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[Abstract] Objective To elucidate the important role of Nogo-A in climacteric neurodegeneration such as memory impairment by observing memory function and the expression of Nogo-A in hippocampus and striatum of rats under low estrogen condition. Methods Fouthy-five female SD rats were divided into sham operation group, ovariectomized group and ovariectomized estrogen treatment group with 15 rats in each group. Medication was given 2 weeks after ovariectomized. Estrogen treatment group was subcutaneously injected in groin with estrogen [25 μg/ (kg.d)] dissolved in sterile sesame oil. The sham operation group and the ovariectomized group were given the same amount of aseptic sesame oil. Samples were collected after 6 weeks of drug treatment. The difference of memory function of rats in three groups was observed by conditioned fear training experiment, and the expression of Nogo-A in hippocampus and striatum was observed by immunohistochemistry and Western blotting. Results Compared with the sham and estrogen treatment group, memory function in ovariectomized group decreased significantly and the number of Nogo-A positive neurons in hippocampus and striatum of ovariectomized rats was significantly higher than that of sham operation group (P 0. 05). The result of immunoblotting was consistent with the above-mentioned immunohistochemical result. Conclusion The increased expression of Nogo-A in hippocampus and striatum under low estrogen condition may be one of the key reasons for memory impairment in climacteric women.
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Nogo protein is the fourth member of reticulin famity. Nogo mRNA produced by encoding gene transcription, forms three different RNA transcripts due to different promoter and splicing modes, namely Nogo-A, Nogo-B and Nogo-C protein. Nogo protein was first found in the central nervous system, and then proved to be widely expressed in peripheral tissues such as heart, liver and vascular endothelium. Studies have shown that Nogo protein can participate in the regulation of myocardial fibrosis through RhoA/Rho-associated kinase(ROCK) pathway, endoplasmic reticulum stress, Sce61 a and other signaling pathways. In this paper, the relationship between Nogo-A, Nogo-B, Nogo-C and myocardial fibrosis is briefly introduced.
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As bioactive lipids, sphingolipids participate in the signal transduction of many important physiological processes such as growth and apoptosis. Besides, abnormal levels of sphingolipids were detected in a variety of clinical conditions including hypertension and coronary heart disease, suggesting that sphingolipid metabolism is involved in the occurrence and development of cardiovascular diseases. This paper reviewed the relationship between sphingolipid metabolism with four common cardiovascular diseases, coronary heart disease, hypertension, arrhythmia and heart failure, and the mechanisms involved. What's more, the prospect of sphingolipid pathway as a potential target for the diagnosis and treatment of cardiovascular diseases is put forward.
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Nogo-B is a major family member of the reticulon protein family 4. It is widely expressed in the central nervous system and peripheral tissues. Studies have shown that Nogo-B binds to three different receptors; Nogo receptor-1 (NgRl), Nogo-B specific receptor (NgBR) and paired immunoglobulin like receptor B(PirB). These receptors play a dual role of suppression and promotion in angiogenesis, proliferation and apoptosis, invasion and migration, which are important events in tumor development and progression, through various post-receptor signaling pathways, including RhoA/Rho- associated coiled-coil contaning protein kinase (RhoA/ROCK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/ Akt), adenosine 5-monophosphate-activated protein kinase α/liver X receptor α(AMPAa/LXRα), extracellular signal- regulated kinase (ERK), epithelial-mesenchymal transition (EMT), unfolded protein response (UPR) and so on. An in- depth understanding of the mechanisms by which Nogo-B receptors are involved in tumor pathogenesis will provide new insights into the development of drugs. Here, we will summarize the up-to-date researches on the basic structure and expression of Nogo-B/Nogo-B receptors and the suppressing/activating effects of post-receptor signaling pathways in the pathogenesis of malignant solid tumors.
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AIM:To investigate the effects of Jiawei-Naotai formula (JWNTF) on ATF4/CHOP/Puma pathway in hippocampal neurons of ovariectomized female rats with cerebral ischemia.METHODS:The female rats were randomly divided into sham group, model group, JWNTF group and positive control group.The rats, expect in the sham group, were ovariectomized.The rats in each group were intragastric administration 11 days after ovariectomy.The rats in sham group and model group were given a gavage of 0.9％Na Cl, while the rats in other groups were administrated by corresponding therapy intragastrically for 3 d.The regional cerebral ischemia model was established by middle cerebral artery occlusion (MCAO) suture method 14 days after ovariectomy.The behaviors of the rats were evaluated 24 h after cerebral ischemia.The mRNA levels of Bax, Bcl-2 and caspase-3 were detected by RT-qPCR, and the protein expression of Bax, Bcl-2, caspase-3, ATF4, CHOP and Puma was determined by Western blot.RESULTS:Compared with sham group, the neurobehavioral scores significantly increased in other groups (P<0.05).Compared with model group, the neurobehavioral scores were significantly decreased in positive control group and JWNTF group (P<0.05).The protein expression of Bax, caspase-3, ATF4, CHOP and Puma, and the mRNA expression of Bax and caspase-3 in the hippocampus were much higher, and Bcl-2 was lower in model group than those in sham group (P<0.05).JWNTF significantly reduced the protein expression of Bax, caspase-3, ATF4 and CHOP, and the mRNA expression of Puma, Bax and caspase-3, and markedly increased the expression of Bcl-2 at mRNA and protein levels compared with model group.CONCLUSION:The JWNTF protects against brain damage induced by cerebral ischemia, which may be related to inhibitiing the expression of ATF4/CHOP/Puma pathway-related molecules at mRNA and protein levels.
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Objective The occurrence of perimenopausal hot flashes involves many theories, among which the study of neurotransmitter mechanism has attracted much attention. This study aims to investigate the changes of α1 and α2 adrenoreceptors in the preoptic area of the hypothalamus(POAH) in ovariectomized rats after 4 weeks treatment with estradiol valerate, and explore the potential neurotransmitter mechanism of perimenopausal hot flashes. Methods 30 female Sprague-Dawley rats, weighing 230±10 g and aged 6-8WK, were divided into three groups: ovariectomy (OVX)group , sham group, and ovariectomy plus estradiol valerate (OVX+E2) group, each 10. Rats in sham-operated group opened pelvic cavity to find ovaries, but did not remove them. The other rats underwent bilateral ovariectomy under sterile conditions. Rats in OVX group and (OVX+E2) group received bilateral ovariectomy, rats in OVX group received isotonic saline gavage (10 mg/kg), and rats in (OVX+E2) group received estradiol valerate gavage (0.8 mg /kg). Anesthesia, cardiac perfusion and paraffin section were made after taking the brain. The expression of α1 and α2 adrenoreceptors in POAH of the rats was detected by immunohistochemistry. Results After 4 weeks’ treatment, the number of α1[(54.0±3.9)/100μm2] and α2[(89.0±2.4)/100μm2] adrenoreceptor positive cells in POAH of OVX group significantly decreased compared with that in sham group[(66.3±4.0)、(71.0±2.2)/100μm2](P<0.01),while the number of α1 and α2 [(63.7±4.5)、(73.1±3.5)/100μm2)] adrenoreceptor positive cells in POAH of（OVX+E2 ）group significantly increased compared with that in OVX group(P<0.01). The difference was statistically significant. Conclusion The expression of two adrenergic receptors in the POAH of ovariectomized rats changed. The central noradrenergic system may be involved in the mechanism of perimenopausal hot flashes,which need further studying.
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Objective To investigate the effect of Jiawei Naotaifang on neuronal apoptosis and the mechanism in ovariectomized rats with cerebral ischemia. Methods Female Sprague-Dawley rats(n=40)were randomly divided into sham group(n=10),model group(n=10),es-trogen group(n=10)and Jiawei Naotaifang group(n=10).The model group,estrogen group and Jiawei Naotai-fang group were ovariectomized.Eleven days after ovariectomy,the estrogen group and Jiawei Naotaifang group were given estrogen and Jiawei Naotaifang respectively intragastrically for three days.14 days after ovariecto-my,the model group,estrogen group and Jiawei Naotaifang group were modeled cerebral ischemia with Langa's method.24 hours after modeling,the apoptosis rate of neurons was detected with TUNEL,and the activation of extracellular signal-regulated kinase 1/2(ERK1/2)and c-Jun N-terminal kinase(p-JNK)in hippocampus were de-tected with Western blotting. Results Compared with the model group, the apoptosis rates decreased in Jiawei Naotaifang group and the estrogen group(P<0.001),with more activation of ERK1/2(P<0.01)and less activation of JNK(P<0.01). Conclusion Jiawei Naotaifang can protect neuron from apoptosis by promoting the activation of ERK1/2 and inhibiting the activation of p-JNK.
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Aim To investigate the effects of Jiawei Naotaifang on cerebral infarction area, pathological changes of brain tissue and estrogen level of focal cere-bral Iischemia in female ovariectomized rats, and cor-relation between estrogen levels and cerebral infarction area. Methods SD rats were randomly divided into sham operation group, ovariectomized group, cerebral ischemia group,model group,and drug groups(estro-gen group, Jiawei Naotaifang high dose group, Jiawei Naotaifang middle dose group, Jiawei Naotaifang low dose group). The rats in the ovariectomized group, model group, drug groups were ovariectomized, elev-enth days after the ovariectomy. The rats in the drug groups were given intragastric administration for three days. The rats in the model group, cerebral ischemia group and drug groups were prepared for cerebral is-chemia models. Neurological function scores were scored 24 hours after the success of the model, serum levels of estrogen were detected, and the brain was stained with 2, 3, 5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin staining(HE), TTC staining was used to measure the area of cerebral in-farction, and HE staining was used to observe the pathological changes of brain tissues. Results Com-pared with cerebral ischemia group,cerebral infarction area of rats in the model group increased significantly, the estrogen level was lower and the necrosis and py-knosis of cortical and hippocampus cells of rats in the model group were more obvious. Compared with model group,the cerebral infarction area of rats in the drug groups was reduced,the estrogen levels were elevated, especially in Jiawei Naotaifang high dose group and es-trogen group. The cell morphology of rats,in the estro-gen group,Jiawei Naotaifang high dose group and mid-dle dose group, was improved obviously. Cerebral in-farction area was negatively correlated with the level of estrogen. Conclusions The cerebral infarction area of cerebral ischemia in female ovariectomized rat is signif-icantly correlated with the level of estrogen. Jiawei Naotaifang can reduce the damage and alleviate brain injury of cerebral ischemia in female ovariectomized rats,which may be related to the improvement of estro-gen level.
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OBJECTIVE@#To explore the significance of osteopontin and nuclear factor κB (NF-κB) expression in patients with knee osteoarthritis.@*METHODS@#RT-PCR and enzyme-linked immunosorbent assay were used to measure the Osteopontin (OPN) and NF-κB concentration of knee joint synovial fluid of patients with knee osteoarthritis and trauma fractures, and analyze the relationship between the expressiones of them.@*RESULTS@#OPN and NF-κB expression at the mRNA and protein levels of patients with knee osteoarthritis were significantly higher than the control group. the result showed statistical significance (P<0.05). There was a positive correlation between the OPN levels in synovial fluid of patients with knee osteoarthritis and NF-κB expression levels (P<0.05).@*CONCLUSIONS@#The high expression of OPN and NF-κB are closely related to occurrence and development of knee osteoarthritis.
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Adult , Aged , Female , Humans , Male , Middle Aged , Blotting, Western , Case-Control Studies , NF-kappa B , Genetics , Metabolism , Osteoarthritis, Knee , Metabolism , Osteopontin , Genetics , Metabolism , Polymerase Chain Reaction , RNA, Messenger , Genetics , Metabolism , Statistics, Nonparametric , Synovial Fluid , MetabolismABSTRACT
<p><b>BACKGROUND</b>The mechanism of cerebral vasospasm following subarachnoid haemorrhage (SAH) is not understood. Here, we hypothesized that apoptosis of endothelial cells induced by p53 and its target gene em dash p53 upregulated modulator of apoptosis (PUMA) played an important role in development of cerebral vasospasm. We also observed the effects of a p53 inhibitor, pifithrin-alpha (PFT-alpha), on reducing the expression of p53 and PUMA, consequently decreasing the apoptosis of endothelial cells and alleviating cerebral vasospasm.</p><p><b>METHODS</b>Male Sprague-Dawley rats weighing 300-350 g were randomly divided into five groups: a control group (sham surgery), a SAH group, a SAH+dimethyl sulfoxide (DMSO) group, a SAH + PFT-alpha (0.2 mg/kg) group and a SAH + PFT-alpha (2.0 mg/kg) group. PFT-alpha was injected intraperitoneally immediately after SAH. Rats were sacrificed 24 hours after SAH. Western blot and immunohistochemical staining were used to detect the levels of p53, PUMA and caspase-3 protein. In addition, mortality and neurological scores were assessed for each group. Statistical significance was assured by analysis of variance performed in one way ANOVA followed by the Tukey test. The neurological and mortality scores were analyzed by Dunn's method and Fisher exact test, respectively.</p><p><b>RESULTS</b>After SAH, Western blot and immunohistochemical staining showed the levels of p53, PUMA and caspase-3 in the endothelial cells and the numbers of TdT mediated dUTP nick end labelling (TUNEL) positive endothelial cells were all significantly increased in the basilar arteries (P<0.05), but significantly reduced by PFT-alpha (P<0.05). These changes were accompanied by increasing diameters and declining wall thickness of basilar arteries (P<0.05), as well as reduced mortality and neurological deficits of the rats (P<0.05).</p><p><b>CONCLUSIONS</b>PFT-alpha could protect cerebral vessels from development of vasospasm and improve neurological outcome as well as reduce the mortality via suppressing apoptosis induced by p53 in the endothelial cells of cerebral vessels.</p>