Biological Research最新文献

{"title":"Role and mechanisms of vascular smooth muscle cell phenotypic transition in diabetic macrovascular complications.","authors":"Qiyuan Yao, Hanyu Liu, Xueru Wang, Zehua Zhang, Hongyan Xie, Chunguang Xie, Hong Gao","doi":"10.1186/s40659-025-00665-8","DOIUrl":"10.1186/s40659-025-00665-8","url":null,"abstract":"<p><p>Diabetic macrovascular complications, as one of the leading causes of mortality in diabetic patients, are characterized by insidious onset and high residual risk. Effective prevention and treatment of diabetic macrovascular injury remain critical clinical challenges, necessitating the development of novel therapeutic strategies targeting this complication. Although recent studies have demonstrated that vascular remodeling driven by the phenotypic transition of vascular smooth muscle cells (VSMCs) plays a pivotal role in this process, and increasing attention has been paid to the metabolic pathways and mechanosensitive signaling pathways of VSMCs, the underlying molecular mechanisms remain incompletely elucidated. This review summarizes metabolic reprogramming in VSMCs in diabetes and its impact on vascular remodeling systematically, with a focus on elucidating the core mechanisms of endothelial-VSMC crosstalk, pathological characteristics of VSMCs phenotypic transition during different stages of atherosclerosis (AS), and potential diversified strategies such as the application of microRNAs, extracellular vesicle targeting techniques, and targeted protein regulation. Current evidence indicates that precise modulation of the metabolic-mechanical coupling network in VSMCs can significantly attenuate the progression of atherosclerotic plaques and enhance plaque stability. However, clinical translation remains challenged by insufficient targeting specificity and mechanistic complexity. Future studies should integrate multi-omics technologies with biomimetic models to further optimize therapeutic strategies.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"8"},"PeriodicalIF":4.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12870442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INO80 regulates promoter-associated R-loops to coordinate transcription and maintain genome stability in embryonic stem cells.","authors":"Hoseong Lim, Ohbeom Kwon, Hyeonwoo La, Hyeonji Lee, Heeji Lee, Jeong-Tae Do, Hyuk Song, Youngsok Choi, Kwonho Hong","doi":"10.1186/s40659-025-00666-7","DOIUrl":"10.1186/s40659-025-00666-7","url":null,"abstract":"","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"7"},"PeriodicalIF":5.4,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of pigment epithelium-derived factors on H₂O₂-induced oxidative damage and melanin synthesis in Melan-a cells.","authors":"Yunli Cui, Fuhao Ye, Zengyao Hou, Guohao Li, Luyao Li, Hongxia Zhao, Dongfang Hu, Zhihong Yin, Lingli Chen, Hongmei Ning, Yaming Ge, Quanhai Pang","doi":"10.1186/s40659-025-00657-8","DOIUrl":"10.1186/s40659-025-00657-8","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have demonstrated that oxidative stress and melanogenesis are regulated by the Wnt/β-catenin signaling pathway. However, the precise mechanism by which the PEDF/Wnt/β-catenin axis modulates apoptosis and melanogenesis remains unclear.</p><p><strong>Methods: </strong>Cell viability and mortality rates were assessed using CCK-8 assays and lactate dehydrogenase (LDH) release assays. Mitochondrial ultrastructural changes were analyzed by transmission electron microscopy (TEM). Changes in the mitochondrial membrane potential (ΔΨm) were assessed using the JC-1 fluorescent probe. The effects of PEDF on protein and gene expression were evaluated by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>As the concentration of H₂O₂ increased, the cell survival rate decreased, which activated the Wnt/β-catenin signaling pathway and increased the apoptosis rate and melanin production. PEDF reversed the H₂O₂-induced decrease in cell viability and increase in mortality rate in Melan-a cells while ameliorating the impairment of the mitochondrial membrane potential. PEDF ameliorated H₂O₂-induced protein damage and lipid peroxidation and reduced apoptosis in Melan-a cells. PEDF treatment significantly decreased the protein expression levels of β-catenin, Wnt3a, and Dvl2 (P < 0.05) and reduced the protein levels of Bax and Caspase-3 (P < 0.01) in H₂O₂- and BML-284-treated Melan-a cells. Furthermore, PEDF significantly reduced the H₂O₂- and BML-284-induced increases in the MITF and TYR protein levels (P < 0.01).</p><p><strong>Conclusions: </strong>These results suggest that PEDF can reduce H₂O₂-induced oxidative damage and melanin production in Melan-a cells by inhibiting the activation of Wnt/β-catenin signaling pathway activation. These findings provide a theoretical basis for human oxidative stress and pigment deposition-related diseases.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"58 1","pages":"78"},"PeriodicalIF":4.6,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12751373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145853355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daphnetin alleviates unexplained recurrent spontaneous abortion by regulating the NR4A1/BACH2 axis in mice.","authors":"Zhiqin Zhang, Jun Tan, Xingwu Wu, Xin Li, Peipei Liu, Liyun Cao, Shenggen Long","doi":"10.1186/s40659-025-00658-7","DOIUrl":"10.1186/s40659-025-00658-7","url":null,"abstract":"<p><strong>Background: </strong>Daphnetin has demonstrated various pharmacological activities. The current study evaluated the potential of daphnetin in alleviating unexplained recurrent spontaneous abortion (URSA) and explored underlying mechanisms.</p><p><strong>Methods: </strong>Mice with URSA were gavaged with 1 mg/kg, 10 mg/kg, and 20 mg/kg of daphnetin, or infected with adeno-associated viruses harboring knockdown of NR4A1 or overexpression of BACH2 before modeling. Human peripheral blood T lymphocytes were induced into CD4⁺ T cells, followed by lentivirus infection and daphnetin treatment. The influence of daphnetin on CD4⁺ T cell viability and Treg and Th17 cell differentiation in cells was analyzed. The concentrations of Treg cells-associated cytokines (TGF-β, IL-10) and Th17 cells-associated cytokines (IL-17, IL-23) in the supernatants of CD4⁺ T cells were assessed. The regulation of NR4A1 on BACH2 was analyzed by ChIP and dual-luciferase assays.</p><p><strong>Results: </strong>Daphnetin resulted in fewer immature, resorbed, or dead embryos in mice with URSA, with the most pronounced therapeutic effect of 10 mg/kg. Daphnetin attenuated decidual hemorrhage, with a gain in the percentage/number of Treg cells and a loss of the percentage/number of Th17 cells in the spleen and decidual tissues. Daphnetin enhanced the expression of FoxP3, TGF-β, and IL-10, and suppressed the expression of RORγt, IL-17, IL-23, and the contents of TNF-α, IL-6, and IL-1β in CD4⁺ T cells. Overexpression of BACH2 further alleviated URSA deterioration caused by NR4A1 knockdown. Daphnetin mediated the transcriptional activation of BACH2 by upregulating NR4A1.</p><p><strong>Conclusions: </strong>Upregulation of NR4A1 by daphnetin mediates BACH2 transcription and Th17/Treg cell homeostasis to improve URSA.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"58 1","pages":"77"},"PeriodicalIF":4.6,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12750638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145854413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial and lysosomal dysfunctions might be involved in the pathogenesis of the CACNA1A-related neurodevelopmental disorders according to in vitro studies.","authors":"Miriam Kessi, Langui Pan, Baiyu Chen, Li Yang, Lifen Yang, Olumuyiwa A Bamgbade, Guoli Wang, Jing Peng, Fei Yin, Fang He","doi":"10.1186/s40659-025-00655-w","DOIUrl":"10.1186/s40659-025-00655-w","url":null,"abstract":"<p><p>BACKGROUND: CACNA1A variants are associated with severe neurodevelopmental disorders (NDDs), but the underlying mechanisms remain unclear. Our goal was to investigate the molecular mechanisms through which these variants lead to intellectual disability (ID), autism spectrum disorder (ASD), epilepsy, and ataxia. METHODS: Clinical information was collected from six pediatric patients. Molecular experiments were performed on transfected human embryonic kidney and Chinese hamster ovary cells to study the effect of these variants on mitochondrial and lysosomal function. RT-qPCR, Western blot, apoptosis assay, mitochondrial and lysosomal tracker fluorescence intensity, and mitochondrial calcium concentration tests were performed. Additionally, we examined the levels of reactive oxygen species (ROS), adenosine triphosphate (ATP), and mitochondrial enzymes and copy numbers. RESULTS: We identified six variants that downregulated CACNA1A mRNA: p.D1644N, p.Y62C, p.G701R, p.R279C, p.R1664Q, and p.L1422Sfs*8. Five variants down-regulated Cav2.1 protein expression, whereas, the p.R279C variant up-regulated it. All variants led to dysfunctions in the autophagy-lysosomal system: p.D1644N, p.R279C, and p.G701R variants blocked the fusion of autophagosomes and lysosomes while p.Y62C, p.R1664Q, and p.L1422Sfs*8 variants displayed increased lysosomal expression. The p.Y62C, p.G701R, p.R279C, p.R1664Q, and p.L1422Sfs*8 variants exhibited defective autophagy. The p.Y62C and p.D1644N variants disrupted mitochondrial function by downregulating mitochondrial enzyme activities and ATP levels, as well as by upregulating mitochondrial copy numbers, calcium levels, and ROS levels. Furthermore, the p.Y62C variant increased mitochondrial expression, fusion, and fission. In contrast, the p.D1644N variant decreased mitochondrial expression, fusion, fission, and mitophagy. The p.G701R, p.R279C, and p.R1664Q variants also interrupted mitochondrial function. These variants down-regulated mitochondrial enzyme activities, fusion and fission, the mitophagy process, and ATP levels while up-regulating mitochondrial copy numbers and ROS levels. The p.L1422Sfs*8 variant increased the expression, fusion and fission of mitochondrial proteins, while decreasing mitochondrial calcium levels and the mitophagy process. The p.R279C variant increased mitochondrial expression and calcium levels while enhancing apoptosis. The p.G701R variant decreased mitochondrial expression and calcium levels while enhancing apoptosis. The p.R1664Q variant increased mitochondrial calcium levels and enhanced apoptosis without changing mitochondrial expression. CONCLUSIONS: CACNA1A variants may alter mitochondrial and lysosomal function, resulting in the development of NDDs. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"76"},"PeriodicalIF":5.4,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12751537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insect neuropeptides as agents for pest control: potential and challenges.","authors":"Natalia Konopińska, Szymon Chowański, Jan Lubawy, Paweł Marciniak, Karolina Walkowiak-Nowicka, Guy Smagghe, Arkadiusz Urbański","doi":"10.1186/s40659-025-00651-0","DOIUrl":"10.1186/s40659-025-00651-0","url":null,"abstract":"<p><p>Chemical insecticides play a crucial role in securing global food production but have also caused serious environmental and health problems due to their persistence and low target specificity. In response, insect neuropeptides, which are biological macromolecules that act as key regulators of development, metabolism, reproduction, and behavior, are being explored as potential environmentally friendly alternatives for pest control. This review evaluates the prospects and limitations of using neuropeptides and their synthetic analogues as bioinsecticides. We discuss their mechanisms of action, challenges in increasing biostability, and the risks of affecting nontarget species. Strategies to improve, introduce and increase their applicability usage include peptide modification, targeted delivery systems, and the use of molecular techniques such as RNA interference (RNAi) and CRISPR-Cas9 to disrupt neuropeptide signaling pathways with high specificity. Advances in omics technologies and artificial intelligence are accelerating the discovery and design of novel neuropeptide-based agents. Nonetheless, regulatory challenges, high production costs, limited ecological impact data, and the potential for resistance development remain key obstacles. The integration of neuropeptide-based approaches with existing pest control methods, particularly within genetically modified crops and integrated pest management (IPM), could enhance both efficacy and environmental sustainability. Although the direct application of neuropeptides is still limited, targeting neuropeptide-related genes appears to be a promising and practical direction for the future of biological pest control.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"6"},"PeriodicalIF":5.4,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of HLA-ABC allele groups in a cohort of Chilean rheumatoid arthritis patients and healthy individuals.","authors":"Miqueas Jaime, Lucero Toro, Constanza Varela-Villarroel, Darly Montano-Bruno, Bárbara Pesce, Daniela Schneider, Lilian Soto, Francisca Bozán, Óscar Neira, María C Cuéllar-Gutiérrez, Consuelo Arroyo, Guido Rivera, Eduard Palou, Diego Catalán, Jaxaira Maggi, Juan C Aguillón","doi":"10.1186/s40659-025-00663-w","DOIUrl":"10.1186/s40659-025-00663-w","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid Arthritis (RA) is an autoimmune disease in which HLA-DRB1 alleles encoding the \"Shared Epitope\" (SE), located in the β-chain of class II HLA-DR molecules, constitute the main genetic risk factor. However, there is scarce information about the role of HLA class I genes (HLA-ABC) in RA susceptibility. The present work aimed to evaluate the distribution of HLA-ABC allele groups in a cohort of Chilean RA patients and healthy subjects (HS), and to explore the influence of HLA-DRB1 SE alleles on this distribution.</p><p><strong>Results: </strong>135 RA patients and 122 HS were genotyped for HLA-ABC. The most frequent allele groups were HLA-A*02 (24.0%), HLA-B*39.1 (14.2%), and HLA-C*07 (24.7%) for RA patients, and HLA-A*02 (31.5%), HLA-A*24 (12.8%) and HLA-C*07 (17.7%) for HS. RA patients presented a significantly higher frequency of HLA-C*07 (p = 0.0015) and HLA-B*39.1 (p = 0.037) allele groups compared to HS. After applying the Bonferroni correction, the significant difference remained only for the HLA-C*07 allele group (p = 0.015). In a subset of RA patients (n = 60), positive for HLA-DRB1 SE alleles, the most frequent HLA-ABC allele groups were HLA-A*02 (0-33.3%), HLA-B*39.1 (0-16.7%), and HLA-C*07 (22.2-60.0%), whereas HLA-B*39.2 and HLA-B*52 were the least frequent ones. Overall, HLA-C*07 was the most frequent allele group across RA patients carrying HLA-DRB1 SE alleles.</p><p><strong>Conclusions: </strong>The HLA-C*07 allele group shows a significantly higher presence in RA patients compared to HS. In contrast, the distribution of most other HLA-ABC allele groups in this cohort displays a similar frequency between RA patients and HS, consistent with data from different populations.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"3"},"PeriodicalIF":4.6,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12814593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145826778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproductive physiological impacts of high ambient temperature on animals: the impaired testicular function and compromised sperm quality in C57BL/6 mice.","authors":"Yun Ren, Kaixuan Zhang, Mengjiao Zhang, Yingying Xia, Yifeng Zhang, Jiqi Lu","doi":"10.1186/s40659-025-00662-x","DOIUrl":"10.1186/s40659-025-00662-x","url":null,"abstract":"<p><p>BACKGROUND: Global warming poses one of the most formidable challenges confronting the contemporary world, exerting extensive and profound impacts on both natural ecosystems and human society. Nevertheless, the detrimental effects of elevated temperatures on reproductive system in animals and humans remains elusive. METHODS: In this study, C57BL/6 mice were exposed to high ambient temperatures (HAT). Subsequently, the testes and sperm parameters of the mice were evaluated following the exposure. RESULTS: The HAT mice had significantly lower weight, food and water intake than those in the control group. The weight of testis and epididymis was significantly lower in the HAT group. The HAT group showed significant reductions in seminiferous tubule area, spermatogenic epithelium area, and seminiferous epithelium thickness. The HAT group exhibited significantly reduced sperm density, viability, and plasma membrane integrity rate. The HAT group exhibited a significantly elevated rate of sperm malformation. Moreover, the expression levels of Dnah8 and Dnah17, two genes associated with Multiple Morphological Abnormalities of the Flagella (MMAF), were markedly reduced in the HAT group. The proportion of TUNEL-positive cells significantly increased in the HAT group. Furthermore, there was a significant upregulation in mRNA expression levels of apoptotic genes Caspase-3 and Bax in the HAT group. Conversely, there was a notable decrease in mRNA expression level of anti-apoptotic gene Bcl-2. The concentration of MDA in the HAT group was significantly higher, while SOD activity and T-AOC were significantly lower. CONCLUSIONS: Therefore, it can be inferred that elevated air temperature leads to multi-layered damage to animal reproduction. This suggests that extreme high temperatures resulting from climate warming will have a detrimental impact on animal reproduction. This study provides support for elucidating the mechanism underlying the reproductive effects of high temperature. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"5"},"PeriodicalIF":5.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12836821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted inhibin B synthesis due to Sox9 hyper-palmitoylation in Sertoli cells impairs spermatogenesis via paracrine effects.","authors":"Yijian Xiang, Yao Xu, Jing Zhang, Miao Zhu, Zhaowanyue He, Ming Zang, Rujun Ma, Li Chen, Zhou Li, Tian Du, Liangyu Yao, Kuan Liang, Jiaming Shen, Shanmeizi Zhao, Jun Jing, Xie Ge, Bing Yao","doi":"10.1186/s40659-025-00661-y","DOIUrl":"10.1186/s40659-025-00661-y","url":null,"abstract":"<p><strong>Background: </strong>Male subfertility is a global health concern, with spermatogenic dysfunction being a critical cause. Abnormally high level of palmitic acid (PA), a main component of dietary saturated fatty acid, has been reported to be implicated in the spermatogenic dysfunction, accompanied with a decrease of inhibin B (INHB). However, the mechanism underlying PA-induced downregulation of INHB, and the specific function of INHB in the spermatogenesis microenvironment, remain unclear. Since PA is the main substrate of palmitoylation, a common post-translational lipid modification, we investigated the role of palmitoylation in INHB synthetic defects and subsequent dyszoospermia induced by PA in this study.</p><p><strong>Methods: </strong>Mice were treated with PA for 30 days to establish a high PA model, and a palmitoylation inhibitor 2-bromopalmitate (2BP) was used for spermatogenesis rescuing. Concentrations and motilities of sperms in the cauda epididymides were analyzed, and pathological examinations were performed to assess spermatogenic function. Hormone levels were detected using ELISA. Primary mouse Sertoli cells and TM4 Sertoli cell line were used for in vitro exploration of mechanisms. Acyl biotin exchange assay was used to explore protein palmitoylation. Co-culture of TM4 and GC1 cells was used to explore the effects of Sertoli cell-secreted INHB on spermatogonia in a paracrine manner.</p><p><strong>Results: </strong>In this study, we found that excessive PA downregulates testicular INHB levels by suppressing expression of its βB subunit (InhβB) in Sertoli cells, with hyper-palmitoylation of the transcription factor SRY-box containing gene 9 (Sox9) serving as a key regulatory node in this process. We further identified the palmitoyl transferase ZDHHC16 as the primary enzyme responsible for PA-induced Sox9 hyper-palmitoylation. Furthermore, INHB was shown to promote spermatogonial proliferation and differentiation in a paracrine manner within the spermatogenic microenvironment, thereby mediating the modulation of spermatogenesis by palmitoylation in Sertoli cells.</p><p><strong>Conclusion: </strong>Overall, this study demonstrated that INHB synthesis can be suppressed by PA-induced hyper-palmitoylation of Sox9, and decreased secretion of INHB by Sertoli cells directly leads to spermatogenic dysfunction in the testis microenvironment. These findings highlight Sox9 palmitoylation as a candidate target for treatment of dyszoospermia accompanied with dyslipidemia, and underscore the critical role of INHB in regulating spermatogenesis within the testicular microenvironment.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"4"},"PeriodicalIF":4.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a high-yield Rabbit line for enhanced animal pharming.","authors":"Jun Song, Dongshan Yang, Lingjie Kong, Li-Kuang Tsai, Jifeng Zhang, Y Eugene Chen, Ruby Yanru Tsai, Jie Xu","doi":"10.1186/s40659-025-00653-y","DOIUrl":"10.1186/s40659-025-00653-y","url":null,"abstract":"<p><p>Animal pharming involves producing recombinant protein drugs using transgenic animals. The United States Food and Drug Administration (FDA) has approved certain drugs produced in the milk of transgenic Rabbits. Traditionally, these pharming Rabbits have been developed using conventional transgenic technology, which often results in an unpredictable success rate, uncontrollable transgene insertion sites, varying copy numbers, and generally low recombinant protein yields, typically 1-2 g/L or lower. We hypothesized that utilizing the promoter of a native major milk protein gene to drive transgene expression could significantly enhance yield. To test this, we developed a rabbit line that expresses tdTomato under the control of the CSN2 gene promoter, responsible for encoding β-casein, the most abundant protein in Rabbit milk. We successfully generated knock-in founder Rabbits using CRISPR/Cas9-mediated knock-in technology, augmented by the homology-directed repair (HDR)-promoting small molecule RS-1. These founder Rabbits were able to transmit the knock-in allele to their offspring, producing both heterozygous and homozygous tdTomato knock-in Rabbits. Remarkably, the recombinant protein yield reached 15-20 g/L in the milk of homozygous animals. Our work demonstrates a promising strategy to enhance recombinant protein production in Rabbit pharming.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"58 1","pages":"73"},"PeriodicalIF":4.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12696889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}