CURRENT ISSUES IN MOLECULAR BIOLOGY
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2025
·Vol. 47
·期 12
·991
·
IF 3
Lisha Li,Zhen Yu,Xuehua Lu,Pei Yang,Shuxia Zhang,Qinghua Lin,Junyong Han
Background: Adhesion G protein-coupled receptor G6 ( ADGRG6 ), also known as GPR126 , has been implicated in several malignancies. However, its expression pattern, clinical significance, and mechanistic role in pancreatic adenocarcinoma (PAAD) remain unclear. Methods: We combined multi-omics analyses, tissue microarray immunohistochemistry, and a series of functional experiments, including 2D and 3D spheroid cultures, zebrafish xenografts, and murine tumor models—to investigate the expression, clinical significance, and mechanism of ADGRG6 in PAAD. The association between ADGRG6 expression and immune infiltration was assessed using TIMER and GEPIA databases, followed by mechanistic validation through ADGRG6 modulation in PAAD cell lines. Results: ADGRG6 was significantly overexpressed in PAAD and correlated with larger tumor size, higher grade, advanced TNM stage, and poor overall survival. Multivariate logistic regression confirmed that high ADGRG6 expression was independently associated with higher pathological grade. Functionally, ADGRG6 silencing markedly inhibited PAAD cell proliferation, migration, and invasion in both 2D and 3D cultures, as well as in zebrafish and nude mouse xenograft models. Integrated transcriptomic and immune analyses revealed that ADGRG6 expression positively correlated with mast cells, macrophages (M1/M2), Th2/Th17 subsets, and interferon–responsive neutrophils. Mechanistically, ADGRG6 silencing reduced STAT6 phosphorylation and GATA3 expression, consistent with the suppression of the NF-κB→STAT6→GATA3 axis. Conclusions: ADGRG6 functions as an oncogenic driver in PAAD, promoting tumor progression and fostering an immunosuppressive microenvironment via NF-κB/STAT6 signaling. These findings not only broaden the mechanistic understanding of ADGRG6 function but also suggest it as a promising target for therapeutic intervention in PAAD.
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Food Science & Nutrition
·
2025
·Vol. 13
·期 12
·e71310
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IF 3.8
Fan Cao,Hua Wu,Zhen He,Mengxin Di,Bin Liu,Zhenwei Chen,Jieming Xie,Yonghong Zhang,Xinhua Ma
Melia azedarach L., also known as the chinaberry tree, has long been used in traditional medicine to treat inflammatory conditions. In this study, we preliminarily investigated the anti-inflammatory effect of 21 α -methylmelianol (MMN), a tirucallane-type triterpenoid isolated from M. azedarach , in lipopolysaccharide (LPS)-mediated RAW264.7 macrophages in vitro and in a dextran sodium sulfate (DSS)-stimulated ulcerative murine colitis model in vivo. MMN reduced LPS-stimulated nitric oxide production without inducing cytotoxicity. It significantly attenuated LPS-induced protein expression of reactive oxygen species and effectively suppressed the production of pro-inflammatory factors, including tumor necrosis factor-alpha (TNF- α ), interleukin (IL)-6, and IL-1 β . In addition, mechanistic investigations showed that MMN inhibited signal transduction and activator of STAT3 phosphorylation and activation of nuclear factor κ B (NF- κ B). In mice with DSS-induced colitis, MMN attenuated DSS-mediated pathological manifestations, including colon shortening, body weight loss, and histopathological alterations. Its in vivo effects were associated with the regulation of pro- and anti-inflammatory cytokine levels through suppression of the NF- κ B signaling cascade and downstream inflammatory pathways. Collectively, these findings provide compelling evidence of the anti-inflammatory properties of MMN and highlight its therapeutic potential for the management of inflammatory disorders.
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Food Bioscience
·
2025
·
IF 5.9
Jingwen Yu,Shilian Zheng,Abdul Mueed,Zeyuan Deng,Hongyan Li
The objectives of this study were to evaluate the antioxidant interactions and underlying mechanisms of the combinations of purple carrot anthocyanins extracts (PCAE) and red papaya carotenoids extracts (RPCE) using tert-butyl hydrogen peroxide (TBHP)-induced human umbilical vein endothelial cells (HUVEC). The results revealed that cyanidin-3-xylosyl (feruloyl glucosyl) galactoside (731.65±2.66 μg/mg) and lycopene (787.50±5.73 μg/mg) were the dominant anthocyanins and carotenoids in purple carrot and papaya, respectively. Cellular antioxidant assays, including cellular antioxidant activity (CAA) and antioxidant enzymes expression, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, showed that in the combinations which contained more hydrophilic PCAE, the combinations would tend to show synergistic effects. When RPCE were in the majority, the combinations would tend to show antagonistic effects. Reverse transcriptase-PCR and western blot analysis revealed the underlying mechanisms of synergistic/antagonistic antioxidant interactions were that they significantly inhibited intracellular ROS generation, exhibiting either synergistic/antagonistic effects on reducing mitochondrial ROS levels, restoring the mitochondrial membrane potential, and inhibiting the activity of the nicotinamide adenine dinucleotide phosphate oxidase 4. Meanwhile, they also reduced cellular ROS level via inhibition of the nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) signaling pathway, to elevate the activities of antioxidant enzymes based on HUVEC cell model. The synergistic/antagonistic antioxidant effects of phytochemical combinations supported their potential as functional food ingredients for cardiovascular diseases prevention.
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AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·Vol. 51
·期 08
·2157-2173
·
IF 5.7
Zhenfeng Liu,Wuming Zhou,Qingyang Liu,Zhirong Huan,Qiubo Wang,Xin Ge
Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos , has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15 mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1 β , IL-6, and tumor necrosis factor α (TNF- α ) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86 + ) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206 + ) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF- κ B pathway activation via inhibiting NF- κ B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF- κ B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.
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ACS Omega
·
2024
·
IF 3.7
Hao Xu,Ning Ning Guo,Chen Ying Zhu,Lin Yan Ye,Xing Yi Yan,Yong Qin Liu,Ze Yan Zhang,Guangji Zhang,Liaqat Hussain
Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Zhou-Wei Wu,Xing-Rong Peng,Xiao-Cui Liu,Luan Wen,Xin-Yu Tao,Abdulbaset Al-Romaima,Ming-Yi Wu,Ming-Hua Qiu
Lepidium meyenii Walp., also known as the “Peruvian national treasure”, is a popular functional food in the daily lives of Peruvian people due to its bioactive with main polysaccharides. However, studies on polysaccharides isolated from Lepidium meyenii were few. Two new highly heterogeneous polysaccharides, MCP-1a and MCP-2b, were isolated and purified from the tuber of Lepidium meyenii . The structure characterization revealed that MCP-1a primarily consisted of D-Glc and had a molecular weight of 6.6 kDa. Its backbone was composed of 1,4,6- α -D-Glc, while branches feature T- α -L-Ara, 1,5- α -L-Ara, and T- α -D-Glc attached to the O -6 positions. MCP-2b was a rare arabinogalactan with a molecular weight of 49.4 kDa. Interestingly, the backbone of MCP-2b was composed of 1,6- β -D-Gal, 1,3,6- β -D-Gal with a few 1,3- β -D-Glc p A-4-OMe units inserted. Side chains of MCP-2b were mainly composed of 1,3- β -D-Gal, T- β -D-Gal, T- α -L-Ara, 1,5- α -L-Ara, with trace amounts of 1,4- β -D-Glc and T- β -D-Glc. The bioactivity assay results revealed that MCP-1a and MCP-2b increased the release of NO, IL-1 β , TNF- α , and IL-6 from RAW 264.7 cells at concentrations ranging from 50 μg/mL to 400 μg/mL. Furthermore, MCP-1a and MCP-2b could promote the expression of key transcription factors (IκB- α , p-IκB- α , p65, and p-p65) in the NF-κB pathway, indicating that MCP-1a and MCP-2b had potential immunomodulatory activities.
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Catalysts
·
2025
·Vol. 15
·期 8
·725
·
IF 4
Bingxian Zhu,Yachao Liu,Yue Yan,Hui Wang,Yu Zhang,Ying Xin,Weijuan Xu,Qingshan Zhao
Hydrogen energy is a pivotal carrier for achieving carbon neutrality, requiring green and efficient production via water electrolysis. However, the anodic oxygen evolution reaction (OER) involves a sluggish four-electron transfer process, resulting in high overpotentials, while the prohibitive cost and complex preparation of precious metal catalysts impede large-scale commercialization. In this study, we develop a FeCo-based bimetallic deep eutectic solvent (FeCo-DES) as a multifunctional reaction medium for engineering a three-dimensional (3D) coral-like FeOOH-Co2(OH)3Cl/NF composite via a mild one-step impregnation approach (70 °C, ambient pressure). The FeCo-DES simultaneously serves as the solvent, metal source, and redox agent, driving the controlled in situ assembly of FeOOH-Co2(OH)3Cl hybrids on Ni(OH)2/NiOOH-coated nickel foam (NF). This hierarchical architecture induces synergistic enhancement through geometric structural effects combined with multi-component electronic interactions. Consequently, the FeOOH-Co2(OH)3Cl/NF catalyst achieves a remarkably low overpotential of 197 mV at 100 mA cm−2and a Tafel slope of 65.9 mV dec−1, along with 98% current retention over 24 h chronopotentiometry. This study pioneers a DES-mediated strategy for designing robust composite catalysts, establishing a scalable blueprint for high-performance and low-cost OER systems.
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Frontiers in Pharmacology
·
2018
·
IF 3.831
Yang Junfa,Liu Qingxue,Cao Shiyang,Xu Tao,Li Xiaofeng,Zhou Dandan,Pan Linxin,Li Changyao,Huang Cheng,Meng Xiaoming,Zhang Lei,Wang Xiao
During the liver fibrosis recovery stage tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can effectively induce apoptosis of activated hepatic stellate cells (HSCs). Normal hepatic stellate cells are resistant to TRAIL cytotoxicity. Therefore, enhancing the sensitivity of TRAIL-induced apoptosis of HSCs may be useful to treat hepatic fibrogenesis. Here, we demonstrated that miR-145 and TRAIL were down-regulated in both liver fibrosis tissue samples and transforming growth factor-β1 induced HSCs, concomitant with increased the expression of ZEB2. In addition, we found that mimics-mediated over-expression of miR-145 led to resistance to the ZEB2 expression and up-regulation of the TRAIL-induced apoptosis after treatment of LX-2 cells with TRAIL. Furthermore, ZEB2-siRNA transfected LX-2 cells showed the increased sensitivity to TRAIL-induced apoptosis. Whereas, opposite results were obtained in miR-145-inhibitor group or ZEB2 plasmid group. Moreover, miR-145 regulated ZEB2 gene expression by specifically interacting with the 3′-UTR of ZEB2 mRNA to inhibit the expression of ZEB2. Further studies showed that the over-expression of ZEB2 could inhibit TRAIL-induced apoptosis via inhibiting nuclear factor-κB (NF-κB) signaling pathway in LX-2 cells. Collectively, our data suggest that up-regulation of miR-145 can down-regulate ZEB2 expression, consequently promoting TRAIL-induced apoptosis in LX-2 cells through NF-κB signaling pathway, which facilitates the resolution of liver fibrosis.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2022
·Vol. 45
·期 12
·1733-1742
·
IF 2.264
Yongbin Jing,Mingkun Jia,Jinpeng Zhuang,Dong Han,Changlong Zhou,Jinglong Yan
Osteosarcoma (OS) is the most common primary malignant bone tumor and is mainly diagnosed in children. Toll-like receptor 9 (TLR9) is expressed in various tumor cells and was correlated with cancer progression. However, the underlying mechanism of TLR9 on the OS progression remains unclear. Our previous study demonstrated that the expression of TLR9 was positively correlated with the development stage of OS. Herein, we further evaluated the actual roles and the molecular mechanism of TLR9 on regulating OS cell proliferation and metastasis. Our data showed that TLR9 was upregulated in OS cells compared to normal osteoblastic cells, and knockdown of TLR9 inhibited OS cell proliferation and induced cell cycle arrest by the decreased expression of cyclin D1, CDK2, and p-Rb, while TLR9 overexpression exerted the inverse effects. Furthermore, TLR9 overexpression could enhance the migration and invasion activities of the OS cells by the upregulation of matrix metalloproteinases 2 (MMP2) and MMP9, and the opposite result was observed in TLR9-silenced cells. Moreover, the nuclear factor kappa B (NF-κB) signaling pathway was activated by TLR9, and TLR9-induced malignant phenotype of OS cells was abrogated by the NF-κB antagonist BAY11-7082. Our study indicated that TLR9 might play a critical role in facilitating OS progression by activating the NF-κB signaling pathway, which may provide a valuable therapeutic target for OS.
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BIOCHIMIE
·
2018
·
IF 3.188
Ji Li,Yanping Li,Shuang Pan,Lin Zhang,Lina He,Yumei Niu
Paeonol is a natural phenolic compound in Moutan Cortex with multiple biological functions, such as anti-inflammatory and anti-oxidant activity. Recent evidence has proven that persistent inflammation, oxidative stress , along with nuclear factor E2-related factor 2 (Nrf2) signaling dysfunction in periodontium are the possible causes of alveolar bone resorption , and ultimately lead to periodontitis. The present study was designed to explore the protective effects of paeonol on ligation-induced periodontitis in rats, and investigate the possible mechanism. We found that treatment with paeonol (40, 80 mg/kg, intraperitoneal injection) for 7 days remarkably decreased the expression of receptor activator of nuclear factor kappa-B ligand increased the expression of osteoprotegrin and inhibited the formation of osteoclasts . This function of paeonol might be correlated with its ability to reduce inflammatory factors (IL-1β, IL-6 and TNF-α) and alleviate oxidative stress (SOD, MDA, GSH and ROS) in gingival tissues. Besides, paeonol increased Nrf2 activity. Silence of Nrf2 using specific siRNA diminished the inhibitory effect of paeonol on NF-κB p65 activation and downstream expression, suggesting that Nrf2 was essential for protective effect of paeonol. These results showed that paeonol protected against periodontitis-aggravated osteoclastogenesis and alveolar bone lesion via regulating Nrf2/NF-κB/NFATc1 signaling pathway .
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KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
·
2025
·
IF 3.1
Meng-Si Li,Kai Liu
IgA nephropathy (IgAN), the most common form of glomerulonephritis, is a major and growing public health issue. It results from intestinal barrier dysfunction that leads to mesangial deposition of pathogenic galactose-deficient IgA1 (Gd-IgA1) and renal inflammation. This study aimed to investigate the therapeutic effects and associated mechanisms of forsythiaside A on intestinal barrier injury in IgAN in animal models. Rats were treated with bovine serum albumin (BSA), carbon tetrachloride (CCl 4 ), and lipopolysaccharide (LPS) to induce IgAN, followed by intragastric administration of forsythiaside A once daily from weeks 15 to 20 after model establishment. Biochemical markers, including 24-h urinary protein, blood urea nitrogen (BUN), serum creatinine (SCr), renal and intestinal tissue pathology, and levels of pro-inflammatory cytokines in the serum, kidney, and intestine, intestinal tight junction proteins, and TLR4/NF-κB pathway components were examined. The results showed that forsythiaside A decreased 24-h urinary protein, BUN, and SCr levels, alleviated renal damage, and attenuated glomerular and tubular lesions, collagen deposition, and glomerular IgA deposition in IgAN rats. Forsythiaside A treatment inhibited CD68-positive macrophage infiltration in renal tissues and downregulated serum and renal levels of IL-1β, IL-6, and TNF-α, while also alleviating intestinal barrier injury and intestinal inflammation, as shown by reduced levels of IL-1β, IL-6, and TNF-α and increased expression of the intestinal tight junction proteins occludin and ZO-1. Lastly, forsythiaside A treatment lowered serum LPS concentrations, as well as renal and intestinal levels of TLR4, p-NF-κB p65, and p-IκBα, and raised both renal and intestinal levels of IκBα. Collectively, forsythiaside A was found to ameliorate the progression of IgAN in rats by alleviating inflammation and intestinal barrier injury by suppression of TLR4/NF-κB signaling.
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ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Jiaqi Xu,Qiuhui Qian,Min Xia,Xuedong Wang,Huili Wang
Trichlorocarban (TCC) is ubiquitously detected in environmental matrices, while there is a paucity of information regarding its systemic toxicity. In the present study, we observed that TCC exposure led to high embryo mortality, delayed hatching and yolk absorption, as well as increased malformations, such as closure of swim sac and yolk sac edema. Meanwhile, TCC affected the formation and branch of subintestinal veins (SIVs), intersegmental vessels and posterior cardinal veins. Especially, the SIVs were shrunk, and their branches were reduced or even broken along with reduced coverage area. TCC-induced oxidative stress and excessive apoptosis resulted from abnormal expression of the anti/pro-apoptotic genes. Significant reduction in the number and aggregation function of immune cells proved that TCC had prominent immunotoxicity to zebrafish. TCC-targeted TLR4 signaling pathway was demonstrated by abnormal expression of the marker genes ( tlr4 , MyD88 and nf-κb ) and release of the downstream inflammatory factors (TNF-α, IL-6, etc.). Inhibition of TLR4/MyD88/NF-κB pathway by an inhibitor (CA-4948) rescued the decreasing trend of the immune cells induced by TCC. Molecular docking results demonstrated that TCC could stably bind to TLR4 receptor to form hydrogen bonds and hydrophobic interactions with amino acids. Overall, these findings reveal the underlying molecular mechanisms on TCC-induced developmental and immune toxicity to zebrafish.
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