Growth Factors Regulate Expression of Osteoblast‐Associated Genes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141995/1/jper1345.pd

Management of Hepatic Angiomyolipoma

Preoperative diagnosis of hepatic angiomyolipoma is difficult, and the treatment for it remains controversial. The aim of this study is to review our experience in the treatment of hepatic angiomyolipoma and to propose a treatment strategy for this disease. We retrospectively collected the clinical, imaging, and pathological features of patients with hepatic angiomyolipoma. Immunohistochemical studies with antibodies for HMB-45, actin, S-100, cytokeratin, vimentin, and c-kit were performed. Treatment experience and long-term follow-up results are summarized. During a period of 9 years, 10 patients with hepatic angiomyolipoma were treated at our hospital. There was marked female predominance (nine patients). Nine patients received surgical resection without complications. One patient received nonoperative management with biopsy and follow-up. One patient died 11 months after surgery because of recurrent disease. We propose all symptomatic patients should receive surgical resection for hepatic angiomyolipoma. Conservative management with close follow-up is suggested in patients with asymptomatic tumors and meet the following criteria: (1) tumor size smaller than 5 cm, (2) angiomyolipoma proved through fine needle aspiration biopsy, (3) patients with good compliance, and (4) not a hepatitis virus carrier

Association between plasma metabolites and gene expression profiles in five porcine endocrine tissues

Background: Endocrine tissues play a fundamental role in maintaining homeostasis of plasma metabolites such as non-esterified fatty acids and glucose, the levels of which reflect the energy balance or the health status of animals. However, the relationship between the transcriptome of endocrine tissues and plasma metabolites has been poorly studied. Methods: We determined the blood levels of 12 plasma metabolites in 27 pigs belonging to five breeds, each breed consisting of both females and males. The transcriptome of five endocrine tissues i.e. hypothalamus, adenohypophysis, thyroid gland, gonads and backfat tissues from 16 out of the 27 pigs was also determined. Sex and breed effects on the 12 plasma metabolites were investigated and associations between genes expressed in the five endocrine tissues and the 12 plasma metabolites measured were analyzed. A probeset was defined as a quantitative trait transcript (QTT) when its association with a particular metabolic trait achieved a nominal P value < 0.01. Results: A larger than expected number of QTT was found for non-esterified fatty acids and alanine aminotransferase in at least two tissues. The associations were highly tissue-specific. The QTT within the tissues were divided into co-expression network modules enriched for genes in Kyoto Encyclopedia of Genes and Genomes or gene ontology categories that are related to the physiological functions of the corresponding tissues. We also explored a multi-tissue co-expression network using QTT for non-esterified fatty acids from the five tissues and found that a module, enriched in hypothalamus QTT, was positioned at the centre of the entire multi-tissue network. Conclusions: These results emphasize the relationships between endocrine tissues and plasma metabolites in terms of gene expression. Highly tissue-specific association patterns suggest that candidate genes or gene pathways should be investigated in the context of specific tissues

Lrp Acts as Both a Positive and Negative Regulator for Type 1 Fimbriae Production in Salmonella enterica Serovar Typhimurium

Leucine-responsive regulatory protein (Lrp) is known to be an indirect activator of type 1 fimbriae synthesis in Salmonella enterica serovar Typhimurium via direct regulation of FimZ, a direct positive regulator for type 1 fimbriae production. Using RT-PCR, we have shown previously that fimA transcription is dramatically impaired in both lrp-deletion (Δlrp) and constitutive-lrp expression (lrpC) mutant strains. In this work, we used chromosomal PfimA-lacZ fusions and yeast agglutination assays to confirm and extend our previous results. Direct binding of Lrp to PfimA was shown by an electrophoretic mobility shift assay (EMSA) and DNA footprinting assay. Site-directed mutagenesis revealed that the Lrp-binding motifs in PfimA play a role in both activation and repression of type 1 fimbriae production. Overproduction of Lrp also abrogates fimZ expression. EMSA data showed that Lrp and FimZ proteins independently bind to PfimA without competitive exclusion. In addition, both Lrp and FimZ binding to PfimA caused a hyper retardation (supershift) of the DNA-protein complex compared to the shift when each protein was present alone. Nutrition-dependent cellular Lrp levels closely correlated with the amount of type 1 fimbriae production. These observations suggest that Lrp plays important roles in type 1 fimbriation by acting as both a positive and negative regulator and its effect depends, at least in part, on the cellular concentration of Lrp in response to the nutritional environment

Synthetic human cell fate regulation by protein-driven RNA switches

Understanding how to control cell fate is crucial in biology, medical science and engineering. In this study, we introduce a method that uses an intracellular protein as a trigger for regulating human cell fate. The ON/OFF translational switches, composed of an intracellular protein L7Ae and its binding RNA motif, regulate the expression of a desired target protein and control two distinct apoptosis pathways in target human cells. Combined use of the switches demonstrates that a specific protein can simultaneously repress and activate the translation of two different mRNAs: one protein achieves both up- and downregulation of two different proteins/pathways. A genome-encoded protein fused to L7Ae controlled apoptosis in both directions (death or survival) depending on its cellular expression. The method has potential for curing cellular defects or improving the intracellular production of useful molecules by bypassing or rewiring intrinsic signal networks

InterPro in 2017-beyond protein family and domain annotations

InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder. These developments enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences

Advances in the field of nanooncology

Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important chapter of nanomedicine. Nanobiotechnology has refined and extended the limits of molecular diagnosis of cancer, for example, through the use of gold nanoparticles and quantum dots. Nanobiotechnology has also improved the discovery of cancer biomarkers, one such example being the sensitive detection of multiple protein biomarkers by nanobiosensors. Magnetic nanoparticles can capture circulating tumor cells in the bloodstream followed by rapid photoacoustic detection. Nanoparticles enable targeted drug delivery in cancer that increases efficacy and decreases adverse effects through reducing the dosage of anticancer drugs administered. Nanoparticulate anticancer drugs can cross some of the biological barriers and achieve therapeutic concentrations in tumor and spare the surrounding normal tissues from toxic effects. Nanoparticle constructs facilitate the delivery of various forms of energy for noninvasive thermal destruction of surgically inaccessible malignant tumors. Nanoparticle-based optical imaging of tumors as well as contrast agents to enhance detection of tumors by magnetic resonance imaging can be combined with delivery of therapeutic agents for cancer. Monoclonal antibody nanoparticle complexes are under investigation for diagnosis as well as targeted delivery of cancer therapy. Nanoparticle-based chemotherapeutic agents are already on the market, and several are in clinical trials. Personalization of cancer therapies is based on a better understanding of the disease at the molecular level, which is facilitated by nanobiotechnology. Nanobiotechnology will facilitate the combination of diagnostics with therapeutics, which is an important feature of a personalized medicine approach to cancer

Androgen receptor expression predicts breast cancer survival: the role of genetic and epigenetic events

Background: Breast cancer outcome, including response to therapy, risk of metastasis and survival, is difficult to predict using currently available methods, highlighting the urgent need for more informative biomarkers. Androgen receptor (AR) has been implicated in breast carcinogenesis however its potential to be an informative biomarker has yet to be fully explored. In this study, AR protein levels were determined in a cohort of 73 Grade III invasive breast ductal adenocarcinomas

Antioxidant intervention of smoking-induced lung tumor in mice by vitamin E and quercetin

<p>Abstract</p> <p>Background</p> <p>Epidemiological and in vitro studies suggest that antioxidants such as quercetin and vitamin E (VE) can prevent lung tumor caused by smoking; however, there is limited evidence from animal studies.</p> <p>Methods</p> <p>In the present study, Swiss mouse was used to examine the potential of quercetin and VE for prevention lung tumor induced by smoking.</p> <p>Results</p> <p>Our results suggest that the incidence of lung tumor and tumor multiplicity were 43.5% and 1.00 ± 0.29 in smoking group; Quercetin has limited effects on lung tumor prevention in this in vivo model, as measured by assays for free radical scavenging, reduction of smoke-induced DNA damage and inhibition of apoptosis. On the other hand, vitamin E drastically decreased the incidence of lung tumor and tumor multiplicity which were 17.0% and 0.32 ± 0.16, respectively (p < 0.05); and demonstrated prominent antioxidant effects, reduction of DNA damage and decreased cell apoptosis (p < 0.05). Combined treatment with quercetin and VE in this animal model did not demonstrate any effect greater than that due to vitamin E alone. In addition, gender differences in the occurrence of smoke induced-lung tumor and antioxidant intervention were also observed.</p> <p>Conclusion</p> <p>We conclude that VE might prevent lung tumor induced by smoking in Swiss mice.</p