CARBOHYDRATE POLYMERS
·
2026
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IF 13.2
Jia-Mei Geng,Pei-Feng Zhu,Lu-Shuang Xu,Ji-Lai Liu,Zheng-Qing Yang,Zhu-Ya Yang,Qiong Jin,Lu Liu
The medicinal moss Rhodobryum giganteum is rich in polysaccharides, whose structural and biofunctional properties remain largely unexplored. In this study, a novel glucose-rich polysaccharide fraction (named RGP, 29.8 kDa) was isolated and characterized from R. giganteum . Structural analysis revealed a unique α -1,6-linked glucan backbone with C-2 acetylation, along with side chains composed of →4)- α - d -glucopyranosyl-(1 → and terminal α - d -glucopyranose units. RGP significantly promoted proliferation, phagocytosis, and cytokine (TNF- α , IL-6) secretion via the TLR4/PI3K-Akt/IκB α pathway in RAW264.7 cells. In immunosuppressed mice, RGP restored immune function, as shown by improved organ indices, elevated serum immunoglobulins (IgA, IgG, IgM), and alleviated splenic damage. Molecular docking revealed that RGP binds the hydrophobic pocket of the TLR4/PI3K-Akt/IκB α complex via its glucose chain, and dynamics simulations confirmed the stability of this interaction. These findings reveal the bioactivity of bryophyte polysaccharides and suggest RGP as a potential immunomodulatory agent.
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PLATELETS
·
2026
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IF 3.1
Shaochuan Wang,Debin Guo,Shidan Li,Ruohui Tang,Hao Jiang,Xiaoming Li,Youbin Li,Jing Yang,Lei Li,Jun Fei
Bone maintains a dynamic and stable state through the orchestration of osteoclasts and osteoblasts. Osteoblasts are derived mainly from mesenchymal stem cell (MSC) and are responsible for bone formation. The inhibition of osteoblast proliferation and differentiation is involved in many diseases, including osteoporosis, osteoarthritis, infected bone defects, and inflammatory aseptic loosening of implants. Given the currently limited treatment options, exploring new methods to promote bone formation is an important focus significant for orthopedists. Platelet-rich plasma (PRP), an autologous substance that is rich in various growth factors, is widely used in regenerative medicine. However, the effect of PRP on inflammatory bone destruction remains unclear. We investigated the effects of PRP on the viability of MSC, and the impact of different concentrations of PRP (1% and 3%, respectively) on cell death, proliferation, and differentiation. Furthermore, we tested the therapeutic effect of different concentrations of PRP (1% and 3%) on LPS-induced inflammatory bone destruction in vivo. PRP enhanced the cellular activity of MSC and promoted osteogenesis. A higher concentration of PRP (3%) primarily reduced the death and increased the proliferation of in LPS-treated MSC via the PI3K/AKT pathway, while a lower concentration of PRP (1%) promoted MSC differentiation into osteoblasts through the MAPK pathway. Consistent with in vitro experiments, we validated the protective effect of PRP against LPS-induced bone loss by increasing bone formation in vivo. These results suggest that different concentrations of PRP can ameliorate LPS-induced inflammatory bone loss through distinct mechanisms.
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ANNALS OF CLINICAL AND LABORATORY SCIENCE
·
2022
·Vol. 52
·期 1
·48-59
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IF 1.18
Guomin Lv,Yan Chen,Zhengyue Cheng,Lixiang Lin,Huasong Shen
Objective Osteoporosis is likely becoming a new disease challenge with increasing aging population. Circ_0006873 dysregulation mayserve as an event linked to osteoporosis. Thus, this study sought to evaluate the function and mechanism of circ_0006873 onosteoporosis. Methods Clinical serum samples collected from 30 osteoporosis patients were utilized to obtain circ_0006873 and miR-142-5p expressiondata. The link between circ_0006873, miR-142-5p, and phosphatase and tensin homolog (PTEN) was demonstrated via online tools(starBase, circinteractome), RNA Immunoprecipitation (RIP) and dual-Luciferase reporter assays. After knockdown or overexpression,cell counting kit-8 (CCK-8) assay measured cell viability. Alizarin red S (ARS) staining as well Alkaline phosphatase (ALP)staining detected osteoblastic differentiation levels. Quantitative real-time PCR (qRT-PCR) and western blot analyzed expressionof RNAs and proteins after transfection or during osteoblastic differentiation. Results circ_0006873 was upregulated in osteoporosis patients and decreased during osteoblastic differentiation. Following experimentsrevealed that cell viability, proliferation-related factors, osteogenic marker genes (ALP, Runx2, Bglap) and osteoblasticdifferentiation degree were promoted after circ_0006873 knockdown but inhibited after overexpression. Circ_0006873 spongedmiR-142-5p, which was downregulated in osteoporosis patients and became higher during osteoblastic differentiation. Rescueassay indicated miR-142-5p mimic could reverse the effects of circ_0006873 overexpression on cell viability and osteogenicmarkers, and also could activate Akt pathway. Furthermore, circ_0006873 can negatively target miR-142-5p via regulating PTENto inhibit osteoblastic differentiation. Conclusion Circ_0006873 sponges miR-142-5p thereby enhances PTEN expression to suppress osteoblastic differentiation via regulationof Akt signaling pathway, thus, may provide a treatment approach for osteoporosis.
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ALLERGOLOGY INTERNATIONAL
·
2025
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IF 6.7
Maoxin Huang,Liping Dong,Yue He,Xinying Cai,Yun Lu,Jinlei Xu,Fengli Xiao
Background YTHDF1, a critical regulator of cellular processes, has attracted attention for its involvement in some inflammatory diseases. However, its specific association with atopic dermatitis (AD) remains unclear. The objective is to investigate the functional roles and underlying mechanisms of YTHDF1 in AD. Methods The expression of YTHDF1 was investigated by bioinformatics analysis and skin lesions of AD patients. The functional role and upstream and downstream regulatory mechanisms of YTHDF1 were examined through a series of in vitro and in vivo experiments. Adeno-associated virus (AAV)-mediated delivery of YTHDF1 in the AD mouse model was evaluated for its therapeutic potential. Results Bioinformatics analysis revealed that the YTHDF1 mRNA level in the skin lesions of AD was significantly higher than that in healthy people. YTHDF1 expression was significantly elevated in AD skin lesions, the DNCB-induced AD mouse model, and primary human keratinocytes and HaCaT cells stimulated with interleukin (IL)-4/IL-13, compared to controls. Both in vitro and in vivo experiments revealed that upregulation of YTHDF1 in AD exacerbated cell proliferation and inhibited keratinization by activating the PI3K/AKT pathway, which was modulated via the IL-4/IL-13/STAT3 axis. Moreover, topical application of AAV-YTHDF1 significantly improved AD-like lesions in the mouse model. Conclusions This study identifies YTHDF1 as a contributor to AD pathogenesis by influencing keratinocyte proliferation and differentiation. It also suggests that YTHDF1 could be a potential therapeutic target for AD treatment.
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Drug Design Development and Therapy
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2022
·
IF 4.319
Yu Li,Ximei Wang
Purpose High glucose environment in diabetes mellitus induces the dysfunction of bone marrow-derived mesenchymal stromal cells (BMSCs) and impairs bone regeneration. Chrysin is a natural polyphenol with outstanding anti-inflammation and anti-oxidation ability. However, whether and how chrysin affects BMSCs in high glucose conditions remain poorly understood. The present study aimed to explore the effects and underlying mechanisms of chrysin on the BMSCs exposed to high glucose environment.Materials and Methods Cell viability was detected by cell counting kit 8 assay and 5-ethynyl-2’-deoxyuridine staining, while cell apoptosis was determined through flow cytometry using Annexin V-FITC/PI kit. The oxidative stress in BMSCs was evaluated by detecting the reactive oxygen species production, malondialdehyde content, and superoxide dismutase activity. Alkaline phosphatase staining, Alizarin Red staining, and quantitative real-time PCR were performed to determine the osteogenic differentiation. Western blot was used to examine the expression of the PI3K/ATK/Nrf2 signaling pathway. Furthermore, chrysin was injected into calvarial defects of type 1 diabetic SD rats to assess its in vivo bone formation capability.Results Chrysin reduced oxidative stress, increased cell viability, and promoted osteogenic differentiation in BMSCs exposed to high glucose. Blocking PI3K/ATK/Nrf2 signaling pathway weakened the beneficial effects of chrysin, indicating that chrysin at least partly worked through the PI3K/ATK/Nrf2 pathway.Conclusion Chrysin can protect BMSCs from high glucose-induced oxidative stress via the activation of the PI3K/AKT/Nrf2 pathway, and promote bone regeneration in type 1 diabetic rats.
研究领域:
细胞生物学
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分子生物学
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糖尿病研究
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Nanoscience and Nanotechnology Letters
·
2020
·Vol. 12
·期 6
·774-781
·
IF 1.128
Su Fanfan,Guo Ming,Wang Jinhua
Using nanomaterials is a potential way to improve the accuracy and safety of chemotherapeutic drugs and avoid the toxic side effects caused by the non-selectivity of traditionally used chemotherapeutic agents. Vincristine is a commercial clinical chemotherapeutic drug with good anti-tumor
effects. However, the effects of vincristine decorated hybrid nanoparticles (VCR-HNPs) on human retinoblastoma cells have not been previously reported. In this study, we explored the impact of VCR-HNPs exposure on retinoblastoma cells and identified the corresponding mechanism involved in
their activity. Retinoblastoma WERI-Rb1 and Y-79 cell lines were treated with different concentrations of VCR-HNPs and effects on cell proliferation were analyzed using the CCK8 assay, while apoptosis was measured and analyzed by flow cytometry. To further analyze the outcome of apoptosis,
Western blot assay was used to evaluate the expression levels of proteins correlating with apoptosis. Proteins involved in the PI3K/Akt pathway were also analyzed by western blotting to identify whether this pathway was involved in the molecular response to VCR-HNPs exposure. Compared with
the control group, VCR-HNPs markedly inhibited cell proliferation and induced apoptosis, at concentrations greater than 20 mg/L. In addition, western blotting experiments confirmed that VCR-HNPs could downregulate the phosphorylation of proteins involved in the PI3K/Akt signaling pathway leading
to the inactivation of the signaling pathway. VCR-HNPs exerted tumor suppressor effects on human retinoblastoma via inhibition of the PI3K/Akt signaling pathway.
研究领域:
肿瘤学
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纳米医学
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分子生物学
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DISEASE MARKERS
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2022
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IF 3.464
Zhiwen Wang,Changfeng Wang,Jieping Fu,Ruen Liu,Xinhui Zhou
Purpose. Cinnamaldehyde (CA) is the main ingredient in cinnamon, and it has been proven to have an inhibitory effect on many different tumor types. However, it lacks effect on glioma. This paper explores the effect CA has on glioma cells U87 and U251 at the cellular and molecular levels. Methods. The relationship between Hif-1α and Sept9 was found by CGGA. Cell Viability Assay (CCK8) was made to detect the proliferation ability. The scratch experiment and the transwell experiment were applied to the migration and invasion ability. Annexin V-FITC/PI were used to detect the cell apoptosis. Western blotting was used to determine the specified protein level. Results. Cell proliferation assay results revealed CA to inhibit the proliferation of glioma cells in a dose-dependent manner. It promoted apoptosis for upregulating the expression of Bax and downregulating the expression of Bcl-2. Wound Healing Assay and transwell test found CA to have anti-invasion ability and that it upregulated the expression of E-cadherin and downregulated the expressions of MMP-2 and MMP-9. The molecular mechanism was studied from a tumor microenvironment (TME) perspective. Pi3k inhibitor (LY294002) was used for interfering with cells, and the results found CA to demonstrate a similar effect. Hif-1α and Sept9 expressions were inhibited, and Akt and p-Akt were also inhibited. By using CoCl2 to make hypoxia, CA was discovered to inhibit the high expression of Hif-1α and Sept9, demonstrating a correlation with the Pi3k/Akt pathway. It is suggested that the mechanism of Sept9 under hypoxia regulation can be realized through the Pi3k/Akt pathway. Conclusions. This study proves for the first time that CA is an effective drug for inhibiting the proliferation of glioma through Sept9 and reveals Sept9 to be related to the Pi3k/Akt pathway in terms of tumor microenvironment, providing a molecular basis for the further study of CA in glioma treatment.
研究领域:
肿瘤学
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分子生物学
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药理学
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EXPERIMENTAL CELL RESEARCH
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2021
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IF 3.905
Decai Chi,Dong Wang,Minghui Zhang,Hui Ma,Fuhui Chen,Yajiao Sun
Lung cancer is the leading cause of cancer mortality worldwide. CLEC12B , a C-type lectin-like receptor, is low-expressed in lung cancer tissues. However, the function of CLEC12B in lung cancer and its underlying mechanism remain unclear. Here, an obvious down-regulation of CLEC12B was observed in lung cancer cells compared with the normal lung epithelial cells. CLEC12B over-expression suppressed cell viability and cell cycle entry in lung cancer, along with the reduction of PCNA and cyclin D1 expressions, while silencing CLEC12B possessed the opposite effects. Over-expression of CLEC12B promoted lung cancer cell apoptosis, accompanied by decreased Bcl-2 and increased Bax, cleaved caspase-3 and cleaved caspase-9. Moreover, CLEC12B decreased phosphorylation of PI3K-p85 and AKT proteins. By contrast, CLEC12B knockdown activated the PI3K/AKT pathway. In vivo , CLEC12B inhibited tumor growth in lung cancer, which can be reversed by CLEC12B inhibition. Co-IP and immunofluorescence assays confirmed the interaction between CLEC12B and SHP-1, and CLEC12B over-expression increased SHP-1 level. Furthermore, knocking down SHP-1 abrogated the above biological phenotypes caused by CLEC12B elevation. Taken together, our findings demonstrate that CLEC12B serves as a tumor-suppressing gene in lung cancer through positively regulating SHP-1 expression, which may be mediated by the PI3K/AKT signaling pathway .
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED
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2023
·
IF 2.5
Fangyuan Lai,Shijie Dai,Ye Zhao,Yi Sun
Adipose-derived stem cells (ADSCs) have been widely proven to facilitate wound healing. Our study aimed to estimate the influence of combined ADSCs and platelet-derived growth factor-BB (PDGF-BB) on wound healing. We utilized 4 healthy SD rats to isolate ADSCs. Platelet-rich plasma (PRP) was acquired utilizing a two-step centrifugation technology. The role of PRP, PDGF-BB, and PDGF-BB combined with a PI3k inhibitor LY294002 on the viability, migration, and PTEN/AKT pathway in ADSCs were examined utilizing CCK-8, Transwell, and western blot assays. Then, we constructed an open trauma model in SD rats. Effects of ADSCs treated with PDGF-BB on pathological changes, CD31, and PTEN/AKT pathway of wound closure were assessed by hematoxylin & eosin (H&E) staining, Masson staining, immunohistochemical, and western blot assays, respectively. PRP and PDGF-BB intensified the viability and migration of ADSCs by modulating the PTEN/AKT pathway. Interestingly, LY294002 reversed the role of PDGF-BB on ADSCs. In vivo experiments, combined intervention with ADSCs plus PDGF-BB/PRP facilitated wound closure and ameliorated histological injury. Moreover, combined intervention with ADSCs and PDGF-BB attenuated the PTEN level and elevated the CD31 level as well as the ratio of p-AKT/AKT in the skin tissues. A combination of ADSCs and PDGF-BB facilitated wound healing might associate with the regulation of the PTEN/AKT pathway.
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BONE
·
2022
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IF 4.626
Abdusami Abdurahman,Xinle Li,Jie Li,Daquan Liu,Lidong Zhai,Xuetong Wang,Yifan Zhang,Yao Meng,Hiroki Yokota,Ping Zhang
Bone vasculature influences osteogenesis and haematopoiesis in the bone microenviroment. Mechanical loading has been shown to stimulate the formation of osteogenesis-related type H vessels in an ovariectomy (OVX)-induced osteoporosis mouse model. To determine the loading-driven mechanism of angiogenesis and the formation of type H vessels in bone, we evaluated the roles of PI3K/Akt signaling and erythropoiesis in the bone marrow . The daily application of mechanical loading (1 N at 5 Hz for 6 min/day) for 2 weeks on OVX mice inhibited osteoclast activity , associated with an increase in the number of osteoblasts and trabecular volume ratio. Mechanical loading enhanced bone vasculature and vessel formation, as well as PI3K/Akt phosphorylation and erythropoiesis in the bone marrow. Notably, LY294002 , an inhibitor of PI3K signaling, blocked the tube formation by endothelial progenitor cells , as well as their migration and wound healing. The conditioned medium, derived from erythroblasts , also promoted the function of HUVECs with elevated levels of VEGF, CD31 , and Emcn. Collectively, this study demonstrates that mechanical loading prevents osteoporotic bone loss by promoting angiogenesis and type H vessel formation. This load-driven preventing effect is in part mediated by PI3K/Akt signaling and erythropoiesis in the bone marrow.
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Drug Design Development and Therapy
·
2022
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IF 4.319
Lei Lei,Jing Zhao,Xue-Qi Liu,Juan Chen,Xiang-Ming Qi,Ling-Ling Xia,Yong-Gui Wu
Introduction Kidney tubular epithelial injury is one of the key factors in the progression of diabetic nephropathy (DN). Wogonin is a kind of flavonoid, which has many pharmacological effects, such as anti-inflammation, anti-oxidation and anti-fibrosis. However, the effect of wogonin in renal tubular epithelial cells during DN is still unknown.Materials and Methods STZ-induced diabetic mice were given doses of wogonin (10, 20, and 40 mg/kg) by intragastric administration for 16 weeks. The metabolic indexes from blood and urine and pathological damage of renal tubules in mice were evaluated. Human tubular epithelial cells (HK-2) were cultured in high glucose (HG) condition containing wogonin (2μM, 4μM, 8μM) for 24 h. Tubular epithelial cell inflammation and autophagic dysfunction both in vivo and in vitro were assessed by Western blot, qRT-PCR, IHC, and IF analyses.Results The treatment of wogonin attenuated urinary albumin and histopathological damage in tubulointerstitium of diabetic mice. We also found that wogonin down-regulated the expression of pro-inflammatory cytokines and autophagic dysfunction in vivo and in vitro. Molecular docking and Cellular Thermal Shift Assay (CETSA) results revealed that mechanistically phosphoinositide 3-kinase (PI3K) was the target of wogonin. We then found that inhibiting PI3K eliminated the protective effect of wogonin. Wogonin regulated autophagy and inflammation via targeting PI3K, the important connection point of PI3K/Akt/NF-κB signaling pathway.Conclusion Our study is the first to demonstrate the novel role of wogonin in mitigating tubulointerstitial fibrosis and renal tubular cell injury via regulating PI3K/Akt/NF-κB signaling pathway-mediated autophagy and inflammation. Wogonin might be a latent remedial drug against tubular epithelial injury in DN by targeting PI3K.
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Chinese Medicine
·
2022
·Vol. 17
·期 1
·1-21
·
IF 4.546
Huang Qianqian,Zhang Chen,Dong Shi,Han Junwen,Qu Sihao,Xie Tianshu,Zhao Haibin,Shi Yuanyuan
Background Alzheimer's Disease (AD) is a serious neurodegenerative disease and there is currently no effective treatment for AD progression. The use of TCM as a potential treatment strategy for AD is an evolving field of investigation. Asafoetida (ASF), an oleo-gum-resin isolated from Ferula assa-foetida root, has been proven to possess antioxidative potential and neuroprotective effects, which is closely associated with the neurological disorders. However, the efficacy and further mechanisms of ASF in AD experimental models are still unclear. Methods A cognitive impairment of mouse model induced by scopolamine was established to determine the neuroprotective effects of ASF in vivo , as shown by behavioral tests, biochemical assays, Nissl staining, TUNEL staining, Immunohistochemistry, western blot and qPCR. Furthermore, the PC12 cells stimulated by H 2 O 2 were applied to explore the underlying mechanisms of ASF-mediated efficacy. Then, the UPLCM analysis and integrated network pharmacology approach was utilized to identified the main constitutes of ASF and the potential target of ASF against AD, respectively. And the main identified targets were validated in vitro by western blot, qPCR and immunofluorescence staining. Results In vivo , ASF treatment significantly ameliorated cognitive impairment induced by scopolamine, as evidenced by improving learning and memory abilities, and reducing neuronal injury, cholinergic system impairment, oxidative stress and apoptosis in the hippocampus of mice. In vitro , our results validated that ASF can dose-dependently attenuated H 2 O 2 -induced pathological oxidative stress in PC12 cells by inhibiting ROS and MDA production, as well as promoting the activities of SOD, CAT, GSH. We also found that ASF can significantly suppressed the apoptosis rate of PC12 cells increased by H 2 O 2 exposure, which was confirmed by flow cytometry analysis. Moreover, treatment with ASF obviously attenuated H 2 O 2 -induced increase in caspase-3 and Bax expression levels, as well as decrease in Bcl-2 protein expression. KEGG enrichment analysis indicated that the PI3K/Akt/GSK3β/Nrf2 /HO-1pathway may be involved in the regulation of cognitive impairment by ASF. The results of western blot, qPCR and immunofluorescence staining of vitro assay proved it. Conclusions Collectively, our work first uncovered the significant neuroprotective effect of ASF in treating AD in vivo . Then, we processed a series of vitro experiments to clarify the biological mechanism action. These data demonstrate that ASF can inhibit oxidative stress induced neuronal apoptosis to foster the prevention of AD both in vivo and in vitro , and it may exert the function of inhibiting AD through PI3K/Akt/GSK3β/Nrf2/HO-1pathway.
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