SKIN RESEARCH AND TECHNOLOGY
·
2024
·
IF 2
Guiyu an Chen,Yingxun Chen,Yan Zhang,Shufeng Zheng,Louying Zhu,Mingxing Ding
Background Incontinence‐associated dermatitis (IAD) is a tough problem in clinical settings, not only increasing the risk of complications like catheter‐related urinary tract infections and pressure ulcers in elderly and critically ill patients, but also prolonging hospital stays, raising hospital costs, and possibly leading to medical disputes. This study is aimed to evaluate the therapeutic effect of silicone dressing combined with topical oxygen therapy on IAD in a rat model. Methods An IAD rat model induced by synthetic urine with trypsin was established. Hematoxylin & eosin staining was carried out to examine skin histology. Using immunofluorescence, the microvessel density in the affected skin tissues was determined. ELISA was performed to measure the concentrations of inflammatory cytokines and angiogenic factors in serum. The mRNA expression of EGF, PDGF, and VEGF was detected via qRT‐PCR. Western blotting was employed to determine NF‐κB p65/STAT1 pathway‐related protein levels. Results Compared to single therapy, silicone dressing combined with topical oxygen therapy could significantly reduce the severity of IAD, improve skin histology, inhibit inflammation, and promote angiogenesis in IAD rat models. Additionally, the results showed that relatively speaking, the combined therapy suppressed the NF‐κB p65/STAT1 signaling pathway more effectively. Conclusion These findings indicated that silicone dressing combined with topical oxygen therapy can alleviate IAD through promoting wound healing and inhibiting inflammation via NF‐κB p65/STAT1 signaling pathway in a rat model, which provided a theoretical basis for the prevention and treatment of IAD in clinic.
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2025
·
IF 7.3
Zixu Li,Yacan Gong,Emmanuel Sunday Okeke,Dan Li,Yao Chen,Weiwei Feng,Ting Zhao,Liuqing Yang,Guanghua Mao,Xiangyang Wu
Typical plasticizer dibutyl phthalate (DBP) has been demonstrated to induce hepatotoxicity in zebrafish, but the underlying molecular mechanisms remain incompletely elucidated. Numerous studies have shown that ferroptosis is involved in the pathophysiological progression of hepatic disease. However, it remains unclear whether ferroptosis is involved in the DBP-induced hepatotoxicity in zebrafish. Initially, histopathological analyses have preliminarily confirmed that DBP can activate inflammatory responses in the zebrafish liver. Further investigation revealed that DBP induces ferroptosis in the zebrafish liver, characterized by iron overload, lipid peroxidation, and aberrant activation of ferroptosis pathways. Furthermore, DBP exposure induced ferroptosis, disrupting cell membranes and subsequent release of HMGB1, which are sensed by immunocytes TLR4/NF-κB signaling pathways, thereby activating the innate immune response in a context-dependent manner. Moreover, the ferroptosis inhibitor Fer-1 effectively rescues the activation of HMGB1-TLR4/NF-κB-mediated immune processes. Overall, this work enriches the molecular mechanism of DBP-induced zebrafish liver inflammatory damage and provides a reliable biomarker for future environmental risk assessment of DBP.
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DOI
PubMed
高影响因子
POLYMER BULLETIN
·
2022
·Vol. 80
·期 7
·7519-7532
·
IF 2.843
Ma Yuan,Li Wen-Xia,Duan Li-Jun,Wang Li-An,Wu Yong-Gang
A new inorganic-organic hybrid heterometallic compound, namely {[(CH 3 ) 2 NH 2 ][CdNa(4,4′-bpdc) 2 ]} n ·6n(H 2 O) ( 1 , 4,4′-H 2 bpdc is 4,4′-biphenyldicarboxylic acid), was synthesized through the solvothermal self-assembly reactions of 4,4′-H 2 bpdc ligand in combination with Cd(II) and Na(I) salts. importantly, compound 1 shows high selectivity and sensitivity for the detection of acetylacetone (Hacac) molecule with a high K sv value of 11.667 nM −1 . Its prevention activity on osteoarthritis after the reconstruction of anterior cruciate ligament was investigated and the associated mechanism was analyzed. At first, the enzyme linked immunosorbent assay (ELISA) detection was implemented in the current research to detect the Interleukin-1β (IL-1β) and Interleukin-1β (IL-18) content released into joint cavity after treated with the compound. The results showed that this complex was good at inhibiting the IL-1β and IL-18 content released into joint cavity. The real time reverse transcription-polymerase chain reaction (RT-PCR) was carried out and the nuclear factor kappa-B (NF-κB) signaling pathway activation in joint soft tissue was tested exploiting real time RT-PCR. The real time RT-PCR exhibited that the NF-κB signaling pathway activation in the joint soft tissue was significantly reduced by the new compound. Subsequently, the levels of cartilage tissue cell apoptosis were also tested through Annexin V-FITC Apoptosis detection, and the results suggested the cartilage tissue cell apoptosis levels were obviously reduced by the compound.
研究领域:
材料科学
·
生物医学
·
化学
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DOI
高影响因子
ONCOGENE
·
2020
·Vol. 39
·期 37
·6024-6040
·
IF 7.971
Lin Binyan,Li Yongxu,Wang Tiepeng,Qiu Yangmin,Chen Zhenzhong,Zhao Kai,Lu Na
Metastatic breast cancer is characterized by high mortality and limited therapeutic target. During tumor metastasis, cytoskeletal reorganization is one of the key steps in the migration and invasion of breast cancer cells. Collapsin response mediator protein 2 (CRMP2) is a cytosolic phosphoprotein that plays an important role in regulating cytoskeletal dynamics. Previous researches have reported that altered CRMP2 expression is associated with breast cancer progression, but the underlying mechanism remains poorly understood. Here, we show that CRMP2 expression is reduced in various subtypes of breast cancers and negatively correlated with lymphatic metastasis. Overexpression of CRMP2 significantly inhibits invasion and stemness in breast cancer cells, while downregulation of CRMP2 promotes cell invasion, which is not required for tubulin polymerization. Mechanistic studies demonstrate that CRMP2 interacts with RECK, prevents RECK degradation, which, in turn, blocks NF-κB and Wnt signaling pathways. Furthermore, we find that phosphorylation of CRMP2 at T514 and S522 remarkably abolishes its functions to bind with RECK and to inhibit cell invasion. Pharmacologic rescue of CRMP2 expression suppressed breast cancer metastasis in vitro and in vivo and stimulated a synergetic effect with FN-1501 that induces CRMP2 dephosphorylation. Collectively, this study highlights the potential of CRMP2 as a therapeutic target in breast cancer metastasis and reveals a distinct mechanism of CRMP2.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
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PubMed
高影响因子
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
·
2016
·
IF 2.135
Wu Li,Minqiang Liu,Jianping Xie
The pathogenesis of tuberculosis, caused by Mycobacterium tuberculosis, is largely because of the pathogen's successful entry and survival within macrophages. We predicted that rv3369, a gene encoding a conserved protein, might play a role in the interactions with host cells. To test this, rv3369 gene was heterologously expressed in a nonpathogenic fast-growing Mycobacterium smegmatis strain. The recombinant strain survives better than the control within macrophages, accompanied by more host cell death and a marked higher secretion of interleukin-1β (IL-1β). Furthermore, pharmacological inhibition experiments showed that the NF-κB and ERK pathways were involved in the Rv3369-triggered IL-1β changes. These results provided evidence for the engagement of Rv3369 in the interaction between mycobacteria and host.
研究领域:
微生物学
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免疫学
·
感染病学
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分子生物学
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细胞生物学
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病原生物学
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DOI
高影响因子
Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
·
2024
·Vol. 34
·期 3
·637-646
·
IF 1.4
Guo Liyang,Xue Xuexue,Zhou Yang,Chen Chunli,Sheng Zunlai
Diarrhea continues to be a major public health problem and is thought to be the cause of 525,000 child fatalities annually. Studies have shown that Macleaya cordata (Willd.) R.Br., Papaveraceae, has a good therapeutic effect on diarrhea due to its action on ion channels. However, its antidiarrheal mechanisms and key targets are not supported by scientific research. This study aimed to identify the mechanisms of action and targets of the primary active antidiarrheal compounds of M. cordata . We used network pharmacology and molecular docking to identify the antidiarrheal mechanisms and the key targets of M. cordata and its main chemical constituents. Subsequently, the experiments performed with dihydrosanguinarine (25, 50, and 100 mg/kg), which included the evaluation of the inhibitory potential of the epidermal growth factor receptor in osimertinib-induced diarrhea, real-time quantitative PCR, and western blotting, were performed for further verification of its mechanism of action. The findings revealed that of all the genes, tyrosine-protein kinase Lck, receptor tyrosine-protein kinase Erbb2, and epidermal growth factor receptor had the highest capacity of action, and the NF-kappa B and the calcium signaling pathways may play essential roles in M. cordata against diarrhea. Dihydrosanguinarine is the most active ingredient, and it significantly inhibits the increase in incidence and decreased the fecal water content of osimertinib-induced diarrhea. Western blot and qRT-PCR showed that dihydrosanguinarine works as an antidiarrheal agent by upregulating the expression of the core target epidermal growth factor receptor, affecting the NF-kappa B and the calcium ion signaling pathways, downregulating the expression of calcium-activated chloride channel and NK-kappa B P-65. Graphical
研究领域:
药理学
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分子生物学
·
中药研究
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DOI
高影响因子
Biochemistry and Cell Biology
·
2021
·Vol. 99
·期 2
·
IF 3.626
Guangwei Liu,Wenxia Zhao,Jiameng Bai,Jianjiao Cui,Haowei Liang,Baoping Lu
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that seriously threatens the health of humans globally. Formononetin (FMN) is a natural herb extract with multiple biological functions. In this study, an experimental model of AIH was established in mice through the use of concanavalin A (ConA). To investigate the effects of FMN on ConA-induced hepatitis, the mice were pretreated with 50 or 100 mg/kg body mass of FMN. The results show that FMN alleviated ConA-induced liver injury of mice in a dose-dependent manner. Moreover, pretreatment with FMN inhibited the apoptosis of hepatocytes in the ConA-treated mice through downregulating the expression of pro-apoptotic proteins (Bax, cleaved caspase 9, and cleaved caspase 3) and upregulating the expression of anti-apoptotic protein (Bcl-2). It was also found that the levels of proinflammatory cytokines were greatly reduced in the serum and liver tissues of mice pretreated with FMN. Further studies showed that FMN reduced the level of phosphorylated nuclear factor kappa B (p-NF-κB) p65 and enhanced the level of IκBα (inhibitor of NF-κB), suggesting that FMN inhibits the activation of the NF-κB signaling pathway. In addition, FMN inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Therefore, FMN could be a promising agent for the treatment of AIH.
研究领域:
免疫学
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药理学
·
肝病学
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PubMed
高影响因子
Analytical Cellular Pathology
·
2021
·
IF 2.916
Xinwei Liu,Yue Zhou
Background. Long noncoding RNAs (lncRNAs) are dysregulated in periodontitis development and involved in osteogenesis. The current study was aimed at investigating the function of lncRNA ANRIL in periodontal ligament cells (PDLCs) and potential molecular mechanisms. Methods. Firstly, the level of ANRIL was tested by qPCR. Then, PDLCs were treated with a mineralizing solution to induce osteogenic differentiation. ALP activity was measured, and protein levels of BMP2, Osterix, and OCN were measured by Western blot. A target of ANRIL was verified using dual-luciferase reporter assay. miR-7 level was measured by qPCR, and the signals of the NF-κB pathway were tested by Western blot. Results. ANRIL expression was downregulated in PDL tissues. Next, ALP activity and protein levels of BMP2, Osterix, and OCN were increased to show that PDLCs were differentiated. ANRIL level was increased in differential PDLCs, in which knockdown inhibited osteogenic differentiation. Then, miR-7 was found as a target of ANRIL. The miR-7 level was upregulated in PDL tissues and reduced in differential PDLCs. Inhibition of miR-7 suppressed ALP activity and BMP2, Osterix, and OCN expression. Moreover, inhibition of miR-7 reversed the effects on the osteogenic differentiation induced by knockdown of ANRIL. Besides, the levels of p-P65 and p-IκBα were elevated by ANRIL downregulation and were rescued by suppressing miR-7. Conclusions. Knockdown of ANRIL inhibited osteogenic differentiation via sponging miR-7 through the NF-κB pathway, suggesting that ANRIL might be a therapeutic target for periodontitis.
研究领域:
分子生物学
·
口腔科学
·
牙周病学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Xiaoxiao Yang,Zhigang Liu,Mengyuan Fang,Tingfeng Zou,Zhen Zhang,Xianshe Meng,Tianxiang Wang,Huawen Meng,Yuanli Chen,Yajun Duan,Qingshan Li
Pterostilbene is a demethylated resveratrol derivative with attractive anti-inflammatory, anti-tumor and anti-oxidative stress activities. However, the clinical use of pterostilbene is limited by its poor selectivity and druggability. Heart failure is a leading cause of morbidity and mortality worldwide, which is closely related to enhanced oxidative stress and inflammation. There is an urgent need for new effective therapeutic drugs that can reduce oxidative stress and inflammatory responses. Therefore, we designed and synthesized a series of novel pterostilbene chalcone and dihydropyrazole derivatives with antioxidant and anti-inflammatory activities by the molecular hybridization strategy. The preliminary anti-inflammatory activities and structure-activity relationships of these compounds were evaluated by nitric oxide (NO) inhibitory activity in lipopolysaccharide (LPS)-treated RAW264.7 cells, and compound E1 exhibited the most potent anti-inflammatory activities. Furthermore, pretreatment with compound E1 decreased reactive oxygen species (ROS) generation both in RAW264.7 and H9C2 cells by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), as well as downstream antioxidant enzymes superoxide dismutase 1 (SOD1), catalase (CAT) and glutathione peroxidase 1 (GPX1). In addition, compound E1 also significantly inhibited LPS or doxorubicin (DOX)-induced inflammation in both RAW264.7 and H9C2 cells through reducing the expression of inflammatory cytokines by inhibiting nuclear factor-κB (NF-κB) signaling pathway . Moreover, we found that compound E1 improved DOX-induced heart failure by inhibiting inflammation and oxidative stress in mouse model, which is mediated by the potential of antioxidant and anti-inflammatory activities. In conclusion, this study demonstrated the novel pterostilbene dihydropyrazole derivative E1 was identified as a promising agent for heart failure treatment.
研究领域:
药理学
·
心脏病学
·
分子生物学
·
生物化学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2023
·
IF 5
Xiaoyong Dai,Yibo Hou,Ting Deng,Gaoyang Lin,Yuanxiong Cao,Guiyuan Yu,Wei Wei,Qing Zheng,Laiqiang Huang,Shaohua Ma
Triple-negative breast cancer (TNBC) is an aggressive cancer that poses a significant threat to women's health. Unfortunately, the lack of clinical targets leads the poor clinical outcomes in TNBC. Many cancers demonstrate overexpression of receptor for advanced glycation end products (RAGE), which can contribute to cancer progression. Despite the potential therapeutic value of blocking RAGE for TNBC treatment, effective peptide drugs have yet to be developed. In our study, we observed that RAGE was highly expressed in TNBC and was associated with poor disease progression. We subsequently investigated the antitumor effects and underlying mechanisms of the RAGE antagonist peptide RP7 in both in vitro and in vivo models of TNBC. Our study revealed that RP7 selectively binds to RAGE-overexpressing TNBC cell lines, including MDA-MB-231 and BT549, and significantly inhibits cell viability, migration, and invasion in both cell lines. Furthermore, RP7-treatment suppressed tumor growth in TNBC xenograft mouse models without inducing detectable toxicity in normal tissues. Mechanistically, RP7 was found to inhibit the phosphorylation of ERK1/2, IKKα/β, IKBα, and p65 to block the NF-κB pathway, prevent the entry of p65 into the nucleus, decrease the protein expression of Bcl-2 and HMGB1, and promote the release of cytochrome C from the mitochondria into the cytoplasm. These effects were observed to activate apoptosis and inhibit epithelial-mesenchymal transition (EMT) in TNBC cells. This study highlights RAGE as a candidate therapeutic target for TNBC treatment and suggests that the RAGE antagonist peptide RP7 is a promising anticancer drug for TNBC.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Liping Wang,Tiantian Ji,Ye Yuan,Haoyu Fu,Yang Wang,Shaobo Tian,Jia Hu,Lin Wang,Zheng Wang
The dramatically increasing incidence and prevalence of inflammatory bowel disease (IBD) are reportedly related to a Western diet, which is characterized by high sugar consumption. Dietary simple sugars aggravate IBD in animal models. However, the mechanisms underlying this effect remain unclear. Given that high-fructose corn syrup (HFCS) is a major added sugar in food and beverages, we focus on HFCS and investigated the effects of HFCS on a dextran sulfate sodium (DSS)-induced murine colitis model and in RAW264.7 macrophages. Our data demonstrate that short-term consumption of HFCS aggravates colitis and upregulates the proportion of macrophages in IBD mice but not in healthy mice. We find that HFCS promotes proinflammatory cytokine production through reactive oxygen species (ROS)-mediated nuclear factor-κB (NF-κB) signaling in RAW264.7 macrophages. Furthermore, N-acetylcysteine (NAC), an ROS scavenger, alleviates HFCS-aggravated colitis in mice and inhibits the ROS-mediated NF-κB signaling pathway in RAW264.7 macrophages. Our work unveils the important role of macrophages in HFCS-induced exacerbation of colitis and reveals the mechanism of how HFCS immunologically aggravates IBD.
研究领域:
免疫学
·
胃肠病学
·
营养学
·
分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Xin-Yu Shen,Jing-Mei Lu,Yu-Nan Lu,Guang-Nan Jin,Jing-Wen Ma,Jing-He Wang,Yu Wang,Xiang Xu,Lian-Xun Piao
Toxoplasma gondii ( T. gondii ) is an obligate intracellular protozoan parasite that causes pulmonary toxoplasmosis, although its pathogenesis is incompletely understood. There is no cure for toxoplasmosis. Coixol, a plant polyphenol extracted from coix seeds, has a variety of biological activities. However, the effects of coixol on T. gondii infection have not been clarified. In this study, we infected a mouse macrophage cell line (RAW 264.7) and BALB/c mice with the T. gondii RH strain to establish infection models in vitro and in vivo , respectively, to explore protective effects and potential mechanisms of coixol on lung injury caused by T. gondii infection. Anti- T. gondii effects and underlying anti-inflammatory mechanisms of coixol were investigated by real-time quantitative PCR, molecular docking, localized surface plasmon resonance, co-immunoprecipitation, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence microscopy. The results show that coixol inhibits T. gondii loads and T. gondii -derived heat shock protein 70 ( T.g. HSP70) expression. Moreover, coixol reduced inflammatory cell recruitment and infiltration, and ameliorated pathological lung injury induced by T. gondii infection. Coixol can directly bind T.g. HSP70 or Toll-like receptor 4 (TLR4) to disrupt their interaction. Coixol prevented overexpression of inducible nitric oxide synthase, tumor necrosis factor-α, and high mobility group box 1 by inhibiting activation of the TLR4/nuclear factor (NF)-κB signaling pathway, consistent with effects of the TLR4 inhibitor CLI-095. These results indicate that coixol improves T. gondii infection-induced lung injury by interfering with T.g. HSP70-mediated TLR4/NF-κB signaling. Altogether, these findings suggest that coixol is a promising effective lead compound for the treatment of toxoplasmosis.
研究领域:
寄生虫学
·
免疫学
·
药理学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
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