Article
Biochemistry & Molecular Biology
Tao Long, Yang Liu, Xiaochun Li
Summary: Research on ACAT2 structure reveals similar membrane topology to ACAT1, with a cholesterol entry site and an activation site; Mutations in these entry or activation sites were found to attenuate ACAT2 activity, providing insights for designing new inhibitors for cardiovascular disease prevention.
Article
Cell Biology
Robert V. V. Farese, Tobias C. C. Walther
Summary: More than 60 years ago, the pathways of glycerolipid synthesis in the endoplasmic reticulum (ER) were elucidated, but the molecular basis for most of these reactions remained unknown. Recent progress in cell biology, biochemistry, and structural biology has provided a more mechanistic understanding of this pathway. This review provides an overview of molecular aspects of glycerolipid synthesis, focusing on the synthesis of triacylglycerols (TGs), and discusses the mechanisms for storage of TG in cytosolic lipid droplets and the implications for ER stress and cellular toxicity.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2023)
Article
Infectious Diseases
Marina Amaral Xavier, Flavia Roberta Brust, Jessica Waldman, Alexandre Jose Macedo, Maria Aparecida Juliano, Itabajara da Silva Vaz, Carlos Termignoni
Summary: This study suggests that ticks obtain cholesterol from blood meals and interfering with cholesterol metabolism can impair tick reproductive ability and egg development, proposing enzymes and other proteins involved in cholesterol metabolism as potential targets for tick control methods.
TICKS AND TICK-BORNE DISEASES
(2021)
Article
Multidisciplinary Sciences
Fangjun Yu, Zhigang Wang, Tianpeng Zhang, Xun Chen, Haiman Xu, Fei Wang, Lianxia Guo, Min Chen, Kaisheng Liu, Baojian Wu
Summary: The intestinal circadian clock functions as an accelerator in dietary fat absorption, protecting against obesity and related abnormalities induced by a high-fat diet. Targeting intestinal BMAL1 to regulate dietary fat absorption may be a promising approach for managing metabolic diseases caused by excess fat intake.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Keshav Thapa, James J. Kadiri, Karla Saukkonen, Iida Pennanen, Bishwa Ghimire, Minying Cai, Eriika Savontaus, Petteri Rinne
Summary: This study found that Melanocortin 1 receptor (MC1-R) plays a role in regulating cholesterol and bile acid metabolism in the liver, beyond its known functions in skin pigmentation and inflammation. This discovery is important for understanding liver diseases and metabolic disorders.
Article
Chemistry, Medicinal
Pinaki Bhattacharjee, Nicholas Rutland, Malliga R. Iyer
Summary: This article summarizes the literature on various SOAT inhibitory agents and discusses the design, structural requirements, and mode of action of SOAT inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
Jin Li, Hui Wang, Jingbo Xu, Shengyue Wu, Mengmeng Han, Jianfei Li, Qianqian Wang, Zhiming Ge
Summary: A dual-sensitive d-d-rHDL was synthesized and characterized for efficient tumor-targeted drug delivery, using a pH-sensitive BCC as a cholesterol substitute and BSA as a targeting agent. The d-d-rHDL demonstrated superior drug release performance and sensitivity in vitro and in vivo, indicating potential for effective inhibition of tumor growth.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Chemistry, Medicinal
Huji Turdi, Hannguang Chao, Jon J. Hangeland, Saleem Ahmad, Wei Meng, Robert Brigance, Guohua Zhao, Wei Wang, Fang Moore, Xiang-Yang Ye, Arvind Mathur, Xiaoping Hou, James Kempson, Dauh-Rurng Wu, Yi-Xin Li, Anthony Azzara, Zhengping Ma, Ching-Hsuen Chu, Luping Chen, Mary Jane Cullen, Suzanne Rooney, Susan Harvey, Lisa Kopcho, Reshma Panemangelor, Lynn Abell, Kevin O'Malley, William J. Keim, Elizabeth Dierks, Shu Chang, Kimberly Foster, Atsu Apedo, David Harden, Marta Dabros, Qi Gao, Mary Ann Pelleymounter, Jean M. Whaley, Jeffrey A. Robl, Dong Cheng, R. Michael Lawrence, Pratik Devasthale
Summary: Inhibition of MGAT2 is a potential therapeutic approach for metabolic disorders. A high-throughput screening identified the aryl dihydropyridinone compound 1 as a hit, leading to the development of stable and selective MGAT2 inhibitors. Among them, compound 21s was selected as a clinical candidate based on its efficacy in inducing weight loss and acceptable safety profile.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Andrew J. Brown, Laura J. Sharpe, Michael J. Rogers
Summary: Oxysterols are oxygenated forms of cholesterol generated via autooxidation by free radicals and enzymes, playing key roles in health and disease through binding to effector proteins and regulating transcriptional programmes affecting cell metabolism and function at low concentrations in vivo.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ji-Hyun Kim, Arukumar Nagappan, Dae Young Jung, Nanjoo Suh, Myeong Ho Jung
Summary: The study shows that histone demethylase KDM7A promotes hepatic steatosis by upregulating DGAT2 expression, leading to nonalcoholic fatty liver disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Food Science & Technology
Longxiang Li, Liping Ding, Yuting Shao, Shengwei Sun, Mengxi Wang, Jiahui Xiang, Jingjie Zhou, Guojun Wu, Zhe Song, Zhihong Xin
Summary: In this study, a feruloyl esterase DLFae4 was modified through error-prone PCR and site-directed saturation mutation to enhance its catalytic efficiency and acyltransferase activity. Five mutants with enhanced catalytic activity towards methyl ferulate were characterized. Among them, the double variant DLFae4-m5 exhibited the highest hydrolytic activity, with a decrease in Km value and an increase in Kcat/Km value. Molecular docking revealed that DLFae4-m5 formed a complex hydrogen bond network, resulting in increased catalytic activity. Furthermore, the mutation of residue Ala-341 to glycine (A341G) in DLFae4 enhanced its acyl transfer activity and efficiency, representing the highest acyltransferase activity reported so far for family VIII carboxylesterases. These findings demonstrate the effectiveness of error-prone PCR and site-directed saturation mutation in improving enzyme activity and highlight the practical application of this feruloyl esterase.
Article
Hematology
Masato Sasaki, Mina Delawary, Hidetaka Sakurai, Hideki Kobayashi, Naoki Nakao, Hiromi Tsuru, Yumiko Fukushima, Shoko Honzumi, Sachiko Moriyama, Naoya Wada, Toshio Kaneko, Keisuke Yamada, Naoki Terasaka, Kazuishi Kubota
Summary: The study explores the potential of DS-8190a as a novel therapeutic for atherosclerosis, showing its ability to increase HDL cholesterol levels and reduce atherosclerotic lesion area in monkeys and rodent models.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Plant Sciences
Yufang Pan, Wanting Zhang, Xiaofei Wang, Juliette Jouhet, Eric Marechal, Jin Liu, Xiao-Qin Xia, Hanhua Hu
Summary: This study explores the allele-specific expression of PDAT gene in the model diatom Phaeodactylum tricornutum. The results show that one of the alleles, Allele 2, can be specifically induced by decreasing nitrogen concentrations and overexpression of Allele 2 substantially enhances the accumulation of TAG. On the other hand, overexpression of Allele 1 only slightly increases TAG accumulation but leads to more serious growth inhibition. It is also found that the enzymes encoded by the two alleles have different TAG biosynthetic activity, which is mainly affected by amino acid variants in their protein sequences.
Article
Nutrition & Dietetics
Claudia Tonini, Marco Segatto, Simona Bertoli, Alessandro Leone, Arianna Mazzoli, Luisa Cigliano, Laura Barberio, Maurizio Mandala, Valentina Pallottini
Summary: This study found that maternal exposure to BPA affects hepatic lipid metabolism in female offspring, and it also reveals the potential impact of BPA on human health at doses currently considered safe.
Article
Multidisciplinary Sciences
Qiang Chen, Jianlong Du, Kun Cui, Wei Fang, Zengqi Zhao, Qiuchi Chen, Kangsen Mai, Qinghui Ai
Summary: Acetylation plays a key role in regulating inflammation induced by lipid surplus, with studies showing that high-fat diet can enhance mitochondrial fatty acid beta-oxidation and increase acetyl-CoA levels in the liver. Activation of ACLY and CEP leads to heightened p65 acetylation, exacerbating inflammation, while inactivation of SIRT1 further intensifies the inflammatory response.
Article
Cardiac & Cardiovascular Systems
Emelia J. Benjamin, Salim S. Virani, Clifton W. Callaway, Alanna M. Chamberlain, Alexander R. Chang, Susan Cheng, Stephanie E. Chiuve, Mary Cushman, Francesca N. Delling, Rajat Deo, Sarah D. de Ferranti, Jane F. Ferguson, Myriam Fornage, Cathleen Gillespie, Carmen R. Isasi, Monik C. Jimenez, Lori Chaffin Jordan, Suzanne E. Judd, Daniel Lackland, Judith H. Lichtman, Lynda Lisabeth, Simin Liu, Chris T. Longenecker, Pamela L. Lutsey, Jason S. Mackey, David B. Matchar, Kunihiro Matsushita, Michael E. Mussolino, Khurram Nasir, Martin O'Flaherty, Latha P. Palaniappan, Ambarish Pandey, Dilip K. Pandey, Mathew J. Reeves, Matthew D. Ritchey, Carlos J. Rodriguez, Gregory A. Roth, Wayne D. Rosamond, Uchechukwu K. A. Sampson, Gary M. Satou, Svati H. Shah, Nicole L. Spartano, David L. Tirschwell, Connie W. Tsao, Jenifer H. Voeks, Joshua Z. Willey, John T. Wilkins, Jason H. Y. Wu, Heather M. Alger, Sally S. Wong, Paul Muntner
Article
Pathology
Allison L. McDaniel, Heather M. Alger, Janet K. Sawyer, Kathryn L. Kelley, Nancy D. Kock, J. Mark Brown, Ryan E. Temel, Lawrence L. Rudel
AMERICAN JOURNAL OF PATHOLOGY
(2013)
Review
Food Science & Technology
Heather M. Alger, Maricel V. Maffini, Neesha R. Kulkarni, Erin D. Bongard, Thomas Neltner
COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY
(2013)
Review
Food Science & Technology
Maricel V. Maffini, Heather M. Alger, Erik D. Olson, Thomas G. Neltner
COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY
(2013)
Article
Neurosciences
Giuseppina Somma, Heather M. Alger, Ryan M. McGuire, Jim D. Kretlow, Fernanda R. Ruiz, Svetlana A. Yatsenko, Pawel Stankiewicz, Wilbur Harrison, Etai Funk, Antonio Bergamaschi, John S. Oghalai, Antonios G. Mikos, Paul A. Overbeek, Fred A. Pereira
JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
(2012)
Article
Reproductive Biology
Thomas G. Neltner, Heather M. Alger, Jack E. Leonard, Maricel V. Maffini
REPRODUCTIVE TOXICOLOGY
(2013)
Article
Medicine, General & Internal
Thomas G. Neltner, Heather M. Alger, James T. O'Reilly, Sheldon Krimsky, Lisa A. Bero, Maricel V. Maffini
JAMA INTERNAL MEDICINE
(2013)
Letter
Cardiac & Cardiovascular Systems
Heather M. Alger, Joseph H. Williams, Jason G. Walchok, Michele Bolles, Gregg C. Fonarow, Christine Rutan
CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
(2020)
Article
Cardiac & Cardiovascular Systems
Heather M. Alger, Christine Rutan, Joseph H. Williams, Jason G. Walchok, Michele Bolles, Jennifer L. Hall, Steven M. Bradley, Mitchell S. V. Elkind, Fatima Rodriguez, Tracy Y. Wang, David A. Morrow, Sandeep R. Das, James A. de Lemos
CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
(2020)
Article
Clinical Neurology
Jose G. Romano, Hannah Gardener, Iszet Campo-Bustillo, Yosef Khan, Sofie Tai, Nikesha Riley, Eric E. Smith, Ralph L. Sacco, Pooja Khatri, Heather M. Alger, Brian Mac Grory, Deepak Gulati, Navdeep S. Sangha, Jeffrey M. Craig, Karin E. Olds, Curtis G. Benesch, Adam G. Kelly, Scott S. Brehaut, Amit C. Kansara, Lee H. Schwamm
Summary: The study found that most patients with mild strokes had poor outcomes in the study. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1, with secondary outcomes including good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Factors such as age, gender, race, and baseline NIHSS score were identified as predictors of worse outcomes.
Article
Clinical Neurology
Pratyaksh K. Srivastava, Shuaiqi Zhang, Ying Xian, Hanzhang Xu, Christine Rutan, Heather M. Alger, Jason Walchok, Joseph Williams, James A. de Lemos, Marquita R. Decker-Palmer, Brooke Alhanti, Mitchell S. Elkind, Steve R. Messe, Eric E. Smith, Lee H. Schwamm, Gregg C. Fonarow
Summary: Patients with AIS and COVID-19 had younger age, greater stroke severity, longer evaluation and treatment times, decreased odds of discharge with modified Rankin Scale score of <= 2, and increased odds of in-hospital mortality compared with those with AIS and no COVID-19.
Article
Medicine, General & Internal
Gregory A. Roth, Sophia Emmons-Bell, Heather M. Alger, Steven M. Bradley, Sandeep R. Das, James A. de Lemos, Emmanuela Gakidou, Mitchell S. V. Elkind, Simon Hay, Jennifer L. Hall, Catherine O. Johnson, David A. Morrow, Fatima Rodriguez, Christine Rutan, Saate Shakil, Reed Sorensen, Laura Stevens, Tracy Y. Wang, Jason Walchok, Joseph Williams, Christopher Murray
Summary: In this retrospective cohort study involving 20,736 adults with COVID-19 in the United States, in-hospital mortality rates decreased after March and April and remained at a lower level from May through November, regardless of changes in patient characteristics.
Article
Cardiac & Cardiovascular Systems
Anjali Rao, Sagar Ranka, Colby Ayers, Nicholas Hendren, Anna Rosenblatt, Heather M. Alger, Christine Rutan, Wally Omar, Rohan Khera, Kamal Gupta, Purav Mody, Christopher DeFilippi, Sandeep R. Das, S. Susan Hedayati, James A. de Lemos
Summary: In patients hospitalized with COVID-19, acute kidney injury (AKI) is significantly associated with all-cause mortality and major adverse cardiac events, while chronic kidney disease (CKD) and end-stage kidney disease are not linked to these outcomes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Review
Cardiac & Cardiovascular Systems
David S. Siscovick, Thomas A. Barringer, Amanda M. Fretts, Jason H. Y. Wu, Alice H. Lichtenstein, Rebecca B. Costello, Penny M. Kris-Etherton, Terry A. Jacobson, Mary B. Engler, Heather M. Alger, Lawrence J. Appel, Dariush Mozaffarian
Article
Cardiac & Cardiovascular Systems
Emelia J. Benjamin, Michael J. Blaha, Stephanie E. Chiuve, Mary Cushman, Sandeep R. Das, Rajat Deo, Sarah D. de Ferranti, James Floyd, Myriam Fornage, Cathleen Gillespie, Carmen R. Isasi, Monik C. Jimenez, Lori Chaffin Jordan, Suzanne E. Judd, Daniel Lackland, Judith H. Lichtman, Lynda Lisabeth, Simin Liu, Chris T. Longenecker, Rachel H. Mackey, Kunihiro Matsushita, Dariush Mozaffarian, Michael E. Mussolino, Khurram Nasir, Robert W. Neumar, Latha Palaniappan, Dilip K. Pandey, Ravi R. Thiagarajan, Mathew J. Reeves, Matthew Ritchey, Carlos J. Rodriguez, Gregory A. Roth, Wayne D. Rosamond, Comilla Sasson, Amytis Towfighi, Connie W. Tsao, Melanie B. Turner, Salim S. Virani, Jenifer H. Voeks, Joshua Z. Willey, John T. Wilkins, Jason H. Y. Wu, Heather M. Alger, Sally S. Wong, Paul Muntner