Wuzang Wenyang Huayu decoction regulates differentially expressed transcripts in the rats' hippocampus after cerebral hypoperfusion.

The modified Wenyang Huayu decoction has been widely used to treat vascular dementia in China for thousands of years. We have previously proved that a modified version, Wuzang Wenyang Huayu decoction has the potential to be a more effective clinical treatment that can attenuate cerebral ischaemic injury. However, the global transcript profile and signalling conduction pathways regulated by this recipe remains unclear. This study established a two-vessel occlusion rat model by bilateral common carotid artery occlusion. Two groups of rats were intragastrically treated Wuzang Wenyang Huayu 2.5 g/kg vs or Piracetam 0.15 g/kg for 2 weeks. Learning and memory abilities were measured with Morris water maze. Neuronal plasticity was observed by HE staining. Differentially expressed transcripts of rat hippocampus were analysed by transcriptomics with Illumina HiSeq2500 platform. Results showed that Wuzang Wenyang Huayu decoction significantly alleviated learning, memory deficits, coordination dysfunction and prevented hippocampus cellular injury; Results further revealed the increased gene expression in KEGG metabolic pathways (MT-ND2. MT-ND3, MT-ND4, MT-ND4L, MT-ND5 and MT-ATP8) and genes involved in signal transduction, carcinogenesis, immune system, endocrine system, nervous system etc (Results further revealed differential expression of genes involved in various systems, including MT-ND2) Our discovery is likely to provide new insights to molecular mechanisms of Wuzang Wenyang Huayu regarding hippocampal transcripts in a murine vascular dementia model.

Astrocyte elevated gene-1 induces autophagy in diabetic cardiomyopathy through upregulation of KLF4.

BACKGROUND: Astrocyte elevated gene-1 (AEG-1), also known as metadherin, 3D3, and lysine-rich carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) coisolated, has emerged as an important oncogene that is overexpressed in a variety of cancers. Previous studies revealed that AEG-1 is also involved in multiple physiological and pathological processes, such as development, inflammation, neurodegeneration, migraine, and Huntington's disease. However, the function of AEG-1 in diabetic cardiomyopathy (DCM) has not been reported yet. Therefore, we conducted this study to characterize the potential role and mechanism of AEG-1 in DCM rats. METHODS: DCM was induced by injections of streptozocin (STZ) in Wistar rats. Rats were randomized to be injected with lentivirus carrying AEG-1 small interfering RNA. Haemodynamic changes of Wistar rats, assessment of cardiac weight index, and the expression of AEG-1 and KLF4 were detected and compared among these three groups. RESULTS: The expressions of AEG-1 and KLF4 in the STZ group were significantly elevated in cardiac tissues compared with the control group. Knockdown of AEG-1 significantly increased the values of left ventricular ejection fraction, ±dp/dt max , repressed autophagy, as well as upregulated the expression of KLF4. CONCLUSIONS: Knockdown of AEG-1 suppresses autophagy in DCM by downregulating the expression of KLF4. This study provide first-notion evidence for the potential value of AEG-1 as a therapeutic target for the treatment of the patients with DCM.

Hypoxic preconditioning improves the survival and neural effects of transplanted mesenchymal stem cells via CXCL12/CXCR4 signalling in a rat model of cerebral infarction.

The treatment of neural deficiency after cerebral infarction is challenging, with limited therapeutic options. The transplantation of mesenchymal stem cells (MSCs) to the ischemic penumbra is a potential therapeutic approach. In the present study, a cerebral infarction model was generated by performing middle cerebral artery occlusion (MCAO) in SD rats. The expression of CXCR4 increased, and the number of MSCs migrating to the peri-infarct area was higher in rats transplanted with preconditioned MSCs than in rats transplanted with untreated MSCs. The rate of apoptosis, as evaluated by TUNEL staining and immunoblotting assays, was reduced in rats receiving preconditioned MSCs. A significant amelioration of neural regeneration and improved neurological function were observed in rats injected with preconditioned MSCs compared with those injected with untreated MSCs. However, the application of an siRNA targeting CXCL12 significantly inhibited the protective role of preconditioned MSCs against apoptosis and promoted the migration of MSCs to the ischemic area, leading to impaired neuronal regeneration and limited recovery of neuronal function. Hypoxic preconditioning of MSCs prior to transplantation suppressed apoptosis and increased their migration abilities, leading to the promotion of neuronal regeneration and improvement in neural function after transplantation. This preconditioning strategy may be considered as a potential approach for the modification of MSCs prior to cell transplantation therapy in patients with cerebral infarction. SIGNIFICANCE OF THE STUDY: We found that hypoxic preconditioning of MSCs improved their ability to promote neuronal regeneration and the recovery of neuronal function. Moreover, we showed that CXCR4 inhibited apoptosis, improved cell homing, and promoted neuronal differentiation, without influencing angiogenesis. Our study provides a relatively safe preconditioning method for potential use for cell transplantation therapy in ischemic cerebral infarction. The results presented here will facilitate the development of novel strategies and techniques to improve the tolerance and migration ability of transplanted cells for the treatment of cerebral infarction sequelae.

The Potential Impact of Radix Paeoniae Alba in Embryonic Development of Mice.

Although Radix Paeoniae Alba (RPA) has been ranked as one of the top 6 herbs used frequently to prevent and treat miscarriages clinically, there is no clear evidence regarding its safety in embryonic development. This study aims to evaluate the potential impacts of RPA on embryonic stem cells (ESCs) and pregnant mice. Cytotoxicity assays of the extract were performed in ESCs and 3T3 cells. Pregnant ICR mice were orally treated with RPA extracts at dosages of 0 (G1 group as negative controls), 2, 8 and 32 g/kg/day (G2, G3 and G4 groups) respectively from the gestation day (Gd) 6-15. On Gd 18, there was no significant difference in the IC50 values between ESCs and 3T3 cells (p > 0.05). There was no significant difference in the maternal and fetal evaluations among four groups (p > 0.05). Fetal IL-2, IL-2r, TNF-α, TNF-αr, IL-4, IL-4r, IL-10r, IL-17 and IL-17r of G4 group were significantly lower than G1 group (p < 0.05). In conclusion, RPA at dosage of 32 g/kg/day (16-folds of human daily dosage) did not cause adverse impact in cultured ESCs and pregnant mice. RPA might down-regulate fetal Th1/Th2/Th17 cytokines and receptors maybe beneficial to embryonic survival and development. Copyright © 2017 John Wiley & Sons, Ltd.

Lower Expression of SPRY4 Predicts a Poor Prognosis and Regulates Cell Proliferation in Colorectal Cancer.

BACKGROUND/AIMS: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Sprouty proteins are modulators of mitogeninduced signal transduction processes and therefore can influence the process of cancerogenesis. The encoded protein of Sprouty homolog 4 (SPRY4) is associated with various human cancers. However, its biological role and clinical significance in CRC development and progression are unknown. METHODS: The aim of this study was to evaluate the expression and biological role of SPRY4 in colorectal cancer. qRT-PCR was performed to investigate the expression of SPRY4 in tumor tissues and corresponding non tumor colorectal tissues from 70 patients. The effect of SPRY4 on proliferation was evaluated by MTT and colony formation assays. CRC cells transfected with SPRY4 were injected into nude mice to study the effect of SPRY4 on tumorigenesis in vivo. RESULTS: The lower expression of SPRY4 was remarkably correlated with deep tumor invasion and advanced TNM stage. Multivariate analyses revealed that SPRY4 expression served as an independent predictor for overall survival. Using 5-aza treatment, we also observed that SPRY4 expression can be affected by DNA methylation. Further experiments revealed that overexpressed SPRY4 significantly inhibited CRC cell proliferation both in vitro and in vivo. CONCLUSION: Our study demonstrated that SPRY4 is involved in the development and progression of colorectal cancer by regulating cell proliferation and shows that SPRY4 may be a potential diagnostic and prognostic target in patients with colorectal cancer.

Impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in stroke patients.

Many studies reported that toll-like receptors (TLRs) played an important role in the process of ischemic stroke (IS). However, the impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in ischemic stroke patients has not yet been reported and was therefore the subject of this study. In this case-control study, a total of 816 ischemic stroke patients and 816 healthy controls were genotyped using Sequenom MassArray technology. The mRNA expression of TLR5 was detected through quantitative real-time PCR among 52 ischemic stroke patients. The levels of IL-1b, IL-6, IL-8, and TNFα were measured by ELISA among 62 IS patients. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined among 816 IS patients using a Hitachi 7600 Automatic Biochemistry Analyzer. Our result showed TLR5 rs5744174 polymorphism was not associated with stroke risk, TLR5 mRNA expression and inflammatory cytokines of IS patients (P > 0.050), but was significantly associated with HDL-C (recessive model: ß = - 0.14, 95 % CI: -0.24 to -0.03, P = 0.009). TLR5 rs5744174 polymorphism may have no impact on the stroke risk, gene expression and inflammatory cytokines, but may influence the HDL-C serum level of IS patients in Chinese Han population.

Analysis of Association between MAP2K4 Gene Polymorphism rs3826392 and IL-1b Serum Level in Southern Chinese Han Ischemic Stroke Patients.

BACKGROUND: Mitogen-activated protein kinase kinase 4 (MAP2K4) gene acts as the direct upstream activator of c-Jun NH2-terminal kinase pathway, which plays an important role in regulating neuron survival and apoptosis in response to cerebral ischemia. However, the association between MAP2K4 gene polymorphisms and ischemic stroke (IS) has not yet been published. Therefore, this study investigates the association between MAP2K4 gene polymorphism rs3826392 and IS susceptibility, as well as its quantitative traits in Southern Chinese Han population. METHODS: A total of 816 Chinese patients with IS and 816 age- and sex-matched controls were recruited. Rs3826392 was genotyped using Sequenom MassARRAY iPLEX platform (Sequenom, San Diego, CA, USA). The mRNA expression of MAP2K4 gene in peripheral blood mononuclear cells was detected using reverse transcription-polymerase chain reaction. The levels of serum cytokines, including IL-1b, IL-6, IL-8, IL-12, and tumor necrosis factor-α (TNF-α), were measured by enzyme-linked immunosorbent assay. RESULTS: Significant association was not observed between MAP2K4 gene polymorphism rs3826392 and IS susceptibility in all genetic models (P > .05). A significant difference was found in IL-1b, IL-6, IL-8, and TNF-α serum levels between patients with IS and control groups. MAP2K4 gene polymorphism rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels compared with AA genotype carriers (P = .029) in patients with IS. CONCLUSION: MAP2K4 gene polymorphism rs3826392 did not contribute to IS susceptibility, but rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels. This result suggests that rs3826392 may play a potential role in the IS inflammatory process.

Global Gene Expression Profile of the Hippocampus in a Rat Model of Vascular Dementia.

Vascular dementia (VD) has been one of the most serious public health problems worldwide. It is well known that cerebral hypoperfusion is the key pathophysiological basis of VD, but it remains unclear how global genes in hippocampus respond to cerebral ischemia-reperfusion. In this study, we aimed to reveal the global gene expression profile in the hippocampus of VD using a rat model. VD was induced by repeated occlusion of common carotid arteries followed by reperfusion. The rats with VD were characterized by deficit of memory and cognitive function and by the histopathological changes in the hippocampus, such as a reduction in the number and the size of neurons accompanied by an increase in intercellular space. Microarray analysis of global genes displayed up-regulation of 7 probesets with genes with fold change more than 1.5 (P < 0.05) and down-regulation of 13 probesets with genes with fold change less than 0.667 (P < 0.05) in the hippocampus. Gene Ontology (GO) and pathway analysis showed that the up-regulated genes are mainly involved in oxygen binding and transport, autoimmune response and inflammation, and that the down-regulated genes are related to glucose metabolism, autoimmune response and inflammation, and other biological process, related to memory and cognitive function. Thus, the abnormally expressed genes are closely related to oxygen transport, glucose metabolism, and autoimmune response. The current findings display global gene expression profile of the hippocampus in a rat model of VD, providing new insights into the molecular pathogenesis of VD.

[Exploration of the Essence of "Endogenous Turbidity" in Chinese Medicine].

The essence of endogenous turbidity in Chinese medicine (CM) is different from cream, fat, phlegm, retention, damp, toxicity, and stasis. Along with the development of modern scientific technologies and biology, researches on the essence of endogenous turbidity should keep pace with the time. Its material bases should be defined and new connotation endowed at the microscopic level. The essence of turbidity lies in abnormal functions of zang-fu organs. Sugar, fat, protein, and other nutrient substances cannot be properly decomposed, but into semi-finished products or intermediate metabolites. They are inactive and cannot participate in normal material syntheses and decomposition. They cannot be transformed to energy metabolism, but also cannot be synthesized as executive functioning of active proteins. If they cannot be degraded by autophagy-lysosome or ubiquitin-prosome into glucose, fatty acids, amino acids, and other basic nutrients to be used again, they will accumulate inside the human body and become endogenous turbidity. Therefore, endogenous turbidity is different from final metabolites such as urea, carbon dioxide, etc., which can transform vital qi. How to improve the function of zang-fu organs, enhance its degradation by autophagy-lysosome or ubiquitin-prosome is of great significance in normal operating of zang-fu organs and preventing the emergence and progress of related diseases.

Association between TNF-δ 238G/A polymorphisms and the risk of ischemic stroke.

BACKGROUND: Stroke is the second highest cause of morbidity and functional disability around the world. In addition, it is the second most common cause of death worldwide [ 1 ]. However, the genetic pathology of stroke is still unclear. Published data on the association between TNF-a 238G/A polymorphisms and ischemic stroke risk are inconsistent and controversial. To provide a more robust estimate about TNF-a 238G/A polymorphisms on the risk of ischemic stroke, we conducted this meta-analysis. METHODS: We used the pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) to investigate the relationship between TNF-α238G/A polymorphisms and ischemic stroke. Publication bias was tested by Begg's test and inverted funnel plot, and Heterogeneity was checked by Cochran's Q statistic and the inconsistency index (I(2)). RESULTS: There are 7 studies that include 1,766 cases and 1,560 controls in this meta-analysis. The results indicated a significant association between TNF-α238G/A polymorphisms and ischemic stroke in overall analysis, Caucasian and Adult. However, statistical association was not observed in Juvenile and Asian. CONCLUSIONS: This meta-analysis suggests that TNF-α238G/A polymorphisms increases the risk of ischemic stroke in Adult, Caucasian, and overall analysis. However, in Juvenile and Asian analysis, significant associations between TNF-α238G/A and ischemic stroke were not found.

Association between the single-nucleotide polymorphism rs12425791 and ischemic stroke in Chinese populations: new data and meta-analysis.

BACKGROUND: Two single-nucleotide polymorphisms rs11833579 and rs12425791 located on chromosome 12p13 were reported to be associated with ischemic stroke in Caucasians. In the present study, we investigated whether the single-nucleotide polymorphism rs12425791 was associated with ischemic stroke in Chinese populations. METHODS: We carried out a case-control study examining a total of 166 Guangxi Han patients with ischemic stroke and 192 healthy controls. We also performed a meta-analysis of the data from our study and those from published studies to investigate whether an association between rs12425791 and ischemic stroke could be detected in Chinese populations. RESULTS: There was no statistically significant association between the single-nucleotide polymorphism rs12425791 and ischemic stroke in the Guangxi Han population. Our meta-analysis also found no significant association between rs12425791 and ischemic stroke in Chinese populations [allelic model odds ratio (OR) = 1.01, 95% confidence interval (CI), 0.96-1.07; dominant model OR = 1.01, 95%CI, 0.94-1.10; recessive model OR = 1.00, 95%CI, 0.86-1.17]. CONCLUSIONS: The single-nucleotide polymorphism rs12425791 does not confer a substantial risk for ischemic stroke in Chinese populations.

Management of hepatic encephalopathy by traditional chinese medicine.

In spite of the impressive progress in the investigation of hepatic encephalopathy (HE), the complex mechanisms underlying the onset and deterioration of HE are still not fully understood. Currently, none of the existing theories provide conclusive explanations on the symptoms that link liver dysfunction to nervous system disorders and clinical manifestations. This paper summarized the diagnostic and therapeutic approaches used for HE in modern medicine and traditional Chinese medicine and provided future perspective in HE therapies from the viewpoint of holistic and personalized Chinese medicine.

Telaprevir for genotype 1 chronic hepatitis C: a systematic review and meta-analysis.

OBJECTIVES: To assess the beneficial and harmful effects of telaprevir for patients with genotype 1 chronic hepatitis C. METHODS: We searched Cochrane Central Register of Controlled Trials (Issue 4, 2012), MEDLINE, EMBASE, Chinese Biomedical Database (CBM), CNKI database and Chinese WanFang Database between 1980 and May 2012. Randomized clinical trials assessing telaprevir in combination with peginterferon alfa and ribavirin versus no intervention or placebo in combination with peginterferon alfa and ribavirin in patients with genotype 1 chronic hepatitis C were included. The primary outcome measure was viral response, including sustained virologic response and virologic response at the end of treatment. The secondary outcome measures were relapse rate, severe adverse events, treatment discontinuation and commonly reported adverse events. RESULTS: Six trials with 2,775 participants were included. Telaprevir in combination with peginterferon alfa and ribavirin seemed to show a significant effect on sustained virologic response, virologic response at the end of treatment and relapse rate in naive patients and previously unsuccessfully treated patients, except T12PR12 which seemed without beneficial effect on sustained virologic response (Odds Ratio (OR) 1.41; 95% CI 0.83 to 2.40) and relapse rate (Odds Ratio (OR) 1.55; 95% CI 0.71 to 3.36) in naive patients. It also was associated with a significantly higher incidence of severe adverse events (Odds Ratio (OR) 2.15, 95% CI 1.29 to 3.58) and treatment discontinuation (Odds Ratio (OR) 4.79, 95% CI 1.72 to 13.37) because of adverse events in previously unsuccessfully treated patients, but not in naive patients. CONCLUSIONS: Telaprevir in combination with peginterferon alfa and ribavirin has been recommended as option for the treatment of genotype 1 chronic hepatitis C. It has been considered as effective to improve viral response and reduce relapse rate in patient who suffer genotype 1 chronic hepatitis C. However, the treatment should be monitored carefully as it may cause some severe adverse events. For further confirmation of its treatment effect and clarify its possible adverse events, more randomized clinical trials need to be carried out.

Ferritin reduction is essential for cerebral ischemia-induced hippocampal neuronal death through p53/SLC7A11-mediated ferroptosis.

Cerebral ischemia is the most common cause of hippocampal neuronal death and the most prevalent cause of stroke with high mortality rate. Ferroptosis has been suggested to affect the role of hippocampal neurons. This study explores the influence of lentivirus infection-induced ferritin overexpression in hippocampal neuronal injury and death through simulations in August Copenhagen Irish rat models. Twenty-four-hour cerebral ischemia-reperfusion injury was induced in the rats after 90-min middle cerebral artery occlusion (MCAO). Ferritin overexpression was induced through lentivirus infection. The Morris Water Maze (MWM) test and tau hyperphosphorylation test were performed on hippocampal neurons to establish a MCAO model. The effect of ferritin overexpression on hippocampal neuronal death was evaluated using hematoxylin-eosin staining and annexin V/propidium iodide flow cytometry. The MWM test revealed that MCAO modeling decreased the cognitive and locomotor capacity of the rats, whereas ferritin overexpression partially reversed the effect of MCAO. In addition, the hyperphosphorylation of tau caused by MCAO was reduced by ferritin. Pathogenic changes, impaired viability, increased apoptosis, and elevated caspase-9 cleavage in hippocampal neurons were clearly recovered by ferritin. Moreover, robust reactive oxygen species production and glutathione consumption, which was induced by MCAO modeling, were ameliorated by ferritin. Furthermore, two key modulators of ferroptosis, p53 and SLC7A11, were demonstrated to be upregulated by MCAO modeling and downregulated by ferritin. Ferritin reduction is essential for cerebral ischemia-induced hippocampal neuronal ferroptosis mediated via p53 and SLC7A11.

MicroRNA-107 Ameliorates Damage in a Cell Model of Alzheimer's Disease by Mediating the FGF7/FGFR2/PI3K/Akt Pathway.

Alzheimer's disease (AD), the most prevalent representation of dementia, is a neurodegenerative disease resulting from the degenerative disturbance of the central nervous system. Previous studies have indicated that miR-107 is reduced in the brain neocortex of patients with AD; however, its underlying mechanism is not clear. Therefore, the objective of this study was to explore the question of whether miR-107 participates in AD development. The study confirmed that the miR-107 expression levels were dramatically decreased in patients with AD and in beta-amyloid (Aß) (Aß)-treated SH-SY5Y cells compared with control groups. Upregulation of miR-107 reversed the inhibitory role of Aß on cell proliferation and viability. In addition, miR-107 upregulation also ameliorated the Aß-induced inflammation and apoptosis of SH-SY5Y cells. Furthermore, using bioinformatic prediction, dual-luciferase reporter assay (DLRA), quantitative polymerase chain reaction (qPCR), and Western blot (WB), miR-107 was confirmed to reduce the expression level of FGF7, and it subsequently deactivated the FGFR2/PI3K/Akt pathway. Moreover, FGF7 overexpression counteracted the role of miR-107 in the viability, proliferation, inflammation, and apoptosis of Aß-induced SH-SY5Y cells.

[Mechanism of catgut embedding at back-shu points for nonalcoholic steatohepatitis based on IKK/IKB/NF-κB signaling pathway].

OBJECTIVE: To explore the mechanism of catgut embedding at back-shu points on nonalcoholic steatohepatitis (NASH) in rats based on IKK/IKB/NF-κB signaling pathway and downstream inflammatory factors. METHODS: Eighty SPF SD rats were selected, among them 10 rats were selected divided into a normal group (group A), and the remaining 70 rats were fed with high-fat diet to establish NASH model. At the end of 12 weeks, 10 rats were randomly selected to verify whether the model establishment was successful. Then the remaining 60 rats were randomly divided into a model group (group B), a catgut embedding at back-shu points group (group C), a catgut embedding at abdominal points group (group D), an acupuncture at back-shu points group (group E), a sham catgut embedding group (group F) and a western medication group (group G), 10 rats in each group. The rats in the group C were treated with catgut embedding at "Ganshu" (BL 18), "Pishu" (BL 20), "Weishu" (BL 21) and "Shenshu" (BL 23); the rats in the group D were treated with catgut embedding at "Daheng" (SP 15), "Fujie" (SP 14), "Huaroumen" (ST 24) and "Tianshu" (ST 25); the rats in the group E were treated with acupuncture at the same acupoints as the group C; the rats in the group F were treated with catgut embedding at back-shu points but the needle did not enter subcutaneous tissue gamma; the rats in the group G were treated with intragastric administration of vitamin E capsule. All the treatment was given for 4 weeks. The rats in the group A were fed with normal diet until the end of 16 weeks without any intervention. The rats in the group B continued to be fed with high-fat diet until the end of 16 weeks. After the intervention, the liver index was calculated; the liver histomorphology was observed by HE staining; the liver function [alanine aminotransferase (ALT), gamma glutamyl transferase (γ-GGT), alkaline phosphatase (ALP)] and blood lipid [serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL)] were measured by serum biochemistry. The serum levels of TNF-α, IL-6 and IL-1ßwere detected by ELISA, and the expressions of IKK-α, NF-κBp65, IL-6, IL-1ß and TNF-α proteins in liver tissue were detected by Western blot. The temperature of the conception vessel and the governor vessel was measured by infrared thermography. RESULTS: Compared with the group A, the obvious steatosis and inflammatory cell infiltration were observed in the group B, and the body weight, liver wet-weight and liver index were all increased (P<0.01). Compared with the group B, the liver tissue morphology in the group C, the group D, the group E and the group G was improved in varying degrees, and the liver index was decreased (P<0.05), which was the most significant in the group C (P<0.05). Compared with the group A, the ALT, γ-GGT, ALP, TG, TC, LDL, TNF-α, IL-6 and IL-1ß were all increased in the group B (P<0.01); compared with the group B, the ALT, γ-GGT, ALP, TG, TC, LDL, TNF-α, IL-6 and IL-1ß in all intervention groups were all decreased in varying degrees (P<0.01, P<0.05), which was the most significant in the group C (P<0.01). Compare with the group A, the expressions of IKK-α, NF-κBp65, TNF-α, IL-6 and IL-1ßproteins in the group B were all increased (P<0.01); compared with the group B, the expressions of IKK-α, NF-κBp65, TNF-α, IL-6 and IL-1ßproteins in all intervention groups were decreased in varying degrees (P<0.05), which was the most significant in the group C (P<0.01). Compared with the group A, the temperature of the conception vessel and governor vessel was decreased in the group B (P<0.01). Compared with the group B, the temperature of the conception vessel and governor vessel was all increased in the group C, the group D and the group E (P<0.01); the temperature of the conception vessel in the group C was similar to that in the group D (P>0.05), while the temperature of the governor vessel in the group C was superior to that in the group D (P<0.05). CONCLUSION: The catgut embedding at back-shu points might inhibit the activation of IKK/IKB/NF-κB signaling pathway to interrupt the inflammatory cascade, and reduce the "second hit" of inflammatory factors on liver, which could slow down NASH progress and prevent and treat NASH.

Inhibitory Effect of Semen Litchi Drug Serum on the Proliferation of Human Hepatoma HepG2 Cells and Expression of VEGF and MMP-9.

OBJECTIVE: To investigate inhibitory effect of semen litchi drug serum on proliferation of human hepatoma HepG2 cells and its effect on the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9). STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: College of Pharmacy, Guangxi University of Chinese Medicine, China, from June 2017 to January 2018. METHODOLOGY: Semen litchi drug serum with concentrations of 0 mg/kg (control group), 3 g/kg (low dose group), 6 g/kg (medium dose group) and 12 g/kg (high dose group) was used to act on HepG2 cells at the logarithmic phase. Inhibitory effect of semen litchi drug serum on cell growth, expression of VEGF and MMP-9 mRNA and protein was detected. RESULTS: Inhibitory effect of semen litchi drug serum on the proliferation of HepG2 cells significantly increased with the increase of drug concentration, which was dose-time dependent. Expression levels of VEGF and MMP-9 mRNA in HepG2 cells after 48 hours of treatment by semen litchi low-dose group, medium-dose group, and high-dose group were lower than those in control group (all p <0.001). After acting on HepG2 cells for 48 hours, relative expressions of VEGF and MMP-9 protein in semen litchi low-dose group, medium-dose group, and high-dose group were lower than those in control group (all p<0.001). CONCLUSION: Semen litchi drug serum can inhibit proliferation of hepatoma cells in vitro. The anti-hepatoma effect of semen litchi drug serum may be exerted through down-regulating the expression of VEGF and MMP-9 and inhibiting angiogenesis of hepatocellular carcinoma.

Effect of Astragalus Polysaccharide on the Expression of VEGF and EGFR in Mice with Lewis Transplantable Lung Cancer.

The aim of this study was to determine the effect of Astragalus polysaccharide (APS) on the expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in mice with Lewis transplantable lung cancer. It was an experimental study carried out from June 2017 to January 2018 at the College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China. Forty male SPF-level C57BL/6J mice were selected and inoculated with Lewis lung cancer cell suspension in the right axilla of the mice to establish a lung-cancer mouse model. The mice were randomly divided into a model control group and APS groups with high, middle and low dosages, respectively, 10 in each group. After inoculation of Lewis tumor cell suspension for 2 days, mice in the model control group were injected intraperitoneally with 50 mL/kg of 0.9% sodium chloride solution, whereas, mice in the APS groups with high, middle and low dosages were intraperitoneally injected with APS at 100, 50, 25 mg/kg, respectively. The research results showed that APS can effectively inhibit the growth and metastasis of Lewis lung cancer in mice, improve immune organ function, inhibit the protein expression of VEGF and EGFR in tumor tissues, and have a concentration-effect relationships.

TGF-ß1 Restores Hippocampal Synaptic Plasticity and Memory in Alzheimer Model via the PI3K/Akt/Wnt/ß-Catenin Signaling Pathway.

Alzheimer's disease (AD) is the most common neurodegenerative disturbances. Dysfunction of synaptic plasticity and decline in cognitive functions are the most prominent features of AD, but the mechanisms of pathogenesis have not been well elucidated. In this paper, transforming growth factor-ß1 (TGF-ß1) was found to be reduced in the hippocampus of AD mouse which was accompanied by impaired pine density, synaptic plasticity, and memory function. Hippocampal injection of TGF-ß1 rescued the AD-induced memory function impairment. In addition, TGF-ß1 ameliorated synaptic plasticity and increased synaptic plasticity-associated protein expression including Arc, NR2B, and PSD-95 in mouse model of AD. Furthermore, we demonstrated that Akt/Wnt/ß-catenin pathway protein expression in the hippocampus was suppressed in a mouse model of AD and TGF-ß1 significantly enhanced the phosphorylation Akt, GSK3ß, and increased the nuclear ß-catenin. These results indicate that TGF-ß1activates PI3K/Akt/Wnt/ß-catenin signaling in mouse model of AD, which is important for promoting synaptic plasticity related to memory function. More importantly, suppression of PI3K/Akt/Wnt/ß-catenin pathway compromised the beneficial effects of TGFß1 in Alzheimer's model. Hence, TGF-ß1 shows protective effect on neurons, which might be through the PI3K/Akt/Wnt/ß-catenin signaling pathway, serving as a potential target in AD pathology.

Observation of the effect of bone marrow mesenchymal stem cell transplantation by different interventions on cirrhotic rats.

Bone marrow mesenchymal stem cells (BMSCs) transplantation has attracted attention for the treatment of liver cirrhosis and end-stage liver diseases. Therefore, in this study, we evaluated the effect of different methods of BMSCs transplantation in the treatment of liver cirrhosis in rats. Seventy-two male Sprague-Dawley rats were divided into 7 groups: 10 were used to extract BMSCs, 10 were used as normal group, and the remaining 52 rats were randomly divided into five groups for testing: control group, BMSCs group, BMSCs+granulocyte colony-stimulating factor (G-CSF) group, and BMSCs+Jisheng Shenqi decoction (JSSQ) group. After the end of the intervention course, liver tissue sections of rats were subjected to hematoxylin and eosin (H&E) and Masson staining, and pathological grades were scored. Liver function [aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB)] and hepatic fibrosis markers [hyaluronidase (HA), laminin (LN), type III procollagen (PCIII), type IV collagen (CIV)] were measured. BMSCs+JSSQ group had the best effect of reducing ALT and increasing ALB after intervention therapy (P<0.05). The reducing pathological scores and LN, PCIII, CIV of BMSCs+G-CSF group and BMSCs+JSSQ group after intervention therapy were significant, but there was no significant difference between the two groups (P>0.05). The effect of JSSQ on improving stem cell transplantation in rats with liver cirrhosis was confirmed. JSSQ combined with BMSCs could significantly improve liver function and liver pathology scores of rats with liver cirrhosis.