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Biomedical subjects

Lin Xu

Publications and source records attributed to Lin Xu.

At least 55 records · Page 3Linked to original sources

Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring.

Clinical studies demonstrate that prenatal stress causes cognitive deficits and increases vulnerability to affective disorders in children and adolescents. The underlying mechanisms are not yet fully understood. Here, we reported that prenatal stress (10 unpredictable, 1 s, 0.8 mA foot shocks per day during gestational days 13-19) impaired long-term potentiation (LTP) but facilitated long-term depression (LTD) in hippocampal CA1 region in slices of the prenatal stressed offspring (5 weeks old). Cross-fostering neonate offspring by the prenatal stressed or control mothers did not change the effects of prenatal stress on the hippocampal LTP and LTD. Furthermore, prenatal stress enhanced the effects of acute stress on the hippocampal LTP and LTD and impaired spatial learning and memory in the Morris water maze in the young rat offspring. Therefore, prenatal stress alters synaptic plasticity and enhances the effects of acute stress on synaptic plasticity in the hippocampus, which may be the mechanism for the impaired spatial learning and memory in young rat offspring.

Animals↗

Morphine conditioned place preference depends on glucocorticoid receptors in both hippocampus and nucleus accumbens.

Learned association between drugs of abuse and context is essential for the formation of drug conditioned place preference (CPP), which is believed to engage many brain regions including hippocampus and nucleus accumbens (NAc). The underlying mechanisms are not fully understood. Here, we examined whether glucocorticoid receptors (GRs) of hippocampus and NAc influenced the formation of morphine CPP in Sprague Dawley rats. We found that systemic or intrahippocampal infused DMSO vehicle (DMSO 20% in saline) 30 min before daily morphine (10 mg/kg, s.c.) conditioning did not affect the formation of morphine CPP. In contrast, systemic administration (5 mg/kg, s.c.) or intrahippocampal infusion (0, 0.1, 1.0, 10, 20 microg per side) of the GR antagonist RU38486 blocked or impaired the formation of CPP in a dose-dependent manner, respectively. Furthermore, intra-NAc infused RU38486 (10 microg per side) but not DMSO vehicle also prevented the formation of CPP. These results demonstrate that both the GRs of hippocampus and NAc are necessary for the formation of morphine CPP, suggesting a neural network function of the GRs in forming the opiate-associated memory.

Animals↗

Stress evoked by opiate withdrawal facilitates hippocampal LTP in vivo.

Stress impairs hippocampal long-term potentiation (LTP), but it is unknown whether the stress evoked by opiate withdrawal has the same effect. Here the authors report that opiate withdrawal for 4 days does not influence basal synaptic transmission, but results in a greatly increased LTP in hippocampal CA1 area in anesthetized rats. Elevated-platform stress enabled a large LTP in rats withdrawn for only 18 h, but the glucocorticoid receptor antagonist RU38486 (twice per day for 3 days) prevented the large LTP on 4 days withdrawal. Moreover, 4 days withdrawal enhanced the NMDAR-mediated EPSCs, in which the NR2A-containing NMDAR-mediated EPSC was increased but the NR2B-containing NMDAR-mediated EPSC was decreased. These results suggest that adaptive changes of the NMDAR and glucocorticoid receptor functions during 4 days of opiate withdrawal may enable stress to facilitate hippocampal LTP, potentially contributing to the opiate withdrawal experience-dependent modifications of hippocampal functions.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Crossed polydactyly type I caused by a point mutation in the GLI3 gene in a large Chinese pedigree.

Polydactyly is one of the most common forms of congenital malformation in humans, and is displayed by 119 disorders. Crossed polydactyly (CP) is defined as the coexistence of preaxial and postaxial polydactyly with a difference in the axes of polydactyly between the hands and feet. In an effort to map the gene responsible for CP, we studied a seven-generation Chinese family of 56 individuals, 28 of whom were affected. A thorough search with highly informative polymorphic markers showed no recombination among the affected members with the markers on chromosome 7p15-q11.23, but no linkage with chromosomes 2q31, 7q36, 13q, and 19p. Mutation analysis showed a substitution mutation of 1927C --> T in exon 12 of the GLI3 gene, which is predicted to pretruncate the GLI3 protein. This mutation has variable phenotypes of polydactyly, indicating that other genetic factors also contribute to the diversity of polydactyly phenotypes. Our results increase the phenotypic spectrum caused by GLI3 mutations and are important for the analysis and understanding of the etiology of these limb malformations.

Asian People↗

Binocular status after surgery for constant and intermittent exotropia.

PURPOSE: To investigate whether constant exotropia patients with a previous history of intermittent exotropia X(T), like X(T) patients, can achieve postoperative bifixation, and whether they have a better postoperative sensory outcome than those without previous history of X(T). DESIGN: Prospective comparative clinical study. METHODS: Sixty-three consecutive patients with intermittent or constant exotropia were divided into three groups: X(T) (group 1), constant exotropia with a previous history of X(T) (group 2), and constant exotropia without previous history of X(T) (group 3). The surgical outcomes were assessed and compared in motor and sensory terms separately between the three groups. Successful motor alignment was defined as within 8 prism diopters (PD) (exo or eso). A stereoacuity < or =60 seconds of arc was considered as bifixation, and a stereoacuity < or =800 seconds of arc was considered as gross stereopsis. RESULTS: The successful motor alignment rates of group 1, group 2, and group 3 were 79%, 71%, and 67%, respectively (group 1 vs group 2, P = .826; group 1 vs group 3, P = .551; group 2 vs group 3, P = 1.000). Twenty-five (74%) patients in group 1 achieved bifixation and none achieved in group 2 or group 3 (group 1 vs group 2, P = .001; group 1 vs group 3, P = .001). Meanwhile, 34 patients (100%) in group 1, 11 (79%) in group 2, and 5 (33%) in group 3 achieved gross stereopsis (group 1 vs group 2, P = .021; group 2 vs group 3, P = .025; group 1 vs group 3, P = .001). Compared with patients in the two constant exotropia groups, patients in X(T) group had a significantly better sensory outcome in both bifixation and gross stereopsis. Patients in group 2 had a better sensory outcome than those in group 3 in gross stereopsis. CONCLUSIONS: Constant exotropia patients with a previous history of X(T) have a better postoperative sensory outcome in gross stereopsis than those without previous history of X(T), but a worse surgical sensory outcome when compared with X(T) patients in both bifixation and gross stereopsis. Constant exotropia patients decompensated from X(T) may have missed the best time for treatment.

Adolescent↗

Plant fertility defects induced by the enhanced expression of microRNA167.

The plant hormone auxin plays a critical role in regulating plant growth and development. Recent advances have been made in the understanding of auxin response pathways, primarily by the characterization of auxin response mutants in Arabidopsis. In addition, microRNAs (miRNAs) have been shown to be critical regulators of genes important for normal plant development and physiology. However, little is known about possible interactions between miRNAs and hormonal signaling during normal development. Here we show that an Arabidopsis microRNA, miR167, which has a complementary sequence to a portion of the AUXIN RESPONSE FACTOR6 (ARF6) and ARF8 mRNAs, can cause transcript degradation for ARF8, but not for ARF6. We report phenotypic characterizations of 35S::MIR167b transgenic lines, and show that severe 35S::MIR167b transgenic lines had phenotypes similar to those of an arf6 arf8 double mutant. The transgenic phenotypes suggest that miR167 may repress ARF6 at the level of translation. We demonstrate that the transgenic plants are defective in all four whorls of floral organs. In the transgenic flowers, filaments were abnormally short, anthers could not properly release pollen, and pollen grains did not germinate. Our results provide an important link between the miRNA-mediated regulatory pathway of gene expression and the auxin signaling network promoting plant reproductive development.

Arabidopsis↗

Hypertension after experimental cerebral ischemia: candesartan provides neurovascular protection.

BACKGROUND: After ischemic stroke, hypertension increases the risk of recurrence, hemorrhage and fatal cerebral edema, but blood pressure (BP) lowering in the acute stroke period is controversial due to fears of infarct extension and worsened outcomes. OBJECTIVE: To determine whether BP lowering with candesartan, initiated at reperfusion, can reduce neurovascular damage and improve outcome in a model of hypertension after experimental ischemic stroke. METHODS: Male Wistar rats (280-305 g) underwent 3 h of middle cerebral artery occlusion (MCAO). At reperfusion, either saline (n = 18) or candesartan 1 mg/kg (n = 18) was administered intravenously. BP was measured by telemetry for 2 days before and 24 h after MCAO. Neurologic function was assessed and sacrifice occurred at 24 h after occlusion. Brain tissue was analyzed for infarct size, hemoglobin content and edema. RESULTS: Mean BP increased from 96 to 124 mmHg immediately upon MCAO and decreased to 114 mmHg after reperfusion, remaining elevated for 24 h (P < 0.001) in the saline group. Candesartan reduced BP back to baseline and BP remained lower than in saline-treated animals until sacrifice (P < 0.001). Infarct size (54 versus 38%, P = 0.01) and hemoglobin content (23.4 versus 10.0 microg/g tissue; P = 0.03) and edema (17.97 versus 11.33%, P < 0.0001) were lower in the candesartan group. In addition, neurologic function at 24 h was improved (P = 0.0036) in the candesartan group. CONCLUSIONS: Candesartan administered after reperfusion in acute ischemic stroke reduces neurovascular damage and improves outcome.

Animals↗

Role of the luxS quorum-sensing system in biofilm formation and virulence of Staphylococcus epidermidis.

Nosocomial infections caused by Staphylococcus epidermidis are characterized by biofilm formation on implanted medical devices. Quorum-sensing regulation plays a major role in the biofilm development of many bacterial pathogens. Here, we describe luxS, a quorum-sensing system in staphylococci that has a significant impact on biofilm development and virulence. We constructed an isogenic DeltaluxS mutant strain of a biofilm-forming clinical isolate of S. epidermidis and demonstrated that luxS signaling is functional in S. epidermidis. The mutant strain showed increased biofilm formation in vitro and enhanced virulence in a rat model of biofilm-associated infection. Genetic complementation and addition of autoinducer 2-containing culture filtrate restored the wild-type phenotype, demonstrating that luxS repressed biofilm formation through a cell-cell signaling mechanism based on autoinducer 2 secretion. Enhanced production of the biofilm exopolysaccharide polysaccharide intercellular adhesin in the mutant strain is presumably the major cause of the observed phenotype. The agr quorum-sensing system has previously been shown to impact biofilm development and biofilm-associated infection in a way similar to that of luxS, although by regulation of different factors. Our study indicates a general scheme of quorum-sensing regulation of biofilm development in staphylococci, which contrasts with that observed in many other bacterial pathogens.

Animals↗

Transplantation of cryopreserved human bone marrow-derived multipotent adult progenitor cells for neonatal hypoxic-ischemic injury: targeting the hippocampus.

There is currently no treatment for neonatal hypoxic-ischemic (HI) injury. Although limited clinical trials of stem cell therapy have been initiated in a number of neurological disorders, the preclinical evidence of a cell-based therapy for neonatal HI injury remains in its infancy. Stem cell therapy, via stimulation of endogenous stem cells or transplantation of exogenous stem cells, has targeted neurogenic sites, such as the hippocampus, for brain protection and repair. The hippocampus has also been shown to secrete growth factors, especially during the postnatal period, suggesting that this brain region presents a highly conducive microenvironment for cell survival. Based on its neurogenic and neurotrophic factor-secreting features, the hippocampus stands as an appealing target for stem cell therapy. In the present study, we investigated the efficacy of intrahippocampal transplantation of multipotent adult progenitor cells (MAPCs), which are pluripotent progenitor cells with the ability to differentiate into a neuronal lineage. Seven-day old Sprague-Dawley rats were initially subjected to unilateral HI injury, that involved permanent ligation of the right common carotid artery and subsequent exposure to hypoxic environment. At day 7 after HI

Animals↗

The relationship between plasma osteoprotegerin and endothelium-dependent arterial dilation in type 2 diabetes.

Osteoprotegerin is a recently identified inhibitor of bone resorption. Recent studies indicate that osteoprotegerin also acts as an important regulatory molecule in the vasculature. The purpose of this study was to investigate the relationship between plasma osteoprotegerin levels and endothelium-dependent arterial dilation in type 2 diabetic patients. The study subjects included 40 newly diagnosed type 2 diabetic patients and 46 healthy subjects. All patients were given insulin therapy for 6 months. Plasma osteoprotegerin concentration was measured in duplicate by a sandwich enzyme-linked immunosorbent assay method, and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual glyceryltrinitrate. The plasma osteoprotegerin level in patients before treatment was 3.36 +/- 0.32 ng/l, which was significantly higher than that in control subjects (2.38 +/- 0.25 ng/l, P < 0.001). After 6 months of treatment, osteoprotegerin levels decreased markedly (2.83 +/- 0.34 ng/l, P < 0.001). Flow-mediated endothelium-dependent arterial dilation in patients before treatment was 3.21 +/- 0.52%, which was significantly lower than that in control subjects (4.46 +/- 0.56%, P < 0.01), and it improved markedly after 6 months of treatment (4.03 +/- 0.49%, P < 0.01). In multivariate analysis, osteoprotegerin was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), HbA(1c) (A1C), and ultrasensitive C-reactive protein (CRP) at baseline (P < 0.01). The absolute changes in osteoprotegerin showed significant correlation with changes in endothelium-dependent arterial dilation, FBG, A1C, and CRP in diabetic patients during the course of treatment (P < 0.01). This study shows that plasma osteoprotegerin levels are elevated in newly diagnosed diabetic patients and are significantly associated with endothelial function.

Adult↗

Behavioral and histological characterization of intrahippocampal grafts of human bone marrow-derived multipotent progenitor cells in neonatal rats with hypoxic-ischemic injury.

Children born with hypoxic-ischemic (HI) brain injury account for a significant number of live births wherein no clinical treatment is available. Limited clinical trials of stem cell therapy have been initiated in a number-of neurological disorders, but the preclinical evidence of a cell-based therapy for neonatal HI injury remains in its infancy. One major postulated mechanism underlying therapeutic benefits of stem cell therapy involves stimulation of endogenous neurogenesis via transplantation of exogenous stem cells. To this end, transplantation has targeted neurogenic sites, such as the hippocampus, for brain protection and repair. The hippocampus has been shown to secrete growth factors, especially during the postnatal period, suggesting that this brain region presents as highly conducive microenvironment for cell survival. Based on its neurogenic and neurotrophic factor-secreting features, the hippocampus stands as an appealing target for stem cell therapy. Here, we investigated the efficacy of intrahippocampal transplantation of multipotent progenitor cells (MPCs), which are pluripotent progenitor cells with the ability to differentiate into a neuronal lineage. Seven-day-old Sprague-Dawley rats were initially subjected to unilateral HI injury, which involved permanent ligation of the right common carotid artery and subsequent exposure to hypoxic environment. At day 7 after HI injury, animals received stereotaxic hippocampal injections of vehicle or cryopre-served MPCs (thawed just prior to transplantation) derived either from Sprague-Dawley rats (syngeneic) or Fisher rats (allogeneic). All animals were treated with daily immunosuppression throughout the survival period. Behavioral tests were conducted on posttransplantation days 7 and 14 using the elevated body swing test and the rotarod to reveal general and coordinated motor functions. MPC transplanted animals exhibited reduced motor asymmetry and longer time spent on the rotarod than those that received the vehicle infusion. Both syngeneic and allogeneic MPC transplanted injured animals did not significantly differ in their behavioral improvements at both test periods. Immunohistochemical evaluations of graft survival after behavioral testing at day 14 posttransplantation revealed that syngeneic and allogeneic transplanted MPCs survived in the hippocampal region. These results demonstrate for the first time that transplantation of MPCs ameliorated motor deficits associated with HI injury. In view of comparable behavioral recovery produced by syngeneic and allogeneic MPC grafts, allogeneic transplantation poses as a feasible and efficacious cell replacement strategy with direct clinical application. An equally major finding is the observation lending support to the hippocampus as an excellent target brain region for stem cell therapy in treating HI injury.

Animals↗

The experimental study of genetic engineering human neural stem cells mediated by lentivirus to express multigene.

OBJECTIVE: To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs) mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI). METHODS: Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3 (NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot. RESULTS: Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot. CONCLUSIONS: Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.

Animals↗

[Effects of simvastatin on DNA synthesis in rat cardiac fibroblasts].

OBJECTIVE: To investigate the effects of simvastatin (Sim) and the interference by mevalonate (MVA) against its effect on DNA synthesis in rat cardiac fibroblasts (CFs). METHODS: CFs were isolated from neonatal SD rats by trypsin digestion and growth-arrested CFs were stimulated with Sim and/or MVA at varied concentrations for different time lengths, and the DNA synthesis in the cells was measured by (3)H-thymidine ((3)H-TdR) incorporation assay. RESULTS: Sim decreased (3)H-TdR incorporation in the CFs in a concentration-dependent manner, and (3)H-TdR incorporation was significantly lower in cells treated with 1 x 10(-6) and 1 x 10(-5) mol/L Sim (1,175+/-202.66 and 771+/-164.86 cpm/2000 cells, respectively) than in the control cells (1,608+/-204.32 cpm/2000 cells, P<0.01). As the treatment time with 1 x 10(-5) mol/L Sim prolonged (for 6, 12, 18, 24, 36, 42, and 48 h), (3)H-TdR incorporation in CFs decreased gradually, showing an obvious inverse correlation with the treatment time (r=-919, P<0.01). (3)H-TdR incorporation in cells treated with 1 x 10(-6) to 1 x 10(-3) mol/L MVA and 1 x 10(-5) mol/L Sim rose steadily as MVA concentration increased. A significant difference in the incorporation was found between cells treated with both 1 x 10(-4)/1 x 10(-3) mol/L MVA and 1 x 10(-5) mol/L Sim (1,612+/-308.57 and 1,995+/-353.83 cpm/2000 cells, respectively) and the cells with 1 x 10(-5) mol/L Sim treatment alone (P<0.01); difference was also noted between cells treated with 1 x 10(-5) mol/L MVA and the control cells (P<0.05), but treatment with 1 x 10(-6) mol/L MVA did not produce much difference in comparison with the control cells (P>0.05) With the increase of treatment time (for 6, 12, 18, 24, 36, 42, 48 h), 1 x 10(-3) mol/L MVA caused steady increase in (3)H-TdR incorporation in the CFs, showing a significant positive correlation with the treatment time (r=0.968, P<0.01). CONCLUSION: Sim can decrease DNA synthesis in rat CFs and postpone the occurrence of myocardial fibrosis, which can be reversed by MVA.

Animals↗

[Autoantibodies against beta1 and M2 receptor in diabetic patients with refractory hypertension].

OBJECTIVE: To explore the role of the autoantibodies against M(2)-muscarinic receptor (M(2)-receptor), beta(1)-adrenergic receptor (beta(1)-receptor) in the development of diabetic with refractory hypertension. METHODS: Serum autoantibodies against M(2) and beta(1) were detected by ELISA using synthesized epitopes of the second extracellular loop of M(2) receptor (169 - 193) and beta(1) receptor (197 - 222) in healthy controls (n = 40), diabetic patients (n = 62), diabetic patients with non-refractory hypertension (n = 55) and diabetic patients with refractory hypertension (n = 81). RESULTS: The positive rates of the autoantibodies against M(2) receptor and beta(1) receptor were similar among healthy controls (15.0% and 17. 5%), diabetes mellitus patients (17.7% and 14.5%) and diabetic patients with non-refractory hypertension (16.4% and 12.7%) but are significantly higher in diabetic patients with refractory hypertension (64.2% and 55.6%, P < 0.01 vs. other 3 groups). CONCLUSION: This finding suggests that autoimmune mechanisms might play a role in the pathogenesis of diabetic patients with refractory hypertension.

Adult↗

[Comparative study of postoperative early enteral nutrition and parenteral nutrition in esophageal carcinoma].

OBJECTIVE: To investigate the effect of postoperative early enteral nutrition (EN) and parenteral nutrition (PN) on nutritional status and morbidity in esophageal carcinoma. METHODS: One hundred and six patients with esophageal carcinoma were randomly divided into two groups, and received enteral nutrition(n=53) or parenteral nutrition(n=53) continuously for 7 days after operation. The body weight, blood routine test, liver function, and morbidity on postoperative day 8 were compared with those before operation. RESULTS: The body weight, red blood cell count, and the levels of hemoglobin, serum albumin and transaminase decreased less in EN group than those in PN group(P< 0.01). The complication rates of anastomotic fistula, pulmonary infection, pleural effusion and delayed incision healing were 0, 5.7%, 3.8% and 0 in EN group, and 5.7%, 28.3%, 15.1% and 7.6% in PN group. There were significant differences between the two groups(P< 0.05). CONCLUSION: Early postoperative enteral nutrition after esophageal carcinoma surgery can improve nutritional status and reduce complications in comparison with parenteral nutrition.

Adult↗

[Effect of losartan on sarcoplasmic reticulum Ca2+ handing proteins in heart failure rabbit].

OBJECTIVE: To investigate the effects of losartan on mRNA expression of myocardial sarcoplasmic reticulum calcium handling proteins (SERCA2, RyR2 and PLB) and the role of which in prevention of chronic heart failure in rabbit. METHODS: After chronic heart failure was induced by ligation of the left anterior descending artery in rabbits, the animals were treated with losartan. At 8 weeks after ligation, left ventricular function, hemodynamic parameters, and SERCA2, RyR2, PLB mRNA expressions were observed. RESULTS: Compared with the control group (group C), LVEDP in the infarcted group (group I) increased (P < 0.01), while +dp/dt(max) and -dp/dt(max) decreased significantly (P < 0.01). LVEDP was lower but +dp/dt(max) and -dp/dt(max) significantly higher in the losartan treated group (group L) than those in group I (P < 0.05). SERCA2, RyR2, and PLB mRNA expressions in group I were remarkably lower than those in group L (P < 0.01) and group C (P < 0.01), respectively. CONCLUSION: Losartan can improve cardiac function, probably owing to its upregulating mRNA expressions of myocardial sarcoplasmic reticulum Ca(2+) handling proteins (RyR2, SERCA2 and PLB) in the prevention of heart failure.

Angiotensin II Type 1 Receptor Blockers↗

[The excision of right hemicolonic carcinoma with anterograde clearance to lymph nodes].

OBJECTIVE: To investigate the essentials of operation and the postoperative effect of right hemicolonic carcinoma with anterograde clearance of lymph nodes. METHODS: One hundred and thirty-five patients with right hemicolonic infiltrated carcinoma, who were eligible for radical excision (D(3)), were divided into 2 groups. Among them, the anterograde clearance of lymph nodes was performed on 56 cases; the retrograde clearance was performed on 79 cases. Both groups showed no significant difference in age, sex, Dukes' staging and pathological type. RESULTS: The average time of operation: the anterograde group was (180 +/- 40) min; the retrograde group was (180 +/- 20) min. The average amount of bleeding: the anterograde group was (200 +/- 80) ml; the retrograde group was (200 +/- 30) ml. The cleared number of lymph nodes: the anterograde group were 6.3 +/- 4.2, 2.6 +/- 3.1, 1.5 +/- 2.3 in paracolon, middle and radicel of vasorum respectively, the total number was 11.4 +/- 8.6; the retrograde group were 6.4 +/- 2.2, 2.8 +/- 2.1, 1.1 +/- 1.1 respectively, the total number was 10.8 +/- 5.6 (P > 0.05). The postoperative metastasis to liver: the anterograde group was 8 cases (13.9%); the retrograde group was 21 cases (26.6%, P < 0.05). The 5-year survival rate: the anterograde group was 72.8% (41/56); the retrograde group was 65.5% (52/79) (P < 0.05). CONCLUSIONS: The operative technique of the excision was little difficulty and complexity, and it could fit well with the requirement of non touch isolation, and act to cut down the postoperative metastasis to liver and to elevate 5-year survival rate.

Adult↗

Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead.

Acid-sensing ion channels (ASICs) are emerging as fundamental players in the regulation of neural plasticity and in pathological conditions. Here we showed that lead (Pb2+), a well known neurotoxic metal ion, reversibly and concentration-dependently inhibited ASIC currents in the acutely dissociated spinal dorsal horn and hippocampal CA1 neurons of rats. In vitro expression of ASIC subunits in combination demonstrated that both ASIC1 and -3 subunits were sensitive to Pb2+. Mechanistically, Pb2+ reduced the pH sensitivity of ASICs independent of membrane voltage change. Moreover, Pb2+ inhibited the ASIC-mediated membrane depolarization and the elevation of intracellular Ca2+ concentration. In addition, we compared the effect of Pb2+ with that of Ca2+ or amiloride to explore the possible interactions of Pb2+ and Ca2+ in regulating ASICs, and we found that Pb2+ inhibited ASIC currents independent of the amiloride/Ca2+ blockade. Because ASIC1b and -3 subunits are mainly expressed in peripheral neurons, our data identified ASIC1a-containing Ca2+-permeable ASIC as a novel central target of Pb2+ action, which may contribute to Pb2+ neurotoxicity.

Acid Sensing Ion Channels↗