Acute liver damage generates age independent microglia morphology changes in mice

Romanian Journal of Morphology and Embryology, Год журнала: 2025, Номер 65(4), С. 679 - 685

Опубликована: Фев. 13, 2025

Non-alcoholic fatty liver disease (NAFLD) has emerged as a silent global epidemic, frequently contributing to systemic inflammation. As the primary immune cells of central nervous system (CNS), microglia undergo morphological changes that serve critical indicators CNS health. In this study, we aimed quantify alterations in microglial morphology within cortex young and aged mice with damage. Our results demonstrated hepatic dysfunction leads significant increase total branch length both (285.79±68.23 μm) animals (268.67±69.06 μm), compared their respective controls (164.07±33.05 μm 140.96±27.18 (p 0.0001). Additionally, damage exhibited mean 5.84±0.66 μm, higher than 2.63±0.19 observed those without injury. The number branches decreased from 6.6±1.2 3.1±1.5 addition, have shown decrease secondary This suggests not only respond CNS-specific injuries but also chronic pathologies like NAFLD. These findings highlight importance better understanding liver–brain axis order understand neuroimmune consequences diseases.

Язык: Английский

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The novel peptide DBCH reduces LPS-stimulated NF-κB/MAPK signaling in BV-2 microglia and ameliorates cognitive impairment in scopolamine-treated mice by modulating BDNF/CREB

Neurochemistry International, Год журнала: 2025, Номер unknown, С. 105946 - 105946

Опубликована: Фев. 1, 2025

Язык: Английский

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Therapeutic gene delivery by mesenchymal stem cell for brain ischemia damage: Focus on molecular mechanisms in ischemic stroke

Cell Biochemistry and Function, Год журнала: 2024, Номер 42(2)

Опубликована: Март 1, 2024

Abstract Cerebral ischemic damage is prevalent and the second highest cause of death globally across patient populations; it as a substantial reason morbidity mortality. Mesenchymal stromal cells (MSCs) have garnered significant interest potential treatment for cerebral damage, shown in stroke, because their potent intrinsic features, which include self‐regeneration, immunomodulation, multi‐potency. Additionally, MSCs are easily obtained, isolated, cultured. Despite this, there number obstacles that hinder effectiveness MSC‐based treatment, such adverse microenvironmental conditions both vivo vitro. To overcome these obstacles, naïve MSC has undergone modification processes to enhance its innate therapeutic qualities. Genetic preconditioning (with medications, growth factors, other substances) two main categories into techniques can be separated. This field advanced significantly still attracting attention innovation. We examine cutting‐edge methods preserving even improving natural biological functions relation adhesion, migration, homing target site, survival, delayed premature senescence. address use genetically altered stroke‐induced damage. Future strategies result addressing difficulties associated with also discussed.

Язык: Английский

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Circular RNAs Mediate the Effects of Dietary Tryptophan on the Transformation of Muscle Fiber Types in Weaned Piglets

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(15), С. 8595 - 8605

Опубликована: Апрель 9, 2024

The nutritional composition of the diet significantly impacts overall growth and development weaned piglets. current study aimed to explore effects underlying mechanisms dietary tryptophan consumption on muscle fiber type transformation during weaning period. Thirty piglets with an average body weight 6.12 ± 0.16 kg were randomly divided into control (CON, 0.14% Trp diet) high (HT, 0.35% Trp) groups maintained respective for 28 days. HT group exhibited highly significant improvements in performance increased proportion fast fibers. Transcriptome sequencing revealed potential contribution differentially expressed circular RNAs toward myofiber types regulation expression related genes by targeting microRNAs, miR-34c miR-182, further regulate transformation. In addition, 145 DE circRNAs identified as potentially protein-encoding, encoded proteins associated a conclusion, greatly advances refines our understanding regulatory networks piglet also contributes optimization formulation.

Язык: Английский

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Galangin’s Neuroprotective Role: Targeting Oxidative Stress, Inflammation, and Apoptosis in Ischemic Stroke in a Rat Model of Permanent Middle Cerebral Artery Occlusion

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 1847 - 1847

Опубликована: Фев. 21, 2025

The rising incidence of ischemic stroke poses significant health and healthcare burdens. Given the limitations current therapeutic options, there is increasing interest in exploring potential galangin, a natural flavonoid compound, as treatment for stroke. This study aimed to evaluate neuroprotective effects underlying mechanisms galangin mitigating oxidative stress, inflammation, apoptosis rat model permanent cerebral ischemia. Sixty male Wistar rats were divided into six groups: control; right middle artery occlusion (Rt.MCAO) with vehicle; Rt.MCAO piracetam, synthetic compound known cognitive enhancer; administered at doses 25, 50, 100 mg/kg body weight. Neurological deficit scores, brain edema, neuronal density, microglial morphology assessed along activity myeloperoxidase (MPO), marker superoxide dismutase (SOD). Additionally, expression key markers inflammation apoptosis, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), Bcl-2-associated X protein (Bax), B-cell lymphoma-extra large (Bcl-XL), caspase-3, was analyzed elucidate mechanisms. results demonstrated that significantly improved neurological reduced enhanced attenuated activation, decreased MPO activity, increased SOD both cortex hippocampus, highlighting its potential. These linked modulation inflammatory apoptotic pathways. Specifically, IL-6, COX-2, Bax, caspase-3 while levels anti-apoptotic Bcl-XL. In conclusion, demonstrates promise agent by suppressing thereby improving outcomes. However, clinical trials are required validate these preclinical findings confirm galangin’s efficacy humans.

Язык: Английский

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Remote Organ Damage Induced by Stroke: Molecular Mechanisms and Comprehensive Interventions

Antioxidants and Redox Signaling, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Significance: Damage after stroke is not only limited to the brain but also often occurs in remote organs, including heart, lung, liver, kidney, digestive tract, and spleen, which are frequently affected by complex pathophysiological changes. The organs human body closely connected, signals transmitted through various molecular substances could regulate changes of organs. Recent Advances: latest studies have shown that inflammatory response plays an important role organ damage stroke, can aggravate activating oxidative stress, sympathetic axis, hypothalamic disturbing immunological homeostasis. Remote cause brain, aggravating damage. Critical Issues: Therefore, in-depth exploration mechanisms adopting corresponding comprehensive intervention strategies become necessary reduce promote protection. Future Directions: strategy involves multifaceted treatment methods such as inflammation regulation, antioxidants, neural stem cell differentiation. It provides a promising alternative for recovery patients inspiration future research treatment. interconnected at level. Only levels we save protect greatest extent. Antioxid. Redox Signal. 00, 000-000.

Язык: Английский

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Neuroprotective mechanisms of microglia in ischemic stroke: a review focused on mitochondria

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Апрель 1, 2025

Язык: Английский

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Neuronal cathepsin S increases neuroinflammation and causes cognitive decline via CX3CL1‐CX3CR1 axis and JAK2‐STAT3 pathway in aging and Alzheimer's disease

Aging Cell, Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

Abstract Aging is an intricate process involving interactions among multiple factors, which one of the main risks for chronic diseases, including Alzheimer's disease (AD). As a member cysteine protease, cathepsin S (CTSS) has been implicated in inflammation across various diseases. Here, we investigated role neuronal CTSS aging and AD started by examining expression hippocampus neurons mice identified significant increase, was negatively correlated with recognition abilities. Concurrently, observed elevation concentration serum elderly people. Transcriptome fluorescence‐activated cell sorting (FACS) results revealed that overexpression aggravated brain inflammatory milieu microglia activation to M1 pro‐inflammatory phenotype, chemokine C‐X3‐C‐motif ligand 1 (CX3CL1)—chemokine receptor (CX3CR1) axis janus kinase 2 (JAK2)—signal transducer activator transcription 3 (STAT3) pathway. CX3CL1 secreted acts on CX3CR1 microglia, our first time neuron neuron–microglia “crosstalk.” Besides, elevated regions patients, hippocampus. Utilizing selective inhibitor, LY3000328, rescued AD‐related pathological features APP/PS1 mice. We further noticed increased B (CTSB) activity, but decreased L (CTSL) activity microglia. Overall, provide evidence can be used as biomarker plays regulatory roles through modulating neuroinflammation process.

Язык: Английский

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Novel Hypochlorous Acid-Activated Near-Infrared Probe Monitors the Dynamic Changes of Myeloperoxidase Activity in Ischemic Brain

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Myeloperoxidase (MPO) contributes to the progression of ischemic damage. To fully understand MPO biology, highly sensitive and specific probes that can trace activity endogenous fluxes are indispensable. Here, we developed two hypochlorous acid (HClO)-activated near-infrared image in a noninvasive manner. The probe MPO-NIR-II could track MPO-induced HClO real time situ upon various stimuli with high sensitivity specificity. Furthermore, monitor by vivo fluorescence imaging confocal laser scanning microscopy mice stroke. Moreover, high-content screening system for inhibitors was established combining MPO-overexpressed cells mouse brain slices stroke, candidate compound AZD5904 found effectively attenuate injury. Overall, this work provides versatile tool holds great promise visualizing ischemia.

Язык: Английский

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Microglial Annexin A3 Downregulation Alleviates Ischemic Injury by Inhibiting NF-κB/NLRP3-mediated Inflammation

Inflammation, Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

Microglial inflammation is a hallmark of ischemic stroke. Annexin A3 (ANXA3) expressed in microglia and plays detrimental role However, the ANXA3 microglial after stroke unclear. In this study, an model was established mice via middle cerebral artery occlusion (MCAO). The adeno-associated virus shANXA3 (AAV-shANXA3) injected into ipsilateral cortex lesion, infarction volume, neurological score, neuronal injury were examined. Moreover, primary transfected with lentivirus (LV-shANXA3) subjected to oxygen–glucose deprivation (OGD). Neuron viability lactose dehydrogenase (LDH) levels neurons cocultured analyzed. Additionally, activation ANXA3, p-NF-κB, NLRP3 downstream proteins inflammasome (cleaved caspase-1, N-GSDMD IL-1β) expression measured. We found that increased knockdown reduced mitigated deficits, alleviated injuries. ameliorated p-NF-κB inhibited signaling. Furthermore, upregulation resulted decreased IκBα levels, whereas downregulation levels. Notably, blocked neuroprotective effects AAV-shANXA3 against injury. conclusion, alleviates by inhibiting NF-κB/NLRP3-mediated inflammation, which indicates may be potential therapeutic target for

Язык: Английский

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