HnRNPL inhibits the osteogenic differentiation of PDLCs stimulated by SrCl2 through repressing Setd2

Osteoporosis has been shown to intensify bone loss caused by periodontitis and both share common risk factors. One strategy utilized to manage the disease has been via the release of Sr ions by Strontium Ranelate having a direct effect on preventing osteoclast activation and promoting osteoblast differentiation. Previously we have developed and characterized porous Sr‐mesoporous bioactive glass (Sr‐MBG) scaffolds and demonstrated their ability to promote periodontal regeneration when compared to MBG alone. Our group further discovered a splicing factor, heterogeneous nuclear ribonucleoprotein L (hnRNPL), was drastically down‐regulated in periodontal ligament stem cells (PDLCs) stimulated by Sr through the activation of AKT pathway. Furthermore, hnRNPL restrained the osteogenic differentiation of PDLCs through down‐regulating H3K36me3‐specific methyltransferase Setd2. The goal of the present study was to investigate the mechanism of periodontal regeneration stimulated by Sr It was first found that the epigenetic mechanism of splicing factor hnRNPL participated in the osteogenesis processing of PDLCs stimulated by SrCl₂. Meanwhile, the different role of hnRNPL and SET domain containing 2 (Setd2) may provide some implication of the treatment of periodontitis patients simultaneously suffering from osteoporosis.     

An overview of the two-phase solvent systems used in the countercurrent separation of phenylethanoid glycosides and iridoids and their biological relevance

Phytochemistry Reviews - Phenylethanoid glycosides (PhGs) and iridoids are two vast groups of water soluble secondary metabolites widely distributed in plant kingdom and well known for their...     

Assessment of Choroidal Thickness in Healthy and Glaucomatous Eyes Using Swept Source Optical Coherence Tomography

Purpose

To evaluate choroidal thickness (CT) in healthy and glaucomatous eyes using Swept Source Optical Coherence Tomography (SS-OCT).

Methods

A cross-sectional observational study of 216 eyes of 140 subjects with glaucoma and 106 eyes of 67 healthy subjects enrolled in the Diagnostic Innovations in Glaucoma Study. CT was assessed from wide-field (12×9 mm) SS-OCT scans. The association between CT and potential confounding variables including age, gender, axial length, intraocular pressure, central corneal thickness and ocular perfusion pressure was examined using univariable and multivariable regression analyses.

Results

Overall CT was thinner in glaucomatous eyes with a mean (± standard deviation) of 157.7±48.5 µm in glaucoma compared to 179.9±36.1 µm in healthy eyes (P<0.001). The choroid was thinner in both the peripapillary and macular regions in glaucoma compared to controls. Mean peripapillary CT was 154.1±44.1 µm and 134.0±56.9 µm (P<0.001) and macular CT 199.3±46.1 µm and 176.2±57.5 µm (P<0.001) for healthy and glaucomatous eyes respectively. However, older age (P<0.001) and longer axial length (P<0.001) were also associated with thinner choroid and when differences in age and axial length between glaucomatous and healthy subjects were accounted for, glaucoma was not significantly associated with CT. There was also no association between glaucoma severity and CT.

Conclusions

Glaucoma was not associated with CT measured using SS-OCT; however, older age and longer axial length were associated with thinner choroid so should be considered when interpreting CT measurements.     

Glaucomatous Patterns in Frequency Doubling Technology (FDT) Perimetry Data Identified by Unsupervised Machine Learning Classifiers

Purpose

The variational Bayesian independent component analysis-mixture model (VIM), an unsupervised machine-learning classifier, was used to automatically separate Matrix Frequency Doubling Technology (FDT) perimetry data into clusters of healthy and glaucomatous eyes, and to identify axes representing statistically independent patterns of defect in the glaucoma clusters.

Methods

FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal FDT results from the UCSD-based Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). For all eyes, VIM input was 52 threshold test points from the 24-2 test pattern, plus age.

Results

FDT mean deviation was −1.00 dB (S.D. = 2.80 dB) and −5.57 dB (S.D. = 5.09 dB) in FDT-normal eyes and FDT-abnormal eyes, respectively (p<0.001). VIM identified meaningful clusters of FDT data and positioned a set of statistically independent axes through the mean of each cluster. The optimal VIM model separated the FDT fields into 3 clusters. Cluster N contained primarily normal fields (1109/1190, specificity 93.1%) and clusters G₁ and G₂ combined, contained primarily abnormal fields (651/786, sensitivity 82.8%). For clusters G₁ and G₂ the optimal number of axes were 2 and 5, respectively. Patterns automatically generated along axes within the glaucoma clusters were similar to those known to be indicative of glaucoma. Fields located farther from the normal mean on each glaucoma axis showed increasing field defect severity.

Conclusions

VIM successfully separated FDT fields from healthy and glaucoma eyes without a priori information about class membership, and identified familiar glaucomatous patterns of loss.     

Osteogenic Properties of PBLG-g-HA/PLLA Nanocomposites

New development of biomaterial scaffolds remains a prominent issue for the regeneration of lost or fractured bone. Of these scaffolds, a number of bioactive polymers have been synthesized and fabricated for diverse biological roles. Although recent evidence has demonstrated that composite scaffolds such as HA/PLLA have improved properties when compared to either HA or PLLA alone, recent investigations have demonstrated that the phase compatibility between HA and PLLA layers is weak preventing optimal enhancement of the mechanical properties and making the composites prone to breakdown. In the present study, poly (γ-benzyl-L-glutamate) modified hydroxyapatite/(poly (L-lactic acid)) (PBLG-g-HA/PLLA) composite scaffolds were fabricated with improved phase compatibility and tested for their osteogenic properties in 18 Wistar female rats by analyzing new bone formation in 3 mm bilateral femur defects in vivo. At time points, 2, 4 and 8 weeks post surgery, bone formation was evaluated by µ-CT and histological analysis by comparing 4 treatment groups; 1) blank defect, 2) PLLA, 3) HA/PLLA and 4) PBLG-g-HA/PLLA scaffolds. The in vivo analysis demonstrated that new bone formation was much more prominent in HA/PLLA and PBLG-g-HA/PLLA groups as depicted by µ-CT, H&E staining and immunohistochemistry for collagen I. TRAP staining was also utilized to determine the influence of osteoclast cell number and staining intensity to the various scaffolds. No significant differences in either staining intensity or osteoclast numbers between all treatment modalities was observed, however blank defects did contain a higher number of osteoclast-like cells. The results from the present study illustrate the potential of PBLG-g-HA/PLLA scaffolds for bone tissue engineering applications by demonstrating favorable osteogenic properties.     

Molecular interactions between Wells-Dawson type polyoxometalates and human serum albumin

Binding human serum albumin (HSA) of three polyoxometalates (POMs) with the Wells-Dawson structure, alpha(2)-[P2W17O61]10- (abbreviated as alpha(2)-P2W17) and two of its metal-substituted derivatives, alpha(2)-[NiP2W17O61]8- and alpha(2)-[CuP2W17O61]8- (alpha(2)-P2W17Ni and alpha(2)-P2W17Cu, respectively) was studied in an aqueous medium at pH 7.5. Fluorescence quenching, circular dichroism (CD), thermal denaturation, and isothermal titration calorimetry (ITC) were used for this purpose. The results were compared with those obtained previously with the Keggin structure POM, [H2W12O40]6- (H2W12), and the wheel-shaped structure, [NaP5W30O110]14- (P5W30). All these POMs bind HSA mainly by electrostatic interactions. Comparison of the physical characteristics and HSA interaction parameters for the POMs of the present work and those studied previously showed that the overall charge of the clusters is not the single parameter governing the binding process and its consequences. In contrast, besides the influences of the structure, the dimension and/or weight of the POMs, the results have permitted highlighting of the importance of each POM atomic composition for its binding behavior.     

Predation on soft-shell clams (Mya arenaria) by the nemertean Cerebratulus lacteus in Atlantic Canada: implications for control measures

The nemertean, Cerebratulus lacteus Verrill (Nemertinea: Heteronemertini), has been identified as an important threat to soft-shell clam (Mya arenariaL.) populations in Atlantic Canada. The biology of this species, however, is still largely unknown. Field and laboratory studies were undertaken in 1998 and 1999 in Prince Edward Island, Canada, to test certain control measures to reduce predation on soft-shell clam populations and to better describe the relationship between C. lacteus and M. arenaria. Field abundance of C. lacteus, M. arenaria and Nereis virens Sars were evaluated in relation to particular habitat modifications that were used as control measures. Sediment manipulations tested were: (1) addition of shells and (2) use of a hydraulic rake. No difference was observed on the abundance of C. lacteus, M. arenaria and N. virens after treatments were applied. In the laboratory, C. lacteus was shown to be an efficient predator of M. arenaria. Clam mortalities reached 100% in the presence of C. lacteus while 0% mortality was observed in its absence. A complementary set of experiments was carried out to see if the sympatric polychaetes N. virens and Glycera dibranchiata Ehlers had any impact on the relationship between C. lacteus and M. arenaria. N. virens showed no impact on C. lacteus predation on clams. The presence of G. dibranchiata significantly reduced the nemertean predation rate. Analysis of clam size selection revealed no significant preference by C. lacteus. Other experimental studies revealed that high predator densities did not impede predation on clams and that C. lacteus preferred soft-shell clams among other commercial bivalve species presented (Mercenaria mercenariaL., Crassostrea virginica Gmelin and Mytilus edulisL.). This study should provide a better understanding of the relationship between C. lacteus and M. arenaria and lead to the development of improved nemertean control measures.