Paeonol regulates phenotypic conversion of macrophages via estrogen receptor-a / 中国药理学通报

Aim To study the effect of paeonol on macrophage phenotvpe conversion based on estrogen receptora (ERa).Methods The macrophage Ml polarization model was established by 100 jjig • L"' LPS and 20 pug • L_1 I FN-7.ELISA was used to examine the effects of paeonol on tumor necrosis factor-a ( TNF-cx ) , interleukin-1 £ ( 1L-1 £ ) , interleukin-10 (IL-10), superoxide dismutase (SOD) , and malondi- aldehyde ( MDA).Western blot was used to detect the expression of M1 phenotvpe markers iNOS, CD86 and M2 phenotvpe markers Arg-1 and CD 163 in macrophages.Further, the methods of blockers and shRNA interference were used to verify whether the effect of paeonol was mediated by ERa.Results ELISA results shower] that paeonol reduced the content of TNF-a, IL- lp and MDA, and increased the content of IL-10 and SOD.Western blot results showed that paeonol reduced the expression of iNOS and CD86 proteins in model group, and increased the expression of Arg-1 and CD163 proteins.Both ERa selective blocker MPP and ERa shRNA reduced the efficacy of paeonol, while ERp selective blocker PHTPP had no significant effect on paeonol.Conclusion Paeonol can induce the transformation of macrophages into M2 type by ERa and alleviate the progression of atherosclerosis.

Gut microbial diversity and neurological diseases / 中国药理学通报

Gut microbiota can interact with the brain through neuronal, endocrine, immune and metabolic pathways. This interaction is called the microbiota-gut-brain axis. Increasing studies have demonstrated that the structure and diversity of gut microbes can influence host neurological diseases, including depression, Parkinson's disease and Alzheimer's disease. Abnormal gut microbial structures may cause disease, while appropri- A te microbiome prevents and cures disease. This article reviews the correlation between gut microbial diversity and some neurological diseases in order to provide new ideas and methods for the treatment of these diseases.

Pharmacological actions of miltirone in the modulation of platelet function / 中国药理学与毒理学杂志

OBJECTIVE Salvia miltiorrhiza bunge contains various active constituents, some of which have been developed as commercially available medicine. Moreover, some other ingredients in Salvia miltiorrhiza play great roles in anti-platelet activity. The aim of the present study was to investi-gate the effects and the underlying mechanism of miltirone,a lipophilic compound of Salvia miltiorrhiza Bunge. METHODS The ability of miltirone to modulate platelet function was investigated by a variety of in vitro and in vivo experiments.Platelet aggregation and dense granule secretion induced by various agonists were measured with platelet aggregometer.Clot retraction and spreading were imaged by digital camera and fl uorescence microscope. Ferric chloride-induced carotid injury model and pulmonary thromboembolism model were used to check miltirone effect in vivo. To elucidate the mechanisms of anti-platelet activity of miltirone,flow cytometry and Western blotting were performed. RESULTS Miltirone (2,4,8 μmol·L-1)was shown to suppress platelet aggregation,dense granule and α granule secretion in a dose-dependent manner. Meanwhile, miltirone inhibited the clot retraction and spreading of washed platelets.It reduced the phosphorylation of PLCγ2,PKC,Akt,GSK3β and ERK1/2 in the down-stream signal pathway of collagen receptor.It also reduced the phosphorylation of Src and FAK in the integrin αⅡbβ3 mediated"outside-in"signaling,while it did not suppress the phosphorylation of β3.In addition, miltirone prolonged the occlusion time and reduced collagen/epinephrine induced pulmonary thrombi. CONCLUSION Miltirone suppresses platelet "inside-out" and "outside-in" signaling by affecting PLCγ2/PKC/ERK1/2, PI3K/Akt and Src/FAK signaling. Therefore, miltirone might represent a potential anti-platelet candidate for the prevention of thrombotic disorders.

A study on reducing the absorption of lidocaine from the airway in cats

Abstract Purpose: To determine if the combination of lidocaine with epinephrine or gamma globulin would decrease the rate or reduce the amount of local absorption of lidocaine through the airway. Methods: Twenty adult male cats were randomly and evenly distributed into four groups: 1) Group LG: lidocaine administered with gamma globulin; 2) Group LS: lidocaine administered with physiological saline); 3) Group LE: lidocaine administered with epinephrine; 4) Group C: control group. Invasive blood pressure, heart rate, and concentration of lidocaine were recorded before and after administration. Results: The peak of plasma concentrations appeared difference (Group LG: 1.39 ± 0.23 mg/L; Group LS: 1.47 ± 0.29 mg/L and Group LE: 0.99 ± 0.08 mg/L). Compared to Group C, there were significant differences in the average heart rate of Groups LG, LS, and LE (P < 0.05). The average systolic blood pressures were significantly different when each group was compared to Group C (P < 0.05). The biological half-life, AUC0-120, peak time, and half-life of absorption among the three groups have not presented statistically significant differences (P > 0.05). Conclusion: Administering lidocaine in combination with gamma globulin through airway causes significant decrease the rate and reduce the amount of local absorption of lidocaine in cats.

Influence of tumor associated macrophages on biological function of SW620 cell / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the influence of tumor-associated macrophages (TAMs) on the biological function of SW620 cell.</p><p><b>METHODS</b>Macrophage was induced into M2-type macrophage form with interleukin (IL)-4. CD68, macrophage mannose receptor (MMR), and inducible nitric oxide synthase (iNOS) were analyzed with Western blot. SW620 was co-cultured with TAMs in the Transwell. Cytokines including IL-10, IL-12, IL-23, and tramsforming growth factor-β (TGF-β) were detected with enzyme-linked immunosorbent assay (ELISA). The activity of nuclear factor-κB (NF-κB) in SW620 was analyzed with electrophoretic mobility shift assay (EMSA). The proliferation and apoptosis of SW620 cells after co-cultured with TAM were determined with tetrazolium four nitrogen (XTT) assay and fluorescence activated cell sorting (FACS), respectively. RESULTS IL-4 induced M2 type macrophage expressed CD68 and MMR instead of iNOS. After co-cultured with SW620 for 24 hours and 48 hours, M2 type macrophage secreted higher levels of IL-10 and TGF-β than the pre-culture level (P 0.05). The activity of NF-κB in SW620 decreased by 72% and 75% after 24 hours and 48 hours compared with the pre-culture level, respectively (both P<0.01). The activity of proliferation decreased by 48% and 59% and the apoptotic rates increased by 6.37% and 7.68% and 0.37% after 24 hours and 48 hours (all P<0.01) compared with the pre-culture levels.</p><p><b>CONCLUSION</b>TAM may inhibit the proliferation and promote the apoptosis of SW620 by suppressing the activity of NF-κB.</p>

Determination of urinary polypeptide patterns of glomerulonephritis by magnetic bead separation and MALDI-TOF MS / 中华肾脏病杂志

Objective To determine the urinary polypeptide patterns of glomerulonephritis by magnetic bead separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) technology. Methods Urinary samples of 29 healthy volunteers and 34 patients with glomerulonephritis, including 10 cases of IgA nephropathy (IgAN), 10 cases of membranous nephropathy (MN), 9 cases of minimal change disease (MCD) and 5 cases of lupus nephritis (LN), were collected and separated by magnetic bead,and were screened for polypeptide patterns with a novel high throughput method, MALDI-TOF MS. Results Under the relative molecular weights 10 000 Da, 85 protein peaks were detected in healthy controls group and 109 protein peaks were detected in glomerulonephritis group. Six peaks of 3371.5 Da, 4026.35 Da, 4085.32 Da, 4116.96 Da, 4126.32 Da and 9527.31 Da were up-regulated,while 8 peaks of 861.28 Da, 1205.41 Da, 1642.52 Da, 1913.15 Da, 1976.52 Da, 2087.74 Da, 2193.47 Da and 3015.57 Da were down-regulated by more than 2 folds (P<0.01) in glomerulonephritis group as compared to healthy controls. Urinary polypeptide patterns in different diseases differed significantly from each other, indicating specific disease pattern of polypeptide excretion. Conclusions MALDI-TOF MS is a fast, convenient and high throughput analyzing method capable of screening some relative specific, potential biomarkers from the urine of glomerulonephritis patients thus it possesses better clinical value.

Possible involvement of integrin signaling pathway in the process of recovery from restraint stress in rats / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To search novel genes or pathways involved in the recovery process after restraint stress in rats.</p><p><b>METHODS</b>We compared the hypothalamus transcriptional profiles of two different recovery patterns (fast recovery vs slow recovery) from restraint stress in rats using oligonucleotide microarray, the recovery pattern was determined by the decrement of plasma adrenocorticotropic-hormone (ACTH) and corticosterone levels during one hour recovery period after stress. A real-time quantitative RT-PCR was applied to validate the differential expressed genes.</p><p><b>RESULTS</b>Analysis of the microarray data showed that most of genes were not differentially expressed between fast recovery group and slow recovery group. Among the differentially expressed genes we found that talin, together with serine/threonine protein phosphatase PP1-beta catalytic subunit (PP-1B) and integrin alpha-6 precursor (VLA-6) genes, were at least 1.5 fold up-regulated in the fast recovery group, while junctional adhesion molecule 1 (F11r) was 1.5 fold down-regulated in the fast recovery group.</p><p><b>CONCLUSION</b>The results implied that integrin signaling pathway may be involved in the recovery from restraint stress in rats. The present study provided a global overview of hypothalamus transcriptional profiles during the process of recovery from the restraint stress in rats. The integrin signaling pathway seems to be involved in the recovery process, which deserves further study to clarify the integrin-mediated recovery mechanism after restraint stress.</p>

Effects of exercise on neurogenesis in the dentate gyrus and ability of learning and memory after hippocampus lesion in adult rats / 神经科学通报·英文版

Objective To explore the effects of exercise on dentate gyrus (DG) neurogenesis and the ability of learning and memory in hippocampus-lesioned adult rats. Methods Hippocampus lesion was produced by intrahippocampal microinjection of kainic acid (KA). Bromodeoxyuridine (BrdU) was used to label dividing cells. Y maze test was used to evaluate the ability of learning and memory. Exercise was conducted in the form of forced running in a motor-driven running wheel. The speed of wheel revolution was regulated at 3 kinds of intensity: lightly running, moderately running, or heavily running. Results Hippocampus lesion could increase the number of BrdU-labeled DG cells, moderately running after lesion could further enhance the number of BrdU-labeled cells and decrease the error number (EN) in Y maze test, while neither lightly running, nor heavily running had such effects. There was a negative correlation between the number of DG BrdU-labeled cells and the EN in the Y maze test after running. Conclusion Moderate exercise could enhance the DG neurogenesis and ameliorate the ability of learning and memory in hippocampus-lesioned rats.

Forced running enhances neurogenesis in the hippocampal dentate gyrus of adult rats and improves learning ability / 生理学报

To investigate the effect of forced running in motor-driven wheel on neurogenesis in the hippocampal dentate gyrus (DG) of adult rats, 5-bromo-2-deoxyuridine (BrdU), a thymidine analog was applied to mark cell proliferation. Neuroepthelial stem cell protein (nestin) expression was used to identify neural stem/precursor cells. The BrdU- and nestin-positive cells were examined by immunohistochemical technique. The ability of learning was evaluated by Y-maze test to explore the functional role of the newborn cells in the DG after forced running. It was found that the number of BrdU- and nestin-positive cells in the DG in running groups was significantly increased compared to that in the control group (P<0.05). The effect of forced running on neurogenesis was intensity-dependent. In addition, an improvement of learning ability in Y-maze test was observed after forced running. These findings suggest that forced running in motor-driven wheel could enhance neurogenesis in the hippocampal DG of adult rats and improve learning ability.