SENSORS AND ACTUATORS B-CHEMICAL
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2022
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IF 9.221
Mei Wang,Hanfeng Cui,Nian Hong,Qingxia Shu,Xinru Wang,Yuping Hu,Guobing Wei,Hao Fan,Jing Zhang
In this paper, we first synthesized a novel tetraferrocene signal marker. Then a reagentless triplex DNA junctions-based electrochemical DNA sensor using signal amplification strategy of CHA and tetraferrocene was constructed. Tetraferrocene labeled hairpin probes (H1 and H2) were integrated together to form triplex DNA junctions through connecting chain (C1). It enabled catalytic hairpin assembly (CHA) reaction to be initiated without the addition of exogenous probe during the detection process, and the conformational change of the target caused the change of electrochemical signal. Combined with tetraferrocene and CHA strategies, the sensor achieved double signal amplification with a detection limit as low as 0.085pM. In addition, the sensor was successfully applied to mRNA detection in cells with high sensitivity and reagentless operation, providing possibilities for in vivo testing.
研究领域:
生物化学
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分子生物学
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分析化学
·
生物技术
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DOI
高影响因子
RSC Medicinal Chemistry
·
2024
·
IF 4.1
Die Zhang,Wenping Wang,Huiping Ou,Jinhua Ning,Yingxun Zhou,Jin Ke,Anguo Hou,Lingyun Chen,Peng Li,Yunshu Ma,Wenbin Jin
To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of novel chalcone analogues were designed and synthesized. In vitro anti-inflammatory activity of these compounds has been evaluated by screening inhibitory effects of the NO production in RAW264.7 cell lines. The most promising compounds 3h and 3l were selected to further investigated by assessment of their dose-dependent inhibitory activity against cytokines such as TNF-α, IL-1β, IL-6, and PGE2 release. The further study also indicated that 3h and 3l could significantly suppress expressions of iNOS and COX-2 through NF-κB/JNK signaling pathway. Furthermore, compounds 3h and 3l could also remarkably inhibit the mRNAs expressions of inflammation-related genes. Docking simulation was conducted to position compounds 3h and 3l into the iNOS binding site to predict the probable binding mode. In conclusion, a series of chalcone analogues with reasonable drug-likeness obtained by in silico rapid prediction could be used as promising lead candidates.
研究领域:
药理学
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炎症研究
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药物发现
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DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2024
·
IF 2.9
Yifei Shen,Jie Liu,Bingyi Yao,Yuanjin Zhang,Shengbo Huang,Chenmeizi Liang,Junze Huang,Yu Tang,Xin Wang
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, which can cause serious complications and gradually increase the mortality rate. However, the effects of NAFLD on drug-metabolizing enzymes and transporters remain unclear, which may cause some confusion regarding patient medication. In this study, a NAFLD rat model was constructed by feeding rats with methionine and choline deficiency diets for 6 weeks, and the mRNA and protein levels of drug-metabolizing enzymes and transporter were analyzed by real-time fluorescent quantitative PCR and Western blot, respectively. The activity of drug-metabolizing enzymes was detected by cocktail methods. In the NAFLD rat model, the mRNA expression of phase I enzymes, phase II enzymes, and transporters decreased. At the protein level, only CYP1A1, CYP1B1, CYP2C11, and CYP2J3 presented a decrease. In addition, the activities of CYP1A2, CYP2B1, CYP2C11, CYP2D1, CYP3A2, UGT1A1, UGT1A3, UGT1A6, and UGT1A9 decreased. These changes may be caused by the alteration of FXR, HNF4α, LXRα, LXRβ, PXR, and RXR. In conclusion, NAFLD changes the expression and activity of hepatic drug-metabolizing enzymes and transporters in rats, which may affect drug metabolism and pharmacokinetics. In clinical medication, drug monitoring should be strengthened to avoid potential risks.
研究领域:
药理学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2025
·
IF 12.5
Jing Chen,Yuan Ma,Zhi-Min Rao,Song-Lin Jiang,Ying-Jun Lou,Karim Malik,Arman Chowdhury,Hua-Zhong Ying,Chen-Huan Yu
The development of potent adjuvants is crucial for enhancing influenza mRNA vaccine efficacy. Tremella aurantia polysaccharides possess bioactivities, but their structural complexity and adjuvant potential remain unclear. In this study, a high-molecular-weight (Mw: 1178.77 kDa) polysaccharide (TAP) was purified from T. aurantia fruit bodies and hydrolyzed by using an ultrasonic-assisted H 2 O 2 -Cu 2+ method, yielding three products (designated TAP1-TAP3). Structural analyses revealed that TAP1 (426.28 kDa) and TAP2 (16.96 kDa) retained the native monosaccharide composition (Man, GlcA, Xyl, Fuc), whereas TAP3 (21.97 kDa) lost its fucose residues. All polysaccharides shared a 1,3-α-D-mannose backbone with GlcA and Xyl side chains. TAP2, a novel low-Mw fucosylated glucuronoxylomannan, exhibited superior immunostimulatory activity in vitro with minimal cytotoxicity. When used as an adjuvant with a seasonal influenza HA mRNA vaccine in mice, TAP2 significantly enhanced hemagglutination inhibition titers, increased influenza-specific IgG levels, and improved survival rates against a lethal influenza virus challenge. Mechanistically, the immunoenhancing effect of TAP2 was attributed to its optimal molecular size and sulfated fucose branches, which potently promoted dendritic cell maturation primarily via activation of the TLR4/MyD88/NF-κB pathway. This study not only identified TAP2 as a promising adjuvant candidate for mRNA vaccines but also elucidated the structure-activity relationship of Tremella glucuronoxylomannans.
研究领域:
免疫学
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糖生物学
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疫苗学
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多糖化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2025
·
IF 4.1
Jiayi Xiao,Qi Li,Zhu Li,Lingxin Kong,Yang Shang,Yongliang Xu,Mo Dong,Sijin Zhang,Zitao Li,Caijuan Li
Breast cancer (BC) remains a leading cause of cancer-related mortality in women worldwide. Through online data mining, we identified the significant upregulation of the RNA-binding protein La Ribonucleoprotein 1 (LAR1) in BC. Functionally, LAR1 knockdown impeded S-phase entry, migration, and invasion of BC cells in vitro . Consistently, it markedly suppressed tumor growth and liver metastasis in BALB/c nude mice. Mechanistically, LAR1 promoted AKT phosphorylation and IκBα degradation, leading to NF-κB activation, with the NF-κB inhibitor PDTC rescuing LAR1's effects. Integrated analysis of transcriptome and previous data of LAR1-mRNA interactome revealed Apolipoprotein C1 (APOC1) as a key target. LAR1 bound to the APOC1 3'-UTR to stabilize its mRNA, and APOC1 overexpression counteracted the effects of LAR1 knockdown. In conclusion, our study defines the LAR1-APOC1-NF-κB axis as a crucial driver of BC progression, offering a promising therapeutic strategy for BC treatment.
研究领域:
肿瘤学
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分子生物学
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细胞信号传导
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癌症遗传学
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RNA生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Yue Wu,Xiaoyu Liang,Canquan Mao,Yuhong Jiang
mRNA antigens require powerful nanocarriers for efficient delivery, as well as immunomodulators for controlling their excessive immunogenicity. While lipid nanoparticles (LNPs) used in mRNA vaccines exhibited systemic toxicity, there is an urgent need for developing potential nanoparticles with strong immunoenhancing effects for mRNA antigens. Although natural polysaccharides as adjuvants assisted various types of antigens in triggering potent immune responses, they have been rarely investigated in mRNA vaccines. Here, we constructed four polysaccharide nanoparticles with different molecular weights (MWs) to deliver and protect mRNA antigens, and boosted antigen cross-presentation, DC maturation, CD4+/CD8+T cell responses and humoral immune responses. Importantly, the immunoenhancing capacities of polysaccharide nanoparticles were highly dependent on their MW properties. CS NPs with high MW initiated stimulator of interferon genes (STING)-mediated autophagy and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome signaling, consequently possessing superior mRNA antigen-specific immune responses in vitro and in vivo. In contrast, CS NPs with low MWs induced NLRP3 signaling without STING or autophagy activation, which failed to induce robust immune responses. Therefore, it uncovered the MW-dependent immunoenhancing effects and mechanism of polysaccharide nanoparticles, providing a platform for designing potential nanosized polysaccharide immunomodulators for mRNA vaccines.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2023
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IF 4
Feier Cheng,Yaru Yang,Shaojun Yun,Jinling Cao,Mingchang Chang,Yanfen Cheng,Cuiping Feng
Sparassis latifolia polysaccharide (SLP) has broad application prospects as a raw material of functional food. This study aimed to investigate the effects of SLP on liver cholesterol metabolism and its mechanism. Sprague–Dawley rats were fed a high-fat, high-cholesterol diet, and various assessments were conducted including hematoxylin and eosin staining, measurement of liver and metabolic indices, and antioxidant analysis. In addition, fluorescence quantitative reverse transcription-polymerase chain reaction was performed to analyze mRNA expression, and gas chromatography-mass spectrometry was employed for screening differential metabolites. The results demonstrated that SLP reduced the abnormal increase in the liver index caused by high fat and cholesterol and improved liver tissue morphology, metabolism level, and antioxidant-related enzyme activities. The polysaccharide regulated the liver sterol metabolism pathway, decreased the mRNA expression levels of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoAR) and sterol O-acyltransferase 1 (SOAT1), upregulated the mRNA expression levels of cholesterol 7α hydroxylase (CYP7α-1) and ABCA1, and increased the contents of propionic acid and butyric acid in the liver. These findings indicated a novel pathway through which SLP prevented hepatic lipid deposition and ameliorated sterol metabolism via regulating the HMG-CoAR-CYP7α-1 axis.
研究领域:
营养学
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生物化学
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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
高影响因子
PHARMACEUTICAL BIOLOGY
·
2020
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IF 2.971
Xuemei Liu,Deliang Liu,Youyou Shuai,Huilin Li,Hengxia Zhao,Xin Qu,Shufang Chu,Xuewen Zhang
Context HuoxueJiangtang decoction (ZY) is a traditional Chinese medicine for the treatment of diabetes.Objective The protective effect of ZY on renal injury in diabetic nephropathy rats was investigated in this study.Materials and methods Fifty 4-week-old SPF Wistar male rats were selected to construct diabetic nephropathy model rats (DN) group by continuous high-fat feeding for 4 weeks, followed by a tail vein injection of 30 mg/kg streptozotocin for 1 week. The experimental rats were divided into six groups of 10 rats: normal (control), DN, DN + ZY, DN + metformin, DN + metformin + ZY, and DN + metformin + captopril (positive control) groups. Among the groups, 6.25 g/kg ZY, 250 mg/kg metformin, and 17.5 mg/kg captopril were given to the rats by gavage once a day for 16 weeks. Blood glucose, dietary behaviour, biochemical indicators, and gene expression changes were measured in each group.Results Metformin + ZY treatment significantly lowered blood glucose, water intake, urine total protein, urine albumin, urine volume, serum triglyceride, and serum cholesterol levels in the DN group. The pathological changes of kidney tissue showed that the DN + metformin + ZY group had a protective effect on kidney tissue damage. And ZY and metformin + ZY treatments repaired the expression of genes in the DN group.Discussion and conclusion The ZY and metformin combined treatment showed a clear therapeutic effect on kidney damage in DN. This study provides a potential mechanism for the treatment of diabetic nephropathy with ZY combined with metformin.
研究领域:
中医药学
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糖尿病研究
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肾脏病学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2026
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IF 7.3
Chao Murilege,He Miao,Cai Yongliang,Yin Feifan,Chen Jinhua,Pan Han,Cheng Wenting,Wang Zhongyun,Xiang Yang
Obesity is a major global health concern that substantially
increases
the risk of metabolic disorders. Signal Transducer and Activator of
Transcription 3 (STAT3) plays a pivotal role in the progression of
obesity by promoting the whitening of brown adipose tissue. In this
study, a novel and highly sensitive strategy for STAT3 mRNA detection
was developed by integrating three-way junction (3WJ)-mediated strand
displacement amplification (SDA) with rolling circle amplification
(RCA). The 3WJ structure enables specific target recognition through
a proximity effect, enabling accurate discrimination of STAT3 mRNA
and triggering primary signal amplification via SDA. The resulting
SDA products serve as primers to initiate RCA, achieving secondary
signal amplification while eliminating the need for exogenous primers
and effectively reducing background signals. This method enables femtomolar
(fM)-level detection of target mRNA and exhibits excellent selectivity
and stability in complex biological matrices. Overall, the proposed
strategy provides a reliable analytical platform for sensitive STAT3
mRNA analysis and broadens its potential applications in obesity research.
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产品关联
DOI
高影响因子
Clinical and Translational Medicine
·
2025
·Vol. 15
·期 3
·e70250
·
IF 6.8
Kaixiang Li,Runjiao Luo,Xindi Yu,Wei Dong,Guoliang Hao,Dan Hu,Ziyou Yu,Minglu Liu,Tingting Lu,Xiangying Wang,Xin Tang,Xinjun Lin,Huijing Wang,Wei Wang,Wei Fu
Mesenchymal stem cell therapy involves the secretion of various factors to regulate the local microenvironment in various of diseases. This therapy offers hope for treating acute myocardial infarction (MI), which poses a serious threat to human health. However, challenges such as low paracrine efficiency and poor cell survival persist due to the harsh post-infarction conditions, such as hypoxia. Recently, enhanced cell therapy, in which vascular endothelial growth factor A (VEGFA) and basic fibroblast growth factor (bFGF) are used as therapeutic agents to limit myocardial injury and simultaneously induce neovascularisation, has been recognised as a promising new strategy to improve the efficacy of cell therapy. Chemically synthetic modified messenger RNA (modRNA), a novel protein expression technology, enables safe, rapid, efficient and pulsatile expression of target proteins in vivo and in vitro settings. It has been widely applied in the fields of vaccine research and tissue regeneration. In this study, human adipose-derived stem cells (hADSCs) were transfected with VEGFA and bFGF modRNA to transiently overexpress these proteins before transplantation. This modification enhanced the paracrine effect of transplanted hADSCs and promoted stability in the vascular network at the transplantation site. Overexpression of VEGFA and bFGF in hADSCs not only inhibited apoptosis but also reduced ventricular remodelling and improved cardiac function and left ventricular conduction. Overall, the additive effects of VEGFA modRNA, bFGF modRNA and hADSCs hold promise for comprehensive cardiac repair post-MI and show substantial potential for treating ischemic heart diseases. Key points ModRNAs-transfected hADSCs exhibit pulsed and transient expression, enabling efficient production of functional VEGFA and bFGF proteins. Intracardiac injection of these engineered hADSCs leads to the enhancement of cardiac function and the improvement of electrical conduction. The hADSCs dual mainly exerts its effect on myocardial infarction by promoting stable vascular regeneration and suppressing cell apoptosis.
研究领域:
干细胞治疗
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心脏病学
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分子生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
Microbiome
·
2025
·Vol. 13
·期 1
·1-17
·
IF 12.7
Liu Youhua,Liu Jiaqi,Ren Ruiti,Xin Zimeng,Luo Yaojun,Chen Yushi,Huang Chaoqun,Liu Yuxi,Yang Tongyudan,Wang Xinxia
Background Although short-term high-fat diet (S-HFD) and long-term high-fat diet (L-HFD) induce metabolic disorder, the underlying epigenetic mechanism is still unclear. Results Here, we found that both 4 days of S-HFD and 10 weeks of L-HFD increased mRNA m 6 A level in epididymal white adipose tissue (eWAT) and impaired metabolic health. Interestingly, S-HFD activated transposable elements (TEs), especially endogenous retroviruses (ERVs) in eWAT, while L-HFD activated long interspersed elements (LINEs). Subsequently, we demonstrated that both S-HFD and L-HFD increased m 6 A level of Ehmt2 and decreased EHMT2 protein expression and H3K9me2 level, accounting for activation of ERVs and LINEs. Overexpression of EHMT2 in eWAT or inhibition of ERVs and LINEs by antiviral therapy improved metabolic health under HFD feeding. Notably, we found that both short-term and long-term HFD feeding increased Fimicutes/Bacteroidota ratio and decreased the gut microbiome health index. Fecal microbiota transplantation (FMT) experiments demonstrated that gut microbiota from S-HFD and L-HFD was responsible for increased m 6 A level in eWAT, resulting in glucose intolerance and insulin insensitivity. Furthermore, we identified that both S-HFD and L-HFD increased the abundance of the gut microbial metabolite homogentisic acid (HGA), and HGA level was positively correlated with unclassified_f__Lachnospiraceae which was both increased in S-HFD and L-HFD feeding mice. Administration of HGA increased the m 6 A level of Ehmt2 and decreased the EHMT2 protein expression and H3K9me2 level in eWAT, leading to metabolic disorder in mice. Conclusions Together, this study reveals a novel mechanism that S-HFD and L-HFD induce metabolism disorder through gut microbiota-HGA-m 6 A- Ehmt2 -ERV/LINE signaling. These findings may provide a novel insight for prevention and treatment of metabolism disorder upon short-term or long-term dietary fat intake.
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研究领域:
分子生物学
·
营养学
·
微生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2022
·
IF 4.631
Meng Zhang,Yi Liu,Jing Chen,Lei Chen,Li Zhang,Xianguo Chen,Zongyao Hao,Chaozhao Liang
Background Chronic nonbacterial prostatitis (CNP) has a high incidence, low cure rate, and unclear pathogenesis. Here, we aimed to systematically identify effective diagnostic and therapeutic targets for CNP.Methods Prostate tissues were obtained from established mouse models and negative controls and were used for mRNA array sequencing and immunohistochemistry (IHC) staining. Predominant pathways were identified based on pathway enrichment analysis and pharmaceutical experiments. We also investigated the functional role of CXCL12 on CP, a critical factor belonging to the predominant chemotaxis pathway, and employed IHC staining to explore the influence of the CXCL12/CXCR4 axis on the activation of the NF-κB, AKT, and STAT3 signaling pathways. Serum samples derived from both CNP cases and healthy controls were used to determine the secretion level of CXCL12.Results By employing mRNA array sequencing and immunohistochemistry, we found that CXCR4, CXCL12, CD44, and OFLM4 were highly expressed in the infiltrated inflammatory T cells of the prostate tissues generated from CNP mice, while they were rarely expressed on the epithelial cells. Based on the pathway enrichment results, we applied pathway inhibitors to suppress the activity of these classic pathways. We found that targeting the CXCL12/CXCR4 axis with its specific antagonist AMD3100 remarkably alleviated inflammatory infiltration of the prostate in CNP models. Similar results were obtained when we replaced AMD3100 with adenovirus-associated virus (AAV)-shCxcl12. To clarify the potential mechanisms of how the CXCL12/CXCR4 axis influences the pathogenesis of CNP, we tested the classical downstream pathways. The results suggested that p-Akt, p-STAT3, and p-NF-κB were more highly expressed on the inflammatory cells of the prostate derived from the CNP model and were partly suppressed after applying AMD3100 or delivering AAV-shCxcl12, indicating that the CXCL12/CXCR4 axis potentially functioned through AKT/NF-κB and STAT3 signaling to influence the pathogenesis of CNP.Conclusion Our study provides potential diagnostic biomarkers and therapeutic targets for CNP.
研究领域:
免疫学
·
分子生物学
·
药理学
·
泌尿学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）