Pancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with ...pancreatic cancer is urgently needed to explore novel venues of diagnostics and treatment of this dismal disease. While there is mounting evidence that long noncoding RNAs (lncRNAs) transcribed from intronic and intergenic regions of the human genome may play different roles in the regulation of gene expression in normal and cancer cells, their expression pattern and biological relevance in pancreatic cancer is currently unknown. In the present work we investigated the relative abundance of a collection of lncRNAs in patients' pancreatic tissue samples aiming at identifying gene expression profiles correlated to pancreatic cancer and metastasis.
Custom 3,355-element spotted cDNA microarray interrogating protein-coding genes and putative lncRNA were used to obtain expression profiles from 38 clinical samples of tumor and non-tumor pancreatic tissues. Bioinformatics analyses were performed to characterize structure and conservation of lncRNAs expressed in pancreatic tissues, as well as to identify expression signatures correlated to tissue histology. Strand-specific reverse transcription followed by PCR and qRT-PCR were employed to determine strandedness of lncRNAs and to validate microarray results, respectively.
We show that subsets of intronic/intergenic lncRNAs are expressed across tumor and non-tumor pancreatic tissue samples. Enrichment of promoter-associated chromatin marks and over-representation of conserved DNA elements and stable secondary structure predictions suggest that these transcripts are generated from independent transcriptional units and that at least a fraction is under evolutionary selection, and thus potentially functional.Statistically significant expression signatures comprising protein-coding mRNAs and lncRNAs that correlate to PDAC or to pancreatic cancer metastasis were identified. Interestingly, loci harboring intronic lncRNAs differentially expressed in PDAC metastases were enriched in genes associated to the MAPK pathway. Orientation-specific RT-PCR documented that intronic transcripts are expressed in sense, antisense or both orientations relative to protein-coding mRNAs. Differential expression of a subset of intronic lncRNAs (PPP3CB, MAP3K14 and DAPK1 loci) in metastatic samples was confirmed by Real-Time PCR.
Our findings reveal sets of intronic lncRNAs expressed in pancreatic tissues whose abundance is correlated to PDAC or metastasis, thus pointing to the potential relevance of this class of transcripts in biological processes related to malignant transformation and metastasis in pancreatic cancer.
Animal-induced galls are considered extended phenotypes of their inducers, and therefore plant morphogenesis and metabolism may vary according to the species of gall inducers. The alterations in ...vacuolar and apoplastic polyphenols, carotenoids, chlorophyll fluorescence rates, PSII quantum yield, and phospholipid peroxidation were studied in galls induced by Ditylenchus gallaeformans (Nematoda) on Miconia albicans and M. ibaguensis (Melastomataceae), and by an unidentified Eriophyidae (Acarina) on M. ibaguensis. The focus currently addressed is gall metabolism as the extended phenotype of the gall inducers, and the neglected determination of gall functionalities over host plant peculiarities. Galls induced by D. gallaeformans on M. albicans and by the Eriophyidae on M. ibaguensis have increased accumulation of apoplastic and vacuolar phenolics, which is related to the control of phospholipid peroxidation and photoprotection. The galls induced by D. gallaeformans on M. ibaguensis have higher carotenoid and vacuolar polyphenol contents, which are related to excessive sunlight energy dissipation as heat, and photoprotection. Accordingly, antioxidant strategies varied according to the gall-inducing species and to the host plant species. The distinctive investments in carotenoid and/or in polyphenol concentrations in the studied galls seemed to be peculiar mechanisms to maintain oxidative homeostasis. These mechanisms were determined both by the stimuli of the gall-inducing organism and by the intrinsic physiological features of the host plant species. Therefore, the roles of both associated organisms in host plant-galling organisms systems over gall metabolism is attested.
In the last two decades, several studies have evaluated plant physiology, growth and survival under forecasted climate changes and the effects of these environmental factors in plants are started to ...be understood. However, there are few studies evaluating such effects at the tissue or cellular level, especially for plants with photosynthetic C4 metabolism that are believed to respond less to elevated CO2 concentration. For this reason, we tested maize and pearl millet plants to consider cellular physiological responses to induce osmotic stress and acute heat shock. Plants were grown under elevated CO2 concentration and temperature, simulating global climate changes and then were subjected to osmotic stress and acute heat shock in vitro. The results indicated that the growth under elevated CO2 and temperature improved cellular tolerance to osmotic stress and acute heat shock for both species, but maize seemed to benefit more from increased CO2 concentration whereas pearl millet seemed to benefit more from increased temperature. Taken together, the results indicated that the current and expected global climate changes, besides operating differentially in these two species, can similarly affect other C4 plant species in different ecosystems whether undisturbed or managed.
Several studies have evaluated plant physiology, growth and survival under forecasted climate changes, however, there are few studies evaluating such effects at the tissue or cellular level, especially for plants with photosynthetic C4 metabolism. Maize and pearl millet plants were grown under elevated CO2 concentration and temperature, simulating global climate changes. The results indicated that the growth under elevated CO2 and temperature improved cellular tolerance to osmotic stress and acute heat shock for both species, but maize seemed to benefit more from increased CO2 concentration whereas pearl millet seemed to benefit more from increased temperature.
Lifestyle interventions including exercise programmes are cornerstones in the prevention of obesity-related diabetes. In this
study, we demonstrate that a single bout of exercise inhibits high-fat ...diet-induced insulin resistance. Diet-induced obesity
(DIO) increased the expression and activity of the protein tyrosine phosphatase 1B (PTP1B) and attenuated insulin signalling
in gastrocnemius muscle of rats, a phenomenon which was reversed by a single session of exercise. In addition, DIO was observed
to lead to serine phosphorylation of insulin receptor substrate 1 (IRS-1), which was also reversed by exercise in muscle in
parallel with a reduction in c-Jun N-terminal kinase (JNK) activity. Thus, acute exercise increased the insulin sensitivity
during high-fat feeding in obese rats. Overall, these results provide new insights into the mechanism by which exercise restores
insulin sensitivity.
Prolonged exercise of medium to high intensity is known to promote a substantial effect on the energy balance of rats. In male rats, moderately to severely intense programs lead to a reduction in ...food intake. However, the exact causes for the appetite-suppressive effects of exercise are not known. Here, we show that intracerebroventricular insulin or leptin infusion reduced food intake in exercised rats to a greater extent than that observed in control animals. Exercise was associated with a markedly increased phosphorylation/activity of several proteins involved in leptin and insulin signal transduction in the hypothalamus. The regulatory role of interleukin (IL)-6 in mediating the increase in leptin and insulin sensitivity in hypothalamus was also investigated. Treatment with insulin or leptin markedly reduced food intake in exercised rats that were pretreated with vehicle, although no increase in sensitivity to leptin- and insulin-induced anorexia after pretreatment with anti-IL-6 antibody was detected. The current study provides direct measurements of leptin and insulin signaling in the hypothalamus and documents increased sensitivity to these hormones in the hypothalamus of exercised rats in an IL-6-dependent manner. These findings provide support for the hypothesis that the appetite-suppressive actions of exercise may be mediated by the hypothalamus.
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•Endogenous NO levels are higher in roots of Al-tolerant wheat.•NO precursors decrease Al accumulation in wheat root cells.•NO precursors stimulate auxin flow towards roots in ...Al-treated wheat.•Al-induced oxidative stress is attenuated in wheat roots by NO precursors.•Increased endogenous NO content contribute, in part, to wheat Al tolerance.
Aluminum (Al) is an element widely distributed in soils, even though Al3+ is one of the most detrimental cations to plant growth. The effect of nitric oxide (NO) precursors on indole-3-acetic acid (IAA) flow towards roots upon Al treatment is herein reported using two Triticum aestivum (wheat) cultivars with recognized differential Al tolerance. Roots of Al-tolerant seedlings with no treatment (control) accumulated higher amounts of NO than Al-sensitive ones. The treatment with Al further stimulated NO production in root cells while root exposure to NO3−, L-arginine (Arg) or the NO donor S-nitrosoglutathione (GSNO) decreased both Al and lipid peroxide accumulation in both cultivars. Regardless of the cultivar, NO3−, Arg or GSNO prevented the blockage of IAA flow towards roots. Overall, the treatment of wheat roots with NO precursors prior to Al treatment effectively guarantees normal IAA flow towards roots, a condition that favors the organ’s growth and development.
The pathogenesis of cancer anorexia is multifactorial and associated with disturbances of the central physiological mechanisms controlling food intake. However, the neurochemical mechanisms ...responsible for cancer-induced anorexia are unclear. Here we show that chronic infusion of 5-amino-4imidazolecarboxamide-riboside into the third cerebral ventricle and a chronic peripheral injection of 2 deoxy-d-glucose promotes hypothalamic AMP-activated protein kinase (AMPK) activation, increases food intake, and prolongs the survival of anorexic tumor-bearing (TB) rats. In parallel, the pharmacological activation of hypothalamic AMPK in TB animals markedly reduced the hypothalamic production of inducible nitric oxide synthase, IL-1β, and TNF-α and modulated the expression of proopiomelanocortin, a hypothalamic neuropeptide that is involved in the control of energy homeostasis. Furthermore, the daily oral and intracerebroventricular treatment with biguanide antidiabetic drug metformin also induced AMPK phosphorylation in the central nervous system and increased food intake and life span in anorexic TB rats. Collectively, the findings of this study suggest that hypothalamic AMPK activation reverses cancer anorexia by inhibiting the production of proinflammatory molecules and controlling the neuropeptide expression in the hypothalamus, reflecting in a prolonged life span in TB rats. Thus, our data indicate that hypothalamic AMPK activation presents an attractive opportunity for the treatment of cancer-induced anorexia.
In the last two decades, several studies have evaluated plant physiology, growth and survival under forecasted climate changes and the effects of these environmental factors in plants are started to ...be understood. However, there are few studies evaluating such effects at the tissue or cellular level, especially for plants with photosynthetic C4 metabolism that are believed to respond less to elevated CO
2
concentration. For this reason, we tested maize and pearl millet plants to consider cellular physiological responses to induce osmotic stress and acute heat shock. Plants were grown under elevated CO
2
concentration and temperature, simulating global climate changes and then were subjected to osmotic stress and acute heat shock in vitro. The results indicated that the growth under elevated CO
2
and temperature improved cellular tolerance to osmotic stress and acute heat shock for both species, but maize seemed to benefit more from increased CO
2
concentration whereas pearl millet seemed to benefit more from increased temperature. Taken together, the results indicated that the current and expected global climate changes, besides operating differentially in these two species, can similarly affect other C4 plant species in different ecosystems whether undisturbed or managed.
Proper activation of phosphoinositide 3-kinase-Akt pathway is critical for the prevention of tumorigenesis. Recent data have characterized a negative feedback loop, wherein mammalian target of ...rapamycin (mTOR) blocks additional activation of the Akt/mTOR pathway through inhibition insulin receptor substrate 1 (IRS-1) function. However, the potential of IRS-1 inhibition during rapamycin treatment has not been examined. Herein, we show that IRS-1 antisense oligonucleotide and rapamycin synergistically antagonize the activation of mTOR in vivo and induced tumor suppression, through inhibition of proliferation and induction of apoptosis, in prostate cancer cell xenografts. These data demonstrate that the addition of agents that blocks IRS-1 potentiate the effect of mTOR inhibition in the growth of prostate cancer cell xenografts.
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