A method for investigating spatiotemporal growth patterns at cell and tissue levels during C-looping in the embryonic chick heart.

We developed a workflow using multi-scale and multi-disciplinary experimental and computational approaches to analyze C-looping (the first phase of cardiac looping) of the chick across four developing hearts. We provide the first 3D datasets for the C-looping heart with cell to organism level information, including datasets of heart images and segmented myocardial cells within the heart. We used these datasets to investigate, as a proof-of-concept, the differential spatiotemporal patterns of growth at both the cellular and tissue levels, and demonstrate how geometrical changes of C-looping at the tissue level are linked to growth features at the cellular level. Our methodological pipeline provides preliminary results for qualitative and quantitative evidence of various cellular and tissue features as potential candidates regarding the mechanism of C-looping. This pipeline can be used and extended in future studies to include larger specimen samples for detailed analyses of, and potentially new insights into, cardiac C-looping.

An integrative multiscale view of early cardiac looping.

The heart is the first organ to form and function during the development of an embryo. Heart development consists of a series of events believed to be highly conserved in vertebrates. Development of heart begins with the formation of the cardiac fields followed by a linear heart tube formation. The straight heart tube then undergoes a ventral bending prior to further bending and helical torsion to form a looped heart. The looping phase is then followed by ballooning, septation, and valve formation giving rise to a four-chambered heart in avians and mammals. The looping phase plays a central role in heart development. Successful looping is essential for proper alignment of the future cardiac chambers and tracts. As aberrant looping results in various congenital heart diseases, the mechanisms of cardiac looping have been studied for several decades by various disciplines. Many groups have studied anatomy, biology, genetics, and mechanical processes during heart looping, and have proposed multiple mechanisms. Computational modeling approaches have been utilized to examine the proposed mechanisms of the looping process. Still, the exact underlying mechanism(s) controlling the looping phase remain poorly understood. Although further experimental measurements are obviously still required, the need for more integrative computational modeling approaches is also apparent in order to make sense of the vast amount of experimental data and the complexity of multiscale developmental systems. Indeed, there needs to be an iterative interaction between experimentation and modeling in order to properly find the gap in the existing data and to validate proposed hypotheses. This article is categorized under: Cardiovascular Diseases > Genetics/Genomics/Epigenetics Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Molecular and Cellular Physiology.

The SPARC DRC: Building a Resource for the Autonomic Nervous System Community.

The Data and Resource Center (DRC) of the NIH-funded SPARC program is developing databases, connectivity maps, and simulation tools for the mammalian autonomic nervous system. The experimental data and mathematical models supplied to the DRC by the SPARC consortium are curated, annotated and semantically linked via a single knowledgebase. A data portal has been developed that allows discovery of data and models both via semantic search and via an interface that includes Google Map-like 2D flatmaps for displaying connectivity, and 3D anatomical organ scaffolds that provide a common coordinate framework for cross-species comparisons. We discuss examples that illustrate the data pipeline, which includes data upload, curation, segmentation (for image data), registration against the flatmaps and scaffolds, and finally display via the web portal, including the link to freely available online computational facilities that will enable neuromodulation hypotheses to be investigated by the autonomic neuroscience community and device manufacturers.

The association of endothelin-1 gene polymorphism and its plasma levels with hypertension and coronary atherosclerosis.

INTRODUCTION: Endothelin-1 (ET-1) is the most potent among all vasoconstrictors, and its association with cardiovascular diseases has been reported before. Our aim was to investigate the association of ET-1 plasma level and its gene polymorphisms (rs5370 and rs10478694) with hypertension and coronary atherosclerosis (CA). MATERIAL AND METHODS: This study was carried out on 128 women and 132 men, who were divided into 4 groups: hypertensive without atherosclerosis (H+A-); hypertensive with atherosclerosis (H+A+); non-hypertensive with atherosclerosis (H-A+); and non-hypertensive without atherosclerosis (control group). Endothelin-1 plasma levels were measured by ELISA, and gene polymorphisms were detected by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) methods. Coronary artery diseases (CAD) were then defined based on angiography data. RESULTS: The ET-1 plasma level was significantly higher in the H+A+ group in comparison with the other groups, especially H+A-. Comparing people with CA and those without it, the highest frequency level of the T allele of rs5370 was found in people with CA. Significantly higher frequencies of the 3A allele were detected in hypertensive patients in comparison with non-hypertensive individuals, when analyzing rs10478694. CONCLUSIONS: Endothelin-1 plasma level shows a direct association with the risk of CA development. The T allele of rs5370 can be regarded as a risk factor for CA development. The 3A allele of rs10478694 can be associated with the risk of hypertension; therefore, it can be concluded that ET-1 and its gene polymorphisms play an important role in CA development and hypertension observed in the south-eastern populations of Iran.

Atorvastatin, losartan and captopril may upregulate IL-22 in hypertension and coronary artery disease; the role of gene polymorphism.

AIMS: Interleukin-22 (IL-22) may be considered as an important cytokine in maintenance and progression of hypertension and coronary artery disease (CAD). The aim of the present study was to investigate the effect of treatment of hypertension and CAD on serum levels of IL-22 and the possible association of IL-22-rs1179251 gene polymorphism with hypertension and CAD. MATERIALS AND METHODS: A total of 286 subjects with suspected CAD were enrolled. Serum levels and gene polymorphism of IL-22 were investigated in hypertensive patients with no CAD (H-Tens), hypertensive patients with CAD (CAD + H-Tens); 3), CAD patients with no hypertension (CAD); and non-hypertensive with no CAD subjects as a control group (Ctr). The patients received routine medications for hypertension and CAD. Serum IL-22 levels and IL-22-rs1179251 gene polymorphism were evaluated using ELISA and RFLP-/PCR techniques, respectively. KEY FINDINGS: Findings demonstrated that there were significantly higher levels of IL-22 in case groups (H-Tens, CAD + H-Tens, and CAD) compared to the Ctr group (P = 0.001, P = 0.014, and P < 0.001, respectively). Moreover, atorvastatin, losartan and captopril were administered significantly more in patients compared to the Ctr group. The results indicated a decreased risk of CAD + H-Tens of rs1179251 dominant genetic model (OR = 0.324; 95% CI = 0.121-0.873; P = 0.026). SIGNIFICANCE: Atorvastatin, losartan and captopril may be led to upregulation of IL-22 in CAD and hypertensive patients. Meanwhile, higher levels of circulating IL-22 could contribute to alleviating the hypertension and CAD conditions. The G allele of IL-22 rs1179251 may be a protective factor for concomitant hypertension and CAD.

Correction: Atorvastatin, Losartan and Captopril Lead to Upregulation of TGF-ß, and Downregulation of IL-6 in Coronary Artery Disease and Hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0168312.].

Atorvastatin, Losartan and Captopril Lead to Upregulation of TGF-ß, and Downregulation of IL-6 in Coronary Artery Disease and Hypertension.

INTRODUCTION: Coronary artery disease (CAD) and hypertension are the main reasons of ischemic heart diseases (IHDs). Cytokines as the small glycoproteins are the main arm of immune system and manipulate all of the cardiovascular diseases. The aim of the current study was to examine the effects of treatment of hypertension and CAD on serum levels of IL-6, IL-8, TGF-ß and TNF-α. MATERIAL AND METHODS: This interventional study was performed on the patients with hypertension without CAD (group 1), hypertension and CAD (group 2), CAD but not hypertension (group 3) and without hypertension and CAD as controls (group 4). The patients received routine treatment for hypertension and CAD. Serum levels of IL-6, IL-8, TGF-ß and TNF-α were analyzed in the groups treated with various drugs, using ELISA technique. RESULTS: With regard to the medications, Atorvastatin, Losartan and Captopril were administered more in patients (groups 1, 2 and 3) than the patients without hypertension and CAD. The results revealed that serum levels of TGF-ß and IL-6 were significantly increased and decreased, respectively, in the groups 1, 2 and 3 when compared to group 4. Serum levels of TGF-ß were also increased in females in comparison to males in the group 4. DISCUSSION: According to the results it seems that Atorvastatin, Losartan and Captopril have reduced inflammation in in vivo conditions via downregulation of IL-6 and upregulation of TGF-ß.

Cytotoxic Effects of the Ethanol Bane Skin Extract in Human Prostate Cancer Pc3 Cells.

BACKGROUND: It is extensively supposed that vegetarian diet could affect cancer progress and increase the influence of formal chemotherapy. OBJECTIVES: The present study was designed to determine the effect of the ethanol Bane skin extract against chemo resistant prostate cancer PC3 cells. MATERIALS AND METHODS: PC3 and L929 cells were cultivated and then incubated in the ethanol Bane skin extract with various concentrations of 0.78, 1.5, 3.13, 6.25, 12.5 mg/mL in 3 times 24, 48, 72 hours. Cytotoxic effect of the ethanol Bane skin extract on PC3 and L929 cells was examined by MTT assay after 24, 48, and 72 hours. Morphology of PC3 cells was evaluated by Gimsa staining. RESULTS: The ethanol Bane skin extract inhibited proliferation and caused cell death with IC50 values of 2.8 mg/mL on PC3 cells and the IC50 was 6.1 mg/mL on l929 cells. Morphological changes and apoptotic bodies were observed in PC3 cells faced with the ethanol Bane skin extract by staining with Gimsa. CONCLUSIONS: The ethanol Bane skin extract could repress the growth of PC3 cell line. This inhibitory effect of the Bane extract depended on the dose and the time on PC3. The result of this study shows that the ethanol Bane skin extract includes photochemical and inhibitory function against proliferation and inducer of apoptosis in human prostate cancer PC3 cells and also has less cytotoxic effect on l929 than PC3 cells. The ethanol Bane skin extract might be a good candidate for the new herbal anticancer drug.

Knowledge of Dentistry, Medicine, and Pharmacy Students about Psychedelic Drugs in Kerman University of Medical Sciences.

BACKGROUND: Psychedelic drugs can cause one to get out of normal status and permanent cerebral defects, via affecting central nervous system. Consumption of theses drugs seems to be increasing nowadays especially among the youth and university educated population. We conducted a study to evaluate the awareness of medical science students of Kerman University of medical science who are going to be the future medical population. METHODS: This cross-sectional study was carried out on 471 of students of medicine, dentistry and pharmacy which were in the first to forth year of their education about psychedelic drugs (Ecstasy, LSD, Ice, crack and Yaba). To evaluate the students' awareness of drugs we used questionnaire with reliability and validity proven via pilot study. Statistics analysis was performed using SPSS13 software. FINDINGS: Average of their age was 3.2 ± 20.4. Overall among the students, 56.7% were in the low level of insight, 34.3% in medium and 6.9% in good level and 2.2% had best insight of the drugs. Also only 32.2% of students had the full information about the name of drug, 25.7 % had information about the form of them, 24% about the addiction with them, 7% about their complication and only 5% about the origin of drugs. The information about all psychedelic drugs was higher among pharmacy students, students of the third year and males. CONCLUSION: Our study showed a low insight about psychedelic drugs like Ecstasy, LSD, Ice, Crack, and Yaba among the students. According to this lack of information of these groups, it is suggested that educational courses about the complication, signs and symptoms of these drugs be held.