Conduction system pacing improves the outcomes on patients with high percentage of ventricular pacing and heart failure with mildly reduced ejection fraction.

Aims: This study aimed to investigate the efficacy and safety of CSP in patients with a high percentage of ventricular pacing and heart failure with HFmrEF. Methods: Patients who underwent CSP for HFmrEF and ventricular pacing >40% were consecutively enrolled from January 2018 to May 2021. All participants were followed up at least 12 months. Clinical data including cardiac performance and lead outcomes were compared before and after the procedure. Left ventricular ejection fraction (LVEF) was measured using the biplane Simpson's method. HFmrEF was defined as heart failure with the LVEF ranging from 41%-49%. Results: CSP was successfully performed in 64 cases (96.97%), which included 16 cases of left bundle branch pacing (LBBP) and 48 cases of His bundle pacing (HBP). After a mean of 23.12 ± 8.17 months follow-up, NYHA classification (P < 0.001), LVEF (42.45 ± 1.84% vs. 49.97 ± 3.57%, P < 0.001) and left ventricular end diastolic diameter (LVEDD) (55.59 ± 6.17 mm vs. 51.66 ± 3.48 mm, P < 0.001) improved significantly. During follow-up, more than half (39/64,60.9%) of patients returned to normal LVEF and LVEDD with complete reverse remodeling. The pacing threshold in LBBP was lower (0.90 ± 0.27 V@0.4 ms vs. 1.61 ± 0.71 V@0.4 ms, P < 0.001) than that in HBP. No perforation, electrode dislodging, thrombosis or infection was observed during follow-up. Conclusions: CSP could improve the clinical outcomes in patients with HFmrEF and a high percentage of ventricular pacing. LBBP might be a better choice because of its feasibility and safety, especially in patients with infranodal atrioventricular block.

Metabolome and transcriptome analysis of eleutheroside B biosynthesis pathway in Eleutherococcus senticosus.

Eleutheroside B (syringin) is a medicinal active ingredient extracted from Eleutherococcus senticosus (Ruper. et Maxim.) Maxim with high clinical application value. However, its synthesis pathway remains unknown. Here, we analyzed the eleutheroside B biosynthesis pathway in E. senticosus. Consequently, metabolomic and transcriptomic analyses identified 461 differentially expressed genes (DEGs) and 425 metabolites. Further, we identified 7 DEGs and 67 metabolites involved in the eleutheroside B biosynthetic pathway in the eleutheroside B high and low plants. The correlation between the gene and metabolites was explored using the pearson correlation coefficient (PCC) analysis. Caffeoyl-CoA O-methyltransferase, caffeic acid-O-methyltransferase, ß-amyrin synthase (ß-AS) genes, NAC5, and HB5 transcription factors were identified as candidate genes and transcription factors related to the eleutheroside B synthesis. Eleutheroside B content was the highest at the young stage of the leaves both in the high and low eleutheroside B plants. Quantitative real-time polymerase chain reaction revealed that phenylalanine ammonia-lyase1, cinnamate 4-hydroxylase, ß-AS, and leucoanthocyanidin reductase gene had higher expression levels at the young stage of the leaves in the low eleutheroside B plants but lower expression levels in the high eleutheroside B plants. In the present study, we complemented the eleutheroside B biosynthetic pathway by analyzing the expression levels of relevant genes and metabolite accumulation patterns.

Adaptive Evolution of Chalcone Isomerase Superfamily in Fagaceae.

Chalcone Isomerase (CHI) catalyzes the biosynthesis of flavonoids and secondary metabolism in plants. Currently, there is no systematic analysis of CHIs gene family in Fagaceae which is available. In this study, twenty-two CHI proteins were identified in five species of the Fagaceae family. The CHI superfamily in Fagaceae can be classified into three subfamilies and five groups using phylogenetic analysis, analysis of physicochemical properties, and structural prediction. Results indicated that serine (Ser) and isoleucine (Ile) residues determine the substrate preferred by active Type I Fagaceae CHI, and the chalcone isomerase-like (CHIL) of Fagaceae had active site residues. Adaptive analysis of CHIs showed that CHIs are subject to selection pressure. The active CHI gene of Fagaceae was located in the cytoplasm, and it had the typical gene structure of CHI and contains four exons. All the twenty-two identified CHIs had the conserved domain motif 3, and the different groups had their own structural characteristics. In the process of fatty acid binding protein (FAP) evolution to CHIL and CHI, the physical and chemical properties of proteins also had significant differences in addition to changes in protein functions.

Recent developments in Hericium erinaceus polysaccharides: extraction, purification, structural characteristics and biological activities.

Hericium erinaceus (H. erinaceus), an edible mushroom with medicinal value, has a long history of usage in China and other oriental countries. Polysaccharide is supposed to be one of the major bioactive compounds in H. erinaceus, which possesses immunomodulating, anti-cancer, antioxidant, gastroprotection and intestinal health promotion, neuroprotective, hepatoprotective, antihpyerglycemic and hypolipidemic activities. In this review, the current advancements on extraction, purification, structural characteristics and biological activities of polysaccharide from different sources (fruiting body, mycelium and culture broth) of H. erinaceus were summarized. Among these aspects, summaries of the structural characteristics focused on the purified polysaccharides. Meanwhile, comparisons on the structural characteristics among the purified polysaccharides obtained from above three sources were made. Moreover, their biological activities were introduced on the basis of in vivo and in vitro experiments, and some possible action mechanisms were listed. Furthermore, the structure-activity relationship of the polysaccharide was discussed. New perspectives for the future work of Hericium erinaceus polysaccharide were also proposed. HIGHLIGHTS Extraction, purification, structural characteristics and biological activities of Hericium erinaceus polysaccharide (HEP) were summarized. Structural characteristics of the purified polysaccharides from different sources (fruiting body, mycelium and culture broth) of Hericium erinaceus were summarized and compared. Structure-activity relationship of HEP was discussed, and new perspectives for the future work of this polysaccharide were proposed.

lncRNA AFAP1-AS1 Promotes Migration and Invasion of Non-Small Cell Lung Cancer via Up-Regulating IRF7 and the RIG-I-Like Receptor Signaling Pathway.

BACKGROUND/AIMS: Accumulating evidence has highlighted the importance of long non-coding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in tumor biology. Among others, actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been associated with non-small cell lung cancer (NSCLC). However, it remains unclear how AFAP1-AS1 participates in the development and progression of NSCLC. METHODS: The peripheral blood samples were collected from patients with NSCLC. White blood cell subsets were classified and levels of interleukin (IL)-10, IL-12 and IFN-γ in serum were measured. We then identified its target gene of AFAP1-AS1 via bioinformatics methods. NSCLC cell line with the highest expression of AFAP1-AS1, i.e. H1975 was selected for in vitro experiments. A series of inhibitor, vector and siRNA were employed to validate the regulatory mechanisms of AFAP1-AS1 in the development and progression of NSCLC. Cell proliferation was detected by MTT assay and EdU staining. Cell migration and invasion, and cell cycle and apoptosis were measured by transwell assay and flow cytometry, respectively. RESULTS: A high expression of AFAP1-AS1 was identified in NSCLC, alongside with a reduced level of IL-12 and increased levels of IL-10 and interferon (IFN)-γ. Aberrant expressions of AFAP1-AS1 were associated with pathological grade, TNM staging and metastatic potential of NSCLC. AFAP1-AS1 could activate interferon regulatory factor (IRF)7, the retinoid-inducible protein (RIG)-I-like receptor signaling pathway and Bcl-2 in vitro. Over-expression of AFAP1-AS1 promoted NSCLC cell proliferation, invasion and migration while inhibiting cell apoptosis. CONCLUSION: lncRNA AFAP1-AS1 promotes migration and invasion of non-small cell lung cancer via up-regulating IRF7 and the RIG-I-like receptor signaling pathway.

Pharmacologic Interventions in Preventing Ovarian Hyperstimulation Syndrome: A Systematic Review and Network Meta-Analysis.

Ovarian hyperstimulation syndrome (OHSS) is a severe iatrogenic complication of controlled ovarian stimulation. Randomised controlled trials (RCTs) have proven several pharmacologic interventions to be effective in OHSS prevention, but these trials have seldom compared multiple drugs. We identified randomised controlled trials (RCTs) through June 2015 by searching databases and compared 11 intervention strategies in preventing OHSS (primary outcome) and their influence on pregnancy rate (secondary outcome). A network meta-analysis was used to evaluate the relative effectiveness among treatments and to create a rank probability table. Thirty-one RCTs were identified, including 7181 participants. Five pharmacologic interventions were superior to placebo in decreasing OHSS incidence: aspirin [relative risk (RR) 0.07, 95% credible interval (CrI) 0.01-0.30, p < 0.05], intravenous (IV) calcium [RR 0.11, 95% CrI 0.02-0.54, p < 0.05], cabergoline [RR 0.17, 95% CrI 0.06-0.43, p < 0.05], metformin [RR 0.20, 95% CrI 0.07-0.59, p < 0.05] and IV hydroxyethyl starch (HES) [RR 0.26, 95% CrI 0.05-0.99, p < 0.05]. The rank probability demonstrated aspirin (Rank 1: 36%) and IV calcium (Rank 1: 35%) to be the most efficacious. Additionally, albumin might decrease the pregnancy rate when compared with placebo [RR 0.85, 95% CI 0.74-0.97, p < 0.05]. This conclusion provides a relative standard and objective reference for choosing an OHSS prophylactic agent.

[Quality comparison andstructural characteristics of material basic composition of Danshen injection from different manufacturers].

HPLC was used to analyze the chromatographic fingerprints and determine the contents of tanshinol, protocatechuic acid, protocatechuic aldehyde, caffeic acid, isoferulic acid, lithospermic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A, and salvianolic acid C in Danshen injection from 10 different manufacturers. The significant differences of phenolic compounds in Danshen injection from ten manufacturers were investigated by using F test. The results showed that the similarity degree of Danshen injection from ten manufacturers was above 0.9 and there was significant difference in mass fraction of phenolic compounds between the samples from different manufacturers. The analysis of mass fraction of effective phenolic components and their structural ratios in Danshen injection from the different manufacturers showed significant differences, indicating that the Danshen injection available in market had different curative effects and with significant differences in structural ratios.

Nicorandil inhibits oxidative stress and amyloid-ß precursor protein processing in SH-SY5Y cells overexpressing APPsw.

It has been demonstrated that ATP-sensitive potassium (KATP) channel activation has neuroprotective effects against neuronal damage induced by hypoxia, ischemia or metabolism stress. This study investigated the multiply protective effects of KATP channel opener nicorandil against neurotoxicity in SH-SY5Y cells transiently transfected with Swedish mutant APP (APPsw) and also the potential involvement of PI3K/Akt/GSK-3ß pathway. Cells were treated with nicorandil (1 mM) for 24 h with and without glibenclamide (10 µM), a KATP channel inhibitor. Then the cells were collected for Hoechst33342, biochemical assays, real-time PCR, western blot and ELISA assay. Our results showed that nicorandil reduced apoptosis and decreased oxidative stress. Moreover, nicorandil down regulated APP695 mRNA and APP695 protein expression, also reduced Aß1-42 levels in the medium. In addition, nicorandil increased the protein levels of p-Akt and p-GSK-3ß by PI3K activation. Applying a PI3K inhibitor, LY294002 blocked the protection. These findings suggest nicorandil to be a potential therapeutic agent to treat Alzheimer's disease (AD).

Cbl-b and PI3K/Akt pathway are differently involved in oxygen-glucose deprivation preconditioning in PC12 cells.

BACKGROUND: Transient sublethal ischemia is known as ischemic preconditioning, which enables cells and tissues to survive subsequent prolonged lethal ischemic injury. Ischemic preconditioning exerts neuroprotection through phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Cbl-b belongs to the Casitas B-lineage lymphoma (Cbl) family, and it can regulate the cell signal transduction.The roles of ubiquitin ligase Cbl-b and PI3K/Akt pathway and the relationship between them in oxygen-glucose deprivation preconditioning (OGDPC) in PC12 cells were investigated in the present study. METHODS: Oxygen and glucose deprivation (OGD) model in PC12 cells was used in the present study. The 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, nuclear staining with Hoechst 33258, and Western blotting were applied to explore the roles of Cbl-b and PI3K/Akt pathway and the relationship between them in OGDPC in PC12 cells. RESULTS: Cell viability was significantly changed by OGD and OGDPC. OGD significantly decreased cell viability compared with the control group (P < 0.05), and preconditioning could rescue this damage was demonstrated by the increase of cell viability (P < 0.05). The expression of Cbl-b was significantly increased after OGD treatment. However, the activation of Akt and GSK3ß was greatly inhibited. Preconditioning could inhibit the increase of Cbl-b caused by OGD and increase the activation of Akt and GSK3ß. LY294002, a specific inhibitor of PI3K, could effectively inhibit the increase of Akt and GSK3ß after preconditioning treatment. It partly inhibited the decrease of Cbl-b expression after preconditioning treatment. CONCLUSION: Ubiquitin ligase Cbl-b and PI3K/Akt pathway are differently involved in OGDPC in PC12 cells.

[ShRNA-mediated silencing of MDM2 inhibits growth of HepG2 hepatocellular carcinoma cells xenografted in nude mice].

OBJECTIVE: To construct a short hairpin (sh)RNA targeting the gene encoding the MDM2 oncoprotein in order to investigate its role in human hepatocellular carcinoma (HCC) and its potential for use as a gene therapy strategy to inhibit HCC growth in vivo. METHODS: Small interfering (si)RNAs were designed targeting the MDM2 gene (siMDM2-1 and siMDM2-2) and unrelated sequences (negative control) and cloned into the expression plasmid pGCSilencer-U6-neo-GFP. A HCC mouse model was established by subcutaneous inoculation of HepG2 cells (2 x 10(6) in 0.2 ml) into 20 nude mice. The inoculated mice were divided into four equal groups for tumor-localized injections of saline, negative control siRNA plasmid, siMDM2-1 plasmid, and siMDM2-2 plasmid. Tumor growth was observed daily (by caliper measurement) for one month, when mice were sacrificed by cervical dislocation. The tumor mass was resected for analysis of tumor inhibition rate (% = [(average tumor weight of control group - average tumor weight of treatment group) / average tumor weight of control group x 100]) and effects on MDM2 and p53 mRNA and protein expression (by reverse transcription- PCR and western blotting, both normalized to beta-actin). Significance of between-group differences was assessed by one-way ANOVA or LSD test; pairwise comparisons were made by the Chi-squared test. RESULTS: siMDM2-1 and siMDM2-2 suppressed the xenografted tumor growth remarkably (60.6% and 54.6% inhibition rates, respectively), significantly reduced the expression ofMDM2 gene (62.8% and 61.6%) and protein (60.7% and 59.5%), and significantly increased p53 gene (47.1% and 45.6%) and protein (45.9% and 44.3%) (all, P < 0.05). CONCLUSION: shRNA-mediated silencing of the MDM2 gene effectively inhibits HCC tumorigenesis of subcutaneously xenografted HepG2 cells in nude mice, and the mechanism may involve p53.

[The study on protective effect of sphingosine-1-phosphate in cardiomyocytes].

OBJECTIVE: To explore the mechanism of protective effect of Sphingosine-1-phosphate(S1P) in cultured neonatal rat cardiomyocytes dining simulated hypoxia/reoxygenation. METHODS: On the basis of culturing neonatal rat cardiomyocytes, the model of hypoxia-reoxygennation was built by using method of Liquid Paraffin covering, the impact of S1P on apoptosis and p-Akt and mitochondrial membrane potential were studied by using method of Propidine Iodide staining and Western blot and Bhodanmine123 staining. RESULTS: SiP could reduce apoptosis rate (P < 0.01) and stabilize the mitochondrial membrane potential (P < 0.05) and improved the level of p-Akt1 (P < 0.01) in hypoxia/reoxygenation cardiomyocytes significantly. But wonnannin could block these effects of S1P partially. CONCLUSION: SiP can obviously restrain apoptosis in curtured rat neonatal cardiomyocytes during simulated hypoxia/reoxygenation. Stabilization of mitochondrial membrane potential by P13K-AM signaling pathway is likely to play a role in protective action of S1P.

[Therapeutic effects of small interfering RNA targeting MDM2 on human osteosarcoma cells].

OBJECTIVE: To investigate the inhibitory effect of the small interfering RNA targeting mdm2 gene on the growth of osteosarcoma cells. METHODS: PGCsilencerTM-mdm2 siRNA was constructed and transfected into the osteosarcoma cell line U2OS cells. The inhibitory effects on mdm2 were determined by RT-PCR and Western blot analysis. The cell growth activity was determined by MTT assay, and the cell apoptosis was examined by flow cytometry. The therapeutic effects of simdm2 was assessed on the nude mouse model of transplanted tumor. RESULTS: The simdm2 plasmid was successfully constructed. After simdm2 being transfected into the U2OS cells, the expressions of mdm2 gene and protein were significantly inhibited. The ability of cell growth activity decreased greatly and cell apoptosis occurred apparently. There was no significant difference between the negative control group and non-transfected group. The growth of xenograft tumor in simdm2 transfected nude mice was inhibited and the expressions of mdm2 gene and protein were down-regulated remarkably. CONCLUSION: siRNA targeting mdm2 gene inhibits the mdm2 expression in osteosarcoma U2OS cells and the growth of osteosarcoma in nude mice.