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1.
Indian J Pathol Microbiol ; 66(4): 799-803, 2023.
Article in English | MEDLINE | ID: mdl-38084535

ABSTRACT

Context: Squalene epoxidase (SQLE) is overexpressed in a variety of tumors, which may play an important role in their tumorigenesis, development, and prognosis. Aims: The aim of this study is to investigate the expression of SQLE and explore its clinicopathological significance in gastric cancer. Settings and Design: The correlation between its positive expression and the pathological characteristics of patients (such as sex, age, tumor size, survival, tumor differentiation, TNM staging, and lymph node metastasis) was analyzed. Materials and Methods: Immunohistochemical method was used to detect its expression in 107 cases of gastric carcinoma and 34 cases of tumor-adjacent tissues. Statistical Analysis Used: Counting data were analyzed by Chi-square test. Its overall survival was analyzed by Kaplan-Meier method and log-rank test. Its hazard factors were analyzed by Cox multivariate analysis. Results: The positive rate of SQLE in gastric cancer is 67.3%, which is higher than that in tumor-adjacent tissues (17.6%), <0.001. Expression of SQLE is closely related to tumor differentiation, TNM staging and lymph node metastasis (P = 0.030, P = 0.009, and P = 0.011, respectively). Furthermore, compared with those low expression of SQLE, the patients of overexpression had worse overall survival by Kaplan-Meier analysis (P = 0.025). Cox multivariate analysis shows that lymph node metastasis, tumor differentiation, SQLE, and TNM staging are independent factors for prognosis of gastric cancer (P = 0.003, 0.020, 0.018, and P = 0.001 respectively). Conclusions: SQLE is overexpressed in gastric cancer. It could be used for the diagnosis and prognosis of the gastric cancer patients.


Subject(s)
Squalene Monooxygenase , Stomach Neoplasms , Humans , Clinical Relevance , Lymphatic Metastasis , Neoplasm Staging , Prognosis , Stomach Neoplasms/genetics
2.
J Food Sci ; 84(9): 2658-2665, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31441515

ABSTRACT

Hepatic injury is one of the most common digestive system diseases worldwide in clinic. Guanylic acid or guanosine monophosphate (GMP) was an important component of nucleotides, which is mainly in the form of sodium salt (disodium guanylate, GMP-Na2 ). However, its effect on hepatic injury has not yet been investigated. This study is to investigate the protective effects of GMP-Na2 on acute hepatic injury induced by carbon tetrachloride (CCl4 ), and to explore its mechanism. The hepatic injury models of mice and HL-7702 cells were induced by CCl4 . The alanine transaminase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (T-AOC) were determined by biochemical method. Hematoxylin-eosin staining were used to determine the morphological changes on liver tissue in mice. The mRNA and protein expressions of caspase-3, Bax, and Bcl-2 were detected by RT-PCR and Western blot analysis. Our results show that GMP-Na2 treatment significantly decreased the activities of ALT and AST, and the levels of MDA as well as increased the levels of SOD, GSH-Px, and T-AOC. Importantly, GMP-Na2 effectively enhanced the antiapoptosis function by upregulating Bcl-2 expression and downregulating caspase-3 and Bax expressions in vivo and in vitro. Moreover, the histopathological changes of liver tissue were obviously improved after GMP-Na2 treatment. These findings suggest that GMP-Na2 has protective effects on hepatic injury, and its mechanisms may be associated with antioxidative stress and antiapoptosis.


Subject(s)
Antioxidants/pharmacology , Apoptosis/drug effects , Carbon Tetrachloride/toxicity , Chemical and Drug Induced Liver Injury/metabolism , Guanosine Monophosphate/pharmacology , Liver/drug effects , Animals , Liver/metabolism , Mice , Oxidative Stress/drug effects
3.
Behav Modif ; 43(1): 82-114, 2019 01.
Article in English | MEDLINE | ID: mdl-29090595

ABSTRACT

Children with autism spectrum disorders (ASD) may not develop symbolic play skills, so such skills need to be taught specifically. We report an experiment regarding a procedure targeting "object-substitution" symbolic play skills. The "object-substitution" symbolic play behavior occurred when the child labeled a common object with the name of a substitute and used the object to perform a play action (e.g., As she put a bowl on her head, she called it a hat). A multiple probe across behaviors design was employed with five children (four boys and one girl, aged 3 to 6 years) with ASD. All children had verbal communication and demonstrated functional play and generalized imitation, but no symbolic play skills prior to the study. The instruction consisted of intraverbal training, picture prompts, and modeling of play actions. All children demonstrated object-substitution symbolic play skills after the instruction. The occurrences of response generalization were also discussed.


Subject(s)
Autism Spectrum Disorder/rehabilitation , Child Behavior , Imitative Behavior , Play and Playthings , Psychotherapy/methods , Child , Child, Preschool , Female , Humans , Male , Treatment Outcome
4.
Int J Clin Exp Pathol ; 12(8): 2959-2966, 2019.
Article in English | MEDLINE | ID: mdl-31934132

ABSTRACT

The purpose of this article is to study whether the overexpression of urokinase-type plasminogen activator (uPA) can promote the proliferation and fibrinolytic activity of human umbilical vein endothelial cells (HUVECs). The recombinant adenovirus vectors containing the human uPA gene were constructed and transfected into HUVECs. In this study, the mRNA of uPA was detected by qPCR, and the uPA protein was measured by Western blot. The cell proliferation was measured using MTT. The fibrinolytic activity of uPA was quantified using a colorimetric assay. We also measured MMP2 (metalloproteinase-2), MMP9 (metalloproteinase-9), and VEGF (vascular endothelial growth factor) proteins using ELISA. The results showed that the levels of the uPA mRNA and the protein in the overexpression group were significantly higher compared to the other groups, (P < 0.05). The cell proliferation and uPA activity were increased significantly in the overexpression group, compared to the other groups, (P < 0.05). The secretions of MMP2, MMP9, and VEGF in the overexpression group were significantly higher than they were in the other two groups (P < 0.05). In conclusion, we successfully transfected a recombined adenovirus vector carrying uPA into a HUVEC. The exogenous uPA gene could transcribe and secrete the uPA protein in the HUVECs. The overexpression of uPA can increase cell proliferation and uPA activity. It can improve the invasion and angiogenesis ability in HUVECs by promoting their secretions of MMP2, MMP9, and VEGF.

5.
Mol Med Rep ; 16(6): 9181-9188, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29039510

ABSTRACT

Atherosclerosis (AS) is a progressive disease of multifactorial origin, which occurs in response to endothelial injury. Increased homocysteine (Hcy) is considered a major cause of endothelial dysfunction, oxidative stress and DNA methylation; however, the mechanisms remain to be fully elucidated. The aim of the present study was to investigate whether Hcy causes injury to endothelial cells (ECs) by the effect of lectin­like oxidized­low density lipoprotein receptor­1 (LOX­1) DNA methylation through toll­like receptor 4(TLR4)/nuclear factor (NF)­κB/DNA methyltransferase (DNMT)1. The ECs were treated with different concentrations of Hcy, and it was found that Hcy promoted the expression of TLR4, leading to EC injury. The effect of oxidative stress was analyzed by measuring superoxide dismutase, malondialdehyde and hydrogen peroxide in the ECs. In addition, the association between NF­κB and DNMT1 was examined by treatment of the ECs with pyrrolidine dithiocarbamate (PDTC). The results suggested that Hcy induced LOX­1 DNA hypomethyaltion to promote the expression levels of LOX­1. Taken together, Hcy injured the ECs through the effect of methylation and trans­sulfuration metabolism of LOX­1 through TLR4/NF­κB/DNMT1. Following injury to the ECs, lipids, particularly ox­LDL, accumulated in the sub­endothelial layer to promote the formation of AS.


Subject(s)
DNA (Cytosine-5-)-Methyltransferase 1/metabolism , DNA Methylation , Endothelial Cells/metabolism , Homocysteine/metabolism , NF-kappa B/metabolism , Oxidative Stress , Scavenger Receptors, Class E/genetics , Toll-Like Receptor 4/metabolism , Biomarkers , Cells, Cultured , Endothelial Cells/drug effects , Gene Expression Regulation , Homocysteine/pharmacology , Humans , Hydrogen Peroxide , Lipoproteins, LDL , Superoxide Dismutase/metabolism , Toll-Like Receptor 4/genetics
6.
Mol Med Rep ; 16(5): 7775-7783, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28944836

ABSTRACT

Vascular smooth muscle cell (VSMC) proliferation is a primary pathological event in atherosclerosis (AS), and homocysteine (Hcy) is an independent risk factor for AS. However, the underlying mechanisms are still lagging. Studies have used the combination of methylation of promoters of multiple genes to diagnose tumors, thus the aim of the current study was to investigate the role of methylation status of several genes in VSMCs treated with Hcy. CpG islands were identified in the promoters of platelet­derived growth factor (PDGF), p53, phosphatase and tensin homologue on chromosome 10 (PTEN) and mitofusin 2 (MFN2). Hypomethylation was observed to occur in the promoter region of PDGF, hypermethylation in p53, PTEN and MFN2, and hypomethylation in two global methylation indicators, aluminium (Alu) and long interspersed nucleotide element­1 (Line­1). This was accompanied by an increase in the expression of PDGF, and reductions of p53, PTEN and MFN2, both in mRNA and protein levels. An elevation of S­adenosylmethionine (SAM) and a reduction of S­adenosylhomocysteine (SAH) and the SAM/SAH ratio were also identified. In conclusion, Hcy impacted methylation the of AS­associated genes and global methylation status that mediate the cell proliferation, which may be a character of VSMCs treated with Hcy. The data provided evidence for mechanisms of VSMCs proliferation in AS induced by Hcy and may provide a new perspective for AS induced by Hcy.


Subject(s)
DNA Methylation/drug effects , Epigenesis, Genetic , Homocysteine/pharmacology , Myocytes, Smooth Muscle/drug effects , Promoter Regions, Genetic , Alu Elements , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , Cell Proliferation/drug effects , CpG Islands , Female , GTP Phosphohydrolases/genetics , GTP Phosphohydrolases/metabolism , Humans , Long Interspersed Nucleotide Elements , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Models, Biological , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/metabolism , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Platelet-Derived Growth Factor/genetics , Platelet-Derived Growth Factor/metabolism , Primary Cell Culture , S-Adenosylhomocysteine/metabolism , S-Adenosylmethionine/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Umbilical Veins/cytology , Umbilical Veins/drug effects , Umbilical Veins/metabolism
7.
Oncol Lett ; 14(6): 8000-8006, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29344242

ABSTRACT

Oxysophoridine (OSR) is a major active alkaloid extracted from Sophoraalopecuroides L. The aim of the present study was to investigate the induction of the apoptotic effects of OSR on colorectal cancer cells in vivo and in vitro. The results of the MTT and colony formation assays demonstrated that the proliferation of HCT116 cells was inhibited by OSR in vitro. The characteristics of cellular apoptosis in OSR-treated HCT116 cells were analyzed by Hoechst 33258 staining. It was also observed that the expression of caspase-3, B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) and cytochrome c increased significantly upon OSR treatment. However, the expression of Bcl-2 and poly ADP-ribose polymerase-1 (PARP-1) was downregulated in OSR-treated cells compared with untreated cells. The in vivo experiments identified that OSR significantly inhibited the growth of the transplanted mouse CT26 tumor tissue, upregulated the expression of caspase-3, Bax and cytochrome c and downregulated the expression of Bcl-2 and PARP-1, as detected by reverse transcription-quantitative polymerase chain reaction and western blotting. It may be concluded that OSR significantly induced apoptotic effects on colorectal cancer cells in vivo and in vitro, and that its mechanism may be associated with the Bcl-2/Bax/caspase-3 signaling pathway.

8.
PLoS One ; 11(10): e0162821, 2016.
Article in English | MEDLINE | ID: mdl-27760157

ABSTRACT

Both tyrosine kinase and topoisomerase II (TopII) are important anticancer targets, and their respective inhibitors are widely used in cancer therapy. However, some combinations of anticancer drugs could exhibit mutually antagonistic actions and drug resistance, which further limit their therapeutic efficacy. Here, we report that HMNE3, a novel bis-fluoroquinolone chalcone-like derivative that targets both tyrosine kinase and TopII, induces tumor cell proliferation and growth inhibition. The viabilities of 6 different cancer cell lines treated with a range of HMNE3 doses were detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was determined using Hoechst 33258 fluorescence staining and the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay. The expression of activated Caspase-3 was examined by immunocytochemistry. The tyrosine kinase activity was measured with a human receptor tyrosine kinase (RTK) detection kit using a horseradish peroxidase (HRP)-conjugated phosphotyrosine (pY20) antibody as the substrate. The topoisomerase II activity was measured using agarose gel electrophoresis with the DNA plasmid pBR322 as the substrate. The expression levels of the P53, Bax, Bcl-2, Caspase-3, -8, -9, p-cSrc, c-Src and topoisomerase II proteins were detected by western blot analysis. The proliferation of five of the six cancer cell lines was significantly inhibited by HMNE3 at 0.312 to 10 µmol/L in a time- and dose-dependent manner. Treatment of the Capan-1 and Panc-1 cells with 1.6 to 3.2 µM HMNE3 for 48 h significantly increased the percentage of apoptotic cells (P<0.05), and this effect was accompanied by a decrease in tyrosine kinase activity. HMNE3 potentially inhibited tyrosine kinase activity in vitro with an IC50 value of 0.64±0.34 µmol/L in Capan-1 cells and 3.1±0.86 µmol/L in Panc-1 cells. The activity of c-Src was significantly inhibited by HMNE3 in a dose- and time-dependent manner in different cellular contexts. Compared with the control group, HMNE3 induced increased expression of cellular apoptosis-related proteins. Consistent with cellular apoptosis data, a significant decrease in topoisomerase IIß activity was noted following treatment with HMNE3 for 24 h. Our data suggest that HMNE3 induced apoptosis in Capan-1 and Panc-1 cells by inhibiting the activity of both tyrosine kinases and topoisomerase II.


Subject(s)
Chalcone/chemistry , Ciprofloxacin/analogs & derivatives , DNA Topoisomerases, Type II/metabolism , Pancreatic Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Topoisomerase II Inhibitors/pharmacology , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Ciprofloxacin/chemistry , Humans
9.
Can J Physiol Pharmacol ; 94(7): 769-78, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27175624

ABSTRACT

Gentiopicroside (Gent) is promising as an important protective secoiridoid compound against pain. The present study was designed to investigate whether administration of Gent would alleviate the expression of nociceptive behaviors and whether it would cause the relevant electrophysiological changes in a chronic constriction injury (CCI) model of neuropathic pain in mice. Gent was administered from the seventh day after surgery for 8 consecutive days. Behavioral parameters and sciatic functional index were assessed immediately before surgery and on days 7, 8, 10, 12, and 14 post-CCI, and electrophysiological activities of sciatic nerve were recorded immediately after the behavioral test on the last day. The present study has shown that administration of Gent (at a dose of 50 and 100 mg/kg) increased behavioral parameters from day 8 compared with the CCI-NS group. Electrophysiological data indicated that CCI caused a significant reduction in nerve conduction velocities in the sciatic nerves and the amplitudes of compound action potential, while Gent at a dose of 50 or 100 mg/kg caused a significant recovery of electrophysiological changes induced by CCI. Our data indicated that Gent has antinociceptive effects on neuropathic pain induced by CCI.


Subject(s)
Analgesics/therapeutic use , Electrophysiological Phenomena/drug effects , Iridoid Glucosides/therapeutic use , Locomotion/drug effects , Neuralgia/drug therapy , Sciatic Neuropathy/drug therapy , Analgesics/pharmacology , Animals , Constriction , Dose-Response Relationship, Drug , Electrophysiological Phenomena/physiology , Iridoid Glucosides/pharmacology , Locomotion/physiology , Male , Mice , Mice, Inbred ICR , Neuralgia/physiopathology , Sciatic Neuropathy/physiopathology
10.
Int J Clin Exp Pathol ; 8(7): 7937-44, 2015.
Article in English | MEDLINE | ID: mdl-26339359

ABSTRACT

The purpose of this article is to research on whether MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma (BUC). In this study, the expression of MACC1 gene was knocked down by RNA interference (RNAi) in the T24 cell (human BUC cell). The transcription level of MACC1 was detected by RT-PCR. Activities of MACC1, caspase-3, caspase-8, Bax and Met (mesenchymal-epithelial transition factor) protein were measured by Western blot. The cell proliferation and apoptosis were detected by MTT and flow cytometry. The cell's invasion ability was performed on Matrigel transwell assay. We also detect MMP2 (metalloproteinase-2) proteins by ELISA. The results showed that the level of MACC1 mRNA and protein was significantly reduced after RNAi. MTT assay showed that the proliferation of T24 cell was decreased due to RNA interference. Apoptosis studies also showed that MACC1 gene interference in T24 loses its anti-apoptotic effects. The expression of apoptosis proteins (Caspase-3, Caspase-8 and Bax) increased significantly due to the MACC1 RNAi. The level of Met protein was down-regulated obviously due to RNAi. Transwell assay showed that invasion abilities of T24 cells were reduced obviously due to MACC1 RNAi. Further studies showed that the secretion of MMP-2 was reduced by RNAi. It can conclude that the ability of proliferation and invasion in T24 cells can be inhibited by RNAi-targeting MACC1. As a result, MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma.


Subject(s)
Carcinoma/genetics , Cell Movement , Cell Proliferation , RNA Interference , Transcription Factors/genetics , Urinary Bladder Neoplasms/genetics , Apoptosis , Carcinoma/metabolism , Carcinoma/pathology , Caspase 3/genetics , Caspase 3/metabolism , Caspase 8/genetics , Caspase 8/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , Matrix Metalloproteinase 2/metabolism , Neoplasm Invasiveness , Proto-Oncogene Proteins c-met/genetics , Proto-Oncogene Proteins c-met/metabolism , RNA, Messenger/metabolism , Signal Transduction , Time Factors , Trans-Activators , Transcription Factors/metabolism , Transfection , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism
11.
Planta Med ; 81(10): 791-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26132856

ABSTRACT

Oxysophocarpine is an alkaloid extracted from Sophora alopecuroides. We investigated the analgesic effect of oxysophocarpine on carrageenan-induced inflammatory pain in mice, in order to explore its possible mechanisms. Mouse ear swelling tests and carrageenan-induced paw edema tests were used to investigate the effects of oxysophocarpine on inflammatory pain in mice. Morphological changes on inflamed paw sections were measured by hematoxylin-eosin staining. The mRNA and protein expression of extracellular signal-regulated kinase, phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, tumor necrosis factor α, interleukin-1 beta, interleukin-6 and prostaglandin E2 were investigated by real-time quantitative polymerase chain reaction, immunohistochemistry, western-blot and enzyme-linked immunosorbent assay. In our results, oxysophocarpine shows a significant anti-inflammatory effect in the mouse ear swelling test. Oxysophocarpine also significantly reduced the paw edema volume and improved mechanical allodynia threshold value on carrageenan-induced inflammatory pain, as well as relieved paw tissues inflammatory damage and reduced the numbers of neutrophils in mice. Oxysophocarpine significantly suppressed over-expression of cyclooxygenase-2, tumor necrosis factor α, interleukin-1 beta, interleukin-6 and prostaglandin E2, and inhibited the over-phosphorylation of extracellular signal-regulated kinase 1/2. Based on these findings we propose that oxysophocarpine attenuates inflammatory pain by suppressing the levels of phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, prostaglandin E2, tumor necrosis factor α, interleukin-1 beta and interleukin-6.


Subject(s)
Alkaloids/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Dinoprostone/metabolism , Inflammation/drug therapy , Pain/drug therapy , Animals , Carrageenan/toxicity , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Cytokines/genetics , Cytokines/metabolism , Dinoprostone/antagonists & inhibitors , Edema/chemically induced , Edema/drug therapy , Gene Expression Regulation/drug effects , Inflammation/chemically induced , Inflammation/metabolism , Interleukin-1beta/metabolism , Mice , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/metabolism , Pain/chemically induced
12.
J Nat Med ; 69(4): 575-83, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26142710

ABSTRACT

Aloperine (ALO), one of the alkaloids isolated from Sophora alopecuroides L., is traditionally used for various diseases including neuronal disorders. This study investigated the protective effects of ALO on neonatal rat primary-cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion (OGD/RP). Treatment with ALO (25, 50, and 100 mg/l) attenuated neuronal damage (p < 0.01), with evidence of increased cell viability (p < 0.01) and decreased cell morphologic impairment. Furthermore, ALO increased mitochondrial membrane potential (p < 0.01), but inhibited intracellular-free calcium [Ca(2+)] i (p  < 0.01) elevation in a dose-dependent manner at OGD/RP. ALO also reduced the intracellular reactive oxygen species and malondialdehyde production and enhanced the antioxidant enzymatic activities of catalase, superoxide dismutase, glutathione peroxidase and the total antioxidant capacity. The results suggested that ALO has significant neuroprotective effects that can be attributed to anti-oxidative stress.


Subject(s)
Hippocampus/drug effects , Neurons/drug effects , Piperidines/therapeutic use , Reperfusion Injury/metabolism , Animals , Apoptosis , Glucose/metabolism , Neuroprotective Agents/pharmacology , Oxygen , Piperidines/administration & dosage , Quinolizidines , Rats , Rats, Sprague-Dawley
14.
Biochem Biophys Res Commun ; 451(4): 568-73, 2014 Sep 05.
Article in English | MEDLINE | ID: mdl-25128276

ABSTRACT

OBJECTIVE: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. METHODS: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in the spinal cord (L4/5) were analyzed by using Western blot. RESULTS: Administration of ALO (80mg/kg and 40mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1ß at the dose of 80mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10mg/kg (i.p.). CONCLUSION: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.


Subject(s)
Hyperalgesia/drug therapy , NF-kappa B/antagonists & inhibitors , Neuralgia/drug therapy , Piperidines/pharmacology , Animals , Antioxidants/pharmacology , Constriction , Down-Regulation , Hot Temperature , Interleukin-1beta/biosynthesis , Interleukin-6/biosynthesis , Male , Mice , Quinolizidines , Sciatic Nerve/injuries , Tumor Necrosis Factor-alpha/biosynthesis
15.
Pharm Biol ; 52(8): 1052-9, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24601951

ABSTRACT

CONTEXT: Oxysophocarpine (OSC), a quinolizidine alkaloid extracted from leguminous plants of the genus Robinia, is traditionally used for various diseases including neuronal disorders. OBJECTIVE: This study investigated the protective effects of OSC on neonatal rat primary-cultured hippocampal neurons were injured by oxygen-glucose deprivation and reperfusion (OGD/RP). MATERIALS AND METHODS: Cultured hippocampal neurons were exposed to OGD for 2 h followed by a 24 h RP. OSC (1, 2, and 5 µmol/L) and nimodipine (Nim) (12 µmol/L) were added to the culture after OGD but before RP. The cultures of the control group were not exposed to OGD/RP. MTT and LDH assay were used to evaluate the protective effects of OSC. The concentration of intracellular-free calcium [Ca(2+)]i and mitochondrial membrane potential (MMP) were determined to evaluate the degree of neuronal damage. Morphologic changes of neurons following OGD/RP were observed with a microscope. The expression of caspase-3 and caspase-12 mRNA was examined by real-time quantitative PCR. RESULTS: The IC50 of OSC was found to be 100 µmol/L. Treatment with OSC (1, 2, and 5 µmol/L) attenuated neuronal damage (p < 0.001), with evidence of increased cell viability (p < 0.001) and decreased cell morphologic impairment. Furthermore, OSC increased MMP (p < 0.001), but it inhibited [Ca(2+)]i (p < 0.001) elevation in a dose-dependent manner at OGD/RP. OSC (5 µmol/L) also decreased the expression of caspase-3 (p < 0.05) and caspase-12 (p < 0.05). DISCUSSION AND CONCLUSION: The results suggested that OSC has significant neuroprotective effects that can be attributed to inhibiting endoplasmic reticulum (ER) stress-induced apoptosis.


Subject(s)
Alkaloids/pharmacology , Glucose/metabolism , Hippocampus/drug effects , Neurons/drug effects , Neuroprotective Agents/pharmacology , Oxygen/metabolism , Animals , Animals, Newborn , Cell Hypoxia/drug effects , Cell Hypoxia/physiology , Cells, Cultured , Hippocampus/cytology , Hippocampus/metabolism , Neurons/cytology , Neurons/metabolism , Rats , Rats, Sprague-Dawley , Reperfusion Injury , Treatment Outcome
16.
Neurochem Res ; 38(11): 2408-17, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24078262

ABSTRACT

Our previous studies have demonstrated that oxysophoridine (OSR) has protective effects on cerebral neurons damage in vitro induced by oxygen and glucose deprivation. In this study, we further investigated whether OSR could reduce ischemic cerebral injury in vivo and its possible mechanism. Male Institute of cancer research mice were intraperitoneally injected with OSR (62.5, 125 and 250 mg/kg) for seven successive days, then subjected to brain ischemia induced by the model of middle cerebral artery occlusion. After reperfusion, neurological scores and infarct volume were estimated. Morphological examination of tissues was performed. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining. Oxidative stress levels were assessed by measurement of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. The expression of various apoptotic markers as Caspase-3, Bax and Bcl-2 were investigated by immunohistochemistry and Western-blot analysis. OSR pretreatment groups significantly reduced infract volume and neurological deficit scores. OSR decreased the percentage of apoptotic neurons, relieved neuronal morphological damage. Moreover, OSR markedly decreased MDA content, and increased SOD, GSH-Px activities. Administration of OSR (250 mg/kg) significantly suppressed overexpression of Caspase-3 and Bax, and increased Bcl-2 expression. These findings indicate that OSR has a protective effect on focal cerebral ischemic injury through antioxidant and anti-apoptotic mechanisms.


Subject(s)
Alkaloids/pharmacology , Brain Ischemia/prevention & control , Reperfusion Injury/prevention & control , Animals , Apoptosis/drug effects , Infarction, Middle Cerebral Artery/metabolism , Male , Mice , Mice, Inbred ICR , Oxidative Stress/drug effects
17.
Mol Med Rep ; 8(4): 1251-5, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23939784

ABSTRACT

Escherichia coli is a common cause of community­ and hospital­acquired urinary tract infections, and class 1 integrons are the prior elements of gene transference in the capture and distribution of gene cassettes among clinical gram-negative bacillus. In the present study, the resistance of Escherichia coli to antimicrobial agents was investigated. A total of 97 isolates were found to be susceptible to 16 antimicrobial agents and were detected in the production of extended ß­lactamases (ESBLs), distribution of CTX­M­type ß­lactamases, presence and characterization of class 1 integrons and a variable region of integron­positive isolates. Escherichia coli isolates possessing CTX­M (31; 32%) were detected in 19 isolates (61.5%). The presence of ESBLs was associated with resistance to penicillins, third-generation cephalosporins, ciprofloxacin, aminoglycosides and monocyclic ß­lactam antibiotics. Escherichia coli isolates (69; 71.1%) possessed class 1 integrons associated with resistance to ciprofloxacin and numerous third-generation cephalosporins, penicillins, tobramycin and trimethoprim­sulfamethoxazole. The four gene cassette arrangements were as follows: dfrA17­aadA5, aadA1, aacC4­cmlA1 and dfr2d, and 8 carried two disparate class 1 integrons. Five isolates presented class 1 integrons containing no gene cassettes. The distribution of ESBLs and class 1 integrons in Escherichia coli were prevalent with drug resistance in Chengdu. In addition, the resistance range of Escherichia coli isolates that harboured ESBLs and carried class 1 integrons were similar. The current study demonstrated the presence of class 1 integrons and ESBLs, which jointly mediate the resistance of Escherichia coli isolates to a number of antibacterial agents.


Subject(s)
Anti-Bacterial Agents/pharmacology , Escherichia coli Proteins/genetics , Escherichia coli/genetics , Integrons , beta-Lactamases/genetics , Disk Diffusion Antimicrobial Tests , Escherichia coli/drug effects , Escherichia coli/enzymology , Escherichia coli Proteins/metabolism , Humans , beta-Lactam Resistance/genetics , beta-Lactamases/metabolism
18.
Exp Biol Med (Maywood) ; 234(8): 908-17, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19546357

ABSTRACT

Lanthanum, a rare earth element, has been used to decrease serum phosphorus level in patients with chronic renal disease and hyperphosphatemia. We aimed to observe the effect and mechanism of two doses of lanthanum acetate (375 and 750 mg/kg/day) on vascular calcification induced by vitamin D3 plus nicotine treatment in rats for 4 weeks. As compared with control rats, rats with calcification showed widespread calcified nodules and irregular elastic fibers in calcified aorta on von Kossa calcium staining and increased aortic calcium and phosphorus contents, alkaline phosphatase (ALP) activity and bone-related protein expressions for osteopontin (OPN) and type III sodium dependent phosphate cotransporter Pit-1 (Pit-1). After treatment with either dose of lanthanum acetate, the calcified nodules and degree of irregular elastic fibers decreased in aortas. Lanthanum acetate at 750 mg/kg/day was more effective than 375 mg/kg/day in lessening vascular calcification by significantly reducing plasma phosphorus level, calcium x phosphorus product and ALP activity, by 30.3%, 28.6%, and 68.6%, respectively; reducing aortic phosphorus and calcium contents and ALP activity, by 48%, 53.1%, and 63.5% (all P < 0.01), respectively; reducing aortic mRNA level of OPN and Pit-1, by 55.8% (P < 0.01) and 38.8% (P < 0.05) and protein level of OPN and Pit-1, by 37.2% and 27.2% (both P < 0.01), respectively; and increasing carboxylated matrix Gla-protein (MGP) protein expression by 33.7% (P < 0.05), as compared with rats treated with vitamin D3 and nicotine alone. Lanthanum acetate could effectively inhibit the pathogenesis of vascular calcification.


Subject(s)
Acetates/pharmacology , Aorta/drug effects , Aorta/pathology , Calcinosis/chemically induced , Calcinosis/prevention & control , Cholecalciferol/pharmacology , Lanthanum/pharmacology , Nicotine/adverse effects , Acetates/blood , Animals , Aorta/metabolism , Calcinosis/blood , Calcium/blood , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Gene Expression Regulation/drug effects , Lanthanum/blood , Male , Osteopontin/genetics , Osteopontin/metabolism , Phosphorus/blood , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Sodium-Phosphate Cotransporter Proteins, Type III/genetics , Sodium-Phosphate Cotransporter Proteins, Type III/metabolism , Matrix Gla Protein
19.
Zhongguo Zhong Yao Za Zhi ; 33(7): 822-4, 2008 Apr.
Article in Chinese | MEDLINE | ID: mdl-18589792

ABSTRACT

OBJECTIVE: To study the analgesic effects and sites of oxymatrine-carbenoxolone sodium complex (OCSC). METHOD: Adopting formalin test, warm water tail-flick test and intracerebroventricularly (icv) injection to observe the analgesic effects of OCSC in mice. RESULT: Intraperitoneally injecting (ip) OCSC (75, 150 mg x kg(-1)) remarkedly inhibited the pain of mice in the formalin test and prolonged latent phases of tail-shrinking of mice, icy OCSC (1.875, 3.75, 7.5 mg x kg(-1)) significantly prolonged latent phases of tail-shrinking of mice, it had dose-dependent effect with concentration. CONCLUSION: The result indicated that OCSC has obvious analgesic effects and its mechanism may be involved in central nervous system (CNS).


Subject(s)
Alkaloids/chemistry , Analgesics/chemistry , Analgesics/pharmacology , Carbenoxolone/chemistry , Carbenoxolone/pharmacology , Quinolizines/chemistry , Analgesics/administration & dosage , Analgesics/therapeutic use , Animals , Carbenoxolone/administration & dosage , Carbenoxolone/therapeutic use , Dose-Response Relationship, Drug , Female , Male , Mice , Mice, Inbred ICR , Pain/drug therapy
20.
Peptides ; 28(4): 900-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17306419

ABSTRACT

In this work we aimed to observe (1) the changes in adrenomedullin (AM) and its receptor system - calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMPs) - in myocardial ischemic injury and (2) the response of injuried myocardia to AM and the phosphorylation of Akt to illustrate the protective mechanism of AM in ischemic myocardia. Male SD rats were subcutaneously injected with isoproterenol (ISO) to induce myocardial ischemia. The mRNA levels of AM, CRLR, RAMP1, RAMP2 and RAMP3 were determined by RT-PCR. Protein levels of Akt, phosphor-Akt, CRLR, RAMP1, RAMP2 and RAMP3 were assayed by Western blot. Results showed that, compared with that of the controls, ISO-treated rats showed lower cardiac function and myocardial injury. The mRNA relative amount of AM, CRLR, RAMP1, RAMP2 and RAMP3 in the myocardia of ISO-treated rats was increased. The elevated mRNA levels of CRLR, RAMP1, RAMP2 and RAMP3 were positively correlated with AM content in injured myocardia. The protein levels of CRLR, RAMP1, RAMP2 and RAMP3 in injured myocardia were increased compared with that of control myocardia. AM-stimulated cAMP generation in myocardia was elevated in the ISO group, and was antagonized by AM(22-52) and CGRP(8-37). Western blot analyses revealed that AM significantly enhanced Akt phosphorylation in injured myocardia, which was blocked by pretreatment with AM(22-52) or CGRP(8-37). Ischemia-injured myocardia hyper-expressed AM and its receptors - CRLR, RAMP1, RAMP2 and RAMP3 - and the response of ischemic myocardia to AM was potentiated, and the level of Akt phosphorylation was also increased, which suggests that changes in cardiac AM/AM receptor might play an important role in the pathogenesis of myocardial ischemic injury.


Subject(s)
Adrenomedullin/pharmacology , Cyclic AMP/metabolism , Heart/drug effects , Myocardium/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Blotting, Western , Calcitonin Receptor-Like Protein , Cardiotonic Agents/pharmacology , Disease Models, Animal , Gene Expression Regulation/drug effects , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Isoproterenol/toxicity , Lipid Peroxides/metabolism , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Myocardial Ischemia/chemically induced , Myocardial Ischemia/genetics , Myocardial Ischemia/metabolism , Natriuretic Peptide, Brain , Nerve Tissue Proteins/genetics , Phosphorylation/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Radioimmunoassay , Rats , Rats, Sprague-Dawley , Receptor Activity-Modifying Proteins , Receptors, Calcitonin/genetics , Receptors, Calcitonin/metabolism , Reverse Transcriptase Polymerase Chain Reaction
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