A randomized controlled trial on the effects of traditional Thai mind-body exercise (Ruesi Dadton) on biomarkers in mild cognitive impairment.

BACKGROUND: Exercise has been shown to reduce the rate of mild cognitive impairment (MCI) and Alzheimer's disease. Although motor coordination movements and poses in Ruesi Dadton (RD) exercises may improve cognitive function, RD is rarely used for MCI. To date, there is insufficient evidence on whether 12 weeks of RD exercise correlates with blood biomarkers related to neurogenesis and plasticity. AIM: To determine the effects on blood biomarkers of 12-week RD in MCI. DESIGN: Two-group parallel randomized controlled trial. SETTING: Community exercise. POPULATION: Individual with MCI. METHODS: Fifty-eight participants (n.=29 in each group). The RD group performed 60min of RD exercises (15 poses) three times weekly for 12 weeks. The control group received no intervention. In addition, both groups were given information regarding MCI symptoms by the physician on the first day. Peripheral blood was collected to measure serum brain-derived neurotrophic factor (BDNF) and sirtuin 1 (SIRT1) levels before and after intervention. RESULTS: The effects of 12-week RD pre- and post-intervention were examined using 2×2 repeated multivariate analyses, which showed significant differences in interaction by group and time. Student's t tests and paired t tests were employed in subsequent analyses to evaluate between-group and within-group differences for both biomarkers. CONCLUSIONS: In each test, we discovered increased levels of BDNF and SIRT1 in the RD group but not in the control group. These findings suggested that RD could benefit MCI patients through enhanced BDNF and SIRT1 levels. CLINICAL REHABILITATION IMPACT: Twelve weeks of RD might be helpful to patients with MCI and older people who experience cognitive impairment by improving blood biomarkers responsible for brain plasticity and amyloid plaque degradation.

Effects of Oxidative Damage during Ruesi Dadton Exercise in Mild Cognitive Impairment: Randomized Controlled Trial.

This study aimed to investigate the effect of biomarkers of oxidative stress (OS) in 8-isoprostane (8-iso) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) on mild cognitive impairment (MCI) during a 12-week Ruesi Dadton (RD) exercise. A total of 274 enrolled participants were classified into blocks based on age and formal educational years, and randomly assigned into two groups: RD and control (CON). The participants' cognitive functions were tested using Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores to screen for MCI. Urine samples of approximately 30 mL were collected from both groups pre- and post-intervention. All participants signed consent forms before participating in the program. Participants in the RD group were instructed to perform 15 postures of RD exercise in 60 min, three times a week for 12 weeks. A 2 × 2 (group × time) repeated multivariate analysis, with MoCA score, 8-iso, and 8-OH-dG as covariates, was performed to analyze the between-subject differences across group [V = 0.143, F(2,60) = 5.020, p = 0.010, d = 0.209] and within-subject differences across interaction between group [V = 0.143, F(2,60) = 5.020, p = 0.010, d = 0.408]. There were significant differences from univariate data regarding both 8-iso (F1,61 = 10.081, P = 0.002, d = 0.406) and 8-OH-dG (F(1,61) = 5.965, P = 0.018, d = 0.312) levels. Moreover, results from both biomarkers in the RD group revealed significant improvements in 8-iso (p < 0.001) and 8-OH-dG (p = 0.003), whereas there were no improvements in the CON group. In conclusion, RD decreased biomarkers of OS during 12 weeks of RD exercise in MCI. These results indicate that in MCI, RD could improve lipid peroxidation and DNA oxidation by 8-iso and 8-OH-dG, respectively.

Traditional Thai exercise (Ruesi Dadton) for improving motor and cognitive functions in mild cognitive impairment: a randomized controlled trial.

This study determined the effectiveness of a 12-week cycle of Ruesi Dadton (RSD) among older adults with mild cognitive impairment (MCI), for improving cognitive and physical performance. Seventy-six participants were included and were divided equally into two groups. A group performed RSD exercise for 60 min, 3 times/wk for 12 weeks, and the control group did not perform RSD exercise. The primary endpoint was cognitive function, as assessed by the Montreal cognitive assessment (MoCA), Mini-Mental State Examination, verbal fluency (VF) test, and trail making test parts A and B (TMT-A and TMT-B). The secondary endpoints were the Timed Up and Go (TUG) test, handgrip, and gait speed results, which were used to evaluate the physical function. There were significant differences in the TMT-B and handgrip scores (P<0.05) between the two groups. Both groups had improved MoCA scores (P<0.05) and normal walking speeds (P<0.01). Additionally, the RSD group showed improved VF test (P<0.01), TMT-B (P<0.01), and TUG test (P<0.05); a negative correlation was found between MoCA and TUG test (P<0.05). However, high walking speed and handgrip (P<0.05) worsened in the control group. RSD exercise resulted in relevant improvements in the cognitive and physical functions in MCI.

Etlingera elatior Extract promotes cell death in B16 melanoma cells via down-regulation of ERK and Akt signaling pathways.

BACKGROUND: Torch ginger (Etlingera elatior, EE) is a ginger plant that found in Southeast Asia. Previous study showed its flowers and leaves composed of several flavonoids with anti-cancer activity. This study aims to investigate the mechanism of EE extract on cell death induction in melanoma cells. METHODS: To carry out this study, the cytotoxic effect of EE extract was performed using MTT assay. Nuclear morphological change and loss of mitochondrial membrane potential were observed using Hoechst 33,342 and JC-1 staining. Flow cytometry using Annexin V/PI double staining assessed apoptosis, necrosis and viability. Caspase activity was detected by caspase activity kits. The expression of Bcl-2 family proteins, ERK and Akt signaling pathways were examined by Western blot analysis. RESULTS: The treatment of EE extract resulted in a dose- and time-dependent reduction in cell viability in B16 cells. It also induced nuclear condensation, phosphatidylserine exposure, and loss of mitochondrial membrane potential, which are markers of apoptosis. Furthermore, the expression of Bim was increased instead of Bax and Bcl-2. The results also showed caspase-independent activity and the down-regulation of ERK and Akt signaling pathway. CONCLUSION: The results suggest that EE extract induced caspase-independent cell death via down-regulation of ERK and Akt pathways in B16 cells. This may be beneficial as a chemopreventive or chemotherapeutic agent in melanoma treatment.

Apoptosis induction associated with the ER stress response through up-regulation of JNK in HeLa cells by gambogic acid.

BACKGROUND: Gambogic acid (GA) was extracted from the dried yellow resin of gamboge (Garcinia hanburyi) which is traditionally used as a coloring material for painting and cloth dying. Gamboge has been also used as a folk medicine for an internal purgative and externally infected wound. We focused on the mechanisms of apoptosis induction by GA through the unfold protein response (ER stress) in HeLa cells. METHODS: The cytotoxic effect of GA against HeLa cells was determined by trypan blue exclusion assay. Markers of ER stress such as XBP-1, GRP78, CHOP, GADD34 and ERdj4 were analyzed by RT-PCR and Real-time RT-PCR. Cell morphological changes and apoptotic proteins were performed by Hoechst33342 staining and Western blotting technique. RESULTS: Our results indicated a time- and dose-dependent decrease of cell viability by GA. The ER stress induction is determined by the up-regulation of spliced XBP1 mRNA and activated GRP78, CHOP, GADD34 and ERdj4 expression. GA also induced cell morphological changes such as nuclear condensation, membrane blebbing and apoptotic body in Hela cells. Apoptosis cell death detected by increased DR5, caspase-8, -9, and -3 expression as well as increased cleaved-PARP, while decreased Bcl-2 upon GA treatment. In addition, phosphorylated JNK was up-regulated but phosphorylated ERK was down-regulated after exposure to GA. CONCLUSIONS: These results suggest that GA induce apoptosis associated with the ER stress response through up-regulation of p-JNK and down-regulation of p-ERK in HeLa cells.

Antiproliferative effect of α-mangostin on canine osteosarcoma cells.

Osteosarcoma is the most frequently diagnosed primary bone tumor in dog. Since chemotherapeutics are quite limited due to high cost and severe toxicity, therefore, the ultimate goal is to discover cost-effective therapeutics with less toxicity. We have studied the effect of α-mangostin, a xanthone derivative isolated from pericarp of mangosteen (Garcinia mangostana Linn.) in canine osteosarcoma, D-17 cells. The results showed that α-mangostin induced antiproliferation with IC(50) at 15 µg/ml. Hoechst 33342 nuclear staining and nucleosomal DNA-gel electrophoresis revealed that α-mangostin could induce nuclear condensation and fragmentation, typically seen in apoptosis. Cell cycle analysis demonstrated that α-mangostin induced sub-G1 peak. In addition, α-mangostin also induced membrane flipping of the phosphatidylserine and the loss of mitochondrial membrane potential in D-17 cells. In conclusion, α-mangostin, induced apoptotic cell death against canine osteosarcoma D-17 cells, could be a potential candidate for preventive and therapeutic application for bone cancer treatment in dogs.

α-Mangostin induces apoptosis in human chondrosarcoma cells through downregulation of ERK/JNK and Akt signaling pathway.

Chondrosarcoma is a malignant primary bone tumor that is resistant to chemotherapy and radiation therapy. α-Mangostin, a component of Garcinia mangostana Linn, is a xanthone derivative shown to have antioxidant and antitumor properties. This study is the first to investigate anticancer effects of α-mangostin in the human chondrosarcoma cell line SW1353. We showed that α-mangostin inhibited cell proliferation of SW1353 cells in a time- and dose-dependent manner by using the trypan blue exclusion method. Hoechst 33342 nuclear staining and nucleosomal DNA-gel electrophoresis revealed that α-mangostin could induce nuclear condensation and fragmentation, typically seen in apoptosis. Flow cytometry using Annexin V/PI double staining assessed apoptosis, necrosis and viability. α-Mangostin activated caspase-3, -8, -9 expression, decreased Bcl-2 and increased Bax. This promotes mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm. In addition, total and phosphorylated ERK and JNK were downregulated in α-mangostin-treated SW1353 cells but no changes in p38. α-Mangostin also decreased phosphorylated Akt without altering total Akt. These results suggest that α-mangostin inhinbited cell proliferation and induced apoptosis through downregulation of ERK, JNK and Akt signaling pathway in human chondrosarcoma SW1353 cells.

High transfection efficiency of cationic lipids with asymmetric acyl-cholesteryl hydrophobic tails.

The ability of a nonviral gene delivery system to overcome extra- and intracellular barriers is a critical issue for the future clinical applications of gene therapy. In recent years much effort has been focused on the development of a variety of DNA carriers, and cationic liposomes have become the most common nonviral gene delivery system. One hundred and eighty novel cationic lipids with asymmetric acyl-cholesteryl hydrophobic tails were synthesized by parallel solid-phase chemistry. The liposomes were prepared and gel retardation assays were used to study the binding efficiency between the prepared liposome and the DNA. Transfection efficiencies of the lipids were evaluated against various mammalian cells, such as human embryonic kidney (HEK293), human cervical adenocarcinoma (HeLa), canine osteosarcoma (D17), colorectal adenocarcinoma (COLO 205), and human prostate adenocarcinoma (PC3) cells. The lipids with an acyl portion at the terminal part of the polyamine backbone exhibited higher transfection efficiency than those with the acyl portion as an internal part of the backbone. These compounds also showed higher transfection efficiency and lower cytotoxicity than the commercially available agents, Effectene, DOTAP, and DC-Chol.

Solid phase synthesis of novel asymmetric hydrophilic head cholesterol-based cationic lipids with potential DNA delivery.

Twenty-four asymmetric divalent head group cholesterol-based cationic lipids were designed and synthesized by parallel solid phase chemistry. These asymmetric head groups composed of amino functionality together with trimethylamino, di(2-hydroxyethyl)amino or guanidinyl groups. Spacers between cationic heads and linker were both equal and unequal in length. These lipids were subjected to evaluation for DNA binding affinities by gel retardation assay and were screened for their transfection efficiency on HEK293 cells. Cationic lipids with equal chain length exhibited high transfection efficiency when polar part contained asymmetric polar heads. In contrast, lipids with unequal chain length exhibited high transfection efficiency when polar part contained symmetric heads. According to the optimal formulation, seven lipids exhibited higher transfection efficiency than the commercially available transfection agents, Effectene, DOTAP and DC-Chol, to deliver DNA into PC3 human prostate adenocarcinoma cells. 3beta-[N-(N'-Guanidinyl)-2'-aminoethyl)-N-(2-aminoethyl)carbamoyl] cholesterol (5) bearing amino and guanidinyl polar heads exhibited highest transfection efficiency with minimal toxicity. The morphology of active liposomes was observed by transmission electron microscopy (TEM) and size of liposomes were around 200-700 nm.

Hydrogen production and anaerobic decolorization of wastewater containing Reactive Blue 4 by a bacterial consortium of Salmonella subterranea and Paenibacillus polymyxa.

Anaerobic biodegradability of wastewater (3,000 mg CODcr/l) containing 300 mg/l Reactive Blue 4, with different co-substrates, glucose, butyrate and propionate by a bacterial consortium of Salmonella subterranea and Paenibacillus polymyxa, concomitantly with hydrogen production was investigated at 35 degrees C. The accumulative hydrogen production at 3,067 mg CODcr/l was obtained after 7 days of incubation with glucose, sludge, the bacterial consortium. The volatile fatty acids, residual glucose and the total organic carbon were correlated to hydrogen obtained. Interestingly, the bacterial consortium possess decolorization ability showing approximately 24% dye removal after 24 h incubation using glucose as a co-substrate, which was about two and eight times those of butyrate (10%), propionate (12%) and control (3%), respectively. RB4 decolorization occurred through acidogenesis, as high volatile fatty acids but low methane was detected. The bacterial consortium will be the bacterial strains of interest for further decolorization and hydrogen production of industrial waste water.

High transfection efficiency and low toxicity cationic lipids with aminoglycerol-diamine conjugate.

The solid phase synthesis of a library of aminoglycerol-diamine conjugate-based transfection agents having urea linkage between diverse length of diamines and various lengths of hydrophobic tails is described. These compounds were characterized and structure-activity relationships were determined for DNA binding and transfection ability when formulated as cationic liposomes. Cationic lipids with short spacer length and short hydrophobic tails bound to DNA and delivered DNA into HEK293 cells more efficient than those with longer ones. Transfection efficiency of some of the cationic liposomes was superior to that of the commercial transfection agents, Effectene, DOTAP and DC-Chol. The lipids 6Ab and 6Bb did not require the helper lipid DOPE to produce high-efficiency transfection of human cells while displaying minimal cytotoxicity. This suggests that these newly described aminoglycerol-based lipids should be very promising in liposome-mediated gene delivery and illustrate the potential of solid phase synthesis method for non-viral vector discovery.