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
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基因组学
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免疫学
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生物信息学
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神经退行性疾病
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转录组学
✓ 已验证
产品关联
DOI
PubMed
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
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分析化学
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纳米技术
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分子生物学
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癌症研究
✓ 已验证
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2020
·
IF 3.594
Yihui Ma,Nianzu Liu,Zhenying Xu,Jingjing Wang,Xiliang Luo
The rapid, selective and ultrasensitive assaying of biomarkers remains a challenge relevant to biosensor/diagnostic applications. Herein, a promising electrochemical biosensor based on three-dimensional (3D) nanoporous conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) decorated with gold nanoparticles (AuNPs) was developed, in which methylene blue (MB) was employed as redox indicator for microRNA24 (miRNA24) detection. The unique porous construction was fabricated by a simple hard-template method and cyclic voltammetry (CV) electrochemical technique. AuNPs were electrodeposited onto the porous PEDOT surface to increase the interface conductivity and provide more active sites to load identification elements. The obtained porous biosensor based on conducting polymer PEDOT and AuNPs exhibited significantly enlarged specific surface area (about 2.4 times) and enhanced sensitivity (about 2.1 times), compared to the biosensor based on planar PEDOT. The developed porous biosensor achieved a miRNA24 quantification range from 1 fM to 10 nM with satisfying stability, high selectivity, and a low limit of detection (0.38 fM). The construction of biosensors based on porous conducting polymers decorated with AuNPs offers an effective strategy to increase the electroactive surface area of the sensing interfaces, so as to effectively enhance the sensitivity.
研究领域:
生物传感器
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电化学
·
纳米技术
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分析化学
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分子诊断
✓ 已验证
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Fenghe Duan,Chuanpan Guo,Mengyao Hu,Yingpan Song,Minghua Wang,Linghao He,Zhihong Zhang,Riccardo Pettinari,Liming Zhou
A promising nanocarrier of the complementary DNA (cDNA) toward miRNA-155 was synthesized on the basis of the nanohybrid type of Ti 3 C 2 T x MXene nanosheets decorated using iron phthalocyanine quantum dots (FePc QDs) (denoted as Ti 3 C 2 T x @FePcQDs) to construct a novel ultrasensitive impedimetric aptasensing system for microRNA-155 (miRNA-155). Owing to π–π* stacking interaction between Ti 3 C 2 T x nanosheets and FePc QDs, the homogeneous nanostructure of the Ti 3 C 2 T x @FePcQD nanohybrid that comprises mixed-valence states (Ti 2+ /Ti 3+ and Fe 2+ /Fe 3+ ), multicomponent (Ti-O and Ti-C), and various N-related groups was achieved. The constructed Ti 3 C 2 T x @FePcQDs-based aptasensor displayed an ultrahigh sensitivity for detecting miRNA-155 with a low detection limit of 4.3 aM (S/N = 3) within the miRNA-155 concentration ranging from 0.01 fM to 10 pM. Compared with the individual component-based aptasensors and other reported miRNA-155 aptasensors, the proposed impedimetric aptasensing system exhibited substantial merits of a feasible preparation process, non-use of labels or electrochemical indicators, fast response time, and comprehensive sensing performances for detecting miRNA-155. This strategy for determining miRNAs can extensively be applied as the platform for anchoring other kinds of aptamers in detecting diverse targets, thus indicating its great potential application for the early diagnosis of cancer biomarkers.
研究领域:
纳米技术
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生物传感器
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分析化学
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分子生物学
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癌症研究
✓ 已验证
DOI
高影响因子
iScience
·
2022
·
IF 6.107
Fanyang Lv,Yuhua Zhan,Wei Lu,Xiubin Ke,Yahui Shao,Yiyuan Ma,Juan Zheng,Zhimin Yang,Shanshan Jiang,Liguo Shang,Yao Ma,Lei Cheng,Claudine Elmerich,Yongliang Yan,Min Lin
Summary Bacteria of the genus Pseudomonas consume preferred carbon substrates in nearly reverse order to that of enterobacteria, and this process is controlled by RNA-binding translational repressors and regulatory ncRNA antagonists. However, their roles in microbe-plant interactions and the underlying mechanisms remain uncertain. Here we show that root-associated diazotrophic Pseudomonas stutzeri A1501 preferentially catabolizes succinate, followed by the less favorable substrate citrate, and ultimately glucose. Furthermore, the Hfq/Crc/CrcZY regulatory system orchestrates this preference and contributes to optimal nitrogenase activity and efficient root colonization. Hfq has a central role in this regulatory network through different mechanisms of action, including repressing the translation of substrate-specific catabolic genes, activating the nitrogenase gene nifH posttranscriptionally, and exerting a positive effect on the transcription of an exopolysaccharide gene cluster. Our results illustrate an Hfq-mediated mechanism linking carbon metabolism to nitrogen fixation and root colonization, which may confer rhizobacteria competitive advantages in rhizosphere environments.
研究领域:
微生物学
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植物科学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Science Advances
·
2023
·Vol. 9
·期 6
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IF 13.6
Lei Xiang,Jing Liang,Zhen Wang,Feng Lin,Yaping Zhuang,Qimanguli Saiding,Fei Wang,Lianfu Deng,Wenguo Cui
Mechanical activation of fibroblasts, caused by friction and transforming growth factor–β1 recognition, is one of the main causes of tissue adhesions. In this study, we developed a lubricated gene-hydrogel patch, which provides both a motion lubrication microenvironment and gene therapy. The patch’s outer layer is composed of polyethylene glycol polyester hydrogel. The hydrogel forms hydrogen bonds with water molecules to create the motion lubrication layer, and it also serves as a gene delivery library for long-term gene silencing. Under the motion lubricated microenvironment, extracellular signal–regulated kinase–small interfering RNA can silence fibroblasts and enhance the blocking effect against fibroblast activation. In vitro, the proposed patch effectively inhibits fibroblast activation and reduces the coefficient of friction. In vivo, this patch reduces the expression of vimentin and α–smooth muscle actin in fibroblasts. Therefore, the lubricated gene-hydrogel patch can inhibit the mechanical activation of fibroblasts to promote tendon healing.
研究领域:
生物医学工程
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组织工程
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基因治疗
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骨科
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Liu Bin,Li Faping,Wang Yuxiong,Gao Xin,Li Yunkuo,Wang Yishu,Zhou Honglan
Background: Kidney injuries often carry a grim prognosis, marked by fibrosis development, renal function loss, and macrophage involvement. Despite extensive research on macrophage polarization and its effects on other cells, like fibroblasts, limited attention has been paid to the influence of non-immune cells on macrophages. This study aims to address this gap by shedding light on the intricate dynamics and diversity of macrophages during renal injury and repair.Methods: During the initial research phase, the complexity of intercellular communication in the context of kidney injury was revealed using a publicly available single-cell RNA sequencing library of the unilateral ureteral obstruction (UUO) model. Subsequently, we confirmed our findings using an independent dataset from a renal ischemia-reperfusion injury (IRI) model. We treated two different types of endothelial cells with TGF-β and co-cultured their supernatants with macrophages, establishing an endothelial cell and macrophage co-culture system. We also established a UUO and an IRI mouse model. Western blot analysis, flow cytometry, immunohistochemistry and immunofluorescence staining were used to validate our results at multiple levels.Results: Our analysis revealed significant changes in the heterogeneity of macrophage subsets during both injury processes. Amyloid β precursor protein (APP)-CD74 axis mediated endothelial-macrophage intercellular communication plays a dominant role. In the in vitro co-culture system, TGF-β triggers endothelial APP expression, which subsequently enhances CD74 expression in macrophages. Flow cytometry corroborated these findings. Additionally, APP and CD74 expression were significantly increased in the UUO and IRI mouse models. Immunofluorescence techniques demonstrated the co-localization of F4/80 and CD74 in vivo.Conclusion: Our study unravels a compelling molecular mechanism, elucidating how endothelium-mediated regulation shapes macrophage function during renal repair. The identified APP-CD74 signaling axis emerges as a promising target for optimizing renal recovery post-injury and preventing the progression of chronic kidney disease.
研究领域:
肾病学
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免疫学
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分子生物学
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细胞生物学
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病理生理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL MANAGEMENT
·
2024
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IF 8
Guangxia Xu,Xiaoyu Long,Junjie Zhai,Yunhao Liu,Chaowei Wang,Jinbu Li,Xing Wang
Widespread use of the pyrethroid insecticide beta-cypermethrin (beta-CYP) has led to adverse effects on nontarget populations within agroecosystems. Despite the efficacy of beta-CYP in pest control, its toxicological and defense mechanisms remain incompletely understood. In the present study, we explored the toxicological effects, antioxidant mechanisms and immune response against beta-CYP using Drosophila melanogaster , a well-established model organism for the study of insect biology, to represent the broader class of nontarget organisms. We exposed Drosophila larvae to 0.667 μg/mL beta-CYP and revealed that delayed development and caused intestinal epithelial damage in larvae. To gain insights into the molecular underpinnings of these effects, RNA sequencing analysis and quantitative polymerase chain reaction validation were performed. These analyses revealed that the messenger RNA levels of glutathione S-transferase were increased, third instar larvae exhibited an increase in reactive oxygen species content and a corresponding increase in antioxidant enzyme activity in response to beta-CYP exposure, indicating an upregulated response to oxidative stress. Beta-CYP also activated Hippo pathway to resist apoptosis and promote cell proliferation. Moreover, beta-CYP induced melanization and Toll immune pathways involved in immune response in Drosophila larvae, specifically the Toll pathway gene Drs . This activation suggests that Drosophila increases antioxidant defenses and promotes mitosis in damaged tissues as compensatory mechanisms to mitigate the cytotoxic effects of beta-CYP. These findings provide new insight into the mechanisms of beta-CYP–induced toxicity and the defense mechanisms in insects; they may also inform strategies for the sustainable use of insecticides and the development of mitigation measures to protect nontarget species in agroecosystems.
研究领域:
毒理学
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昆虫生物学
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分子生物学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Bioresources and Bioprocessing
·
2022
·Vol. 9
·期 1
·1-12
·
IF 4.983
Ye Jing,Li Yunjie,Bai Yuqing,Zhang Ting,Jiang Wei,Shi Ting,Wu Zijian,Zhang Yi-Heng P. Job
To mimic the Escherichia coli T7 protein expression system, we developed a facile T7 promoter-based protein expression system in an industrial microorganism Bacillus subtilis. This system has two parts: a new B. subtilis strain SCK22 and a plasmid pHT7. To construct strain SCK22, the T7 RNA polymerase gene was inserted into the chromosome, and several genes, such as two major protease genes, a spore generation-related gene, and a fermentation foam generation-related gene, were knocked out to facilitate good expression in high-density cell fermentation. The gene of a target protein can be subcloned into plasmid pHT7, where the gene of the target protein was under tight control of the T7 promoter with a ribosome binding site (RBS) sequence of B. subtilis (i.e., AAGGAGG). A few recombinant proteins (i.e., green fluorescent protein, α-glucan phosphorylase, inositol monophosphatase, phosphoglucomutase, and 4-α-glucanotransferase) were expressed with approximately 25–40% expression levels relative to the cellular total proteins estimated by SDS-PAGE by using B. subtilis SCK22/pHT7-derived plasmid. A fed-batch high-cell density fermentation was conducted in a 5-L fermenter, producing up to 4.78 g/L inositol monophosphatase. This expression system has a few advantageous features, such as, wide applicability for recombinant proteins, high protein expression level, easy genetic operation, high transformation efficiency, good genetic stability, and suitability for high-cell density fermentation.
研究领域:
微生物学
·
生物技术
·
分子生物学
·
基因工程
✓ 已验证
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Kun Xiao,Pengfei Liu,Peng Yan,Yanxin Liu,Licheng Song,Yuhong Liu,Lixin Xie
Lung ischemia/reperfusion (I/R) injury (LIRI) is a common complication after lung transplantation, embolism, and trauma. N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of I/R injury. However, there are no or few reports of m6A-related regulators in LIRI till now. In this text, dysregulated genes in lung tissues of LIRI rats versus the sham group were identified by RNA sequencing (RNA-seq). RNA-seq outcomes revealed that only YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) were differentially expressed in the LIRI versus sham group among 20 m6A-related regulators. Next, the functions and molecular mechanisms of YTHDF3 and IGF2BP2 in LIRI were investigated in a hypoxia/reoxygenation-induced BEAS-2B cell injury model in vitro. Results showed that YTHDF3 or IGF2BP2 knockdown attenuated hypoxia/reoxygenation-mediated inhibitory effects on cell survival and cell cycle progression and inhibited hypoxia/reoxygenation-induced cell apoptosis and pro-inflammatory cytokine secretion in BEAS-2B cells. Genes that could be directly regulated by YTHDF3 or IGF2BP2 were identified based on prior experimental data and bioinformatics analysis. Moreover, multiple potential downstream pathways of YTHDF3 and IGF2BP2 were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis of the above-mentioned genes. Among these potential pathways, we demonstrated that YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-κB pathways in BEAS-2B cells. In conclusion, YTHDF3 or IGF2BP2 knockdown weakened hypoxia/reoxygenation-induced human lung bronchial epithelial cell injury by inactivating p38, AKT, ERK1/2, and NF-κB pathways.
研究领域:
分子生物学
·
细胞生物学
·
免疫学
·
移植医学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Fang Hu,Wancun Zhang,Jiaqi Zhang,Qi Zhang,Tao Sheng,Yueqing Gu
In this study, a simple, economic, and label-free electrochemical biosensor was developed for highly sensitive and selective miR-21 detection based on Fe(CN) 6 3− /Fe(CN) 6 4− electrochemical signal, which relies on DNA structures conjugating with carboxyl multi-wall carbon nanotubes (MWCNTs-COOH)-modified glassy carbon electrode (GCE). High sensitivity and specificity of the biosensor were achieved by taking advantage of the target-recycled non-enzymatic amplification strategy (TRNEAS), which relies on sequence-specific hairpin strand displacement and does not require the addition of environment-susceptible enzymes. Besides, the SP-DNA strictly binds to the cMWCNTs/GCE via amide bonds, which ensure good electrochemical results and excellent stability for target miRNA detection. The developed miR-21 electrochemical biosensor exhibited a broad linear dynamic range of 0.1 fmol to 5 pmol and a detection limit of 56.7 amol for miR-21 detection in vitro . The relative miR-21 expression levels were particularly detected by our developed miR-21 biosensor and were highly consistent with the stem-loop RT-PCR results. In summary, our developed electrochemical biosensor exhibits great potential for further application in biomedical research and early clinical diagnosis.
研究领域:
生物传感器
·
电化学
·
纳米技术
·
分子生物学
·
临床诊断
✓ 已验证
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Wei Xu,Sijia Fang,Yong Wang,Xiaoqing Chi,Xiaodan Ma,Tao Zhang,Songhua Hu
The present study was to investigate the molecular mechanism underlying lymphocyte activation by total polysaccharides from Atractylodis macrocephalae (RAMPtp). The results showed that RAMPtp significantly promoted the secretions of cytokines (IFN-γ, IL-1α, IL-21, IFN-α, CCL4, CXCL9 and CXCL10), increased the proportions of CD4 + and CD8 + subpopulations, and enhanced the expressions of c-JUN, NFAT4, STAT1 and STAT3. microRNA sequencing identified 67 differentially expressed miRNAs (DEMs) in RAMPtp-stimulated SMLN lymphocytes, including 55 up-regulated and 12 down-regulated. GO and KEGG enrichment analyses of the predicted DEMs-targeted genes indicated that they were associated with immune system pathways, including PI3K-Akt, MAPKs, Jak-STAT and Calcium signaling pathways, which were confirmed by western blot and pathway inhibition assays. RAMPtp was further observed to favor immunostimulatory effect on both T and B lymphocytes via binding to TCR and membrane Ig individually. These findings might explain the immunomodulatory mechanism of RAMPtp in ameliorating the bovine intramammary infection.
研究领域:
免疫学
·
分子生物学
·
兽医学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）