Comparative analysis of supercritical fluid-based and chemical-based decellularization techniques for nerve tissue regeneration.

Axon regeneration and Schwann cell proliferation are critical processes in the repair and functional recovery of damaged neural tissues. Biomaterials can play a crucial role in facilitating cell proliferative processes that can significantly impact the target tissue repair. Chemical decellularization and supercritical fluid-based decellularization methods are similar approaches that eliminate DNA from native tissues for tissue-mimetic biomaterial production by using different solvents and procedures to achieve the final products. In this study, we conducted a comparative analysis of these two methods in the context of nerve regeneration and neuron cell differentiation efficiency. We evaluated the efficacy of each method in terms of biomaterial quality, preservation of extracellular matrix components, promotion of neuronal cell differentiation and nerve tissue repair ability in vivo. Our results indicate that while both methods produce high-quality biomaterials, supercritical fluid-based methods have several advantages over conventional chemical decellularization, including better preservation of extracellular matrix components and mechanical properties and superior promotion of cellular responses. We conclude that supercritical fluid-based methods show great promise for biomaterial production for nerve regeneration and neuron cell differentiation applications.

Decellularized brain extracellular matrix based NGF-releasing cryogel for brain tissue engineering in traumatic brain injury.

Traumatic brain injuries(TBI) pose significant challenges to human health, specifically neurological disorders and related motor activities. After TBI, the injured neuronal tissue is known for hardly regenerated and recovered to their normal neuron physiology and tissue compositions. For this reason, tissue engineering strategies that promote neuronal regeneration have gained increasing attention. This study explored the development of a novel neural tissue regeneration cryogel by combining brain-derived decellularized extracellular matrix (ECM) with heparin sulfate crosslinking that can perform nerve growth factor (NGF) release ability. Morphological and mechanical characterizations of the cryogels were performed to assess their suitability as a neural regeneration platform. After that, the heparin concnentration dependent effects of varying NGF concentrations on cryogel were investigated for their controlled release and impact on neuronal cell differentiation. The results revealed a direct correlation between the concentration of released NGF and the heparin sulfate ratio in cryogel, indicating that the cryogel can be tailored to carry higher loads of NGF with heparin concentration in cryogel that induced higher neuronal cell differentiation ratio. Furthermore, the study evaluated the NGF loaded cryogels on neuronal cell proliferation and brain tissue regeneration in vivo. The in vivo results suggested that the NGF loaded brain ECM derived cryogel significantly affects the regeneration of brain tissue. Overall, this research contributes to the development of advanced neural tissue engineering strategies and provides valuable insights into the design of regenerative cryogels that can be customized for specific therapeutic applications.

Pin1 plays a critical role as a molecular switch in canonical BMP signaling.

Pin1 is a peptidyl prolyl cis-trans isomerase that specifically binds to the phosphoserine-proline or phosphothreonine-proline motifs of numerous proteins. Previously, we reported that Pin1 deficiency resulted in defects in osteoblast differentiation during early bone development. In this study, we found that adult Pin1-deficient mice developed osteoporotic phenotypes compared to age-matched controls. Since BMP2 stored in the bone matrix plays a critical role in adult bone maintenance, we suspected that BMP R-Smads (Smad1 and Smad5) could be critical targets for Pin1 action. Pin1 specifically binds to the phosphorylated linker region of Smad1, which leads to structural modification and stabilization of the Smad1 protein. In this process, Pin1-mediated conformational modification of Smad1 directly suppresses the Smurf1 interaction with Smad1, thereby promoting sustained activation of the Smad1 molecule. Our data demonstrate that post-phosphorylational prolyl isomerization of Smad1 is a converging signal to stabilize the Smad1 molecule against the ubiquitination process mediated by Smurf1. Therefore, Pin1 is a critical molecular switch in the determination of Smad1 fate, opposing the death signal transmitted to the Smad1 linker region by phosphorylation cascades after its nuclear localization and transcriptional activation. Thus, Pin1 could be developed as a major therapeutic target in many skeletal diseases.

Prognostic factors for pulmonary metastasectomy in the treatment of hepatocellular carcinoma.

BACKGROUND: This study aimed to present our experience with pulmonary metastasectomy in the treatment of hepatocellular carcinoma and to evaluate the prognostic factors. METHODS: The clinicopathologic data of 17 patients including presence of viral hepatitis, the serum alpha-fetoprotein (AFP) level, the number of metastases, and laterality were analyzed. The overall survival rates and the prognostic factors were estimated using the Kaplan-Meier method and Cox proportional hazards model for multivariate analysis. RESULTS: The median follow-up periods after pulmonary resection and initial hepatic resection were 28.9 and 46.2 months, respectively. The actuarial overall 1-, 3-, and 5-year survival rates after pulmonary metastasectomy were 64.7 +/- 11.6%, 29.4 +/- 11.1%, and 11.8 +/- 7.8%, respectively. Using multivariate analysis, disease-free interval (DFI) of more than 24 months (hazard ratio = 2.36, 95% confidence interval = 1.33-25.33, p = 0.020) and AFP levels after pulmonary resection (hazard ratio = 51.3 95% confidence interval = 3.68-716.66, p = 0.003) were found to be independent prognostic factors. CONCLUSIONS: Although only a small number of patients were enrolled in this study, a disease-free interval more than 24 months and the serum AFP level after pulmonary metastasectomy might be important prognostic factors.

Primary esophageal repair in Boerhaave's syndrome.

Boerhaave's syndrome is the most severe disease in the esophageal perforation. The purpose of this report is to evaluate the outcome in patients who were treated with primary repair for Boerhaave's syndrome regardless of the time interval. From 1997 to July 2007, 10 patients with Boerhaave's syndrome were treated with primary repair regardless of the time interval. The interval between rupture and initial treatment was less than 24 hours in five patients (50.0%) and more than 24 hours in the other five patients (50.0%). There was no operative mortality and five postoperative leaks. Of these five patients with postoperative leaks, one received primary repair for less than 24 hours (20%) and four received operation for more than 24 hours (80%). However, postoperative leaks were managed by non-operative methods and resolved within 2 weeks. The time interval between perforation and operative intervention should not prejudice the surgeon against primary repair of Boerhaave's syndrome. Although a high incidence of postoperative leak occurred in patients who were operated on for more than 24 hours, its management is not hard to perform and its prognosis was not poor.