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5-Methyluridine is Ubiquitous in Pseudomonas aeruginosa tRNA and Modulates Antimicrobial Resistance and Virulence

Journal of Molecular Biology 2025年 169020页

作者： Chittrakanwong, Jurairat Chen, Ruixi Wu, Junzhou Demott, Michael S. Sun, Jingjing Phatinuwat, Kamonwan Jaroensuk, Juthamas Atichartpongkul, Sopapan Mongkolsuk, Skorn Begley, Thomas Dedon, Peter C. Fuangthong, Mayuree Program in Applied Biological Sciences Chulabhorn Graduate Institute Bangkok Thailand Department of Biological Engineering Massachusetts Institute of Technology Cambridge MA United States Antimicrobial Resistance Interdisciplinary Research Group Singapore-MIT Alliance for Research and Technology Singapore Singapore Center for Environmental Health Sciences Massachusetts Institute of Technology Cambridge MA United States Laboratory of Biotechnology Chulabhorn Research Institute Bangkok Thailand Center of Excellence on Environmental Health and Toxicology (EHT) Bangkok Thailand The RNA Institute and Department of Biological Sciences University at Albany Albany NY United States

Building on decades of work in characterizing the dozens of RNA modifications in the microbial epitranscriptome, recent advances in analytical technology and genetics have revealed systems-level functions for many tRNA modifications. The tRNA (uracil-5-)-methyltransferase TrmA and its product, 5-methyl uridine (m⁵U) at position 54 in the T-loop, however, has not been linked to a specific phenotype. Here, we defined the functional and biological roles of TrmA in Pseudomonas aeruginosa (PA14), a major multidrug-resistant pathogen. Surprisingly, though TrmA was found to site-specifically catalyze m⁵U54 on all PA14 tRNAs, loss of TrmA had no effect on the levels of any of 36 tRNA modifications except m⁵U and had minimal effects on multiple phenotypic parameters, including growth rate, morphology, motility, and biofilm formation. However, loss of TrmA conferred a striking polymyxin antibiotic resistance. mRNA and tRNA profiling and proteomics analyses revealed that TrmA regulates the expression of codon-biased gene families at the level of translation, including components of a type III secretion system (T3SS). Loss of TrmA upregulated T3SS, leading to increased macrophage IL-1β in bacterial challenge tests. Altogether, these results revealed novel biological functions of TrmA and its roles in modulating gene expression at multiple levels in P. aeruginosa. © 2025 Elsevier Ltd

关键词： codon usage Pseudomonas aeruginosa translation TrmA tRNA modification

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Changing life expectancy in European countries 1990–2021: a subanalysis of causes and risk factors from the Global Burden of Disease Study 2021

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The Lancet Public health 2025年第3期10卷 e172-e188页

作者： Steel, Nicholas Bauer-Staeb, Clarissa Maria Mercedes Ford, John A. Abbafati, Cristiana Abdalla, Mohammed Altigani Abdelkader, Atef Abdi, Parsa Zuñiga, Roberto Ariel Abeldaño Abiodun, Olugbenga Olusola Abolhassani, Hassan Abu-Gharbieh, Eman Abukhadijah, Hana J. Abu-Zaid, Ahmed Addo, Isaac Yeboah Addolorato, Giovanni Adekanmbi, Victor Adetunji, Juliana Bunmi Adeyeoluwa, Temitayo Esther Agardh, Emilie E. Agyemang-Duah, Williams Ahmad, Danish Ahmed, Ayman Ahmed, Syed Anees Akinosoglou, Karolina Akkaif, Mohammed Ahmed Al Awaidy, Salah Al Hasan, Syed Mahfuz Al Zaabi, Omar Ali Mohammed Aldridge, Robert W. Algammal, Abdelazeem M. Al-Gheethi, Adel Ali Saeed Ali, Abid Ali, Mohammed Usman Ali, Syed Shujait Ali, Waad Alicandro, Gianfranco Alif, Sheikh Mohammad Al-Jumaily, Adel Allebeck, Peter Alrawashdeh, Ahmad Al-Rifai, Rami H. Alsabri, Mohammed A. Alshahrani, Najim Z. Aluh, Deborah Oyine Al-Wardat, Mohammad Al-Zyoud, Walid A. Amiri, Sohrab Anderlini, Deanna Andrei, Catalina Liliana Anil, Abhishek Anvari, Saeid Anyasodor, Anayochukwu Edward Appiah, Seth Christopher Yaw Aquilano, Michele Arabloo, Jalal Arafat, Mosab Areda, Demelash Aremu, Abdulfatai Armani, Keivan Armocida, Benedetta Ärnlöv, Johan Asaduzzaman, Muhammad Astell-Burt, Thomas Aujayeb, Avinash Ausloos, Marcel Azadnajafabad, Sina Aziz, Shahkaar Azzam, Ahmed Y. Babu, Giridhara Rathnaiah Badache, Andreea Corina Badiye, Ashish D. Bahramian, Saeed Baig, Atif Amin Baker, Jennifer L. Bansal, Hansi Bärnighausen, Till Winfried Barone, Mark Thomaz Ugliara Barrow, Amadou Barteit, Sandra Bashir, Shahid Bashiru, Hameed Akande Basso, João Diogo Bastan, Mohammad-Mahdi Basu, Sanjay Batra, Kavita Bauckneht, Matteo Baune, Bernhard T. Beghi, Massimiliano Beiranvand, Maryam Béjot, Yannick Bell, Michelle L. Bello, Olorunjuwon Omolaja Belo, Luis Beloukas, Apostolos Beneke, Alice A. Bettencourt, Paulo J.G. Bhagavathula, Akshaya Srikanth Bhala, Neeraj Bhaskar, Sonu Bisulli, Francesca Bjørge, Tone Bodunrin, Aadam Olalekan Carvajal, Alejandro Botero Bouaoud, Souad Brayne, Carol Brenner, H Department of Primary Care and Public Health University of East Anglia Norwich United Kingdom Office for Health Improvement and Disparities Department of Health and Social Care London United Kingdom Department of Legal and Economic Studies La Sapienza University Rome Italy Rome Italy Hull York Medical School University of Hull Hull United Kingdom Department of Mathematics and Sciences Ajman University Ajman United Arab Emirates Department of Medicine Memorial University St. John's NL Canada Postgraduate Department University of Sierra Sur Miahuatlan de Porfirio Diaz Mexico Yhteiskuntadatatieteen keskus (Centre for Social Data Science) Helsinki Finland Department of Internal Medicine Federal Medical Centre Abuja Nigeria Research Center for Immunodeficiencies Tehran University of Medical Sciences Tehran Iran Department of Medical Biochemistry and Biophysics Karolinska Institutet (Karolinska Institute) Stockholm Sweden Department of Clinical Sciences University of Sharjah Sharjah United Arab Emirates Department of Biopharmaceutics and Clinical Pharmacy University of Jordan Amman Jordan Medical Research Center Hamad Medical Corporation Doha Qatar Department of Biochemistry and Molecular Medicine Alfaisal University Riyadh Saudi Arabia College of Graduate Health Sciences University of Tennessee Memphis TN United States School of Medicine Sydney NSW Australia Centre for Social Research in Health University of New South Wales Sydney NSW Australia Internal Medicine and Alcohol Related Disease Unit Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy Department of Medical and Surgical Sciences Università Cattolica di Roma (Catholic University of Rome) Rome Italy Department of Obstetrics and Gynecology University of Texas Medical Branch Galveston TX United States Department of Biochemistry Osun State University Osogbo Nigeria Department of Pharmacology and Therapeutics University of Medical Sciences Ondo Ondo Nigeria Department of Veteri

Background: Decades of steady improvements in life expectancy in Europe slowed down from around 2011, well before the COVID-19 pandemic, for reasons which remain disputed. We aimed to assess how changes in risk factors and cause-specific death rates in different European countries related to changes in life expectancy in those countries before and during the COVID-19 pandemic. Methods: We used data and methods from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to compare changes in life expectancy at birth, causes of death, and population exposure to risk factors in 16 European Economic Area countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, and Sweden) and the four UK nations (England, Northern Ireland, Scotland, and Wales) for three time periods: 1990–2011, 2011–19, and 2019–21. Changes in life expectancy and causes of death were estimated with an established life expectancy cause-specific decomposition method, and compared with summary exposure values of risk factors for the major causes of death influencing life expectancy. Findings: All countries showed mean annual improvements in life expectancy in both 1990–2011 (overall mean 0·23 years [95% uncertainty interval [UI] 0·23 to 0·24]) and 2011–19 (overall mean 0·15 years [0·13 to 0·16]). The rate of improvement was lower in 2011–19 than in 1990–2011 in all countries except for Norway, where the mean annual increase in life expectancy rose from 0·21 years (95% UI 0·20 to 0·22) in 1990–2011 to 0·23 years (0·21 to 0·26) in 2011–19 (difference of 0·03 years). In other countries, the difference in mean annual improvement between these periods ranged from –0·01 years in Iceland (0·19 years [95% UI 0·16 to 0·21] vs 0·18 years [0·09 to 0·26]), to –0·18 years in England (0·25 years [0·24 to 0·25] vs 0·07 years [0·06 to 0·08]). In 2019–21, there was an overall decrease in mean annual life expectancy a

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Phase Ⅰ of cardiac rehabilitation:A new challenge for evidence based physiotherapy

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World Journal of Cardiology 2011年第7期3卷 248-255页

作者： Rafael Michel de Macedo JoséRocha Faria-Neto Costantino Ortiz Costantini Dayane Casali Andrea Pires Muller Costantino Roberto Costantini Katherine Athayde Teixeira de Carvalho Luiz César Guarita-Souza Department of Rehabilitation Costantini Cardiological HospitalCuritiba80320-320Brazil Graduate Program in Health Sciences Catholic Pontificia University of ParanáCuritiba80215-901Brazil Graduate Program in Biotechnology Applied to Health Pequeno Príncipe FacultyCuritiba80230-020Brazil

Cardiac rehabilitation protocols applied during the inhospital phase(phaseⅠ)are subjective and their results are contested when evaluated considering what should be the three basic principles of exercise prescription:specificity,overload and *** this review,we focus on the problems associated with the models of exercise prescription applied at this early stage in-hospital and adopted today,especially the lack of clinical studies demonstrating its ***,we present the concept of"periodization"as a useful tool in the search for better results.

关键词： Cardiac rehabilitation Exercise physiology Physical therapy

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DSG2 attenuates gemcitabine efficacy through PTX3 in lung adenocarcinoma

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Biochimica et Biophysica Acta - Molecular Basis of Disease 2025年第6期1871卷 167881页

作者： Wang, Chin-Chou Lin, Jo-Ying Wang, Chih-Yang Shen, Wan-Jou Liao, Pin-Chen Ho, Yu-Fang Lin, Che-Wei Wang, Shao-An Ko, Ching-Chung Dey, Sanskriti Ta, Hoang Dang Khoa Xuan, Do Thi Minh Kumar, Sachin William, Bianca Tobias Wang, Ju-Ming Wang, Wei-Jan Divisions of Pulmonary and Critical Care Medicine Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan Department of Respiratory Therapy Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan Department of Internal Medicine Kaohsiung Municipal Ta-Tung Hospital Kaohsiung Taiwan Department of Biological Science and Technology China Medical University Taichung 40676 Taiwan Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei 11031 Taiwan TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei 11031 Taiwan Graduate Institute of Biomedical Sciences College of Medicine China Medical University Taichung 40402 Taiwan Department of Medical Imaging Chi-Mei Medical Center Tainan Taiwan Department of Health and Nutrition Chia Nan University of Pharmacy and Science Tainan Taiwan School of Medicine College of Medicine National Sun Yat-Sen University Kaohsiung Taiwan Faculty of Pharmacy Van Lang University 69/68 Dang Thuy Tram Street Ward 13 Binh Thanh District Ho Chi Minh City 70000 Viet Nam Faculty of Biotechnology and Applied Sciences Shoolini University of Biotechnology and Management Sciences Himachal Pradesh India Department of Biomedicine School of Life Sciences Indonesia International Institute for Life Sciences Jl Pulomas Barat Kav 88 Jakarta Timur 13210 Indonesia Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Me

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, often diagnosed at an advanced stage with poor prognosis and limited treatment options. The Desmoglein (DSG) family plays a crucial role in maintaining cell adhesion and tissue integrity. Upregulation of DSG proteins has been implicated in tumorigenesis, invasion, and metastasis across various cancers. However, the role of DSG in lung cancer, particularly as a biomarker influencing the efficacy of anti-cancer drugs, remains unclear. In this study, DSG2 was significantly overexpressed in LUAD tumor tissues and correlated with poor prognosis, as revealed by TCGA database analysis. Additionally, analyses of single-cell sequencing, KEGG, and GSEA multi-omics databases demonstrated that DSG2 modulates multiple oncogenic pathways, particularly the apoptosis pathway, with a strong positive correlation between DSG2 and PTX3 expression. In vitro experiments showed that DSG2 knockdown enhanced gemcitabine-induced apoptosis by downregulating the NFκB/STAT3/PTX3 signaling axis. Furthermore, adding recombinant PTX3 protein in DSG2 knockdown cells restored STAT3 activation, reducing gemcitabine efficacy, indicating that DSG2 contributes to gemcitabine resistance through PTX3-mediated mechanisms. This study identifies DSG2 as a critical mediator of gemcitabine resistance in LUAD through its regulation of the PTX3/NFκB/STAT3 pathway. The findings suggest that targeting DSG2 could enhance the therapeutic efficacy of gemcitabine in LUAD patients, offering a novel therapeutic strategy and biomarker for overcoming chemoresistance in this aggressive cancer subtype. © 2025 Elsevier B.V.

关键词： DSG2 Gemcitabine resistance Lung adenocarcinoma NFκB PTX3

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Risk factors for the development of peripherally inserted central catheter-related bloodstream infection in neonates: Prospective cohort study

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Journal of Neonatal Nursing 2023年第2期29卷 387-392页

作者： Sarmento Diniz, Edienne Rosângela Dantas de Araújo Santos Camargo, Juliana Santos de Medeiros, Kleyton Rosendo da Silva, Richardson Augusto Cobucci, Ricardo Ney Roncalli, Angelo Giuseppe Postgraduate Program in Public Health Federal University of Rio Grande do Norte - UFRN Natal Brazil Maternity School Januário Cicco (MEJC/EBSERH) Federal University of Rio Grande do Norte-UFRN Natal Brazil Instituto de Ensino Pesquisa e Extensão Liga Contra o Câncer Natal Brazil Postgraduate Program in Sciences Applied to Women's Health Januário Cicco Maternity School (MEJC/EBSERH) Federal University of Rio Grande do Norte-UFRN Natal Brazil Biotechnology Graduate Program Potiguar University-UnP Natal Brazil

This study aimed to analyze the factors associated with catheter-related bloodstream infection (CRBSI) in newborns undergoing infusion therapy using a peripherally inserted central catheter (PICC). A prospective cohort of 281 newborns who underwent installation of 483 PICCs in a neonatal intensive care unit (NICU) was followed from catheter insertion until 72 h after removal. Risk factors were assessed by analyzing the association between variables using the chi-square test and relative risk (RR) using the Poisson regression model. The significance level was 5%. Most of the patients were preterm infants with inadequate weight, respiratory disorders, and heart disease, but these variables were not associated with CRBSI. There was a significant association between CRBSI and PICC insertion in the upper limbs of newborns who received infusion therapy in the NICU (RR = 2.84;95% confidence interval 1.02–6.85). © 2022

关键词： Catheter-related infections Catheterization Newborns Peripheral Peripherally inserted central catheter Risk factors

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Bioindustry ethics /

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2005年

作者： David L. Finegold ... [et al.].

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Endophytic fungi of Brunfelsia uniflora: Isolation, cryopreservation, and determination of enzymatic and antioxidant activity

Research Square

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Research Square 2021年

作者： Marsola, Sara Jane Jorge, Lais Freitas Meniqueti, Adriano Borges Bertéli, Miria Benetati Delgado de Lima, Thaís Emanuelle Feijó Bezerra, José Luiz Lopes, Ana Daniela Gazim, Zilda Cristiani do Valle, Juliana Silveira Colauto, Nelson Barros Linde, Giani Andrea Universidade Paranaense Graduate Program of Biotechnology Applied to Agriculture Umuarama87502-210 Brazil Universidade Federal do Recôncavo da Bahia Cruz das Almas44380-00 Brazil Federal University of Bahia Ondina Campus Graduate Program in Food Science - Faculty of Pharmacy Salvador40110-115 Brazil Federal University of Bahia Canela Campus Graduate Program in Food Nutrition and Health - School of Nutrition Salvador40110-907 Brazil

Brunfelsia uniflora (Pohl.) D. Don (Solanaceae), commonly known as manacá-de-cheiro, is widely distributed in Brazil and used by local indigenous peoples as an antirheumatic, antisyphilitic, depurative, emetic, vermifuge, and purgative agent. Several studies have examined the biological activities and phytochemical profile of Brunfelsia;however, few have focused on the diversity of endophytic microorganisms that colonize members of the genus. This study aimed to isolate and cryopreserve endophytic fungi from B. uniflora and determine their cellulase, laccase, and antioxidant activities. Endophytic fungi were isolated from B. uniflora stems, cultured on wheat grains, immersed in a 150 g·L-1 aqueous sucrose solution, and cryopreserved at −80°C for 1 and 6 months. Cellulase activity was determined by a qualitative test using carboxymethylcellulose medium and laccase activity by a quantitative test based on the oxidation of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate). Prior to antioxidant activity assays, fungi were grown in malt extract broth for production of mycelial biomass. A methanolic extract was prepared for evaluation of DPPH• scavenging activity, FRAP activity, and total phenolic content. A total of 46 endophytic fungal isolates were obtained from B. uniflora stems and classified into 24 groups according to morphological similarities. B. uniflora was shown to harbor a great diversity of endophytic fungi. Mycelial viability was observed after 1 and 6 months of cryopreservation at −80 °C. Fungi exhibited cellulase and laccase activities. Isolate CE23 had the highest laccase activity after 7 days of cultivation. Twelve isolates were found to have low total phenolic contents and DPPH• and FRAP activities. © 2021, CC BY.

关键词： Enzymes

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Characterising acute and chronic care needs: insights from the Global Burden of Disease Study 2019

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Nature communications 2025年第1期16卷 4235-4235页

作者： Cecilia Anza-Ramirez J. Jaime Miranda Benedetta Armocida Jorge César Correia Harriette Gillian Christine Van Spall David Beran Amirali Aali Kalkidan Hassen Abate Semagn Mekonnen Abate Cristiana Abbafati Mohsen Abbasi-Kangevari Zeinab Abbasi-Kangevari Zahra Aryan Sina Azadnajafabad Mohammadreza Azangou-Khyavy Seyyed-Hadi Ghamari Mohammad Keykhaei Javad Khanali Sara Momtazmanesh Fateme Montazeri Shayan Rahmani Mohammad-Mahdi Rashidi Nazila Rezaei Negar Rezaei Sahar Saeedi Moghaddam Hossein Hassanian-Moghaddam Ali-Asghar Kolahi Ali Nikoobar Hedayat Abbastabar Ahmed M. Abdel-Azeem Michael Abdelmasseh Juan Sanabria Sherief Abd-Elsalam Ahmed Abdelwahab Gholamreza Abdoli Mohammad Abdollahi Meriem Abdoun Deldar Morad Abdulah Abu Yousuf Md Abdullah Ame Mehadi Abdurehman Getachew Abebe Aidin Abedi Chirag P. Doshi Vida Abedi Hassan Abidi Richard Gyan Aboagye Hassan Abolhassani Nima Rezaei Lucas Guimarães Abreu Michael R. M. Abrigo Yonas Derso Abtew Hiwa Abubaker Ali Eman Abu-Gharbieh Hiba Jawdat Barqawi Rabih Halwani Maha Mohamed Saber-Ayad Iman M. Talaat Ahmed Abu-Zaid Manfred Mario Kokou Accrombessi Juan Manuel Acuna Denberu Eshetie Adane Tigist Demssew Adane Isaac Yeboah Addo Giovanni Addolorato Oluwafemi Atanda Adeagbo Victor Adekanmbi Miracle Ayomikun Adesina Isaac Iyinoluwa Olufadewa Olatunji O. Adetokunboh Daniel Adedayo Adeyinka Qorinah Estiningtyas Sakilah Adnani Aanuoluwapo Adeyimika Afolabi Olayinka Stephen Ilesanmi Muhammad Sohail Afzal Saira Afzal Gina Agarwal Prerna Agarwal Pradyumna Agasthi Anurag Agrawal Marcela Agudelo-Botero Adolfo Martinez-Valle Bright Opoku Ahinkorah Aqeel Ahmad Sajjad Ahmad Sohail Ahmad Tauseef Ahmad Ali Ahmadi Siamak Sabour Keivan Ahmadi Sanjay Basu Sepideh Ahmadi Ali Ahmed Shaun Wen Huey Lee Ayman Ahmed Haroon Ahmed Jivan Qasim Ahmed Gahin Abdulraheem Tayib Yahya Yahya Luai A. Ahmed Iffat Elbarazi Syed Mahboob Shah Janardhana P. Aithala Marjan Ajami Budi Aji Hossein Akbarialiabad Yibeltal Akelew Meisam Akhlaghdoust Elham Jamshidi Addis Aklilu Azene Tesfaye Melat Woldemariam Maxwell Ak CRONICAS Center of Excellence in Chronic Diseases Universidad Peruana Cayetano Heredia Lima Peru School of Medicine Universidad Peruana Cayetano Heredia Lima Peru Sydney School of Public Health Faculty of Medicine and Health University of Sydney Sydney NSW Australia Faculty of Epidemiology and Population Health London School of Hygiene & Tropical Medicine London UK Division of Tropical and Humanitarian Medicine University of Geneva Geneva Switzerland Department of Cardiovascular Endocrine-metabolic Diseases and Aging Istituto Superiore di Sanità Rome Italy Division of Endocrinology Diabetology Nutrition and Therapeutic Patient Education Department of Medicine Geneva University Hospitals Geneva Switzerland Department of Medicine and Department of Health Research Evidence and Impact McMaster University Hamilton ON Canada Research Institute of St. Joe’s Hamilton ON Canada Population Health Research Institute Hamilton Canada Geneva University Hospitals Geneva Switzerland Faculty of Medicine Mashhad University of Medical Sciences Mashhad Iran Department of Nutrition and Dietetics Jimma University Jimma Ethiopia Anesthesiology Department Dilla University Addis Ababa Ethiopia Department of Juridical and Economic Studies La Sapienza University Rome Italy Non-Communicable Diseases Research Center Tehran University of Medical Sciences Tehran Iran Social Determinants of Health Research Center Shahid Beheshti University of Medical Sciences Tehran Iran Brigham and Women’s Hospital Harvard University Boston MA USA Students’ Scientific Research Center (SSRC) Tehran University of Medical Sciences Tehran Iran School of Medicine Tehran University of Medical Sciences Tehran Iran School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran Endocrinology and Metabolism Research Institute Tehran University of Medical Sciences Tehran Iran Chapter of Addiction Medicine University of Sydney Sydney NSW Australia Advanced Diagnostic and Intervent

Chronic care manages long-term, progressive conditions, while acute care addresses short-term conditions. Chronic conditions increasingly strain health systems, which are often unprepared for these demands. This study examines the burden of conditions requiring acute versus chronic care, including sequelae. Conditions and sequelae from the Global Burden of Diseases Study 2019 were classified into acute or chronic care categories. Data were analysed by age, sex, and socio-demographic index, presenting total numbers and contributions to burden metrics such as Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLD), and Years of Life Lost (YLL). Approximately 68% of DALYs were attributed to chronic care, while 27% were due to acute care. Chronic care needs increased with age, representing 86% of YLDs and 71% of YLLs, and accounting for 93% of YLDs from sequelae. These findings highlight that chronic care needs far exceed acute care needs globally, necessitating health systems to adapt accordingly. © 2025. The Author(s).

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BRD4uclear PD-L1/RelB circuit is involved in the stemness of breast cancer cells

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Cell Communication and Signaling 2023年第1期21卷 1-21页

作者： Kim, Su-Lim Choi, Hack Sun Lee, Dong-Sun Bio-Health Materials Core-Facility Center Jeju National University Jeju Republic of Korea Graduate Program for Bio-health/Innovative Drug Development using Subtropical Bio-Resources Jeju National University Jeju Republic of Korea Subtropical/Tropical Organism Gene Bank Jeju National University Jeju Republic of Korea Faculty of Biotechnology College of Applied Life Sciences Jeju National University SARI Jeju Republic of Korea

Breast cancer (BC) is the most common cancer diagnosed in women worldwide. BC stem cells (BCSCs) have been known to be involved in the carcinogenesis of the breast and contribute to therapeutic resistance. The programmed death-ligand 1 (PD-L1) expression of BC correlated with a poor prognosis. Immunotherapies that target PD-L1 have great potential and have been successful when applied to cancer treatment. However, whether PD-L1 regulates BCSC formation is unknown. BCSCs were enriched by serum-free suspension culture. The properties of BCSCs were examined by mammosphere formation assay, CD44+/Cd24−, aldehyde dehydrogenase (ALDH) assay, CSC marker analysis, and mammosphere growth assay. To elucidate the functions of bromodomain-containing protein 4 (BRD4), nuclear PD-L1, and RelB proteins in the stemness of BCSCs, mammosphere formation was examined using BRD4 inhibitor and degrader, PD-L1 degrader, and RelB inhibitor. The antitumor function of 3',4',7,8-tetrahydroxyflavone (THF), a specific BRD4 inhibitor, was studied through in vivo tumor model and mouse studies, and the protein levels of c-Myc, PD-L1, and RelB were examined in tumor model under THF treatment. BRD4 was upregulated in breast CSCs and regulates the stemness of BCs. The downregulation of BRD4 using BRD4 PROTAC, ARV-825, and BRD4 inhibitor, (+)-JQ1, inhibits mammosphere formation and reduces the levels of breast CSC markers (CD44+/CD24− and ALDH1), stem cell marker genes, and mammosphere growth. BRD4 inhibitor (JQ1) and degrader (ARV825) downregulate membrane and nuclear fractions of PD-L1 through the inhibition of PD-L1 transcript levels. The knockdown of PD-L1 inhibits mammosphere formation. Verteporfin, a PD-L1 degrader, inhibits the transcripts and protein levels of PD-L1 and downregulates the transcript and protein levels of RelB. Calcitriol, a RelB inhibitor, and the knockdown of RelB using si-RelB regulate mammosphere formation through interleukin-6 (IL-6) expression. THF is a natural product and

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Comparative modeling of DNA and RNA polymerases from Moniliophthora perniciosa mitochondrial plasmid

Comparative modeling of DNA and RNA polymerases from Monilio...

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2008 International Conference on Bioinformatics, Computational Biology, Genomics and Chemoinformatics, BCBGC 2008

作者： Andrade, Bruno S. Taranto, Alex G. Röessle, Shaila C.S. Góes-Neto, Aristóteles Avery, Mitchell A. Department of Biological Sciences State University of Feira de Santana Graduate Program in Biotechnology Av. Universitária s/n CEP: 44031-460 Feira de Santana - Bahia Brazil Department of Health Sciences State University of Feira de Santana Feira de Santana - Bahia Brazil Av. Universitária s/n CEP: 44031-460 Feira de Santana - Bahia Brazil Bayerischen Akademie der Wissenschaften Boltzmannstraße 1D 85748 Garching bei München Germany Department of Medicinal Chemistry School of Pharmacy Laboratory for Applied Drug Design and Synthesis University MS 38677-1848 United States

ISBN: (纸本)9781615677153

The filamentous fungus Moniliophthora perniciosa (Stahel) Aime & Phillips-Mora is a hemibiotrophic Basidiomycota that causes witches' broom disease of cocoa (Theobroma cacao L.). This disease has resulted in a severe decrease in the Brazilian cocoa production, which changed the position of Brazil in the market from the second largest cocoa exporter to a cocoa importer. Fungal mitochondrial plasmids are usually invertrons encoding DNA and RNA polymerases. Plasmid insertion into host mitochondrial genomes are probably associated to modifications in host generation time, which can be involved in fungal aging. This association suggests activity of polymerases, and these can be used as new targets for drugs against mitochondrial activity of fungi, more specifically against witches' broom disease. DNA and RNA polymerases of M. perniciosa mitochondrial plasmid were completely sequenced and their models were built by Comparative Modeling approach using Swiss-PdbViewer. The DNA and RNA polymerases models were refined by a set of Molecular Mechanics (MM) and Molecular Dynamics (MD) simulation in water. The resultant models were evaluated by Procheck 3.0 and ANOLEA. Ramachandran plots showed 97% and 98% of residues in favorable region for DNA and RNA polymerases, respectively. Potential Energy plots showed, in general, that all atoms of sidechain had favorable thermodynamic values for both proteins. This study can contribute for the development of new alternatives for controlling the fungal agent of witches' broom disease.

关键词： DNA

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