Y. Xiong, Lang Chen, Tao Yu, Chenchen Yan, Wu Zhou, Faqi Cao, Xiaomeng You, Yingqi Zhang, Yun Sun, Jing Liu, Hang Xue, Yiqiang Hu, Dong Chen, B. Mi, Guohui Liu
{"title":"Correction for: Inhibition of circulating exosomal microRNA-15a-3p accelerates diabetic wound repair","authors":"Y. Xiong, Lang Chen, Tao Yu, Chenchen Yan, Wu Zhou, Faqi Cao, Xiaomeng You, Yingqi Zhang, Yun Sun, Jing Liu, Hang Xue, Yiqiang Hu, Dong Chen, B. Mi, Guohui Liu","doi":"10.18632/aging.205514","DOIUrl":"https://doi.org/10.18632/aging.205514","url":null,"abstract":"","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"39 11","pages":"6627 - 6628"},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140701904","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}
Anbang He, S. He, Cong Huang, Zhicong Chen, Yucai Wu, Y. Gong, Xuesong Li, Liqun Zhou
This article has been corrected: It was found that there is the overlap between the images showing migration and invasion of Caki-1-shMTDH-KD1-MTDH cells in Figure 3J. The authors confirmed that the image of transwell invasion of Caki-1-shMTDH-KD1-MTDH cells was misplaced during the figure layout. They provided the original images of the transwell assays and corrected Figure 3J with the proper image obtained from the original data. The authors also would like to clarify the use of the same western blot images in Figures 3D and 4E , depicting MTDH and β -actin expression in 786-O-shMTDH-#1 cells. The purpose was to demonstrate the efficacy of MTDH overexpression in lentivirus-infected
本文已作更正：发现图 3J 中显示 Caki-1-shMTDH-KD1-MTDH 细胞迁移和侵袭的图像有重叠。作者确认，在排版时，Caki-1-shMTDH-KD1-MTDH 细胞的经孔侵袭图像放错了位置。他们提供了经孔实验的原始图像，并用从原始数据中获得的正确图像修正了图 3J。作者还希望澄清图 3D 和图 4E 中使用了相同的 Western 印迹图像，描述了 786-O-shMTDH-#1 细胞中 MTDH 和 β -actin 的表达。目的是证明 MTDH 在慢病毒感染的
{"title":"Correction for: MTDH promotes metastasis of clear cell renal cell carcinoma by activating SND1-mediated ERK signaling and epithelial-mesenchymal transition","authors":"Anbang He, S. He, Cong Huang, Zhicong Chen, Yucai Wu, Y. Gong, Xuesong Li, Liqun Zhou","doi":"10.18632/aging.205603","DOIUrl":"https://doi.org/10.18632/aging.205603","url":null,"abstract":"This article has been corrected: It was found that there is the overlap between the images showing migration and invasion of Caki-1-shMTDH-KD1-MTDH cells in Figure 3J. The authors confirmed that the image of transwell invasion of Caki-1-shMTDH-KD1-MTDH cells was misplaced during the figure layout. They provided the original images of the transwell assays and corrected Figure 3J with the proper image obtained from the original data. The authors also would like to clarify the use of the same western blot images in Figures 3D and 4E , depicting MTDH and β -actin expression in 786-O-shMTDH-#1 cells. The purpose was to demonstrate the efficacy of MTDH overexpression in lentivirus-infected","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"49 29","pages":"6629 - 6630"},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140701326","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}
Gastric cancer presents a formidable challenge, marked by its debilitating nature and often dire prognosis. Emerging evidence underscores the pivotal role of tumor stem cells in exacerbating treatment resistance and fueling disease recurrence in gastric cancer. Thus, the identification of genes contributing to tumor stemness assumes paramount importance. Employing a comprehensive approach encompassing ssGSEA, WGCNA, and various machine learning algorithms, this study endeavors to delineate tumor stemness key genes (TSKGs). Subsequently, these genes were harnessed to construct a prognostic model, termed the Tumor Stemness Risk Genes Prognostic Model (TSRGPM). Through PCA, Cox regression analysis and ROC curve analysis, the efficacy of Tumor Stemness Risk Scores (TSRS) in stratifying patient risk profiles was underscored, affirming its ability as an independent prognostic indicator. Notably, the TSRS exhibited a significant correlation with lymph node metastasis in gastric cancer. Furthermore, leveraging algorithms such as CIBERSORT to dissect immune infiltration patterns revealed a notable association between TSRS and monocytes and other cell. Subsequent scrutiny of tumor stemness risk genes (TSRGs) culminated in the identification of CDC25A for detailed investigation. Bioinformatics analyses unveil CDC25A’s implication in driving the malignant phenotype of tumors, with a discernible impact on cell proliferation and DNA replication in gastric cancer. Noteworthy validation through in vitro experiments corroborated the bioinformatics findings, elucidating the pivotal role of CDC25A expression in modulating tumor stemness in gastric cancer. In summation, the established and validated TSRGPM holds promise in prognostication and delineation of potential therapeutic targets, thus heralding a pivotal stride towards personalized management of this malignancy.
胃癌是一项艰巨的挑战，其特点是使人衰弱，预后往往很糟糕。新的证据强调，肿瘤干细胞在加剧胃癌耐药性和助长疾病复发方面起着关键作用。因此，鉴定导致肿瘤干细胞的基因至关重要。本研究采用了一种包含ssGSEA、WGCNA和各种机器学习算法的综合方法，致力于确定肿瘤干性关键基因（TSKGs）。随后，这些基因被用来构建预后模型，即肿瘤干性风险基因预后模型（TSRGPM）。通过 PCA、Cox 回归分析和 ROC 曲线分析，肿瘤干性风险评分（TSRS）在患者风险分层方面的功效得到了强调，肯定了其作为独立预后指标的能力。值得注意的是，TSRS 与胃癌淋巴结转移有显著相关性。此外，利用 CIBERSORT 等算法剖析免疫浸润模式，发现 TSRS 与单核细胞和其他细胞之间存在显著关联。随后对肿瘤干性风险基因（TSRGs）进行了仔细研究，最终确定了CDC25A，并对其进行了详细调查。生物信息学分析揭示了 CDC25A 在驱动肿瘤恶性表型方面的作用，它对胃癌的细胞增殖和 DNA 复制有明显的影响。值得注意的是，体外实验的验证证实了生物信息学的发现，阐明了 CDC25A 的表达在调节胃癌肿瘤干性中的关键作用。总之，已建立并通过验证的 TSRGPM 有望用于预后判断和潜在治疗目标的确定，从而预示着胃癌的个性化治疗将迈出关键的一步。
{"title":"Machine learning for identifying tumor stemness genes and developing prognostic model in gastric cancer","authors":"Guo-Xing Li, Yun-Peng Chen, You-Yang Hu, Wen-Jing Zhao, Yun-Yan Lu, Fu-Jian Wan, Zhi-Jun Wu, Xiang-Qian Wang, Qi-Ying Yu","doi":"10.18632/aging.205715","DOIUrl":"https://doi.org/10.18632/aging.205715","url":null,"abstract":"Gastric cancer presents a formidable challenge, marked by its debilitating nature and often dire prognosis. Emerging evidence underscores the pivotal role of tumor stem cells in exacerbating treatment resistance and fueling disease recurrence in gastric cancer. Thus, the identification of genes contributing to tumor stemness assumes paramount importance. Employing a comprehensive approach encompassing ssGSEA, WGCNA, and various machine learning algorithms, this study endeavors to delineate tumor stemness key genes (TSKGs). Subsequently, these genes were harnessed to construct a prognostic model, termed the Tumor Stemness Risk Genes Prognostic Model (TSRGPM). Through PCA, Cox regression analysis and ROC curve analysis, the efficacy of Tumor Stemness Risk Scores (TSRS) in stratifying patient risk profiles was underscored, affirming its ability as an independent prognostic indicator. Notably, the TSRS exhibited a significant correlation with lymph node metastasis in gastric cancer. Furthermore, leveraging algorithms such as CIBERSORT to dissect immune infiltration patterns revealed a notable association between TSRS and monocytes and other cell. Subsequent scrutiny of tumor stemness risk genes (TSRGs) culminated in the identification of CDC25A for detailed investigation. Bioinformatics analyses unveil CDC25A’s implication in driving the malignant phenotype of tumors, with a discernible impact on cell proliferation and DNA replication in gastric cancer. Noteworthy validation through in vitro experiments corroborated the bioinformatics findings, elucidating the pivotal role of CDC25A expression in modulating tumor stemness in gastric cancer. In summation, the established and validated TSRGPM holds promise in prognostication and delineation of potential therapeutic targets, thus heralding a pivotal stride towards personalized management of this malignancy.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"8 16","pages":"6455 - 6477"},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140710074","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}
Tursunay Dilxat, Qiang Shi, Xiaofan Chen, Xuxin Liu
Acute lung injury (ALI) is a major cause of acute respiratory failure with a high morbidity and mortality rate, and effective therapeutic strategies for ALI remain limited. Inflammatory response is considered crucial for the pathogenesis of ALI. Garlic, a globally used cooking spice, reportedly exhibits excellent anti-inflammatory bioactivity. However, protective effects of garlic against ALI have never been reported. This study aimed to investigate the protective effects of garlic oil (GO) supplementation on lipopolysaccharide (LPS)-induced ALI models. Hematoxylin and eosin staining, pathology scores, lung myeloperoxidase (MPO) activity measurement, lung wet/dry (W/D) ratio detection, and bronchoalveolar lavage fluid (BALF) analysis were performed to investigate ALI histopathology. Real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were conducted to evaluate the expression levels of inflammatory factors, nuclear factor-κB (NF-κB), NLRP3, pyroptosis-related proteins, and H2S-producing enzymes. GO attenuated LPS-induced pulmonary pathological changes, lung W/D ratio, MPO activity, and inflammatory cytokines in the lungs and BALF. Additionally, GO suppressed LPS-induced NF-κB activation, NLRP3 inflammasome expression, and inflammatory-related pyroptosis. Mechanistically, GO promoted increased H2S production in lung tissues by enhancing the conversion of GO-rich polysulfide compounds or by increasing the expression of H2S-producing enzymes in vivo. Inhibition of endogenous or exogenous H2S production reversed the protective effects of GO on ALI and eliminated the inhibitory effects of GO on NF-κB, NLRP3, and pyroptotic signaling pathways. Overall, these findings indicate that GO has a critical anti-inflammatory effect and protects against LPS-induced ALI by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.
急性肺损伤（ALI）是急性呼吸衰竭的主要病因，发病率和死亡率都很高，但针对急性肺损伤的有效治疗策略仍然有限。炎症反应被认为是急性肺损伤发病机制的关键。据报道，大蒜作为一种全球通用的烹饪香料，具有极佳的抗炎生物活性。然而，大蒜对 ALI 的保护作用却从未被报道过。本研究旨在探讨补充大蒜油（GO）对脂多糖（LPS）诱导的 ALI 模型的保护作用。研究人员通过血沉和伊红染色、病理学评分、肺髓过氧化物酶（MPO）活性测定、肺干湿比（W/D）检测和支气管肺泡灌洗液（BALF）分析来研究 ALI 组织病理学。实时聚合酶链反应、Western 印迹和酶联免疫吸附试验评估了炎症因子、核因子-κB（NF-κB）、NLRP3、热蛋白相关蛋白和 H2S 产酶的表达水平。GO 可减轻 LPS 引起的肺部病理变化、肺 W/D 比率、MPO 活性以及肺和 BALF 中的炎性细胞因子。此外，GO 还能抑制 LPS 诱导的 NF-κB 激活、NLRP3 炎性体表达和与炎症相关的脓毒症。从机理上讲，GO 通过增强富含 GO 的多硫化合物的转化或增加体内 H2S 生成酶的表达，促进了肺组织中 H2S 生成的增加。抑制内源性或外源性H2S的产生逆转了GO对ALI的保护作用，并消除了GO对NF-κB、NLRP3和裂解信号通路的抑制作用。总之，这些研究结果表明，GO 具有重要的抗炎作用，可通过产生 H2S 来抑制 NF-κB/NLRP3 信号通路，从而防止 LPS 诱导的 ALI。
{"title":"Garlic oil supplementation blocks inflammatory pyroptosis-related acute lung injury by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation","authors":"Tursunay Dilxat, Qiang Shi, Xiaofan Chen, Xuxin Liu","doi":"10.18632/aging.205721","DOIUrl":"https://doi.org/10.18632/aging.205721","url":null,"abstract":"Acute lung injury (ALI) is a major cause of acute respiratory failure with a high morbidity and mortality rate, and effective therapeutic strategies for ALI remain limited. Inflammatory response is considered crucial for the pathogenesis of ALI. Garlic, a globally used cooking spice, reportedly exhibits excellent anti-inflammatory bioactivity. However, protective effects of garlic against ALI have never been reported. This study aimed to investigate the protective effects of garlic oil (GO) supplementation on lipopolysaccharide (LPS)-induced ALI models. Hematoxylin and eosin staining, pathology scores, lung myeloperoxidase (MPO) activity measurement, lung wet/dry (W/D) ratio detection, and bronchoalveolar lavage fluid (BALF) analysis were performed to investigate ALI histopathology. Real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were conducted to evaluate the expression levels of inflammatory factors, nuclear factor-κB (NF-κB), NLRP3, pyroptosis-related proteins, and H2S-producing enzymes. GO attenuated LPS-induced pulmonary pathological changes, lung W/D ratio, MPO activity, and inflammatory cytokines in the lungs and BALF. Additionally, GO suppressed LPS-induced NF-κB activation, NLRP3 inflammasome expression, and inflammatory-related pyroptosis. Mechanistically, GO promoted increased H2S production in lung tissues by enhancing the conversion of GO-rich polysulfide compounds or by increasing the expression of H2S-producing enzymes in vivo. Inhibition of endogenous or exogenous H2S production reversed the protective effects of GO on ALI and eliminated the inhibitory effects of GO on NF-κB, NLRP3, and pyroptotic signaling pathways. Overall, these findings indicate that GO has a critical anti-inflammatory effect and protects against LPS-induced ALI by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"17 23","pages":"6521 - 6536"},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140712044","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}
NXPH4 promotes cancer proliferation and invasion. However, its specific role and mechanism in cancer remain unclear. Transcriptome and clinical data for pan-cancer were derived from the TCGA database. K-M survival curve and univariate Cox were used for prognostic analysis. CIBERSORT and TIMER algorithms were employed to calculate immune cell infiltration. Gene set enrichment analysis (GSEA) was employed for investigating the function of NXPH4. Western blot verified differential expression of NXPH4 in colon cancer. Functional assays (CCK-8, plate clonogenicity assay, wound healing assay, and Transwell assay) confirmed the impact of NXPH4 on proliferation, invasion, and migration of colon cancer cells. Dysregulation of NXPH4 in pan-cancer suggests its potential as a diagnostic and prognostic marker for certain cancers, including colon and liver cancer. High expression of NXPH4 in pan-cancer might be associated with the increase in copy number and hypomethylation. NXPH4 expression in pan-cancer is substantially linked to immune cell infiltration in the immune microenvironment. NXPH4 expression is associated with the susceptibility to immunotherapy and chemotherapy. Western blot further confirmed the higher expression of NXPH4 in colon cancer. Knockdown of NXPH4 significantly suppresses proliferation, invasion, and migration of colon cancer cell lines HT-29 and HCT116, as validated by functional assays.
{"title":"NXPH4 can be used as a biomarker for pan-cancer and promotes colon cancer progression","authors":"Zhipeng Zhang, Pengfei Wang, Siwen Chen, Dezhi Xiang, Jinzhen Chen, Wanchang Huang, Xiao Liu, Tongwen Yi, Dawei Wang, Yunfei Pu, Longfu He, Hao Zhang","doi":"10.18632/aging.205648","DOIUrl":"https://doi.org/10.18632/aging.205648","url":null,"abstract":"NXPH4 promotes cancer proliferation and invasion. However, its specific role and mechanism in cancer remain unclear. Transcriptome and clinical data for pan-cancer were derived from the TCGA database. K-M survival curve and univariate Cox were used for prognostic analysis. CIBERSORT and TIMER algorithms were employed to calculate immune cell infiltration. Gene set enrichment analysis (GSEA) was employed for investigating the function of NXPH4. Western blot verified differential expression of NXPH4 in colon cancer. Functional assays (CCK-8, plate clonogenicity assay, wound healing assay, and Transwell assay) confirmed the impact of NXPH4 on proliferation, invasion, and migration of colon cancer cells. Dysregulation of NXPH4 in pan-cancer suggests its potential as a diagnostic and prognostic marker for certain cancers, including colon and liver cancer. High expression of NXPH4 in pan-cancer might be associated with the increase in copy number and hypomethylation. NXPH4 expression in pan-cancer is substantially linked to immune cell infiltration in the immune microenvironment. NXPH4 expression is associated with the susceptibility to immunotherapy and chemotherapy. Western blot further confirmed the higher expression of NXPH4 in colon cancer. Knockdown of NXPH4 significantly suppresses proliferation, invasion, and migration of colon cancer cell lines HT-29 and HCT116, as validated by functional assays.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"4 7","pages":"5866 - 5886"},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140710789","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}
J. Rutkowsky, Zabrisky Roland, Anthony Valenzuela, An B Nguyen, Heui Hye Park, Natalie Six, Ilknur Dursun, Kyoungmi Kim, Pamela J Lein, Jon J Ramsey
Studies suggest that ketogenic diets (KD) may improve memory in mouse models of aging and Alzheimer’s disease (AD). This study determined whether a continuous or intermittent KD (IKD) enhanced cognitive behavior in the TgF344-AD rat model of AD. At 6 months-old, TgF344-AD and wild-type (WT) littermates were placed on a control (CD), KD, or IKD (morning CD and afternoon KD) provided as two meals per day for 2 or 6 months. Cognitive and motor behavior and circulating β-hydroxybutyrate (BHB), AD biomarkers and blood lipids were assessed. Animals on a KD diet had elevated circulating BHB, with IKD levels intermediate to CD and KD. TgF344-AD rats displayed impaired spatial learning memory in the Barnes maze at 8 and 12 months of age and impaired motor coordination at 12 months of age. Neither KD nor IKD improved performance compared to CD. At 12 months of age, TgF344-AD animals had elevated blood lipids. IKD reduced lipids to WT levels with KD further reducing cholesterol below WT levels. This study shows that at 8 or 12 months of age, KD or IKD intervention did not improve measures of cognitive or motor behavior in TgF344-AD rats; however, both IKD and KD positively impacted circulating lipids.
{"title":"The impact of continuous and intermittent ketogenic diets on cognitive behavior, motor function, and blood lipids in TgF344-AD rats","authors":"J. Rutkowsky, Zabrisky Roland, Anthony Valenzuela, An B Nguyen, Heui Hye Park, Natalie Six, Ilknur Dursun, Kyoungmi Kim, Pamela J Lein, Jon J Ramsey","doi":"10.18632/aging.205741","DOIUrl":"https://doi.org/10.18632/aging.205741","url":null,"abstract":"Studies suggest that ketogenic diets (KD) may improve memory in mouse models of aging and Alzheimer’s disease (AD). This study determined whether a continuous or intermittent KD (IKD) enhanced cognitive behavior in the TgF344-AD rat model of AD. At 6 months-old, TgF344-AD and wild-type (WT) littermates were placed on a control (CD), KD, or IKD (morning CD and afternoon KD) provided as two meals per day for 2 or 6 months. Cognitive and motor behavior and circulating β-hydroxybutyrate (BHB), AD biomarkers and blood lipids were assessed. Animals on a KD diet had elevated circulating BHB, with IKD levels intermediate to CD and KD. TgF344-AD rats displayed impaired spatial learning memory in the Barnes maze at 8 and 12 months of age and impaired motor coordination at 12 months of age. Neither KD nor IKD improved performance compared to CD. At 12 months of age, TgF344-AD animals had elevated blood lipids. IKD reduced lipids to WT levels with KD further reducing cholesterol below WT levels. This study shows that at 8 or 12 months of age, KD or IKD intervention did not improve measures of cognitive or motor behavior in TgF344-AD rats; however, both IKD and KD positively impacted circulating lipids.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"123 21","pages":"5811 - 5828"},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140708849","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}
Ziqi Zhao, Meichen Liu, Zhikun Lin, Mengru Zhu, Linlin Lv, Xinqing Zhu, Rui Fan, Abdullah Al-danakh, Hui He, Guang Tan
Ubiquitination of the proteins is crucial for governing protein degradation and regulating fundamental cellular processes. Deubiquitinases (DUBs) have emerged as significant regulators of multiple pathways associated with cancer and other diseases, owing to their capacity to remove ubiquitin from target substrates and modulate signaling. Consequently, they represent potential therapeutic targets for cancer and other life-threatening conditions. USP43 belongs to the DUBs family involved in cancer development and progression. This review aims to provide a comprehensive overview of the existing scientific evidence implicating USP43 in cancer development. Additionally, it will investigate potential small-molecule inhibitors that target DUBs that may have the capability to function as anti-cancer medicines.
{"title":"The mechanism of USP43 in the development of tumor: a literature review","authors":"Ziqi Zhao, Meichen Liu, Zhikun Lin, Mengru Zhu, Linlin Lv, Xinqing Zhu, Rui Fan, Abdullah Al-danakh, Hui He, Guang Tan","doi":"10.18632/aging.205731","DOIUrl":"https://doi.org/10.18632/aging.205731","url":null,"abstract":"Ubiquitination of the proteins is crucial for governing protein degradation and regulating fundamental cellular processes. Deubiquitinases (DUBs) have emerged as significant regulators of multiple pathways associated with cancer and other diseases, owing to their capacity to remove ubiquitin from target substrates and modulate signaling. Consequently, they represent potential therapeutic targets for cancer and other life-threatening conditions. USP43 belongs to the DUBs family involved in cancer development and progression. This review aims to provide a comprehensive overview of the existing scientific evidence implicating USP43 in cancer development. Additionally, it will investigate potential small-molecule inhibitors that target DUBs that may have the capability to function as anti-cancer medicines.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"41 31","pages":"6613 - 6626"},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140728136","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}
Zhong-Ning Cui, Hongzhi Li, Chunli Liu, Juan Wang, Chunguang Chen, Shanlei Hu, Xiaoli Zhao, Guangming Li
Background: The treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) have been a major medical challenge. Unraveling the landscape of tumor immune infiltrating cells (TIICs) in the immune microenvironment of HCC is of great significance to probe the molecular mechanisms. Methods: Based on single-cell data of HCC, the cell landscape was revealed from the perspective of TIICs. Special cell subpopulations were determined by the expression levels of marker genes. Differential expression analysis was conducted. The activity of each subpopulation was determined based on the highly expressed genes. CTLA4+ T-cell subpopulations affecting the prognosis of HCC were determined based on survival analysis. A single-cell regulatory network inference and clustering analysis was also performed to determine the transcription factor regulatory networks in the CTLA4+ T cell subpopulations. Results: 10 cell types were identified and NK cells and T cells showed high abundance in tumor tissues. Two NK cells subpopulations were present, FGFBP2+ NK cells, B3GNT7+ NK cells. Four T cells subpopulations were present, LAG3+ T cells, CTLA4+ T cells, RCAN3+ T cells, and HPGDS+ Th2 cells. FGFBP2+ NK cells, and CTLA4+ T cells were the exhaustive subpopulation. High CTLA4+ T cells contributed to poor prognostic outcomes and promoted tumor progression. Finally, a network of transcription factors regulated by NR3C1, STAT1, and STAT3, which were activated, was present in CTLA4+ T cells. Conclusion: CTLA4+ T cell subsets in HCC exhibited functional exhaustion characteristics that probably inhibited T cell function through a transcription factor network dominated by NR3C1, STAT1, and STAT3.
背景：晚期肝细胞癌（HCC）患者的治疗和预后一直是医学界的一大难题。揭示肿瘤免疫浸润细胞（TIICs）在 HCC 免疫微环境中的分布对探究其分子机制具有重要意义。研究方法基于 HCC 的单细胞数据，从 TIICs 的角度揭示细胞格局。通过标记基因的表达水平确定特殊细胞亚群。进行了差异表达分析。根据高表达基因确定每个亚群的活性。根据生存分析确定了影响 HCC 预后的 CTLA4+ T 细胞亚群。还进行了单细胞调控网络推断和聚类分析，以确定 CTLA4+ T 细胞亚群中的转录因子调控网络。结果发现共鉴定出 10 种细胞类型，NK 细胞和 T 细胞在肿瘤组织中含量较高。存在两种 NK 细胞亚群：FGFBP2+ NK 细胞和 B3GNT7+ NK 细胞。存在四个 T 细胞亚群：LAG3+ T 细胞、CTLA4+ T 细胞、RCAN3+ T 细胞和 HPGDS+ Th2 细胞。FGFBP2+ NK细胞和CTLA4+ T细胞是详尽的亚群。高 CTLA4+ T 细胞导致预后不良，并促进肿瘤进展。最后，CTLA4+ T细胞中存在一个由NR3C1、STAT1和STAT3调控的转录因子网络，这些转录因子被激活。结论HCC中的CTLA4+ T细胞亚群表现出功能衰竭特征，可能通过NR3C1、STAT1和STAT3主导的转录因子网络抑制T细胞功能。
{"title":"Single-cell data revealed exhaustion of characteristic NK cell subpopulations and T cell subpopulations in hepatocellular carcinoma","authors":"Zhong-Ning Cui, Hongzhi Li, Chunli Liu, Juan Wang, Chunguang Chen, Shanlei Hu, Xiaoli Zhao, Guangming Li","doi":"10.18632/aging.205723","DOIUrl":"https://doi.org/10.18632/aging.205723","url":null,"abstract":"Background: The treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) have been a major medical challenge. Unraveling the landscape of tumor immune infiltrating cells (TIICs) in the immune microenvironment of HCC is of great significance to probe the molecular mechanisms. Methods: Based on single-cell data of HCC, the cell landscape was revealed from the perspective of TIICs. Special cell subpopulations were determined by the expression levels of marker genes. Differential expression analysis was conducted. The activity of each subpopulation was determined based on the highly expressed genes. CTLA4+ T-cell subpopulations affecting the prognosis of HCC were determined based on survival analysis. A single-cell regulatory network inference and clustering analysis was also performed to determine the transcription factor regulatory networks in the CTLA4+ T cell subpopulations. Results: 10 cell types were identified and NK cells and T cells showed high abundance in tumor tissues. Two NK cells subpopulations were present, FGFBP2+ NK cells, B3GNT7+ NK cells. Four T cells subpopulations were present, LAG3+ T cells, CTLA4+ T cells, RCAN3+ T cells, and HPGDS+ Th2 cells. FGFBP2+ NK cells, and CTLA4+ T cells were the exhaustive subpopulation. High CTLA4+ T cells contributed to poor prognostic outcomes and promoted tumor progression. Finally, a network of transcription factors regulated by NR3C1, STAT1, and STAT3, which were activated, was present in CTLA4+ T cells. Conclusion: CTLA4+ T cell subsets in HCC exhibited functional exhaustion characteristics that probably inhibited T cell function through a transcription factor network dominated by NR3C1, STAT1, and STAT3.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"3 11","pages":"6550 - 6565"},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140735983","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}
Background: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. Results: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-β promoted cytostasis and partial epithelial–mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-β activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFβ-Smad signaling induced growth inhibition and partial EMT, whereas TGFβ-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-β was mutually restricted in LPCs. Mechanistically, we found that TGF-β activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFβ-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-β-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-β-induced cytostasis and partial EMT. Conclusion: These results suggested that TGF-β downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-β under fibrotic conditions and maintain partial EMT and progenitor phenotypes.
{"title":"TGF-β downstream of Smad3 and MAPK signaling antagonistically regulate the viability and partial epithelial–mesenchymal transition of liver progenitor cells","authors":"Yi-min Sun, Yu Wu, Gan-xun Li, Hui-Fang Liang, Tu-Ying Yong, Zifu Li, Bixiang Zhang, Xiao-Ping Chen, Guan-nan Jin, Ze-Yang Ding","doi":"10.18632/aging.205725","DOIUrl":"https://doi.org/10.18632/aging.205725","url":null,"abstract":"Background: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. Results: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-β promoted cytostasis and partial epithelial–mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-β activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFβ-Smad signaling induced growth inhibition and partial EMT, whereas TGFβ-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-β was mutually restricted in LPCs. Mechanistically, we found that TGF-β activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFβ-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-β-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-β-induced cytostasis and partial EMT. Conclusion: These results suggested that TGF-β downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-β under fibrotic conditions and maintain partial EMT and progenitor phenotypes.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"29 6","pages":"6588 - 6612"},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140738347","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}
Zhong-Ning Cui, Ge Li, Yanbin Shi, Xiaoli Zhao, Juan Wang, Shanlei Hu, Chunguang Chen, Guangming Li
Background: Complex cellular signaling network in the tumor microenvironment (TME) could serve as an indicator for the prognostic classification of hepatocellular carcinoma (HCC) patients. Methods: Univariate Cox regression analysis was performed to screen prognosis-related TME-related genes (TRGs), based on which HCC samples were clustered by running non-negative matrix factorization (NMF) algorithm. Furthermore, the correlation between different molecular HCC subtypes and immune cell infiltration level was analyzed. Finally, a risk score (RS) model was established by LASSO and Cox regression analyses (CRA) using these TRGs. Functional enrichment analysis was performed using gene set enrichment analysis (GSEA). Results: HCC patients were divided into three molecular subtypes (C1, C2, and C3) based on 704 prognosis-related TRGs. HCC subtype C1 had significantly better OS than C2 and C3. We selected 13 TRGs to construct the RS model. Univariate and multivariate CRA showed that the RS could independently predict patients’ prognosis. A nomogram integrating the RS and clinicopathologic features of the patients was further created. We also validated the reliability of the model according to the area under the receiver operating characteristic (ROC) curve value, concordance index (C-index), and decision curve analysis. The current findings demonstrated that the RS was significantly correlated with CD8+ T cells, monocytic lineage, and myeloid dendritic cells. Conclusion: This study provided TRGs to help classify patients with HCC and predict their prognoses, contributing to personalized treatments for patients with HCC.
{"title":"A prognostic signature established based on genes related to tumor microenvironment for patients with hepatocellular carcinoma","authors":"Zhong-Ning Cui, Ge Li, Yanbin Shi, Xiaoli Zhao, Juan Wang, Shanlei Hu, Chunguang Chen, Guangming Li","doi":"10.18632/aging.205722","DOIUrl":"https://doi.org/10.18632/aging.205722","url":null,"abstract":"Background: Complex cellular signaling network in the tumor microenvironment (TME) could serve as an indicator for the prognostic classification of hepatocellular carcinoma (HCC) patients. Methods: Univariate Cox regression analysis was performed to screen prognosis-related TME-related genes (TRGs), based on which HCC samples were clustered by running non-negative matrix factorization (NMF) algorithm. Furthermore, the correlation between different molecular HCC subtypes and immune cell infiltration level was analyzed. Finally, a risk score (RS) model was established by LASSO and Cox regression analyses (CRA) using these TRGs. Functional enrichment analysis was performed using gene set enrichment analysis (GSEA). Results: HCC patients were divided into three molecular subtypes (C1, C2, and C3) based on 704 prognosis-related TRGs. HCC subtype C1 had significantly better OS than C2 and C3. We selected 13 TRGs to construct the RS model. Univariate and multivariate CRA showed that the RS could independently predict patients’ prognosis. A nomogram integrating the RS and clinicopathologic features of the patients was further created. We also validated the reliability of the model according to the area under the receiver operating characteristic (ROC) curve value, concordance index (C-index), and decision curve analysis. The current findings demonstrated that the RS was significantly correlated with CD8+ T cells, monocytic lineage, and myeloid dendritic cells. Conclusion: This study provided TRGs to help classify patients with HCC and predict their prognoses, contributing to personalized treatments for patients with HCC.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"14 6","pages":"6537 - 6549"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140741809","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：