JOURNAL OF APPLIED TOXICOLOGY
·
2024
·
IF 2.7
Hongmei Chang,Siqi Zhao,Yuzhu Lei,Yunhua Hu,Yizhong Yan,Guanling Song
Titanium dioxide nanoparticles (nano-TiO 2 ) can cause a reduction in sperm counts, and lactate production in Sertoli cells plays a key role in spermatogenesis. The aim of this study was to evaluate the effect of nano-TiO 2 on lactate production in mouse Sertoli cell line (TM4 cells) and to investigate whether the effect is mediated through the PI3K/AKT/HIF-1α pathway. After TM4 cells were treated with different concentrations of nano-TiO 2 for 48 h, cell viability, contents of glucose and lactate, and the expression levels of GLUT3 and key enzymes (HK1, HK2, PFKM, ENO1, LDH) during lactate production were detected. PI3K/AKT/HIF-1α pathway proteins were measured. In addition, PI3K agonist (IGF-1) was added to explore whether nano-TiO 2 regulates HIF-1α through PI3K/AKT pathway, thereby affecting the production of lactate in TM4 cells. The results showed that nano-TiO 2 significantly inhibited TM4 cell viability, increased glucose content, decreased lactate content, and downregulated the expression levels of GLUT3 and key enzymes during lactate production. Meanwhile, nano-TiO 2 decreased the expression of PI3K/AKT pathway phosphorylated proteins and HIF-1α, and IGF attenuated this effect of nano-TiO 2 . Collectively, nano-TiO 2 downregulated the expression level of proteins and enzymes related to lactate production in TM4 cells by inhibiting PI3K/AKT/HIF-1α pathway, resulting in the decrease of lactate production in TM4 cells.
研究领域:
生殖生物学
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细胞生物学
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纳米技术
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分子生物学
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 2
·80
·
IF 4.5
Lu Xuefei,Xu Kai,Zhou Zhenyu,Ding Gaonan,Zhang Yuan,Liang Yongwen,Zhou Jiahui,Jia Minglu,Zhang Yitang,Shen Li,Li Hualing
Alzheimer’s disease (AD) is a progressive neurodegenerative disease for which no effective clinical therapies currently exist. The neuroprotective potential of Chaetoglobosin F (CF), a fungal secondary metabolite, was investigated in this study using a Caenorhabditis elegans ( C. elegans ) model of AD that are transgenic nematodes expressing amyloid-beta (Aβ). Key parameters evaluated included paralysis rate, lifespan, motor and cognitive functions, Aβ plaque aggregation, intracellular reactive oxygen species (ROS), and autophagosome formation. The transcriptional levels of genes were examined by real time PCR. Results showed that treatment with CF significantly delayed paralysis, extended lifespan, and ameliorated Aβ-induced deficits in locomotion and chemotaxis. CF markedly reduced Aβ plaque accumulation, suppressed intracellular ROS levels, and promoted autophagosome formation. Furthermore, CF had potent inhibitory effects on acetylcholinesterase (AChE) activity. These beneficial effects were correlated with the upregulation of crucial genes, including daf-16 , skn-1 , pmk-1 , mtl-1 , unc-51 , bec-1 , lgg-1 , sod-1 and sod-3 , which confirmed the improving antioxidant defenses and autophagy. Our findings demonstrate that CF confers strong neuroprotection against Aβ-induced toxicity in C. elegans by co-regulating oxidative stress and autophagy through the Insulin/IGF-1 (IIS) and p38 MAPK signaling pathways. These results suggest that CF is a promising natural compound for further investigation as a potential therapeutic agent for AD. Graphical
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PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Lan Zeng,Kang Ma,Ying Huang,Bingqing Liao,Luyao Zhong,Yue Zhao,Yongling Lu,Kai Xu,Shi Wang,Ning Mu,Yaning Shi,Chuanyan Yang,Xianyong Fu,Rong Hu,Hua Feng,Qiang Zhang,Xiaoming Wang,Tunan Chen
Long-segment peripheral nerve injury (PNI) represents a significant global health challenge, often leading to sensory and motor deficits, neuropathic pain, and secondary complications. Early reconnection of injured nerves is essential for preserving function and minimizing sequelae. In this study, we present a novel Silk Fibroin-MXene (SF-MXene) pIGF1 GelMA Hydrogel Nerve Conduit as an effective solution to optimize the bio-electrical and cellular microenvironment, thereby accelerating nerve regeneration. Unlike standalone plasmid Insulin-like Growth Factor-1 (pIGF1) releasing conduits, which disrupt growth direction and attract non-neuronal repair cells that obstruct nerve elongation, this advanced conduit enhances directional nerve growth and myelination while facilitating efficient electrical signal transmission in PNI rats. In this multifunctional NGC, pIGF1 optimizes the cellular microenvironment by promoting Schwann cell proliferation and migration, while the conductive SF-MXene NGC supports spatially ordered distribution and accelerates nerve elongation. Additionally, the conduit sustains long-term RANKL upregulation, activating NF-κB signaling to drive Schwann cell differentiation into myelinating subtypes, thereby promoting efficient and durable myelination of regenerated nerves and facilitating effective electrical signal transmission. These findings underscore the potential of the Silk-MXene+pIGF1 Nerve Conduit as a promising strategy for long-segment nerve injury repair, with strong implications for future clinical applications.
研究领域:
生物医学工程
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神经组织工程
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再生医学
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生物材料
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神经科学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2025
·
IF 3
Chengxiang Yan,Haijiang Dong,Zhibin Li,Xinhao Cheng,Ximei Wang
Keloid are characterized by fibroblastic proliferation and excessive collagen deposition. Nicotinamide N-methyltransferase (NNMT) belongs to the methyltransferase family and plays an important role in various physiological processes, including keloid formation. However, the role of NNMT in keloid development remains poorly understood. In this study, we investigated the role of NNMT in keloids using a bleomycin (BLM)-induced fibrosis model in vivo and primary human keloid fibroblast (HPKF) in vitro. NNMT expression was upregulated in keloid tissues, and M2 macrophages were significantly increased in keloid tissue. NNMT overexpression reduced the SAM content, while NNMT knockdown increased it. Moreover, overexpression of NNMT enhanced the cell viability of HPKFs, while knockdown of NNMT promoted apoptosis. Additionally, NNMT overexpression promoted HPKF invasion and migration, whereas knockdown effectively inhibited these processes. Overexpression of NNMT also increased the expression of fibrosis-related markers, including FN1, COL1A1, COL3A1, Vimentin, and α-SMA, while NNMT knockdown reversed it. THP-1 cells were induced into THP1-M0 macrophages using PMA and co-cultured with HPKFs. Co-culturing with NNMT-overexpressing HPKFs promoted M2 polarization in M0 cells, while NNMT knockdown inhibited M2 polarization and reduced TGFB1 and Arg-1 expression in M0 cells. Furthermore, NNMT overexpression promoted IGF-1 expression, and treatment with AG1024 (an IGF1R inhibitor) suppressed NNMT-induced M2 polarization and inhibited IGF1B and Arg-1 expression. Taken together, our findings suggest that NNMT enhances the invasive and migratory capacity of keloid fibroblasts and regulates M2 macrophage polarization in keloids through IGF-1 modulation. These results highlight NNMT as a potential therapeutic target for keloid treatment.
研究领域:
皮肤病学
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细胞生物学
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免疫学
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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
Experimental and Therapeutic Medicine
·
2023
·Vol. 26
·期 2
·1-12
·
IF 2.7
Xiongfei Shi,Xingzhi Yu,Liping Yang,Xiaohua Duan
Gastrodia elata Blume is a traditional Chinese medicine with a long history, which has numerous pharmacological activities, such as anti‑inflammation, anti‑oxidation and protection of nerves. The present study investigated the regulatory effect of ethyl acetate extract of Gastrodia elata (EEGE) on the β‑amyloid (Aβ) toxicity of Caenorhabditis elegans (C. elegans). First, the main components of EEGE were analyzed using high‑performance liquid chromatography, and the total phenols, total flavonoids and total antioxidant capacity of EEGE were determined. Next, the regulation effect of EEGE on Aβ‑induced toxicity of C. elegans was evaluated through experiments on nematode paralysis, lifespan, oxidative and heat stress, locomotor ability, reproductive ability, reactive oxygen species (ROS) level, Aβ aggregation test, malondialdehyde (MDA) level, catalase (CAT) activity and superoxide dismutase (SOD) activity. Finally, the mechanism of EEGE was elucidated using RNA sequencing (RNA‑Seq) and the expression levels of related genes were verified using quantitative PCR. The present study revealed that the main components of EEGE included phosphorylated (p)‑hydroxybenzyl alcohol, p‑hydroxybenzaldehyde and 4,4'‑dihydroxydiphenylmethane, possessing strong in vitro free radical scavenging and reducing abilities. In addition, after the intervention of EEGE, the paralysis of nematodes could be delayed, the survival time of the nematodes was prolonged, the survival rate of the nematodes under stress (high temperature and oxidation) conditions was improved, the activity capacity and reproductive capacity of the nematodes were improved, the activities of SOD and CAT were improved and the levels of ROS and MDA were reduced. Notably, EEGE directly inhibited Aβ plaque aggregation in nematodes. RNA‑Seq analysis showed that EEGE regulated metabolism and longevity‑related genes, and these genes were regulated by the insulin/IGF‑1 signaling (IIS) pathway. Therefore, the present study hypothesized that the regulatory mechanism of EEGE was significantly related to the IIS pathway. The present research results demonstrated that the protective effect of EEGE on transgenic C. elegans was to reduce Aβ protein aggregation, improve the in vivo antioxidant level, effectively remove free radicals and to regulate the expression of genes related to IIS pathway, thereby reducing Aβ‑induced toxicity and delaying nematode paralysis.
研究领域:
药理学
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神经科学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
LIFE SCIENCES
·
2023
·
IF 6.1
Pan He,Guanhua Du,Xuemei Qin,Zhenyu Li
Aims Sarcopenia is an age-related syndrome characterized by a gradual loss of the muscle mass, strength, and function. It is associated with a high risk of adverse consequences such as poorer quality of life, falls, disability and mortality among the elderly. The aim in this study is to investigate the pathological mechanism of sarcopenia. Main methods The aging of skeletal muscle was investigated by the D-galactose induced accelerated aging model combining with constrained motion. After 10 weeks, muscle function and gastrocnemius muscle index, and morphology of muscle fibers were evaluated, and myostatin, IGF-1 and ATP in skeletal muscle were also determined. Then the mechanism of aging-related skeletal muscle dysfunctions was investigated based on untargeted serum metabolomics and 16S rRNA gene sequencing. Four key metabolites were validated by the D-galactose-induced C2C12 senescent cell model in vitro . Key findings Results showed that gastrocnemius muscle mass was decreased significantly, morphology of muscle fibers was altered, and muscle function was damaged in the aged group. Furthermore, increased MSTN, and decreased IGF-1 and ATP were also observed in the aging skeletal muscle. Importantly, alteration of the key pathways including riboflavin biosynthesis and energy metabolism contributed to the aging of skeletal muscle. Four key metabolites, including riboflavin, α-ketoglutaric acid and two dicarboxylic acids, which were involved in these metabolic pathways, could promote the proliferation of C2C12 cells. Significance These findings provide novel insights into pathological mechanism of sarcopenia, and will facilitate the development of therapeutic and preventive strategies for sarcopenia.
研究领域:
老年学
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肌肉生理学
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代谢组学
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微生物组研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Suwen Liu,Fanna Meng,Dong Zhang,Donglin Shi,Junyi Zhou,Shuo Guo,Xuedong Chang
Exercise fatigue can exert deleterious effects on the body. This study evaluated the effects and mechanisms by which Lonicera caerulea berry polyphenols extract (LCBP) improved the treadmill endurance of mice. Comparison was performed between the effects at 25°C and low temperatures (-5°C). Energy storage, product metabolism, and other biochemical indices were determined using vitamin C (VC) as a positive control. Co-immunoprecipitation was performed to detect the interaction between different proteins. Dietary supplementation with LCBP significantly prolonged the exhaustion time during treadmill exercise by 20.4% (25 °C) and 27.4% (-5 °C). LCBP significantly regulated the expression of antioxidant and inflammatory proteins, Bcl-2 /Bax apoptosis proteins, and the PKCα -NOx2 / Nox4 pathway proteins, and activated the expression of AMPK-PGC1α -NRF1-TFAM proteins in skeletal muscle mitochondria. The gene and protein expression of miRNA-133a/IGF-1/PI3K/Akt/mTOR in skeletal muscle cells was also activated. Molecular docking confirmed that the main components of LCBP such as cyanidin-3-glucoside, catechin, and chlorogenic acid, have strong binding affinity toward AMPKα. LCBP alleviates exercise fatigue in mice by reducing oxidative stress, inflammation, and apoptosis of skeletal muscle cells, enhances mitochondrial biosynthesis and cell proliferation, reduces fatigue, and enhances performance. These effects are also significant in a low-temperature environment (Graphical Abstract). Consequently, these results provide novel insights into the anti- fatigue roles of LCBP in exercise fatigue.
研究领域:
药理学
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生理学
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生物化学
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分子生物学
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运动科学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Fatemeh Maleki,Mohammad-Reza Rashidi,Habib Razmi,Marjan Ghorbani
A novel electrochemical immunosensor was developed for ultrasensitive determination of the hormone insulin-like growth factor 1 (IGF-1) based on immobilization of a specific monoclonal antibody on the electrospun nanofibers of Polyacrylonitrile (PAN)/Zein-reduced graphene oxide (rGO) nanoparticle . The nanofibers deposited on glassy carbon electrode (GCE) showed good electrochemical behaviors with synergistic effects between PAN, Zein, and rGO. PAN/Zein nanofibers were used due to flexibility, high porosity, good mechanical strength, high specific surface area, and flexible structures, while rGO nanoparticles were used to improve the detection sensitivity and anti-IGF-1 immobilizing. Different characterization techniques were applied consisting of FE-SEM, FT-IR, and EDS for the investigation of morphological features and nanofiber size. The redox reactions of [Fe(CN) 6 ] 4−/3− on the modified electrode surface were probed for studying the immobilization and determination processes, using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Under optimal conditions, LOD (limit of detection) and LOQ (limit of quantification) were obtained as 55.72 fg/mL and 185.73 fg/mL respectively, and sensitivity was acquired 136.29 μA/cm 2 .dec. Moreover, a wide linear range was obtained ranging from 1 pg/mL to 10 ng/mL for IGF-1. Furthermore, the proposed method was applied for the analysis of IGF-1 in several human plasma samples with acceptable results, and it also exhibited high selectivity, stability, and reproducibility.
研究领域:
生物医学工程
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分析化学
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材料科学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL BRAIN RESEARCH
·
2023
·Vol. 241
·期 6
·1661-1673
·
IF 2
Zhang Yuhe,Chen Yan,Yuan Shushu,Yu Qingxia,Fu Jianjiong,Chen Luyun,Liu Jiaming,He Yuping
Gastrodin (Gas) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of Gas against cognitive impairment via regulating gut microbiota. APPswe/PSEN1dE9 transgenic (APP/PS1) mice were treated intragastrically with Gas for 4 weeks, and then cognitive deficits, deposits of amyloid-β (Aβ) and phosphorylation of tau were analyzed. The expression levels of insulin-like growth factor-1 (IGF-1) pathway-related proteins, such as cAMP response element-binding protein (CREB), were detected. Meanwhile, gut microbiota composition was evaluated. Our results showed that Gas treatment significantly improved cognitive deficits and Aβ deposition in APP/PS1 mice. Moreover, Gas treatment increased the level of Bcl-2 and decreased level of Bax and ultimately inhibited neuronal apoptosis. Gas treatment markedly increased the expression levels of IGF-1 and CREB in APP/PS1 mice. Moreover, Gas treatment improved abnormal composition and structure of gut microbiota in APP/PS1 mice. These findings revealed that Gas actively participated in regulating the IGF-1 pathway to inhibit neuronal apoptosis via the gut–brain axis and that it can be considered a new therapeutic strategy against Alzheimer’s disease.
研究领域:
神经科学
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药理学
·
微生物学
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2019
·
IF 2.263
Yajing Pan,Chao Xiao,Huaping Tan,Guoliang Yuan,Jianliang Li,Shengke Li,Yang Jia,Dangsheng Xiong,Xiaohong Hu,Xiaohong Niu
Microspheres and injectable hydrogels derived from natural biopolymers have been extensively investigated as drug carriers and cell scaffolds. In this study, we report a preparation of composite scaffolds basing microspheres and hydrogel via the Schiff’s base reaction. Hybrid gelatin/heparin microspheres loading insulin-like growth factor-1 (IGF-1) with a diameter of 5–10 µm were fabricated using an emulsion cross-linking method. Synchronously, water-soluble carboxymethyl chitosan (CMC) and oxidized chondroitin sulfate (OCS) were prepared for cross-linking of hydrogels, which were embedded with microspheres to produce a composite microspheres/gel scaffold. The mechanism of scaffold cross-linking is attributed to the Schiff’s base reaction between amino and aldehyde groups of biopolymers. Currently, gelation rate, morphology, mechanical properties, swelling ratio, weight loss, and IGF-1 release of the composite scaffolds were examined in vitro. The results show that mechanical and bioactive properties of CMC-OCS hydrogel can be significantly improved by embedding gelatin/heparin microspheres containing IGF-1. Compressive modulus of composite gel scaffolds containing 3 wt% of microspheres was 16 kPa, which was higher than the control hydrogel without microspheres. Cumulative release of IGF-1 during 7 days from microspheres embedded hydrogel was 70%, which was significantly lower than those of microspheres and hydrogels. Moreover, the composite microspheres/gel scaffolds exhibited higher swelling ratio and slower degradation rate than the control. Potential of the composite scaffolds was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) in vitro. Cell culture showed that this composite hydrogel could support survival and proliferation of ASCs. These results demonstrate the potential of gelatin/heparin microspheres embedded CMC-OCS hydrogels as an injectable scaffold in soft tissue engineering.
研究领域:
组织工程
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生物材料科学
·
生物医学工程
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产品关联
DOI
高影响因子
Food Frontiers
·
2024
·
IF 7.4
Lu An,Wenbo Wang,Jihao Chu,Lin An,Bingyu Geng,Xueqi Fu,Jing Chen,Junfeng Ma
Alzheimer's disease (AD) poses a significant global health challenge, primarily characterized by the aggregation of β-amyloid (Aβ) peptides and associated oxidative stress. Given the lack of effective AD drugs, we investigated the effects of Lycium barbarum polysaccharide (LBP), a water-soluble polysaccharide from goji berries, on Aβ scavenging, aggregation, and Aβ-induced toxicity using the transgenic AD nematode. LBP treatment delayed paralysis, mitigated Aβ-induced chemotaxis deficits, and reduced Aβ 1–42 deposition and oligomer formation in AD nematodes. Furthermore, LBP supplementation alleviated Aβ-induced oxidative stress and improved oxidative stress resistance through the insulin/insulin growth factor 1 (IGF-1) signaling (IIS) pathway. Evaluation of the Aβ clearance pathway revealed that LBP attenuated Aβ toxicity by increasing proteasome activity rather than lysosomal levels. Basic physiological assessments further indicated that LBP was non-toxic in vivo and promoted nematode health. Our findings suggest that LBP ameliorates AD-like symptoms in nematodes by activating the IIS pathway to reduce oxidative stress and enhancing proteasomal activity to clear Aβ aggregates, providing a new theoretical basis for considering LBP as a promising therapeutic drug for AD and related oxidative stress complications.
研究领域:
神经科学
·
药理学
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分子生物学
·
老年医学
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Zhentao Man,Xiaoqing Hu,Zhenlong Liu,Hongjie Huang,Qingyang Meng,Xin Zhang,Linghui Dai,Jiying Zhang,Xin Fu,Xiaoning Duan,Chunyan Zhou,Yingfang Ao
Cartilage tissue engineering is the hotspot of cartilage repair. The allogenic chondrocytes appear to be a promising source of seed cells in cartilage tissue engineering. In this study, we aimed to transplant allogenic chondrocytes with chitosan hydrogel (CS)-demineralized bone matrix (DBM) hybrid scaffold (CS/DBM) to repair rabbit cartilage injury with one-step operation. After the CS/DBM scaffold was successfully fabricated, it showed that the porous CS filled the large pores of DBM, which improved the distribution of seed cells in the CS/DBM scaffold. The allogenic chondrocytes at second passage were transplanted with different scaffolds to repair rabbit cartilage injury. Twenty-four weeks after surgery, the cartilage defect in the CS/DBM group was successfully filled as shown by MRI. Moreover, the histological score of CS/DBM group was significantly higher than that of the other groups. On the aspect of biomechanical property , the regenerated cartilage in the CS/DBM group were superior to those in the other groups as determined by nanoindentation . Meanwhile, no obvious inflammatory response was observed after the transplantation of allogenic chondrocytes at 24 weeks post-surgery. Furtherly, gene expression profile for cells within the repair tissue was compared with the allogenic chondrocytes before transplantation using Agilent microarray and RT-qPCR. The results showed that some genes beneficial to cartilage regeneration, such as BMP-7, HGF , and IGF-1, were upregulated one month after transplantation. Consequently, our study demonstrated that the transplantation of allogenic chondrocytes with CS/DBM scaffold successfully repaired rabbit cartilage injury with only one-step operation, thereby providing new insights into cartilage tissue engineering.
研究领域:
组织工程
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骨科
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生物医学工程
✓ 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）