Article
Biochemistry & Molecular Biology
Kelly L. Irving, Jessica J. King, Zoe A. E. Waller, Cameron W. Evans, Nicole M. Smith
Summary: DNA is capable of forming alternative secondary structures, including the i-motif, which was previously believed to be unstable in cellular environments. Recent studies have shown the existence of i-motifs in the human genome and their role in gene regulation. This review discusses the effects of epigenetic modifications on i-motif structure, factors influencing i-motif formation in cells, and highlights the recent progress in targeting i-motifs for biotechnology and therapeutic purposes.
Article
Oncology
Jialin Zhou, Han Xie, Jun Liu, Ruixiang Huang, Yufei Xiang, Dasheng Tian, Erbao Bian
Summary: P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a class of small regulatory RNAs that regulate transposons in germ cells and are associated with various malignant tumors. The functions and mechanisms of piRNAs in cancer are still unclear. This review summarizes the current findings on the biogenesis, function, and mechanisms of piRNAs and PIWI proteins in cancer, discusses their clinical significance as biomarkers and therapeutic tools, and presents critical questions for future research.
Review
Genetics & Heredity
Nisha Nair, Anne Barton, Anthony G. Wilson
Summary: The review highlights the key epigenetic modifications in different cell types associated with rheumatoid arthritis and discusses potential therapeutic targets focusing on epigenetic markers. It emphasizes the importance of altered epigenetic regulation in promoting the destructive behavior underlying disease pathogenesis.
Article
Multidisciplinary Sciences
Ellen L. Shrock, Richard T. Timms, Tomasz Kula, Elijah L. Mena, Anthony P. West Jr, Rui Guo, I-Hsiu Lee, Alexander A. Cohen, Lindsay G. A. McKay, Caihong Bi, Keerti, Yumei Leng, Eric Fujimura, Felix Horns, Mamie Li, Duane R. Wesemann, Anthony Griffiths, Benjamin E. Gewurz, Pamela J. Bjorkman, Stephen J. Elledge
Summary: Despite a diverse antibody repertoire, infected individuals often produce antibodies against the same epitopes within antigens. The underlying immunological mechanisms are still unknown. Mapping 376 immunodominant public epitopes and studying the corresponding antibodies, researchers found that germline-encoded sequences in antibodies play a role in recurrent recognition. They also identified human and mouse germline-encoded amino acid-binding (GRAB) motifs critical for public epitope recognition. Overall, GRAB motifs contribute to the immune system's architecture, promoting pathogen recognition and species-specific public antibody responses that can influence pathogens.
Article
Biochemistry & Molecular Biology
Yi-Hsun Ho, Rong Huang
Summary: This study determines the impact of the local chemical environment on the N-terminal SGRGK sequence on NatD-mediated Nα-acetylation of histone H4/H2A and reveals the effects of oncohistone mutations and other PTMs on NatD activity, highlighting the crosstalk between NatD and PTMs.
ACS CHEMICAL BIOLOGY
(2022)
Review
Genetics & Heredity
Hanshen Luo, Xingliang Wu, Xue-Hai Zhu, Xin Yi, Dunfeng Du, Ding-Sheng Jiang
Summary: This article provides an overview of the complex biology of histone methyltransferase SETDB1, including its role in silencing endogenous retroviruses in embryonic stem cells and its involvement in aging, tumors, and inflammatory bowel disease. The article also discusses the challenges and prospects of targeting SETDB1 for the treatment of different diseases, and suggests future research directions in the field of SETDB1 research.
EPIGENETICS & CHROMATIN
(2023)
Article
Multidisciplinary Sciences
Nazar Mashtalir, Hai T. Dao, Akshay Sankar, Hengyuan Liu, Aaron J. Corin, John D. Bagert, Eva J. Ge, Andrew R. D'Avino, Martin Filipovski, Brittany C. Michel, Geoffrey P. Dann, Tom W. Muir, Cigall Kadoch
Summary: This study identified the effects of chromatin features on mSWI/SNF activities and interactions, as well as the combinatorial contributions of complex module components, reader domains, and nucleosome engagement properties to the localization of complexes.
Review
Biochemistry & Molecular Biology
Pin Zhao, Samiullah Malik
Summary: This review describes how phosphorylation affects the transcription activity and other functions of DNA/histone modifying enzymes. Although the phosphorylated sites of these enzymes have been classified and partially explained, further research is still needed to determine their relationship with disease-associated transcriptional regulation.
CELL AND BIOSCIENCE
(2022)
Article
Medicine, Research & Experimental
Dongmei Gou, Rui Liu, Xiaoqun Shan, Haijun Deng, Chang Chen, Jin Xiang, Yi Liu, Qingzhu Gao, Zhi Li, Ailong Huang, Kai Wang, Ni Tang
Summary: The study found that the gluconeogenic enzyme PCK1 promoted the generation of S-adenosylmethionine (SAM) through the serine synthesis pathway. SAM served as a methyl donor to support H3K9me3 modification, inhibiting the oncogene S100A11. This study reveals the potential therapeutic strategy of targeting the metabolic enzyme PCK1 and H3K9 trimethylation for hepatocellular carcinoma (HCC) treatment.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
Daniel Marri, David Filipovic, Omar Kana, Shelley Tischkau, Sudin Bhattacharya
Summary: The Brain and Muscle ARNTL-Like 1 protein (BMAL1) forms heterodimers with CLOCK or NPAS2 to regulate circadian clock genes. Using machine learning models, we identified features that predict BMAL1-DNA binding and provided insights into tissue specificity. We found that histone modifications, DNA shape, and the flanking sequence of E-box motifs are sufficient predictive features for BMAL1-DNA binding.
SCIENTIFIC REPORTS
(2023)
Article
Biology
Yitong Li, Vijaya Kumar Balakrishnan, Michael Rowse, Cheng-Guo Wu, Anastasia Phoebe Bravos, Vikash K. Yadav, Ylva Ivarsson, Stefan Strack, Irina Novikova, Yongna Xing
Summary: This study demonstrates that PME-1 can regulate different families of PP2A holoenzymes and block substrate recognition. The high-resolution cryoelectron microscopy structure reveals the binding mode of PME-1 with the B56 regulatory subunit and the selective impact on PP2A-B56 holoenzymes. The findings uncover multiple mechanisms of PME-1 in suppressing holoenzyme functions and versatile activities.
Article
Cell Biology
Vanesa Alvarez, Susanne Bandau, Hao Jiang, Diana Rios-Szwed, Jens Hukelmann, Elisa Garcia-Wilson, Nicola Wiechens, Eva Griesser, Sara Ten Have, Tom Owen-Hughes, Angus Lamond, Constance Alabert
Summary: During cell proliferation, chromatin organization needs to be maintained to preserve cellular identity and genome integrity. However, DNA replication displaces DNA-bound proteins temporarily, and it is unclear how they regain access to newly replicated DNA. Through quantitative proteomics, researchers provide time-resolved binding kinetics for thousands of proteins behind replisomes in different chromatin regions, revealing that most proteins regain access within minutes. However, 25% of the identified proteins show a delay in reassociation, influenced by chromatin organization and G1 phase entry, rather than their known function or abundance in the nucleus. Additionally, DNA replication not only disrupts but also promotes the recruitment of transcription factors and chromatin remodelers, leading to a better understanding of how DNA replication contributes to programmed changes in cell memory.
Article
Biochemistry & Molecular Biology
Bingzhuang An, Haiya Cai, Bo Li, Shuo Zhang, Yonggang He, Rong Wang, Chunhai Jiao, Ying Guo, Le Xu, Yanhao Xu
Summary: Based on comparative genetic analysis, this study found that HMT and HDM may originate from Chromista and are highly conserved in green plants. Histone methylation modifications have gradually become complex and diverse during the evolution from algae to land plants, which promotes the adaptation of plants to complex and variable environments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Hyeonheui Ham, Dong Suk Park
Summary: Two strain-typing protein-encoding genes were discovered in E. amylovora strains, and these findings and approaches may enable the exploration of the genetic diversity of E. amylovora from a global perspective.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Yanjing Li, Lijie Zhao, Yuebin Zhang, Ping Wu, Ying Xu, Jun Mencius, Yongxin Zheng, Xiaoman Wang, Wancheng Xu, Naizhe Huang, Xianwen Ye, Ming Lei, Pan Shi, Changlin Tian, Chao Peng, Guohui Li, Zhijun Liu, Shu Quan, Yong Chen
Summary: This study develops methodologies to measure the methylation rate difference between different states of methylation and demonstrates that MLL proteins possess distinct product specificities. Structural analyses reveal that the dynamics of conserved tyrosine residues fine-tune the product specificity, and the variation in intramolecular interaction affects the dynamics, determining the product specificities of MLL proteins.
Article
Chemistry, Applied
Xinyi Wu, Mei Tan, Yinfei Zhu, Hanying Duan, Hosahalli S. Ramaswamy, Weibin Bai, Chao Wang
Summary: The study found that high-pressure processing and germination can improve the protein digestibility and mineral bioavailability of soybeans, reduce the content of anti-nutrients, and contribute to the utilization of soybeans in the food industry.
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
(2023)
Article
Pharmacology & Pharmacy
Xiaoqing Fan, Wojciech Krzyzanski, Dongyang Liu, Raymond S. M. Wong, Xiaoyu Yan
Summary: Recombinant human erythropoietin (rHuEPO) is an effective drug for anemia treatment in patients with chronic kidney disease. However, EPO-resistance is a significant issue. Combining rHuEPO with romiplostim, a thrombopoietin receptor agonist, can overcome EPO-resistance.
Article
Biochemical Research Methods
Yang Liu, Shuai Yan, Jie Liu, Hongzhong Liu, Ling Song, Xueting Yao, Ji Jiang, Fangqiong Li, Ke Du, Dongyang Liu, Pei Hu
Summary: In this article, a robust and sensitive HPLC coupled with tandem mass spectrometry method for determining the concentration of HSK7653 in human plasma and urine was developed and validated for the first time. The bioanalysis method has been fully validated and the results showed good sensitivity and specificity. Finally, this method was successfully applied to explore the pharmacokinetic characteristics of HSK7653 in Chinese healthy volunteers in a first-in-human study.
BIOMEDICAL CHROMATOGRAPHY
(2023)
Article
Pharmacology & Pharmacy
Miao Zhang, Zhiheng Yu, Huan Liu, Xu Wang, Haiyan Li, Xueting Yao, Dongyang Liu
Summary: HSK3486 is a central nervous system inhibitor that has demonstrated superior anesthetic properties compared to propofol. The high liver extraction ratio and limited susceptibility to rifampicin make HSK3486 suitable for a wide range of patients. However, in order to expand its indications, it is crucial to assess the systemic exposure of HSK3486 in specific populations and consider the gene polymorphism of UGT1A9, its main metabolic enzyme. A physiologically based pharmacokinetic model of HSK3486 was developed in 2019 to support model-informed drug development (MIDD) and predict the exposure in different populations. The predicted results showed slight increase in hepatic impairment and elderly patients, no change in severe renal impairment and neonates, and significant decrease in pediatric patients. The model also estimated increased exposure in the obese population and poor metabolizers of UGT1A9. Obesity and genetic polymorphisms are unlikely to result in clinically significant changes in anesthesia at the standard dose in adults.
BIOPHARMACEUTICS & DRUG DISPOSITION
(2023)
Article
Biochemistry & Molecular Biology
Hao Wang, Zhaoyue Zhang, Haicheng Li, Jinzhao Li, Hanshuang Li, Mingzhu Liu, Pengfei Liang, Qilemuge Xi, Yongqiang Xing, Lei Yang, Yongchun Zuo
Summary: This study developed a computational biology method using single-cell transcriptome to identify and predict pathological cell subpopulations of early-onset preeclampsia (PE). The TURF_XGB method achieved high accuracy and recall rates in classifying healthy placenta subpopulations, revealing the heterogeneity of placental biology. Additionally, the analysis revealed the involvement of dendritic cells and the role of C1QB and C1QC in mediating inflammation and driving the development of PE. The study also developed a risk stratification card for preeclampsia classification.
CELL AND BIOSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Miao Zhang, Zihan Lei, Ziheng Yu, Xueting Yao, Haiyan Li, Min Xu, Dongyang Liu
Summary: PB-201 is the second glucokinase activator in the world to enter phase III clinical trials for the treatment of type 2 diabetes mellitus. With its efficacy advantages and favorable characteristics in absorption, distribution, metabolism, and excretion, PB-201 has a broad indication population. Estimating PB-201 exposure in specific populations is crucial to understand its pharmacokinetic characteristics and avoid hypoglycemia. The influence of internal and external factors on PB-201 exposure deserves attention for precision dosing and future clinical studies.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Xueting Yao, Jiawei Zhou, Ling Song, Yupeng Ren, Pei Hu, Dongyang Liu
Summary: Sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as dapagliflozin, canagliflozin, and empagliflozin, show special benefits in reducing weight and heart failure risks for patients with type 2 diabetes mellitus (T2DM). A quantitative relationship between pharmacokinetics, pharmacodynamics, and disease end points (PK/PD/end points) was developed using data from clinical studies. A novel biomarker, the change of urine glucose excretion (UGE) from baseline normalized by fasting plasma glucose (delta UGE(c)), was identified to bridge healthy subjects and T2DM patients. This relationship offers insight into long-term efficacy prediction for SGLT2 inhibitors.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Chemistry, Analytical
Zhe Hou, Lei Zhang, Xuan Guo, Hui Li, Xiaodong Li, Jing Dong, Guangqin Zhang, Dongyang Liu
Summary: The study developed a validated method using liquid chromatography-tandem mass spectrometry to quantify nine important transporter proteins in human tissues and organs. The method was validated for specificity, linearity, accuracy, precision, and stability. The results showed that the method is sensitive and efficient for quantification of the transporters.
SEPARATION SCIENCE PLUS
(2023)
Article
Pharmacology & Pharmacy
Yaxin Liu, Yun Kuang, Min Hai, Cheng Cui, Dongyang Liu, Guoping Yang
Summary: The exposure to ticagrelor is higher in East Asians, resulting in an increased risk of bleeding. A population pharmacokinetic model was developed and machine learning methods were used to construct bleeding risk models. The Random Forest model performed the best and a lower bleeding risk ticagrelor regimen can be obtained using this model.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Miao Zhang, Shudong Zhang, Zhiheng Yu, Xueting Yao, Zihan Lei, Pangke Yan, Nan Wu, Xu Wang, Qin Hu, Dongyang Liu
Summary: HSK7653 is a candidate drug for the treatment of type 2 diabetes mellitus and its major elimination pathway is renal excretion. Evaluating the exposure of HSK7653 in patients with renal impairment and geriatric populations is important to bring more benefits to the patients. A PBPK model based on in vitro experimental results and in vivo renal clearance was developed to evaluate the effects of physiological factors and food on HSK7653 exposure.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Hanshuang Li, Chunshen Long, Yan Hong, Liaofu Luo, Yongchun Zuo
Summary: This study quantitatively evaluated the differentiation potency of stem cells using the Hopfield neural network and found that it can be approximated by Hopfield energy values. The analysis of the energy landscape in embryogenesis and cell reprogramming processes revealed that cell fate decision is a continuous process. The study also deciphered the dynamics of the gene regulatory network involved in driving cell fate transition. These findings propose a new energy indicator for characterizing cellular differentiation potency and provide insights into the potential mechanism of cellular plasticity.
Article
Pharmacology & Pharmacy
Ling Song, Fangrui Cao, Shu Niu, Michael Xu, Ruifang Liang, Ke Ding, Zhigang Lin, Xueting Yao, Dongyang Liu
Summary: This study developed a population PK/PD model for PB201 and predicted its effects in a Chinese population with type 2 diabetes. The results showed that PB201 had persistent and dose-dependent glycemic effects and low risk of side effects.
CLINICAL PHARMACOKINETICS
(2023)
Article
Endocrinology & Metabolism
Cheng Cui, Fangrui Cao, Iok Ian Kong, Qinghe Wu, Fangqiong Li, Haiyan Li, Dongyang Liu
Summary: This study aims to use a model-informed drug development approach to facilitate decision making and expedite the clinical progress of cofrogliptin for the treatment of type 2 diabetes. The study successfully achieved waiver approval for the phase 2b dose-finding study, paving the way for the clinical development of cofrogliptin and other DPP-4 inhibitors.
DIABETES OBESITY & METABOLISM
(2023)
Article
Infectious Diseases
Lin Gan, Xiaoxin Xie, Yanhua Fu, Xiaoyan Yang, Shujing Ma, Linghong Kong, Chunli Song, Yebing Song, Tingting Ren, Hai Long
Summary: This study evaluated the safety and efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) and Dolutegravir plus Lamivudine (DTG + 3TC) in a real-world setting and obtained the first dataset for switching to these regimens in a Chinese population. The results showed that both regimens were well tolerated and effective for switching HIV-1 infection therapy.
INFECTIOUS DISEASES AND THERAPY
(2023)
Article
Pharmacology & Pharmacy
Huan Wang, Qi Liu, Muhan Jiang, Chunli Song, Dongyang Liu
Summary: This study used a kinetic-pharmacodynamic model and exposure-response analysis to describe the changes in bone mineral density in different doses of zoledronic acid and established the relationship between dose and acute phase reaction.
FRONTIERS IN PHARMACOLOGY
(2023)