Fatty Acid-Induced Lipotoxicity in Pancreatic Beta-Cells During Development of Type 2 Diabetes

Type 2 diabetes is caused by chronic insulin resistance and progressive decline in beta-cell function. Optimal beta-cell function and mass is essential for glucose homeostasis and beta-cell impairment leads to the development of diabetes. Elevated levels of circulating fatty acids (FAs) and disturbances in lipid metabolism regulation are associated with obesity, and they are major factors influencing the increase in the incidence of type 2 diabetes. Chronic free FA (FFA) treatment induces insulin resistance and beta-cell dysfunction; therefore, reduction of elevated plasma FFA levels might be an important therapeutic target in obesity and type 2 diabetes. Lipid signals via receptors, and intracellular mechanisms are involved in FFA-induced apoptosis. In this paper, we discuss lipid actions in beta cells, including effects on metabolic pathways and stress responses, to help further understand the molecular mechanisms of lipotoxicity-induced type 2 diabetes

PwRn1, a novel Ty3/gypsy-like retrotransposon of Paragonimus westermani: molecular characters and its differentially preserved mobile potential according to host chromosomal polyploidy

<p>Abstract</p> <p>Background</p> <p>Retrotransposons have been known to involve in the remodeling and evolution of host genome. These reverse transcribing elements, which show a complex evolutionary pathway with diverse intermediate forms, have been comprehensively analyzed from a wide range of host genomes, while the information remains limited to only a few species in the phylum Platyhelminthes.</p> <p>Results</p> <p>A LTR retrotransposon and its homologs with a strong phylogenetic affinity toward <it>CsRn1 </it>of <it>Clonorchis sinensis </it>were isolated from a trematode parasite <it>Paragonimus westermani </it>via a degenerate PCR method and from an insect species <it>Anopheles gambiae </it>by <it>in silico </it>analysis of the whole mosquito genome, respectively. These elements, designated <it>PwRn1 </it>and <it>AgCR-1 </it>– <it>AgCR-14 </it>conserved unique features including a t-RNA^Trpprimer binding site and the unusual CHCC signature of Gag proteins. Their flanking LTRs displayed >97% nucleotide identities and thus, these elements were likely to have expanded recently in the trematode and insect genomes. They evolved heterogeneous expression strategies: a single fused ORF, two separate ORFs with an identical reading frame and two ORFs overlapped by -1 frameshifting. Phylogenetic analyses suggested that the elements with the separate ORFs had evolved from an ancestral form(s) with the overlapped ORFs. The mobile potential of <it>PwRn1 </it>was likely to be maintained differentially in association with the karyotype of host genomes, as was examined by the presence/absence of intergenomic polymorphism and mRNA transcripts.</p> <p>Conclusion</p> <p>Our results on the structural diversity of <it>CsRn1</it>-like elements can provide a molecular tool to dissect a more detailed evolutionary episode of LTR retrotransposons. The <it>PwRn1</it>-associated genomic polymorphism, which is substantial in diploids, will also be informative in addressing genomic diversification following inter-/intra-specific hybridization in <it>P. westermani </it>populations.</p

Phlegmonous Enteritis in a Patient with Congestive Heart Failure and Colon Cancer

Phlegmonous enteritis is a rare infective inflammatory disease of the intestine, predominantly involving the submucosal layer. It is difficult to diagnose and often fatal. Its association with alcoholism and various liver diseases, although rarely reported, is well documented. We report a case of phlegmonous enteritis in a male patient with congestive heart failure and colon cancer, and describe the ultrasonographic and CT findings

Therapeutic genome editing for Charcot-marie-tooth disease type 1a

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted regulatory region of human PMP22 to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multi copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a potential therapeutic efficacy of CRISPR/Cas9-mediated targeting of regulatory region of PMP22 to treat CMT1A. Please click Additional Files below to see the full abstract

A Case of Disseminated and Fulminant Plasmacytomas That Developed during Bortezomib Treatment

Multiple myeloma is an incurable and slow growing plasma cell neoplasm. The introduction of new drugs has increased the number of treatment options. Bortezomib, the first-in-class proteasome inhibitor, has been shown to have a significant antitumor activity in the treatment of relapse/refractory patients with multiple myeloma. Additionally, plasmacytomas have shown significant response to bortezomib. In this case report, we describe a patient who developed disseminated and fulminant extramedullary plasmacytomas during combination chemotherapy treatment with bortezomib within a short period, after having shown clinical improvement

Vaccination and Complementary and Alternative Medicine in Patients with Inflammatory Bowel Disease

Background/AimsVaccinations in patients with inflammatory bowel disease (IBD) are recommended to prevent infectious diseases. However, there are few reports of vaccination in IBD patients in Korea. The frequency of complementary and alternative medicine (CAM) use is high despite its uncertain effectiveness. This study aimed to identify the rates of vaccination and use of CAM in patients with IBD.MethodsA total of 219 patients attended an education session for IBD patients held at Severance Hospital on March 23, 2013. We conducted a survey on vaccination and CAM use in IBD patients; 120 patients completed the questionnaire.ResultsThe influenza vaccination rate was 44.2% and pneumococcal vaccination rate was 4.2%. Thirty-one (66%) patients were aware of the importance of vaccination. The vaccination rate was higher in patients who were aware of the importance of vaccination compared with that in patients who were unaware of the importance of vaccination (70.1% vs. 41.7%, P=0.004). The rate of CAM use was 30.0%. The most commonly used CAMs were oral products: vitamins (33.3%), red ginseng (25.0%), and probiotics (19.4%).ConclusionsAwareness of the importance of vaccination and actual vaccination rates were low in IBD patients. Despite insufficient evidence on the effectiveness of CAMs in IBD patients, many patients used CAMs. We believe that repeated education and promotion of vaccination are important. Further large-scale studies to investigate the efficacy and safety of CAMs are warranted in patients with IBD