JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 7
·956-968
·
IF 2.571
Wang Youpeng,Jing Weichao,Qu Wanying,Liu Zhiwei,Zhang Di,Qi Xiaoyu,Liu Lujia
ObjectivesThe aim of this study was to evaluate the effect of tectorigenin on treating allergic asthma model of guinea pigs and investigate the underlying mechanisms.MethodsAllergic asthma model of guinea pigs was established by sensitizing with ovalbumin (OVA). Then OVA-sensitized guinea pigs were injected with 10 mg/kg tectorigenin, 25 mg/kg tectorigenin or dexamethasone to investigate the effect of tectorigenin.Key findingsHigh dose of tectorigenin effectively decreased the number of coughs, the number of inflammatory cells and the levels of pro-inflammatory factors. Moreover, tectorigenin could inhibit pulmonary fibrosis in guinea pigs sensitized with OVA. In addition, the functions of tectorigenin were realized through downregulating profibrotic factors of transforming growth factor (TGF)-β1, phosphorylated (p)-Smad2/3 and Smad4, upregulating fibrosis-inhibitor of Smad7 and decreasing pro-inflammatory factors of vascular endothelial growth factor A (VEGFA), tumour necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-inhibitor of nuclear factor-kappa B (NF-κB) kinase β (p-IKKβ) and NF-κB.ConclusionsTectorigenin could inhibit pulmonary fibrosis and airway inflammation through TGF-β1/Smad signalling pathway and TLR4/NF-κB signalling pathway. Therefore, tectorigenin might be a promising medicine to treat allergic asthma.
研究领域:
药理学
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免疫学
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呼吸医学
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DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
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2025
·
IF 2.5
Yi Yang,Bei Tian,Xinyu Tian,Linyan Yao,Jianxi Xiao
Excessive ultraviolet radiation is one of the most common external factors causing skin photoaging, which leads to collagen degradation, wrinkle formation, pigmentation, and is even associated with skin disorders such as seborrheic keratosis and skin tumors. Although various strategies have been developed to treat photoaging skin; however, they suffer from poor stability, risk of allergic reactions, and prolonged recovery periods. In this study, we develop a novel highly stable and bioactive yak type I collagen-based hydrogels dressing to promote the rejuvenation of photoaged skin. The YIC gel demonstrated excellent stability over a six-month period, and maintained the intact triple-helical structure of collagen. It also displayed shear-thinning behavior and notable ductility. In vitro cell experiments confirmed its favorable biocompatibility and bioactivity.Non-invasive Combo evaluations demonstrated the remarkable ability of YIC gel to restore dermal density, elasticity, hydration, and transepidermal water loss to healthy levels, surpassing the efficacy of the commercial product. Histological analysis revealed YIC gel significantly reduced epidermal thickness, promoted the deposition and regeneration of collagen, demonstrating greater efficacy than the commercial product. Antioxidant indicators further highlighted the antioxidant properties of YIC gel, including reduced MDA content, increased SOD activity and GSH content. Immunofluorescence staining suggested that the YIC gel may enhance collagen synthesis through modulation of the TGF-β/Smad signaling pathway. This YIC gel offers valuable insights into its protective effects against skin photoaging and highlights its promising applications in cosmetic formulations.
研究领域:
生物材料
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皮肤科学
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生物医学工程
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化妆品科学
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分子生物学
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DOI
高影响因子
Biomaterials Advances
·
2022
·
IF 0
Ting Dai,Jiayi Ma,Su Ni,Chun Liu,Yan Wang,Siyu Wu,Jun Liu,Yiping Weng,Dong Zhou,Ana Jimenez-Franco,Hongbin Zhao,Xiubo Zhao
Electrospun PCL scaffolds have been widely used for tissue engineering as they have shown great potential to mimic the structure of the natural extracellular matrix (ECM). However, the small pore size and low bioactivity of the scaffolds limit cell migration and tissue formation. In this study, PCL (polycaprolactone), PCL/PEG (polyethylene glycol), and PCL/PEG/ATP (nano-attapulgite) scaffolds were fabricated via electrospinning. To increase the porosity of the scaffolds, they were washed to remove water-soluble PEG fibers. Then the porous structure was measured using scanning electron microscopy (SEM) and atomic force microscopy (AFM), which showed an increased porosity when PEG fibers were removed in PCL/PEG and PCL/PEG/ATP scaffolds. Moreover, the mechanical properties were also analyzed in dry and wet conditions. In vitro mouse multipotent mesenchymal precursor cells were used to assess the biocompatibility of the scaffolds, and osteogenesis was analyzed using CCK-8 and real-time PCR (RT-PCR) methods. Moreover, in vivo μCT, histological and immunohistochemical analyses were conducted to evaluate new bone formation in rat cranium defect models. Washed PCL/PEG/ATP scaffolds were implanted into the cranium defects in rats for 4 or 8 weeks, better cell infiltration was observed in these scaffolds than in unwashed ones. The result demonstrated that washed PCL/PEG/ATP scaffold facilitated the differentiation of MSCs into osteoblasts compared with PCL scaffold, as proved by the increased expression of osteogenic key genes as well as Smad1, Smad4, and Smad5. Furthermore, in vivo studies demonstrated that using the ATP-doped electrospun PCL scaffold can improve the bone regeneration of rat cranium defects. Particularly, the PCL/ATP-30% scaffold has the best effect compared to the other scaffolds. The enhanced osteogenesis and bone repair were related to the PCL/ATP activated BMP/Smad signaling pathway.
研究领域:
组织工程
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
Natural Products and Bioprospecting
·
2026
·Vol. 16
·期 1
·13
·
IF 4.9
Mei Mei,Sun Huawei,Zhang Kai,Zhang Feng,Sun Shiqing,Zhang Yu
In this study, a diabetic nephropathy (DN) rat model was established using 2% Streptozocin (STZ) solution, and an in vitro DN model was constructed by stimulating HK-2 cells with 30 mM glucose to investigate the mechanism of Phellodendron amurense Rupr. Polysaccharides (PAP) in ameliorating DN. Results demonstrated that PAP, a neutral homogeneous polysaccharide with molecular weight of 1.98 × 105 Da composed of Rha, GalA, Gal, and D-Xyl, exerted renal protective effects through multiple pathways. It enhanced renal antioxidant capacity and alleviated oxidative damage in DN by upregulating PI3K/AKT pathway-related protein expression. Simultaneously, PAP activated the TGF-β/Smad pathway via Nrf2 to mitigate renal fibrosis symptoms in DN, while inhibiting cellular apoptosis. Furthermore, PAP suppressed renal inflammation through gut microbiota reduction, thereby protecting against renal injury in DN rats. This study reveals that PAP alleviates DN symptoms by modulating gut microbiota, enhancing antioxidant and anti-fibrotic capacities, and inhibiting apoptotic pathways, comprehensively elucidating its multifaceted therapeutic mechanisms against DN. Graphical
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高影响因子
CARBOHYDRATE POLYMERS
·
2026
·
IF 13.2
Hao Yuan,Xin Xu,Jie Gao,Yu Cao,Can Jin,Kan Ding,Wenfeng Liao
Macrophages can secrete various cytokines associated with liver fibrosis. Galactomannoglucan may activate macrophages. We further hypothesize that galactomanoglucan might impact liver fibrosis. Here we report a novel homogeneous branched galactomannoglucan, AW1, from Acorus tatarinowii , composed of Man, Rha, Glc, Gal, Xyl, and Ara with a molar ratio of 10.8: 0.9: 23.1: 9.2: 6.8: 7.3. AW1 has a backbone composed of alternating 1, 4-linked Glc p and 1, 4-linked Man p residues with branches at the C-6 position of 1,4, 6-linked Glc p, and terminal Xyl p , and an arabinogalactan composed of Gal p , Ara f , and terminal T-Glc p . Interestingly, AW1 markedly inhibits transforming growth factor-β (TGF-β)-induced activation of human hepatic stellate cell (LX-2) in vitro and alleviates carbon tetrachloride (CCl₄)-induced liver fibrosis in mice upon oral administration . Mechanism studies reveal that AW1 suppresses the expression of the Trk-fused gene protein (TFG) and the secretion-defective gene (SEC), thereby attenuating the TFG/SEC trafficking pathway and ultimately blocking the transport of collagen from the endoplasmic reticulum (ER) into the Golgi apparatus (Golgi). Simultaneously, AW1 may dramatically impede the TGF-β/Smad signaling pathway. Accordingly, AW1 shows dual regulatory actions on mitigating hepatic fibrogenesis. The above evidence suggests that AW1 may be a promising lead compound for the development of new anti-liver fibrosis drugs.
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PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Zhengchuan Zhang,Jiaqi Shen,Ruogu Xu,Yang Yang,Xiaolin Yu,Dongsheng Yu,Feilong Deng
Critical bone defect with soft tissue fenestration poses a significant therapeutic challenge without the premise of barrier periosteum in situ for the relatively independent repair spaces of soft tissue and bone. Inspired by the regenerative functions of mesenchymal stem cells (MSCs)-derived small extracellular vesicles (sEVs) and the guided properties of in situ-generated periosteum, here we report the therapeutic benefits of dual-functional biomimetic periosteum (DBP) incorporating engineered sEVs for treating critical bone defect with soft tissue fenestration. We started our experiment with the construction of engineered sEVs via porous titanium-preconditioned MSCs-derived sEVs (Ti-sEVs). COL1A1 and MMP1 were enriched in Ti-sEVs with enhanced uptake efficiency of fibroblasts and bone marrow-derived MSCs for scarless soft tissue and bone repair abilities via TGF-beta1/SMAD pathway in vitro. DPB was constructed via the chemically crosslinking and lyophilized treatment of a xenogenic acellular dermal matrix. Incorporation and in vivo delivery of Ti-sEVs were successfully achieved via the controlled-release DPB with the characteristics of a loose surface facing the bone defect and a dense surface facing the soft tissue fenestration. DBP incorporating Ti-sEVs promoted the repair of the surrounding native periosteum in situ via the critical skull defect with skin fenestration models in rats. Bone repair with scarless soft tissue was achieved by enhanced angiogenesis and limited osteoclastic activity. Collectively, this dual-functional system could synergistically achieve critical bone defect regeneration with scarless soft tissue repair via TGF-beta1/SMAD pathway with the sustained release of Ti-sEVs, providing a promising strategy of engineered sEVs for preferable tissue regeneration.
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PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 4
·2385-2392
·
IF 1.448
Li Li,Qiuhong Li,Lei Wei,Zhongfu Wang,Wei Ma,Fangying Liu,Yanhua Shen,Shanfang Zhang,Xiulian Zhang,Huiping Li,Yechang Qian
Pulmonary fibrosis (PF) is a heterogeneous pathological process in lung tissues with a considerable mortality rate. Currently, combination therapy represents an effective approach to treat PF. Dexamethasone (Dxs) and berberine (BBR) are widely applied to inhibit the progression of PF. Dxs plus penehyclidine hydrochloride or alfacalcidol have been reported more effective in therapy compared with any single drug treatment. However, whether Dxs plus BBR induces an increased antifibrotic effect remains unknown. The current study aimed to evaluate the therapeutic effect of BBR plus Dxs in bleomycin (BLM)‑induced PF. A PF model in rats was established and rats were divided into control, BLM, BBR, Dxs and BBR plus Dxs groups (n=9/group). On days 3, 7 and 14, blood samples were collected from the eyes of the rats (n=6/group). CXC chemokine ligand 14 (CXCL14), collagen I, collagen III, matrix metalloproteinase (MMP)2 and MMP9 serum levels were measured by ELISA. On day 14, all rats were sacrificed. Hematoxylin and eosin analysis, Masson staining and hydroxyproline (Hyp) assessment were performed to observe histopathological changes and collagen deposition. mRNA and protein levels of CXCL14, CXC chemokine receptor 4 (CXCR4), collagen I/III, α‑smooth muscle actin (α‑SMA), MMP2/9 and phosphorylated‑Smad 2/3 in lung tissue were further evaluated. Similar effects in preventing lung damage were observed histopathologically for Dxs and BBR compared with the BLM group. These treatments further reduced levels of Hyp, CXCL14, CXCR4, collagen I/III, MMP2/9, α‑SMA and p‑Smad 2/3. The combination of Dxs and BBR exhibited increased effectiveness compared with the single treatments. Results further suggested that antifibrotic mechanisms were involved in inhibiting CXCL14 and MMP2/MMP9 expression, and preventing the activation of Smad2/3 and hedgehog signaling pathways. The combined use of Dxs and BBR may represent a potential therapeutic approach for PF.
研究领域:
药理学
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呼吸医学
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病理学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2023
·
IF 14
Hong-Lin Qian,Sheng-Yu Chen,Fan Jia,Wei-Pin Huang,Jing Wang,Ke-Feng Ren,Guo-Sheng Fu,Jian Ji
The valid management of inflammation and precise inhibition of smooth muscle cells (SMCs) is regarded as a promising strategy for regulating vascular responses after stent implantation , yet posing huge challenges to current coating constructions. Herein, we proposed a spongy cardiovascular stent for the protective delivery of 4-octyl itaconate (OI) based on a “spongy skin” approach, and revealed the dual-regulation effects of OI for improving vascular remolding. We first constructed a “spongy skin” onto poly-l-lactic acid (PLLA) substrates, and realized the protective loading of OI with the highest dosage of 47.9 μg/cm 2 . Then, we verified the remarkable inflammation mediation of OI, and surprisingly revealed that the OI incorporation specifically inhibited SMC proliferation and phenotype switching, which contributed to the competitive growth of endothelial cells (EC/SMC ratio ∼ 5.1). We further demonstrated that OI at a concentration of 25 μg/mL showed significant suppression of the TGF-β/Smad pathway of SMCs, leading to the promotion of contractile phenotype and reduction of extracellular matrix. In vivo evaluation indicated that the successful delivery of OI fulfilled the inflammation regulation and SMCs inhibition, therefore suppressing the in-stent restenosis. This “spongy skin” based OI eluting system may serve as a new strategy for improving vascular remolding, and provides a potential concept for the treatment of cardiovascular diseases.
研究领域:
心血管工程
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生物材料
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药物递送系统
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血管生物学
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组织工程
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2026
·Vol. 31
·期 12
·1990
·
IF 5.1
Jinghan Zhang,Yue Sun,Jinhao Zheng,Can Yang,Mingshuo Yang,Liming Pan
Dendrobium officinalehas attracted increasing attention as a functional food because of its diverse biological activities; however, the photoprotective potential of its protein-derived peptides remains poorly understood. In this study,D. officinaleprotein hydrolysates were fractionated by ultrafiltration according to molecular weight, and their protective effects against ultraviolet B (UVB)-induced photoaging were systematically evaluated in HaCaT keratinocytes. Among the tested fractions, low-molecular-weight peptide fractions exhibited relatively stronger antioxidant activity and effectively reduced intracellular reactive oxygen species (ROS) accumulation in UVB-irradiated cells. In addition, the peptide fractions alleviated UVB-induced inflammatory responses and decreased matrix metalloproteinase (MMP) expression, which was associated with modulation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Higher-molecular-weight fractions showed relatively stronger effects on maintaining skin barrier-related functions and were associated with regulation of transforming growth factor-β/Smad (TGF-β/Smad) signaling and collagen-related protein expression. Overall, these findings demonstrate functional differences amongDendrobium officinalepeptide fractions and suggest their potential application as natural photoprotective ingredients in functional foods and cosmeceutical products.
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PubMed
高影响因子
AQUACULTURE NUTRITION
·
2020
·Vol. 26
·期 5
·1792-1805
·
IF 2.231
Hua Rong,Fan Lin,Samwel Mchele Limbu,Zhideng Lin,Baoliang Bi,Tengfei Dou,Lei Zhao,Xiaobo Wen
Swim bladder is an ideal source of collagen production in fish for improved human health. Proline (Pro) is the main proteinogenic amino acid needed for collagen production. However, the effects of Pro supplementation on the swim bladder collagen synthesis have rarely been evaluated in fish. We determined the effects of dietary Pro supplementation on swim bladder collagen synthesis and its possible signalling pathway in spotted drum, Nibea diacanthus . A total of 450 N. diacanthus (100 ± 3.05 g) were randomly assigned into six treatments and fed with diets supplemented with different levels of Pro (0, 2.5, 5, 7.5, 10 and 12.5 g/kg of dry diet, hereafter P0, P1, P2, P3, P4 and P5, respectively) for 8 weeks. At the end, we evaluated collagen synthesis in swim bladder and the expression of genes related to TGF-β/Smad pathway in the fish. Dietary Pro levels increased significantly the contents of crude protein, total collagen (TC) and the levels of some amino acids in swim bladder than the control diet ( p < .05). The optimum amount of dietary Pro inclusion in diets for swim bladder collagen synthesis in N. diacanthus was 7.6 and 7.5 g/kg based on crude protein and TC in swim bladder, respectively. Dietary Pro levels increased significantly the proline 4-hydroxylase ( P4H ) content in fish serum, swim bladder, muscle and liver tissues than control ( p < .05). The relative expression of collagen type I alpha 1 ( COL1A1 ), alpha 2 ( COL1A2 ) and mothers against decapentaplegic homolog 2 ( Smad2 ) genes in liver and swim bladder initially increased significantly as the concentration of Pro and later decreased ( p < .05). Similarly, the relative expression of transforming growth factor beta ( TGF-β ), P4Ha2 and P4Ha3 genes in the swim bladder increased significantly as dietary Pro levels increased ( p < .05). Using K -means clustering analysis, dietary proline partly promoted collagen accumulation in swim bladder through upregulation of Smad2 and TGF-βRT genes. Taken together, Pro affected the collagen metabolism in swim bladder, probably by regulating the TGF-β/Smad pathway, most likely via transient overexpression of Smad2 gene.
研究领域:
水产养殖
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营养学
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分子生物学
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鱼类生理学
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Lijun Fang,Linmao Lyu,Hongyu Zhong,Jiamao Lin,Pengtao Ren,Yu Wang,Yunhong Yin,Mengyu Zhang,Yiqing Qu
Idiopathic pulmonary fibrosis (IPF) is a kind of chronic and progressive interstitial lung disease of unclear aetiology. A key aspect of IPF is transforming growth factor-β1 (TGF-β1)-induced mitophagy dysfunction and senescence in lung fibroblasts. Mesenchyme homeobox 1 (MEOX1) is a critical transcription factor in the regulation of cell differentiation. However, the role of MEOX1 in the pathogenesis of lung fibrosis and mitophagy has not been clarified. In this study, RNA-sequencing analysis was employed to identify the differentially expressed genes in TGF-β1-treated lung fibroblasts and IPF lung tissue. In vivo , the mouse model of lung fibrosis was established by intratracheal injection of bleomycin (BLM), and fibroblast-specific knockdown of MEOX in mice was achieved by intratracheal injection of adeno-associated viruse-shMEOX1. And in vitro experiments were also carried out on human lung fibroblasts. Our results indicated that fibroblast-specific knockdown of MEOX1 protected mice from BLM-induced pulmonary fibrosis, connective tissue growth factor (CTGF) expression, and lung fibroblast activation, as well as mitophagy deficiency and senescence. In vitro , MEOX1 knockdown abolished TGF-β1-induced mitophagy deficiency by downregulating CTGF expression, thereby inhibiting senescence, over-activation and collagen production in lung fibroblasts. Furthermore, we also found that TGF-β1 upregulated the expression of MEOX1 through the NOX4-ROS-Smad pathway. In conclusion, MEOX1 knockdown may ameliorate pulmonary fibrosis by regulating mitophagy and senescence and may be a potential therapeutic target for IPF and other types of interstitial lung diseases.
研究领域:
分子生物学
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细胞生物学
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呼吸病学
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遗传学
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生物信息学
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病理学
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产品关联
DOI
PubMed
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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PubMed
高影响因子
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