Efficacy and safety of omega-3-acid ethyl acetate 90 capsules in severe hypertriglyceridemia: A randomized, controlled, multicenter study.

Omega-3-acid ethyl acetate 90 capsules (containing 465 mg of eicosapentaenoic acid and 375 mg docosahexaenoic acid) is composed of highly purified omega-3 polyunsaturated fatty acid (PUFA) ethyl esters, whose lipid-lowering effect for severe hypertriglyceridemia (HTG) treatment is unclear. This study aimed to evaluate the efficacy and safety of omega-3-acid ethyl acetate 90 capsules in patients with severe HTG. In this randomized, double-blind, placebo-controlled, multicenter study, 239 patients with severe HTG were enrolled and randomized (1:1) into omega-3 group (N = 122) and placebo group (N = 117) to receive 12-week corresponding treatments. Lipid-related indexes were obtained at treatment initiation (W0), 4 weeks (W4), W8, and W12 after treatment. Adverse events and adverse drug reactions were recorded. Triacylglycerols (TAG), total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), and apolipoprotein C-III (Apo C-III) at W4, W8, and W12 were decreased in the omega-3 group versus the placebo group (all p < 0.05). Moreover, the percentage changes of TAG, TC, non-HDL-C, and VLDL-C from W0 to W4, W8, and W12, and the percentage change of Apo C-III from W0 to W4 and W8, were more obvious in the omega-3 group compared with the placebo group (all p < 0.05). However, no difference was observed in the percentage changes of HDL-C, low-density lipoprotein cholesterol (LDL-C), and LDL-C/HDL-C ratio during follow-up between groups (all p > 0.05). Additionally, there was no discrepancy in adverse events and adverse drug reactions between groups (all p > 0.05). Omega-3-acid ethyl acetate 90 capsules exhibit satisfied lipid-lowering effect with tolerable safety profile in patients with severe HTG.

Case report: Pulmonary artery sarcoma diagnosed through rare brain metastases.

We present the case of a 33-year-old male referred across several hospitals because of suspected chronic thromboembolic pulmonary hypertension (CTEPH). Initially admitted in October 2022 for a recurrent, severe cough and diagnosed with CTEPH, he received anticoagulant therapy. However, his symptoms worsened, necessitating a transfer to another facility for thrombolysis treatment. Following an episode of syncope, an MRI scan revealed a metastatic brain tumor. Subsequently, he experienced a third transfer to our hospital, emergency surgery was performed to alleviate cerebral edema and excise a lesion in the left frontal lobe. Postoperative pathology was inconclusive, but a multidisciplinary team meeting, aided by experienced radiologists, eventually confirmed a diagnosis of pulmonary artery sarcoma (PAS) with systemic metastases. This case underscores the necessity of promptly ruling out PAS in patients presenting with significant emboli in the central pulmonary arteries and suggests early referral to specialized centers for suspected cases.

Advances in ß-Diketocyclisation of Curcumin Derivatives and their Antitumor Activity.

Curcumin, derived from the popular spice turmeric, is a pharmacologically active polyphenol. Curcumin's therapeutic activity has been extensively studied in recent decades, with reports implicating curcumin in many biological activities, particularly, its significant anticancer activity. However, its potential as an oral administration product is hampered by poor bioavailability, which is associated with a variety of factors, including low water solubility, poor intestinal permeability, instability, and degradation at alkaline pH. To improve its bioavailability, modifying ß-diketone curcumin with heterocycles, such as pyrazole, isoxazole and triazole is a powerful strategy. Derivatives are synthesized while maintaining the basic skeleton of curcumin. The ß-diketone cyclized curcumin derivatives are regulators of multiple molecular targets, which play vital roles in a variety of cellular pathways. In some literatures, structurally modified curcumin derivatives have been compared with curcumin, and the former has enhanced biological activity, improved water solubility and stability. Therefore, the scope of this review is to report the most recently synthesized heterocyclic derivatives and to classify them according to their chemical structures. Several of the most important and effective compounds are reviewed by introducing different active groups into the ß-diketone position to achieve better therapeutic efficacy and bioavailability.

Pediatric restrictive cardiomyopathy: a case report.

Restrictive cardiomyopathy (RCM) is a rare childhood cardiomyopathy that is a challenging diagnostic problem for clinicians. We describe a case of an 8-year-old girl with a 2-year history of shortness of breath on exertion. Electrocardiogram and echocardiography showed biatrial enlargement, while cardiac magnetic resonance showed biatrial dilation and normal pericardial thickness. Left and right heart catheterization revealed a left ventricular (LV) end-diastolic pressure (EDP) of 20 mmHg, right ventricular (RV) EDP of 13 mmHg, and pulmonary arterial systolic pressure of 51 mmHg. LV and RV pressure traces showed that LV and RV pressures moved concordantly with respiration, and that the systolic area index was 0.98. Cardiac catheterization data were therefore supportive of RCM. Next-generation sequencing identified a heterozygous variant of the troponin I gene (TNNI3; c.574C>T). Combining these findings led to a diagnosis of RCM. The patient's parents chose conservative treatment, but at the 12-month follow-up she died of worsening heart failure and cerebral infarction. This case emphasizes the need for cardiac catheterization and genetic testing in RCM, and suggests that anticoagulants should be recommended to reduce the risk of thromboembolic events.

Human Plasma IgG N-Glycome Profiles Reveal a Proinflammatory Phenotype in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: The pathological mechanism of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood, and inflammation has been reported to be one of its etiological factors. IgG regulates systemic inflammatory homeostasis, primarily through its N-glycans. Little is known about IgG N-glycosylation in CTEPH. We aimed to map the IgG N-glycome of CTEPH to provide new insights into its pathogenesis and discover novel markers and therapies. METHODS: We characterized the plasma IgG N-glycome of patients with CTEPH in a discovery cohort and validated our results in an independent validation cohort using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Thereafter, we correlated IgG N-glycans with clinical parameters and circulating inflammatory cytokines in patients with CTEPH. Furthermore, we determined IgG N-glycan quantitative trait loci in CTEPH to reveal partial mechanisms underlying glycan changes. RESULTS: Decreased IgG galactosylation representing a proinflammatory phenotype was found in CTEPH. The distribution of IgG galactosylation showed a strong association with NT-proBNP (N-terminal pro-B-type natriuretic peptide) in CTEPH. In line with the glycomic findings, IgG pro-/anti-inflammatory N-glycans correlated well with a series of inflammatory markers and gene loci that have been reported to be involved in the regulation of these glycans or inflammatory immune responses. CONCLUSIONS: This is the first study to reveal the full signature of the IgG N-glycome of a proinflammatory phenotype and the genes involved in its regulation in CTEPH. Plasma IgG galactosylation may be useful for evaluating the inflammatory state in patients with CTEPH; however, this requires further validation. This study improves our understanding of the mechanisms underlying CTEPH inflammation from the perspective of glycomics.

19F MRI-fluorescence imaging dual-modal cell tracking with partially fluorinated nanoemulsions.

As a noninvasive "hot-spot" imaging technology, fluorine-19 magnetic resonance imaging (19F MRI) has been extensively used in cell tracking. However, the peculiar physicochemical properties of perfluorocarbons (PFCs), the most commonly used 19F MRI agents, sometimes cause low sensitivity, poor cell uptake, and misleading results. In this study, a partially fluorinated agent, perfluoro-tert-butyl benzyl ether, was used to formulate a 19F MRI-fluorescence imaging (FLI) dual-modal nanoemulsion for cell tracking. Compared with PFCs, the partially fluorinated agent showed considerably improved physicochemical properties, such as lower density, shorter longitudinal relaxation times, and higher solubility to fluorophores, while maintaining high 19F MRI sensitivity. After being formulated into stable, monodisperse, and paramagnetic Fe3+-promoted nanoemulsions, the partially fluorinated agent was used in 19F MRI-FLI dual imaging tracking of lung cancer A549 cells and macrophages in an inflammation mouse model.

Diversified Shifts in the Cross Talk between Members of the Gut Microbiota and Development of Coronary Artery Diseases.

Coronary artery disease (CAD) is one of leading causes of mortality worldwide. Studies on roles that the gut microbiota plays in development of atherosclerosis or acute myocardial infarction (AMI) have been widely reported. However, the gut microbiota is affected by many factors, including age, body mass index (BMI), and hypertension, that lead to high CAD risk. However, the associations between gut microbiota and CAD development or other CAD risk factors remain unexplored. Here, we performed a 16S RNA gene sequencing analysis of 306 fecal samples collected from patients with mild coronary stenosis (MCS; n = 36), stable angina (SA; n = 91), unstable angina (UA; n = 48), and acute myocardial infarction (AMI; n = 66) and 65 non-CAD controls. Using a noise-corrected method based on principal-component analysis (PCA) and the random forest algorithm, we identified the interference with gut microbial profiling of multiple factors (including age, gender, BMI, and hypertension) that potentially contributed significantly to the development of CAD. After correction of noise interference from certain interfering factors, we found consistent indicator microbiota organisms (such as Vampirovibrio, Ruminococcus, and Eisenbergiella) associated with the presence of MCS, SA, and AMI. Establishment of a diagnostic model revealed better performance in early CAD than clinical indexes with indicator microbes. Furthermore, indicator microbes can improve the accuracy of clinical indexes for the diagnosis of AMI. Additionally, we found that the microbial indicators of AMI Sporobacter and Eisenbergiella showed consistent positive and negative correlations to the clinical indexes creatine kinase (CK) and hemoglobin (Hb), respectively. As a control indicator of AMI, Dorea was negatively correlated with CK but positively correlated with Hb. IMPORTANCE Our study discovered the effect of confounding factors on gut microbial variations and identified gut microbial indicators possibly associated with the CAD development after noise correction. Our discovered indicator microbes may have potential for diagnosis or therapy of cardiovascular disorders.

p38 MAPK Endogenous Inhibition Improves Neurological Deficits in Global Cerebral Ischemia/Reperfusion Mice.

Cerebral ischemia/reperfusion (I/R) injury is a complex pathophysiological process that can lead to neurological function damage and the formation of cerebral infarction. The p38 MAPK pathway has attracted considerable attention in cerebral I/R injury (IRI), but little research has been carried out on its direct role in vivo. In this study, to observe the effects of p38 MAPK endogenous inhibition on cerebral IRI, p38 heterozygous knockdown (p38KI/+) mice were used. We hypothesized that p38 signaling might be involved in I/R injury and neurological damage reduction and that neurological behavioral deficits improve when p38 MAPK is inhibited. First, we examined the neurological damage and neurological behavioral deficit effects of I/R injury in WT mice. Cerebral I/R injury was induced by the bilateral common carotid artery occlusion (BCCAO) method. The cerebral infarction area and volume were assessed and analyzed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. p38 MAPK and caspase-3 were detected by western blotting. Neuronal apoptosis was measured using TUNEL staining. Neurological deficits were detected by behavioral testing. Furthermore, to assess whether these neuroprotective effects occurred when p38 MAPK was inhibited, p38 heterozygous knockdown (p38KI/+) mice were used. We found that p38 MAPK endogenous inhibition rescued hippocampal cell apoptosis, reduced ischemic penumbra, and improved neurological behavioral deficits. These findings showed that p38 MAPK endogenous inhibition had a neuroprotective effect on IRI and that p38 MAPK may be a potential therapeutic target for cerebral IRI.

Pulmonary Hypertension in a Patient With Kartagener's Syndrome and a Novel Homozygous Nonsense Mutation in CCDC40 Gene: A Case Report.

Kartagener's syndrome is a subgroup of primary ciliary dyskinesia (PCD), a genetically heterogeneous condition characterised by sinusitis, bronchiectasis, and situs in versus. Genetic testing has importance for their diagnosis. Here, we report a chinese patient with Kartagener's syndrome. Transthoracic echocardiography showed severely elevated right ventricular systolic pressure. Right heart catheterisation demonstrated a pre-capillary pulmonary hypertension. Whole-exome sequencing indicated that she had a novel homozygous nonsense mutation, c.2845C > T, p.Gln949*, in exon 18 of CCDC40 and a heterozygotic mutation, c.73G > A, p.Ala25Thr, in exon 1 of DNAH11. She was diagnosed as Kartagener's syndrome with pulmonary hypertension. Her symptoms improved significantly by treatment of antibiotics, expectorant drugs, bronchodilators, and oxygen therapy treatment. Our findings extend the mutation spectrum of CCDC40 gene related Kartagener's syndrome, which is very important for gene diagnosis of the disease.

Cierre percutáneo de una enorme fístula arteriovenosa pulmonar / Transcatheter closure of a huge pulmonary arteriovenous fistula

No disponible

p38 MAPK Inhibition Improves Synaptic Plasticity and Memory in Angiotensin II-dependent Hypertensive Mice.

The pathogenesis of hypertension-related cognitive impairment has not been sufficiently clarified, new molecular targets are needed. p38 MAPK pathway plays an important role in hypertensive target organ damage. Activated p38 MAPK was seen in AD brain tissue. In this study, we found that long-term potentiation (LTP) of hippocampal CA1 was decreased, the density of the dendritic spines on the CA1 pyramidal cells was reduced, the p-p38 protein expression in hippocampus was elevated, and cognitive function was impaired in angiotensin II-dependent hypertensive C57BL/6 mice. In vivo, using a p38 heterozygous knockdown mice (p38(KI/+)) model, we showed that knockdown of p38 MAPK in hippocampus leads to the improvement of cognitive function and hippocampal synaptic plasticity in angiotensin II-dependent p38(KI/+) hypertensive mice. In vitro, LTP was improved in hippocampal slices from C57BL/6 hypertensive mice by treatment with p38MAPK inhibitor SKF86002. Our data demonstrated that p38 MAPK may be a potential therapeutic target for hypertension-related cognitive dysfunction.