Ischemic Preconditioning and Postconditioning Protect the Heart by Preserving the Mitochondrial Network

BACKGROUND: Mitochondria fuse to form elongated networks which are more tolerable to stress and injury. Ischemic pre- and postconditioning (IPC and IPost, respectively) are established cardioprotective strategies in the preclinical setting. Whether IPC and IPost modulates mitochondrial morphology is unknown. We hypothesize that the protective effects of IPC and IPost may be conferred via preservation of mitochondrial network. METHODS: IPC and IPost were applied to the H9c2 rat myoblast cells, isolated adult primary murine cardiomyocytes, and the Langendorff-isolated perfused rat hearts. The effects of IPC and IPost on cardiac cell death following ischemia-reperfusion injury (IRI), mitochondrial morphology, and gene expression of mitochondrial-shaping proteins were investigated. RESULTS: IPC and IPost successfully reduced cardiac cell death and myocardial infarct size. IPC and IPost maintained the mitochondrial network in both H9c2 and isolated adult primary murine cardiomyocytes. 2D-length measurement of the 3 mitochondrial subpopulations showed that IPC and IPost significantly increased the length of interfibrillar mitochondria (IFM). Gene expression of the pro-fusion protein, Mfn1, was significantly increased by IPC, while the pro-fission protein, Drp1, was significantly reduced by IPost in the H9c2 cells. In the primary cardiomyocytes, gene expression of both Mfn1 and Mfn2 were significantly upregulated by IPC and IPost, while Drp1 was significantly downregulated by IPost. In the Langendorff-isolated perfused heart, gene expression of Drp1 was significantly downregulated by both IPC and IPost. CONCLUSION: IPC and IPost-mediated upregulation of pro-fusion proteins (Mfn1 and Mfn2) and downregulation of pro-fission (Drp1) promote maintenance of the interconnected mitochondrial network, ultimately conferring cardioprotection against IRI

Chronic inhibition, self-control and eating behavior: test of a 'resource depletion' model

The current research tested the hypothesis that individuals engaged in long-term efforts to limit food intake (e.g., individuals with high eating restraint) would have reduced capacity to regulate eating when self-control resources are limited. In the current research, body mass index (BMI) was used as a proxy for eating restraint based on the assumption that individuals with high BMI would have elevated levels of chronic eating restraint. A preliminary study (Study 1) aimed to provide evidence for the assumed relationship between eating restraint and BMI. Participants (N = 72) categorized into high or normal-range BMI groups completed the eating restraint scale. Consistent with the hypothesis, results revealed significantly higher scores on the weight fluctuation and concern for dieting subscales of the restraint scale among participants in the high BMI group compared to the normal-range BMI group. The main study (Study 2) aimed to test the hypothesized interactive effect of BMI and diminished self-control resources on eating behavior. Participants (N = 83) classified as having high or normal-range BMI were randomly allocated to receive a challenging counting task that depleted self-control resources (ego-depletion condition) or a non-depleting control task (no depletion condition). Participants then engaged in a second task in which required tasting and rating tempting cookies and candies. Amount of food consumed during the taste-and-rate task constituted the behavioral dependent measure. Regression analyses revealed a significant interaction effect of these variables on amount of food eaten in the taste-and-rate task. Individuals with high BMI had reduced capacity to regulate eating under conditions of self-control resource depletion as predicted. The interactive effects of BMI and self-control resource depletion on eating behavior were independent of trait self-control. Results extend knowledge of the role of self-control in regulating eating behavior and provide support for a limited-resource model of self-control. © 2013 Hagger et al

Friendship quality and gender differences in association with cyberbullying involvement and psychological well-being

Current literature has documented the detrimental effects of cyberbullying which include a range of internalising and externalising problems for those involved. Although critical, this research can sometimes ignore social-ecological aspects of a child's life that can potentially 'buffer' the negative psychological effects of such involvement. With this in mind, this cross-sectional investigation of 12-16 year olds [M(SD): 13.5(1) years] in Ireland focused on the role of friendship quality and gender in association with cyberbullying involvement and psychological well-being (N= 2410). The Cyberbullying and Online Aggression Scale was used to measure cyber perpetration and victimisation. A modified version of the Cambridge Friendship Questionnaire was included to investigate peer friendship quality. Finally, the Moods and Feeling Questionnaire and the Strengths and Difficulties Questionnaire were chosen to provide a measurement of psychological well-being. Prevalence rates for various types of cyberbullying roles (cyber bullies, victims and bully/victims) are presented, as well as differences for psychological well-being, friendship quality and cyberbullying involvement. In addition, regression models were used to determine the associations between gender, age, friendship quality and involvement in cyberbullying with psychological well-being. The results are considered in terms of the current literature and directions for future research are suggested

Characterization of the cytochrome P-450IIC3 gene and 5' flanking region of P-450IIC1

Cytochromes P-450 are a superfamily of monooxygenases which metabolize a myriad of endogenous and exogenous substances. Cytochrome P-450 genes are differentially expressed in various tissues and differentially induced by many chemical agents. The rabbit cytochrome P-450IIC subfamily contains both phenobarbital inducible and constitutive genes. Comparative studies of the gene structures of this subfamily may shed light on the mechanism of differential induction of cytochrome P-450 genes. The purpose of this project is to characterize the cytochrome P-450IIC3 gene, which is a constitutive gene with respect to phenobarbital, and the 5\sp\prime-flanking region of the P-450IIC1 gene which is induced by phenobarbital. Two rabbit liver DNA genomic libraries were screened for the presence of the cytochrome P-450IIC3 and IIC1 genes. DNA from genomic clones C3.1, C3.2, C3.3, and C1.1 were isolated, and subcloned into phage M13 mp11 and phagemid pTZ18R for sequencing by the chain termination procedure. Exons 7, 8, and 9 of the P-450IIC3 gene were contained within genomic clone C3.1, exons 2, 3, 4, 5, and 6 were in clone C3.2, and exons 1, and 2 were in clone C3.3. Only two differences between the gene and the cDNA nucleotide sequences were observed, one of which resulted an amino acid change. The total length of the cytochrome P-450IIC3 gene is more than 25 kilobases. All the intron/exon junctions obey the GT/AG rule. The derived amino acid sequence has nine differences from the direct protein sequence of rabbit cytochrome P-450 3b of Ozols et al. All the intron positions of the rabbit P-450IIC3 and rat P-450e gene (a member of P-450IIB subfamily) are identical. This provides further evidence for divergent evolution by gene duplication within the cytochrome P-450 gene superfamily. The 5\sp\prime-flanking region and exon 1 of the P-450IIC1 gene were in clone C1.1. The intron 1 position and intron/exon junction were the same as in the P-450IIC3 gene. The 5\sp\prime-flanking regions of both P-450IIC1 and IIC3 contained TATA boxes which were about 25 bp upstream from the RNA start sites as determined by primer extension. The potential regulatory sequence modules included a CCAAT sequence and binding sites similar to the liver-specific factor HNF-1 and the general transcription factors, AP-1 and OCT.U of I OnlyETDs are only available to UIUC Users without author permissio

A Comprehensive Map of FDA-Approved Pharmaceutical Products

With the increasing research and development (R&D) difficulty of new molecular entities (NMEs), novel drug delivery systems (DDSs) are attracting widespread attention. This review investigated the current distribution of Food and Drug Administration (FDA)-approved pharmaceutical products and evaluated the technical barrier for the entry of generic drugs and highlighted the success and failure of advanced drug delivery systems. According to the ratio of generic to new drugs and the four-quadrant classification scheme for evaluating the commercialization potential of DDSs, the results showed that the traditional dosage forms (e.g., conventional tablets, capsules and injections) with a lower technology barrier were easier to reproduce, while advanced drug delivery systems (e.g., inhalations and nanomedicines) with highly technical barriers had less competition and greater market potential. Our study provides a comprehensive insight into FDA-approved products and deep analysis of the technical barriers for advanced drug delivery systems. In the future, the R&D of new molecular entities may combine advanced delivery technologies to make drug candidates into more therapeutically effective formulations

Academic Career Progression of Chinese-Origin Pharmacy Faculty Members in Western Countries

Background: The field of Pharmacy education is experiencing a paucity of underrepresented minorities (URMs) faculty worldwide. The aim of this study is to investigate the current professional status of Chinese-origin pharmacy faculty members, who are considered as a good model of URMs at pharmacy academia in western countries, and identify the influencing factors to their academic career progression in academic careers. Methods: An online questionnaire was sent to Chinese-origin academic staffs at pharmacy schools in US, UK, Canada, Australia, and New Zealand. The survey comprised demographic information, educational background, and the influencing factors to academic career progression. Results: The vast majority of Chinese faculty members who worked in US were male. Individuals with junior academic title comprised the largest proportion. Over 75% of Chinese-origin pharmacy academics were involved in scientific disciplines (e.g., pharmaceutics, pharmacology, and medicinal chemistry). Usually, Chinese-origin academic members spent 4 years obtaining their first academic jobs after finishing PhD degree, and need 5–6 years to get academic promotion. The contributing factors of academic promotion were high quality publications and external funding. Conclusion: Our research offers a deep insight into academic career progression for URMs and give some valuable advice for their pharmacy academic paths

Internationalization of traditional Chinese medicine: current international market, internationalization challenges and prospective suggestions

Abstract Through reviewing the current international market for traditional Chinese medicine (TCM), this paper identified the internationalization challenges for TCM, including unclear therapeutic material basis and mechanism, difficulty of quality control, low preparation level, registration/policy barriers, and shortage of intellectual property. To deal with these challenges, suggestions were given including: (1) product innovation of TCM (study the TCM by using the methods and means of western medicine; innovate the basic theory of TCM; develop TCM health product); (2) standard innovation of TCM; (3) building big data platform of Chinese medicine (big data platform of TCM preparation; big data platform on the quality of TCM)

PHOTOGRAMMETRIC TECHNIQUE FOR ANALYZING RAINDROP SIZE DISTRIBUTION

Rainfall erosivity and rainfall kinetic energy are predominantly affected by the rainfall droplet size distribution characteristics. This study aims to determine the raindrop size distribution with different rainfall intensities in East Malaysia using photographic method and MATLAB image processing tools. A total of five natural rainfall intensities of different ranges were analyzed: 5.51 mm hr-1 , 14.20 mm hr-1 , 28.80 mm hr-1 , 32.41 mm hr-1 and 58.11 mm hr-1 . A digital camera with fast capturing mode was used to capture falling raindrops and the droplets were then processed in MATLAB to determine the raindrop size distribution. It was found that the captured raindrop diameters were within the range of 0.1 mm and 5.0 mm, and a higher portion of the raindrops fell between 0.1 mm and 1.0 mm. The results also showed that higher rainfall intensities would promote the formation of larger raindrop sizes, i.e., from 1.0 mm to 5.0 mm, and lower rainfall intensities tended result in higher drop counts in smaller raindrop sizes of <1.0 mm. The modified image processing tools of MATLAB had proved a shorter analysis duration and higher accuracy of the raindrop size determination than the human visual system. The novelty of this study contributes to the understanding of the equatorial rainfall properties. This enhances the study of the rainfall kinetic energy and soil erosion rate estimation. The findings demonstrate the capability of photogrammetric techniques for determination of raindrop size distribution