Benzo[a]pyrene(B[a]P)is a food contaminant toxic for cardiovascular diseases.The nuclear translocation of Arylhydrocarbon receptor(AhR)plays an important role in B[a]P-induced oxidative stress and vascular diseases.We...Benzo[a]pyrene(B[a]P)is a food contaminant toxic for cardiovascular diseases.The nuclear translocation of Arylhydrocarbon receptor(AhR)plays an important role in B[a]P-induced oxidative stress and vascular diseases.We confi rmed that B[a]P promoted ROS production in vascular smooth muscle cells(VSMCs)in vitro and in vivo,associated with the nuclear translocation of AhR.It is known that phosphorylation inhibits while dephosphorylation of AhR promotes nuclear translocation of AhR.However,from the posttranslational modifi cation level,the mechanism by which B[a]P activates and regulates the nuclear translocation of AhR is unclear.Co-immunoprecipitation results showed that cytoplasmic AhR was phosphorylated before B[a]P stimulation,and switched to O-GlcNAcylation upon B[a]P 1-h stimulation in VSMCs,suggesting there may be a competitively inhibitory relationship between O-GlcNAcylation and phosphorylation of AhR.Next,siRNAs of O-linked N-acetylglucosamine transferase(OGT),O-GlcNAcase(OGA)and OGA inhibitor PUGNAc were used.SiOGT blocks but siOGA and PUGNAc promote B[a]P-dependent AhR nuclear translocation and oxidative stress.Ser11 may be the competitive binding site for phosphorylation and O-GlcNAcylation of AhR.Phosphorylation-mimic variant inhibits but O-GlcNAcylation of AhR promotes AhR nuclear translocation and oxidative stress.Our fi ndings highlight a new perspective for AhR nuclear translocation regulated by the competitive modifi cation between phosphorylation and O-GlcNAcylation.展开更多
Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed ...Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.展开更多
Objective: To investigate whether vascular endothelial growth factor (VEGF) gene plasmid carried by polytetra-fluoroethylene (PTFE) vascular graft materials could transfect endothelial cells (ECs) and promote their gr...Objective: To investigate whether vascular endothelial growth factor (VEGF) gene plasmid carried by polytetra-fluoroethylene (PTFE) vascular graft materials could transfect endothelial cells (ECs) and promote their growth. Methods: PTFE vascular graft materials carried with pCDI-hVEGF121, pCDI or pEGFP were incubated in Tris-buffer solution and the values of optical density of 260 nm at different time were plotted, then the DNA controlled release curve was made. ECs derived from human umbilical vein were seeded on the pCDI-hVEGF121/pCDI/pEGFP-PTFE materials or tissue culture plates, ECs numbers were counted and VEGF protein concentrations at different time were measured by enzyme-linked immunoadsorbent assay method. Green fluorescent protein (GFP) expression in ECs on pEGFP-PTFE materials was examined with fluorescence mi-croscopy. Results: The controlled release curve showed that the gene released from PTFE materials was rapid within 8 h, then slowed down and that the gene released continuously even after 72 h. At 24, 72 and 120 h, ECs number and proliferation rate of pCDI-hVEGF121-PTFE materials were higher than those of pCDI or pEGFP-PTFE materials (P<0.05). VEGF protein concentra-tion of pCDI-hVEGF121-PTFE materials was higher than that of pCDI or pEGFP-PTFE materials at 6, 24, 72 and 120 h (P<0.01). GFP expression in ECs on the pEGFP-PTFE materials could be detected by fluorescence microscopy. Conclusion: PTFE graft can be used as a carrier of VEGF gene plasmid, VEGF gene carried by PTFE can transfect ECs and promote ECs growth.展开更多
Pulmonary hypertension(PH)is a severe and progressive disease characterized by increased pulmonary vascular resistance leading to right heart failure and death.In PH,the cellular metabolisms including those of the thr...Pulmonary hypertension(PH)is a severe and progressive disease characterized by increased pulmonary vascular resistance leading to right heart failure and death.In PH,the cellular metabolisms including those of the three major nutrients(carbohydrate,lipid and protein)are aberrant in pulmonary vascular cells.Glucose uptake,glycolysis,insulin resistance,sphingolipid S1P,PGE2,TXA2,leukotrienes and glutaminolysis are upregulated,and phospholipid-prostacyclin and L-arginine-nitric oxide pathway are compromised in lung vascular cells.Fatty acid metabolism is disordered in lung endothelial cells and smooth muscle cells.These molecular mechanisms are integrated to promote PH-specific abnormal vascular cell proliferation and vascular remodeling.This review summarizes the recent advances in the metabolic reprogramming of glucose,fatty acid,and amino acid metabolism in pulmonary vascular remodeling in PH and the mechanisms for how these alterations affect vascular cell fate and impact the course of PH.展开更多
Objectives To investigate the effects of testosterone enanthate (TE) on serum lip- ids and lipoproteins metabolism and the expression of androgen receptor (AR) , estrogen receptor beta ( ER - β) and platelet derived ...Objectives To investigate the effects of testosterone enanthate (TE) on serum lip- ids and lipoproteins metabolism and the expression of androgen receptor (AR) , estrogen receptor beta ( ER - β) and platelet derived growth factor beta ( PDGFR - β) in aortic vascular smooth muscle tissues (VSMTs). Methods Forty aged male rats were ran- domly divided into 4 groups, group A (placebo group) , group B (2. 5 mg/kg intramuscular injection of TE once a week ) , group C (5.0 mg/kg intramuscular injection of TE once a week ) , group D ( 10. 0 mg/kg intramus- cular injection of TE once a week). All animals were fed freely during 16 - week treatment periods. The ex- pression of AR ,ER - βand PDGFR - β were studied by Western bolt. Results Average serum LDL - C was lower in group D than that in group A ( p < 0. 01 ). Compared with the other groups, average serum TC was also lower in group D (p <0. 05). AR expression in aortic vascular smooth muscle tissues could be regulated by TE: 99.50 ±21.74, 125.38 ±28.68 and 101.98 ± 15.42 for TE concentrations at 2.5 mg/kg, 5.0 mg/kg and 10.0 mg/kg, respectively , the expression of ER - β could be regulated by TE: 92. 34 ± 18. 68, 47. 72 ± 18.12, 82.13 ±23.50, and the expression of PDGFR - β could be regulated as well by TE: 219.70 ±45. 59, 50.16 ±9. 72, 125.36 ±15. 74(Data for AR ,ER-β and PDGFR - β protein band intensity were expressed with x ± s, with control group taken as 100 ).Conclusions This study indicates that androgens have significant effects on serum lipids and lipoprotein metabolism. Testosterone enanthate at 5. 0 mg/kg can stimulate the expression of AR, but inhibite the expres- sion of PDGFR. Testosterone enanthate at the concen- trations of 5. 0 mg/kg and 10. 0 mg/kg can inhibite the expression of ER - β.展开更多
Objective To study the effects of estrogen level and cholesterol - rich diet on the expression of estrogen receptor (ER) in cardiovascular tissues including vascular endothelial cells (VEC) of female rats. Methods...Objective To study the effects of estrogen level and cholesterol - rich diet on the expression of estrogen receptor (ER) in cardiovascular tissues including vascular endothelial cells (VEC) of female rats. Methods The receptor binding assay (RBA) was adopted to measure the estrogen receptor level in aortic wall, heart and vascular endothelial cells of female rats on a cholesterol - rich diet. A radioimmunoassay was employed to measure the level of serum estradiol. Results The number of ER significantly decreased in hearts, aorta and vascular endothelial cells in the ovariectomized rats and the rats on a cholesterol- rich diet. In contrast, the adminis-tration of estrogen somewhat restored the expression of ER. Conclusions For female rats, the level of estrogen affects the expression of ER in cardiovascular system. The number of ER decreases along with the decrease in the level of estrogen. A cholesterol -rich diet also can decrease the expression of ER in cardio-vascular system of female rats.展开更多
Objectives To ob-serve the effect of different estrogen levels on the secretory function of vascular endothelial cells of female rats, and study the effect of modulation of estrogen level on the expression of vascular...Objectives To ob-serve the effect of different estrogen levels on the secretory function of vascular endothelial cells of female rats, and study the effect of modulation of estrogen level on the expression of vascular cell adhesion molecule - 1 and the concentration of estrogen receptor in vascular endothelial cells. Methods Radioim-munology was used to measure the serum concentration of endothelin and PGI2, and copper - cadmium reduction was employed to measure the serum content of nitrogen monoxide. Radioligand binding and flowcy-tometry were used to measure the expression of estrogen receptor and vascular cell adhesion molecule (VCAM - 1) of vascular endothelial cells respectively. Results 1. The serum concentration of nitric oxide and PGI2 decreased when the ovaries of female rats were removed. In ovariectomized rats, given estrogen, the concentration rose ( P 【 0. 05), but the plasma concentration of endothelin was adverse to it. 2. The concentration of estrogen receptor of vascular endothelial展开更多
Exosome-derived long non-coding RNAs(lncRNAs)are extensively engaged in recovery and repair of the injured spinal cord,through different mechanisms.However,to date no study has systematically evaluated the differentia...Exosome-derived long non-coding RNAs(lncRNAs)are extensively engaged in recovery and repair of the injured spinal cord,through different mechanisms.However,to date no study has systematically evaluated the differentially expressed lncRNAs involved in the development of spinal cord injury.Thus,the aim of this study was to identify key circulating exosome-derived lncRNAs in a rat model of spinal cord injury and investigate their potential actions.To this end,we established a rat model of spinal cord hemisection.Circulating exosomes were extracted from blood samples from spinal cord injury and control(sham)rats and further identified through Western blotting and electron microscopy.RNA was isolated from the exosomes and sequenced.The enrichment analysis demonstrated that there were distinctively different lncRNA and mRNA expression patterns between the two groups.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)functional analysis were performed to determine the possible involvements of upregulated and downregulated lncRNAs in various pathways and different biological processes,as well as their cellular locations and molecular functions.Furthermore,quantitative reverse transcription-polymerase chain reaction showed that the expression of five lncRNAs––ENSRN0T00000067908,XR_590093,XR_591455,XR_360081,and XR_346933––was increased,whereas the expression of XR_351404,XR_591426,XR_353833,XR_590076,and XR_590719 was decreased.Of note,these 10 lncRNAs were at the center of the lncRNA-miRNA-mRNA coexpression network,which also included 198 mRNAs and 41 miRNAs.Taken together,our findings show that several circulating exosomal lncRNAs are differentially expressed after spinal cord injury,suggesting that they may be involved in spinal cord injury pathology and pathogenesis.These lncRNAs could potentially serve as targets for the clinical diagnosis and treatment of spinal cord injury.展开更多
Obiective:To investigate the effects of Xiaoxianxiong Tang on the proliferation,invasion,apoptosis,and other cell biological behaviors of non-small cell lung cancer A549 cells.Methods:Human lung adenocarcinoma A549 ce...Obiective:To investigate the effects of Xiaoxianxiong Tang on the proliferation,invasion,apoptosis,and other cell biological behaviors of non-small cell lung cancer A549 cells.Methods:Human lung adenocarcinoma A549 cells were cultured in vitro,and the IC50 concentration and effective time of administration of Xiaoxianxiong Tang were determined by the CCK-8 assay to detect the inhibitory effect of Xiaoxianxiong Tang on A549 cells proliferation.The effect of the Xiaoxianxiong Tang on apoptosis was determined by flow cytometry;the apoptosis-related protein was detected via Western blot;the metastasis-related protein mRNA was detected by RT-PCR.Results:Xiaoxianxiong Tang significantly inhibited the proliferation viability,the invasive ability,and the clonogenic ability of A549 cells compared with the control group(P<0.001).Moreover,Xiaoxianxiong Tang significantly promoted the apoptosis of A549 cells(P<0.001).Xiaoxianxiong Tang significantly up-regulated Bax and down-regulated Bcl2 expression in A549 cells compared with the control group(P<0.01).The mRNA expression of MMP2 and MMP9 was significantly down-regulated by Xiaoxianxiong Tang compared with the control group(P<0.05).Conclusion:Xiaoxianxiong Tang has the effect of regulating the biological behavior of A549 cells,and Xiaoxianxiong Tang significantly inhibites the proliferation viability,colony formation,and invasion ability of lung cancer A549 cells.展开更多
AIM To evaluate the diagnostic and prognostic value of presepsin in cirrhosis-associated bacterial infections. METHODS Two hundred and sixteen patients with cirrhosis were enrolled. At admission, the presence of bacte...AIM To evaluate the diagnostic and prognostic value of presepsin in cirrhosis-associated bacterial infections. METHODS Two hundred and sixteen patients with cirrhosis were enrolled. At admission, the presence of bacterial infections and level of plasma presepsin, serum C-reactive protein(CRP) and procalcitonin(PCT) were evaluated. Patients were followed for three months to assess the possible association between presepsin level and short-term mortality.RESULTS Present 34.7 of patients had bacterial infection. Presepsin levels were significantly higher in patients with infection than without(median, 1002 pg/m L vs 477 pg/m L, P < 0.001), increasing with the severity of infection [organ failure(OF): Yes vs No, 2358 pg/m L vs 710 pg/m L, P < 0.001]. Diagnostic accuracy of presepsin for severe infections was similar to PCT and superior to CRP(AUC-ROC: 0.85, 0.85 and 0.66, respectively, P = NS for presepsin vs PCT and P < 0.01 for presepsin vs CRP). At the optimal cut-off value of presepsin > 1206 pg/m L sensitivity, specificity, positive predictive values and negative predictive values were as follows: 87.5%, 74.5%, 61.8% and 92.7%. The accuracy of presepsin, however, decreased in advanced stage of the disease or in the presence of renal failure, most probably because of the significantly elevated presepsin levels in non-infected patients. 28-d mortality rate was higher among patients with > 1277 pg/m L compared to those with ≤ 1277 pg/m L(46.9% vs 11.6%, P < 0.001). In a binary logistic regression analysis, however, only PCT(OR = 1.81, 95%CI: 1.09-3.01, P = 0.022) but neither presepsin nor CRP were independent risk factor for 28-d mortality after adjusting with MELD score and leukocyte count.CONCLUSION Presepsin is a valuable new biomarker for defining severe infections in cirrhosis, proving same efficacy as PCT. However, it is not a useful marker of short-term mortality.展开更多
AIM:To investigate the anti-hepatofibrotic effects of Gardenia jasminoides in liver fibrosis.METHODS:Male Sprague-Dawley rats underwent common bile duct ligation(BDL) for 14 d and were treated with Gardenia jasminoide...AIM:To investigate the anti-hepatofibrotic effects of Gardenia jasminoides in liver fibrosis.METHODS:Male Sprague-Dawley rats underwent common bile duct ligation(BDL) for 14 d and were treated with Gardenia jasminoides by gavage.The ef-fects of Gardenia jasminoides on liver fibrosis and the detailed molecular mechanisms were also assessed in human hepatic stellate cells(LX-2) in vitro.RESULTS:Treatment with Gardenia jasminoides decreased serum alanine aminotransferase(BDL vs BDL + 100 mg/kg Gardenia jasminoides,146.6 ± 15 U/L vs 77 ± 6.5 U/L,P = 0.0007) and aspartate aminotransferase(BDL vs BDL + 100 mg/kg Gardenia jasminoides,188 ± 35.2 U/L vs 128 ± 19 U/L,P = 0.005) as well as hydroxyproline(BDL vs BDL + 100 mg/kg Gardenia jasminoides,438 ± 40.2 μg/g vs 228 ± 10.3 μg/g liver tissue,P = 0.004) after BDL.Furthermore,Gardenia jasminoides significantly reduced liver mRNA and/or protein expression of transforming growth factor β1(TGF-β1),collagen type?Ⅰ?(Col?Ⅰ) and α-smooth muscle actin(α-SMA).Gardenia jasminoides significantly suppressed the upregulation of TGF-β1,Col?Ⅰand α-SMA in LX-2 exposed to recombinant TGF-β1.Moreover,Gardenia jasminoides inhibited TGF-β1-induced Smad2 phosphorylation in LX-2 cells.CONCLUSION:Gardenia jasminoides exerts antifibrotic effects in the liver fibrosis and may represent a novel antifibrotic agent.展开更多
Objective: To observe the changes of coagulation and fibrinolysis function in human umbilical cord vein endothelial cells (HUVEC) induced by recombinant human tumor necrosis factor-a (rhTNF-α) and the effect of Naota...Objective: To observe the changes of coagulation and fibrinolysis function in human umbilical cord vein endothelial cells (HUVEC) induced by recombinant human tumor necrosis factor-a (rhTNF-α) and the effect of Naotaifang extract (脑泰方, NTE) on it. Methods: Cultured HUVEC is randomly divided into six groups: Control group, NTE control group (only 2 g/L NTE), rhTNF-α group (100μg/L rhTNF-α), and low-dosage, middle-dosage and high-dosage NTE group (100μg/L rhTNF-α and 0. 67g/L, 2 g/L, 6 g/L NTE). The coagulation activity of frozen-dissolved HUVEC, yon Willebrand factor(vWF) content in the conditioned medium and tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI) activity were to be detected after 24 hrs. Results: Compared with the control group, PAI activity were enhanced, vWF release markedly increased in conditioned medium of TNF-α group (P<0. 01) and the frozen-dissolved HUVEC markedly shortens the rabbit plasma prothrombin time, and the above changes could be significantly inhibited by the 3 dosages of NTE (P<0. 05, P<0.01). Conclusion: NTE is effective in inhibiting the coagulation activity of the HUVEC non-stimulated or stimulated by rhTNF-α to enhance the vWF release, and to adjust fibrinolytic function, and mainly to inhibit the PAI activity.展开更多
The mineralocorticoid receptor(MR),well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis,has aldosterone as one of its main agonists.Much research in the last...The mineralocorticoid receptor(MR),well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis,has aldosterone as one of its main agonists.Much research in the last 10–15 years indicates that MRs are also expressed outside of the kidney,including in the brain,vasculature and heart,where they contribute to the pathophysiology of disease(Dinh et al.,2012;展开更多
The biological features of most foamy viruses(FVs) are poorly understood, including bovine foamy virus(BFV). BFV strain 3026(BFV3026) was isolated from the peripheral blood mononuclear cells of an infected cow in Zhan...The biological features of most foamy viruses(FVs) are poorly understood, including bovine foamy virus(BFV). BFV strain 3026(BFV3026) was isolated from the peripheral blood mononuclear cells of an infected cow in Zhangjiakou, China. A full-length genomic clone of BFV3026 was obtained from BFV3026-infected cells, and it exhibited more than 99% amino acid(AA) homology to another BFV strain isolated in the USA. Upon transfection into fetal canine thymus cells, the full-length BFV3026 clone produced viral structural and auxiliary proteins, typical cytopathic effects, and virus particles. These results demonstrate that the full-length BFV3026 clone is fully infectious and can be used in further BFV3026 research.展开更多
We aim to provide an up-to-date summary of infantile hepatic hemangioma(IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver.Eligible peer-reviewed article...We aim to provide an up-to-date summary of infantile hepatic hemangioma(IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver.Eligible peer-reviewed articles on hepatic infantile hemangiomas,published between 2000 and 2015,were reviewed for this study.IHH is the most common hepatic vascular tumor in children.Once a liver mass is identified in an infant,the differential diagnosis ranges from vascular malformations to benign and malignant tumors including mesenchymal hamartoma,hepatoblastoma,metastatic neuroblastoma,so careful physical examination,imaging studies,and,if indicated,tumor markers and biopsy,are of pivotal importance to ascertain the correct diagnosis.Despite the benign nature of IHHs,some of these lesions may demand medical and/or surgical intervention,especially for multiple and diffuse IHH.Complications can include hepatomegaly,hypothyroidism and cardiac failure.Therefore,a close follow-up is required until complete involution of the lesions.We propose an algorithm to guide the physicians towards the proper management of hepatic lesions.展开更多
Recent advances in the management of lupus nephritis,together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy,have contributed to a favorable outcome in children and adolescents wit...Recent advances in the management of lupus nephritis,together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy,have contributed to a favorable outcome in children and adolescents with systemic lupus erythematosus(SLE).Nevertheless,we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis.Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are reviewed.Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide(IVCY)are effective for preserving renal function in adult patients,CPA is a potent immunosuppressive agent that induces severe toxicity,including myelo-and gonadal toxicity,and increases the risk of secondary malignancy.Thus,treatment for controlling lupus nephritis activity,especially in children and adolescents,remains challenging.Cyclosporine A(Cs A)and tacrolimus(Tac)are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells,thereby inhibiting thetranscription of the early activation genes of interleukin(IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-α,IL-1βand IL-6.Therefore,both drugs,which we believe may be less cytotoxic,are attractive therapeutic options for young patients with lupus nephritis.Recently,a multidrug regimen of prednisolone(PDN),Tac,and mycophenolate mofetile(MMF)has been found effective and relatively safe in adult lupus nephritis.Since the mechanisms of action of MMF and Tac are probably complementary,multidrug therapy for lupus nephritis may be useful.We propose as an alternative to IVCY,a multidrug therapy with mizoribine,which acts very similarly to MMF,and Tac,which has a different mode of action,combined with PDN for pediatric-onset lupus nephritis.We also believe that a multidrug therapy including Cs A and Tac may be an attractive option for young patients with SLE and lupus展开更多
基金supported by the National Key Research Project of China(2022YFF1100300)National Natural Science Foundation of China(32272328)+5 种基金Natural Science Foundation of Hebei Province(B2022321001)Major Public Welfare Projects in Henan Province(201300110200)National Key Research Project of Hebei Province(20375502D)National Key Research Project of Hebei Province(H2021206427)University Science and Technology Research Project of Hebei Province(QN2017107)Postdoctoral Research Funds of Hebei Medical University(307050100163759).
文摘Benzo[a]pyrene(B[a]P)is a food contaminant toxic for cardiovascular diseases.The nuclear translocation of Arylhydrocarbon receptor(AhR)plays an important role in B[a]P-induced oxidative stress and vascular diseases.We confi rmed that B[a]P promoted ROS production in vascular smooth muscle cells(VSMCs)in vitro and in vivo,associated with the nuclear translocation of AhR.It is known that phosphorylation inhibits while dephosphorylation of AhR promotes nuclear translocation of AhR.However,from the posttranslational modifi cation level,the mechanism by which B[a]P activates and regulates the nuclear translocation of AhR is unclear.Co-immunoprecipitation results showed that cytoplasmic AhR was phosphorylated before B[a]P stimulation,and switched to O-GlcNAcylation upon B[a]P 1-h stimulation in VSMCs,suggesting there may be a competitively inhibitory relationship between O-GlcNAcylation and phosphorylation of AhR.Next,siRNAs of O-linked N-acetylglucosamine transferase(OGT),O-GlcNAcase(OGA)and OGA inhibitor PUGNAc were used.SiOGT blocks but siOGA and PUGNAc promote B[a]P-dependent AhR nuclear translocation and oxidative stress.Ser11 may be the competitive binding site for phosphorylation and O-GlcNAcylation of AhR.Phosphorylation-mimic variant inhibits but O-GlcNAcylation of AhR promotes AhR nuclear translocation and oxidative stress.Our fi ndings highlight a new perspective for AhR nuclear translocation regulated by the competitive modifi cation between phosphorylation and O-GlcNAcylation.
基金supported by the Postdoctoral Research Funds of Hebei Medical University(30705010016-3759)Natural Science Foundation of China(32272328)+4 种基金Natural Science Foundation of Hebei Province(B2022321001)National Key Research Project of Hebei Province(20375502D)Postdoctoral Research Project of Hebei Province(B2022003031)Science and Technology Research Program of Hebei Provincial Colleges(QN2023229)Hebei Provincial Key Laboratory of Nutrition and Health(2023YDYY-KF05)。
文摘Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.
基金We are grateful to Dr Guan KL （Moore＇s Cancer Center, La Jolla, CA, USA） for the gift of pCMV-MEKca. This study was supported by the National Natural Science Foundation of China （30770787 and 90919035）, the National Basic Research Program of China （2005CB523301）, and the International Cooperation in Science and Technology Projects （2006DFB32460） and the Hebei Province Natural Science Foundation （C2007000831）.
基金Project supported by the Science and Technology Research Foun-dation of Zhejiang Province, China (No. 991110052) and the Re-search and Development Funds of the Second Affiliated Hospital, School of Medicine, Zhejiang University, China
文摘Objective: To investigate whether vascular endothelial growth factor (VEGF) gene plasmid carried by polytetra-fluoroethylene (PTFE) vascular graft materials could transfect endothelial cells (ECs) and promote their growth. Methods: PTFE vascular graft materials carried with pCDI-hVEGF121, pCDI or pEGFP were incubated in Tris-buffer solution and the values of optical density of 260 nm at different time were plotted, then the DNA controlled release curve was made. ECs derived from human umbilical vein were seeded on the pCDI-hVEGF121/pCDI/pEGFP-PTFE materials or tissue culture plates, ECs numbers were counted and VEGF protein concentrations at different time were measured by enzyme-linked immunoadsorbent assay method. Green fluorescent protein (GFP) expression in ECs on pEGFP-PTFE materials was examined with fluorescence mi-croscopy. Results: The controlled release curve showed that the gene released from PTFE materials was rapid within 8 h, then slowed down and that the gene released continuously even after 72 h. At 24, 72 and 120 h, ECs number and proliferation rate of pCDI-hVEGF121-PTFE materials were higher than those of pCDI or pEGFP-PTFE materials (P<0.05). VEGF protein concentra-tion of pCDI-hVEGF121-PTFE materials was higher than that of pCDI or pEGFP-PTFE materials at 6, 24, 72 and 120 h (P<0.01). GFP expression in ECs on the pEGFP-PTFE materials could be detected by fluorescence microscopy. Conclusion: PTFE graft can be used as a carrier of VEGF gene plasmid, VEGF gene carried by PTFE can transfect ECs and promote ECs growth.
基金This work was supported by NIH/NHLBI R01 HL134934,VA Merit Review Award BX002035,and Flight Attendants Medical Research Institute grant 140083_CIA.
文摘Pulmonary hypertension(PH)is a severe and progressive disease characterized by increased pulmonary vascular resistance leading to right heart failure and death.In PH,the cellular metabolisms including those of the three major nutrients(carbohydrate,lipid and protein)are aberrant in pulmonary vascular cells.Glucose uptake,glycolysis,insulin resistance,sphingolipid S1P,PGE2,TXA2,leukotrienes and glutaminolysis are upregulated,and phospholipid-prostacyclin and L-arginine-nitric oxide pathway are compromised in lung vascular cells.Fatty acid metabolism is disordered in lung endothelial cells and smooth muscle cells.These molecular mechanisms are integrated to promote PH-specific abnormal vascular cell proliferation and vascular remodeling.This review summarizes the recent advances in the metabolic reprogramming of glucose,fatty acid,and amino acid metabolism in pulmonary vascular remodeling in PH and the mechanisms for how these alterations affect vascular cell fate and impact the course of PH.
文摘Objectives To investigate the effects of testosterone enanthate (TE) on serum lip- ids and lipoproteins metabolism and the expression of androgen receptor (AR) , estrogen receptor beta ( ER - β) and platelet derived growth factor beta ( PDGFR - β) in aortic vascular smooth muscle tissues (VSMTs). Methods Forty aged male rats were ran- domly divided into 4 groups, group A (placebo group) , group B (2. 5 mg/kg intramuscular injection of TE once a week ) , group C (5.0 mg/kg intramuscular injection of TE once a week ) , group D ( 10. 0 mg/kg intramus- cular injection of TE once a week). All animals were fed freely during 16 - week treatment periods. The ex- pression of AR ,ER - βand PDGFR - β were studied by Western bolt. Results Average serum LDL - C was lower in group D than that in group A ( p < 0. 01 ). Compared with the other groups, average serum TC was also lower in group D (p <0. 05). AR expression in aortic vascular smooth muscle tissues could be regulated by TE: 99.50 ±21.74, 125.38 ±28.68 and 101.98 ± 15.42 for TE concentrations at 2.5 mg/kg, 5.0 mg/kg and 10.0 mg/kg, respectively , the expression of ER - β could be regulated by TE: 92. 34 ± 18. 68, 47. 72 ± 18.12, 82.13 ±23.50, and the expression of PDGFR - β could be regulated as well by TE: 219.70 ±45. 59, 50.16 ±9. 72, 125.36 ±15. 74(Data for AR ,ER-β and PDGFR - β protein band intensity were expressed with x ± s, with control group taken as 100 ).Conclusions This study indicates that androgens have significant effects on serum lipids and lipoprotein metabolism. Testosterone enanthate at 5. 0 mg/kg can stimulate the expression of AR, but inhibite the expres- sion of PDGFR. Testosterone enanthate at the concen- trations of 5. 0 mg/kg and 10. 0 mg/kg can inhibite the expression of ER - β.
文摘Objective To study the effects of estrogen level and cholesterol - rich diet on the expression of estrogen receptor (ER) in cardiovascular tissues including vascular endothelial cells (VEC) of female rats. Methods The receptor binding assay (RBA) was adopted to measure the estrogen receptor level in aortic wall, heart and vascular endothelial cells of female rats on a cholesterol - rich diet. A radioimmunoassay was employed to measure the level of serum estradiol. Results The number of ER significantly decreased in hearts, aorta and vascular endothelial cells in the ovariectomized rats and the rats on a cholesterol- rich diet. In contrast, the adminis-tration of estrogen somewhat restored the expression of ER. Conclusions For female rats, the level of estrogen affects the expression of ER in cardiovascular system. The number of ER decreases along with the decrease in the level of estrogen. A cholesterol -rich diet also can decrease the expression of ER in cardio-vascular system of female rats.
文摘Objectives To ob-serve the effect of different estrogen levels on the secretory function of vascular endothelial cells of female rats, and study the effect of modulation of estrogen level on the expression of vascular cell adhesion molecule - 1 and the concentration of estrogen receptor in vascular endothelial cells. Methods Radioim-munology was used to measure the serum concentration of endothelin and PGI2, and copper - cadmium reduction was employed to measure the serum content of nitrogen monoxide. Radioligand binding and flowcy-tometry were used to measure the expression of estrogen receptor and vascular cell adhesion molecule (VCAM - 1) of vascular endothelial cells respectively. Results 1. The serum concentration of nitric oxide and PGI2 decreased when the ovaries of female rats were removed. In ovariectomized rats, given estrogen, the concentration rose ( P 【 0. 05), but the plasma concentration of endothelin was adverse to it. 2. The concentration of estrogen receptor of vascular endothelial
文摘Exosome-derived long non-coding RNAs(lncRNAs)are extensively engaged in recovery and repair of the injured spinal cord,through different mechanisms.However,to date no study has systematically evaluated the differentially expressed lncRNAs involved in the development of spinal cord injury.Thus,the aim of this study was to identify key circulating exosome-derived lncRNAs in a rat model of spinal cord injury and investigate their potential actions.To this end,we established a rat model of spinal cord hemisection.Circulating exosomes were extracted from blood samples from spinal cord injury and control(sham)rats and further identified through Western blotting and electron microscopy.RNA was isolated from the exosomes and sequenced.The enrichment analysis demonstrated that there were distinctively different lncRNA and mRNA expression patterns between the two groups.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)functional analysis were performed to determine the possible involvements of upregulated and downregulated lncRNAs in various pathways and different biological processes,as well as their cellular locations and molecular functions.Furthermore,quantitative reverse transcription-polymerase chain reaction showed that the expression of five lncRNAs––ENSRN0T00000067908,XR_590093,XR_591455,XR_360081,and XR_346933––was increased,whereas the expression of XR_351404,XR_591426,XR_353833,XR_590076,and XR_590719 was decreased.Of note,these 10 lncRNAs were at the center of the lncRNA-miRNA-mRNA coexpression network,which also included 198 mRNAs and 41 miRNAs.Taken together,our findings show that several circulating exosomal lncRNAs are differentially expressed after spinal cord injury,suggesting that they may be involved in spinal cord injury pathology and pathogenesis.These lncRNAs could potentially serve as targets for the clinical diagnosis and treatment of spinal cord injury.
基金Natural Science Foundation of Hunan Province(2021JJ30017)Key Project of Traditional Chinese Medicine Research Program of Hunan Province(C2022001)+1 种基金Key Project of Education Department of Hunan Province(21A0226)Changsha City Natural Science Foundation Project(kq2208184)。
文摘Obiective:To investigate the effects of Xiaoxianxiong Tang on the proliferation,invasion,apoptosis,and other cell biological behaviors of non-small cell lung cancer A549 cells.Methods:Human lung adenocarcinoma A549 cells were cultured in vitro,and the IC50 concentration and effective time of administration of Xiaoxianxiong Tang were determined by the CCK-8 assay to detect the inhibitory effect of Xiaoxianxiong Tang on A549 cells proliferation.The effect of the Xiaoxianxiong Tang on apoptosis was determined by flow cytometry;the apoptosis-related protein was detected via Western blot;the metastasis-related protein mRNA was detected by RT-PCR.Results:Xiaoxianxiong Tang significantly inhibited the proliferation viability,the invasive ability,and the clonogenic ability of A549 cells compared with the control group(P<0.001).Moreover,Xiaoxianxiong Tang significantly promoted the apoptosis of A549 cells(P<0.001).Xiaoxianxiong Tang significantly up-regulated Bax and down-regulated Bcl2 expression in A549 cells compared with the control group(P<0.01).The mRNA expression of MMP2 and MMP9 was significantly down-regulated by Xiaoxianxiong Tang compared with the control group(P<0.05).Conclusion:Xiaoxianxiong Tang has the effect of regulating the biological behavior of A549 cells,and Xiaoxianxiong Tang significantly inhibites the proliferation viability,colony formation,and invasion ability of lung cancer A549 cells.
基金Supported by János Bólyai Research Scholarship of Hungarian Academy of Sciences,No.BO/00426/11University of Debrecen and Research Grant of National Research,No.RH/885/2013Development and Innovation Office,No.K115818/2015/1
文摘AIM To evaluate the diagnostic and prognostic value of presepsin in cirrhosis-associated bacterial infections. METHODS Two hundred and sixteen patients with cirrhosis were enrolled. At admission, the presence of bacterial infections and level of plasma presepsin, serum C-reactive protein(CRP) and procalcitonin(PCT) were evaluated. Patients were followed for three months to assess the possible association between presepsin level and short-term mortality.RESULTS Present 34.7 of patients had bacterial infection. Presepsin levels were significantly higher in patients with infection than without(median, 1002 pg/m L vs 477 pg/m L, P < 0.001), increasing with the severity of infection [organ failure(OF): Yes vs No, 2358 pg/m L vs 710 pg/m L, P < 0.001]. Diagnostic accuracy of presepsin for severe infections was similar to PCT and superior to CRP(AUC-ROC: 0.85, 0.85 and 0.66, respectively, P = NS for presepsin vs PCT and P < 0.01 for presepsin vs CRP). At the optimal cut-off value of presepsin > 1206 pg/m L sensitivity, specificity, positive predictive values and negative predictive values were as follows: 87.5%, 74.5%, 61.8% and 92.7%. The accuracy of presepsin, however, decreased in advanced stage of the disease or in the presence of renal failure, most probably because of the significantly elevated presepsin levels in non-infected patients. 28-d mortality rate was higher among patients with > 1277 pg/m L compared to those with ≤ 1277 pg/m L(46.9% vs 11.6%, P < 0.001). In a binary logistic regression analysis, however, only PCT(OR = 1.81, 95%CI: 1.09-3.01, P = 0.022) but neither presepsin nor CRP were independent risk factor for 28-d mortality after adjusting with MELD score and leukocyte count.CONCLUSION Presepsin is a valuable new biomarker for defining severe infections in cirrhosis, proving same efficacy as PCT. However, it is not a useful marker of short-term mortality.
基金Acknowledgments We thank Dr Lena Claesson-Welsh （Uppsala University）, and PIs of Model Animal Research Center （MARC, Nanjing University） for the helpful discussion about the work, and Yanlan Cao, Wenting Shi and all the staff in the MARC Animal facility of Nanjing University for excellent technical assistance. This work wasfinancially supported by grants from the National Natural Science Foundation of China （30771069, 30671038, and 30930028）, the Ministry of Science and Technology of China （2006CB943500）, and the Ministry of Education of China （NCET： Program for New Century Excellent Talents in University）.
基金Supported by The Natural Science Foundation of China,No.81170450 to Lu MQ and No.81200308 to Lan TThe PhD Start-up Fund of Natural Science Foundation of Guangdong Province,China,No.S2012040008026The New Star of Science and Technology Foundation of Zhu Jiang in Guangzhou City
文摘AIM:To investigate the anti-hepatofibrotic effects of Gardenia jasminoides in liver fibrosis.METHODS:Male Sprague-Dawley rats underwent common bile duct ligation(BDL) for 14 d and were treated with Gardenia jasminoides by gavage.The ef-fects of Gardenia jasminoides on liver fibrosis and the detailed molecular mechanisms were also assessed in human hepatic stellate cells(LX-2) in vitro.RESULTS:Treatment with Gardenia jasminoides decreased serum alanine aminotransferase(BDL vs BDL + 100 mg/kg Gardenia jasminoides,146.6 ± 15 U/L vs 77 ± 6.5 U/L,P = 0.0007) and aspartate aminotransferase(BDL vs BDL + 100 mg/kg Gardenia jasminoides,188 ± 35.2 U/L vs 128 ± 19 U/L,P = 0.005) as well as hydroxyproline(BDL vs BDL + 100 mg/kg Gardenia jasminoides,438 ± 40.2 μg/g vs 228 ± 10.3 μg/g liver tissue,P = 0.004) after BDL.Furthermore,Gardenia jasminoides significantly reduced liver mRNA and/or protein expression of transforming growth factor β1(TGF-β1),collagen type?Ⅰ?(Col?Ⅰ) and α-smooth muscle actin(α-SMA).Gardenia jasminoides significantly suppressed the upregulation of TGF-β1,Col?Ⅰand α-SMA in LX-2 exposed to recombinant TGF-β1.Moreover,Gardenia jasminoides inhibited TGF-β1-induced Smad2 phosphorylation in LX-2 cells.CONCLUSION:Gardenia jasminoides exerts antifibrotic effects in the liver fibrosis and may represent a novel antifibrotic agent.
基金The item is supported by Natural Science Foundation of Hunan Province (No. 98JJY 2027)Young-middle Aged Science and Technological Fund of Hunan Province (NO.00JZYZ145)
文摘Objective: To observe the changes of coagulation and fibrinolysis function in human umbilical cord vein endothelial cells (HUVEC) induced by recombinant human tumor necrosis factor-a (rhTNF-α) and the effect of Naotaifang extract (脑泰方, NTE) on it. Methods: Cultured HUVEC is randomly divided into six groups: Control group, NTE control group (only 2 g/L NTE), rhTNF-α group (100μg/L rhTNF-α), and low-dosage, middle-dosage and high-dosage NTE group (100μg/L rhTNF-α and 0. 67g/L, 2 g/L, 6 g/L NTE). The coagulation activity of frozen-dissolved HUVEC, yon Willebrand factor(vWF) content in the conditioned medium and tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI) activity were to be detected after 24 hrs. Results: Compared with the control group, PAI activity were enhanced, vWF release markedly increased in conditioned medium of TNF-α group (P<0. 01) and the frozen-dissolved HUVEC markedly shortens the rabbit plasma prothrombin time, and the above changes could be significantly inhibited by the 3 dosages of NTE (P<0. 05, P<0.01). Conclusion: NTE is effective in inhibiting the coagulation activity of the HUVEC non-stimulated or stimulated by rhTNF-α to enhance the vWF release, and to adjust fibrinolytic function, and mainly to inhibit the PAI activity.
基金supported by a postdoctoral fellowship from the National Health and Medical Research Council (NHMRC) of Australiathe Foundation for High Blood Pressure Research Australia (to SC)grants from the NHMRC and the National Heart Foundation of Australia
文摘The mineralocorticoid receptor(MR),well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis,has aldosterone as one of its main agonists.Much research in the last 10–15 years indicates that MRs are also expressed outside of the kidney,including in the brain,vasculature and heart,where they contribute to the pathophysiology of disease(Dinh et al.,2012;
基金supported by grants from the National Natural Science Foundation of China (31070135, 31370182)the Tianjin Research Program of Application Foundation and Advanced Technology (12JCQNJC06100)New Century Excellent Talents in University (NCET-10-0508)
文摘The biological features of most foamy viruses(FVs) are poorly understood, including bovine foamy virus(BFV). BFV strain 3026(BFV3026) was isolated from the peripheral blood mononuclear cells of an infected cow in Zhangjiakou, China. A full-length genomic clone of BFV3026 was obtained from BFV3026-infected cells, and it exhibited more than 99% amino acid(AA) homology to another BFV strain isolated in the USA. Upon transfection into fetal canine thymus cells, the full-length BFV3026 clone produced viral structural and auxiliary proteins, typical cytopathic effects, and virus particles. These results demonstrate that the full-length BFV3026 clone is fully infectious and can be used in further BFV3026 research.
文摘We aim to provide an up-to-date summary of infantile hepatic hemangioma(IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver.Eligible peer-reviewed articles on hepatic infantile hemangiomas,published between 2000 and 2015,were reviewed for this study.IHH is the most common hepatic vascular tumor in children.Once a liver mass is identified in an infant,the differential diagnosis ranges from vascular malformations to benign and malignant tumors including mesenchymal hamartoma,hepatoblastoma,metastatic neuroblastoma,so careful physical examination,imaging studies,and,if indicated,tumor markers and biopsy,are of pivotal importance to ascertain the correct diagnosis.Despite the benign nature of IHHs,some of these lesions may demand medical and/or surgical intervention,especially for multiple and diffuse IHH.Complications can include hepatomegaly,hypothyroidism and cardiac failure.Therefore,a close follow-up is required until complete involution of the lesions.We propose an algorithm to guide the physicians towards the proper management of hepatic lesions.
文摘Recent advances in the management of lupus nephritis,together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy,have contributed to a favorable outcome in children and adolescents with systemic lupus erythematosus(SLE).Nevertheless,we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis.Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are reviewed.Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide(IVCY)are effective for preserving renal function in adult patients,CPA is a potent immunosuppressive agent that induces severe toxicity,including myelo-and gonadal toxicity,and increases the risk of secondary malignancy.Thus,treatment for controlling lupus nephritis activity,especially in children and adolescents,remains challenging.Cyclosporine A(Cs A)and tacrolimus(Tac)are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells,thereby inhibiting thetranscription of the early activation genes of interleukin(IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-α,IL-1βand IL-6.Therefore,both drugs,which we believe may be less cytotoxic,are attractive therapeutic options for young patients with lupus nephritis.Recently,a multidrug regimen of prednisolone(PDN),Tac,and mycophenolate mofetile(MMF)has been found effective and relatively safe in adult lupus nephritis.Since the mechanisms of action of MMF and Tac are probably complementary,multidrug therapy for lupus nephritis may be useful.We propose as an alternative to IVCY,a multidrug therapy with mizoribine,which acts very similarly to MMF,and Tac,which has a different mode of action,combined with PDN for pediatric-onset lupus nephritis.We also believe that a multidrug therapy including Cs A and Tac may be an attractive option for young patients with SLE and lupus
