Rigorous coupled-wave analysis of unilateral Smith-Purcell radiation from asymmetric resonators.

The Smith-Purcell radiation produced by electrons moving closely to a grating can be enhanced by resonances. Here, we show a method to manipulate the directionality of the resonance-enhanced radiation. Using the rigorous coupled-wave analysis method, we compare the radiation from symmetric and asymmetric gratings, showing that the enhanced Smith-Purcell radiation can become unilateral with a perturbation that breaks the structural symmetry. Our work provides an effective method for frequency-domain calculation of Smith-Purcell radiation and also an approach to realize more efficient use of the radiation.

Comparative transcriptome analysis explored the molecular mechanisms of a luxR-type regulator regulating intracellular survival of Aeromonas hydrophila.

Aeromonas hydrophila is not a traditional intracellular bacterium. However, previous studies revealed that pathogenic A. hydrophila B11 could temporarily survive for at least 24 h in fish phagocytes, and the regulation of intracellular survival in bacteria was associated with regulators of the LuxR-type. The mechanisms of luxR08110 on the A. hydrophila's survival in macrophages were investigated using comprehensive transcriptome analysis and biological phenotype analysis in this study. The results showed that after luxR08110 was silenced, the intracellular survival ability of bacteria was significantly diminished. Comparative transcriptome analysis revealed that luxR08110 was a critical regulator of A. hydrophila, which regulated the expression of over 1200 genes, involving in bacterial flagellar assembly and chemotaxis, ribosome, sulphur metabolism, glycerolipid metabolism, and other mechanisms. Further studies confirmed that after the inhibition of expression of luxR08110, the motility, chemotaxis and adhesion of A. hydrophila significantly decreased. Moreover, compared with the wild-type strain, the survival rates of silencing strain were all considerably reduced under both H2O2 and low pH stress conditions. According to both transcriptome analysis and phenotypic tests, the luxR08110 of A. hydrophila could act as global regulator in bacteria intracellular survival. This regulator regulated intracellular survival of A. hydrophila mainly through two ways. One way is to regulate bacterial flagellar synthesis and further affects the motility, chemotaxis and adhesion of bacteria. The other way is to regulate sulphur and glycerolipid metabolisms, thus affecting bacterial energy production and the ability to resist environmental stress.

[Factors influencing the efficacy of initial adrenocorticotropic hormone therapy for infantile epileptic spasms syndrome]. / é¦–æ¬¡ä¿ƒè‚¾ä¸Šè ºçš®è´¨æ¿€ç´ æ²»ç–—å©´å„¿ç™«ç—«ç—‰æŒ›ç»¼åˆå¾ç–—æ•ˆçš„å½±å“å› ç´ åˆ†æž.

OBJECTIVES: To study the factors influencing the short-term (28 days) efficacy of initial adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasms syndrome (IESS), as well as the factors influencing recurrence and prognosis. METHODS: The clinical data were collected from the children with IESS who received ACTH therapy for the first time in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from April 2008 to January 2018 and were followed up for ≥2 years. The multivariate logistic regression analysis was used to evaluate the factors influencing the short-term efficacy of ACTH therapy, recurrence, and long-term prognosis. RESULTS: ACTH therapy achieved a control rate of seizures of 55.5% (111/200) on day 28 of treatment. Of the 111 children, 75 (67.6%) had no recurrence of seizures within 12 months of follow-up. The possibility of seizure control on day 28 of ACTH therapy in the children without focal seizures was 2.463 times that in those with focal seizures (P<0.05). The possibility of seizure control on day 28 of ACTH therapy in the children without hypsarrhythmia on electroencephalography on day 14 of ACTH therapy was 2.415 times that in those with hypsarrhythmia (P<0.05). The possibility of recurrence within 12 months after treatment was increased by 11.8% for every 1-month increase in the course of the disease (P<0.05). The possibility of moderate or severe developmental retardation or death in the children without seizure control after 28 days of ACTH therapy was 8.314 times that in those with seizure control (P<0.05). The possibility of moderate or severe developmental retardation or death in the children with structural etiology was 14.448 times that in those with unknown etiology (P<0.05). CONCLUSIONS: Presence or absence of focal seizures and whether hypsarrhythmia disappears after 14 days of treatment can be used as predictors for the short-term efficacy of ACTH therapy, while the course of disease before treatment can be used as the predictor for recurrence after seizure control by ACTH therapy. The prognosis of IESS children is associated with etiology, and early control of seizures after ACTH therapy can improve long-term prognosis.

A novel homozygous missense mutation in the FASTKD2 gene leads to Lennox-Gastaut syndrome.

FASTKD2 encodes an RNA-binding protein, which is a key post-transcriptional regulator of mitochondrial gene expression. Mutations in FASTKD2 have recently been found in mitochondrial encephalomyopathy, which is characterized by a deficiency in mitochondrial function. To date, seven patients have been reported. Six patients were identified with nonsense or frameshift mutations in the FASTKD2 gene, and only one patient harbored a missense mutation and a nonsense mutation. Here, we identified a novel FASTKD2 homozygous mutation, c.911 T > C, in a patient diagnosed with Lennox-Gastaut syndrome. We observed that the expression of FASTKD2 and the levels of mitochondrial 16 S rRNA were lower in the patient than in the unaffected controls. In conclusion, the missense mutation c.911 T > C caused loss of function in FASTKD2, which was associated with a new phenotype, Lennox-Gastaut syndrome.

Enhancement of Smith-Purcell radiation from cylindrical gratings by quasi-bound states in the continuum.

Smith-Purcell radiation (SPR) is an important means of generating terahertz waves, and the enhancement of SPR is an attractive topic nowadays. Inspired by the phenomenon of special SPR, where the enhancement is achieved by using a high-duty-cycle grating, we describe a new, to the best of our knowledge, but more effective approach to this challenging problem. By deriving a simple analytical solution for the SPR from an annular electron beam passing through a cylindrical metallic grating, we show that the inverse structure, a low-duty-cycle grating can exhibit rather high SPR efficiencies in the presence of quasi-bound states in the continuum (quasi-BICs). The analytical prediction is supported by particle-in-cell simulations, which show that the quasi-BICs can enhance the superradiant SPR generated by a train of electron bunches by orders of magnitude. These results present an interesting mechanism for enhancing the SPR from metallic gratings, and may find applications in terahertz free-electron lasers.

[Recurrence factors for myelin oligodendrocyte glycoprotein antibody disease in children and the effect of recurrence prevention regimens].

OBJECTIVE: To study the clinical features and recurrence factors of myelin oligodendrocyte glycoprotein (MOG) antibody disease in children and the effect of recurrence prevention regimens. METHODS: A retrospective analysis was performed on the medical data of 41 children with MOG antibody disease who were hospitalized in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from December 2014 to September 2020. According to the presence or absence of recurrence, they were divided into a monophasic course group (n=19) and a recurrence group (n=22). According to whether preventive treatment for recurrence was given, the children with recurrence were further divided into a preventive treatment group and a non-preventive treatment group. The clinical features were analyzed for all groups, and the annualized relapse rate (ARR) was compared before and after treatment with prevention regimens. RESULTS: For these 41 children, acute disseminated encephalomyelitis was the most common initial manifestation and was observed in 23 children (56%). Of the 41 children, 22 (54%) experienced recurrence, with 57 recurrence events in total, among which optic neuritis was the most common event (17/57, 30%). The proportion of children in the recurrence group who were treated with corticosteroids for less than 3 months in the acute phase was higher than that in the monophasic course group (64% vs 32%; P < 0.05). There was no significant difference in the ARR between the preventive treatment and non-preventive treatment groups (P > 0.05). The assessment of preventive treatment regimens for 32 cases showed that the children treated with rituximab or azathioprine had a significant reduction in the ARR during treatment (P < 0.05). CONCLUSIONS: More than half of the children with MOG antibody disease may experience recurrence. Most children with recurrence are treated with corticosteroids for less than 3 months in the acute phase. Rituximab and azathioprine may reduce the risk of recurrence.

Role of LuxR-type regulators in fish pathogenic Aeromonas hydrophila.

LuxR-type transcriptional factors are essential in many bacterial physiological processes. However, there have been no reports on their roles in Aeromonas hydrophila. In this study, six stable silent strains were constructed using shRNA. Significant decreases in the expression levels of luxR05 , luxR08 , luxR19 , luxR11 , luxR164 and luxR165 were shown in their respective strains by qRT-PCR. The luxR05 -RNAi and luxR164 -RNAi exhibit the most significant changes in sensitivity to kanamycin and gentamicin. The luxR05 -RNAi showed minimum biofilm formation and the least motility, while luxR164 -RNAi showed minimum biofilm formation, adhesion, growth and extracellular protease activity compared to the wild-type strain. In summary, the results of this paper suggest that all six luxR genes are involved in multiple physiological processes in A. hydrophila and that the roles of luxR05 and luxR164 are highly significant. The sensitivity of luxR05 -RNAi and luxR164 -RNAi to drugs may be closely related to biofilm formation. The luxR05 may play an important role in the pathogenicity of A. hydrophila by regulating the movement, adhesion and biofilm formation of bacteria, whereas luxR164 may be involved in similar functions by regulating bacterial adhesion, extracellular enzyme activity and growth. These results help further our understanding of the drug resistance and pathogenesis of A. hydrophila.

The role of sodA and sodB in Aeromonas hydrophila resisting oxidative damage to survive in fish macrophages and escape for further infection.

Several bacteria have been defined as extracellular pathogens; however, in recent years, it has been confirmed that they have the ability to survive and escape the attack of host phagocytes, thus causing further infection. Previous studies have shown that Aeromonas hydrophila could survive in fish macrophages; however, the mechanism remains unknown. In this study, sodA and sodB of the strain A. hydrophila B11 were stable silenced by shRNA. The survival rates of intracellular sodA-RNAi and sodB-RNAi decreased by 91.8% and 74.9% and the immune escape rates decreased by about 32% and 92% respectively. At the same time, reactive oxygen species (ROS) in fish macrophages that phagocytosed sodA-RNAi and sodB-RNAi increased by 40% and 32.6%, respectively, compared to those of macrophages that phagocytosed the wild-type strain. Compared to sodA, the expression of sodB predominates in A. hydrophila without oxidative stress; however, when exposed to oxidative stress, the magnitude of up-regulation of sodA expression is significantly higher than that of sodB. With increased of methyl viologen concentration, the survival rates of sodA-RNAi and sodB-RNAi were significantly decreased. The expressions of sodA and sodB did not affect the growth of A. hydrophila without oxidative stress, but the inhibition of sodA and sodB expression led to a slight decrease in bacterial growth under oxidative stress. These results indicated that (1) sodA and sodB play an important role in the process of bacterial resistance to ROS damage in host phagocytic cells, allowing them to survive or even escape fish macrophages; (2) the sodB expression was dominant in A. hydrophila without oxidative stress, the sodA expression was up-regulated more significantly under oxidative stress, and sodA and sodB contributed equally to the process of bacterial resistance to ROS; (3) sodA and sodB complement each other and cooperate in the process of intracellular survival of bacteria to protect against ROS damage.

The role and mechanism of icmF in Aeromonas hydrophila survival in fish macrophages.

Survival in host macrophages is an effective strategy for pathogenic bacteria to spread. Aeromonas hydrophila has been found to survive in fish macrophages, but the mechanisms remain unknown. In this paper, the roles and possible mechanisms of IcmF in bacterial survival in fish macrophages were investigated. First, a stable silencing strain icmF-RNAi was constructed by shRNA and RT-qPCR confirmed the expression of icmF was down-regulated by 94.42%. The expression of Hcp, DotU and VgrG was also decreased in icmF-RNAi. The intracellular survival rate of the wild-type strain was 92.3%, while the survival rate of icmF-RNAi was only 20.58%. The escape rate of the wild-type strain was 20%, while that of the icmF-RNAi was only 7.5%. Further studies indicated that the expression of icmF can significantly affect the adhesion, biofilm formation, motility and acid resistance of A. hydrophila, but has no significant effect on the growth of A. hydrophila even under the stress of H2 O2 . The results indicated that IcmF of A. hydrophila not only acts as a structural protein which participates in virulence-related characteristics such as bacterial motility, adhesion and biofilm formation, but also acts as a key functional protein which participates in the interaction between bacteria and host macrophages.

ST2/IL-33-Dependent Microglial Response Limits Acute Ischemic Brain Injury.

ST2, a member of the interleukin (IL) 1 receptor family, and its ligand IL-33 play critical roles in immune regulation and inflammatory responses. This study explores the roles of endogenous IL-33/ST2 signaling in ischemic brain injury and elucidates the underlying mechanisms of action. The expression of IL-33 rapidly increased in oligodendrocytes and astrocytes after 60 min transient middle cerebral artery occlusion (tMCAO). ST2 receptor deficiency exacerbated brain infarction 3 d after tMCAO as well as distal permanent MCAO. ST2 deficiency also aggravated neurological deficits up to 7 d after tMCAO. Conversely, intracerebroventricular infusions of IL-33 after tMCAO attenuated brain infarction. Flow cytometry analyses demonstrated high levels of ST2 expression on microglia, and this expression was dramatically enhanced after tMCAO. The absence of ST2 enhanced the expression of M1 polarization markers on microglia/macrophages, and impaired the expression of M2 polarization markers after tMCAO. In vitro studies on various types of cultures and coculture systems confirmed that IL-33/ST2 signaling potentiated expression of IL-10 and other M2 genes in primary microglia. The activation of ST2 on microglia led to a protective phenotype that enhanced neuronal survival against oxygen glucose deprivation. Further in vitro studies revealed that IL-33-activated microglia released IL-10, and that this was critical for their neuroprotective effects. Similarly, intracerebroventricular infusions of IL-33 into IL-10 knock-out mice failed to provide neuroprotection against tMCAO in vivo These results shed new light on the IL-33/ST2 axis as an immune regulatory mechanism that serves as a natural brake on the progression of ischemic brain injury.SIGNIFICANCE STATEMENT This is the first study to identify the function of interleukin (IL) 33/ST2 signaling in poststroke microglial responses and neuroprotection against ischemia. Using two models of ischemic stroke, we demonstrate here that ST2 deficiency shifted microglia/macrophages toward a M1-like phenotype, thereby expanding brain infarcts and exacerbating long-term behavioral deficits after stroke. Using stroke models and various in vitro culture and coculture systems, we further characterized a previously undefined mechanism whereby IL-33/ST2 engagement stimulates the production of IL-10 from microglia, which, in turn, enhances neuronal survival upon ischemic challenge. These results shed light on endogenous IL-33/ST2 signaling as a potential immune regulatory mechanism that serves to promote beneficial microglial responses and mitigate ischemic brain injury after stroke.

Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic studies demonstrated that regulatory T cells completely abolished the tPA-induced elevation of MMP9 and CCL2 after stroke. Using MMP9 and CCL2 knockout mice, we discovered that both molecules partially contributed to the protective actions of regulatory T cells. In an in vitro endothelial cell-based model of the blood-brain barrier, we confirmed that regulatory T cells inhibited tPA-induced endothelial expression of CCL2 and preserved blood-brain barrier integrity after an ischaemic challenge. Lentivirus-mediated CCL2 knockdown in endothelial cells completely abolished the blood-brain barrier protective effect of regulatory T cells in vitro. Altogether, our studies suggest that regulatory T cell adoptive transfer may alleviate thrombolytic treatment-induced haemorrhage in stroke victims. Furthermore, regulatory T cell-afforded protection in the tPA-treated stroke model is mediated by two inhibitory mechanisms involving CCL2 and MMP9. Thus, regulatory T cell adoptive transfer may be useful as a cell-based therapy to improve the efficacy and safety of thrombolytic treatment for ischaemic stroke.

Adoptive Regulatory T-cell Therapy Attenuates Perihematomal Inflammation in a Mouse Model of Experimental Intracerebral Hemorrhage.

The CD4+CD25+ regulatory T cells (Tregs), an innate immunomodulator, suppress cerebral inflammation and maintain immune homeostasis in multiple central nervous system injury, but its role in intracerebral hemorrhage (ICH) has not been fully characterized. This study investigated the effect of Tregs on brain injury using the mouse ICH model, which is established by autologous blood infusion. The results showed that tail intravenous injection of Tregs significantly reduced brain water content and Evans blue dye extravasation of perihematoma at day (1, 3 and 7), and improved short- and long-term neurological deficits following ICH in mouse model. Tregs treatment reduced the content of pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and malondialdehyde, while increasing the superoxide dismutase (SOD) enzymatic activity at day (1, 3 and 7) following ICH. Furthermore, Tregs treatment obviously reduced the number of NF-κB+, IL-6+, TUNEL+ and active caspase-3+ cells at day 3 after ICH. These results indicate that adoptive transfer of Tregs may provide neuroprotection following ICH in mouse models.

Enhanced Neuroprotection of Minimally Invasive Surgery Joint Local Cooling Lavage against ICH-induced Inflammation Injury and Apoptosis in Rats.

Hypothermia treatment is one of the neuroprotective strategies that improve neurological outcomes effectively after brain damage. Minimally invasive surgery (MIS) has been an important treatment of intracerebral hemorrhage (ICH). Herein, we evaluated the neuroprotective effect and mechanism of MIS joint local cooling lavage (LCL) treatment on ICH via detecting the inflammatory responses, oxidative injury, and neuronal apoptosis around the hematoma cavity in rats. ICH model was established by type IV collagenase caudatum infusion. The rats were treated with MIS 6 h after injection, and then were lavaged by normothermic (37 °C) and hypothermic (33 °C) normal saline in brain separately. The results indicated that MIS joint LCL treatment showed enhanced therapeutic effects against ICH-induced inflammation injury and apoptosis in rats, as convinced by the decline of TUNEL-positive cells, followed by the decrease of IL-1ß and LDH and increase of IL-10 and SOD. This study demonstrated that the strategy of using MIS joint LCL may achieve enhanced neuroprotection against ICH-induced inflammation injury and apoptosis in rats with potential clinic application.

Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1.

Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies.

Rosiglitazone Promotes White Matter Integrity and Long-Term Functional Recovery After Focal Cerebral Ischemia.

BACKGROUND AND PURPOSE: Oligodendrogenesis is essential for white matter repair after stroke. Although agonists of peroxisome proliferator-activated receptors γ confer neuroprotection in models of cerebral ischemia, it is not known whether this effect extends to white matter protection. This study tested the hypothesis that the peroxisome proliferator-activated receptors γ agonist rosiglitazone enhances oligodendrogenesis and improves long-term white matter integrity after ischemia/reperfusion. METHODS: Male adult C57/BL6 mice (25-30 g) were subjected to 60-minute middle cerebral artery occlusion and reperfusion. Rosiglitazone (3 mg/kg) was injected intraperitoneally once daily for 14 days beginning 2 hours after reperfusion. Sensorimotor and cognitive functions were evaluated ≤21 days after middle cerebral artery occlusion. Immunostaining was used to assess infarct volume, myelin loss, and microglial activation. Bromodeoxyuridine (BrdU) was injected for measurements of proliferating NG2(+) oligodendrocyte precursor cells (OPCs) and newly generated adenomatous polyposis coli(+) oligodendrocytes. Mixed glial cultures were used to confirm the effect of rosiglitazone on oligodendrocyte differentiation and microglial polarization. RESULTS: Rosiglitazone significantly reduced brain tissue loss, ameliorated white matter injury, and improved sensorimotor and cognitive functions for at least 21 days after middle cerebral artery occlusion. Rosiglitazone enhanced OPC proliferation and increased the numbers of newly generated mature oligodendrocytes after middle cerebral artery occlusion. Rosiglitazone treatment also reduced the numbers of Iba1(+)/CD16(+) M1 microglia and increased the numbers of Iba1(+)/CD206(+) M2 microglia after stroke. Glial culture experiments confirmed that rosiglitazone promoted oligodendrocyte differentiation, perhaps by promoting microglial M2 polarization. CONCLUSIONS: Rosiglitazone treatment improves long-term white matter integrity after cerebral ischemia, at least, in part, by promoting oligodendrogenesis and facilitating microglial polarization toward the beneficial M2 phenotype.

Attenuation of Cisplatin-Induced Neurotoxicity by Cyanidin, a Natural Inhibitor of ROS-Mediated Apoptosis in PC12 Cells.

Cisplatin-based chemotherapy in clinic is severely limited by its adverse effect, including neurotoxicity. Oxidative damage contributes to cisplatin-induced neurotoxicity, but the mechanism remains unclearly. Cyanidin, a natural flavonoid compound, exhibits powerful antioxidant activity. Hence, we investigated the protective effects of cyanidin on PC12 cells against cisplatin-induced neurotoxicity and explored the underlying mechanisms. The results showed that cisplatin-induced cytotoxicity was completely reversed by cyanidin through inhibition of PC12 cell apoptosis, as proved by the attenuation of Sub-G1 peak, PARP cleavage, and caspases-3 activation. Mechanistically, cyanidin significantly inhibited reactive oxygen species (ROS)-induced DNA damage in cisplatin-treated PC12 cells. Our findings revealed that cyanidin as an apoptotic inhibitor effectively blocked cisplatin-induced neurotoxicity through inhibition of ROS-mediated DNA damage and apoptosis, predicating its therapeutic potential in prevention of chemotherapy-induced neurotoxicity. Cisplatin caused DNA damage, activated p53, and subsequently induced PC12 cells apoptosis by triggering ROS overproduction. However, cyanidin administration effectively inhibited DNA damage, attenuated p53 phosphorylation, and eventually reversed cisplatin-induced PC12 cell apoptosis through inhibition ROS accumulation.

Essential role of program death 1-ligand 1 in regulatory T-cell-afforded protection against blood-brain barrier damage after stroke.

BACKGROUND AND PURPOSE: Our recent research revealed that adoptively transferred regulatory T cells (Tregs) reduced acute ischemic brain injury by inhibiting neutrophil-derived matrix metalloproteinase-9 (MMP-9) and protecting against blood-brain barrier damage. The mechanisms underlying Treg interactions with neutrophils remain elusive. This study evaluates the contribution of program death 1-ligand 1 (PD-L1) to Treg-mediated neutrophil inhibition and neuroprotection after cerebral ischemia. METHODS: In vitro experiments were performed using a transwell system or a coculture system allowing cell-to-cell contact. Focal cerebral ischemia was induced in mice for 60 minutes. Tregs (2×10(6)) isolated from donor animals (wild-type or PD-L1-/-) were intravenously injected into ischemic recipients 2 hours after middle cerebral artery occlusion (MCAO). MMP-9 production, blood-brain barrier permeability, and brain infarct were assessed at 1 or 3 days after MCAO. RESULTS: In vitro experiments reveal that Treg-mediated inhibition of neutrophil MMP-9 required direct cell-to-cell contact. The suppression of MMP-9 was abolished when Tregs were pretreated with PD-L1 neutralizing antibodies or when neutrophils were pretreated with PD-1 antibodies. In vivo studies confirmed that intravenous administration of Tregs pretreated with PD-L1 antibodies or Tregs isolated from PD-L1-deficient mice failed to inhibit MMP-9 production by blood neutrophils 1 day after 60 minutes MCAO. Furthermore, the blood-brain barrier damage after MCAO was greatly ameliorated in PD-L1-competent Treg-treated mice but not in PD-L1-compromised Treg-treated mice. Consequently, PD-L1 dysfunction abolished Treg-mediated brain protection and neurological improvements 3 days after MCAO. CONCLUSIONS: PD-L1 plays an essential role in the neuroprotection afforded by Tregs against cerebral ischemia by mediating the suppressive effect of Tregs on neutrophil-derived MMP-9.

[Analysis of monosaccharide compositions in polysaccharides from exopleura of Ginkgo biloba].

A high-performance liquid chromatography method of pre-column derivatization with 1-phenyl-3-methyl-5 -pyrazolone (PMP) has been established for determination of 6 kinds of monosaccharides simultaneously. A special Agilent HC-C18 column (4. 6 mm x 250 mm, 5 microm), optimized for the separation of PMP derivatives, was used at ambient temperature of 40 degrees C. The PMP derivatives elution was performed with a mixture of 0.1 mol x L(-1) phosphate buffer (pH 6. 8) and acetonitrile in a ratio of 84: 16 at a flow rate of 1 mL x min(-1), and UV absorbance of the effluent was monitored at 245 nm. The results showed that the polysaccharides from exopleura of Ginkgo biloba were acidic heteropolysaccharides mainly containing mannose, rhamnose, D-galacturonic acid, glucose, galactose, arabinose, with the molar ratio of 0.032: 0.14: 0.296: 0.403:0.106: 0.046.

Interleukin-4 Modulates Neuroinflammation by Inducing Phenotypic Transformation of Microglia Following Subarachnoid Hemorrhage.

Neuroinflammation, a key pathological feature following subarachnoid hemorrhage (SAH), can be therapeutically targeted by inhibiting microglia M1 polarization and promoting phenotypic transformation to M2 microglia. Interleukin-4 (IL-4) is a pleiotropic cytokine known to its regulation of physiological functions of the central nervous system (CNS) and mediate neuroinflammatory processes. However, its specific role in neuroinflammation and microglia responses following SAH remains unexplored. In this investigation, we established both in vivo and in vitro SAH models and employed a comprehensive array of assessments, including ELISA, neurofunctional profiling, immunofluorescence staining, qRT-PCR, determination of phagocytic capacity, and RNA-Seq analyses. The findings demonstrate an elevated expression of IL-4 within cerebrospinal fluid (CSF) subsequent to SAH. Furthermore, exogenous administration of IL-4 ameliorates post-SAH neurofunctional deficits, attenuates cellular apoptosis, fosters M2 microglia phenotype conversion, and mitigates neuroinflammatory responses. The RNA-Seq analysis signifies that IL-4 governs the modulation of neuroinflammation in microglia within an in vitro SAH model through intricate cascades of signaling pathways, encompassing interactions between cytokines and cytokine receptors. These discoveries not only augment comprehension of the neuropathogenesis associated with post-SAH neuroinflammation but also present novel therapeutic targets for the management thereof.

LncRNA H19 knockdown promotes neuropathologic and functional recovery via the Nrf2/HO-1 axis after traumatic brain injury.

AIMS: Traumatic brain injury (TBI) stands as a significant concern in public health, frequently leading to enduring neurological deficits. Long non-coding RNA H19 (lncRNA H19) exerts a potential regulator role in the pathology of brain injury. This study investigates the effects of lncRNA H19 knockdown (H19-KD) on the pathophysiology of TBI and its potential neuroprotective mechanisms. METHODS: Controlled cortical impact was employed to establish a stable TBI mouse model. The expression levels of various genes in perilesional cortex and striatum tissue after TBI was detected by RT-qPCR. AAV9-shRNA-H19 was injected into the lateral ventricle of mice to knockdown the expression of lncRNA H19. Various behavioral tests were performed to evaluate sensorimotor and cognitive functions after TBI. Immunofluorescence and Nissl staining were performed to assess brain tissue damage and neuroinflammation. The Nrf2 and HO-1 expression was performed by Western blot. RESULTS: After TBI, the expression of lncRNA H19 was elevated in perilesional tissue and gradually reverted to baseline. Behavioral tests demonstrated that H19-KD significantly promoted the recovery of sensorimotor and cognitive functions after TBI. Besides, H19-KD reduced brain tissue loss, preserved neuronal integrity, and ameliorated white matter damage at the histological level. In addition, H19-KD restrained the pro-inflammatory and facilitated anti-inflammatory phenotypes of microglia/macrophages, attenuating the neuroinflammatory response after TBI. Furthermore, H19-KD promoted activation of the Nrf2/HO-1 axis after TBI, while suppression of Nrf2 partially abolished the neuroprotective effect. CONCLUSION: H19-KD exerts neuroprotective effects after TBI in mice, partially mediated by the activation of the Nrf2/HO-1 axis.