Fucoidan⁻Fucoxanthin Ameliorated Cardiac Function via IRS1/GRB2/ SOS1, GSK3ß/CREB Pathways and Metabolic Pathways in Senescent Mice.

The effects of low molecular weight fucoidan (LMWF) in combination with high-stability fucoxanthin (HSFUCO) on cardiac function and the metabolic pathways of aging mice (Mus musculus) were investigated. We demonstrated that LMWF and HSFUCO could improve cardiac function in aging mice. Aging mice were treated with LMWF and HSFUCO, either on their own or in combination, on 28 consecutive days. Electrocardiography and whole-cell patch-clamp were used to measure QT interval and action potential duration (APD) of the subjects. Cardiac tissue morphology, reactive oxygen species, and Western blot were also applied. Ultra-high-performance liquid chromatography⁻quadrupole time-of-flight (UPLC-QTOF) mass spectrometry was used for investigating metabolic alterations. The use of LMWF and HSFUCO resulted in improvements in both ventricular rhythms (QT and APD). Treatment with fucoidan and fucoxanthin reduced the expression levels of SOS1 and GRB2 while increasing GSK3ß, CREB and IRS1 proteins expression in the aging process. Three main metabolic pathways, namely the TCA cycle, glycolysis, and steroid hormone biosynthesis, were highly enriched in the pathway enrichment analysis. When taken together, the LMWF and HSFUCO treatment improved both the ventricular rhythm and the muscular function of aging subjects by interfering with the metabolism and gene function.

PM2.5 induced cardiac hypertrophy via CREB/GSK3b/SOS1 pathway and metabolomics alterations.

The particle matter with diameter less 2.5µm (PM2.5) easier to adsorb toxic substance, and interfere with pulmonary gas exchange. In this study, cardioprotective effects of low molecular weight (LMW) fucoidan in cardiac hypertrophy subjects induced by PM2.5 exposure was conducted by measuring QT interval, Blood pressure, cardiac structure, metabolites and proteins expression in different organs. After PM2.5 exposure, increase in blood pressure, abnormal cardiac function (Prolongation of Action Potential Duration and QT Interval), and structral remodeling (cardiac hypertrophy and fibrosis) were recorded. Fucoidan supplement in consecutive 28 days can reduce the damage to myocardial injury caused by PM2.5. Clearance effect of fucoidan in serum, heart, kidney, lung and liver was found due to organic and inorganic compounds reduced SOS1, CREB, GSK3b, and GRB2 protein level were changed under PM2.5 exposure. Whereas, only CREB level was reduced after fucoidan treatment. Metabolic alteration was also determined that PM2.5 severely damage cardiac tissue and compromise its function. After treatment with fucoidan, the cardiac function was significantly recovered. Our finding demonstrated that LMW could enhance the cardiac status of mice with PM2.5 exposures by rescued QT interval prolongation, action potential and cardiac hypertrophy, and cardiac fibrosis decline.

Arsenic induces cardiac rhythm dysfunction and acylcarnitines metabolism perturbation in rats.

BACKGROUND: Arsenic has been shown to cause various diseases (such as blackfoot disease, cardiovascular diseases, bladder cancer and skin cancer) in many areas of the world. However, the effects of arsenic on cardiac rhythm functions still lack investigation. METHODS: In this study, different concentrations of arsenic were orally applied to Sprague Dawley rats in order to examine the relationship between arsenic and cardiovascular rhythm (i.e. long QT) via electrocardiography measurement. In addition, QT correction formulas were used to correct the QT interval. Linear regression analysis was used to examine the correlation between the QT interval and cardiac cycle length, corrected QT and heart rate. A metabolomic approach was applied to study carnitine-derived metabolites under arsenic exposure by using an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) system. RESULTS: The present findings showed that exposure to arsenic causes QT and corrected (QTc) prolongation and heart rate declines. However, the linear correlation analysis showed that there is no significant correlation between cardiac cycle length and the QT interval in both the uncorrected QT and corrected QT. The expression of acylcarnitine metabolites can be used to discriminate the control and arsenic-treated groups. CONCLUSIONS: This study provides information concerning the effect of arsenic at different concentrations on cardiac rhythm (such as QT, QTc, and heart rate) but not on cardiac cycle length. The metabolism of acylcarnitine metabolites can be a potential pathway for arsenic-induced cardiac rhythm dysfunction in rats.

Distinct expression of CDCA3, CDCA5, and CDCA8 leads to shorter relapse free survival in breast cancer patient.

Breast cancer is a dangerous disease that results in high mortality rates for cancer patients. Many methods have been developed for the treatment and prevention of this disease. Determining the expression patterns of certain target genes in specific subtypes of breast cancer is important for developing new therapies for breast cancer. In the present study, we performed a holistic approach to screening the mRNA expression of six members of the cell division cycle-associated gene family (CDCA) with a focus on breast cancer using the Oncomine and The Cancer Cell Line Encyclopedia (CCLE) databases. Furthermore, Gene Expression-Based Outcome for Breast Cancer Online (GOBO) was also used to deeply mine the expression of each CDCA gene in clinical breast cancer tissue and breast cancer cell lines. Finally, the mRNA expression of the CDCA genes as related to breast cancer patient survival were analyzed using a Kaplan-Meier plot. CDCA3, CDCA5, and CDCA8 mRNA expression levels were significantly higher than the control sample in both clinical tumor sample and cancer cell lines. These highly expressed genes in the tumors of breast cancer patients dramatically reduced patient survival. The interaction network of CDCA3, CDCA5, and CDCA8 with their co-expressed genes also revealed that CDCA3 expression was highly correlated with cell cycle related genes such as CCNB2, CDC20, CDKN3, and CCNB1. CDCA5 expression was correlated with BUB1 and TRIP13, while CDCA8 expression was correlated with BUB1 and CCNB1. Altogether, these findings suggested CDCA3, CDCA5, and CDCA8 could have a high potency as targeted breast cancer therapies.

Toxicological Evaluation of Low Molecular Weight Fucoidan in Vitro and in Vivo.

For a long time, fucoidan has been well known for its pharmacological activities, and recently low molecular weight fucoidan (LMF) has been used in food supplements and pharmaceutical products. In the present study, LMF was extracted from Laminaria japonica by enzyme hydrolysis. The toxicity of LMF in mouse and rat models was determined by many methods, such as total arsenic content, bacterial reverse mutation assay, chromosome aberration assay, and in vivo micronucleus assay. The present findings showed that LMF at 5000 µg/mL exhibited no mutagenicity. It also produced no formatting disruption of red blood cells in vivo. At 2000 mg/kg BW/day there were no toxicological indications. LMF is expected to be used as a safe food supplement.

The in vitro and in vivo effects of the low molecular weight fucoidan on the bone osteogenic differentiation properties.

Osteoporosis has been reported as a hidden death factor in aged people. So far, prevention and treatment therapies for osteoporosis only slow down the progress but do not treat the disease. Fucoidan has been recognized its roles in anti-tumor, anti-inflammatory, anti-coagulant and antiviral activities. To date, low molecular weight (LMW) fucoidan role in bone loss disease has been not determined yet. Therefore, this study aims to figure out potential effects of LMW fucoidan in osteoporosis in vitro and in vivo. LMW fucoidan was extracted from fresh Sargassum hemiphyllum showing a significant increase in 7F2 cell viability to 150.33 ± 6.50 % relative to normal fucoidan (130.12 ± 5.74 %). The expression of level BMP-2, ALP, osteocalcin significantly increased with 2.28 ± 0.06, 2.18 ± 0.12 and 2.06 ± 0.07 fold, respectively. The RT-PCR assay showed that LMW fucoidan increased mRNA expression of BMP-2, ALP, osteocalcin, COL I, BSP and osteonectin. Furthermore, the bone density and bone ash weight were considerably boosted by the oral administration of 280 mg/kg LMW fucoidan and 100 mg/kg calcium carbonate in C57BL/6J female aged mice. The present finding indicated that LMW fucoidan triggered osteogenic differentiation in vitro, and had an anabolic effect on bone mineralization in vivo. Dietary intake of LMW fucoidan from S. hemiphyllum suggested playing a role in the enhancement of bone loss with increasing age.