Geniposide improves depression-like behavior in prenatal stress male offspring through restoring HPA axis- and glucocorticoid receptor-associated dysfunction.

AIMS: Prenatal stress (PS) has an important impact on the brain development of offspring, which can lead to attention deficits, anxiety and depression in offspring. Geniposide (GE) is a kind of iridoid glycoside extracted from Gardenia jasminoides Ellis. It has various pharmacological effects and has been proved that have antidepressant effects. The aim of this study was to investigate the effect of GE on depression-like behavior in PS-induced male offspring mice and explore the possible molecular mechanisms. METHODS: We used a prenatal restraint stress model, focusing on male PS-induced offspring mice to study the effects of GE. KEY FINDINGS: The results showed that GE administration for 4 weeks significantly improved the depression-like behavior in PS offspring mice, which was manifested by markedly increasing the sucrose preference of PS offspring and the activity in the open field test, and reducing the immobility time in the forced swimming test. In addition, GE significantly reduced the levels of hypothalamic-pituitary-adrenal (HPA) axis-related hormones and exceedingly increased the protein expression of MAP2 and GAP43 in PS offspring. Furthermore, GE increased Glucocorticoid receptors (GR) nuclear translocation in the hippocampus of PS offspring, and enhanced the expression of synaptic plasticity-related proteins. CONCLUSION: The results of this study showed that GE exerts antidepressant effects in male PS offspring mice by regulating the HPA axis, GR function and proteins related to synaptic plasticity.

GDH promotes isoprenaline-induced cardiac hypertrophy by activating mTOR signaling via elevation of α-ketoglutarate level.

Numerous studies reveal that metabolism dysfunction contributes to the development of pathological cardiac hypertrophy. While the abnormal lipid and glucose utilization in cardiomyocytes responding to hypertrophic stimuli have been extensively studied, the alteration and implication of glutaminolysis are rarely discussed. In the present work, we provide the first evidence that glutamate dehydrogenase (GDH), an enzyme that catalyzes conversion of glutamate into ɑ-ketoglutarate (AKG), participates in isoprenaline (ISO)-induced cardiac hypertrophy through activating mammalian target of rapamycin (mTOR) signaling. The expression and activity of GDH were enhanced in cultured cardiomyocytes and rat hearts following ISO treatment. Overexpression of GDH, but not its enzymatically inactive mutant, provoked cardiac hypertrophy. In contrast, GDH knockdown could relieve ISO-triggered hypertrophic responses. The intracellular AKG level was elevated by ISO or GDH overexpression, which led to increased phosphorylation of mTOR and downstream effector ribosomal protein S6 kinase (S6K). Exogenous supplement of AKG also resulted in mTOR activation and cardiomyocyte hypertrophy. However, incubation with rapamycin, an mTOR inhibitor, attenuated hypertrophic responses in cardiomyocytes. Furthermore, GDH silencing protected rats from ISO-induced cardiac hypertrophy. These findings give a further insight into the role of GDH in cardiac hypertrophy and suggest it as a potential target for hypertrophy-related cardiomyopathy.

PKC-ζ Aggravates Doxorubicin-Induced Cardiotoxicity by Inhibiting Wnt/ß-Catenin Signaling.

Doxorubicin (Dox) is a chemotherapeutic drug used to treat a wide range of cancers, but its clinical application is limited due to its cardiotoxicity. Protein kinase C-ζ (PKC-ζ) is a serine/threonine kinase belonging to atypical protein kinase C (PKC) subfamily, and is activated by its phosphorylation. We and others have reported that PKC-ζ induced cardiac hypertrophy by activating the inflammatory signaling pathway. This study focused on whether PKC-ζ played an important role in Dox-induced cardiotoxicity. We found that PKC-ζ phosphorylation was increased by Dox treatment in vivo and in vitro. PKC-ζ overexpression exacerbated Dox-induced cardiotoxicity. Conversely, knockdown of PKC-ζ by siRNA relieved Dox-induced cardiotoxicity. Similar results were observed when PKC-ζ enzyme activity was inhibited by its pseudosubstrate inhibitor, Myristoylated. PKC-ζ interacted with ß-catenin and inhibited Wnt/ß-catenin signaling pathway. Activation of Wnt/ß-catenin signaling by LiCl protected against Dox-induced cardiotoxicity. The Wnt/ß-catenin inhibitor XAV-939 aggravated Dox-caused decline of ß-catenin and cardiomyocyte apoptosis and mitochondrial damage. Moreover, activation of Wnt/ß-catenin suppressed aggravation of Dox-induced cardiotoxicity due to PKC-ζ overexpression. Taken together, our study revealed that inhibition of PKC-ζ activity was a potential cardioprotective approach to preventing Dox-induced cardiac injury.

Paeoniflorin ameliorates oxidase stress in Glutamate-stimulated SY5Y and prenatally stressed female offspring through Nrf2/HO-1 signaling pathway.

BACKGROUND: Prenatal stress (PS) can cause brain retardation, reduce the learning and memory ability of the offspring and significantly increase the incidence of depression in offspring. Paeoniflorin (PF), a kind of monoterpenoid glycoside, is one of the main active ingredients of Chinese Medicine Paeonia lactiflora Pall, has anti-inflammation and potential neuroprotective effects. However, few reports have shown that the neuroprotective effects of PF are exerted through ameliorating Glutamate toxicity in vivo and in vitro. METHODS: Here, we used a prenatal restraint stress model and Glu-induced excitotoxic neurotoxicity in SH-SY5Y cells to study the effects of PF. RESULTS: Our results showed that PF can ameliorate learning and memory impairments and increases the density of hippocampal neurons, typical Golgi-positive pyramidal cells, and neuronal Neurogranin (Ng) expression in PS rat offspring. Furthermore, PF can significantly up-regulate the decrease of Glu-induced SH-SY5Y cell viability. At the same time, PF can significantly reduce apoptosis, ROS, NO levels, and intracellular Ca2+ concentration, and significantly inhibit the increase of mitochondrial membrane potential. Besides, PF significantly increased the expression of Nrf2 and iNOS, decreased p-JNK/JNK, p-P38/P38, Bax/Bcl-2, active-caspase-3, and active-caspase-9. CONCLUSIONS: Our results demonstrate that PF may be an effective treatment in preventing the development of PS-induced learning and memory impairment and have therapeutic potential in Glu-related neurological diseases.

Neuroprotective effects of aucubin on hydrogen peroxide-induced toxicity in human neuroblastoma SH-SY5Y cells via the Nrf2/HO-1 pathway.

BACKGROUND: When redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis. PURPOSE: The present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (H2O2)-induced injury in SH-SY5Y cells in vitro. METHODS: SH-SY5Y cells were simultaneously treated with AU and H2O2 for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry. RESULTS: The results showed that AU can significantly increase the H2O2-induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that H2O2 stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In H2O2-induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways. CONCLUSION: These results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways.

Icariin reduces Glu-induced excitatory neurotoxicity via antioxidative and antiapoptotic pathways in SH-SY5Y cells.

Excessive glutamate (Glu) can lead to significant effects on neural cells through the generation of neurotoxic or excitotoxic cascades. Icariin (ICA) is a main active ingredient of Chinese Medicine Berberidaceae epimedium L., and has many biological activities, such as antiinflammation, antioxidative stress, and anti-depression. This study aims to evaluate the effect of ICA on Glu-induced excitatory neurotoxicity of SH-SY5Y cells. The cell viability assay was evaluated by the CCK-8 assay. The apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential were assessed by flow cytometry. Intracellular Ca2+ concentration was determined by using the fluorescent probe Fluo-3. Protein expression was detected by western blotting analysis. ICA can significantly enhance the SH-SY5Y cell viability reduced by Glu. At the same time, ICA can significantly reduce apoptosis, ROS, nitric oxide (NO) levels, and intracellular Ca2+ concentration, and significantly inhibit the increase of mitochondrial membrane potential. In addition, ICA significantly increased the expression of P47phox and iNOS, decreased p-JNK/JNK, p-P38/P38, Bax/Bcl-2, active caspase-3, and active caspase-9. These results indicate that ICA may reduce the excitatory neurotoxicity of Glu-induced SH-SY5Y cells through suppression of oxidative stress and apoptotic pathways, suggesting that ICA could be a potential therapeutic candidate for neurological disorders propagated by Glu toxicity.

Paeoniflorin ameliorates depressive-like behavior in prenatally stressed offspring by restoring the HPA axis- and glucocorticoid receptor- associated dysfunction.

BACKGROUND: Prenatal stress (PS) can increase the risk of nervous, endocrine and metabolic diseases and induce depression in offspring. Paeoniflorin (PA) is an amorphous glucoside isolated from the aqueous extract of roots of the peony plant (Paeonia lactiflora Pall.) and exerts various pharmacological effects in the nervous system. METHODS: Male prenatally stressed offspring were used to investigate the antidepression-like effects and possible mechanism of PA. We measured animal behavior, HPA axis, Nissil staining, and Ng expression. Additionally, we assessed the modulation of hippocampal glucocorticoid receptors (GR) nuclear translocation and SNARE complex expression by western blotting. RESULTS: The results showed that administration of PA (15, 30, and 60 mg/kg/day, i.g.) for 28 days markedly increased sucrose intake and decreased the immobility time and the total number of crossings, center crossings, rearing, and grooming in male PS offspring. Moreover, PA significantly reduced the serum corticosterone (CORT), adrenocorticotropin (ACTH), corticotropin-releasing hormone (CRH) and hippocampal glutamate (Glu) levels in male PS offspring, which were stimulated by an increase of GR nuclear translocation. Furthermore, PA markedly increased neurogranin (Ng) protein expression in the hippocampus CA3 region in offspring. PA also markedly decreased hippocampal Glu by inhibiting SNAP25, VAMP2, Syntaxin1a and related protein expression; SNARE complex formation; and EAAT2/3, NR1, NR2A, and FKBP5 protein expression. CONCLUSIONS: Taken together, the results of this study show that PA has antidepression-like effects in male PS offspring, partially due to the HPA axis, GR dysfunction and Glu transport system.

Protective Effects of Total Alkaloids from Menispermum dauricum against Airway Inflammation in Asthmatic Mice.

Menispermum dauricum is widely used to treat respiratory inflammation, including laryngopharyngitis, tonsillitis, tracheitis, and bronchitis. Total alkaloids isolated from M. dauricum have shown a variety of beneficial bioactivities. However, available data on the effects of M. dauricum total alkaloids against allergic asthma has not been reported. In present study, the protective effect of M. dauricum total alkaloids was evaluated by using an ovalbumin-induced in vivo model of asthma. The asthma model was prepared by sensitizing and challenging mice with ovalbumin, and M. dauricum total alkaloids (100, 200, and 400 mg/kg) were administrated to asthmatic mice by gavage. Histopathological analysis of pulmonary changes was detected by hematoxylin and eosin, and periodic acid-schiff staining. Inflammatory cell counts were determined in bronchoalveolar lavage fluid. Total immunoglobulin E and ovalbumin-specific immunoglobulin E levels in serum, and T-helper 2 cytokines and chemokine levels in bronchoalveolar lavage fluid were detected by an ELISA. Histological results demonstrated that M. dauricum total alkaloids significantly attenuated pulmonary inflammation in asthmatic mice. M. dauricum total alkaloid treatment exhibited marked effects on asthmatic mice in reducing inflammatory cell counts, decreasing interleukin-4, interleukin-5, and interleukin-13 concentrations, and downregulating TNF-α and eotaxin levels in bronchoalveolar lavage fluid. In addition, M. dauricum total alkaloids could also inhibit the elevated serum levels of total immunoglobulin E and ovalbumin-specific immunoglobulin E. These findings confirmed that M. dauricum total alkaloids could suppress airway inflammation in ovalbumin-induced asthma through regulating the T-helper 2 response and chemokine level. M. dauricum total alkaloids may be a potential ethnopharmacological agent for asthmatic patients.

Icariin ameliorates learning and memory impairments through ERK/CaMKIIα/CREB signaling and HPA axis in prenatally stressed female offspring.

BACKGROUND: Prenatal stress (PS) leads to a wide variety of behavioral and emotional aberration observed in later life, particularly in the impairment of spatial learning and memory in offspring. Icariin (ICA) is a naturally occurring furanocoumarin and exhibits many pharmacological properties, including potent improvement on learning and memory. PURPOSE: We pretend to investigate the improvement of ICA on learning and memory impairment in PS. METHODS: Female PS offspring rats were used to explore the effects of ICA on learning and memory impairment. After 28 days of ICA (20, 40 and 80 mg/kg/day) treatment, we measured Morris water maze and 8-Arm Maze, the HPA axis and the related pathway in the hippocampus. RESULTS: We reported that ICA ameliorated the spatial learning and memory and working memory impairment in the female offspring rats. Correspondingly, ICA prevented adverse changes in the dendritic morphology of CA3 pyramidal neurons in the hippocampus. ICA significantly decreased the serum adrenocorticotropin, corticotropin-releasing hormone and corticosterone levels in offspring rats exposed to PS, associated with increased GR expression. Additionally, ICA treatment significantly increased the neurogranin (Ng) and c-fos protein expression of hippocampus in the offspring rats. Furthermore, the protein of relative content of p-EKR/ERK, p-CaMKIIα/CaMKIIα, p-CREB/CREB were remarkably increased after ICA treatment in the offspring rats. CONCLUSION: Taken together, ICA may be an effective therapeutic for learning and memory dysfunction in female offspring exposed to PS, its neuroprotective effect was mediated in part by normalizing the HPA axis and up-regulating of ERK/CaMKIIα/CREB signaling, Ng and c-fos protein.

Associations between ADIPOQ polymorphisms and coronary artery disease: a meta-analysis.

BACKGROUND: Whether adiponectin (ADIPOQ) polymorphisms are associated with coronary artery disease (CAD) remain controversial. Therefore, we performed this meta-analysis to better explore potential roles of ADIPOQ polymorphisms in CAD. METHODS: PubMed, Web of Science, Embase and CNKI were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Totally 45 studies were included for pooled analyses. A significant association with the susceptibility to CAD was detected for rs2241766 (dominant model: p = 0.0009, OR = 0.82, 95%CI 0.73-0.92; recessive model: p = 0.04, OR = 1.29, 95%CI 1.02-1.64; allele model: p < 0.0001, OR = 0.80, 95%CI 0.73-0.88) polymorphism in overall population. Further subgroup analyses by ethnicity showed that rs1501299 polymorphism was significantly associated with the susceptibility to CAD in East Asians, whereas rs2241766 polymorphism was significantly associated with the susceptibility to CAD in Caucasians, East Asians and South Asians. CONCLUSIONS: Our findings indicated that rs1501299 and rs2241766 polymorphisms both affect the susceptibility to CAD in certain populations.

Involvement of SNARE complex in the hippocampus and prefrontal cortex of offspring with depression induced by prenatal stress.

BACKGROUND: Prenatal stress (PS) exposure can cause depression-like behavior in offspring, and maladaptive responses including physiological and neurobiological changes. Glutamate neurotransmission is implicated in effects of PS and in antidepressant mechanisms; however, the mechanisms underlying its involvement remain unclear. In the synapse, the formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is essential for vesicular docking and neurotransmitter release. METHODS: To explore effects of PS on the SNARE complex, pregnant rats were assigned to a control or PS group. Both male and female offspring in each group were used in this study. PS rats were exposed to restraint stress three times daily for 45 min on days 14-20 of pregnancy. RESULTS: In the PS offspring, the expression of the SNARE protein SNAP-25, vesicle-associated membrane protein (VAMP)-2, and Syntaxin 1a was significantly increased in the hippocampus and prefrontal cortex. These observations were associated with increased levels of proteins that chaperone SNARE complex formation, including Munc-18, α-synuclein, CSPα, complexin1, and complexin2. Immunoblotting of hippocampal and prefrontal cortex homogenates revealed significantly increased SNARE complex formation. vGluT1 protein expression was also significantly increased in the offspring. Additionally, PS was associated with increased mRNA expression of VAMP1, VAMP2, SNAP25, Syntaxin1a, and Syntaxin1b in the hippocampus and prefrontal cortex. Increased monomeric SNARE proteins, SNARE complex formation, vesicle-associated proteins, and vGluT1 may explain the increase in glutamate and its downstream excitotoxicity. CONCLUSIONS: These results support the hypothesis that glutamate release and vesicular glutamate transporters play a role in PS-induced depression-like behavior of rat offspring.

Ferulic acid inhibits H2O2-induced oxidative stress and inflammation in rat vascular smooth muscle cells via inhibition of the NADPH oxidase and NF-κB pathway.

Ferulic acid (FA) is a dietary phenolic acid and has a wide range of therapeutic effects, including anti-aging, antitumor activity and antihypertensive effects. The aim of present study was to evaluate the inhibitory effects of FA on cell inflammation and oxidative stress against hydrogen peroxide (H2O2)-induced injury in rat vascular smooth muscle cells (VSMCs) in vitro. VSMCs were pretreated with FA 2h before H2O2 incubation. The results suggested that FA inhibited H2O2-induced cell injury by reducing the MDA and increasing the SOD activity and GSH content. In rat VSMCs exposed to H2O2, FA increased the cell viability and restored the mitochondrial membrane depolarization. The level of ROS generation was reduced by pretreatment with FA through inhibiting the expression of NADPH oxidase and down-regulating MAPK and AKT pathways. We found that H2O2 stimulated the production of IL-6, IL-1ß, TNF-α and NO, which could be reduced by pretreatment with FA through inhibiting the p-NF-κB as well as the iNOS expression. In conclusion, our results show that FA may serve as a novel drug in the treatment of these pathologies by inhibiting NADPH oxidase and NF-κB and subsequently decreasing VSMC oxidative stress and inflammation. These suggest that the inhibitory effect of FA on VSMC inflammation and oxidative stress is partially attributed to depressing NADPH and NF-κB expressions in VSMCs, decreasing the ROS production and reducing apoptosis of VSMCs.

Tenofovir rescue therapy in pregnant females with chronic hepatitis B.

AIM: To evaluate the safety and efficacy of tenofovir monotherapy in pregnant females resistant to lamivudine or telbivudine. The effect of tenofovir on the fetus was also assessed. METHODS: The clinical data of 17 females were reviewed in this study. Adverse events and pregnancy outcomes from January 1, 2011 to June 30, 2013 were evaluated in the Department of Gynecology and Obstetrics of Beijing Ditan Hospital, Capital Medical University, Beijing, China. These pregnant females developed lamivudine (LAM)- or telbivudine (LdT)-resistant chronic hepatitis B and received tenofovir (TDF) therapy (300 mg/d), and its curative effect, maternal and perinatal adverse events, fetal growth and development, and neonatal prognosis were evaluated. RESULTS: The median hepatitis B virus (HBV) DNA level in the pregnant females with LAM or LdT resistance was 5.9 (range, 4.2-7.2) log10 copies/mL before the initiation of TDF. Ten of these females had abnormal alanine aminotransferase (ALT) levels. The patients were treated with TDF for a median of 24 wk (range, 12-40 wk). Fourteen females (82.4%) had an HBV DNA level of <500 copies/mL at the time of delivery. This decrease was statistically significant (P<0.0001). Serum ALT levels were normalized in all subjects with an elevated serum ALT level at baseline (P=0.0003). There were no significant changes in serum creatinine and phosphorus levels during TDF treatment. In addition, no adverse events related to TDF treatment were observed. Seventeen females delivered 17 live infants, and all infants had good Apgar scores. The mean birth weight was 3226.5±331.7 g, and the mean length at birth was 50.4±1.1 cm. The growth and development of the infants was normal at birth, and no infants had birth defects related to TDF treatment. Eleven infants completed HBV vaccination and had no evidence of vertical transmission. CONCLUSION: The use of TDF in pregnant females with chronic HBV and LAM or LdT resistance was safe and effective.

Effects of imperatorin, the active component from Radix Angelicae (Baizhi), on the blood pressure and oxidative stress in 2K,1C hypertensive rats.

The 2-kidney, 1-clip (2K,1C) model of hypertension was used to investigate the potential antihypertensive and antioxidant effect of imperatorin extracted from the root of radix angelicae. After 10 weeks treatment of imperatorin, mean blood pressure (MBP) of 2K,1C hypertensive rats was obtained, and superoxide dismutase (SOD), nitric oxide (NO) and nitric oxide synthase (NOS) were measured. Malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CATA), xanthine oxidase (XOD), angiotensinII (Ang II) and endothelin (ET) levels of kidney were evaluated with commercial kits. Nicotinamide adenine dinucleotidephosphate (NADPH) oxidase subunits of the renal cortial tissues were determined by RT-PCR and Western blot. 8-Iso-prostaglandin F2α (8-iso-PGF2α) of 24h urinary excretion was also measured by ELISA. MBP was significantly reduced by treatment with IMP (6.25, 12.5 and 25 mg/kg/day, i.g.) in 2K,1C hypertensive rats. Meanwhile, we found that renal CATA and XOD activities, GSH levels, plasma NO and NOS contents were significantly increased in IMP-treated groups. Plasma ET, renal Ang II levels, MDA and the 24h urinary excretion of 8-iso-PGF2α in the IMP treated group were lower than control SD group. After that, we found the mRNA expressions and protein levels of NADPH oxidase subunits in the clipped kidney were markedly reduced after IMP treated in 2K,1C hypertensive rats. IMP showed antihypertensive and antioxidant effects in the renal injury of renovascular hypertensive rats, suggesting that IMP could be of therapeutic use in preventing renal injury related hypertension.

Effects of acute combined serotonin and dopamine depletion on cue-induced drinking intention/desire and cognitive function in patients with alcohol dependence.

BACKGROUND: Alcohol cues can precipitate the desire to drink and cause relapse in recovering alcohol-dependent patients. Serotonin and dopamine may play a role in alcohol cue-induced craving. Acute combined tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe) depletion (CMD) in the diet attenuates the synthesis of serotonin and dopamine in the human brain. However, no study of the effects of acute CMD has been previously conducted. Therefore, we investigated whether the attenuation of serotonin and dopamine synthesis changes cue-induced alcohol craving in recently abstinent alcoholics. METHODS: In this double-blind, randomized, placebo-controlled, crossover design, 12 male patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for alcohol dependence were divided into two conditions: (1) monoamine depletion (i.e., consumption of a concentrated amino acid beverage that resulted in a rapid and significant decrease in plasma-free Tyr/Phe/Trp) and (2) balanced condition (i.e., consumption of a similar beverage that contained Tyr/Phe/Trp). The participants were scheduled for two experimental sessions, with an interval of ≥7 days. The cue-induced craving test session was conducted 6h after each amino acid beverage administration. Drinking urge, blood pressure, heart rate, working memory, and attention/psychomotor performance were assessed before and after administration. RESULTS: Compared with the balanced condition, the monoamine depletion condition significantly increased drinking intention/desire and diastolic blood pressure. Cognitive performance was not different between the two conditions. CONCLUSIONS: Acute combined serotonin and dopamine depletion may increase drinking intention/desire and diastolic blood pressure without influencing cognitive function.

Role of store-operated calcium entry in imperatorin-induced vasodilatation of rat small mesenteric artery.

Store-operated Ca(2+) entry (SOCE) has recently been proposed to contribute to Ca(2+) influx in vascular smooth muscle cells (VSMCs). Imperatorin is known for its potent vasodilatory effects as a dietary furanocoumarin. The study was designed to examine the hypothesis that SOCE have a functional role in imperatorin-induced vasodilation. Small mesenteric resistance arteries and mesenteric VSMCs were obtained from rats. Isometric tensions of isolated artery rings were measured by a sensitive myograph system. Laser scanning confocal microscopy was used to determine the intracellular Ca(2+) concentration of fluo-3-loaded VSMCs. Imperatorin (1-100 µM) relaxed artery rings precontracted by phenylephrine in a concentration-dependent manner. In cultured mesenteric VSMCs, passive store depletion by thapsigargin and active store depletion by phenylephrine both induced Ca(2+) influx due to SOCE. Imperatorin didn't inhibit SOCE-mediated increases in cytosolic Ca(2+) levels evoked by the emptying of the stores. In isolated artery rings, imperatorin didn't inhibit SOCE-induced contractions due to store depletion. Our results exclude SOCE mechanism of vasodilatation by imperatorin. But imperatorin is partly similar with nifedipine in vasorelaxation effect.

[Significance of serological test of blood group in nonmyeloablative allogeneic peripheral blood stem cell transplantation of patients with acute leukemia].

The purpose of this study is to explore the clinical significance of RBC blood group serological test in nonmyeloablative allogeneic peripheral blood stem cell transplantation (NAPBSCT) of ABO group incompatibility in 4 patients with acute leukemia. ABO and MN blood group of donors and recipients were determined by hemagglutination test and Rh blood group by Diana Gel phenotype Rh card. The changes of blood group in recipients were observed and implant of donor cells was monitored by short tandem repeat-PCR method. The results showed that in 2 cases of 4 recipients the marrow cells appeared mixed chimera of donor and recipient cells, and blood group changed to donor type in 1 of the 2 cases on 100 days after transplantation. In another 2 cases, the marrow cells appeared mixed chimera without blood group chimera on 154 days after transplantation, and rejection of the transplant occurred in 1 of the 2 cases. The determination of hemagglutinin titer showed that the implant rate of donor cells was lower in the recipients with higher hemagglutinin titer and blood group chimera did not appear, conversely, the implant rate was higher in the recipients with lower titer and blood group chimera appeared early. It is concluded that examination of RBC blood group in NAPB SCT can indirectly reflect effectiveness of transplantation, contribute to decide the intensity of conditioning protocol and immunosuppressive therapy after transplantation, estimate prognosis and guide blood transfusion during transplantation.