Kawasaki disease does not affect coronaries alone: large vessels can be involved as well

Clinical Rheumatology -     

Destabilization of amyloid fibrils on interaction with MoS2-based nanomaterials

The present work is motivated by the established concept that the structure and energetics of biomacromolecules can be modulated by confining their dimensions in the nanoscale. In particular, here we use force-field methods to understand the stability of amyloid fibrils at nanostructured interfaces, which can be useful for the development of new therapeutics for Alzheimer''s disease. We explore the binding modes and structural properties of fibrils at the interface of molybdenum disulphide nanotubes and the nanosurface using classical molecular dynamics simulations. We find that in general the MoS₂ materials induces disruptions in the structure of the amyloid fibrils where the beta sheet conformation of the fibrils changes to a turned conformation, and it is large in the case of nanotubes in comparison to the nanosurfaces. The intermolecular hydrogen bonds, hydrophilic and hydrophobic contacts between the monomer peptides in the fibril are reduced due to their adsorption onto the MoS₂ materials, which results in a destabilization of the fibril. The destabilization of fibril is to some extent compensated for by the van der Waals interactions between the fibril and MoS₂. Overall the results indicate that MoS₂-based materials can be useful in inhibiting the aggregation of smaller protofibrils to matured fibrils and to bust the already formed fibrils. Therapeutic materials should not exhibit any cross interaction with other off-targets compounds. In order to test whether the MoS₂ nanomaterial has any such effect we have studied its interaction with two additional biomacromolecules, the human serum albumin and p53 protein, and we report no significant changes in the secondary structure of these biomolecules. Through molecular docking studies we also established that the drug binding ability of HSA is not altered by its surface binding to MoS₂ nanosurface.

The present work computationally establishes that the structure and energetics of fibril-like biomacromolecules can be modulated by confining them on the MoS₂ based nanomaterials.     

Antihyperlipidemic effect of curcumin and tetrahydrocurcumin in experimental type 2 diabetic rats

Hyperlipidemia is an associated complication of diabetes mellitus. In the present study, we investigated the effect of tetrahydrocurcumin (THC), one of the active metabolites of curcumin on lipid profile in streptozotocin (STZ)-nicotinamide-induced diabetic rats. THC 80 mg/kg body weight was orally administered to diabetic rats for 45 days, resulting in a significant reduction in blood glucose and a significant increase in plasma insulin in diabetic rats, which proved that THC possess an antidiabetic effect. THC also caused a significant reduction serum and liver cholesterol, triglycerides, free fatty acids, phospholipids, HMG CoA reductase activity, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol levels. The decreased serum high-density lipoprotein (HDL) cholesterol in diabetic rats was also reversed toward normalization after the treatment. These biochemical observations were supplemented by histopathological examination of liver section. The effect was compared with curcumin (80 mg/kg body weight). The results showed that THC had antihyperlipidemic action in control and experimental diabetic rats. The antidiabetic and antihyperlipidemic effects of THC are more potent than those of curcumin at the same dose.     

Production of ultra-fine bioresorbable carbonated hydroxyapatite

Ionic-substituted hydroxyapatite (HAp) based materials may be a better choice than pure HAp owing to their similarity in chemical composition with biological apatite. The present study reports a process for the production of carbonated hydroxyapatite (CHAp) using microwaves. The CHAp was evaluated for its phase purity, chemical homogeneity, functionality, morphology, and solubility. The CHAp thus obtained was compared with a pure HAp and a biological apatite, which provides quite an interesting insight into the carbonate substitution. The in vitro ionic dissolution rates determined under physiological conditions clearly demonstrate the soluble nature of CHAp compared to HAp. The overall results indicate that the processed CHAp has increased resorption relative to pure HAp and has a chemical composition corresponding to some extent with that of biological apatite.     

The role of DCX and LIS1 in migration through the lateral cortical stream of developing forebrain

During forebrain development the lateral cortical stream (LCS) supplies neurons to structures in the ventral telencephalon including the amygdala and piriform cortex. In the current study, we used spatially directed in utero electroporation and RNAi to investigate mechanisms of migration to the ventral telencephalon. Cells labeled by in utero electroporation of the lateral ventricular zone migrated into the LCS, and entered the lateral neocortex, piriform cortex and amygdala, where they differentiated primarily as pyramidal neurons. RNAi of DCX or LIS1 disrupted migration into amygdala and piriform cortex and caused many neurons to accumulate in the external and amygdalar capsules. RNAi of LIS1 and DCX had similar as well as distinguishable effects on the pattern of altered migration. Combinatorial RNAi of LIS1 and DCX further suggested interaction in the functions of LIS1 and DCX on the morphology and migration of migrating neurons in the LCS. Together, these results confirm that the LCS contributes pyramidal neurons to ventral forebrain structures and reveals that DCX and LIS1 have important functions in this major migratory pathway in the developing forebrain.     

Prevalence of oral submucous fibrosis among areca nut chewers: A systematic review and meta-analysis

Background: Worldwide millions peoples consume AN who are at risk of OSMF. Prevalence of OSMF is reported between 0.03% and 30% irrespective of AN habit. Further, these estimates are based on sample population comprised of OSMF patients or general population rather AN chewers (ANC). Therefore, available evidence does not reflect the true prevalence of OSMF among ANC. Method: The studies providing the prevalence of OSMF in ANC were identified in PubMed, Scopus, and Web of Science. Pooled prevalence and quality assessment using New-Ottawa Scale were performed. Results: Fifteen studies reported the prevalence of OSMF (929) in ANC (53,213). Most studies were from China (six studies) and India (four studies) correlating with regions having high ANC. The pooled prevalence of OSMF in ANC was 5% (0.05 [95% CI, 0.03, 0.08]). All studies' quality was satisfactory; however, the OSMF diagnosis method, age, gender, and habits need further scrutiny. Conclusion: Available evidence suggested a low prevalence of OSMF in ANC, although further large-scale studies are recommended to validate this finding. Understanding the prevalence and distribution patterns of OSMF might aid intervention healthcare programs and contribute to the reduction of the oral cancer burden related to OSMF.     

Purification of human adipose-derived stem cells from fat tissues using PLGA/silk screen hybrid membranes

The purification of human adipose-derived stem cells (hADSCs) from human adipose tissue cells (stromal vascular fraction) was investigated using membrane filtration through poly(lactide-co-glycolic acid)/silk screen hybrid membranes. Membrane filtration methods are attractive in regenerative medicine because they reduce the time required to purify hADSCs (i.e., less than 30 min) compared with conventional culture methods, which require 5–12 days. hADSCs expressing the mesenchymal stem cell markers CD44, CD73, and CD90 were concentrated in the permeation solution from the hybrid membranes. Expression of the surface markers CD44, CD73, and CD99 on the cells in the permeation solution from the hybrid membranes, which were obtained using 18 mL of feed solution containing 50 × 10⁴ cells, was statistically significantly higher than that of the primary adipose tissue cells, indicating that the hADSCs can be purified in the permeation solution by the membrane filtration method. Cells expressing the stem cell-associated marker CD34 could be successfully isolated in the permeation solution, whereas CD34⁺ cells could not be purified by the conventional culture method. The hADSCs in the permeation solution demonstrated a superior capacity for osteogenic differentiation based on their alkali phosphatase activity, their osterix gene expression, and the results of mineralization analysis by Alizarin Red S and von Kossa staining compared with the cells from the suspension of human adipose tissue. These results suggest that the hADSCs capable of osteogenic differentiation preferentially permeate through the hybrid membranes.