HTNV-induced upregulation of miR-146a in HUVECs promotes viral infection by modulating pro-inflammatory cytokine release.

Increasing research has shown a link between viruses and miRNAs, such as miRNA-146a, in regulating virus infection and replication. In the current study, the association between miR-146a and hantaan virus (HTNV) infection in human umbilical vein endothelial cells (HUVECs) was investigated, with a focus on examining the expression of pro-inflammatory cytokines. The results showed that HTNV infection promoted the production of miR-146a in HUVECs and activated nuclear factor-κB (NF-κB) signaling, along with the upregulation of pro-inflammatory cytokines, including interleukin 8 (IL-8), C-C Motif Chemokine Ligand 5 (CCL5, also RANTES), interferon-inducible protein-10 (IP-10) and interferon beta (IFN-ß). Moreover, miR-146a exhibited a negative regulatory effect on the NF-κB pathway. Accordingly, a miR-146a inhibitor increased the expression of IL-8, CCL5, IP-10 and IFN-ß, whereas a miR-146a mimic reduced the levels of these cytokines. Consequently, exogenous transduction of miR-146a significantly enhanced HTNV replication in HUVEC cells. We also discovered that viral proteins (NP/GP) contributed to miR-146a expression via enhancement the activity of miR-146a promoter. In conclusion, these results imply the negative regulation of miR-146a on the production of HTNV-induced pro-inflammatory cytokines contributes to virus replication, which suggest that miR-146a may be regarded as a novel therapeutic target for HTNV infection.

[Influence of electroacupuncture stimulation of "tianshu" (ST 25), "quchi" (LI 11) and "shangjuxu" (ST 37) and their pairs on gastric motility in the rat].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of different acupoints or acupoint pairs on gastric motility so as to explore their modulation regularities under different conditions. METHODS: SD rats were randomly divided into normal control, starvation (food-deprivation for 24 h), atropine (antagonist for M-receptor), acetylcholine (Ach, agonist for M-receptor), propranolol (antagonist for beta-receptor) and clenbuterol (agonist for beta 2-receptor) and paired-acupoint groups (30 rats/group). The intragastric pressure was measured via a pressure transducer connected to a balloon inserted in the stomach cavity. EA (2 Hz /15 Hz, 2 mA) was applied to the left "Tianshu" (ST 25),"Quchi" (LI 11) and "Shangjuxu" (ST 37) which were formed in pairs: ST 25-LI 11, ST 25-ST 37 and LI 11-ST 37 for 2 min following intravenous injection of atropine (0.1%, 0.8 mL/kg, 40 microL x min(-1) x kg(-1)), 0.1% acetylcholine (20 microL x min(-1) x kg(-1)), 0. 2% clenbuterol (80 microL x min(-1) x kg(-1)) and 0.4% propranolol (1 mL/kg,40 microL x min(-1) x kg(-1)) under food-deprivation conditions. RESULTS: After intravenous injection of atropine and clenbuterol, the intragastric pressure were decreased significantly (P < 0.05), while after administration of Ach and propranolol, the intragastric pressure increased markedly (P < 0.05). Under normal and starvation conditions, and after intravenous administration of M-receptor antagonist (atropine) and agonist (Ach), beta-receptor antagonist (propranolol) and agonist (clenbuterol), EA stimulation of ST 25 produced an apparently inhibitory effects on gastric motility (80.00%, 86.67%, 76.67%, 86.67%, 73.33% and 86.67%, respectively) and intragatric pressure (P < 0.05) with the tendency being starvation > normal, acetylcholine > atropine and clenbuterol > propranolol. Whereas EA stimulation of LI 11 and ST 37 mainly produced an excitatory effect on gastric motility (60.00%, 56.67%, 93.33%, 40.00%, 53.33% and 50.00%, respectively for LI 11; 66.67%, 60.00%, 80.00%, 53.33%, 46.67% and 73.33%, respectively for ST 37). Following EA stimulation of the paired-acupoint groups, ST 25-ST 37 induced a predominately inhibitory effect on gastric motility (50.00%) and intragastric pressure, while LI 11-ST 37 stimulation had a principally excitatory effect on gastric motility (53.33%), and ST 25-LI 11 showed no apparent effect (50.00%). CONCLUSION: EA stimulation of ST 25 area at the abdomen produces a predominant inhibitory effect on gastric motility, while EA of LI 11 and ST 37 on the upper and lower limbs induces an excitatory effect on gastric movement, when applied in pairs, EA of ST 25-ST 37 suppresses the gastric activity, and LI 11-ST 37 promotes the gastric activity, suggesting a specificity of the effect of different acupoint stimulation.