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Tumor cells upregulate CCL22 in a STING-dependent manner in response to paracrine factors released by STING-activated myeloid cells and type I interferons.

Immunosuppressive elements within the tumor microenvironment include both regulatory T cells (Tregs) and M2 macrophages. A well-described mechanism of Treg recruitment occurs via the chemokine CCL22, and CCL22 has also recently been implicated in the polarization of tumor-associated macrophages to the M2a subtype. Our lab and others have shown that CCL22 is upregulated in cancer cells following activation of the stimulator of interferon genes (STING). STING triggers immune responses against pathogenic nucleic acids as well as self-DNA mislocalized to the cytoplasm, which can accumulate in canc…

Plant extracellular vesicles as emerging neuroprotective agents for central nervous system disorders.

BACKGROUND: Plant extracellular vesicles (PEVs) have emerged important roles in central nervous system (CNS) disorders. PEVs are nanoscale v … and medicinal plants, contain bioactive molecules such as proteins, lipids, microRNAs (miRNAs) and nucleic acids. These vesicles demonstrate the ability to traverse the BBB through receptor-mediated transport and membrane fusion, delivering therapeutic effects for CNS disorders, including neuroinflammation, ischemic stroke, and gliomas. Their pharmacological b …

AI-designed PNA-peptide chimera overcomes suboptimal binding for dual inhibition of viral RdRp.

The chimera combining the peptide nucleic acids (PNAs) and peptides represent a promising bifunctional strategy by concurrently binding with protein catalytic pocket and its associated RNA template, effectively disrupting protein's function. Conventional designs face challenges due to non-optimized peptide-protein interactions and empirical PNA sequence selection, which lack thermodynamic or computational refinement, compromising selectivity and efficacy. Here, we present an artificial intelligence (AI) and molecular simulations-driven framework for the de novo design of a high-affinity PNA-pe…

Current and Future Role of Circulating DNA in the Diagnosis and Management of Urothelial Carcinoma.

The growing sophistication of tumor molecular profiling has helped to slowly transition oncologic care toward a more personalized approach i … dly refer to the isolation of both cellular and noncellular tumor components including proteins and nucleic acids such as mRNA and circulating free DNA within a liquid sample. Although protein-based testing and testing of circulating tumor cells are options, the bulk of promising research in bladder cancer is investigating the role of plasma-based circulating t …

Exploring the Vertical Transmission of Exosomes in Diagnostic and Therapeutic Targets for Pregnancy Complications.

During pregnancy, the mother-placenta relationship involves intricate and dynamic exchanges. Over the course of gestation, the maternal body encounters numerous fetal materials secreted by the placenta, such as hormones, growth factors, and extracellular vesicles like exosomes. These exosomes are carriers of key biomolecules, including proteins, lipids, nucleic acids (DNA), and microRNA (miRNA), capable of influencing maternal cellular activity. Although the exact functions of placental exosomes during pregnancy remain under investigation, existing research indicates that they contribute signi…

A Photoelectrocatalytic Platform for Sequence-Unrestricted Modification of Oligonucleotide Backbones.

Oligonucleotide-based therapeutics represent a transformative modality for treating genetic disorders, yet their clinical translation is often hindered by poor nuclease stability, limited cellular uptake, and sequence-dependent toxicity. Chemical modification of the phosphodiester backbone is a central strategy to address these challenges. Among these, charge-neutral alkyl phosphonate analogues featuring P─C linkages have attracted considerable attention for their potential to enhance stability and safety. However, general and programmable methods for site-specific installation of diverse alky

A Robust Quantitative Multiplex PCR for T-cell Receptor Repertoire Sequencing from Formalin-Fixed Paraffin-Embedded Samples.

The analysis of the T-cell receptor (TCR) is becoming an increasingly important tool in the study of the tumor microenvironment. Global features of the repertoire, including clonality and diversity, can give important insights into the immunological processes which drive cancer progression or regression, especially in the context of immune checkpoint inhibitors. Specific TCR sequences are increasingly being used as part of the computational or experimental antigen discovery pipeline. However, the clinical samples available from tumors frequently contain poor-quality nucleic acids, making the a…

Priming with DNMT Inhibitors Potentiates PD-1 Immunotherapy by Triggering Viral Mimicry in Relapsed/Refractory NK/T-cell Lymphoma.

UNLABELLED: Anti-PD-1 immunotherapy has demonstrated significant antitumor efficacy in relapsed or refractory NK/T-cell lymphoma (R/R NKTL), … emethylation of endogenous retroviral elements, activating viral mimicry via upregulated endogenous nucleic acids and type I IFN signaling. These findings underscore DNMT inhibitors' role in overcoming PD-1 resistance and support their combination with anti-PD-1 as a promising strategy for R/R NKTL. SIGNIFICANCE: Resistance to anti-PD-1 immunotherapy remains a …

Review of porcine circovirus 3-associated lesions in swine: Challenges and advances in diagnostics.

Porcine circovirus 3 (PCV3) is a recently identified pathogen in swine populations. It is considered a ubiquitous virus and is frequently as … eric arterial plexus, and kidneys. Despite the broad tissue tropism and frequent detection of viral nucleic acids within affected vascular and parenchymal structures, the precise mechanisms underpinning PCV3 pathogenesis remain poorly understood. Diagnosis of PCV3-AD relies on the confluence of characteristic clinical signs, compatible histopathological finding …

Dhx36 deficiency accelerates BMSC senescence and promotes age-related bone loss.

Senescence of mesenchymal stem cells in bone tissue (BMSCs), the primary progenitors of osteoblasts, is a key contributor to age-related osteopenia and osteoporosis. Aged cells exhibit elevated cellular stress and abnormal accumulation of stress granules (SGs), which contain G-quadruplex (G4) structured nucleic acids and G4-binding proteins. Dhx36, a helicase that unwinds G4 structure, may play a protective role in this context. In this study, we investigated the function of Dhx36 in BMSCs and bone homeostasis by silencing Dhx36 expression in vitro and in vivo. Dhx36 deficiency increased SG fo…

The Rare Syndrome Aicardi-Goutières 4: A Case Report and Literature Review.

Aicardi-Goutières syndrome (AGS) is a genetically heterogeneous type of interferonopathy resulting from defects in the processing or sensing of nucleic acids. The AGS phenotype encompasses a broad range of neurological and non-neurological findings. It presents with a congenital or subacute onset, manifesting as microcephaly, spasticity, dystonia, seizures, cortical blindness, and psychomotor retardation in the first year of life. The radiological and laboratory findings of AGS are generally accompanied by intracranial calcification, white matter abnormalities, cerebral atrophy, and cerebrospi…

1H, 13C and 15N chemical shift assignments of Rubella virus macro domain in the free and in the ADPr bound state.

Prokaryotes, eukaryotes, and certain viruses with positive single-stranded RNA genomes are among the forms of life that have been found to p … binding to and hydrolyzing ADP-ribose (ADPr) from ADP-ribosylated substrates including proteins and nucleic acids. Consequently, it represents an attractive pharmacological target. Currently, no inhibitors exist for RuV MD's de-ADP-ribosylation activity, which may play a crucial role in viral replication and pathogenesis, as observed in severe acute respiratory …

Effect of PEG-Induced Liquid-Liquid Phase Separation on DNA-Topotecan Interactions.

Understanding the impact of liquid-liquid phase separation (LLPS) on drug and biological molecules is key to advancing drug delivery and bio … iated LLPS to tune the excited-state dynamics of small molecules and the structural organization of nucleic acids, offering insights into their potential applications in complex molecular environments.

Extracellular Vesicles as Emerging Regulators in Ischemic and Hypertrophic Cardiovascular Diseases: A Review of Pathogenesis and Therapeutics.

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, have emerged as important regulators in specific cardiovascular conditions such as myocardial infarction, atherosclerosis, coronary artery disease, and cardiac hypertrophy. EVs mediate intercellular communication by transferring bioactive cargo such as proteins, lipids, and nucleic acids. EVs influence crucial pathological processes, including inflammation, fibrosis, apoptosis, and cardiac remodeling, contributing to disease progression. This review assessed the therapeutic potential of stem cell-derived EVs…

Oxidative Stress and Skin Diseases: The Role of Lipid Peroxidation.

Lipid peroxidation (LPO) is a biochemical process through which lipids are subjected to a peroxidation reaction in the presence of free radicals. The process can cause alterations in biological membranes and the formation of substances harmful to the body that can form aggregates with proteins and nucleic acids. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) are the main products of LPO. These compounds have cytotoxic and genotoxic properties and contribute to the pathogenesis of various diseases. This research focuses on the correlation between LPO and skin diseases. For some skin disease…

Rapid visual detection of Monkeypox virus by one-step LAMP-CRISPR/Cas12b assay.

BACKGROUND: Monkeypox virus (MPXV) infection has garnered significant global attention due to its rising incidence and substantial public he … ire opening the lid of the reaction tube and could be completed within 40 min using extracted viral nucleic acids, which is faster than real-time quantitative PCR (qPCR). And the results could be interpreted through either real-time fluorescence or naked-eye visualization. The limit of detection (LOD) of the assay was demonstrated to be 6.5 copies per reaction …

Transforming tuberculosis diagnosis with clinical metagenomics: progress and roadblocks.

Tuberculosis (TB) remains a leading global infectious killer, yet traditional diagnostic methods are inadequate. Acid-fast staining suffers … performance is often constrained by low mycobacterial read counts, interference from abundant host nucleic acids, and the inability to distinguish active from latent infection. In addition, the accuracy of drug resistance prediction using mNGS remains limited, and the World Health Organization currently endorses targeted NGS as the preferred sequencing-based a …

Достижения в области нанотехнологии для адресной доставки наркотиков в случае нейродегенеративных заболеваний.

Нейродегенеративные заболевания, в том числе болезни Альцгеймера, Паркинсона и множественный склероз, представляют собой растущую проблему в области здравоохранения ввиду их воздействия на качество жизни и трудностей с их лечением. Эти расстройства связаны с повреждениями мозга и такими барьерами, как барьер для мозга крови (ББД), которые препятствуют эффективному лечению. Нанотехнология, особенно функциональные наночастицы (НП), становится многообещающим инструментом преодоления этих барьеров. Нанопчасти, такие, как липосомы, полимерные микроэлементы и золотые наночастицы (AuNPs), демонстриру

Совпадение в аннотации оригинала
Neurodegenerative diseases, including Alzheimer's, Parkinson's, and multiple sclerosis, are a growing healthcare challenge due to their impa … ion time, and treatment efficacy. Nanocarrier-based systems have demonstrated success in protecting nucleic acids from degradation, improving BBB penetration, and delivering genetic material to target specific brain areas. Exosomes and artificial vesicles also hold promise for their size and biocompatibility. Gold nanoparticles are gaining attention for their n …

Gingival crevicular fluid levels of TLR-9, AIM-2, and ZBP-1 in periodontal diseases.

OBJECTIVES: Toll-like receptor (TLR)-9, may play a role in periodontal disease inflammation. This study measured TLR-9 and its related molecules, absence in melanoma-2 (AIM-2) and Z-DNA-binding protein-1 (ZBP-1), in gingival crevicular fluid (GCF) from patients with varying stages of periodontal disease to assess the role of pathogen-derived nucleic acids in inflammation. MATERIALS AND METHODS: The study comprised 80 participants: 20 with Stage III Grade C periodontitis, 20 with Stage III Grade B periodontitis (P-Stage III-B), 19 with gingivitis, and 21 with periodontal health. Parameters inc…

Serum dsDNA is environmentally contingent.

Psoriasis is a recurrent autoimmune disease characterized by seasonal and latitudinal variations. Double-stranded DNA (dsDNA) is a crucial component of nucleic acids and nucleosomes that provoke innate immune responses. Given the potential influence of climate on immunity and the development of autoimmune diseases, a comprehensive quantitative analysis of dsDNA levels in the population is warranted. In this case-control study conducted from 2016 to 2020, 10,110 psoriasis patients and matched controls from 12 regions in China were included. This study examined variations in serum dsDNA levels b…