Circulating immune cell phenotyping is potentially relevant for diabetic retinopathy risk assessment.

BACKGROUND: Inflammation is believed to play a central role in the development of diabetes mellitus and is a common feature of type 2 diabetes mellitus (T2DM). However, the association with diabetic retinopathy (DR) remains a topic of debate. METHODS: This study employed two-sample bidirectional Mendelian randomization (MR) analyses to establish causal associations between immune cell characteristics and DR. Using publicly available GWAS genetic data, we investigated the causal relationship between 731 immune cell characteristics and the risk of DR. A total of four types of immune features, including relative cell (RC), absolute cell (AC), median fluorescence intensities (MFI), and morphological parameters (MP), were included. Sensitivity analysis was conducted to assess the robustness, heterogeneity, and potential horizontal pleiotropy of the results. RESULTS: Thirty-five immune cell phenotypes were correlated with the risk of developing DR among four immune traits (MFI, RC, AC, and MP), and DR resulted in altered expression of twenty-six immune cells. CONCLUSION: We have demonstrated a strong correlation between immune cell traits and DR using a genetic approach. This finding offers valuable insights for early DR prevention and future clinical research and treatment.

Xianling Lianxia formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is characterized by high invasiveness. Trastuzumab considerably improves the prognoses of HER2-positive BC, but some patients exhibit drug resistance. In this study, the effects of XLLXF combined with trastuzumab on the proliferation, apoptosis, invasion, and migration of HER2-positive BC cells are evaluated, and network pharmacology is performed. Then, we conduct an in vivo study using a xenograft mouse model of HER2-positive BC, and tumor growth is monitored. The expression levels of cytokines are measured by ELISA. Molecular docking is performed to observe the binding stability of IL2, JAK, STAT, and TNF with curcumenol, icariside-II, lobetyolin, and scutellarein. Finally, we observe changes in JAK1 and TNF-α in tumor tissues by immunohistochemistry. The results show that XLLXF enhances the inhibitory effects of trastuzumab on the proliferation, colony formation ability, migration, and invasion of HER2-positive BC cells and promotes apoptosis. Network pharmacology reveals that XLLXF may exert its effects on HER2-positive BC by modulating pathways such as the ErbB, JAK-STAT, and NF-κB pathways. Potential targets include cytokines closely related to immune function. In the in vivo study, XLLXF synergistically enhances the inhibitory effects of trastuzumab on tumor growth. ELISA reveals that XLLXF combined with trastuzumab increases the levels of IL-15, IL-2, TNF-α, and IFN-γ in tumor-bearing mice. Immunohistochemistry confirms that XLLXF can regulate the expressions of JAK1 and TNF-α. This study demonstrates that XLLXF can synergistically enhance the efficacy of trastuzumab in targeting HER2-positive BC. The mechanism may involve the modulation of inflammatory factors.

Sepsis Impairs Purkinje Cell Functions and Motor Behaviors Through Microglia Activation.

The most common clinical manifestation of sepsis-related encephalopathy (SAE) is the deterioration of cognitive function. Besides, increasing evidence shows that SAE patients exhibit coordination and sensorimotor dysfunctions, suggesting that SAE affects motor function with unclear mechanism. In the present work, we explored the effects of SAE on cerebellar Purkinje cells (PCs) using cecal ligation and perforation (CLP), a standard model for inducing sepsis symptoms similar to those in human patients. Our results show that the sepsis can activate microglia in the cerebellum and promote the secretion of inflammatory factor TNF-α, which increases intrinsic excitability and synaptic transmission of PCs, inhibits the synaptic plasticity of PCs, and impairs motor learning of mice. These findings address how SAE changes PC functions, and thereby are of great significance to reveal pathophysiological feathers of human patients suffering from SAE.

Dual Functional Ultrasensitive Point-of-Care Clinical Diagnosis Using Metal-Organic Frameworks-Based Immunobeads.

Sepsis is an acute systemic infectious syndrome with high fatality. Fast and accurate diagnosis, monitoring, and medication of sepsis are essential. We exploited the fluorescent metal-AIEgen frameworks (MAFs) and demonstrated the dual functions of protein detection and bacteria identification: (i) ultrasensitive point-of-care (POC) detection of sepsis biomarkers (100 times enhanced sensitivity); (ii) rapid POC identification of Gram-negative/positive bacteria (selective aggregation within 20 min). Fluorescent lateral flow immunoassays (LFAs) are convenient and inexpensive for POC tests. MAFs possess a large surface area, excellent photostability, high quantum yield (∼80%), and multiple active sites serving as protein binding domains for ultrasensitive detection of sepsis biomarkers (IL-6/PCT) on LFAs. The limit of detection (LOD) for IL-6/PCT is 0.252/0.333 pg/mL. Rapid appraisal of infectious bacteria is vital to guide the use of medicines. The dual-functional fluorescent MAFs have great potential in POC tests for the clinical diagnosis of bacterial infections.

Activation of aryl hydrocarbon receptor by azatyrosine-phenylbutyric hydroxamide inhibits progression of diabetic retinopathy mice.

Diabetic retinopathy (DR) is a severe consequence of long-term diabetes mellitus and may lead to vision loss. Retinal pigment epithelial (RPE) cells are a diverse group of retinal cells with varied metabolic and functional roles. In hypoxic conditions, RPE cells have been shown to produce angiogenic factors, such as vascular endothelial growth factor (VEGF), which is regulated by hypoxia-inducible factor 1-alpha (HIF1A). VEGF plays a crucial role in angiogenesis in DR. In the present study, we investigated whether azatyrosine-phenylbutyric hydroxamide (AZP) has therapeutic effect on DR therapy. In this study, we treated high glucose-activated human retinal pigment epithelial cells (ARPE-19) with and without AZP. The effector proteins were evaluated using western blotting. In the in vivo study, AZP was administered to the db/db mice as a DR animal model. Moreover, invasive imaging techniques such as optical coherence tomography (OCT), fundus photography, and fundus fluorescein angiography (FFA) were performed on the mice to assess DR progression. We found that treatment of AZP for 12 weeks reversed increasing DR retinal alterations in db/db mice, decreasing vascular density, retinal blood perfusion, retinal thickness, decreasing DR lesion, lipofuscin accumulation, HIF1A, VEGF, and inflammation factor expression. In addition, AZP treatment could activate the aryl hydrocarbon receptor AHR and reverse the high-glucose-induced HIF1A and VEGF in ARPE-19 cells and db/db mice. In conclusion, AZP activated AHR while inhibiting HIF1A and VEGF. This study indicates that AZP may be a promising therapeutic agent for treating DR.

Effects of Bacillus subtilis on Production Performance, Bone Physiological Property, and Hematology Indexes in Laying Hens.

This study was to investigate the effects of Bacillus subtilis on production performance and bone pathophysiological characteristics of layers. Twenty-four 48-week-old Lohmann Pink-shell laying hens were randomly divided into two groups: a basic diet (control) and the basic diet mixed with Bacillus subtilis (0.5 g/kg) for a 60-day trial. Statistically, independent-sample t-test was used to assess the treatment differences. The results showed that Bacillus subtilis supplementation improved the percent of marketable eggs (p < 0.05) with reduced numbers of broken and soft-shelled eggs but had no effects on egg weight, height of albumen, yolk color, and Haugh unit (p > 0.05). Bacillus subtilis supplement also elevated maximum load (p = 0.06), maximum stress (p = 0.01), stiffness (p < 0.01), and Young's modulus (p < 0.01) but suppressed maximum strain (p = 0.06) in the femur. In addition, compared with control birds, phosphorous concentration (p < 0.01) was reduced in serum at day 61 but increased in the femur (p < 0.05) in Bacillus subtilis fed birds. Bacillus subtilis fed birds also had lower magnesium concentrations in both femur (p = 0.04) and feces (p = 0.09). Furthermore, Bacillus subtilis increased plasma estrogen concentration (p = 0.01) and femur TNF receptor superfamily member 11b (OPG) expression (p < 0.05) but reduced plasma IL-1 (p < 0.01) and TNF-α (p < 0.01) concentrations. These results indicate that Bacillus subtilis could be used as a health promotor to reduce overproduction-induced inflammation and associated bone damage and to increase marketable egg production. The data provide evidence for developing a management strategy to use Bacillus subtilis as a feed additive to improve marketable egg production and health and welfare status of laying hens.

Efficacy of faecal microbiota transplantation on ulcerative colitis and its effect on gastrointestinal motility and immune function.

OBJECTIVE: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of ulcerative colitis (UC) and its effect on gastrointestinal motility (GM) and immune function. METHODS: A retrospective cohort study was conducted on 47 UC patients. The patients were divided into an observation group (n=17, treated with FMT) and a control group (n=30, treated with conventional treatment) according to the treatment regimen. In the observation group, FMT was used to treat colonic lesions by transplanting colonic bacteria fluid from healthy people. Clinical efficacy, immune function, level of inflammatory factors and gastrointestinal function of the two groups were observed before and after treatment. RESULTS: The total response rates of observation group was 94.12%, which was higher than that of control group (70.00%; P<0.05). After treatment, the contents of CD3+, CD4+ T cells and CD4+/CD8+ ratio were increased, while the content of CD8+ T cells was decreased in both groups compared with those before treatment (all P<0.05); and the contents of CD3+, CD4+ T cells and CD4+/CD8+ ratio in the observation group were higher than those in the control group, while CD8+ T cells showed an opposite trend (P<0.05). The levels of immunoglobulin A, immunoglobulin G and immunoglobulin M as well as interleukin-6, C-reactive protein, tumor necrosis factor-α and motilin were lower than those before treatment in both groups (all P<0.05), and the decreases in the observation group were more significant than those in the control group (all P<0.001). After treatment, cholecystokinin and vasoactive peptide were higher than those before treatment in both groups (all P<0.05), and the increased degree in the observation group was more obvious than that in the control group (all P<0.001). CONCLUSION: FMT has significant clinical efficacy in the treatment of UC, which may be related to the improvement of immune function, alleviation of inflammatory response and promotion of GM recovery.

Establishment and Validation of Nomogram Model Integrated With Inflammation-Based Factors for the Prognosis of Advanced Non-Small Cell Lung Cancer.

OBJECTS: Inflammation is one of the hallmarks of cancer. Tumor-associated inflammatory response plays a crucial role in enhancing tumorigenesis. This study aimed to establish an effective predictive nomogram based on inflammation factors in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively evaluated 887 patients with advanced NSCLC between November 2004 and December 2015 and randomly divided them into primary (n = 520) and validation cohorts (n = 367). Cox regression analysis was used to identify prognostic factors for building the nomogram. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C-index), calibration plot, and decision curve analysis and were compared to the TNM staging system. RESULTS: The nomogram was established using independent risk factors (P < 0.05): age, TNM stage, C reaction protein-to-albumin ratio (CAR), and neutrophils (NEU). The C-index of the model for predicting OS had a superior discrimination power compared to that of the TNM staging system both in the primary [0.711 (95% CI: 0.675-0.747) vs 0.531 (95% CI: 0.488-0.574), P < 0.01] and validation cohorts [0.703, 95% CI: 0.671 -0.735 vs 0.582, 95% CI: 0.545-0.619, P < 0.01]. Decision curves also demonstrated that the nomogram had higher overall net benefits than that of the TNM staging system. Subgroup analyses revealed that the nomogram was a favorable prognostic parameter in advanced NSCLC (P < 0.05). The results were internally validated using the validation cohorts. CONCLUSIONS: The proposed nomogram with inflammatory factors resulted in an accurate prognostic prediction in patients with advanced NSCLC.

Effects of Chrysophanol on the Activation of Microglia and the Expression of Inflammatory Factors in Cerebral Ischemia Model Rats / 中国药房

OBJECTIVE：To study the effects of chrysophanol on the activa tion of microglia and the expression of inflammatory factors in cerebral ischemia model rats. METHODS ：SD rats were randomly divided into sham operation group ， model group and chrysophanol high ，medium，low dose groups [7.88，3.94，1.97 mg/（kg·d）]，with 20 rats in each group （the number was complemented in cases of death or unsuccessful modeling during modeling process ）. Except for sham operation group ， middle cerebral artery occlusion model was established in other groups by improved thread method. After 2 hours of ischemia ， sham operation group and model group were intraperitoneally injected with 1 mL normal saline ，and each administration group was intraperitoneally injected with 1 mL corresponding drug ，once a day ，for 7 consecutive days. After last medication ，the score of neurological impairment was recorded ；cerebral infarction of rats was observed by TTC staining ，and the percentage of cerebral infarction area was calculated. The expression of Iba- 1 positive cells in ischemic penumbra of rats was observed by immunofluorescence staining. The expression of Notch- 1，TNF-α and ICAM-1 in the ischemic penumbra of rats were detected by Western blotting assay. RESULTS ：In sham operation group ，there was no infarction area in the brain tissue ，and the Iba- 1 positive cells in the ischemic penumbra were few and branched. Compared with sham operation group ，the infarction area of cerebral tissue in rats was obvious in model group ； the 052）number of Iba- 1 positive cells in ischemic penumbra were 〔ZQ2017003〕） increased significantly ，and they were in amoeba or round shape；the neurological impairment score ，the percentage of cerebral infarction area ， relative expression of Notch- 1， TNF-α and ICAM-1 protein in ischemic penumbra were increased significantly （P＜0.05）. Compared with m odel rats ，the infarction area of cerebral tissue in each dose group of chrysophanol was reduced to different extent ；the number of Iba- 1 positive cells in ischemic penumbra was decreased ；neurological impairment score ，the percentage of cerebral infarction area ，relative expression of Notch- 1，TNF-α and ICAM-1 protein were significantly decreased （P＜0.05 or P＜0.01）. CONCLUSIONS ：Chrysophanol has a certain protective effect on the brain tissue of cerebral ischemia model rats ，and can relieve the nerve injury. Its mechanism may be associated with inhibiting the activation of microglia and expression of inflammatory factors mediated by Notch pathway.

Xian-Ling-Gu-Bao induced inflammatory stress rat liver injury: Inflammatory and oxidative stress playing important roles.

ETHNOPHARMACOLOGICAL RELEVANCE: Xian-Ling-Gu-Bao (XLGB) Fufang is an herbal formula that has been used in clinical settings to treat osteoporosis, osteoarthritis, aseptic bone necrosis, and climacteric syndrome. Despite its uses, XLGB treatment has been linked to potential liver injury. To date, there is a lack of clear demonstration of such toxicity in animal models. AIM OF THE STUDY: As animal models fail to reproduce the XLGB hepatotoxicity reported in humans, because human hepatocytes are clearly more sensitive to XLGB, this study was designed to investigate a more reliable animal model of such toxicity. MATERIALS AND METHODS: We randomized rats into five groups, as follows: CON (control), XLGB, lipopolysaccharide (LPS), L-XLGB/LPS (XLGB, 0.125 g/kg; LPS, 0.1 mg/kg), and XLGB/LPS (XLGB, 1.25 g/kg; LPS, 0.1 mg/kg). These groups were treated with 0.5% sodium carboxymethyl cellulose (CMC-Na), XLGB suspension, normal saline, or LPS. The first administration of XLGB [0.125 g/kg or 1.25 g/kg, by mouth (PO)] or its solvent (0.5% CMC-Na) was delivered, and then food was removed. Twelve hours after the first administration of XLGB, rats received LPS [0.1 mg/kg, intravenously (IV)] or saline control. After 30 min, a second administration of XLGB (0.125 g/kg or 1.25 g/kg, PO) or solvent was administered. The rats were anesthetized at 12 h or 24 h following the second administration of XLGB. Liver function was evaluated by measuring liver weight, liver microscopy, serum biochemistry and plasma microRNA-122 (miR-122). The plasma levels of 27 cytokines were measured to evaluate inflammation. Moreover, the expression of cytochrome P450 2E1 (CYP2E1), nicotinic adenine dinucleotide phosphate (NADPH) oxidase and inducible nitric oxide synthase (iNOS) at protein levels were observed; immunofluorescence and immunohistochemistry were used to confirmed the hepatotoxicity of XLGB. RESULTS: Hepatotoxicity in male rats with moderate inflammation induced by XLGB was indicated by liver histopathology, serum biochemical analysis, serum miR-122 levels, and immunofluorescent assessments. We observed significant increases in liver weight and liver indexes in male rats with moderate inflammation in response to XLGB. Histopathological assessment further showed that extensive hepatocellular necrosis and inflammatory infiltration were evident in rats co-treated with XLGB/LPS. The levels of serum transaminases [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT)], total bilirubin (TBIL) and triglyceride (TG), which are markers of liver function, were also significantly increased by XLGB/LPS treatment. Similarly, miR-122 was significantly elevated in XLGB/LPS treated rats relative to other groups. An immunofluorescent assessment showed extensive apoptosis in hepatocytes from these co-treated rats. What is more, XLGB can dose-dependently induce liver injury in male rats with moderate inflammation. Hepatic CYP2E1, neutrophil chemotactic factor (NCF-1), iNOS, and NOX-2 (an NADPH oxidase subunit) levels were increased in response to XLGB treatment, and staining for DMPO nitrone adducts further showed elevated oxidative stress level in XLGB/LPS-treated rats relative to the other experimental groups. CONCLUSION: LPS and XLGB co-treatment in rats led to marked hepatotoxicity. This toxicity was associated with disrupted lipid metabolism, extensive liver necrosis and inflammatory infiltration, apoptosis, and expression of oxidative stress-related proteins. These results demonstrate a valuable model for the study of iDILI in the context of XLGB treatment, and further provide insights into the potential mechanisms by which XLGB may induce hepatotoxicity in humans.

Effects of Nicorandil on Vascular Endothelial Function and Angina Pectoris Recurrence in Patients with Unstable Angina Pe- ctoris after Percutaneous Coronary Intervention / 中国药房

OBJECTIVE： To observe the effects of nicorandil on vascular endothelial function and angina pectoris recurrence in patients with unstable angina pectoris after percutaneous coronary intervention （PCI）. METHODS： Totally 195 patients with unstable angina pectoris were collected from Sichuan Provincial People’s Hospital during Jan. 2016-Mar. 2018， and then divided into control group （97 cases） and observation group （98 cases） according to random number table. Both groups received PCI， and then given basic treatment as Enoxaparin sodium injection， Isosorbide mononitrate sustained-release tablets， Aspirin enteric-coated tablets， Clopidogrel sulfate tablets and Atorvastatin calcium tablets after PCI. Observation group additional received Nicorandil tablet 5 mg， tid， on the basis of control group. Both groups were treated for 6 months. The levels of vascular endothelial function related indexes （FMD， ET-1， NO）， myocardial injury markers （cTnⅠ， CK-MB） and inflammatory factors （hs-CRP） were observed before and after PCI. The recurrent angina pectoris， the occurrence of MACE and ADR were recorded. RESULTS： 6 patients of control group and 4 patients of observation group withdrew from the study. One day before operation， there was no significant difference in the levels of vascular endothelial function， myocardial injury markers or inflammatory factors between 2 groups （P＞0.05）. One day after operation， the levels of FMD and NO in both groups decreased significantly， while the levels of ET-1， cTnⅠ and CK-MB increased significantly （P＜0.05）. The levels of FMD and NO were increased significantly in the 1st and 6th months after surgery， and the observation group was significantly higher than the control group； the levels of ET-1， cTnⅠ， CK-MB and hs-CRP were decreased significantly， and the observation group was significantly lower than the control group （P＜0.05）. The incidence and times of recurrent angina pectoris， duration， the proportion of grade Ⅲ angina pectoris and total incidence of MACE in observation group were significantly lower， less or shorter than control group （P＜0.05）. There was no statistical significance in total incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS： Additional use of nicorandil can improve vascular endothelial function， relieve the myocardial injury and inflammatory response， reduce the occurrence of recurrent angina pectoris and MACE after PCI and doesn’t influence the safety of routine treatment.

Mechanical stretch aggravates aortic dissection by regulating MAPK pathway and the expression of MMP-9 and inflammation factors.

This study aimed to explore whether mechanical stretch aggravated aortic dissection through regulating MAPK pathway, MMP-9, and inflammation factors. We first established aortic dissection model rats. Mechanical stretch (3 g) was exerted on vascular ring of aortic dissection which was also treated by inhibitors of MAPK pathway (SB203580, SP600125, and U0126). HE and Masson staining showed that aortic dissection severity with 3 g tension was worse than that without tension (0 g); after the treatments of diverse inhibitors, the fracture and breakage of the elastic fibers decreased. The expression of MMP-9, TNF-α, IL-1ß) p38/p-p38, JNK1/p-JNK1, and ERK1/2/p-ERK1/2 were determined by immunohistochemical analysis, RT-PCR, and western blot. No matter whether tension was exerted or inhibitors were added, there was no change in the expression of p38, JNK1, and ERK1/2. However, compared to the 0 g group, the expression of MMP-9, TNF-α, IL-1ß, p-p38, p-JNK1, and p-ERK1/2 was significantly upregulated in the 3 g group (P < 0.05). In both 0 g and 3 g groups, the expression of MMP-9, TNF-α, IL-1ß, p-p38, p-JNK1, and p-ERK1/2 was remarkably downregulated after inhibitors treatment (P < 0.05). In conclusion, mechanical stretch aggravated aortic dissection by regulating the MAPK pathway and the consequent expression of MMP-9 and inflammation factors.

Intracerebroventricular injection of miR-146a relieves seizures in an immature rat model of lithium-pilocarpine induced status epilepticus.

OBJECTIVE: Status epilepticus (SE) is a common, life-threatening neurological emergency that confers a high degree of morbidity and mortality. Increasing evidence indicates that neuroinflammation plays a critical role in the pathogenesis of SE. MicroRNA-146a (miR-146a) has been reported to be an important posttranscriptional inflammation-associated microRNA. The aim of this study was to investigate the effect of miR-146a in SE and the mechanism by which it operates. METHODS: To study the effect of miR-146a in SE, we chose intracerebroventricular injection for rat at 21-28days old, and made a lithium-pilocarpine-induced SE rat model. We assessed latency time and Lado grade by behavior observation. We performed qPCR, ELISA and western blot tests on rat hippocampus to measure the expression levels of miR-146a, IL-1ß, TNF-α, TLR4 and NF-κB. RESULTS: In the miR-146a antagomir injection group, the latency to generalized convulsions was shorter, the duration and degree of seizures were more severe, the expression level of miR-146a was clearly decreased, and IL-1ß, TNF-α, TLR4 and NF-κB were all significantly up-regulated. The opposite was true for rats treated with miR-146a agomir. CONCLUSION: Our findings elucidate the role of inflammation in the pathogenesis of SE in immature rats, and show that regulating the expression level of miR-146a may provide a novel insights into the pathogenesis of SE.

Drunkenness increases the expressions of inflammatory factors and brain edema after traumatic brain injury in rats / 医学研究生学报

Objective The expressions of inflammatory factors and brain edema after traumatic brain injury (TBI) are the main factors for deterioration of the condition.TBI after drunkenness is even more difficult to be managed than simple TBI.This study was to discuss the effects of drunkenness on the inflammatory factors TNF-o and IL-6 and the aquaporin-4 (AQP-4) protein in rats after TBI.Methods Forty-eight male adult SD rats were randomly divided into a TBI and an ethanol (ETH) pretreatment group.TBI was induced using the Feeney's method after intraperitoneal injection of 3％ chloral hydrate at 30 mg/kg (the TBI group) or following gavage of ETH (the ETH group).At 1,3 and 5 days after modeling,modified neurological function scores (mNSS) were obtained,the expressions of TNF-α,IL-6 and AQP-4 protein determined by Western blot,and the levels of TNF-α.IL-6 and AOP-4 mRNA measured by RT-PCR at 6,24 and 72 hours.Results Compared with the TBI group,the ETH group showed significantly decreased mNSS at 1 day (9.00±0.63 vs 7.17±1.72,P＜0.05),3 days (7.00±1.10 vs 4.83±1.47,P＜0.05) and 5 days after modeling (5.50±1.05 vs 3.83± 0.75,P＜ 0.05),but remarkably up-regulated expressions of TNF-α (0.068± 0.008 vs 0.257 ± 0.008,P＜ 0.01),IL-6 (0.102 ±0.013 vs 0.320±0.016,P＜0.01) and APQ4 (0.054±0.007 vs 0.212±0.015,P＜0.01) at 6 hours,as well as at 24 and 72 hours (P＜0.01).Conclusion Drunkenness may increase the expressions of inflammatory factors and brain edema after traumatic brain injury and consequently aggravate secondary brain injury.

Elderly-customized hatha yoga effects on the vascular inflammation factors of elderly women.

[Purpose] The aim of this study was to examine the effects of the application of elderly-customized hatha yoga on the vascular inflammation factors of elderly women. [Subjects and Methods] This research was conducted with 14 elderly women, between 70 and 80 years old, divided into an elderly-customized hatha yoga group (n=7) and a control group (n=7). The application group participated in a hatha yoga program designed to be elderly-friendly for 10 weeks. At the end of the program, the vascular inflammation factors were measured, including the albumin, white blood cell count, fibrinogen, high sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR). [Results] In the hatha yoga group, the albumin increased significantly after the application, when compared to the level before the application, while the fibrinogen, hs-CRP, and ESR decreased significantly. In the control group, the vascular inflammation factor levels before and after the application period were not significantly different. [Conclusion] Based on the results of this study, the application of elderly-customized hatha yoga created positive changes in the vascular inflammation factors of elderly women.

Increased Mobilization of CD45+CD34+VLA-4+ Cells in Acute Viral Myocarditis Induced by Coxsackievirus B3.

OBJECTIVES: Bone marrow-derived cells (BMCs) have recently been identified to play a vital role in repairing damaged myocardium; however, it is not known whether or not mobilization of BMCs is involved in the pathogenesis of acute viral myocarditis (VMC). Thus, we analyzed the expression of CD45+CD34+VLA-4+ cells and vascular cell adhesion protein-1 (VCAM-1) in a murine model of acute VMC. METHODS: Male BALB/c mice were intraperitoneally infected with coxsackievirus B3 to establish acute VMC. The frequency of CD45+CD34+VLA-4+ cells in the heart, peripheral blood, and bone marrow was examined by flow cytometry 3, 7, 14, and 28 days after injection. Cardiac VCAM-1 and pathology scores were determined by immunohistochemistry, and myocardial VCAM-1, IL-1ß, and TNF-α were analyzed by RT-PCR and Western blot. RESULTS: In mice with acute VMC, the CD45+CD34+VLA-4+ cell population in the heart was significantly increased by day 7 and then decreased; in contrast, the CD45+CD34+VLA-4+ cell population decreased in the bone marrow and peripheral blood by day 3 and then increased. High expression of VCAM-1 was detected in the heart in parallel with CD45+CD34+VLA-4+ cell expression. CONCLUSIONS: In mice with acute VMC, VCAM-1-induced CD45+CD34+VLA-4+ cell mobilization into the injured heart is involved in the repair of injured myocardium.

Octacosanol Attenuates Inflammation in Both RAW264.7 Macrophages and a Mouse Model of Colitis.

Octacosanol has multiple biological functions. In this study, the anti-inflammatory effect and molecular mechanism of octacosanol were evaluated by using dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice and lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. The colitis mouse model was induced by 3.0% DSS in 8-week ICR mice and octacosanol orally administered with 100 mg/kg/day. The results showed that octacosanol significantly improved the health status of mice and reduced DSS-induced pathological damage in the colonic tissues. Octacosanol obviously inhibited the mRNA and protein expression levels of pro-inflammatory factors of colonic tissues. In vitro, octacosanol administration significantly reduced the expression of mRNA or protein of pro-inflammatory cytokines and the phosphorylation of c-Jun N-terminal kinase and p38, and it also partly prevented LPS-induced translocations of NF-κB and AP-1. Octacosanol has anti-inflammatory effect, and its molecular mechanism may be involved in downregulating the expression of inflammatory factors and blocking of MAPK/NF-κB/AP-1 signaling pathway.

Effect of Porphyromonas gingivalis lipopolysaccharide on gene expression of inflammatory cytokines in peritoneal macrophages of hyperlipidemic rabbits / 口腔疾病防治

Objective @#To compare the inflammatory reaction of peritoneal macrophage after Pg-LPS stimulated in healthy rabbit and hyperlipidemia rabbit. @*Methods @#12 New Zealand rabbits were randomly divided into 2 groups with 6 rabbits in each group, and normal diet and high-fat diet were fed to them respectively. The hyperlipidemia model was set up after 6 weeks. The peritoneal macrophage in normal and hyperlipidemia group were isolated and cultured, and then the cells in both groups were respectively divided into 3 groups: control, 1 μg/mL Pg-LPS, and 1 μg/mL E.coli-LPS. After 24 h treatment, the expressions of C-reaction protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6) , interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were detected by realtime PCR. @*Results @#The levels of CRP, IL-1β, IL-6, IL-8, and TNF-α were higher in hyperlipidemia control group than normal control group. The expressions of inflammatory substances were increased after stimulated by Pg-LPS, and statistically higher in hyperlipidemia rabbit group than normal group (P < 0.05). @*Conclusion@#Pg-LPS can enhance the mRNA expressions of inflammation related factors in peritoneal macrophage in hyperlipidemia rabbit.

Study on the Effects and Mechanism of Total Flavonoids from Armeniaca mume on Depression in Chronic Stress Depression Model Rats / 中国药房

OBJECTIVE:To investigate the effects and mechanism of total flavonoids from Armeniaca mume on depression in chronic stress depression model rats. METHODS:60 rats were randomly divided into normal saline group,model group,fluox-etine group(positive control,20 mg/kg)and total flavonoids from A. mume low-dose,medium-dose,high-dose groups(80,160, 240 mg/kg), 10 in each group. Except for normal saline group, the other groups adopted chronic unpredictable mild stress (CUMS)+solitary feeding condition to induce depression model. These groups were intragastrically administered,once a day,for 28 d. Changes of body mass and food intake,degree of preference for sugar were observed;forced swimming test and tail suspen-sion test were used to determine the time that rats did not move;open field test was used to determine the changes of residence time in central square,horizontal crossing lattice,standing times,modification times;tumor necrosis factor α(TNF-α),cortisol, interleukin 6 (IL-6),serotonin (5-HT) levels in serum after 24 h of last administration were determined. RESULTS:Compared with normal saline group,growth of body mass,food intake and sugar preference percentage in model group were decreased;the time that rats did not move was prolonged in forced swimming test and tail suspension test;residence time in central square was prolonged,while horizontal crossing lattice,standing times and modification times were decreased in open field test;serum levels of TNF-α,cortisol were increased,while IL-6,5-HT were decreased,with statistical significances (P<0.05 or P<0.01). Com-pared with model group,except that there were no obvious improvement in sugar preference percentage,the time that rats did not move in forced swimming test,modification times in open field test in total flavonoids from A. mume low-dose group and IL-6, 5-HT levels in serum in total flavonoids from A. mume low-dose,medium-dose groups,the above-mentioned indexes were obvious-ly improved in other groups (P<0.05 or P<0.01). CONCLUSIONS:Total flavonoids from A. mume can obviously improve the CUMS-induced depression in rats,and the mechanism may be related to inhibiting inflammation response,adjusting the hypothala-mus-pituitary-adrenal axis functions.

Inhibition of Water extract from Jiangtang Decoction on inflammation in KK-Ay mice by PI3K/Akt/NF-κB signaling pathway / 药物评价研究

Objective To study the effect and mechanism of Water extract from Jiangtang Decoction (WEJTD) on diabetes mellitus and diabetic nephropathy (DN) in spontaneous type 2 diabetes mellitus model KK-Ay mice.Methods Totally 50 KK-Ay mice were randomly divided into five groups:model group,metformin (positive drug,250 mg/kg) group,WEJTD low,medium and high dose (2,4,and 8 g/kg) group,with 10 C57BL/6J mice as normal group.The relative drugs were ig administered once a day for 12 weeks,and mice in control group and model group were perfused with distilled water of equal volume.After 12 weeks' oral administration,mice were put into metabolism cages,and the food-intake,water-intake and urine volume were calculated and collected.Blood were collected to detect the concentration of IL-6,ICAM-1 and TNF-α.Then mice were executed,and HE staining and PASM staining were used to check the effect of WEJTD on kidney.Western blotting and qRT-PCR were used to detect the concentration of PI3K,Akt,NF-κB,IL-6,ICAM-1 and TNF-α in kidney.Results WEJTD can alleviate the symptoms of diabetes,such as food ration,polydipsia and polyuria (P ＜ 0.05,0.01,and 0.001);Relief the pathological changes of kidney and significantly decreased glycogen deposition (P ＜ 0.001),down-regulate the increase of IL-6,ICAM-1 and TNF-α in serum and kidney (P ＜ 0.05,0.01 and 0.001),up-regulate the phosphorylation of PI3K and Akt (P ＜ 0.05,0.01,and 0.001),and inhibit the phosphorylation of NF-κB (P ＜ 0.001).Conclusion WEJTD had positive effects on kidney morphology of KK-Ay,and the underlying mechanism might be related to the regulation of PI3K-Akt and NF-κB-mediated inflammation.