Corrigendum: Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

[This corrects the article DOI: 10.3389/fpsyt.2024.1354999.].

Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

Life extension factor klotho regulates behavioral responses to stress via modulation of GluN2B function in the nucleus accumbens.

Klotho is a life extension factor that has the ability to regulate the function of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs), whose dysfunction in the nucleus accumbens (NAc) underlies critical aspects of the pathophysiology of major depression. Here, we study the functional relevance of klotho in the pathogenesis of depression. A chronic social defeat stress paradigm, in which mice are categorized as either susceptible or unsusceptible based on their performance in a social interaction test, was used in this study. We found that the expression of klotho was largely decreased in the NAc of susceptible mice compared to control or unsusceptible mice. Genetic knockdown of klotho in the NAc induced behavioral alterations relevant to depression in naive mice, while overexpression of klotho produced an antidepressive effect in normal mice and ameliorated the behavioral responses to stress in susceptible mice. Molecularly, knockdown of klotho in the NAc resulted in selective decreases in total and synaptic GluN2B expression that were identical to those in susceptible mice. Elevation of klotho in the NAc reversed the reductions in GluN2B expressions and altered synaptic transmission and spine density in the NAc of susceptible mice. Furthermore, blockade of GluN2B with a specific antagonist abolished the beneficial effects of klotho elevation in susceptible mice. Collectively, we demonstrated that klotho in the NAc modulates behavioral responses to stress by regulating the function of GluN2B-containing NMDARs. These results reveal a novel role for klotho in the pathogenesis of depression, providing new insights into the molecular basis of major depression.

CircRPPH1 promotes cell proliferation, migration and invasion of non-small cell lung cancer via the PI3K/AKT and JAK2/STAT3 signalling axes.

Non-small cell lung cancer (NSCLC) has markedly increased morbidity and mortality rates worldwide. Circular RNAs were shown to regulate NSCLC progression. But the underlying pathways of the circRPPH1-mediated regulation of NSCLC still need further exploration. We evaluated circRPPH1 levels in NSCLC tissues and cell lines via qRT-PCR. Moreover, using ectopic plasmid incorporation and siRNA assays, we analysed the circRPPH1-mediated regulation of cell proliferation (CP), cell migration (CM) and cell invasion (CI) in NSCLC cell lines (H1975 and A549 cells), using CCK-8, colony forming, scratch wound and transwell assays, respectively. CircRPPH1 levels were remarkably high in the NSCLC tissues and cell lines. The transfection experiments showed that circRPPH1 overexpression was able to promote CP, CM and CI of NSCLC cells, while CP, CM and CI were significantly restrained by the knockdown of circRPPH1. We also displayed that circRPPH1 knockdown suppressed the cell progression via inactivating the PI3K/AKT and JAK2/STAT3 signalling axes. Subsequently, in vivo experiment in nude mice was demonstrated that the inhibition of circRPPH1 could reduce the tumour growth of NSCLC. circRPPH1 may accelerate the growth and metastasis of NSCLC, in culture conditions and in animal models, by stimulating the PI3K/AKT and JAK2/STAT3 signalling axes, thus promoting the development of NSCLC.

Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia.

Cognitive deficits are the core feature of schizophrenia and effective treatment strategies are still missing. Previous studies have reported that fisetin promotes long-term potentiation (LTP) and cognitive function in normal rodents and other model animals of neurological diseases. The aim of this study was to assess the effect of fisetin on synaptic plasticity and cognitive deficits caused by a brief disruption of N-methyl-D-aspartate receptors (NMDARs) with dizocilpine (MK-801) during early development in rats. The cognitive performance was examined by the Morris water maze task and a fear conditioning test. Hippocampal synaptic plasticity was investigated by field potential recording. The expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) and cognition-related proteins was measured by western blotting. We found that intraperitoneal administration of fisetin rescued hippocampus-dependent spatial and contextual fear memory in MK-801 rats. In parallel with these behavioral results, fisetin treatment in MK-801 rats reversed the impairment of hippocampal LTP. At the molecular level, fisetin treatment selectively increased the phosphorylation and surface expression of AMPA receptor subunit 1 (GluA1) in MK-801-treated rats. Moreover, fisetin restored the phosphorylation levels of calcium-calmodulin-dependent kinaseII (CaMKII), cAMP response element-binding protein (CREB), and the extracellular signal-regulated kinase (ERK1/2) in MK-801-treated rats. Collectively, our findings demonstrate that fisetin treatment can reverse the deficits of hippocampal synaptic plasticity and memory in a male rat model of schizophrenia by restoring the phosphorylation and surface expression of AMPAR GluA1 subunit, suggesting fisetin as a promising therapeutic candidate for schizophrenia-associated cognitive deficits.

Decreased Plasma Levels of Growth Differentiation Factor 11 in Patients With Schizophrenia: Correlation With Psychopathology and Cognition.

Schizophrenia is linked with abnormal neurodevelopment, on which growth differentiation factor 11 (GDF-11) has a great impact. However, a direct evidence linking GDF-11 to the pathophysiology of schizophrenia is still lacking. The current study aimed to investigate the relationship between plasma GDF-11 levels and both psychopathological symptoms and cognitive function in schizophrenia. Eighty-seven schizophrenia patients and 76 healthy controls were enrolled in the present study. The symptomatology of schizophrenia was evaluated using the Positive and Negative Syndrome Scale (PANSS). Cognitive function was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) including twelve neurocognitive tests in five aspects of cognitive function. Plasma GDF-11 levels were determined by enzyme-linked immunosorbent assay (ELISA). We found that plasma levels of GDF-11 were significantly lower in schizophrenia patients relative to healthy controls. Correlation analysis showed significant negative correlations between the GDF-11 levels and the PANSS total score, the positive symptoms score, the negative symptoms score or the general score. Additionally, positive associations were observed between plasma GDF-11 levels and the visuospatial/constructional, attention, immediate memory, or delayed memory in patients. Partial correlation analysis showed that these correlations were still significant after adjusting for age, gender, education years, body mass index, duration of illness, and age of onset except for the visuospatial/constructional and attention index. Multiple regression analysis revealed that GDF-11 was an independent contributor to the immediate memory, delayed memory and RBANS total score in patients. Collectively, the correlations between plasma GDF-11 and psychopathological and cognitive symptoms suggest that abnormal GDF-11 signaling might contribute to schizophrenic psychopathology and cognitive impairments and GDF-11 could be a potential and promising biomarker for schizophrenia.

Erratum to: Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics.

The article "Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics", written by Xue-lin CHAO, Shu-zhen JIANG, Jian-wen XIONG, Jin-qiong ZHAN, Bo WEI, Chun-nuan CHEN, Yuan-jian YANG was originally published electronically on the publisher's internet portal on June 2020 without open access. With the author(s)' decision to opt for Open Choice, the copyright of the article is changed to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics.

Accumulating evidence suggests that a disruption of early brain development, in which insulin-like growth factor-2 (IGF-2) has a crucial role, may underlie the pathophysiology of schizophrenia. Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia. Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients. Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and serum IGF-2 levels were determined using ELISA. We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline (P<0.05). After 2 months of atypical antipsychotic treatment, a significant improvement in each PANSS subscore and total score was observed in patients (all P<0.01), and the serum IGF-2 levels of patients were significantly increased compared with those at baseline (203.13±64.62 vs. 426.99±124.26 ng/mL; t =-5.044, P<0.001). Correlation analysis revealed that the changes of serum IGF-2 levels in patients were significantly correlated with the improvements of negative symptoms (r=-0.522, P=0.006). Collectively, our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics, suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.

Increased Plasma Level of Longevity Protein Klotho as a Potential Indicator of Cognitive Function Preservation in Patients With Schizophrenia.

Cognitive impairments are a core feature of schizophrenia. Klotho is an anti-aging protein with demonstrated cognitive-enhancing effects on the brain. The purpose of this study was to investigate the differences in levels of plasma klotho between patients with schizophrenia and healthy controls, as well as the relationship between klotho level and cognitive function in patients. Forty patients with schizophrenia and 40 gender- and age-matched healthy individuals were recruited. Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology of patients. A neuropsychological battery was performed to evaluate the cognitive function of participants. Plasma klotho was measured using enzyme-linked immunosorbent assay. We show that patients with schizophrenia performed worse in the neurocognitive tests than the healthy controls. The levels of plasma klotho were significantly higher in schizophrenia patients than in healthy controls (p < 0.001). In patients, plasma klotho levels were positively correlated with cognitive function with regard to attention (p = 0.010), working memory (p < 0.001), verbal memory (p = 0.044), executive function (p < 0.001), and composite cognitive score (p < 0.001). Stepwise linear regression analysis shows that executive function had the highest correlation with plasma klotho levels (ß = 0.896, t = 8.290, p < 0.001). Collectively, these results indicate that anti-aging protein klotho may be implicated in the pathogenesis of schizophrenia, and increased klotho may act as a compensatory factor for the preservation of cognitive function in schizophrenia. Further studies are needed to investigate the dynamic changes of klotho and the mechanisms by which klotho modulates cognition in schizophrenia.

Altered insulin-like growth factor-2 signaling is associated with psychopathology and cognitive deficits in patients with schizophrenia.

BACKGROUND: Schizophrenia is linked with abnormal brain neurodevelopment, on which IGF-2 (insulin-like growth factor-2) has a great impact. The purpose of this study was to assess the levels of serum IGF-2 and its binding proteins IGFBP-3 and IGFBP-7 in schizophrenia patients and the associations of these proteins with schizophrenia psychopathology and cognitive deficits. METHODS: Thirty-two schizophrenia patients and 30 healthy controls were recruited. The PANSS and a neurocognitive test battery were used to assess schizophrenic symptomatology and cognition, respectively. Serum IGF-2, IGFBP-3 and IGFBP-7 levels were determined using ELISA. RESULTS: The schizophrenia patients had a much lower content of serum IGF-2, IGFBP-3 and IGFBP-7 than controls. For the patients, IGF-2 levels were negatively correlated with the PANSS negative scores and positively associated with working memory, attention, and executive function. The correlations between IGF-2 and the PANSS negative scores, working memory or executive function were still significant after controlling for age, sex, education level, BMI, illness history and age of onset. No significant associations of IGFBP-3 or IGFBP-7 with the PANSS scores and cognitive function were observed in the patients. CONCLUSIONS: Our study demonstrates that serum IGF-2 was significantly correlated with negative and cognitive symptoms in patients with schizophrenia, suggesting that altered IGF-2 signaling may be implicated in the psychopathology and cognitive deficits in schizophrenia.

The association between serum insulin-like growth factor 1 and cognitive impairments in patients with schizophrenia.

Accumulating evidence has shown that insulin-like growth factors (IGFs) are implicated in schizophrenia. Altered serum levels of IGF-1 have been found in schizophrenia patients and are associated with psychopathological symptoms. However, whether there is a relationship between IGF-1 and cognitive impairment in schizophrenia remains unknown. Thirty schizophrenia patients and 26 healthy controls were recruited for this study. The Positive and Negative Syndrome Scale was adopted to assess schizophrenic symptoms, and a battery of neuropsychological tests was employed to evaluate cognitive function. Serum IGF-1 content was determined by enzyme-linked immunosorbent assay (ELISA). We found that patients with schizophrenia performed more poorly than healthy controls in most cognitive tasks, excluding visual memory. The serum IGF-1 concentrations in schizophrenia patients were much lower than those in controls. Correlation analyses revealed that the levels of serum IGF-1 were positively correlated with executive function and attention scores in patients. Furthermore, IGF-1 was an independent contributor to deficits in executive function and attention among schizophrenia patients. Collectively, serum IGF-1 levels were significantly correlated with cognitive performance in schizophrenia patients, indicating that decreased IGF-1 levels might contribute to the pathophysiology of schizophrenia-associated cognitive impairments. The regulation of IGF-1 signaling might be a potential treatment strategy for cognitive impairments in schizophrenia.

Rectification of chiral active particles driven by transversal temperature difference.

Rectification of chiral active particles driven by transversal temperature difference is investigated in a two-dimensional periodic channel. Chiral active particles can be rectified by transversal temperature difference. Transport behaviors are qualitatively different for different wall boundary conditions. For the sliding boundary condition, the direction of transport completely depends on the chirality of particles. The average velocity is a peaked function of angular velocity or temperature difference. The average velocity increases linearly with the self-propulsion speed, while it decreases monotonically with the increase in the packing fraction. For randomized boundary condition, the transport behaviors become complex. When self-propulsion speed is small, in contrast with the sliding boundary condition, particles move in the opposite direction. However, for large self-propulsion speed, current reversals can occur by continuously changing the system parameters (angular velocity, temperature difference, packing fraction, and width of the channel).

Transport of particles driven by the traveling obstacle arrays.

Transport of three types of particles (passive particles, active particles without polar interaction, and active particles with polar interaction) is numerically investigated in the presence of traveling obstacle arrays. The transport behaviors are different for different types of particles. For passive particles, there exists an optimal traveling speed (or the translational diffusion) at which the average velocity of particles takes its maximum value. For active particles without polar interaction, the average velocity of particles is a peaked function of the obstacle traveling speed. The average velocity decreases monotonically with increase of the rotational diffusion for large driving speed, while it is a peaked function of the rotational diffusion for small driving speed. For active particles with polar interaction, interestingly, within particular parameter regimes, active particles can move in the opposite direction to the obstacles. The average velocity of particles can change its direction by changing the system parameters (the obstacles driving speed, the polar interaction strength, and the rotational diffusion).

Decreased plasma levels of gasotransmitter hydrogen sulfide in patients with schizophrenia: correlation with psychopathology and cognition.

OBJECTIVE: Aberrant N-methyl-D-aspartate receptor (NMDAR) function has been implicated in the pathophysiology of schizophrenia. Hydrogen sulfide (H2S) is an endogenous gasotransmitter that regulates NMDAR function. The current study investigated the relationship between plasma H2S levels and both psychopathological and cognitive symptoms in schizophrenia. MATERIALS AND METHODS: Forty-one patients with schizophrenia and 40 healthy control subjects were recruited in present study. Schizophrenic symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive function was evaluated with a neuropsychological battery including seven neurocognitive tests. Plasma H2S levels were measured by reversed-phase high-performance liquid chromatography (RP-HPLC). RESULTS: Patients with schizophrenia performed worse in all of the cognitive tests than the healthy controls except for the visual memory. Plasma H2S levels were significantly lower in patients with schizophrenia relative to healthy control subjects (F = 3.821, p = 0.007). Correlation analysis revealed a significant negative correlation between the H2S levels and the PANSS general scores (r = - 0.413, p = 0.007). Additionally, a positive association was observed between plasma H2S levels and working memory (r = 0.416, p = 0.007), visual memory (r = 0.363, p = 0.020), or executive function (r = 0.344, p = 0.028) in patients. Partial correlation analysis showed that the correlations between the H2S levels and the PANSS general scores, working memory, visual memory, or executive function were still significant when controlling for age, gender, years of education, BMI, duration of illness, and age of onset. CONCLUSION: The significant relations observed in the current study between H2S and the general psychopathological as well as cognitive symptoms suggest that decreased H2S is involved in the psychopathology and cognitive deficits of schizophrenia, and it might be a promising peripheral biomarker of schizophrenia.

Treatment Responses of Cognitive Function and Plasma Asymmetric Dimethylarginine to Atypical Antipsychotic in Patients With Schizophrenia.

Cognitive deficits represent a core feature of schizophrenia. Previous studies have demonstrated that plasma asymmetric dimethylarginine (ADMA) was increased in patients with schizophrenia and correlated with cognitive impairments. Atypical antipsychotics can produce cognitive benefits in schizophrenia patients. In this study, we conducted a prospective observation trial to explore whether plasma ADMA may serve as an indicator for evaluating cognitive improvements induced by atypical antipsychotics in patients with schizophrenia. A total of 41 schizophrenia patients with acute exacerbation were enrolled and 29 patients completed this study. These recruited patients were drug-naive or had no exposure to antipsychotics for at least 3 months. Thirty healthy individuals were recruited as a control group. Positive and Negative Syndrome Scale (PANSS) and a neuropsychological battery were used to evaluate schizophrenic symptoms and cognitive function, respectively. Plasma ADMA was measured by high-performance liquid chromatography (HPLC). We found that schizophrenia patients with acute exacerbation had significantly poorer cognitive performances and higher plasma ADMA levels than control individuals (p < 0.05). After 2 months of atypical antipsychotic treatment, patients showed significant improvements in processing speed, working memory, attention, and executive function (all p < 0.01). Plasma ADMA levels in patients after treatment were significantly decreased compared to baseline (2.42 ± 0.84 vs. 1.55 ± 0.34 µmol/L; t = 6.491, p < 0.001). Correlation analysis reveals that there is a significant correlation of the decrease in ADMA with improvements in working memory (r = -0.413, p = 0.026) and attention (r = -0.417, p = 0.025). Collectively, our results suggest that atypical antipsychotics improve cognitive function in schizophrenia patients with acute exacerbation, in parallel with decreased plasma ADMA levels. Plasma ADMA levels may be an indicator of cognitive recovery in schizophrenia.

Increased plasma asymmetric dimethylarginine is associated with cognitive deficits in patients with schizophrenia.

Cognitive deficits are a core feature of schizophrenia. Previous studies have shown that plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, was increased in patients with schizophrenia. This study aimed to investigate the association of ADMA with cognitive deficits in schizophrenia. Forty-seven patients with schizophrenia and 45 healthy control subjects were recruited in present study. Cognitive function was assessed with a neuropsychological battery including 7 neurocognitive tests. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale and plasma ADMA concentration was measured by HPLC. We found that patients with schizophrenia exhibited poorer performances in nearly all of the cognitive tests except for the visual memory index compared with healthy controls. Plasma ADMA levels were significantly increased in patients with schizophrenia when compared to normal controls, and the mean ADMA concentration in patients with multiple episode schizophrenia was much higher than that of patients with first episode schizophrenia. For the patients, ADMA was negatively associated with attention, working memory and executive function in schizophrenia. These results suggest that ADMA may be involved in the pathophysiology of schizophrenia-associated cognitive impairments, and plasma ADMA could be a peripheral biomarker for evaluation of cognitive function in schizophrenia.

Brownian transport of finite size particles in a periodic channel coexisting with an energetic potential.

Transport of particles with different sizes moving in a two-dimensional periodic channel is studied in the presence of an unbiased external force and a periodic energetic potential. While particles are going through entropic barrier resulting from the geometric restraints, the transport is also influenced by the energetic potential. For the case of an unbiased external force, the competition between the energetic potential and entropic barrier leads to different transport direction of particles, which sensitively depends on the particles radius. Particles move to the left when smaller than a critical radius and larger than another critical radius, whereas particles move to the right in the range of two critical radii. Therefore, the results we have presented can contribute further to the invention of machines for particle separation.

[A study on expression of Wnt signal pathway gene in familial aggregated hypertension].

OBJECTIVE: To determine the role of gene expression of Wnt signal pathway in the pathogenesis of familial aggregated hypertension. METHODS: The patients having directly related family members for more than three generations suffering from hypertension were enlisted in the hypertension group, and healthy individuals served as control group. The real-time polymerase chain reaction (PCR) gene array was used to detect the expression of functional classification genes of Wnt signal pathway in peripheral blood, with standard value deviated>2.0 from hypertension group/control group as differential genes. RESULTS: When hypertension group was compared with the control group, there were 6 differentially expressed genes, with 5 genes up-regulated, including Bcl-9, microphthalmia associated transcription factor (Mitf), secreted frizzled-related protein-1 (Sfrp-1), Wnt inhibiting factor-1 (Wif-1) and ribosomal protein-l13a (Rp-l13a). There was 1 gene down-regulated, i.e. dickkopf homolog-3 (Dkk-3). CONCLUSION: The result of this study suggested that the Wnt signal pathway may be related to the occurrence and development of the familial aggregated hypertension.

[Study on cardiovascular diseases marker gene expression profile of familial aggregation hypertension].

OBJECTIVE: To explore the cardiovascular diseases marker gene expression profile of the familial aggregation hypertension patients,and to screen differentially expressed genes. METHODS: The patients who had directly related family members for more than three generations suffering from hypertension were selected as experiment group, and healthy individuals as control group. Oligo GEArray gene chip technique was used to detect the expression of cardiovascular diseases marker gene in peripheral blood. The ratio of positive/negative standard value >2.0, or ≤0.5 and >0 was identified as differential gene. RESULTS: Compared with control group, there were 10 up-regulated differential genes in experiment group, composing genes involved in lipid metabolism, immune response-related molecules, cell adhesion molecules, extracellular molecules and coagulation, including apolipoprotein E (ApoE), epithelial V-like antigen-1 (EVA-1), interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), IL-8, integrin-ß1 (ITGB-1), matrix metalloproteinase-9 (MMP-9), nuclear factor-ΚB (NF-ΚB), platelet endothelial cell adhesion molecule-1 (PECAM-1), selectin-P (SEL-P). There were 3 down-regulated genes, including coagulation factors-III (F-III), lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), and serine protease inhibitor-1 (SERPINE-1). CONCLUSION: This study suggested that familial aggregation hypertension related to a variety of gene markers of cardiovascular disease, especially elements concerning coagulation and extracellular protease inhibitor-related genes.

[Mechanism of inhibition of apoptosis of human umbilical vein endothelial cells induced by oxidized-low density lipoprotein by erythropoietin].

OBJECTIVE: To explore the protective effect of erythropoietin (EPO) against oxidized-low density lipoprotein (ox-LDL)-induced apoptosis in human umbilical vein endothelial cells (HUVECs) in an ox-LDL induced apoptosis model. METHODS: Third-sixth passage of cultured HUVECs were used, and they were divided into two groups. The cells were pretreated with different concentrations (6.25, 50, 100 kU/L) of recombinant human erythropoietin (rhEPO) for 24 hours, then they were exposed to ox-LDL (100 mg/L) for 48 hours; another group of cells were pretreated with antisense to 0.5 micromol/L LOX-1 mRNA or 0.5 micromol/L sense for 24 hours, and then HUVECs were exposed to ox-LDL (100 mg/L) for 12 hours. Apoptosis was assessed by the apoptosis ratio, cell viability, and Bcl-2/Bax ratio. RESULTS: As compared to untreated controls, pretreatment with rhEPO led to increased cell survival of HUVECs and decreased cell apoptosis in a dose-dependent manner (all P<0.05). Consistently, the Bcl-2/Bax ratios were also increased in a similar fashion. The ratio of apoptosis protein Bcl-2/Bax was increased in the antisense LOX-1 mRNA group than that of ox-LDL group (P<0.05), but the one in the sense LOX-1 mRNA group was not significantly different from that of ox-LDL group. CONCLUSION: The ox-LDL can induce apoptosis in HUVECs by regulating LOX-1 mRNA, and rhEPO can increase Bcl-2/Bax ratio and inhibit ox-LDL-induced apoptosis of HUVECs.