially differentiated, and amyloid…

Michael addition drugs and cancer.

Some of the earliest anticancer drugs were alkylating agents, capable of covalently modifying critical cellular nucleophiles in proteins and nucleic acids. For many years, adapting another type of covalent reaction, Michael addition reactions, which involve the nucleophilic attack of a carbon nucleophile on an α,β-unsaturated carbonyl compound, have been explored in designing covalent inhibitors that selectively target cancer-related biomolecules. Numerous natural products demonstrate Michael addition properties, contributing to their bioactivity in antioxidant, anti-inflammatory and anticance…

Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adults.

Classic Hodgkin lymphoma (cHL) exhibits a bimodal age distribution with incidence peaks in adolescents and young adults (AYAs) aged 15-39 ye … development of age-specific prognostic indicators. In addition, advances in our ability to isolate nucleic acids from HRS cells have accelerated our understanding of the molecular alterations in cHL, many of which drive interactions within the TME. Molecular differences in cHL between pediatric/AYA and older adult patients have also emerged. This review summar …

Dual-Cascade Activated DNAzyme Nanoreactor within a Zn-Based MOF for Mitochondrial Gene Regulation.

Gene therapy targeting specific organelle genes crucial for cancer cell survival provides a promising strategy for hepatocellular carcinoma (HCC) therapy. The integration of metal-organic framework nanostructures with catalytic nucleic acids provides a promising route toward precision gene therapy. Herein, we report a dual-cascade DNAzyme nanoreactor constructed from the zeolitic imidazolate framework-90 (ZIF-90), which simultaneously serves as a protective host and a zinc ion reservoir. The framework encapsulates an EGR-1-targeting DNAzyme and is further engineered with lignin, N-acetylgalact…

The power of small RNAs: A comprehensive review on bacterial stress response and adaptation.

Bacteria employ a wide range of RNA-based regulatory systems to adapt to various environmental stressors. Among these, small non-coding RNAs … and intercellular communication. These vesicles transport a complex cargo of proteins, lipids, and nucleic acids, including sRNAs. The transfer of sRNAs through OMVs can modulate the physiology of neighboring bacterial cells as well as host cells, highlighting their role in cross-kingdom signaling. sRNAs serve as versatile and potent regulatory elements that s …

Unlocking the therapeutic potential of tumor-derived EVs in ischemia-reperfusion: a breakthrough perspective from glioma and stroke.

Clinical studies have revealed a bidirectional relationship between glioma and ischemic stroke, with evidence of spatial overlap between the … racellular vesicles, with their characteristic bilayer structure, encapsulate proteins, lipids, and nucleic acids, shielding them from enzymatic degradation by ribonucleases, deoxyribonucleases, and proteases. This structural protection facilitates long-distance intercellular communication in multicellular organisms. In gliomas, EVs are pivotal in intracranial …

Therapeutic and Diagnostic Roles of MSC-Derived Exosomes in Alzheimer's Disease.

PURPOSE: Alzheimer's disease (AD), the leading cause of dementia, is characterized by amyloid-β accumulation, tau hyperphosphorylation, neur … somes. It examines how MSC-exos, as nanosized extracellular vesicles carrying proteins, lipids, and nucleic acids, interact with the central nervous system to modulate disease pathways. FINDINGS: MSC-exos can cross the blood-brain barrier (BBB), deliver neurotrophic factors, modulate microglial activity, enhance amyloid clearance, and support neuronal survival …

Screening and Identification of Novel DNA Aptamer for Targeted Delivery to Injured Podocytes in Glomerular Diseases.

Selective drug delivery to podocytes remains a challenge. Aptamers, nucleic acids that bind specific cells, offer a potential solution, though podocyte-targeting aptamers have not yet been developed. Podocytes stimulated with adriamycin, puromycin aminonucleoside, and high glucose are used to screen an single-stranded DNA (ssDNA) library (10¹⁵ sequences). High-throughput sequencing identifies nucleotide sequences, and the aptamer's affinity, stability, cytotoxicity, uptake, biodistribution (especially to podocyte), target protein and ability to deliver siRNA are evaluated. After 11-14 rounds o…

Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniae.

Klebsiella pneumoniae is the causative agent of a wide range of antibiotic-resistant infections, including nosocomial pneumonia and neonatal sepsis. We investigate here the mechanisms underlying innate immune recognition of this pathogen by focusing on the role of endosomal Toll-like receptors (TLRs), which sense prokaryotic nucleic acids, in comparison with TLR4, which recognizes the cell-wall lipopolysaccharide component. Lack of functional endosomal TLRs made mice more susceptible to pulmonary infection by K. pneumoniae, in association with reduced production of proinflammatory and chemotac…

Treatment of lung diseases via nanoparticles and nanorobots: Are these viable alternatives to overcome current treatments?

CHALLENGES: Respiratory diseases remain challenging to treat, with current efforts primarily focused on managing symptoms rather than mainta … R in addressing challenges in pulmonary drug delivery. These innovations allow targeted delivery of nucleic acids, drugs, or peptides to the pulmonary epithelium with unprecedented accuracy, offering significant potential for improving therapeutic effectiveness in respiratory disorders.

Exosomes in Ocular Health: Recent Insights into Pathology, Diagnostic Applications and Therapeutic Functions.

Exosomes are extracellular vesicles ranging from 30 to 150 nm in diameter that contain proteins, nucleic acids and other molecules. Produced by virtually all cell types, they travel throughout the body until they reach their target, where they can trigger a wide variety of effects by transferring the molecular cargo to recipient cells. In the context of ocular physiology, exosomes play a very important role in embryological development, the regulation of homeostasis and the immune system, which is crucial for normal vision. Consequently, in pathological situations, exosomes also undergo modifi…