PHYTOMEDICINE
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2025
·
IF 8.3
Xinyuan Jiang,Zhiyong Xu,Huan Wang,Jiangnan Zhao,Nueraili Maihemuti,Sujing Jiang,Mingshu Xiao,Kaiyue Zhang,Sibei Liang,Yueli Shi,Kai Wang
Background and purpose : As a malignant tumor characterized by a dismal prognosis and a high mortality rate, non-small cell lung cancer (NSCLC) presents significant challenges in contemporary treatment. These challenges include drug resistance and side effects, which severely hamper the effectiveness of current therapeutic strategies. An increasing number of herbal formulas have been utilized in antitumor therapy, owing to their cost-effectiveness, beneficial efficacy, and additional advantages. FuZhengXiaoJi Decoction (FZXJD), a cancer-treating formula, has been successfully applied in NSCLC clinical treatment, but the underlying mechanism remains elusive. Therefore, this paper integrated multiple analytical methods, including network pharmacology, metabolomics, biological approaches, and molecular docking to clarify how FZXJD suppresses NSCLC. Methods : This study assessed the anti-NSCLC efficacy of FZXJD using in vitro assays and lung cancer xenograft models, and the primary components and potential mechanisms of FZXJD inhibition of NSCLC were identified by high-performance liquid chromatography (HPLC) and network pharmacology. Subsequently, inhibitory mechanisms of FZXJD and its principal effector component oleanolic acid (OA) on NSCLC were explored by molecular docking, as well as biological experiments. Finally, effects of FZXJD on critical metabolic pathways in tumors were further investigated by metabolomics and metabolite enrichment analysis. Results : Inhibition of FZXJD on NSCLC cells was confirmed in vitro experiments. Correspondingly, in vivo experiments revealed that FZXJD impeded tumor progression without obvious toxic side effects. Network pharmacology and molecular docking disclosed that target genes involved in FZXJD’s inhibition of NSCLC were significantly enriched in the PI3K/AKT and ERK/MAPK signaling pathways. Additionally, 14 core genes (HSP90AA1, VEGFA, AKT1, JUN, EGFR, CASP3, ESR1, ERBB2, STAT3, MTOR, SRC, MDM2, CCND1, MAPK3) as well as the main component of the antitumor effect of FZXJD, the OA, were also identified. Biological experiments and molecular docking demonstrated that FZXJD and OA exerted antitumor effects by inhibiting two significant pathways, PI3K/AKT and ERK/MAPK. Metabolomics analysis indicated that FZXJD treatment suppressed glutathione metabolism in vivo. Conclusion FZXJD and its main active ingredient, OA, impede NSCLC progression by inhibiting PI3K/AKT and ERK/MAPK signaling pathways. FZXJD treatment also markedly attenuates glutathione metabolism. This research provides a promising strategy for the application of herbal formulas in NSCLC.
研究领域:
肿瘤学
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中药学
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生物信息学
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药理学
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DOI
PubMed
高影响因子
VIEW
·
2025
·
IF 8.5
Na Sun,Zhaowenbin Zhang,Jiajing Wang,Yuan Yang,Jianhui Wang,Tianxing Chen,Yiqi Wang,Haodong Xiao,Ping Gu,Zhaoyang Wang,Jiang Chang,Jing Ji
Retinal degenerative diseases, primarily owing to the gradual loss of neuronal cells, could lead to blindness. Transplantation of retinal progenitor cells (RPCs), which had the unique ability to differentiate into neuronal cells, offered promising therapeutic potential for these diseases. However, a critical challenge in stem cell therapy was the efficient promotion of the directed proliferation and differentiation of progenitor cells. To overcome this limitation, we formulated a zinc silicate bioceramic (ZS) composite hydrogel. The experimental outcomes demonstrated that this novel material possessed substantial advantages and immense possibilities for mimicking the extracellular matrix environment, thereby effectively modulating stem cell proliferation and differentiation. Notably, it enhanced the differentiation of RPCs into neurons while suppressing glial cell differentiation. In particular, ZS had an exceptional capacity to induce the differentiation of RPCs into photoreceptor cells, a specialized type of neuronal cell. It was important to highlight that the ZS composite hydrogel predominantly facilitated the differentiation of RPCs through activation of the Tiam2-Rac signaling pathway. Concurrently, it stimulated proliferation via activation of the AKT and ERK signaling pathways. The Zn ions in the ZS composite hydrogel primarily promoted the proliferation of RPCs, while the synergistic effect of Zn ions and Si ions contributed to reducing inflammatory factor expression and promoting the neuronal differentiation of RPCs. In conclusion, the meticulous modulation of RPC proliferation and differentiation mediated by ZS bioceramics held promise for novel therapeutic strategies of retinal degenerative diseases and neurodegenerative disorders.
研究领域:
生物医学工程
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眼科研究
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再生医学
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高影响因子
CHEMICAL PAPERS
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2024
·Vol. 78
·期 14
·7943-7950
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IF 2.1
Li Zhigang,Liu Xuzhuo,Wang Chunlong,Song Hanbing,Zhang Jie
In this study, we synthesized zinc selenide (ZnSe)-polyacrylamide (PAM) nanomaterials for their potential application in treating knee osteoarthritis (KOA). Initially, we characterized the newly prepared material through various techniques including Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and nitrogen adsorption–desorption to confirm its identity as the desired product. The results demonstrated that ZnSe-PAM nanomaterial exhibited excellent water solubility, biocompatibility, and stability, along with a large surface area, making it suitable for use as a drug carrier. Subsequently, the material was loaded with the drug 1 to obtain ZnSe-PAM@1. Cellular and thermosensitive experiments were then conducted, revealing that this nanomaterial could facilitate drug release by generating heat, thereby reducing the level of microRNA-146a-5P and blocking the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/extracellular (PI3K/Akt/mTOR/ERK) signal-regulated kinase signaling pathway, thus alleviating the symptoms of KOA. These findings present a new direction for drug intervention in KOA and highlight the potential of developing ZnSe-PAM nanomaterials as novel drug carriers.
研究领域:
材料科学
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医学
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生物技术
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DOI
高影响因子
Biomaterials Advances
·
2024
·
IF 5.5
Hu Hui,Yuheng Song,Hongmei Liu,Jiahui Fan,Zhou Sha,Hongchuang Li,Jian Lu,Qian Zhang,Xiang Fei,Meifang Zhu
Artificial periosteum is deemed a novel strategy for inducing endogenous bone regeneration, but ideal periosteum substitutes achieved by orchestrating a biomimetic microenvironment for bone regeneration remain a significant challenge. Here, we design and fabricate a hybridized nanofiber-based artificial periosteum with boosted osteoinduction properties. Via a “molecular cage” biomineralization strategy, nano-hydroxyapatite (nano-HAp) with a controllable size (∼22 nm) and excellent dispersion serves as unique nano-additives for water-soluble polyvinyl-alcohol (PVA)-based artificial periosteum. The PVA/HAp composite is electrospun into nanofibers to replicate the extracellular-matrix-inspired nanostructure for inducing cell adhesion, proliferation, and fate manipulation. A simple post-crosslinking treatment is subsequently applied to further booster its mechanical strength (6.6 MPa) and swelling stability. The optimized sample of C-PVA/HAp (10 wt% nano-HAp) artificial periosteum features excellent biocompatibility and remarkable in vitro mineralization. Cell experiments demonstrate that its effectively boasted cell modulation for enhanced osteogenesis without the aid of growth factors, showing a possible activation of the ERK/MAPK signaling pathway. This work provides an effective strategy for designing novel HAp nano-additives and expands the possibility of biomimetic fabrication for more advanced nanofiber-based artificial periosteum.
研究领域:
生物材料
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组织工程
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骨再生
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纳米技术
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Jing-Yu Feng,Jing-Ling Yang,Rui Zhang,Kiran Thakur,Jian-Guo Zhang,Jianbo Xiao,Zhao-Jun Wei
DT-13 potently inhibits CRC metastasis with a favorable biosafety profile. • Plectin (PLEC) is identified as the direct intracellular binding target of DT-13. • DT-13 occupies the PLEC CH domain to physically disrupt the PLEC-TPM4 interactome. • Target engagement down-regulate TPM4 and suppresses Akt/ERK-driven EMT programs. Background Metastasis is the leading cause of colorectal cancer (CRC) mortality. Standard 5-fluorouracil (5-FU) has limited anti-metastatic efficacy and dose-dependent toxicities, underscoring the need for therapeutic alternatives with improved safety profiles. Methods This study investigated the anti‑metastatic mechanism of Liriope muscari baily saponins C (DT‑13) in CRC. Cell viability, migration, and invasion were assessed in HCT116 cells. An orthotopic CRC model was established in BALB/c nude mice to compare the therapeutic efficacy and hematological safety of DT-13 against 5-FU. Direct targets of DT-13 were identified using chemical proteomics (small‑molecule pull‑down, cellular thermal shift assay, drug affinity responsive target stability assay) and molecular dynamics simulations. Results DT-13 inhibited HCT116 proliferation (IC 50 ∼19 μM) and reduced migration and invasion by 78% and 90% in vitro. In vivo , DT-13 achieved a comparable reduction in tumor volume to 5-FU (21% of control volume), while exhibiting a favorable safety profile. Chemical proteomics identified plectin (PLEC) as a primary direct target of DT-13. Molecular docking revealed a binding affinity of –7.654 kcal/mol. Mechanistically, DT-13 occupied the calponin homology domain of PLEC, disrupting its interaction with tropomyosin-4 (TPM4). This led to TPM4 downregulation and subsequently inhibition of Akt and ERK signaling pathways, thereby suppressing the epithelial-mesenchymal transition process. Conclusion DT‑13 exerts anti-metastatic effects in CRC by disrupting the PLEC/TPM4 cytoskeletal scaffold. DT-13 achieved potent anti-metastatic efficacy with a significantly improved systemic safety profile compared to 5-FU. These findings highlight the clinical potential of DT-13 as a safer therapeutic alternative for patients with metastatic CRC. Download: Download high-res image (126KB) Download: Download full-size image
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NATURAL PRODUCT RESEARCH
·
2026
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IF 1.8
Lin Zhang,Guanke Liu,Bingyang Zhang,Shiqing Song,Xiao Liu,Tie Yao,Feng Qiu,Feng Zhao
Two new secoiridoid glycosides, gentscaside A (1) and gentscaside B (2), were isolated along with three known compounds gentiopicroside (3), rindoside (4), gentiotrifloroside (5), from the Rhizomes of Gentiana scabra. The structures of the new compounds were determined by comprehensive NMR analysis, and their absolute configurations were determined on the basis of detailed spectroscopic analyses and acidic hydrolysis. The five compounds were evaluated for their anti-inflammatory activity (NO inhibitory activity in LPS-stimulated macrophages). Compounds 1, 4 and 5 showed significant inhibitory effects on LPS-induced NO release in RAW 264.7 cells. The IC50 values are 2.15 μM, 3.02 μM and 6.87 μM, respectively. Additionally, the potential anti-inflammatory mechanism of the active new compound 1 was explored.
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PubMed
高影响因子
PLoS One
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2014
·Vol. 9
·期 4
·e94418
·
IF 3.534
Wu Li,Quanju Zhao,Wanyan Deng,Tian Chen,Minqiang Liu,Jianping Xie
Intracellular survival plays a central role in the pathogenesis of Mycobacterium tuberculosis , a process which depends on an array of virulence factors to colonize and replicate within the host. The M. tuberculosis iron regulated open reading frame (ORF) rv3402c , encoding a conserved hypothetical protein, was shown to be up-regulated upon infection in both human and mice macrophages. To explore the function of this ORF, we heterologously expressed the rv3402c gene in the non-pathogenic fast-growing Mycobacterium smegmatis strain, and demonstrated that Rv3402c, a cell envelope-associated protein, was able to enhance the intracellular survival of recombinant M. smegmatis . Enhanced growth was not found to be the result of an increased resistance to intracellular stresses, as growth of the Rv3402c expressing strain was unaffected by iron depletion, H 2 O 2 exposure, or acidic conditions. Colonization of macrophages by M. smegmatis expressing Rv3402c was associated with substantial cell death and significantly greater amount of TNF-α and IL-1β compared with controls. Rv3402c-induced TNF-α and IL-1β production was found to be mediated by NF-κB, ERK and p38 pathway in macrophages. In summary, our study suggests that Rv3402c delivered in a live M. smegmatis vehicle can modify the cytokines profile of macrophage, promote host cell death and enhance the persistence of mycobacterium within host cells.
研究领域:
微生物学
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免疫学
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DOI
高影响因子
FITOTERAPIA
·
2023
·
IF 3.4
Bike Zhang,Dan Su,Yonggui Song,Huizhen Li,Changlian Chen,Liangliang Liao,Hongjie Zhang,Jian Luo,Ming Yang,Genhua Zhu,Zhifu Ai
Phytochemical investigation of the volatile oil of Yueju (YJVO) and its constituent herbs induced the detection of 52 compounds in YJVO, mainly monoterpenes and sesquiterpenes as well as a small amount of aromatic and aliphatic compounds. 5 of these compounds were found only in the YJVO instead of the volatile oil of its constituent herbs. The anti-depressant effect of YJVO was proved by behavioral tests in chronic unpredictable mild stress (CUMS) mice. An acute oral toxicity evaluation determined the LD 50 of YJVO was 5.780 mL/kg. Doppler ultrasound and laser speckle imaging have detected that the YJVO could improve depression-related cerebral blood flow. In addition, related neurotransmitters and proteins were analyzed through targeted metabolomics and immunofluorescence. The potential antidepressant mechanisms of YJVO related to significantly decreasing Glu in CUMS mice by up-regulating the ERK/AKT-mediated expression of GLT-1.
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高影响因子
Cell Death Discovery
·
2023
·Vol. 9
·期 1
·1-15
·
IF 7
Ye Jianfeng,Liu Wangmin,Yu Xueyang,Wu Lina,Chen Zhengjie,Yu Yufei,Wang Jianfeng,Bai Song,Zhang Mo
Homeobox A5 (HOXA5), a homeodomain transcription factor, is considered a tumor suppressor in cancer progression; however, its function in prostate cancer (PCa) remains unclear. This study focused on the relevance of HOXA5 in PCa progression. We identified the downregulation of HOXA5 in PCa tissues based on the TCGA database and further verified in 30-paired PCa and adjacent normal tissues. Functional studies revealed that HOXA5 upregulation impaired the stem-like characteristics and malignant behaviors of PCa cells in vitro and in vivo. Mechanistically, HOXA5 was found to be regulated by tumor necrosis factor receptor-associated factor 7 (TRAF7), a putative E3-ubiquitin ligase. We observed that TRAF7 was overexpressed in PCa and subsequently enhanced the degradation of HOXA5 protein via its ubiquitin ligase activity, contributing to the acquisition of an aggressive PCa phenotype. For its downstream mechanism, we demonstrated that sprouty RTK signaling antagonist 2 (SPRY2) served as a downstream target of HOXA5. HOXA5 could directly bind to the SPRY2 promoter, thereby regulating the SPRY2-mediated MEK/ERK signaling pathway. Silencing SPRY2 largely compromised the tumor-suppressive effect of HOXA5 in PCa progression and cancer stemness. Our findings highlight the previously-underappreciated signaling axis of TRAF7–HOXA5–SPRY2, which provides a novel prognostic and therapeutic target for PCa treatment.
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PubMed
高影响因子
Journal of Applied Biomedicine
·
2023
·Vol. 21
·期 4
·193-199
·
IF 1.3
Hongji Wang,Lisha Chen,Juping Xing,Xiangchao Shi,Changshui Xu
Naringin inhibits inflammation and oxidative stress, the P2 purinoreceptor X4 receptor (P2X4R) is associated with glial cell activation and inflammation, the purpose of this study is to investigate the effects of naringin on P2X4 receptor expression on satellite glial cells (SGCs) and its possible mechanisms. ATP promoted the SGC activation and upregulated P2X4R expression; naringin inhibited SGC activation, decreased expression of P2X4R, P38 MAPK/ERK, and NF-κB, and reduced levels of Ca2+, TNF-α, and IL-1β in SGCs in an ATP-containing environment. These findings suggest that naringin attenuates the ATP-induced SGC activation and reduces P2X4R expression via the Ca2+-P38 MAPK/ERK-NF-κB pathway.
研究领域:
神经科学
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药理学
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细胞生物学
·
炎症研究
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DOI
PubMed
高影响因子
JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
·
2025
·
IF 4.1
Lu-an Weng,Luojun Zheng,Dengke Meng,Xin Zhang,Diwen Shou
BackgroundIncreasing evidence suggests that herbal-derived exosome-like nanoparticles (ELNs) can easily cross biological barriers such as the blood-brain barrier (BBB). However, current understanding of ELNs application in ischemic stroke therapy is still in its infancy.MethodWe extracted nanoparticles (TGD-NPs) from Tianma Gouteng decoction (TGD) and characterized their morphology and main active compounds. Subsequently, the potential and functional mechanism of TGD-NPs in maintaining the integrity of the BBB were evaluated in middle cerebral artery occlusion (MCAO)-induced ischemic stroke model and oxygen-glucose deprivation/reperfusion (OGD/R)-stimulated cell model.ResultWe successfully extracted NPs, which retains the main bioactive compounds of TGD: baicalin, emodin, gastrodin, and stachydrine. Functional studies indicated that in mouse MCAO model, TGD-NPs intervention was more effective than TGD preparations in maintaining the integrity of the BBB, reducing the infarct area, and improving the neurological function. Meanwhile, TGD-NPs treatment attenuated the decrease in cell viability caused by OGD/R, and it significantly enhanced expression of tight junction proteins (Occludin and ZO-1). Mechanistic exploration revealed that TGD-NPs markedly upregulated lncRNA OIP5-AS1 expression, and its beneficial effect was attributed to the activation of the S1PR1-ERK1/2-MEK1/2 signaling axis.ConclusionTGD-NPs are positive in maintaining BBB integrity and neurological function after ischemic stroke.
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Pingchuan Wang,Tianming Li,Changping Niu,Siyu Sun,Dongyan Liu
Reactive oxygen species (ROS) damage to the intestinal barrier is a side effect of prolonged hyperoxia therapy in neonates, which impairs growth and development of the intestine and promotes intestinal diseases. However, the research on clinical prevention and treatment is lacking. Therefore, we investigated the molecular mechanisms of the neonate intestinal response against hyperoxia-derived ROS to find targets for intestinal barrier damage prevention. Human intestinal epithelial cells were incubated under hyperoxia (85% oxygen) to build an in vitro model. ROS and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway were inhibited to detect the MAPK/ERK pathway, nuclear factor erythroid factor 2-related factor 2 (Nrf2), hypoxia-inducible factor-1α (Hif-1α), and interleukin-17D (IL-17D) expression. Nrf2 was inhibited to detect Hif-1α and IL-17D expression. Hif-1α was inhibited to detect Nrf2, IL-17D, and tight junction proteins expression and apoptosis. Cells were treated with human recombinant IL-17D to detect TNF-α, IL-1β, IL-10, and tight junction proteins expression. ROS, Nrf2, Hif-1α, and IL-17D were upregulated and the MAPK/ERK pathway was activated under hyperoxia. But ROS inhibition downregulated the MAPK/ERK pathway, Nrf2, Hif-1α, and IL-17D. MAPK/ERK pathway inhibition downregulated Nrf2, Hif-1α, and IL-17D. Nrf2 inhibition downregulated Hif-1α and IL-17D. Hif-1α inhibition downregulated Nrf2, IL-17D, tight junction proteins, and exacerbated apoptosis. The recombinant IL-17D downregulated TNF-α, IL-1β, but upregulated IL-10 and tight junction proteins. We concluded that Hyperoxia-generated ROS activated the MAPK/ERK pathway to regulate Nrf2, Hif-1α, and IL-17D expression. Nrf2 and Hif-1α were interdependent and promoted IL-17D. Importantly, Hif-1α and IL-17D expression protected the intestinal epithelial barrier.
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高影响因子
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