Linking Diabetes to Alzheimer's Disease: Potential Roles of Glucose Metabolism and Alpha-Glucosidase.

Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) are more prevalent with ageing and cause a substantial global socio-economic burden. The biology of these two conditions is well elaborated, but whether AD and type 2 DM arise from coincidental roots in ageing or are linked by pathophysiological mechanisms remains unclear. Research findings involving animal models have identified mechanisms shared by both AD and type 2 DM. Deposition of ß-amyloid peptides and formation of intracellular neurofibrillary tangles are pathological hallmarks of AD. Type 2 DM, on the other hand, is a metabolic disorder characterised by hyperglycaemia and insulin resistance. Several studies show that improving type 2 DM can delay or prevent the development of AD, and hence, prevention and control of type 2 DM may reduce the risk of AD later in life. Alpha-glucosidase is an enzyme that is commonly associated with hyperglycaemia in type 2 DM. However, it is uncertain if this enzyme may play a role in the progression of AD. This review explores the experimental evidence that depicts the relationship between dysregulation of glucose metabolism and AD. We also delineate the links between alpha-glucosidase and AD and the potential role of alpha-glucosidase inhibitors in treating AD.

TGF-ß1 and -ß3 for Mesenchymal Stem Cells Chondrogenic Differentiation on Poly (Vinyl Alcohol)-Chitosan-Poly (Ethylene Glycol) Scaffold.

Transforming growth factor-beta 1 (TGF-ß1) has been reported to promote chondrogenic differentiation and proliferation in the multipotent stromal cell (MSCs), and the transforming growth factor-beta 3 (TGF-ß3) tends to be exclusively in promoting cell differentiation alone. The objective of this study was to determine the effect of TGF-ß1 and -ß3 on the MSCs chondrogenic differentiation on the poly (vinyl alcohol)-chitosan-poly (ethylene glycol) (PVA-NOCC-PEG) scaffold, compared with that of monolayer and pellet cultures. In this study, P2 rabbit bone marrow-derived MSCs were seeded either on the untreated six-well plate (for monolayer culture) or onto the PVA-NOCC-PEG scaffold or cultured as a pellet culture. The cultures were maintained in a chemically defined serum-free medium supplemented with 10 ng/mL of either TGF-ß1 or TGF-ß3. Cell viability assay, biochemical assay, and real-time polymerase chain reaction were performed to determine the net effect of cell proliferation and chondrogenic differentiation of each of the growth factors. The results showed that the PVA-NOCC-PEG scaffold enhanced MSCs cell proliferation from day 12 to 30 (p < 0.05); however, no significant differences were observed in the cell proliferation between the cultures supplemented with or without TGF-ß1 and TGF-ß3 (p > 0.05). In terms of chondrogenic differentiation, the PVA-NOCC-PEG scaffold augmented the GAGs secretion in MSCs and the mRNA expression levels of Sox9, Col2a1, Acan, and Comp were elevated (p < 0.05). However, there was no significant difference between both the TGF-ß1 and TGF-ß3-treated groups (p > 0.05). In conclusion, TGF-ß1 and TGF-ß3 enhanced the chondrogenic differentiation of MSCs seeded on the PVA-NOCC-PEG scaffold; however, there was no significant difference between the effect of TGF-ß1 and TGF-ß3. Impact statement Transforming growth factor-beta (TGF-ß) superfamily members is a key requirement for the in vitro chondrogenic differentiation of mesenchymal stem cells (MSCs). In this study, the effects of TGF-ß1 and -ß3 on MSC chondrogenic differentiation and proliferation on a novel three-dimensional scaffold, the poly(vinyl alcohol)-chitosan-poly(ethylene glycol) (PVA-NOCC-PEG) scaffold, was evaluated. In this study, the results showed both TGF-ß1 and TGF-ß3 can enhance the chondrogenic differentiation of MSCs seeded on the PVA-NOCC-PEG scaffold.

Total cell pooling in vitro: an effective isolation method for bone marrow-derived multipotent stromal cells.

In vitro cellular proliferation and the ability to undergo multilineage differentiation make bone marrow-derived multipotent stromal cells (MSCs) potentially useful for clinical applications. Several methods have been described to isolate a homogenous bone marrow-derived MSCs population; however, none has been proven most effective, mainly due to their effects on proliferation and differentiation capability of the isolated cells. It is hypothesized that our newly established total cell pooling method may provide a better alternative as compared to the standard isolation method (density gradient centrifugation method). For the total cell pooling method, MSCs were isolated from rabbit bone marrow and were subsequently cultured in the growth medium without further separation as in the standard isolation method. The total cell pooling method was 65 min faster than the standard isolation method in completing cell isolation. Nevertheless, both methods did not differ significantly in the number of primary viable cells and population doubling time in the cultures (p > 0.05). The isolated cells from both methods expressed CD29 and CD44 markers, but not CD45 markers. Furthermore, they displayed multilineage differentiation characteristics of chondroblasts, osteoblasts, and adipocytes. In conclusion, both methods provide similar efficiency in the isolation of rabbit bone marrow-derived MSCs; however, the total cell pooling method is technically simpler and more cost effective than the standard isolation method.

Adult anthropometric measures and socio-demographic factors influencing age at menarche of university students in malaysia.

Early onset of menarche has been shown to be associated with breast cancer and ischaemic heart disease. Studies on age at menarche of the Malaysian population are poorly documented. This study aimed to determine the influence of anthropometric and socio-demographic factors on the age at menarche of university students in Malaysia. Data were obtained in 2010-11 from 961 students between the ages of 18 and 25 years from the University of Malaya using stratified sampling, and multiple regression analysis was applied. Sixty-three per cent of students reached menarche at the age of 12 or 13 years, with the mean and median of age at menarche being 12.45 ± 1.17 and 12.01 years, respectively. Menarcheal age was positively associated with height (p<0.05) and negatively associated with BMI (p<0.001). Students from urban areas attained menarche earlier than those from rural areas (p<0.05). Students from small-sized families attained menarche earlier than those from larger families (p<0.05). First-born students experienced menarche earlier than those who were seventh-born or later. Obese and overweight students reached menarche earlier than students who were underweight or of normal weight (p<0.01). The variations in age at menarche among the Malaysian ethnic groups were statistically insignificant. The results suggest that heavier and first-born students from small families are more likely to attain menarche earlier than their counterparts.

Supermacroporous poly(vinyl alcohol)-carboxylmethyl chitosan-poly(ethylene glycol) scaffold: an in vitro and in vivo pre-assessments for cartilage tissue engineering.

This study aims to pre-assess the in vitro and in vivo biocompatibility of poly(vinyl alcohol)-carboxylmethyl-chitosan-poly(ethylene glycol) (PCP) scaffold. PCP was lyophilised to create supermacroporous structures. 3-(4, 5-dimethyl-thiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and immunohistochemistry (IHC) were used to evaluate the effectiveness of PCP scaffolds for chondrocytes attachment and proliferation. The ultrastructural was assessed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Extracellular matrix (ECM) formation was evaluated using collagen type-II staining, glycosaminoglycan (GAG) and collagen assays. Histological analysis was conducted on 3-week implanted Sprague-Dawley rats. The MTT, IHC, SEM and TEM analyses confirm that PCP scaffolds promoted cell attachment and proliferation in vitro. The chondrocyte-PCP constructs secreted GAG and collagen type-II, both increased significantly from day-14 to day-28 (P < 0.05). PCP scaffolds did not elicit any adverse effects on the host tissue, but were partially degraded. These results suggest that supermacroporous PCP is a biocompatible scaffold for clinical applications.