INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Jiuheng Ruan,Chao Liu,Jiaqi Wang,Ting Zhong,Peng Quan,Liang Fang
This study sought to provide approach for evaluating and predicting the efficacy and safety of permeation enhancers on the basis of their kinetic distribution behavior in the skin dictated by physicochemical properties. Herein, the efficacy-safety regularity of eight permeation enhancers were studied with ex vivo skin permeation study, small-angle X-ray scattering, MTT assay, H&E staining, and in vivo skin erythema analysis, classifying into the following three categories: high enhancement–low irritation, medium enhancement–high irritation, and low enhancement–low irritation. These three modes were positively correlated with the distribution amount of permeation enhancers in the skin layers and verified by the in vitro tape-stripping study. The kinetic parameter, effective-safety index ( I ES ), was proposed to describe the regularity of enhancement effect tendency and irritation risk, and the relationship between I ES and physicochemical properties of permeation enhancers was analyzed with multiple regression analysis. According to the results of modulated temperature differential scanning calorimetry and dielectric spectrum, permeation enhancers with high lipophilicity and low polarity had I ES > 1, suggesting high enhancement effect and low irritation due to their higher affinity with the stratum corneum (SC) than with epidermis (EP). Permeation enhancers with medium lipophilicity and medium polarity exhibited 0 < I ES ≤ 1, showing medium enhancement effect and high irritation, as determined by their comparable affinity with the SC and epidermis (EP). However, permeation enhancers with low lipophilicity and high polarity had I ES → 0, demonstrating low enhancement effect and irritation, as indicated by their poor affinity with the SC. In summary, different physicochemical properties of permeation enhancers influenced their affinities with skin layers, resulting in their different enhancement effect and irritation potential. This study will provide a theoretical basis and criteria for evaluating and predicting the safety and efficacy of permeation enhancers, which will enable a more rational selection of permeation enhancers in the optimization of transdermal patches .
研究领域:
药剂学
·
药理学
·
生物物理学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2020
·
IF 5.115
Haiyan Wang,Qiuping Xu,Hui Hu,Chunling Shi,Ziyan Lin,Huixi Jiang,Huaipu Dong,Jing Guo
Background Relying on surface topography alone to enhance the osteointegration of implants is still inadequate. An effective way to combine long-term ion release and surface topography to enhance osteogenic property is urgently needed. Purpose The objective of this study is to fabricate a long-term strontium ion release implant system and confirm the biological function in vitro and in vivo. Methods The biomimic surface was fabricated through alkali-heat treatment and magnetron sputtering. The in vitro biological function assays were determined by MTT, fluorescence staining, alkaline phosphatase activity, extracellular mineralization, and quantitative real-time polymerase chain reaction assays. The in vivo experiments were detected by micro-CT, HE staining and Masson staining. Results The biomimic surface structure has been successfully fabricated. The in vitro cell assays determined that AH-Ti/Sr90 possessed the best biological function. The in vivo experiments demonstrated that AH-Ti/Sr90 could promote osteointegration significantly under both in normal and osteoporotic conditions. Conclusion We determined that AH-Ti/Sr90 possesses the best osteogenic property, long-term ion release capacity and osteointegration promotion ability. It has potential clinic application prospects.
研究领域:
生物材料
·
生物医学工程
·
骨科
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Meitao Duan,Dan Zhou,Junfang Ke,Yan Chen,Wenfeng Wu,Yue Li,Jungang Ren,Li Wang,Zhiqiang Zhang,Chen Wang
Receptor and ligand binding mediated targeted drug delivery systems (DDS) sometimes fail to target to tumor sites, and cancer cell membrane (CCM) coating can overcome the dilemma of immune clearance and nonspecific binding of DDS in vivo. In order to enhance the targeting ability and improve the anti-tumor effect, a dual targeting DDS was established based on U87MG CCM mediated homologous targeting and cyclic peptide RGD mediated active targeting. The DDS was prepared by coating RGD doped CCM onto doxorubicin (DOX) loaded liposomes. The homologous and active dual targeting ability endowed the DDS (RGD-CCM-LP-DOX) exhibited superior cancer cell affinity, improved tissue distribution and enhanced anti-tumor effects. In vivo pharmacodynamic studies revealed that RGD-CCM-LP-DOX exhibited superior therapeutic effect compared with homologous targeting CCM-LP-DOX and non-targetable LP-DOX injection. H&E staining, Ki 67 staining and TUNEL staining confirmed that RGD-CCM-LP-DOX not only increased anti-tumor efficacy, but also reduced tissue toxicity by changing the distribution in vivo . The experimental results showed that the RGD doped CCM camouflaged liposome DDS is a better choice for chemotherapeutics delivery.
研究领域:
药学
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Research and Technology-JMR&T
·
2023
·
IF 6.4
Qiaoyun Liu,Yifeng Yu,Changjiang Liu,Yuhang Liu,Liangjie Yuan,Zheng Wang,Aixi Yu
Lanthanum (La) compounds have attracted much attention because of low toxicity and biocompatibility. In this study, a series of La-doped magnesium phosphate composites bone repair materials (LMPCs) were prepared by the precursor method, in which the molar ratio of lanthanum was 1%, 3% and 5%, respectively. The results of X-ray powder diffraction, scanning electron microscope and compressive strength test show that La-doped magnesium phosphates (LMPs) synthesized by the precursor method have uniform particle distribution, high purity and excellent degradability. In vitro research results show that LMPCs exhibited reliable biosafety and excellent bioactivity. The introduction of lanthanum enhances the antibacterial activity of Escherichia coli and Staphylococcus aureus of the composite. Furthermore, the combined system of released La 3+ and Mg 2+ is more conducive to promoting the proliferation of mesenchymal stromal cells (MSC) and angiogenesis of human umbilical vein endothelial cells (HUVECs) when the content of lanthanum is 3% (referred to as LMPC-2). By up-regulating the expression of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (RUNX2), LMPC-2 is prominent in promoting osteogenic differentiation, and mineralized calcium deposition in vitro . Moreover, the results of micro-CT, H&E and Masson staining confirmed the beneficial effect of the combined system of La 3+ and Mg 2+ on the repair of rat skull defects in vivo . These achievements will provide new strategies for improving the biological activity of LMPCs and provide reference value for bone repairing in the clinic.
研究领域:
生物材料
·
生物医学工程
·
组织工程
·
骨再生
✓ 已验证
产品关联
DOI
高影响因子
Asian Pacific Journal of Tropical Medicine
·
2019
·
IF 1.772
Ni Pan-Li,Tian Shu-Hong,Yang Zhao-Xin,Zhang Jun-Qing,Yang Fan,Zhong Li-Fan,Gan Lian-Fang,Huang Mian-Qing,Huang Ling
Objective: To explore the effect of Feng-liao-chang-wei-kang ( FLCWK ) on acute and chronic gastroenteritis, synergistic effect on the growth inhibitory effect with 5-fluorouracil (5-FU) on colorectal cancer and its underlying mechanisms. Methods: In the in vitro study, HT-29 cells were divided into 5-FU alone, FLCWK alone and coadministration groups. The MTT assay was used to analyze the proliferation of HT-29 cells at 24 h. Flow cytometry was used to observe the apoptosis, cycle of colorectal cancer HT-29 cells at 24 h. In the in vivo experiment, The subcutaneous transplantation tumor model of colorectal cancer HT-29-Luc was established with nude mice. All mice were randomly divided into 5-FU alone, FLCWK alone and coadministration groups according to body weight. During administration, the Interactive Video Information System small animal live imaging system was used to monitor the growth of subcutaneous transplantation in nude mice. The model of colitis-associated colorectal cancer (CACC) was established with BALB/c mice. BALB/c mice were randomly divided into the normal control group, the model control group, and the FLCWK group. At the end of the administration, the pathological status was detected by HE staining. Cell apoptosis of tumor tissue tumor and colon tissues were observed by TUNEL staining and TUNEL green fluorescence. The protein expression of Caspase 3, p-STAT3, Bcl-2, Bax and P-gp in tumor tissues tumor and colon tissues were tested by using immunohistochemical assay. Results: FLCWK and 5-FU coadministration suppressed HT-29 cell viability and induced S phase arrest and apoptosis compared to treatment with 5-FU alone. Furthermore, compared to treatment with 5-FU alone, coadministration of FLCWK and 5-FU obviously reduced tumor volume and weight and induced apoptosis through decreasing p-STAT3 and P-gp and increasing Caspase 3 protein expression in a murine xenograft tumor model. Moreover, the result revealed decreased number and size of tumors following FLCWK protective administration, downregulated p-STAT3 and Bcl-2 levels and upregulated Bax and Caspase 3 expression in mice with CACC. Conclusions: FLCWK has synergistic effects with 5-FU on colorectal cancer by suppressing the STAT3 pathway and downregulating P-gp expression. Furthermore, FLCWK administration suppresses CACC tumorigenesis by inhibiting the STAT3 pathway.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Haibo Lou,Jian Wang,Yaping Wang,Yongdong Gao,Wei Wang
In this study, the probiotic characteristics of Enterococcus faecalis SN21-3 were explored by genotype and phenotype, and the safety of this strain was evaluated in vitro and vivo . The complete genome sequence of E. faecalis SN21-3 revealed basic genetic information and corresponding genes underlying its probiotic characteristics. In vitro experiments were performed with E. faecalis SN21-3, which showed prominent antimicrobial activity and excellent abilities of resistance to simulated gastrointestinal fluid, cholesterol assimilation, adhesion, and antioxidant. In addition, E. faecalis SN21-3 was susceptible to the most common antimicrobial agents, did not contain transferable resistance gene and pathogenic gene, and did not perform haemolysis reactions and gelatinase activity in vitro . Furthermore, in vivo experiments demonstrated that feeding E. faecalis SN21-3 to broilers for 28 days did not significantly affect their normal growth or blood biochemistry parameters. Moreover, H&E staining showed no evidence of lesions in the heart, liver, spleen, or kidney of the broilers. No migration of E. faecalis SN21-3 was observed in the heart, liver, spleen, kidney, or blood samples during the feeding trial, indicating that the bacteria did not cause infections. In summary, E. faecalis SN21-3 exhibits numerous probiotic characteristics and is sufficiently safe for use as a novel animal probiotic.
研究领域:
微生物学
·
动物科学
·
基因组学
·
食品科学
✓ 已验证
产品关联
DOI
高影响因子
CURRENT NEUROVASCULAR RESEARCH
·
2023
·Vol. 20
·期 4
·480-492
·
IF 2.1
Li Xuejing,Wang Ying,Zhou Xiang,Wang Hui,Xu Jiang
Background: Increasing evidence shows that electroacupuncture pretreatment (EP) plays a crucial role in cerebral ischemia-reperfusion (I/R) injury, and cerebral I/R injury is the most serious complication of ischemic stroke treatment. The role of miR-155-5p in cerebral I/R injury has
been studied, but the regulation of EP on miR-155-5p has not been reported.Methods: The middle cerebral artery occlusion (MCAO) mice were used to investigate the role of EP in cerebral I/R injury. Longa and modified neurological severity scores (mNSS) were used to evaluate neurological
impairment. HE staining and TUNEL staining were used to evaluate brain injury. The expressions of miR-155-5p, Yin Yang 1 (YY1) and p53 were detected by qRT-PCR. The expressions of related proteins were detected by western blot. The binding of YY1 to miR- 155-5p was verified by dual-luciferase
reporter assay and chromatin immunoprecipitation (ChIP) assay. Mice brain microvascular endothelial cells (BMECs) were isolated and cultured for in vitro experiments. Oxygen-glucose deprivation/reoxygenation (OGD/R) was used to verify the role of YY1, p53 and miR-155-5p in cerebral I/R injury
in vitro.Results: MCAO modeling induced brain injury, apoptosis, and increased levels of miR-155-5p, YY1, and p53. EP markedly alleviated brain injury and reduced levels of miR-155-5p, p53, and YY1. miR-155 agomir markedly increased the expression of miR-155-5p and p53. miR-155 antagomir
decreased the levels of miR-155-5p and p53. Dual-luciferase reporter and ChIP assay verified that YY1 regulated miR-155-5p expression. YY1 shNRA greatly decreased miR-155-5p and p53. Inhibition of p53 decreased miR-155-5p expression. Both miR-155-5p inhibitor and YY1 shRNA promoted proliferation,
inhibited apoptosis, and decreased levels of ICAM-1 and Eselectin of OGD/R-treated BMECs. Inhibition of p53 strengthened the effect of miR-155-5p inhibitor and YY1 shNRA on BMECs.Conclusion: Electroacupuncture pretreatment alleviates cerebral ischemia-reperfusion injury by regulating the
YY1/p53/miR-155-5p axis.
研究领域:
神经科学
·
分子生物学
·
针灸
·
脑血管疾病
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Zhang Yunxia,Wu Xiaoxiao,Li Ruoqi,Sui Mengru,Li Guoyin,Fan Shuhua,Yang Mingsheng,Liu Qiuping,Liu Xiaomeng,Wu Changjing,Li Lili
Sodium Danshensu (SDSS) is extracted from Salvia miltiorrhiza and has many pharmacological effects. However, little is known about its effects on muscle fiber formation and metabolism. Here, we aimed to investigated the role and molecular mechanisms of SDSS in modulating the formation of skeletal muscle fiber. C2C12 cells were incubated in differentiation medium with or without SDSS for 4 days. C57BL/6 mice were orally administered SDSS by gavage once a day for 8 weeks. Grip strength, treadmill, muscle weight, western blotting, qPCR, immunofluorescence staining and H&E staining were performed. SDSS target proteins were searched through drug affinity responsive target stability (DARTS) and mass spectrometry analysis. Furthermore, molecular docking was carried out for Pyruvate kinase M1 (PKM1). The effect of PKM1 on myosin heavy chain (MyHCs) gene expression was verified by knockdown of PKM1 experiment. SDSS induced oxidative muscle fiber-related gene expression, and inhibited glycolytic fiber-related gene expression in C2C12 cells. Muscle mass, the percentage of slow oxidative fibers, succinic dehydrogenase activity, muscle endurance, glucose tolerance, and the expression of the MyHC1 and MyHC2a genes increased while MyHC2b expression, lactate dehydrogenase activity, and the percentage of glycolytic muscle fibers decreased in SDSS-treated mice. Mechanistically, SDSS bound to the pyruvate kinase PKM1 and significantly repressed its activity. PKM1 inhibited MyHC1 and MyHC2a expression but promoted MyHC2b expression. SDSS also significantly attenuated the effects of PKM1 on muscle fiber-related gene expression in C2C12 cells. Our findings indicate that SDSS promotes muscle fiber transformation from the glycolytic type to the oxidative type by inhibiting PKM1 activity, which provide a new idea for treating muscle atrophy, muscle metabolism diseases and improving animal meat production.
研究领域:
药理学
·
肌肉生物学
·
代谢疾病
·
分子生物学
·
细胞生物学
·
动物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Zewen Shi,Fang Yang,Qian Pang,Yiwei Hu,Haijian Wu,Xueqiang Yu,Xianjun Chen,Lin Shi,Bowen Wen,Rui Xu,Ruixia Hou,Dan Liu,Qingjiang Pang,Yabin Zhu
With the development of minimally invasive orthopedics, injectable materials for bone repair are attracted more attention, especially for those wound with a small external mouth and sizeable internal cavity. In this work, the hydrogel with features of thermo-responsiveness, degradability and injectability was designed and fabricated. The hydrogel, named as FHCS, is composed of Pluronic F-127 (F127) loaded with carboxymethyl chitosan/sodium alginate nanoparticles (nCS) and nanohydroxyapatite (nHA). The hydrogel FHCS was non-toxic and good hemocompatible. It can enhance the ALP activity and extracellular matrix calcification of MC3T3-E1 due to the chitosan-based nanoparticle components (nCS). Moreover, FHCS-5 (containing 5 mg/mL nCS) showed relative high expression of osteogenic genes and protein markers. Osteal regeneration was observed treated by FHCS-5 hydrogel in a critical-size rat calvarial bone defect model. CT scanning showed that the whole defect was basically covered by new bone after FHCS-5 hydrogel. The results of H&E staining and Masson's trichrome staining on histological sections further confirmed that FHCS-5 hydrogel promoted new osteal formation and maturation, which up regulated the osteogenic related genes and proteins of ALP, OCN, OPN through BMP/Smad signaling pathway. Hence, this study suggests that FHCS-5 hydrogels have a promising application for non-loading bone regeneration.
研究领域:
生物医学工程
·
材料科学
·
骨科
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Yingping Zhang,Yue Wang,Lin Chen,Jun Zheng,Xiaojing Fan,Xinglian Xu,Guanghong Zhou,Niamat Ullah,Xianchao Feng
Great challenges remain in the effective control of irregular and incompressible deep wound bleeding and the promotion of wound healing after bacterial infection. In this study, cryogels were prepared using an ice template based on chitosan (CS), oxidized gallic acid (OGA) and hemin (HE), which are all green edible materials. The cryogels exhibit rapid blood-triggered shape recovery and a high swelling ratio. The cryogels with 5 mg mL −1 HE (Gel-CS/ [email protected] ) exert excellent photothermal effects. Additionally, the cryogels have excellent cytocompatibility and blood clotting abilities. In the mouse liver injury model and mouse tail amputation model, Gel-CS/ [email protected] presents better hemostasis properties than gauze and a gelatin sponge. Moreover, Gel-CS/ [email protected] displays excellent healing performance as a wound dressing. Overall, we provide a simple and effective strategy to prepare cryogels for controlling wound bleeding and promoting wound healing.
研究领域:
材料科学
·
生物材料
·
生物医学工程
·
止血
·
伤口愈合
·
抗菌材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Kunmei Xie,Feibiao Wang,Yue Yang,Shoujie Pan,Junyao Wang,Nan Xiao,Xinyan Wang,Zhihao Ma,Xiaolong Xu,Zibo Dong
Sepsis-associated acute liver injury (ALI) is a deadly condition resulting from a systemic inflammatory response to liver cell damage and malfunction. Monotropein (MON) belongs to the iris group of compounds extracted from the natural product Mollen dae officinalis radix, which has strong anti-inflammatory and antioxidant pharmacological effects. The purpose of this study was to elucidate the underlying mechanism of MON in the treatment of sepsis ALI. In this study, an in vivo caecal ligation puncture (CLP)-induced ALI model and in vitro LPS-stimulated AML12 cells and RAW264.7 cells model were established. Additionally, a variety of experimental techniques, including CCK8, H&E staining, DHE probe labelling, biochemical, QPCR, and Western blotting and blocking tests, were used to explore the role of MON in ALI. The results showed that MON improved liver morphological abnormalities, oedema, histopathological injury, and elevated ALT and AST, providing a protective effect against ALI. MON reduced CYP2E1 expression, alleviated oxidative stress (downregulation of MDA levels and upregulation of GSH, CAT, and T-AOC levels) and ROS accumulation with the involvement of the NRF2-Keap-1 pathway. MON inhibited inflammation via the TLR4/NF-κB/NLRP3 inflammasome pathway. In addition, it activated the Akt (Ser473)/GSK3β (Ser9)/Fyn pathway and accelerated NRF2 nuclear accumulation; MK-2206 blockade reversed the NRF2 nuclear accumulation and anti-inflammatory function of MON. MON also restricted the mitochondrial apoptosis pathway, a process specifically blocked by MK-2206. In summary, we concluded that MON alleviated septic ALI by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3β (Ser9)/Fyn/NRF2 pathway.
研究领域:
药理学
·
免疫学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2023
·
IF 3.9
Peng Huixin,Huang Yanxin,Wei Guangji,Pang Yanfang,Yuan Huixiong,Zou Xiong,Xie Yu’an,Chen Wencheng
Aluminum contamination is a growing environmental and public health concern, and aluminum testicular toxicity has been reported in male rats; however, the underlying mechanisms of this toxicity are unclear. The objective of this study was to investigate the effects of exposure to aluminum chloride (AlCl 3 ) on alterations in the levels of sex hormones (testosterone [T], luteinizing hormone [LH], and follicle-stimulating hormone [FSH]) and testicular damage. Additionally, the mechanisms of toxicity in the testes of AlCl 3 -exposed rats were analyzed by proteomics. Three different concentrations of AlCl 3 were administered to rats. The results demonstrated a decrease in T, LH, and FSH levels with increasing concentrations of AlCl 3 exposure. HE staining results revealed that the spermatogenic cells in the AlCl 3 -exposed rats were widened, disorganized, or absent, with increased severe tissue destruction at higher concentrations of AlCl 3 exposure. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses revealed that differentially expressed proteins (DEPs) after AlCl 3 exposure were primarily associated with various metabolic processes, sperm fibrous sheath, calcium-dependent protein binding, oxidative phosphorylation, and ribosomes. Subsequently, DEPs from each group were subjected to protein-protein interaction (PPI) analysis followed by the screening of interactional key DEPs. Western blot experiments validated the proteomics data, revealing the downregulation of sperm-related DEPs (AKAP4, ODF1, and OAZ3) and upregulation of regulatory ribosome-associated protein (UBA52) and mitochondrial ribosomal protein (MRPL32). These findings provide a basis for studying the mechanism of testicular toxicity due to AlCl 3 exposure.
研究领域:
毒理学
·
环境健康
·
生殖生物学
·
蛋白质组学
·
分子生物学
✓ 已验证
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）