ZOOLOGICAL RESEARCH
·
2025
·Vol. 46
·期 4
·733
·
IF 4.7
Bao-Guo Shen,Yuan Wen,Sheng-Jian Lu,Hong-Yuan Wei,Shu-Rui Huang,Guang-Ming Zhou,Wen-Tao Yan,Wen-Can Wu,Yi-Kui Zhang
In adult mammals, optic nerve injury leads to irreversible vision loss due to its extremely limited regenerative capacity. In contrast, adult zebrafish possess a robust capacity for spontaneous visual system regeneration, although the spatiotemporal coordination of recovery across the retina, optic nerve, and brain remains poorly understood. In the present study, the regenerative dynamics following optic nerve transection were systematically characterized in adult zebrafish over a 5 week period using hematoxylin-eosin staining, immunohistochemistry, transmission electron microscopy, single-cell RNA sequencing, and optokinetic response (OKR) behavioral assessments. At 1 week post-injury (1 wpi), retinal ganglion cell depletion was evident but showed significant recovery by 2 wpi. Concurrently, the injured optic nerve displayed a marked increase in diameter and cell number at 2 wpi, including widespread expression of proliferating cell nuclear antigen, consistent with heightened proliferative activity. Single-cell transcriptomic profiling at 2 wpi revealed five principal cell populations: fibroblasts, mural cells, immune cells, mature oligodendrocytes, and myelin-forming oligodendrocytes. By 4–5 wpi, remyelination within the optic nerve and re-establishment of synaptic architecture in the optic tectum were strongly correlated with functional restoration of OKR behavior. These findings provide a comprehensive spatiotemporal framework of visual pathway regeneration in zebrafish, establishing a valuable model for elucidating conserved mechanisms of neural repair with translational potential for human vision restoration.
研究领域:
神经再生
·
发育生物学
·
分子神经科学
·
视觉系统
·
转化医学研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
GENOMICS
·
2024
·
IF 3.4
Jiongxue Chen,Jiatian Xie,Fuyin Deng,Jinhua Cai,Sitai Chen,Xingrong Song,Shangzhou Xia,Qingyu Shen,Xinying Guo,Yamei Tang
The significance of the adaptive immune response in Alzheimer's disease (AD) is increasingly recognized. We analyzed scRNA-Seq data from AD patients, revealing a notable rise in CD4 cytotoxic T cells (CD4-CTLs) in peripheral blood mononuclear cells (PBMCs), validated in vivo and in vitro. This rise correlates with cognitive decline in AD patients. We also identified transcription factors TBX21 and MYBL1 as key drivers of CD4-CTL expansion. Further analyses indicate these cells are terminally differentiated, showing clonal expansion, metabolic changes, and unique communication patterns. Mendelian randomization identified risk genes SRGN and ITGB1, suggesting their genetic regulation in CD4-CTLs may contribute to AD. To summarize, our findings characterize the expansion of CD4-CTLs in the PBMCs of AD patients, providing valuable understanding into the possible mechanisms involved in the expansion of CD4-CTLs in AD.
研究领域:
神经科学
·
免疫学
·
基因组学
·
转化医学
✓ 已验证
DOI
PubMed
高影响因子
iScience
·
2022
·
IF 6.107
Junzhe Zhang,Wenxue Lei,Yixuan Meng,Chengqian Zhou,Baihong Zhang,Jun Yuan,Min Wang,Dongqing Xu,Xiangchun Meng,Wenli Chen
Summary Huanglongbing ( HLB ) is a devastating disease of citrus, which is mostly caused by Candidatus Liberibacter asiaticus (C Las ). To realize the specific application of nano-transgenic technology in HLB, AuNPs-PEI (Gold Nanoparticles-Polyethylenimine) was used to carry foreign genes into the leaves of periwinkle ( Catharanthus roseus ) by infiltration. Here, we demonstrated that NPR1-GFP protein expression was observed from the 12th hour to the 10th day after infiltrating AuNPs-PEI-pNPR1 ( Arabidopsis thaliana nonexpressor of pathogenesis-related gene 1 )-GFP. Fluorescence of mCherry was observed 6 h after AuNPs-PEI-pNLS (nuclear localization signal sequence)-mCherry infiltration and fluorescence of FAM was observed in the nucleus 4 h after AuNPs-PEI-FAM-siRNA NPR1 infiltration. In addition, NPR1-GFP expression in C Las-infected periwinkle leaves was significantly higher than that in healthy periwinkle leaves after infiltration. Our work confirmed that the expression of exogenous NPR1-GFP could reduce the C Las titers by promoting the expression of PR ( pathogenesis related ) genes and ICS ( isochorismate synthase ) gene.
研究领域:
植物学
·
遗传学
·
分子生物学
·
植物病理学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 7
·1986-1993
·
IF 5.831
Wenxin Zhang,Yang Zhou,Xudong Li,Xin Xu,Yongbing Chen,Rongying Zhu,Lichen Yin
As one of the intractable challenges in the clinic, the treatment of acute liver failure (ALF) is limited due to high mortality and resource cost. RNA interference (RNAi) provides a new modality for the anti-inflammatory therapy of ALF, while its therapeutic efficacy is greatly hampered by the lack of effective carriers to cooperatively overcome the various systemic barriers. Herein, we developed macrophage-targeting and reactive oxygen species (ROS)-responsive polyplexes to enable efficient systemic delivery of TNF-α siRNA (siTNF-α) to attenuate hepatic inflammation in mice bearing ALF. Se-PEI, obtained from the cross-linking of 600 Da polyethylenimine (PEI) via the ROS-responsive diselenide bond, was developed to condense siTNF-α, and the obtained polyplexes were further coated with carboxylated mannan (Man-COOH). Man-COOH coating allowed active targeting of polyplexes to macrophages with over-expressed mannose receptors (MRs), and it shielded the surface positive charges to enhance the serum stability of polyplexes. Se-PEI could be degraded by ROS in inflammatory macrophages to promote intracellular siRNA release to potentiate the gene knockdown efficiency, and in the meantime reduce the material cytotoxicity associated with high molecular weight. As such, i.v. injected Man-COOH/Se-PEI/siTNF-α polyplexes afforded notable TNF-α silencing by ∼80% in inflamed liver tissues at 500 μg siRNA per kg, and notably reduced serum TNF-α levels to achieve potent anti-inflammatory performance against ALF.
研究领域:
药理学
·
纳米技术
·
分子生物学
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
CELL DEATH AND DIFFERENTIATION
·
2023
·Vol. 30
·期 5
·1260-1278
·
IF 12.4
Sun Ge,Wei Yuntao,Zhou Baosheng,Wang Manlin,Luan Ruina,Bai Yu,Li Hao,Wang Shan,Zheng Dantong,Wang Chunyu,Wang Shengli,Zeng Kai,Liu Shuchang,Lin Lin,He Mingcong,Zhang Qiang,Zhao Yue
The estrogen receptor alpha (ERα) signaling pathway is a crucial target for ERα-positive breast cancer therapeutic strategies. Co-regulators and other transcription factors cooperate for effective ERα-related enhancer activation. Recent studies demonstrate that the transcription factor CTCF is essential to participate in ERα/E2-induced enhancer transactivation. However, the mechanism of how CTCF is achieved remains unknown. Here, we provided evidence that BAP18 is required for CTCF recruitment on ERα-enriched enhancers, facilitating CTCF-mediated chromatin accessibility to promote enhancer RNAs transcription. Consistently, GRO-seq demonstrates that the enhancer activity is positively correlated with BAP18 enrichment. Furthermore, BAP18 interacts with SMARCA1/BPTF to accelerate the recruitment of CTCF to ERα-related enhancers. Interestingly, BAP18 is involved in chromatin accessibility within enhancer regions, thereby increasing enhancer transactivation and enhancer-promoter looping. BAP18 depletion increases the sensitivity of anti-estrogen and anti-enhancer treatment in MCF7 cells. Collectively, our study indicates that BAP18 coordinates with CTCF to enlarge the transactivation of ERα-related enhancers, providing a better understanding of BAP18/CTCF coupling chromatin remodeling and E-P looping in the regulation of enhancer transcription.
研究领域:
癌症生物学
·
分子生物学
·
转录调控
·
染色质结构
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Yu Gaoxiang,Ding Jian,Yang Ningning,Ge Lu,Chen Nuo,Zhang Xuzi,Wang Qiuchen,Liu Xian,Zhang Xuanlong,Jiang Xiaoqiong,Geng Yibo,Zhang Chenxi,Pan Jiadong,Wang Xiangyang,Gao Weiyang,Li Zhijie,Zhang Hongyu,Ni Wenfei,Xiao Jian,Zhou Kailiang,Yang Liangliang
In the realm of large-area trauma flap transplantation, averting ischaemic necrosis emerges as a pivotal concern. Several key mechanisms, including the promotion of angiogenesis, the inhibition of oxidative stress, the suppression of cell death, and the mitigation of inflammation, are crucial for enhancing skin flap survival. Apoptotic bodies (ABs), arising from cell apoptosis, have recently emerged as significant contributors to these functions. This study engineered three-dimensional (3D)-ABs using tissue-like mouse adipose-derived stem cells (mADSCs) cultured in a 3D environment to compare their superior biological effects against 2D-ABs in bolstering skin flap survival. The findings reveal that 3D-ABs (85.74 ± 4.51) % outperform 2D-ABs (76.48 ± 5.04) % in enhancing the survival rate of ischaemic skin flaps (60.45 ± 8.95) % (all p < 0.05). Mechanistically, they stimulated angiogenesis, mitigated oxidative stress, suppressed apoptosis, and facilitated the transition of macrophages from M1 to M2 polarization (all p < 0.05). A comparative analysis of microRNA (miRNA) profiles in 3D- and 2D-ABs identified several specific miRNAs (miR-423-5p-up, miR30b-5p-down, etc.) with pertinent roles. In summary, ABs derived from mADSCs cultured in a 3D spheroid-like arrangement exhibit heightened biological activity compared to those from 2D-cultured mADSCs and are more effective in promoting ischaemic skin flap survival. These effects are attributed to their influence on specific miRNAs.
研究领域:
组织工程
·
再生医学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOLOGY
·
2024
·
IF 3.2
Nan Yang,Yue Zhang,Peiyao Ren,Li Zhao,Danna Zheng,Lanjun Fu,Juan Jin
Although LncRNA AA465934 expression is reduced in high glucose (HG)-treated podocytes, its role in HG-mediated podocyte injury and diabetic nephropathy (DN) remains unknown. Herein, we investigated the role of AA465934 in HG-mediated podocyte injury and DN using a spontaneous type II diabetic nephropathy (T2DN) model. The model was created by injecting AA465934 overexpressed adeno-associated virus (AAV) or control into mice. The levels of renal function, proteinuria, renal structural lesions, and podocyte apoptosis were then examined. Furthermore, AA465934 and autophagy levels, as well as tristetraprolin (TTP) and high mobility group box 1 (HMGB1) expression changes were detected. We also observed podocyte injury and the binding ability of TTP to E3 ligase proviral insertion in murine lymphomas 2 (PIM2), AA465934, or HMGB1. According to the results, AA465934 improved DN progression and podocyte damage in T2DN mice. In addition, AA465934 bound to TTP and inhibited its degradation by blocking TTP-PIM2 binding. Notably, TTP knock-down blocked the ameliorating effects of AA465934 and TTP bound HMGB1 mRNA, reducing its expression. Overexpression of HMGB1 inhibited the ability of AA465934 and TTP to improve podocyte injury. Furthermore, AA465934 bound TTP, inhibiting TTP-PIM2 binding, thereby suppressing TTP degradation, downregulating HMGB1, and reversing autophagy downregulation, ultimately alleviating HG-mediated podocyte injury and DN. Based on these findings, we deduced that the AA465934/TTP/HMGB1/autophagy axis could be a therapeutic avenue for managing podocyte injury and DN.
研究领域:
分子生物学
·
肾病学
·
糖尿病研究
✓ 已验证
DOI
高影响因子
Frontiers in Immunology
·
2023
·
IF 7.3
Wang Huifang,Li Yichen,Jiang Shuqi,Liu Nan,Zhou Qiuping,Li Qian,Chen Zhuo,Lin Yiyan,Chen Chunbo,Deng Yiyu
Background: Neuroinflammation is a common feature of many neurological diseases, and remains crucial for disease progression and prognosis. Activation of microglia and astrocytes can lead to neuroinflammation. However, little is known about the role of lncRNA xist and miR-122-5p in the pathogenesis of sepsis-associated neuroinflammation (SAN). This study aims to investigate the role of lncRNA xist and miR-122-5p in the pathogenesis of SAN.Methods: Levels of miR-122-5p and proinflammatory mediators were detected in the cerebrospinal fluid (CSF) of patients with intracranial infection (ICI) by ELISA and qRT-PCR. miRNA expression in the periventricular white matter (PWM) in rats was analyzed by high-throughput sequencing. Levels of lncRNA xist, miR-122-5p and proinflammatory mediators in the PWM were measured using qRT-PCR and western blot. Bioinformatics analysis was used to predict the upstream and downstream of miR-122-5p. The interaction between miR-122-5p and its target protein was validated using luciferase reporter assay. BV2 and astrocytes were used to detect the expression of lncRNA xist, miR-122-5p.Results: The level of miR-122-5p was significantly decreased in the CSF of ICI patients, while the expression of IL-1β and TNF-α were significantly upregulated. Furthermore, it was found that the expression of IL-1β and TNF-α were negatively correlated with the level of miR-122-5p. A high-throughput sequencing analysis showed that miR-122-5p expression was downregulated with 1.5-fold changes in the PWM of CLP rats compared with sham group. Bioinformatics analysis found that lncRNA xist and PKCη were the upstream and downstream target genes of miR-122-5p, respectively. The identified lncRNA xist and PKCη were significantly increased in the PWM of CLP rats. Overexpression of miR-122-5p or knockdown of lncRNA xist could significantly downregulate the level of PKCη and proinflammatory mediators from activated microglia and astrocytes. Meanwhile, in vitro investigation showed that silencing lncRNA xist or PKCη or enhancing the expression of miR-122-5p could obviously inhibit the release of proinflammatory mediators in activated BV2 cells and astrocytes.Conclusion: LncRNA xist could regulate microglia and astrocytes activation in the PWM of CLP rats via miR-122-5p/PKCη axis, further mediating sepsis associated neuroinflammation.
研究领域:
神经科学
·
炎症学
·
分子生物学
·
微生物学
✓ 已验证
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Jiao Yang,Yanzhou Li,Longhua Guo,Bin Qiu,Zhenyu Lin
Conventional photosensitive materials such as TiO2 suffer from restricted absorption in the ultraviolet region, fast recombination of photogenerated electron–hole pairs, and a lack of functional groups for biocoupling, which hinder their application in photoelectrochemical (PEC) biosensing. Herein, a new coordination polymer (CP) based on Cu(I), chloridion, and 4-mercaptobenzoic acid (MBA) has been designed and synthesized (called CuClx(MBA)y). The prepared p-type CuClx(MBA)y exhibits visible-light absorption due to its narrow optical band gap (2.59 eV), and its proper band edge position enables it to form a p–n junction with TiO2. Through layer-by-layer assembling, the photocurrent intensity of the CuClx(MBA)y/TiO2/FTO composite photoelectrode was 3.7-fold higher than that of a TiO2/FTO electrode and 35-fold higher than a CuClx(MBA)y/FTO electrode. The potential enhancement mechanism was discussed, which lies in the contributions of CuClx(MBA)y in enhancing absorption in the visible-light region and boosting the separation of electron–hole pairs of TiO2 by the p–n junction. Furthermore, CuClx(MBA)y nanosheets can realize bioconjugation directly, thanks to its abundant carboxyl groups. The CuClx(MBA)y/TiO2/FTO composite photoelectrodes were applied to develop a sensitive PEC biosensor for microRNA-21 (model target). By subtly exploiting the energy transfer between CuClx(MBA)y and Au nanoparticles (AuNPs), AuNPs served as effective quenchers. In the presence of the target, AuNP-labeled sDNA1 connected to the electrode surface, and thus, a decreased photocurrent was obtained. The proposed biosensor has a low detection limit of 0.29 fM (S/N = 3), good selectivity, and reproducibility. The proposed system was applied to monitor microRNA in cancer cells with satisfying results.
研究领域:
生物化学
·
分析化学
·
纳米技术
·
分子生物学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Hua Jiang,Xiaotian Zhang,Shengyu Feng,Wei Feng
Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by motor dysfunction and dopaminergic neuron loss. Although its genetic and molecular underpinnings have been increasingly studied, the pathways driving PD progression remain unclear. The integrated stress response (ISR), a conserved mechanism activated by cellular stress, has been linked to several neurological diseases, but its role in PD and the key ISR-related genes involved are still poorly understood.Materials and Methods We used publicly available transcriptomic data from GEO, including single-cell RNA sequencing and spatial transcriptomics, to identify ISR-related genes involved in PD progression. ISR scores were compared across brain cell types, and differentially expressed genes in microglia were further screened using Lasso regression and random forest algorithms. Enrichment analyses (GSEA and GSVA) revealed their involvement in immune-related pathways. CIBERSORT was applied to assess immune cell infiltration, while spatial transcriptomics mapped the regional expression of key genes. Finally, DDIT4 expression was validated in PD cell and mouse models.Results We identified four key ISR-related genes (DDIT4, GNA13, HSPA1B, and SLC7A5) that were differentially expressed in PD microglia. Functional enrichment analysis revealed that these genes were predominantly involved in immune-related signaling pathways, including JAK-STAT, NF-κB, and Notch, suggesting their potential role in regulating neuroinflammation. Spatial transcriptomics revealed distinct regional expression patterns of these ISR-related genes across brain tissues. In vitro and in vivo experiments confirmed the upregulation of DDIT4 in PD models, and its silencing alleviated neurotoxicity and reduced α-synuclein aggregation, highlighting its potential role in PD pathogenesis.Conclusion This study provides new insights into the molecular mechanisms of PD and highlights DDIT4 as a promising therapeutic target. Its regulatory role in immune signaling and cellular stress pathways may offer novel avenues for clinical intervention and personalized treatment strategies in PD.
研究领域:
神经病学
·
基因组学
·
免疫学
·
生物信息学
·
神经退行性疾病
·
转录组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Fengling Feng,Haibin Hao,Jin Zhao,Yanjun Li,Ying Zhang,Ruiting Li,Ziyu Wen,Chunxiu Wu,Minchao Li,Pingchao Li,Ling Chen,Ruikang Tang,Xiaoyu Wang,Caijun Sun
Adenovirus (Ad) has been extensively developed as a gene delivery vector, but the potential side effect caused by systematic immunization remains one major obstacle for its clinical application. Needle-free mucosal immunization with Ad-based vaccine shows advantages but still faces poor mucosal responses. We herein report that the chemical engineering of single live viral-based vaccine effectively modulated the location and pattern of the subsequently elicited immunity. Through precisely assembly of functional materials onto single live Ad particle, the modified virus entered host cell in a phagocytosis-dependent manner, which is completely distinct from the receptor-mediated entry of native Ad. RNA-Seq data further demonstrated that the modified Ad-induced innate immunity was sharply reshaped via phagocytosis-related pathway, therefore promoting the activation and mature of antigen presentation cells (APC). Moreover, the functional shell enabled the modified Ad-based vector with enhanced muco-adhesion to nasal tissues in mice, and then prolonged resident time onto mucosal surface, leading to the robust mucosal IgA production and T cell immunity at local and even remote mucosal-associated lymphoid tissues. This study demonstrated that vaccine-induced immunity can be well modulated by chemistry engineering, and this method provides the rational design for needle-free mucosa-targeting vaccine against a variety of emerging infectious diseases.
研究领域:
病毒学
·
免疫学
·
生物医学工程
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 19
·11257-11262
·
IF 3.119
Xitong Huang,Zhiming Xu,Ji-Hua Liu,Bo-Yang Yu,Jiangwei Tian
MicroRNA-21 (miRNA-21) is a significant biomarker which is closely related to some kinds of diseases, such as cancer, cardiovascular disease and kidney disease. Therefore, the detection of miRNA-21 is of great importance and can provide essential information for disease diagnosis. In this study, we report a facile, sensitive assay for miRNA-21 detection using personal glucose meters (PGM). Biotinylated DNA strand linked invertase (Inv) is conjugated on the surface of streptavidin-coated magnetic beads (MBs) to form a MBs–DNA–Inv complex. Target miRNA-21 in the detection system is captured by the MBs–DNA–Inv probe through DNA/RNA hybridization. The duplex-specific nuclease (DSN) enzyme specifically cleaves the DNA to recycle the target miRNA and release invertase, thereby triggering the dual signal amplification and ensuring high sensitivity. Besides, we establish a linear relationship between PGM and different concentrations of miRNA-21 in the range of 10 to 200 pM. The limit of detection is 1.8 pM, which is more sensitive than some of the previous reports. In addition, the biosensor exhibits excellent sequence selectivity and single-base mutation can be discriminated. Moreover, the expression of miRNA-21 is confirmed in urine from mice by our method, which is in good accordance with the qRT-PCR result. Therefore, a dependable, low-cost strategy for the detection of miRNA has been established and it meets the latest analytical demands for miRNA determination that is suitable for the public.
研究领域:
生物传感器
·
分子生物学
·
分析化学
·
疾病诊断
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）