MicroRNA397 promotes rice flowering by regulating the photorespiration pathway.

The precise timing of flowering plays a pivotal role in ensuring successful plant reproduction and seed production. This process is intricately governed by complex genetic networks that integrate internal and external signals. This study delved into the regulatory function of microRNA397 (miR397) and its target gene LACCASE-15 (OsLAC15) in modulating flowering traits in rice (Oryza sativa). Overexpression of miR397 led to earlier heading dates, decreased number of leaves on the main stem, and accelerated differentiation of the spikelet meristem. Conversely, overexpression of OsLAC15 resulted in delayed flowering and prolonged vegetative growth. Through biochemical and physiological assays, we uncovered that miR397-OsLAC15 had a profound impact on carbohydrate accumulation and photosynthetic assimilation, consequently enhancing the photosynthetic intensity in miR397-overexpressing rice plants. Notably, we identified that OsLAC15 is at least partially localized within the peroxisome organelle, where it regulates the photorespiration pathway. Moreover, we observed that a high CO2 concentration could rescue the late flowering phenotype in OsLAC15-overexpressing plants. These findings shed valuable insights into the regulatory mechanisms of miR397-OsLAC15 in rice flowering and provided potential strategies for developing crop varieties with early flowering and high-yield traits through genetic breeding.

Big endothelin-1 level is a useful marker for predicting the presence of isolated coronary artery ectasia.

CONTEXT: Endothelin-1(ET-1) has been implicated in coronary artery disease (CAD) and may be associated with coronary artery ectasia (CAE). OBJECTIVE: To clarify the relationship between big ET-1 and isolated CAE. METHODS: We measured big ET-1 with ELISA in 216 patients (CAE, n = 72; CAD, n = 72; normal, n = 72) and evaluated the link with isolated CAE. RESULTS: The level of plasma big ET-1 was significantly higher in patients with isolated CAE (p < 0.001). Big ET-1 was strongly and independently associated with CAE by multivariate analysis (OR 95%CI: 1.026 (1.018-1.034), p = 0.000). CONCLUSIONS: Big ET-1 may be a useful predictor for the presence of isolated CAE.

Prognostic Value of Coronary Artery Stenoses, Markis Class, and Ectasia Ratio in Patients with Coronary Artery Ectasia.

OBJECTIVES: To assess the prognostic value of coexisting coronary artery disease (CAD), Markis class, and ectasia ratio for major adverse cardiovascular events in patients with coronary artery ectasia (CAE). METHODS: A total of 512 consecutive patients with angiographically proven CAE were enrolled. Coronary ectasia extent was graded using the Markis class, and ectasia severity was assessed based on the ectasia ratio. Patients were followed up for a median of 34.6 months. RESULTS: In the current study, 76 cases had isolated CAE, while the remaining 436 cases had coexisting CAD (mixture CAE). Males (84.4%) were predominantly affected, and the right coronary artery (55.1%) was most commonly involved. During follow-up, 86 overall major adverse cardiovascular events were diagnosed. Kaplan-Meier analysis failed to reveal any differences between isolated and mixture CAE in both cumulative and event-free survival analyses (p=0.429 and p=0.277, respectively). Moreover, when patients were divided into 4 groups according to Markis class (type I-IV) or 2 groups based on the ectasia ratio (1.5-2.0 and >2.0), there was no significant difference in survival outcomes among the groups (p>0.05). CONCLUSIONS: In this follow-up study with a relatively large sample, the survival rate of patients with CAE appeared to be independent of coexisting CAD and ectasia extent and severity.

Association of alkaline phosphatase with isolated coronary artery ectasia.

BACKGROUND: It has been shown that alkaline phosphatase (ALP) is a reliable marker for cardiovascular events and mortality. However, there is no data available regarding the association of ALP with isolated coronary artery ectasia (CAE). The aim of the present study was to assess the serum ALP activity in isolated CAE. METHODS: Seventy-nine patients with isolated CAE (59 males; mean age, 52 ± 12 years) and 88 age- and gender-matched normal subjects (73 males; mean age, 52 ± 7 years) were enrolled. Baseline characteristics were recorded in both groups and serum ALP activity were compared between the two groups. RESULTS: Patients with angiography-proved isolated CAE had significantly higher serum ALP activity compared with angiographic normal controls (72.41 ± 29.97 vs. 59.27 ± 14.46, p < 0.001). In the multivariate analysis, increased ALP (OR = 1.037, 95% CI 1.017-1.057, p < 0.001) were independent predictors for the presence of isolated CAE. A cut-off of ≥ 66.5 U/L of ALP activity measured on admission had a 60.8% sensitivity and 75.0% specificity in predicting isolated CAE by receiver operating characteristic (ROC) curve analysis. CONCLUSION: Our data firstly demonstrated that serum ALP activity, a readily available clinical laboratory value, was associated with the presence of isolated CAE.

Efficacy and safety of drug-coated balloon for de novo lesions of large coronary arteries: Systematic review and meta-analysis of randomized controlled trials.

Background: Drug-coated balloon (DCB) is a novel approach to avoiding stent-related complications and has proven effective for the treatment of in-stent restenosis (ISR) and small vessels. However, its role in the treatment of de novo lesions in large vessels is less settled. Aims: To estimate the efficacy and safety of drug-coated balloon versus stent in the treatment of de novo lesions in large coronary arteries. Methods: We searched the literature until April 2023. We judged the safety of DCB based on major adverse cardiovascular events (MACEs), cardiac death, all-cause mortality, non-fatal myocardial infarction, target lesion revascularization (TLR), and bleeding event; and efficacy according to late lumen loss (LLL), minimum lumen diameter (MLD). We conducted subgroup analyses according to stent type and whether urgent PCI was required. Results: A total of 10 RCTs were included. Overall, LLL (mean difference (MD) = -0.19, 95 % confidence interval (CI): -0.32 to -0.06, P = 0.003) was lower in the DCB group than in the Stent arm. This effect was consistent in subgroup analysis regardless of stent type and disease type. In terms of safety indicators, there were no significant differences between DCB and stent. The subgroup analyses found that safety indicators showed no significant differences between DCB and drug-eluting stent (DES), but TLR was lower in the DCB than in the bare metal stent (BMS). Moreover, in ST-elevation myocardial infarction (STEMI), safety indicators and LLL showed no significant differences between DCB and DES, but MLD in the DCB was smaller. While in patients with excluded STEMI, MACE and TLR was lower in the DCB compared with the overall stent. Conclusions: DCB could be a promising alternative for treating de novo lesions in large coronary arteries with satisfactory efficacy and low risk, superior to BMS and not inferior to DES, with a trend toward lower late lumen loss.

GateView: A Multi-Omics Platform for Gene Feature Analysis of Virus Receptors within Human Normal Tissues and Tumors.

Viruses are obligate intracellular parasites that rely on cell surface receptor molecules to complete the first step of invading host cells. The experimental method for virus receptor screening is time-consuming, and receptor molecules have been identified for less than half of known viruses. This study collected known human viruses and their receptor molecules. Through bioinformatics analysis, common characteristics of virus receptor molecules (including sequence, expression, mutation, etc.) were obtained to study why these membrane proteins are more likely to become virus receptors. An in-depth analysis of the cataloged virus receptors revealed several noteworthy findings. Compared to other membrane proteins, human virus receptors generally exhibited higher expression levels and lower sequence conservation. These receptors were found in multiple tissues, with certain tissues and cell types displaying significantly higher expression levels. While most receptor molecules showed noticeable age-related variations in expression across different tissues, only a limited number of them exhibited gender-related differences in specific tissues. Interestingly, in contrast to normal tissues, virus receptors showed significant dysregulation in various types of tumors, particularly those associated with dsRNA and retrovirus receptors. Finally, GateView, a multi-omics platform, was established to analyze the gene features of virus receptors in human normal tissues and tumors. Serving as a valuable resource, it enables the exploration of common patterns among virus receptors and the investigation of virus tropism across different tissues, population preferences, virus pathogenicity, and oncolytic virus mechanisms.

Antithrombotic effect of a polysaccharide fraction from Laminaria japonica from the South China Sea.

Some in vitro studies have identified an antithrombotic effect of polysaccharides from Laminaria japonica, but this activity remains to be confirmed in vivo. In this study a polysaccharide fraction termed PLG was extracted from L. japonica in the Beibu Gulf in Guangxi, China, and its antithrombotic effects explored in rat models of carotid and venous thrombosis. Its anticoagulation and antiplatelet properties were assessed by measuring the prothrombin time (PT), activated partial thromboplastin time (APTT) and ADP-induced platelet aggregation rate (Agg(max)). Its effects on bleeding time were measured using the tail transection method. It was found that pretreatment with an intraperitoneal injection of PLG at 2.5 or 5.0 mg/kg significantly prolonged the occlusion time in the carotid thrombosis model, and a dose of 5.0 mg/kg reduced the thrombus weight in the venous thrombosis model. Pretreatment with PLG (5.0 mg/kg) increased the APTT and decreased the ADP-induced platelet Agg(max). Neither dose of PLG significantly prolonged the bleeding time compared with the control group. In an in vitro anticoagulation assay using human plasma, PLG at 57.14, 28.57 and 28.57 µg/mL inhibited APTT and PT in a concentration-dependent manner. The results show that PLG possesses antithrombotic activity in a rat model, and that it may prove to be clinically useful in humans.

PERK Signaling Controls Myoblast Differentiation by Regulating MicroRNA Networks.

The unfolded protein response (UPR) plays important roles in various cells that have a high demand for protein folding, which are involved in the process of cell differentiation and development. Here, we separately knocked down the three sensors of the UPR in myoblasts and found that PERK knockdown led to a marked transformation in myoblasts from a fusiform to a rounded morphology, which suggests that PERK is required for early myoblast differentiation. Interestingly, knocking down PERK induced reprogramming of C2C12 myoblasts into stem-like cells by altering the miRNA networks associated with differentiation and stemness maintenance, and the PERK-ATF4 signaling pathway transactivated muscle differentiation-associated miRNAs in the early stage of myoblast differentiation. Furthermore, we identified Ppp1cc as a direct target gene of miR-128 regulated by the PERK signaling pathway and showed that its repression is critical for a feedback loop that regulates the activity of UPR-associated signaling pathways, leading to cell migration, cell fusion, endoplasmic reticulum expansion, and myotube formation during myoblast differentiation. Subsequently, we found that the RNA-binding protein ARPP21, encoded by the host gene of miR-128-2, antagonized miR-128 activity by competing with it to bind to the 3' untranslated region (UTR) of Ppp1cc to maintain the balance of the differentiation state. Together, these results reveal the crucial role of PERK signaling in myoblast maintenance and differentiation and identify the mechanism underlying the role of UPR signaling as a major regulator of miRNA networks during early differentiation of myoblasts.

Relation of diabetes to coronary artery ectasia: A meta-analysis study.

OBJECTIVE: Previous studies have shown a significant negative association between diabetes and abdominal aortic aneurysm. However, the relation of diabetes to coronary artery ectasia (CAE) has not well established. The aim of the current study was to conduct a systemic review for evaluating the relationship between diabetes and CAE. METHODS: A systemic search of electronic databases (PUBMED, EMBASE, OVID, WEB OF SCIENCE, THE COCHRANCE LIBRARY) from 1970 to March 2013 was performed. Additionally, checking reference lists from identified articles, reviews, and the abstracts presented at related scientific meetings were also carried out. All case-control studies investigating appropriate prevalence data were included. RESULTS: Among 328 articles, 10 case-control studies were finally identified. The prevalence of diabetes in studied patients with CAE was 8% to 33%, while in those without CAE was ranged from 13.5% to 35%. Pooled analysis showed a reduced rate of diabetes amongst patients with CAE compared to those without (OR 0.65, 0.54-0.77, p<0.0001). CONCLUSION: Our findings suggested that diabetes might play a protective role for the development of CAE, indicating that further study is needed to evaluate the association diabetes and CAE including underlying mechanisms and future medical interventional strategies.

Clinical features of coronary artery ectasia in the elderly.

OBJECTIVE: To investigate the incidence, imaging and clinical characteristics in elderly patients with coronary artery ectasia (CAE). METHODS: A retrospective analysis was conducted on patients with CAE who underwent coronary angiography between January 2006 and December 2012. According to age, the enrolled patients were divided into two groups (elderly group, age ≥ 65 years; non-elderly group, age < 65 years). The clinical feature, imaging characteristics and the 5-year survival rate of the two groups were compared. RESULTS: The prevalence of CAE in elderly patients was 0.33%. Patients in elderly group were found to have significantly higher proportion of female (30.1% vs. 10.1%, P < 0.001), three-vessel disease (60.5% vs. 45.2%, P = 0.003) and localized ectasia (55.0% vs. 40.2%, P = 0.003). In addition, body mass index (20.90 ± 2.71 kg/m(2) vs. 22.31 ± 2.98 kg/m(2), P < 0.001) and percentage of current smokers (45.0% vs. 64.6%, P < 0.001) were significantly lower in elderly group. Cumulative survival curves demonstrated reduced 5-year cumulative survival at the follow-up in the elderly group compared with the non-elderly group (88.0% vs. 96.0%, P = 0.002). But the 5-year event free survival rate failed to show a significant difference between the two groups (31.0% vs. 35.0%, P = 0.311). CONCLUSION: The prevalence of CAE in elderly patients was 0.33%, which was about 1/3 of the entire numbers of CAE patients. There were significant differences between the elderly and the non-elderly patients with CAE in terms of coronary artery disease risk factors and coronary artery ectatic characteristics. CAE might be associated with increased mortality risk in the elderly.

MicroRNA-195 plays a tumor-suppressor role in human glioblastoma cells by targeting signaling pathways involved in cellular proliferation and invasion.

Accumulating evidence has implicated the deregluation of miRNAs in tumorigenesis. Previous studies have reported that microRNA-195 (miR-195) is markedly down-regulated in human glioblastoma cells, compared with normal brain tissue, but the biological role of miR-195 in glioblastoma development is currently unknown. In this study, we define a tumor-suppressor role for miR-195 in human glioblastoma cells. Over-expression of miR-195 in glioblastoma cell lines robustly arrested cell cycle progression and significantly repressed cellular invasion. We identified E2F3 and CCND3 as functional downstream targets of miR-195 in glioblastoma cells. Through knockdown studies, we demonstrated that E2F3 was the dominant effector of miR-195-mediated cell cycle arrest and that CCND3 was a key mediator of miR-195-induced inhibition of glioblastoma cell invasion. Furthermore, we showed that p27(Kip1) was an important regulator downstream of CCND3 and that the accumulation of p27(Kip1) in the cytoplasm might be responsible for the miR-195-mediated cell invasion inhibition in glioblastoma cells. This work provides evidence for the initial mechanism by which miR-195 negatively regulates both the proliferation and invasion of glioblastoma cells, suggesting that the down-regulation of miR-195 might contribute to the malignant transformation of glioblastoma cells and could be a molecular signature associated with glioblastoma progression.

Triggering Fbw7-mediated proteasomal degradation of c-Myc by oridonin induces cell growth inhibition and apoptosis.

The transcription factor c-Myc is important in cell fate decisions and is frequently overexpressed in cancer cells, making it an attractive therapeutic target. Natural compounds are among the current strategies aimed at targeting c-Myc, but their modes of action still need to be characterized. To explore the mechanisms underlying the anticancer activity of a natural diterpenoid, oridonin, we conducted miRNA expression profiling and statistical analyses that strongly suggested that c-Myc was a potential molecular target of oridonin. Furthermore, experimental data showed that oridonin significantly reduced c-Myc protein levels in vitro and in vivo and that this reduction was mediated by the ubiquitin-proteasome system. Fbw7, a component of the ubiquitin-proteasome system and an E3 ubiquitin ligase of c-Myc, was upregulated rapidly in K562 cells and other leukemia and lymphoma cells, resulting in the rapid turnover of c-Myc. In cell lines harboring mutations in the WD domain of Fbw7, the degradation of c-Myc induced by oridonin was attenuated during short-term treatment. GSK-3, an Fbw7 priming kinase, was also activated by oridonin, along with an increase in T58-phosphorylated c-Myc. Furthermore, the knockdown of Fbw7 or the forced expression of stable c-Myc resulted in reduced sensitization to oridonin-induced apoptosis. Our observations help to clarify the anticancer mechanisms of oridonin and shed light on the application of this natural compound as an Fbw7-c-Myc pathway targeting agent in cancer treatment.

Expression analysis of phytohormone-regulated microRNAs in rice, implying their regulation roles in plant hormone signaling.

Twenty-two conserved miRNAs were chosen to investigate the expression pattern in response to phytohormone treatments, in which the effects of five classic plant hormone stresses were surveyed in Oryza sativa. The results showed that 11 miRNAs were found to be dysregulated by one or more phytohormone treatments. The target genes of these miRNAs were validated in vivo and their expression profiling were revealed. We also analyzed the promoter regions of the 22 conserved miRNAs for phytohormone-responsive elements and the existence of the elements provided further evidences supporting our results. These findings enable us to further investigate the role of miRNAs in phytohormone signaling.