Future Medicinal Chemistry
·
2022
·Vol. 14
·期 9
·
IF 4.767
Jiao Liu,Xiaoxuan Wang,Yuan Cheng,Yinghua Yu,Maofang Zhao,Jie Huang,Peiquan Yu,Qian Fu,Yilin Song,Yi Liu
Background: H2S is the third gas transmitter affecting the growth, reproduction and survival of cancer cells. However, the H2S anticancer and antitumor mechanism still needs to be further studied. Methods: Here, FHS-1 was synthesized utilizing excited-state intramolecular proton transfer to detect H2S in MCF-7 cells, and investigated the effects of varying concentrations NaHS on apoptosis. Results: The study found that FHS-1 detects H2S levels with high selectivity and pH stability and that H2S may regulate apoptosis in MCF-7 cells through the p53/mTOR/STAT3 pathway. Conclusion: Researching the influence of H2S on apoptosis can serve as a theoretical foundation for future research into H2S-related anticancer medicines, and the H2S probe can be used as an effective cancer screening tool.Graphical abstract
研究领域:
癌症生物学
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细胞信号传导
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药物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Genetics and Genomics
·
2025
·
IF 7.1
Wuming Qin,Xiaobo Yang,Lu Zhang,Linghui Cao,Shi Ouyang,Dafeng Yang,Yangzhao Zhou,Anji Chen,Tao Liao,Xinyu Zhu,Yuting Liu,Wei Tang,Tongtong Ma,Yiyue Tang,Yonghe Ding,Yun Deng
LIM zinc finger domain containing 1 (LIMS1), an evolutionally conserved LIM domain adaptor protein, is implicated in diverse pathologies, including cancer and neurological disorders. However, its roles in cardiac diseases and the underlying mechanisms remain unclear. Here, we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure. We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy (DCM) and murine cardiomyocytes, suggesting that LIMS1 dysregulation contributes to cardiac pathology. Using CRISPR/Cas9 technology, we generate a zebrafish model of lims1 loss-of-function mutant, which exhibits severe cardiac chamber remodeling, systolic dysfunction, and premature mortality, demonstrating the essential role of lims1 in maintaining cardiac integrity. Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1 -deficient hearts. Strikingly, pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes. Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation, offering insights into cardiac remodeling and potential therapeutic strategies.
研究领域:
心血管病学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Nanyu Cao,Heyang Wang
Regular insulin therapy is significantly related to worse cardiovascular outcomes in patients with type 2 diabetes and heart failure. However, the mechanisms of the causal relationship remain unclear. In this study, we observed the effect of insulin on cardiac structure and function and found that insulin dramatically augmented angiotensin II (Ang II)-induced cardiac dysfunction, as well as the proliferation and collagen production of primary cardiac fibroblasts. Total STAT3 expression, but not activation was stimulated by insulin; the effect of insulin on Ang II-induced fibrosis disappeared when STAT3 was blocked and could be entirely suppressed by the MEK inhibitor PD0325901. Our findings suggest a noninsulin-dependent glucose-lowering regimen for patients with type 2 diabetes (T2DM) and heart failure (HF).
研究领域:
心血管病学
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内分泌学
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分子生物学
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DOI
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Qing Ning,Yingxue Yue,Xinlian Liu,Wenbo Ji,Qin Zhao,Jing Wang,Zhenhai Zhang
S afe and effective treatments for psoriasis are limited. Anisole is an active ingredient in citrus and basil volatile oils; however, its potential for psoriasis treatment remains unexplored. To investigate the effects and mechanism of anisole transdermal administration as a treatment for psoriasis. Imiquimod (IMQ) was used to establish a C57 mouse psoriasis model. The severity of psoriasis lesions in each group was assessed by evaluating the thickness of skin lesions, erythema, and scales. Pathological changes within the epidermis organization were evaluated via hematoxylin and eosin (H&E) staining using light microscopy. Serum inflammatory factor levels were measured by enzyme-linked immunosorbent assays. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were performed to analyze the mRNA levels of relevant inflammatory factors and the expression of key proteins at the skin lesion sites in psoriatic mice. In model mice, applying anisole hydrogels significantly reduced the serum levels of pro-inflammatory factors interleukin (IL)-17A, (IL)-23, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. H&E staining revealed significantly attenuated stratum spinosum thickening and lymphocyte infiltration in the treatment group. RT-qPCR results further demonstrated that the skin tissues from the treatment group exhibited significantly reduced Il1b , Il17a , Il22 , and Tnfa mRNA expression. Western blotting revealed inhibition of the JAK1/STAT3 signaling pathway within anisole-treated psoriatic tissues. Anisole potentially reduces psoriatic-associated inflammation through the JAK1/STAT3 signaling pathway, alleviating IMQ-induced psoriasis.
研究领域:
皮肤病学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
·
2025
·
IF 3.1
Jiahui Sun,Luyao Shi,Fan Xu,Hanyan Sun,Yitong Liu,Jiangyun Sun,Qingxin Zhou
Colorectal cancer (CRC) is a worldwide health issue. It causes illness and death in millions of people each year. A positive correlation has been observed between the intake of dietary fat and the development of CRC. The composition of gut microbiota exhibits a significant correlation with pathophysiologic processes in intestine. Clinical treatment remains inadequate due to the complex pathogenic mechanisms of CRC triggered by a high-fat diet (HFD). Naringenin, a flavonoid from grapefruit, has anti-cancer activity. Our findings suggest that naringenin enhances gut microbiota diversity by increasing the abundance of beneficial bacterial species while reducing opportunistic pathogenic bacteria. The fecal microbiota transplantation assay (FMT) demonstrated that the anti-HFD-CRC activity of naringenin depended on the gut microbiota. Furthermore, naringenin antagonized the IL-6/STAT3 pathway. These results suggest that naringenin may be a potential treatment for HFD-CRC.
研究领域:
肿瘤学
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营养学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 16
·期 6
·9401-9408
·
IF 1.692
Yao‑Dong Chen,Yu Zhang,Tian‑Xiu Dong,Yu‑Tong Xu,Wei Zhang,Ting‑Ting An,Peng‑Fei Liu,Xiu‑Hua Yang
Malignant gliomas are a group of aggressive neoplasms among human cancers. The curative effects of current treatments are finite for improving the prognosis of patients. Hyperthermia (HT) is an effective treatment for cancers; however, the effects of HT with different temperatures in treatment of MG and relevant mechanisms remain unclear. MTT assay and Annexin V‑fluorescein isothiocyanate/propidium iodide staining were used for investigating the proliferation and apoptosis of C6 cells, respectively. Western blotting was applied to detect the expression of proteins. Ultrasonography was employed to evaluate the tumor formation rate, growth rate, angiogenesis rate and degree of hardness of tumors in vivo. The authors certified that HT with 42‑46˚C x 1 h, 1 t could inhibit proliferation, promote apoptosis, reduce tumor formation rate, growth rate, angiogenesis rate, degree of hardness of tumors, ischemic tolerance and anoxic tolerance, and have synergy with temozolomide in C6 cells. Long‑term HT (43˚C x 1 h, 1 t/5 d, 90 d) did not cut down the sensitivity of C6 cells to HT, and sustainably inhibited the proliferation of C6 cells. Furthermore, the authors proved HT produced these effects primarily through inhibition of the EGFR/STAT3/HIF‑1A/VEGF‑A pathway.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2018
·Vol. 17
·期 1
·652-659
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IF 1.664
Hongchao Han,Jie Xu,Weiwei Ji,Lisheng Wang,Aikun Wang
Transmembrane protein with epidermal growth factor (EGF)‑like and two follistatin motifs 2 (TMEFF2) is downregulated in human gastric cancer, and its levels are associated with tumor aggressiveness. Herein, a positive correlation was identified between serum vitamin C levels (µg/ml) and mRNA levels of TMEFF2 in gastric cancer tissue. TMEFF2 silencing promotes cell proliferation in GES‑1 normal human gastric epithelial cells and AGS human gastric adenocarcinoma cells. Notably, vitamin C and AG490 exerted antiproliferative effects on the two cell lines. The present study demonstrated that small interfering (si)‑RNA‑TMEFF2 exerts pro‑proliferative effects on GES‑1 and AGS cells. The results revealed that vitamin C significantly inhibited the growth of GES‑1 and AGS cells by reducing cell viability, decreasing the expression of proliferating cell nuclear antigen (PCNA), and blocking the STAT3 pathway. Moreover, siRNA‑TMEFF2‑induced enhanced cell viability and PCNA expression were significantly reversed by additional vitamin C treatment; notably, markedly enhanced TMEFF2 expression was observed. Upregulated TMEFF2 expression was observed in association with the antiproliferative effect of AG490. In conclusion, serum vitamin C content (µg/ml) was positively correlated with the mRNA levels of TMEFF2 in gastric cancer tissue. Exploring novel drugs that target TMEFF2 is a potential therapeutic strategy for blocking human GC.
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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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
Xiaoyun Yang,Yi Wang,Yujin Feng,Feng Wang,Lijuan Gao,Yueheng Wang
Myocardial infarction is often accompanied by symptoms of myocardial fibrosis, causing myocardial systolic and diastolic dysfunction. High levels of TMAO are considered to be strongly connected to cardiovascular diseases occurrence. The objective of this investigation was to determine whether formal TMAO affects the development of cardiac muscle fibers. The left anterior descending (LAD) coronary artery was ligated to construct myocardial infarction mouse model, while the control group mouse was only operated vessel separation. According to whether or not TMAO intervention is given, mice were divided into control, TMAO, myocardial infarction model(model), and myocardial infarction model + TMAO(model + TMAO). TMAO and model + TMAO group received 0.24 % TMAO in drinking water for one month. After modeling, echocardiography assessed cardiac function, and cardiac tissues were collected for analysis. Masson staining observed collagen deposition, while immunohistochemistry was conducted to identify fibronectin, collagen III, collagen I, and JAK/STAT pathway related proteins levels. In vitro, mouse cardiac fibroblasts were cultured and treated with varying TMAO concentrations (0, 300, 600, 900 μM), and Western blot was carried out to analyse changes in fibronectin, collagen III, and collagen I. Subsequently, the JAK2/STAT3 pathway inhibitor AG490 was utilized to treat cells and further examine the changes of fibronectin and collagen. The in vivo data showed TMAO significantly increases fibrosis and upregulates fibronectin, collagen III, and collagen I. In vitro experiments indicated that TMAO promotes fibronectin, collagen III, and collagen I levels through regulating the JAK2/STAT3 pathway, ultimately accelerating fibrosis.
研究领域:
心血管疾病研究
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分子生物学
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DOI
PubMed
高影响因子
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
·
2025
·Vol. 137
·期 1
·e70058
·
IF 3.3
Mengtian Pan,Xiang Li,Xinjuan Tian,Lele Zixin Yang,Weirong Fang
Ischemic stroke (IS) is one of the most sinister diseases and the second leading cause of death in the world. Eugenol (EUG) is a natural and biologically active component that can be extracted from various plants. Studies have found that EUG can alleviate middle cerebral artery occlusion and reperfusion (MCAO/R) injury in mice, but the specific mechanism remains vague. Tripartite motif protein 59 (TRIM59) is a member of TRIM protein family, a group of E3 ubiquitin ligases. In this article, we conducted both in vivo and in vitro experiments to determine the effect of EUG on ischemia–reperfusion injury and to explore the underlying mechanisms by manipulating the expression of TRIM59. Results showed that EUG alleviates acute injury and promotes functional repair of mouse IS by enhancing the phagocytosis of microglia through up-regulating the TRIM59, activating the STAT3 pathway and promoting the expression of CD11b.
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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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF HISTOCHEMISTRY
·
2022
·
IF 1.966
Haixia Li,Ning Su,Yaqiao Zhu,Wei Wang,Meihong Cai,Xiaohuan Luo,Wei Xia,Song Quan
Recurrent implantation failure (RIF) is defined as failure to achieve clinical pregnancy after at least 3 transfers of good-quality embryos by natural or artificial means. RIF is often a complex problem with a wide variety of etiologies and mechanisms as well as treatment options. In this study, using immunohistochemistry and Western blot, we demonstrated that the expression of leukemia inhibitory factor (LIF), Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3) was increased, while that of suppressor of cytokine signaling 1 (SOCS1) was decreased in RIF patients. Growth hormone (GH) administration proved to have positive effects on embryo implantation in RIF patients, but the action mechanism of GH has not been elucidated yet. To this aim, we studied the effects of GH on the proliferation in vitro of endometrial adenocarcinoma Ishikawa cells. GH stimulated the expression of LIF and SOCS1, and through SOCS1 inhibits the expression of phosphorylated STAT3, and finally inhibits the occurrence of RIF. Excessive phosphorylation of STAT can lead to decreased endometrial receptivity and abnormal embryo implantation. We also examined the effects of LIF overexpression and an LIF inhibitor (EC330) on the JAK/STAT pathway. LIF promoted cell proliferation, and the up-regulation of LIF increased the expression of SOCS1 and JAK1/STAT3 pathway-related genes in Ishikawa cells. As GH can inhibit the JAK1/STAT3 pathway through LIF, we hypothesize that upregulating SOCS1 may be a potential approach to treat RIF at the molecular level. GH can inhibit the JAK1/STAT3 pathway through LIF, up-regulating SOCS1 to treat RIF at the molecular level.
研究领域:
生殖生物学
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分子生物学
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内分泌学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 12
·5044-5053
·
IF 5.251
Zi-Fei Zhou,Tuan-Wei Sun,Yun-Hao Qin,Ying-Jie Zhu,Ying-Ying Jiang,Yang Zhang,Jun-Jian Liu,Jin Wu,Shi-Sheng He,Feng Chen
One-dimensional hydroxyapatite (HA) particularly mimics the structure of mineralized collagen fibrils and displays superior mechanical properties such as toughness. Herein, we report Se-doped HA/chitosan (Se-HA/CS) biopapers constructed with self-assembled Se-doped HA nanowires and chitosan. The Se-HA/CS biopapers with high flexibility and manufacturability can not only be further processed into arbitrary shapes by folding or using scissors but also display high performances in in vitro/vivo anti-bone tumor studies. The Se-HA/CS biopapers are more inclined to inhibit the growth of tumor cells (HCS 2/8 and SJSA cells) than that of normal human bone marrow stromal cells (hBMSCs). The potential mechanisms of this meaningful anti-tumor effect were investigated, such as reactive oxygen species accumulation and the activation of apoptosis and the underlying signal pathway involved (including caspase family, Bcl-2 family and JNK/STAT3). The results demonstrate that Se-HA/CS biopapers may inhibit the growth of HCS 2/8 and SJSA cells by synchronously inducing JNK activation and STAT3 inhibition and consequently promote the apoptosis of these cells. Furthermore, the in vivo anti-tumor studies confirm that the Se-HA/CS biopapers obviously suppress the growth of patient-derived xenograft tumor models.
研究领域:
材料科学
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生物材料
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2023
·
IF 5
Shao Xin,Li Jialong,Zhang Huidan,Zhang Xuhui,Sun Chongzhen,Ouyang Xin,Wang Yong,Wu Xiyang,Chen Chunbo
Although garlic polysaccharides have been found to possess anti-inflammatory activities, anti-inflammatory study on small molecule water-soluble garlic polysaccharide (WSGP) is few. In this study, a novel WSGP with a molecular weight of 1853 Da was isolated by DEAE-52 and Sephadex G-100 column and the chemical composition was identified by monosaccharide composition and methylation analysis. Furthermore, the antioxidant effects of WSGP and the potential molecular mechanisms on LPS-induced inflammatory responses in RAW264.7 macrophage cells were investigated. The results showed that WSGP has strong antioxidant activity, such as DPPH, hydroxyl, superoxide anion, ABTS radical scavenging capacity, Fe2+ chelating ability and reducing power. Meanwhile, WSGP could considerably suppress the manufacturing of NO and the mRNA and protein expression degrees of IL-6, TNF-α, and IL-1β in LPS inspired RAW264.7 macrophages WSGP could significantly suppress the production of NO and the mRNA and protein expression levels of IL-1β, IL-6, and TNF-α in LPS stimulated RAW264.7 macrophage cells (p < 0.05). In addition, the phosphorylated IκB-α, p65, and STAT3 proteins were significantly increased in LPS-induced macrophages, while this trend was significantly reversed by WSGP treatment in a concentration-dependent manner (p < 0.05). Consequently, WSGP supplementation might reduce LPS-induced inflammatory responses by suppressing proinflammatory cytokines and NF-κB and STAT3 pathway activation. The finding of this research would give scientific guidelines for the judicious use of small molecular garlic polysaccharide in anti-inflammatory treatments.
研究领域:
免疫学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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