{"title":"Platelet-Derived Growth Factor Promotes Glomerular Mesangial Cells Differentiation of Human Bone Marrow Hematopoietic Stem Cells - An In Vitro Study","authors":"Surekha Kattaru, Samundeshwari Echambadi Loganathan, Sireesha Kodavala, Chandra Sekhar Chodimella, Venkata Gurunadha Krishna Sarma Potukuchi","doi":"10.1002/jcb.70012","DOIUrl":"https://doi.org/10.1002/jcb.70012","url":null,"abstract":"<div>\u0000 \u0000 <p>Glomerular filtration function and homeostasis are largely due to the cross-talk between podocytes, endothelial cells, and mesangial cells (MCs). Any disturbance in this association causes glomerular diseases (GD). Cell-based therapies are the best option in the treatment of GD. It is contemplated that hematopoietic stem cells (HSCs) are best suited to regenerate these cells; earlier, we have shown the differentiation of HSCs into podocytes. In this study, MCs formation was initiated with retinoic acid (RA), BMP-7, and Activin A, resulting in comma-shaped intermediate mesoderm (IM) cells prominently expressing Osr1. Followed by inducing with EGF, FGF, and BMP-7, which resulted in elongated metanephric mesenchyme (MM) cells conspicuously expressing Pax2, Wt1, Foxd1, and Eya1. Finally, MM cells were induced with platelet-derived growth factor to form polygonal-shaped MCs expressing α-smooth muscle actin, desmin, CD44, and PDGFRβ. The growing MCs showed positivity to periodic acid Schiff's, and ANAE staining with a prominent expression of the Itga8 elucidating phagocytic property of MCs. These MCs showed conspicuous expression of CD133, notch-2, and telomerase, determining the quiescence nature with a 31.2% proliferation rate revealed through Ki-67 staining. The functionality of MCs was assessed by growing MCs in 5.5 and 25 mM glucose concentrations, and noticeable expression of angiotensinogen, angiotensin-I and II, angiotensin-converting enzyme, collagen-4, fibronectin, and TGFβ1 was observed in 25 mM concentration, while lowered expression of these genes was observed in 5.5 mM concentration explaining the role of MCs in regulating the filtration pressure. All these findings demonstrate that HSCs can rejuvenate the insulted glomerulus.</p>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595125","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}
Tabrez Faruqui, Aubaidah Akhtar, Farheen Showket, Mohd Jamal Dar, Yusuf Akhter
{"title":"Identification and Evaluation of IGF1R and Its Associated Proteins as Targets and Design of Novel Inhibitors for Cancer Therapy","authors":"Tabrez Faruqui, Aubaidah Akhtar, Farheen Showket, Mohd Jamal Dar, Yusuf Akhter","doi":"10.1002/jcb.70008","DOIUrl":"https://doi.org/10.1002/jcb.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>The insulin-like growth factor 1 receptor (IGF1R) is a crucial receptor tyrosine kinase involved in cellular growth, survival, and metabolism. Abnormal overexpression and activation are common in various cancers and contribute to tumor development and resistance to treatment. The STRING database was used to analyze the protein–protein interaction network of IGF1R and was visualized using Cytoscape to identify the key associated proteins. We assessed IGF1R and its associated protein expression levels across pan-cancer types and compared them to healthy controls using a TNMplot and cBioPortal. The objective of this study was to identify novel, low-toxicity inhibitors targeting the IGF1R and its associated proteins (e.g., AKT1 and EGFR) with better pharmacokinetic profiles for effective cancer treatment, including brain cancer. We screened 693 million drug-like compounds and selected the top 400 for toxicity analysis using ProTox-II, which identified 83 nontoxic candidates. These were categorized as either blood–brain barrier (BBB) permeant or impermeant. Molecular docking studies with AutoDock Vina 4.1 were performed on 17 target proteins, including IGF1R, with the top three compounds. Subsequently, molecular dynamics simulations using Desmond were conducted on the two most promising candidates: two BBB permeants and two impermeants. Our study identified six nontoxic IGF1R inhibitors and 16 other target protein inhibitors. Docking and MD simulations confirmed the potential of these compounds in targeted therapies. Notably, both BBB-permeant and -impermeant compounds in complex with the target proteins showed stability over 50 and 400 ns molecular simulation experiments, highlighting their potential in cancer therapy and suggesting the need for further in vitro and in vivo validation.</p></div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530344","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":"Correction to “Overexpression of lncRNA WWTR1-AS1 Associates With Tumor Aggressiveness and Unfavorable Survival in Head–Neck Squamous Cell Carcinoma”","authors":"","doi":"10.1002/jcb.70004","DOIUrl":"https://doi.org/10.1002/jcb.70004","url":null,"abstract":"<p>J. Li, Z. Li, Y. Wu, et al., “Overexpression of lncRNA WWTR1-AS1 Associates With Tumor Aggressiveness and Unfavorable Survival in Head–Neck Squamous Cell Carcinoma,” <i>Journal of Cellular Biochemistry</i> 120, no. 10 (2019): 18266–18277, https://doi.org/10.1002/jcb.29132.</p><p>In the published article, the representative flow cytometry plot in Figure 3C (NC Cal27) was included by mistake during figure preparation. The authors have corrected this issue by replacing this image with the correct original flow cytometry plot. The corrected Figure 3 is shown below.</p><p>The authors also found that the GAPDH blots in Figure 4D were inadvertently duplicated (Cal27 and FaDu cells treated with either control-ASO or WWTR1-AS1-ASO-393). Based on the original blots, the authors confirm that the GAPDH blot for FaDu cells is correct, while the blot for Cal27 cells has been included by mistake. The corrected Figure 4 is shown below.</p><p>The authors apologize for these errors and for any inconvenience these may have caused.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RETRACTION: MiR-101-3p Regulates the Viability of Lung Squamous Carcinoma Cells via Targeting EZH2","authors":"","doi":"10.1002/jcb.70007","DOIUrl":"https://doi.org/10.1002/jcb.70007","url":null,"abstract":"<p><b>RETRACTION:</b> Y. Hou, L. Li, Y. Ju, Y. Lu, L. Chang, and X. Xiang, “MiR-101-3p Regulates the Viability of Lung Squamous Carcinoma Cells via Targeting EZH2,” <i>Journal of Cellular Biochemistry</i> 118, no. 10 (2017): 3142-3149, https://doi.org/10.1002/jcb.25836.</p><p>The above article, published online on 14 December 2016 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, duplication of multiple image elements within Figure 3 C and 3E has been identified. Additional flaws and inconsistencies between methodology described and results presented were found. The authors were not able to provide comprehensive raw data. Accordingly, the article is retracted as the editors have lost confidence in the integrity and reliability of the full body of data presented in the article and consider its conclusions invalid.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the Impact of LRRK2 WD40 G2294R Mutation on Conformation and Dimerisation Dynamics: Insights From Molecular Dynamics Simulation","authors":"Chuancheng Wei, Choon Han Heh, Sek Peng Chin","doi":"10.1002/jcb.70011","DOIUrl":"https://doi.org/10.1002/jcb.70011","url":null,"abstract":"<div>\u0000 \u0000 <p>LRRK2 has gained prominence in treating Parkinson's disease as a potential drug target. Mutations in the WD40 domain, like G2294R, are notable for their influence on the stability and dimerisation of the LRRK2. Studies have shown that G2294R could result in the WD40 distortion and destabilised LRRK2 protein. However, the underlying mechanism remains unclear. To elucidate how the G2294R mutation in the WD40 domain affects the structural and functional conformation of LRRK2, the structure of WD40 G2294R was constructed using homology modelling, and the molecular dynamics simulations on G2294R and wild-type dimers and monomers were carried out. The results show that distortion mainly occurs in the areas of β3, L1, β5, L2, and β7. The dimerisation was enhanced through the conformational changes in the G2294R variant, while the domains show different contributions towards the dimerisation. Our study reveals the effects of G2294R on the WD40. It explores its role in dimerisation and distortion, which could contribute to developing novel WD40 inhibitors and elucidate the molecular mechanism of WD40 dimerisation-monomerisation equilibrium.</p>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481394","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}
Xiaoli Shen, Hao Zhang, Pengyin Zhang, Xuerui Zhao, Chang Liu, Jianan Ju, Aijun Liu, Song Wang
{"title":"Decoding SARS-CoV-2 Inhibition: Insights From Molecular Dynamics Simulation of Condensed Amino Thiourea Scaffold Small Molecules","authors":"Xiaoli Shen, Hao Zhang, Pengyin Zhang, Xuerui Zhao, Chang Liu, Jianan Ju, Aijun Liu, Song Wang","doi":"10.1002/jcb.70005","DOIUrl":"https://doi.org/10.1002/jcb.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>The main protease (M<sup>pro</sup>) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) plays a crucial role in viral replication. In this study, the binding modes and inhibitory mechanisms of eight condensed amino thiourea scaffold inhibitors of M<sup>pro</sup> in proteins were investigated using a combination of molecular docking, molecular dynamics simulations, and MM/PBSA binding free energy calculations. The results indicated that the para-hydroxyl group on the benzene ring at the head of the inhibitor has a decisive influence on the initial docking pose and binding free energy strength of the inhibitor. Additionally, the position and length of the hydrophobic side chain on the tail six-membered ring significantly impacted the final binding pose of the inhibitor. The presence of a long hydrophobic side chain in the ortho position of this ring, through its interaction with the P4 hydrophobic pocket, led to an opposite binding mode in the protein compared with when it was present with or without the para-side chain. Different lengths of para-substituted side chains affected the positioning of the inhibitors in the enzyme. These different binding modes led to variations in the binding free energy between the inhibitor and the protein, which in turn gave rise to differences in inhibitory capability.</p></div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475515","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":"Peroxisome Proliferator-Activated Receptor-Gamma Activation by an Active Compound in Lythrum anceps (Koehne) Makino","authors":"Ryo Miyata, Masanobu Suzuki, Yuka Okazaki, Daigo Abe, Yoshihiro Nakajima","doi":"10.1002/jcb.70009","DOIUrl":"https://doi.org/10.1002/jcb.70009","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Lythrum anceps</i> (Koehne) Makino (Japanese common name: “Misohagi”) is an edible plant belonging to the Lythraceae family. It is mainly distributed in Asia, Northern Africa, and Europe. Plants of the genus <i>Lythrum</i> exhibit a broad range of biological activities including anti-inflammatory and antimicrobial activities. Because of this, the plants are used in traditional medicine to treat hemorrhage, infected wounds, and dysentery. The activation of peroxisome proliferator-activated receptor-gamma (PPARγ) is an effective target for improving insulin resistance and anti-inflammatory activity. However, PPARγ activation by the genus <i>Lythrum</i> remains unclear. Aiming to evaluate PPARγ activation by <i>L. anceps</i>, we generated a reporter cell line using an artificial chromosome vector that stably expresses dual-color beetle luciferases. Dual-color real-time bioluminescence monitoring revealed marked PPARγ activation in <i>L. anceps</i> extracts. Moreover, ellagic acid was identified as a PPARγ activator present in <i>L. anceps</i> by a bioassay-guided fractionation approach.</p>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455911","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}
Mario Alejandro Aguilar-Chaparro, Sonia Andrea Rivera-Pineda, Hury Viridiana Hernández-Galdámez, Emmanuel Ríos-Castro, Olga Lilia Garibay-Cerdenares, Carolina Piña-Vázquez, Saúl Villa-Treviño
{"title":"Transforming Growth Factor-β Modulates Cancer Stem Cell Traits on CD44 Subpopulations in Hepatocellular Carcinoma","authors":"Mario Alejandro Aguilar-Chaparro, Sonia Andrea Rivera-Pineda, Hury Viridiana Hernández-Galdámez, Emmanuel Ríos-Castro, Olga Lilia Garibay-Cerdenares, Carolina Piña-Vázquez, Saúl Villa-Treviño","doi":"10.1002/jcb.70003","DOIUrl":"https://doi.org/10.1002/jcb.70003","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) is a formidable malignancy, with growing interest in identifying cancer stem cells (CSCs) as potential therapeutic targets. CD44 isoforms have emerged as promising CSC markers in HCC, often associated with epithelial-mesenchymal transition (EMT) induced by transforming growth factor-beta (TGF-β). However, the intricate relationship between CSC traits, CD44 isoforms, and TGF-β effects on CD44 subpopulations in HCC remains unclear. This study aimed to clarify how TGF-β influences proteomic changes and CSC traits in subpopulations expressing standard CD44 isoform (CD44std) and CD44 variant 9 (CD44v9). Treating SNU-423 cells with TGF-β lead to notable morphological changes, resembling a spindle-like phenotype, along with reductions in CD44v9+ subpopulations and differential CD44std expression. Proteomic analysis highlighted significant alterations in signaling pathways, particularly the mitogen-activated protein kinase (MAPK) pathway. Validation experiments demonstrated upregulation in CD44std cells and downregulation in CD44v9 cells post-TGF-β treatment. Furthermore, TGF-β exerted regulatory influence over Sox2 and Nanog expression, resulting in increased colony and spheroid formation in CD44std cells but decreased capabilities in CD44v9 cells. TGF-β also enhanced the migratory and invasive properties of both subpopulations through EMT, alongside increased adhesive abilities in CD44v9 cells. These findings illuminate the dynamic interplay between TGF-β and CD44std/CD44v9 subpopulations, emphasizing the role of MAPK signaling and modulation of CSC traits. This research contributes to understanding the dynamic interplay between CD44 isoforms and TGF-β in HCC.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypoxic Secretome and Exosomes Derived From Human Glioblastoma Cells (U87MG) Promote Protumorigenic Phenotype of Microglia in Vitro","authors":"Sangati Pancholi, Ritvi Shah, Utsav Bose, Ankit Yadav, Karthik Murukan, Prakash Pillai","doi":"10.1002/jcb.70002","DOIUrl":"https://doi.org/10.1002/jcb.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioblastoma multiforme (GBM), a highly heterogeneous CNS tumor known for its highest incidence rates and poor prognosis has shown limited success in the therapies due to hypoxia—driving immune-suppression in the tumor microenvironment (TME). Emerging evidence highlights the involvement of tumor cell-derived exosomes in tumor-associated microglia polarization via transfer of exosomal onco-proteins and miRNAs. Although the regulatory role of long noncoding RNAs (lncRNAs) in immune signaling are known, its mechanism in microglial polarization via exosomes in GBM still remains poorly understood. In our study, we found that in comparison to the normoxic GBM-derived exosomes lncRNA H19 was significantly upregulated in hypoxic GBM-derived exosomes. Hypoxic GBM-derived exosomes and secretome (conditioned media) caused the reduction in the % phagocytosis of microglia as compared with the control group. Moreover, GBM secretome caused increase in the M2-specific genes (IL10, STAT-3, CD163, CD206) in microglia indicating its polarization to the protumorigenic (M2) phenotype. LncRNA H19 knocked down GBM-secretome treatment in microglia further reduced the STAT-3 expression indicating H19 mediated signaling. Overall, our results suggest the involvement of hypoxic exosomes and lncRNA H19 in microglial polarization and H19 as a potential target.</p>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111512","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}
Pranit Hemant Bagde, Meenakshi Kandpal, Annu Rani, Sachin Kumar, Amit Mishra, Hem Chandra Jha
{"title":"Proteasomal Dysfunction in Cancer: Mechanistic Pathways and Targeted Therapies","authors":"Pranit Hemant Bagde, Meenakshi Kandpal, Annu Rani, Sachin Kumar, Amit Mishra, Hem Chandra Jha","doi":"10.1002/jcb.70000","DOIUrl":"10.1002/jcb.70000","url":null,"abstract":"<div>\u0000 \u0000 <p>Proteasomes are the catalytic complexes in eukaryotic cells that decide the fate of proteins involved in various cellular processes in an energy-dependent manner. The proteasomal system performs its function by selectively destroying the proteins labelled with the small protein ubiquitin. Dysfunctional proteasomal activity is allegedly involved in various clinical disorders such as cancer, neurodegenerative disorders, ageing, and so forth, making it an important therapeutic target. Notably, compared to healthy cells, cancer cells have a higher protein homeostasis requirement and a faster protein turnover rate. The ubiquitin-proteasome system (UPS) helps cancer cells increase rapidly and experience less apoptotic cell death. Therefore, understanding UPS is essential to design and discover some effective inhibitors for cancer therapy. Hereby, we have focused on the role of the 26S proteasome complex, mainly the UPS, in carcinogenesis and seeking potential therapeutic targets in treating numerous cancers.</p>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065853","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}