MiR-140-5p targets BCL2L1 to promote cardiomyocyte apoptosis.

The article "MiR-140-5p targets BCL2L1 to promote cardiomyocyte apoptosis, by M.-Y. Sun, L.-P. Li, published in Eur Rev Med Pharmacol Sci 2020; 24 (11): 6311-6322-DOI: 10.26355/eurrev_202006_21529-PMID: 32572928" has been withdrawn from the authors. They stated that "they are still working on this study" and that "they found some current experimental results which are inconsistent with the previous ones. Moreover, they added that "these inconsistent results may be caused by the contamination of the previous experimental cell lines". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21529.

MiR-140-5p targets BCL2L1 to promote cardiomyocyte apoptosis.

OBJECTIVE: Recovery of blood flow after ischemic cardiomyopathy can lead to aggravation of myocardial injury. This is very detrimental to the patient's prognosis. The purpose of this study was to investigate the effects and mechanisms of microRNA-140-5p (miR-140-5p) on myocardial ischemia-reperfusion injury (IRI). MATERIALS AND METHODS: We made the myocardial IRI model in rats and detected the expression of miR-140-5p. Anta-miR-140-5p was administered intravenously in the tail of rats. Then, we used 2, 3, 5-triphenyl tetrazolium chloride staining, cardiac function test, and histological experiment to observe the changes in myocardial infarct size, cardiac function, and cardiomyocyte apoptosis in rats. In in vitro experiments, we induced the damage of H9c2 cells by hypoxia/reoxygenation (H/R) model and detected the effects of miR-140-5p on the proliferation ability and apoptosis level of H9c2 cells. TargetScan database was used to predict the binding target of miR-140-5p and we verified the effect of miR-140-5p on the target through Dual-Luciferase reporter assay. RESULTS: MiR-140-5p is highly expressed in myocardial tissue of IRI rats and anta-miR-140-5p can reduce myocardial infarct area, improve cardiac function, and reduce the rate of myocardial cells apoptosis in rats. The expression of miR-140-5p in H/R-induced H9c2 cells was higher than that in the control group. MiR-140-5p inhibitor was found to promote the proliferation and decrease the apoptosis level of H9c2 cells, while miR-140-5p mimic was the opposite. The TargetScan system predicts the presence of binding sites for miR-140-5p and B-cell lymphoma-2 like 1 (BCL2L1). The Dual-Luciferase reporter assay found that miR-140-5p can bind to BCL2L1 and promote its degradation. In addition, the inhibition of BCL2L1 was found to promote apoptosis in H9c2 cells. CONCLUSIONS: In myocardial IRI, miR-140-5p targets BCL2L1 and promotes its degradation, thereby inducing myocardial apoptosis.

MiR-155 promotes proliferation and inhibits apoptosis of nasopharyngeal carcinoma cells through targeting PTEN-PI3K/AKT pathway.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a polygenic hereditary disease, and the exact pathogenesis remains poorly understood. MiR-155 regulates the development and progression of several tumors. However, the role of MiR-155 in NPC has not been elucidated. PATIENTS AND METHODS: The NPC cell line CNE2 was cultured in vitro and divided into control group, miR-155 mimics group, and miR-155 inhibitor group, followed by analysis of miR-155 expression by real-time PCR, cell proliferation by MTT assay, cell invasion by transwell chamber, Caspase3 activity, apoptosis of CNE2 cells by flow cytometry, and the expression of PTEN-PI3K/AKT signaling pathway by Western blot. RESULTS: Transfection of miR-155 mimics significantly up-regulated miR-155 expression, promoted the proliferation and invasion of CNE2 cells, inhibited Caspase 3 activity, and decreased cell apoptosis, and PTEN expression, as well as increased PI3K/AKT phosphorylation, compared with control group (p < 0.05). Transfection of miR-155 inhibitor inhibited the proliferation and invasion of CNE2 cells, increased Caspase 3 activity, cell apoptosis, and PTEN expression, as well as reduced PI3K/AKT phosphorylation. Compared with control group, the differences were statistically significant (p < 0.05). CONCLUSIONS: Up-regulation of miR-155 can promote the proliferation of NPC cells and inhibit cell apoptosis by targeting the PTEN-PI3K/AKT pathway, thereby participating in the development and invasion of NPC, indicating that it might be a potential novel target for treating NPC.

Identification of multiple genes and their expression profiles in four strains of Oreochromis spp. in response to Streptococcus iniae.

Two subtractive complementary DNA libraries were constructed from Nile tilapia Oreochromis niloticus vaccinated with formalin-killed Streptococcus iniae cells, and a further two constructed from O. niloticus infected with S. iniae. Of the 68 distinct expressed sequence tag (EST) contigs and singletons, 45 and 13 EST shared high similarities with genes of known and unknown functions, respectively. Ten EST contigs and singletons had no significant similarity to any sequences. Five putative immune-relevant genes, ß2m, α-ha, mmp9, pgrn and cxcr4, were selected for quantitative reverse-transcription polymerase chain reaction in four strains of Oreochromis spp.: genetically improved farmed tilapia (O. niloticus), Oreochromis aureus, O. niloticus and O. niloticus×O. aureus, with different disease resistance following infection with S. iniae. pgrn was up-regulated more significantly in disease-resistant strains than in the susceptible. α-ha was markedly down-regulated, and no significant differences in the expression level of ß2m were detected. A negative correlation was observed between the expression of mmp9 and that of cxcr4. The results provide insight into the molecular response of O. niloticus to S. iniae infection.

Pharmacokinetics of dl-praeruptorin A after single-dose intravenous administration to rats with liver cirrhosis.

BACKGROUND AND THE PURPOSE OF THE STUDY: As a novel drug in the treatment of cardiac diseases, dl-praeruptorin A (Pd-Ia) is the major active component of traditional herbal medicine Peucedanum praeruptorum Dunn and is metabolized primarily via cytochrome P450 isozymes (CYP) 3A1 and 3A2 in rats. In the present study, the influence of liver cirrhosis on pharmacokinetics of Pd-Ia and hepatic mRNA expression of CYP3A1 and 3A2 in rats with experimental liver cirrhosis (LC rats) were evaluated. METHODS: Pd-Ia was given intravenously (5 mg kg(-1)) to LC rats induced by dimethylnitrosamine and pharmacokinetic variables were measured. Enzyme kinetic metabolism of Pd-Ia in rat hepatic microsomes was also investigated and hepatic mRNA expression of CYP3A1 and 3A2 were measured by real-time PCR. RESULTS AND MAJOR CONCLUSION: After intravenous administration in LC rats, the area under the plasma concentration-time curve from time zero to infinity (AUC0-8) was significantly greater than that in control rats, which might be due to slower rate of the hepatic blood flow and significant slower hepatic intrinsic clearance (CL(int)) in rats. The decreased metabolic clearance of Pd-Ia in LC rats might be at least partly caused by the decreased levels of CYP3A1 and 3A2 responsible for Pd-Ia metabolism. These findings may provide new insights into the inter- and intra-individual pharmacokinetic variability of Pd-Ia.

Reducing the burden of road traffic injury: translating high-income country interventions to middle-income and low-income countries.

OBJECTIVE: To increase seat belt restraint use in Guangzhou City, People's Republic of China. DESIGN: Comparison group pre-test, post-test design. SETTING: Guangzhou City. INTERVENTIONS: Interventions to increase the prevalence of seat belt use in high-income countries (enhanced training and enforcement practices along with raising of public awareness) were adapted and implemented in Guangzhou. The prevalence of seat belt use was determined before and after the introduction of the 12-month intervention. Seat belt prevalence was also examined over the same time period in the neighboring city of Nanning, and an incremental cost-effectiveness analysis of the intervention was undertaken. MAIN OUTCOME MEASURES: Prevalence rates and incremental cost effectiveness ratios. RESULTS: A 12% increase in seat belt use was observed in Guangzhou over the study period, increasing from a prevalence of 50% before (error range 30-62%) to 62% after (error range 60-67%) (p<0.001) the intervention; an absolute change difference between the intervention and reference city of 20% was achieved. The incremental cost-effectiveness ratio of the intervention was yen 3246 (US dollars 418) per disability-adjusted life year saved. CONCLUSIONS: This city-wide intervention demonstrates that it is possible to increase the prevalence of seat belt use using similar methods to those used in high-income countries and, importantly, that such an approach is cost-effective.

Nickel-catalyzed

Oxabenzonorbornadienes 1 and 2 and azabenzonorbornadiene 3 undergo [2+2] cycloaddition with alkynes (PhC triple bond Ph, PhC triple bond CMe, PhC triple bond CCO2Et, PhC triple bond CCH(OEt)2, and HC triple bond C(CH2)4Me) in the presence of [Ni(PPh3)2Cl2], PPh3, and Zn powder in toluene to afford the corresponding exo-cyclobutene derivatives 4a-e, 5a-e, and 6 in fair to excellent yields. Under similar conditions. EtCO2C triple bond CCO2Et does not react with 1 in toluene to give the [2+2] cycloaddition product, but in acetonitrile, the catalytic [2+2] cycloaddition proceeds and cycloadduct 4 f is isolated in 83% yield. At high temperature, these cyclobutene derivatives readily undergo ring expansion to yield the corresponding 8-membered carbocyclic dienes. Thus, flash vacuum pyrolysis of 4a, 4d, 4f, 6, and 14 at 500 degrees C affords dienes 13a-d and 15 in 70-96% yields. This interesting ring expansion may be viewed as the insertion of an alkyne moiety into the carbon-carbon double bond of a cyclic olefin resulting in the enlargement of the ring by two carbons. Compound 13a is readily deoxygenated by TiCl4 and Zn in THF to give a cyclooctatetraene derivative 16 in 89% yield.