Interleukin-4 promotes microglial polarization toward a neuroprotective phenotype after retinal ischemia/reperfusion injury

Glaucoma results from irreversible loss of retinal ganglion cells(RGCs)through an unclear mechanism.Microglial polarization and neuroinflammation play an important role in retinal degeneration.Our study aimed to explore the function of microglial polarization during glaucoma progression and identify a strategy to alleviate retinal neuroinflammation.Retinal ischemia/reperfusion injury was induced in C57BL/6 mice.In a separate cohort of animals,interleukin(IL)-4(50 ng/mL,2μL per injection)or vehicle was intravitreally injected after retinal ischemia/reperfusion injury.RGC loss was assessed by counting cells that were positive for the RGC marker RNA binding protein,mRNA processing factor in retinal flat mounts.The expression of classically activated(M1)and alternatively activated(M2)microglial markers were assessed by quantitative reverse transcription-polymerase chain reaction,immunofluorescence,and western blotting.The results showed that progressive RGC loss was accompanied by a continuous decrease in M2 microglia during the late phase of the 28-day period after retinal ischemia/reperfusion injury.IL-4 was undetectable in the retina at all time points,and intravitreal IL-4 administration markedly improved M2 microglial marker expression and ameliorated RGC loss in the late phase post-retinal ischemia/reperfusion injury.In summary,we observed that IL-4 treatment maintained a high number of M2 microglia after RIR and promoted RGC survival.

Association between Promoter Polymorphisms of Interleukin-4 Gene and Allergic Rhinitis Risk: a Meta-analysis

Summary： The relationship of interleukin-4 （IL-4） C-33T and C-590T （C-589T） gene polymorphisms with allergic rhinitis was analyzed. Data about the case control studies of IL-4 gene promoter polymorphisms [C-33T and C-590T （C-589T）] and their association with allergic diseases and correlation between serum IL-4 levels and allergic rhinitis were retrieved. The Stata 12.0 statistical soitvcare was applied to analyze the correlation between IL-4 gene polymorphisms and allergic rhinitis. The meta-analysis result of TT/CC genotype of -590 （-589） polymorphism showed a significant association with allergic diseases [OR=1.93, 95% CI （1.61 2.31）, P=0.00]. Meta-analysis of the TT＋TC versus CC genotype of IL-4 C-33/T polymorphism revealed significant associations with allergic diseases [OR=3.23, 95% CI （1.13-9.25）, P=0.03]. Meanwhile, there was a significant correlation between serum IL-4 levels and allergic rhinitis [OR=2.52, 95% CI-（1.80-3.23）, P=0.00]. IL-4 gene -590 TT genotype may increase the risk of allergic rhinitis and the T allele mutation of -33 might be correlated with aller- gic rhinitis.

The Akt/glycogen synthase kinase-3β pathway participates in the neuroprotective effect of interleukin-4 against cerebral ischemia/reperfusion injury

Interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also called protein kinase B, PKB)/glycogen synthase kinase-3β(Akt/GSK-3β) signaling pathway is involved in oxidative stress, the inflammatory response, apoptosis, and autophagy. However, it is not yet clear whether the Akt/GSK-3β pathway participates in the neuroprotective effect of IL-4 against cerebral ischemia/reperfusion injury. In the present study, we established a cerebral ischemia/reperfusion mouse model by middle cerebral artery occlusion for 60 minutes followed by a 24-hour reperfusion. An IL-4/anti-IL-4 complex(10 μg) was intraperitoneally administered 30 minutes before surgery. We found that administration of IL-4 significantly alleviated the neurological deficits, oxidative stress, cell apoptosis, and autophagy and reduced infarct volume of the mice with cerebral ischemia/reperfusion injury 24 hours after reperfusion. Simultaneously, IL-4 activated Akt/GSK-3β signaling pathway. However, an Akt inhibitor LY294002, which was injected at 15 nmol/kg via the tail vein, attenuated the protective effects of IL-4. These findings indicate that IL-4 has a protective effect on cerebral ischemia/reperfusion injury by mitigating oxidative stress, reducing apoptosis, and inhibiting excessive autophagy, and that this mechanism may be related to activation of the Akt/GSK-3β pathway. This animal study was approved by the Animal Ethics Committee of Renmin Hospital of Wuhan University, China(approval No. WDRY2017-K037) on March 9, 2017.

The Relationship between Polymorphisms of Interleukin-4 Gene and Silicosis

Objective To explore the relationship between polymorphisms of interleukin-4 （IL-4） gene （-33, ＋45, intron3, ＋429, ＋448） and the susceptibility of silicosis. Methods A case-control study was carried out. 101 silicosis patients were selected as cases. As strictly matching, 121 of non silicosis workers were selected as the controls. The polymophisms of IL-4 （five locus） were detected by the method of polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） techniques. Results The GA genotype in the IL-4＋429 locus and the CC genotype in the IL-4＋448 locus were found. The frequencies ofAA, GG and AG of IL-4＋45 locus in the cases were 55.4%, 10.9%, and 33.7% and in the controls were 62.0%, 12.6%, and 26.4%. The differences between cases and controls were not significant. The frequencies of B1B1, B2B2, and B1B2 of intron3 VNTR locus in the cases were 73.3%, 1.0%, and 25.7% and in the controls were 68.6%, 1.7%, and 29.8%. The differences were not significant. The frequencies of TT, CC, and CT in -33 locus in the cases were 55.4%, 11.9%, and 32.7% and in the controls were 69.4%, 4.1%, and 26.4%. The differences were significant （P=0.034）. Conclusion The relationship between genetic polymorphism of IL-4-33 site and silicosis has been found and -33TT is a protective genotype for silicosis.

Interleukin-4 affects microglial autophagic flux

Interleukin-4 plays an important protective role in Alzheimer’s disease by regulating microglial phenotype,phagocytosis of amyloid-β,and secretion of anti-inflammatory and neurotrophic cytokines.Recently,increasing evidence has suggested that autophagy regulates innate immunity by affecting M1/M2 polarization of microglia/macrophages.However,the role of interleukin-4 in microglial autophagy is unknown.In view of this,BV2 microglia were treated with 0,10,20 or 50 ng/mL interleukin-4 for 24,48,or 72 hours.Subsequently,light chain 3-II and p62 protein expression levels were detected by western blot assay.BV2 microglia were incubated with interleukin-4(20 ng/mL,experimental group),3-methyladenine(500μM,autophagy inhibitor,negative control group),rapamycin(100 nM,autophagy inductor,positive control group),3-methyladenine+interleukin-4(rescue group),or without treatment for 24 hours,and then exposed to amyloid-β(1μM,model group)or vehicle control(control)for 24 hours.LC3-II and p62 protein expression levels were again detected by western blot assay.In addition,expression levels of multiple markers of M1 and M2 phenotype were assessed by real-time fluorescence quantitative polymerase chain reaction,while intracellular and supernatant amyloid-βprotein levels were measured by enzyme-linked immunosorbent assay.Our results showed that interleukin-4 induced microglial autophagic flux,most significantly at 20 ng/mL for 48 hours.Interleukin-4 pretreated microglia inhibited blockade of amyloid-β-induced autophagic flux,and promoted amyloid-βuptake and degradation partly through autophagic flux,but inhibited switching of amyloid-β-induced M1 phenotype independent on autophagic flux.These results indicate that interleukin-4 pretreated microglia increases uptake and degradation of amyloid-βin a process partly mediated by autophagy,which may play a protective role against Alzheimer’s disease.

Effects of Micronutrients on Oxidative Stress and Islet Function in Type 1 Diabetes Mellitus Rats:Relationships to Th2 Type Cytokines,Interleukin-4,and Interluekin-10

To observe the effects of the micronutrients on oxidative and autoimmune destruction of islets so as to prevent a person from the onset and development of type 1 Diabetes Mellitus （T1DM）, the interleukin-4 and interleukin-10 expressions of lymphocytes in peripheral blood and spleen of T1DM rats were determined by flow cytometry. GSH-Px activity and MDA level in the rats＇ pancreas were measured using biochemical methods. The insulin contents in serum and β cell insulin secret storage were tested by RIA and IHC, respectively. There was an increase in the percentages of IL-4 and IL-10 positive lymphocytes in the peripheral blood and spleen of the groups of rats supplemented with various combinations of micronutrients（p 〈0.01 and p 〈0.05, respectively） ; the blood glucose concentration decreased （p 〈 0. 05 ） ; both the functional β cell in islets and the insulin content in pancreatic tissue increased （p 〈 0. 05 and p 〈0. 01 ） ; the GSH-Px activity and MDA level of pancreas in the rats enhanced and decreased respectively（p 〈0. 01 and p 〈 0. 05）. The results suggest that micronutrients may alleviate the islet lesions by upregulating the expressions of IL-4 and IL-10 and lowering oxidative stress in diabetic rats .

Effect of neuropeptide Y on white matter demyelination and serum interleukin-4 and gamma-interferon levels in the guinea pig with experimental allergic encephalomyelitis

BACKGROUND： Neuropeptide Y （NPY） may influence differentiation of Th cells immunological pathology of experimental allergic encephalomyelitis （EAE） is differentiation of Th cells It is assumed that the related to abnormal OBJECTIVE： To investigate the effect of NPY on white matter demyelination, the serum levels interleukin-4 （IL-4） and gamma-interferon （IFN-γ ）, as well as EAE pathogenesis in an EAE guinea pig model following NPY injection into the lateral cerebral ventricle. DESIGN, TIME AND SETTING： A randomized controlled animal study, which was performed in the Infection Immunity Animal Laboratory, Affiliated Hospital of Luzhou Medical College, China, from October 2005 to April 2006. MATERIALS： Thirty healthy female guinea pigs of 8-12 weeks of age, and 10 healthy female rats of three months of age were used. NPY was provided by Sigma Company, USA. NPY kit was provided by Beijing Huaying Biotechnology Institute, China. METHODS： Thirty guinea pigs were randomly divided into three groups： normal control group, EAE model group, and NPY intervention group （n =10 per group）. Normal control group and EAE model group： Saline （10μ L, once） was injected into the lateral cerebral ventricle. After one week, the same volume of Freund＇s adjuvant complete was either injected subcutaneously into two post-palms or EAE was modeled. NPY intervention group： EAE was modeled after one week and NPY was injected （10 μ L of 6 nmol NPY, once） into the lateral cerebral ventricle. Myelin basic protein （MBP） antigen made from rat spinal cord homogenate and Freund＇s adjuvant complete were injected subcutaneously into both post-palms （0.2 mL per palm） to establish the EAE model. MAIN OUTCOME MEASURES： White matter demyelination of the cerebrum, cerebellum, brain stem, and spinal cord were observed by light microscopy after HE staining. Levels of serum IFN-γ and IL-4 were detected by the double antibody sandwich ABC-ELISA technique. NPY content was detected by radioimmunoassay. RESULTS： Pathological alterations in the NPY intervention groups were reduced compared to those in the EAE model group, suggesting a reduction and remission of white matter demyelination with NPY treatment. When compared to the model group, the serum IL-4 level was increased in the NPY intervention group during the high-frequent EAE stage （P 〈 0.01）, but the serum IFN-γ level was decreased （P 〈 0.01）. Furthermore, the EAE latency was prolonged （P 〈 0.01）, the neurological scores were decreased in the high-frequent EAE stage （P 〈 0.01）, and the death rate was decreased （P 〈 0.05）. NPY content and the serum IL-4 level at the peak stage were positively correlated with those in the latent phase （r =0.863-0.900, P 〈 0.01）, but negatively correlated with neurological scores at the peak stage （r=- -0.068 to -0.863, P 〈 0.05-0.01）. The IFN-γ level at the peak stage was negatively correlated to that in the latent phase （r = -0.683-0.650, P 〈 0.05）, but positively correlated to neurological scores at the peak stage （r =0.975, 0.845, P 〈 0.05）. CONCLUSION： NPY injection into the lateral cerebral ventricle can promote the secretion of IL-4, inhibit the production of IFN-γ, relieve white matter demyelination, and inhibit EAE attack in an experimental model of EAE.

Effects of Intrinsic Nitric Oxide on the Expression of Interleukin-4 and IFN-γ mRNA in the Bronchial and Lung Tissues of Sensitized Rats

Summary: To investigate the effects of intrinsic nitric oxide (NO) on the expression of interleukin-4 (IL-4) mRNA and interferon-γ (IFN-γ) mRNA in the airway inflammation of asthma, the rat models of asthmatic inflammation were established by sensitizing and then challenging the animals with ovalbumin. The 24 animals were randomly divided into control group, sensitized group, sensitized and L-Arg-treated group as well as L-NAME-treated group equally. By using in situ hybridization combined with compute physiological quantitative imaging analysis techniques, the influence of intrinsic NO on the expression of IL-4 mRNA and IFN-Y mRNA in the airway inflammatory cells was observed. In situ hybridization study demonstrated that IL-4 mRNA expres- sion was obviously increased as compared with that in the control group, mainly distributed in the inflammatory cells in the submucous of airways in the sensitized group. The increase of intensity of IL-4 mRNA expression was positively correlated with the numbers of eosinophil (Eos) and lymphocyte (both with P<0. 05) in the sensitized group. There was no statistically difference IFN- γ expression between the control group and the sensitized group. Imaging analysis showed that L- NAME could inhibit the expression of IL-4 mRNA (P<0. 05) and increase the expression of IFNY mRNA (P<0. 05), while L-Arg could increase the expression of IL-4 mRNA in inflammatory cells (P<0. 05). It was indicated that a suitable levels of intrinsic NO can influence the expression of IL-4 mRNA of Th2 lymphocytes and the expression of IFN-γ mRNA of Th1 lymphocytes and in turn, promote the development of asthmatic airway inflammation.

Interactions of thymic stromal lymphopoietin with interleukin-4 in adaptive immunity during Aspergillus fumigatus keratitis

AIM:To investigate the potential interactions of thymic stromal lymphopoietin(TSLP)with interleukin-4(IL-4)in adaptive immunity during fungal keratitis(FK).METHODS:An FK mouse model was induced with Aspergillus fumigatus(AF)hyphal infection.Mice were divided into several groups:untreated,phosphate buffer saline(PBS),infected with AF,and pretreated with a scrambled siRNA,a TSLP-specific siRNA(TSLP siRNA),murine recombinant TSLP(rTSLP),immunoglobulin G(IgG),murine recombinant IFN(rIFN-γ),murine recombinant IL-4(rI L-4),rIL-13,murine recombinant IL-17A(rIL-17A),and murine recombinant IL-17F(rIL-17F)groups.Quantitative realtime reverse transcription-polymerase chain reaction(qRTPCR)and enzyme-linked immunosorbent assay(ELISA)or Western blot were performed to determine mRNA and protein levels in the inflamed cornea.Cytokine locations were observed by immunofluoresence staining after AF hyphal infection.RESULTS:Compared to those in the untreated group,TSLP and T helper type 1(Th1)cytokine levels in the AF group were upregulated at 24 h post infection(hpi),and those of T helper type 2(Th2)and T helper type 17(Th17)cytokines were increased at 5 d post infection(dpi).Th2 cytokine levels were decreased in the TSLP siRNA-pretreated group and increased in the rTSLP-pretreated group compared with the AF group.The TSLP level was increased in the rIL-4-pretreated group,but there were no significant changes among the other groups.Immunofluorescence staining showed cytokine locations after AF hyphal infection.CONCLUSION:TSLP induces a Th2 immune response and promots Th2 T cell differentiation in vivo.IL-4 promotes TSLP secretion.Therefore,TSLP with IL-4 regulates adaptive immunity in FK.

Association between interleukin-4 polymorphisms and asthma

Objective:To perform a systematic review and meta analysis on the association of C-589T and C-590T polymorphisms of IL-4 with asthma and to estimate allele frequencies, the magnitude of the gene effect as well as the possible mode of inheritance. Methods: A genetic model-free approach was used to perform a meta analysis. Heterogeneity, sensitivity analysis and publication bias were also explored. Results: Our meta analysis summarized the evidence to date regarding the association of C-589T and C-590T polymorphisms in the promoter region of IL-4 gene with asthma. For C-590T, the results showed a significant recessive genetic model, and the CC genotype was about 24% less likely to have asthma than the genotype CT and TT. Although there was evidence suggesting a recessive genetic model for C-589T, the recessive model was not statistically significant. Conclusion: This meta analysis suggests that there may be an important effect of single nucleotide polymorphisms (SNPs) in the promoter region of IL-4 gene on the pathogenesis of asthma.

EFFECTS OF INTERLEUKIN-4 ON GRANULOCYTE-MACROPHAGE-COLONY FORMATION FROM MURINE BONE MARROW CELLS AND HEMATOPOIETIC RECONSTITUTION FOLLOWING MURINE ALLOGENEIC BONE MARROW TRANSPLANTATION

We investigated the effects of mouse recombinant IL-4 on hematopoiesis in vitro and in vivo. IL-4 alone was found to be incapable of stimulating colony formation, but it inhibited both IL-3-and GM-CSF-induced colony formation by murine hematopoietic progenitor cells. In contrast, colony formation induced by G-CSF was enhanced in the presence of IL-4. We also studied the influence of IL-4 on hematopoietic reconstiution after allogeneic bone marrow transplantation in a murine medel, and found that IL-4 had significant inhibitory effects on neutrophil recovery and that neutrophil recovery accelerated by IL-3 and G-CSF was significantly suppressed by IL-4. The combination of IL-4 and GM-SF caused a significant decrease in the absolute number of neutrophils.

Effects of Theophylline on Plasma Levels of Interleukin-4,Cyclic Nucleotides and Pulmonary Functions in Patients with Chronic Obstructive Pulmonary Disease

Summary: In order to measure the plasma levels of interleukin 4 (IL 4), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in patients with chronic obstructive pulmonary disease (COPD) and observe the effects of oral theophylline on them, we divided 28 COPD patients into COPD experimental group and COPD control group. Plasma levels of IL 4, cAMP and cGMP as well as parameters of pulmonary function tests were measured in these 2 groups before and after 2 weeks of treatment with oral theophylline (Protheo, 400 mg, qd) or placebo. Plasma levels of IL 4 and cGMP were significantly elevated in patients with COPD as compared with normal controls ( P <0.05), while cAMP and cAMP/cGMP were significantly lower than those in controls ( P <0.01). Plasma level of IL 4 was inversely correlated with forced expiratory volume at the first second (FEV 1) and with maximum expiratory flow rate at 50 % of forced vital capacity (V 50 ) (both r =-0.46, P <0.05) while it was directly correlated with the scores of the clinical manifestations ( r =0.57, P <0.05) in COPD patients. Two weeks after treatment with theophylline, IL 4 and cGMP in COPD experimental group were decreased significantly while cAMP and cAMP/cGMP increased significantly ( P <0.05). The change of IL 4 was inversely correlated with the changes of FEV 1 and V 50 ( r =-0.53 and -0.54, respectively, P <0.05). Two weeks after placebo treatment, the COPD control group did not show such changes. We are led to conclude that IL 4 might play a role in the pathoge nesis of the airway inflammation and air flow limitation in COPD patients and the mechanisms of theophylline's therapeutic effects of attenuating air flow limitation may partially depend on its anti inflammatory effects on the airways which, in turn, is dependent on its inhibitory effects on some inflammatory mediators such as IL 4.

Study on The Role of Interleukin-4 in Experimental Murine Systemic Candidiasis

In order to investigate the role of interleukin 4 in experimental murine systemic Candidiasis, we created the intact and dexamethasone induced immunosuppressed murine systemic Candidiasis models. In these models, two site ELISA and RT PCR were applied to determine the level of IL 4 protein and mRNA expression in spleens respectively, clone forming units of infected kidneys were determined with the plating dilution method, and mean survival time of the mice was recorded. The results showed that, when compared with the controls, protein level of IL 4 increased in both intact mice infected with lethal doses of yeast (day 3, P <0.05; day 7, P <0 001) and immunosuppressed mice infected with sublethal doses of yeast (day 3, P >0.05; day 7, P <0.05). Furthermore, the level of IL 4 was higher on day 7 than on day 3 after infection ( P <0 001 and P <0.05 respectively in two groups). The tendency of IL 4mRNA expression was similar with that of IL 4 protein. As for fungal loads in kidneys, CFUs were significantly higher on day 7 than on day 3 after infection . Mice in both groups succumbed to infection within several days. It was suggested that IL 4 might play a promoting role in the development of murine systemic Candidiasis.

Inhibitory effect of heparin-derived oligosaccharides on secretion of interleukin-4 and interleukin-5 from human peripheral blood T lymphocytes

AIM: To investigate the inhibitory effect of heparin-derived oligosaccharides (Oligs) on secretion of interleukin-4 (IL-4) and interleukin-5 (IL-5) from human peripheral blood T lymphocytes (PBTLs).METHODS: Oligs were prepared by three different heparin depolymerization methods and separated by gel filtration chromatography. PBTLs from ten adult patients with allergic eosinophilic gastroenteritis were treated with phytahematoagglutinin (PHA) and Oligs. The supernatants from the cell culture of PBTLs were harvested and subjected to the determination of IL-4 and IL-5 contents by ELISA method.RESULTS: At the concentration of 5μg/mL, Oligs with different Mr had different effects on the secretion of IL-4 and IL-5. The tetrasaccharide with Mr of 1 142, produced by depolymerizing heparin with hydrogen peroxide, had the strongest inhibitory effect on the secretion of IL-4. It decreased the IL-4 content from 375.6±39.2 ng/L (PHA group) to 12.5±5.7 ng/L (P<0.01). The hexasaccharide with Mr of I 806, produced by depolymerizing heparin with βelimination method, had the strongest inhibitory effect on the secretion of IL-5. It decreased the IL-5 content from 289.2±33.4 ng/L (PHA group) to 22.0±5.2 ng/L (P<0.01).CONCLUSION: The inhibitory activity of Oligs on the secretion of IL-4 and IL-5 from human PBTLs closely depends on their molecular structure, and there may be an essential structure to act as an inhibitor. The most effective inhibitors of IL-4 and IL-5 secretion are tetrasaccharides and hexasaccharides, respectively.

The Role of Antioxidant Vitamin C on Imminent Abortion through Interaction of Superoxide Dismutase, Interferon-γ, Interleukin-4, Vascular Cells Adhesion Molecule-1, and Decidual Spiral Arteries Blood Flow

Imminent abortion needs more serious attention since it remains a big problem in Indonesia considering its epidemiology, morbidity, mortality,?and prognosis. In fact, some cases can still be prevented.?The objective of this study was to determine pathogenesis, diagnosis,?and prognosis of imminent abortion through the role of antioxidant vitamin C in the interaction of superoxide dismutase (SOD), interferon-γ?(IFN-γ), interleukin-4 (IL-4), vascular cells adhesion molecule-1?(VCAM-1), and decidual spiral artery resistance index (DSA RI).?This study took 10 months from March to December 2007 at Obstetrics and Gynecology Department of Medical Faculty of?Padjadjaran?University/Hasan Sadikin Hospital, Bandung. Sixty pregnant women who met the inclusion and exclusion criteria were divided into two groups with the random clinical trial method, double-blind with?repeated measurements.?Data were analyzed statistically using t test, Mann-Whitney, Rank?Spearman, Wilcoxon, t paired, and diagnostic test.?The results of this study showed that the incidence of abortion in vitamin C group was 9 cases (30%) and placebo group was 13 cases (43.3%). There was a significant difference in SOD, IFN-γ, IL-4 and VCAM-1 level between groups of women with and without abortion (p < 0.001).?There was a significant difference of SOD level between women with abortion 655.8 (163.6) U/gHb and placebo group 824.5 (106.7) U/gHb after vitamin C administration (p = 0.008). The cutoff point of SOD?was?￡992 U/gHbwhich?showed quite high sensitivity, specificity, accuracy,?and significant difference (p < 0.001). The cutoff point abortion of DSA resistance index was ≥0.55 with 45% accuracy (p = 0.002). The highest change of IL-4 level was 60.7% in vitamin C group and VCAM-1 was?-2.2% (p < 0.05) after?vitamin C administration. There was a negative correlation in SOD changes toward IL-4 changes after vitamin C administration (r =?-0.523) (p = 0.003), a positive correlation between SOD changes and IL-4 changes (0.597) (p < 0.001), a negative correlation between SOD changes and VCAM-1 changes (r =?-0.737) (p < 0.001) and a negative correlation between SOD changes and DSA RI changes (r =?-0.208) (p = 0.022). There were significant changes in the increment of IL-4 and SOD level (p < 0.001) and a decline in IFN-γ, VCAM-1 and DSA RI (p < 0.001) before and after vitamin C administration. In conclusion, there?was a correlation between the?increase of SOD level with?the?decrease of INF-γ?level and?the?increase of IL-4 level in imminent abortion after vitamin C administration. There?was a correlation between?the?increase of SOD level with?the?decrease of DSA RI and?the?decrease of VCAM-1 level in imminent abortion after vitamin C administration. In abortion, there?was?a?decrease of SOD and IL-4 level,?as well as an?increase of IFN-γ, VCAM-1, and DSA RI level.

血管生成素样蛋白4通过调节成纤维细胞和内皮细胞功能影响糖尿病足进程

背景:研究表明,血管因素对糖尿病足的发生具有重要影响。目的:探讨血管生成素样蛋白4在糖尿病足形成中的重要作用。方法:①对糖尿病足患者的基因表达谱数据进行生物信息学分析,找到关键基因。收集糖尿病足患者以及无糖尿病健康人的皮肤标本进行苏木精-伊红染色、免疫组化染色以及qRT-PCR实验,检测血管生成素样蛋白4表达情况。②培养人永生化皮肤成纤维细胞系和原代人脐静脉内皮细胞,将2种细胞分别分为对照组和外源性补充血管生成素样蛋白4组,通过划痕实验以及CCK-8实验分别检测成纤维细胞的迁移能力和增殖能力,通过Ki67实验检测内皮细胞的增殖能力。结果与结论:①生信分析发现,血管生成素样蛋白4基因的下调可能是导致糖尿病足形成的关键基因。②苏木精-伊红染色结果显示,与正常皮肤相比,血管生成素样蛋白在糖尿病足皮肤内弱表达,且其mRNA水平相对表达量降低(P<0.01)。③划痕实验结果显示,与对照组相比,血管生成素样蛋白4组成纤维细胞迁移能力明显增强;CCK-8细胞增殖实验显示,血管生成素样蛋白4组成纤维细胞的吸光度值在24,48 h均高于对照组(P<0.01,P<0.001);提示血管生成素样蛋白4可增强高糖处理的成纤维细胞迁移及增殖能力。④Ki67实验结果显示,与对照组相比,血管生成素样蛋白4组内皮细胞Ki67阳性细胞数目明显多于对照组;CCK-8细胞增殖实验显示,血管生成素样蛋白4组内皮细胞的吸光度值在24,48 h均高于对照组(P<0.05,P<0.001)。(5)以上结果均提示血管生成素样蛋白4可增强高糖处理内皮细胞的增殖能力。

六方Al_(4)SiC_(4)弹性性质、电子结构和光学性质的第一性原理计算

采用基于密度泛函理论(DFT)的第一性原理计算方法系统地研究了Al_(4)SiC_(4)的晶体结构、弹性常数、电子结构和光学性质,并对结果进行了理论分析.计算得到的晶格常数和弹性常数均与实验值及其它计算值相符,并说明了六方Al_(4)SiC_(4)的晶体结构是稳定的;计算得到了六方Al_(4)SiC_(4)的体积、剪切、杨氏模量及泊松比与文献值一致,Al_(4)SiC_(4)的禁带宽度为1.076 eV.计算得到了六方Al_(4)SiC_(4)在(100)和(001)方向上的光学响应函数随光子能量的变化关系,包括复介电函数、复折射率、吸收光谱及反射光谱.在(100)和(001)方向上,计算得到其静态介电常数分别为7.74和8.96,折射率分别为2.78和2.99.计算结果可以为相关应用提供理论依据.

单轴应变对本征和N掺杂4H-SiC电子结构的影响

采用基于密度泛函理论的第一性原理方法,研究了单轴应变对本征和N掺杂4H-SiC电子结构的影响.研究表明应变可以有效调控本征和N掺杂4H-SiC的带隙,在拉应变作用下,带隙单调减小;而在压应变作用下,带隙先增大后减小,当压应变为-1%时,带隙达到最大值.对态密度的分析可知本征和N掺杂4H-SiC的价带顶主要来自Si 3p和C 2p态电子,导带底主要来自Si 3p态电子,C 2p态和Si 3p态通过影响价带顶和导带底从而导致应变结构中带隙发生变化.通过Mulliken布局和差分电荷密度分析可知,随着晶格常数的增加Si原子向C原子和N原子转移的电荷减少,同时Si-C原子和Si-N原子之间的共价性减弱.

ACSL4介导铁死亡及在动脉粥样硬化性心血管病中的潜在作用

背景:铁死亡是一种铁依赖性调节细胞死亡形式,其特征是铁依赖性脂质过氧化,长链酰基辅酶A合酶4参与脂质过氧化底物的形成进而导致铁死亡。近几年研究表明,长链酰基辅酶A合酶4介导铁死亡在动脉粥样硬化性心血管疾病中发挥关键作用。目的:总结长链酰基辅酶A合酶4的结构功能和调控机制及其介导铁死亡的潜在分子机制,阐述长链酰基辅酶A合酶4驱动铁死亡在动脉粥样硬化、缺血性脑卒中和心肌梗死中的应用,以期为治疗动脉粥样硬化心血管疾病提供新的治疗策略。方法:在PubMed数据库检索自建库起至2023年8月收录的相关文献,以“atherosclerosis,ferroptosis,long-chain acyl-coenzyme A synthase 4,ACSL4,glutathione peroxidase 4,ischemic stroke,myocardial infarction,endothelial cell,smooth muscle cells,foam cell”为检索词,最终纳入76篇文献进行综述分析。结果与结论:①长链酰基辅酶A合酶4参与形成多不饱和脂肪酸的辅酶衍生物并将其插入磷脂,为铁死亡发生的核心机制脂质过氧化提供底物;②在长链酰基辅酶A合酶4表达的调节因子中,整合素α6β4、细胞内囊泡转运因子p115、锌脂蛋白A20负调控其表达,同时多种miR通过结合3′-UTR下调其表达,相反长链酰基辅酶A合酶4的表达上调大部分通过转录因子转录调控;③长链酰基辅酶A合酶4依赖性生成含有多不饱和脂肪酸的磷脂是脂质过氧化并执行铁死亡必不可少的必要条件,且长链酰基辅酶A合酶4与谷胱甘肽过氧化酶4作为铁死亡的正负调控因子相互制约,其具体机制仍待进一步研究;④长链酰基辅酶A合酶4介导铁死亡参与动脉粥样硬化、心肌梗死、缺血性脑卒中的病理机制,动脉粥样硬化中内皮细胞损伤与长链酰基辅酶A合酶4介导的铁死亡密切相关,但长链酰基辅酶A合酶4参与泡沫细胞形成、平滑肌细胞表型转化、钙化的研究尚未见报道;⑤长链酰基辅酶A合酶4作为铁死亡的生物标志物和潜在靶点成为研究热点,靶向长链酰基辅酶A合酶4抑制铁死亡可能成为治疗动脉粥样硬化性心血管疾病的新方向,而抑制长链酰基辅酶A合酶4的药物研究较少,未来还需进一步研究。

MgN_(4)掺杂石墨烯CO氧化催化活性的密度泛函研究

鉴于镁卟啉所呈现的催化活性,采用密度泛函理论考察了MgN_(4)结构掺杂石墨烯的CO氧化催化活性.研究发现MgN_(4)掺杂石墨烯具有良好的结构稳定性,O_(2)优先吸附在金属活性位点且不易解离.其CO氧化以Eley-Rideal(ER)机理实现,决速步能垒仅为0.67 eV,与FeC_(3)、AlN_(4)掺杂石墨烯具有相当的催化活性.MgN_(4)掺杂石墨烯有望是一种具有潜在CO氧化催化活性的催化剂.