Correlation of expression of silencing information regulator 2 related enzyme 1 and tumor necrosis factor-like weak inducer of apoptosis in articular effusion and knee osteoarthritis / 中国骨伤

OBJECTIVE@#To analyze the correlation between the expression of silencing information regulator 2 related enzyme 1 (SIRT1), tumor necrosis factor like weak inducer of apoptosis (TWEAK) and knee osteoarthritis.@*METHODS@#Total of 103 patients with knee joint (knee osteoarthritis group) from February 2019 to August 2021 were selected including 40 males and 63 females with an average age of (62.02±6.09) years;according to the modified Mankin score, 103 patients were divided into mild group (Mankin score 1-4 points, 31 cases) and moderate group (Mankin score 5-8 points, 40 cases) and severe group (Mankin score ≥9, 32 cases). Another 105 physical examination volunteers were selected as the control group including 46 males and 59 females with an average age of (62.11±6.34) years old. The levels of SIRT1 and TWEAK in articular effusion and serum were detected in the knee osteoarthritis group, while serum SIRT1 and TWEAK were detected in the control group only. The relationship between SIRT1, TWEAK and the occurrence and disease of knee osteoarthritis were analyzed.@*RESULTS@#Articular cavity fluid TWEAK, serum TWEAK, CRP, IL-6, IL-1β, white blood cell count and ESR were higher than those in the control group(P<0.05), articular cavity fluid SIRT1 and serum SIRT1 were lower than those in the control group(P<0.05). TWEAK level in the severe group was higher than that in the moderate and mild groups(P<0.05), SIRT1 was lower than that in the moderate and mild groups (P<0.05). The level of SIRT1 in articular cavity effusion was positively correlated with the serum level of SIRT1 (P<0.05), and negatively correlated with CRP, IL-6, IL-1β, white blood cell count, modified Mankin score and ESR (P<0.05). TWEAK level in articular cavity fluid was positively correlated with serum TWEAK level (P<0.05), C-reactive protein(CRP), interleukin(IL)-6, IL-1β, white blood cell count, modified Mankin score and erythrocyte sedimentation rate(ESR) (P<0.05). Body mass index, undertaking heavy physical work, and articular cavity fluid TWEAK were risk factors for the occurrence of knee osteoarthritis(P<0.05), and articular cavity fluid SIRT1 was a protective factor for the occurrence of knee arthritis (P<0.05). The area under curve(AUC) of SIRT1 and TWEAK for knee osteoarthritis was 0.641 and 0.653, and the AUC of SIRT1 and TWEAK for knee osteoarthritis was 0.879, which was higher than SIRT1 and TWEAK alone (z=6.105 and 6.225, P<0.05).@*CONCLUSION@#The level of SIRT1 in articular fluid in patients with knee arthritis is decreased and the level of TWEAK is increased. Low SIRT1 and high TWEAK are associated with the onset and exacerbation of knee osteoarthritis.

Mechanism of TWEAK promoting macrophage-derived exosomal miR-7 to epithelial ovarian cancer cell through regulating Dicer / 上海交通大学学报（医学版）

Objective • To investigate the mechanism of tumor necrosis factor like weak inducer of apoptosis (TWEAK) promoting macrophagederived exosomal miR-7 to epithelial ovarian cancer (EOC). Methods • The expression of Dicer was detected by real-time PCR and Western blotting in TWEAK-stimulated macrophages. The expression of miR-7 was detected by real-time PCR in the macrophage and macrophage-derived exosome after silencing Dicer in macrophage. While in Dicer-overexpressing macrophage, real-time PCR was used to detect the expression of miR-7. Then TWEAK was used to stimulate the macrophage, and the expression of miR-7 in the macrophage and macrophage-derived exosome was detected by real-time PCR. The expression of key proteins in the nuclear factor-κB (NF-κB) pathway was detected by Western blotting in TWEAK-stimulated macrophage. After pretreatment of NF-κB inhibitor, Western blotting was used to detect the expression of Dicer and key proteins in the NF-κB pathway in TWEAKstimulated macrophage. Results • The expression of Dicer in macrophage was down-regulated after TWEAK stimulating. The expression of miR-7 was up-regulated in Dicer-silencing macrophage and macrophage-derived exosome. While the expression of miR-7 was down-regulated in the macrophage and the macrophage-derived exosome in Dicer-overexpressing macrophage after TWEAK stimulating. The expression of key proteins in the NF-κB pathway in macrophage was also up-regulated after TWEAK stimulating. After inhibition of NF-κB signaling pathway, the expression of Dicer was not significantly changed in TWEAK-stimulated macrophage compared to the control group. Conclusion • TWEAK can active NF-κB pathway and inhibit the expression of Dicer to promote macrophage-derived exosomal miR-7 to EOC cells.