International Journal of Nanomedicine
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2017
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IF 4.3
Fei Tong,Bo Dong,Rongkui Chai,Ke Tong,Yini Wang,Shipiao Chen,Xinmei Zhou,Daojun Liu
The purpose of the research was to explore the therapeutic action of simvastatin-loaded poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) (PEG-b-PBLG50) on intestinal ischemia/reperfusion injury (II/RI) through downregulating bone morphogenetic protein 4 (BMP4)/cyclooxygenase-2 (COX-2) pathway as compared to free simvastatin (Sim). Sprague Dawley rats were preconditioned with 20 mg/kg Sim or simvastatin/PEG-b-PBLG50 (Sim/P) compounds, and then subjected to 45 min of ischemia and 1 h of reperfusion. The blood and small intestines were collected, serum levels of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α, and nitric oxide (NO) were checked, and the dry/wet intestine ratios, superoxide dismutase activity, myeloperoxidase content, reactive oxygen species, endothelial nitric oxide synthase, protein 47 kDa phagocyte oxidase (p47phox), BMP4, COX-2, and p38 mitogen-activated protein kinase (p38MAPK) expressions were measured in intestinal tissues. Both Sim and Sim/P pretreatment reduced intestinal oxidative damnification, restricted inflammatory harm, and downregulated the BMP4 and COX-2 expressions as compared to II/RI groups, while Sim/P remarkably improved this effect.
研究领域:
药理学
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病理学
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DOI
PubMed
高影响因子
MOLECULAR BIOTECHNOLOGY
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2023
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IF 2.6
Liu Hu,Li Tao,Ma Ben,Wang Yue,Sun Jun
Osteoblast regeneration, characterized by osteoblast differentiation, is the basis of fracture healing and accelerates fracture repair. It has been reported that hyaluronan and proteoglycan link protein 1 (HAPLN1) is overexpressed during osteoblast differentiation and regulates cartilage regeneration, but its function in fracture healing remains unclear. To elucidate this issue, we collected clinical blood samples of fracture healing, established a femoral fracture rat model, and induced an osteoblast differentiation cell model. We found that HAPLN1 was overexpressed in the serum of patients with fracture healing and the bone tissues of rats with fracture healing. Furthermore, the expression of HAPLN1 was increased time dependently during the osteogenic differentiation of MC3T3-E1 cells. HAPLN1 silencing prevented osteoblast differentiation and mineralization in MC3T3-E1 cells as evidenced by decreased osteoblast differentiation-related factors, suppressed alkaline phosphatase activities, and reduced alizarin red positive staining. Mechanically, the bone morphogenic protein 4 (BMP4)/Smad1/5/8 pathway, a facilitator of osteoblastic differentiation, was found to be inhibited by HAPLN1 knockdown, and inhibition of BMP4/Smad1/5/8 signaling enhanced the effects caused by HAPLN1 silencing. These findings demonstrated that HAPLN1 might promote fracture healing by facilitating osteogenic differentiation through the BMP4/Smad1/5/8 pathway, indicating that targeting HAPLN1 may be a feasible therapeutic candidate for fracture repair. Graphical Abstract
研究领域:
骨科
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细胞生物学
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分子生物学
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PubMed
高影响因子
Cell Journal
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2021
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IF 2.479
Sadaf Mahboudi,Kazem Parivar,Zohreh Mazaheri,Shiva Irani
Objective Numerous evidence indicates that microRNAs (miRNAs) are critical regulators in the spermatogenesisprocess. The aim of this study was to investigate Mir-106b cluster regulates primordial germ cells (PGCs) differentiationfrom human mesenchymal stem cells (MSCs). Materials and Methods In this experimental study, samples containing male adipose (n: 9 samples- age: 25-40 years)were obtained from cosmetic surgeries performed for the liposuction in Imam Khomeini Hospital. The differentiationof MSCs into PGCs was accomplished by transfection of a lentivector expressing miR-106b . The transfection of miR-106b was also confirmed by the detection of a clear green fluorescent protein (GFP) signal in MSCs. MSCs weretreated with bone morphogenic factor 4 (BMP4) protein, as a putative inducer of PGCs differentiation, to induce thedifferentiation of MSCs into PGCs (positive control). After 4 days of transfection, the expression of miR-106b , STELLA,and FRAGILIS genes was evaluated by real-time polymerase chain reaction (PCR). Also, the levels of thymocytedifferentiation antigen 1 (Thy1) protein was assessed by the western blot analysis. The cell surface expression of CD90was also determined by immunocytochemistry method. The cytotoxicity of miR-106b was examined in MSCs after 24,48, and 72 hours using the MTT assay. Results MSCs treated with BMP4 or transfected by miR-106b were successfully differentiated into PGCs. The resultsof this study also showed that the expression of miR-106b was significantly increased after 48 hours from transfection.Also, we showed STELLA, FARGILIS , as well as the protein expression of Thy1, was significantly higher in MSCstransfected by lentivector expressing miR-106b in comparison with MSCs treated with BMP4 (P≤0.05). MTT assayshowed miR-106b was no toxic during 72 hours in 1 µg/ml dose, that this amount could elevated germ cells markersignificantly higher than other experimental groups (P≤0.05). Conclusion According to this findings, it appears that miR-106b plays an essential role in the differentiation of MSCsinto PGCs.
研究领域:
分子生物学
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生殖医学
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干细胞研究
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DOI
PubMed
高影响因子
iScience
·
2026
·Vol. 29
·期 8
·116972
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IF 4.5
Yueyue Jin,Yue Zhang,Yingying Liu,Maolin Yao,Chenjie Zhang,Shuzi Li,Yibo Ding,Zhuan Niu,Yue Han,Yan Geng,Lian Li,Xue Liu,Wen Ning
Summary Trachea is a wide tube with smooth luminal epithelia that enables efficient ventilation. In this study, we provide the evidence that the mitotic angles of most tracheal epithelial cells exhibit ordered and transverse orientations, which allows the tracheal lumen to grow along the anterior-posterior (AP) axis, with its circumference being higher than length. We show that the BMP4 signaling antagonist follistatin-like 1 (Fstl1) is a critical regulator for tracheal morphogenesis. Mice with Fstl1 deletion exhibit wider trachea with enlarged lumen as a result of the increased proportion of mitotic cells with their spindles nearly vertical to the tracheal longitudinal axis. Mechanistically, Fstl1 regulates BMP4 signaling by antagonizing p -Smad1/5/8 in tracheal epithelial cells. Reducing BMP4 signaling activity rescues lumen enlargement and normalizes the spindle angle distribution in Fstl1 -deficient tracheas. Therefore, we provide evidence to demonstrate that Fstl1 modulates the oriented cell division and tracheal morphogenesis, in part, through BMP4 signaling.
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PubMed
高影响因子
Frontiers in Nutrition
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2024
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IF 4
Liu Xiaojie,Jiang Xi,Hu Jing,Ding Mingxing,Lee Sang Ki,Korivi Mallikarjuna,Qian Yongdong,Li Ting,Wang Lifeng,Li Wei
Background: Perivascular adipose tissue (PVAT) dysfunction impairs vascular homeostasis. Impaired inflammation and bone morphogenetic protein-4 (BMP4) signaling are involved in thoracic PVAT dysfunction by regulating adipokine secretion and adipocyte phenotype transformation. We investigated whether aerobic exercise training could ameliorate high-fat diet (HFD)-induced PVAT dysfunction via improved inflammatory response and BMP4-mediated signaling pathways.Methods: Sprague-Dawley rats (n = 24) were divided into three groups, namely control, high-fat diet (HFD), and HFD plus exercise (HEx). After a 6-week intervention, PVAT functional efficiency and changes in inflammatory biomarkers (circulating concentrations in blood and mRNA expressions in thoracic PVAT) were assessed.Results: Chronic HFD feeding caused obesity and dyslipidemia in rats. HFD decreased the relaxation response of PVAT-containing vascular rings and impaired PVAT-regulated vasodilatation. However, exercise training effectively reversed these diet-induced pathological changes to PVAT. This was accompanied by significantly (p < 0.05) restoring the morphological structure and the decreased lipid droplet size in PVAT. Furthermore, HFD-induced impaired inflammatory response (both in circulation and PVAT) was notably ameliorated by exercise training (p < 0.05). Specifically, exercise training substantially reversed HFD-induced WAT-like characteristics to BAT-like characteristics as evidenced by increased UCP1 and decreased FABP4 protein levels in PVAT against HFD. Exercise training promoted transcriptional activation of BMP4 and associated signaling molecules (p38/MAPK, ATF2, PGC1α, and Smad5) that are involved in browning of adipose tissue. In conjunction with gene expressions, exercise training increased BMP4 protein content and activated downstream cascades, represented by upregulated p38/MAPK and PGC1α proteins in PVAT.Conclusion: Regular exercise training can reverse HFD-induced obesity, dyslipidemia, and thoracic PVAT dysfunction in rats. The browning of adipose tissue through exercise appears to be modulated through improved inflammatory response and/or BMP4-mediated signaling cascades in obese rats.
研究领域:
心血管生理学
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代谢紊乱
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运动生理学
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2024
·Vol. 14
·期 1
·1-13
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IF 3.8
Zhu Dongsheng,Chen Feng,Qiang Hongjia,Qi Han
To clarify the impact of SETD2 on macrophage function in pediatric patients with acute suppurative osteomyelitis and to elucidate the precise underlying mechanism. To gain insights into the potential functions of SETD2, a comprehensive study was conducted utilizing a co-culture model of human bone mesenchymal stem cells (hBMSCs) and bone marrow-derived macrophages (THP-1). A range of techniques were employed, including quantitative polymerase chain reaction, western blotting, ELISA, alkaline phosphatase activity assays, alizarin red S staining, luciferase reporter gene assays, and chromatin immunoprecipitation, to unravel the intricate interactions and molecular mechanisms involving SETD2 in this system. It was observed that SETD2 expression was reduced in THP-1 cells stimulated by staphylococcal protein A (SPA). Furthermore, the downregulation of SETD2 resulted in elevated M1 macrophage polarization and glycolysis, effects that were mitigated by SPA stimulation. Notably, SPA-stimulated THP-1 cells exhibited an increase in HIF-1α expression, which exhibited an inverse correlation with SETD2 levels. Moreover, it was discovered that SETD2 functioned as a catalyst for H3K36me3 and bound to the HIF-1α gene, which, in turn, regulated HIF-1α expression. Furthermore, the suppression of HIF-1α abrogated the consequences of SETD2 downregulation on glycolysis and M1 macrophage polarization. Lastly, the study demonstrated that M1 macrophage polarization serves as a mediator for BMP4’s inhibitory effect on osteogenic differentiation of hBMSCs. This research has uncovered a previously unknown role of SETD2 in macrophages during osteomyelitis, revealing its significance in the pathogenesis of this condition. These findings suggest SETD2 as a novel target for the treatment of osteomyelitis.
研究领域:
免疫学
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分子生物学
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细胞生物学
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骨科
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DOI
PubMed
高影响因子
npj Science of Food
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2026
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IF 9.7
Zhou Yunxiao,Lu Yiguang,Xiang Qing,Song Xiaochao,Yang Wei,Zhao Yangfei,Liang Chen,Bai Jian,Cheng Mengyu,Zhang Jianhai
As a widely distributed hazardous substance in agriculture and food, arsenic has become a global public health concern. Riboflavin is known for its anti-inflammatory and antioxidant properties, but whether it mitigates arsenic-induced male reproductive damage remains unclear. To clarify arsenic’s reproductive toxicity, network toxicology was first used to identify potential targets. Subsequently, thirty-six 4-week-old male mice were administered arsenic trioxide (5 mg/L in drinking water) and/or riboflavin (10 mg/kg in diet) for 22 weeks to establish a riboflavin intervention model. Network toxicology identified that arsenic induces male infertility via multiple signaling pathways, such as the TGF-β signaling pathway. In vivo, arsenic diminished sperm quality, caused histopathological damage, and impaired both blood-testis barrier integrity and Sertoli cell proliferation, while riboflavin effectively mitigated these detrimental effects. In vitro, TM4 cell experiments further confirmed that riboflavin reversed arsenic-induced decline in cell viability and cytoskeletal damage. This study is the first to demonstrate that the protective effect of riboflavin is mainly attributed to its ability to mediate the binding of Bmp4 to Bmpr1α, thereby reversing arsenic-induced toxicity, providing a new perspective for exploring riboflavin’s role in alleviating arsenic toxicity.
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DOI
高影响因子
ACS Biomaterials Science & Engineering
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2024
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IF 5.4
Yixiao Chen,Guoqing Li,Yufeng Ge,Su Liu,Jian Weng,Jianjing Lin,Ao Xiong,Hui Zeng,Xinbao Wu,Jun Yang,Fei Yu
In this study, we explore the cartilage defect repair mechanism by phosphocreatine-grafted chitosan hydrogels loaded with berberine-treated ATDC5 cells (CSMP@BBR@ATDC5). Under the optimal concentrations of LPS and BBR ideal conditions, ATDC5 cell toxicity and proliferation were detected with AM/PI and EdU staining. Additionally, qPCR and Western blot were employed to detect the expression of the SIRT1/BMP4 signaling pathway and chondrogenic-related factors in ATDC5 cells. Moreover, BBR-treated ATDC5 was seeded into a phosphocreatine-grafted chitosan hydrogel system. Subsequently, the cartilage defect was established in mice. After 4, 8, and 12 weeks, knee specimens were collected to evaluate the repair of cartilage defects. According to our findings, BBR can increase ATDC5 viability by LPS treatment. Likewise, it upregulates the SIRT1/BMP4 signaling pathway expression and chondrogenic-related factors. Another, it was shown by histological observation that the cartilage defect had been repaired more effectively in the CSMP@BBR@ATDC5 group than in the other groups. Finally, the expressions of chondrogenic-related factors and SIRT1/BMP4 signaling pathway were upregulates in CSMP@BBR@ATDC5 than in other groups. In vitro, BBR protects inflammatory ATDC5 cells and maintains the expression of chondrogenic-related factors. Subsequently, we successfully use CSMP@BBR@ATDC 5 to repair knee cartilage defects in mice.
研究领域:
组织工程
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再生医学
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骨科
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2018
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IF 6.434
Mengmeng Huang,Jingjing Jiao,Jun Wang,Zhidan Xia,Yu Zhang
Acrylamide (AA) is a high production volume chemical in industrial applications and widely found in baked or fried carbohydrate-rich foods. In this study, we unravelled that AA induced developmental toxicity associated with oxidative stress status and disordered lipid distribution in heart region of developing zebrafish. Treatment with AA caused a deficient cardiovascular system with significant heart malformation and dysfunction. We also found that AA could reduce the number of cardiomyocytes through the reduced capacity of cardiomyocyte proliferation rather than cell apoptosis. The cardiac looping and ballooning appeared abnormal though cardiac chamber-specific identity in the differentiated myocardium was maintained well after AA treatment through MF20/S46 immunofluorescence assay. Furthermore, treatment with AA disturbed the differentiation of atrioventricular canal, which was demonstrated by the disordered expressions of the atrioventricular boundary markers bmp4 , tbx2b and notch1b and further confirmed by the ectopic expressions of the cardiac valve precursor markers has2 , klf2a and nfatc1 through whole-mount in situ hybridization. Thus, our studies provide the evidence of cardiac developmental toxicity of AA in the cardiovascular system, and also raised health concern about the harm of trans-placental exposure to high level of AA for foetuses and the risk of high exposure to AA for the pregnant women.
研究领域:
毒理学
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发育生物学
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心血管科学
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分子生物学
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DOI
PubMed
高影响因子
Food & Function
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2017
·Vol. 8
·期 9
·3259-3270
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IF 3.247
Xiaozhou Zhou,Shiguo Chen,Xingqian Ye
The anti-obesity effects of different proanthocyanidin extracts (PE) from Chinese bayberry (Myrica rubra Sieb.et Zucc.) leaves were evaluated in a high-fat (HF) diet-induced obese rat model. The leaves of Chinese bayberry (LCB), a non-desaccharified proanthocyanidin extract (NDPE), and a desaccharified proanthocyanidin extract (DPE) were compared with orlistat, a conventional anti-obesity drug used as a positive control. The rats from all of the PE-treated groups showed obvious weight loss, with the greatest weight loss in the DPE group (P < 0.05). Compared to the HF group, almost all of the PE-treated groups showed significantly reduced levels of serum TC, TG, AST, ALT, ALP, LDL-C, ADP and a LEP/ADP ratio, and increased levels of HDL-C and LEP. Furthermore, the expression levels of SIRT1, PPAR-γ, C/EBP-α, BMP4 and UCP1 were investigated in the liver, kidney, epididymis and abdominal adipose tissue. Compared to the HF group, PPAR-γ and C/EBP-α levels were significantly reduced and SIRT1, BMP4 and UCP1 levels were significantly upregulated in the DPE-treated group. Our results suggested that PE exerted its anti-obesity effects by upregulating the expression of SIRT1, thus inducing the deacetylation of PPAR-γ and downregulating the expression of C/EBP-α, and also upregulating the expression of BMP4 to boost the levels of brown fat.
研究领域:
药理学
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营养学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
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IF 18.5
Yiyue Hong,Mengyang Wang,Daorun Hu,Yujia Wang,Shuaifei Ji,Jiangbing Xiang,Hongliang Zhang,Huating Chen,Yan Li,Mingchen Xiong,Wei Pi,Qianyi Wang,Xinling Yang,Yingying Li,Chaochen Shui,Xiaolei Wang,Xiaobing Fu,Xiaoyan Sun
Efficient wound repair with skin appendage regeneration following severe trauma poses a challenge due to the scarcity of skin grafts and decreased drug effectiveness in protease-rich wound microenvironments. Here, a multifunctional artificial skin (NIR-mFAS) with photothermal-triggered drug delivery capabilities is designed to actively and comprehensively improve the regenerative potential of full-thickness wounds. The antibacterial chitosan/silk fibroin hydrogel matrix of artificial skin, cross-linked by electrostatic interactions, effectively encapsulates and sustains the release of epidermal growth factor (EGF) to accelerate re-epithelialization and neovascularization by promoting the migration and proliferation of repair cells. Subsequently, the photothermal responsive polydopamine nanoparticles (PDA-NPs) dispersed in the matrix enable precise control over the release of BMP4 under the irradiation of 1064 nm NIR, thereby inhibiting scarring by reducing myofibroblasts during the proliferative stage. Importantly, the concurrent controlled release of CHIR99021 can modulate cell fate by inducing the conversion of myofibroblasts into dermal papilla-like cells, leading to hair follicle and sebaceous gland regeneration. The NIR-mFAS functions as an advanced delivery system for achieving high-quality wound healing with appendage regeneration and offers a smart therapeutic approach that can be applied to other treatments requiring coordinated delivery of multiple pharmacological agents.
研究领域:
生物医学工程
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再生医学
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药学
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材料科学
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组织工程
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）