Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions.

BACKGROUND: Complete healing of diabetic wounds continues to be a clinically unmet need. Although robust therapies such as stem cell therapy and growth factor treatment are clinically applied, these treatments are costly for most diabetic wound patients. Therefore, a cheaper alternative is needed. Cobalt protoporphyrin (CoPP) has recently been demonstrated to promote tissue regeneration. In this study, the therapeutic benefits of CoPP in diabetic wound healing were examined. METHODS: An in vitro wound healing model that mimics re-epithelialization was established to examine the effect of CoPP on the migratory capability of human keratinocytes (HaCaT) in either normal glucose (NG) or high glucose (HG) media, as well as in the presence of either H2O2 or lipopolysaccharide (LPS). At the end of the migration assays, cells were collected and subjected to Western blotting analysis and immunostaining. RESULTS: HaCaT were found to migrate significantly more slowly in the HG media compared to the NG media. CoPP treatment was found to enhance cell migration in HG media, but was found to decrease cell migration and proliferation when HaCaT were cultured in NG media. CoPP treatment induced high levels of expression of Nrf-2/HO-1 and FoxO1 in HaCaT cultured in either glucose concentration, although the FoxO1 expression was found to be significantly higher in HaCaT that underwent the migration assay in NG media compared to those in HG media. The higher level of FoxO1 expression seen in CoPP-treated HaCaT cultured in NG media resulted in upregulation of CCL20 and downregulation of TGFß1. In contrast, HaCaT migrated in HG media were found to have high levels of expression of TGFß1, and low levels of expression of CCL20. Interestingly, in the presence of H2O2, CoPP-pretreated HaCaT cultured in either NG or HG media had similar expression level of Nrf-2/HO-1 and FoxO1 to each other. Moreover, the anti-apoptotic effect of CoPP pretreatment was noticed in HaCaT cultured in either glucose concentration. Additionally, CoPP pretreatment was shown to promote tight junction formation in HaCaT suffering from LPS-induced damage. CONCLUSIONS: CoPP enhances cell migratory capacity under hyperglycemic conditions, and protects cells from oxidative and LPS-induced cellular damage in HG media containing either H2O2 or LPS.

Bacterial brain abscess in patients with nasopharyngeal carcinoma following radiotherapy: microbiology, clinical features and therapeutic outcomes.

BACKGROUND: This study aimed to analyze the clinical features, causative pathogens, neuro-imaging findings, and therapeutic outcomes of bacterial brain abscess in patients with nasopharyngeal carcinoma (NPC) following radiotherapy. METHODS: NPC patients with bacterial brain abscess were evaluated. Their clinical data were collected over a 22-year period. For comparison, the clinical features, causative pathogens, neuro-imaging findings, and therapeutic outcomes between NPC and non-NPC patients were analyzed. RESULTS: NPC accounted for 5.7% (12/210) of the predisposing factors, with Viridans streptococci and Staphylococcus aureus as the two most common causative pathogens. Significant statistical analysis between the two groups (NPC and non-NPC patients) included chronic otitis media (COM) as the underlying disease, post-radiation necrosis by neuro-imaging, and the temporal lobe as the most common site of brain abscesses. The fatality rate in patients with and without NPC was 16.7% and 20.7%, respectively. CONCLUSIONS: NPC patients with bacterial brain abscess frequently have COM as the underlying disease. Neuro-imaging often reveals both post-radiation necrosis and the temporal lobe as the most common site of brain abscesses, the diagnosis of which is not always a straightforward process. Radiation necrosis can mimic brain abscess on neuro-imaging and pose significant diagnostic challenges. Early diagnosis and treatment is essential for survival.

PLGA Microspheres Loaded with ß-Cyclodextrin Complexes of Epigallocatechin-3-Gallate for the Anti-Inflammatory Properties in Activated Microglial Cells.

Although epigallocatechin-3-gallate (EG) is well-known as a potent antioxidant and free radical scavenger for neurodegenerative diseases, it still has disadvantages that reduce its treatment effectiveness due to low bioavailability, slow absorption, and water solubility. Therefore, the aim of this study is to improve the bioavailability of EG and increase the effectiveness of anti-inflammatory properties to microglial cells by using Poly(Lactide-co-Glycolide) (PLGA) microspheres as carriers. In this study, we used UV⁻Vis spectroscopy to show the formation of the complex of ß-cyclodextrin (ß-CD) and EG (CD-EG). The loading efficiency of EG in PLGA microspheres was optimized by the addition of ß-CD. The highest loading efficiency of 16.34% was found among other formulations. The results of Fourier transform infrared spectroscopy indicated the loading of CD-EG in PLGA microspheres. The scanning electron microscopic images demonstrated the spherical PLGA particles with controlled particles size ranging from 1⁻14 µm. Moreover, the in vitro release of EG was conducted to explore the sustained release property of the PLGA formulations. In the in vitro model of mouse microglial cells (BV-2 cells) stimulated by lipopolysaccharide, the cytotoxicity test showed that for up to 1 mg/mL of PLGA microspheres no toxicity to BV-2 cells was found. PLGA microspheres can significantly suppress the nitric oxide production from BV-2 cells, indicating EG loaded in PLGA microspheres can suppress the inflammation of activated microglial cells. Furthermore, the intracellular iNOS in BV-2 cells was also found to be down regulated. In summary, we have successfully shown that the use of ß-CD can increase the loading efficiency of EG in PLGA microspheres and provide neuroprotective effect on the activated microglial cells.

Surgical and endovascular treatment for ruptured anterior circulation cerebral aneurysms: a comparison of outcomes--a single centre study from Taiwan.

The purpose of this 2-year retrospective study is to compare the outcomes of patients with either surgical clipping or endovascular coiling treatment for ruptured anterior circulation cerebral aneurysms. We enrolled 100 patients with spontaneous subarachnoid hemorrhage resulting from ruptured anterior circulation cerebral aneurysms. We reviewed the demographic information, operative details, and image examinations including computed tomography (CT), digital subtraction angiography, and magnetic resonance imaging of brains. The patients were subdivided into two groups on the basis of treatment modalities: surgical clipping (N = 44) or endovascular coiling (N = 56). The modified Rankin's scale (mRS) was used as an outcome measures. Unfavorable outcome was defined by a mRS score of 1-3. The mean age of 100 patients, comprising 35 men and 65 women, was 57.48 ± 12.68 years. The follow-up period was 18.91 ± 13.05 months in average. The differences between the clipping and coiling groups in terms of admission Glasgow Coma Scale, Hunt and Hess grade, World Federation of Neurosurgical Societies grade, and Fisher's grade by CT scans were not statistically significant. There was no intergroup difference in the following results: symptomatic or radiographic vasospasm, post-treat rebleeding, and recurrence of aneurysms. Although the incidences of unfavorable outcome at the end of follow-up were 32.0% and 27.0% in the clipping and coiling group respectively, it revealed no significant difference (p = 0.202). In dealing with the patients with ruptured anterior circulation cerebral aneurysms, our results provide helpful information when discussing projected outcome before surgical or endovascular treatment.