Efficacy and safety of consolidation durvalumab after chemoradiation therapy for stage III non-small-cell lung cancer: a systematic review, meta-analysis, and meta-regression of real-world studies.

Background: The current review aimed to pool real-world evidence on the efficacy and toxicity of consolidation durvalumab for stage III unresectable non-small cell lung cancer (NSCLC) after curative chemoradiotherapy. Methods: PubMed, CENTRAL, ScienceDirect, Embase, and Google Scholar were searched for observational studies reporting the use of durvalumab for NSCLC till 12th April 2022. Twenty-three studies with 4,400 patients were included. Results: The pooled 1-year overall survival (OS) and progression-free survival rates (PFS) were 85% (95% CI: 81%-89%) and 60% (95% CI: 56%-64%) respectively. Pooled incidence of all-grade pneumonitis, grade ≥3 pneumonitis and discontinuation of durvalumab due to pneumonitis were 27% (95% CI: 19%-36%), 8% (95% CI: 6%-10%) and 17% (95% CI: 12%-23%) respectively. The pooled proportion of patients experiencing endocrine, cutaneous, musculoskeletal, and gastrointestinal adverse events was 11% (95% CI: 7%-18%), 8% (95% CI: 3%-17%), 5% (95% CI: 3%-6%), and 6% (95% CI: 3%-12%), respectively. Conclusion: Meta-regression indicated that performance status significantly influenced PFS, while age, time to durvalumab, and programmed death-ligand 1 status significantly affected pneumonitis rates. Real-world evidence suggests that the short-term efficacy and safety of durvalumab are consistent with that of the PACIFIC trial. The congruence of results lends support to durvalumab use in improving outcomes of unresectable stage III NSCLC. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324663, identifier CRD42022324663.

Preparation of enzyme-responsive composite nanocapsules with sodium carboxymethyl cellulose to improve the control effect of root-knot nematode disease.

Developing an efficient drug delivery system to mitigate the harm caused by root-knot nematodes is crucial. In this study, enzyme-responsive release abamectin nanocapsules (AVB1a NCs) were prepared using 4, 4-diphenylmethane diisocyanate (MDI) and sodium carboxymethyl cellulose as response release factors. The results showed that the average size (D50) of the AVB1a NCs was 352 nm, and the encapsulation efficiency was 92 %. The median lethal concentration (LC50) of AVB1a NCs for Meloidogyne incognita activity was 0.82 mg L-1. Moreover, AVB1a NCs improved the permeability of AVB1a to root-knot nematodes and plant roots and the horizontal and vertical soil mobility. Furthermore, AVB1a NCs greatly reduced the adsorption of AVB1a by the soil compared to AVB1a emulsifiable concentrate (EC), and the effect of the AVB1a NCs on controlling root-knot nematode disease was increased by 36 %. Compared to the AVB1a EC, the pesticide delivery system significantly reduced the acute toxicity to the soil biological earthworms by approximately 16 times that of the AVB1a and had a lower overall impact on the soil microbial communities. This enzyme-responsive pesticide delivery system had a simple preparation method, excellent performance, and high level of safety, and thus has great application potential for plant diseases and insect pests control.

Three-Dimensional Echocardiography and Coagulation Function Detection in the Prognosis Evaluation of Patients with Acute Myocardial Infarction.

This research was aimed at discussing the application value of coagulation function detection and three-dimensional echocardiography in the prognosis evaluation of acute myocardial infarction (AMI) patients. 72 patients with AMI were divided into the recovered group (good recovery) and unrecovered group (poor recovery) according to the results of postoperative ultrasonography. The left ventricular parameters of the patients were detected by three-dimensional ultrasound, and the coagulation function was also detected. The results showed that 3 months after surgery, the regional end-systolic volume (rESV) and regional end-diastolic volume (rEDV) of the left ventricle in the patients were smaller than the measured values 1 week after surgery. The left ventricular regional ejection fraction (rEF) was greater than the value measured 1 week after surgery, and all the differences were statistically significant (P < 0.05). For the end-systolic volume (ESV), end-diastolic volume (EDV), and ejection fraction (EF) (%), the two-dimensional ultrasound results were significantly lower than the three-dimensional ultrasound results, and there were significant differences (P < 0.05). Tmsvle6-Dif% of the recovered patients was 14.99 ± 9.88 and 14.37 ± 9.78 3 months and 6 months after surgery, respectively. These were smaller than 30.91 ± 18.63 and 33.51 ± 17.96 of the unrecovered patients; the differences were of statistical significance (P < 0.05). Tmsvl6-SD% of recovered patients was 3.69 ± 2.47 and 3.61 ± 1.83 3 months and 6 months after surgery, respectively, which were also smaller than 7.38 ± 4.06 and 7.96 ± 2.82 of unrecovered patients, showing statistically significant difference (P < 0.05). The postoperative Tmsvle6-Dif% and Tmsvl6-SD% of the recovered group were lower than those of the unrecovered patients, with the statistically significant differences (P < 0.05). The level of coagulation factors in the recovered group was also significantly lower than that in the unrecovered group with the difference statistically significant (P < 0.05). The results suggested that three-dimensional echocardiography played an important role in the evaluation of cardiac conditions in AMI patients. The level of coagulation factors varied with the AMI condition of patients, and there was an obvious relationship between them, which could provide a reference value for the prognosis evaluation of patients.

Trelagliptin ameliorates oxygen-glucose deprivation/reperfusion (OGD/R)-induced mitochondrial dysfunction and metabolic disturbance of endothelial cells.

Acute myocardial infarction (AMI) is a severe cardiovascular disease with high mortality. It is reported to be closely related to the mitochondrial dysfunction and metabolic disturbance on endothelial cells under a chronic hypoxic state. Significant declined mitochondrial respiration, ATP production, and metabolic changes are the main characteristics of endothelial injury in the disease. Trelagliptin is a DPP-4 inhibitor applied for the treatment of type II diabetes and has been recently reported to exert various pharmacological properties. In this investigation, we examined whether Trelagliptin possessed a protective effect against mitochondrial dysfunction and metabolic disturbance in human aortic valvular endothelial cells (HAVECs) under oxygen-glucose deprivation/reperfusion (OGD/R) conditions. We found that both the cytotoxicity and mitochondrial oxidative stress in HAVECs induced by OGD/R stimulation were greatly alleviated by Trelagliptin. In addition, the declined mitochondrial respiration and ATP production decreased secretion of cystathionine and creatine, and the increased production of triglyceride and adiponectin in OGD/R-challenged HAVECs was dramatically reversed by Trelagliptin, accompanied by the upregulated expression level of PGC-1α and CPT-1. Lastly, the AMPK pathway was observed to be significantly activated in OGD/R-challenged HAVECs by Trelagliptin treatment. After co-administration of the inhibitor of the AMPK pathway, the effects of Trelagliptin on mitochondrial function and metabolic alterations were significantly abolished. Taken together, our data indicate that Trelagliptin ameliorated OGD/R-induced mitochondrial disturbance and metabolic changes by activating the AMPK pathway.

Influence of angiotensin converting enzyme inhibitors/angiotensin receptor blockers on the risk of all-cause mortality and other clinical outcomes in patients with confirmed COVID-19: A systemic review and meta-analysis.

Since the COVID-19 pandemic, physicians concerned about the potential adverse effects of angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs). To explore the relationship between ACEIs/ARBs and the risk of mortality and other clinical outcomes in COVID-19 patients, the authors conducted a systemic review and meta-analysis. An electronic search was performed from inception to November 12, 2020 in PubMed, Medline, EMBASE, ClinicalTrials, TRIP, the Cochrane Library, CNKI, Wanfang, and CBM database. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies of Interventions tool. The primary outcome was in-hospital all-cause mortality. Secondary outcomes included all-cause mortality measured at 30-day or longer term, mechanical ventilation, length of hospital stay, readmission, and cardiac adverse events. A total of 28 studies with 73 465 patients was included. Twenty-two studies with 19 871 patients reported the incidence of all-cause mortality. Results showed no association between using ACEIs/ARBs and risk of mortality crude odds ratio （OR） of 1.02, 95% CI 0.71-1.46, p = .90, I2  = 88%, adjusted OR in 6260 patients of 0.96, 95% CI 0.77-1.18, p = .68, I2  = 0%. While six studies with 10 030 patients reported a lower risk of mortality in ACEIs/ARBs group hazard ratio (HR) of 0.53, 95% CI 0.34-0.84, p = .007, I2  = 68%. Similar association (for HR) was found in hypertension subgroup. There was no significant association for the secondary outcomes. Based on the available data, we concluded that ACEIs/ARBs is not associated with the risk of in-hospital all-cause mortality in COVID-19 patients, but may be associated with a decreased risk of 30-day all-cause mortality. Patients with hypertension may benefit from using ACEIs/ARBs.

Latamoxef induced a severe coagulation disorder in older patients in China: Two case reports.

WHAT IS KNOWN AND OBJECTIVE: We present two cases of severe coagulation disorders induced by latamoxef, thereby revealing risk factors of coagulation disorder in latamoxef-treated patients. CASE SUMMARY: Two very elderly patients developed haemorrhage, and coagulation tests showed a longer prothrombin time (PT), activated partial thromboplastin time (APTT) and a high international normalized ratio (INR). Latamoxef was thought to be responsible for the coagulopathy in these patients, and coagulation disorder was relieved after vitamin-K intake. WHAT IS NEW AND CONCLUSION: We report on two cases of coagulopathy in patients given latamoxef. Advanced age, deficiency in vitamin-K intake, poor nutritional status, abnormal coagulation history, ongoing anti-coagulation/anti-aggregation therapy, renal dysfunction and polypharmacy are possible contributory factors, and should be looked out for when prescribing latamoxef.

Numerical Simulation of Mass-Transfer Characteristics of a Bubble Rising in Yield Stress Fluids.

The mass-transfer characteristics of bubbles rising in yield stress fluids was investigated numerically using volume-of-fluid and user-defined function methods in this study. The CO2 concentration profiles inside the liquid phase near the bubble equator at different bubble diameters, yield stresses, consistency coefficients, and flow indices were observed. The results revealed that the rate of mass transfer decreased with the increase of yield stress, consistency coefficient, and flow index of the liquid phase and the decrease of bubble diameter. Moreover, two empirical correlations for the drag coefficients and Sherwood numbers were developed by introducing one correction factor X for C D correlation and another correction factor f c for Sherwood numbers for correcting the influence of yield stress behavior on bubble motion and mass transfer, respectively. The predictions of the two correlations were compared with the simulated data, and a satisfactory agreement was found.

Discrepant gut microbiota markers for the classification of obesity-related metabolic abnormalities.

The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and investigate their relationships with clinical indicators, 1,914 Chinese adults were enrolled for 16S rRNA gene sequencing in this retrospective study. Based on GM composition, Random forest classifiers were constructed to screen the obesity patients with (Group OA) or without metabolic diseases (Group O) from healthy individuals (Group H), and high accuracies were observed for the discrimination of Group O and Group OA (areas under the receiver operating curve (AUC) equal to 0.68 and 0.76, respectively). Furthermore, six GM markers were shared by obesity patients with various metabolic disorders (Bacteroides, Parabacteroides, Blautia, Alistipes, Romboutsia and Roseburia). As for the discrimination with Group O, Group OA exhibited low accuracy (AUC = 0.57). Nonetheless, GM classifications to distinguish between Group O and the obese patients with specific metabolic abnormalities were not accurate (AUC values from 0.59 to 0.66). Common biomarkers were identified for the obesity patients with high uric acid, high serum lipids and high blood pressure, such as Clostridium XIVa, Bacteroides and Roseburia. A total of 20 genera were associated with multiple significant clinical indicators. For example, Blautia, Romboutsia, Ruminococcus2, Clostridium sensu stricto and Dorea were positively correlated with indicators of bodyweight (including waistline and body mass index) and serum lipids (including low density lipoprotein, triglyceride and total cholesterol). In contrast, the aforementioned clinical indicators were negatively associated with Bacteroides, Roseburia, Butyricicoccus, Alistipes, Parasutterella, Parabacteroides and Clostridium IV. Generally, these biomarkers hold the potential to predict obesity-related metabolic abnormalities, and interventions based on these biomarkers might be beneficial to weight loss and metabolic risk improvement.

Serum miR-599 Serves as a Biomarker for Ischemic Stroke Patients.

BACKGROUND: The current study aims to investigate the expression of miR-599 in serum of patients with ischemic stroke and its correlation with high sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). METHODS: The expression level of miR-24 in serum was detected by real-time PCR, and the expression levels of hs-CRP and MMP-9 were detected by ELISA. Partial correlation analysis was used to explore the correlation be-tween the expression of miR-24 in serum and hs-CRP and MMP-9. ROC analysis was carried out to evaluate the potential diagnostic value. RESULTS: Our data showed that the expression levels of miR-599, hs-CRP, and MMP-9 in serum of the patients were significantly higher than those of the control group (p < 0.05). Partial correlation analysis showed that there was a positive correlation between the expression of miR-599 and hs-CRP and MMP-9 (r = 0.718, p = 0.000; r = 0.658, p = 0.000; r = 0.878, p = 0.000). Meanwhile, serum levels of miR-599, hs-CRP, and MMP-9 in patients with severe neurological deficit were significantly higher than those in patients with moderate and mild neurological deficit (p < 0.05). Moreover, the expression levels of miR-599, hs-CRP, and MMP-9 in serum of patients with dif-ferent degrees of neurological impairment have different correlations. More importantly, ROC analysis demon-strated that combined use of miR-599, hs-CRP, and MMP-9 demonstrated higher diagnostic value for stroke pa-tients. CONCLUSIONS: Serum miR-599 may be used as a molecular marker in the diagnosis of ischemic stroke and may play an important role in the pathogenesis and development of ischemic stroke in cooperation with hs-CRP and MMP-9.

miR­338­3p mediates gluconeogenesis via targeting of PP4R1 in hepatocytes.

Hyperglycaemia is a characteristic of type 2 diabetes. In hepatocytes, impaired insulin sensitivity leads to increased gluconeogenesis and decreased glycogenesis. MicroRNA (miR)­338­3p is associated with tumour necrosis factor (TNF)­α­induced suppression of hepatic glycogenesis via regulation of protein phosphatase 4 regulatory subunit 1 (PP4R1). However, the effect of miR­338­3p on gluconeogenesis in hepatocytes remains unknown. In a previous study, it was demonstrated that miR­338­3p is downregulated in the livers of mice and in mouse HEPA1­6 hepatocytes following treatment with TNF­α. In the present study, the effect of miR­338­3p on TNF­α­induced gluconeogenesis in hepatocytes was investigated. The levels of phosphorylated­FOXO1/FOXO1, phosphoenolpyruvate carboxykinase (PEPCK), peroxisome proliferator­activated receptor γ coactivator (PGC­1α) and glucose­6­phosphatase (G6Pase) were measured by western blotting. The mRNA levels of PEPCK, PGC­1α and G6Pase were determined by quantitative polymerase chain reaction. Pyruvate tolerance testing was used to determine the gluconeogenesis of mouse livers. The results demonstrated that treatment with TNF­α resulted in increased levels of gluconeogenesis in the livers of mice and decreased miR­338­3p expression levels in HEPA1­6 cells. Overexpression of miR­338­3p reversed TNF­α­induced glucose production via enhancement of phosphorylated forkhead box O1 levels and downregulation of the expression levels of genes associated with gluconeogenesis, including peroxisome proliferator­activated receptor γ coactivator­1α, phosphoenolpyruvate carboxykinase and glucose­6­phosphatase. However, inhibition of miR­338­3p expression was revealed to enhance gluconeogenesis in the livers of mice and in HEPA1­6 cells. Furthermore, downregulation of PP4R1 was revealed to attenuate the effect on glucose production following treatment with miR­338­3p inhibitors. In conclusion, the results of the present study revealed that miR­338­3p may be involved in TNF­α­mediated gluconeogenesis via targeting of PP4R1 in hepatocytes.

MiR-19a mediates gluconeogenesis by targeting PTEN in hepatocytes.

As a member of miR-17-92 miRNA clusters, miR­19a has been considered to regulate hepatic glycogenesis by mediating the PI3K/AKT signaling pathway. However, whether miR­19a serves an important role in gluconeogenesis in hepatocytes remains unknown. In the present study, the impact of miR­19a on gluconeogenesis in HEP1­6 cells and its mechanisms of action were investigated. It was observed that overexpression of miR­19a led to decreased glucose production, accompanied by increased activation of the AKT/FOXO1 signaling pathway and downregulated expression of gluconeogenesis­associated genes, including peroxisome proliferator­activated receptor Î³ coactivator 1α, phosphoenolpyruvate carboxykinase and glucose 6­phosphatase in the HEP1­6 cells transfected with the miR­19a mimic. In contrast, suppression of miR­19a impaired the activation of the AKT/FOXO1 signaling pathway and increased the expression of gluconeogenesis­associated genes, accompanied by an elevated glucose production. Additionally, phosphatase and tensin homolog (PTEN) was identified as a target of miR­19a and participated in the miR­19a­mediated gluconeogenesis in hepatocytes. These findings provide mechanistic insight into the effects of miR­19a on the regulation of the AKT/FOXO1 signaling pathway and the expression of gluconeogenesis­associated genes. MiR­19a may mediate gluconeogenesis in hepatocytes by downregulating PTEN expression.

Enforced miR-144-3p Expression as a Non-Invasive Biomarker for the Acute Myeloid Leukemia Patients Mainly by Targeting NRF2.

BACKGROUND: MicroRNAs (miRNAs) are endogenous non-coding RNAs of 19-25 nucleotides in length. Abnormal miRNA expression has been identified in various types of cancer. However, the aberrant expression of miR-1244 has not been reported in acute myeloid leukemia. METHODS: First, the expression of miR-144-3p was explored in the bone marrow and peripheral blood of AML patients and healthy control. Then, we also evaluated the level of miR-144-3p in HL-60 cells. The possible target gene of miR-144-3p was predicted using TargetScan. Dual luciferase reporter assay was applied to validate the target gene of miR-144-3p. Cell viability and apoptosis on miR-144-3p was explored. Western blot analysis was applied to identify the downstream signaling of miR-144-3p. RESULTS: Our data showed that miR-144-3p was markedly increased in both the peripheral blood and bone marrow of AML patients compared with healthy controls. Moreover, we also found an increased expression of miR144-3p in HL-60 cells. In comparison, NRF2 protein expression was significantly decreased in HL-60 cells. Dual luciferase reporter assays demonstrated that miR-144-3p significantly suppressed the relative luciferase reporter activity of a pmirGLO-NRF2-3'UTR. In accordance with the downstream effects of NRF2 overexpression, inhibition of miR-144-3p reduced cell viability and prompted apoptosis. More importantly, we found that the inhibition of miR-144-3p in HL-60 cells could not enhance Caspase-3 activation when NRF2 protein expression was silenced. CONCLUSIONS: These findings suggest a potential oncogenic function of miR-144-3p in HL-60 cells, which is mainly achieved by targeting NRF2.

miR-31 Overexpression Exacerbates Atherosclerosis by Targeting NOX4 in apoE(-/-) Mice.

BACKGROUND: Increasing evidence has shown that microRNAs are involved in apoptosis in different cells. However, the role of miR-31 in atherosclerosis (AS) has never been elucidated. In the present study, we identified the impact of miR-31 on atherosclerosis in macrophages. METHODS: The level of miR-31 in macrophages was examined in apoE-/- mice. Cell viability and apoptosis were examined in macrophage cells transfected with miR-31 mimics, inhibitors or negative control. In addition, the impact of NOX4 on cell apoptosis was tested with a specific siRNA targeting NADPH oxidase 4 (NOX4). RESULTS: An enhanced level of miR-31 was found in macrophage cells of apoE-/- mice, suggesting that miR-31 might contribute to abnormal cell proliferation of macrophage cells. Upregulation of miR-31 decreased cell viability and induced macrophage cell apoptosis. Moreover, knockdown of NOX4 reduced cell migration capacity and enhanced cell apoptosis. CONCLUSIONS: The current data suggested that miR-31 contributed to macrophage apoptosis by regulating the expression of NOX4.

MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation.

Atrial fibrillation (AF) is a highly prevalent arrhythmia with pronounced morbidity and mortality. Inward-rectifier K+ current (IK1) is believed to be an important regulator of reentrant-spiral dynamics and a major component of AF-related electrical remodeling. MicroRNA-26 (miR-26) is predicted to target the gene encoding KIR2.1, KCNJ2. We found that miR-26 was downregulated in atrial samples from AF animals and patients and this downregulation was accompanied by upregulation of IK1/KIR2.1 protein. miR-26 overexpression suppressed expression of KCNJ2/KIR2.1. In contrast, miR-26 knockdown, inhibition, or binding-site mutation enhanced KCNJ2/KIR2.1 expression, establishing KCNJ2 as a miR-26 target. Knockdown of endogenous miR-26 promoted AF in mice, whereas adenovirus-mediated expression of miR-26 reduced AF vulnerability. Kcnj2-specific miR-masks eliminated miR-26-mediated reductions in Kcnj2, abolishing miR-26's protective effects, while coinjection of a Kcnj2-specific miR-mimic prevented miR-26 knockdown-associated AF in mice. Nuclear factor of activated T cells (NFAT), a known actor in AF-associated remodeling, was found to negatively regulate miR-26 transcription. Our results demonstrate that miR-26 controls the expression of KCNJ2 and suggest that this downregulation may promote AF.

miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models.

Recent studies have revealed the critical role of microRNAs (miRNAs) in regulating cardiac injury. Among them, the cardiac enriched microRNA-1(miR-1) has been extensively investigated and proven to be detrimental to cardiac myocytes. However, solid in vivo evidence for the role of miR-1 in cardiac injury is still missing and the potential therapeutic advantages of systemic knockdown of miR-1 expression remained unexplored. In this study, miR-1 transgenic (miR-1 Tg) mice and locked nucleic acid modified oligonucleotide against miR-1 (LNA-antimiR-1) were used to explore the effects of miR-1 on cardiac ischemia/reperfusion injury (30 min ischemia followed by 24 h reperfusion). The cardiac miR-1 level was significantly increased in miR-1 Tg mice, and suppressed in LNA-antimiR-1 treated mice. When subjected to ischemia/reperfusion injury, miR-1 overexpression exacerbated cardiac injury, manifested by increased LDH, CK levels, caspase-3 expression, apoptosis and cardiac infarct area. On the contrary, LNA-antimiR-1 treatment significantly attenuated cardiac ischemia/reperfusion injury. The expression of PKCε and HSP60 was significantly repressed by miR-1 and enhanced by miR-1 knockdown, which may be a molecular mechanism for the role miR-1 in cardiac injury. Moreover, luciferase assay confirmed the direct regulation of miR-1 on protein kinase C epsilon (PKCε) and heat shock protein 60 (HSP60). In summary, this study demonstrated that miR-1 is a causal factor for cardiac injury and systemic LNA-antimiR-1 therapy is effective in ameliorating the problem.

[Expression of SIRT1 in right auricle tissues and the relationship with oxidative stress in patients with atrial fibrillation].

AIM: To observe the expression of mammalian sirtuin 1 (SIRT1) in right auricle tissues in patients presenting with atrial fibrillation (AF) and make clear the relationship between SIRT1 expression and oxidative stress. METHODS: A total of 38 patients with rheumatic heart disease were divided into 2 groups: AF group (AF lasted more than 6 months, n=25) and SR (sinus rhythm) group (n=13). The expression of SIRT1 in right auricle tissues harvested during heart operations was detected by immunohistochemistry. Oxidative stress was estimated by the amounts of malondialdehyde (MDA) and metallothionein (MT) and the activity of superoxide dismutase (SOD) which were detected using thiobarbituric acid reaction (TBA), enzyme-linked immunosorbent assay (ELISA) and xanthine oxidase assay, respectively. RESULTS: Compared with the SR group, the expression of SIRT1 protein in the atrium significantly increased in AF group [P<0.05, (45.8±4.03)% vs (19.7±2.54)%]. In AF group, MDA was (7.24±1.05) nmol/mg, SOD (1034.25±84.32) U/mg and MT (7.21±1.46) µg/g, all being significantly higher than those in SR group[P<0.05, MDA: (3.01±0.47) nmol/mg; SOD: (723.63±65.23) U/mg; MT: (4.31±1.23) µg/g]. Spearman correlation indicated that the expression of SIRT1 had a significantly negative correlation with the amounts of MDA and MT and the activity of SOD (P<0.05, r=-0.447, -0.521, -0.394, respectively). CONCLUSION: The expression of SIRT1 increased in patients with AF. SIRT1 maybe effects the AF by means of inhibiting the process of oxidative stress.

MicroRNA-101 inhibited postinfarct cardiac fibrosis and improved left ventricular compliance via the FBJ osteosarcoma oncogene/transforming growth factor-ß1 pathway.

BACKGROUND: Cardiac interstitial fibrosis is a major cause of the deteriorated performance of the heart in patients with chronic myocardial infarction. MicroRNAs (miRs) have recently been proven to be a novel class of regulators of cardiovascular diseases, including those associated with cardiac fibrosis. This study aimed to explore the role of miR-101 in cardiac fibrosis and the underlying mechanisms. METHODS AND RESULTS: Four weeks after coronary artery ligation of rats, the expression of miR-101a and miR-101b (miR-101a/b) in the peri-infarct area was decreased. Treatment of cultured rat neonatal cardiac fibroblasts with angiotensin II also suppressed the expression of miR-101a/b. Forced expression of miR-101a/b suppressed the proliferation and collagen production in rat neonatal cardiac fibroblasts, as revealed by cell counting, MTT assay, and quantitative reverse transcription-polymerase chain reaction. The effect was abrogated by cotransfection with AMO-101a/b, the antisense inhibitors of miR-101a/b. c-Fos was found to be a target of miR-101a because overexpression of miR-101a decreased the protein and mRNA levels of c-Fos and its downstream protein transforming growth factor-ß1. Silencing c-Fos by siRNA mimicked the antifibrotic action of miR-101a, whereas forced expression of c-Fos protein canceled the effect of miR-101a in cultured cardiac fibroblasts. Strikingly, echocardiography and hemodynamic measurements indicated remarkable improvement of the cardiac performance 4 weeks after adenovirus-mediated overexpression of miR-101a in rats with chronic myocardial infarction. Furthermore, the interstitial fibrosis was alleviated and the expression of c-Fos and transforming growth factor-ß1 was inhibited. CONCLUSION: Overexpression of miR-101a can mitigate interstitial fibrosis and the deterioration of cardiac performance in postinfarct rats, indicating the therapeutic potential of miR-101a for cardiac disease associated with fibrosis.