INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Yongfei Zhang,Depeng Shi,Wenqian Wang,Weiyi Li,Wenhui Li,Lihua Zhao,Lichun Ma,Zhi Peng,Xianyong Sun,Chao Yang
An effective treatment for some disease, such as the model disease acute retinal necrosis (ARN), requires a combination of different drugs which should be administered at a certain interval. The precise sequential and long-term drug release are the critical questions. In this work, the as-prepared chitosan nanoparticles (CS-NPs) coated with hyaluronic acid (HA) were embedded in the aldehyde β-cyclodextrin (ACD)/aminated hyaluronic acid (NHA) hydrogels to synthesize injectable hydrogels loaded with dual drugs named DEX-CS-NPs/GCV-Gel and HA-DEX-CS-NPs/GCV-Gel. In the first 24 h and 48 h, the releases of DEX from DEX-CS-NPs/GCV-Gel were 128.5 % and 82.8 % faster than those from HA-DEX-CS-NPs/GCV-Gel, respectively. There was no DEX released from HA-DEX-CS-NPs/GCV-Gel at the first 7 h, which has never been reported before, although some hydrogel systems loaded with different drugs release different drugs simultaneously at different rate which have been well studied. This is a good start of a precise sequence release. The composite hydrogels possessed appropriate rheology , gel time, degradation performance, and ideal cytocompatibility. The injectable hydrogel loaded with dual drugs presenting a precise sequential and long-term release has great potential in the treatment of diseases requiring combinations of drugs being released sequentially at different treating stages.
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Asian Journal of Pharmaceutical Sciences
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2023
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IF 10.2
Wei He,Daan Fu,Yongkang Gai,Xingxin Liu,Chang Yang,Zhilan Ye,Xu Chen,Jia Liu,Bingcheng Chang
Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and inflammation. Nevertheless, current therapeutic regimens are inadequate to promptly address the vast diversity of potential pathogens. Omiganan, an antimicrobial peptide, has shown promise for neutralizing endotoxins and eliminating diverse pathogens. However, its clinical application is hindered by safety and stability concerns. Herein, we present a nanoscale drug delivery system (Omi-hyd-Dex@HA NPs) that selectively targets infectious microenvironments (IMEs) and responds to specific stimuli for efficient intervention in sepsis. The system consists of omiganan-dexamethasone conjugates linked by hydrazone bonds which self-assemble into nanoparticles coated with a hyaluronic acid (HA). The HA coating not only facilitates IMEs-targeting through interaction with intercellular-adhesion-molecule-1 on inflamed endotheliocytes, but also improves the biosafety of the nanosystem and enhances drug accumulation in primary infection sites triggered by hyaluronidase . The nanoparticles release dual drugs in IMEs through pH-sensitive cleavage of hydrazone bonds to eradicate pathogens and suppress inflammation. In multiple tissue infection and sepsis animal models, Omi-hyd-Dex@HA NPs exhibited rapid source control and comprehensive inflammation reduction, thereby preventing subsequent fatal complications and significantly improving survival outcomes. The bio-responsive and self-delivering nanosystem offers a promising strategy for systemic sepsis treatment in emergencies.
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JOURNAL OF APPLIED POLYMER SCIENCE
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2023
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IF 3
Xinlin Wei,Taijing Zheng,Shunyao Zhu,Xueyuan Liao,Nazi Zhou,Yu Wang,Yue Xu,Meimei Xiong,Rui Liu,Jian Mao,Jie Tao
Magnetic Fe 3 O 4 nanoparticles have attached attention in bone tissue engineering because of their superior magnetism and great biocompatibility. However, some disadvantages such as the potential risk of agglomeration impair their applications. Here, we proposed a hybrid magnetic nanocomposite microgel by the integration of Fe 3 O 4 nanoparticles and digital lighting processing (DLP) three-dimensional (3D) printing technology. The 3D-printed microgels could be precisely customized by printing the mixture of gelatin methacryloyl (GelMA) solution and polydopamine-coated Fe 3 O 4 nanoparticles, in which polydopamine decoration improved the hydrophilicity and distribution of the incorporated Fe 3 O 4 . The degradable microgels could be injected through a 22-G needle while retaining their original shape after injection. Interestingly, the addition of Fe 3 O 4 nanoparticles into GelMA solution displayed improved printing accuracy. Moreover, these magnetic microgels were biocompatible in vitro and in vivo. After induction within osteogenic medium, addition of nanoparticles upregulated the osteogenic gene expression of rat bone mesenchymal stem cells (BMSCs). In a word, this work provides a magnetic microplatform, which shows great potential in bone tissue engineering.
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Food Bioscience
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2023
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IF 5.2
Qiaoli Wu,Bing Liu,Rongxian Yu,Xiaoling Sun,Ziyan Wang,Jun Zhou,Chenyang Lu,Jing Zhang,Jiaojiao Han,Xiurong Su
Osteoarthritis (OA) is a chronic disease associated with bone and muscle degeneration that causes great disturbances to daily lives. Skipjack tuna elastin peptides (STEP) is a kind of small molecule mixed peptides extracted from skipjack tuna bulbus cordis that have multiple active functions, including anti-inflammatory activity. However, it is ambiguous whether STEP reduce OA inflammation. Zebrafish served as a model in the present research for verifying the anti-inflammatory efficacy of STEP. Then, the composition of STEP was figured out by LC-MS/MS analysis, and the potential anti-inflammatory peptides were screened by molecular docking and microscale thermophoresis (MST). Finally, in vitro experiments were conducted on the potential peptides. According to the in vivo findings, STEP protected the cartilage tissues of zebrafish and regulated the expression of inflammatory factors and the JAK2/STAT3 signaling pathway . The in vitro results showed that the potential peptides (LGVGSPPGK, GFDPSR and PGAPGGGFDI) positively regulated the inflammatory responses and the JAK2/STAT3 signaling pathway and were effective in inhibiting extracellular matrix (ECM) degeneration and chondrocyte apoptosis. As a consequence, STEP possess anti-inflammatory and chondroprotective effects and could be a functional product for the alleviation of OA.
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SCIENCE OF THE TOTAL ENVIRONMENT
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2023
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IF 9.8
Jia Luo,Zheng Yan,Yao Shen,Denong Liu,Mingli Su,Jie Yang,Jiarong Xie,Hui Gao,Julin Yang,Aiming Liu
Noise exposure induces metabolic disorders, in a latent, chronic and complex way. However, there is no direct evidence elucidating the relationship between low-intensity noise exposure and nonalcoholic fatty liver disease (NAFLD). Male mice ( n = 5) on high-fat diet (HFD) were exposed to an average of 75 dB SPL noise for 3 months to reveal the effect of noise exposure on NAFLD, where the potential mechanisms were explored. In vivo ( n = 5) and in vitro models challenged with dexamethasone (DEX) were used to verify the role of hypothalamus pituitary adrenal (HPA) axis activation in hepatic lipid metabolism. Typical chronic-restraint stress (CRS, n = 8) was used to explore the role of depression in modifying activity of HPA axis. Finally, animal experiment (n = 8) was repeated to validate the roles of depression and HPA axis activation in NAFLD development. Chronic low-intensity noise exposure exacerbated NAFLD in mice on HFD characterized by hepatocyte steatosis, modified lipid metabolism and inflammation level. Plasma ACTH in H + N group was 1.5-fold higher than that in HFD group. Transcription of glucocorticoid receptor target genes was increased by chronic low-intensity noise exposure in HFD-treated mice. Excessive glucocorticoids mimicking HPA axis activation induced NAFLD in vivo and in vitro . Plasma ACTH increase and lipid storage also occurred in depressive mice stressed by CRS. More interestingly, the same noise exposure simultaneously induced depression in mice, disrupted the HPA axis homeostasis and exacerbated NAFLD in a repeated experiment. Thus, three-month exposure to 75 dB SPL noise was sufficient to exacerbate NAFLD progress in mice, where activation of HPA axis played a critical role. Depression played an intermediate role and contributed to HPA axis activation up-stream of the exacerbation.
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Tissue Engineering and Regenerative Medicine
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2023
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IF 3.6
Zhang Ying,Li Chuan,Wei Qiushi,Yuan Qiang,He Wei,Zhang Ning,Dong Yiping,Jing Zhenhao,Zhang Leilei,Wang Haibin,Cao Xiangyang
BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo . Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.
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MOLECULES
·
2023
·Vol. 28
·期 18
·6619
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IF 4.6
Guozheng Zhao
Based on an indirect competitive method, a novel nano-Au/fluticasone propionate electrochemical immunosensor was successfully fabricated by combining the nanoscale effect, superior conductivity of nano-Au, stable Au−S chemical bond as well as strong interaction between glucocorticoid and the receptor, which was used to simultaneously detect eight kinds of glucocorticoids. The modified immunosensors’ electrochemical properties were explored by means of a cyclic voltammetry (CV) method and electrochemical impedance spectroscopy (EIS) measurements. Two factors (glucocorticoid receptor concentration, incubation time) were studied in order to obtain the optimal results. The immunosensor presents attractive electrochemical performance with a wide linear range (between 0.1 and 1500 ng⋅mL−1) and low detection limit (between 0.057 and 0.357 ng⋅mL−1), realizing the rapid multi-residue detection of a large class of glucocorticoids. Two glucocorticoids (hydrocortisone, triamcinolone) were detected in actual skincare samples, which obtained satisfactory detection results.
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TOXICOLOGY MECHANISMS AND METHODS
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2023
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IF 3.2
Jing Wu,Jiali Chen,Xijing Yu,Yujuan You
Background Prunetin is an O-methylated isoflavone, known for its beneficial properties. However, its specific pharmacological effects in the treatment of osteoporosis (OP) remain poorly understood. This study aims to elucidate the mechanisms underlying the antiosteoporotic effects of prunetin through a combination of bioinformatics analysis and cell experiments.Methods We gathered predicted targets of prunetin from various online platforms. Differential expression analysis of mRNAs in patients with OP was conducted using the Limma package, based on the GSE35959 dataset. A PPI network diagram was visualized and analyzed using Cytoscape 3.7.2 software. Molecular docking was employed to assess the binding affinity between ligands and receptors, and selected key genes were further validated through cell experiments.Results A total of 4062 differentially expressed genes (DEGs) were identified from the GSE35959 dataset. Among these, 58 genes were found to overlap with the targets of prunetin, indicating their potential as therapeutic targets. The enrichment analysis indicated these targets were mainly enriched in MAPK, FoxO, and mTOR signaling pathways. The molecular docking analysis demonstrated that prunetin exhibited strong binding activity with the core targets. Furthermore, cell experiments revealed that prunetin effectively reversed the expression levels of ALB, ESR1, PTGS2, and FGFR1 mRNA in MC3T3-E1 cells treated with dexamethasone (DEX).Conclusion Our research revealed the multi-pathway and multi-target features of prunetin in treating OP, shedding light on the potential mechanisms underlying the effectiveness of prunetin against OP. These findings serve as a theoretical foundation for future drug development in this field.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Bingbing Zhu,Erna Jia,Qimeng Zhang,Yanyan Zhang,Hua Zhou,Ying Tan,Zhennan Deng
Zwitterionic polymers have attracted considerable attention because of their anti-adsorption and unique anti-polyelectrolyte effects and was widely used in surface modification. In this study, zwitterionic copolymers (poly (sulfobetaine methacrylate-co-butyl acrylate) (pSB) coating on the surface of a hydroxylated titanium sheet using surface-initiated atom transfer radical polymerization (SI-ATRP) was successfully constructed. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and Water contact angle (WCA) analysis proved the successful preparation of the coating. The swelling effect caused by the anti-polyelectrolyte effect was reflected in the simulation experiment in vitro, and this coating can promote the proliferation and osteogenesis of MC3T3-E1. Therefore, this study provides a new strategy for designing multifunctional biomaterials for implant surface modifications.
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CARBOHYDRATE POLYMERS
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2023
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IF 11.2
Ying Zhang,Ruirui Ma,Cuiyu You,Xue Leng,Danyang Wang,Shujing Deng,Binyang He,Ziyang Guo,Zelin Guan,Hengyu Lei,Jie Yu,Qinyuan Zhou,Jianfeng Xing,Yalin Dong
Based on the biocompatibility and macrophage targeting of natural polysaccharides , combined with the physiological and pathological characteristics of the gastrointestinal tract and colonic mucosa of ulcerative colitis (UC), we prepare dexamethasone (Dex)-loaded oral colon-targeted nano-in-micro drug delivery systems coated with multilayers of chitosan (CS), hyaluronic acid (HA), and finally Eudragit S100 (ECHCD MPs) using a layer-by-layer coating technique for UC treatment through regulating the M1/M2 polarization of intestinal macrophages. HA/CS/Dex nanoparticles (HCD NPs) are ingested by macrophages via CD44 receptor-mediated endocytosis to regulate M1-to-M2 macrophage polarization and exert anti-inflammatory effects. Moreover, ECHCD MPs show better colon-targeting properties than Dex-loaded chitosan nanoparticles (CD NPs) and HCD NPs which is demonstrated by stronger mucoadhesion to inflamed colon tissues. After oral administration, ECHCD MPs exert significant anti-UC effects. Therefore, ECHCD MPs are proven to be as promising oral colon-targeting drug delivery systems for Dex and have potential application in UC treatment.
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NEPHROLOGY
·
2023
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IF 2.5
Ziyuan Liu,Huilong Xiang,Qin Deng,Wanting Fu,Yang Li,Zejun Yu,Yinsheng Qiu,Zhinan Mei,Lingyun Xu
Aim Inflammation and apoptosis are main pathological processes that lead to the development of hyperuricemic nephropathy (HN). This study aims to explore whether baicalin (BA) and baicalein (BAI) can relieve the damage through PI3K/AKT/NF-κB signal pathway and provide more reliable and precise evidence for the treatment of HN. Methods HN mice were induced by yeast extract with potassium oxonate (PO), and HK-2 cells were induced by monosodium urate (MSU). Molecular docking, western blot, q-PCR, and other methods were used to explore the changes of various indicators in HN mice and HK-2 cells. Results Molecular docking results showed that BA and BAI had good binding ability with PI3K, AKT, p65 and IκBα. BA and BAI significantly ameliorated the levels of renal function, decreased the p-PI3K, p-AKT and p-p65 expression, down-regulated the BAX/BCL2 and CASP3, and blunted the mRNA levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-18 in both renal tissue of HN mice and HK-2 cells induced by MSU. BA and BAI also decreased the oxidative stress level of MSU-induced HK-2 cells. Conclusion BA and BAI were confirmed to attenuate HN through alleviating renal inflammatory and apoptosis in cells and tissues by inhibiting PI3K/AKT/NF-κB pathway. BA and BAI were expected to be developed as new anti-HN drugs.
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Journal of Functional Foods
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2023
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IF 5.6
Yi Wei,Chao Liu,Lujia Li
Geniposide (Gen) is a natural compound derived from Gardenia jasminoides that has anti-inflammatory, antioxidative stress, antiapoptotic, and antitumour properties. However, its mechanisms of action in idiopathic pulmonary fibrosis (IPF) have not been well studied. Recent studies have found that the progression of IPF is influenced by host metabolism. This study investigated the antifibrotic effects and metabolic modulation of Gen. Gen significantly ameliorated pathological injury in the IPF mouse model. Gen reduced the expression of proinflammatory cytokines and inhibited oxidative stress levels. Gen also inhibited NLRP3 inflammasome activation. Untargeted metabolomics analysis revealed that metabolites were affected in the lung. These metabolites were associated with the regulation of arachidonic acid metabolism, histidine metabolism, and tryptophan metabolism. Gen reduced the inflammatory response and oxidative stress and inhibited NLRP3 inflammasome activation in IPF mice. Mechanistically, Gen-mediated treatment of IPF may be linked to the regulation of host metabolism.
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