LRG1 inhibits hepatic macrophage activation by enhancing TGF-β1 signaling to alleviate MAFLD in mice / 南方医科大学学报

OBJECTIVE@#To explore the effect of leucine-rich α-2-glycoprotein (LRG1) derived from hepatocytes on activation of hepatic M1 Kupffer cells.@*METHODS@#A metabolic dysfunction-associated fatty liver disease (MAFLD) model was established in BALB/c mice by high-fat diet (HFD) feeding for 16 weeks. Oleic acid was used to induce steatosis in primary cultures of mouse hepatocytes. The mRNA and protein expressions of LRG1 in mouse liver tissues and hepatocytes were detected by real-time PCR and Western blotting. Primary hepatic macrophages were stimulated with the conditioned medium (CM) from steatotic hepatocyte along with LRG1 or transforming growth factor-β1 (TGF-β1), or both for 24 h, and the expression levels of inducible nitric oxide synthase (iNOS) was detected with Western botting, and the mRNA expressions of iNOS, chemokine ligand 1 (CXCL-1) and interleukin-1β (IL-1β) were measured by RT-PCR. The MAFLD mice were injected with LRG1 (n=6), TGF-β1 (n=6), or both (n=6) through the caudal vein, and the live tissues were collected for HE staining and immumohistochemical detection of F4/80 expression; the mRNA expressions of iNOS, CXCL-1 and IL-1β in liver tissues were detected using RT-PCR.@*RESULTS@#The mRNA and protein expression levels of LRG1 were significantly downregulated in the liver tissues of MAFLD mice and steatotic hepatocytes (P < 0.05). Treatment of the hepatic macrophages with CM from steatosis hepatocytes significantly enhanced the mRNA expression levels of iNOS, CXCL-1 and IL-1β, and these changes were significantly inhibited by the combined treatment with TGF-β1 and LRG1 (P < 0.05). In MAFLD mice, injections with either LRG1 or TGF-β1 alone reduced hepatic lipid deposition and intrahepatic macrophage infiltration, and these effects were significantly enhanced by their combined treatment, which also more strongly inhibited the mRNA expression levels of iNOS, CXCL-1 and IL-1β (P < 0.05).@*CONCLUSION@#LRG1 inhibits hepatic macrophage infiltration by enhancing TGF-β1 signaling to alleviate fatty liver inflammation in MAFLD mice.

Preventing ankle instability through exercise：A meta-analysis / 中华物理医学与康复杂志

Objective To explore the effect and mechanism of preventing ankle instability through exer-cise, so as to provide evidence-based references for practice. Methods The randomized and controlled trials ( RCT) on preventing ankle instability through exercise published before December 2014 were searched for in the NCBI, CNKI, VIP and Wanfang databases by computer, supplemented by manual searching. Each study′s quality was evaluated according to the standards of the Cochrane handbook by 3 researchers. The outcome indexes were ex-tracted and analyzed using RevMan 5.2 software. Results After the initial selection, 665 papers (357 in English and 308 in Chinese) were retained. From these 92 were chosen after reading the titles and abstracts. Ultimately, 14 RCT studies ( 12 in English and 2 in Chinese) met the inclusion criteria. They showed that exercise improved ankle function and symptoms of ankle instability significantly [SMD=0.98, 95%CI (0.65,1.31), P≤0.01], improved muscle strength [SMD=1.50, 95%CI (0.99,2.01), P≤0.01], improved balance and postural stability [SMD=-0.54, 95%CI (-0.84,-0.25) ,P≤0.01] , but did not improve proprioception or neuromuscular functioning sig-nificantly. Conclusions Exercise can effectively improve muscle strength, balance and postural stability, but not proprioception or neuromuscular functioning. The details of these findings may be related to the exercise intervention chosen.