Effects of fermented feed on growth performance, serum biochemical indexes, antioxidant capacity, and intestinal health of lion-head goslings.

Introduction: The aim of this study was to evaluate the effects of fermented feed on growth performance, antioxidant indexes and intestinal health in lion-head goslings. Methods: 288 male lion-head goslings (one-day-old) were randomly divided into four groups (6 replicates per group, 12 samples per replicate): control group (basal diet) and fermented feed (FF) groups (basal diet supplemented with 2.5, 5.0 and 7.5% FF, respectively). The experimental period lasted 28 days. Results: The results showed that 5.0 and 7.5% FF groups decreased feed conversion rate (FCR) when compared with the control group (p < 0.05). The 5.0% FF group reduced the activity of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in serum; while the 7.5% FF group decreased the concentration of total cholesterol (TC), ALP and LDH activity (p < 0.05). Furthermore, the 7.5% FF group significantly increased total antioxidant capacity (T-AOC) in serum (p < 0.05); 2.5% and 5.0% FF groups significantly increased glutathione peroxidase (GSH-Px) in serum (p < 0.05); all FF groups increased the activity of superoxide dismutase (T-SOD) in serum (p < 0.05). For intestinal health, the villous height and villi/crypt ratio in jejunum were increased in all FF groups, but crypt depth was decreased (p < 0.05); The 5.0% FF groups enhanced T-AOC activity in jejunum (p < 0.05); The 2.5% and 5.0% FF groups enhanced GSH-Px activity (p < 0.05) in jejunum; All FF groups reduced malondialdehyde (MDA) level in jejunum (p < 0.05). LEfSe analysis showed that the cecum microbiota was significantly dominant in the 2.5% FF group compared to the control group including Firmicutes, Lactobacillales, Lactobacillus, and Prevotella; the flora that were significantly dominant in the 5.0% FF group compared to the control group included Bacteroidaceae, Bacteroides, Megamonas, and Prevotella; and the groups that were significantly dominant in the 7.5% FF group compared to the control group included Bacteroidota, Bacteroides, Bacteroidaceae, and Ruminococcaceae. Discussion: In summary, dietary FF supplementation improved growth performance, serum biochemical parameters and antioxidant capacity of lion-head goslings, as well as improved jejunal tissue morphology and optimized intestinal flora structure. In particular, the FF addition at a dose of 7.5% was relatively more effective for lion- head goslings.

Genetic diversity, population structure, and DNA fingerprinting of Ailanthus altissima var. erythrocarpa based on EST-SSR markers.

Ailanthus altissima var. erythrocarpa is an A. altissima variety with high economic, ecological and ornamental value, but there have been no reports on the development of SSR primers for it. According to the SSR primer information provided by the transcriptome of A. altissima var. erythrocarpa, 120 individuals with different redness levels were used to screen polymorphic primers. Transcriptomic analysis revealed 10,681 SSR loci, of which mononucleotide repeats were dominant (58.3%), followed by dinucleotide and trinucleotide repeats (16.6%, 15.1%) and pentanucleotide repeats (0.2%). Among 140 pairs of randomly selected primers, nineteen pairs of core primers with high polymorphism were obtained. The average number of alleles (Na), average number of effective alleles (Ne), average Shannon's diversity index (I), average observed heterozygosity (Ho), average expected heterozygosity (He), fixation index (F) and polymorphic information content (PIC) were 11.623, 4.098, 1.626, 0.516, 0.696, 0.232 and 0.671, respectively. Nineteen EST-SSR markers were used to study the genetic diversity and population structure of A. altissima var. erythrocarpa. The phylogenetic tree, PCoA, and structure analysis all divided the tested resources into two categories, clearly showing the genetic variation between individuals. The population showed high genetic diversity, mainly derived from intraspecific variation. Among nineteen pairs of primers, 4 pairs (p33, p15, p46, p92) could effectively distinguish and be used for fingerprinting of the tested materials. This study is of great significance for genetic diversity analysis and molecular-assisted breeding of A. altissima var. erythrocarpa.

Intra-articular Injection of Baicalein Inhibits Cartilage Catabolism and NLRP3 Inflammasome Signaling in a Posttraumatic OA Model.

Baicalein has been shown to have chondroprotective potential in vitro. However, its effect on disease modification in osteoarthritis (OA) is largely unknown. The present study is aimed at determining whether baicalein could slow the progression of OA and inhibit OA-related inflammation in a rat model of destabilization of the medial meniscus (DMM) and the underlying mechanisms. The rats subjected to DMM surgery were treated with baicalein (0.8, 1.6, and 3.2 µg/L, 50 µL, once a week) by intra-articular injection for 6 weeks. Dexamethasone (0.4 mg/mL, 50 µL, once a week) was used as a positive control. Histologic grading of cartilage degeneration was performed using the Osteoarthritis Research Society International (OARSI) recommended grading system (on a scale of 0-6). The expression levels of molecules associated with cartilage homeostasis and inflammatory cytokines were analyzed; moreover, the NLRP3 inflammasome activation and cartilage oxidative stress-associated molecules were determined. Baicalein treatment reduced the OARSI score and slowed OA disease progression in a dose-dependent manner within a certain range. Compared with DMM rats, intra-articular injection of baicalein led to (1) reduced levels of inflammatory mediates such as IL-1ß and TNF-α, (2) reduced immunochemical staining of MMP-13 and ADAMTS-5, (3) suppressed immunochemical staining loss of type II collagen, (4) reduced expression of cartilage degradation markers including CTX-II and COMP in urine, and (5) inhibited NLRP3 inflammasome activation rather than regulated expression of SOD, GSH, and MDA. In contrast to the administration of baicalein, dexamethasone injection showed similar effects to slow OA progression, while dexamethasone inhibited NLRP3 inflammasome partly through decreasing levels of SOD, GSH, and MDA. This study indicated that baicalein may have the potential for OA prevention and exerts anti-inflammatory effects partly via suppressing NLRP3 inflammasome activation without affecting oxidative stress-associated molecules, and inhibition of cartilage catabolism enzymes in an OA rat model.

Translation, ribosome biogenesis, and oxidative damage caused by chlorpyrifos exposure to common carp (Cyprinus carpio L.) liver: application of combined RNA-seq with sRNA-seq in risk evaluation of environmental toxicant chlorpyrifos.

Pesticide chlorpyrifos (CPF) is a widespread environmental pollutant gaining attention as it is highly injurious to aquatic life. Although the toxicity of CPF is well characterized, but the mechanism of toxic response especially, the hepatotoxicity remained unclear. In this study, we performed integrated analysis, including micro-RNA (miRNA) and small RNA (sRNA) to analyze CPF exposure responding genes and enrichment pathways. A total of 23,742 expressed genes were detected and out of these expression levels of 1746 were changed significantly. Majority of them participated in protein biosynthesis, nucleotide binding, and oxidation-reduction activities. In extensive analysis of micro-RNA (miRNA) expression profiles by comparing CPF treated carp with control, we identified 214 novel miRNAs with CPM > 5 in at least one sample. The miRNAs have the same change in direction compared with overlapped mRNA pairs in upregulated genes, suggesting potential positive correlation. As a whole, we detected many differently expressed genes (DEGs) and miRNAs, which may be used as the biomarkers for the detection of CPF pollution in water and aquatic product safety. However, their functions are required to be deeply analyzed, especially more samples or time pointed data are needed to illustrate their concrete mechanism.

Galectin-1 Inhibited LPS-Induced Autophagy and Apoptosis of Human Periodontal Ligament Stem Cells.

Periodontitis is a widespread human chronic inflammatory disease of the tooth-surrounding tissues, which induces the destruction of periodontium and pathologic loss of teeth among adults. It has been reported that interleukin (IL)-17 was significantly increased in periodontitis patients compared to controls, while galectin-1 (Gal-1) was lower. Interestingly, it is found that Gal-1 treatment reduced systemic IL-17 levels. Hence, the aim of the present study was to explore the effect of Gal-1 on periodontitis development and investigate its underlying mechanism. In this study, Gal-1 was poorly expressed in lipopolysaccharide (LPS)-induced human periodontal ligament stem cells (hPDLSCs), and Gal-1 overexpression attenuated the production of inflammatory cytokines induced by LPS. Moreover, Gal-1 overexpression alleviated LPS-induced cell autophagy and apoptosis and reduced the expressions of IL-17A and IL-17R. Interestingly, IL-17A reversed the effect of Gal-1 on cell autophagy, inflammation, and cell apoptosis induced by the LPS challenge. In conclusion, Gal-1 inhibited LPS-induced autophagy and apoptosis of hPDLSC via regulation of IL-17A expression. Therefore, Gal-1 may have promising potential in regenerating periodontium.

Impact of statin on long-term outcome among patients with end-stage renal disease with acute myocardial infarction (AMI): a nationwide case-control study.

BACKGROUND: Use of statin has been associated with reduced risk of cardiovascular diseases events and mortality. However, in patients with end-stage renal disease (ESRD), the protective effects of statin are controversial. To evaluate the impact of chronic statin use on clinical outcomes of patients with acute myocardial infarction (AMI) with ESRD. METHODS: We enrolled 8056 patients with ESRD who were initially diagnosed and admitted for first AMI from Taiwan's National Health Insurance Research Database. Of which, 2134 patients underwent statin therapy. We randomly selected and use age, sex, hypertension, diabetes mellitus (DM), peripheral vascular diseases (PVD), heart failure (HF), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease, matched with the study group as controls (non-stain user). We compared the effects of statin use in term of all-cause death among patients with AMI with ESRD. RESULTS: Statin use resulted in a significantly higher survival rate in patients ith AMI with ESRD compared with non-statin users. After adjusted the comorbidities the male patients and patients with DM, PVD, HF and CVA had lower long-term survival rate (all p<0.001). Patients who underwent percutaneous coronary intervention (p<0.001), ACE inhibitors/angiotensin II receptor blockers (p<0.001), ß receptor blockers (p<0.001) and statin therapy (p=0.007) had better long-term survival rate. Patients with AMI with ESRD on statin therapy exhibited a significantly lower risk of mortality compared with non-statin users (p<0.0001). CONCLUSION: Among patients with ESRD with AMI, statin therapy was associated with reduced all-cause mortality.

Effect of Surface Ultrasonic Rolling Treatment on Rolling Contact Fatigue Life of D2 Wheel Steel.

A GPM-30 fatigue machine was used to investigate the influence of surface ultrasonic rolling (SURT) on the rolling contact fatigue (RCF) life of D2 wheel steel. The experimental results present that the RCF life of the grinding processing sample is 4.1 × 105 cycles. During the RCF process, the flaking of the fine grain layer and high surface roughness of the grinding processing sample cause the production of RCF cracks. When the samples are treated by SURT with 0.2 MPa and 0.4 MPa, the RCF life is 9.2 × 105 cycles and 9.6 × 105 cycles, respectively. After SURT, the surface roughness of the samples is reduced, and a certain thickness of gradient-plastic-deformation layer and a residual-compressive-stress layer are produced. These factors lead to the improvement of the RCF property. However, when the static pressure increases to 0.6 MPa during SURT, the RCF life of the sample is reduced during RCF testing. The micro-cracks, which are formed during SURT, become the crack source and cause the formation of RCF cracks, decreasing of the RCF life.

L-Theanine Reduced the Development of Knee Osteoarthritis in Rats via Its Anti-Inflammation and Anti-Matrix Degradation Actions: In Vivo and In Vitro Study.

The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)ß-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1ß (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1ß-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1ß-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.

Safety and Cumulative Incidence of Major Cardiovascular Events with Ticagrelor in Taiwanese Patients with Non-ST-Segment Elevation Myocardial Infarction: A 12-Month, Prospective, Phase IV, Multicenter, Single-Arm Study.

BACKGROUND: Ticagrelor, an oral, direct-acting, and reversible P2Y12 receptor antagonist, inhibits platelet activation and aggregation. This phase IV, single-arm study analyzed the safety and tolerability of ticagrelor in Taiwanese patients with non-ST-segment elevation myocardial infarction (NSTEMI) during 1 year of follow-up. METHODS: Patients aged ≥ 20 years with an index event of NSTEMI received ticagrelor (180 mg loading and 90 mg doses twice daily thereafter) plus low-dose aspirin (100 mg/day) for up to 1 year. Safety was evaluated according to adverse events (AEs), serious AEs (SAEs), and PLATO-defined bleeding events. The cumulative incidence of major cardiovascular (CV) events including CV death, myocardial infarction, and stroke was also evaluated. RESULTS: The safety population included 108 patients across 13 centers in Taiwan. During treatment, 32 (29.6%) patients had ≥ one PLATO-defined bleeding event. Major bleeding events occurred in seven (6.5%) patients with a Kaplan-Meier (KM) estimated event risk [95% confidence interval (CI)] of 7.1% (3.4%-14.4%), including life-threatening bleeding [four (3.7%) patients] and other major bleeding [three (2.8%) patients]. No PLATO-defined fatal bleeding was observed. SAEs were reported in 23 (21.3%) patients. Six (5.6%) patients experienced major CV events during the 1-year follow-up period, with a KM-estimated event risk (95% CI) of 5.6% (2.6%-12.0%). CONCLUSIONS: Ticagrelor for up to 1 year was associated with a low rate of major bleeding events and a low incidence of major CV events in Taiwanese patients with NSTEMI. The overall safety of ticagrelor was in accordance with the known safety profile of ticagrelor.

Influence of Contact Stress on Surface Microstructure and Wear Property of D2/U71Mn Wheel-Rail Material.

To investigate the relationship between surface microstructure and wear mechanism in D2/U71Mn wheel-rail material under different contact stress conditions, rolling wear tests using a GPM-40 wear machine to simulate the wheel-rail operation was performed. After wear tests, an optical microscope (OM), scanning electron microscope (SEM) and micro-hardness testers were used to characterize the microstructure and fatigue wear cracks. The results show that the thickness of the plastic deformation layer and surface hardness is increased with the increase of contact stress. Under high contact stress condition (1200 MPa), the severe plastic deformation layer led to the formation of fatigue wear of wheel-rail samples. Under a contact stress of 700 MPa, the wear mechanism of samples is adhesive wear and wear rate is low. With the increase of contact stress, the fatigue cracks are gradually severe. Under a contact stress of 1200 MPa, the wear mechanism of samples becomes fatigue wear and the fatigue wear cracks cause the increase of wear rate. The fatigue wear can accelerate the wear failure of wheel-rail samples. The fatigue wear cracks of wheel samples are severer than that of rail samples due to both the rate of plastic strain and the content of proeutectoid ferrite.

Down-regulation of long non-coding RNA MEG3 suppresses osteogenic differentiation of periodontal ligament stem cells (PDLSCs) through miR-27a-3p/IGF1 axis in periodontitis.

OBJECTIVE: This study aimed to investigate the roles of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in periodontitis. METHODS: Differentially expressed lncRNAs and mRNAs between periodontitis periodontal ligament tissues and healthy periodontal ligament tissues were selected out using R project. PDLSCs were identified using flow cytometry. Western blot was employed to detect pathway relative proteins. Besides, targeted relationships between lncRNA and miRNA, as well as miRNA and mRNA were verified by dual luciferase reporter gene assay. Osteogenic differentiation of PDLSCs was assessed by alkaline phosphatase (ALP) staining and Alizarin Red Staining (ARS). Markers for osteoblast (Runx2, Osterix, Osteocalcin, Colla1) were detected using western blot. RESULTS: LncRNA MEG3 and IGF1 were both down-regulated, while miR-27a-3p was up-regulated in periodontitis samples compared with healthy samples. Overexpression of MEG3 promoted osteogenic differentiation by enhancing expression of IGF1 yet suppressing expression of miRNA-27a-3p. Meanwhile, the results of ALP and ARS staining indicated that up-regulation of lncRNA MEG3 or IGF1 promoted osteogenic differentiation in PDLSCs, which could be reversed with up-regulation of miRNA-27a-3p. CONCLUSION: Down-regulation of MEG3 suppressed osteogenic differentiation of PDLSCs through miR-27a-3p/IGF1 axis in periodontitis.

Heat shock protein 70 protects the quail cecum against oxidant stress, inflammatory injury, and microbiota imbalance induced by cold stress.

The intent of this study was to investigate the effects of cold stress on oxidative indexes, inflammatory factors, and microbiota in the quail cecum. A total of 192 male quails (15-day-old) were randomly divided into 12 groups (16 in each group) and were exposed to acute (up to 12 h) and chronic (up to 20 D) cold stress at 12 ± 1°C. After cold stress treatment, we examined morphological damage, oxidative stress indexes, inflammatory factors, and intestinal microbiota. Results of morphological examination showed that both acute and chronic cold stress can lead to cecal tissue injury. In addition, both acute and chronic cold stress, especially chronic cold stress can influence the activity of oxidative stress mediators. Glutathione (GSH) and glutathione peroxidase (GSH-Px) activities decreased significantly (p < 0.05), while the nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity increased significantly (p < 0.05). Moreover, mRNA levels of inflammatory factors cyclooxygenase-2 (COX-2), prostaglandin E synthase (PTGES), and heat shock protein 70 (Hsp70) were higher in both acute and chronic cold stress groups when compared with the control group (p < 0.05). Furthermore, the intestinal microbiota was changed in both the acute and chronic cold stress groups. These results suggested that cold stress caused oxidative stress and inflammatory injury in cecal tissues, influenced cecal microbiota, and increased expression of Hsp70, which may contribute in protecting the cecum against cold stress in quails.

Nanosilver/poly (dl-lactic-co-glycolic acid) on titanium implant surfaces for the enhancement of antibacterial properties and osteoinductivity.

Background: Despite titanium (Ti) implants have been commonly used in the medical device field due to their superior biocompatibility, implant-associated bacterial infection remains a major clinical complication. Nanosilver, an effective antibacterial agent against a wide spectrum of bacterial strains, with a low-resistance potential, has attracted much interest too. Incorporation of nanosilver on Ti implants may be a promising approach to prevent biofilm formation. Purpose: The objective of the study was to investigate the antibacterial effects and osteoinductive properties of nanosilver/poly (dl-lactic-co-glycolic acid)-coated titanium (NSPTi). Methods: Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative opportunistic pathogen Pseudomonas aeruginosa (PAO-1) were used to evaluate the antibacterial activity of NSPTi implants through the analysis of bacterial colonization in vitro and in vivo. Furthermore, we examined the osteoinductive potential of NSPTi implants by investigating the proliferation and differentiation of MC3T3-E1 preosteoblast cells. In vivo, the osteoinductive properties of NSPTi implants were assessed by radiographic evaluation, H&E staining, and Masson's trichrome staining. Results: In vitro, bacterial adhesion to the 2% NSPTi was significantly inhibited and <1% of adhered bacteria survived after 24 hours. In vitro, the average colony-forming units (CFU)/g ratios in the 2% NSPTi with 103 CFU MRSA and PAO-1 were 1.50±0.68 and 1.75±0.6, respectively. In the uncoated Ti groups, the ratios were 1.03±0.82×103 and 0.94±0.49×103, respectively. These results demonstrated that NSPTi implants had prominent antibacterial properties. Proliferation of MC3T3-E1 cells on the 2% NSPTi sample was 1.51, 1.78, and 2.22 times that on the uncoated Ti control after 3, 5, and 7 days' incubation, respectively. Furthermore, NSPTi implants promoted the maturation and differentiation of MC3T3-E1 cells. In vivo, NSPTi accelerated the formation of new bone while suppressing bacterial survival. Conclusion: NSPTi implants have simultaneous antibacterial and osteoinductive activities and therefore have the potential in clinical applications.

Caffeic Acid Phenethyl Ester Rescues Pulmonary Arterial Hypertension through the Inhibition of AKT/ERK-Dependent PDGF/HIF-1α In Vitro and In Vivo.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial proliferation and remodeling, resulting in a specific increase in right ventricle systolic pressure (RVSP) and, ultimately right ventricular failure. Recent studies have demonstrated that caffeic acid phenethyl ester (CAPE) exerts a protective role in NF-κB-mediated inflammatory diseases. However, the effect of CAPE on PAH remains to be elucidated. In this study, monocrotaline (MCT) was used to establish PAH in rats. Two weeks after the induction of PAH by MCT, CAPE was administrated by intraperitoneal injection once a day for two weeks. Pulmonary hemodynamic measurements and pulmonary artery morphological assessments were examined. Our results showed that administration of CAPE significantly suppressed MCT-induced vascular remodeling by decreasing the HIF-1α expression and PDGF-BB production, and improved in vivo RV systolic performance in rats. Furthermore, CAPE inhibits hypoxia- and PDGF-BB-induced HIF-1α expression by decreasing the activation of the AKT/ERK pathway, which results in the inhibition of human pulmonary artery smooth muscle cells (hPASMCs) proliferation and prevention of cells resistant to apoptosis. Overall, our data suggest that HIF-1α is regarded as an alternative target for CAPE in addition to NF-κB, and may represent a promising therapeutic agent for the treatment of PAH diseases.

Improving outcomes in chronic obstructive pulmonary disease by taking beta-blockers after acute myocardial infarction: a nationwide observational study.

ß-Blockers are a standard therapy for acute myocardial infarction (AMI) due to their better short-term and long-term outcomes. However, ß-blockers are often under-prescribed in chronic obstructive pulmonary disease (COPD) patients with AMI, since they are thought be related to bronchospasm. The aim of this study was to investigate the association between the usage of ß-blockers and the risk of mortality in COPD patients after first AMI via a nationwide, population-based cohort study. In this retrospective study, we identified 186,326 patients with AMI diagnosed between January 2000 and December 2012, 23,116 of whom had COPD, from the National Health Insurance Research Database. A total of 7609 patients (32.92%) were prescribed ß-blockers, while 15,507 were not. The ß-blocker patients were stratified into selective and non-selective ß-blocker groups. Multivariate Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) with 95% confidence intervals (95% CI). Selective ß-blocker use showed a reduced risk of mortality, as compared with patients without ß-blockers (HR 0.93; 95% CI 0.89-0.98; p < 0.01) while non-selective ß-blocker groups did not increase the risk of mortality compared to the patients without ß-blockers (HR 0.98; 95% CI 0.94-1.02; p = 0.38). In addition, the use of ß-blockers was found to be associated with a reduced risk of mortality in most stratified analyses which was seen particularly in males, patients aged 65 years and above, and in individuals with an array of comorbidities. These findings suggest that ß-blockers improve overall survival among COPD patients after first AMI.

Combination Therapy with Dipyridamole and Clopidogrel for Secondary Stroke Prevention in Aspirin-Intolerant Patients After Myocardial Infarction: Results of a Nationwide Case-Control Study.

BACKGROUND AND PURPOSE: Combination therapy with dipyridamole and clopidogrel in stroke prevention and long-term outcomes in aspirin-intolerant patients with acute myocardial infarction (AMI) and previous stroke are unknown. This nationwide study analyzed the impact of dipyridamole and clopidogrel on secondary stroke prevention and long-term outcomes in aspirin-intolerant stroke patients after AMI. METHODS: This was a nationwide, case-control study involving 186,112 first AMI patients, 78,607 of whom had a previous history of stroke. In the final analysis, we included 4637 patients taking clopidogrel alone and 208 patients using a combination of clopidogrel and dipyridamole. RESULTS: The 12-year survival rate was not different between clopidogrel and clopidogrel-dipyridamole groups (log-rank p = 0.6247). Furthermore, there were no differences in event-free survival after stroke (log-rank p = 0.6842), gastrointestinal (GI) bleeding (log-rank p = 0.9539), or intracerebral hemorrhage (ICH; log-rank p = 0.6191) between the two groups. Dipyridamole did not contribute significantly to AMI survival (hazard ratio 0.98, 95% confidence interval 0.84-1.15), and did not show benefits in any of the subgroups regardless of sex, age (younger or older than 75 years), comorbidities, percutaneous coronary intervention, or medications. CONCLUSION: No differences were observed in the 12-year survival rate between clopidogrel and clopidogrel-dipyridamole groups. The two groups had balanced event-free survival in recurrent stroke, ICH, GI bleeding, and myocardial infarction.

Comparison of long-term mortality in patients with acute myocardial infarction associated with or without sepsis.

OBJECTIVES: Although the association between systemic infection and cardiovascular events has been identified, uncertainty remains regarding the incidence and prognosis of sepsis in acute myocardial infarction (AMI). The purpose of this research was to assess the impact of sepsis on survival after first AMI. METHODS: This was a nationwide cohort study involving the analysis of data from the Taiwan National Health Insurance Research Database for the period 2000-2012, for patients with a primary diagnosis of first AMI. Among the 186112 prospective patients, sepsis was diagnosed in 13065 (7.0%). The propensity score matching technique was used to match 13065 controls to the patients with sepsis and AMI with similar baseline characteristics. Cox proportional hazards regression models, including sepsis, percutaneous coronary intervention (PCI), and comorbidities, were performed to further evaluate the different influences on the mortality risk in patients hospitalized for first AMI. RESULTS: Overall, the 12-year survival rate was lower in AMI patients with sepsis than in those without sepsis (log rank p-value <0.001); this was also shown in the different age and sex groups. The AMI patients with sepsis had a longer length of hospital stay than those without sepsis (32.5days vs. 11.74 days, p<0.001). In the Cox proportional hazards regression analysis, sepsis was an independent risk factor for mortality in patients after AMI (hazard ratio 1.78; 95% confidence interval 1.72-1.83). Interventional management with PCI or coronary artery bypass grafting improved survival in both the sepsis and non-sepsis patients after first AMI. CONCLUSIONS: In conclusion, sepsis significantly increased the mortality risk of patients after first AMI. PCI may improve the long-term survival of patients in comparison to those managed conservatively.

Upregulation of long noncoding RNA MEG3 inhibits the osteogenic differentiation of periodontal ligament cells.

OBJECTIVE: This study aims to discuss long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) function of regulating osteogenesis in human periodontal ligament cells (hPDLCs). METHODS: First, use of a mineralizing solution induced osteogenic differentiation of hPDLCs to establish a differentiated cell model. Through microarray analysis, we selected a lncRNA MEG3 with marked changes between differentiated and undifferentiated cells. The quantitative polymerase chain reaction was used to detect the MEG3 content and an enzyme-linked immunosorbent assay was used to detect changes in related proteins. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis was measured by flow cytometry. Alizarin red staining was also used to evaluate cells' osteogenic level. Finally, RNA-binding protein immunoprecipitation assays were conducted to further clarify the endogenous relationship between MEG3 and bone morphogenetic protein 2 ( BMP2) in hPDLCs. RESULTS: MEG3 was downregulated in osteogenic differentiation hPDLCs induced by mineralizing solution. Overexpression of MEG3 inhibited cell viability and increased cell apoptosis. MEG3 overexpression can reverse osteogenic differentiation induced by mineralizing solution. MEG3 can suppress BMP2 through interaction with heterogeneous nuclear ribonucleoprotein I. CONCLUSION: Upregulation of MEG3 inhibits the osteogenic differentiation of periodontal ligament cells by downregulating BMP2 expression.

MiRNA-218 regulates osteoclast differentiation and inflammation response in periodontitis rats through Mmp9.

Periodontitis is a multiple infection and inflammatory disease featured by connective tissue homeostasis loss, periodontal inflammation, and alveolar bone resorption. MicroRNAs (miRNAs) are involved in the mediation of a large scale of pathological processes. Here, we show that miRNA-218 provides protective effect on periodontitis via regulation of matrix metalloproteinase-9 (Mmp9). This pathway is aberrant in periodontium from rats with periodontitis and human periodontal ligament progenitor cells stimulated by lipopolysaccharide, with downregulation of miR-218 and higher levels of Mmp9 compared with periodontium from healthy rats and cells without stimulation. Overexpression of miR-218 can suppress the degradation of Collagen Types I and IV and dentin sialoprotein (DSP), attenuate osteoclast formation, and inhibit the secretion of proinflammatory cytokines. On the other hand, overexpression of Mmp9 promotes the degradation of Collagen Types I and IV and DSP as well as RANKL-induced osteoclast formation and elevates inflammatory factors levels. Furthermore, the inhibitory effect of miR-218 was prevented by rescuing the Mmp9 expression. In addition, we also have showed that miR-218 was able to attenuate bone resorption and inflammation in a periodontitis rat model. Collectively, our findings therefore suggest that miR-218 acts as a protective role in periodontitis through the regulation of Mmp9.

The Dipyridamole Added to Dual Antiplatelet Therapy in Cerebral Infarction After First Acute Myocardial Infarction: A Nationwide, Case-Control Study.

Background and Purpose: No previous study has compared the impact of dipyridamole-based triple antiplatelet therapy on secondary stroke prevention and long-term outcomes to that of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI) and previous stroke. This study aimed to evaluate the impact of dipyridamole added to DAPT on stroke prevention and long-term outcomes in patients with cerebral infarction after first AMI. Methods: This nationwide, case-control study included 75,789 patients with cerebral infarction after first AMI. A 1:4 propensity score matching ratio was adopted based on multiple variables. Finally, the data of 4,468 patients included in the DAPT group and 1,117 patients included in the Dipyridamole-DAPT group were analyzed. Primary outcome was overall survival. Secondary outcomes were cumulative event rate of recurrent MI or stroke, and cumulative intracerebral hemorrhage (ICH) and gastrointestinal bleeding rate. Results: Long-term survival rate was comparable between the two groups (log-rank P = 0.1117), regardless of sex analyses. However, after first year, DAPT subgroup revealed better survival over DAPT-dipyridamole subgroup (log-rank P = 0.0188). In age subgroup analysis, a lower survival rate was detected in younger patients from the Dipyridamole-DAPT group after first year (log-rank P = 0.0151), but no survival difference for older patients. No benefit of Dipyridamole-DAPT was detected for patients after AMI, regardless of the myocardial infarction type. DAPT was superior to Dipyridamole-DAPT in patients who underwent percutaneous coronary intervention (PCI) (log-rank P = 0.0153) and ST elevation myocardial infarction after first year (log-rank P = 0.0019). Dipyridamole-DAPT did not reduce cumulative event rate of recurrent MI or stroke in patients after AMI. Moreover, Dipyridamole-DAPT increased the cumulative ICH rate (log-rank P = 0.0026), but did not affect the cumulative event rate of gastrointestinal bleeding. In Cox analysis, dipyridamole did not improve long-term survival. Conclusions: This nationwide study showed that Dipyridamole-DAPT, compared with DAPT, did not improve long-term survival in patients with stroke after AMI, and was related to poor outcomes after 1 year. Dipyridamole-DAPT did not reduce recurrent rate of MI or stroke, but increased the ICH rate without impacting the incidence of gastrointestinal bleeding.