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.

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.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study

BACKGROUND The interplay between inflammation,immune dysregulation,and the onset of neurological disorders,including epilepsy,has become increasingly recognized.Interleukin(IL)-6,a pro-inflammatory cytokine,is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients.The role of IL-6 receptor(IL6R)blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes.neuropsychiatric conditions due to neuroinflammation.METHODS Mendelian randomization(MR)analysis employing single nucleotide poly-morphisms(SNPs)in the vicinity of the IL6R gene(total individuals=408225)was used to evaluate the putative causal relationship between IL6R blockade and epilepsy(total cases/controls=12891/312803),focal epilepsy(cases/controls=7526/399290),and generalized epilepsy(cases/controls=1413/399287).SNP weights were determined by their effect on C-reactive protein(CRP)levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects.To address potential outlier and pleiotropic influences,sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions.RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk[inverse variance weighting:Odds ratio(OR):0.827;95%confidence interval(CI):0.685-1.000;P=0.05].Subtype analysis showed variability,with no significant effect observed in generalized,focal,or specific childhood and juvenile epilepsy forms.Beyond the primary inflammatory marker CRP,the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy,hinting at possible links to neuroinflammation,psychiatric symptoms,and associated mental disorders.CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence,likely mediated via complex neuroinflammatory pathways.These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy.The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

Variability of the Pacific subtropical cells under global warming in CMIP6 models

The Pacific subtropical cells(STCs)are shallow meridional overturning circulations connecting the tropics and subtropics,and are assumed to be an important driver of the tropical Pacific decadal variability.The variability of STCs under global warming is investigated using multimodal outputs from the latest phase of the Coupled Model Inter-comparison Project(CMIP6)and ocean reanalysis products.Firstly,the volume transport diagnostic analysis is employed to evaluate how coupled models and ocean reanalysis products reproduce interior STC transport.The variation of heat transport by the interior STC under the high-emissions warming scenarios is also analyzed.The results show that the multimodal-mean linear trends of the interior STC transport along 9°S and 9°N are-0.02 Sv/a and 0.04 Sv/a under global warming,respectively,which is mainly due to the combined effect of the strengthened upper oceanic stratification and the weakening of wind field.There is a compensation relationship between the interior STC and the western boundary transport in the future climate,and the compensation relationship of 9°S is more significant than that of 9°N.In addition,compared with ocean reanalysis products,the coupled models tend to underestimate the variability of the interior STC transport convergence,and thus may lose some sea surface temperature(SST)driving force,which may be the reason for the low STC-SST correlation simulated by the model.The future scenario simulation shows that the heat transport of interior STC is weakened under global warming,with a general agreement across models.

Effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients

Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who were undergoing spinal fusion surgery for disc herniation were administered flurbiprofen 100 mg (P group, flurbiprofen group), prednisolone 0.6 mg/kg (D group, prednisolone group), prednisolone 0.6 mg/kg plus flurbiprofen 100 mg (P + D group, flurbiprofen + prednisolone group) or normal saline (S group, saline group) 15 minutes before the induction of anesthesia. Plasma samples were collected before surgery (T0) and on day 1 (T1), day 2 (T2) and day 3 (T3) following surgery. At the same time, systemic inflammatory response syndrome (SIRS) was assessed by SIRS criteria. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) for collected samples were measured. Results: Other groups had significantly lower levels of IL-6, CRP and occurrence of SIRS than S group (p < 0.05). Compared to groups P and D, the levels of IL-6 and CRP in P + D group were significantly lower on T1 (p < 0.05). Peak levels of IL-6 in all groups were presented on T1 (p 0.05). The levels of CRP within three days were significantly different but did not show peak levels (p > 0.05). Conclusion: Compared to prednisolone or flurbiprofen, combining flurbiprofen with prednisolone in elderly surgery patients led to an increased suppression of IL-6.

Intermittent fasting boosts antitumor immunity by restricting CD11b^(+)Ly6C^(low)Ly6G^(low) cell viability through glucose metabolism in murine breast tumor model

Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.

Analysis of the Role of D-Dimer,Interleukin-6,and Interleukin-18 in Differential Diagnosis of Pediatric Refractory Mycoplasma pneumoniae Pneumonia

Objective:To analyze the value of D-dimer(D-D),interleukin-6(IL-6),and IL-18 in the differential diagnosis of children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods:The medical records of 92 children with Mycoplasma pneumoniae pneumonia(MPP)treated in the hospital were selected for retrospective analysis from January 2023 to January 2024.After comprehensive examinations such as computed tomography examination of the chest,48 children with general Mycoplasma pneumoniae pneumonia(GMPP)were put in the GMPP group and 44 children with RMPP were grouped in the RMPP group.The IL-6,IL-18,and D-D levels were compared between the two groups,and the receiver operating characteristic(ROC)curves were plotted to analyze their value for differential diagnosis of RMPP.Results:The levels of IL-6,IL-18,and D-D in the RMPP group were higher than those in the GMPP group(P<0.05);the ROC curves showed that the specificity of the differential diagnosis of IL-6,IL-18,and D-D was higher,and their diagnostic value was significant.Conclusion:Determination of IL-6,IL-18,and D-D levels in children with MPP can further diagnose the children’s condition,which can help physicians formulate targeted treatment plans,and is of great significance to the improvement of the children’s condition,which is worthy of attention.

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

Efficacy of Laparoscopic Cholecystectomy in Treating Patients with Gallstones and Its Effect on Interleukin-6 and Tumor Necrosis Factor-α Levels

Objective:To investigate the efficacy of laparoscopic cholecystectomy in the treatment of patients with gallstones and its effect on the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-a).Methods:A total of 82 patients with gallstones admitted from July 2020 to July 2023 were recruited and allocated into control and observation groups using the random number table method,with 41 cases in each group.The patients were treated with laparoscopic cholecystectomy,with the anterior triangle anatomical approach to the gallbladder in the control group and the posterior triangle anatomical approach to the gallbladder in the observation group.The treatment effect and inflammatory factor levels of both groups were observed and compared.Results:When comparing the clinical outcomes of both patient groups,the key parameters evaluated included time to mobilization,duration of surgery,extubation time,and intraoperative bleeding.The observation group exhibited a significant advantage in these parameters compared to the control group(P<0.05).Regarding the levels of inflammatory factors between the two groups before and after treatment,there was no significant difference in values before treatment.However,following treatment,patients in the observation group showed significantly lower levels of IL-6,TNF-α,and C-reactive protein(CRP)compared to the control group(P<0.05).Conclusion:Patients undergoing laparoscopic cholecystectomy for gallstones can benefit from the implementation of the posterior triangular anatomical approach to the gallbladder,which not only enhances therapeutic efficacy but also offers significant advantages in reducing levels of IL-6,TNF-α,and CRP.Therefore,it is recommended for the widespread adoption of this treatment approach in clinical practice.

6-Gingerol, asarinin, and deoxyschizandrin improve bronchial epithelium functions in an interleukin-13einduced BEAS-2B cell model

Objective:To explore the effects of 6-gingerol,asarinin,and deoxyschizandrindthe main components of Zingiber officinale(Willd.)Rosc.(Gan Jiang),Asarum heterotropoides f.var.mandshuricum(Maxim.)(Xi Xin),and Schisandra chinensis(Turcz.)Baill.(Wu Wei Zi),respectivelydon an interleukin(IL)-13einduced BEAS-2B cell model in vitro.Methods:The BEAS-2B cell model was established using 25 ng/mL IL-13 combined with 1%fetal bovine serum(FBS)in vitro.Mitoquinone mesylate(Mito-Q)treatment was used as a positive control group,and different concentrations of 6-gingerol,asarinin,and deoxyschizandrin were used to treat the models.The level of reactive oxygen species(ROS)production was detected by flow cytometry.The expression levels of LC3B,Beclin1,adenosine 50-monophosphate(AMP)eactivated protein kinase(AMPK),phosphory-lated-AMPeactivated protein kinase(P-AMPK),dynamin-related protein 1(DRP1),and mitochondrial fusion protein 2(MFN2)were detected by Western blot.Mitochondrial membrane potential(MMP)assay kit with JC-1 was utilized to detect the level of MMP.Results:The BEAS-2B cells exposed to 25 ng/mL IL-13 with 1%FBS showed an increased ROS level and a decreased MMP.6-Gingerol,asarinin,and deoxyschizandrin were able to downregulate ROS level and upregulate the MMP in the BEAS-2B model.Asarinin and deoxyschizandrin reduced the expression of autophagy protein LC3B,while deoxyschizandrin significantly increased the expression of DRP1 in the BEAS-2B model.Conclusion:6-Gingerol,asarinin,and deoxyschizandrin can reduce ROS generation and increase MMP,but have different regulatory effects on the expression of autophagy protein and mitochondrial mitotic protein.The three components have both synergistic and complementary effects in classic medicine compatibility.This study may provide an innovative strategy to reduce the lung inflammation related to IL-13.

miR-216a和CAPN6基因过表达人宫颈癌细胞系HeLa增殖迁移侵袭变化及靶向关系

目的观察微小RNA-216a(miR-216a)和钙蛋白酶6(CAPN6)基因过表达的人宫颈癌细胞系HeLa增殖、迁移、侵袭变化及靶向关系,探讨miR-216a对HeLa细胞增殖迁移侵袭影响的作用机制。方法取对数生长期HeLa细胞,分为一、二、三、四、五组,一组转染miR-216a mimic,二组转染pcDNA3.1-CAPN6质粒,三组顺序转染miR-216a mimic、pcDNA3.1-CAPN6,四组转染pcDNA3.1,五组转染miR-216a mimic NC,培养48 h时分别采用CCK-8法、划痕愈合实验、Transwell试验观察各组细胞的增殖迁移侵袭情况,培养24 h时采用qRT-PCR法检测各组细胞miR-216a、采用WesternBlotting法检测各组细胞CAPN6及信号转导子与激活子3(STAT3)蛋白。取对数生长期HeLa细胞分为四组:A组细胞顺序转染miR-216a mimic、pGL3-CAPN6-WT质粒,B组细胞顺序转染miR-216a mimic、pGL3-CAPN6-MUT质粒,C组细胞顺序转染miR-216amimicNC、pGL3-CAPN6-WT,D组细胞顺序转染miR-216amimicNC、pGL3-CAPN6-MUT,培养36 h时收集各组细胞,采用双荧光素酶报告基因检测试剂盒测算各组细胞相对荧光素酶活性。结果与五组相比,培养48 h时一组细胞增殖活性及划痕前缘迁移距离百分比低、侵袭细胞数少(P均<0.01);与四组相比,二组细胞增殖活性及划痕前缘迁移距离百分比高、侵袭细胞数多(P均<0.01);与一组相比,三组细胞增殖活性及划痕前缘迁移距离百分比高、侵袭细胞数多(P均<0.01);与二组相比,三组细胞增殖活性及划痕前缘迁移距离百分比低、侵袭细胞数少(P均<0.01)。与五组相比,一组细胞miR-216a相对表达量高(P<0.01)。与四组相比,培养24 h时二组细胞CAPN6蛋白、p-STAT3/STAT3相对表达量高,三组细胞表达CAPN6蛋白、p-STAT3/STAT3相对表达量低;与五组相比,一组细胞CAPN6蛋白、p-STAT3/STAT3相对表达量低;与一组相比,三组细胞CAPN6蛋白、p-STAT3/STAT3相对表达量高。与B组相比,A组细胞荧光素酶活性低(P<0.05)。结论miR-216a过表达可抑制HeLa细胞的增殖侵袭和迁移。HeLa细胞中miR-216a与CAPN6基因存在靶向关系。miR-216a可能通过调控CAPN6基因表达,抑制HeLa的增殖、迁移及侵袭。

血清转化生长因子β1、白细胞介素-6、Toll样受体-4、核转录因子κB联合评估非小细胞肺癌放射性肺炎病情严重程度的价值

目的探讨血清转化生长因子β1(TGF-β1)、白细胞介素-6(IL-6)、Toll样受体-4(TLR-4)和核转录因子κB(NF-κB)联合评估非小细胞肺癌(NSCLC)放射性肺炎(RP)病情严重程度的价值。方法选取104例NSCLC放疗后继发RP患者作为研究组,另选取52例NSCLC放疗后未继发RP患者作为对照组。比较2组患者放疗前后血清TGF-β1、IL-6、TLR-4、NF-κB水平。比较研究组不同程度RP患者放疗前后血清TGF-β1、IL-6、TLR-4、NF-κB水平,分析各血清指标单独及联合评估NSCLC放疗后RP病情程度的价值。结果放疗结束后,研究组患者血清TGF-β1、IL-6、TLR-4、NF-κB水平均高于对照组,差异有统计学意义(P<0.05);放疗结束后,随着RP病情程度的增加,研究组患者血清TGF-β1、IL-6、TLR-4、NF-κB水平呈升高趋势,差异有统计学意义(P<0.05)。受试者工作特征(ROC)曲线分析结果显示,放疗结束后血清TGF-β1、IL-6、TLR-4、NF-κB水平评估1级RP的曲线下面积(AUC)分别为0.787、0.718、0.783、0.801,评估≥2级RP的AUC分别为0.729、0.740、0.793、0.825;血清TGF-β1、IL-6、TLR-4、NF-κB阳性表达患者发生≥2级RP的风险分别是阴性表达患者的2.473、2.275、2.610、5.267倍(P<0.05);血清TGF-β1、IL-6、TLR-4、NF-κB联合评估≥2级RP的AUC为0.939,敏感度为76.00%,特异度为97.47%。结论NSCLC患者放疗结束后血清TGF-β1、IL-6、TLR-4、NF-κB水平均与RP病情严重程度呈正相关,四者联合评估≥2级RP的价值显著,可为临床控制RP病情提供参考依据。

基于METTL3介导的miR-29a-3p的m^(6)A修饰探讨平喘颗粒抑制气道上皮细胞泛凋亡治疗哮喘的机制研究

目的:观察平喘颗粒对METTL3介导的气道上皮细胞中miR-29a-3p的m^(6)A修饰的影响,明确其抑制哮喘气道炎症的分子机制。方法:16HBE采用LPS诱导(50 mg/L)构建细胞模型,并给予平喘颗粒含药血清和地塞米松进行干预。分别采用CCK8法检测细胞活性、ELISA法检测炎症因子(TNF-α、IL-6和IL-8)的含量和miR-29a-3p的m^(6)A修饰水平、Western blot检测METTL3与泛凋亡蛋白的表达和qRT-PCR检测METTL3与miR-29a-3p的表达。结果:与模型组相比,平喘颗粒能够显著增加16HBE的活力,抑制炎症因子TNF-α、IL-6和IL-8的含量,下调泛凋亡相关蛋白p-RIPK3、p-MLKL、cleaved Caspase-1、cleaved Caspase-3的表达和GSDMD-NT/FL-GSDMD与GSDME-NT/FL-GSDME的比值,差异均具有统计学意义(P<0.01)。此外,平喘颗粒能够显著上调细胞中miR-29a-3p和METTL3的表达水平,促进miR-29a-3p的m^(6)A修饰水平,与模型组相比差异均具有统计学意义(P<0.01)。结论:平喘颗粒主要通过METTL3增强miR-29a-3p的m^(6)A修饰水平,抑制气道上皮细胞泛凋亡,改善气道炎症。

非小细胞肺癌组织中circBIRC6、APPBP2表达及临床预后意义

目的 探讨非小细胞肺癌(NSCLC)组织中环状核糖核酸杆状病毒IAP重复序列6(circBIRC6)、β淀粉样蛋白前体蛋白结合蛋白2(APPBP2)表达及临床预后意义。方法 收集2018年6月~2020年1月90例在河北北方学院附属第一医院行手术切除的NSCLC组织及癌旁组织,采用实时荧光定量聚合酶链式反应检测circBIRC6、APPBP2表达,并分析二者与NSCLC患者临床病理特征的关系。通过Pearson相关性分析NSCLC组织中circBIRC6与APPBP2 mRNA表达的相关性,Kaplan-Meier法绘制不同表皮生长因子受体(EGFR)基因突变、TNM分期和circBIRC6、APPBP2 mRNA表达的NSCLC患者生存曲线,多因素Cox回归分析NSCLC患者预后的影响因素。结果 与癌旁组织比较,NSCLC组织中circBIRC6、APPBP2 mRNA表达升高(P<0.05)。NSCLC组织中circBIRC6与APPBP2 mRNA表达呈正相关(r=0.817,P<0.001)。NSCLC患者不同分化程度、TNM分期、淋巴结转移组织中circBIRC6、APPBP2 mRNA表达比较有差异(P<0.05)。随访3年,90例NSCLC患者总生存率为55.56%(50/90)。EGFR基因突变阳性/阴性NSCLC患者总生存率比较无差异(P>0.05);TNM分期Ⅰ~Ⅱ期NSCLC患者总生存率高于Ⅲ期NSCLC患者(P<0.05);circBIRC6、APPBP2 mRNA高表达组生存率低于circBIRC6、APPBP2 mRNA低表达组(P<0.05)。低分化、TNM分期Ⅲ期、淋巴结转移和circBIRC6≥10.97、APPBP2 mRNA≥2.48为NSCLC患者死亡的独立危险因素[OR(95%CI)=3.586(1.080~11.909)、3.632(1.193~11.057)、3.197(1.060~9.640)、3.223(1.086~9.570)、2.767(1.022~7.492)]。结论 NSCLC组织中circBIRC6、APPBP2 mRNA高表达,与分化程度、TNM分期、淋巴结转移和预后有关。

喉鳞状细胞癌组织中ATF6和IFN-α的表达与临床病理特征及预后的相关性研究

目的 探讨转录激活因子6(activating transcription factor 6,ATF6)和干扰素α(interferon α,IFN-α)在喉鳞状细胞癌(laryngeal squamous cell carcinoma,LSCC)组织中的表达及意义。方法 选取2015年3月~2020年3月于河南科技大学临床医学院/河南科技大学第一附属医院入院治疗的100例LSCC患者,收集整理其肿瘤部位、分化程度、淋巴结转移等临床病理特征;采用免疫组织化学法检测组织中ATF6和IFN-α的表达;采用Spearman法分析LSCC组织中ATF6与IFN-α表达的相关性;用Kaplan-Meier法分析LSCC组织中ATF6,IFN-α表达与患者三年生存率的关系;采用COX回归分析LSCC患者一年死亡的影响因素。结果 ATF6在LSCC组织中阳性率(76.00%)明显高于癌旁正常组织(13.00%),IFN-α在LSCC组织中阳性率(29.00%)明显低于癌旁正常组织(74.00%),差异具有统计学意义(χ^(2)=80.352,40.536,均P<0.05);TNM分期为Ⅲ+Ⅳ期、浸润深度为深层、发生淋巴结转移的LSCC患者ATF6阳性表达比例均显著高于TNM分期为Ⅰ+Ⅱ期、浸润深度为浅层、未发生淋巴结转移的LSCC患者(χ^(2)=7.310,9.223,5.123,均P<0.05)。TNM分期为Ⅲ+Ⅳ期、浸润深度为深层、发生淋巴结转移的LSCC患者IFN-α阴性表达比例均显著高于TNM分期为Ⅰ+Ⅱ期、浸润深度为浅层、未发生淋巴结转移的LSCC患者(χ^(2)=8.564,5.021,5.203,均P<0.05);LSCC组织中ATF6与IFN-α表达具有负相关性(r=-0.415,P<0.05);ATF6阳性表达组LSCC患者三年生存率(50.00%)显著低于ATF6阴性表达组(83.33%),IFN-α阳性表达组LSCC患者三年生存率(82.76%)显著高于IFN-α阴性表达组(47.89%)(Log rank χ^(2)=8.002,10.854,均P<0.05)。ATF6(HR=1.735,95%CI:1.159~2.598),IFN-α(HR=0.624,95%CI:0.439~0.886)均是LSCC患者死亡的影响因素(P<0.05)。结论 LSCC组织中ATF6阳性表达率升高、IFN-α阳性表达率下降,均与患者临床病理特征及预后密切相关。

IL-6通过激活JAK2/STAT3信号通路增强小鼠肺泡巨噬细胞的吞噬功能

目的 探讨白细胞介素6(IL-6)对MH-S小鼠肺泡巨噬细胞吞噬功能的影响及其相关机制。方法 脂多糖(LPS)经气道滴入激发构建小鼠急性肺损伤(ALI)模型,ELISA检测支气管肺泡灌洗液(BALF)中IL-6的含量。体外培养MH-S细胞,在信号转导子与转录激活子3 (STAT3)抑制剂Stattic(5μmol/L)存在与否的情况下,再加入IL-6(10 ng/mL~500 ng/mL)刺激6 h,加入荧光微球孵育2 h后,采用流式细胞术检测MH-S细胞吞噬荧光微球情况;Western blot法检测磷酸化的Janus激酶2(p-JAK2)、磷酸化的STAT3(p-STAT3)、肌动蛋白相关蛋白2(Arp2)、纤维型肌动蛋白(F-actin)的表达水平。结果 鼻腔滴入LPS后,小鼠BALF中IL-6含量显著升高。随着IL-6刺激剂量的增加,MH-S细胞吞噬荧光微球的作用增强,Arp2、 F-actin蛋白的表达水平升高。100 ng/mL IL-6刺激MH-S细胞后,p-JAK2和p-STAT3蛋白的表达水平升高。阻断MH-S细胞STAT3信号后,IL-6促进细胞吞噬的效应完全消失,IL-6诱导的Arp2、 F-actin蛋白表达增加被抑制。结论 IL-6通过激活JAK2/STAT3信号通路促进MH-S细胞Arp2、 F-actin蛋白的表达增强吞噬功能。

血清SDC-1、HDAC6、CC16水平联合检测对慢性阻塞性肺疾病患者预后不良的预测价值

目的:探讨血清多配体蛋白聚糖1(SDC-1)、组蛋白去乙酰化酶6(HDAC6)、克拉拉细胞分泌蛋白16(CC16)水平联合检测对慢性阻塞性肺疾病(COPD)患者预后不良的预测价值。方法:选取2020年11月至2023年11月该院收治的147例COPD患者进行横断面研究,设为研究组;选取同期于该院体检的147名健康者设为对照组。比较两组、不同COPD病情程度患者、不同预后COPD患者血清SDC-1、HDAC6、CC16水平;采用受试者工作特征(ROC)曲线分析入院时血清SDC-1、HDAC6、CC16水平单项及联合检测预测COPD患者预后不良的价值。结果:研究组血清SDC-1、HDAC6水平均高于对照组,血清CC16水平低于对照组,差异有统计学意义(P<0.05)。重度COPD患者血清SDC-1、HDAC6水平高于中重度、中度、轻度患者,且中重度高于中度、轻度患者,中度高于轻度患者;重度COPD患者血清CC16水平低于中重度、中度、轻度患者,且中重度低于中度、轻度患者,中度低于轻度患者,差异均有统计学意义(P<0.05)。预后不良COPD患者入院时血清SDC-1、HDAC6水平高于预后良好患者,血清CC16水平低于预后良好患者,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,入院时血清SDC-1、HDAC6、CC16水平联合检测预测COPD患者预后不良的曲线下面积(AUC)为0.938,高于三者单项检测诊断(AUC=0.774、0.771、0.716)。结论:入院时血清SDC-1、HDAC6、CC16水平联合检测预测COPD患者预后不良的价值高于三者单项检测。

间充质干细胞分泌IL-6调控巨噬细胞表型及其在炎症性疾病和肿瘤中的作用

间充质干细胞(MSCs)是一种对免疫细胞具有调控作用的成体干细胞。它可调节促炎M1型巨噬细胞向抗炎M2型巨噬细胞极化,从而发挥缓解炎症的生物学效应。在调控巨噬细胞的过程中,MSCs分泌了诸多细胞因子,其中白细胞介素-6(IL-6)发挥重要作用。一方面,IL-6通过抑制炎症进展参与炎症反应;另一方面,其通过活化M2型巨噬细胞极化的信号通路促进肿瘤侵袭转移。未来深入研究MSCs与IL-6对巨噬细胞的调控作用,有助于为炎症性疾病和恶性肿瘤的治疗提供新思路及策略。

雷帕霉素对高糖诱导的人肾小球足细胞增殖、凋亡和IL-6表达的影响及其机制

目的观察雷帕霉素对高糖诱导的人肾小球足细胞增殖、凋亡和IL-6表达的影响,并基于磷脂酰肌醇-3-激酶(PI3K)/丝氨酸-苏氨酸激酶(AKT)信号通路探讨相关机制。方法体外培养人肾小球足细胞系HGPC,分为对照组、高糖组、实验组,对照组不做干预,高糖组、实验组加入30 mmol/L D-葡萄糖,实验组在此基础上分别加入2.5、5、10μmol/L雷帕霉素,检测各组细胞活力,筛选雷帕霉素最适浓度。将HGPC细胞分为对照组、高糖组、实验组、抑制剂组、雷帕霉素+抑制剂组、雷帕霉素+激动剂组;对照组不加药物,高糖组加入30 mmol/L D-葡萄糖,抑制剂组加入30 mmol/L D-葡萄糖+10μmol/L PI3K/AKT信号通路抑制剂LY294002,实验组、雷帕霉素+抑制剂组、雷帕霉素+激动剂组加入30 mmol/L D-葡萄糖+10μmol/L雷帕霉素,雷帕霉素+抑制剂组再加入10μmol/L LY294002,雷帕霉素+激动剂组再加入10μmol/L PI3K/AKT信号通路激动剂SC79;各组给药后培养24 h。采用5-乙炔基-2’脱氧尿嘧啶核苷法检测细胞增殖能力,Hoechst 33258染色检测凋亡细胞;采用ELISA法检测细胞培养液上清中的白细胞介素6(IL-6);Western blotting法检测细胞中的细胞周期素D1(Cyclin D1)、半胱氨酸天冬氨酸蛋白酶3(Caspase-3)及PI3K/AKT通路相关蛋白。结果高糖组细胞增殖率、Cyclin D1表达低于对照组,实验组和抑制剂组细胞增殖率、Cyclin D1表达高于高糖组;与实验组相比,雷帕霉素+抑制剂组细胞增殖率、Cyclin D1表达增高,雷帕霉素+激动剂组细胞增殖率、Cyclin D1表达降低(P均<0.05)。高糖组细胞凋亡率、Caspase-3表达及p-PI3K/PI3K、p-AKT/AKT、IL-6水平高于对照组,实验组和抑制剂组细胞凋亡率、Caspase-3表达及p-PI3K/PI3K、p-AKT/AKT、IL-6水平低于高糖组;与实验组相比,雷帕霉素+抑制剂组细胞凋亡率、Caspase-3表达及p-PI3K/PI3K、p-AKT/AKT、IL-6水平下降,雷帕霉素+激动剂组凋亡率、Caspase-3表达及p-PI3K/PI3K、p-AKT/AKT、IL-6水平上升(P均<0.05)。结论雷帕霉素可促进高糖诱导的人肾小球足细胞增殖,减少细胞凋亡,减轻炎症损伤,其机制可能与抑制PI3K/AKT通路有关。