Traditional aluminum hydroxide is widely used as a vaccine adjuvant. Despite its favorable safety profile, it can cause an inflammatory response at the injection sites. However, multiple studies have shown that aluminum hydroxide nanoparticles have more potent adjuvant activity than their traditional aluminum hydroxide counterparts as antigen carriers; it has also been found that the local inflammation caused by aluminum hydroxide nanoparticle adjuvants is milder than that of other adjuvants. The aim of the present study was to compare the degree of inflammatory response between the aluminum hydroxide nanoparticle adjuvants and the traditional aluminum hydroxide adjuvants in the desensitization treatment of a mouse model of house dust mite (HDM)-induced allergic asthma. Mice were sensitized intraperitoneally with HDM. Subcutaneous desensitization was performed with PBS, traditional aluminum hydroxide adjuvants and aluminum hydroxide nanoparticle adjuvants. The mice were challenged and subsequently euthanized. The skin tissue at the local injection sites was assessed and specific indices were measured, such as the response of specific immunoglobulins, the airway hyper-responsiveness (AHR), and the inflammation in the bronchoalveolar lavage and lung tissues. Early hypersensitivity responses were suppressed in mice treated with subcutaneous immunotherapy (SCIT). Both traditional aluminum hydroxide-SCIT and aluminum hydroxide nanoparticle-SCIT could inhibit AHR. However, aluminum hydroxide nanoparticle-SCIT was able to significantly inhibit the secretion of eosinophils in the lung tissue and the production of type 2 cytokine Interleukin (IL)-5 in blood compared with the corresponding effects noted by traditional aluminum hydroxide adjuvants. Moreover, the aluminum hydroxide nanoparticle group reduced the inflammatory response at the local injection site. Collectively, the data indicated that allergen-specific immunotherapy using aluminum hydroxide nanoparticle adjuvants reduces lung and local inflammation compared with traditional aluminum hydroxide adjuvants.
{"title":"Aluminum hydroxide nanoparticle adjuvants can reduce the inflammatory response more efficiently in a mouse model of allergic asthma than traditional aluminum hydroxide adjuvants.","authors":"Yue Zeng, Weikang Zhou","doi":"10.3892/etm.2023.12327","DOIUrl":"https://doi.org/10.3892/etm.2023.12327","url":null,"abstract":"Traditional aluminum hydroxide is widely used as a vaccine adjuvant. Despite its favorable safety profile, it can cause an inflammatory response at the injection sites. However, multiple studies have shown that aluminum hydroxide nanoparticles have more potent adjuvant activity than their traditional aluminum hydroxide counterparts as antigen carriers; it has also been found that the local inflammation caused by aluminum hydroxide nanoparticle adjuvants is milder than that of other adjuvants. The aim of the present study was to compare the degree of inflammatory response between the aluminum hydroxide nanoparticle adjuvants and the traditional aluminum hydroxide adjuvants in the desensitization treatment of a mouse model of house dust mite (HDM)-induced allergic asthma. Mice were sensitized intraperitoneally with HDM. Subcutaneous desensitization was performed with PBS, traditional aluminum hydroxide adjuvants and aluminum hydroxide nanoparticle adjuvants. The mice were challenged and subsequently euthanized. The skin tissue at the local injection sites was assessed and specific indices were measured, such as the response of specific immunoglobulins, the airway hyper-responsiveness (AHR), and the inflammation in the bronchoalveolar lavage and lung tissues. Early hypersensitivity responses were suppressed in mice treated with subcutaneous immunotherapy (SCIT). Both traditional aluminum hydroxide-SCIT and aluminum hydroxide nanoparticle-SCIT could inhibit AHR. However, aluminum hydroxide nanoparticle-SCIT was able to significantly inhibit the secretion of eosinophils in the lung tissue and the production of type 2 cytokine Interleukin (IL)-5 in blood compared with the corresponding effects noted by traditional aluminum hydroxide adjuvants. Moreover, the aluminum hydroxide nanoparticle group reduced the inflammatory response at the local injection site. Collectively, the data indicated that allergen-specific immunotherapy using aluminum hydroxide nanoparticle adjuvants reduces lung and local inflammation compared with traditional aluminum hydroxide adjuvants.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"3 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
[This retracts the article DOI: 10.3892/etm.2014.2074.].
[本文撤消了文章 DOI：10.3892/etm.2014.2074.]。
{"title":"[Retracted] Inhibitory effect of Puerariae radix flavones on platelet‑derived growth factor‑BB‑induced proliferation of vascular smooth muscle cells via PI3K and ERK pathways.","authors":"Hui Li, Kaijun Luo, Juan Hou","doi":"10.3892/etm.2023.12323","DOIUrl":"https://doi.org/10.3892/etm.2023.12323","url":null,"abstract":"[This retracts the article DOI: 10.3892/etm.2014.2074.].","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"16 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Local ulcerative cutaneous hemorrhage resulting from breast cancer profoundly effects the quality of life of patients, at times even posing a threat to life. While early diagnosis rates of breast cancer have shown improvement, some patients may present at an advanced stage upon consultation. Presently, there is no standardized treatment approach for these patients. In this context, the present study presented two case studies detailing the use of interventional embolization chemotherapy for addressing severe local ulcerative hemorrhage associated with breast cancer. Post-treatment, there was a notable amelioration in the mammary ulceration among the patients, an elevated hemoglobin level compared with baseline and a consequent enhancement in their overall quality of life. These cases may serve as valuable references for the management of such clinical situations.
{"title":"Interventional chemoembolization for the treatment of severe ulcerative bleeding caused by advanced breast cancer: A report of two cases.","authors":"Xing Wei, Hong-Chao Zhang, Yue-He Tu, Xiang Li, Wei-Sheng Wu","doi":"10.3892/etm.2023.12324","DOIUrl":"https://doi.org/10.3892/etm.2023.12324","url":null,"abstract":"Local ulcerative cutaneous hemorrhage resulting from breast cancer profoundly effects the quality of life of patients, at times even posing a threat to life. While early diagnosis rates of breast cancer have shown improvement, some patients may present at an advanced stage upon consultation. Presently, there is no standardized treatment approach for these patients. In this context, the present study presented two case studies detailing the use of interventional embolization chemotherapy for addressing severe local ulcerative hemorrhage associated with breast cancer. Post-treatment, there was a notable amelioration in the mammary ulceration among the patients, an elevated hemoglobin level compared with baseline and a consequent enhancement in their overall quality of life. These cases may serve as valuable references for the management of such clinical situations.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bo Zhou, Liyuan Zhao, Xinfeng Xing, Hai Wang, Asihati Kuwantai, Kai Chen
Endoscopic retrograde cholangiopancreatography (ERCP) has become a common treatment method for common bile duct stones. However, ERCP is also associated with a high risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). Identification of risk factors is essential for reducing the incidence of PEP. The present study aimed to summarize the risk factors for PEP by performing a meta-analysis. Therefore, studies published between 2000 and 2022 were screened in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Digital Periodicals and the Weipu Database, with no language restrictions. Newcastle-Ottawa Scale was used to assess the quality of the included studies. Stata 17.0 software was utilized for the meta-analysis of 14 possible risk factors. Overall, 15 high-quality studies were included into the present meta-analysis. The results showed that female [odds ratio (OR), 1.42; 95% CI, 1.23-1.64), age <60 years (OR, 1.53; 95% CI, 1.06-2.21), difficult intubation (OR, 4.87; 95% CI, 2.73-8.68), ≥3 cannulation attempts (OR, 9.64; 95% CI, 4.16-22.35), cannulation time ≥10 min (OR, 2.37; 95% CI, 1.67-3.35), history of pancreatitis (OR, 2.95; 95% CI, 1.06-5.51), pancreatic duct visualization (OR, 3.63; 95% CI, 2.47-5.34) and sphincter of Oddi dysfunction (OR, 5.72; 95% CI, 1.80-18.24) are potential risk factors for PEP (P<0.05). In conclusion, the present meta-analysis suggests that PEP can be affected by several risk factors, particularly the technique-related factors such as the frequency and time of cannulation. Therefore, effective precautions should be taken as early as possible to reduce the incidence of PEP.
内镜逆行胰胆管造影术（ERCP）已成为治疗胆总管结石的常用方法。然而，ERCP 也与内镜逆行胰胆管造影术后胰腺炎（PEP）的高风险相关。识别风险因素对于降低 PEP 的发生率至关重要。本研究旨在通过荟萃分析总结 PEP 的风险因素。因此，本研究在 PubMed、Cochrane Library、Embase、Web of Science、中国国家知识基础设施、万方数字期刊和维普数据库中筛选了 2000 年至 2022 年间发表的研究，语言不限。采用纽卡斯尔-渥太华量表评估纳入研究的质量。使用 Stata 17.0 软件对 14 个可能的风险因素进行了荟萃分析。本次荟萃分析共纳入了 15 项高质量研究。结果显示，女性[几率比（OR），1.42；95% CI，1.23-1.64]、年龄<60 岁（OR，1.53；95% CI，1.06-2.21）、插管困难（OR，4.87；95% CI，2.73-8.68）、插管尝试≥3 次（OR，9.64；95% CI，4.16-22.35）、插管时间≥10 分钟（OR，2.37；95% CI，1.67-3.35）、胰腺炎病史（OR，2.95；95% CI，1.06-5.51）、胰管可视化（OR，3.63；95% CI，2.47-5.34）和 Oddi括约肌功能障碍（OR，5.72；95% CI，1.80-18.24）是 PEP 的潜在危险因素（P<0.05）。总之，本荟萃分析表明，PEP 可受多种风险因素的影响，尤其是与插管频率和时间等技术相关的因素。因此，应尽早采取有效的预防措施以降低 PEP 的发生率。
{"title":"Risk factors for post‑retrograde cholangiopancreatography pancreatitis in patients with common bile duct stones: A meta‑analysis.","authors":"Bo Zhou, Liyuan Zhao, Xinfeng Xing, Hai Wang, Asihati Kuwantai, Kai Chen","doi":"10.3892/etm.2023.12320","DOIUrl":"https://doi.org/10.3892/etm.2023.12320","url":null,"abstract":"Endoscopic retrograde cholangiopancreatography (ERCP) has become a common treatment method for common bile duct stones. However, ERCP is also associated with a high risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). Identification of risk factors is essential for reducing the incidence of PEP. The present study aimed to summarize the risk factors for PEP by performing a meta-analysis. Therefore, studies published between 2000 and 2022 were screened in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Digital Periodicals and the Weipu Database, with no language restrictions. Newcastle-Ottawa Scale was used to assess the quality of the included studies. Stata 17.0 software was utilized for the meta-analysis of 14 possible risk factors. Overall, 15 high-quality studies were included into the present meta-analysis. The results showed that female [odds ratio (OR), 1.42; 95% CI, 1.23-1.64), age <60 years (OR, 1.53; 95% CI, 1.06-2.21), difficult intubation (OR, 4.87; 95% CI, 2.73-8.68), ≥3 cannulation attempts (OR, 9.64; 95% CI, 4.16-22.35), cannulation time ≥10 min (OR, 2.37; 95% CI, 1.67-3.35), history of pancreatitis (OR, 2.95; 95% CI, 1.06-5.51), pancreatic duct visualization (OR, 3.63; 95% CI, 2.47-5.34) and sphincter of Oddi dysfunction (OR, 5.72; 95% CI, 1.80-18.24) are potential risk factors for PEP (P<0.05). In conclusion, the present meta-analysis suggests that PEP can be affected by several risk factors, particularly the technique-related factors such as the frequency and time of cannulation. Therefore, effective precautions should be taken as early as possible to reduce the incidence of PEP.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"9 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genomic instability is an essential hallmark of cancer, and cellular DNA damage response (DDR) defects drive tumorigenesis by disrupting genomic stability. Several studies have identified abnormalities in DDR-associated genes, and a dysfunctional ubiquitin-proteasome system (UPS) is the most common molecular event in metastatic castration-resistant prostate cancer (PCa). For example, mutations in Speckle-type BTB/POZ protein-Ser119 result in DDR downstream target activation deficiency. Skp2 excessive upregulation inhibits homologous recombination repair and promotes cell growth and migration. Abnormally high expression of a deubiquitination enzyme, ubiquitin-specific protease 12, stabilizes E3 ligase MDM2, which further leads to p53 degradation, causing DDR interruption and genomic instability. In the present review, the basic pathways of DDR, UPS dysfunction, and its induced DDR alterations mediated by genomic instability, and especially the potential application of UPS and DDR alterations as biomarkers and therapeutic targets in PCa treatment, were described.
{"title":"Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review).","authors":"Yan Lin, Xiaofeng Jin","doi":"10.3892/etm.2023.12321","DOIUrl":"https://doi.org/10.3892/etm.2023.12321","url":null,"abstract":"Genomic instability is an essential hallmark of cancer, and cellular DNA damage response (DDR) defects drive tumorigenesis by disrupting genomic stability. Several studies have identified abnormalities in DDR-associated genes, and a dysfunctional ubiquitin-proteasome system (UPS) is the most common molecular event in metastatic castration-resistant prostate cancer (PCa). For example, mutations in Speckle-type BTB/POZ protein-Ser119 result in DDR downstream target activation deficiency. Skp2 excessive upregulation inhibits homologous recombination repair and promotes cell growth and migration. Abnormally high expression of a deubiquitination enzyme, ubiquitin-specific protease 12, stabilizes E3 ligase MDM2, which further leads to p53 degradation, causing DDR interruption and genomic instability. In the present review, the basic pathways of DDR, UPS dysfunction, and its induced DDR alterations mediated by genomic instability, and especially the potential application of UPS and DDR alterations as biomarkers and therapeutic targets in PCa treatment, were described.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"18 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone remodeling is tightly controlled by various factors, including hormones, autacoids and cytokines. Among them, oncostatin M (OSM) is a multifunctional cytokine produced by osteal macrophages, which serves as an essential modulator of bone remodeling. Macrophage colony-stimulating factor (M-CSF) and osteoprotegerin are secreted by osteoblasts, and also have pivotal roles in the regulation of the bone remodeling process. The binding of basic fibroblast growth factor (bFGF), a key regulator of bone remodeling, to the corresponding receptor [fibroblast growth factor receptor (FGFR)] triggers the dimerization and activation of FGFRs, which causes the phosphorylation of FGFR substrates and subsequent activation of downstream effectors, including mitogen-activated protein kinases (MAPKs), via Grb2. bFGF can activate MAPKs, resulting in the synthesis of osteoprotegerin and vascular endothelial growth factor in osteoblast-like MC3T3-E1 cells. In the present study, the effects of OSM on bFGF-induced osteoblast activation were investigated in the synthesis of osteoprotegerin and M-CSF in osteoblasts. The release of osteoprotegerin and M-CSF were analyzed using ELISA. The mRNA expression levels of osteoprotegerin and M-CSF were analyzed using reverse transcription-quantitative PCR. Phosphorylation of p38 MAPK, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p44/p42 MAPK was assessed using western blotting. OSM enhanced bFGF-induced osteoprotegerin release and bFGF-stimulated mRNA expression of osteoprotegerin. By contrast, OSM suppressed the bFGF-induced release of M-CSF and bFGF-stimulated mRNA expression of M-CSF. SB203580, a p38 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, suppressed the bFGF-stimulated M-CSF release, whereas PD98059, an upstream kinase inhibitor of p44/p42 MAPK, failed to suppress the M-CSF release stimulated by bFGF. Furthermore, OSM enhanced the bFGF-induced phosphorylation of p38 MAPK, but attenuated the bFGF-stimulated phosphorylation of SAPK/JNK. By contrast, OSM had little effect on the bFGF-induced phosphorylation of p44/p42 MAPK. SB203580 markedly reduced the amplification of bFGF-stimulated osteoprotegerin release enhanced by OSM. These results strongly suggested that OSM may possess divergent effects on bFGF-induced osteoblast activation, upregulation of p38 MAPK and downregulation of SAPK/JNK, leading to the amplification of osteoprotegerin synthesis and the attenuation of M-CSF synthesis.
{"title":"Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells.","authors":"Tomoyuki Hioki, Junko Tachi, Kyohei Ueda, Rie Matsushima-Nishiwaki, Hiroki Iida, Osamu Kozawa, Haruhiko Tokuda","doi":"10.3892/etm.2023.12322","DOIUrl":"https://doi.org/10.3892/etm.2023.12322","url":null,"abstract":"Bone remodeling is tightly controlled by various factors, including hormones, autacoids and cytokines. Among them, oncostatin M (OSM) is a multifunctional cytokine produced by osteal macrophages, which serves as an essential modulator of bone remodeling. Macrophage colony-stimulating factor (M-CSF) and osteoprotegerin are secreted by osteoblasts, and also have pivotal roles in the regulation of the bone remodeling process. The binding of basic fibroblast growth factor (bFGF), a key regulator of bone remodeling, to the corresponding receptor [fibroblast growth factor receptor (FGFR)] triggers the dimerization and activation of FGFRs, which causes the phosphorylation of FGFR substrates and subsequent activation of downstream effectors, including mitogen-activated protein kinases (MAPKs), via Grb2. bFGF can activate MAPKs, resulting in the synthesis of osteoprotegerin and vascular endothelial growth factor in osteoblast-like MC3T3-E1 cells. In the present study, the effects of OSM on bFGF-induced osteoblast activation were investigated in the synthesis of osteoprotegerin and M-CSF in osteoblasts. The release of osteoprotegerin and M-CSF were analyzed using ELISA. The mRNA expression levels of osteoprotegerin and M-CSF were analyzed using reverse transcription-quantitative PCR. Phosphorylation of p38 MAPK, stress-activated protein kinase/c<i>-</i>Jun N-terminal kinase (SAPK/JNK) and p44/p42 MAPK was assessed using western blotting. OSM enhanced bFGF-induced osteoprotegerin release and bFGF-stimulated mRNA expression of osteoprotegerin. By contrast, OSM suppressed the bFGF-induced release of M-CSF and bFGF-stimulated mRNA expression of M-CSF. SB203580, a p38 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, suppressed the bFGF-stimulated M-CSF release, whereas PD98059, an upstream kinase inhibitor of p44/p42 MAPK, failed to suppress the M-CSF release stimulated by bFGF. Furthermore, OSM enhanced the bFGF-induced phosphorylation of p38 MAPK, but attenuated the bFGF-stimulated phosphorylation of SAPK/JNK. By contrast, OSM had little effect on the bFGF-induced phosphorylation of p44/p42 MAPK. SB203580 markedly reduced the amplification of bFGF-stimulated osteoprotegerin release enhanced by OSM. These results strongly suggested that OSM may possess divergent effects on bFGF-induced osteoblast activation, upregulation of p38 MAPK and downregulation of SAPK/JNK, leading to the amplification of osteoprotegerin synthesis and the attenuation of M-CSF synthesis.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"3 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiankun Quan, Xinxin Ma, Ming Li, Xi Li, Haifeng Yuan
β-Amyloid peptide (Aβ) deposition in the brain is an important pathological change in Alzheimer's disease (AD). Insulin-degrading enzyme (IDE), which is regulated transcriptionally by peroxisome proliferator-activated receptor γ (PPARγ), is able to proteolyze Aβ. One of the members of the MAPK family, ERK, is able to mediate the phosphorylation of PPARγ at Ser112, thereby inhibiting its transcriptional activity. Ginsenoside Rg1 is one of the active ingredients in the natural medicine ginseng and has inhibitory effects on Aβ production. The present study was designed to investigate whether ginsenoside Rg1 is able to affect the regulation of PPARγ based on the expression of its target gene, IDE, and whether it is able to promote Aβ degradation via inhibition of the ERK/PPARγ phosphorylation pathway. In the present study, primary cultured rat hippocampal neurons were treated with Aβ1-42, ginsenoside Rg1 and the ERK inhibitor PD98059, and subsequently TUNEL staining was used to detect the level of neuronal apoptosis. ELISA was subsequently employed to detect the intra- and extracellular Aβ1-42 levels, immunofluorescence staining and western blotting were used to detect the translocation of ERK from the cytoplasm to the nucleus, immunofluorescence double staining was used to detect the co-expression of ERK and PPARγ, and finally, western blotting was used to detect the phosphorylation of PPARγ at Ser112 and IDE expression. The results demonstrated that ginsenoside Rg1 or PD98059 were able to inhibit primary cultured hippocampal neuron apoptosis induced by Aβ1-42 treatment, reduce the levels of intra- and extraneuronal Aβ1-42 and inhibit the translocation of ERK from the cytoplasm to the nucleus. Furthermore, administration of ginsenoside Rg1 or PD98059 resulted in attenuated co-expression of ERK and PPARγ, inhibition of phosphorylation of PPARγ at Ser112 mediated by ERK and an increase in IDE expression. In addition, the effects when PD98059 to inhibit ERK followed by treatment with ginsenoside Rg1 were found to be more pronounced than those when using PD98059 alone. In conclusion, ginsenoside Rg1 was demonstrated to exert neuroprotective effects on AD via inhibition of the ERK/PPARγ phosphorylation pathway, which led to an increase in IDE expression, the promotion of Aβ degradation and the decrease of neuronal apoptosis. These results could provide a theoretical basis for the clinical application of ginsenoside Rg1 in AD.
{"title":"Ginsenoside Rg1 promotes β‑amyloid peptide degradation through inhibition of the ERK/PPARγ phosphorylation pathway in an Alzheimer's disease neuronal model.","authors":"Qiankun Quan, Xinxin Ma, Ming Li, Xi Li, Haifeng Yuan","doi":"10.3892/etm.2023.12319","DOIUrl":"https://doi.org/10.3892/etm.2023.12319","url":null,"abstract":"β-Amyloid peptide (Aβ) deposition in the brain is an important pathological change in Alzheimer's disease (AD). Insulin-degrading enzyme (IDE), which is regulated transcriptionally by peroxisome proliferator-activated receptor γ (PPARγ), is able to proteolyze Aβ. One of the members of the MAPK family, ERK, is able to mediate the phosphorylation of PPARγ at Ser112, thereby inhibiting its transcriptional activity. Ginsenoside Rg1 is one of the active ingredients in the natural medicine ginseng and has inhibitory effects on Aβ production. The present study was designed to investigate whether ginsenoside Rg1 is able to affect the regulation of PPARγ based on the expression of its target gene, <i>IDE</i>, and whether it is able to promote Aβ degradation via inhibition of the ERK/PPARγ phosphorylation pathway. In the present study, primary cultured rat hippocampal neurons were treated with Aβ<sub>1-42</sub>, ginsenoside Rg1 and the ERK inhibitor PD98059, and subsequently TUNEL staining was used to detect the level of neuronal apoptosis. ELISA was subsequently employed to detect the intra- and extracellular Aβ<sub>1-42</sub> levels, immunofluorescence staining and western blotting were used to detect the translocation of ERK from the cytoplasm to the nucleus, immunofluorescence double staining was used to detect the co-expression of ERK and PPARγ, and finally, western blotting was used to detect the phosphorylation of PPARγ at Ser112 and IDE expression. The results demonstrated that ginsenoside Rg1 or PD98059 were able to inhibit primary cultured hippocampal neuron apoptosis induced by Aβ<sub>1-42</sub> treatment, reduce the levels of intra- and extraneuronal Aβ<sub>1-42</sub> and inhibit the translocation of ERK from the cytoplasm to the nucleus. Furthermore, administration of ginsenoside Rg1 or PD98059 resulted in attenuated co-expression of ERK and PPARγ, inhibition of phosphorylation of PPARγ at Ser112 mediated by ERK and an increase in IDE expression. In addition, the effects when PD98059 to inhibit ERK followed by treatment with ginsenoside Rg1 were found to be more pronounced than those when using PD98059 alone. In conclusion, ginsenoside Rg1 was demonstrated to exert neuroprotective effects on AD via inhibition of the ERK/PPARγ phosphorylation pathway, which led to an increase in IDE expression, the promotion of Aβ degradation and the decrease of neuronal apoptosis. These results could provide a theoretical basis for the clinical application of ginsenoside Rg1 in AD.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"65 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Echinacoside (ECH) is a compound derived from the natural herbs Cistanche and Echinacea, which has considerable protective effects on heart failure (HF). HF is characterized by myocardial damage and abnormal ferroptosis. Glutathione peroxidase 4 (GPX4) is an important regulator of ferroptosis, which plays a role in ferroptosis-related diseases. Despite this, the therapeutic mechanisms of ECH against HF remain unknown. Therefore, the aim of the present study was to investigate the cardioprotective effect and underlying mechanisms of ECH in the treatment of doxorubicin (DOX)-induced chronic HF (CHF). Cell proliferation was assessed using a CCK-8 assay. Furthermore, cardiac cell injury and oxidative stress were determined by measuring the lactate dehydrogenase (LDH), malondialdehyde (MDA), and glutathione (GSH) levels. The levels of Fe2+ and lipid reactive oxygen species (ROS), and expression of the biomarkers of ferroptosis, including GPX4 and prostaglandin-endoperoxide synthase 2 (PTGS2), were measured to examine cardiomyocyte ferroptosis. Additionally, RNA interference was used to silence Gpx4. In vitro and in vivo, ECH considerably reduced the MDA and LDH levels and increased the GSH level, thereby attenuating DOX-induced cardiac injury and oxidative stress. Meanwhile, ECH treatment decreased the lipid ROS levels and PTGS2 expression while increasing GPX4 expression, thereby alleviating DOX-induced cardiomyocyte ferroptosis. Moreover, knockdown of Gpx4 inhibited the protective effects of ECH on DOX-induced accumulation of lipid ROS in cardiomyocytes. These findings indicate that ECH can reduce DOX-induced cardiac injury by inhibiting ferroptosis via GPX4, highlighting its value as a potentially valuable therapeutic target in the management of CHF.
{"title":"Echinacoside ameliorates doxorubicin‑induced cardiac injury by regulating GPX4 inhibition‑induced ferroptosis.","authors":"Yan Ma, Xiaoli Yang, Nianxin Jiang, Cheng Lu, Jiehan Zhang, Shaowei Zhuang","doi":"10.3892/etm.2023.12317","DOIUrl":"https://doi.org/10.3892/etm.2023.12317","url":null,"abstract":"Echinacoside (ECH) is a compound derived from the natural herbs <i>Cistanche</i> and <i>Echinacea</i>, which has considerable protective effects on heart failure (HF). HF is characterized by myocardial damage and abnormal ferroptosis. Glutathione peroxidase 4 (GPX4) is an important regulator of ferroptosis, which plays a role in ferroptosis-related diseases. Despite this, the therapeutic mechanisms of ECH against HF remain unknown. Therefore, the aim of the present study was to investigate the cardioprotective effect and underlying mechanisms of ECH in the treatment of doxorubicin (DOX)-induced chronic HF (CHF). Cell proliferation was assessed using a CCK-8 assay. Furthermore, cardiac cell injury and oxidative stress were determined by measuring the lactate dehydrogenase (LDH), malondialdehyde (MDA), and glutathione (GSH) levels. The levels of Fe<sup>2+</sup> and lipid reactive oxygen species (ROS), and expression of the biomarkers of ferroptosis, including GPX4 and prostaglandin-endoperoxide synthase 2 (PTGS2), were measured to examine cardiomyocyte ferroptosis. Additionally, RNA interference was used to silence <i>Gpx4</i>. <i>In vitro</i> and <i>in vivo</i>, ECH considerably reduced the MDA and LDH levels and increased the GSH level, thereby attenuating DOX-induced cardiac injury and oxidative stress. Meanwhile, ECH treatment decreased the lipid ROS levels and PTGS2 expression while increasing GPX4 expression, thereby alleviating DOX-induced cardiomyocyte ferroptosis. Moreover, knockdown of <i>Gpx4</i> inhibited the protective effects of ECH on DOX-induced accumulation of lipid ROS in cardiomyocytes. These findings indicate that ECH can reduce DOX-induced cardiac injury by inhibiting ferroptosis via GPX4, highlighting its value as a potentially valuable therapeutic target in the management of CHF.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"128 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhou Sun, Kejing Zhu, Guofu Liang, Fu Yan, Sheng Chao, Lei Jia, Yulin Niu
The effect of vitamin K on clinical outcomes in patients receiving kidney transplantation is contested according to previous studies. This meta-analysis aimed to summarize the impact of vitamin K on all-cause mortality, renal function, inflammation, and vascular/bone health in patients receiving kidney transplantation. EMBASE, PubMed, and Cochrane were searched for literature concerning the effect of vitamin K on clinical outcomes of patients receiving kidney transplantation until December 2022. Normal vitamin K status/vitamin K supplementation was considered as the experimental group; while vitamin K deficiency/no vitamin K supplementation was considered as the control group. All-cause mortality, renal function indexes, C-reactive protein (CRP), and vascular/bone health indexes were extracted and analyzed. A total of seven studies with 1,101 patients in the experimental group and 651 patients in the control group were included. All-cause mortality was decreased in the experimental group vs. the control group [relative risk (95% confidence interval (CI)]: 0.72 (0.60-0.86), P<0.001]. Regarding renal function indexes, the estimated glomerular filtration rate was increased in the experimental group vs. the control group [mean difference (95% CI): 9.87 (1.48-18.26), P=0.021]; while creatinine and albumin remained unchanged between the two groups (both P>0.05). Moreover, CRP, systolic blood pressure, diastolic blood pressure, triglycerides, hemoglobin, calcium, and 25-hydroxyvitamin D were unchanged between the two groups (all P>0.05). Publication bias was low, and the robustness assessed by sensitivity analysis was generally acceptable. Thus vitamin K exerted a potential implication in reducing all-cause mortality and improving renal function in patients receiving kidney transplantation.
根据以往的研究，维生素 K 对肾移植患者临床预后的影响存在争议。本荟萃分析旨在总结维生素 K 对肾移植患者全因死亡率、肾功能、炎症和血管/骨骼健康的影响。在 EMBASE、PubMed 和 Cochrane 中检索了截至 2022 年 12 月有关维生素 K 对肾移植患者临床结果影响的文献。将维生素 K 状态正常/补充维生素 K 的患者视为实验组；维生素 K 缺乏/未补充维生素 K 的患者视为对照组。研究人员提取并分析了全因死亡率、肾功能指数、C反应蛋白（CRP）和血管/骨骼健康指数。共纳入七项研究，其中实验组有 1,101 名患者，对照组有 651 名患者。实验组与对照组相比，全因死亡率有所下降[相对风险（95% 置信区间（CI）]：0.72（0.60-0.86），P<0.001]。在肾功能指标方面，实验组与对照组相比，估计肾小球滤过率有所增加[平均差异（95% CI）：9.87 (1.48-18.26)，P=0.021]；而两组间肌酐和白蛋白保持不变（均为 P>0.05）。此外，两组间的 CRP、收缩压、舒张压、甘油三酯、血红蛋白、钙和 25- 羟维生素 D 均无变化（均为 P>0.05）。发表偏倚较低，敏感性分析评估的稳健性基本可以接受。因此，维生素 K 在降低肾移植患者的全因死亡率和改善肾功能方面具有潜在意义。
{"title":"Effect of vitamin K on improving post‑kidney transplant outcomes: a meta‑analysis.","authors":"Zhou Sun, Kejing Zhu, Guofu Liang, Fu Yan, Sheng Chao, Lei Jia, Yulin Niu","doi":"10.3892/etm.2023.12318","DOIUrl":"https://doi.org/10.3892/etm.2023.12318","url":null,"abstract":"The effect of vitamin K on clinical outcomes in patients receiving kidney transplantation is contested according to previous studies. This meta-analysis aimed to summarize the impact of vitamin K on all-cause mortality, renal function, inflammation, and vascular/bone health in patients receiving kidney transplantation. EMBASE, PubMed, and Cochrane were searched for literature concerning the effect of vitamin K on clinical outcomes of patients receiving kidney transplantation until December 2022. Normal vitamin K status/vitamin K supplementation was considered as the experimental group; while vitamin K deficiency/no vitamin K supplementation was considered as the control group. All-cause mortality, renal function indexes, C-reactive protein (CRP), and vascular/bone health indexes were extracted and analyzed. A total of seven studies with 1,101 patients in the experimental group and 651 patients in the control group were included. All-cause mortality was decreased in the experimental group vs. the control group [relative risk (95% confidence interval (CI)]: 0.72 (0.60-0.86), P<0.001]. Regarding renal function indexes, the estimated glomerular filtration rate was increased in the experimental group vs. the control group [mean difference (95% CI): 9.87 (1.48-18.26), P=0.021]; while creatinine and albumin remained unchanged between the two groups (both P>0.05). Moreover, CRP, systolic blood pressure, diastolic blood pressure, triglycerides, hemoglobin, calcium, and 25-hydroxyvitamin D were unchanged between the two groups (all P>0.05). Publication bias was low, and the robustness assessed by sensitivity analysis was generally acceptable. Thus vitamin K exerted a potential implication in reducing all-cause mortality and improving renal function in patients receiving kidney transplantation.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"35 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atopic dermatitis (AD) is a common inflammatory skin condition and the leading cause of morbidity associated with skin conditions worldwide. For the majority of patients, AD is a lifelong disease that cannot be cured completely. Therefore, in the present study, differentially expressed genes (DEGs) in the epidermal immune microenvironment were screened using bioinformatic techniques. Subsequently, an in vitro cellular model was constructed to investigate the role of microRNA (miR)-155 in immune infiltration during AD. In the present study, two datasets (GSE121212 and GSE157194) were downloaded from Gene Expression Omnibus, before the DEGs were screened and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses. miRNet was used to predict the possible target genes of miR-155 among the differentially expressed genes found. Consequently, peptidase inhibitor 3 (PI3), FOS-like 1, AP-1 transcription factor subunit (FOSL1), C-X-C motif chemokine ligand (CXCL)1 and CXCL8 were selected to be the potential target genes of miR-155 in the epidermal immune microenvironment of patients with AD. Concurrently, an inflammatory cell model using HaCaT cells was constructed by TNF-α and IFN-γ treatment. The effects of miR-155 on HaCaT cell proliferation and secretion of IL-1β, IL-6, IL-10, IL-15, PI3, FOSL1, CXCL1 and CXCL8 under inflammatory and non-inflammatory conditions were then analyzed. The results showed that after the HaCaT cells were transfected with miR-155, miR-155 inhibited HaCaT cell proliferation and decreased the mRNA expression levels of PI3 and CXCL8, increased the mRNA levels of FOSL1 and secretion levels of IL-1β, IL-6, IL-15 and CXCL1. By contrast, miR-155 decreased the secretion levels of IL-10 and CXCL8. In the inflammatory cell model of HaCaT cells, miR-155 was found to significantly inhibit the proliferation of HaCaT cells during inflammation whilst significantly increasing the secretion of IL-1β, IL-6, IL-10 and IL-15. In addition, miR-155 increased the mRNA expression and secretion levels of CXCL1 and CXCL8, whilst also increasing the mRNA expression levels of PI3. Results from the current study suggest that miR-155 can stimulate keratinocytes to produce inflammatory cytokines and proteins to enhance the inflammatory response in AD.
{"title":"Identification of potential miR‑155 target genes in epidermal immune microenvironment of atopic dermatitis patients and their inflammatory effects on HaCaT cells.","authors":"Xiaochen Wang, Lu Chen, Xiaoqing Chen, Chang Liu, Wenhong Qiu, Kaiwen Guo","doi":"10.3892/etm.2023.12313","DOIUrl":"https://doi.org/10.3892/etm.2023.12313","url":null,"abstract":"Atopic dermatitis (AD) is a common inflammatory skin condition and the leading cause of morbidity associated with skin conditions worldwide. For the majority of patients, AD is a lifelong disease that cannot be cured completely. Therefore, in the present study, differentially expressed genes (DEGs) in the epidermal immune microenvironment were screened using bioinformatic techniques. Subsequently, an <i>in vitro</i> cellular model was constructed to investigate the role of microRNA (miR)-155 in immune infiltration during AD. In the present study, two datasets (GSE121212 and GSE157194) were downloaded from Gene Expression Omnibus, before the DEGs were screened and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses. miRNet was used to predict the possible target genes of miR-155 among the differentially expressed genes found. Consequently, peptidase inhibitor 3 (PI3), FOS-like 1, AP-1 transcription factor subunit (FOSL1), C-X-C motif chemokine ligand (CXCL)1 and CXCL8 were selected to be the potential target genes of miR-155 in the epidermal immune microenvironment of patients with AD. Concurrently, an inflammatory cell model using HaCaT cells was constructed by TNF-α and IFN-γ treatment. The effects of miR-155 on HaCaT cell proliferation and secretion of IL-1β, IL-6, IL-10, IL-15, PI3, FOSL1, CXCL1 and CXCL8 under inflammatory and non-inflammatory conditions were then analyzed. The results showed that after the HaCaT cells were transfected with miR-155, miR-155 inhibited HaCaT cell proliferation and decreased the mRNA expression levels of PI3 and CXCL8, increased the mRNA levels of FOSL1 and secretion levels of IL-1β, IL-6, IL-15 and CXCL1. By contrast, miR-155 decreased the secretion levels of IL-10 and CXCL8. In the inflammatory cell model of HaCaT cells, miR-155 was found to significantly inhibit the proliferation of HaCaT cells during inflammation whilst significantly increasing the secretion of IL-1β, IL-6, IL-10 and IL-15. In addition, miR-155 increased the mRNA expression and secretion levels of CXCL1 and CXCL8, whilst also increasing the mRNA expression levels of PI3. Results from the current study suggest that miR-155 can stimulate keratinocytes to produce inflammatory cytokines and proteins to enhance the inflammatory response in AD.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"1 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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