OBJECTIVE Genetic variation in histamine H2 receptor(H2R)and H2R ligands are linked to schizophrenia,however little is known about how H2R contributes to pathogenesis of schizophrenia.Here,we detected a decreased expr...OBJECTIVE Genetic variation in histamine H2 receptor(H2R)and H2R ligands are linked to schizophrenia,however little is known about how H2R contributes to pathogenesis of schizophrenia.Here,we detected a decreased expression of H2R in medial prefrontal cortex(mPFC)glutamatergic neurons in schizophrenia patients.METHODS AND RESULTS Selective knockout of H2R gene(Hrh2)in glutamatergic neurons induced schizophrenia-like behaviors including sensorimotor gating deficit,increased locomotor activity,social withdrawal and anhedo⁃nia in behavior tests,as well as reduced sponta⁃neous firing of mPFC glutamatergic neurons in electrophysiological tests.Selective deletion of the Hrh2 in mPFC glutamatergic neurons but not hippocampus glutamatergic neurons also induced such schizophrenia-like behaviors.Patch-clamp electrophysiology establishes that H2R deficiency reduced the intrinsic excitability of glutamatergic neurons by up-regulation of hyperpolarization activated cyclic nucleotide-gated channels.Fur⁃thermore,either overexpression of H2R in gluta⁃matergic neurons or activation of H2R in the mPFC reversed the MK-801-induced schizophrenia-like symptoms.CONCLUSION H2R can serve as a novel drug target given that functional deficiency of this receptor in mPFC glutamatergic neurons may be crucial for the pathogenesis of schizo⁃phrenia.H2R agonists can be viewed as drug candidates for the treatment of schizophrenia.展开更多
Objective:To delineate the comparative immunomodulatory roles of H1R-H4R in antibody generation profile in rabbit model.Methods:The cohort comprised of eight groups containing 18(9 male and 9 female) rabbits in each g...Objective:To delineate the comparative immunomodulatory roles of H1R-H4R in antibody generation profile in rabbit model.Methods:The cohort comprised of eight groups containing 18(9 male and 9 female) rabbits in each group.GroupⅠremained non-immunized and received only vehicle(sterile distilled water,1 mL/kg×b.i.d.) intramuscularly.GroupⅡreceived vehicle (1 mL/kg×b.i.d.) while GroupsⅢ-Ⅶ(drugs-treated) received subcutaneous histamine (100μg/kg×b.i.d.),and intramuscular H1R-antagonist(pheniramine,10 mg/kg×b.i.d.), H2R-antagonist(ranitidine,10 mg/kg×b.i.d.),H3R-antagonist(iodophenpropit,1μg/kg×b.i.d.) and H4R-antagonist(JNJ 7777120,10μg/kg×b.i.d.),and GroupⅧDMSO(1 mL/kg×b.i.d.),respectively for 10 days(starting from day 1).They were subsequendy immunized with intravenous injection of sheep red blood cells(SRBC) at day 3.The estimation of serum Igs,IgM and IgG were done by ELISA,and observed at day 0(pre-immunization),and 7,14,21,28 and 58(post-immunization).Results:It was shown that histamine and HRs-antagonists could influence a detectable antibody response to SRBC as early as day 7-post-immunization(post-Ⅰ), which lasted until day 58 post-Ⅰ.The results were found statistically significant(P【0.05,). Conclusions:This study suggests that histamine receptors play important roles in modulation of antibody generation in which H1R,H2R and H4R have immunosuppressive roles and conversely, H3R playes an immune enhancing role.The findings of this study may have clinical significance and provide the baseline information for future study.展开更多
The ventral pallidum(VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion.Although the VP receives afferent inputs from the central h...The ventral pallidum(VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion.Although the VP receives afferent inputs from the central histaminergic system, little is known about the effect of histamine on the VP and the underlying receptor mechanism. Here, we showed that histamine, a hypothalamicderived neuromodulator, directly depolarized and excited the GABAergic VP neurons which comprise a major cell type in the VP and are responsible for encoding cues of incentive salience and reward hedonics. Both postsynaptic histamine H1 and H2 receptors were found to be expressed in the GABAergic VP neurons and co-mediate the excitatory effect of histamine. These results suggested that the central histaminergic system may actively participate in VP-mediated motivational and emotional behaviors via direct modulation of the GABAergic VP neurons. Our findings also have implications for the role of histamine and the central histaminergic system in psychiatric disorders.展开更多
Epigenetic regulation has been attracting increasing attention due to its role in cell differentiation and behaviors.However,the epigenetic mechanisms that regulate human dendritic cell(DC)differentiation and developm...Epigenetic regulation has been attracting increasing attention due to its role in cell differentiation and behaviors.However,the epigenetic mechanisms that regulate human dendritic cell(DC)differentiation and development remain poorly understood.Our previous studies show that extracellular heat shock protein 70-like protein(HSP70L1)is a potent adjuvant of Th1 responses via stimulating DCs when released from cells;however,the role of intracellular HSP70L1 in DC differentiation and maturation remains unknown.Herein,we demonstrate that intracellular HSP70L1 inhibits human DC maturation by suppressing MHC and costimulatory molecule expression,in contrast to the adjuvant activity of extracellular HSP70L1.The stability of intracellular HSP70L1 is dependent on DNAJC2,a known epigenetic regulator.Mechanistically,intracellular HSP70L1 inhibits the recruitment of Ash1l to and maintains the repressive H3K27me3 and H2AK119Ub1 modifications on the promoter regions of costimulatory,MHC and STAT3 genes.Thus,intracellular HSP70L1 is an inhibitor of human DC maturation.Our results provide new insights into the epigenetic regulation of cell development by intracellular HSP70L1.展开更多
BACKGROUND: It has been demonstrated that histamine and its receptors in the hippocampus play an important role in memory and/or learning behaviors.OBJECTIVE: To investigate the expression levels of the histamine re...BACKGROUND: It has been demonstrated that histamine and its receptors in the hippocampus play an important role in memory and/or learning behaviors.OBJECTIVE: To investigate the expression levels of the histamine receptor gene and protein in the hippocampi of rats prior to and after administration of Trimeresurus albolabris venom using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot techniques. DESIGN, TIME AND SETTING: A controlled observation based on cellular protein level was performed in the College of Life Sciences, Chongqing Normal University between March 2005 and April 2007. MATERIALS: Eighty adult male Sprague-Dawley rats were provided by the Laboratory Animal Center of the Third Military Medical University of Chinese PLA. The lyophilized powder of Trimeresurus albolabris venom was collected from Jin-Hu-Shan in Chongqing, China. METHODS: Twenty rats were randomly and evenly divided into an experimental group and a control group The experimental group was subcutaneously injected with 0.65 mg/mL Trimeresurus albolabris venom, 0.5 mL for each rat. The control group was subcutaneously injected with an equal amount of 0.9% physiological saline. Prior to and after injection, rats from these two groups were placed in the Morris Water Maze for recording of path length and escape latency. The remaining 60 rats were randomly allocated to another experimental group (n = 50) and another control group (n = 10). Rats were correspondingly injected as described above. At different time points (0.1, 0.5, 1, 2, and 3 hours after injection), rats were decapitated and bilateral hippocampal tissues were dissociated (approximately 100 mg for each sample). Then, the acquired hippocampal tissue was immediately preserved at -70 ℃ for subsequent experiments. MAIN OUTCOME MEASURES: (1) The levels of histamine receptor (including H1R, H2R, and H3R) mRNA and protein in the hippocampi of rats were measured prior to and after injection of Trimeresurus albolabris venom using RT-PCR and Western Blot techniques. (2) Escape latency (namely, time to reach a platform) and path length were examined by Morris Water Maze testing. RESULTS: All 80 rats were included in the final analysis. In the experimental group, the level of mRNA for H3R receptor in rat hippocampi was just slightly changed, but the level of H3R receptor protein was significantly down-regulated compared with that in the control group (P 〈 0.05). Both mRNA and protein levels for H1R receptor were initially downregulated and then recovered to normal levels. Expression of H2R receptor mRNA was initially upregulated, then downregulated, and finally restored to the control level. The level of H2R receptor protein showed a tendency for downregulation. In the Morris Water Maze testing, escape latency and path length were significantly longer in the experimental group than in the control group (P 〈 0.05). CONCLUSION: Within three hours of injection with Trimeresurus albolabris venom, mRNA and protein levels of most histamine receptors in rat hippocampi were downregulated. Such changes possibly contribute to an impairment of memory and/or learning behaviors in rats following injection of Trimeresurus albolabris venom.展开更多
Objectives To investigate the expression of histamine H1 receptors (H1R) in the vestibular nucleus of brainstem in rats and the role of H1R in motion sickness (MS). Methods A total of 24 healthy Sprague-Dawley rat...Objectives To investigate the expression of histamine H1 receptors (H1R) in the vestibular nucleus of brainstem in rats and the role of H1R in motion sickness (MS). Methods A total of 24 healthy Sprague-Dawley rats were divided randomly into four groups (n=6 each) which determined if the animals would receive induction of MS or drug (promethazine) treatment: MS ( - )/Drug ( - ); MS(+)/Drug ( - ); MS ( - )/Drug ( + at 0.25 mg); and MS ( + )/ Drug(+). MS was induced by complex motion stimulation and the conditioned taste aversion was used as a behavioral indicator of MS. The volume of 0.15% sodium saccharin solution (SS) intake within 45 minutes after motion stimulation was measured. H1R in the vestibular nucleus was examined by immunofluorescence staining. The expression of H 1R protein in brainstem tissue at vestibular nucleus level was detected by western blot. Results The mean SS intake volume in the MS ( + )/Drug ( - ) group (8.8 ml) was significantly less than that of the MS ( - )/Drug ( - ) group (15.1 ml) (P 〈 0.01). The mean SS intake volume of the MS (-)/Drug (+) group (14.8 ml) was similar to that of the MS(-)/Drug(-) group. The mean SS intake volume (9.6 ml) of the MS(+)/Drug(+) group was more than that of the MS(+)/Drug(-)group (P〈0.01), but less than that of the MS(-)/Drug(-) group or MS(-)/Drug(+) group (P 〈 0.01). Immunofluorescence staining showed positive expression of H1R in the vestibular nucleus of brainstem and the expression was enhanced by motion stimulation. Western blot analysis showed that H1R protein expressed in the brainstem tissue at vestibular nucleus level and the expression also increased significantly after motion stimulation. The MS-induced increase of H1R was not affected significantly by promethazine. Conclusions H1Rs exist in the vestibular nucleus in rats and H 1R expression is up-regulated by motion stimulation, but not affected by promethazine. The findings indicate that the histaminergic system is involved in MS. Promethazine, as an H1R blocker, may play its anti-MS role by competing the binding site on H1Rs with histamine rather than inhibiting H1R expression.展开更多
Dear Editor,Influenza A viruses cause pandemics at an interval of approximately 10–40 years,and pigs are regarded as a'mixing vessel'because they are easily infected with avian and human influenza viruses(Ito...Dear Editor,Influenza A viruses cause pandemics at an interval of approximately 10–40 years,and pigs are regarded as a'mixing vessel'because they are easily infected with avian and human influenza viruses(Ito et al.,1998).According to previous studies,H3N2,H1N2,and展开更多
Objective To investigate the role of H1 and H2 receptors in the locus ceruleus (LC) in carotid sinus baroreceptor reflex (CSR) resetting induced by intracerebroventricular (i.c.v.) injection of histamine (HA)....Objective To investigate the role of H1 and H2 receptors in the locus ceruleus (LC) in carotid sinus baroreceptor reflex (CSR) resetting induced by intracerebroventricular (i.c.v.) injection of histamine (HA). Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner in vivo. ISP-mean arterial pressure (MAP) relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine (CHL) or cimetidine (CIM) into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA (100 ng in 5 μl) significantly shifted the ISP-MAP relationship curve upwards (P 〈 0.05) and obviously decreased the value of the reflex parameters such as MAP range and maximum gain (P 〈 0.05), but increased the threshold pressure, saturation pressure and ISP at maximum gain (P 〈 0.05). The pretreatment with CHL (0.5 μg in 1 μl) or CIM (1.5 μg in 1 μl) into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that of CHL (P 〈 0.05). Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly (P 〉 0.05). Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.展开更多
Objective Symptomatic predictors of influenza could assess risks and improve decisions about isolation and outpatient treatment. To develop such predictors, we undertook a prospective analysis of pandemic (HIN1) 200...Objective Symptomatic predictors of influenza could assess risks and improve decisions about isolation and outpatient treatment. To develop such predictors, we undertook a prospective analysis of pandemic (HIN1) 2009 and seasonal influenza (H3N2) in patients attending fever clinics. Methods From 1 May 2009 to 1 January 2010, all adult patients admitted to fever clinics for suspected influenza, confirmed by real time RT-PCR, were enrolled. Predictors of influenza virus infection were selected with logistic regression models. Measures of sensitivity, specificity, positive and negative likelihood ratios (LRs) were calculated to identify the best predictors. Results The clinical features and routine blood test results of influenza (H1N1) 2009 and seasonal influenza were similar. The positive and negative LRs of current US CDC influenza-like illness (ILl) criteria were modest in predicting influenza infection. Our modified clinic predictors improved the ability of the positive and negative LRs to recognize pandemic (HIN1) 2009 and seasonal influenza. The revised criteria are: fever ~ 38 ~C accompanied by at least one of the following--cough, arthralgia or relative iymphopenia. Conclusion Patients with symptoms and signs that meet the new criteria are likely to have influenza and timely antiviral therapy may be appropriate. In addition, physicians should ascertain if influenza is circulating within the community or if there is a contact history of influenza and combine this information with the newly developed criteria to clinically diagnose influenza.展开更多
RNA-directed DNA methylation(Rd DM) is a plant-specific de novo DNA methylation pathway,which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMO...RNA-directed DNA methylation(Rd DM) is a plant-specific de novo DNA methylation pathway,which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMOLOG 2(SHH2) is an H3 K9 me1 reader. Our structural studies reveal that H3 K9 me1 recognition is achieved by recognition of the methyl group via a classic aromatic cage and hydrogen-bonding and salt-bridge interactions with the free protons of the mono-methyllysine. The di-and tri-methylation states disrupt the polar interactions, decreasing the binding affinity. Our study reveals a monomethyllysine recognition mechanism which potentially links RdDM to H3 K9 me1 in maize.展开更多
基金National Natural Science Foundation of China(81973302)。
文摘OBJECTIVE Genetic variation in histamine H2 receptor(H2R)and H2R ligands are linked to schizophrenia,however little is known about how H2R contributes to pathogenesis of schizophrenia.Here,we detected a decreased expression of H2R in medial prefrontal cortex(mPFC)glutamatergic neurons in schizophrenia patients.METHODS AND RESULTS Selective knockout of H2R gene(Hrh2)in glutamatergic neurons induced schizophrenia-like behaviors including sensorimotor gating deficit,increased locomotor activity,social withdrawal and anhedo⁃nia in behavior tests,as well as reduced sponta⁃neous firing of mPFC glutamatergic neurons in electrophysiological tests.Selective deletion of the Hrh2 in mPFC glutamatergic neurons but not hippocampus glutamatergic neurons also induced such schizophrenia-like behaviors.Patch-clamp electrophysiology establishes that H2R deficiency reduced the intrinsic excitability of glutamatergic neurons by up-regulation of hyperpolarization activated cyclic nucleotide-gated channels.Fur⁃thermore,either overexpression of H2R in gluta⁃matergic neurons or activation of H2R in the mPFC reversed the MK-801-induced schizophrenia-like symptoms.CONCLUSION H2R can serve as a novel drug target given that functional deficiency of this receptor in mPFC glutamatergic neurons may be crucial for the pathogenesis of schizo⁃phrenia.H2R agonists can be viewed as drug candidates for the treatment of schizophrenia.
基金University Grants Commission, New Delhi,India for providing UGC Fellowship[UGC letter DON F.19-33/2006(CU)]Department of Science & Technology,Ministry of Science & Technology, Government of India for awarding "Young Scientist Project Award"(FT/SR-L-111/2006)
文摘Objective:To delineate the comparative immunomodulatory roles of H1R-H4R in antibody generation profile in rabbit model.Methods:The cohort comprised of eight groups containing 18(9 male and 9 female) rabbits in each group.GroupⅠremained non-immunized and received only vehicle(sterile distilled water,1 mL/kg×b.i.d.) intramuscularly.GroupⅡreceived vehicle (1 mL/kg×b.i.d.) while GroupsⅢ-Ⅶ(drugs-treated) received subcutaneous histamine (100μg/kg×b.i.d.),and intramuscular H1R-antagonist(pheniramine,10 mg/kg×b.i.d.), H2R-antagonist(ranitidine,10 mg/kg×b.i.d.),H3R-antagonist(iodophenpropit,1μg/kg×b.i.d.) and H4R-antagonist(JNJ 7777120,10μg/kg×b.i.d.),and GroupⅧDMSO(1 mL/kg×b.i.d.),respectively for 10 days(starting from day 1).They were subsequendy immunized with intravenous injection of sheep red blood cells(SRBC) at day 3.The estimation of serum Igs,IgM and IgG were done by ELISA,and observed at day 0(pre-immunization),and 7,14,21,28 and 58(post-immunization).Results:It was shown that histamine and HRs-antagonists could influence a detectable antibody response to SRBC as early as day 7-post-immunization(post-Ⅰ), which lasted until day 58 post-Ⅰ.The results were found statistically significant(P【0.05,). Conclusions:This study suggests that histamine receptors play important roles in modulation of antibody generation in which H1R,H2R and H4R have immunosuppressive roles and conversely, H3R playes an immune enhancing role.The findings of this study may have clinical significance and provide the baseline information for future study.
基金supported by the National Natural Science Foundation of China (81671107, 31330033, 91332124, 31471112, 31600834, and the NSFC and the Research Grants Council Joint Research Scheme 31461163001)the Ministry of Education of China (Fundamental Research Funds for the Central Universities 020814380071, 020814380048 and 020814380091)the China Postdoctoral Science Foundation (2017T100351)
文摘The ventral pallidum(VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion.Although the VP receives afferent inputs from the central histaminergic system, little is known about the effect of histamine on the VP and the underlying receptor mechanism. Here, we showed that histamine, a hypothalamicderived neuromodulator, directly depolarized and excited the GABAergic VP neurons which comprise a major cell type in the VP and are responsible for encoding cues of incentive salience and reward hedonics. Both postsynaptic histamine H1 and H2 receptors were found to be expressed in the GABAergic VP neurons and co-mediate the excitatory effect of histamine. These results suggested that the central histaminergic system may actively participate in VP-mediated motivational and emotional behaviors via direct modulation of the GABAergic VP neurons. Our findings also have implications for the role of histamine and the central histaminergic system in psychiatric disorders.
基金We thank Yanfeng Li for the technical assistance.This work was supported by grants from the National Key R&D Program of China(2018YFA0507401)the National Natural Science Foundation of China(31670875 and 31470858).
文摘Epigenetic regulation has been attracting increasing attention due to its role in cell differentiation and behaviors.However,the epigenetic mechanisms that regulate human dendritic cell(DC)differentiation and development remain poorly understood.Our previous studies show that extracellular heat shock protein 70-like protein(HSP70L1)is a potent adjuvant of Th1 responses via stimulating DCs when released from cells;however,the role of intracellular HSP70L1 in DC differentiation and maturation remains unknown.Herein,we demonstrate that intracellular HSP70L1 inhibits human DC maturation by suppressing MHC and costimulatory molecule expression,in contrast to the adjuvant activity of extracellular HSP70L1.The stability of intracellular HSP70L1 is dependent on DNAJC2,a known epigenetic regulator.Mechanistically,intracellular HSP70L1 inhibits the recruitment of Ash1l to and maintains the repressive H3K27me3 and H2AK119Ub1 modifications on the promoter regions of costimulatory,MHC and STAT3 genes.Thus,intracellular HSP70L1 is an inhibitor of human DC maturation.Our results provide new insights into the epigenetic regulation of cell development by intracellular HSP70L1.
文摘BACKGROUND: It has been demonstrated that histamine and its receptors in the hippocampus play an important role in memory and/or learning behaviors.OBJECTIVE: To investigate the expression levels of the histamine receptor gene and protein in the hippocampi of rats prior to and after administration of Trimeresurus albolabris venom using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot techniques. DESIGN, TIME AND SETTING: A controlled observation based on cellular protein level was performed in the College of Life Sciences, Chongqing Normal University between March 2005 and April 2007. MATERIALS: Eighty adult male Sprague-Dawley rats were provided by the Laboratory Animal Center of the Third Military Medical University of Chinese PLA. The lyophilized powder of Trimeresurus albolabris venom was collected from Jin-Hu-Shan in Chongqing, China. METHODS: Twenty rats were randomly and evenly divided into an experimental group and a control group The experimental group was subcutaneously injected with 0.65 mg/mL Trimeresurus albolabris venom, 0.5 mL for each rat. The control group was subcutaneously injected with an equal amount of 0.9% physiological saline. Prior to and after injection, rats from these two groups were placed in the Morris Water Maze for recording of path length and escape latency. The remaining 60 rats were randomly allocated to another experimental group (n = 50) and another control group (n = 10). Rats were correspondingly injected as described above. At different time points (0.1, 0.5, 1, 2, and 3 hours after injection), rats were decapitated and bilateral hippocampal tissues were dissociated (approximately 100 mg for each sample). Then, the acquired hippocampal tissue was immediately preserved at -70 ℃ for subsequent experiments. MAIN OUTCOME MEASURES: (1) The levels of histamine receptor (including H1R, H2R, and H3R) mRNA and protein in the hippocampi of rats were measured prior to and after injection of Trimeresurus albolabris venom using RT-PCR and Western Blot techniques. (2) Escape latency (namely, time to reach a platform) and path length were examined by Morris Water Maze testing. RESULTS: All 80 rats were included in the final analysis. In the experimental group, the level of mRNA for H3R receptor in rat hippocampi was just slightly changed, but the level of H3R receptor protein was significantly down-regulated compared with that in the control group (P 〈 0.05). Both mRNA and protein levels for H1R receptor were initially downregulated and then recovered to normal levels. Expression of H2R receptor mRNA was initially upregulated, then downregulated, and finally restored to the control level. The level of H2R receptor protein showed a tendency for downregulation. In the Morris Water Maze testing, escape latency and path length were significantly longer in the experimental group than in the control group (P 〈 0.05). CONCLUSION: Within three hours of injection with Trimeresurus albolabris venom, mRNA and protein levels of most histamine receptors in rat hippocampi were downregulated. Such changes possibly contribute to an impairment of memory and/or learning behaviors in rats following injection of Trimeresurus albolabris venom.
基金supported by The Eleventh Five-year Project of Chinese People's Liberation Army(Grant No.06MA023)
文摘Objectives To investigate the expression of histamine H1 receptors (H1R) in the vestibular nucleus of brainstem in rats and the role of H1R in motion sickness (MS). Methods A total of 24 healthy Sprague-Dawley rats were divided randomly into four groups (n=6 each) which determined if the animals would receive induction of MS or drug (promethazine) treatment: MS ( - )/Drug ( - ); MS(+)/Drug ( - ); MS ( - )/Drug ( + at 0.25 mg); and MS ( + )/ Drug(+). MS was induced by complex motion stimulation and the conditioned taste aversion was used as a behavioral indicator of MS. The volume of 0.15% sodium saccharin solution (SS) intake within 45 minutes after motion stimulation was measured. H1R in the vestibular nucleus was examined by immunofluorescence staining. The expression of H 1R protein in brainstem tissue at vestibular nucleus level was detected by western blot. Results The mean SS intake volume in the MS ( + )/Drug ( - ) group (8.8 ml) was significantly less than that of the MS ( - )/Drug ( - ) group (15.1 ml) (P 〈 0.01). The mean SS intake volume of the MS (-)/Drug (+) group (14.8 ml) was similar to that of the MS(-)/Drug(-) group. The mean SS intake volume (9.6 ml) of the MS(+)/Drug(+) group was more than that of the MS(+)/Drug(-)group (P〈0.01), but less than that of the MS(-)/Drug(-) group or MS(-)/Drug(+) group (P 〈 0.01). Immunofluorescence staining showed positive expression of H1R in the vestibular nucleus of brainstem and the expression was enhanced by motion stimulation. Western blot analysis showed that H1R protein expressed in the brainstem tissue at vestibular nucleus level and the expression also increased significantly after motion stimulation. The MS-induced increase of H1R was not affected significantly by promethazine. Conclusions H1Rs exist in the vestibular nucleus in rats and H 1R expression is up-regulated by motion stimulation, but not affected by promethazine. The findings indicate that the histaminergic system is involved in MS. Promethazine, as an H1R blocker, may play its anti-MS role by competing the binding site on H1Rs with histamine rather than inhibiting H1R expression.
基金in part funded by a 2015 research fund from Chungnam National University
文摘Dear Editor,Influenza A viruses cause pandemics at an interval of approximately 10–40 years,and pigs are regarded as a'mixing vessel'because they are easily infected with avian and human influenza viruses(Ito et al.,1998).According to previous studies,H3N2,H1N2,and
文摘Objective To investigate the role of H1 and H2 receptors in the locus ceruleus (LC) in carotid sinus baroreceptor reflex (CSR) resetting induced by intracerebroventricular (i.c.v.) injection of histamine (HA). Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner in vivo. ISP-mean arterial pressure (MAP) relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine (CHL) or cimetidine (CIM) into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA (100 ng in 5 μl) significantly shifted the ISP-MAP relationship curve upwards (P 〈 0.05) and obviously decreased the value of the reflex parameters such as MAP range and maximum gain (P 〈 0.05), but increased the threshold pressure, saturation pressure and ISP at maximum gain (P 〈 0.05). The pretreatment with CHL (0.5 μg in 1 μl) or CIM (1.5 μg in 1 μl) into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that of CHL (P 〈 0.05). Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly (P 〉 0.05). Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.
基金supported by Chinese National Programs for High Technology Research and Development (863 Program,2008AA02Z416)
文摘Objective Symptomatic predictors of influenza could assess risks and improve decisions about isolation and outpatient treatment. To develop such predictors, we undertook a prospective analysis of pandemic (HIN1) 2009 and seasonal influenza (H3N2) in patients attending fever clinics. Methods From 1 May 2009 to 1 January 2010, all adult patients admitted to fever clinics for suspected influenza, confirmed by real time RT-PCR, were enrolled. Predictors of influenza virus infection were selected with logistic regression models. Measures of sensitivity, specificity, positive and negative likelihood ratios (LRs) were calculated to identify the best predictors. Results The clinical features and routine blood test results of influenza (H1N1) 2009 and seasonal influenza were similar. The positive and negative LRs of current US CDC influenza-like illness (ILl) criteria were modest in predicting influenza infection. Our modified clinic predictors improved the ability of the positive and negative LRs to recognize pandemic (HIN1) 2009 and seasonal influenza. The revised criteria are: fever ~ 38 ~C accompanied by at least one of the following--cough, arthralgia or relative iymphopenia. Conclusion Patients with symptoms and signs that meet the new criteria are likely to have influenza and timely antiviral therapy may be appropriate. In addition, physicians should ascertain if influenza is circulating within the community or if there is a contact history of influenza and combine this information with the newly developed criteria to clinically diagnose influenza.
基金supported by National Natural Science Foundation of China(31770782)the Ministry of Science and Technology of China(2016YFA0503200)+1 种基金the Shenzhen Science and Technology Program(JCYJ20200109110403829 and KQTD20190929173906742)Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes(2019KSYS006)to J.D.
文摘RNA-directed DNA methylation(Rd DM) is a plant-specific de novo DNA methylation pathway,which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMOLOG 2(SHH2) is an H3 K9 me1 reader. Our structural studies reveal that H3 K9 me1 recognition is achieved by recognition of the methyl group via a classic aromatic cage and hydrogen-bonding and salt-bridge interactions with the free protons of the mono-methyllysine. The di-and tri-methylation states disrupt the polar interactions, decreasing the binding affinity. Our study reveals a monomethyllysine recognition mechanism which potentially links RdDM to H3 K9 me1 in maize.