Multi-biomarker pattern for tumor identification and prognosis

In last decades, the basic, clinical, and translational research efforts have been directed to the identification of standard biomarkers associated with the degree of malignancy. There is an increasingly public health concern for earlier detection of cancer development at stages in which successful treatments can be achieved. To meet this urgent clinical demand, early stage cancer biomarkers supported by reliable and robust experimental data that can be readily applicable in the clinical practice, are required. In the current standard protocols, when one or two of the canonical proliferating index biomarkers are analyzed, contradictory results are frequently reached leading to incorrect cancer diagnostic and unsuccessful therapies. Therefore, the identification of other cellular characteristics or signatures present in the tumor cells either alone or in combination with the well-established proliferation markers emerge as an alternative strategy in the improvement of cancer diagnosis and treatment. Because it is well known that several pathways and processes are altered in tumor cells, the concept of "single marker" in cancer results incorrect. Therefore, this review aims to analyze and discuss the proposal that the molecular profile of different genes or proteins in different altered tumor pathways must be established to provide a better global clinical pattern for cancer detection and prognosis.     

Acute outbreak of gnathostomiasis in a fishing community in Sinaloa, Mexico

An increasing number of human cases of gnathostomiasis have been reported in Sinaloa, Mexico, most of whom have a custom of eating of raw fish dishes such as 'cebiche'. Here we report five adult patients, three women and two men, having an acute episode of vomiting and abdominal pain a few minutes after eating a dish of cebiche prepared from a spotted sleeper perch (Eleotris picta) fished from a nearby lake in southern Sinaloa. All five patients experienced acute throat pain, chest and joint pains, headache and fever. One patient, a 55-year-old male, was hospitalized with suspected pancreatitis and pneumonia. By 8-9 days later, all five patients developed between three and 12 edematous, migrating skin lesions on the back, abdomen, upper and lower extremities, face, eye and scalp. By ELISA, all of them were sero-positive to Gnathostoma doloresi antigen and had elevated IgE levels. Eosinophilia was found in two patients. These patients lived in an agricultural and fishing community. In this community we carried out a sero-epidemiological survey and study of living conditions in a random sample of 309 individuals distributed in 74 households. Frequent consumption of raw fish was reported in 36% of households, and 12 individuals had a clinical history of migrating skin lesions. The sero-prevalence to Gnathostoma antigens was 34.95%. Five fish species and four species of ichthyophagous birds collected from three lakes in the village and a nearby estuary were infected with the advanced third-stage larvae of G. binucleatum, a species found in Ecuador and Mexico. The results describe the first known outbreak of acute gnathostomiasis on the American continent.     

Regulated mRNA stability of the Cdk inhibitor Rum1 links nutrient status to cell cycle progression

BACKGROUND: The survival of a cell depends on continuous sensing of the nutritional environment and appropriate coordination of the cell cycle. The fission yeast Schizosaccharomyces pombe is an excellent model system in which to study these processes. In the presence of nutrients, fission yeast cells grow and divide, spending most of their time in G2; when nutrients are limiting, they are promoted into mitosis and arrest the cell cycle in G1. The molecular mechanisms underlying this response are currently unknown.RESULTS: Here, we show that expression of the fission yeast Cdk inhibitor Rum1, a key regulator of Cdc2/cyclin B in G1, is subject to regulated mRNA stability in response to nutrient deprivation. In complete minimal medium, rum1 mRNAs are very unstable. Following nitrogen starvation, rum1 mRNAs are rapidly stabilized, allowing the accumulation of Rum1 protein to delay the G1 phase of the subsequent cell cycle. Instability of rum1 mRNAs in complete minimal medium depends on the presence of AU-rich elements in the 3'UTR. We also show that lack of this mechanism has consequences in the mitotic cell cycle, in meiosis, and in the control of ploidy.CONCLUSION: We propose that mRNA stability is an important mechanism to fine tune the expression of the rum1 gene, in order to allow the production of appropriate levels of Rum1 protein in response to changes in the nutritional environment.     

The association between ownership of common household devices and obesity and diabetes in high,middle and low income countries

Background:

Household devices (e.g., television, car, computer) are common in high income countries, and their use has been linked to obesity and type 2 diabetes mellitus. We hypothesized that device ownership is associated with obesity and diabetes and that these effects are explained through reduced physical activity, increased sitting time and increased energy intake.

Methods:

We performed a cross-sectional analysis using data from the Prospective Urban Rural Epidemiology study involving 153 996 adults from high, upper-middle, lower-middle and low income countries. We used multilevel regression models to account for clustering at the community and country levels.

Results:

Ownership of a household device increased from low to high income countries (4% to 83% for all 3 devices) and was associated with decreased physical activity and increased sitting, dietary energy intake, body mass index and waist circumference. There was an increased odds of obesity and diabetes with the ownership of any 1 household device compared to no device ownership (obesity: odds ratio [OR] 1.43, 95% confidence interval [CI] 1.32–1.55; diabetes: OR 1.38, 95% CI 1.28–1.50). Ownership of a second device increased the odds further but ownership of a third device did not. Subsequent adjustment for lifestyle factors modestly attenuated these associations. Of the 3 devices, ownership of a television had the strongest association with obesity (OR 1.39, 95% CI 1.29–1.49) and diabetes (OR 1.33, 95% CI 1.23–1.44). When stratified by country income level, the odds of obesity and diabetes when owning all 3 devices was greatest in low income countries (obesity: OR 3.15, 95% CI 2.33–4.25; diabetes: OR 1.97, 95% CI 1.53–2.53) and decreased through country income levels such that we did not detect an association in high income countries.

Interpretation:

The ownership of household devices increased the likelihood of obesity and diabetes, and this was mediated in part by effects on physical activity, sitting time and dietary energy intake. With increasing ownership of household devices in developing countries, societal interventions are needed to mitigate their effects on poor health.The increasing global prevalence of obesity and type 2 diabetes mellitus has been driven predominantly by increases in high income countries.^1,2 However, increases are expected in low and middle income countries, due in part to rapid development and industrialization.Proximal determinants of obesity and diabetes include energy expenditure and intake;^3–5 however, the upstream factors are complex and entail numerous environmental factors. Of these, the increased use of common household devices (e.g., televisions, cars, computers) has been linked to increased sitting, decreased physical activity, obesity, metabolic syndrome and diabetes.^6–12 Time spent watching television has also been linked to poor diet¹³ and increased caloric intake.¹⁴ However, these findings are based on studies in high income countries where the ownership of these devices is common.^15,16 In low and middle income countries, such household devices are less prevalent, but their prevalence is rapidly increasing. Studies in countries with greater variability in the ownership of household devices are needed to understand the full effect of owning such devices on the risk of obesity and diabetes.We hypothesized that the ownership of a television, car or computer would be associated with an increased risk of obesity and diabetes and that these effects would be explained by reduced physical activity, increased sitting time and increased energy intake.     

Cannabidiol Normalizes Caspase 3, Synaptophysin,and Mitochondrial Fission Protein DNM1L Expression Levels in Rats with Brain Iron Overload: Implications for Neuroprotection

We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson’s and Alzheimer’s, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.     

Effects of Lonomia obliqua caterpillar venom upon the proliferation and viability of cell lines

Many active principles produced by animals, plants and microorganisms have been employed in the development of new drugs for the treatment of human diseases. Among animals known to produce pharmacologically active molecules that interfere in human cell physiology, the caterpillar Lonomia obliqua has become the focus of toxicological studies due to recent findings about its venom constituents. The objective of this study was to investigate the effects of L. obliqua venom upon the viability and the proliferation of different cell lineages and to propose mechanisms for the herein observed induction of cell proliferation in glioma cell lines. MTT analyses indicate that L. obliqua venom increases the viability of tumor cell lines U138-MG and HT-29; on the other hand, it inhibits the viability of V-79 nontumor cells. Cell count based on the trypan blue exclusion method suggests a proliferating activity of the venom upon U138-MG cells. Exposure of U138-MG to crude venom extract led to a decrease in the production of nitric oxide, and activation of the cAMP signaling pathway inhibited the effects of the venom, indicating that these mechanisms may influence cell proliferation triggered by the venom. Despite the proliferative effects of crude venom on U138-MG and HT-29 cell cultures, a protein purified from L. obliqua hemolymph previously shown to have cytoprotective activity had no effect on U138-MG and HT-29; however, this same protein increased the viability of V-79 cells that had previously been exposed to the cytotoxic activity of the crude venom extract. This study indicates that the venom and the antiapoptotic protein act differently and have different effects on cell cultures, depending on the cell line analyzed. Biomolecules displaying either mitogenic or cytotoxic activities are of great biotechnological interest. Further studies encompassing the purification of active principles from L. obliqua venom are necessary to further elucidate its effects on different cell types.     

Effect of the commercial extract of the brown alga Ascophyllum nodosum Mont. on Kappaphycus alvarezii (Doty) Doty ex P.C. Silva in situ submitted to lethal temperatures

Kappaphycus alvarezii is being introduced in several countries and in some of them there is a need to adapt this cultivation to periods with lethal temperatures, such as the 16–18 °C that occurs in the winter in southern Brazil. Moreover, there is the need to maintain the seedlings during this lethal temperature period. Considering the promising results obtained with the commercial powder extract of Ascophyllum nodosum (Acadian marine plant extract powder—AMPEP) treatment in the cultivation of K. alvarezii in vitro and in the sea allowing more resistance to epiphytes and increasing the growth rate and carrageenan yield, it was hypothesized that seedlings previously subjected to an AMPEP treatment could be more resilient to lethal temperatures. The daily growth rate and carrageenan yield and gel quality (gel strength and gel viscosity) of K. alvarezii in vitro previously treated with AMPEP were analyzed under temperature stress. The daily growth rates and the gel strengths of the AMPEP-treated samples were increased. In spite of the lower carrageenan yield and lower gel viscosity, the values were within the ones accepted by the carrageenan industry. Thus, the treatment of the seedlings of the K. alvarezii with AMPEP solution can be used as an alternative to lower temperature effects on crops as a preventive action for the cultivation of the seedlings in tanks and in the sea in periods of low temperatures at sea.     

Effects of a commercial extract of the brown alga Ascophyllum nodosum on the biomass production of Kappaphycus alvarezii (Doty) Doty ex P. C. Silva and its carrageenan yield and gel quality cultivated in Brazil

Despite of its success, the carrageenan industry has had to cope with difficulties due to epiphyte infestations and diseases known as ice-ice. Some promising results in respect of biomass production, carrageenan yield, and protection epiphytes were obtained using a powdered extract of the brown alga Ascophyllum nodosum in Kappaphycus alvarezii seedling production. This study focused on the effects of the A. nodosum extract on the treatment of K. alvarezii cultivated on commercial floating rafts not only to evaluate improvements demonstrated in vitro but also the effects on the quality of the carrageenan. The seedlings were treated in an A. nodosum extract solution and placed alongside their controls on commercial floating rafts using the tubular net technique. Daily growth rate, carrageenan yield, gel strength, and gel viscosity were obtained over 20 and/or 40 days. After 20 days, daily growth rates showed no significant difference (p?=?0.44), while the carrageenan yield was higher in samples that were treated with the A. nodosum solution (p?<?0.001). After 40 days, both daily growth rate (p?=?000.7) and carrageenan yield (p?=?0.009) were higher in treated samples; however, gel strength was higher in control samples (p?=?0.03) as viscosity was also highest in the samples which had not been treated (p?<?0.001). The use of the A. nodosum extract treatment on the cultivation in situ of K. alvarezii was positive since after 40 days when the daily growth rate and carrageenan yield increased. In spite of the negative effect on the quality of the semi-refined carrageenan, the values were within commercial standards.