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Enhancement of porcine in vitro embryonic development through luteolin‑mediated activation of the Nrf2/Keap1 signaling pathway

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Journal of Animal science and Biotechnology 2024年第2期15卷 600-613页

作者： Se-Been Jeon Pil-Soo Jeong Min Ju Kim Hyo-Gu Kang Bong-Seok Song Sun-Uk Kim Seong-Keun Cho Bo-Woong Sim Futuristic Animal Resource&Research Center(FARRC) Korea Research Institute of Bioscience and Biotechnology(KRIBB)Cheongju 28116Republic of Korea department of Animal science College of Natural Resources&Life SciencePusan National UniversityMiryang 50463Republic of Korea department of Animal science and Biotechnology College of Agriculture and Life ScienceChungnam National UniversityDaejeon 34134Republic of Korea department of Functional Genomics University of Science and TechnologyDaejeon 34113Republic of Korea department of Animal science Life and Industry Convergence Research Institute(RICRI)College of Natural Resources&Life SciencePusan National UniversityMiryang 50463Republic of Korea

Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic development.Luteolin(Lut)has been documented for its protective effects against oxidative stress in various studies.However,its specific role in embryonic development remains unexplored.This study aims to investigate the influence of Lut on porcine embryonic development and to elucidate the underlying mechanism.Results After undergoing parthenogenetic activation(PA)or in vitro fertilization,embryos supplemented with 0.5μmol/L Lut displayed a significant enhancement in cleavage and blastocyst formation rates,with an increase in total cell numbers and a decrease in the apoptosis rate compared to the control.Measurements on D2 and D6 revealed that embryos with Lut supplementation had lower ROS levels and higher glutathione levels compared to the control.Moreover,Lut supplementation significantly augmented mitochondrial content and membrane potential.Intriguingly,activation of the Nrf2/Keap1 signaling pathway was observed in embryos supplemented with Lut,leading to the upregulation of antioxidant-related gene transcription levels.To further validate the relationship between the Nrf2/Keap1 signaling pathway and effects of Lut in porcine embryonic development,we cultured PA embryos in a medium supplemented with brusatol,with or without the inclusion of Lut.The positive effects of Lut on developmental competence were negated by brusatol treatment.Conclusions Our findings indicate that Lut-mediated activation of the Nrf2/Keap1 signaling pathway contributes to the enhanced production of porcine embryos with high developmental competence,and offers insight into the mechanisms regulating early embryonic development.

关键词： Luteolin Mitochondrial function Nrf2/Keap1 signaling pathway Oxidative stress Porcine embryo development

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A pipeline to characterize p53 effectors by integrative cistrome and transcriptome analysis in a genetically-defined organoid model

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Genes & Diseases 2024年第2期11卷 512-515页

作者： June-Ha Shin Hwa-Ryeon Kim Jae-Seok Roe department of Biochemistry College of Life Science and BiotechnologyYonsei UniversitySeoul 120-749Republic of Korea

Tumor-protein 53(p53)is a transcription factor(TF)encoded by TP53(Trp53 in mice)and is a master regulator of tumor-suppressive programs'.Importantly,TP53 is the most frequently mutated gene in human cancer,and its loss of function contributes to tumor development,exemplified by variable p53 mutations detected in 50%-75%of pancreatic cancers.2 From these perceptions,a number of targets transcribed by p53 that confer tumor suppression have been identified.Nevertheless,our understanding of how p53 prevents normal cells from initiating tumorigenesis is still incomplete.To complement this limitation,herein,we established a new approach to identify underlying effectors transcribed by p53 in normal physiology.

关键词： incomplete initiating herein

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Applications and grants of the National Natural science Foundation of China's General Program and Young Scientists Fund in immunology research:a 10-year review(2013–2022)

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science China(life sciences) 2024年第6期67卷 1321-1324页

作者： Baoman Li Yanyan Tian Puyue Wang department of life sciences National Natural Science Foundation of ChinaBeijing 100085China

Immunology,a biomedical discipline with an ancient history of maintaining thriving research vitality to date,refers to the study of the structure and function of the immune system of the body,the pathogenesis of immune-related diseases,immunological diagnoses,and prevention mechanisms(National Natural science Foundation of China,2023).Immunological research is the foundation of research in biology,as well as basic and clinical medicine(Kubli et al.,2021).

关键词： prevention Foundation Natural

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Integration of multiple flexible electrodes for realtime detection of barrier formation with spatial resolution in a gut-on-chip system

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Microsystems & Nanoengineering 2024年第1期10卷 105-114页

作者： Mara Lucchetti Gabriel Werr Sofia Johansson Laurent Barbe Léa Grandmougin Paul Wilmes Maria Tenje Luxembourg Centre for Systems Biomedicine(LCSB) University of LuxembourgEsch-sur-Alzette L-4362Luxembourg Division of Biomedical Engineering Department of Materials Science and EngineeringScience for Life LaboratoryUppsala University75121 UppsalaSweden department of life sciences and Medicine Faculty of ScienceTechnology and MedicineUniversity of LuxembourgEsch-sur-Alzette L-4362Luxembourg

In healthy individuals,the intestinal epithelium forms a tight barrier to prevent gut bacteria from reaching blood circulation.To study the effect of probiotics,dietary compounds and drugs on gut barrier formation and disruption,human gut epithelial and bacterial cells can be cocultured in an in vitro model called the human microbial crosstalk(HuMiX)gut-on-a-chip system.Here,we present the design,fabrication and integration of thin-film electrodes into the HuMiX platform to measure transepithelial electrical resistance(TEER)as a direct readout on barrier tightness in realtime.As various aspects of the HuMiX platform have already been set in their design,such as multiple compressible layers,uneven surfaces and nontransparent materials,a novel fabrication method was developed whereby thin-film metal electrodes were first deposited on flexible substrates and sequentially integrated with the HuMiX system via a transfer-tape approach.Moreover,to measure localized TEER along the cell culture chamber,we integrated multiple electrodes that were connected to an impedance analyzer via a multiplexer.We further developed a dynamic normalization method because the active measurement area depends on the measured TEER levels.The fabrication process and system setup can be applicable to other barrier-on-chip systems.As a proof-of-concept,we measured the barrier formation of a cancerous Caco-2 cell line in real-time,which was mapped at four spatially separated positions along the HuMiX culture area.

关键词： barrier system multiple

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Recent progress and future directions of the research on nanoplastic-induced neurotoxicity

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Neural Regeneration Research 2024年第2期19卷 331-335页

作者： Seung-Woo Han Jinhee Choi Kwon-Yul Ryu department of life science University of SeoulSeoulSouth Korea School of Environmental Engineering University of SeoulSeoulSouth Korea

Many types of plastic products,including polystyrene,have long been used in commercial and industrial applications.Microplastics and nanoplastics,plastic particles derived from these plastic products,are emerging as environmental pollutants that can pose health risks to a wide variety of living organisms,including humans.However,it is not well understood how microplastics and nanoplastics affect cellular functions and induce stress responses.Humans can be exposed to polystyrene-microplastics and polystyrene-nanoplastics through ingestion,inhalation,or skin contact.Most ingested plastics are excreted from the body,but inhaled plastics may accumulate in the lungs and can even reach the brain via the nose-to-brain route.Small-sized polystyrene-nanoplastics can enter cells by endocytosis,accumulate in the cytoplasm,and cause various cellular stresses,such as inflammation with increased pro-inflammatory cytokine production,oxidative stress with generation of reactive oxygen species,and mitochondrial dysfunction.They induce autophagy activation and autophagosome formation,but autophagic flux may be impaired due to lysosomal dysfunction.Unless permanently exposed to polystyrene-nanoplastics,they can be removed from cells by exocytosis and subsequently restore cellular function.However,neurons are very susceptible to this type of stress,thus even acute exposure can lead to neurodegeneration without recovery.This review focuses specifically on recent advances in research on polystyrene-nanoplastic-induced cytotoxicity and neurotoxicity.Furthermore,in this review,based on mechanistic studies of polystyrene-nanoplastics at the cellular level other than neurons,future directions for overcoming the negative effects of polystyrene-nanoplastics on neurons were suggested.

关键词： autophagy cellular stress cytotoxicity endocytosis exocytosis inflammation microplastics nanoplastics neurotoxicity oxidative stress polystyrene

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Gut flora in multiple sclerosis:implications for pathogenesis and treatment

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Neural Regeneration Research 2024年第7期19卷 1480-1488页

作者： Weiwei Zhang Ying Wang Mingqin Zhu Kangding Liu Hong-Liang Zhang department of Neurology the First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina department of life sciences National Natural Science Foundation of ChinaBeijingChina

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

关键词： gut flora gut-brain axis multiple sclerosis pathogenesis treatment

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How variable progenitor clones construct a largely invariant neocortex

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National science Review 2024年第1期11卷 129-144页

作者： Zhongfu Shen Jiajun Yang Qiangqiang Zhang Kuiyu Wang Xiaohui Lv Xiaolin Hu Jian Ma Song-Hai Shi New Cornerstone science Laboratory IDG/McG overn Institute for Brain Research Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University department of Computer sciences Tsinghua University College of life sciences Nankai University Chinese Institute for Brain Research

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors(RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

关键词： neocortex radial glial progenitor intermediate progenitor neurogenesis clonal variability layer formation

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Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

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中华医学杂志(英文版) 2024年第10期137卷 1207-1217页

作者： Pan Tianzhong Ding Peng Huang Aijie Tang Baolin Song Kaidi Sun Guangyu Wu Yue Yang Shiying Chen Xingchi Wang Dongyao Zhu Xiaoyu department of Hematology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China Anhui Provincial Key Laboratory of Blood Research and Applications Hefei Anhui China Blood and Cell Therapy Institute Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China Division of life sciences and Medicine University of Science and Technology of China Hefei Anhui China The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China

Background: With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods: A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results: The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year (F = 4.684,P = 0.039 andF = 5.583,P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93;P = 0.031).Conclusions: Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

关键词： Umbilical cord blood transplantation Graft-versus-host disease Immune reconstitution Double negative T Hematological Malignancies Treg cell Breg cell

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Development and validation of a nomogram model for predicting the risk of pre-hospital delay in patients with acute myocardial infarction

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World Journal of Cardiology 2024年第2期16卷 80-91页

作者： Jiao-Yu Cao Li-Xiang Zhang Xiao-Juan Zhou department of Cardiology The First Affiliated Hospital of USTCDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina

BACKGROUND Acute myocardial infarction(AMI)is a severe cardiovascular disease caused by the blockage of coronary arteries that leads to ischemic necrosis of the myocardium.Timely medical contact is critical for successful AMI treatment,and delays increase the risk of death for patients.Pre-hospital delay time(PDT)is a significant challenge for reducing treatment times,as identifying high-risk patients with AMI remains difficult.This study aims to construct a risk prediction model to identify high-risk patients and develop targeted strategies for effective and prompt care,ultimately reducing PDT and improving treatment outcomes.AIM To construct a nomogram model for forecasting pre-hospital delay(PHD)likelihood in patients with AMI and to assess the precision of the nomogram model in predicting PHD risk.METHODS A retrospective cohort design was employed to investigate predictive factors for PHD in patients with AMI diagnosed between January 2022 and September 2022.The study included 252 patients,with 180 randomly assigned to the development group and the remaining 72 to the validation group in a 7:3 ratio.Independent risk factors influencing PHD were identified in the development group,leading to the establishment of a nomogram model for predicting PHD in patients with AMI.The model's predictive performance was evaluated using the receiver operating characteristic curve in both the development and validation groups.RESULTS Independent risk factors for PHD in patients with AMI included living alone,hyperlipidemia,age,diabetes mellitus,and digestive system diseases(P<0.05).A characteristic curve analysis indicated area under the receiver operating characteristic curve values of 0.787(95%confidence interval:0.716–0.858)and 0.770(95%confidence interval:0.660-0.879)in the development and validation groups,respectively,demonstrating the model's good discriminatory ability.The Hosmer–Lemeshow goodness-of-fit test revealed no statistically significant disparity between the anticipated and observed incidence of PHD in both

关键词： Pre-hospital delay Acute myocardial infarction Risk prediction Nomogram

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Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes

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National science Review 2024年第1期11卷 161-173页

作者： Feng Xue Fei Li Ke-ming Zhang Lufeng Ding Yang Wang Xingtao Zhao Fang Xu Danke Zhang Mingzhai Sun Pak-Ming Lau Qingyuan Zhu Pengcheng Zhou Guo-Qiang Bi Institute of Artiflcial Intelligence Hefei Comprehensive National Science Center department of Precision Machinery and Precision Instruments University of Science and Technology of China Hefei National Laboratory for Physical sciences at the Microscale University of Science and Technology of China Interdisciplinary Center for Brain Information the Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Faculty of life and Health sciences Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences School of life sciences University of Science and Technology of China Institute of Semiconductors Chinese Academy of Sciences department of Modern life sciences and Biotecnology Xiongan Institute of Innovation Xiongan New Area Shenzhen-Hong Kong Institute of Brain science-Shenzhen Fundamental Research Institutions Suzhou Institute for Advanced Research University of Science and Technology of China

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the equipment.Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in mice.Proof-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

关键词： miniature microscope multiple sites calcium imaging multimodal integration hippocampus

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