Gallic Acid: A Natural Phenolic Compound Exerting Antitumoral Activities in Colorectal Cancer via Interaction with G-Quadruplexes

Natural phenolic compounds have gained momentum for the prevention and treatment of cancer, but their antitumoral mechanism of action is not yet well understood. In the present study, we screened the antitumoral potential of several phenolic compounds in a cellular model of colorectal cancer (CRC).We selected gallic acid (GA) as a candidate in terms of potency and selectivity and extensively evaluated its biological activity. We report on the role of GA as a ligand of DNA G-quadruplexes (G4s), explaining several of its antitumoral effects, including the transcriptional inhibition of ribosomal and CMYC genes. In addition, GA shared with other established G4 ligands some effects such as cell cycle arrest, nucleolar stress, and induction of DNA damage. We further confirmed the antitumoral and G4-stabilizing properties of GA using a xenograft model of CRC. Finally, we succinctly demonstrate that GA could be explored as a therapeutic agent in a patient cohort with CRC. Our work reveals that GA, a natural bioactive compound present in the diet, affects gene expression by interaction with G4s both in vitro and in vivo and paves the way towards G4s targeting with phenolic compounds.Instituto de Salud Carlos IIIEuropean Commission PI21/00497 AC18/00008Next generation EU, Plan de Recuperacion Transformacion y Resiliencia, Agencia Estatal de Investigacion PLEC2021-008094Ministerio de Ciencia e Innovacion from Government of Spain PID2019-104416RB-I00 PID2020-120481RB-I00Ministerio de Universidades from Government of Spain FPU16/05822 FPU17/05413 FPU20/03952University of Almeria FPI-20110

Fungal Planet description sheets: 1182-1283

Novel species of fungi described in this study include those from various countries as follows: Algeria, Phaeoacremonium adelophialidum from Vitis vinifera. Antarctica, Comoclathris antarctica from soil. Australia, Coniochaeta salicifolia as endophyte from healthy leaves of Geijera salicifolia, Eremothecium peggii in fruit of Citrus australis, Microdochium ratticaudae from stem of Sporobolus natalensis, Neocelosporium corymbiae on stems of Corymbia variegata, Phytophthora kelmanii from rhizosphere soil of Ptilotus pyramidatus, Pseudosydowia backhousiae on living leaves of Backhousia citriodora, Pseudosydowia indoor oopillyensis, Pseudosydowia louisecottisiae and Pseudosydowia queenslandica on living leaves of Eucalyptus sp. Brazil, Absidia montepascoalis from soil. Chile, Ilyonectria zarorii from soil under Maytenus boaria. Costa Rica, Colletotrichum filicis from an unidentified fern. Croatia, Mollisia endogranulata on deteriorated hardwood. Czech Republic, Arcopilus navicularis from tea bag with fruit tea, Neosetophoma buxi as endophyte from Buxus sempervirens, Xerochrysium bohemicum on surface of biscuits with chocolate glaze and filled with jam. France, Entoloma cyaneobasale on basic to calcareous soil, Fusarium aconidiale from Triticum aestivum, Fusarium juglandicola from buds of Juglans regia. Germany, Tetraploa endophytica as endophyte from Microthlaspi perfoliatum roots. India, Castanediella ambae on leaves of Mangifera indica, Lactifluus kanadii on soil under Castanopsis sp., Penicillium uttarakhandense from soil. Italy, Penicillium ferraniaense from compost. Namibia, Bezerromyces gobabebensis on leaves of unidentified succulent, Cladosporium stipagrostidicola on leaves of Stipagrostis sp., Cymostachys euphorbiae on leaves of Euphorbia sp., Deniquelata hypolithi from hypolith under a rock, Hysterobrevium walvisbayicola on leaves of unidentified tree, Knufia hypolithi and Knufia walvisbayicola from hypolith under a rock, Lapidomyces stipagrostidicola on leaves of Stipagrostis sp., Nothophaeotheca mirabibensis (incl. Nothophaeotheca gen. nov.) on persistent inflorescence remains of Blepharis obmitrata, Paramyrothecium salvadorae on twigs of Salvadora persica, Preussia procaviicola on dung of Procavia sp., Sordaria equicola on zebra dung, Volutella salvadorae on stems of Salvadora persica. Netherlands, Entoloma ammophilum on sandy soil, Entoloma pseudocruentatum on nutrient poor(acid)soil, Entoloma pudens on plant debris, amongst grasses. [...]Leslie W.S. de Freitas and colleagues express their gratitude to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for scholarships provided to Leslie Freitas and for the research grant provided to André Luiz Santiago; their contribution was financed by the projects ‘Diversity of Mucoromycotina in the different ecosystems of the Atlantic Rainforest of Pernambuco’ (FACEPE–First Projects Program PPP/ FACEPE/CNPq–APQ–0842-2.12/14) and ‘Biology of conservation of fungi s.l. in areas of Atlantic Forest of Northeast Brazil’ (CNPq/ICMBio 421241/ 2017-9) H.B. Lee was supported by the Graduate Program for the Undiscovered Taxa of Korea (NIBR202130202). The study of O.V. Morozova, E.F. Malysheva, V.F. Malysheva, I.V. Zmitrovich, and L.B. Kalinina was carried out within the framework of a research project of the Komarov Botanical Institute RAS (АААА-А19-119020890079-6) using equipment of its Core Facility Centre ‘Cell and Molecular Technologies in Plant Science’. The work of O. V. Morozova, L.B. Kalinina, T. Yu. Svetasheva, and E.A. Zvyagina was financially supported by Russian Foundation for Basic Research project no. 20-04-00349. E.A. Zvyagina and T.Yu. Svetasheva are grateful to A.V. Alexandrova, A.E. Kovalenko, A.S. Baykalova for the loan of specimens, T.Y. James, E.F. Malysheva and V.F. Malysheva for sequencing. J.D. Reyes acknowledges B. Dima for comparing the holotype sequence of Cortinarius bonachei with the sequences in his database. A. Mateos and J.D. Reyes acknowledge L. Quijada for reviewing the phylogeny and S. de la Peña- Lastra and P. Alvarado for their support and help. Vladimir I. Kapitonov and colleagues are grateful to Brigitta Kiss for help with their molecular studies. This study was conducted under research projects of the Tobolsk Complex Scientific Station of the Ural Branch of the Russian Academy of Sciences (N АААА-А19-119011190112-5). E. Larsson acknowledges the Swedish Taxonomy Initiative, SLU Artdatabanken, Uppsala (dha.2019.4.3-13). The study of D.B. Raudabaugh and colleagues was supported by the Schmidt Science Fellows, in partnership with the Rhodes Trust. Gregorio Delgado is grateful to Michael Manning and Kamash Pillai (Eurofins EMLab P&K) for provision of laboratory facilities. Jose G. Maciá-Vicente acknowledges support from the German Research Foundation under grant MA7171/1-1, and from the Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE) of the state of Hesse within the framework of the Cluster for Integrative Fungal Research (IPF). Thanks are also due to the authorities of the Cabañeros National Park and Los Alcornocales Natural Park for granting the collection permit and for support during field work. The study of Alina V. Alexandrova was carried out as part of the Scientific Project of the State Order of the Government of Russian Federation to Lomonosov Moscow State University No. 121032300081-7. Michał Gorczak was financially supported by the Ministry of Science and Higher Education through the Faculty of Biology, University of Warsaw intramural grant DSM 0117600- 13. M. Gorczak acknowledges M. Klemens for sharing a photo of the Białowieża Forest logging site and M. Senderowicz for help with preparing the illustration. Ivona Kautmanová and D. Szabóová were funded by the Operational Program of Research and Development and co-financed with the European Fund for Regional Development (EFRD). ITMS 26230120004: ‘Building of research and development infrastructure for investigation of genetic biodiversity of organisms and joining IBOL initiative’. Ishika Bera, Aniket Ghosh, Jorinde Nuytinck and Annemieke Verbeken are grateful to the Director, Botanical Survey of India (Kolkata), Head of the Department of Botany & Microbiology & USIC Dept. HNB Garhwal University, Srinagar, Garhwal for providing research facilities. Ishika Bera and Aniket Ghosh acknowledge the staff of the forest department of Arunachal Pradesh for facilitating the macrofungal surveys to the restricted areas. Sergey Volobuev was supported by the Russian Science Foundation (RSF project N 19-77- 00085). Aleksey V. Kachalkin and colleagues were supported by the Russian Science Foundation (grant No. 19-74-10002). The study of Anna M. Glushakova was carried out as part of the Scientific Project of the State Order of the Government of Russian Federation to Lomonosov Moscow State University No. 121040800174-6. Tracey V. Steinrucken and colleagues were supported by AgriFutures Australia (Rural Industries Research and Development Corporation), through funding from the Australian Government Department of Agriculture, Water and the Environment, as part of its Rural Research and Development for Profit program (PRJ-010527). Neven Matočec and colleagues thank the Croatian Science Foundation for their financial support under the project grant HRZZ-IP-2018-01-1736 (ForFungiDNA). Ana Pošta thanks the Croatian Science Foundation for their support under the grant HRZZ-2018-09-7081. The research of Milan Spetik and co-authors was supported by Internal Grant of Mendel University in Brno No. IGAZF/ 2021-SI1003. K.C. Rajeshkumar thanks SERB, the Department of Science and Technology, Government of India for providing financial support under the project CRG/2020/000668 and the Director, Agharkar Research Institute for providing research facilities. Nikhil Ashtekar thanks CSIR-HRDG, INDIA, for financial support under the SRF fellowship (09/670(0090)/2020-EMRI), and acknowledges the support of the DIC Microscopy Facility, established by Dr Karthick Balasubramanian, B&P (Plants) Group, ARI, Pune. The research of Alla Eddine Mahamedi and co-authors was supported by project No. CZ.02.1.01/0.0/0.0/16_017/0002334, Czech Republic. Tereza Tejklová is thanked for providing useful literature. A. Polhorský and colleagues were supported by the Operational Program of Research and Development and co-financed with the European fund for Regional Development (EFRD), ITMS 26230120004: Building of research and development infrastructure for investigation of genetic biodiversity of organisms and joining IBOL initiative. Yu Pei Tan and colleagues thank R. Chen for her technical support. Ernest Lacey thanks the Cooperative Research Centres Projects scheme (CRCPFIVE000119) for its support. Suchada Mongkolsamrit and colleagues were financially supported by the Platform Technology Management Section, National Center for Genetic Engineering and Biotechnology (BIOTEC), Project Grant No. P19-50231. Dilnora Gouliamova and colleagues were supported by a grant from the Bulgarian Science Fund (KP-06-H31/19). The research of Timofey A. Pankratov was supported by the Russian Foundation for Basic Research (grant No. 19-04-00297a). Gabriel Moreno and colleagues wish to express their gratitude to L. Monje and A. Pueblas of the Department of Drawing and Scientific Photography at the University of Alcalá for their help in the digital preparation of the photographs, and to J. Rejos, curator of the AH herbarium, for his assistance with the specimens examined in the present study. Vit Hubka was supported by the Charles University Research Centre program No. 204069. Alena Kubátová was supported by The National Programme on Conservation and Utilization of Microbial Genetic Resources Important for Agriculture (Ministry of Agriculture of the Czech Republic). The Kits van Waveren Foundation (Rijksherbariumfonds Dr E. Kits van Waveren, Leiden, Netherlands) contributed substantially to the costs of sequencing and travelling expenses for M. Noordeloos. The work of B. Dima was supported by the ÚNKP-20-4 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund, and by the ELTE Thematic Excellence Programme 2020 supported by the National Research, Development and Innovation Office of Hungary (TKP2020-IKA-05). The Norwegian Entoloma studies received funding from the Norwegian Biodiversity Information Centre (NBIC), and the material was partly sequenced through NorBOL. Gunnhild Marthinsen and Katriina Bendiksen (Natural History Museum, University of Oslo, Norway) are acknowledged for performing the main parts of the Entoloma barcoding work. Asunción Morte is grateful to AEI/FEDER, UE (CGL2016-78946-R) and Fundación Séneca - Agencia de Ciencia y Tecnología de la Región de Murcia (20866/PI/18) for financial support. Vladimír Ostrý was supported by the Ministry of Health, Czech Republic - conceptual development of research organization (National Institute of Public Health – NIPH, IN 75010330). Konstanze Bensch (Westerdijk Fungal Biodiversity Institute, Utrecht) is thanked for correcting the spelling of various Latin epithets.Peer reviewe

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Gallic Acid: A Natural Phenolic Compound Exerting Antitumoral Activities in Colorectal Cancer via Interaction with G-Quadruplexes

Natural phenolic compounds have gained momentum for the prevention and treatment of cancer, but their antitumoral mechanism of action is not yet well understood. In the present study, we screened the antitumoral potential of several phenolic compounds in a cellular model of colorectal cancer (CRC). We selected gallic acid (GA) as a candidate in terms of potency and selectivity and extensively evaluated its biological activity. We report on the role of GA as a ligand of DNA G-quadruplexes (G4s), explaining several of its antitumoral effects, including the transcriptional inhibition of ribosomal and CMYC genes. In addition, GA shared with other established G4 ligands some effects such as cell cycle arrest, nucleolar stress, and induction of DNA damage. We further confirmed the antitumoral and G4-stabilizing properties of GA using a xenograft model of CRC. Finally, we succinctly demonstrate that GA could be explored as a therapeutic agent in a patient cohort with CRC. Our work reveals that GA, a natural bioactive compound present in the diet, affects gene expression by interaction with G4s both in vitro and in vivo and paves the way towards G4s targeting with phenolic compounds

Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription

Sleeping sickness or African trypanosomiasis is a serious health concern with an added socio-economic impact in sub-Saharan Africa due to direct infection in both humans and their domestic livestock. There is no vaccine available against African trypanosomes and its treatment relies only on chemotherapy. Although the current drugs are effective, most of them are far from the modern concept of a drug in terms of toxicity, specificity and therapeutic regime. In a search for new molecules with trypanocidal activity, a high throughput screening of 2000 microbial extracts was performed. Fractionation of one of these extracts, belonging to a culture of the fungus Amesia sp., yielded a new member of the curvicollide family that has been designated as curvicollide D. The new compound showed an inhibitory concentration 50 (IC50) 16-fold lower in Trypanosoma brucei than in human cells. Moreover, it induced cell cycle arrest and disruption of the nucleolar structure. Finally, we showed that curvicollide D binds to DNA and inhibits transcription in African trypanosomes, resulting in cell death. These results constitute the first report on the activity and mode of action of a member of the curvicollide family in T. brucei