The mechanism of intestinal microbiota regulating immunity and inflammation in ischemic stroke and the role of natural botanical active ingredients in regulating intestinal microbiota: A review

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 157, P. 114026 - 114026

Published: Nov. 25, 2022

Intestinal microbiota is a unique ecosystem, known as the "second genome" of human beings. With widespread application next generation sequencing (NGS), especially 16 S rRNA and shotgun sequencing, numerous studies have shown that dysregulation intestinal associated with many central nervous system diseases. Ischemic stroke (IS) cerebrovascular disease high morbidity mortality. Brain damage in IS affects function, dysfunction further aggravates brain damage, forming vicious circle mutual interference pathology. The microbiota-gut-brain axis study based on has opened up broader ideas for exploring its pathogenesis risk factors, also provided more possibilities selection therapeutic targets this type drug. This review discussed NGS technology research progress recent years, systematically sorts out literature relationship between ischemic microbiota. It starts characteristics axis' bidirectional regulation, respectively discusses factors under imbalance physiological pathological changes after IS, summarizes related targets, order to provide reliable reference treatment from In addition, natural botanical active ingredients achieved good results regulating homeostasis gut microbiota, providing new evidence studying potential therapies axis.

Language: Английский

---

BRG1 alleviates microglial activation by promoting the KEAP1-NRF2/HO-1 signaling pathway and minimizing oxidative damage in cerebral ischemia–reperfusion

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 119, P. 110201 - 110201

Published: May 10, 2023

BRG1 is a key factor in the process of apoptosis and oxidative damage; however, its role pathophysiology ischemic stroke unclear. Here, we discovered that during middle cerebral artery occlusion (MCAO) reperfusion mice, microglia were significantly activated cortex infarct area, expression was increased mouse MCAO/R model, peaking at 4 days. In subjected to OGD/R, peaked 12 h after reoxygenation. After stroke, vitro changing levels greatly altered activation production antioxidant pro-oxidant proteins. Knocking down inflammatory response, promoted microglial activation, decreased NRF2/HO-1 signaling pathway stroke. contrast, overexpression dramatically reduced activation. Our research reveals reduces postischemic damage via KEAP1-NRF2/HO-1 pathway, protecting against brain ischemia/reperfusion injury. Using as pharmaceutical target inhibit responses reduce may be unique way explore techniques for treatment other cerebrovascular illnesses.

Language: Английский

---

Identification of immune-associated genes in vascular dementia by integrated bioinformatics and inflammatory infiltrates

Heliyon, Journal Year: 2024, Volume and Issue: 10(4), P. e26304 - e26304

Published: Feb. 1, 2024

ObjectiveDysregulation of the immune system plays a vital role in pathological process vascular dementia, and this study aims to spot critical biomarkers infiltrations dementia employing bioinformatics approach.MethodsWe acquired gene expression profiles from Gene Expression Database. The data were analyzed using method identify candidate immune-related central genes for diagnosis dementia. diagnostic value nomograms Receiver Operating Characteristic (ROC) curves evaluated. We also examined VaD hub genes. Using database potential therapeutic drugs, we predicted miRNA lncRNA controlling Hub Immune cell infiltration was initiated examine dysregulation dementia.Results1321 included combined dataset, 2816 DEGs GSE122063. Twenty found differential analysis co-expression network analysis. PPI design functional enrichment done as main subject. To create nomogram evaluating value, four core chosen by machine learning. All putative center have solid (AUC ranged 0.81 0.92). Their high confidence level became unquestionable validating each different dataset. According GeneMANIA GSEA investigations, pathophysiology is strongly related inflammatory responses, drug reactions, nervous degeneration. used construct ceRNA that includes three miRNAs, 90 lncRNA, therapeutics. cells with varying found.ConclusionUsing bioinformatic techniques, our research identified (HMOX1, EBI3, CYBB, CCR5). Our confirms these onset progression at infiltration. It predicts RNA regulatory pathways control progression, which may provide ideas treating clinical disease.

Language: Английский

---

Neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epilepsy in rats and its underlying mechanisms

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Feb. 14, 2024

Abstract Introduction Epilepsy is a common neurological disorder that presents with challenging mechanisms and treatment strategies. This study investigated the neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epileptic rats explored its potential mechanisms. Methods Lithium pilocarpine was used to induce an model in rats, seizure symptoms cognitive function were evaluated. The Racine scoring method, electroencephalography, Morris water maze test assess severity learning memory functions group. Additionally, immunohistochemistry Western blot techniques analyze protein expression levels morphological changes glutamate receptor 2 (GluR2; GRIA2), BAX, BCL2 hippocampi Results First, it confirmed group consistent features epilepsy. Furthermore, these demonstrated decreased test. gene GluR2 significantly reduced. Quinpirole delayed onset mortality rate after induction seizure. electroencephalography showed significant decrease frequency spike waves. In test, from shorter latency period reach platform increased number crossings through target quadrant. Network pharmacology analysis revealed close association between as well involvement cAMP signaling pathway, cocaine addiction, dopaminergic synapses. resulted denser arrangement more regular morphology granule cells BAX BCL2. Conclusion current exerted rat induced by pilocarpine. found not only alleviated rats' symptoms, but also improved their abilities. improvement linked modulation GLUR2, These findings provided clues would be important for further investigation therapeutic underlying epilepsy treatment.

Language: Английский

---

Multiplexing light-inducible recombinases to control cell fate, Boolean logic, and cell patterning in mammalian cells

Science Advances, Journal Year: 2025, Volume and Issue: 11(19)

Published: May 9, 2025

Light-inducible regulatory proteins are powerful tools to interrogate fundamental mechanisms driving cellular behavior. In particular, genetically encoded photosensory domains fused split can tightly modulate protein activity and gene expression. While light-inducible systems have performed well individually, few multichromatic orthogonal regulation exist in mammalian cells. The design space for circuits is limited by the small number of orthogonally addressable optogenetic switches types effectors that be actuated them. We developed a library red recombinases directed patterned myogenesis mesenchymal fibroblast-like cell line. To address (LIDs) responding unique excitation spectra, we multiplexed with our “Boolean logic arithmetic through DNA excision” (BLADE) platform. Multiplexed will transformative understanding role multiple interacting genes their spatial context endogenous signaling networks.

Language: Английский

---

Traditional herbal formula Jiao-tai-wan improves chronic restrain stress-induced depression-like behaviors in mice

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 153, P. 113284 - 113284

Published: June 17, 2022

Jiao-tai-wan (JTW) has been often used to treat insomnia and diabetes mellitus. Recent studies found its antidepressant activity, but the related mechanism is not clear. This study evaluate therapeutic effects of JTW on chronic restraint stress (CRS)-induced depression mice explore potential mechanisms.CRS was set up a model. Mice in different groups were treated with 0.9 % saline, fluoxetine. After last day CRS, behavioral tests conducted. The levels neurotransmitters, inflammatory cytokines HPA axis index detected protein expressions NLRP3 inflammasome complex determined. H&E, NISSL, TUNEL immunofluorescence staining observe histopathological changes activation microglia astrocytes. mechanisms explored via network pharmacology verified by Western blot.The assessment liver kidney function showed that non-toxic. Behavioral proved can effectively ameliorate depression-like symptoms CRS mice, which may be inhibition activation. also improve state hyperactivity protective effect CRS-induced hippocampal neurons damage. analysis results blot suggested MAPK signaling pathway.Our findings indicated exert inhibiting improving state, pathway involved.

Language: Английский

---

Bioelectricity in Developmental Patterning and Size Control: Evidence and Genetically Encoded Tools in the Zebrafish Model

Cells, Journal Year: 2023, Volume and Issue: 12(8), P. 1148 - 1148

Published: April 13, 2023

Developmental patterning is essential for regulating cellular events such as axial patterning, segmentation, tissue formation, and organ size determination during embryogenesis. Understanding the mechanisms remains a central challenge fundamental interest in developmental biology. Ion-channel-regulated bioelectric signals have emerged player of mechanism, which may interact with morphogens. Evidence from multiple model organisms reveals roles bioelectricity embryonic development, regeneration, cancers. The Zebrafish second most used vertebrate model, next to mouse model. zebrafish has great potential elucidating functions due many advantages external transparent early embryogenesis, tractable genetics. Here, we review genetic evidence mutants fin-size pigment changes related ion channels bioelectricity. In addition, cell membrane voltage reporting chemogenetic tools that already been or be implemented models. Finally, new perspectives opportunities research are discussed.

Language: Английский

---

The discovery of the new mechanism: Celastrol improves spinal cord injury by increasing cAMP through VIP-ADCYAP1R1-GNAS pathway

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115250 - 115250

Published: July 31, 2023

Spinal cord injury (SCI) is a debilitating condition that results in significant impairment of motor function and sensation. Despite the ongoing efforts to develop effective treatments, there are currently very limited options available for patients with SCI. Celastrol, natural anti-inflammatory compound extracted from Tripterygium wilfordii, has been shown exhibit anti-apoptotic properties. In this study, we aimed explore therapeutic potential celastrol SCI elucidate underlying molecular mechanisms involved. We found local tissue often experiences decrease cAMP content occurrs apoptosis after However, treatment could promote production by up-regulating VIP-ADCYAP1R1-GNAS pathway. This effectively inhibit phosphorylation JNK prevent apoptosis, ultimately improving exercise ability Together, our reveal may be promising agent

Language: Английский

---

Recent advances and current limitations of available technology to optically manipulate and observe cardiac electrophysiology

Pflügers Archiv - European Journal of Physiology, Journal Year: 2023, Volume and Issue: 475(11), P. 1357 - 1366

Published: Sept. 28, 2023

Abstract Optogenetics, utilising light-reactive proteins to manipulate tissue activity, are a relatively novel approach in the field of cardiac electrophysiology. We here provide an overview light-activated transmembrane channels (optogenetic actuators) currently applied strategies modulate as well newly developed variants yet be implemented heart. In addition, we touch upon genetically encoded indicators sensors) and fluorescent dyes monitor including potential ion homeostasis. The combination two allows for all-optical approaches heart without any physical contact. However, spectral congestion poses major obstacle, arising due overlap excitation/activation emission spectra various optogenetic and/or dyes, resulting optical crosstalk. Therefore, should carefully selected avoid crosstalk consequent disruptions readouts cellular activity. present simultaneously cytosolic calcium, while also performing manipulation. For this, used voltage-sensitive dye ElectroFluor 730p calcium indicator X-Rhod-1 mouse hearts expressing channelrhodopsin-2 (ChR2). By exploiting isosbestic point avoiding ChR2 activation spectrum, introduce imaging manipulation with minimal Future developments both will allow additional more optimised strategies, promising bright future

Language: Английский

---

Rodents’ visual gamma as a biomarker of pathological neural conditions

The Journal of Physiology, Journal Year: 2024, Volume and Issue: 602(6), P. 1017 - 1048

Published: Feb. 19, 2024

Abstract Neural gamma oscillations (indicatively 30–100 Hz) are ubiquitous: they associated with a broad range of functions in multiple cortical areas and across many animal species. Experimental computational works established rhythms as global emergent property neuronal networks generated by the balanced coordinated interaction excitation inhibition. Coherently, activity is strongly influenced alterations synaptic dynamics which often pathological neural dysfunctions. We argue therefore that these an optimal biomarker for probing mechanism Gamma also highly sensitive to external stimuli sensory cortices, especially primary visual cortex (V1), where stimulus dependence has been thoroughly investigated. manipulation tuning particularly easy rodents, have become standard model investigating effects network on oscillations. Overall, rodents’ offers accessible probe dysfunctional information processing conditions. Beyond vision‐related dysfunctions, rodents were indeed reported deficits such migraine, epilepsy neurodegenerative or neuropsychiatric conditions Alzheimer's, schizophrenia autism spectrum disorders. Altogether, connections between physio‐pathological rodent models underscore potential markers (dys)functioning. image

Language: Английский

---