RETINOBLASTOMA RELATED 1 switches mitosis to meiosis in rice.

The transition from mitosis to meiosis is a critical event in the reproductive development of all sexually reproducing species. However, the mechanisms that regulate this process in plants remain largely unknown. Here, we find that the rice (Oryza sativa L.) protein RETINOBLASTOMA RELATED 1 (RBR1) is essential to the transition from mitosis to meiosis. Loss of RBR1 function results in hyper-proliferative sporogenous-cell-like cells (SCLs) in the anther locules during early stages of reproductive development. These hyper-proliferative SCLs are unable to initiate meiosis, eventually stagnating and degrading at late developmental stages to form pollen-free anthers. These results suggest that RBR1 acts as a gatekeeper of entry into meiosis. Furthermore, cytokinin content is significantly increased in rbr1 mutants, whereas the expression of type-B response factors, particularly LEPTO1, is significantly reduced. Given the known close association of cytokinins with cell proliferation, these findings imply that hyper-proliferative germ cells in the anther locules may be attributed to elevated cytokinin concentrations and disruptions in the cytokinin pathway. Using a genetic strategy, the association between germ cell hyper-proliferation and disturbed cytokinin signaling in rbr1 has been confirmed. In summary, we reveal a unique role of RBR1 in the initiation of meiosis; our results clearly demonstrate that the RBR1 regulatory module is connected to the cytokinin signaling pathway and switches mitosis to meiosis in rice.

Retrograde type A aortic dissection during or after thoracic endovascular aortic repair: a single center 16-year experience.

Objective: This article aims to investigate the incidence rate of retrograde type A aortic dissection (RTAD) and the risk factors of RTAD in relation to thoracic endovascular aortic repair (TEVAR). Methods: Patients with thoracic aortic disease who underwent TEVAR at Henan Provincial People's Hospital from January 2004 to December 2019 were enrolled in the present research. The risk factors associated with RTAD following TEVAR using univariate and multiple logistic regression analyses. Results: During the study period, A total of 1,688 TEVAR patients were included in this study, and of these, 1,592 cases were included in the type B aortic dissection (TBAD) group, and 96 cases were included in the non-TBAD group. There were 1,230 cases of aortic dissection and 362 cases of aortic intramural hematoma and/or penetrating ulcer in the TBAD group. The non-TBAD group included 68 cases of thoracic aortic aneurysm, 21 cases of thoracic aortic pseudoaneurysm, and seven cases of congenital aortic coarctation. The overall incidence rate of RTAD was 1.1% (18/1,688) in patients, all of which occurred in the TBAD group. The cohort comprised 18 RTAD patients with an average age of 56.78, consisting of 13 males and 5 females. Among them, 13 individuals exhibited hypertension. Ten instances happened within the TEVAR perioperative period, including two cases during the surgery, six cases occurred within three months, two cases occurred after one year, and the longest interval was 72 months following TEVAR. TEVAR was successfully implemented in 17 patients, while the operation technique was temporarily altered in one case. The new entry position for RTAD was identified as the proximal region of the stent graft (SG) in 13 patients, while in five cases, the entry site was more than 2 cm away from the proximal region of the SG. 17 cases were at the greater curvature of the aorta, and one case was at the lesser curvature. Multivariate logistic regression analysis revealed that the SG oversizing ratio is a relevant risk factor for RTAD. However, ascending aortic diameter, aortic arch type, SG type, and anchored region were not directly related to the occurrence of RTAD. Conclusion: RTAD is a rare yet catastrophic complication. It could occur both during the procedure, early and late postoperative periods. Maintaining an appropriate SG oversizing ratio is crucial to minimize the risk of RTAD.

Transversalis fascia suture reinforcement may facilitate the performance of electrospun P(LLA-CL) nanoscale fibrinogen mesh in inguinal hernia repair: a prospective single-center cohort study.

The aim of this study was to evaluate a new electrospun P(LLA-CL) nanoscale fibrinogen mesh performance in real-world clinical practice. A prospective, single-center evaluation of Lichtenstein inguinal hernia repair using electrospun P(LLA-CL) nanoscale fibrinogen mesh in elderly patients with comorbid diseases was conducted between 2020 and 2022. A suture reinforcement of transversalis fascia was applied before mesh implantation. Hernia recurrence, pain score and overall complication rate were measured. A total of 52 inguinal hernias in 48 patients were included. The age of patients ranged from 33 to 95 years, with a median of 78 years. Comorbid conditions included cardiopulmonary disease, organ dysfunction, anticoagulant use, diabetes and smoking. By optimizing the physical condition perioperatively, all patients finished treatment successfully. Four cases recurred secondary to direct hernias or combined hernias and were diagnosed in the first 24 case cohort during follow-up. With surgical procedural modification involving strengthening the posterior inguinal floor by reef-up suturing of the transversalis fascia and the inferior edge of mesh slit to accommodate the spermatic cord, no further recurrence was diagnosed. Postoperative pain was mild and the pain score decreased three months after surgery compared to 1 week after surgery (p = 0.0099). No severe complications occurred, while seroma occurred in six cases. Electrospun P(LLA-CL) nanoscale fibrinogen mesh is safe and effective in repairing inguinal hernias in elderly patients with comorbid disease. A strengthening of the transversalis fascia by suturing may enhance the performance of this mesh.

Sorafenib promotes hepatocellular carcinoma invasion via interleukin-6/HIF-1α/PFKFB3.

Background: Although sorafenib is adopted as the first-line treatment for unresectable liver cancer, the antitumor efficacy is severely limited by the pro-invasive side effect. Methods: To explore the underlying mechanisms, various-dosage sorafenib was applied to survey its effect on cell invasion in HCCLM3 and PLC cell models. Results: Our results revealed that high-dosage sorafenib inhibited liver cancer cell invasion. By contrast, sorafenib with low and median dosages promoted the invasion. In vivo studies showed that sorafenib with a median dosage increased the intrahepatic metastasis (IHM) and lung metastasis (LM) of liver cancer cells, while sorafenib with a high dosage inhibited IHM and LM. Then, bioinformatics analysis indicated that HIF-1α, IL-6, and PFKFB3 were associated with the sorafenib resistance. In vitro models showed that the pro-invasive effect was mediated by IL-6/HIF-1α/PFKFB3 regulation in dosage- and time-dependent manners. PFKFB3 knockdown confirmed that PFKFB3 promoted HCCLM3 cell migration via modulating EMT-related markers. Furthermore, we found that sorafenib upregulated PFKFB3 by IL-6/HIF-1α in a time-dependent manner, without direct effect on PFKFB3 expression. Conclusions: In summary, these results demonstrated that sorafenib could dose-dependently promote cell invasion, intrahepatic and lung metastasis in hepatocellular carcinoma through IL-6/HIF-1α mediated PFKFB3 activation, providing novel insights to improve the therapeutic efficacy of sorafenib.

RNA polymerase I subunit RPA43 activates rRNA expression and cell proliferation but inhibits cell migration.

The products synthesized by RNA polymerase I (Pol I) play fundamental roles in several cellular processes, including ribosomal biogenesis, protein synthesis, cell metabolism, and growth. Deregulation of Pol I products can cause various diseases such as ribosomopathies, leukaemia, and solid tumours. However, the detailed mechanism of Pol I-directed transcription remains elusive, and the roles of Pol I subunits in rRNA synthesis and cellular activities still need clarification. In this study, we found that RPA43 expression levels positively correlate with Pol I product accumulation and cell proliferation, indicating that RPA43 activates these processes. Unexpectedly, RPA43 depletion promoted HeLa cell migration, suggesting that RPA43 functions as a negative regulator in cell migration. Mechanistically, RPA43 positively modulates the recruitment of Pol I transcription machinery factors to the rDNA promoter by activating the transcription of the genes encoding Pol I transcription machinery factors. RPA43 inhibits cell migration by dampening the expression of c-JUN and Integrin. Collectively, we found that RPA43 plays opposite roles in cell proliferation and migration except for driving Pol I-dependent transcription. These findings provide novel insights into the regulatory mechanism of Pol I-mediated transcription and cell proliferation and a potential pathway to developing anti-cancer drugs using RPA43 as a target.

CRISPR-mediated technology for seed oil improvement in rapeseed: Challenges and future perspectives.

Rapeseed not only provide considerable amount of edible oil with high nutritional properties but can also be used as a raw material for biofuel production in many industries. It is therefore in high demand to bring genetic changes in order to fulfill the need of human and of industries. Though traditional breeding techniques such as hybridization and mutagenesis remained the top methods for long time to create improved varieties in oilseed rape. Clustered regularly interspaced short palindromic repeats (CRISPR) is becoming one of the most valuable gene editing technologies that allow precise genome engineering, and open new ways for research in plant functional genomics. Though CRISPR has been used in many other crops for genetic improvement it is expected to be an effective tool for genome editing and molecular design in oilseed rape for seed oil improvement. This mini review will discuss and summarize the past and ongoing research and development in rapeseed in terms of seed oil improvement and fatty acid composition using CRISPR technology. In addition, the factors that hinder the efficiency of this tool and how to eliminate those factors will be briefly summarized. The improvement of CRISPR technology for getting better results in oilseed rape will also be considered here. This minireview will open new windows for researchers in Brassica napus oil improvement research and genetic improvement using CRISPR technology.

Room-Temperature Optoelectronic Gas Sensor Based on Core-Shell g-C3N4@WO3 Heterocomposites for Efficient Ammonia Detection.

The ever-growing modern industry promotes the evolution of gas sensors for environmental monitoring and safety inspection. However, traditional chemiresistive gas sensors still suffer from drawbacks of high power consumption and detection limit, mainly due to the insufficient charge-transfer ability of gas-sensing materials. Here, an optoelectronic gas sensor that can detect ppb-level ammonia at room temperature is constructed based on core-shell g-C3N4@WO3 heterocomposites. The growth of WO3 nanosheets on graphitic g-C3N4 nanosheets was precisely controlled, achieving well-defined g-C3N4@WO3 core-shell architectures. Based on the synergism between light activation and the amplification effect of in situ-formed heterojunctions, the g-C3N4@WO3 sensor exhibits improved sensing characteristics for reliable ammonia detection. As compared with the pristine g-C3N4 sensor, the sensor response toward ammonia is enhanced 21 times and the detection limit is reduced from 308 to 108 ppb. This work provides a successful approach for the in situ formation of core-shell g-C3N4@WO3 interfacial composites and offers an easy solution for the rational design of advanced optoelectronic gas sensors.

Arabidopsis ABCG14 forms a homodimeric transporter for multiple cytokinins and mediates long-distance transport of isopentenyladenine-type cytokinins.

Cytokinins (CKs), primarily trans-zeatin (tZ) and isopentenyladenine (iP) types, play critical roles in plant growth, development, and various stress responses. Long-distance transport of tZ-type CKs meidated by Arabidopsis ATP-binding cassette transporter subfamily G14 (AtABCG14) has been well studied; however, less is known about the biochemical properties of AtABCG14 and its transporter activity toward iP-type CKs. Here we reveal the biochemical properties of AtABCG14 and provide evidence that it is also required for long-distance transport of iP-type CKs. AtABCG14 formed homodimers in human (Homo sapiens) HEK293T, tobacco (Nicotiana tabacum), and Arabidopsis cells. Transporter activity assays of AtABCG14 in Arabidopsis, tobacco, and yeast (Saccharomyces cerevisiae) showed that AtABCG14 may directly transport multiple CKs, including iP- and tZ-type species. AtABCG14 expression was induced by iP in a tZ-type CK-deficient double mutant (cypDM) of CYP735A1 and CYP735A2. The atabcg14 cypDM triple mutant exhibited stronger CK-deficiency phenotypes than cypDM. Hormone profiling, reciprocal grafting, and 2H6-iP isotope tracer experiments showed that root-to-shoot and shoot-to-root long-distance transport of iP-type CKs were suppressed in atabcg14 cypDM and atabcg14. These results suggest that AtABCG14 participates in three steps of the circular long-distance transport of iP-type CKs: xylem loading in the root for shootward transport, phloem unloading in the shoot for shoot distribution, and phloem unloading in the root for root distribution. We found that AtABCG14 displays transporter activity toward multiple CK species and revealed its versatile roles in circular long-distance transport of iP-type CKs. These findings provide new insights into the transport mechanisms of CKs and other plant hormones.

STAT3 and p63 in the Regulation of Cancer Stemness.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor with many important functions in normal and transformed cells. STAT3 regulatory activities are highly complex as they are involved in various signaling pathways in different cell types under different conditions. Biologically, STAT3 is a regulative factor for normal and cancer stem cells (CSCs). Tumor protein p63 (p63), a member of the p53 protein family, is involved in these biological processes and is also physically and functionally associated with STAT3. STAT3 activation occurs during various aspects of carcinogenesis, including regulation of CSCs properties. In combination with p63, STAT3 is a possible biological marker of CSCs and a major regulator of maintenance of stemness in CSCs. We summarized the STAT3 functions and regulation and its role in CSC properties and highlight how these are affected by its associations with p63.

Discrimination between raw and ginger juice processed Magnoliae officinalis cortex based on HPLC and Heracles NEO ultra-fast gas phase electronic nose.

INTRODUCTION: Magnoliae officinalis cortex (MOC), a traditional Chinese medicine, has been used in treating gastrointestinal diseases since ancient time. According to the Chinese Pharmacopoeia, it includes two kinds of decoction pieces, raw and ginger juice processed Magnoliae officinalis cortex (RMOC and GMOC). OBJECTIVE: The aim of this paper was to study the differences between non-volatile and volatile components in RMOC and GMOC. METHODS: The non-volatile components were detected by HPLC fingerprinting coupled with content determination (syringin, magnoflorine, honokiol and magnolol). Meanwhile, their odor information was obtained using a Heracles NEO ultra-fast gas phase electronic nose to conduct radar fingerprint analysis, principal component analysis and discriminant factor analysis, and the volatile components were analyzed qualitatively by the Kovats retention index and the AroChemBase database. RESULTS: The HPLC fingerprints were established and 20 common peaks were found in all chromatograms with similarity values of more than 0.900. The content determination results showed that the contents of syringin and magnoflorine decreased, while the contents of honokiol and magnolol increased in GMOC. By the gas phase electronic nose, the two decoction pieces could be distinguished obviously and 16 possible compounds were identified. Among them, the relative contents of (-)-α-pinene and ß-pinene increased, while ß-phellandrene and (+)-limonene levels decreased. CONCLUSION: The results suggested that honokiol, magnolol, (-)-α-pinene and ß-pinene might be the main substances which could enhance the harmonizing effect on the stomach. Moreover, this paper could lay a foundation for exploring the processing mechanism of MOC and provide a novel method for the research of other traditional Chinese medicine with strong aroma.

Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway.

RNA polymerase III (pol III) products play fundamental roles in a variety of cellular processes, including protein synthesis and cancer cell proliferation. In addition, dysregulation of pol III-directed transcription closely correlates with tumorigenesis. It is therefore of interest to identify novel pathways or factors governing pol III-directed transcription. Here, we show that transcription factor (TF) GATA binding protein 4 (GATA4) expression in SaOS2 cells was stimulated by the silencing of filamin A (FLNA), a repressor of pol III-directed transcription, suggesting that GATA4 is potentially associated with the regulation of pol III-directed transcription. Indeed, we show that GATA4 expression positively correlates with pol III-mediated transcription and tumor cell proliferation. Mechanistically, we found that GATA4 depletion inhibits the occupancies of the pol III transcription machinery factors at the loci of pol III target genes by reducing expression of both TFIIIB subunit TFIIB-related factor 1 and TFIIIC subunit general transcription factor 3C subunit 2 (GTF3C2). GATA4 has been shown to activate specificity factor 1 (Sp1) gene transcription by binding to the Sp1 gene promoter, and Sp1 has been confirmed to activate pol III gene transcription by directly binding to both Brf1 and Gtf3c2 gene promoters. Thus, the findings from this study suggest that GATA4 links FLNA and Sp1 signaling to form an FLNA/GATA4/Sp1 axis to modulate pol III-directed transcription and transformed cell proliferation. Taken together, these results provide novel insights into the regulatory mechanism of pol III-directed transcription.

[Protective effects of salidroside on vascular endothelial cells in rats with frostbite after chronic hypoxia].

Objective: To investigate the protective effects of salidroside on endothelial cells in rats with frostbite after chronic hypoxia. Methods: Healthy male SD rats, randomly divided into 3 groups with 10 rats in each group, which included the sham injury group, the model group, and the model +salidroside group. The rats in each group were placed in a composite low-pressure chamber to simulate a environment with a pressure of 54.1 kpa and a temperature of 23~25°C. The rats were exposed to hypoxia under these conditions for 14 days, during the experimental time the rats in the model+salidroside group were treated with 50 mg/kg salidroside daily. After the rats were removed from the low-pressure chamber, except for the sham injury group, frozen iron sheets were applied tightly to the back of the rats for 30 s, supplemented with low temperature for frostbite modeling. Blood and skin tissues were collected at 12 hours after modeling for testing. The structural changes in tissue and vascular endothelial cells were observed in the frostbite region. Vascular endothelial cell particulate EMP levels were detected. The levels of ICAM-1, sEPCR, vWF, ET-1 and NO secretion were determined. The expression levels of HIF-1α, p-PI3K, p-Akt and VEGF were detected by Western blot. Results: Salidroside could effectively reduce skin collapse in frostbitten areas. It could reduce the injury of frostbitten tissues, and improve the subcutaneous tissue necrosis and inflammatory cell infiltration. The autophagy of vascular endothelial cells was reduced. Compared with the model group (0.250±0.165)%, the expression of EMPs in the model+salidroside group (2.453±0.196)% was increased significantly (P＜0.01). In addition, the contents of NO (2.622±0.219)pg/ml was also significantly higher than that of the model group (1.616±0.152)pg/ml (P＜0.01), and the content of vWF (233.50±13.43)pg/ml was lower than that of the model group (315.60±8.78)pg/ml (P＜0.05). There was no significant difference in the levels of ICAM-1, sEPCR and ET-1. Salidroside significantly decreased the expressions of p-PI3K, p-Akt, VEGF and HIF-1α protein in vascular endothelial cells of rats with frostbite (P＜0.01). Conclusion: Salidroside can reduce endothelial cell damage, reduce endothelial cell autophagy and promote endothelial cell regeneration. Based on the PI3K/Akt pathway, salidroside has a good protective effect on endothelial cells of rats with frostbite after chronic hypoxia.

Anti-inflammatory and hepatoprotective cembranoid alcohols from the Gum Resin of Boswellia carterii.

Five undescribed cembranoid alcohols, boscartinols A-E (1-5) were discovered from the gum resin of Boswellia carterii. Their structures were elucidated by analyzing the spectroscopic data. Notably, all these five compounds preserved an isopropyl type cembranoid skeleton, featured the same groups of one epoxy ring at C1-C12 and one hydroxy group at C-11, as well as two double bonds migrating from C3 to C9 and one hydroxy group from C3 to C8 within the cembranoid structure. These cembranoids were evaluated for the hepatoprotective and anti-inflammatory activities using two cell models of APAP-induced HepG2 and LPS-induced RAW 264.7. For hepatoprotective activity, compounds 1 and 5 showed remarkable hepatoprotective activity (inhibition rate of 51.6% and 39.8%, respectively) at 10 µM, with the other three compounds of 2-4 showing less potently hepatoprotective. For anti-inflammatory activity, compounds 2-4 showed significant inhibitory effects on NO produced by LPS-induced RAW 264.7 cell (IC50 values of 13.40 µM, 7.08 µM and 14.26 µM), with the other two compounds of 1 and 5 showing less potently anti-inflammatory activities.

A Tobacco Syringe Agroinfiltration-Based Method for a Phytohormone Transporter Activity Assay Using Endogenous Substrates.

Phytohormones are a group of small chemical molecules that play vital roles in plant development, metabolism, and stress responses. Phytohormones often have distinct biosynthesis and signaling perception sites, requiring long- or short-distance transportation. Unlike biosynthesis and signal transduction, phytohormone transport across cells and organs is poorly understood. The transporter activity assay is a bottleneck for the functional characterization of novel phytohormone transporters. In the present study, we report a tobacco syringe agroinfiltration and liquid chromatography tandem mass spectrometry (TSAL)-based method for performing a phytohormone transporter activity assay using endogenous hormones present in tobacco (Nicotiana benthamiana) leaves. A transporter activity assay using this method does not require isotope-labeled substrates and can be conveniently performed for screening multiple substrates by using endogenous hormones in tobacco leaves. The transporter activities of three known hormone transporters, namely AtABCG25 for abscisic acid, AtABCG16 for jasmonic acid, and AtPUP14 for cytokinin, were all successfully validated using this method. Using this method, cytokinins were found to be the preferred substrates of an unknown maize (Zea mays) transporter ZmABCG43. ZmABCG43 transporter activities toward cytokinins were confirmed in a cytokinin long-distance transport mutant atabcg14 through gene complementation. Thus, the TSAL method has the potential to be used for basic substrate characterization of novel phytohormone transporters or for the screening of novel transporters for a specific phytohormone on a large scale.

Clinical characteristics and long-term outcomes of endovascular treatment of renal artery fibromuscular dysplasia with branch lesions.

BACKGROUND: Renal artery fibromuscular dysplasia (FMD) can cause arterial stenosis, dissection, and aneurysm of renal arteries. This study aimed to analyze the clinical characteristics and evaluate the long-term outcomes of renal branch artery FMD in children and adults. METHODS: Sixty-one patients with renal artery FMD underwent endovascular treatment, including 23 children and 38 adults. They were divided into two groups, the main artery FMD group (n = 40, with severe stenosis located in the main renal artery) and the branch artery FMD group (n = 21, with only the branch lesions in unilateral or bilateral branch artery). The clinical characteristics and long-term outcomes of these pediatric and adult patients were evaluated. RESULTS: The incidence of branch FMD was higher in children than in adults (P = 0.005). Thirteen children showed one or more branch artery involvements. Hypertension and headache were the most common symptoms. The branch aneurysm with coexisting stenosis was more common in patients with branch artery FMD. During the follow-up, blood pressure was normal in 8 patients and lowered in 11 patients in the branch FMD group. The patient's glomerular filtration was increased in 61 patients (P < 0.001). Four-year freedom from reintervention in 21 branch artery FMD patients was lower than that in 40 main artery FMD patients (P < 0.05). CONCLUSIONS: A higher incidence of renal branch artery FMD was observed in children than in adults. Endovascular treatment with balloon angioplasty can be used for treating renal branch artery FMD.

Femoral epithelioid hemangioendothelioma detected with magnetic resonance imaging and positron emission tomography/computed tomography: A case report.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is an uncommon low-grade aggressive vascular tumor. It can occur in almost all locations, but is rarely encountered in bone. CASE SUMMARY: We report a 23-year-old man who presented with left hip pain with no obvious cause. X-ray revealed bone destruction in the left femoral neck with sclerosis at the edges of the lesions. Magnetic resonance imaging (MRI) showed bone destruction in the medullary cavity of the left femoral head and neck. 18F-deoxyglucose-positron emission tomography/computed tomography (PET/CT) imaging showed bone destruction in the left ischium, acetabulum, and left femoral head neck, accompanied by increased radioactive uptake; the maximum standard uptake value was 4.2. Histopathologic examination revealed spindle-shaped mesenchymal tissue hyperplasia with scattered epithelioid cells. The patient underwent left femoral head replacement surgery. No signs of recurrence were observed as of the 18-mo follow-up. CONCLUSION: The definitive diagnosis of femoral EHE can be established aided by the MRI and PET/CT findings.

IL­6 plays a crucial role in epithelial­mesenchymal transition and pro­metastasis induced by sorafenib in liver cancer.

Interleukin­6 (IL­6) is involved in various biological responses, including tumor progression, metastasis and chemoresistance. However, the role and molecular mechanism of IL­6 in the treatment of sorafenib in liver cancer remain unclear. In the present study, through western blot analysis, Transwell assay, flow cytometric assay, ELISA analysis and immunohistochemistry it was revealed that sorafenib promoted metastasis and induced epithelial­mesenchymal transition (EMT) in liver cancer cells in vitro and in vivo, and significantly increased IL­6 expression. Endogenous or exogenous IL­6 affected metastasis and EMT progression in liver cancer cells through Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling. Knocked out IL­6 markedly attenuated the pro­metastasis effect of sorafenib and increased the susceptibility of liver cancer cells to it. In conclusion, the present results indicated that IL­6/STAT3 signaling may be a novel therapeutic strategy for liver cancer.

M1 macrophages-derived extracellular vesicles elevate microRNA-185-3p to aggravate the development of atherosclerosis in ApoE-/- mice by inhibiting small mothers against decapentaplegic 7.

OBJECTIVE: Extracellular vesicles (EVs) are vital mediators of transferring microRNAs (miRNAs). We focused on effect of miR-185-3p that mediated by macrophages-derived EVs on atherosclerosis (AS) by targeting small mothers against decapentaplegic 7 (Smad7). METHODS: EVs were extracted from M1 macrophages and identified. ApoE-/- mice were treated with EVs, EVs containing miR-185-3p inhibitor or mimic, then the pathological changes of mouse aorta were observed. The levels of blood lipid, cell adhesion molecules, oxidative stress factors, inflammatory factors, and proliferation and apoptosis of vascular endothelial cells were assessed. Expression of miR-185-3p and Smad7 was detected and the targeting relationship between miR-185-3p and Smad7 was validated. RESULTS: MiR-185-3p was upregulated while Smad7 was downregulated in atherosclerotic mouse aorta. M1 macrophages-derived EVs elevated miR-185-3p to promote development of AS pathology and levels of blood lipid, endothelial cellular adhesion, oxidative stress factors and inflammatory factors, suppressed cell proliferation and promoted cell apoptosis of vascular endothelial cells in atherosclerotic mice through downregulating Smad7. Smad7 was a target gene of miR-185-3p and miR-185-3p could inhibit expression of Smad7. CONCLUSION: M1 macrophages-derived EVs and upregulated miR-185-3p aggravated the development of AS in ApoE-/- mice by negatively regulating Smad7. This research may further the understanding of AS mechanism.

The DLG1-AS1/miR-497/YAP1 axis regulates papillary thyroid cancer progression.

The long non-coding RNA (lncRNA), DLG1-AS1, is upregulated in papillary thyroid cancer (PTC) tissues and cell lines. Here, we found that increased expression of DLG1-AS1 caused lymph node metastasis and advanced tumor-node-metastasis (TNM) stage. DLG1-AS1 knockdown inhibited proliferation, invasion, and migration of PTC cells, and impaired tumorigenesis in vivo in mouse xenografts. DLG1-AS1 functions as a competing endogenous RNA (ceRNA) for miR-497. Further investigation revealed that DLG1-AS1 regulated yes-associated protein 1 (YAP1; a known target of miR-497) by competitively binding to miR-497. Moreover, inhibition of miR-497 abrogated the inhibitory effects of DLG1-AS1 depletion on PTC cells. These findings demonstrate that the DLG1-AS1-miR-497-YAP1 axis promotes the growth and metastasis of PTC by forming a ceRNA network.