Effects of Shikonin on the Bone Microenvironment and Heterogeneity of Spinal Tumor Cells by Regulating the High Mobility Group Protein B1-Toll Like Receptor 4-Nuclear Factor Kappa-B Signaling Pathway

2019 ◽  
Vol 9 (11) ◽  
pp. 1595-1599
Author(s):  
Bo Chen ◽  
Bo Liu ◽  
Feng-Feng Nie ◽  
Zai-Qing Zhang ◽  
Fa-Qing Wan
Keyword(s):  
Signaling Pathway ◽  
Tumor Cells ◽  
Spinal Tumor ◽  
Spinal Tumors ◽  
Sham Operation ◽  
Bone Microenvironment ◽  
Model Group ◽  
Sham Operation Group ◽  
Tlr4 Mrna ◽  
Operation Group

Aim: The present study was conducted with an attempt to evaluate the potential therapeutic effect of shikonin on spinal tumors in vivo and its mechanism. Methods: The morphology of rat spinal tumor was observed by H&E staining, and apoptosis of rat spinal tumor was detected by transfection method and TUNEL method. In addition, the expression of cytokine mRNA and related proteins in spinal tumors of rats were detected by real-time PCR and Western blotting assays. Results: At the same period, the BBB score in the model group was significantly lower than that in the sham operation group and the shikonin group (P < 0.05). Compared with the sham operation group, the BBB score in the shikonin group was significantly lower than that in the sham operation group (P < 0.05), but significantly higher than that in the model group (P < 0.05). Based on the RT-PCR results, the level of HMGB1 mRNA in the shikonin group was significantly lower than that of the model group (P < 0.05), and the level of TLR4 mRNA in the model group was significantly lower than that in the model group (P < 0.05). Moreover, the NF-κB mRNA level in the shikonin group was significantly lower than that in the model group (P < 0.05). The expression level of HMGB1, TLR4 and NF- B in the shikonin group was significantly lower than that in the model group (P < 0.05). Together, the results revealed that shikonin reduced the expression of HMGB1, TLR4 and NF-κB mRNA and protein. The apoptosis rate of tumor cells in the shikonin group was significantly higher than that in the model group (P < 0.05). The expression of caspase-3 in the shikonin group was significantly higher than that in the model group, which further indicated that shikonin could promote apoptosis of spinal tumor cells in rats. Conclusion : Shikonin has the potential to affect the heterogeneity of the bone microenvironment and spinal tumor cells by regulating the HMGB1-TLR4-NF-κB signaling pathway.

scholarly journals The effect of lithium chloride on the motor function of spinal cord injury–controlled rat and the relevant mechanism

2019 ◽  
Vol 17 ◽  
pp. 205873921985285
Author(s):  
Gang Chen ◽  
Yimin Liang ◽  
Fanghu Chen ◽  
Haifeng Wang ◽  
Guoming Zhu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lithium Chloride ◽  
Sham Operation ◽  
Model Group ◽  
Nissl Staining ◽  
Sham Operation Group ◽  
Significant Difference ◽  
Cord Injury ◽  
Operation Group

The objective of this study is to discuss the effect and mechanism of lithium chloride on the rehabilitation of locomotion post spinal cord injury (SCI) by observing the effect of lithium chloride on the expression of the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway. In total, 36 Sprague-Dawley (SD) rats were randomly divided into the sham operation group (n = 12), model group (n = 12), and lithium chloride group (n = 12). The sham operation group underwent laminectomy, while for the model group and the lithium chloride group with the NYU spinal cord impactor the SCI model was established. Basso, Beattie, and Bresnahan (BBB) score was used to evaluate locomotion after administration for 1, 3, 5, and 7 days, and the tissues were gathered for Nissl staining, transmission electron microscopy, immunofluorescence, and Western blot. With a statistical difference ( P < 0.05) on the 3rd day and significant difference ( P < 0.01) on the 5th day post administration, a higher BBB score was observed in the lithium chloride group indicating that lithium chloride improved the locomotion function after SCI. A better structure and morphology of neuron were observed by Nissl staining in the lithium chloride group. Lithium chloride promoted BDNF secretion from neurons in the spinal cord anterior horn with a significant difference compared to the model group ( P < 0.01). Compared with the model group, lithium chloride significantly promoted the expression of BDNF protein and phosphorylated TrkB protein ( P < 0.05), but no difference in the expression of TrkB was detected. Lithium chloride can alleviate the locomotion function after SCI with a mechanism that it can promote BDNF secretion from neurons in the spinal cord anterior horn and phosphorylation of TrkB to upregulate the BDNF/TrkB pathway supporting survival of neurons and regeneration and remyelination of axons.

scholarly journals Luhong Formula Has a Cardioprotective Effect on Left Ventricular Remodeling in Pressure-Overloaded Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Qian Liu ◽  
Hui-Yan Qu ◽  
Hua Zhou ◽  
Jing-Feng Rong ◽  
Tian-Shu Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Caspase 3 ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Sham Operation ◽  
Model Group ◽  
Enos Expression ◽  
Sham Operation Group ◽  
Operation Group

Background. Luhong formula (LHF)—a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Codonopsis pilosula (Franch.) Nannf., Cinnamomum cassia Presl, and Lepidium apetalum Willd—is used in the treatment of heart failure, but little is known about its mechanism of action. We have investigated the effects of LHF on antifibrosis. Methods. Forty-eight SD male rats were randomly assigned into six groups (n = 8), model group, sham-operation group, perindopril group (0.036 mg/ml), LHF high doses (LHF-H, 1.44 g/mL), LHF middle doses (LHF-M, 0.72 g/mL), and LHF low doses (LHF-L, 0.36 g/mL). Except the sham-operation group, the other groups were received an abdominal aorta constriction to establish a model of myocardial hypertrophy. The HW and LVW were measured to calculate the LVW/BW and HW/BW. ELISA was used to detect the serum concentration of BNP. The expressions of eNOS, TGF-β1, caspase-3, VEGF, and VEGFR2 in heart tissues were assessed by western blot analysis. mRNA expressions of eNOS, Col1a1, Col3a1, TGF-β1, VEGF, and VEGFR2 in heart tissues were measured by RT-PCR. The specimens were stained with hematoxylin-eosin (HE) and picrosirius red staining for observing the morphological characteristics and collagen fibers I and III of the myocardium under a light microscope. Results. LHF significantly lowered the rat’s HW/BW and LVM/BW, and the level of BNP in the LHF-treated group compared with the model group. Histopathological and pathomorphological changes of collagen fibers I and III showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF upregulated eNOS expression in heart tissue and downregulated Col1a1, Col3a1, TGF-β1, caspase-3, VEGF, and VEGFR2 expression. Conclusion. LHF can improve left ventricular remodeling in a pressure-overloaded heart failure rat model; this cardiac protective ability may be due to cardiac fibrosis and attenuated apoptosis. Upregulated eNOS expression and downregulated Col1a1, Col3a1, TGF-β1, caspase-3, VEGF, and VEGFR2 expression may play a role in the observed LHF cardioprotective effect.

Research on Action of Bone Marrow Stromal Cells (BMSC) Modified by Toll-Like Receptor for Myocardial Function of Rats with Myocardial Infarction (MI)

2021 ◽  
Vol 11 (9) ◽  
pp. 1832-1837
Author(s):  
Zhongkui Li ◽  
Wenbo Liu ◽  
Lufang Gao ◽  
Daokang Xiang
Keyword(s):  
Myocardial Function ◽  
Regulatory Action ◽  
Sham Operation ◽  
Toll Like Receptor ◽  
Model Group ◽  
Degree Of Deformation ◽  
Sham Operation Group ◽  
Sd Rats ◽  
Tlr4 Agonist ◽  
Operation Group

MI could affect myocardial function seriously. The action and mechanism of BSMC modified by the transplantation of Toll-like receptor on myocardial function of rats with MI was studied. The sixty SD rats were divided into sham-operation group and model group randomly. The isolated and cultivated BMSC was divided into three groups such as group with added by TLR4 agonist, group with added by TLR-4 antagonist as TAK-242, group with only BMSC. The model of rats with MT was established in model group. BMSC in different group was transplanted into rats respectively. The cardiac function of rats in sham-operation group and model group was observed. The distribution condition of surface molecule in BMSC was detected by FCM. There was expression CD44 (+), CD54 (+), CD90 (+), no expression CD34 (−) from results. It could indicated that BMSCs with high purity was cultivated successfully. The high MT expression was affected by TLR-4 generally which could also illustrate the degree of deformation and necrosis of cardiac muscle cell, could be enhanced in established rat model because of negative regulatory action. The zone of MI in rats could be amplified by TLR-4. The cytobiological function of BMSC could be adjusted by TLR-4 through the transplantation of TLR-4 after there was MI in rats. The cytobiological function of BMSC could be adjusted by TLR-4 through modification of the transplantation of TLT-4 in rats after there was MI in rats. The BMSCs modified by high TLR-4 expression had negative regulatory action on the treatment on MI.

scholarly journals The Protecting Effects and Mechanisms of Baicalin and Octreotide on Heart Injury in Rats with SAP

2007 ◽  
Vol 2007 ◽  
pp. 1-11 ◽  
Author(s):  
Zhang Xiping ◽  
Tian Hua ◽  
Chen Hanqing ◽  
Chen Li ◽  
Wang Zhiwei ◽  
...  
Keyword(s):  
Protein Expression ◽  
Caspase 3 ◽  
Treated Group ◽  
Myocardial Cell ◽  
Sham Operation ◽  
Model Group ◽  
Expression Levels ◽  
Sham Operation Group ◽  
Heart Injury ◽  
Operation Group

Purpose.To observe the protecting effects and mechanisms of Baicalin and Octreotide on heart injury in rats with severe acute pancreatitis (SAP).Methods.The SAP rat models were randomly divided into the model group, Baicalin-treated group, Octreotide treated group, and sham operation group. The contents of some inflammatory indexes in blood were determined. The rat mortality, pathological changes of heart, the changes ofNF-κB, P-Selectin, Bax, Bcl-2, and Caspase-3 protein expression levels as well as apoptotic index were observed in all groups, respectively, at 3 hours, 6 hours, and 12 hours after operation.Results.The survival rate of model group was less than treated groups at 12 hours, difference was significant. The contents of some inflammatory indexes of the treated groups were lower than those of the model group to various degrees at different time points. The pathological myocardial changes under light microscope were milder in treated groups than in model group. The changes ofNF-κB, P-Selectin, Bax, Bcl-2, and Caspase-3 protein expression levels in all groups were different. There was only a case of myocardial cell apoptosis in an Octreotide-treated group at 6 hours.Conclusion.Baicalin and Octreotide have protecting effects on heart injury of rats with SAP.

Yiqi Dingxuan Yin improves cerebral ischaemic injury in rats by inhibiting apoptosis and promoting angiogenesis

2021 ◽  
Author(s):  
Fei Liu ◽  
Liuyang Xie ◽  
Chunhua Liu ◽  
Guilian He ◽  
Chunyun Yuan ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cerebral Ischaemia ◽  
Neurological Function ◽  
Neural Function ◽  
Sham Operation ◽  
Nerve Function ◽  
Model Group ◽  
Expression Levels ◽  
Sham Operation Group ◽  
Operation Group

Abstract Background Clinically, Yiqi Dingxuan Yin promotes nerve function recovery and improves nerve function defect symptoms; however, the underlying molecular pathways remain unknown. In this study, we established a rat model of cerebral ischaemia induced by middle cerebral artery occlusion (MCAO). The effects of Yiqi Dingxuan Yin on the neurological function and local neuron morphology were compared with those of butylphthalide, which is used to treat ischemic stroke, and the possible mechanisms of action were explored. Methods Of 97 healthy adult male Sprague‒Dawley rats, 20 were randomly assigned to the sham operation group. The remaining rats underwent MCAO. Model generation was successful in 60 rats, which were randomly divided into a model group, butylphthalide group, and Yiqi Dingxuan Yin group (n = 20/group) administered distilled water, butylphthalide capsule, and Yiqi Dingxuan Yin, respectively. Zea-Longa scores were used to assess the neurological function of the rats at 1, 3, 7, and 14 days. Haematoxylin and eosin staining of brain sections was used to observe morphological changes in the rat hippocampus. Apoptosis of nerve cells was detected using TUNEL staining. The expression levels of erythropoietin/erythropoietin receptor (EPO/EPOR), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor/tyrosine receptor kinase B (BDNF/TrkB) protein in the ischaemic brain tissue were detected using immunohistochemistry. Results The apoptosis rate, and EPO/EPOR, VEGF, and BDNF/TrkB expression levels were higher in the model group than in the sham operation group (P < 0.05). Among MCAO groups, the nerve function deficit score and cell apoptosis rate were lower (P < 0.05), whereas the EPO/EPOR, VEGF, and BDNF/TrkB protein expression levels were higher (P < 0.05) in both the butylphthalide and Yiqi Dingxuan Yin groups than in the model group. Conclusions Yiqi Dingxuan Yin can improve the neural function and morphology of neurons after cerebral ischaemia injury in rats, with a more significant effect at 14 days. This may be related to the upregulation of EPO/EPOR, VEGF, and BDNF/TrkB protein expression, which may promote angiogenesis to improve cerebral blood flow and oxygen supply, thereby protecting the form and function of neurons and promoting the restoration of impaired neural function.

Rosuvastatin Calcium Affects Alzheimer's Disease Through Regulating Defensive Transduction Pathways of Oxidative and Chemical Stress Signaling Pathway

2019 ◽  
Vol 9 (10) ◽  
pp. 1414-1419
Author(s):  
Zhongjin Liu ◽  
Ruiqing Li ◽  
Chunmei Zhang ◽  
Jia Liu ◽  
Haiyan Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Ability ◽  
Signaling Pathway ◽  
Neuronal Damage ◽  
Sham Operation ◽  
Sod Activity ◽  
Sham Operation Group ◽  
Operation Group ◽  
Rosuvastatin Calcium

Alzheimer's disease (AD) treatment is not effective. Statins are lipid-lowering drugs. However, the role and mechanism of statins for treating AD remains unclear. SD rats were separated into sham operation group; AD group and rosuvastatin calcium group followed by analysis of cognitive function and neuronal morphology. ELISA was to measure the level of TNF-α and IL-1; SOD activity and ROS levels were measured,. Real-time quantitative PCR was to analyze Bcl-2 and Bax level. The expression of Nuclear Erythroid 2-Related Factor 2/Antioxidant Responsive Element (NRF2/ARE) signaling pathway was analyzed by Western blot. Compared with sham operation group, the cognitive ability of the AD group was significantly decreased; with elevated secretion of TNF-α and IL-1, decreased SOD activity, increased ROS generation, decreased Bcl-2 expression as well as increased Bax expression (P < 0.05). In addition, AD group rats showed neuronal damage in the hippocampus and decreased expression of NRF2 and ARE. However, rosuvastatin calcium treatment improved cognitive ability, decreased TNF-α and IL-1 secretion, increased SOD activity, decreased ROS content, increased Bcl-2 expression and decreased Bax expression as well as ameliorated neuronal damage, increased number of nerve cells, and increased expression of NRF2 and ARE. Rosuvastatin calcium can inhibit the oxidative stress and inflammation, inhibit the apoptosis of hippocampus cells and improve the cognitive ability of AD rats by regulating NRF2/ARE signaling pathway.

scholarly journals Da-Huang-Fu-Zi-Tang Ameliorates Severe Acute Pancreatitis by Elevation of M2 Kupffer Cells in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yi Song ◽  
Yi Wang ◽  
Xin Qi ◽  
Xin Kang ◽  
Xiaoguang Lu
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Kupffer Cells ◽  
Sham Operation ◽  
Inflammatory Factor ◽  
Model Group ◽  
Sham Operation Group ◽  
Tnf Α ◽  
Operation Group ◽  
High Level

Introduction. Severe acute pancreatitis (SAP) is a clinical emergency often accompanied by inflammatory response syndrome (SIRS), which eventually leads to acute lung injury and failure of other organs. The activation of liver Kupffer cells (KCs) plays a major role in the process of SIRS and multiorgan damage caused by SAP. Da-Huang-Fu-Zi-Tang (DHFZT), a traditional Chinese prescription, has been widely used for SAP in the clinic. The present study investigated the activation state of KCs in SAP and the potential mechanism of DHFZT. Methods. A total of 24 Sprague Dawley rats were randomly assigned to four groups: SH (sham operation group + saline enema), SH-DHFZT (sham operation group + DHFZT enema), SAP (model group + saline enema), and SAP-DHFZT (model group + DHFZT enema). Blood samples were drawn from the abdominal aorta for measuring serum endotoxin, amylase, calcium ion, IL-1β, TNF-α, iNOS, and IL-10. Then, the pancreas, lung, liver, and ileum were harvested for histological observation, and the liver was used to detect the level of F4/80, CD86, and CD163 in KCs with immunohistochemistry and western blot. Results. In the SAP group, the CD86+ KCs were significantly increased with a high level of IL-1β, TNF-α, and iNOS, and the organs were impaired. In the SAP-DHFZT group, CD163+ KCs were significantly increased with the high level of IL-10, and the damage to organs was alleviated. Conclusion. These phenomena suggested that the SIRS and multiple organ damage in SAP might be related to the excessive activation of M1 KCs, and DHFZT might alleviate the SIRS by inducing the differentiation of KCs into the M2-type and promote the expression of anti-inflammatory factor IL-10.

scholarly journals Oleanolic Acid Ameliorates Aβ25-35 Injection-induced Memory Deficit in Alzheimer’s Disease Model Rats by Maintaining Synaptic Plasticity

2018 ◽  
Vol 17 (5) ◽  
pp. 389-399 ◽  
Author(s):  
Kai Wang ◽  
Weiming Sun ◽  
Linlin Zhang ◽  
Wei Guo ◽  
Jiachun Xu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Oleanolic Acid ◽  
Memory Deficit ◽  
Sham Operation ◽  
Group Model ◽  
Model Group ◽  
Sham Operation Group ◽  
Operation Group

Background: Abnormal amyloid β (Aβ) accumulation and deposition in the hippocampus is an essential process in Alzheimer’s disease (AD). Objective: To investigate whether Oleanolic acid (OA) could improve memory deficit in AD model and its possible mechanism. Methods: Forty-five SD rats were randomly divided into sham operation group, model group, and OA group. AD models by injection of Aβ25-35 were built. Morris water maze (MWM) was applied to investigate learning and memory, transmission electron microscope (TEM) to observe the ultrastructure of synapse, western blot to the proteins, electrophysiology for long-term potentiation (LTP), and Ca2+ concentration in synapse was also measured. Results: The latency time in model group was significantly longer than that in sham operation group (P=0.0001); while it was significantly shorter in the OA group than that in model group (P=0.0001); compared with model group, the times of cross-platform in OA group significantly increased (P=0.0001). TEM results showed OA could alleviate neuron damage and synapses changes induced by Aβ25-35. The expressions of CaMKII, PKC, NMDAR2B, BDNF, TrkB, and CREB protein were significantly improved by OA (P=0.0001, 0.036, 0.041, 0.0001, 0.0001, 0.026, respectively) compared with that in model group; the concentration of Ca2+ was significantly lower in OA group (1.11±0.42) than that in model group (1.68±0.18); and the slope rate (P=0.0001) and amplitude (P=0.0001) of f- EPSP significantly increased in OA group. Conclusion: The present results support that OA could ameliorate Aβ-induced memory loss of AD rats by maintaining synaptic plasticity of the hippocampus.

scholarly journals Protecting Effects of Dexamethasone on Thymus of Rats with Severe Acute Pancreatitis

2007 ◽  
Vol 2007 ◽  
pp. 1-9 ◽  
Author(s):  
Zhang Xiping ◽  
Chen Li ◽  
Lin Miao ◽  
Tian Hua
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Caspase 3 ◽  
Treated Group ◽  
Apoptotic Index ◽  
Sham Operation ◽  
Model Group ◽  
Sham Operation Group ◽  
Time Points ◽  
Operation Group

Purpose. To study the protecting effects of dexamethasone on thymus of rats with severe acute pancreatitis (SAP).Methods. The SAP rats were randomly assigned to the model group and dexamethasone-treated group, the other normal healthy rats were assigned to the sham operation group. The rat survival, thymus pathological changes, apoptotic index, as well as expression levels of NF-κB, P-selectin, Bax, Bcl-2, and Caspase-3 protein of all groups were observed, respectively, at 3 hours, 6 hours, and 12 hours. The contents of amylase and endotoxin in plasma as well as the contents of TNF-α,PLA2, and NO in serum were determined.Results. There was no marked difference between the model group and treated group in survival. The contents of different indexes in blood of treated group were lower than those of the model group to various degrees at different time points. The thymus pathological score was lower in treated group than in model group at 12 hours.The treated group in Caspase-3 protein expression of thymus significantly exceeded the model group at 12 hours. The apoptotic index was significantly higher in treated group than in model group.Conclusion. Dexamethasone has protecting effects on thymus of SAP rats.

scholarly journals Role of Acupoint Area Collagen Fibers in Anti-Inflammation of Acupuncture Lifting and Thrusting Manipulation

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Fan Wang ◽  
Guang-wei Cui ◽  
Le Kuai ◽  
Jian-min Xu ◽  
Ting-ting Zhang ◽  
...  
Keyword(s):  
Collagen Fiber ◽  
Collagen Fibers ◽  
Sham Operation ◽  
Model Group ◽  
Fiber Morphology ◽  
Sham Operation Group ◽  
Group A ◽  
Operation Group ◽  
Anti Inflammation

The role of the acupoint area collagen fibers in the efficacy of acupuncture lifting and thrusting (L&T) manipulation will be explored in this paper. 30 male NZW rabbits were randomly divided into 6 groups: sham operation group (Group N), model group (Group M), acupuncture without manipulation group (Group W), acupuncture L&T manipulation group (Group A), collagenase pretreatment group (Group JM), and collagenase pretreatment + acupuncture L&T manipulation group (Group JA). The bacterial endotoxin was used to generate the rabbit fever models. Acupuncture was applied at IL-11. The levels of IL-1β, TNF-α, and IL-4 and the rectal temperature were measured at 2 h, 4 h, and 6 h after modeling and the collagen fiber morphology at acupoint area was observed after 6 hours.Results.As compared with Group N, the levels of IL-1βand TNF-αin Group M were significantly higher; the level of IL-4 was significantly lower (P<0.05). As compared with Group M, IL-1βand TNF-αin Groups W and A were significantly lower and IL-4 was significantly higher (P<0.05). As compared with Group W, IL-1βand TNF-αin Group A were lower and IL-4 was higher (P<0.05). The collagen fiber in Group A was slightly rough, distorted, and fractured. As shown in studies, the endotoxin-induced inflammatory response can be significantly inhibited by acupuncture whose efficacy can also be significantly improved by the manipulations. Collagenase pretreatment may be the first receptor to the mechanical force of the L&T manipulation.

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