Article
Food Science & Technology
Alexandre Ferro Aissa, Volodymyr P. Tryndyak, Aline de Conti, Ana Rita Thomazela Machado, Katiuska Tuttis, Carla da Silva Machado, Livia Cristina Hernandes, Patrick Wellington da Silva Santos, Juliana Mara Serpeloni, Igor P. Pogribny, Lusania Maria Greggi Antunes
Summary: A diet deficient in donors of methyl group, such as methionine, affects DNA methylation, hepatic lipid metabolism, and other epigenetic mechanisms. This study investigated the effects of methionine-supplemented or methionine-deficient diets on chromatin-modifying genes, global DNA methylation, genes related to lipid metabolism, and microRNAs in mouse liver. Both diets altered gene expression, global DNA methylation, and microRNA expression, with the methionine-deficient diet having a more substantial effect.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Cell Biology
Zhenghui Jing, Haifeng Zhang, Yunjie Wen, Shiyu Cui, Yuhua Ren, Rong Liu, Sirui Duan, Wenbao Zhao, Lihong Fan
Summary: This study investigated the transcriptomic and epigenetic alterations in ClC-3 deficient mice consuming a normal diet. It was found that ClC-3 deletion affected body size, glucose and lipid metabolism, as well as the weight of important organs. ClC-3 influenced the transcriptional expression and DNA methylation levels of glucose metabolism-related genes. Personalized diet interventions may have the potential to reverse these changes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Md. Shahid Sarwar, David Cheng, Rebecca Mary Peter, Ahmad Shannar, Pochung Chou, Lujing Wang, Renyi Wu, Davit Sargsyan, Michael Goedken, Yujue Wang, Xiaoyang Su, Ronald P. Hart, Ah-Ng Kong
Summary: This study investigated the regulation of cellular metabolism, DNA methylation, and transcriptome status in the kidney of diabetic nephropathy mice under high glucose conditions. The results showed that high glucose regulated cellular metabolites, metabolic signaling pathways, gene expression, and DNA methylation, which may be involved in the progression of diabetic nephropathy.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Nutrition & Dietetics
Rita Castro, Courtney A. Whalen, Sean Gullette, Floyd J. Mattie, Cristina Florindo, Sandra G. Heil, Neil K. Huang, Thomas Neuberger, A. Catharine Ross
Summary: This pilot study investigated the effects of mild HHcy induced by nutritional manipulation of the methionine metabolism on disease progression and specific epigenetic changes in mice. Results showed the presence of nutritional ketosis in KD and LMKD mice, with mild HHcy only detected in LMKD-fed mice. Significantly different levels of some markers were observed between control mice and the other two groups, suggesting potential factors influencing the progression of HHcy. Further studies with a larger sample size are needed to confirm these preliminary observations.
Article
Biochemistry & Molecular Biology
Yuta Takahashi, Mariana Morales Valencia, Yang Yu, Yasuo Ouchi, Kazuki Takahashi, Maxim Nikolaievich Shokhirev, Kathryn Lande, April E. Williams, Chiara Fresia, Masakazu Kurita, Tomoaki Hishida, Kensaku Shojima, Fumiyuki Hatanaka, Estrella Nunez-Delicado, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte
Summary: Research demonstrates that DNA methylation can be transmitted from parents to offspring in mice, and this trans-generational inheritance can persist across multiple generations. This finding is significant in understanding trans-generational epigenetic inheritance in mammals and may have implications in evolutionary biology as well as the etiology, diagnosis, and prevention of non-genetically inherited human diseases.
Editorial Material
Multidisciplinary Sciences
Martyna W. Sroka, Christopher R. Vakoc
Summary: Two studies have shown that certain cancers are driven by genetic changes in the NSD3 protein, which alter its enzymatic activity. Biochemical and structural characterization suggest a potential route for pharmacological reversal.
Article
Endocrinology & Metabolism
Lukasz Witucki, Hieronim Jakubowski
Summary: Loss of CBS or PHF8 leads to severe intellectual disability. Depletion of CBS results in reduced PHF8 expression, increased mTOR expression and phosphorylation, downregulated autophagy, and accumulation of Aβ protein.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Food Science & Technology
Iraia Munoa-Hoyos, Manu Araolaza, Itziar Urizar-Arenaza, Marta Gianzo, Jon Irazusta, Nerea Subiran
Summary: The study found that chronic morphine treatment induces changes in DNA methylation and histone modification in vivo, potentially affecting gene expression regulation at a physiological level. Morphine-induced epigenetic modification occurs in a sex-dependent manner, revealing different underlying mechanisms in male and female mice.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Physiology
Daoyu Zhang, Yongfeng Zhou, Rong Huang, Yanhui Zhai, Di Wu, Xinglan An, Sheng Zhang, Lijing Shi, Qi Li, Xiangjie Kong, Hao Yu, Ziyi Li
Summary: The study investigated the role of lncRNAs in the regulation of embryonic development by analyzing their expression patterns in porcine embryos. Knocking down the expression of a specific lncRNA (lncT) was found to inhibit embryonic development and affect genetic markers and gene expression associated with development. SIN3A was identified as one of the downstream genes regulated by lncT in embryonic development.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Medicine, Research & Experimental
Xinjing Mao, Yunlong Hou, Chao Fang, Kun Ma, Shixiong Zhang, Zhifang Guo, Ning Kang, Kunxu Niu, Xiaogang Shen, Yawen Li, Yuning Jiang, Yahui Song, Lu Wang, Hongrong Li, Liping Chang, Cong Wei, Yiling Wu, Mengnan Li
Summary: This study explored the antiaging effects of Bazi Bushen (BZBS), a traditional Chinese medicine, in naturally aging mice. The results showed that BZBS treatment restored age-associated methylation decline and rejuvenated methylation age. In addition, BZBS improved memory and muscular endurance, reduced frailty score and liver pathological changes. Overall, this research revealed the potential of BZBS in extending healthspan and provided insights into its mechanism of action in age-related disease treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Lemeng Feng, Chao Wang, Cheng Zhang, Wulong Zhang, Weitao Song
Summary: Glaucoma is a leading cause of irreversible blindness worldwide, and lowering intraocular pressure is currently the only effective clinical treatment. However, there is a lack of long-acting drugs to lower intraocular pressure, and some patients still experience loss of retinal ganglion cells despite good control of intraocular pressure. Currently, there are no effective clinical methods for neuroprotection and regeneration in glaucoma. Recent studies have shown that epigenetics plays a crucial role in neuroprotection and regeneration in glaucoma.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Cell Biology
Hao Song, Juanli Chen, Jin Huang, Peng Sun, Yanming Liu, Li Xu, Chuanfei Wei, Xin Mu, Xianjie Lu, Wei Wang, Nan Zhang, Miwei Shang, Mei Mo, Wei Zhang, Hui Zhao, Fabin Han
Summary: Parkinson's disease (PD) is a common neurodegenerative disorder caused by genetic, epigenetic, and environmental factors. Recent advance in genomics and epigenetics have revealed epigenetic mechanisms in PD. These epigenetic modifications include DNA methylation, post-translational histone modifications, chromatin remodeling, and RNA-based mechanisms, which regulate cellular functions in almost all cells. Epigenetic alterations are involved in multiple aspects of neuronal development and neurodegeneration in PD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Oncology
Yuhao Zhao, Mao Yang, Shijia Wang, Sk Jahir Abbas, Junzhe Zhang, Yongsheng Li, Rong Shao, Yingbin Liu
Summary: This review focuses on the mechanistic insights of DNA, histone, and RNA methylation in regulating the progression of pancreatic cancer. The roles of methylation regulators in modulating gene expression associated with cell proliferation, invasion, and apoptosis are discussed. Recent clinical trials on methylation drug targeting are also explored. Understanding the novel regulatory mechanisms of methylation modification may offer alternative opportunities to improve therapeutic efficacy in combating this devastating disease.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tiziana Raia, Federica Armeli, Rosaria A. Cavallaro, Giampiero Ferraguti, Rita Businaro, Marco Lucarelli, Andrea Fuso
Summary: DNA methylation, the main epigenetic modification, influences neurodegeneration. In this study, the researchers investigated the effects of S-adenosylmethionine (SAM) supplementation during the perinatal period on the development of Alzheimer's disease (AD) symptoms in TgCRND8 mice. They found that both post-weaning and perinatal SAM supplementation effectively reduced PSEN1 expression and amyloid deposition in adult mice. These findings emphasize the role of early-life epigenetic memory and methyl donor availability in promoting healthy aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Keren Xu, Shaobo Li, Ivo S. Muskens, Natalina Elliott, Swe Swe Myint, Priyatama Pandey, Helen M. Hansen, Libby M. Morimoto, Alice Y. Kang, Xiaomei Ma, Catherine Metayer, Beth A. Mueller, Irene Roberts, Kyle M. Walsh, Steve Horvath, Joseph L. Wiemels, Adam J. Smith
Summary: The study revealed that accelerated epigenetic aging in the blood of Down syndrome (DS) patients begins prenatally and is associated with somatic GATA1 mutations. DS newborns showed a significant increase in DNAmSkinBloodClock, but were not associated with epigenetic gestational age acceleration.
Article
Genetics & Heredity
Hesham M. Ismail, Navaneethakrishnan Krishnamoorthy, Nader Al-Dewik, Hatem Zayed, Nura A. Mohamed, Valeria Di Giacomo, Sapna Gupta, Johannes Haberle, Beat Thony, Henk J. Blom, Waren D. Kruger, Tawfeg Ben-Omran, Gheyath K. Nasrallah
Article
Biotechnology & Applied Microbiology
Hyung-Ok Lee, Lorena Gallego-Villar, Hiu Man Grisch-Chan, Johannes Haberle, Beat Thony, Warren D. Kruger
HUMAN GENE THERAPY
(2019)
Article
Endocrinology & Metabolism
Nader Al-Dewik, Alaa Ali, Yassmin Mahmoud, Noora Shahbeck, Rehab Ali, Laila Mahmoud, Mariam Al-Mureikhi, Fatma Al-Mesaifri, Sara Musa, Karen El-Akouri, Mariam Almulla, Reem Al Saadi, Gheyath K. Nasrallah, Muthanna Samara, Ghassan Abdoh, Hilal Al Rifai, Johannes Haberle, Beat Thony, Warren Kruger, Henk J. Blom, Tawfeg Ben-Omran
JOURNAL OF INHERITED METABOLIC DISEASE
(2019)
Article
Cardiac & Cardiovascular Systems
Sean X. Gu, Vijay K. Sonkar, Parmeshwar B. Katare, Rahul Kumar, Warren D. Kruger, Erland Arning, Teodoro Bottiglieri, Steven R. Lentz, Sanjana Dayal
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2020)
Article
Biochemistry & Molecular Biology
Sibel Cal-Kayitmazbatir, Eylem Kulkoyluoglu-Cotul, Jacqueline Growe, Christopher P. Selby, Seth D. Rhoades, Dania Malik, Hasimcan Oner, Hande Asimgil, Lauren J. Francey, Aziz Sancar, Warren D. Kruger, John B. Hogenesch, Aalim Weljie, Ron C. Anafi, Ibrahim Halil Kavakli
Summary: The study reveals a functional interaction between cystathionine beta-synthase (CBS) and the core circadian protein cryptochrome 1 (CRY1), impacting circadian rhythms and metabolic health. CRY1 modulates CBS activity, influencing both circadian physiology and metabolic pathways. The CBS-CRY1 binding serves as a post-translational switch to regulate cellular circadian physiology and metabolic control.
Article
Biochemistry & Molecular Biology
Sapna Gupta, Liqun Wang, Michael J. Slifker, Kathy Q. Cai, Kenneth N. Maclean, Brandi Wasek, Teodoro Bottiglieri, Warren D. Kruger
Summary: Research indicates that neonatal lethality in CBS-null mice is mainly due to liver failure caused by elevated levels of methionine in the blood, leading to increased stress on various related pathways and cellular responses.
Article
Endocrinology & Metabolism
Hyung-Ok Lee, Christiana O. Salami, Dolan Sondhi, Stephen M. Kaminsky, Ronald G. Crystal, Warren D. Kruger
Summary: The study demonstrates that gene therapy using AAVrh.10 is highly effective in treating CBS deficiency in mice, leading to a gradual increase in liver CBS activity and a decrease in serum tHcy, as well as correction of related phenotypes. The success of this treatment approach in mice provides support for future human trials.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Review
Genetics & Heredity
Warren D. Kruger
Summary: Inherited errors of metabolism are a group of recessive genetic diseases caused by missense mutations, leading to cellular metabolic disorders. Deficiency of cystathionine beta-synthase is an example, resulting in elevated blood homocysteine levels and various symptoms. Modulation of the intracellular protein folding environment may offer a potential therapeutic strategy for treating this condition.
Article
Multidisciplinary Sciences
Kai-Ti Chang, Jan Jezek, Alicia N. Campbell, David C. Stieg, Zachary A. Kiss, Kevin Kemper, Ping Jiang, Hyung-Ok Lee, Warren D. Kruger, Peter M. van Hasselt, Randy Strich
Summary: MED13L syndrome is a developmental disorder characterized by intellectual disability, heart malformation, and hypotonia. Research has found that cells carrying the MED13L(S1497F/fs) allele have mitochondrial dysfunction, likely due to mis-localization of cyclin C.
Article
Oncology
Alexander Y. Deneka, Anna S. Nikonova, Hyung-Ok Lee, Warren D. Kruger, Erica A. Golemis
Summary: Elevated rates of glycolysis in cancer cells promote tumor growth, and the upregulation of NEDD9 protein in tumors can support tumor growth by promoting invasion and metastasis. This study reveals a new role for NEDD9 in glycolysis, as NEDD9 knockdown significantly impairs glycolysis in lung cancer cells, accompanied by downregulation of glycolytic enzymes. The study also suggests a negative feedback loop between NEDD9 and glycolytic enzymes that may contribute to the aggressive growth of advanced tumors.
Article
Biochemistry & Molecular Biology
Baiqing Tang, Hyung-Ok Lee, Sapna Gupta, Liqun Wang, Alison M. Kurimchak, James S. Duncan, Warren D. Kruger
Summary: MTAP is a key enzyme that converts MTA into methionine, and its inactivation is commonly found in various cancers. Our study confirms that MTAP-deleted cells have increased MTA accumulation and reduced protein sDMAylation. Additionally, we demonstrate that extracellular MTA can inhibit protein sDMAylation, which can affect the function of FUBP proteins.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Tomas Majtan, Viktor Kozich, Warren D. Kruger
Summary: Homocystinuria, a common metabolic disorder, is characterized by increased homocysteine levels, leading to various clinical complications. Current treatment primarily involves dietary interventions, but alternative therapies such as enzyme and gene therapies have been explored.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Correction
Biotechnology & Applied Microbiology
Nisha Padmanabhan, Huang Kie Kyon, Arnoud Boot, Kevin Lim, Supriya Srivastava, Shuwen Chen, Zhiyuan Wu, Hyung-Ok Lee, Vineeth T. Mukundan, Charlene Chan, Yarn Kit Chan, Ong Xuewen, Jason J. Pitt, Zul Fazreen Adam Isa, Manjie Xing, Ming Hui Lee, Angie Lay Keng Tan, Shamaine Ho Wei Ting, Micah A. Luftig, Dennis Kappei, Warren D. Kruger, Jinsong Bian, Ying Swan Ho, Ming Teh, Steve George Rozen, Patrick Tan
Article
Biotechnology & Applied Microbiology
Nisha Padmanabhan, Huang Kie Kyon, Arnoud Boot, Kevin Lim, Supriya Srivastava, Shuwen Chen, Zhiyuan Wu, Hyung-O K. Lee, Vineeth T. Mukundan, Charlene Chan, Yarn Kit Chan, Ong Xuewen, Jason J. Pitt, Zul Fazreen Adam Isa, Manjie Xing, Ming Hui Lee, Angie Lay Keng Tan, Shamaine Ho Wei Ting, Micah A. Luftig, Dennis Kappei, Warren D. Kruger, Jinsong Bian, Ying Swan Ho, Ming Teh, Steve George Rozen, Patrick Tan
Summary: The study identified CBS as a crucial epigenetic target in CIMP GC and demonstrated the significant association of CBS epimutations with CIMP in other cancers. Loss of CBS resulted in DNA methylation changes and increased inflammation, suggesting H2S donors as a potential new therapy for CBS-silenced lesions.
Article
Oncology
Ralph Francescone, Debora Barbosa Vendramini-Costa, Janusz Franco-Barraza, Jessica Wagner, Alexander Muir, Allison N. Lau, Linara Gabitova, Tatiana Pazina, Sapna Gupta, Tiffany Luong, Dustin Rollins, Ruchi Malik, Roshan J. Thapa, Diana Restifo, Yan Zhou, Kathy Q. Cai, Harvey H. Hensley, Yinfei Tan, Warren D. Kruger, Karthik Devarajan, Siddharth Balachandran, Andres J. Klein-Szanto, Huamin Wang, Wafik S. El-Deiry, Matthew G. Vander Heiden, Suraj Peri, Kerry S. Campbell, Igor Astsaturov, Edna Cukierman
Summary: The study identified Netrin G1 as a promoter of PDAC tumorigenesis through its effects on CAFs and metabolism. Inhibiting NetG1 showed potential in limiting tumor growth, indicating it as a possible target for PDAC treatment. The findings also highlighted the interplay between fibroblasts, metabolism, and immune response in pancreatic cancer.