INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Jianfa Wu,Lingli Jiang,Sihong Wang,Lei Peng,Rong Zhang,Zhou Liu
The involvement of Interferon-stimulated exonuclease gene 20 (ISG20) has been reported in renal clear cell carcinoma, hepatocellular carcinoma, and cervical cancer. However, its role in ovarian cancer chemotherapy remains unclear. In this study, we conducted a comparative analysis of TGF-β1 and ISG20 in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells and tissues using qRT-PCR and a tissue immunofluorescence analysis. We also investigated the impact of ISG20-targeted drugs (IFN-γ) and TGF-β1 inhibitors on cisplatin response both in vivo and in vitro. Additionally, we assessed the effects of TGF-β1 or ISG20 on the polarization of tumor-associated macrophages through flow cytometry and ELISA analysis. Our findings revealed that ISG20 expression was lower in cisplatin-resistant tissues compared to cisplatin-sensitive tissues; however, overexpression of ISG20 sensitized ovarian cancer to cisplatin treatment. Furthermore, activation of ISG20 expression with IFN-γ or TGF-β1 inhibitors enhanced the sensitivity of ovarian cancer cells to cisplatin therapy. Notably, our results demonstrated that TGF-β1 promoted M2-type macrophage polarization as well as PI3K/mTOR pathway activation by suppressing ISG20 expression both in vivo and in vitro. In conclusion, our study highlights the critical role played by ISG20 within the network underlying cisplatin resistance in ovarian cancer. Targeting ISG20 using IFN-γ or TGF-β1 inhibitors may represent a promising therapeutic strategy for treating ovarian cancer.
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PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 48
·2105084
·
IF 18.808
Yiting Lei,Yuping Wang,Jieliang Shen,Zhengwei Cai,Yongsheng Zeng,Piao Zhao,Junyi Liao,Chengjie Lian,Ning Hu,Xiaoji Luo,Wenguo Cui,Wei Huang
The differentiation potentials and viability of stem cells are often impaired during cell isolation and delivery. Inspired by the phenomenon where islands can recruit seabirds for nesting, “cell island” microgels (MGs), that is, growth factor-loaded methacrylated hyaluronic acid and heparin blend MGs, which can recruit endogenous stem cells and promote chondrogenic differentiation, are constructed using microfluidic technology and photopolymerization processes, followed by non-covalently binding platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta3 (TGF-β3). The loading efficiency of PDGF-BB and TGF-β3 are 96% and 91%, respectively. In vitro and in vivo experiments find that the “cell island” MGs can enhance the migratory capacity of cells and recruit them from their niche via releasing PDGF-BB. Meanwhile, by using hyaluronic acid, the “cell island” MGs provide a suitable microenvironment for cell attachment and spreading. Furthermore, the “cell island” MGs induce chondrogenic differentiation of the recruited cells via releasing TGF-β3 and present a promising therapeutic effect for osteoarthritis. In sum, this developed “cell island” MG might serve as a temporary “nest site” to allow the migration, adhesion, and differentiation of endogenous stem cells, which can be a promising candidate rather than the conventional cell-seeded scaffolds for promoting tissue regeneration.
研究领域:
生物医学工程
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组织工程
·
再生医学
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Hua Han,Lu Liu,Jieping Zhang,Meng Zhang,Xinyu Chen,Yuyuan Huang,Wenxiu Ma,Huanlong Qin,Li Shen,Jundong Zhang,Wensheng Yang
Inflammatory bowel disease (IBD), a progressive and unpredictable colorectal inflammatory disease, is a global health problem. Currently, therapeutic strategies for the management of the disease are limited. Results from our previous studies indicated that probiotic Lactobacillus plantarum exhibits therapeutic effects against IBD, and through screening, we obtained an active 61-amino-acid long protein, L. plantarum membrane protein 1 (LpMP-1). Based on druggability-guided strategies, the search for LpMPs with lower molecular weights and better bioactivities contributes to the development of new anti-inflammatory agents to overcome the limitations of existing therapies against IBD. We used amino-acid-truncation strategies to obtain modified LpMPs (LpMP-2 - LpMP-9) using LpMP-1 as the parent template. Furthermore, we systematically evaluated the anti-colitis pharmacodynamics of these LpMPs in terms of symptomatology, histopathology, and cytokine levels in DSS-induced ulcerative colitis mice. Their possible targets of action against IBD was investigated under an iTRAQ-based pharmacoproteomic system and a docking-guided receptor-ligand relationship frame. We found a new active protein, LpMP-8, which had a lower molecular weight than LpMP-1. LpMP-8 was found to exhibit anti-colitis activity following oral administration in vivo (50 μg/kg) by improving symptoms of colitis, colonic ulcerations, and cytokine disorders. TLRs and TGF-β were found to be involved in the action of LpMP-8 against colitis; LpMP-8 was to compete with TLR4-MD2-bound LPS and reverse TGF-β and Smad2/7 disorders. Our probiotic-derived LpMP-8 was shown to elicit oral anti-colitis activity, and its significant efficacy is probably associated with TLR4 and TGF-β.
研究领域:
胃肠病学
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药理学
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微生物学
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免疫学
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PubMed
高影响因子
Nano Research
·
2022
·Vol. 15
·期 9
·8214-8227
·
IF 10.269
Ding Yifan,Wang Huan,Wang Yunyun,Li Long,Ding Jiahui,Yuan Caiyan,Xu Tao,Xu Haoran,Xie Hui,Zhu Ning,Hu Xin,Fang Huang,Tan Songwei
Intervertebral disc degeneration (IDD) is closely related to inflammation and imbalance of synthesis/catabolism of extracellular matrix (ECM) in intervertebral disc (IVD). Considering this, luteolin (LUT), a kind of natural flavonoid with good anti-inflammatory effect and TGF-β1 (a gene that promotes the regeneration of ECM) plasmid was co-loaded and co-delivered to nucleus pulposus cells (NPCs). Reactive oxygen species (ROS) responsive cationic copolymer, poly(β-amino ester)-poly(ε-caprolactone) (PBC), with high plasmid DNA (pDNA) compression affinity was synthesized. It can self-assemble into nano-sized polyplexes (pDNA@PBC) with virus-inspired structure and function through which it can transfect pDNA into NPCs with very high efficiency and negligible cytotoxicity. LUT was encapsulated in the hydrophobic core of pDNA@PBC. The co-delivery system, LUT-pTGF-β1@PBC, could enhance the cellular uptake of NPCs and manifest excellent sustained drug release in IVD. Real time quantitative polymerase chain reaction (RT-qPCR) and Western blot experiments reveal that the co-delivery system could inhibit inflammation in NPCs and restore the balance of anabolism and catabolism in vitro by activating TGF/SMAD3 and inhibiting NF- k B/p65. Moreover, LUT-pTGF-β1@PBC retards IDD in vivo as detected by radiological and histological methods with good biosafety in rats. LUT-pTGF-β1@PBC may be a promising option for the treatment of IDD.
研究领域:
生物医学工程
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药学
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骨科
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纳米技术
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DOI
高影响因子
Advanced Science
·
2026
·
IF 14.1
Peng Dai,Jikuang Zhao,Chang Xue,Kailei Xu,Liang Yong,Zhuangwei Zhang,Yi Huang,Jianwei Shuai,Xianzhen Chen,Sheng Nie,Junpeng Xu
Parkinson's disease (PD) is characterized by progressive dopaminergic neuron loss compounded by oxidative stress and neuroinflammation within a self‐perpetuating pathological brain microenvironment. Here, we report a bioactive injectable self‐healing hydrogel (COPRP) constructed by crosslinking oxidized Polygonati rhizoma polysaccharide (OPRP) with carboxymethyl chitosan via dynamic Schiff base linkages. OPRP is structurally identified as an inulin neoseries‐type fructan with relevance to TGF‐β/Smad pathway regulation. Without levodopa loading, COPRP reduced ROS accumulation and M1‐associated inflammatory markers in LPS‐stimulated microglia. It also improved cell viability, preserved mitochondrial membrane potential, and maintained TH expression in 6‐OHDA‐challenged SH‐SY5Y cells, supporting the intrinsic bioactivity of the hydrogel matrix. In a 6‐OHDA rat PD model, COPRP significantly ameliorated motor deficits and preserved TH‐positive neurons. Incorporating levodopa into COPRP creates a dual‐mechanism platform combining active microenvironmental remodeling with passive dopaminergic supplementation. Proteomic analysis, corroborated by western blotting, identified the TGF‐β/Smad signaling axis as the principal mechanistic mediator. Pharmacological intervention with pirfenidone attenuated TGF‐β2/Smad2/3 activation and partially reduced the behavioral and neuroprotective effects associated with COPRP, supporting the functional involvement of this pathway. This work delineates how a defined polysaccharide structure modulates the intracranial pathological microenvironment, offering insights for the rational design of bioactive biomaterials targeting neurodegenerative disease. An injectable, self‐healing COPRP hydrogel integrates structurally defined oxidized Polygonati rhizoma polysaccharide with carboxymethyl chitosan through dynamic Schiff‐base crosslinking. The bioactive matrix scavenges reactive oxygen species, suppresses neuroinflammation, protects dopaminergic neurons, and supports sustained levodopa release. Its therapeutic effects involve functional activation of TGF‐β2/Smad2/3 signaling within the Parkinsonian brain microenvironment. This design couples intrinsic biomaterial activity with complementary dopaminergic supplementation.
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高影响因子
APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Yi Wang,Linhao Hou,Yiqian Huang,Pengfei Wei,Liya Sun,Yan Zhang,Xueqiao Yu,Shiqing Ma,Wei Jing,Bo Zhao,Huachong Ma
Chronic wounds in diabetes take a lifetime risk of developing into diabetic foot ulcers (DFUs). Conventional wound dressings and commercial products fail for ideal tissue regeneration in DFUs due to the incapacity to promote vascularization and prevent bacterial infections during wound repair. In this study, the small intestinal submucosa (SIS) with enriched vascularized bioactive factors, was chemically decorated by 2-methacryloyloxy ethyl phosphorylcholine (MPC) through Michael-type addition to be endowed anti-fouling ability, in order to treat chronic wound regeneration in diabetes. In the diabetic skin injury experiment, we established the animal model by 5-mm diameter defects in the SD rats and implanted the bio-patches to the located sites. The SIS-MPC bio-patch showed superior advantages in bacterial anti-adhesion (100-fold foul resistance than commercial patches), while maintained affinity for fibroblast growth and collagen formation, as demonstrated by immunohistochemical staining from the local tissues, outperforming commercial wound dressings in tissue regeneration, which was attributed to acceleration in neovascularization and inflammation modulation through TGF-β and MAPK pathway. This novel SIS-MPC bio-patch would be a promising candidate for medical translations into diabetes and chronic wound treatments.
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高影响因子
AQUACULTURE
·
2022
·
IF 5.135
Hua Rong,Haoran Zhang,Lijun Ning,Kun Wu,Samwel Mchele Limbu,Qingchao Shi,Chuanjie Qin,Xiaobo Wen
The swim bladder performs various functions in fish, is consumed by humans and can be processed into high-grade fish glue (traditional high-value tonic). However, little is known on the optimum amount of proline (Pro) required for promoting collagen synthesis and deposition in fish swim bladder and the regulatory mechanism. This study explored the effects and optimum amount of dietary Pro supplementation on collagen synthesis and deposition in Chu's croaker ( Nibea coibor ) swim bladder and its possible molecular mechanism. A total of 450 juvenile fish (8.64 ± 0.14 g) were randomly stocked into 18 cages (25 fish per cage) in triplicate and fed Pro supplemented diets (0, 5, 10, 15, 20 and 25 g kg −1 ) for eight weeks. Another 225 fish (11.62 ± 0.15 g) were distributed randomly into control, Pro and Pro diet plus injected with specific inhibitor of Smad3 (SIS3) in order to inhibit the transforming growth factor beta (TGF-β)/Smads pathway. Pro supplementation up-regulated significantly the expression of genes involved in TGF-β/Smads pathway such as collagen, type I, alpha 1 ( col1a1 ) and 2 ( col1a2 ), TGF-β and Smad2/3 , and increased collagen content in the Chu's croaker swim bladder ( P < 0.05). The optimum dietary Pro supplementation for deposition of collagen in Chu's croaker swim bladder was 19.36 g kg −1 . The collagen content in the swim bladder positively correlated significantly with the mRNA expression of col1a1 , col1a2 , TGF-β and Smad2/3 genes ( P < 0.05). The optimum dietary Pro supplementation for maximum synthesis of collagen in Chu's croaker swim bladder was 13.25, 13.32 and 15.94 g kg −1 based on mRNA expression of Smads2 , Smads3 and col1a2 genes, respectively. SIS3 down-regulated the expression of col1a1 , col1a2 , TGF-β and Smad2/3 genes, subsequently decreased collagen deposition in the swim bladder ( P < 0.05). These results suggest that 13.25 to 19.36 g kg −1 Pro supplementation improve collagen synthesis and deposition in Chu's croaker swim bladder. The TGF-β/Smad signaling pathway regulates collagen synthesis and deposition in Chu's croaker swim bladder. Our results provide an understanding on the molecular mechanism of collagen synthesis and deposition in fish for producing collagen required for human food and fish glue.
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高影响因子
TOXICOLOGY LETTERS
·
2022
·
IF 4.271
Shuhong Guan,Hui Liu,Jun Zhou,Qiudi Zhang,Hui Bi
Transforming growth factor (TGF)-β1-induced fibrotic changes in alveolar epithelium is a critical event in pulmonary fibrosis . Herein, we recognized that lncRNA mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) was abnormally upregulated within human idiopathic pulmonary fibrosis (IPF) lung tissue, bleomycin (BLM)-caused pulmonary fibrotic model mice and TGF-β1-stimulated mice type II alveolar epithelial cells. In vivo , MIR100HG knockdown attenuated BLM-caused lung fibrogenesis in mice; in vitro , MIR100HG knockdown attenuated TGF-β1-induced fibrotic changes in mice type II alveolar epithelial cells. Through direct binding, MIR100HG knockdown upregulated microRNA-29a-3p (miR-29a-3p) expression; through serving as competing endogenous RNA for miR-29a-3p, MIR100HG knockdown downregulated TGF-beta activated kinase 1/MAP3K7 binding protein 1 (Tab1) expression. Finally, under TGF-β1 stimulation, Tab1 knockdown attenuated TGF-β1-induced fibrotic changes and partially attenuated the effects of miR-29a-3p inhibition. In conclusion, we demonstrated the aberrant upregulation of lncRNA MIR100HG in BLM-caused lung fibrogenesis and TGF-β1-stimulated MLE 12 cells. The MIR100HG/miR-29a-3p/Tab1 axis could modulate TGF-β1-induced fibrotic changes in type II alveolar epithelial cells and, thus, might be promising targets for pulmonary fibrosis therapy.
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PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 22
·7669
·
IF 4.6
Hongxing Zheng,Yingjun Hu,Mengli Shao,Simin Chen,Shanshan Qi
Chromium picolinate (CP) is an organic compound that has long been used to treat diabetes. Our previous studies found CP could relieve diabetic nephropathy. Thus, we speculate that it might have a positive effect on diabetic testicular injury. In this study, a diabetic rat model was established, and then the rats were treated with CP for 8 weeks. We found that the levels of blood glucose, food, and water intake were reduced, and body weight was enhanced in diabetic rats after CP supplementation. Meanwhile, in CP treatment groups, the levels of male hormone and sperm parameters were improved, the pathological structure of the testicular tissue was repaired, and testicular fibrosis was inhibited. In addition, CP reduced the levels of serum inflammatory cytokines, and decreased oxidative stress and apoptosis in the testicular tissue. In conclusion, CP could ameliorate testicular damage in diabetic rats, as well as being a potential testicle-protective nutrient in the future to prevent the testicular damage caused by diabetes.
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PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2023
·
IF 5.4
Ping Ping,Shasha Guan,Chaoxue Ning,Ting Yang,Yali Zhao,Pei Zhang,Zhitao Gao,Shihui Fu
Acute myocardial infarction (AMI) is a common cardiovascular condition that progressively results in heart failure. In the present study, we have designed to load transforming growth factor beta 3 (TGF-β3) and cardio potential exosomes into the blended polycaprolactone/type I collagen (PCL/COL-1) nanofibrous patch (Exo@TGF-β3@NFs) and examined its feasibility for cardiac repair . The bioactivity of the developed NFs towards the migration and proliferation of human umbilical vein endothelial cells was determined using in vitro cell compatibility assays. Additionally, Exo@TGF-β3/NFs showed up-regulation of genes involved in angiogenesis and mesenchymal differentiations in vitro . The in vivo experiments performed 4 weeks after transplantation showed that the Exo@TGF-β3@NFs had a higher LV ejection fraction and fraction shortening functions. Subsequently, it has been determined that Exo@TGF-β3@NFs significantly reduced AMI size and fibrosis and increased scar thickness. The developed NFs approach will become a useful therapeutic approach for the treatment of AMI.
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PubMed
高影响因子
Journal of Functional Foods
·
2020
·
IF 3.701
Shan Shan Qi,Meng Li Shao,Sun Ze,Hong Xing Zheng
Salidroside from Rhodiola rosea L. has hypoglycemic effects, and has anti-osteoporosis effect in diabetic rats. Whether it has beneficial effects on diabetic nephropathy (DN) has not been fully reported. Here, a DN rat model was established by streptozotocin (STZ). Salidroside (10, and 20 mg kg −1 d −1 ) were orally giving for eight weeks. The purity of salidroside was 99%. The results showed that eight weeks salidroside supplementation dose-dependently decreased blood glucose, serum insulin, serum creatinine, blood urea nitrogen (BUN), as well as urinary albumin of DN rats, repaired the pathological changes of kidney tissue, the renal sclerosis and fibrosis in the kidney of DN rats were improved, and the activities of oxidative defense system associated enzyme such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were also improved. Serum inflammatory cytokines (including tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, and interleukin-6) were decreased significantly in DN rats after eight weeks salidroside supplementation. Immunohistochemical results showed that fibrosis related proteins such as transforming growth factor-β1 (TGF-β1), phospho-Smad2 (p-Smad2), and phospho-Smad3 (p-Smad3) expression levels were decreased significantly in the kidney of salidroside treated group. Our results indicate that daily salidroside consumption could alleviate DN in rats, the main mechanisms are anti-inflammatory, anti-oxidative stress, and inhibition of the TGF-β1/Smad2/3 pathway. This study suggested that salidroside could be used as a nutrient against DN, as well as diabetes.
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高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Fujing Wang,Rong Hu,Jiaxing Zhang,Tingting Pei,Zhuo'en He,Liliang Ju,Zhongxiao Han,Mingqing Wang,Wei Xiao
Renal fibrosis is the pathological consequence of progressive chronic kidney disease . Although it has been reported that vitamin D3 exerts antifibrotic effects, the underlying mechanisms remain unclear. This study is aimed at investigating the effects and molecular mechanisms in high-dose vitamin D3 treatment on renal fibrosis. A model of chronic kidney disease was established by 5/6 nephrectomy in rats characterised by high levels of serum creatine, urea nitrogen, and urinary protein. Serum 25-dihydroxyvitamin D3, calcium and parathormone levels were measured to evaluate vitamin D levels. Hematoxylin and eosin , periodic acid Schiff and Mallory's Trichrome staining were used to evaluate histopathological changes in rats. Moreover, the expression of vimentin , collagen I, α-smooth muscle actin and E-cadherin were analyzed at molecular and histopathological levels. Our results showed that exposure to vitamin D3 decreased the levels of serum creatine, urea nitrogen and urine protein and restored the homeostasis of calcium and parathormone. Vitamin D3 also downregulated the expression of vimentin, collagen I and α-smooth muscle actin and attenuated renal fibrosis and epithelial to mesenchymal transition in the kidney. Importantly, vitamin D3 treatment increased the expression of the vitamin D receptor and inhibited Transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway in rats kidneys with chronic kidney disease. Mechanistically, the upregulation of TGF-β1 and phosphorylation of Smad3 induced by vitamin D3 was reversed by activation of the vitamin D receptor. Our findings indicated that vitamin D3 is a potential antifibrotic drug in chronic kidney disease via the vitmin D receptor and inhibiting TGF-β1/Smad3 signaling pathway.
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PubMed
高影响因子
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