Distally based sural flaps for soft tissue defects following traumatic osteomyelitis of lower leg and foot.

This retrospective study aimed to determine the incidence and risk factors for osteomyelitis recurrence and present our experiences in treating traumatic osteomyelitis in the lower leg and foot. We retrospectively reviewed data from 174 patients with distally based sural flaps for treating traumatic osteomyelitis with soft tissue defects in the lower leg and foot from November 2003 to February 2021. Possible risk factors for osteomyelitis recurrence were compared between the osteomyelitis control and recurrence groups. A total of 162 (93.1%) flaps survived uneventfully, while 12 (6.9%) flaps developed partial necrosis. Five patients had a bone defect with an average length of 5 cm. The free vascularized bone grafts were performed in two patients, and bone transportations were performed in three patients. All patients were followed up with an average period of 72.8 months. There were 152 patients (87.4%) in control group and 22 patients (12.6%) in recurrence group. The recurrence rates of osteomyelitis were significantly higher when the patient's age was 40 years or more and the duration was 10 weeks or more (P < 0.05). Cierny-Mader (C-M) classification type IV osteomyelitis was also significantly associated with osteomyelitis recurrence (p = 0.049). This flap combined with appropriate osteomyelitis treatment was an effective method to treat traumatic osteomyelitis of lower leg and foot with a soft tissue defect. Both patient age ≥ 40 years old and C-M type IV osteomyelitis were nonnegligible risk factors for osteomyelitis recurrence.

Increased atherosclerotic lesions in LDL receptor deficient mice with hematopoietic nuclear receptor Rev-erbα knock- down.

BACKGROUND: Nuclear receptor Rev-erbα plays important roles in circadian clock timing, lipid metabolism, adipogenesis, and vascular inflammation. However, the role of Rev-erbα in atherosclerotic lesion development has not been assessed in vivo. METHODS AND RESULTS: The nuclear receptor Rev-erbα was knocked down in mouse haematopoietic cells by means of shRNA-lentiviral transduction, followed by bone marrow transplantation into LDL receptor knockout mice. The Rev-erbα protein in peripheral macrophage was reduced by 70% as compared to control mice injected with nontargeting shRNA lentivirus-transduced bone marrow. A significant increase in atherosclerotic lesions was observed around the aorta valves as well as upon en face aorta analysis of Rev-erbα knock-down bone marrow recipients (P<0.01) as compared to the control mice, while plasma cholesterol, phospholipid, and triacylglycerol levels were not affected. Overexpression of Rev-erbα in bone marrow mononuclear cells decreased inflammatory M1 while increasing M2 macrophage markers, while Rev-erbα knock down increased the macrophage inflammatory phenotype in vitro and in vivo. Furthermore, treatment of differentiating macrophages with the Rev-erbα ligand heme promoted expression of antiinflammatory M2 markers. CONCLUSIONS: These observations identify hematopoietic cell Rev-erbα as a new modulator of atherogenesis in mice.

OSBP-related protein 8 (ORP8) regulates plasma and liver tissue lipid levels and interacts with the nucleoporin Nup62.

We earlier identified OSBP-related protein 8 (ORP8) as an endoplasmic reticulum oxysterol-binding protein implicated in cellular lipid homeostasis. We now investigated its action in hepatic cells in vivo and in vitro. Adenoviral overexpression of ORP8 in mouse liver induced a decrease of cholesterol, phospholipids, and triglycerides in serum (-34%, -26%, -37%, respectively) and liver tissue (-40%, -12%, -24%), coinciding with reduction of nuclear (n)SREBP-1 and -2 and mRNA levels of their target genes. Consistently, excess ORP8 reduced nSREBPs in HuH7 cells, and ORP8 overexpression or silencing by RNA interference moderately suppressed or induced the expression of SREBP-1 and SREBP-2 target genes, respectively. In accordance, cholesterol biosynthesis was reduced by ORP8 overexpression and enhanced by ORP8 silencing in [(3)H]acetate pulse-labeling experiments. ORP8, previously shown to bind 25-hydroxycholesterol, was now shown to bind also cholesterol in vitro. Yeast two-hybrid, bimolecular fluorescence complementation (BiFC), and co-immunoprecipitation analyses revealed the nuclear pore component Nup62 as an interaction partner of ORP8. Co-localization of ORP8 and Nup62 at the nuclear envelope was demonstrated by BiFC and confocal immunofluorescence microscopy. Furthermore, the impact of overexpressed ORP8 on nSREBPs and their target mRNAs was inhibited in cells depleted of Nup62. Our results reveal that ORP8 has the capacity to modulate lipid homeostasis and SREBP activity, probably through an indirect mechanism, and provide clues of an entirely new mode of ORP action.