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Background: Achilles tendon (AT) midsubstance injuries may heal suboptimally, especially in athletes. Transforming growth factor–beta 3 (TGF-β3) shows promise because of its recently discovered tendinogenic effects. Using poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) may enhance the results by a sustained-release effect. Hypothesis: The application of TGF-β3 will enhance AT midsubstance healing, and the NP form will achieve better outcomes. Study Design: Controlled laboratory study. Methods: A total of 80 rats underwent unilateral AT transection and were divided into 4 groups: (1) control (C); (2) empty chitosan film (Ch); (3) chitosan film containing free TGF-β3 (ChT); and (4) chitosan film containing TGF-β3–loaded NPs (ChN). The animals were sacrificed at 3 and 6 weeks. Tendons were evaluated for morphology (length and cross-sectional area [CSA]), biomechanics (maximum load, stress, stiffness, and elastic modulus), histology, immunohistochemical quantification (types I and III collagen [COL1 and COL3]), and gene expression (COL1A1, COL3A1, scleraxis, and tenomodulin). Results: Morphologically, at 3 weeks, ChT (15 ± 2.7 mm) and ChN (15.6 ± 1.6 mm) were shorter than C (17.6 ± 1.8 mm) ( P = .019 and = .004, respectively). At 6 weeks, the mean CSA of ChN (10.4 ± 1.9 mm2) was similar to that of intact tendons (6.4 ± 1.1 mm2) ( P = .230), while the other groups were larger. Biomechanically, at 3 weeks, ChT (42.8 ± 4.9 N) had a higher maximum load than C (27 ± 9.1 N; P = .004) and Ch (29.2 ± 5.7 N; P = .005). At 6 weeks, ChN (26.9 ± 3.9 MPa) had similar maximum stress when compared with intact tendons (34.1 ± 7.8 MPa) ( P = .121); the other groups were significantly lower. Histologically, at 6 weeks, the mean Movin score of ChN (4.5 ± 1.5) was lower than that of ChT (6.3 ± 1.8). Immunohistochemically, ChN had higher COL3 (1.469 ± 0.514) at 3 weeks and lower COL1 (1.129 ± 0.368) at 6 weeks. COL1A1 gene expression was higher in ChT and ChN at 3 weeks, but COL3A1 gene expression was higher in ChN. Conclusion: The application of TGF-β3 had a positive effect on AT midsubstance healing, and the sustained-release NP form improved the outcomes, more specifically accelerating the remodeling process. Clinical Relevance: This study demonstrated the effectiveness of TGF-β3 on tendon healing on a rat model, which is an important step toward clinical use. The novel method of using PLGA-b-PEG NPs as a drug-delivery system with sustained-release properties had promising results.

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The aim of this study was to investigate the possible effects of melatonin on rat uterine tissue against exposure with bisphenol A (BPA) in the neonatal period. Twenty-four female rats were divided into four groups, (n=6) per group. Group I was used as a control (sesame oil + ethanol), group II was injected daily with (100 mg/kg) BPA by subcutaneously (sc) daily postnatal days (PND 0-10), group III was injected daily with (10 mg/kg) melatonin by sc for 10 days (PND 20-30), and group IV was injected daily with (100 mg/kg) BPA (PND 0-10) and (10 mg/kg) melatonin (PND 20-30). All rats were sacrificed in the same day of metestrus cycle, approximately PND 70. Histological analyses, immunostaining of B cell lymphoma 2 (Bcl-2), and cytochrome c and TUNEL assays were performed. According to our results, neonatal exposure to BPA accelerates onset of puberty, causes degenerative and morphometric changes on rat uterus, and increases apoptotic reaction rates. The immunoreactivity of Bcl-2 was decreased after BPA administration. In addition, immunoreactivity of Bcl-2 showed an increase after melatonin treatment. However, cytochrome c immunoreactivity was decreased after melatonin administration. Our results suggest that melatonin may have positive effects against BPA-induced degenerative changes on rat uterus.