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The spontaneous closure rate of patent ductus arteriosus (PDA) is high, and the necessity of early intervention is debated. Quantitative echocardiographic assessment of the intima in PDA has not been reported. This study evaluated intimal thickness growth in neonatal cases of PDA via echocardiography and investigated its correlation with clinical factors. Seventy-three neonates were enrolled, and echocardiography was performed three times within 24 h post-birth (first echo), 48 h after the first echo (second echo), and before discharge (third echo). According to PDA outcome, the neonates were divided into the PDA-open group (n = 18 cases), PDA-closure at second echo group (n = 32 cases), and non-PDA at first echo group (n = 23 cases). We measured the intimal thickness (IT1 and IT2 at first and second echo, respectively), lumen diameter of ductus arteriosus (D1 and D2 at first and second echo, respectively), IT1/D1 ratio, and intimal thickness growth rate (V). Correlations between echocardiographic indicators, perinatal factors, and clinical treatment were analyzed. On first echo, the PDA-open group showed a significantly lower IT1/D1 than the combined PDA-closure group (P  less then  0.05). Atuveciclib On second echo, the PDA-open group showed a significantly lower IT2 and V than the PDA-closure group as well as a significantly higher D2 (P  less then  0.05). Smaller gestational age correlated with a larger D2 but smaller IT2 and V (P  less then  0.05) and a higher level of respiratory support within 72 h post-birth correlated with a larger D2 and smaller IT 2 (P  less then  0.05). Increasing oxygen demand within 72 h of birth correlated with a larger D1 and D2 (P  less then  0.05). Echocardiographic assessment of intimal thickness growth in PDA may provide an approach for predicting spontaneous PDA closure, thereby guiding decision-making regarding early intervention.The heart-liver axis is of growing importance. Previous studies have identified independent association of liver dysfunction and fibrosis with adverse cardiac outcomes, but mechanistic pathways remain uncertain. We sought to understand the relations between the degree of hepatic fibrosis identified by the Fibrosis-4 (Fib-4) risk score and comprehensive cardiac MRI (CMR) measures of subclinical cardiac disease. We conducted a retrospective single-center cohort study of patients between 2011 and 2021. We identified consecutive patients who underwent a comprehensive CMR imaging protocol including contrast enhanced with stress/rest perfusion, and lacked pre-existing cardiovascular disease or perfusion abnormalities on CMR. We examined the association of hepatic fibrosis, using the Fib-4 score, with subclinical cardiac disease on CMR while adjusting for cardiometabolic traits. Given known associations of hepatic disease and coronary microvascular dysfunction, we prioritized analyses with the myocardial perfusion reserve index (MPRI), a marker of coronary microvascular function. Of the 66 patients in our study cohort, 54 were female (81%) and the mean age was 53.7 ± 15.3 years. We found that higher Fib-4 was associated with reduction in the MPRI (β [SE] - 1.12 [0.46], P = 0.02), after adjusting for cardiometabolic risk factors. Importantly, Fib-4 was not significantly associated with any other CMR phenotypes including measures of cardiac remodeling, inflammation, fibrosis, or dysfunction. We found evidence that hepatic fibrosis associated with coronary microvascular dysfunction, in the absence of overt associations with any other subclinical cardiac disease measures. These findings highlight a potentially important precursor pathway leading to development of subsequent heart-liver disease.Granulomatosis with polyangiitis is an anti-neutrophil cytoplasmic antibody-associated vasculitis that manifests in various ways by affecting the small-sized vessels in multiple organs. Acute pleuritis and pericarditis are both rare among the different manifestations of granulomatosis with polyangiitis. The symptoms in each of the organs are often apparent at the time of diagnosis and tend to diminish with treatment. Organ damage and progression of the disease during treatment are uncommon. We encountered a patient with granulomatosis with polyangiitis who, after starting intravenous methylprednisolone pulse therapy, concurrently developed acute pleuritis and pericarditis. The patient was a 47-year-old Japanese man with myalgia in whom kidney dysfunction, proteinase 3-anti-neutrophil cytoplasmic antibody positivity, and a lung mass were detected. Granulomatosis with polyangiitis was diagnosed pathologically from a lung and a kidney biopsy. Acute pleuritis and pericarditis, which developed after the first course of intravenous methylprednisolone pulse therapy, both resolved following the second course. The present report indicates that secondary serositis such as pleuritis and pericarditis can develop in patients with granulomatosis with polyangiitis even during glucocorticoid therapy.Stem  cell therapy for cardiac regeneration has been gaining traction as a possible intervention for the reduction of the burden associated with MI and heart failure. However, stem cell therapies have several shortcomings, including poor engraftment, limited improvements in cardiac function, and possible teratogenicity. Recently, extracellular vesicles (EVs) from stem cell sources have been explored as a novel therapy to regenerate the injured myocardium in several animal MI trials. In this systematic review and meta-analysis, we investigate the use of stem cell-derived EVs for cardiac repair preclinical trials in animal MI models. Cochrane Library, Medline, Embase, PubMed, Scopus and Web of Science and grey literature (Canadian Agency for Drugs, Technologies in Health, and Google Scholar) were searched through August 20, 2020 and 37 articles were included in the final analysis. The overall effect size observed in EV-treated small animals after MI for ejection fraction (EF) was 10.85 [95 %CI 8.79, 12.90] and for fractional shortening (FS) was 7.19 [95 %CI 5.43, 8.96] compared to control-treated animals. The most abundant stem cell source used were mesenchymal stem cells which showed robust improvements in EF and FS (MD = 11.89 [95 % CI 9.44, 14.34] and MD = 6.96 [95 % CI 4.97, 8.96], respectively). Significant publication bias was detected for EF and FS outcomes. This study supports the use of EVs derived from stem cells as a novel therapy for cardiac repair after MI. Further investigation in larger animal studies may be necessary before clinical trials.PROSPERO registration number CRD42019142218.During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study mechanisms of human neural development, disease modeling, and drug discovery in vitro. Especially in the field of Alzheimer's disease (AD), where this treatment is lacking, tremendous effort has been put into the investigation of molecular mechanisms behind this disease using induced pluripotent stem cell-based models. Numerous of these studies have found either novel regulatory mechanisms that could be exploited to develop relevant drugs for AD treatment or have already tested small molecules on in vitro cultures, directly demonstrating their effect on amelioration of AD-associated pathology. This review thus summarizes currently used differentiation strategies of induced pluripotent stem cells towards neuronal and glial cell types and cerebral organoids and their utilization in modeling AD and potential drug discovery.Rheumatoid arthritis (RA) is a chronic autoimmune joint disease that causes cartilage and bone damage or even disability, seriously endangering human health. Chronic synovial inflammation has been shown to play a vital role in disease sustainability. Therefore, downregulation of synovial inflammation is considered to be an effective discipline for RA therapy. Polyene phosphatidylcholine (PPC) is a hepatoprotective agent, which was observed to inhibit inflammation in macrophages and prevent collagen-induced arthritis (CIA) of rats in our previous study. However, the underlying mechanism remains unclear. The present study further reported that PPC can inhibit synovial inflammation. In lipopolysaccharide (LPS)-stimulated primary synovial fibroblasts (SFs) of mice, PPC significantly decreased pro-inflammatory cytokines production while increasing anti-inflammatory cytokines level. In this process, PPC downregulated the expression of TLR-2 and their downstream signaling molecules such as MyD88, p-ERK1/2, p-JNK1/2, and p-P38 in MAPK pathway and p-IκBα and NF-κB-p65 in NF-κB pathway. Moreover, the inhibitory effect of PPC on the above molecules and cytokines was weakened after pre-treatment with TLR-2 agonist Pam3CSK4. In addition, PPC lost its anti-inflammatory effect and its suppressing capability on MAPK and NF-κB pathways in TLR-2-/- primary SFs after exposure to LPS. Collectively, this study demonstrated that PPC can alleviate synovial inflammation through TLR-2-mediated MAPK and NF-κB pathways, which can be proposed to be a potential drug candidate for RA prevention.

The binding of high-density lipoprotein (HDL) to its primary receptor, scavenger receptor class B type 1 (SR-B1), is critical for lowering plasma cholesterol levels and reducing cardiovascular disease risk. This review provides novel insights into how the structural elements of SR-B1 drive efficient function with an emphasis on bidirectional cholesterol transport.

We have generated a new homology model of full-length human SR-B1 based on the recent resolution of the partial structures of other class B scavenger receptors. Interrogating this model against previously published observations allows us to generate structurally informed hypotheses about SR-B1's ability to mediate HDL-cholesterol (HDL-C) transport. Furthermore, we provide a structural perspective as to why human variants of SR-B1 may result in impaired HDL-C clearance. A comprehensive understanding of SR-B1's structure-function relationships is critical to the development of therapeutic agents targeting SR-B1 and modulating cardiovascular disease risk.

We have generated a new homology model of full-length human SR-B1 based on the recent resolution of the partial structures of other class B scavenger receptors. Interrogating this model against previously published observations allows us to generate structurally informed hypotheses about SR-B1's ability to mediate HDL-cholesterol (HDL-C) transport. Furthermore, we provide a structural perspective as to why human variants of SR-B1 may result in impaired HDL-C clearance. A comprehensive understanding of SR-B1's structure-function relationships is critical to the development of therapeutic agents targeting SR-B1 and modulating cardiovascular disease risk.

The accumulation of triglyceride-rich lipoproteins (TRLs) in plasma in patients with familial chylomicronaemia syndrome (FCS) or severe hypertriglyceridemia is associated with an increased risk of potentially life-threatening pancreatitis. Elevated TRL levels have also been suggested to contribute to atherosclerotic cardiovascular disease (ASCVD). This review provides the latest progress that has been made in this field of research.

Apolipoprotein C-III and angiopoietin-like protein 3 play key roles in the metabolism of TRLs. Targeting their production in the liver or their presence in the circulation effectively reduces triglycerides in patients with FCS or severe hypertriglyceridemia. Attempts to reduce triglyceride synthesis in the small intestine have been halted. Early studies with a fibroblast growth factor 21 agonist have shown to reduce plasma triglycerides and hepatic steatosis and improve glucose homeostasis. New drugs have recently been shown to effectively reduce plasma triglycerides which render hope for treating the risk of pancreatitis.