No abstract

Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials.Nutrients 2020, 12, 259 2 of 84 Nutrients 2020, 12, 259 4 of 84 the order δ > γ > β > α [45]. Using HepG2 cells, γT3 was shown to stimulate apolipoprotein B (Apo-B) degradation by decreasing its translocation into the endoplasmic reticulum (ER) lumen. This action eventually caused a reduction in the number of Apo-B in lipoprotein particles [46]. Other reports showed that γT3 and δT3 had the potential to reduce the hepatic TG synthesis and very-low-density lipoprotein (VLDL) secretion by suppressing expression of genes involved in lipid homeostasis, particularly the TG, cholesterol, and VLDL biosynthesis. Moreover, δT3 also promoted the efflux of LDL through LDL receptor expression [47]. A summary of the literature on effect of T3 supplementation on lipid profile of hypercholesterolemic model in vitro is shown in Table 1.Animal models of dyslipidemia have been used to investigate the effects of T3 on lipid profile. Several animals have been tested, including chicken, swine and rodents (rats, hamsters, guinea pigs). In chickens fed with a varying level of αTF and γT3, Qureshi et al. (1996) showed that αTF enhanced the inhibition of HMGCR by γT3. They further stipulated that the vitamin E mixture should contain 15-20% of αTF and approximately 60% of γT3 or δT3 for optimal anti-cholesterol effects [48]. In the subsequent study, demonstrated that combination of 50 ppm T3-rich fraction (TRF) and 50 ppm lovastatin was more effective in suppressing HMGCR activity compared to lovastatin alone in chickens. The combination also reduced serum TC and LDL-C, TG, Apo-B, thromboxane B 2 , and platelet factor 4 in contrast to individual treatment [49]. Using chicken supplemented with 50 ppm of δT3, Qureshi et al. (2011) further revealed that δT3 reduced TC and LDL-C besides suppressing the lipid elevating effects of dexamethasone and potentiated the TG-lowering effect of riboflavin [50]. Using genetically hypercholesterolemic swine, Qureshi et al. (1991) demonstrated the significant effect of TRF in lowering serum TC, LDL-C, Apo-B, thrombo...

Objectives: This prospective, observational all-comers registry assessed the safety and efficacy of a Drug Coated Balloon-only strategy (DCB-only) in patients with coronary lesions.Background: Data regarding the performance of a DCB-only approach, especially in patients with previously untreated de-novo coronary artery disease (CAD), are still limited.Methods: This study was conducted as an international, multicenter registry primarily enrolling patients with de-novo CAD. However, it was also possible to include patients with in-stent restenosis (ISR). The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) after 9 months.Results: A total of 1,025 patients with a mean age of 64.0 ± 11.2 years were enrolled. The majority of treated lesions were de-novo (66.9%), followed by drug-eluting-stent ISR (DES-ISR; 22.6%) and bare-metal-stent ISR (BMS-ISR; 10.5%). The TLR rate was lower in the de-novo group (2.3%) when compared to BMS-(2.9%) and DES-ISR (5.8%) (P = 0.049). Regarding MACE, there was a trend toward fewer events in the de-novo group (5.6%) than in the BMS-(7.8%) and DES-ISR cohort (9.6%) (P = 0.131). Subgroup analyses revealed that lesion type (95% CI 1.127-6.587); P = 0.026) and additional stent implantation (95% CI 0.054-0.464; P = 0.001) were associated with higher TLR rates. Conclusions:Our results show that DCB-only angioplasty of de-novo coronary lesions is associated with low MACE and TLR rates. Thus, DCBs appear to be an attractive alternative for the interventional, stentless treatment of suitable de-novo coronary lesions. K E Y W O R D Scoronary intervention, devices, MACE, TLR, tools

Objectives. We analyzed the efficacy of drug coated balloons (DCB) as a stand-alone-therapy in de novo lesions of large coronary arteries. DCBs seem to be an attractive alternative for the stent-free interventional treatment of de novo coronary artery disease (CAD). However, data regarding a DCB-only approach in de novo CAD are currently limited to vessels of small caliber. Methods. By means of propensity score (PS) matching 234 individuals with de novo CAD were identified with similar demographic characteristics. This patient population was stratified in a 1:1 fashion according to a reference vessel diameter cut-off of 2.75 mm in small and large vessel disease. The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) at 9 months. Results. Patients with small vessel disease had an average reference diameter of 2.45 ± 0.23 mm, while the large vessel group averaged 3.16 ± 0.27 mm. Regarding 9-month major adverse cardiac event (MACE), 5.7% of the patients with small and 6.1% of the patients with large vessels had MACE (p=0.903). Analysis of the individual MACE components revealed a TLR rate of 3.8% in small and 1.0% in large vessels (p=0.200). Of note, no thrombotic events in the DCB treated coronary segments occurred in either group during the 9-month follow-up. Conclusions. Our data demonstrate for the first time that DCB-only PCI of de novo lesions in large coronary arteries (>2.75 mm) is safe and as effective. Interventional treatment for CAD without permanent or temporary scaffolding, demonstrated a similar efficacy for large and small vessels.