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Design, molecular characterization and therapeutic investigation of a novel CCR8 peptide antagonist that attenuates acute liver injury by inhibiting infiltration and activation of macrophages

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Acta Pharmaceutica Sinica B 2025年第4期15卷 2114-2133页

作者： Geervliet, Eline Arora, Sahil Donohue, Dagmara Antonio de Albuquerque Pinheiro, Carlos Terstappen, Leon W.M.M. Schasfoort, Richard Paez, Julieta Kumar, Raj Bansal, Ruchi Personalized Diagnostics and Therapeutics Department of Bioengineering Technologies Technical Medical Centre Faculty of Science and Technology University of Twente Netherlands Institute of Molecular Pathobiochemistry Experimental Gene Therapy and Clinical Chemistry RWTH University Hospital Aachen Germany Department of Pharmaceutical Sciences and Natural Products School of Health Sciences Central University of Punjab India Developmental BioEngineering Department of Bioengineering Technologies Technical Medical Centre Faculty of Science and Technology University of Twente Netherlands

During liver injury, intrahepatic macrophage compartment is augmented by circulating monocytes that infiltrate the liver driven by C–C motif chemokine ligand/C–C motif chemokine receptor (CCL/CCR) axis including CCL1‒CCR8 axis, thereby contributing to liver inflammation. Numerous small molecular receptor antagonists, including R243, have been developed for targeting CCR8;however, these agents face challenges in clinical translation, potentially attributed to their poor pharmacokinetic profiles, lack of target specificity, and potential adverse effects. In this study, we designed four CCR8 antagonizing peptides (AP8i-AP8iv) and performed molecular characterization in-silico and therapeutic investigation in-vitro and in-vivo. Based on in-silico docking, molecular dynamic simulation using homology build model and in-vitro (competitive) binding studies, AP8ii (YEWRFYHG) evidenced highly favorable and selective interactions at the CCR8-active site. AP8ii inhibited CCL1-driven chemotaxis and LPS/IFNγ-induced pro-inflammatory activation of monocytes-macrophages in-vitro. In a CCl₄-induced acute liver injury mouse model, AP8ii treatment decreased intrahepatic infiltration of circulating monocytes. Moreover, AP8ii reduced liver inflammation, as indicated by decreased F4/80, IL6 and iNOS expression, diminished ALT levels, and attenuated fibrosis, as indicated by reduced collagen-I expression. In conclusion, we report a novel CCR8-antagonizing peptide that inhibited CCL1-driven intrahepatic monocytes infiltration and differentiation into pro-inflammatory phenotype, consequently ameliorating liver inflammation and fibrogenesis in an acute liver injury mouse model. © 2025 The Authors

关键词： CCL1‒CCR8 axis CCR8 antagonizing peptide In silico molecular docking In vitro chemotaxis In vivo acute liver injury Intrahepatic monocyte infiltration and differentiation Liver inflammation

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Plasma Advanced Glycation End-Products, Fructosamine and Glycosaminoglycans as Protein Glycation Biomarkers of Oxidative Stress During Healthy Human Aging

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Proceedings of the National Academy of Sciences India Section B - Biological Sciences 2025年 1-11页

作者： Mehdi, Mohammad Murtaza Department of Biochemistry Faculty of Sciences University of Allahabad Uttar Pradesh Allahabad 211002 India Department of Biochemistry School of Bioengineering and Biosciences Lovely Faculty of Technology and Sciences Lovely Professional University Punjab Phagwara 144411 India

The increase in oxidative stress that causes damage to various biomolecules and altering enzymatic processes is associated with aging. Advanced glycation end-products (AGE) and fructosamine are formed due to various chemical transformations as stable end-stage adducts. Glycosaminoglycans (GAGs) are the main complex macromolecules of the extracellular matrix and the major structural components of proteoglycans. Ceruloplasmin is a major copper-carrying protein, and myeloperoxidase (MPO) is released extracellularly during degranulation. The present study is focused on the assessment of AGEs, fructosamine, GAGs, ceruloplasmin and MPO, along with hydroxyl (OH), nitric oxide (NO) and salicylate probe-based radical scavenging activities, which have been evaluated to be established as biomarkers for oxidative stress during aging in humans by measuring plasma samples of 85 normal healthy subjects of both sexes (48 males and 37 females) between the ages of 20 and 81 years. The AGEs, fructosamine, ceruloplasmin, myeloperoxidase and GAGs are observed to be positively correlated, and the OH, NO and salicylate probe-based radical scavenging activities are observed to be negatively correlated with human age. This study provides an elaborate view of the status of protein glycation along with enzymatic alterations as valid biomarkers of age-dependent oxidative stress. © The Author(s), under exclusive licence to The National Academy of Sciences, India 2025.

关键词： Advanced glycation end-products Aging Ceruloplasmin Fructosamine Glycosaminoglycans Myeloperoxidase

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Deep Deashing of Bituminous Coal to Prepare Ultra-Clean Coal by Physicochemical Approach

Deep Deashing of Bituminous Coal to Prepare Ultra-Clean Coal...

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Energy Technologies and CO2 Management symposium, 2025, held as part of the TMS Annual Meeting and Exhibition, TMS 2025

作者： Xie, Chenxi Lin, Kun Su, Zijian Yang, Guang Zhang, Yuanbo School of Minerals Processing and Bioengineering Central South University Hunan Changsha410083 China Faculty of Materials Metallurgy and Chemistry Jiangxi University of Science and Technology Jiangxi Ganzhou341000 China

ISBN: (纸本)9783031806872

The high ash content of coal is the main reason limiting its high-value utilization. The ultra-clean coalUltra-clean coal can be used as precursors for hard carbon materials, activated carbon, and carbon molecular sieves. The current methods of coal deashing are mainly physical or chemical. Bituminous coal is a commonly used precursor for carbon-based materialsCarbon-based material, of which the main component of ash is silica. In this study, a physicochemical method was used for deep deashingChemical deashing of bituminous coal to prepare ultra-clean coalUltra-clean coal. Quartz and other minerals in the coal were removed by flotation pretreatment. The coal was then deeply deashed by NaOH-HCl leaching. Residual minerals reacted with NaOH to generate water-soluble sodium silicate and sodium silicoaluminates that were soluble in acid and removed. The results indicated that ultra-clean coal with a content of 0.9% can be obtained through the flotation processFlotation process and subsequent alkali-acid leaching. © The Minerals, Metals & Materials Society 2025.

关键词： Leaching

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Transcriptome profiling unravels improved ethanol production and acetic acid tolerance in yeast by preculture of wheat gluten hydrolysates

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Journal of Biotechnology 2025年 403卷 103-114页

作者： Li, Qing Jiang, Min Yang, Huirong Zong, Xuyan Coldea, Teodora Emilia Cheng, Chao Zhao, Haifeng School of Food Science and Engineering South China University of Technology Guangzhou510640 China College of Food Science and Technology Southwest Minzu University Chengdu610041 China College of Bioengineering Sichuan University of Science and Engineering Yibin644000 China Faculty of Food Science and Technology University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca Cluj-Napoca400372 Romania Research Institute for Food Nutrition and Human Health Guangzhou510640 China

The effects of wheat gluten hydrolysates (WGH) preculture on yeast acetic acid tolerance and fermentation performances were investigated. Results showed that WGH preculture significantly increased yeast growth and viability under acetic acid stress. Particularly, the WGH fraction precipitated with 90 % (v/v) gradient ethanol (WGH-C) preculture significantly improved yeast cell membrane integrity and H+-ATPase activity, thereby decreasing the intracellular accumulation of ROS and acetic acid. Meanwhile, WGH-C preculture promoted the ethanol production efficiency, shortening the fermentation lag time by 12 h and increasing the ethanol yield by 37.46 %. These improvements were attributed to that WGH-C preculture regulated intracellular amino acid composition and transport protein related gene expression of yeast. Transcriptome profiling demonstrated that the cell wall and plasma membrane structures were remodeled, reducing the oxidative stress induced by acetic acid. Furthermore, regulation of energy metabolism and transporter activity are prime mechanisms in improving acetic acid tolerance and fermentation efficiency of yeast. © 2025 Elsevier B.V.

关键词： Acetic acid tolerance Biorefinery Ethanol production Saccharomyces cerevisiae Wheat gluten hydrolysates

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Multi-hazard Risk Unveiled: Pioneering Techniques for Comprehensive Risk Analysis and Mitigation

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Operations Research Forum 2025年第1期6卷 1-26页

作者： Mahato, Payal Srivastava, Supriya Jogi, Swati Pandey, Sadanand Faculty of Management Sciences Shoolini University Himachal Pradesh Solan 173229 India School of Bioengineering and Food Technology Faculty of Applied Sciences and Biotechnology Shoolini University Himachal Pradesh Solan 173229 India Department of Chemistry College of Natural Science Yeungnam University 280 Daehak-Ro Gyeongbuk Gyeongsan 3854 South Korea

This study presents a systematic literature review of techniques and methods for assessing and reducing multi-hazards, with a focus on developing nations. The primary aim is to identify the most commonly used multi-hazard assessment approaches, evaluate their effectiveness, and highlight their significance for sustainability and disaster risk reduction. Addressing gaps in the literature, the study emphasizes underexplored dimensions of multi-hazard assessments in vulnerable regions. Using the PRISMA framework, 62 articles from the Scopus database (2013–2022) were reviewed based on predefined inclusion and exclusion criteria. Analytical methods include descriptive and citation analysis, keyword co-occurrence analysis via VOSviewer, and bibliometric tools, while SPSS 27 and ArcGIS 10.4 software were utilized for graphical and spatial analysis. The review identifies the Analytic Hierarchy Process (AHP), Multi-Criteria Decision-Making (MCDM), and weighted methods as prevalent techniques, particularly for their integration with geospatial technologies to assign variable weights in risk evaluation. Quantitative methods dominated the studies (40 articles), followed by mixed-method approaches, with only five articles applying qualitative methods exclusively. Research trends reveal a growing focus on multi-hazards from 2013 to 2022, particularly in developed countries such as the UK (20%), China (14%), Italy (12%), and the USA (10%), while developing nations like India, Colombia, Switzerland, Portugal, and Nepal contributed less (4% each). Common hazards studied include earthquakes and floods, reflecting their significant impact on global economies and societies. Key vulnerabilities analyzed were physical and socio-economic, though systemic and environmental dimensions remain underexplored. Frequent keywords such as “multi-hazard” and “risk assessment” underscore the global focus on integrated risk management. This review offers valuable insights for policymakers, stakeholde

关键词： Disaster management Multi-hazard Risk analysis Risk assessment Risk reduction

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The interplay between histone modifications and nuclear lamina in genome regulation

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Journal of Genetics and Genomics 2025年第1期52卷 24-38页

作者： Chang Sun Yanjing Zhao Liping Guo Juhui Qiu Qin Peng Institute of Systems and Physical Biology Shenzhen Bay LaboratoryShenzhen 518132China Faculty of Medicine and Health Sciences Barcelona UniversityBarcelonaSpain Division of Life Science Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina School of Biology and Biological Engineering South China University of TechnologyGuangzhouGuangdong 510006China Key Laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsCollege of BioengineeringChongqing UniversityChongqing 400030China

Gene expression is regulated by chromatin architecture and epigenetic remodeling in cell homeostasis and *** modifications act as the key factors to modulate the chromatin *** histone modifications are strongly associated with the localization of *** primarily localizes at the nuclear periphery,where it interacts with lamina proteins to suppress gene *** this review,we summarize the potential bridges that have regulatory functions of histone modifications in chromatin organization and transcriptional regulation at the nuclear *** use lamina-associated domains(LADs)as examples to elucidate the biological roles of the interactions between histone modifications and nuclear lamina in cell differentiation and *** the end,we highlight the technologies that are currently used to identify and visualize histone modifications and LADs,which could provide spatiotemporal information for understanding their regulatory functions in gene expression and discovering new targets for diseases.

关键词： Histone modifications Chromatin organization Nuclear lamina Lamina-associated domain Genome regulation Cell differentiation

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From gene editing to tumor eradication: The CRISPR revolution in cancer therapy

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Progress in Biophysics and Molecular Biology 2025年 196卷 114-131页

作者： Ali, Ashiq Azmat, Urooj Khatoon, Aisha Akbar, Kaynaat Murtaza, Bilal Ji, Ziyi Irshad, Urooj Su, Zhongjing Department of Histology and Embryology Shantou University Medical College Shantou China Department of Zoology Wildlife and Fisheries Faculty of Sciences University of Agriculture Punjab Faisalabad 38040 Pakistan Department of Pathology University of Agriculture Faisalabad Pakistan School of Bioengineering Dalian University of Science and Technology Dalian China Department of Zoology Faculty of Sciences Superior University Lahore Pakistan

Cancer continues to be a significant worldwide health concern, characterized by high rates of occurrence and death. Unfortunately, existing treatments frequently fall short of delivering satisfying therapeutic outcomes. Immunotherapy has ushered in a new era in the treatment of solid tumors, yet its effectiveness is still constrained and comes with unwanted side effects. The advancement of cutting-edge technology, propelled by gene analysis and manipulation at the molecular scale, shows potential for enhancing these therapies. The advent of genome editing technologies, including CRISPR-Cas9, can greatly augment the efficacy of cancer immunotherapy. This review explores the mechanism of CRISPR-Cas9-mediated genome editing and its wide range of tools. The study focuses on analyzing the effects of CRISPR-induced double-strand breaks (DSBs) on cancer immunotherapy, specifically by gene knockdown or knockin. In addition, the study emphasizes the utilization of CRISPR-Cas9-based genome-wide screening to identify targets, the potential of spatial CRISPR genomics, and the extensive applications and difficulties of CRISPR-Cas9 in fundamental research, translational medicine, and clinical environments. © 2025 Elsevier Ltd

关键词： Cancer immunotherapy CRISPR-Cas9 Double-strand breaks (DSBs) Gene knockdown/knockin Genome editing

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Chitosan-Stabilized Nanoemulsion an Ideal Vehicle for Encapsulation of Microalgal Docosahexaenoic Acid (Dha) with Enhanced Oxidative Stability and Shelf Life for Food Fortification

SSRN

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SSRN 2025年

作者： Mubeena, Sirajdeen Asmath Preetha, Radhakrishnan Department of Food Process Engineering School of Bioengineering Faculty of Engineering and Technology SRM Institute of Science and Technology Tamilnadu Kattankulathur603203 India

TThe current work examines the effect of three distinct emulsifiers such as casein, chitosan, and pectin, on the oxidative stability and physicochemical characteristics of docosahexaenoic acid (DHA) nanoemulsion. Nanoemulsion formulated using chitosan (CHDN) had a greater zeta potential value of 42.2 ± 0.75 mV with a particle size of 122.5 ± 2.5nm initially and maintained electrostatic stability (>30mV) throughout storage (28 days). CHND had a greater encapsulation efficiency of 87.33%, as confirmed by GC-FID. Kalakand (a dairy product) fortified with CHDN retained a higher concentration of DHA (92%) compared to neat DHA oil-incorporated kalakand (20 %) after 10 days of storage. Physio chemical and textural property of CHDN fortified kalakand was significantly higher (P © 2025, The Authors. All rights reserved.

关键词： Chitosan

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Developing a Head-Attached Interface Device for Closed-Loop Transcranial Ultrasound Stimulation in the Mouse Brain

Developing a Head-Attached Interface Device for Closed-Loop ...

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18th International Joint Conference on Biomedical Engineering Systems and Technologies, BIOSTEC 2025

作者： Furukawa, Ryo Murakami, Shuichi Tateno, Takashi Bioengineering and Bioinformatics Graduate School of Information Science and Technology Hokkaido University Kita 14 Nishi 9 Kita-ku Hokkaido Sapporo060-0814 Japan Osaka Research Institute of Industrial Science and Technology 2-7-1 Ayumino Izumi Osaka594-1157 Japan Bioengineering and Bioinformatics Faculty of Information Science and Technology Hokkaido University Kita 14 Nishi 9 Kita-ku Hokkaido Sapporo060-0814 Japan

Transcranial ultrasound stimulation (TUS), which can be used to noninvasively stimulate local and deep brain areas, holds significant promise for clinical applications. However, TUS apparatus is typically constructed with several components, including a relatively large single-element ultrasound (US) transducer, a waveguide, and a driving source. These components pose challenges when conducting experiments with freely moving small animals, especially in the context of wearable devices. Additionally, conventional open-loop stimulation systems do not allow for the simultaneous monitoring of neural activity, which can sometimes result in the overactivation of neural responses. In this study, we developed a head-mounted piezoelectric micromachined ultrasound transducer (PMUT) array with integrated monitoring electrodes to serve as a TUS interface for mice. To determine effective array patterns for optimal US beam profiles, we first conducted beamforming simulations. We then microfabricated the PMUT arrays according to the results of these simulations. Subsequently, we performed electroencephalographic (EEG) recordings to evaluate the potential of TUS in mice while simultaneously monitoring neural activities. Finally, we discuss future applications of a closed loop TUS system in the treatment of brain diseases. © 2025 by SCITEPRESS– Science and technology Publications, Lda.

关键词： Closed loop systems

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Drying Characteristics of Green Pellets Under Hydrogen-Rich Fuel Conditions 154th

Drying Characteristics of Green Pellets Under Hydrogen-Rich ...

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154th Annual Meeting and Exhibition of The Minerals, Metals and Materials Society, TMS 2025

作者： Lin, Kun Su, Zijian Zhang, Yuanbo Ma, Ke Bai, Xiaoguang Fu, Guowei School of Minerals Processing and Bioengineering Central South University Hunan Changsha410083 China Faculty of Materials Metallurgy and Chemistry Jiangxi University of Science and Technology Jiangxi Ganzhou341000 China Technology Center Inner Mongolia Baotou Steel Union Co. Ltd Inner Mongolia Baotou014016 China

ISBN: (纸本)9783031807473

DuetothecombustionofH2,morewatervaporwouldbegeneratedduring the hydrogen-rich fuel roasting, which affects the drying of green pellets. The drying characteristics of green pellets were investigated by simulating hydrogen-rich condi tions with different water vapor contents in this study. The results showed that the water vapor produced during roasting was 1.5 to 4 times higher than that of conven tional fuels when using H2 as fuel. The water vapor concentration in the flue gas of rotary kilns can be 5% to 10%. The water vapor in the drying flue gas would slow down the drying rate of the green pellets. The water vapor content of the drying hot air should be matched to the temperature and pellet moisture under hydrogen-rich operating conditions. When the moisture of green pellets was 8.0%, the water vapor content was 10%, and the dehydration rate of green pellets could reach more than 97% after drying at 300 °C for 8 min. © TheMinerals, Metals & Materials Society 2025.

关键词： Drying characteristics Green pellets Hydrogen Moisture

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