IF 5.1 2区生物学

Cells Pub Date : 2024-10-18 DOI: 10.3390/cells13201732

Arkadiusz Grzeczka, Szymon Graczyk, Pawel Kordowitzki

{"title":"Pleiotropic Effects of Resveratrol on Aging-Related Cardiovascular Diseases-What Can We Learn from Research in Dogs?","authors":"Arkadiusz Grzeczka, Szymon Graczyk, Pawel Kordowitzki","doi":"10.3390/cells13201732","DOIUrl":"https://doi.org/10.3390/cells13201732","url":null,"abstract":"Resveratrol (RES) is a polyphenol with natural anti-inflammatory and antioxidant properties. It is found in abundance in plants, i.e., grapes and mulberry fruit. In addition, synthetic forms of RES exist. Since the discovery of its specific biological properties, RES has emerged as a candidate substance not only with modeling effects on the immune response but also as an important factor in preventing the onset and progression of cardiovascular disease (CVD). Previous research provided strong evidence of the effects of RES on platelets, mitochondria, cardiomyocytes, and vascular endothelial function. In addition, RES positively affects the coagulation system and vasodilatory function and improves blood flow. Not only in humans but also in veterinary medicine, cardiovascular diseases have one of the highest incidence rates. Canine and human species co-evolved and share recent evolutionary selection processes, and interestingly, numerous pathologies of companion dogs have a human counterpart. Knowledge of the impact of RES on the cardiovascular system of dogs is becoming clearer in the literature. Dogs have long been recognized as valuable animal models for the study of various human diseases as they share many physiological and genetic similarities with humans. In this review, we aim to shed light on the pleiotropic effects of resveratrol on cardiovascular health in dogs as a translational model for human cardiovascular diseases.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 20","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hymecromone Promotes Longevity and Insulin Sensitivity in Mice. 金丝桃素能促进小鼠的长寿和胰岛素敏感性。

IF 5.1 2区生物学

Cells Pub Date : 2024-10-18 DOI: 10.3390/cells13201727

Nadine Nagy, Kathryn S Czepiel, Gernot Kaber, Darko Stefanovski, Aviv Hargil, Nina Pennetzdorfer, Robert Targ, Saranya C Reghupaty, Thomas N Wight, Robert B Vernon, Rebecca L Hull-Meichle, Payton Marshall, Carlos O Medina, Hunter Martinez, Anissa Kalinowski, Rudolph D Paladini, Stavros Garantziotis, Joshua W Knowles, Paul L Bollyky

{"title":"Hymecromone Promotes Longevity and Insulin Sensitivity in Mice.","authors":"Nadine Nagy, Kathryn S Czepiel, Gernot Kaber, Darko Stefanovski, Aviv Hargil, Nina Pennetzdorfer, Robert Targ, Saranya C Reghupaty, Thomas N Wight, Robert B Vernon, Rebecca L Hull-Meichle, Payton Marshall, Carlos O Medina, Hunter Martinez, Anissa Kalinowski, Rudolph D Paladini, Stavros Garantziotis, Joshua W Knowles, Paul L Bollyky","doi":"10.3390/cells13201727","DOIUrl":"10.3390/cells13201727","url":null,"abstract":"Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-term administration of 4-MU with conventional C57BL/6J mice. We find that 4-MU extends median survival from 122 weeks (control) to 154 weeks (4-MU), an increase of 32 weeks (p < 0.0001 by Log-rank Mantel Cox test). The maximum lifespan of 4-MU treated mice increased from 159 to 194 weeks. In tandem with these effects, 4-MU enhances insulin sensitivity, a metabolic parameter known to regulate lifespan, as measured by insulin tolerance testing (ITT) as well as frequent sampling intra venous glucose tolerance tests (FSIVGTTs). We further observed that 4-MU treated mice weigh less while consuming the same amount of food, indicating that 4-MU treatment alters energy expenditure. However, we do not observe changes in tissue HA content in this model. We conclude that 4-MU promotes insulin sensitivity and longevity but that the underlying mechanism, and the contribution of HA is unclear. 4-MU, already approved in various countries for hepatobiliary conditions, is currently under investigation and clinical development as a therapy for several chronic inflammatory conditions. These data suggest that the beneficial effects of 4-MU on tissue metabolism may include effects on longevity.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 20","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circular RNA hsa_circ_0008726 Targets the hsa-miR-206-3p/KLF4 Axis to Modulate 4,4'-Methylene Diphenyl Diisocyanate-Glutathione Conjugate-Induced Chemokine Transcription in Macrophages. 环状 RNA hsa_circ_0008726 靶向 hsa-miR-206-3p/KLF4 轴，调节巨噬细胞中 4,4'-亚甲基二苯基二异氰酸酯-谷胱甘肽共轭物诱导的趋化因子转录。

IF 5.1 2区生物学

Cells Pub Date : 2024-10-18 DOI: 10.3390/cells13201725

Chen-Chung Lin, Brandon F Law, Justin M Hettick

{"title":"Circular RNA hsa_circ_0008726 Targets the hsa-miR-206-3p/KLF4 Axis to Modulate 4,4'-Methylene Diphenyl Diisocyanate-Glutathione Conjugate-Induced Chemokine Transcription in Macrophages.","authors":"Chen-Chung Lin, Brandon F Law, Justin M Hettick","doi":"10.3390/cells13201725","DOIUrl":"https://doi.org/10.3390/cells13201725","url":null,"abstract":"Exposure to 4,4'-methylene diphenyl diisocyanate (MDI) in the workplace may lead to the development of occupational asthma (OA). However, the specific mechanism(s) by which MDI induces OA are poorly understood. Previous reports have demonstrated that MDI and MDI-glutathione (GSH) conjugate exposure downregulates endogenous human/murine (hsa/mmu)-microRNA(miR)-206-3p, resulting in the activation of mmu/hsa-miR-206-3p-regulated signaling pathways in macrophages. Circular RNAs (circRNAs) regulate many important biological processes by targeting endogenous miRs; however, whether MDI/MDI-GSH exposure may influence circRNA expressions is unknown. Several circRNAs have been identified that regulate hsa-miR-206-3p. We hypothesize that MDI-GSH conjugate exposure induces endogenous circRNA(s) to regulate hsa-miR-206-3p in macrophages. The expression of candidate hsa-miR-206-3p-binding circRNAs was determined from MDI-GSH conjugate-treated differentiated THP-1 macrophages using RT-qPCR. MDI-GSH exposures induced hsa_circ_0008726 and its host gene transcript DNAJB6, whereas other circRNA(s) examined were either not detected or unchanged. RNA-induced silencing complex-immunoprecipitation (RISC-IP) experiments confirm that hsa-miR-206-3p can bind to hsa_circ_0008726. The expressions of endogenous hsa-miR-206-3p, hsa-miR-206-3p-regulated KLF4, and KLF4-activated M2 macrophage-associated markers and chemokines were up-/down-regulated by transfection of hsa_circ_0008726 siRNAs or hsa_circ_0008726 overexpression plasmid in macrophages, respectively. These results suggest MDI-GSH exposure downregulates hsa-miR-206-3p via induction of endogenous hsa_circ_0008726/DNAJB6, resulting in the upregulation of hsa-miR-206-3p-mediated regulations in macrophages.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 20","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hepatocellular-Carcinoma-Derived Organoids: Innovation in Cancer Research. 肝细胞癌衍生有机体：癌症研究的创新。

IF 5.1 2区生物学

Cells Pub Date : 2024-10-18 DOI: 10.3390/cells13201726

Carlo Airola, Maria Pallozzi, Eleonora Cesari, Lucia Cerrito, Leonardo Stella, Claudio Sette, Felice Giuliante, Antonio Gasbarrini, Francesca Romana Ponziani

{"title":"Hepatocellular-Carcinoma-Derived Organoids: Innovation in Cancer Research.","authors":"Carlo Airola, Maria Pallozzi, Eleonora Cesari, Lucia Cerrito, Leonardo Stella, Claudio Sette, Felice Giuliante, Antonio Gasbarrini, Francesca Romana Ponziani","doi":"10.3390/cells13201726","DOIUrl":"https://doi.org/10.3390/cells13201726","url":null,"abstract":"Hepatocellular carcinomas (HCCs) are highly heterogeneous malignancies. They are characterized by a peculiar tumor microenvironment and dense vascularization. The importance of signaling between immune cells, endothelial cells, and tumor cells leads to the difficult recapitulation of a reliable in vitro HCC model using the conventional two-dimensional cell cultures. The advent of three-dimensional organoid tumor technology has revolutionized our understanding of the pathogenesis and progression of several malignancies by faithfully replicating the original cancer genomic, epigenomic, and microenvironmental landscape. Organoids more closely mimic the in vivo environment and cell interactions, replicating factors such as the spatial organization of cell surface receptors and gene expression, and will probably become an important tool in the choice of therapies and the evaluation of tumor response to treatments. This review aimed to describe the ongoing and potential applications of organoids as an in vitro model for the study of HCC development, its interaction with the host's immunity, the analysis of drug sensitivity tests, and the current limits in this field.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 20","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Complement C5a Implication in Axonal Growth After Injury. 补体 C5a 对损伤后轴突生长的影响

IF 5.1 2区生物学

Cells Pub Date : 2024-10-18 DOI: 10.3390/cells13201729

Aurélie Cotten, Charlotte Jeanneau, Patrick Decherchi, Imad About

{"title":"Complement C5a Implication in Axonal Growth After Injury.","authors":"Aurélie Cotten, Charlotte Jeanneau, Patrick Decherchi, Imad About","doi":"10.3390/cells13201729","DOIUrl":"https://doi.org/10.3390/cells13201729","url":null,"abstract":"Complement C5a protein has been shown to play a major role in tissue regeneration through interaction with its receptor (C5aR) on target cells. Expression of this receptor has been reported in the nervous system which, upon injury, has no treatment to restore the lost functions. This work aimed at investigating the Complement C5a effect on axonal growth after axotomy in vitro. Primary hippocampal neurons were isolated from embryonic Wistar rats. Cell expression of C5aR mRNA was verified by RT-PCR while its membrane expression, localization, and phosphorylation were investigated by immunofluorescence. Then, the effects of C5a on injured axonal growth were investigated using a 3D-printed microfluidic device. Immunofluorescence demonstrated that the primary cultures contained only mature neurons (93%) and astrocytes (7%), but no oligodendrocytes or immature neurons. Immunofluorescence revealed a co-localization of NF-L and C5aR only in the mature neurons where C5a induced the phosphorylation of its receptor. C5a application on injured axons in the microfluidic devices significantly increased both the axonal growth speed and length. Our findings highlight a new role of C5a in regeneration demonstrating an enhancement of axonal growth after axotomy. This may provide a future therapeutic tool in the treatment of central nervous system injury.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 20","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Early-Life Respiratory Syncytial Virus (RSV) Infection Triggers Immunological Changes in Gut-Associated Lymphoid Tissues in a Sex-Dependent Manner in Adulthood. 早期呼吸道合胞病毒（RSV）感染引发成年期肠道相关淋巴组织的免疫学变化与性别有关

IF 5.1 2区生物学

Cells Pub Date : 2024-10-18 DOI: 10.3390/cells13201728

Stella Liong, Felicia Liong, Mitra Mohsenipour, Elisa L Hill-Yardin, Mark A Miles, Stavros Selemidis

{"title":"Early-Life Respiratory Syncytial Virus (RSV) Infection Triggers Immunological Changes in Gut-Associated Lymphoid Tissues in a Sex-Dependent Manner in Adulthood.","authors":"Stella Liong, Felicia Liong, Mitra Mohsenipour, Elisa L Hill-Yardin, Mark A Miles, Stavros Selemidis","doi":"10.3390/cells13201728","DOIUrl":"https://doi.org/10.3390/cells13201728","url":null,"abstract":"Severe respiratory syncytial virus (RSV) infection during early life has been linked to gut dysbiosis, which correlates with increased disease severity and a higher risk of developing asthma later in life. However, the impact of such early-life RSV infections on intestinal immunity in adulthood remains unclear. Herein, we show that RSV infection in 3-week-old mice induced persistent differential natural killer (NK) and T cell profiles within the lungs and gastrointestinal (GI) lymphoid tissues (GALT) in adulthood. Notably, male mice exhibited more pronounced RSV-induced changes in immune cell populations in both the lungs and GALT, while female mice displayed greater resilience. Importantly, early-life RSV infection was associated with the chronic downregulation of CD69-expressing T lymphocytes, particularly T regulatory cells in Peyer's patches, which could have a significant impact on T cell functionality and immune tolerance. We propose that RSV infection in early life is a trigger for the breakdown in immune tolerance at mucosal surfaces, with potential implications for airways allergic disease, food allergies, and other GI inflammatory diseases.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 20","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Mechanisms of Skatole-Induced Inflammatory Responses in Intestinal Epithelial Caco-2 Cells: Implications for Colorectal Cancer and Inflammatory Bowel Disease. 斯卡多尔诱导肠上皮 Caco-2 细胞炎症反应的分子机制：对结直肠癌和炎症性肠病的影响

IF 5.1 2区生物学

Cells Pub Date : 2024-10-18 DOI: 10.3390/cells13201730

Katsunori Ishii, Kazuma Naito, Dai Tanaka, Yoshihito Koto, Koichi Kurata, Hidehisa Shimizu

{"title":"Molecular Mechanisms of Skatole-Induced Inflammatory Responses in Intestinal Epithelial Caco-2 Cells: Implications for Colorectal Cancer and Inflammatory Bowel Disease.","authors":"Katsunori Ishii, Kazuma Naito, Dai Tanaka, Yoshihito Koto, Koichi Kurata, Hidehisa Shimizu","doi":"10.3390/cells13201730","DOIUrl":"https://doi.org/10.3390/cells13201730","url":null,"abstract":"Inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), in intestinal epithelial cells significantly contribute to inflammatory bowel disease (IBD) and colorectal cancer (CRC). Given our previous findings that TNF-α is upregulated in intestinal epithelial Caco-2 cells induced by skatole, a tryptophan-derived gut microbiota metabolite, the present study aimed to explore the relationship between skatole and IL-6, alongside TNF-α. Skatole elevated the promoter activity of IL-6 as well as TNF-α, and increased IL-6 mRNA expression and protein secretion. In addition to activating NF-κB, the NF-κB inhibitor BAY 11-7082 reduced skatole-induced cell survival and the mRNA expression of IL-6 and TNF-α. NF-κB activation was attenuated by the extracellular signal-regulated kinase (ERK) pathway inhibitor U0126 and the p38 inhibitor SB203580, but not by the c-Jun N-terminal kinase (JNK) inhibitor SP600125. U126 and SB203580 also decreased the skatole-induced increase in IL-6 expression. When skatole-induced AhR activation was inhibited by CH223191, in addition to promoting NF-κB activation, IL-6 expression was enhanced in a manner similar to that previously reported for TNF-α. Taken together, these results suggest that skatole-elicited NF-κB activation induces IL-6 and TNF-α expression, although AhR activation partially suppresses this process. The ability of skatole to increase the expression of IL-6 and TNF-α may significantly affect the development and progression of these diseases. Moreover, the balance between NF-κB and AhR activation appears to govern the skatole-induced increases in IL-6 and TNF-α expression. Therefore, the present findings provide new insights into the mechanisms linking tryptophan-derived gut microbiota metabolites with colorectal disease.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 20","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Neural Correlations of Olfactory Associative Reward Memories in Drosophila. 果蝇嗅觉联想奖励记忆的神经相关性

IF 5.1 2区生物学

Cells Pub Date : 2024-10-17 DOI: 10.3390/cells13201716

Yu-Chun Lin, Tony Wu, Chia-Lin Wu

{"title":"The Neural Correlations of Olfactory Associative Reward Memories in Drosophila.","authors":"Yu-Chun Lin, Tony Wu, Chia-Lin Wu","doi":"10.3390/cells13201716","DOIUrl":"https://doi.org/10.3390/cells13201716","url":null,"abstract":"Advancing treatment to resolve human cognitive disorders requires a comprehensive understanding of the molecular signaling pathways underlying learning and memory. While most organ systems evolved to maintain homeostasis, the brain developed the capacity to perceive and adapt to environmental stimuli through the continuous modification of interactions within a gene network functioning within a broader neural network. This distinctive characteristic enables significant neural plasticity, but complicates experimental investigations. A thorough examination of the mechanisms underlying behavioral plasticity must integrate multiple levels of biological organization, encompassing genetic pathways within individual neurons, interactions among neural networks providing feedback on gene expression, and observable phenotypic behaviors. Model organisms, such as Drosophila melanogaster, which possess more simple and manipulable nervous systems and genomes than mammals, facilitate such investigations. The evolutionary conservation of behavioral phenotypes and the associated genetics and neural systems indicates that insights gained from flies are pertinent to understanding human cognition. Rather than providing a comprehensive review of the entire field of Drosophila memory research, we focus on olfactory associative reward memories and their related neural circuitry in fly brains, with the objective of elucidating the underlying neural mechanisms, thereby advancing our understanding of brain mechanisms linked to cognitive systems.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 20","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NPS-1034 Exerts Therapeutic Efficacy in Renal Cell Carcinoma Through Multiple Targets of MET, AXL, and TNFRSF1A Signaling in a Metastatic Model. NPS-1034在转移模型中通过MET、AXL和TNFRSF1A信号的多个靶点对肾细胞癌发挥疗效

IF 5.1 2区生物学

Cells Pub Date : 2024-10-17 DOI: 10.3390/cells13201713

Ya-Chuan Chang, Chien-Te Liu, Chia-Ying Yu, Wen-Wei Sung

{"title":"NPS-1034 Exerts Therapeutic Efficacy in Renal Cell Carcinoma Through Multiple Targets of MET, AXL, and TNFRSF1A Signaling in a Metastatic Model.","authors":"Ya-Chuan Chang, Chien-Te Liu, Chia-Ying Yu, Wen-Wei Sung","doi":"10.3390/cells13201713","DOIUrl":"https://doi.org/10.3390/cells13201713","url":null,"abstract":"Renal cell carcinoma (RCC) has diverse pathological subtypes, most of which have a poor prognosis. Patients with advanced RCC require systemic therapies for disease control. Although targeted therapies and immune checkpoint inhibitors have shown therapeutic efficacy, patients eventually succumb to disease progression. Therefore, additional therapies targeting different pathways are needed to provide more therapeutic options for sequential treatment. Our study explored the biological mechanisms and therapeutic outcomes for NPS-1034, a dual MET/AXL inhibitor, in RCC, both in vivo and in vitro. Our results showed that NPS-1034 can significantly inhibit tumor proliferation and induce cancer cell apoptosis. Besides MET and AXL, known targets of NPS-1034, we identified TNFRSF1A as another target gene inhibited by NPS-1034 via antibody arrays. This was further supported by next-generation sequencing, showing that the TNF signaling pathway is one of the most significant NPS-1034-regulated pathways. Furthermore, one of the identified target genes, GADD45A, responsible for NPS-1034 anticancer properties, was significantly associated with patient survival in RCC. GADD45A expression was significantly upregulated via NPS-1034 and downregulated via TNFRSF1A overexpression. Finally, its therapeutic efficacy was demonstrated in vivo, showing that NPS-1034 significantly alleviated the tumor burden and inhibited cell proliferation in a lung metastatic animal model. In conclusion, we explored the therapeutic mechanism of NPS-1034 and found that it targets not only MET and AXL but also TNFRSF1A. In a lung metastatic animal model, we confirmed that NPS-1034 is a potential candidate for systemic therapy in RCC.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 20","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PKD2: An Important Membrane Protein in Organ Development. PKD2：器官发育过程中的重要膜蛋白

IF 5.1 2区生物学

Cells Pub Date : 2024-10-17 DOI: 10.3390/cells13201722

Shuo Wang, Yunsi Kang, Haibo Xie

引用次数: 0

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