Small
·
2025
·
IF 12.1
Ruotian Zhang,Yanzhen Song,Jiawei Yao,Hanfeng Qin,Yicheng Ye,Junbin Gao,Cheng Zhang,Dayong Han,Ming Gao,Hao Chen,Xin Chen,Shiguang Zhao,Kun Liu,Yingfeng Tu,Zhili Xu
Postoperative recurrence of glioblastoma (GBM) is a key contributing factor to the unfavorable prognosis of patients. Chemotherapy has been extensively employed as a postoperative treatment for GBM; however, the produced drug resistance significantly undermines the chemotherapeutic efficacy. Herein, a multifunctional system based on magnesium micromotor (Mg-Motor-DOX) is designed and fabricated that can generate hydrogen gas in situ and actively deliver the chemotherapeutic drug doxorubicin (DOX). Utilizing a temperature-sensitive hydrogel, Mg-Motor-DOX is administrated in situ to the residual cavity of the tumor after subtotal GBM resection. The produced H 2 by the Mg-water reaction not only propels the motion of motors but also functions as an antioxidant to effectively alleviate the neuroinflammation caused by GBM resection. The H 2 bubbles create a pronounced vortex flow in situ, greatly enhancing the DOX penetration and the sensitivity of GBM cells to DOX. Therefore, synergistic hydrogen-chemotherapy significantly inhibits the recurrence of the in situ GBM model. RNA-Seq technology further elucidates the role of the strategy in modulating the tumor immune microenvironment via converting cold tumors into hot tumors, thereby establishing a theoretical foundation for the clinical implementation of synergistic hydrogen-chemotherapy.
研究领域:
生物医学工程
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肿瘤学
·
分子生物学
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DOI
PubMed
高影响因子
Journal of Cancer
·
2021
·
IF 4.207
Yong-Zhi Lun,Jie Sun,Ben Liu,Wen Dong,Ling-Hong Pan,Jian Lin,Jing-Xia Zhang
Objective: As targeted drugs, exogenous serpins could be introduced to patients to restore body balance. This study aimed to observe further the inhibitory effects of recombinant Hespintor (a Kazal-type serpin) combined with Sorafenib on transplanted human hepatoma tumors in nude mice specimens and to explore the possible transcriptional regulation by Hespintor. Methods: A model of human hepatoma tumors transplanted in nude mice was established, and the medication was administrated to observe the growth of the tumors. Four weeks after the drug administration, the tumors were removed to evaluate the inhibition effects of Hespintor on in-situ tumor growth and liver metastasis. The expression levels of MMP2, MMP9, Bax, Bcl-2, and caspase-3 in the tumor organizations were detected with Western blot. The target genes of the Hespintor were screened based on tissue RNA-Seq, and the regulatory network was constructed. Results: It was found that the recombinant Hespintor displayed a significant antitumor effect on the subcutaneous growth of MHCC97-H cells. Moreover, the therapeutic effects of the combination therapy were significantly better than those of single therapy. 10 target genes with significantly different expression by Hespintoron tumor tissue were identified. Finally, a visual regulatory networkwas constructed for target mRNA-pathway. Conclusions: The antitumor effect of Hespintor combined with Sorafenib in treating the subcutaneously implanted hepatocellular carcinoma tumors in nude mice was significant. The possible transcriptional regulation by Hespintor involved multiple signaling pathways, and it was not just the antitumor effect of uPA via its extracellular inhibitions.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2024
·
IF 3.7
Xilin Huang,Xuli Gao,Junbao Huang,Yani Luo,Wei Tao,Mingyu Guo,Yongyuan Liu,Jing Wu,Yu Chen,Yan Liu
A recombinant strain (BS168-Δ bdhA ) that increased co-production of MK-7 and NK was constructed by knocking out the 2,3-butanediol dehydrogenase gene ( bdhA ) of Bacillus subtilis 168 to reduce the carbon spillover. The results showed that the 2,3- butanediol content in the recombinant strain was reduced by 64% to 2.76 g/L. The recombinant strain had an MK-7 production of 30.6 mg/L and an NK activity of 6.5 FU/mL. RNA-Seq analysis showed that: bdhA knockdown blocked the carbon flux of 2,3-butanediol and promoted glycerol uptake, and the carbon flux flowed more to the MK-7 and NK synthesis pathways. The negative regulator of NK, codY , was down-regulated by 2.19-fold. secA , which is responsible for the energy supply of transmembrane proteins, was down-regulated by 0.37-fold, the Tat secretion pathway was up-regulated by 2.8-fold and 0.5-fold for tatAD and tatC , respectively. This study revealed the mechanism of co-production of MK-7 and NK in recombinant strains for the first time and revealed potential molecular targets to promote the co-production of MK-7 and NK, which will provide a new strategy for metabolic engineering to increase the production of MK-7 and NK.
研究领域:
微生物学
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分子生物学
·
代谢工程
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产品关联
DOI
高影响因子
Frontiers in Nutrition
·
2025
·
IF 5.1
Yanchu Li,Yuying Yang,Junyao Li,Rui Guo,Zhiqiang Niu,Weicheng Hu,Shucheng Liu,Shuai Wei
Introduction: Tropomyosin (TM) is the primary allergen in Litopenaeus vannamei, which usually causes allergic reactions that may be health or even life-threatening for consumers. Therefore, exploring the sensitization mechanism is of great significance for the prevention and treatment of tropomyosin allergy.Methods and results: In this study, TM sensitization models were using Balb/c mice, Caco-2 cells and RBL-2H3 cells to reveal the sensitization effect. The results of ELISA and RT-qPCR showed that TM can exacerbate the allergic reaction by reducing the mRNA expression of tight junction (TJ) proteins (such as ZO-1, claudin-3, Occludin) in the jejunum, destroying the intestinal barrier function, increasing the permeability, and promoting the release of inflammatory factors (such as IL-8, TNF-α) and histamine. The pathological results of intestinal tissue sections showed that TM also caused an increase in intestinal inflammatory infiltration in mice. RNA-seq analysis revealed that key genes (CCL2, HSP1A, GM-CSF, etc.) and PI3K/Akt signaling pathway were involved in the sensitization process. In vitro experiments were conducted to construct TM sensitized Caco-2 and RBL-2H3 cell models at a dose of 100 mg/mL. The results indicated that TM upregulated the expression of phosphorylated PI3K/ Akt and NFκB pathways in Caco-2 cells, further damaged the TJ structure of intestinal epithelial cells and promoted the release of inflammatory factors. The RBL-2H3 cell degranulation assay indicated that TM could directly stimulate the release of TNF-α from mast cells.Conclusion: The above experimental results indicated that PI3K/Akt signaling pathways play a crucial role in the induction of TM allergic responses, which provides a theoretical basis for the occurrence, development and prevention of TM allergy.
研究领域:
免疫学
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分子生物学
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药理学
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生物医学
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产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2020
·
IF 2.751
Benshui Shu,Haikuo Yu,Yuning Li,Hongxin Zhong,Xiangli Li,Liang Cao,Jintian Lin
The fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) is a polyphagous pest with 353 plant species as its hosts, including maize, sorghum, cotton, and rice. Azadirachtin is one of the most effective botanical insecticides . The effect of azadirachtin against S. frugiperda remains to be determined. Here we report strong growth inhibition of azadirachtin on S. frugiperda larvae under either 1.0 or 5.0 μg/g azadirachtin. To explore the relevant mechanisms, the larvae fed with normal artificial diet and with 1.0 μg/g azadirachtin exposure for 3 days were collected as samples for RNA-Seq. RNA-Seq on S. frugiperda larvae under different treatments identified a total of 24,153 unigenes , including 3494 novel genes, were identified. Among them, 1282 genes were affected by 1.0 μg/g azadirachtin exposure, with 672 up-regulated and 610 down-regulated. The impacted genes include 61 coding for detoxification enzymes (31 P450s , 7 GSTs , 11 CarEs , 7 UGTs and 5 ABC transporters), 31 for cuticle proteins, and several proteins involved in insect chitin and hormone biosynthesis . Our results indicated that azadirachtin could regulate the growth of S. frugiperda by affecting insect chitin and hormone biosynthesis pathway. The enhanced expression of detoxification enzymes might be related to detoxifying azadirachtin. These findings provided a foundation for further delineating the molecular mechanism of growth regulation induced by azadirachtin in S. frugiperda larvae.
研究领域:
昆虫学
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分子生物学
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农药科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Teng Wang,Mengyao Hu,Huilin Chen,Yan Chen,Chunyu Niu,Yin Chen
This study utilized GC–MS and NMR to characterize the detailed chain structure information of polysaccharide (HM0–1) from the Agelas aff. Nemoechinata sponge, and then explored its anti-liver cancer in vitro. Results showed that the HM0–1 was a homogeneous amino-polysaccharide with a molecular weight of 929 kDa, composed of mannose (Man), N-Acetyl-glucosamine (GlcNAc), N-Acetyl-galactosamine (GalNAc), galactose (Gal) and fucose (Fuc). The main chain of HM0–1 was composed of α-(1 → 2)-linked Man and α-(1 → 6)-linked GlcNAc, and the side chains were α-Gal p (1→, α-Fuc p -(1 → 3)-α-Gal p -(1→, α-Man p -(1→) and a branch composed of GalNAc and Gal, which was connected to the main chain through the 3- O position of →2)-β-Man p -(1→and→6)-β-Man p -(1→. Additionally, HM0–1 exhibited anti-liver cancer effects by inhibiting cell proliferation, migration and invasion, and inducing cell apoptosis. We further investigated the potential mechanism of HM0–1-induced apoptosis by RNA-seq, which revealed 3679 significantly altered DEGs. GO enrichment analysis of the DEGs revealed significant enrichment of 2444 GO terms throughout the differentiation process ( P < 0.05). KEGG analysis showed that the DEGs were successfully annotated as members of 347 pathways, with 42 significantly enriched KEGG pathways. In conclusion, these studies can provide valuable insights into the potential development and utilization of sponge polysaccharides as marine natural bio-active compounds.
研究领域:
海洋生物学
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分子生物学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2019
·Vol. 9
·期 11
·695
·
IF 4.694
Dong-Sheng Wang,Xin-Jun Yu,Xiao-Yu Zhu,Zhao Wang,Hui-Juan Li,Zhi-Peng Wang
In the current study, corn steep liquor (CSL) is evaluated as an ideal raw agro-material for efficient lipid and docosahexaenoic acid DHA production byAurantiochytriumsp. Low CSL level in medium (nitrogen deficiency) stimulated the biosynthesis of lipids and DHA while inhibiting cellular growth. The transcriptomic profiles of theAurantiochytriumsp. cells are analyzed and compared when cultured under high (H group), normal (N group), and low (L group) levels of CSL in the medium. The discriminated transcriptomic profiles from the three groups indicates that changes in CSL level in medium result in a global change in transcriptome ofAurantiochytriumsp. The overall de novo assembly of cDNA sequence data generated 61,163 unigenes, and 18,129 of them were annotated in at least one database. A total of 5105 differently expressed (DE) genes were found in the N group versus the H group, with 2218 downregulated and 2887 upregulated. A total of 3625 DE genes were found in the N group versus the L group, with 1904 downregulated and 1721 upregulated. The analysis and categorization of the DE genes indicates that the regulation mechanism of CSL involved in the perception and transduction of the limited nitrogen signal, the interactions between the transcription factors (TFs) and multiple downstream genes, and the variations in downstream genes and metabolites, in sequence, are illuminated for the first time in the current study.Keywords:Aurantiochytriumsp.;nitrogen-deficiency;RNA-seq;corn steep liquor (CSL);signal transduction;DHA
研究领域:
生物技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Physiology
·
2025
·
IF 3.4
Senyue Liu,Qiang Li,Yongqiang Deng,Zhongwei Wang,Yang Feng,Han Zhao,Zhongmeng Zhao,Lu Zhang,Yuanliang Duan,Zhipeng Huang,Jian Zhou,Chengyan Mou
Understanding how distinct brain regions of Leiocassis longirostris molecularly adapt to heat stress is vital for improving aquaculture sustainability and guiding conservation strategies in a warming climate. To elucidate the region-specific molecular mechanisms underlying heat stress responses in the brain of L. longirostris , we exposed L. longirostris to acute heat stress (32°C) for 24 h and performed RNA-seq and WGCNA on five brain regions (OB: olfactory bulb, FB: pituitary, hypothalamus, forebrain, MB: mesencephalon, CB: cerebellum, and SC: spinal cord). The results showed that, after heat stress, the FB region significantly activated the ER stress pathway, and the abnormal proteins were synergically cleared by HSP-mediated UPR (such as Hsp70, Hsp90, IRE1α, Perk, ATF6) and UPS-mediated ERAD (such as UBE2, UBE3, TRIM63). Meanwhile, the SC region showed marked downregulation of lipid metabolism and PPAR signaling pathway, suggesting energy conservation as a compensatory strategy. WGCNA further highlighted the FB as the hub for ER stress and the SC for metabolic suppression. In conclusion, our study suggests that distinct brain regions of L. longirostris adopt different strategies under heat stress, in which the FB region mediates protein quality control and the SC region drives metabolic inhibition. These findings highlight the adaptation strategies of the L. longirostris brain to heat stress and provides a potential target for improving its survival under global warming.
研究领域:
分子生物学
·
神经科学
·
水产养殖学
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产品关联
DOI
PubMed
高影响因子
PeerJ
·
2023
·
IF 2.7
Wanwei Hou,Xiaojuan Zhang,Yuling Liu,Yujiao Liu,Bai li Feng
Background Faba bean ( Vicia faba L) is one of the most important legumes in the world. However, there is relatively little genomic information available for this species owing to its large genome. The lack of data impedes the discovery of molecular markers and subsequent genetic research in faba bean. The objective of this study was to analyze the faba bean transcriptome, and to develop simple sequence repeat (SSR) markers to determine the genetic diversity of 226 faba bean varieties derived from different regions in China. Methods Faba bean varieties with different phenotype were used in transcriptome analysis. The functions of the unigenes were analyzed using various database. SSR markers were developed and the polymorphic markers were selected to conduct genetic diversity analysis. Results A total of 92.43 Gb of sequencing data was obtained in this study, and 133,487 unigene sequences with a total length of 178,152,541 bp were assembled. A total of 5,200 SSR markers were developed on the basis of RNA-Seq analysis. Then, 200 SSR markers were used to evaluate polymorphisms. In total, 103 (51.5%) SSR markers showed significant and repeatable bands between different faba bean varieties. Clustering analysis revealed that 226 faba bean materials were divided into five groups. Genetic diversity analysis revealed that the relationship between different faba beans in China was related, especially in the same region. These results provided a valuable data resource for annotating genes to different categories and developing SSR markers.
研究领域:
植物学
·
遗传学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
·
2023
·Vol. 22
·期 4
·905-917
·
IF 3.1
Wen Ying,Zeng Liyun,Chen Qitong,Li Yitong,Fu Mengdie,Wang Zixin,Liu Hong,Li Xiejia,Huang Peng,Wu Wei,Zou Qiongyan,Yi Wenjun
Background The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. Methods Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. Results In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM–receptor interaction, focal adhesion and protein digestion and absorption. Protein–protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. Conclusions The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT. Graphical abstract
研究领域:
转录组学
·
光动力疗法
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Huang Zihua,Xie Luoyijun,Zhang Jifan,Li Qiyan,Liu Yulin,Fu Xuemei,Yuan Miaomiao,Li Qingjiao
Mesoporous polydopamine nanoparticles (MPDA NPs) are promising nanomaterials that have the prospect of clinical application for multi-strategy antitumor therapy, while the biosecurity of MPDA NPs remains indistinct. Here, transcriptome sequencing (RNA-Seq) was performed to systematically reveal the toxicity of MPDA NPs to five categories of organs after three different exposure routes, including intravenous injection, intramuscular injection, and intragastric administration. Our results uncovered that MPDA NPs could be deposited in various organs in small amounts after intravenous administration, not for the other two exposure routes. The number of differentially expressed genes (DEGs) identified in the heart, liver, spleen, lung, and kidney from the intragastric administration group was from 22 to 519. Similarly, the corresponding number was from 23 to 64 for the intramuscular injection group and was from 11 to 153 for the intravenous injection group. Functional enrichment analyses showed 6, 39, and 4 GO terms enriched for DEGs in intragastric administration, intramuscular injection, and intravenous injection groups, respectively. One enriched pathway was revealed in intragastric administration group, while no enriched pathway was found in other groups. Our results indicated that MPDA NPs produced only slight changes at the transcriptome level in mice, which provided new insights for further clinical application of MPDA NPs.
研究领域:
纳米技术
·
毒理学
·
分子生物学
·
基因组学
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产品关联
DOI
PubMed
高影响因子
Translational Cancer Research
·
2026
·Vol. 15
·期 2
·90
·
IF 2.1
Zhao Yubo,Zhang Digun,Zheng Hongqun,Chen Xuejian,Xu Lishan
Background N6-methyladenosine (m6A) regulators are involved in hepatocellular carcinoma (HCC) development. However, the functions of m6A regulators in HCC have not yet been elucidated. This study aimed to evaluate the potential of m6A methylation regulators as biomarkers and immunotherapeutic targets in HCC. Methods RNA sequencing data were obtained from publicly available databases including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Bioinformatics analysis was conducted, including Kaplan-Meier (KM) survival analysis, univariate and multivariate Cox regression, receiver operating characteristic (ROC) curve analysis and immune-related signatures were assessed using single-sample gene set enrichment analysis (ssGSEA) and drug sensitivity prediction was performed to identify potential small-molecule compounds. In vitro , small interfering RNA (siRNA)-mediated knockdown of selected m6A regulators was performed in three HCC cell lines (HepG2, HuH7 and MHCC-97H). Quantitative polymerase chain reaction (qPCR) and Western blot (WB) were subsequently conducted to validate gene expression changes. Additionally, WB was performed after treatment with candidate drugs to evaluate their functional impact. Results The five upregulated m6A regulators in HCC, KIAA1429, METTL3, PRRC2A, RBMX, and ZC3H3, were related to worse outcomes in HCC. ROC curves showed that m6A regulators could accurately distinguish between normal and HCC tumor tissues. Furthermore, differential m6A regulator expression was affected by immune infiltration. In advanced HCC patients, m6A regulators were important in determining clinical outcomes. Drug response analysis demonstrated m6A regulators as potential therapeutic agents that could be used as guidance for patients with HCC. PCR and WB analysis showed that m6A regulators could act on immune-related sites, interact with immune tolerance, and inhibit it. Conclusions This study indicates that KIAA1429, METTL3, PRRC2A, RBMX, and ZC3H3 may be potential immunotherapeutic targets and biomarkers in HCC.
✓ 已验证
DOI
PubMed
高影响因子
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