Interleukin-1 receptor associated kinase 2 is a functional downstream regulator of complement factor D that controls mitochondrial fitness in diabetic cardiomyopathy

Diabetic cardiomyopathy is a disorder of the cardiac muscle that affects patients with diabetes.The exact mechanisms underlying diabetic cardiomyopathy are mostly unknown,but several factors have been implicated in the pathogenesis of the disease and its progression towards heart failure,including endothelial dysfunction,autonomic neuropathy,metabolic alterations,oxidative stress,and alterations in ion homeostasis,especially calcium transients[1].In Military Medical Research,Jiang et al.[2]sought to determine the functional role of complement factor D(Adipsin)in the pathophysiology of diabetic cardiomyopathy.

1BL·1RS染色体对小麦产量和品质相关性状的遗传效应分析

【目的】1BL·1RS易位系在小麦育种中应用广泛。解析不同背景下1BL·1RS染色体对小麦产量和品质相关性状的遗传效应,并分析其在生产中的应用情况,可为高产优质小麦的选育提供参考。【方法】244份自然群体和科农9204、京411为亲本构建的188个重组自交系(KJ-RIL-F8)为试验材料,利用1RS特异性分子标记对其进行基因型鉴定,结合表型数据分析,明确1BL·1RS易位系对产量和品质遗传效应。通过分析1BL·1RS易位系在不同年代审定品种中的占比,明确其在生产中的选择利用情况。【结果】188份KJ-RILs试验材料中有74份为1BL·1RS易位系,其产量相关性状分析表明,1BL·1RS易位系在高低氮条件下均显著延长小麦抽穗期,增加籽粒含氮比、旗叶长和旗叶面积,显著降低穗粒数,而对单株穗数、千粒重和旗叶宽3个性状的影响均不显著;其品质相关性状分析表明,1BL·1RS易位系在高低氮条件下均显著提高小麦的吸水率、湿面筋含量、蛋白质含量和籽粒硬度,而对容重、延展性和沉降值3个性状的影响均不显著。244份自然群体试验材料中,有76份为1BL·1RS易位系,其产量性状效应分析表明,1BL·1RS易位系可以显著增加穗粒数、穗长和小穗数,显著降低株高,而对单株穗数、千粒重、旗叶长、旗叶宽、旗叶面积5个性状的影响均不显著。将244份自然群体试验材料按照不同麦区和品种审定时间进行分类,对1BL·1RS易位系在生产中的应用情况进行分析,结果表明,不同麦区1BL·1RS易位系的占比差异较大,从20世纪90年代开始,1BL·1RS易位系在生产中的选择利用比例开始增加。【结论】高低氮对1BL·1RS易位系的效应影响不明显。1BL·1RS易位系在KJ-RIL群体和自然群体中对产量性状的效应不一致,这可能由于两者遗传背景不同所致。

Analyze interleukin-1β,interleukin-6,and tumor necrosis factor-αlevels in dry eye and the therapeutic effect of cyclosporine A

BACKGROUND Dry eye is a common eye disease.Artificial tears supplements are widely used for the treatment of dry eyes.However,multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears,which may affect the therapeutic effect.AIM To analyze the characteristics of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A.METHODS A total of 124 dry eye patients treated at The First People’s Hospital of Xining from April 2020 to April 2022 were selected as the observation group,while 20 healthy individuals served as the control group during the same period.Levels of inflammatory markers,including IL-1β,IL-6,and TNF-α,were analyzed.The observation group was further divided into a study group and a control group,each consisting of 62 patients.The control group received artificial tears,whereas the study group received a combination of artificial tears and cyclosporine A.Inflammatory markers,Schirmer’s test(SIT),tear break-up time(TBUT),corneal fluorescein staining(CFS),National Eye Institute Visual Function Questionnaire-25(NEI-VFQ-25)scores,and adverse events(AEs)were compared between the two groups.RESULTS The observation group exhibited significantly elevated serum levels of IL-1β,IL-6,and TNF-αin comparison to the healthy group.Following treatment,the study group demonstrated substantial reductions in IL-1β,IL-6,and TNF-αlevels relative to the control group.Moreover,after treatment,the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group.Additionally,significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia,foreign body sensation,fatigue,red eye,and burning sensation within the study group.Furthermore,post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group(P<0.05).It is noteworthy that significant AEs were reported in both groups throughout the treatment period.CONCLUSION Cyclosporine A combined with artificial tears is effective in treating dry eye,yielding enhanced outcomes by improving SIT and TBUT levels,reducing CFS scores,and ameliorating vision-related quality of life.

Interleukin-1β:Friend or foe for gastrointestinal cancers

Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and liver.Interleukin-1β(IL-1β)is a leukocytic pyrogen recognized as a tumor progression-related cytokine.IL-1βsecretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3,inflammasome formation,and activation of IL-1 converting enzyme.Several studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments,promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in vivo.The application of IL-1β inhibitors is also promising for targeted therapy development in some cancer types.However,as a leukocytic pro-inflammatory cytokine,IL-1β may also possess anti-tumorigenic effects and be type-specific in different cancers.This editorial discusses the up-to-date roles of IL-1β in GI cancers,including underlying mechanisms and down-stream signaling pathways.Understanding and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.

利用小麦-黑麦1BL.1RS易位系快速筛选F_(2)群体中携带抗条锈病基因Yr15的纯合个体

【目的】为了从F_(2)分离群体中快速鉴定含Yr15基因的纯合个体,从而减少后续选择的工作量。【方法】利用感条锈病的小麦-黑麦1BL.1RS易位系与含Yr15基因的小麦品系杂交,利用基于寡核苷酸探针Oligo-1RNOR的简便NDFISH方法对F_2群体进行鉴定。【结果】可以快速筛选出不含1BL.1RS易位染色体的植株,这些植株含1对1B染色体。因1BS不与1RS发生重组,所以它们都是含有Yr15基因的纯合个体,他们的自交后代不会出现抗感分离。【结论】这一方法可以提高Yr15的应用效率。对于其他小麦染色体携带的抗病基因,也可以采用这一方式,利用不同的小麦-黑麦易位染色体,从分离世代中快速鉴定出含抗病基因的纯合个体。该方法有利于加快小麦育种进程。

BL02U1:the relocated macromolecular crystallography beamline at the Shanghai Synchrotron Radiation Facility

Macromolecular crystallography beamline BL17U1 at the Shanghai Synchrotron Radiation Facility has been relocated,upgraded,and given a new ID(BL02U1).It now delivers X-rays in the energy range of 6–16 keV,with a focused beam of 11.6μm×4.8μm and photon flux greater than 1012 phs/s.The high credibility and stability of the beam and good timing synchronization of the equipment significantly improve the experimental efficiency.Since June 2021,when it officially opened to users,over 4200 h of beamtime have been provided to over 200 research groups to collect data at the beamline.Its good performance and stable operation have led to the resolution of several structures based on data collected at the beamline.

Changes of gastric and intestinal blood flow, serum phospholipase A_2 and interleukin-1β in rats with acute necrotizing pancreatitis

AIM:To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane. Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-1β levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62±0.06 and 0.35±0.05) mL/(min·g) was significantly lower than that in control group (0.86±0.11 and 0.85±0.06) mL/(min·g) (P<0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80±0.07 and 0.50±0.06) mlV(min·g) was significantly lower than that in control group (1.56±0.18 and 1.61±0.11) mL/(min·g) (P<0.01). Serum PLA2 activities (94.29±9.96 and 103.71± 14.40) U/L and IL-1β levels (0.78±0.13 and 0.83±0.20)μg/L in ANP group were higher than those in control group (65.27±10.52 and 66.63±9.81) U/L, (0.32±0.06 and 0.33±0.07)μg/L (P<0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P<0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred. CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are important pathogenic factors for gastric and intestinal mucosal injury in ANP.

Interleukin-1:an important target for perinatal neuroprotection?

Perinatal inflammation is a significant risk factor for lifelong neurodevelopmental impairments such as cerebral palsy.Extensive clinical and preclinical evidence links the severity and pattern of perinatal inflammation to impaired maturation of white and grey matters and reduced brain growth.Multiple pathways are involved in the pathogenesis of perinatal inflammation.However,studies of human and experimental perinatal encephalopathy have demonstrated a strong causative link between perinatal encephalopathy and excessive production of the pro-inflammatory effector cytokine interleukin-1.In this review,we summarize clinical and preclinical evidence that underpins interleukin-1 as a critical factor in initiating and perpatuating systemic and central nervous system inflammation and subsequent perinatal brain injury.We also highlight the important role of endogenous interleukin-1 receptor antagonist in mitigating interleukin-1-driven neuroinflammation and tissue damage,and summarize outcomes from clinical and mechanistic animal studies that establish the commercially available interleukin-1 receptor antagonist,anakinra,as a safe and effective therapeutic intervention.We reflect on the evidence supporting clinical translation of interleukin-1 receptor antagonist for infants at the greatest risk of perinatal inflammation and impaired neurodevelopment,and suggest a path to advance interleukin-1 receptor antagonist along the translational path for perinatal neuroprotection.

Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

Expression of Pigment Epithelium-derived Factor in Bladder Tumour Is Correlated with Interleukin-8 yet Not with Interleukin-1α

Pigment epithelium-derived factor （PEDF） is an antiangiogenic factor which is effective in tumour inhibition in a variety of tumours and has not yet been studied in bladder tumour before. In this study the expression of PEDF, interleukin-1α （IL-1α） and -8 （IL-8） in bladder tumours was investigated. Immunohistochemistry was performed on 64 bladder tumour and 23 normal uroepithelium samples. Expression change of the factors was compared with clinicopathological parameters. Correlations between PEDF, IL-1α and IL-8 were analyzed. None of the factors was in relation to gender, tumour occurrence, and size or onset pattern. PEDF （P=0.014） and IL-1α （P=0.049） expression was down-regulated with grade progression. PEDF expression was lower in normal uroepithelium than in papillary urothelial neoplasm of low malignant potential （PUNLMP） （P=0.000） and carcinoma （P=0.009） whilst IL-1α （P=0.000 and P=0.000 respectively） and IL-8 （P=0.000 and P=0.023 respectively） expression was higher in the same grouping. PEDF expression had a negative correlation with IL-8 in PUNLMP （P=0.049, r=-0.578） as well as in tumour grouping （P=0.033, r=-0.276）. Deranged expressional change of PEDF, IL-1α and IL-8 could be in relation to loss of differentiation from normal uroepithelium to papillary lesion and eventually to carcinoma.

Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization

Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.

EFFECT OF INTERLEUKIN-1β ON GROWTH HORMONE GENE EXPRESSION AND ITS POSSIBLE MOLECULAR MECHANISM IN RAT MtT/S SOMATOTROPH CELLS

Objective To elucidate the effect of interleukin-1β （IL- 1β） on human growth hormone （hGH） gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly established by transfecting 484-Lucl plasmid which contained hGH gene promoter --484 to ＋30 bp and luciferase reporter gene. The effect of IL-1β on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. Results The 10^3 U/mL IL-1β stimulated secretion and synthesis of GH, and promoted the 5＇-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase （MAPKK/MEK） inhibitor PD98059 （40 μmol/L） and p38 mitogen-activated protein kinase （MAPK） inhibitor SB203580 （5 μmol/L） completely blocked the stimulatory effect of IL-1μ, and phosphatidylinositol-3-kinase （PI3-K） inhibitor LY294002 partly abolished the effect of IL-1μ. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit- 1 nor inhibition of Pit- 1 expression affected induction of hGH promoter activity by IL-1μ. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1β, and results showed that the stimulatory effect of IL-1β was abolished following deletion of the --196 to -- 132 bp fragment. Conclusions IL-1β promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1β on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein.

东北春小麦抗秆锈病基因Sr31的分子检测及其抗性分析

为促进东北春小麦抗性育种,利用与抗秆锈病基因Sr31连锁的分子标记SCSS30.2和iag95,对300份东北春小麦抗秆锈病基因进行分子检测及抗性分析。结果表明,在300份春小麦品种中,有8份小麦品种被检测到含有iag95或SCSS30.2分子标记,含有抗秆锈病Sr31基因,而小麦品种农林45号中只鉴定到了含有iag95标记,钢09-558中只鉴定到了含有SCSS30.2标记。通过ω-sec标记,发现9.67%的供试材料含有1BL/1RS易位系。其中,同时携带与抗性基因Sr31连锁的两个标记SCSS30.2和iag95的8份材料,均被检测到含有1BL/1RS易位系。田间抗性鉴定进一步表明,被SCSS30.2检测到的9个材料中,除黑春1号外,其余材料在田间均表现出了极强的抗病性。而仅被iag95标记检测到的农林45号,对21C3CTHQM和34MKGQM两类生理小种均表现为感病。本研究成功鉴定出携带Sr31基因及1BL/1RS易位系的小麦材料,可作为小麦抗病育种材料进一步利用。

The role of Interleukin-1 family in cardiovascular disease and its research progress

The interleukin-1 family is a group of important cytokines that play a key regulatory role in the immune and inflammatory response(including infectious and non-bacterial injuries).Nowadays,the interleukin-1 family mainly includes 11 cytokines and has multiple roles in the pathology and physiology of inflammation.Moreover,accumulating number of research show that the interleukin-1 family and its receptors are involved in the occurrence and development of cardiovascular diseases.Therefore,we show here the review involving hotspots of the interleukin-1 family in the process of inflammation and its target therapy in cardiovascular diseases,including atherosclerosis,myocardial infarction and heart failure.

The remedial effect of soluble interleukin-1 receptor type Ⅱ on endometriosis in the nude mouse model

Objective： Recent studies have shown that the local expression of soluble interleukin （IL） -1 receptor type Ⅱ （slL-1 R Ⅱ ） in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 R Ⅱ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of slL-1-R Ⅱ administration on endometriosis in the nude mouse model. Methods： Nineteen nude model mice with endometriosis were randomly divided into three groups： group A was treated by intraperitoneal administration with only slL-1 R Ⅱ for two weeks, group B was similarly treated with only IL- 1, and group C （control） was administered saline. After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor （VEGF） and B-cell lymphoma leukemia-2 （Bcl- 2） were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid （PF） and serum were also measured by enzyme-linked immunosorbent assay （ELISA）. Results： The mean size of ectopic endometrial lesion did not differ between the three groups （P 〉 0.05）. Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion： slL-1 R Ⅱ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.

Elevated pancreatic enzymes, IgM, soluble interleukin-2 receptor in anti-GADab(+) type 1 diabetes

Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.

Hypoxia inducible factor 1α promotes interleukin-1 receptor antagonist expression during hepatic ischemia-reperfusion injury

BACKGROUND Ischemia-reperfusion injury(IRI) is a major risk associated with liver surgery and transplantation,and its pathological mechanism is complex.Interleukin-1 receptor antagonist(IL-1ra) can protect the liver from IRI.However,the regulatory mechanism of IL-1ra expression is still unclear.AIM To identify the mechanism that could protect the liver in the early stage of IRI.METHODS To screen the key genes in hepatic IRI,we performed RNA sequencing and gene enrichment analysis on liver tissue from mice with hepatic IRI.Subsequently,we verified the expression and effect of IL-1ra in hepatic IRI.We also used promoter mutagenesis and chromatin immunoprecipitation assay to search for the transcriptional regulatory sites of hypoxia-inducible factor(HIF)-1α.Finally,to explore the protective mechanism of ischemic preconditioning(IP),we examined the expression of HIF-1α and IL-1ra after IP.RESULTS We identified IL-1ra as a key regulator in hepatic IRI.The expression of IL-1ra was significantly upregulated after hepatic IRI both in vivo and in vitro.Furthermore,we found that HIF-1αregulated Il-1ra transcription in response to hypoxia.Increased HIF-1α accumulation promoted IL-1ra expression,whereas inhibition of HIF-1α exhibited the opposite effect.We also confirmed a predominant role for hypoxia response element in the regulation of Il1ra transcription by HIF-1αactivation.Of note,we demonstrated that IP protects against hepatic IRI by inducing IL-1ra expression,which is mediated through HIF-1α.CONCLUSION We demonstrated that ischemia or hypoxia leads to increased expression of IL-1ra through HIF-1α.Importantly,IP protects the liver from IRI via the HIF-1α–IL-1ra pathway.

Autocrine IL-8 Contributes to Propionibacterium Acnes-induced Proliferation and Differentiation of HaCaT Cells via AKT/FOXO1/Autophagy

Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P.acnes-induced keratinocytes,suggesting a potential therapeutic target for AV.

顺铂诱导肾损伤模型在C57BL/6小鼠J和N亚型中的差异性研究

目的探讨C57BL/6 J和N亚型小鼠在顺铂诱导肾损伤模型中的易感性差异,为选择药物肾损伤模型提供理论依据。方法雄性C57BL/6小鼠J和N两种亚型,各随机分为正常组(Control)、模型组(cisplatin,CDDP)。模型组腹腔注射顺铂(3.33 mg·kg^(-1)),隔天给药,持续2周,记录小鼠体重变化、存活率;检测Scr、BUN和β2-MG评价肾功能;HE、Masson和PAS染色法观察肾皮质病理改变。IL-6、IL-1β和IL-18等炎症因子检测顺铂导致的肾脏炎症反应。结果与Control组相比,CDDP组两种亚系小鼠Scr、BUN和β2-MG均明显升高;组织学结果显示肾小管损伤,胶原纤维化和糖原沉积均增加;IL-6、IL-1β和IL-18炎症因子含量和肾皮质蛋白表达均明显升高。C57BL/6N与C57BL/6J系小鼠比较,C57BL/6N系小鼠肾功能指标Scr和BUN均值明显偏高(P<0.01),组织学评分各病理损伤较C57BL/6J亚系小鼠明显偏高,反映纤维化的Masson染色差异具有统计学意义(P<0.01);IL-6、IL-1β和IL-18均值明显偏高,但差异无统计学意义。结论C57BL/6 J和N亚型小鼠均可使用顺铂诱导成功肾损伤模型,相比于C57BL/6J小鼠,C57BL/6N亚系小鼠在肾功能、组织学以及炎症因子等方面损伤明显,提示C57BL/6N亚系小鼠更适于作为药物或者其他肾功能损伤模型的建立。

血清TIMP-1、YKL-40、CRP及ANCA在学龄期支气管炎诊断及预后评估中的价值

【目的】探讨血清基质金属蛋白酶抑制物-1(TIMP-1)、人软骨糖蛋白39(YKL-40)、C反应蛋白(CRP)、抗中性粒细胞胞浆抗体(ANCA)在学龄期支气管炎诊断及预后评估中的价值。【方法】选取100例学龄期支气管炎患儿作为观察组,接受体检的100名健康学龄期儿童作为对照组。观察组行常规治疗1~2周后,按疗效分为预后良好组和预后不良组。比较两组儿童TIMP-1、YKL-40、CRP及ANCA水平,采用受试者工作特征(ROC)曲线分析TIMP-1、YKL-40、CRP及ANCA诊断学龄期支气管炎的价值。比较治疗前后及预后良好组和预后不良组患儿TIMP-1、YKL-40、CRP及ANCA水平,对患儿预后和TIMP-1、YKL-40、CRP及ANCA行相关性分析。【结果】观察组血清TIMP-1、YKL-40、CRP及ANCA水平显著高于对照组(P<0.05)。ROC曲线分析证实,TIMP-1≥228.510 pg/mL、YKL-40≥26.755 ng/L、CRP≥12.130 mg/L、ANCA≥167.850 AU/mL可用于学龄期支气管炎的诊断,曲线下面积分别为0.895、0.892、0.874、0.866(均P<0.05)。治疗后,观察组患儿TIMP-1、YKL-40、CRP及ANCA较治疗前均显著降低(P<0.05)。预后良好组患儿四项指标均低于预后不良组(P<0.05),且其均与学龄期支气管炎患儿预后呈正相关。【结论】支气管炎患儿血清TIMP-1、YKL-40、CRP及ANCA较正常儿童水平高,治疗后各项指标均下降,其与患儿预后呈正相关,临床上可通过检测血清TIMP-1、YKL-40、CRP及ANCA水平来辅助诊断学龄期支气管炎及评估患儿预后。