Nickel-Catalyzed α-selective Hydroalkylation of Vinylarenes.

C(sp3) centers adjacent to (hetero)aryl groups are widely present in physiologically active molecules. Metal-hydride-catalyzed hydroalkylation of alkenes represents an efficient means of forging C(sp3)-C(sp3) bonds, boasting advantages as a wide source of substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the hydroalkylation of vinylarenes encounters constraints in terms of substrate scope, necessitating the employment of activated alkyl halides or alkenes containing chelating groups, remains a challenge. In this context, we report a general nickel-hydride-catalyzed hydroalkylation protocol for vinylarenes. Remarkably, this system enables α-selective hydroalkylation of both aryl and heteroaryl alkenes under an extra ligand-free condition, demonstrating excellent coupling efficiency and selectivity. Furthermore, through the incorporation of chiral bisoxazoline ligands, we have achieved regio- and enantioselective hydroalkylation of vinylpyrroles, thereby facilitating the synthesis of α-branched alkylated pyrrole derivatives.

Effects of community ecological network construction on physicochemical, microbial, and quality characteristics of inoculated northeast sauerkraut: A new insight in food fermentation processes.

The enhancement of the quality of northeast sauerkraut can be achieved by inoculation with lactic acid bacteria. However, a comprehensive ecological understanding of the intricate dynamic processes involved is currently lacking, which could yield valuable insights for regulating sauerkraut fermentation. This study compares spontaneously sauerkrauts with the sauerkrauts inoculated with autochthonous Lactiplantibacillus plantarum SC-MDJ and commercial L. plantarum, respectively. We examine their physicochemical properties, quality characteristics, bacterial community dynamics, and ecological network interactions. Inoculation with L. plantarum leads to reduced bacterial community richness and niche breadth, but an increase in robustness, interactions, and assembly processes. Notably, there appears to be a potential correlation between bacterial community structure and quality characteristics. Particularly, sauerkraut inoculated with L. plantarum SC-MDJ may produce a sourness more quickly, possibly attributed to the enhanced ecological role of L. plantarum SC-MDJ. This study establishes a foundation for the targeted regulation of sauerkraut fermentation.

Effect of Inoculation with Autochthonous Lactic Acid Bacteria on Flavor, Texture, and Color Formation of Dry Sausages with NaCl Partly Substituted by KCl.

The effects of inoculating lactic acid bacteria (LAB), specifically Lactiplantibacillus plantarum, Latilactobacillus sakei, Latilactobacillus curvatus, and Weissella hellenica on the flavor, texture, and color formation of dry sausages in which NaCl was partially substituted by 40% KCl, were explored in this study. It was found that LAB inoculation increased the presence of ketones, alcohols, acids, esters, and terpenes. It also reduced the pH, moisture, protein, and fat content, improving the b*-value, flavor, and texture of the sausages. Notably, L. sakei inoculation showed the most significant improvement in dry sausages with NaCl substitutes, especially on the reduction of bitterness. Meanwhile, there was a close positive correlation between the LAB count with the alcohols and esters formation of dry sausage with NaCl substitution (p < 0.05). These findings offer insight into improving the product characteristics of dry sausages using NaCl substitutes.

Improving the bacterial community, flavor, and safety properties of northeastern sauerkraut by inoculating autochthonous Levilactobacillus brevis.

The effect of Levilactobacillus brevis as a starter in northeastern sauerkraut fermentation is still unknown, and further evaluation is worthwhile. Hence, this study aimed to evaluate the effect of autochthonous L. brevis inoculation on the bacterial community succession and formation of flavor and harmful substances in sauerkrauts. Inoculation with L. brevis lowered the pH and increased the total acid content of sauerkrauts (P < 0.05). The nitrite content of the inoculated sauerkraut was significantly lower than that of control (P < 0.05). Moreover, the spoilage bacteria of the inoculated sauerkraut were decreased and nitrogen metabolism was improved. The contents of aldehydes, alcohols, esters, acids, and alkanes increased significantly (P < 0.05), and the sensory attributes such as aroma, sourness, and gloss were also improved. L. brevis was positively and negatively correlated with flavor metabolites and nitrite, respectively, which proved to be a potential starter culture to manufacture sauerkraut.

Exploring potential correlations between bacterial communities, organic acids, and volatile metabolites of traditional fermented sauerkraut collected from different regions of Heilongjiang Province in Northeast China.

In this study, the bacterial communities and flavor metabolites of 27 traditional naturally fermented sauerkraut samples collected from nine regions of Heilongjiang Province in Northeast China were investigated. The dominant genera were Lactobacillus, Pseudomonas, Alcaligenes, Arcobacter, Pseudarcobacter, Lactococcus, Comamonas, Pediococcus, Prevotella, and Insolitispirillum. A total of 148 volatile compounds were detected in seven categories; esters and acids were the most abundant volatiles. Additionally, the highest content (15.96 mg/g) of lactic acid was detected in YC1. Acetic acid, oleic acid, palmitic acid, elaidic acid, and dehydroacetic acid were the key differential volatile compounds, which may be related to the bacterial communities. Spearman's correlation analysis revealed that Lactococcus and Lactobacillus were significantly positively correlated with flavor metabolites, suggesting that they may play a more significant role in flavor formation. The results of this study can help in the development of better quality of fermented vegetables.

Nickel-Catalyzed Remote Asymmetric Hydroalkylation of Alkenyl Ethers to Access Ethers of Chiral Dialkyl Carbinols.

Site- and enantio-selective alkyl-alkyl bond formation is privileged in the retrosynthetic analysis due to the universality of sp3-hybridized carbon atoms in organic molecules. Herein, we report a nickel-catalyzed remote asymmetric hydroalkylation of alkenyl ethers via synchronous implementation of alkene isomerization and enantioselective C(sp3)-C(sp3) bond formation. Regression analysis of catalyst structure-activity relationships accelerates the rational ligand modification through modular regulation. This reaction has several advantages for synthesizing chiral dialkyl carbinols and their ether derivatives, including the broad substrate scope, good functional group tolerance, excellent regioselectivity (>20:1 regioisomeric ratio), and high enantioselectivity (up to 95% enantiomeric excess).

Cobalt-Catalyzed Facial-Selective Hydroalkylation of Cyclopropenes.

Cyclopropene hydrofunctionalization has been a promising strategy for accessing multi-substituted cyclopropanes; however, cyclopropene hydroalkylation remains underdeveloped. Herein, we report a low-valent CoH-catalyzed facial-selective cyclopropene hydroalkylation to access multi-substituted cyclopropanes. This reaction exhibits a broad substrate scope of alkyl halides and cyclopropenes and tolerates many functional groups. Moderate-to-good facial-selectivity is obtained without any directing groups. Mechanism studies provide evidence that alkyl radicals are generated from alkyl halides and irreversible CoH insertion is responsible for the facial-selectivity. Our preliminary exploration demonstrates that asymmetric cyclopropene hydroalkylation can be realized without conspicuous auxiliary groups.

Prognostic impact of white blood cell counts on clinical outcomes in patients with chronic renal insufficiency undergoing percutaneous coronary intervention.

Objective: To determine whether the inclusion of white blood cell (WBC) counts in the SYNTAX score (SS) or SS II models could improve the models' performance for risk stratification in individuals with chronic renal insufficiency (CRI) following percutaneous coronary intervention (PCI). Methods: In total, 2,313 patients with CRI, who were subjected to PCI and had data available on in-hospital WBC (ih-WBC) counts, were recruited. Patients were divided into 3 groups as per their ih-WBC counts (low, medium, and high). The primary endpoints were all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints incorporated myocardial infarction, stroke, unplanned revascularization, and major adverse cardiovascular and cerebrovascular events (MACCEs). Results: During a median follow-up of 3 years, the high WBC group had the highest incidences of CM (2.4% vs. 2.1% vs. 6.7%; p < 0.001), ACM (6.3% vs. 4.1% vs. 8.2%; p < 0.001), unplanned revascularization (8.4% vs. 12.4% vs. 14.1%; p < 0.001), and MACCEs (19.3% vs. 23.0% vs. 29.2%; p < 0.001) among the three groups. Multivariable Cox regression analysis depicted that the risk of ACM and CM in the high WBC group was 2.577 (95% confidence interval [CI]: 1.504-4.415, p < 0.001) and 3.850 (95% CI: 1.835-8.080, p < 0.001) times that in the low WBC group after adjusting for other confounding factors. A combination of ih-WBC counts with SS or SS II significantly improved the risk assessment and prediction of ACM and CM. Conclusion: The ih-WBC counts was associated with the risk of occurrence of ACM, CM, unplanned revascularization, and MACCEs in individuals with CRI following PCI. It provides an incremental predictive value for the occurrence of ACM and CM when included in SS or SS II models.

The guiding value of hybrid resting full-cycle ratio and fractional flow reserve strategy for percutaneous coronary intervention in a Chinese real-world cohort with non-ST elevation acute coronary syndrome.

Objective: The study aimed to assess the correlation and agreement between resting full-cycle ratio (RFR) and fractional flow reserve (FFR), and evaluate the guiding value of a hybrid RFR-FFR strategy for percutaneous coronary intervention (PCI) in a Chinese real-world cohort with non-ST elevation acute coronary syndrome (NSTE-ACS). Materials and methods: A total of 109 patients with NSTE-ACS (149 diseased vessels), who underwent an invasive physiological assessment in Cangzhou Central Hospital, Hebei Medical University, were prospectively enrolled from September 2021 to May 2022. FFR ≤ 0.80 was used as the gold standard for coronary artery functional ischemia. We utilized the Pearson correlation and Bland-Altman analysis to assess the correlation and agreement between RFR and FFR. The diagnostic value of RFR predicting FFR ≤ 0.80 was evaluated in accordance with the receiver operating characteristic (ROC) curve. The hybrid RFR-FFR strategy, which was established according to determining the "gray zone" of RFR (FFR was further assessed using vasodilators only for diseased vessels in the "gray zone"), needed to afford over 95% global agreement with the FFR-only strategy. Results: Resting full-cycle ratio was significantly linearly linked with FFR (R 2 = 0.636, P < 0.001). The accuracy, specificity, and sensitivity for RFR ≤ 0.89 predicting FFR ≤ 0.80 were 81.2, 70.8, and 86.1%, respectively. The area under the ROC curve for RFR predicting FFR ≤ 0.80 was 0.881 (P < 0.001), and the cutoff value was 0.90. The "gray zone" of RFR was 0.85-0.93. The positive and negative predictive values of the hybrid RFR-FFR strategy were 0.95 and 0.93, respectively. The hybrid RFR-FFR strategy exhibited an agreement of 96.0% with FFR and obviated the need for a vasodilator by 60.4%. Conclusion: Resting full-cycle ratio and FFR have high correlation and consistency. The hybrid RFR-FFR strategy highlights considerably enhanced agreement with the FFR-only strategy, whilst making the requirement of vasodilator administration less than a half.

Nickel-Catalyzed Switchable Site-Selective Alkene Hydroalkylation by Temperature Regulation.

Regiodivergent alkene functionalization that produces either regioisomer starting from the same raw materials is desirable. Herein, we report a nickel-catalyzed switchable site-selective alkene hydroalkylation. The selection of reaction temperatures leads to protocols that provide regiodivergent hydroalkylated products starting from a single alkene substrate. This protocol allows the convenient synthesis of α- and ß-branched protected amines, both of which are important to the fields of pharmaceutical chemistry and biochemistry. In addition, enantioenriched ß-branched alkylamines can be accessed in a catalytic asymmetric variant. Preliminary mechanistic studies indicate that the formation of a more stable nickelacycle provides the driving force of migration. The thermodynamic and kinetic properties of different reduction elimination intermediates are responsible for the switchable site-selectivity.

[Establishment of a nomogram prediction model for coronary artery disease risk in elderly patients with acute myocardial infarction].

OBJECTIVE: To establish a nomogram model for predicting the risk of coronary artery disease in elderly patients with acute myocardial infarction (AMI). METHODS: The clinical data of elderly patients with AMI who underwent coronary angiography in the department of cardiology of Cangzhou Central Hospital from July 2015 to March 2020 were analyzed, including age, gender, smoking history, underlying diseases, family history, blood pressure, left ventricular ejection fraction (LVEF), and several biochemical indicators at admission, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein [Lp(a)], apolipoproteins (ApoA, ApoB), ApoA/B ratio, total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil), fasting blood glucose (FBG) and uric acid (UA). Patients were divided into model group (2 484 cases) and validation group (683 cases) according to the ratio of 8:2. According to Gensini score, the model group and validation group were divided into mild lesion group (0-20 points) and severe lesion group (≥ 81 points). The differences of each index between different coronary lesion degree groups were compared. Lasso regression and Logistic regression were used to analyze the risk factors of aggravating coronary lesion risk in elderly patients with AMI, and then the nomogram prediction model was established for evaluation and external validation. RESULTS: (1) In the model group, there were significant differences in the family history of coronary heart disease, FBG and HDL-C between the mild lesion group (411 cases) and the severe lesion group (417 cases) [family history of coronary heart disease: 3.6% vs. 7.7%, FBG (mmol/L): 5.88±1.74 vs. 6.43±2.06, HDL-C (mmol/L): 1.48±0.69 vs. 1.28±0.28, all P < 0.05]. In the validation group, there were significant differences between the mild lesion group (153 cases) and the severe lesion group [132 cases; FBG (mmol/L): 5.58±0.88 vs. 6.85±0.79, HDL-C (mmol/L): 1.59±0.32 vs. 1.16±0.21, both P < 0.05]. (2) Lasso regression analysis showed that family history of coronary heart disease, FBG, and HDL-C were risk factors of coronary artery disease in elderly patients with AMI, with coefficients 0.118, 0.767, and -0.558, respectively. Logistic regression analysis showed that FBG [odds ratio (OR) = 1.479, 95% confidence interval (95%CI) was 1.051-2.082, P = 0.025] and HDL-C (OR = 0.386, 95%CI was 0.270-0.553, P < 0.001] were independent risk factors of coronary artery disease in elderly patients with AMI. (3) According to the rank score of FBG and HDL-C, the nomogram prediction risk model of aggravating coronary artery disease degree was established for each patient. It was concluded that the risk of coronary artery disease in elderly people with higher FBG level and (or) lower HDL-C level was significantly increased. (4) The nomogram model constructed with the model group data predicted the risk concordance index (C-index) was 0.689, and the C-index of the external validation group was 0.709. CONCLUSIONS: FBG and HDL-C are independent risk factors for aggravating coronary artery disease in elderly patients with AMI. The nomogram model of aggravating coronary artery disease in elderly patients with AMI has good predictive ability, which can provide more intuitive research methods and clinical value for preventing the aggravation of coronary artery disease in elderly patients.

Catalytic asymmetric reductive hydroalkylation of enamides and enecarbamates to chiral aliphatic amines.

To increase the reliability and success rate of drug discovery, efforts have been made to increase the C(sp3) fraction and avoid flat molecules. sp3-Rich enantiopure amines are most frequently encountered as chiral auxiliaries, synthetic intermediates for pharmaceutical agents and bioactive natural products. Streamlined construction of chiral aliphatic amines has long been regarded as a paramount challenge. Mainstream approaches, including hydrogenation of enamines and imines, C-H amination, and alkylation of imines, were applied for the synthesis of chiral amines with circumscribed skeleton structures; typically, the chiral carbon centre was adjacent to an auxiliary aryl or ester group. Herein, we report a mild and general nickel-catalysed asymmetric reductive hydroalkylation to effectively convert enamides and enecarbamates into drug-like α-branched chiral amines and derivatives. This reaction involves the regio- and stereoselective hydrometallation of an enamide or enecarbamate to generate a catalytic amount of enantioenriched alkylnickel intermediate, followed by C-C bond formation via alkyl electrophiles.

Disruption of the lactate dehydrogenase and acetate kinase genes in Klebsiella pneumoniae HD79 to enhance 2,3-butanediol production, and related transcriptomics analysis.

OBJECTIVES: 2,3-Butanediol (2,3-BD) is widely used in several chemical syntheses as well as the manufacture of plastics, solvents, and antifreeze formulations, and can be manufactured by microbial glucose fermentation. Conventional (2,3-BD) fermentation typically has low productivity, yield, and purity, and is expensive for commercial applications. We aimed to delete the lactate dehydrogenase and acetate kinase (ldhA and ack) genes in Klebsiella pneumoniae HD79 by using λRed homologous recombination technology, to eliminate by-products and thereby improve (2,3-BD) production. We also analyzed the resulting gene changes by using transcriptomics. RESULTS: The yield of (2,3-BD) from the mutant Klebsiella strain was 46.21 g/L, the conversion rate was 0.47 g/g, and the productivity was 0.64 g/L·h, which represented increases of 54.9%, 20.5%, and 106.5% respectively, compared to (WT) strains. Lactate and acetate decreased by 48.2% and 62.8%, respectively. Transcriptomics analysis showed that 4628 genes were differentially expressed (404 significantly up-regulated and 162 significantly down-regulated). Moreover, the (2,3-BD) operon genes were differentially expressed. CONCLUSION: Our data showed that the biosynthesis of (2,3-BD) was regulated by inducers (lactate and acetate), a regulator (BudR), and carbon flux. Elimination of acidic by-products by ldhA and ack knockdown significantly improved (2,3-BD) production. Our results provide a deeper understanding of the mechanisms underlying (2,3-BD) production, and form a molecular basis for the improvement this process by genetic modification in the future.

Nickel-Catalyzed Enantioconvergent Reductive Hydroalkylation of Olefins with α-Heteroatom Phosphorus or Sulfur Alkyl Electrophiles.

Substantial advances in enantioconvergent C(sp3)-C(sp3) bond formation reactions have been made in recent years through the use of transition-metal-catalyzed cross-coupling reactions of racemic secondary alkyl electrophiles with organometallic reagents. Herein, we report a general process for the asymmetric construction of alkyl-alkyl bonds adjacent to heteroatoms, namely, a nickel-catalyzed enantioconvergent reductive hydroalkylation of olefins with α-heteroatom phosphorus or sulfur alkyl electrophiles. Including the use of readily available olefins, this reaction has considerable advantages, such as mild reaction conditions, a broad substrate scope, and good functional group compatibility, making it a desirable alternative to traditional electrophile-nucleophile cross-coupling reactions.

miR-125a-5p inhibits the expression of NLRP3 by targeting CCL4 in human vascular smooth muscle cells treated with ox-LDL.

Recent findings have revealed that aberrant miR-125a-5p expression is involved in the development of atherosclerosis. The present study aimed to investigate the precise mechanism of microRNA (miR)-125a-5p in atherosclerosis. Human vascular smooth muscle cells (HVSMCs) were treated with 20 µg/ml oxidized low-density lipoprotein (ox-LDL) for 24 h and were employed as in vitro models of atherosclerosis. Reverse transcription quantitative (RT-qPCR) assays were used to detect miR-125a-5p levels. Immunofluorescence analysis was conducted to assess α-smooth muscle actin (α-SMA) expression. Western blotting and RT-qPCR assays were performed to measure the expression levels of NACHT, LRR and PYD domains-containing protein 3 (NLRP3), apoptosis associated speck-like protein (ASC), caspase-1, active interleukin (IL)-1ß and C-C motif chemokine 4-like (CCL4). Furthermore, the association between miR-125a-5p and CCL4 was assessed using a double luciferase analysis. In addition, VSMCs were transfected with miR-125a-5p mimics (30 nM), miR-125a-5p inhibitor (100 nM) or small interfering RNA against CCL4 (si-CCL4, 50 pM), respectively to further investigate the function of miR-125a-5p in ox-LDL-treated HVSMCs. The present study found that the expression levels of miR-125a-5p were significantly downregulated in HVSMCs, whereas the expression levels of α-SMA, NLRP3, ASC, caspase-1, IL-1ß and CCL4 were markedly upregulated following ox-LDL treatment. Overexpression of miR-125a-5p in the absence of ox-LDL treatment decreased NLRP3, IL-1ß and CCL4 expression, whereas inhibition of miR-125a-5p exhibited the opposite effects. The results of double luciferase analysis confirmed that CCL4 was a direct target of miR-125a-5p. Moreover, transfection of si-CCL4 into HVSMCs significantly decreased the ox-LDL-induced expression of NLRP3, ASC, caspase-1 and IL-1ß proteins. Taken collectively, the results of the present study suggested that miR-125a-5p could negatively regulate the NLRP3 inflammasome by targeting CCL4 in ox-LDL-treated HVSMCs. The data provide new insight to the inhibition of atherosclerosis progression.

Association of early menopause with angiographically-derived SYNTAX score: Observational study.

Association of early menopause with increased risk of cardiovascular events has been confirmed in previous studies. SYNTAX score (SX-score) can comprehensively quantify severity of coronary artery disease (CAD) and predict the outcomes of patients with CAD. However, the association of early menopause with SX-score has never been reported.We prospectively included 1875 consecutive postmenopausal patients who underwent coronary angiography (CAG) and were angiographically diagnosed with CAD from January 2011 to December 2013. SX-score was calculated using the SX-score algorithm based on diagnostic angiogram. Ordinal logistic regression analysis was used to investigate the association between early menopause and SX-score.Patients with early menopause were more likely to have a history of hypertension, diabetes, hyperlipidemia, and less likely to smoking. Besides, they have higher fasting glucose, hemoglobin A1C (HbA1c), total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), and body mass index (BMI) compared with the patients without early menopause. Moreover, patients with early menopause have higher SX-score and multi-vessel diseases. Ordinal logistic regression analysis showed that age, hypertension, diabetes, and early menopause exerted independent influences on SX-score. The patients undergone oophorectomy, early menopause was highly associated with SX-score.Early menopause was an independent predictor of SX-score in postmenopausal patients with CAD.

Abnormal expression of miR­133a in patients with acute myocardial infarction following radical surgery for gastric cancer and the underlying mechanism.

The present study aimed to investigate the expression of microRNA (miR)­133a in patients with or without acute myocardial infarction (AMI) following radical surgery for gastric cancer, and to explore its underlying mechanisms. Blood samples were collected from patients with or without AMI in order to detect the expression levels of miR­133a and endothelial injury markers. In addition, an AMI rat model was established. Reverse transcription­quantitative polymerase chain reaction was used to detect the mRNA expression levels of miR­133a and B­cell lymphoma 2­like 1 (Bcl2l1). In addition, an ELISA assay was used for endothelial injury marker analysis. To investigate the effects of miR­133a on human umbilical vein endothelial cells (HUVECs), a miR­133a inhibitor was used. Cell proliferation and apoptosis were subsequently detected using an MTT assay and flow cytometry. Western blot analysis was also conducted to detect Bcl2l1 protein expression. The results suggested that patients with AMI exhibited significantly increased expression of endothelial injury markers (von Willebrand factor, heart­type fatty acid­binding protein and cardiac troponin I) and miR­133a in blood samples compared with patients without AMI. In addition, treatment with a miR­133a mimic was able to upregulate the expression of endothelial injury markers in an AMI rat model, whereas treatment with a miR­133a inhibitor had the opposite effect. Furthermore, cellular experiments indicated that a miR­133a inhibitor could promote HUVEC proliferation and reduce cell apoptosis. The present results also confirmed that miR­133a directly targets Bcl2l1 and negatively regulates Bcl2l1 expression. In conclusion, the results of the present study suggested that miR­133a was involved in the endothelial injury process after AMI by targeting Bcl2l1.

miRNA­145 inhibits myocardial infarction­induced apoptosis through autophagy via Akt3/mTOR signaling pathway in vitro and in vivo.

The present study investigated the effects of micro (mi)RNA­145 on acute myocardial infarction (AMI) and the potential underlying mechanism. A total of 6 AMI and 6 normal rat tissues were investigated for the present study. It was demonstrated that miRNA­145 expression was downregulated in the AMI rat model, compared with the control group. Downregulation of miRNA­145 increased cardiac cell apoptosis, suppressed phosphorylated (p)­RAC­Î³ serine/threonine­protein kinase (Akt3) and p­mechanistic target of rapamycin (mTOR) protein expression levels and suppressed autophagy in an in vitro model of AMI. However, overexpression of miRNA­145 decreased cardiac cell apoptosis, induced p­Akt3 and p­mTOR protein expression and promoted autophagy in the in vitro model of AMI. The inhibition of Akt3 (GSK2110183, 1 nM) decreased the effect of the miRNA­145 upregulation on cell apoptosis in the in vitro model of AMI. Chloroquine diphosphate (5 µM) inhibited the regulatory effect of miRNA­145 upregulation on autophagy to adjust cell apoptosis, in the in vitro model of AMI. The results of the present study demonstrate that miRNA­145 inhibits myocardial infarction­induced apoptosis via autophagy associated with the Akt3/mTOR signaling pathway in vivo and in vitro.

Weighted gene co­expression network analysis in identification of key genes and networks for ischemic­reperfusion remodeling myocardium.

Acute myocardial infarction induces ventricular remodeling, which is implicated in dilated heart and heart failure. The pathogenical mechanism of myocardium remodeling remains to be elucidated. The aim of the present study was to identify key genes and networks for myocardium remodeling following ischemia­reperfusion (IR). First, the mRNA expression data from the National Center for Biotechnology Information database were downloaded to identify differences in mRNA expression of the IR heart at days 2 and 7. Then, weighted gene co­expression network analysis, hierarchical clustering, protein­protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to identify key genes and networks for the heart remodeling process following IR. A total of 3,321 differentially expressed genes were identified during the heart remodeling process. A total of 6 modules were identified through gene co­expression network analysis. GO and KEGG analysis results suggested that each module represented a different biological function and was associated with different pathways. Finally, hub genes of each module were identified by PPI network construction. The present study revealed that heart remodeling following IR is a complicated process, involving extracellular matrix organization, neural development, apoptosis and energy metabolism. The dysregulated genes, including SRC proto­oncogene, non­receptor tyrosine kinase, discs large MAGUK scaffold protein 1, ATP citrate lyase, RAN, member RAS oncogene family, tumor protein p53, and polo like kinase 2, may be essential for heart remodeling following IR and may be used as potential targets for the inhibition of heart remodeling following acute myocardial infarction.

The anti-inflammatory effect of microRNA-383-3p interacting with IL1R2 against homocysteine-induced endothelial injury in rat coronary arteries.

MicroRNAs (miRs) are widely reported to be novel biomarkers involved in the process of coronary atherosclerosis (CAS). Hence, this study aims to explore the function of miR-383-3p targeting IL1R2 on inflammatory injury of coronary artery endothelial cells (CAECs) in CAS. The underlying regulatory mechanisms of miR-383-3p were analyzed in concert with the treatment of miR-383-3p mimics, miR-383-3p inhibitors, and the combination of miR-383-3p inhibitors and siRNA against IL1R2 in homocysteine (HCY)-induced CAECs. MTT, Hoechst 33258 staining, and tube formation assay were employed in order to measure cell viability, apoptosis, and tube formation, respectively. The levels of IL-1ß, IL-6, IL-10, and IL-18 were determined by ELISA. IL1R2 was verified as the target gene of miR-383-3p by dual-luciferase reporter gene assay. MiR-383-3p was down-regulated in myocardial tissues of AS rats while IL1R2 was the reciprocal. The up-regulation of miR-383-3p decreased the levels of IL1R2, caspase-1, IL-1ß, IL-6, and IL-18 expressions, as well as cell apoptosis rate in the HCY-induced CAECs, while IL-10 expression, cell viability, and tube formation ability were increased. These results were contraindicated in the HCY-induced CAECs treated by miR-383-3p inhibitors. In conclusion, miR-383-3p mediating IL1R2 prevents HCY-induced apoptosis and inflammation injury in CAECs through the inhibition of the activation of inflammasome signaling pathway. These findings highly indicate that miR-383-3p may be beneficial in the prevention of CAS and other cardiovascular diseases.