Pub Date : 2024-02-21DOI: 10.46439/signaling.2.025
Xiangpei Wang, Hongyun Liu, Xiaofen Li, Mei Zhang, Feng Xu, Mei Liu, Hongmei Wu
Hyperglycemia and renal fibrosis play critical roles in the occurrence and development of diabetic complications such as diabetic nephropathy (DN). Lupenone, a stable pentacyclic triterpenoid compound, has anti-hyperglycemic and anti-renal fibrosis activities. Previous research has confirmed that lupenone can improve renal fibrosis in type 2 diabetic nephropathy by regulating TGF-β/Smad/CTGF signaling pathway. However, the binding power of lupenone with its related targets has not been confirmed, and it is unclear whether it exerts anti-renal fibrosis effects as a prototype component. Therefore, the aim of this study was to identify the underlying mechanism of lupenone on anti-renal fibrosis based on the TGF-β/Smad/CTGF signaling pathway and elucidate their binding ability using molecular docking and in vitro cell experiments. Molecular docking results suggested that lupenone combined well with fibronectin, TGF-β1, TβRI, TβRII, Smad2, Smad3, Smad4, Smad7 and Smurf2, respectively. And lupenone could significantly reduce high glucose-induced MCs cytotoxicity. Furthermore, lupenone significantly downregulated the mRNA and protein expression of collagen-I, collagen-IV, fibronectin, TGF-β1, p-TβRI/TβRI, TβRII, p-Smad2/Smad2, p-Smad/Smad3, Smad4, Smurf2, and CTGF in high glucose-induced MCs, with the best effect observed in the high-dose lupenone group. These results concluded that lupenone could inhibit the generation of fibrosis factors collagen-I, collagen-IV, and fibronectin and delay the process of fibrosis by regulating the TGF-β/Smad/CTGF signaling pathway in MCs.
{"title":"Molecular docking combined with in vitro validation study to explore the effect of lupenone on alleviating renal fibrosis based on TGF-β/Smad/CTGF signaling pathway","authors":"Xiangpei Wang, Hongyun Liu, Xiaofen Li, Mei Zhang, Feng Xu, Mei Liu, Hongmei Wu","doi":"10.46439/signaling.2.025","DOIUrl":"https://doi.org/10.46439/signaling.2.025","url":null,"abstract":"Hyperglycemia and renal fibrosis play critical roles in the occurrence and development of diabetic complications such as diabetic nephropathy (DN). Lupenone, a stable pentacyclic triterpenoid compound, has anti-hyperglycemic and anti-renal fibrosis activities. Previous research has confirmed that lupenone can improve renal fibrosis in type 2 diabetic nephropathy by regulating TGF-β/Smad/CTGF signaling pathway. However, the binding power of lupenone with its related targets has not been confirmed, and it is unclear whether it exerts anti-renal fibrosis effects as a prototype component. Therefore, the aim of this study was to identify the underlying mechanism of lupenone on anti-renal fibrosis based on the TGF-β/Smad/CTGF signaling pathway and elucidate their binding ability using molecular docking and in vitro cell experiments. Molecular docking results suggested that lupenone combined well with fibronectin, TGF-β1, TβRI, TβRII, Smad2, Smad3, Smad4, Smad7 and Smurf2, respectively. And lupenone could significantly reduce high glucose-induced MCs cytotoxicity. Furthermore, lupenone significantly downregulated the mRNA and protein expression of collagen-I, collagen-IV, fibronectin, TGF-β1, p-TβRI/TβRI, TβRII, p-Smad2/Smad2, p-Smad/Smad3, Smad4, Smurf2, and CTGF in high glucose-induced MCs, with the best effect observed in the high-dose lupenone group. These results concluded that lupenone could inhibit the generation of fibrosis factors collagen-I, collagen-IV, and fibronectin and delay the process of fibrosis by regulating the TGF-β/Smad/CTGF signaling pathway in MCs.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"4 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140443451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-05DOI: 10.46439/signaling.2.029
Jiayu Yu, Juan Zheng, Chaodong Wu
{"title":"An essential role for hepatocyte adenosine kinase in regulating fat metabolism and inflammation","authors":"Jiayu Yu, Juan Zheng, Chaodong Wu","doi":"10.46439/signaling.2.029","DOIUrl":"https://doi.org/10.46439/signaling.2.029","url":null,"abstract":"","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"238 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140461366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-19DOI: 10.46439/signaling.2.026
Elizondo Gm, Raymond A, Perez-Vasquez C, Dafny N
Currently, methylphenidate (MPD) is one of the most commonly prescribed psychostimulants for management and treatment of attention deficit hyperactivity disorder (ADHD). A rise in the consumption of MPD by “ordinary” youth and adults prompted concern regarding the ontogeny effects of acute and chronic MPD exposure. The objective of this study is to concomitantly record behavioral and neuronal activity from the dorsal raphe (DR) nucleus, a major source of serotonergic innervation in the mammalian brain before and following different doses of acute and chronic administration of MPD in freely behaving adolescent (young) and adult rats previously implanted with electrodes in the DR. A wireless recording system over 10 consecutive experimental days was used. Four experimental groups were used: saline, 0.6, 2.5, and 10.0 mg/kg MPD for young and similar groups for adult rats. Animals received one daily MPD injection on experimental days 1-6, followed by three washout days, and then drug rechallenge on experimental day 10 (ED10). 860 DR units were recorded, 356 from adult rats and 504 from young rats. The study provides experimental evidence that the responses to acute and chronic MPD were significantly different between the two age groups. Moreover, the study implies that it is essential to evaluate the electrophysiological responses to a drug based on the animal’s behavioral response to chronic drug exposure and that the DR and serotonin signaling has a significant role in the response to MPD as well as a different role in young as compared to adult rats.
{"title":"Methylphenidate (Ritalin) affects serotonin signaling differently in young compared to adults. Concomitant behavioral and neuronal recording from dorsal raphe in freely behaving rats","authors":"Elizondo Gm, Raymond A, Perez-Vasquez C, Dafny N","doi":"10.46439/signaling.2.026","DOIUrl":"https://doi.org/10.46439/signaling.2.026","url":null,"abstract":"Currently, methylphenidate (MPD) is one of the most commonly prescribed psychostimulants for management and treatment of attention deficit hyperactivity disorder (ADHD). A rise in the consumption of MPD by “ordinary” youth and adults prompted concern regarding the ontogeny effects of acute and chronic MPD exposure. The objective of this study is to concomitantly record behavioral and neuronal activity from the dorsal raphe (DR) nucleus, a major source of serotonergic innervation in the mammalian brain before and following different doses of acute and chronic administration of MPD in freely behaving adolescent (young) and adult rats previously implanted with electrodes in the DR. A wireless recording system over 10 consecutive experimental days was used. Four experimental groups were used: saline, 0.6, 2.5, and 10.0 mg/kg MPD for young and similar groups for adult rats. Animals received one daily MPD injection on experimental days 1-6, followed by three washout days, and then drug rechallenge on experimental day 10 (ED10). 860 DR units were recorded, 356 from adult rats and 504 from young rats. The study provides experimental evidence that the responses to acute and chronic MPD were significantly different between the two age groups. Moreover, the study implies that it is essential to evaluate the electrophysiological responses to a drug based on the animal’s behavioral response to chronic drug exposure and that the DR and serotonin signaling has a significant role in the response to MPD as well as a different role in young as compared to adult rats.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"442 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140502597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-21DOI: 10.46439/signaling.2.021
Weili Sun
Cancer remains a significant global health challenge, with researchers continually striving to unravel the complexities of its development and progression. In recent years, CD226, also known as DNAM-1, has emerged as a key player in cancer biology. Its noteworthy potential as both a therapeutic target and a novel biomarker has been evident in predicting cancer patient prognosis, assessing levels of immune infiltration, and gauging responses to immunotherapy. This commentary aims to illuminate the multifarious functions of CD226 in cancer, delving into its impact on tumor progression, its influence on the immune response, its potential as a therapeutic target, and the persisting enigmas that drive ongoing research efforts in this domain.
{"title":"Unlocking the significance of CD226 in cancer","authors":"Weili Sun","doi":"10.46439/signaling.2.021","DOIUrl":"https://doi.org/10.46439/signaling.2.021","url":null,"abstract":"Cancer remains a significant global health challenge, with researchers continually striving to unravel the complexities of its development and progression. In recent years, CD226, also known as DNAM-1, has emerged as a key player in cancer biology. Its noteworthy potential as both a therapeutic target and a novel biomarker has been evident in predicting cancer patient prognosis, assessing levels of immune infiltration, and gauging responses to immunotherapy. This commentary aims to illuminate the multifarious functions of CD226 in cancer, delving into its impact on tumor progression, its influence on the immune response, its potential as a therapeutic target, and the persisting enigmas that drive ongoing research efforts in this domain.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"39 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138950123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-21DOI: 10.46439/signaling.2.023
Sunil Palani, Keer Sun
{"title":"Commentary: Interferons in Influenza and Streptococcus Pneumoniae co-pathogenesis","authors":"Sunil Palani, Keer Sun","doi":"10.46439/signaling.2.023","DOIUrl":"https://doi.org/10.46439/signaling.2.023","url":null,"abstract":"","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"57 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138950728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-21DOI: 10.46439/signaling.2.024
May-Lucie Meyer, Fred R. Hirsch
Targeting EGFR has a long history in the treatment of non-small cell lung cancer (NSCLC). It was around the 2000s that it was reported that EGFR protein expression increased with bronchial dysplasia in high-risk smokers and patients with lung cancer. However, EGFR inhibitors were not effective in unselected patients with advanced NSCLC. After the identification of sensitizing EGFR mutations, tyrosine kinase inhibitors became the cornerstone of treatment for patients with EGFR-mutated NSCLC. However, other drugs were developed to target EGFR in the EGFR-wild type population, such as monoclonal antibodies. Cetuximab is an anti-EGFR monoclonal antibody, and has been a focus over the past two decades. Though not approved in NSCLC due to marginal and inconsistent effects in phase 3 trials, research aimed to discover biomarkers to identify a subgroup of the population that might benefit. This includes a composite score that evaluates histology, immunohistochemistry, and gene copy amplification. This article reviews the history of the development and discontinuation of monoclonal antibodies in NSCLC and discusses the role of biomarkers in the treatment of advanced EGFR-wild type NSCLC.
{"title":"Biomarkers for monoclonal antibody targeting EGFR in NSCLC: Challenges, current status, and future perspectives","authors":"May-Lucie Meyer, Fred R. Hirsch","doi":"10.46439/signaling.2.024","DOIUrl":"https://doi.org/10.46439/signaling.2.024","url":null,"abstract":"Targeting EGFR has a long history in the treatment of non-small cell lung cancer (NSCLC). It was around the 2000s that it was reported that EGFR protein expression increased with bronchial dysplasia in high-risk smokers and patients with lung cancer. However, EGFR inhibitors were not effective in unselected patients with advanced NSCLC. After the identification of sensitizing EGFR mutations, tyrosine kinase inhibitors became the cornerstone of treatment for patients with EGFR-mutated NSCLC. However, other drugs were developed to target EGFR in the EGFR-wild type population, such as monoclonal antibodies. Cetuximab is an anti-EGFR monoclonal antibody, and has been a focus over the past two decades. Though not approved in NSCLC due to marginal and inconsistent effects in phase 3 trials, research aimed to discover biomarkers to identify a subgroup of the population that might benefit. This includes a composite score that evaluates histology, immunohistochemistry, and gene copy amplification. This article reviews the history of the development and discontinuation of monoclonal antibodies in NSCLC and discusses the role of biomarkers in the treatment of advanced EGFR-wild type NSCLC.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"135 49","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138953352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-21DOI: 10.46439/signaling.2.022
Yuyue Zuo, Yueqi Zhang, Lei Dai
Angiopoietin-like 4 (ANGPTL4) belongs to the angiopoietin-like protein family and mediates the inhibition of lipoprotein lipase activity. Emerging evidence suggests that ANGPTL4 has pleiotropic functions with anti- and pro-inflammatory properties. Here, we have reviewed the research progress on ANGPTL4 and systematically discussed the dual role of ANGPTL4 in inflammation and inflammatory diseases. Understanding the potential mechanisms of ANGPTL4 in inflammation will aid in drug discovery and treatment development.
{"title":"Friend or foe? The elusive role of ANGPTL4 in inflammation","authors":"Yuyue Zuo, Yueqi Zhang, Lei Dai","doi":"10.46439/signaling.2.022","DOIUrl":"https://doi.org/10.46439/signaling.2.022","url":null,"abstract":"Angiopoietin-like 4 (ANGPTL4) belongs to the angiopoietin-like protein family and mediates the inhibition of lipoprotein lipase activity. Emerging evidence suggests that ANGPTL4 has pleiotropic functions with anti- and pro-inflammatory properties. Here, we have reviewed the research progress on ANGPTL4 and systematically discussed the dual role of ANGPTL4 in inflammation and inflammatory diseases. Understanding the potential mechanisms of ANGPTL4 in inflammation will aid in drug discovery and treatment development.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"54 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138949525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-28DOI: 10.46439/signaling.1.020
Suridh Adhikari, A. Azhdarinia, M. Kolonin
Progression to metastases remains the overriding cause of cancer-associated mortality. Metastatic cancer is not amenable to surgery and its treatment is further complicated by the development of therapy resistance often observed at advanced cancer stages. Early detection of metastases is therefore critical but has been limited by the lack of probes that can effectively localize them. Similar challenges persist with therapeutics specifically targeting metastasized cancer cells. Thus, agents that specifically target disseminating tumor cells at an early stage could produce new theranostic applications and be transformative for the survival of patients with advanced cancers. Recent studies have described new approaches for early detection and targeted eradication of metastatic cancer. Here we summarize the results from preclinical validation of the experimental probes reported to date.
{"title":"Probes for cancer metastasis imaging and therapeutic targeting","authors":"Suridh Adhikari, A. Azhdarinia, M. Kolonin","doi":"10.46439/signaling.1.020","DOIUrl":"https://doi.org/10.46439/signaling.1.020","url":null,"abstract":"Progression to metastases remains the overriding cause of cancer-associated mortality. Metastatic cancer is not amenable to surgery and its treatment is further complicated by the development of therapy resistance often observed at advanced cancer stages. Early detection of metastases is therefore critical but has been limited by the lack of probes that can effectively localize them. Similar challenges persist with therapeutics specifically targeting metastasized cancer cells. Thus, agents that specifically target disseminating tumor cells at an early stage could produce new theranostic applications and be transformative for the survival of patients with advanced cancers. Recent studies have described new approaches for early detection and targeted eradication of metastatic cancer. Here we summarize the results from preclinical validation of the experimental probes reported to date.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139225021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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