Current Signal Transduction Therapy - Volume 9, Issue 3, 2014

Hypoxia inducible factor-1α is an important transcription factor which is necessary for hypoxic gene expression that responds to changes in oxygen level in cell. HIF-1α remained stable and active in the occurance of Fe2+ and oxygen but it is depleted through the Von Hippel Lindau protein (pVHL) or Ubiquitin or Proteosome pathway. Restriction of oxygen induces inhibition of prolyl hydroxylase and accumulation of HIF-1α which in turn translocates to the nucleus to form a heterodimer with HIF-1β. Chronic hypoxia stimulates both KLF6 and NF-ΚB gene expressions and it reduces KLF4 which further enhances8 iNOS expression. Over expression of iNOS leads to rise in NO production and increase formation of peroxynitrite (ONOO–). This event will lead to swelling of mitochondria and release cytochrome. Among the various heavy metals lead (Pb) is found to be a potent inducer of oxidative free radicals along with suppressor of cellular antioxidant defense system. The mechanism involves destruction of glutathione or inhibition of sulfhydryl dependent enzymes or altering intracellular oxidant and antioxidant balance which greatly affect cellular integrities. Heavy metals like lead (Pb), nickel (Ni) and cobalt (Co) can activate the hypoxia signaling pathways through Akt/ERK1/2 and induce HIF-1α accumulation. This review analyzed the significant impact of sustained hypoxia in physiological system alone or along with simultaneous exposure of lead and possible protective role of vitamin C as antioxidant in rats.

Lung cancer is a global public health concern with the highest morbidity and mortality among all cancers. Biomarkers can be used for early lung cancer detection, prognostication and optimal treatment. Research on biomarkers will enable more effective therapy for each individual patient. Great progress has been made in biomarker discovery with more understanding involved in lung cancer. Lung cancer biomarkers can be classified into Proteins, DNAs, Epigenomics, and RNAs according to their biochemical properties. Here, we will discuss the most common biomarkers for lung cancer.

In the last several years, bone tumor related microRNA research showed an explosive growth. MicroRNA was found to have a high or low expression level in bone tumor tissue and some microRNAs proved to be the biomarker for poor prognosis. The majority of research was focused on osteosarcoma and Ewing sarcoma. Many tumor associated molecules, including oncogenes and tumor suppressor genes, were found to be the direct targets for microRNA, and enhanced microRNA may play the regulatory role in tumor development. In the bone tumor cell lines, overexpression of microRNA could promote or inhibit the tumor growth, migration, invasion, and metastasis, especially for osteosarcoma and Ewing sarcoma. Many key molecules proved important for tumor genesis were found directly binding to the related microRNA, and whose expression level was down regulated. This may provide a novel therapeutic target for bone tumor. Large scale clinical samples detection and high through-put microarray assay have demonstrated microRNA might be applied to predict and diagnose the bone tumor. MicroRNA in serum was also proved significant as a biomarker for bone tumor.

Coronary artery disease (CAD) is a type of heart disease with high incidence and mortality in Europe and the United States as well as in Asian countries. miRNA is a kind of regulatory RNA which controls gene expression by binding to complementary sequences of their targets, thus promotes RNA degradation and/or inhibits protein translation. Recent studies showed miRNAs function as key mediators in the pathological process of CAD which supply potential targets for CAD treatment. Expression of several miRNAs is heart-specific and CAD-specific, in addition to the signature that miRNAs are stable in plasma and other body fluids, makes miRNAs potential biomarkers for CAD diagnosis, therapeutic efficacy and prognosis. Here, the review will summarize the development of miRNAs involved in CAD.

Sleep is a vital segment of life, however, the mechanisms of diet promoting sleep are unclear and are the focus of research. Insomnia is a general sleep disorder and functional foods are known to play a key role in the prevention of insomnia. A number of studies have demonstrated that major insomnia risk factors in human being are less functional foods in dietary. There are higher functional components in functional foods promoting sleep, including tryptophan, GABA, calcium, potassium, melatonin, pyridoxine, L-ornithine and hexadecanoic acid; but wake-promoting neurochemical factors include serotonin, noradrenalin, acetylcholine, histamine, orexin and so on. The factors promoting sleep in human being are the functional foods include barley grass powder, whole grains, maca, panax, Lingzhi, asparagus powder, lettuce, cherry, kiwifruits, walnut, schisandra wine, and milk; Barley grass powder with higher GABA and calcium, as well as potassium is the most ideal functional food promoting sleep, however, the sleep duration for modern humans is associated with food structure of ancient humans. In this review, we put forward possible mechanisms of functional components in foods promoting sleep. Although there is clear relevance between sleep and diet, their molecular mechanisms need to be studied further.

Background: Pancreatic cancer is characterized by severe hypoxic regions, and in order to survive and proliferate under such adverse tumor microenvironment with limited supplies of nutrients and oxygen, pancreatic cancer cells must rely on their ability to reprogram canonical metabolic pathways. Thus, the understanding of pancreatic cellular metabolic transformation could shed light on the discovery of novel therapeutic approaches. Methods: The physiological role of FBP1 (Fructose-1,6-bisphosphatase 1) in pancreatic cancer proliferation and glycolysis was assessed by lentivirus mediated introduction of this enzyme into PANC-1 cells. Subsequently, the reasons accounted for the down-regulation of FBP1 were explored. Results: FPB1 was a negative regulator of pancreatic cancer cell proliferation and invasiveness. Moreover, it plays an adverse role in glycolysis by reduction in glucose uptake, lactate production and transcription in key glycolytic genes. In the end, our preliminary data indicates that FPB1 was epigenetically silenced in PANC-1 cells through DNA methylation and chromatin modifications. Conclusion: FBP1 is a negative regulator of pancreatic cancer cell proliferation, invasion and glycolysis. Moreover, FBP1 was epigenetically silenced through DNA methylation and chromatin modification.

Background: This study aimed to compare the improvement in the quality of life (QoL) in the long-term follow-up of 12 to 24 months after transcatheter aortic valve implantation (TAVI) therapy for old people with severe aortic stenosis. Methods: According to the guidelines provided by PRISMA, published studies till 15 June, 2014 were retrieved from Google Scholar, Pubmed, Embase and CNKI. Health-related QoL was evaluated at beginning and at 12 to 24 months with five kinds of instruments. Funnel plots were used to test the potential publication bias, and analyze the source of heterogeneity, such as meta-regression, subgroup and sensitivity. Results: Our meta-analysis involved ten studies with 1359 patients. Preprocedural summary 12-item Short Form (SF-12) physical and mental scores showed a significant improvement after one year after TAVI [weighted mean difference (WMD): -10.61, 95% confidence interval (CI): -15.06, -6.15; WMD: -6.39, 95%CI: -9.08, -3.70; respectively]. One year follow-up visit after TAVI revealed significantly improved QoL compared to baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQol (EQ-5D) (WMD: -29.44, 95%CI: -33.29, -26.58; WMD: -0.09, 95%CI: -0.12, -0.06; respectively). At 12 to 24 months, weighted mean 36-item Short-Form (SF-36) physical improved by 16.96 points (95%CI: -27.77, -6.16) and SF-36-mental improved by 5.57 points (95%CI: -9.96, -1.19); weighted mean Minnesota Living with Heart Failure Questionnaire (MLHFQ) decreased by 22.29 points (95%CI: 16.09, 28.48). Conclusion: This technique provides a promising therapy approach for old patients with severe symptomatic aortic stenosis in high-risk surgery, and there are significant improvements for this group in health-related quality of life in the follow-up.