To investigate the full range of molecular changes associated with erectile dysfunction (ED) in Type 1 diabetes, we examined alterations in penile gene expression in streptozotocin-induced diabetic rats and littermate controls. With the use of Affymetrix GeneChip arrays and statistical filtering, 529 genes/transcripts were considered to be differentially expressed in the diabetic rat cavernosum compared with control. Gene Ontology (GO) classification indicated that there was a decrease in numerous extracellular matrix genes (e.g., collagen and elastin related) and an increase in oxidative stress-associated genes in the diabetic rat cavernosum. In addition, PubMatrix literature mining identified differentially expressed genes previously shown to mediate vascular dysfunction [e.g., ceruloplasmin (Cp), lipoprotein lipase, and Cd36] as well as genes involved in the modulation of the smooth muscle phenotype (e.g., Kruppel-like factor 5 and chemokine C-X3-C motif ligand 1). Real-time PCR was used to confirm changes in expression for 23 relevant genes. Further validation of Cp expression in the diabetic rat cavernosum demonstrated increased mRNA levels of the secreted and anchored splice variants of Cp. CP protein levels showed a 1.9-fold increase in tissues from diabetic rats versus controls. Immunohistochemistry demonstrated localization of CP protein in cavernosal sinusoids of control and diabetic animals, including endothelial and smooth muscle layers. Overall, this study broadens the scope of candidate genes and pathways that may be relevant to the pathophysiology of diabetes-induced ED as well as highlights the potential complexity of this disorder.
The Set4 protein in the yeast contains both a PHD finger and a SET domain, a common signature of chromatin-associated proteins, and shares sequence homology with the yeast protein Set3, the fly protein UpSET, and the human protein mixed-lineage leukemia 5 (MLL5). However, the biological role for Set4 and its potential function in chromatin regulation has not been well defined. Here, we analyzed yeast cell phenotypes associated with loss of Set4 or its overexpression, which revealed that Set4 protects against oxidative stress induced by hydrogen peroxide. Gene expression analysis indicated that Set4 promotes the activation of stress response genes in the presence of oxidative insults. Using ChIP analysis and other biochemical assays, we also found that Set4 interacts with chromatin and directly localizes to stress response genes upon oxidative stress. However, recombinant Set4 did not show detectable methyltransferase activity on histones. Our findings also suggest that Set4 abundance in the cell is balanced under normal and stress conditions to promote survival. Overall, these results suggest a model in which Set4 is a stress-responsive, chromatin-associated protein that activates gene expression programs required for cellular protection against oxidative stress. This work advances our understanding of mechanisms that protect cells during oxidative stress and further defines the role of the Set3-Set4 subfamily of SET domain-containing proteins in controlling gene expression in response to adverse environmental conditions.
The internal anal sphincter is easily damaged with the use of the Parks' anal retractor. When possible, its use should be avoided to obtain better manometric and functional results.
Sacroiliac (SI) joint pathology is a newly appreciated contributor to lower back pain. Sacroiliac joint fusion (SIJF) has grown rapidly in popularity in association with the advent of minimally-invasive surgical techniques. This has led to an explosion of new medical devices used for SIJF. The objective of this article is to outline clinical trends, summarize the current data, and categorize novel devices for SIJF. Trends in SI joint pathology and fusion were obtained via the Healthcare Cost and Utilization Project's (HCUP) National Inpatient Sample (NIS) database and Web of Science. To review literature on devices for SIJF, PubMed was searched using the Boolean phrase "sacroiliac joint AND (fusion OR arthrodesis)" since 2010. To establish a list of SIJF devices not represented in the literature, searches were performed on the FDA 510(k), premarket approval, and de novo databases, as well as Google and LinkedIn. Literature review yielded 11 FDA-approved devices for minimally invasive SIJF. Database query yielded an additional 22 devices for a total of 33 devices. Twenty-one devices used the lateral transiliac approach, six posterior allograft approach, three posterolateral approach, and three combined the lateral transiliac and posterolateral approaches. The evidence for the lateral transiliac approach is the most robust. Many novel devices have been developed for minimally invasive SIJF over the past 10 years. Further randomized comparative trials are warranted to evaluate different surgical approaches and novel devices at this time.
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