The anti-HIV-1 activity of polyphenols from Phyllanthus urinaria and the pharmacokinetics and tissue distribution of its marker compound, gallic acid

Objective:To investigate the in vitro anti-HIV-1 activities and its associated mechanism of action of an extract isolated from Phyllanthus urinaria (P.urinaria) and to develop an HPLC test method for detecting gallic acid (GA) in plasma and tissues to study its pharmacokinetics and tissue distribution in rats.Methods:An extract of P.urinaria was isolated and purified by phytochemistry and chromatography techniques.The anti-HIV-1 activities and toxicities of the extract and its component GA were determined in human T lymph cells (MT-4) by theMTTr method.The mechanism of its anti-HIV-1 action was studied to examine the in vitro binding of its components with HIV-1 target proteins by Biacore technique.The pharmacokinetics and tissue distribution of GA were investigated after oral administration of polyphenol extract (PE) and pure GA in rats.The concentrations of GA in plasma and tissues were determined by HPLC.Results:The PE and GA isolated from P.urinaria had anti-HIV-1 activities with IC50s of 0.61 μg/mL and 0.76 μg/mL,respectively.The Biacore study indicated that PE and GA interacted with HIV-1 RT,gp120,and P24.The pharmacokinetic parameters Tmax,Cm ax,AUC0-t,and T1/2 for GA were (60.0 ± 3.0) minutes,(2.87 ± 0.50) μg·mL-1,(343.5 ± 11.2) mg·min·L-1,and (113.3 ± 9.3) minutes while the parameters for GA in the PE were (10.0 ± 1.3) minutes,(3.89 ± 0.90) μg·mL-1,(394.7 ± 14.0) mg· min· L-1,and (81.7 ± 4.1) minutes,respectively.GA was detected in rat lungs,liver,kidneys,heart and spleen.Conclusion:APE isolated from P.urinaria containing GA has anti-HIV-1 activities.GA is quickly absorbed and slowly eliminated in rats after oral administration.The pharmacokinetics of GA administered as a PE is desirable,and it is widely distributed in the main tissues of lung and liver.Both its properties and anti-HIV-1 activities make it of interest for further studies.

A dicistrovirus increases pupal mortality in Spodoptera frugiperda by suppressing protease activity and inhibiting larval diet consumption

Understanding interactions between viruses and their hosts is conducive to enabling better application of viruses as biocontrol agents.Certain viruses carried by parasitic wasps enhance the parasitic efficiency of wasp-larvae by protecting them against the immune system of their Lepidopteran host.However,the relationship between prey pests and viruses found in predatory natural enemies remains unclear.Herein,we report the interaction between Arma chinensis virus-1(AcV-1),originally isolated from a predatory natural enemy,Arma chinensis(Hemiptera:Pentatomidae),and one of its prey species,Spodoptera frugiperda(Lepidoptera:Noctuidae).The results showed that the AcV-1 virus appeared harmful to the novel host S.frugiperda by inhibiting larval diet consumption and increasing pupal mortality.Meanwhile,sequencing data indicated that the virus altered the gene expression profiles of S.frugiperda.KEGG analysis showed that the proteasome and phagosome pathways related to protein degradation and immune response were significantly enriched.Although the expression levels of digestive enzyme genes did not change significantly,the total protease activity of AcV-1 virus-positive individuals was significantly decreased,suggesting that the virus inhibited diet consumption of S.frugiperda via the down-regulation of digestive enzyme activities.These results indicate that a virus initially isolated in a predatory natural enemy can decrease the fitness of its prey species.The virus was found to impact the host proteasome and phagosome pathways related to protein degradation and immunity,providing a potential mechanism to enhance controlling efficiency.

Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma

BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.

Diabetic Retinopathy: Diagnostic Challenges and Impact of Physical Activity

Introduction: Diabetes represents a major public health challenge, affecting over 463 million people according to the World Health Organization (WHO). Among its complications, diabetic retinopathy stands out as the leading cause of blindness in industrialized countries. Physical activity is now recognized as a cornerstone of diabetes management, and its impact on diabetic retinopathy is of growing interest. Observation: Mr. A.E, a 54-year-old man, presents with progressive deterioration of his vision. Family history of diabetes and hypertension is noted. He engages in one hour of physical activity daily, including treadmill running and indoor cycling. Despite recent optical correction, his visual acuity remains at 3/10 unimproved. Ocular imaging, notably fluorescein retinal angiography and optical coherence tomography, reveals proliferative diabetic retinopathy with bilateral macular edema. Blood tests, performed after physical activity, show normal values of blood glucose and HbA1c, delaying the initiation of treatment and promoting the progression of retinopathy. Despite appropriate management, no significant improvement in visual function is observed during follow-up. Conclusion: The management of diabetic retinopathy requires an approach integrating physical activity. A better understanding of the interaction between physical activity and diabetic retinopathy is needed to optimize prevention and treatment strategies.

Diabetes and high-glucose could upregulate the expression of receptor for activated C kinase 1 in retina

BACKGROUND Diabetic retinopathy(DR)is a major ocular complication of diabetes mellitus,leading to visual impairment.Retinal pigment epithelium(RPE)injury is a key component of the outer blood retinal barrier,and its damage is an important indicator of DR.Receptor for activated C kinase 1(RACK1)activates protein kinase C-ε(PKC-ε)to promote the generation of reactive oxygen species(ROS)in RPE cells,leading to apoptosis.Therefore,we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS,thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR.AIM To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR.METHODS In this study,Sprague-Dawley rats and adult RPE cell line-19(ARPE-19)cells were used as in vivo and in vitro models,respectively,to explore the role of RACK1 in mediating PKC-εin early DR.Furthermore,the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model.RESULTS Streptozotocin-induced diabetic rats showed increased apoptosis and upregulated expression of RACK1 and PKC-εproteins in RPE cells following a prolonged modeling.Similarly,ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε,accompanied by an increases in ROS production,apoptosis rate,and monolayer permeability.However,silencing RACK1 significantly downregulated the expression of PKC-εand ROS,reduced cell apoptosis and permeability,and protected barrier function.CONCLUSION RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.

Diagnostic Value of the Padua Score Combined with Thrombotic Biomarker Tissue Plasminogen Activator Inhibitor-1 (tPAI-1) Detection for the Risk of Deep Vein Thrombosis in Patients with Pulmonary Heart Disease

This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with pulmonary heart disease.These patients often exhibit symptoms similar to venous thrombosis,such as dyspnea and bilateral lower limb swelling,complicating differential diagnosis.The Padua Prediction Score assesses the risk of venous thromboembolism(VTE)in hospitalized patients,while tPAI-1,a key fibrinolytic system inhibitor,indicates a hypercoagulable state.Clinical data from hospitalized patients with cor pulmonale were retrospectively analyzed.ROC curves compared the diagnostic value of the Padua score,tPAI-1 levels,and their combined model for predicting DVT risk.Results showed that tPAI-1 levels were significantly higher in DVT patients compared to non-DVT patients.The Padua score demonstrated a sensitivity of 82.61%and a specificity of 55.26%at a cutoff value of 3.The combined model had a significantly higher AUC than the Padua score alone,indicating better discriminatory ability in diagnosing DVT risk.The combination of the Padua score and tPAI-1 detection significantly improves the accuracy of diagnosing DVT risk in patients with pulmonary heart disease,reducing missed and incorrect diagnoses.This study provides a comprehensive assessment tool for clinicians,enhancing the diagnosis and treatment of patients with cor pulmonale complicated by DVT.Future research should validate these findings in larger samples and explore additional thrombotic biomarkers to optimize the predictive model.

Synthesis, Characterization and Biological Activity Evaluation of Schiff Bases Derived from 1,8-Diaminonaphtalène

The compounds have been synthesized and characterized by routine MS, IR and NMR spectrometry methods. The compounds are all active on bacterial strains with the exception of Salmonella typhimirium, with a MIC value of 7.5 mg/mL. They show a percentage of anti-radical activity of 75.476 ± 5.070 for the compound DAN-S and of 68.142 ± 6.539 for the compound DAN-OV. The compounds are sensitive to the two champions used. DAN-S compound is then the most active.

Synthesis, Structural Characterization and Antimicrobial Activity of a Novel Cobalt(II) Complex Based on 3-Methyl-1-Phenyl-4-(2-Thienoyl)-Pyrazol-5-One

New cobalt(II) complex, [Co(O2C15H11N2S)2(OH2)2]∙2H2O (1∙2H2O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)2∙6H2O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H2O. Compound 1∙2H2O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H2O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H2O displayed moderate activity (10 ∙2H2O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).

Synthesis, Structural Characterization and Antimicrobial Activity of a Novel Cobalt(II) Complex Based on 3-Methyl-1-Phenyl-4-(2-Thienoyl)-Pyrazol-5-One

New cobalt(II) complex, [Co(O2C15H11N2S)2(OH2)2]∙2H2O (1∙2H2O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)2∙6H2O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H2O. Compound 1∙2H2O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H2O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H2O displayed moderate activity (10 ∙2H2O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).

Synthesis and anti-HIV-1 activity of the conjugates of gossypol with oligopeptides and D-glucosamine

A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV- 1I activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, D-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1ⅢB into target cell. which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and D-glucosamine were important moities to prepare gossypol derivatives as HIV- 1 entry inhibitors besides certain amino acids.

GTPase Activity of MxB Contributes to Its Nuclear Location, Interaction with Nucleoporins and Anti-HIV-1 Activity

The human myxovirus resistance 2(Mx2/Mx B)protein,a member of interferon(IFN)-inducible dynamin-like large GTPases,restricts a number of virus infections.Inhibition of these viruses occurs at poorly-defined steps after viral entry and has a common requirement for Mx B oligomerization.However,the GTPase activity is essential for the anti-viral effects of Mx B against herpesviruses and HBV but not HIV-1.To understand the role of Mx B GTPase activity,including GTP binding and GTP hydrolysis,in restriction of HIV-1 infection,we genetically separated these two functions and evaluated their contributions to restriction.We found that both the GTP binding and hydrolysis function of Mx B involved in the restriction of HIV-1 replication.The GTPase activity of Mx B contributed to its nuclear location,interaction with nucleoporins(NUPs)and HIV-1 capsids.Furthermore,Mx B disrupted the association between NUPs and HIV-1 cores dependently upon its GTPase activity.The function of GTPase activity was therefore multi-faceted,led to fundamentally distinct mechanisms employed by wild-type Mx B and GTPase activity defective Mx B mutations to restrict HIV-1 replication.

白藜芦醇通过调节SIRT1/AMPK信号通路介导自噬反应对膝关节骨性关节炎大鼠细胞凋亡的影响

目的:从沉默信息调节因子1(SIRT1)/腺苷酸活化蛋白激酶(AMPK)信号通路介导自噬角度,探讨白藜芦醇对大鼠膝关节骨性关节炎(KOA)软骨细胞凋亡的影响。方法:50只健康Wistar大鼠随机分为对照组、模型组、白藜芦醇组、白藜芦醇+SIRT1抑制剂组、自噬激活剂组,每组10只。除对照组外其余大鼠均通过注射弗氏完全佐剂造模法复制KOA大鼠模型,白藜芦醇组、白藜芦醇+AMPK抑制剂组、自噬激活剂组分别使用10μmol/kg白藜芦醇、10μmol/kg白藜芦醇+10 mg/kg EX527、2 mg/kg雷帕霉素进行干预,4周后,观察大鼠Lequesne MG膝关节级别;测定大鼠膝关节液中IL-6、肿瘤坏死因子β(TNF-β)水平;HE染色与TUNEL染色观测大鼠膝关节软骨组织形态及凋亡情况;透射电子显微镜观察大鼠软骨细胞自噬情况;Western blot法检测SIRT1、p-AMPK、AMPK、LC3、Beclin-1蛋白表达。结果:与对照组相比,模型组局部反应、步态反应、关节活动、关节肿胀程度加重(P<0.05);与模型组相比,白藜芦醇组、自噬激活剂组局部反应、步态反应、关节活动、关节肿胀程度减轻(P<0.05)。与对照组相比,模型组大鼠软骨组织细胞排列紊乱,粗糙,存在纤维化变性、边缘丘状隆起,细胞器减少,可见空泡变性,自噬小体数目增多,膝关节液IL-6、TNF-β水平、软骨细胞凋亡率、Beclin-1和LC3B/A升高(P<0.05),软骨组织SIRT1、p-AMPK/AMPK降低(P<0.05);与模型组相比,白藜芦醇组、自噬激活剂组大鼠软骨组织细胞排列紊乱、边缘丘状隆起等现象有改善,自噬小体数目增多,膝关节液IL-6、TNF-β水平、软骨细胞凋亡率降低(P<0.05),软骨组织SIRT1、p-AMPK/AMPK、Beclin-1和LC3B/A水平升高(P<0.05);SIRT1抑制剂可逆转白藜芦醇组对大鼠软骨细胞的保护作用。结论:白藜芦醇可能是通过激活SIRT1/AMPK通路介导自噬KOA大鼠软骨细胞凋亡,SIRT1抑制剂可逆转此过程。

TRPC1与BK-α的表达对大鼠糖尿病肾病的影响

目的 探究瞬时受体电位C1(transient receptor potential channel 1,TRPC1)蛋白和大电导钙离子激活钾通道α亚单位(large conductance Ca^(2+)-activated K^(+)channel α subunit,BK-α)蛋白对大鼠糖尿病肾病(diabetic kidney disease,DKD)的影响。方法 将SD大鼠随机分为对照组(n=15)和模型组(n=15)。利用高脂饲料和链脲佐菌素(streptozocin,STZ)构建DKD模型。采用血糖分析仪检测大鼠血糖变化;采用全自动生化分析仪检测大鼠肾功能水平;HE染色检测肾组织的病理变化以确定造模成功。实时荧光定量PCR(RT-qPCR)和蛋白免疫印迹分别检测肾组织TRPC1和BK-α的mRNA和蛋白表达水平;免疫组化检测TRPC1和BK-α的分布和表达情况。结果 模型组大鼠空腹血糖(fasting plasma glucose,FPG)、尿白蛋白排泄率(urinary albumin excretion rates,UAER)、血尿素氮(blood urea nitrogen,BUN)和肌酐(creatinine,Cr)均显著高于对照组(P <0.01);模型组大鼠肾小管内壁细胞出现膨胀现象,部分细胞脱离;可见肾小管发生病变或死亡;此外,在许多肾小管及肾间质区域发现有中性白细胞及其残骸;以上HE染色结果提示,DKD模型复制成功。TRPC1和BK-α在肾小球部位最为丰富,且模型组大鼠肾组织中TRPC1和BK-α的mRNA和蛋白水平都显著高于对照组(P <0.05)。结论 大鼠糖尿病肾病影响TRPC1和BK-α在肾组织中的分布和表达。

Expression, Purification and Insecticidal Activity Analysis of Cry1Ac without Helix α-1

[Objective] This study aimed to analyze the expression, purification and insecticidal activity of Cry1Ac without helix α-1 of domain I in E. coli. [Method] Plasmid of B. thuringiensis HD-1 was used as the template for amplification of Cry1Ac gene, which was linked with pET28a vector to construct the recombinant plasmid. After transformation and IPTG induction, expression of target protein was detected by using SDS-PAGE method. Target protein was extracted and coated on the surface of feed for H. armigera to determine the insecticidal activity. [Result] Cry1Acdela1 gene could normally express the target protein in E. coli. However, the target protein existed in the form of inclusion body. Results of bioassay analysis showed that under the same concentration, fatality rate of activated Cry1Ac toxin reached above 75%, while that of Cry1Acdelα1 was only about 10%. [Conclusion] E. coli-expressed Cry1Acdelα1 had no insecticidal activity against H. armigera.

1-MCP协同活性炭处理抑制鲜切胡萝卜木质化形成研究

鲜切胡萝卜在贮藏过程易发生木质化,导致品质下降。为探究1-MCP协同活性炭处理对鲜切胡萝卜木质化抑制保鲜效果,文章分析了乙烯利、活性炭、1-MCP和1-MCP协同活性炭等4种处理方式对鲜切胡萝卜硬度、总酚、抗氧化性、PPO、POD、PAL和木质素含量的影响。结果表明:1-MCP协同活性炭处理显著延缓了胡萝卜硬度下降;在贮藏第10 d总酚含量达0.20 mg GAE·g^(−1),显著高于其他处理组(P<0.05);抗氧化性也保持最高水平;DPPH自由基清除活性为0.90μmol TE·g^(−1);PPO、POD活性分别为0.23 U·g^(−1)和61.08 U·g^(−1),显著低于对照组(P<0.05);PAL活性和木质素含量分别为81.67 U·g^(−1)和65.88 mg·g^(−1),也显著低于对照组(P<0.05)。可见,1-MCP协同活性炭处理可有效抑制鲜切胡萝卜木质化,提升其贮藏品质。

miR-132-3p/CAMTA1对I-125粒子处理的面神经损伤大鼠施万细胞的调控作用

目的探讨miR-132-3p通过钙调素结合转录因子1(CAMTA1)对I-125粒子处理的面神经损伤大鼠(FNI)中施万细胞的调控作用。方法用I-125粒子辐射大鼠施万细胞,并在细胞中转染miR-132-3p mimic、miR-132-3p inhibitor以及sh-CAMTA1。免疫荧光检测S100B和β-TubulinⅢ荧光强度。RT-qPCR检测miR-132-3p的表达,Western blot检测CAMTA1蛋白表达。EdU染色评估细胞增殖,Transwell检测细胞迁移。同时,构建FNI大鼠模型并在大鼠面部植入I-125粒子,HE、LFB染色以及IF染色评估大鼠面神经组织的病理损伤。StarBase v2.0数据库和双荧光素酶报告实验验证miR-132-3p和CAMTA1的靶向关系。结果S100B和β-TubulinⅢ在大鼠施万细胞中显著表达。I-125粒子辐射组中miR-132-3p表达降低(P<0.001),抑制细胞的增殖(P<0.001)和迁移(P<0.001)。过表达miR-132-3p或敲降CAMTA1显著促进施万细胞的增殖(P<0.001)和迁移(P<0.05),敲降miR-132-3p则具有相反的作用。机制研究显示,miR-132-3p靶向负调控CAMTA1。体内实验结果显示,过表达miR-132-3p通过抑制CAMTA1的蛋白表达,减弱I-125粒子对FNI大鼠面神经损伤的促进作用。结论过表达miR-132-3p抑制CAMTA1的表达,促进施万细胞的增殖和迁移,抑制I-125对FNI大鼠面神经损伤的促进作用。

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。

早期胃癌患者血清TK1、STAT1、sB7-H4水平变化及对内镜黏膜下剥离术预后的预测价值

目的 探究早期胃癌患者血清胸苷激酶1(TK1)、信号转导和转录活化因子1(STAT1)、可溶性B7-H4(sB7-H4)水平变化,并分析其对内镜黏膜下剥离术(ESD)预后的预测价值。方法 前瞻性选取2019年1月至2022年7月郑州大学第一附属医院300例接受ESD手术的早期胃癌患者,检测围手术期(术前、术后3 d、术后7 d)血清TK1、STAT1、sB7-H4水平,术后接受为期1 a随访,根据有无复发分为复发组(22例)与未复发组(278例)。比较两组患者的临床资料及血清TK1、STAT1、sB7-H4水平。评价血清TK1、STAT1、B7-H4水平预测早期胃癌患者ESD术后复发的价值。结果 所有患者术后7 d血清TK1、sB7-H4水平<术后3 d<术前(P<0.05),所有患者术后7 d血清STAT1水平>术后3 d>术前(P<0.05)。复发组术后3、7 d的血清TK1、sB7-H4水平均高于未复发组,STAT1水平均低于未复发组(P<0.05)。术后3、7 d血清TK1、sB7-H4、STAT1联合预测复发的曲线下面积(AUC)分别为0.901、0.944,均大于各时间点三项血清指标单独预测,且术后7 d预测价值更高,此时最佳敏感度、特异度分别为90.91%、86.33%。结论 血清TK1、sB7-H4、STAT1水平变化与早期胃癌患者ESD术后复发密切相关,且在临床早期预测患者术后复发方面具有较高预测效能。

血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6在结核性胸膜炎胸膜纤维化患者中的变化及临床意义

目的探讨血清和胸腔积液纤溶酶原激活剂抑制物-1(PAI-1)、转化生长因子-β(TGF-β)、血管内皮生长因子(VEGF)、白细胞介素-6(IL-6)在结核性胸膜炎胸膜纤维化患者中的变化及临床意义。方法选取2020年7月至2023年7月该院收治的103例结核性胸膜炎胸膜纤维化患者作为研究对象,治疗2周后,根据糖皮质激素治疗疗效将其分为显效组、非显效组。比较两组治疗前及治疗1、2周后血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平。采用Spearman相关分析血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平与疗效的相关性。治疗2周后血清PAI-1、TGF-β、VEGF、IL-6水平与胸腔积液中该指标水平之间进行Pearson相关分析。绘制受试者工作特征曲线分析治疗1、2周后血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平对结核性胸膜炎胸膜纤维化患者疗效的预测价值。结果两组治疗1、2周后血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平低于治疗前,显效组治疗1、2周后血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平低于非显效组,差异有统计学意义(P<0.05)。治疗1、2周后血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平与疗效呈负相关(P<0.05)。治疗2周后血清PAI-1、TGF-β、VEGF、IL-6水平和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平呈正相关(r=0.761、0.783、0.812、0.741,均P<0.05)。治疗1、2周后血清和胸腔积液各指标联合检测的曲线下面积(AUC)大于其单独指标的AUC(P<0.05)。结论结核性胸膜炎胸膜纤维化患者血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平与疗效有关,血清及胸腔积液PAI-1、TGF-β、VEGF、IL-6联合检测的预测价值较好,能够为临床干预提供参考依据。

冬凌草甲素调节JAK2/STAT3/SOCS-1信号通路对糖耐量异常大鼠胰岛素抵抗的影响

目的探讨冬凌草甲素(Oridonin,Ori)对糖耐量异常(impaired glucose tolerance,IGT)大鼠胰岛素抵抗(insulin resistance,IR)的影响及作用机制。方法采用高脂饮食喂养联合链脲佐菌素注射法构建IGT大鼠IR模型,大鼠分为正常组(CT组)、IGT模型组(IGT组)、Ori组(10 mg·kg^(-1)·d^(-1))、Ori+Colivelin(COL)组(10 mg·kg^(-1)·d^(-1)Ori+2 mg/kg COL),每组6只。血糖检测仪测定空腹血糖(FPG)、葡萄糖耐量试验(OGTT)2 h血糖(2 hPG),ELISA试剂盒测定空腹胰岛素(FINS)、单核细胞趋化蛋白1(MCP-1)、肿瘤坏死因子α(TNF-α)含量,计算胰岛素抵抗指数(HOMA-IR),血液自动分析仪测定血清胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平,HE染色观察肝脏病理形态,Western blot验证附睾脂肪磷酸化(p)-激活Janus激活激酶2(JAK2)、JAK2、p-信号转导和转录激活因子3(STAT3)、STAT3、p-细胞因子信号传导抑制蛋白1(SOCS-1)、SOCS-1蛋白表达。结果与CT组比较,IGT组大鼠肝脏细胞肿胀,胞浆内可见大量大小不一的脂肪空泡,细胞核被脂肪空泡挤压偏位,且发生炎性细胞浸润,FPG、2hPG、FINS、HOMA-IR、TC、TG、LDL-C、MCP-1、TNF-α以及p-JAK2/JAK2、p-STAT3/STAT3、p-SOCS-1/SOCS-1蛋白表达水平升高,血清HDL-C水平下降(P<0.05);与IGT组相比,Ori组大鼠肝脏细胞胞浆内脂肪滴及空泡数量明显减少,细胞肿胀有所缓解,未见炎性细胞浸润,FPG、2hPG、FINS、HOMA-IR、TC、TG、LDL-C、MCP-1、TNF-α以及p-JAK2/JAK2、p-STAT3/STAT3、p-SOCS-1/SOCS-1蛋白表达水平下降,血清HDL-C水平升高(P<0.05);与Ori组相比,Ori+COL组大鼠肝脏脂肪变状况加剧,细胞肿大,血清FPG、2hPG、FINS、HOMA-IR、TC、TG、LDL-C、MCP-1、TNF-α以及p-JAK2/JAK2、p-STAT3/STAT3、p-SOCS-1/SOCS-1蛋白表达水平升高,血清HDL-C水平下降(P<0.05)。结论Ori对IGT大鼠IR的缓解作用可能与抑制JAK2/STAT3/SOCS-1信号通路激活有关。