1-MCP与MT联合处理对芒果保鲜效果的影响

为探究1-甲基环丙烯(1-MCP)与褪黑素(MT)联合处理对芒果保鲜效果的影响,该研究用0.1 mg/L 1-MCP和0.2 mmol/L MT联合处理芒果后,于25℃贮藏10 d,每2 d取样测定相关指标。结果显示:1-MCP和MT联合处理可以延缓芒果果皮叶绿素降解和类胡萝卜素含量升高,在贮藏第10天,处理组的果皮叶绿素为0.078 mg/g,是对照组的5.27倍;延缓了果肉L*值的下降和a*、b*值的升高,抑制原果胶降解和可溶性果胶含量的升高,贮藏第6天处理组的原果胶含量比对照高2.53倍,而可溶性果胶含量比对照低44.04%,同时在贮藏前期显著抑制了多聚半乳糖醛酸酶(PG)和纤维素酶(Cx)活性,降低了β-半乳糖苷酶(β-Gal)活性,并且维持了果肉更完整的细胞结构,但果肉类黄酮含量在贮藏中期显著低于对照。综上,1-MCP和MT联合处理保持了芒果良好的外观品质,延缓了细胞壁物质的降解,提高了货架期品质。

Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in unresectable hepatocellular carcinoma

BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.

褪黑素通过SIRT1-BMAL1通路减轻神经病理性疼痛的机制研究

目的评价褪黑素对神经病理性疼痛夜间加重的影响,并通过特异性沉默信息调节因子1(SIRT1)-脑和肌肉ARNT样蛋白1(BMAL1)通路探讨其机制。方法96只SPF级雄性C57/B6小鼠,随机分为3组:假手术(S)组、神经病理性疼痛模型(NP)组和NP模型+褪黑素治疗(NP+M)组;术前试验小鼠置于指定光照模式环境中;采用12 h光照与12 h黑暗交替环境,持续至少两周,将自然时间转换为授时时间(ZT),光照起点定为ZT0;S组小鼠仅分离坐骨神经,NP组和NP+M组采用坐骨神经慢性缩窄性损伤制备小鼠NP模型,NP+M组术后注射10 mg/kg褪黑素;Western blot法检测术后14 d各时点脊髓的SIRT1、BMAL1和谷胱甘肽过氧化酶1(Gpx1)表达量的变化;术后通过免疫荧光技术对脊髓背角SIRT1和脊髓神经元标志物神经元特异性核蛋白(NeuN)、小胶质细胞激活标记物离子钙结合适配器分子1(iba-1)、星形胶质细胞标记物胶质纤维酸性蛋白(GFAP)进行共染色,并检测各时点iba-1以确定小胶质细胞激活状态。结果与NP组ZT10时点相比,NP组小鼠术后14 d ZT22时点SIRT1、BMAL1和Gpx1降低(P<0.05);与NP组ZT14时点相比,NP+M组ZT14时点SIRT1与BMAL1升高(P<0.05),而Gpx1于ZT18时点升高(P<0.05)。SIRT1在脊髓背角与小胶质细胞共表达;与ZT10时点相比,NP组小鼠术后14 d ZT22时点小胶质细胞表达降低(P<0.05);与ZT10时点相比,NP+M组小鼠术后14 d ZT22时点小胶质细胞表达差异无统计学意义。结论褪黑素可以减轻神经病理性疼痛夜间加重,其机制可能与激活小胶质细胞SIRT1-BMAL1通路蛋白表达有关。

筋骨痛消丸调控MLT/SIRT1介导的信号通路治疗膝骨关节炎模型大鼠的研究

目的 观察筋骨痛消丸对膝骨关节炎(Knee osteoarthritis,KOA)模型大鼠软骨组织的影响,以及软骨组织中褪黑素(MLT)、沉默信息调节因子1(SIRT1)、基质金属蛋白酶3(MMP-3)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)表达的影响,研究筋骨痛消丸治疗KOA的机制,为临床运用筋骨痛消丸治疗KOA提供实验依据及理论基础。方法 将48只SPF级SD大鼠按随机数字表法分为空白组、模型组、双醋瑞因组、筋骨痛消丸组,每组各12只。筋骨痛消丸组造模成功后给予筋骨痛消丸汤剂灌胃干预,双醋瑞因组给予双醋瑞因灌胃干预,连续干预4周,干预结束后,观察比较各组大鼠干预前后患膝关节周围肿胀度;患膝软骨组织染色,并运用ELISA、Westernblot检测法检测各组大鼠软骨组织中褪黑素(Melatonin,MLT)、沉默信息调节因子1(Sirtuin 1,SIRT1)、白细胞介素-1β(Interleukin 1β,IL-1β)、基质金属蛋白酶-3(Matrix metalloproteinase-3,MMP-3)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)含量及蛋白质表达水平。结果 采用木瓜蛋白酶关节腔内注射的造模方法成功;药物干预的两组均可以有效改善膝骨关节炎大鼠的关节肿胀度(P<0.05);与模型组比较,筋骨痛消丸组在大鼠血清中MLT、SIRT1的含量及蛋白质表达水平明显升高(P<0.05)。结论 筋骨痛消丸可以促进软骨组织中MLT、SIRT1的表达水平,并降低IL-1β、MMP-3、TNF-α的含量,其治疗KOA作用机制可能是通过激活MLT/SIRT1介导的通路,抑制下游炎症因子释放来完成的。

Argatroban promotes recovery of spinal cord injury by inhibiting the PAR1/JAK2/STAT3 signaling pathway

Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.

Melatonin Enhances Object Recognition Memory through Melatonin MT1 and MT2 Receptor-Mediated and Non-Receptor-Mediated Mechanisms in Male Mice

Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL in converting short-term memory (STM) to long-term memory (LTM) with a single administration immediately after the acquisition trial of the novel object recognition (NOR) task. These data suggest that the memory-enhancing effects of MEL may be mediated by mechanisms independent of the activation of MEL MT1 and MT2 receptors. In the present study, we examined the contribution of MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms to the acute memory-enhancing effects of MEL using NOR task. Mice were administered with either MEL, AMK, or a highly selective MT1/MT2 receptor agonist ramelteon (RAM) immediately after the acquisition trial and the effects of varying doses of these drugs on both STM and LTM performance were compared. We found that both AMK and RAM were more potent than MEL in both facilitating STM and promoting LTM formation. We also found that pretreatment with luzindole, a MT1/MT2 receptor antagonist, markedly suppressed only the effects of RAM. These results suggest that acutely administered MEL enhances NOR memory through both MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms.

连续星状神经节阻滞对颅内动脉瘤介入术后脑血管痉挛预防及对血浆褪黑素、内皮素-1的影响

目的:研究连续星状神经节阻滞(SGB)对颅内动脉瘤介入术脑血管痉挛预防及对血浆褪黑素(MT)、内皮素-1(ET-1)水平的影响。方法:选择80例颅内动脉瘤介入术病人作为研究对象,按随机数字表法均分为观察组和对照组,对照组采取全身麻醉,观察组在对照组的基础上采取连续SGB。比较2组的大脑前动脉平均血流速度(ACA-Vm)、大脑前动脉搏动指数(ACA-PI)、大脑中动脉平均血流速度(MCA-Vm)、大脑中动脉搏动指数(MCA-PI)、大脑后动脉平均血流速度(PCA-Vm)、大脑后动脉搏动指数(PCA-PI),MT、ET-1水平,术后24 h并发症。结果:对照组治疗后的ACA-Vm、ACA-PI、MCA-Vm、MCA-PI、PCA-Vm、PCA-PI均显著高于观察组(P<0.05~P<0.01)。对照组治疗后的MT显著低于观察组,ET-1显著高于观察组(P<0.05)。术后24 h,对照组并发症发生率22.50%,显著高于观察组并发症发生率7.50%(P<0.05)。结论:连续SGB可有效稳定颅内动脉瘤介入术后的脑血流,促进MT的分泌与合成,抑制ET-1增长,从而降低脑血管痉挛等并发症发生率。

Gasdermin D-mediated hepatocyte pyroptosis expands inflammatory responses that aggravate acute liver failure by upregulating monocyte chemotactic protein 1/CC chemokine receptor-2 to recruit macrophages

BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(shRNA)was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1)and its receptor CC chemokine receptor-2(CCR2)in vitro.For in vivo experiments,we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALF patients and a hepatocyte injury model increased significantly.The level of GSDMD-N protein increased most obviously(P<0.001).In vitro,downregulation of GSDMD by shRNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P<0.01).In vivo,GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P<0.001).Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1βand IL-18,GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death.However,this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF,recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses.GSDMD knockout can reduce hepatocyte death and inflammatory responses,thus alleviating ALF.

Melatonin modifies SOX2^+ cell proliferation in dentate gyrus and modulates SIRT1 and MECP2 in long-term sleep deprivation

Melatonin is a pleiotropic molecule that,after a short-term sleep deprivation,promotes the proliferation of neural stem cells in the adult hippocampus.However,this effect has not been observed in long-term sleep deprivation.The precise mechanism exerted by melatonin on the modulation of neural stem cells is not entirely elucidated,but evidence indicates that epigenetic regulators may be involved in this process.In this study,we investigated the effect of melatonin treatment during a 96-hour sleep deprivation and analyzed the expression of epigenetic modulators predicted by computational text mining and keyword clusterization.Our results showed that the administration of melatonin under sleep-deprived conditions increased the MECP2 expression and reduced the SIRT1 expression in the dentate gyrus.We observed that let-7 b,mir-132,and mir-124 were highly expressed in the dentate gyrus after melatonin administration,but they were not modified by sleep deprivation.In addition,we found more Sox2^+/5-bromo-2’-deoxyuridine(BrdU)^+cells in the subgranular zone of the sleep-deprived group treated with melatonin than in the untreated group.These findings may support the notion that melatonin modifies the expression of epigenetic mediators that,in turn,regulate the proliferation of neural progenitor cells in the adult dentate gyrus under long-term sleep-deprived conditions.All procedures performed in this study were approved by the Animal Ethics Committee of the University of Guadalajara,Mexico(approval No.CI-16610)on January 2,2016.

Melatonin attenuates cisplatin-induced HepG2 cell death via the regulation of mTOR and ERCC1 expressions

AIM:To elucidate the effects of melatonin on cisplatininduced hepatocellular carcinoma(HepG2) cell death and to identify potential cross-talk pathways.METHODS:Hepatocellular carcinoma HepG2 cells were treated with melatonin and/or cisplatin for 24 to 48 h.Cell viability and the 50% cytotoxic concentration(CC50) were calculated by MTT assays.The effects and intracellular events induced by the selected concentrations of melatonin(1 mmol/L) and cisplatin(20 μmol/L) were investigated.Cell death and survival detection were primarily evaluated using a fluorescence microscope to assess 4',6 diamideno-2-phenylindol DNA staining and acridine orange lysosome staining and then further analyzed with immunocytochemistry using an anti-LC3 antibody.The potential molecularresponses mediated by melatonin against cisplatin after the combined treatment were investigated by reverse transcription-polymerase chains reaction and Western blot analyses of the genes and proteins associated with cell survival and death.A cell cycle analysis was performed using a flow cytometry assay.RESULTS:Melatonin had a concentration-dependent effect on HepG2 cell viability.At 1 mmol/L,melatonin significantly increased the cell viability percentage and decreased reactive oxygen species production due to cisplatin.Melatonin reduced cisplatin-induced cell death,decreasing phosphorylated p53 apoptotic protein,cleaved caspase 3 and Bax levels but increasing anti-apoptotic Bcl-2 gene and protein expression.When combined with cisplatin,melatonin induced S phase(DNA synthesis) cell cycle arrest and promoted autophagic events in HepG2 cells.Melatonin also had a concentration-dependent effect on Beclin-1 and its autophagic regulator mammalian target of rapamycin(mTOR) as well as the DNA excision repair cross complementary 1(ERCC1) protein.The expression levels of these proteins were altered in HepG2 cells during cisplatin or melatonin treatment alone.In the combination treatment,melatonin reversed the effects of cisplatin by suppressing the over-expression of mTOR and ERCC 1 and enhancing the expression levels of Beclin-1 and microtubule-associated protein-light chain3-Ⅱ,leading to intracellular autophagosome progression.CONCLUSION:Melatonin attenuated cisplatin-induced cell death in HepG2 cells via a counter-balance between the roles of apoptotic- and autophagy-related proteins.

采前褪黑素和1-MCP处理对百香果采后贮藏品质的影响

为了探究采前褪黑素和1-MCP处理对百香果采后保鲜效果的影响,以台农一号百香果为试材,研究采前喷施200μmol/L褪黑素、5.0μg/L 1-MCP、200μmol/L褪黑素+5.0μg/L 1-MCP和清水(对照)对百香果贮藏期果实生理和营养品质的影响,为百香果采后保鲜技术的研发提供理论依据。结果表明,与对照相比,采前褪黑素和1-MCP处理均可以显著抑制百香果贮藏后期果实失重率、皱缩指数、果皮MDA含量和果皮相对电导率的增加,延缓好果率、果皮含水量和果实硬度的降低,有效保持果实可溶性固形物、可滴定酸、维生素C、可溶性蛋白含量,提高果实SOD和CAT等抗氧化酶活性。综上,采前褪黑素和1-MCP处理均可以明显延缓百香果贮藏期间果实的衰老,有效保持果实的贮藏品质,其中,褪黑素和1-MCP复合处理的效果要好于单一处理,且保鲜效果最佳。

Melatonin Ameliorates Liver Fibrosis Induced by Carbon Tetrachloride in Rats via Inhibiting TGF-β1/Smad Signaling Pathway

Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect. Nevertheless, the mechanism is not completely identified. This study was conducted to investigate the effects of melatonin on TGF-β1/Smad signaling pathway in liver fibrosis in rats. The liver fibrosis model was made by the subcutaneous injection of CC14. The liver pathology changes were detected using hematoxylin and eosin （H＆E） staining and Van Gieson （VG） staining. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities were measured with an autoanalyzer. Glutathione peroxidase （GPx） activities and levels of malondialdehyde （MDA） and hydroxyproline （Hyp） in liver were evaluated by spectrophotometry. Expression levels of TGF-β1, Smad2/3, phosphorylated Smad2/3 （p-Smad2/3） and Smad7 in liver were detected by immunohistochemistry and Western blot analysis. Results showed that melatonin suppressed CC14-induced liver fibrosis, along with an improvement in histological changes, significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver. Melatonin improved liver function indicated by decreased serum ALT and AST activities. In addition, melatonin exerted its anti-oxidant effects, as supported by decreased MDA levels and increased GPx activities in liver. Furthermore, melatonin inhibited TGF-β1/Smad pathway, as evidenced by decreased TGF-β1, Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver. In conclusion, melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-β1/Smad pathway. It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.

Basic Fibroblast Growth Factor and Fibroblast Growth Factor Receptor-1 in Human Meningiomas

The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features and angiogenesis were investigated by means of immunohistochemical technique. The expression of bFGF and FGFR-1 was detected by antibody of bFGF or FGFR-1. The tumors' angiogenesis was evaluated by microvascular density (MVD) and, which was observed by use of CD34-antibody immunohistochemically. The results showed that there were varied degrees of the expression of bFGF and FGFR-1 proteins in meningiomas. The expression was correlated with the tumors' histological characters and angiogenesis. It was concluded that bFGF and FGFR-1 might play important roles in meningiomas' angiogenesis and proliferation. The expression positive rate of bFGF and FGFR-1 may provide an indication of evaluating the histological and malignant degree of the tumor.

Sleeve gastrectomy prevents lipoprotein receptor-1 expression in aortas of obese rats

AIM: To investigate the effects of sleeve gastrectomy on adipose tissue infiltration and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in rat aortas. METHODS: Twenty-four rats were randomized into three groups: normal chow (control), high fat diet (HD) and high fat diet with sleeve gastrectomy (SG). After surgery, the HD and SG groups were fed a high fat diet. Animals were sacrificed and plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) levels were determined. LOX-1 protein and LOX-1 mRNA expression was also measured. Aortas were stained with Nile red to visualize adipose tissue. RESULT: Body weights were higher in the HD group compared to the other groups. HDL levels in control,HD, and SG groups were 32.9 ± 6.2 mg/dL, 43.4 ± 4.0 mg/dL and 37.5 ± 4.3 mg/dL, respectively. LDL levels in control, HD, and SG groups were 31.8 ± 4.5 mg/dL, 53.3 ± 5.1 mg/dL and 40.5 ± 3.7 mg/dL, respectively. LOX-1 protein and LOX-1 mRNA expression was greater in the HD group versus the other groups. Staining for adipose tissue in aortas was greater in the HD group in comparison to the other groups. Thus, a high fat diet elevates LOX-1 protein and mRNA expression in aorta. CONCLUSION: Sleeve gastrectomy decreases plasma LDL levels, and downregulates LOX-1 protein and mRNA expression.

Significance of 125I radioactive seed implantation on growth differentiation factor and programmed death receptor-1 during treatment of oral cancer

BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and chemotherapy;but recently,more and more studies have shown that the stress trauma caused by surgery and the side effects of radiotherapy and chemotherapy seriously affect the prognosis of patients.AIM To determine the significance of 125I radioactive seed implantation on growth differentiation factor 11(GDF11)and programmed death receptor-1(PD-1)during treatment of OC.METHODS A total of 184 OC patients admitted to The Second Affiliated Hospital of Jiamusi University from May 2015 to May 2017 were selected as the research subjects for prospective analysis.Of these patients,89 who received 125I radioactive seed implantation therapy were regarded as the research group(RG)and 95 patients who received surgical treatment were regarded as the control group(CG).The clinical efficacy,incidence of adverse reactions and changes in GDF11 and PD-1 before treatment(T0),2 wk after treatment(T1),4 wk after treatment(T2)and 6 wk after treatment(T3)were compared between the two groups.RESULTS The efficacy and recurrence rate in the RG were better than those in the CG(P<0.05),while the incidence of adverse reactions and survival rate were not different.There was no difference in GDF11 and PD-1 between the two groups at T0 and T1,but these factors were lower in the RG than in the CG at T2 and T3(P<0.05).Using receiver operating characteristic(ROC)curve analysis,GDF11 and PD-1 had good predictive value for efficacy and recurrence(P<0.001).CONCLUSION 125I radioactive seed implantation has clinical efficacy and can reduce the recurrence rate in patients with OC.This therapy has marked potential in clinical application.The detection of GDF11 and PD-1 in patients during treatment showed good predictive value for treatment efficacy and recurrence in OC patients,and may be potential targets for future OC treatment.

褪黑素受体Mel 1a在皖西白鹅各组织中的表达与分布

【目的】探究褪黑素受体Mel 1a在皖西白鹅各组织中的分布特点和表达水平,为褪黑素在皖西白鹅的功能调控奠定理论基础。【方法】以皖西白鹅作为研究对象,提取各组织器官的总RNA,采用Real-time PCR和Western blot检测褪黑素受体Mel 1a mRNA和蛋白在鹅组织中的分布和差异性表达,免疫组化检测褪黑素受体Mel 1a蛋白在鹅的组织中的表达。【结果】在心脏、肝脏、脾脏、肺脏、肾脏、胰脏、大脑、小脑、肌肉、卵巢各组织中均存在Mel 1a mRNA表达;Mel 1a蛋白广泛分布于大脑、心脏、肾脏、肝脏、肺脏、脾脏、胰脏和肌肉组织细胞中,利用Image-pro plus 6软件分析免疫组化阳性信号的IOD值显示,脾脏阳性信号最强,其次是胰腺。脾脏显著强于大脑,肺脏中的信号显著强于心脏和肌肉组织。采用Real time PCR和Western blot技术检测各组织中Mel 1a mRNA和蛋白表达水平,结果表明,卵巢中表达水平最高,其次是胰腺、脾脏、肾脏、肝脏、心脏和脑组织中,肺脏和肌肉中的表达水平最低,另外在各级卵泡中Mel 1a mRNA的表达水平随卵泡发育逐渐增加,直到卵泡发育到直径超过3 cm后,其表达量下降。【结论】皖西白鹅各组织中均存在褪黑素受体,其中在卵巢中表达最高,褪黑素可通过受体介导调控皖西白鹅多种生物功能,尤其是对皖西白鹅卵泡发育的调控。

Expression of triggering receptor-1 in myeloid cells of mice with acute lung injury

BACKGROUND： Myeloid cell （TREM-1） is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury （ALl） by intraperitoneal injection of lipopolysaccharide （LPS） was established to observe the expression pattern of TREM-1 in lung tissue and the role of TREM-1 in pulmonary inflammatory response to ALl.METHODS： Thirty BALB/C mice were randomly divided into a normal control group （n=6） and an ALl group （n=24）. The model of ALl was made by intraperitonal injection of LPS in dose of 10 mg/ kg. Specimens from peripheral blood and lung tissue were collected 6, 12, 24 and 48 hours after LPS injection. RT-PCR was used to detect TREM-1 mRNA, and ELISA was employed for detection of TREM-1 protein and TNF-a protein, and HE staining was performed for the pathological Smith lung scoring under a light microscope.RESULTS： The expressions of TREM-1 mRNAin lung tissue and blood of the ALl group 6, 12, 24, and 48 hours after injection of LPS were higher than those in the control group. The levels of TREM- 1 protein and the levels of TNF-a protein in lung tissue of the ALl group 6, 12, 24, and 48 hours after LPS injection were higher than those of the control group; the level of TREM-1 protein peaked 12 hours after LPS injection, but it was not significantly correlated with the expression of TREM-1 mRNA （P=0.14）; the TNF-a concentration was positively correlated with TREM-1 levels in lung tissue and with Smith pathological score （r=0.795, P=0.001 ：r=0.499, P=0.034）, but not with the expression of TREM-1 mRNA （P=0.176）.CONCLUSION： The expression of TREM-1 mRNA in lung tissue of mice with ALl is elevated, and the expression of TREM-1 mRNA is related to the level of TNF-a and the severity of inflammatory response to ALl. The expressions of the TREM-1 gene are not consistent with the levels of TREM-1 protein, suggesting a new functional protein involved in immune regulation.

LOTUS, a potent blocker of Nogo receptor-1 causing inhibition of axonal growth

Glia-derived axonal growth inhibitory proteins limit functional repair following damage to the adult cen- tral nervous system （CNS）. Nogo proteins, myelin-as- sociated glycoprotein （MAG）, oligodendrocyte myelin glycoprotein （OMgp） and B lymphocyte stimulator （BLyS）, are 4 inhibitors that commonly interact with the neuronal receptor, Nogo receptor-1 （NgR1）, lead- ing to inhibition of axonal growth. Here, we demon- strate that lateral olfactory tract usher substance （LOTUS） binds to NgR1 and blocks the binding of all four ligands to NgR1, resulting in the suppression of axonal growth inhibition induced by these NgR1 li- gands. LOTUS allows neurons to overcome NgRl-me- diated axonal growth inhibition, raising the possibility that LOTUS may be useful in future therapeutic ap- proaches as an endogenous potent inhibitor of NgR1 for promoting neuronal regeneration.

Plasma and cerebrospinal fluid interleukin-1β during lipopolysaccharide-induced systemic inflammation in ewes implanted or not with slow-release melatonin

Background： Interleukin-1β（IL-1β） is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cerebrospinal fluid（CSF） is peripheral circulation, while over time, cytokines produced in the brain are more important. Melatonin has been shown to decrease pro-inflammatory cytokines concentration in the brain. In ewes, melatonin is used to advance the onset of a breading season. Little is known about CSF concentration of IL-1β in ewes and its correlation with plasma during inflammation as well as melatonin action on the concentration of IL-1β in blood plasma and the CSF, and brain barriers permeability in early stage of lipopolysaccharide（LPS）-induced inflammation.Methods： Systemic inflammation was induced through LPS administration in melatonin-and sham-implanted ewes. Blood and CSF samples were collected before and after LPS administration and IL-1β and albumin concentration were measured. To assess the functions of brain barriers albumin quotient（QAlb） was used.Expression of IL-1β（Il1B） and its receptor type Ⅰ（Il1r1） and type Ⅱ（Il1r2） and matrix metalloproteinase（Mmp） 3 and 9 was evaluated in the choroid plexus（CP）.Results： Before LPS administration, IL-1β was on the level of 62.0 ± 29.7 pg/mL and 66.4 ± 32.1 pg/mL in plasma and 26.2 ± 5.4 pg/mL and 21.3 ± 8.7 pg/mL in the CSF in sham-and melatonin-implanted group, respectively.Following LPS it increased to 159.3 ± 53.1 pg/mL and 197.8 ± 42.8 pg/mL in plasma and 129.8 ± 54.2 pg/mL and139.6 ± 51.5 pg/mL in the CSF. No correlations was found between plasma and CSF IL-1β concentration after LPS in both groups. The QAlb calculated before LPS and 6 h after was similar in all groups. Melatonin did not affected m RNA expression of Il1B, Il1r1 and Il1r2 in the CP. The m RNA expression of Mmp3 and Mmp9 was not detected.Conclusions： The lack of correlation between plasma and CSF IL-1β concentration indicates that at the beginning of inflammation the local synthesis of IL-1β in the CP is an important source of IL-1β in the CSF. Melatonin from slow-release implants does not affect IL-1β concentration in plasma and CSF in early stage of systemic inflammation.

Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 protein in the hippocampus in rats exhibiting chronic stress-induced depression

There is evidence that the expression of members of the fibroblast growth factor （FGF） protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 （FGF2） and fibroblast growth factor receptor-1 （FGFR1） protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression.