MiR-21 inhibitor improves locomotor function recovery by inhibiting IL-6R/JAK-STAT pathway-mediated inflammation after spinal cord injury in model of rat.

OBJECTIVE: To investigate the function of miRNA-21 and interleukin-6 receptor/Janus Kinase-Signal transducer and activator of transcription (IL-6R/JAK-STAT) pathway in microglia on inflammatory responses after spinal cord injury (SCI). MATERIALS AND METHODS: This study first detected respectively the protein level of inflammatory factor inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α) by Western blotting after transfection of miR-21 or administration of miR-21 inhibitor in activated microglia cells of rat in vitro. The quantitative Real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of IL-6R under two different interventions. Next, we established a model of spinal cord injury in rat and inspected miR-21 and IL-6R in SCI rat by qRT-PCR. In addition, the protein levels of iNOS and TNF-α in SCI rat were detected by Western blotting. MiR-21 inhibitor was injected into the injured area of SCI rat to delve into the function of miR-21 down-expression on iNOS and TNF-α expression by Western blot as well as the RNA levels of IL-6R, JAK and STAT3 by qRT-PCR. Furthermore, the SCI rat with movement and coordination of hindlimbs was observed by Basso-Beattie-Bresnahan locomotor rating scale (BBB scale) after miR-21 down-expression. RESULTS: Compared with the microglia transfected with miR-21, the execution of inhibitor in microglia effectively relieved the expression of IL-6R and the breakout of iNOS and TNF-α. Meanwhile, the increase of miR-21 was significantly observed in SCI rat along with significant improvement of inflammatory response-related factors including iNOS and TNF-α. After that, we injected SCI rat with miR-21 inhibitor into the spinal cord injury area and found the inhibition of miR-21 decreased the protein levels of iNOS and TNF-α. Simultaneously, down-expression of miR-21 evidently declined the RNA levels of IL-6R, JAK, and STAT3 in SCI rat. Compared with the sham-operated rat, the movement and coordination of hindlimbs of the SCI group displayed dramatic dysfunction. However, miR-21 down-expression elevated the movement and coordination of hindlimbs of the SCI rat than those of the only injury group. CONCLUSIONS: Inhibition of miR-21 can promote the recovery of spinal cord injury by down-regulating IL-6R/JAK-STAT signaling pathway and inhibiting inflammation.

Clinical Outcomes of Patients with Severe Hepatic Hereditary Hemorrhagic Telangiectasia After Banding of the Hepatic Artery and Banding/Ligation of Branches of the Hepatic Artery.

OBJECTIVE/BACKGROUND: To evaluate the effectiveness of double banding/ligation of hepatic arteries in treating patients with hepatic hereditary hemorrhagic telangiectasia (HHHT). METHODS: From January 2004 to December 2013, 35 patients were diagnosed with HHHT, among whom 11 woman and two men with a mean ± SD age of 44 ± 9 years were treated by double hepatic artery banding/ligation for cardiac insufficiency and/or portal hypertension. The outcomes were evaluated prospectively by measuring clinical manifestations, imaging features, liver and cardiac function, pulmonary arterial systolic pressure, and post-operative complications. Quality of life was evaluated with the Short Form Health Survey questionnaire. RESULTS: For each patient, the common hepatic artery and one branch of the left and/or right hepatic artery were banded, and other significantly dilated hepatic artery branches were ligated. No patient died after surgery. Clinical symptoms were improved in all patients, although ischemic cholangitis was observed in two patients and treated conservatively. Cardiac function, classified per the New York Heart Association (NYHA) cardiac functional grading, improved (NYHA III-IV vs. NYHA I-II); pulmonary arterial systolic pressure significantly decreased in all patients (48 ± 8 mmHg vs. 24 ± 4 mmHg; P < .001) and remained in the normal range (26 ± 3 mmHg) at the end of follow up. The levels of γ-glutamyl transpeptidase and alkaline phosphatase decreased in 11 patients (144 ± 94 U/L vs. 71 ± 34 U/L; P = .003) and 10 patients (207 ± 71 U/L vs. 105 ± 32 U/L; P = .001), respectively. Patients were followed up for 50 ± 28 months (range 6-113 months); one death resulted from causes unrelated to surgery and all dimensions of quality of life improved in all surviving patients. CONCLUSIONS: This study helps to establish double hepatic artery banding/ligation as an effective therapy for selected patients with HHHT.