Exploring the role and mechanism of hyperoside against cardiomyocyte injury in mice with myocardial infarction based on JAK2/STAT3 signaling pathway.

BACKGROUND: Myocardial infarction (MI) is one of the most deadly diseases in the world. Hyperoside (Hyp) has been shown to have a protective effect on cardiovascular function through various signaling pathways, but whether it can protect myocardial infarction by regulating JAK2/STAT3 signaling pathway is unknown. AIM OF THE STUDY: To investigate whether Hyp could protect the heart against myocardial infarction injury in mice by modulating JAK2/STAT3 signaling pathway and its potential mechanism. METHODS: In vivo experiments, the myocardial infarction model was established by ligating the left anterior descending coronary artery (LAD) of male C57BL/6 mice permanently. The mice were divided into seven groups: sham group, MI group, MI+Hyp (9 mg/kg), MI+Hyp (18 mg/kg) group, MI+Hyp (36 mg/kg) group, MI+Captopril group (15 mg/kg) group and MI+Hyp (36 mg/kg)+AG490 (7.5 mg/kg) group. Each group of animals were given different concentrations of hyperoside, positive control drug or inhibitor of JAK2/STAT3 singaling. After 14 days of administration, the electrocardiogram (ECG), echocardiography and serum myocardial injury markers were examined; Slices of mouse myocardial tissue were assessed for histopathological changes by HE, Masson and Sirius Red staining. TTC and TUNEL staining were used to evaluate the myocardial infarction area and cardiomyocytes apoptosis respectively. The expression of JAK2/STAT3 signaling pathway, apoptosis and autophagy-related proteins were detected by western blot. In vitro experiments, rat H9c2 cardiomyocytes were deprived of oxygen and glucose (OGD) to stimulate myocardial ischemia. The experiment was divided into seven groups: Control group, OGD group, OGD+Hyp (20 µM) group, OGD+Hyp (40 µM) group, OGD+Hyp (80 µM), OGD+Captopril (10 µM) group and OGD+Hyp (80 µM)+AG490 (100 µM) group. Myocardial cell damage and redox index were measured 12 h after OGD treatment. ROS content in cardiomyocytes was detected by immunofluorescence. Cardiomyocytes apoptosis was detected by flow cytometry. The expressions of JAK2/STAT3 signaling pathway-related proteins, apoptosis and autophagy related proteins were detected by western blot. RESULTS: In vivo, hyperoside could ameolirate ECG abnormality, increase cardiac function, reduce myocardial infarction size and significantly reduce myocardial fibrosis level and oxidation level. The experimental results in vitro showed that Hyp could reduce the ROS content in cardiomyocytes, decrease the level of oxidative stress and counteract the apoptosis induced by OGD injury . Both in vivo and in vitro experiments showed that hyperoside could increase phosphorylated JAK2 and STAT3, indicating that hyperoside could play a cardioprotective role by activating JAK2/STAT3 signaling pathway. It was also shown that hyperoside could increase the autophagy level of cardiomyocytes in vivo and in vitro. However the cardiomyocyte-protective effect of Hyp was abolished in combination with JAK2/ STAT3 signaling pathway inhibitor AG490. These results indicated that the protective effect of Hyp on cardiomyocyte injury was at least partially achieved through the activation of the JAK2/STAT3 signaling pathway. CONCLUSION: Hyp can significantly improve cardiac function, ameliorate myocardial hypertrophy and myocardial remodeling in MI mice. The mechanism may be related to improving mitochondrial autophagy of cardiomyocytes to maintain the advantage of autophagy, and blocking apoptosis pathway through phagocytosis, thus suppressing apoptosis level of cardiomyocytes. These effects of Hyp are achieved, at least in part, by activating the JAK2/STAT3 signaling pathway.

Janus particle-engineered structural lipiodol droplets for arterial embolization.

Embolization (utilizing embolic materials to block blood vessels) has been considered one of the most promising strategies for clinical disease treatments. However, the existing embolic materials have poor embolization effectiveness, posing a great challenge to highly efficient embolization. In this study, we construct Janus particle-engineered structural lipiodol droplets by programming the self-assembly of Janus particles at the lipiodol-water interface. As a result, we achieve highly efficient renal embolization in rabbits. The obtained structural lipiodol droplets exhibit excellent mechanical stability and viscoelasticity, enabling them to closely pack together to efficiently embolize the feeding artery. They also feature good viscoelastic deformation capacities and can travel distally to embolize finer vasculatures down to 40 µm. After 14 days post-embolization, the Janus particle-engineered structural lipiodol droplets achieve efficient embolization without evidence of recanalization or non-target embolization, exhibiting embolization effectiveness superior to the clinical lipiodol-based emulsion. Our strategy provides an alternative approach to large-scale fabricate embolic materials for highly efficient embolization and exhibits good potential for clinical applications.

Edge-enhanced dual discriminator generative adversarial network for fast MRI with parallel imaging using multi-view information.

In clinical medicine, magnetic resonance imaging (MRI) is one of the most important tools for diagnosis, triage, prognosis, and treatment planning. However, MRI suffers from an inherent slow data acquisition process because data is collected sequentially in k-space. In recent years, most MRI reconstruction methods proposed in the literature focus on holistic image reconstruction rather than enhancing the edge information. This work steps aside this general trend by elaborating on the enhancement of edge information. Specifically, we introduce a novel parallel imaging coupled dual discriminator generative adversarial network (PIDD-GAN) for fast multi-channel MRI reconstruction by incorporating multi-view information. The dual discriminator design aims to improve the edge information in MRI reconstruction. One discriminator is used for holistic image reconstruction, whereas the other one is responsible for enhancing edge information. An improved U-Net with local and global residual learning is proposed for the generator. Frequency channel attention blocks (FCA Blocks) are embedded in the generator for incorporating attention mechanisms. Content loss is introduced to train the generator for better reconstruction quality. We performed comprehensive experiments on Calgary-Campinas public brain MR dataset and compared our method with state-of-the-art MRI reconstruction methods. Ablation studies of residual learning were conducted on the MICCAI13 dataset to validate the proposed modules. Results show that our PIDD-GAN provides high-quality reconstructed MR images, with well-preserved edge information. The time of single-image reconstruction is below 5ms, which meets the demand of faster processing.

Achieving visible and near-infrared dual-emitting mechanoluminescence in Mn2+ single-doped magnesium aluminate spinel.

Visible (VIS) and near-infrared (NIR) mechanoluminescence (ML) materials have been developed rapidly for use in energy conversion, biological applications and mechanical sensing. The realization of visible and NIR ML in single host materials meets the dual requirements of visualization and anti-interference for high-precision mechanical sensing. In this work, Mn2+ single-doped magnesium aluminate spinel MgAl2O4 with excellent ML performance was studied in detail. Bright, visible green and NIR ML were achieved under mechanical stimulation, and the ratio between visible and NIR ML intensity can be regulated by manipulating the doping concentration of Mn2+. The generation of ML without additional pre-irradiation proved that the self-powered ML phenomenon was independent of trap. The functional relationship between mechanical parameters and ML intensity indicated that the doped spinel can be used for visualization, anti-interference and non-contact mechanical sensing. In addition, the NIR ML of MgAl2O4:Mn2+, centered at 835 nm, is located in the first NIR window (NIR-I, 650-950 nm), which effectively penetrates living tissue such as skin, fat, and lean meat, respectively, showing that it has potential applications in in vivo optical imaging.

Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation.

Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 (KMT2B) are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) oocytes using ultra-low input ChIP-seq, with comparisons to DNA methylation and gene expression analyses. H3K4me3 was redistributed in Setd1b cKO oocytes showing losses at active gene promoters associated with downregulated gene expression. Remarkably, many regions also gained H3K4me3, in particular those that were DNA hypomethylated, transcriptionally inactive and CpG-rich, which are hallmarks of MLL2 targets. Consequently, loss of SETD1B disrupts the balance between MLL2 and de novo DNA methyltransferases in determining the epigenetic landscape during oogenesis. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to gene expression and MLL2 to CpG content.

Protective Effects of Total Flavonoids from Lysimachia christinae on Calcium Oxalate-Induced Oxidative Stress in a Renal Cell Line and Renal Tissue.

Oxidative stress (OS) in renal tubular epithelial cells (RTECs) is induced by calcium oxalate (CaOx) stones and plays an important role in the pathology of CaOx nephrolithiasis. The nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important endogenous antioxidant pathway. Flavonoids are compounds with 2-phenylchromone as the basic mother nucleus and are natural antioxidant components of Lysimachia christinae. Our previous studies demonstrated that the total flavonoids from L. christinae (TFL) reduced calcium and oxalic acid concentrations in urine, thus inhibiting CaOx stone formation. We also showed that TFL can reduce OS in renal tissue. However, whether TFL inhibit the formation of CaOx stones through the Nrf2/ARE pathway requires further investigation. Here, we found that TFL protected against injury to a renal cell line and renal tissue, reduced CaOx-induced OS in renal tissue, and reduced CaOx crystal formation. In addition, TFL significantly increased nuclear Nrf2 and the expression of the downstream antioxidant genes heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1). Furthermore, TFL increased superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) content, thereby alleviating OS in RTECs. Silencing Nrf2 expression blocked the protective effect of TFL on CaOx-induced OS. Taken together, our findings indicate that TFL reduce CaOx-induced OS in renal tissue by activating the Nrf2/ARE pathway.

Intelligent Bimetallic Nanoagents as Reactive Oxygen Species Initiator System for Effective Combination Phototherapy.

Phototherapy is a promising oncotherapy method. However, there are various factors greatly restricted phototherapy development, including poor tumor-specific accumulation, the hypoxia in solid tumor, and the systemic phototoxicity of photosensitizer. Herein, a tumor microenvironment (TME)-responsive intelligent bimetallic nanoagents (HSA-Pd-Fe-Ce6 NAs) composed of human serum albumin (HSA), palladium-iron (Pd-Fe) bimetallic particles, and chlorin e6 (Ce6) was designed for effective combination phototherapy. The Pd-Fe part in the HSA-Pd-Fe-Ce6 NAs would react with the endogenous hydrogen peroxide (H2O2) in an acidic ambiance within tumor to generate cytotoxic superoxide anion free radical through the "Fenton-like reaction." H2O2, coupled with highly toxic singlet oxygen (1O2) caused by the Ce6 component under the irradiation of 660 nm laser, resulted in synergistic cancer therapy effects in hypoxia surroundings. Besides, this nanoagents could result in hyperpyrexia-induced cell apoptosis because of superior absorption performance in near-infrared wavelength window bringing about excellent photothermal conversion efficiency. The cell cytotoxicity results showed that the survival rate after treated by 40 µg mL-1 nanoagents was only 17%, which reveals that the HSA-Pd-Fe-Ce6 NAs had the advantage of efficient and controllable phototherapy. In short, it exhibited excellent hypoxia-resistant combination phototherapy efficacy in vitro. Therefore, the multifunctional nanoagents are powerful and provide a new avenue for effective combination phototherapy.

Monitoring and evaluating the quality consistency of Compound Bismuth Aluminate tablets by a simple quantified ratio fingerprint method combined with simultaneous determination of five compounds and correlated with antioxidant activities.

A combination method of multi-wavelength fingerprinting and multi-component quantification by high performance liquid chromatography (HPLC) coupled with diode array detector (DAD) was developed and validated to monitor and evaluate the quality consistency of herbal medicines (HM) in the classical preparation Compound Bismuth Aluminate tablets (CBAT). The validation results demonstrated that our method met the requirements of fingerprint analysis and quantification analysis with suitable linearity, precision, accuracy, limits of detection (LOD) and limits of quantification (LOQ). In the fingerprint assessments, rather than using conventional qualitative "Similarity" as a criterion, the simple quantified ratio fingerprint method (SQRFM) was recommended, which has an important quantified fingerprint advantage over the "Similarity" approach. SQRFM qualitatively and quantitatively offers the scientific criteria for traditional Chinese medicines (TCM)/HM quality pyramid and warning gate in terms of three parameters. In order to combine the comprehensive characterization of multi-wavelength fingerprints, an integrated fingerprint assessment strategy based on information entropy was set up involving a super-information characteristic digitized parameter of fingerprints, which reveals the total entropy value and absolute information amount about the fingerprints and, thus, offers an excellent method for fingerprint integration. The correlation results between quantified fingerprints and quantitative determination of 5 marker compounds, including glycyrrhizic acid (GLY), liquiritin (LQ), isoliquiritigenin (ILG), isoliquiritin (ILQ) and isoliquiritin apioside (ILA), indicated that multi-component quantification could be replaced by quantified fingerprints. The Fenton reaction was employed to determine the antioxidant activities of CBAT samples in vitro, and they were correlated with HPLC fingerprint components using the partial least squares regression (PLSR) method. In summary, the method of multi-wavelength fingerprints combined with antioxidant activities has been proved to be a feasible and scientific procedure for monitoring and evaluating the quality consistency of CBAT.