CELLULAR AND MOLECULAR LIFE SCIENCES
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2025
·Vol. 82
·期 1
·1-16
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IF 6.2
Du Li,Cui Yinghong,Chen Wei,Li Chunyun,He Zuping
Sertoli cell-only syndrome (SCOS) is one of the most severe non-obstructive azoospermia (NOA) types, since only Sertoli cells with not any male germ cells exist with the seminiferous tubules. As such, it is of particular significance to elucidate molecular mechanisms underlying SCOS for improving the diagnosis and treatment strategies for this disease. Due to the difficulties in obtaining sufficient human testicular tissues and the limited availability of human cells, the traditional proteomics is inadequate for comparing the differences in large scale of protein expression patterns of human Sertoli cells between SCOS and normal men. To solve this issue on the requirement of large amount of cell numbers, we employed micro-proteomics to reveal distinct global protein expression profiles of human Sertoli cells between SCOS and obstructive azoospermia (OA) with normal spermatogenesis utilizing single human Sertoli cells. We found a significant downregulation of proteins involved in cell adhesion pathways in SCOS Sertoli cells, whereas proteins related to apoptosis were markedly upregulated. Interestingly, we identified the lower expression of SPARC (secreted protein acidic and rich in cysteine) and the higher expression of FGF2 (fibroblast growth factor 2) in human Sertoli cells of the SCOS compared to normal men. SPARC silencing led to upregulation of FGF2 in human Sertoli cells, and SPARC may be associated with the occurrence of SCOS and serves as a reliable marker for the diagnosis of this disease. This study thus comprehensively offers the proteomic landscape of human Sertoli cells in the testes of SCOS patients and it sheds a novel insight into the pathogenesis of SCOS.
研究领域:
生殖生物学
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分子医学
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2019
·Vol. 10
·期 9
·6009-6019
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IF 3.241
Yun Yu,Xiu-Yuan Lang,Xi-Xi Li,Run-Ze Gu,Qing-Shan Liu,Rongfeng Lan,Xiao-Yan Qin
The major bioactive ingredient THSG of Polygonum multiflorum is well established for its anti-oxidation, anti-aging and anti-inflammation properties. Increasing evidence supports the capacity of THSG to ameliorate the biochemistry of neurotrophins and their downstream signaling axis in mouse models to attenuate neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this study, the neuroprotective effects of THSG were studied in vitro and in vivo. In cultured mesencephalic dopamine neurons and SH-SY5Y cell line, it was found that THSG protected the integrity of the cell body and neurite branching from MPP+-induced toxicity by restoring the expression of FGF2 and BDNF and their downstream signaling pathways to inhibit apoptosis and promote cell survival. The inhibition of Akt signaling by LY294002 or TrkB activity by K252a eliminated the neuroprotective effects of THSG. In the MPTP-induced mouse models of Parkinson's disease, THSG ameliorated the animal behaviors against MPTP-induced neurotoxicity, which was demonstrated by the pole test and the tail suspension test. Biochemical and immunohistochemical analysis verified the THSG-mediated restoration of the FGF2-Akt and BDNF-TrkB signaling axis in the substantia nigra and corpus striatum and the recovery of dopaminergic neurons. These results establish the neuroprotective effects of THSG in vitro and in vivo and unravel the underlying mechanism against toxin-induced neural atrophy, providing a new avenue for the use and pharmacological research of edible medicine for anti-neurodegenerative diseases.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2026
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IF 7.8
Muyaxin Wang,Wenliang Xue,Jinyu Liu,Yuhao Jiang,Jianhong Luo,Shasha Shi,Xudong Yin,Xinsong Li
Diabetic foot ulcer (DFU) is a severe complication of diabetes, characterized by impaired healing due to chronic inflammation, poor blood vessel growth, and compromised cell function. To improve DFU healing, we create a FGF2 mRNA loaded liposome/exosome hybrid (FGF2-LEH) with dual functions of tissue regrowth and inflammation regulation. The FGF2-LEH was fabricated by incubating FGF2 mRNA with liposomes to form the FGF2-Lipo complex, followed by hybridization with platelet-rich plasma-derived exosomes (PRP-Exos) through freeze–thaw cycle and extrusion. Characterizations demonstrated that the FGF2-LEH had suitable particle size, high encapsulation efficiency, and biosafety. In vitro experiments revealed that FGF2-LEH enhanced the migration and tube formation of human umbilical vein endothelial cells, highlighting its pro-angiogenic potential. In both type 1 and type 2 diabetic mouse models, a single dose of FGF2-LEH greatly accelerated wound healing. After 15 days, the healing rate of the FGF2-LEH group exceeded 96% with improved granulation tissue growth, which was superior to that of control. Histopathological analysis further confirmed that FGF2-LEH promoted CD31+ angiogenesis, increased collagen deposition, and induced macrophages toward M2 polarization, thereby improving anti-inflammatory effect. Taken together, FGF2-LEH combining the advantages of PRP-Exos and FGF2 mRNA provides an approach for DFU treatment with translational potential for clinical application.
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DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Ya-wei Zhang,Xiaoyang Pang,Yan Yang
Background A new spray adhesive (KYNA-PF127) was established through the combination of thermosensitive hydrogel (Pluronic F127) and KYNA, aimed to investigate the effect of KYNA-PF127 on multi-territory perforator flaps and its possible molecular mechanism. Materials and methods 36 SD male rats with 250–300 g were randomly divided into 3 groups (n = 12): control group, blank glue group and KYNA-PF127 group. KYNA-PF127 hydrogel was prepared and characterized for its morphology and properties using scanning electron microscopy. CCK-8 assay, scratch wound assay, transwell assay, tube formation assay and Ki67 staining were used to study the effect of KYNA-PF127 on the proliferation, migration, and tube formation of HUVECs. VEGF and FGF2 were measured by qPCR to evaluate the angiogenesis capacity of HUVECs in vitro. In vivo, the effect of each group on the survival area of the cross-zone perforator flap was evaluated, and angiogenesis was evaluated by HE and immunofluorescence (CD31 and MMP-9). The effect of inflammation on skin collagen fibers was assessed by Masson. Immunohistochemistry (SOD1, IL-1β, TNF-α) was used to evaluate the effects of oxidative stress and inflammatory factors on multi-territory flaps. Results KYNA-PF127 has good sustained release and biocompatibility at 25% concentration. KYNA-PF127 promoted the proliferation, migration, and angiogenesis of HUVECs in vitro. In vivo, the survival area of multi-territory perforator flaps and angiogenic capability have increased after KYNA-PF127 intervention. KYNA-PF127 could effectively reduce the oxidative stress and inflammation of multi-territory perforator flaps. Conclusion KYNA-PF127 promotes angiogenesis through its antioxidant stress and anti-inflammatory effects, and shows potential clinical value in promoting the survival viability and drug delivery of multi-territory perforator flaps.
研究领域:
生物医学工程
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组织工程
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药学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Xi-Xi Li,Xiu-Yuan Lang,Teng-Teng Ren,Jun Wang,Rongfeng Lan,Xiao-Yan Qin
Ethnopharmacological relevance Tibetan ginseng named Wangla (tuber of Coeloglossum viride var. bracteatum ) is a traditional tonic that has Yang-strengthening and qi-enhancing, tranquilizing, intelligence-enhancing and longevity-enhancing properties. It has been used to treat impotence, spermatorrhea , anemia and insomnia. Therefore, its characteristic components and neuronal modulating effects were studied. Aim of the study: To investigate the elimination of Aβ-induced toxicity by CE and to elucidate the molecular mechanisms involving BDNF , FGF2 , and their related signaling axis, and the RIP1-driven inflammatory pathway. Materials and methods We established Aβ-induced toxicity models in cultured neurons and ICR mice , respectively. MWM and fear conditioning tests were performed for behavioral analysis of cognitive functions in mice. Western blot was used to investigate the levels of BDNF, FGF2, and their downstream effector TrkB/Akt/Bcl-2, as well as the RIP1-driven RIP1/RIP3/MLKL pathway. Immunofluorescence assay is used to examine the status of glial cells. Results CE abrogated Aβ toxicity and inhibited apoptosis in cultured neurons, mainly by regulating the BDNF, FGF2, and TrkB/Akt signaling pathways as well as RIP1-driven inflammation and necroptosis. Similarly, mice injected intracerebrally with Aβ exhibited cognitive deficits and had elevated oxidative stress and inflammatory factors detected in their serum and brain. However, CE-treated mice showed recovery of cognitive abilities and quelled levels of oxidative stress and inflammatory factors. Moreover, Aβ toxicity led to a reduction in BDNF, FGF2, and related signaling regulators in the hippocampus and prefrontal cortex, accompanied by activation of RIP1-driven inflammatory signaling pathways, and a reduction in TBK1 and Bcl-2. However, CE restored the levels of BDNF, FGF2, and TrkB/Akt signaling pathway, while inhibiting RIP1-induced RIP1/RIP3/MLKL pathway, thereby antagonizing apoptosis and maintaining neuronal activity. Conclusions CE effectively eliminated the toxicity of Aβ in cultured neurons and mouse models, which holds promise for drug development .
研究领域:
神经药理学
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民族药理学
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分子生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
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2024
·Vol. 21
·期 1
·1-16
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IF 9.3
Chen Lushu,Zhang HuiYing,Zhang Ying,Li Xiumiao,Wang MeiHuan,Shen Yaming,Cao Yuan,Xu Yong,Yao Jin
Retinal neovascularisation is a major cause of blindness in patients with proliferative diabetic retinopathy (PDR). It is mediated by the complex interaction between dysfunctional ganglion cells, microglia, and vascular endothelial cells. Notably, retinal microglia, the intrinsic immune cells of the retina, play a crucial role in the pathogenesis of retinopathy. In this study, we found that lysophosphatidylserines (LysoPS) released from injured ganglion cells induced microglial extracellular trap formation and retinal neovascularisation. Mechanistically, LysoPS activated the GPR34-PI3K-AKT-NINJ1 signalling axis by interacting with the GPR34 receptor on the microglia. This activation upregulated the expression of inflammatory cytokines, such as IL-6, IL-8, VEGFA, and FGF2, and facilitated retinal vascular endothelial cell angiogenesis. As a result, inhibition of the GPR34-PI3K-AKT-NINJ1 axis significantly decreased microglial extracellular trap formation and neovascularisation by suppressing LysoPS-induced microglial inflammatory responses, both in vitro and in vivo. This study reveals the crucial role of apoptotic ganglion cells in activating microglial inflammation in PDR, thereby enhancing our understanding of the pathogenesis of retinal neovascularisation.
研究领域:
眼科学
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免疫学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Arabian Journal of Chemistry
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2024
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IF 5.3
Dong Xie,Guangfu Lv,Yuchen Wang,Wenjing Zhang,Nian Li,Yao Duan,Qing Huang,Ge Chen,Zifeng Pi,Hao Yue
Tenghuang Jiangu Wan (THJGW) is a commonly utilized treatment for osteoarthritis (OA), yet its pharmacodynamic material basis and molecular mechanism remain inadequately understood. This study systematically characterized the in vitro and in vivo chemical components of THJGW using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The pharmacodynamic material basis of THJGW in the treatment of OA was explored through a target network pharmacology approach and molecular docking technology. Cellular experiments were subsequently employed to validate the molecular mechanisms. Consequently, a total of 134 components from THJGW were identified in vitro , comprising 45 flavonoids, 10 iridoid glycosides, 39 phenylethanoid glycosides, 9 phenylpropanoids, 11 organic acids, 4 phenolics, and 16 other compounds. Additionally, 38 prototype absorbed components in serum were characterized for the purpose of network construction. 11 key components and 10 core targets (VEGFA, STAT3, RELA/NF-κB p65, PIK3R1, PIK3CA, MMP9, MMP1, IL-6, HDAC1, and FGF2) were determined by the target network pharmacology. Through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it was found that these intersection targets are associated with various signaling pathways such as pathways in cancer, lipid and atherosclerosis, and prostate cancer. Notably, the lipid and atherosclerosis pathway was closely linked to OA. The molecular docking results demonstrated strong binding affinities of the three core targets: IL-6, STAT3, and RELA/NF-κB p65. These results suggest that these targets may play a significant role for THJGW in treating OA. In vitro experiments showed that THJGW had notable protective effects on LPS-induced RAW264.7 macrophages by reducing levels of TNF-α and IL-6, and inhibiting phosphorylation expression of STAT3 and NF-κB p65 proteins related to the lipid and atherosclerosis pathway. This study provides insight into the pharmacodynamic material basis and mechanism of action for THJGW in the treatment of OA, which provide scientific evidence for the scientific application and improvement of quality standards for THJGW.
研究领域:
药理学
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生物化学
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分子生物学
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中医药
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产品关联
DOI
高影响因子
Biomaterials Science
·
2020
·Vol. 9
·期 3
·882-891
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IF 6.183
Zecong Xiao,Xinyao Zheng,Ying An,Kangning Wang,Junwen Zhang,Huacheng He,Jiang Wu
Growth factors (GFs) have been well known for their therapeutic effects on wound healing. Due to their vulnerable biostability, biomaterial carriers are usually used to deliver GFs to maintain their bioactivity. Among the carriers, PEG hydrogels are the most widely applied. But the uncontrolled release of GFs and their immunogenicity dramatically retard the application of PEG hydrogels as carriers of GFs. Herein, FGF2 loaded zwitterionic sulfobetaine methacrylate (SBMA) hydrogels were developed, and it was revealed that these hydrogels were more effective in delivering FGF2 for wound healing than were PEG hydrogels. In vitro studies demonstrated that SBMA hydrogels could successfully prolong the release of FGF2, which effectively maintained the bioactivity of FGF2. Further in vivo investigation showed that SBMA hydrogels could efficiently accelerate wound regeneration by promoting granulation tissue formation, collagen deposition, cell proliferation and migration, reepithelialization and angiogenesis. All results validated that SBMA hydrogels were promising substituents of PEG hydrogels for delivering FGF2 for wound regeneration.
研究领域:
生物材料
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组织工程
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伤口愈合
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药物递送系统
✓ 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）