Protective Effects of Kaempferitrin on Advanced Glycation End Products Induce Mesangial Cell Apoptosis and Oxidative Stress.

Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) both play important roles in diabetic nephropathy (DN). Previous studies have identified glomerular mesangial cells (GMCs) injury as a key early risk factor in the development of DN. Kaempferitrin (KM) is a potent antioxidant with hypoglycemic action. Although KM is known to protect against AGE-induced damage in GMCs, the effects and the mechanisms by which they occur are poorly understood. In this study, cultured rat GMCs were exposed to AGE-induced oxidative stress (OS) to model DN in vitro. Reactive oxygen species (ROS) was analyzed by 2',7'-dichlorofluorescin diacetate (DCFH-DA). Superoxide dismutase (SOD) and malondialdehyde (MDA) were studied using commercial kits. Mitochondrial membrane potential (Δψm) was measured by rhodamine 123. Hoechst 33258 and annexin V and propidium iodide (PI) double staining were performed to observe the apoptosis states in GMCs, whereas apoptosis and protective mechanism in AGE-induced GMCs were investigated by Western blot. The data revealed that KM effectively increased SOD activity, decreased MDA levels, suppressed ROS generation, and protected against OS in AGE-induced GMCs. Treatment with KM also inhibited the expression of collagen IV and transforming growth factor-ß1 (TGF-ß1), improved mitochondrial membrane potential recovery, and suppressed the mitochondrial/cytochrome c-mediated apoptosis pathway through the expression of anti-apoptotic factors in GMCs in vitro. These findings suggest that KM may be a new potential agent in the treatment of DN in future.

Differences in spatial and temporal frequency interactions between central and peripheral parts of the feline area 18.

The visual system demonstrates significant differences in information processing abilities between the central and peripheral parts of the visual field. Optical imaging based on intrinsic signals was used to investigate the difference in stimulus spatial and temporal frequency interactions related to receptive field eccentricity in the cat area 18. Changing either the spatial or the temporal frequency of grating stimuli had a significant impact on responses in the cortical areas corresponding to the centre of the visual field and more peripheral parts at 10 degrees eccentricity. The cortical region corresponding to the centre of the gaze was tuned to 0.4 cycles per degree (c/deg) for spatial frequency and 2 Hz for temporal frequency. In contrast, the cortical region corresponding to the periphery of the visual field was tuned to a lower spatial frequency of 0.15 c/deg and a higher temporal frequency of 4 Hz. Interestingly, when we simultaneously changed both the spatial frequency and the temporal frequency of the grating stimuli, the responses were significantly different from those estimated with an assumption of independence between the spatial and temporal frequency in the cortical region corresponding to the periphery of the visual field. However, in the cortical area corresponding to the centre of the gaze, spatial frequency showed significant independence from temporal frequency. These properties support the notion of relative specialization of visual information processing for peripheral representations in cortical areas.

CC chemokine ligand 18(CCL18) promotes migration and invasion of lung cancer cells by binding to Nir1 through Nir1-ELMO1/DOC180 signaling pathway.

Non-small cell lung cancer (NSCLC) comprises nearly 80% of lung cancers and the poor prognosis is due to its high invasiveness and metastasis. CC chemokine ligand 18 (CCL18) is predominantly secreted by M2-tumor associated macrophages (TAMs) and promotes malignant behaviors of various human cancer types. In this study, we report that the high expression of CCL18 in TAMs of NSCLC tissues and increased expression of CCL18 in TAMs is correlated with the lymph node metastasis, distant metastasis, and poor prognosis NSCLC patients. CCL18 can increase the invasive ability of NSCLC cells by binding to its receptor Nir1. In addition, CCL18 is capable of modulating cell migration and invasion by regulating the activation of RAC1 which resulted in cytoskeleton reorganization in an ELMO1 dependent manner. Furthermore, we found that CCL18 could enhance adhesion of NSCLC cells via activating ELMO1-integrin ß1 signaling. Thus, CCL18 and its downstream molecules may be used as targets to develop novel NSCLC therapy. © 2016 Wiley Periodicals, Inc.

Integrated network pharmacology and pharmacological investigations to discover the active compounds of Toona sinensis pericarps against diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Toona sinensis (A. Juss.) Roem. Is a deciduous woody plant native to Eastern and Southeastern Asia. Different parts of this plant have a long history of being applied as traditional medicines to treat various diseases. The fruits have been used for antidiabetic, antidiabetic nephropathy (anti-DN), antioxidant, anti-inflammatory, and other activities. AIM OF THE STUDY: The purpose of this study was to investigate the effects of EtOAc (PEAE) and n-BuOH extracts (PNBE) from T. sinensis pericarps (TSP) on kidney injury in high-fat and high-glucose diet (HFD)/streptozotocin (STZ)-induced DN mice by network pharmacology and pharmacological investigations, as well as to further discover active compounds that could ameliorate oxidative stress and inflammation, thereby delaying DN progression by regulating the Nrf2/NF-κB pathway in high glucose (HG)-induced glomerular mesangial cells (GMCs). MATERIALS AND METHODS: The targets of TSP 1-16 with DN were analyzed by network pharmacology. HFD/STZ-induced DN mouse models were established to evaluate the effects of PEAE and PNBE. Six groups were divided into normal, model, PEAE100, PEAE400, PNBE100, and PNBE400 groups. Fasting blood glucose (FBG) levels, organ indices, plasma MDA, SOD, TNF-α, and IL-6 levels, as well as renal tissue Nrf2, HO-1, NF-κB, TNF-α, and TGF-ß1 levels were determined, along with hematoxylin-eosin (H&E) and immunohistochemical (IHC) analysis of kidney sections. Furthermore, GMC activity screening combined with molecular docking was utilized to discover active compounds targeting HO-1, TNF-α, and IL-6. Moreover, western blotting assays were performed to validate the mechanism of Nrf2 and NF-κB in HG-induced GMCs. RESULTS: Network pharmacology predicted that the main targets of PEAE and PNBE in the treatment of DN include IL-6, INS, TNF, ALB, GAPDH, IL-1ß, TP53, EGFR, and CASP3. Additionally, major pathways include AGE-RAGE and IL-17. In vivo experiments, treatment with PEAE and PNBE effectively reduced FBG levels and organ indices, while plasma MDA, SOD, TNF-α, and IL-6 levels, renal tissue Nrf2, HO-1, NF-κB, TNF-α, and TGF-ß1 levels, and renal function were significantly improved. PEAE and PNBE significantly improved glomerular and tubule injury, and inhibited the development of DN by regulating the levels of oxidative stress and inflammation-related factors. In vitro experiments, compound 11 strongly activated HO-1 and inhibited TNF-α and IL-6. The molecular docking results revealed that compound 11 exhibited a high binding affinity towards the targets HO-1, TNF-α, and IL-6 (<-6 kcal/mol). Western blotting results showed compound 11 effectively regulated Nrf2 and NF-κB p65 protein levels, and significantly improved oxidative stress damage and inflammatory responses in HG-induced GMCs. CONCLUSION: PEAE, PNBE, and their compounds, especially compound 11, may have the potential to prevent and treat DN, and are promising natural nephroprotective agents.

Objective assessment of the association between telomere length, a biomarker of aging, and health screening indicators: A cross-sectional study.

Physical examination data are used to indicate individual health status and organ health, and understanding which physical examination data are indicative of physiological aging is critical for health management and early intervention. There is a lack of research on physical examination data and telomere length. Therefore, the present study analyzed the association between blood telomere length and physical examination indices in healthy people of different ages to investigate the role and association of various organs/systems with physiological aging in the human body. The present study was a cross-sectional study. Sixteen physical examination indicators of different tissue and organ health status were selected and analyzed for trends in relation to actual age and telomere length (TL). The study included 632 individuals with a total of 11,766 data for 16 physical examination indicators. Age was linearly correlated with 11 indicators. Interestingly, telomere length was strongly correlated only with the renal indicators eGFR (P < .001), CYS-C (P < .001), and SCR (P < .001). The study established that renal aging or injury is a risk factor for Physical aging of the human body. Early identification and management are essential to healthcare.

Systemic knockout of Tmem175 results in aberrant differentiation but no effect on hematopoietic reconstitution.

Lysosomes play crucial roles in regulating cell metabolism, and K+ channels are critical for controlling various aspects of lysosomal function. Additionally, lysosomal activity is essential for maintaining the quiescence of hematopoietic stem cells (HSCs) under both steady-state and stress conditions. Tmem175 is a lysosomal potassium channel protein. To further investigate the role of K+ channels in HSCs, our study employed knockout mice to examine the function of Tmem175. Our research findings demonstrate that the deletion of Tmem175 does not disrupt the functionality of HSCs in both stable and stressed conditions, including irradiation and intraperitoneal 5-FU injections. However, we did observe that the absence of Tmem175 impairs the long-term differentiation capacity of HSCs into myeloid differentiated subpopulation cells（In this paper, it is referred to simply as M cells）in HSC transplantation test, while promoting their differentiation into T cells. This suggests that Tmem175 plays a role in the lineage differentiation of HSCs without being essential for their self-renewal or long-term regenerative capabilities.

Mechanism of oxymatrine in the treatment of cryptosporidiosis through TNF/NF-κB signaling pathway based on network pharmacology and experimental validation.

Cryptosporidiosis is a worldwide zoonotic disease. Oxymatrine, an alkaloid extracted and isolated from the plant bitter ginseng, has been reported to have therapeutic effects on cryptosporidiosis. However, the underlying mechanism of its action remains unclear. In this study, we utilized network pharmacology and experimental validation to investigate the mechanism of oxymatrine in the treatment of cryptosporidiosis. First, the potential targets of drugs and diseases were predicted by TCMSP, Gene Cards, and other databases. Following the intersection of drug-disease targets, the DAVID database was used to implement the enrichment analysis of GO functions and KEGG pathways, and then the network diagram of "intersected target-KEGG" relationship was constructed. Autodock 4.2.6 software was used to carry out the molecular docking of core targets to drug components. Based on the establishment of a mouse model of cryptosporidiosis, the validity of the targets in the TNF/NF-κB signaling pathway was confirmed using Western blot analysis and Quantitative Rea-ltime-PCR. A total of 41 intersectional targets of oxymatrine and Cryptosporidium were generated from the results, and five core targets were screened out by network analysis, including RELA, AKT1, ESR1, TNF, and CASP3. The enrichment analysis showed that oxymatrine could regulate multiple gene targets, mediate TNF, Apoptpsis, IL-17, NF-κB and other signaling pathways. Molecular docking experiments revealed that oxymatrine was tightly bound to core targets with stable conformation. Furthermore, we found through animal experiments that oxymatrine could regulate the mRNA and protein expression of IL-6, NF-κB, and TNF-α in the intestinal tissues of post-infected mice through the TNF/NF-κB signaling pathway. Therefore, it can be concluded that oxymatrine can regulate the inflammatory factors TNF-α, NF-κB, and IL-6 through the TNF/NF-κB signaling pathway for the treatment of cryptosporidiosis. This prediction has also been validated by network pharmacology and animal experiments.

Gab2 expression in glioma and its implications for tumor invasion.

Gliomas are characterized by high invasiveness and poor prognosis. Better understanding of the mechanism of invasion in glioma cells is essential to the design of effective therapy. Recently Grb2-associated binder 2 (Gab2), a member of the DOS/Gab family of scaffolding adapters, has been reported to play important roles in the development and progression of human cancers. However, it is not known whether Gab2 has any role in the migration and invasion of gliomas. This study attempts to investigate the association between Gab2 expression and progression of gliomas and the molecular mechanism of Gab2 in the glioma cell invasion. Methods. The expression of Gab2 in pairs of matched glioma tissues and their normal brain tissues was detected by Western blot. Immunohistochemistry was applied to evaluate the expression of Gab2 in 163 cases of histologically diagnosed gliomas. The invasive character of Gab2 decreased glioma cells and control glioma cells were investigated in vitro and in vivo in SCID mice brain. Results. Gab2 is found to be high expressed in gliomas and a subset of cancer cell lines. Statistical analysis suggested that the up-regulation of Gab2 correlated with the WHO grade of gliomas (p < 0.01) and that patients with high Gab2 expression levels exhibited shorter survival time (p < 0.01). In an animal experiment, knockdown of Gab2 through siRNA inhibited invasive ability of glioma cells into the brain of SCID mice. In cell research, reduction of Gab2 by siRNA inhibits the migration and invasion of glioma cells by mediating cytoskeleton rearrangement and MMPs expression. Additionally, IGF-1-induced pAkt and pmTOR phosphorylation was suppressed by the knockdown of Gab2. Conclusion. Gab2 may be a useful prognostic marker for gliomas and a novel therapeutic target for glioma invasion intervention.

Relatlimab: a novel drug targeting immune checkpoint LAG-3 in melanoma therapy.

Relatlimab is a type of human immunoglobulin G4 monoclonal blocking antibody. It is the world's first Lymphocyte-Activation Gene-3 (LAG-3) inhibitor and the third immune checkpoint inhibitor with clinical application, following PD-1 and CTLA-4. Relatlimab can bind to the LAG-3 receptor which blocks the interaction between LAG-3 and its ligand to reduce LAG-3 pathway-mediated immunosuppression and promote T-cell proliferation, inducing tumor cell death. On 18 March 2022, the U.S. FDA approved the fixed-dose combination of relatlimab developed by Bristol Myers Squibb with nivolumab, under the brand name Opdualag for the treatment of unresectable or metastatic melanoma in adult and pediatric patients aged 12 and older. This study comprehensively describes the mechanism of action and clinical trials of relatlimab and a brief overview of immune checkpoint drugs currently used for the treatment of melanoma.

Does Confucian culture affect public service motivation of grassroots public servants? Evidence from China.

Public service motivation contains distinctive cultural characteristics. Different cultural backgrounds shape public service motives with different connotations and levels. However, the traditional cultural values rooted in historical development and socialization process have not received enough attention in the research on public service motivation. In order to investigate the influence of Confucian culture based on Chinese scenes on public service motivation, in the current study we collected 1308 representative questionnaires from 12 cities in central and eastern China, and adopted the dual fixed effect model and moderating effect model to verify six hypotheses. The empirical results showed that Confucian culture has different effects on public service motivation from four dimensions, namely, attraction to politics and policy making (APP), commitment to public interest (CPI), compassion (COM), and self-sacrifice (SS). The paternalistic leadership plays a part in moderating the influence of Confucian culture on public service motivation. This study not only expands the cross-cultural applicability of the theory of public service motivation in non-western countries, but also supplements the evidence of research on public service motivation in East Asian countries. In practice, it is necessary for the organizations to consider the importance of specific cultural values for organizational culture and personal value orientation.

[Deficiency of water channel AQP4 aggravates NMDA-induced brain injury in mice].

OBJECTIVE: To evaluate the role of water channel AQP4 in NMDA-induced brain injury in mice. METHODS: In AQP4 gene knockout (AQP4(-/-)) mice, brain injury was induced by microinjection of NMDA into the cortex. The injured area was determined by toluidine blue staining, degenerated neurons were detected by Fluro-Jade B staining, and increased blood-brain barrier (BBB) permeability was evaluated by IgG immunostaining. RESULT: Compared with wild-type mice, AQP4(-/-) mice exhibited increased cortical lesion area, aggravated neuron degeneration, and increased BBB disruption after NMDA microinjection. CONCLUSION: AQP4 may play a protective role in NMDA-induced brain injury in mice.

[Rotenone-induced changes of cysteinyl leukotriene receptor 1 expression in BV2 microglial cells].

OBJECTIVE: To prepare and identify a polyclonal antibody (pAb) against (mouse) cysteinyl leukotriene receptor 1 (CysLT(1)) and to investigate the changes of CysLT(1) receptor expression in BV2 microglial cells after rotenone treatment. METHODS: Rabbits were immunized with KLH-coupled CysLT(1) peptide to prepare the pAb. The titer of the pAb in rabbit plasma was detected by ELISA method, and the specificity of the pAb was tested by antigen blockade. After BV2 cells were treated with rotenone (0.01-1 µmol/L) for 24 h, the expression of CysLT(1) was determined by immunostaining, Western blotting and RT-PCR. RESULT: The pAb showed a titer of 1/32728, and was not cross-reacted with antigens of CysLT(2) receptor and GPR17. Immunostaining, Western blotting and RT-PCR analysis showed the expression of CysLT(1) receptor in BV2 microglia. Rotenone at 1µmol/L significantly induced an increased expression of CysLT(1) receptor. CONCLUSION: The prepared CysLT(1) receptor polyclonal antibody has a high titer and high specificity to meet testing requirements of Western blotting and immunostaining; CysLT(1) is associated with rotenone-induced injury of BV2 microglial cells.

[Preparation and identification of a polyclonal antibody against novel cysteinyl leukotriene receptor GPR17].

OBJECTIVE: To prepare and identify a polyclonal antibody (pAb) against GPR17, a novel cysteinyl leukotriene receptor. METHODS: Rabbits were immunized with KLH-coupled GPR17 peptide to prepare the pAb. The titer of the pAb in rabbit plasma was detected by indirect ELISA, and the specificity of the pAb was tested by antigen blockade. GPR17 tissue distribution was detected by Western blot with the pAb. RESULTS: The pAb showed a titer as high as 1:16 364,and was not cross-reacted with the antigens of CysLT(1) and CysLT(2) receptors. A higher expression of GPR17 in the rat brain and heart was detected using the newly prepared pAb. The molecular weigh of GPR17 protein was about 43 kD. CONCLUSION: The prepared GPR17 pAb has high sensitivity and specificity,and can be used in Western blot for detecting GPR17.

[Preparation and identification of polyclonal antibody against cysteinyl leukotriene receptor 2].

OBJECTIVE: To prepare and identify a polyclonal antibody against cysteinyl leukotriene receptor (CysLT(2)receptor). METHODS: Rabbits were immunized with KLH-coupled CysLT(2) receptor peptide to prepare the polyclonal antibody (pAb). The titer of the pAb in rabbit plasma was detected by indirect ELISA, and the specificity of the pAb was tested by antigen blockade. The tissue distribution of CysLT(2) receptor was detected by Western blot and immunohistochemistry with the prepared pAb. RESULT: The pAb showed a titer higher than 1/1047296, and was specific to CysLT(2) receptor, without cross-reaction with the antigens of CysLT(1) receptor and GPR17. A higher expression of CysLT(2) receptor in kidney, brain and lung of rats and mice was detected by Western blot analysis using the prepared pAb. The molecular weight of CysLT(2) receptor protein was about 40 kD. Immunohistochemical examination showed that CysLT(2) receptor was expressed mainly in the neuron, and partly in astrocytes in rat brain. CONCLUSION: The prepared CysLT(2) receptor pAb has high sensitivity and specificity, and can be used in Western blot and immunohistochemistry.

[Effect of QTY06 on lipopolysaccharide-induced chronic airway inflammation and MUC5ac secretion in rats].

OBJECTIVE: To investigate the effect of synthetic drug QTY06 on chronic airway inflammation and mucoprotein expression induced by intratracheal (i.t) instillation of lipopolysaccharide (LPS). METHODS: Chronic airway inflammation was induced by i.t instillation of LPS in rats. Phospholipids content and the number of leucocytes in bronchoalveolar lavage fluid (BALF), pathological and immunochemical changes were examined 3 weeks after LPS instillation. The effect of QTY06 on chronic airway inflammation was observed. RESULT: After treatment with QTY06, phospholipids in BALF was significantly increased, and the percentages of neutrophils and lymphocytes were decreased as well as the total number of leucocytes. Compared with the model group, pathological examination showed that tracheitis, bronchitis and pulmonary interstitial inflammation in QTY06 groups were significantly attenuated; epithelial damage was alleviated, infiltration of inflammatory cells reduced and the number of goblet cells decreased. QTY06 significantly decreased MUC5ac expression in trachea and bronchiole epithelium, and reduced the optical density and mucins area (%) as detected by image analysis in rats with chronic airway inflammation. CONCLUSION: QTY06 can reduce and inhibit the chronic airway inflammation induced by LPS in rats, and increase the content of phospholipids in pulmonary surfactant and inhibit the hypersecretion of airway mucins.

[Effect of Spearmint oil on inflammation, oxidative alteration and Nrf2 expression in lung tissue of COPD rats].

OBJECTIVE: To investigate the effect of Spearmint oil on inflammation, oxidative alteration and Nrf2 expression in rats with chronic obstructive pulmonary disease(COPD). METHODS: COPD model was induced by intratracheal instillation of Klebsiella pneumonia and lipopolysaccharide (LPS) for 12 weeks in rats, and COPD rats were treated with Spearmint oil for 3 weeks. After COPD was induced, the pathological changes, changes in leucocyte number in blood and bronchoalveolar lavage fluid (BALF), MDA in lung homogenate and Nrf2 expression were observed. The effects of Spearmint oil on these changes were determined. RESULT: Spearmint oil 100 mg*kg(-1)significantly reduced leucocyte numbers in BALF, and attenuated bronchiolitis, pulmonary interstitial inflammation and inflammation cell infiltration. Spearmint oil 30-300 mg*kg(-1)decreased the destruction of pulmonary alveolus and the thickness of bronchioles walls, and inhibited goblet cell proliferation. Spearmint oil significantly reduced MDA in lung homogenate, and decreased the expression of Nrf2 protein in lung tissues. CONCLUSION: Spearmint oil has protective effect on lung injury in COPD rats, since it improves pulmonary inflammation,oxidative alteration, and enhances Nrf2 protein expression.

Long-term Object Discrimination at Several Viewpoints Develops Neural Substrates of View-invariant Object Recognition in Inferotemporal Cortex.

Object recognition requires differentiation across different objects and generalization across views of the same object. We previously demonstrated that discrimination of object images at several views without any possibility of association was enough to achieve object recognition within a certain range of viewing angles and confirmed the response tolerance of monkey inferotemporal cells within a similar range of viewing angles. However, neither behavioral object recognition nor electrophysiological response tolerance was complete across views. In the present study, we extended such learning past performance saturation and recorded neuronal activity during the further learning period. When monkeys were trained to discriminate objects at several views, we found that they could discriminate the trained objects regardless of the eventual change in viewing angle, and confirmed a response tolerance at the population level over a large viewing angle range covering all the viewpoints experienced. At the cell population level, such overtraining leads to significantly higher neural response similarity for views of the same objects than for views of different objects regardless of the extent of viewing angle separation. These results suggest a possible method of view-invariant object recognition development.

Autocrine IL-8 promotes F-actin polymerization and mediate mesenchymal transition via ELMO1-NF-κB-Snail signaling in glioma.

Glioma is the most common form of primary malignant brain cancers. Tumor cell invasiveness is a critical challenge in the clinical management of glioma patients. The invasive biological feature of glioma cell is stimulated by both autocrine and paracrine factors including chemokine IL-8. In this study, we report that the production of IL-8 is higher in glioma tissues and cells than adjacent nontumor tissues (ANT) and normal glial cells. Autocrine IL-8 can increase the invasive ability of glioma cells by binding to CXCR1. In addition, high expression of IL-8 indicates poor prognosis of glioma patients. Furthermore, IL-8 is capable of modulating cell migration and invasion by regulating the activation of RAC1 which resulted in cytoskeletal reorganisation in an ELMO1 dependent manner. Finally, we found that IL-8 could enhance mesenchymal transition(MT) of glioma cells by activating ELMO1-NF-κB-Snail signaling. Our data indicate that IL-8 autocrine is responsible for the invasive phenotype of glioma and IL-8 may be a useful prognostic marker for glioma and novel therapeutic target for glioma invasion intervention.

1,8-cineol attenuates LPS-induced acute pulmonary inflammation in mice.

Eucalyptol, also known as 1,8-cineol, is a monoterpene and has been shown to exert anti-inflammatory and antioxidant effect. It is traditionally used to treat respiratory disorders due to its secretolytic properties. In the present study, we evaluated the effect of 1,8-cineol on pulmonary inflammation in a mouse model of acute lung injury. We found that 1,8-cineol significantly decreased the level of TNF-α and IL-1ß, and increased the level of IL-10 in lung tissues after acute lung injury induced by lipopolysaccharide (LPS). It also reduced the expression of nuclear factor kappa B (NF-κB) p65 and toll-like receptor 4 (TLR4), and myeloperoxidase activity in lung tissues. In addition, 1,8-cineol reduced the amounts of inflammatory cells in bronchoalveolar lavage fluid (BALF), including neutrophils and macrophages, and significantly decreased the protein content in BALF and the lung wet/dry weight (W/D) ratio. Its effect on LPS-induced pulmonary inflammation was associated with suppression of TLR4 and NF-κB expressions. Our results provide evidence that 1,8-cineol inhibits acute pulmonary inflammation, indicating its potential for the treatment of acute lung injury.

Astragalus Polysaccharide Protects Astrocytes from Being Infected by HSV-1 through TLR3/NF-κB Signaling Pathway.

Astragalus polysaccharide (APS) is the most immunoreactive substance in Astragalus. APS can regulate the body's immunity and is widely used in many immune related diseases. However, till now, there is little information about its contribution to the protection of astrocytes infected by virus. Toll-like receptor 3 (TLR3) is a key component of the innate immune system and has the ability to detect virus infection and trigger host defence responses. This study was undertaken to elucidate the protective effect of APS on herpes simplex virus (HSV-1) infected astrocytes and the underlying mechanisms. The results showed that APS protected the astrocytes from HSV-1 induced proliferation inhibition along with increasing expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) markedly. Moreover, APS significantly promoted the expression of Toll-like receptor 3 (TLR3) and the activation of nuclear factor-κB (NF-κB) in astrocytes. In addition, while astrocytes were pretreated with TLR3 antibody before adding HSV-1 and APS, the expression of TLR3, TNF-α, and IL-6 and the activation of NF-κB decreased sharply. These results indicate that APS can protect astrocytes by promoting immunological function provoked by HSV-1 through TLR3/NF-κB pathway.