Bioactive Materials
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2024
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IF 18
Zilin Tan,Liangjie Tian,Yang Luo,Kexin Ai,Xuehua Zhang,Haitao Yuan,Jinfan Zhou,Guangyao Ye,Shuofei Yang,Ming Zhong,Gaohua Li,Yanan Wang
Colorectal cancer (CRC) recurrence post-surgery remains a major challenge. While Chimeric Antigen Receptor (CAR)-engineered natural killer (NK) cells hold immense therapeutic potential, their intratumoral infiltration ability remains limited, hampering efficacy. Building upon prior research suggesting that chemokines like C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) recruit CAR-NK cells, we hypothesized that tumor cell m6A methylation, regulated by Methyltransferase-like 3 (METTL3), influences chemokine secretion. This study aims to elucidate the underlying mechanisms and improve METTL3 inhibition efficiency. We designed an adhesive hemostasis hydrogel loaded with STM2457, a METTL3 inhibitor, aimed at sustained release in the acidic tumor microenvironment. In vitro, the hydrogel promoted CAR-NK cell recruitment and tumor killing via sustained METTL3 inhibition. The hydrogel's Schiff base bonds further enabled intestinal adhesion and hemostasis in an incomplete tumor resection model of CRC. Combining the hydrogel with CAR-NK cell therapy significantly reduced CRC recurrence in vivo. Overall, our study reveals the crucial role of METTL3 in CRC recurrence and proposes a promising, multimodal strategy using STM2457-loaded hydrogel and CAR-NK cells for enhanced therapeutic efficacy.
研究领域:
肿瘤学
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分子生物学
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免疫疗法
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生物医学工程
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DOI
PubMed
高影响因子
Scientific Reports
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2024
·Vol. 14
·期 1
·1-16
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IF 3.8
Liu Lu,Zhao Xuefen
The development of intelligent, environmentally responsive and biocompatible photothermal system holds significant importance for the photothermal combined therapy of tumors. In this study, inspired by Lactobacillus (LAC), we prepared a biomimetic nanoplatform PDA&DOX@LAC for tumor photothermal-chemotherapy by integrating the chemotherapeutic drug doxorubicin (DOX) with dopamine through oxidative polymerization to form polydopamine (PDA) on the surface of LAC. The PDA&DOX@LAC nanoplatform not only achieves precise and controlled release of DOX based on the slightly acidic microenvironment of tumor tissues, but also exhibits enzyme-like properties to alleviate tumor hypoxia. Under near-infrared light irradiation, it effectively induces photothermal ablation of tumor cells, enhances cellular uptake of DOX with increasing temperature, and thus efficiently inhibits tumor cell growth. Moreover, it is further confirmed in vivo experiments that photothermal therapy combined with PDA&DOX@LAC induces tumor cells apoptosis, releases tumor-associated antigens, which is engulfed by dendritic cells to activate cytotoxic T lymphocytes, thereby effectively suppressing tumor growth and prolonging the survival period of 4T1 tumor-bearing mice. Therefore, the PDA&DOX@LAC nanoplatform holds immense potential in precise tumor targeting as well as photothermal combined therapy and provides valuable insights and theoretical foundations for the development of novel tumor treatment strategies based on endogenous substances within the body.
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
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2025
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IF 5.4
Yang Yu,Lixin Fan,Chunling Gao,Yang Ping,Liting Mu,Weitong Sun
Despite the advances made in cancer treatment, malignant tumors remain a significant threat to human health. Tumor multidrug resistance (MDR) constitutes a significant impediment to the effectiveness of chemotherapy. Thus, the reversal of MDR has become a critical research domain for medical professionals. Now, paclitaxel (PTX) is encapsulated in a reduction-sensitive polymer pre-drug micelle called mPEG-SS-IND(PSI), which reduces the MDR of PTX and enhances its anti-tumor efficacy. The PSI/PTX micelles show excellent reduction sensitivity and stability. In vitro , the harmful effect of PTX on MCF-7/PTX cells is enhanced by the PSI/PTX micelles, while its damaging effect on normal cells is decreased. Furthermore, compared to PTX solution, PTX encapsulated in PSI/PTX micelles exhibits reduced volume distribution and clearance, longer blood circulation time, and greater drug concentration area under the curve. Furthermore, in vivo studies using BALB/c subcutaneous tumor-bearing mice demonstrate decreased systemic toxicity and enhanced therapeutic effectiveness of PTX. This study proves that the potential utility of reduction-sensitive polymer pre-drug micelles as a delivery method for overcoming MDR for PTX and targeting tumors.
研究领域:
药理学
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肿瘤学
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药物递送系统
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癌症治疗
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DOI
高影响因子
Open Life Sciences
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2025
·Vol. 20
·期 1
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IF 1.7
Chengrong Huang,Hao Zhang,Jing Wang,Jianfei Li,Qian Liu,Qiyin Zong,Yunyun Zhang,Qin Wang,Qiang Zhou
A growing body of evidence has shown that hepatitis B surface antigen (HBsAg) mutations can influence the occurrence of occult hepatitis B infection (OBI), particularly amino acid substitutions in small hepatitis B surface proteins (SHBs). The mechanistic basis for these results, however, remains unclear. This study was designed to explore the potential impact and mechanisms of OBI-related SHBs mutations on serum HBsAg. Huh7 and HepG2 cells were transfected with plasmids encoding wild-type (WT) or OBI-related SHB mutation-containing sequences, after which a chemiluminescence approach was used to detect HBsAg levels in cell culture supernatants. Western blotting was further used to assess HBsAg and endoplasmic reticulum stress (ERS)-related protein levels in lysates prepared from these cells, while the localization of HBsAg within cells was assessed via immunofluorescent staining. Cells transfected with OBI-related SHB mutation-encoding plasmids exhibited lower supernatant HBsAg levels than cells transfected with WT plasmids. Intracellular and extracellular HBsAg levels in these mutant plasmid-transfected cells were lower relative to those for WT plasmid-transfected cells, and HBsAg accumulation within the ER was detected via immunofluorescent staining in cells transfected with OBI-related SHB mutation-encoding plasmids, ERS-related protein content was also significantly increased in mutant plasmid-transfected cells as compared to those in the WT group. These results suggest that proteins harboring OBI-related mutations may tend to accumulate in the ER, thereby triggering an ERS response and impairing the transcription and translation of HBsAg via the activation of the unfolded protein response and ER-associated protein degradation pathway. These effects ultimately reduce the overall assembly of HBV virions in the ER and their associated secretion.
研究领域:
病毒学
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分子生物学
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医学
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DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
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2025
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IF 4.2
Aiming Wang,Fan Zhang,Wenqiang Zhang,Jian Gong,Xiaohong Sun
Mitochondrial autophagy (mitophagy) plays an essential role in the maintenance of mitochondrial homeostasis. Defective mitophagy triggered by amyloid beta (Aβ) is linked to neuronal deterioration and neurodegeneration in Alzheimer's disease (AD). However, the molecular mechanism underlying the defective mitophagy in AD is still not fully illustrated. Protein phosphatase Mn 2+ /Mg 2+ -dependent 1D (PPM1D) triggers autophagy in mouse embryonic fibroblasts. Downregulated PPM1D in the hippocampus of APP/PS1 mice. This study aims to investigate the role of PPM1D in the progression of AD. Here, APP/PS1 mice were used to mimic AD, and rAAV2 vectors expressing PPM1D were injected into the bilateral hippocampus. In vitro , the mouse hippocampal neuron cell line HT22 was stimulated by Aβ 1–42 to trigger neuronal damage. High PPM1D expression alleviated the impairments of spatial cognition and memory in APP/PS1 mice. Additionally, PPM1D enhanced autophagosome formation, lysosomal degradation of impaired mitochondria, amyloid plaque deposition, and neuronal degeneration and apoptosis in the hippocampus of APP/PS1 mice. Similar effects of PPM1D on neuronal apoptosis and mitophagy were observed in Aβ 1–42 -treated HT22 cells, and the effects could be reversed by the mitophagy inhibitor cyclosporine A. In conclusion, PPM1D facilitates mitophagy to inhibit the progression of AD-like disease. Taken together, the present work uncovers defective mitophagy in AD may be associated with down-regulated PPM1D, and PPM1D may be a potential therapeutic target for AD treatment.
研究领域:
神经科学
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分子生物学
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医学
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DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
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2024
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IF 2.2
Dan LI,Le WANG,Shufeng SHI,Xiaofeng DENG,Xuehan ZENG,Yunong LI,Shulin LI,Peng BAI
Acupuncture has obvious therapeutic effect on intracerebral hemorrhage (ICH). miR-34a-5p regulated by acupuncture was found to attenuate neurological deficits in ICH. However, the underlying mechanisms are unclear. Ubiquitin Like 4A (UBL4A) has not been studied in ICH. SD rats were injected with autologous blood to induce ICH and treated with Baihui-penetrating-Qubin acupuncture. Acupuncture resulted in an increase in forelimb placing test scores, and a decrease in corner test scores and brain water content of ICH rats. Histopathological examination showed that acupuncture inhibited ICH-induced inflammation, decreased damaged neurons and increased UBL4A expression. UBL4A overexpression increased cell viability, inhibited apoptosis, reduced ROS level and increased MnSOD activity, mitochondrial membrane potential and mtDNA level in rat embryonic primary cortical neurons. miR-34a-5p knockdown increased UBL4A expression, apoptosis rate and ROS level in hemin-treated neurons. Dual luciferase assays showed that miR-34a-5p bound to UBL4A. Apoptotic cells and ROS level were increased in hemin-treated neurons with UBL4A and miR-34a-5p knockdown. We firstly demonstrate the inhibitory effect of UBL4A on neuronal apoptosis, and the regulation relationship between UBL4A and miR-34a-5p. This study provides a new candidate target for ICH treatment and more basis for elucidating the molecular mechanism of acupuncture. In the future, we will conduct a deeper exploration of the effects of UBL4A on ICH.
研究领域:
神经科学
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分子生物学
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针灸
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神经病学
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DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2025
·Vol. 31
·期 1
·1-20
·
IF 6.4
Gao Bai,Jing Yuchen,Li Xi,Cong Shuyan
Background Mitochondrial dysfunction and neuronal damage are major sign of cytopathology in Huntington’s disease (HD), a neurodegenerative disease. Ubiquitin specific peptidase 11 (USP11) is a deubiquitinating enzyme involved in various physiological processes through regulating protein degradation. However, its specific role in HD is unclear.Methods To interfere with USP11 expression, adeno-associated viruses 2 containing USP11-specific shRNA were injected into the bilateral striatum of 12-week-old R6/1 and WT mice. In vitro, the inducible PC12 cell model of HD was used in which the expression of an N-terminal truncation of huntingtin, with either wild type (Q23) or expanded polyglutamine (Q74) can be induced by the doxycycline. USP11 was knocked down to study its role in HD. The protein expression patterns in Q74 cells were quantified by label-free proteomics to further explore the target protein of USP11. Detecting the association between USP11 and Phosphatase and Tensin Homolog (PTEN) through Co-IP.Results Herein, USP11 was found to be upregulated in the striatum of R6/1 mice (an HD model with gradual development of symptoms) in an age-dependent manner. The spontaneous HD was alleviated by silencing USP11, as evidenced by improved locomotor activity and spatial memory, attenuated striatal atrophy in R6/1 mice, reduced accumulation of mutant huntingtin protein, and restored mitochondrial function in vitro and in vivo. The results of label-free proteomics revealed a significant change in the protein expression profile. Through functional enrichment, we focused on PTEN, known as a negative regulator of the AKT pathway. We demonstrated that USP11 downregulation promoted ubiquitination modification of PTEN and activated the AKT pathway, and PTEN overexpression reversed the effects of USP11 knockdown.Conclusion sCollectively, USP11 knockdown protects R6/1 mouse neurons from oxidative stress by alleviating mitochondrial dysfunction, thereby preventing the HD progression. This is achieved by inhibiting PTEN expression, which in turn activates the AKT pathway. This study suggests that USP11-PTEN-AKT signaling pathway may be a new attractive therapeutic target for HD.
研究领域:
神经退行性疾病
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分子生物学
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神经科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
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IF 9.4
Yimin Gong,Hui Zhang,Mingzhu Lu,Jiayu Sun,Yu Jia,Yannan Yang,Xiaofeng Liu,Bo Yin,Yaming Zhou,Yun Ling
Studies on the function-integrated nanocomposites with well-tuned morphologies have received considerable interest. Here, we reported the preparation of mesoporous carbon nanobowl integrated with stoichiometric γ-Fe 2 O 3 and GdPO 4 nanoparticles (Fe-Gd/MCN-B) for morphological advantage exploration. Followed by (i) emulsion-induced interface anisotropic assembly of polydopamine, (ii) solvent evaporation-induced sorption of Wells-Dawson-like heterometallic cluster of {Fe 6 Gd 6 P 6 } and (iii) temperature-programmed carbonization, Fe-Gd/MCN-B with the size around 200 nm was isolated. Our in-vitro studies revealed that Fe-Gd/MCN-B showed a 63.0 % amplified photoacoustic (PA) signal intensity as compared with its nanospherical analogue of Fe-Gd/MCN-S owing to the enhanced light harvesting and photothermal conversion on the interface of its nanobowl morphology. Furthermore, the combined magnetic resonance (MR) imagining, drug delivery and photothermal treatment efficacy in Fe-Gd/MCN-B were also validated in-vitro. These results demonstrated that the delicate design of the morphology of function-integrated nanocomposites is an available way for enhanced imaging performance.
研究领域:
生物医学工程
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材料科学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
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IF 7.6
Abdullrahman M. Al-Bishari,Tingting Liu,Jiatong Zhuang,Qihong Zhang,Jiaquan Chen,Yan Wang,Chuanyang Liu,Peng Gao,Jinsong Liu,Lei Lu
Advancements in guided bone regeneration (GBR) rely on the development of membranes that can effectively control drug delivery and facilitate bone repair. This study introduces a triple-layered multi-functional membrane (MFM), with each layer serving a specific release profile and function. These layers consist of Qk peptide, strontium (Sr), and vancomycin (Van) for angiogenesis, bone growth, and infection control. The MFM was meticulously designed to ensure sustained drug release kinetics and improved bone regeneration. The membrane morphology was analyzed via SEM, and its mechanical properties were measured via stress–strain curves. In vitro studies confirmed the controlled release of the agents for 21 days. These findings indicate significant enhancements needed for GBR, as supported by in vitro results. The synergy of the membrane's components contributes to a greater therapeutic impact. Furthermore, in vivo results further supported the exceptional performance of MFM in GBR. Within 5 days of implantation, notable improvements in revascularization were observed. After 1 month, micro-CT scans displayed accelerated bone regeneration, while the membrane effectively prevented bacterial growth within 3 days. The MFM/Van-Sr-Qk membrane shows excellent potential for advancing bone regeneration and GBR therapies, warranting further research and development in this promising field.
研究领域:
生物医学工程
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材料科学
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组织工程
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药学
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骨科
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Subramani Kandhasamy,Baofang Wu,Jiayin Wang,Xiaojing Zhang,Gao Hongzhi,Da-Peng Yang,Yiming Zeng
Hydrogels incorporating natural biopolymer and adhesive substances have extensively been used to develop bioactive drugs and to design cells encapsulating sturdy structure for biomedical applications. However, the conjugation of the adhesive in most hydrogels is insufficient to maintain long-lasting biocompatibility inadequate to accelerate internal organ tissue repair in the essential native cellular microenvironment. The current work elaborates the synthesis of charged choline-catechol ionic liquid (BIL) adhesive and a hydrogel with an electronegative atom rich polyphenol (PU)-laden gelatinmethacryloyl (GelMA) to improve the structural bioactivities for in vivo tracheal repair by inducing swift crosslinking along with durable mechanical and tissue adhesive properties. It was observed that Bioactive BIL and PU exhibited potent antioxidant (IC 50 % of 7.91 μg/mL and 24.55 μg/mL) and antibacterial activity against E. coli , P. aeruginosa and S. aureus . The novel integration of photocurable GelMA-BIL-PU revealed outstanding mechanical strength, biodegradability and sustained drug release. The in vitro study showed exceptional cell migration and proliferation in HBECs, while in vivo investigation of the GelMA-BIL-PU hydrogel on a rat's tracheal model revealed remarkable tracheal reconstruction, concurrently reducing tissue inflammation. Furthermore, the optimized GelMA-BIL-PU injectable adhesive bioink blend demonstrated superior MSCs migration and proliferation, which could be a strong candidate for developing stem cell-rich biomaterials to address multiple organ defects.
研究领域:
生物医学工程
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组织工程
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干细胞生物学
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材料科学
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药剂学
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产品关联
DOI
PubMed
高影响因子
IMMUNOLOGICAL INVESTIGATIONS
·
2024
·
IF 2.9
Wei Zhang,Chengcheng Fan,Zhongxue Yi,Tao Du,Nana Wang,Weizhu Tian,Qian Pan,Xiande Ma,Zhe Wang
Background Cerebral ischemia/reperfusion injury (CIRI) is still a complicated disease with high fatality rates worldwide. Transmembrane Protein 79 (TMEM79) regulates inflammation and oxidative stress in some other diseases.Methods CIRI mouse model was established using C57BL/6J mice through middle cerebral artery occlusion-reperfusion (MCAO/R), and BV2 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) to simulate CIRI. Brain tissue or BV2 cells were transfected or injected with lentivirus-carried TMEM79 overexpression vector. The impact of TMEM79 on CIRI-triggered oxidative stress was ascertained by dihydroethidium (DHE) staining and examination of oxidative stress indicators. Regulation of TMEM79 in neuronal apoptosis and inflammation was determined using TUNEL staining and ELISA.Results TMEM79 overexpression mitigated neurological deficit induced by MCAO/R and decreased the extent of cerebral infarct. TMEM79 prevented neuronal death in brain tissue of MCAO/R mouse model and suppressed inflammatory response by reducing inflammatory cytokines levels. Moreover, TMEM79 significantly attenuated inflammation and oxidative stress caused by OGD/R in BV2 cells. TMEM79 facilitated the activation of Nrf2 and inhibited NLRP3 and caspase-1 expressions. Rescue experiments indicated that the Nrf2/NLRP3 signaling pathway mediated the mitigative effect of TMEM79 on CIRI in vivo and in vitro.Conclusion Overall, TMEM79 was confirmed to attenuate CIRI via regulating the Nrf2/NLRP3 signaling pathway.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2024
·
IF 3.8
Yan Li,Hui Song,Jia Xu,Yunping Wang,Lu Bai,Haixu Wang,Jianfang Zhang
This study aimed to elucidate the role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in polycystic ovary syndrome (PCOS). A rat model PCOS was constructed by subcutaneous injection with dehydroepiandrosterone (DHEA). Follicular atresia and reduced granular cells (GCs) in ovaries suggested successful modeling. The low expression of TIGAR was observed in ovarian tissue of PCOS rat. To explore the role of TIGAR in PCOS, lentivirus carrying the TIGAR were used to up-regulate TIGAR expression. TIGAR overexpression reduced the DHEA-induced increase of ovarian weight, the levels of estradiol (E2), and the ratio of luteinizing hormone/follicle-stimulating hormone (LH/FSH) in the serum, as well as improved the morphology of the follicle, especially increased the thickness of the GC layer, which attributed to the inhibition of apoptosis by TIGAR. In addition, high expression of TIGAR inhibited oxidative stress in ovaries of PCOS rat, as evidenced by decreased level of malondialdehyde (MDA), and reactive oxygen species (ROS), and enhanced activity of glutathione peroxidase (GPX) and superoxide dismutase (SOD). Mechanically, Nrf2/OH-1 signal pathway was activated by TIGAR. The effect of TIGAR on PCOS were verified in the primary rat GCs treated with dihydrotestosterone, but also the rescue experiment was performed. Downregulation of Nrf2 reversed the effects of TIGAR, indicating that TIGAR suppressed oxidative stress and GC apoptosis by activating Nrf2/OH-1 pathway in PCOS. Finally, non-targeted metabolomics revealed that TIGAR might affect the energy metabolic pathway, thereby altering the metabolic profile of primary rat GCs. This study provided new insights into the prevention and treatment of PCOS.
研究领域:
生殖生物学
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内分泌学
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分子生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）