Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disease commonly found among elderly. In addition to cognitive and behavioral deficits, vision abnormalities are prevalent in AD patients. Recent studies investigating retinal changes in AD double-transgenic mice have shown altered processing of amyloid precursor protein and accumulation of β-amyloid peptides in neurons of retinal ganglion cell layer (RGCL) and inner nuclear layer (INL). Apoptotic cells were also detected in the RGCL. Thus, the pathophysiological changes of retinas in AD patients are possibly resembled by AD transgenic models. The retina is a simple model of the brain in the sense that some pathological changes and therapeutic strategies from the retina may be observed or applicable to the brain. Furthermore, it is also possible to advance our understanding of pathological mechanisms in other retinal degenerative diseases. Therefore, studying AD-related retinal degeneration is a promising way for the investigation on (1) AD pathologies and therapies that would eventually benefit the brain and (2) cellular mechanisms in other retinal degenerations such as glaucoma and age-related macular degeneration. This review will highlight the efforts on retinal degenerative research using AD transgenic mouse models.
Glioblastoma is a common malignant brain tumor and it is refractory to therapy because it usually contains a mixture of cell types. The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has been shown to induce apoptosis in a range of tumor cell types. Previously, we found that two human glioblastoma cell lines are resistant to TRAIL, while lovastatin sensitizes these glioblastoma cells to TRAIL-induced cell death. In this study, we investigated the mechanisms underlying the TRAIL-induced apoptosis in human glioblastoma cell lines by lovastatin. Furthermore, we have confirmed the anti-tumor effect of combination therapy with lovastatin and TRAIL in the subcutaneous brain tumor model. We showed that lovastatin significantly up-regulated the expression of death receptor 5 (DR5) in glioblastoma cell lines as well as in tumor-bearing mice with peri-tumoral administration of lovastatin. Further study in glioblastoma cell lines suggested that lovastatin treatment could inhibit NF-κB and Erk/MAPK pathways but activates JNK pathway. These results suggest that lovastatin sensitizes TRAIL-induced apoptosis by up-regulation of DR5 level via NF-κB inactivation, but also directly induces apoptosis by dysregulation of MAPK pathway. Our in vivo study showed that local peri-tumoral co-injection of lovastatin and TRAIL substantially reduced tumor growth compared with single injection of lovastatin or TRAIL in subcutaneous nude mice model. This study suggests that combined treatment of lovastatin and TRAIL is a promising therapeutic strategy to TRAIL-resistant glioblastoma.
A crude methanol extract of the herb Davallina Orientalis was given intraperitoneally to test its effect on bone healing in mice. The results indicated that it could increase the breaking strength of a fracture site. In our experimental model, the lower dosage has a better result probably because of less toxicity.
Objective To evaluate the diagnostic accuracy of frameless stereotactic brain biopsy, compare it with the current international standard, and review the era for improvement. Background The diagnostic accuracy of frameless stereotactic brain biopsy has been reported but there is limited literature focusing on the reasons for non-diagnostic cases. Methods: This is a retrospective analysis of consecutive, prospectively collected frameless stereotactic brain biopsy procedures from 2007 to 2020. We evaluated the diagnostic accuracy of the frameless stereotactic brain biopsy procedures using structurally-defined criteria. The biopsy result was classified as conclusive, inconclusive, or negative, based on the pathological, radiological, and clinical diagnosis concordance. For inconclusive or negative results, we further evaluated the preoperative planning and postoperative imaging to review the errors. A literature review for the diagnostic accuracy of frameless stereotactic biopsy was performed for the validity of our results. The objective of the study is to identify the causes of non-diagnostic results for future improvement. Results: There were 106 patients with 109 biopsy procedures performed from 2007 to 2020. The conclusive diagnosis was reached in 103 (94.5%) procedures. The inconclusive diagnosis was noted in four (3.7%) procedures and the negative biopsy was yielded in two (1.9%) procedures. Symptomatic hemorrhage was noted in one patient (0.9%). There was no mortality case (0.0%) in our series. The registration error and inaccurate targeting occurred in three trigonal lesions (2.8%), sampling of the non-representative part of the lesion occurred in two cases (1.8%), and one biopsy (0.9%) for lymphoma was negative due to the commencement of steroids. The literature review suggested that our diagnostic accuracy under the structurally-defined diagnosis criteria was comparable with the published literature, while the causes for non-diagnostic cases were uniquely performed and summarized. Conclusion: The stereotactic biopsy is a safe procedure with high diagnostic accuracy only if meticulous preoperative planning and careful intraoperative registration is performed. The common pitfalls precluding a conclusive diagnosis are registration errors and biopsies at non-representative sites.
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