关键词：
miR-34a;Survivin;Platycodin D;Susceptibility;Gastric cancer
摘要：
INTRODUCTION: Platycodin D (PD), a triterpenoid saponin isolated from Platycodon grandiflorum, has a well-known anti-tumor effect in multiple human cancers, including gastric cancer (GC). miR-34a plays an important role in the progression of GC. However, the relationship between miR-34a and the susceptibility of GC cells to PD is still unclear. The aim of our research was to investigate the functions of miR-34a in mediating the susceptibility of GC to PD. METHODS: qPCR was performed to detect the expression level of miR-34a and survivin in GC cells. The expression of survivin, Bcl-2, Bax, and cleaved caspase-3 was analyzed using Western blot. Cell viability was detected by MTT assay, and apoptosis was analyzed via Annexin V-FITC/PI staining followed by flow cy-tometry. The colony formation and scratch-wound assays were applied to assess cell proliferation and migration. Caspase-3/7 activity was detected by a Caspase-Glo(R)3/7 detection kit. The relationship between miR-34a and survivin was determined by dual luciferase reporter gene assay. Finally, a GC xenograft mouse model was used to confirm our findings in vivo. RESULTS: The expression of miR-34a decreased but survivin increased inversely in human GC cells. Survivin is a direct target of miR-34a and may be negatively regulated by miR-34a. PD could inhibit GC cell proliferation and induce apoptosis. Importantly, overexpression miR-34a or suppressing survivin was shown to enhance the susceptibility of GC to PD both in vitro and in vivo. CONCLUSIONS: miR-34a could modulate the susceptibility of GC to PD via targeting survivin, suggesting miR-34a overexpression may serve as a novel strategy to sensitize GC to anti-cancer drugs.
期刊：
Prostaglandins & Other Lipid Mediators,2019年140:1-8 ISSN：1098-8823
通讯作者：
Zou, Guohui;Deng, Changqing
作者机构：
[Chen, Hongtao; Zou, Guohui; Liu, Zhongyong; Xu, Ri; Deng, Peng] Jiangxi Univ Tradit Chinese Med, Affiliated Hosp, Nanchang 330006, Jiangxi, Peoples R China.;[Zhu, Jinhua] Jiangxi Univ Tradit Chinese Med, Nanchang 330004, Jiangxi, Peoples R China.;[Wu, Lu] Hunan Univ Tradit Chinese Med, Affiliated Tradit & Western Med Hosp 2, Liuyang 410300, Peoples R China.;[Deng, Changqing] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Zou, Guohui] J;[Deng, Changqing] H;Jiangxi Univ Tradit Chinese Med, Affiliated Hosp, Nanchang 330006, Jiangxi, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.
关键词：
*Detoxification and activating blood circulation decoction;*Inflammatory reaction;*PCI operation;*Restenosis;*TLR4/NF-kappaB;*VSMCs proliferation
摘要：
Restenosis is a major problem after percutaneous coronary intervention (PCI) treatment. Inflammation is one of the major core mechanisms involved in the occurrence of restenosis, and plays an important role in intimal hyperplasia. Detoxification and activating blood circulation decoction (DABCD) is a traditional Chinese medicine that is used in the treatment and prevention of atherosclerotic and inflammatory diseases. Our previous studies demonstrated that DABCD-mediated cardioprotection involves anti-inflammatory mechanisms and could be developed as a novel drug for the treatment of vascular smooth muscle cell (VSMC) proliferation and aortic restenosis. A rat model of postoperative restenosis after PCI was generated by balloon injury to determine the protective effects and potential mechanisms of DABCD. The injured segments of aortae were collected on days 14 and 28 after the operation to observe the morphological changes in the vascular structure and measure the proportion of inflammatory factors in plasma and vascular tissues, as well as test the proliferative activity of VSMCs. The expression of related proteins, namely, Toll-like receptor (TLR) 4 and nuclear factor (NF)-kappaB, in the mechanistic study was clarified by western blot analysis. We tested the hypothesis that the cardioprotective effects of DABCD on aortic restenosis are associated with the inhibition of aortic intimal hyperplasia in this model. Our results showed that DABCD has protective effect on rat aortic restenosis and the anti-inflammatory mechanism of DABCD on balloon-induced restenosis in rat may be due to its ability to inhibit TLR4-mediated NF-kappaB signaling pathways. DABCD may be a potential therapeutic agent against restenosis.
摘要：
Collagen triple helix repeat containing 1 (CTHRC1) is a gene that has been associated with tumor progression in human prostate cancer (PC). The tumor immune microenvironment has been linked with disease outcome in PC. In the present study, the correlation between CTHRC1 with PC recurrence and the tumor immunological microenvironment was investigated. Using the data supplied by the Tumor Immune Estimation Resource (TIMER), the expression of CTHRC1, programmed cell death protein 1 (PD-1), and programmed cell death 1 ligand 1 (PD-L1) were analyzed. Immunohistochemical staining of CTHRC1, PD-1 and PD-L1 was performed using a tissue microarray construction of prostate adenocarcinoma (PRAD) specimens. In PRAD, an association was reported between the CTHRC1 expression and the disease free survival (DFS) rate (P=0.022). Overexpression of CTHRC1 was correlated with increased levels of PD-1 (R=0.272, P=0.021) and PD-L1 (R=0.298, P=0.016), elevated levels of infiltrating B cells (P=9.51e(-11)), CD4(+) cells (P=1.51e(-11)), macrophages (P=8.25e(-5)), neutrophils (P=2.17e(-9)) and dendritic cells (P=3.13e(-13)). Bioinformatics analysis revealed that CTHRC1 was correlated with the expression levels of matrix metalloproteinase-9, mucin 1 and solute carrier organic anion transporter family member 2B1 genes, which exert an influence in PRAD. The occurrence of this condition is most likely to be associated with regulation of the tumor microenvironment. Taken together, we demonstrated that the prognosis and immunity of PC are closely linked to CTHRC1 upregulation. Furthermore, these results suggest that the immune function of PC may be suppressed by CTHRC1-targeting therapy.
期刊：
Medical Science Monitor,2019年25:5389-5400 ISSN：1643-3750
通讯作者：
Luo, Yinhe;Wang, Mengqing
作者机构：
[Zhang, Xin; Chen, Xingyu; Ding, Yi; Yang, Jingyi; Sun, Le; Li, Yan; Huang, Kailing; Chen, Yingying; Jiao, Luojia; Huang, Ting] Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.;[Luo, Yinhe] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Wang, Mengqing] Hunan Univ Chinese Med, Domest Class Discipline Construc Project Chinese, Changsha, Hunan, Peoples R China.
通讯机构：
[Luo, Yinhe; Wang, Mengqing] H;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Domest Class Discipline Construc Project Chinese, Changsha, Hunan, Peoples R China.
摘要：
Background: Dendritic cell autophagy plays a pivotal role in asthma. Wuhu decoction can significantly improve respiratory syncytial virus (RSV) bronchiolitis and delay its development into asthma. The aim of the present study was to explore the therapeutic effect and mechanism of Wuhu decoction on RSV -induced asthma in mice. Material/Methods: Establishment of asthmatic mice model was induced by RSV. Hematoxylin-eosin staining, periodic acid-Schiff (PAS) staining, and Masson trichrome staining were performed to observe pathological changes in the lungs. The levels of CD4(+) T, CD8(+) T, and CD4(+) CD25(+) T in blood were analyzed by flow cytometry. The contents of interleukin (IL)-4, interferon-gamma (IFN-gamma), IL-10, and IL-13 in serum were measured by enzyme-linked immunosorbent assay (ELISA). The number of autophagosomes in dendritic cells (DCs) of lung tissue was observed by transmission electron microscope. The DCs of lung tissue were isolated by magnetic bead sorting. The levels of LC3-II, Beclin-1, and LC3-I in DCs and MMP-9, TIMP-1, AMPK, p-AMPK, ULK1, and LK1 expression in lung tissues were detected by western blot. Real-time polymerase chain reaction (PCR) detected the expression of AMPK and ULK1 genes. Results: Wuhu decoction can effectively alleviate chronic airway inflammation and airway remodeling and reduce airway hyperresponsiveness. Moreover, Wuhu decoction can significantly enhance the level of autophagy in DCs of lung tissue and promote the expression of AMPK and ULK1 in lung tissue. Conclusions: Wuhu decoction may improve the RSV-induced asthmatic symptoms by enhancing autophagy of DCs in lung tissue dependent on the AMPK/ULK1 signaling pathway.
摘要：
Purpose: There is no effective treatment for liver fibrosis, which is a common phase during the progression of many chronic liver diseases to cirrhosis. Previous studies found that Semen Brassicae therapy can effectively improve the clinical symptoms of patients with asthma, allergic rhinitis, and chronic lung diseases; however, its effects on liver fibrosis in rats and its possible mechanisms of action remain unclear. Methods: Rats were injected intraperitoneally with 4% thioacetamide aqueous solution (5 mL.kg(-1)) at a dose of 200 mg.kg(-1) twice a week for 8 consecutive weeks to establish the liver fibrosis model and were then treated with different concentrations of Semen Brassicae extract. A tier Semen Brassicae treatment, the morphology of the liver tissue was analyzed using hematoxylin and eosin and Masson's trichrome staining, and liver index and liver fibrosis grade were calculated. Thereafter, the levels of collagen-I, collagen-III, alpha-SM A, transforming growth factor (TGF)-beta 1, p-Smad 2/3, Smad 2/3, Smad4, NF-kappa B-p65, p-NF-kappa B-p65, IL-1 beta, IL-6, AKT, and p-AKT were determined using Western blotting. Results: Compared with the untreated model group, the Semen Brassicae-treated group showed significantly decreased liver function indices; expression levels of collagen-I, collagen-III, and alpha-SMA; and hepatic fibrosis. Further studies also showed that the expression of TGF-beta 1, Smad4, p-Smad 2/3, Smad 2/3,, p-NF-kappa B-p65/NF-KB-p65, IL-1 beta, IL-6, and p-AKT/AKT significantly decreased after the treatment. Conclusion: These results indicate that Semen Brassicae exhibits an anti-hepatic fibrosis effect, and the underlying mechanism of action may be related to the regulation of TGF-beta 1/Smad, NF-kappa B, and AKT signaling pathways and the reduction of extracellular matrix deposition.
期刊：
Evidence-Based Complementary and Alternative Medicine,2018年2018:5290514 ISSN：1741-427X
通讯作者：
Yan, Miao;Fan, Xin-Rong
作者机构：
[Yan, Miao; Zhang, Ling] Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China.;[Zhang, Ling; Fan, Xin-Rong] China Acad Chinese Med Sci, Inst BasicTheory Chinese Med, Beijing 100700, Peoples R China.;[He, Qing-Hu; Nie, Yu-Song; Zhang, Ling; Fan, Xin-Rong; Xie, Hui] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Zhang, Min] Shanxi Univ Chinese Med, Clin Med Coll 1, Xianyang 712000, Shanxi, Peoples R China.
通讯机构：
[Yan, Miao; Fan, Xin-Rong] C;[Fan, Xin-Rong] H;Cent South Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China.;China Acad Chinese Med Sci, Inst BasicTheory Chinese Med, Beijing 100700, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.
摘要：
Isoprenoids and prenylated proteins regulate a variety of cellular functions, including neurite growth and synaptic plasticity. Importantly, they are implicated in the pathogenesis of several diseases, including Alzheimer's disease (AD). Recently, we have shown that two protein prenyltransferases, farnesyltransferase (FT) and geranylgeranyltransferase-1 (GGT), have differential effects in a mouse model of AD. Haplodeficiency of either FT or GGT attenuates amyloid-beta deposition and neuroinflammation but only reduction in FT rescues cognitive function. The current study aimed to elucidate the potential mechanisms that may account for the lack of cognitive benefit in GGT-haplodeficient mice, despite attenuated neuropathology. The results showed that the magnitude of long-term potentiation (LTP) was markedly suppressed in hippocampal slices from GGT-haplodeficient mice. Consistent with the synaptic dysfunction, there was a significant decrease in cortical spine density and cognitive function in GGT-haplodeficient mice. To further study the neuron-specific effects of GGT deficiency, we generated conditional forebrain neuron-specific GGT-knockout (GGT(f/f)Cre+) mice using a Cre/LoxP system under the CAMKII alpha promoter. We found that both the magnitude of hippocampal LTP and the dendritic spine density of cortical neurons were decreased in GGT(f/f)Cre+ mice compared with GGT(f/f)Cre- mice. Immunoblot analyses of cerebral lysate showed a significant reduction in cell membrane-associated (geranylgeranylated) Rac1 and RhoA but not (farnesylated) H-Ras, in GGT(f/f)Cre+ mice, suggesting that insufficient geranylgeranylation of the Rho family of small GTPases may underlie the detrimental effects of GGT deficiency. These findings reinforce the critical role of GGT in maintaining spine structure and synaptic/cognitive function in development and in the mature brain. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
作者机构：
[Peng, Tingting; Tang, Qianli; Liao, Xianjiu] Youjiang Med Univ Nationalities, West Guangxi Key Lab Prevent & Treatment High Inc, 98 Chengxiang Rd, Baise 533000, Guangxi, Peoples R China.;[Li, Liqing; Ge, Bin; Tang, Qianli; Liao, Xianjiu] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Pan, Jianbin] Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Analyt Chem Life Sci, Nanjing, Jiangsu, Peoples R China.
通讯机构：
[Tang, Qianli] Y;Youjiang Med Univ Nationalities, West Guangxi Key Lab Prevent & Treatment High Inc, 98 Chengxiang Rd, Baise 533000, Guangxi, Peoples R China.
关键词：
carbon nitride nanosheet;catalytic hairpin assembly;intracellular signal amplification;microRNA;nanoprobe
摘要：
In this study, an ultrasensitive fluorescence turn-on assay for in situ sensing of intracellular microRNA (miRNA) was developed utilizing a carbon nitride nanosheet (CNNS) and a catalytic hairpin assembly (CHA). The CHA showed favourable signal amplification for low-level biomarkers, and CNNS was an excellent candidate as a fluorescence quencher and gene vector. Moreover, the hairpin DNA of CHA could be adsorbed onto the surface of CNNS. An enzyme-free fluorescence biosensor for ultrasensitive sensing of intracellular miRNA in cells based on CHA and CNNS was designed. When faced with target miRNA, the fluorescence was recovered due to the miRNA, which could trigger cycling of CHA circuits, leading to the production of a marked enhanced fluorescence signal. Compared with traditional methods, the proposed method is convenient, with low cytotoxicity, and high specificity and ultrasensitivity. It has promising potential for detection low-level biomarkers.
摘要：
Aims: The expression of phosphoglycerate kinase 1 (MMP19) is elevated in some cancers. However, the clinical features and prognostic value of glioma patients with MMP19 expression are unclear. In this study, the expression level of MMP19 and the correlation between the level of MMP19 expression and the clinicopathologic data in glioma patients including survival were examined. Methods and results: Using real-time PCR, the mRNA expression of MMP19 was examined in 61 fresh glioma tissues and 32 brain samples. The result indicated that MMP19 mRNA was obviously elevated in glioma tissues compared to brain tissues. Further, we observed that MMP19 mRNA was much higher in stage III patients than it was in stage I-II patients. The expression of the MMP19 protein was determined by immunohistochemical analysis in 156 paraffin-embedded glioma samples and 35 normal paraffin-embedded brain samples. The MMP19 protein level was significantly increased in glioma tissues compared to brain tissues (P = 0.008). Furthermore, we observed that a high expression of MMP19 protein was positively associated with clinical stage (P = 0.008) but did not correlate with age, gender, or histological type. An increased MMP19 protein expression was associated with poor overall survival rates (P = 0.001). A stratified analysis showed that patients with high MMP19 protein expression indicated a worse prognosis occurring in WHO III-IV stages (P = 0.001). A Multivariate analysis indicated that a high expression of the MMP19 protein was an independent prognostic indicator of patient survival (P = 0.009). Conclusions: MMP19 is overexpressed and plays a significant role in disease progression and poor outcome in glioma patients.
关键词：
total Astragalus extract;total Panax notoginseng saponins;combination;cerebral ischemiareperfusion;energy metabolism;C-Jun N-terminal kinase signal transduction;mitochondrial apoptosis pathway;Chinese medicine
摘要：
Objective: To explore the effects and molecular mechanisms of the combination between total Astragalus extract (TAE) and total Panax notoginseng saponins (TPNS) against cerebral ischemiareperfusion injury. Methods: C57BL/6 mice were randomly divided into sham-operated group, model group, TAE (110 mg/kg) group, TPNS (115 mg/kg) group, TAE-TPNS combination group and Edaravone (4 mg/kg) group, treated for 4 days, then, cerebral ischemia-reperfusion injury was established by bilateral common carotid artery (CCA) ligation for 20 min followed by reperfusion for 1 and 24 h. Results: TPNS could increase adenosine triphosphate (ATP) level, TAE and TAE-TPNS combination increased ATP, adenosine diphosphate (ADP) contents and Na~+-K~+-ATPase activity, and the effects of TAE-TPNS combination were stronger than those of TAE or TPNS alone after reperfusion for 1 h. After reperfusion for 24 h, TAE, TPNS and TAE-TPNS combination significantly increased neurocyte survival rate and decreased the apoptosis rate as well as down-regulated the expression of phosphorylated c-June N-terminal kinase1/2 (p-JNK1/2), cytochrome C (Cyt C), cysteine aspartic acid-specific protease (Caspase)-9 and Caspase-3. Furthermore, the effects in TAE-TPNS combination were better than those in TAE or TPNS alone. Conclusion: The combination of TAE 110 mg/kg and TPNS 115 mg/kg could strengthen protective effects on cerebral ischemia injury, the mechanism underlying might be related to improving jointly the early energy metabolism, and relieving the delayed apoptosis via inhibiting the mitochondrial apoptosis pathway of JNK signal transduction.
摘要：
Danggui Buxue Tang (DBT), a combination of Astragalus and Angelica at a 5 : 1 ratio, mainly promotes hematopoiesis. However, in the clinic, the combination ratio of Astragalus and Angelica to treat low hematopoietic function is not an absolute 5 : 1 ratio, suggesting that the herbs may promote hematopoiesis better after being combined at a certain range of ratios. The objective of this study is to investigate the effect of different ratio combinations of Astragalus and Angelica on bone marrow hematopoiesis suppression induced by cyclophosphamide (CTX) and to probe the interaction and mechanism of Astragalus combined with Angelica in promoting hematopoiesis. Following establishment of the model, mice were administered with Astragalus (6.00 g.kg(-1)), Angelica (3.00 g.kg(-1)), and combinations of Astragalus and Angelica at different ratios, including 10 : 1 (Astragalus 9.81 g.kg(-1)+Angelica 0.98 g.kg(-1)), 5 : 1 (Astragalus 9.00 g.kg(-1)+Angelica 1.80 g.kg(-1)), 2 : 1 (Astragalus 7.71 g.kg(-1)+Angelica 3.08 g.kg(-1)), 1 : 1 (Astragalus 5.40 g.kg(-1)+Angelica 5.40 g.kg(-1)), 1 : 2.5 (Astragalus 3.08 g.kg(-1)+Angelica 7.71 g.kg(-1)), 1 : 5 (Astragalus 1.80 g.kg(-1)+Angelica 9.00 g.kg(-1)), and 1 : 10 (Astragalus 0.98 g.kg(-1)+Angelica 9.81 g.kg(-1)). Our results suggested that Astragalus mixed with Angelica synergistically promoted hematopoiesis best when the combination ratio of Astragalus and Angelica was 1 : 1, 1 : 2.5 or 1 : 5; moreover, the effect of Angelica was greater than that of Astragalus. The potential mechanisms of the combinations of Astragalus and Angelica that promote hematopoiesis include the dissolution of the effective components, promoting the synthesis and secretion of hematopoietic growth factor (HGF) and the proliferation of hematopoietic progenitor cells (HPCs).
摘要：
The aim of this study was to explore the effect by which the combination of Astragaloside IV (AST IV) and Ginsenoside Rg1 (Rg1) resisted autophagic injury in PC12 cells induced by oxygen glucose deprivation/reoxygenation (OGD/R). We studied the nature of the interaction between AST IV and Rg1 that inhibited autophagy through the Isobologram method, and investigated the synergistic mechanism via the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways. Our results showed that, based on the 50% inhibiting concentration (IC50), AST IV combined with Rg1 at a 1:1 ratio resulted in a synergistic effect, whereas the combination of the two had an antagonistic effect on autophagy at ratios of 1:2 and 2:1. Meanwhile, AST IV and Rg1 alone increased cell survival and decreased lactate dehydrogenase (LDH) leakage induced by OGD/R, reduced autophagosomes and the LC3 II positive patch, down-regulated the LC3 II/LC3 I ratio and up-regulated the p62 protein; the 1:1 combination enhanced these effects. Mechanistic study showed that Rg1 and the 1:1 combination increased the phosphorylation of PI3K I, Akt and mTOR; the effects of the combination were greater than those of the drugs alone. AST IV and the 1:1 combination suppressed the expression of PI3K III and Becline-1, and the combination elevated Bcl-2 protein expression; the effects of the combination were better than those of the drugs alone. These results suggest that after 2 h-OGD followed by reoxygenation for 24 h, PC12 cells suffer excessive autophagy and damage, which are blocked by AST IV or Rg1; moreover, the combination of AST IV and Rg1 at a 1:1 ratio of their IC50 concentrations has a synergistic inhibition on autophagic injury. The synergistic mechanism may be associated with the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways. (C) 2017 Elsevier Masson SAS. All rights reserved.
摘要：
Danggui Buxue Tang (DBT), a combination of Astragalus and Angelica at a 5 : 1 ratio, mainly promotes hematopoiesis. However, in the clinic, the combination ratio of Astragalus and Angelica to treat low hematopoietic function is not an absolute 5 : 1 ratio, suggesting that the herbs may promote hematopoiesis better after being combined at a certain range of ratios. The objective of this study is to investigate the effect of different ratio combinations of Astragalus and Angelica on bone marrow hematopoiesis suppression induced by cyclophosphamide (CTX) and to probe the interaction and mechanism of Astragalus combined with Angelica in promoting hematopoiesis. Following establishment of the model, mice were administered with Astragalus (6.00 g.kg(-1)), Angelica (3.00 g.kg(-1)), and combinations of Astragalus and Angelica at different ratios, including 10 : 1 (Astragalus 9.81 g.kg(1)+Angelica 0.98 g.kg(-1)), 5 : 1 (Astragalus 9.00 g.kg(-1)+Angelica 1.80 g.kg(-1)), 2 : 1 (Astragalus 7.71 g.kg(-1)+Angelica 3.08 g.kg(-1)), 1 : 1 (Astragalus 5.40 g.kg(-1)+Angelica 5.40 g.kg(-1)), 1 : 2.5 (Astragalus 3.08 g.kg(-1)+Angelica 7.71 g.kg(-1)), 1 : 5 (Astragalus 1.80 g.kg(-1)+Angelica 9.00 g.kg(-1)), and 1 : 10 (Astragalus 0.98 g.kg(-1)+Angelica 9.81 g.kg(-1)). Our results suggested that Astragalus mixed with Angelica synergistically promoted hematopoiesis best when the combination ratio of Astragalus and Angelica was 1 : 1, 1 : 2.5 or 1 : 5; moreover, the effect of Angelica was greater than that of Astragalus. The potential mechanisms of the combinations of Astragalus and Angelica that promote hematopoiesis include the dissolution of the effective components, promoting the synthesis and secretion of hematopoietic growth factor (HGF) and the proliferation of hematopoietic progenitor cells (HPCs).
作者机构：
[Zeng, Heng; Chen, Jian-xiong; He, Xiaochen] Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, Sch Med, Jackson, MS 39216 USA.;[Liao, Duan-fang; Tuo, Qin-hui] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Zhang, Guo-qiang] China Japan Friendship Hosp, Emergency Dept, Beijing 100029, Peoples R China.
通讯机构：
[Chen, Jian-xiong] U;Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, Sch Med, Jackson, MS 39216 USA.
摘要：
Recent studies reveal a crucial role of pericyte loss in sepsis-associated microvascular dysfunction. Sirtuin 3 (SIRT3) mediates histone protein post-translational modification related to aging and ischemic disease. This study investigated the involvement of SIRT3 in LPS-induced pericyte loss and microvascular dysfunction. Mice were exposed to LPS, expression of Sirt3, HIF-2α, Notch3 and angiopoietins/Tie-2, pericyte/endothelial (EC) coverage and vascular permeability were assessed. Mice treated with LPS significantly reduced the expression of SIRT3, HIF-2α and Notch3 in the lung. Furthermore, exposure to LPS increased Ang-2 while inhibited Ang-1/Tie-2 expression with a reduced pericyte/EC coverage. Intriguingly, knockout of Sirt3 upregulated Ang-2, but downregulated Tie-2 and HIF-2α/Notch3 expression which resulted in a dramatic reduction of pericyte/EC coverage and exacerbation of LPS-induced vascular leakage. Conversely, overexpression of Sirt3 reduced Ang-2 expression and increased Ang-1/Tie-2 and HIF-2α/Notch3 expression in the LPS treated mice. Overexpression of Sirt3 further prevented LPS-induced pericyte loss and vascular leakage. This was accompanied by a significant reduction of the mortality rate. Specific knockout of prolyl hydroxylase-2 (PHD2) increased HIF-2α/Notch3 expression, improved pericyte/EC coverage and reduced the mortality rate in the LPS-treated mice. Our study demonstrates the importance of SIRT3 in preserving vascular integrity by targeting pericytes in the setting of LPS-induced sepsis.
摘要：
Ethnopharmacological relevance: Liuwei Dihaung decoction (LWDHT) is a well-known classic traditional Chinese medicine formula, consists of six herbs including Rehmannia glutinosa Libosch.(family: Scrophulariaceae), Cornus officinalis Sieb.(family: Cornaceae), Dioscorea opposite Thunb.(family: Dioscoreaceae), Alisma orientale(G. Samuelsson) Juz (family: Alismataceae), Poria cocos (Schw.) Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has been used in the treatment of many types of diseases with signs of deficiency of Yin in the kidneys in China clinically. This study is aimed at investigating the effect of Liuwei dihuang decoction on PI3K/Akt signaling pathway in liver of T2DM rats with insulin resistance. Materials and methods: T2DM model was induced in male Sprague-Dawley (SD) rats by high sugar and high fat diets combined with small dose of streptozocin (STZ) injection. The successful T2DM rats were randomly allocated three group-vehicle group, positive control group and Liuwei Dihuang decoction group. After 12-weeks treatment with distilled water, rosiglitazone and LWDHT by intragastric administration respectively, the rats were put to death in batches. The variance of fasting blood glucose (FBG) and fasting insulin (FINS) in serum were determined, the pathological changes of each rats' liver were observed by hematoxylin-eosin (HE) staining, the expression of insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinas B (Akt) involving the canonical PI3K/Akt signaling pathway were detected by Real-time fluorescent quantitative PCR (RT-PCR), and the expression level of IRS2, PI3K, Akt protein and phosphorylated IRS2, PI3K, Akt protein were evaluated by Western Blot. All the data were analyzed by SPSS 17.0. Results: Four weeks of treatment with LWDHT could significantly decrease the level of FBG and FINS in serum, improve the cellular morphology of liver, kidney, pancreas tissue, and the expression of IRS2, PI31<, Akt mRNA and phosphorylated IRS2, PI3K, Akt protein involved in the canonical PI31</Akt signaling pathway of T2DM rats in liver were significantly up-regulated, while the total IRS2, PI31<, and Akt protein had no obvious changes. Conclusions: The results suggest that Liuwei Dihuang decoction could intervene insulin resistance of T2DM, in part, through regulation of canonical PI3K/Akt signaling pathway of T2DM rats in liver. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
