Progress of lymphocyte activation gene 3 and programmed cell death protein 1 antibodies for cancer treatment: A review.

The application of immune checkpoint inhibitors has proven to be an effective treatment for cancer. Immune checkpoints such as programmed cell death protein 1/programmed cell death protein 1 ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T-cell immunoglobulin-3 (TIM-3), T-cell immunoglobulin and ITIM domain (TIGIT), and lymphocyte activation gene-3 (LAG-3) have received extensive attention, and the efficacy of antibodies or inhibitors against these checkpoints (either alone or in combination) has been evaluated in many tumors. This paper provides a brief overview of the PD-1 and LAG-3 checkpoints, and then shifts focus to the combined use of PD-1 and LAG-3 antibodies in both in vivo and in vitro experiments. In the in vitro experiments, we examined the correlation between the expression and activation of these inhibitors on T cells, and also assessed toxicity in animals in preparation for in vivo experiments. The effects of the combined use of PD-1 and LAG-3 antibodies were then summarized in animal models of melanoma, MC38 carcinoma, and other tumors. In clinical studies, the combined application of these antibodies was assessed in patients with melanoma, colorectal, breast, and renal cell cancers, as well as other solid tumors. In general, the combination of PD-1 and LAG-3 antibodies has shown promising results in both in vivo and in vitro studies.

Astragaloside IV inhibits Ang H-induced cell proliferation and collagen expression in cardiac fibroblasts by activating short-chain acyl-CoA dehydrogenase / 中国药理学通报

Aim To explore the effect of astragaloside IV (AS-IV) on cell proliferation and collagen expression in cardiac fibroblasts (CFs) of rats induced with angiotensin II (Ang II) and its mechanism. Methods CFs were pretreated with short-chain acyl-CoA dehydrogenase (SCAD) siRNA1186 for 12 h and then co-treated with Ang TJ and AS-IV for 36 h. The expressions of SCAD, α-SMA, collagen I and collagen III in CFs were detected by Western blot. mRNA expression levels of SCAD, a-SMA, collagen I and collagen III in CFs were detected by quantitative real-time PCR. The SCAD enzymatic activity, the content of ATP, hydroxyproline and free fatty acid were measured by detection kits. Results The expression of α-SMA, collagen I and collagen III were up-regulated (all P < 0. 01) in CFs induced by Ang II compared with the control cells, and the expression and enzymatic activity of SCAD significantly decreased (P < 0. 01, P< 0. 05). The content of ATP decreased (P < 0.01), and the content of hydroxyproline and free fatty acids increased (all P < 0.01). Compared with Ang II group, SCAD expression and enzymatic activity, and ATP content were significantly increased (all P < 0.01) in Ang II + AS-TV group, but the content of hydroxyproline and free fatty acids, and the expression of α-SMA, collagen I and collagen III significantly decreased (all P < 0.01). However, compared with the Ang II + NC group, there was no significant difference in all indices in the Ang II + SiRNA1186 + AS-TV group. The protective effect of AS-TV on Ang II -induced cell proliferation and collagen expression in CFs was eliminated by the interference of SCAD SiRNA1186. Conclusions AS-IV may inhibit Ang II-induced cell proliferation and collagen expression in CFs by activating SCAD.

Riboflavin inhibits heart failure in mice by activating SCAD / 中国药理学通报

Aim To explore the effeet of riboflavin on the establishment of pressure overload-induced heart failure model in mice by thoracic aortie constrietion (TAC ) and its preventive mechanism.Methods Eight-week-old SPF C57BL/6J mice were seleeted and divided into four groups; Sham group.Sham + ribofla¬vin group, TAC group and TAC + riboflavin group.A mouse heart failure model was constructed in the TAC group.The miee in the TAC + riboflavin group were given riboflavin by gavage one week before and eight weeks after the operation.The cardiac ultrasound inde¬xes, the changes of cardiac morphology and mitochon¬drial function indexes, the expression of apoptosis pro¬teins, ATP content, SCAD mRNA and protein expres¬sion, enzyme activity and flavin adenine dinucleotide (FAD) content in myocardial tissues were detected.Hie free fatty acid content in serum and myocardial tis¬sues were also detected.Results Compared with the sham group, the cardiac function indexes of the mice in the TAC group decreased, anrl typical heart failure occurred.Moreover, the expression of SCAD, enzyme activity, ATP and FAD content in the myocardium sig-nificantly decreased, and the free fatty acid content in myocardium and serum significantly increased.Com¬pared with the TAC group, after riboflavin treatment, the cardiac function of mice in TAC + Riboflavin group was significantly improved.In addition, ATP content, SCAD expression, enzyme activity and FAD content in myocardium all significantly increased, and free fatty acid content in myocardium and serum markedly de¬creased.Conclusions Riboflavin may improve myo-cardial energy metabolism by increasing FAD content and activating SCAD, thereby inhibiting pressure over¬load-induced heart failure in mice.

Changes of Serum Complement C1q in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To analyze the change of serum C1q in the course of multiple myeloma (MM) and its correlation with clinical characteristics.@*METHODS@#A total of 138 newly diagnosed MM patients in Zhongnan Hospital of Wuhan University from June 2016 to December 2019 were selected as research objects, during the same period 50 age-matched anemia patients, 50 lymphoma patients, 50 leukemia patients, and 50 myelodysplastic syndrome (MDS) patients were selected as control groups. All the patients met WHO disease classification, and were definitely diagnosed by pathology or bone marrow smear/biopsy. The changes of C1q between MM patients and control group, as well as in different therapeutic responses of MM patients before and after treatment were compared, also the difference of clinical characteristics among MM patients with different C1q level, so as to analyze risk factors which led to C1q decline.@*RESULTS@#The average value of C1q in MM patients was (128.18±51.24) mg/L, which was significantly lower than control group (P<0.01). The levels of white blood cell, platelet (PLT), hemoglobin (Hb), serum calcium, albumin, lactate dehydrogenase (LDH) in newly diagnosed high C1q group were significantly higher than those in low C1q group (P<0.05). Logistic analysis showed that the levels of PLT, Hb, albumin, and LDH in newly diagnosed high C1q group were higher than those in low C1q group (r=0.248, r=0.394, r=0.405, r=0.295). After treatment, the levels of C1q in MM patients with complete remission and very good partial remission were significantly higher than before treatment (P<0.05), while those with partial remission and stable disease also increased but not significantly (P>0.05).@*CONCLUSION@#The C1q level in MM patients is significantly lower than that in patients with other hematologic system diseases, and it increases with the remission of the disease after treatment.

Texture analysis of diffusion-weighted magnetic resonance imaging to identify atypically enhanced small hepatocellular carcinoma and dysplastic nodules under the background of cirrhosis / 中华肝脏病杂志

Objective@#To investigate the value of texture analysis based on diffusion-weighted magnetic resonance imaging (DWI) in the differential diagnosis of atypically enhanced small hepatocellular carcinoma (sHCC) and dysplastic nodules (DNs) in liver cirrhosis.@*Methods@#Data of 59 cases with atypical enhancement and solitary cirrhotic nodule (≤2 cm) confirmed by dynamic contrast enhanced MRI and surgical pathology specimen were analyzed retrospectively. Among them, 37 cases were of atypically enhanced sHCC and 22 cases of DNS. The DWI signal characteristics of the lesions were analyzed to measure the average apparent diffusion coefficient (ADC) value of the lesions, and the ADC ratio of the lesion to the liver parenchyma. MaZda software was used to manually draw the region of interest to extract the texture parameters of DWI lesions. The three sets (combination of Fisher coefficient, classification of error probability combined with average correlation coefficient and interactive information) were used to select the thirty optimal texture parameters. Raw data analysis (RDA), principal component analysis (PCA), linear discriminant analysis (LDA) and non-linear discriminant analysis (NDA) were performed for texture classification. The difference of ADC value and ADC ratio between sHCC and DNS group was compared by independent sample t-test, and χ2 test was used to compare the count data (or rate). ROC curve analysis was used to evaluate the diagnostic efficiency.@*Results@#The sensitivity, specificity and accuracy of DWI high-signal in the identification of atypically enhanced sHCC and DNs were 94.6% (35/37), 68.2% (15/22), and 84.7% (50/59), respectively. The ADC ratio of atypically enhanced sHCC was significantly lower than DNs, and the difference was statistically significant (t = 2.99, P = 0.002). The sensitivity, specificity, and accuracy for the diagnosis of atypically enhanced sHCC were 73.0% (27/37), 72.7% (16/22) and 72.9% (43/59), respectively. The sensitivity, specificity and accuracy of DWI texture analysis in diagnosing atypically enhanced sHCC were 94.6% (35/37), 95.5% (21/22) and 94.9% (56/59).The diagnostic efficiency of DWI texture analysis (AUC = 0.94) was significantly higher than DWI high-signal (AUC = 0.81) and ADC ratio (AUC = 0.72).@*Conclusion@#The texture analysis based on DWI can identify atypically enhanced sHCC and dysplastic nodules under the background of cirrhosis, and its efficacy is better than qualitative and quantitative DWI.

Effects of short-chain acyl-CoA dehydrogenase on hypertensive vascular remodeling / 中国病理生理杂志

AIM:To investigate the changes of short-chain acyl-CoA dehydrogenase(SCAD)in hypertensive vascular remodeling and to explore the relationship between SCAD and vascular remodeling in hypertension.METHODS:The spontaneously hypertensive rats(SHR;24 weeks old)and Wistar rats(24 weeks old)were used as experimental con-trol groups.The SHR and Wistar rats of 16 weeks old were trained by swimming as experimental groups.The systolic pres-sure was measured periodically.The thickness of vascular wall and the diameter of the vascular lumen were measured.The contents of ROS and ATP,the enzyme activity of SCAD, and the expression of SCAD at mRNA and protein levels in the aorta were determined.The free fatty acid in the serum and aorta was also measured.RESULTS:Compared with Wistar group,the diameter of vascular lumen decreased in SHR group.The thickness of vascular wall,the ratio of vascular wall and the diameter of vascular lumen,and the blood pressure in SHR group were increased significantly(P<0.05).Com-pared with SHR group,the diameter of vascular lumen increased in SHR +swim group.The thickness of vascular wall,the ratio of vascular wall and the diameter of vascular lumen,and the blood pressure in SHR +swim group were decreased sig-nificantly.Compared with control group, the expression of SCAD at mRNA and protein levels, the enzyme activity of SCAD,and the content of ATP were decreased in SHR group.However,the free fatty acid in the serum and aorta,and the content of ROS in the aorta were increased in SHR group.The expression of SCAD at mRNA and protein levels,the en-zyme activity of SCAD,the content of ATP were increased in Wistar +swim group and SHR +swim group.However, the free fatty acid in serum and aorta,and the content of ROS in the aorta were decreased in Wistar +swim group and SHR+swim group.CONCLUSION: Decrease in SCAD expression may be associated with hypertensive vascular remodeling. Swimming training can reverse hypertensive vascular remodeling by increasing the expression of SCAD in the aorta.

The complete mitochondrial genome sequence of Pterophyllum scalare (Cichliformes: Cichlidae).

Pterophyllum scalare belongs in the family Cichlidae of Cichliformes. This species and its congeners are characterized by a compressed and disc-shaped body with dorsal and anal spiny rays increasing in length from anterior to posterior part of the fin. In this study, we determine and describe the complete mitogenome sequence of Pterophyllum scalare for the first time, which is 16,494 bp in length, and contains 37 genes, including 13 protein-coding genes, 2 rRNAs, 22 tRNAs, 1 origin of replication on the light-strand (OL) and a putative control region. The overall base composition is 27.5% A, 26.8% T, 30.1% C and 15.6% G, with a slight AT bias (54.3%). All protein-coding genes share the start codon ATG, except for COI that begins with GTG. These results are expected to provide useful molecular data for phylogenetic studies of Cichlidae and Cichliformes. Maximum Likelihood (ML) tree and Bayesian analyses based on partitioned nucleotide sequences of 12 mitochondrial protein-coding genes were constructed and both yielded trees with identical topologies.

The complete mitochondrial genome sequence of Trichopodus leerii (Perciformes: Osphronemidae) and phylogenetic studies of Osphronemidae.

Trichopodus leerii has been given many popular names in the ornament market, such as pearl gourami, lace gourami and mosaic gourami, which causes confusion in species identification. This species belongs in the family Osphronemidae of Perciformes. This species and its congeners are characterized by a brownish-silver body, covered in a pearl-like pattern. In this study, we first determined and described the complete mitogenome sequence of T. leerii, which is 16,472 bp in length. The overall base composition is 29.2%, 27.3%, 28.0% and 15.5% for A, C, T and G, respectively, with a slight bias in the AT content (57.2%). All protein-coding genes share the start codon ATG and most of them have TAA or TAG as the stop codon, except ND4 and ND6 use an incomplete stop codon T. Maximum likelihood tree and Bayesian analyses based on partitioned nucleotide sequences of 12 mitochondrial protein-coding genes were constructed, and both yielded identical topologies. These results are expected to provide useful molecular data for species identification and further phylogenetic studies of Osphronemidae and Perciformes.

Expression and function of GSTA1 in lung cancer cells.

Glutathione S-transferase A1 (GSTA1) appears to be primarily involved in detoxification processes, but possible roles in lung cancer remain unclear. The objective of this study was to investigate the expression and function of GSTA1 in lung cancer cells. Real-time PCR and Western blotting were performed to assess expression in cancer cell lines and the normal lung cells, then verify the A549 cells line with stable overexpression. Localization of GSTA1 proteins was assessed by cytoimmunofluorescence. Three double-strand DNA oligoRNAs (SiRNAs) were synthesized prior to being transfected into A549 cells with Lipofectamine 2000, and then the most efficient SiRNA was selected. Expression of the GSTA1 gene in the transfected cells was determined by real-time PCR and Western blotting. The viability of the transfected cells were assessed by MTT. Results showed that the mRNA and protein expression of A549 cancer cells was higher than in MRC-5 normal cells. Cytoimmunofluorescence demonstrated GSTA1 localization in the cell cytoplasm and/or membranes. Transfection into A549 cells demonstrated that down-regulated expression could inhibit cell viability. Our data indicated that GSTA1 expression may be a target molecule in early diagnosis and treatment of lung cancer.

[Impact of biocontrol agent Bacillus subtilis on bacterial communities in tobacco rhizospheric soil].

The impact of inoculation with the biocontrol agent Bacillus subtilis on bacterial communities and bacterial diversity in rhizospheric soil of Nicotiana tabacum was assessed by constructing a 16S rRNA gene clone library and conducting amplified ribosomal DNA restriction analysis (ARDRA). The bacterial diversity was evaluated by coverage value (C), Shannon index (H), Pielou evenness index (E) and Margalef richness index (R). Phylogenetic analysis revealed that the inoculation significantly affected the composition of bacterial communities in tobacco rhizospheric soil. A total of twelve bacterial groups including Acidobacteria, Proteobacteria (including α-, ß-, δ-, γ-Proteobacteria) , Planctomycetes, Firmicutes, Nitrospirae, Gemmatimonadetes, Actinobacteria, Chloroflexi and Bacteroidetes were detected to be shared by inoculated soil and control soil. The community composition and proportions of different bacteria in the communities showed significant variations between the two samples. The dominant bacteria were Acidobacteria (27.1%) and Proteobacteria (26.5%) in control soil, while in the inoculated soil Proteobacteria (38.0%) and Acidobacteria (29.6%) were dominant. B. subtilis inoculation increased the numbers of γ-Proteobacteria and α-Proteobacteria but reduced the numbers of bacterial groups such as ß-Proteobacteria, Planctomycetes, Firmicutes. Diversity analysis showed that bacterial diversity was rich for both soil samples, and soil bacterial Shannon index and Margalef richness index were promoted after inoculation.

Comparison of ¹⁸F-FDG PET/CT and large-scale DWI for evaluation of non-Hodgkin lymphoma bone marrow infiltration / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the diagnostic value of ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and large-scale diffusion weighted imaging (DWI) for evaluation of non-Hodgkin lymphoma (NHL) bone marrow (BM) infiltration.</p><p><b>METHODS</b>A total of 79 patients with pathologically diagnosed NHL underwent ¹⁸F-FDG PET/CT, large scale DWI and BM pathological examination. BM examination as the "gold standard", the performance (the sensitivity, specificity, accuracy, positive and negative predictive value) of ¹⁸F-FDG PET/CT and large scale DWI for evaluation of BM infiltration was compared and the risk of BM infiltration of different subtypes and sources of NHL was analyzed.</p><p><b>RESULTS</b>25 of 79 cases were diagnosed as BM infiltration by pathological examination with 57 BM sites. Abnormal high BM metabolisms were identified in 22 cases with 56 BM sites by ¹⁸F-FDG PET/CT and 25 cases with 58 BM sites by large-scale DWI. The sensitivity, specificity, accuracy, positive and negative predictive value of ¹⁸F-FDG PET/CT were 80.0%, 96.3%, 91.1%, 90.9%, 91.2%, respectively. And they were 84.0%, 92.6%, 89.9%, 84.0%, and 92.6% by large-scale DWI, respectively. A receiver operating characteristic (ROC) analysis demonstrated that there was no statistical difference in ¹⁸F-FDG PET/CT and large-scale DWI (P>0.05). The area under ROC curve for ¹⁸F-FDG PET/CT and large-scale DWI were 0.911 and 0.883 respectively. The incidences of BM infiltration in aggressive NHL patients by ¹⁸F-FDG PET/CT (21/69, 30.4%) and large-scale DWI (23/69, 33.3%) were higher than those (PET/CT: 10.0%; large-scale DWI: 20.0%; P>0.05) in indolent NHL patients.</p><p><b>CONCLUSION</b>¹⁸F-FDG PET/CT and large-scale DWI had important clinical value in diagnosing BM infiltration of NHL. A combination of ¹⁸F-FDG PET/CT, large-scale DWI and pathological examination could improve the positive rate of BM infiltration in NHL.</p>

Human leukocyte antigen-C and killer cell immunoglobulin-like receptor gene polymorphisms among patients with syphilis in a Chinese Han population.

Syphilis is a sexually transmitted infection caused by the Treponema pallidum subspecies pallidum spirochete bacterium. The killer cell immunoglobulin-like receptors (KIR), interacting with human leukocyte antigens (HLA), regulate the activations of natural killer (NK) cells and certain T-cell subsets in response to microbe infection. The objective of this study was to explore whether KIR and HLA-C gene polymorphisms were associated with syphilis in a Chinese Han population. Polymerase chain reaction with sequence-specific primers (PCR-SSP) method was used to genotype KIR and HLA-C genes in 231 syphilis patients and 247 healthy controls. Framework genes KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 were present in all individuals. The frequencies of KIR2DS3 and KIR3DS1 were higher in syphilis patients than in healthy controls (p = 0.030 and p = 0.038, respectively), while the frequency of KIR2DS5 was higher in healthy controls than in syphilis patients (p = 0.015; OR = 0.575). The homozygote for HLA-C1 allele (HLA-C1C1) was more common in controls compared with syphilis patients (p = 0.030; OR = 0.667). The frequency of individuals with HLA-C1C1 and KIR2DL3 genotype was higher in control group relative to syphilis patient group (p = 0.018; OR = 0.647). These data indicated that KIR2DS3 and KIR3DS1 were more prevalent in syphilis patients than in controls, and that KIR2DS5, HLA-C1C1 and HLA-C1C1-KIR2DL3 were more prevalent in controls than in syphilis patients, respectively. These will require further investigation using functional studies.

IDH mutations predict longer survival and response to temozolomide in secondary glioblastoma.

Recent studies have shown that isocitrate dehydrogenase 1/2 (IDH1/2) mutations occur frequently in secondary glioblastoma. This study aimed to investigate their impact on temozolomide chemosensitivity and relationship with O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation in secondary glioblastoma. Searches for IDH1 and IDH2 mutations, 1p19q codeletion, MGMT promoter methylation, and p53 expression were carried out in a series of 86 secondary glioblastomas and correlated with progression-free survival and overall survival. Response to temozolomide was evaluated by progression-free survival, as well as by tumor size on successive MRI scans, then correlated with molecular alterations. IDH (IDH1 or IDH2) mutations were found in 58/79 patients (73.4%). IDH mutation, MGMT promoter methylation, and 1p19q codeletion were associated with prolonged progression-free survival in univariate (P < 0.001, P < 0.001, P = 0.003, respectively) and multivariate analysis (P < 0.001, P < 0.001, P = 0.035, respectively). IDH mutation (P = 0.001) and MGMT promoter methylation (P = 0.011) were correlated with a higher rate of objective response to temozolomide. Further analysis of response to temozolomide showed that patients with both IDH mutation and MGMT promoter methylation had the best response rate to temozolomide. IDH mutation appears to be a significant marker of positive chemosensitivity in secondary glioblastoma. Use of IDH status combined with MGMT promoter status as a stratification factor seems appropriate in future clinical trials involving temozolomide for the treatment of patients with secondary glioblastoma.

Tanshinone II-A attenuates cardiac fibrosis and modulates collagen metabolism in rats with renovascular hypertension.

The adaptive changes that develop in the pressure-overloaded left ventricular myocardium include cardiac hypertrophy and interstitial fibrosis. The objectives of the present study were to evaluate the effects of Tanshinone II-A, a bioactive diterpene quinone isolated from Danshen, on cardiac fibrosis and collagen metabolism in rats with renovascular hypertension. Male Sprague-Dawley rats were subjected to two-kidney two-clip (2K2C) or sham operation (sham) and treated with Valsartan (Val, 26.7 mg/kg/d), Tanshinone II-A (Tsn, 70, 35 mg/kg/d) or vehicle. Six weeks later, systolic blood pressure (BP), LV weight, collagen abundance, cardiac function parameters, hydroxyproline content and mRNA levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were evaluated. Both high-dose (Tsn-H, 70 mg/kg/d) and low-dose (Tsn-L, 35 mg/kg/d) of Tsn failed to attenuate 2K2C-induced BP elevation but significantly attenuated the attendant interstitial fibrosis. Val suppressed elevations of BP and left ventricular systolic pressure (LVSP) in 2K2C rats. Val and Tsn-H exerted comparable suppressive effects on the gene expression of MMP-9 and TIMP-1, while Val decreased the MMP-2 mRNA level without affecting the transcript levels of TIMP-2. Both Val and Tsn-H attenuated cardiac dysfunction, while Tsn-L showed slight improvement. These data demonstrate for the first time, that Tsn prevented cardiac fibrosis and improved cardiac function in a rat model of renovascular hypertensive independent of hypotensive effect. Tsn conferred its beneficial effects on the collagen metabolism probably through its regulation of transcript levels of the MMPs/TIMPs balance.

Reduced expression of GSTM2 and increased oxidative stress in spontaneously hypertensive rat.

Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The spontaneously hypertensive rat (SHR) is a well-characterized experimental model for essential hypertension. By comparative proteomics, we previously identified glutathione S-transferase, mu 2 (GSTM2), a protein involved in detoxification of reactive oxygen species, which had a significant reduction in left ventricles of 16-week-old SHR compared with WKY rats. In parallel, Western blotting and RT-PCR showed a similar reduction of GSTM2 in left ventricles and aortas of 4-, 8-, and 16-week-old SHR, which is before the onset of hypertension. This suggests that differential expression is not attributable to long-term changes in blood pressure. Meanwhile, the activities of GSTM2 were significantly decreased in different ages old SHR. Conversely, there was an enhanced generation of superoxide anion and activation of NADPH oxidase in SHR, which was accompanied by an increase in the protein expression of p47phox, a subunit of NADPH oxidase. These data suggest that it maybe a reduction in antioxidant defenses, evident by a reduced expression and activity of GSTM2, in the left ventricles and aortas of SHR that leads to increased levels of superoxide anion and activation of NADPH oxidase.

Proteomic analysis of hypertrophied myocardial protein patterns in renovascularly hypertensive and spontaneously hypertensive rats.

The cardiac protein profiles of spontaneously hypertensive and renovascularly hypertensive hypertrophy showed a significant alteration compared with normal hearts. Most proteins with significant modulations in their expressions belong to the category of metabolic and stress-related proteins. Among these proteins, glutathione-S-transferase mu2 and short-chain acyl-CoA dehydrogenase may be two candidate proteins associated with left ventricular hypertrophy in spontaneously hypertensive rats.

[Cyclosporin A inhibits the adhesion of neutrophil with ECV-304 induced by hypoxia/reoxygenation via ROS-Cyclophilin A-ERK1/2 pathway].

To investigate the inhibition of cyclosporin A (CsA) on neutrophil adhesion to human umbilical vein endothelial cells (HUVECs, ECV-304) induced by hypoxia/reoxygenation and further explore its mechanism, a 1 h hypoxia/4 h reoxygenation model was reproduced using ECV-304. The adhesion rate of neutrophils to ECV-304 was determined by measuring the activity of endogenous hexosaminidase. The expression of endothelial cell adhesion molecules of E-selectin and ICAM-1 was measured by flow cytometry. The expression of cyclophilin A (CyPA) and the activation of ERK1/2 was compared among experimental groups by Western blot. The content of reactive oxygen species (ROS) was measured by Fenton reaction. After being stimulated with 1 h hypoxia/4 h reoxygenation, ECV-304 showed an enhanced neutrophil adhensiveness in association with an increased surface expression of E-selectin and ICAM-1. In parallel, the content of ROS was also increased. These effects were significantly suppressed by the addition of CsA. Most importantly, the expression of CyPA was significantly increased following 1 h hypoxia/4 h reoxygenation, which was accompanied with an increased activation of ERK1/2. Treatment with CyPA inhibitor CsA and CyPA antisense oligonucleotides significantly inhibited the activation of ERK1/2 and decreased the adhesion of neutrophils to ECV-304. The specific ERK1/2 inhibitor PD98059 caused an inhibition of neutrophil adhesion to hypoxia/reoxygenation-stimulated ECV-304. Our data confirm that CsA inhibits neutrophil adhesion to hypoxia/reoxygenation stimulated ECV-304 by a mechanism involving inhibition of the signal transduction of ROS, CyPA and ERK1/2.

Cyclosporin A inhibits the adhesion of neutrophil with ECV-304 induced by hypoxia/reoxygenation via ROS-Cyclophilin A-ERK1/2 pathway / 生理学报

To investigate the inhibition of cyclosporin A (CsA) on neutrophil adhesion to human umbilical vein endothelial cells (HUVECs, ECV-304) induced by hypoxia/reoxygenation and further explore its mechanism, a 1 h hypoxia/4 h reoxygenation model was reproduced using ECV-304. The adhesion rate of neutrophils to ECV-304 was determined by measuring the activity of endogenous hexosaminidase. The expression of endothelial cell adhesion molecules of E-selectin and ICAM-1 was measured by flow cytometry. The expression of cyclophilin A (CyPA) and the activation of ERK1/2 was compared among experimental groups by Western blot. The content of reactive oxygen species (ROS) was measured by Fenton reaction. After being stimulated with 1 h hypoxia/4 h reoxygenation, ECV-304 showed an enhanced neutrophil adhensiveness in association with an increased surface expression of E-selectin and ICAM-1. In parallel, the content of ROS was also increased. These effects were significantly suppressed by the addition of CsA. Most importantly, the expression of CyPA was significantly increased following 1 h hypoxia/4 h reoxygenation, which was accompanied with an increased activation of ERK1/2. Treatment with CyPA inhibitor CsA and CyPA antisense oligonucleotides significantly inhibited the activation of ERK1/2 and decreased the adhesion of neutrophils to ECV-304. The specific ERK1/2 inhibitor PD98059 caused an inhibition of neutrophil adhesion to hypoxia/reoxygenation-stimulated ECV-304. Our data confirm that CsA inhibits neutrophil adhesion to hypoxia/reoxygenation stimulated ECV-304 by a mechanism involving inhibition of the signal transduction of ROS, CyPA and ERK1/2.

[Effects of hypoxic preconditioning on the adhesion of neutrophils to vascular endothelial cells induced by hypoxia/reoxygenation].

OBJECTIVE: To investigate whether hypoxic preconditioning (HPC) can inhibit neutrophils (PMN) adhesion to vascular endothelial cell (VEC). METHODS: The adhesion of PMN to VEC was measured by endogenous enzyme hexosaminidase. The effect of HPC on the expression of endothelial cell (EC) adhesion molecules was determined with flow cytometry. RESULTS: After stimulated with 1 hour of hypoxia (H) followed by 4 hours of reoxygenation (R), VEC showed an enhanced PMN adhensivity in association with an increased surface expression of E-selectin and intracellular adhesion molecules-1 (ICAM-1). HPC suppressed the expression of E-selectin and ICAM-1 with a subsequent inhibition of PMN adhesion to hypoxia/reoxygenation (H/R) stimulated VEC. CONCLUSION: HPC inhibits PMN adhesion to VEC through regulating the expression of EC adhesion molecules.