The prevalence of depression and anxiety in seafarers type 2 diabetic patients

Depression and anxiety are co-morbid condition in diabetes as disease-related psychological reactions on this chronic metabolic illness. This study was aimed to determine the occurrence of depression and anxiety in seafarer's type 2 diabetic patients. A random sample of 52 diabetic seafarers treated with diet and oral glucose lowering agents, and 56 healthy seafarers were screened for depression with The Beck Depression Inventory (BDI) and for anxiety with State-Trait Anxiety Inventory (STAI 1, STAI 2). Depression (BDI > 18.5) and anxiety (STAI < 28.5) was significantly higher in the group of diabetic seafarers than in control group (more than 30%). Significant correlation was noted between depression and duration of diabetes mellitus, degree of obesity and poor glycaemic control (HbA1C > 8%) and longer duration of shipping routes (over 6 months). The proportion of depression and anxiety was found higher in seafarer's type 2 diabetic patients than in the healthy seafarers.     

Analgesic effect of high intensity laser therapy in knee osteoarthritis

Knee osteoarthritis (KOA), the most common type of osteoarthritis (OA), is associated with pain and inflammation of the joint capsule, impaired muscular stabilization, reduced range of motion and functional disability. High-intensity laser therapy (HILT) involves higher-intensity laser radiation and causes minor and slow light absorption by chromophores. Light stimulation of the deep structures, due to high intensity laser therapy, activates cell metabolism through photochemical effect. The transmissions of pain stimulus are slowed down and result in a quick achievement of pain relief. The aim of our research was to investigate the prompt analgesic effect of HILT on patients with KOA. Knee radiographs were performed on all patients and consequently graded using the Kellgren-Lawrence grading scale (K/L). A group of 96 patients (75 female, 21 male, mean age 59.2) with K/L 2 and 3 were submitted to HILT therapy. Pain intensity was evaluated with visual analogue scale (VAS) before and after the treatment. HILT consisted in one daily application, over a period of ten days, using protocol wavelength, frequency and duration. The results showed statistically significant decrease in VAS after the treatment (p < 0.001). Considering these results, HILT enables prompt analgesic effects in KOA treatment. Therefore HILT is a reliable option in KOA physical therapy.     

The what, where, how and why of gene ontology--a primer for bioinformaticians

With high-throughput technologies providing vast amounts of data, it has become more important to provide systematic, quality annotations. The Gene Ontology (GO) project is the largest resource for cataloguing gene function. Nonetheless, its use is not yet ubiquitous and is still fraught with pitfalls. In this review, we provide a short primer to the GO for bioinformaticians. We summarize important aspects of the structure of the ontology, describe sources and types of functional annotations, survey measures of GO annotation similarity, review typical uses of GO and discuss other important considerations pertaining to the use of GO in bioinformatics applications.     

Design, Synthesis, and Biological Evaluation of Novel cRGD-Paclitaxel Conjugates for Integrin-Assisted Drug Delivery

The efficacy of taxane-based antitumor therapy is limited by several drawbacks which result in a poor therapeutic index. Thus, the development of approaches that favor selective delivery of taxane drugs (e.g., paclitaxel, PTX) to the disease area represents a truly challenging goal. On the basis of the strategic role of integrins in tumor cell survival and tumor progression, as well as on integrin expression in tumors, novel molecular conjugates were prepared where PTX is covalently attached to either cyclic AbaRGD (Azabicycloalkane-RGD) or AmproRGD (Aminoproline-RGD) integrin-recognizing matrices via structurally diverse connections. Receptor-binding assays indicated satisfactory-to-excellent α(V)β(3) binding capabilities for most conjugates, while in vitro growth inhibition assays on a panel of human tumor cell lines revealed outstanding cell sensitivity values. Among the nine conjugate ensemble, derivative 21, bearing a robust triazole ring connected to ethylene glycol units by an amide function and showing excellent cell sensitivity properties, was selected for in vivo studies in an ovarian carcinoma model xenografted in immunodeficient mice. Remarkable antitumor activity was attained, superior to that of PTX itself, which was associated with a marked induction of aberrant mitoses, consistent with the mechanism of action of spindle poisons. Overall, the novel cRGD-PTX conjugates disclosed here represent promising candidates for further advancement in the domain of targeted antitumor therapy.     

Different Roles for Lactococcal Aggregation Factor and Mucin Binding Protein in Adhesion to Gastrointestinal Mucosa

Adhesion of bacteria to mucosal surfaces and epithelial cells is one of the key features for the selection of probiotics. In this study, we assessed the adhesion property of Lactococcus lactis subsp. lactis BGKP1 based on its strong autoaggregation phenotype and the presence of the mucin binding protein (MbpL). Genes involved in aggregation (aggL) and possible interaction with mucin (mbpL), present on the same plasmid pKP1, were previously separately cloned in the plasmid pAZIL. In vivo and in vitro experiments revealed potentially different physiological roles of these two proteins in the process of adherence to the intestine during the passage of the strain through the gastrointestinal tract. We correlated the in vitro and in vivo aggregation of the BGKP1-20 carrying plasmid with aggL to binding to the colonic mucus through nonspecific hydrophobic interactions. The expression of AggL on the bacterial cell surface significantly increased the hydrophobicity of the strain. On the other hand, the presence of AggL in the strain reduced its ability to adhere to the ileum. Moreover, MbpL protein showed an affinity to bind gastric type mucin proteins such as MUC5AC. This protein did not contribute to the binding of the strain to the ileal or colonic part of the intestine. Different potential functions of lactococcal AggL and MbpL proteins in the process of adhesion to the gastrointestinal tract are proposed.     

Recruitment of the RNA helicase RHAU to stress granules via a unique RNA-binding domain

In response to environmental stress, the translation machinery of cells is reprogrammed. The majority of actively translated mRNAs are released from polysomes and driven to specific cytoplasmic foci called stress granules (SGs) where dynamic changes in protein-RNA interaction determine the subsequent fate of mRNAs. Here we show that the DEAH box RNA helicase RHAU is a novel SG-associated protein. Although RHAU protein was originally identified as an AU-rich element-associated protein involved in urokinase-type plasminogen activator mRNA decay, it was not clear whether RHAU could directly interact with RNA. We have demonstrated that RHAU physically interacts with RNA in vitro and in vivo through a newly identified N-terminal RNA-binding domain, which was found to be both essential and sufficient for RHAU localization in SGs. We have also shown that the ATPase activity of RHAU plays a role in the RNA interaction and in the regulation of protein retention in SGs. Thus, our results show that RHAU is the fourth RNA helicase detected in SGs, after rck/p54, DDX3, and eIF4A, and that its association with SGs is dynamic and mediated by an RHAU-specific RNA-binding domain.     

Defining targets of modulation of human tumor cell response to cisplatin

We previously observed that in yeast cisplatin activates different pathways accounting for stress response. Here, we investigated whether genes involved in yeast drug response were modulated by cisplatin in human tumor cell lines (A2780, IGROV-1, A431, U2-OS) including cisplatin-resistant sublines (A2780/BBR, IGROV-1/Pt1, A431/Pt and U2-OS/Pt). Factors and pathways involved in stress response (glutathione-S-transferase, proteasome, checkpoint control and recombinational repair) were increased by cisplatin in human tumor sensitive and resistant cells. Moreover, sensitization to cisplatin by pharmacologically targeting glutathione or proteasome was observed in sensitive and resistant cells. Interestingly, only in IGROV-1/Pt1 cells, in which cisplatin up-regulated HSP70 and HSP90, targeting of HSP90 resulted in sensitization of resistant cells, suggesting a protective role of stress response. In conclusion, the present findings support the potential relevance of interfering with heat shock protein response to increase cisplatin cytotoxicity in resistant cells. Overall, pathways activated by cisplatin in human tumor cells appear cell-type specific, at least in part reflecting the stress response observed in yeast.     

Molecular analysis of human Siglec-8 orthologs relevant to mouse eosinophils: identification of mouse orthologs of Siglec-5 (mSiglec-F) and Siglec-10 (mSiglec-G)

We recently identified a novel human sialic acid binding immunoglobulin-like lectin, Siglec-8, using mRNA from human eosinophils. To search for a mouse Siglec (mSiglec) ortholog of Siglec-8 and other mouse Siglec paralogs, we conducted public database searches with cDNA sequences of human Siglec-5 to -10 and identified two novel mSiglecs. One has significant sequence identity to human Siglec-5 and is a splice variant of mSiglec-F. The other has greatest sequence identity to human Siglec-10 (mSiglec-G). Both mSiglecs have extracellular Ig-like domains and intracellular tyrosine-based motifs. To determine whether these mSiglecs were relevant to mouse eosinophils, RT-PCR and Northern blot analysis were performed. We detected expression of mSiglec-5 (or -F), -10, and -E mRNA in purified mouse eosinophils, but Northern blot data comparing expression in tissues from normal, IL-5 transgenic, and allergen-sensitized and -challenged mice suggest that mSiglec-10 is probably most relevant to mouse eosinophils.     

The Bloom's syndrome helicase interacts directly with the human DNA mismatch repair protein hMSH6

Bloom's syndrome (BS) is a rare genetic disorder characterised by genome instability and cancer susceptibility. BLM, the BS gene product, belongs to the highly-conserved RecQ family of DNA helicases. Although the exact function of BLM in human cells remains to be defined, it seems likely that BLM eliminates some form of homologous recombination (HR) intermediate that arises during DNA replication. Similarly, the mismatch repair (MMR) system also plays a crucial role in the maintenance of genomic stability, by correcting DNA errors generated during DNA replication. Recent evidence implicates components of the MMR system also in HR repair. We now show that hMSH6, a component of the heterodimeric mismatch recognition complex hMSH2/hMSH6 (hMutS(alpha)), interacts with the BLM protein both in vivo and in vitro. In agreement with these findings, BLM and hMSH6 co-localise to discrete nuclear foci following exposure of the cells to ionising radiation. However, the purified recombinant MutS(alpha) complex does not affect the helicase activity of BLM in vitro. As BLM has previously been shown to interact with the hMLH1 component of the hMLH1/hPMS2 (hMutL(alpha)) heterodimeric MMR complex, our present findings further strengthen the link between BLM and processes involving correction of DNA mismatches, such as in the regulation of the fidelity of homologous recombination events.     

Tumor suppressor gene E-cadherin and its role in normal and malignant cells

E-cadherin tumor suppressor genes are particularly active area of research in development and tumorigenesis. The calcium-dependent interactions among E-cadherin molecules are critical for the formation and maintenance of adherent junctions in areas of epithelial cell-cell contact. Loss of E-cadherin-mediated-adhesion characterises the transition from benign lesions to invasive, metastatic cancer. Nevertheless, there is evidence that E-cadherins may also play a role in the wnt signal transduction pathway, together with other key molecules involved in it, such as beta-catenins and adenomatous poliposis coli gene products.