Glutamine exerts a protective effect on osteoarthritis development by inhibiting the Jun N-terminal kinase and nuclear factor kappa-B signaling pathways.

Strategies for treating osteoarthritis (OA) have become a research focus because an effective treatment for OA is unavailable. The objective of this study was to explore the effects and underlying mechanisms of glutamine (Gln) in OA. First, the chondrocytes were identified and a standard IL-1ß-induced OA model was established. After treatment with Gln or saline, the viability and apoptosis of chondrocytes were evaluated using a CCK-8 assay and flow cytometry analysis, which revealed that Gln can improve the IL-1ß-induced OA cells. Meanwhile, Gln can enhance the expression of aggrecan and collagen II, which are protective proteins for articular cartilage. Instead, Gln inhibited the expression of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13), which can degrade cartilage. To better understand the underlying mechanisms of Gln in IL-1ß-induced chondrocytes, the classical OA pathways of JNK and NF-κB were examined at the protein and mRNA levels using western blot and qRT-PCR analyses. We found that JNK and NF-κB were downregulated gradually depending on the Gln dose and protective and destructive factors changed based on changes of JNK and NF-κB. The effects of high-dose Gln were more effective than low-dose. Moreover, Gln was applied to the animal OA model to check the effects in vivo. The results showed that Gln attenuated cartilage degeneration and decreased OARSI scores, which demonstrated that Gln can improve OA. The experiments showed that Gln can benefit mice with OA by inhibiting the JNK and NF-κB signaling pathways.

Modified donor blood flow-preserved cross-leg anterolateral thigh flap procedure for complex lower extremity reconstruction.

BACKGROUND: Complex lower limb reconstruction due to severe trauma remains a challenge for reconstructive surgeons. Here, we introduce a modified donor blood flow-preserved cross-leg anterolateral thigh flap procedure and evaluate its clinical efficacy. METHODS: Between January 2013 and December 2019, 22 patients (range 10 to 64 years old) with unilateral lower limb injury underwent modified donor blood flow-preserved cross-leg anterolateral thigh flap procedures. Among them, 16 cases were traffic accidents, 5 cases were persistent ulcers, and 1 case was a degloving injury. The arterial pedicle of the flap was prepared in a Y-shaped fashion and microanastomosed to the posterior tibial artery of intact leg in a flow-through style. A split-thickness skin graft was applied to wrap the vascular pedicle after anastomosis. The flap was designed in a single or bilobed fashion according to the shape of the tissue defect. The operation time, the intraoperative blood loss and the length of hospital stays were recorded. The vascular pedicle was divided 4 weeks after anastomosis. Doppler ultrasound was performed to evaluate the blood flow of the donor posterior tibial artery during postoperative follow-up. RESULTS: All 22 flaps survived. The tissue defects ranged from 12 × 6 to 21 × 18 cm2. The flap sizes ranged from 14 × 7.5 to 24 × 21 cm2. The average operation time, intraoperative blood loss and length of hospital stays were 6.73 ± 1.49 h, 280.95 ± 59.25 ml and 30.55 ± 2.52 days, respectively. Eighteen flaps were designed in a single fashion, while four were in bilobed fashion. Twenty patients underwent fasciocutaneous flap transplantations, while two underwent musculocutaneous flap transplantations. Two cases developed local lysis of the flap which healed after further debridement. Direct suture of the incision after flap harvest was performed in 16 cases, while additional full-thickness skin grafting was performed in the remaining 6 cases. Further bone transport procedures were performed in 15 patients who had severe tibia bone defects. The blood flow of donor posterior tibial artery was confirmed in all patients during follow-ups. All patients recovered flap sensation at the final follow-up. The postoperative follow-ups ranged from 18 to 84 months, and no long-term complications were observed. CONCLUSIONS: The modified donor blood flow-preserved cross-leg anterolateral thigh flap procedure is an ideal method to repair severe lower limb trauma with tibial artery occlusion which avoids sacrificing the major artery of the uninjured lower limb.

Identification of the Fosl1/AMPK/autophagy axis involved in apoptotic and inflammatory effects following spinal cord injury.

Strategies for reducing spinal cord injury (SCI) have become a research focus because an effective treatment of SCI is unavailable. The objective of this study was to explore the underlying mechanisms of Fosl1 following SCI. Based on the analysis of the Gene Expression Omnibus (GEO) database, Fosl1 was found to be highly enhanced in SCI. This result was confirmed in our animal model, and Fosl1 was found to be obviously expressed in neurons. Next, we treated PC-12 cells with H2O2 to mimic injured neurons and further verified that Fosl1 silencing upregulated AMPK expression, promoted autophagy and inhibited inflammation and apoptosis. Subsequently, a special inhibitor of AMPK was used to examine the role of AMPK, and we learned that the inhibition of AMPK suppressed autophagy and promoted inflammation and apoptosis following Fosl1 silencing. These changes completely reversed the beneficial effects of Fosl1 silencing on injured PC-12 cells. Moreover, treatment with an AMPK activator resulted in effects that were opposite those of the inhibitor. Finally, rats were injected intrathecally with si-Fosl1 to detect its role in vivo. The results showed that si-Fosl1 improved neurological function and decreased apoptosis and inflammation at 14 d postoperation, and the activator further benefited the rats of si-Fosl1 treatment. In conclusion, Fosl1 inhibits autophagy and promotes inflammation and apoptosis through the AMPK signaling pathway following SCI in vivo and in vitro.