Yang Yu

Abstract Acute myocardial infarction (MI) is the leading cause of sudden death worldwide. MicroRNAs (miRs) is a novel class of regulators of cardiovascular diseases such as MI. This study aimed to explore the role of miR-98 in MI and its underlying mechanisms. We found that miR-98 was downregulated both in infarcted and ischemic myocardium of MI mice as well as H 2 O 2 -treated neonatal rat ventricular myocytes (NRVCs). miR-98 overexpression remarkably increased cell viability and inhibited apoptosis of H 2 O 2 -treated NRVCs. Meanwhile, overexpression of miR-98 reversed H 2 O 2 -induced Bcl-2 downregulation and Bax elevation and significantly reduced JC-1 monomeric cells. Meanwhile, miR-98 overexpression attenuated the upregulation of Fas and caspase-3 in H 2 O 2 -treated cardiomyocytes at the mRNA and protein levels. Dual-luciferase reporter assay showed that miR-98 directly targeted to Fas 3′-UTR. Furthermore, MI mice injected with miR-98-agomir had a significant reduction of apoptotic cells, the serum LDH levels, myocardial caspase-3 activity, Fas and caspase-3 expression in heart tissues. Administration of miR-98-agomir also showed decreased infarct size and improved cardiac function. Collectively, miR-98 is downregulated in the MI heart and NRVCs in response to H 2 O 2 stress, and miR-98 overexpression protects cardiomyocytes against apoptosis. Anti-apoptotic effects of miR-98 are associated with regulation of Fas/Caspase-3 apoptotic signal pathway.

In the realm of genetically transformed crops, the process of plant regeneration holds utmost significance. However, the low regeneration efficiency of several wheat varieties currently restricts the use of genetic transformation for gene functional analysis and improved crop production. This research explores overexpression of TaLAX PANICLE1 (TaLAX1), which markedly enhances regeneration efficiency, thereby boosting genetic transformation and genome editing in wheat. Particularly noteworthy is the substantial increase in regeneration efficiency of common wheat varieties previously regarded as recalcitrant to genetic transformation. Our study shows that increased expression of TaGROWTH-REGULATING FACTOR (TaGRF) genes, alongside that of their co-factor, TaGRF-INTERACTING FACTOR 1 (TaGIF1), enhances cytokinin accumulation and auxin response, which may play pivotal roles in the improved regeneration and transformation of TaLAX1-overexpressing wheat plants. Overexpression of TaLAX1 homologs also significantly increases the regeneration efficiency of maize and soybean, suggesting that both monocot and dicot crops can benefit from this enhancement. Our findings shed light on a gene that enhances wheat genetic transformation and elucidate molecular mechanisms that potentially underlie wheat regeneration.

PURPOSE: The need of prophylactic central neck dissection (PCND) in patients with papillary thyroid carcinoma (PTC) is still controversial. The major restriction of PCND is the potential complications. We undertook a retrospective study to discuss its necessity in PTC patients. METHODS: A total of 188 patients with PTC who underwent total thyroidectomy and PCND were involved. In all of these, central lymph nodes were pathologic examined. Univariate and multivariate analyses were performed based on tumor location and size, etc. RESULTS: Overall, node metastases were found in 44.1 % (83/188) of patients. Tumor size was the independent positive predictor for lymph node metastasis, while gender, age, tumor multifocality, tumor location, and capsular infiltration were not independent predictors of central lymph node metastases. Postoperative complications happened in 5.3 % (10/188) of patients, which 4.8 % (9/188) had temporary hypocalcemia and 0 % (0/188) had permanent hypocalcemia. Rates of temporary and permanent recurrent laryngeal nerve injury were 0.5 % (1/188) and 0 % (0/188), respectively. CONCLUSIONS: PCND is recommended in all patients with PTC.

BACKGROUND/AIMS: MicroRNAs play an important role in regulating myocardial infarction (MI)-induced cardiac injury. MicroRNA-124 (miR-124) plays a vital role in regulating cellular proliferation, differentiation and apoptosis. Although the alteration of miR-124 was confirmed in peripheral blood of MI patients, little is known regarding the biological functions of miR-124 in cardiomyocytes. This study was designed to explore the role of miR-124 in MI and its underlying mechanisms. METHODS: Real-time PCR was used to quantify the microRNAs levels. TUNEL and Flow cytometry were performed to measure cell apoptosis. Western blot analysis was employed to detect expression of Bcl-2, Bax, Caspase-3 and STAT3 proteins. RESULTS: We revealed that miR-124 was significantly up-regulated in a mice model of MI and in neonatal rat ventricular myocytes (NRVMs) with H2O2 treatment. H2O2 treatment induced cardiomyocyte injury with reduced cell viability and enhanced apoptotic cell death, whereas silencing expression of miR-124 by AMO-124 (antisense inhibitor oligodeoxyribonucleotides) alleviated these deleterious changes. AMO-124 decreased the expression of Bax and cleaved-caspase-3 and upregulated the expression of Bcl-2 in H2O2-treated NRVMs. Besides, AMO-124 improved mitochondrial dysfunction of NRVMs induced by H2O2 treatment. Moreover, antagomir-124 markedly decreased the infarct area and apoptotic cardiomyocytes and improved cardiac function in MI mice. Furthermore, we identified STAT3 as a direct target of miR-124, and downregulation of miR-124 ameliorated the diminished levels of STAT3 and p-STAT3 (Tyr705) in response to H2O2 or MI. STAT3 inhibitor, stattic, was shown to attenuate the elevation of p-STAT3 in NRVMs with AMO-124 transfection. Inhibiting of STAT3 activity by stattic abrogated protective effects of AMO-124 on H2O2-induced cardiomyocytes apoptosis. CONCLUSION: Taken together, our data demonstrate that downregulation of miR-124 inhibits MI-induced apoptosis through upregulating STAT3, which suggests the therapeutic potential of miR-124 for myocardial infarction.