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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高影响因子
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
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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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
·
营养学
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分子生物学
·
鱼类生理学
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高影响因子
NEW JOURNAL OF CHEMISTRY
·
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
·
生物医学工程
·
化妆品科学
·
分子生物学
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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
BIOMATERIALS
·
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
·
药物递送系统
·
血管生物学
·
组织工程
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高影响因子
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
·
2023
·
IF 1.9
Wenchao Pan,Yadong Wang,Caiyan Zhao
Objective To explore the protective effect and related mechanism of miR-140-5p on liver fibrosis by interfering with TGF-β/Smad signaling pathway.Methods Liver fibrosis mice models were established by intraperitoneal injection of CCL4. Hematoxylin and eosin (HE) staining was used to detect the structural and morphological changes of the liver. Masson staining was used to detect collagen deposition. Human hepatic stellate cells (HSCs, LX-2) were transfected with miR-140-5p mimic or inhibitor then treated with TGF-β1. The qRT-PCR and Western blotting was used to detect the expression of related molecules. The luciferase reporter assay was used to identify the target of miR-140-5p.Results Our results indicated that miR-140-5p expression was downregulated in fibrotic liver tissues of model mice and LX-2 cells treated with TGF-β1. The overexpression of miR-140-5p decreased the expression of collagen1(COL1) and α-smooth muscle actin(α-SMA), inhibited the phosphorylation of Smad-2/3 (pSmad-2/3) in LX-2 cells. Conversely, the knockdown of miR-140-5p upregulated COL1 and α-SMA expression, increased Smad-2/3 phosphorylation. A dual-luciferase reporter assay showed that TGFβR1 was a target gene of miR-140-5p. The overexpression of miR-140-5p suppressed TGFβR1 expression in LX-2 cells. Additionally, knockdown of TGFβR1 decreased the expression of COL1 and α-SMA. Conversely, the overexpression of TGFβR1 reversed the inhibitory effect of miR-140-5p upregulation on expression of COL1 and α-SMA.Conclusion miR-140-5p bound to TGFβR1 mRNA 3′-untranslated region(3′UTR) and inhibited the expression of TGFβR1, pSmad-2/3, COL1 and α-SMA, thereby exerting a potential therapeutic effect on hepatic fibrosis.
研究领域:
分子生物学
·
肝病学
·
药理学
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·791
·
IF 12.6
Qiao Wenyu,Yang Luling,Liu Yu,Zhang Huaiyuan,Zheng Zhihuan,Gu Tianheng,Zhu Jiaxi,Hu Xinyi,Li Gangze,Zhang Yuxia,Xiao Meng,Zhang Lin
Excessive accumulation of reactive oxygen species (ROS) and dysbiosis of the gut microbiota are pivotal contributors to the pathogenesis of inflammatory bowel disease (IBD) and associated fibrosis. In this study, a microfluidic approach was utilized to fabricate a multifunctional therapeutic microsphere system by encapsulating hollow mesoporous cerium oxide nanoparticles (HCeO 2 ) loaded with KP1 short peptides-specific inhibitors of the TGF-β/Smad signaling pathway. The resulting composite formulation (KP1@HCeO₂@SAM) was designed to achieve synergistic antioxidant, anti-inflammatory, and antifibrotic effects. The developed microspheres exhibited prolonged intestinal retention and effectively modulated gut microbiota composition, increasing the relative abundance of probiotic species by over sevenfold. Moreover, they demonstrated remarkable reactive oxygen species (ROS) scavenging efficiency (> 95%) and significant inhibition of fibrotic signaling cascades. In dextran sulfate sodium (DSS)-induced murine colitis models, treatment with the microspheres led to a substantial reduction in Disease Activity Index (DAI) (> 76%), restoration of intestinal barrier integrity (> 90%), and mitigation of fibrotic progression, as indicated by a 66% decrease in α-SMA expression. These findings establish a novel and integrative therapeutic platform for the effective management of IBD. Graphical abstract
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高影响因子
Biomaterials Advances
·
2025
·
IF 6
Chen Shen,Xingyu Zhou,Junhui Jiang,Junbo Dang,Tong Lin,Ruibo Hu,Tianhao Zhao,Dahui Sun,Mei Zhang
Soft tissue fillers have received much attention for the treatment of skin aging and the restoration of missing or excised soft volumes. However, the development of fillers with both safety and applicability remains a challenge. This study presented a synergistic composite filler comprising aldehyde-modified hyaluronic acid (OHA), hydrazide-modified hyaluronic acid (NHA), amino-modified poly-L-lactic acid microspheres (NPLLA), and antioxidant copper peptide. The hydrogel formed in situ via Schiff base reaction exhibited excellent mechanical properties and immediate filling effect. The amino-modified PLLA microspheres were less likely to agglomerate, avoiding the occurrence of adverse reactions and further enhancing the mechanical properties of the filler. The timed-release platform provided protection for copper peptide stability, scavenged reactive oxygen species during the fibrotic encapsulation phase, and synergistically promoted collagen deposition. In a nude mice skin aging model, hydrogels stimulated collagen production through the TGF-β/Smad signaling pathway with good long-term filler efficacy. Therefore, NPLLA microspheres/hyaluronic acid-based composite hydrogels exhibit great potential as injectable soft tissue fillers.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
皮肤科学
·
药物递送
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高影响因子
Journal of Biomedical Nanotechnology
·
2018
·Vol. 14
·期 12
·2135-2145
·
IF 5.068
Chen Xiaoyu,Qin Zainen,Zhao Jinmin,Yan Xiaohui,Ye Jing,Ren En,Wang Junqing,Yang Xingchen,Heng Shujun,Zheng Li,Liu Gang
Mesenchymal stem cells (MSCs) have potential uses for cartilage repair due to the potential of chondrogenic differentiation. However, developing effective approaches to regulate chondrogenesis in vivo remains a big challenging. To address the limitations, we propose the application
of magnetic fields, which features excellent performance for tissue penetration, good biocompatibility even at high magnetic strength, and wireless remote control. To test this concept, a pulsed magnetic field (PMF) was used to enhance the chondrogenesis of SPIO-labeled MSCs in a rat model
of cartilage defects. The SPIO labeling not only efficiently strengthens the responsiveness of MSCs to the externally applied PMF but also enables in vivo non-invasive monitoring of MSCs with magnetic resonance imaging (MRI). Importantly, biochemical and gene expression analysis reveal
the upregulation of certain cartilage biomarkers (i.e., SOX9 and COL2A1), showing that the PMF improves the chondrogenesis of MSCs via activation of the TGF-β/SMAD signaling pathways. These results indicate a promising scheme for stem cell-based cartilage repair.
研究领域:
生物医学工程
·
干细胞生物学
·
再生医学
·
骨科
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高影响因子
HISTOCHEMISTRY AND CELL BIOLOGY
·
2023
·
IF 2.3
Jin Xin,Xu Hainan,Hu Qing,Yin Yitong,Qin Meiying,Xia Zhijun
Pelvic organ prolapse (POP) is a common disorder among women that negatively affects women’s quality of life. Early growth response 2 (EGR2) is a transcription factor that regulates cell growth. The present study aimed to explore the role of EGR2 in POP progression and provided a new target for the treatment and prevention of POP. Firstly, we extracted primary vaginal anterior wall fibroblasts from POP tissues and non-POP tissues and then constructed an EGR2-silencing lentivirus for further study. Immunoblotting, qPCR, TUNEL assay, CCK-8 assay, dual luciferase assay, and ELISA assay were carried out. EGR2 expression was much higher in POP tissues than in control tissues, and EGR2 expression positively correlated with cytokine signaling 3 (SOCS3) expression. Knockdown of EGR2 increased cell proliferation, upregulated PCNA expression, and reduced apoptosis in POP fibroblasts. Moreover, we found that the knockdown of EGR2 increased COL1A1 , COL3A1 , and Elastin expression and decreased MMP2 and MMP9 activities, and knockdown of EGR2 increased TGF-β/Smad pathway activity in POP fibroblasts. Interestingly, the results of dual luciferase assay demonstrated that EGR2 was able to increase SOCS3 transcriptional activity. EGR2 knockdown alleviated the apoptosis of POP fibroblasts by reducing SOCS3 expression and improving the proliferation and collagen synthesis of POP fibroblasts. Overall, our study illustrated that EGR2 was highly expressed in POP tissues, and knockdown of EGR2 alleviated apoptosis and reduced matrix degradation in POP fibroblasts. This study might provide a new insight into the pathogenesis of POP.
研究领域:
妇科学
·
分子生物学
·
细胞生物学
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高影响因子
危险品化学品经营许可证（带存储）