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News Article | November 28, 2016
Site: www.eurekalert.org

A team of scientists at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), led by Prof. Francisco Sánchez-Madrid, has characterized a cell signal that impedes intercellular communication and could play a central role in biomedical strategies such as gene therapy, vaccine design, and immunotherapy. The study, published today in Nature Communications, characterizes a signal that impedes the secretion of nanovesicles called exosomes. Cells secrete exosomes as a means of intercellular communication; however, certain viruses can use exosomes as "Trojan horses" to facilitate their propagation and entry into neighboring cells. The signal, called ISGylation, has in the past been viewed mainly as an antiviral signal, although some studies show that it can also be activated by other stimuli such as a lack of oxygen, aging, or cancer. "In these situations, the secretion of exosomes, and therefore communication between cells, can be affected by this modification," explains Dr. Carolina Villarroya. The research team is dedicated to decoding the processes that control exosome secretion and exploring potential biomedical applications. As Dr. Sánchez-Madrid explains, "as well as acting as messengers in intercellular communication, exosomes are potential tools for gene therapy, vaccine design, and immunotherapy." Several clinical trials are underway to assess new treatments using this approach. The Nature Communications article describes how an antiviral signal activates the programmed degradation of proteins involved in exosome degradation. According to Villarroya, this signal "marks specific proteins located in endosomes, the place where exosomes are formed. This mark redirects these proteins toward the degradation pathway and impedes exosome secretion." Sánchez-Madrid points out that this newly identified mechanism, through which cells defend themselves against infection by activating the degradation of their own proteins, "could also be exploited by external agents for their propagation." The study was carried out by CNIC-UAM scientists Carolina Villarroya, Francesc Baixauli, Irene Fernández, María Mittelbrunn, Daniel Torralba, and Olga Moreno, in collaboration with Susana Guerra (UAM) and Carles Enrich (IDIBAPS).


News Article | December 19, 2016
Site: www.eurekalert.org

Scientists at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) have demonstrated the fundamental role of the hypoxia response in the correct formation of the heart ventricles. Hypoxia, a drop in the levels of oxygen, triggers a complex adaptive response to reestablish the tissue supply of nutrients and oxygen. The key elements of this response are the hypoxia-inducible transcription factors, or HIFs, which mediate the activation of a multitude of genes that guarantee a transitory adaptation to the lack of oxygen. This pathway plays a well-established role in cancer and tumor metastasis, but its participation in physiological processes has been less explored. The CNIC team, led by Dr. Silvia Martin-Puig, has identified discrete metabolic territories within the embryonic myocardium; the study uncovers the molecular mechanisms through which HIF1 establishes this metabolic boundary between different types of cardiomyocytes to regulate the maturation of the contractile muscle and the establishment of the conduction system. The study, published in Developmental Cell, describes the importance of the hypoxia pathway in an essential physiological process, the formation of the heart chambers, establishing the importance of hypoxia outside of disease settings. The study findings could help to identify mechanisms underlying congenital heart conditions associated with hypoxia or metabolic alterations, such as preeclampsia or gestational diabetes. Moreover, comments Dr. Martin-Puig, these mechanisms "could be of clinical interest in the treatment of disorders affecting the adult heart. In myocardial infarction, the lack of oxygen, or ischemia, induces the activation of HIF1, which could reprogram the metabolism of the mature myocardium toward an embryonic pattern." These metabolic adaptations linked to HIF1 activation "could also operate in other cardiomyopathies whose development is associated with energetic alterations." Until now, heart metabolism was thought to be dominated by glucose consumption in at embryonic stages followed by a switch just after birth to the energetically more efficient fatty acid oxidation, to take advantage of the increased oxygen availability. The research by Dr. Martin-Puig's team now challenges this model, describing a new point of regulation during gestation related to a decrease in the cardiac levels of HIF1. The CNIC research team describe how the distribution of HIF1 in distinct zones of the developing heart establishes compartments with different metabolic programs. "The compact myocardium, which gives rise to the contractile muscle in the mature heart, has high levels of HIF1 and a glycolytic metabolism," explains first author Iván Menéndez-Montes. In contrast, "the trabecular myocardium, which gives rise to the ventricular conduction system responsible for transmitting cardio-electric stimuli, expresses negligible levels of HIF1 and glycolytic enzymes, instead having a higher mitochondrial activity than the compact myocardium." The authors describe the mechanism through which this metabolic boundary disappears at midgestation (day 14.5 in the mouse), with a sharp drop in the expression of glycolytic enzymes and a simultaneous increase in the number of mitochondria and the activity of genes involved in fatty acid metabolism. This change in the metabolic program coincides with the loss of HIF1 expression in the heart. Although the scientists are continuing their investigation into the mechanisms that regulate HIF1 fluctuations during development, their work with several genetic models has already demonstrated that maintaining HIF1 activation beyond midgestation causes severe structural defects incompatible with life. Dr. Martin-Puig points out that "the sustained presence of HIF1 maintains a metabolic program based on glucose consumption and causes a sharp decline in the number and activity of cardiac mitochondria, impeding the switch to oxidative metabolism. These alterations to the metabolic program and HIF1 expression in the embryo compromise the contractile capacity of the myocardium and significantly impair heart function." In conclusion, the progressive transition to oxidative metabolism in the embryonic myocardium parallels the gradual loss of HIF1; these changes are necessary for correct maturation and contraction of the muscle and to preserve the genetic program that establishes the cardiac conduction system, permitting the correct formation of the ventricles. In addition to clarifying the direct involvement of HIF1 in the link between metabolic status and myocardial maturation and function, the study "opens the route to new therapeutic interventions" targeting HIF1 or metabolic status to improve cardiac function in cardiovascular diseases.


News Article | December 8, 2016
Site: www.realwire.com

The Chinese government has accredited .XYZ, distributed exclusively by CentralNic, to host Chinese websites. London UK, Thursday 8th December 2016. .XYZ, the planet’s most popular new generic Top Level Domain (new gTLD) has been accredited by the Chinese Ministry of Industry and Information Technology (MIIT). This approval, which is one of the first for new gTLDs, allows companies and people in China to use .XYZ web-addresses to host their websites. Since its launch in 2014, .XYZ has dominated the new Top-Level Domain space. One in every four new-style web-addresses registered ends in .XYZ. The popularity of .XYZ is such that, not only do millions of small business use them, but so do Google, Mark Zuckerberg and the founders of Skype. CentralNic Plc, .XYZ’s exclusive global distributor, is also the world-leader in new gTLDs. CentralNic has worked closely with .XYZ to put in place a customised technology platform. The global internet regulator ICANN and China’s MIIT both approved this leading-edge solution. This secures .XYZ’s place among the first batch of non-Chinese “not-COM” domains approved for Chinese citizens. “Accreditation in China is one of .XYZ's most significant milestones to date” said Daniel Negari, CEO of .XYZ. “CentralNic has been an amazing back end partner of XYZ. It went above and beyond its contractual requirements to help navigate through foreign policies and technical requirements.” More retailers (“registrars”) sell XYZ than any other new Top-Level Domain name. It is already a multi-million seller in China. Many Chinese citizens have obtained the .XYZ they wanted in anticipation of the MIIT accreditation. “I am delighted that our partner .XYZ has received its MIIT accreditation”, said Ben Crawford, CEO at CentralNic. “.XYZ has always been the dominant new TLD, and China the biggest new TLD market. It’s an exciting moment that should see .XYZ grow even faster.” With over 6.5 million domain names already registered, .XYZ is leading the field in this new but high growth area of the Internet. The addition of MIIT accreditation will make .XYZ web-addresses even more accessible in China. “CentralNic worked hard to get our solution approved by ICANN and pass critical ICANN testing which is required to implement the solution we developed together” Negari added. “We look forward to our continued partnership with CentralNic to make .XYZ the go-to domain extension for every business and individual in China.” MIIT-accredited .XYZ web addresses will be available via Chinese domain registrars from the 16th of December 2016. About CentralNic Group plc CentralNic (LSE: CNIC) is a London-based AIM-listed company. It earns revenues from the worldwide sales of internet domain names using its proprietary technology platform. It sells these domain names on an annual subscription basis. Customers pay for domain names upfront, making CentralNic a cash-generative business with annuity revenue streams. CentralNic comprises three business lines within the domain name industry. It operates a global wholesale network, supplying domain names to over 1,500 vendors in 77 countries. CentralNic is the exclusive wholesaler for over 30 new Top-Level Domain extensions (the new alternatives to .com and .net). These include .xyz, .site, .online, .website, .space, and .tech. These extensions rank among the top twenty five most subscribed new Top-Level Domains. One in three of all domains registered under new TLDs globally uses the CentralNic platform. This positions CentralNic as the leading global supplier with approximately eight million of these domains under management. CentralNic is also a leading global domain name retailer, with retail websites including internetbs.net, buydomains.london and domain.luxury. After recently acquiring Instra Group, CentralNic Group now includes instra.com and a number of other leading retail websites. Through its enterprise programme, CentralNic supplies domain names (including high-value premium domain names), software and services directly to large companies and governments. For more information please visit: www.centralnic.com About Beijing XYZ Technology Co. LTD Beijing XYZ is the Chinese registry operator of the world's most popular new domain, .xyz, as well as .College, .Rent, .Security, .Protection, and .Theatre. Through a joint venture, the company also offers some of the internet's most valuable real estate ending in .Cars, .Car, and .Auto. Founded in 2011, the company is led by CEO and Founder Daniel Negari, a visionary internet entrepreneur with years of experience in the domain industry. Learn more about XYZ in recent featured press such as Fox Business News with Maria Bartiromo, The Telegraph or at http://www.gen.xyz/. More information about .xyz can be found at www.gen.xyz/China, www.weibo.com/genxyz, by joining XYZ’s official QQ group: 295605448, or on WeChat: wwwgenxyz.


Arduini A.,University of Valencia | Serviddio G.,University of Foggia | Escobar J.,University of Valencia | Tormos A.M.,University of Valencia | And 4 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2011

Chronic cholestasis is characterizedby mitochondrial dysfunction, associated with loss of mitochondrialmembrane potential, decreased activities of respiratory chaincomplexes, and ATP production. Our aim was to determine themolecular mechanisms that link long-term cholestasis to mitochondrialdysfunction. We studied a model of chronic cholestasis inducedby bile duct ligation in rats. Key sensors and regulators of theenergetic state and mitochondrial biogenesis, mitochondrial DNA(mtDNA)-to-nuclear DNA (nDNA) ratio (mtDNA/nDNA) relativecopy number, mtDNA deletions, and indexes of apoptosis (BAX,BCL-2, and cleaved caspase 3) and cell proliferation (PCNA) wereevaluated. Our results show that long-term cholestasis is associatedwith absence of activation of key sensors of the energetic state,evidenced by decreased SIRT1 and pyruvate dehydrogenase kinaselevels and lack of AMPK activation. Key mitochondrial biogenesisregulators (PGC-1α and GABP-α) decreased and NRF-1 was nottranscriptionally active. Mitochondrial transcription factor A (TFAM)protein levels increased transiently in liver mitochondria at 2 wk afterbile duct ligation, but they dramatically decreased at 4 wk. ReducedTFAM levels at this stage were mirrored by a marked decrease (65%)in mtDNA/nDNA relative copy number. The blockade of mitochondrialbiogenesis should not be ascribed to activation of apoptosis orinhibition of cell proliferation. Impaired mitochondrial turnover andloss of the DNA stabilizing effect of TFAM are likely the causativeevent involved in the genetic instability evidenced by accumulation ofmtDNA deletions. In conclusion, the lack of stimulation of mitochondrialbiogenesis leads to mtDNA severe depletion and deletions inlong-term cholestasis. Hence, long-term cholestasis should be considereda secondary mitochondrial hepatopathy. © 2011 the American Physiological Society.


Nunez-Andrade N.,CNIC | Lamana A.,Hospital Of La Princesa | Sancho D.,CNIC | Gisbert J.P.,Hospital Universitario Of La Princesa | And 3 more authors.
Journal of Pathology | Year: 2011

P-selectin glycoprotein ligand-1 (PSGL-1), a leukocyte adhesion receptor that interacts with selectins, induces a tolerogenic programme in bone marrow-derived dendritic cells (DCs), which in turn promotes the generation of T regulatory (Treg) lymphocytes. In the present study, we have used a mouse model of dextran sulphate sodium (DSS)-induced colitis and studied the characteristics of the inflammatory cell infiltrate in the lamina propria (LP), mesenteric lymph nodes (mLNs) and Peyer's patches (PPs) to assess the possible role of PSGL-1 in the modulation of the enteric immune response. We have found that untreated PSGL-1-deficient mice showed an altered proportion of innate and adaptive immune cells in mLNs and PPs as well as an activated phenotype of macrophages and DCs in the colonic LP that mainly produced pro-inflammatory cytokines. Administration of an anti-PSGL-1 antibody also reduced the total numbers of macrophages, DCs and B cells in the colonic LP, and induced a lower expression of MHC-II by DCs and macrophages. After DSS treatment, PSGL-1 -/- mice developed colitis earlier and with higher severity than wild-type (WT) mice. Accordingly, the colonic LP of these animals showed an enhanced number of Th1 and Th17 lymphocytes, with enhanced synthesis of IL-1α, IL-6 and IL-22, and increased activation of LP macrophages. Together, our data indicate that PSGL-1 has a relevant homeostatic role in the gut-associated lymphoid tissue under steady-state conditions, and that this adhesion receptor is able to down-regulate the inflammatory phenomenon in DSS-induced colitis. © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Nurmi T.,University of Eastern Finland | Mursu J.,University of Eastern Finland | Penalvo J.L.,CNIC | Poulsen H.E.,Copenhagen University | Voutilainen S.,University of Eastern Finland
British Journal of Nutrition | Year: 2010

Intake of lignans has been assessed in different study populations, but so far none of the studies has compared the daily intake of lignans and the urinary excretion of plant and enterolignans. We assessed the intake of lariciresinol, pinoresinol, secoisolariciresinol and matairesinol in 100 Finnish men consuming their habitual omnivorous diet, and measured the 24h urinary excretion of plant and enterolignans to compare the intake and metabolism. Dietary determinants of lignan intake and their urinary excretion were also determined. The mean intake of lignans was 1224 (sd 539) g/d, of which lariciresinol and pinoresinol covered 78%. Almost half (47%) of the intake of lignans was explained by the intake of rye products, berries, coffee, tea and roots. The urinary excretion of plant lignans corresponded to 17% and enterolignans to 92% of the intake of lignans. The urinary excretion of plant lignans was explained 14% by the intake of rye products and intake of coffee, and consequently 3-7% by the intake of water-insoluble fibre. The urinary excretion of enterolactone was explained 11% by the intake of vegetables and rye products, 14% by the intake of water-soluble fibre and only 4% by the intake of lariciresinol. Although the assessed intake of lignans corresponded well with the urinary excretion of lignans, the enterolactone production in the human body depended more on the dietary sources of lignans than the absolute intake of lignans. © 2010 The Author.


News Article | December 22, 2016
Site: www.medicalnewstoday.com

Scientists at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) have demonstrated the fundamental role of the hypoxia response in the correct formation of the heart ventricles. Hypoxia, a drop in the levels of oxygen, triggers a complex adaptive response to reestablish the tissue supply of nutrients and oxygen. The key elements of this response are the hypoxia-inducible transcription factors, or HIFs, which mediate the activation of a multitude of genes that guarantee a transitory adaptation to the lack of oxygen. This pathway plays a well-established role in cancer and tumor metastasis, but its participation in physiological processes has been less explored. The CNIC team, led by Dr. Silvia Martin-Puig, has identified discrete metabolic territories within the embryonic myocardium; the study uncovers the molecular mechanisms through which HIF1 establishes this metabolic boundary between different types of cardiomyocytes to regulate the maturation of the contractile muscle and the establishment of the conduction system. The study, published in Developmental Cell, describes the importance of the hypoxia pathway in an essential physiological process, the formation of the heart chambers, establishing the importance of hypoxia outside of disease settings. The study findings could help to identify mechanisms underlying congenital heart conditions associated with hypoxia or metabolic alterations, such as preeclampsia or gestational diabetes. Moreover, comments Dr. Martin-Puig, these mechanisms "could be of clinical interest in the treatment of disorders affecting the adult heart. In myocardial infarction, the lack of oxygen, or ischemia, induces the activation of HIF1, which could reprogram the metabolism of the mature myocardium toward an embryonic pattern." These metabolic adaptations linked to HIF1 activation "could also operate in other cardiomyopathies whose development is associated with energetic alterations." Until now, heart metabolism was thought to be dominated by glucose consumption in at embryonic stages followed by a switch just after birth to the energetically more efficient fatty acid oxidation, to take advantage of the increased oxygen availability. The research by Dr. Martin-Puig's team now challenges this model, describing a new point of regulation during gestation related to a decrease in the cardiac levels of HIF1. The CNIC research team describe how the distribution of HIF1 in distinct zones of the developing heart establishes compartments with different metabolic programs. "The compact myocardium, which gives rise to the contractile muscle in the mature heart, has high levels of HIF1 and a glycolytic metabolism," explains first author Iván Menéndez-Montes. In contrast, "the trabecular myocardium, which gives rise to the ventricular conduction system responsible for transmitting cardio-electric stimuli, expresses negligible levels of HIF1 and glycolytic enzymes, instead having a higher mitochondrial activity than the compact myocardium." The authors describe the mechanism through which this metabolic boundary disappears at midgestation (day 14.5 in the mouse), with a sharp drop in the expression of glycolytic enzymes and a simultaneous increase in the number of mitochondria and the activity of genes involved in fatty acid metabolism. This change in the metabolic program coincides with the loss of HIF1 expression in the heart. Although the scientists are continuing their investigation into the mechanisms that regulate HIF1 fluctuations during development, their work with several genetic models has already demonstrated that maintaining HIF1 activation beyond midgestation causes severe structural defects incompatible with life. Dr. Martin-Puig points out that "the sustained presence of HIF1 maintains a metabolic program based on glucose consumption and causes a sharp decline in the number and activity of cardiac mitochondria, impeding the switch to oxidative metabolism. These alterations to the metabolic program and HIF1 expression in the embryo compromise the contractile capacity of the myocardium and significantly impair heart function." In conclusion, the progressive transition to oxidative metabolism in the embryonic myocardium parallels the gradual loss of HIF1; these changes are necessary for correct maturation and contraction of the muscle and to preserve the genetic program that establishes the cardiac conduction system, permitting the correct formation of the ventricles. In addition to clarifying the direct involvement of HIF1 in the link between metabolic status and myocardial maturation and function, the study "opens the route to new therapeutic interventions" targeting HIF1 or metabolic status to improve cardiac function in cardiovascular diseases.


News Article | November 29, 2016
Site: phys.org

The regulatory function of ISGylation in the secretion of nanovesicles to the external medium. Credit: CNIC A team of scientists at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), led by Prof. Francisco Sánchez-Madrid, has characterized a cell signal that impedes intercellular communication and could play a central role in biomedical strategies such as gene therapy, vaccine design, and immunotherapy. The study, published today in Nature Communications, characterizes a signal that impedes the secretion of nanovesicles called exosomes. Cells secrete exosomes as a means of intercellular communication; however, certain viruses can use exosomes as "Trojan horses" to facilitate their propagation and entry into neighboring cells. The signal, called ISGylation, has in the past been viewed mainly as an antiviral signal, although some studies show that it can also be activated by other stimuli such as a lack of oxygen, aging or cancer. "In these situations, the secretion of exosomes, and therefore communication between cells, can be affected by this modification," explains Dr. Carolina Villarroya. The research team is dedicated to decoding the processes that control exosome secretion and exploring potential biomedical applications. As Dr. Sánchez-Madrid explains, "as well as acting as messengers in intercellular communication, exosomes are potential tools for gene therapy, vaccine design and immunotherapy." Several clinical trials are underway to assess new treatments using this approach. The Nature Communications article describes how an antiviral signal activates the programmed degradation of proteins involved in exosome degradation. According to Villarroya, this signal "marks specific proteins located in endosomes, the place where exosomes are formed. This mark redirects these proteins toward the degradation pathway and impedes exosome secretion." Sánchez-Madrid points out that this newly identified mechanism, through which cells defend themselves against infection by activating the degradation of their own proteins, "could also be exploited by external agents for their propagation." Explore further: Sleep apnea may make lung cancer more deadly More information: Carolina Villarroya-Beltri et al, ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins, Nature Communications (2016). DOI: 10.1038/ncomms13588


Researchers at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), working in collaboration with colleagues at other centers in Spain and abroad, have identified defects in the hearts of progeria patients that appear to be related to an elevated risk of arrhythmias and premature death. The study, published the Proceedings of the National Academy of Sciences (PNAS), shows that these risks are linked to anomalies in the transmission of electrical signals in the hearts of individuals with Hutchinson-Gilford progeria syndrome (HGPS), also known as progeria. Similar findings were observed in a mouse model of this disease studied by the research team. The findings of this study open the way to research into the development of new treatments to correct these characteristic defects associated with progeria. The study could also provide clues about the mechanisms involved in the development of cardiovascular disease during normal aging. Progeria is a very rare genetic disease, estimated to affect fewer than 400 people worldwide. The disease is caused by a mutation in the gene encoding laminin A (LMNA). "The mutation causes an incorrect processing the messenger RNA encoded by the gene, and this results in the production of an anomalous version of the pre-laminin A protein called progerin, which accumulates in the cell nucleus," explains study coordinator Dr. Vicente Andrés. Children presenting progeria symptoms can be diagnosed with a genetic test, but as yet there is no effective treatment for the disease, and patients die in the first two decades of life. The cause of death in progeria is principally related to cardiovascular problems, but according to first author Dr. José Rivera-Torres "there is a great void of knowledge about the mechanism responsible for the anomalies that characterize progeria." The PNAS study shows for the first time that HGPS patients share similar defects with mice lacking the metaloproteinase ZMPSTE24/FACE1, which the team uses as an experimental model of progeria. The patients and mice both progressively develop electrocardiogram anomalies. "The conduction anomalies in the hearts of progeric mice are accompanied by altered expression of the protein connexin 43, and similar alterations are seen in the hearts of HGPS patients," comments Dr. Andrés. Normally, connexin 43 accumulates at gap junctions--structures in the cell membrane that are essential for the correct propagation of electrical impulses from one cardiomyocyte to another. Altered connexin 43 expression is found in many cardiovascular diseases affecting the general population, and is also associated with normal aging. Aberrant connexin 43 expression provokes electrical alterations in the myocardium that favor the development of arrhythmias. The PNAS study shows that in the cardiomyocytes of progeria patients and progeric mice, connexin 43 is incorrectly localized laterally and accumulates in the perinuclear region of the cytoplasm. According to coauthors Drs. José Jalife and David Filgueiras, "these findings open a new chapter in the understanding of the cardiovascular consequences of this disease." For example, the similarities between patients and the mouse model of HGPS suggest that mislocalization of connexin 43 reduces connectivity between cardiomyocytes, thus increasing the risk of arrhythmias and premature death. "To build on these findings, we are now studying why connexin 43 mislocalizes in the hearts of HGPS patients and progeric mice. These studies could also help in the design of therapies to correct the cardiac electrical defects in progeria," says Dr. Andrés. Many of the anomalies of progeria are also characteristics of normal aging, suggesting that shared mechanisms trigger cardiovascular alterations in HGPS patients and the elderly population. Dr. Rivera-Torres comments that, consistent with this idea, other studies have demonstrated the production of prelaminin A and progerin in cells and tissues of individuals unaffected by HGPS. The research team therefore hopes that the study of this rare disease will provide important information about the mechanisms implicated in normal aging and associated heart disease.


News Article | February 28, 2017
Site: www.eurekalert.org

Scientists at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) have identified a possible therapeutic target for 2 types of very aggressive lymphomas. The CNIC team discovered that the microRNA miR-28 regulates the terminal differentiation of B lymphocytes, blocking the growth of B cell lymphomas. The study, published in Blood, establishes the therapeutic potential of synthetic miR-28 analogs for inhibiting the growth of Birkitt lymphoma and diffuse large cell lymphoma. These findings could lead to the development of the first miRNA analog therapy for the treatment of B cell lymphoma and provide the basis for human trials. Most diagnosed lymphomas originate in mature B lymphocytes. An estimated 400 000 people are diagnosed with lymphoma every year, and more than 200 000 people die each year as a consequence of this type of blood cancer. Around 60% of patients have very aggressive forms of the disease, such as Burkitt lymphoma or diffuse large cell lymphoma, and these patients often do not respond to chemotherapy, or their disease relapses after treatment. Because of this, research coordinator Dr. Almudena Ramiro stresses that "we need to find alternative therapies to replace or complement those that are already available." MiroRNAs (miRNAs) are small RNA molecules that regulate gene expression, influencing diverse biological and disease processes. The molecular characteristics and biological versatility of miRNAs has attracted intense interest in their potential in the treatment of cancer. In the Blood article, the CNIC research team characterizes the function of miR-28 in the biology of mature B lymphocytes and in the development of lymphomas associated with this cell type. The results of the study demonstrate that miR-28 regulates the terminal differentiation of B lymphocytes, a fundamental process in the biology of these cells that generates memory B lymphocytes and highly specific plasma cells. According to Dr. Ramiro, "the presence of miR-28 reduces the proliferative capacity and survival of mature B lymphocytes." The research team discovered that miR-28 is often lost in lymphomas, and that re-establishing its expression slows tumor growth. The study authors conclude by emphasizing the importance of identifying drugs that can improve the efficacy and reduce the toxicity of current standard lymphoma treatments. The results of this study reveal the therapeutic potential of miR-28 and provide ample justification for the initiation of clinical trials of miR-28-based therapies to treat B cell lymphomas.

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