Platelet MicroRNA 365-3p Expression Correlates with High On-treatment Platelet Reactivity in Coronary Artery Disease Patients.

PURPOSE: The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. METHODS: Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. RESULTS: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls. CONCLUSIONS: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response. CLINICAL TRIAL REGISTRATION: NCT02101437.

Pseudogene: lessons from PCR bias, identification and resurrection.

Pseudogenes are fragments of non-functional genomic DNA with high sequences similarity to normal functional genes. They are a kind of non-coding DNA produced by gene duplications or retrotranspositions. Pseudogenes exist in human genome at a large quantity which is nearly as much as that of normal functional genes. They could cause PCR bias in molecular biology experiments and confuse related analysis. On the other hand, pesudogenes are important elements in genomics study for getting an integral picture of genome annotation. They give diverse information of evolutionary history and are regarded as genome fossils. Worldwide research project "encyclopedia of DNA elements"(ENCODE) founded in recent years have enhanced our understanding of pseudogenes. Approaches established to identify pseudogenes include PseudoPipe, HAVANA method, PseudoFinder, RetroFinder, GIS-PET method and consensus method. This paper discuss pseudogenes with respect to the formation mechanisms, distribution, and problems for PCR, importance and identification of pseudogenes. Furthermore, potential resurrection of pseudogenes and their potential function are discussed.

Insecticide Resistance, and Its Effects on Bait Performance in Field-Collected German Cockroaches (Blattodea: Ectobiidae) From Taiwan.

Insecticide resistance in the German cockroach, Blattella germanica (L.), is a significant challenge to the pest management professionals worldwide. We collected 24 field populations of B. germanica from different localities in Taiwan island, reared them for one to two generations, and evaluated them for their resistance to deltamethrin, propoxur, and fipronil using the surface-contact method. Results showed that deltamethrin resistance ratio ranged from 1.5 to 817.5×. Among the strains, TC Supermarket, TC Sanshang Logistics, TC THSR, and TC 1Taichungsteak strains showed very high resistance to deltamethrin, which mortality ranged between 0 and 33% at 7-d post-treatment. On the other hand, resistance to propoxur and fipronil RR were 0.70-7.13× and 1.67-3.72×, respectively. Synergism studies using piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioate (DEF) suggested the major involvement of cytochrome P450 monooxygenase and minor involvement of esterases. However, deltamethrin resistance in two strains (i.e., TC Supermarket and TC THSR) was not affected by both PBO and DEF, indicating that other mechanisms are involved in the resistance, including kdr resistance. Evaluation of the field strains using commercial gel baits containing fipronil, imidacloprid, hydramethylnon, and indoxacarb for up to 7 d resulted in 24.4-100%, 11.3-78.5%, 15.8-75.5%, and 63.3-100% mortality, respectively. We found that high deltamethrin resistance in some strains could affect the performance of fipronil, imidacloprid, and indoxacarb baits, indicating the potential involvement of cytochrome P450 monooxygenase in reducing the effectiveness of the bait toxicants.

DAPT Plus Cilostazol is Better Than Traditional DAPT or Aspirin Plus Ticagrelor as Elective PCI for Intermediate-to-Highly Complex Cases: Prospective, Randomized, PRU-Based Study in Taiwan.

PURPOSE: Current treatment guidelines do not recommend different antiplatelet treatments for patients in different coronary risk categories; nor do they consider ethnic differences in responses to individual drugs. OBJECTIVES: We performed a prospective, single-blind, randomized, comparative study of Taiwanese patients with stable angina and scheduled stent implantation for intermediate-to-highly complex coronary lesions and compared the platelet reactivity unit (PRU) levels and 24-month outcomes of groups receiving three different antiplatelet treatments. METHODS: Patients (N = 334) were randomized into three treatment groups (aspirin + clopidogrel, aspirin + ticagrelor, or aspirin + clopidogrel + cilostazol) for 6 months of treatment and were then switched to aspirin only. PRU levels were determined 24 h, 7 days, and 1 month after stent implantation. Clinical outcomes and adverse events were recorded over 24 months. RESULTS: Clopidogrel treatment reached full effect after 1 month. Ticagrelor decreased PRU levels more than did clopidogrel but often to levels that increased the risk of hemorrhage. The addition of cilostazol to clopidogrel decreased PRU levels earlier and more strongly than clopidogrel alone but not as strongly as did ticagrelor. Ticagrelor treatment caused fewer major adverse cardiovascular events (MACEs) and more episodes of minor bleeding than the other two treatments. CONCLUSIONS: Clopidogrel appears safer than ticagrelor in Taiwanese patients with stable angina after stent implantation for intermediate-to-highly complex coronary lesions. The addition of cilostazol to clopidogrel may provide a more rapid decrease in PRU to therapeutic levels without increasing the risk of hemorrhage. CLINICAL TRIAL REGISTRATION NUMBER: NCT02101411.