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        Lactobacillus Strains Alleviated Aging Symptoms and Aging-Induced Metabolic Disorders in Aged Rats

        HOR YAN YAN,Cheong-Hwa Ooi,Boon-Yin Khoo,Sy-Bing Choi,Azman Seeni,Shaharum Shamsuddin,Chern-Ein Oon,Kee-Leong Ong,정우식,Min-Tze Liong 한국식품영양과학회 2019 Journal of medicinal food Vol.22 No.1

        Aging is an inevitable and ubiquitous progress that affects all living organisms. A total of 18 strains of lactic acid bacteria (LAB) were evaluated on the activation of adenosine monophosphate-activated protein kinase (AMPK), an intracellular energy sensor mediating lifespan extension. The cell-free supernatant (CFS) of Lactobacillus fermentum DR9 (LF-DR9), Lactobacillus paracasei OFS 0291 (LP-0291), and Lactobacillus helveticus OFS 1515 (LH-1515) showed the highest activation of AMPK and was further evaluated. The phosphorylation of AMPK by these three LAB strains was more evident in U2OS and C2C12 cells, compared to the other cell lines and control (P < .05). Using premature senescent Sprague-Dawley rats induced by D-galactose (D-gal), the administration of LAB (10 log CFU/rat/day) for 12 weeks prevented the shortening of telomere length in D-gal-treated rats compared to the untreated control (P < .05). LF-DR9 lowered gene expression of p53, a known senescent biomarker, in gastrocnemius muscle and tibia compared to the control. The selected LAB strains also enhanced lipid, renal, and liver profile of rats, suggesting added potential of the strains in preventing aging-induced metabolic diseases. Strain LP-0291 and LH-1515 showed ability to adhere to mucin, no antibiotic resistance, tolerated and proliferated under gastric and intestinal simulated conditions, and inhibited the growth of pathogens Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis, comparable to commercial probiotic LF-DR9 and Lactobacillus sakei Probio 65. This study provided an insight into the potential of LAB for exhibiting antisenescence effects, with potentials as new medicinal foods for targeted antiaging therapies.

      • Effects of Rapamycin on Cell Apoptosis in MCF-7 Human Breast Cancer Cells

        Tengku Din, Tengku Ahmad Damitri Al-Astani,Seeni, Azman,Khairi, Wirdatul-Nur Mohd,Shamsuddin, Shaharum,Jaafar, Hasnan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

        Background: Rapamycin is an effective anti-angiogenic drug. However, the mode of its action remains unclear. Therefore, in this study, we aimed to elucidate the antitumor mechanism of rapamycin, hypothetically via apoptotic promotion, using MCF-7 breast cancer cells. Materials and Methods: MCF-7 cells were plated at a density of $1{\times}10^5$ cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations of rapamycin while only adding DMEM medium with PEG for the control regiment and grown at $37^{\circ}C$, 5% $CO_2$ and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated and rapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrast microscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation. In addition, cytotoxicity testing was performed using normal mouse breast mammary pads. Results: Our results clearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The $IC_{50}$ value of rapamycin on the MCF-7 cells was determined as $0.4{\mu}g/ml$ (p<0.05). Direct observation by inverted microscopy demonstrated that the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage, vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle showed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively. Conclusions: This study demonstrated that rapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphological changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis in late stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin as an anti-cancer agent.

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