Qingquan Lian

Wenzhou University, Yung-chia, Zhejiang Sheng, China

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Publications (29)72.6 Total impact

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    ABSTRACT: Ziram is a widely used fungicide for crops. Its endocrine disrupting action is largely unknown. 11β-hydroxysteroid dehydrogenases, isoforms 1 (HSD11B1) and 2 (HSD11B2), have been demonstrated to be the regulators of the local levels of active glucocorticoids, which have a broad of physiological actions. In the present study, the potency of ziram was tested for its inhibition of rat and human HSD11B1 and HSD11B2. Ziram showed the inhibition of rat HSD11B1 reductase with IC50 of 87.07 µM but no inhibition of human enzyme at 100 M. Ziram showed the inhibition of both rat and human HSD11B2 with IC50 of 90.26 and 34.93 µM, respectively. Ziram exerted a competitive inhibition of rat HSD11B1 when 11-dehydrocorticosterone was used and a mixed inhibition when NADPH was supplied. Ziram exerted a noncompetitive inhibition of both rat and human HSD11B2 when steroid substrates were used and an uncompetitive inhibition when NAD+ was supplied. Increased DDT concentrations antagonized rat and human HSD11B2 activities, suggesting the cysteine residues are associated with the inhibition of ziram. In conclusion, for human, ziram is a selective inhibitor of HSD11B2, implying that this agent may cause excessive glucocorticoid action in local tissues such as kidney, brain, and placenta.
    No preview · Article · Feb 2016 · Chemical Research in Toxicology
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    ABSTRACT: Progesterone and estradiol produced by the human placenta are critical for maintenance of pregnancy and fetal development. In the human placenta, 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) is responsible for the formation of progesterone from pregnenolone and aromatase (CYP19A1) for the production of estradiol from androgen. Insecticide methoxychlor (MXC) and its metabolite hydroxychlor (HPTE) may disrupt the activities of these 2 enzymes. In this study, we investigated the effects of MXC and HPTE on steroid production in human placental JEG-3 cells and on HSD3B1 and CYP19A1 activities. MXC and HPTE inhibited progesterone and estradiol production in JEG-3 cells. MXC and HPTE were potent HSD3B1 inhibitors with the half maximal inhibitory concentration (IC50) values of 2.339 ± 0.096 and 1.918 ± 0.078 μmol/l, respectively. MXC had no inhibition on CYP19A1 at 100 μmol/l, while HPTE was a weak inhibitor with IC50 of 97.16 ± 0.10 μmol/l. When pregnenolone was used to determine the inhibitory mode, MXC and HPTE were found to be competitive inhibitors of HSD3B1. When cofactor NAD+ was used, MXC and HPTE were the noncompetitive inhibitors of HSD3B1. When testosterone was used, HPTE was a mixed inhibitor of CYP19A1. In conclusion, MXC and HPTE are potent inhibitors of human HSD3B1, and HPTE is a weak CYP19A1 inhibitor.
    No preview · Article · Jan 2016 · Pharmacology
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    ABSTRACT: Gossypol is a chemical isolated from cotton seeds. It exists as (+) - or (-) enantiomer and has been tested for anticancer, abortion-inducing, and male contraception. Progesterone formed from pregnenolone by 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) and estradiol from androgen by aromatase (CYP19A1) are critical for the maintenance of pregnancy or associated with some cancers. In this study we compared the potencies of (+) - and (-)-gossypol enantiomers in the inhibition of HSD3B1 and aromatase activities as well as progesterone and estradiol production in human placental JEG-3 cells. (+) Gossypol showed potent inhibition on human placental HSD3B1 with IC50 value of 2.3 μM, while (-) gossypol weakly inhibited it with IC50 over 100 μM. In contrast, (-) gossypol moderately inhibited CYP19A1 activity with IC50 of 23 μM, while (+) gossypol had no inhibition when the highest concentration (100 μM) was tested. (+) Gossypol enantiomer competitively inhibited HSD3B1 against substrate pregnenolone and showed mixed mode against NAD(+). (-) Gossypol competitively inhibited CYP19A1 against substrate testosterone. Gossypol enantiomers showed different potency related to their inhibition on human HSD3B1 and CYP19A1. Whether gossypol enantiomer is used alone or in combination relies on its application and beneficial effects.
    No preview · Article · Dec 2015 · Fitoterapia
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    ABSTRACT: Massive accumulation of amyloid beta (Aβ) has been implicated as a pivotal event in the pathogenesis of Alzheimer's disease. The underlying mechanisms of Aβ-induced neurotoxicity include generation of reactive oxidative species (ROS), inflammation, and neurons loss. Allopregnano-lone (APα), a neurosteroid derive from neuroactive progesterone, has been demonstrated to have neuroprotective properties in vivo and vitro. In the present study, the effects of APα on oxidative damage in Aβ25-35-treated pheochromocytoma (PC12) cells were investigated. Pretreatment of APα significantly attenuated Aβ25-35-induced neuronal death. APα decreased the intracellular ROS generation and reduced lipid peroxidation induced by Aβ25-35. In addition, APα treatment enhanced antioxidant enzyme superoxide dismutase (SOD) activity. This study demonstrates that APα exerts a protective effect against Aβ25-35-induced neurotoxicity in PC12 cells. The protective role of APα likely results from inhibition of oxidative stress.
    No preview · Article · Nov 2015 · International Journal of Clinical and Experimental Medicine
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    ABSTRACT: There is a clear link between epilepsy and depression. Clinical data demonstrate a 30-35% lifetime prevalence of depression in patients with epilepsy, and patients diagnosed with depression have a three to sevenfold higher risk of developing epilepsy. Traditional epilepsy models partially replicate the clinical observations, with the demonstration of depressive traits in epileptic animals. Studies assessing pro-epileptogenic changes in models of depression, however, are more limited. Here, we examined whether a traditional rodent depression model-bilateral olfactory bulbectomy-predisposes the animals towards the development of epilepsy. Past studies have demonstrated increased neuronal excitability after bulbectomy, but continuous seizure monitoring had not been conducted. For the present study, we monitored control and bulbectomized animals by video-EEG 24/7 for approximately two weeks following the surgery to determine whether they develop spontaneous seizures. All seven bulbectomized mice exhibited seizures during the monitoring period. Seizures began about one week after surgery, and occurred in clusters with severity increasing over the monitoring period. These results suggest that olfactory bulbectomy could be a useful model of TBI-induced epilepsy, with advantages of relatively rapid seizure onset and a high number of individuals developing the disease. The model may also be useful for investigating the mechanisms underlying the bidirectional relationship between epilepsy and depression.
    Full-text · Article · Sep 2015 · PLoS ONE
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    ABSTRACT: The capacity of Brown Norway rat Leydig cells to produce testosterone (T) decreases with aging. In a previous study, we reported that a new generation of Leydig cells can be restored in both young and old rat testes after a single injection of ethane dimethanesulfonate (EDS), and that the abilities of the new Leydig cells in young and old rats to produce T were equivalent. Our objective herein was to compare the steroidogenic fate of the new Leydig cells over time. Young (3month-old) and old (18month-old) rats were injected with EDS to eliminate the existing Leydig cells. Ten weeks after EDS, Leydig cells had been restored and T production by the new Leydig cells isolated from young and old rat testes was equivalent. Thirty weeks after EDS treatment of young rats, the ability of the new Leydig cells to produce T had not diminished from 10weeks post-EDS. In contrast, at 30weeks post-EDS, T production by new cells in old rat testes was reduced significantly from the 10-week level. Serum T levels at 10 and 30weeks were consistent with Leydig cell T production. Serum LH levels did not differ in any group. Thus, although the Leydig cells restored to both young and old rats after EDS initially produced T at high, equivalent levels, the cells in the old testes did not maintain this ability. These results suggest that: 1) the cells from which new populations of Leydig cells are derived may differ depending upon the age of the rat; and/or 2) factors extrinsic to the new Leydig cells in young and old testes differ, and it is these differences that are responsible for reductions in T by the newly formed Leydig cells in the testes of old rats. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Aug 2015 · Experimental gerontology
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    Jing Song · Yenji Shen · Jing Zhang · Qingquan Lian
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    ABSTRACT: Propofol (2, 6-diisopropylphenol) is an intravenous sedative-hypnotic agent administered to induce and maintain anesthesia. It has been recently revealed that propofol has anticancer properties including direct and indirect suppression of the viability and proliferation of cancer cells by promoting apoptosis in some cancer cell lines. This study aimed to establish a profile to quantitatively and functionally evaluate the anticancer properties of propofol in three cancer cell lines: non-small cell lung carcinoma cell line A549, human colon carcinoma cell line LoVo, and human breast cancer cell line SK-BR-3. We demonstrated that the expression level of caspase-3, an apoptosis biomarker, significantly increased in a dose-dependent manner after 24-h stimulation with 100 µM propofol in A549 cells, and slightly increased in LoVo cells. However, there was no change in caspase-3 expression in SK-BR-3 cells. High caspase-3 expression in A549 cells may be modulated by the ERK1/2 pathway because phosphorylated ERK1/2 dramatically reduced after propofol treatment. BAX, a major protein that promotes apoptosis in the regulation phase, was highly expressed in A549 cells after treatment with 25 µM propofol. Apoptosis induced by propofol may be associated with cancer cells carrying Kras mutations. Our results suggest that the anti-cancer effects of propofol, which are consistent with those of previous studies, are likely associated with the Kras mutation status. Only Kras mutation in Codon 12 instead of other Kras status has been demonstrated to play an important role in sensitizing the propofol-induced apoptosis in cancer cell lines from our study. These findings may enable us a detailed investigation of propofol/Kras-mediated cancer cell apoptosis in the future.
    Preview · Article · Dec 2014 · PLoS ONE
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    ABSTRACT: Diisononyl phthalate (DINP) is a synthetic material that has been widely used as a substitute for other plasticizers prohibited due to reproductive toxicity in consumer products. Some phthalates have been associated with testicular dysgenesis syndrome in male fetus when female pregnant dams were exposed to them. The present study investigated effects of DINP on fetal Leydig cell function and testis development. Female pregnant Sprague Dawley rats received control vehicle (corn oil) or DINP (10, 100, 500, and 1000 mg/kg) by oral gavage from gestational day (GD) 12 to 21. At GD 21.5, testicular testosterone production, fetal Leydig cell numbers and distribution, testicular gene and protein expression levels were examined. DINP showed dose-dependent increase of fetal Leydig cell aggregation with the low observed adverse-effect level (LOAEL) of 10 mg/kg and multinucleated gonocyte with LOAEL of 100 mg/kg. At 10 mg/kg, DINP also significantly increased fetal Leydig cell size, but inhibited insulin-like 3 and 3β-hydroxysteroid dehydrogenase gene expression and protein levels. DINP inhibited testicular testosterone levels at 1000 mg/kg. The results indicate that in utero exposure to DINP affects the expression levels of some fetal Leydig cell steroidogenic genes, gonocyte multinucleation and Leydig cell aggregation.
    Full-text · Article · Nov 2014 · Toxicology Letters
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    ABSTRACT: To explore the roles of P2Y12 receptor (P2Y12R) in bone cancer pain by observing the changes of inflammatory cytokines (IL-1β, IL-6) after intrathecal injection (i.t.) of P2Y12R antagonist MRS2395. Thirty-two female SD rats were randomly divided into 4 groups (n = 8 each): sham group (group S), MRS2395 group (group M), cancer group (group A) and cancer + MRS2395 group (group MA).Groups S and M received an injection of 10 µl Hank's solution into left tibia medullar cavity while groups A and MA had an injection of Walker 256 mammary cancer cells (10 µl, 2×10(7) cells/ml) into the same place. At Day 9-12 post-inoculation, groups S and A received an injection of saline (0.9%, 15 µl, i.t.) while groups M and MA had MRS2395 (400 pmol/µl, 15 µl, i.t.). Intrathecal catheterization between L3 and L4 was performed immediately after inoculating tumor cells by inserting a small tube into vertebral space. Mechanical withdrawal thresholds were measured on left hind paws before and during 10-minute intervals after dosing. Spinal cords (L4-L6 segments) were removed for determining the expressions of IL-1β and IL-6 by enzyme-linked immunosorbent assay (ELISA) at Day 12 after drug delivery. At 20 min post-injection, mechanical withdrawal thresholds of groups S, M, A and MA were (34.2 ± 5.8), (34.4 ± 5.7), (21.0 ± 2.0) and (25.4 ± 2.3) g respectively at Day 9 post-inoculation (F = 18.679, P < 0.01); mechanical withdrawal thresholds of group A obviously decreased versus groups S and M; mechanical withdrawal thresholds in group MA increased obviously versus group A. The expressions of IL-1β in groups S, M, A and MA were (74.0 ± 18.6), (98.4 ± 17.3), (253.5 ± 66.4) and (146.3 ± 22.3) pg/ml at Day 12 post-inoculation (F = 18.221, P < 0.01); compared with groups S and M, the expression of IL-1β in group A showed a significant up-regulation. Likewise, the expressions of IL-6 were (377.4 ± 65.8), (331.6 ± 67.9), (856.1 ± 53.4) and (596.1 ± 34.9) pg/ml (F = 70.880, P < 0.01) respectively in groups S, M, A and MA; compared with groups S and M, the expression of IL-6 increased obviously in group A. There were significant decreases of IL-1β and IL-6 in group MA versus group A. An intrathecal injection of MRS2395 may alleviate hyperalgesia and inhibit the up-regulated expression of spinal cord inflammatory cytokines in bone cancer rats. And P2Y12 receptor may be involved in the formation of bone cancer pain through regulating the expressions of IL-1β and IL-6.
    No preview · Article · Aug 2014 · Zhonghua yi xue za zhi
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    Lixu Jin · Yuling Chen · Xinlin Mu · Qingquan Lian · Haiyun Deng · Renshan Ge
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    ABSTRACT: Ovarian cancer is a major cause for death of gynecological cancer patients. The efficacy of traditional surgery and chemotherapy is rather compromised and platinum-resistant cancer recurs. Finding new therapeutic targets is urgently needed to increase the survival rate and to improve life quality of patients with ovarian cancer. In the present work, phosphoproteomic analysis was carried out on untreated and gossypol-treated ovarian cancer cell line, HOC1a. We identified approximately 9750 phosphopeptides from 3030 phosphoproteins, which are involved in diverse cellular processes including cytoskeletal organization, RNA and nucleotide binding, and cell cycle regulation. Upon gossypol treatment, changes in phosphorylation of twenty-nine proteins including YAP1 and AKAP12 were characterized. Western blotting and qPCR analysis were used to determine expression levels of proteins in YAP1-related Hippo pathway showing that gossypol induced upregulation of LATS1, which phosphorylates YAP1 at Ser 61. Furthermore, our data showed that gossypol targets the actin cytoskeletal organization through mediating phosphorylation states of actin-binding proteins. Taken together, our data provide valuable information to understand effects of gossypol on protein phosphorylation and apoptosis of ovarian cancer cells.
    Preview · Article · Aug 2014 · BioMed Research International
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    ABSTRACT: Drug resistance poses a major challenge to ovarian cancer treatment. Understanding mechanisms of drug resistance is important for finding new therapeutic targets. In the present work, a cisplatin-resistant ovarian cancer cell line A2780-DR was established with a resistance index of 6.64. The cellular accumulation of cisplatin was significantly reduced in A2780-DR cells as compared to A2780 cells consistent with the general character of drug resistance. Quantitative proteomic analysis identified 340 differentially expressed proteins between A2780 and A2780-DR cells, which involve in diverse cellular processes, including metabolic process, cellular component biogenesis, cellular processes and stress responses. Expression levels of Ras-related proteins Rab 5C and Rab 11B in A2780-DR cells were lower than those in A2780 cells as confirmed by real-time quantitative PCR and western blotting. The short hairpin (sh)RNA-mediated knockdown of Rab 5C in A2780 cells resulted in markedly increased resistance to cisplatin whereas overexpression of Rab 5C in A2780-DR cells increases sensitivity to cisplatin, demonstrating that Rab 5C-dependent endocytosis plays an important role in cisplatin resistance. Our results also showed that expressions of glycolytic enzymes PKM, GPI, ALDO, LDH, and PGK were down-regulated in drug resistant cells, indicating drug resistance in ovarian cancer is directly associated with a decrease in glycolysis. Furthermore, it was found that glutathione reductase were up-regulated in A2780-DR, while vimentin, HSP90, and Annexin A1 and A2 were down-regulated. Taken together, our results suggest that drug resistance in ovarian cancer cell line A2780 is caused by multifactorial traits, including the down-regulation of Rab 5C-dependent endocytosis of cisplatin, glycolytic enzymes and vimentin, and up-regulation of antioxidant proteins, suggesting Rab 5C is a potential target for treatment of drug-resistant ovarian cancer. This constitutes a further step towards a comprehensive understanding of drug resistance in ovarian cancer.
    Preview · Article · Aug 2014 · Molecular & Cellular Proteomics
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    ABSTRACT: Objective: To explore the effect of single-dose dexmedetomidine on recovery period after sevoflurane anesthesia with spontaneous respiration in pediatric patients undergoing cleft lip and palate repair. Methods: A total of 60 American Society of Anesthesiologists (ASA) I-II pediatric patients undergoing cleft lip and palate repair from October to December 2013 were randomly divided into groups D and C (n = 30 each) . Dexmedetomidine 0.5 µg/kg (group D) or an equal volume of normal saline (group C) was ad ministered intravenously over a period of 10 min at 30 min before the end of surgery. Anesthesia was induced and maintained with sevoflurane under spontaneous ventilation. Heart rate, mean arterial pressure (MAP), hemoglobin oxygen saturation (SpO2), respiratory rate, tidal volume (VT) and pressure of end-tidal carbon dioxide (PETCO2) were recorded at the time before induction (T0), 30 min before the end of surgery (T1) , 20 min before the end of surgery (T2), 15 min before the end of surgery (T3), 10 min before the end of surgery (T4), the end of surgery (T5), extubation (T6), 5 min after transferal into post-anesthesia care unit (PACU) (T7) , 1 h after surgery (T8) , extubation time, length of PACU stay, fentanyl consumption and adverse events were all recorded. The incidence and severity of coughing and emergence agitation were assessed. Results: Compared to T0, MAP and heart rate at T1 to T5 all decreased in two groups (P < 0.05). MAP and heart rate at T6 both increased in two groups and group C was higher than group D (P < 0.05). No inter-group differences existed in SpO2, respiratory rate, VT or PETCO2. The incidence of coughing and emergence agitation (30% and 13.3%), fentanyl consumption of group D (0.8 ± 2.1 µg) were all significantly lower than that of group C [(66.7% vs 56.7%) and (4.9 ± 6.50) µg, P < 0.05]. Length of PACU stay in group D was shorter than that in group C [(15 ± 6) vs (23 ± 19) min, P < 0.05]. No inter-group difference existed in extubation time or adverse events. Conclusion: A single intravenous dose of dexmedetomidine is effective in reducing emergence agitation and coughing, shortening length of PACU stay and improving the quality of recovery period after sevoflurane anesthesia in pediatric patients undergoing cleft lip and palate repair.
    No preview · Article · May 2014 · Zhonghua yi xue za zhi
  • Bin Ji · Yuan Han · Qixing Liu · Xuhua Liu · Fanghua Yang · Rui Zhou · Qingquan Lian · Hong Cao · Jun Li
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    ABSTRACT: Objective: To investigate the ameliorative effect of curcumin pretreatment against impaired spatial working memory on global cerebral ischemia-reperfusion rats and to explore its mechanism. Methods: After trained on a modified T-maze, 120 adult SD rats were randomly divided into 5 groups: sham group (S group), cerebral ischemia-reperfusion group (IR group), curcumin group (C group), LPS group (L group) and curcumin+LPS group (C+L group). Rats were treated with drugs or vehicles 1 h before 10 min global cerebral ischemia. Six rats in each group 7 days after reperfusion were tested in T-maze. Six rats in each group were sacrificed at 2 h, 1, 3 and 7 d after reperfusion and their serum or brains were harvested. Brain sections were stained with HE or toluidine blue and neuronal damage was quantified by the average neuronal density of CA1 area. Immunohistochemical staining for hippocampal IL-1β and TNF-α was carried out, levels of serum IL-1β and TNF-α was detected using ELISA procedure. Results: Compared with S group, percentage of T-maze correct responses was decreased (88% ± 12% vs 69% ± 8%, P < 0.05), an extensive pyramidal neurons loss in CA1 area was observed, level of IL-1β (0.26 ± 0.04 vs 0.53 ± 0.06, P < 0.05;48 ± 13 vs 161 ± 31, P < 0.05) and TNF-α (40.244 ± 0.025 vs 0.418 ± 0.036, P < 0.05; 33 ± 4 vs 85 ± 15, P < 0.05) in hippocampi or serum was increased in IR group. Compared with IR group, percentage of T-maze correct responses was increased (78% ± 13%) and average pyramidal neuronal density in CA1 area was increased with an decrease in hippocampi or serum IL-1β (0.44 ± 0.09, 72 ± 19) and TNF-α (0.307 ± 0.047, 57 ± 14) in C group(P < 0.05). Compared with IR group, percentage of T-maze correct responses (61% ± 6%) was decreased with IL-1β (0.86 ± 0.13, 331 ± 51), TNF-α (0.735 ± 0.059, 185 ± 20) in hippocampi and serum was increased in L group (P < 0.05). Compared with L group, percentage of T-maze correct responses (69% ± 12%) and average pyramidal neuronal density in CA1 area was increased with IL-1β (0.69 ± 0.09, 246 ± 24), TNF-α(0.586 ± 0.047, 105 ± 25) in hippocampi and serum was decreased in C+L group (P < 0.05). Conclusion: Curcumin pretreatment improves the impaired spatial working memory in global cerebral ischemia-reperfusion rats by inhibiting proinflammatory cytokines.
    No preview · Article · Apr 2014 · Zhonghua yi xue za zhi
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    ABSTRACT: In pediatric fluid therapy it would be preferable to describe distribution and elimination a fluid bolus based on repetitive hemoglobin (Hb) according to kinetic principles. Pulse CO-Oximetry is a recent advancement in patient monitoring that allows for the continuous noninvasive measurement of Hb (SpHb). The aim of this study was to describe the distribution and elimination of hydroxyethylstarch (HES) 130/0.4 in combination with crystalloids using a noninvasive Hb monitor in two cohorts of young children undergoing minor surgeries under general anesthesia. Two cohorts, 16 children aged 1-3 years and 12 aged 4-6 years, were investigated during anesthesia and minor surgical procedures. They were given a maintenance solution of lactated Ringer's and a fluid bolus of HES 130/0.4, 6 mL/kg over a period of 20 min. The whole procedure lasted 120 min, and SpHb values were measured every 10 min. The SpHb values were used to calculate plasma dilution, net volume, and mean residence time (MRT) of the infused fluid. A total of 377 measured SpHbs generated individual dilution plots that showed variability, particularly for the older cohort. Distribution and elimination rates of the infused fluid were calculated. Mean dilution plots were generated. There were no significant differences in dilution, net volume or MRT between groups. A non invasive Hb analyzer could be used to calculate fluid distribution. The variability in the data can probably be explained by reactions to anesthetic drugs, variability in measurement technique, variability in generating the complex capillary signals, and individual variability in baseline fluid status. The latter finding is important because this is a prerequisite for perioperative fluid planning for each individual.
    No preview · Article · Feb 2014 · International Journal of Clinical Monitoring and Computing
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    ABSTRACT: Previous studies have shown that a low dose of propofol IV bolus had a beneficial effect on intrathecal morphine-induced pruritus in humans. However, its exact mechanism has not been fully understood. In this study, we hypothesized that propofol relieved intrathecal morphine-induced pruritus in rats by upregulating the expression of cannabinoid-1 (CB[1]) receptors in anterior cingulate cortex (ACC). Twenty-four Sprague-Dawley rats were divided into a control group and 20, 40, 80 μg/kg morphine groups to create an intrathecal morphine-induced scratching model. The effects of propofol on intrathecal 40 μg/kg morphine-induced scratching responses were then evaluated. Sixty rats were randomly assigned to control, normal saline, intralipid, and propofol groups, with pruritus behavior observation or killed 8 minutes after venous injection of normal saline, intralipid, or propofol, and brain tissues were then collected for assay. Immunohistochemistry was then performed to identify the expression of CB (1) receptor in ACC, and the concentration of CB(1) receptor in ACC was determined by Western blot analysis. Compared with the control group, rats in the 20, 40, 80 μg/kg morphine groups had higher mean scratching response rates after intrathecal morphine injection (P =0.020, 0.005, and 0.002, respectively). There was a statistical difference between 20 and 40 μg/kg morphine groups at 10 to 15 and 15 to 20 timepoints after intrathecal morphine injection (P = 0.049 and 0.017, respectively). Propofol almost abolished the scratching response that was induced by 40 μg/kg intrathecal morphine injection (F[2, 15] = 46.87, P < 0.001; F[22, 165] = 2.37, P = 0.001). Compared with the intralipid and normal saline groups, the scratching behavior was significantly attenuated in the propofol group (P < 0.001). Compared with control, normal saline, and intralipid groups, the protein expression of CB(1) receptor in ACC (Western blot) in the propofol group increased (0.86 ± 0.21, 0.94 ± 0.18, 0.86 ± 0.13, and 1.34 ± 0.32, respectively, P < 0.001). There was no significant difference among control, normal saline, and intralipid groups. Compared with the control, normal saline, and intralipid groups, the average number of neurons of CB(1) receptor in the ACC area were higher in the propofol group (21.0 ± 1.4, 19.3 ± 1.8, 24.8 ± 7.7, and 37.2 ± 3.3, respectively, P < 0.001). Morphine elicits dose-independent scratching responses after intrathecal injection in rats. Morphine 40 μg/kg intrathecal injection-induced scratching responses can be prevented by propofol. Increased protein expression of CB(1) receptors in ACC may contribute to the reversal of intrathecal morphine-induced scratching.
    No preview · Article · Feb 2014 · Anesthesia and analgesia
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    ABSTRACT: Resveratrol is a polyphenol produced by several plants. It has been demonstrated that it has anti-inflammatory, antitumor, and anti-diabetic effects in animal models. However, its side effects are generally unclear. In the present study, we reported that resveratrol inhibited luteinizing hormone-stimulated androgen production in rat immature Leydig cells. Further analysis demonstrated that it was a competitive inhibitor of rat and human 3β-hydroxysteroid dehydrogenase with IC50 values of 3.87±0.06 and 8.48±0.04μM, respectively. The inhibition on 3β-hydroxysteroid dehydrogenase was specific since it did not inhibit another hydroxysteroid dehydrogenase 17β-hydroxysteroid dehydrogenase 3 at the highest concentration (100μM) tested. In conclusion, resveratrol potentially interferes with androgen biosynthesis of rat Leydig cells.
    No preview · Article · Jan 2014 · Toxicology Letters
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    Binbin Wu · Zipu Yu · Shan You · Yihu Zheng · Jin Liu · Yajing Gao · Han Lin · Qingquan Lian
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    ABSTRACT: Volatile anesthetics are widely used in pediatric anesthesia but their potential neurotoxicity raise significant concerns regarding sequelae after anesthesia. However, whether physiological disturbance during anesthetic exposure contributes to such side effects remains unknown. The aim of the current study is to compare the neurotoxic effects of isoflurane and sevoflurane in 14 day old rat pups under spontaneous breathing or ventilated conditions. Postnatal 14 day rats were assigned to one of five groups: 1) spontaneous breathing (SB) + room air (control, n = 17); 2) SB + isoflurane (n = 35); 3) SB + sevoflurane (n = 37); 4) mechanical ventilation (MV) + isoflurane (n = 29); 5) MV + sevoflurane (n = 32). Anesthetized animal received either 1.7% isoflurane or 2.4% seveoflurane for 4 hours. Arterial blood gases and blood pressure were monitored in the anesthetized groups. Neurodegeneration in the CA3 region of hippocampus was assessed with terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling immediately after exposure. Spatial learning and memory were evaluated with the Morris water maze in other cohorts 14 days after experiments. Most rats in the SB groups developed physiological disturbance whereas ventilated rats did not but become hyperglycemic. Mortality from anesthesia in the SB groups was significantly higher than that in the MV groups. Cell death in the SB but not MV groups was significantly higher than controls. SB + anesthesia groups performed worse on the Morris water maze behavioral test, but no deficits were found in the MV group compared with the controls. These findings could suggest that physiological disturbance induced by isoflurane or sevoflurane anesthesia may also contribute to their neurotoxicity.
    Preview · Article · Jan 2014 · PLoS ONE
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    ABSTRACT: In the present work, metabolomic and redox proteomic analyses were carried out on an untreated- and gossypol-treated ovarian cancer cell line, SKOV3. Gossypol treatment resulted in cell death through oxidative stress. Metabolite analysis showed that gossypol induces a decrease of the cellular levels of GSH, aspartic acid, and FAD. Using a combination of double labeling and LC-MS-MS, we identified changes in thiol-redox states of 545 cysteine-containing peptides from 356 proteins. The frequently occurring amino acid residue immediately before or after the cysteine in these peptides is the non-polar and neutral leucine, valine, or alanine. These redox sensitive proteins participate in a variety of cellular processes. We have characterized the redox-sensitive cysteine residues in PKM2, HSP60, malate dehydrogenase and other proteins that play important roles in metabolism homeostasis and stress responses. The three cysteine residues of HSP60 exhibit different responses to gossypol treatment: an increase of thiol/disulfide ratio for the Cys447 residue due to a decrease of the cellular GSH level, and a decrease of thiol/disulfide ratios for Cys442 and Cys237 residues due to oxidation and sulfation. This study suggests that thiol/disulfide ratios are dependent on the level of cellular GSH. Our data provide a valuable resource for deciphering the redox regulation of proteins and for understanding gossypol-induced apoptosis in ovarian cancer cells.
    No preview · Article · Mar 2013 · Molecular BioSystems
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    ABSTRACT: Post-operative cognitive dysfunction has been widely observed, especially in older patients. An association of post-operative cognitive dysfunction with the neurodegenerative diseases, such as Alzheimer's disease, has been suggested. Neuroinflammation contributes to Alzheimer pathology, through elevated pro-inflammatory cytokines and microglial activation in the CNS leading to neuronal damage, synaptic disruption and ultimately cognitive dysfunction. We compare the effects of three different, clinically-used, anesthetics on microglial activation with, and without, the prototypical inflammatory trigger, lipopolysaccharide (LPS). Microglial BV-2 cell cultures were first exposed to isoflurane, sevoflurane (each at 2 concentrations) or propofol for 6 h, and cytokine levels measured in lysates and media. The same experiments were repeated after 1 h LPS pre-treatment. We found; 1) anesthetics alone have either no or only a small effect on cytokine expression; 2) LPS provoked a large increase in microglia cytokine expression; 3) the inhaled anesthetics either had no effect on LPS-evoked responses or enhanced it; 4) propofol nearly eliminated the LPS pro-inflammatory cytokine response and improved cell survival as reflected by lactate dehydrogenase release. These data suggest that propofol may be a preferred anesthetic when it is desirable to minimize neuroinflammation.
    Full-text · Article · Jan 2013 · PLoS ONE
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    ABSTRACT: As a widely used intravenous short-acting anesthetic, propofol is recently indicated by clinical and animal studies for its abuse potential, but the mechanism underlying propofol abuse is largely unknown. This study examined the contribution of dopamine receptor subtype (D1 and D2 receptors) and neuroanatomical locus (i.e. nuclear accumbens) in maintenance of propofol self-administration in rats. After the acquisition and maintenance of self-administration of propofol (1.7 mg/kg/infusion) under a fixed ratio (FR1) schedule of reinforcement over 14 days, rats were treated by either intraperitoneal injection or intra-nucleus accumbens (NAc) injection of D1 receptor antagonist (SCH23390) or D2 receptor antagonists (spiperone and eticlopride) 10 minutes prior to the subsequent propofol self-administration. We demonstrated i) systemic administration of SCH23390 (10, 30, 100 g/kg, i.p.) dose-dependently decreased the rate of propofol-maintained self-administration, suggesting a critical role of D1 receptor in mediating propofol self-adminstration; ii) the blockade of the propofol self-administration by SCH23390 was specific since spiperone and eticlopride did not affect propofol self-administration and SCH23390 at these doses did not affect food-maintained responding under an FR5 schedule; iii) intra-accumbenal injection of SCH23390 (2.5ug/site) but not eticopride (3.0ug/site) attenuated the propofol self-administration, localizing nuclear accumbal D1 receptors as a critical locus in the reinforcement of propofol. Together, these findings provide the first direct evidence that D1 receptors in nuclear accumbens play an important role in the maintenance of propofol self-administration.
    No preview · Article · Nov 2012 · Neuroscience

Publication Stats

135 Citations
72.60 Total Impact Points

Institutions

  • 2014-2015
    • Wenzhou University
      Yung-chia, Zhejiang Sheng, China
  • 2005-2014
    • Wenzhou Medical College
      • • Department of Pharmacology
      • • Department of Anesthesiology
      Yung-chia, Zhejiang Sheng, China
  • 2006
    • Huazhong University of Science and Technology
      • Department of Anesthesiology
      Wu-han-shih, Hubei, China