Molecular Medicine Reports
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2021
·Vol. 24
·期 4
·1-8
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IF 2.952
Hongwei Shi,Qingfu Zeng,Yunjie Wei,Hong Yang,Heng Tang,Dan Wang,Peng Pu,Rui Feng
Pirarubicin (THP), one of the anthracycline anticancer drugs, is widely used in the treatment of various types of cancer, but its cardiotoxicity cannot be ignored. Canagliflozin, the first sodium‑glucose co‑transporter‑2 inhibitor approved by the USA FDA, has been shown to have a significant effect on cardiovascular damage caused by diabetes. However, it has not been reported whether it can resist THP‑induced cardiotoxicity. The aim of the present study was to investigate the effect of canagliflozin on THP‑induced cardiotoxicity and its mechanism. A rat model of cardiotoxicity induced by THP was established and canagliflozin treatment was performed at the same time. The changes of electrocardiography, cardiac coefficient and echocardiogram were observed. The levels of lactate dehydrogenase, brain natriuretic peptide, creatine kinase MB, cardiac troponin T, superoxide dismutase (SOD) and malondialdehyde were detected. The expression of SOD2, NADPH oxidase 2, pro/cleaved‑caspase‑ and Bcl‑2/Bax were evaluated by western blotting. The primary culture of cardiomyocytes was prepared to explore the effect in vitro. After eight weeks, a series of cardiotoxicity manifestations were observed in THP rats. However, canagliflozin treatment had no significant effect on the above adverse reactions. Similarly, further studies showed that canagliflozin had no significant effect on THP‑induced cardiomyocyte injury in vitro. The present study showed that there was no significant protective effect of canagliflozin on THP‑induced cardiotoxicity and cardiomyocyte injury.
研究领域:
药理学
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心脏病学
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肿瘤学
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DOI
PubMed
高影响因子
INFLAMMATION
·
2022
·Vol. 45
·期 3
·1362-1373
·
IF 4.657
Ji Xiang-Fen,Fan Yu-Chen,Sun Fei,Wang Jing-Wei,Wang Kai
Acute liver failure (ALF) is a deadly clinical disorder with few effective treatments and unclear pathogenesis. In our previous study, we demonstrated that aberrant Wnt5a expression was involved in acute-on-chronic liver failure. However, the role of Wnt5a in ALF is unknown. We investigated the expression of Wnt5a and its downstream c-Jun N-terminal kinase (JNK) signaling in a mouse model of ALF established by coinjection of D-galactosamine (D-Gal) and lipopolysaccharide (LPS) in C57BL/6 mice. We also investigated the role of Box5, a Wnt5a antagonist, in vivo. Moreover, the effect of Wnt5a/JNK signaling on downstream inflammatory cytokine expression, phagocytosis, and migration in THP-1 macrophages was studied in vitro. Aberrant Wnt5a expression and JNK activation were detected in D-Gal/LPS-induced ALF mice. Box5 pretreatment reversed JNK activation and eventually decreased the mortality rate of D-Gal/LPS-treated mice, with reduced hepatic necrosis and apoptosis, serum ALT and AST levels, and liver inflammatory cytokine expression, although the latter was not significant. We further demonstrated that recombinant Wnt5a (rWnt5a)-induced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA expression and increased THP-1 macrophage phagocytosis in a JNK-dependent manner, which could be restored by Box5. In addition, rWnt5a-induced migration of THP-1 macrophages was also reversed by Box5. Our findings suggested that Wnt5a/JNK signaling plays an important role in the development of ALF and that Box5 could have particular hepatoprotective effects in ALF.
研究领域:
肝病学
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免疫学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Ziwei Gao,Jinyang Ren,Chang Ke,Deyu Yang,Kexing Wang,Qi Wang,Xinyan Chen,Cong Chang,Zhenpeng Qiu,Chao Cai,Zhongshi Zhou,Yan Meng
An inulin-type fructan (CPS0.2B) from an edible traditional Chinese medicine (TCM) named Codonopsis pilosula was found to exhibit immunological enhancement both in vitro and in vivo. However, the commercial inulin, which has an almost identical molecular weight and monosaccharide composition as CPS0.2B, exhibited almost no biological activity in vitro. We found that this difference was attributed to the smaller particle size of CPS0.2B, facilitating enhanced cellular uptake through endocytosis. Further investigation into the corresponding immune-enhancing effect using THP-1 macrophage cells indicated that CPS0.2B can effectively activate the MAPK and NF-κB signaling pathways by stimulating the p65 protein both inside and outside the cell membrane. Additionally, in vivo strudy further confirmed CPS0.2B had an immune-enhancing effect on CTX-induced immune suppression model in mice. This study confirmed the immune-enhancing activity and related mechanisms of the inulin-type fructan CPS0.2B and, more importantly, demonstrated the significant role of the advanced structure of the polysaccharides in immunomodulatory effects.
研究领域:
免疫学
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生物化学
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药理学
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分子生物学
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中医药学
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碳水化合物化学
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2024
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IF 4.5
Yi Chen,Shasha Song,Yongfang Wang,Lili Wu,Jianbing Wu,Zhengmeng Jiang,Xinyu Li
Psoriasis (PSO) is a common inflammatory skin disease caused by multiple factors. Magnolia officinalis is an important medicinal plant in China, with various values such as ecology, medicine, food, and daily chemicals. However, its diverse application potential has not been fully explored. Magnolol (MGO) is the main active compound of Magnolia officinalis with significant anti-inflammatory effect. To investigate the application potential of MGO in inflammatory skin disease, the effects and underlying mechanisms of topical MGO treating psoriasis were explored in this study. Network pharmacology and molecular docking firstly predicted that topical MGO may treat psoriasis by regulating pyroptosis pathway and acting on caspase-1 (CASP1). In vitro experiments then demonstrated that MGO could inhibit the level of inflammatory cytokines and the key protein expression of NOD-like receptor protein 3 (NLRP3)/Caspase-1 pathway in lipopolysaccharide (LPS)-stimulated phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells. Meanwhile, MGO could inhibit CuSO 4 -induced neutrophils migration in Tg (mpx:EGFP) zebrafish by suppressing inflammation and pyroptosis. This study further indicated that topical application of MGO ameliorated imiquimod (IMQ)-induced psoriasis-like dermatitis by reducing the release of inflammatory factors and decreasing the key protein expression of pyroptosis-related NLRP3/Caspase-1 pathway. Metabolomics analysis revealed that topical application of MGO could significantly regulate tryptophan metabolism and affect the level of tryptophan in skin lesions. Tryptophan could also regulate inflammation-related genes and inhibit pyroptosis-related NLRP3/Caspase-1 pathway in LPS-stimulated PMA-differentiated THP-1 cells. In conclusion, this study suggested that topical MGO may ameliorate psoriasis-like dermatitis by inhibiting NLRP3/Caspase-1 pathway and regulating tryptophan metabolism.
研究领域:
药理学
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皮肤科
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分子生物学
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代谢组学
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DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2023
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IF 4.5
Yunbo Yan,Linqian Yu,Binyang Chen,Chang’an Cao,Hairong Zhao,Qiang Wang,De Xie,Yuemei Xi,Chenggui Zhang,Jidong Cheng
Background Gouty arthritis is characterized by the accumulation of monosodium urate crystals (MSU) in the synovial joints and surrounding tissues. Mastoparan M (Mast-M) is a biologically active peptide composed of 14 amino acids, extracted from wasp venom. This study aims to assess the impact of Mast-M on in vitro and in vivo gouty arthritis induced by lipolyaccharide (LPS) plus MSU crystal stimulation.Methods PMA-differentiated THP-1 macrophages were pre-treated with Mast-M or left untreated, followed by stimulation with LPS and MSU crystals. Cell lysates were collected to assess the expression of the NLRP3 inflammasome, inflammatory signaling pathways, and oxidative stress. Furthermore, to evaluate the in vivo anti-inflammatory effect of Mast-M, an experimental acute gouty arthritis mouse model was established through intra-articular injection of MSU crystals.Results Mast-M treatment demonstrated significant inhibition of the phosphorylation of MAPKs/NF-κB signaling pathways and reduction in oxidative stress expression in LPS and MSU-induced THP-1 macrophages. This resulted in the suppression of downstream NLRP3 inflammasome activation and IL-1β release. In vivo, Mast-M effectively attenuated the inflammation induced by MSU in mice with gouty arthritis. Specifically, Mast-M reduced swelling in the paws, inhibited the infiltration of neutrophils and macrophages into periarticular tissue, and decreased the activation of the NLRP3 inflammasome and IL-1β production.Conclusion Mast-M significantly improves gouty arthritis, and its potential mechanism may be achieved by inhibiting the MAPK/NF-κB pathway and alleviating oxidative stress, thus suppressing the activation of NLRP3 inflammasomes.
研究领域:
免疫学
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风湿病学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Biochemistry and Biophysics Reports
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2024
·
IF 2.3
Youyang Liu,Yunlu Zhao,Qi Guo,Pengfei Wang,Peixuan Li,Qingqing Du,Huazhou Xu,Qingyin Yu,Xiaoyi Zhao,Weiya Zhang,Shengjun An,Shuhui Wu
Immune responses, especially NLRP3 signaling in macrophages, play critical roles in rheumatoid arthritis (RA), an autoimmune and inflammatory disease. In this study, we aimed to identify novel therapies for RA. We focused on sophoricoside (SOP), an isoflavone glycoside isolated from Sophora japonica . We predicted the targets of SOP and performed a Gene Ontology analysis to assess its effects. The results suggested that SOP is related to inflammation regulation. We verified these findings by performing in vitro experiments with M1 macrophages differentiated from human peripheral blood monocytes (THP-1 cells). Sophoricoside administration reduced inflammatory activity and NLRP3, Caspase-1, and IL-1β protein levels in macrophages. In addition, SOP and triptolide (TP) was administered intragastrically to male SD rats (n = 40) in a collagen-induced arthritis model. We observed that SOP and TP reduced the inflammatory responses and symptoms of RA. Moreover, unlike TP, SOP showed no liver or kidney toxicity in rats. In conclusion, SOP reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling and has potential for future clinical applications as an ideal therapy for RA.
研究领域:
免疫学
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药理学
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风湿病学
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炎症
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-16
·
IF 10.6
Zhang Li,Li Yujiao,Liu Xing,He Xiaolu,Zhang Jieyu,Zhou Jun,Qiao Youbei,Wu Hong,Sun Fangfang,Zhou Qing
Macrophages are multifunctional innate immune cells that play indispensable roles in homeostasis, tissue repair, and immune regulation. However, dysregulated activation of macrophages is implicated in the pathogenesis of various human disorders, making them a potential target for treatment. Through the expression of pattern recognition and scavenger receptors, macrophages exhibit selective uptake of pathogens and apoptotic cells. Consequently, the utilization of drug carriers that mimic pathogenic or apoptotic signals shows potential for targeted delivery to macrophages. In this study, a series of mannosylated or/and phosphatidylserine (PS) -presenting liposomes were developed to target macrophages via the design of experiment (DoE) strategy and the trial-and-error (TaE) approach. The optimal molar ratio for the liposome formulation was DOPC: DSPS: Chol: PEG-PE = 20:60:20:2 based on the results of cellular uptake and cytotoxicity evaluation on RAW 264.7 and THP-1 in vitro. Results from in vivo distribution showed that, in the DSS-induced colitis model and collagen II-induced rheumatoid arthritis model, PS-presenting liposomes (PS-Lipo) showed the highest accumulation in intestine and paws respectively, which holds promising potential for macrophage target therapy since macrophages are abundant at inflammatory sites and contribute to the progression of corresponding diseases. Organs such as the heart, liver, spleen, lung, and kidney did not exhibit histological alterations such as inflammation or necrosis when exposed to PC-presenting liposomes (PC-Lipo) or PS-Lipo. In addition, liposomes demonstrated hemobiocompatibility and no toxicity to liver or kidney for circulation and did not induce metabolic injury in the animals. Thus, the well-designed PS-Lipo demonstrated the most potential for macrophage target therapy.
研究领域:
药理学
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免疫学
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药物递送系统
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炎症
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产品关联
DOI
PubMed
高影响因子
Theranostics
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2020
·
IF 8.579
Xinglu Jiang,Xiaobo Fan,Rui Zhang,Wei Xu,Hailu Wu,Fengfeng Zhao,Han Xiao,Chen Zhang,Chenggui Zhao,Guoqiu Wu
Rationale: Drug combination therapy for cancer treatment exerts a more potent antitumor effect. The targeted delivery and release of multiple drugs in a patient's body thus presents a more effective treatment approach, warranting further research. Methods: Two antitumor drugs (ICG: indocyanine green and THP: pirarubicin) were successfully screened to sequentially trigger self-assembling peptides (P60) to produce bacteria-sized particles (500-1000 nm, P60-ICG-THP). First, after mixing equal amount of P60 and ICG, trace amount of water (the mass ratio between P60 and water: 100:1) was used to trigger their assembly into P60-ICG. Subsequently, the assembly of P60-ICG and THP was further triggered by ultrasound treatment to produce P60-ICG-THP. Results: P60-ICG-THP constituted a cluster of several nanoparticles (50-100 nm) and possessed a negative charge. Owing to its size and charge characteristics, P60-ICG-THP could remain outside the cell membrane, avoiding the phagocytic clearance of blood and normal tissue cells in vivo . However, after localizing in the tumor, the size and charge switches of P60-ICG-THP, rapidly triggered by the low pH of the tumor microenvironment, caused P60-ICG-THP to segregate into two parts: (i) positively charged nanoparticles with a size of approximately 50 nm, and (ii) negatively charged particles of an uneven size. The former, mainly carrying THP (chemotherapeutic agent), could immediately cross the cell membrane and deliver pirarubicin into the nucleus of tumor cells. The latter, carrying ICG (used for photothermal therapy), could also enter the cell via the endocytosis pathway or accumulate in tumor blood vessels to selectively block the supply of nutrients and oxygen (cancer starvation). Both these particles could avoid the rapid excretion of ICG in the liver and were conducive to accumulation in the tumor tissue for photothermal therapy. Conclusion: Our drug delivery system not only achieves the precise subcellular delivery of two anticancer drugs due to their size and charge switches in the tumor site, but also provides a new strategy to combine chemotherapy, photothermal therapy, and cancer starvation therapy for the development of a highly efficient antitumor therapeutic regimen.
研究领域:
肿瘤学
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药理学
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纳米技术
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生物医学工程
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癌症治疗
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2022
·
IF 5.223
Li-Hua Zhu,Ying-Yin Xu,Li-ping Zhu,Xian Zheng,Cui-Hua Jiang,Jian-Jing Liu,Jian Zhang,Zhi-Qi Yin
As a new and safe food resource, Cyclocarya paliurus (CP), rich in flavonoids, exhibits hypouricemic, anti-inflammatory and antioxidative properties. However, whether CP aqueous extract (CPA) still possesses the ameliorative effects on hyperuricemia (HUA) and urate-induced renal inflammation remains vacant. In HUA mice, CPA could significantly reduce serum uric acid (UA), alleviate kidney damage and liver steatosis, inhibit xanthine oxidase (XOD) activity, ameliorate renal urate transporters and renal inflammation by inhibiting NLRP3 inflammasome and interleukin-1β (IL-1β). Moreover, the flavonoids quercetin-3- O-β- D-galactopyranoside, quercetin-3- O-β- D-glucopyranoside, and quercetin-3- O-α -L-rhamnopyranoside from CPA could significantly reduce IL-1β and interleukin-6 (IL-6) in MSU-challenged THP-1 cells. Noticeably, quercetin-3- O-β- D-galactopyranoside could inhibit the intracellular XOD activity, reduce intracellular ROS and the expression of pro-IL-1β, IL-1β, and NLRP3 inflammasome. Collectively, CPA shows appreciable therapeutic effects on HUA and evoked renal inflammation. Quercetin-3- O-β -D-galactopyranoside, quercetin-3- O-β -D-glucopyranoside, and quercetin-3- O-α -L-rhamnopyranoside might be the major active compounds of CPA, which obtain the favorable effects through blocking the activation of ROS/NLRP3/IL-1β pathway.
研究领域:
药理学
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营养学
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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
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
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IF 5.4
Liting Zhu,Linjie Mu,Xiaoqiu Ni,Feng Wang,Xinyi Peng,Yujiu Gao,Tingting Wei,Congcong Zeng,Yongheng Bai,Fangyan Wang,Zhengzhong Yuan,Jinguo Cheng
Ethnopharmacological relevance Xin-Zi-Sheng-Wan Decoction (XZSWD), a formulation rooted in the classic Zi-Sheng Pill first recorded in the Qing-dynasty compendium “ Golden Mirror of Medicine ,” is traditionally employed to resolve turbid pathogenic stagnation and restore metabolic equilibrium. Modern ethnopharmacological studies reveal a marked uric acid–lowering effect, although its precise molecular mechanisms have yet to be fully clarified. Aim of the study This study aimed to evaluate the therapeutic efficacy of XZSWD in hyperuricemia (HUA)-induced kidney injury and to elucidate its molecular mechanisms. Methods UPLC-QTOF/MS was used to identify compounds in XZSWD medicated serum. A HUA mouse model was induced by potassium oxonate and hypoxanthine to evaluate the therapeutic effects of XZSWD on renal injury. RNA-Seq, qRT-PCR, Western blot, immunofluorescence, and flow cytometry were applied to investigate immune infiltration and key signaling pathways. A THP-1/HK-2 co-culture system combined with SPP1 overexpression and knockdown was used to explore the molecular mechanisms. Results 99 compounds were identified in XZSWDS. XZSWD improved renal function, reduced serum uric acid levels, and downregulated macrophage-related inflammatory genes while modulating mixed M1/M2 polarization. XZSWD also inhibited the SPP1-CD44 axis and downstream SRC/FAK/β-Catenin signaling to reduce renal extracellular matrix (ECM) deposition. In vitro, SPP1 was identified as a critical target mediating these effects. Conclusions XZSWD alleviates HUA-induced renal injury by suppressing macrophage-mediated inflammation via regulation of the SPP1–CD44 axis and SRC/FAK/β-Catenin signaling, highlighting its therapeutic potential for HUA-related renal dysfunction.
研究领域:
民族药理学
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肾脏病学
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免疫学
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信号转导
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植物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2024
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IF 4.2
Chunmeng Ding,Zhenguo Shen,Ruonan Xu,Yajing Liu,Mengyue Xu,Chenyu Fan,Dongyue Hu,Tian Xing
Aim To investigate the impact of exosomes released by Porphyromonas gingivalis -Lipopolysaccharide activated THP-1 macrophages and human periodontal ligament fibroblasts on hepatocyte fat metabolism. Results The liver of rats with experimental periodontitis showed obvious steatosis and inflammation compared with control rats. The culture supernatant of macrophages and human periodontal ligament fibroblasts (hPDLFs), when stimulated with Pg-LPS, induced lipogenesis in HepG2 cells. Furthermore, the lipid-promoting effect was effectively inhibited by the addition of the exosome inhibitor GW4869. Subsequently, we isolated exosomes from cells associated with periodontitis. Exosomes released by Pg-LPS-stimulated macrophages and hPDLFs are taken up by hepatocytes, causing mRNA expression related to fat synthesis, promoting triglyceride synthesis, and aggravating NAFLD progression. Finally, two sets of exosomes were injected into mice through the tail vein. In vivo experiments have also demonstrated that periodontitis-associated exosomes promote the development of hepatic injury and steatosis, upregulate SCD-1 expression and inhibit the AMPK signaling pathway. Conclusions In conclusion, we found that exosomes associated with periodontitis promote hepatocyte adipogenesis by increasing the expression of SCD-1 and suppressing the AMPK pathway, which indicates that close monitoring of the progression of stomatopathy associated extra-oral disorders is important and establishes a theoretical foundation for the prevention and management of fatty liver disease linked to periodontitis.
研究领域:
分子生物学
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细胞生物学
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病理学
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药理学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
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IF 10.7
Pei Lin,Qiqi Wang,Qi Wang,Jiayun Chen,Liangliang He,Zifei Qin,Shaoping Li,Jingyan Han,Xinsheng Yao,Yang Yu,Zhihong Yao
Allium Macrostemon Bge. (AMB) is a well-known homology of herbal medicine and food that has been extensively used for thousands of years to alleviate cardiovascular diseases. It contains a significant amount of polysaccharides, yet limited research exists on whether these polysaccharides are responsible for its cardiovascular protective effects. In this study, the anti-atherosclerosis effect of the crude polysaccharides of AMB (AMBP) was evaluated using ApoE −/− mice fed a high-fat diet, along with ox-LDL-induced Thp-1 foam cells. Subsequently, guided by the inhibitory activity of foam cells formation, a major homogeneous polysaccharide named AMBP80-1a was isolated and purified, yielding 11.1 % from AMB. The molecular weight of AMBP80-1a was determined to be 10.01 kDa. AMBP80-1a was firstly characterized as an agavin-type fructan with main chains consisting of →1)- β - d -Fru f -(2→ and →1,6)- β - d -Fru f -(2→ linked to an internal glucose moiety, with →6)- β - d -Fru f -(2→ and β - d -Fru f -(2→ serving as side chains. Furthermore, the bio-activity results indicated that AMBP80-1a reduced lipid accumulation and cholesterol contents in ox-LDL-induced Thp-1 foam cell. These findings supported the role of AMBP in alleviating atherosclerosis in vivo/vitro . AMBP80-1a, as the predominant homogeneous polysaccharide in AMB, was expected to be developed as a functional agent to prevent atherosclerosis.
研究领域:
药理学
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心血管疾病
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分子生物学
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营养保健品
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）