Pharmaceuticals
·
2026
·Vol. 19
·期 7
·1043
·
IF 5.7
Xiaoxuan Mo,Fan Gao,Jiaye Tian,Fengyue Xu,Zeyang Xie,Hongyan Wei,Jinhu Yang,Jianming Jiang,Guoxing Deng,Qiuhong Guo
Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory and gastrointestinal protective effects in clinical practice; however, its active constituents and mechanisms of action against CAG remain undefined. This study aimed to clarify the absorbed bioactive components of LHHZ and explore its therapeutic mechanism for CAG.Methods: Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was employed to identify the absorbed components of LHHZ in the gastric and intestinal tissues of mice. The therapeutic effects of LHHZ on CAG were assessed through histopathological staining, ultrastructural observation, and evaluation of serum and gastric functional indicators. Network pharmacology, molecular docking, and molecular dynamics simulations were integrated to predict the core targets and key signaling pathways, while the regulatory effects on the interleukin-17 (IL-17) signaling pathway were further validated by immunofluorescence staining, real-time quantitative polymerase chain reaction, and Western blotting. Additionally, 16S ribosomal RNA gene sequencing and targeted metabolomics were applied to investigate the effects of LHHZ on gut microbiota composition and short-chain fatty acid (SCFA) metabolism.Results: The results revealed that 55 and 48 absorbed components were identified in the gastric and intestinal tissues, respectively, predominantly derived fromCoptis chinensisFranch. andPogostemon cablin(Blanco) Benth. LHHZ significantly alleviated gastric mucosal lesions, reduced intestinal metaplasia, restored the ultrastructure of gastric mucosal cells, improved gastric functional indicators including pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (GAS-17), and decreased the levels of pro-inflammatory cytokines. Network pharmacology combined with in vitro and in vivo experiments demonstrated that the core bioactive components of LHHZ can target and regulate interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), attenuate activation of the IL-17 signaling pathway, and suppress the secretion of downstream pro-inflammatory factors. Furthermore, LHHZ enhanced the alpha diversity of gut microbiota, reduced the Firmicutes to Bacteroidetes (F/B) ratio, restored the abundance of SCFA-producing bacteria such as Bacteroidales and Oscillospirales, and normalized the aberrant levels of eight SCFAs. Significant correlations were also observed between gut microbiota composition and SCFA metabolism.Conclusions: These findings suggest that LHHZ alleviates CAG by inhibiting inflammation via the IL-17 signaling pathway and by modulating the gut microbiota–SCFA axis, thereby providing preclinical evidence supporting its further investigation and development for multi-target therapeutic strategies against CAG.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Jia Liang,Xiangqing Hei,Lu Chen,Zhenhua Zou,Yuke Ji,Lujia Feng,Wangting Li,Yijing Zhuang,Bingyu Bai,Renxue Liang,Yunyun Zou,Pan Xiao,Qiang Lin,Huiyan Zheng,Dong Fang,Wei Chi,Shaochong Zhang
Photoreceptor degeneration is a major cause of irreversible visual impairment worldwide, most notably in retinitis pigmentosa (RP). Here, we developed a dual-targeted therapeutic nanoplatform by loading black phosphorus quantum dots (BPQDs) into human dental pulp mesenchymal stem cell-derived exosomes (hDPSC-Exos) and surface-modifying with cell-penetrating peptide transactivated transcription (TAT) and photoreceptor-specific peptide MH42, namely TAT/MH42-engineered black phosphorus quantum dot-loaded exosomes (M/T-BPQD@Exos). M/T-BPQD@Exos showed typical exosomal morphology and good uniformity. In vitro, M/T-BPQD@Exos effectively protected 661 W photoreceptor cells against N-methyl-N-nitrosourea (MNU) injury. In vivo, M/T-BPQD@Exos specifically accumulated in the outer nuclear layer (ONL) and significantly preserved retinal structure and visual function in MNU-induced photoreceptor degeneration rats. Biosafety assessment confirmed no obvious systemic toxicity and inflammation. Mechanistically, M/T-BPQD@Exos alleviated calcium overload, maintained mitochondrial integrity, and suppressed mitochondrial apoptosis by regulating Bcl-2, Bax, and cleaved caspase-3. This study provides a safe and precise strategy for photoreceptor protection in retinal degenerative diseases.
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PHYTOMEDICINE
·
2026
·
IF 11.3
Zihan Mai,Yiyuan Zheng,Jiali Xie,Yi Wen,Shuye Wang,Yuancheng Huang,Haojie Tan,Jingming Chen,Changlong Wang,Yang Tao,Qiuming Chen,Fengbin Liu,Yimin Liang,Xu Chen,Yingpan Zhao,Peiwu Li,Zehong Yang
Background Chronic atrophic gastritis (CAG) with intestinal metaplasia (IM) constitutes a critical intermediate stage in the progression from chronic non-atrophic gastritis (CNAG) to intestinal-type gastric cancer (GC), for which effective therapeutic strategies remain unavailable. JianPi QingRe HuoXue Formula (JQHF), an empirical prescription of traditional Chinese medicine (TCM), has been widely applied in the clinical management of CAG with IM; however, its underlying mechanisms of action remain incompletely elucidated. Purpose This study aims to evaluate the therapeutic efficacy of JQHF in the treatment of CAG with IM and to clarify its mechanism. Methods The main components of JQHF were identified by UPLC-MS/MS, and its potential pharmacological effects were investigated via network pharmacology. The therapeutic efficacy of JQHF were evaluated in clinical patients, animal models, and cell models, followed by validation of the key pathways and targets. Differentially expressed genes (DEGs) between IM and CNAG were identified from the GEO database and further validated by IHC across the CNAG - CAG - IM. Molecular docking and molecular dynamics simulations were performed to characterize the interactions between the main components of JQHF and CDH17. In addition, patient samples collected before and after JQHF treatment, as well as a CDH17-knockdown mouse model established via tail vein injection of adeno-associated virus (AAV), were used to verify changes in CDH17 expression and to elucidate its potential mechanism of action. Results UPLC-MS/MS identified 21 main components of JQHF. Network pharmacology suggested JQHF is involved in the regulation of apoptosis and the Notch pathway. Clinical evaluation demonstrated that JQHF significantly improved gastric mucosal pathological changes in CAG with IM patients, without causing significant adverse effects. Both in vivo and in vitro experiments demonstrated JQHF effectively alleviated the severity of CAG with IM by inhibiting the Notch pathway and inducing apoptosis. Bioinformatic analysis of GEO database revealed CDH17 expression was significantly elevated in IM compared to CNAG, which was further confirmed by IHC across different disease stages. Molecular docking and dynamics simulations demonstrated favorable binding affinities between the main components of JQHF and CDH17, with Astragaloside IV exhibiting the strongest binding affinity. Furthermore, JQHF treatment suppressed CDH17 expression in gastric mucosal samples from patients, concomitantly inhibited the Notch pathway, and promoted apoptosis. These mechanisms were further validated using a CDH17-knockdown mouse model. Notably, CDH17 gene knockdown also attenuated the therapeutic efficacy of JQHF, suggesting CDH17 plays a critical role in mediating the pharmacological effects of JQHF. Conclusions JQHF exerts a positive therapeutic effect on CAG with IM without causing significant adverse effects. Its mechanism of action appears to involve targeting CDH17 to modulate the Notch pathway and induce apoptosis.
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Journal of the Chinese Medical Association
·
2026
·
IF 2.3
Madeti Yelizhati,Chong Xiaoyi,Zhang Xiaotian
Background: The lack of specific and immunocompetent gastric cancer models has hindered the exploration of gastric adenocarcinoma (GAC). We constructed a spontaneous and transplantable GAC model using a genetically engineered mouse. Methods: We generated a tamoxifen-inducible CRISPR-based Anxa10-CreERT2 mouse line and crossed it with the KrasG12D/+ and Tp53R172H/+ strains to develop Anxa10-CreERT2; KrasG12D/+; Tp53R172H/+ mice on a C57BL/6J background. Tamoxifen and N-methyl-N-nitrosourea were administered to induce in situ tumor development. An orthotopic gastric tumor was confirmed by histological analysis and positron emission tomography/computed tomography. A transplantable mouse-derived allograft (MDA) model and stable GAC cell line (ST-YC19) were subsequently established using MDA. The malignant characteristics and drug responses were evaluated. Results: Spontaneous GAC had a 100% incidence within 2.5 months, was predominantly of the intestinal type, and presented essential molecular features of the CIN subtype. The ST-YC19 GAC cell line derived from MDAs exhibited an aggressive phenotype, robust tumorigenic potential, peritoneal dissemination, and distant metastasis. This model showed limited sensitivity to anti-programmed death-1 immunotherapy. Conclusion: We successfully established a spontaneous GAC model and its corresponding cell line in C57BL/6J mice, enabling a comprehensive investigation of tumor progression, metastasis, therapeutic response, and resistance mechanisms in vivo. This model represents a valuable platform for advancing precision medicine in gastric cancer. Lay Summary: Stomach cancer research has been hindered by the lack of realistic animal models that mimic the growth and response of human tumors to treatments. To address this, we created a new mouse model using genetic engineering to develop stomach cancer spontaneously, similar to that in humans. By activating specific cancer-causing gene changes in mice, tumors formed reliably within 2.5 months. These tumors can be transplanted into healthy mice or grown as cell lines in the laboratory, thereby allowing us to study how cancer spreads and test therapies. The model demonstrated resistance to a widely used immunotherapy (anti-programmed death-1), highlighting its usefulness in exploring why some treatments fail. This breakthrough provides a powerful tool for studying stomach cancer progression, testing new drugs, and personalizing treatments for patients, bringing us closer to achieving better outcomes for this deadly disease.
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Animal Cells and Systems
·
2023
·
IF 2.9
Weiming Yan,Yan Sun,Yutong Wang,Wangjiao Liang,Yuxin Xia,Weihua Yan,Meizhu Chen,Tao Chen,Dongliang Li
Upregulation of Sirtuin Type 1 (SIRT1), a nicotinamide adeninedinucleotide (NAD+)-dependent deacetylase, has been proved to protect against ample ocular diseases, while its effect on retinitis pigmentosa (RP) has not been illustrated. The study was aimed to explore the impacts of resveratrol (RSV), a SIRT1 activator, on the photoreceptor degeneration in a rat model of RP induced by N-methyl-N-nitrosourea (MNU), an alkylation. The rats were induced RP phenotypes via the intraperitoneal injection of MNU. The electroretinogram was conducted and revealed that RSV could not prevent the decline of retinal function in the RP rats. The optical coherence tomography (OCT) and the retinal histological examination were performed and showed that the reduced thickness of the outer nuclear layer (ONL) was not preserved by RSV intervention. The immunostaining technique was applied. Afther the MNU administration, the number of the apoptotic photoreceptors in the ONL throughout the retinasand the number of microglia cells present among the outer part throughout the retinas were not significantly reduced by RSV. Western blotting was also performed. The data showed that the level of SIRT1 protein was decreased after MNU administration, while RSV was not able to obviously alleviate the downregulation. Our data together indicated that RSV was not able to rescue the photoreceptor degeneration in the MNU-induced RP rats, which might be due to the MNU-induced consumption of the NAD+.
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PHYTOMEDICINE
·
2023
·
IF 7.9
Yulin Qi,Lu Liu,Dan Liang,Shiyun Tang,Xiaoyi Yu,Hejiang Ye,Nianzhi Chen
Background Retinitis pigmentosa (RP) refers to a group of progressive photoreceptor degenerative diseases . The activation of microglia has been reported to play an important role in the photoreceptor degeneration in RP retinal. Bujing Yishi tablets (BJYS), a Chinese herbal medicine , has been used to treat retinal diseases in China with desirable effect in improving visual function. However, the mechanisms underlying the efficacy of BJYS treatment in RP are not yet fully understood. Purpose Based on the preliminary experiments, this study aimed to investigate the therapeutic mechanism involved in treating N -Methyl- N -Nitrosourea (MNU)-induced retinal degeneration of RP with BJYS. Methods To explore the efficacy of BJYS, a rat experimental RP model was established through intraperitoneal injection of MNU (50 mg/kg). Two experiment was carried out. After the treatment, we conducted H&E, TUNEL , retinal cytokine levels and IBA-1 expression in microglia to confirm the impact on RP model. The specific mechanism of action of BJYS tablet was assessed by western blot , real-time polymerase chain reaction (RT-PCR), and immunofluorescence to determine the mRNA and protein expression levels involved in clarifying the effectiveness of BJYS exerted through P2X7R/CX3CL1/CX3CR1 pathway. Results Significant alleviation of retinal morphological structure and photoreceptor degeneration by BJYS treatment was observed in the retinal of MNU-induced RP rats, BJYS prevented the reduction of ONL thickness and decreased the level of apoptotic cells in ONL. It also inhibited microglia overactivation and reduced retinal levels of IL-1β, IL-6, TNF-α. In addition, BJYS decreased the protein expression and mRNA expression of P2X7, CX3CL1 and CX3CR1 and reduced the phosphorylation of p38 MAPK . Conclusion In summary, this study suggested that BJYS treatment could alleviate photoreceptors degeneration of RP by inhibiting microglia overactivation and inflammation through the P2X7R/CX3CL1/CX3CR1 pathway. These effects suggest that BJYS tablets may serve as a promising oral therapeutic agent for RP.
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高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2021
·Vol. 199
·期 10
·3728-3736
·
IF 3.738
Han Gaochao,Tan Zhuangsheng,Jing Haiming,Ning Junyu,Li Zinan,Gao Shan,Li Guojun
Due to the wide application of rare-earth elements (REEs) in the last decades, lanthanum has increasingly entered the environment and has gradually accumulated in the human body through the food chain. Lanthanum is worth paying attention in terms of food safety. Although the genotoxicity of lanthanum has been studied in vitro, data on its DNA damage in vivo rodent are limited, moreover, which have also presented some controversy. This study aimed to conduct an in vivo rodent alkaline comet assay, and as a companion test to the lanthanum nitrate carcinogenicity test. We conducted an oral gavage experiment for 180 days (26 weeks) to test for the persistence of DNA damage of long-term low-dose accumulation of lanthanum nitrate (12.5, 25, and 50 mg/kg body weight), in F1 hybrid C57-ras transgenic mice (CB6F1) by using alkaline comet assay in the blood and liver. The comet assay revealed that all the tested concentrations of lanthanum nitrate did not induce DNA damage in any of the tissues investigated, whereas DNA damage was induced in the positive control group. These results could indicate that lanthanum nitrate can accumulate in tissues and organs of the mice after exposure, and does not possess DNA damage in C57-ras transgenic mice after repeated treatments at oral doses up to 50 mg/kg·BW for 26 weeks; also, it did not cause pathological changes in the liver of the mice.
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JOURNAL OF NANOPARTICLE RESEARCH
·
2020
·Vol. 22
·期 6
·1-16
·
IF 2.132
Liu Ying,Liu Susu,Wu Meiyu,Lv Jianjun,Yang Yanwei,Dan Mo,Liu Lin,Chen Liang,Wu Xiaochun,Fan Changfa,Xu Liming,Xie Liming
Benefited from their broad-spectrum antimicrobial property, silver nanoparticles (AgNPs) have been widely used in various daily life and medical products. Consequently, the bio-safety of AgNPs, especially long-term in vivo biological effects is of more and more importance. However, there are no correlated publications about AgNP carcinogenicity at present. Thus, in this study, we have investigated the potential carcinogenicity of polyvinylpyrrolidone (PVP)-coated AgNPs with an intermediate size (diameter ~ 42.5 nm). The C57- ras transgenic mouse model (CB6F1 Tg mice) harboring human c-Ha-ras gene was used to shorten the duration of in vivo experiments from 2 years to 22 weeks. CB6F1 Tg mice were intravenously injected by different single doses of AgNPs (0.4, 4, and 20 mg/kg body weight) during the 22-week carcinogenicity study. There were no obvious AgNP-related neoplastic lesions by microscope examination and no increase in the incidence of non-neoplastic lesions in the AgNP-treated mice in our study. Overall, these results indicate that AgNPs (≤ 20 mg/kg) do not cause carcinogenesis in CB6F1 Tg mice via a single-dose intravenous injection. This provides useful toxicological information and is of great importance to more applications of AgNPs in the future.
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BMC Ophthalmology
·
2020
·Vol. 20
·期 1
·1-10
·
IF 1.413
Yan Weiming,Long Pan,Wei Dongyu,Yan Weihua,Zheng Xiangrong,Chen Guocang,Wang Jiancong,Zhang Zuoming,Chen Tao,Chen Meizhu
Background Retinitis pigmentosa (RP) is a kind of inherited retinal degenerative diseases characterized by the progressive loss of photoreceptors. RP has been a conundrum without satisfactory countermeasures in clinic until now. Acetaldehyde dehydrogenase 2 (ALDH2), a major enzyme involved in aldehyde detoxification, has been demonstrated to be beneficial for a growing number of human diseases, such as cardiovascular dysfunction, diabetes mellitus and neurodegeneration. However, its protective effect against RP remains unknown. Our study explored the impact of ALDH2 on retinal function and structure in N-methyl-N-nitrosourea (MNU)-induced RP rats.Methods Rats were gavaged with 5 mg/kg Alda-1, an ALDH2 agonist, 5 days before and 3 days after MNU administration. Assessments of retinal function and morphology as well as measurement of specific proteins expression level were conducted.Results Electroretinogram recordings showed that Alda-1 administration alleviated the decrease in amplitude caused by MNU, rendering protection of retinal function. Mitigation of photoreceptor degeneration in MNU-treated retinas was observed by optical coherence tomography and retinal histological examination. In addition, Western blotting results revealed that ALDH2 protein expression level was upregulatedwith increased expression of SIRT1 protein after the Alda-1 intervention. Besides, endoplasmic reticulum stress (ERS) was reduced according to the significant downregulation of GRP78 protein, while apoptosis was ameliorated as shown by the decreased expression of PARP1 protein.Conclusion sTogether, our data demonstrated that ALDH2 could provide preservation of retinal function and morphology against MNU-induced RP, with the underlying mechanism at least partly related to the modulation of SIRT1, ERS and apoptosis.
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ENVIRONMENTAL POLLUTION
·
2017
·
IF 5.099
Man Ren,Hao Zeng,Ping-An Peng,Hui-Ru Li,Cai-Ming Tang,Jian-Fang Hu
Polybrominated dibenzo- p -dioxins (PBDDs) and hydroxylated polybrominated diphenyl ethers (OH-PBDEs) can be formed from bromophenols (BPs) by thermal degradation , biosynthesis or phototransformation. However, it is unknown whether PBDDs and OH-PBDEs can be formed during the chemical production processes that utilize BPs as raw materials. 2,4,6-tribromophenol (2,4,6-TBP) is an important raw material for the synthesis of 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), a novel brominated flame retardant . In this study, PBDDs, polybrominated dibenzofurans (PBDFs) and OH-PBDEs have been identified and quantified in commercially available BTBPE and 2,4,6-TBP. Furthermore, their formation as unintentional by-products during the laboratory synthesis of BTBPE from 2,4,6-TBP and 1,2-dibromoethane in the presence of sodium carbonate has also been investigated. 2,3,7,8-substituted PBDDs and PBDFs (2,3,7,8-PBDD/Fs) were undetectable in commercial samples of BTBPE and present in low levels (nanogram per gram) in 2,4,6-TBP. Two tetrabrominated dibenzo- p -dioxins (TeBDDs), namely 1,3,6,8- and 1,3,7,9-TeBDD, and three hydroxylated pentabrominated diphenyl ethers (OH-pentaBDEs), namely 4′-OH-BDE121, 2′-OH-BDE121, and 6′-OH-BDE100, were identified or tentatively identified, and quantitatively estimated to be at concentrations in the range of undetectable to several thousands of nanograms per gram in commercial BTBPE and 2,4,6-TBP. TeBDDs and OH-pentaBDEs were formed as by-products from 2,4,6-TBP during BTBPE synthesis. Further studies need to be conducted in order to determine whether PBDD/Fs and OH-PBDEs are also formed during the industrial synthesis of other chemical compounds that utilize BPs as raw materials or intermediates.
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ADVANCED MATERIALS
·
2024
·
IF 27.4
Kangkang Liu,Lining Wang,Jing Peng,Yuanji Lyu,Yiming Li,Dengyi Duan,Wenyi Zhang,Guojiang Wei,Taipeng Li,Yuanjie Niu,Yang Zhao
Intravesical Bacillus Calmette–Guérin (BCG) is a well-established strategy for managing high-risk nonmuscle-invasive bladder cancer (NMIBC); however, over half of patients still experience disease recurrence or progression. Although the combined intravesical instillation of various chemotherapeutic drugs is implemented in clinical trials to enhance the BCG therapy, the outcome is far from satisfying due to severe irritative effects and treatment intolerance at high doses. Therefore, it is adopted the “biotin–streptavidin strategy” to doxorubicin (DOX)-encapsulated nanoparticles within live BCG bacteria (DOX@BCG) to improve treatment outcomes. Adherence of BCG to the bladder epithelium helps precisely target DOX@BCG to the local tumor cells and simultaneously increases intratumoral transport of therapeutic drugs. DOX@BCG effectively inhibits cancer progression and prolongs the survival of rats/mice with orthotopic bladder cancer owing to synergism between BCG-immunotherapy, DOX-chemotherapy, and DOX-induced immunogenic tumor cell death; furthermore, it exhibits improved tolerance and biosafety, and establishes antitumor immunity in the tumor microenvironment. Therefore, the drug-loaded live BCG bacterial delivery system holds considerable potential for clinical translation in the intravesical treatment of bladder cancer.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Enjuan Shi,Xiaoqin Wang,Huili Jing,Yayuan Xu,Lei Feng,Fatao He,Dajing Li,Zhuqing Dai
In this study, N -Methyl-N-nitrosourea (MNU) was intraperitoneally injected to construct a mouse retinitis pigmentosa (RP) model to evaluate the protective effect of chitosan and β-carotene on RP. The results demonstrated that chitosan synergized with β-carotene significantly reduced retinal histopathological structural damage in RP mice. The co-treatment group of β-carotene and chitosan restored the retinal thickness and outer nuclear layer thickness better than the group treated with the two alone, and the thickness reached the normal level. The content of β-carotene and retinoids in the liver of chitosan and β-carotene co-treated group increased by 46.75 % and 20.69 %, respectively, compared to the β-carotene group. Chitosan and β-carotene supplement suppressed the expressions of Bax, Calpain2, Caspase3, NF-κB, TNF-α, IL-6, and IL-1β, and promoted the up-regulation of Bcl2. Chitosan and β-carotene interventions remarkably contributed to the content of SCFAs and enhanced the abundance of Ruminococcaceae , Rikenellaceae , Odoribacteraceae and Helicobacteraceae . Correlation analysis demonstrated a strong association between gut microbiota and improvement in retinitis pigmentosa. This study will provide a reference for the study of the gut-eye axis.
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