ANALYTICAL CHEMISTRY
·
2026
·
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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PHARMACEUTICAL BIOLOGY
·
2023
·
IF 3.8
Jiali Wang,Xianhai He,Zhirong Jia,Aiwen Yan,Kang Xiao,Shuo Liu,Mengjun Hou,Yaling Long,Xuansheng Ding
Context Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Gefitinib is a first-line treatment for NSCLC. However, its effectiveness is hindered by the development of drug resistance. At present, Shenqi Fuzheng injection (SFI) is widely accepted as an adjuvant therapy in NSCLC.Objective This study investigates the molecular mechanism of SFI when combined with gefitinib in regulating cell progression among EGFR-TKI-resistant NSCLC.Materials and methods We established gefitinib-resistant PC9-GR cells by exposing gefitinib escalation from 10 nM with the indicated concentrations of SFI in PC9 cells (1, 4, and 8 mg/mL). Quantitative real-time polymerase chain reaction was performed to assess gene expression. PC9/GR and H1975 cells were treated with 50 ng/mL of interleukin (IL)-22 alone or in combination with 10 mg/mL of SFI. STAT3, p-STAT3, AKT, and p-AKT expression were evaluated using Western blot. The effects on cell proliferation, clonogenicity, and apoptosis in NSCLC cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation and flow cytometry assays.Results SFI treatment alleviated the development of gefitinib resistance in NSCLC. PC9/GR and H1975 cells treated with SFI significantly exhibited a reduction in IL-22 protein and mRNA overexpression levels. SFI effectively counteracted the activation of the STAT3/AKT signaling pathway induced by adding exogenous IL-22 to PC9/GR and H1975 cells. Moreover, IL-22 combined with gefitinib markedly increased cell viability while reducing apoptosis. In contrast, combining SFI with gefitinib and the concurrent treatment of SFI with gefitinib and IL-22 demonstrated the opposite effect.Discussion and Conclusion SFI can be a valuable therapeutic option to address gefitinib resistance in NSCLC by suppressing the IL-22/STAT3/AKT pathway.
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OncoTargets and Therapy
·
2023
·
IF 4
Gang Wang,Yue Jing,Lingsen Cao,Changchang Gong,Zhunan Gong,Xiangrong Cao
Activation of the transcription factor, signal transducers and activators of transcription 3 (STAT3), has been linked to the proliferation and migration of a variety of human cancer cells. These actions occur via the upregulation or downregulation of cell survival and tumor suppressor genes, respectively. Importantly, agents that can suppress STAT3 activation have the potential for use in the prevention and treatment of various cancers. In this study, an Asiatic acid (AA) derivative, N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), is reported to dose dependently suppress constitutive STAT3 activation in gastric cancer cells. This inhibition was mediated by blockade of Janus-activated kinase 2. Additionally, AA-PMe regulated the expression of STAT3-modulated gene products, including cyclin D1, Bax, Bcl-2, c-Myc, and matrix metalloproteinase (MMP)-2 and MMP-9. Finally, transfection with both a STAT3 mimic and an inhibitor reversed the AA-PMe-driven modulation of STAT3 downstream gene products. Overall, these results suggest that AA-PMe is a novel blocker of STAT3 activation and has the potential for the prevention and treatment of gastric cancer.
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Genes & Genomics
·
2022
·Vol. 45
·期 1
·1-11
·
IF 2.164
Cao Qingfei,Ma Jiaji,Li Weitao,Hong Peng,Shen Tong,Tong Ming
Background Guanine nucleotide-binding protein 2 (GNBP2) is a GTPase that has critical roles in host immunity and some types of cancer, but its function in clear cell renal cell carcinoma (ccRCC) is not fully understood. Objective This work explored the role of GNBP2 in ccRCC progression and the underlying molecular mechanism. Methods Two public human cancer databases TNMplot and TISIDB were employed to analyze the expression pattern of GNBP2 during ccRCC progression and the correlation between GNBP2 expression and clinical features of ccRCC patients. GNBP2 functions in ccRCC cells were determined by EdU staining, flow cytometry, scratch wound assay, transwell assay, and xenograft model. Gene expression was evaluated using qPCR, Western blot, immunofluorescence staining, and immunohistochemical staining. Results GNBP2 expression was significantly elevated in ccRCC tissues and increased gradually with the increasing tumor grades. Patients with higher GNBP2 expression had shorter overall survival times. Knockdown of GNBP2 suppressed tumor cell proliferation and cell cycle progression and reduced the capability of migration and invasion, while GNBP2 overexpression exhibited protumor effects. GNBP2 silencing by RNA interference significantly inhibited the tumor growth of tumor-bearing nude mice and decreased the proliferation marker Ki67. Mechanistically, GNBP2 downregulation suppressed the STAT3 signaling transduction, as it reduced the phosphorylation of STAT3 and modulated the expression of the target genes, including c-Myc, MMP2, N-cadherin, and E-cadherin. Conclusion These findings reveal that GNBP2 promotes ccRCC progression by regulating STAT3 signaling transduction, indicating that GNBP2 might be a promising molecular target for ccRCC therapy.
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2019
·Vol. 46
·期 12
·1194-1200
·
IF 2.336
Di Wu,Wei Zhang,Ying Chen,Hong Ma,Mengchang Wang
Multiple myeloma (MM) is a malignancy characterized by the proliferation of malignant plasma cells. Platycodin D (PLD) is a triterpenoid saponin that exerts anti-tumour activity through multiple mechanisms. However, the role of PLD in MM remains unknown. Here, we investigated the effect of PLD on MM cell lines NCI-H929 and U266B1, and elucidated the underlying molecular mechanism. Cell Counting Kit-8 assay showed that the proliferation of NCI-H929 and U266B1 cells was significantly decreased after PLD treatment. Transwell assay confirmed that PLD treatment suppressed migration of NCI-H929 and U266B1 cells. Flow cytometry results indicated that the apoptotic rates of bortezomib (BTZ)-treated NCI-H929 and U266B1 cells were markedly increased after PLD treatment. Western blot analysis revealed that bcl-2 expression was decreased, while bax expression was increased in PLD-treated NCI-H929 and U266B1 cells compared with that in BTZ-treated cells. Furthermore, PLD treatment blocked the activation of nuclear factor-kappa B (NF-κB) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signalling pathways in NCI-H929 cells. Taken together, these data showed that PLD inhibited proliferation and migration, and enhanced chemosensitization to BTZ through inactivation of the NF-κB and JAK2/STAT3 pathways in MM cell lines. These findings indicated that PLD might serve as a novel therapeutic agent for the treatment of MM.
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NEUROPHARMACOLOGY
·
2025
·
IF 4.6
Wei Wang,Yingzhuo Ding,Chunxia Yu,Qingqing Chi,Xia Fu,Mengjiao Deng,Dongxia Duan,Jinbao Wei,Ronghua Ding,Yufei Xi,Qin Li,Le Ma
Neuro-inflammation contributes to neuropathic pain by sensitizing ionic channels. Kinsenoside, a traditional Chinese medicine, has recognized anti-inflammatory properties. However, it remains unclear whether kinsenoside can be used for pain therapy. Network pharmacology analysis revealed that 57 % of its targets are associated with pain, including inflammation and synaptic transmission. The analgesic effects of kinsenoside were confirmed in SNL and formalin rat models, with ED50 values of 47.99 μg and 36.80 μg, respectively. Transcriptome and WGCNA analyses indicated the involvement of cytokine release, anti-inflammatory activity, and synapse enrichment in the blue module. Furthermore, we confirmed that kinsenoside's efficacy was mainly mediated by IL-10 induction, phosphorylation of STAT3, and SOCS3 expression. Pretreatment with kinsenoside significantly inhibited the release of TNF-α, IL-1β, and IL-6. Kinsenoside also attenuated ER stress in both microglia and neural cells. Molecular docking analysis demonstrated significantly high binding energies of IL-10, STAT3, and SOCS3 with MHC. Additionally, whole-cell recordings revealed that bath application of kinsenoside reduced the frequency and amplitude of spinal glutamatergic transmission in a dose-dependent manner. In summary, pharmacological prediction and biological validation collectively indicate that kinsenoside significantly exerts significant analgesic effects by attenuating ER stress and inhibiting inflammatory responses via the IL-10/p-STAT3/SOCS3 axis, precisely regulating spinal glutamatergic transmission for pain relief.
研究领域:
药理学
·
神经科学
·
分子生物学
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Food & Function
·
2024
·
IF 5.1
Yahui Wu,Mona Alrasheed Bashir,Changsheng Shao,Han Wang,Jianxia Zhu,Qing Huang
Numerous natural compounds are recognized for their anti-inflammatory properties attributed to antioxidant effects and modulation of key inflammatory factors. Among them, astaxanthin (AST), a potent carotenoid antioxidant, remains relatively underexplored regarding its anti-inflammatory mechanisms and specific molecular targets. In this study, human monocytic leukemia cell-derived macrophages (THP-1) were selected as experimental cells, and lipopolysaccharide (LPS) served as the inflammatory stimulus. Upon LPS treatment, the oxidative stress was significantly increased, accompanied by remarkable cellular damage. Moreover, LPS escalated the expression of inflammation-related molecules. Our results demonstrated that AST intervention could effectively allevate the LPS-induced oxidative stress, facilitate the cellular repair, and significantly attenuate the inflammation. Further exploration of anti-inflammatory mechanism revealed AST could substantially inhibit the NF-κB translocation and activation, and mitigate the inflammatory factor production by hindering NF-κB through the antioxidant mechanism. We further confirmed that AST exhibited protective effects against cell damage and reduced the injury from inflammatory cytokines by activating p53 and inhibiting STAT3. In addition, utilizing network pharmacology and in silico calculations based on molecular docking, molecular dynamics simulation, we identified interleukin-6 (IL-6) as a prominent core target of AST anti-inflammation, which was further validated by the RNA interference experiment. This IL-6 binding capacity actually enabled AST to curb the positive feedback loop of inflammatory factors, averting the onset of possible inflammatory storms. Therefore, this study offers a new possibility for the application and development of astaxanthin as an popular dietary supplement of anti-inflammatory or immunomodulatory function.
研究领域:
免疫学
·
药理学
·
分子生物学
·
细胞生物学
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Frontiers in Immunology
·
2020
·
IF 5.085
Ma Zhanchuan,Zhen Yu,Hu Cong,Yi Huanfa
Myeloid-derived suppressor cells (MDSC) play a crucial role in regulating the intestinal immune response during colitis. We previously revealed an essential role of MDSC in promoting TH17 cell polarization, which was found to be arginase-1 (Arg-1)-dependent; however, the underlying mechanism remains obscure. Here we report that percentage of MDSC decreased in ArgmyeKO mice during DSS-induced colitis. IL-17A levels reduced but IL-17F levels increased significantly in the colorectum of ArgmyeKO mice, leading to severe tissue damage and high risk of mortality rate. Activation of estrogen receptor (ESR) increased pSTAT3 level in MDSC and consequently led to elevated percentage of MDSC and more Arg-1 and inducible nitric oxide synthase expression in MDSC. Increased level of IL-17A and reduced level of IL-17F alleviated colitis in mice consequently. Together, these findings demonstrate a protective role of MDSC-derived Arg-1 during colitis after activates ESR/STAT3 signaling in MDSC. High level of Arg-1 favors accumulation of IL-17A, but reduced IL-17F expression in the colorectum of mice and ultimately leading to relief of colitis, indicating a potential clinical impact of MDSC-derived Arg-1 for controlling inflammatory bowel disease.
研究领域:
免疫学
·
分子生物学
·
消化病学
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NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 4
·237
·
IF 4.5
Han Zhipeng,Li Xing,Yang Li,Li Jinglin,Zhao Kaiyang,Xie Junxiong,Zhou Siyuan,Shi Wenli,Zhang Xiaolina
Neuropathic pain (NP) is chronic pain caused by injury or disease affecting the nervous system. SIN@Lip-HA was prepared and characterised for particle size, zeta potential, encapsulation efficiency and morphology. Sprague-Dawley rats with spared nerve injury (SNI) were randomly divided into the six groups. Analgesic effects were assessed via behavioural tests. Histopathological changes were examined using H&E staining. Astrocyte polarisation was detected using immunofluorescence, and Western blotting was used to assess related protein expression. qRT-PCR measured mRNA level of genes, while ELISA evaluated inflammatory cytokines and oxidative stress markers. The study showed that the particle size of SIN@Lip-HA was 111 ± 5.13 nm, with an encapsulation efficiency of 85.47% and a zeta potential of -24.86 ± 1.20 mV. The in vitro release profile showed sustained drug release, and the formulation remained stable for 3 months. Compared with the model group, SIN@Lip-HA significantly increased PWT and PWL, alleviated spinal cord pathology and was associated with a shift in astrocyte reactivity, as indicated by a reduction in A1-related markers and an increase in A2-related markers. SIN@Lip-HA downregulated CGRP/SP and GFAP. It was also found to inhibit JAK2/STAT3 pathway activation by reducing p-JAK2/p-STAT3 expression and decrease TNF-α, IL-1β and IL-6 whilst increasing IL-10. It also mitigated oxidative stress. Concomitant use with gabapentin markedly enhanced therapeutic efficacy. These findings suggest that sinomenine liposomes alleviate NP in SNI rats in a manner associated with inhibition of JAK2/STAT3 signaling and correlated with astrocyte reactivity, and reduced pain mediators.
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Biomaterials Science
·
2026
·
IF 6.1
Qinbiao Chen,Yanli Ma,Yuewu Tang,Ni Du
Sepsis-related acute kidney injury (SA-AKI) represents a severe complication associated with elevated mortality rates, primarily driven by imbalanced Th17 immune responses and mitochondrial dysfunction. Consequently, there is an urgent need for a versatile nanomaterial that can enhance mitochondrial performance while also exerting anti-inflammatory effects. A synthetically produced nanoenzyme has the potential to address this challenge. In this study, we created a biomimetic nanozyme (BPQDs@Raw264.7@Kim-1) by engineering clusters of black phosphorus quantum dots (BPQDs) that are coated with macrophage membranes and functionalized with kidney injury molecule-1 (Kim-1) for targeted delivery. This nanozyme improves its antioxidant and anti-inflammatory properties by clustering black phosphorus quantum dots, while the stability of the drug is maintained through encapsulation within Raw264.7 cell membranes. The system effectively achieves homologous targeting via external Kim-1 molecules. The objective of this nanozyme is to modulate the SIRT3/RORγt/STAT3 pathway to reduce Th17-driven inflammation and alleviate SA-AKI. In vitro experiments demonstrated that the nanozyme possesses excellent biocompatibility, efficient cellular uptake, and the ability to scavenge reactive oxygen species (ROS) in LPS-stimulated HK-2 cells. It mitigated mitochondrial injury, decreased apoptosis, and lowered the levels of pro-inflammatory cytokines. Mechanistically, the nanozyme's overexpression of SIRT3 inhibited RORγt/STAT3 signaling, resulting in reduced Th17 differentiation and inflammatory cytokine release. Importantly, silencing SIRT3 negated these therapeutic benefits, underscoring its critical role. This research introduces a targeted nanozyme approach that alleviates SA-AKI by simultaneously restoring mitochondrial balance and suppressing Th17 inflammation through the SIRT3/RORγt/STAT3 pathway, presenting a promising therapeutic strategy for organ injury caused by sepsis.
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Frontiers in Immunology
·
2026
·
IF 5.9
Ruixue Dai,Liangliang Cao,Jiahui Ren,Jingru Liu,Kexin Zhu,Peidong Chen,Weifeng Yao,Xuelong Zhao,Beihua Bao,Li Zhang
Background Excessive inflammation mediated by macrophages impedes wound healing following surgical drainage of perianal abscess, a common yet challenging condition in colorectal surgery. Cayratia japonica ointment (CJO) has shown clinical efficacy, but its active immunomodulatory constituents and mechanisms remain unclear. Methods We evaluated the anti-inflammatory effects of seven CJO-derived flavonoids in LPS-stimulated RAW264.7 macrophages. Skin pharmacokinetics were assessed in mice, and therapeutic efficacy was tested in a rat postoperative perianal abscess model. Molecular mechanisms were investigated via Western blot, RT-qPCR, and molecular docking. Results Pharmacokinetic analysis revealed that apigenin exhibited the highest transdermal exposure among all detected components. In vitro , apigenin significantly suppressed LPS-induced production of IL-6, TNF-α, and IL-1β in RAW 264.7 cells. In vivo , apigenin treatment markedly reduced serum levels of these pro-inflammatory cytokines, attenuated inflammatory cell infiltration, and promoted collagen deposition at the wound site. Mechanistically, apigenin downregulated both the phosphorylation and total protein levels of JAK1 and STAT3, suggesting functional modulation of the JAK1/STAT3 signaling pathway. Conclusion Apigenin may contribute to observed biological effects of CJO that promotes wound healing by attenuating macrophage-driven inflammation through potential modulation of the JAK1/STAT3 signaling pathway, offering a promising natural immunomodulator for postoperative wound management.
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Oncology Letters
·
2022
·Vol. 24
·期 5
·1-9
·
IF 3.111
Yang Chen,Li Hou
It has previously been reported that human hepatocellular carcinoma‑related protein 1 (HCRP‑1), which is a tumor suppressor gene, and epidermal growth factor receptor (EGFR) are abnormally expressed in certain solid tumors. Therefore, in the present study, the expression patterns of HCRP‑1 in oral squamous cell carcinoma (OSCC) are discussed. Moreover, the present study investigated whether HCRP‑1 regulated EGFR expression levels and its downstream effectors to further determine the regulation of tumor cell behavior. Therefore, the expression levels of HCRP‑1 in normal oral epithelial and OSCC cells were determined, and the effects of HCRP‑1 overexpression on OSCC cell proliferation, migration and invasion were assessed. Moreover, the culture medium from the different groups of OSCC cells was separately supplemented into the human umbilical vein endothelial cell (HUVEC) cultures, and the migration and angiogenesis of the HUVECs were assessed. To determine the roles of EGFR/STAT3 in the regulation of HCRP‑1, EGF and colivelin, a STAT3 agonist, were used to treat CAL‑27 cells and their effects on the cells were assessed using the aforementioned functional experiments. The results demonstrated that HCRP‑1 expression levels were downregulated in OSCC cells and that HCRP‑1 overexpression could suppress OSCC cell proliferation, migration and invasion. Moreover, the culture medium from OSCC cells overexpressing HCRP‑1 facilitated the migration and angiogenesis of HUVECs. Furthermore, HCRP‑1 was demonstrated to function in cells by regulating the EGFR/STAT3 signaling pathway. In summary, the present study indicated that HCRP‑1 alleviated the malignant phenotype and angiogenesis of OSCC cells via the downregulation of the EGFR/STAT3 signaling pathway.
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