The Role of Liquid Biopsy in Early Diagnosis of Lung Cancer

Liquid biopsy is an emerging technology with a potential role in the screening and early detection of lung cancer. Several liquid biopsy-derived biomarkers have been identified and are currently under ongoing investigation. In this article, we review the available data on the use of circulating biomarkers for the early detection of lung cancer, focusing on the circulating tumor cells, circulating cell-free DNA, circulating micro-RNAs, tumor-derived exosomes, and tumor-educated platelets, providing an overview of future potential applicability in the clinical practice. While several biomarkers have shown exciting results, diagnostic performance and clinical applicability is still limited. The combination of different biomarkers, as well as their combination with other diagnostic tools show great promise, although further research is still required to define and validate the role of liquid biopsies in clinical practice.This work is financed by the ERDF—European Regional Development Fund through the Operational Programme for Competitiveness and Internationalization—COMPETE 2020 Programme and by National Funds through the Portuguese funding agency, FCT—Fundação para a Ciência e a Tecnologia within project POCI-01-0145-FEDER-030263. Authors thank Abílio Cunha and Francisco Correia for the illustration work. NC-M acknowledges the Portuguese Foundation for Science and Technology under Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

dATF4 regulation of mitochondrial folate-mediated one-carbon metabolism is neuroprotective.

Neurons rely on mitochondria as their preferred source of energy. Mutations in PINK1 and PARKIN cause neuronal death in early-onset Parkinson's disease (PD), thought to be due to mitochondrial dysfunction. In Drosophila pink1 and parkin mutants, mitochondrial defects lead to the compensatory upregulation of the mitochondrial one-carbon cycle metabolism genes by an unknown mechanism. Here we uncover that this branch is triggered by the activating transcription factor 4 (ATF4). We show that ATF4 regulates the expression of one-carbon metabolism genes SHMT2 and NMDMC as a protective response to mitochondrial toxicity. Suppressing Shmt2 or Nmdmc caused motor impairment and mitochondrial defects in flies. Epistatic analyses showed that suppressing the upregulation of Shmt2 or Nmdmc deteriorates the phenotype of pink1 or parkin mutants. Conversely, the genetic enhancement of these one-carbon metabolism genes in pink1 or parkin mutants was neuroprotective. We conclude that mitochondrial dysfunction caused by mutations in the Pink1/Parkin pathway engages ATF4-dependent activation of one-carbon metabolism as a protective response. Our findings show a central contribution of ATF4 signalling to PD that may represent a new therapeutic strategy. A video abstract for this article is available at https://youtu.be/cFJJm2YZKKM

Anacardium plants: Chemical,nutritional composition and biotechnological applications

Anacardium plants are native to the American tropical regions, and Anacardium occidentale L. (cashew tree) is the most recognized species of the genus. These species contain rich secondary metabolites in their leaf and shoot powder, fruits and other parts that have shown diverse applications. This review describes the habitat and cultivation of Anacardium species, phytochemical and nutritional composition, and their industrial food applications. Besides, we also discuss the secondary metabolites present in Anacardium plants which display great antioxidant and antimicrobial effects. These make the use of Anacardium species in the food industry an interesting approach to the development of green foods.AK. Jugran acknowledges the partial funding from Uttarakhand council for Biotechnology, Pantnagar, Uttarakhand, India (File No. UCB/R&D Project/2018-311) for this work. M. Martorell would like to thank the support offered by CONICYT PIA/APOYO CCTE AFB170007. N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and ?NORTE2020 - Northern Regional Operational Program? (NORTE-01-0145-FEDER- 000012)

Chemical Composition, Biological Activity, and Health-Promoting Effects of Withania somnifera for Pharma-Food Industry Applications

The Withania genus comes from the Solanaceae family and includes around 23 species, spread over some areas of the Mediterranean, Asia, and East Africa. Widely used in traditional medicine for thousands of years, these plants are rich in secondary metabolites, with special emphasis on steroidal lactones, named withanolides which are used as ingredients in numerous formulations for a plethora of diseases, such as asthma, diabetes, arthritis, impotence, amnesia, hypertension, anxiety, stress, cancer, neurodegenerative, and cardiovascular diseases, and many others. Among them, Withania somnifera (L.) Dunal is the most widely addressed species from a pharmacological and agroindustrial point of view. In this sense, this review provides an overview of the folk uses, phytochemical composition, and biological activity, such as antioxidant, antimicrobial, anti-inflammatory, and cytotoxic activity of W. somnifera, although more recently other species have also been increasingly investigated. In addition, their health-promoting effects, i.e., antistress, anxiolytic, adaptogenic, antirheumatoid arthritis, chemoprotective, and cardiorespiratory-enhancing abilities, along with safety and adverse effects are also discussed.N. C. -M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

Behavioural syndrome in a solitary predator is independent of body size and growth rate.

Models explaining behavioural syndromes often focus on state-dependency, linking behavioural variation to individual differences in other phenotypic features. Empirical studies are, however, rare. Here, we tested for a size and growth-dependent stable behavioural syndrome in the juvenile-stages of a solitary apex predator (pike, Esox lucius), shown as repeatable foraging behaviour across risk. Pike swimming activity, latency to prey attack, number of successful and unsuccessful prey attacks was measured during the presence/absence of visual contact with a competitor or predator. Foraging behaviour across risks was considered an appropriate indicator of boldness in this solitary predator where a trade-off between foraging behaviour and threat avoidance has been reported. Support was found for a behavioural syndrome, where the rank order differences in the foraging behaviour between individuals were maintained across time and risk situation. However, individual behaviour was independent of body size and growth in conditions of high food availability, showing no evidence to support the state-dependent personality hypothesis. The importance of a combination of spatial and temporal environmental variation for generating growth differences is highlighted

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

The deep-subsurface sulfate reducer Desulfotomaculum kuznetsovii employs two methanol-degrading pathways

Methanol is generally metabolized through a pathway initiated by a cobalamine-containing methanol methyltransferase by anaerobic methylotrophs (such as methanogens and acetogens), or through oxidation to formaldehyde using a methanol dehydrogenase by aerobes. Methanol is an important substrate in deep-subsurface environments, where thermophilic sulfate-reducing bacteria of the genus Desulfotomaculum have key roles. Here, we study the methanol metabolism of Desulfotomaculum kuznetsovii strain 17T, isolated from a 3000-m deep geothermal water reservoir. We use proteomics to analyze cells grown with methanol and sulfate in the presence and absence of cobalt and vitamin B12. The results indicate the presence of two methanol-degrading pathways in D. kuznetsovii, a cobalt-dependent methanol methyltransferase and a cobalt-independent methanol dehydrogenase, which is further confirmed by stable isotope fractionation. This is the first report of a microorganism utilizing two distinct methanol conversion pathways. We hypothesize that this gives D. kuznetsovii a competitive advantage in its natural environment.Research was funded by grants of the Division of Chemical Sciences (CW-TOP 700.55.343) and Earth and Life Sciences (ALW 819.02.014) of The Netherlands Organisation for Scientific Research (NWO), the European Research Council (ERC grant 323009), and the Gravitation grant (024.002.002) of the Netherlands Ministry of Education, Culture and Scienceinfo:eu-repo/semantics/publishedVersio