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AIM: To study the effect and mechanism of Delicaflavone on migration and invasion of gefitinib-resistant lung cancer cell line PC-9/GR. METHODS: MTT assay was used to detect cell viability. Transwell and scratch assays were used to detect cell invasion and migration abilities. Western blotting was used to detect the expressions of MMP-9, MMP-2, E-cadherin, N-cadherin, Vimentin and PI3K/Akt/mTOR pathway-related proteins in PC-9/GR cells. RESULTS: Compared with control group, 20 mg/L Delicaflavone could significantly inhibit the viability of PC-9/GR cells for 24 h (P<0.05), while Delicaflavone below 10 mg/L had no significant effect on cell proliferation. The number of invasive cells and migrated cells were decreased significantly by Delicaflavone in a concentration-dependent way (P<0.05 and P<0.01). Delicaflavone could concentration-dependently reduce the expression of MMP-9, MMP-2, N-cadherin, vimentin (P<0.01), meanwhile up-regulate the expression of E-cadherin (P<0.01). In addition, Delicaflavone also decreased the expression of p-PI3K, p-Akt and p-mTOR in a concentration-dependent manner (P<0.01). CONCLUSION: Delicaflavone can inhibit the migration and invasion of PC-9/GR cells by regulating epithelial-mesenchymal transition via PI3K/Akt/mTOR pathway.
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Objective:To explore the long-term influence of donor central graft thickness (CGT) and donor graft size on corneal endothelial cell density (ECD) after Descemet stripping automated endothelial keratoplasty (DSAEK).Methods:An observational case series study was conducted.One hundred and forty-four eyes of 134 patients who underwent DSAEK in Peking University Third Hospital from January 2013 to December 2017 with at least 24-month follow-up were enrolled.Preoperative donor ECD was evaluated by specular microscopy, and ECD was determined by in vivo confocal microscopy at 1, 3, 6, 12, and 24 months postoperatively.Donor CGT was measured by anterior segment optical coherence tomography.According to the 3-month postoperative donor CGT, the subjects were divided into thinner graft group (45 eyes with CGT<100 μm), medium-thick graft group (66 eyes with CGT≥100-<150 μm) and thicker graft group (33 eyes with CGT≥150 μm). According to the donor trephination size, the subjects were divided into smaller graft group (31 eyes with trephination size≥7-<8 mm) and larger graft group (113 eyes with trephination size≥8-<9 mm). The changes of the donor CGT and corneal endothelial cell loss rate were compared at different time points after surgery.The relationships between 24-month postoperative ECD and donor ECD, donor graft size and donor CGT were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University Third Hospital (No.IRB00006761-2008025). Written informed consent was obtained from each subject prior to any medical examination. Results:The donor CGT was 129.0 (90.8, 160.8), 115.5 (93.0, 146.0), 115.5 (89.0, 151.0), 112.5 (94.3, 146.8) and 114.0 (89.0, 144.5) μm at 1, 3, 6, 12 and 24 months after surgery, showing a statistically significant difference ( H=37.369, P<0.001). There was a statistically significant difference between 1-month and 3-month postoperative CGT ( P<0.001). There was no statistically significant difference in the endothelial cell loss rate among the three different donor CGT groups and between the two different donor graft size groups at any postoperative time points (all at P>0.05). Spearman correlation analysis showed that the 24-month postoperative ECD was strongly positively correlated with the preoperative donor ECD( rs=0.783, P<0.001), which was not associated with donor graft size and donor CGT ( rs=0.141, P=0.093; rs=-0.044, P=0.600). Conclusions:Larger postoperative ECD is correlated with larger preoperative ECD of donor graft.Lower long-term corneal endothelial cell loss rate after DSAEK is associated with thinner and larger diameter of donor graft.
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OBJECTIVE@#To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism.@*METHODS@#A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR.@*RESULTS@#Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.
Subject(s)
Animals , Rats , Acupuncture Points , Depression/therapy , Hippocampus/metabolism , Hydrocortisone/metabolism , Hypothyroidism/therapy , Moxibustion , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Receptors, Glucocorticoid/metabolism , Receptors, Mineralocorticoid/metabolism , Serotonin , Thyrotropin/metabolism , Triticum/metabolismABSTRACT
Clinical phenotype and gene characteristics of a patient diagnosed with Imerslund-Gr?sbeck syndrome (IGS) in Department of Neurology, Children′s Hospital of Soochow University in December 2018 were analyzed retrospectively, and literature review was conducted.The 16 years and 5 months old boy was admitted to the hospital with symptoms of weakness of lower limbs for 2 weeks.He had a history of megaloblastic anemia and isolated proteinuria.Genetic metabolism of hematuria showed methylmalonic academia.Genetic analysis revealed a compound heterozygous AMN gene mutation[c.742C>T(p.Q248 *) and c. 761G>A(p.G254E)]. These two mutations were derived from his parents respectively, which had been reported before.Symptoms of the patient improved after intramuscular administration of hydroxycobalamin and oral betaine.Review of the literature indicated that the clinical manifestations of AMN gene-related IGS were mostly megaloblastic anemia and isolated proteinuria, and the older children might suffer from neurological symptoms such as movement disorders, dementia, delirium or psychosis.The clinical phenotype of this disease was variable, which might easily lead to misdiagnosis.The patient presented with a special phenotype of mild reversible peripheral neuropathy, which expanded the clinical phenotype of pathogenic genes of AMN gene.In addition, peripheral neuropathy caused by vitamin B 12 metabolic disorders is reversible, and it is suggested to measure vitamin B 12, test related genes and treatment with vitamin B 12 in peripheral neuropathy of unknown etiology.
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Objective:To observe the effect of Sinisan on the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrKB), 5-hydroxytryptamine (5-HT)/5-HT1A receptor (5-HT1AR), and hypothalamus-pituitary-adrenal (HPA) axis in depressed rats, and explore the antidepressant mechanism of Sinisan based on BDNF/TrKB, 5-HT/5-HT1AR, and HPA axis. Method:A total of 120 male Wistar rats were randomly divided into a normal group, a model group, a fluoxetine (0.01 g·kg<sup>-1</sup>) group, and low- (1.25 g·kg<sup>-1</sup>), medium- (2.5 g·kg<sup>-1</sup>), and high-dose (5 g·kg<sup>-1</sup>) Sinisan groups, with 20 rats in each group. The depression model was induced by isolation combined with chronic unpredictable mild stimulation(CUMS) in rats except for those in the normal group for 21 days. Rats were then treated correspondingly once a day for 21 days by gavage. Those in the normal group and the model group received an equal volume of normal saline. During the intervention, the model rats were stimulated continuously. The depressive state of CUMS model rats was evaluated by sucrose preference test and open field test. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in the plasma and BDNF and 5-HT levels in the hippocampal homogenate. The mRNA expression of hippocampal TrKB, 5-HT1AR, glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) was detected by real-time fluorescence-based quantitative polymerase chain reaction (Real-time PCR). The protein expression of hippocampal TrKB, 5-HT1AR, GR, and MR was detected by Western blot. The histomorphological changes of the hippocampus were observed by hematoxylin-eosin (HE) staining. Result:Compared with the normal group, the model group showed decreased sucrose preference rate (<italic>P</italic><0.01), reduced horizontal and vertical scores in the open field test (<italic>P</italic><0.01), increased plasma content of CRH, ACTH, and CORT (<italic>P</italic><0.01), declining content of BDNF and 5-HT in the hippocampus (<italic>P</italic><0.01), dwindled mRNA and protein expression levels of TrKB, 5-HT1AR, and GR (<italic>P</italic><0.01), elevated mRNA and protein expression of MR (<italic>P</italic><0.01), and damaged hippocampal neurons revealed by HE staining. Compared with the model group, the groups with drug intervention showed increased sucrose preference rate (<italic>P</italic><0.01) and horizontal and vertical scores in the open field test (<italic>P</italic><0.05, <italic>P</italic><0.01), decreased content of plasma CRH, ACTH, and CORT (<italic>P</italic><0.05, <italic>P</italic><0.01), elevated content of hippocampal BDNF and 5-HT (<italic>P</italic><0.05, <italic>P</italic><0.01), elevated mRNA and protein expression levels of hippocampal TrKB, 5-HT1AR, and GR (<italic>P</italic><0.05, <italic>P</italic><0.01), reduced mRNA and protein expression levels of hippocampal MR (<italic>P</italic><0.05, <italic>P</italic><0.01), and recovered hippocampal neurons as revealed by HE staining. Conclusion:Sinisan can exert a significant antidepressant effect by increasing hippocampal BDNF and 5-HT content, up-regulating TrKB, 5-HT1AR, and GR mRNA and protein expression, down-regulating MR mRNA and protein expression, inhibiting HPA axis hypertrophy, and enhancing the regeneration and repair of hippocampal neurons.
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The anti-inflammatory activity and compatibility ratio of flavonoids in Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle(GR) and Angelicae Sinensis Radix(AS) were evaluated by the superoxide anion scavenging test. The matrix formula of gel was optimized by orthogonal test design and the model of deep partial-thickness scald in mice was induced. The gel was applied to the wound. The tissue water content, wound healing rate, serum TNF-α and IL-1, and EGF and VEGF in tissues were measured at diffe-rent periods. The results revealed that when the compatibility ratio of GR and AS was 1∶2, the maximal scavenging efficacy on supe-roxide anion was observed. The gel displayed the optimal properties when carbomer(1%), glycerol(5%), propylene glycol(10%) were added into the matrix. Gel external application can significantly improve the wound healing rate, relieve tissue edema, diminish tissue water content, alleviate inflammatory reaction, and increase the content of EGF and VEGF in tissues(P<0.05). The gel prepared in the present study is effective in promoting granulation, relieving pain, resisting inflammation, and alleviating edema, and is potent in healing scalds.
Subject(s)
Animals , Mice , Anti-Inflammatory Agents , Drugs, Chinese Herbal , Flavonoids , Glycyrrhiza , RhizomeABSTRACT
@#[Abstract] Objective:ToinvestigatetheroleofmiR-125a-5pininducingthegefitinib(Gef)-resistance of non-small cell lung carcinoma (NSCLC) cells and its possible mechanism. Methods: Human NSCLC drug-resistant cell line A549/GR and NSCLC cell line A549 were chosen for this study. miR-125a-5p mimic, miR-125a-5p inhibitor, pcDNA3.1-APAF1 and empty vector pcDNA3.1 were transfected into A549/GR cells. The expression level of miR-125a-5p in cell lines was detected by qPCR. MTT, Transwell and Flow cytometry were used to detect the effects of Gef on proliferation, migration and apoptosis of cell lines, respectively. The targeting relationship between miR-125a-5p and APAF1 (apoptotic peptidase activating factor 1) was verified by Dual-luciferase reporter gene system. In addition, the expression of APAF1 protein in A549/GR cells was detected by Western blotting. The expression levels of caspase-3 and caspase-9 were assessed by colorimetry. Results: Expression level of miR-125a-5p was upregulated significantly in Gefresistant A549/GR cells (P<0.01). AndtheinfluencesofGefonA549/GRcellswereenhancedby knockdown of miR-125a-5p, including inhibiting cell proliferation and migration (all P<0.05) and inducing apoptosis (P<0.01). Dual luciferase reporter gene assay confirmed that miR-125a-5p targeted APAF1 and negatively regulated its expression. Furthermore, by targetedly downregulating APAF1, miR-125a-5p alleviated the inhibition of proliferation and migration (all P<0.05) and promotion of apoptosis (P<0.05) of A549/GR cells caused by Gef, and attenuated Gef-induced upregulation of apoptosis-related proteins caspase-3 and caspase-9 (all P<0.05). Conclusion: miR-125a-5p promotes Gef-resistance of A549/GR cells, and the underlying mechanisms are promotion of proliferation, migration and inhibition of apoptosis of non-small cell lung cancer cells by targetingAPAF1.
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Objective By establishing the intervention mode of 12-week gait retraining (GR) (with the specific aim of changing the habitual running gait), to determine the changes of vertical ground reaction force (vGRF), kinematics and dynamics of hip, knee, ankle joints, as well as stiffness of lower limbs in running before and after GR, and to explore the influence of running posture transformation on impact force and lower limb biomechanics. Methods Vicon motion capture system and Kistler 3D force measurement platform were used to collect the GRF and marker track of 30 runners (15 in experimental group and 15 in control group) before and after GR with the minimalist shoes at a speed of 12 km/h±5%. Results A total of 17 subjects (9 in experimental group and 8 in control group) completed the GR. After GR, the maximum loading rate of both groups decreased significantly, and the maximum loading rate of experimental group was lower than that of control group. The foot strike angle in experimental group decreased significantly after GR, and the plantarflexion angle and hip joint angular extension velocity increased in both groups. The force moment of ankle joint increased in experimental group, and the stiffness of lower limbs was significantly improved in both groups. Conclusions A 12-week GR exercise intervention model was successfully established, with 78% conversion rate (from rearfoot strike to forefoot strike). GR can effectively avoid the peak of impact force, reduce the maximum loading rate, increase the lower limb stiffness, and thus reduce or even avoid the risk of running injury caused by impact force and may provide a possibility for the improvement of running economy.
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Terpenoids are main bioactive components in Tripterygium wilfordii,but the contents of some terpenoids are relatively low. In order to provide scientific evidence for the regulation of terpenoids in T. wilfordii,this research explored the effect of GR24 on accumulations of four diterpenoids( triptolide,tripterifordin,triptophenolide,and triptinin B) in T. wilfordii suspension cells by biological technology and UPLC-QQQ-MS/MS. The results indicated that 100 μmol·L-1 GR24 inhibited the accumulations of triptolide,tripterifordin,triptophenolide,and triptinin B to different degrees. Compared with the control group,the contents of 4 diterpenoids( in the induced group) were down to 96.59%,63.80%,61.02% and 33.59% in 240 h,respectively. Among them,the accumulation of triptinin B iswas significantly inhibited. In addition,the key time point of inhibitory effect was 120 h after induction with GR24 in some diterpenoids. This is the first systematic study focusing on the effect of GR24 on the accumulations of diterpenoids in T. wilfordii suspension cells. The dynamic accumulation ruleregularity of four diterpenoids after induced by GR24 was summarized,which laid a foundation for further study on the chemical response mechanism of terpenoids to GR24.
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Humans , Cells, Cultured , Diterpenes , Pharmacokinetics , Lactones , Pharmacology , Tandem Mass Spectrometry , Terpenes , Tripterygium , ChemistryABSTRACT
To evaluate the molluscicidal effects of various water-free formulations of niclosamide ethanolamine salt against Oncomelania hupensis in the field of marshlands along the Yangtze River.The river beach with O. hupensis snails were selected as the test field in the marshland along the Yangtze River in Pukou District, Nanjing City. A molluscicidal experiment was carried out by the mechanical dusting method with the dustable powder (DP), powder-granule (PG), granule (GR) of niclosamide ethanolamine salt respectively. The snail mortality, corrected mortality, and the reduced rate of snails’ density were parallel compared among DP, PG and GR.On the 3rd day after the dusting, the snail mortality rates were 66.67%, 67.24%, and 66.87% in the DP, PG, and GR groups respectively, on the 7th day after the dusting, the snail mortality rates were 75.36%, 79.73%, and 73.97% in the DP, PG, and GR groups respectively, and there was no significant difference among the groups (χ2 = 0.006, 0.895, both P > 0.05). On the 15th day after the dusting, the snail mortality rates were 86.92%, 72.86%, and 71.43% in the DP, PG, and GR groups respectively, and there was a significant difference among the groups (χ2 = 9.709, P < 0.01). The snail mortality in the DP group was significantly higher than that in the PG, and GR groups. The curves of the snail corrected mortality and reduced rate of snails’density presented steadily rising trends in the DP group, but presented falling trends in the PG and GR groups on the 15th day after the dusting.The molluscicidal effect of DP is stable and effective in the marshland along the Yangtze River, but the drift of the powder is still not effectively controlled. It is necessary that the different dosage forms are perfected.
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Objective To investigate the effect of protein phosphatase 5 (PP5) on lipid metabolism in the PP5 knockout (KO) mice.Methods Male PP5 KO and wild type (WT) mice at the age of 6 weeks were used in this study. In order to study the effect of high fat diet ( HFD) feeding, the body weight was measured.The liver histology was examined by HE and oil red O staining.To further verify PP5 functions in the adipogenesis, in vitro experiment was carried out using mouse embryonic fibroblasts (MEF).Western blotting and real-time PCR were performed to quantified the expression of lipid metabolism-related genes in the liver tissues.Results Compared with the WT mice, the body weight gain was slower in the KO mice.The size of the lipid droplets was smaller and the quantity was less in the KO mouse liver tissue.In vitro study revealed that the KO mouse MEF cells showed less differentiated adipocytes with smaller lipid droplets than the WT MEF cells.This observation was further confirmed by detecting the expression of adipogenesis-related genes in the HFD liver.The markers of adipocyte differentiation, such as CD36, AP2, PPARγ2, and Glut4, were significantly decreased, while energy expenditure-related markers, such as phosphorylation of GR and expression of UCP1, were significantly increased.Conclusions Protein phosphatase 5 may play a regulatory role in the mouse lipid metabolism through regulating the de-phosphorylation of p-GR and enhancing the expression of UCP1.
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EPSAH is an exopolysaccharide from Aphanothece halophytica GR02. The present study was designed to evaluate its toxicity and adjuvant potential in the specific cellular and humoral immune responses in ovalbumin (OVA) in mice. EPSAH did not cause any mortality and side effects when the mice were administered subcutaneously twice at the dose of 50 mg·kg(-1). Hemolytic activity in vitro indicated that EPSAH was non-hemolytic. Splenocyte proliferation in vitro was assayed with different concentrations of EPSAH. The mice were immunized subcutaneously with OVA 0.1 mg alone or with OVA 0.1 mg dissolved in saline containing Alum (0.2 mg) or EPSAH (0.2, 0.4, or 0.8 mg) on Day 1 and 15. Two weeks later, splenocyte proliferation, natural killer (NK) cell activity, production of cytokines IL-2 from splenocytes, and serum OVA-specific antibody titers were measured. Phagocytic activity, production of pro-inflammatory cytokines IL-1 and IL-12 in mice peritoneal macrophages were also determined. EPSAH showed a dose-dependent stimulating effect on mitogen-induced proliferation. The Con A-, LPS-, and OVA-induced splenocyte proliferation and the serum OVA-specific IgG, IgG1, and IgG2a antibody titers in the immunized mice were significantly enhanced. EPSAH also significantly promoted the production of Th1 cytokine IL-2. Besides, EPSAH remarkably increased the killing activities of NK cells from splenocytes in the immunized mice. In addition, EPSAH enhanced phagocytic activity and the generation of pro-inflammatory cytokines IL-1 and IL-12 in macrophages. These results indicated that EPSAH had a strong potential to increase both cellular and humoral immune responses, particularly promoting the development of Th1 polarization.
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Animals , Female , Mice , Rabbits , Adjuvants, Immunologic , Cyanobacteria , Chemistry , Immunity, Cellular , Immunity, Humoral , Immunization , Interleukin-12 , Allergy and Immunology , Interleukin-2 , Allergy and Immunology , Killer Cells, Natural , Allergy and Immunology , Mice, Inbred ICR , Ovalbumin , Allergy and Immunology , Polysaccharides , Allergy and Immunology , Th1 Cells , Allergy and Immunology , Th2 Cells , Allergy and ImmunologyABSTRACT
Drug for cholestasis therapy is extremely limited.Ur-sodeoxycholic acid is currently the only FDA approved drug to treat primary biliary cirrhosis,whereas its efficacy is limited to early stage of the disease.Therefore,developing novel drugs re-presents a major goal for both pharmaceutical industry and aca-demic researchers.Targeting nuclear receptors in cholestasis is an intriguing approach since these receptors are critically in-volved in the regulation of bile acid homeostasis.This review summarizes the roles of individual nuclear receptors in cholestasis and evaluates their potential clinical application.
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Purpose: To evaluate the anti-cancer properties of the cyanobacterial extract of Oscillatoria terebriformis Methods: The extract was tested in Human lung cancer cell lines and examined for its effect on cell viability, nuclear morphology and sub-G1 formation. Cell viability was determined by micro culture tetrazolium technique (MTT), nuclear morphology investigated using 4’-6-diamidino-2-phenylindole (DAPI) staining technique, and apoptosis assay using DNA fragmentation. Results: The results showed decreasing cell viability in a concentration-dependent manner. Altered cell morphology after treatment with the extract demonstrated that cells experienced apoptosis. Conclusion: The data demonstrate that Oscillatoria Terebriformis extract induced apoptosis in Human lung cancer A549 cells, and therefore, has a potential as an anti-cancer agent.
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Objective To investigate the effects of GR82334 caudal veins injection(iv)or intrathecal injection(ith)on the increase of dopamine (DA)content in rats anterior cingulate gyrus(ACG)induced by heavy current stimulation of saphenous nerve(SN). Methods Totally 42 male Wi-star rats were randomly divided into six groups,including control group,sham stimulation group,SN stimulation group,GR82334(ith)group,NS (ith)group,GR82334(iv)group,and NS(iv)group. At the end of the study,rats of different groups were sacrificed,then the right side ACG were collected and weighted. ACG samples were then homogenized with 0.1 mol/L perchloric acid solution. After spinning at 10 000 r/min(4℃)for 20 min,20μL of the supernatant were harvest from each sample. High performance liquid chromatography electrochemical detection was used to mea-sure DA content. Results Heavy current stimulation of SN caused obvious increase of the DA content in ACG. GR82334(iv or ith)antagonized the significant increase of DA content in ACG induced by the stimulating SN. However,GR82334(ith)did not completely antagonized the increase of DA content in ACG induced by electric stimulating SN. Conclusion The results indicated that there is connection between SN and the dopami-nergic nervous system in ACG,and SN afferent nociceptive signals can activate ACG dopaminergic neurons to release DA. Peripheral and central NK-1 receptors are involved in the process of significant increase of DA content in ACG induced by SN afferent signals. However,there are other central paths of SN information input to ACG to induce obvious increases of DA content,in which other neurotransmitters and receptors may be involved.
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Objective To examinat the influence of gefitinib combination for sensitive lung cancer A549 and resistant A549/GR cell lines. Methods The sensitive lung cancer A549 and resistant A549/GR cell lines were detected and cultured by Tetrazolium blue(MTT),then received different concentrations of gefitinib,octreotide,cisplatin,5-FU alone and in combination with processing after 24 h,48 h,72 h,the apoptosis rate was detected by flow cytometry,and the synergistic effects of drugs were analysised. Results The combination of sensitive A549 lung cancer and A549/GR resistant cell lines played a synergistic inhibitory effect,compared with alone group,the difference was statistical significance (P<0.05); Tured after 48h, the sensitive lung cancer A549 and resistant A549/GR cell lines in combined groupcul were IC50=(5.3±0.5),(5.4±0.8) mg/L,the single drug group IC50=(20.1±1.2),(20.3±1.4) mg/L,the difference was statistical significance (P<0.05); After the induction of lung cancer A549 and sensitive cell lines and drug A549/GR,the apoptosis rate of control group,monotherapy group,the combined group were statistical significance (P<0.05). Conclusion Gefitinib combination has a synergistic inhibitory effect on cell proliferation,and also has a certain effect on other cancer therapy.
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Background: Radiotherapy has an important role in treatment of oral cancer, but it causes some deleterious effect on healthy cells. Radiation produces free radicals which cause lipo-peroxidation, alteration of protein, and DNA damage, and eventually cell death. This study is designed to evaluate protective role of antioxidants in oral malignancies treated with radiotherapy. Methods: This study is conducted in patients of oral cancer treated with radiotherapy. Patients were divided into two groups, control (n=7) and test (n=9). Patients in control group treated with radiotherapy alone and in test group were supplemented with oral antioxidants throughout the radiotherapy course. Pre and post radiotherapy levels of MDA, SOD and Glutathione reductase were measured in blood and cancerous tissue in both groups and statistically compared. TNM staging before and after radiotherapy and side effects of radiotherapy were also compared in both groups. Results: On statistical comparison of mean difference values of MDA, SOD & GR of control v/s test group, it was noticed that there was a significant reduction in MDA (p<0.05) and significant increase in GR levels (p<0.05) but non significant increase in SOD levels (p>0.05) in test group in comparison to control group for both blood and tissue levels. TNM status of patients improved significantly after radiotherapy in test group. Comparison of side effects between both groups indicated that there was reduction in side effects in test group after radiotherapy. Conclusion: These findings indicated the protective role of antioxidants against free radicals produced in oral malignancies treated with radiotherapy.
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Oxidant imbalance is one of the causative mechanisms of aluminum-induced neurotoxicity. In this study, we investigated aluminum-induced oxidant imbalance in non-neuronal tissues (liver, kidney and testis) and temporal cortex in rats. The differences in adaptations to superoxide and peroxide handling capacities (SPHC) of studied organs due to aluminum insult were also evaluated. Male Wistar rats were exposed to aluminum (10 mg/Kg body wt/day) for 4 weeks through orogastric intubation. Liver showed significant decrease in reduced glutathione level, while significant alteration in lipid peroxidation was observed in temporal cortex in aluminium-exposed animals. Superoxide dismutase activity was significantly altered in liver and temporal cortex and catalase activity significantly reduced in the liver due to aluminum exposure, while glutathione reductase and glutathione peroxidase activities were altered in all the tested organs. Among the organs, glutathione-independent SPHC was relatively higher in liver and kidney, while glutathione-dependent SPHC was relatively higher in testis and temporal cortex. As compared to control, aluminum-exposed rats demonstrated reduction in glutathione-dependent SPHC in temporal cortex and increment of the same in testis, while increment in glutathione-independent SPHC was observed in liver. In conclusion, aluminum-induced alteration in oxidant handling capacity could be the cause of oxidative stress both in the neuronal and non-neuronal tissues.
Subject(s)
Aluminum/poisoning , Aluminum/toxicity , Neurotoxicity Syndromes , Glutathione Reductase/metabolism , Glutathione Peroxidase/metabolism , Liver , Kidney , Superoxides/metabolism , Peroxides/metabolism , Temporal Lobe , TestisABSTRACT
Pyrethroids are a class of neurotoxic pesticides with high selectivity for insects. Fenvalerate is a synthetic pyrethroid pesticide used to protect a variety of crops. Fenvalerate has been reported to exert deleterious effects on non target organisms including mammals. Recently, Fenvalerate was reported to cause liver damage in rats probably by generating oxidative stress while Quercetin, a potential antioxidant, has been reported to posses hepatoprotective activity. Therefore, the aim of the present investigation was to assess the ability of Quercetin to protect liver from Fenvalerate induced toxicity. In the present investigation an effort was made to evaluate the effect of Quercetin and Fenvalerate on hepatic G 6PD, GST and GR. Fenvalerate administration demonstrated significant reduction in the activities of hepatic G-6-PD, GST and GR while rats co treated with Quercetin showed significant recovery in the activities of these antioxidant enzymes.
ABSTRACT
PURPOSE: During oxidative stress, the levels of oxygen free radical increase dramatically, which plays a role in apoptosis, aging and is chemic injury, but also leads to positive effects such as induction of host defense genes and mobilization of ion transport systems. It has been suggested that the advantages of laparoscopic surgery are closely related to the reduced oxidative stress that occurs during laparoscopic cholecystectomy (LC) when compared to open cholecystectomy (OC). This study was conducted to compare oxidative stress markers including total antioxidant status (TAS), superoxide dismutase (SOD) and gluthathione reductase (GR) between the LC group and OC group to determine if these surgical procedures result in different patterns of oxidative stress. METHODS: Our prospective study included fifty patients with symptomatic cholelithiasis and cholecystitis, of whom 25 underwent LC and 25 underwent OC. The plasma levels of oxidative stress markers (TAS, SOD, and GR) were measured preoperatively and on the 1st, 2nd and 3rd postoperative days. RESULTS: The postoperative hospitalization days differed significantly between the two groups (p0.05). An acceptable postoperative decrease in SOD was observed in the OC group, especially after the 2nd postoperative day (p0.05) upon analysis of covariance. A significant postoperative decrease in the level of SOD was observed in the OC group, especially after the 2nd postoperative day (p<0.01), and there was also a significant difference in the serial change in SOD between groups (p=0.020). The level of GR in the OC group decreased significantly on the 2nd postoperative day (p=0.022). Moreover, ANCOVA revealed a significant difference in the serial changes in thelevel of GR between the two groups (p=0.039). CONCLUSION: Our study compared oxidative stress between LC and OC groups based on the levels of TAS, SOD, and GR. We found that minimally invasive surgery, such as laparoscopic cholecystectomy, produced less oxidative stress than open surgery.