Antifungal bio-coating of endotracheal tube built by overexpressing the MCP1 gene of Saccharomyces boulardii and employing hydrogel as a "house" to antagonize Candida albicans.

BACKGROUND: For some ICU patients, an artificial airway must be established with an endotracheal tube, but Candida albicans can easily adhere to the tube surface and form a biofilm, leading to potentially life threatening fungal infections. Therefore, it is urgent to prevent and reduce C. albicans infections introduced by the endotracheal tube. However, there are few antifungal drugs effective against C. albicans, and each of these drugs may have adverse effects on human cells. Saccharomyces boulardii is regarded as an alternative strategy to inhibit the adhesion of C. albicans, but it is affected by environmental stress. We hypothesized that it is feasible to strengthen the antagonistic ability of S. boulardii via encapsulating and genetically modification. METHODS: In this study, a bioactive material carrying the overexpressed MCP1 gene of Saccharomyces boulardii was constructed based on one-step photo-crosslinking. This material achieved spatial growth control of S. boulardii by encapsulating each S. boulardii cell within a hydrogel pore. The bioactive material was coated on an endotracheal tube and tested for its ability to inhibit the adhesion of C. albicans. Additionally, the material's antagonistic activity towards C. albicans was evaluated by detecting intracellular Adenosine-triphosphate content, reactive oxygen species level and the activity of antioxidative enzymes. Tissue invasion experiment was executed to further evaluate the anti-adhesion ability of S. boulardii bio-coating. RESULTS: Encapsulating the overexpression of MCP1 by S. boulardii in hydrogel pores enhanced the viability of probiotics in the presence of high salt and oxidation stress. When used as the coating of an endotracheal tube, the S. boulardii bioactive material efficiently inhibited the adhesion of C. albicans by impairing the activities of superoxide dismutase and catalase and disturbing mitochondrial functions. In vivo, the S. boulardii bioactive material coating displayed good biocompatibility and reduced the host tissue invasion and virulence of C. albicans. CONCLUSIONS: The integration of genetic modification and immobilization model breaks the bottleneck of previous application of microorganisms, and provides a new way to prevent fungal infections introduced by endotracheal tubes.

Retraction Notice to: MicroRNA-494 Inhibits the LRG1 Expression to Induce Proliferation and Migration of VECs in Rats following Myocardial Infarction.

[This retracts the article DOI: 10.1016/j.omtn.2019.08.007.].

MicroRNA-30e-3p reduces coronary microembolism-induced cardiomyocyte pyroptosis and inflammation by sequestering HDAC2 from the SMAD7 promoter.

This study investigates the mechanism by which microRNA (miR)-30e-3p reduces coronary microembolism (CME)-induced cardiomyocyte pyroptosis and inflammation. Cardiac function tests, histological staining, and transmission electron microscopy were performed on CME-model rats injected with adeno-associated viral vectors. Cardiomyocytes were transfected 24 h before a cellular model of pyroptosis was established via treatment with 1 µg/mL lipopolysaccharide (LPS) for 4 h and 5 mM ATP for 30 min. Pyroptosis, inflammation, and Wnt/ß-catenin signaling in cardiomyocytes were detected. Dual-luciferase reporter assays and/or RNA pull-down assays were performed to verify the binding of miR-30e-3p to HDAC2 mRNA or HDAC2 to the SMAD7 promoter. Chromatin immunoprecipitation was used to assess the level of H3K27 acetylation at the SMAD7 promoter. miR-30e-3p and SMAD7 expression levels were downregulated and HDAC2 expression was upregulated with CME. The overexpression of miR-30e-3p restored cardiac functions in CME-model rats and reduced serum cTnI, IL-18, and IL-1ß levels, microinfarcts, inflammatory cell infiltration, apoptosis, collagen content, and GSDMD-N, cleaved caspase-1, and NLRP3 expression in the myocardium, but these effects were reversed by SMAD7 knockdown. The overexpression of miR-30e-3p or knockdown of HDAC2 reduced LDH, IL-18, and IL-1ß secretion, propidium iodide intake, and GSDMD-N, NLRP3, cleaved caspase-1, Wnt3a, Wnt5a, and ß-catenin expression in the cardiomyocyte model. miR-30e-3p inhibited the expression of HDAC2 by binding HDAC2 mRNA. HDAC2 repressed the expression of SMAD7 by catalyzing H3K27 deacetylation at the SMAD7 promoter. miR-30e-3p, by binding HDAC2 to promote SMAD7 expression, reduces CME-induced cardiomyocyte pyroptosis and inflammation.

SparNet: A Convolutional Neural Network for EEG Space-Frequency Feature Learning and Depression Discrimination.

Depression affects many people around the world today and is considered a global problem. Electroencephalogram (EEG) measurement is an appropriate way to understand the underlying mechanisms of major depressive disorder (MDD) to distinguish depression from normal control. With the development of deep learning methods, many researchers have adopted deep learning models to improve the classification accuracy of depression recognition. However, there are few studies on designing convolution filters for spatial and frequency domain feature learning in different brain regions. In this study, SparNet, a convolutional neural network composed of five parallel convolutional filters and the SENet, is proposed to learn EEG space-frequency domain characteristics and distinguish between depressive and normal control. The model is trained and tested by the cross-validation method of subject division. The results show that SparNet achieves a sensitivity of 95.07%, a specificity of 93.66%, and an accuracy of 94.37% in classification. Therefore, our results can conclude that the proposed SparNet model is effective in detecting depression using EEG signals. It also indicates that the combination of spatial information and frequency domain information is an effective way to identify patients with depression.

Possible implication of miR-142-3p in coronary microembolization induced myocardial injury via ATXN1L/HDAC3/NOL3 axis.

This study aims to explore the mechanism underlying miR-142-3p regulating myocardial injury induced by coronary microembolization (CME) through ATXN1L. miR-142-3p overexpression or ATXN1L knockout adenovirus vectors were injected into rats before CME treatment. Cardiac functions were examined by echocardiography, and pathologies of myocardial tissues were assessed. Then, serum cTnI and IL-1ß contents and concentrations of IL-1ß and IL-18 in cell supernatant were measured. Immunofluorescence determined the localization of histone deacetylase 3 (HDAC3). The interaction between miR-142-3p and ATXN1L as well as the binding between HDAC3 and histone 3 (H3) was identified. The binding of ATXN1L and HDAC3 to NOL3 promoter was verified using ChIP. The levels of ATXN1L, NOL3, and miR-142-3p as well as apoptosis- and pyroptosis-related proteins and acetyl-histone 3 (ac-H3) were evaluated. CME treatment impaired the cardiac functions in rats and increased cTnI content. CME rats showed microinfarction foci in myocardial tissues. After CME treatment, miR-142-3p and NOL3 were modestly expressed while ATXN1L content was elevated, in addition to increases in apoptosis and pyroptosis. miR-142-3p overexpression or ATXN1L knockout alleviated CME-induced myocardial injury, cardiomyocyte apoptosis, and pyroptosis in myocardial tissues. miR-142-3p regulated ATXN1L expression in a targeted manner. In the cellular context, miR-142-3p overexpression attenuated apoptosis and pyroptosis in cardiomyocytes, which was partly counteracted by ATXN1L overexpression. ATXN1L functioned on cardiomyocytes by promoting deacetylation of H3 through HDAC3 and thus inhibited NOL3 expression. Inhibition of HDAC3 or overexpression of NOL3 ameliorated the promotive effects of ATXN1L on cardiomyocyte apoptosis and pyroptosis. In vivo and in vitro evidence in this study supported that miR-142-3p could attenuate CME-induced myocardial injury via ATXN1L/HDAC3/NOL3. HIGHLIGHTS: CME model witnessed aberrant expression of miR-142-3p, ATXN1L, and NOL3; miR-142-3p negatively regulated ATXN1L; miR-142-3p mediated CME-induced myocardial injury through ATXN1L; ATXN1L promoted deacetylation of H3 through HDAC3 and thus inhibited NOL3 expression; ATXN1L acted on cardiomyocyte apoptosis and pyroptosis through HDAC3/NOL3 axis.

miR-451-3p alleviates myocardial ischemia/reperfusion injury by inhibiting MAP1LC3B-mediated autophagy.

OBJECTIVE AND DESIGN: We aim to explore the molecular mechanism of myocardial ischemia-reperfusion injury (MIRI). METHODS: The H9C2 cells were cultured under hypoxia/reoxygenation (H/R) condition to induce myocardial injury in vitro. The expression of miR-451-3p and MAP1LC3B was detected by RT-qPCR. Dual-luciferase reporter assay and RNA pull-down assay were performed to examine the relationship between microRNA (miR)-451-3p and MAP1LC3B. CCK8 was used to test cell viability. The level of LDH and CK was evaluated via ELISA. Immunofluorescence assay and flow cytometry were applied to detect autophagy and apoptosis, respectively. Autophagy-related protein expressions were determined by western blotting. Furthermore, an in vivo rat model of MIRI was established by subjection to 30 min ischemia and subsequently 24 h reperfusion for validation of the role of miR-451-3p in regulating MIRI in vivo. RESULTS: miR-451-3p was down-regulated in MIRI, and miR-451-3p mimics transfection alleviated autophagy and apoptosis induced by MIRI. miR-451-3p could target MAP1LC3B directly. Co-transfection miR-451-3p mimics and pcDNA 3.1 MAP1LC3B curbed the protected effects of miR-451-3p mimics on MIRI. CONCLUSIONS: miR-451-3p played a protective role in MIRI via inhibiting MAP1LC3B-mediated autophagy, which may provide new molecular targets for the treatment of MIRI and further improves the clinical outcomes of heart diseases.

Efficacy and Safety of a Combination of Shenmai Injection plus Chemotherapy for the Treatment of Lung Cancer: A Meta-Analysis.

OBJECTIVE: To perform a systematic evaluation of the efficacy and safety of combined treatment of Shenmai injection and chemotherapy for lung cancer. METHODS: A literature search for randomized controlled trials (RCTs) describing the treatment of lung cancer by Shenmai injection and chemotherapy or chemotherapy alone was performed using the PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Value In Paper (VIP), China BioMed, and Wanfang databases. The databases were searched for entries published before September 1, 2019. RESULTS: Thirty-seven RCTs, comprising a total of 2808 cases, were included in the present meta-analysis. Of these, 1428 cases were treated by Shenmai injection plus chemotherapy, and 1380 cases were treated only by chemotherapy. The results of meta-analysis showed that the combined treatment (Shenmai injection plus chemotherapy) increased the short-term efficacy of treatment (relative risk [RR] = 1.183, 95% confidence interval [CI] = 1.043-1.343, P < 0.01) and improved patients' quality of life (RR = 1.514, 95%CI = 1.211-1.891, P < 0.01) compared with chemotherapy alone. With regard to the adverse effects, the combined treatment markedly reduced the incidence of white blood cell (WBC) reduction (RR = 0.846, 95%CI = 0.760-0.941, P < 0.01), platelet reduction (RR = 0.462, 95% CI = 0.330-0.649, P < 0.01), and hemoglobin reduction (RR = 0.462, 95% CI = 0.330-0.649, P < 0.01) and alleviated drug-induced liver injury (RR = 0.677, 95%CI = 0.463-0.990, P < 0.05). However, it did not offer a significant protective effect (RR = 0.725, 95%CI = 0.358-1.468, P < 0.05). The effect of the combined treatment on the occurrence of vomiting was considerable (RR = 0.889, 95%CI = 0.794-0.996, P < 0.05), and the combined treatment markedly increased the immunity of patients with lung cancer. CONCLUSION: The combined treatment of Shenmai injection plus chemotherapy enhanced the short-term efficacy of chemotherapy, improved the patient quality of life, alleviated the adverse effects of chemotherapeutics, and increased the patient immunity. These results should be confirmed by large-scale, high-quality RCTs.

6-Gingerol relieves myocardial ischaemia/reperfusion injury by regulating lncRNA H19/miR-143/ATG7 signaling axis-mediated autophagy.

Myocardial ischemia/reperfusion injury (MIRI) causes severe damage in cardiac tissue, thereby resulting in a high rate of mortality. 6-Gingerol (6-G) is reported to play an essential role in alleviating MIRI. However, the underlying mechanism remains obscure. This study was intended to explore the potential mechanism by which 6-G functions. Q-PCR was employed to quantify the relative RNA levels of long noncoding RNA (lncRNA) H19 (H19), miR-143, and ATG7, an enzyme essential for autophagy, in HL-1 cells. Western blotting, immunofluorescence, and immunohistochemistry were employed for protein evaluation in cultured cells or mouse tissues. Cell viability, cytotoxicity, and apoptosis were analysed by CCK-8, LDH, and flow cytometry assays, respectively. The binding sites for miR-143 were predicted using starBase software and experimentally validated through a dual-luciferase reporter system. Here, we found that 6-G elevated cellular H19 expression in hypoxia/reoxygenation (H/R)-treated HL-1 cells. Moreover, 6-G increased Bcl-2 expression but reduced cleaved caspase 3 and caspase 9 protein levels. Mechanistically, H19 directly interacted with miR-143 and lowered its cellular abundance by acting as a molecular sponge. Importantly, ATG7 was validated as a regulated gene of miR-143, and the depletion of miR-143 by H19 caused an increased in ATG7 expression, which in turn promoted the autophagy process. Last, mouse experiments highly supported our in vitro findings that 6-G relieves MIRI by enhancing autophagy. The H19/miR-143/ATG7 axis was shown to be critical for the function of 6-G in relieving MIRI.

Exosomal LINC00174 derived from vascular endothelial cells attenuates myocardial I/R injury via p53-mediated autophagy and apoptosis.

In this study, we aim to investigate the regulation of specific long non-coding RNAs (lncRNAs) on the progression of ischemia/reperfusion (I/R) injury. We identified and characterized the exosomes derived from mouse primary aortic endothelial cells. Subsequently, we found that these exosomes expressed typical exosomal markers and high levels of LINC00174, which significantly ameliorated I/R-induced myocardial damage and suppressed the apoptosis, vacuolation, and autophagy of myocardial cells. Mechanistic approaches revealed that LINC00174 directly interacted with SRSF1 to suppress the expression of p53, thus restraining the transcription of myocardin and repressing the activation of the Akt/AMPK pathway that was crucial for autophagy initiation in I/R-induced myocardial damage. Moreover, this molecular mechanism was verified by in vivo study. In summary, exosomal LINC00174 generated from vascular endothelial cells repressed p53-mediated autophagy and apoptosis to mitigate I/R-induced myocardial damage, suggesting that targeting LINC00174 may be a novel strategy to treat I/R-induced myocardial infarction.

Overexpression of MiR-29b-3p Inhibits Atrial Remodeling in Rats by Targeting PDGF-B Signaling Pathway.

PURPOSE: Studies have found that microRNAs (miRNAs) are closely associated with atrial fibrillation, but their specific mechanism remains unclear. The purpose of this experiment is to explore the function of miR-29b-3p in regulating atrial remodeling by targeting PDGF-B signaling pathway and thereby also explore the potential mechanisms. METHODS: We randomly divided twenty-four rats into four groups. Caudal intravenous injections of angiotensin-II (Ang-II) were administered to establish atrial fibrosis models. Expressions of miR-29b-3p and PDGF-B were then tested via RT-PCR, western blot, and immunohistochemistry. Binding sites were then analyzed via the bioinformatics online software TargetScan and verified by Luciferase Reporter. We used Masson staining to detect the degree of atrial fibrosis, while immunofluorescence and western blot were used to detect the expressions of Collagen-I and a-SMA. We used immunohistochemistry and western blot to detect the expression of connexin 43 (Cx43). RESULTS: In comparison with the Ang-II group, miR-29b-3p was seen to lower the degree of atrial fibrosis, decrease the expression of fibrosis markers such as Collagen-I and a-SMA, and increase the protein expression of Cx43. MiR-29b-3p can lower the expression of PDGF-B, while the Luciferase Reporter showed that PDGF-B is the verified target gene of miR-29b-3p. CONCLUSIONS: MiR-29b-3p was able to reduce atrial structural and electrical remodeling in the study's rat fibrosis model. This biological function may be expressed through the targeted regulation of the PDGF-B signaling pathway.

miR-346 Inhibited Apoptosis Against Myocardial Ischemia-Reperfusion Injury via Targeting Bax in Rats.

PURPOSE: Myocardial ischemia-reperfusion injury (MIRI) is a common pathophysiological process after occlusion of the blood vessels to restore blood supply. Apoptosis is one of the ways of myocardial cell death in this process. MicroRNAs (miRNAs), a class of short and noncoding RNAs, are involved in multiple biological processes by post-transcriptionally targeting their downstream effectors. To date, whether miRNAs exert biological effects in myocardial ischemia-reperfusion (I/R) injury remains to be further studied. METHODS: In this study, we induced MIRI model by ligating rat left anterior descending artery (LAD) for 30 mins and reperfusion for 2 hrs. The differential expression profile of miRNAs in rat models of MIRI was analyzed by miRNAs sequencing. RESULTS: We found that miRNAs sequencing analysis showed the expressions of 15 types of miRNAs, including miR-346, were downregulated and 29 types of miRNAs were elevated in the MIRI rat model. We observed the key regulator of apoptosis Bax was a predicted downstream target of miR-346 using online software TargetScan. And luciferase reporter assay was utilized to certify this prediction. Over-expression of miR-346 can attenuate myocardial injury and narrow infarct area by inhibiting myocardial cell apoptosis in rat models. CONCLUSION: This study revealed a novel pathway, miR-346/Bax axis, in the regulation of apoptosis in MIRI and which might be a new molecular mechanism and therapeutic target.

Downregulation of long noncoding RNA SNHG14 suppresses cell proliferation and invasion by regulating EZH2 in pancreatic ductal adenocarcinoma (PDAC).

BACKGROUNDS: Previous studies have showed that long non-coding RNAs (lncRNAs) are critical regulators in many cancers. The aim of this study is to investigate the clinical role and functional effects of long non-coding RNA SNHG14 in pancreatic ductal adenocarcinoma (PDAC). METHODS: The expression of SNHG14 in 58 pairs of pancreatic cancer tissues and adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR) analysis. The correlations between SNHG14 expression and PDAC patients' clinicopathological characteristics and prognosis were statistically assessed. Cell counting kit-8 (CCK8) and transwell cell invasion assays were employed to detect the capacities of cell proliferation and cell invasion. The western blot analysis was used to detected the expression of E-cadherin and Vimentin. RESULTS: In the study, we found that SNHG14 expression was higher in PDAC tissue compared to adjacent normal tissues by qRT-PCR analysis. Higher SNHG14 expression was significantly associated with advanced TNM stage and positive lymph node metastasis in PDAC patients. Furthermore, we demonstrated that higher SNHG14 expression acted as a poor predictor in PDAC patients compared with lower SNHG14 expression. Moreover, we showed that higher SNHG14 expression promoted cell proliferation, cell colony formation and cell invasion ability in PDAC. Upregulation of SNHG14 expression promoted cell invasion by affecting E-cadherin expression via interacting with EZH2. CONCLUSIONS: Thus, these results indicated that SNHG14 expression acts as a prognostic maker for PDAC and potential target of PDAC treatment.

Revealing new landscape of cardiovascular disease through circular RNA-miRNA-mRNA axis.

Non-coding RNA (ncRNA) is a kind of RNA, produced by genomic transcription and does not encode protein, but can regulate the function of genes, thus widely regulating pathological and physiological processes. The dynamic balance of the reticular structure between them is needed to regulate the homeostasis, the abnormal regulation of one of them may lead to the occurrence of the disease. CircRNA is mainly involved in the evolution of CVD through sponge-like regulation of miRNAs, subsequently regulating miRNAs and their targets, mRNA functions. The role of circRNA-miRNA-mRNA axis in pathogenesis of cardiovascular diseases has been recently reported and highlighted. In this review, the emerging roles of circRNA-miRNA-mRNA axis in cardiovascular pathophysiology and regulation were discussed, with a novel focus on cardioprotective network activities of the circRNA.

LncRNA TUG1 mediates ischemic myocardial injury by targeting miR-132-3p/HDAC3 axis.

Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long noncoding RNA taurine upregulated gene 1 (TUG1). In this study, we explored the functional significance and molecular mechanisms of TUG1/miR-132-3p axis in ischemia-challenged cardiomyocytes. In primary cardiomyocytes challenged with H2O2, expressions of miR-132-3p, TUG1, and other target proteins were measured by RT quantitative PCR or Western blot analysis; cell viability by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay; apoptosis by annexin V and propidium iodide staining; the abundance of acetylated H3K9 or histone deacetylase 3 (HDAC3) within the promoter of target genes by chromatin immunoprecipitation; the direct interaction between miR-132-3p and HDAC3 or TUG1 by luciferase reporter assay. The biological significance of miR-132-3p, TUG1, and HDAC3 was assessed using miR-132-3p mimic, siRNA-targeting TUG1 and HDAC3 inhibitor RGF966, respectively, in H2O2-challenged cells in vitro or ischemia-reperfusion (I/R)-induced AMI in vivo. miR-132-3p was downregulated, whereas TUG1 upregulated in H2O2-challenged cardiomyocytes. Overexpressing miR-132-3p or knocking down TUG1 significantly improved viability, inhibited apoptosis, and reduced ROS production in H2O2-stressed cardiomyocytes in vitro and alleviated I/R-induced AMI in vivo. Mechanistically, TUG1 sponged miR-132-3p and upregulated HDAC3, which reduced the acetylation of H3K9 and epigenetically inhibited expressions of antioxidative genes, including Bcl-xL, Prdx2, and Hsp70. The TUG1/miR-132-3p/HDAC3 axis critically regulates ROS production and the pathogenic development of AMI. Targeting TUG1, upregulating miR-132-3p, or inhibiting HDAC3 may benefit AMI treatment.NEW & NOTEWORTHY Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long noncoding RNA taurine upregulated gene 1 (TUG1). However, the underlying mechanisms remain elusive. In the present study, we reported for the first time that H2O2 or ischemia-reperfusion-induced TUG1, by sponging microRNA 132-3p, activated histone deacetylase 3, which in turn targeted multiple protective genes, stimulated intracellular ROS accumulation, and aggravated the injury of AMI. Our findings might provide some insight to seek new targets for AMI treatment.

Micro-reentry right atrial tachycardia originating from fossa ovalis: a case report of high-density mapping by PentaRay catheter.

BACKGROUND: Micro-reentry tachycardia usually emerges in scar tissues related to post-atrial fibrillation ablation and cardiomyopathy. It is difficult to identify the micro-reentry circuit accurately by conventional mapping method. CASE SUMMARY: A 74-year-old man presented with paroxysmal atrial tachycardia (AT) presenting as palpitations. He was evaluated by an electrophysiological examination using a high-density CARTO mapping system. The mapping results showed the AT with a cycle length of 184 ms was focused on his right atrial fossa ovalis (FO). In this small area, the high-density mapping demonstrated a significant micro-reentrant tachycardia. Radiofrequency ablation at the centre of the micro-reentrant circuit successfully terminated the AT. No recurrences were observed during a 12-month follow-up. DISCUSSION: This case demonstrated a micro-reentrant AT originates from the FO without cardiomyopathy or previous ablation with specific loops. This is an unusual location for AT though and can cause difficulty for operators if it terminates or is non-sustained. High-density mapping using a PentaRay catheter can effectively characterize micro-reentrant circuits and determine the real target for ablation therapy.

miRNA-708 functions as a tumor suppressor in colorectal cancer by targeting ZEB1 through Akt/mTOR signaling pathway.

BACKGROUND: Colon cancer, or colorectal cancer (CRC), is a type of cancer that develops from large bowel. Previous data has demonstrated that microRNAs (miRNAs) may be involved in the formation and progression of CRC. The deregulation of miR-708 has been identified in multiple types of cancer. However, to the best of our knowledge, there are no data concerning the expression and role of miR-708 in CRC. METHODS: In this study, RT-PCR and Flow Cytometry were used to examine the expression and role of miR-708 and ZEB1 in proliferation and apoptosis. Transwell was used to examine the role of miR-708 and ZEB1 in invasion and migration. Western blot and qRT-PCR were conducted to determine the alteration of protein and miR-708 levels, respectively. RESULTS: MiR-708 was significantly downregulated in CRC tissues and cell lines. The restoration of the expression of miR-708 suppressed cell proliferation, induced apoptosis, and reduced metastasis in CRC in vitro. Additionally, bioinformatics analysis predicted ZEB1 as a novel target gene of miR-708. Furthermore, ZEB1 was upregulated in CRC, which was negatively correlated with miR-708 expression. Further studies showed that the overexpression of miR-708 and silence of ZEB1 inhibited stage of CRC via inhibiting AKT/mTOR signaling pathway in CRC cells. CONCLUSION: Taken together, these results indicate that miR-708 plays an important role in suppressing the development of CRC by directly targeting ZEB1 through AKT/mTOR signaling pathway, suggesting that miR-708 is a novel, effective therapeutic target for treating patients with CRC.

Role of surface functionalities of nanoplastics on their transport in seawater-saturated sea sand.

The transport and retention of nanoplastics (NP, 200 nm nanopolystyrene) functionalized with surface carboxyl (NPC), sulfonic (NPS), low-density amino (negatively charged, NPA-), and high-density amino (positively charged, NPA+) groups in seawater-saturated sand with/without humic acid were examined to explore the role of NP surface functionalities. The mass percentages of NP recovered from the effluent (Meff) with a salinity of 35 practical salinity units (PSU) were ranked as follows: NPC (19.69%) > NPS (16.37%) > NPA+ (13.33%) > NPA- (9.78%). The homoaggregation of NPS and NPA- was observed in seawater. The transport of NPA- exhibited a ripening phenomenon (i.e., a decrease in the transport rate with time) due to the high attraction of NP with previously deposited NP, whereas monodispersed NPA+ presented a low Meff value because of the electrostatic attraction between NPA+ and negatively charged sand. Retention experiments showed that the majority of NPC, NPS and NPA+ accumulated in a monolayer on the sand surface, whereas NPA- accumulated in multiple layers. Suwannee River humic acid (SRHA) could remarkably improve the transportability of NPC, NPS, and NPA- by increasing steric repulsion. The strong attraction between NPA+ and the deposited NPA+ in the presence of SRHA triggered the weak ripening phenomenon. As seawater salinity decreased from 35 PSU to 3.5 PSU, the increase in electrostatic repulsion of NP-NP and NP-sand enhanced the transport of NPC, NPS, and NPA-, and the ripening of NPA- breakthrough curves disappeared. In deionized water, NPC, NPS, and NPA- achieved complete column breakthrough because the electrostatic repulsion between NP and sand intensified. However, the Meff values of NPA+ in 3.5 PSU seawater and deionized water presented limited increments of 15.49% and 23.67%, respectively. These results indicated that the fate of NP in sandy marine environments were strongly affected by NP surface functionalities, seawater salinity, and coexisting SRHA.

MicroRNA-494 Inhibits the LRG1 Expression to Induce Proliferation and Migration of VECs in Rats following Myocardial Infarction.

Myocardial infarction (MI) is a life-threatening cardiac event that results in extreme damage to the heart muscle. The Wnt signaling pathway has been implicated in the development of heart diseases. Hence, the current study aimed to investigate the role of microRNA (miRNA) in association with the Wnt signaling pathway to identify potential candidates for MI therapy. Differentially expressed miRNAs associated with MI occurrence were screened, and miR-494 was selected for subsequent experiments. Sprague-Dawley rats were included to establish a MI model via intraperitoneal injection of 0.1 mg/kg atropine sulfate and 40 mg/kg pentobarbital sodium. Then, the interaction between miR-494 and LRG1 was identified. The effect of miR-494 on expression of the Wnt signaling pathway-related genes, proliferation, migration, and invasion ability of fibroblasts and vascular endothelial cells (VECs) was subsequently evaluated through a series of gain- and loss-of-function experiments. The results revealed that miR-494 was poorly expressed and LRG1 was highly expressed in MI rats. miR-494 targets and downregulates LRG1, which resulted in the inactivation of the Wnt signaling pathway and promoted proliferation, migration, and invasion ability of fibroblasts and VECs. In conclusion, this study provided evidence suggesting that overexpressed miR-494 could potentially promote the proliferation, migration, and invasion of fibroblasts and VECs in MI through the inactivation of the Wnt signaling pathway by binding to LRG1.