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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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

Difenoconazole Induced Damage of Bovine Mammary Epithelial Cells via ER Stress and Inflammatory Response. 二苯并唑通过ER应激和炎症反应诱导牛乳腺上皮细胞损伤

IF 5.1 2区生物学

Cells Pub Date : 2024-10-17 DOI: 10.3390/cells13201715

Myoung-Jun Na, Won-Young Lee, Hyun-Jung Park

{"title":"Difenoconazole Induced Damage of Bovine Mammary Epithelial Cells via ER Stress and Inflammatory Response.","authors":"Myoung-Jun Na, Won-Young Lee, Hyun-Jung Park","doi":"10.3390/cells13201715","DOIUrl":"https://doi.org/10.3390/cells13201715","url":null,"abstract":"Difenoconazole (DIF) is a fungicide used to control various fungi. It is absorbed on the surface of different plants and contributes significantly to increased crop production. However, DIF is reported to exhibit toxicity to fungi and to aquatic plants, fish, and mammals, including humans, causing adverse effects. However, research on the impact of DIF on the mammary epithelial cells of herbivorous bovines is limited. DIF-induced damage and accumulation in the mammary glands can have direct and indirect effects on humans. Therefore, we investigated the effects and mechanisms of DIF toxicity in MAC-T cells. The current study revealed that DIF reduces cell viability and proliferation while triggering apoptotic cell death through the upregulation of pro-apoptotic proteins, including cleaved caspase 3 and Bcl-2-associated X protein (BAX), and the downregulation of leukemia type 2 (BCL-2). DIF also induced endoplasmic reticulum (ER) stress by increasing the expression of genes or proteins of Bip/GRP78, protein disulfide isomerase (PDI), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and endoplasmic reticulum oxidoreductase 1 Alpha (ERO1-Lα). We demonstrated that DIF induces mitochondria-mediated apoptosis in MAC-T cells by activating ER stress pathways. This cellular damage resulted in a significant increase in the expression of inflammatory response genes and proteins, including cyclooxygenase 2 (COX2), transforming growth factor beta 3 (TGFB3), CCAAT enhancer binding protein delta (CEBPD), and iNOS, in DIF-treated groups. In addition, spheroid formation by MAC-T cells was suppressed by DIF treatment. Our findings suggest that DIF exposure in dairy cows may harm mammary gland function and health and may indirectly affect human consumption of milk.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495953","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":null,"pages":null},"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

Association Between Systemic Neuroinflammation, Pain Perception and Clinical Status in Fibromyalgia Patients: Cross-Sectional Study. 纤维肌痛患者的全身神经炎症、疼痛感觉和临床状态之间的关系：横断面研究

IF 5.1 2区生物学

Cells Pub Date : 2024-10-17 DOI: 10.3390/cells13201719

María Elena González-Álvarez, Víctor Riquelme-Aguado, Ángela González-Pérez, Rosa Murillo-Llergo, María Manjón-Olmedillas, Silvia Turroni, Giacomo Rossettini, Jorge Hugo Villafañe

{"title":"Association Between Systemic Neuroinflammation, Pain Perception and Clinical Status in Fibromyalgia Patients: Cross-Sectional Study.","authors":"María Elena González-Álvarez, Víctor Riquelme-Aguado, Ángela González-Pérez, Rosa Murillo-Llergo, María Manjón-Olmedillas, Silvia Turroni, Giacomo Rossettini, Jorge Hugo Villafañe","doi":"10.3390/cells13201719","DOIUrl":"https://doi.org/10.3390/cells13201719","url":null,"abstract":"Background: Fibromyalgia (FM) is characterized by chronic pain and a complex array of symptoms, with neuroinflammation implicated in its pathophysiology.Methods: This study aimed to explore the association between neuroinflammation, measured through interleukin levels (IL-1, IL-6, IL-8), and clinical outcomes in FM patients. Using a cross-sectional study design, blood levels of these interleukins were correlated with pain severity and disability, assessed via the Fibromyalgia Impact Questionnaire (FIQ) and pain measures.Results: Results indicated that IL-6 and IL-8 may particularly serve as biomarkers for pain severity and disability in FM patients, showing significant associations with worse clinical outcomes. Elevated IL-8 levels, for instance, correlated strongly with increased pain perception and higher disability scores.Conclusions: These findings suggest that specific interleukins are not only elevated in FM but are actively involved in the modulation of pain and disability, underscoring the role of systemic neuroinflammation in the clinical severity of FM. This study contributes to a deeper understanding of the inflammatory mechanisms in FM and underscores the potential of targeting interleukins in therapeutic strategies.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495913","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

Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes. 健康和神经退行性疾病中的脑代谢：神经元与星形胶质细胞之间的相互作用。

IF 5.1 2区生物学

Cells Pub Date : 2024-10-17 DOI: 10.3390/cells13201714

Polina Shichkova, Jay S Coggan, Henry Markram, Daniel Keller

引用次数: 0

Metabolic Reprogramming Induced by Aging Modifies the Tumor Microenvironment. 衰老诱导的代谢重编程改变了肿瘤微环境

IF 5.1 2区生物学

Cells Pub Date : 2024-10-17 DOI: 10.3390/cells13201721

Xingyu Chen, Zihan Wang, Bo Zhu, Min Deng, Jiayue Qiu, Yunwen Feng, Ning Ding, Chen Huang

{"title":"Metabolic Reprogramming Induced by Aging Modifies the Tumor Microenvironment.","authors":"Xingyu Chen, Zihan Wang, Bo Zhu, Min Deng, Jiayue Qiu, Yunwen Feng, Ning Ding, Chen Huang","doi":"10.3390/cells13201721","DOIUrl":"https://doi.org/10.3390/cells13201721","url":null,"abstract":"Aging is an important risk factor for tumorigenesis. Metabolic reprogramming is a hallmark of both aging and tumor initiation. However, the manner in which the crosstalk between aging and metabolic reprogramming affects the tumor microenvironment (TME) to promote tumorigenesis was poorly explored. We utilized a computational approach proposed by our previous work, MMP3C (Modeling Metabolic Plasticity by Pathway Pairwise Comparison), to characterize aging-related metabolic plasticity events using pan-cancer bulk RNA-seq data. Our analysis revealed a high degree of metabolically organized heterogeneity across 17 aging-related cancer types. In particular, a higher degree of several energy generation pathways, i.e., glycolysis and impaired oxidative phosphorylation, was observed in older patients. Similar phenomena were also found via single-cell RNA-seq analysis. Furthermore, those energy generation pathways were found to be weakened in activated T cells and macrophages, whereas they increased in exhausted T cells, immunosuppressive macrophages, and Tregs in older patients. It was suggested that aging-induced metabolic switches alter glucose utilization, thereby influencing immune function and resulting in the remodeling of the TME. This work offers new insights into the associations between tumor metabolism and the TME mediated by aging, linking with novel strategies for cancer therapy.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495920","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 Role of the Insular Cortex and Serotonergic System in the Modulation of Long-Lasting Nociception. 岛叶皮层和血清素能系统在调节持久痛觉中的作用

IF 5.1 2区生物学

Cells Pub Date : 2024-10-17 DOI: 10.3390/cells13201718

Ulises Coffeen, Gerardo B Ramírez-Rodríguez, Karina Simón-Arceo, Francisco Mercado, Angélica Almanza, Orlando Jaimes, Doris Parra-Vitela, Mareli Vázquez-Barreto, Francisco Pellicer

{"title":"The Role of the Insular Cortex and Serotonergic System in the Modulation of Long-Lasting Nociception.","authors":"Ulises Coffeen, Gerardo B Ramírez-Rodríguez, Karina Simón-Arceo, Francisco Mercado, Angélica Almanza, Orlando Jaimes, Doris Parra-Vitela, Mareli Vázquez-Barreto, Francisco Pellicer","doi":"10.3390/cells13201718","DOIUrl":"https://doi.org/10.3390/cells13201718","url":null,"abstract":"The insular cortex (IC) is a brain region that both receives relevant sensory information and is responsible for emotional and cognitive processes, allowing the perception of sensory information. The IC has connections with multiple sites of the pain matrix, including cortico-cortical interactions with the anterior cingulate cortex (ACC) and top-down connections with sites of descending pain inhibition. We explored the changes in the extracellular release of serotonin (5HT) and its major metabolite, 5-hydroxyindoleacetic acid (5HIAA), after inflammation was induced by carrageenan injection. Additionally, we explored the role of 5HT receptors (the 5HT1A, 5HT2A, and 5HT3 receptors) in the IC after inflammatory insult. The results showed an increase in the extracellular levels of 5HT and 5-HIAA during the inflammatory process compared to physiological levels. Additionally, the 5HT1A receptor was overexpressed. Finally, the 5HT1A, 5HT2A, and 5HT3 receptor blockade in the IC had antinociceptive effects. Our results highlight the role of serotonergic neurotransmission in long-lasting inflammatory nociception within the IC.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495968","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

Cells最新文献