Bovine Colostrum miR-30a-5p Targets the NF-κB Signaling Pathway to Alleviate Inflammation in Intestinal Epithelial Cells.

Inflammatory bowel disease (IBD) is a common disease of the digestive system, and an excessive immune response mediated by the nuclear factor κ-B (NF-κB) signaling pathway is an essential etiology. Recent studies have found that bovine milk exosomes can improve intestinal mucosal health by delivering microRNA (miRNA), but the mechanism of action is so far unknown. In the present study, we analyzed the differential expression profiles of miRNA in colostrum and mature milk exosomes using high-throughput sequencing, based on the demonstration that colostrum exosomes inhibit the lipopolysaccharide (LPS)-induced intestinal epithelial NF-κB inflammatory pathway better than mature milk exosomes. The bta-miR-30a-5p, which is specifically highly expressed in colostrum, was screened, and its predicted target gene TRAM was found to be closely related to the NF-κB signaling pathway by functional enrichment analysis. Further, we used gene overexpression and silencing techniques and found that the bta-miR-30a-5p transfection treatment was confirmed to inhibit LPS-induced NF-κB signaling pathway activation and downstream pro-inflammatory factor expression, while the expression of its potential target gene, TRAM, was also suppressed. It is hypothesized that the high expression of bta-miR-30a-5p in colostrum, which targets TRAM to inhibit the downstream NF-κB inflammatory pathway, may be one of the molecular mechanisms responsible for its superior effect on resisting inflammatory attack compared to mature milk.

Revascularization for Patients With Heart Failure With Preserved Ejection Fraction and Coronary Artery Disease.

Coronary artery disease (CAD) is one of the main causes of heart failure (HF) with preserved ejection fraction (HFpEF). The efficacy of revascularization therapy in patients with HFpEF and CAD, however, remains unclear. Patients who underwent coronary angiography from January 2017 to December 2019 were included in this retrospective study if they further satisfied the diagnosis of HFpEF (left ventricular ejection fraction ≥50% plus plasma N-terminal pro-BNP ≥125 pg/ml) and CAD (patients had a history of confirmed myocardial infarction or ≥50% stenosis in at least 1 epicardial coronary vessel). Clinical data, way of revascularization, and outcome events (unplanned repeated revascularization, HF readmission, cardiovascular death, readmission of cerebral hemorrhage/stroke or gastrointestinal bleeding, and all-cause death) were recorded and analyzed. A total of 1,111 patients were enrolled for the present analysis. Based on whether the revascularization was complete or not, the patients were divided into the complete revascularization group (n = 780) and the incomplete/no revascularization group (n = 331). All patients were followed up with a median of 355 days. The overall rates of unplanned repeated revascularization, HF readmission, and cardiovascular death were 6.6%, 5.0%, and 0.4%, respectively. Compared with incompletely/not revascularized patients, completely revascularized patients had a lower rate of unplanned repeated revascularization (10.9% vs 4.7%, p <0.001) and cardiovascular death (0.9% vs 0.1%, p = 0.048). However, HF readmission, readmission of cerebral hemorrhage/stroke or gastrointestinal bleeding, and noncardiac death were comparable between the 2 groups. The regression analysis showed that hyperlipidemia, previous myocardial infarction, in-stent restenosis, and way of revascularization were associated with the composite events of unplanned repeated revascularization, HF readmission, and cardiovascular death during the follow-up. Complete revascularization may reduce unplanned repeated revascularization and cardiovascular death for patients with HFpEF and CAD.

Tibetan Plateau yak milk: A comprehensive review of nutritional values, health benefits, and processing technology.

Yak milk is a characteristic animal product of yaks in the Qinghai-Tibet Plateau. Although yak milk production is low, it is richer in nutrients such as protein, fat, and lactose, a more comprehensive range of bioactive components, and unique microbial resources than Holstein cow milk. The plateau environment makes yak milk resistant to hypoxia, anti-fatigue, antioxidant, antibacterial, and relieves chronic diseases. In this paper, based on the systematic analysis of yak milk research results in the past 20 years using CiteSpace 6.1.R2, we reviewed yak lactation performance and nutritional efficacy of yak milk. This paper summarizes the improvement of traditional yak dairy processing technology, and also focuses on the microbial diversity of yak milk sources and their beneficial effects. The purpose of this review is to provide scientific support for the development of a quality yak milk industry on the Tibetan plateau.

Effects of Freezing Raw Yak Milk on the Fermentation Performance and Storage Quality of Yogurt.

In this study, the effects of freezing yak milk at -20 °C and -40 °C for 30, 90 and 180 days on the fermentation characteristics and storage quality of the corresponding yogurt were discussed. The results showed that, compared with that of yogurt made from fresh yak milk, the lactic acid bacteria (LAB) growth and acid production rate of the yogurt in the -20 °C group decreased at 90 d. The water-holding capacity, viscosity and hardness decreased during storage, and a sour taste was prominent, while no significant changes were observed in the -40 °C group. At 180 d of freezing, the post-acidification of the yogurt in the -20 °C and -40 °C groups increased after 21 d of storage. Compared with the -40 °C group, the -20 °C group showed a significant decrease in LAB counts, a decrease in pH value to 3.63-3.80 and poor texture and sensory quality.

Dairy products and constituents: a review of their effects on obesity and related metabolic diseases.

Obesity has become a global public health problem that seriously affects the quality of life. As an important part of human diet, dairy products contain a large number of nutrients that are essential for maintaining human health, such as proteins, peptides, lipids, vitamins, and minerals. A growing number of epidemiological investigations provide strong evidence on dairy interventions for weight loss in overweight/obese populations. Therefore, this paper outlines the relationship between the consumption of different dairy products and obesity and related metabolic diseases. In addition, we dive into the mechanisms related to the regulation of glucose and lipid metabolism by functional components in dairy products and the interaction with gut microbes. Lastly, the role of dairy products on obesity of children and adolescents is revisited. We conclude that whole dairy products exert more beneficial effect than single milk constituent on alleviating obesity and that dairy matrix has important implications for metabolic health.

Advances in Low-Lactose/Lactose-Free Dairy Products and Their Production.

With increasing health awareness worldwide, lactose intolerance has become a major concern of consumers, creating new market opportunities for low-lactose/lactose-free dairy foods. In recent years, through innovating processes and technologies, dairy manufacturers have significantly improved the variety, and functional and sensory qualities of low-lactose and lactose-free dairy products. Based on this, this paper first covers the pathology and epidemiology of lactose intolerance and market trends. Then, we focus on current advantages and disadvantages of different lactose hydrolysis technologies and improvements in these technologies to enhance nutritional value, and functional, sensory, and quality properties of lactose-free dairy products. We found that more and more cutting-edge technologies are being applied to the production of lactose-free dairy products, and that these technologies greatly improve the quality and production efficiency of lactose-free dairy products. Hopefully, our review can provide a theoretical basis for the marketing expansion and consumption guidance for low-lactose/lactose-free dairy products.

Different expression and prognostic value of troponin in ischemic cardiomyopathy and non-ischemic dilated cardiomyopathy.

BACKGROUND: Early risk stratification of patients with ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (NIDCM) may be beneficial for therapies. METHODS: We retrospectively enrolled all patients admitted for acute heart failure (HF) between January 2019 and December 2021 in Zhongshan Hospital Fudan University, dividing them according to etiology (ICM or NIDCM). Cardiac troponin T (TNT) concentration was compared between two groups. Risk factors for positive TNT and in-hospital all-cause mortality were investigated with regression analysis. RESULTS: A total of 1525 HF patients were enrolled, including 571 ICM and 954 NIDCM. The TNT positive patients were not different between the two groups (41.3% in ICM group vs. 37.8% in NIDCM group, P = 0.215). However, the TNT value in ICM group were significantly higher than that in NIDCM group (0.025 (0.015-0.053) vs. 0.020 (0.014-0.041), P = 0.001). NT-proBNP was independently associated with TNT in both ICM and NIDCM group. Although the in-hospital all-cause mortality did not show much difference between the two groups (1.1% vs. 1.9%, P = 0.204), the NIDCM diagnosis was associated with reduced risk of mortality after multiple adjustments (OR 0.169, 95% CI 0.040-0.718, P = 0.016). Other independent risk factors included the level of NT-proBNP (OR 8.260, 95% CI 3.168-21.533, P < 0.001), TNT (OR 8.118, 95% CI 3.205-20.562, P < 0.001), and anemia (OR 0.954, 95% CI 0.931-0.978, P < 0.001). The predictive value of TNT and NT-proBNP for all-cause mortality was similar. However, the best cutoff values of TNT for mortality were different between ICM and NIDCM groups, which were 0.113 ng/mL and 0.048 ng/mL, respectively. CONCLUSION: The TNT level was higher in ICM patient than that in NIDCM patients. TNT was an independent risk factor for in-hospital all-cause mortality for both ICM and NIDCM patients, although the best cutoff value was higher in ICM patients.

Advances in the protection of intestinal mucosal barrier function by milk-derived miRNAs.

Milk is a significant component of the human diet, providing an abundance of energy and nutrients and a variety of functional factors. Recent studies have revealed that milk is highly enriched in exosomes with intercellular communication functions, which can act on target cells in vivo by carrying and delivering miRNAs and critically participating in physiological processes such as host intestinal development, cell differentiation, and immune response. In recent years, the biosynthesis of milk-derived miRNAs and their cross-border uptake mechanisms, the biological functions of milk-derived miRNAs and the universality of their regulatory modalities, the extraction and identification of milk-derived miRNAs as novel active ingredients and their potential as biomarkers have been extensively studied. Accordingly, this paper compares and summarizes the cutting-edge research on the nutritional and health functions of milk-derived miRNAs, including the types and contents of milk-derived miRNAs, their transportability and stability in the digestive tract, with special attention to the molecular mechanisms of the milk-derived miRNAs in protecting the barrier function of the intestinal mucosa, and looks forward to the application of milk-derived miRNAs as novel dietary supplements in infant foods and functional foods. It will inform future efforts to elucidate the profound impact of milk-derived miRNAs on the human intestine and broader health.

SmileGNN: Drug-Drug Interaction Prediction Based on the SMILES and Graph Neural Network.

Concurrent use of multiple drugs can lead to unexpected adverse drug reactions. The interaction between drugs can be confirmed by routine in vitro and clinical trials. However, it is difficult to test the drug-drug interactions widely and effectively before the drugs enter the market. Therefore, the prediction of drug-drug interactions has become one of the research priorities in the biomedical field. In recent years, researchers have been using deep learning to predict drug-drug interactions by exploiting drug structural features and graph theory, and have achieved a series of achievements. A drug-drug interaction prediction model SmileGNN is proposed in this paper, which can be characterized by aggregating the structural features of drugs constructed by SMILES data and the topological features of drugs in knowledge graphs obtained by graph neural networks. The experimental results show that the model proposed in this paper combines a variety of data sources and has a better prediction performance compared with existing prediction models of drug-drug interactions. Five out of the top ten predicted new drug-drug interactions are verified from the latest database, which proves the credibility of SmileGNN.

2'-Fucosyllactose promotes Lactobacillus rhamnosus KLDS 8001 to repair LPS-induced damage in Caco-2 cells.

The aim of this study was to investigate the effect of 2'-fucosyllactose (2'-FL) on the repair of monolayer barrier damage in Caco-2 cells by Lactobacillus rhamnosus KLDS 8001 (KLDS 8001). The results showed that the addition of 2'-FL not only promoted the adhesion ability of KLDS 8001 to Caco-2 cells but also improved the anti-adhesive effect of pathogenic bacteria. Compared with 2'-FL or KLDS 8001 alone, 2'-FL+KLDS 8001 significantly reduced lipopolysaccharide (LPS)-induced malondialdehyde (MDA), lactate dehydrogenase (LDH) release, and cytokine (IL-1ß, IL-6, and TNF-α) production. In addition, 2'-FL effectively promoted the transmembrane electrical resistance (TEER), cell viability, and cellular permeability of KLDS 8001 repaired damaged cells with dose-dependent properties. The mRNA and protein expression of Zonula Occludens-1 (ZO-1), Occludin, and Claudin-1 were also upregulated in the KLDS 8001 and 2'-FL co-treated treatment group. It was speculated that 2'-FL could effectively regulate the interaction between KLDS 8001 and intestinal epithelial cells to play a role in maintaining intestinal barrier function and avoiding pathogenic bacteria invasion. PRACTICAL APPLICATIONS: As the most widely used human milk oligosaccharides (HMOs), 2'-FL is vital for maintaining infant intestinal health. Our study found that the addition of 2'-FL promoted KLDS 8001 adhesion, anti-adhesion of pathogenic bacteria, anti-inflammatory capacity, repair of barrier damage, and tight junction protein expression, providing a new strategy to protect infant intestinal health and prevent various intestinal diseases.

Qiliqiangxin alleviates Ang II-induced CMECs apoptosis by downregulating autophagy via the ErbB2-AKT-FoxO3a axis.

Our previous work revealed the protective effect of Qiliqiangxin (QLQX) on cardiac microvascular endothelial cells (CMECs), but the underlying mechanisms remain unclear. We aimed to investigate whether QLQX exerts its protective effect against high-concentration angiotensin II (Ang II)-induced CMEC apoptosis through the autophagy machinery. CMECs were cultured in high-concentration Ang II (1 µM) medium in the presence or absence of QLQX for 48 h. We found that QLQX obviously inhibited Ang II-triggered autophagosome synthesis and apoptosis in cultured CMECs. QLQX-mediated protection against Ang II-induced CMEC apoptosis was reversed by the autophagy activator rapamycin. Specifically, deletion of ATG7 in cultured CMECs indicated a detrimental role of autophagy in Ang II-induced CMEC apoptosis. QLQX reversed Ang II-mediated ErbB2 phosphorylation impairment. Furthermore, inhibition of ErbB2 phosphorylation with lapatinib in CMECs revealed that QLQX-induced downregulation of Ang II-activated autophagy and apoptosis was ErbB2 phosphorylation-dependent via the AKT-FoxO3a axis. Activation of ErbB2 phosphorylation by Neuregulin-1ß achieved a similar CMEC-protective effect as QLQX in high-concentration Ang II medium, and this effect was also abolished by autophagy activation. These results show that the CMEC-protective effect of QLQX under high-concentration Ang II conditions could be partly attributable to QLQX-mediated ErbB2 phosphorylation-dependent downregulation of autophagy via the AKT-FoxO3a axis.

Association of Small Intestinal Bacterial Overgrowth With Heart Failure and Its Prediction for Short-Term Outcomes.

Background Small intestinal bacterial overgrowth (SIBO) is a common pathological condition of intestinal microbiota. The prevalence of SIBO and its prognostic value in patients with heart failure (HF) are unknown. Methods and Results A total of 287 patients tested for SIBO using lactulose hydrogen-methane breath test were evaluated. At least 1 of the following criteria fulfilled was SIBO positive: patients with fasting hydrogen level ≥20 parts per million (ppm) or a ≥20 ppm rise in hydrogen by 90 minutes were diagnosed with SIBO (H2) positive; and patients with methane levels ≥10 ppm at any test point were diagnosed with SIBO (CH4) positive. The association between SIBO and the composite of cardiovascular death and HF rehospitalization was investigated. In 287 consecutive patients with HF, 128 (45%) were positive for SIBO. Our result showed SIBO increased the risk of HF rehospitalization in patients with HF with reduced ejection fraction (P<0.001), and the risk of cardiovascular death in patients with HF with preserved EF (P=0.011). SIBO was an independent risk factor of primary end point in patients with HF (hazard ratio [HR], 2.13; 95% CI; 1.26-3.58; P=0.005). In addition, SIBO (CH4) showed a prognostic value on adverse outcomes (HR, 2.35; 95% CI, 1.38-4.02; P<0.001), whereas the association between SIBO (H2) and outcomes was not statistically significant. Conclusions There was high prevalence of SIBO in patients with HF, and SIBO was independently associated with poor outcomes. Proactive treatment for SIBO may provide extra benefit for patients with HF.

Qiliqiangxin Prescription Promotes Angiogenesis of Hypoxic Primary Rat Cardiac Microvascular Endothelial Cells via Regulating miR-21 Signaling.

BACKGROUND AND OBJECTIVE: Angiogenesis is the most important repair process of tissues subjected to ischemic injury. The present study aims to investigate whether the pro-angiogenic effect of Qiliqiangxin prescription (QL) is mediated through miR-21 signaling. METHODS: Cardiac microvascular endothelial cells (CMECs) were isolated and cultured from 2-3 weeks old SD rats by the method of planting myocardium tissues. The purity was identified by CD31 immunofluorescence staining. CMECs were then cultured under 1% O2 hypoxia or normoxia condition for 24h in the presence or absence of QL pretreatment (QL, 0.5mg/ml, 24h). The mimics and inhibitors of miR-21 were transfected into CMECs. miR-21, HIF-1α, and VEGF expressions of CMECs were then detected by qRT-PCR and/or Western blot. The proliferation, migration, and tube formation functions of CMECs were assessed using the BrdU assay, wound healing test, and tube formation assay, respectively. RESULTS: The results showed that compared with the control group, hypoxia significantly upregulated the expression of miR-21 and impaired CMECs proliferation, migration, and tube formation functions. Compared with the hypoxia group, QL further upregulated miR-21, HIF-1α, and VEGF expressions, and improved cell proliferation, migration, and tube formation of hypoxic CMECs. These effects of QL were abolished by a knockdown of miR-21. Conversely, treatment with miR-21 mimics further enhanced QL induced changes in hypoxic CMECs. CONCLUSION: Results indicate that the pro-angiogenesis effects of QL on hypoxic CMECs are mediated by activating miR-21 and its downstream HIF-1α/VEGF pathway possibly.

Adaptive Autophagy Offers Cardiorenal Protection in Rats with Acute Myocardial Infarction.

OBJECTIVE: Understanding the multifactorial changes involved in the kidney and heart after acute myocardial infarction (AMI) is prerequisite for further mechanisms and early intervention, especially autophagy changes. Here, we discussed the role of adaptive autophagy in the heart and kidney of rats with AMI. METHODS: A rat model of AMI was established by ligating the left anterior descending branch of the coronary artery. Animals were sacrificed at 2 and 4 weeks after the operation to assess the morphological and functional changes of the heart and kidney, as well as the autophagy pathway. In vitro, HK-2 and AC16 cell injuries and the autophagy pathway were assayed after autophagy was inhibited by 3-methyladenine (3-MA) in a hypoxia incubator. RESULTS: We found that the left ventricular systolic pressure (LVSP) significantly decreased in the model group at weeks 2 and 4. At weeks 2 and 4, the level of urinary kidney injury molecule 1 (uKIM1) of the model group was significantly higher than the sham group. At week 4, urinary neutrophil gelatinase-associated lipocalcin (uNGAL) and urinary albumin also significantly increased. At week 2, microtubule-associated protein 1 light chain 3-II (LC3-II), ATG5, and Beclin1 were significantly elevated in the heart and kidney compared with the sham-operated rats, but there was no change in p62 levels. At week 4, LC3-II did not significantly increase and p62 levels significantly increased. In addition, 3-MA markedly increased KIM1, NGAL, and the activity of caspase-3 in the hypoxic HK-2 and AC16 cell. CONCLUSION: Autophagy will undergo adaptive changes and play a protective role in the heart and kidney of rats after AMI.

Qiliqiangxin Improves Cardiac Function through Regulating Energy Metabolism via HIF-1α-Dependent and Independent Mechanisms in Heart Failure Rats after Acute Myocardial Infarction.

The present study is aimed at investigating whether Qiliqiangxin (QL) could regulate myocardial energy metabolism in heart failure rats after acute myocardial infarction (AMI) and further exploring the underlying mechanisms. AMI was established by ligating the left anterior descending coronary artery in adult male SD rats. AMI rats with ejection fraction (EF) < 50% at two weeks after the operation were chosen as heart failure rats for the main study. Rats were randomized into the sham, MI, MI+QL, and MI+QL+2-MeOE2 groups. The results showed that compared with the MI group, QL significantly improved cardiac function, reduced serum NT-proBNP level, and alleviated myocardial fibrosis. QL also increased myocardial capillary density by upregulated protein expressions of vascular endothelial growth factor (VEGF) and CD31 by regulating the HIF-1α/VEGF pathway. Moreover, QL promoted ATP production, glucose uptake, and glycolysis by upregulating HIF-1α and a series of glycolysis-relevant enzymes in a HIF-1α-dependent manner. QL also improved myocardial glucose oxidation enzyme expression and free fatty acid uptake by a HIF-1α-independent pathway. Our results indicate that QL treatment improves cardiac function through regulating glucose uptake, FFA uptake, and key enzymes of energy metabolism via HIF-1α-dependent and independent mechanisms.

Asymmetric transmission of light waves in a photonic crystal waveguide heterostructure with complete bandgaps.

Here, we theoretically present an on-chip nanophotonic asymmetric transmission device (ATD) based on the photonic crystal (PhC) waveguide structure with complete photonic bandgaps (CPBGs). The ATD comprises two-dimensional silica and germanium PhCs with CPBGs, within which line defects are introduced to create highly efficient waveguides to achieve high forward transmittance. In the meantime, the total internal reflection principle is applied to block the backward incidence, achieving asymmetric transmission. We optimize the design of the PhCs and the waveguide structure by scanning different structure parameters. The optimized ATD shows a high forward transmittance of 0.581 and contrast ratio of 0.989 at the wavelength of 1582 nm for TE mode. The results deepen the understanding and open up the new possibility in designing novel ATDs. The on-chip ATD will find broad applications in optical communications and quantum computing.

Cordyceps cicadae Prevents Renal Tubular Epithelial Cell Apoptosis by Regulating the SIRT1/p53 Pathway in Hypertensive Renal Injury.

Hypertensive renal injury is a primary etiology of end-stage renal disease, and satisfactory therapeutic strategies are urgently required. Cordyceps cicadae, a traditional Chinese herb, has potential renoprotective benefits and is widely used in the treatment of many kidney diseases. To investigate the mechanisms underlying the renoprotective effect of C. cicadae on hypertensive renal injury, we studied the effect of C. cicadae on tubular epithelial cells (TECs) in a spontaneously hypertensive rat (SHR) model and angiotensin II- (AngII-) cultured primary TECs. Our study showed that C. cicadae treatment could decrease 24-hour urine albumin, albumin-to-creatinine ratio (ACR), ß2-MG level, and kidney injury molecule-1 (kim-1) level in SHR urine, alleviate interstitial fibrosis, and reduce α-smooth muscle actin (α-SMA) expression in SHR kidney. In primary TECs, medicated serum containing C. cicadae (CSM) might significantly reduce the AngII-induced production of kim-1 and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, C. cicadae treatment could decrease TEC apoptosis in SHRs as assessed by the terminal transferase-mediated biotin dUTP nick-end labeling (TUNEL) assay. CSM could inhibit caspase-3 activity and enhance cellular viability as measured by methyl thiazolyl tetrazolium in AngII-cultured TECs, suggesting that CSM might reduce the apoptosis level in TECs induced by AngII. We found that the SIRT1 expression level was markedly lowered, while the protein level of acetylated-p53 was elevated in the TECs of patients with hypertensive renal injury and SHRs. C. cicadae presented the effect of regulating the SIRT1/p53 pathway. Further SIRT1 inhibition with EX527 reversed the effect of C. cicadae on AngII-induced apoptosis. Taken together, our results indicate that C. cicadae offers a protective effect on TECs under hypertensive conditions, which may be related to its antiapoptotic effect through regulation of the SIRT1/p53 pathway.

Prognostic value of sST2 in patients with heart failure with reduced, mid-range and preserved ejection fraction.

BACKGROUNDS: Prognostic value of soluble suppression of tumorigenecity (sST2), a novel circulating biomarker for myocardial fibrosis, remains elusive in the heart failure patients with preserved ejection fraction (HFpEF). METHODS: 405 consecutive patients with heart failure (HF) were enrolled prospectively, and were grouped into HF with reduced ejection fraction (HFrEF, N = 215), HF with mid-range ejection fraction (HFmrEF, N = 80) and HFpEF (N = 110). The primary endpoint was the composite endpoint of all-cause death and HF rehospitalization. RESULTS: After a median of 12 months, 139 patients reached the primary endpoint, with 57 patients died and 82 patients rehospitalized. Multivariate analysis confirmed that sST2 was an independent risk factor of the primary endpoint for all HF patients [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.30-4.22, P = 0.004]. Predicting efficacy of sST2 on outcomes was higher for HFpEF (HR 6.48, 95%CI 1.89-22.21, P = 0.003) as compared to HFrEF (HR 3.21, 95% CI 1.67-6.19, P = 0.000). But the association between sST2 and outcomes in HFmrEF is not statistical (HR 3.38, 95%CI 0.82-13.86, P = 0.091). The combined use of sST2 and N terminal pro B type natriuretic peptide (NT-proBNP) could improve the prognostic value compared to using NT-proBNP alone in HFrEF (AUC = 0.794 vs. 0.752, P = 0.034). CONCLUSION: Higher baseline sST2 levels are associated with increased risk of all-cause death and HF rehospitalization in patients with HF independent of ejection fraction. The combined use of sST2 and NT-proBNP could improve the prognostic value than using these two values alone, especially for HFrEF patients.

Diffuse myocardial fibrosis and the prognosis of heart failure with reduced ejection fraction in Chinese patients: a cohort study.

Evidence regarding the relationship between diffuse myocardial fibrosis and the prognosis of heart failure with reduced ejection fraction (HFrEF) was limited. Therefore, this study set out to investigate whether diffuse myocardial fibrosis was independently related to the prognosis of failure with reduced ejection fraction in Chinese patients after adjusting for other covariates. The present study was a cohort study. A total of 45 consecutive HFrEF patients were involved in Zhongshan Hospital of Fudan University in China from 1/9/2015 to 31/12/2016. The target-independent variable was extracellular volume (ECV) quantified by cardiac magnetic resonance T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence at baseline. To assess the prognostic impact of MOLLI-ECV, its association with hospitalization for heart failure/cardiac death was tested by multivariable Cox regression analysis. Covariates involved in this study included age, gender, body mass index, heart rate, systolic blood pressure diastolic blood pressure, smoking, hypertension, diabetes mellitus, etiology, NYHA functional class, blood urea nitrogen, creatinine, serum uric acid, total bilirubin, and growth stimulation-expressed gene 2. Ten age- and sex-matched healthy participants with no history of cardiovascular disease served as a control group. Mean MOLLI-ECV was significantly higher in HFrEF patients versus healthy controls (29.55 ± 1.46% vs. 23.17 ± 1.93%, P < 0.001). Patients were followed for 9 months, during which the primary outcome (cardiac death or first heart failure hospitalization) occurred in 15 patients. By Kaplan-Meier analysis, patients with high MOLLI-ECV ≥ 30.10% had shorter event-free survival than the middle (MOLLI-ECV between 30.10 and 28.60) and low (MOLLI-ECV < 28.60) MOLLI-ECV patients (log-rank, P = 0.0035). Result of fully-adjusted multivariable Cox regression analysis showed MOLLI-ECV was positively associated with the composite outcome of HFrEF patients after adjusting confounders hazard ratio (HR) 2.57, 95% CI (1.09, 6.04). By subgroup analysis, a stronger association was seen in patients who with NYHA functional class III-IV, hematocrit < 39.8%, left atrial diameter ≥ 53.5 mm, or without the medical history of MRA or diuretics other than MRA. The P for interaction was < 0.05. In HFrEF patients, the relationship between MOLLI-ECV determined by CMR and the composite outcome is linear. High MOLLI-ECV was associated with a higher rate of cardiac mortality and first HF hospitalization in the short term follow up.

Effects of Adiponectin on Diastolic Function in Mice Underwent Transverse Aorta Constriction.

Diastolic dysfunction is common in various cardiovascular diseases, which could be affected by adiponectin (APN). Nevertheless, the effects of APN on diastolic dysfunction in pressure overload model induced by transverse aorta constriction (TAC) remain to be further elucidated. Here, we demonstrated that treatment of APN attenuated diastolic dysfunction and cardiac hypertrophy in TAC mice. Notably, APN also improved active relaxation of adult cardiomyocytes, increased N2BA/N2B ratios of titin isoform, and reduced collagen type I to type III ratio and lysyl oxidase (Lox) expressions in the myocardial tissue. Moreover, APN supplementation suppressed TAC-induced oxidative stress. In vitro, inhibition of AMPK by compound C (Cpc) abrogated the effect of APN on modulation of titin isoform shift and the anti-hypertrophic effect of APN on cardiomyocytes induced by AngII. In summary, our findings indicate that APN could attenuate diastolic dysfunction in TAC mice, which are at least partially mediated by AMPK pathway.