Research progress on role of traditional Chinese medicine in hepatic fibrosis based on miRNA-mediated activation of NLRP3 inflammasome / 中国中药杂志

In recent years, liver fibrosis has become a hotspot in the field of liver diseases. MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3) inflammasome activation is pivotal in the pathogenesis of liver fibrosis. The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis. Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation, including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway, miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway, miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1), miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factor κB(NF-κB) inflammatory pathway, miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-α inducible protein 3(A20), and miR-20 b-promoted expression of IL-1β and IL-18 by activating NLRP3 signaling pathway. Additionally, the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma, Glycyrrhizae Radix et Rhizoma, Aurantii Fructus, Polygoni Cuspidati Rhizoma et Radix, Moutan Cortex, Paeoniae Radix Alba, Epimedii Folium, and Cinnamomi Cortex) was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.

Clinical application of stress/rest myocardial perfusion imaging in the patients with 50 ％-75 ％ coronary stenosis / 中华核医学杂志

Objective To evaluate the clinical application of stress/rest MPI in the patients with 50％-75％ coronary artery stenosis.Methods The criteria for patient selection were that the patients should have at least one main coronary artery with stenosis more than 50％,and the maximal stenosis should be less than 75％ according to CAG.The stress/rest MPI was performed in 2 weeks before or after CAG.A total of 244 patients (178 males,66 females) with mean age (57 ± 10) years were included in this study.Symptom restriction stress test was used and stress MPI was performed 1 - 1.5 h after 99Tcm-MIBI (925 MBq)injection at the exercise peak.Rest MPI was performed within 48 - 72 h after stress MPI.Myocardial ischemia was diagnosed when there was a reduced uptake or even a defect in 2 different tomographic sections or in the same part of a myocardium in the continuous 2 slices.When there was an irreversible reduced uptake or defect,myocardial infarction was given as the final diagnosis.No reduced uptake or defect in all slices was shown as normal.The impact of MPI images on the selection for optimal clinical therapy plans was also discussed.X2 test was used for statistical analysis.Results A total of 340 coronary arteries with stenosis 50％ - 75％ were found by CAG.According to stress/rest MPI results,207 patients (84.8％)presented normal,33 had myocardial ischemia,3 had myocardial infarction,and 1 had both myocardial infarction and ischemia.In abnormal MPI images,there were 61 ischemic segments and 9 infarct segments,which were associated with 43 stenotic arteries (23 LAD,10 LCX,and 10 RCA).Patients were divided into 2 groups according to the results of MPI:Group 1 with normal MPI (207/244,84.8％ ) and Group 2 with abnormal MPI (37/244,15.2％ ).In Group 1,9 patients underwent coronary artery revascularization (PTCA or CABG),and the others had medical treatment.Eight patients had PTCA and 29 patients had medical treatment in Group 2.There was a statistically significant difference between the two groups ( X 2 =11.9,P =0.001 ).Conclusion Stress-rest MPI may be an effective method to evaluate ischemia degree for patients with 50％ -75％ coronary artery stenosis and a useful indicator for the individual treatment.

18F-FDG/99Tcm-MIBI SPECT myocardial imaging for the detection of myocardial viability in patients with acute myocardial infarction / 中华核医学杂志

Objective To investigate the value of 18F-FDG/99Tcm-MIBI SPECT myocardial imaging for the detection of myocardial viability and prognosis in patients with AMI. Methods 18F-FDG/99Tcm-MIBI SPECT myocardial imaging was performed in 98 consecutive patients [man 87, women 11; average age (58 ±11)y] with AMI. The myocardium was scored individually for nine segments: mildly decreased uptake = 1,significantly decreased uptake = 2, and no uptake = 3. Perfusion defect but preserved 18 F-FDG uptake was defined as perfusion-metabolism mismatch, indicating jeopardized but viable myocardium. Perfusion defect and decreased 18 F-FDG uptake were defined as match, indicating myocardial necrosis. Echocardiogram was performed before and after treatment for evaluating the LVEF. All patients were followed after treatment.The rate of cardiac events was calculated and compared between patients with medication and revascularization. Paired t test, Chi-square test and log-rank test were used for statistical analysis. Results In the group with viable myocardium, 27 patients received revascularization and 10 received medication. In the group with infarcted myocardium, 26 patients received medication and 35 received revascularization. Patients underwent revascularization and with medication had no significant difference in improvement of LVEF between both groups (viable myocardium group: χ2 = 0.509, P > 0. 05; infarcted myocardium group: χ2 =0.035, P > 0.05). In viable myocardium group, cardiac event rate was significantly higher in patients with medication than in those who had undergone revascularization (50.0% vs 14.8%, χ2 =4.91, P<0.05).In the infarcted myocardium group, cardiac event rate was also significantly higher in patients with medication (30.7% vs5.7% ,χ2 =6.83, P<0.05). Conclusions 18F-FDG/ -MIBI SPECT myocardial imaging may well be of value but limited for the detection of myocardial viability and prediction of improvement in cardiac function as well as prognosis. However, more prospective data are needed for final evaluation.

Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in human and nude mouse ectopic endometrium and the effect of estrogen and progestin on their expression / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the roles of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinase-1(TIMP-1) in the pathogenesis of endometriosis and the effects of estrogen and progestin on their expression.</p><p><b>METHODS</b>Immunohistochemistry and RT-PCR were employed to detect the expression of MMP-1 and TIMP-1 in the ectopic tissues of 35 patients with endometriosis, 22 eutopic endometrium tissues from women with endometriosis and 28 normal controls. Fifty-nine nude mice were injected with human late secretory endometrial chippings and randomized into estrogen group, progestin group, estrogen-progestin group and control group with corresponding treatments. The implantation rates and graft morphology were observed and MMP-1 and TIMP-1 expressions in the grafts detected by immunohistochemistry.</p><p><b>RESULTS</b>Typical endometrial glands and stroma were observed in all the groups with comparable implantation rates. The administration of progestin was associated with multiple peritoneal implantation sites and significantly larger implants. The transplanted endometria showed proliferative or secretory changes with estrogen or progestin administration. MMP-1 expression significantly increased and TIMP-1 expression decreased with increased MMP-1/TIMP-1 ratio in human and nude mouse ectopic endometria in comparison with those in normal endometria (P<0.05, P<0.01). MMP-1 expression was higher in estrogen and estrogen-progestin groups than in the control group, and was lower in the 3 sexual hormone-treated groups than in the control group. MMP-1 mRNA expression in the eutopic endometrium was significantly higher than that in the normal endometria.</p><p><b>CONCLUSION</b>Progestrin can not inhibit MMP-1 expression or the effect of estrogen on ectopic endometrium known as progestin resistance. The high expression of MMP-1 and low expression of TIMP-1 in endometriotic tissues confer strong invasiveness of ectopic endometrial tissue, especially in eutopic endometrial tissue, and may play an important role in the pathogenesis of endometriosis.</p>

Intrathecal injection of MK-801 inhibited the NOS activity and NO content of hippocampus in rat during the process of formalin-induced inflammatory pain / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of intrathecal injection of MK-801, a NMDA receptor antagonist, on the NOS activity and NO content of hippocampus in rat during the process of formalin-induced inflammatory pain as well as the pain behavior of rat.</p><p><b>METHODS</b>The degree of pain was determined by observing the time of licking and biting the injected paw. NOS expression in the hippocampus was determined by using NADPH-d histochemical staining. NO content of hippocampus was determined by assaying NO3; and NO2.</p><p><b>RESULTS</b>Subcutaneous injection of formalin elicited a characteristic pain behavioural response consisting of licking and biting the injected paw, etc. Intrathecal injection of MK-801 could shorten obviously the time of licking and biting representing pain behavioural response in phase 2. It is suggested that intrathecal injection of MK-801 could block the pain behavioural response induced by formalin (P < 0.05). The number and staining degree of NADPH-d positive neurons in formalin group significantly increased at 12 h after the formalin injection in CA1, CA2-3 and DG of hippocampus compared with control group as well as NO content, however, the number and staining degree of NADPH-d positive neurons in formalin + MK-801 group significantly decreased in contrast to those of formalin 12 h group as well as the NO content (P < 0.01).</p><p><b>CONCLUSION</b>Intrathecal injection of NMDA receptor antagonist MK-801 could inhibit the NOS activity and NO production in hippocampus of rat, which showed the increase of hippocampal NO production was mainly induced by the peripheral nociceptive information input.</p>

Formalin-induced pain enhanced nitric oxide synthase expression and nitric oxide production in the rat hippocampus / 中国应用生理学杂志

<p><b>AIM</b>To observe the changes of nitric oxide synthase (NOS) activity and nitric oxide (NO) content of hippocampus including their time course and region distribution character in rat during the process of formalin-induced inflammatory pain as well as the pain behavior of rat.</p><p><b>METHODS</b>The pain threshold (PT) was determined by radiant heat-induced tail flick test. NOS expression in the hippocampus was determined by using NADPH-d histochemical staining. NO production in hippocampus was determined by assaying NO3- and NO2-.</p><p><b>RESULTS</b>Subcutaneous injection of formalin elicited nociceptive behavioural response and led to decrease in PT of rat. The number and staining degree of NADPH-d positive neurons began to increase at 6 h after the formalin injection in CA1, CA2 - 3 and DG of hippocampus as well as NO content, which increased most obviously at 12 h and returned to control level at 48 h.</p><p><b>CONCLUSION</b>Formalin-induced inflammatory pain could induce the elevation of NOS activity in CA1, CA2 - 3 and DG of hippocampus with a certain time course, which further led to a increase of NO production in hippocampus.</p>

Effects of scopolamine on morphine-dependence in mice and the relationship between the effect and hippocampus intracellular calcium / 中国应用生理学杂志

<p><b>AIM</b>To observe the effect and mechanism of scopolamine on morphine(Mor)-induced mice dependence.</p><p><b>METHODS</b>The Mor-dependent mice model was established by intraperitoneal (ip) administered Mor for seven days. Pain threshold, times of jump and hippocampus intracellular free calcium ion concentration ([Ca2+]i) were determined by the heat plate test, naloxone (Nal)-precipitated jumping response and flow cytometry, respectively.</p><p><b>RESULTS</b>The pain threshold of Mor-dependent mice decreased significantly while there was a marked increase in times of jump, the rate of jumping animals and hippocampus [Ca2+]i. Co-administered scopolamine, the pain threshold of Mor-dependent mice increased significantly; the number of jump, the rate of jumping animals and hippocampus [Ca2+]i all decreased significantly.</p><p><b>CONCLUSION</b>Scopolamine could antagonize the Mor-induced mice dependence, which could be related to decreasing the levels of brain intracellular free calcium.</p>

Protein kinase C agonist phorbol 12-Myristate-Acetate induces nociception and enhances nitric oxide production in the spinal cord of rats / 中国应用生理学杂志

<p><b>AIM</b>To determine the involvement of NO signal pathway in the development of hyperalgesia induced by activation of protein kinase C (PKC ), nociceptive responses and nitric oxide synthase(NOS) expression and nitric oxide (NO) content in the spinal cord were observed after administration of Phorbol 12-Myristate-Acetate (PMA), a PKC agonist, in rats.</p><p><b>METHODS</b>Nociceptive response was observed by behavioral approach. Pain threshold was assayed using thermal tail-flick test. NADPH-d histochemistry was used to investigate the changes of NOS expression. Nitrate/nitrite (NO3-/NO2-) was assayed to represent NO content of lumbar enlargement of spinal cord.</p><p><b>RESULTS</b>Nociceptive response was induced and pain threshold decreased after intrathecal injection of PMA. The number of NADPH-d positive cells increased significantly in the superficial layer of the spinal cord dorsal horn (Laminae I - II ) and the grey matter surrounding the central canal (Laminae X), and the reactive degree of NADPH-d positive soma and processes and NO content of the lumbar enlargement of the spinal cord increased significantly after intrathecal injection of PMA. Pretreatment of PKC inhibitor chelerythrine chloride blocked the changes induced by PMA.</p><p><b>CONCLUSION</b>The activation of PKC in the spinal cord neurons might induce spontaneous nociceptive responses and hyperalgesia in rats, as well as promote NOS expression and NO production, suggesting that increase in NO production is one of mechanisms of hyperalgesia induced by activation of PKC.</p>