Результаты поиска

Exosomes in Alzheimer's disease: neuroinflammation mitigation via immune modulation and inflammatory pathway targeting.

Alzheimer’s disease (AD) progression is tightly linked to neuroinflammation driven by central-peripheral immune imbalance, with microglial/astrocytic activation, blood-brain barrier disruption, and cytokine dysregulation forming a vicious cycle. Exosomes, as nanoscale extracellular vesicles, emerge as potent modulators by crossing the blood-brain barrier and delivering functional cargos (miR-146a, miR-124, TREM2, IL-10) to target immune and neuronal cells. They induce M2 microglial polarization, inhibit A1 astrocyte transformation, and balance Treg/Th17 subsets, while suppressing NF-κB and NLR

CircFRRS1 drives neuroinflammation through the miR-27a-3p/TLR4 pathway after deep hypothermic circulatory arrest.

Neurologic injury remains a critical complication of deep hypothermic circulatory arrest (DHCA) in aortic arch surgery, with neuroinflammation driven by multiple factors in its pathogenesis. While circular RNAs (circRNAs) are known to modulate inflammatory responses, their specific role in DHCA-associated brain injury has not been established. In this study, we demonstrated that circFRRS1 exacerbates hippocampal neuroinflammation via the miR-27a-3p/TLR4 axis through integrated in vivo and in vitro approaches. In a rat model of DHCA, machine learning-based motion sequencing (MoSeq) identified d

HIF-1α translation mediated by PKCδ facilitates RSV-induced production of innate inflammatory cytokines in vitro and in vivo.

A cytokine storm caused by respiratory syncytial virus (RSV) significantly influences the progression of pneumonia and bronchiolitis. It is essential to comprehend the underlying mechanism of the RSV-triggered cytokine storm to effectively manage RSV. Hypoxia-inducible factor-1 Alpha (HIF-1α) plays a pivotal role in innate immunity. It is known that RSV enhances HIF-1α expression, but the molecular mechanism of RSV-induced HIF-1α expression and its role in the production of innate inflammatory cytokines during RSV infection are not fully understood. Our research demonstrates that RSV infection

The neuroimmune-glutamate hypothesis of addiction.

Addictive drugs impact corticostriatal glutamate signaling and have immunomodulatory effects which may underlie drug-associated behaviors during different phases of the addiction cycle. Here we hypothesize that glutamate dyshomeostasis induced by addictive drug use and withdrawal is heavily orchestrated by the neuroimmune system. We systematically define how drug-induced pathologies within the nucleus accumbens (NA) glutamate tripartite synapse are tightly regulated by neuroimmune signaling. Targets within the neuroimmune system represent a novel approach that can be leveraged for clinical stu

Tinosinenside A ameliorates Alzheimer's disease-related pathology in APP/PS1 mice, accompanied by reduced neuroinflammation and altered microglial phenotype-associated marker expression.

Tinospora sinensis (Lour.) Merr. has traditionally been used for its anti-inflammatory properties. Tinosinenside A (Tis A), a major sesquiterpene glycoside isolated from this plant, has shown neuroprotective activity; however, its effects on Alzheimer's disease (AD)-related neuroinflammation remain unclear. This study evaluated the effects of Tis A on behavioral impairment, neuroinflammation, and amyloid-β (Aβ) pathology in APPswe/PSEN1dE9 (APP/PS1) mice. APP/PS1 mice received oral Tis A for 6 months and were evaluated at 11 months of age using behavioral, histopathological, biochemical, and m

Decoding the molecular mechanisms of pyroptosis and its therapeutic development prospects.

Pyroptosis is an emerging form of inflammatory programmed cell death primarily mediated by the gasdermin protein family, characterized by cell swelling, membrane pore formation, and the release of pro-inflammatory cytokines such as IL-1β and IL-18. This mode of cell death has garnered significant attention due to its critical involvement in a variety of diseases, including cancer, cardiovascular disorders, autoimmune diseases, and metabolic syndromes, positioning it as a promising therapeutic target. Despite advances, the complexity of pyroptosis regulation and its dual roles in disease pathog

Совпадение в полном тексте источника
… Activation of inflammasomes and pyroptosis signaling Inflammasomes are cytosolic multiprotein complexes that serve as critical innate immune sensors detecting PAMPs and DAMPs. … Notably, non-canonical inflammasome activation can also promote secondary activation of the canonical NLRP3 inflammasome, linking the two pathways functionally ( Wu J. et al., 2023 ). …

Nanoimmunomodulation for cartilage repair in osteoarthritis: reprogramming the inflammatory joint microenvironment.

Osteoarthritis is a whole-joint disease characterized by persistent inflammation, immune dysregulation, oxidative stress, cellular senescence, and impaired cartilage repair. Current treatments remain largely symptomatic, underscoring the need for disease-modifying strategies that can reshape the pathological joint microenvironment. Nanoimmunomodulation offers a promising approach by combining targeted intra-articular delivery, controlled release, biomimetic design, and immune reprogramming. In this Review, we discuss how nanoplatforms, including polymeric nanoparticles, lipid vesicles, inorgan

Thioredoxin-interacting protein in fibrotic diseases: Mechanisms and therapeutic strategies.

Thioredoxin-interacting protein (TXNIP) critically regulates cellular redox homeostasis. It drives multi-organ fibrosis by integrating oxidative stress, inflammation, metabolic dysregulation, and autophagic dysfunction. TXNIP contributes to organ-specific fibrotic responses in the liver, kidney, heart, and lung through multiple core signaling pathways, including the NLRP3 inflammasome, TGF-β1/Smad, NF-κB, and mTOR cascades. Notably, TXNIP exhibits cell- and organ-specific dual regulatory characteristics during fibrogenesis, adding further complexity to its mechanistic involvement. In recent ye

Modulatory Effects of Chrysin on Cadmium-Induced Hepatotoxicity and Testicular Injury in Rats.

Chrysin (CHR), 5,7-dihydroxyflavone, is a natural flavonoid found in many plant extracts possessing multiple medicinal effects, including anti-inflammatory and antioxidant properties. The aim of this study was to verify the protective role of CHR on testicular and hepatic injury induced by cadmium (Cd). Adult male Sprague Dawley rats were given CdCl2 (3 mg/kg, ip) for 5 days and CHR effect was evaluated using two doses (75 and 150 mg/kg/orally). Administration of CHR showed ameliorative effects against both testicular and hepatic injury. It increased sperm quality and testosterone levels, in a

A surface-mediated hydrogel patch for localized CRISPR genome editing in inflammatory wound therapy.

The NLRP3 inflammasome is a central driver of inflammatory tissue injury and delayed repair in bacteria-infected wounds, yet local genome editing in such lesions remains limited by nonspecific release and off-target exposure. Here, we report a pH-gated surface-mediated hydrogel patch for infection-responsive delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes. Rather than embedding the cargo within the bulk matrix, polymer-coated NLRP3-targeting RNPs are reversibly anchored on the hydrogel surface, enabling localized presentation under physiological conditions and rapid detachment in the

Inhibition of Striatal miR-141-3p Ameliorates Cognitive Deficits and Neuroinflammation in an ADHD Animal Model.

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity that may persist into adulthood. Emerging evidence suggests that microRNAs (miRNAs) contribute to ADHD pathogenesis, but the role of miR-141-3p remains unclear. This study investigated the effects of miR-141-3p inhibition on ADHD-like behaviors in spontaneous hypertensive rats (SHRs). Methods: We used RT-qPCR, immunoblotting, immunohistochemistry, ELISA, and a Y-maze test to assess molecular and behavioral changes after stri

The Evolving Therapeutic Landscape of Gallic Acid: A Review of Mechanistic Insights and Clinical Potential.

Gallic acid (GA), a plant-derived phenolic compound, is evolving from a general antioxidant into a specific molecular modulator and a functional building block for advanced biomedical materials. This review synthesizes recent insights underpinned by GA's "redox duality"-its capacity to act as either a radical scavenger or a pro-oxidant. In metabolic disorders, GA reprograms cellular machinery by modulating the miR-709/Nrf2 axis, enhancing LDL clearance via LDLR/PCSK9, and targeting the incretin system. In oncology, GA exhibits context-dependent toxicity, acting as a selective pro-oxidant to in

Macrophage-Specific SPP1 Contributes to Pressure Overload-Induced Cardiac Dysfunction and Maladaptive Remodeling.

Cardiac macrophages display remarkable functional plasticity via heterogeneous subpopulations and a dynamic secretome, orchestrating key regulatory events during pressure overload-induced myocardial remodeling. However, the specific pathogenic subsets and their core regulatory mechanisms remain insufficiently defined. In this study, we identified a pathogenic secreted phosphoprotein 1 (SPP1)-expressing macrophage subset that emerges early after transverse aortic constriction. Myeloid-specific deletion of Spp1 potently attenuated transverse aortic constriction-induced cardiac inflammation, path

Research progress on the role of CD14 in osteoarthritis.

Osteoarthritis (OA) is a complex degenerative disease centered on inflammation and involving multi-cellular cooperation, with a continuously rising global burden. Current therapeutic measures mainly focus on symptom relief, slowing progression, and end-stage joint arthroplasty; no disease-modifying or reversal agent is yet available, underscoring the urgent need to dissect the inflammatory driving mechanisms and identify effective intervention targets. As a pattern recognition receptor, CD14 is highly expressed on synovial macrophages in the OA microenvironment. It recognizes endogenous damage

Neuroinflammation and peripheral targeting: formulation-based strategies for modulating the neuroimmune axis in diabetic peripheral neuropathy.

INTRODUCTION: Diabetic peripheral neuropathy (DPN) is a common and disabling complication of diabetes that is largely treated symptomatically. Chronic neuroinflammation in the peripheral nerve, dorsal root ganglion, and blood-nerve barrier (BNB) may contribute to disease progression, making the peripheral neuroimmune interface a potential therapeutic target. AREAS COVERED: A literature search of PubMed/MEDLINE and Google Scholar was conducted for January 2005-July 2026, supplemented by reference-list hand-searching and prioritization of recent studies. This review examines neuroinflammatory m

DNA Sensing Pathways in Innate Immunity: Implications for Alzheimer's Disease Progression and Therapy.

DNA sensors are emerging regulators of innate immune activation in Alzheimer's disease (AD). In addition to detecting microbial DNA, these pattern-recognition receptors can respond to cytosolic or endosomal self-DNA generated by DNA damage, mitochondrial dysfunction, impaired DNA repair, cellular stress, or neuronal injury. Aberrant activation of DNA-sensing pathways may amplify neuroinflammation through type I interferon (IFN-I) signaling, inflammasome activation, pyroptosis, and microglial dysfunction, thereby contributing to amyloid pathology, tau-related inflammation, synaptic loss, and co

Discovery of anti-glaucoma agents with dual hCA II inhibitory and nitric oxide-releasing activity and their neuroprotective effects.

Glaucoma-related vision loss is driven by intraocular pressure (IOP)-induced neuronal apoptosis, and current IOP-lowering therapies often incompletely prevent optic nerve damage. Therefore, the development of drugs that combine IOP regulation with neuroprotection holds significant clinical importance. In this study, we designed a series of novel bifunctional anti-glaucoma agents possessing both carbonic anhydrase II (CA II) inhibitory and nitric oxide (NO)-releasing activities. These compounds achieve synergistic IOP lowering by suppressing aqueous humor (AH) production through CA II inhibitio

Pattern recognition receptor signaling in otitis media: immune crosstalk and pathogenic mechanisms.

Otitis media (OM) remains a prevalent and multifactorial inflammatory disease of the middle ear, especially in pediatric populations. The immune system, particularly pattern recognition receptors (PRRs), plays a central role in detecting microbial pathogens and initiating host defenses. TLR2 and TLR4 mediate bacterial clearance but exhibit subtype-specific dysregulation in chronic OM forms. NOD1, NOD2, and NLRP3 modulate intracellular pathogen sensing and inflammasome activation, while RIG-I governs antiviral immunity. C-type lectin receptors (CLRs) are emerging as modulators of both innate an

Metabolic Dysregulation and Oxidative Stress in Diabetic Retinopathy: Glycogen Metabolism, Mitochondrial Dysfunction, and Antioxidant Defences.

Diabetic retinopathy (DR) is a major cause of preventable visual impairment and develops through intertwined metabolic, oxidative, inflammatory, and neurovascular disturbances. This review examines how chronic hyperglycaemia disrupts retinal glucose handling and redox homeostasis, with particular emphasis on glycogen metabolism as an underappreciated contributor to disease progression. Pathological glycogen accumulation in retinal amacrine cells and the retinal pigment epithelium may arise through altered glycogen synthase localisation and glucose-6-phosphate-dependent activation, potentially

Mitochondrial DNA release via VDAC1 in keratinocytes: a key driver of innate immunity and vitiligo pathogenesis.

Vitiligo is an autoimmune depigmenting disorder in which oxidative stress is considered a critical trigger of innate immune activation. Although keratinocytes are increasingly recognized as key contributors to disease progression, the mechanism by which they sense and propagate oxidative stress signals has remained unclear. Here, we identify mitochondrial DNA (mtDNA) release as a pivotal event linking oxidative stress to immune activation in keratinocytes. We demonstrate that hydrogen peroxide induces a sequential mitochondrial membrane remodeling process, in which mitochondrial permeability t