Article
Multidisciplinary Sciences
Jeong Hyun Ahn, Eric S. Davis, Timothy A. Daugird, Shuai Zhao, Ivana Yoseli Quiroga, Hidetaka Uryu, Jie Li, Aaron J. Storey, Yi-Hsuan Tsai, Daniel P. Keeley, Samuel G. Mackintosh, Ricky D. Edmondson, Stephanie D. Byrum, Ling Cai, Alan J. Tackett, Deyou Zheng, Wesley R. Legant, Douglas H. Phanstiel, Gang Greg Wang
Summary: The development of cancer is closely associated with genetic abnormalities targeting proteins with intrinsically disordered regions (IDRs), which play a crucial role in leukaemic transformation. The presence of IDRs within chimera transcription factors promotes liquid-liquid phase separation (LLPS), enhancing their genomic targeting and inducing aberrant three-dimensional chromatin structure during tumourous transformation.
Article
Cell Biology
Jun Wang, Xi Liu, Yuanfeng Huang, Pan Li, Minqiang Yang, Shanshan Zeng, Danyang Chen, Qian Wang, Hao Liu, Kai Luo, Jin Deng
Summary: This study found that overexpression of NNMT is associated with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Targeting NNMT may be a potential therapeutic strategy to overcome EGFR TKI resistance.
CELL DEATH DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Yingwei Li, Zhongshao Chen, Jiali Peng, Cunzhong Yuan, Shi Yan, Ning Yang, Peng Li, Beihua Kong
Summary: This study found that SNRPB plays a key role in ovarian cancer and is associated with poor prognosis. Functionally, SNRPB knockdown inhibits ovarian cancer cell proliferation and invasion, while overexpression has the opposite effect. SNRPB expression increases after cisplatin treatment, and silencing SNRPB enhances ovarian cancer cell sensitivity to cisplatin. SNRPB promotes ovarian cancer progression by repressing exon 3 skipping of POLA1 and BRCA2.
Article
Medicine, Research & Experimental
Jane H. C. Loong, Tin-Lok Wong, Man Tong, Rakesh Sharma, Lei Zhou, Kai-Yu Ng, Hua-Jian Yu, Chi-Han Li, Kwa Man, Chung-Mau Lo, Xin-Yuan Guan, Terence K. Lee, Jing-Ping Yun, Stephanie K. Y. Ma
Summary: Glucose restriction promotes cancer stemness by inducing fucosylation, driving drug resistance and tumor recurrence. Inhibiting FUT1 can mitigate tumor growth and drug resistance, and enhance sensitivity to sorafenib in hepatocellular carcinoma patients.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
Sung Kook Chun, Bridget M. Fortin, Rachel C. Fellows, Amber N. Habowski, Amandine Verlande, Wei A. Song, Alisa L. Mahieu, Austin E. Y. T. Lefebvre, Jason N. Sterrenberg, Leandro M. Velez, Michelle A. Digman, Robert A. Edwards, Nicholas R. Pannunzio, Marcus M. Seldin, Marian L. Waterman, Selma Masri
Summary: An alarming rise in young onset colorectal cancer (CRC) has been reported, but the underlying molecular mechanism is unknown. Lifestyle and dietary factors are suspected risk factors for young onset CRC. Clock disruption, both genetically and environmentally, accelerates Apc-driven CRC pathogenesis. Using an intestinal organoid model, researchers show that clock disruption promotes transformation by driving Apc loss of heterozygosity and hyperactivating Wnt signaling.
Article
Multidisciplinary Sciences
Donghai Wang, Zhinang Yin, Honghong Wang, Liyuan Wang, Tianyu Li, Ruijing Xiao, Ting Xie, Ruyi Han, Rui Dong, Hudan Liu, Kaiwei Liang, Guoliang Qing
Summary: MYCN amplification in neuroblastoma leads to aberrant expression of MYCN oncoprotein, which activates active genes and enhances transcriptional elongation. Super elongation complex (SEC) is identified as a vulnerability in MYCN-amplified neuroblastomas and is recruited by MYCN to enhance processive transcription elongation. Inhibition of SEC leads to global reduction in transcription elongation and selective apoptosis of MYCN-amplified neuroblastoma cells, and synergistically enhances the therapeutic efficacy of BCL-2 antagonist ABT-199 in MYCN-amplified neuroblastomas.
Article
Microbiology
Jie Ma, Miao Zhou, Zehe Song, Yuankun Deng, Siting Xia, Yunxia Li, Xingguo Huang, Dingfu Xiao, Yulong Yin, Jie Yin
Summary: This study reveals the association between gut fungi and obesity development. Specific fungal species, Ascomycota_sp. and Microascaceae_sp., were found to be reduced in obese mice and negatively correlated with fat content. Oral supplementation with fungi can prevent and treat diet-induced obesity.
Review
Chemistry, Medicinal
Rasha Irshad, Sazi Tabassum, Mohammad Husain
Summary: It is well-known that cancer cells undergo metabolic reprogramming, especially in lipid metabolism, to support their survival and aggressive behavior. This altered lipid metabolism provides the necessary energy and building blocks for uncontrolled cell proliferation, immune evasion, tumor formation, angiogenesis, metastasis, and invasion. The dysregulation of lipid metabolism has been identified as a potential target for novel anti-cancer therapies and prognostic indicators for various tumor types.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Gang Yuan, Natasha M. Flores, Simone Hausmann, Shane M. Lofgren, Vladlena Kharchenko, Maria Angulo-Ibanez, Deepanwita Sengupta, Xiaoyin Lu, Iwona Czaban, Dulat Azhibek, Silvestre Vicent, Wolfgang Fischle, Mariusz Jaremko, Bingliang Fang, Ignacio I. Wistuba, Katrin F. Chua, Jack A. Roth, John D. Minna, Ning-Yi Shao, Lukasz Jaremko, Pawel K. Mazur, Or Gozani
Summary: Amplification of the chromosomal region 8p11-12 is common in lung squamous cell carcinoma (LUSC) and the NSD3 gene in this region is identified as a key regulator of LUSC tumorigenesis. NSD3 depletion attenuates tumor growth and enhances survival in LUSC, suggesting its potential as a therapeutic target. Additionally, NSD3-dependent LUSC xenografts are sensitive to bromodomain inhibition, indicating a vulnerability of LUSC to this treatment.
Article
Immunology
Xue Liu, Yan Geng, Jiurong Liang, Ana Lucia Coelho, Changfu Yao, Nan Deng, Yizhou Wang, Kristy Dai, Guanling Huang, Ting Xie, Ningshan Liu, Simon C. Rowan, Forough Taghavifar, Vrishika Kulur, Zhenqiu Liu, Barry R. Stripp, Cory M. Hogaboam, Dianhua Jiang, Paul W. Noble
Summary: This study suggests that HER2 signaling may play a crucial role in fibroblast invasion and lung fibrosis in IPF, making it a potential target for therapeutic intervention.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Cell Biology
Xin Peng, Xiaoli Liu, Wanshan Hu, Yanling Zhou, Lianlian Ouyang, Xintong Peng, Yao Long, Jingyue Sun, Tania Tao, Ling Chen, Ying Shi, Yongguang Tao, Desheng Xiao, Shuang Liu
Summary: In lung adenocarcinoma, overexpression of HOXC11 is associated with worse survival and is regulated by IKK alpha. HOXC11 promotes lung cancer progression by enhancing the expression of SPHK1 through directly binding to its promoter region.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Christina M. Bebber, Emily S. Thomas, Jenny Stroh, Zhiyi Chen, Ariadne Androulidaki, Anna Schmitt, Michaela N. Hoehne, Lukas Stueker, Cleidson de Padua Alves, Armin Khonsari, Marcel A. Dammert, Fatma Parmaksiz, Hannah L. Tumbrink, Filippo Beleggia, Martin L. Sos, Jan Riemer, Julie George, Susanne Brodesser, Roman K. Thomas, H. Christian Reinhardt, Silvia von Karstedt
Summary: The loss of TP53 and RB1 in treatment-naive small cell lung cancer (SCLC) indicates a need to inactivate cell death pathways prior to therapy. This study identifies non-neuroendocrine (NE) SCLC as vulnerable to ferroptosis and neuroendocrine (NE) SCLC as susceptible to TRX pathway inhibition, with combining these treatments showing promise in overcoming subtype plasticity in SCLC.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Juan Zhou, Zhao Jing, Su Chunxia
Summary: Cancer stem cells play a critical role in cancer progression, with aberrant lipid metabolism having a significant impact on disease pathogenesis.
CURRENT CANCER DRUG TARGETS
(2021)
Article
Hematology
Johannes Schmoellerl, Ines A. M. Barbosa, Martina Minnich, Florian Andersch, Leonie Smeenk, Marije Havermans, Thomas Eder, Tobias Neumann, Julian Jude, Michaela Fellner, Anja Ebert, Monika Steininger, Ruud Delwel, Florian Grebien, Johannes Zuber
Summary: Chromosomal rearrangements involving the MDS1 and EVI1 complex locus (MECOM) on chromosome 3q26 define an aggressive subtype of acute myeloid leukemia (AML) that is associated with chemotherapy resistance and dismal prognosis. EVI1 controls the expression of ERG and occupies a conserved intragenic enhancer region in AML, and interfering with this regulatory axis may provide entry points for the development of rational targeted therapies.
Article
Medicine, Research & Experimental
Weihao Li, Kai Huang, Fengbiao Wen, Guanghui Cui, Haizhou Guo, Zhanfeng He, Song Zhao
Summary: In this study, we found that miR-320b expression is decreased in lung cancer patients with OSAH. Intermittent hypoxia treatment downregulated miR-320b expression but promoted the proliferation and invasion abilities of lung cancer cells, which were both suppressed by overexpression of miR-320b.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Endocrinology & Metabolism
Samuel Furse, Albert Koulman, Susan E. Ozanne, Lucilla Poston, Sara L. White, Claire L. Meek
Summary: Gestational diabetes in obese women is associated with elevated levels of specific lipids related to de novo lipogenesis, which are also correlated with measures of offspring adiposity. These findings suggest that the effects of GDM on neonatal body composition may not be solely due to hyperglycemia, but may involve other pathways.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Health Care Sciences & Services
Albert Koulman, Kirsten L. Rennie, Damon Parkington, Carina S. B. Tyrrell, Michael Catt, Effrossyni Gkrania-Klotsas, Nicholas J. Wareham
Summary: This study developed a device for blood sample collection at home and applied it in a large-scale remote monitoring study, showing high participant acceptability and high consistency with traditional blood collection methods in results.
JOURNAL OF TELEMEDICINE AND TELECARE
(2022)
Article
Oncology
Denis Seyres, Alessandra Cabassi, John J. Lambourne, Frances Burden, Samantha Farrow, Harriet McKinney, Joana Batista, Carly Kempster, Maik Pietzner, Oliver Slingsby, Thong Huy Cao, Paulene A. Quinn, Luca Stefanucci, Matthew C. Sims, Karola Rehnstrom, Claire L. Adams, Amy Frary, Bekir Erguener, Roman Kreuzhuber, Gabriele Mocciaro, Simona D'Amore, Albert Koulman, Luigi Grassi, Julian L. Griffin, Leong Loke Ng, Adrian Park, David B. Savage, Claudia Langenberg, Christoph Bock, Kate Downes, Nicholas J. Wareham, Michael Allison, Michele Vacca, Paul D. W. Kirk, Mattia Frontini
Summary: This study aims to improve the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature. The results showed that extreme phenotype groups could be distinguished from lean individuals and from each other across all data layers. In addition, the gene expression landscape of the obese group changed after surgical intervention, indicating improvement in specific pathways.
CLINICAL EPIGENETICS
(2022)
Article
Multidisciplinary Sciences
Kerry S. S. Jones, Damon A. A. Parkington, Megan W. W. Bourassa, Carla Cerami, Albert Koulman
Summary: Thiamine (vitamin B1) is an essential micronutrient that plays a crucial role as a cofactor in various metabolic processes. A reliable biomarker for thiamine status is important due to the poorly defined clinical symptoms of thiamine deficiency. This study provides a comprehensive protocol for measuring basal erythrocyte transketolase activity, which can help standardize methods and improve replication between laboratories.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Samuel Furse, Hannah L. Morgan, Albert Koulman, Adam J. Watkins
Summary: There is evidence to suggest that poor paternal diet during conception can increase the risk of offspring developing metabolic diseases later in life. This study found that a low protein-high carbohydrate diet in male mice affected the lipid profiles of their offspring's hearts and brains. These effects were observed from a young age and varied between sexes. These findings highlight the importance of paternal diet in the development of non-communicable diseases in offspring.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Luis Herrera-Marcos, Roberto Martinez-Beamonte, Carmen Arnal, Cristina Barranquero, Juan J. Puente-Lanzarote, Tania Herrero-Continente, Jose M. Lou-Bonafonte, Gonzalo Gonzalo-Romeo, Gabriele Mocciaro, Benjamin Jenkins, Joaquin C. Surra, Maria J. Rodriguez-Yoldi, Juan Carlos Burillo, Roberto Lasheras, Agustin Garcia-Gil, Antonio Guemes, Albert Koulman, Jesus Osada
Summary: This study investigated the effects of squalene on a porcine model of hepatic steatohepatitis and the associated lipidomic changes. The results showed that supplementation of a steatotic diet with 0.5% squalene for one month led to a decrease in hepatic triglyceride content and area of hepatic lipid droplets, without affecting cholesterol content or fiber areas. However, the ballooning score was increased and correlated with hepatic squalene content. Furthermore, squalene supplementation altered the hepatic and plasma lipidomic profiles, as well as the expression of non-coding RNA and the anti-inflammatory interleukin.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hugo J. R. Fernandes, Josh P. P. Kent, Michaela Bruntraeger, Andrew R. R. Bassett, Albert Koulman, Emmanouil Metzakopian, Stuart G. G. Snowden
Summary: The metabolic basis of Parkinson's disease is poorly understood, but it is known that mitochondrial and endoplasmic reticulum stress play a role in the pathology. In this study, the effects of mitochondrial and ER stress on dopamine neuron metabolism were examined, and it was found that both stresses caused significant dysregulation of metabolism, with triglyceride accumulation being a major driver. Understanding the mechanisms of triglyceride accumulation could lead to new therapeutic approaches.
Article
Endocrinology & Metabolism
Anna-Maria Lampousi, Sofia Carlsson, Josefin E. Lofvenborg, Natalia Cabrera-Castro, Maria-Dolores Chirlaque, Guy Fagherazzi, Paul W. Franks, Christiane S. Hampe, Paula Jakszyn, Albert Koulman, Cecilie Kyro, Conchi Moreno-Iribas, Peter M. Nilsson, Salvatore Panico, Keren Papier, Yvonne T. van der Schouw, Matthias B. Schulze, Elisabete Weiderpass, Raul Zamora-Ros, Nita G. Forouhi, Stephen J. Sharp, Olov Rolandsson, Nicholas J. Wareham
Summary: The study found that decreased levels of circulating odd-chain fatty acids (OCFA), particularly 17:0, were associated with an increased incidence of adult-onset diabetes in both GAD65Ab-positive and GAD65Ab-negative individuals. Additionally, the combination of low 17:0 and high GAD65Ab positivity significantly increased the risk of diabetes.
Article
Endocrinology & Metabolism
Sara L. White, Albert Koulman, Susan E. Ozanne, Samuel Furse, Lucilla Poston, Claire L. Meek
Summary: This study investigated whether the patterns of glycaemia during the oral glucose tolerance test (OGTT) in pregnancy could reflect different pathophysiological subtypes of gestational diabetes mellitus (GDM) defined by insulin secretion/sensitivity or lipid profiles. The severity of glucose derangement was strongly associated with insulin action and lipid abundance/profile, suggesting that the patterns of glycemia during the OGTT may contribute to a precision approach to GDM.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Medicine, General & Internal
Jakub G. D. Sobiecki, Fumiaki Imamura, Courtney R. Davis, Stephen J. Sharp, Albert Koulman, Jonathan M. Hodgson, Marcela Guevara, Matthias B. Schulze, Ju-Sheng Zheng, Claudia Agnoli, Catalina Bonet, Sandra M. Colorado-Yohar, Guy Fagherazzi, Paul W. Franks, Thomas E. Gundersen, Franziska Jannasch, Rudolf Kaaks, Verena Katzke, Esther Molina-Montes, Peter M. Nilsson, Domenico Palli, Salvatore Panico, Keren Papier, Olov Rolandsson, Carlotta Sacerdote, Anne Tjonneland, Tammy Y. N. Tong, Yvonne T. van der Schouw, John Danesh, Adam S. Butterworth, Elio Riboli, Karen J. Murphy, Nicholas J. Wareham, Nita G. Forouhi
Summary: A study found that adherence to the Mediterranean diet lowered the risk of type 2 diabetes, and objectively assessed adherence had a stronger association than self-reported adherence. The study used biomarkers to assess the actual effectiveness of the Mediterranean diet and found that higher adherence was associated with lower incidence of type 2 diabetes. This research is of importance in reducing the risk of type 2 diabetes and reducing the burden on the population.
Article
Endocrinology & Metabolism
Claire L. Meek, Zoe A. Stewart, Denice S. Feig, Samuel Furse, Sandra L. Neoh, Albert Koulman, Helen R. Murphy
Summary: This study found that maternal hyperglycemia and offspring hyperinsulinism in women with type 1 diabetes during pregnancy are associated with perinatal complications and suboptimal pregnancy outcomes. Metabolomic analysis revealed distinct metabolite profiles for different complications, such as increased carnitines and lipid metabolites in large for gestational age infants, and changes in triacylglycerols or dietary phenols in neonatal hypoglycemia and offspring hyperinsulinism. Altered lipid metabolism is a key feature in type 1 diabetes pregnancy, suggesting the need for new strategies to optimize maternal diet and insulin dosing from the first trimester.
Article
Endocrinology & Metabolism
Jane L. Tarry-Adkins, India G. Robinson, Lucas C. Pantaleao, Jenna L. Armstrong, Benjamin D. Thackray, Lorenz M. W. Holzner, Alice E. Knapton, Sam Virtue, Benjamin Jenkins, Albert Koulman, Andrew J. Murray, Susan E. Ozanne, Catherine E. Aiken
Summary: This study found that metformin use during pregnancy may decrease oxidative phosphorylation in the placenta and result in lipid accumulation, particularly of polyunsaturated fatty acids, in trophoblast cells. These findings are clinically important for evaluating the balance of risks and benefits associated with metformin use during pregnancy.
Article
Nutrition & Dietetics
Andrea Soria-Gondek, Pablo Fernandez-Garcia, Lorena Gonzalez, Marjorie Reyes-Farias, Marta Murillo, Aina Valls, Nativitat Real, Silvia Pellitero, Jordi Tarasco, Benjamin Jenkins, Maria Galan, Francesc Villarroya, Albert Koulman, Patricia Corrales, Antonio Vidal-Puig, Ruben Cereijo, David Sanchez-Infantes
Summary: The objective of this study was to assess the circulating lipidome of children and adults with obesity before and after clinical interventions. The findings showed that certain lipid species increased in abundance in both children and adults, while others decreased. There was a specific set of lipid species that were regulated after clinical interventions in both age groups, suggesting a core circulating lipid profile indicative of obesity development and improvement.
Meeting Abstract
Gastroenterology & Hepatology
Gabriele Mocciaro, Michael Allison, Benjamin Jenkins, Vian Azzu, Isabel Huang-Doran, Richard Kay, Antonio Murgia, Davies Susan, Mattia Frontini, Antonio Vidal-Puig, Albert Koulman, Julian L. Griffin, Michele Vacca
JOURNAL OF HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Christian A. Hudert, Leon A. Adams, Anna Alisi, Quentin M. Anstee, Annalisa Crudele, Laura G. Draijer, Samuel Furse, Jan G. Hengstler, Benjamin Jenkins, Kylie Karnebeek, Deirdre A. Kelly, Bart G. Koot, Albert Koulman, David Meierhofer, Phillip E. Melton, Trevor A. Mori, Stuart G. Snowden, Indra van Mourik, Anita Vreugdenhil, Susanna Wiegand, Jake P. Mann
Summary: Genome-wide association studies have identified variants in HSD17B13 and MTARC1 genes that are associated with less severe pediatric NAFLD. Metabolomics studies showed that these variants were associated with reduced liver inflammation and steatosis. These findings provide further evidence for shared genetic mechanisms between pediatric and adult NAFLD.
HEPATOLOGY COMMUNICATIONS
(2022)