P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

Phosphotungstic acid immobilized on amino-functionalized TS-1 zeolite as a solid acid catalyst for the synthesis of tributyl citrate

The amino-functionalization of TS-1 zeolite followed by immobilization of phosphotungstic acid(HPW)was presented to prepare a strong solid acid catalyst for the synthesis of bio-based tributyl citrate from the esterification of citric acid and n-butanol.γ-Aminopropyltriethoxysilane(APTES)was first grafted on the TS-1 zeolite via the condensation reactions with surface hydroxyl groups,and subsequently the HPW was immobilized via the reaction between the amino groups and the protons from HPW-forming strong ionic bonding.The Keggin structure of HPW and MFI topology of TS-1 zeolite were well maintained after the modifications.The amino-functionalization generated abundant uniformly distributed active sites on TS-1 for HPW immobilization,which promoted the dispersity,abundance,as well as the stability of the acid sites.The tetrahedrally coordinated framework titanium and non-framework titania behaved as weak Lewis acid sites,and the protons from the immobilized HPW acted as the moderate or strong Brønsted acid sites.An optimized TBC yield of 96.2%(mol)with a conversion of-COOH of 98.1%(mol)was achieved at 150℃for 6 h over the HPW immobilized on amino-functionalized TS-1.The catalyst exhibited good stability after four consecutive reaction runs,where the activity leveled off at still a relatively high level after somewhat deactivation possibly caused by the leaching of a small portion of weakly anchored APTES or HPW.

Ganoderic acid A ameliorates renalfibrosis by suppressing the expression of NPC1L1

Objective: The study aimed to explore the protective mechanism of Ganoderic acid A (GAA) in renal fibrosisand to verify that GAA can ameliorate renal fibrosis by regulating the Niemann-pick C1-like 1 (NPC1L1) gene. Methods:Transforming growth factor beta1 (TGF-β1) was used to treat Human Kidney-2 (HK-2) cells to establish a renal fibrosismodel. The differentially expressed genes in the control (CTRL) group, TGF-β1 group, and TGF-β1 + GAA group werescreened via transcriptome sequencing technology and verified by qPCR and Western blot experiments. The NPC1L1gene overexpression plasmid was constructed. The expression levels of N-cad, E-cad, and Slug-related proteins inCTRL, TGF-β1, TGF-β1+GAA (25 μg/mL), and TGF-β1+GAA (25 μg/mL) + NPC1L1 Overexpression (OE) groupswere detected by qPCR and Western blot analysis. Western blot analysis was used to identify the extracellular matrixassociated proteins Tenascin-C, α-SMA, and fibrosis-related protein Collagen I. Fibrosis marker protein Fibronectinwas detected and quantified by immunofluorescence. Results: Transcriptomic sequencing revealed that TGF-β1stimulation led to 267 differentially regulated genes, with 118 up-regulated and 149 down-regulated, while furthermodulation of 213 genes, comprising 112 up-regulated and 101 down-regulated genes, was observed in the GAAintervention group. The target gene in these processes was found to be NPC1L1 by investigations using GeneOntology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). qPCR and Western blot resultsconfirmed that TGF-β1 increased NPC1L1 expression, which was attenuated by GAA. Additionally, TGF-β1upregulated N-cad and Slug. However, GAA reversed this effect and NPC1L1 overexpression partially rescued theGAA effect. TGF-β1 also decreased E-cad expression, reversed by GAA, and NPC1L1 overexpression antagonized thisreversal. Furthermore, TGF-β1 promoted Collagen I, α-SMA, and Tenascin-C expression, and GAA reduced theselevels, effects that were reversed by NPC1L1 overexpression. Immunofluorescence results showed that TGF-β1increased fibronectin expression, which was decreased by GAA, and increased by NPC1L1 overexpression.Conclusion: GAA ameliorates renal fibrosis by antagonizing NPC1L1 gene expression inhibiting epithelialmesenchymal transition and reducing extracellular matrix formation.

Glycyrrhizic acid alleviates lung injury in sepsis through SIRT1/HMGB1 pathway

Objectives:This study explores the protective effects of glycyrrhizic acid(GA)on sepsis-induced cellular damage and inflammation in acute lung injury(ALI),specifically through the modulation of the sirtuin 1(SIRT1)and high mobility group box 1(HMGB1)pathway.Methods:The study employed two experimental models:lipopolysaccharide(LPS)-induced BEAS-2B human lung epithelial cells and cecal ligation and puncture(CLP)rats,to simulate sepsis conditions.The cell model involved treatments with LPS,GA,control siRNA(si-NC),and SIRT1-specific siRNA(si-SIRT1).Evaluations included cell viability,apoptosis,and cytokine production.In the rat model,treatments included GA and the SIRT1 inhibitor EX527,with assessments on lung tissue damage,inflammation,and protein expression using Western blot and co-immunoprecipitation(Co-IP)analysis.Results:LPS exposure significantly reduced SIRT1 mRNA levels and cell viability in BEAS-2B cells,which effects were reversed by cotreatment with GA and si-NC but negated by si-SIRT1.LPS also induced apoptosis and increased pro-inflammatory cytokines and HMGB1 expression,which were mitigated by GA and si-NC and exacerbated by si-SIRT1.In CLP rats,GA treatment decreased lung tissue damage,inflammatory cytokines,and HMGB1 expression,and enhanced SIRT1 levels.However,these protective effects were reversed when GA was combined with EX527.Conclusion:GA demonstrates significant protective effects against LPS-induced damage and inflammation in lung cells and tissue by modulating the SIRT1-HMGB1 pathway.This suggests that GA could be a potential therapeutic strategy for treating sepsis and related inflammatory conditions.

Overexpression of PbrGA2ox1 enhances pear drought tolerance through the regulation of GA_(3)-inhibited reactive oxygen species detoxification and abscisic acid signaling

Drought stress is a devastating natural disaster driven by the continuing intensification of global warming,which seriously threatens the productivity and quality of several horticultural crops,including pear.Gibberellins(GAs)play crucial roles in plant growth,development,and responses to drought stress.Previous studies have shown significant reductions of GA levels in plants under drought stress;however,our understanding of the intrinsic regulation mechanisms of GA-mediated drought stress in pear remains very limited.Here,we show that drought stress can impair the accumulation of bioactive GAs(BGAs),and subsequently identified PbrGA2ox1 as a chloroplast-localized GA deactivation gene.This gene was significantly induced by drought stress and abscisic acid(ABA)treatment,but was suppressed by GA_(3)treatment.PbrGA2ox1-overexpressing transgenic tobacco plants(Nicotiana benthamiana)exhibited enhanced tolerance to dehydration and drought stresses,whereas knock-down of PbrGA2ox1 in pear(Pyrus betulaefolia)by virus-induced gene silencing led to elevated drought sensitivity.Transgenic plants were hypersensitive to ABA,and had a lower BGAs content,enhanced reactive oxygen species(ROS)scavenging ability,and augmented ABA accumulation and signaling under drought stress compared to wild-type plants.However,the opposite effects were observed with PbrGA2ox1 silencing in pear.Moreover,exogenous GA_(3)treatment aggravated the ROS toxic effect and restrained ABA synthesis and signaling,resulting in the compromised drought tolerance of pear.In summary,our results shed light on the mechanism by which BGAs are eliminated in pear leaves under drought stress,providing further insights into the mechanism regulating the effects of GA on the drought tolerance of plants.

FaSnRK1a mediates salicylic acid pathways to enhance strawberry resistance to Botrytis cinerea

Strawberry is a major fruit crop worldwide because its nutritional and health benefits to human health,but its productivity is limited by Botrytis cinerea.Sucrose nonfermentation 1-related protein kinase 1(SnRK1)has a defense function against pathogens,but the function of SnRK1 in the defense response to B.cinerea in plants is still unclear.In this study,FaSnRK1a-OE and RNAi fruits were constructed and then inoculated with B.cinerea.The result reveals a positive role of Fa SnRK1a in the regulation of resistance to gray mold.FaSnRK1a affects SA content by regulating FaPAL1 and FaPAL2 expressions.The genes related to the SA signaling pathway(FaTGA1 and FaTGA2.1)were significantly increased/decreased in FaSnRK1a-OE or FaSnRK1a-RNAi fruit,respectively.FaSnRK1a interacted with the FaWRKY33.2 protein and negatively regulated FaWRKY33.2 expression,and FaWRKY33.2 acts as a repressor of disease resistance to B.cinerea.Finally,FaSnRK1a regulates the expression of six PR genes and the activities of antioxidant enzymes to boost defense response after B.cinerea inoculation.Our findings showed that FaSnRK1a increases the resistance of strawberry fruit to B.cinerea via SA signaling pathway and interaction with the FaWRKY33.2 transcription factor.

Mepiquat chloride increases the Cry1Ac protein content of Bt cotton under high temperature and drought stress by regulating carbon and amino acid metabolism

The effects of mepiquat chloride(DPC)on the Cry1Ac protein content in Bacillus thuringiensis(Bt)cotton boll shells under high temperature and drought stress were investigated to provide a theoretical reference for Bt cotton breeding and high-yield and-efficiency cotton cultivation.This study was conducted using Bt cotton cultivar‘Sikang 3'during the 2020 and 2021 growing seasons at Yangzhou University Farm,Yangzhou,Jiangsu Province,China.Potted cotton plants were exposed to high temperature and drought stress,and sprayed with either 20 mg L^(-1)DPC or water(CK).Seven days after treatment,the Cry1Ac protein content,α-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content were measured,and transcriptome sequencing was performed.DESeq was used for differential gene analysis.Under the DPC treatment,the Cry1Ac protein content increased by 4.7-11.9% compared to CK.Theα-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content all increased.Transcriptome analysis revealed 7,542 upregulated genes and 10,449 downregulated genes for DPC vs.CK.Gene ontology(GO)and Kyoto Encyclopedia of Gene and Genomes(KEGG)analyses showed that the differentially expressed genes were mainly involved in biological processes,such as carbon and amino acid metabolism.For example,genes encoding 6-phosphofructokinase,pyruvate kinase,glutamic pyruvate transaminase,pyruvate dehydrogenase,citrate synthase,isocitrate dehydrogenase,2-oxoglutarate dehydrogenase,glutamate synthase,1-pyrroline-5-carboxylate dehydrogenase,glutamic oxaloacetic transaminase,amino-acid N-acetyltransferase,and acetylornithine deacetylase were all significantly upregulated.The DPC treatment increased pyruvate,α-ketoglutarate,and oxaloacetate by increasing the operational rate of the glycolytic pathway of the citric acid cycle.It also significantly upregulated the genes encoding glutamate synthase,pyrrolidine-5-carboxylic acid dehydrogenase,glutamate oxaloacetate transaminase,and N-acetylglutamate synthetase,while it downregulated the genes encoding glutamine synthetase.Therefore,the synthesis of aspartic acid,glutamic acid,pyruvate,and arginine increased after treatment with DPC,and the Cry1Ac protein content was increased by regulating carbon and amino acid metabolism.

Ferulic acid reduces inflammatory response induced by radiation through Sirt1-NLRP3 pathway

Objective:A model of inflammatory damage was induced by radiation to investigate whether ferulic acid(FA)can reduce the inflammatory response through the Sirt1-NLRP3 inflammatory pathway.This will help discover radiation-protective drugs and elucidate the molecular mechanisms related to radiation-induced inflammatory damage.Methods:A mouse model of radiation-induced immunoinflammatory injury was established to verify the anti-inflammatory effects of FA in vivo.C57BL/6J mice were randomly divided into six groups,and 5 Gy whole-body irradiation was used for modeling.Mice were administered a gastric solvent,amifostine,or 25,50,or 100 mg/kg FA daily for 12 days,consecutively,before irradiation.The serum of mice was collected 24 hour after irradiation to observe the content of inflammatory factors interleukin(IL)-1β,IL-18,IL-6,and tumor necrosis factor(TNF)-α.The spleen and thymus tissues of mice were weighed and the organ index was calculated for pathological testing and immunofluorescence detection.Results:FA reduced the radiation-induced decrease in the spleen and thymus indices.FA significantly reduced the secretion of inflammatory factors in the serum and reversed the radiation-induced reduction in lymphocytes in the spleen and thymus of mice.FA activated Sirt1 and inhibited the expression of the NLRP3 inflammasome to alleviate the inflammatory response.Conclusions:FA reduced radiation-induced inflammation in animals,possibly by activating Sirt1 and reducing nucleotide oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome expression,thereby reducing the secretion of inflammatory factors.

Targeting CXCR4 and EDN1 for the treatment of recurrent miscarriage using stearic acid from traditional Chinese medicine

Background:Recurrent miscarriage(RM)affects an estimated 1-3%of couples attempting to conceive,and its molecular components stay ineffectively caught on.This study aims to explore potential therapeutic targets for RM by examining gene expression patterns and biological pathways in both mouse and human RM models.Meanwhile,explore relevant traditional Chinese medicine(TCM)components targeting potential therapeutic targets.Methods:We utilized the GSE211251 mouse and the GSE26787 human datasets,employing gene set enrichment analysis and gene metaphysics analysis to examine differentially expressed genes and enriched pathways.Single-cell RNA analysis uncovered cellular heterogeneity and arranged pharmacology-mapped potential drug-target intelligence.We employed molecular docking strategies to assess the affinity of TCM components for key proteins.Results:In the mouse model,genes such as Ly6f1 and Gpr26 were upregulated,while Stc5a and Galca exhibited downregulation.Gene set enrichment analysis identified key pathways,including the tumor necrosis factor-mediated signaling pathway.In human samples,Gene Ontology analysis highlighted processes such as apoptosis and cell adhesion.Single-cell RNA analysis revealed distinct cellular populations between normal and RM samples.Systems pharmacology identified C-X-C motif chemokine receptor 4(CXCR4)and endothelin 1(EDN1)as potential key targets,and molecular docking confirmed that stearic acid from TCM appears to regulate these proteins.Conclusion:This study presents a comprehensive analysis of the genetic and cellular underpinnings of RM,identifying CXCR4 and EDN1 as promising therapeutic targets.Stearic acid from TCM could provide targeted treatment by modulating these key proteins,paving the way for new RM treatment strategies.

Pachymic acid exerts antitumor activities by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B

Objective:To determine the inhibitory effects of pachymic acid on lung adenocarcinoma(LUAD)cells and elucidate its underlying mechanism.Methods:CCK-8,wound healing,Transwell,Western blot,tube formation,and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation,metastasis,angiogenesis as well as autophagy.Subsequently,molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B(PTP1B).Moreover,PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid.Results:Pachymic acid suppressed LUAD cell viability,metastasis as well as angiogenesis while inducing cell autophagy.It also targeted PTP1B and lowered PTP1B expression.However,PTP1B overexpression reversed the effects of pachymic acid on metastasis,angiogenesis,and autophagy as well as the expression of Wnt3a andβ-catenin in LUAD cells.Conclusions:Pachymic acid inhibits metastasis and angiogenesis,and promotes autophagy in LUAD cells by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B.

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.

1-甲基环丙烯结合水杨酸处理维持百香果甲基环丙烯结合水杨酸处理维持百香果果实贮藏品质

为延长百香果的贮藏期并保持贮藏过程中的品质,对比研究2 mmol/L水杨酸(salicylic acid,SA)、1 mmol/L 1-甲基环丙烯(1-methylcyclopropene,1-MCP)、1-MCP结合SA处理对紫色百香果果实采后贮藏期间品质、活性氧、抗氧化酶指标的影响。百香果果实经SA、1-MCP和1-MCP结合SA处理后,一定程度抑制乙烯的释放和脂氧合酶(li-poxygenase,LOX)活性,促进几丁质酶(chitinase,CHI)和β-1,3-葡聚糖酶(β-1,3-glucanase,GLU)的活性,增强抗氧化和抗病性作用,降低腐烂率。但因SA可以增强呼吸,故导致凹陷和失重,加快总酸流失;1-MCP抑制呼吸作用,增强超氧化物歧化酶(superoxide dismutase,SOD)活性,有利于控制失重和凹陷,但其对过氧化物酶(peroxidase,POD)活性的影响不利于控制衰老。1-MCP结合SA对POD活性,CHI活性以及GLU活性的正向影响强于单独使用1-MCP或SA处理。因此,1-MCP结合SA通过提高百香果果实的抗氧化能力和抗病能力,降低百香果果实的凹陷、失重和腐烂率,且可有效避免单独使用1-MCP或SA处理的不良作用,协同维持百香果果实采后贮藏品质。

脓毒症患者连续性血液净化治疗前后PCT Trx-1D-Lac表达及意义

目的:探讨脓毒症患者连续性血液净化(CBP)治疗前后血清降钙素原(PCT)、硫氧还蛋白-1(Trx-1)、D-乳酸(D-Lac)水平变化,分析其对CBP疗效的预测价值及临床意义。方法:选取2021年1月至2022年12月本院100例脓毒症患者作为观察组,另遵循1∶1配对原则,选取100例健康体检者作为对照组。统计两组血清PCT、Trx-1、D-Lac水平。观察组接受CBP治疗,依据治疗效果分为存活亚组、死亡亚组。比较不同亚组血清PCT、Trx-1、D-Lac水平、急性生理学与慢性健康状况Ⅱ评分(APACHEⅡ)及治疗前后其变化差值。Pearson分析各血清指标水平变化差值与APACHEⅡ评分相关性。采用受试者工作特征曲线(ROC)及曲线下面积(AUC)分析各血清指标水平变化差值对疗效的预测价值。采用卡普兰-迈耶(Kaplan-Meier)分析不同血清表达者28d内生存状况。结果:观察组血清PCT、Trx-1、D-Lac水平高于对照组(P<0.05);治疗1周后,死亡亚组血清PCT、Trx-1、D-Lac水平及APACHEⅡ评分高于存活亚组,且变化差值小于存活亚组(P<0.05);各血清指标水平变化差值与APACHEⅡ评分呈正相关(P<0.05);各血清指标水平变化差值联合预测CBP疗效的AUC分别大于单一指标预测、各血清指标联合预测(P<0.05);PCT、Trx-1、D-Lac水平变化差值高表达者死亡风险分别是低表达的4.828、3.600、2.318倍,且生存率高于低表达者(P<0.05)。结论:脓毒症患者CBP治疗前后血清PCT、Trx-1、D-Lac水平变化可反映病情严重程度,且与28d内生存情况密切相关,联合检测其变化差值对CBP疗效具有一定预测价值。

COPD急性加重期患者外周血单个核细胞SOCS-1、TLR4 mRNA及血清cTnT、尿酸水平变化分析

目的探讨慢性阻塞性肺疾病(COPD)急性加重期患者外周血单个核细胞中细胞因子信号抑制蛋白-1(SOCS-1)、Toll样受体4(TLR4)mRNA水平及血清心肌肌钙蛋白T(cTnT)、尿酸水平变化。方法收集COPD急性加重期(组)患者70例,COPD稳定期(组)患者40例,对照组健康志愿者40名。检测外周血单个核细胞SOCS-1、TLR4 mRNA水平及血清cTnT、尿酸浓度;行肺功能检查并记录相关指标(FEV1、FEV1%、FEV1/FVC%)。对COPD急性加重期患者进行1 a随访,分为预后不良组和预后良好组。对外周血单个核细胞SOCS-1、TLR4 mRNA水平、血清cTnT、尿酸浓度行Pearson相关性分析,并对COPD急性加重期患者预后评估价值进行ROC曲线分析。结果COPD急性加重期组SOCS-1 mRNA表达水平明显低于COPD稳定期组、对照组,TLR4 mRNA水平及血清cTnT、尿酸浓度明显高于COPD稳定期组和对照组(均P<0.01)。COPD急性加重期组FEV1、FEV1%、FEV1/FVC%明显低于COPD稳定期组和对照组(P<0.05)。COPD急性加重期患者FEV1/FVC%与外周血单个核细胞SOCS-1 mRNA表达水平呈正相关关系(P<0.01),与外周血单个核细胞TLR4 mRNA水平及血清cTnT、尿酸浓度呈负相关关系(P<0.01)。预后不良组SOCS-1 mRNA水平明显低于预后良好组,TLR4 mRNA水平及血清cTnT、尿酸浓度明显高于预后良好组(P<0.05)。外周血单个核细胞SOCS-1、TLR4 mRNA水平及血清cTnT、尿酸联合检测对COPD急性加重期患者预后具有较高的评估价值。结论COPD急性加重期患者SOCS-1低表达,TLR4、cTnT、尿酸高表达,且与肺功能水平密切相关,联合检测对患者预后具有较高的评估价值。

阿江榄仁酸由AMPK/mTOR/HO-1信号通路调控自噬对糖尿病视网膜病变影响

目的探讨阿江榄仁酸(arjunolic acid,AA)对糖尿病视网膜病变(diabetic retinopathy,DR)大鼠视网膜细胞自噬及AMPK/mTOR/HO-1信号通路的影响。方法以健康SD大鼠为研究对象,构建链脲佐菌素(STZ)诱导的糖尿病大鼠模型,随机分为对照组(Con)组、模型(STZ)组、AA低剂量(AAL,10 mg/kg)组和AA高剂量(AAH,10 mg/kg)组。连续给药10周后,HE染色检测视网膜组织病理结构;qRT-PCR检测视网膜组织白介素(IL)-1β、IL-6和线粒体丙酮酸转运载体(MPC)-1的mRNA表达;二氢乙锭(DHE)染色评估视网膜组织ROS产生;Western blot检测自噬和AMPK/mTOR/HO-1信号通路相关蛋白表达。结果与Con组比较,STZ组大鼠视网膜出现肿胀和空泡样变化等病理变化,中央视网膜ONL层厚度和细胞核计数明显降低(P<0.01);IL-1β、IL-6和MCP-1的mRNA水平显著增高(P<0.05);视网膜外核层(ONL)、内核层(INL)和神经节细胞层(GCL)中ROS产生增加(P<0.01);LC3II/I比率、HO-1和p-AMPK/AMPK蛋白表达显著降低,p62和p-mTOR/mTOR表达升高(P<0.01)。与STZ组比较,AAL和AAH组大鼠视网膜ONL厚度和细胞核计数逐渐升高,结构相对规整(P<0.05);AAH组IL-1β、IL-6和MCP-1的mRNA表达明显降低(P<0.05);视网膜ONL、INL和GCL中ROS产生逐渐降低(P<0.01);LC3II/I比率、p-AMPK/AMPK和HO-1表达逐渐升高,p62和p-mTOR/mTOR表达逐渐降低(P<0.01)。结论阿江榄仁酸可能是治疗DR的候选药物,可能机制为通过AMPK/mTOR/HO-1调节的自噬途径保护视网膜细胞免受STZ诱导的氧化应激和炎症损伤。

孕妇血清可溶性血管内皮生长因子受体-1、叶酸水平与慢性胎儿宫内窘迫的相关性分析

目的分析孕妇血清可溶性血管内皮生长因子受体-1(sFlt-1)、叶酸水平与慢性胎儿宫内窘迫的相关性。方法选取2023年6月—2023年12月南通市妇幼保健院接收的103例孕妇。将出现胎儿慢性宫内窘迫的48例孕妇作为观察组,其余55例作为对照组。收集两组孕妇的基本资料及超声检查结果。比较两组胎儿脐动脉血流参数[搏动指数(PI)、阻力指数(RI)、收缩末期最大血流速度/舒张末期最大血流速度(S/D)],检测两组孕妇分娩前的sFlt-1和叶酸水平,以及新生儿脐动脉血乳酸含量和氧化产物[8-羟基脱氧鸟苷(8-OHDG)、丙二醛(MDA)]。通过Pearson法分析sFlt-1、叶酸与胎儿脐动脉血流参数、新生儿脐动脉血乳酸含量及氧化产物的相关性,利用受试者工作特征(ROC)曲线评价孕妇sFlt-1、叶酸对发生胎儿功能窘迫的预测价值。结果观察组PI、RI、S/D均高于对照组(P<0.05)。观察组分娩前血清sFlt-1水平高于对照组(P<0.05),叶酸水平低于对照组(P<0.05)。观察组脐动脉血乳酸、8-OHDG和MDA水平均高于对照组(P<0.05)。Pearson相关性分析结果显示,胎儿脐动脉血流参数、新生儿动脉血乳酸和氧化产物均与sFlt-1水平均呈正相关(P<0.05),与叶酸水平呈负相关(P<0.05)。ROC曲线结果表明,孕妇sFlt-1、叶酸联合预测胎儿宫内窘迫的曲线下面积为0.932(95%CI:0.883,0.982),敏感性为89.6%(95%CI:0.773,0.965),特异性为92.7%(95%CI:0.824,0.980)。结论分娩前检测孕妇血清sFlt-1及叶酸水平对预测胎儿慢性宫内窘迫的发生有重要价值。

5-氨基酮戊酸光动力治疗对鲍温病皮损中p53 Caveolin-1表达的影响

目的:探讨5-氨基酮戊酸光动力疗法对鲍温病皮损中p53、Caveolin-1表达的影响及意义。方法:运用5-氨基酮戊酸光动力疗法治疗鲍温病及周围正常皮肤组织各40例,采用免疫组织化学技术(SP法)检测光动力治疗前后鲍温病及周围正常皮肤组织中p53、Caveolin-1的阳性细胞表达率。结果:治疗前p53蛋白在正常皮肤组织及BD中表达的阳性率分别为10%、40%(χ^(2)=11.202,P<0.001),差异有统计学意义。治疗后p53在正常皮肤组织及BD的阳性率为10%、5%(χ^(2)=0.712,P=0.399),两者间差异无统计学意义。治疗前后p53在BD中的阳性表达率差异有统计学意义(χ^(2)=14.811,P<0.001)。治疗前Caveolin-1在正常皮肤组织及BD中阳性表达率为15%、55%(χ^(2)=14.449,P<0.001),两者间差异有统计学意义。治疗后正常皮肤组织及BD中Caveolin-1的阳性率为5%、12.5%(χ^(2)=0.816,P=0.366),差异无统计学意义。治疗前后Caveolin-1在BD中的阳性表达率差异有统计学意义(χ^(2)=19.013,P<0.001)。BD中p53与Caveolin-1阳性表达呈正相关性(r=0.533,P=0.015)。结论:p53及Caveolin-1的高表达可能与BD的发生密切关联,且ALA-PDT能够抑制p53及Caveolin-1的表达,从而抑制疾病的发展。通过更大样本量的研究,p53及Caveolin-1可能会成为皮肤相关疾病的诊断工具,并为其治疗提供新的靶点。

丹酚酸B通过SIRT1/PGC-1α通路对Aβ_(1-42)干预N2A细胞保护作用研究

目的观察沉默信息调节因子2相关酶1(SIRT1)/过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)的表达及检测活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量和线粒体膜电势,探讨丹酚酸B(SalB)减轻β淀粉样多肽1-42(Aβ1-42)干预小鼠来源神经瘤母细胞(N2A)后氧化应激损伤的作用及机制。方法使用10μM Aβ1-42寡聚体干预N2A细胞构建阿尔茨海默病(AD)细胞模型,使用40μM SalB干预细胞为对照组,模型组和SalB干预组。使用MTT法检测不同实验组细胞活力;DCFH-DA染色测定实验组细胞内ROS水平;ELISA法检测SOD,MDA水平;Western blot法和RTPCR法分别检测不同实验组SIRT1、PGC-1α蛋白和mRNA水平。结果与Aβ干预N2A细胞构建的模型组相比,SalB组处理后的模型组细胞活力显著升高(P<0.001),SalB组细胞中ROS水平显著下降(P<0.01),SOD水平显著上升(P<0.001),MDA生成显著减少(P<0.05),有效恢复线粒体膜电势(P<0.05)。另外,SalB处理后模型组细胞的SIRT1、PGC-1α蛋白和mRNA水平均升高。结论SalB可以显著降低Aβ干预N2A细胞后诱导的氧化应激反应,减少ROS产生及下调MDA水平,上调SOD水平,该神经保护作用可能与上调SIRT1/PGC-1α通路相关。

痛风性关节炎患者血清RETN、Beclin-1的表达及其临床意义

目的探讨痛风性关节炎(GA)患者血清抵抗素(RETN)、Beclin-1的表达特点,分析其与GA临床特征及临床疗效的关系。方法将2019年1月至2022年12月东莞市人民医院收治的82例GA患者(GA组)和60例健康志愿者(对照组)纳入研究。GA患者治疗前后(对照组体检当日)检测血清RETN、Beclin-1的表达,比较不同临床特征和疗效GA患者血清RETN、Beclin-1表达差异。Pearson相关性分析GA患者血清RETN、Beclin-1表达与尿酸(UA)水平的相关性。采用受试者工作特征(ROC)曲线分析血清RETN、Beclin-1对GA的诊断价值。结果GA组血清RETN水平高于对照组,Beclin-1相对表达水平低于对照组(P<0.05)。急性期、病程≥5年、受累关节≥5个、年发作频率≥3次GA患者血清RETN水平高于慢性期和间歇期、病程<5年、受累关节<5个、年发作频率<3次GA患者(P<0.05),Beclin-1相对表达水平低于慢性期和间歇期、病程<5年、受累关节<5个、年发作频率<3次GA患者(P<0.05)。GA患者血清UA水平与RETN水平呈正相关(r=0.674,P<0.05),与Beclin-1相对表达水平呈负相关(r=-0.568,P<0.05)。有效组治疗后血清RETN水平低于无效组,Beclin-1相对表达水平高于无效组(P<0.05)。联合RETN、Beclin-1诊断GA的曲线下面积为0.921,高于单独诊断(Z=3.752、3.154,P<0.05)。结论GA患者血清RETN水平增高,Beclin-1相对表达水平降低,且与UA水平增高、GA急性期、病程延长、受累关节数量和年发作频率增加及治疗无效有关。RETN、Beclin-1可作为GA诊断的标志物。

泛癌分析揭示SREK1在低级别胶质瘤中促进CD274表达

目的剪接调节谷氨酸和富赖氨酸的蛋白质1(SREK1)在多种肿瘤中的泛癌分析,揭示SREK1在泛癌中的作用。方法利用在线数据库GEPIA 2、TIMER 2.0、TISIDB和cBioPortal分析SREK1表达对肿瘤患者预后的影响、在低级别胶质瘤(LGG)肿瘤组织中的表达、遗传变异的特征及其表达对肿瘤组织中免疫细胞的浸润和免疫—肿瘤靶基因的相关性分析。结果LGG肿瘤组织中,SREK1表达与记忆B细胞、活化的CD4+T细胞、Th2细胞、中性粒细胞、NKT细胞以及单核细胞和CD56dimNK细胞的浸润存在相关性(P均<0.05)。SREK1与免疫—肿瘤靶基因如信号传导及转录激活蛋白3(STAT3)、Ⅰ型干扰素受体1(IFNAR1)、核受体亚家族3C组成员1(NR3C1)和表皮生长因子受体(EGFR)、表面抗原分化簇274(CD274)等表达在LGG中均呈正相关(P均<0.05)。结论SREK1是LGG患者的危险因子之一,可能通过促进CD274的表达来加剧LGG的进展。