Cyclic guanosine-3′,5′-monophosphate (cGMP)-dependent protein kinase type I (cGKI aka PKG) is a major cardiac effector acting downstream of nitric oxide (NO)-sensitive soluble guanylyl cyclase (NO-GC) and natriuretic peptides (NPs), which signal through transmembrane guanylyl cyclases. Consistent with the wide distribution of the cGMP-generating guanylyl cyclases, cGKI, which usually elicits its cellular effects by direct phosphorylation of its targets, is present in multiple cardiac cell types including cardiomyocytes (CMs). Although numerous targets of cGMP/cGKI in heart were identified in the past, neither their exact patho-/physiological functions nor cell-type specific roles are clear. Herein we inform about the current knowledge on the signal transduction downstream of CM cGKI. We believe that better insights into the specific actions of cGMP and cGKI in these cells will help to guide future studies in the search for predictive biomarkers for the response to pharmacological cGMP pathway modulation. In addition, targets downstream of cGMP/cGKI may be exploited for refined and optimized diagnostic and therapeutic strategies in different types of heart disease and their causes. Importantly, key functions of these proteins and particularly sites of regulatory phosphorylation by cGKI should, at least in principle, remain intact even though upstream signaling via the second messenger cGMP is impaired or dysregulated in a stressed or diseased heart state.Adenoviral vectors are useful tools to manipulate a gene of interest in vitro and in vivo, including in the vascular system. The transduction efficiencies of adenoviral vectors in vascular cells such as endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are known to be lower than those in epithelial cell types. The effective entry for adenoviral vectors is primarily mediated through the coxsackievirus and adenovirus receptor (CAR) which has been shown to be expressed in both cell types. Cationic liposomes have been used to enhance adenovirus transduction efficiency in non-epithelial cells. Accordingly, the aim of this study is to obtain new information regarding differences in, transduction efficiencies, cationic liposome sensitivity, and CAR expression between ECs and VSMCs. Using cultured rat aortic ECs and VSMCs, here, we have compared transduction efficiency of adenovirus with or without inclusion of liposomes and CAR expression. A significant increase in basal transduction efficiency was observed in ECs compared to VSMCs. Cationic liposome polybrene enhanced transduction efficiency in VSMCs, whereas decreased efficiency was observed in ECs. Western blotting demonstrated expression of CAR in ECs but not VSMCs. Proteomic analysis as well as mouse aorta immunostaining further suggest significant expression of CAR in ECs but not in VSMCs. In conclusion, adenovirus can effectively transduce the gene of interest in aortic ECs likely due to abundant expression of CAR, whereas cationic liposomes such as polybrene enhance the transduction efficiency in VSMCs lacking CAR expression.Chrysin (CH) is the main ingredient of many medicinal plants. Our previous study showed that CH could suppress hypoxia-induced PASMC proliferation and alleviate chronic hypoxia-induced pulmonary hypertension (CHPH) by targeting SOCE- [Ca]i pathway. In this study, we investigated the effect of CH on MCT-induced pulmonary hypertension (MCTPH) and the mechanism behnd it. Results show that, in MCTPH model rats, 1) CH significantly reduced the enhancement of right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; 2) CH markedly suppressed the promotion of SOCE and [Ca]i in PASMCs and 3) CH obviously inhibited the MCT-upregulated PCNA, TRPC1, TRPC4 and TRPC6 expression in distal pulmonary arteries. These results demonstrate that CH likely alleviates MCTPH by targeting TRPC1,4,6-SOCE-[Ca]i pathway.BACKGROUND Add-on therapy with prostacyclin in pediatric refractory pulmonary hypertension poses a challenge, especially when considering continuous intravenous administration in younger children. A search for alternate routes of drug delivery has led to the clinical investigation of stable and long-acting prostacyclin analogues, such as subcutaneous treprostinil. We reported two pediatric cases of pulmonary hypertension treated with subcutaneous treprostinil and reviewed the literature on treprostinil use in children. METHOD The literature review used three electronic databases and a combination of terms (treprostinil, pediatric, pulmonary hypertension, prostanoid, etc.). We also searched for pediatric clinical trials on treprostinil registered on international clinical trial registries. RESULTS The reported cases highlighted the multifactorial nature of pulmonary hypertension in pediatrics a female child with a giant omphalocele, and intra and extracardiac shunts; and a male premature child with a congenital diaphragmatic hernia and long-term pulmonary hypertension. The literature review identified 19 studies reporting treprostinil use in 421 children with various types of pulmonary hypertension (groups 1 and 3). Subcutaneous treprostinil was the most administered formulation, at a mean dose of 40 ng/kg/min. Overall, 12 clinical trials on treprostinil for children with pulmonary hypertension were registered on the clinical trial registries. Most authors concluded that subcutaneous treprostinil was effective, well tolerated, and represented an alternative to intravenous epoprostenol. CONCLUSION Subcutaneous treprostinil may be a useful adjunct in the therapeutic algorithm for children with severe pulmonary hypertension, refractory to oral drugs, and after a complete check-up for all pulmonary hypertension etiologies.The pathogenesis of cardiorenal syndrome (CRS) is very complex, and currently there is no effective treatment for CRS. Higenamine (HI) has been shown to improve cardiac function in rats with heart failure. However, the role of higenamine in CRS remains unknown. Here, in vitro, higenamine treatment markedly reduced neonatal rat cardiac fibroblast (NCF) collagen synthesis and inhibited neonatal rat cardiac myocyte (NCM) hypertrophy. In our study, a rat model of type 2 cardiorenal syndrome was induced by left anterior descending coronary artery ligation combined with 5/6 subtotal nephrectomy (STNx). Higenamine treatment decreased serum creatinine (Scr), blood urea nitrogen (BUN) and brain natriuretic peptide (BNP) levels and was capable of improving left ventricular remodeling and systolic function in CRS rats, accompanied with decreased expression of transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA) and collagen I (Col1A1). Moreover, higenamine significantly inhibited the protein expression of phosphorylated apoptosis signal-regulated kinase 1 (p-ASK1) and downstream Mitogen-activated protein kinases (MAPK) (ERK, P38)/NF-κB in cardiorenal tissues of CRS rats and NCF/NCM cells. Our study demonstrated that higenamine improved cardiorenal function in CRS rats and attenuated heart and kidney fibrosis possibly via targeting ASK1/MAPK (ERK, P38)/NF-κB signaling pathway. This finding extends our knowledge on the role of higenamine in cardiorenal fibrosis, providing a potential target to prevent the progression of CRS.Traumatic and stressful events of childhood, known as adverse childhood experiences (ACEs), have been associated with numerous health outcomes. However, little is known about ACEs in atopic dermatitis (AD) patients. We sought to determine the relationship between ACEs and childhood AD. Data were analyzed from the Fragile Families and Child Wellbeing Study, a longitudinal birth cohort study that followed 4898 women and their children born in large US cities. Multivariable weighted logistic regression models adjusting for sociodemographics were constructed to determine the associations of ACEs with AD prevalence at ages 5, 9, and 15 years. Children who experienced 1 ACE (multivariable logistic regression; adjusted odds ratio [aOR], 1.42; 95% confidence interval [CI], 1.08-1.86), 2 ACEs (1.49; 95% CI, 1.10-2.02), or 3 or more ACEs (2.10; 95% CI, 1.52-2.89) had significantly increased odds of AD history compared with children without ACEs at age 5 years. Children who experienced 3 or more ACEs (1.48; 95% CI, 1.09-2.01) had significantly increased odds of AD history compared with children without ACEs at age 9 years. There were no significant associations between ACEs and history of AD at age 15 years. In conclusion, ACE exposures are related to childhood AD across time. Children who experience a greater number of ACEs have higher prevalence of AD.BACKGROUND Urushiol, the culprit allergen in Toxicodendron plants such as poison ivy, is an oily mixture of 15 and 17 carbon side chain alk-(en)-yl catechols. Recently, consumer products have been identified that contain Toxicodendron as an ingredient on their label; however, no studies have assessed whether urushiol is indeed present within these products. OBJECTIVE The aim of the study was to determine whether urushiol compounds are present in consumer products labeled as containing Toxicodendron species. METHODS Gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry were performed on 9 consumer products labeled as containing Toxicodendron species, including topical homeopathic remedies. Single ion monitoring gas chromatography-mass spectrometry was programmed in selective ion mode to detect 3-methylcatechol characteristic fragment ions of alk-(en)-yl catechols after silanization. Similarly, single ion monitoring liquid chromatography-tandem mass spectrometry was programmed to detect 4 urushiol pentadecylcatechols and 5 urushiol heptadecylcatechols using previously reported mass-to-charge ratios. RESULTS Gas chromatography-mass spectrometry detected alk-(en)-yl catechols in 67% (6/9) of the products tested. Liquid chromatography-tandem mass spectrometry detected multiple urushiol pentadecylcatechols and heptadecylcatechols in 44% (4/9) of the products tested. CONCLUSIONS Alk-(en)-yl catechols and multiple urushiols were detected in consumer products listing Toxicodendron species as an ingredient. Clinicians should be aware of these known allergenic ingredients in consumer products.BACKGROUND Allergic contact dermatitis to rubber accelerators in gloves has been well described in the literature. In response to this, glove manufacturers have recently marketed „accelerator-free” gloves. Little research has been done, to confirm whether these gloves are truly free from the accelerators known to cause contact dermatitis. OBJECTIVE The aim of the study was to verify use of accelerators in reportedly accelerator-free/low-dermatitis-potential gloves. METHODS A total of 16 commercially available medical gloves touted as „accelerator-free,” „sensitive,” or „low dermatitis potential” were obtained and analyzed via mass spectrometry (liquid chromatography heated electrospray ionization tandem mass spectrometry and liquid chromatography heated electrospray high-resolution tandem mass spectrometry) to determine whether any of the 9 known rubber accelerators were present (thiurams, carbamates, mercaptobenzothiazole, and diphenylguanidine). RESULTS Despite marketing claims to the contrary, all tested gloves had at least 1 accelerant detected.