Pancreatic cancer (PC) is among foremost causes of cancer related deaths worldwide due to generic symptoms, lack of effective screening strategies and resistance to chemo- and radiotherapies. The ...risk factors associated with PC include several metabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus (T2DM). Studies have shown that obesity and T2DM are associated with PC pathogenesis; however, their role in PC initiation and development remains obscure.
Several biochemical and physiological factors associated with obesity and/or T2DM including adipokines, inflammatory mediators, and altered microbiome are involved in PC progression and metastasis albeit by different molecular mechanisms. Deep understanding of these factors and causal relationship between factors and altered signaling pathways will facilitate deconvolution of disease complexity as well as lead to development of novel therapies. In the present review, we focuses on the interplay between adipocytokines, gut microbiota, adrenomedullin, hyaluronan, vanin and matrix metalloproteinase affected by metabolic alteration and pancreatic tumor progression.
Metabolic diseases, such as obesity and T2DM, contribute PC development through altered metabolic pathways. Delineating key players in oncogenic development in pancreas due to metabolic disorder could be a beneficial strategy to combat cancers associated with metabolic diseases in particular, PC.
Obesity is a complex condition that increases the risk of life threatening diseases such as cardiovascular disease and diabetes. Studying the gene regulation of obesity is important for understanding ...the molecular mechanisms behind the obesity derived diseases and may lead to better intervention and treatment plans. MicroRNAs (miRNAs) are short non-coding RNAs regulating target mRNA by binding to their 3'UTR. They are involved in numerous biological processes and diseases, including obesity. In this study we use a mixed breed pig model designed for obesity studies to investigate differentially expressed miRNAs in subcutaneous adipose tissue by RNA sequencing (RNAseq). Both male and female pigs are included to explore gender differences. The RNAseq study shows that the most highly expressed miRNAs are in accordance with comparable studies in pigs and humans. A total of six miRNAs are differentially expressed in subcutaneous adipose tissue between the lean and obese group of pigs, and in addition gender specific significant differential expression is observed for a number of miRNAs. The differentially expressed miRNAs have been verified using qPCR. The results of these studies in general confirm the trends found by RNAseq. Mir-9 and mir-124a are significantly differentially expressed with large fold changes in subcutaneous adipose tissue between lean and obese pigs. Mir-9 is more highly expressed in the obese pigs with a fold change of 10 and a p-value < 0.001. Mir-124a is more highly expressed in the obese pigs with a fold change of 114 and a p-value < 0.001. In addition, mir-124a is significantly higher expressed in abdominal adipose tissue in male pigs with a fold change of 119 and a p-value < 0.05. Both miRNAs are also significantly higher expressed in the liver of obese male pigs where mir-124a has a fold change of 12 and mir-9 has a fold change of 1.6, both with p-values < 0.05.
There is strong and consistent evidence that identification with social groups is an important predictor of (ill‐)health‐related outcomes. However, the mediating mechanisms of the social ...identification–health link remain unclear. We present results from two studies, which aimed to test how perceived social support and collective self‐efficacy mediate the effect of social identification on emotional exhaustion, chronic stress, and depressive symptoms. Study 1 (N = 180) employed a longitudinal two‐wave design, whereas Study 2 (N = 100) used a field‐experimental design with a manipulation of participants’ social identity. Both studies consistently show that social identification was positively related to perceived social support, which, in turn, was positively associated with collective self‐efficacy. Collective self‐efficacy, finally, was negatively related to ill‐health outcomes.
Impressive progress has been made in the course the last decades in understanding astrophysical objects. Increasing precision of nuclear physics data has contributed significantly to this success, ...but now a better understanding of several important findings is frequently limited by uncertainties related to the available nuclear physics data. Consequently it is desirable to improve significantly the quality of these data. An important step towards higher precision is an excellent signal to background ratio of the data. Placing an accelerator facility inside an underground laboratory reducing the cosmic ray induced background by six orders of magnitude is a powerful method to reach this goal, even though careful reduction of environmental and beam induced background must still be considered. Experience in the field of underground nuclear astrophysics has been gained since 20 years due to the pioneering work of the LUNA Collaboration (Laboratory for Underground Nuclear Astrophysics) operating inside the underground laboratories of the Laboratori Nazionali del Gran Sasso (LNGS) in Italy. Based on the success of this work presently also several other projects for underground laboratories dedicated to nuclear astrophysics are being pursued worldwide. This contribution will give a survey of the past experience in underground nuclear astrophysics as well as an outlook on future developments.
Radioactivity was recently discovered as a source of decoherence and correlated errors for the real-world implementation of superconducting quantum processors. In this work, we measure levels of ...radioactivity present in a typical laboratory environment (from muons, neutrons, and
γ
-rays emitted by naturally occurring radioactive isotopes) and in the most commonly used materials for the assembly and operation of state-of-the-art superconducting qubits. We present a GEANT-4 based simulation to predict the rate of impacts and the amount of energy released in a qubit chip from each of the mentioned sources. We finally propose mitigation strategies for the operation of next-generation qubits in a radio-pure environment.
Obesity and its comorbidities are an increasing challenge for both affected individuals and health care systems, worldwide. In obese individuals, perturbation of expression of both protein-coding ...genes and microRNAs (miRNA) are seen in obesity-relevant tissues (i.e. adipose tissue, liver and skeletal muscle). miRNAs are small non-coding RNA molecules which have important regulatory roles in a wide range of biological processes, including obesity. Rodents are widely used animal models for human diseases including obesity. However, not all research is applicable for human health or diseases. In contrast, pigs are emerging as an excellent animal model for obesity studies, due to their similarities in their metabolism, their digestive tract and their genetics, when compared to humans. The Göttingen minipig is a small sized easy-to-handle pig breed which has been extensively used for modeling human obesity, due to its capacity to develop severe obesity when fed ad libitum. The aim of this study was to identify differentially expressed of protein-coding genes and miRNAs in a Göttingen minipig obesity model. Liver, skeletal muscle and abdominal adipose tissue were sampled from 7 lean and 7 obese minipigs. Differential gene expression was investigated using high-throughput quantitative real-time PCR (qPCR) on 90 mRNAs and 72 miRNAs. The results revealed de-regulation of several obesity and inflammation-relevant protein-coding genes and miRNAs in all tissues examined. Many genes that are known to be de-regulated in obese humans were confirmed in the obese minipigs and several of these genes have target sites for miRNAs expressed in the opposing direction of the gene, confirming miRNA-mediated regulation in obesity. These results confirm the translational value of the pig for human obesity studies.
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