INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
·
IF 6
Xiangyan Liao,Xuanqi Fu,Shuping Wang,Rongjing Zhou,Yun Zhu,Fangying Yu,Cheng Wang,Jianhao Wang
Chronic non-healing wounds pose a clinical burden, necessitating advanced dressings that modulate the healing microenvironment and accelerate tissue regeneration. Herein, we developed a hydrogel-based dressing by integrating pig skin-derived reconstituted lipid nanoparticles (PS-rLNPs) with FDA-approved sodium alginate (SA), termed PS-rLNPs-SA. PS-rLNPs were fabricated via a solvent injection method with lipids from fresh pig skin, which were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and liquid chromatography-mass spectrometry (LC-MS). PS-rLNPs exhibited uniform spherical morphology with hydrated particle size of 91.3 nm, excellent colloidal stability in physiological environments, and were mainly composed of triglycerides (77.9%) and phosphatidylcholine (11.6%)—lipids that synergistically support cell metabolism and membrane interaction. In vitro , PS-rLNPs promoted proliferation and migration of 3 T3 and L929 fibroblasts in a concentration-dependent manner (optimal at 300 μg/mL) without cytotoxicity, primarily via clathrin-mediated endocytosis and lysosomal escape. PS-rLNPs-SA hydrogel, prepared via in-situ calcium crosslinking, displayed shear-thinning behavior, injectability, and biocompatibility, enabling sustained release of PS-rLNPs at the wound site. In murine full-thickness skin defect model, PS-rLNPs-SA significantly accelerated wound closure (healing rate of 93.26% on Day 10), outperforming free PS-rLNPs and blank SA hydrogel. Histopathological and immunohistochemical analyses showed PS-rLNPs-SA enhanced regeneration, reduced inflammatory infiltration, promoted collagen deposition, and increased neovascularization (CD31 + vessels) and cell proliferation (Ki-67 + cells). Furthermore, in vitro hemolysis assays and in vivo major organ histology verified the biosafety of PS-rLNPs-SA. This work introduces promising natural lipid-based nanoplatform for wound repair, offering a novel strategy for developing clinically translatable wound dressings.
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高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Wei Wei,Yuanyuan Yao,Hongyuan Bi,Wenxin Xu,Yan Gao
Our previous findings revealed that hsa_circ_0068,888 was markedly down-regulated in the plasma of patients with sepsis-associated acute kidney injury (AKI). However, its molecular mechanism in AKI remains unclear. Herein, we explored the role of hsa_circ_0068,888 in AKI. Human renal proximal tubular cell line HK-2 was stimulated with lipopolysaccharide (LPS) to mimic AKI in vitro . Decreased hsa_circ_0068,888 expression was observed in AKI cell model. The overexpression of hsa_circ_0068,888 significantly increased the viability of LPS-stimulated HK-2 cells, whereas hsa_circ_0068,888 downregulation showed the opposite effect. Furthermore, LPS triggered inflammatory response and oxidative stress , which was inhibited by hsa_circ_0068,888 overexpression and enhanced by hsa_circ_0068,888 down-regulation. Hsa_circ_0068,888 overexpression suppressed the activation of nuclear factor-κB (NF-κB) pathway triggered by LPS as evidenced by decreased p-p65 protein level and nuclear translocation of p65 in hsa_circ_0068,888 overexpressed cells. Additionally, we proved that hsa_circ_0068,888 targeted microRNA-21–5p (miR-21–5p). The expression of miR-21–5p was markedly increased and was negatively regulated by hsa_circ_0068,888 in LPS-stimulated HK-2 cells. Furthermore, we demonstrated that miR-21–5p overexpression reversed the effects on cell viability , inflammatory response, oxidative stress, and NF-κB pathway induced by hsa_circ_0068,888 overexpression in LPS-stimulated HK-2 cells. Overall, these results implied that hsa_circ_0068,888 shows a protective effect on AKI by sponging miR-21–5p. Hence, up-regulation of hsa_circ_0068,888 might be a potential strategy in treatment for AKI.
研究领域:
分子生物学
·
细胞生物学
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肾脏病学
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PubMed
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-PLANT
·
2021
·Vol. 57
·期 3
·372-379
·
IF 2.252
Li Xiuyu,Zhang Zijie,Ren Yunhui,Feng Yue,Guo Qi,Dong Li,Sun Yuhan,Li Yun
Tetraploid black locust ( Robinia pseudoacacia L.) has advantages over diploid varieties in growth and stress resistance. Previous studies had shown that tetraploid black locust can be induced only by treating shoot tips of the germinating seeds with colchicine. In order to establish a simpler and more efficient tetraploid induction method in black locust, we induced tetraploid plants by treating the hypocotyls from in vitro –grown seedlings with different concentrations of colchicine, and then provided a method for tetraploid identification based on stomatal size and density in this study. The highest induction efficiency was 53.33% by treating hypocotyl explants with 70 mg·L −1 colchicine for 2 d. Tetraploid black locust was significantly different from diploid in morphological characteristics. Leaf area, leaf thickness, chlorophyll content, stomatal length, and stomatal width were greater in tetraploid plants than in diploid plants, whereas the opposite was true for leaf aspect ratio, stomatal index, and stomatal density. The differences in stomatal size and density between diploid and tetraploid were nearly two times; therefore, size and density of stomata can be used as a stable and distinct marker to rapidly screen tetraploids. The results of this study suggested that the hypocotyl was an ideal material to induce tetraploid black locust in vitro and confirmed that stomatal size and density could be an effective and reliable marker to identify ploidy level in black locust.
研究领域:
植物科学
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生物技术
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分子生物学
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2021
·
IF 5.268
Qiang Li,Dongsheng Fu,Jie Zhang,Hong Yan,Huifang Wang,Baolong Niu,Ruijie Guo,Yiming Liu
In this study, a new type of polypeptide, crosslinked methoxy poly(ethylene glycol)-g-poly(aspartic acid)-g-tyrosine (CPPT), was synthesized via a green and simple one-pot polymerization method. With the disulfide-crosslinked interlayer and the CaP shell, the pH and redox dual-sensitive polypeptide-based organic-inorganic hybrid nanoparticles encapsulated curcumin (Cur) into the hydrophobic core of micelles and loaded doxorubicin hydrochloride (DOX) on the hydrophilic segment of micelles as well as CaP shell. The spherical Cur- and DOX-loaded nanoparticles (CPPT@CaP-CD) showed a hydrodynamics size of about 157.9 ± 3.9 nm. The premature leakage of drugs from the nanoparticles at physiological pH was efficiently restrained because of the enhanced structure integrity, whereas at acidic and hypoxia microenvironment the release of both drugs was promoted due to the rapid dissolution of the CaP shell and the break of the disulfide crosslinked network, facilitating the stimuli-responsive controllable drugs release. In vitro anticancer activity evaluation revealed that the co-loaded nanoparticles presented higher cytotoxicity against A549 cells compared with that of the free combination of Cur + DOX. Confocal laser scanning microscopy observation indicated that more DOX and Cur were released into the nucleus triggered by the up-regulated intracellular glutathione (GSH) concentration and decreased pH, displaying enhanced cell uptake. The self-assembling polypeptide-based dual-sensitive drug co-delivery system could be a promising platform for efficient chemotherapy.
研究领域:
生物材料学
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药物递送系统
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肿瘤学
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PubMed
高影响因子
Small
·
2021
·Vol. 17
·期 7
·2005865
·
IF 13.281
Peipei Yang,Jia Tao,Fengfeng Chen,Yuying Chen,Jiaqi He,Kui Shen,Peng Zhao,Yingwei Li
Nanozyme-based chemodynamic therapy (CDT) has emerged as an effective cancer treatment because of its low side effects and without the requirement of exogenous energy. The therapeutic effect of CDT highlights the pivotal importance of active sites, H 2 O 2 supplement and the glutathione (GSH) depletion of a nanozyme. The construction of a single kind of catalyst with multiple functions for the enhanced CDT is still a big challenge. In this work, seven types of bimetallic nanoparticles are synthesized using a metal–organic framework (MOF) as a stable host instead of a Fenton or Fenton-like ions supplier. Among them, Cu-Pd@MIL-101 with an alloy loading of 9.5 wt% modified by PEG (9.5% CPMP) is found to exhibit the highest peroxidase (POD) like activity combined with a superoxide dismutase (SOD) mimic activity and the function of GSH depletion. The in vivo results suggest that the stable and ultrafine nanoparticles possess favorable CDT effect for tumor and good biosafety as well as biocompatibility. This work has provided a credible strategy to construct nanozymes with an excellent activity and may pave a new way for the design of enhanced tumor CDT treatment.
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物化学
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生物医学工程
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PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2021
·
IF 2.646
Qiang Li,Dongsheng Fu,Jie Zhang,Tianyang Li,Huifang Wang,Wenjuan Hou,Baolong Niu,Ruijie Guo,Yiming Liu
Encapsulation of therapeutic molecules into nanocarrier is an extensively explored strategy to treat cancer more effectively. In this study, pH-responsive targeting dual-agent delivery nanoparticles were prepared, into which hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic curcumin (CUR) were entrapped. Tyrosine (Tyr) was grafted onto poly(aspartic acid) (PASP) to produce PASP-Tyr, the following reaction between hyaluronic acid (HA) and ethylenediamine (EDA) modified PASP-Tyr formed the nanocarrier HA-EDA-PASP-Tyr (HEPT), and the loading capacity was up to 50.9 ± 4.3% for CUR and 26.0 ± 1.9% for DOX. The spherical HEPT with the mean particle size of 142.9 ± 11.4 nm expanded and deformed into petaloid pattern with an increased size of about 2 µm when triggered by the acidic microenvironment. In vitro anticancer activity evaluation revealed that the co-loaded (DOX+CUR)@HEPT nanoparticles presented higher cytotoxicity against HCT-116 cells compared with that of the free combination of (DOX+CUR). Confocal laser scanning microscopy observation indicated that HEPT carrier promoted cellular uptake of drugs by means of active targeting capacity of HA ligand. With high loading capacity and tailored carrier structure, the nanoparticles formulations may offer a new strategy for cancer treatment.
研究领域:
药剂学
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肿瘤学
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生物材料
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PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Wu Xiaodong,Li Pengpeng,Cheng Jian,Xu Qiang,Lu Beiji,Han Conghui,Huo Weiling
Objective: Osteoarthritis (OA) is a common subtype of arthritis. To date, treatment of OA focuses primarily on alleviating pain and improving joint function. The lack of a vascular system within synovial joints and the rapid removal of agents due to synovial exchange hinder continuous delivery of OA drugs. However, these obstacles are being addressed by promising nanoscale drugs.Methods: We synthesize and assemble a hydrogen peroxide [H2O2, belongs to the category of active oxygen species (ROS)]-sensitive nanomicelle, which is loaded with the anti-inflammation drug dexamethasone and chondrogenic differentiation factor cartilage-derivedmor-phogeneticprotein-1. The micelle can induce bone marrow mesenchymal stem cells to repair cartilage while inhibiting joint inflammation.Results: The prepared nanoparticles were of uniform size and displayed an obvious core-shell structure. Under H2O2 stimulation, the shell layer could be removed gradually. The drug-loaded micelle effectively inhibited proliferation of activated macrophages, induced macrophage apoptosis with an anti-inflammatory effect, and caused the BMSCs to differentiate into chondrocytes.Conclusion: This work provides an experimental and theoretical basis for further development of a drug-loaded micelle in the healing of osteoarthritis.
研究领域:
药学
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生物医学工程
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骨科
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纳米技术
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PubMed
高影响因子
BMC CANCER
·
2021
·Vol. 21
·期 1
·1-14
·
IF 4.43
Zhao Wei,Zhao Jing,Guo Xiao,Feng Yujie,Zhang Bingyuan,Tian Lantian
Background Cholangiocarcinoma is a common malignant tumor of digestive system. LncRNA metallothionein 1 J, pseudogene (MT1JP) has been reported to play tumor-suppressing roles in multiple cancers. However, its effect on cholangiocarcinoma has not been evaluated. Methods The expression of MT1JP in intrahepatic cholangiocarcinoma specimens and paired para-carcinoma tissues were detected by real-time PCR. The overexpression plasmid and siRNA of MT1JP were transfected into intrahepatic cholangiocarcinoma cells to change the expression levels of MT1JP. CCK-8, flow cytometry and transwell assays were performed to measure proliferation, cell cycle transition, apoptosis, migration and invasion. Dual-luciferase reporter assay, real-time PCR and western blot were carried out to screen the miRNA bound by MT1JP. In addition, xenograft experiment was used to determine the tumorigenesis of cholangiocarcinoma cells in nude mice. Results MT1JP was downregulated in intrahepatic cholangiocarcinoma specimens, and its expression was related with TNM stage and lymph node metastasis. Overexpression of MT1JP inhibited proliferation, cell cycle transition, migration and invasion, and induced apoptosis in intrahepatic cholangiocarcinoma cells. The knockdown of MT1JP led to opposite results. MT1JP bound to miR-18a-5p to facilitate the expression of fructose-1,6-bisphosphatase 1 (FBP1). MiR-18a-5p was increased in intrahepatic cholangiocarcinoma samples, and its expression was negatively correlated with that of MT1JP. In addition, MT1JP also suppressed tumorigenesis in nude mice. Conclusions MT1JP alleviated proliferation, migration and invasion, and induced apoptosis in cholangiocarcinoma cells by regulating miR-18a-5p/FBP1 axis. These findings may provide novel insights for clinical diagnosis and treatment of cholangiocarcinoma.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
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高影响因子
CHEMISTRY OF MATERIALS
·
2020
·
IF 9.567
Shuming Dong,Yushan Dong,Tao Jia,Fangmei Zhang,Zhao Wang,Lili Feng,Qianqian Sun,Shili Gai,Piaoping Yang
Tailored to the peculiar tumor microenvironment, Fenton reaction-based chemodynamic therapy (CDT) has attracted considerable attention for tumor treatment. However, the efficacy of CDT is highly limited by both H2O2 overproduction and the low activity of catalysts at the tumor site. Herein, a novel magnetic targeting nanoplatform (γ-Fe2O3-GOx-DMSN) has been designed by simply depositing ultrasmall γ-Fe2O3 nanoparticles and natural glucose oxidase (GOx) into the large mesopores (∼13 nm) of dendritic mesoporous silica (DMSN) spheres for near-infrared (NIR) light-enhanced CDT efficacy. In this structure, GOx can effectively consume glucose in the tumor cells to induce a decrease in the pH value and generate a considerable amount of H2O2, both of which promote subsequent Fenton reaction. These ultrasmall γ-Fe2O3 nanoparticles not only serve as an efficacious Fenton catalyst for degradation of the increased H2O2 within the tumor to produce highly toxic hydroxyl radicals (•OH) but also exhibit high photothermal therapy (PTT) efficiency upon irradiation with 808 nm light. Importantly, the generated hypothermia can significantly accelerate the Fenton process, thereby enabling a synergetic PTT/hypothermia-enhanced CDT effect. Our work manifests a proof of concept of H2O2-evolving and NIR-enhanced CDT, providing a new perspective for cancer therapy.
研究领域:
生物医学工程
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肿瘤学
·
纳米医学
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高影响因子
INTERNATIONAL JOURNAL OF NEUROSCIENCE
·
2020
·
IF 2.107
Xinguo Li,Jing Tong,Jihui Liu,Yibao Wang
Objective Alcohol abuse can cause severe injury to human brain. Astrocytes are the most abundant nonneuronal cells that function to maintain the brain homeostasis. In present study, we aimed to investigate the role of ROCK2 in astrocytes exposed to alcohol.Methods Astrocytes were transfected with lentivirus (LV)-anti-ROCK2 vector to downregulate the expression of ROCK2. The ROCK2 expression in mRNA and protein level was analyzed by real-time PCR and Western blotting, respectively. Cytokines or indicators involved in inflammation and oxidative stress were determined by assay kits. Proteins involved in nuclear factor kappa B (NF-κB) signaling pathway and NOD-like receptor protein 3 (NLRP3) inflammasome were analyzed by Western blotting.Results Alcohol exposure dramatically upregulated ROCK2 expression and lactate dehydrogenase (LDH) activity in astrocytes. On the contrary, transfecting with LV-anti-ROCK2 vector downregulated ROCK2 expression and LDH activity in astrocytes, demonstrating that downregulation of ROCK2 alleviated alcohol-induced astrocytic injury. Furthermore, downregulation of ROCK2 attenuated alcohol-induced inflammation by reducing the levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-6) and enhanced the level of anti-inflammatory IL-10. Downregulation of ROCK2 also attenuated alcohol-induced oxidative stress by reducing the reactive oxygen species (ROS) production, as well as enhancing the activity of anti-oxidative superoxide dismutase (SOD) and glutathione (GSH). More importantly, downregulation of ROCK2 inhibited the activation of NF-κB signaling pathway and NLRP3 inflammasome.Conclusion Therefore, ROCK2 could be a potential target to treat alcohol-induced astrocytic injury and the downregulation of ROCK2 might be a promising approach to protect against alcohol-induced astrocytic injury.
研究领域:
神经科学
·
药理学
·
细胞生物学
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PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Yuanyuan Yang,Xin Liu,Wen Ma,Qing Xu,Gui Chen,Yufei Wang,Haihua Xiao,Nan Li,Xing-Jie Liang,Meng Yu,Zhiqiang Yu
External stimuli-responsive nanomedicine with desirable repetitive on-demand drug release character is postulated to greatly accommodate patients' flexible medication regime. To this object, light-activatable liposomes (Pt/Ce6-LP) integrated with both a Ce6 photodynamic component and a tetravalent platinum prodrug (Pt(IV)) chemotherapeutic component are engineered. This multifunctional system was rationally designed using unsaturated phospholipid to achieve repetitive on-demand drug release under discontinuous light irradiation, thus performing chemo-photodynamic therapy effect and immunopotentiation in hypoxic tumor. Furthermore, glutathione (GSH) consumption during transformation from Pt(IV) prodrug to Pt(II) can avoid depletion of reactive oxygen species (ROS) in photodynamic therapy (PDT). Note this positive feedback loop appears to remodel the redox balance of H 2 O 2 and GSH in tumors, alleviating the hypoxic tumor microenvironment . The alleviated hypoxia is found to be critical to the enhancement of PDT efficacy, reversal of cisplatin resistance in tumors, and polarization of tumor-associated macrophages (TAMs) to the immunocompetent M1-phynotype. Pt/Ce6-LP with light radiation demonstrates significant antitumor effect and persistent post-medication inhibition in patient-derived tumor xenograft model of hepatocellular carcinoma.
研究领域:
纳米医学
·
癌症治疗
·
药学
·
生物医学工程
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PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2020
·Vol. 45
·期 12
·2926-2938
·
IF 3.038
Tian Jun,Yang Lei,Wang Pengfei,Yang Lijun,Fan Zhenzeng
With millions of traumatic brain injury (TBI) patients every year, TBI is regarded as one of the leading causes of human death and disability. Calcitonin gene-related peptide (CGRP) has been domenstrated to be a potential therapeutic target for TBI. However, the detailed effect and underlying mechanism of CGRP on the injured brain after TBI has hardly been investigated. In this work, we established TBI models of mice and injected CGRP before and after modelling to study its effects on the brain lesion, neurological functions and behaviours, neuron apoptosis and autophagy after TBI. Impacts of introduced CGRP on the activation of Akt/mTOR signalling in the cortical tissues surrounding injured areas after TBI were also evaluated. It was found that CGRP was reduced after TBI, and gradually restored over time. CGRP administration significantly restored the brain lesion induced by TBI. The permeability of blood–brain barrier and brain edema was increased dramatically after TBI, which was ameliorated by exogenous CGRP. Moreover, several neurological behaviour tests were performed, showing that CGRP introduction also relieved the cognitive abilities of mice which were impaired after TBI. Enhancing apoptosis and autophagy of neurons in the cortical tissues of injury sites following TBI were also alleviated by CGRP administration. Besides, CGRP-treated brain cortical tissues showed increased activation of Akt/mTOR signalling after TBI. Therefore, the results suggest that exogenous CGRP plays a neuroprotective role in the injuryed brain after TBI, to relieve cell apoptosis and autophagy, at least partially through Akt/mTOR signalling pathway. This finding also provides more evidence for the treatment of TBI through introducing exogenous CGRP or its related drugs.
研究领域:
神经科学
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药理学
·
分子生物学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）