Hibiscus sabdariffa Linn. or also known as roselle which is rich in polyphenols, has been demonstrated to cause loweringof blood pressure in animal and clinical settings. However its exact mechanism of action particularly from polyphenoliccompounds is not clearly understood. Therefore, we aimed to determine the effects of H. sabdariffa polyphenol extract(HPE) towards vascular reactivity and its mechanism of action. The HPE was studied on isolated thoracic aortic ringsfrom normal Sprague-Dawley rats, suspended in a 15-ml organ chambers containing Krebs-Henseleit solution. Thechanges in tension were recorded by isometric transducer connected to data acquisition. HPE relaxed the contractioninduced by phenylephrine (PE, 1 μM) in similar pattern for both endothelium-intact and endothelium denuded aorticrings in dose-dependent manner 0.1 ~ 0.9 mg/ml. The pretreatment with atropine (1 μM), a competitive muscarinicantagonist, and propranolol (1 μM), a non-selective beta- blocker did not alter HPE vasorelaxation response. In addition,HPE did not inhibit the contraction induced by extracellular Ca2+ precontracted by PE (1 μM) or KCl (60 mM), in Ca2+-free solution, suggesting that the relaxation effect of HPE was not via inhibition of calcium channels. In conclusion,HPE demonstrated vasorelaxation effects on rat thoracic aorta although the underlying mechanism is still unknown.The vasorelaxation effect could be via angiotensin type 1 receptor inhibition in the vascular smooth muscle cells or theactivation of hyperpolarizing K+ chan

Vascular remodelling is an adaptive mechanism, which counteracts pressure changes in blood circulation. Nicotine content in cigarette increases the risk of hypertension. The exact relationship between nicotine and vascular remodelling still remain unknown. Current study was aimed to determine the effect of clinically relevant dosage of nicotine (equivalent to light smoker) on aortic reactivity, oxidative stress markers and histomorphological changes. Twelve age-matched male Sprague-Dawley rats were randomly divided into two groups, i.e.: normal saline as control or 0.6 mg/kg nicotine for 28 days (i.p., n=6 per group). On day-29, the rats were sacrificed and the thoracic aorta was dissected immediately for further studies. Mean arterial pressure (MAP) and pulse pressure (PP) of nicotine-treated vs. control were significantly increased (p<0.05). Nicotine-treated group showed significant (p<0.05) increase tunica media thickness, and decrease in lumen diameter, suggesting vascular remodelling which lead to prior hypertension state. The phenylephrine (PE)-induced contractile response in nicotine group was significantly higher than control group (ED50=1.44x10(5) M vs. 4.9x10(6) M) (p<0.05~0.001). However, nicotine-treated rat showed significantly lower endothelium-dependent relaxation response to acetylcholine (ACh) than in control group (ED50=6.17x10(7) M vs. 2.82x10(7) M) (p<0.05), indicating loss of primary vascular function. Malondialdehyde (MDA), a lipid peroxidation marker was significantly higher in nicotine group. Superoxide dismutase (SOD) enzymatic activity and glutathione (GSH) were all reduced in nicotine group (p<0.05) vs. control, suggesting nicotine induces oxidative imbalance. In short, chronic nicotine administration impaired aortic reactivity, probably via redox imbalance and vascular remodelling mechanism.
Acetylcholine ; Animals ; Aorta ; Aorta, Thoracic ; Arterial Pressure ; Blood Circulation ; Blood Pressure ; Glutathione ; Humans ; Hypertension ; Lipid Peroxidation ; Male ; Malondialdehyde ; Nicotine ; Oxidation-Reduction ; Oxidative Stress ; Phenylephrine ; Rats* ; Rats, Sprague-Dawley ; Relaxation ; Superoxide Dismutase ; Tobacco Products ; Tunica Media

Hypertension can be caused by various factors while the predominant causes include increase in body fluid volume and resistance in the circulatory system that elevate the blood pressure. Consumption of probiotics has been proven to attenuate hypertension; however, the effect is much strain-dependent. In this study, a newly isolated Lactobacillus casei (Lb. casei) strain C1 was investigated for its antihypertensive properties in spontaneously hypertensive rats (SHR). Lactic acid bacteria (LAB) suspension of 11 log colony-forming unit (CFU) was given to SHR (SHR+LAB, n=8), and phosphate buffer saline (PBS) was given as a control in SHR (SHR, n=8) and in Wistar rats as sham (WIS, n=8). The treatment was given via oral gavage for 8 weeks. The results showed that the weekly systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and aortic reactivity function were remarkably improved after 8 weeks of bacterial administration in SHR+LAB. These effects were mostly attributed by restoration of wall tension and tensile stress following the bacterial treatment. Although not statistically significant, the level of malondialdehye (MDA) in SHR+LAB serum was found declining. Increased levels of glutathione (GSH) and nitric oxide (NO) in SHR+LAB serum suggested that the bacterium exerted vascular protection through antioxidative functions and relatively high NO level that induced vasodilation. Collectively, Lb. casei strain C1 is a promising alternative for hypertension improvement.
Arterial Pressure ; Bacteria ; Blood Pressure ; Body Fluids ; Glutathione ; Hypertension ; Lactic Acid ; Lactobacillus casei* ; Lactobacillus* ; Nitric Oxide ; Probiotics ; Rats, Inbred SHR* ; Rats, Wistar ; Stem Cells ; Vasodilation

Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson’s disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann–Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.

COVID-19 ; Heart Diseases ; Humans ; Incidence ; SARS-CoV-2 ; Singapore/epidemiology*

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals. Methods: Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk. Results: Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality. Conclusions Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.