Yen-Chang Lin

Defective calcium inactivation causes long QT in obese insulin-resistant rat

The majority of diabetic patients who are overweight or obese die of heart disease. We suspect that the obesity-induced insulin resistance may lead to abnormal cardiac electrophysiology. We tested this hypothesis by studying an obese insulin-resistant rat model, the obese Zucker rat (OZR). Compared with the age-matched control, lean Zucker rat (LZR), OZR of 16-17 wk old exhibited an increase in QTc interval, action potential duration, and cell capacitance. Furthermore, the L-type calcium current (I(CaL)) in OZR exhibited defective inactivation and lost the complete inactivation back to the closed state, leading to increased Ca(2+) influx. The current density of I(CaL) was reduced in OZR, whereas the threshold activation and the current-voltage relationship of I(CaL) were not significantly altered. L-type Ba(2+) current (I(BaL)) in OZR also exhibited defective inactivation, and steady-state inactivation was not significantly altered. However, the current-voltage relationship and activation threshold of I(BaL) in OZR exhibited a depolarized shift compared with LZR. The total and membrane protein expression levels of Cav1.2 [pore-forming subunit of L-type calcium channels (LTCC)], but not the insulin receptors, were decreased in OZR. The insulin receptor was found to be associated with the Cav1.2, which was weakened in OZR. The total protein expression of calmodulin was reduced, but that of Cavβ2 subunit was not altered in OZR. Together, these results suggested that the 16- to 17-wk-old OZR has 1) developed cardiac hypertrophy, 2) exhibited altered electrophysiology manifested by the prolonged QTc interval, 3) increased duration of action potential in isolated ventricular myocytes, 4) defective inactivation of I(CaL) and I(BaL), 5) weakened the association of LTCC with the insulin receptor, and 6) decreased protein expression of Cav1.2 and calmodulin. These results also provided mechanistic insights into a remodeled cardiac electrophysiology under the condition of insulin resistance, enhancing our understanding of long QT associated with obese type 2 diabetic patients.

Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed exert prebiotics and anti-inflammatory activities in Caco-2 cells

Background The aim of this study is to investigate the anti-inflammatory effects of low-molecular-weight fucoidan (LMF) and high-stability fucoxanthin (HS-Fucox) in a lipopolysaccharide-induced inflammatory Caco-2 cell line co-culture with B. lactis. Methods We used various methods such as transepithelial resistance (TER) assay, cytokine secretion assay, and tight junction protein mRNA expression assay to examine LMF and HS-Fucox anti-inflammatory properties. Results LMF and HS-Fucox activated probiotic growth and reduced the inflammation of the intestinal epithelial cells. Moreover, the combination of LMFHS-Fucox dramatically enhanced the intestinal epithelial barrier and immune function against the lipopolysaccharide effect by inhibiting IL-1β and TNF-α and promoting IL-10 and IFN-γ. Conclusion These findings suggested that LMF and HS-Fucox, alone or in combination, could be the potential natural compounds to enhance the immune system and have an anti-inflammatory effect on the intestinal cells.

The role of nodose ganglia in the regulation of cardiovascular function following pulmonary exposure to ultrafine titanium dioxide

Abstract The inhalation of nanosized air pollutant particles is a recognised risk factor for cardiovascular disease; however, the link between occupational exposure to engineered nanoparticles and adverse cardiovascular events remains unclear. In the present study, the authors demonstrated that pulmonary exposure of rats to ultrafine titanium dioxide (UFTiO2) significantly increased heart rate and depressed diastolic function of the heart in response to isoproterenol. Moreover, pulmonary inhalation of UFTiO2 elevated mean and diastolic blood pressure in response to norepinephrine. Pretreatment of the rats ip with the transient receptor potential (TRP) channel blocker ruthenium red inhibited substance P synthesis in nodose ganglia and associated functional and biological changes in the cardiovascular system. In conclusion, the effects of pulmonary inhalation of UFTiO2 on cardiovascular function are most likely triggered by a lung-nodose ganglia-regulated pathway via the activation of TRP channels in the lung.

Highly efficient adsorption of dyes by biochar derived from pigments-extracted macroalgae pyrolyzed at different temperature

Biochar is known to efficiently adsorb dyes from wastewater. In this study, biochar was derived from macroalgae residue by pyrolysis, and the influence of varying temperature (from 400 °C to 800 °C) on biochar characteristics was investigated. Among the biochar samples tested, macroalgae-derived biochar possessing highly porous structure, special surface chemical behavior and high thermal stability was found to be efficient in removing malachite green, crystal violet and Congo red. The biochar derived by pyrolysis at 800 °C showed the highest adsorption capacity for malachite green (5306.2 mg g-1). In this study, the transformation of microalgae residue into a highly efficient dye adsorbent is a promising procedure for economic and environmental protection.

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.

Cardiovascular effects in rats after intratracheal instillation of metal welding particles

Abstract Studies have indicated that pulmonary exposure to welding fumes can induce a series of adverse effects in the respiratory system, including infection, bronchitis, siderosis and decreased pulmonary function. Recent clinical and epidemiological studies have found that pulmonary exposure to welding fumes is also associated with a higher incidence of cardiovascular events. However, there is insufficient evidence to confirm a direct effect of welding fumes on the cardiovascular system. The present study investigated the effects of pulmonary exposure to welding fumes on the heart and the vascular system in rats. Two chemically distinct welding fumes generated from manual metal arc-hard surfacing (MMA-HS) and gas metal arc-mild steel (GMA-MS) welding were tested. Three groups of rats were instilled intratracheally with MMA-HS (2 mg/rat), GMA-MS (2 mg/rat) or saline as control once a week for seven weeks. On days 1 and 7 after the last treatment, basal cardiovascular function and the cardiovascular response to increasing doses of adrenoreceptor agonists were assessed. MMA-HS treatment reduced the basal levels of left ventricle end-systolic pressure and dP/dtmax at 1 day post-treatment, and decreased dP/dtmin in response to isoproterenol (ISO) at 7 days post-treatment. Unlike MMA-HS, GMA-MS only affected left ventricular end-diastolic pressure in response to ISO at 7 days post-treatment. Treatment with MMA-HS or GMA-MS did not alter heart rate and blood pressure. Our findings suggest that exposure to different welding fumes can induce different adverse effects on the cardiovascular system, and that cardiac contractility may be a sensitive indicator of cardiovascular dysfunction.

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor.

Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1-30 μg/kg) decreased resting heart rate; at high doses (150-300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03-0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias.

A mechanism of low molecular weight fucoidans degraded by enzymatic and acidic hydrolysis for the prevention of UVB damage

Fucoidans have been long used as a food supplement due to their diverse pharmacological effects on human health. Low molecular weight fucoidan (LF) is a common form of fucoidans that has been shown to have enhanced biological activity. In the present study, fucoidans were extracted from the brown alga Sargassum hemiphyllum and enzyme-hydrolyzed into low and high molecular weight fucoidans (HF). The skin protective effects of LF, HF, and other fucoidans derivatives against ultraviolet B (UVB) damage were determined by measuring the expression levels of matrix metalloproteinase genes encoding collagenases (MMP-1, MMP-2, MMP-8, MMP-9, MMP-13), transforming growth factor β receptor II (TGFβRII), and type I procollagen. The results show that LF protects against UVB damage to the skin by inhibiting UVB-induced transcription factor activator protein-1 (AP-1)-stimulated transcription of MMP genes encoding collagenases (MMP-1, MMP-8, and MMP-13) and increasing TGFβRII mRNA levels to prevent the loss of TGFβRII that occurs during UVB-induced collagen degradation. Moreover, this study reveals that the biological properties of fucoidans are highly dependent on the fucose content, sulfate content, and molecular weight.

The novel regulations of MEF2A, CAMKK2, CALM3, and TNNI3 in ventricular hypertrophy induced by arsenic exposure in rats.

Arsenic is a ubiquitous toxic compound that exists naturally in many sources such as soil, groundwater, and food; in which vast majority forms are arsenite (As(3+)) or arsenate (As(5+)). The mechanism of arsenic detoxification in humans still remains obscured. Epidemiologic studies documented that arsenic pollution caused black foot disease, cardiovascular diseases (hypertension, hypotension, cardiomyopathy), bladder cancer and skin cancer in many countries in which Taiwan is considered as high arsenic exposure country for long time ago. However, the effects of arsenic to cardiac functions still lacked of investigation while some studies mainly focus on inflammatory and cancer mechanisms. In the present study, we found cardiac hypertrophy signaling may be the most significant pathway for up regulated genes in arsenic exposed patients via bioinformatics approach. To verify our bioinformatics prediction, arsenic was fed orally to rats at different concentration based on previous studies in Taiwan. Using hemodynamic method as the main tool to measure the changes in blood pressure, left ventricular pressure and left ventricular contractility index, the findings suggest that highly exposure to arsenic lead to hypertension; elevated left ventricular diastolic pressure and alteration in cardiac contractility which are supposed to be the interaction between arsenic and cardiac nerves activity via the changing in calcium homeostasis. Collectively, based on our real-time PCR and western blot data strongly suggest that calcium homeostasis may also go through MEF2A, TNNI3, CAMKK2, CALM3 and cardiac hypertrophy relative signaling pathway.

Type 1 Diabetes, Cardiovascular Complications and Sesame (芝麻 Zhī Má)

Diabetes is a major concern among medical practitioners, with the annual mortality rate increasing up to 26.9% in a person aged 65 years or older and 11.3% in the adult. There are many serious complications associated with diabetes, particularly cardiovascular complications due to microvascular diseases. A prerequisite to reduce the risk of microvascular and neurologic complications of type 1 diabetes is normoglycemia. Insulin therapy is the most common treatment used nowadays in type 1 diabetes. However, this method still has many disadvantages such as increased episode of severe hypoglycemia, hypoglycemia unawareness, increased weight gain, transient exacerbation of pre-existing retinopathy, etc. Using insulin pump (the insulin pump is a medical device used for continuous subcutaneous insulin infusion to manage the insulin level in the treatment of diabetes mellitus), is associated with known disadvantages including increased ketoacidosis, infection at the infusion site, and the treatment being less suitable in young children (less than 7 years of age). Therefore, alternative treatment for diabetes is still in great demand. We took the approach of traditional Chinese medicine to discuss this matter. Sesame (芝麻 Zhī Má), a herb, has been used medicinally for thousands of years in almost all the countries in the world. The beneficial effects of sesame in remediating diabetes, such as hypoglycemic effects, antioxidant, anti-inflammatory, and hypolipidemic effects, improving fat metabolism, and reducing cholesterol, have been demonstrated in many studies,. However, reports on the effects of sesame in remediating cardiovascular complications in diabetic patients are limited, which necessitates further studies on the effects of sesame on cardiovascular complications.