The potential therapeutic use of renin-angiotensin system inhibitors in the treatment of inflammatory diseases

Inflammation is a normal part of the immune response to injury or infection but its dysregulation promotes the development of inflammatory diseases, which cause considerable human suffering. Non-steroidal anti-inflammatory agents (NSAIDs) are the most commonly prescribed agents for the treatment of inflammatory diseases but they are accompanied by a broad range of side effects, including gastrointestinal and cardiovascular events. The renin-angiotensin system (RAS) is traditionally known for its role in blood pressure regulation. However, there is increasing evidence that RAS signalling is also involved in the inflammatory response associated with several disease states. Angiotensin II increases blood pressure by binding to angiotensin type 1 (AT1) receptor, and direct renin inhibitors (DRIs), angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockers (ARBs) are clinically used as anti-hypertensive agents. Recent data suggest that these drugs also have anti-inflammatory effects. Therefore, this review summarizes these recent findings for the efficacy of two of the most widely used antihypertensive drug classes, ACE inhibitors and ARBs, to reduce or treat inflammatory diseases such as atherosclerosis, arthritis, steatohepatitis, colitis, pancreatitis and nephritis

Pharmacogenetics of anticancer drug sensitivity and toxicity in colorectal cancer

Inter-individual differences in drug response are an important cause of failure in anticancer treatment and adverse drug events in cancer patients. Gene polymorphisms related to these outcomes have been investigated in an effort to find new genetic biomarkers to predict toxicity and response to anticancer drugs. Evaluating the value single nucleotide polymorphisms (SNPs) in the genes involved in transportation, activation and metabolism of anticancer drugs provides a promising approach to select the appropriate therapeutic regimes with at least adverse reactions. This review summarizes the current knowledge about the relationship between of SNPs involved in the transportation, activation and metabolism of anticancer drugs and treatment outcomes in colorectal cancer (CRC) patients

The clinical impact of exosomes in cardiovascular disorders: from basic science to clinical application

Cardiovascular disease (CVD) is the major cause of death globally; therefore, there is a need for the identification of valid biomarker that accurately predict the risk of developing cardiovascular disease, and novel therapeutic approaches for its treatment. Exosomes are very small extracellular vesicles containing protein, lipid, transcription factors, mRNAs, non-coding RNA and nucleic acid contents, that are important players in intercellular communication, and that act via long-range signals or cell-to-cell contact. The discovery of exosomes provides potential strategies for the diagnosis and treatment of cardiovascular disease. In the current review, we have explored the potential impact of exosomes on cardiovascular physiology, and their therapeutic potential in cardiovascular disorders with a emphasize on the existing preclinical studies

Inhibition of microRNA-21 via locked nucleic acid-anti-miR suppressed metastatic features of colorectal cancer cells through modulation of programmed cell death 4.

Colorectal cancer is among the most lethal of malignancies, due to its propensity to metastatic spread and multifactorial-chemoresistance. The latter property supports the need to identify novel therapeutic approaches for the treatment of colorectal cancer. MicroRNAs are endogenous non-coding small RNA molecules that function as post-transcriptional regulators of gene expression. Recently, programmed cell death 4 has been identified as a protein that increases during apoptosis. This gene is among the potential targets of miR-21 (OncomiR). Locked nucleic acid-modified oligonucleotides have recently emerged as a potential therapeutic option for targeting microRNAs. The aim of this study was to explore the functional role of locked nucleic acid-anti-miR-21 in the LS174T cell line in vitro and in vivo models. LS174T cells were treated with locked nucleic acid-anti-miR-21 for 24, 48, and 72 h in vitro. The expression of miR-21 and PDCD4 at messenger RNA (mRNA) level was evaluated by quantitative real-time polymerase chain reaction, while the protein level of PDCD4 was determined by Western blotting. Cell migratory behavior and the cluster-forming ability of cells were assessed before and after therapy. The disseminated tumor cells were assessed in the chick chorioallantoic membrane model by Alu quantitative polymerase chain reaction. Locked nucleic acid-anti-miR-21 was transfected successfully into the LS174T cells and inhibited the expression of miR-21. Locked nucleic acid-anti-miR-21 inhibited the migration and the number of cells forming clusters. Moreover, we found that locked nucleic acid-anti-miR-21 transfection was associated with a significant reduction in metastatic properties as assessed by the in ovo model. Our findings demonstrated the novel therapeutic potential of locked nucleic acid-anti-miR-21 in colon adenocarcinoma with high miR-21 expression

CYB5A (Cytochrome B5 Type A (microsomal))

Review on Cytochrome B5 Type A, with data on DNA/RNA, on the protein encoded and the diseases in which the gene has been implicated

A New Oxadiazole-Based Topsentin Derivative Modulates Cyclin-Dependent Kinase 1 Expression and Exerts Cytotoxic Effects on Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal form of cancer characterized by drug resistance, urging new therapeutic strategies. In recent years, protein kinases have emerged as promising pharmacological targets for the treatment of several solid and hematological tumors. Interestingly, cyclin-dependent kinase 1 (CDK1) is overexpressed in PDAC tissues and has been correlated to the aggressive nature of these tumors because of its key role in cell cycle progression and resistance to the induction of apoptosis. For these reasons, CDK1 is one of the main causes of chemoresistance, representing a promising pharmacological target. In this study, we report the synthesis of new 1,2,4-oxadiazole compounds and evaluate their ability to inhibit the cell growth of PATU-T, Hs766T, and HPAF-II cell lines and a primary PDAC cell culture (PDAC3). Compound 6b was the most active compound, with IC50 values ranging from 5.7 to 10.7 M. Molecular docking of 6b into the active site of CDK1 showed the ability of the compound to interact effectively with the adenosine triphosphate binding pocket. Therefore, we assessed its ability to induce apoptosis (which increased 1.5- and 2-fold in PATU-T and PDAC3 cells, respectively) and to inhibit CDK1 expression, which was reduced to 45% in Hs766T. Lastly, compound 6b passed the ADME prediction, showing good pharmacokinetic parameters. These data demonstrate that 6b displays cytotoxic activity, induces apoptosis, and targets CDK1, supporting further studies for the development of similar compounds against PDAC

Role of regulatory miRNAs of the PI3K/AKT signaling pathway in the pathogenesis of breast cancer

Breast cancer is one of the most common tumors in women. Current data indicate that the overexpression of some microRNAs (miRNAs) is associated with breast cancer, in relation to stage, tumor size and potential for metastasis. Some studies have reported that miRNAs have critical roles in cellular processes implicated in breast cancer cell growth, migration and metastasis by targeting the PI3K/AKT oncogenic signaling pathway. Therefore, identifying novel regulatory miRNAs for this oncogenic pathway and discovery of their related target genes may represent a promising therapeutic approach for breast cancer therapy. This review highlights the recent findings about the potential role of PI3K/AKT signaling regulatory miRNAs in breast cancer tumorigenesis

The impact of statin therapy on the survival of patients with gastrointestinal cancer

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that may play an important role in the evolution of cancers, due to their effects on cancer cell metabolism. Statins effect several potential pathways, including: cell proliferation, angiogenesis, apoptosis and metastasis. The number of trials assessing the putative clinical benefits of statins in cancer is increasing. Currently, there are several trials listed on the global trial identifier website clinicaltrials.gov. Given the compelling evidence from these trials in a variety of clinical settings, there have been calls for a clinical trial of statins in the adjuvant gastrointestinal cancer setting. However, randomized controlled trials on specific cancer types in relation to statin use, as well as studies on populations without a clinical indication for using statins, have elucidated some potential underlying biological mechanisms, and the investigation of different statins is probably warranted. It would be useful for these trials to incorporate the assessment of tumour biomarkers predictive of statin response in their design. This review summarizes the recent preclinical and clinical studies that assess the application of statins in the treatment of gastrointestinal cancers with particular emphasize on their association with cancer risk

Anemia is associated with cognitive impairment in adolescent girls: a cross-sectional survey

Anemia is associated with impairment in oxygen transport, affecting an individual’s physical and mental wellbeing, and work performance. The aim of this study was to examine the prevalence of anemia and its possible association with serum antibody titers to Hsp27 (as an indicator of cellular stress), cognitive function, measures of emotion, sleep patterns in adolescent girls. A total of 940 adolescent girls were assessed to evaluate neuropsychological function with validated questionnaires. A complete blood count was determined as part of the assessment of hematological parameters. Serum anti-Hsp27 was measured for each subject. Among the total of 940 participants, 99 girls (10.5%) were anemic [hemoglobin <12(g/dl)]. Serum anti-HSP27 was significantly higher in anemic compared to healthy girls (p<0.05). There was no significant differences in depression, aggression, insomnia, daytime sleepiness and sleep apnea score between two groups. However, the total cognitive abilities score was significantly lower in the anemic girls (76.8±2.1 versus 85.7±2.5, p = 0.002). Logistic regression analysis showed that anemic girls were 1.73 times more likely than non-anemic girls to have cognitive impairment (95% confidence interval [CI] = 1.07-2.78; P = 0.025). Anemia was associated with elevated levels of anti-HSP27 and supports the hypothesis that cellular stress may be associated with anemia. Anemia was adversely associated with an assessment of cognitive abilities and was an independent risk factor for cognitive impairment in this grou

Neuropsychological function in relation to dysmenorrhea in adolescents

Objective: Hormonal variations during the menstrual cycle may affect emotional regulation. We aimed to investigate the association between dysmenorrhea (the severe abdominal pain and cramps associated with menstruation) and cognitive abilities, emotional function and sleep patterns in adolescent girls. Moreover, we evaluated the frequency of premenstrual syndrome (PMS) in our population and then divided them into 4 groups: subjects with only PMS; subjects with only dysmenorrhea; individuals with both PMS and dysmenorrhea and normal subjects. Study design: In this cross sectional study, 897 adolescent girls who had entered menarche were recruited. Of these, 35.9% had only dysmenorrhea, 14.9% had only PMS, 32.7% had both PMS and dysmenorrhea while 16.5% had no PMS and/or dysmenorrhea (Normal). We assessed the tests for cognitive, emotional function and sleep patterns were compared for these groups. Results: Individuals in the dysmenorrhea group had significantly higher depression, aggression, insomnia, daytime sleepiness and sleep apnea scores compared to normal controls and the PMS group, but did not have significantly different cognitive ability (P value < 0.05). These differences were strongly correlated to pain intensity (P < 0.001). However, there were no significant differences between those with only PMS and control subjects with regard to cognitive ability, emotional function and sleep pattern tests. Conclusions: Dysmenorrhea is highly prevalent among adolescents and appears to be associated with depressive mood, a tendency to aggressive behavior and sleep disorders among adolescent girls. (C) 2017 Elsevier B.V. All rights reserved