Immunomodulatory Mechanisms and Therapeutic Potential of Mesenchymal Stem Cells

Stem Cell Reviews and Reports, Journal Year: 2023, Volume and Issue: 19(5), P. 1214 - 1231

Published: April 14, 2023

Abstract Mesenchymal stem cells (MSCs) are regarded as highly promising for allogeneic cell therapy, owing to their multipotent nature and ability display potent varied functions in different diseases. The of MSCs, including native immunomodulation, high self-renewal characteristic, secretory trophic properties, can be employed improve the immune-modulatory MSCs impact most immune by directly contacting and/or secreting positive microenvironmental factors influence them. Previous studies have reported that immunomodulatory role is basically dependent on secretion from MSCs. This review discusses capabilities strategies successfully potential utilization clinical research. Graphical

Language: Английский

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Ursolic Acid Alleviates Neuroinflammation after Intracerebral Hemorrhage by Mediating Microglial Pyroptosis via the NF-κB/NLRP3/GSDMD Pathway

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14771 - 14771

Published: Sept. 30, 2023

The neuroinflammatory response after intracerebral hemorrhage (ICH) causes a large amount of neuronal loss, and inhibiting the inflammatory can improve prognosis. In previous laboratory studies clinical trials, ursolic acid (UA) inhibited response, but whether it be administered to inhibit cerebral is unknown. aim this study was investigate effects hemorrhage. Online databases were used obtain potential therapeutic targets for treatment hemorrhage, possible mechanisms analyzed by KEGG, GO, molecular docking. A rat model established using collagenase, an in vitro constructed adding hemin BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, calcein/PI staining degree microglial M1 polarization, changes levels factors, activation NF-κB pathway, indicators cellular death treatment. addition, phorbol 12-myristate 13-acetate (PMA) activate pathway verify that exerts its anti-neuroinflammatory regulating NF-κB/NLRP3/GSDMD pathway. Network pharmacology bioinformatics analyses revealed may exert on through multiple pathways. Together, vivo experiments showed polarization significantly reduced p-NF-κB, GSDMD-N, cleaved caspase-1, TNF-α, IL-6, IL-1β, which use PMA. Ursolic inhibits pyroptosis via alleviate responses

Language: Английский

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Stroke Related Brain–Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms

Advanced Science, Journal Year: 2024, Volume and Issue: 11(14)

Published: Feb. 2, 2024

Abstract The emergence of acute ischemic stroke (AIS) induced cardiovascular dysfunctions as a bidirectional interaction has gained paramount importance in understanding the intricate relationship between brain and heart. Post AIS, ensuing encompass spectrum complications, including heart attack, congestive failure, systolic or diastolic dysfunction, arrhythmias, electrocardiographic anomalies, hemodynamic instability, cardiac arrest, among others, all which are correlated with adverse outcomes mortality. Mounting evidence underscores intimate crosstalk brain, facilitated by physiological neurohumoral complex networks. primary pathophysiological mechanisms contributing to these severe complications involve hypothalamic‐pituitary‐adrenal (HPA) axis, sympathetic parasympathetic hyperactivity, immune inflammatory responses, gut dysbiosis, collectively shaping stroke‐related brain–heart axis. Ongoing research endeavors concentrated on devising strategies prevent AIS‐induced dysfunctions. Notably, labetalol, nicardipine, nitroprusside recommended for hypertension control, while β‐blockers employed avert chronic remodeling address arrhythmias. However, despite therapeutic interventions, targets remain elusive, necessitating further investigations into this challenge. This review aims delineate state‐of‐the‐art AIS through preclinical clinical research, unraveling their interplay within offering pragmatic suggestions managing

Language: Английский

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Polydopamine(PDA)-coated diselenide-bridged mesoporous silica-based nanoplatform for neuroprotection by reducing oxidative stress and targeting neuroinflammation in intracerebral hemorrhage

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 23, 2024

Oxidative stress (OS) and neuroinflammation are critical pathological processes in secondary brain injury (SBI) after intracerebral hemorrhage(ICH), their intimate interactions initiate aggravate damage. Thus, targeting oxidative could be a promising therapeutic strategy for ICH treatment. Here, we report high-performance platform using polydopamine (PDA)-coated diselenide bridged mesoporous silica nanoparticle (PDA-DSeMSN) as smart ROS scavenger ROS-responsive drug delivery system. Caffeic acid phenethyl ester (CAPE) was blocked the pore of DSeMSN by covering with PDA gatekeeper. PDA-DSeMSN @CAPE maintained high stability underwent reactive oxygen species (ROS)-responsive degradation release. The intelligent nanomaterial effectively eliminated ROS, promoted M1 to M2 microglial conversion suppressed vitro vivo. Importantly, intravenous administration PDA-DSeMSN@CAPE specifically accumulated perihematomal sites demonstrated robust neuroprotection an mouse model biological safety. Taking together, synergistic effect ability scavenging makes it powerful provided new considerations into action improve ICH-induce injury.

Language: Английский

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Therapeutic Role of Microglia/Macrophage Polarization in Intracerebral Hemorrhage

Clinical and Translational Neuroscience, Journal Year: 2025, Volume and Issue: 9(1), P. 4 - 4

Published: Jan. 20, 2025

Intracerebral hemorrhage (ICH) is a significant health problem with high mortality and morbidity rates, partly due to limited treatment options. Hematoma after ICH causes neurological deficits the mass effect. Hemorrhage catalyzes secondary damage, resulting in increased poor prognosis, problems. This review evaluates role of immunotherapeutic approaches based on original full-text articles pathophysiology immunotherapy ICH, emphasis modulation microglia/macrophage polarization M2 subtype. In this review, we concluded that injury progression complex multifaceted. Inflammation plays dominant injuries. Furthermore, cells involved inflammatory process have dual roles pro-inflammatory/destructive anti-inflammatory/healing. While inflammation makes immune system therapeutic target them can modulate Resident microglia (and even macrophages migrating from peripheral source) are important targets for because their initiation phase shaping immunity. Although clinical results remain poor, experimental trial data seem promising deciphering providing

Language: Английский

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Immune cells in intracerebral hemorrhage

Brain Hemorrhages, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Inhibition of C3a/C3aR by SB290157 Attenuates Neuroinflammation via PKC/P38/NLRP3 Signaling Pathway After Intracerebral Hemorrhage

Neurocritical Care, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

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Transcriptome analysis reveals that the injection of mesenchymal stem cells remodels extracellular matrix and complement components of the brain through PI3K/AKT/FOXO1 signaling pathway in a neuroinflammation mouse model

Genomics, Journal Year: 2025, Volume and Issue: 117(3), P. 111033 - 111033

Published: March 22, 2025

Language: Английский

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Ubiquitin Ligases in Control: Regulating NLRP3 Inflammasome Activation

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(3)

Published: March 19, 2025

Ubiquitin ligases play pivotal roles in the regulation of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, a critical process innate immunity and inflammatory responses. This review explores intricate mechanisms by which various E3 ubiquitin exert both positive negative influences on NLRP3 activity through diverse post-translational modifications. Negative assembly is mediated several ligases, including F-box leucine-rich repeat protein 2 (FBXL2), tripartite motif-containing 31 (TRIM31), Casitas B-lineage lymphoma b (Cbl-b), induce K48-linked ubiquitination NLRP3, targeting it for proteasomal degradation. Membrane-associated RING-CH 7 (MARCH7) similarly promotes leading to autophagic degradation, while RING finger (RNF125) induces K63-linked modulate function. Ariadne homolog (ARIH2) targets nucleotide-binding (NBD) inhibiting its (TRIM65) employs dual K48 suppress assembly. Conversely, Pellino2 exemplifies regulator, promoting activation ubiquitination. Additionally, influence other components TNF receptor-associated factor (TRAF3) mediates K63 polyubiquitination apoptosis-associated speck-like CARD (ASC), facilitating regulate caspase-1 DEAH-box helicase 33 (DHX33)-NLRP3 complex formation specific events. Beyond direct regulation, impact broader immune signaling pathways, modulating pattern-recognition receptor responses dendritic cell maturation. Furthermore, they intricately control NOD1/NOD2 receptor-interacting (RIP2), crucial nuclear kappa-light-chain-enhancer activated B cells (NF-κB) mitogen-activated kinase (MAPK) activation. we explore how pathogens, bacteria, viruses, parasites, have evolved sophisticated strategies hijack host machinery, manipulating evade comprehensive analysis provides insights into molecular underlying their implications diseases, offering potential avenues therapeutic interventions inflammasome. In conclusion, emerge as key regulators exhibiting array functions that finely tune Understanding these regulatory not only sheds light fundamental aspects inflammation but also offers disorders infectious diseases.

Language: Английский

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Pink1 deficiency enhances neurological deficits and inflammatory responses after intracerebral hemorrhage in mice

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(2), P. e00317 - e00317

Published: Jan. 23, 2024

Pink1 (PTEN-induced putative kinase 1) is a protein associated with maintaining mitochondrial function and integrity has been reported to mediate neurodegeneration neuroinflammation. While the role of in intracerebral hemorrhage (ICH)-related neurological deficits inflammatory responses not deciphered. Congenic blood was transfused into left corpus striatum construct ICH model C57/BL6 wild-type (WT) Pink1−/− mice. The relative expression Pink1, monocyte chemoattractant protein-1 (MCP-1), macrophage (MIP)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, Cd86, nitric oxide synthase 2 (Nos2), Cd206, arginase 1 (Arg-1), IL-10 detected qRT-PCR, Western blotting, or ELISA. Mouse deficit scores (mNSS) water content were detected, an open-field test performed assay anxiety-like behavior. Remarkably decreased increased MIP-2, IL-1β, MCP-1, TNF-α observed after 12 ​h, 24 48 72 7 ​d post-ICH induction ipsilateral injury hemispheres. deficiency could further up-regulate mNSS scores, brain content, On other hand, decrease number center cross, velocity, total distance traveled open field test. mRNA levels pro-inflammatory (M1) molecules (Cd86, Nos2), down-regulate anti-inflammatory (M2) (Cd206, Arg-1, IL-10). deteriorates ICH, which can be considered as treatment target.

Language: Английский

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