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Background and Objectives@#Despite advances in wound treatments, chronic diabetic wounds remain a significant medi-cal challenge. Exosomes from mesenchymal stem cells (MSCs) and small molecule activators of nuclear factor erythroid 2–related factor 2 (Nrf2) have emerged as potential therapies for nonhealing diabetic wounds. This study aimed to evaluate the effects of exosomes from bone marrow-derived MSCs (BMSCs) alone, or in combination with a small molecule activator of Nrf2 on diabetic wound healing. @*Methods@#and Results: BMSCs and endothelial progenitor cells (EPCs) were isolated from the femur and tibia bone marrow of Sprague-Dawley (SD) rats and culture-expanded. Exosomes were harvested from the BMSC culture supernatants through ultracentrifugation. The effects of the exosomes and Nrf2 knockdown, alone or in combination, on EPC tube formation were evaluated. Streptozotocin-induced diabetic rats bearing a fresh full-thickness round wound were treated with the exosomes alone, or in combination with a lentiviral shRNA targeting Nrf2 (Lenti-sh-Nrf2) or tert-butylhydroquinone (tBHQ), a small molecule activator of Nrf2. Two weeks later, wound closure, re-epithelization, collagen deposition, neovascularization, and local inflammation were evaluated. BMSC exosomes promoted while Nrf2 knockdown inhibited EPC tube formation. BMSC exosomes accelerated wound closure, re-epithelization, collagen deposition, and neovascularization, and reduced wound inflammation in diabetic rats. These regenerative and anti-inflammatory effects of the exosomes were inhibited by Lenti-sh-Nrf2 but enhanced by tBHQ administration. @*Conclusions@#BMSC exosomes in combination with a small molecule Nrf2 activator hold promise as a new therapeutic option for chronic diabetic wounds.
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BACKGROUND: Functional dressings have been widely used in clinical practice, but so far none of existing dressings can meet the clinical needs in terms of gas permeability, biocompatibility, comfort, and degradability. OBJECTIVE: To systemically evaluate the biosafety properties of water-soluble chitosan lactate/hyaluronan sponge after modification. METHODS: In the study, there were 10 male BALB/C mice of SPF grade (6-8 weeks old), 20 Sprague-Dawley rats of SPF grade (7 weeks old, both genders), and 3 male New Zealand white rabbits (8 weeks old), all provided by Dongguan Songshanhu Pearl Animal Technology Co., Ltd. The chitosan lactate/hyaluronan sponge was prepared for cytotoxicity test. A blank control group was set. According to the GB/T16886 biological evaluation system, the rabbits were subjected to composite sponge stimulation and sensitization and intradermal reaction tests from the perspective of biosafety, and then divided into non-polar extract group, polar extract group and negative control group. The inoculation site was observed within 72 hours. The mice were subjected to acute toxicity test, and divided into experimental group (extraction solution) and control group (pure saline), and their manifestations were observed for 72 hours. The rats were subjected to subchronic toxicity test, and then divided into experimental group (subcutaneous implantation of composite sponge) and control group (making a skin incision on the back followed by suturing). The changes in body weight of the rats were observed, blood samples from the rats were taken intravenously for blood routine analysis at 13 weeks after testing, and the rats were anesthetized and executed in the next day for gross observations of the heart, liver, spleen, kidney, brain, pancreas, thymus, stomach, and bladder. RESULTS AND CONCLUSION: (1) The chemical structure of the modified composite sponge formed as expected. The cytotoxicity of the composite sponge was grade 1, which was not significantly different from the negative control group. (2) The skin irritation test showed no skin erythema and edema in the New Zealand white rabbits after being stimulated by the composite sponge, and the existing stimulation reactions were extremely mild. Almost no obvious sensitization reaction occurred. (3) No erythema and edema were captured in the intradermal reaction test, and intradermal reaction stimulation of the composite sponge was very weak. (4) In the acute toxicity test, no obvious toxicity symptoms such as hypocinesis, dyspnea and abdominal stimulation were observed in the mice. Furthermore, at the observational time point of 72 hours, no acute systemic toxicity occurred in the two groups. (5) In the subchronic toxicity test, no obvious difference was detected in the rat body mass between the experimental and control groups. The same conclusion was made in the hematology and organ coefficient tests. To conclude, the chitosan lactate/hyaluronate sponge has excellent biological properties and good biosafety, which can be applied for further clinical use.
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Objective To study effects of different types of high-impact exercises on the increment of bone mineral density (BMD) and bone mineral content (BMC) . Methods Thirty-nine male volunteers, including 13 hoopsters, 13 paratroopers, and 13 common college students as the control, were recruited and divided into two subgroups (subgroup 1:20-22 years old; subgroup 2:23-25 years old). Their BMDs and BMCs on calcaneus, first through fifth metatarsus, hip, and lumbar spine (L1-4) were evaluated. Results The BMC of calcaneus, the first and second metatarsals, total lumbar spine, and total hip in the hoopster group was significantly higher than that in the control group and paratrooper group. The hoopster group obtained statistically higher BMD at the lumbar spine, hip, and femoral neck than the other two groups. However, the BMCs and BMDs of the paratrooper group and control group had no significant differences at almost all measured anatomical locations. Conclusions BMC and BMD are not always in positive correlation with vertical ground reaction forces during normal exercises. Compared with parachuting training, playing basketball as a kind of variable load exercise can effectively increase BMC and BMD, and is more beneficial for reducing the risk of osteoporotic fracture.
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0.05). No loosening, distortion and breaking of fusion apparatus were found. Conclusion STT arthrodesis simulated in new fusion apparatus does not show displaced even though forced the utmost movement in range of motion of extension 35?/flexion 50?, radial deviation 10?/ulnar deviation 30?. STT arthrodesis can get excellent stability using new fusion apparatus.