Zoological Research最新文献_第4页

Updated roles of the gut microbiota in exploring shrimp etiology, polymicrobial pathogens, and disease incidence. 肠道微生物群在探索虾病因、多微生物病原体和疾病发病率中的最新作用。

IF 4 1区生物学

Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.158

Jin-Bo Xiong, Hao-Nan Sha, Jiong Chen

{"title":"Updated roles of the gut microbiota in exploring shrimp etiology, polymicrobial pathogens, and disease incidence.","authors":"Jin-Bo Xiong, Hao-Nan Sha, Jiong Chen","doi":"10.24272/j.issn.2095-8137.2024.158","DOIUrl":"10.24272/j.issn.2095-8137.2024.158","url":null,"abstract":"Litopenaeus vannamei is the most extensively cultured shrimp species globally, recognized for its scale, production, and economic value. However, its aquaculture is plagued by frequent disease outbreaks, resulting in rapid and massive mortality. etiological research often lags behind the emergence of new diseases, leaving the causal agents of some shrimp diseases unidentified and leading to nomenclature based on symptomatic presentations, especially in cases involving co- and polymicrobial pathogens. Comprehensive data on shrimp disease statuses remain limited. In this review, we summarize current knowledge on shrimp diseases and their effects on the gut microbiome. Furthermore, we also propose a workflow integrating primary colonizers, \"driver\" taxa in gut networks from healthy to diseased states, disease-discriminatory taxa, and virulence genes to identify potential polymicrobial pathogens. We examine both abiotic and biotic factors (e.g., external and internal sources and specific-disease effects) that influence shrimp gut microbiota, with an emphasis on the \"holobiome\" concept and common features of gut microbiota response to diverse diseases. After excluding the effects of confounding factors, we provide a diagnosis model for quantitatively predicting shrimp disease incidence using disease common-discriminatory taxa, irrespective of the causal agents. Due to the conservation of functional genes used in designing specific primers, we propose a practical strategy applying qPCR-assayed abundances of disease common-discriminatory functional genes. This review updates the roles of the gut microbiota in exploring shrimp etiology, polymicrobial pathogens, and disease incidence, offering a refined perspective for advancing shrimp aquaculture health management.","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A new era of mutation rate analyses: Concepts and methods. 突变率分析的新时代：概念与方法

IF 4 1区生物学

Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.058

Kun Wu, Danqi Qin, Yang Qian, Haoxuan Liu

引用次数: 0

Study of tree shrew biology and models: A booming and prosperous field for biomedical research. 树鼩生物学和模型研究：一个蓬勃发展、欣欣向荣的生物医学研究领域。

IF 4 1区生物学

Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.199

Yong-Gang Yao, Li Lu, Rong-Jun Ni, Rui Bi, Ceshi Chen, Jia-Qi Chen, Eberhard Fuchs, Marina Gorbatyuk, Hao Lei, Hongli Li, Chunyu Liu, Long-Bao Lv, Kyoko Tsukiyama-Kohara, Michinori Kohara, Claudia Perez-Cruz, Gregor Rainer, Bao-Ci Shan, Fang Shen, An-Zhou Tang, Jing Wang, Wei Xia, Xueshan Xia, Ling Xu, Dandan Yu, Feng Zhang, Ping Zheng, Yong-Tang Zheng, Jumin Zhou, Jiang-Ning Zhou

{"title":"Study of tree shrew biology and models: A booming and prosperous field for biomedical research.","authors":"Yong-Gang Yao, Li Lu, Rong-Jun Ni, Rui Bi, Ceshi Chen, Jia-Qi Chen, Eberhard Fuchs, Marina Gorbatyuk, Hao Lei, Hongli Li, Chunyu Liu, Long-Bao Lv, Kyoko Tsukiyama-Kohara, Michinori Kohara, Claudia Perez-Cruz, Gregor Rainer, Bao-Ci Shan, Fang Shen, An-Zhou Tang, Jing Wang, Wei Xia, Xueshan Xia, Ling Xu, Dandan Yu, Feng Zhang, Ping Zheng, Yong-Tang Zheng, Jumin Zhou, Jiang-Ning Zhou","doi":"10.24272/j.issn.2095-8137.2024.199","DOIUrl":"10.24272/j.issn.2095-8137.2024.199","url":null,"abstract":"The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumor necrosis factor α deficiency promotes myogenesis and muscle regeneration. 肿瘤坏死因子α的缺乏可促进肌肉生成和肌肉再生。

IF 4 1区生物学

Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.039

Yu Fu, Jing-Ru Nie, Peng Shang, Bo Zhang, Da-Wei Yan, Xin Hao, Hao Zhang

{"title":"Tumor necrosis factor α deficiency promotes myogenesis and muscle regeneration.","authors":"Yu Fu, Jing-Ru Nie, Peng Shang, Bo Zhang, Da-Wei Yan, Xin Hao, Hao Zhang","doi":"10.24272/j.issn.2095-8137.2024.039","DOIUrl":"10.24272/j.issn.2095-8137.2024.039","url":null,"abstract":"Tumor necrosis factor α (TNFα) exhibits diverse biological functions; however, its regulatory roles in myogenesis are not fully understood. In the present study, we explored the function of TNFα in myoblast proliferation, differentiation, migration, and myotube fusion in primary myoblasts and C2C12 cells. To this end, we constructed TNFα muscle-conditional knockout ( TNFα-CKO) mice and compared them with flox mice to assess the effects of TNFα knockout on skeletal muscles. Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development, enhanced regenerative capacity, and improved exercise endurance compared to flox mice, with no significant differences observed in major visceral organs or skeletal structure. Using label-free proteomic analysis, we found that TNFα-CKO altered the distribution of several muscle development-related proteins, such as Hira, Casz1, Casp7, Arhgap10, Gas1, Diaph1, Map3k20, Cfl2, and Igf2, in the nucleus and cytoplasm. Gene set enrichment analysis (GSEA) further revealed that TNFα deficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling. These findings suggest that TNFα-CKO positively regulates muscle growth and development, possibly via these newly identified targets and pathways.","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

On the evolutionary trail of MagRs. 追踪 MagRs 的进化轨迹。

IF 4 1区生物学

Zoological Research Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.074

Jing Zhang, Yafei Chang, Peng Zhang, Yanqi Zhang, Mengke Wei, Chenyang Han, Shun Wang, Hui-Meng Lu, Tiantian Cai, Can Xie

{"title":"On the evolutionary trail of MagRs.","authors":"Jing Zhang, Yafei Chang, Peng Zhang, Yanqi Zhang, Mengke Wei, Chenyang Han, Shun Wang, Hui-Meng Lu, Tiantian Cai, Can Xie","doi":"10.24272/j.issn.2095-8137.2024.074","DOIUrl":"10.24272/j.issn.2095-8137.2024.074","url":null,"abstract":"Magnetic sense, or termed magnetoreception, has evolved in a broad range of taxa within the animal kingdom to facilitate orientation and navigation. MagRs, highly conserved A-type iron-sulfur proteins, are widely distributed across all phyla and play essential roles in both magnetoreception and iron-sulfur cluster biogenesis. However, the evolutionary origins and functional diversification of MagRs from their prokaryotic ancestor remain unclear. In this study, MagR sequences from 131 species, ranging from bacteria to humans, were selected for analysis, with 23 representative sequences covering species from prokaryotes to Mollusca, Arthropoda, Osteichthyes, Reptilia, Aves, and mammals chosen for protein expression and purification. Biochemical studies revealed a gradual increase in total iron content in MagRs during evolution. Three types of MagRs were identified, each with distinct iron and/or iron-sulfur cluster binding capacity and protein stability, indicating continuous expansion of the functional roles of MagRs during speciation and evolution. This evolutionary biochemical study provides valuable insights into how evolution shapes the physical and chemical properties of biological molecules such as MagRs and how these properties influence the evolutionary trajectories of MagRs.","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improvement in Tol2 transposon for efficient large-cargo capacity transgene applications in cultured cells and zebrafish ( Danio rerio). 改进 Tol2 转座子，以便在培养细胞和斑马鱼（Danio rerio）中高效应用大容量转基因。

IF 4.9 1区生物学

Zoological Research Pub Date : 2024-05-18 DOI: 10.24272/j.issn.2095-8137.2024.026

Pengcheng Wang, Hao Deng, rang xu, Jiulin Du, Rongkun Tao

{"title":"Improvement in Tol2 transposon for efficient large-cargo capacity transgene applications in cultured cells and zebrafish ( Danio rerio).","authors":"Pengcheng Wang, Hao Deng, rang xu, Jiulin Du, Rongkun Tao","doi":"10.24272/j.issn.2095-8137.2024.026","DOIUrl":"https://doi.org/10.24272/j.issn.2095-8137.2024.026","url":null,"abstract":"Most viruses and transposons serve as effective carriers for the introduction of foreign DNA up to 11 kb into vertebrate genomes. However, their activity markedly diminishes with payloads exceeding 11 kb. Expanding the payload capacity of transposons could facilitate more sophisticated cargo designs, improving the regulation of expression and minimizing mutagenic risks associated with molecular therapeutics, metabolic engineering, and transgenic animal production. In this study, we improved the Tol2 transposon by increasing protein expression levels using a translational enhancer ( QBI SP163, ST) and enhanced the nuclear targeting ability using the nuclear localization protein H2B (SHT). The modified Tol2 and ST transposon efficiently integrated large DNA cargos into human cell cultures (H1299), comparable to the well-established super PiggyBac system. Furthermore, mRNA from ST and SHT showed a significant increase in transgene delivery efficiency of large DNA payloads (8 kb, 14 kb, and 24 kb) into zebrafish ( Danio rerio). This study presents a modified Tol2 transposon as an enhanced nonviral vector for the delivery of large DNA payloads in transgenic applications.","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140962062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia. 体内成像显示了异丙酚和七氟醚麻醉期间神经递质动态的同步相关性。

IF 4 1区生物学

Zoological Research Pub Date : 2024-05-18 DOI: 10.24272/j.issn.2095-8137.2023.302

Gao-Lin Qiu, Li-Jun Peng, Peng Wang, Zhi-Lai Yang, Ji-Qian Zhang, Hu Liu, Xiao-Na Zhu, Jin Rao, Xue-Sheng Liu

{"title":"In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia.","authors":"Gao-Lin Qiu, Li-Jun Peng, Peng Wang, Zhi-Lai Yang, Ji-Qian Zhang, Hu Liu, Xiao-Na Zhu, Jin Rao, Xue-Sheng Liu","doi":"10.24272/j.issn.2095-8137.2023.302","DOIUrl":"10.24272/j.issn.2095-8137.2023.302","url":null,"abstract":"General anesthesia is widely applied in clinical practice. However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here, we measured the dynamics of five neurotransmitters, including γ-aminobutyric acid, glutamate, norepinephrine, acetylcholine, and dopamine, in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective. Results revealed that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine increased in the cortex during propofol-induced loss of consciousness. Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Furthermore, the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups. These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain. 全身麻醉剂通过发育中的大脑少突胶质细胞诱发神经毒性。

IF 4 1区生物学

Zoological Research Pub Date : 2024-05-18 DOI: 10.24272/j.issn.2095-8137.2023.413

Wen-Xin Hang, Yan-Chang Yang, Yu-Han Hu, Fu-Quan Fang, Lang Wang, Xing-Hua Qian, Patrick M Mcquillan, Hui Xiong, Jian-Hang Leng, Zhi-Yong Hu

{"title":"General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain.","authors":"Wen-Xin Hang, Yan-Chang Yang, Yu-Han Hu, Fu-Quan Fang, Lang Wang, Xing-Hua Qian, Patrick M Mcquillan, Hui Xiong, Jian-Hang Leng, Zhi-Yong Hu","doi":"10.24272/j.issn.2095-8137.2023.413","DOIUrl":"10.24272/j.issn.2095-8137.2023.413","url":null,"abstract":"General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells. Oligodendrocytes perform essential roles in the central nervous system, including myelin sheath formation, axonal metabolism, and neuroplasticity regulation. They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation, differentiation, and apoptosis. Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes. These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways, but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function. In this review, we summarize the effects of general anesthetic agents on oligodendrocytes. We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatially resolved transcriptomic profiling of placental development in dairy cow. 奶牛胎盘发育的空间分辨率转录组特征分析

IF 4 1区生物学

Zoological Research Pub Date : 2024-05-18 DOI: 10.24272/j.issn.2095-8137.2023.205

Guang-Hui Tan, Shi-Jie Liu, Ming-Le Dou, De-Feng Zhao, Ao Zhang, Heng-Kuan Li, Fu-Nong Luo, Tao Shi, Hao-Ping Wang, Jing-Yuan Lei, Yong Zhang, Yu Jiang, Yi Zheng, Fei Wang

{"title":"Spatially resolved transcriptomic profiling of placental development in dairy cow.","authors":"Guang-Hui Tan, Shi-Jie Liu, Ming-Le Dou, De-Feng Zhao, Ao Zhang, Heng-Kuan Li, Fu-Nong Luo, Tao Shi, Hao-Ping Wang, Jing-Yuan Lei, Yong Zhang, Yu Jiang, Yi Zheng, Fei Wang","doi":"10.24272/j.issn.2095-8137.2023.205","DOIUrl":"10.24272/j.issn.2095-8137.2023.205","url":null,"abstract":"The placenta plays a crucial role in successful mammalian reproduction. Ruminant animals possess a semi-invasive placenta characterized by a highly vascularized structure formed by maternal endometrial caruncles and fetal placental cotyledons, essential for full-term fetal development. The cow placenta harbors at least two trophoblast cell populations: uninucleate (UNC) and binucleate (BNC) cells. However, the limited capacity to elucidate the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of both the molecular and cellular interactions between trophoblast cells and niches, and the molecular mechanisms governing trophoblast differentiation and functionalization. To fill this knowledge gap, we employed Stereo-seq to map spatial gene expression patterns at near single-cell resolution in the cow placenta at 90 and 130 days of gestation, attaining high-resolution, spatially resolved gene expression profiles. Based on clustering and cell marker gene expression analyses, key transcription factors, including YBX1 and NPAS2, were shown to regulate the heterogeneity of trophoblast cell subpopulations. Cell communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the placental microenvironment. Differential analysis of cell trajectories identified a set of genes involved in regulation of trophoblast differentiation. Additionally, spatial modules and co-variant genes that help shape specific tissue structures were identified. Together, these findings provide foundational insights into important biological pathways critical to the placental development and function in cows.","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice. 野生型 HRAS 的过表达促使小鼠从非酒精性脂肪性肝炎发展为肝细胞癌。

IF 4.9 1区生物学

Zoological Research Pub Date : 2024-05-18 DOI: 10.24272/j.issn.2095-8137.2024.002

Chen Ling, Susu Liu, Yuya Wang, Guitao Huo, Yanwei Yang, Nan Xu, Hong Wang, Yong Wu, Yufa Miao, Rui Fu, Yuwei Zhao, Changfa Fan

{"title":"Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice.","authors":"Chen Ling, Susu Liu, Yuya Wang, Guitao Huo, Yanwei Yang, Nan Xu, Hong Wang, Yong Wu, Yufa Miao, Rui Fu, Yuwei Zhao, Changfa Fan","doi":"10.24272/j.issn.2095-8137.2024.002","DOIUrl":"https://doi.org/10.24272/j.issn.2095-8137.2024.002","url":null,"abstract":"Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human HRAS overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0