RESPIRATORY RESEARCH
·
2024
·Vol. 25
·期 1
·1-20
·
IF 4.7
Lian Hui,Xu Kai,Chang Airu,Wang Yaxuan,Ma Shuaichen,Cheng Lianhui,Zhao Wenyu,Xia Cong,Wang Lan,Yu Guoying
Idiopathic pulmonary fibrosis (IPF) is a high-mortality lung disease with unclear pathogenesis. Convincing evidence suggests that an imbalance in mitochondrial homeostasis resulting from repeated injury to alveolar epithelial type 2 cells (AEC2) underlies IPF. Non-receptor protein tyrosine phosphatase 21 (PTPN21) performs various functions in cancer; however, its role in IPF has not been studied. This study aimed to investigate the role of PTPN21 in lung fibrosis. The experimental results showed that loss of PTPN21 exacerbated lung fibrosis by increasing cell numbers in bronchoalveolar lavage fluid, lung hydroxyproline content, and extracellular matrix protein expression of fibronectin and α-smooth muscle actin (α-SMA) in bleomycin-challenged mouse lungs. In A549 cells (AEC2), knockdown of PTPN21 suppressed focal adhesion and migration, reduced mitochondrial fission and increased fusion, increased the level of mitochondrial superoxide, decreased mitochondrial membrane potential and ATP levels. Simultaneously, knockdown of PTPN21 impaired autophagy, and increased intracellular reactive oxygen species levels. Treatment of fibroblasts (MRC-5) and primary human lung fibroblasts (PHLF)) with the supernatant from PTPN21-knockdown A549 cells increased the expression of fibronectin, collagen 1 and α-SMA. Conversely, overexpression of PTPN21 in A549 cells produced opposite effects. However, treatment of MRC-5 and PHLF with the supernatant from PTPN21-overexpressing A549 cells only slightly reduced the expression of fibronectin, collagen 1 in MRC-5 cells, but did not change the expression of α-SMA. In summary, this study revealed that the loss of PTPN21 in epithelial cells disrupted mitochondrial metabolic homeostasis, leading to epithelial cell inactivation and increased the deposition of extracellular matrix proteins in fibroblasts, thereby exacerbating experimental pulmonary fibrosis.
研究领域:
呼吸病学
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细胞生物学
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分子生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
·
IF 3.361
Chunyan Li,Xiao Sun,Ang Li,Min Mo,Zhongxi Zhao
Pulmonary fibrosis (PF) is a disease characterized by diffusing alveolar inflammation and alveolar structural disorders that ultimately lead to pulmonary interstitial fibrosis. S-allylmercaptocysteine (SAMC) as a water-soluble organosulfur garlic derivative exhibits efficient anti-inflammatory and anti-oxidative activities. In this study, we attempted to explore the function of SAMC in inhibiting bleomycin (BLM)-induced pulmonary fibrosis in mice. 0.035 U/g of BLM was intraperitoneally injected into mice twice per week for 4 weeks to induce fibrosis. SAMC (25 and 50 mg/kg) and N-acetylcysteine (NAC, 600 mg/kg) were given to mice for 28 days. The results indicate that SAMC could significantly ameliorate the pathological structure, and decrease inflammatory cell infiltration and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in BLM-induced pulmonary fibrosis mice. SAMC showed an anti-fibrosis effect by increasing anti-oxidants like HO-1, GSH and SOD as well as decreasing hydroxyproline (HYP) in BLM-induced mice. Mechanistic studies suggested that SAMC alleviated oxidative stress probably by impacting the Nox4/Nrf2 pathways, and played an anti-fibrosis role with decreasing the expression of α-SMA, collagen III, collagen I by suppressing the TGF-β1/Smad pathway. These findings indicate that SAMC may be partially responsible for the therapeutic effect on PF patients.
研究领域:
药理学
·
肺科学
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免疫学
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病理学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Wan-Ying Li,Jun-Yang Liu,Zi-Xian Wang,Ke-Ying Wang,Chun-Xiang Huang,Wen He,Jia-Le Song
Ulcerative colitis (UC) is a chronic gastrointestinal disease that results from repeated inflammation and serious complications. Sinapic acid (SA) is a hydroxycinnamic acid present in a variety of plants that has antioxidant, anti-inflammatory, anticancer, and other protective effects. This study investigated the antifibrotic effect of SA on chronic colitis induced by dextran sulfate sodium salt (DSS) in mice. We observed that SA could significantly reduce clinical symptoms (such as improved body weight loss, increased colon length, and decreased disease activity index score) and pathological changes in mice with chronic colitis. SA supplementation has been demonstrated to repair intestinal mucosal barrier function and maintain epithelial homeostasis by inhibiting activation of the NLRP3 inflammasome and decreasing the expression of IL-6, TNF-α, IL-17A, IL-18, and IL-1β. Furthermore, SA could induce the expression of antioxidant enzymes (Cat, Sod1, Sod2, Mgst1) by activating the Nrf2/keap1 pathway, thus improving antioxidant capacity. Additionally, SA could increase the protein expression of downstream LC3-II/LC3-I and Beclin1 and induce autophagy by regulating the AMPK-Akt/mTOR signaling pathway, thereby reducing the production of intestinal fibrosis-associated proteins Collagen-I and α-SMA. These findings suggest that SA can enhance intestinal antioxidant enzymes, reduce oxidative stress, expedite intestinal epithelial repair, and promote autophagy, thereby ameliorating DSS-induced colitis and intestinal fibrosis.
研究领域:
药理学
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胃肠病学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Zheng Chen,Zixuan Zhou,Xinyuan Zhang,Zhengyue Wang,Jinchen Fan,Wenyi Wang,Yongjun Zheng,Shige Wang
Facilitating swift burn wound healing while effectively preventing scar formation continues to be a considerable challenge in medical practice. In this study, an injectable carboxymethyl chitosan/oxidized dextran/polyvinylpyrrolidone/dopamine (COPD) hydrogel was designed for effective sequentially promotion of burn wound healing and inhibition of scar formation. The COPD hydrogel precursor solution was injected into the burn wound via a double-barreled syringe and transformed into an adherent hydrogel within 25 s. The inclusion of dopamine imparted good free radical scavenging properties to the hydrogel. In particular, the gradual oxidation of dopamine to polydopamine enabled a unique heat production pattern—initially slow (photothermal conversion efficiency: 30.3 %) and then rapidly temperature increasing (photothermal conversion efficiency: 42.8 %) —under a single laser irradiation. The effect of promoting healing at the initial stage of the wound was evaluated by constructing a male C57BL/6 mice model with deep second-degree burns, observation of the wound area, PCR analysis, and immunohistochemical staining. Furthermore, the scar inhibition was confirmed by observing reduced expression levels of α-SMA and COL I, along with a decreased collagen I/III ratio. With tunable mechanical properties (maximum compressive strength of 966.4 ± 51.7 kPa), the COPD hydrogel holds significant promise as an adjunctive photothermal platform for intelligent burn wound management.
研究领域:
生物医学工程
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材料科学
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伤口愈合
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光热疗法
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产品关联
DOI
PubMed
高影响因子
PULMONARY PHARMACOLOGY & THERAPEUTICS
·
2024
·
IF 3.3
Huijuan Zhang,Jianli Qiu,Qianyi Zhao,Yong Zhang,Haitao Zheng,Ziying Dou,Yongbin Yan
Pulmonary fibrosis is a complex disease that can occur in a variety of clinical settings. The Zinc Finger and BTB Domain Containing 16 (Zbtb16) is a transcription factor and has not been studied in pulmonary fibrosis. Lung tissues from rats which were treated with bleomycin and Tanshinone IIA (Tan IIA) were collected for mRNA sequencing. Zbtb16, a differentially expressed gene, was screened. Using adeno-associated virus to knock down Zbtb16 in rats, it was found that the lung index and the content of hydroxyproline in lung tissue were decreased. HE and Masson staining revealed that pathological symptoms of lung histopathology were relieved after Zbtb16 knockdown. Protein expressions of α-SMA, Collagen I and Fibronectin were significantly decreased after Zbtb16 knockdown in vivo and in vitro . Meanwhile, the protein content of TGF-β1 and the phosphorylation of Smad2/3 were inhibited by Zbtb16 knockdown. Conversely, under the treatment of Tan IIA and TGF-β1, overexpression of Zbtb16 improved cell viability, increased the expression of fibrosis-related proteins, and promoted the phosphorylation of Smad 2/3. All above demonstrates that Zbtb16 inhibition ameliorates pulmonary fibrosis and suppresses the TGF-β/Smad pathway. Furthermore, Zbtb16 mediates the inhibitory process of Tan IIA on pulmonary fibrosis. This study provides a novel candidate therapeutic target for pulmonary fibrosis.
研究领域:
药理学
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肺病学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
RSC Medicinal Chemistry
·
2024
·
IF 4.1
Jingsong Lu,Ying Li,Xiaohan Gao,Sumei Chen,Zeping Jin,Xiaoxaio Guo,Wensheng Xie,Zhenhu Guo,Yen Wei,Lingyun Zhao
A smart dendritic cells (DC)-derived whole cell cytokines (DWCs) nano-regulator of TCP was developed for tumor cytokine-immunotherapy. The DWCs were purified from activated DC-cultured mediums and applied as a nano-dosage form. It was found that TCP could remodel extracellular matrix via the elimination of fibronectin and type I collagen (Col-I) in tumor tissues, as well as the inhibition of α-SMA expression in cancer associated fibroblasts (CAF). Furthermore, after local TCP treatment, significant tumor inhibition could be achieved combined with radiotherapy.
研究领域:
癌症生物学
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免疫学
·
纳米技术
·
肿瘤微环境
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Xia Yuan,Rao Zilong,Wu Simin,Huang Jiayao,Zhou Haiyun,Li Hanzhao,Zheng Hui,Guo Daxin,Quan Daping,Ou Jing-Song,Bai Ying,Liu Yunqi
Coronary artery bypass grafting is acknowledged as a major clinical approach for treatment of severe coronary artery atherosclerotic heart disease. This procedure typically requires autologous small-diameter vascular grafts. However, the limited availability of the donor vessels and associated trauma during tissue harvest underscore the necessity for artificial arterial alternatives. Herein, decellularized bovine intercostal arteries were successfully fabricated with lengths ranging from 15 to 30 centimeters, which also closely match the inner diameters of human coronary arteries. These decellularized arterial grafts exhibited great promise following poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) grafting from the inner surface. Such surface modification endowed the decellularized arteries with superior mechanical strength, enhanced anticoagulant properties, and improved biocompatibility, compared to the decellularized bovine intercostal arteries alone, or even those decellularized grafts modified with both heparin and vascular endothelial growth factor (VEGF). After replacement of the carotid arteries in rabbits, all surface-modified vascular grafts have shown good patency within 30 days post-implantation. Notably, strong signal was observed after α-SMA immunofluorescence staining on the PMPC-grafted vessels, indicating significant potential for regenerating the vascular smooth muscle layer and thereby restoring full structures of the artery. Consequently, the decellularized bovine intercostal arteries surface modified by PMPC can emerge as a potent candidate for small-diameter artificial blood vessels, and have shown great promise to serve as viable substitutes of arterial autografts.
研究领域:
生物材料
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组织工程
·
血管外科
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2020
·
IF 3.723
Yu Miao,Yanling Wu,Yingjin Jin,Mengze Lei,Jixing Nan,Xue Wu
Liver fibrosis is a common pathological consequence of liver injury, which increases liver failure-related morbidity and mortality. Hence, anti-fibrotic treatment is urgently needed. Oxidative stress plays a pivotal role in the progression of liver fibrosis. Thus, targeting ROS may be an effective strategy for liver fibrosis treatment. In this study, we investigated four benzoquinones derivatives, including 5-isopropyl-2-methyl-1,4-benzoquinone (TQ), 2-tert-butyl-1,4-benzoquinone ( t Bu-Q) 2,5-dimethyl-p-benzoquinone (Dime-Q) and p-benzoquinone (Ph-Q), as well as the evaluation of their antioxidant activity and anti-fibrotic effects on activated hepatic stellate cells and TAA-induced mice. Electrochemical analysis showed that all compounds possessed antioxidant property. The result was first confirmed by in vitro experiments, which revealed potential anti-fibrotic activity of all four compounds at the cellular level. Benzoquinone derivatives act as ROS-scavenging molecules, which modulated the TLR4-CD14 signaling pathway to inhibit the expression of procaspase-1 and IL-1β in cells, induced apoptosis via a mitochondrial pathway by upregulating the ratio of Bax/Bcl-2 and by activating caspase-3, as well as inhibited the expression of the anti-apoptotic proteins FLIP and XIAP in activated LX-2 cells. In addition, a TAA (Thioacetamide)-induced mouse model was used to further validate the results. Treatment with benzoquinone derivatives significantly decreased the levels of liver injury markers and lipid peroxidation caused by excessive ROS, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA). Moreover, treatment with benzoquinone derivatives significantly inhibited extracellular matrix (ECM) deposition and downregulated the mRNA and protein expression of liver fibrosis markers, such as collagen I, alpha-smooth muscle actin (α-SMA), and TIMP-1. In summary, these results indicate that benzoquinone derivatives may act as potential therapeutic drugs against liver fibrosis.
研究领域:
药理学
·
肝病学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Lanlan Zong,Runxin Teng,Huiqi Zhang,Wenshang Liu,Yu Feng,Zhengmao Lu,Yuxiao Zhou,Zhen Fan,Meng Li,Xiaohui Pu
Despite advancements in therapeutic agents for diabetic chronic wounds, challenges such as suboptimal bioavailability, intricate disease milieus, and inadequate delivery efficacy have impeded treatment outcomes. Here, ultrasound-responsive hydrogel incorporated with heparin-binding domain (HBD) peptide nanoparticles is developed to promote diabetic wound healing. HBD peptide, derived from von Willebrand Factor with angiogenic activity, are first engineered to self-assemble into nanoparticles with enhanced biostability and bioavailability. Ultrasound responsive cargo release and hydrogel collapses are first verified through breakage of crosslinking. In addition, desired antioxidant and antibacterial activity of such hydrogel is observed. Moreover, the degradation of hydrogel under ultrasound stimulation into smaller fragments facilitated the deeper wound penetration of ≈400 µm depth. Complete wound closure is observed from diabetic mice with chronic wounds after being treated with the proposed hydrogel. In detail, in vivo studies revealed that hydrogels loaded with HBD peptide nanoparticles increased the levels of angiogenesis-related growth factors (VEGF-A, CD31, and α-SMA) to effectively accelerate wound repair. Overall, this study demonstrates that ultrasound-responsive HBD peptide hydrogel provides a synergistic therapeutic strategy for external biofilm elimination and internal effective delivery for diabetic wounds with biofilm infection.
研究领域:
生物医学工程
·
药学
·
伤口愈合
·
纳米技术
·
生物材料
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
·
2018
·Vol. 29
·期 9
·1-11
·
IF 2.448
Hong Lei,Shen Meiting,Fang Jiaxi,Wang Yezhao,Bao Zhiyuan,Bu Shizhong,Zhu Yabin
In this work, two kinds of hyaluronic acid (HA)-based hydrogels were fabricated: one is made from physical freezing-thawing of HA solution (HA1), and the other is from chemical cross-linking of HA and polysaccharide (HA2). They were applied to repair full-thickness skin defects with New Zealand rabbits as the test animals, using powder HA and cotton dress as the references. The wound starts to heal after wounds were disinfected with iodine followed by coating with HA2, HA1, HA and cotton dress (the control), respectively. They were recorded as 4 treatments (groups), HA2, HA1, HA and the control. The healing progress was followed and tested in the duration of 56 days, and the biological repairing mechanism was explored. From the wound area alteration, white blood cell (WBC) measurements and H&E staining, HA2 was the most promising treatment in promoting the wound healing with least serious scar formation. Immunochemistry analyses and real-time PCR tests of the bio-factors involved in the wound healing, vascular endothelial growth factor (VEGF), alpha-smooth muscle actin (α-SMA) and transforming growth factor beta-1 (TGF-β1), exhibited that HA2 enhanced VEGF and α-SMA secretion but reduced TGF-β1 expression at early stage, which alleviated the wound inflammation, improved the skin regeneration and relieved the scar formation.
研究领域:
生物材料
·
伤口愈合
·
组织工程
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Lei Lei,Guoguo Wan,Xiaoyu Geng,Jianguo Sun,Yi Zhang,Jianwei Wang,Congwen Yang,Zheng Pan
Ethnopharmacological relevance Lamiophlomis rotata (Benth.) Kudo ( L . rotata ), a Tibetan medicinal plant , is used to treat “yellow-water diseases”, such as skin disease, jaundice and rheumatism . Our previous study showed that the iridoid glycoside extract of L. rotata (IGLR) is the major constituent of skin wound healing. However, the role of IGLR in the biological process of trauma repair and the probable mechanism of the action remain largely unknown. Aim of the study To investigate the role of IGLR in the biological process of trauma repair and the probable mechanism of the action. Materials and methods The role of IGLR in wound healing was investigated by overall skin wound in mice with Hematoxylin and Eosin (H&E) and Masson trichrome staining. The anti-inflammatory, angiogenesis-promoting and fibril formation effects of IGLR were visualized in wound skin tissue by immunofluorescence staining, and the proinflammatory factors and growth factors were assayed by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Macrophages, dermal fibroblasts, and endothelial cells were cultured to measure the direct/indirect interaction effects of IGLR on the proliferation and migration of cells, and flow cytometry was employed to assess the role of IGLR on macrophage phenotype. Network pharmacology combined with Western blot experiments were conducted to explore possible mechanisms of the actions. Results IGLR increased the expression of CD206 (M2 markers) through the RAS/p38 MAPK/NF-κB signaling pathway during wound injury in vivo and in vitro . IGLR suppressed the inflammatory cytokines iNOS, IL-1β and TNF-α in the early stage of wound healing . During the proliferation step of wound repair, IGLR promoted angiogenesis and fibril formation by increasing the expression of VEGF, CD31, TGF-β and α-SMA in wound tissue, and similar results were verified by RT-PCR and ELISA. In a paracrine mechanism, the extract promoted the proliferation of dermal fibroblasts, and endothelial cells were founded by the conditioned medium (CM). Conclusion IGLR induced M2 macrophage polarization in the early stage of wound healing; in turn, IGLR played a key role in the transition from inflammation to cell proliferation during the biological process of wound healing.
研究领域:
药理学
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免疫学
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伤口愈合
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植物科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOLOGY REPORTS
·
2024
·Vol. 51
·期 1
·1-10
·
IF 2.6
Li Zhipeng,Jiao Yang,Wu Zhisong,Liu Haoge,Li Yang,Cai Yaodong,Wei Wan,Cao Fang
Background Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by a constant incidence rate. Unfortunately, effective pharmacological treatments for this condition are lacking and the identification of novel therapeutic approaches and underlying pathological mechanisms are required. This study investigated the potential of quercetin in alleviating pulmonary fibrosis by promoting autophagy and activation of the SIRT1/AMPK pathway. Methods Mouse models of IPF were divided into four treatment groups: control, bleomycin (BLM), quercetin (Q), and quercetin + EX-527 (Q + E) treatment. Pulmonary fibrosis was induced in the mouse models through intratracheal instillation of BLM. Various indexes were identified through histological staining, Western blotting analysis, enzyme-linked immunosorbent assay, immunohistochemistry, and transmission electron microscopy. Results Quercetin treatment ameliorated the pathology of BLM-induced pulmonary fibrosis of mice by reducing α-smooth muscle actin (α-SMA), collagen I (Col I), and collagen III (Col III) levels, and also improved the level of E-cadherin in lung tissue. Furthermore, Quercetin significantly enhanced LC3II/LC3I levels, decreased P62 expression, and increased the number of autophagosomes in lung tissue. These effects were accompanied by the activation of the SIRT1/AMPK pathway. Treatment with EX-527, an inhibitor for SIRT1, reversed all effects induced by quercetin. Conclusion This study showed that quercetin could alleviate pulmonary fibrosis and improve epithelial-mesenchymal transition by acting on the SIRT1/AMPK signaling pathway, which may be achieved by regulating the level of autophagy.
研究领域:
药理学
·
病理学
·
分子生物学
·
细胞生物学
✓ 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）