JOURNAL OF MOLECULAR HISTOLOGY
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2025
·Vol. 56
·期 2
·1-11
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IF 2.2
Zhang Xiuping,Wang Shimin,Liang Lixia,Hu Fen,Zhang Xueluo,Cui Xiangrong,Zhang Zhiping,Wu Xueqing
Recurrent spontaneous abortion (RSA) brings tremendous difficulties to clinical treatment and prognosis. Pre-B-cell leukemia homeobox 1 (PBX1), as a functional transcription factor, involves in the regulation of cell apoptosis and proliferation. However, the underlying mechanism of PBX1 in RSA treatment has not been explored. We established a lipopolysaccharide (LPS)-induced abortion model and detected PBX1 expression with real-time PCR, western blot and immunohistochemistry. The PBX1-overexpressed adenovirus (AV-oePBX1) was infected into trophoblast cells treated with LPS to define the function of PBX1 on cell apoptosis, inflammation and NF-κB pathway. A luciferase reporter assay was conducted to validate the transcription regulation of PBX1 on transmembrane and ubiquitin like domain containing 1 (TMUB1). Compared to women with normal abortion, PBX1 was downregulated in the placental villous tissues of RSA patients. The placental tissues of LPS-treated mice also manifested notably reduction of PBX1 at mRNA and protein levels. PBX1 overexpression alleviated inflammation and apoptosis of trophoblast cells. Substantially, PBX1 was negatively correlated with TMUB1, which was highly expressed in RSA patients and LPS-treated mice. Moreover, PBX1 bound to TMUB1 promoter and inhibited its transcription. Interestingly, exogenous TMUB1 abolished the effects of PBX1 on apoptosis, inflammation, and NF-κB signal pathway. In total, PBX1 attenuated cell apoptosis and inflammation, and suppressed NF‐κB signal pathway induced by LPS through downregulating TMUB1 transcription. Therefore, PBX1 may be developed as a novel target for clinical treatment of RSA.
研究领域:
妇产科学
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分子生物学
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转化医学
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DOI
PubMed
高影响因子
Nanoscale
·
2024
·Vol. 16
·期 8
·4095-4104
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IF 5.8
Xinyi Cai,Tiantian Xu,Rui Ding,Dou Zhang,Guiquan Chen,Wenchang Zhao,Jiajie Hou,Hong Pan,Qian Zhang,Ting Yin
In recent years, tumor catalytic therapy based on nanozymes has attracted widespread attention. However, its application is limited by the tumor hypoxic microenvironment (TME). In this study, we developed oxygen-supplying magnetic bead nanozymes that integrate hemoglobin and encapsulate the photosensitizer curcumin, demonstrating reactive oxygen species (ROS)-induced synergistic breast cancer therapy. Fe3O4 magnetic bead-mediated catalytic dynamic therapy (CDT) generates hydroxyl radicals (˙OH) through the Fenton reaction in the tumor microenvironment. The Hb-encapsulated Fe3O4 magnetic beads can be co-loaded with the photosensitizer/chemotherapeutic agent curcumin (cur), resulting in Fe3O4-Hb@cur. Under hypoxic conditions, oxygen molecules are released from Fe3O4-Hb@cur to overcome the TME hypoxia, resulting in comprehensive effects favoring anti-tumor responses. Upon near-infrared (NIR) irradiation, Fe3O4-Hb@cur activates the surrounding molecular oxygen to generate a certain amount of singlet oxygen (1O2), which is utilized for photodynamic therapy (PDT) in cancer treatment. Meanwhile, we validated that the O2 carried by Hb significantly enhances the intracellular ROS level, intensifying the catalytic therapy mediated by Fe3O4 magnetic beads and inflicting lethal damage to cancer cells, effectively inhibiting tumor growth. Therefore, significant in vivo synergistic therapeutic effects can be achieved through catalytic–photodynamic combination therapy.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Bin Hu,Gongwen Du
Osteoarthritis (OA) is an age-related joint disease characterized by progressive heterogeneous changes in articular cartilage and subchondral bone. Osteoclast stimulating factor 1 (OSTF1) is a small intracellular protein involved in bone formation and bone resorption. However, to our best knowledge, its role in OA is still unclear. In this study, an OA rat model was established by anterior cruciate ligament transection (ALCT). OSTF1 was increased in the cartilage tissues of OA patients and OA rats. Next, the role of OSTF1 in interleukin-1β (IL-1β)-induced chondrocyte apoptosis, inflammation and extracellular matrix degradation was explored through loss of function assays. Strikingly, OSTF1 knockdown relieved IL-1β-induced chondrocyte apoptosis, with decreased cleaved caspase-3 and cleaved PARP levels. Besides, OSTF1 knockdown restrained IL-1β-induced inflammation and degradation of extracellular matrix of chondrocytes. Subsequently, the molecular mechanism of OSTF1 was explored. Transcriptomic analysis revealed the potential gene network map regulated by OSTF1 knockdown. Some differentially expressed genes (DEGs) were involved in regulating the NF-κB signaling pathway. Furthermore, our results demonstrated that OSTF1 knockdown inhibited IL-1β-activated the NF-κB signaling pathway. Ultimately, we analyzed the potential gene network map regulated by OSTF1 and its downstream NF-κB. Bioinformatics analysis showed that 18 DEGs in OSTF1-silenced chondrocytes overlapped with the NF-κB downstream targets. Collectively, our findings indicate that OSTF1 knockdown mitigates IL-1β-induced chondrocyte injury via inhibiting the NF-κB signaling pathway.
研究领域:
医学
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分子生物学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Cong Dai,Ying Xu,Bo Liu,Biao Gu
Organic cages with long-wavelength emission and ratiometric signal are pivotal but still challenging for their sensing application. Probes often suffer from single signal and poor water solubility, which are detrimental to hypochlorous acid (HClO) sensing in aqueous solution. Here, we report the fabrication of organic cages with long-wavelength dual emission for ratiometric fluorescent sensing of HClO. The nanosized organic cages (OCs-1 and OCs-2, derived from the reaction of 1,3,5-tris(aminomethyl)benzene) and 2- or 4-hydroxyisophthalaldehyde) showed robust stability across varying pH. Both OCs-1 and OCs-2 exhibited pH-responsive dual emission attributed to hydroxy-1,3-diiminobenzene group, facilitated by the enol-keto tautomerism and constrained molecular motion within the capsule topological structure. Owing to the redox reaction between imine bond of OCs-2 and HClO, the dismantling of cage-like structure led to significant quenching of emission at 620 nm and enhancement of emission at 500 nm. Based on the ratiometric signal of OCs-2, a highly effective sensing method for HClO was established. The proposed method gave the linearity range of 0.5–3 μM, the limit of detection (3 s ) of 4 nM, and remarkable precision with the relative standard deviation of 0.58 % for 10 replicate determinations of 1.5 μM HClO. The recoveries of spiked HClO in domestic water and disinfectant samples ranged from 94.09 % to 104.24 %.
研究领域:
分析化学
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生物医学工程
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材料科学
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DOI
高影响因子
Nano Today
·
2024
·
IF 13.2
Yaqiao Li,Lingxiao Li,Yanzhong Hao,Jingxuan Zhang,Cuiyun Liu,Erwei Zhao,XianBao Shi,Xiaohui Pu,Jin Sun,Zhonggui He,Bingjun Sun
Dimeric prodrug self-assembly nanoparticles (DPS NPs) present promising avenues for chemotherapeutic delivery, yet optimizing the linker design for effective SN38 delivery remains challenging. We developed various SN38 dimeric prodrugs with differing linker lengths to explore how linker length impacts DPS NP performance. Our study reveals that linker length critically affects the nanoparticles assembly stability and activation efficiency. Specifically, too short linkers compromise assembly stability and lead to premature drug activation in the bloodstream, raising safety concerns. Conversely, too long linkers hinder both assembly stability and activation efficiency within tumor cells, diminishing anti-tumor effectiveness. The optimal linker (C12) achieved the best balance, ensuring robust assembly stability and high activation efficiency, thereby enhancing anti-tumor efficacy while maintaining a favorable safety profile. This work underscores the significance of linker length in designing effective DPS NPs for cancer treatment.
研究领域:
药物化学
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纳米医学
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肿瘤学
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产品关联
DOI
高影响因子
CANCER IMMUNOLOGY IMMUNOTHERAPY
·
2025
·Vol. 74
·期 3
·1-17
·
IF 5.1
Han Tianci,Guo Xiaoqi,Xie Junwei,Tong Wei,Zhang Liang
Objective Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a high metastasis rate and a poor prognosis. ETS variant transcription factor 1 (ETV1) plays an important role in multiple malignancies. However, its function in ESCC progression and tumor microenvironment (TME) remains to be explored. In this study, we characterized the role of ETV1 in ESCC process and TME. Methods Gene expression and immune infiltration in ESCC samples from the Cancer Genome Atlas (TCGA) were analyzed. The expression of ETV1 in clinical samples was detected by real-time PCR, western blot and immunohistochemistry staining. Cell growth was detected by CCK-8 and colony formation assays. Macrophage phenotypes were determined using flow cytometry. Immunofluorescence double staining was used to detect the tumor-associated macrophage (TAM) infiltration. The tumor volume was recorded and weighed. Transcriptional activity was measured using dual-luciferase assay, chromatin immunoprecipitation (ChIP) assay and DNA pull-down assay. Results In this study, through analysis of ESCC samples from TCGA database and the clinic, we noticed that ETV1 was highly expressed in ESCC tumor tissues and was associated with TAM infiltration. Overexpression of ETV1 promoted ESCC cell proliferation in vitro and xenograft tumor growth in nude mice, while ETV1 knockdown elicited the opposite effects. Furthermore, ETV1 upregulation in tumor tissues was found to drive M2 macrophage infiltration both in vitro (transwell assays) and in vivo (xenograft tumor models). C–C motif chemokine ligand 2 (CCL2), a key factor inducing M2 macrophage polarization, was also found to be elevated in ESCC tumor tissues. Mechanism study demonstrated that ETV1 facilitated M2 macrophage infiltration via the transcriptional modulation of CCL2. In addition, the cause of the changes in ETV1 activity and expression was investigated. The E2 small ubiquitin-like modifier (SUMO) binding enzyme UBC9 increased ETV1 activity and expression, indicating the presence of SUMO modification in ETV1. Conclusions Our data deciphered the mechanism of ETV1-mediated M2 macrophage infiltration in the TME of ESCC, which has important implications for the development of novel prognostic and therapeutic targets to optimize current therapies against ESCC.
研究领域:
肿瘤学
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免疫学
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转录调控
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Huijiao Fu,Xiaoqiao Guo,Feng Fang,Cao Zhou,Yuanyuan Chen,Xuanbo Zhang,Bingchen Zhang,Xinran Li,Qiwen Liu,Jie Liu,Wei Chen,Ling Yu,Zhiqiang Yu,Xuefeng Wang
Cisplatin serves as the cornerstone medication in ovarian cancer (OC) chemotherapy; however, numerous resistance factors exist, resulting in unsatisfactory clinical treatment outcomes. Concurrently, OC frequently establishes an immunosuppressive microenvironment, which further exacerbates the challenges of cisplatin chemotherapy. Hence, it is particularly significant to explore a therapeutic approach capable of overcoming cisplatin resistance while reversing the immunosuppressive microenvironment of OC. Here, we synthesized a novel cisplatin polyprodrug (PTP) containing thioketal units, which self-assembled with a stimulator of interferon genes (STING) small-molecule agonist (SR-717) to form redox-smart-responsive PTP@SR-717 nanoparticles (NPs), enabling synergistic chemo-immunotherapy. Specifically, PTP@SR-717 NPs enhanced the anti-tumor effect of cisplatin through three key mechanisms: (i) Pre-target factors: Enhancing intracellular cisplatin uptake and reducing GSH-mediated detoxification to promote platinum accumulation. (ii) On-target factors: Utilizing molecular damage-associated molecular patterns (DAMPs) triggered by cisplatin to activate the STING pathway, thereby synergistically amplifying the STING-TBK1-IRF3 signaling and efficiently triggering an immune response. (iii) Post-target factors: Combining chemotherapy and immunotherapy to harness the immune system for tumor eradication. In conclusion, this study presents an effective approach to addressing the challenges associated with cisplatin in the clinical treatment of OC.
研究领域:
肿瘤学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 12
·1-16
·
IF 8.1
Hou Rui,Sun Xinrui,Cao Shiyao,Wang Yadong,Jiang Luo
The metabolic reprogramming in high-grade serous ovarian carcinoma (HGSOC) affects the tumor stemness, which mediates tumor recurrence and progression. Knowledge of the stemness and metabolic characteristics of HGSOC is insufficient. Squalene epoxidase (SQLE), a key enzyme in cholesterol metabolism, was significantly upregulated in HGSOC samples with a fold change of about 4 in the RNA sequencing analysis. SQLE was positively related to peritoneal metastasis and poor prognosis of HGSOC patients. Functionally, SQLE drove cancer cell proliferation and inhibited apoptosis to accelerate HGSOC growth. SQLE was highly expressed in ALDH + CD133 + FACS-sorted cells derived from HGSOC cells and ovarian cancer stem cells (OCSCs)-enriched tumorspheres. SQLE overexpression resulted in enhanced CSC-like properties, including increased tumorsphere formation and stemness markers expression. In vivo, SQLE not only promoted cell line-derived xenografts growth but extended the OCSCs subpopulation of single-cell suspension. Moreover, non-targeted metabolomics profiling from UPLC-MS/MS system identified 90 differential metabolites responding to SQLE overexpression in HGSOC cells. Among them, the dysfunctional metabolisms of cholesterol and glutathione were involved in the maintenance of HGSOC stemness. Previous studies showed the alteration of N6-Methyladenosine (m6A) modification in HGSOC development. Herein, the m6A modification in the 3’UTR and CDS regions of SQLE mRNA was increased due to upregulated methyltransferases WTAP and downregulated demethylases FTO, which was recognized by m6A-binding proteins IGF2BP3, rather than IGF2BP1 or IGF2BP2, thereby stabilizing the SQLE mRNA. These results suggested that SQLE was a novel potential clinical marker for predicting the HGSOC development and prognosis, as well as a potential therapeutic target of HGSOC.
研究领域:
肿瘤学
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分子生物学
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代谢组学
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癌症生物学
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表观遗传学
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产品关联
DOI
PubMed
高影响因子
BMC Cardiovascular Disorders
·
2024
·Vol. 24
·期 1
·1-13
·
IF 2
Wang Xin,Sun Limin
MI (myocardial infarction) often triggers severe heart failure and is one of the leading causes of death worldwide. Receptor expression-enhancing protein 5 (REEP5), a member of REEPs, acts as regulators of endoplasmic reticulum (ER) affecting cardiac functions. Based on GSE114695 profile data, REEP5 was decreased in the left ventricle of MI mice. However, its role and potential mechanism in MI remain to be investigated. In the present study, the mouse MI model was established by ligation of the left anterior descending artery. REEP5 expression was downregulated in the infarct penumbra area of MI mice. Next, its role during MI was explored by gain-of-function. Interestingly, REEP5 overexpression improved left ventricular function of mice with MI, accompanied with reduced infarct size. In cardiomyocytes, REEP5 overexpression inhibited ER stress, accompanied with repressive phosphorylation of PERK and IRE1α, and the decreased nuclear translocation of ATF6. Subsequently, REEP5 overexpression downregulated the levels of Chop and cleaved caspase-12, further alleviating ER stress-induced apoptosis, which was consistent with the in vivo results. Moreover, REEP5 was found to bind to C-type lectin member 5 A (CLEC5A), a protein that triggers cardiac dysfunction. CLEC5A, whose expression was elevated in hypoxia-induced cell models, led to cardiomyocyte apoptosis. Noteworthily, REEP5 overexpression markedly abolished the effects of CLEC5A on ER stress-induced apoptosis. Taken together, REEP5 mediated the function of CLEC5A to relieve MI via inhibiting ER stress-induced apoptosis in vivo and in vitro. REEP5 may be a promising target for treating MI.
研究领域:
心脏病学
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分子生物学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
·
2024
·
IF 3.4
Wenjia Tong,Conglei Song,Danqun Jin,Min Li,Zimei Cheng,Guoping Lu,Bin Yang,Fang Deng
Sepsis is a systemic inflammatory response caused by an infection, which can easily lead to acute lung injury. Quiescin Q6 sulfhydryl oxidase 1 (QSOX1) is a sulfhydryl oxidase involved in oxidative stress and the inflammatory response. However, there are few reports on the role of QSOX1 in sepsis-induced acute lung injury (SALI). In this study, mice model of SALI was constructed by intraperitoneal injection with lipopolysaccharide (LPS). The increased inflammatory response and lactate dehydrogenase activity in bronchoalveolar lavage fluid (BALF) indicated successful modeling. Increased QSOX1 expression was both observed in lung tissues and lung macrophages of sepsis mice accompanied by increased polarization of M1-type macrophages. To explore the role of QSOX1 in the SALI, lentivirus containing QSOX1-specific overexpression or knockdown vectors were used to change QSOX1 expression in LPS-treated RAW264.7 cells. QSOX1 suppressed LPS-induced M1 polarization and further inhibited inflammatory response in RAW264.7 cells. Interestingly, the phosphorylation of epidermal growth factor receptor (EGFR), the promoter of M1 polarization in macrophages, was found to be downregulated upon QSOX1 overexpression in RAW264.7 cells. Mechanically, the binding of QSOX1 to EGFR protein promoted EGFR ubiquitination and degradation, thereby down-regulating EGFR phosphorylation. Moreover, inhibiting EGFR expression or its phosphorylation restored the impact of QSOX1 silencing on M1 polarization and inflammation in the LPS-treated RAW264.7 cells. In summary, QSOX1 may exert anti-inflammatory effects in SALI by inhibiting EGFR phosphorylation-mediated M1 macrophage polarization. This presented a potential target for the treatment and prevention of SALI.
研究领域:
免疫学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Genes & Genomics
·
2024
·
IF 1.6
Lv Junqi,Ma Shengmao,Wang Xiaowen,Dang Jifang,Ma Fuchun
Background Non-small cell lung cancer (NSCLC) contributes to the vast majority of cancer-related deaths. Proteasome 26S subunit, non-ATPase 12 (PSMD12), a subunit of 26S proteasome complex, is known to play the tumor-promoting role in several types of cancer but its function in NSCLC remains elusive. Objective To explore the role and underlying mechanisms of PSMD12 in NSCLC. Methods The PSMD12 expression in human normal lung epithelial cell line (BEAS-2B) and four NSCLC cell lines (A549, NCI-H1299, NCI-H1975, Calu-1) were determined by qRT-PCR and western blot. Malignant phenotypes of NSCLC cells were detected by CCK-8, EdU staining, immunofluorescence staining for E-cadherin, flow cytometry, and Transwell assays to assess cell viability, proliferation, epithelial-mesenchymal transition (EMT), apoptosis, migration and invasion. Dual luciferase assay was used to verify the regulatory role of transcription factor on the promoter. Results We identified the upregulation of PSMD12 in NSCLC tissues based on the GEO datasets, which further verified in NSCLC and BEAS-2B cell lines. PSMD12 knockdown significantly suppressed malignant behaviors of NSCLC cells, including cell growth, invasion, and migration, while PSMD12 overexpression presented the opposite effects. Interestingly, we found that PSMD12 upregulated the tumor-promoting factor TrxR1 mRNA expression. For its potential mechanisms, we demonstrated that PSMD12 elevated transcription factor Nrf2 protein level and promoted Nrf2 nuclear translocation. And Nrf2 further increased TrxR1 promoter activity and enhanced TrxR1 transcription. Meanwhile, we proved that TrxR1 overexpression erased the inhibitory effect of PSMD12 knockdown. Conclusion PSMD12 promotes NSCLC progression by activating the Nrf2/TrxR1 pathway, providing a novel prognostic and therapeutic target for NSCLC treatment.
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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癌症研究
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产品关联
DOI
PubMed
高影响因子
NEUROPEPTIDES
·
2025
·
IF 2.7
Qiankun Quan,Xinxin Ma,JianJun Feng,Wanni Li,Xi Li
Alzheimer's disease (AD) is a neurodegeneration driven by beta-amyloid (Aβ) deposits in the brain involving autophagy dysfunction. Ginsenoside Rg1, a pharmacologically active compound found in ginseng, has possible therapeutic effects for AD. This study discovered that FGR proto-oncogene (FGR) was a therapeutic target of Rg1 in AD and it was possibly involved in autophagy. C57BL/6 J mice were injected with 5 μL (1 μg/mL) Aβ 1–42 in the right lateral ventricle to establish an AD model. AD mouse hippocampus had high FGR expression. Intragastrically administered Rg1 (40 mg/kg) decreased FGR protein levels in AD mice's hippocampus and improved memory function in AD mice. Both sides of the mice hippocampal fissure were administered with 2 μL lentiviral particles (1 × 10 7 TU) containing FGR overexpression plasmids. FGR overexpression rendered Rg1 ineffectual in restoring memory function and reducing hippocampal neuron damage. We injected 2 μL lentiviral particles (1 × 10 7 TU/mL) containing short hairpin RNA plasmids targeting FGR to the mice hippocampal fissures. FGR knockdown improved spatial memory function of AD mice, reduced hippocampal neuron apoptosis, and prevented Aβ accumulation. HT22 cells were transfected with small interfering RNA targeting FGR. FGR knockdown increased the viability of Aβ 1–42 treated HT22 cells. BACE1 and LC3II/I protein levels were decreased and p62 and SIRT1 were increased in AD mice and cells with FGR knockdown. LC3 was down-regulated after inhibiting FGR expression in Aβ 1–42 treated hippocampal neurons. In conclusion, Rg1 exerts anti-AD functions by targeting FGR and downregulating its expression.
研究领域:
神经生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
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