{"title":"In Silico and In Vitro Verification of the Effects of Chemotherapeutic Doxorubicin and 5-Fluorouracil in Combination With Curcumin and Vitamin C on MCF-7 Cells.","authors":"Aslı Akyüz, Duygu Yaşar Şirin","doi":"10.1002/jcb.30688","DOIUrl":"https://doi.org/10.1002/jcb.30688","url":null,"abstract":"<p><p>Breast cancer ranks among the most prevalent cancers. Enhancing the effectiveness of chemotherapy and patient survival is the objective of many studies. In the literature, no study has investigated the combined effect of vitamin c and curcumin with chemotherapy drugs on cell viability in the MCF-7 cell line, nor the mechanism of inflammation induced by cancer drugs, both in vitro and in silico. Thus, the purpose of this study was to assess the synergistic effect of curcumin and vitamin c in combination with the chemotherapy drugs 5-fluorouracil and doxorubicin. The cytokine hub genes of the Toll-like receptor pathway for the administered drugs were identified using the Cytoscape program, and docking studies were conducted via the Cb Dock2 website. In silico analyses indicated that doxorubicin and curcumin displayed comparable characteristics, achieving the highest interaction scores (-10) with marker proteins, whereas 5-fluorouracil and vitamin c showed lower interaction scores. Cell viability was evaluated through MTT analysis and AO/PI staining, while the expression of inflammation-related markers IL-6, IL-10, and TNF-α proteins determined using the ELISA method. After 24 h, the cell viability of the chemotherapeutic drugs administered in combination with curcumin decreased by up to 28%. Subsequently, applications at 48 and 72 h were performed. These results indicate that the effect of curcumin on cell viability is significant when combined with chemotherapy drugs. In the ELISA test, a 52% expression of IL-6 was noted in MCF-7 cells treated with curcumin, whereas the IL-6 level decreased to 15% in the other experimental groups. An increase was observed in the TNF-α expression with 5-fluorouracil and doxorubicin compared to the control, while a notable decrease was recorded in the applications with vitamin c and curcumin (p < 0.05). This study demonstrates that vitamin c and curcumin exhibit a synergistic effect with chemotherapeutic agents in the inflammatory system.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":" ","pages":"e30688"},"PeriodicalIF":3.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lactate-Dependent HIF1A Transcriptional Activation Exacerbates Severe Acute Pancreatitis Through the ACSL4/LPCAT3/ALOX15 Pathway Induced Ferroptosis.","authors":"Tingyuan Zhang, Xiaopei Huang, Shengnan Feng, Huanzhang Shao","doi":"10.1002/jcb.30687","DOIUrl":"https://doi.org/10.1002/jcb.30687","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is a common emergency in the digestive system, and in severe cases, it can progress to severe acute pancreatitis (SAP), with a mortality rate of up to 30%, representing a dire situation. SAP in mice was induced by l-arginine (l-Arg). HE, IHC, WB and ELISA were used to study the role and regulation of HIF1A in SAP. At the same time, QPCR, WB, CHIP-QPCR and luciferase report were used to explore the specific mechanism of HIF1A regulation of SAP in vitro. The research results indicate that following SAP induction, the pancreatic tissue of mice exhibited significant glycolytic abnormalities, accompanied by a marked upregulation of HIF1A expression. This led to apparent damage in the pancreatic tissue, lungs, and kidneys. However, in sh-HIF1A mice, the degree of these injuries was significantly alleviated, along with a reduction in the production of inflammatory factors, oxidative products, and lipid peroxidation markers. This suggests that HIF1A plays a crucial role in the inflammatory and oxidative stress processes during SAP. Further exploration revealed that the absence or overexpression of HIF1A affects SAP by inducing ferroptosis through the ACSL4/LPCAT3/ALOX15 pathway. Notably, the elevated lactate level resulting from glycolytic abnormalities further enhances the histone lactylation in the HIF1A promoter region, thereby aggravating the expression of HIF1A. Lactate-dependent HIF1A transcriptional activation exacerbates severe acute pancreatitis through the ACSL4/LPCAT3/ALOX15 pathway induced ferroptosis.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":" ","pages":"e30687"},"PeriodicalIF":3.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Snapshot of Cytokine Dynamics: A Fine Balance Between Health and Disease.","authors":"Sumit Mallick, Asim K Duttaroy, Bipasha Bose","doi":"10.1002/jcb.30680","DOIUrl":"https://doi.org/10.1002/jcb.30680","url":null,"abstract":"<p><p>Health and disease are intricately intertwined and often determined by the delicate balance of biological processes. Cytokines, a family of small signalling molecules, are pivotal in maintaining this balance, ensuring the body's immune system functions optimally. In a healthy condition, cytokines act as potent mediators of immune responses. They orchestrate the activities of immune cells, coordinating their proliferation, differentiation, and migration. This intricate role of cytokine signalling enables the body to effectively combat infections, repair damaged tissues, and regulate inflammation. However, the delicate equilibrium of cytokine production is susceptible to disruption. Excessive or abnormal cytokine levels can lead to a cascade of pathological conditions, including autoimmune diseases, chronic inflammation, infections, allergies, and even cancer. Interestingly, from the bunch of cytokines, few cytokines play an essential role in maintaining the balance between normal physiological status and diseases. In this review, we have appraised key cytokines' potential role and feedback loops in augmenting the imbalances in the body's biological functions, presenting a critical link between inflammation and disease pathology. Moreover, we have also highlighted the significance of cytokines and their molecular interplay, particularly in the recent viral pandemic COVID-19 disease. Hence, understandings regarding the interplay between viral infection and cytokine responses are essential and fascinating for developing effective therapeutic strategies.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":" ","pages":"e30680"},"PeriodicalIF":3.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effective Targeting of Colorectal Cancer Stem Cells by Inducing Differentiation Mediated by Low-Dose Vitamin C via β-Catenin Retention in the Cell Membrane.","authors":"Shanooja Shanavas, Utsav Sen, Rajkumar Banerjee, Sudheer Shenoy P, Bipasha Bose","doi":"10.1002/jcb.30686","DOIUrl":"https://doi.org/10.1002/jcb.30686","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are implicated as the underlying cause of tumor recurrence due to their refractoriness to conventional therapies. Targeting CSCs through novel approaches can hinder their survival and proliferation, potentially reducing the challenges associated with tumor relapse. Our previous study demonstrated that colorectal cancer stem cells (CR-CSCs) showed sensitivity to Vitamin C (Vit C), displaying a dose-responsive effect where low doses (2-10 µM) promoted cell proliferation while high doses induced cell death. In this study, we unraveled the mechanistic effects of low doses that, although induced proliferation, remarkably facilitated stemness reduction in HT-29 cell line-derived CR-CSCs. Our findings revealed that Vit C doses of 2 and 6 µM resulted in a reduction in stemness as evidenced by a reduced CD44<sup>+</sup> cell population, representing CR-CSCs. The key finding was the remarkable increase in the expression of β-catenin protein following low-dose Vit C treatment, despite a reduction in stemness, accompanied by a mesenchymal to epithelial transition (MET). The sequestration of upregulated β-catenin via E-cadherin to the cell membrane was identified as a mechanism for reduced stemness, MET, and differentiation of CR-CSCs. Importantly, the epithelial phenotype induced by low-dose Vit C rendered CR-CSCs sensitive to conventional treatments, enhancing chemosensitivity to Cisplatin, Paclitaxel, and 5-Fluorouracil by 60%-90%. These findings suggest that low dose Vit C could serve as an adjuvant to conventional therapeutic strategies for targeting advanced colorectal cancer by sensitizing CR-CSCs to chemotherapy and potentially reducing tumor recurrence.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":" ","pages":"e30686"},"PeriodicalIF":3.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In Silico Hybridization and Molecular Dynamics Simulations for the Identification of Candidate Human MicroRNAs for Inhibition of Virulent Proteins' Expression in Staphylococcus aureus.","authors":"Harshita Tiwari, Subhadip Saha, Monidipa Ghosh","doi":"10.1002/jcb.30684","DOIUrl":"https://doi.org/10.1002/jcb.30684","url":null,"abstract":"<p><p>Staphylococcus aureus is a major threat to human health, causing infections that range in severity from moderate to fatal. The rising rates of antibiotic resistance highlight the critical need for new therapeutic techniques to combat this infection. It has been recently discovered that microRNAs (miRNAs) are essential for cross-kingdom communication, especially when it comes to host-pathogen interactions. It has been demonstrated that these short noncoding RNAs control gene expression in the gut microbiota, maintaining homeostasis; dysbiosis in this system has been linked to several diseases, including cancer. Our research attempts to use this understanding to target specific bacterial species and prevent severe diseases. In particular, we look for putative human miRNAs that can attach to virulent bacterial proteins' mRNA and prevent them from being expressed. In-silico hybridization experiments were performed between 100 human miRNA sequences with varied expression levels in gram-positive bacterial infections and five virulence factor genes. In addition, these miRNAs' binding properties were investigated using molecular dynamics (MD) simulations. Our findings demonstrate that human miRNAs can target and inhibit the expression of bacterial virulent genes, thereby opening up new paths for developing innovative miRNA-based therapeutics. The implementation of MD simulations in our study not only improves the validity of our findings but also proposes a new method for constructing miRNA-based therapies against life-threatening bacterial infections.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":" ","pages":"e30684"},"PeriodicalIF":3.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RETRACTION to \"Adipose Tissue-Derived Stem Cells Inhibit Hypertrophic Scar (HS) Fibrosis via p38/MAPK Pathway\".","authors":"","doi":"10.1002/jcb.30689","DOIUrl":"https://doi.org/10.1002/jcb.30689","url":null,"abstract":"<p><strong>Retraction: </strong>C.-Y. Chai, J. Song, Z. Tan, I.-C. Tai, C. Zhang, and S. Sun, \"Adipose Tissue-Derived Stem Cells Inhibit Hypertrophic Scar (HS) Fibrosis via p38/MAPK Pathway,\" Journal of Cellular Biochemistry 120, no. 3 (2019): 4057-4064, https://doi.org/10.1002/jcb.27689. The above article, published online on 27 September 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, multiple image elements in Figures 1, 2, 3, and 4 were found to have been previously published by different author groups. Accordingly, the conclusions of this article are considered invalid by the editors.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":" ","pages":"e30689"},"PeriodicalIF":3.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhamed Adilović, Altijana Hromić-Jahjefendić, Lejla Mahmutović, Jasmin Šutković, Alberto Rubio-Casillas, Elrashdy M Redwan, Vladimir N Uversky
{"title":"Intrinsic Factors Behind the Long-COVID: V. Immunometabolic Disorders.","authors":"Muhamed Adilović, Altijana Hromić-Jahjefendić, Lejla Mahmutović, Jasmin Šutković, Alberto Rubio-Casillas, Elrashdy M Redwan, Vladimir N Uversky","doi":"10.1002/jcb.30683","DOIUrl":"https://doi.org/10.1002/jcb.30683","url":null,"abstract":"<p><p>The complex link between COVID-19 and immunometabolic diseases demonstrates the important interaction between metabolic dysfunction and immunological response during viral infections. Severe COVID-19, defined by a hyperinflammatory state, is greatly impacted by underlying chronic illnesses aggravating the cytokine storm caused by increased levels of Pro-inflammatory cytokines. Metabolic reprogramming, including increased glycolysis and altered mitochondrial function, promotes viral replication and stimulates inflammatory cytokine production, contributing to illness severity. Mitochondrial metabolism abnormalities, strongly linked to various systemic illnesses, worsen metabolic dysfunction during and after the pandemic, increasing cardiovascular consequences. Long COVID-19, defined by chronic inflammation and immune dysregulation, poses continuous problems, highlighting the need for comprehensive therapy solutions that address both immunological and metabolic aspects. Understanding these relationships shows promise for effectively managing COVID-19 and its long-term repercussions, which is the focus of this review paper.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":" ","pages":"e30683"},"PeriodicalIF":3.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yilei Guo, Bibimaryam Khan, Juanjuan Shi, Yongzhong Hou
{"title":"PPARδ Antagonist Inhibited CD47 Expression and Phagocytosis.","authors":"Yilei Guo, Bibimaryam Khan, Juanjuan Shi, Yongzhong Hou","doi":"10.1002/jcb.30685","DOIUrl":"https://doi.org/10.1002/jcb.30685","url":null,"abstract":"<p><p>Increasing evidence suggests that CD47 is highly expressed in multiple types of cancer, which could bind to SIRPα on macrophage, leading to inhibition of macrophage phagocytosis and promotion of tumor growth. However, the regulatory mechanism of CD47 gene expression is not completely clear. Our results indicated that colon cancer cells treated with GSK0660 drug, which is one of the PPARδ antagonists, significantly reduced CD47 gene and protein expression levels in a time and dose-dependent manner. CD47 reporter plasmid was constructed and dual-luciferase analysis was performed. The results suggest that GSK0660 treatment markedly reduced CD47 gene transcriptional activity. Moreover, co-cultured analysis showed that GSK0660 treatment increased phagocytosis. BALB/C mice implanted with CT-26 colon cancer cells were treated with GSK0660, and the results showed that GSK0660 significantly inhibited tumor growth. Moreover, the combination of CD47 monoclonal antibody with GSK0660 drug significantly inhibited tumor growth compared to GSK0660 or CD47 antibody treatment alone. These findings suggest that GSK0660 synergized with CD47 antibody to enhance antitumor immunotherapy.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":" ","pages":"e30685"},"PeriodicalIF":3.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trans-cleaving hammerhead ribozyme in specific regions can improve knockdown efficiency in vivo.","authors":"Yan Peng, Xilei Ai, Bo Peng","doi":"10.1002/jcb.30249","DOIUrl":"10.1002/jcb.30249","url":null,"abstract":"<p><p>Trans-cleaving techniques have been most enthusiastically embraced in the development of therapy for genetic diseases, particularly in the correction of monogenic recessive mutations at the messenger RNA level. However, easy degradation and poor catalytic activity in vivo remain significant obstacles to trans-cleaving of the hammerhead ribozyme. Herein, we found a novel scaffold RNA that stabilizes the ribozyme structure in trans-cleaving and promotes the knockdown efficiency of the hammerhead ribozyme in specific regions of living cells. We can give the trans-cleaving hammerhead ribozyme the ability to knock down specific genes in specific cell regions by changing different scaffolds. Therefore, our study proves the potential usefulness of the RNA knockdown strategy with high-specific trans-cleaving hammerhead ribozyme as a therapeutic approach in gene therapy.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"1 1","pages":"e30249"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44460283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Romina P Gobbini, Vanina Giselle Velardo, Clara Sokn, Ana C Liberman, Eduardo Arzt
{"title":"SUMO regulation of FKBP51 activity and the stress response.","authors":"Romina P Gobbini, Vanina Giselle Velardo, Clara Sokn, Ana C Liberman, Eduardo Arzt","doi":"10.1002/jcb.30411","DOIUrl":"10.1002/jcb.30411","url":null,"abstract":"<p><p>Glucocorticoids (GCs) actions are mostly mediated by the GC receptor (GR), a member of the nuclear receptor superfamily. Alterations of the GR activity have been associated to different diseases including mood disorders. FKBP51 is a GR chaperone that has gained much attention because it is a strong inhibitor of GR activity. FKBP51 exerts effects on many stress-related pathways and may be an important mediator of emotional behavior. Key proteins involved in the regulation of the stress response and antidepressant action are regulated by SUMOylation, a post-translational modification that has an important role in the regulation of neuronal physiology and disease. In this review, we focus on the role of SUMO-conjugation as a regulator of this pathway.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":" ","pages":"e30411"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9703963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}