Ocular and Hemodynamic Factors Contributing to the Central Visual Function in Glaucoma Patients With Myopia.

Purpose: The purpose of this study was to investigate the ocular and hemodynamic factors contributing to the central visual function in glaucoma patients with myopia. Methods: This study was a prospective observational study, which included 236 eyes of 140 patients with normal-tension glaucoma (NTG), which includes 114 eyes with mild myopia (axial length ≥24 and <26 mm) and 122 eyes with moderate-to-severe myopia (axial length ≥26 mm). Ocular characteristics were axial length and posterior pole profiles, including peripapillary atrophy (PPA) to disc area ratio, disc tilt ratio, disc torsion, and disc-foveal angle. Hemodynamic factors included standard deviation of the mean of qualified normal-to-normal intervals (SDNN) of a heart rate variability (HRV) test and vessel density (VD) parameters from optical coherence tomography angiography (OCTA). The root mean square error was estimated as a measure of the VD fluctuation. Association between ocular characteristics and VD parameters of the OCTA with the central sensitivity of the 10-degree visual field or the presence of central scotoma were analyzed. Results: Deep layer VD of the peripapillary and macular areas showed significant differences between mild and moderate-to-severe myopia (P = 0.034 and P = 0.045, respectively). Structural parameters, especially PPA to disc area ratio, had significant correlation with peripapillary VD parameters in myopic eyes. Lower SDNN value (ß = 0.924, P = 0.011), lower deep VD of the macular area (ß = 0.845, P = 0.001), and greater fluctuation of deep VD in the peripapillary area (ß = 1.517, P = 0.005) were associated with the presence of central scotoma in patients with glaucoma with myopia in multivariate logistic regression analysis. Conclusions: The structural changes by myopia, especially in the peripapillary region, affected VD parameters in myopic eyes. Lower deep VD and greater VD fluctuation in the peripapillary region showed association with central scotoma in patients with glaucoma with myopia, suggesting both structural and vascular changes by myopia may be related to central visual function in glaucoma patients with myopia.

Can glycine betaine denature proteins?

Glycine betaine (GB) is a naturally occurring osmolyte that has been widely recognized as a protein protectant. Since GB consists of a methylated ammonium moiety, it can engage in strong cation-π interactions with aromatic amino acid sidechains. We hypothesize that such specific binding interactions would allow GB to decrease the stability of proteins that are predominantly stabilized by a cluster of aromatic amino acids. To test this hypothesis, we investigate the effect of GB on the stability of two ß-hairpins (or mini-proteins) that contain such a cluster. We find that for both systems the stability of the folded state first decreases and then increases with increasing GB concentration. Such non-monotonic dependence not only confirms that GB can act as a protein denaturant, but also underscores the complex interplay between GB's stabilizing and destabilizing forces toward a given protein. While stabilizing osmolytes all have the tendency to be excluded from the protein surface which is the action underlying their stabilizing effect, our results suggest that in order to quantitatively assess the effect of GB on the stability of any given protein, specific cation-π binding interactions need to be explicitly considered. Moreover, our results show, consistent with other studies, that cation methylation can strengthen the respective cation-π interactions. Taken together, these findings provide new insight into the mechanism by which amino acid-based osmolytes interact with proteins.

Association of Retinal Blood Flow with Progression of Visual Field in Glaucoma.

In the glaucoma clinic, patients with normal intraocular pressure (IOP) can sometimes show visual field (VF) progression. Therefore, clarification of relationship between vascular status and glaucomatous VF deterioration is a focus of interest. We used optical coherence tomography angiography (OCTA), with the aim of evaluating the relationship between vessel density (VD) and VF progression in glaucoma patients. We included 104 eyes with open angle glaucoma who were followed up for at least 5 years in this retrospective case-control study. Superficial and deep VD of macula were assessed by OCTA. Regression analysis and Cox proportional hazards model were used to identify factors significantly associated with VF progression. In logistic regression analysis determining VF progression from Guided Progression Analysis (GPA) program, initial IOP and deep macular VD were significantly associated with VF progression in multivariate analysis (P = 0.019 and 0.004). Cox proportional hazards model also identified deep macular VD as significantly related to VF progression (P = 0.035). In conclusion, initial IOP and deep VD were related to VF deterioration in glaucoma. Deep VD might be used as a surrogate of glaucomatous VF progression related with vascular incompetence.

Marine spongean polybrominated diphenyl ethers, selective growth inhibitors against the cancer cells adapted to glucose starvation, inhibits mitochondrial complex II.

In the course of search for selective growth inhibitors against the cancer cells adapted to nutrient starvation, two polybrominated diphenyl ethers, 3,4,5-tribromo-2-(2',4'-dibromophenoxy)-phenol (1) and 3,5-dibromo-2-(2',4'-dibromophenoxy)-phenol (2) were isolated from an Indonesian marine sponge of Dysidea sp. Compounds 1 and 2 showed the anti-proliferative activity against PANC-1 cells under glucose-starved conditions with IC50 values of 2.1 and 3.8 µM, respectively, whereas no growth inhibition was observed up to 30 µM in the general culture conditions. The further mechanistic analysis indicated that compound 1 might act mainly by inhibiting complex II in the mitochondrial electron transport chain.

N-Methylniphatyne A, a New 3-Alkylpyridine Alkaloid as an Inhibitor of the Cancer Cells Adapted to Nutrient Starvation, from an Indonesian Marine Sponge of Xestospongia sp.

In the course of searching for selective growth inhibitors of the cancer cells adapted to nutrient starvation, a new 3-alkylpyridine alkaloid named N-methylniphatyne A (1) was isolated from an Indonesian marine sponge of Xestospongia sp. The chemical structure of 1 was determined on the basis of the spectroscopic analysis and comparison with the synthesized 1 and its analogues. Compound 1 showed the cytotoxic activity against PANC-1 cells under the condition of glucose starvation with IC50 value of 16 µM, whereas no growth-inhibition was observed up to 100 µM under the general culture conditions.

The serine protease prostasin (PRSS8) is a potential biomarker for early detection of ovarian cancer.

BACKGROUND: Ovarian cancer (OVC) is the deadliest of all gynecologic cancers, primarily as a consequence of asymptomatic progression. The complex nature of OVC creates challenges for early detection, and there is a lack of specific and sensitive biomarkers suitable for screening and detecting early stage OVC. METHODS: Potential OVC biomarkers were identified by bioinformatic analysis. Candidates were further screened for differential expression in a library of OVC cell lines. OVC-specific overexpression of a candidate gene, PRSS8, which encodes prostasin, was confirmed against 18 major human cancer types from 390 cancer samples by qRT-PCR. PRSS8 expression profiles stratified by OVC tumor stage-, grade- and subtype were generated using cDNA samples from 159 OVC samples. Cell-specific expression and localization of prostasin was determined by immunohistological tissue array analysis of more than 500 normal, benign, and cancerous ovarian tissues. The presence of prostasin in normal, benign, and OVC serum samples was also determined. RESULTS: Gene expression analysis indicated that PRSS8 was expressed in OVC at levels more than 100 fold greater than found in normal or benign ovarian lesions. This overexpression signature was found in early stages of OVC and was maintained in higher stages and grades of OVC. The PRSS8 overexpression signature was specific for OVC and urinary bladder cancer among 18 human cancer types. The majority of ovarian cell lines overexpressed PRSS8. In situ hybridization and histopathology studies of OVC tissues indicated that overexpression of prostasin was largely localized to tumor epithelium and was absent in neighboring stroma. Significantly higher levels of prostasin were found in early stage OVC serum samples compared to benign ovarian and normal donor samples. CONCLUSIONS: The abundant amounts of secreted prostasin found in sera of early stage OVC can potentially be used as a minimally invasive screening biomarker for early stage OVC. Overexpression of PRSS8 mRNA and high levels of prostasin in multiple subtypes of early stage ovarian tumors may provide clinical biomarkers for early detection of OVC, which can potentially be used with CA125 and HE4.

Anti-dormant mycobacterial activity and target analysis of nybomycin produced by a marine-derived Streptomyces sp.

In the course of our search for anti-dormant Mycobacterial substances, nybomycin (1) was re-discovered from the culture broth of a marine-derived Streptomyces sp. on the bioassay-guided separation. Compound 1 showed anti-microbial activity against Mycobacterium smegmatis and Mycobacterium bovis BCG with the MIC of 1.0µg/mL under both actively growing aerobic conditions and dormancy inducing hypoxic conditions. Compound 1 is also effective to Mycobacterium tuberculosis including the clinically isolated strains. The mechanistic analysis indicated that 1 bound to DNA and induces a unique morphological change to mycobacterial bacilli leading the bacterial cell death.