Synergistic effects of cisplatin and apigenin on telomerase expression and telomerase activity in TNBC cells / Associate Professor Dr Gabriele Ruth Anisah Froemming and Noorfaiza A.Aziz

Triple Negative Breast Cancer (TNBC) is highly heterogeneous and metastatic breast cancer form with a low five-year survival rate diagnosed patients. As TNBC is negative for the expression of estrogen (ER), progesterone (PR) and Her2neu receptors it has limited treatment options due to a lack of molecular targets and the heterogeneity of deregulated pathways

Fatty acids composition and antimicrobial activities of Litsea garciae pulp and seed extracts

Litsea garciae is a native plant to Borneo Island. The current study aimed to identify and compare the fatty acids composition and antimicrobial activities of the pulp and seed extracts of L. garciae. The total lipids of L. garciae pulp and seed were extracted with petroleum ether (PE) and Bligh-Dyer (BD) methods and the fatty acids were analysed using gas chromatography. The fatty acids of seed extracts consisted of more than 80% saturated fatty acids whereas the pulp extracts contained a similar percentage of saturated and unsaturated fatty acids (approximately 50%). The predominant saturated fatty acids were palmitic acid followed by stearic acid for both PE and BD lipid pulp extracts. In contrast, the PE and BD lipid seed extracts had a high content of lauric acid followed by palmitic acid. The predominant monounsaturated fatty acid was oleic acid while polyunsaturated fatty acid was linoleic acid for all extracts. As for the antimicrobial activities, PE lipid pulp extract had higher antimicrobial activity against S. aureus, P. aeruginosa, and S. epidermidis than other extracts in both antimicrobial assays. This study showed that the PE and BD lipid pulp and seed extracts had similar major components of fatty acids but with different proportions. In addition, the components of fatty acids might contribute to the antibacterial activities of L. garciae

Inflammation and Vascular Calcification Causing Effects of Oxidized HDL are Attenuated by Adiponectin in Human Vascular Smooth Muscle Cells

The role of oxidized high- density lipoprotein (oxHDL) and the protective effects of adiponectin in terms of vascular calcification is not well-established. This study was conducted to investigate the effects of oxHDL with regard to inflammation and vascular calcification and to determine the protective role of adiponectin in attenuating the detrimental effects of oxHDL. Cell viability, mineralization, and calcification assays were conducted to optimize the concentration of oxHDL. Then, human vascular smooth muscle cells (HAoVSMCs) were incubated with β-glycerophosphate, HDL, oxHDL, adiponectin, or the combination of oxHDL with adiponectin for 24 h. Protein expression of IL-6, TNF-α, osterix, RUNX2, ALP, type 1 collagen, osteopontin, osteocalcin, WNT-5a, NF-ĸβ(p65), cAMP and STAT-3 were measured by ELISA kits. OxHDL induced vascular calcification by promoting the formation of mineralization nodules and calcium deposits in HAoVSMCs. This was accompanied by an increased secretion of IL-6, osterix, WNT-5a and NF-ĸβ (p65). Interestingly, these detrimental effects of oxHDL were suppressed by adiponectin. Besides, incubation of adiponectin alone on HAoVSMCs showed a reduction of inflammatory cytokines, osteoblastic markers (RUNX2, osterix and osteopontin), WNT-5a and NF-ĸβ (p65). This study exhibits the ability of oxHDL in inducing inflammation and vascular calcification and these detrimental effects of oxHDL can be attenuated by adiponectin

HDL and its subpopulation (HDL2 AND HDL3) promote cholesterol transporters expression and attenuate inflammation in 3t3-l1 mature adipocytes induced by tumor necrosis factor-alpha

Obesity activates inflammation causing dysfunction of adipocytes. Increasing high-density lipoprotein (HDL) levels in obesity may be beneficial in overcoming this effect. However, not much data is available on the effects of HDL and its subpopulations in inflamed adipocytes. The objective of this study was to investigate the effects of total HDL (tHDL) and the comparison between its subpopulations (HDL2 & HDL3) on protein and gene expression of cholesterol transporters, inflammation, and adipokines in TNF-α stimulated 3T3-L1 mature adipocytes. TNFα alone had lower adiponectin and higher protein and gene expression of IL-6 and NF-ĸβ (p65) compared to unstimulated adipocytes and these effects were attenuated by HDLs especially HDL3 (in most of the biomarkers). HDL and its subpopulation had higher cholesterol transporters expression in 3T3-L1 mature adipocytes induced by TNF-α compared to unstimulated cells. Increment of cholesterol transporters expression by HDL leads to reduce secretion of inflammatory markers [IL-6 & NF-kB (p65)] and visfatin and increases adiponectin secretion in the inflamed mature adipocytes. HDL exhibits beyond its reverse cholesterol transporter property by exhibiting anti-inflammatory effects thru the deactivation of NF-ĸβ (p65). This may contribute to reducing the progression of obesity-related complications

HDL and its subpopulation (HDL2 and HDL3) promote cholesterol transporters expression and attenuate inflammation in 3T3-L1 mature adipocytes induced by tumor necrosis factor-alpha

Obesity activates inflammation causing dysfunction of adipocytes. Increasing high-density lipoprotein (HDL) levels in obesity may be beneficial in overcoming this effect. However, not much data is available on the effects of HDL and its subpopulations in inflamed adipocytes. The objective of this study was to investigate the effects of total HDL (tHDL) and the comparison between its subpopulations (HDL2 & HDL3) on protein and gene expression of cholesterol transporters, inflammation, and adipokines in TNF-α stimulated 3T3-L1 mature adipocytes. TNFα alone had lower adiponectin and higher protein and gene expression of IL-6 and NF-ĸβ (p65) compared to unstimulated adipocytes and these effects were attenuated by HDLs especially HDL3 (in most of the biomarkers). HDL and its subpopulation had higher cholesterol transporters expression in 3T3-L1 mature adipocytes induced by TNF-α compared to unstimulated cells. Increment of cholesterol transporters expression by HDL leads to reduce secretion of inflammatory markers [IL-6 & NF-kB (p65)] and visfatin and increases adiponectin secretion in the inflamed mature adipocytes. HDL exhibits beyond its reverse cholesterol transporter property by exhibiting anti-inflammatory effects thru the deactivation of NF-ĸβ (p65). This may contribute to reducing the progression of obesity-related complications

Effects of palm oil derived tocotrienol rich fraction and vitamin e isomers on biomarkers of early atherogenesis in stimulated human umbilical vein endothelial cells

This study was conducted to investigate the effects of tocotrienol rich fraction (TRF), α-TOC, and pure TCT isomers (α-. γ- & δ-TCT) on inflammation, endothelial activation, nuclear factor kappa B (NFκB), endothelial nitric oxide synthase (eNOS) and monocyte binding activity (MBA) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with various concentrations of α-TOC, pure TCT isomers and TRF (0.3-10 μM) together with lipopolysaccharides (LPS) for 16 h. Culture medium and cells were collected and measured for the protein and gene expression of IL-6, TNF-α, NFκB, ICAM-1, VCAM-1, e-selectin, and eNOS. Monocyte binding activity (MBA) was measured by Rose Bengal staining. Area under the curve (AUC) analysis revealed that TRF and pure TCT particularly γ- and δ- isomers, showed better inhibition of inflammation and endothelial activation, MBA and greater eNOS increment than α-TOC. These suggest that TRF and pure TCT isomers have potential as preventive anti-atherogenic agents by attenuating the release of early biomarkers of atherogenesis which is better than α-TOC in LPS-stimulated human endothelial cells

Elucidation of the identification mechanism of murine embryonic cryotolerance through metabolomic analyses and the study of cellular ultrastructures / Nor Ashikin Mohamed Noor Khan

Cryopreservation of embryos is an essential procedure in all assisted conception units. Prediction of embryonic cryotolerance and developmental capacity after cryopreservation has previously relied on morphological assessment and observation on developmental capacity (Kuleshova et al., 2001; Han et al., 2003). Technological advancements in recent years has allowed for high-resolution microscopy in which details of ultrastructure at the organelle level may be used to select viable embryos for transfer (Dailey et al., 2006; Yamagata et al., 2009). In these studies, disruption to cytoskeletal components and mitochondrial distribution are observed and used in the selection of viable embryos. Although selection done based on qualitative morphological criteria produces valuable information on the physical damages after cryopreservation, the use of quantitative methods has proven to be more accurate in predicting survivability (Stokes, et al., 2007). Metabolomics is a useful quantitative tool to predict viability of embryos for transfer (Katz-Jaffe et al., 2009). With regard to metabolomics, amino acid turnover in the culture media (Houghton et al. 2002: Brison et al. 2007) and measurements of key functional groups using near-infrared spectroscopy (NIR) (Vergouw et al. 2009) has been used effectively to predict embryo developmental capacity

Antioxidant, Wound Healing Potential and In Silico Assessment of Naringin, Eicosane and Octacosane

1. Diabetic chronic wounds, mainly foot ulcers, constitute one of the most common complications of poorly managed diabetes mellitus. The most typical reasons are insufficient glycemic management, latent neuropathy, peripheral vascular disease, and neglected foot care. In addition, it is a common cause of foot osteomyelitis and amputation of the lower extremities. Patients are admitted in larger numbers attributable to chronic wounds compared to any other diabetic disease. In the United States, diabetes is currently the most common cause of non-traumatic amputations. Approximately five percent of diabetics develop foot ulcers, and one percent require amputation. Therefore, it is necessary to identify sources of lead with wound-healing properties. Redox imbalance due to excessive oxidative stress is one of the causes for the development of diabetic wounds. Antioxidants have been shown to decrease the progression of diabetic neuropathy by scavenging ROS, regenerating endogenous and exogenous antioxidants, and reversing redox imbalance. Matrix metalloproteinases (MMPs) play vital roles in numerous phases of the wound healing process. Antioxidant and fibroblast cell migration activity of Marantodes pumilum (MP) crude extract has previously been reported. Through their antioxidant, epithelialization, collagen synthesis, and fibroblast migration activities, the authors hypothesise that naringin, eicosane and octacosane identified in the MP extract may have wound-healing properties. 2. The present study aims to identify the bioactive components present in the dichloromethane (DCM) extract of M. pumilum and evaluate their antioxidant and wound healing activity. Bioactive components were identified using LCMS, HPTLC and GCMS. Excision wound on STZ-induced diabetic rat model, human dermal fibroblast (HDF) cell line and colorimetric antioxidant assays were used to evaluate wound healing and antioxidant activities, respectively. Molecular docking and pkCMS software would be utilised to predict binding energy and affinity, as well as ADME parameters. 3. Naringin (NAR), eicosane (EIC), and octacosane (OCT) present in MP displayed antioxidant action and wound excision closure. Histological examination HDF cell line demonstrates epithelialization, collagen production, fibroblast migration, polymorphonuclear leukocyte migration (PNML), and fibroblast movement. The results of molecular docking indicate a substantial attraction and contact between MMPs. pkCMS prediction indicates inadequate blood-brain barrier permeability, low toxicity, and absence of hepatotoxicity. 4. Wound healing properties of (NEO) naringin, eicosane and octacosane may be the result of their antioxidant properties and possible interactions with MMP