Activation of STING signaling aggravates chronic alcohol exposure-induced cognitive impairment by increasing neuroinflammation and mitochondrial apoptosis.

Aims: Chronic alcohol exposure leads to persistent neurological disorders, which are mainly attributed to neuroinflammation and apoptosis. Stimulator of IFN genes (STING) is essential in the cytosolic DNA sensing pathway and is involved in inflammation and cellular death processes. This study was to examine the expression pattern and biological functions of STING signaling in alcohol use disorder (AUD).

Hypochlorous acid derived from microglial myeloperoxidase could mediate high-mobility group box 1 release from neurons to amplify brain damage in cerebral ischemia-reperfusion injury.

Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia-reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet.

[Grain yield estimation of wheat-maize rotation cultivated land based on Sentinel-2 multi-spectral image: A case study in Caoxian County, Shandong, China].

Establishing the remote sensing yield estimation model of wheat-maize rotation cultivated land can timely and accurately estimate the comprehensive grain yield. Taking the winter wheat-summer maize rotation cultivated land in Caoxian County, Shandong Province, as test object, using the Sentinel-2 images from 2018 to 2019, we compared the time-series feature classification based on QGIS platform and support vector machine algorithm to select the best method and extract sowing area of wheat-maize rotation cultivated land. Based on the correlation between wheat and maize vegetation index and the statistical yield, we screened the sensitive vegetation indices and their growth period, and obtained the vegetation index integral value of the sensitive spectral period by using the Newton-trapezoid integration method.

NRF2 activation suppresses motor neuron ferroptosis induced by the SOD1 mutation and exerts neuroprotection in amyotrophic lateral sclerosis.

The progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS) is caused by a decline in motor neuron function, resulting in worsened motor impairments, malnutrition, respiratory failure and mortality, and there is a lack of effective clinical treatments. The exact mechanism of motor neuronal degeneration remains unclear. Previously, we reported that ferroptosis, which is characterized by the accumulation of lipid peroxide and glutathione depletion in an iron-dependent manner, contributed to motor neuronal death in ALS cell models with the hSOD1 (human Cu/Zn-superoxide dismutase) gene mutation.

CB2R activation ameliorates late adolescent chronic alcohol exposure-induced anxiety-like behaviors during withdrawal by preventing morphological changes and suppressing NLRP3 inflammasome activation in prefrontal cortex microglia in mice.

Background: Chronic alcohol exposure (CAE) during late adolescence increases the risk of anxiety development. Alcohol-induced prefrontal cortex (PFC) microglial activation, characterized by morphological changes and increased associations with neurons, plays a critical role in the pathogenesis of anxiety. Alcohol exposure increases NLRP3 inflammasome expression, increasing cytokine secretion by activated microglia.

Transmission of NLRP3-IL-1β Signals in Cerebral Ischemia and Reperfusion Injury: from Microglia to Adjacent Neuron and Endothelial Cells via IL-1β/IL-1R1/TRAF6.

The pyrin domain-containing protein 3 (NLRP3) inflammasome drives the profound cerebral ischemia and reperfusion injury (I/R) and mediates the secretion of IL-1β (interleukin-1β), which exerts a subsequent cascade of inflammatory injury. The NLRP3-activated-microglial manipulation in adjacent neuronal and endothelial NLRP3 activation has been confirmed in our previous studies. In the present study, we extended the cognition of how microglia mediated neuronal and endothelial NLRP3-IL-1β signaling during cerebral ischemia and reperfusion injury.

Male mice exposed to chronic intermittent ethanol exposure exhibit significant upregulation or downregulation of circular RNAs.

: Circular RNAs (circRNAs) have been crucially implicated in various diseases, however, their involvement in chronic intermittent ethanol (CIE) exposure remains unclear.: The present study was conducted to evaluate the circular RNA expression alteration in brain samples and to identify the molecular mechanisms underlying chronic intermittent ethanol exposure.: Male C57BL/6J mice (10 for each group) were given 4 weeks of chronic intermittent ethanol exposure.

Morphine-induced microglial immunosuppression via activation of insufficient mitophagy regulated by NLRX1.

Background: Chronic morphine exposure induces immunosuppression in the peripheral and central nervous system, resulting in susceptibility of patients to invading pathogens. Mitophagy is a crucial regulator of inflammation, and dysregulated mitophagy may cause immunosuppression, but whether mitophagy is linked with morphine-induced immunosuppression in the brain remains unknown. NLRX1 is the only mitochondrially localized NOD family receptor protein which serves as a critical regulator in immunity and mitophagy activation, but it remains an enigma how NLRX1 functions in the crosstalk between microglial inflammatory defense and mitophagy in the presence of morphine.

Decreased RNA mA methylation enhances the process of the epithelial mesenchymal transition and vasculogenic mimicry in glioblastoma.

RNA N-methyladenosine (mA) modification is gradually thought to be an active participant in the considerable biological processes of glioblastoma (GB), providing us with a novel insight for exploring this disease. However, the role of RNA mA modification during the epithelial mesenchymal transition (EMT) or vasculogenic mimicry (VM) progression has not been investigated in GB. Here we performed a research to validate the impact exerted by AlkB homolog 5 (ALKBH5), one of "erasers" for RNA mA and methyltransferase-like 3 (METTL3) which adds mA modification to the RNAs on the progression of EMT and VM in GB.

MPO/HOCl Facilitates Apoptosis and Ferroptosis in the SOD1 Motor Neuron of Amyotrophic Lateral Sclerosis.

Background: Oxidative stress and reactive oxygen species (ROS) are important in the pathogenesis of amyotrophic lateral sclerosis (ALS). Hypochlorous acid (HOCl) is a powerful oxidant of the reactive oxygen species (ROS) family. HOCl's role in the progress of ALS remains unclear due to the lack of an effective HOCl detection method.

Idebenone attenuates cerebral inflammatory injury in ischemia and reperfusion via dampening NLRP3 inflammasome activity.

Background: Idebenone is a well-appreciated mitochondrial protectant while the mechanisms underlying the neuroprotection in cerebral ischemia and reperfusion (I/R) remain elusive. It has been manifested NLRP3 inflammasom activation contributed to I/R induced damage. It raises questions how exactly NLRP3 inflammasom was activated in microglia and neuron and whether idebenone reverses the process in I/R.

Effect of alteplase versus aspirin plus clopidogrel in acute minor stroke.

The optimal treatment for acute ischemic stroke with mild neurologic deficits is unclear. We aimed to compare the efficacy and safety of alteplase versus dual-antiplatelet therapy in acute minor stroke. We performed a retrospective cohort study of patients with minor ischemic stroke and National Institutes of Health Stroke Scale scores ≤5 presenting within 24 h from last seen normal.

Reperfusion therapy for minor stroke: A systematic review and meta-analysis.

Objectives: Approximately, half of the acute stroke patients with minor symptoms were excluded from thrombolysis in some randomized controlled trials (RCTs). There is little evidence on treating minor strokes with rt-PA. Here, we performed a systematic review and meta-analysis to assess the safety and efficacy of thrombolysis in these patients.

CircRNA expression profiles and function prediction in peripheral blood mononuclear cells of patients with acute ischemic stroke.

Most circular RNAs (circRNAs) belong to a novel class of noncoding RNAs that are produced by back-splicing reactions, and they regulate physiological and pathophysiological processes in human disease. Although circRNA expression has been shown to be altered in the ischemic cerebral tissue in animal studies, the expression profile of circRNA in the patients with acute ischemic stroke (AIS) has not been investigated to date. In this investigation, high-throughput sequencing was carried out to compare the circRNA expression of peripheral blood mononuclear cells (PBMCs) from five patients with AIS and five healthy subjects.

Safety and Feasibility of Repeated Intrathecal Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells in Patients with Neurological Diseases.

Mesenchymal stromal cells (MSCs) have become the most commonly used adult stem cells in regenerative medicine. Preclinical studies have shown that MSCs-based therapy is a potential new treatment approach for neurological diseases. Intrathecal injection has unique feature which allows stem cells to directly migrate to the lesion site in patients with central nervous system (CNS) diseases.

Autophagy alleviates ethanol-induced memory impairment in association with anti-apoptotic and anti-inflammatory pathways.

Chronic excessive drinking leads to a wide spectrum of neurological disorders, including cognitive deficits, such as learning and memory impairment. However, the neurobiological mechanisms underlying these deleterious changes are still poorly understood. We conducted a comprehensive study to investigate the role and mechanism of autophagy in alcohol-induced memory impairment.

Mitochondrial dysfunction induces NLRP3 inflammasome activation during cerebral ischemia/reperfusion injury.

Background: Nod-like receptor protein 3 (NLRP3) inflammasome is a crucial factor in mediating inflammatory responses after cerebral ischemia/reperfusion (I/R), but the cellular location of NLRP3 inflammasome in cerebral I/R has yet come to a conclusion, and there is still no specific evidence to state the relationship between mitochondria and the NLRP3 inflammasome in cerebral I/R.

Methods: In the present study, we detected the cellular localization of NLRP3 inflammasomes in a transient middle cerebral artery occlusion (tMCAO) rat model and a transwell co-culture cell system under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Then, we investigated the relationship between mitochondrial dysfunction and the activation of NLRP3 inflammasomes in different cell types after OGD/R and cerebral I/R injury.

Intrathecal Injection of Allogenic Bone Marrow-Derived Mesenchymal Stromal Cells in Treatment of Patients with Severe Ischemic Stroke: Study Protocol for a Randomized Controlled Observer-Blinded Trial.

Mesenchymal stromal cells (MSCs) can differentiate into multiple tissues. Preclinical studies have shown that MSC-based therapy is a potential new treatment approach for ischemic stroke. These results support the urgent need for further studies of MSC transplantation in the treatment of ischemic stroke in humans.

Hydroxysafflor Yellow A Reprograms TLR9 Signalling Pathway in Ischaemic Cortex after Cerebral Ischaemia and Reperfusion.

Background And Objective: Hydroxysafflor yellow A (HSYA) was reported to suppress inflammation in ischaemic microglia. However, the mechanism through which HSYA inhibits inflammation caused by cerebral ischaemia and reperfusion injury remains unknown. Here, we have mimicked acute cerebral ischaemia and reperfusion injury by subjecting male Sprague-Dawley rats to transient middle cerebral artery occlusion for 90 minutes and have demonstrated that toll-like receptor 9 (TLR9) was upregulated from day 3 after reperfusion, accompanied by the persistent activation of the pro-inflammatory nuclear factor-κB (NF-κB) pathway from 6 hours to day 7.

Mangiferin antagonizes TNF-α-mediated inflammatory reaction and protects against dermatitis in a mice model.

This study aimed to investigate whether mangiferin played a protective role in a well-established dermatitis mouse model and tumor necrosis factor alpha (TNF-α)-induced RAW264.7 macrophages. Contact dermatitis is an inflammatory skin disease in the clinic, while its underlying mechanism still remains to be elucidated.

The TLR9 Antagonist iCpG-ODN at Different Dosages Inhibits Cerebral Ischemia/Reperfusion Injury in Mice.

Background: Inflammatory responses are important mechanisms that are involved in cerebral ischemia/reperfusion(I/R) injury. Whether toll-like receptor 9(TLR9), which belongs to the innate immune system, takes part in the inflammatory responses following cerebral I/R remains unclear.

Method: This study examined the effect of different dosages of the TLR9 antagonist inhibitory oligodeoxynucleotide (iCpG-ODN) on cerebral I/R injury by using a mouse model of transient middle cerebral artery occlusion.

Toll-Like Receptor 3 and Interferon β mRNA Expressions Were Increased in Peripheral Blood of Ischemic Stroke Patients with Good Outcome.

Background: Innate immunity plays an important role in brain ischemic injury, but there are only few studies on the effects of toll-like receptors (TLRs) on cerebral infarction patients up to now. We aimed to evaluate the TLR mRNA expression of patients with different outcomes.

Methods: Eighty-six cases suffering from cerebral infarction within 14 days were assigned into the good outcome group (n = 47) and the bad outcome group (n = 39) depending on the modified Rankin Scale scores (mRS ≤2 at 90 days following stroke onset was good outcome).

Chronic Calcium Channel Inhibitor Verapamil Antagonizes TNF-α-Mediated Inflammatory Reaction and Protects Against Inflammatory Arthritis in Mice.

It is well established that the tumor necrosis factor-α (TNF-α) plays a dominant role in rheumatoid arthritis (RA). Calcium channel is recently reported to be closely associated with various inflammatory diseases. However, whether chronic calcium channel blocker verapamil plays a role in RA still remains unknown.

Activating Autophagy in Hippocampal Cells Alleviates the Morphine-Induced Memory Impairment.

Morphine abuse in treating severe and chronic pain has become a worldwide problem. But, chronic morphine exposure can cause memory impairment with its mechanisms not fully elucidated by past research sstudies which all focused on the harmful effects of morphine. Autophagy is an important pathway for cells to maintain survival.