CURRENT PHARMACEUTICAL BIOTECHNOLOGY
·
2021
·Vol. 22
·期 5
·609-621
·
IF 2.837
Zheng Jing,Changyuan Wang,Shijie Wen,Yue Jin,Qiang Meng,Qi Liu,Jingjing Wu,Huijun Sun,Mozhen Liu
Background: Osteoporosis, characterized by bone loss, usually occurs with the increased bone resorption and decreased bone formation. H2O2-induced MC3T3-E1 cells are commonly used for the study of osteoblastic activities, which play a crucial role in bone formation. Objective: This study aimed to investigate the effects of Phosphocreatine (PCr) on the osteoblastic activities in H2O2-induced MC3T3-E1 cells and elaborate on the possible molecular mechanism. Methods: The Osteoprotegerin (OPG)/Receptor Activator of NF-ΚB Ligand (RANKL) ratio and osteogenic markers were detected to investigate the effects of PCr on osteoblastic activities, and the osteoblastic apoptosis was detected using Hochest staining. Moreover, oxidative stress, Adenosine Triphosphate (ATP) generation and the expression of Sirtuin 1 (SIRT1), Forkhead Box O 1 (FOXO1) and Peroxisome Proliferator-Activated Receptor Γ Coactivator-1α (PGC-1α) were also examined to uncover the possible molecular mechanism in H2O2-induced MC3T3-E1 cells. Result: The results showed that PCr promoted the osteoblastic differentiation by increasing the expression levels of osteogenic markers of Alkaline Phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as increased the OPG/RANKL ratio and suppressed the osteoblastic apoptosis in H2O2-induced MC3T3-E1 cells. Moreover, treatment with PCr suppressed reactive oxygen species (ROS) over-generation and promoted the ATP production as well as increased the PGC-1α, FOXO1 and SIRT1 protein expression levels in H2O2-induced MC3T3-E1 cells. Conclusion: PCr treatment could promote osteoblastic activities via suppressing oxidative stress and increasing the ATP generation in H2O2-induced MC3T3-E1 cells. In addition, the positive effects of PCr on osteoblasts might be regulated by SIRT1/FOXO1/ PGC-1α signaling pathway.
研究领域:
医学
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分子生物学
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DOI
高影响因子
Frontiers in Pharmacology
·
2026
·
IF 5.4
Yihuang Liu,Xiaofeng Li,Xia Zhang,Hua Cao,Nailin Zhang,Jianhui Sun,Pingping Chen
Introduction This research sought to investigate the therapeutic efficacy and underlying mechanisms of Shengjiang Powder (SJP) in the context of chronic gastritis. Methods A rat model of gastric mucosal injury was induced by 1-methyl-3-nitroso-1-nitrosoguanidine (MNNG) and a 10% NaCl solution, followed by treatment with either Vitacoenzyme or SJP. Histopathological changes in gastric tissues were evaluated using hematoxylin-eosin staining. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay. Western blot (WB) analysis was performed to detect COX-2 expression. Immunohistochemistry was used to assess TFF1 and TFF2 expression. Serum metabolomics was conducted to identify differential metabolites and enriched pathways, while proteins related to the FOXO signaling pathway were further examined in vivo . WB analysis was used to detect SIRT1, FOXO1, and STAT3. CAT and SOD2 activities were measured using biochemical assays. Multiplex immunohistochemistry was used to examine SIRT1-FOXO1 co-localization and FOXO1 nuclear localization. For the in vitro experiments, normal human gastric epithelial cells were treated with MNNG to induce inflammatory injury, followed by SJP administration in the presence or absence of the SIRT1 inhibitor EX-527. Results SJP alleviated gastric mucosal injury, reduced serum IL-6 levels and COX-2 expression, and significantly increased TFF1 and TFF2 expression. Metabolomics analysis identified 13 differential metabolites. The targets of these metabolites were intersected with gastritis-related targets, yielding 522 overlapping targets that were significantly enriched in the FOXO signaling pathway. In vivo and in vitro experiments showed that SJP upregulated SIRT1 and FOXO1 expression, increased CAT and SOD2 activities, inhibited STAT3 expression, and promoted FOXO1 nuclear localization. EX-527 blocked the restorative effects of SJP on FOXO1 expression and antioxidant enzyme activities. Conclusion SJP ameliorates gastric mucosal injury and inflammation, potentially through modulation of the SIRT1/FOXO1 axis.
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DOI
PubMed
高影响因子
npj Science of Food
·
2026
·
IF 9.7
Wang Xiaoran,Song Yagang,Zhao Wenyu,Liu Yuting,Fu Yiping,Zhang Yu,Zhao Quanyou,Miao Mingsan,Zhao Wenxia,Wang Xianbo,Li Zhanzhan
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health burden with limited therapeutic options. Cinnamomum cassia , a medicinal-food homologous plant, contains principal bioactive cinnamaldehyde (CA), whose anti-MASLD mechanisms require clarification. This study employed both a high-fat diet (HFD)-induced MASLD model and a free fatty acid (FFA)-stimulated cell model. CA administration attenuated intracellular lipid accumulation in vitro and ameliorated both hepatic steatosis and systemic hyperlipidemia in vivo, while inhibiting hepatic lipid peroxidation. Mechanistically, integrated RNA-seq, network pharmacology, siRNA, immunofluorescence, and transmission electron microscopy analyses identified the SIRT1/FOXO1–autophagy axis as CA’s key regulatory pathway. Gut microbiome profiling revealed CA’s capacity to ameliorate HFD-induced dysbiosis, particularly enriching Lachnospiraceae_NK4A136 . Fecal microbiota transplantation (FMT) and Spearman correlations link serum lipids and hepatic injury factors to gut microbiota, indicating partially microbiota-mediated metabolic modulation by CA. Collectively, CA ameliorates MASLD through coordinated autophagy enhancement and microbial homeostasis restoration, holding promise as a functional food ingredient for metabolic liver disease prevention.
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2024
·Vol. 38
·期 11
·e23681
·
IF 4.4
Shi-shi Liao,Le-le Zhang,Yi-guo Zhang,Jie Luo,Tulanisa Kadier,Ke Ding,Rong Chen,Qing-tao Meng
Ischemia–reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia–reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 μg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.
研究领域:
药理学
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病理生理学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ANIMAL SCIENCE
·
2026
·
IF 3.7
Zheng Jikang,Zhao Junyin,Li Minhao,Cheng Yuqin,Fang Xingqiang,Zhao Le,Zhao Yongju
Goat semen cryopreservation generates excessive reactive oxygen species (ROS), which impair post-thaw quality and physiological function. This study investigated the effects of resveratrol (RES) on cryopreserved goat sperm and the underlying signaling pathway. The results showed that supplementation with 150 μM RES significantly improved post-thaw sperm motility, plasma membrane integrity, and acrosome integrity (P < 0.05), enhanced SOD, CAT, and T-AOC activities, and reduced MDA content and sperm deformity rates (P < 0.05), while higher concentration (200 μM) showed no significant improvement compared to control, suggesting a detrimental effect of excessive RES. Furthermore, RES effectively alleviated cryo-induced ultrastructural damage to sperm. Mechanistically, RES activated AMPK signaling, increased AMPK phosphorylation, and upregulated the expression of SIRT1 and FoxO1 proteins. In contrast, the AMPK inhibitor Compound C partially blocked these beneficial effects. These findings indicate that RES improves the quality and antioxidant capacity of cryopreserved goat sperm by activating the AMPK/SIRT1/FoxO1 pathway, suggesting that RES can serve as a promising antioxidant additive for goat semen cryopreservation.
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产品关联
DOI
PubMed
高影响因子
Open Medicine
·
2023
·Vol. 18
·期 1
·
IF 2.1
Qi Duan,Junxia Wu
Dihydroartemisinin (DHA) has been found to inhibit the expression of von Willebrand factor (VWF), a marker of endothelial cell injury, but its mechanism in cerebral ischemia/reperfusion (I/R) injury remains obscure. In this study, I/R model was constructed through middle cerebral artery occlusion (MCAO) in rats, followed by DHA administration. The effect of DHA on rat cerebral I/R injury was investigated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin staining, TUNEL staining, and Western blot. Brain microvascular endothelial cells (BMVECs) isolated from newborn rats were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R), and then treated with DHA. The results showed that MCAO treatment induced infarction, nerve cell apoptosis, and brain tissue impairment in rats, which was mitigated by DHA. OGD/R inhibited viability and accelerated apoptosis of BMVECs, which was alleviated by DHA. I/R procedures or OGD/R up-regulated expressions of VWF, ATG7, Beclin1, and LC3-II/LC3-I ratio, while down-regulating Occludin, Claudin-5, ZO-1, P62, SIRT1, and FOXO1 expressions in vivo and in vitro ; however, these effects of I/R procedures or OGD/R were offset by DHA. VWF overexpression reversed the above effects of DHA on OGD/R-induced BMVECs. In summary, DHA ameliorates cerebral I/R injury in rats by reducing VWF level and activating autophagy-mediated SIRT1/FOXO1 signaling pathway.
研究领域:
神经科学
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药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Meng Chen,Yonglu Li,Xin Yu,Yaxuan Wang,Wen Chen,Xiang Ye,Yangyang Liu,Yong Jiang,Xiaodong Zheng
Tetrastigma hemsleyanum Diels et Gilg, a rare herbal plant native to China, possesses high medicinal value. More researches have focused on the flavones in the tubers of Tetrastigma hemsleyanum whereas polysaccharides attract few attentions. In this study, a purified polysaccharide (TTP-1) with the average molecular weights of 478.33 kDa was extracted from Tetrastigma hemsleyanum and conducted multiple analysis to identify its structural information. In vitro , TTP-1 could suppress the inflammation, cytotoxicity, genotoxicity, mitochondrial dysfunction and oxidative damage induced by LPS in RAW264.7 cells. Meanwhile, TTP-1 could attenuate inflammation via COX-2, iNOS, MAPKs pathways and ameliorate oxidative damage through Nrf2-Keap1, Sirt1-FoxO1 pathways in RAW264.7 cells. In vivo , the inflammation induced by LPS triggered the suppression of survival ratio and growing development, as well as the restrain of athletic ability in Caenorhabditis elegans . The treatment of TTP-1 reversed the situation induced by LPS. In a word, TTP-1 could ameliorate LPS-induced inflammation both in vitro and in vivo .
研究领域:
药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2025
·Vol. 63
·期 1
·1-14
·
IF 4.3
Cai Minghui,Guo Qi,Li Jiaxin,Dai Xiaoqi,Su Huiyu,Zhang Wenwen,Qiang Na,Li Geng,Jin Zihan,Zhu Hui
The factors influencing hippocampal aging are complex, and it remains challenging to identify effective anti-aging drugs and reveal pharmacological mechanisms. This study investigates the effects of autophagy mediated by the SIRT1/FoxO1 signaling pathway on resveratrol resistance to H 2 O 2 -induced aging and apoptosis in mouse hippocampal neurons. HT22 cells were treated with resveratrol and H 2 O 2 to evaluate the effects of resveratrol on H 2 O 2 -induced aging and apoptosis. The levels of P21, P53, BAX, Cleaved Caspase-3, and Bcl-2 were measured to estimate aging and apoptosis. Western blot, immunofluorescence assays, and transmission electron microscopy observation were used to detect the regulation of resveratrol on autophagy. 3-Methyladenine was used to block autophagy, and EX-527 was used to inhibit SIRT1. The changes of autophagy factors and the levels of SIRT1/FoxO1 signaling pathway were assayed. H 2 O 2 treatment induced aging in HT22 cells, manifesting increased levels of P21 and P53 and decreased cell viability. H 2 O 2 treatment aggravated apoptosis, showing increased levels of BAX and Cleaved Caspase-3, decreased levels of Bcl-2, and increased apoptotic cells. Resveratrol alleviated aging and apoptosis in H 2 O 2 -induced HT22 cells. Mechanically, resveratrol activated autophagy by up-regulating the levels of LC3B Ⅱ/Ⅰ and Beclin1 and down-regulating P62 against aging and apoptosis, which was abolished by 3-Methyladenine. Western blot results showed resveratrol activated SIRT1/FoxO1 signaling pathway which was related to regulation of autophagy. EX-527 treatment suggested resveratrol could not activate autophagy when the SIRT1/FoxO1 signaling pathway was blocked. These findings indicated that resveratrol activated autophagy via SIRT1/FoxO1 signaling pathway to protect against H 2 O 2 -induced aging and apoptosis in HT22 cells.
研究领域:
神经科学
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分子生物学
·
细胞生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Qing Liu,Zengying Sui,Shiyi Li,Miaomiao Wan,Meilan Xue,Xia Qiu,Hui Liang,Lirui Sun
Fucoidan is a sulfated polysaccharide derived from brown algae ( Saccharina japonica ), and exhibits immunomodulatory properties. Emerging evidence suggests a strong correlation between the development of food allergy and intestinal dysfunction. The present study aimed to investigate the potential anti-food allergy activity of fucoidan and to elucidate its mechanism at the intestinal barrier function. The ovalbumin (OVA)-induced allergy mouse model was established, exhibiting increased OVA-specific IgE, histamine, Th2 inflammatory response, and intestinal damage. Oral administration of fucoidan markedly alleviated allergic symptoms by inhibiting mast cell activation and modulating intestinal immune responses. Furthermore, fucoidan significantly ameliorated intestinal immunological dysregulation, maintained barrier integrity, modulated gut microbiota composition, and enhanced short-chain fatty acid (SCFA) production. Mechanistically, the protective effects of fucoidan were closely associated with activation of the AMPK/SIRT1/FOXO1 pathway, which correlated with improved intestinal barrier function. Collectively, these results demonstrate that fucoidan may protect against food allergy by enhancing intestinal barrier function, highlighting the potential of natural biological substances in addressing food allergy.
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DOI
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Wen Chen,Qiang Chu,Xiang Ye,Yuhao Sun,Yangyang Liu,Ruoyi Jia,Yonglu Li,Pengcheng Tu,Qiong Tang,Ting Yu,Chuan Chen,Xiaodong Zheng
Increasing attention has been brought to microplastics pollution recently, while emerging evidences indicate that nano-plastics degraded from microplastics are more of research significance owing to stronger toxicity. However, there is little study focused on the prevention of nano-plastics induced toxicity until now. Canidin-3-glucoside (C3G), a natural anthocyanin proved to possess multiple functions like antioxidant and intestinal tissue protection. Thus, we proposed whether C3G could act as a molecular weapon against nano-plastics induced toxicity. In Caco2 cell and Caenorhabditis elegans ( C. elegans ) models, we found that polystyrene (PS) nano-plastics exposure resulted in physiological toxicity and oxidative damage, which could be restored by C3G. More significantly in Caco2 cells, we observed that autophagy was activated via Sirt1-Foxo1 signaling pathway to attenuate PS induced toxicity after C3G intervention and further verified by adding autophagy inhibitor 3-Methyladenine (3-MA). Meanwhile, PS co-localization with lysosomes was observed, indicating the encapsulation and degradation of PS. In C. elegans , by detecting LGG-1/LC3 expression in GFP-targeted LGG-1 report gene (LGG-1:GFP) labeled transgenic DA2123 strain, the co-localization of LGG-1:GFP with PS was found as well, means that autophagy is involved in C3G’s beneficial effects. Furthermore, we were surprised to find that C3G could promote the discharge of PS from N2 nematodes, which reduces PS toxicity more directly.
研究领域:
环境科学
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毒理学
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细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Shuang Zhang,Lushuang Yu,Yonglu Li,Yangyang Liu,Xiang Ye,Xiaodong Zheng
The tubers of Apios americana Medikus possess high nutritional value and have been used as food in many countries for a long time. However, few researches have focused on the tuber polysaccharides. In the present study, a purified polysaccharide (ATP-1) was isolated with the average molecular weights of 12.16 kDa. ATP-1 significantly suppressed the release of nitric oxide (NO) and inflammatory cytokines from LPS-induced RAW 264.7 cells, as well as oxidative stress and mitochondrial dysfunction. Meanwhile, ATP-1 reduced oxidative damage via the NF-κB, MAPKs and Nrf2-Keap1 signaling pathways in RAW264.7 macrophages. Furthermore, autophagy was activated by HMGB1-Beclin1, Sirt1-FoxO1 and Akt-mTOR signaling pathways, leading to a relief of oxidative stress, mitochondrial dysfunction, inflammation and an expression enhancement of autophagy-related proteins, such as LC3, Beclin1, Atg4, Atg5, and Atg7. In summary, our results suggested that ATP-1 might help to activate the anti-inflammation system，resulting in prevention of LPS-induced damage in RAW264.7 cells.
研究领域:
药理学
·
免疫学
·
细胞生物学
·
生物化学
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DOI
PubMed
高影响因子
Food Bioscience
·
2021
·
IF 4.24
Qiang Chu,Ruoyi Jia,Chaowei Chen,Yaxuan Wang,Xin Yu,Yiru Zhang,Tao Wu,Xiaodong Zheng
Apios americana Medik leaves are rich in polyphenols and prevent glucose-induced damage in organisms. Polyphenols are a group of natural antioxidants. Therefore, a H 2 O 2 induced oxidative stress model of HepG2 cells was used to explore the protective effects of the Apios americana Medik leaves water extract (ALWE) against oxidative stress. Nine compounds were identified in ALWE using HPLC-TOF-MS including C 18 H 24 O 13 , which had not previously been reported. Fluorescence staining assays showed that the ALWE significantly decreased apoptosis, intracellular ROS generation, mitochondrial membrane potential (MMP) dissipation and mitochondrial membrane lipid peroxidation after ALWE pretreatment. Data from western blots showed that Keap1-Nrf2 and Sirt1-FoxO1 signaling pathways were involved in preventing H 2 O 2 induced oxidative stress. Transmission electron microscope and Western blot analyses indicated that autophagy contributed to the regulation of the oxidative balance. These results together indicated that ALWE is a potential antioxidant and autophagy activator, and it protects HepG2 cells against H 2 O 2 damage through activation of autophagy.
研究领域:
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）