Comparison of Long-Term Clinical Outcomes and Costs Between Transesophageal Echocardiography-Guided and X-ray-Guided Percutaneous Atrial Septal Defect Closure in Children.

This study aimed to compare the long-term clinical outcomes and costs between using either transesophageal echocardiography (TEE) or X-ray fluoroscopy for Percutaneous atrial septal defect (ASD) closure in children. An analysis was conducted on clinical data from children undergoing TEE-guided (n = 168) and X-ray-guided (n = 139) percutaneous ASD closure. Demographic characteristics, technical indices, acute complications, follow-up outcomes, and costs were compared between the groups. The results are that TEE-guided closure demonstrated shorter surgical times (20.3 ± 7.6 min vs. 32.8 ± 7.9 min, P < 0.001) and lower procedural costs ($3093.3 ± 451.5 vs. $3589.1 ± 219.4, P < 0.001) compared to X-ray guidance. Initial successful closure rates were similar between the groups (TEE: 98.2%, XR: 97.1%, P = 0.691). TEE guidance also resulted in fewer acute complications and reduced radiation exposure. TEE-guided percutaneous ASD closure offers advantages in terms of shorter surgical times, lower procedural costs, and reduced radiation exposure compared to X-ray guidance. These findings support the preference for TEE guidance in pediatric ASD closure procedures, with potential implications for improving patient outcomes and reducing healthcare costs.

Uni-Port Total Thoracoscopic Surgery Versus Median Sternotomy for Redo Tricuspid Valve Replacement: A Retrospective Study.

BACKGROUND: This study compared the perioperative and follow-up period data of patients who underwent redo tricuspid valve replacements performed via thoracoscopic surgery or median sternotomy. The purpose was to evaluate the feasibility, safety, and surgical outcomes of redo tricuspid valve replacement via uni-port thoracoscopic surgery. METHODS: Forty-nine patients with severe tricuspid valve regurgitation after left-side valve replacement underwent redo tricuspid valve replacements in our hospital from April 2012 to September 2019. Twenty-six patients underwent uni-port total thoracoscopy surgery, whereas 23 patients had the surgery performed via median sternotomy. We collected perioperative and 3- to 36-month postoperative data. RESULTS: No deaths occurred in the intraoperative period. Time of cardiopulmonary bypass in the study group significantly was longer than that in the control group (P < .05), but the operative times in the study and control groups were not significantly different. Thoracic drainage, length of ICU stay, postoperative hospital stay, and complication rates in the study group were significantly different from those in the control group (P < .05). Throughout the follow-up period, uni-port total thoracoscopic TVR was not inferior to traditional surgery with respect to cardiac function and recurrence of tricuspid valve regurgitation. CONCLUSIONS: Uni-port total thoracoscopic tricuspid valve replacement is safe,  feasible and effective, and that can be considered as a primary treatment strategy for patients with severe TR after previous left-sided valve procedure.

[Impairment of the hypothalamus and striatum of rats following lead exposure].

OBJECTIVE: To investigate the impairment of lead exposure on rat hypothalamus and striatum. METHODS: Forty-five healthy SPF male SD rats were randomly divided into three groups, control group( double distilled water), low( 60 mg/kg BW) and high dose( 120 mg/kg BW) groups. The rats were treated with lead acelate water solution in lead exposure group by gavage for 9 weeks. Open-field test was used to detect behavioral changes of the rats. The lead content of hypothalamus and striatum was determined by inductively coupled plasma mass spectrometry( ICP-MS). The mRNA expressions of toll-like receptor 4( TLR4), nuclear transcription factor kappa B( NF-κB), tumor necrosis factors alpha( TNF-α), interleukin-1( IL-1ß) and 8-oxoguanine DNA glycosylase( OGG1) were measured by real-time PCR. Enzyme linked immunosorbent assay( ELISA) was applied to detect the protein content of TLR4, NF-κB, TNF-α, IL-1ß and 8-hydroxy-2-deoxyguanosine( 8-OHd G). RESULTS: There were no significant differences in terms of body weight among three groups of rats. Compared with the control group, total movement distance, the total number of lattice and the distance of the central region in low and high lead exposure group were significantly decreased( P < 0. 05). The lead contents in hypothalamus and striatum of rats of low and high lead exposure group were( 60. 10 ± 6. 71), ( 71. 20 ± 11. 24), ( 44. 07 ± 9. 63)and( 66. 67 ± 8. 78) µg/g, respectively, higher than those in the control group(( 33. 77± 8. 19), ( 25. 75 ± 6. 33) µg/g)( P < 0. 05). While compared with the control group, the mRNA expression of NF-κB and OGG1 of the low and high lead exposure group were( 3. 47 ± 0. 15), ( 1. 43 ± 0. 16) and( 0. 67 ± 0. 13), ( 0. 57 ± 0. 19) folds in hypothalamus, there were marked differences in the mRNA expression of TLR4 and NF-κB between low and high lead group. The NF-κB, TNF-α, IL-1ß protein contents in hypothalamus of the low lead exposure group were( 5. 85 ± 1. 10), ( 56. 15 ± 6. 96) and( 1. 18 ± 0. 20) ng/g, respectively higher than those in control group(( 3. 03 ± 0. 71), ( 49. 25 ± 7. 21) and( 0. 86 ± 0. 11) ng/g)( P < 0. 05). The TLR4, NF-κB, TNF-α, IL-1ß protein contents in hypothalamus of the high lead exposure group were( 0. 67 ± 0. 12), ( 4. 74 ± 0. 68), ( 69. 73 ± 9. 61) and( 1. 43 ± 0. 29) ng/g, respectively, higher than those in control group. There were marked differences in the protein contents of TLR4 and TNF-α significant between low and high lead group in hypothalamus. The mRNA expression of TLR4, NF-κB, IL-1ß in the striatum of rats in the high lead exposure group were significantly higher than those in control group( P < 0. 05). The TLR4, NF-κB, TNF-α, IL-1ß, 8-OHd G protein contents of the high lead exposure group were( 0. 33 ±0. 02) ng/g, ( 4. 66 ± 0. 51), ( 82. 63 ± 7. 99), ( 1. 92 ± 0. 35) and( 1. 21 ± 0. 14) ng/g, respectively higher than those in control group( P < 0. 05), NF-κB protein content of the high lead exposure group was higher than that in low lead exposure group( P < 0. 05). CONCLUSION: Lead exposure does result in the impairment of hypothalamus and striatum, indicating that inflammation and oxidative damage might be involved in this process.

[Effects of lead exposure on copper and copper transporters in choroid plexus of rats].

OBJECTIVE: To investigate the effects of lead exposure on the copper concentration in the brain and serum and the expression of copper transporters in the choroid plexus among rats. METHODS: Sixty specific pathogen-free Sprague-Dawley rats were randomly divided into a control group and three lead-exposed groups, with 8 mice in each group. The lead-exposed groups were orally administrated with 500 (low-dose group)), 1 000 (middle-dose group), and 2 000 mg/L (high-dose group) lead acetate in drinking water for eight weeks. And the rats in control group were given 2 000 mg/L sodium acetate in drinking water. The content of lead and copper in the serum, hippocampus, cortex, choroid plexus, bones, and cerebrospinal fluid (CSF) was determined by inductively coupled plasma-mass spectrometry (ICP-MS). Confocal and real-time PCR methods were applied to measure the expression of copper transporters including copper transporter 1 (Ctr1), antioxidant protein 1 (ATX1), and Cu ATPase (ATP7A). RESULTS: Compared with the control group, the lead-exposed groups showed significantly higher lead concentrations in the serum, cortex, hippocampus, choroid plexus, CSF, and bones (P < 0.05) and significantly higher copper concentrations in the CSF, choroid plexus, serum, and hippocampus (P < 0.05). Confocal images showed that Ctr1 protein was expressed in the cytoplasm and cell membrane of choroid plexus in control group. However, Ctr1 migrated to CSF surface microvilli after lead exposure. Ctr1 fluorescence intensity gradually increased with increasing dose of lead, except that the middle-dose group had a higher Ctr1 fluorescence intensity than the high-dose group. In addition, the middle- and high-dose groups showed a lower ATX1 fluorescence intensity compared with the control group. Real-time PCR data indicated that the three lead-exposed groups showed significantly higher mRNA levels of Ctr1 and ATP7A compared with the control group (P < 0.05). CONCLUSION: Copper homeostasis in the choroid plexus is affected by lead exposure to induce copper homeostasis disorders in brain tissue, which may be one of the mechanisms of lead neurotoxicity.

[Disorder of copper homeostasis induced by lead exposure among mice and intervention effect of quercetin].

OBJECTIVE: To investigate the effect of lead exposure on copper and copper metalloenzyme and the intervention effect of quercetin. METHODS: Twenty-four specific pathogen-free male Sprague-Dawley rats of good health were randomly divided into control group (n = 8), lead acetate group (n = 8), and lead acetate + quercetin group (n = 8). The rats in lead acetate group were poisoned by drinking water with 1 g/L lead acetate for 8 weeks, while the rats in control group were fed by drinking water with sodium acetate of the same volume for 8 weeks; the rats in lead acetate+quercetin group were intraperitoneally injected with quercetin (30 mg × kg-1 × d-1) for 8 weeks while drinking water with lead acetate. The Morris water maze was used to test the learning and memory abilities of rats. The lead and copper levels in the serum, hippocampus, cortex, and bone were measured by graphite furnace atomic absorption spectrometry. The level of advanced glycation end products, activity of Cu/Zn superoxide dismutase (SOD), and content and activity of ceruloplasmin (CP) in the hippocampus and serum were measured using a test kit. HE staining was performed to observe the pathological changes in the hippocampus. RESULTS: The Morris water maze test showed that the latency in lead acetate group (52.50±12.04 s) was significantly longer than that in control group (28.08±7.31 s) (P<0.05), and the number of platform crossings was significantly lower in the lead acetate group than in the control group. Compared with those in the control group, the lead levels in the cortex and hippocampus in lead acetate group increased 2.72-fold and 3.79-fold, and the copper in the cortex and hippocampus, and serum free copper levels in lead acetate group increased 1.15-fold, 1.48-fold, and 6.44-fold. Compared with the control group, the lead acetate group had a lower content of CP in the hippocampus (1.23±0.40 U/mg provs0.78±0.08 U/mg pro) and 31.81%and 19.49%decreases in CP content and Cu/Zn SOD activity. Free copper level in serum was positively correlated with the latency and lead levels in the serum, cortex, and hippocampus. The escape latency of rats in lead acetate + quercetin group was decreased by 42.15% (P<0.05). The lead levels in the cortex and hippocampus in lead acetate + quercetin group (0.246 ± 0.58 µg/g and 0.202±0.049 µg/g) were significantly lower than those in lead acetate group (0.391±0.49 µg/g and 0.546±0.120 µg/g), but the free copper and copper levels in the hippocampus and cortex were not significantly reduced. The lead acetate + quercetin group had higher Cu/Zn SOD activity and CP content in the hippocampus than the lead acetate group (P < 0.05). The light microscope observation showed that the number of cells in the hippocampus was reduced with disordered arrangement in the lead acetate group; with quercetin intervention, the hippocampus damage was reduced. CONCLUSION: Lead exposure results in disorder of copper homeostasis, while quercetin may alleviate the damage induced by lead to some extent.

[The change of pulmonary surfactant protein of rat following silica exposure].

OBJECTIVE: To investigate the change of lung surfactant protein (SP) A,B,C,D of rats following silica dust exposure in order to provide the evidences for the early diagnosis indices or therapy of silicosis. METHODS: 60 male SD rats were randomly divided into silica group, and corresponding controls group. Rats in silica group were administrated 1 ml silica solution by intratracheal instillation at dose of 50 mg/ml. Rats in control group were administrated the same amount saline. At 3rd, 7th, 14th, 21st, 28th after silica exposure, serum and bronchoalveolar lavage fluid (BALF) samples were obtained. The concentration of SP-A, SP-B, SP-C, SP-D in serum and BALF were measured by using enzyme immunoassay (ELISA). Meanwhile the levels of total anti-oxidative activity (T-AOC) and hydroxyproline (HYP) in lung tissue were also detected. The pathology of lung tissue was conducted. RESULTS: Compared with control group, SP-A concentration in BALF of silica exposed rat for 3, 14, 21, 28d was significant lower and SP-D concentration in BALF of silica exposed rat for all time points was also lower. The differences were significant (P < 0.05). Meanwhile SP-B level in 7, 14, 21, 28 d silica exposed rats BALF and SP-C level in 14, 21, 28 d silica exposed rats markedly decreased (P < 0.05). In addition compared with control group, SP-A, SP-B and SP-C concentration in serum of silica exposed rat were higher when SP-A for 14, 21, 28 d silica exposure, SP-B for 7, 14, 21 d silica exposure and Sp-C for 7, 14, 21, 28 d exposure. And all difference were significant (P < 0.05). As silica exposure time increased, SP-C concentration in serum showed an increase trend, which showed a time-response relationship (r = 0.618, P = 0.042). However, SP-D concentration in serum of rat for 7, 14, 21, 28d silica exposure were significant lower than that of control group (P < 0.005). And there was a decrease trend with time point exposure regarding of SP-D (r = -0.731, P = 0.016). The HYP content in lung tissue of experiment rats increased at 3rd, 7th, 14th, 21st and 28th day time point and The T-AOC activity in lung tissue decrease at, 7th, 14th, 21st and 28th day time point. The differences were significant (P < 0.05). There was a positive correlation (P = 0.803, P = 0.045) between SP-C in BALF and HYP of silica exposed rats and a negative correlation between SP-D in BALF and HYP (r = -0.867, P = 0.033). No significant correlation were seen between SP-A, SP-B BALF and HYP (y = 0.416, P = 0.28; r = 0.592, P = 0.071). SP-C concentration in BALF and serum all showed an increased trend and a positive correlation was seen (r = 0.539, P = 0.046). The same decrease trend was seen between SP-D in BALF and serum and correlation value was 0.870 (P = 0.034). CONCLUSION: The silica exposure did cause the change of SP content both in BALF and serum. The SP-C and SP-D content in serum might be served as an early effective biomarker of silicosis.

[Effects of acrylamide on the permeability of blood cerebrospinal fluid barrier in rats].

OBJECTIVE: To explore the effects of acrylamide on the permeability of blood cerebrospinal fluid barrier (BCB) and tight junction protein ZO-1 of choroid plexus in rats and to provide a theoretical basis for explaining the mechanism of nerve injury induced by acrylamide. METHODS: Thirty two male Sprague-Dawley rats were randomly divided into ACR and control groups. ACR group was exposed to 20 mg/kg ACR daily for 5 days a week by intraperitoneal injection (i.p.) for 4 weeks. Control group was exposed to normal saline. The neurobehavioral tests (including sensatory and motor functions) were performed every week. At the end of exposure, Evan blue (EB) and Sodium fluorescein (NaFI) content in rat CSF were detected for determining the BCB permeability, Real-time PCR was used to measure the expression levels of ZO-1 mRNA in the epithelium cells of choroid plexus, and laser scanning confocal microscope (LSCM) was utilized to observe the distribution of ZO-1 protein. RESULTS: Neurobehavioral tests showed that the tail-flick latencies of ACR group were 27.77% and 53.71% as long as control group in the 3rd week and 4th week, respectively (P < 0.05). The hind lamb splay distances of ACR group were 131.76% and 153.77% as long as control group in the 3rd week and 4th week, respectively (P < 0.05). Evan blue (EB) and Sodium fluorescein (NaFI) content of ACR group were significantly higher than those of control group (P < 0.05). In the 4th week, the expression level of ZO-1 mRNA in ACR group was 0.21 +/- 0.07, which was significantly lower than that (0.31 +/- 0.11) in control group (P < 0.05). In the 4th week, the ZO-1 protein expression level of choroid plexus in ACR group was significantly lower than that in control group (P < 0.05). CONCLUSION: Acrylamide could increased the BCB permeability of rats, which may be involved in the central nervous injury induced by ACR.

The Evaluation Value of Diffusion-Weighted Imaging for Brain Injury in Patients after Deep Hypothermic Circulatory Arrest.

Objective: Cerebral complications may occur after surgery with deep hypothermic circulatory arrest (DHCA). Diffusion-weighted imaging (DWI) has shown promising results in detecting early changes of cerebral ischemia. However, studies in human models are limited. Here, we examined the significance of DWI for detecting brain injury in postoperative patients after DHCA. Methods: Twelve patients who had undergone selective cerebral perfusion with DHCA were enrolled. All patients underwent magnetic resonance imaging (MRI) examinations before and after the operation with T1-weighted phase (T1W) and T2-weighted phase (T2W). Magnetic resonance angiography (3D TOF) was applied to observe intracranial arterial communication situations. DWI was employed to calculate the apparent diffusion coefficient (ADC) values. The neurocognitive function of patients was assessed preoperatively and postoperatively using the Montreal Cognitive Assessment Scale (MoCA), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA). Results: The ADC values of the whole brain of patients after surgery were significantly higher than before surgery (P = 0.003). However, no significant difference in the ADC values of other regions before and after the operation was observed. There was no significant effect on the postoperative cognitive function of patients after surgery, but visual-spatial and executive abilities were significantly reduced, while psychological anxiety (P = 0.005) and depression levels (P < 0.05) significantly increased. Correlation analysis revealed a significant association between ADC change values and depression change values (P < 0.05). Conclusion: DHCA demonstrated no significant effect on the cognitive function of patients but could affect the mood of patients. On the other hand, DWI demonstrated promising efficiency and accuracy in evaluating brain injury after DHCA.

Lanthanum Impairs Learning and Memory by Activating Microglia in the Hippocampus of Mice.

Lanthanum can induce neurotoxicity and impair cognitive function; therefore, research on the mechanism by which the ability to learning and memory is decreased by lanthanum is vitally important for protecting health. Microglia are a type of neuroglia located throughout the brain and spinal cord that play an important role in the central nervous system. When overactive, these cells can cause the excessive production of inflammatory cytokines that can damage neighboring neurons. The purpose of this study was to explore the effect of lanthanum in the form of lanthanum chloride (LaCl3) on learning and the memory of mice and determine whether there is a relationship between hippocampal neurons or learning and memory damage and excessive production of inflammatory cytokines. Four groups of pregnant Chinese Kun Ming mice were exposed to 0, 18, 36, or 72 mM LaCl3 in their drinking water during lactation. The offspring were then exposed to LaCl3 in the breast milk at birth until weaning and then exposed to these concentrations in their drinking water for 2 months after weaning. The results showed that LaCl3 impaired learning and memory in mice and injured their neurons, activated the microglia, and significantly overregulated the mRNA and protein expression of tumor necrosis factor alpha, interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein-1, and nitric oxide in the hippocampus. The results of this study suggest that lanthanum can impair learning and memory in mice, possibly by over-activating the microglia.

Action of the Nrf2/ARE signaling pathway on oxidative stress in choroid plexus epithelial cells following lanthanum chloride treatment.

Lanthanum (La) can damage the blood brain barrier when it enters the brain tissue, causing learning and memory dysfunction. Currently, few studies have focused on La-induced oxidative stress in choroid plexus epithelial cells, which can severely impair the normal function of the blood-cerebrospinal fluid barrier (BCSFB) and ultimately cause central nervous system dysfunction. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element(ARE) signaling pathway is one of the major antioxidant systems and is vital in protecting cells against oxidative injury in rodents. In this study, Z310 cells were employed to construct BCSFB in vitro and treated with lanthanum chloride (LaCl3); meanwhile, 40 µmol/L tert-butylhydroquinone and the corresponding concentration of LaCl3 was used as the intervention groups. The results showed that LaCl3 treatment markedly decreased Z310 cell viability, increased the necrosis rate, and then reduced the transepithelial electrical resistance value of BCSFB in vitro; reactive oxygen species levels gradually increased, catalase and glutathione peroxidase activities decreased; furthermore, Nrf2 was significantly downregulated, and the expression of Nrf2 downstream genes such as heme oxygenase1, NADP(H): dehydrogenase quinone1, glutathione thiotransferase etc. noticeably decreased; in addition, interleukin-1ß and tumour necrosis factor-α associated with Nrf2 activation noticeably increased. However, tert-butylhydroquinone could activate the Nrf2/AER signaling pathway and attenuate the Z310 cell oxidative damage induced by LaCl3. Thus, the Nrf2/ARE signaling pathway is probably involved in weakening the BCSFB in vitro that is created by La-induced oxidative stress. Tert-butylhydroquinone can activate this pathway to reverse severe oxidative damage, which significantly strengthen the function of BCSFB.

Risk factors of postoperative acute kidney injury in patients with complex congenital heart disease and significance of early detection of serum transcription factor Nkx2.5.

OBJECTIVE: This study was designed to investigate the risk factors of postoperative acute kidney injury (AKI) in patients with complex congenital heart disease (CHD) and the significance of early detection of serum transcription factor Nkx2.5. METHODS: A total of 121 CHD patients admitted to the Shengli Clinical Medical College of Fujian Medical University were selected as study participants, among whom 69 patients with AKI after cardiac surgery were set as the research group (RG), and the rest of the 52 patients without AKI were set as the control group (CG). Cardiopulmonary bypass (CPB) duration, aortic occlusion time, postoperative creatinine (Cr) level and mechanical ventilation (MV) time were compared between the two groups. The expression and clinical significance of Nkx2.5 in the two groups were detected. Intensive Care Unit (ICU) residence time and total hospital stay were compared, and the risk factors were analyzed. RESULTS: The RG presented remarkably longer CPB duration and aortic occlusion time, evidently higher postoperative Cr level and longer MV time, and observably lower Nkx2.5 level in comparison to the CG (all P<0.05). According to the analysis of receiver operating characteristic (ROC) curves, Nkx2.5 displayed a favorable diagnostic value in predicting the occurrence of CHD complicated with AKI. ICU residence time and total hospital stay were longer in the RG than in the CG (P<0.05). CPB time and aortic occlusion time were independent risk factors for AKI in CHD patients, while surgical methods and Nkx2.5 detection were independent protective factors (P<0.05). CONCLUSIONS: CPB time, aortic occlusion time and surgical methods, as well as Nkx2.5 detection are independent factors affecting AKI in patients with CHD. Early detection of serum transcription factor Nkx2.5 is of particular importance for clinical diagnosis of CHD patients complicated with AKI.

The Role of Nrf2 on the Cognitive Dysfunction of High-fat Diet Mice Following Lead Exposure.

Lead (Pb) exposure can induce the severe deleterious damage on the central nervous system (CNS). High-fat diet also has been suggested that it had some adverse effects on learning and memory, cognitive function, but there is lack of study on Pb and high-fat diet co-exposure on the CNS damage. In this study, the goal was to explore the effect of Pb on the cognitive function of mice with high-fat diet and to investigate whether Nrf2 signaling pathway acts in the cerebral cortex. C57BL/6J mice were randomly divided into control, high-fat diet, Pb (drinking water with 250 mg/L lead acetate), and high-fat diet with Pb (drinking water with 250 mg/L lead acetate) co-exposure groups for 12 weeks. Experiment data showed that learn memory and exploration ability of mice obviously decreased in Pb and high-fat diet, and reactive oxygen species (ROS) increased; then, the protein expressions of Nrf2, heme oxygenase-1, NADP(H):dehydrogenase quinone 1, and superoxide dismutase 2 were lower significantly compared with those in the control group. This study suggested that down-expressed Nrf2 signaling pathway possibly related to the cognitive dysfunction induced by Pb and high-fat diet co-exposure.

Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes.

Emerging evidence suggests that a high level of circulating heat shock protein 70 (HSP70) correlates with a lower risk of vascular disease; however, the biological significance of this inverse relationship has not been explored. Herein, we report that oxidative low density lipoprotein (Ox-LDL) and homocysteine (Hcy) induce HSP70 release from endothelial cells. In rat endothelial cells, Ox-LDL and Hcy induced robust release of HSP70, independent of the classical route of endoplasmic reticulum/Golgi protein trafficking or the formation of lipid rafts. In contrast, Ox-LDL and Hcy significantly enhanced the exosomal secretory rate and increased the HSP70 content of exosomes. Exogenous HSP70 had no impact on LPS-, Ox-LDL- and Hcy-induced activation of endothelial cells, whereas HSP70 did activate monocytes alone, resulting in monocyte adhesion to endothelial cells. These results indicate that exosome-dependent secretion of HSP70 from endothelial cells provides a novel paracrine mechanism to regulate vascular endothelial functional integrity.

Lanthanum chloride induces neuron damage by activating the nuclear factor-kappa B signaling pathway in activated microglia.

Lanthanum is a rare earth element which can have adverse effects on the central nervous system (CNS). However, the mechanisms of these effects are not fully understood. The activated microglia plays an important role in the pathogenesis of neurodegenerative diseases and thus could be involved in mediating the toxic effects of lanthanum on the CNS. Nuclear factor-kappa B (NF-κB) is a critical nuclear factor which regulates the expression of inflammatory mediators in the activated microglia. This study investigated the effects of lanthanum chloride (LaCl3) on the NF-κB signaling pathway and explored the relationship between the microglia activation and neuron damage induced by La in vitro. The results showed that BV2 microglial cells treated with 0, 0.05, 0.1 or 0.2 mM LaCl3 could up-regulate the expression of Iba1 protein, a marker of microglia activation, and of p-IKKαß and p-IκBα in a dose-dependent manner. La could also increase the translocation of the NF-κB p65 subunit from the cytosol into the nucleus, and then elevate the production of NO, TNF-α, IL-1ß, IL-6 and MCP-1 by BV2 microglial cells. In a neuron-microglia co-culture system, BV2 microglia treated with LaCl3 resulted in a significant increase of the rates of neuron apoptosis. Conversely, the pre-treatment with PDTC (an inhibitor of the NF-κB signaling pathway) could inhibit the release of inflammatory cytokines and reduce the number of apoptotic neurons caused by La. These findings suggested that the neuron injury induced by LaCl3 might be related to the abnormal activation of microglia, which could remarkably increase the expression and release of pro-inflammatory cytokines via activating the NF-κB signaling pathway.

Diet-induced elevation of circulating HSP70 may trigger cell adhesion and promote the development of atherosclerosis in rats.

Although accumulating evidence indicates that heat shock protein 70 (HSP70) could be secreted into plasma and its levels have been found to have an ambiguous association with atherosclerosis, our knowledge for the exact role of circulating HSP70 in the development of atherosclerosis is still limited. In the present study, we report an adhesion-promoting effect of exogenous HSP70 and evaluate the potential involvement of elevated circulating HSP70 in the development of atherosclerosis. Time-dependent elevation of plasma HSP70 was found in diet-induced atherosclerotic rats, whose effect was investigated through further in vitro experiments. In rat aortic endothelial cell (RAEC) cultures, exogenous HSP70 incubation neither produced cell injuries by itself nor had protective effects on cell injuries caused by Ox-LDL or homocysteine. However, exogenous HSP70 administration could lead to a higher adhesion rate between rat peripheral blood monocytes (PBMCs) and RAECs. This adhesion-promoting effect appeared only when PBMCs, rather than RAECs, were pretreated with HSP70 incubation. PBMCs in an HSP70 environment released more IL-6 to supernatant, which subsequently up-regulated the expression of ICAM-1 in RAECs. These results indicate that the diet-induced elevation of circulating HSP70 could trigger cell adhesion with the help of IL-6 as a mediator, which provides a novel possible mechanism for understanding the role of circulating HSP70 in the pathogenesis of atherosclerosis.

Comparison of the anti-inflammatory active constituents and hepatotoxic pyrrolizidine alkaloids in two Senecio plants and their preparations by LC-UV and LC-MS.

Two Senecio plants, Senecio cannabifolius Less. and its variety S. cannabifolius Less. var. integrifolius (Kiodz.) Kidam., were both used as the raw material of Feining granule, a traditional Chinese medicine product for treating respiratory diseases. In this study, the chemical profiles of these two plants were investigated and compared by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). A total number of 83 constituents, including 55 organic acids, 11 flavonoids, 4 alkaloids, 3 terpenes and 10 other types of compounds, were characterized. The results indicated that the levels of most flavonoids were higher in S. cannabifolius than in S. cannabifolius var. integrifolius, however, the levels of hepatotoxic pyrrolizidine alkaloids (PAs) were higher in S. cannabifolius var. integrifolius than in S. cannabifolius. Fifteen constituents were evaluated on lipopolysaccharides (LPS) induced RAW 264.7 cells, and eleven of them showed inhibition effect against nitric oxide (NO) production. Finally, the levels of ten major constituents (including seven anti-inflammatory active ones) and two PAs in Feining granule from two Senecio plants were determined and compared by the LC-UV and LC-MS methods, respectively. It was found that one organic acid (homogentisic acid) and two PAs (seneciphylline and senecionine) had higher contents in the preparation of S. cannabifolius var. integrifolius than in that of S. cannabifolius, however, the situations were inverse for the levels of four organic acids and flavonoids (chlorogenic acid, hyperoside, isoquercitrin, and isochlorogenic acid B). Based on the above results, S. cannabifolius might be a better raw material for Feining granule than S. cannabifolius var. integrifolius, because it contained more anti-inflammatory constituents and less hepatotoxic PAs than the latter. However, more pharmacological evaluations should be carried out to support the selection. The results in this study were helpful for the quality control of Feining granule.

Acrylamide exposure impairs blood-cerebrospinal fluid barrier function.

Previous studies show that chronic acrylamide exposure leads to central and peripheral neu-ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospinal fluid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal fluid was increased and the cerebrospinal fluid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal fluid/serum albumin ratio was increased on day 28 after exposure. Our findings show that acrylamide exposure damages the blood-cerebrospinal fluid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity.