MGMT (O6 -Methylguanine-DNA Methyltransferase) suppresses tumor development by removing alkyl adduct, while SPOCK2 (SPARC/Osteonectin CWCV and Kazal-like domains proteoglycan) abolishes the inhibition of membrane-type matrix metalloproteinases (MT-MMP) which leads to angiogenesis. Hence, MGMT methylation may initiate malignant cells transformation. In contrast, SPOCK2 methylation is hypothesized not to be a common event in diffuse large B-cell lymphoma (DLBCL). In this study, we examined the methylation status of MGMT and SPOCK2 in DLBCL as in Malaysia the information is extremely lacking. A total of 88 formalin-fixed paraffin-embedded tissue of patients diagnosed with DLBCL from the year 2006 to 2013 were retrieved from Hospital Universiti Sains Malaysia, Kelantan and Hospital Tengku Ampuan Afzan, Pahang. Methylation-specific polymerase chain reaction (MSP) was used to examine the methylation status of both genes. Interestingly, methylation of MGMT was detected in all the 88 DLBCL samples, whereas SPOCK2 was found to be methylated in 83 of 88 (94.3%) DLBCL cases. Our study showed a remarkably high percentage of promoter methylation of both MGMT and SPOCK2 genes. Our finding also negates initial expectation that SPOCK2 methylation would be an uncommon event in the majority of DLBCL cases. This study has shown a very high percentage of promoter methylation of MGMT and SPOCK2 in the DLBCL cases studied by MSP, using archival lymphoma tissues. Nonetheless, additional research is needed to quantitatively evaluate MGMT and SPOCK2 methylation, and to analyse gene expression and/or protein expression in order to further understand the role of MGMT and SPOCK2 methylation in the pathogenesis of DLBCL.

The aim of this work was to develop, optimize and characterize a silymarin-laden polyvinylpyrrolidone (PVP)-polyethylene glycol (PEG) polymeric composite to resolve low aqueous solubility and dissolution rate problem of the drug. A number of silymarin-laden polymeric formulations were fabricated with different quantities of PVP K-30 and PEG 6000 by the solvent-evaporation method. The effect of PVP K-30 and PEG 6000 on the aqueous solubility and dissolution rate was investigated. The optimized formula-tion and its constituents were characterized using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) techniques. Both the PEG 6000 and PVP K-30 positively affected the aqueous solubility and dis-solution rate of the drug. In particular, a formulation consisting of silymarin, PVP K-30 and PEG 6000 (0.25/1.5/1.5, w/w/w) furnished the highest solubility (24.3972.95 mg/mL) and an excellent dissolution profile (～100％ in 40 min). The solubility enhancement with this formulation was ～1150-fold as com-pared to plain silymarin powder. Moreover, all the constituents existed in the amorphous state in this silymarin-laden PVP-PEG polymeric composite. Accordingly, this formulation might be a promising tool to administer silymarin with an enhanced effect via the oral route.

Objective: To evaluate hepatoprotective potential of the methanolic extract of Hedyotis corymbosa against D-galactosamine-induced hepatopathy in experimental animals. Methods: In the present study, in- vivo hepatoprotective effect of 50% methanolic extract of Hedyotis corymbosa (HCE, 100 and 200 mg/kg body weight) was evaluated using experimental models D-Galactosamine (D-GalN) (200 mg/kg, body weight i.p.) induced hepatotoxicity in experimental animals. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), γ-glutamyl transferase (γ-GT) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Results: Obtained results demonstrated that the treatment with HCE signi-cantly (P<0.05-P<0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore, HCE signi-cantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed that HCE attenuated the hepatocellular necrosis and led to reduction of in ammatory cells in-ltration. Conclusions: The results of this study strongly indicate the protective effect of HCE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scienti-cally support its traditional use.