Objective: To explore the effect of high dose of glucocorticoid (GC) on the synthesis of corticotropin releasing hormone (CRH) and transcription of its mRNA in hypothalamus paraventricular nuclei (PVN) in order...Objective: To explore the effect of high dose of glucocorticoid (GC) on the synthesis of corticotropin releasing hormone (CRH) and transcription of its mRNA in hypothalamus paraventricular nuclei (PVN) in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods: A total of 60 rats were divided into 5 groups: blank control, 10^-6 mol/L dexamethasone (DEX) group, 10^-9 mol/L DEX group, 0.9% saline group and GR blocking group (10^-2mol/L RU486). All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy (LCSM); CRH mRNA level was explored by in situ hybridization. Results: 10^-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion : High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.展开更多
Objective: To study the effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia. Methods: a total of 80 patients with ...Objective: To study the effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia. Methods: a total of 80 patients with severe pneumonia who were hospitalized between August 2014 and January 2017 were retrospectively analyzed and divided into the routine treatment group (n=46) who received conventional antibiotic therapy and the combined treatment group (n=34) who received glucocorticoid combined with antibiotic therapy, and the differences in infection indexes, acute proteins and stress hormones were compared between the two groups of patients before and after treatment. Results: The differences in serum levels of infection indexes, acute phase proteins and stress hormones were not statistically significant between the two groups before treatment. After 1 week of treatment, serum infection indexes CRP and PCT levels of observation group were lower than those of control group;serum acute phase proteins α1-AT, α1-AG and CER levels were lower than those of control group;serum stress hormones Cor, AngⅠ and AngⅡ levels were lower than those of control group. Conclusion:Glucocorticoid combined with antibiotics can effectively inhibit systemic infection and stress and optimize the illness in patients with severe pneumonia.展开更多
Glucocorticoids(GCs) are a group of endocrine-disrupting compounds(EDCs) frequently prescribed against various medical conditions.Recently,GCs have been shown to be effective in managing septic shock in patients infec...Glucocorticoids(GCs) are a group of endocrine-disrupting compounds(EDCs) frequently prescribed against various medical conditions.Recently,GCs have been shown to be effective in managing septic shock in patients infected with the 2019 novel coronavirus(COVID-19).Due to colossal consumption and potential risks to aquatic organisms,GCs have immensely attracted the focus of the scientific research community as a water pollutant.Therefore,the aim of this paper is to review the current knowledge on the occurrence of various GCs in the aquatic environment and their removal during wastewater treatment.A variety of GCs are ubiquitous in surface water,hospital wastewater,and sewage water worldwide.And the minimum concentration in volume is below 0.01 ng/L,and the maximum one is 10 000 ng/L,and enter the environment through hospital and urban wastewater discharging.Compared with natural GCs,higher risks to aquatic environments could be induced by synthetic GCs.The current activated sludge processes used in wastewater treatment plants(WWTPs) are not fully effective in eliminating GCs,some of which may further increase the risk of GC in the environment.In comparison with the aerobic process in WWTPs,the anaerobic and anoxic processes were found to be more efficient for GC degradation.Of the studied GCs,fluticasone propionate,clobetasol propionate,fluocinolone acetonide,and triamcinolone acetonide need more attention due to their low removal efficiencies and strong toxicity.Among the advanced treatment processes,reverse osmosis,ultraviolet irradiation,CaO_(2),and plasma could achieve significant GC activity removal while micro/ultra-filtration,chlorination,and ozonation were less efficient.展开更多
BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE...BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS: A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups (n = 45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed (P 〈 0.05-0.01). CONCLUSION: Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.展开更多
Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS)...Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).展开更多
It is increasingly recognized that asthma represents a syndrome, and there is clinical and pathobiological heterogeneity. Many genes are reported to be associated with asthma, and may be involved in the disease hetero...It is increasingly recognized that asthma represents a syndrome, and there is clinical and pathobiological heterogeneity. Many genes are reported to be associated with asthma, and may be involved in the disease heterogeneity. Diverse cells, such as T helper 1 (Th1)-cells, Th2-cells, Th17-cells, airway epithelial cells, and innate and adaptive immunity associated cells, contribute to the pathobiology of asthma independently of each other or they can also coexist and interact. Although, generally, Th2 immunity is important in most asthma endotypes, non- Th2-driven inflammation tends to be difficult to manage. Recently, increased attention has been focused on severe asthma and glucocorticoid (GC)-resistant (GC-R) asthma, in which diverse inflammatory processes may be involved. Treatment approaches should take into account pathological differences.展开更多
Objective: To evaluate the effects of thyorotropin-releasing hormone (TRH ) on severe head injury.Methods: Eighty--seven severely head injured patients with a Glasgow Coma Scale (GCS ) score of & or less wererando...Objective: To evaluate the effects of thyorotropin-releasing hormone (TRH ) on severe head injury.Methods: Eighty--seven severely head injured patients with a Glasgow Coma Scale (GCS ) score of & or less wererandomized into TRH--treated and saline control groups. In TRH treated group. the treatment was started with abolus injection of 0. 2 mg/kg followed by continuous infusion for 2 hours at 0. 2 mg/kg/h. Such treatment wasgiven once a day for 4 times. The patients in control group were given the equivalent normal saline with the samemethod. Results: TRH, administered intravenously after head injury. promoted the recovery of consciousness andGCS score, alleviated the traumatic brain edema, controlled and lowered the intracranial pressure. decreased thelevel of lipid superoxides, decreased the mortality rate. and improved the life quality of the survivals. Nocomplications or adverse and toxic effects were noted during the course of TRH treatment. Conclusion: TRH hasbeneficial effects on patients with severe head injury.展开更多
目的:探讨褪黑素(MLT)对足部电击所致创伤后应激障碍(PTSD)大鼠下丘脑-垂体-肾上腺(HPA)轴的影响。方法:利用足底电击法制备大鼠PTSD模型,通过腹腔注射方法给予治疗组大鼠MLT。通过拒俘反应测试检测大鼠的行为学变化,利用real time RT-...目的:探讨褪黑素(MLT)对足部电击所致创伤后应激障碍(PTSD)大鼠下丘脑-垂体-肾上腺(HPA)轴的影响。方法:利用足底电击法制备大鼠PTSD模型,通过腹腔注射方法给予治疗组大鼠MLT。通过拒俘反应测试检测大鼠的行为学变化,利用real time RT-PCR方法检测下丘脑中促肾上腺皮质激素释放激素(CRH)mRNA的表达,利用酶联免疫吸附试验(ELISA)检测血清中促肾上腺皮质激素(ACTH)、肾上腺素(EPI)和糖皮质激素(GC)的含量。结果:PTSD组大鼠拒俘反应明显(P<0.05),下丘脑中CRH mRNA表达升高(P<0.05),血清中ACTH和EPI明显升高(P<0.05),但是GC水平下降(P<0.05)。MLT治疗后可以明显缓解PTSD大鼠拒俘反应(P<0.05),同时降低下丘脑中CRH mRNA表达(P<0.05),降低血清中ACTH和EPI水平并升高GC的水平(P<0.05)。结论:MLT治疗可缓解PTSD大鼠的症状,并恢复HPA轴的神经内分泌平衡。展开更多
文摘Objective: To explore the effect of high dose of glucocorticoid (GC) on the synthesis of corticotropin releasing hormone (CRH) and transcription of its mRNA in hypothalamus paraventricular nuclei (PVN) in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods: A total of 60 rats were divided into 5 groups: blank control, 10^-6 mol/L dexamethasone (DEX) group, 10^-9 mol/L DEX group, 0.9% saline group and GR blocking group (10^-2mol/L RU486). All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy (LCSM); CRH mRNA level was explored by in situ hybridization. Results: 10^-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion : High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.
文摘Objective: To study the effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia. Methods: a total of 80 patients with severe pneumonia who were hospitalized between August 2014 and January 2017 were retrospectively analyzed and divided into the routine treatment group (n=46) who received conventional antibiotic therapy and the combined treatment group (n=34) who received glucocorticoid combined with antibiotic therapy, and the differences in infection indexes, acute proteins and stress hormones were compared between the two groups of patients before and after treatment. Results: The differences in serum levels of infection indexes, acute phase proteins and stress hormones were not statistically significant between the two groups before treatment. After 1 week of treatment, serum infection indexes CRP and PCT levels of observation group were lower than those of control group;serum acute phase proteins α1-AT, α1-AG and CER levels were lower than those of control group;serum stress hormones Cor, AngⅠ and AngⅡ levels were lower than those of control group. Conclusion:Glucocorticoid combined with antibiotics can effectively inhibit systemic infection and stress and optimize the illness in patients with severe pneumonia.
基金National Natural Science Foundation of China (No. 52270062)Natural Science Foundation of Shanghai,China (No. 22ZR1402800)+1 种基金Shanghai Rising-Star Program,China (No. 23QC1400800)Shenzhen Science and Technology Program,China (No. JSGG20220606141402005)。
文摘Glucocorticoids(GCs) are a group of endocrine-disrupting compounds(EDCs) frequently prescribed against various medical conditions.Recently,GCs have been shown to be effective in managing septic shock in patients infected with the 2019 novel coronavirus(COVID-19).Due to colossal consumption and potential risks to aquatic organisms,GCs have immensely attracted the focus of the scientific research community as a water pollutant.Therefore,the aim of this paper is to review the current knowledge on the occurrence of various GCs in the aquatic environment and their removal during wastewater treatment.A variety of GCs are ubiquitous in surface water,hospital wastewater,and sewage water worldwide.And the minimum concentration in volume is below 0.01 ng/L,and the maximum one is 10 000 ng/L,and enter the environment through hospital and urban wastewater discharging.Compared with natural GCs,higher risks to aquatic environments could be induced by synthetic GCs.The current activated sludge processes used in wastewater treatment plants(WWTPs) are not fully effective in eliminating GCs,some of which may further increase the risk of GC in the environment.In comparison with the aerobic process in WWTPs,the anaerobic and anoxic processes were found to be more efficient for GC degradation.Of the studied GCs,fluticasone propionate,clobetasol propionate,fluocinolone acetonide,and triamcinolone acetonide need more attention due to their low removal efficiencies and strong toxicity.Among the advanced treatment processes,reverse osmosis,ultraviolet irradiation,CaO_(2),and plasma could achieve significant GC activity removal while micro/ultra-filtration,chlorination,and ozonation were less efficient.
基金the Postdoctoral Science Foundation of China,No. 20060390301the National Natural Science Foundation of China,No.30600341the Ph.D.Program Foundation of Ministry of Education of China,No.20050159011
文摘BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS: A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups (n = 45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed (P 〈 0.05-0.01). CONCLUSION: Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.
基金Supported by Research Grants for Nervous and Mental Disorders from the Ministry of Health,Labor and Welfare Health and Labor Sciences Research Grants (Research on Psychiatric and Neurological Diseases and Mental Health)+2 种基金Health and Labor Sciences Research Grants,a grant from the Japan Foundation for Neuroscience and Mental Healththe Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (Kunugi H)a Grant-in-Aid for Young Scientists (A) (21680034) from the Ministry of Education,Culture,Sports,Science,and Technology of Japan (Numakawa T)
文摘Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).
文摘It is increasingly recognized that asthma represents a syndrome, and there is clinical and pathobiological heterogeneity. Many genes are reported to be associated with asthma, and may be involved in the disease heterogeneity. Diverse cells, such as T helper 1 (Th1)-cells, Th2-cells, Th17-cells, airway epithelial cells, and innate and adaptive immunity associated cells, contribute to the pathobiology of asthma independently of each other or they can also coexist and interact. Although, generally, Th2 immunity is important in most asthma endotypes, non- Th2-driven inflammation tends to be difficult to manage. Recently, increased attention has been focused on severe asthma and glucocorticoid (GC)-resistant (GC-R) asthma, in which diverse inflammatory processes may be involved. Treatment approaches should take into account pathological differences.
文摘Objective: To evaluate the effects of thyorotropin-releasing hormone (TRH ) on severe head injury.Methods: Eighty--seven severely head injured patients with a Glasgow Coma Scale (GCS ) score of & or less wererandomized into TRH--treated and saline control groups. In TRH treated group. the treatment was started with abolus injection of 0. 2 mg/kg followed by continuous infusion for 2 hours at 0. 2 mg/kg/h. Such treatment wasgiven once a day for 4 times. The patients in control group were given the equivalent normal saline with the samemethod. Results: TRH, administered intravenously after head injury. promoted the recovery of consciousness andGCS score, alleviated the traumatic brain edema, controlled and lowered the intracranial pressure. decreased thelevel of lipid superoxides, decreased the mortality rate. and improved the life quality of the survivals. Nocomplications or adverse and toxic effects were noted during the course of TRH treatment. Conclusion: TRH hasbeneficial effects on patients with severe head injury.
文摘目的:探讨褪黑素(MLT)对足部电击所致创伤后应激障碍(PTSD)大鼠下丘脑-垂体-肾上腺(HPA)轴的影响。方法:利用足底电击法制备大鼠PTSD模型,通过腹腔注射方法给予治疗组大鼠MLT。通过拒俘反应测试检测大鼠的行为学变化,利用real time RT-PCR方法检测下丘脑中促肾上腺皮质激素释放激素(CRH)mRNA的表达,利用酶联免疫吸附试验(ELISA)检测血清中促肾上腺皮质激素(ACTH)、肾上腺素(EPI)和糖皮质激素(GC)的含量。结果:PTSD组大鼠拒俘反应明显(P<0.05),下丘脑中CRH mRNA表达升高(P<0.05),血清中ACTH和EPI明显升高(P<0.05),但是GC水平下降(P<0.05)。MLT治疗后可以明显缓解PTSD大鼠拒俘反应(P<0.05),同时降低下丘脑中CRH mRNA表达(P<0.05),降低血清中ACTH和EPI水平并升高GC的水平(P<0.05)。结论:MLT治疗可缓解PTSD大鼠的症状,并恢复HPA轴的神经内分泌平衡。