Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis

BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

Molecular Tissue Engineering: Applications for Modulation of Mesenchymal Stem Cells Proliferation by Transforming Growth Factor β_1 Gene Transfer

The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basis for accelerating articular cartilage repairing using molecular tissue engineering technology. TGF β 1 gene at different doses was transduced into the rat bone marrow derived MSCs to examine the effects of TGF β 1 gene transfection on MSCs DNA synthesis, cell cycle kinetics and the expression of proliferating cell nuclear antigen (PCNA). The results showed that 3 μl lipofectamine mediated 1 μg TGF β 1 gene transfection could effectively promote the proliferation of MSCs best; Under this condition (DNA/Lipofectamine=1μg/3μl), flow cytometry and immunohistochemical analyses revealed a significant increase in the 3 H incorporation, DNA content in S phase and the expression of PCNA. Transfection of gene encoding TGF β 1 could induce the cells at G0/G1 phase to S1 phase, modulate the replication of DNA through the enhancement of the PCNA expression, increase the content of DNA at S1 phase and promote the proliferation of MSCs. This new molecular tissue engineering approach could be of potential benefit to enhance the repair of damaged articular cartilage, especially those caused by degenerative joint diseases.

Plasma Levels of Transforming Growth Factor-Beta 1 in Women with Pelvic Organ Prolapse

Objective: In women with pelvic organ prolapse (POP), decreased expression of transforming growth factor-beta 1 (TGF-β1) has been shown in POP tissues. However, no studies have evaluated plasma TGF-β1 levels in patients with POP, so it is unknown whether they are also changed or not. Therefore, we compared plasma TGF-β1 levels in women with and without POP. Methods: Participants were 49 women with POP and 23 healthy control women. All participants were postmenopausal. We measured plasma TGF-β1 and compared data between patients with POP and controls, and between patients with uterine prolapse (UP, n = 19) and those with a cystocele (CC, n = 30). In addition, in patients, we assessed the POP quantification system (POP-Q) stage. Results: Plasma TGF-β1 levels were significantly lower in patients than in healthy controls. POP-Q stage was not significantly different between the UP and CC subgroups, but POP-Q stage IV was diagnosed in 63% of patients with UP and 7% of those with CC. Plasma TGF-β1 levels were significantly lower in the CC subgroup than in the UP subgroup. Conclusion: Plasma TGF-β1 is decreased in POP. It remains unclear whether the lower levels indicate a reduction in systemic TGF-β1 activity, but they can be assumed to reflect reduced TGF-β1 expression in POP tissues.

Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

Hypoxia-inducible factor 1alpha and vascular endothelial growth factor in Glioblastoma Multiforme:a systematic review going beyond pathologic implications

Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

Osteogenic Potential of Cultured Bone Marrow Stromal Cells Transfected with Transforming Growth Factor β_1 Gene in vitro

To study the osteogenic potential of cultured bone marrow stromal cells transfected with transforming growth factor β 1 gene in vitro , cultured BMSCs were transfected with the complexes of pcDNA 3 TGF β 1 and Lipofectamine Reagent in vitro . The cell proliferation was detected by MTT method and the morphological features of transfected BMSCs was observed. ALP stains and PNP method were used to measure ALP activity. In addition, the collagen type Ⅰ propeptides and mineralized matrixes were examined by immunohistochemical staining and tetracycline fluorescence labeling respectively. The morphological and biological characters of the transfected BMSCs were similar to those of osteoblasts and the cell proliferation was promoted. The cell layer displayed strong positive reaction for ALP stains and immunohistochemical staining. ALP activity and collagen type Ⅰ expression increased remarkably after transfection. Mineralized matrixes formed earlier and more in transfected BMSCs as compared with control group. It is concluded that transfecting with TGF β 1 gene could promote the osteogenic potential of cultured BMSCs.

Concomitant epidermal growth factor receptor mutation/c-ros oncogene 1 rearrangement in non-small cell lung cancer: A case report

BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.

儿童慢性粒细胞白血病慢性期红细胞参数及血清bFGF、TGF-β1、VEGF表达变化分析

目的探究儿童慢性粒细胞白血病(CML)慢性期红细胞参数及血清碱性成纤维细胞生长因子(bFGF)、转化生长因子β1(TGF-β1)及血管内皮生长因子(VEGF)表达变化。方法前瞻性选取2020年1月至2023年1月在首都医科大学附属北京儿童医院进行治疗的54例CML慢性期患儿为研究组,另随机抽取46名同期在本院进行体检的健康儿童为健康对照组。研究组给予酪氨酸激酶抑制剂治疗。比较两组间红细胞参数及血清bFGF、TGF-β1、VEGF表达变化,并比较研究组治疗前后红细胞参数及血清bFGF、TGF-β1、VEGF表达水平。结果研究组的RBC、血红蛋白、红细胞压积(HCT)及平均红细胞血红蛋白浓度(MCHC)水平分别为(3.45±0.04)×10^(12)/L、(102.33±1.15)g/L、(32.03±0.61)%、322.15±2.58,均显著低于对照组[(4.98±0.03)×10^(12)/L、(149.78±1.88)g/L、(44.33±0.31)%、334.12±0.77],平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)及红细胞体积分布宽度(RDW)水平分别为(91.44±0.77)fL、(33.15±2.55)pg、(17.55±0.12)%,均显著高于对照组[(89.88±0.34)fL、(30.24±0.16)pg、(12.66±0.11)%],差异均有统计学意义(P<0.05)。研究组的血清bFGF、VEGF水平分别为(30.66±9.66)、(128.68±30.58)pg/mL,均显著高于对照组[(5.26±1.54)、(70.66±11.26)pg/mL],TGF-β1水平为(38.22±8.06)μg/L,显著低于对照组[(78.66±8.13)μg/L],差异均有统计学意义(P<0.05)。治疗后,研究组患儿的RBC、血红蛋白、HCT、MCV及MCH水平均较治疗前显著降低,MCHC及RDW水平均较治疗前显著升高,差异均有统计学意义(P<0.05)。研究组治疗后的血清bFGF、VEGF水平均较治疗前显著降低,TGF-β1水平较治疗前显著升高,差异均有统计学意义(P<0.05)。结论在儿童CML慢性期患儿中可见血细胞参数明显异常,血清bFGF、VEGF水平显著升高,TGF-β1水平显著降低。酪氨酸激酶抑制剂治疗CML慢性期能有效改善患儿红细胞形态及功能,抑制肿瘤细胞生长,临床疗效显著,值得临床推广使用。

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。

褐藻聚合酚下调TGF-β_(1)/Smads信号通路抑制大肠癌细胞增殖与侵袭

目的探讨褐藻聚合酚(PFFE-A)对大肠癌细胞增殖与侵袭的影响,以及其对转化生长因子β_(1)(TGF-β_(1))及母体抗生物皮肤生长因子同源物2/3(Smad2/3)通路的调控作用。方法细胞分组:依次以50、100、150μmol·L-1的小、中、大剂量的PFFE-A干预细胞,另设立正常对照组细胞。5-乙炔基-2'脱氧尿苷(EdU)染色检测细胞的增殖;Transwell小室检测细胞的侵袭能力;异种种植结肠癌裸鼠模型检测细胞的体内生长与转移能力;实时荧光定量聚合酶链反应(RT-qPCR)检测细胞中上皮间质转化(EMT)相关基因的表达;Western blotting检测细胞中TGF-β_(1)、p-Smad2/3的表达水平。结果与正常对照组比较,PFFE-A小、中、大剂量组细胞的增殖率、侵袭细胞数、肿瘤瘤体质量、病灶转移比例、神经型钙黏附蛋白(N-cadherin)的mRNA的表达、TGF-β_(1)和p-Smad2/3的表达明显下降(P<0.05),E-钙黏蛋白(E-cadherin)的mRNA的表达明显升高(P<0.05),具有明显的剂量依赖性(P<0.05)。结论PFFE-A能抑制肿瘤细胞的EMT过程,抑制大肠癌细胞HT29的体外增殖与侵袭能力,下调其体内生长与转移的能力,这可能是通过下调TGF-β_(1)/Smads信号实现的。

血清LRG1、TGF-β1水平与急性脑梗死颈动脉内膜中层厚度及近期预后不良的关系

目的探讨血清富亮氨酸α-2糖蛋白-1(LRG1)、转化生长因子-β1(TGF-β1)水平与急性脑梗死(ACI)颈动脉内膜中层厚度(IMT)及近期预后不良的关系。方法选取2020年1月至2023年1月在苏州市广济医院诊治的123例ACI患者,根据IMT将患者分为正常组(23例)、增厚组(30例)和斑块组(70例),另选取同期苏州市广济医院35例体检健康者作为健康对照组,比较4组血清LRG1、TGF-β1水平及IMT。随访3个月,根据预后情况将患者分为预后良好组(75例)和预后不良组(48例),采用Pearson法分析血清LRG1、TGF-β1与IMT的相关性;采用单因素和多因素Logistic回归分析ACI患者近期预后不良的危险因素;采用受试者工作特征(ROC)曲线分析血清LRG1、TGF-β1水平对ACI患者近期预后不良的预测价值。结果健康对照组、正常组、增厚组、斑块组血清LRG1水平依次升高,TGF-β1水平则依次降低(P<0.05)。Pearson相关性分析显示,血清LRG1与IMT呈正相关,TGF-β1则与IMT呈负相关(P<0.05)。预后不良组年龄、合并糖尿病患者占比、入院美国国立卫生研究院卒中量表(NIHSS)评分、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)、白细胞计数(WBC)、C-反应蛋白(CRP)及血清LRG1水平均高于预后良好组(P<0.05),发病至溶栓时间长于预后良好组(P<0.05),血清TGF-β1水平则低于预后良好组(P<0.05)。多因素Logistic回归分析显示,NIHSS评分高、发病至溶栓时间长、血清LRG1水平升高及TGF-β1水平降低均是影响ACI患者近期近期预后不良的危险因素(P<0.05)。ROC曲线结果显示,血清LRG1、TGF-β1单独及联合预测ACI患者近期预后不良的曲线下面积分别为0.824、0.708、0.902。结论ACI患者存在血清LRG1水平升高、TGF-β1水平降低的情况,血清LRG1、TGF-β1水平与IMT及ACI患者近期预后密切相关,联合检测血清LRG1、TGF-β1水平对预测ACI患者近期预后不良有较高的参考价值。

疏血通注射液辅助治疗对老年缺血性脑卒中患者认知功能及TGF-β_(1)、Smad1的影响

目的:探讨疏血通注射液辅助治疗对老年缺血性脑卒中患者认知功能及转化生长因子-β_(1)(TGF-β_(1))、Smad同源物1(Smad1)的影响。方法:选择2021年4月—2023年4月昆山市锦溪人民医院收治的82例老年缺血性脑卒中患者作为研究对象。将随机分为观察组、对照组,各41例。对照组采用常规治疗,观察组在对照组基础上采用疏血通注射液辅助治疗。比较两组认知功能、TGF-β_(1)、Smad1、自理能力和神经功能、不良反应发生率。结果:治疗后,两组简易精神状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)评分高于治疗前,临床痴呆评定量表(CDR)评分低于治疗前,且观察组MMSE、MoCA评分高于对照组,CDR评分低于对照组,差异有统计学意义(P<0.05)。治疗后,两组TGF-β_(1)低于治疗前,Smad1高于治疗前,且观察组TGF-β_(1)低于对照组,Smad1高于对照组,差异有统计学意义(P<0.05)。治疗后,两组日常生活能力量表(ADL)评分高于治疗前,美国国立卫生研究院卒中量表(NIHSS)评分低于治疗前,且观察组ADL评分高于对照组,NHISS评分低于对照组,差异有统计学意义(P<0.05)。观察组不良反应总发生率为7.32%,低于对照组的14.63%,但两组间比较,差异无统计学意义(P>0.05)。结论:疏血通注射液辅助治疗能够有效改善老年缺血性脑卒中患者的认知功能、TGF-β_(1)、Smad1,提高患者自理能力及神经功能,具有较高的安全性。

胰岛素样生长因子1对人RPE细胞分泌TGF-β2、MMP-2的影响及机制研究

目的研究胰岛素样生长因子1(IGF-1)对人视网膜色素上皮细胞(ARPE-19)表达转化生长因子β2(TGF-β2)、基质金属蛋白酶2(MMP-2)的影响,并探索其作用机制。方法ARPE-19细胞分别按不同浓度IGF-1和不同浓度LY294002培养6 h、12 h、24 h、48 h,采用CCK-8法检测细胞活力,确定IGF-1、LY294002的最佳作用浓度与时间。细胞划痕法检测细胞迁移活性。ELISA法检测细胞培养上清液中TGF-β2浓度。将ARPE-19细胞分为对照组、IGF-1组(80μg·L^(-1) IGF-1)、IGF-1+LY294002组(80μg·L^(-1) IGF-1+30 mmol·L^(-1) LY294002)、LY294002组(30 mmol·L^(-1) LY294002),使用无血清DMEM/F12培养基培养,对照组不做任何处理,分别采用RT-PCR、Western blot检测细胞中TGF-β2、MMP-2、磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B(AKT)的mRNA和蛋白表达量。结果与0μg·L^(-1) IGF-1比较,80μg·L^(-1) IGF-1的细胞活力24 h变化显著(P<0.05),故确定其为IGF-1最佳作用浓度和时间。与0 mmol·L^(-1) LY294002比较,24 h的30 mmol·L^(-1) LY294002接近半数抑制浓度,故确定其为LY294002最佳作用时间和浓度。细胞划痕法检测结果显示,0μg·L^(-1) IGF-1组、40μg·L^(-1) IGF-1组、80μg·L^(-1) IGF-1组细胞迁移率整体比较及两两比较差异均有统计学意义(均为P<0.05)。ELISA检测结果显示,0μg·L^(-1) IGF-1组、40μg·L^(-1) IGF-1组、80μg·L^(-1) IGF-1组细胞上清液中TGF-β2浓度整体比较及两两比较差异均有统计学意义(均为P<0.05)。RT-PCR、Western blot检测结果显示,IGF-1、LY294002培养24 h,与对照组比较,IGF-1组细胞中TGF-β2、MMP-2、PI3K、AKT的mRNA与蛋白表达水平均升高,而LY294002组细胞中TGF-β2、MMP-2、PI3K、AKT的mRNA与蛋白表达水平均下降(均为P<0.05);与IGF-1组比较,IGF-1+LY294002组细胞中TGF-β2、MMP-2、PI3K、AKT的mRNA与蛋白表达水平均下降(均为P<0.05)。结论IGF-1能促进ARPE-19细胞增殖、迁移;IGF-1可能通过PI3K/AKT信号通路上调ARPE-19细胞中TGF-β2、MMP-2的表达,参与近视的发生与发展。

不同方法联合放疗治疗薄型瘢痕疙瘩的疗效及对MMPs、HIF-1α、TGF-β1的影响

目的探讨不同方法联合放疗治疗薄型瘢痕疙瘩的疗效及对基质金属蛋白酶(MMPs)、缺氧诱导因子-1α(HIF-1α)及转化生长因子-β1(TGF-β1)的影响。方法回顾性选取2020年10月至2022年9月内蒙古医科大学附属肿瘤医院(内蒙古自治区肿瘤医院)整形外科收治的胸腹部瘢痕疙瘩患者62例(瘢痕疙瘩数94个),依据治疗方法不同分为激光联合放疗(LCR)组(30例,瘢痕疙瘩数47个)、手术联合放疗(SCR)组(32例,瘢痕疙瘩数47个)。LCR组行CO 2点阵LCR,SCR组行SCR。观察两组治疗12个月后临床疗效、复发情况。比较两组治疗前、治疗12个月后的患者与观察者瘢痕评估量表(POSAS)评分、温哥华瘢痕量表(VSS)评分、瘢痕组织基质金属蛋白酶(MMP)-2、MMP-9、HIF-1α、TGF-β1等细胞因子水平的变化。结果LCR组总有效率(93.62%)大于SCR组(76.60%),复发率(4.26%)小于SCR组(19.15%),差异均有统计学意义(P<0.05)。治疗12个月后,LCR组POSAS、VSS评分分别为(23.96±2.64)、(5.28±0.54)分,均低于SCR组[(33.96±3.59)、(6.55±0.68)分],差异均有统计学意义(P<0.05)。LCR组瘢痕组织MMP-2、MMP-9及HIF-1α、TGF-β1表达量分别为111.65±13.55、106.76±12.68、1.24±0.14、1.10±0.12,均低于SCR组(127.96±14.71、121.08±14.33、1.55±0.17、1.22±0.13),差异均有统计学意义(P<0.05)。两组不良反应发生率比较(38.30%vs.46.81%),差异无统计学意义(P>0.05)。结论LCR和SCR均可改善薄型瘢痕疙瘩症状,抑制瘢痕疙瘩复发,但LCR的治愈率更高,复发率更低,对瘢痕组织MMPs及HIF-1α、TGF-β1表达抑制作用更强,且安全性较高,值得临床推荐。

TSP-1和TGF-β在预测肝部分切除术后肝衰竭的临床价值

目的:探讨肝部分切除术后血浆凝血酶敏感蛋白1(TSP-1)与转化生长因子β (TGF-β)动态变化以及其在预测肝部分切除术后肝衰竭(PHLF)的临床价值。方法:回顾性分析2016年1月至2019年3月新疆医科大学第一附属医院收治的113例肝切除术患者临床资料。其中男59例,女54例;平均年龄(41.00±13.98)岁。依据国际肝脏外科研究小组(ISGLS)标准将患者分为PHLF发生组(40例)和PHLF未发生组(73例)。观察两组围手术期血浆TSP-1和TGF-β动态变化,并采用受试者工作特征(ROC)曲线分析TSP-1、TGF-β水平对PHLF的预测价值。根据ROC曲线临界值将TSP-1分为TSP-1high组和TSP-1low组,分析二者与PHLF相关性。两组TSP-1、TGF-β比较采用t检验或MannWhitney秩和检验,率的比较采用χ^(2)检验或Fisher确切概率法。结果:共40例患者出现不同程度的PHLF。PHLF发生组术后第1天及术后第7天TSP-1水平明显高于PHLF未发生组。术后第1天TSP-1、术后第7天TSP-1诊断PHLF的ROC曲线下面积分别为0.725和0.81,灵敏度分别为0.864和0.818,特异度分别为0.647和0.765。结论:PHFL发生与肝切除范围、Child-Pugh分级及术后第1天TSP-1有关。术后第1天TSP-1水平可作为预测PHLF有效的参考指标。

老年患者NLR、TGF-β1、Cav-1水平与颅内大动脉急性闭塞机械取栓术后出血风险的关系

目的探讨老年患者中性粒细胞/淋巴细胞比值(NLR)、转化生长因子-β1(TGF-β1)、陷窝蛋白1(Cav-1)与颅内大动脉急性闭塞机械取栓术后出血风险的关系。方法选取2017年9月—2021年12月河北中石油中心医院行颅内大动脉急性闭塞机械取栓术的老年颅内大动脉急性闭塞患者120例。根据术后是否出血分为出血组和非出血组,比较2组患者临床资料和NLR、TGF-β1、Cav-1水平差异。采用多因素Logistic回归分析评价术后出血的影响因素;采用受试者工作特征(ROC)曲线评价NLR、TGF-β1、Cav-1预测术后出血的价值。结果出血组美国国立卫生研究院卒中量表(NIHSS)评分为(19.91±2.28)分,NLR和Cav-1分别为(7.20±1.12)和(19.29±5.53)ng·mL^(-1),均高于非出血组(P<0.05);Alberta卒中项目早期电子计算机断层扫描评分(ASPECTS)评分为(5.40±0.77)分,TGF-β1为(20.20±8.28)pg·mL^(-1),均低于非出血组(P<0.05)。多因素Logistic回归分析结果显示,NIHSS评分、NLR是患者术后出血的危险因素(P<0.05),ASPECTS评分是患者术后出血的保护因素(P<0.05)。ROC曲线分析结果显示,基于ASPECTS评分、NIHSS评分、NLR建立的预测模型预测术后出血的曲线下面积为0.851,敏感性和特异性分别为64.00%和84.00%。结论NLR、Cav-1、TGF-β1均与老年患者颅内大动脉急性闭塞机械取栓术后出血有关。基于ASPECTS评分、NIHSS评分、NLR建立的预测模型在预测患者术后出血中有一定的应用价值。

干扰Gal-1通过TGF-β通路抑制人乳腺癌MDA-MB-231细胞的EMT和迁移

目的:探究干扰半乳糖凝集素1(Gal-1)通过转化生长因子β(TGF-β)途径对人乳腺癌MDA-MB-231细胞上皮-间充质转化(EMT)、迁移及增殖的影响和作用机制。方法:以shGal-1稳转细胞株和对照细胞株为材料,用Western blot检测TGF-β处理后shGal-1对MDA-MB-231细胞EMT进程的影响;通过细胞划痕实验和Transwell实验检测TGF-β处理后shGal-1对细胞迁移和侵袭的影响;用Western blot检测shGal-1对TGF-β通路蛋白的影响;用MTT实验和Western blot检测shGal-1对细胞增殖的影响。结果:shGal-1可抑制TGF-β介导的MDA-MB-231细胞EMT,并降低ERK、AKT和GSK3β的磷酸化水平,同时shGal-1可抑制MDA-MB-231细胞的迁移、侵袭和增殖。结论:shGal-1可抑制TGF-β介导的MDA-MB-231细胞EMT、迁移和增殖。

磁共振靶向成像检测心肌纤维化大鼠模型中TGF-β1表达的实验研究

目的构建载转化生长因子-β1(transforming growth factor beta-1,TGF-β1)的超小超顺磁性氧化铁(ultrasmall supperparamagnetic iron oxide,USPIO)靶向探针(USPIO-anti-TGF-β1),探究其表征及磁共振成像(magnetic resonance imaging,MRI)靶向检测大鼠心肌纤维化(myocardial fibrosis,MF)模型中TGF-β1表达的可行性。材料与方法选择40只雄性SD大鼠,其中30只采用异丙肾上腺素(isoprenaline,ISO)皮下注射法建立MF模型,另外10只作为健康对照组。通过超声评估大鼠模型建立情况。将造模成功的30只大鼠随机分为实验组、单纯对照组及空白对照组,每组10只;构建USPIO-anti-TGF-β1靶向探针,通过尾静脉注入实验组大鼠体内,单纯对照组及空白对照组分别注入相同剂量的USPIO和生理盐水,并于注射12 h后行T2序列扫描。扫描完成后取大鼠心肌标本行病理学分析。采用独立样本t检验对给药前后的MRI信号强度变化进行分析。结果MRI示实验组给药前心肌信号尚均匀,给药12 h后心内膜下心肌可见信号减低区,二者相对信号强度具有明显差异(0.72±0.12 vs.0.62±0.10,P<0.01);单纯对照组与空白对照组给药前后心肌信号未见明显减低(0.73±0.12 vs.0.71±0.12,P=0.81;0.70±0.13 vs.0.74±0.13,P=0.52)。普鲁士蓝染色显示实验组MF区域与给药后MRI所示信号减低区相符合,免疫组化可见MF区域TGF-β1的阳性表达,普鲁士蓝染色显示心肌细胞中有大量铁颗粒的沉积,证实USPIO-anti-TGF-β1靶向探针的存在。结论通过USPIO-anti-TGF-β1靶向探针进行MRI在体检测MF大鼠模型中TGF-β1的表达可行,为临床监测TGF-β1的表达及抗MF治疗方案的选择和疗效评估提供了实验依据。