CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Zhi Zheng,Jian Sun,Jun Wang,Suisui He,Yun Huang,Xu Yang,Yuqi Zhao,Cui-Yun Yu,Hua Wei
The compromised microenvironment after cartilage injury generally leads to low survival or abnormal differentiation of implanted stem cells for fibrocartilage formation with weak mechanical properties. Suitable and safe bionic materials can provide mechanical properties for cartilage repair while promoting cartilage regeneration effects. However, to our knowledge, mechanical strength modulation of therapeutic peptide-based bionic hydrogels remains relatively unexplored, and further application of peptide-based bionic hydrogels in a negative feedback manner for defective cartilage repair has been seldom reported so far. In this study, we reported the first sophisticated design and fabrication of a dual cross-linked peptide-based hydrogel for promoted cartilage regeneration in a feedback-regulated manner. The integration of multiple supramolecular forces including host–guest interactions and extensive hydrogen bonding endow the resulting hydrogels with excellent self-healing and mechanical strength for highly synergistic lubrication properties and compressive performance. More importantly, the unique integrative peptide VPM-pmTGF-β1 can realize on-demand pmTGF-β1 release that is triggered by the MMP-3-responsive cleavage of a VPM sequence. When the VPM-pmTGF-β1-modified hydrogel system is implanted into the cartilage defect sites in a model of SD rats, MMP-3-triggered on-demand pmTGF-β1 release suppresses IκBα/NF-κB signaling pathway-induced cartilage inflammation in a negative feedback manner while promoting the targeted cartilage differentiation of BMSCs for efficient cartilage regeneration. The novel strategy developed herein contributes to a more comprehensive and in-depth understanding of the biological properties of peptide-based hydrogels for cartilage defect repair and provides a simple yet powerful means for clinical translations.
研究领域:
生物材料
·
组织工程
·
再生医学
·
生物力学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2014
·
IF 8.312
Dong Ma,Qian-Ming Lin,Li-Ming Zhang,Yuan-Yuan Liang,Wei Xue
The co-delivery of drug and gene has become the primary strategy in cancer and other disease therapy. To co-deliver hydrophobic drug and functional gene efficiently into tumor cells, a star-shaped copolymer (PP-PLLD-Arg) with a photochemical internalization effect consisting of a porphyrin (PP) core and arginine-functionalized poly( l -lysine) dendron (PLLD-Arg) arms has been designed, and used to co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid for nasopharyngeal cancer therapy. It was found that PP-PLLD-Arg/MMP-9 nanocomplex showed the photo-enhanced gene transfection efficiency in vitro , and could mediate a significant reduce of MMP-9 protein expression in HNE-1 cells. For co-delivery analysis, the obtained PP-PLLD-Arg/DOC/MMP-9 complexes could induce a more significant apoptosis than DOC or MMP-9 used only, and decreased invasive capacity of HNE-1 cells. Moreover, the star-shaped copolymer exhibited better blood compatibility and lower cytotoxicity compared to PEI-25k in the hemolysis and MTT assays , and also showed a good biocompatibility in vivo . Therefore, PP-PLLD-Arg with suited irradiation is a promising non-toxic and photo-inducible effective drug and gene delivery strategy, which should be encouraged in tumor therapy.
研究领域:
药学
·
生物医学工程
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Xu Yao,Jie Zhu,Lin Li,Bo Yang,Bixia Chen,Endong Bao,Xiaohui Zhang
Severe heat stress can cause human and animal heart failure and sudden death, which is an important issue of public health worldwide. Our previous studies in animals showed that myocardial cells injury was critical in the above process, and Hsp90 induction has a definite anti-myocardial injury effect, especially through aspirin (ASA). But the mechanism has not been fully clarified. In this study, an in vitro heat stress model of chicken primary myocardial cells (CPMCs) most sensitive to heat stress was used to explore the cell injuries and corresponding molecular resistance mechanism. We found that heat stress resulted in serious oxidation stress and calcium overload in mitochondria, which destroyed the mitochondrial structure and function and then triggered the cell death mechanism of CPMCs. Hsp90 was proven to be a central regulator for resisting heat-stress injury in CPMCs mitochondria using its inhibitor and inducer (geldanamycin and ASA), respectively. The mechanism involved that Hsp90 could activate Akt and PKM2 signals to promote Bcl-2 translocation into mitochondria and its phosphorylation, thereby preventing ROS production and subsequent cell apoptosis . In addition, Hsp90 inhibited mitochondrial calcium overload to overcome MPTP opening and MMP suppression through the inhibitory effect of Raf-1-ERK activation on the CREB-IP3R pathway. This study is the first to reveal a pivotal reason for heat-stressed damage in chicken myocardial cells at subcellular level and identify an effective regulator, Hsp90, and its protective mechanisms responsible for maintaining mitochondrial homeostasis.
研究领域:
细胞生物学
·
分子生物学
·
心脏病学
·
应激生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF ADHESION AND ADHESIVES
·
2022
·
IF 3.848
Xiaojun Yuan,Qi Wang,Qing Zhao,Zehua Bai,Chen Chen,Haifeng Xie
The activation of matrix metalloproteinases (MMPs) is responsible for degradation of the hybrid layer . The effect of 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) on biodegradation of the hybrid layer remains unknown. This study aimed to evaluate the effects of 10-MDP and its Ca salt on MMP-9 activity and dentin-bonding durability. 10-MDP-Ca salt was synthesized and characterized by X-ray diffraction (XRD) and nuclear magnetic resonance (NMR). The effects of chlorhexidine (CHX), 10-MDP, and 10-MDP-Ca salt on MMP activity were evaluated by in-situ zymography, MMP-9 inhibition assay, and hydroxyproline (HYP) assay. Dentin-resin bonded specimens were fabricated with using CHX or 10-MDP, including Single Bond 2 (Ctr), CHX + Single Bond 2 (CHX), 10-MDP + Single Bond 2 (10-MDP), and SBU (SBU). Micro-tensile bond strength (μTBS) and nanoleakage tests were performed after 24-h or two-years water storage. XRD and NMR confirmed the presence of 10-MDP-Ca salt. The relative inhibition percentages of recombinant MMP-9 for 10-MDP and 10-MDP-Ca salt were 8.04 ± 0.83% and 55.96 ± 1.82% respectively. HYP assay showed that 10-MDP, CHX, and 10-MDP-Ca salt conditioning decreased collagen degradation. Water storage weakened μTBS of all the groups, with the Ctr and CHX groups showing more significant decreases ( P < 0.05). After aging, the Ctr and CHX groups also presented more nanoleakage, and the CHX group showed more in-situ zymography fluorescence than the 10-MDP and SBU groups. The capacity to inhibit MMP-9 activity, decrease HYP release, and reduce nanoleakage of 10-MDP and its salt contribute to improvement of dentin-bonding durability.
研究领域:
牙科材料
·
生物材料
·
牙科学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Huang Dan,Sun Chaoqun,Chen Min,Bai Shuyou,Zhao Xuanna,Wang Weiming,Geng Kang,Huang Wenbo,Zhao Tingting,Wu Bin,Zhang Guilin,Wu Dong,Xu Youhua
Airway inflammation and remodeling are critical pathological changes in asthma, and macrophage activation plays a vital role in this process. Sirtuin 1 (SIRT1) reduces airway inflammation by affecting macrophages in asthma. This study aimed to investigate the potential benefit and underlying mechanism of the SIRT1 agonist bergenin as a treatment for asthma. We performed in vivo and in vitro experiments by establishing a Sirt1fl/fl-LysMcre mouse asthma model and using the alveolar macrophage-like cell line MH-S, respectively. Our results show that Sirt1fl/fl-LysMcre asthmatic mice exhibited more severe airway inflammation and airway remodeling than wild-type mice. As an activator of SIRT1, bergenin attenuated asthmatic airway pathology and reduced production of interleukins 1β, IL-5, IL-6, and matrix metalloproteinase 9 (MMP-9) in wild-type asthmatic mice. However, the therapeutic effects of bergenin were significantly attenuated in Sirt1fl/fl-LysMcre asthmatic mice or following coadministration with the SIRT1 inhibitor EX-527. Further experiments showed that activation of SIRT1 by bergenin deacetylates nuclear factor κB and hinders its nuclear translocation, thereby affecting IL-1β, IL-5, IL-6, and MMP-9 production by regulating transcriptional activity. Our study suggests that bergenin can improve asthma-induced airway inflammation and remodeling by activating SIRT1 in macrophages.
研究领域:
免疫学
·
药理学
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Yingying Xu,Yifan Luo,Zhenzhen Weng,Haichang Xu,Wei Zhang,Qun Li,Huijie Liu,Lubing Liu,Yanmei Wang,Xuexia Liu,Lan Liao,Xiaolei Wang
Periodontitis is a chronic inflammatory disease deriving from dental plaque, characterized by the excessive accumulation of reactive oxygen species (ROS), matrix metalloproteinase (MMP) and other substances, resulting in the destruction of periodontal tissues. At present, the main therapeutic modalities, such as local mechanical debridement and antibiotic delivery, are not only difficult to solve the intractable bacterial biofilm effectively but also tricky to ameliorate the excessive inflammatory response as well as regenerate the impaired periodontal tissues. Herein, we have proposed the TM/BHT/CuTA hydrogel system formed by the self-assembly of the copper-based nanozyme (copper tannic acid coordination nanosheets, CuTA NSs) and the triglycerol monostearate/2,6-di-tert-butyl-4-methylphenol (TM/BHT) hydrogel. The negatively charged TM/BHT/CuTA can retain at the inflammation sites with a positive charge through electrostatic adsorption and hydrolyze in response to the increasing MMP of periodontitis, realizing the on-demand release of the CuTA nanozyme. The released CuTA nanozyme has antibacterial and antiplaque properties. Meanwhile, as a metal-phenolic nanozyme, it can scavenge multiple ROS by simulating the cascade process of superoxide dismutase (SOD) and catalase (CAT). Further, the CuTA nanozyme can modulate the macrophage polarization from M1 phenotype to M2 phenotype through the Nrf2/NF-κB pathway, which reduces the pro-inflammatory cytokines, increases the anti-inflammatory cytokines, and promotes the expression of osteogenetic genes successively, thus relieving the inflammation and accelerating the tissue regeneration of periodontitis. Altogether, this multifunctional nanozyme on-demand release platform (TM/BHT/CuTA) provides a desirable strategy for the treatment of periodontitis.
研究领域:
牙科学
·
纳米技术
·
生物医学工程
·
材料科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·Vol. 15
·期 6
·3008-3022
·
IF 5.1
Danyin Yang,Qi Liu,Qiongyao Xu,Lin Zheng,Silu Zhang,Shan Lu,Guoxun Xiao,Mouming Zhao
This work aimed to investigate the protective effects of collagen hydrolysates containing different contents of Gly-Pro-Xaa tripeptides on UV-induced photoaging mice and to identify potent anti-photoaging peptides. Results showed that oral ingestion of collagen hydrolysates with a higher content of Gly-Pro-Xaa tripeptides (∼11.4%, HCH) dramatically enhanced the absorption of Pro-Hyp, Hyp-Gly, and Gly-Pro-Hyp into the body, which were 1.77-, 2.18-, and 65.07-fold higher in area under the concentration–time curve (AUC) values than that of collagen hydrolysates with a lower content of Gly-Pro-Xaa tripeptides (∼3.8%, LCH), respectively. Furthermore, the protective effects of HCH on the photo-aged skin of mice were significantly stronger than those of LCH in terms of increases in the contents of hyaluronic acid and collagen, improvement in skin elasticity and epidermal thickness, alleviation in inflammation, and decreases in the contents of matrix metalloproteinase-1 (MMP-1) and MMP-3. More importantly, Gly-Pro-Hyp displayed potent anti-photoaging activities comparable to HCH based on an equivalent amount of Hyp. Network pharmacology analysis for potential mechanisms further indicated that Gly-Pro-Hyp might interact with JUN and FOS and regulate IL-17 and TNF signaling pathways. Collectively, our results suggested that HCH had great potential to be applied in functional foods for skin health and Gly-Pro-Hyp was found to be a potent collagen-derived anti-photoaging peptide, which might contribute to the excellent anti-photoaging effects of HCH.
研究领域:
药理学
·
皮肤病学
·
美容护肤品
·
营养保健品
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2023
·Vol. 29
·期 1
·1-17
·
IF 3.4
Yao Zhao,Mirensha Yakufu,Chong Ma,Baicai Wang,Jianhua Yang,Junping Hu
Nonalcoholic steatohepatitis (NASH) is emerging as the primary driver of liver disease‑induced fibrosis. The imperative need for noninvasive biomarkers to ascertain disease progression stage is evident. The present study elucidated the biological roles of hub genes that could potentially serve as diagnostic markers for NASH. Using an in vivo approach, C57BL/6J mice were subjected to a high‑fat and fructose diet (HFFD) for 6, 10, 14, 18 or 22 weeks. Serological biochemical indices were assessed and liver specimens were obtained to identify potential markers linked to the NASH process, employing a comprehensive strategy that combined transcriptomic and histopathological analyses. The HFFD regimen induced hyperlipidemia, obesity and insulin resistance, progressively culminating in NASH with fibrosis over time. The transcriptomic analyses indicated temporal patterns of pivotal gene sets intricately connected to NASH progression, which encompassed processes such as glucose homeostasis, inflammatory responses, reactive oxygen species‑mediated damage, lipid metabolism disruptions and the formation of fibrotic tissue. Among these genes, Serpine1 and Mmp9 demonstrated promising diagnostic potential for NASH, with their intrahepatic mRNA expression levels serving as robust indicators. Moreover, the levels of PAI‑1 (encoded by the Serpine1 gene) and MMP‑9 in the serum of mice demonstrated a parallel increase with the duration of HFFD intervention. In vitro experiments utilizing HepG2 cells further validated these findings, demonstrating a significant elevation in the protein expression levels of both PAI‑1 and MMP‑9 upon exposure to free fatty acids, in agreement with the results of the animal study. Consequently, PAI‑1 and MMP‑9 are promising noninvasive biomarkers for assessing the progression of NASH.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2017
·
IF 13.942
Tianjiao Ji,Jiayan Lang,Jing Wang,Rong Cai,Yinlong Zhang,Feifei Qi,Lijing Zhang,Xiao Zhao,Wenjing Wu,Jihui Hao,Zhihai Qin,Ying Zhao,Guangjun Nie
During pancreatic tumor development, pancreatic stellate cells (PSCs) proliferate exuberantly to secrete extracellular matrix (ECM) in the tumor stroma, which presents major barriers for drug delivery and penetration in tumor tissue. Thus, down-regulating ECM levels via regulation of the PSCs may allow enhanced penetration of therapeutic drugs and thereby enhancing their therapeutic efficacy. To regulate the PSCs, a matrix metalloproteinase-2 (MMP-2) responsive peptide-hybrid liposome (MRPL) was constructed via coassembly of a tailor-designed MMP-2 responsive amphiphilic peptide and phospholipids. By utilizing the MMP-2-rich pathological environment, the pirfenidone (PFD) loaded MRPL (MRPL-PFD) can specifically release PFD at the pancreatic tumor site and down-regulate the multiple components of ECM expressed by the PSCs. This resulted in a significant increase in the penetration of gemcitabine into the tumor tissue and enhanced the efficacy of gemcitabine for pancreatic tumor. Our design tailored for antifibrosis of pancreatic cancer may provide a practical approach to build functional liposomes through supramolecular assembly, and regulation of ECM may be a promising adjuvant therapeutic strategy for pancreatic and other ECM-rich tumors.
研究领域:
药学
·
肿瘤学
·
生物材料
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Science Advances
·
2020
·Vol. 6
·期 18
·
IF 13.117
Chen-Cheng Xue,Meng-Huan Li,Yang Zhao,Jun Zhou,Yan Hu,Kai-Yong Cai,Yanli Zhao,Shu-Hong Yu,Zhong Luo
The rapid development of treatment resistance in tumors poses a technological bottleneck in clinical oncology. Ferroptosis is a form of regulated cell death with clinical translational potential, but the efficacy of ferroptosis-inducing agents is susceptible to many endogenous factors when administered alone, for which some cooperating mechanisms are urgently required. Here, we report an amorphous calcium carbonate (ACC)–based nanoassembly for tumor-targeted ferroptosis therapy, in which the totally degradable ACC substrate could synergize with the therapeutic interaction between doxorubicin (DOX) and Fe2+. The nanoplatform was simultaneously modified by dendrimers with metalloproteinase-2 (MMP-2)–sheddable PEG or targeting ligands, which offers the functional balance between circulation longevity and tumor-specific uptake. The therapeutic cargo could be released intracellularly in a self-regulated manner through acidity-triggered degradation of ACC, where DOX could amplify the ferroptosis effects of Fe2+ by producing H2O2. This nanoformulation has demonstrated potent ferroptosis efficacy and may offer clinical promise.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2017
·Vol. 38
·期 6
·3583-3591
·
IF 2.662
Shilei Zang,Qiling Tang,Fangrui Dong,Huan Liu,Lili Li,Fang Guo,Xuediao Pan,Haorong Lin,Weibin Zeng,Zhaoxu Cai,Qibin Zhong,Ning Zang,Linquan Zang
Curcumol, a polyphenol compound derived from the rhizome of Curcuma, has been established as an antitumor compound against multiple types of cancer, including gastric (GC), lung, liver and breast cancer. However, the molecular mechanisms undelying its anticancer activity in GC are still unclear. In this study, the antitumor efficacy of curcumol was ascertained in human gastric adenocarcinoma MGC-803 cells. An MTT assay was used to assess the viability of the MGC-803 cells treated by curcumol. The results of the Annexin V/propidium iodide (PI) staining followed by fluorescence activated cell sorting (FACS) analysis demonstrated that the cell cycle was arrested in the G2/M phase by curcumol. Annexin V-FITC/PI double staining followed by FACS analysis revealed that curcumol induced apoptosis of MGC-803 cells. FACS analysis after the cells were loaded with a DFCH-DA probe revealed that the level of reactive oxygen species (ROS) increased after the cells were treated with curcumol. In adittion, FACS analysis after the cells were loaded with JC-1 revealed that the level of mitochondrial membrane potential (MMP) decreased after the cells were treated with curcumol. Furthermore, the downregulation of isocitrate dehydrogenase 1 (IDH1) was observed in the MGC-803 cells after being treated with curcumol as determined by western blotting and RT-qPCR. In conclusion, we elucidated the antitumor effect of curcumol on MGC-803 cells and the involved mechanisms related to the induction of apoptosis, the increase of ROS, the decrease of MMP and the downregulation of IDH1.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2015
·
IF 12.881
Kai Han,Shi-Bo Wang,Qi Lei,Jing-Yi Zhu,Xian-Zheng Zhang
Photodynamic therapy faces the barrier of choosing the appropriate irradiation region and time. In this paper, a matrix metalloproteinase-2 (MMP-2) responsive ratiometric biosensor was designed and synthesized for aggregation-induced emission (AIE)-guided precise photodynamic therapy. It was found that the biosensor presented the MMP-2 responsive AIE behavior. Most importantly, it could accurately differentiate the tumor cells from the healthy cells by the fluorescence ratio between freed tetraphenylethylene and protoporphyrin IX (PpIX, internal reference). In vivo study demonstrated that the biosensor could preferentially accumulate in the tumor tissue with a relative long blood retention time. Note that the intrinsic fluorescence of PpIX and MMP-2-triggered AIE fluorescence provided a real-time feedback which guided precise photodynamic therapy in vivo efficiently. This strategy demonstrated here opens a window in the precise medicine, especially for phototherapy.
研究领域:
癌症研究
·
治疗诊断学
·
生物医学工程
·
分子影像
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）