INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Zhen He,Xiangyun Tan,Ming Yuan,Liang Chen,Yan Meng,Qi Wang,Junjie Hu,Zhenpeng Qiu,Yuan Yang
Acute liver injury (ALI) is a prevalent form of hepatic disease associated with significant morbidity and mortality due to medical treatments, exposure to toxins or viral infections. Anethole trithione (ATT) is a heterocyclic sulfur compound recognized for its chemoprotective properties against cancer and drug-induced toxicity. This study aimed to evaluate the effectiveness of ATT in the treatment of ALI. The therapeutic effects of ATT on hepatic injury were evaluated in vivo by inducing ALI in mice through the administration of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). Additionally, HepG2 and Huh7 cells exposed to LPS were utilized to investigate the underlying mechanisms in vitro. The results indicated that ATT significantly reduced the production of reactive oxygen species (ROS), mitigated oxidative stress-related biochemical markers, and inhibited hepatocyte apoptosis in vivo, resulting in marked improvement in ALI in the murine model. Mechanistic studies conducted both in vivo and in vitro demonstrated that ATT alleviates LPS/D-Gal-induced ALI by inhibiting ROS production and the activity of nuclear factor-kappa B (NF-κB). Collectively, these findings underscore the potential therapeutic benefits of ATT in the management of ALI.
研究领域:
药理学
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肝脏病学
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免疫学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2016
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IF 4.758
Keqin Deng,Chunxiang Li,Haowen Huang,Xiaofang Li
An electrochemical biosensor based on specific protein-DNA binding and rolling circle amplification (RCA) signal enlargement was developed for transcription factor (TF) detection. The TF biosensor was constructed by three oligo-DNA probes. Probe 1 (P1) was immobilized on gold electrode. Probe 2 (P2) hybridized with P1 to form a partially complementary double-stranded DNA . The complementary part contained a TF binding sequence, while the non-complementary part of P2 integrated a RCA primer sequence. Probe 3 (P3) can displace P2 by hybridizing with P1 to produce a completely complementary double-stranded DNA. When TF protein was introduced, a stable TF-DNA complex would form and the displacement reaction mentioned above was hindered, which made the RCA possible. Finally, the electrochemical redox probe methylene blue (MB) was bound to the RCA product and offered the available detection signal. Using nuclear factor kappa B (NF-κB) p65 as a model target, the fabricated electrochemical biosensor exhibited a wide linear region and a low detection limit.
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
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DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
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2022
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IF 12.545
Feng Qiu,Xiaoyan Gan,Jianglong Yao,Bingying Jiang,Ruo Yuan,Yun Xiang
Transcription factors (TFs) are key substances in regulating the transcription, replication and expression of genes, and the detection of TFs can provide valuable information to diagnose a variety of diseases. By integrating hybridization chain reaction (HCR)-activated Cas12a enzyme with bio-responsive DNA hydrogels, we propose a dual amplification and label-free homogeneous electrochemical detection method to realize sensitive nuclear factor-kappa B p50 (NF-κB p50) detection. The presence of the target molecules protects the DNA duplex probes from digesting by exonuclease III and initiates HCR to generate long double stranded DNAs that can activate the activity of RNA-guided Cas12a enzymes. The single-stranded region of the DNA linkers that crosslink the DNA hydrogels can be cleaved by the activated Cas12a to release a large number of electroactive substances embedded in the gels, which exhibit highly enhanced electrochemical signals for detecting target molecules at the detection limit of 54.1 fM. In addition, the successful interrogation of NF-κB p50 spiked into lysate of HeLa cells by such method is also verified. The established method thus shows new opportunities for sensitive and convenient monitoring of other transcription factors and biomarkers.
研究领域:
生物化学
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分子生物学
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医学诊断
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DOI
PubMed
高影响因子
Translational Oncology
·
2022
·
IF 4.803
Yongxiu Du,Yanlan Yang,Wenbo Zhang,Chenxi Yang,Pu Xu
Oral squamous cell carcinoma (OSCC) is a usual oral cancer. Therefore, it's essential to identify targets for its early diagnosis and therapy. This research aimed to explore the roles of human β-defensin-3 (hBD-3) and nuclear factor-kappa B (NF-κB) p65 in the pathogenesis and progression of OSCC. The connection between NF-κB p65 and the carcinogenesis of oral cancer was analyzed by immunohistochemical staining. The relative expressions of hBD-3 and NF-κB p65 in OSCC cells were evaluated by qRT-PCR and Western blot. Afterward, hBD-3 was knocked down, and NF-κB p65 was overexpressed. The cell viability and invasion were tested via CCK-8 and Transwell experiment, and the expression of hBD-3, NF-κB p65, and its downstream molecules was evaluated by Western blot. The expression of NF-κB p65 was increased with the aggravation of the oral submucosal fibrosis. HBD-3 and NF-κB p65 were high-expressed in OSCC cells. The viability and invasion abilities of OSCC cells that knocked down hBD-3 were markedly decreased, while they were restored by the overexpression of NF-κB p65. The expressions of NF-κB p65 and c-myc were diminished while IκB and p21 were raised with the knockdown of hBD-3. After overexpression of NF-κB p65, the expression of hBD-3 and IκB did not change markedly, while c-myc was increased and p21 was decreased dramatically. HBD-3 and NF-κB p65 facilitate the proliferation and invasion of OSCC cells, and hBD-3 may promote this process by governing the expression of NF-κB p65 and its downstream c-myc and p21.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Animal Nutrition
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2023
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IF 6.3
Linglian Kong,Yuanli Cai,Xue Pan,Chuanpi Xiao,Zhigang Song
Medium-chain fatty acids and their derivatives are natural ingredients that support immunological functions in animals. The effects of glycerol monolaurate (GML) on intestinal innate immunity and associated molecular mechanisms were investigated using a chicken embryo model. Sixty-four Arbor Acres broiler embryos were randomly allocated into four groups. On embryonic day 17.5, the broiler embryos were administered with 9 mg of GML, which was followed by a 12-h incubation period and a 12-h challenge with 32 μg of lipopolysaccharide (LPS). On embryonic day 18.5, the jejunum and ileum were harvested. Results indicated that GML reversed the LPS-induced decline in villus height and upregulated the expression of mucin 2 ( P < 0.05). GML decreased LPS-induced malondialdehyde production and boosted antioxidant enzyme activity ( P < 0.05). GML alleviated LPS-stimulated intestinal secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) ( P < 0.05). GML also normalized LPS-induced changes in the gene expression of Toll-like receptor 4, nuclear factor kappa-B p65 ( NF-κB p65 ), cyclooxygenase-2, NOD-like receptor protein 3, IL-18 , zonula occludens 1, and occludin ( P < 0.05). GML enhanced as well the expression of AMP-activated protein kinase α1 and claudin 1 ( P < 0.05). In conclusion, GML improved intestinal morphology and antioxidant status by alleviating inflammatory responses and modulating NF-κB signaling in LPS-challenged broiler embryos.
研究领域:
动物科学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Huxuan Gong,Xiao Tan,Jiaojiao Hou,Zan Gong,Xiangxiang Qin,Jing Nie,Hua Zhu,Shian Zhong
In this study, ACP-1, a water-soluble polysaccharide was isolated from the roots of Alocasia cucullata (AC) using freeze-thaw treatment (FTT). Structural characterization revealed ACP-1 (2.10×10 5 Da) to be a homogeneous heteropolysaccharide primarily consisting of glucose, galactose, and arabinose, and a trace of fucose, rhamnose, and glucuronic acid. Methylation analysis and nuclear magnetic resonance spectroscopy revealed that the backbone of ACP-1 consisted of →[3)-β-D-Gal p -(1] 4 →3,6)-β-D-Glc p -(1→3,6)-β-D-Glc p -(1→, with a branch at C-3. In vitro experiments demonstrated that ACP-1 significantly enhanced the proliferation and phagocytosis of RAW264.7 cells, upregulated the expression of co-stimulatory molecules (CD80 and CD86), and activated RAW264.7 cells via the nuclear factor kappa-B signal transduction pathway, resulting in nitric monoxide release and the secretion of the cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Overall, ACP-1 shows potential as a novel immunostimulant.
研究领域:
生物化学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
Therapeutic Delivery
·
2018
·Vol. 9
·期 4
·
IF 0
Ya Xiao,Jiajia Huang,Jiajia Xu,Liuwei Zeng,Jiaran Tian,Yunru Lou,Yuxue Liu,Bo Hu,Fei Tong,Ruilin Shen
Aim: To synthesize a puerarin nanoparticle based on glycyrrhetinic acid (GA)-PEG-PBLA and evaluate it in vivo. Materials & methods: In this study, drug nanoparticle was synthesized, characterized and assessed as puerarin delivery system. Nanoparticle GA-PEG-PBLA could combine with puerarin via hydrophobic interaction to form the compound. Puerarin could be quickly and efficiently loaded via the nanoparticle GA-PEG-PBLA at pH 7.4. Further, GA-PEG-PBLA-mediated puerarin delivery system could target for the liver that had GA receptor binding. The antiliver ischemia/reperfusion injury role of puerarin/GA-PEG-PBLA was measured in rats using free puerarin and puerarin/PEG-PBLA as the controls. Results: GA-PEG-PBLA displayed efficient loading and sustained release. Puerarin/GA-PEG-PBLA showed strengthened antiliver ischemia/reperfusion injury characteristics. Conclusion: Overall, the results show that GA-PEG-PBLA could be regarded as an underlying puerarin nanoparticle.
研究领域:
药理学
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肝脏病学
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产品关联
DOI
PubMed
PHYTOMEDICINE
·
2025
·
IF 8.3
Wanfen Liao,Aiwen Dong,Fatima Hafeez,Qinyong Ye,En Huang
Background Celastrol (CEL), a bioactive compound isolated from Tripterygium Wilfordii Hook. F, exerts neuroprotective effects through anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms in several neurodegenerative diseases, including Parkinson's disease (PD). CEL covalently binds to the thiol group of cysteine residues in cell division cycle 37 (CDC37), leading to redox-dependent modulation of CDC37 function. However, whether CEL redox regulates CDC37 and CEL-CDC37 interaction plays a role in pathogenesis of PD is still not be investigated yet. This study aids to demonstrate the role of CEL redox regulation of CDC37 in an MPTP-induced mouse model of PD. Methods Lentiviral vectors were used to overexpress or knock down CDC37 in MPTP-injected mice. CEL was administered to assess its effect on CDC37 redox status and related molecular pathways. Results CDC37 overexpression alleviated MPTP-induced motor deficits and dopaminergic neuron loss, whereas CDC37 knockdown exacerbated these impairments. Overexpression of CDC37 also suppressed activation of the NF-κB pathway and reduced phosphorylation of α-synuclein at serine 129 (p-S129-syn). MPTP insult decreased the reduced (active) form of CDC37 due to oxidative stress. CEL treatment restored CDC37 redox status, improved locomotor performance, preserved dopaminergic neurons, and inhibited both NF-κB activation and p-S129-synuclein levels. These effects were mediated by CEL's redox regulation of CDC37, which prevented its overoxidation, disrupted the Hsp90/CDC37 complex, and suppressed downstream pro-inflammatory and pro-pathogenic signaling. Conclusion Our study suggests that CEL restores the protective role of CDC37 in the MPTP-injected Parkinson's disease (PD) mouse model via redox regulation of CDC37, which prevents over-oxidation of CDC37 under high oxidative stress, and disrupts the Hsp90/CDC37 complex and subsequently blocks NF-κB pathway activation and p-S129-synuclein production. This study might provide a promising strategy for PD and further understanding of the therapeutic mechanism of CEL application.
研究领域:
神经退行性疾病
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药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2025
·Vol. 13
·期 9
·e70881
·
IF 3.8
Zhuohui Luo,Zaibin Xu,Kongyan Wang,Huiyu Hu,Jiawen Huang
Citri Sarcodactylis Fructus (CSF), an ornamental and edible fruit belonging to the genus Citrus in the Rutaceae family, has been shown to exhibit anti‐inflammatory, antioxidant, and anti‐obesity effects. However, its impact on the progression of acute lung injury (ALI) remains unclear. In this study, CSF significantly alleviated LPS‐induced pulmonary edema in ALI mice and improved oxidative stress markers, as evidenced by reduced serum malondialdehyde (MDA) levels and increased serum superoxide dismutase (SOD) levels. It also decreased macrophage and neutrophil counts as well as protein levels in bronchoalveolar lavage fluid (BALF), and inhibited inflammatory responses‐specifically, it reduced the protein and gene expression of IL1β, IL6, and TNF‐α in lung tissues, downregulated the mRNA levels of chemokines, and suppressed LPS‐induced activation of NF‐κB signaling. Moreover, CSF significantly reduced NLRP3 inflammasome activation. The components of CSF exhibit high binding activity and stability to NF‐κB p65 or NLRP3, along with low binding free energy, within their respective binding pockets. This study reveals that CSF alleviates LPS‐induced ALI by inhibiting NF‐κB signaling and NLRP3 inflammasome activation‐mediated inflammatory response, thereby providing a scientific basis for the utilization of CSF resources. Citri Sarcodactylis Fructus (CSF) has been shown to exhibit anti‐inflammatory, antioxidant, and anti‐obesity effects. However, its impact on the progression of acute lung injury (ALI) remains unclear. This study reveals that CSF alleviates LPS‐induced ALI by inhibiting NF‐κB signaling and NLRP3 inflammasome activation‐mediated inflammatory response, thereby providing a scientific basis for the utilization of CSF resources.
研究领域:
药理学
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免疫学
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植物学
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分子生物学
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呼吸系统疾病
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2023
·Vol. 16
·期 12
·1655
·
IF 4.6
Isoo Youn,Sujin Han,Hee Jin Jung,Sang Gyun Noh,Hae Young Chung,Yean Kyoung Koo,Sunhye Shin,Eun Kyoung Seo
Perilla frutensevar.acuta(Lamiaceae) has been used to treat indigestion, asthma, and allergies in traditional medicine. In this study, luteolin 7-O-diglucuronide (1), apigenin 7-O-diglucuronide (2), and rosmarinic acid (3) were isolated from the leaves ofP. frutescensvar.acutathrough various chromatographic purification techniques. Several approaches were used to investigate the anti-inflammatory activity of the constituents (1–3) and their working mechanisms. In silico docking simulation demonstrated that1–3would work as a PPAR-α/δ/γ agonist, and in vitro PPAR-α/δ/γ transcriptional assay showed that thePerillawater extract (PWE) and3increased PPAR-α luciferase activity (1.71 and 1.61 times of the control (PPAR-α + PPRE,p< 0.001)). In the NF-κB luciferase assay,1suppressed NF-κB activity the most (56.83% at 5 µM; 74.96% at 10 µM; 79.86% at 50 µM). In addition,1and2inhibited the mRNA expression of NF-κB target genes, includingIl6,Mcp1, andTnfa, at 50 µM, and3suppressed the genes at the mRNA level in a dose-dependent manner. We report that1and2exert anti-inflammatory effects through NF-κB inhibition, and the PPAR-α/NF-κB signaling pathway is related to the anti-inflammatory activity of3.Keywords:Perilla frutescensvar.acuta;anti-inflammation;peroxisome proliferator-activated receptor;nuclear factor kappa B;flavonoid diglucuronide
研究领域:
药理学
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植物化学
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分子生物学
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DOI
PubMed
高影响因子
CytoJournal
·
2025
·
IF 3.1
Yanan Xu,Yanbo Wang,Wenyue Zhao,Fengli Liu
Objective:
Cisplatin (DDP)-based chemotherapy medications are frequently used as the initial line of treatment for cancer patients, including those with stomach cancer. At present, DDP resistance is a frequent problem in chemotherapy for advanced gastric cancer (GC). This study aimed to investigate the function of NPC intracellular cholesterol transporter 2 (NPC2) in GC cells.
Material and Methods:
The expression of NPC2 and baculoviral inhibitor of apoptosis repeat containing 3 (BIRC3) in gastric epithelial cells-1, BGC823, and BGC823/DDP cells was determined by Western blotting and quantitative real-time polymerase chain reaction, respectively. Subsequently, the proliferative capacity and viability of BGC823 cells were assessed by 3-(4,5-dimethylthiazol2-yl)-2.5-diphenyl-2-tetrazolium bromide, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, and colony-formation assay. Finally, the association of NPC2 and BIRC3 with the nuclear factor kappa-B (NF-κB) pathway was determined by Western Blot.
Results:
In GC cells, NPC2 transcription increased, and DDP-resistant cells showed higher NPC2 expression levels than their parental cells (P < 0.001). In terms of mechanism, compared with parental cells, overexpressing NPC2, DDP-resistant cells showed resistance to DDP. Knocking down NPC2 increased the apoptotic response of DDP-resistant cells to DDP and blocked the cancer cells resistant to DDP exhibiting BIRC3, thereby promoting GC cell apoptosis (P < 0.001). Importantly, involving NF-κB signaling overturned the NPC2-mediated DDP resistance.
Conclusion:
NPC2 regulated BIRC3 and affected drug resistance in GC. Therefore, NPC2 and BIRC3 may be new targets for cancer patient treatment following DDP therapy and act as roadblocks to overcome chemotherapy resistance in GC.
Keywords: Baculoviral inhibitor of apoptosis repeat containing 3, Gastric cancer, Nuclear transcription factor-κB
CAS / MDL:
研究领域:
肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Jiewei Zheng,Xin Yang,Cong Zhang,Weipeng Zhang,Yue Hu,Lihai Zeng,Lili Liu,Guoliang Li
Icariin (ICA), an active ingredient found in Epimedium , possesses antioxidant and anti-inflammatory properties and has garnered widespread attention in recent years. This study investigated the protective effects of ICA against cadmium (Cd)-induced kidney injury in rats. Healthy male specific pathogen-free Sprague–Dawley rats were randomly divided into a control group, Cd group, a low-dose ICA group, a middle-dose ICA group, and a high-dose ICA group using a random number table. Tissue and blood samples were analyzed for renal function markers, histopathology, and gene expression. We found that ICA intervention ameliorates Cd-induced nephrotoxicity by enhancing glomerular filtration, mitigating renal tubular epithelial cell damage, reducing cellular degeneration and edema, and decreasing oxidative stress. ICA demonstrated anti-apoptotic activity through the regulation of pro- and anti-apoptotic gene transcription and by inhibiting apoptosis, thus protecting the kidneys. ICA also exhibited anti-inflammatory effects by reducing the transcription of Cd-induced pro-inflammatory genes, inhibiting nucleotide oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome formation, and preventing pyroptosis. ICA potentially regulated the Toll-like receptor 4/ P2rx7 /nuclear factor kappa B signaling pathway, which modulated the activation of the NLRP3 inflammasome and contributed to its anti-inflammatory action. ICA reduced Cd-induced renal injury in rats, likely through a mechanism involving antioxidant, anti-apoptotic, and anti-inflammatory effects.
研究领域:
药理学
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毒理学
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分子生物学
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肾脏生理学
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DOI
PubMed
高影响因子
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